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.

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.

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).

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.

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.

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).

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.

Outcomes Among Patients Hospitalized With Non-COVID-19 Conditions Before and During the COVID-19 Pandemic in Alberta and Ontario, Canada.

Importance: The association of inpatient COVID-19 caseloads with outcomes in patients hospitalized with non-COVID-19 conditions is unclear. Objective: To determine whether 30-day mortality and length of stay (LOS) for patients hospitalized with non-COVID-19 medical conditions differed (1) before and during the pandemic and (2) across COVID-19 caseloads. Design, Setting, and Participants: This retrospective cohort study compared patient hospitalizations between April 1, 2018, and September 30, 2019 (prepandemic), vs between April 1, 2020, and September 30, 2021 (during the pandemic), in 235 acute care hospitals in Alberta and Ontario, Canada. All adults hospitalized for heart failure (HF), chronic obstructive pulmonary disease (COPD) or asthma, urinary tract infection or urosepsis, acute coronary syndrome, or stroke were included. Exposure: The monthly surge index for each hospital from April 2020 through September 2021 was used as a measure of COVID-19 caseload relative to baseline bed capacity. Main Outcomes and Measures: The primary study outcome was 30-day all-cause mortality after hospital admission for the 5 selected conditions or COVID-19 as measured by hierarchical multivariable regression models. Length of stay was the secondary outcome. Results: Between April 2018 and September 2019, 132 240 patients (mean [SD] age, 71.8 [14.8] years; 61 493 female [46.5%] and 70 747 male [53.5%]) were hospitalized for the selected medical conditions as their most responsible diagnosis compared with 115 225 (mean [SD] age, 71.9 [14.7] years, 52 058 female [45.2%] and 63 167 male [54.8%]) between April 2020 and September 2021 (114 414 [99.3%] of whom had negative SARS-CoV-2 test results). Patients admitted during the pandemic with any of the selected conditions and concomitant SARS-CoV-2 infection exhibited a much longer LOS (mean [SD], 8.6 [7.1] days or a median of 6 days longer [range, 1-22 days]) and greater mortality (varying across diagnoses, but with a mean [SD] absolute increase at 30 days of 4.7% [3.1%]) than those without coinfection. Patients hospitalized with any of the selected conditions without concomitant SARS-CoV-2 infection had similar LOSs during the pandemic as before the pandemic, and only patients with HF (adjusted odds ratio [AOR], 1.16; 95% CI, 1.09-1.24) and COPD or asthma (AOR, 1.41; 95% CI, 1.30-1.53) had a higher risk-adjusted 30-day mortality during the pandemic. As hospitals experienced COVID-19 surges, LOS and risk-adjusted mortality remained stable for patients with the selected conditions but were higher in patients with COVID-19. Once capacity reached above the 99th percentile, patients' 30-day mortality AOR was 1.80 (95% CI, 1.24-2.61) vs when the surge index was below the 75th percentile. Conclusions and Relevance: This cohort study found that during surges in COVID-19 caseloads, mortality rates were significantly higher only for hospitalized patients with COVID-19. However, most patients hospitalized with non-COVID-19 conditions and negative SARS-CoV-2 test results (except those with HF or with COPD or asthma) exhibited similar risk-adjusted outcomes during the pandemic as before the pandemic, even during COVID-19 caseload surges, suggesting resiliency in the event of regional or hospital-specific occupancy strains.

Global Comparison of Readmission Rates for Patients With Heart Failure.

BACKGROUND: Heart failure (HF) readmission rates are low in some jurisdictions. However, international comparisons are lacking and could serve as a foundation for identifying regional patient management strategies that could be shared to improve outcomes. OBJECTIVES: This study sought to summarize 30-day and 1-year all-cause readmission and mortality rates of hospitalized HF patients across countries and to explore potential differences in rates globally. METHODS: We performed a systematic review and meta-analysis using MEDLINE, Embase, and CENTRAL for observational reports on hospitalized adult HF patients at risk for readmission or mortality published between January 2010 and March 2021. We conducted a meta-analysis of proportions using a random-effects model, and sources of heterogeneity were evaluated with meta-regression. RESULTS: In total, 24 papers reporting on 30-day and 23 papers on 1-year readmission were included. Of the 1.5 million individuals at risk, 13.2% (95% CI: 10.5%-16.1%) were readmitted within 30 days and 35.7% (95% CI: 27.1%-44.9%) within 1 year. A total of 33 papers reported on 30-day and 45 papers on 1-year mortality. Of the 1.5 million individuals hospitalized for HF, 7.6% (95% CI: 6.1%-9.3%) died within 30 days and 23.3% (95% CI: 20.8%-25.9%) died within 1 year. Substantial variation in risk across countries was unexplained by countries' gross domestic product, proportion of gross domestic product spent on health care, and Gini coefficient. CONCLUSIONS: Globally, hospitalized HF patients exhibit high rates of readmission and mortality, and the variability in readmission rates was not explained by health care expenditure, risk of mortality, or comorbidities.

The impact of obesity and LVAD-bridging on heart transplant candidate outcomes: a linked STS INTERMACS - OPTN/UNOS data analysis.

BACKGROUND: Limited data integrating waitlist and postheart transplant (HT) mortality have evaluated outcomes of left ventricular assist device (LVAD)-bridged strategy vs no LVAD according to patient characteristics. We evaluated waitlist and post-HT mortality in LVAD-bridged vs nonbridged patients based on body mass index (BMI). METHODS: We included linked adults listed for HT in Organ Procurement and Transplant Network/United Network for Organ Sharing and patients receiving durable LVAD as bridge to HT or candidacy in Society of Thoracic Surgeons/Interagency Mechanical Circulatory Support databases (2010-2019). Using BMI at listing or LVAD implant, we categorized patients as underweight (<18.5 kg/m2), normal weight (18.5-24.99 kg/m2), overweight (25-29.99 kg/m2), and obese (≥30 kg/m2). Kaplan-Meier analysis and multivariable Cox proportional hazards models informed the effect of LVAD-bridged and nonbridged strategy by BMI on waitlist, post-HT, and overall mortality (including waitlist and post-HT mortality). RESULTS: Among 11,216 LVAD-bridged and 17,122 nonbridged candidates, bridged candidates were more frequently obese (37.3% vs 28.6%) (p < 0.001). Multivariable analysis indicated increased waitlist mortality in LVAD-bridged vs nonbridged with overweight (Hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.02-1.36) or obesity (HR 1.35, 95%CI 1.17-1.56) in comparison to normal weight candidates (HR 1.02, 95%CI 0.88-1.19) (p-interaction < 0.001). Post-transplant mortality was not statistically different in LVAD-bridged vs nonbridged patients across BMI categories (p-interaction = 0.26). There was a nonsignificant graded increase in overall mortality in LVAD-bridged with overweight (HR 1.53, 95%CI 1.39-1.68) or obesity (HR 1.61, 95%CI 1.46-1.78) compared to nonbridged patients (p-interaction = 0.13). CONCLUSIONS: LVAD-bridged candidates with obesity had higher waitlist mortality compared to nonbridged candidates with obesity. Post-transplant mortality was similar in LVAD-bridged and nonbridged patients, but obesity remained associated with increased mortality in both groups. This study may aid clinicians and advanced heart failure patients with obesity in decision-making.

Predicting 1-Year Mortality in Outpatients With Heart Failure With Reduced Left Ventricular Ejection Fraction: Do Empiric Models Outperform Physician Intuitive Estimates? A Multicenter Cohort Study.

BACKGROUND: Many studies have demonstrated that physicians often err in estimating patient prognosis. No studies have directly compared physician to model predictive performance in heart failure (HF). We aimed to compare the accuracy of physician versus model predictions of 1-year mortality. METHODS: This multicenter prospective cohort study on 11 HF clinics in 5 provinces in Canada included consecutive consented outpatients with HF with reduced left ventricular ejection fraction (<40%). By collecting clinical data, we calculated predicted 1-year mortality using the Seattle HF Model (SHFM), the Meta-Analysis Global Group in Chronic HF score, and the HF Meta-Score. HF cardiologists and family doctors, blinded to model predictions, estimated patient 1-year mortality. During 1-year follow-up, we recorded the composite end point of mortality, urgent ventricular assist device implant, or heart transplant. We compared physicians and model discrimination (C statistic), calibration (observed versus predicted event rate), and risk reclassification. RESULTS: The study included 1643 patients with ambulatory HF with a mean age of 65 years, 24% female, and mean left ventricular ejection fraction of 28%. Over 1-year follow-up, 9% had an event. The SHFM had the best discrimination (SHFM C statistic 0.76; HF Meta-Score 0.73; Meta-Analysis Global Group in Chronic Heart Failure 0.70) and calibration. Physicians' discrimination differed little (0.75 for HF cardiologists and 0.73 for family doctors) but both physician groups substantially overestimated risk by >10% in both low- and high-risk patients (poor calibration). In risk reclassification analysis, among patients without events, the SHFM better classified 51% in comparison to HF cardiologists and 43% in comparison to family doctors. In patients with events, the SHFM erroneously assigned lower risk to 44% in comparison to HF cardiologists and 34% in comparison to family doctors. CONCLUSIONS: Family doctors and HF cardiologists showed adequate risk discrimination, with however substantial overestimation of absolute risk. Predictive models showed higher accuracy. Incorporating models in family and HF cardiology practices may improve patient care and resource use in HF with reduced left ventricular ejection fraction. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04009798.

Remote Monitoring for Heart Failure Management at Home.

Early telemonitoring of weights and symptoms did not decrease heart failure hospitalizations but helped identify steps toward effective monitoring programs. A signal that is accurate and actionable with response kinetics for early re-assessment is required for the treatment of patients at high risk, while signal specifications differ for surveillance of low-risk patients. Tracking of congestion with cardiac filling pressures or lung water content has shown most impact to decrease hospitalizations, while multiparameter scores from implanted rhythm devices have identified patients at increased risk. Algorithms require better personalization of signal thresholds and interventions. The COVID-19 epidemic accelerated transition to remote care away from clinics, preparing for new digital health care platforms to accommodate multiple technologies and empower patients. Addressing inequities will require bridging the digital divide and the deep gap in access to HF care teams, who will not be replaced by technology but by care teams who can embrace it.

Sex-Based Differences in Severe Outcomes, Including Cardiovascular Hospitalization, in Adults With COVID-19 in Ontario, Canada.

Background: While men have experienced higher risks of SARS-CoV-2 infection compared to women, an analysis of sex differences by age in severe outcomes during the acute phase of infection is lacking. Objectives: The purpose of this study was to assess heterogeneity in severe outcome risks by age and sex by conducting a retrospective cohort study of community-dwelling adults in Ontario who tested positive for SARS-CoV-2 infection during the first 3 waves. Methods: Adjusted odds ratios were estimated using multilevel multivariable logistic regression models including an interaction term for age and sex. The primary outcome was a composite of severe outcomes (hospitalization for a cardiovascular (CV) event, intensive care unit admission, mechanical ventilation, or death) within 30 days. Results: Among 30,736, 199,132, and 186,131 adults who tested positive during the first 3 waves, 1,908 (6.2%), 5,437 (2.7%), and 5,653 (3.0%) experienced a severe outcome within 30 days. For all outcomes, the sex-specific risk depended on age (all P for interaction <0.05). Men with SARS-CoV-2 infection experienced a higher risk of outcomes than infected women of the same age, except for the risk of all-cause hospitalization being higher for young women than men (ages 18-45 years) during waves 2 and 3. The sex disparity in CV hospitalization across all ages either persisted or increased with each subsequent wave. Conclusions: To mitigate risks in subsequent waves, it is helpful to further understand the factors that contribute to the generally higher risks faced by men across all ages, and the persistent or increasing sex disparity in the risk of CV hospitalization.

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.

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

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