Right ventricular to pulmonary artery coupling in patients with different types of aortic stenosis undergoing TAVI.

BACKGROUND: Right ventricular (RV) dysfunction in patients undergoing transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) has long been disregarded. We aimed to assess the predictive value of RV to pulmonary artery coupling (RV/PAc), defined as tricuspid annular plane systolic excursion to systolic pulmonary artery pressure, on mortality in different flow types of AS after TAVI. METHODS: All patients undergoing TAVI for AS at our centre between 2018 and 2020 were assessed; 862 patients were analysed. The cohort was dichotomized using a ROC analysis (cut-off 0.512 mm/mmHg), into 429 patients with preserved and 433 patients with reduced RV/PAc. RESULTS: Reduced RV/PAc was associated with male sex and a higher rate of comorbidities. Short-term VARC-3 endpoints and NYHA classes at follow-up were comparable. Reduced RV/PAc was associated with higher 2-year all-cause mortality (35.0% [30.3-39.3%] vs. 15.4% [11.9-18.7%], hazard ratio 2.5 [1.9-3.4], p < 0.001). Cardiovascular mortality was almost tripled. Results were consistent after statistical adjustment and in a multivariate model. Sub-analyses of AS flow types revealed lower RV/PAc in classical and paradoxical low-flow low-gradient AS, with the majority having reduced RV/PAc (74% and 59%). RV/PAc retained its predictive value in these subgroups. CONCLUSIONS: RV dysfunction defined by low RV/PAc is a strong mortality predictor after TAVI independent of flow group. It should be incorporated in future TAVI risk assessment.

Congestion patterns in severe tricuspid regurgitation and transcatheter treatment: Insights from a multicentre registry.

AIMS: While invasively determined congestion holds mechanistic and prognostic significance in acute heart failure (HF), its role in patients with tricuspid regurgitation (TR)-related right- heart failure (HF) undergoing transcatheter tricuspid valve intervention (TTVI) is less well established. A comprehensive understanding of congestion patterns might aid in procedural planning, risk stratification, and the identification of patients who may benefit from adjunctive therapies before undergoing TTVI. The aim of this study was to investigate the role of congestion patterns in patients with severe TR and its implications for TTVI. METHODS AND RESULTS: Within a multicentre, international TTVI registry, 813 patients underwent right heart catheterization (RHC) prior to TTVI and were followed up to 24 months. The median age was 80 (interquartile range 76-83) years and 54% were women. Both mean right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) were associated with 2-year mortality on Cox regression analyses with Youden index-derived cut-offs of 17 mmHg and 19 mmHg, respectively (p < 0.01 for all). However, RAP emerged as an independent predictor of outcomes following multivariable adjustments. Pre-interventionally, 42% of patients were classified as euvolaemic (RAP <17 mmHg, PCWP <19 mmHg), 23% as having left-sided congestion (RAP <17 mmHg, PCWP ≥19 mmHg), 8% as right-sided congestion (RAP ≥17 mmHg, PCWP <19 mmHg), and 27% as bilateral congestion (RAP ≥17 mmHg, PCWP ≥19 mmHg). Patients with right-sided or bilateral congestion had the lowest procedural success rates and shortest survival times. Congestion patterns allowed for discerning specific patient's physiology and specifying prognostic implications of right ventricular to pulmonary artery coupling surrogates. CONCLUSION: In this large cohort of invasively characterized patients undergoing TTVI, congestion patterns involving right-sided congestion were associated with low procedural success and higher mortality rates after TTVI. Whether pre-interventional reduction of right-sided congestion can improve outcomes after TTVI should be established in dedicated studies.

Paradox of disproportionate atrial functional mitral regurgitation and survival after transcatheter edge-to-edge repair.

AIMS: This study aims to assess the applicability of the mitral regurgitation (MR) proportionality concept in patients with atrial functional mitral regurgitation (aFMR) treated with transcatheter edge-to-edge repair (M-TEER). We hypothesized that patients with disproportionate MR (higher MR relative to left ventricular size) would exhibit different outcomes compared to those with proportionate MR, despite undergoing M-TEER. METHODS AND RESULTS: We retrospectively analysed 98 patients with aFMR from the EuroSMR registry who underwent M-TEER between 2008 and 2019. Patients met criteria for aFMR (normal indexed left ventricular end-diastolic volume [LVEDV], preserved left ventricular ejection fraction [LVEF] ≥ 50% without regional wall motion abnormalities, and structurally normal mitral valves). We excluded patients with missing effective regurgitant orifice area (EROA) or LVEDV data. The primary endpoint was 2-year mortality, with an EROA/LVEDV ratio employed to differentiate disproportionate from proportionate MR. Procedural success and baseline characteristics were analysed, and multivariate Cox proportional hazards models were used to identify mortality predictors. The mean patient age was 79 ± 7.3 years, with 68.8% female, and 79% had a history of atrial fibrillation. The mean EROA was 0.27 ± 0.14 cm2, and LVEDV was 95.6 ± 33.7 mL. Disproportionate MR was identified with an EROA/LVEDV ratio >0.339 cm2/100 mL. While procedural success was similar in both groups, disproportionate MR was associated with a numerically higher estimate of systolic pulmonary artery pressures (sPAP) and rates of NYHA ≥III and TR ≥ 3+. Disproportionate MR had a significant association with increased 2-year mortality (P < 0.001). The EROA/LVEDV ratio and tricuspid annular plane systolic excursion (TAPSE) were independent predictors of 2-year mortality (EROA/LVEDV: HR: 1.35, P = 0.010; TAPSE: HR: 0.85, P = 0.020). CONCLUSIONS: This analysis introduces the MR proportionality concept in aFMR patients and its potential prognostic value. Paradoxically, disproportionate MR in aFMR was linked to a 1.35-fold increase in 2-year mortality post-M-TEER, emphasizing the importance of accurate preprocedural FMR characterization. Our findings in patients with disproportionate MR indicate that a high degree of aFMR with high regurgitant volumes may lead to aggravated symptoms, which is a known contributor to increased mortality following M-TEER. These results underline the need for further research into the pathophysiology of aFMR to inform potential preventative and therapeutic strategies, ensuring optimal patient outcomes.

The Evolving Concept of Secondary Mitral Regurgitation Phenotypes: Lessons From the M-TEER Trials.

Conflicting results from 2 randomized clinical trials of transcatheter mitral valve edge-to-edge repair in secondary mitral regurgitation (SMR) have led to the recognition that SMR is a heterogeneous disease entity presenting with different functional and morphological phenotypes. This review summarizes the current knowledge on SMR caused primarily by atrial secondary mitral regurgitation (aSMR) and ventricular SMR pathology. Although aSMR is generally characterized by severe left atrial enlargement in the setting of preserved left ventricular anatomy and function, different patterns of mitral annular distortion cause different phenotypes of aSMR. In ventricular SMR, the relation of SMR severity to left ventricular dilation as well as the degree of pulmonary hypertension and right ventricular dysfunction are important phenotypic characteristics, which are key for a better understanding of prognosis and treatment response.

Ten Future Challenges in the Field of Transcatheter Mitral Valve Edge-to-Edge Repair.

Mitral valve transcatheter edge-to-edge repair (M-TEER) and replacement (TMVR) have evolved as guideline-recommended treatment approaches for mitral regurgitation (MR). Even though they are supported by a growing body of evidence from either randomized trials or large registries, there are still several unsolved challenges in the field of interventional MR treatment. In the present review, we discuss the ten most important open questions regarding M-TEER and TMVR.

Clinical Characteristics and Outcomes of Patients Screened for Transcatheter Tricuspid Valve Replacement: The TriACT Registry.

BACKGROUND: Transcatheter tricuspid valve replacement (TTVR) abolishes tricuspid regurgitation (TR) and has emerged as a definitive treatment for TR. OBJECTIVES: The purpose of this multicenter, observational study was to determine the clinical characteristics and short-term outcomes of patients with TR screened for TTVR. METHODS: Patients underwent TTVR screening at 7 centers on a compassionate-use basis. The primary endpoints were NYHA functional class and TR grade at 30-day follow-up. Secondary endpoints included all-cause mortality, heart failure hospitalization, technical success, and reasons for TTVR screening failure. RESULTS: A total of 149 patients (median age 79 years [Q1-Q3: 72-84 years], 54% women) underwent TTVR screening. The TTVR screening failure rate was 74%, mainly related to large tricuspid annular diameter. Patients undergoing TTVR (n = 38) had significant functional improvements (NYHA functional class I or II from 21% to 68%; P < 0.001), with TR ≤1+ in 97% at 30-day follow-up (P < 0.001 from baseline). Technical success was achieved in 91%, with no intraprocedural mortality or conversion to surgery. At 30-day follow-up, mortality was 8%, heart failure hospitalization 5%, major bleeding 18%, and reintervention 9%. Patients who failed screening for TTVR and subsequently underwent "bailout" transcatheter edge-to-edge repair (n = 26) had favorable outcomes (NYHA functional class I or II from 27% to 58%; P < 0.001), with TR ≤1+ in 43% at 30-day follow-up (P < 0.001 from baseline). CONCLUSIONS: This first real-world report of TTVR screening demonstrated a high screening failure rate, mainly related to large tricuspid annular diameter. Patients undergoing TTVR had superior TR reduction and symptom alleviation compared with bailout tricuspid transcatheter edge-to-edge repair, at the cost of greater procedural complications.

Guideline-directed medical therapy assessment in heart failure patients undergoing percutaneous mitral valve repair.

AIMS: Achieving optimized guideline-directed medical therapy (GDMT) is recommended prior to transcatheter mitral valve edge-to-edge repair (M-TEER) for secondary mitral regurgitation (SMR). We aimed to propose and validate an easy-to-use score for assessing the quality of GDMT in patients with heart failure with reduced ejection fraction (HFrEF) undergoing M-TEER. METHODS AND RESULTS: Among the 1641 EuroSMR patients enrolled in the EuroSMR Registry who underwent M-TEER, a total of 1072 patients [median age 74, interquartile range (IQR) 67-79 years, 29% female] had complete data on GDMT and a left ventricular ejection fraction ≤ 40% and were included in the current study. We proposed a GDMT score that considers the dosage levels of three medication classes (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists), with a maximum score of 12 points indicating optimal GDMT. The primary outcome was all-cause mortality. The median GDMT score was 4 points (IQR 3-6). All three domains of the scoring system were associated with all-cause mortality (P < 0.05 for all). The overall GDMT score was associated with all-cause mortality (hazard ratio 0.90, 95% confidence interval 0.86-0.95 for each 1-point increase in the GDMT score). This association remained significant after adjusting for renal function and co-morbidities. CONCLUSIONS: This study demonstrates the utility of a simple GDMT scoring system for assessing the adequacy of GDMT in HFrEF patients with relevant SMR undergoing M-TEER. The GDMT score has potential applications in guiding the design of future clinical trials and aiding clinical decision-making processes.

Artificial intelligence-derived risk score for mortality in secondary mitral regurgitation treated by transcatheter edge-to-edge repair: the EuroSMR risk score.

BACKGROUND AND AIMS: Risk stratification for mitral valve transcatheter edge-to-edge repair (M-TEER) is paramount in the decision-making process to appropriately select patients with severe secondary mitral regurgitation (SMR). This study sought to develop and validate an artificial intelligence-derived risk score (EuroSMR score) to predict 1-year outcomes (survival or survival + clinical improvement) in patients with SMR undergoing M-TEER. METHODS: An artificial intelligence-derived risk score was developed from the EuroSMR cohort (4172 and 428 patients treated with M-TEER in the derivation and validation cohorts, respectively). The EuroSMR score was validated and compared with established risk models. RESULTS: The EuroSMR risk score, which is based on 18 clinical, echocardiographic, laboratory, and medication parameters, allowed for an improved discrimination of surviving and non-surviving patients (hazard ratio 4.3, 95% confidence interval 3.7-5.0; P < .001), and outperformed established risk scores in the validation cohort. Prediction for 1-year mortality (area under the curve: 0.789, 95% confidence interval 0.737-0.842) ranged from <5% to >70%, including the identification of an extreme-risk population (2.6% of the entire cohort), which had a very high probability for not surviving beyond 1 year (hazard ratio 6.5, 95% confidence interval 3.0-14; P < .001). The top 5% of patients with the highest EuroSMR risk scores showed event rates of 72.7% for mortality and 83.2% for mortality or lack of clinical improvement at 1-year follow-up. CONCLUSIONS: The EuroSMR risk score may allow for improved prognostication in heart failure patients with severe SMR, who are considered for a M-TEER procedure. The score is expected to facilitate the shared decision-making process with heart team members and patients.

Atrial Functional Tricuspid Regurgitation in Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: Knowledge about atrial functional tricuspid regurgitation (afTR) in transcatheter aortic valve replacement (TAVR) patients is scarce. OBJECTIVES: The aim of the study was to analyze the association between the entity and the development of tricuspid regurgitation (TR) in patients undergoing TAVR for aortic stenosis and concomitant TR. METHODS: We analyzed patients undergoing TAVR for severe aortic stenosis from January 2013 to December 2020 and concomitant at least moderate TR at baseline. afTR was defined as enlargement of the right atrium in relation to the right ventricle. TR development after TAVR and 3-year all-cause mortality were evaluated. RESULTS: Out of 3,474 TAVR patients, we identified 420 patients with concomitant at least moderate TR. A total of 363 patients were included in the study, with 178 patients stratified in the afTR and 185 in the non-afTR group based on a receiver-operating characteristic curve cutoff of 1.132 of the right atrial/right ventricular area ratio. TR improvement after TAVR was observed in significantly less patients with afTR compared with non-afTR (31.1% vs 60.6%; P < 0.001). Multivariate regression analysis confirmed afTR as independent predictor for TR persistence (adjusted OR: 2.80; 95% CI: 1.66-4.76; P < 0.001). Moreover, afTR was associated with aggravation of TR after TAVR (17.0% vs 6.8%; P = 0.013). Three-year all-cause mortality was significantly higher in patients with persistence compared with patients with improvement of TR (P < 0.001). CONCLUSIONS: In TAVR patients, afTR is an independent predictor for TR persistence. Moreover, TR persistence is associated with increased 3-year all-cause mortality.

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.

Applying the TRILUMINATE Eligibility Criteria to Real-World Patients Receiving Tricuspid Valve Transcatheter Edge-to-Edge Repair.

BACKGROUND: According to the TRILUMINATE (Clinical Trial to Evaluate Cardiovascular Outcomes in Patients Treated With the Tricuspid Valve Repair System) trial, transcatheter tricuspid edge-to-edge repair (T-TEER) improves quality of life beyond medical treatment, while no effects on heart failure hospitalization (HFH) and survival were observed at 1 year. However, the generalizability of the TRILUMINATE trial to real-world conditions remains a subject of discussion. OBJECTIVES: The aim of this study was to apply the clinical TRILUMINATE inclusion and exclusion criteria to a real-world T-TEER patient group and evaluate symptomatic and survival outcome in TRILUMINATE-eligible and TRILUMINATE-ineligible patients. METHODS: Clinical TRILUMINATE inclusion and exclusion criteria were applied to a cohort of patients who underwent T-TEER at 5 European centers from 2016 to 2022. Study patients were compared regarding baseline characteristics, survival, HFH, and symptomatic outcomes as measured by NYHA functional class, a quality-of-life questionnaire and 6-minute walk distance. RESULTS: Of 962 patients, 54.8% were classified as TRILUMINATE eligible, presenting with superior left ventricular function and fewer comorbidities compared with the ineligible population. Tricuspid regurgitation reduction, improvement in NYHA functional class, quality of life, and exercise capacity were comparable in both groups. However, the 1-year survival and HFH rates significantly differed (tricuspid regurgitation ≤2+ at discharge, 82% vs 85%; survival, 85% vs 75%; HFH, 14% vs 22% for eligible vs ineligible patients). CONCLUSIONS: The observed differences in survival and HFH outcomes suggest a limited generalizability of TRILUMINATE to real-world conditions and indicate the need for additional studies evaluating the outcomes after T-TEER in less selected patient populations.

[T-TEER: description of a development process]. / T-TEER: Beschreibung eines Entwicklungsprozesses.

Tricuspid valve regurgitation (TR) is becoming increasingly more clinically important. While considered as an accompanying symptom of left heart pathologies in the past, TR is now seen as an independent and clinically significant condition. TR can lead to volume overload of the right ventricle, resulting in dilatation of the tricuspid valve annulus and worsening of the regurgitation. Undetected or untreated severe TR can lead to recurrent cardiac decompensation with hospitalization, reduced quality of life and death. Previous treatment options were limited to cardiac surgery and associated with high complication and mortality rates, especially in isolated TR. Therefore, many patients are considered inoperable so that the new interventional treatment measures nowadays often represent the only treatment option. Interventional treatment options such as the edge-to-edge procedure (T-TEER) with TriClip™ or the PASCAL™ system are very safe interventions that have already shown promising results, including reduction of TR, improvement in heart failure symptoms and the quality of life. The influence on the mortality and the necessity for hospitalization due to heart failure are currently being investigated in several randomized studies. Patient selection and timing of the intervention are crucial. Cardiovascular imaging plays a decisive role in selecting the appropriate method and timing of the intervention. The prognosis depends on factors, such as the severity of TR, right ventricular dysfunction, and pulmonary arterial hypertension. Overall, interventional TR treatment is a promising advancement in treatment from which many patients can benefit in the future.

Cardio-hepatic syndrome in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Cardiohepatic syndrome (CHS) has been identified as an important but underrecognized survival predictor in multiple cardiovascular disease entities. The objectives of this study were to evaluate the prevalence and prognostic value of CHS in patients undergoing TAVR for severe aortic stenosis (AS). METHODS: The study included patients with available laboratory parameters of hepatic function who underwent TAVR from July 2013 until December 2019 at our center. CHS was defined as an elevation of at least two of three laboratory cholestasis parameters above the upper limit of normal (bilirubin, alkaline phosphatase, and gamma glutamyl transferase). Study endpoints were three-year survival, technical and device failure (VARC 3), as well as New York Heart Association (NYHA) functional class at follow-up. RESULTS: Among a total of 953 analyzed patients (47.6% females, median age 80.0 [76.0-85.0] years) CHS was present in 212 patients (22.4%). In patients with vs. without CHS, rates of technical (6.1% vs. 8.4%, p = 0.29) and device failure (18.9% vs. 17.3%, p = 0.59) were comparable. NYHA functional class at baseline and follow-up was more severe in patients with CHS. Nevertheless, heart failure symptoms improved from baseline to follow-up irrespective of hepatic function. Three-year survival rates were significantly lower in patients with CHS (49.4 vs. 65.4%, p < 0.001). The predictive value of CHS persisted after adjustment in a multivariable analysis (hazard ratio 1.58, p < 0.01). CONCLUSION: In patients undergoing TAVR, CHS is prevalent in 22% of patients and is associated with increased postinterventional mortality. Thus, CHS should be included in the decision-making process within the TAVR heart team. Cardiohepatic syndrome (CHS) as defined by an elevation of at least two of three laboratory cholestasis parameters above the upper limit of normal was prevalent in 22% of patients undergoing TAVR for severe AS. The presence of CHS was associated with more severe heart failure symptoms and worse three-year survival.

Impact of mitral regurgitation aetiology on the outcomes of transcatheter aortic valve implantation.

BACKGROUND: Concomitant moderate/severe mitral regurgitation (MR) is observed in 17-35% of patients undergoing transcatheter aortic valve implantation (TAVI) and contributes to a worse prognosis. Studies analysing outcomes in patients undergoing TAVI with different MR aetiologies, including atrial functional MR (aFMR), are lacking. AIMS: We aimed to analyse outcomes and changes in MR severity in patients with aFMR, ventricular functional (vFMR) and primary mitral regurgitation (PMR) following TAVI. METHODS: We analysed all consecutive patients with at least moderate MR undergoing TAVI between January 2013 and December 2020 at the Munich University Hospital. Characterisation of MR aetiology was performed by detailed individual echocardiographic assessment. Three-year mortality, changes in MR severity and New York Heart Association (NYHA) Functional Class at follow-up were assessed. RESULTS: Out of 3,474 patients undergoing TAVI, 631 patients showed MR ≥2+ (172 with aFMR, 296 with vFMR, 163 with PMR). Procedural characteristics and endpoints were comparable between groups. The rate of MR improvement was 80.2% in aFMR patients, which was significantly higher compared to both other groups (vFMR: 69.4%; p=0.03; PMR: 40.8%; p<0.001). The estimated 3-year survival rates did not differ between aetiologies (p=0.57). However, MR persistence at follow-up was associated with increased mortality (hazard ratio 1.49, 95% confidence interval: 1.04-2.11; p=0.027), mainly driven by the PMR subgroup of patients. NYHA Class improved significantly in all groups. In patients with baseline MR ≥3+, the PMR aetiology was associated with the lowest MR improvement, the lowest survival rates and least symptomatic improvement. CONCLUSIONS: TAVI reduces MR severity and symptoms in patients with aFMR, vFMR and less-pronounced PMR. The presence of aFMR was associated with the greatest MR severity improvement.