Initiation of Neurohormonal Blockade and Clinical Outcomes in HeartMate 3 LVAD Recipients During Index Implantation.

Background The use of neurohormonal blockade (NB) including beta blockers, renin angiotensin inhibitors (RASIs), and mineralocorticoid receptor antagonists (MRAs) in patients after left ventricular assist device (LVAD) implantation has been associated with improved clinical outcomes. However, its use during and soon after index discharge (LVAD implant admission), a period of potential hemodynamic and laboratory vulnerability, and impact on outcomes in HeartMate 3 (HM3) recipients remains undefined. Purpose This study aimed to characterize index HeartMate 3 (HM3) LVAD recipients who were given a prescription for NB at discharge and determine its clinical impact. Methods A single-center retrospective analysis was performed of patients who underwent HM3 LVAD implantation from January 1, 2015, to December 31, 2021. To align with contemporary definitions, we included sodium-glucose cotransporter 2 inhibitors (SGLT-2i) in the NB cohort. Patients on and not on any NB after index discharge were compared. Cox proportional hazards modeling was performed to investigate the association between the presence of NB with survival and heart failure (HF) readmission. Results 273 patients underwent HM3 implantation during the study period. The average implant age was 58 years, 75% were men, and 78% were Black patients. Of the 273 patients, 138 (50%) had a prescription of at least one NB agent after index discharge. RASIs were the most prescribed after index discharge (42%), followed by MRAs (17%), beta blockers (3.7%), and SGLT-2i (3.3%) (Table). Predictors of NB use include discharge creatinine (HR 0.5; 95% CI, 0.28 - 0.92; p=0.026), hemoglobin (HR 1.33; 95% CI, 1.06 - 1.67; p=0.012) and history of stroke (HR 0.42; 95% CI, 0.21 - 0.88; p=0.021). Patients who received NB at index discharge had longer survival compared to those who did not at a median follow-up of 3.8 years (Figure). Multivariate adjustment demonstrated a trend towards a lower risk of mortality in HM3 LVAD recipients who received NB at discharge (HR 0.69; 95% CI, 0.44-1.09; p=0.11). A discharge prescription for NB was not associated with HF readmission. Conclusion Implementation of NB remains an opportunity for improvement in the care of HM3 LVAD recipients. Our findings suggest that despite the concerns of labile changes in clinical status, early initiation of NB appears to have a beneficial signal, acknowledging that there may be clinical factors that influence initiation of NB that are also prognostic. Further studies are needed to examine whether an aggressive, upfront implementation of NB during index hospitalization will improve clinical outcomes.Table.Baseline Characteristics Figure.Kaplan-Meier survival analysis

Background: Despite the survival benefit of durable left ventricular assist device (LVAD) therapy in patients with advanced heart failure, hospital readmissions due to heart failure (HF) remain a significant morbidity and determinant of quality of life. Objective: This study aimed to characterize patients with and without a HF readmission and determine its clinical impact following HeartMate 3 (HM3) LVAD implantation. Methods/Approach: A single-center retrospective analysis was performed of patients who underwent HM3 LVAD implantation from January 1, 2015 to December 31, 2021. Patients with and without a HF readmission were compared based on 53 variables. Cox proportional hazard model was performed to investigate the association between HF readmission and survival. Results: A total of 273 patients underwent HM3 implantation. The average implant age was 58 years, 75% were men, and 78% were Black patients. Of the 273 patients, 78 (29%) had a HF readmission and 58 (74%) occurred within the first year following implant. Predictors of a HF readmission include pre-implant diabetes mellitus (HR 1.96; 95% CI, 1.2-3.2; p=0.007), pre-implant body mass index (HR 1.05; 95% CI, 1.02-1.09; p<0.001) and post implant BUN (HR 1.02; 95% CI, 1-1.04; p=0.018). There was no significant difference in survival in patients with and without a HF readmission (multivariate-adjusted HR 1.44; 95% CI, 0.87-2.37; p=0.153; Figure) at long-term follow up (6 years). Conclusion: Readmissions for HF remain an opportunity for improvement in the care of HM3 LVAD patients. However, a HF readmission was not associated with an increased risk of death. Addressing comorbid conditions and identifying strategies to optimize LVAD and HF management in this high-risk cohort warrant further exploration to improve clinical outcomes.

Background: Despite the survival benefit of durable left ventricular assist devices (LVAD) in patients with end stage heart failure, right ventricular failure (RVF) remains a prominent cause of morbidity and mortality. It remains unclear if the development of early RVF after LVAD implantation, a period of hemodynamic variability, adversely impacts long-term outcomes in the HeartMate 3 (HM3) population. Purpose: This study aimed to characterize HM3 LVAD recipients who developed early RVF and determine its clinical impact. Methods: A single-center retrospective analysis was performed of patients who underwent HM3 LVAD implantation from January 1, 2015, to December 31, 2021. Early RVF was defined as perioperative use of intravenous inotropic support ≥ 14 days or right ventricular assist device (RVAD) placement after LVAD implantation. Patients with and without RVF during index admission were compared. Cox proportional hazards modeling was performed to investigate the association between the presence of RVF with survival and heart failure (HF) readmission. Results: 273 patients underwent HM3 implantation during the study period. The average implant age was 58 years, 75% were men, and 78% were Black patients. Of the 273 patients, 145 (53%) had early RVF after LVAD implantation. History of hypertension was a predictor of early RVF (HR 1.75; 95% CI, 1- 3.05; p=0.049). There was no significant difference in survival in patients with and without early RVF (multivariate-adjusted HR 1.32; 95% CI, 0.85-2.05; p=0.215; Figure) at 6 years (median 3.8 years) of follow-up. Early RVF at index admission was also not associated with subsequent HF readmission (multivariate-adjusted HR 0.87; 95% CI, 0.56-1.35; p=0.542). Conclusion: Our findings suggest that despite early RVF during index HM3 LVAD implantation, there was no association with long term clinical outcomes. Future studies should focus on hemodynamic and clinical optimization of this population during the perioperative period to potentially reduce subsequent adverse events after hospital discharge.

Hyponatremia is Associated with Poor Prognosis in Left Ventricular Assist Device Patients

Adverse Events During Hemodialysis in LVAD Recipients

In this issue of Circulation, Birks et al 1 report their recent experience using the combination of continuous-flow (CF) circulatory support and pharmacological therapy to treat advanced heart failure in patients requiring left ventricular assist device (LVAD) support. Thirty-three patients underwent HeartMate II (HMII) LVAD implantation at Harefield hospital during the 3-year study period. Twenty-three patients (70%) with nonischemic cardiomyopathy were considered appropriate for the recovery protocol at the time of HMII LVAD implantation, and 20 patients (61%) who survived LVAD implantation formed the study cohort. With their strategy of aggressive neurohormonal blockade (phase I) followed by high-dose clenbuterol (phase II), 12 (60%) of the study cohort met criteria for LVAD explantation, and all 10 (50%) who survived the perioperative period demonstrated sustained recovery over 56 to 1112 days of follow-up. Therefore, 30% of all patients and 43% of all nonischemic patients undergoing HMII implantation could be managed to long-lasting recovery. In an era in which transplant waiting times have blurred the distinction between bridge-totransplant and destination therapy for some patients, this single-center experience is intriguing and offers hope for a new strategy for select patients supported with CF LVADs. Article see p 381 Reports in the literature regarding rates of cardiac recovery during pulsatile LVAD support are quite varied (Table 1). The Columbia University group reported a 1% rate of sustained cardiac recovery in 111 patients with both ischemic and nonischemic etiology of heart failure. 2 In contrast, the German Heart Institute reported that 13% of patients with nonischemic heart failure demonstrated sustained recovery (minimum follow-up of 36 months) after LVAD explantation. 3 The LVAD Working Group was the first multicenter, prospective initiative to study recovery.4 Sixty-seven LVAD patients (only 1 CF LVAD) with both ischemic and nonischemic causes underwent serial echocardiograms at reduced flow to seek recovery. Six percent of the whole cohort and 7% of all nonischemic patients could undergo LVAD explantation. None of these reports described the consistent use of pharmacological therapy during LVAD support, and it was not until the first Harefield recovery study 5 that data regarding combined pharmacological and mechanical support were available. In the first Harefield study, 15 LVAD patients (1 CF LVAD) received maximal doses of heart failure medications, followed by high-dose clenbuterol. All patients had a nonischemic etiology, and most (80%) had heart failure for 6 months. The authors reported that 75% of patients receiving clenbuterol could undergo LVAD explantation and 46% of all patients with nonischemic heart failure presenting for LVAD could be managed successfully to recovery in this way. These data from Harefield represented the most successful reported recovery strategy to date, and prompted a multicenter study in the United States (to replicate the Harefield recovery protocol) called the Harefield Recovery Protocol Study (HARPS). HARPS has now completed enrollment of 17 patients with the HMI pulsatile LVAD, 13 of whom received both maximal neurohormonal blockade and high-dose clenbuterol. Results from the US HARPS study will be presented in the near future. With the approval of the HMII LVAD for both bridge-to

Over the last 2 decades, numerous advancements in medical therapies have improved patient outcomes in heart failure (HF). However, a significant number of patients still progress to end-stage HF, in which treatment options are largely limited to cardiac transplantation. As patient demands for transplant continue to exceed the supply of available organs, mechanical assist devices—specifically, the left ventricular assist device (LVAD)—were initially introduced as a bridge to cardiac transplantation. LVADs have 2 important beneficial effects. First, LVADs are placed in parallel to the native left ventricle (LV), causing pressure and volume unloading of the LV. Second, LVADs restore cardiac output and subsequent perfusion to the organs. As a result of these 2 effects, it became evident that some patients had actual improvement in LV function after LVAD placement. The term reverse remodeling was used to describe the improvement in myocardial function that was observed in patients with a seemingly end-stage disease. With reverse remodeling, a new hope for the treatment of HF was born—using LVADs as a bridge to recovery; however, to date, this promise has largely been unrealized. This probably is reflective of the fact that the sequela of mechanical ventricular unloading are quite complex and appear to involve the engagement of competing biological pathways including regression of cardiomyocyte hypertrophy as well as progressive cell atrophy. Although the promise of ventricular recovery still persists, its actualization will await a more comprehensive dissection of these competing biological processes. This review will discuss the beneficial clinical effects of LVAD support as well as review what is known about the cellular and molecular response to mechanical unloading and mechanisms of reverse remodeling. Key research findings have been summarized in the Table. View this table: Table. Summary of Research of LVAD Support on Clinical Effects and the Cellular and Molecular Changes That May Contribute to Reverse …

Left Ventricular Assist Devices and Renal Ramifications.

Prognostic Impact of Implantable Cardioverter Defibrillators in Patients with Continuous Flow Left Ventricular Assist Devices

Cannula position in HeartMate II and HeartWare left ventricular assist devices (LVADs) is associated with clinical outcome. This study aimed to investigate the clinical implication of the device positioning in HeartMate 3 LVAD cohort. Consecutive patients who underwent HeartMate 3 LVAD implantation were followed for one year from index discharge. At index discharge, chest X-ray parameters were measured: (a) cannula coronal angle, (b) height of pump bottom, (c) cannula sagittal angle, and (d) cannula lumen area. The association of each measurement of cannula position with one-year clinical outcomes was investigated. Sixty-four HeartMate 3 LVAD patients (58 years old, 64% male) were enrolled. In the multivariable Cox regression model, the cannula coronal angle was a significant predictor of death or heart failure readmission (hazard ratio 1.27 [1.01-1.60], P = .045). Patients with a cannula coronal angle ≤28° had lower central venous pressure (P = .030), lower pulmonary capillary wedge pressure (P = .027), and smaller left ventricular size (P = .019) compared to those with the angle >28°. Right ventricular size and parameters of right ventricular function were also better in the narrow angle group, as was one-year cumulative incidence of death or heart failure readmission (10% vs. 50%, P = .008). Narrow cannula coronal angle in patients with HeartMate 3 LVADs was associated with improved cardiac unloading and lower incidence of death or heart failure readmission. Larger studies to confirm the implication of optimal device positioning are warranted.

Aortic regurgitation during continuous-flow left ventricular assist device support: An insufficient understanding of an insufficient lesion

Left ventricular assist devices (LVADs) are utilized as a therapeutic option for patients with end-stage heart failure. While LVAD implantation can enhance survival rates and quality of life, the procedure has its risks, and postoperative complications are common. This review aims to investigate whether there is an association between living in a rural area and the incidence of postoperative complications or hospital readmissions following LVAD implantation, compared to urban LVAD recipients. A comprehensive literature review examined studies that compared postoperative outcomes between rural and urban LVAD recipients. Data on adverse events, hospitalizations, and mortality rates were extracted, focusing on the impact of geographic location on these outcomes. The review found that rural LVAD recipients may be at a higher risk for certain complications, including gastrointestinal bleeding, ventricular arrhythmias, LVAD complications, and stroke. Rural patients also exhibited higher instances of emergency department visits and hospital readmissions. Despite these challenges, survival rates and heart transplantation outcomes at 1 year were similar between rural and urban recipients. However, rural patients exhibited a higher driveline infection rate at 1 year. The findings of this review suggest that rural residency may be associated with an increased risk of certain postoperative complications and hospital readmissions following LVAD implantation. These results highlight the need for healthcare strategies to address the challenges faced by rural LVAD recipients. Further research is necessary to understand the relationship between geographic location and LVAD outcomes and to develop interventions that can improve postoperative care for this vulnerable population.

Background: Left ventricular assist devices (LVADs) are utilized as a therapeutic option for patients with end-stage heart failure. While LVAD implantation can significantly improve survival rates and quality of life, the procedure is not without risks, and postoperative complications are common. This review aims to investigate whether there is an association between living in a rural area and the incidence of postoperative complications or hospital readmissions following LVAD implantation, compared to urban LVAD recipients. Methods: A comprehensive review of the literature was conducted, examining studies that compared postoperative outcomes between rural and urban LVAD recipients. Data were extracted on adverse events, hospitalizations, and mortality rates, with a focus on the impact of geographic location on these outcomes. Results: The review found that rural LVAD recipients may be at a higher risk for certain postoperative complications, such as gastrointestinal bleeding, ventricular arrhythmias, LVAD complications, and stroke. Rural patients also had higher instances of emergency department visits and hospital readmissions. Despite these challenges, survival rates and heart transplantation outcomes at 1 year were similar between rural and urban recipients. However, rural patients exhibited a higher driveline infection rate at 1 year. Conclusion: The findings of this review suggest that rural residency may be associated with an increased risk of certain postoperative complications and hospital readmissions following LVAD implantation. These results highlight the need for tailored healthcare strategies to address the unique challenges faced by rural LVAD recipients. Further research is necessary to fully understand the relationship between geographic location and LVAD outcomes, and to develop interventions that can improve postoperative care for this vulnerable population

If it ain't broken, don't fix it (but if it is, make sure you know): aortic valve interventions during left ventricular assist device implantation.

Axial-flow LVADs have become an integral tool in the management of end-stage heart failure. Consequently, nonsurgical bleeding has emerged as a major source of morbidity and mortality in this fragile population. The mechanisms responsible for these adverse events include acquired von Willebrand disease, GI tract angiodysplasia formation, impaired platelet aggregation, and overuse of anticoagulation therapy. Because of ongoing concerns for pump thrombosis and thromboembolic events, the thrombotic/bleeding paradigm has led to a difficult clinical dilemma for those managing patients treated with axial flow LVADs. As the field progresses, advances in the understanding of the pathological mechanisms underlying bleeding/thrombosis risk, careful risk stratification, and potential use of novel anticoagulants will all play a role in the management of the LVAD patient.