Reduced tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) is a strong independent predictor of all-cause mortality and major adverse cardiovascular events (MACE) after intervention for aortic stenosis and mitral regurgitation, research published in JACC: Cardiovascular Interventions has shown.
This was among the conclusions of a systematic review and meta-analysis evaluating the prognostic power of right ventricle-pulmonary artery (RV-PA) coupling on adverse events after intervention for significant valvular heart disease.
Vitaliy Androshchuk (King’s College London, London, UK) and colleagues, who carried out the review, note in their JACC: Cardiovascular Interventions paper that right ventricular (RV) dysfunction has emerged as an important predictor of adverse outcomes following valvular heart intervention.
Invasive pressure-volume loop analysis—the reference standard for RV-PA coupling assessment—can detect subtle RV dysfunction but has limited clinical applicability due to its complexity, invasiveness, and cost, they write. Routine transthoracic echocardiography (TTE), however, provides rapid assessment of RV function and an estimate of PASP to derive a range of non-invasive surrogates of RV-PA coupling.
The authors of the review note that various studies have demonstrated the prognostic value of TAPSE/PASP in patients undergoing interventions for aortic stenosis, mitral regurgitation and tricuspid regurgitation, though several different RV-PA uncoupling thresholds have been reported. The systematic review and meta-analysis sought to determine the overall ability of TTE-derived RV-PA coupling to predict adverse clinical outcomes in patients undergoing valve intervention, and to establish specific thresholds to guide risk stratification.
Scouring electronic databases, the research team searched all relevant studies with subject headings and key words including valvular heart disease and RV-PA coupling. The primary outcome of the meta-analysis was all-cause mortality, with a secondary outcome a composite of major adverse cardiovascular events (MACE).
A total of 30 studies involving 12,992 patients fulfilled the eligibility criteria, with 14 interventional studies in patients with aortic stenosis, 12 in mitral regurgitation and four in tricuspid regurgitation, all considered to have low-to-moderate risk for bias.
Among the aortic stenosis intervention studies, the researchers note that there was substantial heterogeneity in the TAPSE/PASP cutoffs used to define RV-PA uncoupling, ranging from <0.290 to ≤0.590mm/mmHg, with TAPSE/PASP uncoupling associated with a significantly higher risk of all-cause mortality and MACE when evaluated as a categorical variable in unadjusted analyses. When adjusted for clinically relevant parameters, TAPSE/PASP uncoupling remained a significant independent predictor of all-cause mortality and the composite secondary endpoint, Androshchuk et al note.
Cut-off values of TAPSE/PASP used to define RV-PA uncoupling in mitral regurgitation intervention studies were generally lower compared with aortic stenosis, the analysis found, ranging from <0.274 to ≤0.370mm/mmHg. In unadjusted analysis, baseline TAPSE/PASP uncoupling was associated with significantly higher all-cause mortality and the composite secondary outcome. The risk of the composite secondary outcome increased substantially in a sensitivity analysis which excluded one study owing to a suggestion of publication bias, and significant and independent associations between TAPSE/PASP uncoupling, all-cause mortality and the composite secondary outcome remained after adjustment for clinically relevant confounders.
In studies of tricuspid regurgitation interventions, the study’s authors found that TAPSE/PASP cutoffs ranged from <0.317 to ≤0.460mm/mmHg and were independently associated with increased risk of all-cause mortality. Further quantitative meta-analysis of pooled effect estimates was not performed in this area due to the insufficient number of studies.
The findings lead Androshchuk et al to write that reduced TAPSE/PASP, which is indicative of RV-PA uncoupling, is a strong independent predictor of all-cause mortality and MACE after intervention for aortic stenosis and mitral regurgitation and has a significant non-linear association with adverse events following these procedures.
The optimum TAPSE/PASP threshold for outcome prediction following interventions for aortic stenosis was ≤0.51mm/mmHg for all-cause mortality and ≤0.49mm/mmHg for MACE, an approximately two-fold higher risk, they write. The threshold was lower for mitral interventions, at ≤0.33mm/mmHg for all-cause mortality and ≤0.36mm/mmHg for MACE, a three-fold higher risk. Finally, while there was insufficient evidence to estimate pooled effect sizes in tricuspid intervention cohorts, the researchers suggest that the data point to an optimal TAPSE/PASP threshold of ≤0.44mm/mmHg for all-cause mortality.
“Broadly interpreted, these data reinforce the evidence to support the clinical utility of non-invasive RV-PA coupling metrics and underscore the importance of evaluating RV function in patients with significant valvular heart disease,” Androshchuk and colleagues write. “To facilitate the clinical implementation of RV-PA coupling metrics, our findings establish optimum baseline TAPSE/PASP cutoff values that specifically define RV-PA uncoupling. By considering the disease-specific thresholds, TAPSE/PASP ratio can be integrated into risk stratification tools to improve risk prediction and guide periprocedural treatment decisions surrounding medical optimisation.”
Several limitations were noted by the authors, including the use of similar, but not identical, confounding variables in the selected studies, as well as different methodologies used to establish RV-PA cutoffs with the studies. Most of the included studies were observational, they note, which adds potential for confounding.
