The Diagnosis and Treatment of Tricuspid Regurgitation.

BACKGROUND: It is estimated that 6% of persons over age 75 have clinically relevant tricuspid regurgitation (TR). This condition carries a high mortality and is of particular interest because of the recent development of new interventional treatments. METHODS: This review is based on publications that were retrieved by a selective search in the PubMed database for randomized controlled trials (RCTs), observational studies, registry studies, expert recommendations, and current international guidelines. RESULTS: The evidence reveals that TR is an independent cause of mortality. Mortality is correlated with the severity of TR: approximately 35% of patients with severe TR and right heart failure die within 1 year, and about 60% within 3 years. The clinical course varies depending on the etiology (primary TR, atrial/ventricular secondary TR, association with pacemaker systems). In the outpatient setting, timely diagnosis by transthoracic echocardiography is crucial. The options for pharmacotherapy are essentially limited to diuretic treatment (grade 2a recommendation). Early referral to a specialized heart valve center is essential for the prevention of irreversible damage of the right heart and secondary end-organ damage, including cardiohepatic and cardiorenal syndromes. In the heart valve center, an extended diagnostic evaluation with multimodal imaging is followed by a case discussion by the interdisciplinary cardiac team, with individual evaluation of the treatment options. The first randomized controlled trial of treatment for TR yielded a win ratio of 1.48 (95% confidence interval, [1.06; 2.13]) for interventional treatment (edge-to-edge repair) compared to optimal medical therapy. CONCLUSION: As the understanding of tricuspid regurgitation improves, strategies for its interventional treatment are undergoing steady development, with the aim of lowering the mortality of this condition.

Residual tricuspid regurgitation after tricuspid transcatheter edge-to-edge repair: Insights into the EuroTR registry.

AIMS: Data on the prognostic impact of residual tricuspid regurgitation (TR) after tricuspid transcatheter edge-to-edge repair (T-TEER) are scarce. The aim of this analysis was to evaluate 2-year survival and symptomatic outcomes of patients in relation to residual TR after T-TEER. METHODS AND RESULTS: Using the large European Registry of Transcatheter Repair for Tricuspid Regurgitation (EuroTR registry) we investigated the impact of residual TR on 2-year all-cause mortality and New York Heart Association (NYHA) functional class at follow-up. The study further identified predictors for residual TR ≥3+ using a logistic regression model. The study included a total of 1286 T-TEER patients (mean age 78.0 ± 8.9 years, 53.6% female). TR was successfully reduced to ≤1+ in 42.4%, 2+ in 40.0% and 3+ in 14.9% of patients at discharge, while 2.8% remained with TR ≥4+ after the procedure. Residual TR ≥3+ was an independent multivariable predictor of 2-year all-cause mortality (hazard ratio 2.06, 95% confidence interval 1.30-3.26, p = 0.002). The prevalence of residual TR ≥3+ was four times higher in patients with higher baseline TR (vena contracta >11.1 mm) and more severe tricuspid valve tenting (tenting area >1.92 cm2). Of note, no survival difference was observed in patients with residual TR ≤1+ versus 2+ (76.2% vs. 73.1%, p = 0.461). The rate of NYHA functional class ≥III at follow-up was significantly higher in patients with residual TR ≥3+ (52.4% vs. 40.5%, p < 0.001). Of note, the degree of TR reduction significantly correlated with the extent of symptomatic improvement (p = 0.012). CONCLUSIONS: T-TEER effectively reduced TR severity in the majority of patients. While residual TR ≥3+ was associated with worse outcomes, no differences were observed for residual TR 1+ versus 2+. Symptomatic improvement correlated with the degree of TR reduction.

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.

[Clinical aspects and treatment of tricuspid valve regurgitation]. / Klinik und Therapie der Trikuspidalklappeninsuffizienz.

Tricuspid regurgitation (TR) leading to right heart failure is prevalent and associated with increased mortality. The significant under-recognition of the disease resulted from insufficient medical therapies and the high associated risk of surgical therapy. Over the last decade there has been a rapid development of interventional treatment options so that the disease has increasingly become the focus of attention of specialists in internal medicine and interventional cardiologists. The etiology of TR is differentiated into primary TR, secondary atrial TR, secondary ventricular TR and TR associated with cardiac implantable electronic devices (CIED). The TR was identified as an independent predictor of mortality, independent of associated diseases such as atrial fibrillation, left-sided heart failure or pulmonary hypertension. Even patients with low to moderate TR have a significantly increased risk of mortality. Early diagnostics and estimation of the severity by echocardiography as well as timely referral to a tertiary heart valve center are decisive in order to evaluate possible treatment options before irreversible right ventricular damage and secondary organ dysfunction occur. For transcatheter edge-to-edge repair and transcatheter tricuspid valve replacement there is now first evidence from randomized controlled studies. While the understanding of TR is continuously improving, new tricuspid valve repair and replacement systems are in a state of steady progress. Whether the treatment has an effect on reduction of the mortality and stabilization of right ventricular failure with a reduction in hospitalization, will first be shown in future studies.

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.

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.

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.

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.

Impact of Transcatheter Edge-to-Edge Mitral Valve Repair on Guideline-Directed Medical Therapy Uptitration.

BACKGROUND: Guideline-directed medical therapy (GDMT) optimization is mandatory before transcatheter edge-to-edge mitral valve repair (M-TEER) in patients with secondary mitral regurgitation (SMR) and heart failure (HF) with reduced ejection fraction (HFrEF). However, the effect of M-TEER on GDMT is unknown. OBJECTIVES: The authors sought to evaluate frequency, prognostic implications and predictors of GDMT uptitration after M-TEER in patients with SMR and HFrEF. METHODS: This is a retrospective analysis of prospectively collected data from the EuroSMR Registry. The primary events were all-cause death and the composite of all-cause death or HF hospitalization. RESULTS: Among the 1,641 EuroSMR patients, 810 had full datasets regarding GDMT and were included in this study. GDMT uptitration occurred in 307 patients (38%) after M-TEER. Proportion of patients receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists was 78%, 89%, and 62% before M-TEER and 84%, 91%, and 66% 6 months after M-TEER (all P < 0.001). Patients with GDMT uptitration had a lower risk of all-cause death (adjusted HR: 0.62; 95% CI: 0.41-0.93; P = 0.020) and of all-cause death or HF hospitalization (adjusted HR: 0.54; 95% CI: 0.38-0.76; P < 0.001) compared with those without. Degree of MR reduction between baseline and 6-month follow-up was an independent predictor of GDMT uptitration after M-TEER (adjusted OR: 1.71; 95% CI: 1.08-2.71; P = 0.022). CONCLUSIONS: GDMT uptitration after M-TEER occurred in a considerable proportion of patients with SMR and HFrEF and is independently associated with lower rates for mortality and HF hospitalizations. A greater decrease in MR was associated with increased likelihood for GDMT uptitration.

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.

Cardio-hepatic syndrome in patients undergoing mitral valve transcatheter edge-to-edge repair.

AIMS: The impact of the cardio-hepatic syndrome (CHS) on outcomes in patients undergoing mitral valve transcatheter edge-to-edge repair (M-TEER) for relevant mitral regurgitation (MR) is unknown. The objectives of this study were three-fold: (i) to characterize the pattern of hepatic impairment, (ii) to investigate the prognostic value of CHS, and (iii) to evaluate the changes in hepatic function after M-TEER. METHODS AND RESULTS: Hepatic impairment was quantified by laboratory parameters of liver function. In accordance with existing literature, two types of CHS were distinguished: ischaemic type I CHS (elevation of both transaminases) and cholestatic type II CHS (elevation of two out of three parameters of hepatic cholestasis). The impact of CHS on 2-year mortality was evaluated using a Cox model. The change in hepatic function after M-TEER was assessed by laboratory testing at follow-up. We analysed 1083 patients who underwent M-TEER for relevant primary or secondary MR at four European centres between 2008 and 2019. Ischaemic type I and cholestatic type II CHS were observed in 11.1% and 23.0% of patients, respectively. Predictors for 2-year all-cause mortality differed by MR aetiology. While in primary MR cholestatic type II CHS was independently associated with 2-year mortality, ischaemic CHS type I was an independent mortality predictor in secondary MR patients. At follow-up, patients with MR reduction ≤2+ (obtained in 90.7% of patients) presented with improved parameters of hepatic function (median reduction of 0.2 mg/dl, 0.2 U/L and 21 U/L for bilirubin, alanine aminotransferase and gamma-glutamyl transferase, respectively, p < 0.01). CONCLUSIONS: The CHS is frequently observed in patients undergoing M-TEER and significantly impairs 2-year survival. Successful M-TEER may have beneficial effects on CHS.

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.

Indocyanine green clearance predicts outcome in patients undergoing transcatheter valve intervention for severe atrio-ventricular valve regurgitation.

OBJECTIVES: Severe mitral regurgitation (MR) and tricuspid regurgitation (TR) aggravate haemodynamic stress leading to congestive heart failure with impaired hepatic function, also known as cardiohepatic syndrome (CHS). Current perioperative risk calculators do not sufficiently consider CHS and serum liver function parameters lack sensitivity to diagnose CHS. Indocyanine green and its elimination (measured by the LIMON® test) represent a dynamic and non-invasive test which correlates with the hepatic function. Nevertheless, its utility in the setting of transcatheter valve repair/replacement (TVR) to predict CHS and outcome remains unknown. METHODS: We analysed liver function and outcomes of patients undergoing TVR for MR or TR between August 2020 and May 2021 at the Munich University Hospital. RESULTS: Out of a total of 44 patients treated at the University Hospital of Munich, 21 (48%) were treated for severe MR, 20 (46%) for severe TR and 3 (7%) for both diseases. Procedural success defined as MR/TR ≤2+ was 94% among MR patients and 92% among TR patients. While classical serum liver function parameters did not change after TVR, there was a significant improvement in liver function as assessed by the LIMON® test (P ≤ 0.001). Patients with baseline indocyanine green plasma disappearance rate <12.95%/min showed significantly increased 1-year mortality (hazard ratio: 1.54, 95% confidence interval: 1.05-2.25, P = 0.027) and lower New York Hear Association class improvement (P = 0.05). CONCLUSIONS: Especially in the context of the recently stressed importance of a careful patient selection prior to the interdisciplinary treatment of valvular heart disease, the LIMON® test may provide further real-time information on the patients' cardiohepatic injury and prognosis.

Quantification of physical activity with prospective activity tracking after transfemoral aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a well-established, safe and effective therapy for severe symptomatic aortic stenosis (AS). The aim of this study was to objectively quantify improvement of physical activity after TAVR, with consideration of different low-gradient AS subtypes. METHODS AND RESULTS: All patients undergoing TAVR for severe AS were screened. Participants received a wearable activity tracker (Fitbit®) at hospital discharge following TAVR and 6 months thereafter. The difference of median daily steps was defined as surrogate outcome for physical activity. For analysis, patients were grouped into high-gradient (HG) AS (dPmean ≥40 mmHg), classical low-flow low-gradient (LFLG) AS (dPmean <40 mmHg, EF <50%), paradoxical LFLG-AS (dPmean <40 mmHg, EF ≥50%, SVi ≤35 ml/m2) and normal-flow low-gradient (NFLG) AS (dPmean <40 mmHg, EF ≥50%, SVi >35 ml/m2) according to mean transvalvular pressure gradient (dPmean), stroke volume index (SVi) and left-ventricular ejection fraction (LVEF). RESULTS AND CONCLUSIONS: The analysis is based on 230 patients. The median daily step count was 4409 [IQR 2581-7487] after hospital discharge and 5326 [IQR 3045-8668] 6 months thereafter. Median difference of daily steps was ∆529 [IQR -702-2152]). Patients with HG-AS and paradoxical LFLG-AS showed a significant improvement of daily steps (∆951 [IQR -378-2323], p <0.001 and (∆1392 [IQR -609-4444], p = 0.02, respectively). Patients with classical LFLG-AS showed no statistically relevant improvement of daily steps (∆192 [IQR -687-770], p = 0.79). Patients with NFLG-AS showed a numerical decline in daily steps without statistical significance (∆-300 [IQR -1334-1406], p = 0.67). This first prospective study of this sample size shows significant improvement of physical activity after TAVR with an objective and reproducible method. This was mainly driven by an improvement in patients with HG-AS and paradoxical LFLG-AS.