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Background: Efficacy and tolerability of sacubitril/valsartan (Sac/Val) is not well characterized in heart failure (HF) with ejection fraction >40% initiated in-hospital. Thus, this prespecified PARAGLIDE-HF (Prospective Comparison of ARNI With ARB Given Following Stabilization In Decompensated HFpEF) analysis assessed the effects of Sac/Val versus valsartan (Val) by location of initiation in HF with ejection fraction >40% and recent worsening HF., Methods and Results: This analysis of the double-blind, randomized controlled trial assessed patients by in-hospital and out-of-hospital (≤30 days of worsening HF) initiation. The primary end point was time-averaged proportional change in NT-proBNP (N-terminal pro-B-type natriuretic peptide) from baseline through weeks 4 and 8. A secondary hierarchical outcome consisted of cardiovascular death, HF hospitalizations, urgent HF visits, and NT-proBNP change. Safety end points were symptomatic hypotension, hyperkalemia, and worsening renal function. Overall, 324 (70%, 162 Sac/Val, 162 Val) were initiated in-hospital and 142 (71 Sac/Val, 71 Val) out-of-hospital. There was no evidence of a statistically significant differential treatment benefit of Sac/Val versus Val on NT-proBNP change by location of initiation (in-hospital, 0.86 [95% CI, 0.70-1.05] and out-of-hospital, 0.87 [95% CI, 0.70-1.09]; P interaction =0.99). The win ratio for the hierarchical outcome was 1.09 (95% CI, 0.82-1.45; P =0.57) for in-hospital and 1.43 (95% CI, 0.91-2.26; P =0.12) for out-of-hospital. For the safety end points of symptomatic hypotension, hyperkalemia, and worsening renal function, no statistically significant differences in tolerability were seen between in-hospital and out-hospital initiation ( P interaction >0.1)., Conclusions: Sac/Val provided consistent benefit compared with Val, whether initiated in-hospital or out-of-hospital in HF with ejection fraction >40% with a recent worsening HF event, demonstrating an opportunity to improve postdischarge outcomes by initiating Sac/Val during hospitalization.

Background: Cardiovascular disease is a common comorbidity in chronic obstructive pulmonary disease (COPD). Yet cardiovascular disease and risk is under diagnosed in COPD and is often undertreated, increasing the risk of cardiopulmonary events., Methods: We formed a Global Working Group of experts in COPD and cardiovascular disease to produce a consensus statement detailing the identification and management of cardiopulmonary risk in patients with COPD. We conducted virtual meetings supplemented by remote working and communication. The Chairs (CPG, MB) proposed a draft consensus statement, which was further developed by the Global Working Group. The selection of the final consensus statement and key points were obtained using the modified Delphi method., Results: The consensus statement is, 'Given the high burden of fatal and non-fatal major cardiovascular and respiratory events in patients with COPD it is important that cardiopulmonary risk is assessed and managed'. Patients with cardiovascular risk factors or disease who have regular cough or expectoration, recurrent "chest infections", a significant smoking history, or dyspnoea should complete spirometry to confirm the presence of COPD. Prevalent and incident cardiovascular disease and risk in patients with COPD, including heart failure, dyslipidaemia, hypertension, ischaemic heart disease and atrial fibrillation, should be managed according to clinical guidelines. In addition, COPD exacerbation risk in patients with COPD should be addressed to reduce cardiopulmonary risk. Enhanced integration with specialists in cardiology, pulmonology and primary care is recommended., Conclusions: The identification and management of cardiopulmonary risk in patients with COPD is an unmet public health need that can be addressed through shared understanding and multidisciplinary working to improve cardiopulmonary outcomes., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Importance: Worsening heart failure (HF) is commonly managed in the outpatient setting with adjustments in oral diuretic therapy. The effect of the nonsteroidal mineralocorticoid receptor antagonist finerenone on outpatient worsening HF events in patients with mildly reduced or preserved ejection fraction is unknown., Objective: To evaluate the effect of finerenone on outpatient worsening HF events requiring oral diuretic intensification among patients with HF with mildly reduced or preserved ejection fraction., Design, Setting, and Participants: This is a secondary analysis of the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF), a global, multicenter randomized clinical trial. Patients had HF and an ejection fraction of 40% or greater. Data analysis was conducted from September 1 to December 10, 2024., Intervention: Participants were randomized 1:1 to finerenone or placebo., Main Outcomes and Measures: Primary outcome events (cardiovascular death, HF hospitalization, and outpatient urgent HF visit requiring intravenous diuretic therapy) were centrally adjudicated. In this prespecified analysis, outpatient oral diuretic intensification events were defined as initiations of loop or thiazide diuretic or increases in loop diuretic dosage. The risk of all-cause death following each type of worsening HF event (HF hospitalization, urgent HF visit, or outpatient oral diuretic intensification) and the effect of finerenone on outpatient oral diuretic intensification alone or as part of an extended composite outcome with primary outcome events were evaluated., Results: A total of 6001 participants (mean [SD] age, 72.0 [9.6] years; 2732 [46%] female) were enrolled. First worsening HF events included 664 HF hospitalizations, 87 urgent HF visits, and 1250 oral diuretic intensifications. Rates of death were higher following worsening HF: 27.7 (95% CI, 24.3-31.5) per 100 patient-years after HF hospitalization, 13.6 (95% CI, 8.8-21.1) per 100 patient-years after urgent HF visit, and 11.6 (95% CI, 10.2-13.1) per 100 patient-years after outpatient oral diuretic intensification compared with 4.5 (95% CI, 4.2-4.9) per 100 patient-years for patients without worsening HF. Adding outpatient oral diuretic intensification to the primary outcome increased the number of patients experiencing events from 1343 to 2238. Finerenone reduced outpatient oral diuretic intensification alone (hazard ratio [HR], 0.89 [95% CI, 0.80-0.98]; P = .02) and in an extended composite outcome that further included cardiovascular death, HF hospitalization, and urgent HF visit (HR, 0.85 [95% CI, 0.78-0.92]; P < .001)., Conclusions and Relevance: Outpatient worsening HF events requiring oral diuretic intensification were common, associated with poor prognosis, and reduced by finerenone in patients with HF with mildly reduced or preserved ejection fraction., Trial Registration: ClinicalTrials.gov Identifier: NCT04435626.

Background: The win ratio (WR) is an emerging alternative for reporting composite outcomes, prioritizing clinically significant events such as mortality while incorporating surrogate measures. However, its benefits should be weighed against limitations, particularly the influence of lower hierarchical outcomes. This secondary analysis of the PARAGLIDE-HF trial performed a WR sensitivity analysis using a modified hierarchical composite outcome to assess the utility of WR sensitivity analysis and the efficacy of sacubitril/valsartan versus valsartan., Methods: PARAGLIDE-HF compared sacubitril/valsartan with valsartan in heart failure (HF) patients with ejection fraction >40% (N = 466). A hierarchical outcome in the primary analysis included cardiovascular death, HF hospitalizations, urgent HF visits, and change in N-terminal pro-B-type natriuretic peptide (NT-proBNP), with a 25% decrease considered a win. In the prespecified subgroup with ejection fraction ≤60% (N = 357), sacubitril/valsartan showed a treatment effect on the hierarchical outcome (WR, 1.46; 95% CI, 1.08-1.97). Sensitivity analyses for this subgroup included: (1) excluding NT-proBNP change, (2) substituting the 25% proportion change of NT-proBNP with 10% or 50%, and (3) including renal outcomes within the hierarchical outcome. In addition to the WR, the win odds (WO), in which 50% of the ties are allocated to both the numerator and denominator of the WR-a potentially more suitable modification of the WR that accounts for the presence of ties-were presented., Results: Excluding NT-proBNP (WR, 1.49; 95% CI, 1.00-2.22; WO, 1.12; 95% CI, 1.00-1.26), adjusting the NT-proBNP threshold from 25% to 10% or 50% (WR, 1.41; 95% CI, 1.06-1.89; WO, 1.27; 95% CI, 1.04-1.56 for 10%; and WR, 1.54; 95% CI, 1.11-2.12; WO, 1.25; 95% CI, 1.06-1.48 for 50%), and incorporating renal outcomes (WR, 1.44; 95% CI, 1.07-1.94; WO, 1.28; 95% CI, 1.05-1.56) consistently favored sacubitril/valsartan., Conclusions: Multiple WR sensitivity analyses support a consistent treatment benefit of sacubitril/valsartan versus valsartan in patients with ejection fraction >40% to 60%. Future studies could consider prespecifying WR sensitivity analysis for comprehensive assessment of treatment effects., Trial Registration: PARAGLIDE-HF; ClinicalTrials.gov ID, NCT03988634 (https://clinicaltrials.gov/study/NCT03988634)., Competing Interests: Conflict of interest Dr Hernandez has received research grants from American Regent, Amgen, AstraZeneca, Bayer, Bayer, Boehringer Ingelheim, Cytokinetics, Merck, Novartis, Somologic, and Verily; and has served as a consultant for Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Merck, Novartis, and Novo Nordisk. Dr Velazquez has received grants from Novartis and the National Heart, Lung, and Blood Institute/National Institutes of HealthNHLBI and serves on advisory committees for REDVIA, ABIOMED and CardioMech. Drs Ward, Williamson, and Sarwat are employees of Novartis. Dr Starling serves on the steering committee for the PARAGLIDE trial sponsored by Novartis. Dr Desai has received research grants (to BWH) from Abbott, Alnylam, AstraZeneca, Bayer, and Novartis; and has received personal consulting fees from Abbott, Alnylam, AstraZeneca, Avidity Bio- pharma, Axon Therapeutics, Bayer, Biofourmis, Cytokinetics, Glax- oSmithKline, Medpace, Merck, New Amsterdam, Novartis, Parexel, Regeneron, River2Renal, Roche, Verily, and Veristat. Dr Zieroth received research grant support, served on advisory boards for, or speaker engagements with Abbott, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Eli Lilly, GSK, Medtronic, Merck, Novartis, Novo-Nordisk, Pfizer and Vifor Pharma; and serves on a clinical trial committee or as a national lead for studies sponsored by AstraZeneca, Boehringer Ingelheim, Merck, Novartis, Pfizer, Salubris Bio. Nonindustry: Canadian Medical and Surgical KT Group, CCS, CHFS, Charite, EOCI, Liv, Medscape, Ology, PACE-CME, Radcliffe, Reach MD, Translational Medicine Academy. Dr Solomon has received research grants from Alnylam, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Cytokinetics, Eidos, GlaxoSmithKline, Ionis, Lilly, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, Actelion, Amgen, Bellerophon, Celladon, Gilead, Mesoblast, Neurotronik, and lure 11 and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. Dr Mentz has received research support and/or honoraria from Novartis, Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Medable, Merck, Novo Nordisk, Pharmacosmos, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Treatment with finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), improved outcomes in patients with heart failure with mildly reduced or preserved ejection fraction in FINEARTS-HF, but was associated with increased levels of serum potassium in follow-up., Objective: To investigate the frequency and predictors of serum potassium level greater than 5.5 mmol/L and less than 3.5 mmol/L and examine the treatment effect associated with finerenone, relative to placebo, on clinical outcomes based on postrandomization potassium levels., Design, Setting, and Participants: Secondary analysis of the FINEARTS-HF multicenter, randomized clinical trial, performed between September 14, 2020, and January 10, 2023, with a median follow-up of 32 months (final date of follow-up: June 14, 2024). Patients with heart failure and left ventricular ejection fraction greater than or equal to 40%, New York Heart Association class II to IV symptoms, and elevated natriuretic peptides were included., Intervention: Participants received finerenone or placebo., Main Outcomes and Measures: The primary outcome was a composite of total worsening heart failure events or cardiovascular death., Results: A total of 6001 participants were included (3003 randomized to receive finerenone and 2998 randomized to receive placebo). The increase in serum potassium was greater in the finerenone group than the placebo group at 1 month (median [IQR] difference, 0.19 [0.17-0.21] mmol/L) and 3 months (median [IQR] difference, 0.23 [0.21-0.25] mmol/L), which persisted for the remainder of trial follow-up. Finerenone increased the risks of potassium level increasing to greater than 5.5 mmol/L (hazard ratio [HR], 2.16 [95% CI, 1.83-2.56]; P < .001) and decreased the risks for potassium level decreasing to less than 3.5 mmol/L (HR, 0.46 [95% CI, 0.38-0.56]; P < .001). Both low (< 3.5 mmol/L; HR, 2.49 [95% CI, 1.8-3.43]) and high (>5.5 mmol/L; HR, 1.64 [95% CI, 1.04-2.58]) potassium levels were associated with higher subsequent risks of the primary outcome in both treatment groups. Nevertheless, the risk of the primary outcome was generally lower in patients treated with finerenone compared with placebo, even in those whose potassium level increased to greater than 5.5 mmol/L., Conclusions and Relevance: In patients with heart failure with mildly reduced or preserved ejection fraction, finerenone resulted in more frequent hyperkalemia and less frequent hypokalemia. However, with protocol-directed surveillance and dose adjustment, clinical benefit associated with finerenone relative to placebo was maintained even in those whose potassium level increased to greater than 5.5 mmol/L., Trial Registration: ClinicalTrials.gov Identifier: NCT04435626.

Aims: In the EMPACT-MI trial, empagliflozin reduced heart failure (HF) hospitalizations but not mortality in acute myocardial infarction (MI). Contemporary reports of clinical event rates with and without type 2 diabetes mellitus (T2DM) in acute MI trials are sparse. The treatment effect of empagliflozin in those with and without T2DM in acute MI is unknown., Methods and Results: A total of 6522 patients with acute MI with newly reduced left ventricular ejection fraction (LVEF) to <45%, congestion, or both, were randomized to empagliflozin 10 mg or placebo. The primary endpoint was time to first HF hospitalization or all-cause death. Rates of endpoints with and without T2DM and the efficacy and safety of empagliflozin according to T2DM status were assessed. Overall, 32% had T2DM; 14% had pre-diabetes; 16% were normoglycaemic; 38% had unknown glycaemic status. Patients with T2DM, compared to those without T2DM, were at higher risk of time to first HF hospitalization or all-cause death (hazard ratio [HR] 1.44; 95% confidence interval [CI] 1.06-1.95) and all-cause death (HR 1.70; 95% CI 1.13-2.56). T2DM did not confer a higher risk of first HF hospitalization (HR 1.22, 95% CI 0.82-1.83). Empagliflozin reduced first and total HF hospitalizations, but not all-cause mortality, regardless of presence or absence of T2DM. The safety profile of empagliflozin was the same with and without T2DM., Conclusion: Patients with acute MI, LVEF <45% and/or congestion who had T2DM were at a higher risk of mortality than those without T2DM. Empagliflozin reduced first and total HF hospitalizations regardless of the presence or absence of T2DM., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background and Aims: There is a gap in knowledge about implementing diagnostic tools and therapy for heart failure with preserved ejection fraction (HFpEF) in clinical practice. This survey aimed to assess real-world practice in HFpEF diagnosis and treatment in the international medical community., Methods: An independent academic web-based 29-question survey was designed by a group of heart failure specialists and posted by email and through scientific societies and social networks to a broad community of physicians worldwide., Results: 1.460 physicians from 95 countries answered the survey, with a mean age of 42.2±10.4 years, 39.4 % females, and 85.1 % were cardiologists. The left ventricular ejection fraction cut-off value selected for HFpEF diagnosis was 50 % for 89 % of participants. The scores for the probability of diagnosis of HFpEF were used only by 47.2 %, and H2FPEF was the most used score (31 %). Natriuretic peptides were used by 87.4 % of participants for the diagnostic workup, while the diastolic stress test was only used by 26.2 %. 54.4 % of participants chose SGLT2 inhibitors as their first drug treatment, followed by diuretics (18.6 %) and ACE inhibitors (8.4 %)., Conclusions: In an international academic survey on HFpEF management, the criteria for screening and diagnosis of HFpEF patients remain aligned with classic international guidelines with a low use of diagnostic scores. SGLT2i is the leading therapeutic drug class used for this heterogeneous patient population. These results raise the need to improve education and awareness on diagnosing and managing HFpEF patients., Competing Interests: Declaration of competing interest CS has received honoraria as speaker for Speaker for Novartis, Servier, Merck, Sanofi Pfizer, Astrazeneca, Boehringer Ingelheim, Novo Nordisk, Ely Lilly and as advisor for Bayer, Merck and Novo Nordisk, CF has received travel fees from Pfizer, NM has received consulting fees from Bayer and Amgen and as speaker for Astrazeneca, Novartis and Boehringer Ingelheim, support for attending meetings from Astrazeneca and Novartis, FR has not received personal payments by pharmaceutical companies or device manufacturers in the last 3 years (remuneration for the time spent in activities, such as participation as steering committee member of clinical trials and member of the Pfizer Research Award selection committee in Switzerland, were made directly to the University of Zurich). The Department of Cardiology (University Hospital of Zurich/University of Zurich) reports research-, educational- and/or travel grants from Abbott, Abiomed, Alnylam,Amarin, Amgen, Astra Zeneca, At the Limits Ltd., Bayer, Biotronik, BMS, Boehringer Ingelheim, Boston Scientific, Bracco, CM Microport, Concept Medical, CTI, Daiichi Sankyo, Edwards Lifesciences, FomF GmbH, Hamilton Health Sciences, IHF, Innosuisse, IumiraDX, Kantar, LabPoint, MedAlliance, Medcon International, Medical Education Global Solutions, Medtronic, MicroPort, Monocle, Novartis, Novo Nordisk, OM Pharma, Pfizer, Quintiles Switzerland Sarl, RecorMedical, Roche Diagnostics, Roche Pharma, Sahajanand IN, Sanofi, Sarstedt AG, Servier, Terumo Deutschland, Trama Solutions, V- Wave, Vifor, ZOLL. These grants do not impact on Prof. Ruschitzka`s personal remuneration. IJI received support for travel to meetings from Novartis. DM received payment as a speaker for Novartis, Pfizer, Astra Zeneca and support for attending meetings from Pfizer, Astrazeneca and abbot. GR reports grants and personal fees from Astra Zeneca, personal fees and other from Boheringer Ingelheim, other from Bayer, personal fees from Anlylam, other from Medtronic, grants from Servier, grants and non-financial support from Menarini, personal fees from Viatris, grants from Vifor Pharma, outside the submitted work. GGR reports personal fees from Pfizer, personal fees from CSL Vifor, personal fees from Astra Zeneca, personal fees from PTC therapeutics, personal fees from Bristol MS, personal fees from Boehringer Ingelheim, personal fees from Servier, outside the submitted work; GE reports personal fees from NOVO NORDISK, during the conduct of the study; IM reports grants from Boehringer Ingelheim, during the conduct of the study, SZ Served on advisory boards for, or speaker engagements with Abbott, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Eli Lilly, GSK, Medtronic, Merck, Novartis, Novo-Nordisk, Pfizer and Vifor Pharma; and serves on a clinical trial committee or as a national lead for studies sponsored by AstraZeneca, Boehringer Ingelheim, Merck, Novartis, Pfizer, Salubris Bio and Served on advisory boards for, or speaker engagements with Abbott, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Eli Lilly, GSK, Medtronic, Merck, Novartis, Novo-Nordisk, Pfizer and Vifor Pharma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In PARAGLIDE-HF, in patients with ejection fraction (EF) > 40%, stabilized after worsening heart failure (WHF), sacubitril/valsartan led to greater reduction in plasma NT-proBNP levels and was associated with clinical benefit compared to valsartan alone, despite more symptomatic hypotension (SH). Concern about SH may be limiting the use of sacubitril/valsartan in appropriate patients., Methods: We characterized patients by the occurrence of SH (investigator-reported) after randomization to either sacubitril/valsartan or valsartan. A key trial inclusion criterion was systolic blood pressure (SBP) ≥ 100 mmHg for the preceding 6 hours and no SH. We also compared outcomes based on baseline SBP stratified by the median blood pressure. The primary endpoint was time-averaged proportional change in NT-proBNP levels from baseline through weeks 4 and 8. A secondary hierarchical outcome (win ratio) consisted of: (1) cardiovascular death; (2) hospitalizations due to HF; (3) urgent HF visits; and (4) change in NT-proBNP levels., Results: Among 466 randomized patients, 92 (19.7%) experienced SH (sacubitril/valsartan, n = 56 [24.0%]; valsartan, n = 36 [15.5%]; P = 0.020). The median time to the first SH event was similar between treatment arms (18 days vs 15 days, respectively; P = 0.42) as was the proportion of first SH events classified as serious by investigators. Patients who experienced SH with sacubitril/valsartan were more likely to be white (OR 1.87 [95% CI: 0.31, 11.15]), to have a lower baseline SBP (per 10 mmHg increase, OR 0.68 [95% CI: 0.55, 0.85]), or to have a left ventricular ejection fraction (LVEF) of > 60% (OR 2.21 [95% CI: 1.05, 4.65]). Time-averaged change in NT-proBNP levels did not differ between patients with baseline SBP ≥ 128 mmHg vs SBP < 128 mmHg (interaction, P = 0.43). The composite hierarchical outcome for sacubitril/valsartan in patients with baseline SBP ≥ 128 mmHg had a win ratio of 1.34 ([95% CI: 0.91, 1.99]; P = 0.096) vs SBP < 128 mmHg with a win ratio of 1.09 ([95%CI: 0.73, 1.66]; P = 0 .62; interaction P value = 0.42)., Conclusion: Among patients with LVEF > 40% stabilized after WHF, incident SH was more common with sacubitril/valsartan compared with valsartan. SH was associated with lower baseline SBP, being white, and having higher LVEF. Treatment benefits with sacubitril/valsartan may be more pronounced in patients with higher baseline SBP and lower LVEF (≤ 60%). (Funded by Novartis Pharmaceutical Corporation; ClinicalTrials.gov number, NCT03988634.)., Competing Interests: Disclosures MF was supported by the NIH and Doris Duke, received consulting fees from Abbott, Ajax, Alio Health, Alleviant, Artha, Audicor, AxonTherapies, Bayer, Bodyguide, Bodyport, Boston Scientific, Broadview, Cadence, Cardioflow, Cardionomics, Coridea, CVRx, Daxor, Deerfield Catalyst, Edwards LifeSciences, Echosens, EKO, Feldschuh Foundation, Fire1, FutureCardia, Galvani, Gradient, Hatteras, HemodynamiQ, Impulse Dynamics, Intershunt, Medtronic, Merck, NIMedical, NovoNordisk, NucleusRx, NXT Biomedical, Orchestra, Pharmacosmos, PreHealth, Presidio, Procyreon, ReCor, Rockley, SCPharma, Shifamed, Splendo, Summacor, SyMap, Verily, Vironix, Viscardia, and Zoll. DAM is a member of the TIMI Study Group, which has received institutional research grant support through Brigham and Women's Hospital from Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc., AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc., Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc., Janssen Research and Development, LLC, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Roche, Siemens Healthcare Diagnostics, Softcell Medical Limited, and Zora Biosciences and has received consulting fees from Abbott Laboratories, ARCA Biopharma, Inflammatix, Merck, Novartis, and Roche Diagnostics. KS serves as an advisory board member and/or consultant to AstraZeneca, Alleviant, Bayer, Boehringer-Ingelheim, Imbria, Novartis, NovoNordisk, RIVUS, and ViCardia. She receives grant funding from Amgen and American Heart Association. SDS has received research grants from Alnylam, AstraZeneca, Bellerophon, Bayer, BMS, Cytokinetics, Eidos, GSK, Ionis, Lilly, MyoKardia, NIH/NHLBI, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, and Theracos, and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boeringer-Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, and Akros. RCS serves on the steering committee for the PARAGLIDE trial, sponsored by Novartis. EJV reports grants from Novartis, Amgen, Phillips, and NHLBI/NIH. SDS has received research grants has received research grants from Alnylam, AstraZeneca, Bellerophon, Bayer, BMS, Cytokinetics, Eidos, Gossamer, GSK, Ionis, Lilly, MyoKardia, NIH/NHLBI, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, US2.AI and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boeringer-Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, Valo. ASD has received research grants (to BWH) from Abbott, Alnylam, AstraZeneca, Bayer, Novartis and personal consulting fees from Abbott, Alnylam, AstraZeneca, Avidity Biopharma, Axon Therapeutics, Bayer, Biofourmis, Cytokinetics, GlaxoSmithKline, Medpace, Merck, New Amsterdam, Novartis, Parexel, Regeneron, River2Renal, Roche, Verily, Veristat. SZ received research grant support, served on advisory boards for or speaker engagements with Abbott, Akcea AstraZeneca, Amgen, Alnylam, Bayer, BMS, Boehringer Ingelheim, Eli Lilly, GSK, Janssen, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Servier and Vifor Pharma; and serves on a clinical trial committee or as a national lead for studies sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, and Pfizer. EB reports grant support to his institution from Novartis for the conduct of the PIONEER-HF trial (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP [N-terminal pro-B type natriuretic peptide] in Patients Stabilized From an Acute HF Episode), for serving on the executive committee of the PARADISE-MI (Prospective ARNI [angiotensin receptor neprilysin inhibitor] vs ACE [angiotensin-converting enzyme] Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After Myocardial Infarction) trial and the Steering Committee of the PARAGLIDE-HF trial, and for participation in an advisory board meeting. RJM receives research support and/or honoraria from Novartis, Abbott, AmericanRegent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Medable, Merck, Novo Nordisk, Pharmacosmos, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. JHW, SS and KMW are employees of Novartis. AFH reports research grants from American Regent, Amgen, AstraZeneca, Bayer, Bayer, Boehringer Ingelheim, Cytokinetics, Merck, Novartis, Somologic, Verily and consulting from Amgen, AstraZeneca, Bayer, Bristol-Myers Squib Boehringer Ingelheim, Boston Scientific, Cytokinetics, Merck, Novartis, and Novo Nordisk. All other authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Clinical practice guidelines are commonly written by professional societies in high-income countries (HIC) with limited anticipation of implementation obstacles in other environments. We used heart failure (HF) guidelines as a paradigm to examine this concern, by conducting a survey to understand clinicians' ability to implement HF guidelines and their perceptions of the current HF guideline applicability in low- and middle-income countries (LMIC)., Methods and Results: An online survey of physicians in the database of the Translational Medicine Academy who treat HF patients was offered by email from 5 October to 27 November 2023, inquiring of participants' demographic information, experience, and views of HF guidelines as related to their practice. Of 2622 participating clinicians, 1592 partially completed, and an additional 1030 fully completed the survey. Participants were from 138 countries; 668 practiced in HIC, and 1954 in LMIC. Those from LMIC regarded HF guidelines to be less applicable in their country than did those from HIC (p = 0.0002). Of all those responding, 75.3% indicated that it was somewhat or mostly true that the HF guidelines were mostly applicable to HIC. Those from LMIC, but not HIC indicated that the greatest implementation obstacle was that the guidelines were for HIC (51.3% vs. 43.1%; p = 0.0387). A significantly higher proportion of respondents from LMIC indicated that resources for caring for their patients were somewhat or mostly limiting in most cases, than did those in HIC (41.6% vs. 32.5%, p = 0.0068)., Conclusion: This survey examined the widely-held thought that HF guidelines are broadly applicable to all regions of the world, concluding that such a perception is incorrect. Clinicians from LMIC view the absence of consideration of local resource limitations as the greatest obstacle for guideline implementation. The results regarding HF guidelines likely also have implications for other guidelines and resultant patient outcomes., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Steroidal mineralocorticoid receptor antagonists reduce morbidity and mortality among patients with heart failure and reduced ejection fraction, but their efficacy in those with heart failure and mildly reduced or preserved ejection fraction has not been established. Data regarding the efficacy and safety of the nonsteroidal mineralocorticoid receptor antagonist finerenone in patients with heart failure and mildly reduced or preserved ejection fraction are needed., Methods: In this international, double-blind trial, we randomly assigned patients with heart failure and a left ventricular ejection fraction of 40% or greater, in a 1:1 ratio, to receive finerenone (at a maximum dose of 20 mg or 40 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of total worsening heart failure events (with an event defined as a first or recurrent unplanned hospitalization or urgent visit for heart failure) and death from cardiovascular causes. The components of the primary outcome and safety were also assessed., Results: Over a median follow-up of 32 months, 1083 primary-outcome events occurred in 624 of 3003 patients in the finerenone group, and 1283 primary-outcome events occurred in 719 of 2998 patients in the placebo group (rate ratio, 0.84; 95% confidence interval [CI], 0.74 to 0.95; P = 0.007). The total number of worsening heart failure events was 842 in the finerenone group and 1024 in the placebo group (rate ratio, 0.82; 95% CI, 0.71 to 0.94; P = 0.006). The percentage of patients who died from cardiovascular causes was 8.1% and 8.7%, respectively (hazard ratio, 0.93; 95% CI, 0.78 to 1.11). Finerenone was associated with an increased risk of hyperkalemia and a reduced risk of hypokalemia., Conclusions: In patients with heart failure and mildly reduced or preserved ejection fraction, finerenone resulted in a significantly lower rate of a composite of total worsening heart failure events and death from cardiovascular causes than placebo. (Funded by Bayer; FINEARTS-HF ClinicalTrials.gov number, NCT04435626.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: In Canada, COPD represents a significant burden to the patient and health system, as it is often under or misdiagnosed and sub-optimally treated. Cardiovascular disease (CVD) is a common co-morbidity in COPD and there is significant interplay between these two chronic conditions. Across all stages of COPD disease severity, deaths can be attributed not only to respiratory causes but also to cardiovascular-related factors. The established links between COPD and CVD suggest the need for a greater degree of collaboration between respirologists and cardiologists. This modified Delphi consensus was initiated to consider how optimal COPD care can be delivered within Canada, with specific consideration of reducing cardiopulmonary risk and outcomes in COPD patients., Methods: A steering group with interest in the management of COPD and CVD from primary care, cardiology, and respirology identified 40 statements formed from four key themes. A 4-point Likert scale questionnaire was sent to healthcare professionals working in COPD across Canada by an independent third party to assess agreement (consensus) with these statements. Consensus was defined as high if ≥75% and very high if ≥90% of respondents agreed with a statement., Results: A total of 100 responses were received from respirologists (n=30), cardiologists (n=30), and primary care physicians (n=40). Consensus was very strong (≥90%) in 28 (70%) statements, strong (≥75 and <90%) in 7 (17.5%) statements and was not achieved (<75%) in 5 (12.5%) of statements., Conclusion: Based on the consensus scores, 9 key recommendations were proposed by the steering group. These focus on the need to comprehensively risk stratify and manage COPD patients to help prevent exacerbations. Consensus within this study provides a call to action for the expeditious implementation of the latest COPD guidelines from the Canadian Thoracic Society., Competing Interests: No authors received honoraria from AstraZeneca for this project. Previous honoraria received by the authors includes: M Bhutani reports grants, contracts, consulting fees, support for travel, or honoraria from CIHR, AstraZeneca, GlaxoSmithKline, Novartis, Grifols, Sanofi, Takeda, Covis, Valeo, Lung Association of Saskatchewan, Canadian Thoracic Society, Lung Association of Alberta and Northwest Territories; leadership roles with Canadian Thoracic Society and Alberta Health Services; Canadian Thoracic Society Executive Committee, Co-Chair of the CTS COPD Clinical Assembly; Chair of the Royal College of Physicians and Surgeons Adult Respiratory Examination. J Bourbeau reports grants from McGill University, the McGill University Health Centre Foundation, the Canadian Institute Health Research, Grifols, Novartis, Sanofi, and the Respiratory Health Network of the Fonds de la recherche en santé du Québec; grants and personal fees (honoraria) from Astra Zeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, and Trudell Canada Ltd; and personal fees (honoraria) from Pfizer Canada Ltd, and COVIS Pharma Canada Ltd, outside the submitted work. SG Goodman reports research grant support (eg, steering committee or data and safety monitoring committee) and/or speaker/consulting honoraria (eg, advisory boards) from: Amgen, Alnylam, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, CYTE Ltd., Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, Idorsia, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Roche, Sanofi, Servier, Tolmar Pharmaceuticals, Valeo Pharma; and salary support/honoraria from the Canadian Heart Failure Society, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, Jewish General Hospital\ CIUSSS Centre-Ouest-de-l’Ile-de-Montreal, Peter Munk Cardiac Centre Clinical Trials and Translation Unit, Ted Rogers Centre for Heart Research, New York University Clinical Coordinating Centre, PERFUSE Research Institute, TIMI Study Group (Brigham Health). NM Hawkins reports research grant support, served on advisory boards for, or speaker engagements with AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Servier. AG Kaplan reports consulting fees or honoraria from AstraZeneca, ALK, Bellus, BI, Covis, Cipla, Eisai, GSK, Merck Frosst, Metapharm, Moderna, Novo Nordisk, Pfizer Sanofi, Teva, Trudell, Valeo; Chairperson of Family Physician Airways Group of Canada; Vice president of Respiratory Effectiveness Group. AGK is an honorary professor of primary care Respiratory Research, Observational and Pragmatic Research Institute; Medical director, local pulmonary rehabilitation program; Board member, Thrombosis Canada; Senate member of the International Primary Care Respiratory Group. P Lin reports speaker honorarium for CME events from AstraZeneca, GlaxoSmithKline, Medexus, Moderna, Pfizer, Amgen, Novo Nordisk, Boehringer-Ingelheim, and Eli Lilly. ED Penz reports consulting fees, support for travel, or honoraria from AstraZeneca, GlaxoSmithKline, Sanofi, Covis, LungSask, Canadian Thoracic Society, Valeo; research funds from CIHR, Saskatchewan Health Research Foundation, Respiratory Research Center, LungSask, Saskatchewan Centre for Patient oriented research, and AstraZeneca. She reports contract with Saskatchewan Cancer Agency for her role as medical advisor for the Saskatchewan Lung Screening program, board member of Institute of Cancer Research Advisory Board (CIHR), Canadian Thoracic Society Executive Committee, and Past Co-Chair of the CTS COPD Clinical Assembly. S Verma holds a Tier 1 Canada Research Chair in Cardiovascular Surgery, and reports receiving research grants and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, Pfizer, PhaseBio, S & L Solutions Event Management Inc, and Sanofi. He is the President of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organization. S Zieroth reports research grant support, served on advisory boards for, or speaker engagements with AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Eli Lilly, GSK, Janssen, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Servier and Vifor Pharma; and serves on a clinical trial committee or as a national lead for studies sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, and Pfizer. The authors report no other conflicts of interest in this work., (© 2024 Bhutani et al.)

Background: Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI)., Objectives: This study sought to evaluate the association of left ventricular ejection fraction (LVEF), congestion, or both, with outcomes and the impact of empagliflozin in reducing HF risk post-AMI., Methods: In the EMPACT-MI (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) trial, patients were randomized within 14 days of an AMI complicated by either newly reduced LVEF<45%, congestion, or both, to empagliflozin (10 mg daily) or placebo and were followed up for a median of 17.9 months., Results: Among 6,522 patients, the mean baseline LVEF was 41 ± 9%; 2,648 patients (40.6%) presented with LVEF <45% alone, 1,483 (22.7%) presented with congestion alone, and 2,181 (33.4%) presented with both. Among patients in the placebo arm of the trial, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (HR: 1.49; 95% CI: 1.31-1.69; P < 0.0001), first HF hospitalization (HR: 1.64; 95% CI: 1.37-1.96; P < 0.0001), and total HF hospitalizations (rate ratio [RR]: 1.89; 95% CI: 1.51-2.36; P < 0.0001). The presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR: 1.52, 1.94, and RR: 2.03, respectively). Empagliflozin reduced the risk for first (HR: 0.77; 95% CI: 0.60-0.98) and total (RR: 0.67; 95% CI: 0.50-0.89) HF hospitalizations, irrespective of LVEF or congestion, or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status., Conclusions: In patients with AMI, the severity of left ventricular dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion. (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction [EMPACT-MI]; NCT04509674)., Competing Interests: Funding Support and Author Disclosures Funding support was provided by Boehringer Ingelheim and Eli Lilly and Company. Dr Udell has served on the advisory boards of Boehringer Ingelheim, Novavax, Novo Nordisk, and Sanofi; has received speaker honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly; and has received research funding to his institution from Amgen, Bayer, Boehringer Ingelheim, and Novartis. Dr Petrie has received research funding from Boehringer Ingelheim, Roche, SQ Innovations, AstraZeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, and Pharmacosmos; and has served as a consultant and on trial committees for Akero, Applied Therapeutics, Amgen, AnaCardio, Biosensors, Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, AbbVie, Bayer, Horizon Therapeutics, Takeda, Cardiorentis, Pharmacosmos, Siemens, Eli Lilly, Vifor, New Amsterdam, Moderna, Teikoku, LIB Therapeutics, and 3R Lifesciences. Dr Jones has received research grants from Bayer, Boehringer Ingelheim, Merck, Novartis, PCORI, and the National Institutes of Health (NIH). Dr Mattheus is an employee of Boehringer Ingelheim. Dr Seide is an employee of Boehringer Ingelheim. Dr Amir has served as a national principal investigator and as a steering committee member for the study; has participated in paid lectures and advisory board meetings and has clinical trials with Boehringer Ingelheim. Dr Bahit has received modest honoraria from MSD, Pfizer, Bristol Myers Squibb, CSL Behring, Janssen, Boehringer Ingelheim, and Anthos Therapeutics. Dr Bauersachs has received honoraria for lectures or consulting from Novartis, Vifor, Bayer, Pfizer, Boehringer Ingelheim, AstraZeneca, Cardior, CVRx, BMS, Amgen, Corvia, Norgine, Edwards Lifesciences, and Roche, unrelated to this work; and has received research support for the department from Zoll, CVRx, Abiomed, Norgine, and Roche, unrelated to this work. Dr Bayes-Genis has lectured and/or participated in advisory boards for Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Novo Nordisk, Roche, and Vifor. Dr Goodman has received research grant support (steering committee or data and safety monitoring committee) and/or speaker or consulting honoraria (advisory boards) from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, CYTE Ltd, Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, Idorsia, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, Servier, Tolmar Pharmaceuticals, and Valeo Pharma; and has received salary support or honoraria from the Canadian Heart Failure Society, Canadian Heart Research Centre, and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Center for Clinical Research, Duke Clinical Research Institute, Jewish General Hospital, New York University Clinical Coordinating Centre, PERFUSE Research Institute, Peter Munk Cardiac Centre Clinical Trials and Translation Unit, and the TIMI Study Group (Brigham Health). Dr Goto has served on the advisory boards of Antos Therapeutic and Janssen; and has received honoraria from the American Heart Association (Associate Editor); and has served on the grant evaluation committee for the Nakatani Foundation and the Kaketsuken Foundation. Dr Gasior is an employee of Boehringer Ingelheim. Dr Jamal is an employee of Boehringer Ingelheim. Dr Januzzi has served as a trustee of the American College of Cardiology; has served as a board member of Imbria Pharmaceuticals; has served as director at Jana Care; has received research support from Abbott, Applied Therapeutics, Bayer, Bristol Myers Squibb, HeartFlow, Innolife, Medtronic, and Roche; has received consulting income from Abbott, AstraZeneca, Bayer, Beckman, Boehringer Ingelheim, Cytokinetics, Janssen, Merck, Novartis, Prevencio, Quidel/Ortho, and Roche; and has participated in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Axon, Bayer, CVRx, Medtronic, Pfizer, Roche, and Takeda. Dr Lopes has received research grants or contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi; has received funding for educational activities or lectures from Pfizer, Daiichi-Sankyo, and Novo Nordisk; and has received funding for consulting or other services from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Novo Nordisk. Dr Martinez-Traba is an employee of Boehringer Ingelheim. Dr Parikh has served as a consultant for Medtronic; and has received institutional research grants from Abbott and Edwards Lifesciences. Dr Parkhomenko has received research grants and personal fees from Bayer, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squib/Pfizer, and Daiichi-Sankyo. Dr Schou has received lecture fees from Novartis, AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr van der Meer has received grant support from the European Research Council (ERC CoG 101045236, DISSECT-HF) and the University Medical Centre Groningen; and Dr van der Meer’s employer, has received consultancy fees and/or grants from Novartis, Pharmacosmos, Vifor Pharma, AstraZeneca, Pfizer, Pharma Nord, BridgeBio, Novo Nordisk, Daiichi-Sankyo, Boehringer Ingelheim, and Ionis. Dr Vinereanu has received research grants and consultancy fees from Boehringer Ingelheim; and has received research grants from Bayer Healthcare, Novartis, and Servier. Dr Zieroth has received research grant support, served on advisory boards for, or participated in speaker engagements with AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Cytokinetics, Eli Lilly, GSK, Janssen, Medtronic, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, Salubrisbio, Servier, and Vifor Pharma; has served on a clinical trial committee or as a national lead for studies sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, and Pfizer; and has nonindustry relationships with the Canadian Medical and Surgical KT Group, CCS, CHFS, Charite, EOCI, Liv, Medscape, Ology, PACE-CME, Radcliffe, Reach MD, and the Translational Medicine Academy. Dr Brueckmann is an employee of Boehringer Ingelheim. Dr Sumin is an employee of Boehringer Ingelheim. Dr Bhatt has served on the advisory boards of Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; has served on the Board of Directors of the American Heart Association New York City, Angiowave (with stock options), Bristol Myers Squibb (with stock), DRS.LINQ (with stock options), and High Enroll (with stock); has served as a consultant for Broadview Ventures, GlaxoSmithKline, Hims, SFJ, and Youngene; has served on data monitoring committees for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute; and Rutgers University (for the NIH-funded MINT Trial); has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (American Heart Association lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee); has served as Deputy Editor for Clinical Cardiology; has been named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital, which assigned it to Lexicon; neither Dr Bhatt nor Brigham and Women’s Hospital receives any income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Eli Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; has received royalties from Elsevier (Editor, Braunwald’s Heart Disease); has served as site co-investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; has served as a trustee of the American College of Cardiology; and has conducted unfunded research for FlowCo. Dr Hernandez has served as a consultant to Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cytokinetics, Eidos, GlaxoSmithKline, Intellia, Intercept, Myokardia, Novartis, Novo Nordisk, Prolaio, and TikkunLev; and has received research funding from American Regent, Amgen, Bayer, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Novo Nordisk, and Verily. Dr Butler has served as a consultant for Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Bearing, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Lexicon, Eli Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Regeneron, Renibus, Roche, Salamandra, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: To describe the baseline characteristics of participants in the FINEARTS-HF trial, contextualized with prior trials including patients with heart failure (HF) with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF). The FINEARTS-HF trial is comparing the effects of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo in reducing cardiovascular death and total worsening HF events in patients with HFmrEF/HFpEF., Methods and Results: Patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≥40%, estimated glomerular filtration rate ≥ 25 ml/min/1.73 m 2 , elevated natriuretic peptide levels and evidence of structural heart disease were enrolled and randomized to finerenone titrated to a maximum of 40 mg once daily or matching placebo. We validly randomized 6001 patients to finerenone or placebo (mean age 72 ± 10 years, 46% women). The majority were New York Heart Association functional class II (69%). The baseline mean LVEF was 53 ± 8% (range 34-84%); 36% of participants had a LVEF <50% and 64% had a LVEF ≥50%. The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 1041 (interquartile range 449-1946) pg/ml. A total of 1219 (20%) patients were enrolled during or within 7 days of a worsening HF event, and 3247 (54%) patients were enrolled within 3 months of a worsening HF event. Compared with prior large-scale HFmrEF/HFpEF trials, FINEARTS-HF participants were more likely to have recent (within 6 months) HF hospitalization and greater symptoms and functional limitations. Further, concomitant medications included a larger percentage of sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors than previous trials., Conclusions: FINEARTS-HF has enrolled a broad range of high-risk patients with HFmrEF and HFpEF. The trial will determine the safety and efficacy of finerenone in this population., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Cardiovascular disease has been the leading cause of death in the United States and Canada for decades. Although it affects millions of people across a multitude of backgrounds, notable disparities in cardiovascular health are observed among women and become more apparent when accounting for race and socioeconomic status. Although intrinsic sex-specific physiologic differences predispose women to poorer outcomes, social determinants of health (SDOH) and biases at both the individual provider and the larger health care system levels play an equal, if not greater, role. This review examines socioeconomic disparities in women compared with men regarding cardiovascular risk factors, treatments, and outcomes. Although various at-risk subpopulations exist, we highlight the impact of SDOH in specific populations, including patients with disabilities, transgender persons, and South Asian and Indigenous populations. These groups are underrepresented in studies and experience poorer health outcomes owing to structural barriers to care. These findings emphasise the significance of understanding the interplay of different socioeconomic factors and how their stacking can negatively affect women's cardiovascular health. To address these disparities, we propose a multipronged approach to augment culturally sensitive and patient-centred care. This includes increased cardiovascular workforce diversity, inclusion of underrepresented populations into analyses of cardiovascular metrics, and greater utilisation of technology and telemedicine to improve access to health care. Achieving this goal will necessitate active participation from patients, health care administrators, physicians, and policy makers, and is imperative in closing the cardiovascular health gap for women over the coming decades., (Copyright © 2024 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Empagliflozin reduces the risk of heart failure (HF) events in patients with type 2 diabetes at high cardiovascular risk, chronic kidney disease, or prevalent HF irrespective of ejection fraction. Whereas the EMPACT-MI trial (Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients With Acute Myocardial Infarction) showed that empagliflozin does not reduce the risk of the composite of hospitalization for HF and all-cause death, the effect of empagliflozin on first and recurrent HF events after myocardial infarction is unknown., Methods: EMPACT-MI was a double-blind, randomized, placebo-controlled, event-driven trial that randomized 6522 patients hospitalized for acute myocardial infarction at risk for HF on the basis of newly developed left ventricular ejection fraction of <45% or signs or symptoms of congestion to receive empagliflozin 10 mg daily or placebo within 14 days of admission. In prespecified secondary analyses, treatment groups were analyzed for HF outcomes., Results: Over a median follow-up of 17.9 months, the risk for first HF hospitalization and total HF hospitalizations was significantly lower in the empagliflozin compared with the placebo group (118 [3.6%] versus 153 [4.7%] patients with events; hazard ratio, 0.77 [95% CI, 0.60, 0.98]; P =0.031, for first HF hospitalization; 148 versus 207 events; rate ratio, 0.67 [95% CI, 0.51, 0.89]; P =0.006, for total HF hospitalizations). Subgroup analysis showed consistency of empagliflozin benefit across clinically relevant patient subgroups for first and total HF hospitalizations. The need for new use of diuretics, renin-angiotensin modulators, or mineralocorticoid receptor antagonists after discharge was less in patients randomized to empagliflozin versus placebo (all P <0.05)., Conclusions: Empagliflozin reduced the risk of HF in patients with left ventricular dysfunction or congestion after acute myocardial infarction., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04509674., Competing Interests: Disclosures Dr Hernandez has served as a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cytokinetics, Eidos, GlaxoSmithKline, Intellia, Intercept, MyoKardia, Novartis, Novo Nordisk, Prolaio, and TikkunLev; and has received research funding from American Regent, Amgen, Bayer, Boehringer Ingelheim, Lilly, Merck, Novartis, Novo Nordisk, and Verily. Dr Bhatt has served on advisory boards for ANGIOWave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Stasys; on the board of directors for American Heart Association New York City, ANGIOWave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); has served as a consultant for Broadview Ventures, GlaxoSmithKline, Hims, SFJ, and Youngene; has served on data monitoring committees for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic, Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute, and Rutgers University (for the NIH-funded MINT Trial); has received honoraria from American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; chair, ACC accreditation oversight committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor-in-chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor-in-chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest editor; associate editor), K2P (co-chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), and Wiley (steering committee); other: Clinical Cardiology (deputy editor); is named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital, which was assigned to Lexicon (neither Dr Bhatt nor Brigham and Women’s Hospital receives any income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; has received royalties from Elsevier (editor, Braunwald’s Heart Disease); has served as site coinvestigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; has served as trustee for American College of Cardiology; and performed unfunded research for FlowCo. Dr Butler has served as a consultant to Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Bearing, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Lexicon, Lilly, LivaNova, Janssen, Medtronic, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Regeneron, Renibus, Roche, Salamandra, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. Dr Goto reports serving as Associate Editor for Circulation and receipt of a steering committee fee from the Duke Clinical Research Institute for EMPACT-MI. Dr Lopes reports research grants or contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi-Aventis; funding for educational activities or lectures from Pfizer, Daiichi Sankyo, and Novo Nordisk; and funding for consulting or other services from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Novo Nordisk. Dr Amir reports serving as National PI-Steering committee member for the study and participated in paid lectures and advisory board meetings and clinical trials in Dr Amir’s department at Boehringer Ingelheim. Dr Beyes-Genis has lectured or participated in advisory boards for Abbott, AstraZeneca, Bayer, Boehringer-Ingelheim, Medtronic, Novartis, Novo Nordisk, Roche Diagnostics, and Vifor. Dr Bahit reports modest honorarium from MSD, Pfizer, Bristol Myers Squibb, CSL Behring, Janssen, Boehringer Ingelheim, and Anthos Therapeutics. Dr Bauersachs received honoraria for lectures/consulting from Novartis, Vifor, Bayer, Pfizer, Boehringer Ingelheim, AstraZeneca, Cardior, CVRx, BMS, Amgen, Corvia, Norgine, Edwards, and Roche not related to this article; and research support for Dr Bauersachs’ department from Zoll, CVRx, Abiomed, Norgine, and Roche, not related to this article. Dr Schou reports lecture fees from Novartis, Astra Zeneca, Bohringer, and Novo Nordisk. Dr Steg reports research grants from Amarin and Sanofi; clinical trial participation for Amarin, Amgen, AstraZeneca, Idorsia, Janssen, Novartis, Novo-Nordisk, and Sanofi; consulting or speaking for Amarin, Amgen, and Novo-Nordisk; and serving as senior associate editor at Circulation. Dr Parikh reports serving as a consultant for Medtronic, Inc and receipt of an institutional research grant from Abbott and Edwards Lifesciences. Dr Januzzi reports participation as a trustee of the American College of Cardiology, board member of Imbria Pharmaceuticals, and director at Jana Care; has received research support from Abbott, Applied Therapeutics, Bayer, BBMS, HeartFlow Inc, Innolife, and Roche Diagnostics, and consulting income from Abbott, AstraZeneca, Bayer, Beckman, Boehringer-Ingelheim, Janssen, Medtronic, Novartis, Prevencio, Quidel/Ortho, Roche Diagnostics, and Vascular Dynamics; and participates in clinical end point committees or data safety monitoring boards for Abbott, AbbVie, Bayer, CVRx, Medtronic, Pfizer, Roche Diagnostics, and Takeda. Dr Goodman reports research grant support (eg, steering committee or data and safety monitoring committee) or speaker or consulting honoraria (eg, advisory boards) from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, CYTE Ltd, Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, Idorsia, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, Servier, Tolmar Pharmaceuticals, and Valeo Pharma; and salary support or honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) Chair, Canadian Heart Failure Society, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating Centre, PERFUSE Research Institute, and TIMI Study Group (Brigham Health). Dr van der Meer reports support from the European Research Council (ERC CoG 101045236, DISSECT-HF); the UMCG, which employs Dr van der Meer, received consultancy fees or grants from Novartis, Pharmacosmos, Vifor Pharma, Astra Zeneca, Pfizer, Pharma Nord, BridgeBio, Novo Nordisk, Daiichi Sankyo, Boehringer Ingelheim, and Ionis. Dr Petrie reports research funding from Boehringer Ingelheim, Roche, SQ Innovations, Astra Zeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, and Pharmacosmos; and consultancy or trial committee participation from Akero, Applied Therapeutics, Amgen, AnaCardio, Biosensors, Boehringer Ingelheim, Novartis, Astra Zeneca, Novo Nordisk, AbbVie, Bayer, Horizon Therapeutics, Takeda, Cardiorentis, Pharmacosmos, Siemens, Eli Lilly, Vifor, New Amsterdam, Moderna, Teikoku, LIB Therapeutics, and 3R Lifesciences. Dr Parkhomenko reports research grants and personal fees from Bayer, Amgen, Astra Zeneca, Boehringer Ingelheim, BMS/Pfizer, and Daiichi-Sankyo. Dr Vinereanu reports research grants and consultancy fees from Boehringer Ingelheim and research grants from Bayer Healthcare, Novartis, and Servier Pharmaceuticals LLC. Dr Zieroth reports research grant support, served on advisory boards for, or had speaker engagements with AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Eli Lilly, GSK, Janssen, Medtronic, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, Salubrisbio, Servier, and Vifor Pharma; and serves on a clinical trial committee or as a national lead for studies sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis and Pfizer; nonindustry participation includes Canadian Medical and Surgical KT Group, CCS, CHFS, Charite, EOCI, Liv, Medscape, Ology, PACE-CME, Radcliffe, Reach MD, and Translational Medicine Academy. Dr Jones reports research grants from Bayer, Boehringer Ingelheim, Merck, Novartis, PCORI, and the National Institutes of Health. Drs Seide, Mattheus, Zwiener, Sumin, Gasior, Jamal, and Brueckmann are employees of Boehringer Ingelheim.

Background: Decompensated heart failure (HF) can be categorized as de novo or worsening of chronic HF. In PARAGLIDE-HF (Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF), among patients with an ejection fraction >40% that stabilized after worsening HF, sacubitril/valsartan led to a significantly greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and was associated with clinical benefit compared to valsartan., Objectives: This prespecified analysis characterized patients with de novo vs worsening chronic HF in PARAGLIDE-HF and assessed the interaction between HF chronicity and the effect of sacubitril/valsartan., Methods: Patients were classified as de novo (first diagnosis of HF) or chronic (known HF prior to the index event). Time-averaged proportional change in NT-proBNP from baseline to weeks 4 and 8 was analyzed using an analysis of covariance model. A win ratio consisting of time to cardiovascular death, number and times of HF hospitalizations during follow-up, number and times of urgent HF visits during follow-up, and time-averaged proportional change in NT-proBNP was assessed for each group., Results: Of the 466 participants, 153 (33%) had de novo HF and 313 (67%) had chronic HF. De novo patients had lower rates of atrial fibrillation/flutter and lower creatinine. There was a nonsignificant reduction in NT-proBNP with sacubitril/valsartan vs valsartan for de novo (0.82; 95% CI: 0.62-1.07) and chronic HF (0.88; 95% CI: 0.73-1.07), interaction P  = 0.66. The win ratio was nominally in favor of sacubitril/valsartan for both de novo (1.12; 95% CI: 0.70-1.58) and chronic HF (1.24; 95% CI: 0.89-1.71)., Conclusions: There is no interaction between HF chronicity and the effect of sacubitril-valsartan., Competing Interests: PARAGLIDE-HF was funded by Novartis Pharmaceuticals Corporation. Dr Mentz has received research support and/or honoraria from Novartis, Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Medable, Merck, Novo Nordisk, Pharmacosmos, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. Drs Ward and Williamson are employees of Novartis. Dr Hernandez has received research grants from American Regent, Amgen, AstraZeneca, Bayer, Bayer, Boehringer Ingelheim, Cytokinetics, Merck, Novartis, Somologic, and Verily, and has served as a consultant for Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Merck, Novartis, and Novo Nordisk. Dr Morrow is a member of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc, AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc, Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc, Janssen Research and Development, LLC, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Inc, Roche, Siemens Healthcare Diagnostics, Inc, Softcell Medical Limited, and Zora Biosciences, and has received consulting fees from Abbott Laboratories, ARCA Biopharma, Inflammatix, Merck and Co, Novartis, and Roche Diagnostics. Dr Starling serves on the steering committee for the PARAGLIDE trial sponsored by Novartis. Dr Desai has received research grants (to Brigham and Women’s Hospital) from Abbott, Alnylam, AstraZeneca, Bayer, and Novartis; and has received personal consulting fees from Abbott, Alnylam, AstraZeneca, Avidity Biopharma, Axon Therapeutics, Bayer, Biofourmis, Cytokinetics, GlaxoSmithKline, Medpace, Merck, New Amsterdam, Novartis, Parexel, Regeneron, River2Renal, Roche, Verily, and Veristat. Dr Zieroth has received research grant support, served on advisory boards for, or has had speaker engagements with Abbott, Akcea AstraZeneca, Amgen, Alnylam, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, Servier, and Vifor Pharma; and serves on a clinical trial committee or as a national lead for studies sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, and Pfizer. Dr Solomon has received research grants from Alnylam, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Cytokinetics, Eidos, GlaxoSmithKline, Ionis, Lilly, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, Actelion, Amgen, Bellerophon, Celladon, Gilead, Mesoblast, Neurotronik, and US2; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: A recent study showed that the accuracy of heart failure (HF) cardiologists and family doctors to predict mortality in outpatients with HF proved suboptimal, performing less well than models., Objectives: The authors sought to evaluate patient and physician factors associated with physician accuracy., Methods: The authors included outpatients with HF from 11 HF clinics. Family doctors and HF cardiologists estimated patient 1-year mortality. They calculated predicted mortality using the Seattle HF Model and followed patients for 1 year to record mortality (or urgent heart transplant or ventricular assist device implant as mortality-equivalent events). Using multivariable logistic regression, the authors evaluated associations among physician experience and confidence in estimates, duration of patient-physician relationship, patient-physician sex concordance, patient race, and predicted risk, with concordant results between physician and model predictions., Results: Among 1,643 patients, 1-year event rate was 10% (95% CI: 8%-12%). One-half of the estimates showed discrepant results between model and physician predictions, mainly owing to physician risk overestimation. Discrepancies were more frequent with increasing patient risk from 38% in low-risk to ∼75% in high-risk patients. When making predictions on male patients, female HF cardiologists were 26% more likely to have discrepant predictions (OR: 0.74; 95% CI: 0.58-0.94). HF cardiologist estimates in Black patients were 33% more likely to be discrepant (OR: 0.67; 95% CI: 0.45-0.99). Low confidence in predictions was associated with discrepancy. Analyses restricted to high-confidence estimates showed inferior calibration to the model, with risk overestimation across risk groups., Conclusions: Discrepant physician and model predictions were more frequent in cases with perceived increased risk. Model predictions outperform physicians even when they are confident in their predictions. (Predicted Prognosis in Heart Failure [INTUITION]; NCT04009798)., Competing Interests: Funding Support and Author Disclosures This study received funding from a Grant-in-Aid offered by the Heart and Stroke Foundation of Canada. Dr Alba has received funding by the Heart and Stroke Foundation of Canada Clinician-Scientist Program. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Empagliflozin improves cardiovascular outcomes in patients with heart failure, patients with type 2 diabetes who are at high cardiovascular risk, and patients with chronic kidney disease. The safety and efficacy of empagliflozin in patients who have had acute myocardial infarction are unknown., Methods: In this event-driven, double-blind, randomized, placebo-controlled trial, we assigned, in a 1:1 ratio, patients who had been hospitalized for acute myocardial infarction and were at risk for heart failure to receive empagliflozin at a dose of 10 mg daily or placebo in addition to standard care within 14 days after admission. The primary end point was a composite of hospitalization for heart failure or death from any cause as assessed in a time-to-first-event analysis., Results: A total of 3260 patients were assigned to receive empagliflozin and 3262 to receive placebo. During a median follow-up of 17.9 months, a first hospitalization for heart failure or death from any cause occurred in 267 patients (8.2%) in the empagliflozin group and in 298 patients (9.1%) in the placebo group, with incidence rates of 5.9 and 6.6 events, respectively, per 100 patient-years (hazard ratio, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P = 0.21). With respect to the individual components of the primary end point, a first hospitalization for heart failure occurred in 118 patients (3.6%) in the empagliflozin group and in 153 patients (4.7%) in the placebo group (hazard ratio, 0.77; 95% CI, 0.60 to 0.98), and death from any cause occurred in 169 (5.2%) and 178 (5.5%), respectively (hazard ratio, 0.96; 95% CI, 0.78 to 1.19). Adverse events were consistent with the known safety profile of empagliflozin and were similar in the two trial groups., Conclusions: Among patients at increased risk for heart failure after acute myocardial infarction, treatment with empagliflozin did not lead to a significantly lower risk of a first hospitalization for heart failure or death from any cause than placebo. (Funded by Boehringer Ingelheim and Eli Lilly; EMPACT-MI ClinicalTrials.gov number, NCT04509674.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: The efficacy and safety of sacubitril/valsartan in patients hospitalized with heart failure (HF) across the spectrum of left ventricular ejection fraction (EF) has not been described., Objectives: Data from randomized trials of sacubitril/valsartan in HF patients with EF ≤40% (PIONEER-HF [Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode] trial) and >40% (PARAGLIDE-HF [Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF] trial) following recent worsening heart failure (WHF) were pooled to examine treatment effect across the EF spectrum., Methods: The PIONEER-HF and PARAGLIDE-HF trials were double-blind, randomized trials of sacubitril/valsartan vs control therapy (enalapril or valsartan, respectively). All participants in the PIONEER-HF trial and 69.5% in the PARAGLIDE-HF trial were enrolled during hospitalization for HF after stabilization. The remainder in the PARAGLIDE-HF trial were enrolled ≤30 days after a WHF event. The primary endpoint of both trials was time-averaged proportional change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8. Adjudicated clinical endpoints were analyzed through the end of follow-up, adjusting for trial., Results: The pooled analysis included 1,347 patients (881 from PIONEER-HF, 466 from PARAGLIDE-HF). Baseline characteristics included median age 66 years, 36% women, 31% Black, 34% de novo HF, and median EF 30%. The reduction in NT-proBNP was 24% greater with sacubitril/valsartan vs control therapy (n = 1,130; ratio of change = 0.76; 95% CI: 0.69-0.83; P < 0.0001). Cardiovascular death or hospitalization for HF was reduced by 30% with sacubitril/valsartan vs control therapy (HR: 0.70; 95% CI: 0.54-0.91; P = 0.0077). This effect was consistent across the spectrum of EF ≤60%. Sacubitril/valsartan increased symptomatic hypotension (risk ratio: 1.35; 95% CI: 1.05-1.72)., Conclusions: In patients stabilized after WHF, sacubitril/valsartan led to a greater reduction in plasma NT-proBNP and improved clinical outcome compared with control therapy, in particular across the spectrum of EF ≤60%. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890; Changes in NT-proBNP, Safety, and Tolerability in HFpEF Patients With a WHF Event [HFpEF Decompensation] Who Have Been Stabilized and Initiated at the Time of or Within 30 Days Post-decompensation [PARAGLIDE-HF]; NCT03988634)., Competing Interests: Funding Support and Author Disclosures The PIONEER-HF and PARAGLIDE-HF trials were supported by Novartis Pharmaceuticals Corp. Drs Morrow and Park are members of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Janssen Research and Development, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Roche, Siemens Healthcare Diagnostics, Softcell Medical Limited, and Zora Biosciences. Dr Morrow has received consulting fees from Abbott Laboratories, ARCA Biopharma, Inflammatix, Merck and Co, Novartis, Regeneron, and Roche Diagnostics. Dr Velazquez has received institutional research grant support and/or honoraria for serving on advisory boards from Novartis, Abiomed, Rednvia, and the National Heart, Lung, and Blood Institute/National Institutes of Health. Dr Desai has received research grants (to Brigham and Women’s Hospital) from Abbott, Alnylam, AstraZeneca, Bayer, and Novartis; and has received personal consulting fees from Abbott, Alnylam, AstraZeneca, Avidity Biopharma, Axon Therapeutics, Bayer, Biofourmis, Cytokinetics, GlaxoSmithKline, Medpace, Merck, New Amsterdam, Novartis, Parexel, Regeneron, River2Renal, Roche, Verily, and Veristat. Dr DeVore has received research funding through his institution from Biofourmis, Bodyport, Cytokinetics, American Regent, Inc, the National Institutes of Health and National Heart, Lung, and Blood Institute, Novartis, and Story Health; and has served as a consultant for and/or received honoraria from Abiomed, Cardionomic, LivaNova, Natera, Novo Nordisk, Story Health, and Zoll. Dr Sharma has served on the advisory board and/or as a consultant for Alleviant, AstraZeneca, Bayer, Boehringer Ingelheim, Edwards Lifesciences, Imbria, Novartis, Novo Nordisk, RIVUS, and ViCardia. Dr Solomon has received research grants from Alnylam, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Cytokinetics, Eidos, GlaxoSmithKline, Ionis, Lilly, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, Actelion, Amgen, Bellerophon, Celladon, Gilead, Mesoblast, Neurotronik, and US2; and has served as a consultant for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, MyoKardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. Dr Starling has served on the steering committee for the PARAGLIDE trial sponsored by Novartis and for the RESPONDER HF trial sponsored by Corvia Medical. Drs Ward and Williamson are employees of Novartis. Dr Zieroth has received research grant support from, served on advisory boards for, or served as a speaker for Abbott, Akcea AstraZeneca, Amgen, Alnylam, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, Servier, and Vifor Pharma; and has served on a clinical trial committee or as a national lead for studies sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, and Pfizer. Dr Hernandez has received research grants from American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Merck, Novartis, Novo Nordisk, Somologic, and Verily; and has served as a consultant for Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Intellia, Merck, Novartis, and Novo Nordisk. Dr Mentz has received research support and/or honoraria from Novartis, Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Medable, Merck, Novo Nordisk, Pharmacosmos, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. Dr Braunwald has received grant support to his institution from Novartis for the conduct of the PIONEER-HF trial, for serving on the Executive Committee of the PARADISE-MI trial and the Steering Committee of the PARAGLIDE-HF trial, and for participation in an advisory board meeting; and has served as a consultant for Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Cardurion, Edgewise, and Verve. Dr Lepage has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Exposure to ionizing radiation is an inherent occupational health hazard in clinical cardiology. Health risks have been reported previously, including predilection to cancer. In addition, orthopedic injury due to prolonged wearing of heavy protective lead aprons, which are mandatory to reduce radiation risk, have been extensively documented. Cardiology as a specialty has grown with rising volumes of increasingly complex procedures. This includes electrophysiological, coronary, and structural intervention, advanced heart failure/transplant management, and diagnostic imaging. Both the operator as well imaging specialists are exposed to radiation, particularly in structural interventions where interventional cardiologists and structural imagers work closely. Increasingly, women interested in cardiology may deselect the field due to radiation concerns. This expert document highlights the risks of radiation exposure in cardiology, including practical tips within various subspecialty fields such as interventional/structural cardiology, electrophysiology, imaging, advanced heart failure, and pediatric cardiology., Competing Interests: Dr Zieroth has received research grant support, served on advisory boards for, or speaker engagements with AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Eli Lilly, GSK, Janssen, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Servier, and Vifor Pharma; and serves on a clinical trial committee or as a national lead for studies sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis and Pfizer. Nonindustray support was received by Canadian Medical and Surgical KT Group, CCS, CHFS, Charite, EOCI, Liv, Medscape, Ology, PHRI, PACE-CME, Radcliffe, Translational Medicine Academy. Dr Dalal is a speaker for Medtronic. Dr Razminia is related to Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: The 2022 Canadian Cardiovascular Society (CCS) cardiorenal guideline provided clinical recommendations on sodium-glucose co-transport 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) use. Since then, additional trials of relevance for SGLT2i have been published. This update re-evaluates the clinical recommendations for using SGLTi and their indirect comparison with existing evidence on GLP-1RA as compared to the standard of care to reduce cardiorenal morbidity and mortality., Methods: We updated our existing search and screening of the literature from September 2021 to April 2023 for randomized controlled trials of SGLT2i and GLP-1RA with placebo control. We conducted risk of bias assessment, data extraction and updated our meta-analysis of studies with similar interventions and components. The certainty of the evidence was determined using GRADE., Results: Evidence from three new trials and additional results from an updated existing trial on SGLT2i met our inclusion criteria after an updated search. Across all the included studies, the total sample size was 151,023 adults, with 90,943 in SGLT2i trials and 60,080 in GLP-1 RA trials. The mean age ranged from 59.9 to 68.4 years. Compared with standard care, the use of SGLT2i and GLP-1 RA showed significant reductions in the outcomes of cardiovascular (CV) mortality (14% & 13%), any-cause mortality (12% & 12%), major adverse CV events (MACE) (11% & 14%), heart failure (HF) hospitalization (30% & 9%), CV death or HF hospitalization (23% & 11%), and kidney composite outcome (32% & 22%). In participants with T2D, both classes demonstrated significant cardiorenal protection. But, only GLP-1RA showed a reduction in non-fatal stroke (16%) and only SGLT2i showed a reduction in HF hospitalization (30%) in this population of people living with T2D., Conclusions: This updated and comprehensive meta-analysis substantiates and strengthens the clinical recommendations of the CCS cardiorenal guidelines., (© 2024. The Author(s).)

There is waning interest among cardiology trainees in pursuing an Advanced Heart Failure/Transplant Cardiology (AHFTC) fellowship as evidenced by fewer applicants in the National Resident Matching Program match to this specialty. This trend has generated considerable attention across the heart failure community. In response, the Heart Failure Society of America convened the AHFTC Fellowship Task Force with a charge to develop strategies to increase the value proposition of an AHFTC fellowship. Subsequently, the HFSA sponsored the AHFTC Fellowship Consensus Conference April 26-27, 2023. Before the conference, interviews of 44 expert stakeholders diverse across geography, site of practice (traditional academic medical center or other centers), specialty/area of expertise, sex, and stage of career were conducted virtually. Based on these interviews, potential solutions to address the declining interest in AHFTC fellowship were categorized into five themes: (1) alternative training pathways, (2) regulatory and compensation, (3) educational improvements, (4) exposure and marketing for pipeline development, and (5) quality of life and mental health. These themes provided structure to the deliberations of the AHFTC Fellowship Consensus Conference. The recommendations from the Consensus Conference were subsequently presented to the HFSA Board of Directors to inform strategic plans and interventions. The HFSA Board of Directors later reviewed and approved submission of this document. The purpose of this communication is to provide the HF community with an update summarizing the processes used and concepts that emerged from the work of the HFSA AHFTC Fellowship Task Force and Consensus Conference., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Heart failure (HF) is the leading cause of mortality in patients with acute myocardial infarction (AMI), with incidence ranging from 14% to 36% in patients admitted due to AMI. HF post-MI develops due to complex inter-play between macrovascular obstruction, microvascular dysfunction, myocardial stunning and remodeling, inflammation, and neuro-hormonal activation. Cardiogenic shock is an extreme presentation of HF post-MI and is associated with a high mortality. Early revascularization is the only therapy shown to improve survival in patients with cardiogenic shock. Treatment of HF post-MI requires prompt recognition and timely introduction of guideline-directed therapies to improve mortality and morbidity. This article aims to provide an up-to-date review on the incidence and pathogenesis of HF post-MI, current strategies to prevent and treat onset of HF post-MI, promising therapeutic strategies, and knowledge gaps in the field., Competing Interests: Declaration of competing interest Dr. Baron has received research support from Abiomed and Boston Scientific Corp; and has served as a consultant, on an advisory board, or as a paid speaker for Zoll Medical, Medtronic, Biotronik, Boston Scientific Corp, and Shockwave. Dr. Zieroth has received research grant support, served on advisory boards, or been a speaker for Abbott, Akcea Therapeutics, Inc., AstraZeneca, Amgen, Alnylam, Bayer, BMS, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novartis, NovoNordisk, Otsuka, Pfizer, Servier, and Vifor Pharma; and has served on a clinical trial steering committee or as a national lead for studies sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Merck, and Novartis. Dr. Estep has served as a consultant for Abbott, and as a medical advisor for Medtronic. Dr. Burkhoff has received institutional support from Abiomed, Alleviant, Axon Therapies, Edwards Lifesciences, and Fire1; and has received consulting fees from Aquapass, Axon Therapies, BackBeat Medical, Corvia, BioMind, Impulse Dynamics, and Therox/Zoll. Dr. Butler has served as a consultant for Abbott, Adrenomed AG, Amgen, American Regent, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3Pharmaceutical, ImpulseDynamics, Innolife, Janssen Pharmaceuticals, LivaNova, Medtronic, Merck, Novartis, NovoNordisk, Pfizer, Roche, and Vifor Pharma. Dr. Fudim is a consultant to Zoll. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: The PARAGLIDE-HF trial demonstrated reductions in natriuretic peptides with sacubitril/valsartan compared with valsartan in patients with heart failure (HF) with mildly reduced or preserved ejection fraction who had a recent worsening HF event, but was not adequately powered to examine clinical outcomes. PARAGON-HF included a subset of PARAGLIDE-HF-like patients who were recently hospitalized for HF. Participant-level data from PARAGLIDE-HF and PARAGON-HF were pooled to better estimate the efficacy and safety of sacubitril/valsartan in reducing cardiovascular and renal events in HF with mildly reduced or preserved ejection fraction., Methods and Results: Both PARAGLIDE-HF and PARAGON-HF were multicentre, double-blind, randomized, active-controlled trials of sacubitril/valsartan vs. valsartan in patients with HF with mildly reduced or preserved left ventricular ejection fraction (LVEF >40% in PARAGLIDE-HF and ≥45% in PARAGON-HF). In the pre-specified primary analysis, we pooled participants in PARAGLIDE-HF (all of whom were enrolled during or within 30 days of a worsening HF event) with a 'PARAGLIDE-like' subset of PARAGON-HF (those hospitalized for HF within 30 days). We also pooled the entire PARAGLIDE-HF and PARAGON-HF populations for a broader context. The primary endpoint for this analysis was the composite of total worsening HF events (including first and recurrent HF hospitalizations and urgent visits) and cardiovascular death. The secondary endpoint was the pre-specified renal composite endpoint for both studies (≥50% decline in estimated glomerular filtration rate from baseline, end-stage renal disease, or renal death). Compared with valsartan, sacubitril/valsartan significantly reduced total worsening HF events and cardiovascular death in both the primary pooled analysis of participants with recent worsening HF [n = 1088; rate ratio (RR) 0.78; 95% confidence interval (CI) 0.61-0.99; P = 0.042] and in the pooled analysis of all participants (n = 5262; RR 0.86; 95% CI: 0.75-0.98; P = 0.027). In the pooled analysis of all participants, first nominal statistical significance was reached by Day 9 after randomization, and treatment benefits were larger in those with LVEF ≤60% (RR 0.78; 95% CI 0.66-0.91) compared with those with LVEF >60% (RR 1.09; 95% CI 0.86-1.40; Pinteraction = 0.021). Sacubitril/valsartan was also associated with lower rates of the renal composite endpoint in the primary pooled analysis [hazard ratio (HR) 0.67; 95% CI 0.43-1.05; P = 0.080] and the pooled analysis of all participants (HR 0.60; 95% CI 0.44-0.83; P = 0.002)., Conclusion: In pooled analyses of PARAGLIDE-HF and PARAGON-HF, sacubitril/valsartan reduced cardiovascular and renal events among patients with HF with mildly reduced or preserved ejection fraction. These data provide support for use of sacubitril/valsartan in patients with HF with mildly reduced or preserved ejection fraction, particularly among those with an LVEF below normal, regardless of care setting., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Despite worsening heart failure (HF) being extremely common, expensive, and associated with substantial risk of death, there remain no dedicated clinical practice guidelines for the specific management of these patients. The lack of a management guideline is despite a rapidly evolving evidence-base, as a number of recent clinical trials have demonstrated multiple therapies to be safe and efficacious in this high-risk population. Herein, we propose a framework for treating worsening HF with reduced ejection fraction with the sense of urgency it deserves. This includes treating congestion; managing precipitants; and establishing a foundation of rapid-sequence, simultaneous, and/or in-hospital initiation of quadruple medical therapy for HF with reduced ejection fraction, with the top priority being at least low doses of all 4 medications. Moreover, to maximally reduce residual clinical risk, we further propose consideration of upfront simultaneous use of vericiguat (ie, quintuple medical therapy) and administration of intravenous iron for those who are iron deficient., Competing Interests: Funding Support and Author Disclosures Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, American Heart Association (#929502), National Heart, Lung, and Blood Institute, Amgen, AstraZeneca, Bristol Myers Squibb, Cytokinetics, Merck and Co, Inc, Novartis, Pfizer, and Sanofi; has served on advisory boards for Amgen, AstraZeneca, Boehringer Ingelheim and Eli Lilly, Bristol Myers Squibb, Cytokinetics, Roche Diagnostics, scPharmaceuticals, and Sanofi; has served as a consultant for Amgen, Bayer, Boehringer Ingelheim and Eli Lilly, Bristol Myers Squibb, Corteria Pharmaceuticals, CSL Vifor, Merck, Lexicon, PharmaIN, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from Boehringer Ingelheim, Cytokinetics, Lexicon, and Roche Diagnostics. Dr Bauersachs has received honoraria for lectures/consulting from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Cardior, Corvia, CVRx, Novartis, Pfizer, and Vifor; and has received research support for the department from Zoll, CVRx, and Abiomed. Dr Brugts has received research grants from Abbott, Vifor Pharma; and has received speaker fees from or has served on advisory boards for Abbott, Bayer, Boehringer, Novartis and Vifor Pharma. Dr Ezekowitz has received research grants and consulting fees from Bayer, Merck, Servier, Amgen, Sanofi, Novartis, Cytokinetics, American Regent, and Applied Therapeutics. Dr Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Bayer and Roche Diagnostics; has served as consultant or on the Advisory Board/Steering Committee/Executive Committee for Actelion, Alleviant Medical, Allysta Pharma, Amgen, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc, EchoNous Inc, Eli Lilly, Impulse Dynamics, Ionis Pharmaceutical, Janssen Research and Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, ProSciento Inc, Radcliffe Group Ltd, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and serves as cofounder and non-executive director of Us2.ai. Dr Lund has received grants from AstraZeneca, Vifor Pharma, Boston Scientific, Boehringer Ingelheim, and Novartis; has served as a consultant for Merck, Vifor Pharma, AstraZeneca, Bayer, Pharmacosmos, MedScape, Sanofi, Lexicon Pharmaceuticals Inc, Myokardia, Boehringer Ingelheim, and Servier; has received speaker honoraria from Abbott, MedScape, Radcliffe, AstraZeneca, Novartis, AnaCardio AB; and has stock ownership in AnaCardio AB. Dr Mentz has received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Medtronic, Merck, Novartis, Roche, Sanofi, and Vifor. Dr Pieske has been on the steering committee, advisory board, or has received speaker honoraria from Bayer Healthcare, MSD, BMS, Novartis, AstraZeneca, Edwards, Boehringer Ingelheim; and has minor shares in Imaging Clinical Trials Services (ICTS Germany). Dr Ponikowski has served as consultant or on the Advisory Board/Steering Committee/Executive Committee for Abbott Vascular, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Impulse Dynamics, Merck, Novartis, Radcliffe Group Ltd, Servier, and Vifor Pharma. Dr Voors has received consultancy fees and/or research grants paid to his employer from Anacardio, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Corteria, Cytokinetics, Merck, Novartis, Novo Nordisk, and Roche Diagnostics. Dr Zieroth has received research grant support, served on advisory boards or speaker engagements for Abbott, Akcea Therapeutics, Inc, AstraZeneca, Amgen, Alnylam, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Servier, and Vifor Pharma; and has served on a clinical trial steering committee or as a national lead for studies sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Merck, and Novartis. Dr Butler has served as a consultant for Abbott, Adrenomed AG, Amgen, American Regent, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen Pharmaceuticals, LivaNova, Medtronic, Merck, Novartis, Novo Nordisk, Pfizer, Roche, and Vifor Pharma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Acute cellular rejection (ACR), an alloimmune response involving CD4+ and CD8+ T cells, occurs in up to 20% of patients within the first year following heart transplantation. The balance between a conventional versus regulatory CD4+ T cell alloimmune response is believed to contribute to developing ACR. Therefore, tracking these cells may elucidate whether changes in these cell populations could signal ACR risk., Methods: We used a CD4+ T cell gene signature (TGS) panel that tracks CD4+ conventional T cells (Tconv) and regulatory T cells (Treg) on longitudinal samples from 94 adult heart transplant recipients. We evaluated combined diagnostic performance of the TGS panel with a previously developed biomarker panel for ACR diagnosis, HEARTBiT, while also investigating TGS' prognostic utility., Results: Compared with nonrejection samples, rejection samples showed decreased Treg- and increased Tconv-gene expression. The TGS panel was able to discriminate between ACR and nonrejection samples and, when combined with HEARTBiT, showed improved specificity compared with either model alone. Furthermore, the increased risk of ACR in the TGS model was associated with lower expression of Treg genes in patients who later developed ACR. Reduced Treg gene expression was positively associated with younger recipient age and higher intrapatient tacrolimus variability., Conclusions: We demonstrated that expression of genes associated with CD4+ Tconv and Treg could identify patients at risk of ACR. In our post hoc analysis, complementing HEARTBiT with TGS resulted in an improved classification of ACR. Our study suggests that HEARTBiT and TGS may serve as useful tools for further research and test development., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

A number of societies produce heart failure (HF) management guidelines, comprising official recommendations on the basis of recent research discoveries, but their applicability to specific situations encountered in daily practice might be difficult. In this clinical practice update we aim to provide responses to fundamental questions that face health care providers, like appropriate timing for the introduction and optimization of different classes of medication according to specific patient phenotypes, when second-line therapies and valvular interventions should be considered, and management of difficult clinical scenarios such as cardiorenal syndrome and frailty. A consensus-based methodology was used. Approaches to 5 different phenotypes are presented: (1) The wet HF phenotype is the easiest to manage, decongestion being performed alongside introduction of guideline-directed medical therapy (GDMT); (2) The de novo HF phenotype requires the introduction of the 4 pillars of GDMT, personalizing the order on the basis of the individuals' biological and physiological characteristics; (3) The worsening HF phenotype is a marker of poor prognosis, and therefore should motivate optimization of GDMT, start second-line therapies, and/or reevaluate goals of care/advanced HF therapies; (4) The cardiorenal phenotypes require correct volume assessment, because renal function usually improves with decongestion; and (5) The frail HF phenotype require special attention, careful drug titration, and consideration of cardiac rehabilitation programs. In conclusion, specific common HF phenotypes call for a personalized approach to improve adoption of the HF guidelines into clinical practice., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: U.S. guidelines recommend consideration of sacubitril/valsartan in chronic heart failure (HF) and mildly reduced or preserved ejection fraction (EF). Whether initiation is safe and effective in EF >40% after a worsening heart failure (WHF) event is unknown., Objectives: PARAGLIDE-HF (Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF) assessed sacubitril/valsartan vs valsartan in EF >40% following a recent WHF event., Methods: PARAGLIDE-HF is a double-blind, randomized controlled trial of sacubitril/valsartan vs valsartan in patients with EF >40% enrolled within 30 days of a WHF event. The primary endpoint was time-averaged proportional change in amino terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline through Weeks 4 and 8. A secondary hierarchical outcome (win ratio) consisted of: 1) cardiovascular death; 2) HF hospitalizations; 3) urgent HF visits; and 4) change in NT-proBNP., Results: In 466 patients (233 sacubitril/valsartan; 233 valsartan), time-averaged reduction in the NT-proBNP was greater with sacubitril/valsartan (ratio of change: 0.85; 95% CI: 0.73-0.999; P = 0.049). The hierarchical outcome favored sacubitril/valsartan but was not significant (unmatched win ratio: 1.19; 95% CI: 0.93-1.52; P = 0.16). Sacubitril/valsartan reduced worsening renal function (OR: 0.61; 95% CI: 0.40-0.93) but increased symptomatic hypotension (OR: 1.73; 95% CI: 1.09-2.76). There was evidence of a larger treatment effect in the subgroup with EF ≤60% for NT-proBNP change (0.78; 95% CI: 0.61-0.98) and the hierarchical outcome (win ratio: 1.46; 95% CI: 1.09-1.95)., Conclusions: Among patients with EF >40% stabilized after WHF, sacubitril/valsartan led to greater reduction in plasma NT-proBNP levels and was associated with clinical benefit compared with valsartan alone, despite more symptomatic hypotension. (Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF; NCT03988634)., Competing Interests: Funding Support and Author Disclosures PARAGLIDE-HF was funded by Novartis Pharmaceuticals Corporation. Dr Mentz has received research support and/or honoraria from Novartis, Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Medable, Merck, Novo Nordisk, Pharmacosmos, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. Drs Ward, Sarwat, and Williamson are employees of Novartis. Dr Hernandez has received research grants from American Regent, Amgen, AstraZeneca, Bayer, Bayer, Boehringer Ingelheim, Cytokinetics, Merck, Novartis, Somologic, and Verily; and has served as a consultant for Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Merck, Novartis, and Novo Nordisk. Dr Morrow is a member of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc, AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc, Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc, Janssen Research and Development, LLC, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Inc, Roche, Siemens Healthcare Diagnostics, Inc, Softcell Medical Limited, and Zora Biosciences; and has received consulting fees from Abbott Laboratories, ARCA Biopharma, Inflammatix, Merck and Co, Novartis, and Roche Diagnostics. Dr Sharma serves as an advisory board member and/or consultant to AstraZeneca, Alleviant, Bayer, Boehringer Ingelheim, Imbria, Novartis, Novo Nordisk, RIVUS, and ViCardia; and receives grant funding from Amgen and the American Heart Association. Dr Starling serves on the steering committee for the PARAGLIDE trial sponsored by Novartis. Dr Velazquez has received grants from Novartis, Amgen, Phillips, and the National Heart, Lung, and Blood Institute/National Institutes of Health. Dr Desai has received research grants (to BWH) from Abbott, Alnylam, AstraZeneca, Bayer, and Novartis; and has received personal consulting fees from Abbott, Alnylam, AstraZeneca, Avidity Biopharma, Axon Therapeutics, Bayer, Biofourmis, Cytokinetics, GlaxoSmithKline, Medpace, Merck, New Amsterdam, Novartis, Parexel, Regeneron, River2Renal, Roche, Verily, and Veristat. Dr Zieroth has received research grant support, served on advisory boards for, or has had speaker engagements with Abbott, Akcea AstraZeneca, Amgen, Alnylam, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, Servier and Vifor Pharma; and serves on a clinical trial committee or as a national lead for studies sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, and Pfizer. Dr Solomon has received research grants from Alnylam, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Cytokinetics, Eidos, GlaxoSmithKline, Ionis, Lilly, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, Actelion, Amgen, Bellerophon, Celladon, Gilead, Mesoblast, Neurotronik, and US2; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. Dr Braunwald has received grant support to his institution from Novartis for the conduct of the PIONEER-HF trial, for serving on the Executive Committee of the PARADISE-MI trial and the Steering Committee of the PARAGLIDE-HF trial, and for participation in an Advisory Board Meeting. Dr Lepage has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Many studies have demonstrated that physicians often err in estimating patient prognosis. No studies have directly compared physician to model predictive performance in heart failure (HF). We aimed to compare the accuracy of physician versus model predictions of 1-year mortality., Methods: This multicenter prospective cohort study on 11 HF clinics in 5 provinces in Canada included consecutive consented outpatients with HF with reduced left ventricular ejection fraction (<40%). By collecting clinical data, we calculated predicted 1-year mortality using the Seattle HF Model (SHFM), the Meta-Analysis Global Group in Chronic HF score, and the HF Meta-Score. HF cardiologists and family doctors, blinded to model predictions, estimated patient 1-year mortality. During 1-year follow-up, we recorded the composite end point of mortality, urgent ventricular assist device implant, or heart transplant. We compared physicians and model discrimination (C statistic), calibration (observed versus predicted event rate), and risk reclassification., Results: The study included 1643 patients with ambulatory HF with a mean age of 65 years, 24% female, and mean left ventricular ejection fraction of 28%. Over 1-year follow-up, 9% had an event. The SHFM had the best discrimination (SHFM C statistic 0.76; HF Meta-Score 0.73; Meta-Analysis Global Group in Chronic Heart Failure 0.70) and calibration. Physicians' discrimination differed little (0.75 for HF cardiologists and 0.73 for family doctors) but both physician groups substantially overestimated risk by >10% in both low- and high-risk patients (poor calibration). In risk reclassification analysis, among patients without events, the SHFM better classified 51% in comparison to HF cardiologists and 43% in comparison to family doctors. In patients with events, the SHFM erroneously assigned lower risk to 44% in comparison to HF cardiologists and 34% in comparison to family doctors., Conclusions: Family doctors and HF cardiologists showed adequate risk discrimination, with however substantial overestimation of absolute risk. Predictive models showed higher accuracy. Incorporating models in family and HF cardiology practices may improve patient care and resource use in HF with reduced left ventricular ejection fraction., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04009798., Competing Interests: Disclosures None.

Heart failure with preserved ejection fraction (HFpEF) represents a highly heterogeneous clinical syndrome affected in its development and progression by many comorbidities. The left ventricular diastolic dysfunction may be a manifestation of various combinations of cardiovascular, metabolic, pulmonary, renal, and geriatric conditions. Thus, in addition to treatment with sodium-glucose cotransporter 2 inhibitors in all patients, the most effective method of improving clinical outcomes may be therapy tailored to each patient's clinical profile. To better outline a phenotype-based approach for the treatment of HFpEF, in this joint position paper, the Heart Failure Association of the European Society of Cardiology, the European Heart Rhythm Association and the European Hypertension Society, have developed an algorithm to identify the most common HFpEF phenotypes and identify the evidence-based treatment strategy for each, while taking into account the complexities of multiple comorbidities and polypharmacy., (© 2023 European Society of Cardiology.)

Type 2 diabetes is one of the fastest-growing health emergencies of the twenty-first century, in part due to its association with cardiovascular and renal disease. Successful implementation of evidence-based guidelines for the management of patients with diabetes and pre-diabetes has been shown to improve patient outcomes by controlling risk factors for cardiovascular and renal disease. Recommendations include the early introduction of lifestyle adjustments, supported by pharmacological tools. Despite the availability of regularly updated, evidence-based guidelines, guideline implementation in clinical practice is low. As a result, people living with type 2 diabetes are not consistently receiving ideal clinical care. Improving guideline adherence has the potential to improve quality of life and longevity in patients with type 2 diabetes. This article introduces Guardians For Health, a global initiative that aims to improve guideline adherence by simplifying patient management and encouraging patient participation in the implementation of guidelines for type 2 diabetes. Guardians For Health is supported by a global community of implementers, with tools to support decision-making and quality assurance. Through achieving better guideline adherence, Guardians For Health hopes to achieve its vision to "stop early mortality by reducing cardiovascular and kidney complications in people with type 2 diabetes"., (© 2023. The Author(s).)