<div><h4>Comparison of 30-day Readmission Rates and Inpatient Cardiac Procedures for Weekday versus Weekend Hospital Admissions for Heart Failure.</h4><i>Aliyev N, Almani MU, Qudrat-Ullah M, Butler J, Khan MS, Greene SJ</i><br /><b>Background</b><br />Whether timing of hospital presentation impacts care delivery and clinical outcomes for patients hospitalized for heart failure (HF) remains a matter of debate. In this study, we examined all-cause and HF-specific 30-day readmission rates for patients who were admitted for HF on a weekend versus admitted for HF on a weekday.<br /><b>Methods</b><br />We conducted a retrospective analysis using the 2010 - 2019 Nationwide Readmission Database to compare 30-day readmission rates among patients who were admitted for HF on a weekday (Monday-Friday) versus patients who were admitted for HF on a weekend (Saturday-Sunday). We also compared in-hospital cardiac procedures and temporal trends in 30-day readmission by day of index hospital admission.<br /><b>Results</b><br />Among 8,270,717 index HF hospitalizations, 6,302,775 were admitted on weekday and 1,967,942 admitted on a weekend. For weekday and weekend admissions, the 30-day all-cause readmission rates were 19.8% versus 20.3%, and HF-specific readmission rates were 8.1% versus 8.4%, respectively. Weekend admissions were independently associated with higher risk of all-cause (aOR 1.04, 95% CI 1.03 - 1.05, p<0.001) and HF-specific readmission (aOR 1.04, 95% CI 1.03 - 1.05, p<0.001). Weekend HF admissions were less likely to undergo echocardiography (aOR 0.95, 95% CI 0.94 - 0.96, p<0.001), right heart catheterization (aOR 0.80, 95% CI 0.79 - 0.81, p<0.001), electrical cardioversion (aOR 0.90, 95% CI 0.88 - 0.93, p<0.001) and temporary mechanical support devices (aOR 0.84, 95% CI 0.79 - 0.89, p<0.001). Mean length of stay was shorter for weekend HF admissions (5.1 versus 5.4 days, p<0.001). Between 2010 and 2019, 30-day all-cause (18.5% to 18.2%, trend p<0.001) and HF-specific (8.4% to 8.3%, trend p <0.001) readmission rates decreased among weekday HF admissions. Among weekend HF admissions, the HF-specific 30-day readmission rate decreased (8.8% to 8.7%, trend p<0.001), but all-cause 30-day readmission rate remained stable (trend p=0.280).<br /><b>Conclusions</b><br />Among patients hospitalized for HF, weekend admissions were independently associated with excess risk of 30-day all-cause and HF-specific readmission and lower likelihood of undergoing in-hospital cardiovascular testing and procedures. The 30-day all-cause readmission rate has decreased modestly over time among patients admitted on weekdays, but has remained stable among patients admitted on weekends.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 25 May 2023; epub ahead of print</small></div>

<div><h4>Impact of Donor Hemodynamics on Recipient Survival in Heart Transplantation.</h4><i>Fu S, Inampudi C, Ramu B, Gregoski MJ, ... Cogswell RJ, Tedford RJ</i><br /><b>Background</b><br />While heart transplantation is the gold standard therapy for end-stage heart failure, rates of donor heart utilization remain low due to various factors that are often not evidence-based. The impact of donor hemodynamics obtained via right heart catheterization on recipient survival remains unclear.<br /><b>Methods</b><br />The United Network for Organ Sharing (UNOS) registry was used to identify donors and recipients from September 1999 to December 2019. Donor hemodynamic data were obtained and analyzed using univariate and multivariable logistical regression with the primary endpoints being 1- and 5-year post-transplant survival.<br /><b>Results</b><br />Among the 85,333 donors consented for heart transplantation during the study period, 6,573 (7.7%) underwent right heart catheterization, of which 5,531 eventually underwent procurement and transplantation. Donors were more likely to undergo right heart catheterization if they had high-risk criteria. Recipients who had donor hemodynamic assessment had similar 1- and 5-year survival to those without donor hemodynamic assessment (87% vs 86%, 1-year).<br /><b>Conclusions</b><br />Abnormal hemodynamics were common in donor hearts but did not impact recipient survival, even when risk-adjusted in multivariable analysis. Donors with abnormal hemodynamics may represent an opportunity to expand the pool of viable donor hearts.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 23 May 2023; epub ahead of print</small></div>

<div><h4>Left Atrial Function in Patients with Titin Cardiomyopathy.</h4><i>Henkens MTHM, Raafs AG, van Loon T, Vos JL, ... Lumens J, Verdonschot JAJ</i><br /><b>Background</b><br />Truncating titin variants (TTNtv) are the most prevalent genetic etiology of dilated cardiomyopathy (DCM). While TTNtv has been associated with atrial fibrillation, it remains unknown whether and how left atrial (LA) function differs between DCM patients with and without TTNtv. We aimed to determine and compare LA function in DCM patients with and without TTNtv and to evaluate whether and how left ventricular (LV) function affects the LA using computational modeling.<br /><b>Methods & results</b><br />DCM patients from the Maastricht DCM registry that underwent genetic testing and cardiovascular magnetic resonance (CMR) imaging were included in the current study. Subsequent computational modeling (CircAdapt model) was performed to identify potential LV and LA myocardial hemodynamic substrates.<br /><b>Results</b><br />In total, 377 DCM patients (N=42 with TTNtv; N=335 without a genetic variant) were included (median age 55 years, IQR [46-62], 62% men). TTNtv patients had a larger LA-volume, and reduced LA-strain compared to patients without a genetic variant (LA-volume index 60mLm<sup>-2</sup>[49;83] vs 51mLm<sup>-2</sup>[42;64];LA reservoir strain 24%[10;29] vs 28%[20;34];LA-booster strain 9%[4;14] vs 14%[10;17], respectively; all P<0.01). Computational modeling suggests that while the observed LV-dysfunction partially explains the observed LA-dysfunction in the TTNtv patients, both intrinsic LV- and LA-dysfunction are present in patients with and without a TTNtv.<br /><b>Conclusion</b><br />DCM patients with TTNtv have more severe LA dysfunction compared to patients without a genetic variant. Insights from computational modeling suggest that both intrinsic LV and LA dysfunction are present in DCM patients with and without TTNtv.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 23 May 2023; epub ahead of print</small></div>

<div><h4>Association Between Change in Ambulatory Pulmonary Artery Pressures and Natriuretic Peptides in Patients with Heart Failure: Results from the EMBRACE-HF Trial.</h4><i>Nassif ME, Nguyen D, Spertus JA, Gosch KL, ... Sauer AJ, Kosiborod MN</i><br /><b>Background</b><br />Remote monitoring of pulmonary artery (PA) pressures and serial NT-proBNP measurements guide heart failure (HF) treatment, but their association has yet to be described.<br /><b>Methods</b><br />In the Empagliflozin Evaluation by Measuring the Impact on Hemodynamics in Patients with Heart Failure (EMBRACE-HF) trial, patients with HF and a remote PA pressure monitoring device were randomized to empagliflozin versus placebo. PA diastolic pressures (PADP) and NT-proBNP levels were obtained at baseline, 6 and 12 weeks. We used linear mixed models to examine the association between change in PADP and change in NT-proBNP, adjusting for baseline covariates.<br /><b>Results</b><br />Of 62 patients, the mean age was 66.2 years, and 63% were male. The mean baseline PADP was 21.8 ± 6.4 mmHg, and the mean NT-proBNP was 1844.6 ± 2767.7 ρg/mL. The mean change between baseline and averaged 6- and 12-week PADP was -0.4 ± 3.1 mmHg, and the mean change between baseline and averaged 6- and 12-week NT-proBNP was -81.5 ± 878.6 ρg/mL. In adjusted analyses, every two mmHg decrease in PADP was associated with an NT-proBNP reduction of 108.9 ρg/mL (95% CI -4.3-222.0, p = 0.06).<br /><b>Conclusion</b><br />We observed that short-term reductions in ambulatory PADP appear to be associated with decreases in NT-proBNP. This finding may provide additional clinical context when tailoring treatment for patients with heart failure.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 23 May 2023; epub ahead of print</small></div>

<div><h4>Fewer worsening heart failure events with HeartLogic on top of standard of care: a propensity-matched cohort analysis.</h4><i>Feijen M, Beles M, Tan YZ, Cordon A, ... Beeres SLMA, Heggermont WA</i><br /><b>Background</b><br />The implantable cardiac defibrillator (ICD) based HeartLogic<sup>TM</sup> algorithm aims to detect impending fluid retention in heart failure (HF) patients. Studies show that HeartLogic<sup>TM</sup> is safe to integrate in clinical practice. The current study investigates if HeartLogic<sup>TM</sup> provides clinical benefit on top of standard care and device telemonitoring in HF patients.<br /><b>Methods</b><br />A multicenter retrospective propensity-matched cohort analysis was performed in HF patients with and ICD and compared HeartLogic<sup>TM</sup> to conventional telemonitoring. Primary endpoint was the number of worsening HF events. HF hospitalizations and ambulatory HF visits were also evaluated.<br /><b>Results</b><br />Propensity score matching yielded 127 pairs (median age 68 years, 80% male). Worsening HF events occurred more frequently in the control group (2, IQR 0-4) compared to the HeartLogic<sup>TM</sup> group (1, IQR 0-3, p=0.004). The number of HF hospitalization days was higher in controls compared to the HeartLogic<sup>TM</sup> group (8, IQR 5-12 vs. 5, IQR 2-7, p=0.023) and ambulatory visits for diuretic escalation were more frequent in the control group than in the HeartLogic<sup>TM</sup> group (2, IQR 0-3 vs. 1, IQR 0-2, p=0.0001).<br /><b>Conclusion</b><br />Integrating the HeartLogic<sup>TM</sup> algorithm in a well-equipped HF care path on top of standard care, is associated with fewer worsening HF events and shorter duration of fluid retention related hospitalizations.<br /><br />Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Card Fail: 21 May 2023; epub ahead of print</small></div>

<div><h4>Association Between Participation in a Heart Failure Telemonitoring Program and Healthcare Utilization and Death within an Integrated Health Care Delivery System.</h4><i>Parikh RV, Axelrod AW, Ambrosy AP, Tan TC, ... Dinh HH, Go AS</i><br /><b>Background</b><br />The clinical utility of remote telemonitoring to reduce post-discharge healthcare utilization and death in adults with heart failure (HF) remains controversial.<br /><b>Methods and results</b><br />Within a large integrated health care delivery system, we matched patients enrolled in a post-discharge telemonitoring intervention from 2015-2019 to patients not receiving telemonitoring at up to a 1:4 ratio on age, sex, and calipers of a propensity score. Primary outcomes were readmissions for worsening heart failure (WHF) and all-cause death within 30, 90, and 365 days of index discharge; secondary outcomes were all-cause readmissions and any outpatient diuretic dose adjustments. We matched 726 patients receiving telemonitoring to 1985 controls not receiving telemonitoring, with a mean (SD) age of 75 (11) years and 45% female. Patients receiving telemonitoring did not have a significant reduction in WHF hospitalizations (adjusted rate ratio [aRR]: 0.95, 95% confidence interval [CI]: 0.68, 1.33), all-cause death (adjusted hazard ratio: 0.60, 95% CI: 0.33, 1.08), or all-cause hospitalization (aRR: 0.82, 95% CI: 0.65, 1.05) at 30 days, but did have an increase in outpatient diuretic dose adjustments (aRR: 1.84, 95% CI: 1.44, 2.36). All associations were similar at 90- and 365-days post-discharge.<br /><b>Conclusions</b><br />A post-discharge HF telemonitoring intervention was associated with more diuretic dose adjustments but was not significantly associated with HF-related morbidity and mortality.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 21 May 2023; epub ahead of print</small></div>

<div><h4>Duration of Heart Failure with Preserved Ejection Fraction and Outcomes with Sacubitril/Valsartan: Insights from the PARAGON-HF Trial.</h4><i>Ostrominski JW, Claggett BL, Packer M, Pfeffer MA, ... Solomon SD, Vaduganathan M</i><br /><b>Aims</b><br />In this post hoc analysis of the PARAGON-HF trial, we evaluated clinical outcomes and response to sacubitril/valsartan by duration of heart failure (HF) with left ventricular ejection fraction ≥45% from initial diagnosis.<br /><b>Methods and results</b><br />The primary outcome was a composite of total HF hospitalizations and cardiovascular death, analyzed using a semiparametric proportional rates method, stratified by geographic region. Among 4,784 (99.7%) randomized PARAGON-HF participants for whom baseline HF duration was captured, 1,359 (28%) had a HF duration of <6 months, 1,295 (27%) 6 months-2 years, and 2,130 (45%) >2 years. Longer HF duration was associated with higher comorbidity burden, worse health status, and a lower rate of prior HF hospitalization. Over a median follow-up of 35 months, longer HF duration was associated with a higher risk of first and recurrent primary events (per 100 patient-years): <6 months, 12.0 (95% CI, 10.4-14.0); 6 months-2 years, 12.2 (10.6-14.2); >2 years, 15.8 (14.2-17.5). Relative treatment effects of sacubitril/valsartan vs. valsartan were consistent irrespective of baseline HF duration on the primary endpoint (P<sub>interaction</sub>=0.112). Clinically meaningful (≥5 point) improvements in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score were also similarly observed irrespective of HF duration; P<sub>interaction</sub>=0.112). Adverse events were similar between treatment arms across HF duration categories.<br /><b>Conclusions</b><br />In PARAGON-HF, longer HF duration was independently predictive of adverse HF outcomes. Treatment effects of sacubitril/valsartan were consistent irrespective of baseline HF duration, suggesting that even ambulatory patients with longstanding HFpEF and predominantly mild symptoms stand to benefit from treatment optimization.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 19 May 2023; epub ahead of print</small></div>

<div><h4>Voice-Assisted Artificial Intelligence Enabled Screening for SARS-CoV-2 Exposure in Cardiovascular Clinics: Primary results of the VOICE-COVID-19-II Randomized Trial.</h4><i>Sharma A, Marques P, Zhang G, Oulousian E, ... Razaghizad A, Avram R</i><br /><b>Background</b><br />Voice-assisted artificial intelligence (AI)-based systems may streamline clinical care among patients with heart failure (HF) and caregivers; however, randomized clinical trials are needed. We evaluated the potential for Amazon Alexa® (Alexa), a voice-assisted AI-based system, to conduct screening for SARS-CoV2 in a HF clinic.<br /><b>Methods and results</b><br />We enrolled 52 participants (patients and caregivers) from a HF clinic, who were randomly assigned with a subsequent cross-over to receive a SARS-CoV-2 screening questionnaire via Alexa or healthcare personnel. Primary outcome was overall response concordance, as measured by the percentage of agreement and unweighted kappa scores between groups. A post-screening survey evaluated comfort with using the AI-based device. In total, 36 (69%) participants were male, the median age was 51 (34-65) years and 36 (69%) were English-speaking. Twenty-one (40%) participants were HF patients. For the primary outcome, there were no statistical differences between groups: Alexa - Research coordinator group 96.9% agreement and unweighted kappa score of 0.92 (CI 0.84-1.00) versus Research coordinator - Alexa group 98.5% agreement and unweighted kappa score of 0.95 (CI 0.88-1.00) (p-value for all comparisons > 0.05). Overall, 87% of participants rated their screening experience as good or outstanding.<br /><b>Conclusion</b><br />Alexa demonstrated comparable performance to a healthcare professional for SARS-CoV2 screening in a group of HF patients and caregivers and may represent an attractive approach to symptoms screening in this population. Future studies evaluating such technologies for other uses among patients with HF and caregivers are warranted. NCT04508972.<br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>J Card Fail: 18 May 2023; epub ahead of print</small></div>

<div><h4>Pulmonary Artery Catheter Use and Risk of In-Hospital Death in Heart Failure Cardiogenic Shock.</h4><i>Kanwar MK, Blumer V, Zhang Y, Sinha S, ... Burkhoff D, Kapur NK</i><br /><b>Background</b><br />Pulmonary artery catheters (PACs) are increasingly used to guide management decisions in cardiogenic shock (CS).<br /><b>Objectives</b><br />The goal of this study was to determine if PAC use was associated with a lower risk of in-hospital mortality in CS due to acute heart failure (HF-CS).<br /><b>Methods</b><br />Multicenter, retrospective, observational study of CS patients hospitalized between 2019-2021 at 15 US hospitals participating in the Cardiogenic Shock Working Group registry. The primary endpoint was in-hospital mortality. Inverse probability of treatment-weighted logistic regression models were used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CI), accounting for multiple variables at admission. The association between timing of PAC placement and in-hospital death was also analyzed.<br /><b>Results</b><br />A total of 1055 HF-CS patients were included of whom 834 (79%) received a PAC during their hospitalization. In-hospital mortality risk for the cohort was 24.7% (n=261). PAC use was associated with lower adjusted in-hospital mortality risk (22.2% vs. 29.8%, OR 0.68, 95% CI 0.50-0.94). Similar associations were found across SCAI stages of shock, both at admission and at maximum SCAI stage during hospitalization. Early PAC use (≤ 6 hours of admission) was observed in 220 (26%) PAC recipients and associated with a lower adjusted risk of in-hospital mortality compared to delayed (≥ 48 hours) or no PAC use (17.3% vs. 27.7%, OR 0.54, 95% CI 0.37-0.81).<br /><b>Conclusions</b><br />This observational study supports PAC use, as it was associated with decreased in-hospital mortality in HF-CS, especially if performed within 6 hours of hospital admission.<br /><b>Condensed abstract</b><br />An observational study from the Cardiogenic Shock Working Group registry of 1,055 patients with heart failure related cardiogenic shock showed that pulmonary artery catheter (PAC) use was associated with lower adjusted in-hospital mortality risk (22.2% vs. 29.8%, OR 0.68, 95% CI 0.50-0.94) compared to outcomes in patients managed without PAC. Early PAC use (≤ 6 hours of admission) was associated with a lower adjusted risk of in-hospital mortality compared to delayed (≥ 48 hours) or no PAC use (17.3% vs. 27.7%, OR 0.54, 95% CI 0.37-0.81).<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 13 May 2023; epub ahead of print</small></div>

<div><h4>Contemporary care and outcomes of critically ill children with clinically diagnosed myocarditis.</h4><i>Peng DM, Kwiatkowski DM, Lasa JJ, Zhang W, ... Gaies MG, Schumacher KR</i><br /><b>Purpose</b><br />To describe contemporary management and outcomes in children with myocarditis admitted to the cardiac intensive care unit (CICU) and to identify characteristics associated with mortality.<br /><b>Methods</b><br />All patients in the Pediatric Cardiac Critical Care Consortium (PC<sup>4</sup>) registry from 8/2014-6/2021 diagnosed with myocarditis were included. Univariable analyses and multivariable logistic regression evaluated factors associated with in-hospital mortality.<br /><b>Results</b><br />There were 847 CICU admissions for myocarditis in 51 centers. Median age was 12 years (IQR 2.7-16). In-hospital mortality occurred in 53 patients (6.3%) and 60 (7.1%) had cardiac arrest during the admission. Mechanical ventilation was required in 339 patients (40%) and mechanical circulatory support (MCS) in 177 (21%): extracorporeal membrane oxygenation (ECMO)-only in 142 (16.7%), ECMO-to-ventricular assist device (VAD) in 20 (2.4%), extracorporeal cardiac resuscitation (eCPR) in 43 (5%), VAD-only in 15 (1.8%) patients. MCS was associated with in-hospital mortality; 20.3% receiving MCS died compared to 2.5% without MCS (p<0.001). Mortality was similar between ECMO-only, ECMO-to-VAD, and VAD-only groups. Median time from CICU admission to ECMO was 2.0 hours (IQR 0-9.4) and to VAD was 9.9 days (IQR 6.3-16.8). Time to MCS was not associated with mortality. In multivariable modeling of patient characteristics, smaller body surface area (BSA) and low eGFR were independently associated with mortality, and after including critical therapies, mechanical ventilation or ECMO were independent predictors of mortality.<br /><b>Conclusion</b><br />This contemporary cohort of children admitted to the CICU with myocarditis frequently received high-resource therapies however, most patients survived to hospital discharge and rarely received VAD. Smaller patient size, acute kidney injury, and receipt of mechanical ventilation or ECMO were independently associated with mortality.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 05 May 2023; epub ahead of print</small></div>

<div><h4>RIGHT HEART ADAPTATION TO EXERCISE IN PULMONARY HYPERTENSION: AN INVASIVE HEMODYNAMIC STUDY.</h4><i>Baratto C, Caravita S, Dewachter C, Faini A, ... Parati G, Vachiéry JL</i><br /><b>Background</b><br />Right heart failure (RHF) is associated with a dismal prognosis in patients with pulmonary hypertension (PH). Exercise right heart catheterization (RHC) may unmask right heart maladaptation as a sign of RHF.<br /><b>Aim</b><br />We sought to: i) define the normal limits of RAP increase during exercise; ii) describe the right heart adaptation to exercise in PH due to heart failure with preserved ejection fraction (PH-HFpEF) and in pulmonary arterial hypertension (PAH); iii) identify the factors associated with right heart maladaptation during exercise.<br /><b>Methods</b><br />We analyzed rest and exercise RHC from patients with PH-HFpEF and PAH. Right heart adaptation was described by absolute or CO-normalized changes of RAP during exercise. Individuals with non-cardiac dyspnea (NCD) served to define abnormal RAP responses (>97.5° percentile).<br /><b>Results</b><br />30 PH-HFpEF, 30 PAH and 21 NCD were included. PH-HFpEF were older than PAH, with more cardiovascular comorbidities, and higher prevalence of severe tricuspid regurgitation (TR) (p<0.05). The upper limit of normal for peak RAP and RAP/CO slope in NCD were >12 mmHg and ≥1.30 mmHg/L/min, respectively. PH-HFpEF had higher peak RAP and RAP/CO slope than PAH (20 [16-24] vs 12 [9-19] mmHg and 3.47 [2.02-6.19] vs 1.90 [1.01-4.29] mmHg/L/min, p<0.05). A higher proportion of PH-HFpEF had RAP/CO slope and peak RAP above normal (p<0.001). Estimated stressed blood volume (eSBV) at peak exercise was higher in PH-HFpEF than PAH (p<0.05). In the whole PH cohort, RAP/CO slope was associated with age, the rate of increase in eSBV during exercise, severe TR, and right atrial dilation.<br /><b>Conclusions</b><br />PH-HFpEF display a steeper increase of RAP during exercise than PAH. Preload-mediated mechanisms may play a role in the development of exercise-induced RHF.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 05 May 2023; epub ahead of print</small></div>

<div><h4>Genetic Testing for Cardiomyopathy in Japan 2022: Current Status and Issues of Precision Medicine.</h4><i>Kubo T, Kitaoka H</i><br /><AbstractText>Although many causative genes for primary cardiomyopathy have been identified, the use of genetic testing in routine practice is limited in Japan presently. Genetic diagnosis has been reported to be useful for early diagnosis through cascade genetic screening in the family, differentiating secondary cardiomyopathies, and predicting prognosis in some patients; nonetheless, the acquisition of genetic information for cardiomyopathy is stagnating in actual clinical practice. There seem to be a number of reasons for this phenomenon, and although the use of next-generation sequencers has resolved some of the past issues, the importance of pathogenicity studies of variants that are identified is growing. To ensure that patients with cardiomyopathy and their relatives can receive precision medicine, the results of genetic analysis linked to clinical information need to be collected, and a database of variants in Japanese people needs to be established.</AbstractText><br /><br />Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Card Fail: 01 May 2023; 29:805-814</small></div>

<div><h4>The influence of body mass index on clinical interpretation of established and novel biomarkers in acute heart failure.</h4><i>Horiuchi Y, Wettersten N, van Veldhuisen DJ, Mueller C, ... Murray PT, Maisel A</i><br /><b>Background</b><br />Body mass index (BMI) is a known confounder for natriuretic peptides but its influence on other biomarkers is less well described. We investigated whether BMI interacts with biomarkers association with prognosis in patients with acute heart failure (AHF).<br /><b>Methods and results</b><br />B-type natriuretic peptide (BNP), high-sensitivity cardiac troponin I (hs-cTnI), galectin-3, serum neutrophil gelatinase associated lipocalin (sNGAL) and urine NGAL were measured serially in AHF patients during hospitalization in the AKINESIS study. Cox regression analysis was used to determine the association of biomarkers and their interaction with BMI for 30-day, 90-day and 1-year composite outcome of death or HF readmission. Among 866 patients, 21.2%, 29.7%, and 46.8% had normal (18.5-24.9 kg/m<sup>2</sup>), overweight (25-29.9 kg/m<sup>2</sup>), and obese (≥30 kg/m<sup>2</sup>) BMIs on admission, respectively. Admission values of BNP and hs-cTnI were negatively associated with BMI, while galectin-3 and sNGAL were positively associated with BMI. Admission BNP and hs-cTnI were associated with the composite outcome within 30-day, 90-day and 1-year. Only BNP had a significant interaction with BMI. When BNP was analyzed by BMI category, its association with the composite outcome attenuated at higher BMIs and was no longer significant in obese individuals. Findings were similar when evaluated by the last measured biomarkers and BMI.<br /><b>Conclusions</b><br />In patients with AHF, only BNP had a significant interaction with BMI for the outcomes with its association attenuating as BMI increased. hs-cTnI was prognostic regardless of BMI.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 29 Apr 2023; epub ahead of print</small></div>

<div><h4>Relationship of Vascular Endothelial Growth Factor C, a Lymphangiogenesis Modulator, with Edema Formation, Congestion and Outcomes in Acute Heart Failure.</h4><i>Iwanek G, Ponikowska B, Zdanowicz A, Fudim M, ... Ponikowski P, Biegus J</i><br /><b>Lay summary</b><br />Acute heart failure (AHF) is a state accompanied by lymphatic system dysregulation. Current knowledge of lymphatic system involvement in the episode of AHF is limited. The lymphatic system is known to be highly responsible for edema formation. In our work, we focused on the analysis of the Vascular Endothelial Growth Factor C (VEGF-C), a known factor responsible for lymphatic system development with AHF symptoms and survival. Our studies presented that low VEGF-C serum levels on admission are associated with more severe signs of accompanying AHF fluid accumulation (defined as ascites and lower extremities edema) and higher mortality rates when compared to medium and high VEGF-C serum levels on admission. Our conclusion is that VEGF-C may be used as a parameter that reflects lymphatic system function in AHF.<br /><b>Background</b><br />Although VEGF-C is a known lymphangiogenesis modulator, its relationship with congestion formation and outcomes in AHF is unknown.<br /><b>Methods</b><br />Serum VEGF-C level was measured in 237 patients hospitalized for AHF. The population was stratified by VEGF-C levels and linked with clinical signs of congestion and outcomes.<br /><b>Results</b><br />The study population was divided in VEGF-C tertiles: low (median [Q25-Q75]: 33 [15-175]), medium (606 [468-741]) and high (1141 [968-1442] pg/ml). Low VEGF-C group on admission presented the highest prevalence of severe lower extremity edema (low VEGF-C vs medium VEGF-C vs high VEGF-C): 30% vs 13% vs 20%, p=0.02, the highest percentage of patients with ascites: 22% vs 9% vs 6%, p=0.006 and the lowest proportion of patients with pulmonary congestion: 22% vs 30% vs 46%, p=0.004. The one-year mortality was the highest in low VEGF-C tertile: 35% vs 28% vs 18%, respectively, p=0.049; the same pattern was observed for the composite endpoint (death and AHF rehospitalization): 45% vs 43% vs 26%, p=0.029. The risks of death at one-year follow-up and composite endpoint were significantly lower in the high VEGF-C group.<br /><b>Conclusions</b><br />Low VEGF-C was associated with more severe signs of congestion (signs of fluid accumulation) and adverse clinical outcomes.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 28 Apr 2023; epub ahead of print</small></div>

<div><h4>Clinical and echocardiographic diversity associated with physical fitness in the Project Baseline Health Study: implications for heart failure staging.</h4><i>Cauwenberghs N, Haddad F, Daubert MA, Chatterjee R, ... Douglas PS, Project Baseline Health Study Investigators</i><br /><b>Background</b><br />Clinical and echocardiographic features may carry diverse information on the development of heart failure (HF). Therefore, we determined heterogeneity in clinical and echocardiographic phenotypes and its association with exercise capacity.<br /><b>Methods</b><br />In 2036 community-dwelling individuals, we defined echocardiographic profiles of left and right heart remodeling and dysfunction. We subdivided the cohort based on presence (+) or absence (-) of HF risk factors and echocardiographic abnormalities (RF-/Echo-, RF-/Echo+, RF+/Echo-, RF+/Echo+). Multivariable-adjusted associations between RF/Echo subgroups and physical performance metrics from 6-minute walk and treadmill exercise testing were assessed.<br /><b>Results</b><br />Prevalence was: 35.3% for RF-/Echo-, 4.7% for RF-/Echo+, 39.3% for RF+/Echo- and 20.6% for RF+/Echo+. We observed large diversity in echocardiographic profiles in the Echo+ group. Participants with RF-/Echo+ (18.6% of Echo+) predominantly had echocardiographic abnormalities other than left ventricular (LV) diastolic dysfunction, hypertrophy and reduced ejection fraction, while their physical performance was similar to RF-/Echo-. In contrast, participants with RF+/Echo+ mostly presented LV hypertrophy or dysfunction, features that related to lower 6-minute walking distance and lower exercise capacity.<br /><b>Conclusions</b><br />Subclinical echocardiographic abnormalities suggest HF pathogenesis, but the presence of HF risk factors and type of echo abnormality should be considered to distinguish adverse from benign adaptation and stratify HF risk.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 26 Apr 2023; epub ahead of print</small></div>

<div><h4>Modification of a transvalvular microaxial flow pump for instantaneous determination of native cardiac output and volume.</h4><i>Aslam MI, Gruslova AB, Almomani A, Nolen D, ... Valvano JW, Feldman MD</i><br /><b>Background</b><br />The current Impella CP pump used for mechanical circulatory support (MCS) in patients with cardiogenic shock (CS) cannot assess native cardiac output (CO) and left ventricular (LV) volumes. This data is valuable in facilitating device management and weaning. Admittance technology allows for accurate assessment of cardiac chamber volumes.<br /><b>Objectives</b><br />This study tested the ability to engineer admittance electrodes onto an existing Impella CP pump to assess total and native CO in an instantaneous manner, as well as LV chamber volumes.<br /><b>Methods</b><br />Impella CP pumps were fitted with four admittance electrodes and placed in the LV of adult swine (n=9) subjected to three different hemodynamic conditions including Impella CP speed adjustments, administration of escalating doses of dobutamine, and microsphere injections into the left main artery to result in cardiac injury. CO by admittance electrodes was calculated from LV volumes and heart rate. In addition, CO was calculated in each instance via thermodilution, continuous CO (CCO) measurement, Fick\'s principle and aortic velocity-time integral (VTI) by echocardiography.<br /><b>Results</b><br />Modified Impella CP pumps were placed in swine LV successfully. CO as determined by admittance electrodes was similar by trend with other methods of CO assessment, corrected for pump speed to calculate native CO, and calculated LV chamber volumes trended as expected in each experimental protocol.<br /><b>Conclusions</b><br />We report for the first time that an Impella CP pump can be fitted with admittance electrodes and used to determine total and native CO in various hemodynamic situations.<br /><b>Condensed abstract</b><br />Transvalvular mechanical circulatory support (MCS) devices such as the Impella CP do not have the ability to provide real-time information on native cardiac output (CO) and left ventricular (LV) volumes. This information is critical in device management and weaning in patients with cardiogenic shock (CS). We demonstrate for the first time, an Impella CP pump coupled with admittance electrodes are able to determine native CO, and left ventricle (LV) chamber volumes in multiple different hemodynamic situations such as Impella pump speed adjustments, escalating dobutamine administration, and cardiac injury from microsphere injection.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 25 Apr 2023; epub ahead of print</small></div>

<div><h4>Organ Donation and Transplantation among Non-US Citizens: Opportunities to Improve Global Equity in Heart Transplantation.</h4><i>DeFilippis EM, Batra J, Blumer V, Peoples IA, ... Sauer AJ, Ibrahim NE</i><br /><b>Background</b><br />Non-US citizens/non-US residents (NCNR) are a unique and growing population. Patterns of heart donation and heart transplantation (HT) within this subgroup have not been fully described. The purpose of this study was to evaluate the use of organs from NCNR donors and the characteristics and outcomes of NCNR HT recipients.<br /><b>Methods</b><br />All adult donors whose hearts were recovered for HT and all primary adult HT recipients from 2013-2020 were identified using the United Network for Organ Sharing (UNOS). Donors and recipients were categorized as citizens, residents, or NCNR. Non-citizens/non-residents were further categorized by reason for travel to the US. Outcomes included mortality, infection, and rejection at 1-year post-transplantation.<br /><b>Results</b><br />NCNR accounted for 0.4% (n = 77) of heart donors. Most NCNR donors identified as Hispanic (61%), were predominately recovered from the South and Southwest US and were less likely to express written documentation to be a donor compared to citizens and residents. NCNR accounted for 0.7% (n = 147) of all HT recipients. The majority identified as non-Hispanic White individuals (57.1%). Compared to citizens and residents, NCNR recipients appeared sicker as evidenced by higher IABP utilization before HT and higher priority UNOS status. 63% of NCNR recipients traveled to the US for HT, predominately from Kuwait (29.9%) and Saudi Arabia (20%). At 1-year post-transplant, there were no differences in mortality, infection, or rejection between groups.<br /><b>Conclusions</b><br />A growing subgroup of NCNR travel from countries with low HT rates to the US for HT. This highlights the need for strategies to improve equitable access to HT domestically and abroad.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 21 Apr 2023; epub ahead of print</small></div>

<div><h4>Iron Deficiency in Heart Failure: A Scientific Statement from the Heart Failure Society of America.</h4><i>Beavers CJ, Ambrosy AP, Butler J, Davidson BT, ... Mentz RJ, Lewis GD</i><br /><AbstractText>Iron deficiency is present in approximately 50% of patients with symptomatic heart failure and is independently associated with worse functional capacity, lower quality of life and increased mortality. The purpose of this document is to summarize current knowledge of how iron deficiency is defined in heart failure, its epidemiology and pathophysiology, as well as pharmacological considerations for repletion strategies. This document also summarizes the rapidly expanding array of clinical trial evidence informing when, how, and in whom to consider iron repletion.</AbstractText><br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>J Card Fail: 19 Apr 2023; epub ahead of print</small></div>

<div><h4>Natriuretic Peptides: Role in the Diagnosis and Management of Heart Failure: A Scientific Statement From the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society.</h4><i>Tsutsui H, Albert NM, Coats AJS, Anker SD, ... Yamamoto K, Yoshimura M</i><br /><AbstractText>Natriuretic peptides, brain (B-type) natriuretic peptide (BNP) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) are globally and most often used for the diagnosis of heart failure (HF). In addition, they can have an important complementary role in the risk stratification of its prognosis. Since the development of angiotensin receptor neprilysin inhibitors (ARNIs), the use of natriuretic peptides as therapeutic agents has grown in importance. The present document is the result of the Trilateral Cooperation Project among the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America and the Japanese Heart Failure Society. It represents an expert consensus that aims to provide a comprehensive, up-to-date perspective on natriuretic peptides in the diagnosis and management of HF, with a focus on the following main issues: (1) history and basic research: discovery, production and cardiovascular protection; (2) diagnostic and prognostic biomarkers: acute HF, chronic HF, inclusion/endpoint in clinical trials, and natriuretic peptides-guided therapy; (3) therapeutic use: nesiritide (BNP), carperitide (ANP) and ARNIs; and (4) gaps in knowledge and future directions.</AbstractText><br /><br />Copyright © 2023 Elsevier Inc., European Society of Cardiology. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Card Fail: 17 Apr 2023; epub ahead of print</small></div>

<div><h4>The First Dedicated Comprehensive Heart Failure Program in the US: the Division of Circulatory Physiology at Columbia Presbyterian (1992-2004).</h4><i>Packer M</i><br /><AbstractText>The first dedicated multidisciplinary heart failure program in the US was founded as the Division of Circulatory Physiology at the Columbia University College of Physicians & Surgeons in 1992. The Division was administratively and financially independent of the Division of Cardiology and grew to 24 faculty members at its peak. Its administrative innovations included (1) a comprehensive full-integrated service line, with two differentiated clinical teams, one devoted to drug therapy and the other to heart transplantation and ventricular assist devices; (2) a nurse specialist/physician assistant-led clinical service; and (3) a financial structure independent of (and not supported by) other cardiovascular medical or surgical services. The Division had three overarching missions: (1) to promote a unique career development path for each faculty member to be linked to recognition in a specific area of heart failure expertise; (2) to change the trajectory and enhance the richness of intellectual discourse in the discipline of heart failure, so as to foster an understanding of fundamental mechanisms and to develop new therapeutics; and (3) to provide optimal medical care to patients and to promote the ability of other physicians to provide optimal care. The major research achievements of the Division included: (1) the development of beta-blockers for heart failure, from initial hemodynamic assessments to proof-of-concept studies to large-scale international trials; (2) the development and definitive assessment of flosequinan, amlodipine and endothelin antagonists; (3) initial clinical trials and concerns with nesiritide; (4) large-scale trials evaluating dosing of angiotensin converting-enzyme inhibitors and the efficacy and safety of neprilysin inhibition; (5) identification of key mechanisms in heart failure, including neurohormonal activation, microcirculatory endothelial dysfunction, deficiencies in peripheral vasodilator pathways, noncardiac factors in driving dyspnea, and the first identification of subphenotypes of heart failure and a preserved ejection fraction; (6) the development of a volumetric approach to the assessment of myocardial shortening; (7) conceptualization and early studies of cardiac contractility modulation as a treatment for heart failure; (8) novel approaches to the identification of cardiac allograft rejection and new therapeutics to prevent allograft vasculopathy; and (9) demonstration of the effect of left ventricular assist devices to induce reverse remodeling, and the first randomized trial showing a survival benefit with ventricular assist devices. Above all, the Division served as an exceptional incubator for a generation of leaders in the field of heart failure.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 17 Apr 2023; epub ahead of print</small></div>

<div><h4>Safety and Efficacy of Istaroxime 1.0 and 1.5 µg/kg/min for Patients with Pre Cardiogenic Shock.</h4><i>Metra M, Chioncel O, Davison B, Filippatos G, ... Simonson S, Cotter G</i><br /><b>Introduction</b><br />Istaroxime was shown in a small study to increase systolic blood pressure (SBP) in patients with pre-cardiogenic shock (CS) due to acute heart failure (AHF).<br /><b>Objectives</b><br />In the current analysis we describe the effects of two doses of istaroxime 1.0 (Ista-1) and 1.5 µg/kg/min (Ista-1.5).<br /><b>Methods</b><br />The target dose of istaroxime, administered in a double-blind placebo-controlled fashion, was 1.5 µg/kg/min in the first cohort (n=24) and was reduced to 1.0 µg/kg/min in subsequent patients (n =36).<br /><b>Results</b><br />Ista-1 was associated with numerically larger effects on SBP area under the curve with a 93.6% relative increase from baseline during the first 6 hours with Ista-1 vs. 39.5% for Ista-1.5, and with a 49.4% and 24.3% relative increase, respectively, at 24 hours. Compared to placebo, Ista-1.5 had more worsening HF events to day 5 and fewer days alive out of hospital (DAOH) through day 30. Ista-1 had no worsening HF events and DAOH to day 30 were significantly increased. Effects on echocardiographic measures were similar although decrease in left ventricular end systolic and diastolic volumes was numerically larger in the Ista-1. Ista-1, but not Ista-1.5, had numerically smaller creatinine increase and larger decrease in natriuretic peptides as compared to placebo. There were 5 serious adverse events in Ista-1.5 (4 of which cardiac) but only 1 in Ista-1.<br /><b>Conclusions</b><br />In patients with pre-CS due to AHF, istaroxime 1.0 µg/kg/min induced beneficial effects on SBP, and DAOH. Clinical benefits appear to be reached at doses less than 1.5 ug/kg/min.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 17 Apr 2023; epub ahead of print</small></div>

<div><h4>Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction: SATELLITE Trial Results.</h4><i>Lam CSP, Lund LH, Shah SJ, Voors AA, ... Gan LM, Gabrielsen A</i><br /><b>Background</b><br />Inflammation is a key driver of heart failure (HF) with preserved left ventricular ejection fraction (LVEF). AZD4831 inhibits extracellular myeloperoxidase, reduces inflammation and improves microvascular function in preclinical disease models.<br /><b>Methods</b><br />In this double-blind phase 2a study (SATELLITE; NCT03756285), patients with symptomatic HF, LVEF ≥40%, and elevated B-type natriuretic peptides were randomized 2:1 to once-daily oral AZD4831 5 mg or placebo for 90 days. We aimed to assess target engagement (primary endpoint: myeloperoxidase specific activity) and safety of AZD4831.<br /><b>Results</b><br />Due to COVID-19, the study was terminated early after randomizing 41 patients (median age, 74.0 years; 53.7% male). Myeloperoxidase activity was reduced by >50% from baseline to day 30 and 90 in the AZD4831 group, with a placebo-adjusted reduction of 75% (95% confidence interval: 48, 88; nominal P <0.001). No improvements were noted in secondary/exploratory endpoints, apart from a trend in Kansas City Cardiomyopathy Questionnaire overall summary score. No deaths or treatment-related serious adverse events occurred. AZD4831 treatment-related adverse events were generalized maculopapular rash, pruritus and diarrhoea (all n=1).<br /><b>Conclusions</b><br />AZD4831 inhibited myeloperoxidase and was well tolerated in patients with HF and LVEF ≥40%. Efficacy findings were exploratory due to early termination but warrant further clinical investigation of AZD4831.<br /><b>Lay summary</b><br />Few treatments are available for patients with the forms of heart failure known as \'heart failure with preserved or mildly reduced ejection fraction\'. Current treatments do not target inflammation, which may play an important role in this condition. We tested a new drug called AZD4831 (mitiperstat), which reduces inflammation by inhibiting the enzyme myeloperoxidase. Among the 41 patients in our clinical trial, AZD4831 had a good safety profile and inhibited myeloperoxidase by the expected amount. Results mean we can conduct further trials to see whether AZD4831 reduces the symptoms of heart failure and improves patients\' ability to take physical exercise.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 16 Apr 2023; epub ahead of print</small></div>

<div><h4>Sex and Race Differences in Cardiac Sarcoidosis Presentation, Treatment, and Outcomes.</h4><i>Duvall C, Pavlovic N, Rosen NS, Wand AL, ... Chrispin J, Gilotra NA</i><br /><b>Background</b><br />Though sex and race-based patterns have been described in extracardiac organ involvement of sarcoidosis, cardiac sarcoidosis (CS) specific studies are lacking.<br /><b>Methods</b><br />We studied CS presentation, treatment, and outcomes based on sex and race among a tertiary center cohort. Multivariable adjusted Cox proportional hazards and survival analyses were performed for primary composite outcome (left ventricular assist device, heart transplantation, all-cause death) and secondary outcomes ventricular arrhythmia (VA) and all-cause death.<br /><b>Results</b><br />We identified 252 CS patients (108 female, 109 Black). At CS presentation, females vs. males (p=0.001) and Black vs. White individuals (p=0.001) more frequently had symptomatic heart failure (HF), with HF most common in Black females (ANOVA p <0.001). Treatment differences included more corticosteroid use (90% vs 79%, p=0.020), higher 1-year prednisone dose (13 vs 10 mg, p=0.003) and less frequent early steroid-sparing agent use in males (29% vs 40%, p=0.05). Black participants more frequently received a steroid-sparing agent (75% vs 60%, p=0.023). Composite outcome free survival did not differ by sex or race. Male sex had an adjusted hazard ratio of 2.34 (95% CI 1.13, 4.80; p=0.021) for VA.<br /><b>Conclusion</b><br />CS course may differ by sex and race and contribute to distinct clinical CS phenotypes.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 14 Apr 2023; epub ahead of print</small></div>

<div><h4>Oral Sodium to Preserve Renal Efficiency in Acute Heart Failure: A Randomized, Placebo-Controlled, Double-Blinded Study.</h4><i>Montgomery RA, Mauch J, Sankar P, Martyn T, ... Estep JD, Wilson Tang WH</i><br /><b>Background</b><br />Evidence for modulating sodium chloride (NaCl) intake of patients hospitalized with acute heart failure (AHF) is inconclusive. Salt restriction may not benefit while hypertonic saline may aid diuresis.<br /><b>Objectives</b><br />To compare the safety and efficacy of oral NaCl during intravenous (IV) diuretic therapy on renal function and weight.<br /><b>Methods</b><br />70 hospitalized patients with AHF being treated with IV furosemide infusion were consented to randomly receive 2 grams of oral NaCl or placebo three times a day in double-blind manner during IV diuresis. Treatment efficacy (bivariate primary endpoint of change in serum creatinine and change in weight) was measured at 96-hours and adverse safety events were tracked over 90-days.<br /><b>Results</b><br />65 patients (34 NaCl, 31 placebo) were included for analysis after 5 withdrew. A median of 13 grams of NaCl was given compared to placebo. At 96-hours, there was no significant difference between treatment groups with respect to the primary endpoint (p=0.33), however the trial was underpowered with greater than expected standard deviation in weight change. Mean change in creatinine and weight was 0.15±0.44 mg/dl and 4.6±4.2 kg in the placebo group, as compared with 0.04±0.40 mg/dl and 4.0±4.3 kg in the NaCl group (p=0.30 & 0.57, respectively). Across efficacy and safety endpoints, we observed no significant difference between the two groups other than changes in serum sodium (-2.6±2.7 in placebo & -0.3±3.3 mEq/l in NaCl group; p<0.001) and serum blood urea nitrogen (11±15 in placebo & 3.1±13 mEq/l in NaCl group; p=0.025).<br /><b>Conclusions</b><br />In this single-center study, liberal versus restrictive oral sodium chloride intake strategies did not impact the safety and efficacy of intravenous diuretic therapy in AHF. (ClinicalTrials.gov registration NCT04334668).<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 10 Apr 2023; epub ahead of print</small></div>

<div><h4>Recruitment Strategies of a Decentralized Randomized Placebo Controlled Clinical Trial: The Canagliflozin Impact on Health Status, Quality of Life and Functional Status in Heart Failure (CHIEF-HF) Trial.</h4><i>Nassif M, Birmingham MC, Lanfear DE, Golbus JR, ... Harrison MC, Spertus JA</i><br /><b>Background</b><br />There has been growing Interest in patient-centered clinical trials using mobile technologies to reduce the need for in-person visits. The CHIEF-HF trial was designed as a double-blind, randomized, fully decentralized clinical trial (DCT) that identified, consented, treated, and followed participants without any in-person visits. Patient-reported questionnaires were the primary outcome, which were collected by a mobile application. To inform future DCTs, we sought to describe the strategies used in successful trial recruitment.<br /><b>Methods</b><br />This paper describes the operational structure and novel strategies employed in a completely DCT by summarizing the recruitment, enrollment, engagement, retention, and follow-up processes used in the execution of the trial at 18 centers.<br /><b>Results</b><br />A total of 18 sites contacted 130,832 potential participants, of which 2,572 (2.0%) opened a hyperlink to the study website, completed a brief survey, and agreed to be contacted for potential inclusion. Of these, 1,333 were eligible and 658 consented with 182 screen-failures, primarily due to baseline Kansas City Cardiomyopathy Questionnaire scores not meeting inclusion criteria, resulting in 476 participants being enrolled (18.5%). There was significant site-level variation in the number of patients invited (median = 2,976; range 73-46,920) and in those agreeing to be contacted (median = 2.4%; range 0.05% - 16.4%). At the highest enrolling site, patients contacted by electronic medical record portal messaging were more likely to successfully opt-into the study than those contacted by email alone (7.8% vs 4.4%).<br /><b>Conclusions</b><br />CHIEF-HF used a novel design and operational structure to test the efficacy of a therapeutic treatment but marked variability across sites and strategies in recruiting participants was observed. While this approach may be advantageous for clinical research across a broader range of therapeutic areas, further optimizing recruitment efforts is warranted.<br /><b>Registration</b><br />NCT04252287: https://clinicaltrials.gov/ct2/show/NCT04252287.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 09 Apr 2023; epub ahead of print</small></div>

<div><h4>The Effect of Sacubitril/Valsartan on Left Ventricular Myocardial Deformation in Heart Failure with Preserved Ejection Fraction (PARAMOUNT trial).</h4><i>Biering-Sørensen T, Lassen MCH, Shah A, Claggett B, ... Solomon SD, PARAMOUNT Investigators</i><br /><b>Background</b><br />Global longitudinal (GLS) and global circumferential strain (GCS) have been shown to be impaired in HFpEF.<br /><b>Objectives</b><br />To assess whether treating HFpEF patients with sacubitril/valsartan would significantly improve GLS and GCS compared to valsartan alone.<br /><b>Methods</b><br />PARAMOUNT was a phase 2, randomized, parallel-group, double-blind multicenter trial in 301 patients with New York Heart Association (NYHA) class II-III HF, LVEF ≥45%, and NT-proBNP ≥400 pg/mL. Participants were randomly assigned (1:1) to sacubitril/valsartan titrated to 200 mg twice daily or valsartan titrated to 160 mg twice daily for 36 weeks. We assessed change in GLS and GCS from baseline to 36 weeks, adjusting for baseline value, in patients with sufficient imaging quality for 2D speckle tracking analysis at both timepoints (n=60 sacubitril/valsartan, n=75 valsartan only).<br /><b>Results</b><br />GCS was significantly improved at 36 weeks in the sacubitril/valsartan group when compared with the valsartan group (Δ4.42%, 95%CI [0.67-8.17], p=0.021), with no significant difference observed in GLS (Δ0.25%, 95%CI [-1.19-1.70], p=0.73). Patients with a history of HF hospitalization had a differentially greater improvement in GCS when treated with sacubitril/valsartan.<br /><b>Conclusions</b><br />In patients with HFpEF, sacubitril/valsartan improved GCS but not GLS when compared to valsartan during a 36 weeks period. This trial is registered at ClinicalTrials.gov, NCT00887588.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 07 Apr 2023; epub ahead of print</small></div>

<div><h4>Cardiac Regenerative Therapy Using Human Pluripotent Stem Cells for Heart Failure: A State-of-the-Art Review.</h4><i>Kishino Y, Tohyama S, Morita Y, Soma Y, ... Kanazawa H, Fukuda K</i><br /><AbstractText>Heart transplantation (HT) is the only definitive treatment available for patients with end-stage heart failure who are refractory to medical and device therapies. However, HT as a therapeutic option, is limited by a significant shortage of donors. To overcome this shortage, regenerative medicine using human pluripotent stem cells (hPSCs), such as human embryonic stem cells and human-induced pluripotent stem cells (hiPSCs), has been considered an alternative to HT. Several issues, including the methods of large-scale culture and production of hPSCs and cardiomyocytes, the prevention of tumorigenesis secondary to contamination of undifferentiated stem cells and non-cardiomyocytes, and the establishment of an effective transplantation strategy in large-animal models, need to be addressed to fulfill this unmet need. Although post-transplantation arrhythmia and immune rejection remain problems, the ongoing rapid technological advances in hPSC research have been directed toward the clinical application of this technology. Cell therapy using hPSC-derived cardiomyocytes is expected to serve as an integral component of realistic medicine in the near future and is being potentially viewed as a treatment that would revolutionize the management of patients with severe heart failure.</AbstractText><br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>J Card Fail: 01 Apr 2023; 29:503-513</small></div>

<div><h4>PROMIS® Physical, Mental and Social Health Outcomes Improve from Before to Early After LVAD Implant: Findings from the Mechanical Circulatory Support: Measures of Adjustment and Quality of Life (MCS A-QOL) Study.</h4><i>Hahn EA, Allen LA, Lee CS, Denfeld QE, ... Vela AM, Grady KL</i><br /><AbstractText>Study participants (n=272) completed 12 Patient-Reported Outcomes Measurement Information System (PROMIS®) physical, mental and social health measures (questionnaires) prior to implantation of a left ventricular assist device (LVAD) and again at 3 and 6 months post-implant. All but one PROMIS measure demonstrated significant improvement from pre-implant to 3 months; there was little change between 3 and 6 months. Because PROMIS measures were developed in the general population, patients with an LVAD, their caregivers and their clinicians can interpret the meaning of PROMIS scores in relation to the general population, helping them to monitor a return to normalcy in everyday life.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 31 Mar 2023; epub ahead of print</small></div>

<div><h4>Pharmacist- and Nurse-Led Medical Optimization in Heart Failure: A Systematic Review and Meta-Analysis.</h4><i>Zheng J, Mednick T, Heidenreich PA, Sandhu AT</i><br /><b>Background</b><br />Traditional approaches to guideline-directed medical therapy (GDMT) management often lead to delayed initiation and titration of therapies in heart failure. This study sought to characterize alternative models of care involving non-physician provider-led GDMT interventions and their associations with therapy utilization and clinical outcomes.<br /><b>Methods</b><br />We performed a systematic review and meta-analysis of randomized controlled trials (RCT) and observational studies comparing non-physician provider-led GDMT initiation and/or uptitration interventions versus usual physician care (PROSPERO ID: CRD42022334661). We queried PubMed, Embase, the Cochrane Library, and the World Health Organization International Clinical Trial Registry Platform for peer-reviewed studies from database inception to July 31, 2022. In the meta-analysis, we used RCT data only and leveraged random-effects models to estimate pooled outcomes. Primary outcomes were GDMT initiation and titration to target doses by therapeutic class. Secondary outcomes included all-cause mortality and HF hospitalizations.<br /><b>Results</b><br />33 studies were reviewed, of which 17 (52%) were randomized controlled trials with median follow-up of 6 months. 14 (82%) trials evaluated nurse interventions, while the remainder assessed pharmacist interventions. The primary analysis pooled data from 16 RCTs, which enrolled 5,268 patients. Pooled risk ratios (RR) for RASI and BB initiation were 2.09 (95% CI 1.05-4.16; I<sup>2</sup>=68%) and 1.91 (95% CI 1.35-2.70; I<sup>2</sup>=37%), respectively. Outcomes were similar for uptitration of RASI (RR 1.99, 95% CI 1.24-3.20; I<sup>2</sup>=77%) and BB (RR 2.22, 95% CI 1.29-3.83; I<sup>2</sup>=66%). No association was found with MRA initiation (RR 1.01, 95% CI 0.47-2.19). There were lower rates of mortality (RR 0.82, 95% CI 0.67-1.04; I<sup>2</sup>=12%) and HF hospitalization (RR 0.80, 95% CI 0.63-1.01; I<sup>2</sup>=25%) across intervention arms, but these differences were small and not statistically significant. Prediction intervals were wide due to moderate-to-high heterogeneity across trial populations and interventions. Subgroup analyses by provider type did not show significant effect modification.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Pharmacist- and nurse-led interventions for GDMT initiation and/or uptitration improved guideline concordance. Further research evaluating newer therapies and titration strategies integrated with pharmacist- and/or nurse-based care may be valuable.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 31 Mar 2023; epub ahead of print</small></div>

<div><h4>Decoupling of Hemodynamics and Congestive Symptoms in Obese Heart Failure Patients.</h4><i>Keck C, Gregoski M, Litwin S, Borlaug BA, ... Tedford RJ, Houston BA</i><br /><b>Background</b><br />Prior studies indicate significant physiologic differences between obese and non-obese heart failure (HF) patients, but none have evaluated differences in hemodynamic patterns in these patient populations during treatment for acute decompensated HF (ADHF).<br /><b>Objectives</b><br />In this study, we assessed differences in hemodynamic trends between obese and non-obese patients during treatment for ADHF.<br /><b>Methods</b><br />Obese (BMI >30, n=63) and non-obese (BMI <25, n=69) patients with ADHF in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) study who had pulmonary artery catheterization data available through the duration of treatment were evaluated. Hemodynamics were analyzed at baseline and optimal day. Changes in BNP, weight, creatinine, BUN, 6MWT, orthopnea and dyspnea scores were assessed.<br /><b>Results</b><br />Despite similar baseline hemodynamics, obese patients had significantly less absolute and relative pulmonary arterial wedge pressure (PAWP) reduction (-16 ± 28 versus -32 ± 29%, p = 0.03) during treatment. Obese patients also had higher PAWP (19.9 + 8 versus 15.5 + 6.8 mmHg, p=0.01) and PA pressures at optimization compared with non-obese patients. Obese and non-obese patients had similar relative improvements in weight, BNP, six minute walk test distance, dyspnea and orthopnea scores, and similar changes in creatinine and BUN.<br /><b>Conclusions</b><br />Obese patients treated for ADHF display less reduction in invasively measured left heart filling pressures, despite similar improvements in symptoms, weight loss, and noninvasive surrogates of congestion. Our findings suggest a degree of decoupling between left heart filling pressures and congestive symptoms in obese patients undergoing treatment for ADHF.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 22 Mar 2023; epub ahead of print</small></div>

<div><h4>Beyond Stage C: Considerations in the Management of Patients with Heart Failure Progression and Gaps in Evidence.</h4><i>Carroll AM, Farr M, Russell SD, Schlendorf KH, ... Patel CB, DeVore AD</i><br /><AbstractText>Despite treatment with contemporary medical therapies for chronic heart failure (HF), there has been an increase in the prevalence of patients progressing to more advanced disease. Patients progressing to and living at the interface of severe Stage C and Stage D HF are underrepresented in clinical trials, and there is a lack of high-quality evidence to guide clinical decision making. For patients with a severe HF phenotype, the medical therapies used for patients with a less advanced stage of illness are often no longer tolerated nor provide adequate clinical stability. The limited data on these patients highlights the need to increase formal research characterizing this high-risk population. This review summarizes existing clinical trial data on and incorporates our considerations for approaches to the medical management of patients advanced \"beyond Stage C\" HF.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 21 Mar 2023; epub ahead of print</small></div>

<div><h4>Transcatheter Left Ventricular Restoration in patients with Heart Failure.</h4><i>Hamid N, Jorde UP, Reisman M, Latib A, ... Leon MB, Burkhoff D</i><br /><b>Background</b><br />Left ventricular (LV) volume reshaping reduces myocardial wall stress and may induce reverse remodeling in subjects with heart failure with reduced ejection fraction (HFrEF). The AccuCinch® Transcatheter Left Ventricular Restoration (TLVR) system consists of a series of anchors connected by a cable implanted along the LV base that is cinched to reduce basal free wall radius. We evaluated the echocardiographic and clinical outcomes following TLVR.<br /><b>Methods</b><br />We analyzed 51 HFrEF subjects with LVEF between 20 and 40%, ≤2+ mitral regurgitation (MR) treated with optimal medical therapy, who subsequently underwent TLVR. Serial echocardiograms, Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, and 6-minute walk test distances (6MWD) were measured at baseline through 12 months. Primary analysis endpoint was change in end-diastolic volume (EDV) at 12 months compared to baseline.<br /><b>Results</b><br />Patients (n=51) were predominantly male (86%) with mean age 56.3±13.1 years. Fluoroscopy showed LV free wall radius decreased by a median of 9.2 mm amounting to a 29.6% reduction of free wall arc length. At 12 months, LVEDV decreased by 33.6±34.8 ml (p<0.01), with comparable reductions of LV end-systolic volume (ESV). These were associated with significant improvements of overall KCCQ score (16.4±18.7 points, p<0.01) and 6MWD (45.9±83.9 m, p<0.01). There were no periprocedural deaths; through 1-year follow-up, 1 subject died (day 280) and one subjects received an LVAD (day 13).<br /><b>Conclusion</b><br />In HFrEF patients without significant MR receiving optimal medical therapy, the AccuCinch® System resulted in LV volume reductions, improved quality of life and exercise endurance. A randomized trial is ongoing (NCT04331769).<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 21 Mar 2023; epub ahead of print</small></div>

<div><h4>Person with Heart Failure and Care Partner Dyads: Current Knowledge, Challenges, and Future Directions: State-of-the-Art Review.</h4><i>Bidwell JT, Conway C, Babicheva V, Lee CS</i><br /><AbstractText>Over the past decade, there has been substantial growth in heart failure (HF) research that focuses on persons with HF and their care partners (family members or other close friends that provide unpaid support) as an interdependent team, or \"care dyad.\" In this state-of-the-art review, we use a dyadic lens to identify and summarize current research on HF care dyads, from qualitative studies, to non-experimental quantitative studies, to randomized-controlled trials. Although much work has been done, this literature is younger and less well-developed than care dyad literatures from other conditions (e.g., cancer, Alzheimer\'s disease). We discuss the substantial challenges and limitations in this body of work, with an eye towards addressing common issues that impact rigor. We also look towards future directions, and discuss the promise dyadic research holds for improving patient, care partner, and relationship health.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 21 Mar 2023; epub ahead of print</small></div>

<div><h4>Getting into Light Exercise (GENTLE-HF) for Patients with Heart Failure: The Design and Methodology of a Live-Video Group Exercise Study.</h4><i>Howie-Esquivel J, Metzger M, Malin SK, Mazimba S, ... Toledo G, Park L</i><br /><b>Introduction</b><br />Newer therapies have increased heart failure (HF) survival rates, but these therapies are rarely curative. The consequence of increased longevity is the likelihood that patients with HF will experience higher symptom burden over time. Exercise, such as cardiac rehabilitation programs, can palliate symptom burden, but numerous barriers prevent exercise participation and adherence. Small pilot studies indicate short-term beneficial effects of gentle forms of exercise, such as yoga to address symptom burden and accommodate co-morbidities. Long-term symptom benefit and adherence to yoga are currently not known. Therefore, a novel a home-based gentle stretching intervention that addresses issues of exercise access and adherence is described.<br /><b>Purpose</b><br />The purpose of this paper is to describe the background, design and study methodology of the Getting Into Light Exercise for HF (GENTLE-HF) randomized controlled trial. Gentle-HF will test a gentle stretching and education intervention compared to an education control group on: 1) Symptom burden (dyspnea, exercise, activity adherence, depression and anxiety) and quality of life. As an exploratory aim we also will determine whether rurality moderates the relationships among exercise participation and symptom burden as a measure of health equity.<br /><b>Methods</b><br />We designed a randomized controlled trial study (N=234) with two arms: A gentle stretching intervention arm with HF education and an HF education only control. Participants will be recruited from US cardiology clinics in the Mid-Atlantic and the San Francisco Bay Area. This recruitment strategy will include individuals from urban, suburban and rural areas and individuals that have diverse racial and ethnic backgrounds. All participants will be provided with an iPad set up to access HF educational topics and the intervention arm will have both educational and gentle stretching class links. Both arms will access the HF health education icons on their iPads weekly that correspond to the 6 months (26 weeks) of study participation. Symptom burden (dyspnea, fatigue, exercise intolerance, depression, anxiety) and QOL will be measured at study start and completion. Study adherence will be measured using attendance rates and number of class minutes attended.<br /><b>Results</b><br />The GENTLE-HF study is a randomized study that will test the effect of a home-based, video-conference delivered gentle stretching and HF education intervention designed for patients with HF. The findings will inform whether gentle stretching can decrease symptom burden and potentially provide access to symptom palliation for a diverse population of patients with HF.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 20 Mar 2023; epub ahead of print</small></div>

<div><h4>Treatment adherence in a randomised controlled trial of pirfenidone in HFpEF: determinants and impact on efficacy.</h4><i>Soltani F, Lewis GA, Rosala-Hallas A, Dodd S, ... McDonagh T, Miller CA</i><br /><b>Aims</b><br />Medication adherence in patients with heart failure with preserved ejection fraction (HFpEF) is unclear. This study sought to evaluate treatment adherence in the Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction (PIROUETTE) trial.<br /><b>Methods and results</b><br />Adherence was evaluated through pill counts and diary cards. Univariable and multivariable regression models were used to assess the relationship between adherence and baseline characteristics. Instrumental variable regression was used to estimate the causal effect of pirfenidone treatment duration on myocardial fibrosis. Complete adherence data was available in 54 of 80 participants completing the trial. Mean adherence with study medication was 94.7% and 96.9% in the pirfenidone and placebo groups respectively. Each additional day of treatment with pirfenidone resulted in a significant decrease in myocardial extracellular volume (-0.004%; 95% confidence interval: -0.007% to -0.001%; p=0.007). Associations with adherence included older age, higher symptom burden, lower body weight and smaller right ventricular size.<br /><b>Conclusion</b><br />Adherence with study medication in the PIROUETTE trial was very high among patients for whom complete adherence data was available. Importantly, each additional day of treatment reduced myocardial fibrosis. Potential predictors of adherence were identified. Implementation of improved methods for assessing adherence is required.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 13 Mar 2023; epub ahead of print</small></div>

<div><h4>Multidisciplinary Care in Heart Failure Services.</h4><i>Sokos G, Kido K, Panjrath G, Benton E, ... Korous S, Guglin M</i><br /><AbstractText>The American College of Cardiology/American Heart Association /Heart Failure Society of American 2022 guidelines for heart failure (HF) recommend a multidisciplinary team approach for patients with HF. The multidisciplinary HF team-based approach reduces the hospitalization rate for HF and healthcare costs and improves adherence to self-care and utilization of GDMT. This manuscript proposes the optimal multidisciplinary team structure and each team member\'s delineated role to achieve institutional goals and metrics for HF care. The proposed HF-specific multidisciplinary team comprises cardiologists, surgeons, advanced practice providers, clinical pharmacists, specialty nurses, dieticians, physical therapists, psychologists, social workers, immunologists, and palliative care clinicians. A standardized multidisciplinary HF team-based approach should be incorporated to optimize the structure, minimize redundancy of clinical responsibilities among team members, and improve clinical outcomes and patient satisfaction in their HF care.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 13 Mar 2023; epub ahead of print</small></div>

<div><h4>Exertional Cardiac and Pulmonary Vascular Hemodynamics Among Patients with Heart Failure with Reduced Ejection Fraction.</h4><i>Edward JA, Parker H, Stöhr EJ, McDonnell BJ, ... Lawley JS, Cornwell WK</i><br /><b>Background</b><br />Exertional dyspnea is a cardinal manifestation of heart failure with reduced ejection fraction (HFrEF) but quantitative data regarding exertional hemodynamics are lacking.<br /><b>Objectives</b><br />Characterize exertional cardiopulmonary hemodynamics in patients with HFrEF.<br /><b>Methods</b><br />Thirty-five HFrEF patients (59±12 years, 30 males) completed invasive cardiopulmonary exercise testing (CPET). Data were collected at rest, submaximal exercise and peak effort on upright cycle ergometry. Cardiovascular and pulmonary vascular hemodynamics were recorded. Fick cardiac output (Qc) was determined. Hemodynamic predictors of peak oxygen uptake (VO<sub>2</sub>) were identified.<br /><b>Results</b><br />Left ventricular ejection fraction and cardiac index were 23±8% and 2.9±1.1 L/min/m<sup>2</sup>, respectively. PeakVO<sub>2</sub> was 11.8±3.3 ml/kg/min and ventilatory efficiency slope was 53±13. Right atrial pressure increased from rest to peak exercise (4±5 v. 7±6mmHg,). Mean pulmonary arterial pressure increased from rest to peak exercise (27±13 v. 38±14mmHg). Pulmonary artery pulsatility index increased from rest to peak exercise, while pulmonary arterial capacitance and pulmonary vascular resistance declined.<br /><b>Conclusions</b><br />HFrEF patients suffer from marked increases in filling pressures during exercise. These findings provide new insight into cardiopulmonary abnormalities contributing to impairments in exercise capacity in this population.<br /><b>Clinical trial registration</b><br />clinicaltrials.gov identifier: NCT03078972 LAY SUMMARY: Exertional dyspnea is a cardinal manifestation of heart failure with reduced ejection fraction (HFrEF). In this analysis, resting and exertional hemodynamics are analyzed from a contemporary cohort of patients with HFrEF (59±12 years, left ventricular ejection fraction 23±8%) during invasive cardiopulmonary exercise testing with upright cycle ergometry. During submaximal and peak exercise, large increases in left- and right-sided filling pressures were demonstrated. Maximal oxygen uptake was severely reduced and ventilatory efficiency was severely elevated. Multiple pulmonary vascular and right-sided hemodynamic parameters were predictive of functional capacity.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 03 Mar 2023; epub ahead of print</small></div>

<div><h4>Short-term Changes in Hemoglobin and Changes in Functional Status, Quality of Life, and Natriuretic Peptides after initiation of Dapagliflozin in Heart Failure with Reduced Ejection Fraction.</h4><i>Lorenzo M, Miñana G, Palau P, Amiguet M, ... Núñez J, DAPA-VO2 Investigators</i><br /><b>Background</b><br />We aimed to evaluate the effect of dapagliflozin on short-term changes in hemoglobin in patients with stable heart failure with reduced ejection fraction (HFrEF) and whether these changes mediated the effect of dapagliflozin on functional capacity, quality of life, and NT-proBNP.<br /><b>Methods</b><br />It is an exploratory analysis of a randomized, double-blinded clinical trial in which 90 stable patients with HFrEF were randomly allocated to dapagliflozin or placebo to evaluate short-term changes in peak oxygen consumption (peak VO<sub>2</sub>) (NCT04197635). This substudy evaluated 1 and 3-month changes in hemoglobin and whether these changes mediated the effects of dapagliflozin on peak VO2, Minnesota Living-With-Heart-Failure test (MLHFQ), and NT-proBNP.<br /><b>Results</b><br />At baseline, mean hemoglobin was 14.3 ± 1.7 g/dL. Hemoglobin significantly increased in those on dapagliflozin [1-month: +0.45 g/dL (p=0.037), and 3-month:+0.55 g/dL, (p=0.012)]. Changes in hemoglobin positively mediated the changes in peak VO2 at 3-month (59.5%, p<0.001). Changes in hemoglobin significantly mediated the effect of dapagliflozin in MLHFQ at 3-month (-53.2% and -48.7%, p=0.017) and NT-proBNP at 1 and 3-month (-68.0%, p=0.048 and -62.7%, p=0.029, respectively).<br /><b>Conclusions</b><br />In patients with stable HFrEF, dapagliflozin caused a short-term increase in hemoglobin, identifying patients with a greater improvement in maximal functional capacity, QoL, and reduction of NT-proBNP.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 03 Mar 2023; epub ahead of print</small></div>