Right ventricle morphological and functional phenotypes in heart failure with reduced ejection fraction: from pathophysiology to prognostic significance
Authors: Frigelli M , Bandera F , D'Alesio G , Alfonzetti E , Mollo A , Sturla F , Votta E , Guazzi M 
Published: October 2021

Abstract

Background
Right ventricle (RV) remodeling is a marker of advanced disease and impaired prognosis in heart failure reduced ejection fraction (HFrEF) patients [1]. The assessment of RV remodeling is limited with standard echocardiography. Three-dimensional speckle-tracking echocardiography (3DSTE), with advanced post-processing, allows for RV shape and regional function assessment, potentially providing additional information [2].

Purpose
1) to describe global and regional RV shape and function in a HFrEF cohort of patients; 2) to define RV remodeling phenotypes according with pulmonary haemodynamics; 3) to test the prognostic significance of RV shape and functional parameters.

Methods
81 HFrEF patients were prospectively enrolled and followed-up (median time 760 days) for the composite end-point of death, heart failure hospitalization, heart transplant and left ventricular assist device implantation. They received standard 3DSTE evaluation, consisting of end-diastolic volume index (EDVi), end-systolic (ES) volume index (ESVi) and ejection fraction (EF) measurement via commercial software (TomTec Imaging Systems GmbH, Germany). Advanced post-processing provided RV free-wall and septal mean curvatures (Km) and minimum principal strain (MPS) [3] quantification. A subgroup of 40 subjects underwent right heart catheterization (RHC) and were classified in: group A – no pulmonary hypertension (PH) (n=15), group B – PH but normal pulmonary vascular resistance (PVR) (n=15) and group C – PH and increased PVR (n=10). Roc curves were used to identify RV parameters able to discriminate subjects belonging to group A. Prognostic significance of RV remodeling parameters was tested for the composite end-point.

Results
Patients who did receive RHC showed lower ES free-wall Km (0.052 vs 0.058 mm-1, p&lt;0.01) and impaired RV EF (35.9 vs 40.9%, p=0.04) if compared to those who didn't. A progressive RV dilatation, global and regional dysfunction were observed according with the degree of pulmonary haemodynamic worsening (ES free-wall Km 0.054, 0.052, 0.044 mm-1, p&lt;0.02 and free-wall MPS −23.1, −21.3, −19.2%, p&lt;0.02, for groups A, B and C, respectively, Fig. 1). RV ESVi, ES free-wall Km, global and regional MPS showed a good ability to discriminate patients without PH (ES free-wall MPS Sensitivity=0.72, 1-Specificity=0.4, area under curve=0.71). At univariable Cox Regression, the presence of more than moderate mitral regurgitation (MR), RV EF &lt;38% and free-wall MPS &gt;−22.4% (threshold discriminating normal pulmonary hemodynamic) resulted statistically associated with prognosis (Fig. 2).

Conclusion
In HFrEF patients, RV remodeling is progressively associated with unfavourable pulmonary haemodynamic, with a free-wall negative remodeling (abnormal curvature) resulting in loss of systolic function. RV free-wall function is tightly associated with the development of PH. 3DSTE indexes of RV global and regional function showed prognostic significance together with MR coexistence.

Funding Acknowledgement
Type of funding sources: Private hospital(s). Main funding source(s): IRCCS Policlinico San Donato is a clinical research hospital partially funded by the Italian Ministry of Health Figure 1. End-systolic MPS distributionFigure 2. Kaplan-Meier survival analysis