Adaptive versus maladaptive right ventricular remodelling

Abstract

Right ventricular (RV) function and its adaptation to increased afterload [RV–pulmonary arterial (PA) coupling] are crucial in various types of pulmonary hypertension, determining symptomatology and outcome. In the course of disease progression and increasing afterload, the right ventricle undergoes adaptive remodelling to maintain right‐sided cardiac output by increasing contractility. Exhaustion of compensatory RV remodelling (RV–PA uncoupling) finally leads to maladaptation and increase of cardiac volumes, resulting in heart failure. The gold‐standard measurement of RV–PA coupling is the ratio of contractility [end‐systolic elastance (Ees)] to afterload [arterial elastance (Ea)] derived from RV pressure–volume loops obtained by conductance catheterization. The optimal Ees/Ea ratio is between 1.5 and 2.0. RV–PA coupling in pulmonary hypertension has considerable reserve; the Ees/Ea threshold at which uncoupling occurs is estimated to be ~0.7. As RV conductance catheterization is invasive, complex, and not widely available, multiple non‐invasive echocardiographic surrogates for Ees/Ea have been investigated. One of the first described and best validated surrogates is the ratio of tricuspid annular plane systolic excursion to estimated pulmonary arterial systolic pressure (TAPSE/PASP), which has shown prognostic relevance in left‐sided heart failure and precapillary pulmonary hypertension. Other RV–PA coupling surrogates have been formed by replacing TAPSE with different echocardiographic measures of RV contractility, such as peak systolic tissue velocity of the lateral tricuspid annulus (S′), RV fractional area change, speckle tracking‐based RV free wall longitudinal strain and global longitudinal strain, and three‐dimensional RV ejection fraction. PASP‐independent surrogates have also been studied, including the ratios S′/RV end‐systolic area index, RV area change/RV end‐systolic area, and stroke volume/end‐systolic volume. Limitations of these non‐invasive surrogates include the influence of severe tricuspid regurgitation (which can cause distortion of longitudinal measurements and underestimation of PASP) and the angle dependence of TAPSE and PASP. Detection of early RV remodelling may require isolated analysis of single components of RV shortening along the radial and anteroposterior axes as well as the longitudinal axis. Multiple non‐invasive methods may need to be applied depending on the level of RV dysfunction. This review explains the mechanisms of RV (mal)adaptation to its load, describes the invasive assessment of RV–PA coupling, and provides an overview of studies of non‐invasive surrogate parameters, highlighting recently published works in this field. Further large‐scale prospective studies including gold‐standard validation are needed, as most studies to date had a retrospective, single‐centre design with a small number of participants, and validation against gold‐standard Ees/Ea was rarely performed.

Editors' highlight picks from 2023 in ESC heart failure

“…55 Besides genetic predispositions, epigenetic factors are considered to be detrimental during the course of HF specific myocardial remodelling via cardiomyocyte loss, interstitial fibrosis, vascular remodelling, 56 and for both the left and the right ventricles. 57 Short non-coding RNA molecules, called microRNAs (miRNAs) have the potential to regulate gene expression at the post-transcriptional level and thereby to contribute to the HF specific phenotype. In a recent review article of ESC Hert Failure, Gargiulo et al summarized the currently available information on the significance of miRNAs as biomarkers and potential therapeutic targets in patients with HF.…”

Comparison of prognostic value among echocardiographic surrogates of right ventricular–pulmonary arterial coupling: A three‐dimensional echocardiographic study

“…Other echocardiographic surrogates of RV–PA coupling have been also proposed by replacing TAPSE with RV systolic function parameters such as fractional area change (FAC), 14 RV strain, 15,16 and RV ejection fraction (RVEF) 16,17 . Furthermore, SV/ESV is a well‐known simplified index of RV–PA coupling, 3,18 where SV is stroke volume and ESV is end‐systolic volume in RV PV loops. Both SV and ESV can be measured non‐invasively using three‐dimensional (3D) echocardiography, and echocardiographic SV/ESV was associated with adverse events in pediatric PH patients 19 .…”

“…The adequacy of this RV adaptive response is commonly known as RV-pulmonary arterial (PA) coupling. 3 The gold-standard index of RV-PA coupling is the ratio between end-systolic elastance (contractility) and arterial elastance (afterload), derived from RV pressure-volume (PV) loops by right heart catheterization. However, PV loops are rarely measured in clinical settings due to their disadvantages: they require invasive, time-consuming, costly, and technically complex procedures.…”

“…However, PV loops are rarely measured in clinical settings due to their disadvantages: they require invasive, time-consuming, costly, and technically complex procedures. 3 Recently, non-invasive echocardiographic surrogates for RV-PA coupling have been investigated and reported to be useful in predicting clinical outcomes. One of the surrogates is the ratio between tricuspid annular plane systolic excursion (TAPSE) and estimated PA systolic pressure (PASP), which has been validated against gold-standard PV loops.…”

“…The RV is an afterload‐sensitive chamber, 2 and impaired adaption of RV contractility to afterload can lead to RV dysfunction or failure. The adequacy of this RV adaptive response is commonly known as RV–pulmonary arterial (PA) coupling 3 . The gold‐standard index of RV–PA coupling is the ratio between end‐systolic elastance (contractility) and arterial elastance (afterload), derived from RV pressure–volume (PV) loops by right heart catheterization.…”