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Aim: 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. Methods and results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Aims: Low serum albumin levels are associated with poor prognosis in numerous chronic disease states but the relationship between albumin and outcomes in patients with heart failure (HF) and secondary mitral regurgitation (SMR) has not been described. Methods and results: The randomized COAPT trial evaluated the safety and effectiveness of transcatheter edge‐to‐edge repair (TEER) with the MitraClipTM plus guideline‐directed medical therapy (GDMT) versus GDMT alone in patients with symptomatic HF and moderate‐to‐severe or severe SMR. Baseline serum albumin levels were measured at enrolment. Among 614 patients enrolled in COAPT, 559 (91.0%) had available baseline serum albumin levels (median 4.0 g/dl, interquartile range 3.7–4.2 g/dl). Patients with albumin <4.0 g/dl compared with ≥4.0 g/dl were older and more likely to have ischaemic cardiomyopathy and a hospitalization within the year prior to enrolment. After multivariable adjustment, patients with albumin <4.0 g/dl had higher 4‐year rates of all‐cause death (63.7% vs. 47.6%; adjusted hazard ratio 1.34, 95% confidence interval 1.02–1.74; p = 0.032), but there were no significant differences in HF hospitalizations (HFH) or all‐cause hospitalizations according to baseline serum albumin level. The relative effectiveness of TEER plus GDMT versus GDMT alone was consistent in patients with low and high albumin levels (pinteraction = 0.19 and 0.35 for death and HFH, respectively). Conclusion: Low baseline serum albumin levels were independently associated with reduced 4‐year survival in patients with HF and severe SMR enrolled in the COAPT trial, but not with HFH. Patients treated with TEER derived similarly robust reductions in both death and HFH regardless of baseline albumin level. [ABSTRACT FROM AUTHOR]

Aims The impact of mitral valve geometry on outcomes after MitraClip treatment in secondary mitral regurgitation (MR) has not been examined. We therefore sought to evaluate the association between mitral valve geometry and outcomes of patients with heart failure (HF) and secondary MR treated with guideline-directed medical therapy (GDMT) and MitraClip. Methods and results Mitral valve geometry was assessed from the baseline echocardiograms in 614 patients from the COAPT trial. The primary endpoint for the present study was the composite of all-cause mortality or HF hospitalization (HFH) within 2 years. Effect of treatment arm (MitraClip plus maximally tolerated GDMT vs. GDMT alone) on outcomes according to baseline variables was assessed. Among 29 baseline mitral valve echocardiographic parameters, increasing anteroposterior mitral annular diameter was the only independent predictor of the composite endpoint of all-cause mortality or HFH [adjusted hazard ratio (aHR) per cm 1.49; P = 0.04]. The effective regurgitant orifice area (EROA) was independently associated with all-cause mortality alone (aHR per cm2 2.97; P = 0.04) but not with HFH, whereas increasing anteroposterior mitral annular diameter was independently associated with HFH alone (aHR per cm 1.85; P = 0.005) but not all-cause mortality. Other mitral valve morphologic parameters were unrelated to outcomes. MitraClip reduced HFH and mortality independent of anteroposterior mitral annular diameter and EROA (P interaction = 0.77 and 0.27, respectively). Conclusion In patients with HF and severe secondary MR, a large anteroposterior mitral annular diameter and greater EROA were the strongest echocardiographic predictors of HFH and death in patients treated with GDMT alone and with the MitraClip. [ABSTRACT FROM AUTHOR]

Aims Baseline renal dysfunction (RD) adversely impacts outcomes among patients with heart failure (HF) and severe secondary mitral regurgitation (MR). Heart failure and MR, in turn, accelerate progression to end-stage renal disease (ESRD), worsening prognosis. We sought to determine the impact of RD in HF patients with severe MR and the impact of transcatheter mitral valve repair (TMVr) on new-onset ESRD and the need for renal replacement therapy (RRT). Methods and results The COAPT trial randomized 614 patients with HF and severe MR to MitraClip plus guideline-directed medical therapy (GDMT) vs. GDMT alone. Patients were stratified into three RD subgroups based on baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m2): none (≥60), moderate (30–60), and severe (<30). End-stage renal disease was defined as eGFR <15 mL/min/1.73 m2 or RRT. The 2-year rates of all-cause death or HF hospitalization (HFH), new-onset ESRD, and RRT according to RD and treatment were assessed. Baseline RD was present in 77.0% of patients, including 23.8% severe RD, 6.0% ESRD, and 5.2% RRT. Worse RD was associated with greater 2-year risk of death or HFH (none 45.3%; moderate 53.9%; severe 69.2%; P < 0.0001). MitraClip vs. GDMT alone improved outcomes regardless of RD (P interaction = 0.62) and reduced new-onset ESRD [2.9 vs. 8.1%, hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.15–0.76, P = 0.008] and the need for new RRT (2.5 vs. 7.4%, HR 0.33, 95% CI 0.14–0.78, P = 0.011). Conclusion Baseline RD was common in the HF patients with severe MR enrolled in COAPT and strongly predicted 2-year death and HFH. MitraClip treatment reduced new-onset ESRD and the need for RRT, contributing to the improved prognosis after TMVr. [ABSTRACT FROM AUTHOR]

Congest Heart Fail. The long-term impact of cardiac resynchronization therapy (CRT)-induced acute improvement in left ventricular (LV) function is largely unknown. The goal of this study was to evaluate the significance of acute improvement in LV function resulting from CRT in patients with chronic heart failure (HF). The authors compared 6-month clinical composite score (CCS) and LV end-systolic (ESV) reduction (≥15% from baseline) response rates of CRT-treated patients enrolled in the Predictors of Response to CRT (PROSPECT) trial who showed an acute increase (≥15% from baseline) in LV ejection fraction (EF) vs those who did not show a similar change in EF. Of the 396 patients who had pre-implant and post-implant EF measurements, 78 (19.7%) had an increase in EF and 318 (80.3%) did not. Acute reduction of mitral regurgitation by at least one grade occurred in 26% and 23% of patients with and without an acute increase in EF, respectively. Patients with an acute increase in EF had significantly lower baseline EF and smaller LV volumes but otherwise similar characteristics. At 6 months, LVEF and LV volumes were significantly higher and lower in the increased EF group, respectively; however, CCS improvement (70.5% vs 69.5%) and LVESV reduction (57.1% vs 54.9%) response rates were comparable in the two groups. An acute ≥15% increase in LVEF with CRT does not predict 6-month effects of CRT on patient outcomes or LV reverse remodeling. That such findings occur in patients with smaller LV volumes, however, may provide additional insight into the mechanisms responsible for CRT-induced long-term improvement in LV function and clinical benefit. [ABSTRACT FROM AUTHOR]

Background: In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, transcatheter mitral valve repair (TMVr) resulted in fewer heart failure hospitalizations (HFHs) and lower mortality at 24 months in patients with heart failure (HF) with mitral regurgitation (MR) secondary to left ventricular dysfunction compared with guideline-directed medical therapy (GDMT) alone.Objectives: This study determined if these benefits persisted to 36 months and if control subjects who were allowed to cross over at 24 months derived similar benefit.Methods: This study randomized 614 patients with HF with moderate-to-severe or severe secondary MR, who remained symptomatic despite maximally tolerated GDMT, to TMVr plus GDMT versus GDMT alone. The primary effectiveness endpoint was all HFHs through 24-month follow-up. Patients have now been followed for 36 months.Results: The annualized rates of HFHs per patient-year were 35.5% with TMVr and 68.8% with GDMT alone (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.37 to 0.63; p < 0.001; number needed to treat (NNT) = 3.0; 95% CI: 2.4 to 4.0). Mortality occurred in 42.8% of the device group versus 55.5% of control group (HR: 0.67; 95% CI: 0.52 to 0.85; p = 0.001; NNT = 7.9; 95% CI: 4.6 to 26.1). Patients who underwent TMVr also had sustained 3-year improvements in MR severity, quality-of-life measures, and functional capacity. Among 58 patients assigned to GDMT alone who crossed over and were treated with TMVr, the subsequent composite rate of mortality or HFH was reduced compared with those who continued on GDMT alone (adjusted HR: 0.43; 95% CI: 0.24 to 0.78; p = 0.006).Conclusions: Among patients with HF and moderate-to-severe or severe secondary MR who remained symptomatic despite GDMT, TMVr was safe, provided a durable reduction in MR, reduced the rate of HFH, and improved survival, quality of life, and functional capacity compared with GDMT alone through 36 months. Surviving patients who crossed over to device treatment had a prognosis comparable to those originally assigned to transcatheter therapy. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation [COAPT]; NCT01626079). [ABSTRACT FROM AUTHOR]

Although malnutrition is associated with poor prognosis in several diseases, its prognostic impact in patients with heart failure (HF) and secondary mitral regurgitation (SMR) is not understood. The purpose of this study was to assess the prevalence and impact of malnutrition in HF patients with severe SMR randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip plus guideline-directed medical therapy (GDMT) vs GDMT alone in the COAPT trial. Baseline malnutrition risk was calculated using the validated geriatric nutritional risk index (GNRI) score. Patients were categorized as having "malnutrition" (GNRI ≤98) vs "no malnutrition" (GNRI >98). Outcomes were assessed through 4 years. The primary endpoint of interest was all-cause mortality. Among 552 patients, median baseline GNRI was 109 (IQR: 101-116); 94 (17.0%) had malnutrition. All-cause mortality at 4 years was greater in patients with vs those without malnutrition (68.3% vs 52.8%; P = 0.001). Using multivariable analysis, both baseline malnutrition (adjusted-HR [adj-HR]: 1.37; 95% CI: 1.03-1.82; P = 0.03) and randomization to TEER plus GDMT compared with GDMT alone (adj-HR: 0.65; 95% CI: 0.51-0.82; P = 0.0003) were independent predictors of 4-year mortality. In contrast, GNRI was unrelated to the 4-year rate of heart failure hospitalization (HFH), although TEER treatment reduced HFH (adj-HR: 0.46; 95% CI: 0.36-0.56). The reductions in death (adj- P interaction = 0.46) and HFH (adj- P interaction = 0.67) with TEER were consistent in patients with and without malnutrition. Malnutrition was present in 1 of 6 patients with HF and severe SMR enrolled in COAPT and was independently associated with increased 4-year mortality (but not HFH). TEER reduced mortality and HFH in patients with and without malnutrition. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT]; NCT01626079) [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The impact of transcatheter edge-to-edge repair (TEER) on the rate and prognostic impact of hospitalizations in patients with heart failure (HF) and severe secondary mitral regurgitation is unknown.Objectives: This study sought to evaluate the effect of the MitraClip percutaneous edge-to edge repair system on fatal and nonfatal hospitalizations and their relationship with mortality in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial.Methods: Patients with HF (n = 614) with severe secondary mitral regurgitation were randomized to TEER plus guideline-directed medical therapy (GDMT) versus GDMT alone. Hospitalizations were classified as fatal if death occurred during that hospitalization or nonfatal if the patient was discharged alive.Results: At 2 years, TEER treatment, compared with GDMT alone, resulted in lower time-to-first-event rates of any heart failure hospitalization (HFH) (34.8% vs 56.4%; HR: 0.51; 95% CI: 0.39-0.66) and fatal HFH (6.5% vs 12.6%; HR: 0.47; 95% CI: 0.26-0.85). TEER also resulted in lower rates of all-cause nonfatal and fatal hospitalizations. During the 2-year follow-up period, patients who underwent TEER spent an average of 2 more months alive and out of the hospital than did patients treated with GDMT alone (581 ± 27 days vs 519 ± 26 days; P = 0.002). All HFHs (adjusted HR: 6.37; 95% CI: 4.63-8.78) and nonfatal HFHs (adjusted HR: 1.78; 95% CI: 1.27-2.49) were consistently independently associated with increased 2-year mortality in both the TEER and GDMT groups (Pinteraction = 0.34 and 0.39, respectively).Conclusions: In the COAPT trial, compared with GDMT alone, patients with HF and severe secondary mitral regurgitation undergoing TEER with the percutaneous edge-to edge repair system had lower 2-year rates of fatal and nonfatal all-cause hospitalizations and HFH and spent more time alive and out of the hospital. HFHs were strongly associated with mortality, irrespective of treatment. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT]; NCT01626079). [ABSTRACT FROM AUTHOR]

Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous etiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodeling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of transcatheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives. [ABSTRACT FROM AUTHOR]

Background: In the randomized COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation), among 614 patients with heart failure with 3+ or 4+ secondary mitral regurgitation (MR), transcatheter mitral valve repair (TMVr) with the MitraClip reduced MR, heart failure hospitalizations, and mortality and improved quality of life compared with guideline-directed medical therapy (GDMT) alone. We aimed to examine the prognostic relationship between MR reduction and outcomes after TMVr and GDMT alone.Methods: Outcomes in COAPT between 30 days and 2 years were examined on the basis of the severity of residual MR at 30 days.Results: TMVr-treated patients had less severe residual MR at 30 days than GDMT-treated patients (0/1+, 2+, and 3+/4+: 72.9%, 19.9%, and 7.2% versus 8.2%, 26.1%, and 65.8%, respectively [P<0.0001]). The rate of composite death or heart failure hospitalizations between 30 days and 2 years was lower in patients with 30-day residual MR of 0/1+ and 2+ compared with patients with 30-day residual MR of 3+/4+ (37.7% versus 49.5% versus 72.2%, respectively [P<0.0001]). This relationship was consistent in the TMVr and GDMT arms (Pinteraction=0.92). The improvement in Kansas City Cardiomyopathy Questionnaire score from baseline to 30 days was maintained between 30 days and 2 years in patients with 30-day MR ≤2+ but deteriorated in those with 30-day MR 3+/4+ (-0.3±1.7 versus -9.4±4.6 [P=0.0008]) consistently in both groups (Pinteraction=0.95).Conclusions: In the COAPT trial, reduced MR at 30 days was associated with greater freedom from death or heart failure hospitalizations and improved quality of life through 2-year follow-up whether the MR reduction was achieved by TMVr or GDMT. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension worsens prognosis in patients with heart failure (HF) and secondary mitral regurgitation (SMR).Objectives: This study sought to determine whether baseline pulmonary hypertension influences outcomes of transcatheter mitral valve repair (TMVr) in patients with HF with SMR.Methods: In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, 614 patients with HF with moderate-to-severe or severe SMR were randomized to TMVr with the MitraClip plus guideline-directed medical therapy (GDMT) (n = 302) versus GDMT alone (n = 312). Baseline pulmonary artery systolic pressure (PASP) estimated from echocardiography was categorized as substantially increased (≥50 mm Hg) versus not substantially increased (<50 mm Hg).Results: Among 528 patients, 184 (82 TMVr, 102 GDMT) had PASP of ≥50 mm Hg (mean: 59.1 ± 8.8 mm Hg) and 344 (171 TMVr, 173 GDMT) had PASP of <50 mm Hg (mean: 36.3 ± 8.1 mm Hg). Patients with PASP of ≥50 mm Hg had higher 2-year rates of death or HF hospitalization (HFH) compared to those with PASP of <50 mm Hg (68.8% vs. 49.1%; adjusted hazard ratio: 1.52; 95% confidence interval: 1.17 to 1.97; p = 0.002). Rates of death or HFH were reduced by TMVr versus GDMT alone, irrespective of baseline PASP (pinteraction = 0.45). TMVr reduced PASP from baseline to 30 days to a greater than GDMT alone (adjusted least squares mean: -4.0 vs. -0.9 mm Hg; p = 0.006), a change that was associated with reduced risk of death or HFH between 30 days and 2 years (adjusted hazard ratio: 0.91 per -5 mm Hg PASP; 95% confidence interval: 0.86 to 0.96; p = 0.0009).Conclusions: Elevated PASP is associated with a worse prognosis in patients with HF with severe SMR. TMVr with the MitraClip reduced 30-day PASP and 2-year rates of death or HFH compared with GDMT alone, irrespective of PASP. [ABSTRACT FROM AUTHOR]

Secondary (also known as functional) mitral regurgitation (MR) has increased substantially over the last several decades due to an increase in the prevalence of dilated cardiomyopathy (ischemic and non-ischemic). Mortality and morbidity in patients with dilated cardiomyopathy is much greater when associated with MR as compared to without MR. MR will result in further left ventricular (LV) volume overload, LV dilation, and pupillary muscle displacement resulting in deterioration of the severity of MR leading to a vicious cycle. Optimization of heart failure medical therapy, and cardiac resynchronization therapy for those that qualify, can improve severity of MR; however, significant MR will persist in certain patients. Transcatheter mitral valve repair to treat significant MR using the MitraClip (Abbott, Menlo Park, California), which grasps and coapts the posterior and anterior mitral valve leaflets, in appropriately selected patients with dilated cardiomyopathy and secondary MR has been shown to improve quality of life and prolong survival. [ABSTRACT FROM AUTHOR]

Background: The presence of tricuspid regurgitation (TR) may affect prognosis in patients with mitral regurgitation (MR).Objectives: This study sought to determine the impact of TR on outcomes in patients with heart failure and severe secondary MR randomized to guideline-directed medical therapy (GDMT) or edge-to-edge repair with the MitraClip in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial.Methods: A total of 614 patients with symptomatic heart failure with moderate to severe (3+) or severe (4+) secondary MR were randomized to maximally tolerated GDMT plus MitraClip or GDMT alone; 599 had core laboratory evaluable echocardiograms. Patients were divided into 2 groups by baseline TR severity: none/trace/mild TR (≤Mild TR) (n = 501 [83.6%]) and moderate/severe TR (≥Mod TR) (n = 98 [16.4%]). Two-year composite endpoints of death or heart failure hospitalization (HFH) and the individual endpoints were analyzed.Results: Patients with ≥Mod TR were more likely to be New York Heart Association functional class III/IV (p < 0.0001) and have a Society of Thoracic Surgeons score of ≥8 (p < 0.0001), anemia (p = 0.02), chronic kidney disease (p = 0.003), and higher N-terminal pro-B-type natriuretic peptide (p = 0.02) than those with ≤Mild TR. Patients with ≥Mod TR had more severe MR (p = 0.0005) despite smaller left ventricular volumes (p = 0.005) and higher right ventricular systolic pressure (p < 0.0001). At 2 years, the composite rate of death or HFH was higher in patients with ≥Mod TR compared with ≤Mild TR treated with GDMT alone (83.0% vs. 64.3%; hazard ratio: 1.74; 95% confidence interval: 1.24 to 2.45; p = 0.001) but not following MitraClip (48.2% vs. 44.0%; hazard ratio: 1.14; 95% confidence interval: 0.71 to 1.84; p = 0.59). Rates of death or HFH, as well as death and HFH alone, were reduced by MitraClip compared with GDMT, irrespective of baseline TR grade (pinteraction = 0.16, 0.29, and 0.21 respectively).Conclusions: Patients with severe secondary MR who also had ≥Mod TR had worse clinical and echocardiographic characteristics and worse clinical outcomes compared to those with ≤Mild TR. Within the COAPT trial, MitraClip improved outcomes in patients with and without ≥Mod TR severity compared with GDMT alone. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079). [ABSTRACT FROM AUTHOR]

Background: Transcatheter mitral valve repair with the MitraClip results in marked clinical improvement in some but not all patients with secondary mitral regurgitation (MR) and heart failure (HF).Objectives: This study sought to evaluate the clinical predictors of a major response to treatment in the COAPT trial.Methods: Patients with HF and severe MR who were symptomatic on maximally tolerated guideline-directed medical therapy (GDMT) were randomly assigned to MitraClip plus GDMT or GDMT alone. Super-responders were defined as those alive without HF hospitalization and with ≥20-point improvement in the Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS) score at 12 months. Responders were defined as those alive without HF hospitalization and with a 5 to <20-point KCCQ-OS improvement at 12 months. Nonresponders were those who either died, were hospitalized for HF, or had <5-point improvement in KCCQ-OS at 12 months.Results: Among 614 enrolled patients, 41 (6.7%) had missing KCCQ-OS data and could not be classified. At 12 months, there were 79 super-responders (27.2%), 55 responders (19.0%), and 156 nonresponders (53.8%) in the MitraClip arm compared with 29 super-responders (10.2%), 46 responders (16.3%), and 208 nonresponders (73.5%) in the GDMT-alone arm (overall p < 0.0001). Independent baseline predictors of clinical responder status were lower serum creatinine and KCCQ-OS scores and treatment assignment to MitraClip. MR grade and estimated right ventricular systolic pressure at 30 days were improved to a greater degree in super-responders and responders but not in nonresponders.Conclusions: Baseline predictors of clinical super-responders in patients with HF and severe secondary MR in the COAPT trial were lower serum creatinine, KCCQ-OS score and MitraClip treatment. Improved MR severity and reduced right ventricular systolic pressure at 30 days are associated with a long-term favorable clinical response after transcatheter mitral valve repair. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079). [ABSTRACT FROM AUTHOR]

Background: In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, transcatheter mitral valve repair (TMVr) with the MitraClip rapidly improved health status and reduced the long-term risks for death and heart failure (HF) hospitalization in patients with HF and severe secondary mitral regurgitation who remained symptomatic despite maximally tolerated guideline-directed medical therapy (GDMT).Objectives: The aim of this study was to examine if early health status changes were associated with long-term clinical outcomes in the COAPT population.Methods: The association between change in health status (Kansas City Cardiomyopathy Questionnaire overall summary score [KCCQ-OS]) from baseline to 1 month and the composite rate of death or HF hospitalization between 1 month and 2 years in the COAPT trial were evaluated, and whether treatment (TMVr or GDMT alone) modified this association was tested.Results: Among 551 patients with HF and severe secondary mitral regurgitation who were alive at 1 month, those randomized to TMVr were more likely than those randomized to GDMT alone to achieve a ≥10-point improvement in KCCQ-OS from baseline to 1 month (TMVr, 58%; GDMT alone, 26%). Early improvement in KCCQ-OS was inversely associated with the risk for death or HF hospitalization between 1 month and 2 years (p < 0.001). When analyzed as a continuous variable, a 10-point increase in KCCQ-OS was associated with a 14% lower risk for death or HF hospitalization (hazard ratio: 0.86; 95% confidence interval: 0.81 to 0.92; p < 0.001), with no significant interaction with treatment group (pinteraction = 0.17). After adjusting for demographic and clinical factors, the association between change in KCCQ-OS and outcomes was strengthened (hazard ratio: 0.79; 95% confidence interval: 0.73 to 0.86; p < 0.001).Conclusions: In patients with HF and severe secondary mitral regurgitation, a short-term change in disease-specific health status was strongly associated with the subsequent long-term risk for death or HF hospitalization. These findings reinforce the prognostic utility of serial KCCQ-OS assessments to identify patients at risk for poor long-term clinical outcomes in this population. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial]; NCT01626079). [ABSTRACT FROM AUTHOR]

Background: In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial among patients with heart failure (HF) and moderate-to-severe (3+) or severe (4+) secondary mitral regurgitation, patients treated with transcatheter mitral valve repair (TMVr) through leaflet approximation had reduced rates of HF hospitalization and mortality compared with guideline-directed medical therapy (GDMT) alone.Objectives: The purpose of this study was to describe the echocardiographic patient qualification process for the COAPT trial, baseline echocardiographic characteristics, changes over time, and the interaction between treatment group and echocardiographic parameters on clinical outcomes.Methods: A novel echocardiographic algorithm was implemented for grading mitral regurgitation severity during the screening process. Standardized echocardiograms were obtained at baseline and during regular follow-up intervals through 2 years, and were analyzed by a core laboratory.Results: A total of 614 patients were randomized to TMVr plus maximally tolerated GDMT or GDMT alone. Mean baseline left ventricular (LV) ejection fraction was 31.3 ± 9.3%, LV end-diastolic volume was 192.7 ± 71 ml, and effective regurgitant orifice area was 0.41 ± 0.15 cm2. The beneficial effect of TMVr compared with GDMT alone was consistent in all echocardiographic subgroups, independent of the severity of LV dysfunction, LV dilatation, pulmonary hypertension, severity of tricuspid regurgitation, or individual mitral regurgitation characteristics. The LV ejection fraction decreased and the LV volumes progressively increased in both groups during follow-up, although less after TMVr (p < 0.05).Conclusions: HF patients in the COAPT trial with 3+ or 4+ secondary mitral regurgitation, selected using strict echocardiographic criteria, benefitted from TMVr with reduced 2-year rates of death and HF hospitalization. Strict application of these echocardiographic criteria should enable the COAPT results to be translated to clinical practice. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] [COAPT]; NCT01626079). [ABSTRACT FROM AUTHOR]

Background: The COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) demonstrated that edge-to-edge transcatheter mitral valve repair (TMVr) with the MitraClip resulted in reduced mortality and heart failure hospitalizations and improved quality of life compared with maximally tolerated guideline-directed medical therapy (GDMT) in patients with heart failure and 3 to 4+ secondary mitral regurgitation. Whether TMVr is cost-effective compared with GDMT in this population is unknown.Methods: We used data from the COAPT trial to perform a formal patient-level economic analysis of TMVr+GDMT versus GDMT alone for patients with heart failure and 3 to 4+ secondary mitral regurgitation from the perspective of the US healthcare system. Costs for the index TMVr hospitalization were assessed using a combination of resource-based accounting and hospital billing data (when available). Follow-up medical care costs were estimated on the basis of medical resource use collected during the COAPT trial. Health utilities were estimated for all patients at baseline and 1, 6, 12, and 24 months with the Short Form Six-Dimension Health Survey.Results: Initial costs for the TMVr procedure and index hospitalization were $35 755 and $48 198, respectively. Although follow-up costs were significantly lower with TMVr compared with GDMT ($26 654 versus $38 345; P=0.018), cumulative 2-year costs remained higher with TMVr because of the upfront cost of the index procedure ($73 416 versus $38 345; P<0.001). When in-trial survival, health utilities, and costs were modeled over a lifetime horizon, TMVr was projected to increase life expectancy by 1.13 years and quality-adjusted life-years by 0.82 years at a cost of $45 648, yielding a lifetime incremental cost-effectiveness ratio of $40 361 per life-year gained and $55 600 per quality-adjusted life-year gained.Conclusions: For symptomatic patients with heart failure and 3 to 4+ secondary mitral regurgitation, TMVr increases life expectancy and quality-adjusted life expectancy compared with GDMT at an incremental cost per quality-adjusted life-year gained that represents acceptable economic value according to current US thresholds.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01626079. [ABSTRACT FROM AUTHOR]

Background: In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, transcatheter mitral valve repair (TMVr) led to reduced heart failure (HF) hospitalizations and improved survival in patients with symptomatic HF and 3+ to 4+ secondary mitral regurgitation (MR) on maximally-tolerated medical therapy. Given the advanced age and comorbidities of these patients, improvement in health status is also an important treatment goal.Objectives: The purpose of this study was to understand the health status outcomes of patients with HF and 3+ to 4+ secondary MR treated with TMVr versus standard care.Methods: The COAPT trial randomized patients with HF and 3+ to 4+ secondary MR to TMVr (n = 302) or standard care (n = 312). Health status was assessed at baseline and at 1, 6, 12, and 24 months with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the SF-36 health status survey. The primary health status endpoint was the KCCQ overall summary score (KCCQ-OS; range 0 to 100; higher = better; minimum clinically important difference = 5 points).Results: At baseline, patients had substantially impaired health status (mean KCCQ-OS 52.4 ± 23.0). While health status was unchanged over time in the standard care arm, patients randomized to TMVr demonstrated substantial improvement in the KCCQ-OS at 1 month (mean between-group difference 15.9 points; 95% confidence interval [CI]: 12.3 to 19.5 points), with only slight attenuation of this benefit through 24 months (mean between-group difference 12.8 points; 95% CI: 7.5 to 18.2 points). At 24 months, 36.4% of TMVr patients were alive with a moderately large (≥10-point) improvement versus 16.6% of standard care patients (p < 0.001), for a number needed to treat of 5.1 patients (95% CI: 3.6 to 8.7 patients). TMVr patients also reported better generic health status at each timepoint (24-month mean difference in SF-36 summary scores: physical 3.6 points; 95% CI: 1.4 to 5.8 points; mental 3.6 points; 95% CI: 0.8 to 6.4 points).Conclusions: Among patients with symptomatic HF and 3+ to 4+ secondary MR receiving maximally-tolerated medical therapy, edge-to-edge TMVr resulted in substantial early and sustained health status improvement compared with medical therapy alone. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] [COAPT]; NCT01626079). [ABSTRACT FROM AUTHOR]

Background: Among patients with heart failure who have mitral regurgitation due to left ventricular dysfunction, the prognosis is poor. Transcatheter mitral-valve repair may improve their clinical outcomes.Methods: At 78 sites in the United States and Canada, we enrolled patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy. Patients were randomly assigned to transcatheter mitral-valve repair plus medical therapy (device group) or medical therapy alone (control group). The primary effectiveness end point was all hospitalizations for heart failure within 24 months of follow-up. The primary safety end point was freedom from device-related complications at 12 months; the rate for this end point was compared with a prespecified objective performance goal of 88.0%.Results: Of the 614 patients who were enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of all hospitalizations for heart failure within 24 months was 35.8% per patient-year in the device group as compared with 67.9% per patient-year in the control group (hazard ratio, 0.53; 95% confidence interval [CI], 0.40 to 0.70; P<0.001). The rate of freedom from device-related complications at 12 months was 96.6% (lower 95% confidence limit, 94.8%; P<0.001 for comparison with the performance goal). Death from any cause within 24 months occurred in 29.1% of the patients in the device group as compared with 46.1% in the control group (hazard ratio, 0.62; 95% CI, 0.46 to 0.82; P<0.001).Conclusions: Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy, transcatheter mitral-valve repair resulted in a lower rate of hospitalization for heart failure and lower all-cause mortality within 24 months of follow-up than medical therapy alone. The rate of freedom from device-related complications exceeded a prespecified safety threshold. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079 .). [ABSTRACT FROM AUTHOR]

Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous etiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodeling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of transcatheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives. [ABSTRACT FROM AUTHOR]