Incidence, Risk Factors, and Outcomes of Delayed-Onset Cytomegalovirus Disease in a Large, Retrospective Cohort of Heart Transplant Recipients

Background Delayed-onset cytomegalovirus (CMV) disease can occur among heart transplant recipients after stopping anti-CMV prophylaxis. We evaluated a large, retrospective cohort of heart transplant recipients in the United States through the use of billing data from 3 Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases (SID) to determine the epidemiology of delayed-onset CMV disease coded during hospital readmission. Methods We identified 2280 adult heart transplant recipients from 2004 to 2010 through the use of the California, Florida, and New York SID. Demographics, comorbidities, heart failure etiology, CMV disease, and inpatient death were identified. CMV disease was classified as early-onset (≤100 days) or delayed-onset (>100 days after transplant). Possible tissue invasion by CMV was determined through the use of codes for CMV pneumonitis, hepatitis, and gastrointestinal endoscopy. Multivariate analysis was performed with the use of Cox proportional hazards models. Results Delayed-onset CMV disease occurred in 7.5% (170/2280) and early-onset CMV disease occurred in 2.0% (45/2280) of heart transplant recipients. Risk factors for delayed-onset CMV disease included residence in a non-metropolitan locale (aHR. 1.8; 95% confidence interval [CI], 1.0–3.3) and ischemic cardiomyopathy as heart failure etiology (aHR, 1.8; 95% CI, 1.3–2.5). Inpatient death >100 days after transplant was associated with delayed-onset CMV disease with possible tissue invasion (aHR, 2.0; 95% CI, 1.1–3.8), transplant failure or rejection (aHR, 4.0; 95% CI, 2.7–5.8), and renal failure (aHR, 1.5; 95% CI, 1.1–2.0). Conclusions Delayed-onset CMV disease is more common than early-onset CMV disease among heart transplant recipients. These results suggest that delayed-onset tissue-invasive CMV disease may be associated with an increased risk of death.