Epidemiological and case-control studies of heart failure estimate that systolic function is preserved in 40% to 50% of cases, which are thus presumed to be diastolic. However, the optimal treatment for diastolic heart failure has not yet been defined. Current American College of Cardiology/American Heart Association guidelines (Table I) emphasize the need to control the symptoms of diastolic heart failure by lowering left ventricular filling pressure without lowering cardiac output. This is important in that heart failure drugs have a narrow therapeutic window: an excessive reduction in preload can cause severe hypotension and low output.
Class I: diuretics and nitrates
Both drug classes are INDICATED. They lower high left ventricular filling pressure by decreasing systemic and pulmonary venous return, thus alleviating symptoms. If right heart dilatation is present, they decrease ventricular interdependence and the restrictive effect of the pericardium. Careful dosage modulation is important, given the frequent dependence of these patients on preload reserve. Despite their clear symptomatic benefits, the effects of these drugs on prognosis are still unknown.
Class II: (3-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors
Evidence for the efficacy of these POTENTIALLY USEFUL drugs remains inadequate. Though (3-blockade should lengthen ventricular relaxation a metabolically active process dependent on the efficacy of catecholamine-activated calcium reuptake by sarcoplasmic reticulum (3-blockers may also lower oxygen consumption (by slowing the heart rate), control hypertension, and inhibit ventricular hypertrophy and perhaps also fibrosis (two important determinants of diastolic dysfunction in coronary artery disease and hypertension). Moreover, like calcium channel blockers, (3-blockers control heart rate in atrial fibrillation, thus improving ventricular filling, which is notoriously hindered by the loss of atrial systole. Ongoing trials are investigating the efficacy of (3-blockade in heart failure with preserved systolic ventricular function. Calcium channel blockers act on diastolic dysfunction by controlling hypertension, lowering myocardial oxygen consumption, dilating the coronary microcirculation, and reversing hypertrophy. However, as with 13-blockers, their effects on survival and disease progression have yet to be determined.
Angiotensin-converting enzyme (ACE) inhibitors represent a major treatment strategy in systolic heart failure,
Class I Diuretics, nitrates, medications to control heart rate on atrial fibrillation, anticoagulants (if atrial fibrillation or past embolizations)
Class II Calcium channel blockers, (3-blockers, ACE inhibitors, anticoagulants for intracardiac thrombi
Class III Positive inotropes if no diastolic dysfunction, treatment of asymptomatic arrhythmias
Table I. Guidelines for the treatment of diastolic heart failure: American College of Cardiology/American Heart Association Task Force on Heart Failure.
After: Commitee on Evaluation and Management of Heart Failure. Guidelines for the evaluation and management of heart failure. Report of the Task force on Practice Guidelines. J Am Cell Cardiol. 1995;1376-1398. Copyright © 1995, Elsevier Science Ltd but are less frequently used in diastolic heart failure. Nevertheless, there is recent evidence of potential benefit. In the Vasodilator in Heart Failure Trials (V-HeFT), mortality in a small subgroup with heart failure and mild systolic dysfunction (ejection fraction [EF] >35%) treated with enalapril was lower not only than in patients with major systolic dysfunction, but also than in patients receiving hydralazine and isosorbide dinitrate. The lower mortality was due to a decrease in sudden deaths. The proposed mechanisms of these effects include the control of hypertension and reduction of ventricular mass in hypertensive patients, each of these factors being an important determinant of diastolic dysfunction. Ventricular hypertrophy secondary to pressure overload may also correlate with an increase in angiotensin II produced by the tissue ACE system, with secondary alteration of relaxation and increase of left ventricular filling pressure. Randomized multicenter studies of ACE inhibitors and angiotensin II receptor blockers, alone or in combination, are ongoing in populations with heart failure and preserved systolic function.
Bonow RO. Effects of calcium-chonnel blocking agents on left ventricular diastolic function in hypertrophic cardiomyopathy and in coronary artery disease. Am J Cardiol. 1985;55:172B-178B.
Bonow RO, Udelson JE. Left ventricular diastolic dysfunction as a cause of congestive heart failure. Mechanisms and management. Ann Intern Med. 1992;117:502-510.
Capasso JM, Puntillo E, Halpryn B, Olivetti G, Li P, Anversa P.
Amelioration of the effects of hypertension and diabetes on myocardium by cardiac glycoside. Am J Physiol. 1992;262:H734-H742.
Carroll JD, Lang RM, Neumann AL, Borow KM, Rajfer SI. The differential effects of positive inotropic and vasodilator therapy on diastolic properties in patients with congestive cardiomyopathy. Circulation. 1986;74:815-825.
Carson P, Johnson G, Fletcher R, Cohn J. Mild systolic dysfunction in heart failure (left ventricular ejection fraction > 35%); baseline characteristics, prognosis and response to therapy in the Vasodilator in Heart Failure Trials (V-HeFT). JAm Coll Cardiol. 1996;27:642-649 warrants further attention. It may be indicated in atrial fibrillation with high heart rate, either in replacement of, or in combination with p-blockers and calcium channel blockers. The Digitalis Investigation Group (DIG) trial in 1000 patients with heart failure and preserved systolic function (EF >40%) found that digoxin reduced hospitalization for heart failure, and possibly mortality, even in patients in sinus rhythm with a preserved ejection fraction. Digoxin may act on the determinants of passive myocardial elasticity by inhibiting collagen production and ventricular hypertrophy. It may also modulate baroreceptor and neurohumoral systems.
Current European Society of Cardiology guidelines for treating diastolic heart failure do not greatly differ from those itemized above: they are based on (5-blockers, diuretics, and ACE inhibitors. The best treatment is to act on the possible causes (eg, constrictive pericarditis) and potential aggravating factors (eg, coronary artery disease, tachycardia, supraventricular arrhythmias, hypertension, left ventricular hypertrophy). New drug therapy data will be available in a few years.
Committee on Evaluation and Management of Heart Failure.
Guidelines for the evaluation and management of heart failure. Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. JAm Coll Cardiol. 1995,26:1376-1398.
Krum H, Bigger JT, Goldsmith RL, Packer M. Effect of long-term digoxin therapy on autonomic function in patients with chronic heart failure. J Am Cardiol. 1995;25:289-294.
Ruzumna P, Gheorghiade M, Bonow RO. Mechanisms and management of heart failure due to diastolic dysfunction. Curr Opin Cardiol. 1996;11:269-275.
Senni M, Tribouilloy CM, Rodeheffer RJ, et al. Congestive heart failure in the community: a study of all incident cases in Olmsted County, Minnesota, in 1991. Circulation. 1998;98:2282-2289.
The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients witfi heart failure. N Engl J Med. 1997;336:525-533. Task Force of the Working Group on Heart Failure of the European Society of Cardiology. The treatment of heart failure. Eur Heart J. 1997,18:736-753.
drug; preserved systolic function; diuretic; nitrate; fi-blocker; calcium channel blocker; ACEI; vasodilator; positive inotrope
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