Three-year outcomes of de novo tacrolimus extended-release tablets (LCPT) compared to twice-daily tacrolimus in adult heart transplantation.

BACKGROUND: Extended-release tacrolimus for prophylaxis of allograft rejection in heart transplant (HT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release (IR-) tacrolimus. We compared long-term efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. METHODS: 25 prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 3 years following transplant was compared between groups using non-inferiority analysis. RESULTS: LCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 16% (90%CI, -37%, -1%, non-inferiority p = 0.002) up to 3 years following heart transplant. Up to 3-years post-transplant, 14 patients remained on once-daily LCPT and 10 patients were switched to IR-tacrolimus due to lack of insurance coverage. There were no significant differences in the rate of chronic kidney disease requiring dialysis, cytomegalovirus requiring treatment, cardiac allograft vasculopathy, and malignancy within 3 years following transplant. CONCLUSION: LCPT is non-inferior in efficacy to IR-tacrolimus in heart transplantation with a similar safety profile. Narrowly-constrained FDA labels specific to kidney transplant remain a barrier to consistent access to many immunosuppressant medications for recipients of non-kidney solid organs. We recommend the FDA consider developing facile pathways for expanding the approved label of extended-release tacrolimus formulations to heart transplant recipients.

Importance of right heart catheterization in advanced heart failure management.

Patients with chronic congestive heart failure belong to a population with reduced quality of life, poor functional class, and increased risk of mortality and morbidity. In these patients, assessment of invasive hemodynamics both serves therapeutic purposes and is useful for stratification roles. The right heart catheterization has become a cornerstone diagnostic tool for patients in refractory heart failure or cardiogenic shock, as well as for the assessment of candidacy for heart replacement therapies, and the management of patients following mechanical circulatory assist device implantation and heart transplantation.

De novo tacrolimus extended-release tablets (LCPT) versus twice-daily tacrolimus in adult heart transplantation: Results of a single-center non-inferiority matched control trial.

Extended-release tacrolimus for prophylaxis of allograft rejection in orthotopic heart transplant (OHT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release tacrolimus (IR-tacrolimus). We compared the efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. Twenty-five prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 1 year was compared using non-inferiority analysis. LCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 20% (90% CI: -40%, -.5%; non-inferiority P = .001). Tacrolimus trough levels peaked at 2-3 months and were higher in LCPT (median 14.5 vs. 12.7 ng/ml; P = .03) with similar dose levels (LCPT vs. IR-tacrolimus: .08 vs. .09 mg/kg/day; P = .33). Cardiovascular-related readmissions were reduced by 62% (P = .046) in LCPT patients. The complication rate per transplant admission and all-cause readmission rate did not differ significantly. These results suggest that LCPT is non-inferior in efficacy to IR-tacrolimus with a similar safety profile and improved bioavailability in OHT.

Cardiogenic Shock in Patients with Advanced Chronic Heart Failure.

Patients with end-stage heart failure (HF) who have failed optimal medical therapy provide a unique set of challenges compared to the more prevalent population of patients with cardiogenic shock (CS) due to ST-segment elevation myocardial infarction. Progression from "preshock" into a refractory state of CS is associated with a dismal outcome due to difficulties with the patient's recognition, response to interventions, and candidacy for salvage options. Challenges include heterogeneity of CS (eg, different phenotypes, etiologies, duration, acuity of onset, hemodynamics, end-organ effects), lack of a universal definition of CS that is applicable to this patient population, and blunted hemodynamic response given the patient's prolonged compensatory state. Individuals with advanced HF in CS require a multidisciplinary team-based assessment regarding when to escalate from medical therapy into temporary mechanical circulatory support, and they need an eligibility evaluation to determine their candidacy for advanced therapy. In this review, we discuss the definition and clinical phenotypes of CS, classification of CS in advanced HF patients, the utility of temporary mechanical circulatory support, and the role of the CS team.

Acute Isolated Coronary Artery Dissection Causing Massive Acute Myocardial Infarction and Leading to Unsuccessful Coronary Bypass, Extracorporeal Life Support, and Successful Cardiac Transplantation.

Described herein is a 42-year-old woman who suddenly developed a spontaneous isolated coronary arterial dissection which led to massive acute myocardial infarction with shock, unsuccessful coronary artery bypass grafting, transiently successful extracorporeal life support, and finally successful heart transplant. Such a sequence of events is exceedingly rare for patients with coronary dissection and prompted this report.

Cardiac catheterization and percutaneous intervention procedures on extracorporeal membrane oxygenation support.

Extracorporeal membrane oxygenation (ECMO) is used to support critically ill patients when conventional therapies have failed. ECMO has been available for four decades and has gained use as a rescue therapy in severe refractory hypoxic disorders and in patients with refractory cardiogenic shock (RCS). Over recent years, several percutaneous cardiac interventions and implant devices have been developed that are now used frequently in conjunction with ECMO in order to maintain organ perfusion. Here, we review the literature on VA-ECMO cannulation location, the use of VA-ECMO in interventions (e.g., coronary interventions and structural heart interventions) and percutaneous cardiac device implantation in VA-ECMO recipients with RCS.