Editor's Note: Commentary based on Kobashigawa J, Zuckermann A, Macdonald P, et al. Report from a consensus conference on primary graft dysfunction after cardiac transplantation. J Heart Lung Transplant 2014;33:327-40.

Background

At the 33rd annual International Society of Heart and Lung Transplant (ISHLT) meeting, a consensus conference was convened to formulate guidelines regarding primary graft dysfunction (PGD) after heart transplantation. The conference included a summary of survey data collected before the conference, state-of-the-art presentations given at the consensus conference, and consensus statements drawn from group sessions. Each of these areas will be summarized in this review.

Results

An online survey was completed by 47 heart transplant centers internationally comprising almost ten thousand patients with a PGD rate of 7.4%. The 30-day mortality from PGD was 30% and the one-year mortality 34.6%.

Prior studies were highlighted, including the RADIAL score, a validated risk model for the development of PGD. The RADIAL score comprises six factors: four recipient factors including right atrial pressure >10 mm Hg, age >60 years, diabetes, inotropic dependence, and two donor factors including age >30 years and ischemic time >240 minutes. Each risk factor is assigned one point with an incidence of PGD of 12%, 19% and 28% for patients with scores of 0-1, 2, and 3 or more points, respectively.

There are no biomarkers for PGD and treatment is supportive, including inotropic therapy and mechanical circulatory support as either a bridge to recovery or re-transplantation. Several centers, including the Cedars-Sinai Heart Institute, Cleveland Clinic, Columbia University, Johns Hopkins University, and University Heart Centre in Hamburg, Germany offered their specific experience with PGD management. For all centers, management involved first excluding anatomic problems as a cause of graft dysfunction. Escalating doses of inotropic support was initiated and if the hemodynamics were refractory to this, then mechanical support with an intra-aortic balloon pump (IABP) or extracorporeal membrane oxygenation (ECMO) was used. If there was no recovery of function, ECMO was then replaced with short-term paracorporeal mechanical circulatory support (such as the Centrimag) for left-, right-, or biventricular support. If extracardiac organ function remained preserved, the patients were then considered candidates for re-transplantation.

Conclusion

The conference concluded with summary statements on the definition and diagnosis of PGD. PGD was defined as left, right, or biventricular dysfunction in the absence of a discernible cause, including hyperacute rejection, pulmonary hypertension, or a known surgical complication. Mild, moderate, and severe PGD, as well as PGD of the right ventricle only, was defined based on echocardiographic and hemodynamic parameters as outlined in Table 6 in the original article.¹ Other consensus statements included the recommendation that all patients in whom mechanical circulatory support is placed directly into the heart should have a heart biopsy performed at that time and that an autopsy should be performed in all patients who are diagnosed with PGD and subsequently expire.

Commentary/Perspective

This consensus conference provided the first guidelines to better define, diagnose, and manage the care of patients with PGD after heart transplantation. Notably, the conference had 71 participants with vast clinical experience, representing 42 heart transplant centers from North America, Australia, Europe, and Asia. Even more remarkable, the online survey on PGD was completed by 47 heart transplant centers internationally with shared experience on almost ten thousand heart transplant recipients.

In the relatively small world of heart transplantation, randomized controlled trials are rare, and patients are critically ill. Thus, collaboration in the form of consensus conferences is essential to pool judgment and experience in a world where randomized controlled trials are not feasible due to the small sample sizes and acuity of illness. Several important messages have come out of this conference.

First, a strict definition of PGD is essential to create future registries to follow the care and outcomes of patients with PGD. Second, a severity scale ensures that should future studies be undertaken to determine risk factors or effect of therapies, that patients of comparable degree of PGD will be compared. Third, the consensus conference raised awareness of and lent validity to the option of re-transplantation for such patients with PGD, no recovery with supportive care, and preserved extracardiac organ function.

References

1. Kobashigawa J, Zuckermann A, Macdonald P, et al. Report from a consensus conference on primary graft dysfunction after cardiac transplantation. J Heart Lung Transplant 2014;33:327-40.
2. Segovia J, Cosío MD, Barceló JM, et al. RADIAL: a novel primary graft failure risk score in heart transplantation. J Heart Lung Transplant 2011;30:644-51.
3. Cosio Carmena MD, Gómez Bueno M, Almenar L, et al. Primary graft failure after heart transplantation: Characteristics in a contemporary cohort and performance of the RADIAL risk score. J Heart Lung Transplant 2013;32:1187-95.
4. Kittleson MM, Patel JK, Moriguchi JD, et al. Heart transplant recipients supported with extracorporeal membrane oxygenation: outcomes from a single-center experience. J Heart Lung Transplant 2011;30:1250-6.

Keywords: Atrial Pressure, Autopsy, Biomarkers, Biopsy, Cooperative Behavior, Critical Illness, Diabetes Mellitus, Extracorporeal Membrane Oxygenation, Heart Transplantation, Heart Ventricles, Heart-Lung Transplantation, Hypertension, Pulmonary, Lung Transplantation, Primary Graft Dysfunction, Recovery of Function, Registries, Risk, Risk Factors, Tissue Donors, Heart Failure

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