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Background: Diaphragm atrophy can contribute to dyspnea in patients with heart failure (HF) with its link to central neurohormonal overactivation. HF medications that cross the blood-brain barrier could act centrally and improve respiratory function, potentially alleviating diaphragmatic atrophy. Therefore, we compared the benefit of central- vs peripheral-acting HF drugs on respiratory function, as assessed by a single cardiopulmonary exercise test (CPET) and outcomes in HF patients. Methods: A retrospective study was conducted of 624 ambulatory adult HF patients (80% male) with reduced left ventricular ejection fraction ≤ 40% and a complete CPET, followed at a single institution between 2001 and 2017. CPET parameters, and the outcomes all-cause death, a composite endpoint (all-cause death, need for left ventricular assist device, heart transplantation), and all-cause and/or HF hospitalizations, were compared in patients receiving central-acting (n = 550) vs peripheral-acting (n = 74) drugs. Results: Compared to patients who receive peripheral-acting drugs, patients who receive central-acting drugs had better respiratory function (peak breath-by breath oxygen uptake [VO2], P = 0.020; forced expiratory volume in 1 second [FEV1], P = 0.007), and ventilatory efficiency (minute ventilation / carbon dioxide production [VE/VCO2], P < 0.001; end-tidal carbon dioxide tension [PETCO2], P = 0.015; and trend for forced vital capacity [FVC], P = 0.056). Many of the associations between the CPET parameters and drug type remained significant after multivariate adjustment. Moreover, patients receiving central-acting drugs had fewer composite events (P = 0.023), and HF hospitalizations (P = 0.044), although significance after multivariant correction was not achieved, despite the hazard ratio being 0.664 and 0.757, respectively. Conclusions: Central-acting drugs were associated with better respiratory function as measured by CPET parameters in HF patients. This could extend to clinically meaningful composite outcomes and hospitalizations but required more power to be definitive in linking to drug effect. Central-acting HF drugs show a role in mitigating diaphragm weakness. Résumé: Contexte: L’atrophie du diaphragme peut contribuer à la dyspnée chez les personnes atteintes d’insuffisance cardiaque (IC), compte tenu de son lien avec la suractivation neuro-hormonale centrale. Or, les médicaments contre l’IC qui franchissent la barrière hématoencéphalique pourraient exercer une action centrale, améliorer la respiration et ainsi éventuellement atténuer l’atrophie du diaphragme. C’est pourquoi nous avons voulu comparer, au moyen d’une seule épreuve d’effort cardiopulmonaire (EECP), les effets bénéfiques exercés par des médicaments à action périphérique et des médicaments à action centrale sur la fonction respiratoire, de même que l’issue des patients atteints d’IC auxquels ils ont été administrés. Méthodologie: Nous avons réalisé une étude rétrospective auprès de 624 adultes ambulatoires atteints d’IC (80 % d’hommes) dont la fraction d’éjection ventriculaire gauche était réduite (≤ 40 %), qui se sont prêtés à une EECP complète et qui ont été suivis dans le même établissement entre 2001 et 2017. Les paramètres de l’EECP et la mortalité toutes causes confondues, un critère d’évaluation composé (décès toutes causes confondues, nécessité de recourir à un dispositif d’assistance ventriculaire gauche, transplantation cardiaque), et les hospitalisations toutes causes confondues et/ou liées à l’IC ont été comparés entre les patients qui recevaient des médicaments à action centrale (n = 550) et ceux qui recevaient des médicaments à action périphérique (n = 74). Résultats: Comparativement aux patients ayant reçu des médicaments à action périphérique, ceux qui ont reçu des médicaments à action centrale ont bénéficié d’une meilleure fonction respiratoire (consommation maximale d’oxygène [VO2], p = 0,020; volume expiratoire maximal par seconde [VEMS], p = 0,007) et d’une meilleure efficacité ventilatoire (ventilation minute/production de dioxyde de carbone [VE/VCO2], p < 0,001; pression partielle de dioxyde de carbone en fin d’expiration [PETCO2], p = 0,015; et tendance de la capacité vitale forcée [CVF], p = 0,056). De plus, bon nombre des associations entre les paramètres de l’EECP et le type de médicament sont demeurées significatives après ajustement multivarié. Les patients qui ont reçu des médicaments à action centrale ont également présenté moins d’événements faisant partie du critère d’évaluation composé (p = 0,023) et moins d’hospitalisations liées à l’IC (p = 0,044), même si la différence après correction multivariée n’a pas été significative et que les rapports de risques étaient respectivement de 0,664 et de 0,757. Conclusions: Les médicaments à action centrale ont été associés à une meilleure fonction respiratoire, mesurée à l’aide des paramètres d’une EECP, chez les patients atteints d’IC. Ce résultat pourrait également s’appliquer au critère d’évaluation composé et aux hospitalisations, mais une étude plus puissante est nécessaire pour établir un lien cliniquement significatif avec l’effet des médicaments. Les médicaments à action centrale contre l’IC ont donc un rôle à jouer dans la correction de la faiblesse du diaphragme.

Background: Severe primary graft dysfunction (PGD) after heart transplantation (HT) is a major cause of death and requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Methods: We conducted a systematic review and meta-analysis including studies of adult HT recipients who required VA-ECMO for PGD to determine whether a peripheral or central configuration was associated with higher mortality. The primary endpoints were short-term and one-year mortality. Secondary endpoints were VA-ECMO-related complications. Results: Overall, we included 16 studies comprising 874 patients from 33 centers. Using a random-effects model, peripheral cannulation was associated with a nonsignificant reduction in short-term mortality (odds ratios [OR] = 0.73, 95% confidence interval [CI] = 0.41-1.28, I2 = 55.8%) and a significant reduction in 1-year mortality (OR = 0.60, 95%CI = 0.37-0.97, I2 = 35.9%). Peripheral cannulation decreased the risk of bleeding but increased the risk of limb ischemia and infection, with similar rates of stroke and need for renal replacement therapy. Overall, certainty of evidence was low. Conclusions: With low certainty evidence, peripheral VA-ECMO cannulation may reduce short-term and 1-year mortality with lower bleeding rates but higher limb-related complications, supporting peripheral configuration in HT recipients with severe PGD.

IntroductionExercise training post-transplant has been shown to improve physical function and quality of life in solid organ transplant (SOT) recipients. Online resources in the form of websites and videos are commonly used to provide education and instruction on exercise and physical activity in SOT; however, the content and quality of these online resources has not been evaluated.MethodsThe first 200 websites and videos identified on Google and YouTube using the English search term “exercise and physical activity in solid organ transplantation” were analyzed. Website and video content was evaluated based on 25 key components of exercise and physical activity in SOT as described in established exercise program recommendations. Website and video quality was determined using DISCERN, Global Quality Scale (GQS), and Patient Education Materials and Assessment Tool (PEMAT; threshold for which material is deemed understandable or actionable is >70%). Parametric and non-parametric tests were used to assess website and video characteristics, content, and quality metrics.ResultsForty-nine unique SOT websites (n = 15) and videos (n = 34) were identified, with the two most common categories being foundation/advocacy organizations and scientific resources. The average reading grade level of websites was 13 ± 3. Website and video content scores varied significantly (websites 11.3 ± 6.4; videos 8.4 ± 5.3). DISCERN total score and GQS score were low (median range for DISCERN 2.5–3.0; median for GQS 2.0 for both websites and videos, out of 5). PEMAT understandability and actionability scores were also low across websites and videos (mean range 57%–67% and 47%–65%, respectively). Foundation/advocacy websites had higher content and quality scores compared to scientific organizations and news/media articles.ConclusionsTo our knowledge, this is the first comprehensive assessment of online content and quality of website and video resources on physical activity and exercise in adult SOT recipients. There were a limited number of online English patient-directed resources related to physical activity in SOT, most of which only partly captured items outlined in consensus exercise program recommendations and were of low quality and understandability and actionability. This work provides important insight to the English-speaking transplant community on the current state of online exercise health information and provides future direction for resource development.

Background: Multidisciplinary heart failure (HF) clinics decrease hospital admission rates and healthcare use, while improving patient outcomes. To understand the contemporary availability of HF clinics in Ontario, Canada, and the services provided, we performed an environmental scan of physician-led and nurse practitioner (NP)–led HF clinics. Methods: Between November, 2019 and February 2020, we identified Ontario HF clinics led by physicians or NPs. Following an invitation, we conducted a semi-structured interview to evaluate the services offered and qualitatively compared our findings to the results of the 2010 Ontario provincial survey. Results: The number of HF clinics (36 vs 34 in 2010) and physicians (157 vs 143 in 2010) have not changed since the 2010 survey. Of the 36 clinics we identified, 30 participated in our interview (22 physician-led and 8 NP-led). Twenty-five clinics (83%) were hospital-based, of which 9 (30%) were part of an academic institution. Comparisons of our findings to the 2010 study on 30 clinics show an approximately 3-fold increase (P

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used increasingly to support patients who are in cardiogenic shock. Due to the risk of complications, prediction models may aid in identifying patients who would benefit most from VA-ECMO. One such model is the Survival After Veno-Arterial Extracorporeal Membrane Oxygenation (SAVE) score. Therefore, we wanted to validate the utility of the SAVE score in a contemporary cohort of adult patients. Methods: Retrospective data were extracted from electronic health records of 120 patients with cardiogenic shock supported with VA-ECMO between 2011 and 2018. The SAVE score was calculated for each patient to predict survival to hospital discharge. We assessed the SAVE score calibration by comparing predicted vs observed survival at discharge. We assessed discrimination with the area under the receiver operating curve using logistic regression. Results: A total of 45% of patients survived to hospital discharge. Survivors had a significantly higher mean SAVE score (–9.3 ± 4.1 in survivors vs –13.1 ± 4.4, respectively; P = 0.001). SAVE score discrimination was adequate (c = 0.77; 95% confidence interval 0.69-0.86; P < 0.001). SAVE score calibration was limited, as observed survival rates for risk classes II-V were higher in our cohort (II: 67% vs 58%; III: 78% vs 42%; IV: 61% vs 30%; and V: 29% vs 18%). Conclusions: The SAVE score underestimates survival in a contemporary North American cohort of adult patients with cardiogenic shock. Its inaccurate performance could lead to denying ECMO support to patients deemed to be too high risk. Further studies are needed to validate additional predictive models for patients requiring VA-ECMO. Résumé: Contexte: L’oxygénation extracorporelle veino-artérielle (ECMO-VA) est de plus en plus utilisée comme assistance pour les patients qui sont en choc cardiogène. En raison du risque de complications, des modèles de prédiction peuvent aider à déterminer quels patients bénéficieraient le plus d’une ECMO-VA. Le score SAVE (Survival After Veno-Arterial Extracorporeal Membrane Oxygenation) est un modèle de ce genre. Par conséquent, nous voulions valider l’utilité du score SAVE dans une cohorte contemporaine de patients adultes. Méthodologie: Des données rétrospectives ont été extraites de dossiers médicaux électroniques de 120 patients atteints d’un choc cardiogène ayant reçu une ECMO-VA entre 2011 et 2018. Le score SAVE a été calculé pour chaque patient afin de prédire la survie au congé de l’hôpital. Nous avons évalué la calibration du score SAVE en comparant la survie prédite au moment du congé et la survie observée. Nous avons évalué la discrimination par l’aire sous la courbe opérationnelle chez le receveur en faisant appel à la régression logistique. Résultats: Au total, 45 % des patients ont survécu au congé de l’hôpital. Les survivants affichaient un score SAVE moyen considérablement plus élevé (–9,3 ± 4,1 chez les survivants vs –13,1 ± 4,4; p = 0,001). La discrimination par le score SAVE était adéquate (c = 0,77; intervalle de confiance à 95 % : 0,69 à 0,86; p < 0,001). La calibration du score SAVE était limitée, car les taux pour les classes de risque II à V étaient plus élevés dans notre cohorte (II : 67 % vs 58 %; III : 78 % vs 42 %; IV : 61 % vs 30 %; et V : 29 % vs 18 %). Conclusions: Le score SAVE sous-estime la survie dans une cohorte nord-américaine contemporaine de patients adultes atteints d’un choc cardiogène. L’inexactitude de ses résultats pourrait faire en sorte qu’une assistance par ECMO serait refusée à des patients jugés comme présentant un risque élevé. D’autres études sont nécessaires pour valider d’autres modèles de prédiction pour les patients ayant besoin d’une ECMO-VA.

Abstract Background Heart failure (HF) is a complex chronic condition, leading to frequent hospitalization, decreased quality of life, and increased mortality. Current guidelines recommend that multidisciplinary care be provided in specialized HF clinics. A number of studies have demonstrated the effectiveness of these clinics; however, there is a wide range in the services provided across different clinics. This network meta-analysis will aim to identify the aspects of HF clinic care that are associated with the best outcomes: a reduction in mortality, hospitalization, and visits to emergency department (ED) and improvements to quality of life. Methods Relevant electronic databases will be systematically searched to identify eligible studies. Controlled trials and observational cohort studies of adult (≥ 18 years of age) patients will be eligible for inclusion if they evaluate at least one component of guideline-based HF clinic care and report all-cause or HF-related mortality, hospitalizations, or ED visits or health-related quality of life assessed after a minimum follow-up of 30 days. Both controlled trials and observational studies will be included to allow us to compare the efficacy of the interventions in an ideal context versus their effectiveness in the real world. Two reviewers will independently perform both title and abstract full-text screenings and data abstraction. Study quality will be assessed through a modified Cochrane risk of bias tool for randomized controlled trials (RCTs) or the ROBINS-I tool for observational studies. The strength of evidence will be assessed using a modified Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system. Network meta-analysis methods will be applied to synthesize the evidence across included studies. To contrast findings between study designs, data from RCTs will be analyzed separately from non-randomized controlled trials and cohort studies. We will estimate both the probability that a particular component of care is the most effective and treatment effects for specified combinations of care. Discussion To our knowledge, this will be the first study to evaluate the comparative effectiveness of the different components of care offered in HF clinics. The findings from this systematic review will provide valuable insight about which components of HF clinic care are associated with improved outcomes, potentially informing clinical guidelines as well as the design of future care interventions in dedicated HF clinics. Systematic review registration PROSPERO CRD42017058003