J. Goekler

Diminished impact of cytomegalovirus infection on graft vasculopathy development in the antiviral prophylaxis era - a retrospective study

Evidence concerning an association between cytomegalovirus (CMV) infection and accelerated cardiac allograft vasculopathy (CAV) is inconclusive. Data were analyzed retrospectively from 297 consecutive heart transplants between 1.1.2002 and 31.12.2012. Patients ≤18 years of age, survival, and follow‐up ≤1‐year post‐transplant and patients with early CAV were excluded. CMV‐infection was diagnosed and monitored closely in the first year. CAV was diagnosed by coronary angiography via left heart catheterization, and results were categorized according to the International Society of Heart and Lung Transplantation (ISHLT) scoring system. Risk factors for CAV were tested in a multivariable model. Median follow‐up was 7.5 years (IQR: 5.6–10.3). CMV infection in the first year after transplantation occurred in 26% of patients (n = 78), CMV disease in 5% (n = 15). CAV ≥1 ISHLT was detected in 36% (n = 108). Incidence of CAV >1 ISHLT and severity of CAV increased over time. No statistically significant association between CMV infection and disease within the first year and risk of CAV after 1‐year post‐HTx was detected in the univariate (P = 0.16) and multivariable [hazard ratio (HR), 1.36; confidence interval (CI), 0.89–2.07; P = 0.16] Cox regression. In the multivariable Cox regression, donor age (HR, 1.04; 95% CI, 1.02–1.06; P < 0.01) and acute cellular rejection (ACR) ≥2R in the first year after HTx (HR, 1.77; 95% CI, 1.06–2.95; P = 0.03) were independent risk factors for CAV development. In our cohort, CMV infection and disease in the first year after transplantation did not significantly influence the risk of CAV in the long‐term follow‐up.

Exploring the cardiac response to injury in heart transplant biopsies

BACKGROUND Because injury is universal in organ transplantation, heart transplant endomyocardial biopsies present an opportunity to explore response to injury in heart parenchyma. Histology has limited ability to assess injury, potentially confusing it with rejection, whereas molecular changes have potential to distinguish injury from rejection. Building on previous studies of transcripts associated with T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR), we explored transcripts reflecting injury. METHODS Microarray data from 889 prospectively collected endomyocardial biopsies from 454 transplant recipients at 14 centers were subjected to unsupervised principal component analysis and archetypal analysis to detect variation not explained by rejection. The resulting principal component and archetype scores were then examined for their transcript, transcript set, and pathway associations and compared to the histology diagnoses and left ventricular function. RESULTS Rejection was reflected by principal components PC1 and PC2, and by archetype scores S2TCMR, and S3ABMR, with S1normal indicating normalness. PC3 and a new archetype score, S4injury, identified unexplained variation correlating with expression of transcripts inducible in injury models, many expressed in macrophages and associated with inflammation in pathway analysis. S4injury scores were high in recent transplants, reflecting donation-implantation injury, and both S4injury and S2TCMR were associated with reduced left ventricular ejection fraction. CONCLUSION Assessment of injury is necessary for accurate estimates of rejection and for understanding heart transplant phenotypes. Biopsies with molecular injury but no molecular rejection were often misdiagnosed rejection by histology.TRAIL REGISTRATION. ClinicalTrials.gov NCT02670408FUNDING. Roche Organ Transplant Research Foundation, the University of Alberta Hospital Foundation, and Alberta Health Services.

Cardiac Surgery After Heart Transplantation: Elective Operation or Last Exit Strategy?

Background Because of improved long-term survival after heart transplantation (HTx), late graft pathologies such as valvular disease or cardiac allograft vasculopathy (CAV) might need surgical intervention to enhance longer survival and ensure quality of life. To this date, there exist no guidelines for indication of cardiac surgery other than retransplantation after HTx. Methods In this retrospective, single-center study, we evaluated patients who underwent cardiac surgery after HTx at our institution. Results Between March 1984 and October 2016, 17 (1.16%) of 1466 HTx patients underwent cardiac surgery other than retransplantation after HTx. Indication were valvular disease (n = 7), CAV (n = 6), and other (n = 4). Of these, 29.4% (n = 5) were emergency procedures and 70.6% were elective cases. Median age at time of surgery was 61 years (interquartile range, 52-66 years); 82.4% (n = 14) were male. Median time to surgery after HTx was 9.3 years (2.7-11.1 years). In-hospital, mortality was 11.8% (n = 2); later need of retransplantation was 11.8% (n = 2) due to progressing CAV 3 to 9 months after surgery. One-year survival was 82.35%; overall survival was 47.1% (n = 8) with a median follow-up of 1477 days (416-2135 days). Overall survival after emergency procedures was 209 days (36-1119.5 days) whereas, for elective procedures, it was 1583.5 days (901.5-4319 days). Conclusions Incidence of cardiac surgery after HTx in our cohort was low (1.16%) compared with that of other studies. In elective cases, long-term survival was good.