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Background: Among patients with advanced heart failure (HF), treatment with a left ventricular assist device (LVAD) improves health-related quality of life (HRQOL). We investigated the association between psychosocial risk factors, HRQOL and outcomes after LVAD implantation., Methods: A retrospective cohort (n = 9832) of adults aged ≥ 19 years who received durable LVADs between 2008 and 2017 was identified by using the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). Patients were considered to have psychosocial risk factors if ≥ 1 of the following were present: (1) substance abuse; (2) limited social support; (3) limited cognitive understanding; (4) repeated nonadherence; and (5) major psychiatric disease. Multivariable logistic and linear regression models were used to evaluate the association between psychosocial risk factors and change in Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 scores from baseline to 1 year, persistently poor HRQOL (KCCQ-12 score < 45 at baseline and 1 year), and 1-year rehospitalization., Results: Among the final analytic cohort, 2024 (20.6%) patients had ≥ 1 psychosocial risk factors. Psychosocial risk factors were associated with a smaller improvement in KCCQ-12 scores from baseline to 1 year (mean ± SD, 29.1 ± 25.9 vs 32.6 ± 26.1; P = 0.015) for a difference of -3.51 (95% confidence interval [CI]: -5.88 to -1.13). Psychosocial risk factors were associated with persistently poor HRQOL (adjusted odds ratio [aOR] 1.35, 95% confidence interval [CI] 1.04-1.74), and 1-year all-cause readmission (adjusted hazard ratio [aHR] 1.11, 95% CI 1.05-1.18). Limited social support, major psychiatric disorder and repeated nonadherence were associated with persistently poor HRQOL, while major psychiatric disorder was associated with 1-year rehospitalization., Conclusion: The presence of psychosocial risk factors is associated with lower KCCQ-12 scores and higher risk for readmission at 1 year after LVAD implantation. These associations are statistically significant, but further research is needed to determine whether these differences are clinically meaningful., Competing Interests: Disclosures JW is supported by funding from the GA CTSA (UL1TR002378, TL1TR002382) and the National Heart, Lung and Blood Institute of the National Institutes of Health under award number 5T32HL007745. AAM is supported by funding from the American Heart Association and the Agency for Health Research and Quality (HS026081) and reports consulting fees or honoraria from Abbott, Acorai, BI Lilly, Cytokinetics, Edwards Lifesciences, Ionis, Merck and Regeneron. AKO is supported by funding from the American Heart Association. KB is supported by funding from the National Heart, Lung, and Blood Institute (NHLBI)K01HL142848, R01HL159216, R01HL160734 and funding from the Health Resources and Services Administration of the U.S. Department of Health and Human Services. All other authors report no disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Smaller body surface area (BSA) frequently precludes patients from left ventricular assist device (LVAD) therapy. We sought to investigate the clinical outcomes in patients with small BSA undergoing less invasive LVAD implantation., Methods: We conducted a retrospective review of 216 patients implanted with HeartMate 3 LVAD (Abbott, Chicago, IL) via less invasive surgery at our institution. Patients were dichotomized based on their preimplant BSA for comparison between small BSA (≤1.8 m 2 ) and normal/large BSA (>1.8 m 2 ). We analyzed patient perioperative characteristics and outcomes., Results: In our study, small BSA was found in 32 patients (14.8%), while 184 patients (85.2%) had normal/large BSA. Women were more prevalent in the small BSA group (50.0% vs 13.0%, P < 0.001). Preoperative and intraoperative data showed comparable results. Major complications and hospital length of stay did not differ by BSA group. Patients with smaller BSA had significantly decreased pump parameters at discharge, including LVAD flow (4.11 ± 0.49 vs 4.60 ± 0.54 L/min, P < 0.001) and pump speed (5,200 vs 5,400 rpm, P < 0.001). Survival to discharge and within 6 months after implantation were similar between the groups., Conclusions: Our study results suggest that less invasive HeartMate 3 implantation can be safely performed and demonstrates equivalent outcomes in patients with smaller body habitus. Randomized trials are required to confirm our data., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Igor Gosev and Dr. Himabindu Vidula are consultants for Abbott.

Background: There are limited data regarding racial disparities in outcomes after left ventricular assist device (LVAD) implantation. The purpose of this study was to compare clinical characteristics and the burden of readmissions by race among patients with LVAD., Methods: The study population included 461 patients implanted with LVADs at the University of Rochester Medical Center, NY from May 2008 to March 2020. Patients were stratified by race as White patients (N = 396 [86%]) and Black patients (N = 65 [14%]). The Anderson-Gill recurrent regression analysis was used to assess the independent association between race and the total number of admissions after LVAD implant during an average follow-up of 2.45 ± 2.30 years., Results: Black patients displayed significant differences in baseline clinical characteristics compared to White patients, including a younger age, a lower frequency of ischemic etiology, and a higher baseline serum creatinine. Black patients had a significantly higher burden of readmissions after LVAD implantation as compared with White patients 10 versus 7 (average number of hospitalizations per patient at 5 years of follow-up, respectively) translated into a significant 39% increased risk of recurrent readmissions after multivariate adjustment (Hazard ratio 1.39, 95% CI; 1.07-1.82, p 0.013)., Conclusion: Black LVAD patients experience an increased burden of readmissions compared with White patients, after adjustment for baseline differences in demographics and clinical characteristics. Future studies should assess the underlying mechanisms for this increased risk including the effect of social determinants of health on the risk of readmissions in LVAD recipients., (© 2023 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: Patients with heart failure (HF) represent a large population of patients who are at high risk for complications related to undiagnosed atrial fibrillation (AF). However, currently there are limited modalities available for early AF detection in this high-risk population. An implantable cardiac monitor (ICM) is inserted subcutaneously and can provide long-term arrhythmia information via remote monitoring., Methods and Results: Confirm-AF is a prospective randomized, nonblinded, two arm, multicenter clinical trial to be performed in the United States, enrolling 477 patients with a history of HF hospitalization and left ventricular ejection fraction >35% from 30 medical sites. Patients will be randomized in a 2:1 fashion to undergo ICM implant with remote monitoring and symptom-triggered mobile app transmissions versus (vs.) Non-ICM management and follow-up. The primary objective of this trial is to compare the time to first detection of AF lasting > 5 min using an Abbott ICM compared to non-ICM monitoring in symptomatic HF patients. This article describes the design and analytic plan for the Confirm-AF trial., Conclusions: The Confirm-AF trial seeks to accurately define the burden of AF in high-risk HF patients with LVEF > 35% using an Abbott ICM. A finding showing significantly higher incidence of AF along with improved clinical outcomes with ICM monitoring is expected to have substantial clinical implications and may change the method of monitoring high-risk HF patients., (© 2022 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Objectives: The objective of this single-center, pilot, prospective, and historical control study is to evaluate safety and feasibility outcomes associated with left atrial appendage exclusion (LAAE) concomitant with left ventricular assist device (LVAD) implantation via less invasive surgery (LIS) as a stroke prevention strategy., Methods: A predefined number of 30 eligible subjects scheduled for LIS LVAD with LAAE were enrolled in the prospective arm between January 2020 and February 2021. Eligible retrospective LIS LVAD patients without LAAE were propensity-matched in a 1:1 ratio with the prospective arm subjects. The primary study objectives were to evaluate the safety, feasibility, and efficacy of the LAAE concomitant with LIS LVAD., Results: Preoperative characteristics of patients in the Non-LAAE and LAAE groups were similar. LAAE was successfully excluded in all prospective patients (100%). Primary safety endpoints of chest tube output within the first 24 postoperative hours, Reoperation for bleeding within 48 h, and index hospitalization mortality demonstrated comparable safety of LAAE versus Non-LAAE with LIS LVAD. Cox proportional hazard regression demonstrated that LAAE with LIS LVAD was associated with 37% and 49% reduction in the risk of stroke and disabling stroke, respectively (p > .05)., Conclusion: Results from our pilot study demonstrated the safety and feasibility of LAAE concomitant with LIS LVAD as a stroke prevention strategy. This is the first prospective study describing LAAE performed concomitantly to less invasive LVAD implantation. The efficacy of LAAE in long-term stroke prevention needs to be confirmed in future prospective randomized clinical trials., (© 2022 Wiley Periodicals LLC.)

Background: Chronic cerebral hypoperfusion is a potential mechanism that causes cognitive impairment in patients with heart failure. Cognitive impairment in this population is associated with an increased mortality and poorer quality of life. Understanding the etiopathogenesis of cognitive impairment is crucial to developing effective treatment. A left ventricular assist device (LVAD) is a durable mechanical circulatory support device that restores systemic perfusion in patients with heart failure, potentially reversing cerebral hypoperfusion and cognitive impairment., Objective: This case series and systematic review examines the effect of LVAD implantation on cognition in patients with heart failure., Methods: We report a case series of 4 LVAD recipients at a tertiary academic center who underwent preimplant and postimplant cognitive testing. We also conducted a systematic review of studies with adult recipients of a continuous-flow LVAD whose cognition was measured before and after implantation. We searched Medline, EMBASE, SCOPUS, and the Cochrane library (start of database to July 16, 2021) for longitudinal, peer-reviewed studies written in English., Results: Cognitive improvement after LVAD implantation was observed in the case series, with improvement on phonemic fluency and digit symbol coding assessments. Two out of 4 cases in the case series improved on Clinical Dementia Rating: one from moderate dementia to mild cognitive impairment and another from mild cognitive impairment to unimpaired. Seven studies were included in the systematic review and were heterogeneous regarding cognitive tests employed, follow-up period, and measured outcomes. Montreal Cognitive Assessment and Trail-Making Test Part B were used most commonly. Cognitive improvement was reported in all 7 studies with at least 1 study reporting statistically significant improvements in each the following cognitive domains: delayed and immediate recall, executive function, visuospatial function, verbal function, attention, and processing speed. Most studies had small sample sizes and lacked a control group., Conclusions: LVAD implantation appears to be associated with improved cognition. Adequately powered, prospective studies are needed to examine the effect of LVAD on cognitive function in patients with heart failure. Additionally, studies that directly examine cerebral blood flow in conjunction with cognitive assessment are needed to establish the relationship between the reversal of cerebral hypoperfusion and improved cognition., (Copyright © 2022 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Right ventricular failure (RVF) remains one of the major causes of morbidity and mortality after left ventricular assist device (LVAD) implantation. We sought to compare immediate postoperative invasive hemodynamics and the risk of RVF following two different surgical approaches: less invasive surgery (LIS) versus full sternotomy (FS)., Methods: The study population comprised all 231 patients who underwent implantation of a HeartMate 3 (Abbott) LVAD at our institution from 2015 to 2020, utilizing an LIS (n = 161; 70%) versus FS (n = 70; 30%) surgical approach. Outcomes included postoperative invasive hemodynamic parameters, vasoactive-inotropic score (VIS), RVF during index hospitalization, and 6-month mortality., Results: Baseline clinical characteristics of the two groups were similar. Multivariate analysis showed that LIS, compared with FS, was associated with the improved cardiac index (CI) at the sixth postoperative hour (p = .036) and similar CI at 24 h, maintained by lower VIS at both timepoints (p = .002). The LIS versus FS approach was also associated with a three-fold lower incidence of in-hospital severe RVF (8.7% vs. 28.6%, p < .001) and need for RVAD support (5.0% vs. 17.1%, p = .003), and with 68% reduction in the risk of 6-month mortality after LVAD implantation (Hazard ratio, 0.32; CI, 0.13-0.78; p = .012)., Conclusion: Our findings suggest that LIS, compared with FS, is associated with a more favorable hemodynamic profile, as indicated by similar hemodynamic parameters maintained by lower vasoactive-inotropic support during the acute postoperative period. These findings were followed by a reduction in the risk of severe RVF and 6-month mortality in the LIS group., (© 2022 Wiley Periodicals LLC.)

It has been suggested that maintaining low mean arterial pressure (MAP) in left ventricular assist device (LVAD) recipients is associated with a reduced risk of stroke/death. However, the lower limit of the optimal MAP range has not been established. We aimed to identify this lower limit in a contemporary cohort of LVAD recipients with frequent longitudinal MAP measurements. We analyzed 86,651 MAP measurements in 309 patients with an LVAD (32% LVADs with full magnetic levitation of the impeller) at a tertiary medical center during a mean follow-up of 1.7 ± 1.1 years. Cox proportional hazards regression modeling was used to study the association of serial MAP measurements with stroke/death within 3 years after index discharge. Multivariate analysis identified MAP ≤75 mm Hg, compared with MAP >75 mm Hg, as the low MAP threshold associated with increased risk of death (hazard ratio [HR] 4.74, 95% confidence interval [CI] 2.85 to 7.87, p <0.001), stroke (HR 2.72;, 95% CI 1.39 to 5.33, p = 0.01), and stroke/death (HR 4.45, 95% CI 2.83 to 6.99, p <0.001). The risk associated with MAP ≤75 mm Hg was consistent in subgroups categorized by age, gender, race, device type, renal function, right-sided heart failure, and blood pressure medications. In conclusion, our findings suggest that maintaining MAP ≤75 mm Hg during long-term follow-up in LVAD recipients is associated with increased risk of stroke/death regardless of risk factors or medical management., Competing Interests: Disclosures Dr. Vidula has research support from Abbott Laboratories and the National Institutes of Health. Dr. Gosev is a consultant for Abbott Laboratories. Dr. Birati has research support from Medtronic. Dr. Farooq H. Sheikh has received consulting fees/honoraria and research support from Abbott Laboratories and honoraria from Medtronic. Dr. DeVore reports research funding through his institution from the American Heart Association, National Heart, Lung, and Blood Institute, and Patient-Centered Outcomes Research Institute. He has also received nonfinancial support from Abbott Laboratories for educational activities. The remaining authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

There are limited data on the association of smoking with the risk of stroke following left ventricular assist device (LVAD) implantation. We designed this study to analyze the impact of smoking status at the time of LVAD implantation on stroke. We hypothesized that current smokers are at increased risk of stroke when compared with patients who were former or never smokers. The study population comprised of 369 patients in the University of Rochester Medical Center LVAD database, implanted with an LVAD between 2008 and 2018. Patients were stratified as current smoker (smoking within 30 days before LVAD implantation), former smoker, and never smoker. Stroke was defined as a transient ischemic attack or cerebrovascular accident (hemorrhagic or ischemic). There were 45 current smokers, 198 former smokers, and 125 never smokers. Current smokers were younger (mean age 50 ± 11 years), as compared with former (58 ± 12 years) and never smokers (56 ± 13 years) p < 0.001. At 2 years following LVAD implantation, the cumulative incidence of stroke was significantly higher among current smokers (39%) as compared with former and never smokers (16% and 15%, respectively; p = 0.022 for the overall difference during follow-up). In a multivariate model adjusted for significant clinical variables, current smoking was associated with a significant 88% (p = 0.018) higher risk of stroke when compared with all noncurrent smokers. In conclusion, our data suggest that LVAD candidates who are current smokers experience a significantly higher risk of stroke following device implantation., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

Introduction: We sought to develop and implement a comprehensive enhanced recovery after surgery (ERAS) protocol for patients implanted with a left ventricular assist device (LVAD)., Methods and Results: In this article, we describe our approach to the development and phased implementation of the protocol. Additionally, we reviewed prospectively collected data for patients who underwent LVAD implantation at our institution from February 2019 to August 2020. To compare early outcomes in our patients before and after protocol implementation, we dichotomized patients into two 6-month cohorts (the pre-ERAS and ERAS cohorts) separated from each other by 6 months to allow for staff adoption of the protocol. Of the 115 LVAD implants, 38 patients were implanted in the pre-ERAS period and 46 patients in the ERAS period. Preoperatively, the patients` characteristics were similar between the cohorts. Postoperatively, we observed a decrease in bleeding (chest tube output of 1006 vs 647.5 mL, P < .001) and blood transfusions (fresh frozen plasma 31.6% vs 6.7%, P = .04; platelets 42.1% vs 8.7%, P = .001). Opioid prescription at discharge were 5-fold lower with the ERAS approach (P < .01). Furthermore, the number of patients discharged to a rehabilitation facility decreased significantly (20.0% vs 2.4%, P = .02). The index hospitalization length of stay and survival were similar between the groups., Conclusions: ERAS for patients undergoing LVAD implantation is a novel, evidence-based, interdisciplinary approach to care with multiple potential benefits. In this article, we describe the details of the protocol and early positive changes in clinical outcomes. Further studies are needed to evaluate benefits of an ERAS protocol in an LVAD population.Lay Summary: Enhanced recovery after surgery (ERAS) is the implementation of standardized clinical pathways that ensures the use of best practices and decreased variation in perioperative care. Multidisciplinary teams work together on ERAS, thereby enhancing communication among health care silos. ERAS has been used for more than 30 years by other surgical services and has been shown to lead to a decreased length of stay, fewer complications, lower mortality, fewer readmissions, greater job satisfaction, and lower costs. Our goal was to translate these benefits to the perioperative care of complex patients with a left ventricular assist device. Early results suggest that this goal is possible; we have observed a decrease in transfusions, discharge on opioids, and discharge to a rehabilitation facility., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Historically, obesity was considered a relative contraindication to left ventricular assist device (LVAD) implantation with less invasive surgery (LIS). The present study aimed to compare the outcomes of obese patients who underwent LVAD implantation through LIS with those who received full sternotomy (FS) implantation., Methods: We retrospectively reviewed all patients implanted with HeartMate 3 LVAD in our institution between September 2015 and June 2020. Obese patients (BMI ≥ 30 kg/m 2 ) were included and dichotomized based on surgical approach into the FS or LIS cohort., Results: Of 231 implanted patients, 107 (46%) were obese and included in the study. FS was performed in 26 (24%) patients and LIS approach in 81 (76%) patients. Preoperative patient characteristics were similar between the cohorts. Postoperatively, patients in LIS cohort had less bleeding (p = 0.029), fewer transfusions (p = 0.042), shorter duration of inotropic support (p = 0.049), and decreased incidence of severe RV failure (11.1% vs 30.8%, p = 0.028). Survival to discharge for the obese population was 87.5% overall and did not differ based on an approach (91.4% LIS vs 76.9% FS, p = 0.079). More LIS patients were discharged home (60.0% vs 82.4%, p = 0.041) rather than to rehabilitation center., Conclusion: Our results showed that the LIS approach in obese patients is associated with fewer postoperative complications and a trend towards better short-term survival. These results suggest that less invasive LVAD implantation is a safe and effective approach for obese patients. Future prospective randomized trials are required to substantiate these results., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

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Background: Peripartum cardiomyopathy (PPCM) occurs in ≈1:2000 deliveries in the United States and worldwide. The genetic underpinnings of PPCM remain poorly defined. Approximately 10% of women with PPCM harbor truncating variants in TTN (TTNtvs). Whether mutations in other genes can predispose to PPCM is not known. It is also not known if the presence of TTNtvs predicts clinical presentation or outcomes. Nor is it known if the prevalence of TTNtvs differs in women with PPCM and preeclampsia, the strongest risk factor for PPCM., Methods: Women with PPCM were retrospectively identified from several US and international academic centers, and clinical information and DNA samples were acquired. Next-generation sequencing was performed on 67 genes, including TTN , and evaluated for burden of truncating and missense variants. The impact of TTNtvs on the severity of clinical presentation, and on clinical outcomes, was evaluated., Results: Four hundred sixty-nine women met inclusion criteria. Of the women with PPCM, 10.4% bore TTNtvs (odds ratio=9.4 compared with 1.2% in the reference population; Bonferroni-corrected P [ P *]=1.2×10 -46 ). We additionally identified overrepresentation of truncating variants in FLNC (odds ratio=24.8, P *=7.0×10 -8 ), DSP (odds ratio=14.9, P *=1.0×10 -8 ), and BAG3 (odds ratio=53.1, P *=0.02), genes not previously associated with PPCM. This profile is highly similar to that found in nonischemic dilated cardiomyopathy. Women with TTNtvs had lower left ventricular ejection fraction on presentation than did women without TTNtvs (23.5% versus 29%, P =2.5×10 -4 ), but did not differ significantly in timing of presentation after delivery, in prevalence of preeclampsia, or in rates of clinical recovery., Conclusions: This study provides the first extensive genetic and phenotypic landscape of PPCM and demonstrates that predisposition to heart failure is an important risk factor for PPCM. The work reveals a degree of genetic similarity between PPCM and dilated cardiomyopathy, suggesting that gene-specific therapeutic approaches being developed for dilated cardiomyopathy may also apply to PPCM, and that approaches to genetic testing in PPCM should mirror those taken in dilated cardiomyopathy. Last, the clarification of genotype/phenotype associations has important implications for genetic counseling.

Background: Studies of long-term inotrope use in advanced HF have previously provided limited and conflicting results. This study aimed to evaluate the safety and efficacy of long-term milrinone use and identify predictors of failure to bridge to orthotropic heart transplant (OHT) in a cohort of end-stage heart failure (HF) patients listed for heart transplantation and receiving inotrope therapy., Methods: The study included 150 adults listed for OHT at a single center from 2001 to 2017 who received milrinone therapy for ≥30 days. Multivariate Cox proportional hazards models were used to identify factors associated with "failure" (left ventricular assist device, intra-aortic balloon pump, status downgrade due to instability, death) vs. "success" (OHT, recovery) during bridging to OHT., Results: "Failure" occurred in 33 (22%) patients. Factors independently associated with failure included male sex (HR = 7.6; p = 0.004), no implantable cardioverter-defibrillator (HR = 3.8; p = 0.009), and lack of guideline-directed medical therapy (GDMT) with a beta-blocker (HR = 7.8; p = 0.002) or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (HR = 6.3; p < 0.001). Patients who received fewer guideline-directed medications had a higher cumulative probability of failure. Adverse events included central line-associated bloodstream infection (2.55 per 1000 line-days) and arrhythmia (1.59 per 1000 treatment-days)., Conclusions: Our findings suggest that long-term milrinone therapy in selected patients is associated with a high rate of successful bridging to OHT and a low rate of adverse events. Patients intolerant of GDMT are more likely to fail to bridge to OHT without mechanical support. Sex differences in outcomes associated with milrinone therapy should be explored., Competing Interests: Declaration of competing interest JTB receives research support from University of Rochester CTSA award number UL1 TR002001 from the National Center for Advancing Translational Sciences of the National Institutes of Health, and serves in an advisory role for AvantGarde Health. There is nothing to disclose for the other authors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Data on the clinical significance of early hospital readmission within 90 days following left ventricular assist device (LVAD) implantation in patients with continuous-flow LVAD are limited. We aimed to assess the incidence, predictors, and outcomes of 90-day readmission in LVAD patients. Hospital readmission or death was assessed within 90 days after hospital discharge in 177 patients with HeartMate II LVADs implanted between May 2008 and June 2014. Predictors of early readmission and risk of death were evaluated using multivariable Cox models following adjustment for clinical covariates. Hospital readmission or death rate was 37% within 90 days. Age at implantation (hazard ratio [HR] = 1.03 per 1 year increase, p = 0.016), diabetes (HR = 2.19, p = 0.031) and smoking at baseline (HR = 2.06, p = 0.034) predicted early hospital readmission, while a higher baseline body mass index was found to be protective (HR = 0.92 per each unit increase in body mass index, p = 0.003). One-year all-cause mortality was 19% in patients with early hospital readmission as compared to 1% with no early hospital readmission (HR 15.50, p = 0.01). One-year mortality was 35% in patients with 2 or more readmissions compared to 10% mortality in patients with one readmission and 1% mortality in patients with no readmissions (p < 0.001). In LVAD patients, there is a high incidence of hospital readmission within 90 days, which is associated with an increased mortality. Targeted interventions, such as closer follow-up to prevent early and recurrent hospital readmissions in LVAD recipients, are warranted to improve outcomes.

As median survival for left ventricular assist device (LVAD) patients increases, the incidence of adverse events requiring device exchange is likely to increase as well. Less invasive surgical approaches for device exchange of older generation pumps have demonstrated multiple potential benefits compared with median sternotomy. However, there remains a paucity of data in regard to less invasive surgical techniques for the exchange of the newest generation intrapericardial devices. In this report we describe a complete sternal-sparing technique for the LVAD exchange of a HeartMate 3 via bilateral minithoracotomies., (© 2020 Wiley Periodicals, Inc.)

Background and study aims  Left ventricular assist device (LVAD) placement is a therapeutic modality for patients with end-stage heart failure. Gastrointestinal bleeding is a common complication following LVAD implantation. The aim of this study was to report our experience in management and outcomes of gastrointestinal bleeding in a large cohort of patients with LVADs. Patients and methods  We performed a retrospective review of all patients who underwent LVAD implantation at the University of Rochester Medical Center from January 2008 to June 2017. Data were collected on patient characteristics, clinical aspects of gastrointestinal bleeding events, and procedural interventions. A Cox proportional hazard model was utilized to identify potential risk factors for a gastrointestinal bleeding event. Results  During the study period, 345 patients underwent LVAD implantation. Of these, 125 patients (36.2 %) experienced 297 gastrointestinal bleeding events resulting in 533 endoscopic procedures. The diagnostic yield of endoscopy in determining a bleeding source was 49.5 %. If required, therapeutic interventions were successful in achieving homeostasis in 96.2 % of procedures. Our 30-day overall post-procedure adverse event (AE) rate was 6.6 %. Procedure-related (bleeding, infection, and perforation) AEs were very minimal (2.8 %). A Cox proportional hazard model indicated that older age at implant, female sex, African-American race, diabetes mellitus, and pulmonary hypertension were statistically significant predictors of a gastrointestinal bleeding event following LVAD implantation. Conclusions  LVAD patients have a high risk of gastrointestinal bleeding. Endoscopy was able to safely locate a bleeding lesion in approximately half of our patients and was successful in treating bleeding lesions in a majority of the cases., Competing Interests: Competing interests The authors declare that they have no conflict of interest.

Background: Left ventricular assist devices (LVADs) have improved outcomes for selected patients with advanced heart failure, but alternative optimal surgical techniques remain to be defined. We aim to describe our initial experience in using a sternal-sparing (SS) technique for implantation of a magnetically levitated LVAD, the HeartMate 3 (HM3) pump., Methods: This retrospective, single-center study included consecutive patients implanted with the HM3 LVAD between September 2015 and September 2018. Patients were compared based on surgical approach: SS or traditional sternotomy (TS). The primary outcome was overall survival at 6 months. Secondary outcomes included peri-operative complications, blood product utilization, and hospital readmissions., Results: Of 105 patients implanted with the HM3 LVAD, 41 (39%) were implanted via SS and 64 (61%) via TS approach. There were no intraoperative conversions. The SS patients were younger; otherwise, all other characteristics were similar between cohorts. The SS cohort demonstrated a significantly lower incidence of severe right ventricular failure (7% vs 28%, p = 0.012), fewer blood-product transfusions (41% vs 86%, p < 0.001), and shorter index hospital length of stay (15.5 vs 21 days, p = 0.018). Six-month survival was 93% for the SS cohort., Conclusions: In this single-center observational study, we have demonstrated that the SS approach may be a safe and effective surgical technique for implantation of the HM3 LVAD in well-selected patients. The potential benefits compared with TS require further inquiry., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular assist device (LVAD) therapy has been the standard of care for selected patients with advance heart failure. Even though considerable strides have been achieved with the introduction of the newest centrifugal pump, therapy is still burdened with significant perioperative complications. Smaller devices, along with improved techniques and instruments, have encouraged the adoption of minimally invasive cardiac surgery (MICS) techniques for LVAD implantation to improve perioperative outcomes., Methods: We describe a technique for complete sternal-sparing (CSS) HeartMate 3 (Abbott Laboratories, Abbott Park, IL) left ventricular assist device (LVAD) implantation using bilateral thoracotomies and discuss early clinical outcomes of the first ten consecutive patients who underwent CSS implantation of the HeartMate 3 LVAD at our institution., Results: The median length of stay in the intensive care unit was 3.5 days. No patients required reexploration for postoperative bleeding. There was no incidence of right ventricle failure, stroke, renal failure, hepatic failure, or myocardial infarction. The median length of hospitalization after LVAD implantation was 14.5 days (interquartile range, 12 to 17 days)., Conclusions: Our early outcomes suggest that the CSS approach may reduce the incidence of right ventricular failure, bleeding, intubation time, and intensive care unit length of stay. Further studies are needed to fully elucidate the advantages of CSS LVAD implantation compared with median sternotomy., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Exercise and heart disease both induce cardiac remodeling, but only disease causes fibrosis and compromises heart function. The cardioprotective benefits of exercise have been attributed to changes in cardiomyocyte physiology, but the impact of exercise on cardiac fibroblasts (CFs) is unknown. Here, RNA-sequencing reveals rapid divergence of CF transcriptional programs during exercise and disease. Among the differentially expressed programs, NRF2-dependent antioxidant genes - including metallothioneins (Mt1 and Mt2) - are induced in CFs during exercise and suppressed by TGF-β/p38 signaling in disease. In vivo, mice lacking Mt1/2 exhibit signs of cardiac dysfunction in exercise, including cardiac fibrosis, vascular rarefaction, and functional decline. Mechanistically, exogenous MTs derived from fibroblasts are taken up by cultured cardiomyocytes, reducing oxidative damage-dependent cell death. Importantly, suppression of MT expression is conserved in human heart failure. Taken together, this study defines the acute transcriptional response of CFs to exercise and disease and reveals a cardioprotective mechanism that is lost in disease.

The association of an implantable cardioverter defibrillator (ICD) with survival in patients with left ventricular assist devices (LVADs) is not well understood. We evaluated all-cause mortality by the presence of an ICD at the time of LVAD implantation, or by ICD implantation after LVAD placement in 191 patients, using Kaplan-Meier survival analyses and Cox models with multivariate adjustment. During the median follow-up of 23 months, 33 of 129 patients (26%) with an ICD and 17 of 62 patients (27%) without an ICD died. Patients had similar all-cause mortality with or without an ICD before LVAD, after censoring for post-LVAD ICD implantation (log-rank p = 0.889). Multivariate models after adjustments revealed no statistically significant survival benefit from an ICD before LVAD (hazard ratio [HR]: 0.65, 95% CI: 0.27-1.57, p = 0.340). Thirty-one of 62 (50%) patients without an ICD before LVAD implantation subsequently received an ICD after LVAD, although these patients did not have significantly better survival when compared with those with no ICD in a time-dependent analysis (HR: 0.70, 95% CI: 0.25-1.95, p = 0.497). Among LVAD patients, neither a previously implanted ICD nor a new ICD implantation after LVAD yielded statistically significant survival benefit. Further studies are warranted to investigate the role of ICD implantation in LVAD patients.

Background: Hypertrophic cardiomyocyte growth and dysfunction accompany various forms of heart disease. The mechanisms responsible for transcriptional changes that affect cardiac physiology and the transition to heart failure are not well understood. The intercalated disc (ID) is a specialized intercellular junction coupling cardiomyocyte force transmission and propagation of electrical activity. The ID is gaining attention as a mechanosensitive signaling hub and hotspot for causative mutations in cardiomyopathy., Methods: Transmission electron microscopy, confocal microscopy, and single-molecule localization microscopy were used to examine changes in ID structure and protein localization in the murine and human heart. We conducted detailed cardiac functional assessment and transcriptional profiling of mice lacking myocardin-related transcription factor (MRTF)-A and MRTF-B specifically in adult cardiomyocytes to evaluate the role of mechanosensitive regulation of gene expression in load-induced ventricular remodeling., Results: We found that MRTFs localize to IDs in the healthy human heart and accumulate in the nucleus in heart failure. Although mice lacking MRTFs in adult cardiomyocytes display normal cardiac physiology at baseline, pressure overload leads to rapid heart failure characterized by sarcomere disarray, ID disintegration, chamber dilation and wall thinning, cardiac functional decline, and partially penetrant acute lethality. Transcriptional profiling reveals a program of actin cytoskeleton and cardiomyocyte adhesion genes driven by MRTFs during pressure overload. Indeed, conspicuous remodeling of gap junctions at IDs identified by single-molecule localization microscopy may partially stem from a reduction in Mapre1 expression, which we show is a direct mechanosensitive MRTF target., Conclusions: Our study describes a novel paradigm in which MRTFs control an acute mechanosensitive signaling circuit that coordinates cross-talk between the actin and microtubule cytoskeleton and maintains ID integrity and cardiomyocyte homeostasis in heart disease.

Importance: The prevalence of nonischemic dilated cardiomyopathy (DCM) is greater in individuals of African ancestry than in individuals of European ancestry. However, little is known about whether the difference in prevalence or outcomes is associated with functional genetic variants., Objective: We hypothesized that Bcl2-associated anthanogene 3 (BAG3) genetic variants were associated with outcomes in individuals of African ancestry with DCM., Design: This multicohort study of the BAG3 genotype in patients of African ancestry with dilated cardiomyopathy uses DNA obtained from African American individuals enrolled in 3 clinical studies: the Genetic Risk Assessment of African Americans With Heart Failure (GRAHF) study; the Intervention in Myocarditis and Acute Cardiomyopathy Trial-2 (IMAC-2) study; and the Genetic Risk Assessment of Cardiac Events (GRACE) study. Samples of DNA were also acquired from the left ventricular myocardium of patients of African ancestry who underwent heart transplant at the University of Colorado and University of Pittsburgh., Main Outcomes and Measures: The primary end points were the prevalence of BAG3 mutations in African American individuals and event-free survival in participants harboring functional BAG3 mutations., Results: Four BAG3 genetic variants were identified; these were expressed in 42 of 402 African American individuals (10.4%) with nonischemic heart failure and 9 of 107 African American individuals (8.4%) with ischemic heart failure but were not present in a reference population of European ancestry (P < .001). The variants included 2 nonsynonymous single-nucleotide variants; 1 three-nucleotide in-frame insertion; and 2 single-nucleotide variants that were linked in cis. The presence of BAG3 variants was associated with a nearly 2-fold (hazard ratio, 1.97 [95% CI, 1.19-3.24]; P = .01) increase in cardiac events in carriers compared with noncarriers. Transfection of transformed adult human ventricular myocytes with plasmids expressing the 4 variants demonstrated that each variant caused an increase in apoptosis and a decrease in autophagy when samples were subjected to the stress of hypoxia-reoxygenation., Conclusions and Relevance: This study demonstrates that genetic variants in BAG3 found almost exclusively in individuals of African ancestry were not causative of disease but were associated with a negative outcome in patients with a dilated cardiomyopathy through modulation of the function of BAG3. The results emphasize the importance of biological differences in causing phenotypic variance across diverse patient populations, the need to include diverse populations in genetic cohorts, and the importance of determining the pathogenicity of genetic variants.

As more patients are supported for longer periods by a left ventricular assist device (LVAD), hospital readmission is becoming a growing problem. However, data about temporal changes in readmission rates and causes for patients with prolonged LVAD support are limited. We aimed to evaluate rates, causes, and predictors of any and long-term readmission after LVAD placement at our institution. We followed 177 HeartMate II LVAD patients for a mean of 1.90 ± 1.33 years post initial discharge after implantation. A marginal rate model was used to evaluate readmission rates, accounting for mortality. During the first year, the readmission rate was 1.79 (95% confidence interval 1.51 to 2.10) readmissions per year. The readmission rate was 1.54 (95% confidence interval 1.07 to 1.93) 2 to 3 years after initial discharge. There was a further decrease in readmission rate in the 3- to 4-year interval. The most common causes of readmission during the first year and even after 3 to 4 years of LVAD support were bleeding (excluding intracranial bleeding) and infection. Female gender was associated with an increased risk of readmission in multivariable analyses, while blood urea nitrogen was predictive of long-term readmissions. In conclusion, readmission after LVAD implantation is common, but readmission rates decrease during long-term follow-up. Bleeding and infection remain leading causes of readmission during longer follow-up and strategies to decrease these complications may reduce readmission rates. Female patients and patients with renal dysfunction have increased risk of readmission and further studies are needed to improve outcomes in these groups., (Copyright © 2018. Published by Elsevier Inc.)

Background: Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain a challenging problem in patients with implantable cardioverter-defibrillators (ICDs)., Objectives: This study aimed to determine whether ranolazine administration decreases the likelihood of VT, VF, or death in patients with an ICD., Methods: This was double-blind, placebo-controlled clinical trial in which high-risk ICD patients with ischemic or nonischemic cardiomyopathy were randomized to 1,000 mg ranolazine twice a day or placebo. The primary endpoint was VT or VF requiring appropriate ICD therapy or death, whichever occurred first. Pre-specified secondary endpoints included ICD shock for VT, VF, or death and recurrent VT or VF requiring ICD therapy., Results: Among 1,012 ICD patients (510 randomized to ranolazine and 502 to placebo) the mean age was 64 ± 10 years and 18% were women. During 28 ± 16 months of follow-up there were 372 (37%) patients with primary endpoint, 270 (27%) patients with VT or VF, and 148 (15%) deaths. The blinded study drug was discontinued in 199 (39.6%) patients receiving placebo and in 253 (49.6%) patients receiving ranolazine (p = 0.001). The hazard ratio for ranolazine versus placebo was 0.84 (95% confidence interval: 0.67 to 1.05; p = 0.117) for VT, VF, or death. In a pre-specified secondary analysis, patients randomized to ranolazine had a marginally significant lower risk of ICD therapies for recurrent VT or VF (hazard ratio: 0.70; 95% confidence interval: 0.51 to 0.96; p = 0.028). There were no other significant treatment effects in other pre-specified secondary analyses, which included individual components of the primary endpoint, inappropriate shocks, cardiac hospitalizations, and quality of life., Conclusions: In high-risk ICD patients, treatment with ranolazine did not significantly reduce the incidence of the first VT or VF, or death. However, the study was underpowered to detect a difference in the primary endpoint. In prespecified secondary endpoint analyses, ranolazine administration was associated with a significant reduction in recurrent VT or VF requiring ICD therapy without evidence for increased mortality. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253)., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Despite previous studies, the mortality risk of patients with diabetes mellitus after left ventricular assist device (LVAD) implant remains unclear. In addition, the relationship between the degree of glycemic control and long-term mortality risk in LVAD patients with diabetes has not been established., Methods: Ninety-five nondiabetic patients and 96 diabetic patients from the University of Rochester Medical Center who received a HeartMate II (Thoratec, Pleasanton, CA) continuous-flow LVAD between May 2008 and June 2014 were included in this study. The primary outcome was all-cause mortality. Secondary outcomes included rates of infection, neurologic dysfunction, renal dysfunction, and rehospitalization. Kaplan-Meier survival analyses and Cox models were utilized., Results: During follow-up, 32 diabetic patients (33%) and 15 nondiabetic patients (16%) died after LVAD implantation. Cumulative probability of death was higher for diabetic patients when compared with nondiabetic patients (42% versus 21% at 3 years, p = 0.013). There were no significant differences in overall rates of infection, neurologic dysfunction, and rehospitalization between the two groups. However, after an initial secondary outcome event, diabetic patients continued to have a higher mortality rate when compared with nondiabetic patients. There was no statistically significant difference in the risk of death between diabetic patients with pre-LVAD hemoglobin A1c less than 7.0% and diabetic patients with pre-LVAD hemoglobin A1c 7.0% or greater (hazard ratio 1.71, 95% confidence interval: 0.72 to 4.08, p = 0.223)., Conclusions: Diabetic patients who underwent LVAD implantation had a higher risk of death compared with nondiabetic patients. Adverse event rates did not differ between the two groups. Finally, the degree of glycemic control in diabetic patients before LVAD was not found to influence mortality., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Bleeding is a major cause of morbidity in patients with continuous flow left ventricular assist devices (LVADs). We sought to identify clinical predictors of bleeding within the first year of LVAD implantation., Methods: A prospective study was performed on 30 patients with HeartMate II implantation at the University of Rochester Medical Center, Rochester, New York, United States. Blood was collected within 1 week before implantation, and at 1, 3, and 30 ± 10 days after implantation. Blood samples were analyzed for prothrombin time (PT), international normalized ratio (INR), von Willebrand factor (vWF) activity, vWF antigen, vWF multimers, collagen binding assay, factor VIII, and epinephrine closure time. The first bleeding event within 1 year of implantation was recorded., Results: There were 17 (57%) patients with a bleeding event. The cumulative incidence of bleeding was 50% at 304 days. Age at the time of LVAD implantation was associated with higher risk of bleeding (hazard ratio (HR) = 1.05, 95% confidence interval (CI) = 1.01-1.10, p = 0.013). Higher baseline INR was also associated with increased risk of bleeding after adjusting for age at the time of implant (HR = 6.58, 95% CI = 1.21-35.70, p = 0.028). The bleeders and non-bleeders had similar hemostatic markers at all four time points. Prior to LVAD, mean epinephrine closure time was similar between bleeders and non-bleeders. However, post LVAD measurement of epinephrine, closure time was frequently limited by platelet clumping., Conclusion: Older age and baseline INR are associated with higher risk of bleeding in LVAD patients. Platelet clumping may suggest underlying platelet dysfunction and associated high risk of bleeding.

Heart disease is associated with the accumulation of resident cardiac fibroblasts (CFs) that secrete extracellular matrix (ECM), leading to the development of pathological fibrosis and heart failure. However, the mechanisms underlying resident CF proliferation remain poorly defined. Here, we report that small proline-rich protein 2b ( Sprr2b ) is among the most up-regulated genes in CFs during heart disease. We demonstrate that SPRR2B is a regulatory subunit of the USP7/MDM2-containing ubiquitination complex. SPRR2B stimulates the accumulation of MDM2 and the degradation of p53, thus facilitating the proliferation of pathological CFs. Furthermore, SPRR2B phosphorylation by nonreceptor tyrosine kinases in response to TGF-β1 signaling and free-radical production potentiates SPRR2B activity and cell cycle progression. Knockdown of the Sprr2b gene or inhibition of SPRR2B phosphorylation attenuates USP7/MDM2 binding and p53 degradation, leading to CF cell cycle arrest. Importantly, SPRR2B expression is elevated in cardiac tissue from human heart failure patients and correlates with the proliferative state of patient-derived CFs in a process that is reversed by insulin growth factor-1 signaling. These data establish SPRR2B as a unique component of the USP7/MDM2 ubiquitination complex that drives p53 degradation, CF accumulation, and the development of pathological cardiac fibrosis., Competing Interests: Conflict of interest statement: E.M.S. is the recipient of a research grant from Novartis Pharmaceuticals.

Limited data assessing the clinical significance of post-left ventricular assist device (LVAD) in renal function are available. We aimed to investigate the impact of changes in renal function after LVAD implantation on subsequent long-term outcomes. We followed 184 patients with HeartMate II LVADs implanted between May 2008 and November 2014. Serial assessment of renal function, was performed at baseline and at day 1, day 7, 1 month, 3 months, 6 months, 1 year, and 2 years after implantation. Effects of 1-month GFR and changes in GFR from baseline to 1 month on long-term mortality and hospital re-admission were evaluated. There were 30 patients with GFR <45 (low), 44 with GFR 45 to 59 (intermediate), and 110 with GFR ≥60 (normal) at baseline. Only patients with baseline GFR <45 experienced significant improvement in GFR after 2 years of follow-up (p = 0.012). At 1 month, a higher GFR category was significantly associated with a 31% reduction in mortality (hazard ratio [HR] 0.69, CI 0.49 to 0.98, p = 0.036), but not re-admission. Patients with baseline low and intermediate GFR who had no improvement in renal function category at 1 month experienced significantly greater risk of mortality (HR 1.95, CI 1.10 to 3.43, p = 0.022) and re-admission (HR 1.75, CI 1.07 to 2.84, p = 0.025), relative to patients whose GFR was normal at baseline and 1 month. In conclusion, renal function after LVAD implantation improves in patients with GFR <45. Change in renal function from baseline to 1 month after implantation is a powerful marker of long-term outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Left ventricular assist device (LVAD) exit-site infections represent a major challenge in the era of modern LVADs. Infections caused by Pseudomonas are particularly difficult to treat due to limited antibiotic susceptibility. We hypothesized that keeping the LVAD exit site dry while bathing could result in reduced incidence of Pseudomonas infections., Methods: Starting in April 2013, all patients who underwent placement of HeartMate II (HM II) LVAD were instructed not to take conventional showers and to keep the exit site dry while bathing. We retrospectively reviewed patients who underwent HeartMate II LVAD implantation at our institution. Overall and Pseudomonas exit-site infections were compared between two groups: Group 1 was implanted with an LVAD prior to intervention (4/1/2013) and Group 2 after the intervention. Both groups were subjected to cumulative hazard analysis and compared using log-rank test., Results: From November 2006 to September 2015, 283 patients underwent HM II LVAD placement at a single institution (Group 1, 163 patients; Group 2, 120 patients). Median age was 59 years (interquartile range [IQR] 50-65), and 57 (20%) were female. Overall, driveline infection was noted in 86 (30%) patients. Pseudomonas was the causative or coexisting organism in 16 (6%) patients. Median days to infection were 347 (IQR, 162-568). Driveline infection was identified in 69 (42%) patients in Group 1 and 17 (14 %) in Group 2. Pseudomonas was an infectious organism in 15 (9%) patients of Group 1 and one (1%) patient of Group 2. The incidence of Pseudomonas exit-site infections (p = 0.077) decreased substantially after the intervention., Conclusions: Stopping conventional showering may reduce the rate of Pseudomonas LVAD exit-site infections. Additional, multi-institutional data are needed to further evaluate these findings.

Background: In peripartum cardiomyopathy, the prevalence of focal myocardial damage detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance is important to elucidate mechanisms of myocardial injury and cardiac dysfunction. LGE equates irreversible myocardial injury, but LGE prevalence in peripartum cardiomyopathy is uncertain., Methods and Results: Among 100 women enrolled within the Investigations of Pregnancy Associated Cardiomyopathy cohort, we recruited 40 women at 13 centers to undergo LGE cardiovascular magnetic resonance, enrolled within the first 13 weeks postpartum. Follow-up scans occurred at 6 months postpartum, and death/transplant rates at 12 months. Baseline characteristics did not differ significantly in the parent cohort according to cardiovascular magnetic resonance enrollment except for mechanical circulatory support. LGE was noted only in 2 women (5%) at baseline. While left ventricular dysfunction with enlargement was prevalent at baseline cardiovascular magnetic resonance scans (eg, ejection fraction 38% [Q1-Q3 31-50%], end diastolic volume index=108 mL/m 2 [Q1-Q3 83-134 mL/m 2 ]), most women demonstrated significant improvements at 6 months, consistent with a low prevalence of LGE. LGE was not related to baseline clinical variables, ejection fraction, New York Heart Association heart failure class, or mortality. Neither of the 2 women who died exhibited LGE. LGE was inversely associated with persistent left ventricular ejection fraction at 6 months ( P =0.006)., Conclusions: Factors other than focal myocardial damage detectable by LGE explain the initial transient depressions in baseline left ventricular ejection fraction, yet focal myocardial damage may contribute to persistent myocardial dysfunction and hinder recovery in a small minority. Most women exhibit favorable changes in ventricular function over 6 months., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01085955., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Among various cardiac autoantibodies (AAbs), those recognizing the β 1 -adrenergic receptor (β 1 AR) demonstrate agonist-like effects and induce myocardial damage that can be reversed by β-blockers and immunoglobulin G3 (IgG3) immunoadsorption., Objectives: The goal of this study was to investigate the role of β 1 AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy., Methods: Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction [LVEF] ≤0.40; <6 months). The presence of IgG and IgG3-β 1 AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months., Results: Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-β 1 AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p < 0.01; left ventricular end-systolic diameter, p = 0.03). At 6 months, LVEF was significantly higher in the IgG3 group (p = 0.007). Multiple regression analysis showed that IgG3-β 1 AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, β = 0.20, p = 0.01; change in LVEF, β = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint., Conclusions: IgG3-β 1 AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Previous studies have shown that women with continuous-flow left ventricular assist devices (LVADs) are at greater risk of neurologic events. However, the relation between neurologic events and subsequent outcomes by gender is not well understood. We aimed to identify gender differences in the risk of neurologic events in patients with LVAD and the impact of time-dependent neurologic event on all-cause mortality by gender. Our study included 34 women and 157 men who received a HeartMate II LVAD at the University of Rochester Medical Center, Rochester, New York, from May 5, 2008, to June 5, 2014. Neurologic event was defined as a transient ischemic attack or cerebrovascular accident (hemorrhagic or ischemic). During a median follow-up of 25 months, 16 women (47%) and 20 men (13%) had neurologic events. Among patients with neurologic events, 7 women (44%) and 9 men (45%) died. Women had a 4.67-fold greater risk of neurologic events (hazard ratio [HR] 4.67, 95% confidence interval [CI] 2.26 to 9.66, p <0.001) compared with men. Women with neurologic events had an increased risk of all-cause mortality compared to women without neurologic event (HR 4.84, 95% CI 1.33 to 17.55, p = 0.017). Similarly, men with neurologic events had an increased risk of all-cause mortality compared to men without neurologic event (HR 4.20, 95% CI 1.93 to 9.17, p <0.001, interaction p = 0.854). In conclusion, among patients with LVAD, women are at greater risk of neurologic event compared to men. Both women and men after LVAD have similar high risk of all-cause mortality after neurologic events., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Transthoracic (TTE) and transesophageal echocardiograms (TEE) are considered accurate in detecting the presence of left ventricular (LV) thrombus. A persistent LV thrombus poses risks of pump thrombosis and stroke in LVAD recipients. The relationship between preoperative echocardiography and intraoperative findings at LVAD implantation has not previously been studied., Methods: A retrospective review examined all patients undergoing LVAD placement or exchange from October 2011 to March 2014. Preoperative TTE and TEE data were validated with presence of LV thrombus during the direct inspection at the time of LVAD placement, and the findings were analyzed quantitatively., Results: Between October 2011 and March 2014, 99 patients underwent a total of 107 LVAD implants. Preoperative TTE was available in 93 (86.9%) cases, while preoperative TEE was available in 37 cases (34.6%). On preoperative TTE, LV thrombus was correctly identified in only two cases, while on preoperative TEE no cases of LV thrombus were identified correctly, and there were 2 false positive reports. Intraoperative inspection revealed presence of LV thrombus in 14 cases. The sensitivity of preoperative TTE was 16.7% and the specificity 100% in detecting LVT, compared to 0% and 93.8%, respectively, for TEE., Conclusions: Preoperative echocardiogram offers low accuracy for presence of LV thrombus. Overall, the sensitivity is too low to reliably exclude thrombus. This could have significant implications in planning off-pump LVAD exchange as thrombus could be missed. More data are necessary to determine whether this could have significant effects on thromboembolic complications and survival.

Aims: Patients with recent onset non-ischaemic cardiomyopathy have a variable clinical course with respect to recovery of left ventricular ejection fraction (LVEF). The aim of this study was to understand whether temporal changes in diastolic function (DF) are associated with clinical outcomes independent of LVEF recovery., Methods and Results: The Intervention in Myocarditis and Acute Cardiomyopathy (IMAC)-2 study was a prospective, multicentre trial investigating myocardial recovery in subjects with symptoms onset of <6 months and LVEF ≤40% of non-ischaemic dilated cardiomyopathy related to idiopathic cardiomyopathy or myocarditis. LVEF and DF were measured at presentation and at 6-month follow-up. Of 147 patients (mean age 46 ± 14 years, 40% female), baseline LVEF was 23 ± 8%. At 6 months, LVEF improved to 41 ± 12%, with 71% increasing by at least 10% ejection fraction units. DF improved in 58%, was unchanged in 28%, and worsened in 14%. Over a mean follow-up of 1.8 ± 1.2 years, there were 18 events: 11 heart failure (HF) hospitalizations, 3 deaths, and 4 heart transplants. LVEF (HR = 0.94, 95% CI 0.91-0.98, P = 0.002) and DF improvements at 6 months (HR = 0.32, 95% CI 0.11-0.92, P = 0.03) were independently associated with lower likelihood for the combined end point of death, transplantation, and HF hospitalization. Diastolic functional improvement at 6-month follow-up was as prognostically important as LVEF recovery for these patients, and provided incremental prognostic value to the risk stratification (X(2) increased from 12.6 to 18, P = 0.02)., Conclusion: In patients with recent onset non-ischaemic cardiomyopathy, DF recovery was associated with favourable outcomes independent of LVEF improvement, adding incremental prognostic value to these patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Black women are at greater risk for peripartum cardiomyopathy (PPCM). The guanine nucleotide-binding proteins β-3 subunit (GNB3) has a polymorphism C825T. The GNB3 TT genotype more prevalent in blacks is associated with poorer outcomes. We evaluated GNB3 genotype and myocardial recovery in PPCM., Methods and Results: A total of 97 women with PPCM were enrolled and genotyped for the GNB3 T/C polymorphism. Left ventricular ejection fraction (LVEF) was assessed by echocardiography at entry, 6 and 12 months postpartum. LVEF over time in subjects with the GNB3 TT genotype was compared with those with the C allele overall and in black and white subsets. The cohort was 30% black, age 30+6, LVEF 0.34+0.10 at entry 31+25 days postpartum. The % GNB3 genotype for TT/CT/CC=23/41/36 and differed markedly by race (blacks=52/38/10 versus whites=10/44/46, P<0.001). In subjects with the TT genotype, LVEF at entry was lower (TT=0.31+0.09; CT+CC=0.35+0.09, P=0.054) and this difference increased at 6 (TT=0.45+0.15; CT+CC=0.53+0.08, P=0.002) and 12 months (TT=0.45+0.15; CT+CC=0.56+0.07, P<0.001.). The difference in LVEF at 12 months by genotype was most pronounced in blacks (12 months LVEF for GNB3 TT=0.39+0.16; versus CT+CC=0.53+0.09, P=0.02) but evident in whites (TT=0.50++0.11; CT+CC=0.56+0.06, P=0.04)., Conclusions: The GNB3 TT genotype was associated with lower LVEF at 6 and 12 months in women with PPCM, and this was particularly evident in blacks. Racial differences in the prevalence and impact of GNB3 TT may contribute to poorer outcomes in black women with PPCM., (© 2016 American Heart Association, Inc.)

Background: Peripartum cardiomyopathy (PPCM) remains a major cause of maternal morbidity and mortality., Objectives: This study sought to prospectively evaluate recovery of the left ventricular ejection fraction (LVEF) and clinical outcomes in the multicenter IPAC (Investigations of Pregnancy Associated Cardiomyopathy) study., Methods: We enrolled and followed 100 women with PPCM through 1 year post-partum. The LVEF was assessed by echocardiography at baseline and at 2, 6, and 12 months post-partum. Survival free from major cardiovascular events (death, transplantation, or left ventricular [LV] assist device) was determined. Predictors of outcome, particularly race, parameters of LV dysfunction (LVEF), and remodeling (left ventricular end-diastolic diameter [LVEDD]) at presentation, were assessed by univariate and multivariate analyses., Results: The cohort was 30% black, 65% white, 5% other; the mean patient age was 30 ± 6 years; and 88% were receiving beta-blockers and 81% angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The LVEF at study entry was 0.35 ± 0.10, 0.51 ± 0.11 at 6 months, and 0.53 ± 0.10 at 12 months. By 1 year, 13% had experienced major events or had persistent severe cardiomyopathy with an LVEF <0.35, and 72% achieved an LVEF ≥0.50. An initial LVEF <0.30 (p = 0.001), an LVEDD ≥6.0 cm (p < 0.001), black race (p = 0.001), and presentation after 6 weeks post-partum (p = 0.02) were associated with a lower LVEF at 12 months. No subjects with both a baseline LVEF <0.30 and an LVEDD ≥6.0 cm recovered by 1 year post-partum, whereas 91% with both a baseline LVEF ≥0.30 and an LVEDD <6.0 cm recovered (p < 0.00001)., Conclusions: In a prospective cohort with PPCM, most women recovered; however, 13% had major events or persistent severe cardiomyopathy. Black women had more LV dysfunction at presentation and at 6 and 12 months post-partum. Severe LV dysfunction and greater remodeling at study entry were associated with less recovery. (Investigations of Pregnancy Associated Cardiomyopathy [IPAC]; NCT01085955)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: This study sought to assess the association between medication utilization, outcome, and the efficacy of resynchronization therapy in the MADIT-CRT study., Methods and Results: Medication use by patients in the MADIT-CRT study was analyzed. Time-dependent Cox proportional hazard regression analyses were performed to assess differences in hospitalization for heart failure (HF) or death. The greater the efficacy of cardiac resynchronization therapy (CRT) as measured by reduction in left ventricular end-systolic volume (LVESV) and increase in left ventricular ejection fraction (LVEF) between baseline and 1 year of follow-up, the greater the likelihood that patients remained on an angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) and avoided use of or reduced treatment with diuretics. Treatment with diuretics was associated with a significantly increased risk of HF hospitalization or death (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.45-2.41; P < .001). In contrast, treatment with an ACE-I/ARB was associated with a significantly decreased risk of HF hospitalization or death (HR 0.58, 95% CI 0.42-0.80; P = .001)., Conclusions: In HF patients in New York Heart Association functional classes I and II and with wide QRS complexes, efficacy of CRT as measured by improvement in LVESV and LVEF was associated with an increased likelihood of remaining on an ACE-I/ARB and discontinuing diuretic therapy. Discontinuation of diuretics was reflective of improved hemodynamic response to CRT., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Left ventricular assist devices (LVADs) have been shown to improve outcomes in advanced heart failure (HF). We hypothesized that LVADs improve glycemic control in HF patients with diabetes mellitus (DM). During a 6 year time period, 202 patients underwent mechanical circulatory support. Of these, 50 patients with DM were included. Data were collected within 2 months before LVAD implantation and at 5.6 ± 1.1 months post-LVAD implant. There was no significant difference in body mass index, hemoglobin, hematocrit, and renal function pre-LVAD and post-LVAD. Fasting blood glucose improved from 136 ± 35 to 108 ± 29 mg/dl post-LVAD (p < 0.001). In 18 patients taking insulin only, daily insulin dose decreased from 43 ± 37 to 29 ± 24 units (p = 0.02). Of the 17 patients taking oral hypoglycemic agents, four did not require antidiabetic medications, six continued the same dose, two required higher doses, and five patients were switched to insulin post-LVAD. In a subset of 22 patients with available data, hemoglobin A1c improved significantly post-LVAD (p < 0.001). C-reactive protein in a subset of 18 patients decreased post-LVAD (p = 0.059). In conclusion, diabetic patients with advanced HF appear to have significant improvement in glycemic control and require less antidiabetic medications post-LVAD.

Although ventricular assist devices (VADs) are lifesaving therapy for patients with severe heart failure, complications such as pump thrombosis can occur. In this report, we present a case of VAD thrombosis following recovery of left ventricular (LV) function. The patient had been supported with a VAD for 8 months, and at the time of presentation, echocardiography revealed near normal native systolic function, aortic valve opening with significant native heart ejection, reduced systolic flow in the outflow and inflow cannulae, and no forward flow through the VAD during diastole. The patient underwent successful VAD explant and examination of the pump revealed thrombus on the rotor. We propose that abnormal flow through the VAD seen with recovery of LV function may contribute to VAD thrombosis.

Life-threatening arrhythmia is an unusual complication of endomyocardial biopsy in transplanted heart. Herein we described a case of VF during endomyocardial biopsy. The possibility of VF during a biopsy necessitates immediate access to defibrillation during endomyocardial biopsy., (©2012, Wiley Periodicals, Inc.)

Background: Given the potential for recovery in recent onset nonischemic cardiomyopathy (ROCM), the timing and need for implantable cardioverter-defibrillator (ICDs) remains controversial. We examined the utilization of ICDs and the impact on survival for subjects with ROCM., Methods and Results: An National Heart, Lung, and Blood Institute sponsored registry enrolled 373 subjects with ROCM, all with a left ventricular ejection fraction (LVEF) ≤0.40 and ≤6 months of symptoms. The mean age was 45 ± 14 years, 38% were female, 21% black, 75% New York Heart Association II/III, and the mean LVEF was 0.24 ± 0.08. Survival was comparable for subjects with an ICD within 1 month of entry (n = 43, 1/2/3 year % survival = 97/97/92) and those with no ICD at 1 month (n = 330, % survival = 98/97/95, P = .30) and between those with and without an ICD at 6 months (ICD, n = 73, 1/2/3 year % survival = 98/98/95; no ICD, n = 300, % survival = 98/96/95, P = .95). There were only 6 sudden cardiac deaths (SCD) noted (% survival free from SCD = 99/98/97) and these occurred in 1.9% of subjects without ICD and 0.9% of those with a device (P = .50)., Conclusions: In a multicenter cohort of ROCM the risk of SCD was low at 1% per year. Early ICD placement did not impact survival and can be deferred while assessing potential for myocardial recovery., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Bcr is a serine/threonine kinase that is a critical regulator of vascular smooth muscle cell inflammation and proliferation. We have previously demonstrated that Bcr acts in part via phosphorylation and inhibition of PPARγ. We have identified the RNA helicase UAP56 as another substrate of Bcr. In this report we demonstrate that knockdown of UAP56 blocks Bcr induced DNA synthesis in vascular smooth muscle cells (VSMC). We also found that over expression of Bcr increased the expression of cyclin E and decreased the expression of p27. Knockdown of UAP56 reversed the effect of Bcr on cyclin E and p27 expression. Furthermore, we found that Bcr binds to UAP56 and demonstrate that binding of UAP56 to Bcr is critical for Bcr induced DNA synthesis in VSMC. Our data identify UAP56 as an important binding partner of Bcr and a novel target for inhibiting vascular smooth muscle cell proliferation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Whether myocardial recovery occurs more frequently in peripartum cardiomyopathy (PPCM) than in recent onset cardiomyopathies in men and nonperipartum women has not been prospectively evaluated. This was examined through an analysis of outcomes in the Intervention in Myocarditis and Acute Cardiomyopathy 2 (IMAC2) registry., Methods and Results: IMAC2 enrolled 373 subjects with recent onset nonischemic dilated cardiomyopathy. Left ventricular ejection fraction (LVEF) was assessed at entry and 6 months, and subjects followed for up to 4 years. Myocardial recovery was compared between men (group 1), nonperipartum women (group 2) and subjects with PPCM (group 3). The cohort included 230 subjects in group 1, 104 in group 2, and 39 in group 3. The mean LVEF at baseline in groups 1, 2, and 3 was 0.23 ± 0.08, 0.24 ± 0.08, and 0.27 ± 0.07 (P = .04), and at 6 months was 0.39 ± 0.12, 0.42 ± 0.11, and 0.45 ± 0.14 (P = .007). Subjects in group 3 had a much greater likelihood of achieving an LVEF >0.50 at 6 months than groups 1 or 2 (19 %, 34%, and 48% respectively, P = .002)., Conclusions: Prospective evaluation confirms myocardial recovery is greatest in women with PPCM, poorest in men, and intermediate in nonperipartum women. On contemporary therapy, nearly half of women with PPCM normalize cardiac function by 6 months., (Copyright © 2012 Elsevier Inc. All rights reserved.)