Clinical outcomes through 12 months in patients with degenerative mitral regurgitation treated with the MitraClip® device in the ACCESS-EUrope Phase I trial†

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Impact of asymmetric tethering on outcomes after edge-to-edge mitral valve repair for secondary mitral regurgitation

BACKGROUND The impact of postero-anterior and medio-lateral mitral valve (MV) tethering patterns on outcomes in patients undergoing transcatheter edge-to-edge repair (M-TEER) for secondary mitral regurgitation (SMR) is unknown. METHODS The ratio of the posterior to anterior MV leaflet angle (PLA/ALA) in MV segment 2 was defined as postero-anterior tethering asymmetry. Medio-lateral tethering asymmetry was assessed as the ratio of the medial (segment 3) to lateral (segment 1) MV tenting area. We used receiver-operating characteristics and a Cox regression model to identify cut-off values of asymmetric anteroposterior and medio-lateral tethering for prediction of 2~year all-cause mortality after TMVR. RESULTS Among 178 SMR patients, postero-anterior tethering was asymmetric in 67 patients (37.9%, PLA/ALA ratio > 1.54). Asymmetric medio-lateral tethering (tenting area ratio > 1.49) was observed in 49 patients (27.5%). M-TEER reduced MR to ≤ 2 + in 92.1% of patients; MR reduction was less effective in the presence of asymmetric postero-anterior tethering (p = 0.02). A multivariable Cox regression model identified both types of asymmetric MV tethering to be associated with increased all-cause 2-year mortality (postero-anterior tethering asymmetry: HR = 2.77, CI 1.43-5.38; medio-lateral tethering asymmetry: HR = 2.90, CI 1.54-5.45; p < 0.01). CONCLUSIONS Asymmetric postero-anterior and medio-lateral MV tethering patterns are associated with increased 2-year mortality in patients undergoing M-TEER for SMR. A detailed echocardiographic analysis of MV anatomy may help to identify patients who profit most from M-TEER

Ex Vivo Assessment of Coronary Atherosclerotic Plaque by Grating-Based Phase-Contrast Computed Tomography Correlation With Optical Coherence Tomography

Objectives: The aim of this study was to determine the diagnostic accuracy of grating-based phase-contrast computed tomography (gb-PCCT) to classify and quantify coronary vessel characteristics in comparison with optical coherence tomography (OCT) and histopathology in an ex vivo setting. Materials and Methods: After excision from 5 heart specimens, 15 human coronary arteries underwent gb-PCCT examination using an experimental imaging setup consisting of a rotating molybdenum anode x-ray tube, a Talbot-Lau grating interferometer, and a single photon counting detector. Subsequently, all vessels were imaged by OCT and histopathologically processed. Optical coherence tomography, gb-PCCT, and histopathology images were manually matched using anatomical landmarks. Optical coherence tomography and gb-PCCT were reviewed by 2 independent observers blinded to histopathology. Vessel, lumen, and plaque area were measured, and plaque characteristics (lipid rich, calcified, and fibrous) were determined for each section. Measures of diagnostic accuracy were derived, applying histopathology as the standard of reference. Results: Of a total of 286 assessed cross sections, 241 corresponding sections were included in the statistical analysis. Quantitative measures derived from gb-PCCT were significantly higher than from OCT (P = 0.85 for gb-PCCT and >= 0.61 for OCT, respectively). Results of Bland-Altman analysis demonstrated smaller mean differences between OCT and histopathology than for gb-PCCT and histopathology. Limits of agreement were narrower for gb-PCCT with regard to lumen area, for OCT with regard to plaque area, and were comparable with regard to vessel area. Based on histopathology, 228/241 (94.6%) sections were classified as fibrous, calcified, or lipid rich. The diagnostic accuracy of gb-PCCT was excellent for the detection of all plaque components (sensitivity, >= 0.95;specificity, >= 0.94), whereas the results for OCT showed sensitivities of >= 0.73 and specificities of >= 0.66. Conclusions: In this ex vivo setting, gb-PCCT provides excellent results in the assessment of coronary atherosclerotic plaque characteristics and vessel dimensions in comparison to OCT and histopathology. Thus, the technique may serve as adjunct nondestructive modality for advanced plaque characterization in an experimental setting

Right ventricular function in transcatheter mitral and tricuspid valve edge-to-edge repair

Since transcatheter edge-to-edge repair (TEER) has become a valuable therapy in the treatment of both, mitral (MR) and tricuspid regurgitation (TR), the question of optimized patient selection has gained growing importance. After years of attributing rather little attention to the right ventricle (RV) and its function in the setting of valvular heart failure, this neglect has recently changed. The present review sought to summarize anatomy and function of the RV in a clinical context and aimed at presenting the current knowledge on how the RV influences outcomes after TEER for atrioventricular regurgitation. The anatomy of the RV is determined by its unique shape, which necessitates to use three-dimensional imaging methods for detailed and comprehensive characterization. Complex parameters such as RV to pulmonary artery coupling (RVPAc) have been developed to combine information of RV function and afterload which is primary determined by the pulmonary vasculature and LV filling pressure. Beyond that, TR, which is closely related to RV function also plays an important role in the setting of TEER. While mitral valve transcatheter edge-to-edge repair (M-TEER) leads to reduction of concomitant TR in some patients, the prognostic value of TR in the setting of M-TEER remains unclear. Overall, this review summarizes the current state of knowledge of the outstanding role of RV function and associated TR in the setting of TEER and outlines the unsolved questions associated with right-sided heart failure

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

Concomitant percutaneous coronary intervention in patients undergoing transcatheter aortic valve implantation

Background Patients undergoing transcatheter aortic valve implantation (TAVI) frequently have coronary artery disease requiring percutaneous coronary intervention (PCI). Usually, PCI and TAVI are performed in two separate procedures and current studies are investigating potential benefits regarding the order. However, the two interventions may also be performed simultaneously, thereby limiting the risk associated with repeated vascular access. Data evaluating benefit and harm of concomitant procedures are scarce. Aims Therefore, this study aimed to evaluate concomitant PCI (coPCI) in TAVI patients regarding Valve Academic Research Consortium 3 (VARC-3) endpoints and long-term mortality. Methods A total of 2233 consecutive TAVI patients from the EVERY-VALVE registry were analyzed according to the VARC-3 endpoint definitions. A total of 274 patients had undergone TAVI and concomitant PCI (coPCI group). They were compared to 226 TAVI patients who had received PCI within 60 days before TAVI in a stepwise approach (swPCI group) and to the remaining 1733 TAVI patients who had not undergone PCI recently (noPCI group). Results Overall median age was 81.4 years, median Society of Thoracic Surgeons score was 4.0%. Patients in the coPCI and in the swPCI group were predominantly male with reduced left-ventricular ejection fraction. Rates of VARC-3 composite endpoints technical success and 30-day device success were comparable between all three groups. Mortality rates at 3 years after TAVI were similar (coPCI, 34.2% vs. swPCI, 31.9% vs. noPCI, 34.0% p = 0.84). Conclusions coPCI during TAVI seems comparable in a retrospective analysis. Compared to a stepwise approach, it has similar rates of composite endpoints technical success and device success as well as long-term mortality

Biodegradable Polymer Versus Permanent Polymer Drug-Eluting Stents and Everolimus- Versus Sirolimus-Eluting Stents in Patients With Coronary Artery Disease 3-Year Outcomes From a Randomized Clinical Trial

ObjectivesThe aim of this study was to compare the 3-year efficacy and safety of biodegradable polymer with permanent polymer stents and of everolimus-eluting stents (EES) with sirolimus-eluting stents (SES).BackgroundBiodegradable polymer drug-eluting stents (DES) offer potential for enhanced late outcomes in comparison with permanent polymer stents. In addition, there is increasing interest in the comparison of EES (Xience, Abbott Vascular, Abbott Park, Illinois) versus SES (Cypher, Cordis Corporation, Miami Lakes, Florida).MethodsThe ISAR-TEST 4 (Intracoronary Stenting and Angiographic Results: Test Efficacy of 3 Limus-Eluting Stents-4) was a randomized clinical trial with broad inclusion criteria, enrolling 2,603 patients at 2 clinics in Munich, Germany. Patients were randomized to either biodegradable polymer (n = 1,299) or permanent polymer stents (n = 1,304); patients treated with permanent polymer stents were randomly allocated to EES (n = 652) or SES (n = 652). The primary endpoint was the composite of cardiac death, target vessel-related myocardial infarction, or target lesion revascularization.ResultsClinical events continued to accrue at a low rate out to 3 years in all groups. Overall, there was no significant difference between biodegradable polymer and permanent polymer DES with regard to the primary endpoint (20.1% vs. 20.9%, hazard ratio [HR]: 0.95, 95% confidence interval [CI]: 0.80 to 1.13; p = 0.59). Rates of definite/probable stent thrombosis were also similar in both groups (1.2% vs. 1.7%, respectively; HR: 0.71, 95% CI: 0.37 to 1.39; p = 0.32). In patients treated with permanent polymer stents, EES were comparable to SES with regard to the primary endpoint (19.6% vs. 22.2%, respectively; HR: 0.87, 95% CI: 0.68 to 1.11; p = 0.26) as well as definite/probable stent thrombosis (1.4% vs. 1.9%, HR: 0.75, 95% CI: 0.32 to 1.78; p = 0.51).ConclusionsBiodegradable polymer and permanent polymer DES are associated with similar clinical outcomes at 3 years. In addition, EES are comparable to SES in terms of overall clinical efficacy and safety. (Intracoronary Stenting and Angiographic Results: Test Efficacy of 3 Limus-Eluting STents [ISAR-TEST 4]: Prospective, Randomized Trial of 3-limus Agent-eluting Stents With Different Polymer Coatings; NCT00598676

Cardiac output states in patients with severe functional tricuspid regurgitation: impact on treatment success and prognosis

Aims To investigate whether there is evidence for distinct cardiac output (CO) based phenotypes in patients with chronic right heart failure associated with severe tricuspid regurgitation (TR) and to characterize their impact on TR treatment and outcome. Methods and results A total of 132 patients underwent isolated transcatheter tricuspid valve repair (TTVR) for functional TR at two centres. Patients were clustered according to k-means clustering into low [cardiac index (CI)  2.6 L/min/m2) clusters. All-cause mortality and clinical characteristics during follow-up were compared among different CO clusters. Mortality rates were highest for patients in a low (24%) and high CO state (42%, log-rank P < 0.001). High CO state patients were characterized by larger inferior vena cava diameters (P = 0.003), reduced liver function, higher incidence of ascites (P = 0.006) and markedly reduced systemic vascular resistance (P < 0.001) as compared to TTVR patients in other CO states. Despite comparable procedural success rates, the extent of changes in right atrial pressures (P = 0.01) and right ventricular dimensions (P < 0.001) per decrease in regurgitant volume following TTVR was less pronounced in high CO state patients as compared to other CO states. Successful TTVR was associated with the smallest prognostic benefit among low and high CO state patients. Conclusions Patients with chronic right heart failure and severe TR display distinct CO states. The high CO state is characterized by advanced congestive hepatopathy, a substantial decrease in peripheral vascular tone, a lack of response of central venous pressures to TR reduction, and worse prognosis. These data are relevant to the pathophysiological understanding and management of this important clinical syndrome. Graphical Abstract Proposed mechanism of hypercirculatory tricuspid regurgitation. Tricuspid regurgitation related backward failure causes liver congestion and dysfunction with portal hypertension and reduced washout of vasoactive substances. Consequent splanchnic and peripheral vasodilatation alongside with reduced renal blood flow results in renin–angiotensin–aldosterone system (RAAS) activation and sympathetic overactivation. The sympathetic drive and volume retention lead to further capacitance depletion and volume overload, eventually resulting in a high cardiac output state, with limited preload reduction and prognostic benefit following transcatheter tricuspid valve repair. The alterations in the graph should be interpreted as simultaneous interaction rather than a timeline. Continuous lines indicate findings in the present study. Dashed lines express currently accepted mechanistical considerations. AP, alkaline phosphatase; γGT, gamma-glutamyl-transferase; RA, right atrium; RV, right ventricle

12-Month outcomes of transcatheter tricuspid valve repair with the PASCAL system for severe tricuspid regurgitation

Objectives We investigated the durability of tricuspid regurgitation (TR) reduction and the clinical outcomes through 12 months after transcatheter tricuspid valve repair (TTVr) with the PASCAL Transcatheter Valve Repair System. Background TTVr has rapidly developed and demonstrated favorable acute outcomes, but longer follow-up data are needed. Methods Overall, 30 patients (age 77 ± 6 years; 57% female) received PASCAL implantation from September 2017 to May 2019 and completed a clinical follow-up at 12 months. Results The TR etiology was functional in 25 patients (83%), degenerative in three (10%), and mixed in two (7%). All patients had TR severe or greater (massive or torrential in 80%) and heart failure symptoms (90% in NYHA III or IV) under optimal medical treatment. Single-leaflet device attachment occurred in two patients. Moderate or less TR was achieved in 23/28 patients (82%) at 30 days, which was sustained at 12 months (86%). Two patients underwent repeat TTVr due to residual torrential TR (day 173) and recurrence of severe TR (day 280), respectively. One-year survival rate was 93%; 6 patients required rehospitalization due to acute heart failure. NYHA functional class I or II was achieved in 90% and 6-minute walk distance improved from 275 ± 122 m at baseline to 347 ± 112 m at 12-month (+72 ± 82 m, p < .01). There was no stroke, endocarditis, or device embolization during the follow-up. Conclusions Twelve-month outcomes from this multicenter compassionate use experience with the PASCAL System demonstrated high procedural success, acceptable safety, and significant clinical improvement