Right Heart Phenotype in Heart Failure With Preserved Ejection Fraction

Abstract

The health burden of heart failure with preserved ejection fraction is increasingly recognized. Despite improvements in diagnostic algorithms and established knowledge on the clinical trajectory, effective treatment options for heart failure with preserved ejection fraction remain limited, mainly because of the high mechanistic heterogeneity. Diagnostic scores, big data, and phenomapping categorization are proposed as key steps needed for progress. In the meantime, advancements in imaging techniques combined to high-fidelity pressure signaling analysis have uncovered right ventricular dysfunction as a mediator of heart failure with preserved ejection fraction progression and as major independent determinant of poor outcome. This review summarizes the current understanding of the pathophysiology of right ventricular dysfunction in heart failure with preserved ejection fraction covering the different right heart phenotypes and offering perspectives on new treatments targeting the right ventricle in its function and geometry.

Keywords: heart failure with preserved ejection fraction; phenotype; pulmonary hypertension; right heart.

Figure 1.

Evolving stages in right ventricular (RV) geometry and functional changes based on the imposed hemodynamic loading. Pulmonary vascular resistance (PVR) and pulmonary arterial compliance (PCA) exhibit an inverse relationship described as PVR×PCA time constant, which broadly defines RV impedance. This time constant is affected by pulmonary artery wedge pressure (PAWP) shifting the relationship to the left as typically occurs in left-sided pulmonary hypertension. For PVR <3 WU, changes in time constant are primarily driven by the changes in pulsatile loading (impaired LA dynamics and increase in V wave with or without a specific contribution of mitral regurgitation and vascular venous pathology). Although vascular (veins and capillaries) disease injury (congestion and vasoconstriction) occurs even with normal PVR, for increasing PVR >3 WU, the time constant is highly affected by the resistive loading reflective of the remodeling process. The RV adapts and maladapts to impedance changes according to the Anrep and Starling laws with development of hypertrophy and dilatation. Changes in geometry combine with increased diastolic stiffness, favor tricuspid valve incompetence, and promote the interventricular septum position shift to the left yielding to a progressive loss of contractility and uncoupling with the pulmonary arterial circulation. ESV indicates end-systolic volume; LA, left atrium; LV, left ventricle; and WU, Wood unit.

Figure 2.

Studies on right ventricular (RV)–left ventricular (LV) diastolic ventricular interaction in heart failure with preserved ejection fraction (HFpEF). The increase in RV volume and pressure induced by exercise shifts the interventricular septum shifts toward the LV, distorting RV morphology, impairing filling, and decreasing contractile efficiency. The downstream effects of this sequence of events consist in an increased transmural pressure favored by the pericardium constraint. A, Early HFpEF studied during exercise. Reprinted from Parasuraman et al with permission. B, Obese HFpEF phenotype at rest. Reprinted from Obokata et al with permission. Copyright ©. C, Permanent atrial fibrillation (Perm AF) HFpEF phenotype as investigated at rest. Reprinted from Reddy et al with permission. Copyright © 2020, Elsevier. AF indicates atrial fibrillation; HT, hypertension; PCWP, pulmonary capillary wedge pressure; and RAP, right atrial pressure.

Figure 3.

Three-dimensional right heart echocardiography reconstruction and analyses Dimensional, functional, and geometric data of a healthy subject (A) versus a heart failure with preserved ejection fraction (HFpEF; B) and a pulmonary arterial hypertension (PAH) patient (C). Postprocessing analysis of nodes and colorimetric scale reconstruction of the right ventricular (RV) shape intriguingly shows that the main element in the normal RV function is the midposition of the septum with early HFpEF compared with control already shows some bulging of the septum in the left ventricle which is actually typical of PAH condition. EDV indicates end-diastolic volume; EDVi, end-diastolic volume indexed; EDSi, end-systolic volume indexed; EF, ejection fraction; ESV, end-systolic volume; SV, stroke volume.

Figure 4.

Representative cases of right ventricular (RV) dysfunction and RV–pulmonary circulation coupling phenotyping by tricuspid annular plane systolic excursion (TAPSE)/PASP ratio according to tertiles: 1, <0.35; 2, between 0.35 and 0.57; 3, >0.57. A cutoff of 0.36 has been documented by most studies as the most sensitive cutoff for prognostic definition. NT-proBNP indicates N-terminal pro-B-type natriuretic peptide; PASP, pulmonary arterial systolic pressure; PAWP, pulmonary artery wedge pressure; PVR, pulmonary vascular resistance; TR, tricuspid regurgitation; VCO2, carbon dioxide production; VE, ventilation; and VO2, oxygen consumption.

Figure 5.

Differences and clinical value of classical measures of right ventricle–pulmonary circulation coupling (end-systolic elastance [Ees]/arterial elastance [Ea]) and simplified surrogates (ejection fraction [EF] and ratios). ESP indicates end-systolic pressure; ESV, end-systolic volume; FAC, fractional area change; mPAP, mean pulmonary arterial pressure; PASP, pulmonary artery systolic pressure; RVEF, right ventricular ejection fraction; SV, stroke volume; and TAPSE, tricuspid annular plane systolic excursion.