Drug treatment of systolic and of diastolic heart failure in elderly persons

Underlying causes, risk factors, and precipitating causes of heart failure (HF) should be treated. Patients with HF and an abnormal left ventricular ejection fraction (systolic HF) or normal left ventricular ejection fraction (diastolic HF) should be treated with diuretics if fluid retention is present, with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker if the patient cannot tolerate an ACE inhibitor because of cough, angioneurotic edema, rash, or altered taste sensation, and with a beta blocker unless contraindicated. If severe systolic HF persists, an aldosterone antagonist should be added. If HF persists, isosorbide dinitrate plus hydralazine should be added. Calcium channel blockers should be avoided if systolic HF is present. Digoxin should be avoided in men and women with diastolic HF if sinus rhythm is present and in women with systolic HF. Digoxin should be given to men with systolic HF if symptoms persist, but the serum digoxin level should be maintained between 0.5 and 0.8 ng/ml. Cardiac synchronized pacing should be considered in patients with severe systolic HF despite optimal medical therapy, with sinus rhythm, and with ventricular dyssynchrony.     

Epidemiology,pathophysiology, prognosis,and treatment of systolic and diastolic heart failure in elderly patients

American College of Cardiology/American Heart Association class I recommendations for treating patients with heart failure (HF) and abnormal left ventricular ejection fraction are diuretics in patients with fluid retention, an angiotensin-converting enzyme (ACE) inhibitor unless contraindicated, a beta-blocker unless contraindicated, digoxin for the treatment of symptoms of HF, and withdrawal of drugs known to precipitate or aggravate HF such as nonsteroidal anti-inflammatory drugs, calcium channel blockers, and most antiarrhythmic drugs. Class II(a) recommendations for treating HF with abnormal left ventricular ejection fraction are spironolactone in patients with class IV symptoms, preserved renal function, and normal serum potassium; exercise training as an adjunctive approach to improve clinical status in ambulatory patients; an angiotensin receptor blocker in patients who cannot be given an ACE inhibitor because of cough, rash, altered taste sensation, or angioedema; and hydralazine plus nitrates in patients being treated with diuretics, a beta-blocker, and digoxin who cannot be given an ACE inhibitor or an angiotensin receptor blocker because of hypotension or renal insufficiency. Patients with diastolic HF should be treated with cautious use of diuretics and with a beta-blocker. An ACE inhibitor should be added if HF persists or an angiotensin receptor blocker if the patient cannot tolerate an ACE inhibitor because of cough, angioedema, rash, or altered taste sensation. Isosorbide dinitrate plus hydralazine should be added if HF persists. A calcium channel blocker should be added if HF persists. Digoxin should be avoided in diastolic HF if sinus rhythm is present.     

Heart failure update 2010 and current ESC guidelines

Chronic heart failure may be caused by systolic pump failure and/or impairment of diastolic filling of the ventricles. Standard pharmacotherapy of systolic heart failure includes an ACE inhibitor, betablocker, diuretics and in patients with severe symptoms a low-dose aldosterone antagonist. An AT(1) receptor blocker is indicated in those not tolerating ACE inhibitors. If patients remain in functional class NYHA III-IV despite optimal medication and have cardiac dyssynchrony, biventricular pacing may improve symptoms and prognosis. While evidence-based treatment significantly reduces morbidity and mortality in systolic heart failure, hardly any results of clinical trials are available for diastolic heart failure. Therefore, therapy in patients with diastolic heart failure remains symptomatic in most cases.     

Diastolic dysfunction and heart failure with preserved ejection fraction: rationale for RAAS antagonist/CCB combination therapy

A large number of patients who present with signs or symptoms of heart failure (HF) do not have evidence of left ventricular systolic dysfunction. As a result, HF in the presence of normal or preserved ejection fraction, or diastolic HF, is increasingly recognized as a health care challenge. Guidelines have been issued for the classification, diagnosis, and prevention of HF from diastolic dysfunction, but treatment of this condition remains problematic. Antihypertensive agents that have been proven in clinical trials to improve outcomes in HF with systolic dysfunction, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and β-blockers, have not yet demonstrated comparable benefits in patients with diastolic dysfunction. Combination therapy using an antagonist of the renin-angiotensin-aldosterone system and a calcium-channel blocker has potential advantages over monotherapy and is being explored in several ongoing clinical trials.     

Leitliniengerechte Therapie der chronischen Herzinsuffizienz

Chronic heart failure may be caused by systolic pump failure and/or impairment of diastolic filling of the ventricles. The standard pharmacotherapy for systolic heart failure includes an ACE inhibitor, betablocker, diuretics and, in patients with severe symptoms, a low dose aldosterone antagonist. An AT1 receptor blocker is indicated for those patients who do not tolerate ACE inhibitors. If patients remain in the functional class NYHA III-IV despite optimal medication and have cardiac dyssynchrony, biventricular pacing may improve the symptoms and prognosis. While evidence-based treatment significantly reduces morbidity and mortality in systolic heart failure, hardly any results from clinical trials are available for diastolic heart failure. Therefore, therapy in patients with diastolic heart failure remains in most cases empirical.     

Herzinsuffizienz Update 2010 und aktuelle ESC-Leitlinien

Chronic heart failure may be caused by systolic pump failure and/or impairment of diastolic filling of the ventricles. Standard pharmacotherapy of systolic heart failure includes an ACE inhibitor, betablocker, diuretics and in patients with severe symptoms a low-dose aldosterone antagonist. An AT₁ receptor blocker is indicated in those not tolerating ACE inhibitors. If patients remain in functional class NYHA III-IV despite optimal medication and have cardiac dyssynchrony, biventricular pacing may improve symptoms and prognosis. While evidence-based treatment significantly reduces morbidity and mortality in systolic heart failure, hardly any results of clinical trials are available for diastolic heart failure. Therefore, therapy in patients with diastolic heart failure remains symptomatic in most cases.     

Heart failure update: treatment of heart failure with a normal left ventricular ejection fraction in the elderly

Heart failure (HF) affects approximately 5 million persons in the United States; more than 550,000 new cases of HF are reported each year. Prevalence of HF with a normal left ejection fraction increases with age and is higher in older women than older men. Both underlying and precipitating causes of HF should be treated when possible. Hypertension, especially isolated systolic hypertension, should be treated with diuretics, ACE inhibitors, and beta blockers. Myocardial ischemia should be treated with nitrates and beta blockers. Anemia should be treated, as should hyperthyroidism, hypothyroidism, and obstructive sleep apnea. Use of inappropriate drugs, such as nonsteroidal anti-inflammatory drugs, should be avoided. Coronary revascularization should be performed in selected individuals.     

Managing the hypertensive patient with ischemic heart disease

Thiazide diuretics, b-blockers, calcium channel blockers, and angiotensin converting enzyme (ACE) inhibitors are all superior to placebo for the primary prevention of coronary events in patients with hypertension. Recent studies have shown that ACE inhibitors are better than other antihypertensive agents in lowering overall cardiovascular morbidity and mortality, especially stroke. Blood pressure should be aggressively lowered (to < 140/90 mm Hg), especially in diabetic patients (to < 130/80 mm Hg), but care should be exercised in lowering the diastolic blood pressure below 65 mm Hg in patients with significant occlusive coronary artery disease. Hypertension in patients with stable angina should be treated with a b-blocker (alternatively a calcium channel blocker) together with an ACE inhibitor. Patients with hypertension and acute coronary syndrome (unstable angina or myocardial infarction) should be treated with a b-blocker, and with an ACE inhibitor if there is left ventricular dysfunction. A thiazide diuretic and/or a dihydropyridine calcium channel blocker could be added for blood pressure control. Calcium channel blockers should be avoided if there is significant left ventricular dysfunction.     

Beta-blockers, angiotensin-converting enzyme inhibitors, and calcium antagonists in treatment of elderly patients with acute myocardial infarction

Administration of beta-blockers reduces mortality among old persons during and after acute myocardial infarction. The American College of Cardiology/American Heart Association guidelines recommend that persons without contraindications to use of beta-blockers should be administered beta-blockers within a few days of myocardial infarction (if administration is not initiated acutely) and that their administration should be continued indefinitely. These guidelines also recommend the use of angiotensin converting enzyme inhibitors in treating persons within the first 24 h of suspected onset of acute myocardial infarction with ST-segment elevation in two or more anterior precordial leads or with congestive heart failure in the absence of significant hypotension or other contraindications to use of ACE inhibitors; and persons during and after convalescence from acute myocardial infarction with congestive heart failure associated with an abnormal left ventricular ejection fraction (LVEF) or with asymptomatic left ventricular systolic dysfunction with a LVEF < 40%. These guidelines state that there are no class I indications for using calcium antagonists after myocardial infarction. If patients have persistent angina pectoris after myocardial infarction despite treatment with beta-blockers and nitrates or hypertension inadequately controlled by other drugs, administration of a nondihydropyridine calcium antagonist such as verapamil or diltiazem should be added to the therapeutic regimen if the LVEF is normal. If the LVEF is abnormal, administration of amlodipine or felodipine should be added to the therapeutic regimen.     

Left atrial volume, geometry, and function in systolic and diastolic heart failure of persons > or =65 years of age (the cardiovascular health study)

The left atrium enlarges in association with many factors, including aging, atrial fibrillation, hypertension, diastolic dysfunction, and heart failure (HF) with low ejection fraction. However, left atrial (LA) volume, geometry, and emptying have not been compared between diastolic and systolic HF, nor has the association of LA volume for new HF been determined in older subjects, many of whom have normal ejection fraction. We used echocardiography to measure the LA volume, geometry, and emptying in 851 community-dwelling subjects > or =65 years of age, including 180 with HF at baseline and 255 participants who subsequently developed HF. The LA volume, area, and linear dimensions were higher in the prevalent and incident HF groups than in controls and did not differ between those with systolic versus diastolic HF, independent of co-morbidities and Doppler measures of diastolic function. The fractional area change was associated with prevalent, but not incident, HF. In conclusion, in population-based older subjects, the LA size is increased and LA emptying decreased in patients with either systolic or diastolic HF. LA size is associated with the new development of HF. These findings highlight the important role of the left atrium in HF, with or without a decreased ejection fraction.     

Contribution of left ventricular diastolic dysfunction to heart failure regardless of ejection fraction

Heart failure (HF) has been classified as systolic and diastolic based on the left ventricular ejection fraction. We hypothesized that left ventricular diastolic dysfunction is an important element of HF regardless of ejection fraction. Two hundred six patients who had clinical HF were compared with 72 age-matched controls. Diastolic dysfunction, as assessed by the mitral filling pattern and tissue Doppler imaging, was present in >90% of patients who had HF regardless of ejection fraction and was more frequent and severe than in age-matched controls (p <0.001). In patients who had HF, B-type natriuretic peptide correlated with diastolic dysfunction (r = 0.62, p <0.001) but not with ejection fraction or end-diastolic volume index (EDVI). The degree of diastolic dysfunction influenced survival rate (risk ratio 1.64, p <0.05), whereas ejection fraction and EDVI did not. Systolic function measured by systolic mitral annular velocity was decreased in patients who had HF and an ejection fraction /=0.50 (6.6 +/- 1.8 cm/s) compared with control subjects (8.0 +/- 2.1 cm/s, p <0.01). Patients who had HF and an ejection fraction >/=0.50 had an increased ratio of ventricular mass to EDVI. Patients who had HF and an ejection fraction /=0.50 is associated with mild systolic dysfunction and an increased ratio of left ventricular mass to EDVI. In HF with an ejection fraction 相似文献   

A statin in the treatment of heart failure? Controlled rosuvastatin multinational study in heart failure (CORONA): Study design and baseline characteristics

BACKGROUND: Previous prospective outcome studies of statins have not provided any guidance on benefit-risk in patients with heart failure. AIM: The primary objective is to determine whether rosuvastatin (10 mg) reduces the combined endpoint of cardiovascular mortality, non-fatal myocardial infarction or non-fatal stroke (time to first event). The first secondary endpoint is all-cause mortality. METHODS: CORONA is a randomized, double-blind, placebo-controlled trial. Briefly, men and women, aged > or =60 years with chronic symptomatic systolic heart failure of ischemic aetiology and ejection fraction < or =0.40 (NYHA class III and IV) or < or =0.35 (NYHA class II) were eligible if they were not using or in need of cholesterol lowering drugs. RESULTS: Mean age was 73 years (n=5016; 24% women), with 37% in NYHA II and 62% in NYHA III, ejection fraction 0.31, total cholesterol 5.2 mmol/L. Sixty percent have a history of myocardial infarction, 63% hypertension, and 30% diabetes. Patients are well treated for heart failure with 90% on loop or thiazide diuretics, 42% aldosterone antagonists, 91% ACE inhibitor or AT-I blocker, 75% beta-blockers, and 32% digitalis. CONCLUSION: CORONA is important for three main reasons: (1) A positive result is very important because of the high risk of the population studied, the increasing prevalence of elderly patients with chronic symptomatic systolic heart failure in our society, and the health economic issues involved. (2) If negative, new mechanistic questions about heart failure have to be raised. (3) If neutral we can avoid unnecessary polypharmacy.     

Left Ventricular Diastolic Dysfunction in End‐Stage Kidney Disease: Pathogenesis,Diagnosis, and Treatment

Diastolic dysfunction is frequently observed in end‐stage kidney disease (ESKD), and ESKD patients have many risk factors for heart failure (HF), including hypertension, diabetes, and coronary artery disease. Diastolic HF, also called HF with preserved ejection fraction, refers to a clinical syndrome in which patients have symptoms and signs of HF, normal or near normal left ventricular (LV) systolic function, and evidence of diastolic dysfunction manifested by abnormal LV filling and elevated filling pressure. Recent reports suggest that HF with preserved ejection fraction is more common in hemodialysis patients than HF with low ejection fraction. Diastolic HF in ESKD patients is a strong predictor of death. In this article, we review the information available in the literature on the pathogenesis, diagnosis, and potential treatment strategies of diastolic dysfunction or diastolic HF based on evidence obtained in the general population that is potentially applicable to ESKD patients.     

Efficacy of eplerenone added to renin-angiotensin blockade in hypertensive patients

The efficacy and tolerability of eplerenone, a selective aldosterone blocker, was assessed when added to existing antihypertensive therapy with an ACE inhibitor or an angiotensin II receptor blocker (ARB). Hypertensive patients (n=341) whose blood pressure (BP) was not controlled despite ACE inhibitor or ARB were randomized (double-blind) to receive 50 mg eplerenone (increasing to 100 mg if required) once daily or placebo for 8 weeks. Diastolic and systolic BP and adverse events were recorded. By study end (week 8), mean seated diastolic BP was significantly reduced from week 0 among patients receiving eplerenone/ARB (-12.7+/-0.81 mm Hg) compared with those receiving placebo/ARB (-9.3+/-0.83 mm Hg). The change in mean seated diastolic BP was -9.9+/-0.88 mm Hg in eplerenone/ACE inhibitor patients and -8.0+/-0.86 mm Hg in placebo/ACE inhibitor patients (P=NS). Systolic BP levels were also significantly lower at week 8 for eplerenone/ACE inhibitor (-13.4+/-1.35 mm Hg) and eplerenone/ARB (-16.0+/-1.37 mm Hg) patients, respectively, compared with placebo/ACE inhibitor (-7.5+/-1.31 mm Hg) and placebo/ARB patients (-9.2+/-1.41 mm Hg). Adverse events were generally nonsevere and not significantly different between eplerenone and placebo. This study demonstrated that in patients whose BP was not controlled with an ACE inhibitor or ARB, the addition of eplerenone over an 8-week period significantly lowered systolic BP in both groups and diastolic BP in ARB patients. Selective aldosterone blockade with eplerenone, therefore, may be useful add-on therapy in hypertensive patients inadequately controlled on ACE inhibitor or ARB alone.     

Digoxin

After 200 years of use, digitalis still appears to have a place in our armamentarium for heart failure and atrial fibrillation despite the proven survival benefits with ACE inhibitors and beta-blockers. Digoxin therapy is inexpensive and well tolerated and may result in considerable savings. Digoxin is the only oral inotrope that does not increase mortality in heart failure patients, particularly if low doses are being used. Digoxin therapy should be used in patients with systolic heart failure who continue to have signs and symptoms despite therapeutic doses of ACE inhibitors or diuretics or in patients with atrial fibrillation with or without heart failure for rate control.     

Diastolic heart failure demystified

The mystery of diastolic heart failure (DHF), described by authorities as a "puzzle" and a "clinical paradox," stems from the following misperception: (1) that the normal ejection fraction implies normal cardiac output (CO), (2) that therefore low CO is not operative (it is rarely mentioned in relation to the pathophysiology of DHF), and (3) the congestive phenomena are due to the stiff left ventricle. In fact, a normal ejection fraction is not a reliable indicator of normal CO; low CO is the fundamental pathophysiologic abnormality of all heart failure (HF), whether systolic and/or diastolic (or, indeed, "high output"); and increased ventricular stiffness is not the principal cause of congestion in DHF. Pathophysiologic explorations supporting these understandings further reveal the following: (1) the premise that a clinical event as dramatic as acute pulmonary edema (systolic and/or diastolic) would be contingent on similarly dramatic acute hypertensive or ischemic ventricular dysfunction, while intuitive, is unsubstantiated, and there is an alternate explanation satisfying both theoretical and clinical observations; (2) contrary to general perception, DHF is no more vulnerable to diuretic-induced hypotension than systolic HF; (3) heart rate reduction should not yet be considered an established therapeutic goal in DHF; (4) since HF is HF whether systolic and/or diastolic, studies are likely to show that therapeutic similarities outweigh differences except as the various agents might modify the underlying structural and/or functional pathology; (5) although long evident that HF occurs by only two mechanisms (systolic dysfunction and/or diastolic dysfunction), it has only recently been acknowledged that the mere exclusion of one is diagnostic of the other; and (6) the definition of HF currently in widespread use is unnecessarily confounded by neglect of the fundamental distinction between ventricular dysfunction and failure.     

Diabetic cardiomyopathy and diastolic heart failure - Difficulties with relaxation

Diabetic patients carry a four- to five-fold increased risk of heart failure. Hyperglycaemia plays a central role in the pathogenesis of diabetic cardiomyopathy. Diabetic cardiomyopathy represents a distinct structural and functional disorder of the myocardium characterized by cardiac hypertrophy and an increased myocardial stiffness. At an early stage, diabetic cardiomyopathy is manifested by diastolic heart failure with preserved ejection fraction. In some patients, diastolic dysfunction may progress to heart failure with reduced ejection fraction and result in overt systolic heart failure. Diastolic dysfunction can accurately be diagnosed by echocardiography and BNP measurement in daily clinical practice. Early treatment is prognostically important. Optimal control of blood glucose levels and blood pressure is beneficial. So far metformin is the only antidiabetic agent not associated with harm in diabetic patients with heart failure. Incretin-based therapies potentially provide cardiovascular benefits. ACE inhibitors, angiotensin-1 receptor antagonists and beta-blockers should be preferred in heart failure therapy.     

An update on diastolic dysfunction

Diastolic dysfunction refers to abnormal diastolic filling properties of the left ventricle regardless of whether systolic function is normal or the patient has symptoms. Diastolic heart failure (HF), or more accurately, HF with preserved systolic function, is a distinct clinical entity characterized by the presence of the triad of impaired diastolic function, normal systolic function (left ventricular ejection fraction > 50%), and symptoms of HF. Patients with HF with preserved systolic function are frequently symptomatic from both acute and chronic elevations in left ventricular end-diastolic pressure and/or left atrial pressure.     

Diastolic dysfunction and diastolic heart failure: Mechanisms and epidemiology

Studies have demonstrated that diastolic dysfunction is frequently present in asymptomatic community-based individuals, especially in the elderly with hypertension, coronary artery disease, and diabetes. The presence of diastolic dysfunction is a predictor for the development of heart failure (HF) and confers a higher risk of mortality. These findings have raised the question of whether treating preclinical diastolic dysfunction will be helpful in preventing or delaying the onset of clinical HF and mortality, as has been proven with treatment of asymptomatic left ventricular systolic dysfunction. In addition, in some individuals, diastolic dysfunction in the presence of a normal ejection fraction is associated with exercise intolerance as well as symptomatic clinical HF, referred to as diastolic HF. Patients with diastolic HF, who are more often elderly women, have a significant mortality and morbidity burden compared with agematched controls. Studies that further our understanding of mechanisms underlying diastolic dysfunction and diastolic HF will provide potential new targets for development of effective therapies for these conditions.