Shortcut learning in medical AI hinders generalization: method for estimating AI model generalization without external data.

Healthcare datasets are becoming larger and more complex, necessitating the development of accurate and generalizable AI models for medical applications. Unstructured datasets, including medical imaging, electrocardiograms, and natural language data, are gaining attention with advancements in deep convolutional neural networks and large language models. However, estimating the generalizability of these models to new healthcare settings without extensive validation on external data remains challenging. In experiments across 13 datasets including X-rays, CTs, ECGs, clinical discharge summaries, and lung auscultation data, our results demonstrate that model performance is frequently overestimated by up to 20% on average due to shortcut learning of hidden data acquisition biases (DAB). Shortcut learning refers to a phenomenon in which an AI model learns to solve a task based on spurious correlations present in the data as opposed to features directly related to the task itself. We propose an open source, bias-corrected external accuracy estimate, PEst, that better estimates external accuracy to within 4% on average by measuring and calibrating for DAB-induced shortcut learning.

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.

HLA sensitization is associated with an increased risk of primary graft dysfunction after heart transplantation.

Primary graft dysfunction (PGD) is a leading cause of early morbidity and mortality following heart transplantation (HT). We sought to determine the association between pretransplant human leukocyte antigen (HLA) sensitization, as measured using the calculated panel reactive antibody (cPRA) value, and the risk of PGD. METHODS: Consecutive adult HT recipients (n = 596) from 1/2015 to 12/2019 at 2 US centers were included. Severity of PGD was based on the 2014 International Society for Heart and Lung Transplantation consensus statement. For each recipient, unacceptable HLA antigens were obtained and locus-specific cPRA (cPRA-LS) and pre-HT donor-specific antibodies (DSA) were assessed. RESULTS: Univariable logistic modeling showed that peak cPRA-LS for all loci and HLA-A was associated with increased severity of PGD as an ordinal variable (all loci: OR 1.78, 95% CI: 1.01-1.14, p = 0.025, HLA-A: OR 1.14, 95% CI: 1.03-1.26, p = 0.011). Multivariable analysis showed peak cPRA-LS for HLA-A, recipient beta-blocker use, total ischemic time, donor age, prior cardiac surgery, and United Network for Organ Sharing status 1 or 2 were associated with increased severity of PGD. The presence of DSA to HLA-B was associated with trend toward increased risk of mild-to-moderate PGD (OR 2.56, 95% CI: 0.99-6.63, p = 0.053), but DSA to other HLA loci was not associated with PGD. CONCLUSIONS: Sensitization for all HLA loci, and specifically HLA-A, is associated with an increased severity of PGD. These factors should be included in pre-HT risk stratification to minimize the risk of PGD.

Combined FDG PET/MRI versus Standard-of-Care Imaging in the Evaluation of Cardiac Sarcoidosis.

Purpose: To compare combined cardiac fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/MRI with standard-of-care evaluation using cardiac MRI, 18F-FDG PET/CT, and SPECT perfusion imaging in suspected cardiac sarcoidosis (CS) with respect to radiation dose, imaging duration, and diagnostic test performance. Materials and Methods: Consecutive patients with suspected CS undergoing clinical evaluation with cardiac 18F-FDG PET/CT and gated rest technetium 99m sestamibi SPECT perfusion imaging were prospectively recruited between November 2017 and May 2021 for parallel assessment with combined cardiac 18F-FDG PET/MRI on the same day (ClinicalTrials.gov identifier, NCT03356756). Total effective radiation dose and imaging duration were compared between approaches (combined cardiac PET/MRI vs separate cardiac MRI, PET/CT, and SPECT). MRI findings were initially interpreted without PET data, and then PET and late gadolinium enhancement images were fused and interpreted together. Final diagnosis of CS was established using Japanese Ministry of Health and Welfare guidelines. Results: Forty participants (mean age, 54 years ± 14 [SD]; 26 [65%] male participants) were included, 14 (35%) with a final diagnosis of CS. Compared with separate cardiac MRI, PET/CT, and SPECT perfusion imaging, combined cardiac PET/MRI had 52% lower total radiation dose (8.0 mSv ± 1.2 vs 16.8 mSv ± 1.6, P < .001) and 43% lower total imaging duration (122 minutes ± 15 vs 214 minutes ± 26, P < .001). Combined PET/MRI had the highest area under the curve for diagnosis of CS (0.84) with 96% specificity and 71% sensitivity for colocalized FDG uptake and late gadolinium enhancement in a pattern typical for CS. Conclusion: In the evaluation of suspected CS, combined cardiac 18F-FDG PET/MRI had a lower radiation dose, shorter imaging duration, and higher diagnostic performance compared with standard-of-care imaging.Clinical trial registration no. NCT03356756Keywords: Cardiac Sarcoidosis, 18F-FDG PET/MRI, 18F-FDG PET/CT, SPECT Perfusion Imaging, Cardiac MRI, Standard-of-Care Imaging Supplemental material is available for this article. © RSNA, 2023.

Tricuspid regurgitation, right ventricular function, and renal congestion: a cardiorenal triangle.

There is a growing interest in the evaluation of tricuspid regurgitation due to its increasing prevalence and detrimental impact on clinical outcomes. Historically, it has been coined the "forgotten" defect in the field of valvular heart disease due to the lack of effective treatments to improve prognosis. However, the development of percutaneous treatment techniques has led to a new era in its management, with promising results and diminished complication risk. In spite of these advances, a comprehensive exploration of the pathophysiological mechanisms is essential to establish clear indications and optimal timing for medical and percutaneous intervention. This review will address the most important aspects related to the diagnosis, pathophysiology and treatment of tricuspid regurgitation from a cardiorenal perspective, with a special emphasis on the interaction between right ventricular dysfunction and the development of hepatorenal congestion.

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.

Rethinking Donor and Recipient Risk Matching in Europe and North America: Using Heart Transplant Predictors of Donor and Recipient Risk.

BACKGROUND: In Europe, there is greater acceptance of hearts from higher-risk donors for transplantation, whereas in North America, the donor heart discard rate is significantly higher. A Donor Utilization Score (DUS) was used to compare European and North American donor characteristics for recipients included in the International Society for Heart and Lung Transplantation registry from 2000 to 2018. DUS was further evaluated as an independent predictor for 1-year freedom from graft failure, after adjusting for recipient risk. Lastly, we assessed donor-recipient risk matching with the outcome of 1-year graft failure. METHODS: DUS was applied to the International Society for Heart and Lung Transplantation cohort using meta-modeling. Posttransplant freedom from graft failure was summarized by Kaplan-Meier survival. Multivariable Cox proportional hazard regression was applied to quantify the effects of DUS and Index for Mortality Prediction After Cardiac Transplantation score on the 1-year risk of graft failure. We present 4 donor/recipient risk groups using the Kaplan-Meier method. RESULTS: European centers accept significantly higher-risk donor hearts compared to North America. DUS 0.45 versus 0.54, P<0.005). DUS was an independent predictor for graft failure with an inverse linear relationship when adjusted for covariates (P<0.001). The Index for Mortality Prediction After Cardiac Transplantation score, a validated tool to assess recipient risk, was also independently associated with 1-year graft failure (P<0.001). In North America, 1-year graft failure was significantly associated with donor-recipient risk matching (log-rank P<0.001). One-year graft failure was highest with pairing of high-risk recipients and donors (13.1% [95% CI, 10.7%-13.9%]) and lowest among low-risk recipients and donors (7.4% [95% CI, 6.8%-8.0%]). Matching of low-risk recipients with high-risk donors was associated with significantly less graft failure (9.0% [95% CI, 8.3%-9.7%]) than high-risk recipients with low-risk donors (11.4% [95% CI, 10.7%-12.2%]) Conclusions: European heart transplantation centers are more likely to accept higher-risk donor hearts than North American centers. Acceptance of borderline-quality donor hearts for lower-risk recipients could improve donor heart utilization without compromising recipient survival.

Primary Graft Dysfunction Is Associated With Development of Early Cardiac Allograft Vasculopathy, but Not Other Immune-mediated Complications, After Heart Transplantation.

BACKGROUND: We investigated associations between primary graft dysfunction (PGD) and development of acute cellular rejection (ACR), de novo donor-specific antibodies (DSAs), and cardiac allograft vasculopathy (CAV) after heart transplantation (HT). METHODS: A total of 381 consecutive adult HT patients from January 2015 to July 2020 at a single center were retrospectively analyzed. The primary outcome was incidence of treated ACR (International Society for Heart and Lung Transplantation grade 2R or 3R) and de novo DSA (mean fluorescence intensity >500) within 1 y post-HT. Secondary outcomes included median gene expression profiling score and donor-derived cell-free DNA level within 1 y and incidence of cardiac allograft vasculopathy (CAV) within 3 y post-HT. RESULTS: When adjusted for death as a competing risk, the estimated cumulative incidence of ACR (PGD 0.13 versus no PGD 0.21; P = 0.28), median gene expression profiling score (30 [interquartile range, 25-32] versus 30 [interquartile range, 25-33]; P = 0.34), and median donor-derived cell-free DNA levels was similar in patients with and without PGD. After adjusting for death as a competing risk, estimated cumulative incidence of de novo DSA within 1 y post-HT in patients with PGD was similar to those without PGD (0.29 versus 0.26; P = 0.10) with a similar DSA profile based on HLA loci. There was increased incidence of CAV in patients with PGD compared with patients without PGD (52.6% versus 24.8%; P = 0.01) within the first 3 y post-HT. CONCLUSIONS: During the first year after HT, patients with PGD had a similar incidence of ACR and development of de novo DSA, but a higher incidence of CAV when compared with patients without PGD.

Prognostic Value of Cardiac MRI and FDG PET in Cardiac Sarcoidosis: A Systematic Review and Meta-Analysis.

Background There is no consensus regarding the relative prognostic value of cardiac MRI and fluorodeoxyglucose (FDG) PET in cardiac sarcoidosis. Purpose To perform a systematic review and meta-analysis of the prognostic value of cardiac MRI and FDG PET for major adverse cardiac events (MACE) in cardiac sarcoidosis. Materials and Methods In this systematic review, MEDLINE, Ovid Epub, CENTRAL, Embase, Emcare, and Scopus were searched from inception until January 2022. Studies that evaluated the prognostic value of cardiac MRI or FDG PET in adults with cardiac sarcoidosis were included. The primary outcome of MACE was assessed as a composite including death, ventricular arrhythmia, and heart failure hospitalization. Summary metrics were obtained using random-effects meta-analysis. Meta-regression was used to assess covariates. Risk of bias was assessed using the Quality in Prognostic Studies, or QUIPS, tool. Results Thirty-seven studies were included (3489 patients with mean follow-up of 3.1 years ± 1.5 [SD]); 29 studies evaluated MRI (2931 patients) and 17 evaluated FDG PET (1243 patients). Five studies directly compared MRI and PET in the same patients (276 patients). Left ventricular late gadolinium enhancement (LGE) at MRI and FDG uptake at PET were both predictive of MACE (odds ratio [OR], 8.0 [95% CI: 4.3, 15.0] [P < .001] and 2.1 [95% CI: 1.4, 3.2] [P < .001], respectively). At meta-regression, results varied by modality (P = .006). LGE (OR, 10.4 [95% CI: 3.5, 30.5]; P < .001) was also predictive of MACE when restricted to studies with direct comparison, whereas FDG uptake (OR, 1.9 [95% CI: 0.82, 4.4]; P = .13) was not. Right ventricular LGE and FDG uptake were also associated with MACE (OR, 13.1 [95% CI: 5.2, 33] [P < .001] and 4.1 [95% CI: 1.9, 8.9] [P < .001], respectively). Thirty-two studies were at risk for bias. Conclusion Left and right ventricular late gadolinium enhancement at cardiac MRI and fluorodeoxyglucose uptake at PET were predictive of major adverse cardiac events in cardiac sarcoidosis. Limitations include few studies with direct comparison and risk of bias. Systematic review registration no. CRD42021214776 (PROSPERO) © RSNA, 2023 Supplemental material is available for this article.

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.

Combining donor derived cell free DNA and gene expression profiling for non-invasive surveillance after heart transplantation.

BACKGROUND: Donor-derived cell free DNA (dd-cfDNA) and gene expression profiling (GEP) offer noninvasive alternatives to rejection surveillance after heart transplantation; however, there is little evidence on the paired use of GEP and dd-cfDNA for rejection surveillance. METHODS: A single center, retrospective analysis of adult heart transplant recipients. A GEP cohort, transplanted from January 1, 2015 through December 31, 2017 and eligible for rejection surveillance with GEP was compared to a paired testing cohort, transplanted July 1, 2018 through June 30, 2020, with surveillance from both dd-cfDNA and GEP. The primary outcomes were survival and rejection-free survival at 1 year post-transplant. RESULTS: In total 159 patients were included, 95 in the GEP and 64 in the paired testing group. There were no differences in baseline characteristics, except for less use of induction in the paired testing group (65.6%) compared to the GEP group (98.9%), P < .01. At 1-year, there were no differences between the paired testing and GEP groups in survival (98.4% vs. 94.7%, P = .23) or rejection-free survival (81.3% vs. 73.7% P = .28). CONCLUSIONS: Compared to post-transplant rejection surveillance with GEP alone, pairing dd-cfDNA and GEP testing was associated with similar survival and rejection-free survival at 1 year while requiring significantly fewer biopsies.

Cardiac MRI and Clinical Outcomes in TMEM43 Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy is an inherited cardiomyopathy that can involve both ventricles. Several genes have been identified as pathogenic in arrhythmogenic cardiomyopathy, including TMEM43. However, there are limited data on cardiac MRI findings in patients with TMEM43 variants to date. In this case series, cardiac MRI findings and clinical outcomes are described in 14 patients with TMEM43 variants, including eight (57%) with the pathogenic p.Ser358Leu variant (six female patients; mean age, 33 years ± 15 [SD]) and six (43%) with a TMEM43 variant of unknown significance (three female patients; mean age, 38 years ± 11). MRI findings demonstrated left ventricular systolic dysfunction in eight (57%) patients and right ventricular dysfunction in four (29%) patients. Among the nine patients with late gadolinium enhancement imaging, left ventricular late gadolinium enhancement was present in seven (78%; all subepicardial) patients. In summary, TMEM43 variants are associated with high prevalence of subepicardial late gadolinium enhancement and left ventricular dysfunction. Keywords: Arrhythmogenic Cardiomyopathy, Arrhythmogenic Right Ventricular Cardiomyopathy, TMEM43, Cardiac MRI, Genetic Variants Supplemental material is available for this article.

Getting ahead of the game: in-hospital initiation of HFrEF therapies.

Hospitalizations for heart failure (HF) have become a global problem worldwide. Each episode of HF decompensation may lead to deleterious short- and long- term consequences, but on the other hand is an unique opportunity to adjust the heart failure pharmacotherapy. Thus, in-hospital and an early post-discharge period comprise an optimal timing for initiation and optimization of the comprehensive management of HF. This timeframe affords clinicians an opportunity to up titrate and adjust guideline-directed medical therapies (GDMT) to potentially mitigate poor outcomes associated post-discharge and longer-term. This review will cover this timely concept, present the data of utilization of GDMT in HF populations, discuss recent evidence for in-hospital initiation and up-titration of GDMT with a need for post-discharge follow-up and implementation this into clinical practice in patients with heart failure and reduced ejection fraction.

Diagnostic Accuracy of Cardiac MRI versus FDG PET for Cardiac Sarcoidosis: A Systematic Review and Meta-Analysis.

Background There is limited consensus regarding the relative diagnostic performance of cardiac MRI and fluorodeoxyglucose (FDG) PET for cardiac sarcoidosis. Purpose To perform a systematic review and meta-analysis to compare the diagnostic accuracy of cardiac MRI and FDG PET for cardiac sarcoidosis. Materials and Methods Medline, Ovid Epub, Cochrane Central Register of Controlled Trials, Embase, Emcare, and Scopus were searched from inception until January 2022. Inclusion criteria included studies that evaluated the diagnostic accuracy of cardiac MRI or FDG PET for cardiac sarcoidosis in adults. Data were independently extracted by two investigators. Summary accuracy metrics were obtained by using bivariate random-effects meta-analysis. Meta-regression was used to assess the effect of different covariates. Risk of bias was assessed using the Quality Assessment Tool for Diagnostic Accuracy Studies-2 tool. The study protocol was registered a priori in the International Prospective Register of Systematic Reviews (Prospero protocol CRD42021214776). Results Thirty-three studies were included (1997 patients, 687 with cardiac sarcoidosis); 17 studies evaluated cardiac MRI (1031 patients) and 26 evaluated FDG PET (1363 patients). Six studies directly compared cardiac MRI and PET in the same patients (303 patients). Cardiac MRI had higher sensitivity than FDG PET (95% vs 84%; P = .002), with no difference in specificity (85% vs 82%; P = .85). In a sensitivity analysis restricted to studies with direct comparison, point estimates were similar to those from the overall analysis: cardiac MRI and FDG PET had sensitivities of 92% and 81% and specificities of 72% and 82%, respectively. Covariate analysis demonstrated that sensitivity for FDG PET was highest with quantitative versus qualitative evaluation (93% vs 76%; P = .01), whereas sensitivity for MRI was highest with inclusion of T2 imaging (99% vs 88%; P = .001). Thirty studies were at risk of bias. Conclusion Cardiac MRI had higher sensitivity than fluorodeoxyglucose PET for diagnosis of cardiac sarcoidosis but similar specificity. Limitations, including risk of bias and few studies with direct comparison, necessitate additional study. © RSNA, 2022 Online supplemental material is available for this article.

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.

Management of Frail and Older Homebound Patients With Heart Failure: A Contemporary Virtual Ambulatory Model.

BACKGROUND: Heart failure (HF) affects many patients who are older and frail, presenting multiple physical barriers to accessing specialty care in a traditional ambulatory clinic model. Here, we present an assisted virtual care model in which a home visiting nurse facilitated video visits with a HF cardiologist to follow homebound, frail, and older patients with HF. METHODS: This is a pragmatic, quasi-experimental, pre-post, single-centre study. It included homebound, frail, and older patients with HF from 2015 to 2019 who were followed for 1 year; in-person clinic visits were completely replaced by nurse-facilitated virtual video visits. Outcomes evaluated included annualized hospitalization rate, number of hospitalization days, and number of emergency department visits. RESULTS: A total of 49 patients were included, with a median age of 86 (83-93) years, and were followed for 1 year after enrollment. Among patients enrolled, HF with preserved ejection fraction was the most common subtype (57%). Compared to the year prior to enrollment, patients had a lower mortality-adjusted all-cause annualized hospitalization rate in the year following enrollment (2.57 vs 1.78, P < 0.0001). Compared to the year prior, the number of mortality-adjusted all-cause hospitalization days was significantly lower in the year following enrollment (27.2 vs 21.4, P < 0.0001). There was a reduction in the number of all-cause annualized emergency department visits (3.10 vs 2.27, P = 0.003). CONCLUSIONS: Nurse-assisted virtual visits may be a preferable strategy for homebound, frail, and older patients with HF to receive longitudinal care. This approach may represent a plausible strategy to care for other patients with significant barriers to accessing specialized cardiac care.

CONTEXTE: L'insuffisance cardiaque (IC) touche de nombreux patients âgés et fragiles, et dresse maints obstacles physiques à l'accès aux soins spécialisés au sein d'un modèle classique de soins cliniques ambulatoires. Dans le présent article, nous exposons un modèle de soins virtuels assistés où une infirmière visiteuse assure par vidéoconsultation, avec un cardiologue, le suivi de patients âgés et fragiles atteints d'IC confinés à la maison. MÉTHODOLOGIE: Une étude monocentrique et pragmatique, quasi expérimentale de type « avant-après ¼, a été menée de 2015 à 2019 auprès de patients âgés et fragiles atteints d'IC confinés à la maison. Les patients ont été suivis durant un an; les consultations en personne ont été entièrement remplacées par des vidéoconsultations effectuées par une infirmière. Les paramètres évalués comprenaient le taux annualisé d'hospitalisation, le nombre de jours d'hospitalisation et le nombre de consultations aux urgences. RÉSULTATS: Au total, 49 patients dont l'âge médian était de 86 ans (83-93 ans) ont été suivis durant un an à compter de leur admission à l'étude. L'IC à fraction d'éjection préservée était le sous-type d'IC le plus fréquent (57 %) chez les patients participant à l'étude. Par comparaison à l'année précédente, le taux annualisé d'hospitalisation toutes causes confondues ajusté en fonction de la mortalité a été plus faible chez les patients au cours de l'année où ils ont été suivis dans le cadre de l'étude (2,57 vs 1,78, P < 0,0001). Toujours par comparaison à l'année précédente, le nombre de jours d'hospitalisation toutes causes confondues ajusté en fonction de la mortalité a été significativement inférieur chez les patients au cours de l'année où ils ont été suivis dans le cadre de l'étude (27,2 vs 21,4, P < 0,0001). Le nombre annualisé de consultations aux urgences toutes causes confondues a quant à lui diminué (3,10 vs 2,27, P = 0,003). CONCLUSIONS: Les consultations virtuelles assistées par une infirmière peuvent constituer une stratégie à privilégier dans la prestation de soins longitudinaux à des patients âgés et fragiles atteints d'IC qui sont confinés à la maison. Cette approche pourrait représenter une stratégie plausible pour prodiguer des soins à d'autres patients qui sont confrontés à d'importants obstacles limitant leur accès à des soins spécialisés en cardiologie.

Impact of using higher-risk donor hearts for candidates with pre-transplant mechanical circulatory support.

BACKGROUND: We evaluated post-heart transplant (HTx) outcomes after use of higher-risk donor hearts for candidates supported with pre-HTx mechanical circulatory support (MCS). METHODS: In this retrospective analysis of the national United Network for Organ Sharing registry, a total of 9,915 adult candidates on MCS underwent HTx from January 1, 2010 to March 31, 2019. Multi-organ, re-transplant, and congenital heart disease patients were excluded. Higher-risk donor organs met at least one of the following criteria: left ventricular ejection fraction <50%, donor to recipient predicted heart mass ratio <0.86, donor age >55 years, or ischemic time >4 hours. Primary outcome was 1 year post-transplant survival. RESULTS: Among HTx recipients, 3688 (37.2%) received higher-risk donor hearts. Candidates supported with pre-HTx extracorporeal membrane oxygenation or biventricular assist device (n = 374, 3.8%) who received higher-risk donor hearts had comparable 1 year survival (HR: 1.14, 95% CI: [0.67-1.93], p = 0.64) to recipients of standard-risk donor hearts, when adjusted for recipient age and sex. In candidates supported with intra-aortic balloon pump (n = 1391, 14.6%), transplantation of higher-risk donor hearts did not adversely affect 1 year survival (HR: 0.80, 95% CI: [0.52-1.22], p = 0.30). Patients on durable left ventricular assist devices (LVAD) who received higher-risk donor hearts had comparable 1 year survival to continued LVAD support on the waitlist, but mortality was increased compared to those who received standard-risk donor hearts (HR: 1.37, 95% CI: [1.11-1.70], p = 0.004). CONCLUSIONS: Patients requiring pre-HTx temporary MCS who received higher-risk donor hearts had comparable 1 year post-transplant survival to those who received standard-risk donor hearts. Stable patients on durable LVADs may benefit from waiting for standard-risk donor hearts.