Enhancing the Prediction of Cardiac Allograft Vasculopathy Using Intravascular Ultrasound and Machine Learning: A Proof of Concept.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the leading cause of late graft dysfunction in heart transplantation. Building on previous unsupervised learning models, we sought to identify CAV clusters using serial maximal intimal thickness and baseline clinical risk factors to predict the development of early CAV. METHODS: This is a single-center retrospective study including adult heart transplantation recipients. A latent class mixed-effects model was used to identify patient clusters with similar trajectories of maximal intimal thickness posttransplant and pretransplant covariates associated with each cluster. RESULTS: Among 186 heart transplantation recipients, we identified 4 patient phenotypes: very low, low, moderate, and high risk. The 5-year risk (95% CI) of the International Society for Heart and Lung Transplantation-defined CAV in the high, moderate, low, and very low risk groups was 49.1% (35.2%-68.5%), 23.4% (13.3%-41.2%), 5.0% (1.3%-19.6%), and 0%, respectively. Only patients in the moderate to high risk cluster developed the International Society for Heart and Lung Transplantation CAV 2-3 at 5 years (P=0.02). Of the 4 groups, the low risk group had significantly younger female recipients, shorter ischemic time, and younger female donors compared with the high risk group. CONCLUSIONS: We identified 4 clusters characterized by distinct maximal intimal thickness trajectories. These clusters were shown to discriminate against the development of angiographic CAV. This approach allows for the personalization of surveillance and CAV-directed treatment before the development of angiographically apparent disease.

Cardiac allograft vasculopathy and survival in pediatric heart transplant recipients transitioned to adult care.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is an important cause of mortality after pediatric heart transplantation (HT) but there is a paucity of data regarding its incidence and impact on survival in pediatric recipients transitioned to adult care. METHODS: We conducted a retrospective review of consecutive pediatric HT patients from 1989 to 2017 at the Hospital for Sick Children who transitioned to adult care at ≥18 years at Toronto General Hospital. We evaluated the incidence of International Society of Heart and Lung Transplantation CAV grade ≥1 using competing risk models. We assessed the association between all-cause mortality and CAV using Cox proportional hazards and used Kaplan Meier methods to evaluate all-cause mortality stratified by CAV and transplant era (1989-2001, 2002-2017). RESULTS: Ninety-six patients were transitioned to adult care by January 2022, of which 53 underwent repeat coronary angiography as adults. CAV was newly diagnosed in 49% patients after transition to adult care. The overall incidence of CAV was 3.9 cases per 100 person-years. There was no difference in the adjusted incidence of CAV according to transplant era (subdistribution hazard ratios = 1.17, 95% confidence interval (CI) 0.54-2.66). CAV was associated with a higher risk of death in the early era (hazard ratio (HR) 10.29, 95% CI 2.16-49.96), but not in the recent era (HR 1.61, 95% 0.35-7.47). CONCLUSIONS: There is a role for continued CAV surveillance after the transition to adult care. The implications of diagnosing CAV after the transition to adult care require further study, particularly because the risk of death in pediatric HT recipients diagnosed with CAV in the more recent era may be attenuated compared to the earlier HT era.

Cardiac PET Myocardial Blood Flow Quantification Assessment of Early Cardiac Allograft Vasculopathy.

BACKGROUND: Positron emission tomography (PET) has demonstrated utility for diagnostic and prognostic assessment of cardiac allograft vasculopathy (CAV) but has not been evaluated in the first year after transplant. OBJECTIVES: The authors sought to evaluate CAV at 1 year by PET myocardial blood flow (MBF) quantification. METHODS: Adults at 2 institutions enrolled between January 2018 and March 2021 underwent prospective 3-month (baseline) and 12-month (follow-up) post-transplant PET, endomyocardial biopsy, and intravascular ultrasound examination. Epicardial CAV was assessed by intravascular ultrasound percent intimal volume (PIV) and microvascular CAV by endomyocardial biopsy. RESULTS: A total of 136 PET studies from 74 patients were analyzed. At 12 months, median PIV increased 5.6% (95% CI: 3.6%-7.1%) with no change in microvascular CAV incidence (baseline: 31% vs follow-up: 38%; P = 0.406) and persistent microvascular disease in 13% of patients. Median capillary density increased 30 capillaries/mm2 (95% CI: -6 to 79 capillaries/mm2). PET myocardial flow reserve (2.5 ± 0.7 vs 2.9 ± 0.8; P = 0.001) and stress MBF (2.7 ± 0.6 vs 2.9 ± 0.6; P = 0.008) increased, and coronary vascular resistance (CVR) (49 ± 13 vs 47 ± 11; P = 0.214) was unchanged. At 12 months, PET and PIV had modest correlation (stress MBF: r = -0.35; CVR: r = 0.33), with lower stress MBF and higher CVR across increasing PIV tertiles (all P < 0.05). Receiver-operating characteristic curves for CAV defined by upper-tertile PIV showed areas under the curve of 0.74 for stress MBF and 0.73 for CVR. CONCLUSIONS: The 1-year post-transplant PET MBF is associated with epicardial CAV, supporting potential use for early noninvasive CAV assessment. (Early Post Transplant Cardiac Allograft Vasculopahty [ECAV]; NCT03217786).

The design of studies testing the effectiveness of risk-guided care has many challenges: a scoping review addressing key considerations.

OBJECTIVES: Studies evaluating the effectiveness of care based on patients' risk of adverse outcomes (risk-guided care) use a variety of study designs. In this scoping review, using examples, we review characteristics of relevant studies and present key design features to optimize the trustworthiness of results. STUDY DESIGN AND SETTING: We searched five online databases for studies evaluating the effect of risk-guided care among adults on clinical outcomes, process, or cost. Pairs of reviewers independently performed screening and data abstraction. We descriptively summarized the study design and characteristics. RESULTS: Among 14,561 hits, we identified 116 eligible studies. Study designs included randomized controlled trials (RCTs), post hoc analysis of RCTs, and retrospective or prospective cohort studies. Challenges and sources of bias in the design included limited performance of predictive models, contamination, inadequacy to address the credibility of subgroup effects, absence of differences in care across risk strata, reporting only process measures as opposed to clinical outcomes, and failure to report benefits and harms. CONCLUSION: To assess the benefit of risk-guided care, RCTs provide the most trustworthy evidence. Observational studies offer an alternative but are hampered by confounding and other limitations. Reaching valid conclusions when testing risk-guided care requires addressing the challenges identified in our review.

Predicted Heart Mass: A Tale of 2 Ventricles.

BACKGROUND: Total predicted heart mass (PHM) is the recommended metric to assess donor-recipient size matching in patients undergoing heart transplantation. Separately measuring right ventricular (RV) and left ventricular (LV) PHM may improve risk prediction of 1-year graft failure. METHODS: Adult heart transplant recipients from the UNOS database from 2000 to 2018 were included in the study. LV and RV PHM were modeled as restricted cubic splines. The association with 1-year graft failure was determined using adjusted Cox regression. The risk reclassification of using both LV and RV PHM versus total PHM was assessed using the net reclassification index. RESULTS: A total of 34 976 recipients were included. We observed a U-shaped association between total PHM and 1-year graft failure, such that risk increased for hearts undersized by >15% and those oversized by more than 27%. Graft failure incrementally increased when LV PHM was undersized by more than 5% and when RV was oversized by >20%. There was 1.5-fold greater risk of graft failure for an LV undersized by >26% or an RV oversized by more than 40%. Using LV and RV PHM risk-assessment separately led to a net reclassification index=8.5% ([95% CI, 5.3%-11.7%], nonevent net reclassification index=9.1%, event net reclassification index=-0.6%). CONCLUSIONS: The association between donor-recipient PHM match and the risk of graft failure after heart transplantation can be further understood as risk attributable to LV undersizing and RV oversizing. Assessing LV and RV PHM separately instead of total PHM could further refine the methods used to match donors and recipients for heart transplantation, minimize the risk of 1-year graft failure, and increase the use of donor organs.

Fibrotic Plaque and Microvascular Dysfunction Predict Early Cardiac Allograft Vasculopathy Progression After Heart Transplantation: The Early Post Transplant Cardiac Allograft Vasculopathy Study.

BACKGROUND: Early cardiac allograft vasculopathy (CAV) prognostication is needed to improve long-term outcomes after heart transplantation. We characterized first year posttransplant coronary anatomic-physiologic alterations to determine predictors of early CAV progression. METHODS: Heart transplant recipients at 2 institutions (enrolled January 2018 to March 2021) underwent prospective evaluation 3 and 12-month posttransplant with angiography and left anterior descending artery intravascular ultrasound, optical coherence tomography, fractional flow reserve, coronary flow reserve, and index of microcirculatory resistance measurements. CAV progression was assessed by intravascular ultrasound change in percentage intimal volume from baseline to 12-month follow-up. RESULTS: Eighty-two patients (mean age, 51 years; 60% men) completed evaluation at mean 13.8 and 56.3 weeks posttransplant. Donor atherosclerosis (baseline intravascular ultrasound maximal intimal thickness, ≥0.5 mm) was evident in 50%. De novo (follow-up maximal intimal thickness, ≥0.5 mm) and rapidly progressive CAV (maximal intimal thickness, ≥0.5-mm increase from baseline) developed in 24% and 13%, respectively. On optical coherence tomography, baseline to follow-up median intimal volume increased 42% (0.58 mm3/mm), percentage intimal volume increased 44% (4.6%), vessel volume decreased 4% (-0.50 mm3/mm) and lumen volume decreased 9% (-1.02 mm3/mm); P<0.05 for all. Fibrotic plaque was the predominant morphology: baseline, 29% and follow-up, 50%. Coronary physiology was abnormal in 41% at baseline and 45% at follow-up, with 1 in 5 patients having microvascular dysfunction (index of microcirculatory resistance, ≥25). On multivariable linear regression analysis, recipient male sex, fibrotic plaque, and index of microcirculatory resistance were independent predictors of coronary disease progression. CONCLUSIONS: Fibrotic plaque on optical coherence tomography and index of microcirculatory resistance early posttransplant predict CAV progression in the first year of transplantation. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03217786.

Extracorporeal Membrane Oxygenation for Graft Dysfunction Early After Heart Transplantation: A Systematic Review and Meta-analysis.

INTRODUCTION: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a prevailing option for the management of severe early graft dysfunction. This systematic review and individual patient data (IPD) meta-analysis aims to evaluate (1) mortality, (2) rates of major complications, (3) prognostic factors, and (4) the effect of different VA-ECMO strategies on outcomes in adult heart transplant (HT) recipients supported with VA-ECMO. METHODS AND RESULTS: We conducted a systematic search and included studies of adults (≥18 years) who received VA-ECMO during their index hospitalization after HT and reported on mortality at any timepoint. We pooled data using random effects models. To identify prognostic factors, we analysed IPD using mixed effects logistic regression. We assessed the certainty in the evidence using the GRADE framework. We included 49 observational studies of 1477 patients who received VA-ECMO after HT, of which 15 studies provided IPD for 448 patients. There were no differences in mortality estimates between IPD and non-IPD studies. The short-term (30-day/in-hospital) mortality estimate was 33% (moderate certainty, 95% confidence interval [CI] 28%-39%) and 1-year mortality estimate 50% (moderate certainty, 95% CI 43%-57%). Recipient age (odds ratio 1.02, 95% CI 1.01-1.04) and prior sternotomy (OR 1.57, 95% CI 0.99-2.49) are associated with increased short-term mortality. There is low certainty evidence that early intraoperative cannulation and peripheral cannulation reduce the risk of short-term death. CONCLUSIONS: One-third of patients who receive VA-ECMO for early graft dysfunction do not survive 30 days or to hospital discharge, and one-half do not survive to 1 year after HT. Improving outcomes will require ongoing research focused on optimizing VA-ECMO strategies and care in the first year after HT.

Predicted heart mass for size matching in obese heart transplant donors and recipients.

INTRODUCTION: Predicted heart mass (PHM) was neither derived nor evaluated in an obese population. Our objective was to evaluate size mismatch using actual body weight or ideal body weight (IBW)-adjusted PHM on mortality and risk assessment. METHODS: We conducted a retrospective cohort study of adult recipients with BMI ≥30 kg/m2 or recipients of donors with BMI≥30 kg/m2 from the ISHLT registry. We used multivariable Cox proportional hazard models to evaluate 30-day and 1-year mortality. The two models were compared using net reclassification index. RESULTS: 10,817 HT recipients, age 55 (IQR 46-62) years, 23% female, BMI 31 kg/m2 (IQR 28-33) were included. Donors were age 34 (IQR 24-44) years, 31% female, and BMI 31 kg/m2 (IQR 26-34). There was a significant nonlinear association between mortality and actual PHM but not IBW-adjusted PHM. Undersizing using actual PHM was associated with higher 30-day and 1-year mortality (p < .01), not seen with IBW-adjusted PHM. Actual PHM better risk classified .6% (95% CI .3-.8) patients compared to IBW-adjusted PHM. CONCLUSION: Actual PHM can be used for size matching when assessing mortality risk in obese recipients or recipients of obese donors. There is no advantage to re-calculating PHM using IBW to define candidate risk at the time of organ allocation.

Sparing the Prod: Providing an Alternative to Endomyocardial Biopsies With Noninvasive Surveillance After Heart Transplantation During COVID-19.

Background: The COVID-19 pandemic has reduced access to endomyocardial biopsy (EMB) rejection surveillance in heart transplant (HT) recipients. This study is the first in Canada to assess the role for noninvasive rejection surveillance in personalizing titration of immunosuppression and patient satisfaction post-HT. Methods: In this mixed-methods prospective cohort study, adult HT recipients more than 6 months from HT had their routine EMBs replaced by noninvasive rejection surveillance with gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) testing. Demographics, outcomes of noninvasive surveillance score, hospital admissions, patient satisfaction, and health status on the medical outcomes study 12-item short-form health survey (SF-12) were collected and analyzed, using t tests and χ2 tests. Thematic qualitative analysis was performed for open-ended responses. Results: Among 90 patients, 31 (33%) were enrolled. A total of 36 combined GEP/dd-cfDNA tests were performed; 22 (61%) had negative results for both, 10 (27%) had positive GEP/negative dd-cfDNA results, 4 (11%) had negative GEP/positive dd-cfDNA results, and 0 were positive on both. All patients with a positive dd-cfDNA result (range: 0.19%-0.81%) underwent EMB with no significant cellular or antibody-mediated rejection. A total of 15 cases (42%) had immunosuppression reduction, and this increased to 55% in patients with negative concordant testing. Overall, patients' reported satisfaction was 90%, and on thematic analysis they were more satisfied, with less anxiety, during the noninvasive testing experience. Conclusions: Noninvasive rejection surveillance was associated with the ability to lower immunosuppression, increase satisfaction, and reduce anxiety in HT recipients, minimizing exposure for patients and providers during a global pandemic.

Contexte: La pandémie de COVID-19 a réduit l'accès à la biopsie endomyocardique pour surveiller le risque de rejet après une greffe du cœur. Cette étude est la première à être menée au Canada pour évaluer le rôle de la surveillance non invasive du risque de rejet en personnalisant le titrage de l'immunosuppression et la satisfaction du patient après la greffe cardiaque. Méthodologie: Dans le cadre de cette étude de cohorte prospective à méthodes mixtes, des adultes ayant reçu une greffe cardiaque depuis plus de six mois ont vu leurs biopsies endomyocardiques régulières remplacées par une surveillance non invasive du risque de rejet qui consiste à établir le profil de l'expression génique et à analyser l'ADN acellulaire dérivé du donneur. Les données démographiques, les résultats du score de surveillance non invasive, les admissions à l'hôpital, la satisfaction des patients et l'état de santé tirés du questionnaire SF-12 (questionnaire abrégé sur la santé comprenant 12 items) de l'étude sur les issues médicales ont été colligés et analysés au moyen des tests T et des tests χ2. Les réponses ouvertes ont fait l'objet d'une analyse qualitative thématique. Résultats: Parmi 90 patients, 31 (33 %) ont été recrutés. Au total, 36 tests combinés de profilages de l'expression génique et d'ADN acellulaire dérivé du donneur ont été réalisés; les résultats ont été négatifs pour les deux tests dans 22 cas (61 %), positifs pour le profilage de l'expression génique et négatifs pour l'ADN acellulaire dans 10 cas (27 %), négatifs pour le profilage de l'expression génique et positifs pour l'ADN acellulaire dans quatre cas (11 %) et aucun cas n'a donné de résultats positifs pour les deux types de tests. Tous les patients qui ont donné des résultats positifs à l'analyse de l'ADN acellulaire dérivé du donneur (fourchette : 0,19 % à 0,81 %) ont subi une biopsie endomyocardique n'ayant révélé aucun rejet cellulaire ou à médiation par anticorps important. Au total, 15 cas (42 %) affichaient une immunosuppression réduite, proportion qui a grimpé à 55 % chez les patients dont les tests de concordance ont donné des résultats négatifs. Dans l'ensemble, le niveau de satisfaction rapporté par les patients était de 90 % et, à l'analyse thématique, ils étaient plus satisfaits et moins anxieux pendant les tests non invasifs. Conclusions: La surveillance non invasive du risque de rejet a été associée à la capacité de diminuer l'immunosuppression, d'augmenter la satisfaction et de réduire l'anxiété chez les patients qui ont reçu une greffe cardiaque, en plus de réduire l'exposition des patients et du personnel médical dans le contexte d'une pandémie.

A Tale of 2 Aneurysms: Cardiogenic Shock Secondary to Vascular Behçet's Syndrome.

A patient with vascular Behçet's syndrome (BS), a subtype of BS with mainly venous/arterial manifestations, presented with a left main aneurysm/thrombus and cardiogenic shock. The clinical diagnosis of BS includes mucocutaneous, vascular, and neurologic criteria. It is important to consider vascular BS as a nonatherosclerotic cause of coronary aneurysms. (Level of Difficulty: Intermediate.).

Left Ventricular Assist Device Support for Fabry Cardiomyopathy: A Case Series.

Patients with restrictive cardiomyopathy due to Fabry disease are often deemed ineligible for left ventricular assist device (LVAD) support due to the risk of suction events with a small LV cavity. We describe the first case series of LVAD support for Fabry disease. LVAD therapy can improve survival, quality of life, and provide clinical stability to start enzyme replacement therapy. Precautions at the time of surgery include rapid treatment of fever to avoid Fabry crises, involvement of a multidisciplinary team, and early initiation of rehabilitation. We describe LVAD support for both bridging and destination therapy.

Les patients qui ont une cardiomyopathie restrictive due à la maladie de Fabry sont souvent considérés non admissibles aux dispositifs d'assistance ventriculaire gauche (DAVG) en raison du risque de succion lié à la petite cavité VG. Nous décrivons la première série de cas liée aux DAVG en présence de la maladie de Fabry. La thérapie par DAVG peut contribuer à l'amélioration de la survie, de la qualité de vie et offrir une stabilité clinique pour débuter l'enzymothérapie de substitution. Parmi les précautions à prendre au moment de l'intervention chirurgicale figurent le traitement rapide de la fièvre pour éviter les crises de Fabry, la participation de l'équipe multidisciplinaire et la mise en place précoce de la réadaptation. Nous décrivons l'utilisation du DAVG à titre de pont jusqu'à la transplantation et à titre de thérapie définitive.

Mortality in patients with cardiogenic shock supported with VA ECMO: A systematic review and meta-analysis evaluating the impact of etiology on 29,289 patients.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA ECMO) is associated with variable outcomes. In this meta-analysis, we evaluated the mortality after VA ECMO across multiple etiologies of cardiogenic shock (CS). METHODS: In June 2019, we performed a systematic search selecting observational studies with ≥10 adult patients reporting on short-term mortality (30-day or mortality at discharge) after initiation of VA ECMO by CS etiology published after 2009. We performed meta-analyses using random effect models and used metaregression to evaluate mortality across CS etiology. RESULTS: We included 306 studies (29,289 patients): 25 studies on after heart transplantation (HTx) (771 patients), 13 on myocarditis (906 patients), 33 on decompensated heart failure (HF) (3,567 patients), 64 on after cardiotomy shock (8,231 patients), 10 on pulmonary embolism (PE) (221 patients), 80 on acute myocardial infarction (AMI) (7,774 patients), and 113 on after cardiac arrest [CA] (7,814 patients). With moderate certainty on effect estimates, we observed significantly different mortality estimates for various etiologies (p < 0.001), which is not explained by differences in age and sex across studies: 35% (95% CI: 29-42) for after HTx, 40% (95% CI: 33-46) for myocarditis, 53% (95% CI: 46-59) for HF, 52% (95% CI: 38-66) for PE, 59% (95% CI: 56-63) for cardiotomy, 60% (95% CI: 57-64) for AMI, 64% (95% CI: 59-69) for post‒in-hospital CA, and 76% (95% CI: 69-82) for post-out‒of-hospital CA. Univariable metaregression showed that variation in mortality estimates within etiology group was partially explained by population age, proportion of females, left ventricle venting, and CA. CONCLUSIONS: Using an overall estimate of mortality for patients with CS requiring VA ECMO is inadequate given the differential outcomes by etiology. To further refine patient selection and management to improve outcomes, additional studies evaluating patient characteristics impacting outcomes by specific CS etiology are needed.

Low-Density Lipoprotein Cholesterol Level Trends and the Development of Cardiac Allograft Vasculopathy After Heart Transplantation.

BACKGROUND: Unlike the relationship with atherosclerotic coronary artery disease, that between low-density lipoprotein cholesterol (LDL-C) and cardiac allograft vasculopathy (CAV) is unclear. Our objectives were to characterize lipid profiles early after heart transplantation (HT) and evaluate the relationship between early LDL-C and the development of CAV. METHODS: We retrospectively reviewed consecutive adults who underwent HT at 2 centres during the time period 2010-2018. The primary outcome was the incidence of angiographic CAV. The relationship between LDL-C and CAV was assessed using Cox proportional hazards and logistic regression models adjusted a priori for clinically important covariates, including recipient and donor age, recipient sex, ischemic time, and pre-HT diabetes. RESULTS: A total of 386 patients followed for a median (range) of 4.4 (2.8-6.8) years were included. LDL-C at baseline (2.11 ± 0.86 mmol/L) and 1 year after HT (2.20 ± 0.88 mmol/L) was similar (P = 0.21), but it was lower at the end of follow-up (1.89 ± 0.74 mmol/L, P < 0.01). Of 309 patients who underwent angiography, 54% had CAV. The risk of CAV did not vary according to baseline, 1-year, or change from baseline to 1-year LDL-C. The odds of CAV at 1 year were equally likely across LDL-C values (adjusted odds ratio 1.00, 95% confidence interval: 0.61-1.63 for baseline, and adjusted odds ratio 1.25, 95% confidence interval: 0.74-2.10 for 1-year LDL-C). CONCLUSIONS: No association was identified between early LDL-C and the development of CAV. Our findings do not support targeting a specific LDL-C for patients who do not otherwise meet criteria for guideline-recommended LDL-C target levels. Randomized studies are warranted to determine if lipid-lowering to a specific LDL-C target level modifies the risk of CAV.

INTRODUCTION: Contrairement à la relation avec l'athérosclérose coronarienne, la relation entre les concentrations de cholestérol de lipoprotéines à faible densité (cholestérol LDL) et la vasculopathie d'allogreffe cardiaque (VAC) n'est pas claire. Nos objectifs étaient de caractériser les profils lipidiques rapidement après la transplantation cardiaque (TC) et d'évaluer la relation entre les concentrations initiales de cholestérol LDL et l'apparition de la VAC. MÉTHODES: Nous avons passé en revue de façon rétrospective les adultes consécutifs qui avaient subi une TC dans deux établissements durant la période 2010-2018. Le critère d'évaluation principal était la fréquence de la VAC à l'angiographie. Nous avons évalué la relation entre les concentrations de cholestérol LDL et la VAC à l'aide des modèles à risques proportionnels de Cox et de régression logistique ajustés a priori sur les covariables importantes sur le plan clinique, notamment l'âge du receveur et du donneur, le sexe du receveur, la durée de l'ischémie et le diabète pré-TC. RÉSULTATS: Nous avons inclus un total de 386 patients suivis durant une médiane (étendue) de 4,4 (2,8-6,8) ans. Les concentrations initiales de cholestérol LDL (2,11 ± 0,86 mmol/l) et après 1 an (2,20 ± 0,88 mmol/l) étaient similaires (P = 0,21), mais elles étaient plus faibles à la fin du suivi (1,89 ± 0,74 mmol/l, P < 0,01). Parmi les 309 patients qui avaient subi une angiographie, 54 % avaient une VAC. Le risque de VAC ne variait pas en fonction des concentrations de cholestérol LDL du début, après un an, ou ne changeait pas entre le début et après un an. Les cotes de la VAC après 1 an étaient équiprobables dans toutes les valeurs de cholestérol LDL (rapport de cotes ajusté 1,00, intervalle de confiance [IC] à 95 % : 0,61-1,63 au début, et rapport de cotes ajusté 1,25, IC à 95 % : 0,74-2,10 pour les concentrations de cholestérol LDL après un an). CONCLUSIONS: Aucune association n'a été établie entre les concentrations initiales de cholestérol LDL et l'apparition de la VAC. Nos résultats n'étayent pas le ciblage de concentrations particulières de cholestérol LDL chez les patients qui ne satisfaisaient par ailleurs pas aux critères des concentrations cibles de cholestérol LDL recommandées par les lignes directrices. Des études à répartition aléatoire sont justifiées pour déterminer si la diminution des lipides à des concentrations cibles particulières de cholestérol LDL modifie le risque de VAC.

The effect of antiplatelet therapy on survival and cardiac allograft vasculopathy following heart transplantation: A systematic review and meta-analysis.

Cardiac allograft vasculopathy (CAV) is mediated by endothelial inflammation, platelet activation and thrombosis. Antiplatelet therapy may prevent the development of CAV. This systematic review and meta-analysis summarizes and appraises the evidence on the effect of antiplatelet therapy after heart transplantation (HT). CENTRAL(Ovid), MEDLINE(Ovid), Embase(Ovid) were searched from inception until April 30, 2020. Outcomes included CAV, all-cause mortality, and CAV-related mortality. Data were pooled using random-effects models. Seven observational studies including 2023 patients, mean age 52 years, 22% female, 47% with ischemic cardiomyopathy followed over a mean 7.1 years proved eligible. All studies compared acetylsalicylic acid (ASA) to no treatment and were at serious risk of bias. Data from 1911 patients in 6 studies were pooled in the meta-analyses. The evidence is very uncertain about the effect of ASA on all-cause or CAV-related mortality. ASA may reduce the development of CAV (RR 0.75, 95% CI: 0.44-1.29) based on very low certainty evidence. Two studies that conducted propensity-weighted analyses showed further reduction in CAV with ASA (HR 0.31, 95% CI: 0.13-0.74). In conclusion, there is limited evidence that ASA may reduce the development of CAV. Definitive resolution of the impact of antiplatelet therapy on CAV and mortality will require randomized clinical trials.

The Effect of Age on Outcomes After Destination-Therapy Left Ventricular Assist Device Implantation: An Analysis of the IMACS Registry.

BACKGROUND: As patients with advanced heart failure are living longer, defining the impact of left ventricular assist devices (LVADs) on outcomes in an aging population is of great importance. We describe overall survival, rates of adverse events (AEs), and post-AE survival in patients age ≥ 70 years vs age 50-69 years after destination-therapy (DT) LVAD implantation. METHODS: A retrospective analysis was conducted with the use of the International Society for Heart and Lung Transplantation Mechanically Assisted Circulatory Support (IMACS) registry. All adults age ≥ 50 years with a continuous-flow DT LVAD from 2013 to 2017 were included. The primary outcome was all-cause mortality. The secondary outcomes were the incidence of and survival after gastrointestinal (GI) bleeding, infection, stroke, pump thrombosis, pump exchange, and right-side heart failure. Mortality and AEs were assessed with the use of competing risk models. RESULTS: At total of 5,572 patients were included: 3,700 aged 50-69 and 1,872 aged ≥ 70. All-cause mortality by 42 months was 55.8% in patients aged ≥ 70 and 44.8% in patients aged 50-69 (P = 0.001). Patients aged ≥ 70 had a 37.8% higher risk of death after DT LVAD implantation (hazard ratio 1.378, 95% CI 1.251-1.517). Patients aged ≥ 70 had higher risk of GI bleeding but lower risk of right-side heart failure. There was no difference between age groups for risk of infection or stroke. Experiencing any AE was associated with an increased risk of death that did not vary with age. CONCLUSIONS: Patients aged ≥ 70 years have reduced survival after DT LVAD, in part because of increased GI bleeding, while the incidence of other AEs is similar to that of patients aged 50-69 years. Careful patient selection beyond age alone may allow for optimal outcomes after DT LVAD implantation.

Risk prediction models for survival after heart transplantation: A systematic review.

Risk prediction scores have been developed to predict survival following heart transplantation (HT). Our objective was to systematically review the model characteristics and performance for all available scores that predict survival after HT. Ovid Medline and Epub Ahead of Print and In-Process & Other Non-Indexed Citations, Ovid Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Clinical Trials were searched to December 2018. Eligible articles reported a score to predict mortality following HT. Of the 5392 studies screened, 21 studies were included that derived and/or validated 16 scores. Seven (44%) scores were validated in external cohorts and 8 (50%) assessed model performance. Overall model discrimination ranged from poor to moderate (C-statistic/area under the receiver operating characteristics 0.54-0.77). The IMPACT score was the most widely validated, was well calibrated in two large registries, and was best at discriminating 3-month survival (C-statistic 0.76). Most scores did not perform particularly well in any cohort in which they were assessed. This review shows that there are insufficient data to recommend the use of one model over the others for prediction of post-HT outcomes.