Pretransplant Pulmonary Vascular Resistance Research Articles

The Association Between Pre-Transplant PVR and Post-Transplant Outcomes Differs by LVAD Status

<h3>Purpose</h3> Elevated pulmonary vascular resistance (PVR) is a risk factor for mortality after heart transplantation (HT), but whether this association differs for patients with and without LVAD support prior to HT is unknown. <h3>Methods</h3> We analyzed adult first-time HT recipients from the UNOS registry transplanted between 2010 and 2019. As our prior work using the STS-INTERMACS registry established an association between PVR > 1.5 WU and poor outcomes in LVAD recipients, we quantified the independent associations between PVR > 1.5 WU and the outcomes of 30-day graft failure and 1 year mortality using multivariable logistic regression, stratified by LVAD support status at the time of HT. We also examined the association with 10-year survival using multivariable Cox proportional hazards regression. <h3>Results</h3> Among 18913 HT recipients, 9286 (49%) had an LVAD at the time of HT. 6101 (66%) of HT recipients bridged with LVADs had PVR > 1.5 WU at the time of HT, compared with 7114 of 9627 (74%) patients without LVADs. When adjusted for age, waitlist status, creatinine, donor ischemic time, and other important variables, pre-transplant PVR > 1.5 WU was associated with a higher risk of 30-day graft failure (OR 1.28, 95% CI 1.06-1.53, p=0.009, Figure). This risk was limited to patients supported with LVADs at the time of HT (with LVAD OR 1.53, 95% CI 1.21-1.95 vs without LVAD OR 0.96, 95% CI 0.72-1.28, interaction p=0.014). Similar findings were seen for 1 year mortality, though the interaction between LVAD support and PVR was not statistically significant (Figure). PVR > 1.5 WU was not significantly associated with 10-year survival (HR 1.07, 95% CI 1.0-1.15, p=0.053). <h3>Conclusion</h3> The clinical significance of pre-transplant PVR is different for LVAD and non-LVAD bridged HT recipients. HT recipients bridged with LVADs have an increased risk of poor outcomes even with conventionally acceptable PVR values. Whether more aggressive reduction of PVR among HT candidates supported with LVADs can mitigate these risks requires further study.

Abstract 13053: Cardiac Allograft Vasculopathy Following Donation After Circulatory-Determined Death Heart Transplantation

Introduction: Cardiac allograft vasculopathy (CAV) remains a major problem for heart transplant (HTx) recipients, limiting their long-term survival. Our centre has performed the world’s largest series of donation after circulatory-determined death (DCD) HTx. Five-year survival is equivalent to donation after brainstem-determined death (DBD) HTx. However, there is no information on CAV in DCD HTx recipients. We sought to evaluate the incidence of CAV in our cohort of DCD HTx recipients. Methods: All DCD HTx recipients at our centre between February 2015 and December 2019 who had undergone CAV screening were included. They were compared with all DBD recipients during the same period who had undergone CAV screening. Angiograms were retrospectively assigned an ISHLT CAV grade by two independent observers. Results: Thirty-six DCD and 70 DBD HTx recipients were included in the study. Median time to first imaging of coronary arteries was 621 days and 572 days for DCD and DBD cohorts respectively. There was a higher proportion of male donors in the DCD cohort (p= 0.03) but no other significant differences between donor baseline characteristics. DCD recipients had a lower median pre-transplant pulmonary vascular resistance (p=0.03) but there were no other significant differences in recipient baseline characteristics. The two cohorts had similar rates of pre-operative durable LVAD use, post-transplant mechanical circulatory support and post-transplant immunosuppression regimes. There was no significant difference in the rates of CAV between the DBD and DCD groups (p=0.41) (Figure 1). When adjusted for standard risk factors for development of CAV (including donor factors, CMV status and rejection) there remained no significant difference between rates of CAV between groups (OR 1.48, p=0.41, 95% CI 0.58-3.78). Conclusions: DCD HTx recipients have similar rates of CAV when compared to a contemporary population of DBD HTx recipients.

Elevated pre-transplant pulmonary vascular resistance is associated with early post-transplant atrial fibrillation and mortality.

AimsSeverely elevated pre‐transplant pulmonary vascular resistance (PVR) has been linked to adverse effects after heart transplantation (HTX). The impact of a moderately increased PVR before HTX on post‐transplant outcomes remains uncertain. The aim of this study was to investigate the effects of an elevated pre‐transplant PVR ≥ 300 dyn·s·cm−5 (≥3.75 Wood units) on outcomes after HTX.Methods and resultsThis observational retrospective single‐centre study included 561 patients receiving HTX at Heidelberg Heart Center between 1989 and 2015. Patients were stratified by degree of pre‐transplant PVR. Analyses covered demographics, post‐transplant medication, mortality and causes of death after HTX, early post‐transplant atrial fibrillation (AF), and length of the initial hospital stay after HTX. Ninety‐four patients (16.8%) had a PVR ≥ 300 dyn·s·cm−5 (≥3.75 Wood units). These patients had a higher rate of early post‐transplant AF [20.2 vs. 10.7%, difference: 9.5%, 95% confidence interval (CI): 0.9–18.1%, P = 0.01] and an increased 30 day post‐transplant mortality (25.5 vs. 6.4%, hazard ratio: 4.4, 95% CI: 2.6–7.6, P < 0.01), along with a higher percentage of death due to transplant failure (21.2 vs. 4.1%, difference: 17.1%, 95% CI: 8.7–25.5%, P < 0.01). Multivariate analysis revealed a PVR ≥ 300 dyn·s·cm−5 (≥3.75 Wood units) as a significant risk factor for increased 30 day mortality after HTX (hazard ratio: 4.4, 95% CI: 2.5–7.6, P < 0.01). Kaplan–Meier estimator showed a lower 2 year survival after HTX (P < 0.01) in patients with a PVR ≥ 300 dyn·s·cm−5 (≥3.75 Wood units).ConclusionsElevated pre‐transplant PVR ≥ 300 dyn·s·cm−5 (≥3.75 Wood units) is associated with early post‐transplant AF and increased mortality after HTX.

(709) - Outcomes Following Cardiac Transplantation in Children with High Pre-Transplant Pulmonary Vascular Resistance

(709) - Outcomes Following Cardiac Transplantation in Children with High Pre-Transplant Pulmonary Vascular Resistance

Elevated Pre-Transplant Pulmonary Vascular Resistance Is Not Associated with Mortality in Children without Congenital Heart Disease: A Multi-Center Study

Elevated Pre-Transplant Pulmonary Vascular Resistance Is Not Associated with Mortality in Children without Congenital Heart Disease: A Multi-Center Study

Heart Transplantation for Adults With Congenital Heart Disease: Analysis of the United Network for Organ Sharing Database

Congenital heart disease (CHD) in the adult is an uncommon indication for heart transplantation but has been increasing. We assessed survival and predictors of death after heart transplantation for adults with CHD. Adult primary heart transplant recipients (aged > 17 years) reported to the United Network for Organ Sharing (1987 to 2006) were reviewed and categorized by diagnosis of CHD vs other diagnoses. Kaplan-Meier survival analysis and Cox regression modeling were performed. During the study period, 35,334 adults underwent primary heart transplantation, and 689 (2%) had CHD. Adult CHD recipients had longer mean waiting list time (218 vs 195 days; p = 0.004), longer ischemic time (3.5 vs 2.9 hours, p < 0.0001), and were more likely to have pretransplant pulmonary vascular resistance exceeding 4 Woods Units (62% vs 51%, p < 0.0001) vs other recipients. Thirty-day mortality was 16% vs 6% (p < 0.0001), although Kaplan-Meier survival did not differ between groups (p = 0.92) out to 10 years. Ischemic time (hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.02 to 1.35; p = 0.02), African American race (HR, 1.9; 95% CI, 1.04 to 3.58; p = 0.03), and pulmonary vascular resistance exceeding 4 Woods Units (HR, 1.5; 95% CI, 1.01 to 2.19; p = 0.04) were predictors of death for adult CHD recipients. Heart transplantation for adults with CHD is effective and has good long-term prognosis. The 30-day mortality rate is high, but 5- and 10-year survival is not statistically different from patients without CHD.

Evolving practice patterns in heart transplantation: a single-center experience over 15 years

This analysis is a retrospective characterization of evolving patterns in donor and recipient risk factors for early and late outcomes (survival and freedom from rejection) along with determinants of hospital and 1-year mortality after heart transplantation over a 15-year experience in a single center. Profiles and outcomes were evaluated for procedures performed between 1988 and 1995 (group A, n = 105) versus 1996 and 2003 (group B, n = 218). The following parameters were considered: pretransplant diagnosis, recipient age UNOS status, donor age, total postretrieval ischemic time, donor/recipient size match, and degree of myocardial necrosis at biopsy. Recipients in group B were significantly more compromised as demonstrated by UNOS status (11.4% vs 19.3%; P = .05) and pretransplant pulmonary vascular resistance (2.3 ± 1.5 vs 3.1 ± 1.5; P = .04). Marginal donors were more frequently used for group B procedures (21.9% vs 47.7%; P < .0001). Outcomes were significantly more favorable among group B patients in terms of hospital mortality (18.1% vs 10.6%; P = .046), and 1- and 5-year actuarial survival (72.4% vs 83.4%, 60% vs 73.3%, respectively; P = .006). Analysis of the causes of death disclosed a significant reduction in fatal events due to graft failure and acute rejection in group B. No difference emerged with regard to actual freedom from acute rejection. Determinants of hospital mortality were pretransplant diagnosis, UNOS status, donor age, and cardioplegic solution. Transplant era, recipient age, infectious episodes, and ischemic necrosis at biopsy were risk factors for 1-year mortality. We conclude that despite extensive usage of marginal donors and selection of worse candidates, significantly better outcomes were achieved due to improvements in global management strategies.

Impact of current management practices on early and late death in more than 500 consecutive cardiac transplant recipients.

To study risk factors for early and late death after heart transplantation in the current era. The current cardiac transplant population differs from earlier periods in that an increasing number of sicker patients, such as those with ventricular assist device (LVAD) support, prior cardiac allotransplantation, and pulmonary hypertension, are undergoing transplantation. In addition, sensitized patients constitute a greater proportion of the transplanted population. Emphasis has been placed on therapies to prevent early graft loss, such as the use of nitric oxide and improved immunosuppression, in addition to newer therapies. Five hundred thirty-six patients undergoing heart transplantation between 1993 and 1999 at a single center were evaluated (464 adults and 72 children; 109 had received prior LVAD support and 24 underwent retransplantation). The mean patient age at transplantation was 44.9 years. Logistic regression and Cox proportional hazard models were used to evaluate the following risk factors on survival: donor and recipient demographics, ischemic time, LVAD, retransplantation, pretransplant pulmonary vascular resistance, and immunologic variables (ABO, HLA matching, and pretransplant anti-HLA antibodies). The rate of early death (less than 30 days) was 8.5% in adults and 8.8% in children. The actuarial survival rate of the 536 patients was 83%, 77%, and 71% at 1, 3, and 5 years, respectively, by Kaplan Meier analysis. Risk factors adversely affecting survival included the year of transplant, donor age, and donor-recipient gender mismatching. Neither early nor late death was influenced by elevated pulmonary vascular resistance, sensitization, prior LVAD support, or prior cardiac allotransplantation. Previously identified risk factors did not adversely affect short- or long-term survival of heart transplant recipients in the current era. The steady improvement in survival during this period argues that advances in transplantation have offset the increasing acuity of transplant recipients.

Resting hemodynamics after total versus standard orthotopic heart transplantation in patients with high preoperative pulmonary vascular resistance.

Pretransplant pulmonary vascular resistance > or = 4 Wood-units predisposes to right ventricular failure after heart transplantation. Total orthotopic heart transplantation with bicaval and pulmonary venous anastomoses offers synchronous contractions of the atria and a normal ventricular filling pattern, but requires longer ischemic time than standard orthotopic heart transplantation. To test if total orthotopic heart transplantation improves resting hemodynamics in pts with high preoperative pulmonary vascular resistance, we analyzed 65 pts with standard and 65 with total orthotopic heart transplantation transplanted between 12/88 and 7/94. Of these, 18 with total and 15 with standard orthotopic heart transplantation had a preoperative pulmonary vascular resistance > or = 4 Wood-units. Right heart catheterization data were obtained at each endomyocardial biopsy. All data from biopsies at both 2 weeks and 1 year posttransplant that were free from humoral or greater than 1A cellular rejection (9 versus 13 pts) were included in a two way ANOVA. Pts with postop pacemakers, atrial fib or beta-blocker therapy at the time of biopsy were excluded. Ischemic time was different (172 +/- 44 versus 142 +/- 28 min, P = 0.03). Demographics, NYHA class, pre-TX hemodynamics, donor age and inotropes were similar. Cardiac output and index were higher in the total orthotopic group at 2 weeks (6.5 +/- 1.7 versus 5.1 +/- 1.0 l/min; 3.4 +/- 0.9 versus 2.8 +/- 0.6 l/min per m2) and 1 year (7.1 +/- 2.0 versus 4.9 +/- 1.1 l/min, P = 0.002; 3.6 +/- 1.1 versus 2.6 +/- 0.5 l/min per m2, P = 0.009). Right atrial and pulmonary arterial mean pressure (mmHg) were lower with total orthotopic heart transplantation at 2 weeks (6 +/- 4 versus 9 +/- 5, P = 0.04; 22 +/- 3 versus 25 +/- 7, P = 0.1) and 1 year (5 +/- 2 versus 7 +/- 3, P = 0.02; 19 +/- 4 versus 25 +/- 7, P = 0.03). Pulmonary capillary wedge pressure (mmHg) was borderline nonsignificant (11 +/- 4 versus 13 +/- 7 at 2 weeks, 8 +/- 3 versus 14 +/- 5 at 1 year, P = 0.055), as well as pulmonary vascular resistance (1.9 +/- 1 versus 2.5 +/- 1 at 2 weeks, 1.5 +/- 0.6 versus 2.7 +/- 1.7 WU at 1 year, P = 0.051). Total orthotopic heart transplantation improves cardiac output and index in pts with high preoperative pulmonary vacular resistance. There is a lower mean RA and PA pressure perhaps due to less tricuspid and mitral regurgitation. In view of the frequently observed restrictive filling pattern after cardiac transplantation, total orthotopic heart transplantation can be beneficial until this pattern has subsided by preserving atrioventricular synchrony and offering better atrial transport.

Improved resting hemodynamics after total vs standard orthotopic heart transplantation in patients with high preoperative pulmonary vascular resistance

Objective: Pretransplant pulmonary vascular resistance ] 4 Wood-units predisposes to right ventricular failure after heart transplantation. Total orthotopic heart transplantation with bicaval and pulmonary venous anastomoses offers synchronous contractions of the atria and a normal ventricular filling pattern, but requires longer ischemic time than standard orthotopic heart transplantation. To test if total orthotopic heart transplantation improves resting hemodynamics in pts with high preoperative pulmonary vascular resistance, we analyzed 65 pts with standard and 65 with total orthotopic heart transplantation transplanted between 12:88 and 7:94. Of these, 18 with total and 15 with standard orthotopic heart transplantation had a preoperative pulmonary vascular resistance ]4 Wood-units. Methods: Right heart catheterization data were obtained at each endomyocardial biopsy. All data from biopsies at both 2 weeks and 1 year posttransplant that were free from humoral or greater than 1A cellular rejection (9 versus 13 pts) were included in a two way ANOVA. Pts with postop pacemakers, atrial fib or b-blocker therapy at the time of biopsy were excluded. Results: Ischemic time was different (1729 44 versus 1429 28 min, P 0.03). Demographics, NYHA class, pre-TX hemodynamics, donor age and inotropes were similar. Cardiac output and index were higher in the total orthotopic group at 2 weeks (6.591.7 versus 5.191.0 l:min; 3.49 0.9 versus 2.89 0.6 l:min per m 2 ) and 1 year (7.19 2.0 versus 4.99 1.1 l:min, P0.002; 3.691.1 versus 2.690.5 l:min per m 2 , P 0.009). Right atrial and pulmonary arterial mean pressure (mmHg) were lower with total orthotopic heart transplantation at 2 weeks (69 4 versus 99 5, P 0.04; 229 3 versus 2597, P0.1) and 1 year (592 versus 793, P0.02; 1994 versus 259 7, P 0.03). Pulmonary capillary wedge pressure (mmHg) was borderline nonsignificant (1194 versus 1397 at 2 weeks, 89 3 versus 149 5 at 1 year, P 0.055), as well as pulmonary vascular resistance (1.991 versus 2.591 at 2 weeks, 1.59 0.6 versus 2.79 1.7 WU at 1 year, P 0.051). Conclusions: Total orthotopic heart transplantation improves cardiac output and index in pts with high preoperative pulmonary vacular resistance. There is a lower mean RA and PA pressure perhaps due to less tricuspid and mitral regurgitation. In view of the frequently observed restrictive filling pattern after cardiac transplantation, total orthotopic heart transplantation can be beneficial until this pattern has subsided by preserving atrioventricular synchrony and offering better atrial transport. © 1997 Elsevier Science B.V.