Guideline-Directed Medical Therapy and Survival After TEER for Secondary Mitral Regurgitation With Right Ventricular Impairment.

BACKGROUND: Right ventricular impairment is common among patients undergoing transcatheter edge-to-edge repair for secondary mitral regurgitation (SMR). Adherence to guideline-directed medical therapy (GDMT) for heart failure is poor in these patients. OBJECTIVES: The aim of this study was to evaluate the impact of GDMT on long-term survival in this patient cohort. METHODS: Within the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) international registry, we selected patients with SMR and right ventricular impairment (tricuspid annular plane systolic excursion ≤17 mm and/or echocardiographic right ventricular-to-pulmonary artery coupling <0.40 mm/mm Hg). Titrated guideline-directed medical therapy (GDMTtit) was defined as a coprescription of 3 drug classes with at least one-half of the target dose at the latest follow-up. The primary outcome was all-cause mortality at 6 years. RESULTS: Among 1,213 patients with SMR and right ventricular impairment, 852 had complete data on medical therapy. The 123 patients who were on GDMTtit showed a significantly higher long-term survival vs the 729 patients not on GDMTtit (61.8% vs 36.0%; P < 0.00001). Propensity score-matched analysis confirmed a significant association between GDMTtit and higher survival (61.0% vs 43.1%; P = 0.018). GDMTtit was an independent predictor of all-cause mortality (HR: 0.61; 95% CI: 0.39-0.93; P = 0.02 for patients on GDMTtit vs those not on GDMTtit). Its association with better outcomes was confirmed among all subgroups analyzed. CONCLUSIONS: In patients with right ventricular impairment undergoing transcatheter edge-to-edge repair for SMR, titration of GDMT to at least one-half of the target dose is associated with a 40% lower risk of all-cause death up to 6 years and should be pursued independent of comorbidities.

Invasive Assessment of Right Ventricular to Pulmonary Artery Coupling Improves 1-year Mortality Prediction After Transcatheter Aortic Valve Replacement and Anticipates the Persistence of Extra-Aortic Valve Cardiac Damage.

Background: The interplay between the right ventricle and the pulmonary artery, known as right ventricular to pulmonary artery (RV-PA) coupling, is crucial for assessing right ventricular systolic function against the afterload from the pulmonary circulation. Pulmonary artery pressure levels are ideally measured by right heart catheterization. Yet, echocardiography represents the most utilized method for evaluating pulmonary artery pressure levels, albeit with limitations in accuracy. This study therefore aims to evaluate the prognostic significance of right ventricular to pulmonary artery (RV-PA) coupling expressed as tricuspid annular plane systolic excursion (TAPSE) related to systolic pulmonary artery pressure (sPAP) levels measured by right heart catheterization (TAPSE/sPAPinvasive) or estimated by transthoracic echocardiography (TAPSE/sPAPechocardiography) in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). Methods: Using data from a bicentric registry, this study compares TAPSE/sPAPinvasive vs. TAPSE/sPAPechocardiography in predicting 1-year all-cause mortality after TAVR. Results: Among 333 patients with complete echocardiography and right heart catheterization data obtained before TAVR, their mean age was 79.8 ± 6.74 years, 39.6% were female, and general 1-year survival was 89.8%. sPAPinvasive and sPAPechocardiography showed only moderate correlation (Pearson correlation coefficient R: 0.53, p value: <0.0001). TAPSE/sPAPinvasive was superior to TAPSE/sPAPechocardiography in predicting 1-year all-cause mortality after TAVR (area under the curve: 0.662 vs. 0.569, p value: 0.025). Patients with reduced TAPSE/sPAPinvasive levels (< 0.365 mm/mmHg) evidenced significantly lower 1-year survival rates than patients with preserved TAPSE/sPAPinvasive levels (81.8 vs. 93.6%, p value: 0.001; hazard ratio for 1-year mortality: 3.09 [95% confidence interval: 1.55-6.17]). Echocardiographic follow-up data revealed that patients with reduced RV-PA coupling suffer from persistent right ventricular dysfunction (TAPSE: 16.6 ± 4.05 mm vs. 21.6 ± 4.81 mm in patients with preserved RV-PA coupling) and severe tricuspid regurgitation (diagnosed in 19.7 vs. 6.58% in patients with preserved RV-PA coupling). Conclusions: RV-PA coupling expressed as TAPSE/sPAPinvasive can refine stratification of severe aortic stenosis patients into low-risk and high-risk cohorts for mortality after TAVR. Moreover, it can help to anticipate persistent extra-aortic valve cardiac damage, which will demand further treatment.

Artificial intelligence-enabled assessment of right ventricular to pulmonary artery coupling in patients undergoing transcatheter tricuspid valve intervention.

AIMS: Right ventricular to pulmonary artery (RV-PA) coupling has been established as a prognostic marker in patients with severe tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve interventions (TTVI). RV-PA coupling assesses right ventricular systolic function related to pulmonary artery pressure levels, which are ideally measured by right heart catheterization. This study aimed to improve the RV-PA coupling concept by relating tricuspid annular plane systolic excursion (TAPSE) to mean pulmonary artery pressure (mPAP) levels. Moreover, instead of right heart catheterization, this study sought to employ an extreme gradient boosting (XGB) algorithm to predict mPAP levels based on standard echocardiographic parameters. METHODS AND RESULTS: This multicentre study included 737 patients undergoing TTVI for severe TR; among them, 55 patients from one institution served for external validation. Complete echocardiography and right heart catheterization data were available from all patients. The XGB algorithm trained on 10 echocardiographic parameters could reliably predict mPAP levels as evaluated on right heart catheterization data from external validation (Pearson correlation coefficient R: 0.68; P value: 1.3 × 10-8). Moreover, predicted mPAP (mPAPpredicted) levels were superior to echocardiographic systolic pulmonary artery pressure (sPAPechocardiography) levels in predicting 2-year mortality after TTVI [area under the curve (AUC): 0.607 vs. 0.520; P value: 1.9 × 10-6]. Furthermore, TAPSE/mPAPpredicted was superior to TAPSE/sPAPechocardiography in predicting 2-year mortality after TTVI (AUC: 0.633 vs. 0.586; P value: 0.008). Finally, patients with preserved RV-PA coupling (defined as TAPSE/mPAPpredicted > 0.617 mm/mmHg) showed significantly higher 2-year survival rates after TTVI than patients with reduced RV-PA coupling (81.5% vs. 58.8%, P < 0.001). Moreover, independent association between TAPSE/mPAPpredicted levels and 2-year mortality after TTVI was confirmed by multivariate regression analysis (P value: 6.3 × 10-4). CONCLUSION: Artificial intelligence-enabled RV-PA coupling assessment can refine risk stratification prior to TTVI without necessitating invasive right heart catheterization. A comparison with conservatively treated patients is mandatory to quantify the benefit of TTVI in accordance with RV-PA coupling.

Right ventricular to pulmonary artery coupling and outcome in patients with cardiac amyloidosis.

AIMS: To investigate the prognostic value of the right ventricle-to-pulmonary artery (RV-PA) coupling in patients with either transthyretin (ATTR) or immunoglobulin light-chain (AL) cardiac amyloidosis (CA). METHODS AND RESULTS: Overall, 283 patients with CA from 3 Italian high-volume centres were included (median age 76 years; 63% males; 53% with ATTR-CA, 47% with AL-CA). The RV-PA coupling was evaluated by using the tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio. The median value of TAPSE/PASP was 0.45 (0.33-0.63) mm/mmHg. Patients with a TAPSE/PASP ratio <0.45 were older, had lower systolic blood pressure, more severe symptoms, higher cardiac troponin and N-terminal pro-B-type natriuretic peptide levels, greater left ventricular (LV) thickness, and worse LV systolic and diastolic function. A TAPSE/PASP ratio <0.45 was independently associated with a higher risk of all-cause death or heart failure (HF) hospitalization [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.32-2.96; P = 0.001] and all-cause death (HR 2.18, 95% CI 1.31-3.62; P = 0.003). The TAPSE/PASP ratio reclassified the risk of both endpoints [net reclassification index 0.46 (95% CI 0.18-0.74) P = 0.001 and 0.49 (0.22-0.77) P < 0.001, respectively], while TAPSE or PASP alone did not (all P > 0.05). The prognostic impact of the TAPSE/PASP ratio was significant both in AL-CA patients (HR for the composite endpoint 2.47, 95% CI 1.58-3.85; P < 0.001) and in ATTR-CA (HR 1.81, 95% CI 1.11-2.95; P = 0.017). The receiver operating characteristic curve showed that the optimal cut-off for predicting prognosis was 0.47 mm/mmHg. CONCLUSION: In patients with CA, RV-PA coupling predicted the risk of mortality or HF hospitalization. The TAPSE/PASP ratio was more effective than TAPSE or PASP in predicting prognosis.

Changes in Right Ventricular-to-Pulmonary Artery Coupling After Transcatheter Edge-to-Edge Repair in Secondary Mitral Regurgitation.

BACKGROUND: Preprocedural right ventricular-to-pulmonary artery (RV-PA) coupling is a major predictor of outcome in patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge mitral valve repair (M-TEER). However, clinical significance of changes in RV-PA coupling after M-TEER is unknown. OBJECTIVES: The aim of this study was to evaluate changes in RV-PA coupling after M-TEER, their prognostic value, and predictors of improvement. METHODS: This was a retrospective observational study, including patients undergoing successful M-TEER (residual mitral regurgitation ≤2+ at discharge) for SMR at 13 European centers and with complete echocardiographic data at baseline and short-term follow-up (30-180 days). RV-PA coupling was assessed with the use of echocardiography as the ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP). All-cause death was assessed at the longest available follow-up starting from the time of the echocardiographic reassessment. RESULTS: Among 501 patients included, 331 (66%) improved their TAPSE/PASP after M-TEER (responders) at short-term follow-up (median: 89 days; IQR: 43-159 days), whereas 170 (34%) did not (nonresponders). Lack of previous cardiac surgery, low postprocedural mitral mean gradient, low baseline TAPSE, high baseline PASP, and baseline tricuspid regurgitation were independently associated with TAPSE/PASP improvement after M-TEER. Compared with nonresponders, responders had lower New York Heart Association functional class and less heart failure hospitalizations at short-term follow-up. Improvement in TAPSE/PASP was independently associated with reduced risk of mortality at long-term follow-up (584 days; IQR: 191-1,243 days) (HR: 0.65 [95% CI: 0.42-0.92]; P = 0.017). CONCLUSIONS: In patients with SMR, improvement in TAPSE/PASP after successful M-TEER is predicted by baseline clinical and echocardiographic variables and postprocedural mitral gradient, and is associated with a better outcome.

Impact of Right Ventricular Dysfunction on Outcomes After Transcatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation.

OBJECTIVES: This study sought to assess the impact of right ventricular dysfunction (RVD) as defined by impaired right ventricular-to-pulmonary artery (RV-PA) coupling, on survival after edge-to-edge transcatheter mitral valve repair (TMVR) for severe secondary mitral regurgitation (SMR). BACKGROUND: Conflicting data exist regarding the benefit of TMVR in severe SMR. A possible explanation could be differences in RVD. METHODS: Using data from the EuroSMR (European Registry on Outcomes in Secondary Mitral Regurgitation) registry, this study compared the characteristics and outcomes of SMR patients undergoing TMVR, according to their RV-PA coupling, assessed by tricuspid annular plane systolic excursion-to-systolic pulmonary artery pressure (TAPSE/sPAP) ratio. RESULTS: Overall, 817 patients with severe SMR and available RV-PA coupling assessment underwent TMVR in the participating centers. RVD was present in 211 patients (25.8% with a TAPSE/sPAP ratio <0.274 mm/mm Hg). Although all patients demonstrated significant improvement in their New York Heart Association (NYHA) functional class, there was a trend toward a lower rate of NYHA functional class I or II among patients with RVD (56.5% vs. 65.5%, respectively; p = 0.086) after TMVR. Survival rates at 1 and 2 years were lower among patients with RVD (70.2% vs. 84.0%, respectively; p < 0.001; and 53.4% vs. 73.1%, respectively; p < 0.001). On multivariate analysis, a reduced TAPSE/sPAP ratio was a strong predictor of mortality (odds ratio: 1.62; 95% confidence interval: 1.14 to 2.31; p = 0.007). CONCLUSIONS: RVD, as shown by impairment of RV-PA coupling, is a major predictor of adverse outcome in patients undergoing TMVR for severe SMR. The often neglected functional and anatomic RV parameters should be systematically assessed when planning TMVR procedures for patients with severe SMR.