Association of Amiodarone Use Prior to Orthotopic Heart Transplant with Post-Transplant Graft Dysfunction and All-Cause Mortality: A Systematic Review and Meta-Analysis.

BACKGROUND: There is conflicting data on the association between pre-orthotopic heart transplant (OHT) amiodarone use and post-OHT graft dysfunction (GD) leading to heterogeneity in clinical practice. METHODS: We performed a meta-analysis to evaluate whether pre-OHT amiodarone use was associated with meaningful increases in the incidence of GD, 30-day mortality, and 1-year mortality. Studies were identified by searching PubMed and the Cochrane Register of Clinical Trials. The Mantel-Haenszel method was used to calculate odds ratios (OR) and 95% confidence intervals (CI95) for each endpoint. RESULTS: 17 retrospective studies were identified that included 48,782 patients. 14 studies (n = 48,018) reported GD as an outcome. Pre-OHT amiodarone use was associated with increased odds of GD (OR 1.3, CI95 1.2-1.5, p < 0.001). 10 studies (n = 45,875) reported 30-day mortality based on amiodarone use. Pre-OHT amiodarone use was associated with increased odds of 30-day mortality (OR 1.4, CI95 1.2-1.5, p < 0.001). 5 studies (n = 41,404) reported 1-year mortality based on amiodarone use. Pre-OHT amiodarone use was associated with increased odds of 1-year mortality (OR 1.2, CI95 1.1-1.4, p < 0.001). The increase in absolute risk of GD, 30-day mortality, and 1-year mortality for patients with pre-OHT amiodarone use was 1.3%, 1.2%, and 1.4%, respectively. CONCLUSION: Pre-OHT amiodarone exposure was associated with increased odds of GD, 30-day mortality, and 1-year mortality. The increase in absolute risk for each endpoint was modest, and it is unclear to what extent, if any, pre-OHT amiodarone use should influence assessment of OHT candidacy.

COMPETENCE Trial: The EVAHEART 2 continuous flow left ventricular assist device.

BACKGROUND: Continuous flow left ventricular assist devices have improved outcomes in patients with end-stage heart failure that require mechanical circulatory support. Current devices have an adverse event profile that has hindered widespread application. The EVAHEART®2 left ventricular assist device (EVA2) has design features such as large blood gaps, lower pump speeds and an inflow cannula that does not protrude into the left ventricle that may mitigate the adverse events currently seen with other continuous flow devices. METHODS: A prospective, multi-center randomized non-inferiority study, COMPETENCE Trial, is underway to assess non-inferiority of the EVA2 to the HeartMate 3 LVAS when used for the treatment of refractory advanced heart failure. The primary end-point is a composite of the individual primary outcomes: Survival to cardiac transplant or device explant for recovery; Free from disabling stroke; Free from severe Right Heart Failure after implantation of original device. Randomization is in a 2:1 (EVA2:HM3) ratio. RESULTS: The first patient was enrolled into the COMPETENCE Trial in December of 2020, and 25 subjects (16 EVA2 and 9 HM3) are currently enrolled. Enrollment of a safety cohort is projected to be completed by third quarter of 2022 at which time an interim analysis will be performed. Short-term cohort (92 EVA2 subjects) and long-term cohort is expected to be completed by the end of 2023 and 2024, respectively. CONCLUSIONS: The design features of the EVA2 such as a novel inflow cannula and large blood gaps may improve clinical outcomes but require further study. The ongoing COMPETENCE trial is designed to determine if the EVA2 is non-inferior to the HM3.

Late Cardiac Tamponade 4 Years After Total Artificial Heart Implantation.

Cardiac tamponade after ventricular assist device or total artificial heart implantation can typically occur within days or weeks after surgery. This report describes the case of a woman who presented over 4 years after SynCardia 70cc total artificial heart implantation, with physiology consistent with right ventricular outflow tract obstruction. The cause was initially attributed to device membrane failure based on the device console waveform; however, during operative exploration, a large amount of proteinaceous exudate was surrounding the device and causing the obstruction. This report illustrates how tamponade can result years after device implantation, secondary to porosity of the outflow grafts.

Postoperative chemotherapy and radiation improve survival following cardiac sarcoma resection.

OBJECTIVE: Cardiac sarcoma represents a rare and aggressive form of cancer with a paucity of data to produce outcome-driven evidence-based guidelines. Current surgical management consists of resection with postoperative therapy (chemotherapy, radiation, or both) offered on a selective, individualized basis. This study was designed to determine whether postoperative therapy was associated with improved overall survival after resection. METHODS: The National Cancer Database was used to identify patients with cardiac sarcoma between 2004 and 2015. Patient characteristics were stratified by treatment (surgical, nonsurgical, and none), and treatment was analyzed by stage. Overall survival, assessed with Kaplan-Meier methodology, was compared between patients who received postoperative therapy and those who did not following resection. Multivariable survival modeling using a Weibull model identified risk factors associated with survival while controlling for confounders. RESULTS: The study included 617 patients diagnosed with cardiac sarcoma. Only 24% (149/617) of patients were diagnosed with early-stage disease. Angiosarcoma represented 48% (298/617) of cases and was the most commonly identified histologic subtype. 60% (372/617) underwent surgical resection and 58% (216/372) of those patients were treated with postoperative therapy. Following surgery, median survival was more than doubled for patients treated with postoperative therapy (19 months vs 8 months, P = .026). However, 5-year overall survival was similar between the groups. Multivariable analysis confirmed an improvement in survival with postoperative therapy (hazard ratio, 0.68; 95% confidence interval, 0.51-0.91, P = .009). CONCLUSIONS: Postoperative therapy is associated with better median survival following resection of cardiac sarcoma. However, at 5 years, the difference in overall survival is not statistically significant.

Predictors for acute and chronic renal failure and survival in patients supported with veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: Renal failure is a common occurrence in patients with refractory cardiogenic shock including those supported with veno-arterial extracorporeal membrane oxygenation. Prevalence and outcome of acute and chronic kidney failure in extracorporeal membrane oxygenation patients have not been well documented. In this study, we investigated the occurrence of acute and chronic kidney failure in veno-arterial extracorporeal membrane oxygenation patients as well as predictors for survival. METHODS: This is a single center retrospective clinical study. We included adult patients with refractory cardiogenic shock who were supported by veno-arterial extracorporeal membrane oxygenation between 2008 and 2015. The primary endpoint of the study was acute kidney injury (KDIGO Stage 3) during extracorporeal membrane oxygenation and chronic kidney failure requiring renal replacement therapy, 30 and 90 days after extracorporeal membrane oxygenation. The secondary endpoint was in-hospital survival and 90-day survival. RESULTS: A total of 196 veno-arterial extracorporeal membrane oxygenation patients were investigated. In total, 41.8% (82/196) patients had acute renal failure requiring continuous renal replacement therapy during extracorporeal membrane oxygenation. The 30- and 90-day survival was 55.1% (108/196) and 48.5% (95/196), respectively; 21.3% (23/108) and 11.6% (11/95) patients needed renal replacement therapy after 30 and 90 days, respectively. Predictors for KDIGO Stage 3 renal failure during extracorporeal membrane oxygenation were lactate (p = 0.026) and the number of blood units transfused during extracorporeal membrane oxygenation support (p = 0.000). A predictor for renal replacement therapy after 30 and 90 days was an elevated plasma-free hemoglobin level. The in-hospital survival was 54.6% (107/196). Serum lactate of less than 4.3 mmol/L, lower age, plasma-free hemoglobin of ⩽62 mg/dL, low number of blood units transfused during extracorporeal membrane oxygenation, and the use of an intra-aortic balloon pump were predictors for in-hospital and 90-day survival.

Current Role of the Total Artificial Heart in the Management of Advanced Heart Failure.

The total artificial heart (TAH) is a form of mechanical circulatory support that involves resection of the native ventricles followed by placement of a device that can restore total pulmonary and systemic flow. Given the increasing burden of congestive heart failure and cardiovascular disease, the number of people in need of cardiac replacement therapy will continue to grow. Despite aggressive efforts to expand the donor pool, the number of heart transplants in the United States (US) has plateaued at less than 3000 per year. In addition, there is increasing recognition of the long-term complications of current generation left ventricular assist devices such as progressive aortic insufficiency, complications related to blood trauma, and both early and delayed right ventricular failure. These factors may serve to expand the role of the TAH in the treatment of patients with end-stage heart failure particularly if new generation devices are developed that are durable, have an improved safety profile, and are totally implantable. PURPOSE OF REVIEW: To review the role and current evidence of the use of the TAH in the management of advanced heart failure and discuss development of recent TAHs that may have an impact on the field in the near future. RECENT FINDINGS: Many patients that receive a heart transplant are bridged with a mechanical support device, most commonly a left ventricular assist device (LVAD). However, there is a small subset of patients with profound biventricular (BV) failure or structural abnormalities that preclude LVAD placement, who will require support with a biventricular assist device (BiVAD) or TAH. There are numerous studies showing the efficacy of the TAH in bridging to transplantation. Also, recent studies have shown equal rates of bridging to transplantation between patients receiving a TAH compared to a BiVAD. However, BiVAD support has a higher incidence of stroke in addition to complications related to the native heart such as arrhythmias and valve dysfunction. Currently, there are multiple new generation artificial hearts in both preclinical development and in clinical trials for both bridge to transplant and destination therapy. TAH have been shown to be effective for circulatory support in select patients with end-stage heart failure. Current LVADs are associated with significant long-term complications related to retention of the native heart and pump design. Many of these complications may be addressed by the increased use of cardiac replacement therapy, i.e., total artificial hearts. Multiple generations of both pulsatile and advanced design continuous flow TAH are under development which have the potential to expand the role of TAHs.

Clinical Experience of HeartMate II to HeartWare Left Ventricular Assist Device Exchange: A Multicenter Experience.

BACKGROUND: Despite improvements in pump design and durability, left ventricular assist device patients still suffer from life-threatening complications such as pump thrombosis (PT) and infection, often necessitating device exchange. Surgical exchange from HeartMate II (HM2; Abbott, Pleasanton, CA) to another HM2 is safe and associated with low mortality, but recurrent device thrombosis rates are high. Switching from axial-flow to centrifugal-flow pump, such as the HeartWare ventricular assist device (HVAD; Medtronic, Framingham, MA) may offer certain advantages due to it being a smaller, newer generation device, although there are limited data to support this strategy. Herein, we aimed to assess the surgical approach and feasibility, safety, and outcomes of surgical exchange from HM2 to HVAD. METHODS: We evaluated HM2 patients who underwent device exchange to HVAD due to PT or infection at 4 large-volume left ventricular assist device implant centers. RESULTS: Twenty-four patients underwent HM2 to HVAD exchange due to PT (92%) and refractory infection (8%). Patients were male (75%), white (88%), with ischemic cardiomyopathy (54%), Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) scale level 1-3 (90%), and destination therapy (62%). The majority underwent redo-sternotomy (79%) and the remainder underwent minimally invasive thoracotomy with subcostal approach. The existing HM2 outflow graft was maintained in 79% of cases. Recurrent PT was noted in 9% of patients. Mortality was 8% at 30 days and 33% at 1 year. CONCLUSIONS: The surgical exchange from a HM2 to HVAD is safe and feasible, despite the differences in device specifications and surgical adaptation required. Newer-generation pumps are increasingly considered for exchange in the setting of HM2 device complication, and increasing experience with modified surgical approaches may be valuable in the current era.

Heparin-induced thrombocytopenia in patients on extracorporeal membrane oxygenation and the role of a heparin-bonded circuit.

BACKGROUND: In patients supported with extracorporeal membrane oxygenation, and who develop heparin-induced thrombocytopenia, there is no clear evidence to support changing to a non-heparin-coated extracorporeal membrane oxygenation circuit. Our goal was to evaluate clinical outcomes of patients who were continued on heparin-bonded circuits despite diagnosed heparin-induced thrombocytopenia. METHODS: We completed a single-center retrospective study of all patients who underwent extracorporeal membrane oxygenation support from July 2008 to July 2017 and were tested heparin-induced thrombocytopenia positive while on extracorporeal membrane oxygenation support. After diagnosis of heparin-induced thrombocytopenia, mean platelet count (k/µL) was measured on consecutive days for 14 days. RESULTS: Out of 455 patients, 14 (3.1%) had a diagnosis of heparin-induced thrombocytopenia by serotonin release assay and systemic heparin treatment was discontinued in every case. In total, 11 of the heparin-induced thrombocytopenia patients (78.6%) survived to discharge. The overall survival of all 455 extracorporeal membrane oxygenation patients was 54.1%. Platelets counts after discontinuation of systemic heparin in the heparin-induced thrombocytopenia patients increased from a mean of 59.8 k/µL at time of heparin-induced thrombocytopenia diagnosis to a mean of 280.2 k/µL at 14 days after discontinuation of heparin despite continuation of the heparin-bonded circuit. Platelet count increased in heparin-induced thrombocytopenia patients on extracorporeal membrane oxygenation support after discontinuation of systemic heparin even if maintained on the heparin-bonded circuit. CONCLUSION: Discontinuation of systemic heparin but continuation of heparin-coated extracorporeal membrane oxygenation circuits appeared to be an appropriate response for our extracorporeal membrane oxygenation-supported patients who developed heparin-induced thrombocytopenia. Survival in this group was not significantly different to those patients on extracorporeal membrane oxygenation without heparin-induced thrombocytopenia. Larger studies should evaluate the safety of heparin-bonded extracorporeal membrane oxygenation systems in heparin-induced thrombocytopenia patients.

Pressure Support Breaths Triggered by Total Artificial Heart in Invasive and Non-Invasive Mechanical Ventilation.

Because of the risks associated with extended mechanical ventilation, it is desirable to extubate patients as early as possible. However, weaning patients from mechanical ventilation too early has risks associated with it as well. Thus, it is important to note that in the two cases presented here, pressure-supported breaths were falsely triggered by a patient's a Syncardia® total artificial heart (TAH), influencing decisions about weaning the patient from mechanical ventilation.

Controversies and Challenges of Ventricular Assist Device Therapy.

Left ventricular assist device (LVAD) therapy has emerged as an increasingly vital facet of the treatment algorithm for advanced heart failure. Growing experience with LVAD support has led to substantial improvements in outcomes, with 1-year survival rates approaching that of cardiac transplantation. These therapeutic refinements have engendered growing interests in the potential for expanding the clinical indications for LVAD therapy to patients with less advanced heart failure. The primary obstacles to this evolution of care center largely on the prevention and/or management of the adverse events associated with LVAD therapy along with patient preference. Many programs also face the mounting difficulty of balancing quality outcomes with the increased volume of implants. During the recently assembled Users Meeting organized by St. Jude Medical, heart failure clinicians from nearly 50 LVAD implanting centers discussed these and other challenges and controversies impacting the field. The present review summarizes the key insights gleaned from this meeting.

Predicting Survival in Patients Treated With Extracorporeal Membrane Oxygenation After Myocardial Infarction.

OBJECTIVES: Acute myocardial infarction is the most common cause of cardiogenic shock. Although the number of patients with acute myocardial infarction complicated by cardiogenic shock who were treated with venoarterial extracorporeal membrane oxygenation increased during the last decade, detailed data on survival are lacking. We sought to analyze covariates that were independently associated with survival in this patient population and to externally validate the newly developed prEdictioN of Cardiogenic shock OUtcome foR Acute myocardial infarction patients salvaGed by venoarterial Extracorporeal membrane oxygenation (ENCOURAGE) score. DESIGN: Retrospective clinical study. SETTING: A single academic teaching hospital. PATIENTS: Adult patients with acute myocardial infarction complicated by cardiogenic shock who were supported by venoarterial extracorporeal membrane oxygenation from June 2008 to September 2016. INTERVENTIONS: Fourteen individual variables were assessed for their association with the primary endpoint. These variables were prespecified by the study team as being the most likely to affect survival. A receiver operating characteristic analysis was also performed to test the ability of the ENCOURAGE score to predict survival in this patient cohort. MEASUREMENTS AND MAIN RESULTS: The primary endpoint of the study was in-hospital survival. A total of 61 patients were included in the analysis. Thirty-seven (60.7%) could be weaned from venoarterial extracorporeal membrane oxygenation and 36 (59.0%) survived. Survival was significantly higher in patients less than 65 years old (odds ratio, 14.6 [CI, 2.5-84.0]; p = 0.003), whose body mass index was less than 32 kg/m (odds ratio, 5.5 [CI, 1.2-25.4]; p = 0.029) and international normalized ratio was less than 2 (odds ratio, 7.3 [CI, 1.3-40.1]; p = 0.022). In patients where the first lactate drawn was less than 3 mmol/L, the survival was not significantly higher (odds ratio, 4.4 [CI, 0.6-32.6]; p = 0.147). The C-statistic for predicting survival using a modified version of the ENCOURAGE score, which replaced prothrombin activity less than 50% with an international normalized ratio greater than 2, was 0.74 (95% CI, 0.61-0.87). CONCLUSIONS: In this single-center study, several important covariates were associated with improved survival in patients with acute myocardial infarction complicated by cardiogenic shock who were supported by venoarterial extracorporeal membrane oxygenation and the ENCOURAGE score was found to be externally valid for predicting survival to hospital discharge.

Long-Term Survival in Patients Receiving a Continuous-Flow Left Ventricular Assist Device.

BACKGROUND: Long-term survivors after implantation of left ventricular assist devices (LVADs) are increasing in prevalence. We describe the characteristics and outcomes in patients surviving longer than 4 years on LVAD support. METHODS: We performed a multicenter, retrospective analysis of patients surviving at least 4 years on continuous-flow LVAD (CF-LVAD) support with a HeartMate II at centers participating in the Evolving Mechanical support Research Group. RESULTS: Between 2005 and 2010, 156 long-term survivors were identified with a mean survival of 7.1 years (95% confidence interval: 6.7 to 7.5 years). The mean age was 58.2 ± 15.2 years and 30.1% were women. Readmission rate was low at 1.1 events per patient per year with the most common reasons leading to readmission being infection (0.10 readmissions per patient per year) and gastrointestinal bleeding (0.07 readmissions per patient per year). Two years after implantation, 97% of patients were either New York Heart Association functional class I or II, with 92% at 4 years. CONCLUSIONS: Patients surviving 4 years on CF-LVAD support can anticipate ongoing long-term survival with sustained improvements in functionality and low rates of rehospitalization.