By Michael H. Crawford, MD

Professor of Medicine, Associate Chief for Education, Division of Cardiology, University of California, San Francisco

Dr. Crawford reports no financial relationships relevant to this field of study.

SYNOPSIS: A retrospective longitudinal study of heart failure with preserved left ventricular ejection fraction shows that right ventricular function deteriorates more rapidly than left ventricular function and is associated with increased mortality.

SOURCES: Obokata M, Reddy YNV, Melenovsky V, et al. Deterioration in right ventricular structure and function over time in patients with heart failure and preserved ejection fraction. Eur Heart J 2019;40:689-697.

Gorter TM, van Veldhuisen DJ, Voors AA. Rapid right-sided deterioration in heart failure with preserved ejection fraction. Eur Heart J 2019;40:699-702.

The authors of previous cross-sectional studies have shown that right ventricular (RV) dysfunction in patients with heart failure with preserved left ventricular ejection fraction (HFpEF) is a strong predictor of morbidity and mortality. However, little is known about why some patients with HFpEF develop RV failure and some do not. Investigators from the Mayo Clinic performed a retrospective, longitudinal, observational study of patients with HFpEF confirmed by cardiac catheterization evidence of left heart filling pressures or HF symptoms (left ventricular ejection fraction ≥ 50%) and a previous hospitalization for pulmonary edema that resolved with diuretic therapy. Patients with significant valve disease, pulmonary disease, recent acute coronary syndrome, constrictive pericarditis, high output HF, or cardiomyopathy were excluded. Also, each patient had to have undergone two or more echocardiograms at least six months apart. In addition, 27 controls who demonstrated normal rest-exercise pulmonary capillary wedge pressures were used as a comparator group. Follow-up commenced after echo 2 in the 271 patients who met inclusion criteria. The median time between echo 1 and echo 2 was four years.

Between the two exams, blood pressure decreased, probably due to medication changes, but measures of LV diastolic function worsened. There was a small decline in LVEF, but LV volumes were unchanged. However, RV structure and function worsened significantly. RV diastolic area increased 20% and RV fractional area change (FAC) decreased 10%, such that there was a 2.5-fold increase in patients with RV dysfunction (FAC < 35%). Also, the right atrial area increased, and the prevalence of moderate-to-severe tricuspid valve regurgitation (TR) increased from 20% to 29% (P = 0.003), despite no change in estimated RV systolic pressure. No significant changes occurred in the control group in these measures over the same period.

Comparing those who maintained RV function to those who developed RV dysfunction, the latter group of patients were more likely to be overweight and diabetic. Atrial fibrillation, coronary artery disease, and higher RV systolic pressure (RVSP) and RV area also all were more common. However, there were no significant changes in LV systolic or diastolic function between the two groups. Over a median follow-up of 15 months, patients who exhibited RV dysfunction at exam 1 or who developed RV dysfunction between exam 1 and exam 2 were more likely to die (hazard ratio, 1.82; 95% confidence interval, 1.01-13.4; P = 0.04). The authors concluded that in patients with HFpEF, RV structure and function deteriorate to a much greater extent over time vs. LV structure and function.

COMMENTARY

In the first longitudinal study of the RV in patients with HFpEF, investigators used a unique retrospective design in select patients with at least two echoes from the Mayo Clinic cardiology database. The authors confirmed that the development of RV dysfunction increases mortality in HFpEF patients; surprisingly, this was not accompanied by a similar magnitude of worsening LV function. There are factors associated with this decline in RV function that are potentially modifiable (atrial fibrillation, obesity, and coronary artery disease). Although estimated RVSP was associated with worse RV function, as expected, it did not change significantly between the two exams despite markedly declining RV function.

From this study, three avenues emerge for preventing RV dysfunction from developing in HFpEF patients. First, keep RV pressure as low as possible by aggressive diuresis, perhaps guided by an implantable pulmonary artery pressure sensor. It is noteworthy in this study that only 40% of patients were on loop diuretics and 10% on aldosterone antagonists. Pulmonary vasodilators have been tried in pilot (Phase II) studies, and were negative to potentially harmful. In some situations, lowering pulmonary artery resistance results in too much blood flow to the lungs, which cannot be accommodated by the stiff LV resulting in acute pulmonary edema. Second, aggressively addressing the risk factors identified in this study could help. Third, there was significant progression of TR between the two exams without significant changes in RVSP. Procedures such as transcatheter clipping of the tricuspid valve leaflets may play a role in selected patients with moderate to severe TR and HFpEF.

Encourage patients to lose weight, try to keep them in sinus rhythm, and treat any myocardial ischemia. Further prospective data will be needed to establish the efficacy of these interventions, but there is little potential harm in trying them now.