Burden of Heart Failure in Patients With Tricuspid Regurgitation and Effect of Transcatheter Repair on Different Subdimensions of Quality of Life.

BACKGROUND: Right-sided heart failure (HF) due to severe tricuspid regurgitation (TR) is associated with reduced quality of life (QoL). Here, we analyzed the impact of TR on specific QoL dimensions and the effect of transcatheter tricuspid valve intervention (TTVI) on individual QoL items. METHODS AND RESULTS: In this study, we included 174 patients with HF (49% women; median age, 79 years; 97% New York Heart Association ≥3) with baseline QoL assessment undergoing TTVI by transcatheter edge-to-edge-repair at our center between April 2016 and March 2022. QoL was assessed by the standardized Minnesota Living With HF Questionnaire. QoL change after TTVI and correlation to functional end points were analyzed. In addition, all QoL domains and the 21 individual items of the Minnesota Living With HF Questionnaire were analyzed. TTVI significantly reduced TR (TR ≥3: baseline 95%, 1-year-follow-up 7%; P<0.001). Total Minnesota Living with HF Questionnaire score improved from 37 (interquartile range, 26-50) points to 31 (interquartile range, 17-42) points (median follow-up-interval, 355 days; P<0.001). QoL improvement was associated with positive New York Heart Association class, 6-minute walking distance, and actigraphy changes (all P<0.05). The detailed analysis revealed that all items of the physical-related QoL dimension were impaired at baseline and strongly improved after TTVI. In contrast, the emotional and "social" Minnesota Living With HF Questionnaire dimensions were largely unaffected at baseline, yet specific items improved with TTVI. CONCLUSIONS: In this single-center study, we delineate the QoL-associated disease burden of TR and identify specific QoL items that improved after TTVI. Our findings support TTVI in patients with reduced QoL and may add to the development of specific tools assessing the functional status of an increasing patient population undergoing TTVI.

4-Year Follow-Up After Transcatheter Tricuspid Valve Replacement Using the EVOQUE System.

Transcatheter tricuspid valve replacement (TTVR) is an increasingly used treatment technique for patients with severe tricuspid regurgitation (TR). Currently, available data from international registries and randomized controlled trials provide outcome data until a maximum follow-up of 2 years after the procedure. This case report presents 4-year follow-up data for an 84-year-old woman who underwent TTVR for torrential TR in 2019. The patient experienced durable TR reduction, symptomatic improvement, right ventricular reverse remodeling, and substantial improvement in liver and kidney function.

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.

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.

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.

Immune-mediated denervation of the pineal gland underlies sleep disturbance in cardiac disease.

Disruption of the physiologic sleep-wake cycle and low melatonin levels frequently accompany cardiac disease, yet the underlying mechanism has remained enigmatic. Immunostaining of sympathetic axons in optically cleared pineal glands from humans and mice with cardiac disease revealed their substantial denervation compared with controls. Spatial, single-cell, nuclear, and bulk RNA sequencing traced this defect back to the superior cervical ganglia (SCG), which responded to cardiac disease with accumulation of inflammatory macrophages, fibrosis, and the selective loss of pineal gland-innervating neurons. Depletion of macrophages in the SCG prevented disease-associated denervation of the pineal gland and restored physiological melatonin secretion. Our data identify the mechanism by which diurnal rhythmicity in cardiac disease is disturbed and suggest a target for therapeutic intervention.

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.

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.

Longitudinal In Vivo Monitoring of Atheroprogression in Hypercholesterolemic Mice Using Photoacoustic Imaging.

BACKGROUND AND AIM: The ability to recognize and monitor atherosclerotic lesion development using noninvasive imaging is crucial in preventive cardiology. The aim of the present study was to establish a protocol for longitudinal monitoring of plaque lipid, collagen, and macrophage burden as well as of endothelial permeability. METHODS AND RESULTS: Photoacoustic signals derived from endogenous or exogenous dyes assessed in vivo, in plaques of albino Apoe -/- mice, correlated with lesion characteristics obtained after histomorphometric and immunofluorescence analyses, thus supporting the validity of our protocol. Using models of atheroprogression and regression, we could apply our imaging protocol to the longitudinal observation of atherosclerotic lesion characteristics in mice. CONCLUSIONS: The present study shows an innovative approach to assess arterial inflammation in a non-invasive fashion, applicable to longitudinal analyses of changes of atherosclerotic lesion composition. Such approach could prove important in the preclinical testing of therapeutic interventions in mice carrying pre-established lesions.

Transcatheter edge-to-edge mitral valve repair in mitral regurgitation: current status and future prospects.

INTRODUCTION: Mitral regurgitation (MR) is associated with substantial morbidity and mortality. Within the past 15 years, mitral valve edge-to-edge repair (M-TEER) has developed from an experimental approach to a guideline-recommended, safe, and effective treatment option for patients with severe primary or secondary mitral regurgitation. AREAS COVERED: This review covered relevant publications of M-TEER and summarizes the development of M-TEER devices within the last 15 years. It outlines anatomical challenges which drove the evolution of M-TEER devices, provides an overview about the current state of clinical application and research, and offers an outlook into the future of transcatheter mitral valve treatment. EXPERT OPINION: The development and refinement of new M-TEER device generations offer the possibility to treat a wide range of mitral valve anatomies. Choosing the best device for the individual anatomic properties of the patients and considering comorbidities is the key to maximized MR reduction, minimalized complication rates, and thus optimized postinterventional prognosis. Independent from prognostic implications, quality of life has become an important patient-centered outcome that can be improved by M-TEER in virtually all patients treated.

Secondary prevention in diabetic and nondiabetic coronary heart disease patients: Insights from the German subset of the hospital arm of the EUROASPIRE IV and V surveys.

BACKGROUND: Patients with coronary heart disease (CHD) with and without diabetes mellitus have an increased risk of recurrent events requiring multifactorial secondary prevention of cardiovascular risk factors. We compared prevalences of cardiovascular risk factors and its determinants including lifestyle, pharmacotherapy and diabetes mellitus among patients with chronic CHD examined within the fourth and fifth EUROASPIRE surveys (EA-IV, 2012-13; and EA-V, 2016-17) in Germany. METHODS: The EA initiative iteratively conducts European-wide multicenter surveys investigating the quality of secondary prevention in chronic CHD patients aged 18 to 79 years. The data collection in Germany was performed during a comprehensive baseline visit at study centers in Würzburg (EA-IV, EA-V), Halle (EA-V), and Tübingen (EA-V). RESULTS: 384 EA-V participants (median age 69.0 years, 81.3% male) and 536 EA-IV participants (median age 68.7 years, 82.3% male) were examined. Comparing EA-IV and EA-V, no relevant differences in risk factor prevalence and lifestyle changes were observed with the exception of lower LDL cholesterol levels in EA-V. Prevalence of unrecognized diabetes was significantly lower in EA-V as compared to EA-IV (11.8% vs. 19.6%) while the proportion of prediabetes was similarly high in the remaining population (62.1% vs. 61.0%). CONCLUSION: Between 2012 and 2017, a modest decrease in LDL cholesterol levels was observed, while no differences in blood pressure control and body weight were apparent in chronic CHD patients in Germany. Although the prevalence of unrecognized diabetes decreased in the later study period, the proportion of normoglycemic patients was low. As pharmacotherapy appeared fairly well implemented, stronger efforts towards lifestyle interventions, mental health programs and cardiac rehabilitation might help to improve risk factor profiles in chronic CHD patients.

Heterotopic Transcatheter Tricuspid Valve Replacement in a Patient With Carcinoid Heart Disease.

Neuroendocrine tumors can lead to carcinoid heart disease with subsequent development of severe tricuspid regurgitation due to thickening and restriction of the tricuspid leaflets. We present a patient who underwent successful heterotopic transcatheter tricuspid valve replacement for torrential tricuspid regurgitation due to carcinoid heart disease. (Level of Difficulty: Intermediate.).