Left Ventricular Assist Device Placement Research Articles

426 A Beat Away from Precision Medicine: Characterizing Human Cardiac Fibroblast Responsiveness to Hemodynamic Unloading in Heart Failure with Reduced Ejection Fraction

OBJECTIVES/GOALS: Myocardial interstitial fibrosis leads to high hemodynamic load resulting in heart failure (HFrEF). Previous studies show that treatment with a left ventricular assist device (LVAD) does not reduce fibrosis. We hypothesize that human cardiac fibroblasts are highly activated in HFrEF and remain unresponsive to hemodynamic unloading by LVAD. METHODS/STUDY POPULATION: Forty human subjects with HFrEF undergoing LVAD implantation were enrolled to provide a portion of myocardium routinely removed during LVAD placement. In addition, 7 biopsies previously collected from transplanted hearts with extended LVAD treatment were also evaluated (LVEX). RESULTS/ANTICIPATED RESULTS: Quantification of PSR-stained sections reveals a significant increase in collagen content in the HFrEF tissue (CVF = 2.8) compared to control tissues (CVF = 0.9) that remained elevated in LVEX hearts (CVF = 3.1). HCFs from LV biopsies were isolated and grown to confluence. HCFs from HFrEF patients and control HCFs were plated on substrates with stiffnesses reflective of normal myocardium (2kPa) or HFrEF myocardium (8kPa). Cells were collected at 4- and 7-day time points and levels of collagen I and alpha-smooth muscle actin were quantified by western blot analysis. Control HCFs were responsive to changes in substrate stiffness producing more Col I and a-SMA on 8kPa versus 2kPa, HCFs from HFrEF patients were unresponsive to changes in stiffness exhibiting no significant difference in protein production on 2 vs. 8kPa. DISCUSSION/SIGNIFICANCE: Our data suggests that HCFs isolated from the failing myocardium do not respond to changes in mechanical load and might contribute to persistent increases in fibrosis. These findings bring us one step closer to elucidating mechanisms behind fibrosis in HFrEF which could lead to targeted therapies to improve patient outcomes from LVAD support.

Right Ventricular Assist Device Placement During Left Ventricular Assist Device Implantation Is Associated With Improved Survival.

Right ventricular failure (RVF) is a significant cause of mortality in patients undergoing left ventricular assist device (LVAD) implantation. Although right ventricular assist devices (RVADs) can treat RVF in the perioperative LVAD period, liberal employment before RVF is not well established. We therefore compared the survival outcomes between proactive RVAD placement at the time of LVAD implantation with a bailout strategy in patients with RVF. Retrospectively, 75 adult patients who underwent durable LVAD implantation at our institution and had an RVAD placed proactively before LVAD implantation or as a bailout strategy postoperatively due to hemodynamically unstable RVF were evaluated. Patients treated with a proactive RVAD strategy had lower Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) and a higher proportion of these required temporary mechanical circulatory support (MCS) preoperatively. Preoperative hemodynamic profiling showed a low pulmonary artery pulsatility index (PAPi) score of 1.8 ± 1.4 and 1.6 ± 0.94 (p = 0.42) in the bailout RVAD and proactive RVAD groups, respectively. Survival at 3, 6, and 12 months post-LVAD implantation was statistically significantly higher in patients who received a proactive RVAD. Thus, proactive RVAD implantation is associated with short- and medium-term survival benefits compared to a bailout strategy in RVF patients undergoing LVAD placement.

Pre- and Post-Implant Endoscopy in Left Ventricular Assist Device Recipients: A Single-Center Experience.

Gastrointestinal bleeding (GIB) is common in left ventricular assist devices (LVADs) patients, but the optimal screening approach before LVAD implantation is still unclear. The aim of the study was to describe our experience with pre- and post-LVAD implantation endoscopic screening and subsequent GI bleeding in this cohort. A retrospective review was conducted among all patients who underwent LVAD implantation at Saint Luke's Hospital, between 2010 and 2020. The data were reviewed to determine the yield and safety of endoscopic procedures performed within 1 month before LVAD placement and the incidence of GIB within 1 year after implantation. A total of 167 LVAD patients met the inclusion criteria, and 23 underwent pre-implantation endoscopic evaluation. Angiodysplasia had a significantly higher odds ratio (OR) of 9.41 (95% confidence interval (CI): 2.01 - 44.09) in post-LVAD endoscopy, while there was no significant difference in bleeding from other sources such as peptic ulcer disease or diverticular bleeding. There was no difference in the incidence of GIB in patients who underwent endoscopic evaluation pre-LVAD compared to post-LVAD GIB (32.6% vs. 39.1%, P = 0.64). Endoscopy was well-tolerated in this cohort, and argon plasma coagulation was the most commonly used intervention to achieve hemostasis. According to our results, we recommend against routine pre-LVAD endoscopic screening. Instead, we suggest an individualized approach, where decisions are made on a case-by-case basis.

Postoperative care of 14 patients with left ventricular assist devices: a case series.

A left ventricular assist device is a mechanical device that is surgically implanted in the heart to partially or completely replace the function of the heart. Left ventricular assist devices are of vital importance in the treatment of patients with heart failure. There are different recommendations for the postoperative care of patients undergoing left ventricular assist device implantation in different countries, and no uniform standard has been developed. The first implantation of a left ventricular assist device in Eastern China was performed in February 2021; since that date, 14 patients underwent implantation until February 2023. This report describes the postoperative care of these 14 patients with end-stage heart failure who underwent left ventricular assist device placement, all of whom were discharged with a good prognosis.

Inhaled Pulmonary Vasodilators for the Treatment of Right Ventricular Failure in Cardio-Thoracic Surgery: Is One Better than the Others?

Right ventricular failure (RFV) is a potential complication following cardio-thoracic surgery, with an incidence ranging from 0.1% to 30%. The increase in pulmonary vascular resistance (PVR) is one of the main triggers of perioperative RVF. Inhaled pulmonary vasodilators (IPVs) can reduce PVR and improve right ventricular function with minimal systemic effects. This narrative review aims to assess the efficacy of inhaled nitric oxide and inhaled prostacyclins for the treatment of perioperative RVF. The literature, although statistically limited, supports the clinical similarity between them. However, it failed to demonstrate a clear benefit from the pre-emptive use of inhaled nitric oxide in patients undergoing left ventricular assist device implantation or early administration during heart-lung transplants. Additional concerns are related to cost safety and IPV use in pathologies associated with pulmonary venous congestion. The largest ongoing randomized controlled trial on adults (INSPIRE-FLO) is addressing whether inhaled Epoprostenol and inhaled nitric oxide are similar in preventing RVF after heart transplants and left ventricular assist device placement, and whether they are similar in preventing primary graft dysfunction after lung transplants. The preliminary analysis supports their equivalence. Several key points may be achieved by the present narrative review. When RVF occurs in the setting of elevated PVR, IPV should be the preferred initial treatment and they should be preventively used in patients at high risk of postoperative RVF. If severe refractory postoperative RVF occurs, IPVs should be combined with complementary pharmacology (inotropes and inodilators). If unsuccessful, right ventricular mechanical support should be established.

Does concomitant tricuspid valve intervention at the time of left ventricular assist device placement for patients with significant tricuspid regurgitation lead to improved outcomes compared to isolated left ventricular assist device placement?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'In patients with advanced heart failure (HF) and moderate to severe functional tricuspid regurgitation (TR) undergoing left ventricular assist device (LVAD) placement is concomitant tricuspid valve intervention (TVI) superior for the clinical outcomes of survival, right ventricular failure, rehospitalizations for HF, functional status, and quality of life?' Altogether, 56 papers were found using the reported search, of which 12 papers represented the best evidence to answer the clinical question. The authors, journal, date, country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Our search found no significant clinical benefit for concomitant TVI at the time of LVAD placement. We conclude that patient with moderate-to-severe TR should not routinely undergo concomitant TVI with LVAD placement.

2763. Evaluating the Safety and Effectiveness of Long-term Antibiotic Suppression in Patients with Left Ventricular Assist Devices

Abstract Background The utilization of left ventricular assist devices (LVADs) as a bridge to transplantation or destination therapy for non-transplant candidates continues to rise. Unfortunately, infection remains one of the most common complication and lack of definitive source control often leads to the decision to initiate long-term antibiotic suppression. The purpose of this retrospective cohort study is to evaluate the long-term safety and effectiveness of antibiotic suppression following an LVAD-related or LVAD-specific infection. Methods Adults who underwent LVAD placement between August 2018 and September 2022 at Prisma Health Midlands and received antibiotic suppression for an LVAD-related or LVAD-specific infection were evaluated. Safety was evaluated as a composite endpoint of treatment emergent adverse events, and discontinuation of or decrease in dose due to tolerability concerns. Effectiveness was evaluated as the proportion of patients without a suppression emergent infection (SEI) within six months of antibiotic suppression initiation. Patients experiencing a SEI (failure) were compared to those without an SEI (success) at six months. Secondary outcomes included the proportion of patients experiencing early SEI within 90 days of antibiotic suppression initiation and evaluation of factors associated with success of antibiotic suppression at six months. Results Fifty-one patients received antibiotic suppressive therapy following an LVAD-related or LVAD-specific index infection. Patients were followed for a minimum of 6 months and an average 2.8 years. Treatment emergent adverse events occurred in 4 (7.8%) patients, with 2 events leading to antibiotic discontinuation. SEI occurred in 9 (17.6%) of patients at 6 months with the most common organisms being P. aeruginosa, S. aureus, and S. epidermidis. Early SEI was observed in 4 (7.8%) patients. Overall, SEI occurred in 28 patients (55%) at a median 341 days (IQR 157-502). Documented resistance to suppressive antibiotic was observed in 13 (25.4%) patients. Index infections with a gram-negative organism was significantly more common in those experiencing SEI (80% vs. 47%, p=0.031). Conclusion Antibiotic suppression following LVAD-associated infections is well-tolerated and successful in 82% of patients at 6 months. Disclosures Julie Ann Justo, PharmD, MS, FIDSA, BCPS, Gilead Sciences: Advisor/Consultant|Shionogi: Advisor/Consultant|Vaxart: Stocks/Bonds

Ventricular assist devices and sleep-disordered breathing-A mechanical heart stimulating a sleepy brain.

Sleep-disordered breathing, including obstructive sleep apnea (OSA) and central sleep apnea (CSA), is common in severe heart failure (HF) patients. There is limited data on the effect of left ventricular assist devices (LVAD) on sleep apnea. We performed a retrospective review of 350 durable LVAD patients and found 5 with a history of pre- and post-LVAD sleep studies. All five patients had OSA, and three had concomitant CSA. We observed reduced apnea-hypopnea index following LVAD placement. This was due to a near abolishment of CSA in three mixed sleep apnea patients-as seen by a central apnea index improvement from an average of 25.9 ± 13.1 to 1.4 ± 2.5 events per hour (p = 0.063). LVAD placement was associated with an increase in thermodilution cardiac output from 2.7 ± 0.6 to 4.1 ± 1.1 L/min (p = 0.014). These findings support chemoreception physiology seen in patients with poor circulation and the effect of restoring this circulation with LVAD support.

Abstract 16193: Differences in Mortality Between Patients With Left Ventricular Assist Devices and End-Stage Renal Disease on Peritoneal Dialysis versus Hemodialysis

Introduction: End-stage renal disease (ESRD) patients with concomitant heart failure often require left ventricular assist devices (LVADs), but the impact on mortality in peritoneal dialysis (PD) versus hemodialysis (HD) is unclear. This study aims to compare mortality rates in prevalent and incident ESRD patients with LVADs on PD versus HD. Hypothesis: We hypothesize differences in mortality rates and heart transplantation rates between LVAD patients on PD versus HD. Methods: A retrospective cohort analysis used data from the TriNetX Research Network database. Propensity score matching compared two cohorts: LVAD with HD (Cohort 1) and LVAD with PD (Cohort 2). Demographic data, comorbidities, and baseline laboratory values were collected. Mortality rates were assessed using risk analyses over a 3-year period following LVAD placement. Results: The study cohorts included 252 patients each after propensity score matching, with mean ages of 63.8 ± 14.3 years (Cohort 1) and 62.87 ± 15.4 years (Cohort 2). No significant differences were observed in demographic data including gender, race, or ethnicity between the two cohorts. The mortality rate did not significantly differ between Cohort 1 (HD) and Cohort 2 (PD) (0.563 vs. 0.603), with a risk difference of -0.04 (95% CI: -0.126, 0.046, p = 0.366). The risk ratio and odds ratio for mortality also showed no significant differences. Conclusion: ESRD patients with LVADs receiving PD demonstrated similar mortality rates compared to those receiving HD. These findings suggest that dialysis modality does not seem to influence mortality outcomes in patients with LVAD. Further research is needed to better understand the differences between these complex patient populations.

Abstract 15640: Long Term Event-Free Survival in Patients With Ischemic and Non-Ischemic Cardiomyopathy up to Thirteen Years Following Cell-Based Therapy: Results From the Hyperion Observational Cohort

Introduction: The long-term clinical outcomes of cell-based therapies to treat ischemic (ICM) and non-ischemic dilated cardiomyopathy (NIDCM) are unknown. We therefore prospectively followed patients (pts) with ICM/NICDM treated by targeted transcatheter endocardial mesenchymal stromal cell (MSC) injections (TESI). Methods: Of the 155 pts enrolled in prior MSC TESI studies, 111 were eligible to be contacted. Of these, 47 (42%) agreed to participate and have periodic follow-up assessments (Cardiac MRI/CT, 6MWT, labs, PE, EKG, and MLHFq) for up to 13 years following their index procedure. Time-to-event information was captured from all 155 former participants. Endpoints included event-free survival, changes in left ventricular ejection fraction (EF), and ventricular remodeling. Clinical endpoint events were defined as the composite of: Death (all-cause mortality), Left Ventricular Assist Device (LVAD) placement, or Heart Transplant. Descriptive statistics were used to classify the sample, and Kaplan-Meier survival analysis was generated to examine time-to-event trends. Results: There were 134 men and 21 women, mean age 60.0±11.0 years, including 121 (78%) with ICM, and 34 (22%) with NIDCM. In pts with ICM, mean EF at baseline was 31 %±10.8% and after 1 year was 32.6%±11.8% (P=0.08). In pts with NIDCM baseline EF was 27%±10% and increased to 34%±13% after 1 year (P=0.002). Overall, 40% of pts had a decrease in LVEF, 26% had <5% increase, 34% had a ≥5% increase, and 17% had a ≥10% increase in LVEF after 1 year. Increases of ≥5% LVEF post-therapy were associated with longer event-free survival in NIDCM (OR: 2.57; 95% CI: 0.6, 11.1) but not ICM (OR: 1.25; 95% CI: 0.4, 3.6). Conversely, reductions in LVEDV were associated with longer event-free survival in ICM (OR: 7.23; 95% CI: 1.9, 27.1) but not NIDCM (OR: 1.88; 95% CI: 0.4, 10.0). Conclusion: In this long-term observational cohort analysis, improvement of EF and/or reduction in LVEDV was associated with survival benefits among pts with NIDCM and ICM respectively. Future studies are needed with placebo controls to determine which pts are most likely to respond to MSC therapy. Clinical Trial Registration: URL: http://www.clinicaltrials.gov.; Unique ID: NCT03071835.

Abstract 13507: Outcomes Among Coronary Artery Disease Patients Hospitalized for Left Ventricular Assist Device Implantation: A United States Population-Based Cohort Study

Introduction: Coronary Artery Disease (CAD) is a significant cause of morbidity and mortality among the general population. Previous studies suggested that significant CAD increased the risk for adverse outcomes including acute coronary syndrome and ischemic cardiomyopathy, which if severe enough warrants advance therapeutic options including implantation of a left ventricular assist device (LVAD). However, there is paucity of data exploring the in-hospital outcomes of patients with CAD admitted for LVAD implantation. Hypothesis: CAD does not impact outcomes in patients undergoing LVAD implantation. Methods: A retrospective cohort study using the National Inpatient Sample 2018-2020 database. Patients aged > 18 years with known CAD admitted for LVAD placement were identified in the database. Multivariate logistic regression analysis was used to adjust for potential patients' and hospital level confounders. Outcome of interest were in-hospital mortality, ST-Elevation Myocardial Infarction (STEMI), LVAD thrombosis and ischemic stroke among patients with CAD hospitalized for LVAD implantation. Results: We identified a total of 76,757 patients admitted for LVAD implantation in the years 2018-2020, of which 55.93% (n= 42,930/76,757) had CAD. The overall mortality rate among patients admitted for LVAD implantation was 27.47% (n=21,080/76,757). Among those with concomitant CAD, the mortality rate was significantly higher at 28.93% (12,263/42,930, P=0.00). Using a stepwise survey multivariable logistic regression model that adjusted for patient and hospital level confounders, concomitant CAD among LVAD recipients was found to be an independent predictor of overall in-hospital mortality (aOR 1.24; 95% CI (Confidence Interval), 1.14-1.36; p<0.001) but did not increase the risk of STEMI (aOR 1.48; 95% CI, 0.98-1.34; p=0.09), LVAD thrombosis (aOR 1.04; 95% CI, 0.51-2.14; p=0.91) and ischemic stroke (aOR 0.76; 95% CI, 0.38-1.39; p=0.33). Conclusions: Among hospitalized patients for LVAD implantation, concurrent CAD increased the risk for in-hospital mortality but did not increase the risk for STEMI, LVAD thrombosis and ischemic stroke. Prospective studies with control of potential confounders may better delineate these associations.

Abstract 16737: Explantation of LVAD in Recovered Alcohol Induced Cardiomyopathy

Durable Left Ventricular Assist Device (LVAD) is an important modality for bridge or destination therapy for patients with end-stage heart failure. However, there is a paucity of evidence guiding management for LVAD explantation in patients with sufficient myocardial recovery as this only occurs in 1-3% of cases. We present a case of a patient with LVAD placement due to alcoholic cardiomyopathy with subsequent removal of his LVAD three years later. Description of Case: A 51-year-old male with a history of alcohol induced cardiomyopathy with an LV ejection fraction of 10% s/p Heartmate II LVAD implant 3 years ago was evaluated for LVAD explantation. Over the course of one year, LVAD speed was decreased and ejection fraction (EF), cardiac output (CO) and cardiac index (CI) were monitored. Prior to explantation, the patients EF was 50% with a CO of 5.6L/min and CI 2.7 L/min/m2. Following successful explantation, a repeat echocardiogram 3 months later revealed an EF of 45%. Right heart catheterization revealed CO of 5.3L/min and CI 2.6L/min/m2. Patient was discharged on guideline directed medical therapy with continued improvement. Discussion: Mechanical, histological, and biochemical myocardial improvement has been described in LVAD recipients. There is a paucity of data to guide recovery assessment and candidacy for explantation. The 2023 ISHLT guidelines have attempted to synthesize the available data and outline the major considerations. Assessment should be done at low LVAD speeds with incorporation of data from patient’s clinical status, echocardiography, right heart catheterization, and cardiopulmonary exercise testing. Utilization of LVAD as a bridge to recovery was feasible in our patient given careful assessment of recovered cardiac function as outlined by aforementioned criteria. LVAD explantation after heart recovery remains a rare phenomenon. As access to cardiac transplantation remains limited, consistent use of guideline directed medical therapy allows for the possibility of heart recovery along with explantation. We present a case of successful and maintained myocardial recovery after LVAD explantation. Cases such as this would benefit from standardization of LVAD explantation guidelines for optimal long-term survival for patients.

Abstract 18363: Readmission & Temporal Trends of Post LVAD Placement Complications in Patients With End-Stage Heart Failure

Introduction: 5-10% of heart failure (HF) patients progress to advanced stages. Left ventricular assist devices (LVADs) have emerged as a favored therapy for end-stage HF as destination therapy or as a bridge to heart transplantation. However, complications and provider expertise hinder its widespread use. Third generation LVAD was introduced in 2018 to enhance usability and reduce complications. We aim to investigate the temporal trends in post-LVAD complications with the latest generation LVAD vs the previous version. Methods: We utilized the 2016-2020 Nationwide Readmission Database to identify patients ≥ 18 years of age with advanced HF implanted with an LVAD. Variables were identified using International Classification of Diseases, Tenth revision codes. We compared 2 groups based on the implant year (2016-2018 and 2019-2020). The primary outcome was 30-day readmission (30-dr), while secondary outcomes were trends in complications, mortality rate, and healthcare cost. Multivariate analyses and descriptive bivariate analyses were performed. A p-value <0.05 was considered statistically significant. Results: We identified 7,975 patients (21.3% females) of which 17.1 % (n = 1,214) were readmitted within 30 days. Readmission rates were 17.7% (n = 778) for 2016-2018 and 16.2% (n = 435) for 2019-2020 (adjusted Wald test, p = 0.26). The 2019-2020 group exhibited lower rates of cardiac device complications, vasopressor usage, cardiac tamponade, and peri-procedural circulatory complications than the 2016-2018 group (adjusted Wald test, p < 0.05). No significant differences in mortality or LOS were observed between the two groups (adjusted Wald test, p > 0.05). Healthcare costs were higher in the 2019-2020 group (mean $276,439 vs $315,332, adjusted Wald test, p = 0.01). Conclusions: Complications following LVAD placement continue to impede broader adoption for advanced HF. Nonetheless, advancements in newer LVAD generations and improved provider expertise hold promise for increased utilization. Our study indicates a decline in complications, including cardiac tamponade and post-procedural complications, which may be attributed to newer device innovations. Further research is necessary to explore this correlation in greater depth.

The Roles of Venopulmonary Arterial Extracorporeal Membrane Oxygenation.

Concise definitive review of the use of venopulmonary arterial extracorporeal membrane oxygenation (V-PA ECMO) support in patients with cardiopulmonary failure. Original investigations identified through a PubMed search with search terms "percutaneous right ventricular assist device," "oxy-RVAD," "V-PA ECMO," and "veno-pulmonary arterial ECMO" were reviewed and evaluated for relevance. Studies that included more than three patients supported with V-PA ECMO were included. Clinically relevant data from included studies, including patient-important outcomes, were summarized and discussed. We identified four groups of patients where V-PA ECMO has been studied: acute respiratory distress syndrome, right ventricular dysfunction after left ventricular assist device placement, bridge to lung transplantation, and pulmonary embolism. Most identified works are small, single center, and retrospective in nature, precluding definitive conclusions regarding the efficacy of V-PA ECMO. There have been no clinical trials evaluating the efficacy of V-PA ECMO for any indication. V-PA ECMO is a promising form of extracorporeal support for patients with right ventricular dysfunction. Future work should focus on identifying the optimal timing and populations for the use of V-PA ECMO.

Sex-based differences in left ventricular assist device clinical outcomes.

Heart failure (HF) continues to be a significant public health issue, posing a heightened risk of morbidity and mortality for both genders. Despite the widespread use of left ventricular assist device (LVAD), the influence of gender differences on clinical outcomes following implantation remains unclear. We investigated the impact of gender differences on readmission rates and other outcomes following LVAD implantation in patients admitted with advanced HF. We conducted a retrospective study of patients who underwent LVAD implantation for advanced HF between 2014 and 2020, using the Nationwide Readmissions Database. Our study cohort was divided into male and female patients. The primary outcome was 30-day readmission (30-dr), while secondary outcomes were inpatient mortality, length of stay (LOS), procedural complication rates, and periadmission rates. Multivariate linear, Cox, and logistic regression analyses were performed. During the study period, 11,492 patients with advanced HF who had LVAD placement were identified. Of these, 22% (n = 2532) were females and 78% (n = 8960) were males. The mean age was 53.9 ± 10.8 years for females and 56.3 ± 10.5 years for males (adjusted Wald test, p < 0.01). Readmissions were higher in females (21% vs. 17%, p = 0.02) when compared to males. Cox regression analysis showed higher readmission events (hazard ratio: 1.24, 95% confidence interval: 1.01-1.52, p = 0.03) in females when compared to males. Inpatient mortality, LOS, and most procedural complication rates were not statistically significantly different between the two groups (p > 0.05, all). Women experienced higher readmission rates and were more likely to be readmitted multiple times after LVAD implantation when compared to their male counterparts. However, there were no significant sex-based differences in inpatient mortality, LOS, and nearly all procedural complication rates. These findings suggest that female patients may require closer monitoring and targeted interventions to reduce readmission rates.

S831 Outcomes, Trends, and Predictors of Gastrointestinal Bleeding in Patients Undergoing Left Ventricular Assist Device Placement: A Nationwide and Propensity Matched Analysis of United States

S831 Outcomes, Trends, and Predictors of Gastrointestinal Bleeding in Patients Undergoing Left Ventricular Assist Device Placement: A Nationwide and Propensity Matched Analysis of United States

Abstract P2111: Characterizing Human Cardiac Fibroblast Responsiveness To Hemodynamic Unloading In Heart Failure With Reduced Ejection Fraction

Background: Myocardial interstitial fibrosis is a common pathology in cardiomyopathies leading to ventricular dilation and increased hemodynamic load that result in heart failure with reduced ejection fraction (HFrEF). Previous research has shown that HFrEF patients treated with a left ventricular assist device (LVAD) undergo hemodynamic unloading resulting in at least partial cardiomyocyte recovery. However, evidence supports that these patients do not experience a regression of fibrosis and demonstrate, in some cases, a worsening of fibrosis after LVAD treatment. Purpose: We hypothesize that human cardiac fibroblasts (HCFs) are constitutively activated in HFrEF myocardium but remain unresponsive to hemodynamic unloading with LVAD placement. Methods and Results: Forty human subjects with HFrEF undergoing LVAD implantation were enrolled to provide a portion of myocardium routinely removed during LVAD placement. In addition, 7 biopsies previously collected from transplanted hearts with extended LVAD treatment were also evaluated (LVEX). Quantification of PSR stained sections revealed a significant increase in collagen content in the HFrEF tissue (Collagen volume fraction % (CVF) = 2.8±0.2) in comparison to control tissues (CVF = 0.9±0.2) that remained elevated in LVEX hearts (CVF = 3.1±0.3). HCFs derived from biopsies received at LVAD placement were isolated and grown to confluence. HCFs from HFrEF patients and control HCFs from healthy donors were then plated on substrates with mechanical stiffnesses reflective of either normal myocardium (2kPa) or failing myocardium (8kPa). Cells were collected at 4- and 7-day timepoints and levels of collagen I (Col I) and alpha-smooth muscle actin (α-SMA) were quantified through western blot analysis with β-actin as a loading control. Whereas control HCFs were responsive to changes in substrate stiffness producing more Col I and α-SMA on 8kPa versus 2kPa, HCFs from HFrEF patients were unresponsive to changes in stiffness exhibiting no significant difference in production on 2 vs. 8kPa. Conclusion: These data suggest that HCFs isolated from the failing myocardium do not respond to changes in mechanical load and hence, might contribute to persistent increases in fibrosis in failing and unloaded hearts.

Association of Hospital Procedural Volume With Outcomes of Left Ventricular Assist Device Placement

With the advancement in device technology, the use of durable left ventricular assist devices (LVADs) has increased significantly in recent years. However, there is a dearth of evidence to conclude whether patients who undergo LVAD implantation at high-volume centers have better clinical outcomes than those receiving care at low- or medium-volume centers. We analyzed the hospitalizations using the Nationwide Readmission Database for the year 2019 for new LVAD implantation. Baseline comorbidities and hospital characteristics were compared among low- (1-5 procedures/year), medium- (6-16 procedures/year) and high-volume (17-72 procedures/year) hospitals. The volume/outcome relationship was analyzed using the annualized hospital volume as a categorical variable (tertiles) as well as a continuous variable. Multilevel mixed-effect logistic regression and negative binomial regression models were used to determine the association of hospital volume and outcomes, with tertile 1 (low-volume hospitals) as the reference category. A total of 1533 new LVAD procedures were included in the analysis. The inpatient mortality rate was lower in the high-volume centers compared with the low-volume centers (9.04% vs 18.49%, aOR 0.41, CI0.21-0.80; P = 0.009). There was a trend toward lower mortality rates in medium-volume centers compared with low-volume centers; however, it did not reach statistical significance (13.27% vs 18.49%, aOR 0.57, CI0.27-1.23; P = 0.153). Similar results were seen for major adverse events (composite of stroke/transient ischemic attack and in-hospital mortality). There was no significant difference in bleeding/transfusion, acute kidney injury, vascular complications, pericardial effusion/hemopericardium/tamponade, length of stay, cost, or 30-day readmission rates between medium- and high-volume centers compared to low-volume centers. Our findings indicate lower inpatient mortality rates in high-volume LVAD implantation centers and a trend toward lower mortality rates in medium-volume LVAD implantation centers compared to lower-volume centers.

In-hospital stroke and mortality trends after left ventricular assist device implantation in the United States from 2017 to 2019.

The newer Left Ventricular Assist Device (LVAD), the HeartMate 3 (HM3), was initially approved by the Food and Drug Administration in 2017. We aimed to describe the temporal trends of in-hospital stroke and mortality among patients who underwent LVAD placement between 2017 and 2019. The National Inpatient Sample was queried from 2017 to 2019 to identify all adults with heart failure and reduced ejection fraction (HFrEF) who underwent LVAD implantation using the International Classification of Diseases 10th Revision codes. The Cochran-Armitage test was conducted to assess the linear trend of in-hospital stroke and mortality. In addition, multivariable regression analysis was conducted to assess the association of LVAD placement with in-hospital stroke and death. A total of 5,087,280 patients met the selection criteria. Of those, 11,750 (0.2%) underwent LVAD implantation. There was a downtrend in in-hospital mortality per year (trend: -1.8%, p = 0.03), but not in the trend of both ischemic and hemorrhagic stroke per year. LVAD placement was associated with greater odds of stroke of any type (OR = 1.96, 95% CI 1.68-2.29, p < 0.001) and in-hospital mortality (OR = 1.37, 95% CI 1.16-1.61, p < 0.001). Our study found a significant downtrend in the in-hospital mortality rates among patients with LVAD without substantial changes in stroke rate trends over the study timeframe. As stroke rates remained steady, we hypothesize that improved management along with better control of blood pressure, could have played an important role in survival benefit over the study time frame.

Clinical Characteristics and Outcomes of Clostridioides difficile Infection in Patients With Left Ventricular Assist Device.

The literature regarding Clostridioides difficile infection (CDI) in left ventricular assist devices (LVADs) patients is limited. Therefore, we aimed to characterize the clinical course, risk factors, management, and outcomes of LVAD patients who developed CDI. Adult patients who underwent LVAD placement during 2010-2022 and developed CDI were included. To determine risk factors and outcomes, we matched CDI patients with LVAD patients who did not develop CDI. Each CDI case was matched with up to two control subjects by age, sex, and time from LVAD implantation. Forty-seven of 393 LVAD patients (12.0%) developed CDI. The median time from LVAD implantation to CDI was 147 days (interquartile range 22.5-647.0). The most common CDI treatment was oral vancomycin (n = 26, 55.3%). Thirteen patients (27.7%) required treatment extension because of a lack of clinical response. Three patients (6.4%) developed recurrent CDI. When 42 cases were matched to 79 control subjects, antibiotic exposure within 90 days was significantly associated with CDI (adjusted odds ratio 5.77; 95% confidence interval, 1.87-17.74; p = 0.002). Moreover, CDI was associated with 1 year mortality (adjusted hazard ratio 2.62; 95% confidence interval, 1.18-5.82; p = 0.018). This infection occurs most often within the first year after LVAD implantation and was associated with 1 year mortality. Antibiotic exposure is an important risk for CDI.