Use of Dynamic Myocardial Imaging in the Evaluation of Heart Failure With Preserved Ejection Fraction Provides Prognostic Value

A study published in JACC: Cardiovascular Imaging has shown that both left ventricular systolic and diastolic reserves contribute to risk prediction in Heart Failure With Preserved Ejection Fraction (HFpEF). Therefore, the inclusion of the exertional assessment of left ventricular function to diagnostic algorithms may improve the prognostication process in this disease condition.

With an ever-aging population, improvements in the treatment of atherosclerotic disease and hypertension, and increases in emerging risk factors such as diabetes and obesity, the prevalence and societal impact of HFpEF are now being well recognized. Previously, an impaired cardiovascular functional reserve was believed to contribute to adverse outcomes in HFpEF. However, the exact characteristics of pathophysiological profiles associated with increased clinical risk were still poorly defined. Thus, this study sought to determine the prognostic value of abnormal diastolic and systolic responses to exercise (on the basis of exertional E/e0 and global longitudinal strain rate [GSR]) in a well-characterized population of patients with heart failure with preserved ejection fraction (HFpEF). A complete echocardiogram (including assessment of myocardial deformation) was performed at rest in 205 patients (64 ± 8 years of age) with symptomatic HFpEF. Echocardiography following maximal exercise was undertaken to assess abnormal diastolic reserve (AbnDR) (exertional E/e0 >14) and exercise GSR. Patients were followed over 26 ± 5 months for death and cardiovascular or heart failure (HF) hospitalization. The results of the study showed that cardiovascular hospitalization or death occurred in 64 patients (31%), including 51 (25%) with HF hospitalization. The composite endpoint was associated with AbnDR (hazard ratio: 2.69; 95% confidence interval: 1.44 to 5.04; p ¼ 0.002) and reduced exercise GSR (hazard ratio: 0.14; 95% confidence interval: 0.04 to 0.49; p ¼ 0.002). Both exercise parameters showed prognostic value, independent from and incremental to clinical data and B-type natriuretic peptide. The ability of E/e0 and GSR measurements to predict outcomes on exertion exceeded their prognostic value at rest, and the presence of reduced exertional GSR in patients with AbnDR was associated with worse prognosis (p ¼ 0.03 for the composite endpoint and p ¼ 0.01 for HF hospitalization).

The team of investigators led by Dr. Thomas H. Marwick, Baker Heart and Diabetes Institute, Melbourne, Australia, concluded that the interplay of LV diastolic and systolic pathological features was associated with an increased likelihood of adverse outcomes in HFpEF. The assessment of LV diastolic and systolic responses to exercise by E/e0 and GSR could contribute to the improvement of risk prediction in this condition; however, further studies were warranted to refine the clinical application of exertional myocardial deformation measurements. Both LV diastolic and systolic abnormalities could be taken into account when planning outcome improving management strategies in HFpEF. This comprehensive approach including exercise evaluation could be helpful to optimize the design of future clinical studies of medication efficacy in HFpEF. In the context of this and previous results, the demonstrated association of LV exercise responses with increased CV risk supported the notion that limitations of the myocardial reserve may be considered as important targets and endpoint for phase 2 drug trials. Exercise echocardiography remains underused in patients with suspected HFpEF. These results support the wider consideration of this test.

Highlighting the importance of the study findings, Dr. Barry A. Borlaug from the Mayo Clinic and Foundation, Rochester, Minnesota wrote, “Kosmala et al. are to be commended for this important contribution, which adds significantly to a growing body of published studies on the utility of exercise testing in HFpEF by using both invasive and noninvasive modalities. Their data provide compelling support for the notion that myocardial reserve limitations play a central role in the pathophysiology of HFpEF. These data also suggest a potential role for stress testing in the classification scheme for HFpEF and support testing newer interventions that could improve ventricular and vascular reserve capacity. This study supports myocardial dynamic assessment to diagnose HFpEF, establish a prognosis, and perhaps even evaluate clinical course and response to therapeutic interventions.” However, emphasizing the role of future research, in an accompanying editorial titled ‘On Books, Covers, and Judgments in Heart Failure,’ Dr. Eric J. Velazquez commented, “With these findings, Kosmala et al. provide important data to support dynamic myocardial imaging for patients with HFpEF. Further study is needed to identify whether exercise testing in HFpEF has relevant pathological correlates when to use invasive and noninvasive modalities clinically and whether it can be used to inform responder status to available and emerging therapies. It is clear now more than ever that we cannot judge the book by its cover in HFpEF, but we do not yet know which tools will be best to help us read the fine print. That is the next question to be answered.”