Mortality In Heart Transplant Recipients Research Articles

Association of Size Matching Using Predicted Heart Mass With Mortality in Heart Transplant Recipients With Obesity or High Pulmonary Vascular Resistance

Pretransplant obesity and higher pulmonary vascular resistance (PVR) are risk factors for death after heart transplant. However, it remains unclear whether appropriate donor-to-recipient size matching using predicted heart mass (PHM) is associated with lower risk. To investigate the association of size matching using PHM with risk of death posttransplant among patients with obesity and/or higher PVR. All adult patients (>18 years) who underwent heart transplant between 2003 and 2022 with available information using the United Network for Organ Sharing cohort database. Multivariable Cox models and multivariable-adjusted spline curves were used to examine the risk of death posttransplant with PHM matching. Data were analyzed from October 2022 to March 2023. Recipient's body mass index (BMI) in categories (<18.0 [underweight], 18.1-24.9 [normal weight, reference], 25.0-29.9 [overweight], 30.0-34.9 [obese 1], 35-39.9 [obese 2], and ≥40.0 [obese 3]) and recipient's pretransplant PVR in categories of less than 4 (29 061 participants), 4 to 6 (2842 participants), and more than 6 Wood units (968 participants); and less than 3 (24 950 participants), 3 to 5 (6115 participants), and 5 or more (1806 participants) Wood units. All-cause death posttransplant on follow-up. The mean (SD) age of the cohort of 37 712 was 52.8 (12.8) years, 27 976 (74%) were male, 25 342 were non-Hispanic White (68.0%), 7664 were Black (20.4%), and 3139 were Hispanic or Latino (8.5%). A total of 12 413 recipients (32.9%) had a normal BMI, 13 849 (36.7%) had overweight, and 10 814 (28.7%) had obesity. On follow-up (median [IQR] 5.05 [0-19.4] years), 12 785 recipients (3046 female) died. For patients with normal weight, overweight, or obese 2, receiving a PHM-undermatched heart was associated with an increased risk of death (normal weight hazard ratio [HR], 1.20; 95% CI, 1.07-1.34; overweight HR, 1.12; 95% CI, 1.02-1.23; and obese 2 HR, 1.07; 95% CI, 1.01-1.14). Moreover, patients with higher pretransplant PVR who received an undermatched heart had a higher risk of death posttransplant in multivariable-adjusted spline curves in graded fashion until appropriately matched. In contrast, risk of death among patients receiving a PHM-overmatched heart did not differ from the appropriately matched group, including in recipients with an elevated pretransplant PVR. In this cohort study, undermatching donor-to-recipient size according to PHM was associated with higher posttransplant mortality, specifically in patients with normal weight, overweight, or class II obesity and in patients with elevated pretransplant PVR. Overmatching donor-to-recipient size was not associated with posttransplant survival.

Coronary Collateral Circulation: A New Predictor of Mortality in Heart Transplant Recipients With Allograft Vasculopathy.

One hundred twenty-one patients receiving HT at our institution were retrospectively evaluated and were included if transthoracic echocardiography with coronary flow velocity reserve (CFVR) assessment and coronary angiography were performed. CMD was defined as CFVR of ≤2.5. Patients with CAV were enrolled, and their angiograms were reviewed to evaluate the presence of CCAs. Cardiovascular mortality was assessed as the main clinical outcome. Forty patients were found to have CCAs. Patients with CCAs have lower CFVR than those without CCAs (2.22 ± 0.72 versus 2.69 ± 0.92;P = 0.003), reflecting in different rates of CMD in the 2 groups (72.5% versus 37%; P < 0.001). CMD is associated with higher CAV grades (P < 0.001), which are also associated with CCAs (P < 0.001). Patients with poorly developed CCAs have lower CFVR (P < 0.001). At multivariable analysis, CMD (P = 0.008) and higher CAV grades (P = 0.005) are independent predictors of CCAs. During the median follow-up time of 10.2 (6.6-13.3) y, patients with CCAs have been found to have higher mortality than those without CCAs (57.5% versus 32.1%; P = 0.007). CCAs are associated with a lower probability of survival also in patients with CMD (P < 0.001) and are independent predictors of mortality (P < 0.001). Our results demonstrate an interplay between CAV, CMD, and CCAs. We confirm that CAV is associated with CMD, and we show, for the first time, that CMD is associated with CCAs. CCAs are pathophysiologically associated with more severe graft vasculopathy and independently predict mortality after HT.

Association of fasting blood glucose variability with all-cause mortality in heart transplant recipients.

Fasting blood glucose (FBG) variability, an emerging marker of glycemic control, has been shown to be related to the risk of cardiovascular events and all-cause mortality in subjects with or without diabetes. However, whether FBG variability is independently associated with a higher all-cause mortality in heart transplant recipients remains unknown. We performed a retrospective cohort study including 373 adult recipients who survived for at least 1year after heart transplantation with a functioning graft and measured FBG more than three times within first year after transplantation. Multivariable adjusted Cox regression analyses were performed to assess the association between FBG variability and all-cause mortality. Patients were categorized into three groups according to the coefficient of variation of FBG level: ≤7.0%, 7.0%-13.5%, and >13.5%. During a median follow-up of 44.4months (interquartile range [IQR], 22.6-63.3months), 31 (8.3%) participants died. In univariate analyses, FBG variability was associated with an increased all-cause mortality (hazard ratio [HR]: 3.00, 95% confidence interval [CI]: 1.67, 5.38; p<.001). This association remained materially unchanged in the multivariable model adjusted for components of demographics, cardiovascular history and lifestyle, hospital information, immunosuppressive therapy, and post-transplant renal function (HR: 2.75, 95% CI: 1.43, 5.28; p=.004). After heart transplantation, high FBG variability is strongly and independently associated with an increased risk of all-cause mortality. Our findings suggest that FBG variability is a novel risk factor and prognostic marker for heart transplantation recipients in outpatient clinic.

Risk Factors Associated With COVID-19 Mortality in Heart Transplant Recipients: A United Network for Organ Sharing Database Analysis.

Risk Factors Associated With COVID-19 Mortality in Heart Transplant Recipients: A United Network for Organ Sharing Database Analysis.

Overcoming challenges in patient selection and monitoring in combined heart and kidney transplantation.

Combined heart-kidney transplantation (HKT) is a growing therapeutic strategy in patients with advanced heart failure (HF) and concomitant chronic kidney disease (CKD). Although patients with advanced HF and need for chronic haemodialysis have a clear indication for combined HKT, challenges to current practice lie in identifying those patients with severely depressed kidney function, which will not recover kidney function after restoration of appropriate haemodynamic conditions following heart transplantation (HT) alone. Because of the paucity of available organs, maximisation of kidney graft utility whilst minimising the operative risks associated with combined transplantation is mandatory. The benefits of HKT go beyond the mere restoration of kidney function. Data from registry analysis show that HKT improves overall survival in patients with CKD, as compared to heart transplant only, and it is associated with reduced incidence of heart allograft rejection, likely through the promotion of host immune tolerance mechanisms. In patients not requiring chronic dialysis, kidney-after-heart strategy may be explored, instead of combined HKT, in particular when the aetiology of CKD is unclear. This indeed allows for monitoring and gaging of indications for combined transplantation in the postoperative period. This approach however should be matched with priority listing for kidney transplantation given the high waitlist mortality in heart transplant recipients with associated CKD. The use of kidney machine perfusion may represent an additional tool to optimise the outcome of HKT, allowing more time to stabilise the patient after HT surgery.

Invasive Aspergillosis Manifesting As An Intracardiac Mass In A Heart Transplant Patient

<h3>Introduction</h3> Invasive aspergillosis (IA) is the third most common form of invasive fungal infections in immunocompromised patients, and has the second highest mortality rate at 30-70%. Invasion of lung parenchyma is the most common presentation, but can rarely present as aspergillus endocarditis. To our knowledge, IA presenting as a mass lesion in the heart is very rare and has never been reported in an orthotopic heart transplant (OHT) patient. We present a case of invasive aspergillus manifesting as an intracardiac mass in the right atrium (RA) in a heart transplant patient who survived. <h3>Patient presentation</h3> This is a 68 year-old-male with ischemic cardiomyopathy s/p OHT in June 2019 complicated by Aspergillus fumigatus sternal osteomyelitis requiring complete sternectomy on chronic antifungal therapy who was readmitted for right shoulder pain and failure to thrive. On admission, the patient was afebrile and hemodynamically stable. Pertinent workup showed transthoracic echocardiogram (TTE) with right atrial (RA) mass confirmed to be 3.5 × 3.3 cm by transesophageal echocardiogram (TEE) attached to interatrial septum. Initial malignancy workup was negative. Further infectious work up was remarkable for Aspergillus antigens. Intra-cardiac echocardiogram (ICE) and TEE techniques were utilized to locate and culture the mass. Argon epitome was placed into the mass under fluoroscopic and intracardiac echo guidance, extracting two specimens. Gross examination suggested identical specimens without any evidence of endocardium or lipomatous tissue. Initial pathology showed findings consistent with a thrombus but no evidence of fungal organisms, inflammation or malignancy. However, cultures from the specimen revealed Aspergillus fumigatus. Unfortunately, the patient was deemed a poor surgical candidate for resection due to other comorbidities and attempts are being made for long term antifungal therapy in management. <h3>Discussion</h3> Opportunistic infections such as invasive fungal infections are the leading cause of mortality in heart transplant recipients. Approximately 65% of OHT cases will have an infection within the first year of surgery. In a single institution, both incidence and mortality of IA in heart transplant recipients declined over the years. Despite this decrease, it remains a common pathogen observed in immunocompromised populations, specifically in solid organ transplantations. Most IA present as pulmonary disease as the route of entry for aspergillus conidia particles is inhalation, but rarely has intracardiac manifestations. To our knowledge, this is the first case report of invasive aspergillosis in a heart transplant recipient who had rare systemic manifestations including intra-cardiac mass and sternal osteomyelitis.

Incidence and Severity of Cytomegalovirus Infection in Seropositive Heart Transplant Recipients

<h3>Purpose</h3> Cytomegalovirus (CMV) infection contributes to morbidity and mortality in heart transplant recipients (HTR). Donor positive, recipient negative (D+/R-) patients are high risk and generally receive antiviral prophylaxis. The burden of CMV infection in recipient seropositive (R+) HTR is less clear, with preventative recommendations mostly extrapolated from other solid organ transplant groups. The aim of this retrospective cohort study was to define the incidence, severity of & risk factors for CMV infection in R+ HTR. <h3>Methods</h3> CMV seropositive HTR were included (2010-2019). Antiviral prophylaxis was not routinely used, with clinical monitoring the local standard of care. Data were collected from medical records, & patients followed for a year post-transplant. The incidence of CMV infection, including tissue invasive disease, was quantified, & predisposing/mitigating factors identified. We also assessed the association of CMV with adverse outcomes including prolongation of hospitalization & death. <h3>Results</h3> Our cohort included 155 R+ HTR (median age 53yrs, 72% male, 56% D+/R+, 68% basiliximab & 8% thymoglobulin induction). Valganciclovir prophylaxis was used in 35 (23%) for a median of 103 days (IQR 78-222). CMV infection occurred in 27 (17%) patients at a median onset of 67 days (41-124), median peak viral load was 1250 IU/mL (221-6539) & 18/27 (67%) required readmission. End-organ disease occurred in 22 (82%) & was most commonly gastrointestinal (52%). CMV infection was associated with a longer length of stay (27 vs. 20 days, HR 1.02, 95% CI 1.00-1.03, p=0.02), higher rate of intensive care readmission (26% vs. 9%, 4.57, 1.76-11.88, p=0.002), & increased mortality (33% vs. 8%, HR 9.11, 3.49-23.8, p<0.001). Valganciclovir prophylaxis was protective for CMV (4% vs. 27%, 0.094, 0.012-0.75, p=0.025), even though patients receiving it were more likely to have had thymoglobulin induction (31% vs. 2%, OR 27.04, 5.63-129.88, p<0.001). <h3>Conclusion</h3> CMV infection occurred in 17% of R+ HTR & was associated with a high burden of disease, worse post-transplant outcomes & increased mortality. Patients who received valganciclovir prophylaxis were less likely to develop CMV infection. These findings support the routine use of CMV preventative strategies such as antiviral prophylaxis following heart transplantation in all CMV R+ patients.

Variability in Donor-Derived Cell-Free DNA Scores to Predict Mortality in Heart Transplant Recipients - A Proof-of-Concept Study.

BackgroundOver the last decade, expanding use of molecular diagnostics in heart transplantation has allowed implementation of non-invasive surveillance strategies for monitoring allograft health. The commercially available HeartCare platform combines the AlloMap gene expression profiling assay and the AlloSure donor-derived cell-free DNA test (dd-cfDNA). Beyond their established use for assessment of rejection, evidence is building for predictive utility, with the longitudinal AlloMap Variability score previously shown to correlate with the risk of future rejection, graft dysfunction, re-transplantation, or death. In this single-center, retrospective pilot study, we evaluated the performance of a novel AlloSure Variability metric in predicting mortality in a cohort of heart transplant recipients.MethodsSeventy-two adult heart transplant recipients with at least 3 concurrent AlloMap/AlloSure results were included. Demographic, clinical, imaging, and laboratory parameters were captured. Variability was defined as the standard deviation of longitudinal AlloMap/AlloSure results. A Cox multivariable adjusted proportional hazards model was used to evaluate the variability metrics as predictors of mortality. Associations between AlloMap/AlloSure variability and donor specific antibody (DSA) status were also assessed.ResultsA total of 5 patients (6.9%) died during a median follow-up of 480 days. In a univariate Cox proportional hazards model, higher AlloSure variability (HR 1.66, 95%CI 1.14 – 2.41), but not AlloMap variability or the cross-sectional AlloSure/AlloMap results was associated with increased mortality risk. Longitudinal AlloSure variability was also higher among patients with both preformed DSA and those developing de novo DSA.ConclusionOur results suggest that increased variability of dd-cfDNA in heart transplant patients is associated with both mortality risk and the presence of donor specific antibodies. These findings highlight the added value of longitudinal data in the interpretation of AlloMap/AlloSure scores in this population and open the door to larger studies investigating the utility of these metrics in shaping post-transplant clinical care paradigms.

Coronary allograft vasculopathy managed by Flash ostial balloon in a pediatric patient

Coronary allograft vasculopathy (CAV) is the most significant cause of morbidity and mortality in heart transplant recipients. Inflammation and endothelial dysfunction caused by graft rejection and viral infections leads to a combination of circumferential intimal fibromuscular hyperplasia, atherosclerosis, and inflammation affecting all layers of the vessel wall. Though obstructive CAV is often asymptomatic, posing a diagnostic challenge in post-transplant patients, early diagnosis and treatment aid faster recovery and improved outcomes. The role of percutaneous coronary intervention in the treatment of CAV is unknown and not well studied in the pediatric population. We present a first-in-human case of ostial left main coronary artery disease managed with flaring of the ostial coronary stent using a Flash ostial balloon in a pediatric patient with history of an orthotopic heart transplant.

Abstract 13306: Predictors of All-Cause Mortality in Heart Transplant Recipients With COVID-19

Introduction: Heart transplant recipients are among the most vulnerable to suffer complications from Covid-19, yet there remains no standard of treatment. The primary objective of this study was to identify predictors of all-cause mortality in heart transplant recipients infected with Covid-19 to better tailor management for these medically complex patients. Methods: A retrospective analysis of 28 heart transplant recipients with Covid-19 infections was performed at Loyola University Medical Center, a large tertiary care academic center located in the Chicago metropolitan area. Numerical data was assessed using two-tailed t-tests and bivariate logistical regression. Categorical variables were analyzed using chi-squared tests. Statistical analysis was performed using JMP Pro 15. Results: Between March 1, 2020 and April 30, 2021, 28 heart transplant recipients with Covid-19 sought care at our hospital. The inpatient cohort consisted of 19 patients, 10 (53%) of whom met the primary endpoint of all-cause mortality. Those in the mortality arm (mean age 58.7 ± 21.5 vs 54.3 ± 13.1 in survival arm, p=0.58) were more likely to present closer to symptom onset with an elevated RR, INR, lower MAP, cough, or ESRD. Patients admitted to an ICU with superimposed infections or shock, requiring antibiotics, vasopressors, dialysis, or convalescent plasma were more likely to meet the primary endpoint. Azathioprine appeared protective against all-cause mortality. Conclusions: This is the only known study to assess clinical outcomes in heart transplant recipients based in the American Midwest, a region with a high infection burden but equipped with commensurate clinical resources and access to evolving Covid-directed therapies. Our study demonstrated a considerably high mortality rate (53%) among heart transplant recipients with Covid-19 despite these measures. Further studies are warranted to identify key predictors of mortality in this population to guide management.

PTEN as a Therapeutic Target in Pulmonary Hypertension Secondary to Left-heart Failure: Effect of HO-3867 and Supplemental Oxygenation.

Pulmonary hypertension (PH) is a condition when the pressure in the lung blood vessels is elevated. This leads to increase in thickness of the blood vessels and increases the workload of the heart and lungs. The incidence and prevalence of PH has been on the increase in the last decade. It is estimated that PH affects about 1% of the global population and about 10% of individuals >65 years of age. Of the various types, Group 2 PH is the most common type seen in the elderly population. Fixed PH or PH refractive to therapies is considered a contraindication for heart transplantation; the 30-day mortality in heart transplant recipients is significantly increased in the subset of this population. In general, the pathobiology of PH involves multiple factors including hypoxia, oxidative stress, growth factor receptors, vascular stress, etc. Hence, it is challenging and important to identify specific mechanisms, diagnosis and develop effective therapeutic strategies. The focus of this manuscript is to review some of the important pathobiological processes and mechanisms in the development of PH. Results from our previously reported studies, including targeted treatments along with some new data on PH secondary to left-heart failure, are presented.

Impact of diabetes and chronic dialysis on post-transplant survival in combined heart-kidney transplant recipients.

Growing research supports an increased survival benefit of combined heart and kidney transplantation in patients with both heart and renal failure. As a result, the frequency of these combined transplants continues to increase. Despite this trend, little has been done to quantify the impact of chronic illness in this population. We identified adult recipients of combined heart-kidney transplant from the Scientific Registry of Transplant Recipients (SRTR) database between 2005 and 2018. We focused on renal disease secondary to diabetes and duration of dialysis as markers of chronic illness. The primary outcome was post-transplant mortality. Our final multivariable Cox proportional hazard model found that diabetes-associated renal disease (HR 1.57, 95% CI 1.14-2.15, p=.01) and dialysis duration (HR 1.08, 95% CI 1.01-1.15, p=.02) were significant predictors of post-transplant mortality. Given the significant impact of dialysis duration and renal disease secondary to diabetes mellitus, these chronically ill patients should be closely examined for conditions such as peripheral vascular disease and frailty, which have been shown to affect mortality in heart transplant recipients and are prevalent in the chronic dialysis population.

Depressive symptoms at 1 year after surgery increase the risk of cardiac allograft vasculopathy and mortality in heart transplant recipients: A prospective cohort study

ObjectiveTo investigate the impact of depressive symptoms at 1-year post-heart transplant (HTx) on cardiac allograft vasculopathy (CAV) and mortality. MethodsWe performed a single-center prospective cohort study of patients 1-year post-HTx consecutively enrolled between January 2001 and September 2015, and followed-up until November 2020. Kaplan-Meier and uni- and multivariate cox proportional hazards models were used to investigate the impact of depressive symptoms (Beck Depression Inventory) on all-cause mortality and clustered CAV events, i.e. time to angiographically detected CAV, revascularizations, retransplantation/CAV-mortality. Results23.7% (45/190) (median age 53.5 [IQR 19.3], 77% men) had mild to severe depressive symptoms (BDI 10–63). Forty-four patients (23.2%) died during a 10.4 years median follow-up. Depressive symptoms (BDI ≥ 10) increased all-cause mortality risk (HR = 2.52 [1.35–4.71], p = .004), even after adjusting for confounders (HR = 2.95 [1.50–5.80], p = .002). CAV data were available for 156 patients. During a 9.9 years median follow-up, 51 patients (32.7%) developed CAV or revascularization of which 8 received at least a second revascularization, 3 were re-transplanted, and 9 died from CAV-related causes. Analysis showed a significant increased CAV-risk among depressed patients (HR = 2.27 [1.10–4.69], p = .026), even in adjusted models (HR = 2.25 [1.01–4.98, p = .047). ConclusionDepressive symptoms at 1-year post-HTx unfavorably impact mortality and CAV, highlighting the need for interventions.

Coronary Flow Reserve Predicts Major Adverse Cardiac Events and All-Cause Mortality in Heart Transplant Recipients

<h3>Purpose</h3> Cardiac allograft vasculopathy (CAV) after heart transplantation (HTx) affects the epicardial arteries and veins and also the coronary microcirculation. In the absence of proximal epicardial artery stenosis, coronary flow velocity reserve (CFVR) reflects the function of the myocardial microcirculation. We aimed to determine the prognostic value of 1) CFVR and 2) a combination of CFVR and left ventricular global longitudinal strain (LVGLS) in HTx patients. <h3>Methods</h3> CFVR was evaluated using pulsed wave Doppler echocardiography in 98 HTx patients (median 6.9 years from HTx) examined with coronary angiography. Patients were enrolled from 2013 to 2018 and prospectively followed until June 1^st 2020. All-cause mortality and major adverse cardiac events (MACE) including heart failure, significant CAV progression, coronary intervention or cardiovascular death, were recorded. <h3>Results</h3> Median follow-up was 3.2 [interquartile range 1.9-5.1] years. Patients with low CFVR (<2.0, n=20) had a significantly reduced event-free survival rate compared with patients with high CFVR (≥2.0, n=78) (35% vs. 82%, hazard ratio (HR) 4.6, 95% CI 2.3-9.1, <i>p</i><0.0001) and had a higher rate of mortality than patients with high CFVR with an absolute difference of 43.3% (65.3% vs. 22.0%; HR 5.0, 95% CI 2.1-11.9, <i>p</i><0.0001). By combining low CFVR and low LVGLS magnitude (>-15.5%), we obtained a strong predictive model for MACE (HR 10.5, 95% CI 4.5-24.5, <i>p</i><0.0001) and all-cause mortality (HR 10.3, 95% CI 3.5-30.6, <i>p</i><0.001), which remained strong after adjustment for angiographic CAV. <h3>Conclusion</h3> CFVR strongly predicts MACE and all-cause mortality in HTx-patients. A model combining low CFVR and low LVGLS magnitude was a strong model for MACE and all-cause mortality prediction and could be considered as a non-invasive method for routine CAV surveillance.

Association between routine measures of graft function and mortality in heart transplant recipients

ObjectiveTo date, long-term graft dysfunction, an important cause of death after heart transplantation, has been defined as a left ventricular ejection fraction (LVEF) of ≤40% or right atrial pressure (RAP)...

Trajectories of Cardiac Allograft Vasculopathy After Heart Transplantation and association with mortality: a population-based study

Abstract Background Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant recipient's mortality. However, the associations between CAV trajectories and mortality remains poorly described. Purpose We aimed to identify the different evolutive profiles of CAV and to determine the respective association with all-cause mortality. Methods Heart transplant recipients receiving care at 4 academic centers were included. Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessment of clinical, functional, histological and immunological parameters. The mainoutcome was a prediction for CAV trajectories using unsupervised latent class mixed models. We then identified their association with all-cause mortality (NCT04117152). Results Overall, 1,301 patients were included (815 and 486 in the development and validation cohorts, respectively). The median follow-up post-transplant was 6.6 years (IQR=4.7) with 4,710 coronary angiographies analyzed (3.6±1.6 CAV assessments per patient). We identified 4 distinct profiles of CAV trajectories over 10 years that were characterized by i)Patients without CAV at baseline and non-progression (n=823, 63.3%), ii) patients without CAV at baseline and late onset CAV progression (n=79, 6.1%), iii) patients with mild baseline CAV and mild progression (n=261, 20.1), iv) patients with mild baseline CAV and accelerated CAV progression (n=138, 10.6%, discrimination 0.95). The 4 CAV trajectories showed gradient for all-cause mortality (p&amp;lt;0.001). Trajectories #3 and #4 were associated with higher mortality rates (10-year patient survival of 73.43% [95% CI 65.18–80.02] and 51.89% [95% CI 38.76–63.51], respectively) as compared with trajectories #1, and #2 that were characterized by 10-year patient survival of 80.01 [95% CI 76.38–84.82] and 83.49% [95% CI 71.34–90.80], respectively (p&amp;lt;0.001). Conclusion In a large multicentric and highly phenotyped prospective cohort of heart transplant recipients, we identified 4 robust CAV trajectories. These different profiles were associated with distinct prognosis. Our results provide the basis for a trajectory-based assessment of heart transplant patients for early patient risk stratification and patient monitoring. Figure 1. Overall 10-year survival probability according to the CAV trajectory in the overall cohort (n=1,301). The left part represents the main profiles CAV grades identified with latent class mixed models. Thick lines represent latent class trajectory; thin lines represent CAV individual patient trajectory. The right part represent the Kaplan Meier curves of the different trajectories. Funding Acknowledgement Type of funding source: None

Identification of trajectories of cardiac allograft vasculopathy after heart transplantation: a nationwide comparison

Abstract Background Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant recipient's mortality. However, little is known about CAV trajectories at a population level. Purpose We aimed to identify the different profiles of CAV trajectories. Methods Heart transplant recipients receiving care at 4 academic centers (2004 to 2016) were included. Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessment of clinical, functional, histological and immunological parameters. The mainoutcome was the CAV trajectories, identified with unsupervised latent class mixed models. Results Overall, 1,301 patients were included (609 in France, 206 in Belgium and 486 in the US). The median follow-up post-transplant was 6.6 years (IQR=4.7) with 4,710 coronary angiographies analyzed (3.6±1.6 CAV assessments per patient). In the French development cohort, we identified 4 distinct profiles of CAV trajectories over 10 years that were characterized by i) Patients without CAV at baseline and non-progression (n=317, 52.1%), ii) patients without CAV at baseline and late onset CAV progression (n=52, 8.5%), iii) patients with mild baseline CAV and mild progression (n=151, 24.8%), iv) patients with mild baseline CAV and accelerated CAV progression (n=89, 14.6%, discrimination 0.92). The 4 CAV trajectories were independently validated in the external validation cohorts from Belgium (discrimination=0.92) and the US (discrimination=0.97). Conclusion In a large multicentric and highly phenotyped prospective cohort of heart transplant recipients, we identified and validated 4 distinct CAV trajectories corresponding to specific initial CAV grades and subsequent evolutions. Our results provide the basis for a trajectory-based assessment for risk stratification at early-stage post heart transplantation. Figure 1. Cardiac allograft vasculopathy trajectories in France (n=609), in Belgium (n=206), in USA (n=486). Thick lines represent latent class trajectory; thin lines represent CAV individual patient trajectory. Funding Acknowledgement Type of funding source: None

Determinants of trajectories of cardiac allograft vasculopathy after heart transplantation: a population based study

Abstract Background Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant recipient's mortality. Little is known about determinants of CAV trajectories at a population level. Purpose We aimed to identify the respective contribution of immune and non-immune factors in the different evolutive profiles of CAV. Methods Heart transplant recipients receiving care at 2 academic centers (2004 to 2016) were included. Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessment of clinical, functional, histological and immunological parameters. The outcome was CAV trajectories, identified with unsupervised latent class mixed models. The independent, predictive factors of CAV trajectories were investigated with multinomial regressions (NCT04117152). Results Overall, 815 patients were included. The median follow-up post-transplant was 7.7 years (IQR=5.14) with 2,742 coronary angiographies analyzed. We identified 4 distinct profiles of CAV trajectories over 10 years that were characterized by i) Patients without CAV at baseline and non-progression (n=459, 56.3%), ii) patients without CAV at baseline and late onset CAV progression (n=62, 7.6%), iii) patients with mild baseline CAV and mild progression (n=188 23.1%), iv) patients with mild baseline CAV and accelerated CAV progression (n=106, 13.0%, discrimination 0.92). Six early independent predictors of CAV trajectories were identified: donor age (p&amp;lt;0.001), donor male gender (p&amp;lt;0.001), donor tobacco consumption (p=0.001), recipient post-transplant dyslipidemia (p=0.009), preexisting or de novo class II anti-HLA donor-specific antibodies (p=0.004) and episode of acute cellular rejection ≥2R during the first year post transplantation (p=0.028). Conclusion In a large multicentric and highly phenotyped prospective cohort of heart transplant recipients, we identified 4 robust CAV trajectories and their respective immune and non-immune determinants. Our results provide the basis for a trajectory-based assessment of heart transplant patients for early patient risk stratification and patient monitoring. Factors associated CAV trajectories in multivariate analyses in the derivation cohort. This table shows the association of clinical, immunological, functional and structural parameters associated with CAV trajectories in multivariate multinomial regression analysis. The trajectory of reference was trajectory #1, including patients with no CAV at baseline and stable CAV grade over time. Funding Acknowledgement Type of funding source: None

Beta-blocker therapy in heart transplant recipients: A review.

Beta-blockers are essential drugs for the treatment of many cardiovascular diseases, such as heart failure, acute and chronic ischemic heart disease, tachyarrhythmias, and hypertension. However, these drugs have not been used in cardiac transplant patients for many years owing to the fear that they could reduce cardiac output and functional capacity. In recent years, however, some evidence has shown that even in cardiac transplanted patients, β-blockers are useful and effective in the treatment of sinus tachycardia, supraventricular and ventricular tachyarrhythmias, left ventricular systolic dysfunction, and arterial hypertension. Furthermore, some data have shown that the use of β-blockers is associated with reduced mortality in heart transplant recipients. In this review, we summarize this evidence with particular emphasis on the practical aspects of the use of β-blockers in post-transplantation patients to promote the use of this important class of drugs in clinical practice.

Long-Term Outcomes and Risk Factors of Renal Failure Requiring Dialysis after Heart Transplantation: A Nationwide Cohort Study.

Acute kidney injury and renal failure are common after heart transplantation. We retrospectively reviewed a national cohort and identified 1129 heart transplant patients. Patients receiving renal replacement therapy after heart transplantation were grouped into the dialysis cohort. The long-term survival and risk factors of dialysis were investigated. Patients who had undergone dialysis were stratified to early or late dialysis for subgroup analysis. The mean follow-up was five years, the incidence of dialysis was 28.4% (21% early dialysis and 7.4% late dialysis). The dialysis cohort had higher overall mortality compared with the non-dialysis cohort. The hazard ratios of mortality in patients with dialysis were 3.44 (95% confidence interval (CI), 2.73–4.33) for all dialysis patients, 3.58 (95% CI, 2.74–4.67) for early dialysis patients, and 3.27 (95% CI, 2.44–4.36; all p < 0.001) for late dialysis patients. Patients with diabetes mellitus, chronic kidney disease, acute kidney injury, and coronary artery disease were at higher risk of renal failure requiring dialysis. Cardiomyopathy, hepatitis B virus infection, and hyperlipidemia treated with statins were associated with a lower risk of renal dysfunction requiring early dialysis. The use of Sirolimus and Mycophenolate mofetil was associated with a lower incidence of late dialysis. Renal dysfunction requiring dialysis after heart transplantation is common in Taiwan. Early and late dialysis were both associated with an increased risk of mortality in heart transplant recipients.