Fatal Allograft Rejection and Cardiac Allograft Vasculopathy After Treatment With Pembrolizumab for Metastatic Melanoma in a Heart Transplant Recipient: A Case Report.

Checkpoint inhibitors decrease the progression of many cancers. However, the experience in immunosuppressed patients is limited, with reports of possible serious adverse events. We present a heart transplant recipient treated with pembrolizumab for metastatic melanoma who developed fatal rejection. The patient was a 29 year-old man who underwent heart transplantation at the age of 10 years for congenital heart disease. Seventeen years after transplant, he was diagnosed with scalp melanoma pT3a, N2a, M0, Stage IIIA, positive for BRAF V600E mutation treated with excision, which metastasized to his lungs and brain a year later. Dabrafenib and trametinib were started with transient response. Additional options and their risks were discussed, and pembrolizumab was started 4 months later due to the incomplete response to previous therapy. Five days after initiation the patient presented with moderate cellular rejection and possible antibody mediated rejection (ISHLT Grade 2R, pAMR 1H). Pembrolizumab was discontinued, and he was treated with steroids. Seven months later he presented in cardiogenic shock and severe coronary allograft vasculopathy. Biopsy was negative for cellular rejection, but suspicious for antibody mediated rejection (ISHLT Grade 0R, pAMR 1H), and he had a new serum alloantibody. Despite steroids and plasmapheresis he remained in refractory cardiogenic shock and died of cardiac arrest.

Impact of Ischemic Heart Failure Etiology on Cardiac Recovery During Mechanical Unloading.

BACKGROUND: Small-scale studies focused mainly on nonischemic cardiomyopathy (NICM) have shown that a subset of left ventricular assist device (LVAD) patients can achieve significant improvement of their native heart function, but the impact of ischemic cardiomyopathy (ICM) has not been specifically investigated. Many patients with acute myocardial infarction are discharged from their index hospitalization without heart failure (HF), only to return much later with overt HF syndrome, mainly caused by chronic remodeling of the noninfarcted region of the myocardium. OBJECTIVES: This study sought to prospectively investigate the effect of ICM HF etiology on LVAD-associated improvement of cardiac structure and function using NICM as control. METHODS: Consecutive patients (n = 154) with documented chronic and dilated cardiomyopathy (ICM, n = 61; NICM, n = 93) requiring durable support with continuous-flow LVAD were prospectively evaluated with serial echocardiograms and right heart catheterizations. RESULTS: In patients supported with LVAD for at least 6 months, we found that 5% of subjects with ICM and 21% of subjects with NICM achieved left ventricular ejection fraction ≥40% (p = 0.034). LV end-diastolic and end-systolic volumes and diastolic function were significantly and similarly improved in patients with ICM and NICM. CONCLUSIONS: LVAD-associated unloading for 6 months resulted in a substantial improvement in myocardial structure, and systolic and diastolic function in 1 in 20 ICM and 1 in 5 NICM patients. These specific incidence and timeline findings may provide guidance in clinical practice and research design for sequencing and prioritizing advanced HF and heart transplantation therapeutic options in patients with ICM and NICM.

Myocardial Structural and Functional Response After Long-Term Mechanical Unloading With Continuous Flow Left Ventricular Assist Device: Axial Versus Centrifugal Flow.

OBJECTIVES: The aim of this study was to assess the impact of continuous-flow left ventricular assist device (LVAD) type-axial flow (AX) versus centrifugal flow (CR)-on myocardial structural and functional response following mechanical unloading. BACKGROUND: The use of continuous-flow LVADs is increasing steadily as a therapeutic option for patients with end-stage heart failure who are not responsive to medical therapy. Whether the type of mechanical unloading influences the myocardial response is yet to be determined. METHODS: A total of 133 consecutive patients with end-stage heart failure implanted with continuous-flow LVADs (AX, n = 107 [HeartMate II Thoratec Corporation, Pleasanton, California]; CR, n = 26 [HeartWare, HeartWare International, Framingham, Massachusetts]) were prospectively studied. Echocardiograms were obtained pre-LVAD implantation and then serially at 1, 2, 3, 4, 6, 9, and 12 months post-implantation. RESULTS: The 2 pump types led to similar degrees of mechanical unloading as assessed by invasive hemodynamic status and frequency of aortic valve opening. Myocardial structural and functional parameters showed significant improvement post-LVAD in both AX and CR groups. Left ventricular ejection fraction increased significantly from a mean of 18% to 28% and 26% post-LVAD in the AX and CR groups, respectively. Left ventricular end-systolic volume index and left ventricular end-diastolic volume index decreased significantly as early as 30 days post-implantation in the 2 groups. The degree of myocardial structural or functional response between patients in the AX or CR groups appeared to be comparable. CONCLUSIONS: Long-term mechanical unloading induced by AX and CR LVADs, while operating within their routine clinical range, seems to exert comparable effects on myocardial structural and functional parameters.

Safety and efficacy of dexmedetomidine in children with heart failure.

This retrospective observational study aimed to evaluate the safety and efficacy of dexmedetomidine (DEX) for children with heart failure. The study was conducted in the cardiovascular intensive care unit (CVICU) of a single, tertiary care, academic children's hospital. A retrospective review of the charts for all children (up to 18 years of age) with signs and symptoms consistent with congestive heart failure who received DEX in our CVICU between April 2006 and April 2011 was performed. The patients were divided into two groups for study purposes: the DEX group of 21 patients, who received a DEX infusion together with other conventional sedation agents, and the control group of 23 patients, who received conventional sedation agents without the use of DEX. To evaluate the safety of DEX, physiologic data were collected including heart rate, mean arterial pressure (MAP), and inotrope score. To assess the efficacy of DEX, the amount and duration of concomitant sedation and analgesic infusions in both the DEX and control groups were examined. The numbers of rescue boluses for each category before the initiation of sedative infusion and during the sedative infusion also were examined. The baseline characteristics of the patients in the two groups were similar. There was no effect of DEX infusion on heart rate, MAP, or inotrope score at the termination of infusion. The daily amount of midazolam administered was significantly less during the last 24 h of DEX infusion in the DEX group than in the control group (p = 0.04). The daily amount of morphine infusion did not differ between the DEX and control groups during any period. The numbers of sedation and analgesic rescue boluses were lower in DEX group throughout the infusion. No other significant side effects were noted. Two patients in the DEX group had a 50 % or greater drop in MAP compared with baseline in the first 3 h after initiation of DEX infusion, whereas one patient had a 50 % or greater drop in heart rate compared with baseline in the first 3 h after initiation of DEX infusion. Administration of DEX for children with heart failure appears to be safe but should be used cautiously. Furthermore, DEX use is associated with a decreased opiate and benzodiazepine requirement for children with heart failure.

Investigating the role of metal fatigue in a case of ritleng probe fracture: its causes and prevention.

Complications with the Ritleng probe have not been reported previously. Herein, we report a case in which the Ritleng probe tip fractured during use on a patient undergoing nasolacrimal duct intubation requiring subsequent retrieval. A root-cause analysis was conducted which help to elicit possible ways to prevent such a complication in the future. Most notably the use of the stylet, documented as a cleaning device, seems to offer additional support to prevent metal fatigue and tip fracture.