Barriers to atrial fibrillation ablation during mitral valve surgery.

BACKGROUND: Nearly 40% of patients with atrial fibrillation (AF) undergoing mitral valve surgery do not receive concomitant ablation despite societal guidelines. We assessed barriers to implementation of this evidence-based practice through a survey of cardiac surgeons in 2 statewide quality collaboratives. METHODS: Adult cardiac surgeons across 2 statewide collaboratives were surveyed on their knowledge and practice regarding AF ablation. Questions concerning experience, clinical practice, case scenarios, and barriers to implementation were included. RESULTS: Among 66 respondents (66 of 135; 48.9%), the majority reported "very comfortable/frequently use" cryoablation (53 of 66; 80.3%) and radiofrequency (55 of 66; 83.3%). Only 12.1% (8/66) were not aware of the recommendations. Approximately one-half of the respondents reported learning AF ablation in fellowship (50.0%; 33 of 66) or attending courses (47.0%; 31 of 66). Responses to clinical scenarios demonstrated wide variability in practice patterns. One-half of the respondents reported no barriers; others cited increased cross-clamp time, excessive patient risk, and arrhythmia incidence as obstacles. Desired interventions included cardiology/electrophysiology support, protocols, pacemaker rate information, and education in the form of site visits, videos and proctors. CONCLUSIONS: Knowledge of evidence-based recommendations and practice patterns vary widely. These data identify several barriers to implementation of concomitant AF ablation and suggest specific interventions (mentorship/support, protocols, research, and education) to overcome these barriers.

The impact of perioperative stroke and delirium on outcomes after surgical aortic valve replacement.

OBJECTIVE: The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days. METHODS: Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7. Outcomes included 90-day functional status, neurocognitive decline from presurgical baseline, and quality of life. RESULTS: By postoperative day 7, 25 (6.6%) patients experienced clinical stroke and 103 (28.5%) manifested delirium. During index hospitalization, time to discharge was longer in patients experiencing stroke (hazard ratio, 0.62; 95% confidence interval [CI], 0.42-0.94; P = .02) and patients experiencing delirium (hazard ratio, 0.68; 95% CI, 0.54-0.86; P = .001). At day 90, patients experiencing stroke were more likely to have a modified Rankin score >2 (odds ratio [OR], 5.9; 95% CI, 1.7-20.1; P = .01), depression (OR, 5.3; 95% CI, 1.6-17.3; P = .006), a lower 12-Item Short Form Survey physical health score (adjusted mean difference -3.3 ± 1.9; P = .08), and neurocognitive decline (OR, 7.8; 95% CI, 2.3-26.4; P = .001). Delirium was associated with depression (OR, 2.2; 95% CI, 0.9-5.3; P = .08), lower 12-Item Short Form Survey physical health (adjusted mean difference -2.3 ± 1.1; P = .03), and neurocognitive decline (OR, 2.2; 95% CI, 1.2-4.0; P = .01). CONCLUSIONS: Stroke and delirium occur more frequently after SAVR than is commonly recognized, and these events are associated with disability, depression, cognitive decline, and poorer quality of life at 90 days postoperatively. These findings support the need for new interventions to reduce these events and improve patient-centered outcomes.

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.).

Pacemaker implantation associated with tricuspid repair in the setting of mitral valve surgery: Insights from a Cardiothoracic Surgical Trials Network randomized trial.

OBJECTIVES: In a recent trial, tricuspid annuloplasty (TA) during mitral valve surgery (MVS) for degenerative mitral regurgitation and moderate or less tricuspid regurgitation (TR) reduced the composite rate of death, reoperation for TR, or TR progression at 2 years. However, this benefit was counterbalanced by an increase in implantation of permanent pacemakers (PPMs). In this study, we analyzed the timing, indications, and risk factors for these implantations. METHODS: We randomized 401 patients (MVS alone = 203; MVS + TA = 198). Potential risk factors for PPMs were assessed using multivariable time-to-event models with death and PPM implantation for heart failure indications as competing risks. RESULTS: A PPM was implanted in 36 patients (9.6; 95% CI, 6.8-13.0) within 2 years of randomization, with 30/187 (16.0%) in the MVS + TA and 6/188 (3.2%) in the MVS groups (rate ratio, 5.08; 95% CI, 2.16-11.94; P < .001). Most (29/36; 80.6%) implantations occurred within 30 days postoperatively. Independent risk factors for PPM implantation within 2 years were TA (hazard ratio [HR], 5.94; 95% CI, 2.27-15.53; P < .001), increasing age (5 years, HR, 1.23; 95% CI, 1.01-1.52; P = .04), and left ventricular ejection fraction (LVEF; HR, 0.96; 95% CI, 0.92-0.99; P = .02). In the subset of TA recipients (n = 197), age (5 years, HR, 1.05; 95% CI, 1.00-1.10; P = .04) and LVEF (HR, 0.95; 95% CI, 0.91-0.99; P = .01) were associated with PPM within 2 years. CONCLUSIONS: Concomitant TA, age, and baseline LVEF were risk factors for PPM implantation in patients who underwent MVS for degenerative mitral regurgitation. Although TA was effective in preventing progression of TR, innovation is needed to identify ways to decrease PPM implantation rates.

Progression of Tricuspid Regurgitation After Surgery for Ischemic Mitral Regurgitation.

BACKGROUND: Whether to repair nonsevere tricuspid regurgitation (TR) during surgery for ischemic mitral valve regurgitation (IMR) remains uncertain. OBJECTIVES: The goal of this study was to investigate the incidence, predictors, and clinical significance of TR progression and presence of ≥moderate TR after IMR surgery. METHODS: Patients (n = 492) with untreated nonsevere TR within 2 prospectively randomized IMR trials were included. Key outcomes were TR progression (either progression by ≥2 grades, surgery for TR, or severe TR at 2 years) and presence of ≥moderate TR at 2 years. RESULTS: Patients' mean age was 66 ± 10 years (67% male), and TR distribution was 60% ≤trace, 31% mild, and 9% moderate. Among 2-year survivors, TR progression occurred in 20 (6%) of 325 patients. Baseline tricuspid annular diameter (TAD) was not predictive of TR progression. At 2 years, 37 (11%) of 323 patients had ≥moderate TR. Baseline TR grade, indexed TAD, and surgical ablation for atrial fibrillation were independent predictors of ≥moderate TR. However, TAD alone had poor discrimination (area under the curve, ≤0.65). Presence of ≥moderate TR at 2 years was higher in patients with MR recurrence (20% vs. 9%; p = 0.02) and a permanent pacemaker/defibrillator (19% vs. 9%; p = 0.01). Clinical event rates (composite of ≥1 New York Heart Association functional class increase, heart failure hospitalization, mitral valve surgery, and stroke) were higher in patients with TR progression (55% vs. 23%; p = 0.003) and ≥moderate TR at 2 years (38% vs. 22%; p = 0.04). CONCLUSIONS: After IMR surgery, progression of unrepaired nonsevere TR is uncommon. Baseline TAD is not predictive of TR progression and is poorly discriminative of ≥moderate TR at 2 years. TR progression and presence of ≥moderate TR are associated with clinical events. (Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting [CABG] Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation, NCT00806988; Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation, NCT00807040).

Risk for non-home discharge following surgery for ischemic mitral valve disease.

OBJECTIVES: To determine the frequency and risk factors for non-home discharge (NHD) and its association with clinical outcomes and quality of life (QOL) at 1 year following cardiac surgery in patients with ischemic mitral regurgitation (IMR). METHODS: Discharge disposition was evaluated in 552 patients enrolled in trials of severe or moderate IMR. Patient and in-hospital factors associated with NHD were identified using logistic regression. Subsequently, association of NHD with 1-year mortality, serious adverse events (SAEs), and QOL was assessed. RESULTS: NHD was observed in 30% (154/522) with 25% (n = 71/289) in moderate and 36% (n = 83/233) in patients with severe IMR (unadjusted P = .006), a difference not significant after including age (5-year change: adjusted odds ratio [adjOR], 1.52; 95% confidence interval [CI], 1.35-1.72; P < .001), diabetes (adjOR, 1.94; 95% CI, 1.27-2.94; P = .002), and previous heart failure (adjOR, 1.64; 95% CI, 1.06-2.52; P = .03). Odds of NHD were increased for patients with postoperative SAEs (adjOR, 1.85; 95% CI, 1.19-2.86; P = .01) but not based on type of cardiac surgery. Greater rates of death and SAEs were observed in NHD patients at 1 year: adjusted hazard ratio, 4.29 (95% CI, 2.14-8.59; P < .001) and adjusted rate ratio, 1.45 (95% CI, 1.03-2.02; P = .03), respectively. QOL did not differ significantly between groups. CONCLUSIONS: NHD is common following surgery for IMR, influenced by older age, diabetes, previous heart failure, and postoperative SAEs. These patients may be at greater risk of death and subsequent SAEs after discharge. Discussion of NHD with patients may have important implications for decision-making and guiding expectations following cardiac surgery.

Transcatheter mitral valve repair for functional mitral regurgitation: Evaluating the evidence.

OBJECTIVES: Two trials (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation Trial and Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation Trial) were published in 2018 evaluating the effectiveness and safety of transcatheter repair for patients with heart failure with significant functional mitral regurgitation, which yielded different results. This article reviews the strength of the evidence, differences in trial designs, ethical and implementation implications, and delineates future research needs to help guide the appropriate dissemination of transcatheter repair for functional patients with mitral regurgitation. METHODS: The National Heart, Lung, and Blood Institute convened a workshop of interdisciplinary experts to address these objectives. RESULTS: Transcatheter repair of functional mitral regurgitation can provide significant benefits in terms of heart failure hospitalizations, survival, and quality of life when appropriate heart failure candidates with moderate to severe or severe mitral regurgitation while on optimal guideline-directed medical therapy can be identified. Key ingredients for success are preoperative evaluation and management and postoperative care by an interdisciplinary heart team. CONCLUSIONS: Given the discordance observed between trials, ongoing innovation in patient management, and potential expansion of indications for use, the evidence base must be expanded to optimize appropriate implementation of this complex therapy. This will require more complete capture of outcome data in real-world settings for all eligible candidates whether or not they receive this therapy. Inevitably, the indications for use of this therapy will expand, as will the devices and therapeutic approaches for this population, necessitating the study of comparative effectiveness through randomized trials or observational studies. Moreover, given the substantial variations in care delivery, conducting implementation research to delineate characteristics of the optimal care model would be of benefit.

Strategies of Wait-listing for Heart Transplant vs Durable Mechanical Circulatory Support Alone for Patients With Advanced Heart Failure.

Importance: Given the shortage of donor hearts and improvement in outcomes with left ventricular assist device (LVAD) therapy, a relevant but, to date, unanswered question is whether select patients with advanced heart failure should receive LVAD destination therapy as an alternative to heart transplant. Objective: To determine whether a strategy of LVAD destination therapy is associated with similar survival benefit as wait-listing for heart transplant with or without LVAD therapy among patients with advanced heart failure. Design, Setting, and Participants: This retrospective propensity-matched cohort analysis used data on heart transplants from the United Network for Organ Sharing registry and LVAD implants from the Interagency Registry for Mechanically Assisted Circulatory Support from January 1, 2010, to December 31, 2014. The matched LVAD destination therapy cohort included 3411 patients. Data analysis for this study was conducted from December 22, 2017, to May 24, 2019. Main Outcomes and Measures: Survival at 5 years was analyzed using Cox proportional hazards models. Results: In total, 8281 patients had albumin level, creatinine level, and BMI data recorded and were included in the analysis. Despite propensity score matching, the 3411 patients receiving LVAD destination therapy still tended to be slightly older than the 3411 patients wait-listed for heart transplant (64.0 years [interquartile range, 55.0-70.0 years] vs 60.0 [interquartile range, 54.0-65.0 years]; P < .001), but there was no significant difference in sex (2701 men [79.2%] vs 2648 men [77.6%]; P = .13). After propensity score matching for age, sex, body mass index, renal function, and albumin level, 3411 patients were wait-listed for heart transplant. This included 1607 patients with bridge to transplant LVAD therapy and 1804 patients without LVAD. The strategy of wait-listing for heart transplant was associated with better 5-year survival than LVAD destination therapy (risk ratio, 0.42; 95% CI, 0.38-0.46) after matching and adjusting for key clinical factors. This survival advantage was associated with heart transplant (adjusted risk ratio for time-dependent transplant status, 0.27; 95% CI, 0.24-0.32). Conclusions and Relevance: The present analysis suggests that heart transplant with or without bridge to transplant LVAD therapy was associated with superior 5-year survival compared with LVAD destination therapy among patients matched on several relevant clinical factors. Continued improvement in LVAD technology, along with prospective comparative research, appears to be needed to amend this strategy.

Cost-effectiveness of coronary artery bypass grafting plus mitral valve repair versus coronary artery bypass grafting alone for moderate ischemic mitral regurgitation.

OBJECTIVE: The Cardiothoracic Surgical Trials Network reported that left ventricular reverse remodeling at 2 years did not differ between patients with moderate ischemic mitral regurgitation randomized to coronary artery bypass grafting plus mitral valve repair (n = 150) or coronary artery bypass grafting alone (n = 151). To address health resource use implications, we compared costs and quality-adjusted survival. METHODS: We used individual patient data from the Cardiothoracic Surgical Trials Network trial on survival, hospitalizations, quality of life, and US hospitalization costs to estimate cumulative costs and quality-adjusted life years. A microsimulation model was developed to extrapolate to 10 years. Bootstrap and deterministic sensitivity analyses were performed to address uncertainty. RESULTS: In-hospital costs were $59,745 for coronary artery bypass grafting plus mitral valve repair versus $51,326 for coronary artery bypass grafting alone (difference $8419; 95% uncertainty interval, 2259-18,757). Two-year costs were $81,263 versus $67,341 (difference 13,922 [2370 to 28,888]), and quality-adjusted life years were 1.35 versus 1.30 (difference 0.05; -0.04 to 0.14), resulting in an incremental cost-effectiveness ratio of $308,343/quality-adjusted life year for coronary artery bypass grafting plus mitral valve repair. At 10 years, its costs remained higher ($107,733 vs $88,583, difference 19,150 [-3866 to 56,826]) and quality-adjusted life years showed no difference (-0.92 to 0.87), with 5.08 versus 5.08. The likelihood that coronary artery bypass grafting plus mitral valve repair would be considered cost-effective at 10 years based on a cost-effectiveness threshold of $100K/quality-adjusted life year did not exceed 37%. Only when this procedure reduces the death rate by a relative 5% will the incremental cost-effectiveness ratio fall below $100K/quality-adjusted life year. CONCLUSIONS: The addition of mitral valve repair to coronary artery bypass grafting for patients with moderate ischemic mitral regurgitation is unlikely to be cost-effective. Only if late mortality benefits can be demonstrated will it meet commonly used cost-effectiveness criteria.

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.

Cost-Effectiveness of Mitral Valve Repair Versus Replacement for Severe Ischemic Mitral Regurgitation: A Randomized Clinical Trial From the Cardiothoracic Surgical Trials Network

BACKGROUND: The CTSN (Cardiothoracic Surgical Trials Network) recently reported no difference in left ventricular end-systolic volume index or in survival at 2 years between patients with severe ischemic mitral regurgitation (MR) randomized to mitral valve repair or replacement. However, replacement provided more durable correction of MR and fewer cardiovascular readmissions. Yet, costeffectiveness outcomes have not been addressed. METHODS AND RESULTS: We conducted a cost-effectiveness analysis of the surgical treatment of ischemic MR based on the CTSN trial (n=126 for repair; n=125 for replacement). Patient-level data on readmissions, survival, qualityof- life, and US hospital costs were used to estimate costs and quality-adjusted life years per patient over the trial duration and a 10-year time horizon. We performed microsimulation for extrapolation of outcomes beyond the 2 years of trial data. Bootstrap and deterministic sensitivity analyses were done to address parameter uncertainty. In-hospital cost estimates were $78 216 for replacement versus $72 761 for repair (difference: $5455; 95% uncertainty interval [UI]: −7784­21 193) while 2-year costs were $97 427 versus $96 261 (difference: $1166; 95% UI: −16 253­17 172), respectively. Quality-adjusted life years at 2 years were 1.18 for replacement versus 1.23 for repair (difference: −0.05; 95% UI: −0.17 to 0.07). Over 5 and 10 years, the benefits of reduction in cardiovascular readmission rates with replacement increased, and survival minimally improved compared with repair. At 5 years, cumulative costs and quality-adjusted life years showed no difference on average, but by 10 years, there was a small, uncertain benefit for replacement: $118 023 versus $119 837 (difference: −$1814; 95% UI: −27 144 to 22 602) and qualityadjusted life years: 4.06 versus 3.97 (difference: 0.09; 95% UI: −0.87 to 1.08). After 10 years, the incremental cost-effectiveness of replacement continued to improve. CONCLUSIONS: Our cost-effectiveness analysis predicts potential savings in cost and gains in quality-adjusted survival at 10 years when mitral valve replacement is compared with repair for severe ischemic MR. These projected benefits, however, were small and subject to variability. Efforts to further delineate predictors of long-term outcomes in patients with severe ischemic MR are needed to optimize surgical decisions for individual patients, which should yield more cost-effective care. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00807040.

Second annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) report: Pre-implant characteristics and outcomes.

BACKGROUND: Expanded use of pediatric ventricular assist devices (VADs) has decreased mortality in children awaiting heart transplantation. Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), a National Heart, Lung, and Blood Institute-sponsored North American database, provides a platform to understand this emerging population. METHODS: Between September 2012 and September 2016, patients aged younger than 19 years who underwent VAD implantation were enrolled in Pedimacs. FDA approved durable devices as well as temporary support devices were included. The second annual report updates the current Pedimacs data. Patients implanted with temporary devices are included in Pedimacs and this analysis includes this group of paracorporeal continuous flow VADs. RESULTS: Over the 4 years, 42 hospitals implanted 432 devices in 364 patients less than 19 yrs of age. Diagnoses included cardiomyopathy in 223 (61%), myocarditis in 41 (11%), and congenital heart disease in 77 (21%), of which 48 had single-ventricle physiology. At implant, 87% were at Intermacs patient profile 1 or 2. The age distribution of children (59% male) supported on VAD included 69 (19%) aged younger than 1 year, 66 (18%) aged 1 to 6 years, 56 (15%) aged 6 to 10 years, and 173 (48%) aged 11 to 19 years. Median follow-up was 2.2 months (range, 1 day to 41.5 months). Median (interquartile) age at implant was 1.7 (0.3-10.0) years for paracorporeal continuous-flow pumps (n = 60), 1.7 (0.4-5.3) years for paracorporeal pulsatile pumps (n = 105), and 15.0 (11.3-16.9) years for implantable continuous-flow pumps (n = 174). Support strategies included LVAD in 293 (80%), biventricular device in 55 (15%), and total artificial heart in 8 (2%). Nearly 50% of patients underwent transplantation within 6 months, with overall mortality of 19%. Adverse event burden continues to be high. CONCLUSIONS: Pedimacs constitutes the largest longitudinal pediatric VAD registry. Preimplant data across centers will be helpful at creating shared protocols with which to improve outcomes. Adverse events continue to be the major challenge, especially among the young critically ill children with complex congenital disease.

Eighth annual INTERMACS report: Special focus on framing the impact of adverse events.

BACKGROUND: The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database now includes >20,000 patients from >180 hospitals. METHODS: The eighth annual report of INTERMACS updates the first decade of patient enrollment. RESULTS: In the current era, >95% of implants are continuous flow devices. Overall survival continues to remain >80% at 1 year and 70% at 2 years. Review of major adverse events shows minimal advantage for patients with ambulatory heart failure pre-implant. Stroke, major infection, and continued inotrope requirement during the first 3 months have a major effect on subsequent survival. CONCLUSIONS: Greater application of durable devices to patients with ambulatory heart failure will mandate more effective neutralization or prevention of major adverse events.

Effect of Cerebral Embolic Protection Devices on CNS Infarction in Surgical Aortic Valve Replacement: A Randomized Clinical Trial.

Importance: Stroke is a major complication of surgical aortic valve replacement (SAVR). Objective: To determine the efficacy and adverse effects of cerebral embolic protection devices in reducing ischemic central nervous system (CNS) injury during SAVR. Design, Setting, and Participants: A randomized clinical trial of patients with calcific aortic stenosis undergoing SAVR at 18 North American centers between March 2015 and July 2016. The end of follow-up was December 2016. Interventions: Use of 1 of 2 cerebral embolic protection devices (n = 118 for suction-based extraction and n = 133 for intra-aortic filtration device) vs a standard aortic cannula (control; n = 132) at the time of SAVR. Main Outcomes and Measures: The primary end point was freedom from clinical or radiographic CNS infarction at 7 days (± 3 days) after the procedure. Secondary end points included a composite of mortality, clinical ischemic stroke, and acute kidney injury within 30 days after surgery; delirium; mortality; serious adverse events; and neurocognition. Results: Among 383 randomized patients (mean age, 73.9 years; 38.4% women; 368 [96.1%] completed the trial), the rate of freedom from CNS infarction at 7 days was 32.0% with suction-based extraction vs 33.3% with control (between-group difference, -1.3%; 95% CI, -13.8% to 11.2%) and 25.6% with intra-aortic filtration vs 32.4% with control (between-group difference, -6.9%; 95% CI, -17.9% to 4.2%). The 30-day composite end point was not significantly different between suction-based extraction and control (21.4% vs 24.2%, respectively; between-group difference, -2.8% [95% CI, -13.5% to 7.9%]) nor between intra-aortic filtration and control (33.3% vs 23.7%; between-group difference, 9.7% [95% CI, -1.2% to 20.5%]). There were no significant differences in mortality (3.4% for suction-based extraction vs 1.7% for control; and 2.3% for intra-aortic filtration vs 1.5% for control) or clinical stroke (5.1% for suction-based extraction vs 5.8% for control; and 8.3% for intra-aortic filtration vs 6.1% for control). Delirium at postoperative day 7 was 6.3% for suction-based extraction vs 15.3% for control (between-group difference, -9.1%; 95% CI, -17.1% to -1.0%) and 8.1% for intra-aortic filtration vs 15.6% for control (between-group difference, -7.4%; 95% CI, -15.5% to 0.6%). Mortality and overall serious adverse events at 90 days were not significantly different across groups. Patients in the intra-aortic filtration group vs patients in the control group experienced significantly more acute kidney injury events (14 vs 4, respectively; P = .02) and cardiac arrhythmias (57 vs 30; P = .004). Conclusions and Relevance: Among patients undergoing SAVR, cerebral embolic protection devices compared with a standard aortic cannula did not significantly reduce the risk of CNS infarction at 7 days. Potential benefits for reduction in delirium, cognition, and symptomatic stroke merit larger trials with longer follow-up. Trial Registration: clinicaltrials.gov Identifier: NCT02389894.

Pneumonia after cardiac surgery: Experience of the National Institutes of Health/Canadian Institutes of Health Research Cardiothoracic Surgical Trials Network.

RATIONALE: Pneumonia remains the most common major infection after cardiac surgery despite numerous preventive measures. OBJECTIVES: To prospectively examine the timing, pathogens, and risk factors, including modifiable management practices, for postoperative pneumonia and estimate its impact on clinical outcomes. METHODS: A total of 5158 adult cardiac surgery patients were enrolled prospectively in a cohort study across 10 centers. All infections were adjudicated by an independent committee. Competing risk models were used to assess the association of patient characteristics and management practices with pneumonia within 65 days of surgery. Mortality was assessed by Cox proportional hazards model and length of stay by a multistate model. MEASUREMENTS AND MAIN RESULTS: The cumulative incidence of pneumonia was 2.4%, 33% of which occurred after discharge. Older age, lower hemoglobin level, chronic obstructive pulmonary disease, steroid use, operative time, and left ventricular assist device/heart transplant were risk factors. Ventilation time (24-48 vs ≤24 hours; hazard ratio [HR], 2.83; 95% confidence interval [95% CI], 1.72-4.66; >48 hours HR, 4.67; 95% CI, 2.70-8.08), nasogastric tubes (HR, 1.80; 95% CI, 1.10-2.94), and each unit of blood cells transfused (HR, 1.16; 95% CI, 1.08-1.26) increased the risk of pneumonia. Prophylactic use of second-generation cephalosporins (HR, 0.66; 95% CI, 0.45-0.97) and platelet transfusions (HR, 0.49, 95% CI, 0.30-0.79) were protective. Pneumonia was associated with a marked increase in mortality (HR, 8.89; 95% CI, 5.02-15.75) and longer length of stay of 13.55 ± 1.95 days (bootstrap 95% CI, 10.31-16.58). CONCLUSIONS: Pneumonia continues to impose a major impact on the health of patients after cardiac surgery. After we adjusted for baseline risk, several specific management practices were associated with pneumonia, which offer targets for quality improvement and further research.

The NHLBI REVIVE-IT study: Understanding its discontinuation in the context of current left ventricular assist device therapy.

The National Institutes of Health National Heart, Lung, and Blood Institute convened a working group in March 2008 to discuss how therapies for heart failure (HF) might be best advanced using clinical trials involving left ventricular assist devices (LVAD). This group opined that the field was ready for a trial to assess the use of long-term ventricular assist device therapy in patients who are less ill than patients currently eligible for destination therapy, which resulted in the Randomized Evaluation of VAD InterVEntion before Inotropic Therapy (REVIVE-IT) pilot study. The specific objective of REVIVE-IT was to compare LVAD therapy with optimal medical management in patients with less advanced HF than current LVAD indications to determine if wider application of permanent LVAD use to less ill patients would be associated with improved survival, quality of life, or functional capacity. REVIVE-IT represented an extraordinary effort to provide data from a randomized clinical trial to inform clinicians, scientists, industry, and regulatory agencies about the efficacy and safety of LVAD therapy in a population with less advanced HF. Despite significant support from the medical community, industry, and governmental agencies, REVIVE-IT failed to accomplish its goal. The reasons for its failure are instructive, and the lessons learned from the REVIVE-IT experience are likely to be relevant to any future study of LVAD therapy in a population with less advanced HF.

Hybrid Coronary Revascularization for the Treatment of Multivessel Coronary Artery Disease: A Multicenter Observational Study.

BACKGROUND: Hybrid coronary revascularization (HCR) combines minimally invasive surgical coronary artery bypass grafting of the left anterior descending artery with percutaneous coronary intervention (PCI) of non-left anterior descending vessels. HCR is increasingly used to treat multivessel coronary artery disease that includes stenoses in the proximal left anterior descending artery and at least 1 other vessel, but its effectiveness has not been rigorously evaluated. OBJECTIVES: This National Institutes of Health-funded, multicenter, observational study was conducted to explore the characteristics and outcomes of patients undergoing clinically indicated HCR and multivessel PCI for hybrid-eligible coronary artery disease, to inform the design of a confirmatory comparative effectiveness trial. METHODS: Over 18 months, 200 HCR and 98 multivessel PCI patients were enrolled at 11 sites. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE) (i.e., death, stroke, myocardial infarction, repeat revascularization) within 12 months post-intervention. Cox proportional hazards models were used to model time to first MACCE event. Propensity scores were used to balance the groups. RESULTS: Mean age was 64.2 ± 11.5 years, 25.5% of patients were female, 38.6% were diabetic, and 4.7% had previous stroke. Thirty-eight percent had 3-vessel coronary artery disease, and the mean SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score was 19.7 ± 9.6. Adjusted for baseline risk, MACCE rates were similar between groups within 12 months post-intervention (hazard ratio [HR]: 1.063; p = 0.80) and during a median 17.6 months of follow-up (HR: 0.868; p = 0.53). CONCLUSIONS: These observational data from this first multicenter study of HCR suggest that there is no significant difference in MACCE rates over 12 months between patients treated with multivessel PCI or HCR, an emerging modality. A randomized trial with long-term outcomes is needed to definitively compare the effectiveness of these 2 revascularization strategies. (Hybrid Revascularization Observational Study; NCT01121263).

Rate Control versus Rhythm Control for Atrial Fibrillation after Cardiac Surgery.

BACKGROUND: Atrial fibrillation after cardiac surgery is associated with increased rates of death, complications, and hospitalizations. In patients with postoperative atrial fibrillation who are in stable condition, the best initial treatment strategy--heart-rate control or rhythm control--remains controversial. METHODS: Patients with new-onset postoperative atrial fibrillation were randomly assigned to undergo either rate control or rhythm control. The primary end point was the total number of days of hospitalization within 60 days after randomization, as assessed by the Wilcoxon rank-sum test. RESULTS: Postoperative atrial fibrillation occurred in 695 of the 2109 patients (33.0%) who were enrolled preoperatively; of these patients, 523 underwent randomization. The total numbers of hospital days in the rate-control group and the rhythm-control group were similar (median, 5.1 days and 5.0 days, respectively; P=0.76). There were no significant between-group differences in the rates of death (P=0.64) or overall serious adverse events (24.8 per 100 patient-months in the rate-control group and 26.4 per 100 patient-months in the rhythm-control group, P=0.61), including thromboembolic and bleeding events. About 25% of the patients in each group deviated from the assigned therapy, mainly because of drug ineffectiveness (in the rate-control group) or amiodarone side effects or adverse drug reactions (in the rhythm-control group). At 60 days, 93.8% of the patients in the rate-control group and 97.9% of those in the rhythm-control group had had a stable heart rhythm without atrial fibrillation for the previous 30 days (P=0.02), and 84.2% and 86.9%, respectively, had been free from atrial fibrillation from discharge to 60 days (P=0.41). CONCLUSIONS: Strategies for rate control and rhythm control to treat postoperative atrial fibrillation were associated with equal numbers of days of hospitalization, similar complication rates, and similarly low rates of persistent atrial fibrillation 60 days after onset. Neither treatment strategy showed a net clinical advantage over the other. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT02132767.).

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.).