MitraClip Therapy Research Articles

Outcomes of mitral TEER in non-responders to cardiac resynchronization therapy: A systematic review and meta-analysis

BackgroundSecondary mitral regurgitation (MR) worsens in 10–15 % of heart failure (HF) patients receiving cardiac resynchronization therapy (CRT). Transcatheter edge-to-edge repair (TEER) with Mitra-Clip (Abbot Vascular, Santa Clara, CA, USA) therapy is associated with improved survival and decreased rates of hospitalization for HF in selected patients with secondary MR. Data on TEER outcomes in CRT-non-responders are limited. The purpose of this meta-analysis was to evaluate outcomes of mitral TEER with Mitra-Clip in CRT-non-responders. MethodsCochrane, Scopus, MEDLINE, and EMBASE were searched for studies discussing outcomes of Mitra-Clip in CRT non-responders. Two reviewers were independently involved in screening studies and extracting relevant data. Individual study incidence rate estimates underwent logit transformation to calculate the weighted summary proportion under the random effect model. ResultsA total of eight reports met the inclusion criteria (439 patients). Mitra-Clip improved MR grade to ≤2+ in 83.8 % and 86.8 % of CRT non-responders at six months and one year, respectively. Symptomatic improvement (New York Heart Association class ≤II) was also found in 71 % and 78.1 % of CRT non-responders at six months and one year, respectively. The pooled overall incidence estimates of mortality at 30 days, 6 months, 1 year, and 2 years were 3.6 %, 9.2 %, 17.8 %, and 25.9 %, respectively. ConclusionTEER with Mitra-Clip in patients with significant secondary MR who do not respond to CRT was associated with MR improvement, alleviation of symptoms, and mortality rates similar to those in the COAPT trial.

Abstract 16372: Prognostic Value of Baseline Right Ventricular Dysfunction Using TAPSE and TAPSE to PASP Ratio in Patients Undergoing Mitra-Clip: Systematic Review and Meta-Analysis

Introduction: Transcatheter edge-to-edge mitral valve repair (TEER) using Mitra-clip is an established therapy for high-risk surgical candidates who are refractory to optimal medical treatment. Several reports have shown that right ventricular dysfunction (RVD) is associated with increased morbidity and mortality in heart failure (HF) patients. Emerging data on the relationship between baseline RVD and post-TEER mortality has been published. Objective: Our main goal is to assess the prognostic impact of baseline RV function markers; tricuspid annular plane excursion (TAPSE) and TAPSE/PASP (pulmonary arterial systolic pressure) ratio, as an expression of the right ventricle-pulmonary artery coupling following Mitra-Clip. Methods: MEDLINE and EMBASE were searched for studies discussing outcomes of Mitra-Clip in patients with and without RV dysfunction as expressed by TAPSE or TAPSE:PASP ratio. Two reviewers independently screened the studies and extracted the pertinent survival data. Odds ratios (OR) with 95% confidence interval were calculated using a random-effects model. Results: Twelve reports enrolling 3515 patients (1443 with and 2072 without pre-existing RVD) were included. Patients with RVD had OS reduction after Mitra-Clip by 55% at 6 months, 60% at one year, and 63% at two years [OR: 0.45 (0.35-0.58), 0.40 (0.33-0.48), 0.37 (0.31-0.45) respectively; P < .001] compared to normal RV group. Likewise, HR readmission free survival was minimized among RVD patients by 53% at 6 months, 56% at one year, and 59% at two years compared to normal RV group [OR: 0.47 (0.35-0.65), 0.44 (0.35-0.55), 0.41 (0.30-0.56) respectively; P < .00001]. TAPSE:PASP ≤ 0.30-0.37 was associated with lower OS and HF re-admission free survival at 6 months (OR: 0.37, 0.44; P < .00001) and 1 year (OR: 0.35, 0.41; P < .00001) after Mitra-Clip. Furthermore, TAPSE ≤ 15-16 negatively impacted the OS at 6 months (OR: 0.40 P < .00001) and 1 year (OR: 0.50; P < .00001) after Mitra-Clip. Conclusions: Pre-existing RV dysfunction as expressed by TAPSE ≤15-16 or TAPSE:PASP ratio ≤ 0.30-0.37 decreased the overall survival and HF readmission free survival after Mitra-Clip therapy. Further research is warranted to guide interventional timing based on the degree of RV dysfunction.

Short- and Medium-Term Mortality in ESRD Patients Undergoing MitraClip Therapy – a Multicenter Retrospective Cohort Study

Short- and Medium-Term Mortality in ESRD Patients Undergoing MitraClip Therapy – a Multicenter Retrospective Cohort Study

Incidence, Predictors, and Outcomes Associated With Worsening Renal Function in Patients With Heart Failure and Secondary Mitral Regurgitation: The COAPT Trial.

Background The incidence and implications of worsening renal function (WRF) after mitral valve transcatheter edge-to-edge repair (TEER) in patients with heart failure (HF) are unknown. Therefore, the aim of this study was to determine the proportion of patients with HF and secondary mitral regurgitation who develop persistent WRF within 30 days following TEER, and whether this development portends a worse prognosis. Methods and Results In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, 614 patients with HF and severe secondary mitral regurgitation were randomized to TEER with the MitraClip plus guideline-directed medical therapy (GDMT) versus GDMT alone. WRF was defined as serum creatinine increase ≥1.5× or ≥0.3 mg/dL from baseline persisting to day 30 or requiring renal replacement therapy. All-cause death and HF hospitalization rates between 30 days and 2 years were compared in patients with and without WRF. WRF at 30 days was present in 11.3% of patients (9.7% in the TEER plus GDMT group and 13.1% in the GDMT alone group; P=0.23). WRF was associated with all-cause death (hazard ratio [HR], 1.98 [95% CI, 1.3-3.03]; P=0.001) but not HF hospitalization (HR, 1.47 [ 95% CI, 0.97-2.24]; P=0.07) between 30 days and 2 years. Compared with GDMT alone, TEER reduced both death and HF hospitalization consistently in patients with and without WRF (Pinteraction=0.53 and 0.57, respectively). Conclusions Among patients with HF and severe secondary mitral regurgitation, the incidence of WRF at 30 days was not increased after TEER compared with GDMT alone. WRF was associated with greater 2-year mortality but did not attenuate the treatment benefits of TEER in reducing death and HF hospitalization compared with GDMT alone. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.

Impact of Malnutrition in Patients With Heart Failure and Secondary Mitral Regurgitation: The COAPT Trial

BackgroundAlthough 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. ObjectivesThe 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. MethodsBaseline 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. ResultsAmong 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-Pinteraction = 0.46) and HFH (adj-Pinteraction = 0.67) with TEER were consistent in patients with and without malnutrition. ConclusionsMalnutrition 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)

Machine learning used for simulation of MitraClip intervention: A proof-of-concept study.

Introduction: Severe mitral regurgitation (MR) is a mitral valve disease that can lead to lifethreatening complications. MitraClip (MC) therapy is a percutaneous solution for patients who cannot tolerate surgical solutions. In MC therapy, a clip is implanted in the heart to reduce MR. To achieve optimal MC therapy, the cardiologist needs to foresee the outcomes of different scenarios for MC implantation, including the location of the MC. Although finite element (FE) modeling can simulate the outcomes of different MC scenarios, it is not suitable for clinical usage because it requires several hours to complete. Methods: In this paper, we used machine learning (ML) to predict the outcomes of MC therapy in less than 1s. Two ML algorithms were used: XGBoost, which is a decision tree model, and a feed-forward deep learning (DL) model. The MC location, the geometrical attributes of the models and baseline stress and MR were the features of the ML models, and the predictions were performed for MR and maximum von Mises stress in the leaflets. The parameters of the ML models were determined to achieve the minimum errors obtained by applying the ML models on the validation set. Results: The results for the test set (not used during training) showed relative agreement between ML predictions and ground truth FE predictions. The accuracy of the XGBoost models were better than DL models. Mean absolute percentage error (MAPE) for the XGBoost predictions were 0.115 and 0.231, and the MAPE for DL predictions were 0.154 and 0.310, for MR and stress, respectively. Discussion: The ML models reduced the FE runtime from 6 hours (on average) to less than 1s. The accuracy of ML models can be increased by increasing the dataset size. The results of this study have important implications for improving the outcomes of MC therapy by providing information about the outcomes of MC implantation in real-time.

Association between serum albumin and outcomes in heart failure and secondary mitral regurgitation: the COAPT trial.

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. 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 4.0g/dl, interquartile range 3.7-4.2g/dl). Patients with albumin <4.0g/dl compared with ≥4.0g/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 <4.0g/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). 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.

Bailout Reclipping for Mitral Leaflet Perforation: A Strategy to Overcome Complications During MitraClip Therapy

Bailout Reclipping for Mitral Leaflet Perforation: A Strategy to Overcome Complications During MitraClip Therapy

CRT-700.23 Short- and Medium-Term Mortality in ESRD Patients Undergoing MitraClip Therapy – a Multicenter Retrospective Cohort Study

CRT-700.23 Short- and Medium-Term Mortality in ESRD Patients Undergoing MitraClip Therapy – a Multicenter Retrospective Cohort Study

939 PROGNOSTIC IMPACT OF THE COAPT INCLUSION AND EXCLUSION CRITERIA IN REAL WORLD PATIENTS WITH SECONDARY MITRAL REGURGITATION UNDERGOING MITRACLIP IMPLANTATION

Abstract Background The COAPT randomized trial has shown a huge benefit in the survival of patients with heart failure and functional mitral regurgitation treated with Mitraclip. However, patients in COAPT trial were highly selected and the clinical course in real-world patients with and without fulfilment of the trial inclusion criteria is unclear. Methods and Results The present study examined the clinical outcome in consecutive patients (n=146) with symptomatic moderate-to-severe or severe MR of dominant functional etiology undergoing Mitraclip therapy by the presence of the inclusion criteria of the COAPT trial (left ventricular ejection fraction &amp;gt;20%, left ventricular end-systolic dimension &amp;lt;70 mm, non-commissural primary jet, estimated pulmonary artery systolic pressure &amp;lt;70 mmHg, mitral valve orifice area &amp;gt;4 cm2, no prior mitral valve leaflet surgery or any currently implanted prosthetic mitral valve or any prior transcatheter mitral valve procedure). The primary endpoint was the composite of all-cause mortality or heart failure hospitalization. Secondary endpoints were the single components of the primary endpoint (heart failure hospitalization, all-cause mortality) and cardiovascular mortality. Among 146 patients who underwent Mitraclip implantation 35.6% fulfilled the inclusion criteria of COAPT. The composite endpoint was significantly less frequent in patients fulfilling the COAPT selection criteria than in those not fulfilling the criteria [HR 0.3851 (0.2266 to 0.6642); p=0.0017] (Figure). Conclusion In this single center study the outcome of patients with functional mitral regurgitation undergoing Mitraclip therapy was significantly worse in patients not fulfilling COAPT inclusion criteria, indicating that these criteria might help identify futility.

900 PREDICTORS OF OUTCAMES IN PATIENTS WITH MITRAL REGURGITATION UNDERGOING PERCUTANEOUS VALVE REPAIR

Abstract Aims Mitral regurgitation is the second-most frequent VHD in Europe. According to the latest ESC Guidelines, transcatheter edge-to-edge repair (TEER) was included as a treatment option in patients with severe symptomatic MR at high risk for surgery (Class IIb recommendation) for primary MR and a Class IIa recommendation for secondary MR. We sought to investigate predictors of clinical outcome in patients with mitral regurgitation undergoing percutaneous valve repair. Methods and Results The MITRA-UMG study, a single-center registry, retrospectively collected consecutive patients with symptomatic moderate-to-severe or severe MR undergoing MitraClip therapy between March 2012 to October 2021 at Magna Graecia University. Clinical, echocardiographic and procedural data were collected and compared with post procedural outcomes. Procedural success was defined as successful implantation of one or more clip(s) with a post-procedure reduction of MR of 2 + or less at discharge. The primary endpoint was the composite of cardiovascular death or rehospitalization for heart failure. The median follow-up was 456 days (IQR 372–1130 days) with a complete 1-year follow- up in 188 of 200 (97%) patients. A functional aetiology was classified in 75% of patients. Procedural success was obtained in 98% of patients. The composite primary endpoint of cardiovascular death or rehospitalization for HF was met in 77 patients (36%) with cumulative incidences of 7% at 30 days and 25% at 1 year. In the Cox multivariate model, NYHA functional class and left ventricular end-diastolic volume index (LVEDVi), independently increased the risk of the primary endpoint at long-term follow-up. At Kaplan–Meier analysis, a LVEDVi &amp;gt; 92 ml/m2 was associated with an increased incidence of the primary endpoint (HR 3.55, 95%CI [2.03, 6.18], P&amp;lt;0.0001) (Figure). Conclusions In this study, patients presenting with dilatated ventricles (LVEDVi &amp;gt; 92 ml/m2) and advanced heart failure symptoms (NYHA IV) carried the worst prognosis after TEER.

MitraClip for the treatment of heart failure with mitral regurgitation: A cost-effectiveness analysis in a Chinese setting.

Heart failure (HF) with mitral regurgitation is associated with decreased survival. Guideline-directed medical therapy and transcatheter edge-to-edge repair (TEER) are the main options for HF patients with severe mitral regurgitation who are considered high-risk or prohibitive. To date, there have been no studies investigating the cost-effectiveness of MitraClip vs. optimal medical therapy (OMT) in a Chinese setting. A combined decision tree and Markov model were developed to compare the cost-effectiveness MitraClip vs. OMT with a lifetime simulation. The primary outcome was the incremental cost-effectiveness ratio (ICER), which represented incremental costs per quality-adjusted life-year (QALY). The willingness-to-pay (WTP) threshold was set three times of per capita gross domestic product (GDP) in China in 2021, which was 242,928 CNY. MitraClip would be considered cost-effective if the ICER obtained was lower than the WTP threshold. Otherwise, it would be not considered cost-effective. One-way sensitivity and probabilistic sensitivity analyses were performed to validate the robustness of the results. After a simulation of the lifetime, the overall cost for a patient in the MitraClip cohort was 423,817 CNY, and the lifetime cost in the OMT was 28,369 CNY. The corresponding effectiveness in both cohorts was 2.32 QALY and 1.80 QALY per person, respectively. The incremental cost and increment effectiveness were 395,448 CNY and 0.52 QALY, respectively, and the ICER was 754,410 CNY/QALY. The ICER obtained was higher than the WTP threshold. Sensitivity analysis validated our finding. MitraClip provided effectiveness but with more costs compared with OMT, and the incremental cost-effectiveness ratio obtained was higher than the WTP threshold. MitraClip was considered not cost-effective in Chinese HF patients with secondary mitral regurgitation.

Assessment of the MitraClip Procedure: Reassessing the Goals

THE MITRACLIP (Abbott Laboratories) was first implanted in 2003, was approved in Europe in 2008, and approved by the US Food and Drug Administration in 2013. The MitraClip procedure has reduced hospitalization and mortality compared to medical therapy, with either improved or similar outcomes compared with isolated mitral valve surgery. 1 Shah MA Dalak FA Alsamadi F et al. Complications following percutaneous mitral valve edge-to-edge repair using MitraClip. J Am Coll Cardiol. 2021; 3: 370-376 Google Scholar , 2 Stone GW Lindenfeld JA Abraham WT et al. Transcatheter mitral-valve repair in patients with heart failure. N Engl J Med. 2018; 379: 2307-2318 Crossref PubMed Scopus (1514) Google Scholar , 3 Stone GW Adams DH Abraham WT et al. Clinical trial design principles and endpoint definitions for transcatheter mitral valve repair and replacement: Part 2: Endpoint definitions a consensus document from the mitral valve academic research consortium. J Am Coll Cardiol. 2015; 66: 308-321 Crossref PubMed Scopus (302) Google Scholar In the earlier and preliminary data, proponents of surgery highlighted less mitral regurgitation (MR) and fewer additional procedures after surgical correction of MR; however, the overall major cardiac adverse events were significantly lower (15% v 48%) for percutaneous procedures. 4 Feldman T Foster E Glower DD et al. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med. 2011; 364: 1395-1406 Crossref PubMed Scopus (1475) Google Scholar Since the initial experiences, all outcomes for MitraClip procedures have improved with greater experience. 5 Chhatriwalla AK Vemulapalli S Holmes DR et al. Institutional experience with transcatheter mitral valve repair and clinical outcomes. J Am Coll Cardiol. 2019; 12: 1342-1352 Crossref Scopus (100) Google Scholar Right Ventricular Failure in Emergent MitraClip Therapy—A Problem Worth InvestigatingJournal of Cardiothoracic and Vascular AnesthesiaPreviewThe MitraClip (Abbott, Santa Clara, CA) has emerged as a safe, effective, and durable treatment for hemodynamically significant mitral regurgitation (MR) refractory to maximally tolerable guideline-directed medical therapy in nonsurgical patients.1-9 Hemodynamically, the MitraClip reduces left ventricular volumes, unloads the left atrium and pulmonary circulation, reduces right ventricular afterload (as long as iatrogenic MitraClip-induced mitral stenosis does not develop), and facilitates biventricular reverse remodeling. Full-Text PDF Invited Commentary: “Assessment of the MitraClip procedure: Reassessing the goals”Journal of Cardiothoracic and Vascular AnesthesiaPreviewAsher and colleagues1 present two interesting cases that not only highlight the use of MitraClip in the urgent setting, but also how intraoperative case management can help facilitate procedural success. Mitral valve disease is one of the most common valvular disorders with an incidence anywhere from 10% to 24%, most commonly affecting people older than 75 years.2,3 Primary mitral regurgitation (MR) is due to a structural or degenerative abnormality while secondary MR is related to left ventricular (LV) or less commonly left atrial disease. Full-Text PDF

Maximally tolerated guideline-directed medical therapy and barriers to optimization in patients with heart failure with reduced ejection fraction: the COAPT trial

Abstract Background The COAPT trial of MitraClip therapy employed a central screening eligibility committee (CSEC) of heart failure (HF) experts to ensure the use of maximally tolerated guideline-directed medical therapy (GDMT) and systematically document intolerances in all potential patients prior to approval for randomization. Purpose To describe the percentage of GDMT classes, doses tolerated, predictors of intolerance, and specific intolerances limiting GDMT among patients approved for randomization by the CSEC. Methods We analyzed baseline use, dose, and intolerances of i) angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB) or angiotensin receptor neprilysin inhibitor (ARNI); ii) beta-blockers (BB); and iii) mineralocorticoid receptor antagonists (MRA) in the CSEC-approved COAPT population with HF with reduced ejection fraction (HFrEF; LVEF ≤40%). We analyzed variables associated with GDMT tolerance. Results In COAPT, 464 patients had HFrEF and complete screening medication information. Any dose of all 3, 2 or 1 GDMT classes were tolerated in 39%, 39% and 20% of patients respectively; only 2% of patients (n=9) could not tolerate any GDMT (Figure 1). BB were prescribed in the most (93%) patients followed by ACEI/ARB/ARNI (69%) and MRA (55%). Intolerances limiting each GDMT class differed, but hypotension and kidney dysfunction were most common (Figure 2). No patients tolerated goal doses of all 3 GDMT classes. For BB, only 32% tolerated ≥50% of the goal dose; while for ACEI/ARB/ARNI, no patients achieved goal doses, and only 1% tolerated ≥50% of the goal dose. For MRA, 86% of patients tolerated 25mg/day or less. Patients intolerant of BB were less likely to tolerate an ACEI/ARB/ARNI (OR 0.39, 95% CI 0.20–0.76; p=0.004) but not a MRA (p=0.21) compared with patients tolerating a low dose BB. Patients intolerant of MRA were less likely to tolerate ACEI/ARB/ARNI therapy (OR 0.37, 95% CI 0.25–0.57; p&amp;lt;0.0001) but not a BB (p=0.31) compared with patients tolerating MRA. Patients tolerating low dose ACEI/ARB/ARNI had a higher baseline mean eGFR (52±21 versus 40±21 ml/min/m2; p&amp;lt;0.0001) compared with patients intolerant of ACEI/ARB/ARNI. Likewise, patients tolerating MRA had a higher baseline mean eGFR (52±21 versus 42±21 ml/min/m2; p&amp;lt;0.0001) compared with patients intolerant of MRA. Conclusion In a contemporary trial in which HF specialists ensured GDMT optimization, many patients had medical intolerances prohibiting use of one or more GDMT classes, and few patients tolerated target doses. These findings indicate medical intolerances are the primary cause of low GDMT prescription rates in patients with moderate to severe HFrEF. Yet, use of GDMT in this very ill population was much better than “real world” registries of HFrEF suggesting that mandating careful CSEC review prior to study enrollment is important for clinical trials having the objective of randomizing a maximally treated patient cohort. Funding Acknowledgement Type of funding sources: None.

Prediction of Death or HF Hospitalization in Patients With Severe FMR: The COAPT Risk Score.

There are limited data on the predictors of death or heart failure hospitalization (HFH) in patients with heart failure (HF) with functional mitral regurgitation (FMR). The aim of this study was to develop a predictive risk score using the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for HeartFailure Patients With Functional Mitral Regurgitation) trial database. In COAPT, 614 symptomatic patients with HF and moderate to severe or severe FMR were randomized to MitraClip implantation plus guideline-directed medical therapy (GDMT) or GDMT alone. A risk score for the 2-year rate of death or HFH was generated from Cox proportional hazards models. The predictive value of the model was assessed using the area under the curve of receiver-operating characteristic plots. Kaplan-Meier curves were generated to estimate the proportion of patients experiencing death or HFH across quartiles of risk. During 2-year follow-up, 201 patients (64.4%) in the GDMT-alone group and 133 patients (44.0%) in the MitraClip group experienced death or HFH (P< 0.001). A risk score containing 4 clinical variables (New York Heart Association functional class, chronic obstructive pulmonary disease, atrial fibrillation or flutter, and chronic kidney disease) and 4 echocardiographic variables (left ventricular ejection fraction, left ventricular end-systolic dimension, right ventricular systolic pressure, and tricuspid regurgitation) in addition to MitraClip treatment was generated. The area under the curve of the risk score model was 0.74, and excellent calibration was present. The relative benefit of MitraClip therapy in reducing the 2-year hazard of death or HFH was consistent across the range of baseline risk. A simple risk score of clinical, echocardiographic, and treatment variables may provide useful prognostication in patients with HF and severe FMR.

Effects of MitraClip Therapy on Mitral Flow Patterns and Vortex Formation: An In Vitro Study.

MitraClip transcatheter edge-to-edge repair is used to treat mitral regurgitation (MR). While MR is reduced, diastolic left ventricular flows are altered. An in vitro left heart simulator was used to assess a porcine mitral valve in the native, MR, and MR plus MitraClip cases. Velocity, vorticity, and Reynolds shear stress (RSS) were quantified by particle image velocimetry. Peak velocity increased from 1.20 m/s for native to 1.30 m/s with MR. With MitraClip, two divergent jets of 1.18 and 0.61 m/s emerged. Higher vorticity was observed with MR than native and lessened with MitraClip. MitraClip resulted in shear layer formation and downstream vortex formation. Native RSS decreased from 33 Pa in acceleration to 29 Pa at peak flow, then increased to 31 Pa with deceleration. MR RSS increased from 27 Pa in acceleration to 40 Pa at peak flow to 59 Pa during deceleration. MitraClip RSS increased from 79 Pa in acceleration to 162 Pa during peak flow, then decreased to 45 Pa during deceleration. After MitraClip, two divergent jets of reduced velocity emerged, accompanied by shear layers and recirculation. Chaotic flow developed, resulting in elevated RSS magnitude and coverage. Findings help understand consequences of MitraClip on left ventricular flow dynamics.

MitraClip Treatment of Moderate-to-Severe and Severe Mitral Regurgitation in High Surgical Risk Patients - Real-World 1-Year Outcomes From Japan.

The MitraClip NT System was approved for marketing in Japan on October 31, 2017, and a prospective, multi-center, single-arm Post-Marketing use Surveillance (PMS) study was launched in 2018. This is the first report of the Japan PMS study with 1-year subject outcomes.Methods and Results:A total of 500 patients were registered between April 2018 and January 2019. Patients with symptomatic chronic moderate-to-severe (3+) or severe mitral regurgitation (MR; 4+), MR with a Society of Thoracic Surgery (STS) replacement score of ≥8%, or presence of 1 pre-defined risk factor were enrolled. Primary outcome measures included acute procedural success (APS), and rate of Single Leaflet Device Attachment (SLDA) at 30 days. The overall cohort was elderly (77.9±9.48 years) with functional MR etiology in 71.6% of the subjects. The majority of subjects were New York Heart Association (NYHA) class III/IV (68.9%), with mean STS replacement score of 11.95±9.66%. The APS rate was 91.13% and the 30-day SLDA rate was 1.21%. Durable MR reduction was achieved with 88.1% of subjects at MR ≤2+ at 1 year. Significant improvement in the functional capacity was observed, with 93% of subjects at NYHA class I/II at 1 year. In the Japan PMS experience, the MitraClip procedure resulted in improvements in MR severity, with significantly improved functional outcomes. These results demonstrate safety and efficacy of MitraClip therapy in the eligible Japanese population.

Impact of baseline renal dysfunction on cardiac outcomes and end-stage renal disease in heart failure patients with mitral regurgitation: the COAPT trial.

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). 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 (Pinteraction = 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). 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.

Age-Related Outcomes After Transcatheter Mitral Valve Repair in Patients With HeartFailure: Analysis From COAPT.

The aim of this study was to assess the impact of age on outcomes in patients undergoing transcatheter edge-to-edge repair (TEER) from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for HeartFailure Patients with Functional Mitral Regurgitation) trial. In the COAPT trial, TEER with the MitraClip device in patients with heart failure (HF) and moderate to severe or severe secondary mitral regurgitation (SMR) reduced the risk for HF hospitalization (HFH) and all-cause mortality compared with maximally tolerated guideline-directed medical therapy (GDMT) alone. There are limited data regarding the effectiveness of MitraClip therapy in elderly patients. Patients (n=614) were grouped by median age at randomization (74 years) and by MitraClip treatment vs GDMT alone. The primary endpoint was the 2-year rate of death or HFH assessed by multivariable Cox regression. Death or HFH within 2 years occurred less frequently after treatment with the MitraClip vs GDMT alone in patients<74 years of age (37.3% vs 64.5%; adjusted HR: 0.41; 95%CI: 0.29-0.59) and≥74 years of age (51.7% vs 69.6%; adjusted HR: 0.58; 95%CI: 0.42-0.81) (Pint=0.17). Mortality was also consistently reduced with MitraClip treatment in young and elderly patients (Pint=0.42). In contrast, elderly patients treated with the MitraClip vs GDMT alone tended to have a lesser reduction of HFH than younger patients (Pint=0.03). Younger and older patients had similar improvements in quality of life after treatment with the MitraClip compared with GDMT alone. In the COAPT trial, MitraClip treatment of moderate to severe and severe SMR reduced the composite risk for death or HFH and improved survival and quality of life regardless of age. As such, young and elderly patients with HF and severe SMR benefit from TEER, although elderly patients may not have as great a benefit from the MitraClip device in reducing HFH.

Clinical Implications of Functional Mitral Regurgitation Severity in Patients with Heart Failure with Reduced Ejection Fraction (HFrEF).

Background:An estimated 64.3 million people are living with heart failure worldwide. Functional MR in chronic HFrEF reflects primarily the severity of LV dysfunction and is not related to structural alterations of the mitral valvular apparatus. FMR in patients with HFrEF independently of the etiology of HFrEF and its underlying mechanisms, contributes to progression of the symptoms of HF and is independent predictor of worse clinical outcomes.Objective:The purpose of this study was to assess the severity of functional mitral regurgitation (FMR) and its clinical implications in patients with chronic heart failure with reduced ejection fraction (HFrEF).Methods:We enrolled 146 consecutive adult patients with CHF with reduced ejection fraction (HFrEF) who presented to outpatient clinics. All patients underwent clinical and physical examination. Baseline examination included medical history, detailed assessment of current medication, electrocardiogram recording, transthoracic echocardiogram and comorbidities. Heart failure with reduced ejection fraction was defined in line with the new guidelines as history of HF signs and symptoms as well as a LV ejection fraction (LVEF) below 40%. Cardiovascular risk factors were recorded according to the respective guidelines. FMR was defined and graded according to the ESC/EACTS Guidelines for the management of valvular heart disease. The extent of FMR was assessed at baseline and after a median follow-up period of 4 years in 146 consecutive HFrEF patients (left ventricular ejection fraction <40%). All of the patients received the heart failure (HF) medications in agreement with 2016 and 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Major adverse cardiac events were defined as a composite of all-cause death and the need for admission for HF.Results:A total of 146 chronic HFrEF patients (mean age of 63±11 years, 62% male, mean LVEF of 25±11%) of which 19% patients had severe FMR at baseline, with a mean EROA of 31.4±2.7 mm2 and a mean Reg Vol of 45.9±5.3 ml. There was a significant interaction between FMR and NYHA functional class in predicting death or need for hospitalization, (P < 0.0001 for the interaction term FMR NYHA III-IV). During a median follow-up period of 4.2 (IQR) 3.1-5.8) years, the primary endpoint occurred in 52 (36%) patients (21 HF admissions, and 31 deaths). There was a strong graded association between the presence and degree of FMR and risk of death or admission (P <0.0001) at 4 years follow-up period. Regarding HF therapy, 129 patients (88%) received RAAS antagonists, 17 patients (12%) received ARNI, 86 patients (59%) received beta-blockers, 75 patients (51%) were treated with MRA. 31 patients (21%) underwent cardiac resynchronization therapy (CRT) with a response rate of 64%. 24 patients (16%) underwent ICD implantation.Conclusion:Guideline-directed medical therapy is the first-line treatment for chronic HF patients who also have FMR. After this first-line approach, surgical or MitraClip transcatheter therapy can be considered in patients with persistent severe and symptomatic FMR in order to improve symptoms, quality of life and functional status.