Prognostic Value of Baseline Tricuspid Annular Plane Systolic Excursion to Pulmonary Artery Systolic Pressure Ratio in Mitral Transcatheter Edge-to-Edge Repair

Patients with severe mitral regurgitation (MR) frequently present with concomitant right ventricular (RV) dysfunction and tricuspid regurgitation (TR). We aimed to investigate the prognostic relevance of RV function, RV dimension, and TR in patients undergoing percutaneous intervention for MR. Consecutive patients undergoing percutaneous mitral valve intervention were enrolled in the prospective MitraSwiss registry. Tricuspid annular plane systolic excursion (TAPSE), pulmonary artery systolic pressure (PASP), right ventricular pulmonary arterial coupling (RVC, defined as TAPSE/ PASP ratio), indexed tricuspid annulus (TA) dimension, and TR severity grade were analyzed at baseline, post procedure, and at 6-month follow-up. The endpoints of all-cause mortality, hospitalization for heart failure, and the combined endpoint of the 2 were observed during long-term follow-up (up to 4 years). We analyzed 218 patients (mean age, 76 ± 9 years; 36% female). Edge-to-edge mitral valve repair resulted in an increase in TAPSE and RVC ratio and a decrease in indexed TA and PASP, but concomitant TR did not change significantly. In multivariable analysis, RV dysfunction and moderate/severe TR were independently associated with increased all-cause mortality (hazard ratio, 1.61; 95% confidence interval, 1.05-2.46; P=.03 and hazard ratio, 2.10; 95% confidence interval, 1.34-3.29; P<.01, respectively) and moderate/severe TR was further an independent predictor for hospitalization for heart failure and for the combined endpoint. Treatment of MR resulted in favorable changes of RV function and dimension but did not reduce TR in the majority of patients. TR at baseline remained the strongest predictor for outcomes, outperforming parameters of RV function and dimension.

Background: There is little evidence regarding mitral transcatheter edge-to-edge repair (TEER) in the setting of severe pulmonary hypertension (PH), defined by an estimated pulmonary arterial systolic pressure (PASP) &gt;70 mmHg on echocardiography. Objectives: To explore the prevalence of, and correlates and postprocedural outcomes associated with, severe PH in patients undergoing mitral TEER. Methods: We retrospectively evaluated a single-center registry of isolated, first-time interventions as a function of severe PH presence at baseline. Outcomes included all-cause mortality, heart failure (HF) hospitalizations, and the persistence of significant mitral regurgitation (MR) and functional impairment during the first postprocedural year. Results: A total of 1,182 individuals qualified for analysis. Of them, 100 (8.5%) had severe PH, demonstrating a median PASP of 78 (IQR, 75-85) mmHg. Compared to subjects free of severe PH, those with it exhibited a higher interventional risk, greater comorbidities, and more severe MR and cardiac dysfunction, and were more likely to undergo an urgent procedure. General interventional features were unaffected by severe PH status, leading in both study groups to a high (&gt;97%) technical success rate and, ultimately, significant improvement in PASP, MR grade and functional capacity. Severe PH was associated with worse residual MR in the total cohort – but not within a 187-patient, propensity score matched sub-cohort. In either, it did not impact the rate, cumulative incidence, and risk of mortality and/or HF hospitalizations. Conclusions: Mitral TEER in patients with severe PH should, in the hands of experienced interventionalists, prove feasible, safe, and efficacious.

There is little evidence regarding mitral transcatheter edge-to-edge repair (TEER) in the setting of severe pulmonary hypertension (PH), defined as an estimated pulmonary arterial systolic pressure (PASP) > 70 mmHg on echocardiography. We sought to explore the prevalence of, and correlates and postprocedural outcomes associated with, severe PH in patients undergoing mitral TEER. We retrospectively evaluated a single-center registry of isolated, first-time interventions as a function of severe PH presence at baseline. Outcomes included all-cause mortality, heart failure (HF) hospitalizations, and the persistence of significant mitral regurgitation (MR) and functional impairment during the first postprocedural year. A total of 1,182 individuals qualified for analysis. Of them, 100 (8.5%) had severe PH, demonstrating a median PASP of 78 (interquartile range, 75-85) mmHg. Compared to subjects free of severe PH, the former exhibited a higher interventional risk, a greater burden of comorbidities, and more severe MR and cardiac dysfunction, and were more likely to undergo an urgent procedure. General interventional features were unaffected by severe PH status, leading in both groups to a high (> 97%) technical success rate and, ultimately, significant improvements in PASP, MR grade and functional capacity. Severe PH was associated with worse residual MR in the total cohort - but not within a 187-patient, propensity score matched sub-cohort. In either, it did not correlate with the rate, cumulative incidence, and risk of mortality and/or HF hospitalizations. In our experience, severe PH preceding mitral TEER identified higher-risk patients but was unrelated to procedural feasibility, safety, or efficacy.

Right ventricular-pulmonary artery (RVPA) coupling is an emerging prognostic marker in cardiovascular disease, but its predictive value in patients undergoing mitral transcatheter edge-to-edge repair (MTEER) remains uncertain. We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. PubMed, Scopus, and Web of Science were searched for studies evaluating the prognostic impact of RVPA coupling in patients undergoing MTEER, using tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) or related markers. Risk of bias was assessed with the ROBINS-I tool, and meta-analyses were used to evaluate associations with clinical outcomes, including all-cause mortality, major adverse cardiovascular events (MACE), and residual mitral regurgitation (MR). Nine studies involving 3281 patients were included. Baseline RVPA uncoupling was significantly associated with an increased incidence of MACE (risk ratio [RR] 1.75, 95% confidence interval [CI]: 1.40-2.19) and higher all-cause mortality (RR 1.82, 95% CI: 1.53-2.18). No significant association was observed with post-operative MR (RR 1.17, 95% CI: 0.83-1.63). Sensitivity analyses did not alter the direction of the findings. RVPA uncoupling is associated with adverse outcomes after MTEER. Routine assessment may improve pre-procedural risk stratification. Further studies should refine diagnostic thresholds and evaluate potential therapeutic strategies in the setting of impaired RVPA coupling prior to MTEER.

Background Cardiac amyloidosis (CA) often leads to heart failure (HF) with preserved left ventricular ejection fraction, while also affecting right ventricular (RV) function and its ability to adapt to changes in afterload. Right ventricular-pulmonary arterial (RV-PA) coupling is a crucial indicator of this property, with its prognostic importance been recently investigated in various cardiovascular diseases. Purpose The aim of this systematic review and meta-analysis is to investigate the prognostic significance of RV-PA coupling in patients with CA. Methods We conducted a systematic literature search for studies assessing the prognostic role of RV-PA coupling in patients with CA. We recorded the method of RV-PA coupling assessment, the used cutoffs, patients’ age, sex, and follow-up duration. The outcomes of interest were all-cause mortality (ACM), cardiovascular mortality (CVM), hospitalization for HF (HHF), as well as combined endpoints (ACM+HHF, CVM+HHF) at maximal follow-up. We extracted the event rates for those endpoints according to RV-PA coupling, as defined by each study. Pooling of the risk ratios was conducted according to a random effects model. I2 was chosen as the measure of between-study heterogeneity, with values exceeding 50% being considered significant. Results We identified a total of 88 studies, of which 6 were ultimately selected for data extraction and inclusion in the meta-analysis after screening of title/abstract/full-text. All studies used the ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP), with cutoffs ranging from 0.31 to 0.47mm/mmHg. Studies included elderly patients with mean age exceeding 70 years, with male sex predominance. The follow-up duration ranged from 6 to 23 months. According to the results of the meta-analysis, compared to the RV-PA coupling group, the presence of RV-PA uncoupling was associated with high rates of ACM (RR: 2.07, 95% CI: 1.50-2.85, p&amp;lt;0.0001), CVM (RR: 2.97, 95% CI: 1.60-5.53, p=0.0006), and HHF (RR: 2.69, 95% CI: 1.28-5.66, p=0.009) (Figure 1). We also observed an increased incidence of the combined endpoints (ACM+HHF, RR: 1.97, 95% CI: 1.29-3.00, p=0.002; CVM+HHF, RR: 2.18, 95% CI: 1.50-3.18) (Figure 1). There was evidence of moderate between-study heterogeneity in almost all the performed analyses. Conclusion Our systematic review and meta-analysis highlight the prognostic impact of RV-PA uncoupling in patients with CA. RV-PA uncoupling through the TAPSE/PASP ratio was consistently associated with a higher risk of major adverse cardiovascular events, suggesting that it may serve as a valuable non-invasive marker for risk stratification in this high-risk population. However, the observed between-study heterogeneity underscores the need for further research to refine cutoff values and validate these findings in larger, prospective cohorts.Figure 1 Figure 2

Hemodynamic Impact and Outcome of Permanent Pacemaker Implantation Following Transcatheter Aortic Valve Implantation

Funding Acknowledgements Type of funding sources: None. Background in heart failure with reduced ejection fraction (HFrEF) the chronic increase of filling pressures progressively involves left atrium (LA), pulmonary circulation (PC) and right ventricle (RV), leading to worse outcome. Purpose we investigated the prognostic impact of either isolate LA impairment, RV dysfunction combined with pulmonary hypertension, or both, in HFrEF, using basic and advanced echocardiography. Methods 106 outpatients with HFrEF were enrolled. Exclusion criteria were primary lung disease, non-sinus rhythm, previous cardiac surgery, poor acoustic window. Clinical examination and basic echocardiography were performed. Speckle tracking analysis was used to measure peak atrial longitudinal strain (PALS) and a new marker of interaction between RV and PC: absolute free wall RV longitudinal strain(fwRVLS)/systolic pulmonary artery pressure(sPAP). Patients were followed for all-cause or cardiovascular death and heart failure (HF) hospitalization. Results of 84 eligible patients [mean age: 60.1 ± 11.5; 82% male, mean left ventricular ejection fraction (LV EF) 28 ± 5%], 48 reached the combined endpoint. Population was divided into 3 groups: Group 1 [PALS≥15 and fwRVLS/sPAP ≤ 0.5]; Group 2 [PALS ≤ 15 and fwRVLS/sPAP ≤ 0.5 or PALS≥15 and fwRVLS/sPAP≥0.5]; Group 3 [PALS ≤ 15 and fwRVLS/sPAP≥0.5]. Mean follow-up was 3.5 ± 0.3years. The increasing severity groups were associated with higher LA volume index (LAVI), New York Heart Association (NYHA) class, mitral regurgitation (MR) and tricuspid regurgitation (TR) grades, lower LV EF, LV global longitudinal strain (GLS), PALS, tricuspid annular plane systolic excursion (TAPSE), sPAP, fwRVLS and global RVLS(p &amp;lt; 0.0001). Reduced PALS and fwRVLS/sPAP were independent predictors of NYHA &amp;gt; 2 at univariate and multivariate analysis adjusted for age, sex, LV EF, and of any events with adjusted Cox models (Table 1). Kaplan-Meier curves showed a clear divergence between the groups for the prediction of the combined endpoint (Fig.1), cardiovascular death and HF hospitalization. Conclusions the combination of LA and RV damage could represent the transition point to end-stage HF, with considerably worse prognosis. Its assessment with PALS and fwRVLS/sPAP could help risk stratification of HFrEF patients in order to provide early treatment. Table 1 Unadjusted hazard ratio [95% CI] Adjusted for GLS hazard ratio [95% CI] Adjusted for GLS, LAVi, TR, RVFAC hazard ratio [95% CI] Group 3 vs 1 10.61 [4.16-27.06], p &amp;lt; 0.0001 10.24 [3.49-30.02], p &amp;lt; 0.0001 9.54 [2.95-30.92], p = 0.0002 Group 3 vs 2 3.90 [1.92-7.93], p = 0.0002 3.82 [1.74-8.36], p = 0.0008 3.78 [1.66-8.61], p = 0.002 Group 2 vs 1 2.72 [1.03-7.20], p = 0.04 2.69 [0.99-7.25], p = 0.05 2.53 [0.84-7.58], p = 0.1 CI, confidence interval; EF, ejection fraction; GLS, global longitudinal strain;LAVI, left atrial volume index; MR, mitral regurgitation, TR, tricuspid regurgitation Abstract Figure. Fig.1

Clinical and Hemodynamic Effects of Percutaneous Edge-to-Edge Mitral Valve Repair in Atrial Versus Ventricular Functional Mitral Regurgitation

Right ventricular-pulmonary arterial coupling in transcatheter structural heart interventions.

Prognostic Significance of Right Ventricular Dysfunction in Patients With Functional Mitral Regurgitation Undergoing MitraClip

Systolic pulmonary artery pressure (SPAP), tricuspid annular plane systolic excursion (TAPSE), and TAPSE/SPAP ratio trajectories are not fully characterized in chronic heart failure (HF). We assessed very long-term longitudinal SPAP, TAPSE and TAPSE/SPAP trajectories in HF patients, and their dynamic changes in outcomes. Prospective, consecutive, observational registry of real-life HF patients, performing echocardiography studies at baseline and according to a prospectively structured schedule after 1year, and then every 2 years, up to 15 years. Pulmonary hypertension (PH) was defined as SPAP ≥40 mmHg; right ventricular dysfunction (RVD) was defined at TAPSE ≤16 mm; and TAPSE/SPAP ratio was dichotomized at 0.36 mm/mmHg. The clinical endpoints were all-cause death, the composite endpoint of mortality or HF hospitalization and the number of recurrent HF hospitalizations. The study cohort included 1557 patients. Long-term SPAP trajectory Loess curves were U-shaped with a nadir at 7 years. TAPSE Loess curves showed a marked rise during the first year, with stabilization thereafter. TAPSE/SPAP ratio Loess splines were similar to the later with a smooth decline towards the end. Patients who died had higher SPAP, lower TAPSE and lower TAPSE/SPAP ratio in the preceding period than survivors. Baseline PH and/or RVD were independently associated with mortality and HF-related hospitalizations, and the persistence of one or both entities at 1year conferred a worse long-term prognosis. Long-term trajectories for SPAP, TAPSE and TAPSE/SPAP ratio are reported in patients with chronic HF. An increasing SPAP and declining TAPSE and TAPSE/SPAP ratio in the preceding period is associated with higher mortality.

Background Exercise-induced pulmonary hypertension, characterized by mean pulmonary artery pressure over cardiac output slope (mPAP/CO slope) &amp;gt; 3mmHg/L/min is associated with worse outcome in greater than moderate primary mitral regurgitation (PMR). However, the prognostic value of right ventricle to pulmonary artery coupling (RVPAc) is unknown. Purpose Assess the prognostic value of RVPAc; determine the additional value of exercise over rest RVPAc and compare these findings to the mPAP/CO slope. Methods The single center study included consecutive patients with greater than moderate PMR, no/discordant symptoms, left ventricular ejection fraction &amp;gt;60% and absence of concomitant valvular disease greater than moderate or permanent atrial fibrillation (AF) referred to simultaneous CPET and exercise echocardiography (CPET-echo). A thorough echocardiographic assessment of right ventricle (RV) systolic function and RVPAc (TAPSE/sPAP, ratio of tricuspid annular plane systolic excursion over systolic pulmonary artery pressure) was performed using a dedicated RV window. mPAP and CO were obtained by Doppler echocardiography. Primary outcome was the composite of cardiovascular mortality, unplanned cardiovascular hospitalization and new AF episodes. Results A total of 159 consecutive patients (64±11 years, 59% men) were included. The event-free survival rate was 84% at 1 year and 78% at 2 years. Patients who fulfilled the primary combined endpoint had significantly larger left atrium indexed volumes (LAVi), lower left atrial strain and strain rate at rest and strain at intermediate exercise, lower absolute and normalized peak oxygen uptake (VO2peak), and a significantly higher mPAP/CO slope. They had significantly lower TAPSE, RV free wall S’ and TAPSE/sPAP. Sequentially adding intermediate or high exercise TAPSE/sPAP and percent-predicted VO2peak to the baseline predictive model (age, LAVi, mitral regurgitation grade and TAPSE/sPAP at rest) significantly improved the area under the curve (AUC) of the baseline logistic regression model (AUC: 0.71 vs. 0.80 and 0.71 vs. 0.81, p&amp;lt;0.05, respectively), with LAVi and TAPSE/sPAP at intermediate or high exercise remaining as significant independent variables (although coupling assessment at high exercise technically less feasible). Replacing exercise TAPSE/sPAP with mPAP/CO yields models with comparable accuracy (Figure 1). Exercise TAPSE/sPAP &amp;lt;0,6 was related to a higher event rate (Figure 2) Conclusion Decreased rest or exercise TAPSE/sPAP are single point measures of RVPAc, associated with adverse outcome in patients with greater than moderate PMR and no or discordant symptoms. Exercise TAPSE/sPAP has independent additional value over rest TAPSE/sPAP in predicting adverse events, with a similar accuracy as mPAP/CO slope. Exercise TAPSE/sPAP represents a potential alternative to mPAP/CO slope in this population, being readily available and simpler to adopt in clinical practice.

Evolution of Functional Mitral Regurgitation and Prognosis in Medically Managed Heart Failure Patients With Reduced Ejection Fraction

Jumping down the rabbit hole: unravelling the right ventricle in heart failure.

Background Heart transplantation is sometimes the only therapeutic option in patients with advanced heart failure (HF), impaired ventricular function and significant functional or secondary mitral regurgitation (MR). The shortage of organs and the limitations of the recipient make it necessary to consider other therapeutic alternatives in these patients, such as mitral transcatheter edge-to-edge repair (M-TEER). The MitraBridge registry has recently been published in which they analyze the potential effect of M-TEER in patients with advanced HF and moderate-severe MI who are candidates for heart transplantation (mean age 59 years, left ventricular ejection fraction (LVEF) 27%); after a mean follow-up of 24 months, complete in 82.4%, they report an overall survival of 78.5%, a combined event-free survival of 47%, with a 6.5 % need for urgent transplantation and an HF hospitalization rate after M-TEER of 44/100 patient-years. The aim of our study is to assess the impact of M-TEER on mortality and the combined events of death, HF rehospitalization and the need for urgent transplantation or a ventricular assistance device in patients with moderate-severe functional MI and advanced HF who have also been evaluated for cardiac transplantation in our hospital. Methods This is a retrospective analysis of a prospective registry. Of the patients treated by M-TEER for severe MI, we selected those with advanced HF (defined as LVEF≤35%, and/or advanced functional class (NYHA III-IV)) who had also been evaluated as possible candidates for inclusion in the heart transplant list. Results From November 2011 to December 2023, 191 patients were treated by M-TEER, of whom 38 patients met the established criteria (median age 59 years [48-65], 31 (81%) males, mean LVEF was 26 ± 6%). All patients had at least one previous hospitalization for HF and optimal medical treatment according to guidelines; the rest of the baseline clinical characteristics are listed in Table 1. During the follow-up after M-TEER, with a median of 34 months [7-70], the probability of overall survival at 2 years was 75.6%. The combined endpoint of death, need for urgent transplantation or a ventricular assist device, and rehospitalization for heart failure occurred in 26 patients with a 2-year event-free survival probability of 48% (Figure 1). Five patients (13%) were transplanted, one (2.6%) urgently. Prior to M-TEER therapy, the rate of HF hospitalization was 108 hospitalizations/100 patient-years, which was significantly reduced after the procedure to 33 hospitalizations/100 patient-years (rate ratio 0.31 [95% CI 0.21-0.45, p&amp;lt;0.0005]). Conclusions In patients with advanced HF and severe functional MR who are candidates for cardiac transplantation, M-TEER is an effective therapeutic alternative, achieving a survival rate of more than three-quarters of the patients at 2 years of follow-up, a significant reduction in HF hospitalizations, and a low rate of need for cardiac transplantation.