App-Based Mental Training to Reduce Atrial Fibrillation-Related Symptoms After Pulmonary Vein Isolation: MENTAL AF Trial.

BACKGROUND: Even after atrial fibrillation (AF) catheter ablation, many patients still experience relevant symptom burden. The objective of the MENTAL AF trial was to determine whether app-based mental training (MT) during the 3 months following pulmonary vein isolation reduces AF-related symptoms. METHODS AND RESULTS: Patients scheduled for pulmonary vein isolation were enrolled and randomized 1:1 to either app-based MT or usual care. Of 174 patients, 76 in the MT and 75 in the usual care group were included in the final analysis. The intervention was delivered by a daily 10-minute app-based MT. The primary outcome was the intergroup difference of the mean AF6 sum score, an AF-specific questionnaire, during the 3-month study period. Secondary outcomes included quality-of-life measures such as the AFEQT (Atrial Fibrillation Effect on Quality of Life). Mean age (SD) was 61 (8.7) years and 61 (41%) were women. The mean AF6 sum score over the study period was 8.9 (6.9) points in the MT group and 12.5 (10.1) in the usual care group (P=0.011). This referred to a reduction in the AF6 sum score compared with baseline of 75% in MT and 52% for usual care (P<0.001). The change in the AFEQT Global Score was 22.6 (16.3) and 15.7 (22.1), respectively; P=0.026. CONCLUSIONS: MENTAL AF showed that app-based MT as an adjunctive treatment tool following pulmonary vein isolation was feasible. App-based MT was found to be superior to standard care in reducing AF-related symptom burden and improving health-related quality of life. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04067427.

Effects of tricuspid transcatheter edge-to-edge repair on tricuspid annulus diameter - Data from the TriValve registry.

AIMS: T-TEER is an effective therapy for the treatment of tricuspid regurgitation (TR). However, the effects of leaflets clipping on tricuspid valve annulus (TA) have not been investigated in detail. The aim of this study is to investigate the effects of tricuspid transcatheter edge-to-edge repair (T-TEER) on TA diameter. METHODS AND RESULTS: The TriValve registry (Transcatheter Tricuspid Valve Therapies, NCT03416166) collected 556 patients from 22 European and North American centres undergoing transcatheter tricuspid valve interventions from 2016 to 2022. Patients undergoing T-TEER with available pre- and post-procedural data on TA diameter measured in the apical 4-chamber view on transthoracic echocardiography were selected for this study. Primary end-point was the reduction of TA diameter after T-TEER. A total of 186 patients were included in the study. In 115 patients (62%) TA diameter was reduced by at least 1 mm as compared to baseline. A significant reduction of TA dimension was observed following T-TEER (mean 2.3 mm [from pre-procedural diameter 46.7 mm to post-procedural diameter 44.4 mm], p < 0.001). In particular, the greatest reduction was observed in those with T-TEER in antero-septal commissure (mean 2.7 mm [from 47.1 mm to 44.4 mm], p < 0.001) as compared to those combining both antero-septal and postero-septal commissures (mean 1.4, from 46.0 mm to 44.6 mm, P = 0.06). A significant reduction of TA dimension was recorded in patients with 1 or 2 clips implanted but not in those patients with ≥3 clips implanted. CONCLUSIONS: In almost two third of patients T-TEER reduces TA diameter in addition to leaflet approximation. CONDENSED ABSTRACT: The effects of tricuspid transcatheter edge-to-edge repair (T-TEER) on tricuspid valve annulus (TA) have not been studied in details. This study investigates TA diameter as measured in apical 4-chamber view on transthoracic echocardiography before and after T-TEER. A total of 186 patients from the TriValve registry were included in the study. The study results show that 62% of patients have a TA reduction after T-TEER, especially in those receiving 1 or 2 clips in the antero-septal commissure. These suggest that T-TEER reduces tricuspid regurgitation not only by approximation of leaflets, but also by TA diameter reduction.

Impact of Contrast-Associated Acute Kidney Injury on One-Year Outcomes in Very Elderly STEMI Patients: Insights From a Multicenter Registry in Northern Italy.

Data about contrast-associated acute kidney injury (CA-AKI) in oldest old (age ≥85 years) ST-elevation myocardial infarction (STEMI) patients are scarce. We evaluated the incidence and the 1-year prognostic impact of CA-AKI in this population. Patients were included in a multicenter real-world registry, and CA-AKI was defined according to KDIGO (Kidney Disease Improving Global Outcomes) criteria. Major adverse cardiac and cerebrovascular events (MACCEs) were defined as the composite of all-cause death, stroke, unplanned coronary revascularization, and heart failure hospitalization. The primary outcome was the incidence and impact of CA-AKI on MACCEs at 1 year follow-up. Out of 461 STEMI patients (mean age 88.6 ± 2.9 years), 102 (22.1%) patients developed CA-AKI. Chronic kidney disease was the strongest predictor of CA-AKI (odds ratio [OR]: 4.52, 95% CI: 2.81-7.30, P < .01). The CA-AKI cohort showed a higher risk of MACCEs (adjusted HR: 1.75, 95% CI: 1.13-2.71, P = .01), driven mainly by all-cause death (adjusted hazard ratio [HR]: 2.39, 95% CI: 1.41-4.07, P = .01) and followed by heart failure hospitalization (adjusted HR: 2.01, 95% CI: 1.08-3.76, P = .01). Among oldest old STEMI, CA-AKI was frequent and associated with a higher incidence of MACCEs at 1-year follow-up.

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.

Treatment response to spironolactone in patients with heart failure with preserved ejection fraction: a machine learning-based analysis of two randomized controlled trials.

BACKGROUND: Whether there is a subset of patients with heart failure with preserved ejection fraction (HFpEF) that benefit from spironolactone therapy is unclear. We applied a machine learning approach to identify responders and non-responders to spironolactone among patients with HFpEF in two large randomized clinical trials. METHODS: Using a reiterative cluster allocating permutation approach, patients from the derivation cohort (Aldo-DHF) were identified according to their treatment response to spironolactone with respect to improvement in E/e'. Heterogenous features of response ('responders' and 'non-responders') were characterized by an extreme gradient boosting (XGBoost) algorithm. XGBoost was used to predict treatment response in the validation cohort (TOPCAT). The primary endpoint of the validation cohort was a combined endpoint of cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization. Patients with missing variables for the XGboost model were excluded from the validation analysis. FINDINGS: Out of 422 patients from the derivation cohort, reiterative cluster allocating permutation identified 159 patients (38%) as spironolactone responders, in whom E/e' significantly improved (p = 0.005). Within the validation cohort (n = 525) spironolactone treatment significantly reduced the occurrence of the primary outcome among responders (n = 185, p log rank = 0.008), but not among patients in the non-responder group (n = 340, p log rank = 0.52). INTERPRETATION: Machine learning approaches might aid in identifying HFpEF patients who are likely to show a favorable therapeutic response to spironolactone. FUNDING: See Acknowledgements section at the end of the manuscript.

Stressed Blood Volume in Severe Tricuspid Regurgitation: Implications for Transcatheter Treatment.

BACKGROUND: Although tricuspid transcatheter edge-to-edge repair (TEER) has been suggested to improve outcomes in patients with tricuspid regurgitation (TR), patients remain at substantial residual risk after the intervention. Total blood volume is divided between the unstressed volume, filling the vascular space, and stressed blood volume (SBV), generating intravascular pressure. SBV is an important mediator of hemodynamic derangements in heart failure and might pose an attractive adjunctive treatment target. OBJECTIVES: The aim of this study was to investigate the role of SBV in patients with severe TR and its implications for tricuspid TEER. METHODS: In total, 279 patients underwent right heart catheterization prior to TEER. SBV was estimated from hemodynamic variables fit to a comprehensive cardiovascular model. RESULTS: Estimated stressed blood volume (eSBV) was associated with obesity, renal and hepatic dysfunction and cardiac remodeling (P < 0.05 for all). Hemodynamically, eSBV correlated with pulmonary artery and cardiac filling pressures as well as right ventricular-pulmonary artery coupling (P < 0.05 for all). After TEER, patients with eSBV greater than the median demonstrated less reduction in right atrial pressures, peripheral edema, and ascites compared with lower eSBV patients (P < 0.05 for all). Higher eSBV was an independent predictor of the occurrence of death and heart failure hospitalization during a median follow-up duration of 618 days (P < 0.05 for all). CONCLUSIONS: In patients with severe TR, eSBV is associated with obesity, renal and liver dysfunction, more severe heart failure, attenuated reduction of venous congestion after TEER, and adverse clinical outcomes. Estimation of SBV should be incorporated in future trials in the field to identify patients in need of adjunctive therapies.

Sex-Related Differences in Clinical Characteristics and Outcome Prediction Among Patients Undergoing Transcatheter Tricuspid Valve Intervention.

BACKGROUND: Men and women differ regarding comorbidities, pathophysiology, and the progression of valvular heart diseases. OBJECTIVES: This study sought to assess sex-related differences regarding clinical characteristics and the outcome of patients with severe tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve intervention (TTVI). METHODS: All 702 patients in this multicenter study underwent TTVI for severe TR. The primary outcome was 2-year all-cause mortality. RESULTS: Among 386 women and 316 men in this study, men were more often diagnosed with coronary artery disease (52.9% in men vs 35.5% in women; P = 5.6 × 10-6). Subsequently, the underlying etiology for TR in men was predominantly secondary ventricular (64.6% in men vs 50.0% in women; P = 1.4 × 10-4), whereas women more often presented with secondary atrial etiology (41.7% in women vs 24.4% in men, P = 2.0 × 10-6). Notably, 2-year survival after TTVI was similar in women and men (69.9% in women vs 63.7% in men; P = 0.144). Multivariate regression analysis identified dyspnea expressed as New York Heart Association functional class, tricuspid annulus plane systolic excursion (TAPSE), and mean pulmonary artery pressure (mPAP) as independent predictors for 2-year mortality. The prognostic significance of TAPSE and mPAP differed between sexes. Consequently, we looked at right ventricular-pulmonary arterial coupling expressed as TAPSE/mPAP and identified sex-specific thresholds to best predict survival; women with a TAPSE/mPAP ratio <0.612 mm/mm Hg displayed a 3.43-fold increased HR for 2-year mortality (P < 0.001), whereas men with a TAPSE/mPAP ratio <0.434 mm/mm Hg displayed a 2.05-fold increased HR for 2-year mortality (P = 0.001). CONCLUSIONS: Even though men and women differ in the etiology of TR, both sexes show similar survival rates after TTVI. The TAPSE/mPAP ratio can improve prognostication after TTVI, and sex-specific thresholds should be applied to guide future patient selection.

Epiphenomenon or Prognostically Relevant Interventional Target? A Novel Proportionality Framework for Severe Tricuspid Regurgitation.

Background Tricuspid regurgitation (TR) frequently develops in patients with long-standing pulmonary hypertension, and both pathologies are associated with increased morbidity and mortality. This study aimed to improve prognostic assessment in patients with severe TR undergoing transcatheter tricuspid valve intervention (TTVI) by relating the extent of TR to pulmonary artery pressures. Methods and Results In this multicenter study, we included 533 patients undergoing TTVI for moderate-to-severe or severe TR. The proportionality framework was based on the ratio of tricuspid valve effective regurgitant orifice area to mean pulmonary artery pressure. An optimal threshold for tricuspid valve effective regurgitant orifice area/mean pulmonary artery pressure ratio was derived on 353 patients with regard to 2-year all-cause mortality and externally validated on 180 patients. Patients with a tricuspid valve effective regurgitant orifice area/mean pulmonary artery pressure ratio ≤1.25 mm2/mm Hg (defining proportionate TR) featured significantly lower 2-year survival rates after TTVI than patients with disproportionate TR (56.6% versus 69.6%; P=0.005). In contrast with patients with disproportionate TR (n=398), patients with proportionate TR (n=135) showed more pronounced mPAP levels (37.9±9.06 mm Hg versus 27.9±8.17 mm Hg; P<2.2×10-16) and more severely impaired right ventricular function (tricuspid annular plane systolic excursion: 16.0±4.11 versus 17.0±4.64 mm; P=0.012). Moreover, tricuspid valve effective regurgitant orifice area was smaller in patients with proportionate TR when compared with disproportionate TR (0.350±0.105 cm2 versus 0.770±0.432 cm2; P<2.2×10-16). Importantly, proportionate TR remained a significant predictor for 2-year mortality after adjusting for demographic and clinical variables (hazard ratio, 1.7; P=0.006). Conclusions The proposed proportionality framework promises to improve future risk stratification and clinical decision-making by identifying patients who benefit the most from TTVI (disproportionate TR). As a next step, randomized controlled studies with a conservative treatment arm are needed to quantify the net benefit of TTVI in patients with proportionate TR.

A cardiologist's guide to machine learning in cardiovascular disease prognosis prediction.

A modern-day physician is faced with a vast abundance of clinical and scientific data, by far surpassing the capabilities of the human mind. Until the last decade, advances in data availability have not been accompanied by analytical approaches. The advent of machine learning (ML) algorithms might improve the interpretation of complex data and should help to translate the near endless amount of data into clinical decision-making. ML has become part of our everyday practice and might even further change modern-day medicine. It is important to acknowledge the role of ML in prognosis prediction of cardiovascular disease. The present review aims on preparing the modern physician and researcher for the challenges that ML might bring, explaining basic concepts but also caveats that might arise when using these methods. Further, a brief overview of current established classical and emerging concepts of ML disease prediction in the fields of omics, imaging and basic science is presented.

Prognostic Value of Tricuspid Valve Gradient After Transcatheter Edge-to-Edge Repair: Insights From the TriValve Registry.

BACKGROUND: Data regarding the impact of the tricuspid valve gradient (TVG) after tricuspid transcatheter edge-to-edge repair (TEER) are scarce. OBJECTIVES: This study sought to evaluate the association between the mean TVG and clinical outcomes among patients who underwent tricuspid TEER for significant tricuspid regurgitation. METHODS: Patients with significant tricuspid regurgitation who underwent tricuspid TEER within the TriValve (International Multisite Transcatheter Tricuspid Valve Therapies) registry were divided into quartiles based on the mean TVG at discharge. The primary endpoint was the composite of all-cause mortality and heart failure hospitalization. Outcomes were assessed up to the 1-year follow-up. RESULTS: A total of 308 patients were included from 24 centers. Patients were divided into quartiles of the mean TVG as follows: quartile 1 (n = 77), 0.9 ± 0.3 mm Hg; quartile 2 (n = 115), 1.8 ± 0.3 mm Hg; quartile 3 (n = 65), 2.8 ± 0.3 mm Hg; and quartile 4 (n = 51), 4.7 ± 2.0 mm Hg. The baseline TVG and the number of implanted clips were associated with a higher post-TEER TVG. There was no significant difference across TVG quartiles in the 1-year composite endpoint (quartiles 1-4: 35%, 30%, 40%, and 34%, respectively; P = 0.60) or the proportion of patients in New York Heart Association class III to IV at the last follow-up (P = 0.63). The results were similar after adjustment for clinical and echocardiographic characteristics (composite endpoint quartile 4 vs quartile 1-quartile 3 adjusted HR: 1.05; 95% CI: 0.52-2.12; P = 0.88) or exploring post-TEER TVG as a continuous variable. CONCLUSIONS: In this retrospective analysis of the TriValve registry, an increased discharge TVG was not significantly associated with adverse outcomes after tricuspid TEER. These findings apply for the explored TVG range and up to the 1-year follow-up. Further investigations on higher gradients and longer follow-up are needed to better guide the intraprocedural decision-making process.

Staging Heart Failure Patients With Secondary Mitral Regurgitation Undergoing Transcatheter Edge-to-Edge Repair.

BACKGROUND: Secondary mitral regurgitation (SMR) is a progressive disease with characteristic pathophysiological changes that may influence prognosis. Although the staging of SMR patients suffering from heart failure with reduced ejection fraction (HFrEF) according to extramitral cardiac involvement has prognostic value in medically treated patients, such data are so far lacking for edge-to-edge mitral valve repair (M-TEER). OBJECTIVES: This study sought to classify M-TEER patients into disease stages based on the phenotype of extramitral cardiac involvement and to assess its impact on symptomatic and survival outcomes. METHODS: Based on echocardiographic and clinical assessment, patients were assigned to 1 of the following HFrEF-SMR groups: left ventricular involvement (Stage 1), left atrial involvement (Stage 2), right ventricular volume/pressure overload (Stage 3), or biventricular failure (Stage 4). A Cox regression model was implemented to investigate the impact of HFrEF-SMR stages on 2-year all-cause mortality. The symptomatic outcome was assessed with New York Heart Association functional class at follow-up. RESULTS: Among a total of 849 eligible patients who underwent M-TEER for relevant SMR from 2008 until 2019, 9.5% (n = 81) presented with left ventricular involvement, 46% (n = 393) with left atrial involvement, 15% (n = 129) with right ventricular pressure/volume overload, and 29% (n = 246) with biventricular failure. An increase in HFrEF-SMR stage was associated with increased 2-year all-cause mortality after M-TEER (HR: 1.39; CI: 1.23-1.58; P < 0.01). Furthermore, higher HFrEF-SMR stages were associated with significantly less symptomatic improvement at follow-up. CONCLUSIONS: The classification of M-TEER patients into HFrEF-SMR stages according to extramitral cardiac involvement provides prognostic value in terms of postinterventional survival and symptomatic improvement.

Sex-related characteristics and short-term outcomes of patients undergoing transcatheter tricuspid valve intervention for tricuspid regurgitation.

AIMS: The impact of sexuality in patients with significant tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve intervention (TTVI) is unknown. The aim of this study was to investigate sex-specific outcomes in patients with significant TR treated with TTVI vs. medical therapy alone. METHODS AND RESULTS: The Transcatheter Tricuspid Valve Therapies (TriValve) registry collected data on patients with significant TR from 24 centres who underwent TTVI from 2016 to 2021. A control cohort was formed by medically managed patients with ≥severe isolated TR diagnosed in 2015-18. The primary endpoint was freedom from all-cause mortality. Secondary endpoints were heart failure (HF) hospitalization, New York Heart Association (NYHA) functional status, and TR severity. One-year outcomes were assessed for the TriValve cohort and compared with the control cohort with the inverse probability of treatment weighting (IPTW). A total of 556 and 2072 patients were included from the TriValve and control groups, respectively. After TTVI, there was no difference between women and men in 1-year freedom from all-cause mortality 80.9% vs. 77.9%, P = 0.56, nor in HF hospitalization (P = 0.36), NYHA Functional Classes III and IV (P = 0.17), and TR severity >2+ at last follow-up (P = 0.42). Multivariable Cox-regression weighted by IPTW showed improved 1-year survival after TTVI compared with medical therapy alone in both women (adjusted hazard ratio 0.45, 95% confidence interval 0.23-0.83, P = 0.01) and men (adjusted hazard ratio 0.42, 95% confidence interval 0.18-0.89, P = 0.03). CONCLUSION: After TTVI in high-risk patients, there were no sex-related differences in terms of survival, HF hospitalization, functional status, and TR reduction up to 1 year. The IPTW analysis shows a survival benefit of TTVI over medical therapy alone in both women and men.

Fate of iatrogenic atrial septal defects following mitral transcatheter edge-to-edge repair - a subanalysis of the MITHRAS trial.

Persisting iatrogenic atrial septal defects (iASD) after transcatheter mitral edge-to-edge repair (M-TEER) are associated with impaired outcomes. We investigated the natural history of relevant iASDs with left-to-right shunting post-M-TEER, predictors of spontaneous closure of iASD between 1 and 6 months post-M-TEER, and outcomes (heart failure [HF] hospitalization) in patients with spontaneous closure versus those with persistent iASD 6 months post-M-TEER. Patients with a relevant iASD 1-month post-M-TEER, who were treated conservatively in the randomized controlled MITHRAS trial, underwent clinical follow-up including transesophageal echocardiography 6 months post-M-TEER. Overall, 36 patients (median 77 [interquartile range 65-81] years; 36% women) completed the 6-months follow-up. Six (17%) patients had a spontaneous closure of the iASD. The eccentricity index of the iASD 1-month after M-TEER was the strongest predictor for spontaneous closure (Odds ratio 3.78; 95% confidence interval 1.26-11.33, p = 0.01) and an eccentricity index of < 1.9 provided a sensitivity of 77% at a specificity of 83% for iASD persistence (Area under the curve 0.83, p < 0.001) within 6-months post M-TEER.At follow-up, a numerical difference in the endpoint of HF hospitalization between the spontaneous closure and the residual shunt group (0% vs. 20%, p = 0.25) was observed. The eccentricity of the iASD was the strongest predictor for spontaneous closure at 1-months and an eccentricity index of < 1.9 is associated with a high persistence rate for 6 month after M-TEER. Clinical Trial Registration ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03024268 Identifier: NCT03024268. a (red) is reflecting the mayor lengthwise dimension and b (blue) the mayor oblique dimension. The eccentricity index is calculated by dividing a through b. (Open circle) is depicting an example for a round iASD and (Open rhombus) an example for an eccentric iASD 1 month after M-TEER.

Sex-specific impact of anthropometric parameters on outcomes after transcatheter edge-to-edge repair for secondary mitral regurgitation.

BACKGROUND: Body surface area (BSA) has been reported to be the stronger predictor for prognosis than body mass index in heart failure (HF) patients. The sex-specific association of BSA with mortality has been unclear. METHODS: EuroSMR, a European multicenter registry, included patients who underwent edge-to-edge repair (TEER) for secondary mitral regurgitation (SMR). The outcome was two-year all-cause mortality. RESULTS: The present cohort included 1594 HF patients (age, 74 ± 10 years; male, 66%). Association of calculated BSA with two-year all-cause mortality was evaluated. Patients were classified into three BSA groups: the lowest 10% (S), the highest 10% (L), and intermediate between S and L (M). Mean BSA was 1.87 ± 0.21 m2 (male, 1.94 ± 0.18 m2; female, 1.73 ± 0.18 m2). The association of BSA with the endpoint in females showed a U-shaped curve, indicating worse prognosis for both S and L. The association in males followed a linear regression, demonstrating better prognosis for L. Hazard ratio (HR) of L to S in males was 0.43 (95% confidence interval [CI], 0.25-0.74; p = 0.002), whereas HR of L to M in females was 1.76 (95% CI, 1.11-2.78; p = 0.016) (p for interaction = 0.003). CONCLUSIONS: Sex-specific association patterns demonstrate the complex influence of anthropomorphic factors in HF patients scheduled for TEER. Further investigation beyond simple evaluation of weight and height is needed for better comprehension of the obesity paradox and better prediction of the results of transcatheter therapy in HF patients.

Right ventricular dysfunction predicts outcome after transcatheter mitral valve repair for primary mitral valve regurgitation.

AIMS: Right ventricular dysfunction (RVD), as expressed by right ventricular to pulmonary artery coupling, has recently been identified as a strong outcome predictor in patients undergoing mitral valve edge-to-edge repair (M-TEER) for secondary mitral regurgitation (MR). The aim of this study was to define RVD in patients undergoing M-TEER for primary MR (PMR) and to evaluate its impact on procedural MR reduction, symptomatic development and 2-year all-cause mortality. METHODS AND RESULTS: This multicentre study included patients undergoing M-TEER for symptomatic PMR at nine international centres. The study cohort was divided into a derivation (DC) and validation cohort (VC) for calculation and validation of the best discriminatory value for RVD. A total of 648 PMR patients were included in the study. DC and VC were comparable regarding procedural success and outcomes at follow-up. Sensitivity analysis identified RVD as an independent predictor for 2-year mortality in the DC (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.47-3.81, p < 0.001), which was confirmed in the VC (HR 2.06, 95% CI 1.36-3.13, p < 0.001). Procedural success (MR ≤2+) and symptomatic improvement at follow-up (New York Heart Association [NYHA] class ≤II) were lower in PMR patients with RVD (MR ≤2+: 82% vs. 93%, p = 0.002; NYHA class ≤II: 57.3% vs. 66.5%, p = 0.09 for with vs. without RVD). In all PMR patients, the presence of RVD significantly impaired 2-year survival after M-TEER (HR 2.23, 95% CI 1.63-3.05, p < 0.001). CONCLUSIONS: Mitral valve edge-to-edge repair is an effective treatment option for PMR patients. The presence of RVD is associated with less MR reduction, less symptomatic improvement and increased 2-year mortality. Accordingly, RVD might be included into pre-procedural prognostic considerations.

Atrial Functional Tricuspid Regurgitation: Novel Definition and Impact on Prognosis.

BACKGROUND: Atrial functional tricuspid regurgitation (atrial TR) has received growing recognition as a TR entity with a distinct cause owing to its independence from valvular tethering as the predominant mechanism underlying TR. However, characterization of atrial TR varies, and a universal definition is lacking. METHODS: In total, 651 patients with significant functional TR were analyzed, including 438 conservatively treated individuals and 213 patients who received transcatheter tricuspid valve repair (TTVR). Based on a clustering approach, we defined atrial TR as tricuspid valve (TV) tenting height ≤10 mm, midventricular right ventricular diameter ≤38 mm, and left ventricular ejection fraction ≥50%. RESULTS: Patients with atrial TR were more often females, had higher right ventricular fractional area change, higher left ventricular ejection fraction, and lower LV end-diastolic diameter, TV tenting area and height, lower right ventricular and tricuspid annular size, enlarged, but lower right atrial area and lower TV effective regurgitant orifice area (all P<0.05). Patients with atrial TR had significantly better long-term survival than non-atrial TR in the conservatively treated TR cohort (P<0.01, n=438). Atrial TR was independently associated with a lower rate of the combined end point of mortality and heart failure hospitalization at 1-year follow-up in the TTVR cohort (hazard ratio, 0.39; P<0.05, n=213). TR degree was significantly reduced after TTVR in non-atrial and atrial TR (P<0.01). Functional parameters significantly improved following TTVR independent of TR cause (P<0.05). CONCLUSIONS: An echocardiography-based atrial TR definition is associated with prognostic relevance in patients with functional TR in conservatively treated TR and after TTVR.

Guideline-directed medical therapy in patients undergoing transcatheter edge-to-edge repair for secondary mitral regurgitation.

AIMS: Guideline-directed medical therapy (GDMT), based on the combination of beta-blockers (BB), renin-angiotensin system inhibitors (RASI), and mineralocorticoid receptor antagonists (MRA), is known to have a major impact on the outcome of patients with heart failure with reduced ejection fraction (HFrEF). Although GDMT is recommended prior to mitral valve transcatheter edge-to-edge repair (M-TEER), not all patients tolerate it. We studied the association of GDMT prescription with survival in HFrEF patients undergoing M-TEER for secondary mitral regurgitation (SMR). METHODS AND RESULTS: EuroSMR, a European multicentre registry, included SMR patients with left ventricular ejection fraction <50%. The outcome was 2-year all-cause mortality. Of 1344 patients, BB, RASI, and MRA were prescribed in 1169 (87%), 1012 (75%), and 765 (57%) patients at the time of M-TEER, respectively. Triple GDMT prescription was associated with a lower 2-year all-cause mortality compared to non-triple GDMT (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.60-0.91). The association persisted in patients with glomerular filtration rate <30 ml/min, ischaemic aetiology, or right ventricular dysfunction. Further, a positive impact of triple GDMT prescription on survival was observed in patients with residual mitral regurgitation of ≥2+ (HR 0.62; 95% CI 0.44-0.86), but not in patients with residual mitral regurgitation of ≤1+ (HR 0.83; 95% CI 0.64-1.08). CONCLUSION: Triple GDMT prescription is associated with higher 2-year survival after M-TEER in HFrEF patients with SMR. This association was consistent also in patients with major comorbidities or non-optimal results after M-TEER.

Transcatheter Mitral Valve Repair in Patients With Atrial Functional Mitral Regurgitation.

BACKGROUND: Among patients with severe functional mitral regurgitation (FMR), atrial functional mitral regurgitation (aFMR) represents an underrecognized entity. Data regarding outcomes after mitral valve transcatheter edge-to-edge repair (M-TEER) in aFMR remain scarce. OBJECTIVES: The objective of this study was to analyze the outcome of aFMR patients undergoing M-TEER. METHODS: Using patients from the international EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) registry undergoing M-TEER for FMR, the authors analyzed baseline characteristics and 2-year outcomes in aFMR in comparison to non-aFMR and ventricular FMR. Additionally, the impact of right ventricular dysfunction (RVD) (defined as right ventricular to pulmonary artery uncoupling) on outcome after M-TEER was assessed. RESULTS: Among 1,608 FMR patients treated by M-TEER, 126 (7.8%) were categorized as aFMR. All 126 aFMR patients had preserved left ventricular function without regional wall motion abnormalities, left arterial dilatation and Carpentier leaflet motion type I. Procedural success (defined as mitral regurgitation ≤2+ at discharge) was 87.2% (P < 0.001) and New York Heart Association (NYHA) functional class significantly improved during follow-up (NYHA functional class III/IV: 86.5% at baseline to 36.6% at follow-up; P < 0.001). The estimated 2-year survival rate in aFMR patients was 70.4%. Two-year survival did not differ significantly between aFMR, non-aFMR, and ventricular FMR. Besides NYHA functional class IV, RVD was identified as a strong independent predictor for 2-year survival (HR: 2.82 [95% CI: 1.24-6.45]; P = 0.014). CONCLUSIONS: aFMR is a frequent cause of FMR and can be effectively treated with M-TEER to improve symptoms at follow-up. Advanced heart failure symptoms and RVD were identified as important risk factors for survival in aFMR patients.