Deterioration in right ventricular structure and function over time in patients with heart failure and preserved ejection fraction

Abstract

Aims: Prevalent right ventricular (RV) dysfunction (RVD) is associated with increased mortality in patients with heart failure with preserved ejection fraction (HFpEF), but no study has characterized long-term changes in RV structure and function within the same patient.

Methods and results: Patients with unequivocal HFpEF defined by either invasive haemodynamics or hospitalization for pulmonary oedema (n = 271) underwent serial echocardiographic evaluations >6 months apart. Clinical, structural, functional, and haemodynamic characteristics were examined. Over a median of 4.0 years (interquartile range 2.1-6.1), there was a 10% decline in RV fractional area change and 21% increase in RV diastolic area (both P < 0.0001). These changes greatly exceeded corresponding changes in the left ventricle. The prevalence of tricuspid regurgitation increased by 45%. Of 238 patients with normal RV function at Exam 1, 55 (23%) developed RVD during follow-up. Development of RVD was associated with both prevalent and incident atrial fibrillation (AF), higher body weight, coronary disease, higher pulmonary artery and left ventricular filling pressures, and RV dilation. Patients with HFpEF developing incident RVD had nearly two-fold increased risk of death (adjusted hazard ratio 1.89, 95% confidence interval 1.01-3.44; P = 0.04).

Conclusion: While previous attention has centred on the left ventricle in HFpEF, these data show that right ventricular structure and function deteriorate to greater extent over time when compared with changes in the left ventricle. Further study is required to evaluate whether interventions targeting modifiable risk factors identified for incident RVD, including abnormal haemodynamics, AF, coronary disease, and obesity, can prevent RVD and thus improve outcomes.

Keywords: Atrial fibrillation; HFpEF; Heart failure; Pulmonary hypertension; Right ventricle; Tricuspid regurgitation.

Figure 1

(A) Right ventricular dysfunction, defined by fractional area change <35% was markedly increased from Exam 1 to Exam 2 in patients with heart failure with preserved ejection fraction. (B) Compared with controls, patients with heart failure with preserved ejection fraction displayed greater decline in fractional area change. (C) The relationship between right ventricular fractional area change and estimated right ventricular systolic pressure shifted downward from Exams 1 to 2, indicating that the depression in right ventricular function was due to worsening myocardial dysfunction rather than greater afterload mismatch. (D) Right ventricular dilation was associated with right ventricular dysfunction in heart failure with preserved ejection fraction but not in controls. FAC, fractional area change; HFpEF, heart failure with preserved ejection fraction; RV, right ventricular.

Figure 2

Changes in structure and function in right ventricle in heart failure with preserved ejection fraction greatly exceeded those observed in the left ventricle. *P = 0.0001 between Exams 1 and 2; **P < 0.0001 between Exams 1 and 2.

Figure 3

(A) Prevalence of persistent atrial fibrillation was markedly increased in heart failure with preserved ejection fraction from Exams 1 to 2. (B and C) Heart failure with preserved ejection fraction patients who developed persistent atrial fibrillation displayed greater reduction in right ventricular fractional area change and more biatrial dilation than those who did not. (D) Development of incident persistent atrial fibrillation was associated with an increase in the prevalence of moderate-severe tricuspid regurgitation from 15% to 39%. #P < 0.001 vs. heart failure with preserved ejection fraction who did not develop persistent atrial fibrillation; ǂP = 0.03 vs. Exam 1. AF, atrial fibrillation; HFpEF, heart failure with preserved ejection fraction; LAVI, left atrial volume index; RA, right atrial; TR, tricuspid regurgitation.

Figure 4

(A) Compared with heart failure with preserved ejection fraction patients with normal right ventricular function at Exam 1, those with right ventricular dysfunction displayed increased mortality. (B) Of heart failure with preserved ejection fraction subjects with normal right ventricular function at baseline (n = 238), patients who developed right ventricular dysfunction had higher mortality rates than those who maintained right ventricular function overtime. HFpEF, heart failure with preserved ejection fraction; RVD, right ventricular dysfunction.

Take home figure

Right ventricular dysfunction develops over time in patients with heart failure with preserved ejection fraction that initially present with isolated left ventricular dysfunction, and changes in right ventricular structure and function greatly exceed changes observed in the left side of the heart in these more advanced phases of disease. Development of right ventricular dysfunction is related to elevated pulmonary artery and left heart filling pressures, as well as common comorbidities in heart failure with preserved ejection fraction including atrial fibrillation, coronary disease, and obesity. FAC, fractional area change; LVD, left ventricular dysfunction; RA, right atrial; RVD, right ventricular dysfunction; TR, tricuspid regurgitation.