Significant transmitted coronary artery disease (s-TCAD) is an independent risk factor for cardiovascular death and nonfatal major adverse cardiovascular events (MACE) in patients undergoing a heart transplantation (HT), says a new study. From a cohort of 1,918 cardiac transplant patients, s-TCAD was found in 65 patients (6.9%), classifying it as an independent predictor of cardiovascular mortality (adjusted hazard ratio [HR]: 2.25; 95% confidence interval [CI]: 1.20-4.19; P=0.011). Further analysis reveals s-TACD to be an independent predictor of a combined endpoint cardiovascular death or nonfatal MACE (adjusted HR: 2.42; 95% CI: 1.52-3.85; P < 0.001). “These recipients showed an annualized incidence of cardiovascular death of 2.88%, suggesting that they should be considered and consequently treated as patients with a high cardiovascular risk,” say the paper’s authors, who were led by David Couto-Mallón, MD, from the Hospital Universitario de A Coruña in Spain. “Our results indeed indicate that the cardiovascular risk in patients with s-TCAD is possibly higher than that previously considered in other studies. However, whether this increased risk of adverse cardiovascular outcomes is completely explained by transmitted coronary artery disease (TCAD), or whether it could be related to a higher predisposition to the development of cardiac allograft vasculopathy (CAV) in the long term, is not known.” s-TCAD and all-cause mortality link not significant Further findings from the study, which appears in the Aug. 29 issue of the Journal of the American College of Cardiology, reveal that there was not a statistically significant association between s-TCAD and all-cause mortality (adjusted HR: 1.44; 95% CI: 0.89-2.35; P=0.141). The retrospective multicenter study also reveals that of the 1,918 patients, 937 underwent coronary angiography (c-angio) and TCAD was found in 172 patients (18.3%) and nonsignificant transmitted coronary artery disease (ns-TCAD) in 107 (11.4%). No statistically significant impact of ns-TCAD on clinical outcomes was detected, and the results were similar when reassessed by means of competing-risks regression, added the paper’s authors. The research team concluded that TCAD was not associated with reduced survival in patients alive and well enough to undergo post-HT angiography within the first 3 months. “In our cohort, the prevalence of s-TCADs and nsTCAD increased with the use of male donors, donors of older age, donors who died of cerebrovascular causes, and donors with cardiovascular risk factors,” say the authors of the paper, which was also published Monday online. “The association between age and CAD is already known and confirmed in our study, inasmuch as the frequency of TCAD increased from 2.2% in donors aged <40 years to 8.9% in those aged >40 years. This observation supports the current recommendation of considering pre-transplantation c-angio in donors aged >40 to 45 years or younger if cardiovascular risk factors are present.” Expert commentary Richard Cheng, MD, and Jason Smith, MD, both from the University of California-San Francisco, and Babak Azarbal, MD, from Cedars-Sinai Medical Center in Los Angeles, said the study helped clarify an important controversy: the relevance of donor-transmitted coronary artery disease (DTCAD) in heart transplant patients. In an editorial comment, the experts said it remained unclear whether DTCAD lent itself to increased incidence and, more crucially, accelerated progression of post-transplant CAV and worse clinical outcomes. The commentators went on to outline a number of reasons why the use of donor hearts with CAD was relevant, chief among them, that changes in heart listing criteria in 2018 have led to higher clinical acuity at time of transplant. Also, there was an increasing number of performed heart transplants from donors after circulatory death (DCD) facilitated by the advent of ex vivo perfusion and normothermic regional perfusion. The commentors explained that with DCD hearts, donor angiograms are unlikely to be available, in contrast to donor after brain death (DBD) hearts, for which donor angiograms are either routinely performed or can be readily requested. Highlighting the other major study finding, which showed an association between significant DTCAD and higher cardiovascular death and a composite MACE endpoint, the experts said that consideration should be given to more frequent ischemic evaluation and surveillance coronary angiography in patients who received a donor heart without a donor angiogram and/or of older age. Moreover, whether percutaneous coronary intervention can mitigate the risk of DTCAD remains to be determined. Study methodology The retrospective multicenter study enrolled 1,918 consecutive patients >18 years old who underwent HT in 11 Spanish centers from 2008 to 2018. A baseline c-angio was performed within the first 3 months after HT in 937 (48.9%) of these recipients, who constituted the study population. The median time elapsed from HT to c-angio was 42 days (interquartile range [IQR]: 29-64 days). Pretransplantation angiography in the donor was performed in only four patients (0.4%). As a condition, s-TCAD was defined as any stenosis ≥50% in epicardial coronary arteries, and ns-TCAD as stenosis <50%. Clinical outcomes were assessed via Cox regression and competing risks regression. These patients were followed-up from the date of baseline c-angio until the date of death (median period of 6.3 years). Sources: Couto-Mallón D, Almenar-Bonet L, Barge-Caballero E, et al. Prognostic Relevance of Donor-Transmitted Coronary Artery Disease in Heart Transplant Recipients. J Am Coll Cardiol. 2023;81:753–767. Cheng R, Azarbal B, Smith J. Donor-Transmitted Coronary Artery Disease: Another Avenue to Expand Heart Transplantation? J Am Coll Cardiol. 2023;81:768–770. Image Credit: alisaaa – stock.adobe.com