<div><h4>Cardio-Renal-Metabolic Overlap, Outcomes, and Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction.</h4><i>Ostrominski JW, Thierer J, Claggett BL, Miao ZM, ... Solomon SD, Vaduganathan M</i><br /><b>Background</b><br />Cardio-renal-metabolic (CRM) conditions are individually common among patients with HF, but the prevalence and influence of overlapping CRM conditions in this population have not been well-studied.<br /><b>Objectives</b><br />To evaluate the impact of overlapping CRM conditions on clinical outcomes and treatment effects of dapagliflozin in HF.<br /><b>Methods</b><br />In this post-hoc analysis of DELIVER, we evaluated the prevalence of comorbid CRM conditions (atherosclerotic cardiovascular disease, chronic kidney disease, and type 2 diabetes), their impact on the primary outcome (cardiovascular death or worsening HF), and treatment effects of dapagliflozin by CRM status.<br /><b>Results</b><br />Among 6,263 participants, 1,952 (31%), 2,245 (36%), and 1,236 (20%) had 1, 2, and 3 additional CRM conditions, respectively. HF alone was uncommon (13%). Greater CRM multimorbidity was associated with older age, higher BMI, longer-duration HF, worse health status, and lower LVEF. Risk of the primary outcome increased with higher CRM overlap, with 3 CRM conditions independently associated with highest risk of primary events (adjusted HR, 2.16 [95% CI, 1.72-2.72]; P<0.001) compared with HF alone. Relative benefits of dapagliflozin on the primary outcome were consistent irrespective of the type of CRM overlap (P<sub>interaction</sub>=0.773) and by the number of CRM conditions (P<sub>interaction</sub>=0.734), with greatest absolute benefits among those with highest CRM multimorbidity. Estimated two-year numbers needed to treat with dapagliflozin to prevent one primary event were approximately 52, 39, 33, and 24 for participants with 0, 1, 2, and 3 additional CRM conditions at baseline, respectively. Adverse events between treatment arms were similar across the CRM spectrum.<br /><b>Conclusions</b><br />Cardio-renal-metabolic multimorbidity was common and associated with adverse outcomes among patients with HF and LVEF>40% in DELIVER. Dapagliflozin was safe and effective across the CRM spectrum, with greater absolute benefits among those with highest CRM overlap.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>JACC Heart Fail: 22 May 2023; epub ahead of print</small></div>

<div><h4>Effect of Canagliflozin on Heart Failure Hospitalization in Diabetes According to Baseline Heart Failure Risk.</h4><i>Khan MS, Segar MW, Usman MS, Patel KV, ... Tang WHW, Pandey A</i><br /><b>Background</b><br />In the CANVAS (Canagliflozin Cardiovascular Assessment Study) program, canagliflozin reduced the risk of heart failure (HF) hospitalization among individuals with type 2 diabetes mellitus (T2DM).<br /><b>Objectives</b><br />The purpose of this study was to evaluate heterogeneity in absolute and relative treatment effects of canagliflozin on HF hospitalization according to baseline HF risk as assessed by diabetes-specific HF risk scores (WATCH-DM [Weight (body mass index), Age, hyperTension, Creatinine, HDL-C, Diabetes control (fasting plasma glucose) and QRS Duration, MI and CABG] and TRS-HF<sub>DM</sub> [TIMI Risk Score for HF in Diabetes]).<br /><b>Methods</b><br />Participants in the CANVAS trial were categorized into low, medium, and high risk for HF using the WATCH-DM score (for participants without prevalent HF) and the TRS-HF<sub>DM</sub> score (for all participants). The outcome of interest was time to first HF hospitalization. The treatment effect of canagliflozin vs placebo for HF hospitalization was compared across risk strata.<br /><b>Results</b><br />Among 10,137 participants with available HF data, 1,446 (14.3%) had HF at baseline. Among participants without baseline HF, WATCH-DM risk category did not modify the treatment effect of canagliflozin (vs placebo) on HF hospitalization (P interaction = 0.56). However, the absolute and relative risk reduction with canagliflozin was numerically greater in the high-risk group (cumulative incidence, canagliflozin vs placebo: 8.1% vs 12.7%; HR: 0.62 [95% CI: 0.37-0.93]; P = 0.03; number needed to treat: 22) than in the low- and intermediate-risk groups. When overall study participants were categorized according to the TRS-HF<sub>DM</sub> score, a statistically significant difference in the treatment effect of canagliflozin across risk strata was observed (P interaction = 0.04). Canagliflozin significantly reduced the risk of HF hospitalization by 39% in the high-risk group (HR: 0.61 [95% CI: 0.48-0.78]; P < 0.001; number needed to treat: 20) but not in the intermediate- or low-risk groups.<br /><b>Conclusions</b><br />Among participants with T2DM, the WATCH-DM and TRS-HF<sub>DM</sub> can reliably identify those at high risk for HF hospitalization and most likely to benefit from canagliflozin.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 11 May 2023; epub ahead of print</small></div>

<div><h4>Disentangling Heart Failure and Physical Frailty: Prospective Study of Patients Undergoing Percutaneous Mitral Valve Repair.</h4><i>Metze C, Iliadis C, Körber MI, von Stein J, ... Baldus S, Pfister R</i><br /><b>Background</b><br />Frailty and heart failure share pathophysiology and clinical characteristics.<br /><b>Objectives</b><br />The aim of this study was to analyze the contribution of heart failure to the physical frailty phenotype by examining patients with heart failure before and after percutaneous mitral valve repair (PMVR).<br /><b>Methods</b><br />Frailty according to the Fried criteria (weight loss, weakness, exhaustion, slowness, and low activity) was assessed in consecutive patients before and 6 weeks after PMVR.<br /><b>Results</b><br />118 of 258 patients (45.7%) (mean age: 78 ± 9 years, 42% female, 55% with secondary mitral regurgitation) were frail at baseline, which significantly decreased to 74 patients (28.7 %) at follow-up (P < 0.001). The frequency of frailty domains slowness, exhaustion, and inactivity significantly decreased, whereas weakness remained unchanged. Baseline frailty was significantly associated with comorbidities, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and functional capacity, whereas frailty after PMVR was not associated with NT-proBNP levels. Predictors of postprocedural reversibility of frailty were NYHA functional class <IV, absence of weakness, and lower frailty score. In comparison with patients who were persistently nonfrail (reference group HR: 1), the risk of mortality continuously increased for patients who experienced new frailty (HR: 1.41 [95% CI: 0.41-4.86]), those who had reversal of frailty (HR: 2.17 [95% CI: 1.03-4.57]), and those who were persistently frail (HR: 3.26 [95%: CI 1.62-6.57]; P = 0.006 for trend).<br /><b>Conclusions</b><br />Treatment of mitral regurgitation in patients with heart failure is associated with almost a halved burden of physical frailty, particularly in patients with a less advanced phenotype. Considering the prognostic relevance of frailty dynamics, this data warrants further evaluation of the concept of frailty as a primary treatment target.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 11 May 2023; epub ahead of print</small></div>

<div><h4>Utilization Rates of SGLT2 Inhibitors Among Patients With Type 2 Diabetes, Heart Failure, and Atherosclerotic Cardiovascular Disease: Insights From the Department of Veterans Affairs.</h4><i>Hussain A, Ramsey D, Lee M, Mahtta D, ... Navaneethan SD, Virani SS</i><br /><b>Background</b><br />Multiple clinical trials have demonstrated significant cardiovascular benefit with use of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with type 2 diabetes (T2DM) and heart failure (HF) irrespective of ejection fraction. There are limited data evaluating real-world prescription and practice patterns of SGLT2 inhibitors.<br /><b>Objectives</b><br />The authors sought to assess utilization rates and facility-level variation in the use among patients with established atherosclerotic cardiovascular disease (ASCVD), HF, and T2DM using data from the nationwide Veterans Affairs health care system.<br /><b>Methods</b><br />The authors included patients with established ASCVD, HF, and T2DM seen by a primary care provider between January 1, 2020, and December 31, 2020. They assessed the use of SGLT2 inhibitors and the facility-level variation in their use. Facility-level variation was computed using median rate ratios, a measure of likelihood that 2 random facilities differ in use of SGLT2 inhibitors.<br /><b>Results</b><br />Among 105,799 patients with ASCVD, HF, and T2DM across 130 Veterans Affairs facilities, 14.6% received SGLT2 inhibitors. Patients receiving SGLT2 inhibitors were younger men with higher hemoglobin A1c and estimated glomerular filtration rate and were more likely to have HF with reduced ejection fraction and ischemic heart disease. There was significant facility-level variation of SGLT2 inhibitor use, with an adjusted median rate ratio of 1.55 (95% CI: 1.46-1.64), indicating a 55% residual difference in SGLT2 inhibitor use among similar patients with ASCVD, HF, and T2DM receiving care at 2 random facilities.<br /><b>Conclusions</b><br />Utilization rates of SGLT2 inhibitors are low in patients with ASCVD, HF, and T2DM, with high residual facility-level variation. These findings suggest opportunities to optimize SGLT2 inhibitor use to prevent future adverse cardiovascular events.<br /><br />Published by Elsevier Inc.<br /><br /><small>JACC Heart Fail: 11 May 2023; epub ahead of print</small></div>

<div><h4>Long-Term Exposure to Road Traffic Noise and Incident Heart Failure: Evidence From UK Biobank.</h4><i>Yang T, Hu X, Wang J, Rao S, ... Huang J, Rahimi K</i><br /><b>Background</b><br />Evidence on road traffic noise and heart failure (HF) is limited, and little is known on the potential mediation roles of acute myocardial infarction (AMI), hypertension, or diabetes.<br /><b>Objectives</b><br />The purpose of this study was to evaluate the impacts of long-term road traffic noise exposure on the risk of incident HF considering air pollution, and explore the mediations of the previously mentioned diseases.<br /><b>Methods</b><br />This prospective study included 424,767 participants without HF at baseline in UK Biobank. The residential-level noise and air pollution exposure was estimated, and the incident HF was identified through linkages with medical records. Cox proportional hazard models were used to estimate HRs. Furthermore, time-dependent mediation was performed.<br /><b>Results</b><br />During a median 12.5 years of follow-up, 12,817 incident HF were ascertained. The HRs were 1.08 (95% CI: 1.00-1.16) per 10 dB[A] increase in weighted average 24-hour road traffic noise level (L<sub>den</sub>), and 1.15 (95% CI: 1.02-1.31) for exposure to L<sub>den</sub> >65dB[A] compared with the reference category (L<sub>den</sub> ≤55dB[A]), respectively. Furthermore, the strongest combined effects were found in those with both high exposures to road traffic noise and air pollution including fine particles and nitrogen dioxide. Prior AMI before HF within 2 years\' time interval mediated 12.5% of the association of road traffic noise with HF.<br /><b>Conclusions</b><br />More attention should be paid and a preventive strategy should be considered to alleviate the disease burden of HF related to road traffic noise exposure, especially in participants who survived AMI and developed HF within 2 years.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 10 May 2023; epub ahead of print</small></div>

<div><h4>Pre-Heart Failure Longitudinal Change in a Hispanic/Latino Population-Based Study: Insights From the Echocardiographic Study of Latinos.</h4><i>Kuno T, Vasquez N, April-Sanders AK, Swett K, ... Kitzman D, Rodriguez CJ</i><br /><b>Background</b><br />Pre-heart failure (pre-HF) is an entity known to progress to symptomatic heart failure (HF).<br /><b>Objectives</b><br />This study aimed to characterize pre-HF prevalence and incidence among Hispanics/Latinos.<br /><b>Methods</b><br />The Echo-SOL (Echocardiographic Study of Latinos) assessed cardiac parameters on 1,643 Hispanics/Latinos at baseline and 4.3 years later. Prevalent pre-HF was defined as the presence of any abnormal cardiac parameter (left ventricular [LV] ejection fraction <50%; absolute global longitudinal strain <15%; grade 1 or more diastolic dysfunction; LV mass index >115 g/m<sup>2</sup> for men, >95 g/m<sup>2</sup> for women; or relative wall thickness >0.42). Incident pre-HF was defined among those without pre-HF at baseline. Sampling weights and survey statistics were used.<br /><b>Results</b><br />Among this study population (mean age: 56.4 years; 56% female), HF risk factors, including prevalence of hypertension and diabetes, worsened during follow-up. Significant worsening of all cardiac parameters (except LV ejection fraction) was evidenced from baseline to follow-up (all P < 0.01). Overall, the prevalence of pre-HF was 66.7% at baseline and the incidence of pre-HF during follow-up was 66.3%. Prevalent and incident pre-HF were seen more with increasing baseline HF risk factor burden as well as with older age. In addition, increasing the number of HF risk factors increased the risk of prevalence of pre-HF and incidence of pre-HF (adjusted OR: 1.36 [95% CI: 1.16-1.58], and adjusted OR: 1.29 [95% CI: 1.00-1.68], respectively). Prevalent pre-HF was associated with incident clinical HF (HR: 10.9 [95% CI: 2.1-56.3]).<br /><b>Conclusions</b><br />Hispanics/Latinos exhibited significant worsening of pre-HF characteristics over time. Prevalence and incidence of pre-HF are high and are associated with increasing HF risk factor burden and with incidence of cardiac events.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 04 May 2023; epub ahead of print</small></div>