Percutaneous repair of moderate-to-severe or severe functional mitral regurgitation in patients with symptomatic heart failure: Baseline characteristics of patients in the RESHAPE-HF2 trial and comparison to COAPT and MITRA-FR trials.

The RESHAPE-HF2 trial is designed to assess the efficacy and safety of the MitraClip device system for the treatment of clinically important functional mitral regurgitation (FMR) in patients with heart failure (HF). This report describes the baseline characteristics of patients enrolled in the RESHAPE-HF2 trial compared to those enrolled in the COAPT and MITRA-FR trials. The RESHAPE-HF2 study is an investigator-initiated, prospective, randomized, multicentre trial including patients with symptomatic HF, a left ventricular ejection fraction (LVEF) between 20% and 50% with moderate-to-severe or severe FMR, for whom isolated mitral valve surgery was not recommended. Patients were randomized 1:1 to a strategy of delivering or withholding MitraClip. Of 506 patients randomized, the mean age of the patients was 70 ± 10 years, and 99 of them (20%) were women. The median EuroSCORE II was 5.3 (2.8-9.0) and median plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 2745 (1407-5385) pg/ml. Most patients were prescribed beta-blockers (96%), diuretics (96%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (82%) and mineralocorticoid receptor antagonists (82%). The use of sodium-glucose cotransporter 2 inhibitors was rare (7%). Cardiac resynchronization therapy (CRT) devices had been previously implanted in 29% of patients. Mean LVEF, left ventricular end-diastolic volume and effective regurgitant orifice area (EROA) were 31 ± 8%, 211 ± 76 ml and 0.25 ± 0.08 cm2, respectively, whereas 44% of patients had mitral regurgitation severity of grade 4+. Compared to patients enrolled in COAPT and MITRA-FR, those enrolled in RESHAPE-HF2 were less likely to have mitral regurgitation grade 4+ and, on average, HAD lower EROA, and plasma NT-proBNP and higher estimated glomerular filtration rate, but otherwise had similar age, comorbidities, CRT therapy and LVEF. Patients enrolled in RESHAPE-HF2 represent a third distinct population where MitraClip was tested in, that is one mainly comprising of patients with moderate-to-severe FMR instead of only severe FMR, as enrolled in the COAPT and MITRA-FR trials. The results of RESHAPE-HF2 will provide crucial insights regarding broader application of the transcatheter edge-to-edge repair procedure in clinical practice.

Anker SD ，Friede T ，von Bardeleben RS ，Butler J ，Khan MS ，Diek M ，Heinrich J ，Geyer M ，Placzek M ，Ferrari R ，Abraham WT ，Alfieri O ，Auricchio A ，Bayes-Genis A ，Cleland JGF ，Filippatos G ，Gustafsson F ，Haverkamp W ，Kelm M ，Kuck KH ，Landmesser U ，Maggioni AP ，Metra M ，Ninios V ，Petrie MC ，Rassaf T ，Ruschitzka F ，Schäfer U ，Schulze PC ，Spargias K ，Vahanian A ，Zamorano JL ，Zeiher A ，Karakas M ，Koehler F ，Lainscak M ，Öner A ，Mezilis N ，Theofilogiannakos EK ，Ninios I ，Chrissoheris M ，Kourkoveli P ，Papadopoulos K ，Smolka G ，Wojakowski W ，Reczuch K ，Pinto FJ ，Zmudka K ，Kalarus Z ，Adamo M ，Santiago-Vacas E ，Ruf TF ，Gross M ，Tongers J ，Hasenfuß G ，Schillinger W ，Ponikowski P ... -  《-》

Association of Effective Regurgitation Orifice Area to Left Ventricular End-Diastolic Volume Ratio With Transcatheter Mitral Valve Repair Outcomes: A Secondary Analysis of the COAPT Trial.

Lindenfeld J ，Abraham WT ，Grayburn PA ，Kar S ，Asch FM ，Lim DS ，Nie H ，Singhal P ，Sundareswaran KS ，Weissman NJ ，Mack MJ ，Stone GW ，Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) Investigators ... -  《-》

Treatment of functional mitral regurgitation in chronic heart failure: can we get a 'proof of concept' from the MITRA-FR and COAPT trials?

Functional mitral regurgitation (FMR) is associated with poor outcomes in patients with heart failure (HF). However, it is not clear whether FMR is just a consequence of left ventricular (LV) remodelling or a factor contributing to cardiomyopathy progression. There will be more clarity about this controversy when the effects of FMR correction on outcomes will be shown. FMR correction can be performed surgically or, more often, percutaneously with the MitraClip procedure. MitraClip is the most widely used device with more than 70 000 implants performed to date. Observational studies suggest that MitraClip treatment of FMR is safe and associated with improved symptoms, quality of life and functional status in HF patients. Two recently randomized controlled clinical trials have investigated the impact of MitraClip on the outcomes of HF patients: Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation (MITRA-FR) and Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT). Both trials randomized patients to MitraClip plus guideline-directed medical therapy (GDMT) or GDMT alone. No reduction in the primary endpoint of all-cause mortality or HF hospitalizations was shown in MITRA-FR, whereas a significant reduction in HF hospitalizations (primary endpoint) as well as in mortality alone were shown in COAPT. The aim of this review is to summarize the pathophysiology, prevalence, prognostic role and management of FMR, focusing on the differences between MITRA-FR and COAPT and trying to provide possible explanations for the diverging results. We speculate that the two trials should be interpreted as complementary rather than opposite. Patients with severe FMR (effective regurgitant orifice area > 30 mm2 ) despite maximum tolerated GDMT (including cardiac resynchronization therapy), and without too advanced cardiomyopathy seem to be the best candidates for MitraClip treatment. MITRA-FR and COAPT provide us a long awaited 'proof of concept': FMR may be considered a leading actor in cardiomyopathy progression rather than a mere marker of severity.

Senni M ，Adamo M ，Metra M ，Alfieri O ，Vahanian A ... -  《-》

Randomized investigation of the MitraClip device in heart failure: Design and rationale of the RESHAPE-HF2 trial design.

The safety and effectiveness of the MitraClip device to treat functional mitral regurgitation (FMR) has been tested in previous clinical trials yielding somewhat heterogeneous results in heart failure (HF) patients. Over time, the MitraClip device system has been modified and clinical practice evolved to consider also less severely diseased HF patients with FMR for this therapeutic option. The RESHAPE-HF2 trial aims to assess the safety and effectiveness of the MitraClip device system on top of medical therapy considered optimal in the treatment of clinically significant FMR in symptomatic patients with chronic HF. The RESHAPE-HF2 is an investigator-initiated, prospective, randomized, parallel-controlled, multicentre trial designed to evaluate the use of the MitraClip device (used in the most up-to-date version as available at sites) plus optimal standard of care therapy (device group) compared to optimal standard of care therapy alone (control group). Eligible subjects have signs and symptoms of HF (New York Heart Association [NYHA] class II-IV despite optimal therapy), and have moderate-to-severe or severe FMR, as confirmed by a central echocardiography core laboratory; have an ejection fraction between ≥20% and ≤50% (initially 15-35% for NYHA class II patients, and 15-45% for NYHA class III/IV patients); have been adequately treated per applicable standards, and have received appropriate revascularization and cardiac resynchronization therapy, if eligible; had a HF hospitalization or elevated natriuretic peptides (B-type natriuretic peptide [BNP] ≥300 pg/ml or N-terminal proBNP ≥1000 pg/ml) in the last 90 days; and in whom isolated mitral valve surgery is not a recommended treatment option. The trial has three primary endpoints, which are these: (i) the composite rate of total (first and recurrent) HF hospitalizations and cardiovascular death during 24 months of follow-up, (ii) the rate of total (i.e. first and recurrent) HF hospitalizations within 24 months, and (iii) the change from baseline to 12 months in the Kansas City Cardiomyopathy Questionnaire overall score. The three primary endpoints will be analysed using the Hochberg procedure to control the familywise type I error rate across the three hypotheses. The RESHAPE-HF2 trial will provide sound evidence on the MitraClip device and its effects in HF patients with FMR. The recruitment was recently completed with 506 randomized patients.

Anker SD ，Friede T ，von Bardeleben RS ，Butler J ，Fatima K ，Diek M ，Heinrich J ，Hasenfuß G ，Schillinger W ，Ponikowski P ... -  《-》

An Appraisal of the Association of Clinical Outcomes With the Severity of Regurgitant Volume Relative to End-Diastolic Volume in Patients With Secondary Mitral Regurgitation.

Gaasch WH ，Aurigemma GP ，Meyer TE 《-》