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Maria Rosa Costanzo,1 Shahrokh Javaheri,2,3 Piotr Ponikowski,4 Olaf Oldenburg,5 Ralph Augostini,3 Lee R Goldberg,6 Christoph Stellbrink,7 Henrik Fox,8 Alan R Schwartz,6 Sanjaya Gupta,9 Scott McKane,10 Timothy E Meyer,10 William T Abraham3 for the remedē®System Pivotal Trial Study Group1Advocate Heart Institute, Naperville, IL, USA; 2Bethesda North Hospital, Cincinnati, OH, USA; 3The Ohio State University, Columbus, OH, USA; 4Department of Heart Diseases, Medical University, Military Hospital, Wroclaw, Poland; 5Ludgerus-Kliniken Münster, Clemens Hospital, Münster, Germany; 6University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; 7Bielefeld Medical Center, Bielefeld, Germany; 8Clinic for General and Interventional Cardiology Angiology, Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany; 9University of Missouri-Kansas City School of Medicine, Saint Luke’s Mid-America Heart Institute, Kansas City, MO, USA; 10Respicardia, Inc., Minnetonka, MN, USACorrespondence: Maria Rosa CostanzoAdvocate Heart Institute, Naperville, IL, 60566, USAEmail mariarosa.costanzo@aah.orgBackground: The remedē System Pivotal Trial was a prospective, multi-center, randomized trial demonstrating transvenous phrenic nerve stimulation (TPNS) therapy is safe and effectively treats central sleep apnea (CSA) and improves sleep architecture and daytime sleepiness. Subsequently, the remedē System was approved by FDA in 2017. As a condition of approval, the Post Approval Study (PAS) collected clinical evidence regarding long-term safety and effectiveness in adults with moderate to severe CSA through five years post implant.Methods: Patients remaining in the Pivotal Trial at the time of FDA approval were invited to enroll in the PAS and consented to undergo sleep studies (scored by a central laboratory), complete the Epworth Sleepiness Scale (ESS) questionnaire to assess daytime sleepiness, and safety assessment. All subjects (treatment and former control group) receiving active therapy were pooled; data from both trials were combined for analysis.Results: Fifty-three of the original 151 Pivotal Trial patients consented to participate in the PAS and 52 completed the 5-year visit. Following TPNS therapy, the apnea-hypopnea index (AHI), central-apnea index (CAI), arousal index, oxygen desaturation index, and sleep architecture showed sustained improvements. Comparing 5 years to baseline, AHI and CAI decreased significantly (AHI baseline median 46 events/hour vs 17 at 5 years; CAI baseline median 23 events/hour vs 1 at 5 years), though residual hypopneas were present. In parallel, the arousal index, oxygen desaturation index and sleep architecture improved. The ESS improved by a statistically significant median reduction of 3 points at 5 years. Serious adverse events related to implant procedure, device or delivered therapy were reported by 14% of patients which include 16 (9%) patients who underwent a pulse generator reposition or lead revision (primarily in the first year). None of the events caused long-term harm. No unanticipated adverse device effects or related deaths occurred through 5 years.Conclusion: Long-term TPNS safely improves CSA, sleep architecture and daytime sleepiness through 5 years post implant.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01816776.Keywords: central sleep apnea, phrenic nerve stimulation

Background: Whether transcatheter mitral-valve repair improves outcomes in patients with heart failure and functional mitral regurgitation is uncertain., Methods: We conducted a randomized, controlled trial involving patients with heart failure and moderate to severe functional mitral regurgitation from 30 sites in nine countries. The patients were assigned in a 1:1 ratio to either transcatheter mitral-valve repair and guideline-recommended medical therapy (device group) or medical therapy alone (control group). The three primary end points were the rate of the composite of first or recurrent hospitalization for heart failure or cardiovascular death during 24 months; the rate of first or recurrent hospitalization for heart failure during 24 months; and the change from baseline to 12 months in the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS; scores range from 0 to 100, with higher scores indicating better health status)., Results: A total of 505 patients underwent randomization: 250 were assigned to the device group and 255 to the control group. At 24 months, the rate of first or recurrent hospitalization for heart failure or cardiovascular death was 37.0 events per 100 patient-years in the device group and 58.9 events per 100 patient-years in the control group (rate ratio, 0.64; 95% confidence interval [CI], 0.48 to 0.85; P = 0.002). The rate of first or recurrent hospitalization for heart failure was 26.9 events per 100 patient-years in the device group and 46.6 events per 100 patient-years in the control group (rate ratio, 0.59; 95% CI, 0.42 to 0.82; P = 0.002). The KCCQ-OS score increased by a mean (±SD) of 21.6±26.9 points in the device group and 8.0±24.5 points in the control group (mean difference, 10.9 points; 95% CI, 6.8 to 15.0; P<0.001). Device-specific safety events occurred in 4 patients (1.6%)., Conclusions: Among patients with heart failure with moderate to severe functional mitral regurgitation who received medical therapy, the addition of transcatheter mitral-valve repair led to a lower rate of first or recurrent hospitalization for heart failure or cardiovascular death and a lower rate of first or recurrent hospitalization for heart failure at 24 months and better health status at 12 months than medical therapy alone. (Funded by Abbott Laboratories; RESHAPE-HF2 ClinicalTrials.gov number, NCT02444338.)., (Copyright © 2024 Massachusetts Medical Society.)

Randomized clinical trials are the gold standard for establishing the efficacy and safety of cardiovascular therapies. However, current pivotal trials are expensive, lengthy, and insufficiently diverse. Emerging artificial intelligence (AI) technologies can potentially automate and streamline clinical trial operations. This review describes opportunities to integrate AI throughout a trial's life cycle, including designing the trial, identifying eligible patients, obtaining informed consent, ascertaining physiological and clinical event outcomes, interpreting imaging, and analyzing or disseminating the results. Nevertheless, AI poses risks, including generating inaccurate results, amplifying biases against underrepresented groups, and violating patient privacy. Medical journals and regulators are developing new frameworks to evaluate AI research tools and the data they generate. Given the high-stakes role of randomized trials in medical decision making, AI must be integrated carefully and transparently to protect the validity of trial results., Competing Interests: Funding Support and Author Disclosures Dr Cunningham has received support from the KL2/Harvard Catalyst Medical Research Investigator Training program and the American Heart Association (23CDA1052151); and has received consulting fees from Roche Diagnosis, Edgewise Therapeutics, KCK, and Occlutech. Dr Abraham has served as a consultant to Boehringer Ingelheim, CVRx, Impulse Dynamics, Sensible Medical, Vectorious, V-Wave, and Zoll Respicardia. Dr Bhatt has received research grant support to his institution from the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) and National Institute on Aging, the American College of Cardiology Foundation, and the Centers for Disease Control and Prevention (CDC); and has received consulting fees from the Kinetix Group, Merck, Sanofi Pasteur, and Novo Nordisk. Dr Dunn has served as a scientific advisor to Veri. Dr Felker has received research grants from NIH, Bayer, Bristol Myers Squibb, Novartis, Daxor, Merck, Cytokinetics, and CSL-Behring; has acted as a consultant to Novartis, Bristol Myers Squibb, Cytokinetics, Innolife, Boehringer Ingelheim, Abbott, Sanofi, Regeneron, Myovant, Sequana, Windtree Therapeutics, and Whiteswell; and has served on clinical endpoint committees or data safety monitoring boards for Merck, Medtronic, EBR Systems, Rocket Pharma, V-Wave, and LivaNova. Dr Jain has received consulting fees from Bristol Myers Squibb, ARTIS Ventures, and Broadview Ventures outside of the submitted work. Dr Lindsell has received grants and contracts from the NIH, the U.S. Department of Defense, CDC, Biomeme, Novartis, bioMérieux, AstraZeneca, AbbVie, Entegrion, and Endpoint Health, all outside of the submitted work; has obtained patents for risk stratification in sepsis and septic shock issued to Cincinnati Children’s Hospital Medical Center; has served on data safety monitoring boards unrelated to the current work; has held stock options in Bioscape Digital unrelated to the current work; and has served as Editor-in-Chief of the Journal of Clinical and Translational Science. Mr Mace is an employee of Acorai AB; and has held stock interest in Abbott Laboratories. Dr Martyn has served as an advisor to or has received consulting fees from Fire1, Cleveland Clinic/American Well Joint Venture, Boehringer Ingelheim/Eli Lilly, NIRSense, Novo Nordisk, AstraZeneca, and Apricity Robotics; and has received grant support from Ionis Therapeutics, AstraZeneca, and the Heart Failure Society of America. Dr Shah is an employee of Meta, which had no role in this work or providing financial support. Dr Tison has received research grants from MyoKardia, a wholly owned subsidiary of Bristol Myers Squibb, and Janssen Pharmaceuticals; and is an advisor to Viz.ai and Prolaio. Dr Fakhouri is an employee of the Office of Medical Policy, Center for Drug Evaluation and Research, U.S. Food and Drug Administration; the views expressed in this article are those of the authors and do not necessarily represent the views or policies of the U.S. Food and Drug Administration. Dr Krumholz has received options from Element Science and Identifeye; has received payments from F-Prime for advisory roles; has co-founded and held equity in Hugo Health, Refactor Health, and ENSIGHT-AI; and has been associated with research contracts through Yale University from Janssen, Kenvue, and Pfizer. Dr O’Connor has received consulting fees from Merck, Abiomed, and Zealcare. Dr Solomon has received research grants from Alexion, Alnylam, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Boston Scientific, Cytokinetics, Edgewise, Eidos, Gossamer, GSK, Ionis, Lilly, MyoKardia, NIH NHLBI, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, MyoKardia, Novartis, Roche, Theracos, Quantum Genomics, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, AnaCardio, Akros, and Valo. Drs Psotka and Fiuzat 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.)

Background: Data on whether cardiac resynchronization therapy (CRT) results in better clinical and echocardiographic outcomes in patients with nonischemic cardiomyopathy (NICM) vs ischemic cardiomyopathy (ICM) are conflicting., Objectives: The authors conducted this meta-analysis of 7 clinical trials of CRT to determine the association between etiology of cardiomyopathy and clinical and echocardiographic outcomes., Methods: The authors analyzed patient-level data using Bayesian Hierarchical Weibull survival regression modeling to determine the association between etiology of cardiomyopathy and time to all-cause death or heart failure hospitalization (HFH). Linear regression was used to assess the association between etiology of cardiomyopathy and echocardiographic measurements., Results: Of 6,252 patients included, 4,717 (75%) were men, median age was 66 years (IQR: 58-73 years), 3,704 (59%) had ICM, and 3,778 (60%) received CRT. CRT increased the time to HFH or all-cause death (HR: 0.67; 95% credible interval [CrI]: 0.56-0.82; P < 0.001) with no difference by etiology of cardiomyopathy (HR ratio: 1.06 [95% CrI: 0.87-1.29]; P = 0.57). Likewise, CRT increased the time to all-cause death (HR: 0.71 [95% CrI: 0.55-0.93]; P = 0.019) with no difference by etiology of cardiomyopathy (HR ratio: 1.06 [95% CrI: 0.80-1.43]; P = 0.70). Echocardiographic data that were available for 2,430 (39%) patients showed that CRT improvements in left ventricular ejection fraction, left ventricular end-diastolic diameter, and left ventricular end-systolic diameter were larger for patients with NICM., Conclusions: Although CRT led to greater increases in left ventricular ejection fraction and reductions in ventricular dimensions for patients with NICM compared with those with ICM, CRT significantly increased the time to HFH or all-cause death independently of the etiology of cardiomyopathy. Further studies on improving patient selection for CRT are needed., Competing Interests: Funding Support and Author Disclosures Primary funding was provided by the National Heart, Lung, and Blood Institute (NHLBI) (1R01HL131754). Dr Cleland has received grants and personal fees from Pharmacosmos; personal honoraria from Abbott, AstraZeneca, Idorsia, Myokardia, NI Medical, Novartis, Servier, and Torrent Pharmaceuticals; grants and personal honoraria from Amgen/Cytokinetics, Bayer, Bristol Myers Squibb, Johnson & Johnson, Medtronic, Vifor, and Viscardia; and personal honoraria and nonfinancial support from Boehringer-Ingelheim outside of the submitted work. Dr Curtis serves on medical advisory boards for Janssen Pharmaceuticals, Medtronic, Abbott, Milestone Pharmaceuticals, and Eagle Pharmaceuticals; and she has received honoraria for speaking from Abbott and Medtronic. Dr Friedman has received research support from the American Heart Association, Boston Scientific, Biosense Webster, Merit Medical, Medtronic, National Institutes of Health, and Abbott; and consulting fees from Abbott, AtriCure, Microport, NI Medical, and Sanofi. Dr Gold serves on a medical advisory board for CVRx and EBR; has received research support to his institution from Boston Scientific, Abbott, and Medtronic; and is a consultant to Boston Scientific, Abbott, and Medtronic. Dr Linde has received research support to her institution from the Swedish Heart-Lung Foundation, Swedish Academy of Science, Roche Diagnostics, AstraZeneca, and Stockholm County Council; and speaker honoraria from Medtronic, Impulse Dynamics, Bayer, Boeringer Ingelheim, Novartis, Vifor Pharma, and Microport. Dr Al-Khatib has received research funding from Medtronic and Boston Scientific through grants to her institution. 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.)

Over the past decade, the field of heart failure (HF) has witnessed remarkable progress in drug development, resulting in the approval of numerous groundbreaking drugs by the U.S. Food and Drug Administration. To address some of these challenges, the U.S. Food and Drug Administration has issued guidance documents that have been critical in contemporary HF drug development; however, there are still many challenges in need of investigation. This paper leverages efforts of the Heart Failure Collaboratory and the scientific community to discuss the critical need for innovative trial designs, important concepts in clinical trials in the modern era, and the utilization of big data to accelerate HF drug development. At this inflection point in HF drug development, it is imperative that, as a global scientific community, we foster increased collaboration among researchers, clinicians, patients, and regulatory bodies. Only through such unified efforts can we navigate the complexities of HF, accelerate the development process, and ultimately deliver effective therapies that transform patient outcomes., Competing Interests: Funding Support and Author Disclosures Dr Januzzi has a board position with Imbria Pharma; has received grant support from Abbott, Applied Therapeutics, AstraZeneca, BMS, and Novartis Pharmaceuticals; has received consulting income from Abbott Diagnostics, Beckman-Coulter, Jana Care, Janssen, Novartis, Prevencio, Quidel, and Roche Diagnostics; and has served on clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Amgen, CVRx, Medtronic, Pfizer, and Roche Diagnostics. Dr Lindenfeld has received consulting fees from Abbott, Adona, Axon, Alleviant, AstraZeneca, Boston Scienrific, CVRx, Cordio, Edwards Lifesciences, Medtronic, Merck, Orchestra Biomed, VWave, Whiteswell, and Vascular Dynamics; and has received grant funding from AstraZeneca and Volumetrix. Dr Solomon has received research grants from Alnylam, AstraZeneca, Bellerophon, Bayer, BMS, Cytokinetics, Eidos, Gossamer, GlaxoSmithKline, Ionis, Lilly, MyoKardia, National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI), Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, 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 Bristow has been a consultant for ARCA Biopharma. Dr Abraham has received research grant support from the NHLBI (NIH 1 UG3/UH3 HL140144-01, 08/01/18-07/31/22, “Impact of Low Flow Nocturnal Oxygen Therapy on Hospital Readmission/Mortality in Patients with Heart Failure and Central Sleep Apnea [LOFT-HF]”); has received consulting income from Abbott Vascular, Boehringer Ingelheim, and Zoll Respicardia; has received speaker honoraria from Impulse Dynamics; and has received salary support from V-Wave Medical. Dr O'Connor has done consulting for Abiomed and Merck. 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: 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.)

Aims: Central sleep apnoea (CSA) is present in 20-40% of heart failure (HF) patients and is associated with poor clinical outcomes and health status. Transvenous phrenic nerve stimulation (TPNS) is an available treatment for CSA in HF patients. The impact on HF outcomes is incompletely understood. The win ratio (WR) allows inclusion of multiple endpoint components, considers the relative severity of each component, and permits assessment of recurrent events in evaluation of clinical benefit., Methods and Results: A WR hierarchy was pre-defined for analysis of the HF subgroup of the remedē® System Pivotal Trial. The analysis used three hierarchical components to compare all treated to all control subjects: longest survival, lowest HF hospitalization rate, and ≥2-category difference in Patient Global Assessment at 6 months. Sensitivity analyses were performed substituting Epworth Sleepiness Scale and 4% oxygen desaturation index for the third component, and a 4-component WR hierarchy was also evaluated. Ninety-one HF subjects, 43 receiving TPNS and 48 in the control group, provided 2064 pairwise comparisons. More patients treated with TPNS experienced clinical benefit compared with control (WR 4.92, 95% confidence interval 2.27-10.63, P < 0.0001). There were 1111 (53.83%) winning pairwise comparisons for the treatment group and 226 (10.95%) for the control group. Similarly, large WRs were observed for all additional WR hierarchies., Conclusions: This WR analysis of the remedē® System Pivotal Trial suggests that TPNS may be superior to untreated CSA in HF patients with CSA using a hierarchical clinical benefit endpoint composed of mortality, HF hospitalization, and health status., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Heart failure and chronic kidney disease are common and clinically important conditions that regularly coexist. Electrophysiologic changes of advanced heart failure often result in abnormal conduction, causing dyssynchronous contraction, and development of ventricular arrhythmias, which can lead to sudden cardiac arrest. In the last 2 decades, implantable cardioverter-defibrillator and cardiac resynchronization therapy devices have been developed to address these complications. However, when the coexisting chronic kidney disease is advanced, the associated pathophysiologic cardiovascular changes can alter the efficacy and safety of those interventions and complicate the management. This review explores the impact of comorbid advanced heart failure and advanced chronic kidney disease on the efficacy and safety of implantable cardioverter-defibrillator and cardiac resynchronization therapy, the currently available evidence, and potential future directions., Competing Interests: Funding Support and Author Disclosures Dr Cleland has received research grants from Bristol Myers Squibb, CSL-Vifor, and Pharmacosmos; and has received honoraria for advisory boards and speaking from Biopeutics, Boehringer Ingelheim, Bristol Myers Squibb, CSL-Vifor, and Pharmacosmos. Dr Abraham has received personal fees from Medtronic and Abbott. Dr Lip is a consultant and speaker for Bristol Myers Squibb/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, and Anthos, no fees are received personally; is a National Institute for Health and Care Research (NIHR) Senior Investigator and coprincipal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 899871. Dr Hatamizadeh has served as advisory board member for Horizon Therapeutics; and receives research support from Sarfez Pharmaceutical Company. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Aims: Interatrial shunts are under evaluation as a treatment for heart failure (HF); however, their in vivo flow performance has not been quantitatively studied. We aimed to investigate the fluid dynamics properties of the 0.51 cm orifice diameter Ventura shunt and assess its lumen integrity with serial transesophageal echocardiography (TEE)., Methods and Results: Computational fluid dynamics (CFD) and bench flow tests were used to establish the flow-pressure relationship of the shunt. Open-label patients from the RELIEVE-HF trial underwent TEE at shunt implant and at 6 and 12 month follow-up. Shunt effective diameter (D eff ) was derived from the vena contracta, and flow was determined by the continuity equation. CFD and bench studies independently validated that the shunt's discharge coefficient was 0.88 to 0.89. The device was successfully implanted in all 97 enrolled patients; mean age was 70 ± 11 years, 97% were NYHA class III, and 51% had LVEF ≤40%. Patency was confirmed in all instances, except for one stenotic shunt at 6 months. D eff remained unchanged from baseline at 12 months (0.47 ± 0.01 cm, P = 0.376), as did the trans-shunt mean pressure gradient (5.1 ± 3.9 mmHg, P = 0.316) and flow (1137 ± 463 mL/min, P = 0.384). TEE measured flow versus pressure closely correlated (R 2  ≥ 0.98) with a fluid dynamics model. At 12 months, the pulmonary/systemic flow Qp/Qs ratio was 1.22 ± 0.12., Conclusions: When implanted in patients with advanced HF, this small interatrial shunt demonstrated predictable and durable patency and performance., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Cardiac implantable electrical devices such as cardiac resynchronization therapy with defibrillator (CRT-Ds) or cardiac contractility modulation (CCMs) are therapy options for patients with symptomatic heart failure (HF) and reduced left ventricular ejection fraction (LVEF) despite optimal medical treatment. As yet, a comparison between both devices has not been performed., Methods and Results: The Mannheim Cardiac Resynchronization Therapy Registry (MARACANA) and the Mannheim Cardiac Contractility Modulation Observational Study (MAINTAINED) included all patients who received CRTs or CCMs in our medical centre between 2012 and 2021. For the present analysis, we retrospectively compared patients provided with either CRT-Ds (n = 220) or CCMs with additional defibrillators (n = 105) regarding New York Heart Association classification (NYHA), LVEF, tricuspid annular plane systolic excursion (TAPSE), QRS-width and other HF modification aspects after 12 months. Before implantation, CCM patients presented with lower LVEF (23.6 ± 6.2 vs. 26.3 ± 6.5%) and worse NYHA (3.03 ± 0.47 vs. 2.81 ± 0.48, both P < 0.05), compared with CRT-D patients. Follow-up improvements in NYHA (2.43 ± 0.67 vs. 2.28 ± 0.72), LVEF (30.5 ± 10.7 vs. 35.2 ± 10.5%) and TAPSE (17.2 ± 5.2 vs. 17.1 ± 4.8 to 18.9 ± 3.4 vs. 17.3 ± 3.6 mm, each P < 0.05) were comparable. The intrinsic QRS-width was stable with CCM (109.1 ± 18 vs. 111.7 ± 19.7 ms, P > 0.05), while the paced QRS-width with CRT-D after 12 months was lower than intrinsic values at baseline (157.5 ± 16.5 vs. 139.2 ± 16 ms, P < 0.05). HF hospitalizations occurred more often for CCM than CRT-D patients (45.7 vs. 16.8%/patient years, odds ratio 4.2, P < 0.001)., Conclusions: Chronic heart failure patients could experience comparable 12-month improvements in functional status and ventricular reverse remodelling, with appropriately implanted CCMs and CRT-Ds. Differences in HF hospitalization rates may be due to the more advanced HF of CCM patients at implantation., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: An interatrial shunt may provide an autoregulatory mechanism to decrease left atrial pressure and improve heart failure (HF) symptoms and prognosis., Methods: Patients with symptomatic HF with any left ventricular ejection fraction (LVEF) were randomized 1:1 to transcatheter shunt implantation versus a placebo procedure, stratified by reduced (≤40%) versus preserved (>40%) LVEF. The primary safety outcome was a composite of device-related or procedure-related major adverse cardiovascular or neurological events at 30 days compared with a prespecified performance goal of 11%. The primary effectiveness outcome was the hierarchical composite ranking of all-cause death, cardiac transplantation or left ventricular assist device implantation, HF hospitalization, outpatient worsening HF events, and change in quality of life from baseline measured by the Kansas City Cardiomyopathy Questionnaire overall summary score through maximum 2-year follow-up, assessed when the last enrolled patient reached 1-year follow-up, expressed as the win ratio. Prespecified hypothesis-generating analyses were performed on patients with reduced and preserved LVEF., Results: Between October 24, 2018, and October 19, 2022, 508 patients were randomized at 94 sites in 11 countries to interatrial shunt treatment (n=250) or a placebo procedure (n=258). Median (25th and 75th percentiles) age was 73.0 years (66.0, 79.0), and 189 patients (37.2%) were women. Median LVEF was reduced (≤40%) in 206 patients (40.6%) and preserved (>40%) in 302 patients (59.4%). No primary safety events occurred after shunt implantation (upper 97.5% confidence limit, 1.5%; P <0.0001). There was no difference in the 2-year primary effectiveness outcome between the shunt and placebo procedure groups (win ratio, 0.86 [95% CI, 0.61-1.22]; P =0.20). However, patients with reduced LVEF had fewer adverse cardiovascular events with shunt treatment versus placebo (annualized rate 49.0% versus 88.6%; relative risk, 0.55 [95% CI, 0.42-0.73]; P <0.0001), whereas patients with preserved LVEF had more cardiovascular events with shunt treatment (annualized rate 60.2% versus 35.9%; relative risk, 1.68 [95% CI, 1.29-2.19]; P =0.0001; P interaction <0.0001). There were no between-group differences in change in Kansas City Cardiomyopathy Questionnaire overall summary score during follow-up in all patients or in those with reduced or preserved LVEF., Conclusions: Transcatheter interatrial shunt implantation was safe but did not improve outcomes in patients with HF. However, the results from a prespecified exploratory analysis in stratified randomized groups suggest that shunt implantation is beneficial in patients with reduced LVEF and harmful in patients with preserved LVEF., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03499236.

Heart failure (HF) and moderate-to-severe mitral regurgitation (MR) with residual elevations in left atrial pressure (LAP) after MitraClip may remain symptomatic and experience subsequent HF readmissions. The V-Wave interatrial shunt system is a permanent interatrial septal implant that shunts blood from the left-to-right atrium and serves to continuously unload the left atrium. Although the V-Wave shunt has previously been studied in patients with HF, the safety and feasibility of its deployment at the time of the MitraClip procedure is unknown. The V-Wave Shunt MitraClip Study (NCT04729933) is an early feasibility study that aims to demonstrate the safety and efficacy of implantation of the V-Wave shunt device at the time of MitraClip procedure. Patients with moderate-to-severe secondary MR with left ventricular ejection fraction 20% to 50% and New York Heart Association functional class III/IV symptoms despite optimal medical therapy, residual mean LAP ≥20 mm Hg after MitraClip, and mean LAP-right atrial pressure difference ≥5 mm Hg are included. The primary safety end point is a composite outcome of all-cause death, stroke, myocardial infarction device embolization, cardiac tamponade, or device-related re-intervention or surgery at 30 days. Patients will be followed up to 5 years. Enrollment is ongoing, with 30-day results expected by the end of 2024. The V-Wave Shunt Mitraclip Study aims to demonstrate the safety and efficacy of the implantation of the V-Wave interatrial shunt device at the time of index MitraClip placement which may serve as an adjunctive method by which continuous left atrial unloading may be achieved., Competing Interests: Declaration of competing interest Dr. Abraham is the Chief Medical Officer of V-Wave Ltd. The remaining authors have no competing interests to declare., (Copyright © 2024. Published by Elsevier Inc.)

Background: Functional mitral regurgitation induces adverse effects on the left ventricle and the left atrium. Left atrial (LA) dilatation and reduced LA strain are associated with poor outcomes in heart failure (HF). Transcatheter edge-to-edge repair (TEER) of the mitral valve reduces heart failure hospitalization (HFH) and all-cause death in selected HF patients., Objectives: The aim of this study was to evaluate the impact of LA strain improvement 6 months after TEER on the outcomes of patients enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial., Methods: The difference in LA strain between baseline and the 6-month follow-up was calculated. Patients with at least a 15% improvement in LA strain were labeled as "LA strain improvers." All-cause death and HFH were assessed between the 6- and 24-month follow-up., Results: Among 347 patients (mean age 71 ± 12 years, 63% male), 106 (30.5%) showed improvement of LA strain at the 6-month follow-up (64 [60.4%] from the TEER + guideline-directed medical therapy [GDMT] group and 42 [39.6%] from the GDMT alone group). An improvement in LA strain was significantly associated with a reduction in the composite of death or HFH between the 6-month and 24-month follow-up, with a similar risk reduction in both treatment arms (P interaction  = 0.27). In multivariable analyses, LA strain improvement remained independently associated with a lower risk of the primary composite endpoint both as a continuous variable (adjusted HR: 0.94 [95% CI: 0.89-1.00]; P = 0.03) and as a dichotomous variable (adjusted HR: 0.49 [95% CI: 0.27-0.89]; P = 0.02). The best outcomes were observed in patients treated with TEER in whom LA strain improved., Conclusions: In symptomatic HF patients with severe mitral regurgitation, improved LA strain at the 6-month follow-up is associated with subsequently lower rates of the composite endpoint of all-cause mortality or HFH, both after TEER and GDMT alone. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079)., Competing Interests: Funding Support and Author Disclosures The COAPT trial was sponsored by Abbott. Dr Delgado received speaker fees from Abbott Vascular, Edwards Lifesciences, Merck Sharp and Dohme, and GE Healthcare. Dr Stassen has received funding from the European Society of Cardiology (European Society of Cardiology Training Grant App000064741). Dr Weissman is associate director of an academic echocardiography core laboratory (MedStar Health Research Institute) with institutional contracts with Abbott, Neovasc, Ancora, Mitralign, Medtronic, Boston Scientific, Edwards Lifesciences, Biotronik, and Livanova. Dr Grayburn has received grant support from Abbott Vascular, Medtronic, Boston Scientific, Cardiovalve, Edwards Lifesciences, W. L. Gore, Medtronic, and NeoChord; and has received consulting fees from Abbott Vascular, Edwards Lifesciences, W. L. Gore, and 4C Medical. Dr Kar has received consulting fees and is an Advisory Board member at Boston Scientific; has received consulting fees and stock equity from Valcare; and has received consulting fees from W.L. Gore and Medtronic. Dr Lim has received research grant support from Abbott, Boston Scientific, Edwards, and Medtronic; has received consultant fees from LagonaTech, Valgen, and Venus; and is an Advisory Board member for Ancora and Philips. Dr Lindenfeld has received research grant support from AstraZeneca; and has received consulting fees from Abbott Vascular, CVRx, Edwards Lifesciences, RESMED, Relypsa, Boehringer Ingelheim, and V-Wave. Dr Abraham has received research grant support from the National Heart, Lung, and Blood Institute (National Institutes of Health 1 UG3/UH3 HL140144-01, 08/01/18-07/31/22, “Impact of Low Flow Nocturnal Oxygen Therapy on Hospital Readmission/Mortality in Patients with Heart Failure and Central Sleep Apnea [LOFT-HF]”); has received consulting income from Abbott Vascular, Boehringer-Ingelheim, and Zoll Respicardia; has received speaker honoraria from Impulse Dynamics; and has received salary support from V-Wave Medical. Dr Mack has served as coprimary investigator for the PARTNER Trial for Edwards Lifesciences and COAPT trial for Abbott; and has served as study chair for the APOLLO trial for Medtronic. Dr Asch is the Director of the Core Laboratories at MedStar Health Research Institute, which has institutional contracts (no personal compensation) with Abbott, Neovasc, Ancora, Mitralign, Medtronic, Boston Scientific, Edwards Lifesciences, Biotronik, and Livanova. Dr Stone has received speaker honoraria from Medtronic, Pulnovo, and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, and Millennia Biopharma; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Stone’s daughter is an employee at Medtronic; and Dr Stone’s employer, Mount Sinai Hospital, has received research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. Dr Bax has received speaker fees from Abbott Vascular. 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.)

Background: For patients with functional mitral regurgitation (FMR) and symptomatic heart failure (HF), randomized trials of mitral transcatheter edge-to-edge repair (M-TEER) have produced conflicting results., Objectives: This study sought to assess the impact of M-TEER on hospitalization rates, and explore the effects of M-TEER on patients who did or did not have a history of recent HF hospitalizations before undergoing M-TEER., Methods: RESHAPE-HF2 (Randomized Investigation of the MitraClip Device in Heart Failure: 2nd Trial in Patients with Clinically Significant Functional Mitral Regurgitation) included patients with symptomatic HF and moderate to severe FMR (mean effective regurgitant orifice area 0.25 cm 2 ; 14% >0.40 cm 2 , 23% <0.20 cm 2 ) and showed that M-TEER reduced recurrent HF hospitalizations with and without the addition of cardiovascular (CV) death and improved quality of life. We now report the results of prespecified analyses on hospitalization rates and for the subgroup of patients (n = 333) with a HF hospitalization in the 12 months before randomization., Results: At 24 months, the time to first event of CV death or HF hospitalization (HR: 0.65; 95% CI: 0.49-0.85; P = 0.002), the rate of recurrent CV hospitalizations (rate ratio [RR]: 0.75; 95% CI: 0.57-0.99; P = 0.046), the composite rate of recurrent CV hospitalizations and all-cause mortality (RR: 0.74; 95% CI: 0.57-0.95; P = 0.017), and of recurrent CV death and CV hospitalizations (RR: 0.76; 95% CI: 0.58-0.99; P = 0.040), were all lower in the M-TEER group. The RR of recurrent hospitalizations for any cause was 0.82 (95% CI: 0.63-1.07; P = 0.15) for patients in the M-TEER group vs control group patients. Patients randomized to M-TEER lost fewer days due to death or HF hospitalization (13.9% [95% CI: 13.0%-14.8%] vs 17.4% [95% CI: 16.4%-18.4%] of follow-up time; P < 0.0001, and 1,067 vs 1,776 total days lost; P < 0.0001). Patients randomized to M-TEER also had better NYHA functional class at 30 days and at 6, 12, and 24 months of follow-up (P < 0.0001). A history of HF hospitalizations before randomization was associated with worse outcomes and greater benefit with M-TEER on the rate of the composite of recurrent HF hospitalizations and CV death (P interaction  = 0.03) and of recurrent HF hospitalizations within 24 months (P interaction  = 0.06)., Conclusions: These results indicate that a broader application of M-TEER in addition to optimal guideline-directed medical therapy should be considered among patients with symptomatic HF and moderate to severe FMR, particularly in those with a history of a recent hospitalization for HF., Competing Interests: Funding Support and Author Disclosures Prof Ponikowsaki has received a grant from Vifor Pharma; has received consulting fees and/or honoraria from Boehringer Ingelheim, AstraZeneca, Vifor Pharma, Servier, Novartis, Berlin Chemie, Bayer, Abbott Vascular, Novo Nordisk, Pharmacosmos, Moderna, Pfizer, and Abbott Vascular; and has received fees for trial committee work from Boehringer Ingelheim, Vifor Pharma, Novo Nordisk, Pharmacosmos, and Moderna. Dr Friede has received payments to his institution from Abbott; has received grants from Deutsche Forschungsgemeinschaft (DFG), Federal Joint Committee (G-BA), and European Commission; has received consulting fees from Actimed, Bayer, BMS, CSL Behring, Daiichi-Sankyo, Galapagos, Immunic, KyowaKirin, LivaNova, Minoryx, Novartis, RECARDIO, Relaxera, Roche, Servier, Viatris, and Vifor; has received payments from Fresenius Kabi and PINK gegen Brustkrebs; is a trial data monitoring committee member for Aslan, Bayer, Biosense Webster, Enanta, Galapagos, IQVIA, Novartis, PPD, Recordati, Roche, and VICO Therapeutics; and is a trial steering committee member for SCLBehring. Dr von Bardeleben has received an EchoCoreLab IIT grant from Clinical Trial Unit of UMG Göttingen; has received consulting fees from Abbott Vascular, Jenscare, Edwards Lifesciences, and Medtronic; has received honoraria from Abbott Vascular, Jenavalve, Jenscare, Edwards Lifesciences, Medtronic, Philips, Siemens; and is a trial committee member for Medtronic and Heart Valve Society (unpaid), and EU SHD Coalition (unpaid). Dr Butler has received consulting fees from Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, Cardiorem, CSL Bearing, CVRx, Cytokinetics, Daxor, Edwards Lifesciences, 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, Pfize, Prolaio, Regeneron, Renibus, Roche, Salamandra, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll; and has received honoraria from Novartis, Boehringer Ingelheim-Lilly, AstraZeneca, Impulse Dynamics, and Vifor. Dr Khan has participated in a data safety monitoring board or advisory board for Bayer. Dr Ferrari has received honoraria and support for attending meetings from Servier, Merck Serono, Bayer, Lupin, and Sunpharma. Dr Abraham has received payments from Abbott; has received grants from National Institutes of Health 1 UG3 / UH3 HL140144-01; has received consulting fees from Zoll Respicardia; has received honoraria from Impulse Dynamics, Edwards Lifesciences, and Abbott; and is an advisory board member for Sensible Medical, WhiteSwell, AquaPass, Cordio Medical, and Boehringer Ingelheim. Dr Auricchio has received consulting fees and honoraria from Boston Scientific, Medtronic, Microport CRM, Philips, Xspline, and Abbott. Dr Bayes-Genis has lectured and/or participated in advisory boards for Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Novo Nordisk, Roche Diagnostics, and Vifor. Dr Cleland has received grants from Bristol Myers Squibb, CSL-Vifor, British Heart Foundation, and Pharmacosmos; has received consulting fees from Pharmacosmos, CSL-Vifor, and Biopeutics; and has received honoraria from Pharmacosmos. Dr Filippatos has received honoraria from Bayer, Boehringer Ingelheim, Servier, and Novartis; has served on the trial committee boards for Bayer, Medtronic, Boehringer Ingelheim, Vifor, Amgen, Servier, Impulse Dynamics, Cardior, and Novo Nordisk; and has served on the boards of the Heart Failure Association and JACC Heart Failure. Dr Gustafsson has received consulting fees and/or honoraria from Abbott, Bayer, Pfizer, and AstraZeneca; has participated on the trial committee board of AdJuCor; and has served on the board of the Heart Failure Association. Dr Haverkamp has received consulting fees and/or honoraria from Bayer and AstraZeneca. Dr Kelm has received grants or contracts from Microvision Medical Holding B.V., Edwards Lifesciences, Mars Scientific Advisory Council, Abiomed Europe GmbH, B. Braun Melsungen AG, DFG SFB 1116, EU Horizon 2020, and Daiichi-Sankyo Deutschland GmbH; and has received payment or honoraria from Bayer Vital GmbH, Abiomed Europe GmbH, AstraZeneca, Amarin GmbH, and CTI congress GmbH. Dr Landmesser has received grants from Abbott and Novartis; and has received consulting fees and honoraria from Abbott. Dr Maggioni has participated on trial committee boards for Bayer, AstraZeneca, Novartis, and Sanofi. Dr Metra has received consulting fees from Abbott Structural Heart, Boehringer Ingelheim, AstraZeneca, Roche Diagnostics, Edwards Lifesciences, Novo Nordisk, and Bayer. Dr Petrie has received grants from Boehringer Ingelheim, Roche Diagnostics, SQ Innovations, AstraZeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, and Pharmacosmos; has received consulting fees and/or honoraria from Akero, Applied Therapeutics, Amgen, AnaCardio, Biosensors, Boehringer Ingelheim, Corteria, FIRE-1, Biosensors, REPRIEVE, Corvia, Novartis, AstraZeneca, Novo Nordisk, AbbVie, Bayer, Horizon Therapeutics, Takeda, Cardiorentis, Pharmacosmos, Roche Pharma, Siemens, Eli Lilly, Vifor, New Amsterdam, Moderna, Teikoku, LIB Therapeutics, and 3R Lifesciences; and has participated on a data safety monitoring board or advisory board for AstraZeneca, Moderna, and Teikoku. Dr Rassaf has received consulting fees and/or honoraria from BMS, AstraZeneca, Pfizer, Novartis, Bayer, Daiichi-Sankyo, and CVRxInc; and has pending patent applications regarding amelioration and treatment of infarct damage (W02023079141A2), blood pressure lowering composition (EP3646861A1), and Bnip3 peptides for the treatment of reperfusion injury (C=2021015130A2). Dr Ruschitzka has not received personal payments by pharmaceutical companies or device manufacturers in the last 3 years; the Department of Cardiology (University Hospital of Zurich/University of Zurich) has received research, educational, and/or travel grants from Abbott, Abiomed, Alexion, Amgen, AstraZeneca, At the Limits Ltd., Bayer, Berlin Heart, B. Braun, Biosense Webster, Biosensors Europe AG, Biotronik, BMS, Boehringer Ingelheim, Boston Scientific, Bracco, Cardinal Health Switzerland, Concept Medical, Corteria, CSL, Daiichi Sankyo, Diatools AG, Edwards Lifesciences, Guidant Europe NV (BS), Hamilton Health Sciences, IHF, Innosuisse, Johnson/Johnson, Kaneka Corporation, Kantar, Kiniksa, Labormedizinisches Zentrum, MedAlliance, Medical Education Global Solutions, Medtronic, MicroPort, MSD, Mundipharma Medical Company, Novartis, Novo Nordisk, Orion, Pfizer, Quintiles Switzerland Sarl, Recor Medical, Roche Diagnostics, Roche Pharma, Sahajanand IN, Sanofi, Sarstedt AG, Servier, SIS Medical, Sorin CRM SAS, SSS International Clinical Research, Stromal, Terumo Deutschland, Trama Solutions, V-Wave, Vascular Medical, Vifor, Wissens Plus, and ZOLL. Dr Schäfer has received grants, consulting fees, honoraria, and personal fees for consultancies, trial committee work, and/or lectures from Abbott Vascular, Edwards Lifesciences, and Polares Medical. Dr Schulze has received grants from Boehringer Ingelheim, Abiomed Inc, Edwards Lifesciences Inc, Cytosorb Inc, and Boston Scientific; and has received consulting fees and/or honoraria from Bayer, AstraZeneca, Daiichi- Sankyo, Novartis, Actelion, Roche, Sanofi, Pharmacosmos, Medtronic, Thoratec, Boehringer Ingelheim, HeartWare, Coronus, Abbott, Boston Scientific, St. Jude Medical, Abiomed, and DGK, and trial committee work for Abbott, Abiomed. Dr Spargias has received fees for proctoring for Abbott Vascular. Dr Vahanian has participated on a data safety monitoring board for Edwards Lifesciences, VenusTech, and Mayo Clinic. Dr Zamorano has received personal payments or honoraria from Viatris, Bayer, and Novartis. Dr Zeiher has received grants or contracts from or served on scientific advisory boards for AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr Koehler has received grants for Project 5G-MedCamp from the German Federal Ministry of Economics and climate protection (BMWK) and grants for projects RESKRIVER and 6 G Health; consulting fees and/or payments or honoraria from BIOTRONIK, Boehringer Ingelheim, Sanofi Germany GmbH, Novartis Germany (till 2022), and AMGEN Germany (in 2021). Dr Lainscak has received a grant from Slovenian Research Agency; and has received honoraria from Novartis, Boehringer Ingelheim, and AstraZeneca. Drs Mezilis and Theofilogiannakos have received support from Abbott for attending meetings. Dr Chrissoheris has received fees for proctoring for Abbott Vascular and Edwards Lifesciences; and has received honoraria from Edwards Lifesciences. Dr Papadopoulos has received consulting fees and honoraria from GE Healthcare. Dr Smolka has received fees for proctoring for Abbott Vascular. Dr Wojakowski has received consulting fees and/or honoraria from Abbott Vascular, Medtronic, and Edwards Lifesciences. Dr Reczuch has received honoraria for lectures from Abbott. Dr Pinto has received consulting fees and/or honoraria from Boehringer Ingelheim, Daichi-Sankyo, Novartis, Servier, Vifor, and Zydus; and participated on advisory boards for Medtronic, Novartis, Servier, and Vifor. Dr Adamo has received honoraria from Abbott Vascular and Edwards Lifesciences. Dr Ruf has received fees proctoring and consulting for Abbott Laboratories and Edwards Lifesciences. Dr Hasenfuß has received personal fees from AstraZeneca, Boehringer, Corvia, Impulse Dynamics, Novartis, Pfizer, and Servier; and has served on trial committees for AstraZeneca, Boehringer, Corvia (no honoraria), Impulse Dynamics, Novartis, Servier, and Vifor Pharma. Dr Schillinger has received consulting and lecture fees and travel expenses from Abbott Vascular. Dr Anker has received grants and personal fees from Vifor and Abbott Vascular; has received personal fees for consultancies, trial committee work, and/or lectures from Actimed, AstraZeneca, Bayer, Bioventrix, Boehringer Ingelheim, Brahms, Cardiac Dimensions, Cardior, Cordio, CVRx, Cytokinetics, Edwards Lifesciences, Farraday Pharmaceuticals, GSK, HeartKinetics, Impulse Dynamics, Medtronic, Novartis, Novo Nordisk, Occlutech, Pfizer, Regeneron, Relaxera, Repairon, Scirent, Sensible Medical, Servier, Vectorious, and V-Wave; and is named as coinventor of two patent applications regarding MR-proANP (DE 102007010834 & DE 102007022367), but he does not benefit personally from the related issued patents. 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.)

Background: Data on the benefits of cardiac resynchronization therapy (CRT) in patients with severe heart failure symptoms are limited. We investigated the relative effects of CRT in patients with ambulatory New York Heart Association (NYHA) IV versus III functional class at the time of device implantation., Methods and Results: In this meta-analysis, we pooled patient-level data from the MIRACLE (Multicenter InSync Randomized Clinical Evaluation), MIRACLE-ICD (Multicenter InSync Implantable Cardioversion Defibrillation Randomized Clinical Evaluation), and COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trials. Outcomes evaluated were time to the composite end point of the first heart failure hospitalization or all-cause mortality, and time to all-cause mortality alone. The association between CRT and outcomes was evaluated using a Bayesian hierarchical Weibull survival regression model. We assessed if this association differed between NYHA III and IV groups by adding an interaction term between CRT and NYHA class as a random effect. A sensitivity analysis was performed by including data from RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure). Our pooled analysis included 2309 patients. Overall, CRT was associated with a longer time to heart failure hospitalization or all-cause mortality (adjusted hazard ratio [aHR], 0.79 [95% credible interval [CI], 0.64-0.99]; posterior probability or P =0.044), with a similar association with time to all-cause mortality (aHR, 0.78 [95% CI, 0.59-1.03]; P =0.083). Associations of CRT with outcomes were not significantly different for those in NYHA III and IV classes (ratio of aHR, 0.72 [95% CI, 0.30-1.27]; P =0.23 for heart failure hospitalization/mortality; ratio of aHR, 0.70 [95% CI, 0.35-1.34]; P =0.27 for all-cause mortality alone). The sensitivity analysis, including RAFT data, did not show a significant relative CRT benefit between NYHA III and IV classes., Conclusions: Overall, there was no significant difference in the association of CRT with either outcome for patients in NYHA functional class III compared with functional class IV.

Aims: Haemodynamic monitoring using implantable pressure sensors reduces the risk of heart failure (HF) hospitalizations. Patient self-management (PSM) of haemodynamics in HF has the potential to personalize treatment, increase adherence, and reduce the risk of worsening HF, while lowering clinicians' burden., Methods and Results: The VECTOR-HF I and IIa studies are prospective, single-arm, open-label clinical trials assessing safety, usability and performance of left atrial pressure (LAP)-guided HF management using PSM in New York Heart Association class II and III HF patients. Physician-prescribed LAP thresholds trigger patient self-adjustment of diuretics. Primary endpoints include the ability to perform LAP measurements and transmit data to the healthcare provider (HCP) interface and the patient guidance application, and safety outcomes. This is an interim analysis of 13 patients using the PSM approach. Over 12 months, no procedure- or device-related major adverse cardiovascular or neurological events were observed, and there were no failures to obtain measurements from the sensor and transmit the data to the HCP interface and the patient guidance application. Patient adherence was 91.4%. Using PSM, annualized HF hospitalization rate significantly decreased compared to a similar period prior to PSM utilization (0 admissions vs. 0.69 admissions over 11.84 months, p = 0.004). At 6 months, 6-min walk test distance and the Kansas City Cardiomyopathy Questionnaire overall summary score demonstrated significant improvement., Conclusions: Interim findings suggest that PSM using a LAP monitoring system is feasible and safe. PSM is associated with high patient adherence, potentially improving HF patients' functional status, quality of life, and limiting HF hospitalizations., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Clinical trials are vital for assessing therapeutic interventions. The associated data monitoring committees (DMCs) safeguard patient interests and enhance trial integrity, thus promoting timely, reliable evaluations of those interventions. We face an urgent need to recruit and train new DMC members. The HFC (Heart Failure Collaboratory), a multidisciplinary public-private consortium of academics, trialists, patients, industry representatives, and government agencies, is working to improve the clinical trial ecosystem. The HFC aims to improve clinical trial efficiency and quality by standardizing concepts, and to help meet the demand for experienced individuals on DMCs by creating a standardized approach to training new members. This paper discusses the HFC's training workshop, and an apprenticeship model for new DMC members. It describes opportunities and challenges DMCs face, along with common myths and best practices learned through previous experiences, with an emphasis on data confidentiality and need for quality independent statistical reporting groups., Competing Interests: Funding Support and Author Disclosures Dr Fleming has received consulting fees from the National Institutes of Health, the World Health Organization, the Food and Drug Administration, and the pharmaceutical and biotech industry in the design, monitoring, and analysis of clinical trials; and he has received fees for serving on several industry-sponsored Data Monitoring Committees (DMCs). Dr Wittes has received compensation for her membership on several DMCs sponsored by industry, government, and not-for-profit organizations; and has received consulting fees from a variety of pharmaceutical and medical device companies. Dr Bristow is the President/CEO/Director at ARCA biopharma. Dr Rockhold has received consulting fees from Intercept, Clover, and Inventprise; has received compensation for serving on several industry-sponsored DMCs; and holds stock in Clover, GSK, Athira, Spence, Adaptic, and Doctor Evidence. Dr Claggett has received consulting fees from Alnylam, Axon, Cardior, Cardurion, CVRx, Cytokinetics, Intellia, and Rocket. Dr Abraham has received consulting fees from Boehringer Ingelheim, Cardionomic, Zoll Respicardia, scPharmaceuticals, Sensible Medical, and Vectorious; has received salary support from V-Wave Medical; and has served as a speaker for Edwards Lifesciences. Dr Lindenfeld has received consulting fees from Abbott, ADI, Alleviant, Amgen, AstraZeneca, Axon, Boston Scientific, Cordio, CVRx, Cytokinetics, Edwards Lifesciences, Medtronic, Merck, VWave, Vascular Dynamics, Vectorious, and Whiteswell; and has received grants from Analog Devices Inc, AstraZeneca, and Volumetrix. Dr DeMets has received consulting fees from the National Institutes of Health, the U.S. Food and Drug Administration, and the pharmaceutical and medical device industry on the design, monitoring, and analysis of clinical trials; and he has received compensation for serving on several recent industry-sponsored data and safety monitoring committees or steering committees including AstraZeneca, Bristol Meyers Squib, GSK, Merck, Boston Scientific, Medtronic, USONA, LivaNova, AnthosTherapy, ARCA biopharma, Duke Clinical Research Institute, and the Population Health Research Institute of Hamilton Ontario. 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.)

The frequency and effectiveness of repeat mitral valve interventions (RMVI) after transcatheter edge-to-edge repair (TEER) for secondary mitral regurgitation (MR) are unknown. We aimed to examine the rate of and outcomes after RMVI after TEER in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial. Only 3.9% of COAPT trial patients required a repeat mitral valve intervention during 4-year follow-up which was successful in 90% of cases but was associated with an increased rate of heart failure (HF) hospitalizations (HFH). The COAPT trial randomized HF patients with severe secondary MR to TEER with the MitraClip device plus guideline-directed medical therapy (GDMT) versus GDMT alone. We evaluated the characteristics and outcomes of patients who had an RMVI during 4-year follow-up. A MitraClip implant was attempted in 293 patients randomized to TEER+GDMT, 10 of whom underwent an RMVI procedure (9 repeat TEER and 1 surgical mitral valve replacement) after 4 years of follow-up (cumulative incidence 3.90%, 95% confidence interval [CI] 2.08 to 7.08; median 182 days after the initial procedure). Patients with RMVI had larger mitral annular diameters, fewer clips implanted, and were more likely to have ≥3+MR at discharge compared with those without RMVI. Reasons for RMVI included failed index procedure because of difficult transseptal puncture (n = 2) or tamponade (n = 1); residual or recurrent severe MR after an initially successful procedure (n = 5); partial clip detachment (n = 1); and site-assessed mitral stenosis (n = 1). RMVI was successful in 8/10 (80%) patients. Patients who underwent RMVI had higher 4-year rates of HFH but similar mortality compared with those without RMVI. The annualized incidence rates of all HFH in patients who underwent RMVI were 234 events per 100 person-years (95% CI 139 to 395) pre-RMVI and 46 per 100 person-years (95% CI 25 to 86) post-RMVI as compared with 32 events per 100 patient-years (95% CI 28 to 36) in patients without RMVI. The rate ratio of HFH was reduced after RMVI in patients who underwent RMVI (0.20, 95% CI 0.09 to 0.45). In conclusion, the cumulative incidence of RMVI after 4 years was 3.9% in patients who underwent TEER for severe secondary MR in the COAPT trial. Patients who underwent RMVI were at increased risk of HFH which was reduced after the RMVI procedure. Clinical Trial Registration: Clinical Trial Name: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (The COAPT Trial) (COAPT) ClinicalTrial.gov Identifier: NCT01626079 URL:https://clinicaltrials.gov/ct2/show/NCT01626079., Competing Interests: Declaration of competing interest Dr. Shahim is supported by Region Stockholm clinical postdoctoral appointment (FoUI- FoUI-969615), Swedish Heart-Lung Foundation (Grants 20220524 and 20190322) and the Swedish Research Council (grant 2022-01472). Dr. Cohen reports grant funding and consulting income from Edwards Lifesciences, Medtronic, Abbott, and Boston Scientific. Dr. Asch is the Director of the Core Laboratories at MedStar Health Research Institute, which has institutional contracts (no personal compensation) with Abbott, Neovasc, Ancora, Mitralign, Medtronic, Boston Scientific, Edwards Lifesciences, Biotronik, and Livanova. Dr. Bax reports that his institution, The Department of Cardiology (LUMC, The Netherlands), has received research grants from Medtronic, Biotronik, Edwards Lifesciences, and Boston Scientific; and has received speaker fees from Abbott Vascular. Dr. George reports consultant fees for Edwards Lifesciences. Dr. Ben-Yehuda has received grants to the Cardiovascular Research Foundation from Uppsala Clinical Research Center, Uppsala University Hospital, Uppsala, Sweden for core laboratory and data center analyses. Dr. Kar has received consulting fees from and is an advisory board member for Boston Scientific; has received consulting fees from and has stock equity options in Valcare; and has received consulting fees from WL Gore and Medtronic. Dr. Lim has received research grant support from Abbott, Boston Scientific, Edwards, and Medtronic; has received consultant fees from Philips, Valgen, Venus, and WL Gore; and is an advisory board member for Ancora and Venus. Dr. Saxon is a speaker and proctor for Abbott Vascular. Dr. Lindenfeld reports research grant support from AstraZeneca; and consultant fees from Abbott Vascular, CVRx, Edwards Lifesciences, ResMed, Relypsa, Boehringer Ingelheim and V-Wave. Dr Abraham reports research grant support from Abbott Vascular, and National Institutes of Health – National Heart, Lung, and Blood Institute (National Institutes of Health 1 UG3/UH3 HL140144-01, 8/1/2018–7/31/2022), “Impact of Low Flow Nocturnal Oxygen Therapy on Hospital Readmission/Mortality in Patients with Heart Failure and Central Sleep Apnea (LOFT-HF)”; consulting income from Abbott Vascular; and speaker honoraria from Impulse Dynamics. Dr. Mack served as co-primary investigator for the PARTNER Trial for Edwards Lifesciences and COAPT trial for Abbott; served as study chair for the Apollo trial for Medtronic. Dr. Stone has received speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, Abbott; has served as a consultant to Daiichi Sankyo, Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, Millennia BioPharma; and has equity/options from Ancora, Cagent, Applied Therapeutics, BioStar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, Xenter. Dr. Stone's daughter is an employee at IQVIA. Institutional disclosure: Dr. Stone's employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo and V-wave., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Cardiogenic shock is a morbid complication of heart disease that claims the lives of more than 1 in 3 patients presenting with this syndrome. Supporting a unique collaboration across clinical specialties, federal regulators, payors, and industry, the American Heart Association volunteers and staff have launched a quality improvement registry to better understand the clinical manifestations of shock phenotypes, and to benchmark the management patterns, and outcomes of patients presenting with cardiogenic shock to hospitals across the United States., Methods: Participating hospitals will enroll consecutive hospitalized patients with cardiogenic shock, regardless of etiology or severity. Data are collected through individual reviews of medical records of sequential adult patients with cardiogenic shock. The electronic case record form was collaboratively designed with a core minimum data structure and aligned with Shock Academic Research Consortium definitions. This registry will allow participating health systems to evaluate patient-level data including diagnostic approaches, therapeutics, use of advanced monitoring and circulatory support, processes of care, complications, and in-hospital survival. Participating sites can leverage these data for onsite monitoring of outcomes and benchmarking versus other institutions. The registry was concomitantly designed to provide a high-quality longitudinal research infrastructure for pragmatic randomized trials as well as translational, clinical, and implementation research. An aggregate deidentified data set will be made available to the research community on the American Heart Association's Precision Medicine Platform. On March 31, 2022, the American Heart Association Cardiogenic Shock Registry received its first clinical records. At the time of this submission, 100 centers are participating., Conclusions: The American Heart Association Cardiogenic Shock Registry will serve as a resource using consistent data structure and definitions for the medical and research community to accelerate scientific advancement through shared learning and research resulting in improved quality of care and outcomes of shock patients., Competing Interests: Dr Jessup, S. Costello, Jennifer Hall, M. Isler, C. Rutan are employees of the American Heart Association. A. Aringo is a recent employee of the American Heart Association. David 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, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals Inc., Roche, Siemens Healthcare Diagnostics Inc., Softcell Medical Limited, The Medicines Company, Zora Biosciences; as well he has received consulting fees from Abbott, ARCA Biopharma, InCarda, Inflammatix, Merck, Novartis, and Roche Diagnostics. Dr Drakos serves as a consultant for Abbott Laboratories and is receiving research support from Novartis, National Heart Lung and Blood Institute, AHA, US Department of Veterans Affairs Merit and the Nora Eccles Treadwell Foundation. Dr Kilic serves as a speaker/consultant for Abiomed, Abbott, Livanova, and 3ive. Dr Kormos is an employee of Abbott Laboratories. Dr Lindenfeld is receiving research support from AstraZeneca and Volumetrix and consulting fees from Abbott, Alleviant,AstraZeneca, Axon, Boston Scientific, CVRx, Merck, Medtronic, Whiteswell, Vascular Dynamics, VWave. Dr Lombardi is an employee of Getinge.

Aim: The RESHAPE-HF2 trial is designed to assess the efficacy and safety of the MitraClip device system for the treatment of clinically important functional mitral regurgitation (FMR) in patients with heart failure (HF). This report describes the baseline characteristics of patients enrolled in the RESHAPE-HF2 trial compared to those enrolled in the COAPT and MITRA-FR trials., Methods and Results: The RESHAPE-HF2 study is an investigator-initiated, prospective, randomized, multicentre trial including patients with symptomatic HF, a left ventricular ejection fraction (LVEF) between 20% and 50% with moderate-to-severe or severe FMR, for whom isolated mitral valve surgery was not recommended. Patients were randomized 1:1 to a strategy of delivering or withholding MitraClip. Of 506 patients randomized, the mean age of the patients was 70 ± 10 years, and 99 of them (20%) were women. The median EuroSCORE II was 5.3 (2.8-9.0) and median plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 2745 (1407-5385) pg/ml. Most patients were prescribed beta-blockers (96%), diuretics (96%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (82%) and mineralocorticoid receptor antagonists (82%). The use of sodium-glucose cotransporter 2 inhibitors was rare (7%). Cardiac resynchronization therapy (CRT) devices had been previously implanted in 29% of patients. Mean LVEF, left ventricular end-diastolic volume and effective regurgitant orifice area (EROA) were 31 ± 8%, 211 ± 76 ml and 0.25 ± 0.08 cm 2 , respectively, whereas 44% of patients had mitral regurgitation severity of grade 4+. Compared to patients enrolled in COAPT and MITRA-FR, those enrolled in RESHAPE-HF2 were less likely to have mitral regurgitation grade 4+ and, on average, HAD lower EROA, and plasma NT-proBNP and higher estimated glomerular filtration rate, but otherwise had similar age, comorbidities, CRT therapy and LVEF., Conclusion: Patients enrolled in RESHAPE-HF2 represent a third distinct population where MitraClip was tested in, that is one mainly comprising of patients with moderate-to-severe FMR instead of only severe FMR, as enrolled in the COAPT and MITRA-FR trials. The results of RESHAPE-HF2 will provide crucial insights regarding broader application of the transcatheter edge-to-edge repair procedure in clinical practice., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Inadequate inclusion in clinical trial enrollment may contribute to health inequities by evaluating interventions in cohorts that do not fully represent target populations., Objectives: The aim of this study was to determine if characteristics of patients with heart failure (HF) enrolled in a pivotal trial are associated with who receives an intervention after approval., Methods: Demographics from 2,017,107 Medicare patients hospitalized for HF were compared with those of the first 10,631 Medicare beneficiaries who received implantable pulmonary artery pressure sensors. Characteristics of the population studied in the pivotal CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) clinical trial (n = 550) were compared with those of both groups. All demographic data were analyzed nationally and in 4 U.S. regions., Results: The Medicare HF cohort included 80.9% White, 13.3% African American, 1.9% Hispanic, 1.3% Asian, and 51.5% female patients. Medicare patients <65 years of age were more likely to be African American (33%) and male (58%), whereas older patients were mostly White (84%) and female (53%). Forty-one percent of U.S. HF hospitalizations occurred in the South; demographic characteristics varied significantly across all U.S. regions. The CHAMPION trial adequately represented African Americans (23% overall, 35% <65 years of age), Hispanic Americans (2%), and Asian Americans (1%) but underrepresented women (27%). The trial's population characteristics were similar to those of the first patients who received pulmonary artery sensors (82% White, 13% African American, 1% Asian, 1% Hispanic, and 29% female)., Conclusions: Demographics of Centers for Medicare and Medicaid Services beneficiaries hospitalized with HF vary regionally and by age, which should be considered when defining "adequate" representation in clinical studies. Enrollment diversity in clinical trials may affect who receives early application of recently approved innovations., Competing Interests: Funding Support and Author Disclosures Abbott provided resources for access and analyses of CMS claims data and demographic information from the CHAMPION trial. Dr Adamson is an employee of Abbott. Dr Echols is a consultant to Abbott. Dr DeFilippis serves on a clinical trial committee for Abiomed. Dr Morris has received research funding from the Agency for Healthcare Research and Quality (HS026081), the American Heart Association, Google, and Merck; and has received consulting fees from Abbott, Acorai, Boehringer Ingelheim, Eli Lilly, Cytokinetics, Edwards Lifesciences, Ionis, Merck, and Regeneron. Dr Bennett has received consulting fees and speaker honoraria from Abbott. Dr Abraham has received consulting fees from Abbott Vascular, AquaPass, Boehringer Ingelheim, Impulse Dynamics, Sensible Medical Innovations, V-Wave, and Zoll Respicardia. Dr Lindenfeld has received consulting and/or research support from Abbott, AstraZeneca, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards Lifesciences, Impulse Dynamics, Merck, Medtronic, V-Wave, Vifor, and Volumetrix. Dr Teerlink has received research support from 3ive Labs, AstraZeneca, Bayer, Boehringer Ingelheim, Cardurion, Cytokinetics, EBR Systems, Edwards Lifesciences, Impulse Dynamics, Kaiser Permanente, LivaNova, Medtronic, Myovant Sciences, the Patient-Centered Outcomes Research Institute, RECARDIO, and V-Wave; and is a consultant for 3ive Labs, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardurion, CorHepta, Cytokinetics, Daiichi-Sankyo, EBR Systems, Edwards Lifesciences, Eli Lilly Impulse Dynamics, JuvLabs, Kaiser Permanente, LivaNova, Medtronic, Myovant Sciences, Novartis, the Patient-Centered Outcomes Research Institute, Pfizer, ReCor Medical, Regeneron, Reprieve, Tectonic, V-Wave, Verily, ViCardia, and Windtree Therapeutics. Dr O’Connor has received research funding from Merck; and has received consulting fees from Bayer and Dey. Dr Connolly is an employee of Abbott. Dr Li is an employee of Abbott. Dr. Vaduganathan has received research grant support from, served on advisory boards for, or has had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer, Baxter Healthcare, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and has participated on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer, Occlutech, and Impulse Dynamics. Dr Batchelor has received consulting fees from Boston Scientific, Medtronic, Edwards Lifesciences, V-Wave, Chiesi, Abbott, and Idorsia; and has received research support from Abbott and Boston Scientific. Dr McCants has received consulting fees and speaker honoraria from Abbott. 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.)

Background: The implications of pulmonary vein (PV) flow patterns in patients with heart failure (HF) and mitral regurgitation (MR) are uncertain. We examined PV flow patterns in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) trial (NCT01626079), in which patients with HF and moderate-to-severe or severe functional MR were randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip device plus guideline-directed medical therapy (GDMT) vs. GDMT alone. We sought to evaluate the prognostic utility of baseline PV systolic flow reversal (PVSFR) in HF patients with severe MR and to determine whether the presence of PVSFR can discriminate patients most likely to benefit from TEER in COAPT trial patients., Methods: Patients were categorized by the echocardiographic core laboratory-assessed baseline presence of PVSFR. Two-year outcomes were examined according to PVSFR and treatment., Results: Baseline PV flow patterns were evaluable in 526/614(85.7%) patients, 48.9% of whom had PVSFR. Patients with PVSFR had more severe MR, reduced stroke volume and cardiac output, greater right ventricular dysfunction, and worse hemodynamics. By multivariable analysis, PVSFR was not an independent predictor of 2-year all-cause death, or heart failure hospitalization (HFH). The reductions in the 2-year rates of all-cause death and HFH with TEER compared with GDMT alone were similar in patients with and without PVSFR (P interaction = 0.40 and 0.12, respectively). The effect of TEER on improving Kansas City Cardiomyopathy Questionnaire scores and 6-minute walk distance were also independent of PVSFR., Conclusions: In the COAPT trial, PVSFR identified HF patients with severe MR and more advanced heart disease. Patients with and without PVSFR had consistent reductions in mortality, HFH, and improved quality-of-life and functional capacity after TEER., Clinical Trial Registration: ClinicalTrial.gov IdentifierNCT01626079., (© 2024 The Author(s).)

Background: Women might benefit more than men from cardiac resynchronization therapy (CRT) and do so at shorter QRS durations., Objective: This meta-analysis was performed to determine whether sex-based differences in CRT effects are better accounted for by height, body surface area (BSA), or left ventricular end-diastolic dimension (LVEDD)., Methods: We analyzed patient-level data from CRT trials (MIRACLE, MIRACLE ICD, MIRACLE ICD II, REVERSE, RAFT, COMPANION, and MADIT-CRT) using bayesian hierarchical Weibull regression models. Relationships between QRS duration and CRT effects were examined overall and in sex-stratified cohorts; additional analyses indexed QRS duration by height, BSA, or LVEDD. End points were heart failure hospitalization (HFH) or death and all-cause mortality., Results: Compared with men (n = 5628), women (n = 1439) were shorter (1.62 [interquartile range, 1.57-1.65] m vs 1.75 [1.70-1.80] m; P < .001), with smaller BSAs (1.76 [1.62-1.90] m 2 vs 2.02 [1.89-2.16] m 2 ; P < .001). In adjusted sex-stratified analyses, the reduction in HFH or death was greater for women (hazard ratio, 0.54; credible interval, 0.42-0.70) than for men (hazard ratio, 0.77; credible interval, 0.66-0.89; P interaction = .009); results were similar for all-cause mortality even after adjustment for height, BSA, and LVEDD. Sex-specific differences were observed only in nonischemic cardiomyopathy. The effect of CRT on HFH or death was observed at a shorter QRS duration for women (126 ms) than for men (145 ms). Indexing QRS duration by height, BSA, or LVEDD attenuated sex-specific QRS duration thresholds for the effects of CRT on HFH or death but not on mortality., Conclusion: Although body size partially explains sex-specific QRS duration thresholds for CRT benefit, it is not associated with the magnitude of CRT benefit. Indexing QRS duration for body size might improve selection of patients for CRT, particularly with a "borderline" QRS duration., (Copyright © 2024. Published by Elsevier Inc.)

Aims: Carotid baroreflex activation therapy (BAT) restores baroreflex sensitivity and modulates the imbalance in cardiac autonomic function in patients with heart failure with reduced ejection fraction (HFrEF). We tested the hypothesis that treatment with BAT significantly reduces cardiovascular mortality and heart failure morbidity and provides long-term safety and sustainable symptomatic improvement., Methods and Results: BeAT-HF was a prospective, multicentre, randomized, two-arm, parallel-group, open-label, non-implanted control trial. New York Heart Association (NYHA) class III subjects, ejection fraction ≤35%, previous heart failure hospitalization or N-terminal pro-B-type natriuretic peptide (NT-proBNP) >400 pg/ml, no class I indication for cardiac resynchronization therapy and NT-proBNP <1600 pg/ml were randomized to BAT plus optimal medical management (BAT group) or optimal medical management alone (control). The primary endpoint was cardiovascular mortality and HF morbidity; additional pre-specified endpoints included durability of safety, quality of life (QOL), exercise capacity (6-min hall walk distance [6MHWD]), functional status (NYHA class), hierarchical composite win ratio, freedom from all-cause death, left ventricular assists device (LVAD) implantation, heart transplant. Overall, 323 patients had 332 primary events, median follow-up was 3.6 years/patient. Both primary endpoint (rate ratio 0.94, 95% confidence interval [CI] 0.57-1.57; p = 0.82) and components of the primary endpoints were not significantly different between BAT and control. The system- and procedure-related major adverse neurological and cardiovascular event-free rate remained 97% throughout the trial. Symptom improvement (QOL, 6MHWD, NYHA class, all nominal p < 0.001) in the BAT group was durable in time, sustainable in extent. Win ratio (1.26, 95% CI 1.02-1.58) and freedom from all-cause death, LVAD implantation, heart transplant (hazard ratio 0.66, 95% CI 0.43-1.01) favoured the BAT group but did not reach statistical significance., Conclusion: The BeAT-HF primary endpoint was neutral; however, BAT provided safe, effective, and sustainable improvements in HFrEF patient's functional status, 6MHWD and QOL., (© 2024 CVRx and The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Heart failure (HF) outcomes remain poor despite optimal guideline-directed medical therapy (GDMT). We assessed safety, effectiveness, and transthoracic echocardiographic (TTE) outcomes during the 12 months after Ventura shunt implantation in the RELIEVE-HF open-label roll-in cohort., Methods and Results: Eligibility required symptomatic HF despite optimal GDMT with ≥1 HF hospitalization in the prior year or elevated natriuretic peptides. The safety endpoint was device-related major adverse cardiovascular or neurological events at 30 days, compared to a prespecified performance goal. Effectiveness evaluations included the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline, 1, 3, 6, and 12 months and TTE at baseline and 12 months. Overall, 97 patients were enrolled and implanted at 64 sites. Average age was 70 ± 11 years, 97% were in New York Heart Association class III, and half had left ventricular ejection fraction (LVEF) ≤40%. The safety endpoint was achieved (event rate 0%, p < 0.001). KCCQ overall summary score was improved by 12-16 points at all follow-up timepoints (all p < 0.004), with similar outcomes in patients with reduced and preserved LVEF. At 12 months, left ventricular end-systolic and end-diastolic volumes were reduced (p = 0.020 and p = 0.038, respectively), LVEF improved (p = 0.009), right ventricular end-systolic and end-diastolic areas were reduced (p = 0.001 and p = 0.030, respectively), and right ventricular fractional area change (p < 0.001) and tricuspid annular plane systolic excursion (p < 0.001) improved., Conclusion: Interatrial shunting with the Ventura device was safe and resulted in favourable clinical effects in patients with HF, regardless of LVEF. Improvements of left and right ventricular structure and function were consistent with reverse myocardial remodelling. These results would support the potential of this shunt device as a treatment for HF., (© 2024 European Society of Cardiology.)

Aims: Patients with heart failure usually have several other medical conditions that might alter the effects of interventions. We investigated whether the burden of comorbidity modified the clinical response to cardiac resynchronization therapy (CRT)., Methods and Results: Original patient-level data from eight randomized trials exploring the effects of CRT versus no CRT were pooled (BLOCK-HF, MIRACLE, MIRACLE-ICD, MIRACLE-ICD II, RAFT, COMPANION, MADIT-CRT and REVERSE). A prior history of the following comorbidities was considered: episodic or persistent atrial fibrillation (n = 920), coronary artery disease (n = 3732), diabetes (n = 2171), and hypertension (n = 3353). Patients were classified into three groups based on the number of comorbidities: 0, 1-2, or ≥3. The outcomes of interest were time to all-cause mortality and time to the composite outcome of heart failure hospitalization (HFH) or all-cause mortality. Outcomes were evaluated within each comorbidity group using a Bayesian hierarchical Weibull survival regression model. Of 6324 patients, 970 (15%) had no comorbidities, 4052 (64%) had 1-2 and 1302 (21%) had ≥3 comorbidities. The adjusted hazard ratio (aHR) for CRT versus no CRT for all-cause mortality in the overall cohort was 0.79 (95% credible interval [CI] 0.68-0.93) (p = 0.010); for no comorbidities the aHR was 0.54 (95% CI 0.34-0.86), for 1-2 comorbidities was 0.81 (95% CI 0.67-0.97) and for ≥3 comorbidities was 0.83 (95% CI 0.64-1.07) (no significant interaction between CRT and comorbidity burden: p = 0.13). For the endpoint of HFH or all-cause mortality, the aHR for the overall cohort was 0.74 (95% CI 0.65-0.84) (p = 0.001), for no comorbidities was 0.69 (95% CI 0.50-0.94), for 1-2 comorbidities was 0.77 (95% CI 0.66-0.90) and for ≥3 comorbidities was 0.68 (95% CI 0.55-0.82) (no significant interaction between CRT and comorbidity burden: p = 0.081)., Conclusion: In a meta-analysis of patient-level data from eight major trials, the totality of evidence suggests that CRT reduces HFH and/or all-cause mortality even when several comorbid diseases are present., Clinical Trial Registration: NCT00271154, NCT00251251, NCT00267098, NCT00180271., (© 2023 European Society of Cardiology.)

Heart failure (HF) is a complex syndrome traditionally classified by left ventricular ejection fraction (LVEF) cutpoints. Although LVEF is prognostic for risk of events and predictive of response to some HF therapies, LVEF is a continuous variable and cutpoints are arbitrary, often based on historical clinical trial enrichment decisions rather than physiology. Holistic evaluation of the treatment effects for therapies throughout the LVEF range suggests the standard categorization paradigm for HF merits modification. The multidisciplinary Heart Failure Collaboratory reviewed data from large-scale HF clinical trials and found that many HF therapies have demonstrated therapeutic benefit across a large range of LVEF, but specific treatment effects vary across that range. Therefore, HF should practically be classified by association with an LVEF that is reduced or not reduced, while acknowledging uncertainty around the precise LVEF cutpoint, and future research should evaluate new therapies across the continuum of LVEF., Competing Interests: Funding Support and Author Disclosures Dr Ibrahim has received consulting fees from Cytokinetics. Dr McMurray discloses payments to his employer, Glasgow University, for his work on clinical trials, consulting, and other activities: Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardurion, Cytokinetics, Dal-Cor, GlaxoSmithKline, Ionis, KBP Biosciences, Novartis, Pfizer, and Theracos; and personal payments: Abbott, Alkem Metabolics, Eris Lifesciences, Hikma, Ionis, Lupin, ProAdWise Communications, Sun Pharmaceuticals, and Servier. Dr Lindenfeld has received consulting fees from Abbott, Alleviant, Boston Scientific, Cordio, CRVx, Edwards Lifesciences, Medtronic, Merck, Whiteswell, Vascular Dynamics, and V-Wave. Dr Bozkurt has received consulting fees from Amgen, AstraZeneca, Bristol Myers Squibb, scPharmaceuticals, Baxter, Sanofi, Relypsa, Vifor, Roche, and Boehringer Ingelheim; has served on the steering committees of Relypsa and Renovacor; has served on a Clinical Event Committee for Abbott Pharmaceuticals; and has served on the Data Safety Monitoring Board for LivaNova Pharmaceuticals. Dr Bristow has served as a director, officer, partner, advisor, consultant, or trustee for ARCA biopharma; has received research grants from the American Heart Association and National Institute of Allergy and Infectious Diseases; and has received personal payments from ARCA biopharma. Dr Butler has received consulting fees from Boehringer Ingelheim, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, Sanofi, Sequana Medical, V-Wave Ltd, and Vifor; and is a Trial Executive Committee member of the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance (trial sponsor). Dr Carson has received consulting fees from Boehringer Ingelheim and IQVIA related to work on Clinical Events Committees. Dr Felker has received research grants from the National Heart, Lung, and Blood Institute, American Heart Association, Amgen, Bayer, BMS, Novartis, Daxor, Merck, Cytokinetics, and CSL-Behring; has acted as a consultant to Novartis, Amgen, BMS, Cytokinetics, Innolife, Medtronic, Cardionomic, Boehringer Ingelheim, American Regent, Abbott, AstraZeneca, Regeneron, Reprieve, Myovant, Sequana, Windtree Therapuetics, Rocket Pharma, and Whiteswell; and has served on clinical endpoint committees/data safety monitoring boards for Amgen, Merck, Medtronic, EBR Systems, V-Wave, and LivaNova. Dr Murillo is an employee and stockholder of UnitedHealth Group. Dr Kondo has received grants from the Uehara Memorial Foundation and the Japanese Heart Failure Society Tsuchiya Foundation for research activity at the University of Glasgow; and has received lecture fees from Ono Pharmaceutical Co, Ltd, Otsuka Pharmaceutical Co, Ltd, Novartis Pharma K.K., AstraZeneca K.K., Bristol Myers Squibb Co, Abiomed Japan K.K., and Boehringer Ingelheim. Dr Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung and Blood Institute, Novartis, Sanofi Pasteur, and Theracos; and has consulted for Akros, Alnylam, Amgen, AstraZeneca, Bayer, BMS, Cardior, Corvia, Cytokinetics, Gilead, GlaxoSmithKline, Ironwood, Merck, MyoKardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, and Tenaya. Dr Abraham has received consulting fees from Boehringer Ingelheim, Cardionomic, Zoll Respicardia, scPharmaceuticals, Sensible Medical, and Vectorious; has received salary support from V-Wave Medical; and has served as a speaker for Edwards Lifesciences. Dr O’Connor has received grant or research support from Merck; and consulting fees from Merck, Bayer, and Abiomed. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Published by Elsevier Inc.)

Background: Transcatheter edge-to-edge repair (TEER) improved outcomes in patients with heart failure (HF) and severe secondary mitral regurgitation (SMR) compared with guideline-directed medical therapy (GDMT) alone regardless of the severity of baseline left ventricular ejection fraction (LVEF). The study aimed to evaluate the effect of early changes in LVEF after TEER and GDMT alone in patients with HF and severe SMR., Methods: Within the COAPT trial, we evaluated outcomes according to changes in LVEF from baseline to 30 days. The primary outcome was all-cause death or HF hospitalization (HFH) between 30 days and 2 years., Results: Among 432 patients with paired echocardiographic data, 182 (42.1%) had increased LVEF (LVEF change 6.0% ± 4.9%) and 250 (57.9%) had a decrease or no change in LVEF (LVEF change -6.6% ± 5.6%) from baseline to 30 days. LVEF at 30 days increased more frequently with GDMT alone compared with TEER plus GDMT (51.4% vs 33.0%; P = .0001). Between 30 days and 2 years, there were no significant differences in death or HFH in the increase LVEF and the decrease LVEF groups (58.8% vs 51.4%; multivariable-adjusted HR, 0.97; 95% CI, 0.87-1.08; P = .59). TEER plus GDMT reduced the 30-day to 2-year rate of death or HFH compared with GDMT alone consistently in patients with increase LVEF and decrease LVEF (P int = 0.75)., Conclusions: Among patients with HF and severe SMR, early improvements in LVEF were more frequent with GDMT alone compared with TEER plus GDMT but were not associated with subsequent outcomes at 2 years. TEER reduced death or HFH during 2-year follow-up irrespective of early LVEF changes., (© 2024 The Author(s).)

Background: Trials evaluating implantable hemodynamic monitors to manage patients with heart failure (HF) have shown reductions in HF hospitalizations but not mortality. Prior meta-analyses assessing mortality have been limited in construct because of an absence of patient-level data, short-term follow-up duration, and evaluation across the combined spectrum of ejection fractions., Objectives: The purpose of this meta-analysis was to determine whether management with implantable hemodynamic monitors reduces mortality in patients with heart failure and reduced ejection fraction (HFrEF) and to confirm the effect of hemodynamic-monitoring guided management on HF hospitalization reduction reported in previous studies., Methods: The patient-level pooled meta-analysis used 3 randomized studies (GUIDE-HF [Hemodynamic-Guided Management of Heart Failure], CHAMPION [CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients], and LAPTOP-HF [Left Atrial Pressure Monitoring to Optimize Heart Failure Therapy]) of implantable hemodynamic monitors (2 measuring pulmonary artery pressures and 1 measuring left atrial pressure) to assess the effect on all-cause mortality and HF hospitalizations., Results: A total of 1,350 patients with HFrEF were included. Hemodynamic-monitoring guided management significantly reduced overall mortality with an HR of 0.75 (95% CI: 0.57-0.99); P = 0.043. HF hospitalizations were significantly reduced with an HR of 0.64 (95% CI: 0.55-0.76); P < 0.0001., Conclusions: Management of patients with HFrEF using an implantable hemodynamic monitor significantly reduces both mortality and HF hospitalizations. The reduction in HF hospitalizations is seen early in the first year of monitoring and mortality benefits occur after the first year., Competing Interests: Funding Support and Author Disclosures Abbott (Abbott Park, Illinois) funded the CHAMPION, LAPTOP-HF, and GUIDE-HF studies. Dr Lindenfeld has received consulting fees from Abbott, Alleviant, AstraZeneca, Axon, Biotronik, Boston Scientific, CVRx, Edwards Lifesciences, Medtronic, Merck, Vascular Dynamics, Vectorious, and VWave; and has received grants from AstraZeneca. Dr Costanzo is a consultant for Abbott. Dr Zile has received research funding from Novartis; and has been a consultant for Novartis, Abbott, Boston Scientific, CVRx, EBR, Endotronix, Ironwood, Merck, Medtronic, and Myokardia V Wave. Dr Ducharme has received consulting fees from Abbott, Akcea, Alnylam, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Pfizer, and Sanofi; and has received grants from AstraZeneca, Bayer, Corvia, Eidos, Novartis, Novo Nordisk, Pfizer, and Servier. Dr Troughton has received research grants from Health Research Council of New Zealand; has received consulting fees from Merck, Bayer, American Regent, and Roche Diagnostics; and has received honoraria payments from Roche Diagnostics. Drs Maisel and Paul are consultants for Abbott. Dr Mehra is a consultant for Natera, Paragonix, Moderna, Janssen, Broadview Ventures, Mesoblast, and Baim Institute for Clinical Research; is a consultant for Abbott; has served on the Clinical Events Committee for GUIDE-HF through the Baim Institute for Clinical Research; and has stock in NuPulseCV, Leviticus, Transmedics, and FineHeart. Dr Sears has received research grants from Medtronic and Zoll; is a consultant for Abbott, Medtronic, and Milestone Pharmaceutical; and has received personal fees from Medtronic and Zoll. Dr Smart has received research grants from Amgen; and is a consultant for Abbott. Dr Johnson, Mr Henderson, and Dr Adamson are full-time employees and shareholders for Abbott. Dr Desai has received institutional research grants from Abbott, Alnylam, AstraZeneca, Bayer, and Novartis; and is a consultant for Abbott, Alnylam, AstraZeneca, Axon Therapeutics, Avidity, Biofourmis, Boston Scientific, Cytokinetics, GlaxoSmithKline, Medpace, Merck, Novartis, Parexel, Regeneron, Roche, and Verily. Dr Abraham has received personal fees from Zoll Respicardia, Cardionomic, WhiteSwell, AquaPass, Cordio, Vectorious, Impulse Dynamics, and Edwards Lifesciences; and has personal equity in V-Wave Medica. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: The Breakthrough Devices Program of the US Food and Drug Administration has accelerated the development and evaluation of medical devices for patients with heart failure. One such device is the Optimizer Smart System, which the US Food and Drug Administration approved in 2019., Methods and Results: The Optimizer device was evaluated in a pivotal randomized clinical trial (FIX-HF-5C [Confirmatory Randomized Trial Evaluating the Optimizer System]) that leveraged Bayesian borrowing of external data to reduce the sample size and determine therapeutic device benefit versus continued medical therapy. Bayesian borrowing is explained in the context of the FIX-HF-5C trial, including an overview of the statistical methodologies, regulatory considerations, and interpretations of trial results., Conclusions: The US Food and Drug Administration Breakthrough Devices Program and novel Bayesian statistical methodology accelerated the path to regulatory approval and patient access to a potentially lifesaving device and may serve as a model for future clinical trials.

Despite remarkable improvements in the management of heart failure (HF), HF remains one of the most rapidly growing cardiovascular condition resulting in a substantial burden on healthcare systems worldwide. In clinical practice, however, a relevant proportion of patients are treated with suboptimal combinations and doses lower than those recommended in the current guidelines. Against this background, it remains important to identify new targets and investigate additional therapeutic options to alleviate symptoms and potentially improve prognosis in HF. Therefore, non-pharmacological interventions targeting autonomic imbalance in HF have been evaluated. This paper aims to review the physiology, available clinical data, and potential therapeutic role of device-based neuromodulation in HF., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: Cardiac implantable electrical devices are able to affect kidney function through hemodynamic improvements. The cardiac contractility modulation (CCM) is a device-based therapy option for patients with symptomatic chronic heart failure (HF) despite optimized medical treatment. The long-term cardiorenal interactions for CCM treated patients are yet to be described., Methods: CCM recipients (n = 187) from the Mannheim Cardiac Contractility Modulation Observational Study (MAINTAINED) were evaluated in the long-term (up to 60 months) for changes in serum creatinine, estimated glomerular filtration rate (eGFR), other surrogate markers of kidney function, and the chronic kidney disease (CKD) stage distribution. With regard to kidney function at baseline, the patients were furthermore grouped to either advanced CKD (aCKD, CKD stage ≥3, eGFR≤59 mL/min/1.73 m2, n = 107) or preserved kidney function and mild CKD (pCKD, CKD stages 1-2, eGFR≥60 mL/min/1.73 m2, n = 80). The groups were compared for differences regarding kidney function, New York Heart Association classification (NYHA), biventricular systolic function, HF hospitalizations and other parameters in the long-term (60 months)., Results: CKD stage distribution remained stable during the entire follow-up (p = 0.65). An increase in serum creatinine (1.47 ± 1 vs. 1.6±1 mg/dL) with a corresponding decline of eGFR (58.2 ± 23.4 vs. 54.2 ± 24.4 mL/min/1.73 m2, both p &lt; 0.05) were seen after 60 months but not before for the total cohort, which was only significant in pCKD patients in terms of group comparison. Mean survival (54.3 ± 1.3 vs. 55.3 ± 1.2 months, p = 0.53) was comparable in both groups. Improvements in NYHA (3.11 ± 0.46 vs. 2.94 ± 0.41-2.28 ± 0.8 vs. 1.94 ± 0.6) and LVEF (24.8 ± 7.1 vs. 22.9 ± 6.6-31.1 ± 11.4 vs. 35.5 ± 11.1%) were likewise similar after 60 months (both p &lt; 0.05). The aCKD patients suffered from more HF hospitalizations and ventricular tachycardias during the entire follow-up period (both p &lt; 0.05)., Conclusions: The kidney function parameters and CKD stage distribution might remain stable in CCM treated HF patients in the long-term, who experience improvements in LVEF and functional status, regardless of their kidney function before. An impaired kidney function might be associated with further cardiovascular comorbidities and more advanced HF before CCM, and could be an additional risk factor of HF complications afterward., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Cardiac resynchronization therapy (CRT) reduces heart failure hospitalizations (HFH) and mortality for guideline-indicated patients with heart failure (HF). Most patients with HF are aged ≥70 years but such patients are often under-represented in randomized trials., Methods: Patient-level data were combined from 8 randomized trials published 2002-2013 comparing CRT to no CRT (n = 6,369). The effect of CRT was estimated using an adjusted Bayesian survival model. Using age as a categorical (<70 vs ≥70 years) or continuous variable, the interaction between age and CRT on the composite end point of HFH or all-cause mortality or all-cause mortality alone was assessed., Results: The median age was 67 years with 2436 (38%) being 70+; 1,554 (24%) were women; 2,586 (41%) had nonischemic cardiomyopathy and median QRS duration was 160 ms. Overall, CRT was associated with a delay in time to the composite end point (adjusted hazard ratio [aHR] 0.75, 95% credible interval [CI] 0.66-0.85, P = .002) and all-cause mortality alone (aHR of 0.80, 95% CI 0.69-0.96, P = .017). When age was treated as a categorical variable, there was no interaction between age and the effect of CRT for either end point (P > .1). When age was treated as a continuous variable, older patients appeared to obtain greater benefit with CRT for the composite end point (P for interaction = .027) with a similar but nonsignificant trend for mortality (P for interaction = .35)., Conclusion: Reductions in HFH and mortality with CRT are as great or greater in appropriately indicated older patients. Age should not be a limiting factor for the provision of CRT., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Acute decompensated heart failure (ADHF) is one of the most common reasons for hospitalizations or urgent care and is associated with poor outcomes. Therapies shown to improve outcomes are limited, however, and innovation in pharmacologic and device-based therapeutics are therefore actively being sought. Standardizing definitions for ADHF and its trajectory is complex, limiting the generalizability and translation of clinical trials to effect clinical care and policy change. The Heart Failure Collaboratory is a multistakeholder organization comprising clinical investigators, clinicians, patients, government representatives (including U.S. Food and Drug Administration and National Institutes of Health participants), payors, and industry collaborators. The following expert consensus document is the product of the Heart Failure Collaboratory convening with the Academic Research Consortium, including members from academia, the U.S. Food and Drug Administration, and industry, for the purposes of proposing standardized definitions for ADHF and highlighting important endpoint considerations to inform the design and conduct of clinical trials for drugs and devices in this clinical arena., Competing Interests: Funding Support and Author Disclosures Dr Lala is a Speakers Bureau member for Abiomed, Cytokinetics, Novartis, and Zoll; and performs contracted research for Merck. Dr Bozkurt has received consulting fees from Amgen, AstraZeneca, Bristol Myers Squibb, scPharmaceuticals, Baxter, Sanofi, Relypsa, Vifor, Roche, and Boehringer Ingelheim; has served on the steering committees of Relypsa and Renovacor; has served on a Clinical Event Committee for Abbott Pharmaceuticals; and has served on the Data Safety Monitoring Board for LivaNova Pharmaceuticals. Dr Burkhoff receives institutional grant support from Ancora Heart, Axon Medical, and Edwards Lifesciences; and receives consulting fees from AquaPass, Axon, BackBeat Medical, BioMind, Corvia Medical, Impulse Dynamics, and Therox/Zoll. Dr Costanzo has served as a Board of Directors member for Nuwellis; has received research grants from Bayer, Novartis, and V-WAVE to the Midwest Cardiovascular Institute; and is an Associated Editor for the Journal of the American College of Cardiology. Dr Felker has received research grants from the National Heart, Lung, and Blood Institute, the American Heart Association, Amgen, Bayer, BMS, Novartis, Daxor, Merck, Cytokinetics, and CSL Behring; has acted as a consultant to Novartis, Amgen, BMS, Cytokinetics, Innolife, Medtronic, Cardionomic, Boehringer Ingelheim, American Regent, Abbott, AstraZeneca, Regeneron, Reprieve, Myovant, Sequana, Windtree Therapeutics, Rocket Pharma, and WhiteSwell; and has served on clinical endpoint committees/data safety monitoring boards for Amgen, Merck, Medtronic, EBR Systems, V-WAVE, and LivaNova. Dr Filippatos is a committee member of trials and registries sponsored by Amgen, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor Pharma; is a Senior Consulting Editor for JACC Heart Failure; and has received research support from the European Union. Dr Konstam has been a consultant for FIRE1, Pfizer, Luitpold, Cardurion, Cytogenetics, and Boehringer Ingelheim. Dr McMurray reports payments to his employer, Glasgow University, for his work on clinical trials, consulting, and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardurion, Cytokinetics, DalCor, GSK, Ionis, KBP Biosciences, Novartis, Pfizer, and Theracos; and personal payments from Abbott, Alkem Metabolics, Eris Lifesciences, Hikma, Ionis, Lupin, ProAdWise Communications, Sun Pharmaceuticals, and Servier. Dr Mentz is a consultant to Abbott, Medtronic, Boston Scientific, and Zoll. Dr Metra has received personal fees of minimal amounts in the last 3 years: from Actelion as member of the Data Monitoring Committee of sponsored clinical trials; from Amgen, LivaNova, Servier, and Vifor Pharma as member of Executive Committees of sponsored clinical trials; and from AstraZeneca, Abbott Vascular, Bayer, Boehringer Ingelheim, and Edwards Therapeutics for participation on advisory boards and/or for speeches at sponsored meetings. Dr Solomon has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, NeuroTronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has served as a consultant for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, 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, and Akros. Dr Teerlink is a consultant for 3iveLabs, Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Merck, Novartis, Verily, ViCardia, and Windtree Therapeutics; and has received research grants from 3ive Labs, Abbott, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Cardurion, Cytokinetics, EBR Systems, Edwards, Medtronic, Novartis, V-WAVE, ViCardia, and Windtree Therapeutics. Dr Abraham has received consulting fees from Boehringer Ingelheim, Cardionomic, Zoll Respicardia, scPharmaceuticals, Sensible Medical; Vectorious Salary support from V-WAVE Medical; and has served as a speaker for Edwards Lifesciences. Dr O’Connor has received grant or research support from Merck; and consulting fees from Merck, Bayer, and Abiomed. 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.)

The prevalence of heart failure continues to increase throughout the world. This rise in diagnoses corresponds with high rates of hospitalization, patient and caregiver fatigue, and ever-increasing economic costs. While numerous investigations have been undertaken in the past looking into remote monitoring or telemedicine strategies, they were unable to show an improvement in clinical outcomes with use. Invasive hemodynamic monitoring in the ambulatory setting has been an area of focus for the last several decades as a possible proactive strategy aiding in the evaluation and management of the heart failure population. Several large, randomized trials have not only shown the safety of a pulmonary artery pressure sensor in the heart failure population but have also confirmed the efficacy of pulmonary artery pressure-guided heart failure management in reducing rates of heart failure hospitalizations. Additional novel implantable devices are in various stages of development and clinical investigation and aim to further help aid in the management of this complex patient population. Future strategies are emerging and include the increased development of wearable devices as well as novel technologies to assess hemodynamics and volume status., (© 2023 The Author(s).)

Background: Risk scores may identify patients with mitral regurgitation (MR) who are at risk for adverse events, but who may still benefit from transcatheter edge-to-edge repair (TEER). We sought to cross-validate the MitraScore and COAPT risk score to predict adverse events in patients undergoing TEER., Methods: MitraScore validation was carried out in the COAPT population which included 614 patients with FMR who were randomized 1:1 to guideline-directed medical therapy (GDMT) with or without TEER and were followed for 2 years. Validation of the COAPT risk score was carried out in 1007 patients from the MIVNUT registry of TEER-treated patients with both FMR and degenerative MR who were followed for a mean of 2.1 years. The predictive value was assessed using the area under the receiver operating characteristic curve (AUC) plots. The primary outcome was all-cause mortality., Results: The MitraScore had fair to good predictive accuracy for mortality in the overall COAPT trial population (AUC, 0.67); its accuracy was higher in patients treated with TEER (AUC, 0.74) than GDMT alone (AUC, 0.65). The COAPT risk score had fair predictive accuracy for death in the overall MitraScore cohort (AUC, 0.64), which was similar in patients with FMR and degenerative MR (AUC, 0.64 and 0.66, respectively). There was a consistent benefit of treatment with TEER plus GDMT compared with GDMT alone in the COAPT trial population across all MitraScore risk strata., Conclusions: The COAPT risk score and MitraScore are simple tools that are useful for the prediction of 2-year mortality in patients eligible for or undergoing treatment with TEER., (© 2023 The Author(s).)

The Shock Academic Research Consortium is a multi-stakeholder group, including representatives from the US Food and Drug Administration and other government agencies, industry, and payers, convened to develop pragmatic consensus definitions useful for the evaluation of clinical trials enrolling patients with cardiogenic shock, including trials evaluating mechanical circulatory support devices. Several in-person and virtual meetings were convened between 2020 and 2022 to discuss the need for developing the standardized definitions required for evaluation of mechanical circulatory support devices in clinical trials for cardiogenic shock patients. The expert panel identified key concepts and topics by performing literature reviews, including previous clinical trials, while recognizing current challenges and the need to advance evidence-based practice and statistical analysis to support future clinical trials. For each category, a lead (primary) author was assigned to perform a literature search and draft a proposed definition, which was presented to the subgroup. These definitions were further modified after feedback from the expert panel meetings until a consensus was reached. This manuscript summarizes the expert panel recommendations focused on outcome definitions, including efficacy and safety., Competing Interests: Disclosures Dr Waksman reports serving on the advisory boards of Abbott Vascular, Boston Scientific, Medtronic, Philips IGT, and Pi-Cardia Ltd.; consulting for Abbott Vascular, Biotronik, Boston Scientific, Cordis, Medtronic, Philips IGT, Pi-Cardia Ltd., Swiss Interventional Systems/SIS Medical AG, Transmural Systems Inc., and Venous MedTech; receiving institutional grant support from Amgen, Biotronik, Boston Scientific, Chiesi, Medtronic, and Philips IGT; and investing in MedAlliance and Transmural Systems Inc. Dr Morrow is a member of the Thrombolysis in Myocardial Infarction 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. Dr Morrow has received consulting fees from Abbott Laboratories, ARCA Biopharma, Inflammatix, Merck & Co., Novartis, and Roche Diagnostics. Dr Spitzer reports institutional contracts for which he receives no direct compensation with Boston Scientific, Cardiawave, Edwards Lifesciences, Medtronic, Occlutech US, LLC, Shanghai Microport Medical Co. Ltd., NVT GmBH, Pie Medical Imaging, Siemens Healthcare GmBH. Dr Dickert receives research funding from the National Institutes of Health’s Agency for Healthcare Research and Quality and Data Safety Monitoring Board service for National Institutes of Health and Patient-Centered Outcomes Research Institute–funded studies. Dr Dickert reports consulting for and research funding from Abiomed, Inc. Dr Mebaaza reports receiving research grants, consulting, and receiving speaker fees from Roche Diagnostics and receiving speaker fees from Merck. Dr Fan reports personal fees from ALung Technologies, Aerogen, Baxter, GE Healthcare, Inspira, Vasomune, and Zoll Medical outside the submitted work. Dr Kormos is an employee (Division Vice President Global Medical Affairs Heart Failure) of Abbott Laboratories. Dr Proudfoot has received institutional funding from Abbott Vascular and BD Biosciences, all outside of the submitted work. Dr Simonton is an employee (Chief Medical Officer) of Abiomed, a Johnson & Johnson Company. Dr Damluji received a mentored patient-oriented research career development award from the National Heart, Lung, and Blood Institute (K23-HL153771-01). Dr Cutlip reports consulting for and research funding from Corvia Medical, MedAlliance, and Abiomed. Dr Nichol reports salary support from Medic One Foundation via the University of Washington; research funding from National Institutes of Health, Centers for Disease Control and Prevention, Abiomed Inc, Zoll Medical, RCE Technologies Inc., Zoll Circulation Inc., and Vapotherm Inc; and consulting for BrainCool AB, CPR Therapeutics Inc., Heartbeam Inc., Invero Health LLC, Kestra Medical Technologies Inc., and Orixha Inc.

Aims: Adjustment of treatment based on remote monitoring of pulmonary artery (PA) pressure may reduce the risk of hospital admission for heart failure (HF). We have conducted a meta-analysis of large randomized trials investigating this question., Methods and Results: A systematic literature search was performed for randomized clinical trials with PA pressure monitoring devices in patients with HF. The primary outcome of interest was the total number of HF hospitalizations. Other outcomes assessed were urgent visits leading to treatment with intravenous diuretics, all-cause mortality, and composites. Treatment effects are expressed as hazard ratios, and pooled effect estimates were obtained applying random effects meta-analyses. Three eligible randomized clinical trials were identified that included 1898 outpatients in New York Heart Association functional classes II-IV, either hospitalized for HF in the prior 12 months or with elevated plasma NT-proBNP concentrations. The mean follow-up was 14.7 months, 67.8% of the patients were men, and 65.8% had an ejection fraction ≤40%. Compared to patients in the control group, the hazard ratio (95% confidence interval) for total HF hospitalizations in those randomized to PA pressure monitoring was 0.70 (0.58-0.86) (P = .0005). The corresponding hazard ratio for the composite of total HF hospitalizations, urgent visits and all-cause mortality was 0.75 (0.61-0.91; P = .0037) and for all-cause mortality 0.92 (0.73-1.16). Subgroup analyses, including ejection fraction phenotype, revealed no evidence of heterogeneity in the treatment effect., Conclusion: The use of remote PA pressure monitoring to guide treatment of patients with HF reduces episodes of worsening HF and subsequent hospitalizations., Competing Interests: Conflict of interest P.R.D.C., S.P.R., E.B. report no conflict of interest to declare. R.A.d.B. has received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals GmbH, Ionis Pharmaceuticals, Inc., Novo Nordisk, and Roche; and has had speaker engagements with Abbott, AstraZeneca, Bayer, Bristol Myers Squibb, Novartis, and Roche. J.G. has received consulting fees from Applied Therapeutics, Amarin, Boehringer-Ingelheim, Biosensors, Cardialysis, Edwards Lifesciences, MVRx and Whiteswell and reimbursement of travel expenses from Abbott. W.T.A. has received personal fees from Abbott, Boehringer-Ingelheim, Edwards Lifesciences, Impulse Dynamics, Sensible Medical, Vectorious Medical Technolgoies, V-Wave Medical, and Zoll Respicardia. P.S.J. received consulting fees, advisory board fees and lecture fees from Novartis; advisory board fees from Cytokinetics; and grant support from Boehringer Ingelheim. J.J.V.M.M. received payments through Glasgow University from work on clinical trials, consulting and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardurion, Cytokinetics, DalCor, GSK, KBP Biosciences, Novartis, Pfizer and Theracos, and personal payments from Abbott, Hikma, Ionis, Sun Pharmaceuticals and Servier. J.J.V.M.M. and P.S.J. are supported by a British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217). J.J.B. received independent research grant from Abbott for ISS and has had speaker engagement or advisory boards in the past 5 years with Astra Zeneca, Abbott, Boehringer-Ingelheim, Bayer, Daiichi Sankyo, Novartis and Vifor., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aim: Although education in self-management is thought to be an important aspect of the care of patients with heart failure, little is known about whether self-rated knowledge of self-management is associated with outcomes. The aim of this study was to assess the relationship between patient-reported knowledge of self-management and clinical outcomes in patients with heart failure and reduced ejection fraction (HFrEF)., Methods and Results: Using individual patient data from three recent clinical trials enrolling participants with HFrEF, we examined patient characteristics and clinical outcomes according to responses to the 'self-efficacy' questions of the Kansas City Cardiomyopathy Questionnaire. One question quantifies patients' understanding of how to prevent heart failure exacerbations ('prevention' question) and the other how to manage complications when they arise ('response' question). Self-reported answers from patients were pragmatically divided into: poor (do not understand at all, do not understand very well, somewhat understand), fair (mostly understand), and good (completely understand). Cox-proportional hazard models were used to evaluate time-to-first occurrence of each endpoint, and negative binomial regression analysis was performed to compare the composite of total (first and repeat) heart failure hospitalizations and cardiovascular death across the above-defined groups. Of patients (n = 17 629) completing the 'prevention' question, 4197 (23.8%), 6897 (39.1%), and 6535 (37.1%) patients had poor, fair, and good self-rated knowledge, respectively. Of those completing the 'response' question (n = 17 637), 4033 (22.9%), 5463 (31.0%), and 8141 (46.2%) patients had poor, fair, and good self-rated knowledge, respectively. For both questions, patients with 'poor' knowledge were older, more often female, and had a worse heart failure profile but similar treatment. The rates (95% confidence interval) per 100 person-years for the primary composite outcome for 'poor', 'moderate' and 'good' self-rated knowledge in answer to the 'prevention' question were 12.83 (12.11-13.60), 12.08 (11.53-12.65) and 11.55 (11.00-12.12), respectively, and for the 'response' question were 12.88 (12.13-13.67), 12.22 (11.60-12.86) and 11.56 (11.07-12.07), respectively. The lower event rates in patients with 'good' self-rate knowledge were accounted for by lower rates of cardiovascular (and all-cause) death and not hospitalization for worsening heart failure., Conclusions: Poor patient-reported 'self-efficacy' may be associated with higher rates of mortality. Evaluation of knowledge of 'self-efficacy' may provide prognostic information and a guide to which patients may benefit from further education about self-management., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)