Does Diastolic Heart Failure Really Exist?

Abstract & Commentary

An important publication by Zile and colleagues that have been long interested in diastolic properties of the heart, confirms that diastolic heart failure (DHF) is a real entity and is associated with significant abnormalities of active relaxation and passive stiffness in the left ventricle (LV). Zile et al performed a sophisticated analysis of 47 individuals with clinical diastolic heart failure (normal LV systolic function and CHF), using diagnostic cardiac catheterization with high-fidelity micromanometer catheters, and measurements of a variety of LV diastolic pressure and volume phenomena. The patients met criteria for congestive heart failure and had no secondary cause of cardiomyopathy. Echocardiographic markers of diastolic function were not used for patient selection. There were 31 men and 16 women with a mean age of 59 ± 12 years. Ten control patients undergoing cardiac catheterization for chest pain evaluation were also studied; all had normal coronary arteries. The protocol involved research quality measurements assessing diastolic stiffness with a variety of techniques, including estimation of diastolic left ventricular pressure and volume throughout the entire period of diastole. The investigators’ hypothesis was that patients with DHF would have an abnormally slow rate of ventricular relaxation, not allowing "full relaxation of the myocardium in early diastole." Thus, incomplete LV relaxation at the point of left ventricular minimal diastolic pressure would be a common denominator. Selected aspects of diastolic pressure-volume relationships, in addition to a number of calculated indices, including the corrected passive-stiffness constant, were measured. These included the time constants of isovolumic LV pressure decline (Tau); the minimal diastolic pressure pre A and post A wave; LV volume and mass; diastolic stiffness using pressure-volume coordinates; rate of relaxation, etc. The primary hypothesis was that the mean corrected stiffness constant in DHF patients would be 2 times as high as that of the control patients.

The results confirm Zile et al’s belief that diastolic heart failure is a valid phenomenon substantiated by their highly sophisticated LV pressure-volume measurements. Of note, not all DHF patients had echocardiographic left ventricular hypertrophy. Relaxation parameters were abnormal, including Tau, LV early minimal diastolic pressure, and the relationship between the two. "Thus, relaxation was incomplete at the time of LV minimal diastolic pressure. . . by contrast, relaxation was complete at the time of LV minimal diastolic pressure in all controls." DHF patients had higher end-diastolic pressures and lower LV volumes than controls, consistent with increased chamber stiffness. The diastolic pressure-volume relationship was displaced upward and to the left. Zile et al conclude that the hypothesis that increased diastolic pressures and clinical heart failure in individuals with a normal ejection fraction are directly related to abnormal diastolic properties of the LV; and that the term "diastolic heart failure" is appropriate. They point out that pulmonary congestion and symptoms of dyspnea, as well as fatigue, are probably related to elevations in systemic venous tone and arterial pressure, particularly when blood shifts to the central circulation, increasing LV diastolic pressure. They stress that such individuals are particularly vulnerable to developing pulmonary edema. The abnormal passive stiffness of the ventricle allows for small changes in volume to induce large changes in LV diastolic pressure. Increased filling pressures in the LV result in decreased pulmonary compliance, increased work of breathing, and dyspnea. Zile et al suggest that abnormal exercise tolerance may be due to the high LV filling pressures during exercise; these individuals "have little or no increase in stroke volume during exercise." In this report, 38% of patients had echocardiographic LV hypertrophy, 70% had hypertension. These values are in keeping with other recent reports of diastolic failure, showing a prevalence of LV hypertrophy of < 50% and a high likelihood of associated hypertension. They stress that LV hypertrophy, while common in DHF, is not required for the diagnosis of DHF. The LV volume in these individuals is characteristically small. They conclude that the term "diastolic heart failure" is appropriate, and that the hemodynamic abnormalities confirmed in this study directly point to abnormal LV active relaxation and increased passive stiffness.

An accompanying editorial by Margaret Redfield stresses that DHF patients tend to be older and more likely to be female than in systolic heart failure; coronary artery disease is not a primary factor, and most patients have coexisting hypertension. Atrial fibrillation, fluid overload, or poorly controlled hypertension are precipitating factors for heart failure as well as for the exercise intolerance. The mortality in diastolic heart failure is "nearly equivalent" to that ofsystolic heart failure, a finding that has been seen in other data sets. She makes the point that neurohormonal and other abnormalities that are well characterized in systolic heart failure have not been adequately investigated in DHF. Some investigators have been unable to confirm impaired LV relaxation, and have questioned whether DHF is a real entity; Redfield, as well as the authors of the primary paper, believe that this issue has been laid to rest. She stresses that "without a better understanding of the pathophysiology of diastolic heart failure, opportunities for new and potentially more effective strategies may be missed" (Zile MR, et al. N Engl J Med. 2004:350:1953-1959).

Comment by Jonathan Abrams, MD

This is an important investigation that confirms much previous data pointing to abnormal LV diastolic proper ties as being paramount in the causation of DHF. It is somewhat surprising to some, including myself, that diastolic heart failure carries a poor prognosis; the abnormalities described in this paper may help us to understand why prognosis is not benign. It is also important to note that echocardiographic LV hypertrophy is not a necessary component of DHF. Many individuals who have chronic kidney disease, particularly if they are on dialysis, will manifest diastolic heart failure. These patients may be particularly sensitive to volume changes with respect to clinical heart failure. In the absence of any overt clues leading to rare forms of heart failure, such as infiltrative disease, there appears to be no reason to perform myocardial biopsies or other studies; such individuals are probably more common than most physicians would realize. In summary, this is an elegant hemodynamic study in a substantial number of patients with apparently pure diastolic heart failure, which confirms that left ventricular relaxation and compliance properties are deranged in this condition. A common thread, other than the common association with hypertension, is not obvious. It is likely that the increased afterload of chronic hypertension alters LV myocardial function in individuals who manifest DHF. Therapy in these patients involves meticulous control of blood pressure and total body fluids; standard CHF drugs such as ACE inhibitors, beta-blockers, and even digoxin probably play a lesser role in treatment. Data on the most effective targeted treatments for DHF are lacking.

Jonathan Abrams, MD, Professor of Medicine, Division of Cardiology, University of New Mexico, Albuquerque, is a member of the Editorial Board of Clinical Cardiology Alert.