Progression of Diastolic Dysfunction Predicts Incident Heart Failure

Abstract & Commentary

By Andrew J. Boyle, MBBS, PhD, Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco

Source: Kane GC, et al. Progression of left ventricular diastolic dysfunction and risk of heart failure. JAMA 2011;306:856-863.

Approximately half of all cases of heart failure occur in the context of normal systolic function (heart failure with preserved ejection fraction [HFPEF]) and the number of cases is projected to rise as the population ages. Diastolic dysfunction on echocardiography has been associated with HFPEF in cross-sectional studies. However, the effect of progression of diastolic dysfunction, assessed by serial echocardiograms, on the risk for subsequent heart failure is not known. Accordingly, Kane and colleagues studied the longitudinal changes in diastolic function over a 4-year period in a community cohort and then studied their incidence of heart failure in the subsequent 6 years.

In 1997, 4203 persons older than 45 years of age in Olmsted County, Minnesota, were invited to participate in the study. A total of 2042 participated in the first examination and 1402 returned for the subsequent examination 4 years later. Echocardiographic parameters of diastolic function included mitral inflow pulsed Doppler E/A ratio, pulmonary venous flow, and medial mitral annular tissue Doppler velocity. Participants were graded into four categories: normal diastolic function, mild, moderate, or severe diastolic dysfunction.

The mean age of the cohort was 65 years at the second visit, with 53% being younger than 65 years of age. More than 95% were white, 49% were male, and mean BMI was 28. Over the 4 years between the first and second echocardiogram, the prevalence of hypertension, diabetes, coronary artery disease, and heart failure all increased (P ≤ 0.001). Accordingly, more patients were also taking cardiac medications at the second examination, and the recorded blood pressure was actually lower at the second examination. Diastolic dysfunction prevalence increased from 24% to 39% (P < 0.001). The prevalence of systolic dysfunction did not change and the mean ejection fraction actually increased (63.9% vs 65.9%, P < 0.001). Individuals demonstrated worsening diastolic function in 23%, unchanged diastolic function in 68%, and improved diastolic function in 9%, and worsening of diastolic function was significantly associated with age > 65 years (odds ratio 2.85).

During 6.3 years of follow-up after the second echocardiogram, the development of heart failure correlated with diastolic function at echocardiogram 2. The incidence of heart failure was 2.6%, 7.8%, and 12.2% in persons with normal diastolic function, mild diastolic dysfunction, and moderate or severe diastolic dysfunction, respectively (P < 0.001). Multivariable analysis identified the following five independent predictors of incident heart failure: age (hazard ratio [HR] 8.38), hypertension (HR 2.21), coronary artery disease (HR 2.07), diastolic dysfunction (HR 1.81), and diabetes (HR 1.77). The authors conclude that in a population-based cohort undergoing 4 years of follow-up, the prevalence of diastolic dysfunction increased and that diastolic dysfunction was associated with development of heart failure during 6 years of subsequent follow-up.

Commentary

This longitudinal study demonstrates that over a short period of time (4 years), diastolic dysfunction occurred in nearly one-quarter of the cohort. This is a staggeringly high number in view of the fact that the majority of the cohort was younger than 65 years of age. In addition, the power of diastolic dysfunction to predict subsequent heart failure was of a similar order of magnitude to diabetes, hypertension, and coronary artery disease. This has prognostic implications not only for our elderly patients, but also for our middle-age patients. Unfortunately, the therapeutic implications remain unclear. Is there some way to impact the development of heart failure in patients diagnosed with diastolic dysfunction? Currently that remains unknown, and we can only control risk factors such as hypertension as best we can, and recommend adherence to diet and lifestyle modifications that are shown to be of long-term benefit.

This study is strengthened by the longitudinal nature of the serial echocardiographic evaluations. Furthermore, because Olmsted County residents are studied longitudinally, the authors were able to compare the outcomes of those who did not return for the second examination with those who did return. Nonreturners often confound observational studies, but not this study. Here, nonreturners had more co-morbidities and a higher subsequent mortality. Thus, the fact that they did not return for follow-up likely underestimated the effects of diastolic dysfunction on subsequent heart failure. There are several limitations to the study. First, the population was almost completely white, and so the results may not be generalizable to other populations. In fact, it would be reasonable to expect that the prevalence of diastolic dysfunction may be even higher in other ethnic or racial groups. Second, we are not told of how progression of diastolic dysfunction affects the risk of heart failure. The participants were classified according to their diastolic function at the second visit, not according to the change in diastolic function over the 4-year period. Thus, we are left to ponder the role of change in diastolic function in the management of these patients. Finally, we are not told what factors were associated with deteriorating or improving diastolic function. Do diet or lifestyle factors, obesity, or even medications change one's diastolic function over time? More study in this area is needed, but for now, we should consider diastolic dysfunction a marker of risk for heart failure and recommend adherence to diet and lifestyle factors that may improve outcomes.