Post-heart Transplant Mortality Research Articles

Association between pre-heart transplant kidney function and post-transplant outcomes in Black and White adults.

It remains unknown whether estimated glomerular filtration rate (eGFR) using the refit Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation without a term for race is associated with mortality and the need for kidney replacement therapy (KRT) differentially between Black and White heart transplant recipients. We studied 25,900 adults included in the Scientific Registry of Transplant Recipients. We classified recipients into six categories of eGFR (< 30, 30 to < 45, 45 to < 60, 60 to < 90, 90 to < 120, ≥ 120ml/min/1.73 m2) using the race-neutral CKD-EPI refit equation, and assessed survival with multivariable adjusted Cox proportional hazards regression. The association between pre-transplant race-neutral eGFR and mortality varied by race (Pinteraction = 0.006). Compared to White patients with an eGFR of 90-120ml/min/1.73 m2, the mortality rates were 57% (95% CI 1.25, 1.98), 29% (95% CI 1.11, 1.51), 34% (95% CI 1.19, 1.52), and 19% (95% CI 1.06, 1.33) higher in Black patients with an eGFR less than 30, 30-45, 45-60, and 60-90ml/min/1.73m2, respectively; and 53% (95% CI 1.28, 1.82), 49% (95% CI 1.33, 1.66), and 23% (95% CI 1.11, 1.35) higher among White patients with an eGFR less than 30, 30-45, and 45-60ml/min/1.73 m2, respectively. The association between pre-transplant eGFR and the need for KRT during follow-up was similar between Black and White patients (Pinteraction = 0.57). Worsening pre-transplant eGFR using the new race-neutral CKD-EPI refit equation was associated with a higher rate of post-heart transplant mortality and KRT in Black and White recipients. The racial disparity in post-heart transplant mortality was narrower in the setting of severe kidney dysfunction.

The Impact of Pre-Heart Transplantation Blood Transfusion Varies Based on Recipient MELD-XI Score.

Prior studies reveal adverse effects of transfusion on cardiac surgery, but little is known of transfusion impact on heart transplantation. First-time, single-organ adult heart transplant recipients between January 1, 2010, and December 31, 2020, were included, stratified above or below a model for end-stage liver disease excluding international normalized ratio (MELD-XI) score of 9.4, and propensity score matched to their nearest neighbor. A 90 day landmark analysis within each cohort was also performed. Unadjusted analysis showed transfusion recipients, MELD-XI ≥9.4, were more likely to experience post-heart transplantation mortality (Hazard Ratio (HR), 1.352 [95% Confidence Interval (CI), 1.239-1.477], p < 0.001), persisting after adjustment for potential confounders (adjusted HR, 1.211 [95% CI, 1.100-1.335], p < 0.001) and after propensity-score matching (HR, 1.174 [95% CI, 1.045-1.319], p = 0.007). Post-transplant length of stay was longer (25.9 vs. 23.2 days, p < 0.001). Post-transplant dialysis was more common (18.7 vs. 15.9%, p = 0.009). There was no survival difference on 90 day landmarked analysis ( p = 0.108). With MELD-XI <9.4, there was slight survival detriment among transfusion recipients on univariable analysis (HR, 1.111 [95% CI, 1.001-1.234], p = 0.049) but not on multivariable analysis (adjusted HR, 1.061 [95% CI, 0.952-1.181], p = 0.285). There was similar survival after propensity-score matching (HR, 1.032 [95% CI, 0.903-1.180], p = 0.642) and on landmark analysis ( p = 0.581). Ultimately, transfusion was associated with worse post-heart transplantation outcomes among recipients with a MELD-XI ≥9.4.

Risk Factors for 1-Year Mortality After Heart Transplant in Obese Patients Bridged With an LVAD

BackgroundHeart transplantation is relatively contraindicated in morbidly obese patients because of increased morbidity and mortality. This study identified risk factors for post–heart transplantation mortality in obese patients with a left ventricular assist device (LVAD). MethodsThe United Network for Organ Sharing database was used to identify patients with a body mass index ≥35 kg/m2 who had a durable LVAD at the time of isolated heart transplantation between 2010 and 2021. The primary outcome was post–heart transplantation 1-year mortality. Multivariable Cox regression modeling was used to identify significant risk factors for 1-year mortality. Receiver-operating characteristic analyses were performed to identify optimal thresholds for continuous variables associated with the primary outcome. Patients were stratified by the number of risk factors, and Kaplan-Meier analysis was used to compare survival. ResultsA total of 1222 obese patients were bridged to heart transplantation with a durable LVAD. Six risk factors were identified as significantly associated with 1-year post–heart transplantation mortality: recipient age >62.5 years, body mass index >36.6 kg/m2, bilirubin level >0.95 mg/dL, cold ischemic time >3.7 hours, recipient-donor sex mismatch, and pretransplantation mechanical ventilation. The distribution of cumulative risk factors was as follows: 8.6% with 0, 30.6% with 1, 37.0% with 2, and 23.8% patients with ≥3 risk factors. The 1-year survival rate decreased significantly from 96.0% in those patients with 0 risk factors to 77.6% in those with 3 or more risk factors. ConclusionsThese data provide a useful guide for risk stratification and patient selection in obese LVAD candidates being considered for heart transplantation.

The impact of obesity and LVAD-bridging on heart transplant candidate outcomes: a linked STS INTERMACS – OPTN/UNOS data analysis

Limited data integrating waitlist and postheart transplant (HT) mortality have evaluated outcomes of left ventricular assist device (LVAD)-bridged strategy vs no LVAD according to patient characteristics. We evaluated waitlist and post-HT mortality in LVAD-bridged vs nonbridged patients based on body mass index (BMI). We included linked adults listed for HT in Organ Procurement and Transplant Network/United Network for Organ Sharing and patients receiving durable LVAD as bridge to HT or candidacy in Society of Thoracic Surgeons/Interagency Mechanical Circulatory Support databases (2010-2019). Using BMI at listing or LVAD implant, we categorized patients as underweight (<18.5kg/m2), normal weight (18.5-24.99kg/m2), overweight (25-29.99kg/m2), and obese (≥30kg/m2). Kaplan-Meier analysis and multivariable Cox proportional hazards models informed the effect of LVAD-bridged and nonbridged strategy by BMI on waitlist, post-HT, and overall mortality (including waitlist and post-HT mortality). Among 11,216 LVAD-bridged and 17,122 nonbridged candidates, bridged candidates were more frequently obese (37.3% vs 28.6%) (p<0.001). Multivariable analysis indicated increased waitlist mortality in LVAD-bridged vs nonbridged with overweight (Hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.02-1.36) or obesity (HR 1.35, 95%CI 1.17-1.56) in comparison to normal weight candidates (HR 1.02, 95%CI 0.88-1.19) (p-interaction < 0.001). Post-transplant mortality was not statistically different in LVAD-bridged vs nonbridged patients across BMI categories (p-interaction = 0.26). There was a nonsignificant graded increase in overall mortality in LVAD-bridged with overweight (HR 1.53, 95%CI 1.39-1.68) or obesity (HR 1.61, 95%CI 1.46-1.78) compared to nonbridged patients (p-interaction = 0.13). LVAD-bridged candidates with obesity had higher waitlist mortality compared to nonbridged candidates with obesity. Post-transplant mortality was similar in LVAD-bridged and nonbridged patients, but obesity remained associated with increased mortality in both groups. This study may aid clinicians and advanced heart failure patients with obesity in decision-making.

Hypotensive Response On Cardiopulmonary Stress Test Is Not Associated With Worse Post-heart Transplant Clinical Outcomes And Mortality

Hypotensive Response On Cardiopulmonary Stress Test Is Not Associated With Worse Post-heart Transplant Clinical Outcomes And Mortality

Paralytics and Total Parenteral Nutrition Predict Post-Heart Transplant Mortality in Infants

<h3>Purpose</h3> Many have discussed the perils of "limping to transplant" & have identified risk factors associated with poor heart transplant (HTx) survival. We sought to determine the effect of total parenteral nutrition (TPN)-dependence & paralytics on HTx survival. <h3>Methods</h3> UNOS & PHIS data were used to identify infants listed for HTx (1996-2020) on mechanical ventilation (MV; ≥2 consecutive days pre-HTx), paralytics (insurance-charge on ≥3/5 days pre-HTx), &/or TPN-dependent (insurance-charge for TPN on ≥3/5 days pre-HTx; no charges for oral nutrition on 5/5 days). <h3>Results</h3> 1,425 patients were identified: MV (n=355), paralytics (n=132), and/or TPN (n=351). DCM was more common in those on MV & paralytics, whereas TPN patients had more organ dysfunction & ECMO (p<0.01 for all; Table). 1-year mortality was independently predicted by MV (HR 1.5 (95% CI 1.1-2.0), p=0.01), paralytics (1.8 (1.2-2.8), p<0.01), & TPN (1.6 (1.2-2.2), p<0.01). Requirement for all three was the greatest predictor of mortality (2.3 (1.2-4.4), p<0.01), whereas requirement of none was protective (0.6 (1.2-2.2), p<0.01). As mutually exclusive groups, MV did not independently predict mortality compared to no-support (1.4 (0.9-2.3), p=0.14) or all others (0.7 (0.7-1.7), p=0.69) but all other combinations of TPN, MV, & paralytics were predictive of mortality (p≤0.03 for all; Figure). <h3>Conclusion</h3> Paralytics &/or TPN at transplant independently predicted mortality in infants following HTx. Surprisingly, MV alone was not predictive, although over half of patients on MV were also on paralytics or TPN. This study demonstrates the complexity of what it means to "limp to transplant."

Mechanical support for the failing single ventricle after Fontan

Mechanical support for the failing single ventricle after Fontan

Association between continuous-flow left ventricular assist device infections requiring long-term antibiotic use and post-heart transplant morbidity and mortality.

There exists controversy regarding the impact of infection in patients with a left ventricular assist device (LVAD) on post-heart transplant outcomes. This study evaluated the association between infections during LVAD support and the risk of early and late post-heart transplant infection, rejection, and mortality in transplant recipients bridged with an LVAD. This is a single-center retrospective observational cohort study of consecutive adults supported with a continuous flow LVAD undergoing heart transplant between 2006 and 2019 at the Toronto General Hospital. The grade of LVAD infection was classified as per International Society of Heart and Lung Transplantation guidelines. Patients were divided into three groups: (1) patients with LVAD-specific infection confirmed with positive cultures requiring long-term antibiotic use until the time of transplant; (2) patients with any type of infection in whom antibiotics were stopped at least 1 month before transplant; (3) patients without any infections between LVAD implant and transplant. Logistic regression and Cox proportional hazard models were used to evaluate early- and late-post transplant outcomes, respectively. We included 75 LVAD recipients: 16 (21%) patients had a chronic LVAD-related infection on suppressive antibiotics, 30 (40%) had a resolved infection, and 29 (39%) had no infections. During a median post-transplant follow-up time of 4 (2 to 7) years, 65 (87%) patients developed infections, 43 (64%) rejections, and 17 (23%) deaths. Both short- and long-term risks of infection, rejection, and mortality did not differ significantly among the groups. LVAD patients with infections did not have a significantly higher risk of infection, rejection, or mortality at any time point after transplant.

Post-Heart Transplant Outcomes by Recipient Working Status

<h3>Purpose</h3> Pre-transplant employment status has been shown to be a good prognosticator of post-transplant outcomes in certain organ transplant populations. We sought to evaluate the effect of working status on heart transplant (HT) recipients at the time of transplant on long-term survival. <h3>Methods</h3> We performed a retrospective analysis of 31,597 first time HT recipients from the UNOS registry from 2004-2020. Comparisons between patient characteristics of HT recipients working at time of transplant (N=2696) and those not working (N=28,901) were made using standard statistical methods. Cox proportional hazards regression model was applied to adjust for covariates that could confound post-transplant survival analysis. <h3>Results</h3> HT recipients who were working at time of transplant were more likely to be younger (52.0 ± 11.8 vs 53.5 ± 12.5, p <0.001) and male (77.1% vs 74.2%, p <0.001). This group had fewer comorbidities, with lower rates of diabetes (21.6% vs 27.7%, p<0.001), prior non-transplant cardiac surgery (34.9% vs 38.2%, p<0.001), dialysis requirement (1.1% vs 1.9%, p=0.004), and smoking (39% vs 47.9%, p<0.001). The working HT recipients had lower rate of life support use at time of transplant, particularly with IABP use (10.5% vs 8.6%, p=0.001). There was no difference in the median time on the wait list, and working recipients were less likely to be in a higher status listing. There was lower overall post-heart transplant mortality in the working recipients compared to the non-working recipients in the 150 months follow-up period (p<0.001). Working at time of transplant was associated with decreased mortality (HR=0.78, 95% CI 0.71 to 0.86). <h3>Conclusion</h3> HT recipients who were working at the time of their transplant tended to be younger with fewer co-morbidities. These patients' peri-operative acuity also tended to be lower. Working HT recipients had better long-term survival compared to non-working HT recipients. These findings suggest that more consideration should be given to work status as part of heart transplant candidacy evaluation.

Ischemic Time Greater Than Four Hours is Associated with Increased Mortality among Candidates Listed and Transplanted under the New Donor Heart Allocation System

<h3>Purpose</h3> Wider regional sharing of donor hearts under the new allocation system has led to significantly longer ischemic times (IT). Prior reports suggest longer IT increase the risk of post-heart transplantation (HTx) mortality. We sought to determine the effect of IT on HTx survival under the new allocation system. <h3>Methods</h3> The United Network for Organ Sharing (UNOS) database was queried for all candidates listed and transplanted from October 2018 to March 2020. Recipients were stratified into quartiles based on organ IT. Univariate analysis was performed using the Kaplan-Meier method. The adjusted association between IT and post-HTx survival was assessed using Cox proportional hazards models. <h3>Results</h3> A total of 2696 HTx recipients were included in this study. Median ischemic time was 3.5 hours (interquartile range 2.8-4.0). 180-day post-HTx survival was 94.4% for recipients with IT <2.8 hours (quartile 1), 93.5% for IT between 2.8 and 3.5 hours (quartile 2), 93.6% for IT between 3.5 and 4.0 hours (quartile 3), and 91.4% for IT >4 hours (quartile 4) (log-rank <i>p</i>=0.15) (Figure 1). Compared to quartile 1, quartiles 2 and 3 achieved similar post-HTx survival (quartile 2: aHR 1.21, 95% CI 0.78-1.88, <i>p</i>=0.41; quartile 3: aHR 1.24, 95% CI 0.80-1.93, <i>p</i>=0.337), although hazard of death was significantly higher in quartile 4 (aHR 1.55, 95% CI 1.02-2.35, <i>p</i>=0.04). <h3>Conclusion</h3> HTx recipients with IT greater than 4 hours may be at higher risk of mortality under the new donor heart allocation system. Offers with longer IT require careful consideration for acceptance.

The Impact of Obesity and LVAD-Bridging on Heart Transplant Candidate Outcomes: A Linked STS INTERMACS - UNOS Data Analysis

<h3>Purpose</h3> Limited data integrating waitlist and post-heart transplant (HT) mortality have evaluated outcomes of LVAD-bridged strategy vs no LVAD based on patient characteristics. We aimed to evaluate waitlist and post-HT mortality in bridged in comparison to non-bridged patients based on body mass index (BMI). <h3>Methods</h3> We included adults listed for HT in UNOS and patients receiving durable LVAD as bridge to HT or candidacy in STS/INTERMACS databases (2010-2019). Using patient identifiers, we linked both databases. We categorized patients as underweight (BMI <18.5 kg/m²), normal weight (BMI 18.5-24.99 kg/m²), overweight (BMI 25-29.99 kg/m²) and obese (BMI ≥30 kg/m²). We assessed the effect of bridged and non-bridged strategy by BMI on waitlist mortality, HT probability and post-HT mortality. We used Kaplan-Meier analysis and log-rank test to compare risk across BMI classes, and competing risk and multivariable Cox PH models to assess the effect for each BMI class. <h3>Endpoints</h3> We included 12,761 LVAD-bridged and 17,518 non-bridged candidates. Bridged vs non-bridged patients were more frequently obese (37.2 vs 28.7%) or underweight (3.6 vs 2.6%) (p<0.001). In competing risk analysis, bridged compared to non-bridged patients had a lower rate of HT and higher waitlist mortality (Fig 1A,B). Multivariable analysis stratified by BMI showed increased waitlist mortality in bridged vs non-bridged overweight (HR 1.29 95%CI 1.09, 1.52) and obese patients (HR1.39 95%CI 1.18, 1.65) (Fig 1C) and similar risk in normal and underweight patients. LVAD-bridged patients had higher waitlist mortality and lower HT probability in comparison to non-bridged in overweight and obese patients. We will next integrate these results with post-HT survival in the linked STS-INTERMACS/UNOS cohort to provide further insights into the strategy most likely to lead to survival benefit based on BMI and determine whether the current guideline recommendation of using LVAD as a bridge to weight loss should be re-examined.

Hepatorenal dysfunction assessment with the Model for End-Stage Liver Disease Excluding INR score predicts worse survival after heart transplant in pediatric Fontan patients

BackgroundFontan physiology results in multiorgan dysfunction, most notably affecting the liver and kidney. We evaluated the utility of Model for End-Stage Liver Disease Excluding INR (MELD-XI) score, a score evaluating the function of both liver and kidney to identify Fontan patients at increased risk for morbidity and mortality post–heart transplant. MethodsThe Pediatric Heart Transplant Society database was queried to identify Fontan patients listed for heart transplant between January 2005 and December 2018. MELD-XI scores were calculated at listing and heart transplant. A multivariable analysis was conducted to identify risk factors for post–heart transplant mortality. Demographic, clinical characteristics, and survival differences were evaluated and compared between the high and low MELD-XI score cohorts. The impact of changing MELD-XI scores during the waitlist period on post–heart transplant outcomes was also evaluated. ResultsOf 565 Fontan patients who underwent transplantation, 524 (93%) had calculable MELD-XI scores at the time of heart transplant: 421 calculable at listing and 392 calculable at listing and at heart transplant. On multivariable analysis, only MELD-XI score (squared) (hazard ratio, 1.007), history of protein-losing enteropathy (hazard ratio, 2.1), and ventricular assist device use at transplant (hazard ratio, 3.4) were risk factors for early phase post–heart transplant mortality. Patients with high MELD-XI scores at heart transplant had inferior survival post–heart transplant (P = .02); those in the high MELD-XI score cohort at wait listing and heart transplant tend to have the worst post–heart transplant survival; however, this was not significant (P = .42). ConclusionsThe MELD-XI, an easily calculated score, serves as a valuable aid in identifying pediatric Fontan patients at increased risk for post–heart transplant mortality.

Multiorgan procurement is associated with a survival benefit after heart transplantation.

We assessed the impact of donor multiorgan procurement on survival following orthotopic heart transplantation (OHT). From the UNOS STAR database, we included all adult (≥18Y) heart transplants (OHT) performed since 2000 and used donor IDs to determine how many other organs were procured from the same donor as the recipient's heart allograft (regardless of recipient). The Kaplan-Meier survival functions and risk-adjusted Cox proportional hazards regression models were computed to assess the association of multiorgan procurement with post-heart transplantation mortality. We included 40336 OHT patients. Including the heart, the median number of donor organs procured was 3 (IQR, 3-4). Heart donors underwent liver procurement in 89.7%; kidney(s) in 98.1% (single 95%, bilateral 5%); lung(s) in 38.0% (single 28%, bilateral 72%); pancreas in 10.4%; and intestine in 1.6%. Following risk adjustment across 16 recipient- and donor-specific variables, an increasing number of organs procured were independently associated with reduced post-OHT mortality (HR 0.98, 95% CI 0.96-0.99, P=.025). Though no significant associations were found examining specific organ types, double lung procurement trended toward a protective effect (HR 0.96, 0.92-1.01, P=.086), with counts of non-lung organs procured still bordering on significance (HR 0.97, 95% CI 0.95-1.00, P=.067). These results likely reflect improved multiorgan donor quality.

Impact of Multiorgan Procurement on Survival Following Heart Transplantation

Patient and donor risk factors for post-heart transplant mortality have been identified, but the relevance of the procurement procedure itself has not been examined. We sought to assess the impact of donor multiorgan procurement on survival following orthotopic heart transplantation (OHT). From the UNOS STAR database, we included all adult (≥18Y) heart transplants (HT) performed since 2000 and used donor IDs to determine how many other organs were procured from the same donor as the recipient's heart allograft (regardless of recipient). Kaplan-Meier survival functions and risk-adjusted Cox proportional hazards regression models were computed to assess the association of multiorgan procurement with post-heart transplantation mortality. We included 40,336 HT patients. Including the heart, the median number of donor organs procured was 3 (IQR, 3-4). Heart donors underwent liver procurement in 89.7%; kidney(s) in 92.5% (single 95%, bilateral 5%); lung(s) in 38.0% (single 28%, bilateral 72%); pancreas in 10.4%; and intestine in 1.6%. Only 4.5% were multiorgan transplants (i.e., to the same recipient as the heart) - heart/kidney in 1,561 patients and heart/liver in 276. Following risk adjustment across 16 recipient and donor variables, an increasing number of organs procured was independently associated with reduced post-HT mortality (HR 0.92, 95% CI 0.95-0.99, p=0.008). Lung procurement was independently associated with reduced post-HT mortality (HR 0.96, 0.92-0.99, p=0.04), but not liver, kidney, pancreas, or intestine procurement. The protective association with lung procurement appeared to be driven by bilateral (HR 0.94, 0.88-1.01, p=0.07) versus single lung procurement. An increasing number of organs procured from a donor is independently associated with improved survival after heart transplantation. Lung procurement demonstrated a significant protective association. These results may reflect that healthier donors are more likely to be multiorgan donors.

Pre-Heart Transplant Glomerular Filtration Rate and Outcome

Heart transplantation remains the optimal treatment for end-stage heart failure. Renal insufficiency has long been considered a significant risk factor for post-heart transplant morbidity and mortality. The International Society of Heart and Lung Transplantation has suggested glomerular filtration rate (GFR) cutoffs of <40mL/min and <30mL/min in 2006 and 2016 respectively. We sought to assess our transplant patients with respect to baseline pre-transplant GFR METHODS: Between 2010 and 2018 we assessed 534 heart transplant patients and divided them based on the GFR directly before transplant. Groups were divided into GFR<30 (n=53), GFR 30-60 (n=299) and GFR>60 (n=182). All combined heart-kidney transplantations were excluded from this study. Endpoints included 1 and 5 year survival, freedom from the development of cardiac allograft vasculopathy (CAV) (as defined by stenosis ≥ 30% by angiography), non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), any treated rejection (ATR), acute cellular rejection (ACR), antibody-mediated rejection (AMR). There is no overall significant difference between the groups in terms of 1,3 or 5 year survival, 1-year freedom from CAV, NF-MACE and all rejection. However, the GFR<30 group had a significantly lower 5-year survival than the GFR>60 group, 73.6% vs. 86.8%. GFR did not greatly improve at 1-year post-transplant for any group. Heart transplantation in patients with pre-transplant GFR <30 appears to have acceptable 1-year outcomes. However, these patients have worse long-term survival and should be considered for combined heart-kidney transplant.

Cardiac Transplantation Outcomes in Patients with Amyloid Cardiomyopathy

Objective Amyloid cardiomyopathy (ACM) is a progressive and life-threatening disease characterized by abnormal proteinaceous deposits within the cardiac extracellular space. The most common forms of ACM are caused by immunoglobulin derived light chains (AL) and transthyretin (TTR). Although the management for each entity is different, heart transplant (HT) remains the definitive treatment for patients who progress to end stage heart failure. To date there is no consensus regarding the usage of heart transplantation in patients with ACM, and studies have shown mixed results. In this study, we perform a contemporary multi-center analysis evaluating post HT survival in patients with ACM. Methods We conducted a multi-center analysis of 62588 adult HT recipients captured in the United Network for Organ Sharing (UNOS) registry from 1987-2018. Patients were characterized as ACM or Non-ACM. Baseline characteristics were obtained, and summary characteristics were calculated. Outcomes of interest included post-transplant survival, infection, treated rejection, and the ability to return to work. Unadjusted associations between ACM and non-ACM survival were determined using the Kaplan-Meier estimations and confounding was addressed using multivariable Cox proportional hazards models. Results 398 patients with a diagnosis of ACM were identified. ACM patients were older (61 vs 52 p= Conclusion In this analysis of HT in ACM, ACM was associated with a higher likelihood of post HT mortality. No differences were observed in episodes of treated rejection, hospitalization for infection or likelihood to return to work for income. Further analysis is warranted to establish the mechanism of higher mortality in ACM patients.

The effect of pre-heart transplant body mass index on posttransplant outcomes: An analysis of the ISHLT Registry Data.

We evaluated the effect of pre-heart transplant body mass index (BMI) on posttransplant outcomes using the International Society for Heart and Lung Transplantation Registry. Kaplan-Meier analysis and a multivariable Cox proportional hazard regression model were used for all-cause mortality, and cause-specific hazard regression for cause-specific mortality and morbidity. We assessed 38498 recipients from 2000 to 2014 stratified by pretransplant BMI. Ten-year survival was 56% in underweight, 59% in normal weight, 57% in overweight, 52% in obese class I, 54% in class II, and 47% in class III patients (P<0.001). Mortality was increased in underweight (HR 1.29, 95% CI 1.24-1.35), obese class I (HR 1.19, 95% CI 1.13-1.26), class II (HR 1.20, 95% CI 1.08-1.32), and class III patients (HR 1.45, 95% CI 1.15-1.83). Obesity was independently associated with increased death from myocardial infarction, chronic rejection, infection, and renal dysfunction. An underweight BMI lead to increased death from infection, acute and chronic rejection, malignancy, and bleeding. Obese patients had a higher incidence of renal dysfunction, diabetes, stroke, acute rejection, cardiac allograft vasculopathy, and malignancy, and underweight recipients had increased acute rejection. We have shown that pretransplant obese and underweight patients have increased post-heart transplant mortality and morbidity. This has implications for candidate selection and posttransplant management.

Incidence of Malignancies in Patients Treated With Sirolimus Following Heart Transplantation

BackgroundMalignancy is a major cause of late post-heart transplantation (HT) mortality. Sirolimus (SRL) exerts antiproliferative properties and its long-term use in HT as primary immunosuppression (IS) is associated with decreased mortality risk that is not fully explained by attenuation of cardiac allograft vasculopathy progression. ObjectivesThis study sought to examine whether conversion from calcineurin inhibitor (CNI)-based to SRL-based IS was associated with decreased risk of malignancy post-HT. MethodsOverall, 523 patients underwent HT between 1994 and 2016 at a single institution. The main outcomes included incidence of overall de novo malignancies (excluding non-melanoma skin cancers [NMSCs]), post-transplantation lymphoproliferative disorders (PTLD), and first and subsequent primary occurrences of NMSC post-HT. ResultsThe study identified 307 patients on SRL-based and 216 on CNI-based maintenance IS. Over a median follow-up of 10 years after HT, overall de novo malignancies (non-NMSC) occurred in 31% of CNI patients and in 13% of SRL patients (adjusted hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.18 to 0.62; p < 0.001). The incidence of the first NMSC was similar in the SRL and CNI groups (HR: 0.92; 95% CI: 0.66 to 1.28; p = 0.62). However, conversion to SRL was significantly associated with a decreased risk of subsequent primary occurrences of NMSC compared with that of CNI (adjusted HR: 0.44; 95% CI: 0.28 to 0.69; p < 0.001). The adjusted PTLD risk was significantly decreased in the SRL group (HR: 0.13; 95% CI: 0.03 to 0.59; p = 0.009). Late survival post-HT was markedly decreased in patients who developed non-NMSC, PTLD, or non-PTLD compared with patients who did not develop these malignancies, whereas NMSC had no significant effect on survival. ConclusionsConversion to SRL was associated with a decreased risk of all de novo malignancies, PTLD, and subsequent primary occurrences of NMSC after HT. These findings provided further explanation of the late survival benefit with long-term SRL use.

Impact of donor variables on heart transplantation outcomes in mechanically bridged versus standard recipients†.

This study aimed to quantify the impact of donor variables on post-heart transplantation mortality and morbidity in recipients with and without a pretransplant left ventricular assist device (LVAD). This is a prospective cohort study of the ISHLT Transplant Registry that includes all primary heart transplants in adult recipients (January 2005-June 2013, n = 15532). All recipients were divided into patients with a durable continuous-flow LVAD (LVAD recipient, n = 3315) and without mechanical support (standard recipient, n = 12217). Donors were classified as high risk (n = 3751) and low risk (n = 11781). Transplants were categorized into low-risk donor/standard recipient (n = 9214), high-risk donor/standard recipient (n = 3003), low-risk donor/LVAD recipient (n = 2567) and high-risk donor/LVAD recipient (n = 748). Outcomes prior to discharge, survival at 5 years and freedom from complications were computed for each group. LVAD recipients experienced more episodes of infection, stroke and acute rejection with both low- (P < 0.001, P < 0.001, P < 0.001) and high-risk donors (P < 0.001, P = 0.008, P = 0.028) prior to transplant discharge. Within standard recipients, a higher rate of primary graft failure (P = 0.035), infection (P = 0.001), dialysis (P = 0.012), acute rejection (P = 0.037) and less freedom from cardiac allograft vasculopathy (P < 0.001) and malignancy (P = 0.004) was observed with high-risk donors. Within LVAD recipients, no differences in complications prior to discharge or long-term morbidity were detected between low- and high-risk donors. When compared to standard recipient/low-risk donors, all the 3 remaining categories had an increased probability of death or graft failure within 90 days: LVAD recipient/low-risk donor [hazard ratio (HR) 1.26, confidence interval (CI) 1.05-1.51; P = 0.012], standard recipient/high-risk donor (HR 1.47, CI 1.27-1.71; P < 0.001) and LVAD recipient/high-risk donor (HR 1.72, CI 1.32-2.24; P < 0.001). Between 90 days and 5 years, only standard recipient/high-risk donor had an increased probability of death or graft failure (HR 1.140, CI 1.020-1.274; P = 0.021) when compared to standard recipient/low-risk donor. LVAD recipients, whether with high- or low-risk donors, have worse early (but not late) survival and more early complications than those of standard recipients. We found that adverse donor characteristics are less predictive for determining the outcome of LVAD-bridged recipients than standard recipients.

Impact of pretransplant recipient body mass index on postheart transplant mortality: A systematic review and meta-analysis.

The ISHLT's 2016 Guidelines on the selection of heart transplant (HT) candidates recommends weight loss prior to listing for persons with body mass (BMI) index greater than 35kg/m2 . We conducted a systematic review to assess the impact of BMI on all-cause mortality. We searched to identify eligible observational studies that followed HT recipients. We used the GRADE system to quantify absolute effects and quality of evidence, and meta-analyzed survival curves to assess post-transplant mortality across BMI categories. We found a significantly increased risk of mortality in patients with BMI>30kg/m2 across all age categories, independently of transplant era and study source (BMI 30-34.9: HR 1.10, 95% CI 1.04-1.17; BMI≥35: HR 1.24, 95% CI 1.12-1.38). We also found an increased risk of death in underweight (BMI<18.5kg/m2 ) candidates over 39years of age (Age 40-65: HR 1.24, 95% CI 1.02-1.53; Age>65: HR 1.70, 95% 1.13-2.57). We found obesity and underweight BMI to be associated with mortality post-HT. The similar and overlapping increased risk of mortality in patients with BMI 30-34.9 and BMI≥35 does not support the recently updated ISHLT guidelines. Future evidence in the form of randomized controlled trials is required to assess effectiveness of interventions targeting obesity-related comorbidities and weight management.