Incidence Of Severe Primary Graft Dysfunction Research Articles

Preoperative Amiodarone and Primary Graft Dysfunction in Heart Transplantation.

Preoperative amiodarone effects on postorthotopic heart transplant (OHT) outcomes remain controversial. The purpose of this study was to determine the effect of cumulative pre-OHT amiodarone exposure on severe primary graft dysfunction (PGD). We retrospectively reviewed adult OHT recipients between August 2012 and June 2018. Primary outcome was severe PGD in patients receiving amiodarone at 3, 6, and 12 months prior to OHT compared with those not receiving amiodarone. Secondary outcomes included intensive care unit (ICU) and hospital length of stay, duration of mechanical ventilation, early graft failure (EGF), mortality at 3, 6, and 12 months post-OHT, and 30-day incidence of postoperative tachyarrhythmias, bradycardia, permanent pacemaker implantation, and rejection. Incidence of severe PGD was 12.5% in those who received amiodarone compared to 6.8% in those who did not (14 vs 6, P = 0.18). Cumulative preoperative amiodarone significantly increased the odds of severe PGD at 3 months (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.001-1.06; P = 0.044) and 6 months (OR: 1.02, 95% CI: 1.003-1.044; P = 0.024) in a multivariate logistic regression. Patients on amiodarone had significantly higher rates of postoperative bradycardia (13.4% vs 4.5%, P = 0.03). A trend toward increased PGD was present in patients receiving preoperative amiodarone. This finding combined with the regression showing significantly increased odds of PGD with increasing 3 and 6 month cumulative amiodarone dose is clinically concerning. Escalation of care with pacemaker implantation was required more frequently in patients on pre-OHT amiodarone.

Increasing Utilization of Extended Criteria Donor Hearts for Transplantation: The OCS Heart EXPAND Trial

BackgroundExtended criteria donor (ECD) hearts available with donation after brain death (DBD) are underutilized for transplantation due to limitations of cold storage. ObjectivesThis study evaluated use of an extracorporeal perfusion system on donor heart utilization and post-transplant outcomes in ECD DBD hearts. MethodsIn this prospective, single-arm, multicenter study, adult heart transplant recipients received ECD hearts using an extracorporeal perfusion system if hearts met study criteria. The primary outcome was a composite of 30-day survival and absence of severe primary graft dysfunction (PGD). Secondary outcomes were donor heart utilization rate, 30-day survival, and incidence of severe PGD. The safety outcome was the mean number of heart graft–related serious adverse events within 30 days. Additional outcomes included survival through 2 years benchmarked to concurrent nonrandomized control subjects. ResultsA total of 173 ECD DBD hearts were perfused; 150 (87%) were successfully transplanted; 23 (13%) did not meet study transplantation criteria. At 30 days, 92% of patients had survived and had no severe PGD. The 30-day survival was 97%, and the incidence of severe PGD was 6.7%. The mean number of heart graft–related serious adverse events within 30 days was 0.17 (95% CI: 0.11-0.23). Patient survival was 93%, 89%, and 86% at 6, 12, and 24 months, respectively, and was comparable with concurrent nonrandomized control subjects. ConclusionsUse of an extracorporeal perfusion system resulted in successfully transplanting 87% of donor hearts with excellent patient survival to 2 years post-transplant and low rates of severe PGD. The ability to safely use ECD DBD hearts could substantially increase the number of heart transplants and expand access to patients in need. (International EXPAND Heart Pivotal Trial [EXPANDHeart]; NCT02323321; Heart EXPAND Continued Access Protocol; NCT03835754)

Impact of pre-lung transplant statin use on the development of primary graft dysfunction.

Primary graft dysfunction (PGD) is a common occurrence following lung transplantation and contributes to short- and long-term morbidity and mortality. Current management strategies are limited, and robust data to support their use is lacking. Preventative strategies attenuating the recipient's inflammatory state suggest statin therapy may decrease the incidence and severity of PGD. This study aims to evaluate the impact of pre-transplant statin use on the incidence and severity of PGD following lung transplantation. A retrospective cohort study was performed evaluating all patients undergoing bilateral lung transplantation from September 2012 to December 2019. The primary outcome was the incidence of PGD by grade, defined as the highest grade of PGD experienced in the first 72h. Secondary outcomes included length of intensive care unit and hospital stays and mortality. Of the 357 patients included in the study, 107 received statin therapy prior to transplant (statin group) and 250 did not (no statin group). PGD occurred in 257 (72%) patients; in the entire cohort, 99 (28%) patients experienced PGD grade 1, 59 (17%) grade 2, and 99 (28%) grade 3. A significantly lower incidence of PGD was observed in the statin group (64.5% vs 75.2%, p= 0.039); however, the association did not remain significant on multinominal analysis for an overall incidence of any PGD (p= 0.275) or incidence of severe PGD (p= 0.240). Statin intensity was not associated with the development of PGD. Pre-transplant statin therapy did not appear to impact the development of PGD following lung transplantation. Future prospective studies should further evaluate the impact of statin intensity and duration on the incidence and severity of PGD.

Outcomes of Mechanical Circulatory Support for Severe Primary Graft Dysfunction After DBD versus DCD Heart Transplantation

<h3>Purpose</h3> Severe primary graft dysfunction (PGD) is defined by need for mechanical circulatory support (MCS) after heart transplantation. Severe PGD is associated with increased short-term mortality but reported outcomes vary widely. The mechanism of PGD may differ for hearts donated after brainstem-determined death (DBD) and circulatory-determined death (DCD). The purpose of this study was to determine whether there are differences in PGD outcomes between DBD and DCD heart transplants. <h3>Methods</h3> We undertook a retrospective, observational study of all heart transplants performed at our institution since the onset of the DCD heart transplant programme (May 2015 to June 2021). Baseline donor and recipient characteristics were recorded. Outcome measures included duration of MCS, length of intensive care (ICU) stay, total length of hospital stay (LOS) and 90-day mortality. <h3>Results</h3> 280 heart transplants were performed during the study period, including 192 DBD and 88 DCD heart transplants. The overall incidence of severe PGD was 11.8% (n=33). These patients were initially supported with VA ECMO (n=28, 84.9%) or CentriMag RVAD (n=5, 15.1%), of which 6 patients (18.2%) were later converted from ECMO to CentriMag RVAD/BiVAD. The incidence of PGD was similar for DBD (n=21, 10.9%) and DCD (n=12, 13.6%) heart transplants (p=0.541). There were no significant differences in baseline characteristics between DBD and DCD groups. There were no significant differences in outcomes between DBD and DCD groups, including median duration (in days) of MCS (5 vs 6, p=0.679), ICU stay (22 vs 20.5, p=0.881) or total LOS (46 vs 48.5, p=0.454). 90-day mortality was 57.1% in the DBD group and 33.3% in the DCD group (p=0.188). <h3>Conclusion</h3> In one of the world's largest cohorts of DCD heart transplantation, we have not seen a significant difference in PGD incidence or outcomes between DBD and DCD heart transplant patients. The potential lower 90-day mortality in the DCD group may suggest that the natural history of PGD after DCD heart transplantation is more favourable compared with PGD seen after DBD heart transplantation.

Lung Transplantation on Cardiopulmonary Bypass: Time Matters

<h3>Purpose</h3> The use of cardiopulmonary bypass (CPB) during lung transplantation (LTx) has been linked to higher rates of primary graft dysfunction (PGD) and worse postoperative outcomes. However, the effect of the duration of CPB has not been examined yet. Thus, the aim of our study was to examine the effect of CPB duration on rates of PGD and survival. <h3>Methods</h3> A retrospective cohort study was performed from a prospective database of adult LTx procedures performed at our institute from 1/2008 to 7/2018 (n = 1039). CPB was utilized in 67% of these procedures. Logistic regression fit model was utilized for univariate analysis of PGD at 72 hours. Nonlinear cumulative logistic mixed model was used in analysis of time related PGD grades and the associated risk factors. The survival rates were evaluated by Kaplan-Meier survival -estimate. <h3>Results</h3> Longer duration of CPB was found to be an independent risk factor for severe PGD (Odds ratio, 1.01 per 1 minute increase in CPB duration; <i>P</i> < 0.001). Patients with higher grades of PGD at 72 hours had a significantly longer duration of CPB (Median, 169, 180, 200, and 233 minutes for PGD0, PGD1, PGD2, and PGD3, respectively; <i>P</i> < 0.001, Figure 1A). The incidence of severe PGD at 0, 24, 48, and 72 hours post-LTx were comparable in patients with no CPB and CPB ≤ 3 hours (16%, 9%, 8%, and 8% vs 26%, 11%, 10%, and 10%, respectively) but these incidences were doubled in patients with CPB > 3 hours (55%, 26%, 25%, and 24%, respectively, Figure 1B). Patients with CPB > 3 hours had the lowest 1-year survival rates compared with CPB ≤ 3 hours and no CPB patients (83%, 89% and 90%, respectively; log-rank <i>P</i> = 0.018). <h3>Conclusion</h3> Analysis of more than 1000 LTx data has shown that longer duration of CPB (>3 hours) is associated with severe PGD and worse survival, while shorter duration of CPB (≤ 3 hours) and no CPB outcomes remain comparable. These results suggest that duration of CPB is more important rather than using CPB itself. Future studies investigating CPB in LTx should consider the duration as an important factor that might affect results.

Incidence, predictors, and outcomes after severe primary graft dysfunction in pediatric heart transplant recipients.

Previous reports of primary graft dysfunction (PGD) in pediatric heart transplant (HT) recipients are limited to descriptive series of children who required extracorporeal membrane oxygenation (ECMO) support shortly after HT. In this study we sought to determine the incidence, risk factors, and survival after severe PGD in pediatric HT recipients. We identified all children <18 years old who underwent HT in the United States during 1996 to 2015 using the Organ Procurement and Transplant Network database and then identified those who developed severe PGD by linking patient variables to Extracorporeal Life Support Organization registry data. Logistic regression models were used to assess risk factors for developing severe PGD. The overall incidence of severe PGD was 4.7% over 20 years (95% confidence interval 4.2% to 5.3%). The incidence was 4.1%, 4.5%, 5.3%, and 4.6%, respectively, in consecutive 5-year periods (p for trend = 0.48). Independent risk factors for developing severe PGD were younger age, congenital heart disease, HT while supported on ECMO, higher serum bilirubin, and graft ischemic time ≥4 hours. Ventricular assist device support as bridge to HT and available donor variables were not associated. Death (or graft loss) before discharge occurred in 40.6% of children with PGD (105 deaths, 7 re-transplants) and in 5.6% of children without PGD. Severe PGD remains an important clinical morbidity in pediatric HT recipients in the current era and is associated with high mortality. These findings highlight the need for research in preventing and treating PGD in pediatric HT recipients for improving overall post-transplant survival.

Does Perfadex Affect Outcomes In Clinical Lung Transplantation?

The use of a low-potassium-based preservation solution improves gas exchange in experimental models of lung transplantation. However, its efficacy in reducing the incidence of primary graft dysfunction (PGD) and improving patient outcomes in the clinical setting is controversial. In this study we measured: oxygenation index (OI); International Society of Heart and Lung Transplantation (ISHLT) PGD grades; extubation times; intensive care unit (ICU) and hospital length of stay; 30-day, 90-day and 1-year survival rates; and bronchiolitis obliterans syndrome (BOS)-free survival. We compared 115 consecutive (2001 to 2004) lung recipients who received allografts preserved with Perfadex, a low-potassium dextran (LPD) solution, and compared the results with the previous 116 consecutive (1999 to 2001) lung recipients who received allografts preserved with modified Euro-Collins (MEC) solution. Recipients were classified as having severe PGD (ISHLT Grade III) if the lowest arterial oxygenation (P) to fraction of inspired oxygen (F) (P/F ratio) within 48 hours post-transplantation was <200. Baseline characteristics of the 2 cohorts were similar except for recipient age (LPD 53.5 vs MEC 49.9 years; p = 0.03). There were no differences in donor age, gender, category of transplant, indication for transplant, use of cardiopulmonary bypass or pre-operative pulmonary artery pressures. When gas-exchange parameters were measured upon arrival to the ICU (T0), at 24 hours post-transplant (T24) and at 48 hours post-transplant (T48), the only significant finding was that the incidence of ISHLT Grade III PGD at T24 was lower in the LPD group compared with the MEC group (8% vs 20%, p = 0.03). The incidence of severe PGD at other timepoints was not statistically different (LPD vs MEC: T0, 17% vs 26%; T0 to T48, 25% vs 31%). Both groups had similar extubation rates at 48 hours post-transplant (LPD 64% vs MEC 67%). The 30-day survival (LPD 93% vs MEC 95%), 90-day survival (LPD 89% vs MEC 89%), 1-year patient survival (LPD 80% vs MEC 77%) and 1-year BOS-free survival (LPD 70% vs MEC 74%) were not statistically different. Lung preservation with LPD as compared with MEC does not improve early gas exchange or impact 90-day and 1-year mortality. Continued investigation into lung preservation solution composition is necessary to reduce the incidence of PGD.

Validation of the proposed ISHLT grading system for primary graft dysfunction following lung transplantation

Introduction: Primary graft dysfunction (PGD) is a frequent early complication of lung transplantation. A grading system has been proposed by the ISHLT for PGD based on arterial oxygenation to fraction of inspired oxygen (P/F) ratios at ICU arrival (T0), 24 hours (T24), and 48 hours (T48) post-transplantation. Our objective was to determine if this PGD grading system is predictive of short-term outcomes. Methods: We reviewed donor and recipient medical records for 369 consecutive lung transplants performed between 1992 and 2003. Grade 0-I recipients had P/F ratios 300, grade II 299–200, and grade III 200. Results: During the study period 237 single (SLT), and 132 bilateral single (BSL) lung transplants were performed. The incidence of severe PGD (grade III) was 25% at T0, 5.4% at T24, and 14% at T48. Grouping recipients by the lowest P/F ratio recorded within 48 (T0-48) hours yielded evenly distributed groups: 130 grade 0-I (35%), 107 grade II (29%), and 132 grade III (35%). Grade III T0-48 recipients had an increased 90 day mortality (18%) versus recipients in grades 0-I (10%) and II (7.5%) (p 0.03). Overall survival (Figure), mean length of ICU and hospital stay also increased in grade III patients (12 and 25 days) versus grades 0-I (4.5 and 15) and II (5.5 and 17 days) (p 0.0001). Conclusions: There is an increased risk of mortality and length of hospital stay associated with grade III PGD. The proposed system can rapidly identify recipients with poor outcomes who may benefit from early aggressive treatment. Refinement of the scoring system may further improve patient risk-stratification.