Introduction:
Right ventricular (RV) failure due to pressure overload remains a clinical challenge, and current indices such as tricuspid annular plane systolic excursion (TAPSE) often fail to reflect disease severity. We aimed to delineate RV systolic and diastolic function in a preclinical model of pressure overload and translate these findings to patients undergoing transcatheter tricuspid intervention (TTVI).
Results:
In mice subjected to pulmonary artery banding (PAB) (N=25), increasing afterload led to a rise in contractility reflected by elevated end-systolic elastance (Ees), despite a significant reduction of TAPSE. Isolated RV cardiomyocytes from PAB mice exhibited impaired diastolic relaxation, characterized by prolonged time to baseline and increased diastolic cell length compared with controls, while systolic shortening remained unchanged. In vivo, PAB caused an enlarged right atrial (RA) area, consistent with elevated preload, which was associated with severe heart failure (HF) symptoms. Interestingly, TAPSE did not distinguish between mild and severe HF phenotypes. In contrast, diastolic indices (TV é, RVEDP) and RV free wall longitudinal strain were significantly worse in PAB mice with severe HF symptoms, with strain and é showing a negative correlation (r=-0.4039, p=0.0452), suggesting that RV free wall strain primarily reflects diastolic rather than systolic dysfunction in this model.
For a translational approach, we analyzed TTVI patients (N=138) from our center. In these patients, larger pre-interventional RA area correlated with reduced pre-interventional 6-minute walk distance (6MWD) (r=-0.2793, p=0.025), indicating that elevated preload is linked to impaired exercise capacity. At one-year follow-up, baseline RA area remained negatively correlated with 6MWD (r=-0.295, p=0.035). Notably, conventional systolic parameters such as TAPSE, FAC, or RVEF did not correlate with 6MWD at one year. These observations highlight that recovery from pressure (and volume) overload may not be adequately reflected by systolic indices alone, but rather by characterizing diastolic function, suggesting that diastolic properties could play a more pivotal role in patient outcomes than previously appreciated. Analyses on the influence of diastolic function are currently ongoing.
Conclusion:
The PAB model demonstrated that RV diastolic dysfunction and impaired longitudinal strain are key determinants of right-sided HF severity under pressure overload, whereas conventional systolic indices such as TAPSE fail to adequately capture these alterations. Additionally, RV strain provided an integrative measure of diastolic function and prognosis. In both datasets, RA dilation and, in the experimental data, diastolic dysfunction were associated with symptom burden, exercise limitation, and outcome, suggesting a similar relationship with diastolic function may be present in the clinical cohort. Consistently, our findings in TTVI patients confirmed that traditional systolic parameters did not predict patient outcome. Taken together, these results highlight the potential of RV strain and diastolic indices as superior markers of RV dysfunction and prognosis in right-sided HF, which will be the focus of further clinical analyses.
