Concomitant Tricuspid Repair in Patients with Degenerative Mitral Regurgitation.

BACKGROUND: Tricuspid regurgitation is common in patients with severe degenerative mitral regurgitation. However, the evidence base is insufficient to inform a decision about whether to perform tricuspid-valve repair during mitral-valve surgery in patients who have moderate tricuspid regurgitation or less-than-moderate regurgitation with annular dilatation. METHODS: We randomly assigned 401 patients who were undergoing mitral-valve surgery for degenerative mitral regurgitation to receive a procedure with or without tricuspid annuloplasty (TA). The primary 2-year end point was a composite of reoperation for tricuspid regurgitation, progression of tricuspid regurgitation by two grades from baseline or the presence of severe tricuspid regurgitation, or death. RESULTS: Patients who underwent mitral-valve surgery plus TA had fewer primary-end-point events than those who underwent mitral-valve surgery alone (3.9% vs. 10.2%) (relative risk, 0.37; 95% confidence interval [CI], 0.16 to 0.86; P = 0.02). Two-year mortality was 3.2% in the surgery-plus-TA group and 4.5% in the surgery-alone group (relative risk, 0.69; 95% CI, 0.25 to 1.88). The 2-year prevalence of progression of tricuspid regurgitation was lower in the surgery-plus-TA group than in the surgery-alone group (0.6% vs. 6.1%; relative risk, 0.09; 95% CI, 0.01 to 0.69). The frequencies of major adverse cardiac and cerebrovascular events, functional status, and quality of life were similar in the two groups at 2 years, although the incidence of permanent pacemaker implantation was higher in the surgery-plus-TA group than in the surgery-alone group (14.1% vs. 2.5%; rate ratio, 5.75; 95% CI, 2.27 to 14.60). CONCLUSIONS: Among patients undergoing mitral-valve surgery, those who also received TA had a lower incidence of a primary-end-point event than those who underwent mitral-valve surgery alone at 2 years, a reduction that was driven by less frequent progression to severe tricuspid regurgitation. Tricuspid repair resulted in more frequent permanent pacemaker implantation. Whether reduced progression of tricuspid regurgitation results in long-term clinical benefit can be determined only with longer follow-up. (Funded by the National Heart, Lung, and Blood Institute and the German Center for Cardiovascular Research; ClinicalTrials.gov number, NCT02675244.).

Sex Differences and Similarities in Valvular Heart Disease.

As populations age worldwide, the burden of valvular heart disease has grown exponentially, and so has the proportion of affected women. Although rheumatic valve disease is declining in high-income countries, degenerative age-related causes are rising. Calcific aortic stenosis and degenerative mitral regurgitation affect a significant proportion of elderly women, particularly those with comorbidities. Women with valvular heart disease have been underrepresented in many of the landmark studies which form the basis for guideline recommendations. As a consequence, surgical referrals in women have often been delayed, with worse postoperative outcomes compared with men. As described in this review, a more recent effort to include women in research studies and clinical trials has increased our knowledge about sex-based differences in epidemiology, pathophysiology, diagnostic criteria, treatment options, outcomes, and prognosis.

Clinical characteristics and outcome of omphalocele and gastroschisis: a 20-year multicenter regional experience.

Omphalocele and gastroschisis are the most common types of abdominal wall defects. Comprehensive local experience helps parents to make decisions on the pregnancy and foresee the disease journey. A retrospective review of abdominal wall defect patients in all three pediatric surgical centers in Hong Kong between January 2003 and February 2023 was conducted. All patients consecutively diagnosed with omphalocele and gastroschisis were included, excluding other forms. Data of demographics and short- and long-term outcome parameters were collected. A total of 99 cases were reviewed and 85 patients met the inclusion criteria. Diagnoses include omphalocele major (n = 49, 57.6%), omphalocele minor (n = 22, 25.9%) and gastroschisis (n = 14, 16.5%), with mean gestational age 37 weeks (SD 2.2) and birth weight 2.7 kg (SD 0.6). Omphalocele is most commonly associated with cardiovascular (n = 28, 39.4%) and chromosomal defects (n = 11, 15.5%). Surgical procedures including primary repair (n = 38, 53.5%), staged closure (n = 30, 42.3%) with average 8.6 days (SD 4.7) of silo reduction, and conservative management (n = 3, 4.2%) were performed. The mortality rate was 14.1% (n = 10) and the complication rate was 36.6% (n = 26). The majority of patients had normal intellectual development (92.5%) and growth (79.2%) on the latest follow-up. For gastroschisis, one patient (7.1%) had intestinal atresia. Surgical procedures included primary repair (n = 9, 64.3%) and staged closure (n = 5, 35.7%) with average 8 days (SD 3.5) of silo reduction. Complication rate was 21.4% (n = 3), with one mortality (7.1%). All patients had normal intellectual development and growth. The mean follow-up time of this series is 76.9 months (SD 62.9). Most abdominal wall defects in our series were managed surgically with a good overall survival rate and long-term outcome. This information is essential during antenatal and postnatal counseling for parents.

Prospective Randomized Controlled Trial Comparing Laparoscopic Palomo Surgery vs Scrotal Antegrade Sclerotherapy in Adolescent Varicocele.

PURPOSE: Varicocele is a common condition in adolescence and the most common correctable cause of infertility. This study aimed to analyze and compare the outcomes of scrotal antegrade sclerotherapy and laparoscopic Palomo surgery in a tertiary referral center. MATERIALS AND METHODS: Patients with left grade 3 varicocele indicated for surgery were prospectively enrolled and randomly allocated to the scrotal antegrade sclerotherapy and laparoscopic Palomo surgery groups, with their respective contralateral normal testes taken as controls. The primary outcome measures were clinical varicocele recurrence, testicular catch-up growth, and postoperative hydrocele. All patients were evaluated clinically and using Doppler ultrasound by radiologists. RESULTS: From 2015 to 2020, 113 patients completed the study and were statistically analyzed (scrotal antegrade sclerotherapy, n = 57; laparoscopic Palomo surgery, n = 56). All patients had significantly smaller testes preoperatively; the testicular volume differences with control testes were -23% in scrotal antegrade sclerotherapy and -19% in laparoscopic Palomo surgery. At 12-month follow-up, there were no statistically significant differences in clinical recurrences between the 2 groups (scrotal antegrade sclerotherapy = 5.3% vs laparoscopic Palomo surgery = 5.4%, P > .05, noninferiority test). Testicular catch-up growths were observed in both groups; the mean testicular volume difference between the treatment and control testes decreased from -23% to -8.1% in scrotal antegrade sclerotherapy (P < .001) and from -19% to -9.3% in laparoscopic Palomo surgery (P < .001) at 12-month follow-up. There was no postoperative hydrocele in the scrotal antegrade sclerotherapy group compared to 7 cases in the laparoscopic Palomo surgery group (0% vs 13%, P = .006). CONCLUSIONS: Both scrotal antegrade sclerotherapy and laparoscopic Palomo surgery are safe and effective procedures for treatment of adolescent varicocele with significant positive effect on testicular catch-up growth. Scrotal antegrade sclerotherapy is not inferior to laparoscopic Palomo surgery in terms of clinical recurrence rate and has significantly less postoperative hydrocele.

2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Aim This executive summary of the hypertrophic cardiomyopathy clinical practice guideline provides recommendations and algorithms for clinicians to diagnose and manage hypertrophic cardiomyopathy in adult and pediatric patients as well as supporting documentation to encourage their use. Methods A comprehensive literature search was conducted from January 1, 2010, to April 30, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Structure Many recommendations from the earlier hypertrophic cardiomyopathy guidelines have been updated with new evidence or a better understanding of earlier evidence. This summary operationalizes the recommendations from the full guideline and presents a combination of diagnostic work-up, genetic and family screening, risk stratification approaches, lifestyle modifications, surgical and catheter interventions, and medications that constitute components of guideline directed medical therapy. For both guideline-directed medical therapy and other recommended drug treatment regimens, the reader is advised to follow dosing, contraindications and drug-drug interactions based on product insert materials.

Residual Shunt After Patent Foramen Ovale Closure and Long-Term Stroke Recurrence: A Prospective Cohort Study.

BACKGROUND: Residual shunt is observed in up to 25% of patients after patent foramen ovale (PFO) closure, but its long-term influence on stroke recurrence currently is unknown. OBJECTIVE: To investigate the association of residual shunt after PFO closure with the incidence of recurrent stroke and transient ischemic attack (TIA). DESIGN: Prospective cohort study comparing stroke or TIA recurrence in patients with and without residual shunt after PFO closure. SETTING: Single hospital center. PARTICIPANTS: 1078 consecutive patients (mean age, 49.3 years) with PFO-attributable cryptogenic stroke who were undergoing percutaneous PFO closure were followed for up to 11 years. MEASUREMENTS: Residual shunt was evaluated by transthoracic echocardiography with saline contrast. Primary outcome was a composite of the first recurrent ischemic stroke or TIA after PFO closure. RESULTS: Compared with complete closure, the presence of residual shunt after PFO closure was associated with an increased incidence of recurrent stroke or TIA: 2.32 versus 0.75 events per 100 patient-years (hazard ratio [HR], 3.05 [95% CI, 1.65 to 5.62]; P < 0.001). This result remained robust after adjustment for important covariates, namely age; study period; device; presence of atrial septal aneurysm, hypertension, hyperlipidemia, diabetes, hypercoagulability, or hypermobile septum; and medication use (HR, 3.01 [CI, 1.59 to 5.69]; P < 0.001). Further stratification based on shunt size revealed that moderate or large residual shunts were associated with a higher risk for stroke or TIA recurrence (HR, 4.50 [CI, 2.20 to 9.20]; P < 0.001); the result for small residual shunts was indeterminate (HR, 2.02 [CI, 0.87 to 4.69]; P = 0.102). LIMITATION: Nonrandomized study with potential unmeasured confounding. CONCLUSION: Among patients undergoing PFO closure to prevent future stroke, the presence of residual shunt, particularly a moderate or large residual shunt, was associated with an increased risk for stroke or TIA recurrence. PRIMARY FUNDING SOURCE: National Institutes of Health.

Secondary valve regurgitation in patients with heart failure with preserved ejection fraction, heart failure with mid-range ejection fraction, and heart failure with reduced ejection fraction.

Secondary mitral regurgitation and secondary tricuspid regurgitation due to heart failure (HF) remain challenging in almost every aspect: increasing prevalence, poor prognosis, notoriously elusive in diagnosis, and complexity of therapeutic management. Recently, defined HF subgroups according to three ejection fraction (EF) ranges (reduced, mid-range, and preserved) have stimulated a structured understanding of the HF syndrome but the role of secondary valve regurgitation (SVR) across the spectrum of EF remains undefined. This review expands this structured understanding by consolidating the underlying phenotype of myocardial impairment with each type of SVR. Specifically, the current understanding, epidemiological considerations, impact, public health burden, mechanisms, and treatment options of SVR are discussed separately for each lesion across the HF spectrum. Furthermore, this review identifies important gaps in knowledge, future directions for research, and provides potential solutions for diagnosis and treatment. Mastering the challenge of SVR requires a multidisciplinary collaborative effort, both, in clinical practice and scientific approach to optimize patient outcomes.

Prognostic importance of the transmitral pressure gradient in mitral annular calcification with associated mitral valve dysfunction.

AIMS: The aim of this study was to define the natural history of patients with mitral annular calcification (MAC)-related mitral valve dysfunction and to assess the prognostic importance of mean transmitral pressure gradient (MG) and impact of concomitant mitral regurgitation (MR). METHODS AND RESULTS: The institutional echocardiography database was examined from 2001 to 2019 for all patients with MAC and MG ≥3 mmHg. A total of 5754 patients were stratified by MG in low (3-5 mmHg, n = 3927), mid (5-10 mmHg, n = 1476), and high (≥10 mmHg, n = 351) gradient. The mean age was 78 ± 11 years, and 67% were female. MR was none/trace in 32%, mild in 42%, moderate in 23%, and severe in 3%. Primary outcome was all-cause mortality, and outcome models were adjusted for age, sex, and MAC-related risk factors (hypertension, diabetes, coronary artery disease, chronic kidney disease). Survival at 1, 5, and 10 years was 77%, 42%, and 18% in the low-gradient group; 73%, 38%, and 17% in the mid-gradient group; and 67%, 25%, and 11% in the high-gradient group, respectively (log-rank P < 0.001 between groups). MG was independently associated with mortality (adjusted HR 1.064 per 1 mmHg increase, 95% CI 1.049-1.080). MR severity was associated with mortality at low gradients (P < 0.001) but not at higher gradients (P = 0.166 and 0.372 in the mid- and high-gradient groups, respectively). CONCLUSION: In MAC-related mitral valve dysfunction, mean transmitral gradient is associated with increased mortality after adjustment for age, sex, and MAC-related risk factors. Concomitant MR is associated with excess mortality in low-gradient ranges (3-5 mmHg) but gradually loses prognostic importance at higher gradients, indicating prognostic utility of transmitral gradient in MAC regardless of MR severity.

Left ventricular wall thickness assessed by cardiac computed tomography and cardiac resynchronization therapy outcomes.

AIMS: Up to 30% of selected heart failure patients do not benefit clinically from cardiac resynchronization therapy (CRT). Left ventricular (LV) wall thickness (WT) analysed using computed tomography (CT) has rarely been evaluated in response to CRT and mitral regurgitation (MR) improvement. We examined the association of LVWT and the ability to reverse LV remodelling and MR improvement after CRT. METHODS AND RESULTS: Fifty-four patients scheduled for CRT underwent pre-procedural CT. Reduced LVWT was defined as WT <6 mm and quantified as a percentage of total LV area. Endpoints were 6-month clinical and echocardiographic response to CRT [New York Heart Association (NYHA) class, LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV)], MR improvement and 2-year major adverse cardiac events (MACE). Patients were divided into three groups according to the percentage of LVWT <6 mm area: ≤20%, 20-50%, and ≥50%. At 6 months, 75%, 71%, and 42% of the patients experienced NYHA improvement in the ≤20%, 20-50%, and ≥50% group, respectively. Additionally, ≤20% group presented higher LVEF, LVEDV, and LVESV positive response rate (86%, 59%, and 83%, respectively). Both 20-50% and ≥50% groups exhibited a lower LVEF, LVEDV, and LVESV positive response rate (52% and 42%; 47% and 45%; and 53% and 45%, respectively). Additionally, ≥25% of LVWT <6 mm inclusive of at least one papillary muscle insertion was the only predictor of lack of MR improvement. Lastly, ≥50% group experienced significantly lower 2-year MACE survival free probability. CONCLUSION: WT evaluated using CT could help to stratify the response to CRT and predict MR improvement and outcomes. CLINICAL TRIAL REGISTRATION: NCT01097733.

Two-Year Outcomes of Surgical Treatment of Severe Ischemic Mitral Regurgitation.

BACKGROUND: In a randomized trial comparing mitral-valve repair with mitral-valve replacement in patients with severe ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI), survival, or adverse events at 1 year after surgery. However, patients in the repair group had significantly more recurrences of moderate or severe mitral regurgitation. We now report the 2-year outcomes of this trial. METHODS: We randomly assigned 251 patients to mitral-valve repair or replacement. Patients were followed for 2 years, and clinical and echocardiographic outcomes were assessed. RESULTS: Among surviving patients, the mean (±SD) 2-year LVESVI was 52.6±27.7 ml per square meter of body-surface area with mitral-valve repair and 60.6±39.0 ml per square meter with mitral-valve replacement (mean changes from baseline, -9.0 ml per square meter and -6.5 ml per square meter, respectively). Two-year mortality was 19.0% in the repair group and 23.2% in the replacement group (hazard ratio in the repair group, 0.79; 95% confidence interval, 0.46 to 1.35; P=0.39). The rank-based assessment of LVESVI at 2 years (incorporating deaths) showed no significant between-group difference (z score=-1.32, P=0.19). The rate of recurrence of moderate or severe mitral regurgitation over 2 years was higher in the repair group than in the replacement group (58.8% vs. 3.8%, P<0.001). There were no significant between-group differences in rates of serious adverse events and overall readmissions, but patients in the repair group had more serious adverse events related to heart failure (P=0.05) and cardiovascular readmissions (P=0.01). On the Minnesota Living with Heart Failure questionnaire, there was a trend toward greater improvement in the replacement group (P=0.07). CONCLUSIONS: In patients undergoing mitral-valve repair or replacement for severe ischemic mitral regurgitation, we observed no significant between-group difference in left ventricular reverse remodeling or survival at 2 years. Mitral regurgitation recurred more frequently in the repair group, resulting in more heart-failure-related adverse events and cardiovascular admissions. (Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00807040.).

Two-Year Outcomes of Surgical Treatment of Moderate Ischemic Mitral Regurgitation.

BACKGROUND: In a trial comparing coronary-artery bypass grafting (CABG) alone with CABG plus mitral-valve repair in patients with moderate ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI) or survival after 1 year. Concomitant mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation, but patients had more adverse events. We now report 2-year outcomes. METHODS: We randomly assigned 301 patients to undergo either CABG alone or the combined procedure. Patients were followed for 2 years for clinical and echocardiographic outcomes. RESULTS: At 2 years, the mean (±SD) LVESVI was 41.2±20.0 ml per square meter of body-surface area in the CABG-alone group and 43.2±20.6 ml per square meter in the combined-procedure group (mean improvement over baseline, -14.1 ml per square meter and -14.6 ml per square meter, respectively). The rate of death was 10.6% in the CABG-alone group and 10.0% in the combined-procedure group (hazard ratio in the combined-procedure group, 0.90; 95% confidence interval, 0.45 to 1.83; P=0.78). There was no significant between-group difference in the rank-based assessment of the LVESVI (including death) at 2 years (z score, 0.38; P=0.71). The 2-year rate of moderate or severe residual mitral regurgitation was higher in the CABG-alone group than in the combined-procedure group (32.3% vs. 11.2%, P<0.001). Overall rates of hospital readmission and serious adverse events were similar in the two groups, but neurologic events and supraventricular arrhythmias remained more frequent in the combined-procedure group. CONCLUSIONS: In patients with moderate ischemic mitral regurgitation undergoing CABG, the addition of mitral-valve repair did not lead to significant differences in left ventricular reverse remodeling at 2 years. Mitral-valve repair provided a more durable correction of mitral regurgitation but did not significantly improve survival or reduce overall adverse events or readmissions and was associated with an early hazard of increased neurologic events and supraventricular arrhythmias. (Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00806988.).

Impact of left atrial compliance improvement on functional status after percutaneous mitral valvuloplasty.

BACKGROUND: Conventional hemodynamic parameters may not accurately predict symptomatic improvement after percutaneous mitral valvuloplasty (PMV). Changes in left heart chamber compliance following adequate relief o0066 mitral stenosis (MS) may be useful in determining functional capacity after PMV. This study aims to determine the acute effects of PMV on compliance of the left heart and whether its changes relate to the patient's functional capacity. METHODS: One-hundred thirty-seven patients with severe MS undergoing PMV were enrolled. Left atrial (Ca ) and left ventricular (Cv ) compliance were invasively estimated and net atrioventricular compliance (Cav ) was calculated before and immediately after the procedure. B-type natriuretic peptide (BNP) levels were obtained before and 24 hr after the procedure. The primary endpoint was functional status at 6-month follow-up, and the secondary endpoint was a composite of death, mitral valve (MV) replacement, repeat PMV, new onset of atrial fibrillation, or stroke in patients in whom PMV was successful. RESULTS: The mean age was 43 ± 12 years, and 119 patients were female (87%). After PMV, Ca and Cav improved significantly from 5.3 [IQR 3.2-8.2] mL/mmHg to 8.7 [5.3-19.2] mL/mmHg (P < 0.001) and 2.2 [1.6-3.4] to 2.8 [2.1-4.1] mL/mmHg (P < 0.001), respectively, whereas Cv did not change (4.6 [3.2-6.8] to 4.4 [3.1-5.6]; P = 0.637). Plasma BNP levels significantly decreased after PMV, with no correlation between its variation and changes in left chamber compliance. At 6-month follow-up, NYHA functional class remained unchanged in 32 patients (23%). By multivariable analyses, changes in Ca immediately after PMV (adjusted OR 1.42; 95% CI 95% 1.02 to 1.97; P = 0.037) and younger age (adjusted OR 0.95; CI 95% 0.92-0.98; P = 0.004), predicted improvement in functional capacity at 6-month follow-up, independent of postprocedural data. The secondary endpoint were predicted by post-PMV mean gradient (adjusted HR 1.363; 95% CI 95% 1.027-1.809; P = 0.032), and lack of functional improvement at 6-month follow-up (adjusted HR 4.959; 95% 1.708-14.403; P = 0.003). CONCLUSIONS: Ca and Cav increase significantly after PMV with no change in Cv . The improvement of Ca is an important predictor of functional status at 6-month follow up, independently of other hemodynamic data. Postprocedural mean gradient and lack of short-term symptomatic improvement were predictors of adverse outcome.

A comparison of postprocedural anticoagulation in high-risk patients undergoing WATCHMAN device implantation.

BACKGROUND: Left atrial appendage closure (LAAC) is an alternative to long-term anticoagulation for thromboembolic protection in patients with atrial fibrillation (AF) and high bleeding risk. Short-term Warfarin use following LAAC is well-studied, while data pertaining to novel oral anticoagulant (NOAC) use in this setting is less robust. Specifically, data regarding the safety and efficacy of postprocedural NOAC use in high-risk patients is lacking. OBJECTIVE: To compare the safety and efficacy of Warfarin and NOAC use in a high-risk patient population undergoing LAAC with the WATCHMAN device. METHODS: From November 2015 to October 2017, 97 patients underwent LAAC with the WATCHMAN device. All patients were discussed at a multidisciplinary meeting prior to device implantation. Longitudinal data were collected and analyzed for a composite endpoint of stroke and death at 8 months, and major bleeding at 3 and 6 months. RESULTS: Among the 90 patients included in the safety and efficacy analysis, 43 were prescribed Warfarin and 47 were prescribed NOACs. Baseline characteristics were comparable between study groups. There were no procedural complications and no significant differences in the incidence of death and stroke at 8 months or major bleeding at 3 and 6 months. CONCLUSION: For patients with AF at high risk of both thromboembolic and hemorrhagic events, NOACs as compared to Warfarin, seem to be safe and effective for short-term anticoagulation following LAAC with the WATCHMAN device. Further validation in large randomized controlled trials is required.

Intramyocardial Injection of Mesenchymal Precursor Cells and Successful Temporary Weaning From Left Ventricular Assist Device Support in Patients With Advanced Heart Failure: A Randomized Clinical Trial.

Importance: Left ventricular assist device (LVAD) therapy improves myocardial function, but few patients recover sufficiently for explant, which has focused attention on stem cells to augment cardiac recovery. Objective: To assess efficacy and adverse effects of intramyocardial injections of mesenchymal precursor cells (MPCs) during LVAD implant. Design, Setting, and Participants: A randomized phase 2 clinical trial involving patients with advanced heart failure, undergoing LVAD implant, at 19 North American centers (July 2015-August 2017). The 1-year follow-up ended August 2018. Interventions: Intramyocardial injections of 150 million allogeneic MPCs or cryoprotective medium as a sham treatment in a 2:1 ratio (n = 106 vs n = 53). Main Outcomes and Measures: The primary efficacy end point was the proportion of successful temporary weans (of 3 planned assessments) from LVAD support within 6 months of randomization. This end point was assessed using a Bayesian analysis with a predefined threshold of a posterior probability of 80% to indicate success. The 1-year primary safety end point was the incidence of intervention-related adverse events (myocarditis, myocardial rupture, neoplasm, hypersensitivity reactions, and immune sensitization). Secondary end points included readmissions and adverse events at 6 months and 1-year survival. Results: Of 159 patients (mean age, 56 years; 11.3% women), 155 (97.5%) completed 1-year of follow-up. The posterior probability that MPCs increased the likelihood of successful weaning was 69%; below the predefined threshold for success. The mean proportion of successful temporary weaning from LVAD support over 6 months was 61% in the MPC group and 58% in the control group (rate ratio [RR], 1.08; 95% CI, 0.83-1.41; P = .55). No patient experienced a primary safety end point. Of 10 prespecified secondary end points reported, 9 did not reach statistical significance. One-year mortality was not significantly different between the MPC group and the control group (14.2% vs 15.1%; hazard ratio [HR], 0.89; 95%, CI, 0.38-2.11; P = .80). The rate of serious adverse events was not significantly different between groups (70.9 vs 78.7 per 100 patient-months; difference, -7.89; 95% CI, -39.95 to 24.17; P = .63) nor was the rate of readmissions (0.68 vs 0.75 per 100 patient-months; difference, -0.07; 95% CI, -0.41 to 0.27; P = .68). Conclusions and Relevance: Among patients with advanced heart failure, intramyocardial injections of mesenchymal precursor cells, compared with injections of a cryoprotective medium as sham treatment, did not improve successful temporary weaning from left ventricular assist device support at 6 months. The findings do not support the use of intramyocardial mesenchymal stem cells to promote cardiac recovery as measured by temporary weaning from device support. Trial Registration: clinicaltrials.gov Identifier: NCT02362646.

Transapical Beating-Heart Mitral Valve Repair With an Expanded Polytetrafluoroethylene Cordal Implantation Device: Initial Clinical Experience.

BACKGROUND: Degenerative mitral valve (MV) disease is a common cause of severe mitral regurgitation (MR) and accounts for the majority of MV operations. Conventional MV surgery requires cardiopulmonary bypass, aortic cross-clamping, cardioplegia, and a thoracotomy or sternotomy and, therefore, is associated with significant disability, risks, and unpredictable rates of MV repair. Transesophageal echocardiography-guided beating-heart MV repair with expanded polytetrafluoroethylene cordal insertion has the potential to significantly reduce surgical morbidity. We report the first-in-human clinical experience with a novel preformed expanded polytetrafluoroethylene knot implantation device (Harpoon TSD-5) designed to treat degenerative MR. METHODS: Through a small left thoracotomy, the device was inserted into the heart and guided by transesophageal echocardiography to the ventricular surface of the prolapsed leaflet. Multiple expanded polytetrafluoroethylene cords were anchored in the leaflet and then adjusted to the correct length to restore MV leaflet coaptation and secured at the epicardium. RESULTS: Eleven patients with posterior leaflet prolapse and severe MR, with mean±SD age of 65±13 years and mean ejection fraction of 69±7%, were treated with 100% procedural success. Immediate postprocedural mean MR grade was trace. At 1 month, the mean MR grade was mild with significant decreases in end-diastolic volume (139 to 107 mL; P=0.03) and left atrial volume (118 to 85 mL; P=0.04). CONCLUSIONS: A novel device used for beating-heart image-guided MV repair demonstrates a significant reduction in MR with favorable left ventricular and left atrial reverse remodeling. This approach has the potential to decrease invasiveness and surgical morbidity. Further follow-up is necessary to assess long-term efficacy. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02432196.

Impact of Left Ventricular to Mitral Valve Ring Mismatch on Recurrent Ischemic Mitral Regurgitation After Ring Annuloplasty.

BACKGROUND: In ischemic mitral regurgitation (IMR), ring annuloplasty is associated with a significant rate of recurrent MR. Ring size is based on intertrigonal distance without consideration of left ventricular (LV) size. However, LV size is an important determinant of mitral valve (MV) leaflet tethering before and after repair. We aimed to determine whether LV-MV ring mismatch (mismatch of LV size relative to ring size) is associated with recurrent MR in patients with IMR after restrictive ring annuloplasty. METHODS: Patients with moderate or severe IMR from the 2 Cardiothoracic Surgical Trials Network IMR trials who received MV repair were examined at 1 year after surgery. Baseline LV size was assessed by LV end-diastolic dimension and LV end-systolic dimension (LVESd). LV-MV ring mismatch was calculated as the ratio of LV to ring size (LV end-diastolic dimension/ring size and LVESd/ring size). RESULTS: At 1 year after ring annuloplasty, 45 of 214 patients with MV repair (21%) had moderate or greater MR. In univariable logistic regression analysis, larger LVESd (P=0.02) and LVESd/ring size (P=0.007) were associated with recurrent MR. In multivariable models adjusted for age, sex, baseline LV ejection fraction, and severe IMR, only LVESd/ring size (odd ratio per 0.5 increase, 2.20; 95% confidence interval, 1.05-4.62; P=0.038) remained significantly associated with 1-year MR recurrence. CONCLUSIONS: LV-MV ring size mismatch is associated with increased risk of MR recurrence. This finding may be helpful in guiding choice of ring size to prevent recurrent MR in patients undergoing MV repair and in identifying patients who may benefit from MV repair with additional subvalvular intervention or MV replacement rather than repair alone. CLINICAL TRIAL REGISTRATION: URL:http://clinicaltrials.gov. Unique identifiers: NCT00806988 and NCT00807040.

Surgical treatment of moderate ischemic mitral regurgitation.

BACKGROUND: Ischemic mitral regurgitation is associated with increased mortality and morbidity. For surgical patients with moderate regurgitation, the benefits of adding mitral-valve repair to coronary-artery bypass grafting (CABG) are uncertain. METHODS: We randomly assigned 301 patients with moderate ischemic mitral regurgitation to CABG alone or CABG plus mitral-valve repair (combined procedure). The primary end point was the left ventricular end-systolic volume index (LVESVI), a measure of left ventricular remodeling, at 1 year. This end point was assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized as the lowest LVESVI rank. RESULTS: At 1 year, the mean LVESVI among surviving patients was 46.1±22.4 ml per square meter of body-surface area in the CABG-alone group and 49.6±31.5 ml per square meter in the combined-procedure group (mean change from baseline, -9.4 and -9.3 ml per square meter, respectively). The rate of death was 6.7% in the combined-procedure group and 7.3% in the CABG-alone group (hazard ratio with mitral-valve repair, 0.90; 95% confidence interval, 0.38 to 2.12; P=0.81). The rank-based assessment of LVESVI at 1 year (incorporating deaths) showed no significant between-group difference (z score, 0.50; P=0.61). The addition of mitral-valve repair was associated with a longer bypass time (P<0.001), a longer hospital stay after surgery (P=0.002), and more neurologic events (P=0.03). Moderate or severe mitral regurgitation was less common in the combined-procedure group than in the CABG-alone group (11.2% vs. 31.0%, P<0.001). There were no significant between-group differences in major adverse cardiac or cerebrovascular events, deaths, readmissions, functional status, or quality of life at 1 year. CONCLUSIONS: In patients with moderate ischemic mitral regurgitation, the addition of mitral-valve repair to CABG did not result in a higher degree of left ventricular reverse remodeling. Mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation but an increased number of untoward events. Thus, at 1 year, this trial did not show a clinically meaningful advantage of adding mitral-valve repair to CABG. Longer-term follow-up may determine whether the lower prevalence of mitral regurgitation translates into a net clinical benefit. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00806988.).

Mitral-valve repair versus replacement for severe ischemic mitral regurgitation.

BACKGROUND: Ischemic mitral regurgitation is associated with a substantial risk of death. Practice guidelines recommend surgery for patients with a severe form of this condition but acknowledge that the supporting evidence for repair or replacement is limited. METHODS: We randomly assigned 251 patients with severe ischemic mitral regurgitation to undergo either mitral-valve repair or chordal-sparing replacement in order to evaluate efficacy and safety. The primary end point was the left ventricular end-systolic volume index (LVESVI) at 12 months, as assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized below the lowest LVESVI rank. RESULTS: At 12 months, the mean LVESVI among surviving patients was 54.6±25.0 ml per square meter of body-surface area in the repair group and 60.7±31.5 ml per square meter in the replacement group (mean change from baseline, -6.6 and -6.8 ml per square meter, respectively). The rate of death was 14.3% in the repair group and 17.6% in the replacement group (hazard ratio with repair, 0.79; 95% confidence interval, 0.42 to 1.47; P=0.45 by the log-rank test). There was no significant between-group difference in LVESVI after adjustment for death (z score, 1.33; P=0.18). The rate of moderate or severe recurrence of mitral regurgitation at 12 months was higher in the repair group than in the replacement group (32.6% vs. 2.3%, P<0.001). There were no significant between-group differences in the rate of a composite of major adverse cardiac or cerebrovascular events, in functional status, or in quality of life at 12 months. CONCLUSIONS: We observed no significant difference in left ventricular reverse remodeling or survival at 12 months between patients who underwent mitral-valve repair and those who underwent mitral-valve replacement. Replacement provided a more durable correction of mitral regurgitation, but there was no significant between-group difference in clinical outcomes. (Funded by the National Institutes of Health and the Canadian Institutes of Health; ClinicalTrials.gov number, NCT00807040.).