Nilamkumar Patel

Incidence, Risk Factors, and Clinical Outcomes of Atrial Fibrillation and Atrial Flutter After Heart Transplantation

Atrial fibrillation (AF) and atrial flutter (AFL) after heart transplantation (HT) has been associated with increased mortality. Diverse incidence rates have been reported to date, with no clear classification according to the time of onset of such arrhythmias. We determined the incidence of AF/AFL using the time of onset after HT and analyzed the associated risk factors and outcomes. We performed a retrospective study of 228 HT recipients (March 1996 to July 2007), including donor and recipient demographics, gender mismatch, ischemia time, surgical anastomosis, time of onset of AF/AFL, acute cellular rejection, left ventricular systolic function, and all-cause mortality. The mean age of the donors (81% men) was 30 +/- 12 years and of the recipients (78% men) was 53 +/- 11 years. AF/AFL occurred in 45 patients (20%): 24 (11%) in the first 30 days, 10 (4%) within the 31 days to 1 year, and 11 (5%) after 1 year. When the patients with AF/AFL were compared to those with sinus rhythm, the significant difference was the older mean age of the donors (p = 0.001) and the recipients (p = 0.02). The all-cause mortality rate was 43% for those with AF/AFL compared to 23% for those with sinus rhythm (hazard ratio 2.45; 95% confidence interval 1.2 to 4.8), mostly driven by the greater mortality in the later-onset AF/AFL group (>30 days after HT). In conclusion, AF and AFL have an incidence of 20% after HT and are associated with increased overall mortality compared to that in patients in sinus rhythm. AF/AFL is more common within the first 30 days of HT, with an overall incidence of 20%. Older donor and recipient age is a risk factor associated with AF/AFL.

Thymidine kinase and mtDNA depletion in human cardiomyopathy: epigenetic and translational evidence for energy starvation.

This study addresses how depletion of human cardiac left ventricle (LV) mitochondrial DNA (mtDNA) and epigenetic nuclear DNA methylation promote cardiac dysfunction in human dilated cardiomyopathy (DCM) through regulation of pyrimidine nucleotide kinases. Samples of DCM LV and right ventricle (n = 18) were obtained fresh at heart transplant surgery. Parallel samples from nonfailing (NF) controls (n = 12) were from donor hearts found unsuitable for clinical use. We analyzed abundance of mtDNA and nuclear DNA (nDNA) using qPCR. LV mtDNA was depleted in DCM (50%, P < 0.05 each) compared with NF. No detectable change in RV mtDNA abundance occurred. DNA methylation and gene expression were determined using microarray analysis (GEO accession number: GSE43435). Fifty-seven gene promoters exhibited DNA hypermethylation or hypomethylation in DCM LVs. Among those, cytosolic thymidine kinase 1 (TK1) was hypermethylated. Expression arrays revealed decreased abundance of the TK1 mRNA transcript with no change in transcripts for other relevant thymidine metabolism enzymes. Quantitative immunoblots confirmed decreased TK1 polypeptide steady state abundance. TK1 activity remained unchanged in DCM samples while mitochondrial thymidine kinase (TK2) activity was significantly reduced. Compensatory TK activity was found in cardiac myocytes in the DCM LV. Diminished TK2 activity is mechanistically important to reduced mtDNA abundance and identified in DCM LV samples here. Epigenetic and genetic changes result in changes in mtDNA and in nucleotide substrates for mtDNA replication and underpin energy starvation in DCM.

Utility of screening computed tomography of chest, abdomen and pelvis in patients after heart transplantation

INTRODUCTION Malignancy is a late cause of mortality in heart transplant recipients. It is unknown if screening computed tomography scan would lead to early detection of such malignancies or serious vascular anomalies post heart transplantation. METHODS This is a single center observational study of patients undergoing surveillance computed tomography of chest, abdomen and pelvis at least 5 years after transplantation. Abnormal findings, included pulmonary nodules, lymphadenopathy and intra-thoracic and intra-abdominal masses and vascular anomalies such as abdominal aortic aneurysm. The clinical follow up of each of these major abnormal findings is summarized. RESULTS A total of 63 patients underwent computed tomography scan of chest, abdomen and pelvis at least 5 years after transplantation. Of these, 54 (86%) were male and 9 (14%) were female. Mean age was 52±9.2 years. Computed tomography revealed 1 lung cancer (squamous cell) only. Non specific pulmonary nodules were seen in 6 patients (9.5%). The most common incidental finding was abdominal aortic aneurysms (N=6 (9.5%)), which necessitated follow up computed tomography (N=5) or surgery (N=1). Mean time to detection of abdominal aortic aneurysms from transplantation was 14.6±4.2 years. Mean age at the time of detection of abdominal aortic aneurysms was 74.5±3.2 years. CONCLUSION Screening computed tomography scan in patients 5 years from transplantation revealed only one malignancy but lead to increased detection of abdominal aortic aneurysms. Thus the utility is low in terms of detection of malignancy. Based on this study we do not recommend routine computed tomography post heart transplantation.