د. حسين محمد جمعة اختصاصي الامراض الباطنة البورد العربي كلية طب الموصل 2009
Af.Cordaron.pericarditis myocarditis
Myocardial infarction with ST-segment elevation. Myocardial infarction without ST-segment elevation. Unstable angina. Share acommon pathophysiology: atherosclerotic plaque rupture, erosion, or both with superimposed intracoronary thrombosis, commonly known as atherothrombosis.Acute coronary syndromes
Life-threatening Intracranial bleeding or bleeding requiring surgical intervention or transfusion of a total of at least 4 units of blood or blood products, including fresh-frozen plasma. Moderate bleeding Intraocular hemorrhage or as bleeding that the treating physician determined required transfusion of 1 to 3 units of blood or blood products. All other bleeding was classified as minor.
Bleeding was categorized as
Synthetic pentasaccharide that selectively inhibits factor Xa. administered daily without laboratory monitoring. a low dose of fondaparinux (2.5 mg) had similar efficacy to higher doses. was compared with enoxaparin in 20,078 patients with acute coronary syndromes. Treatment of about 150 patients with fondaparinux rather than enoxaparin would result in three fewer bleeding events and one fewer death at 180 days.
fondaparinux
The specific anti–factor Xa activity of fondaparinux, as compared with the antithrombin and anti–factor Xa effect of enoxaparin, may in part be responsible for its safer profile. Fondaparinux inhibits factor Xa within the clot, preventing thrombus progression and thus enhancing effectiveness, but does not inhibit platelet function, thus enhancing safety.
Patients with stable heart disease make up about three-quarters of all the patients who undergo angioplasty and receive stents in the United States "What the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial tells us is that optimal medical [drug] therapy, when combined with lifestyle changes, appears to be the equal of angioplasty and optimal medical therapy combined.
Treatments are designed to make people feel better or live longer. (PCI) is effective at reducing angina in patients with symptomatic coronary artery disease and at reducing mortality in patients who have acute myocardial infarction with ST-segment elevation and in those who have high-risk acute coronary syndromes without ST-segment elevation. With the increasing availability of noninvasive imaging of coronary artery disease, asymptomatic patients are often referred for PCI
(COURAGE) trial provide some answers to these questions. They report that for a large population with stable coronary artery disease, the 4.6-year cumulative rates of myocardial infarction and death were 19.0% in patients who underwent PCI in addition to receiving optimal medical therapy (PCI group) and 18.5% in those who received medical therapy alone (medical-therapy group) the rates of death were approximately 8% in both study groups.
COURAGE group randomly assigned almost 2,300 patients with stable but significant heart disease to one of two treatment regimens at 50 U.S. and Canadian treatment centers. The first group received drug therapy alone, while the second group received the drug therapy plus angioplasty. During a follow-up from two to seven years. There were also no significant differences between patients who had angioplasty and those who had drug therapy alone in rates of death, heart attack, stroke or hospitalization for acute coronary syndrome (20.0 percent vs. 19.5 percent) or heart attack alone (13.2 percent vs. 12.3 percent( The only benefit of angioplasty, according to Boden's team, was that it reduced chest pain over the long-term compared with drug therapy alone..
Balloon inflation and stent deployment injures the endothelial layer of the vessel wall. Endothelial recovery takes about four weeks with bare metal stents, but it can take several months with drug eluting stents because of bystander eluted drug inhibition. The risk of stent thrombosis may therefore increase because of prolonged exposure to the stent strut. Stent thrombosis may occur later with drug eluting stents than with bare metal stents, potentially many months after the procedure. Though this happens in only about 2% of patients, up to half of these may die or have acute myocardial infarction.
To reduce the risk of stent thrombosis, patients are given dual antiplatelet therapy with aspirin and clopidogrel. With bare metal stents patients take aspirin for life, while clopidogrel is needed to cover the one month period of endothelial regrowth only. The duration of clopidogrel therapy is difficult to determine for drug eluting stents, however, as it is unclear how long endothelial healing takes.
At this time, FDA believes that coronary DES remain safe and effective when used in patients having clinical and coronary anatomic features similar to those treated in the pivotal trials conducted by the manufacturers for FDA approval.
The approved indications are:Sirolimus -eluting Coronary Stent is indicated for improving coronary luminal diameter in patients with symptomatic ischemic disease due to discrete de novo lesions of length ≤ 30 mm in native coronary arteries with reference vessel diameter of ≥2.5 mm to ≤3.5 mm.Paclitaxel -Eluting Coronary Stent System is indicated for improving luminal diameter for the treatment of de novo lesions ≤28 mm in length in native coronary arteries ≥2.5 to ≤3.75 mm in diameter.
At this time, FDA believes that coronary drug-eluting stents remain safe and effective when used for the FDA-approved indications. These devices have significantly reduced the need for a second surgery to treat restenosis for thousands of patients each year.
About 30 percent of the patients who received drug therapy alone did eventually undergo angioplasty because their symptoms couldn't be managed with drugs alone. In addition, about 21 percent of the patients who received stents needed to have another procedure, Boden said, As an initial strategy, medical therapy is a defendable approach," Boden added. "We should no longer consider it to be putting patients in harm's way, or thinking of it as an inferior treatment strategy.
Angioplasty should be reserved for patients who have continuing symptoms, Hochman said. "If you have too much angina to do the activities you want to do, despite a trial of intensive medical therapy, then angioplasty is a good option," she said, (professor of cardiology at New York University School of Medicine.(
A meta-analysis compared stenting with minimally invasive CABG of the left anterior descending artery. Stenting was associated with a higher rate of recurrent angina a higher incidence of major cerebral and coronary events and greater need for repeat coronary revascularization. Mortality was similar with the two approaches. A cost-effectiveness analysis using the same data showed stenting to be more cost-effective in the first 2 years, but by 5 years CABG was more cost-effective.
Randomised trials have shown that drug eluting stents, which are coated with agents such as sirolimus or paclitaxel that inhibit such local smooth muscle proliferation, reduce the need for repeat procedures to about 5%.
the British Cardiovascular Interventional Society has recently recommended that dual antiplatelet therapy should be continued for one year in all patients having drug eluting stents inserted.
continued research into developing drug eluting stents that allow more rapid endothelial regrowth will reduce the need for prolonged dual antiplatelet therapy. In the meantime, we recommend that the excess risk of stent thrombosis (up to 0.3% each year) balanced against a 60-70% reduction in the need for a repeat procedure with drug eluting stents compared with bare metal stents should be used as the basis for informed consent.
factors most predictive of adverse outcome were : comorbidity, diabetes, shorter duration of symptoms, increasing severity of symptoms, abnormal ventricular function, resting electrocardiogaphic changes. The annual incidence of death in the survey was 1.5%, and the incidence of non-fatal myocardial infarction was 1.4%.
Secondary prevention for patients after a myocardial infarction: summary of NICE guidance
The size of the infarction is a major determinant of both the risk of death and the likelihood of subsequent heart failure. For this reason, a goal of therapy is to reduce the size of the infarct. CRP is an acute-phase serum protein that is synthesized by hepatocytes. During infection, inflammation, and tissue injury, the serum level of CRP rises by a factor of up to several thousand. Pepys et al. recently reported that they used a small molecule that binds and inhibits human C-reactive protein (CRP) to reduce the size of myocardial infarctions. designed a small molecule,
1,6-bis(phosphocholine)-hexane (abbreviated Bis(PC)-H), that binds CRP and prevents interactions between CRP and its various ligands, as well as CRP-induced complement activation.
Necrosis of viable myocardium predominantly occurs between 30 to 90 minutes after coronary artery occlusion. This has formed the basis of "the golden hour" during which prompt reperfusion strategies (thrombolysis or primary angioplasty) prevent extensive myocardial necrosis that leads to left ventricular dysfunction and worse prognosis. Even before angioplasty, thrombolysis within the first hour cut deaths by half.
Treat all patients with the following combination: 1. Angiotensin converting enzyme inhibitor (reduces mortality, the risk of myocardial infarction, and, in selected patients, the risk of developing heart failure) 2. Aspirin (reduces cardiovascular mortality and morbidity) 3. B-blocker (reduces total mortality and cardiovascular morbidity). 4. Statin (reduces total mortality and cardiovascular morbidity).
5. After a non-ST elevation myocardial infarction , treat patients with both clopidogrel and low dose aspirin for 12 months. (reduces cardiovascular mortality and the risk of myocardial infarction and stroke). 6. After an ST elevation myocardial infarction , treat patients for at least four weeks if this combination has been started within the first 24 hours (reduces total mortality and the risk of myocardial infarction and stroke). Thereafter, continue standard treatment, including low dose aspirin without clopidogrel, unless there are other indications to continue both.
In patients intolerant of both aspirin and clopidogrel, consider treatment with moderate intensity warfarin (aiming for an international normalised ratio of 2-3) instead (reduces the risk of myocardial infarction). In patients intolerant of clopidogrel and who have a low risk of bleeding, consider treatment with aspirin and moderate intensity warfarin combined. In patients already taking warfarin for another indication, continue warfarin; in those taking moderate intensity warfarin (international normalised ratio of 2-3) and who have a low risk of bleeding, consider adding aspirin.
Lifestyle Advise patients: To take enough regular physical activity to increase exercise capacity (reduces total mortality), building this up to 20-30 minutes a day to the point of slight breathlessness To quit smoking. To eat a Mediterranean-style diet: more bread, fruit, vegetables, and fish; less meat; inclusion of products based on vegetable and plant oils rather than butter and cheese (reduces total mortality and the risk of myocardial infarction( To consume at least 7 g of omega 3 fatty acids a week.
5. To keep weekly alcohol consumption within safe limits no more than 21 units a week for men, 14 units for women and to avoid binge drinking (more than three drinks in 1-2 hours( 6. To achieve and maintain a healthy weight if overweight or obese.
Advise patients against taking: Supplements containing carotene (may increase risk of cardiovascular death (. Vitamin E or C supplements (no evidence of benefit(. Folic acid supplements (no evidence of benefit(.
Include : exercise (reduces total mortality), health education, and stress management (reduces anxiety, depression and the risk of non-fatal myocardial infarction Comprehensive cardiac rehabilitation may be offered as a validated home based programme (for example, the Edinburgh Heart Manual( with follow-up by a trained facilitator. Include advice on return to work and to activities of daily living, taking into account the patient's physical and psychological status, the nature of the activity or work proposed and the work environment. Reassure patients that after recovery from a heart attack, sexual activity presents no greater risk of triggering a subsequent attack.
How long should patients with ST elevation myocardial infarction who have been treated with thrombolysis take aspirin plus clopidogrel, compared with aspirin alone? How effective is long term continuation of drugs for secondary prevention after a myocardial infarction? For example, do all patients with normal left ventricular function benefit from long term treatment with blockers and angiotensin converting enzyme inhibitors? How effective is spironolactone compared with eplerenone in patients with heart failure and left ventricular dysfunction early after myocardial infarction?
4. What strategies are effective in improving uptake of and adherence to comprehensive cardiac rehabilitation programmes, particularly in groups under-represented in those programmes? 5. What is the added value of the non-exercise components of comprehensive cardiac rehabilitation programmes? 6. How effective are omega 3 acid ethyl esters in all patients after myocardial infarction? 7. What measures encourage the maintenance of regular exercise and a Mediterranean style diet beyond the period of comprehensive cardiac rehabilitation?
Treat patients with heart failure and left ventricular systolic dysfunction with an aldosterone antagonist licensed for this indication, preferably after treatment with an angiotensin converting enzyme inhibitor, within three to 14 days of the acute myocardial infarction (reduces total mortality and the risk of hospital admission for cardiovascular events, including heart failure).
In the days or weeks after a myocardial infarct, around 30–40% of patients have major LVSD ( [LVEF] of 40% or less), of whom at least half develop transient or persistent clinical features of heart failure. Another 20% of patients develop heart failure without LVSD. Both LVSD and heart failure (even if transient) independently increase the risk of cardiac death in the days and months following myocardial infarction: heart failure alone increases the risk by 2–6-fold; LVSD and heart failure together increase the risk 8-fold (from 3% to 26% in one study).
The hormone aldosterone has an important role in the pathophysiology of heart failure. Its actions lead to the retention of sodium and the loss of magnesium and potassium, and may contribute to sympathetic activation, parasympathetic inhibition, and myocardial and vascular fibrosis. Blocking the effects of aldosterone with spironolactone benefits patients with severe heart failure
In a double-blind randomised placebo-controlled trial, involving 1,663 patients with severe heart failure and LVEF of 35% or less who were on ACE inhibitor (if tolerated) and loop diuretic therapy, fewer of those who also received spironolactone 25mg daily died (35% vs. 46% with placebo, p<0.001; number needed to treat [NNT] for 24 months to prevent 1 death = 9), mainly because of fewer deaths from progressive heart failure or sudden cardiac death ,Spironolactone can cause hyperkalaemia. It also blocks androgen receptors and is an agonist at progesterone receptors, effects that can lead to problems such as gynaecomastia, impotence, decreased libido and menstrual irregularities. In the trial described above, gynaecomastia or breast pain was reported by 10% of men on spironolactone .
is the 9 , 11 -epoxy derivative of mexrenone, an aldosterone-receptor antagonist similar to spironolactone. The mexrenone molecule was modified with the aim of reducing the likelihood of the unwanted effects characteristic of spironolactone. Eplerenone is 40-fold less potent than spironolactone at blocking aldosterone activation of human mineralocorticoid receptors and 370-fold less potent at blocking androgen receptors, and has no activity at progesterone receptors .
Eplerenone
Eplerenone is indicated for use "in addition to standard therapy including beta-blockers, to reduce the risk of cardiovascular mortality and morbidity in stable patients with left ventricular dysfunction (LVEF 40%) and clinical evidence of heart failure after recent myocardial infarction". It should be started at a dose of 25mg once daily usually within 3–14 days of an acute myocardial infarct, and the dose increased to 50mg once daily, preferably within 4 weeks, reducing the dose to 25mg if the serum potassium concentration rises above 5.4mmol/L and stopping the drug if the potassium concentration reaches 6.0mmol/L.
Eplerenone should not be started in patients with a serum potassium concentration above 5mmol/L, creatinine clearance below 50mL/min or severely impaired liver function, or in those taking potassium supplements or potassium-sparing diuretics. Eplerenone is primarily metabolised via cytochrome P450 isoenzymeCYP 3A4, and so patients taking "strong" inhibitors of this isoenzyme (e.g. itraconazole, ritonavir, clarithromycin) should not be started on eplerenone. For patients taking mild–moderate inhibitors (e.g. erythromycin, diltiazem, verapamil, fluconazole), the dose of eplerenone should not exceed 25mg daily.
The SPC recommends avoiding co-administration of eplerenone with lithium (because of the potential for lithium toxicity), and ciclosporin and tacrolimus (which can lead to impaired renal function and hyperkalemia). The SPC advises that serum potassium should be measured before starting eplerenone therapy, within the first week of, and 1 month after, starting treatment or adjusting the dose, and should be assessed "as needed periodically thereafter".6 It also recommends "frequent and regular" monitoring of serum potassium in patients with "mild-to-moderate" liver dysfunction, especially in "elderly" patients, and "regular" monitoring in patients with renal impairment.
"Close monitoring" of serum potassium and renal function is recommended for patients who are prescribed eplerenone concomitantly with ACE inihibitors or angiotensin-II receptor antagonists. The SPC advises eplerenone should be used only with "caution" in pregnancy. It is not known whether the drug enters human milk
Patients who develop left ventricular systolic dysfunction (left ventricular ejection fraction 40% or less) complicated by heart failure (even if transient) after myocardial infarction are at higher risk of premature death than those with uncomplicated myocardial infarction. Mortality and morbidity in this population can be reduced by eplerenone (an aldosterone-receptor blocker( started 3–14 days after the infarct. The drug can cause hyperkalaemia and so necessitates monitoring of serum potassium concentrations. There is no evidence on the drug’s efficacy after 16 months of treatment. Conclusion
In theory, spironolactone (a much less expensive drug) might be expected to be as effective as eplerenone when used after myocardial infarction. However, there is no clinical trial evidence to support this and so we cannot recommend substituting spironolactone for eplerenone. There is no justification for using eplerenone outside the licensed indication (e.g. as a substitute for spironolactone in patients with chronic heart failure(.
Prominent U waves can easily be mistaken for T waves, leading to overestimation of the QT interval.This mistake can be avoided by identifying a lead where U waves are not prominent—for example, lead aVL.
In patients with a prior ischaemic stroke or transient ischaemic attack, adding the antiplatelet drug dipyridamole (modified release formulation, 200 mg twice daily) to aspirin reduces the relative risk of vascular events (stroke, myocardial infarction, or vascular death) by a fifth.In patients already receiving current secondary preventive treatment, the average annual risk of a vascular event is no more than 5% adding dipyridamole prevents one further vascular event for every 100 patients treated each year. Headache may occur in up to a third of people taking dipyridamole but usually settles in one to two weeks.
The second European stroke prevention study (ESPS-2) 3299 patients with a prior ischaemic stroke or transient ischaemic attack.
In developed countries up to a fifth of the population over the age of 60 has lower limb peripheral arterial disease, as defined by absent pulses or a reduced ankle brachial pressure index. About a quarter of these people have symptoms—most commonly intermittent claudication. When a patient with peripheral arterial disease needs diagnostic imaging, it seems sensible to start with the simplest and safest modality, which is undoubtedly duplex ultrasound. If ultrasound is not sufficient, then most clinicians would probably choose magnetic resonance angiography rather than computed tomographic angiography because it is more versatile, more accurate, is not as affected by arterial calcification, and does not involve exposing patients to ionising radiation. peripheral arterial disease
The low-flow and low-pressure venous system is susceptible to reduced blood flow (stasis) and systemic activation of the coagulation cascade, as Virchow described more than 150 years ago, which predisposes to a thrombus even in a nonstenotic vessel. Most venous thrombi consist predominantly of red cells enmeshed in fibrin and contain relatively few platelets; hence, they have been described pathologically as "red thrombi.“
In contrast, in the high-flow and high-pressure arterial system, thrombi form under the influence of local shear forces, platelet activation, and exposure to thrombogenic substances on damaged vascular surfaces. Arterial thrombi, referred to as "white thrombi," typically are composed predominantly of platelets with relatively little fibrin or red-cell accumulation. Thus, it is plausible to expect that an anticoagulant would be used to prevent venous thromboemboli, whereas an antiplatelet agent would be used to prevent arterial thrombosis.
Absolute risk of deep vein thrombosis in hospital
Prevalence of deep vein thrombosis (%)
Patient group10-20
General medical
15-40
General surgery
15-40
Major gynaecological surgery
20-50
Stroke
40-60
Hip or knee arthroplasty, hip fracture surgery
40-80
Major trauma
10-80
Critical care
People at high risk of cardiovascular disease should be treated more aggressively. This is the message from the American National Cholesterol Education Program published last year. By aggressively, it means that low density lipoprotein (LDL) cholesterol concentrations should be lowered to less than 1.81 mmol/l.
aggressive lipid lowering (IDEAL) trial, which compared usual dose simvastatin with 80 mg atorvastatin, no significant difference was seen on the major end points. However, the number of adverse effects were far higher than in any previous statin trial. Almost 90% of participants in both groups had side effects, and in almost half of them they were recorded as serious. All statins inhibit the synthesis of hydroxymethylglutaryl coenzyme A reductase, an enzyme involved in synthesis of the precursor of cholesterol and other important molecules such as coenzyme Q10, vital for mitochondrial energy production. Thus statins lower plasma Q10 concentrations and worsen cardiac function in patients with heart failure.
Are higher statin doses safe?
In conclusion, in patients with a recent stroke or TIA, treatment with 80 mg of atorvastatin per day decreased the risk of stroke, major coronary events, and revascularization procedures. These results support the initiation of atorvastatin treatment soon after a stroke or TIA.
Cholesterol is vital for the development and function of the brain. It is therefore unsurprising that reduced concentrations may produce mental and neurological complaints such as severe irritability, aggressive behaviour, suicidal impulses, cognitive impairment, memory loss, global amnesia, polyneuropathy, and erectile dysfunction. In many cases the symptoms were reversible and re-occurred after re-challenge
As a treatment for drug-refractory atrial fibrillation in patients with heart failure, pulmonary-vein isolation is more effective than atrioventricular-node ablation with biventricular pacing, new research indicates. At 6 months, patients in the pulmonary-vein isolation group had higher quality of life scores, longer 6-minute-walk distances, and higher ejection fractions than those in the AV node ablation group. studies are now underway to determine the best method for performing pulmonary vein isolation. N Engl J Med 2008
Adding aspirin to warfarin does not seem to prevent stroke and vascular events in patients with atrial fibrillation and stable vascular disease Bleeding risks are much higher in patients prescribed both warfarin and aspirin.
The perception that aspirin plus warfarin is needed in patients with atrial fibrillation and vascular disease is based on the fact that antiplatelet treatment works on the platelet-rich thrombus ("white clot") associated with vascular disease, whereas warfarin is effective for the fibrin-rich thrombus ("red clot") associated with atrial fibrillation, Also, in patients in atrial fibrillation with prosthetic heart valves, some may do better with warfarin plus aspirin.
In patients with atrial fibrillation who have such "unstable" vascular disease or valvular disease, the real, long term benefit to risk ratio of combination therapy is not known and should be left to the physician’s discretion. Aspirin plus clopidogrel (without warfarin) is not an alternative in patients with atrial fibrillation at high risk of stroke.
At least five animal experiments have found that the statins are carcinogenic. Nevertheless, the FDA approved them because cell experiments did not convincingly prove that statins were either mutagenic or genotoxic. But carcinogenicity may be due to the effects of statins on cholesterol because numerous cohort studies have found low cholesterol to be a risk factor for cancer. No increase of cancer was seen in a 10 year follow-up of participants in the Scandinavian simvastatin survival study, and the authors therefore concluded that 10 years of statin treatment does not induce cancer. Neither does 10 years' smoking tobacco.
It is estimated that half of patients with peripheral arterial disease have concomitant coronary artery disease. annual rate of myocardial infarction, stroke, or death from cardiovascular causes for patients with peripheral arterial disease was 5%. a risk of myocardial infarction or stroke that is three times as high as the risk in patients without peripheral arterial disease.
Peripheral arterial disease
It is estimated that half of patients with peripheral arterial disease have concomitant coronary artery disease. annual rate of myocardial infarction, stroke, or death from cardiovascular causes for patients with peripheral arterial disease was 5%. a risk of myocardial infarction or stroke that is three times as high as the risk in patients without peripheral arterial disease.
Two recently published clinical guidelines for treating peripheral arterial disease, the American College of Cardiology and American Heart Association guidelines and the Transatlantic Consensus Document on Peripheral Arterial Disease (often called TASC II), recommend long-term antiplatelet treatment to prevent cardiovascular events. reduction of approximately 25% in the risk of cardiovascular events.
After a mean follow-up of 35 months, patients randomly assigned to receive an oral anticoagulant plus an antiplatelet drug had an absolute but nonsignificant reduction in the combined end point of myocardial infarction, stroke, or death from cardiovascular causes as compared with patients assigned to antiplatelet treatment alone.
A significant increase in bleeding complications occurred in the combined-therapy group as compared with the single-therapy group. The reasons include advanced age, more widespread atherosclerosis, decreased integrity of the vessel wall, and increasing microvascular fragility. At this time, the data indicate that antiplatelet treatment alone affords a better outcome than does combined therapy with an anticoagulant in the long-term management of peripheral arterial disease.
B blockers are no longer recommended for the first line or second line treatment of hypertension, says an updated guideline for England and Wales. The guideline recommends that for hypertensive patients aged 55 or older or for black patients of any age the first choice for initial treatment should be either a calcium channel blocker or a thiazide-type diuretic.
For patients under the age of 55 an angiotensin converting enzyme (ACE) inhibitor (or an angiotensin receptor blocker if an ACE inhibitor is not tolerated) is recommended as first line treatment. Head to head trials showed that B blockers were usually less effective than the other drugs in reducing major cardiovascular events, particularly stroke. B blockers were also less effective than an ACE inhibitor or a calcium channel blocker in reducing the risk of type 2 diabetes; patients taking a B blocker and a thiazide-type diuretic were at particular risk.
High-density lipoprotein (HDL) cholesterol is an inverse predictor of coronary atherosclerotic disease. Preliminary data have suggested that HDL infusions can induce atherosclerosis regression. Sixty patients were randomly assigned to receive 4 weekly infusions of placebo (saline), 111 to receive 40 mg/kg of reconstituted HDL (CSL-111); and 12 to receive 80 mg/kg of CSL-111.
Short-term infusions of reconstituted HDL resulted in no significant reductions in percentage change in atheroma volume or nominal change in plaque volume compared with placebo but did result in statistically significant improvement in the plaque characterization index and coronary score on quantitative coronary angiography. Elevation of HDL remains a valid target in vascular disease and further studies of HDL infusions, including trials with clinical end points, appear warranted.
Long term follow-up assessed 10-15 years after the original trial. Dietary sodium reduction, including comprehensive education and counselling on reducing intake, for 18 months (TOHP I) or 36-48 months (TOHP II). Results 744 participants in TOHP I and 2382 in TOHP II were randomised to a sodium reduction intervention or control. Net sodium reductions in the intervention groups were 44 mmol/24 h and 33 mmol/24 h, respectively
Conclusion Sodium reduction, previously shown to lower blood pressure, may also reduce long term risk of cardiovascular events. The dietary approaches to stop hypertension (DASH-sodium) study offers strong evidence of short term effects on blood pressure in a dose-response fashion, and five large randomised trials that lasted at least one year have confirmed a modest effect of sodium reduction on blood pressure in those with high normal blood pressure (“prehypertension”).
an expanding body of evidence suggests that a high sodium intake has detrimental cardiovascular effects independent of blood pressure. High sodium intake increases extracellular sodium concentrations and may adversely affect vascular reactivity and growth and stimulate myocardial fibrosis. Additionally, several cross sectional studies and one small clinical study have documented a direct relation between sodium intake and left ventricular mass.
Patients taking a treatment for high blood pressure based on a calcium channel blocker had a 34% lower risk of developing diabetes than patients using a B - blocker. This result is from a substudy of the Anglo-Scandinavian cardiac outcomes trial )ASCOT) reported at the World Congress of Cardiology meeting in Barcelona.
Treating patients with amlodipine, with or without the angiotensin converting enzyme inhibitor perindopril, was associated with a 34% reduction in new onset diabetes compared with treatment with the blocker atenolol, with or without the diuretic bendroflumethiazide, the study showed.
ASCOT, the largest study of patients with hypertension yet conducted in Europe, included 19 257 hypertensive patients (160/100 mm Hg or higher untreated, or 140/90 mm Hg or higher after treatment with one or more drug) with no previous myocardial infarction or current clinical heart disease—and three or more other risk factors for coronary heart disease. Results showed that 1366 of the 14 120 patients who did not have diabetes at the start of the study developed the condition over the five year study period—567 (8%) in the amlodipine treated group and 799 (11%) in patients treated with atenolol (P=0.0001).
In 1989, two consecutive reports in Science described the cloning of vascular endothelial growth factor (VEGF). Napoleone Ferrara, the editor of Angiogenesis, was an author of one of the 1989 reports in Science; his laboratory not only cloned the VEGF gene but also developed the anti–VEGF monoclonal antibodies bevacizumab and ranibizumab, now (FDA) approved for the treatment of malignant and ocular diseases, respectively.
cumulative exposure to bacteremia from daily oral activities (e.g., chewing, brushing, flossing) is thousands of times greater than exposure from a few dental visits yearly.
Antibiotics not advised before dental work
In a marked departure from prior guidelines, new recommendations released by the American Heart Association emphasize that most patients undergoing dental procedures do not need antibiotics to prevent infective endocarditis, The new recommendations an artificial heart valve prior infective endocarditis certain congenital heart defects a cardiac transplant complicated by heart valve dysfunction1. Prophylaxis is now recommended only for patients with these four conditions: prosthetic cardiac valve previous infective endocarditis certain types of congenital heart disease cardiac transplantation with valvulopathy 2. For patients with the conditions listed above, prophylaxis should be given only before: dental procedures that involve manipulation of gingival tissue or the periapical region of teeth, or perforation of oral mucosa .incision or biopsy of respiratory tract mucosa,procedures on infected skin or musculoskeletal structures
3. Prophylaxis is no longer recommended for gastrointestinal or genitourinary procedures. However, if urine is colonized by enterococcus, eradication before invasive urinary procedures is reasonable. 4. A single 2-g dose of amoxicillin, given 30 to 60 minutes before the procedure, remains the regimen of choice .
The major changes in the updated recommendations include the following: (1) The Committee concluded that only an extremely small number of cases of infective endocarditis might be prevented by antibiotic prophylaxis for dental procedures even if such prophylactic therapy were 100% effective (2) Infective endocarditis prophylaxis for dental procedures should be recommended only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from infective endocarditis.
(3) For patients with these underlying cardiac conditions, prophylaxis is recommended for all dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa. (4) Prophylaxis is not recommended based solely on an increased lifetime risk of acquisition of infective endocarditis. (5) Administration of antibiotics solely to prevent endocarditis is not recommended for patients who undergo a genitourinary or gastrointestinal tract procedure.
Recommendation conditions as being at increased risk of developing infective endocarditis: acquired valvular heart disease with stenosis or regurgitation valve replacement structural congenital heart disease, including surgically corrected or palliated structural conditions, but excluding isolated atrial septal defect,fully repaired ventricular septal defect or fully repaired patent ductus and closure devices that are judged to be endothelialised previous infective endocarditis hypertrophic cardiomyopathy.
Recommendation Antibiotic prophylaxis against infective endocarditis is not recommended: for people undergoing dental procedures for people undergoing non-dental procedures at the following sites : upper and lower gastrointestinal tract genitourinary tract; this includes urological, gynaecological and obstetric procedures, and childbirth upper and lower respiratory tract; this includes ear, nose and throat procedures and bronchoscopy
Recommendation Chlorhexidine mouthwash should not be offered as prophylaxis against infective endocarditis to people at risk of infective endocarditis undergoing dental procedures.
Recommendation If a person at risk of infective endocarditis is receiving antimicrobial therapy because they are undergoing a gastrointestinal or genitourinary procedure at a site where there is a suspected infection, the person should receive an antibiotic that covers organisms that cause infective endocarditis.
Evidence statement There is insufficient evidence to determine whether or not antibiotic prophylaxis in those at risk of developing infective endocarditis reduces the incidence of IE when given before a defined interventional procedure (both dental and non-dental)
Younger women who take oestrogens to relieve menopausal symptoms can be reassured that the treatment won't increase their risk of heart disease, say researchers. . In a large randomised study women aged between 50 and 59 who took oestrogen only hormone replacement therapy after a hysterectomy developed significantly less coronary artery calcification than similar women given a placebo. Both groups took their pills for a mean of 7.4 years. These findings may be reassuring, but they don't necessarily indicate that oestrogens prevent heart disease, says the editorial. Doctors shouldn't be tempted to prescribe them for that purpose.
It now seems clear that magnetic resonance imaging (MRI) is better at detecting acute stroke than conventional computed tomography (CT), The difference was especially marked in the first few hours after onset of stroke, when critical decisions about management must be made. In this study, 90 patients presented within three hours of an acute ischaemic stroke. MRI detected 41 of the strokes, computed tomography only six.
Hypertrophic cardiomyopathy is the most common familial genetic disease of the heart (1/500 to 1/1000), as well as the most common cause of sudden cardiac death in young people and athletes
It is characterised by marked and asymmetric left ventricular hypertrophy, a non-dilated left ventricular cavity, diastolic impairment, usually preserved systolic function and, in about 20% of patients, left ventricular outflow obstruction at rest caused by mitral-septal contact during systole. Many patients remain asymptomatic throughout life, others develop heart failure or atrial fibrillation, and some die suddenly, The cardioverter defibrillator is the only effective treatment for the prevention of sudden death .
Medical treatment with B - blockers or verapamil improves symptoms of heart failure but has not been shown to modify the clinical course. B-blockers By reducing the heart rate, these drugs prolong diastole and improve ventricular filling. B -blockers may also decrease the outflow gradient during effort. Verapamil may be used in patients without severe outflow obstruction and is the drug of first choice in patients whose main symptom is chest pain. In patients with heart failure despite treatment with blockers or verapamil, the addition of diuretics in low doses is usually effective in alleviating symptoms
Patients with a marked outflow obstruction (outflow gradient 50 mm Hg under basal conditions) and severe symptoms (New York Heart Association functional class III or IV) unresponsive to medical therapy represent about 5% of patients with hypertrophic cardiomyopathy and are candidates for either ventricular septal surgical myectomy or percutaneous alcohol septal ablation to relieve the outflow obstruction.
The operation enlarges the outflow tract through a resection of a small amount of muscle (5-8 g) from the hypertrophied septum. In centres with extensive experience with the procedure, operative mortality is 1-3%The operation abolishes the outflow pressure gradient in about 90% of patients and improves symptoms (to functional class I or II) in about 70%.
Omega 3 fats may protect against cardiovascular disease by lowering blood pressure and heart rate; reducing serum triglycerides, thrombotic tendency, inflammation, and arrhythmias; and improving endothelial function, insulin sensitivity, paraoxonase concentrations, and plaque stability.
Results Of 15 159 titles and abstracts assessed, 48 RCTs (36 913participants) and 41 cohort studies were analysedLong chain and shorter chain omega 3 fats do not have a clear effect on total mortality, combined cardiovascular events, or cancer Some effects of fish on health may be due to components other than omega 3—for example, selenium or vitamin D.
Toxic compounds, such as fat soluble methylmercury, dioxins, and polychlorinated biphenyls, are also found in oily fish and fish oils, but any harm from these compounds would be seen only after long term supplementation Animal intervention studies and studies of adults after severe inadvertent exposure indicate that dioxins and polychlorinated biphenyls increase the risk of cancer.Methylmercury may increase the risk of myocardial infarction and cause neurological damage.
UK guidelines encourage the general public to eat more oily fish, and higher amounts are advised after myocardial infarction . This advice should continue at present but the evidence should be reviewed regularly. It is probably not appropriate to recommend a high intake of omega 3 fats for people who have angina but have not had a myocardial infarction To understand the effects of omega 3 fats on health, we need more high quality RCTs of long duration that also report the associated harms.
total of 1188 patients with coronary disease underwent intravascular ultrasonography. After treatment with atorvastatin to reduce levels of low-density lipoprotein (LDL) cholesterol to less than 100 mg per deciliter (2.59 mmol per liter), patients were randomly assigned to receive either atorvastatin monotherapy or atorvastatin plus 60 mg of torcetrapib daily. After 24 months, disease progression was measured by repeated intravascular ultrasonography in 910 patients (77%(.
(cholesteryl ester transfer protein)
After 24 months, as compared with atorvastatin monotherapy, the effect of torcetrapib–atorvastatin therapy was an approximate 61% relative increase in HDL cholesterol and a 20% relative decrease in LDL cholesterol, reaching a ratio of LDL cholesterol to HDL cholesterol of less than 1.0. Torcetrapib was also associated with an increase in systolic blood pressure of 4.6 mm Hg. The percent atheroma volume (the primary efficacy measure) increased by 0.19% in the atorvastatin-only group and by 0.12% in the torcetrapib–atorvastatin group (P=0.72). A secondary measure, the change in normalized atheroma volume, showed a small favorable effect for torcetrapib (P=0.02), but there was no significant difference in the change in atheroma volume for the most diseased vessel segment.
Conclusions The CETP inhibitor torcetrapib was associated with a substantial increase in HDL cholesterol and decrease in LDL cholesterol. It was also associated with an increase in blood pressure, and there was no significant decrease in the progression of coronary atherosclerosis. The lack of efficacy may be related to the mechanism of action of this drug class or to molecule-specific adverse effect.
We derived and validated a new cardiovascular disease risk equation (QRISK) in the United Kingdom in readiness for a major change in national policy on the identification of patients at high risk of cardiovascular disease. It is the largest such study to have ever been undertaken . QRISK includes standard as well as additional risk factors for cardiovascular disease, such as deprivation, family history of premature coronary heart disease, body mass index, and the effect of existing antihypertensive treatment.
QRISK
Using QRISK we estimate that 34% of women and 73% of men aged 64-75 would be at high risk compared with 24% and 86% according to the Framingham equation. UK estimates on the basis of QRISK give 3.2 million patients at high risk in 2005, compared with 4.71 million for the Framingham equation and 5.1 million for ASSIGN. Overall, QRISK would reclassify about 1 in 10 patients from high to low risk or vice versa compared with the Framingham algorithm.
We think that QRISK is likely to provide more appropriate estimates of cardiovascular disease risk in contemporary UK populations and better discriminate those at high risk on the basis of their age, sex, and social deprivation as well as existing antihypertensive treatment. It is likely therefore to be a more equitable tool to inform patient management decisions.
The rate of attempts to stop is high—78 attempts per 100 smokers per year in the UK—with many smokers making several attempts in a year. Nearly half of all smokers expect not to be smoking in a year's time, but only 2-3% actually stop permanently each year. The most common reasons smokers give for smoking are stress relief and enjoyment,4 but the main reason is nicotine dependence. Nicotine acts in the midbrain, creating impulses to smoke in the face of stimuli associated with smoking. Consequent changes in brain chemistry also produce "nicotine hunger" when a smoker goes without nicotine. A third mechanism underlying nicotine dependence is nicotine withdrawal: unpleasant mood and physical symptoms that occur on abstinence and are relieved by smoking.
Stopping smoking before the age of 40 is crucial to improve health—beyond 40, people lose three months of life expectancy for every further year smoking. The most important factor leading to failure of attempts to stop is nicotine dependence. Nicotine dependence is most effectively treated with a combination of drugs and specialist behavioural support, such as provided by the NHS Stop Smoking Service. Varenicline, bupropion, nortriptyline, and nicotine replacement are all effective. Relapse during or after treatment is common, and treatment is usually needed several times.
US and UK guidelines propose the "five A's": Ask about smoking. Advise patients to stop, Assess motivation to stop and need for pharmacotherapy, Assist with prescription or referral to a behavioural support programme, and Arrange follow-up. A meta-analysis of more than 100 randomised controlled trials shows that all forms of nicotine replacement therapy are roughly equally effective in aiding long term cessation.
Antidepressants. A systematic review showed that people who stop smoking experience depressed mood as a withdrawal symptom, so it is logical to use antidepressants as cessation treatment. One antidepressant, bupropion A new drug :Varenicline is a newly licensed partial agonist acting on the alpha 4 beta2 nicotinic receptor. Bupropion, nicotine replacement therapy, and varenicline are reasonable first line choices, with nortriptyline used second line . There is insufficient information to know which elements of behavioural support are effective or whether one approach, such as motivational interviewing or cognitive behavioural therapy, is more effective than another. There is some evidence to suggest that group support may be more effective in general than one-to-one support,34 and that it should involve multiple sessions.
Bupropion Start bupropion while smoking and quit smoking in the second week. Use 150 mg per day for six days, then 150 mg twice a day for eight weeks. Take the evening dose early to avoid wakefulness. Causes 1 in 1000 to have a seizure, which needs discussion with patient NortriptylineStart nortriptyline while smoking, increasing the dose from 25 mg to 75 mg. Quit while taking the maximum dose and continue for 8-12 weeks, tapering down at the end. Reassure patients that side effects abate in time and fewer than 1 in 10 patients stop because of side effects. VareniclineStart varenicline while smoking. Comes in a starter pack escalating the dose from 0.5 mg daily to 1 mg twice a day by the second week. Quit in the second week. Continue for 12 weeks. Most people experience mild to moderate nausea, which can be reduced by taking varenicline after food and with water. Take the evening dose early to avoid wakefulness. Side effects abate with time and fewer than 1 in 10 patients stop the drug.
Nicotine replacement patches Put the patch on smooth, hairless skin. Avoid using the same site for all patches. Put the 24 hour patches on the night of the last cigarette. If it slides off, tape it on with micropore. Skin reactions are common: check site rotation, use an emollient or hydrocortisone cream, consider changing the make of patch or switching to another form of nicotine replacement.
Deprivation of cardiac energy has a major role in heart failure. The heart consumes more energy than any other organ. It cycles about 6 kg of ATP every day — 20 to 30 times its own weight. Each day, it beats about 100,000 times and pumps approximately 10 tons of blood through the body. To acquire the energy that is necessary to carry out its function, the heart converts chemical energy stored in fatty acids and glucose into the mechanical energy of the actin–myosin interaction of myofibrils. Failure to produce an adequate amount of energy causes mechanical failure of the heart.
The metabolic machinery has three main components. The first is substrate utilization — the use of fuel that comes from food. This process entails the cellular uptake of mainly free fatty acids and glucose, the breakdown of these components by beta-oxidation and glycolysis, and the entry of the resulting intermediary metabolites into the Krebs cycle.
2. The second component is oxidative phosphorylation — the production of energy by the mitochondrial respiratory chain. The phosphorylation of ADP by this mechanism produces the high-energy phosphate compound ATP, which is the direct source of energy for all energy-consuming reactions in the heart. 3. The third component is ATP transfer and utilization — the transport of energy to and its consumption by the heart's motor, the myofibrils. This process entails an energy-transfer mechanism termed the creatine kinase energy shuttle
mitochondrial creatine kinase catalyzes the transfer of the high-energy phosphate bond in ATP to creatine to form phosphocreatine and ADP. Phosphocreatine, a smaller molecule than ATP, rapidly diffuses from the mitochondria to the myofibrils, where myofibrillar creatine kinase catalyzes the reformation of ATP from phosphocreatine. The free creatine, formed by the removal of phosphate from phosphocreatine, diffuses back to the mitochondria. Creatine is produced by the liver and kidneys
creatine kinase system is to act as an energy buffer. When the energy demand outstrips the energy supply, the phosphocreatine level falls, keeping ATP at a normal level, but the free ADP level rises. The increased level of free ADP inhibits the function of many intracellular enzymes, causing failure of the heart's contraction mechanism. Thus, a metabolic derangement in the cardiac myocyte can occur when phosphocreatine levels fall and free ADP levels rise, even if ATP levels remain unchanged.
ACE inhibitors, diuretics, and beta-blockers may have indirect metabolic effects on the heart, but they do not directly affect energy metabolism. Could energy metabolism be a specific target for therapy in patients with heart failure? Modulation of Substrate Utilization Modulation of Oxidative Phosphorylation Manipulation of High-Energy Phosphate Metabolites
In a study of eight patients with heart failure, intracoronary infusion of pyruvate improved cardiac function in the short term, Regardless of the theoretical arguments, a number of recent proof-of-principle clinical studies have suggested that partial inhibition of fatty acid oxidation is promising. For example, treatment with trimetazidine, an inhibitor of fatty acid oxidation, improved left ventricular function over a period of 6 months in elderly patients.
Small, single-center, and thus far unconfirmed studies have shown that in patients with heart failure of ischemic or nonischemic origin, 2 months of treatment with the fatty acid oxidation inhibitor perhexiline or 3 months of treatment with the carnitine palmitoyl transferase 1 inhibitor etoxomir improved the left ventricular ejection fraction. The effects of PPAR activators on cardiac substrate utilization are complex .
Currently, however, there are no effective stimulators of oxidative phosphorylation. Even so, increasing PCG-1 activity as a means of up-regulating oxidative phosphorylation enzymes may be a promising approach. An alternative is to reduce free fatty acid levels, which should repress mitochondrial uncoupling proteins, thereby increasing ATP synthesis.
A third strategy for metabolic intervention is the direct manipulation of high-energy phosphate stores, their availability, or the efficiency of their utilization. Although massive increases in the creatine transporter function are detrimental (because a substantially supranormal creatine level increases the free ADP level), future studies will show whether reversing the decrease in creatine and phosphocreatine levels by moderate stimulation of creatine transporter activity is beneficial in heart failure. Finally, it may be feasible to improve the myofibrillar efficiency of ATP utilization with new calcium-sensitizing or myosin activator compounds.
The analysis of ATP and phosphocreatine in tissue samples is problematic, however, because of the instability of these molecules. For this reason, the principal method for measuring ATP and phosphocreatine is phosphorus-31 magnetic resonance (31P-MR) spectroscopy. The most powerful method for assessing energy metabolism in heart failure entails the in vivo assessment of turnover rates of glucose and fatty acids and rates of oxidative phosphorylationand ATP transfer .
Substrate utilization can become limiting for cardiac function in heart failure as a result of reduced substrate uptake, oxidation, or both. Impaired oxidative phosphorylation can reduce cardiac function by providing an insufficient supply of ATP to cardiac myocytes. Impaired ATP transfer and utilization may limit contractile function by means of a decrease in the average ATP concentration .
There are profound changes in the creatine kinase system in heart failure. Mitochondrial creatine kinase activity may be reduced to as little as 20% of normal activity, and myofibrillar creatine kinase activity can decrease by up to 50% as compared with normal values. The losses of high-energy phosphates and creatine kinase activity cause a severe decline in ATP transfer— that is, a decrease in energy flux within the cell — and thus a reduction in energy delivery to the myofibrils by up to 71%. This metabolic abnormality may contribute to contractile dysfunction and particularly to the loss of inotropic reserve that is characteristic of the myocardium in heart failure.
Metabolic therapy is a promising new avenue for the treatment of heart failure, and suitable targets for therapy are substrate utilization, oxidative phosphorylation, and the availability of high-energy phosphates.New metabolic modulator compounds need to be developed by academia and industry. large-scale clinical trials will have to prove or disprove the clinical efficacy of metabolic modulators. These therapies may improve the symptoms and prognosis of patients with the life-threatening illness of chronic heart failure.
30 to 40% of patients die from heart failure within 1 year after receiving the diagnosis, with an annual mortality rate of 10%. Chronic heart failure is multifactorial but the available evidence suggests that the failing heart is an engine out of fuel — that is, altered energetics play an important role in the mechanisms of heart failure. For this reason, the modulation of cardiac metabolism has promise as a new approach to the treatment of heart failure. today, energy metabolism in the heart — myocardial energetics — is a topic of considerable interest.
A major reason for the attention to this topic is that any energy-sparing treatment for heart failure such as beta-receptor blockers, ACE inhibitors, or angiotensin II blockers improves the prognosis. The failing heart has been compared to a weak and tired horse, and if this horse is nourished properly, it can recover and work in the long term, albeit at a reduced level.
A left ventricular assist device (LVAD) is a battery-operated, mechanical pump-type device that's surgically implanted. It helps maintain the pumping ability of a heart that can't effectively work on its own. This device is sometimes called a "bridge to transplant." People awaiting a heart transplant.
A common type of LVAD has a tube that pulls blood from the left ventricle into a pump. The pump then sends blood into the aorta .This effectively helps the weakened ventricle. The pump is placed in the upper part of the abdomen. Another tube attached to the pump is brought out of the abdominal wall to the outside of the body and attached to the pump's battery and control system. LVADs are now portable and are often used for weeks to months. Patients with LVADs can be discharged from the hospital and have an acceptable quality of life while waiting for a donor heart to become available.
Numerous drugs (e.g., angiotensin converting–enzyme [ACE] inhibitors or angiotensin-receptor blockers, beta-blockers, and aldosterone blockers) and electrophysiological devices may temporarily halt, slow, or even reverse the pathophysiological processes in patients with stage C heart failure. Reversion of the heart toward more normal shape and function is called reverse remodeling. ). Life expectancy for patients with stage D heart failure is short, with a 1-to-2-year survival rate of less than 50 percent.
End-of-life strategies, transplantation, or permanent support with a left ventricular assist device (LVAD) is required. In selected patients, the LVAD may serve as a platform for the administration of therapies that enable reverse remodeling that is sufficient to allow removal of the device. These may be pharmacologic, gene-based, or cell-based therapies. With such an approach, stage D heart failure may revert to stage C.
A nuclear-receptor coactivator, PPAR coactivator-1 (also known as PCG-1 ), is a master regulator of metabolic function in mitochondria. It activates multiple genes that are responsible for fatty acid uptake and oxidation and for oxidative phosphorylation. These genes include PPAR and PPAR and nuclear respiratory factors 1 and 2. Experimental studies suggest that the inhibition of PCG-1 , probably as a direct consequence of high plasma catecholamine levels, leads to down-regulation of mitochondrial gene expression.
In this way, it contributes to the impairment of oxidative phosphorylation in the failing heart. The development of heart failure is accelerated by PCG-1 deficiency, suggesting that this coactivator may have a cardioprotective function. the down-regulation of PPAR is thought to be the main mechanism underlying the switch in substrate utilization from fatty acids to glucose. This switch is typical of the hypertrophied heart.
Women with heart disease or with an increased risk for it receive little benefit from antioxidants, according to a long-term study published in the Archives of Internal Medicine. Researchers randomized almost 8200 women aged 40 and older with a history of cardiovascular disease or at least three risk factors to receive supplements of vitamin C, E, beta carotene, or placebo. The study's design allowed testing of the supplements' individual effects as well as any interactions with each other.
After a mean follow-up of roughly 9 years, the primary endpoint — a composite of MI, stroke, revascularization, or death from cardiovascular disease — was no less frequent among recipients of the individual or combined antioxidants. A marginal benefit against stroke was seen in patients taking vitamins C and E in combination..
The study included 108 patients aged 17 to 69 who received increasing dosages of verapamil every 2 weeks until cluster headache was suppressed, side effects interfered, or a maximum dosage of 960 mg/day was reached. Electrocardiograms were performed with each dosage increase.
Arrhythmias, including first-degree heart block, were detected in about 20% of patients, one of whom required a permanent pacemaker. In addition, 39 patients (36%) developed bradycardia, although this led to drug discontinuation in only 4. EKG abnormalities occurred at dosages as low as 240 mg/day.The authors say their study "highlights the need for careful EKG monitoring of patients with CH while on verapamil" — a treatment "widely regarded as the drug of choice for the preventive treatment of CH."
Several studies have shown that left ventricular hypertrophy is an important risk factor in patients with hypertension, leading to a fivefold to 10-fold increase in cardiovascular risk, which is similar to the increase seen in patients with a history of myocardial infarction.
The presence of left ventricular hypertrophy, in addition to hypertension, thus has important implications for assessing risk and managing patients, including decisions on interventions other than antihypertensive treatment, such as lipid lowering treatment and lifestyle modifications. Accurate and early diagnosis of left ventricular hypertrophy is therefore an important component of the care of patients with hypertension
Sokolow-Lyon index—sum of SV1+RV5 or V6>3.5 mV Cornell voltage index—men: RaVL+SV3>2.8 mV;women: RaVL+SV3>2.0 mV Cornell product—men: (SV3+RaVL)ЧQRS duration≥2440 ms; women:(SV3+(RaVL+8 mV))ЧQRS duration>2440 ms Gubner—RI+SIII≥25 mV Romhilt-Estes scores—excessive amplitude: 3 points (largest R or S wave in limb leads ≥20 mV or S wave in V1 or V2 ≥30 mV or R wave in V5 or V6 ≥30mV).
ST-T segment pattern of LV strain: 3 points(ST-T segment vector shifted in direction opposite to mean QRS vector). Left atrial involvement: 3 points (terminal negativity of P wave in V1≥1 mm withduration ≥0.04 s). Left axis deviation: 2 points (leftaxis ≥−30° in frontal plain). Prolonged QRS duration: 1 point (≥0.09 s). Intrinsicoid deflection: 1 point (intrinsicoid deflection in V5 orV6≥0.05 s). Two thresholds in use: positive if ≥4 points or ≥5 points
The British Heart Foundation advises patients with known ischaemic heart disease that chest pain that lasts more than 15 minutes is probably a heart attack. Within this time patients are advised to use their glyceryl trinitrate (GTN) spray three times at five minute intervals before calling an ambulance.The recommendations of the American College of Cardiology and American Heart Association one GTN spray and 5 minutes" before calling an ambulance .
The evidence for early presentation and treatment of STEMI has long been established. Necrosis of viable myocardium predominantly occurs between 30 to 90 minutes after coronary artery occlusion. This has formed the basis of "the golden hour" during which prompt reperfusion strategies (thrombolysis or primary angioplasty) prevent extensive myocardial necrosis that leads to left ventricular dysfunction and worse prognosis. Even before angioplasty became widely used, thrombolysis within the first hour cut deaths by half .
Most acute coronary syndromes occur in people already known to have ischaemic heart disease or to be at high risk. In this group the risk of subsequent myocardial infarction or death is 5-7 times higher than in the general population, and at least 70% of deaths from coronary heart disease occur in people who have had previous manifestations of cardiovascular disease.
The prevalence of atrial fibrillation rises with age from 1.5% in people in their 60s to more than 10% in those over 90. People with atrial fibrillation have double the mortality and a four to fivefold higher risk of stroke than those without fibrillation. About a quarter of all strokes in elderly people are caused by atrial fibrillation. Strokes caused by atrial fibrillation are often severe and lead to high mortality and a low quality of life.
Even if normal rhythm cannot be restored, antiplatelet agents reduce the risk of stroke by around 22% vitamin K antagonists such as warfarin, reduce the risk by 64%
those who are symptomatic younger patients those presenting for the first time with lone AF those with AF secondary to treated/corrected precipitant those with congestive heart failure.
1. contraindications to anticoagulation. 2. structural heart disease (e.g. large left atrium >5.5 cm, mitral stenosis) that precludes long-term maintenance of sinus rhythm. 3.a long duration of AF (usually >12 months). 4.a history of multiple failed attempts at cardioversion and/or relapses. 5.an ongoing but reversible cause of atrial fibrillation (e.g. thyrotoxicosis).
Before cardioversion, patients should be maintained on therapeutic anticoagulation with warfarin (INR 2.5, range 2.0 to 3.0) for a minimum of 3 weeks. Following successful cardioversion, patients should remain on therapeutic anticoagulation with warfarin (INR 2.5, range 2.0 to 3.0) for a minimum of 4 weeks.
In patients with persistent AF where cardioversion cannot be postponed for 3 weeks: heparin should be given and the cardioversion performed, and warfarin should then be given for a minimum of 4 weeks post cardioversion.
In patients with AF of confirmed duration of less than 48 hours undergoing cardioversion, anticoagulation following successful restoration of sinus rhythm is not required.
In patients with permanent AF a risk–benefit assessment should be performed and discussed with the patient to inform the decision whether or not to give antithrombotic therapy.In patients with permanent AF where antithrombotic therapy is given to prevent strokes and/or thromboembolism • adjusted-dose warfarin should be given as the most effective treatmentadjusted-dose warfarin should reach a target INR of 2.5 (range 2.0 to 3.0) where warfarin is not appropriate, aspirin should be given at 75 to 300 mg/day • where warfarin is appropriate, aspirin should not be coadministered with warfarin purely as thromboprophylaxis, as it provides no additional benefit.
In the general AF population, the evidence suggests that combined therapeutic anticoagulation with antiplatelet therapy does not reduce the incidence of stroke or thromboembolism compared to therapeutic anticoagulation alone, and it may increase the incidence of bleeding. However, it is unclear whether there are certain subgroups of patients with AF for whom the therapeutic effects of combination therapy may be greater than either monotherapy. In particular, it is unclear whether combination therapy is justified in those AF patients who have stent implantation or a history of myocardial infarction.
The frequency of paroxysms in patients with paroxysmal AF varies widely between patients. It remains unclear, however, whether the risk of stroke or thromboembolism varies between those with only infrequent paroxysms and those with more frequent paroxysms. It is also unclear whether, if the risk of stroke or thromboembolism is reduced in those with infrequent paroxysms, the use of anticoagulation is justified in such a low-risk group.
In all patients with AF who have had an acute stroke, any uncontrolled hypertension should be appropriately managed before antithrombotic therapy is started. In patients with AF and an acute stroke: imaging (CT scan or MRI) should be performed to exclude cerebral haemorrhage. in the absence of haemorrhage, anticoagulation therapy should begin after 2 weeks in the presence of haemorrhage, anticoagulation therapy should not be given. in the presence of a large cerebral infarction, the initiation of anticoagulation therapy should be delayed.
imaging (CT scan or MRI) should be performed to exclude recent cerebral infarction or haemorrhage in the absence of cerebral infarction or haemorrhage, anticoagulation therapy should begin as soon as possible.
. Particular attention should be paid to patients who: are over 75 years of ageare taking antiplatelet drugs (such as aspirin or clopidogrel) or non-steroidal anti-inflammatory drugsare on multiple other drug treatments (polypharmacy)have uncontrolled hypertension • have a history of bleeding (for example, peptic ulcer or cerebral haemorrhage) • have a history of poorly controlled anticoagulation therapy.
Referral for further specialist intervention pulmonary vein isolationpacemaker therapy arrhythmia surgeryatrioventricular junction catheter ablation atrial defibrillators should be considered in the following patients: those in whom pharmacological therapy has failedthose with lone AFthose with ECG evidence of an underlying electrophysiological disorder (such as Wolff–Parkinson–White syndrome).
Atrial fibrillation is an enormous health concern because it increases the risk of death, congestive heart failure, and thromboembolism and decreases the quality of life. It places an increasing burden on the health care system because of the associated costs of hospitalization and outpatient care. The pharmacologic approach to the maintenance of sinus rhythm in patients with atrial fibrillation is compromised by its limited efficacy, side effects, and concern about safety. The importance of the pulmonary veins and surrounding left atrium in the initiation of atrial fibrillation is now widely accepted by electrophysiologists.
Electrical isolation of the pulmonary veins by radiofrequency catheter ablation has a success rate approaching 75 to 85 percent in patients without clinically significant structural heart disease According to the latest guidelines of the American Heart Association, the American College of Cardiology, and the European Society of Cardiology, catheter ablation is considered standard therapy for patients who have symptomatic paroxysmal atrial fibrillation after having had no response to a single antiarrhythmic drug. atrial tissue damage following the procedure has not been evaluated. The ablation procedure, based on electrical isolation of the pulmonary veins in all patients, with additional left atrial linear ablation when necessary.
Though the results of catheter ablation for atrial fibrillation have been steadily improving, with the rate of success often reported as more than 80 percent for paroxysmal atrial fibrillation, ablation of permanent atrial fibrillation has been more difficult and has required more extensive atrial ablation and often multiple procedures.
Complications have been infrequent (usually occurring in less than 1 percent of patients) but have included pericardial tamponade and stroke. The results can be expected to improve with a better understanding of the substrate maintaining atrial fibrillation and with the development of more effective techniques.
Curative ablation for atrial fibrillation offers the unique opportunity to maintain sinus rhythm without antiarrhythmic drugs, which can have deleterious effects. Our study shows that restoration and long-term maintenance of sinus rhythm are associated with significant improvement in cardiac function, symptoms, exercise capacity, and quality of life in patients with congestive heart failure, even in the presence of concurrent heart disease and adequate rate control
In contrast to its established use for paroxysmal atrial fibrillation, the role of catheter ablation for chronic atrial fibrillation is less well studied. Evidence to date suggests that the mechanisms of chronic atrial fibrillation are more complex than those causing paroxysmal atrial fibrillation. The use of more extensive ablation procedures that modify the electrical substrate as well as the initiators of atrial fibrillation is often necessary to prevent chronic atrial fibrillation.
Few studies have systematically examined the results of catheter ablation in patients with chronic atrial fibrillation. younger patients who are refractory to medical treatment and who have limited or no structural heart disease may be most likely to benefit from this procedure.
In the recently reported substudy of the AFFIRM trial, restoration and maintenance of sinus rhythm were associated with a 47 percent reduction in the risk of death, as compared with that of patients who were in atrial fibrillation, whereas the use of antiarrhythmic drugs and the presence of congestive heart failure significantly increased the risk of death, by 49 percent and 57 percent, respectively, thereby reversing the benefit of the restoration of sinus rhythm. The maintenance of sinus rhythm without antiarrhythmic drugs may thus be of critical importance and can now be achieved through curative ablation with the use of catheter or surgical techniques.
Atrial fibrillation is the most common cardiac arrhythmia seen in clinical practice.The actual mechanism of atrial fibrillation is probably a focal source of automatic firing, a series of small reentrant circuits, or a combination of the two. The hemodynamic consequences of atrial fibrillation result primarily from the loss of atrioventricular synchrony but also from the rapid rate and irregularity of the ventricular response.
Patients with clinical syndromes that impair diastolic compliance (e.g., left ventricular hypertrophy) are most likely to have functional deterioration and symptoms, with loss of the atrial contribution to ventricular filling; such patients are also therefore most likely to benefit from restoration of sinus rhythm.
Strategies to maintain sinus rhythm have not been shown to reduce total mortality or the risk of stroke but have been shown to improve functional capacity and quality of life. The failure to reduce the mortality associated with rhythm-control strategies is in part due to the toxicity of the therapies used to maintain sinus rhythm.
The precise mechanism through which antiarrhythmic drugs such as amiodarone suppress atrial fibrillation remains unknown. Amiodarone (with its active metabolite, desethylamiodarone) blocks sodium, potassium, and calcium channels. It is also a relatively potent noncompetitive alpha-blocker and beta-blocker but has no clinically significant negative inotropic effect. Most important, potassium-channel blockade slows repolarization, causing an increase in the duration of the action potential and in the refractoriness of cardiac tissue; this has the effect of prolonging the QT interval.
Amiodarone has consistently been demonstrated to be superior to other antiarrhythmic medications for the maintenance of sinus rhythm. Recurrence of atrial fibrillation after 1 year was documented in 35% of patients taking amiodarone, 60% of those taking sotalol, and 82% of those taking placebo. Amiodarone is approved by the Food and Drug Administration for the treatment of lethal ventricular arrhythmias but not for the management of atrial fibrillation. Nonetheless, it is widely prescribed for this indication.
The safe and effective use of amiodarone requires a firm understanding of its unusual pharmacokinetics as well as the potential for drug interactions and adverse events. Amiodarone is a highly lipophilic compound with a large volume of distribution (66 liters per kilogram of body weight). This property results in a delayed onset of action (an interval of 2 to 3 days) and a long elimination half-life (up to 6 months).
Amiodarone is metabolized to desethylamiodarone in the liver, and its use should be avoided in patients with advanced hepatic disease. There is no clinically significant renal metabolism of amiodarone, and the dose is not affected by renal dysfunction or dialysis. Amiodarone crosses the placenta in pregnant women and is excreted in varying amounts in breast milk. Its use should therefore be avoided in women who are pregnant or breast-feeding.
Amiodarone is an excellent choice for use in patients with structural heart disease or congestive heart failure. It is generally reserved as an alternative to other agents for patients without underlying heart disease, given its multitude of side effects. Many physicians hesitate to use amiodarone in young patients because of the concern about side effects related to long-term use.
Amiodarone is frequently used for the prevention and treatment of atrial fibrillation associated with cardiac surgery, including the maze procedure for cure of atrial fibrillation. Atrial fibrillation associated with cardiac surgery occurs most frequently in the first few days after surgery but can also occur weeks after surgery. For patients undergoing cardiac surgery, amiodarone is given at a dose of 600 mg a day for 1 to 2 weeks before surgery and is continued for 4 to 6 weeks after surgery.
Amiodarone therapy is initiated with a loading dose of approximately 10 g in the first 1 to 2 weeks. This loading dose can be given in divided doses — for example, 400 mg given orally twice a day for 2 weeks followed by 400 mg given orally each day for the next 2 weeks. Electrocardiographic monitoring (with 12-lead electrocardiography or an event recorder) should be performed at least once during the loading period to evaluate the patient for excessive prolongation of the QT interval (>550 msec) or bradycardia. Prolongation of the QT interval is common and generally responds to dose reduction. Approximately 30% of patients have a reversion to sinus rhythm during this loading phase, and the remainder can undergo electrical cardioversion, which has a high rate of success.
Once the loading phase is completed, the maintenance dose of amiodarone for atrial fibrillation is 200 mg a day. Monitoring of levels of amiodarone or desethylamiodarone is not recommended, given the lack of correlation between drug levels and efficacy or adverse events. However, monitoring with the use of various laboratory tests for evidence of adverse effects is recommended. A miodarone interferes with the hepatic metabolism of many medications, the most common of which are digoxin and warfarin. Generally, digoxin should be discontinued if possible, or the dose at least reduced by 50%. The INR must be monitored closely during amiodarone loading and maintenance therapy. It is usually necessary to reduce the warfarin dose by 25 to 50% when the drug is coadministered with amiodarone.
The cost of amiodarone is typically about $1.25 per tablet in the United States. In addition, the initial screening tests performed before treatment begins (chest radiography and tests of pulmonary, thyroid, and liver function) cost approximately $250, with a similar expense annually to screen for adverse effects.
Amiodarone is associated with both cardiovascular and noncardiovascular adverse events. Side effects resulting in discontinuation of therapy occur in 13 to 18% of patients after 1 year. , The most frequent cardiovascular side effect is bradycardia, which is often dose-related, occurs more frequently in elderly patients than in younger patients, and can often be mitigated by dose reduction. Prolongation of the QT interval is seen in most patients but is associated with a very low incidence of torsades de pointes (<0.5%) as compared with other drugs that prolong the QT interval (e.g., sotalol and dofetilide).
Clinical evidence of hypothyroidism occurs in up to 20%. Hyperthyroidism occurs in 3% of patients in areas where dietary iodine is sufficient but in 20% of patients in iodine-deficient areas. Thyrotropin levels should be checked in all patients before amiodarone therapy is initiated and at least every 6 months thereafter. Pulmonary toxicity is one of the most serious complications of amiodarone use. It occurs in less than 3% of patients
The management of acute pulmonary toxicity involves discontinuation of therapy, supportive management, and, in extreme cases, corticosteroid administration. Screening pulmonary-function tests and chest radiography should be performed at baseline, and chest radiography should be performed yearly thereafter. Pulmonary-function tests should be repeated if symptoms develop.
Hepatic toxicity is a rare complication of amiodarone therapy when the drug is used in low doses,This condition can generally be reversed by discontinuing the drug but can result in cirrhosis if unheeded. Liver-function tests should be measured at baseline and every 6 months thereafter. Corneal microdeposits are seen in virtually all patients receiving long-term amiodarone therapy and are rarely of clinical significance. Optic neuropathy has been reported in less than 1% of patients. Photosensitivity
Neurologic side effects, which occur in up to 30% of patients, include ataxia, tremor, peripheral polyneuropathy, insomnia, and impaired memory. These effects are often dose-related and occur more often in elderly patients than in younger patients. The side effects of low-dose amiodarone therapy (200 mg daily) in patients taking the drug for more than 5 years. are unknown Some patients, particularly those who are elderly and those with relatively little body fat, can be treated with a very low dose (100 mg per day). There are no available data from clinical trials that support this reduced-dose strategy, but it is common practice .
severe sinus-node dysfunction and advanced conduction disease (except in patients with a functioning artificial pacemaker). The drug should also be used cautiously in patients with severe lung disease (which may interfere with the detection of adverse effects). Before choosing amiodarone for the treatment of atrial fibrillation, clinicians should consider other options.
Contraindications
Before initiating treatment with amiodarone, it is critical to establish therapeutic anticoagulation, because the potential exists for conversion to sinus rhythm (with a consequent risk of thromboembolism) at any point during the drug-loading phase. anticoagulation for 3 consecutive weeks or a transesophageal echocardiogram demonstrating the absence of left atrial thrombus. The use of amiodarone in combination with other antiarrhythmic drugs has not been thoroughly studied.
Dronedarone is a new antiarrhythmic agent pharmacologically related to amiodarone but developed to reduce the risk of side effects. Dronedarone is a benzofuran derivative with an electropharmacologic profile closely resembling that of amiodarone but with structural differences intended to eliminate the effects of amiodarone on thyroid and pulmonary functions. In addition, the elimination half-life of dronedarone is 1 to 2 days, as compared with 30 to 55 days for amiodarone.
We investigated the hypothesis that dronedarone is superior to placebo for maintaining sinus rhythm after electrical, pharmacologic, or spontaneous conversion from atrial fibrillation or atrial flutter. ANDROMEDA trial indicates that dronedarone may be associated with an increased risk of death in patients with advanced congestive heart failure and that the drug should not be used in such patients until appropriate data are gathered.
In conclusion, our trials showed that the rates of the first recurrence of atrial fibrillation and of the first symptomatic recurrence at 1 year were significantly reduced with dronedarone, as compared with placebo. Dronedarone also reduced the ventricular rate in atrial fibrillation during recurrences of arrhythmia.
Among patients with stable angina, both those treated with PCI and those treated with optimal medical therapy alone had marked improvements in health status during follow-up. The PCI group had small, but significant, incremental benefits that disappeared by 36 months.
Clinical trials involving patients with chronic coronary artery disease, in contrast to those involving patients with acute coronary syndromes, have not shown that percutaneous coronary intervention (PCI) prevents major cardiovascular events.. The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial compared a strategy of PCI plus optimal medical therapy with optimal medical therapy alone and showed no significant difference in the rate of the primary end point (death or myocardial infarction) during a median follow-up period of 4.6 years. NEJM August 14, 2008
The primary results of the COURAGE trial showed that in patients with stable coronary disease and inducible ischemia who were treated with optimal medical therapy, the addition of PCI did not significantly reduce the risk of death or myocardial infarction. However, therapeutic procedures are performed not only to prevent events but also to improve health status. On the basis of the Seattle Angina Questionnaire analyses, patients had an incremental benefit from PCI for the first 12 to 24 months in the key domains of physical limitations, frequency of angina, and quality of life. A greater benefit from PCI was observed in those patients with more severe and more frequent angina.
ABSTRACT Background Whether bivalirudin is superior to unfractionated heparin in patients with stable or unstable angina who undergo percutaneous coronary intervention (PCI) after pretreatment with clopidogrel is unknown. Methods We enrolled 4570 patients with stable or unstable angina (with normal levels of troponin T and creatine kinase MB) who were undergoing PCI after pretreatment with a 600-mg dose of clopidogrel at least 2 hours before the procedure; 2289 patients were randomly assigned in a double-blind manner to receive bivalirudin, and 2281 to receive unfractionated heparin. The primary end point was the composite of death, myocardial infarction, urgent target-vessel revascularization due to myocardial ischemia within 30 days after randomization, or major bleeding during the index hospitalization (with a net clinical benefit defined as a reduction in the incidence of the end point). The secondary end point was the composite of death, myocardial infarction, or urgent target-vessel revascularization. Conclusions In patients with stable and unstable angina who underwent PCI after pretreatment with clopidogrel, bivalirudin did not provide a net clinical benefit (i.e., it did not reduce the incidence of the composite end point of death, myocardial infarction, urgent target-vessel revascularization, or major bleeding) as compared with unfractionated heparin, but it did significantly reduce the incidence of major bleeding.
The ankle brachial index is the ratio of systolic blood pressures measured at the ankle or foot and the upper arm. A low index suggests generalised arterial disease and could be a useful predictor of cardiovascular risk, according to a meta-analysis of 16 cohort studies. In an analysis of 24 955 men and 23 339 women, adding the ankle brachial index to the traditional Framingham risk score changed risk predictions for about one in five men and about one in three women. In general, men went down a risk category and women went up.
BMJ. 2008 July
Ankle brachial index (ABI )a useful addition to the Framingham risk score
A low ankle brachial index (≤0.9) was a powerful and independent predictor of death, death from cardiovascular disease, and coronary events in both men and women who had no evidence of heart disease at baseline. A particularly high reading (>1.4), was also associated with increased risk, relative to the “normal”
ABI determination by pulse palpation or automatic BP devices are poorly reliable compared with Doppler, and may lead to ABI underestimation for the former and overestimation for the latter. The use of a (portable) Doppler is required for accurate ABI determination.
We performed symptom-limited exercise testing mostly by using the Bruce and modified Bruce protocols; protocol selection was based on aiming for a test that would last 8 to 12 minutes. We estimated exercise capacity in metabolic equivalents, where 1 metabolic equivalent is an oxygen consumption of 3.5 mL per kg of body weight per minute, and calculated the age- and sex-adjusted proportion of predicted exercise capacity achieved by using previously published regression equations .
We measured ST-segment deviation to the nearest 0.5 mm and considered it abnormal if horizontal or sloping away from the isoelectric line at least 80 ms after the J point in at least 2 contiguous leads for at least 3 consecutive beats was observed. We recorded exercise-induced angina as being test-limiting or non–test-limiting.
The Duke treadmill score was calculated as follows: (Bruce equivalent number of minutes until test termination) – (5 x the amount of ST-segment deviation in millimeters) – (4 x the angina index). ST-segment deviation had to be horizontal or sloping away from the isoelectric baseline. The angina index had a value of 0 if no angina occurred during exercise, 1 if non–test-limiting angina occurred, and 2 if test-limiting angina occurred. A score of 5 or greater was considered low risk; between 5 and –10, intermediate risk; and less than –10, high risk.
Myocardial blush grade MBG is a strong angiographic predictor of mortality in patients with TIMI 3 flow after primary angioplasty. The combined incidence of death and nonfatal recurrent myocardial infarction was 33% in the group with MBG 0 or 1 and 21% in the patient group with MBG 2 or 3 Enzymatic infarct size is larger and residual left ventricular ejection fraction is lower in patients with MBG 0 or 1 compared with MBG 2 or 3. Angiographic definition of successful reperfusion should include both TIMI 3 flow as well as MBG 2 or 3.
Angiographic Assessment of Reperfusion in Acute Myocardial Infarction by Myocardial Blush Grade
Angiographic definition of successful reperfusion should include both TIMI 3 flow as well as MBG 2 or 3.
when TIMI 3 flow is achieved, some patients have less optimal reperfusion at the myocardial tissue level, and several mechanisms have been suggested to be involved as, among others, no reflowand distal embolization Therefore, other predictors related to epicardial reperfusion as well as myocardial reperfusion are necessary. We previously described the myocardial blush grade (MBG) after primary angioplasty as an important predictor of infarct size and survival. Infarct size was measured by the cumulative enzyme release for 48 hours and residual ejection fraction.
2003 American Heart Association
Patients who received aprotinin (Trasylol) to mitigate bleeding during (CABG) alone on the day of surgery had a higher mortality than patients who received aminocaproic acid alone .Concerns about the potential intravascular thrombosis
Is ventilation of the lungs necessary when starting cardiopulmonary resuscitation (CPR) for out of hospital cardiac arrest? Increasing evidence shows that it has no effect on outcome and may even make matters worse. The American Heart Association has responded to this controversy by publishing a statement "Hands-only (compression-only) CPR: a call to action for bystander response to adults who experience out-of-hospital sudden cardiac arrest." The main message of this statement is that by encouraging bystanders to provide at least chest compressions, the odds of survival from out of hospital cardiac arrest will be improved .
The administration of cyclosporine at the time of reperfusion was associated with a reduction in infarct size as measured by the release of creatine kinase and delayed hyperenhancement on MRI. Release of troponin I, however, was not significantly reduced by the administration of cyclosporine. These data are preliminary and require confirmation in a larger clinical trial.
Myocardial infarction is a disabling disease that is common in the United States, with more than 1.5 million new cases diagnosed each year. Infarct size is a major determinant of mortality in myocardial infarction. Limitation of infarct size has therefore been an important objective of strategies to improve outcomes. Currently, the most effective way to limit infarct size is to reperfuse the jeopardized myocardium as soon as possible with the use of coronary angioplasty or thrombolysis and to prevent reocclusion of the coronary artery with the use of antiplatelet therapy.
Although reperfusion is undoubtedly beneficial, it has detrimental effects, including myocardial stunning, ventricular arrhythmias, and microvascular dysfunction. Accumulating evidence suggests that reperfusion may also cause irreversible myocardial injury, possibly through a form of mitochondrial dysfunction . The opening of a nonspecific high-conductance channel (called the mitochondrial permeability-transition pore) in the inner mitochondrial membrane results in the collapse of the membrane potential, the uncoupling of the respiratory chain, the efflux of cytochrome c and other proapoptotic factors, and the hydrolysis rather than synthesis of ATP; these metabolic alterations may lead to cardiomyocyte death.
Calcium overload and excessive production of reactive oxygen species in the early minutes of reflow trigger the opening of the mitochondrial permeability-transition pore. In addition to its well-known immunosuppressive properties, cyclosporine is a potent inhibitor of mitochondrial permeability transition, and several reports indicate that it can limit ischemia–reperfusion injury under experimental conditions. NEJMJuly 31, 2008
Results of a three year study involving 2400 patients treated in 10 hospitals across England show that primary angioplasty is feasible and cost effective. Provided that the procedure is carried out within two hours of a heart attack, death rates are lower than with thrombolysis, the current standard treatment, and hospital stays are shorter, says a report of the study. Roger Boyle, England’s clinical director for heart disease and stroke, said that the 30 day mortality rate for thrombolysis is 7%, but this reduces to 5% for angioplasty if it is given within two hours.
In some parts of the country, such as London, regional death rates have been reduced to 3-4%. Routine use of angioplasty after myocardial infarction will save around 240 more lives each year, reduce the recurrence of heart attacks, and prevent about 260 strokes a year, clinical evidence shows.
BMJ 20 October 2008
When it comes to heart attacks and strokes, men and women are not created equal. Women develop cardiovascular disease later than men -- usually after menopause, and often well into their 70s. And women are different from men when it comes to the response to aspirin as well, says Nanette Wenger, MD, spokesperson for the American Heart Association. Based on study data: For healthy men aspirin seems to prevent heart attacks, but not strokes. For healthy women under 65, aspirin prevents strokes, but not heart attacks. For healthy women over 65, aspirin appears to prevent heart attacks similarly to men.acts by reducing the heart rate in a mechanism different from beta blockers and calcium channel blockers, two commonly prescribed antianginal drugs. It is classified as a cardiotonic agent. Ivabradine acts on the If (f is for "funny", so called because it had unusual properties compared with other current systems known at the time of its discovery) ion current, which is highly expressed in the sinoatrial node. If is a mixed Na+–K+ inward current activated by hyperpolarization and modulated by the autonomic nervous system.
It is one of the most important ionic currents for regulating pacemaker activity in the sinoatrial (SA) node. Ivabradine selectively inhibits the pacemaker If current in a dose-dependent manner. Blocking this channel reduces cardiac pacemaker activity, slowing the heart rate and allowing more time for blood to flow to the myocardium . approved by the European Medicines Agency in 2005.
It is indicated for the symptomatic treatment of stable angina pectoris in patients with normal sinus rhythm, who have a contraindication to or intolerance to beta blockers. It has been shown to be non-inferior to the beta-blocker atenolol for this indication and amlodipine. Apart from angina, it is also being used off-label in the treatment of inappropriate sinus tachycardia .
A dose of 5 mg twice daily is recommended initially; after 1 month, it is recommended to increase to 7.5 mg twice daily to get the optimal efficacy linked to heart rate reduction. Given limited experience in the elderly, the manufacturer recommends a starting dose of 2.5 mg .
Treatment with ivabradine lowered heart rate among patients with heart failure but had no impact on cardiac related events, a major clinical trial revealed. "In patients with coronary artery disease and left ventricular dysfunction, treatment with ivabradine was not shown to improve the primary composite endpoint of cardiovascular mortality, hospitalization for myocardial infarction, and heart failure," said Kim Fox, M.D., professor of clinical cardiology at Royal Brompton Hospital, London. Dr. Fox presented the results of the BEAUTIFUL (morBidity-mortality EvAlUaTion of the If inhibitor ivabradine in patients with CAD and left ventricULar dysfunction) trial at the European Society of Cardiology meeting.
14.5% of all patients taking ivabradine experience luminous phenomena (by patients described as sensations of enhanced brightness in a fully maintained visual field). This is probably due to blockage of I h ion channels in the retina which are very similar to cardiac If. These symptoms are mild, transient, fully reversible and non-severe. In clinical studies about 1% of all patients had to discontinue the drug because of these sensations, which occurred on average 40 days after commencement of the drug.
Bradycardia (unusually slow heart rate) occurs at 2% and 5% for doses of 7.5 and 10 mg respectively (compared to 4.3% in atenonol).2.6-4.8% reported headaches.Other common adverse drug reactions (1–10% of patients) include first-degree AV block, ventricular extrasystoles, dizziness and/or blurred vision.
Ivabradine is the first agent to lower heart rate by selectively inhibiting the cardiac-pacemaker current responsible for controlling depolarization in the sinus node. The drug's effects are selective to the sinus node, and it has no effect on intracardiac conduction, myocardial contractility, or ventricular repolarization
Ivabradine is contraindicated in sick sinus syndrome, and cannot be used concominantly with inhibitors of CYP3A4 such as azole antifungals such as ketoconazole, macrolide antibiotics, nefazodone and the anti-HIV drugs nelfinavir and ritonavir
쀂җ(쀀џ쀂Ƞē~ǯЂ鰀Ѓ攰‚늘ѓ攰„늘…‡€їƿǿ́Љ̿쎀οRectangle 3ǢМᔬഋl In addition to improving various exercise parameters, ivabradine (Procoralan, Servier) was safe and well tolerated, with no serious adverse events reported, said investigators. Canadian Cardiovascular Congress 2008, lead investigator Dr Jean-Claude Tardif. If a patient has angina and a prior history of myocardial infarction, I would start with a beta blocker," said Tardif. "If I wanted to treat symptoms and to prevent effort-induced angina and the patient had no history of myocardial infarction, I would feel comfortable using a beta blocker, a calcium-channel antagonist, or ivabradine.
The drug's effects are selective to the sinus node, and it has no effect on intracardiac conduction, myocardial contractility, or ventricular repolarization. At four months, treatment with ivabradine significantly increased total exercise duration as well as improved time to limiting angina, time to angina onset, and time to 1-mm ST-segment depression.
Radial-access PCI reduces major bleeding 73% compared with femoral approach In addition to the reduction in major bleeding, there were trends toward a reduction in ischemic events, although these did not reach statistical significance. A second study also showed that radial-access PCI in STEMI patients does not compromise reperfusion times. (Canadian Cardiology Congress 2008.)
Metformin top oral antidiabetic for CV-risk reduction, says meta-analysis Of all such agents used in 40 select clinical trials, only metformin significantly reduced cardiovascular mortality. An accompanying editorial highlights limitations of meta-analyses and the shortfalls in knowledge about the CV effects of these agents. Intern Med 2008; 168:2070-2080.
two studies were conducted: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial.In the ACCORD trial, 10,251 type 2 diabetic patients (mean age, 62; 38% women) were randomized to receive intensive glucose-lowering therapy (target HbA1c, <6.0%) or standard therapy (target HbA1c, 7.0%–7.9%). (JW Cardiol Feb 13 2008).
The primary outcome was a composite of nonfatal MI, nonfatal stroke, and cardiovascular-related death. study was discontinued after 3.5 years of follow-up because of a greater number of deaths among patients receiving intensive therapy than among those receiving standard therapy (257 vs. 203; hazard ratio [HR], 1.22; P=0.04).
These two studies, involving different strategies with different patterns of medication use, fail to support the hypothesis that tight glucose control in patients with type 2 diabetes will reduce their risk for macrovascular complications. Moreover, the strategies were associated with an increased risk for hypoglycemia in both studies and with higher mortality in ACCORD. The lower risk for microvascular complications in ADVANCE (this outcome was not reported in ACCORD) was the only favorable finding.
In one study, sharp or stabbing chest pain was documented in 5% of 104 patients with a final diagnosis of myocardial infarction, and in 17% of 143 with unstable angina
BMJ 17 March 2008
Beta blockers up risk of MI, death after noncardiac ops A new retrospective cohort study has found that those taking beta blockers prior to noncardiac surgery had higher rates of MI and death at 30 days than those not taking beta blockers.
women taking hormones on a cyclical basis (estrogen every day with seven to 10 days of progestogen each month) and those using estrogen transdermal patches or vaginal gels had lower risks of MI than those taking continuous combined estrogen and progestogen therapy, the type of HRT used in the Women's Health Initiative (WHI) trial. The main message is that when HRT is indicated for a woman, then a cyclical combined regimen should be preferred and that application of estrogen via the skin or vagina is associated with the lowest risk of MI .
In all age groups, the highest risk of MI was found with a continuous combined HRT regimen— No increased risk of MI was found with unopposed estrogen, cyclical combined HRT, or tibolone, and a significantly lower risk of MI was found with dermal routes of application. If the method of taking estrogen was via a patch or gel on the skin, the risk of MI was reduced by 38%, and for vaginal application, by 44%, compared with oral unopposed estrogen therapy. There was a significantly decreased risk of MI (RR, 0.62) with dermal unopposed estrogen compared with no HRT use, which was significantly lower than for oral unopposed estrogen use (P = .04).
The highest risk was found for the continuous regimen. Unopposed estrogen use was not associated with increased MI risk. There was a significantly decreased risk of MI (RR, 0.62) with dermal unopposed estrogen compared with no HRT use, which was significantly lower than for oral unopposed estrogen use (.Risk of MI was also lower for vaginal preparations of estrogen. There was no association between estrogen dosage and MI risk. There were no significant interactions between use of hormones and concomitant use of medications for diabetes, rhythm disorder, or hypertension. There was no increased risk of MI with type of estrogen or progestagen used.
September 30, 2008 in the European Heart Journal.
coronary-artery bypass grafting )CABG) has been considered standard therapy for patients with left main coronary artery disease and is recommended by current practice guidelines. Because of concern about procedural risk and long-term durability, percutaneous coronary intervention )PCI) usually has been restricted to patients who are poor candidates for surgery or have left main coronary artery disease that is "protected" by a patent bypass graft to the left anterior descending or circumflex artery.
Interest in stenting of the left main coronary artery has increased further with the availability of drug-eluting stents .The MAIN-COMPARE registry holds data on consecutive patients from 12 major cardiac centers in Korea that performed PCI or CABG for unprotected left main coronary artery disease (defined as stenosis of more than 50%) between January 2000 and June 2006.
In conclusion, we found that in matched cohorts of patients with unprotected left main coronary artery disease, PCI with stenting and CABG were associated with similar long-term rates of death and the composite end point of death, Q-wave myocardial infarction, or stroke. Rates of target-vessel revascularization were higher among patients who underwent PCI than among those who underwent CABG.
PCSK9 loss-of-function allele not only decreases LDL cholesterol levels but also provides protection against myocardial infarction in humans should increase confidence in PCSK9 as a valid target for pharmacologic therapy.
NEJMMay 22, 2008
Timely and effective reperfusion with the use of either primary percutaneous coronary intervention (PCI) or thrombolytic therapy remains the most effective treatment strategy for limiting the size of the myocardial infarct, preserving left ventricular ejection fraction, and improving the clinical outcomes in such patients. However, despite optimal reperfusion therapy, morbidity and mortality remain substantial, with about 5 to 6% of patients having a subsequent cardiovascular event by 30 days. The abrupt reperfusion of ischemic myocardium can itself inflict injury on the myocardium — a phenomenon termed myocardial reperfusion injury.
Experimental studies indicate that this form of myocardial injury accounts for up to 50% of the final size of the infarct, providing an important potential target for protection of the heart. The findings from the study by Piot and colleagues confirm the existence of myocardial reperfusion injury in humans and suggest that the mitochondrial permeability-transition pore is a new target for protecting the heart against this form of injury and reducing the size of the myocardial infarct in patients who are undergoing primary PCI.
Myotonic dystrophy is an autosomal dominant disorder that is the most common muscular dystrophy presenting in adults It is characterized by myotonia (delayed muscle relaxation after contraction), progressive weakness and atrophy of the skeletal muscles, and systemic manifestations, including cardiac involvement.
Sudden death can occur in patients with myotonic dystrophy type 1 as a consequence of myocardial fibrosis and degeneration of the cardiac-conduction system,initially manifests as asymptomatic electrocardiographic (ECG) abnormalities, commonly prolongation of the PR interval and QRS duration. Arrhythmias can occur, including sinus-node dysfunction; progressive heart block; atrial tachycardia, flutter, or fibrillation; and ventricular tachycardia or fibrillation.
The most common clinical arrhythmia observed was an atrial tachyarrhythmia. A diagnosis of atrial tachyarrhythmia was the only characteristic independently predicting both sudden death and death from progressive neuromuscular respiratory failure. Different mechanisms could be responsible for the association of an atrial tachyarrhythmia with these two causes of death. An atrial tachyarrhythmia could reflect the presence of atrial fibrosis indicative of conduction involvement and an increased risk of sudden death. NEJM June 2008
Around 5% of men aged between 65 and 74 have abdominal aortic aneurysms (maximum infrarenal aortic diameter of at least 3 cm). The prevalence is some six times lower in women. overall mortality for ruptured aortic aneurysm in the region of 80%. Conventional open repair of unruptured aneurysms below the renal arteries (95% of the total) carries a mean mortality of 9.5%,5 although recent UK series have reported mortalities of 5.5%, 6%, and 4.2%.
The advantage of having an aneurysm repaired before it ruptures is thus enormous. Abdominal aortic aneurysms can be reliably detected by ultrasonography. screening all men just once, when they reach the age of 65, will be cost effective.
The main objection, however, is that about taking people off the street who think they are perfectly well and subjecting them to a procedure from which 1 in 14 will die,and the cost of dealing with the comorbidity needs to be included in the cost-benefit analysis. We know that aneurysms with a diameter of less than 5.5 cm are so unlikely to burst that the mortality from operating on them is greater than the likelihood of rupture. People who have been screened and found to have an aorta that is dilated less than 5.5 cm will be condemned to six monthly or annual ultrasound examinations to estimate the size of the aneurysm.
Intravenous catheterisation is the most common invasive procedure among patients admitted to hospital, with about half receiving intravenous therapy during their stay. The procedure is not without risks. Between 2.3% and 67% of patients develop thrombophlebitis; the rate depending on definitions used and populations studied. The more serious complication, infection of the bloodstream, occurs in about 0.1% of cases.
We found that about 3% remained trouble free for over seven days and some for as long as two weeks. Because of this we believe that routinely changing catheters may be an unnecessary and painful intervention for patients, and costly for the organisation.
BMJ Jul 19 2008
The overall risk of deep vein thrombosis is higher than 20% after major surgery and higher than 40% in patients having major orthopaedic surgery The most recent review of the evidence was commissioned by the National Institute for Health and Clinical Excellence (NICE) which provides national guidance for clinicians in England and Wales. This study reviewed nine randomised controlled trials with 1344 participants identified in two previous systematic reviews3 4 that compared graduated compression stockings with no prophylaxis and concluded that stockings reduce the risk by 51%.There were too few trials and too few cases reporting pulmonary embolism to assess effects of stocking use on this outcome. The NICE guideline recommends that all patients admitted to hospital for surgery, except those with peripheral arterial disease, should wear graduated compression stockings from the time of admission until they return to their usual level of mobility.
BMJ 2008 (26 April)
1. Transient akinesis or dyskinesis of the left ventricular apical and mid-ventricular segments with regional wall motion abnormalities 2. Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture 3. New electrocardiographic abnormalities (either ST segment elevation or T wave inversion) 4.. Absence of:
Mayo criteria for the clinical diagnosis of tako-tsubo cardiomyopathy
Recent significant head trauma Intracranial bleeding Phaeochromocytoma Obstructive epicardial coronary artery disease Myocarditis Hypertrophic cardiomyopathy
1. tako-tsubo cardiomyopathy, also known as left ventricular apical ballooning and "broken heart syndrome."It was first described in Japan 2. It has been traditionally associated with emotional or physical upset in postmenopausal women. 3. Patients should be treated as for acute myocardial infarction. Many develop symptoms of acute left ventricular failure and should be treated as per current guidelines (nitrates, diuretics, etc). 4. Characteristic findings are: Chest pain or dyspnoea Electrocardiographic changes suggestive of acute myocardial infarction or elevated cardiac troponin Triggered by emotional or physical stress Normal coronary angiogram Characteristic left ventricular apical "ballooning"
The pathophysiology of the condition is as yet uncertain, although there are several theories. It is thought to be a catecholamine mediated injury in the context of low circulating oestrogen, perhaps explaining the prevalence in post-menopausal women—though it is far from exclusive to this group. Catecholamine concentrations are in excess of those seen in comparable acute myocardial infarctions and animal models have shown reversibility of the changes with pretreatment with -adrenoreceptor blockade. The rat model has also shown a protective effect from oestradiol treatment in stress induced cardiomyopathy. Coronary artery vasospasm has been postulated—but the multivessel spasm, which would be required, has been reliably shown in very few patients.
More likely is an abnormality in the microcirculation: measurement of flow rates during early coronary angiography has occasionally shown a reduction. The clinical picture does have similarities to the catecholamine mediated cardiomyopathy found in intracerebral and subarachnoid haemorrhage, also thought to be catecholamine mediated; however in these patients the apex is spared and it is the basal segment of the left ventricle that is hypokinetic.16 Myocarditis can also produce transient regional wall motion abnormalities but viral titres have been consistently negative in these patients.
It is clearly difficult to differentiate between acute myocardial infarction and tako-tsubo cardiomyopathy and the clear consensus is that patients should initially be treated as the former.
Pulmonary oedema due to left ventricular systolic dysfunction is often present and should be treated with supportive measures, nitrates and diuretics. β blockers have shown promise in reversing the "ballooning" of the left ventricle during simulations with dobutamine stress echocardiography and should probably be utilised. Angiotensin converting enzyme (ACE) inhibitors have been anecdotally shown to be effective, although no randomised prospective data yet existThe prognosis is good with return to normal left ventricle function in almost all patients, with recovery of normal performance. The rate of recurrence in the longest follow-up was low, at 11.4% over 4 years. However almost a third of patients had recurrent chest pain. Mortality was no higher than for an equivalent "normal" population.
Learning points Tako-tsubo cardiomyopathy is a differential diagnosis of chest pain . It is most common in postmenopausal women. It mimics acute myocardial infarction . Treatment for ST elevation or non-ST elevation myocardial infarction should not be delayed while considering this diagnosis. It requires coronary angiography to diagnose non-obstructive coronary artery disease. The pathophysiology is unclear—but is likely to be catecholamine mediated.There is no randomised control trial data for its management, which is currently symptomatic.β blockers and ACE inhibitors may be useful.
Sitaxsentan sodium is a small molecule sodium salt that blocks the action of endothelin on the endothelin-A receptor selectively (by a factor of 6000 compared to the ERB), and is undergoing FDA approval for treating pulmonary hypertension. Its main benefit compared to bosentan, a nonselective ER blocker, is expected to be less inhibition of the beneficial effects of ERB stimulation, such as nitric oxide production. Endothelin is a 21-amino acid vasoconstricting peptide that plays a key part in vascular homeostasis. ... Because thelin inhibits metabolism of warfarin, a decreased dose of warfarin is needed when co-administered with thelin.
Bosentan is rated as a pregnancy-risk category X. Mandatory monthly liver function tests are required for safe administration of bosentan, ambrisentan and sitaxsentan, while dose adjustment of warfarin and careful monitoring are required when sitaxsentan is initiated
Some endothelin receptor antagonists (ERAs) are associated with liver function test (LFT) abnormalities. However, ambrisentan has an incidence of serum aminotransferases >3 times the upper limit of normal (ULN) similar to that observed in PAH patients who are not taking ERAs. No additional aminotransferases >3xULN were observed with long-term treatment (median exposure, 102 weeks), despite dose increases to 10 mg once daily in more than half of the patients. Significant improvements in 6MWD and other efficacy assessments were observed. Conclusions Ambrisentan treatment may be an option for patients who have discontinued bosentan and/or sitaxsentan therapy due to LFT abnormalities.
Chest. 2008 Sep 23
Peak oxygen uptake (peak VO2) is a reference parameter in the assessment of functional capacity of patients with chronic heart failure, but the procedure for cardiopulmonary exercise testing with expired gas analysis is complex and expensive, so more simple and available methods are desirable.
Categorization of functional capacity in patients with chronic heart failure (CHF) with the New York Heart Association (NYHA) classification or clinical questionnaires is rather subjective. Determination of peak oxygen consumption (peak VO2) during a cardiopulmonary exercise testing provides an objective and reproducible assessment of functional capacity in these patients. Peak VO2 and percentage of age- and sex-adjusted predicted peak VO2 (%PVO2) are strong survival predictors, and it has been reported that in patients who achieve a peak VO2 >14 mL/kg/min or >50% PVO2, heart transplantation could be safely deferred.
The procedure for cardiopulmonary exercise testing is complex and expensive equipment is required; thus more simple and available methods may have wider applicability. The 6-minute walk test (6-MT) has a moderate but significant correlation with peak VO2 in patients with advanced CHF. a shuttle walk test (SWT) with incremental and progressive structure has been shown to provide an objective measurement test of functional disability.
Multivariate Equations Predicting Peak VO2 and %PVO2
while TN elevation is typically related to myocardial damage, it is not pathognomonic for acute coronary syndrome (ACS). There are actually quite a few other conditions in which TN levels may increase, especially to low or "marginal" levels. It's important for emergency physicians (EPs) to be aware of these conditions so they do not inappropriately treat these patients for ACS.Cardiac TNs are regulatory proteins in striated muscle and consist of 3 subunits: TN-T, TN-I, and TN-C. Striated muscle is present in skeletal and cardiac muscle. TN-C is also found in smooth muscle so it has the least cardiac specificity. In this viewpoint, the term "TN" will refer to TN-I and TN-T, not TN-C. TN-I is considered the most cardiac-specific because it has not been identified in skeletal muscle.
TN-T has been found in low levels in various skeletal muscle disorders. TN-T is also less specific for cardiac disease in the presence of renal failure. TNs may be elevated in the presence of reversible or irreversibly myocyte damage. This may be the result of ACS but also disorders of cardiac inflammation, intoxication, malignancy, or degeneration. For most of the causes of TN elevations, even marginal elevations are usually associated with an increased risk for adverse in-patient events
and all-cause inpatient mortality. The majority of the non-ACS conditions listed below tend to cause rather low-level TN elevations, and usually they do not tend to cause the typical evolving rise-and-fall pattern of TN levels over 12 to 24 hours that are found in patients with true ACS. Therefore, when there is a question regarding whether a patient with an initially elevated TN level has ACS or not, it would be prudent to monitor changes in the electrocardiograph and serial TN levels to help make the distinction
Cardiac Diseases ACS. TN elevation has clearly been shown to correlate with adverse cardiac events as well as short-term and long-term mortality in patients with ACS. TN elevations should prompt more aggressive medical therapy of patients with ACS Congestive heart failure. TN elevations identify high-risk patients with poor short-term prognosis. Elevations are also associated with an increased risk for ventricular dysrhythmias, and when combined with elevations of B-type natriuretic peptide, predict increased inpatient mortality in patients with congestive heart failure (CHF).
Myocarditis and pericarditis. TN elevations are helpful in identifying myocyte necrosis associated with myocarditis, and elevations may also be found with pericarditis. Note that if a patient with pericarditis has TN elevations, it is often assumed that there is myocardial involvement as well (which is thus referred to as myopericarditis). Although TN levels do not correlate with prognosis in these patients, there is a good correlation between TN elevation and1-month duration of heart failure symptoms.
Cardioversion/defibrillation. External or internal cardioversion/defibrillation does not seem to be associated with myocardial injury or "marked" elevations of TN levels. Even if there are more minor elevations of TN purely due to the shock, the levels should be low and should resolve quickly. Higher levels should indicate true acute MI. Cardiac procedures. TN levels may be elevated after a prolonged PCI due to prolonged balloon inflation, but the significance of these levels is uncertain. Perioperative and especially postoperative TN elevations in patients undergoing CABG is associated with prognosis
Cardiac trauma. Patients with TN elevations after blunt cardiac trauma have a higher risk of cardiac dysrhythmias and LV dysfunction. However, their prognosis is unrelated to the level. "Nondetectable TN levels in asymptomatic patients at admission and within the first 6 hours after admission can rule out relevant myocardial injury." As noted below, however, TN elevations in these patients can also occur due to hemorrhage or shock.
Cardiotoxins. Bites by venomous snakes can cause acute MI or vasospasm, resulting in elevated TN levels. This is attributed to the direct myocardial effect of the venom's toxin. The same phenomenon has been reported with jellyfish, scorpion, and certain insect stings. Tachycardia. Severe tachycardia, even in the presence of normal coronary arteries, can induce elevations of TN due to increased myocardial oxygen demand and decreased myocardial oxygen supply
Sepsis. correlate with myocardial dysfunction in patients with critical illness. Postulated mechanisms for this include demand ischemia (due to increased oxygen demand related to increased cardiac output, tachycardia, or use of pressors); release of myocardial depressants (eg, TNF alpha, interleukin 1, interleukin 6); and direct cardiac myocytotoxic effects of endotoxins, cytokines, or reactive oxygen radicals induced by the infectious process. Regardless of the cause, high TN levels predict increased severity of sepsis, prolonged intensive care unit length of stay, and increased mortality.
Pulmonary embolism. TN elevations in patients with pulmonary embolism (PE) predict a complications and mortality. Many propose that TN elevations in the presence of PE may warrant more aggressive therapy, such as thrombolytics, although good outcome studies related to this proposal are lacking. Large PEs induce acute right ventricular pressure overload, which causes increased wall tension and regional wall ischemia. This is proposed as a potential reason for the TN release.
Chronic obstructive pulmonary disease. Severe exacerbations of COPD are associated with acute right ventricular strain and can therefore produce TN release through a similar mechanism as that proposed for PE. Alternatively, patients with (COPD) exacerbations may have concurrent acute MI, CHF, or PE and therefore have elevated TN levels. TN elevations correlate with the severity of the COPD exacerbation and length of hospital stay. Carbon monoxide poisoning. TN elevations may occur in CO poisoning and is likely related to myocardial hypoxia and injury.
Intracranial abnormalities. TN elevations may occur in patients with intracranial (IC) abnormalities due to sympathetic overstimulation and/or altered autonomic tone associated with these disorders. Elevated IC pressure, for example, leads to marked increases in catecholamine output, which induces tachycardia, coronary vasospasm, vasoconstriction, and intracellular calcium increases, which have direct myocardial toxic effects.
Subarachnoid hemorrhage (SAH): Higher Hunt-Hess grade, female gender, larger body surface area, larger left ventricular mass, lower systolic blood pressue (SBP), and higher heart rate in patients with SAH are all predictors of TN elevation. Hypothalamic stress from SAH results in large releases of catecholamines, which may result in myocardial damage. Elevated TN levels in patients with SAH correlate with risk for cardiopulmonary complications, delayed cerebral ischemia, worse functional outcomes at discharge, and death;
Acute ischemic stroke: TN elevation at admission in patients with stroke is associated with increased risk of in-hospital cardiac complications and mortality; IC hemorrhage: TN elevation in patients with IC hemorrhage is an independent predictor of increased in-hospital mortality; and
Epilepsy and seizures: TN levels may be elevated in patients with persistent seizures. Plasma catecholamines can reach 12-40 times normal within minutes in seizing patients. These elevated catecholamine levels in combination with metabolic acidosis, increased oxygen demand, diffuse cerebral stimulation, and cerebral edema can produce TN elevations. Although a direct prognostic value of elevated TN in patients with seizures has not been found, TN elevations should not be ignored: generalized seizures are known to be a significant physiological "stress test" and can induce acute MI in patients with pre-existing coronary disease. Further ACS workup should ensue in these patients.
End-stage renal disease. Patients with end-stage renal disease may have chronically elevated TN levels due to ongoing myocyte damage and "micromyocardial infarction." Even in the absence of acute MI, TN levels may be elevated. Elevated TN-T levels may persist even after hemodialysis in these patients, but the authors state that TN-I should not follow this pattern. TN-I levels should decrease after hemodialysis. Regardless of whether the TN elevations are chronic, any elevation of TN predicts a high risk for overall mortality and major adverse cardiac events at 2 years, even in asymptomatic patients. In acutely ill hemodialysis-dependent patients, an elevated TN level predicts an increased 30-day cardiac risk regardless of the presentation.
Rhabdomyolysis. Emergency department patients presenting with rhabdomyolysis often have positive TN levels. These levels do not correlate well with serum creatine phosphokinase levels, renal failure, degree of muscle damage, or cardiovascular risk factors. The TN levels may be related to the underlying cause of rhabdomyolysis (eg, cocaine toxicity, hypotension, sepsis, etc). Elevated TN levels correlate with hospital length of stay and morbidity.
Eclampsia and preeclampsia. Pregnant women with hypertensive disorders have elevated TN levels. Levels seem to correlate with the presence of proteinuria. Extreme endurance exercise. TN elevations occur in up to one third of individuals participating in prolonged strenuous exercises (eg, marathons, triathlons, etc). There does not seem to be an association with adverse cardiac outcomes in these patients.
Other causes. Some of the other non-ACS conditions listed in the article without discussion that are associated with TN elevations include Upper gastrointestinal bleeding. Left ventricular hypertrophy. Catecholamine toxicity.
When any doctor or nurse refers to a colleague they should automatically ask themselves: is this referral necessary and will it benefit the patient? Referral should never be an automatic choice and the circumstances may dictate a different option.
The clinician needs to ask four principle questions before referral. First: will the referral improve the accuracy of diagnosis and provide better management of the disorder? Second: have all the appropriate examinations and investigations been carried out? The third concerns treatment: all patients should have appropriate treatment initiated as soon as possible as delay can, in many cases, leave them exposed to harm. The fourth principle question is: am I referring this patient to the service or individual who will best help their management?
British Journal of Cardiology 10/31/2008
C-reactive protein (CRP) is a non- specific acute phase protein produced by the liver in response to variety of inflammatory processes High-sensitivity C-reactive protein (hsCRP) levels are an independent marker of cardiovascular disease risk, according to findings from two studies reported at the American Heart Association's Scientific Sessions 2008.
"Many clinicians now offer hsCRP testing to their patients, but until now the value of hsCRP levels to treatment decisions, especially in adults with desirable cholesterol levels, was unclear," she noted. "As part of the NHLBI strategic plan, we have engaged an expert panel to review and update the scientific evidence regarding the assessment and management of cardiovascular risk factors."
Hs -CRP is most often used to help predict a healthy person's risk of cardiovascular disease. People who have hs -CRP results in the high end of the normal range have 1.5 to 4 times the risk of having a heart attack as those with CRP values at the low end of the normal range. The CRP molecule itself is not a harmful molecule in the body. The higher level of CRP is simply a reflection of higher than normal inflammation. The measurement of CRP does not reflect where the inflammation is. It may come from cells in the fatty deposits in arterial walls that reflect the process of atherosclerosis. It may come from other tissues. The AHA/CDC defined risk groups as follows: Low risk: less than 1.0 mg/L Average risk: 1.0 to 3.0 mg/L High risk: above 3.0 mg/L
Because hs-CRP tests are measuring a marker of inflammation, it is important that any person having the test be healthy in order for the test to be of any value in predicting the risk of coronary disease or heart attack. Any recent illness, tissue injury, infection, or general inflammation will raise the amount of CRP and give a falsely elevated estimate of risk.
Should I have my CRP level measured?If a person’s cardiovascular risk score — judged by global risk assessment — is low (the possibility of developing cardiovascular disease is less than 10 percent in 10 years), no test is immediately warranted. If the risk score is in the intermediate range (10–20 percent in 10 years), such a test can help predict a cardiovascular or stroke event and help direct further evaluation and therapy. However, the benefits of such therapy based on this strategy remain uncertain. A person with a high risk score (greater than 20 percent in 10 years) or established heart disease or stroke should be treated intensively regardless of hs -CRP levels.
A cardiovascular event Is defined in the Framingham equation as myocardial infarction, new angina, ischaemic stroke, transient ischaemic attack (TIA), peripheral vascular disease (PVD), congestive heart failure (CHF) and cardiovascular-related death.
False-Positive Results TN elevation As with any test, there is the potential for false-positive results. These results can occur "due to cross-reaction with other plasma components such as high serum levels of free hemoglobin or bilirubin or to interference with autoantibodies [against the TN complex], heterophilic antibodies, or rheumatoid factor. Fibrin residuals and other microparticles can also interfere with TN determinations.”Medscape Emergency Medicine. 2008
November 12, 2008 (New Orleans, Louisiana) — Early invasive management—angiography within 24 hours followed by percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) as appropriate—is safe in patients with unstable angina or non-ST-segment-elevation MI (NSTEMI) but overall has the same impact on the risk of death, new myocardial infarction (MI), or stroke compared with a delayed invasive strategy, concluded a randomized trial reported here at the American Heart Association 2008 Scientific Sessions .
The early strategy did, however, reduce the risk of refractory ischemia compared with delayed management, which the trial, called Timing of Intervention in Patients with Acute Coronary Syndromes (TIMACS), defined as occurring after at least 36 hours. Importantly, early management in TIMACS also significantly cut the risk of death or cardiovascular (CV) events among patients who were judged to be at high risk based on their GRACE scores, which stratify risk status as low, intermediate, or high . Among the study's messages, according to its investigators and observers at the meeting, are that high-risk patients should definitely get early invasive management, while low- to moderate-risk patients can go either way, depending on the circumstances.
Most patients with acute coronary syndromes can be managed safely with either an early or a delayed invasive strategy," Dr Shamir R Mehta (McMaster University, Hamilton, ON) said when presenting the TIMACS study. "However, in a subset of patients at highest risk, early intervention appears to be superior, and these patients should be considered for early heart catheterization. In all other patients with acute coronary syndromes, the decision regarding the timing depends on other factors, such as cath -lab availability, the healthcare system environment, convenience, and economic considerations. *Low/intermediate risk=GRACE score <140; high risk=GRACE score ≥140
TIMACS randomized more than 3000 patients with unstable angina or NSTEMI who were "suitable" for revascularization to early (angiography as soon as possible within 24 hours, followed by PCI or CABG) or delayed (any time after 36 hours, followed by PCI or CABG) invasive management.
Aspirin and clopidogrel are irreversible inhibitors of platelet activation and, with the exception of neurosurgery, combined therapy seems to increase surgical bleeding by about 50% without affecting morbidity or mortality. The risks and consequences of excess bleeding should be carefully considered before discontinuing dual antiplatelet therapy. Dual antiplatelet therapy need not be interrupted for dental or minor surgical procedures.
Where therapy must be discontinued prematurely to minimise the operative bleeding risk during major surgery, trial data suggest that this should be done at least five days before surgery. Aspirin should be continued perioperatively if possible and clopidogrel restarted at the earliest opportunity after surgery.
A cardiologist must be involved in any decision to discontinue antiplatelet therapy prematurely in patients with a recently implanted coronary stent. In patients at high risk of perioperative stent thrombosis in whom an interruption in dual antiplatelet therapy is unavoidable, "bridging" therapy with heparin, direct thrombin, or short acting intravenous glycoprotein IIb/IIIa inhibitors until oral antiplatelet agents can be safely restarted should be considered, although the success of this approach is unclear. For such patients, it might be safest to perform surgery in centres with rapid access to emergency percutaneous coronary intervention.
November 2008 BMJ
Automaticity Generates electrical impulse independently,without involving the nervous system. Excitability Responds to electrical stimulation. Conductivity Passes or propagates electrical impulses from cell to cell. Contractility Shortens in response to electrical stimulation.
Physical activity is anything that gets your body moving. According to the 2008 Physical Activity Guidelines for Americans, you need to do two types of physical activity each week to improve your health–aerobic and muscle-strengthening. How much physical activity do adults need?
10 minutes at a time is fine We know 150 minutes each week sounds like a lot of time, but it's not. That's 2 hours and 30 minutes, about the same amount of time you might spend watching a movie. The good news is that you can spread your activity out during the week, so you don't have to do it all at once. You can even break it up into smaller chunks of time during the day. It's about what works best for you, as long as you're doing physical activity at a moderate or vigorous effort for at least 10 minutes at a time.
Aerobic activity – what counts? Aerobic activity or "cardio" gets you breathing harder and your heart beating faster. From pushing a lawn mower, to taking a dance class, to biking to the store – all types of activities count. As long as you're doing them at a moderate or vigorous intensity for at least 10 minutes at a time. Even something as simple as walking is a great way to get the aerobic activity you need, as long as it's at a moderately intense pace.Intensity is how hard your body is working during aerobic activity.How do you know if you're doing moderate or vigorous aerobic activity?
On a 10-point scale, where sitting is 0 and working as hard as you can is 10, moderate-intensity aerobic activity is a 5 or 6. It will make you breathe harder and your heart beat faster. You'll also notice that you'll be able to talk, but not sing the words to your favorite song. Here are some examples of activities that require moderate effort: Walking fast Doing water aerobics Riding a bike on level ground or with few hills Playing doubles tennis Pushing a lawn mower
Vigorous-intensity aerobic activity means you're breathing hard and fast, and your heart rate has gone up quite a bit. If you're working at this level, you won't be able to say more than a few words without pausing for a breath. Here are some examples of activities that require vigorous effort: Jogging or running Swimming laps Riding a bike fast or on hills Playing singles tennis Playing basketball You can do moderate- or vigorous-intensity aerobic activity, or a mix of the two each week. A rule of thumb is that 1 minute of vigorous-intensity activity is about the same as 2 minutes of moderate-intensity activity.
Some people like to do vigorous types of activity because it gives them about the same health benefits in half the time. If you haven't been very active lately, increase your activity level slowly. You need to feel comfortable doing moderate-intensity activities before you move on to more vigorous ones. The guidelines are about doing physical activity that is right for you.
Besides aerobic activity, you need to do things to strengthen your muscles at least 2 days a week. These activities should work all the major muscle groups of your body (legs, hips, back, chest, abdomen, shoulders, and arms). To gain health benefits, muscle-strengthening activities need to be done to the point where it's hard for you to do another repetition without help. A repetition is one complete movement of an activity, like lifting a weight or doing a sit-up. Try to do 8—12 repetitions per activity that count as 1 set. Try to do at least 1 set of muscle-strengthening activities, but to gain even more benefits, do 2 or 3 sets.
You can do activities that strengthen your muscles on the same or different days that you do aerobic activity, whatever works best. Just keep in mind that muscle-strengthening activities don't count toward your aerobic activity total. There are many ways you can strengthen your muscles, whether it's at home or the gym. You may want to try the following: Lifting weights Working with resistance bands Doing exercises that use your body weight for resistance (i.e., push ups, sit ups) Heavy gardening (i.e., digging, shoveling) Yoga
Muscle-strengthening activities – what counts?For more information about strength training, visit Growing Stronger: Strength Training for Older Adults.Besides aerobic activity, you need to do things to make your muscles stronger at least 2 days a week. These types of activities will help keep you from losing muscle as you get older.
To gain health benefits, muscle-strengthening activities need to be done to the point where it's hard for you to do another repetition without help. A repetition is one complete movement of an activity, like lifting a weight or doing one sit-up. Try to do 8—12 repetitions per activity that count as 1 set. Try to do at least 1 set of muscle-strengthening activities, but to gain even more benefits, do 2 or 3 sets.
Acute pericarditis may occur as an isolated entity or as the result of a systemic disease. The incidence is estimated to be about 5% of ED patients with chest pain but without myocardial infarction. Most cases are idiopathic in origin; however, the clinician must also consider infectious, neoplastic, autoimmune, uremic, radiation-induced, postischemic, postvaccine, and traumatic etiologies.
Important conditions that may cause chest pain similar to that of pericarditis include myocardial infarction, pulmonary embolism, aortic dissection, pleural effusion, and pneumomediastinum.
The typical history consists of chest pain that is sudden in onset and pleuritic in nature. It is usually more intense when the patient is supine and improves when he or she sits upright and leans forward. The pain often radiates to the neck, arm, shoulder, and/or trapezius ridge because the phrenic nerve (which innervates the trapezius) traverses the pericardium.
The physical examination may reveal a high-pitched scratchy or squeaky friction rub best heard at the left sternal border at end expiration when the patient is leaning forward. vary in intensity from minute to minute, should have cardiac auscultation repeated multiple times having three components, which correspond to atrial systole, ventricular systole, and rapid ventricular filling during early diastole. distinguished from a pleural rub by the fact that it can be heard even when respirations are suspended.
Pericardial effusions are common sequelae. The presence of hypotension, tachycardia, elevated jugular venous pressure, and/or pulsus paradoxus (a decrease in systolic arterial pressure of more than 10 mm Hg with inspiration) suggests the development of a pericardial effusion and cardiac tamponade.
Stage I- Diffuse ST-segment elevation and PR-segment depression Stage II- Normalization of the ST and PR segments, with flattening of the T wave Stage III- Widespread T-wave inversions Stage IV- Normalization of the T waves
The ECG abnormalities may evolve through 4 phases
The prompt institution of therapy may prevent the appearance of all 4 stages. Nonetheless, the changes in stage I are observed in 60-80% of patients with pericarditis. In myocardial infarction, the ST-segment elevations are often convex (domeshaped) rather than concave in configuration, and they are often associated with Q-wave formation and the loss of R-wave voltage. PR-segment depression is not common.
The most reliable distinguishing feature may be the ratio of ST-segment elevation (in mm) to T-wave amplitude (height in mm) in lead V6. When this ratio exceeds 0.24, acute pericarditis is almost always present.
chest radiography are usually normal, may reveal cardiomegaly when there is a large pericardial effusion. Most importantly, radiography may help to provide diagnostic information regarding the likelihood of other conditions, such as pneumothorax, pneumomediastinum, pneumonia, or aortic dissection. (WBC) count, (ESR), (CRP) concentration are usually all elevated in patients with acute pericarditis; however, they are of little utility for determining the etiology for the disease.
Antinuclear and rheumatoid factor antibodies are seen in 10-15% of cases. Viral cultures and antibody titers are not clinically useful. Plasma troponin concentrations are elevated in 35-50% of patients with pericarditis; this finding is thought to be caused by epicardial inflammation rather than myocyte necrosis, although the long-term risk of troponin elevation in acute pericarditis is not clear. The concentration usually returns to normal within 1-2 weeks after the diagnosis.
Transthoracic echocardiography is recommended in all patients with suspected pericarditis because the presence of an effusion helps to confirm the diagnosis, and the clinical or echocardiographic evidence of tamponade indicates the need for therapeutic pericardiocentesis. Pericardiocentesis is indicated in patients with pericardial tamponade and in those with known or suspected purulent or neoplastic pericarditis. When pericardiocentesis is performed, the fluid should be analyzed for red and white blood cell counts, cytologic evidence of cancer, and triglycerides (which are elevated in patients with chylous effusion). The fluid should be cultured as well as examined microscopically.
of pericarditis not complicated by tamponade depends on whether any primary cause is identified or highly suspected. Therapy for patients with idiopathic pericarditis is aimed at the relief of chest pain and inflammation. The treatment has not been shown to prevent tamponade or long term complications such as constrictive pericarditis or recurrent pericarditis.
Although nonsteroidal anti-inflammatory drugs (NSAIDs) are the traditional mainstay of therapy, recent data suggest that colchicine, administered at a dose of 0.6 mg twice daily for 90 days, is more likely to prevent recurrent idiopathic pericarditis. Aspirin (2-4 g daily), indomethacin (75-225 mg daily), or ibuprofen (1600-3200 mg daily), however, are still often prescribed. Colchicine is also preferred for patients who have recurrent pericarditis. Typically, symptoms will improve within days of the initiation of anti-inflammatory therapy.
If chest pain persists after 2 weeks of treatment, a different agent or combination therapy should be considered. If a patient continues to have chest pain despite combination therapy, glucocorticoids should be considered. There is data to suggest, however, that the use of steroids is associated with a higher risk of later recurrence. Patients with a relapse of pericarditis after a short-term course of low-dose glucocorticoid therapy often obtain symptomatic relief when higher-dose prednisone therapy (1-1.5 mg per kilogram of body weight daily) is administered for 4 weeks. Therapy for secondary pericarditis is targeted at the primary cause.
2008 Medscape.
How attractive to have a syndrome where the clinical findings are "right" and the tests are "wrong." In heart failure with normal ejection fraction (HEFNEF), the presentation is consistent with heart failure but echocardiography does not fully agree.The typical image of a patient with heart failure is of a breathless person with a large flabby heart, which contracts poorly with a reduced left ventricular ejection fraction. However, many patients, mainly elderly women, have symptoms of heart failure but their hearts are not enlarged. Echocardiography shows a relatively normal left ventricular ejection fraction but usually with some left ventricular hypertrophy. Because systolic function was thought to be normal or near normal, the term "diastolic heart failure" was coined for this group of patients. However, we now know that systolic function is not entirely normal, and the problem is not only caused by diastolic dysfunction; hence the term "heart failure with a normal ejection fraction" is more appropriate.
In contrast to systolic heart failure, where an echocardiogram can easily show a dilated ventricle and reduced left ventricular ejection fraction, the lack of good non-invasive indices of diastolic function makes heart failure with a normal ejection fraction more difficult to diagnose.
Recent European Society of Cardiology guidelines suggested a diagnostic algorithm for heart failure with a normal ejection fraction. In essence, if a breathless patient has left ventricular hypertrophy, left atrial enlargement, and evidence of a raised left atrial pressure either by B-type natiuretic peptide (which is especially useful in primary care) or newer echocardiographic indices then the diagnosis of heart failure with a normal ejection fraction is highly likely.
The pathophysiology behind the symptoms is complex, and not only diastolic abnormalities are involved. In the normal heart, left ventricular twist during systole (which stores energy), motion of the mitral annulus towards the apex during systole (which also helps suck blood into the atrium), and the corresponding untwisting process and recoil in early diastole when that energy is released to generate the negative intraventricular pressure gradient or suction in early diastole, are tightly coordinated both temporally and functionally.
This process is followed by the rapid motion of the mitral annulus back towards the base of the heart, which also aids ventricular filling by moving the mitral annulus around the column of the incoming blood. All these aspects of ventricular function increase on exercise, not only to accelerate ventricular ejection, but more importantly to enable rapid filling of the ventricle during a shortened diastole while maintaining a low filling pressure. In patients with heart failure and a normal ejection fraction, this close relation between systole and diastole is disrupted.
Recent studies have shown a variety of abnormalities of systolic and diastolic function—reduced myocardial systolic strain, reduced ventricular systolic rotation at rest (which fails to increase normally on exercise), reduced mitral annular motion in systole and diastole, and delayed ventricular untwisting associated with reduced left ventricular suction. Other factors are also involved, such as increased arterial stiffness, which affects ventricular function, and impaired heart rate responses to exercise, similar to patients with systolic heart failure.
Thus, both systolic heart failure and heart failure with a normal ejection fraction have systolic and diastolic functional abnormalities to various degrees and differ mainly by ventricular size. This is probably because infarction—the most common cause of systolic heart failure—is a powerful remodelling stimulus, whereas with hypertension and diabetes—the main causes of heart failure with a normal ejection fraction—the remodelling process is slower and initially hypertrophy occurs without chamber dilatation. However, hypertension can eventually produce ventricular dilatation and typical systolic heart failure if poorly treated.
Few large scale trials have been conducted in heart failure with a normal ejection fraction because in the early trials of heart failure a reduced left ventricular ejection fraction was a prerequisite for entry. However, one trial found that the angiotensin receptor antagonist candesartan modestly reduced hospital admissions for heart failure but did not significantly affect mortality in patients with heart failure with a normal ejection fraction. However, a small randomised controlled trial found that diuretics alone reduced symptoms and improved quality of life significantly, but that adding ramipril or irbesartan was not more efficacious.
Fibrosis and altered collagen in left ventricular hypertrophy may have a deleterious effect on overall myocardial architecture, particularly ventricular twist and torsion. Nevertheless, the reduction of fibrosis may be an important therapeutic target, and the ongoing studies of spironolactone in heart failure with a normal ejection fraction will be interesting.
In summary, heart failure with a normal ejection fraction is a mixed bag of differing pathologies and aetiologies that in combination cause the elderly heart to fail. Despite being common, this type of heart failure is often not recognised, and evidence based treatment—apart from diuretics for symptoms—is lacking. 27 January BMJ 2009
Ventricular remodeling (or cardiac remodelling) refers to the changes in size, shape, and function of the heart after injury to the ventricles. The injury is typically due to acute myocardial infarction (usually ST segment elevation infarction), but may be from a number of causes that result in increased pressure or volume overload (forms of strain) on the heart. Chronic hypertension, congenital heart disease with shunt , and valvular heart disease may also lead to remodeling. After the insult occurs, a series of histopathological and structural changes occur in the left ventricular myocardium that lead to progressive decline in left ventricular performance. Ultimately, ventricular remodeling may result in diminished contractile (systolic) function and reduced stroke volume.
Medically speaking, "ventricular remodeling" implies a decline in function (even though the word "remodeling" usually implies improvement). The term reverse remodeling in cardiology implies an improvement in ventricular mechanics and function after a remote injury. Concentric hypertrophy is due to pressure overload, while eccentric hypertrophy is due to volume overload
Concentric hypertrophy is due to pressure overload, eccentric hypertrophy is due to volume overload
The cardiac myocyte is the major cell involved in remodeling. Fibroblasts, collagen, the interstitium, and the coronary vessels to a lesser extent, also play a role. A common scenario for remodeling is after myocardial infarction. There is myocardial necrosis (cell death) and disproportionate thinning of the heart. This thin, weakened area is unable to withstand the pressure and volume load on the heart in the same manner as the other healthy tissue. As a result there is dilatation of the chamber arising from the infarct region. The initial remodeling phase after a myocardial infarction results in repair of the necrotic area and scar formation that may, to some extent, be considered beneficial since there is an improvement in or maintenance of LV function and cardiac output.
Over time, however, as the heart undergoes ongoing remodeling, it becomes less elliptical and more spherical. Ventricular mass and volume increase, which together adversely affect cardiac function. Eventually, diastolic function, or the heart's ability to relax between contractions may become impaired, further causing decline .
Many factors influence the time course and extent of remodeling, including the severity of the insult, secondary events (recurrent ischemia or infarction), neurohormonal activation, genetic factors and gene expression, and treatment. Medications may attenuate remodeling. Angiotensin-converting enzyme (ACE) inhibitors have been consistently shown to decrease remodeling in animal models or transmural infarction and chronic pressure overload.
Clinical trials have shown that ACE inhibitor therapy after myocardial infarction leads to improved myocardial performance, improved ejection fraction, and decreased mortality compared to patients treated with placebo. Likewise, inhibition of aldosterone, either directly or indirectly, leads to improvement in remodeling. Early correction of congenital heart defects, if appropriate, may prevent remodeling, as will treatment of chronic hypertension or valvular heart disease. Often, reverse remodeling, or improvement in left ventricular function, will also be seen.
stroke volume, the volume of blood ejected with each beat. Ejection fraction (Ef) is the fraction of the end-diastolic volume that is ejected out of a ventricle with each beat. The term ejection fraction applies to both the right and left ventricles; one can speak equally of the left ventricular ejection fraction (LVEF) and the right ventricular ejection fraction (RVEF). Without a qualifier, the term ejection fraction refers specifically to that of the left ventricle.
By definition, the volume of blood within a ventricle immediately before a contraction is known as the end-diastolic volume. Similarly, the volume of blood left in a ventricle at the end of contraction is end-systolic volume. The difference between end-diastolic and end-systolic volumes is the stroke volume, the volume of blood ejected with each beat. Ejection fraction (Ef) is the fraction of the end-diastolic volume that is ejected with each beat; that is, it is stroke volume (SV) divided by end-diastolic volume (EDV):
In a healthy 70-kg (154-lb) man, the SV is approximately 70 ml and the left ventricular EDV is 120 ml, giving an ejection fraction of 70/120, or 0.58 (58%).
Right ventricular volumes being roughly equal to those of the left ventricle, the ejection fraction of the right ventricle is normally equal to that of the left ventricle within narrow limits. Healthy individuals typically have ejection fractions between 50% and 65%
Ejection fraction is commonly measured by echocardiography, in which the volumes of the heart's chambers are measured during the cardiac cycle. Ejection fraction can then be obtained by dividing stroke volume by end-diastolic volume as described above. Other methods of measuring ejection fraction include cardiac MRI,, fast scan cardiac computed axial tomographyimaging, ventriculography,Gated SPECT, and the MUGA scan. A MUGA scan involves the injection of a radioisotope into the blood and detecting its flow through the left ventricle. The historical gold standard for the measurement of ejection fraction is ventriculography.
Systolic dysfunction was defined as an LVEF <40% or qualitative documentation of systolic dysfunction, while preserved systolic function meant LVEF >40% or qualitative documentation of preserved systolic function.
Clearly, there is powerful evidence for significant benefit from certain beta blockers in systolic heart failure But are not the answer for heart failure with preserved systolic function--although such patients may find them beneficial if they also have diabetes, hypertension, or other indications for the drugs. also no effect on mortality or CV events from the angiotensin-receptor blocker irbesartan over a four-year follow-up of patients with heart failure and preserved systolic function. Such patients typically account for about half of all heart failure in most reports.
2009 Medscape
The study, published in the January 26, 2009 issue of the Archives of Internal Medicine, shows dose-related increases in risk of death and rehospitalization for heart failure or MI with all COX-2 inhibitors or other NSAIDs. And it is not just the COX-2 inhibitors that are the problem, as diclofenac showed a similar risk. "This is very disturbing, as this drug is so widely used and is available off prescription in many countries the effect is "quite considerable."
For example, for rofecoxib (Vioxx, Merck), the number of patients needed to treat for one year to cause one death was just nine, and the corresponding number for celecoxib (Celebrex, Pfizer) was 14 and diclofenac 11. "These numbers are very low," Gislason said, noting that for antihypertensive drugs, the number needed to treat for one year to save one life is in the range of 50 to 100. "Everyone agrees that it is worth treating hypertension. So the harmful effect of some NSAIDs is much greater than the beneficial effect of antihypertensive treatment. "even naproxen at high doses. Naproxen is probably the best of the bunch, but it still increases fluid retention, which is bad news for heart-failure patients," Gislason added. .
But he points out that these drugs are still being used in this population. "I don't think doctors are aware of this problem. We need to raise awareness. The authors conclude that patients with heart failure should, if possible, avoid using NSAIDs, and if they do need to use one, they should take an agent that is more COX-1 selective, in as low a dosage and for as short a period as possible. "I know NSAIDs are useful drugs, and they will always be used to some extent, but we need to be careful about which drug is selected and which dosage used.
There is good evidence that NSAIDs, particularly selective COX-2 inhibitors, may promote higher rates of cardiovascular disease. A scientific statement from the American Heart Association, which was published in the March 27, 2007, issue of Circulation, suggests that patients with existing cardiovascular disease or at high risk for coronary heart disease receive acetaminophen or aspirin as their initial treatment of musculoskeletal pain. Nonacetylated salicylates are the next medications to consider in their treatment algorithm. Only when these treatments have failed should the clinician consider prescribing NSAIDs, and the first choice among these NSAIDs are drugs that do not select for COX-2.
A previous recommendation suggested that patients with known cardiovascular disease receive the following treatment algorithm for musculoskeletal pain: acetaminophen or aspirin → nonacetylated salicylates → nonselective NSAIDs → COX-2 inhibitors. In the current study, the use of NSAIDs increased the risks for overall mortality, hospitalization because of heart failure, and hospitalization because of MI in patients with existing heart failure.
The Canadian Association of Gastroenterology convened a panel of 21 physician-experts to develop evidence-based recommendations for long-term (>4 weeks) NSAID use. The panel’s consensus document included the following recommendations: Patients with low GI and low CV risks should receive a traditional NSAID.Patients with low GI and high CV risks should receive naproxen.Patients with high GI and low CV risks should receive a cyclooxygenase-2 inhibitor plus a proton-pump inhibitor.Patients with high GI and high CV risks should receive a careful assessment to prioritize risks.NSAIDs should be prescribed at the lowest effective dose and for the shortest possible duration. Published in Journal Watch Gastroenterology April 10, 2009
Myocarditis may present with a wide range of symptoms, ranging from mild dyspnea or chest pain that resolves without specific therapy to cardiogenic shock and death. Dilated cardiomyopathy with chronic heart failure is the major long-term sequela of myocarditis.
April 9, 2009 NEJM
Most often, myocarditis results from common viral infections; less commonly, specific forms of myocarditis may result from other pathogens, toxic or hypersensitivity drug reactions, giant-cell myocarditis, or sarcoidosis. The prognosis and treatment of myocarditis vary according to the cause, and clinical and hemodynamic data usually provide guidance to decide when to refer a patient to a specialist for endomyocardial biopsy.
The standard Dallas pathological criteria for the definition of myocarditis require that an inflammatory cellular infiltrate with or without associated myocyte necrosis be present on conventionally stained heart-tissue sections . These criteria are limited by variability in interpretation, lack of prognostic value, and low sensitivity, in part due to sampling error. These limitations have led to alternative pathological classifications with criteria that rely on cell-specific immunoperoxidase stains for surface antigens, such as anti-CD3, anti-CD4, anti-CD20, anti-CD68, and anti–human leukocyte antigen . Criteria that are based on immunoperoxidase staining have greater sensitivity and may have prognostic value.
Preliminary studies suggest that noninvasive cardiac magnetic resonance imaging (MRI) may provide an alternative method for diagnosis without the risks of biopsy. For example, regions of myocarditis are reported to correlate closely with regions of abnormal signal on cardiac MRI .
Recent recommendations : endomyocardial biopsy should be considered on the basis of the likelihood of finding specific treatable disorders.
Cooper L. N Engl J Med 2009;360:1526-1538
Clinical Scenarios for the Diagnosis of MyocarditisCooper L. N Engl J Med 2009;360:1526-1538
Contrast-Enhanced Magnetic Resonance Imaging (MRI) of the Heart of a 24-Year-Old Man with Acute Myocarditis. Cardiac MRI is being increasingly used to evaluate suspected acute myocarditis and to localize sites for endomyocardial biopsy, with additional detail shown with delayed gadolinium enhancement (Panel A, arrows), in a four-chamber view (Panel B, arrows), and in T2-weighted three-chamber views (Panels C and D, arrows). Scans provided courtesy of Dr. Jeannette Schultz- Menger.Figure 3. Contrast-Enhanced Magnetic Resonance Imaging (MRI) of the Heart of a 24-Year-Old Man with Acute Myocarditis. Cardiac MRI is being increasingly used to evaluate suspected acute myocarditis and to localize sites for endomyocardial biopsy, with additional detail shown with delayed gadolinium enhancement (Panel A, arrows), in a four-chamber view (Panel B, arrows), and in T2-weighted three-chamber views (Panels C and D, arrows). Scans provided courtesy of Dr. Jeannette Schultz-Menger.
Viral and postviral myocarditis remain major causes of acute and chronic dilated cardiomyopathy. Seroepidemiologic and molecular studies linked coxsackievirus B to outbreaks of myocarditis from the 1950s through the 1990s. The spectrum of viruses that were detected in endomyocardial biopsy samples shifted from coxsackievirus B to adenovirus in the late 1990s and, in the past 5 years, to parvovirus B19 and other viruses, according to reports from the United States and Germany.
Causative Agents
In Japan and in a serologic study of myocarditis in the United States, hepatitis C virus was also linked to myocarditis and dilated cardiomyopathy. Many other viruses have also been associated less frequently with myocarditis; these viruses include Epstein–Barr virus, cytomegalovirus, and human herpesvirus 6. The large number of observations that link viruses with myocarditis have led to ongoing treatment trials of antiviral therapy in patients with virus-associated cardiomyopathy.
certain other infectious causes of myocarditis should be considered in patients with acute or chronic cardiomyopathy. Borrelia burgdorferi (Lyme disease), Trypanosoma cruzi infection can present as acute myocarditis or chronic cardiomyopathy, Myocarditis is the most common cardiac pathological finding at autopsy of patients infected with the human immunodeficiency virus (HIV), with a prevalence of 50% or more. noninfectious disorders, such as cardiac sarcoidosis
Drug-induced hypersensitivity reactions and systemic hypereosinophilic syndromes can cause a specific myocarditis that often responds to withdrawal of the offending agent or to treatment of the underlying disorder, though adjuvant corticosteroid therapy is often required. anticonvulsants, antibiotics, and antipsychotics, have been implicated in hypersensitivity myocarditis.
Eosinophilic myocarditis is characterized by a predominantly eosinophilic infiltrate in the myocardium and may occur in association with systemic diseases, such as the hypereosinophilic syndrome, the Churg–Strauss syndrome, Lцffler's endomyocardial fibrosis, cancer, and parasitic, helminthic, or protozoal infections. Eosinophilic myocarditis has been reported after vaccination for several diseases, including smallpox.
Myocarditis may occur concomitantly with other cardiomyopathies and may have an adverse effect on the clinical course of the other condition. For example, the prognosis in cardiac amyloidosis is much worse if histologic evidence of myocarditis is present. Myocarditis has been associated with clinical deterioration in hypertrophic cardiomyopathy, and in such cases, evidence of a persistent viral genome may be identified in the myocardium.
Acute myocarditis is frequently first diagnosed as nonischemic dilated cardiomyopathy in a patient with symptoms that have been present for a few weeks to several months. However, manifestations range from subclinical disease to sudden death, with new-onset atrial or ventricular arrhythmias, complete heart block, or an acute myocardial infarction–like syndrome. Cardiac symptoms are variable and may include fatigue, decreased exercise tolerance, palpitations, precordial chest pain, and syncope. Chest pain in acute myocarditis can result from an associated pericarditis or, occasionally, from coronary-artery spasm.
a viral prodrome with fever, myalgia, and respiratory or gastrointestinal symptoms is classically associated with myocarditis. Most studies of acute myocarditis report a slight preponderance in male patients, An unusual cause of myocarditis, such as cardiac sarcoidosis, should be suspected in patients who present with chronic heart failure, dilated cardiomyopathy and new ventricular arrhythmias, or second-degree or third-degree heart block or who do not have a response to standard care.
Furthermore, myocarditis is an important cause of sudden death, as well as childhood cardiomyopathy. A recent long-term study of pediatric myocarditis demonstrated that the greatest burden of myocarditis may not be apparent for 6 to 12 years after diagnosis when children die or need to undergo cardiac transplantation for chronic dilated cardiomyopathy.
Most information about the molecular pathogenesis of viral and autoimmune myocarditis comes from rodent models. In these models, viruses appear to enter cardiac myocytes or macrophages through specific receptors and coreceptors.
The current understanding of the cellular and molecular pathogenesis of postviral and autoimmune myocarditis is based solely on animal models. In these models, the progression from acute injury to chronic dilated cardiomyopathy may be simplified into a three-stage process. Acute injury leads to cardiac damage, exposure of intracellular antigens such as cardiac myosin, and activation of the innate immune system.
Over weeks, specific immunity that is mediated by T lymphocytes and antibodies directed against pathogens and similar endogenous heart epitopes cause robust inflammation. In most patients, the pathogen is cleared and the immune reaction is down-regulated with few sequelae. However, in other patients, the virus is not cleared and causes persistent myocyte damage, and heart-specific inflammation may persist because of mistaken recognition of endogenous heart antigens as pathogenic entities.
CD4+ T lymphocytes are key mediators of cardiac damage in experimental autoimmune myocarditis. Autoantibodies to a variety of cardiac antigens are common in suspected or histologically confirmed lymphocytic myocarditis and dilated cardiomyopathy.
Streptococcal M protein and coxsackievirus B share epitopes with cardiac myosin, an intracellular antigen, and cross-reactive antibodies may result in the production of autoantibodies because of this antigenic mimicry. After viral clearance, cardiac myosin may provide an endogenous source of antigen in chronic myocarditis and stimulate chronic inflammation through autoimmune mechanisms. A series of studies during the past decade or so have described cross-reactivity between cardiac myosin and the endogenous human cell-surface protein laminin, suggesting that laminin could serve as an ongoing stimulus in chronic myocarditis. Recently, antibodies to cardiac myosin that cross-react with the β1-adrenergic receptor have been described, and these antibodies may contribute to cardiomyocyte apoptosis.
Biomarkers of cardiac injury are elevated in a minority of patients with acute myocarditis but may help confirm the diagnosis. Troponin I has high specificity (89%) but limited sensitivity (34%) in the diagnosis of myocarditis. Clinical and experimental data suggest that increased levels of cardiac troponin I are more common than increased levels of creatine kinase MB in acute myocarditis.
A few serologic and imaging biomarkers have been associated with poor clinical outcome. For example, relatively high serum levels of Fas ligand and interleukin-10 may predict an increased risk of death.
the electrocardiogram may show sinus tachycardia with nonspecific ST-segment and T-wave abnormalities. Occasionally, the changes on electrocardiography are suggestive of an acute myocardial infarction and may include ST-segment elevation, ST-segment depression, and pathologic Q waves. Pericarditis not infrequently accompanies myocarditis clinically and is often manifested in pericarditis-like changes seen on electrocardiography. The sensitivity of the electrocardiogram for myocarditis is low (47%). The presence of Q waves or left bundle-branch block is associated with higher rates of death or cardiac transplantation.
Echocardiography is useful primarily to rule out other causes of heart failure, since there are no specific features of acute myocarditis. Echocardiographic patterns of dilated, hypertrophic, restrictive, and ischemic cardiomyopathies have been described in histologically proven myocarditis. Segmental or global wall-motion abnormalities in myocarditis can simulate myocardial infarction. In the Myocarditis Treatment Trial, increased sphericity and left ventricular volume occurred in acute, active myocarditis. Fulminant myocarditis may be distinguished from acute myocarditis by a smaller left ventricular cavity size and increased wall thickness. The loss of right ventricular function was the most powerful predictor of death or the need for cardiac transplantation in a series of 23 patients with biopsy-confirmed myocarditis.
Cardiac MRI is being used with increasing frequency as a diagnostic test in suspected acute myocarditis and may be used to localize sites for endomyocardial biopsy. In a study by Mahrholdt et al., histopathological evaluation of biopsy specimens directed by contrast cardiac MRI with delayed enhancement demonstrated active myocarditis in 19 of 21 patients, although such evaluation without delayed enhancement showed active myocarditis in only 1 of 7 patients. A combination of T1-weighted and T2-weighted images had the best combination of sensitivity and specificity.
Endomyocardial biopsy should be performed in patients with unexplained, new-onset heart failure of less than 2 weeks' duration in association with a normal-size or dilated left ventricle and hemodynamic compromise, for suspected fulminant myocarditis. patients with unexplained, new-onset heart failure of 2 weeks' to 3 months' duration in association with a dilated left ventricle and new ventricular arrhythmias or Mobitz type II or second-degree or third-degree heart block . patients who do not have a response to usual care within 1 to 2 weeks, for suspected giant-cell myocarditis.
The mainstay of therapy for acute myocarditis is supportive therapy for left ventricular dysfunction. Most patients will improve with a standard heart-failure regimen that includes the administration of angiotensin-converting–enzyme inhibitors or angiotensin-receptor blockers, beta-blockers such as metoprolol and carvedilol, and diuretics.
In patients whose condition deteriorates despite optimal medical management, case series suggest a role for mechanical circulatory support, such as ventricular assist devices or extracorporeal membrane oxygenation, as a bridge to transplantation or recovery. The overall rate of survival after cardiac transplantation for myocarditis is similar to that for other causes of cardiac failure.
Since no clinical trials of therapy for heart failure have been conducted specifically in patients with myocarditis, the only relevant studies describe animal models. Patients recovering from acute myocarditis should refrain from aerobic activity for a period of months after the clinical onset of the disease, based on studies in rodents with myocarditis in which increased death rates were associated with sustained exercise. The reintroduction of aerobic activities somewhat depends on the severity of left ventricular dysfunction and the extent of recovery.
The use of candesartan improved survival in a murine model of viral myocarditis (60%, vs. 18% with no candesartan treatment). The use of carteolol, a nonselective beta-blocker, improved histopathological results and reduced wall thickness in coxsackievirus B myocarditis. The use of nonsteroidal antiinflammatory drugs was associated with increased mortality.
In patients with acute myocarditis, therapy for arrhythmias is also supportive, since such arrhythmias usually resolve after the acute phase of the disease, which can last several weeks. The 2006 guidelines of the American Heart Association, the American College of Cardiology, and the European Society of Cardiology recommend that arrhythmias be managed conventionally in patients with myocarditis. However, in acute myocarditis, temporary pacemakers may be required for patients with symptomatic bradycardia or complete heart block. Patients with symptomatic or sustained ventricular arrhythmias may need amiodarone and possibly an implantable cardioverter–defibrillator, even if active inflammation is still present.
The finding of viral genomes on endomyocardial biopsy has been used to guide treatment in acute and chronic cardiomyopathy. In some but not all studies, the presence of viral genomes was associated with subsequent worsening of heart function, the need for cardiac transplantation, and death. Data regarding the use of antiviral agents are currently limited to animal models and small case series. In murine viral myocarditis, antiviral therapy with ribavirin and interferon alfa reduced the severity of myocardial lesions and mortality. Antiviral therapy has been used in only one case series of fulminant myocarditis. Because most patients with acute myocarditis are diagnosed weeks after viral infection, it is unlikely that antiviral therapy would be provided early enough to be of benefit in acute viral myocarditis.
In contrast, interferon beta has been used successfully in patients with viral persistence in chronic, stable dilated cardiomyopathy. Viral clearance was achieved in all patients after antiviral treatment, with a significant increase in left ventricular function in the treatment group. Successful antiviral therapy or vaccines would need to be tailored to current viruses, since viruses that have been detected in the heart have changed from enterovirus in the 1980s to adenovirus in the 1990s and now to parvovirus B19 and human herpesvirus 6 — and because coinfections are common.
Antiviral and immunomodulatory effects that have been shown in experimental models and uncontrolled case series suggest that intravenous immune globulin (IVIG) might have a therapeutic use in myocarditis. However, in the Intervention in Myocarditis and Acute Cardiomyopathy trial, patients with acute dilated cardiomyopathy who were treated with IVIG did no better than those given placebo. Therefore, the routine use of IVIG for acute myocarditis in adults is not recommended. IVIG has not been evaluated rigorously for the treatment of chronic dilated cardiomyopathy with inflammation or viral persistence. IVIG may have a role in the treatment of acute pediatric myocarditis.
Results from several randomized, controlled trials of immunosuppression for acute myocarditis were negative or only marginally positive. These studies suggest that immunosuppression is not beneficial in the routine treatment of acute lymphocytic myocarditis.
There may be a broader role for immunosuppression in patients with chronic, moderate-to-severe cardiomyopathy, whose condition is unlikely to improve further after optimal care has been given for 6 to 12 months. In one trial involving 84 patients with chronic dilated cardiomyopathy and human leukocyte antigen expression on cardiomyocytes, the use of azathioprine and prednisone was associated with improvement in cardiac function and in New York Heart Association functional class.
The US Food and Drug Administration recommends that the coadministration of omeprazole and Plavix (clopidogrel) be avoided, based on new data showing that the proton pump inhibitor reduces the efficacy of Plavix by nearly 50%. Other drugs which inhibit the CYP2C19 drug- metabolising enzyme should also be avoided in combination with clopidogrel.
When compared with placebo or no antithrombotic treatment, warfarin reduces the risk of stroke by about two thirds in patients with atrial fibrillation, but this drug is underused because it is inconvenient and causes bleeding. Antiplatelet treatment with aspirin is much less effective than warfarin—it reduces the risk of stroke by about a fifth compared with placebo. Adding clopidogrel to aspirin improves the effectiveness of antiplatelet treatment to prevent stroke but the combination remains significantly less effective than warfarin.
Current guidelines recommend warfarin for patients with atrial fibrillation at high risk of stroke (previous stroke or embolism or more than one of the following risk factors: age ≥75 years, hypertension, diabetes, or congestive cardiac failure), either aspirin or warfarin for those at moderate risk (only one stroke risk factor), and aspirin for patients at low risk for stroke (no stroke risk factors).
October 8, 2010 — Abbott Laboratories has withdrawn the obesity drug sibutramine (Meridia) from the market in light of clinical trial data pointing to an increased risk for stroke and myocardial infarction, the US Food and Drug Administration (FDA) announced today. Medscape 10/08/2010
The agency asked Abbott Laboratories to pull the drug from the market after it evaluated data from a postmarketing study of the drug's cardiovascular safety. The study, called the Sibutramine Cardiovascular Outcomes Trial (SCOUT), demonstrated a 16% increase in the risk for serious cardiovascular events such as nonfatal heart attack, nonfatal stroke, the need for resuscitation after the heart stopped, and death in a cohort of patients given sibutramine compared with another given a placebo.
In industrialized countries, sudden cardiac death (SCD) is a major cause of mortality. Although the precise incidence remains unknown, in the United States alone the estimated occurrence of SCD is approximately 300,000 deaths annually. Furthermore, 50% of all heart-related deaths are attributed to SCD. Sudden cardiac arrest (SCA) precedes SCD and often leads to SCD in many but not all incidences. Studies of patients suffering SCA and of patient autopsies have revealed that tachyarrhythmia is the leading cause of SCD. Additionally, patients with heart failure and reduced left ventricular ejection fraction are also at high risk.
Wearable Defibrillators as a Bridge to ICD Implantation
Medscape 07/08/2010
Recent studies have demonstrated the benefits of implantable cardioverter-defibrillator (ICD) therapy in improving survival in patients with a previous episode of SCD, left ventricular dysfunction, and/or ventricular tachyarrhythmias. However, high occurrences of SCD in populations who were not eligible to receive an ICD for up to 4 months suggests that these populations are at higher risk than expected, necessitating more widespread application of an alternate defibrillator device.
Although many patients who do not meet indications for ICD implantation are still at substantial high risk for SCD, several approaches have been utilized for primary prevention. One primary prevention approach includes an automatic external defibrillation device in the home and workplace. When accomplished by nonmedical personnel, this approach was shown to be successful for improving survival after cardiac arrest due to tachyarrhythmia. However, this approach requires that the time period between arrest and resuscitation be short and that the cardiac arrest must be witnessed.
The introduction of the wearable cardioverter-defibrillator, which detects and treats ventricular tachyarrhythmia, eliminates the need for a second individual to administer therapy. Recent data demonstrated that the device is beneficial in detecting and effectively treating ventricular tachyarrhythmia in high-risk patients who are unclear candidates for ICD therapy.
In analyses adjusted for age, sex, comorbidity, and concomitant medical therapies, risk for fatal or serious nonfatal bleeding was 3.7-fold higher in patients who received triple therapy (warfarin plus aspirin plus clopidogrel) versus warfarin alone, 3.1-fold higher in patients who received warfarin plus clopidogrel, and 1.7- to 1.8-fold higher in patients who received aspirin plus clopidogrel or aspirin plus warfarin. No benefit was noted for triple therapy or warfarin plus clopidogrel in lowering risk for ischemic stroke.
Comment: These results show that adding platelet inhibition to warfarin — a common practice — significantly raised risk for fatal and serious bleeding. Warfarin plus clopidogrel and triple therapy are particularly risky combinations. These data argue for much greater care in the use of platelet inhibition with warfarin even when a strong indication exists to use both. For example, in a patient with a mechanical prosthetic valve or AF with high risk for stroke who requires antiplatelet therapy for stenting, bare-metal (rather than drug-eluting) stents should be considered preferentially to shorten the length of time that the patient receives triple therapy. Journal Watch General Medicine October 7, 2010
Acute right ventricular MI In patients presenting with acute right ventricular MI, abnormalities in the standard 12 lead ECG are restricted to ST elevation greater than or equal to 1 mm in lead aVR. Although isolated right ventricular MI is usually seen in patients suffering from chronic lung disease together with right ventricular hypertrophy, it can occur in patients suffering a transmural infarction of the inferior-posterior wall which extends to involve the right ventricular wall as well. Right ventricular MI is most commonly caused by obstruction of the proximal right coronary artery and is frequently associated with right bundle branch block. Furthermore, only 5% - 10% of patients suffer from hemodynamic symptoms.
According to conventional wisdom, ventricular tachychardia or fibrillation (VT/VF) in the first 48 hours after an ST-segment-elevation MI signifies poor short- and long-term prognoses, and VT/VF occurring >48 hours after MI indicates increased arrhythmic risk. However, these suppositions are derived largely from thrombolytic trials.
To find out whether they still hold true now that MI is usually treated with percutaneous coronary intervention, investigators conducted a post hoc analysis of data from the APEX AMI trial of pexelizumab versus placebo in 5745 PCI-treated STEMI patients.
VT/VF occurred in 329 patients (5.7%); 90% of these events occurred within 48 hours after MI. Patients who experienced VT/VF had worse prognostic indicators than those who did not, both at baseline (e.g., preprocedure TIMI flow of 0, higher mean Killip class) and after PCI (e.g., postprocedure TIMI flow of <3, ST resolution of <70%). In multivariate analysis, 90-day mortality increased twofold when VT/VF occurred before the end of cardiac catheterization and increased fivefold when VT/VF occurred after the procedure. Most deaths in patients with VT/VF were cardiac (90%), with sudden cardiac death accounting for 40%.
Comment: PCI does not appear to improve the prognosis of patients who experience ventricular tachycardia or fibrillation with STEMI. The poor prognosis is largely driven by the severity of illness: VT/VF tends to occur in patients with larger MIs and poorer PCI outcomes. This was a retrospective analysis of data from a trial that did not address whether treatment of VT/VF in this patient population would improve outcomes. In clinical practice, an implantable cardioverter-defibrillator is generally offered to individuals in whom VT/VF occurs at least 48 hours after MI onset.
JAMA 2009 May
A variety of definitions has been used to signify the duration and rate of arrhythmia qualifying as nonsustained VT. Currently, the most commonly used is three or more consecutive ventricular premature depolarizations, up to a maximum duration of 30 seconds before spontaneous termination.