When Bad Things Happen to Good Hearts: Prediction and Management of Primary Graft Dysfunction

Primary graft dysfunction (PGD) occurs in nearly 8%-10% of heart transplant recipients, and is the most consequential early complication with an associated reduction in 1-year survival from 95% to 75%. The biological mechanisms underpinning PGD are the subject of ongoing investigations, and thus recognizing, preventing, and treating PGD remain elusive goals. The present expert review summarizes salient developments in the prediction and management of PGD. The International Society for Heart & Lung Transplantation (ISHLT) consensus definition and its severity was developed more than a decade ago. Since then, a significant volume of literature has attempted to elucidate risk factors for PGD at the donor, recipient, and procedural level. Importantly, updated international consensus guidelines, currently in press, have revisited and modernized the definitions and grading of PGD to reflect contemporary practice. Although previously validated prediction tools have performed poorly in contemporary data sets, more updated and clinically relevant models have been developed by leveraging multinational data and machine learning algorithms. Translational research has identified several donor and recipient biomarkers that promise to revolutionize current prediction paradigms. With respect to the prevention of PGD, novel preservation systems have yielded encouraging early data for expanding the potential donor pool while reducing risk of PGD, but vigorous assessment through randomized trials is still lacking. Finally, although the mainstay of PGD management remains the use of vasoactive medications and mechanical circulatory support, there have been recent publications on pharmacological and nonpharmacological treatments for PGD that might reduce the clinical effects of this deadly complication. Although there remains a significant need to reduce the burden of PGD after heart transplantation, evolving literature suggests that with enough validated data, PGD might be a predictable phenomenon, the burden of which can be mitigated by targeted interventions at discrete time points. Performance of multicentre, prospective, and when possible randomized trials will be crucial to ensuring that future clinical practice is guided by robust evidence.