Better Respiratory Function in Heart Failure Patients With Use of Central-Acting Therapeutics.

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.

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.

Transform[ing] heart failure professionals with Indigenous land-based cultural safety in Ontario, Canada.

Cardiovascular disease is a leading cause of death worldwide, with disproportionate impacts on Indigenous Peoples in Canada. In Spring 2022, a land-based learning program was piloted and evaluated as an Indigenous cultural safety training for professionals at a cardiac care centre and university in a large urban city. Baseline and endline surveys showed an increase in knowledge of Indigenous histories, cultures, and practices; increased reflection on positionality and intention to create change; and strengthened relationships with the land. Future work should explore the long-term effects of land-based cultural safety training on participant behaviours, and health outcomes for Indigenous Peoples.

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.

Predicting heart failure outcomes by integrating breath-by-breath measurements from cardiopulmonary exercise testing and clinical data through a deep learning survival neural network.

Aims: Mathematical models previously developed to predict outcomes in patients with heart failure (HF) generally have limited performance and have yet to integrate complex data derived from cardiopulmonary exercise testing (CPET), including breath-by-breath data. We aimed to develop and validate a time-to-event prediction model using a deep learning framework using the DeepSurv algorithm to predict outcomes of HF. Methods and results: Inception cohort of 2490 adult patients with high-risk cardiac conditions or HF underwent CPET with breath-by-breath measurements. Potential predictive features included known clinical indicators, standard summary statistics from CPETs, and mathematical features extracted from the breath-by-breath time series of 13 measurements. The primary outcome was a composite of death, heart transplant, or mechanical circulatory support treated as a time-to-event outcomes. Predictive features ranked as most important included many of the features engineered from the breath-by-breath data in addition to traditional clinical risk factors. The prediction model showed excellent performance in predicting the composite outcome with an area under the curve of 0.93 in the training and 0.87 in the validation data sets. Both the predicted vs. actual freedom from the composite outcome and the calibration of the prediction model were excellent. Model performance remained stable in multiple subgroups of patients. Conclusion: Using a combined deep learning and survival algorithm, integrating breath-by-breath data from CPETs resulted in improved predictive accuracy for long-term (up to 10 years) outcomes in HF. DeepSurv opens the door for future prediction models that are both highly performing and can more fully use the large and complex quantity of data generated during the care of patients with HF.

Ambulatory Cardiology or General Internal Medicine Assessment Prior to Scheduled Major Vascular Surgery is Associated with Improved Outcomes.

OBJECTIVE: To characterize the association between ambulatory cardiology or general internal medicine (GIM) assessment prior to surgery and outcomes following scheduled major vascular surgery. BACKGROUND: Cardiovascular risk assessment and management prior to high-risk surgery remains an evolving area of care. METHODS: This is population-based retrospective cohort study of all adults who underwent scheduled major vascular surgery in Ontario, Canada, April 1, 2004-March 31, 2019. Patients who had an ambulatory cardiology and/or GIM assessment within 6 months prior to surgery were compared to those who did not. The primary outcome was 30-day mortality. Secondary outcomes included: composite of 30-day mortality, myocardial infarction or stroke; 30-day cardiovascular death; 1-year mortality; composite of 1-year mortality, myocardial infarction or stroke; and 1-year cardiovascular death. Cox proportional hazard regression using inverse probability of treatment weighting (IPTW) was used to mitigate confounding by indication. RESULTS: Among 50,228 patients, 20,484 (40.8%) underwent an ambulatory assessment prior to surgery: 11,074 (54.1%) with cardiology, 8,071 (39.4%) with GIM and 1,339 (6.5%) with both. Compared to patients who did not, those who underwent an assessment had a higher Revised Cardiac Risk Index (N with Index over 2= 4,989[24.4%] vs. 4,587[15.4%], P<0.001) and more frequent pre-operative cardiac testing (N=7,772[37.9%] vs. 6,113[20.6%], P<0.001) but, lower 30-day mortality (N=551[2.7%] vs. 970[3.3%], P<0.001). After application of IPTW, cardiology or GIM assessment prior to surgery remained associated with a lower 30-day mortality (weighted Hazard Ratio [95%CI] = 0.73 [0.65-0.82]) and a lower rate of all secondary outcomes. CONCLUSIONS: Major vascular surgery patients assessed by a cardiology or GIM physician prior to surgery have better outcomes than those who are not. Further research is needed to better understand potential mechanisms of benefit.

Utilizing Quality of Life Adjusted Days Alive and Out of Hospital in Heart Failure Clinical Trials.

BACKGROUND: In heart failure (HF) trials, there has been an emphasis on utilizing more patient-centered outcomes, including quality of life (QoL) and days alive and out of hospital. We aimed to explore the impact of QoL adjusted days alive and out of hospital as an outcome in 2 HF clinical trials. METHODS: Using data from 2 trials in HF (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT] and Study of Dietary Intervention under 100 mmol in Heart Failure [SODIUM-HF]), we determined treatment differences using percentage days alive and out of hospital (%DAOH) adjusted for QoL at 18 months as the primary outcome. For each participant, %DAOH was calculated as a ratio between days alive and out of hospital/total follow-up. Using a regression model, %DAOH was subsequently adjusted for QoL measured by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score. RESULTS: In the GUIDE-IT trial, 847 participants had a median baseline Kansas City Cardiomyopathy Questionnaire Overall Summary Score of 59.0 (interquartile range, 40.8-74.3), which did not change over 18 months. %DAOH was 90.76%±22.09% in the biomarker-guided arm and 88.56%±25.27% in the usual care arm. No significant difference in QoL adjusted %DAOH was observed (1.09% [95% CI, -1.57% to 3.97%]). In the SODIUM-HF trial, 796 participants had a median baseline Kansas City Cardiomyopathy Questionnaire Overall Summary Score of 69.8 (interquartile range, 49.3-84.3), which did not change over 18 months. %DAOH was 95.69%±16.31% in the low-sodium arm and 95.95%±14.76% in the usual care arm. No significant difference was observed (1.91% [95% CI, -0.85% to 4.77%]). CONCLUSIONS: In 2 large HF clinical trials, adjusting %DAOH for QoL was feasible and may provide complementary information on treatment effects in clinical trials.

The Effect of Using a Remote Patient Management Platform in Optimizing Guideline-Directed Medical Therapy in Heart Failure Patients: A Randomized Controlled Trial.

BACKGROUND: Guideline-directed medical therapy (GDMT) remains underutilized in patients with heart failure with reduced ejection fraction, leading to morbidity and mortality. OBJECTIVES: The Medly Titrate (Use of Telemonitoring to Facilitate Heart Failure Mediation Titration) study was an open-label, randomized controlled trial to determine whether remote medication titration for patients with heart failure with reduced ejection fraction was more effective than usual care (UC). METHODS: In this study, 108 patients were randomized to remote GDMT titration through the Medly heart failure program (n = 56) vs UC (n = 52). The primary outcome was the proportion of patients completing GDMT titration at 6 months. Secondary outcomes included the number of clinic visits and time required to achieve titration, patient health outcomes, and health care utilization, including urgent clinic/emergency department visits and hospitalization. RESULTS: At 6 months, GDMT titration was completed in 82.1% (95% CI: 71.2%-90.8%) of patients in the intervention arm vs 53.8% in UC (95% CI: 41.1%-67.7%; P = 0.001). Remote titration required fewer in-person (1.62 ± 1.09 vs 2.42 ± 1.65; P = 0.004) and virtual clinic visits (0.50 ± 1.08 vs 1.29 ± 1.86; P = 0.009) to complete titration. Median time to optimization was shorter with remote titration (3.42 months [Q1-Q3: 2.99-4.04 months] vs 5.47 months [Q1-Q3: 4.14-7.33 months]; P < 0.001). The number of urgent clinic/emergency department visits (incidence rate ratio of remote vs control groups: 0.90 [95% CI: 0.53-1.56]; P = 0.70) were similar between groups, with a reduction in all-cause hospitalization with remote titration (incidence rate ratio: 0.55 [95% CI: 0.31-0.97]; P = 0.042). CONCLUSIONS: Remote titration of GDMT in heart failure with reduced ejection fraction was effective, safe, feasible, and increased the proportion of patients achieving target doses, in a shorter period of time with no excess adverse events compared with UC. (Use of Telemonitoring to Facilitate Heart Failure Mediation Titration [Medly Titrate]; NCT04205513).

Dementia and mild cognitive impairment screening in an emergency homeless shelter.

INTRODUCTION: Older adults represent the fastest growing segment of the homeless community. Little is known about the prevalence of dementia and mild cognitive impairment (MCI) in this population. METHODS: Dementia and MCI screening using the Montreal Cognitive Assessment (MoCA) was incorporated into the standard senior evaluation for adult clients aged ≥ 55 in a large emergency homeless shelter. RESULTS: In a 6-week period, 104 of 112 (92.9%) assessments were positive for dementia or MCI using a standard cutoff of 26, and 81 (72.3%) were positive using a conservative cutoff of 23. There was no significant difference in MoCA scores based on sex or education level, and no significant correlation between age and MoCA score. DISCUSSION: Older adults experiencing homelessness may have a high likelihood of dementia or MCI. Routine MoCA screening in older adults experiencing homelessness is feasible and can help to identify services needed to successfully exit homelessness.

Factors Impacting Physician Prognostic Accuracy in Heart Failure Patients With Reduced Left Ventricular Ejection Fraction.

BACKGROUND: A recent study showed that the accuracy of heart failure (HF) cardiologists and family doctors to predict mortality in outpatients with HF proved suboptimal, performing less well than models. OBJECTIVES: The authors sought to evaluate patient and physician factors associated with physician accuracy. METHODS: The authors included outpatients with HF from 11 HF clinics. Family doctors and HF cardiologists estimated patient 1-year mortality. They calculated predicted mortality using the Seattle HF Model and followed patients for 1 year to record mortality (or urgent heart transplant or ventricular assist device implant as mortality-equivalent events). Using multivariable logistic regression, the authors evaluated associations among physician experience and confidence in estimates, duration of patient-physician relationship, patient-physician sex concordance, patient race, and predicted risk, with concordant results between physician and model predictions. RESULTS: Among 1,643 patients, 1-year event rate was 10% (95% CI: 8%-12%). One-half of the estimates showed discrepant results between model and physician predictions, mainly owing to physician risk overestimation. Discrepancies were more frequent with increasing patient risk from 38% in low-risk to ∼75% in high-risk patients. When making predictions on male patients, female HF cardiologists were 26% more likely to have discrepant predictions (OR: 0.74; 95% CI: 0.58-0.94). HF cardiologist estimates in Black patients were 33% more likely to be discrepant (OR: 0.67; 95% CI: 0.45-0.99). Low confidence in predictions was associated with discrepancy. Analyses restricted to high-confidence estimates showed inferior calibration to the model, with risk overestimation across risk groups. CONCLUSIONS: Discrepant physician and model predictions were more frequent in cases with perceived increased risk. Model predictions outperform physicians even when they are confident in their predictions. (Predicted Prognosis in Heart Failure [INTUITION]; NCT04009798).

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.

Characteristics, management, and outcomes in women and men with congestive heart failure in 40 countries at different economic levels: an analysis from the Global Congestive Heart Failure (G-CHF) registry.

BACKGROUND: There is a paucity of data on the clinical characteristics, management, and outcomes of women compared with men with heart failure in low-income and middle-income countries compared with high-income countries. We examined sex differences in risk factors, clinical characteristics, and treatments, and prospectively assessed the risk of heart failure hospitalisation and mortality in patients with heart failure in 40 high-income, middle-income, and low-income countries. METHODS: Participants aged 18 years or older with heart failure were enrolled from Dec 20, 2016, to Sept 9, 2020 in the prospective Global Congestive Heart Failure (G-CHF) study from 257 centres in 40 high-income, middle-income, and low-income countries. Participants were followed up until May 25, 2023. We recorded the demographic characteristics, medical history, and treatments of participants. We prospectively recorded data on heart failure hospitalisation and mortality by sex in the overall study, according to country economic status, and according to level of left ventricular ejection fraction (LVEF). FINDINGS: 23 341 participants (9119 [39·1%] women and 14 222 [60·1%] men) were recruited and followed up for a mean of 2·6 years (SD 1·4). The mean age of women in the study was 62 years (SD 17) compared with 64 years (14) in men. Fewer women than men had an LVEF of 40% or lower (51·7% women vs 66·2% men). By contrast, more women than men had an LVEF of 50% or higher (33·2% women vs 18·6% men). Hypertensive heart failure was the most common aetiology in women (25·5% women vs 16·8% men), whereas ischaemic heart failure was the most common aetiology in men (45·6% men vs 26·6% women). Signs and symptoms of congestion were more common in women than men: 42·6% of women had a New York Heart Association functional class of III or IV compared with 37·9% of men. The use of heart failure medications and cardiac tests did not differ systematically between the sexes, although implantable cardioverter defibrillator (ICD) implantation was lower among women than men (8·7% women vs 17·2% men). The adjusted risk of heart failure hospitalisation was similar in women and men (women-to-men adjusted hazard ratio [HR] 0·99 [95% CI 0·92-1·05]). This pattern was consistent within groups of countries categorised by economic status, geographical region, and by LVEF level. However, women had a lower adjusted risk of mortality (women-to-men adjusted HR 0·79 [95% CI 0·75-0·84]) despite adjustments for prognostic factors-a pattern which was consistently observed across groups of countries irrespective of economic status, geography, and LVEF levels of patients. INTERPRETATION: The underlying cause of heart failure and ejection fraction phenotype differ between women and men, as do the severity of symptoms. Heart failure treatments (except ICD use) were not consistently in favour of one sex. Paradoxically, while the rates of hospitalisations were similar among women and men, the risk of death was lower among women. These patterns were consistent regardless of the economic status of the countries. The higher mortality among men is unexplained and warrants further study. FUNDING: Bayer.

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.

Value of Invasive Hemodynamic Assessments in Patients Supported by Continuous-Flow Left Ventricular Assist Devices.

Left ventricular assist devices (LVADs) are increasingly used in patients with end-stage heart failure (HF). There is a significant risk of HF admissions and hemocompatibility-related adverse events that can be minimized by optimizing the LVAD support. Invasive hemodynamic assessment, which is currently underutilized, allows personalization of care for patients with LVAD, and may decrease the need for recurrent hospitalizations. It also aids in triaging patients with persistent low-flow alarms, evaluating reversal of pulmonary vasculature remodeling, and assessing right ventricular function. In addition, it can assist in determining the precipitant for residual HF symptoms and physical limitation during exercise and is the cornerstone of the assessment of myocardial recovery. This review provides a comprehensive approach to the use of invasive hemodynamic assessments in patients supported with LVADs.

Prevalence of post-liver transplant complications and NASH-related cirrhosis in postmenopausal women.

INTRODUCTION AND OBJECTIVES: Compared to premenopausal women, postmenopausal women are at greater risk of developing NAFLD and NASH, two common indications for liver transplantation (LT). We aim to determine the prevalence of NASH-related cirrhosis in postmenopausal women from a cohort of LT patients and investigate their post-LT complications. MATERIALS AND METHODS: Chart review of 1200 LT patients from 2002-2020 was performed. Postmenopausal women were defined as women over 51 and compared to a control group of men over 51. Prevalence of LT indications was determined. Subgroup analysis assessed cardiovascular disease risk. BMI and ASCVD risk scores were calculated at the time of LT and after 1 year. RESULTS: 510 patients met the inclusion criteria: 189 (37.1%) women and 321 (62.9%) men. The most common indication was NASH for women (26.5%, p<0.001) and alcohol-related cirrhosis for men (23.1%). 53 men and 46 women underwent subgroup analysis. There was no significant difference in BMI or ASCVD 10-year risk post-LT between sexes. MI occurred more in men (n=9.17%) than women (n=1, 2%, p=0.015), with no significant differences in CAD, CHF, or stroke. LT complications occurred less in men (n=5.9%) than women (n=20, 43%, p=0.0001). CONCLUSIONS: Postmenopausal women were significantly more likely to have NASH as an indication for LT than men. Postmenopausal women had greater weight gain and more noncardiac complications than men. Women did not have increased cardiovascular outcomes, ASCVD risk, or mortality. Diet education and weight control in postmenopausal women with existing risk factors for NASH should be encouraged to modulate health outcomes.

Informing preconception counseling: Outcomes among female heart transplant recipients in the ISHLT registry.

BACKGROUND: The numbers of women of child-bearing age undergoing heart transplantation (HT) and female pediatric HT recipients surviving to child-bearing age have increased, along with improvements in post-transplant survival. Data regarding life expectancy and comorbidities in reproductive-aged female HT recipients are needed to inform shared decision-making at the time of preconception counseling. METHODS: The International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant Registry was investigated for HT recipients between January 1, 2000 and June 30, 2017. Women of childbearing age were defined as those aged 15-45 years, either at transplant, or at the respective post-transplant follow-up. Characteristics and outcomes of female recipients of childbearing age at transplant, 5-, 10-, and 15-year follow-up were compared to females > 45 years of age, males 15-45 years and males > 45 years of age at the corresponding time intervals. Outcomes included survival, development of diabetes (DM), severe renal dysfunction (CKD), and cardiac allograft vasculopathy (CAV). RESULTS: During the study period, 71,585 HT recipients were included: 24% (n = 17,194) were female and 9.2% (n = 6602) were of childbearing age at HT. A pre-transplant diagnosis of peripartum cardiomyopathy was associated with significantly worse post-transplant survival, a finding that remained independent of panel reactive antibody levels. The presence of pre-transplant DM and/or severe CKD was significantly associated with lower survival as were the presence of CAV, DM, and CKD post-HT. CONCLUSION: Knowledge of the impact of pre-existing comorbidities and complications post-HT on survival are important for risk stratification for preconception counseling post-HT.

Association of neighbourhood-level material deprivation with adverse outcomes and processes of care among patients with heart failure in a single-payer healthcare system: A population-based cohort study.

AIM: We studied the association between neighbourhood material deprivation, a metric estimating inability to attain basic material needs, with outcomes and processes of care among incident heart failure patients in a universal healthcare system. METHODS AND RESULTS: In a population-based retrospective study (2007-2019), we examined the association of material deprivation with 1-year all-cause mortality, cause-specific hospitalization, and 90-day processes of care. Using cause-specific hazards regression, we quantified the relative rate of events after multiple covariate adjustment, stratifying by age ≤65 or ≥66 years. Among 395 763 patients (median age 76 [interquartile range 66-84] years, 47% women), there was significant interaction between age and deprivation quintile for mortality/hospitalization outcomes (p ≤ 0.001). Younger residents (age ≤65 years) of the most versus least deprived neighbourhoods had higher hazards of all-cause death (hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.10-1.29]) and cardiovascular hospitalization (HR 1.29 [95% CI 1.19-1.39]). Older individuals (≥66 years) in the most deprived neighbourhoods had significantly higher hazard of death (HR 1.11 [95% CI 1.08-1.14]) and cardiovascular hospitalization (HR 1.13 [95% CI 1.09-1.18]) compared to the least deprived. The magnitude of the association between deprivation and outcomes was amplified in the younger compared to the older age group. More deprived individuals in both age groups had a lower hazard of cardiology visits and advanced cardiac imaging (all p < 0.001), while the most deprived of younger ages were less likely to undergo implantable cardioverter-defibrillator/cardiac resynchronization therapy-pacemaker implantation (p = 0.023), compared to the least deprived. CONCLUSION: Patients with newly-diagnosed heart failure residing in the most deprived neighbourhoods had worse outcomes and reduced access to care than those less deprived.

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).

Heart Health Begins With Community: Community-Based Research Exploring Innovative Strategies to Support First Nations Heart Health.

Background: Indigenous people have displayed their strength through their holistic practices and spiritual connection to the land. Despite overcoming the impact of discriminatory and disempowering policies within Western institutions, Indigenous people continue to experience a higher risk of cardiovascular disease, compared to the general population. To move toward improving Indigenous health outcomes, researchers need to work in partnership with communities to develop heart health strategies centred on their experienced barriers and sources of healing. We conducted a community-based explorative study in Moosonee, Ontario to explore the local community's needs and priorities regarding heart health and wellness. Methods: A convenience sample of community members and healthcare professionals were invited to participate in a sharing circle. Qualitative data were analyzed using conventional content analysis and the Indigenous method of two-eyed seeing. Results: Eight community members and 5 healthcare professionals participated in the sharing circle. Four dominant themes were identified: (1) heart health is more than metrics; (2) honouring our traumas; (3) destigmatizing care through relationship building; and (4) innovative solutions start with community. With the history of mistreatment among Indigenous people, strength-based solutions involved rebuilding clinical relationships. To bring care closer to home, digital health tools were widely accepted, but the design of these tools needs to integrate both Western and Indigenous approaches to healing. Conclusions: Indigenous health upholds the physical, emotional, psychological, and spiritual needs of an individual as being of equal importance. To improve community heart health, strategies should start by strengthening broken bonds and bridging multiple worldviews of healing.

Contexte: Les peuples autochtones tirent une grande force de leurs pratiques holistiques et de leur lien spirituel avec le territoire, et même s'ils ont surmonté les répercussions des politiques discriminatoires et marginalisantes des institutions occidentales, ils présentent encore un risque de maladies cardiovasculaires supérieur à celui de la population générale. Afin d'aider à améliorer la santé cardiovasculaire des Autochtones, les chercheurs doivent travailler avec les communautés pour mettre en place des stratégies qui tiennent compte des obstacles en matière de soins de santé et des méthodes de guérison traditionnelles. Nous avons réalisé une étude exploratoire en milieu communautaire à Moosonee (Ontario) dans le but d'explorer les besoins et les priorités de la communauté locale en matière de santé cardiovasculaire et de bien-être. Méthodologie: Des membres de la communauté et des professionnels de la santé ont été invités à participer à un cercle de partage. Les données qualitatives ont été analysées au moyen d'une analyse classique et de la méthode autochtone dite à double perspective. Résultats: Huit membres de la communauté et cinq professionnels de la santé ont participé au cercle de partage. Quatre principaux thèmes ont été abordés : 1) la santé cardiovasculaire va au-delà de ce qui se mesure; 2) il faut tenir compte des traumatismes; 3) il faut déstigmatiser les soins en nouant des relations et 4) les solutions novatrices doivent reposer sur la participation de la communauté. En raison du passé de maltraitance envers les peuples autochtones, les solutions axées sur les forces devaient permettre de restaurer la confiance envers les soins cliniques. Les outils de santé numérique, bien adaptés aux besoins de la communauté, ont été largement acceptés, mais ils doivent intégrer les méthodes de soins occidentales et autochtones. Conclusions: Selon la vision autochtone, la santé repose en parts égales sur les aspects physiques, émotionnels, psychologiques et spirituels d'une personne. L'amélioration de la santé cardiovasculaire des membres de la communauté passe donc avant tout par des stratégies qui permettent de recréer les liens qui ont été brisés et qui intèrent plusieurs visions thérapeutiques.

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.