Congestive heart failure may be considered a condition in which cardiac output is not adequate to meet the metabolic needs of the body, either at rest or with exercise, usually accompanied by an increase in cardiac filling pressure and / or volume.
Implicit in that physiological definition is that heart failure can be caused by an abnormality in systolic function leading to a defect in expulsion of the blood ( systolic heart failure ), or by an abnormality in diastolic function leading to a defect in ventricular filling ( diastolic heart failure ).
The former is the more familiar, classic heart failure in which an impaired inotropic state is responsible. Less familiar, but perhaps just as important, is diastolic heart failure, in which the ability of the ventricle(s) to accept blood is impaired. This problem is not rare, accounting in some series for as many as one third of patients presenting with heart failure.
Although the clinical manifestations of heart failure with and without systolic dysfunction are frequently very similar, the pathophysiological processes underlying the syndromes and consequently the treatment are quite different.
This article discusses pathophysiological, clinical, diagnostic and therapeutic aspects of this form of heart failure.
Pathophysiology and Clinical Expression
In marked contrast to the fundamental defect in systolic heart failure, patients with isolated diastolic heart failure have normal or often even enhanced contractile function of the left ventricle, which is intrinsically capable of responding normally to an increase in preload, and there is no undue sensitivity of systolic performance to increased afterload.
However, these patients also have dyspnea (shortness of breath) and fatigue, often as severe as that seen in patients with contractile dysfunction. The key problem in this syndrome is that ventricular stiffness or reduced compliance leads to limitations on the use of preload reserve because of rapid increases in cardiac filling pressures at normal or slightly increased cardiac volume. These effects limit cardiac output and cause dyspnea during exercise.
Classically, diastole has been subdived into four phases : isovolumic relaxation, a rapid-filling phase, a slow-filling phase and atrial systole. Isovolumic relaxation is the interval between aortic valve closure and mitral valve opening, during which ventricular pressure rapidly declines without a significant change in volume. This process is energy-dependent and may be very susceptible to cellular ischemia. Most ventricular filling then occurs during the subsequent rapid-filling phase, which also is at least partially energy-dependent.
As active relaxation ends and rapid-filling continues, further increases in ventricular size are limited by passive elements affecting stiffness of the myocardium. This third or slow-filling phase is primarily dependent upon these properties, which are not constant but may increase as left ventricular volume increases. Passive stiffness will be increased by fibrosis resulting from recurrent ischemia, infarction, or an infiltrating process.
Myocyte hypertrophy induced by poorly controlled hypertension or valvular disease may also result in an increase in stiffness. The last phase of diastole, atrial contraction, is normally responsible for 15-25% of the ventricular diastolic volume, but in certain disease states it can be as high as 40%.
The atrial contribution to ventricular filling will be greater in patients diminished early relaxation. The ventricular diastolic pressure / volume relationship may therefore be abnormal because of changes in active relaxation, passive compliance properties, or both. Whatever the specific abnormality, the final result is impaired ventricular filling and inappropriately elevated left atrial and pulmonary venous pressures.
Abnormal diastolic function may therefore cause symptoms of both dyspnea and fatigue secondary to an inadequate increase in cardiac output despite the presence of normal systolic function. If systolic function is also abnormal, these symptoms may be exaggerated. This may be a consideration when previously hypertrophied ventricles begin to fail ( as in progressive valvular disease, uncontrolled hypertension, or myocardial infarction ).
Under such circumstances, symptoms may be disproportionate to the degree of systolic dysfunction alone. This is probably not uncommon, since the same common diseases ( hypertension and coronary artery disease ) frequently leads to the syndrome of congestive heart failure, and may do so with varying contribution of the systolic and diastolic components if the systolic function is not normal.
Disease states associated with abnormal diastolic function may variably influence one or more of the aspects of diastolic function just discussed. Hypertrophy, the response of the ventricle to chronic pressure or volume overload, may be associated with both slowed active relaxation and increased passive chamber stiffness.
Myocardial ischemia causes transient changes in relaxation, and recurrent ischemia may result in chronic alterations of both relaxation and compliance. The infiltrating and restrictive cardiomyopathies ( sarcoidosis, hemochromatosis, amyloidosis ) are an uncommon cause of abnormal diastolic function, but when present may cause increased passive chamber stiffness from deposition of the implicated substance in the myocardium or interstitial space. Finally, ventricular diastolic properties are altered by aging independent of other disease processes. Relaxation is prolonged with increased age.
Differential Diagnosis and Clinical Evaluation
Table 1 lists clues to the diagnosis of
diastolic heart failure as offered by history, physical examination, ECG and chest roentgenogram. If systolic function is normal, additional steps must be taken to establish a diagnosis of
diastolic heart failure.
Exclusion of other causes of dyspnea on exertion is of first importance. Pulmonary disease, general physical deconditioning, valvular heart disease, systemic hypertension and intermittent ischemia all must be excluded. Once these are excluded, diastolic heart failure may be entertained, but preferably only after confirmation of an increase in capillary wedge or left ventricular end-diastolic pressures either at rest , during a volume load, or during exercise, since restriction to ventricular filling is the hallmark of this syndrome.
Measurements of diastolic function include the isovolumic relaxation time, the rate, duration, and fractional contribution of early and late diastolic filling, and pressure / volume curves that describe ventricular compliance. In the past , these parameters could only be obtained during invasive hemodynamic studies. Cardiac catheterization remains the best method to evaluate ventricular diastolic properties because pressure is directly measured. However, noninvasive methods, such as Echocardiography and radionuclide angiography, allow some inferential assessment of these same parameters.
Therapeutic Approaches
The therapeutic approach to diastolic dysfunction have has two major components. The first involves attempts to reverse the heart's abnormal diastolic properties; the second is directed toward reducing filling pressures and thereby venous congestion.
The patient with
diastolic heart failure is often functioning on a steep pressure-volume curve, and reduction in
diastolic pressure in such patients must be achieved with only small changes in volume. Goals should be to prevent left ventricular hypertrophy, treat elevated blood pressure, and preserve left ventricular filling. This may be achieved by maintaining sinus rhythm, slowing
heart rate and treating ischemia, which often may be effectively done as the other goals are accomplished.
Table 2 resumes the treatment of
diastolic heart failure.
Examples of the first approach include pericardiectomy for constrictive pericarditis, the relief of ventricular systolic overload, and the subsequent regression of ventricular hypertrophy. Efforts to achieve such regression involve the aggressive control of hypertension and the relief of valvular, subvalvular and supravalvular obstruction to ventricular outflow by operation or balloon dilatation. There is some evidence that ACE inhibitors and aldosterone antagonists slow, arrest or even reverse myocardial fibrosis in the presence of systolic overload, and these agents may be useful in the management of
diastolic dysfunction in these patients.
The rapid relief of acute myocardial ischemia is often effective when diastolic dysfunction is secondary to this condition. The reduction in heart rate caused by beta-blockers has several beneficial on diastolic function, including a prolongation of the filling period and an amelioration of ischemia. calcium channel blockers, especially Verapamil, have been shown to accelerate ventricular relaxation in patients with hypertrophic cardiomyopathy and have been reported to be useful in the treatment of diastolic dysfunction characteristic of this condition. Other beneficial mechanisms are reduction in heart rate, control of hypertension, reduced microvascular ischemia and oxygen demand, amelioration of intracellular calcium overload and regression of left ventricular hypertrophy.
Ventricular filling pressure and secondary venous congestion may be reduced by restriction of sodium intake and the administration of diuretics and venodilators. Even in the absence of ischemia, nitrates, by reducing preload, are useful in managing diastolic dysfunction and in the treatment and prevention of consequent severe pulmonary congestion. Nitroglycerin may be administered intravenously or sublingually in emergency situations, and long acting nitrates, such as isosorbide dinitrate, are often effective in the long term. In the long term, however, excessive preload reduction should be avoided because these patients often require higher-than-normal filling pressures to maintain an adequate stoke volume.
The maintenance of heart rhythm and rate is of critical importance. Tachycardia, whatever the underlying mechanism, must be controlled, thereby increasing the fraction of each cardiac cycle available for ventricular filling. Maintenance of sinus rhythm with synchronized atrioventricular sequential pacing may be crucial in permitting atrial augmentation of ventricular filling. Digoxin and other inotropic agents have no established place in these patients with relatively well preserved ejection fraction, and could, in principle, have an adverse effect in this group. Exercise training induces significant improvement in exercise capacity in patients with dilated cardiomyopathy and a pattern of abnormal left ventricular relaxation.
Finally, it has been shown that endogenous nitric oxide released from the coronary microcirculation selectively enhances left ventricular relaxation in the isolated ejecting guinea pig heart. These findings may lead to a new therapeutic approach to diastolic heart failure, with treatments aimed at the coronary microcirculation.
The American College of Cardiology / American Heart Association task force divides pharmacologic treatment into three classifications for the management of diastolic heart failure : Class I refers to drugs that are always indicated, such as diuretics and nitrates, and drugs suppressing atrioventricular conduction and anticoagulation if atrial fibrillation is present. Class II agents are " acceptable "; however, their efficacy is uncertain. These include calcium channel blockers, beta-blockers, ACE inhibitors and anticoagulation in patients with intracardiac thrombus. Class III drugs are not indicated and include drugs with positive inotropic effects.
