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.

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.

Physician Judgement vs Model-Predicted Prognosis in Patients With Heart Failure.

BACKGROUND: Previous evidence suggests that cardiologists and family doctors have limited accuracy in predicting patient prognosis. Predictive models with satisfactory accuracy for estimating mortality in patients with heart failure (HF) exist; physicians, however, seldom use these models. We evaluated the relative accuracy of physician vs model prediction to estimate 1-year survival in ambulatory patients with HF. METHODS: We conducted a single-centre cross-sectional study involving 150 consecutive ambulatory patients with HF >18 years of age with a left ventricular ejection fraction ≤40%. Each patient's cardiologist and family doctor provided their predicted 1-year survival, and predicted survival scores were calculated using 3 models: HF Meta-Score, Seattle Heart Failure Model (SHFM), and Meta-Analysis Global Group in Chronic HF (MAGGIC) score. We compared accuracy between physician and model predictions using intraclass correlation (ICC). RESULTS: Median predicted survival by HF cardiologists was lower (median 80%, interquartile range [IQR]: 61%-90%) than that predicted by family physicians (median 90%, IQR 70%-99%, P = 0.08). One-year median survival calculated by the HF Meta-Score (94.6%), SHFM (95.4%), and MAGGIC (88.9%,) proved as high or higher than physician estimates. Agreement among HF cardiologists (ICC 0.28-0.41) and family physicians (ICC 0.43-0.47) when compared with 1-year model-predicted survival scores proved limited, whereas the 3 models agreed well (ICC > 0.65). CONCLUSIONS: HF cardiologists underestimated survival in comparison with family physicians, whereas both physician estimates were lower than calculated model estimates. Our results provide additional evidence of potential inaccuracy of physician survival predictions in ambulatory patients with HF. These results should be validated in longitudinal studies collecting actual survival.

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.

Clustered Emergency Room Visits Following an Acute Heart Failure Admission: A Population-Based Study.

BACKGROUND: While it is well known that heart failure patients presenting to the emergency room (ER) have high short-term mortality after discharge, the outcomes of patients with heart failure with repeated ER visits within a short time are not known. In this study, we aimed to determine whether clustering is associated with an increased risk of death. METHODS AND RESULTS: This is a retrospective, population-based cohort study with an accrual window between 2003 and 2014 and maximal follow-up up to and including March 31, 2015. Data were obtained from administrative databases from Ontario, Canada. Clustering was defined a priori as 3 or more ER visits within a 6-month period. The main outcome of interest was time to death conditional on 6-month survival. A total of 72 810 patients with an index hospitalization for acute heart failure were evaluated. ER clustering was observed in 15.1% of the population. Increased burden of comorbidities, primary rural residence, and lack of primary care provider were identified as factors associated with ER clustering. Age- and sex-adjusted mortality for clustered patients was higher than for nonclustered (hazard ratio [HR] 1.51; 95% confidence interval, 1.47-1.55, P<0.0001). Adjusted mortality risk was also higher for patients with clustered ER visits (HR 1.42; 95% confidence interval 1.38-1.46; P<0.0001). CONCLUSIONS: Clustering, as defined by 3 or more ER visits for any reason within 6 months of index heart failure hospitalization reflects a novel risk factor associated with increased mortality. Future research into the strategies to better manage complex patients with heart failure with recurrent ER visits are warranted.

Avoiding Clinical Errors With Bedside Echocardiography: A Randomized Clinical Study.

Clinicians have strong opinions about whether they should be provided the clinical history before or after bedside testing. We hypothesized that diagnostic accuracy is improved when a concordant clinical history is provided before a diagnostic test. To investigate whether the timing (before or after) and the consistency (concordant vs discordant) of the clinical history in the setting of focused bedside echocardiography affects clinician diagnostic accuracy and management decisions. Thirty-two cardiology residents were asked to perform a bedside echocardiogram on a Vimedix 3D mannequin. Half of the histories were provided before echocardiography and half after echocardiography. Half were consistent with the echocardiographic diagnosis (concordant), and half were suggestive of a plausible alternative diagnosis (discordant). Participants were asked for a diagnosis and management plan. The primary outcome was the diagnostic accuracy of the echocardiographic images. The secondary outcome was the management plan. Overall diagnostic accuracy was 63%. If the clinical history was provided before the bedside testing, it significantly improved diagnostic accuracy if it was concordant and it diminished accuracy if it was discordant (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.16-0.80; P = 0.001). Clinical history, whether concordant or discordant, had no significant impact if provided after the images were obtained. Appropriate management was chosen 77% of the time and was chosen less often with discordant compared with concordant histories (OR, 0.25; 95% CI, 0.11-0.57; P = 0.001). Our study suggests a significant downside to clinical information received before echocardiography when the information is discordant, raising the possibility that receiving clinical information after echocardiography may be superior for diagnostic accuracy.

The prognostic significance of frailty compared to peak oxygen consumption and B-type natriuretic peptide in patients with advanced heart failure.

Frailty assessment has become an integral part of the evaluation of potential candidates for heart transplantation and ventricular assist device (HTx/VAD). The impact of frailty, as a heart failure risk factor or to identify those who will derive the greatest benefit with HTx/VAD remains unclear. The aim of this study was to evaluate the independent prognostic relevance of frailty assessment from peak oxygen consumption (peak VO2 ) or B-type natriuretic peptide (BNP) on mortality in patients referred for advanced heart failure therapies. Frailty was measured using modified Fried frailty criteria. In 201 consecutive patients, during a median follow-up of 17.5 months (IQR 11-29.2), there were 25 (12.4%) deaths. One-year survival was 100%, 94%, and 78% in nonfrail, prefrail, and frail patients, respectively (log rank P = .0001). Frailty was associated with a twofold increase risk of death (HR 2.01, P < .0001, 95% CI 1.42-2.84). When adjusted for BNP or peak VO2 , frailty was not associated with a significant risk of all-cause death. However, when peak VO2 is stratified into two categories (≥12 mL/kg/min vs <12 mL/kg/min), frailty was associated with increased mortality in patients with a lower peak VO2 (HR 1.72, P = .006).

Early pneumopericardium after heart transplantation.

A 60-year-old woman with a history of dilated cardiomyopathy underwent heart transplantation. One month post discharge, she presented to clinic with low-grade fever and productive cough. Her chest radiograph showed air-fluid levels in the pericardial silhouette. Transthoracic echocardiogram showed a large complex pericardial collection with no evidence of cardiac tamponade. The patient was urgently taken to the operating room for exploration. A large "egg-shaped" mass in the pericardium measuring 10 × 12 cm with gaseous material was aspirated. As the posterior wall of the mass was firmly adhered to the right atrium, the capsule was incompletely excised. We present the case of a potentially life-threatening complication post transplantation that required surgical debridement and life-long antibiotic suppressive therapy. To our knowledge, this is the first report of purulent pericardial collection caused by Enterobacter cancerogenous. Further research is required to better understand the biology of this microorganism and the role it may play as a pathogen in immunocompromised patients following solid organ transplantation.