The influence of pulmonary resistance on the success of pediatric heart transplantation: Are there still boundaries?

Elevated pulmonary vascular resistance index (PVRI) has been identified as an important risk factor for early phase mortality in pediatric heart transplantation (1, 2). This is believed to be due to right ventricular dysfunction or failure because the donor heart is not conditioned for the pressure load of elevated PVRI. Current pediatric guidelines suggest that reactivity of the pulmonary vascular bed rather than baseline pulmonary vascular resistance is of importance and that patients who achieve a “best” PVRI of <6 Woods units 9 m (WU 9 m) and/or a transpulmonary gradient of ≤15 mmHg are acceptable pediatric heart transplant candidates (3). Chiu et al. (4) have used the United Network of Organ Sharing database to analyze the impact of elevated PVRI on post-transplant mortality. They found that a PVRI of over 6 WU 9 m was not associated with increased mortality after transplant. They also performed propensity matching of the cohorts to control for other variables, including missing catheterization information, and still found no influence of PVRI on outcomes. These findings are similar to other recent analysis by the Pediatric Heart Transplant Study Group where a PVRI of 5 Woods units 9 m was also not associated with decreased survival in a large, multicenter, pediatric cohort (5). One significant limitation of both of these studies, acknowledged by the authors of this study, is these data are from a selective group of patients who actually were accepted as transplant candidates. Patients who are denied listing because of unacceptable PVRI are not captured in the OPTN or PHTS datasets. There could be a substantial number of variables, including pulmonary vascular vasoreactivity, duration of elevated PVRI, and alternative hemodynamic monitoring, that could lead the clinician to disregard elevated catheterization numbers and continue to list a patient for transplant. This is not captured in the dataset and therefore limits the interpretation of this analysis to determine the true impact of elevated PVRI on a pediatric heart transplant candidate. Another significant limitation that limits the interpretation of this study is accounting for missing data. Only 29% percent of patients in this analysis have usable catheterization data entered into the registry. This could reflect the reluctance of the listing center to catheterize patients who may be too critically ill to tolerate the procedure or missing data inherent in registry analysis. These patients may have un-recognized PVRI elevations that could impact their outcome as well as the conclusion of the study. Additional analysis was performed to account for the amount of missing data, but the lack of standardization of practice including universal pretransplant assessment of PVRI seriously limits the use of registries to answer this question. Despite these limitations, the results of this study challenge, in the current era, the standard dogma about PVRI limitations in determining candidacy for transplantation. Changes in medical practice such as broader use of pulmonary vasodilators and the impact of durable ventricular assist devices to alleviate pulmonary venous congestion driving elevated PVRI provide increased abilities to reverse elevated PVRIs that did not exist prior to the last 10 yr in children. The authors attempted to identify era as a factor for improved survival in patients with elevated PVRI by comparing patients before and after the year 2000. Although there was no effect in this analysis, the question of this influence requires further investigation. Are the old 2007 guidelines really applicable in 2015? The answer is probably not. Are there