Less Invasive Left Ventricular Assist Device Implantation Is Safe and Feasible in Patients With Smaller Body Surface Area.

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 m2) and normal/large BSA (>1.8 m2). 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.

Left atrial appendage exclusion with less invasive left ventricular assist device implantation.

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.

Impact of surgical approach for left ventricular assist device implantation on postoperative invasive hemodynamics and right ventricular failure.

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.

Study results suggest less invasive HeartMate 3 implantation is a safe and effective approach for obese patients.

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/m2) 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.

Smoking and the Risk of Stroke in Patients with a Left Ventricular Assist device.

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.

Enhanced Recovery After Surgery in Patients Implanted with Left Ventricular Assist Device.

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.

HeartMate 3 pump exchange via sternal-sparing bilateral minithoracotomies.

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.

Implantation of a fully magnetically levitated left ventricular assist device using a sternal-sparing surgical technique.

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.

Clinical Significance of Early Hospital Readmission in Continuous-Flow Left Ventricular Assist Device Patients.

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.

Complete Sternal-Sparing HeartMate 3 Implantation: A Case Series of 10 Consecutive Patients.

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.

Small proline-rich protein 2B drives stress-dependent p53 degradation and fibroblast proliferation in heart failure.

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-ß1 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.

Influence of Diabetes Mellitus on Outcomes in Patients After Left Ventricular Assist Device Implantation.

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.

Myocardial Damage Detected by Late Gadolinium Enhancement Cardiac Magnetic Resonance Is Uncommon in Peripartum Cardiomyopathy.

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/m2 [Q1-Q3 83-134 mL/m2]), 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.

Ventricular fibrillation complicating endomyocardial biopsy of transplanted heart.

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.

Cyclophilin A is an inflammatory mediator that promotes atherosclerosis in apolipoprotein E-deficient mice.

Cyclophilin A (CyPA; encoded by Ppia) is a ubiquitously expressed protein secreted in response to inflammatory stimuli. CyPA stimulates vascular smooth muscle cell migration and proliferation, endothelial cell adhesion molecule expression, and inflammatory cell chemotaxis. Given these activities, we hypothesized that CyPA would promote atherosclerosis. Apolipoprotein E-deficient (Apoe(-/-)) mice fed a high-cholesterol diet for 16 wk developed more severe atherosclerosis compared with Apoe(-/-)Ppia(-/-) mice. Moreover, CyPA deficiency was associated with decreased low-density lipoprotein uptake, VCAM-1 (vascular cell adhesion molecule 1) expression, apoptosis, and increased eNOS (endothelial nitric oxide synthase) expression. To understand the vascular role of CyPA in atherosclerosis development, bone marrow (BM) cell transplantation was performed. Atherosclerosis was greater in Apoe(-/-) mice compared with Apoe(-/-)Ppia(-/-) mice after reconstitution with CyPA(+/+) BM cells, indicating that vascular-derived CyPA plays a crucial role in the progression of atherosclerosis. These data define a role for CyPA in atherosclerosis and suggest CyPA as a target for cardiovascular therapies.

Bcr kinase activation by angiotensin II inhibits peroxisome-proliferator-activated receptor gamma transcriptional activity in vascular smooth muscle cells.

Bcr is a serine/threonine kinase activated by platelet-derived growth factor that is highly expressed in the neointima after vascular injury. Here, we demonstrate that Bcr is an important mediator of angiotensin (Ang) II and platelet-derived growth factor-mediated inflammatory responses in vascular smooth muscle cells (VSMCs). Among transcription factors that might regulate Ang II-mediated inflammatory responses we found that ligand-mediated peroxisome proliferator-activated receptor (PPAR)gamma transcriptional activity was significantly decreased by Ang II. Ang II increased Bcr expression and kinase activity. Overexpression of Bcr significantly inhibited PPARgamma activity. In contrast, knockdown of Bcr using Bcr small interfering RNA and a dominant-negative form of Bcr (DN-Bcr) reversed Ang II-mediated inhibition of PPARgamma activity significantly, suggesting the critical role of Bcr in Ang II-mediated inhibition of PPARgamma activity. Point-mutation and in vitro kinase analyses showed that PPARgamma was phosphorylated by Bcr at serine 82. Overexpression of wild-type Bcr kinase did not inhibit ligand-mediated PPARgamma1 S82A mutant transcriptional activity, indicating that Bcr regulates PPARgamma activity via S82 phosphorylation. DN-Bcr and Bcr small interfering RNA inhibited Ang II-mediated nuclear factor kappaB activation in VSMCs. DN-PPARgamma reversed DN-Bcr-mediated inhibition of nuclear factor kappaB activation, suggesting that PPARgamma is downstream from Bcr. Intimal proliferation in low-flow carotid arteries was decreased in Bcr knockout mice compared with wild-type mice, suggesting the critical role of Bcr kinase in VSMC proliferation in vivo, at least in part, via regulating PPARgamma/nuclear factor kappaB transcriptional activity.