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.     

Usefulness of tissue Doppler imaging for estimation of left ventricular filling pressures in patients with systolic and diastolic heart failure

The diagnostic usefulness of the mitral E/E' ratio (derived from tissue Doppler imaging) as an estimate of left ventricular filling pressures was studied in 28 patients with diastolic heart failure (defined by heart failure signs and symptoms but with preserved ejection fraction) and in 46 patients with systolic heart failure (heart failure signs and symptoms and reduced ejection fraction). E/E' was reflective of filling pressures in subjects with diastolic and systolic heart failure and may be of special use in ruling out elevated filling pressures in subjects with suspected diastolic heart failure.     

Dyspnoe bei normaler systolischer Funktion

30-50% of patients presenting with symptoms of congestive heart failure exhibit a near normal left ventricular systolic function at rest, and an impaired diastolic function of the heart may be causative. Despite a better prognosis than in systolic heart failure, frequency of hospitalizations due to diastolic heart failure is comparable with systolic heart failure. According to the criteria of Vasan and Levy diagnosis of diastolic heart failure is probable, if symptoms and signs of heart failure are accompanied in proximity (within 72 h) by objective evidence of normal left ventricular systolic function. Newer echocardiographic techniques (e. g., tissue Doppler) aid to confirm the diagnosis and to determine the severity of dysfunction and may substitute invasive demonstration of impaired left ventricular relaxation, filling, compliance or stiffness for standardized diagnosis. Incorporation of biochemical test (BNP [brain natriuretic peptide]) allows differential diagnosis and may increase the accuracy of diagnosis. Due to inconsistent diagnostic criteria, data from prospective randomized controlled trials for the treatment of diastolic heart failure are rare. Basic principles include treatment of the underlying disease, i. e., control of hypertension, diabetes, or obstructive airway disease. Angiotensin 1 antagonists (ARB) have proven effective in regression of left ventricular hypertrophy (LIFE) and may reduce morbidity, but not mortality (CHARM). Maintenance of sinus rhythm, heart rate control (beta-blockers, calcium channel blockers) and anti-ischemic therapy may be indicated in view of pathophysiological aspects. Diuretics should be administered with caution in patients with symptoms of congestion, digitalis is not useful in the treatment of isolated diastolic heart failure. The results of ongoing trials (e. g., I-Preserve) may offer new therapeutic options, and evidence-based guidelines for the so far often unsatisfactory treatment of diastolic dysfunction/heart failure are awaited.     

Diastolic heart failure. Paroxysmal or chronic?

Heart failure with preserved systolic function is considered by some to be synonymous with diastolic heart failure (DHF). Although recent epidemiological studies have suggested that DHF constitutes 30–50% of all patients with heart failure, many cardiologists dealing with ambulant heart failure patients on a daily basis find that the vast majority of heart failure patients have systolic dysfunction. What could be the reasons for this? Referral bias and varying diagnostic thresholds and interpretation of results could be one important reason. Heart failure with preserved systolic function comprises a heterogeneous group of conditions: whilst some patients may truly have DHF, others may have heart failure due to subtle systolic dysfunction (noted on tissue Doppler imaging of the left ventricular long axis). Other patients actually have pulmonary disease, obesity or ischaemic heart disease, and have their symptoms attributed to ‘diastolic heart failure’ on the basis of ‘abnormal’ mitral diastolic flow indices that may, in fact, simply reflect aging. True DHF may be much less prevalent than suggested. A further possibility is that heart failure in patients with diastolic dysfunction might be paroxysmal rather than chronic. This group of patients may present predominantly to acute units like accident and emergency, coronary care units and intensive care units and are, therefore unlikely to figure prominently in the usual outpatient population of chronic systolic left ventricular dysfunction.     

Aspects of the Use of Angiotensin-Converting Enzyme Inhibitors and Calcium Antagonists in Treatment of Heart Failure in the Older Patient

The syndrome of congestive heart failure may result from either systolic or diastolic dysfunction of the left ventricle. Diastolic left ventricle dysfunction is particularly common in the geriatric age group, and is associated with left ventricular hypertrophy resulting from aging and hypertension. The clinical differentiation of these two patterns is important in understanding the pathophysiologic process and in selecting appropriate therapy. Angiotensin-converting enzyme (ACE) inhibitors are useful in systolic dysfunction, both in improving clinical manifestations of reduced cardiac output and in actually prolonging survival. ACE inhibitors are also beneficial in diastolic heart failure by promoting regression of left ventricular hypertrophy, thus improving diastolic physiological function. Calcium antagonists improve diastolic function by reducing blood pressure of hypertensive subjects, reducing left ventricular mass, and theoretically, by facilitating the energy-dependent transport of calcium ions from the actin-myosin complex into the sarcoplasmic reticulum. However, because of the negative inotropic properties of the calcium antagonists, they should be used cautiously, if used at all, in patients with significant systolic dysfunction, at least until the results of clinical trials using these drugs in systolic congestive heart failure are available.     

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.     

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.     

Effects of enalapril on heart failure in hypertensive patients with diastolic dysfunction.

Ten hypertensive patients with symptoms of heart failure and normal systolic function but with diastolic dysfunction were treated with 10 mg enalapril twice a day for 9 +/- 3 months to evaluate the effects of this agent alone on heart failure induced by diastolic dysfunction. After therapy, all patients improved and echocardiographic parameters of diastolic dysfunction became normalized. It is concluded that enalapril appears to be useful in the treatment of heart failure in hypertensive patients with normal systolic function and diastolic dysfunction.     

Therapy for diastolic heart failure

There is little objective to guide the therapy of patients with diastolic heart failure. Because of the similarities of pathophysiology abnormalities in diastolic and systolic heart failure, it is a reasonable inference to suggest that the proven therapy for systolic heart failure may also be of benefit in patients with diastolic heart failure. Treatment of underlying or exacerbating conditions in diastolic heart failure, such as hypertension, left ventricular hypertrophy, ischemia, diabetes, anemia, obesity and pulmonary disease is an important means of managing diastolic heart failure. Control of systolic blood pressure is effective in improving and preventing the development of diastolic heart failure. Treatment of diastolic heart failure is most effective when it is associated with hypertension. Production of systolic arterial pressure acutely reduces pulmonary congestion, ischemia, and chronically may lead to regression of left ventricular hypertrophy. Patients with diastolic heart failure in the absence of hypertension are very difficult to treat.     

Left ventricular diastolic dysfunction as a cause of congestive heart failure. Mechanisms and management.

OBJECTIVE: To define the mechanisms underlying left ventricular diastolic dysfunction in patients with congestive heart failure and normal systolic function and to identify the patients at risk for this syndrome. STUDY SELECTION: Studies were selected that describe the clinical observations of congestive heart failure with normal systolic function and that provide experimental and clinical insights into the mechanisms responsible for ventricular diastolic dysfunction. DATA SYNTHESIS: Recent studies indicate that a large number of patients (up to 40% in some series) presenting with congestive heart failure have preserved left ventricular systolic function. The factors contributing to altered left ventricular diastolic function include fibrosis, hypertrophy, ischemia, and increased afterload. The latter three factors, alone or in combination, predispose to impaired left ventricular relaxation, an active energy-requiring process. Thus, decreased left ventricular diastolic distensibility (increased diastolic pressure at any level of diastolic volume) may arise not only from altered passive elastic properties stemming from fibrosis or increased muscle mass but also from derangements in the dynamics of ventricular relaxation. RESULTS: In patients with essential hypertension, all four of the above mechanisms may be operative. Considering the prevalence of hypertension in the general population, hypertension appears to be an important underlying factor in many patients with heart failure on the basis of diastolic mechanisms. In the patient presenting with dyspnea and elevated filling pressures, but with a nondilated, normally contracting ventricle, treatment with standard heart failure medications (such as digitalis, diuretics, and vasodilators) is often ineffective and may be deleterious. Such patients may respond more favorably to beta-blockers and calcium-channel blockers. CONCLUSIONS: Diastolic dysfunction should be considered in the patient presenting with heart failure symptoms but with normal systolic function, particularly in hypertensive patients with left ventricular hypertrophy.     

Epidemiology, pathophysiology, prognosis, and treatment of systolic and diastolic heart failure

Underlying causes, risk factors, and precipitating causes of heart failure (HF) should be treated. Drugs known to precipitate or aggravate HF such as nonsteroidal antiinflammatory drugs should be stopped. Patients with HF and a low left ventricular ejection fraction (systolic heart failure) or normal 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.     

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.     

Angiotensin II receptor blockers in the treatment of heart failure

Heart failure treatment centers on antagonism of the renin-angiotensin-aldosterone system and adrenergic nervous system. Angiotensin-converting enzyme (ACE) inhibitors have been shown to benefit patients with left ventricular systolic dysfunction irrespective of symptoms. Despite ACE inhibitor use, left ventricular dysfunction continues to progress in most patients. In addition, ACE inhibitors are substantially underused in patients who would benefit, in large part due to physician concern over potential adverse effects. Angiotensin receptor blockers (ARBs) have been proposed as either potential substitutes for ACE inhibitors or as additive therapy for heart failure patients. The authors will review the importance of the renin-angiotensin-aldosterone system in the progression of heart failure, as well as the mechanisms by which ACE inhibitors and ARBs counteract this effect. The clinical evidence to date supporting the use of ARBs in heart failure also will be reviewed. Based on current trials, ARBs are suitable substitutes for ACE inhibitors in patients who have true ACE inhibitor intolerance, but ACE inhibitors should still be considered first-line therapy in the treatment of left ventricular systolic dysfunction and heart failure. ARBs are a reasonable additive therapy in patients on maximal ACE inhibitor therapy who remain symptomatic, especially in patients unable to tolerate beta blockade.     

Comparison of frequencies of left ventricular systolic and diastolic heart failure in Chinese living in Hong Kong.

There is a wide variation (13% to 74%) in the reported prevalence of heart failure associated with normal left ventricular (LV) systolic function (diastolic heart failure). There is no published information on this condition in China. To ascertain the prevalence of diastolic heart failure in this community, 200 consecutive patients with the typical features of congestive heart failure were studied with standard 2-dimensional Doppler echocardiography. A LV ejection fraction (LVEF) >45% was considered normal. The results showed that 12.5% had significant valvular heart disease. Of the remaining 175 patients, 132 had a LVEF >45% (75%). Therefore, 66% of patients with a clinical diagnosis of heart failure had a normal LVEF. Heart failure with normal LV systolic function was more common than systolic heart failure in those >70 years old (65% vs 47%; p = 0.015). Most (57%) had an abnormal relaxation pattern in diastole and 14% had a restrictive filling pattern. In the systolic heart failure group, a restrictive filling pattern was more common (46%). There were no significant differences in the sex distribution, etiology, or prevalence of LV hypertrophy between these 2 heart failure groups. In conclusion, heart failure with a normal LVEF or diastolic heart failure is more common than systolic heart failure in Chinese patients with the symptoms of heart failure. This may be related to older age at presentation and the high prevalence of hypertension in this community.     

Clinical manifestations, diagnostic assessment, and etiology of heart failure in elderly patients

Heart failure in elderly patients may be difficult to diagnose because of a lack of typical symptoms and physical findings that are common in younger patients with this disorder. When present, the symptoms and signs are often nonspecific and mistakenly may be thought to be caused by other disorders that are commonly present in elderly patients. In older elderly patients, the symptoms and signs may be obscured by the presence of aging changes or other diseases. As a result of these problems, physicians must be highly suspicious of heart failure in all elderly patients who have underlying heart disease or who present with nonspecific symptoms that may represent heart failure. After the diagnosis of heart failure is established, the cause must be determined and systolic and diastolic ventricular dysfunction must be differentiated.     

舒张性与收缩性心力衰竭N末端心房利钠肽前体和N末端脑钠肽前体的研究

目的通过检测心力衰竭(心衰)患者血浆中N末端心房利钠肽前体(Nt-ProANP)和N末端脑钠肽前体(Nt-ProBNP)水平来鉴别舒张性心衰与收缩性心衰。方法选择心衰患者11 5例,其中收缩性心衰组76例,舒张性心衰组39例,另选健康体检者56例作为对照组。测定3组血浆Nt-ProANP和Nt-ProBNP水平。结果收缩性心衰组和舒张性心衰组Nt-ProANP、Nt-ProBNP水平明显高于对照组(P<0.01)。收缩性心衰组Nt-ProBNP水平明显高于舒张性心衰组,Nt-ProANP水平明显低于舒张性心衰组(P<0.05)。结论 Nt ProANP和Nt-ProBNP水平可用来鉴别收缩性心衰和舒张性心衰。     

Systolic and diastolic heart failure: Different phenotypes of the same disease?

Traditional pathophysiological concepts of chronic heart failure have largely focused on the haemodynamic consequences of ventricular systolic dysfunction. How these concepts relate to the pathophysiology of diastolic heart failure, i.e., heart failure with a preserved ejection fraction is, however, unclear, causing uncertainty about pathophysiology, diagnosis and management. Recent measurements of regional myocardial systolic function in patients with diastolic heart failure indicate that systolic and diastolic heart failure may be more closely related than previously anticipated. Rather than being considered as separate diseases with a distinct pathophysiology, systolic and diastolic heart failure may be merely different clinical presentations within a phenotypic spectrum of one and the same disease. In this review, we will interpret these new insights in a broader conceptual context of chronic heart failure and design novel paradigms in which systolic and diastolic heart failure jointly progress in a pathophysiological time trajectory of only one disease.     

Bradykinin improves left ventricular diastolic function under long-term angiotensin-converting enzyme inhibition in heart failure

Both systolic and diastolic cardiac dysfunction coexist in various degrees in the majority of patients with heart failure. Although ACE inhibitors are useful in the treatment of heart failure, the roles of bradykinin in the systolic and diastolic properties of left ventricular function under long-term treatment of ACE inhibitor have not been fully elucidated. We therefore evaluated the changes in left ventricular function, histomorphometry, and the expression of several failing heart related genes, by use of an orally active specific bradykinin type 2 receptor antagonist, FR173657 (0.3 mg/kg per day), with an ACE inhibitor, enalapril (1 mg/kg per day), in dogs with tachycardia-induced heart failure (270 ppm, 22 days) and compared the effects to enalapril alone. Although there were no differences observed in blood pressure, left ventricular dimension, and percentage of fractional shortening, FR173657 significantly increased left ventricular filling pressure (P<0.01), prolonged the time constant of relaxation (P<0.05), and suppressed the expression of endothelial NO synthase and sarcoplasmic reticulum Ca(2+)-ATPase mRNA (P<0.05). FR173657 also upregulated collagen type I and III mRNA (P<0.05) and increased the total amount of cardiac collagen deposits (P<0.05) in left ventricle compared with that in the enalapril-treated group. In conclusion, endogenous bradykinin contributes to the cardioprotective effect of ACE inhibitor, improving left ventricular diastolic dysfunction rather than systolic dysfunction, via modification of NO release and Ca(2+) handling and suppression of collagen accumulation.     

Doppler echocardiographic-guided diagnosis and therapy of heart failure

Abnormalities of diastolic function play a major role in producing the signs and symptoms of heart failure. In patients with heart failure and reduced left ventricular systolic function, concomitant diastolic dysfunction is invariably present. In addition, it is now well established that as many as 40% to 50% of patients with well-documented episodes of heart failure have preserved systolic function. Doppler echocardiography provides one of the most useful clinical tools for assessing left ventricular diastolic function and can provide diagnostic and prognostic information. The Doppler assessment of diastolic function should be part of the routine echocardiographic evaluation of patients suspected of having heart failure. This review focuses on the use of Doppler echocardiographic techniques to assess diastolic function. The Doppler patterns of diastolic filling observed and their progression over time in patients with myocardial disease are described and related to changes in the physiology of diastolic filling. In addition, Doppler echocardiographic-guided treatment strategies for heart failure are discussed.