Chicken or Egg: Tricuspid Regurgitation—The Cause or the Consequence of Post–Heart Transplant Allograft Dysfunction

Tricuspid regurgitation (TR) is the most common valvular abnormality in cardiac transplant recipients.1 The causes of posttransplant TR are often obscure and can be multifactorial.2,3 The prognostic significance of posttransplant TR and the clinical implications of the severity of TR remain unclear and undefined.4-6 To clarify these questions, Bart et al7 conducted a retrospective study of their heart transplant patients over a 6-y period, examining transthoracic echocardiograms in 163 patients. Of these patients, 142 had a transthoracic echocardiograms before their first posttransplant endomyocardial biopsy (EMB). At month 0 posttransplant, 127 patients (78%) had no or mild TR before their first EMB, whereas 36 patients (22%) had moderate–severe TR.7 In patients with no or mild TR, 9 (7%) progressed to moderate–severe TR by 6 mo and 1 underwent tricuspid valve (TV) surgery.7 Of the patients with moderate–severe TR before the first biopsy, by 2 y, 3 had undergone TV surgery. Furthermore, in the moderate–severe TR before first biopsy group, postoperative extracorporeal membrane oxygenation (ECMO) use was significantly more common (78%; P < 0.05), as was rejection frequency (P = 0.02).7 Patients with late progressive moderate–severe TR had a significantly higher 2-y mortality than those who had moderate–severe TR immediately.7 Severe TR post–heart transplant is associated with a worse outcome8 although the clinical outcomes are otherwise variable.4 The consequences of severe TR can result in right ventricular dilatation with hepatic and renal congestion and subsequent dysfunction. Major causes of posttransplant TR include damage to the TV from the EMB and perioperative complications such as primary graft dysfunction (PGD), which often requires ECMO. This would explain the association of ECMO with moderate–severe TR. Additionally, rejection frequency was associated with greater severity of TR. This may be because of injury to the allograft from rejection as well as performing more EMB to make the diagnosis of rejection with concomitant damage to the TV. There has been some evidence that bicaval heart transplants are less likely to develop severe TR as opposed to the older biatrial transplant technique.9,10 However, the current study did not observe a difference. This retrospective study has significant limitations, which are clearly delineated by the authors. A retrospective, single-center study is likely not able to determine if there are specific factors that have causality in the development of TR, its severity, and its progression. The predominant use of the biatrial approach among this study’s patients would limit the ability to distinguish one surgical approach from another in terms of causality of TR. The increasing use of the bicaval approach may reduce the likelihood of developing TR or severe TR. The correlation of ECMO with the development of moderate–severe TR and worse prognoses would suggest that the presence of moderate–severe TR would be a consequence of severe allograft dysfunction posttransplant, necessitating resorting to ECMO for postoperative support. These patients would have worse prognoses on the basis of having PGD, and the severity of TR would, in essence, be an epiphenomenon and a surrogate marker of severe allograft dysfunction posttransplant, given the increased likelihood of developing hepatic and renal congestion and subsequent end-organ dysfunction with severe TR. We can conclude from the results of the current study that TR severity and progression are unsurprisingly associated with severe posttransplant allograft dysfunction with damage to the valve and allograft function. This and the concomitant TV valve damage would adversely affect posttransplant outcomes. The association of rejection frequency with TV severity could be associated with EMB-induced TR, which is also not surprising. What is missing from this study is a more prospective assessment of the relationship of pretransplant and posttransplant pulmonary hemodynamics and volume status to the development of and the severity of TR as well as the relationship with risk factors of PGD. This article serves as a starting point for future investigations. Ultimately, to resolve the questions raised by this article and to better understand the causes and risk factors of TR and prognostic factors of TR development and severity, a larger, prospective, multicenter study collecting echocardiographic information of TR severity, relationship of TR with type of transplant surgery performed, correlation of pulmonary hemodynamics with severity of TR, and prognosis and correlation of number of biopsies and rejection episodes with severity of TR should be performed. The care of transplant patients has changed with greater reliance on noninvasive biomarkers to assess the need for performing EMB, thus reducing the numbers of EMB. This may reduce the incidence and severity of TR. Given the large number of heart transplant programs in the United States that have switched to a biomarker-guided posttransplant strategy (donor-derived cell-free DNA, gene expression profiling) with biopsy minimization, it may be difficult to compare this approach with the more traditional biopsy-guided approach in terms of the impact on TR.