Primary isolated right ventricular failure after heart transplantation: prevalence, right ventricular characteristics, and outcomes.

To determine the prevalence, right ventricular (RV) characteristics, and outcomes of primary isolated RV failure (PI-RVF) after heart transplant (HTX). PI-RVF was defined as (1) the need for mechanical circulatory support post-transplant, or (2) evidence of RVF post-transplant as measured by right atrial pressure (RAP) > 15 mmHg, cardiac index of < 2.0 L/min/m2 or inotrope support for < 72 h, pulmonary capillary wedge pressure < 18 mmHg, and transpulmonary gradient < 15 mmHg with pulmonary systolic pressure < 50 mmHg. PI-RVF can be diagnosed from the first 24-72 h after completion of heart transplantation. A total of 122 consecutive patients who underwent HTX were reviewed. Of these, 11 were excluded because of secondary causes of graft dysfunction (GD). PI-RVF was present in 65 of 111 patients (59%) and 31 (48%) met the criteria for PGD-RV. Severity of patients with PI-RVF included 41(37%) mild, 14 (13%) moderate, and 10 (9%) severe. The median onset of PI-RVF was 14 (0-49) h and RV recovery occurred 5 (3-14) days after HTX. Severe RV failure was a predictor of 30-day mortality (HR 13.2, 95% CI 1.6-124.5%, p < 0.001) and post-transplant dialysis (HR 6.9, 95% CI 2.0-257.4%, p = 0.001). Patients with moderate PI-RVF had a higher rate of 30-day mortality (14% vs. 0%, p = 0.014) and post-operative dialysis (21% vs. 2%, p = 0.016) than those with mild PI-RVF. Among patients with mild and moderate PI-RVF, patients who did not meet the criteria of PGD-RV had worsening BUN/creatinine than those who met the PGD-RV criteria (p < 0.05 for all). PI-RVF was common and can occur after 24 h post-HTX. The median RV recovery time was 5 (2-14) days after HTX. Severe PI-RVF was associated with increased rates of 30-day mortality and post-operative dialysis. Moderate PI-RVF was also associated with post-operative dialysis. A revised definition of PGD-RV may be needed since patients who had adverse outcomes did not meet the criteria of PGD-RV.

Circulating growth differentiation factor-15 as a novel biomarker in heart transplant.

AIMS: This study aimed to examine (i) whether circulating growth differentiation factor-15 (GDF-15) is associated with acute cellular cardiac allograft rejection (ACR); (ii) a longitudinal trend of GDF-15 after heart transplantation; and (iii) the prognostic value of GDF-15 in predicting a composite outcome of severe primary graft dysfunction (PGD) and 30 day mortality post-transplant. METHODS AND RESULTS: Serum samples were collected before heart transplantation and at every endomyocardial biopsy (EMB) post-heart transplantation in de novo transplant patients. A total of 60 post-transplant serum samples were matched to the corresponding EMBs. Seven (12%) were considered International Society for Heart Lung Transplantation Grade 1R ACR, and one (2%) was identified as Grade 2R ACR. GDF-15 levels in patients with ACR were not different from those in the non-rejection group (6230 vs. 6125 pg/mL, P = 0.27). GDF-15 concentration gradually decreased from 8757 pg/mL pre-transplant to 5203 pg/mL at 4 weeks post-transplant. The composite adverse outcome of PGD and 30 day mortality was significantly associated with increased post-operative GDF-15 (odds ratio: 40; 95% confidence interval: 2.01-794.27; P = 0.005) and high inotrope score post-transplant (odds ratio: 18; 95% confidence interval: 1.22-250.35; P = 0.01). CONCLUSIONS: Circulating GDF-15 concentration was markedly elevated in patients with end-stage heart failure and decreased after heart transplantation. GDF-15 was significantly associated with post-transplant PGD and mortality. A lack of association between ACR and GDF-15 did not support routine use of GDF-15 as a biomarker to detect ACR. However, GDF-15 may be potentially useful to determine heart transplant recipients at high risk for adverse post-transplant outcomes. We suggest that GDF-15 levels in recipient serum can provide risk stratification for severe PGD including death during post-operative period. This novel biomarker may serve to inform and guide timely interventions against severe PGD and adverse outcomes during the first 4 weeks after transplantation. Further studies to support the utility of GDF-15 in heart transplantation are required.

Low-dose basiliximab induction therapy in heart transplantation.

We prospectively studied efficacy and safety outcomes of two 10-mg doses of intravenous basiliximab on day 0 and day 4 for induction therapy in 17 consecutive de novo heart transplant recipients. By the 2-week assessment post-transplant, there were no deaths, graft failures, or acute cellular rejections (ACRs) ISHLT grade ≥ 2R. By the 1-year assessment post-transplant, there were 1 (6%) infectious death, no graft failures, 2 (12%) grade 2R ACRs, 6 (35%) asymptomatic cytomegalovirus (CMV) infections, and 4 (25%) treated infections. Our study was the first to show that low-dose basiliximab induction in heart transplant resulted in favorable efficacy and safety outcomes. Additionally, calcineurin inhibitor (CNI) initiation in a low-risk population could be safely delayed using the strategy of modified low-dose postoperative basiliximab. This strategy also appears to allow subsequent early corticosteroid wean, although with the concomitant maintenance of higher CNI levels and higher dosing of mycophenolate.