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Background: Hemocompatibility-related adverse events affect patients after left ventricular assist device (LVAD) implantation but are hard to predict., Objectives: Dynamic risk modeling with a multistate model can predict risk of gastrointestinal bleeding (GIB), stroke, or death in ambulatory patients., Methods: This was a secondary analysis of the MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) trial. HeartMate 3 LVAD recipients who survived to hospital discharge and were followed for up to 2 years. A total of 145 variables were included in the multistate model with multivariate logistic regression. Model performance was assessed with the area under the curve in a holdout validation cohort. A risk stratification tool was created by dividing patients into categories of predicted risk using the final model variables and associated OR., Results: Among 2,056 LVAD patients, the median age was 59.4 years (20.4% women, 28.6% Black). At 2 years, the incidence of GIB, stroke, and death was 25.6%, 6.0%, and 12.3%, respectively. The multistate model included 39 total variables to predict risk of GIB (16 variables), stroke (10 variables), and death (19 variables). When ambulatory patients were classified according to their risk category, the 30-day observed event rate in the highest risk group for GIB, stroke, or death was 26.9%, 1.8%, and 4.8%, respectively. The multistate model predicted GIB, stroke, and death at any 30-day period with an area under the curve of 0.70, 0.69, and 0.86, respectively., Conclusions: The multistate model informs 30-day risk in ambulatory LVAD recipients and allows recalculation of risk as new patient-specific data become available. The model allows for accurate risk stratification that predicts impending adverse events and may guide clinical decision making. (MOMENTUM 3 IDE Clinical Study Protocol; NCT02224755)., Competing Interests: Funding Support and Author Disclosures Abbott is the sponsor of the MOMENTUM 3 studies. Abbott supported an investigator-initiated grant paid to the Inova Heart and Vascular Institute to support this effort; and Abbott has filed a U.S. provisional patent (U.S. Patent Application No. 63/421,450) for the work presented in the paper. Dr Shah is supported by National Institutes of Health K23 Career Development Award 1K23HL143179; has received consulting fees from Procyrion, Merck, and Natera; and grant support has been paid to his institution from Abbott, Roche, Merck, and Bayer. Dr Sayer has received consulting fees from Abbott. Dr Kanwar is on the medical advisory board for Abiomed, CorWave, and CareDx. Dr Cowger has served as a consultant for Abbott, Medtronic, Bioventrix, Endotronix, Bivacor, and Procyrion; and has received grant support and speaker fees from Abbott. Dr Pagani has served as an AD hoc scientific advisor without compensation for FineHeart, Medtronic, CH Biomedical, and Abbott; has served as medical monitor for Abiomed; is a member of the data safety monitoring board for Carmat and the National Heart, Lung, and Blood Institute PumpKIN clinical trial; and is Chair of the Society of Thoracic Surgeons Intermacs Task Force. Dr Mehra has received travel support and consulting fees, paid to Brigham and Women’s Hospital, from Abbott; has received fees for serving on a steering committee from Medtronic and Janssen (Johnson and Johnson); has received fees for serving on a data and safety monitoring board from Mesoblast; has received consulting fees from Natera, Paragonix, Moderna, Baim Institute of Clinical Research, and Broadview Ventures; and has received fees for serving as a scientific board member from NuPulseCV, Leviticus, and FineHeart. Dr Cleveland has received fees from Abbott and Medtronic. Dr Desai is on the speaker’s bureau for Abbott. Drs Lu, Hu, Connolly, and Kormos are employees of Abbott. Dr Uriel is a medical advisory board member for Livemetric, Levitcus, and Revamp; and receives grant support from Abbott, Abiomed, and Fire 1. 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 article 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 American College of Cardiology Foundation. All rights reserved.)

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.)

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 Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory (HFC) and the Academic Research Consortium (ARC) composed of patients, academic investigators from the United States and Europe, the U.S. Food and Drug Administration, the National Institutes of Health, payers, and industry. Members discussed the measure, remote capture, and clinical utility of functional and quality-of-life endpoints for use in clinical trials of heart failure and cardiovascular therapeutics, with the goal of improving the efficiency of heart failure and cardiovascular clinical research, evidence generation, and thereby patient quality of life, functional status, and survival. Assessments of patient-reported outcomes and maximal and submaximal exercise tolerance are standardized and validated, but actigraphy remains inconsistent as a potential endpoint. This paper details those discussions and consensus recommendations., Competing Interests: Funding Support and Author Disclosures The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the FDA or the U.S. Department of Health and Human Services. Dr Abraham has received consulting fees from Boehringer Ingelheim and Zoll Respicardia, speaker honoraria from Impulse Dynamics, salary support from V-Wave Medical, and research support from the U.S. National Institutes of Health/National Heart, Lung, and Blood Institute. Dr Filippatos has received consulting income from Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor; and has received lecture fees from Merck. Dr Lindenfeld has received consulting fees from Novartis, Abbott, ResMed, V-Wave, CVRx, and Cytokinetics. Dr Ahmad has received consulting fees from Amgen, Cytokinetics, Relypsa, and Novartis. Dr Felker has received research grants from the National Heart, Lung, and Blood Institute, the American Heart Association, Amgen, Merck, Cytokinetics, and Roche Diagnostics; and has received consulting fees from Novartis, Amgen, Bristol Myers Squibb, Cytokinetics, Medtronic, Cardionomic, Relypsa, V-Wave, Myokardia, Innolife, EBR Systems, Arena, Abbott, Sphingotec, Roche Diagnostics, Alnylam, LivaNova, Windtree Therapeutics, Rocket Pharma, and SC Pharma. Dr Kitzman has received consulting fees from AstraZeneca, Bayer, Novartis, Merck, Pfizer, Boehringer Ingelheim, AbbVie, DCRI, and Corvia; has received grant support from AstraZeneca, Bayer, and Novartis; and has stock in Gilead. Dr Lewis has received consulting fees from Novartis; and has received institutional research grant support from Amgen, Novartis, and Sanofi. Dr Mentz has received consulting fees from Abbott, Amgen, AstraZeneca, Bayer, Boston Scientific, Janssen, Luitpold, Medtronic, Merck, Novartis, and Sanofi; and has received research grants from Akros, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, GlaxoSmithKline, Gilead, InnoLife, Luitpold/American Reagent, Novartis, Otsuka, ResMed, and the National Institutes of Health (grants U01HL125511-01A1 and R01AG045551-01A1). Dr Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, the National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Sanofi Pasteur, and Theracos; and has received consulting fees from Akros, Alnylam, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Cardior, Corvia, Cytokinetics, Gilead, GlaxoSmithKline, Ironwood, Merck Sharpe & Dohme, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, and Cardiac Dimensions. Dr Teerlink has received consulting fees from Amgen, Bayer, Cytokinetics, Novartis, and Stealth Health; and has received research funding from Abbott, Amgen, Bayer, Bristol Myers Squibb, Novartis, and scPharma. Dr Unger’s employer, Hyman, Phelps & McNamara, has contracts with many companies, some of which are developing treatments for HF. Dr Whellan has received grant support from the National Institutes of Health (grant R01AG045551). Dr Wittes’s employer, Wittes LLC, has contracts with many companies, some of which are developing treatments for HF. Dr Anker has received fees from Abbott, Bayer, Boehringer Ingelheim, Cardiac Dimension, Cordio, Impulse Dynamics, Novartis, Occlutech, Servier, and Vifor Pharma; and has received grant support from Abbott and Vifor Pharma. Dr O’Connor has received grant or research support from Roche Diagnostics and Merck; and has received consulting fees from Merck, Bayer, Bristol Myers Squibb, Abiomed, and Windtree. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Although it is a rare disease, the number of available therapeutic options for treating pulmonary arterial hypertension has increased since the late 1990s, with multiple drugs developed that are shown to be effective in phase 3 randomised controlled trials. Despite considerable advancements in pulmonary arterial hypertension treatment, prognosis remains poor. Existing therapies target pulmonary endothelial dysfunction with vasodilation and anti-proliferative effects. Novel therapies that target proliferative vascular remodelling and affect important outcomes are urgently needed. There is need for additional innovations in clinical trial design so that all emerging candidate therapies can be rigorously studied. Pulmonary arterial hypertension trial design has shifted from short-term submaximal exercise capacity as a primary endpoint, to larger clinical event-driven trial outcomes. Event-driven pulmonary arterial hypertension trials could face feasibility and efficiency issues in the future because increasing sample sizes and longer follow-up durations are needed, which would be problematic in such a rare disease. Enrichment strategies, innovative and alternative trial designs, and novel trial endpoints are potential solutions that could improve the efficiency of future pulmonary arterial hypertension trials while maintaining robustness and clinically meaningful evidence., Competing Interests: Declaration of interests JW received research grants paid to his institution from Janssen, Actelion, Merck, and Bayer; consulting fees paid personally from Janssen; honoraria for lectures from Janssen; payment for expert testimony from Sprigings Intellectual Property Law; travel support from Janssen; and payment for participation in advisory boards from Janssen and Acceleron. AB received grants paid to her institution from Acceleron, Janssen, and MSD; honoraria for lectures from Janssen, MSD, and AOP Orphan; and travel support from Janssen. AP received a training grant from the National Heart, Lung, and Blood Institute paid to his institution; and discloses stock or stock options in Bristol Myers Squibb. DM received research grants paid to his institution from Acceleron, Janssen, and Merck; consulting fees from Acceleron; and honoraria for lectures from Bayer, Janssen, and Merck. FZ has received consulting fees from Amgen, Applied Therapeutics, Bayer, Boehringer Ingelheim, Cellprothera, CVRx, Janssen, Merck, Novartis, AstraZeneca, Cardior, Novo Nordisk, Servier, and Vifor Fresenius; honoraria for lectures from Boehringer Ingelheim, Bayer, and Vifor Fresenius; payment for expert testimony from Hogan Lovells; advisory board payment from Acceleron; holds a leadership role with CardioVascular Clinical Trials; and holds stock or stock options with Cereno, G3 Pharmaceuticals, and Cardior. MG-M received grants paid to her institution from Altavant, Aerovate, Acceleron, Merck, Bayer, and United Therapeutics; consulting fees from Acceleron, Merck, Bayer, Altavant, Janssen, and United Therapeutics; honoraria for continuing medical education from Medscape; advisory board payments from Janssen, Aerovate, and Gilead; and holds leadership roles on the board of directors for the International Society of Heart & Lung Transplantation, Scientific Leadership Committee of the Pulmonary Hypertension Association, and Scientific Advisory Board of United Therapeutics. VM has received grants paid to his institution from Acceleron, Janssen, Sonovie, and United Therapeutics; consulting fees from Acceleron, Aerovate, Altavant, Bayer, Caremark, Civi Biopharma, Corvista, Gossamer Bio, Janssen, Merck, and United Therapeutics; and holds a leadership role on the Board of Directors at Clene. GS received consulting fees from MSD, Bayer, Actelion, and Janssen; payment for lectures from MSD, Bayer, Actelion, and Janssen; and advisory board payments from Acceleron. MH received grants paid to his institution from Acceleron, AOP Orphan, Janssen, Merck, and Shou Ti; consulting fees from Acceleron, Aerovate, Altavant, AOP Orphan, Bayer, Chiesi, Ferrer, Janssen, Merck, MorphogenIX, and United Therapeutics; honoraria for lectures from Janssen and Merck; and advisory board payments from Acceleron, Altavant, Janssen, Merck, and United Therapeutics. KP received research grants from the British Heart Foundation and SPARKS society in 1995–98 for unrelated work, and has no additional interests to declare. All other authors declare no competing interests. Disclaimer: The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the US Food and Drug Administration or the United States Department of Health and Human Services., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Left ventricular assist devices (LVADs) mechanically unload the heart and coupled with neurohormonal therapy can promote reverse cardiac remodeling and myocardial recovery. Minimally invasive LVAD decommissioning with the device left in place has been reported to be safe over short-term follow-up. Whether device retention reduces long-term safety, or sustainability of recovery is unknown., Methods: This is a dual-center retrospective analysis of patients who had achieved responder status (left ventricular ejection fraction, LVEF ≥40% and left ventricular internal diastolic diameter, LVIDd ≤6.0 cm) and underwent elective LVAD decommissioning for myocardial recovery from May 2010 to January 2020. All patients had outflow graft closure and driveline resection with the LVAD left in place. Emergent LVAD decommissioning for an infection or device thrombosis was excluded. Patients were followed with serial echocardiography for up to 3-years. The primary clinical outcome was survival free of heart failure hospitalization, LVAD reimplantation, or transplant., Results: During the study period 515 patients received an LVAD and 29 (5.6%) achieved myocardial recovery, 12 patients underwent total device explantation or urgent device decommissioning, 17 patients underwent elective LVAD decommissioning, and were included in the analysis. Median age of patients at LVAD implantation was 42 years (interquartile range, IQR: 25-54 years), all had a nonischemic cardiomyopathy, and 5 (29%) were female. At LVAD implantation, median LVEF was 10% (IQR: 5%-15%), and LVIDd 6.6 cm (IQR: 5.8-7.1 cm). There were 11 hydrodynamically levitated centrifugal-flow (65%), and 6 axial-flow LVADs (35%). The median duration of LVAD support before decommissioning was 28.7 months (range 13.5-36.2 months). As compared to the turndown study parameters, 1-month post-decommissioning, median LVEF decreased from 55% to 48% (p = 0.03), and LVIDd increased from 4.8 cm to 5.2 cm (p = 0.10). There was gradual remodeling until 6 months, after which there was no statistical difference on follow-up through 3-years (LVEF 42%, LVIDd 5.6 cm). Recurrent infections affected 41% of patients leading to 3 deaths and 1 complete device explant. Recurrent HF occurred in 1 patient who required a transplant. Probability of survival free of HF, LVAD, or transplant was 94% at 1-year, and 78% at 3-years., Conclusions: LVAD decommissioning for myocardial recovery was associated with excellent long-term survival free from recurrent heart failure and preservation of ventricular size and function up to 3-years. Reducing the risk of recurrent infections, remains an important therapeutic goal for this management strategy., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Actigraphy-based measurements of physiologic parameters may enable design of patient-centric heart failure (HF) clinical trials. Recently, the Heart Failure Collaboratory focused on recommendations for meaningful change and use of actigraphy as an end point in HF clinical trials. We aimed to evaluate randomized controlled trials (RCTs) that have quantified the impact of HF interventions using actigraphy., Methods: Using a scoping review strategy, we evaluated the use of actigraphy in HF RCTs. Studies were identified through electronic searches of Embase, OVID Medline, PubMed, and Cochrane Review. Data on trial characteristics and results were collected., Results: We identified 11 RCTs with a total of 1,455 participants. The risk of bias across the included trials was high overall. All trials had the primary outcomes reflecting measures of either physical activity (n = 8), sleep (n = 2), or both (n = 1). Five trials evaluated response to pharmacologic therapies compared with placebo, 3 evaluated physical activity interventions, 2 evaluated group or cognitive therapy, and 1 evaluated sleep-ventilation strategy. Sample sizes ranged from 30 to 619 participants. There was significant heterogeneity relating to device type, body placement site, and handling of missing actigraphy data. Duration of monitoring ranged from 48 hours to 12 weeks. None of the studies evaluating pharmacologic therapies (n = 5) demonstrated a significant improvement of actigraphy-based primary end point measurements., Conclusions: There is significant heterogeneity in the use, methodology, and results of actigraphy-based HF RCTs. Our results highlight the need to develop, standardize, and validate actigraphy-specific outcomes for use in HF clinical trials., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The treatment of heart failure with reduced ejection fraction (HFrEF) has changed considerably over time, particularly with the sequential development of therapies aimed at antagonism of maladaptive biologic pathways, including inhibition of the sympathetic nervous system and the renin-angiotensin aldosterone system. The sequential nature of earlier HFrEF trials allowed the integration of new therapies tested against the background therapy of the time. More recently, multiple heart failure therapies are being evaluated simultaneously, and the number of therapeutic choices for treating HFrEF has grown considerably. In addition, implementation science has lagged behind discovery science in heart failure. Furthermore, given there are currently >200 ongoing clinical trials in heart failure, further complexities are anticipated. In an effort to provide a decision-making framework in the current era of expanding therapeutic options in HFrEF, the Heart Failure Collaboratory convened a multi-stakeholder group, including patients, clinicians, clinical investigators, the U.S. Food and Drug Administration, industry, and payers who met at the U.S. Food and Drug Administration campus on March 6, 2020. This paper summarizes the discussions and expert consensus recommendations., Competing Interests: Author Disclosures Dr. Bhatt has received honorarium from Sanofi Pasteur and is supported by the National Heart, Lung, and Blood Institute T32 postdoctoral training grant T32HL094301. Dr. Abraham has received consulting fees from Abbott, Boehringer Ingelheim, CVRx, Edwards Lifesciences, Respicardia; salary support from V-Wave Medical; and research support from the U.S. National Institutes of Health/National Heart, Lung, and Blood Institute. Dr. Bristow is an employee of ARCA Biopharma. Dr. Felker has received research grants from the National Heart, Lung, and Blood Institute, the American Heart Association, Amgen, Merck, Cytokinetics, and Roche Diagnostics; and has received consulting fees from Novartis, Amgen, Bristol Myers Squibb, Cytokinetics, Medtronic, Cardionomic, Relypsa, V-Wave, MyoKardia, Innolife, EBR Systems, Arena, Abbott, SphingoTec, Roche Diagnostics, Alnylam, LivaNova, Windtree Therapeutics, Rocket Pharma, and SC Pharma. Dr. Fonarow has received consulting from Abbott, Amgen, AstraZeneca, Bayer, CHF Solutions, Edwards, Janssen, Medtronic, Merck, and Novartis. Dr. Greene has received a Heart Failure Society of America/Emergency Medicine Foundation Acute Heart Failure Young Investigator Award funded by Novartis; has received research support from Amgen, AstraZeneca, Bristol Myers Squibb, Merck, and Novartis; has served on advisory boards for Amgen and Cytokinetics; and serves as a consultant for Amgen and Merck. Dr. Lindenfield has received consulting fees from Novartis, Abbott, ResMed, V-Wave, CVRx, and Cytokinetics. Dr. Psotka has received consulting fees from Amgen, Cytokinetics, and Windtree; and grant support from the U.S. Food and Drug Administration. Dr. Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol-Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Neurotronik, Novartis, Respicardia, Sanofi Pasteur, Theracos; and has consulted for Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GlaxoSmithKline, Ironwood, Merck, MyoKardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AOBiome, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, and Tremeau. Dr. Teerlink has received consulting fees from Amgen, Bayer, Cytokinetics, Novartis, and Stealth Health; and research funding from Abbott, Amgen, Bayer, Bristol Myers Squibb, Novartis, and scPharmaceuticals. Dr. Vaduganathan is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (National Institutes of Health/National Center for Advancing Translational Sciences Award UL 1TR002541); serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa; and participates on clinical endpoint committees for studies sponsored by Novartis and the National Institutes of Health. Dr. Wittes reports that the company for which she works, Statistics Collaborative, has contracts with many companies, some of which are developing treatments for HF. Dr. O’Connor has received research support from Roche Diagnostics; has received research support and is a consultant for Merck; is a consultant for Bristol Myers Squibb, Windtree, and Neurotronik; and is a co-owner of BisCardia. Dr. Butler has received personal fees as a consultant from Abbott, Adrenomed, Amgen, Array, AstraZeneca, Bayer, Berlin Cures, Boehringer Ingelheim, Bristol Myers Squib, CVRx, G3 Pharmaceuticals, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, Sanofi, SC Pharma, V-Wave Limited, and Vifor outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory (HFC) and Academic Research Consortium (ARC), comprised of leading heart failure (HF) academic research investigators, patients, United States (US) Food and Drug Administration representatives, and industry members from the US and Europe. A series of meetings were convened to establish definitions and key concepts for the evaluation of HF therapies including optimal medical and device background therapy, clinical trial design elements and statistical concepts, and study endpoints. This manuscript summarizes the expert panel discussions as consensus recommendations focused on populations and endpoint definitions; it is not exhaustive or restrictive, but designed to stimulate HF clinical trial innovation., Competing Interests: Author Disclosures W.T.A. has received consulting fees from Abbott, Boehringer Ingelheim, CVRx, Edwards Lifesciences, Respicardia, and research support from the U.S. National Institutes of Health/National Heart, Lung, and Blood Institute. M.A.P. has received consulting fees from Amgen, Cytokinetics, and Windtree, and grant support from the United States Food and Drug Administration. G.F. has received consulting income from Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor, and lecture fees from Merck. J.L. has received consulting fees from Novartis, Abbott, ResMed, VWave, CVRx, and Cytokinetics. R.M. has received institutional research grant support from Abbott Laboratories, AstraZeneca, Bayer, Beth Israel Deaconess Medical Center, Bristol-Myers Squibb, CSL Behring, Eli Lilly/Daiichi-Sankyo, Medtronic, Novartis Pharmaceuticals, and OrbusNeich; has served on scientific advisory boards of PLx Opco/PLx Pharma, Medtelligence (Janssen Scientific Affairs), and Bristol-Myers Squibb; has served on the executive committees of Janssen Pharmaceuticals and Osprey Medical; has served on the data safety monitoring board of Watermark Research Partners; has served as a consultant for Abbott Laboratories, Abiomed (spouse), Boston Scientific, Cardiovascular Systems, Medscape/Web MD, Siemens Medical Solutions, The Medicines Company (spouse), Regeneron Pharmaceuticals, Roivant Sciences, Spectranetics/Philips/Volcano Corporation, and Sanofi; and has equity in Claret Medical and Elixir Medical Corporation. J.L.J. is a trustee of the American College of Cardiology, is a board member of Imbria Pharmaceuticals, has received grant support from Novartis Pharmaceuticals, Roche Diagnostics, Abbott, Singulex and Prevencio, consulting income from Abbott, Janssen, Novartis, Pfizer, Merck, and Roche Diagnostics, and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Amgen, Boehringer Ingelheim, Janssen, and Takeda. M.A.K. has received consulting fees from Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, and Novartis; and grants and research support from Ironwood and Livanova. M.W.K. has received consulting fees from Abbott Vascular, Angel Medical Systems, Biosensors, CSI, Boston Scientific, Medtronic, OrbusNeich, and St Jude Medical, and has received grant funding from Abbott Vascular, Angel Medical Systems, Boston Scientific, Medtronic, OrbusNeich, Biosensors, CSI, and St Jude Medical. E.F.L. has received consulting fees from Novartis, and institutional research grant support from Amgen, Novartis, and Sanofi. J.P.P. has received grant support from Abbott, the American Heart Association, the Association for the Advancement of Medical Instrumentation, Bayer, Boston Scientific, the National Heart, Lung, and Blood Institute, and Philips, and has received consulting fees from Abbott, Allergan, ARCA Biopharma, Biotronik, Boston Scientific, LivaNova, Medtronic, Milestone, Sanofi, Philips, and Up-to-Date. S.D.S. has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bristol-Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, U.S. National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Sanofi Pasteur, and Theracos; and consulting fees from Akros, Alnylam, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Cardior, Corvia, Cytokinetics, Gilead, GlaxoSmithKline, Ironwood, Merck Sharpe & Dohme, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, and Cardiac Dimensions. J.R.T. has received consulting fees from Amgen, Bayer, Cytokinetics, Novartis, and Stealth Health, and research funding from Abbott, Amgen, Bayer, Bristol-Myers Squibb, Novartis, scPharma. S.D.A. has received clinical trial-related fees from Abbott Vascular, Servier, Vifor, Bayer, Boehringer Ingelheim, Thermo Fisher, Respicardia, and Novartis. C.M.O’C. has received research support from Roche Diagnostics; has received research support and is a consultant for Merck, Bristol-Myers Squibb, Windtree, and Neurotronik, and is a co-owner of Biscardia. All other authors have nothing to disclose. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the United States Food and Drug Administration or the United States Department of Health and Human Services., (Copyright © 2020. Published by Elsevier Inc.)

Objectives: This study sought to demonstrate the statistical and utilitarian properties of restricted mean survival time (RMST) and restricted mean time lost (RMTL) for assessing treatments for heart failure (HF) with reduced ejection fraction., Background: Although the hazard ratio (HR) is the most commonly used measure to quantify treatment effects in HF clinical trials, HRs may be difficult to interpret and require the proportional hazards assumption to be valid. RMST and RMTL are intuitive summaries of groupwise survival that measure treatment effects without model assumptions., Methods: Patient time-to-event data were reconstructed from published landmark HF clinical trial Kaplan-Meier curves. We estimated RMST differences (ΔRMSTs) and RMTL ratios between treatment groups for primary and secondary outcomes, and compared test statistics and effect sizes with proportional hazards models. We fit Weibull estimations to extrapolate trial data to 5 years of treatment., Results: Using RMSTs and RMTLs yielded similar statistical conclusions as HR analysis for a compendium of 16 HF clinical trials including 48,581 patients. RMTL ratios approximated HRs for each trial, but ΔRMSTs provided absolute effect sizes unavailable with HRs. For instance, spironolactone added 2.2 months of life over 34 months of treatment, and dapagliflozin added 0.3 months of life over 24 months of treatment. When normalized to 5-years follow-up with Weibull estimation, spironolactone and dapagliflozin added 6.0 months and 1.8 months of life for patients, respectively., Conclusions: Statistically, RMST and RMTL perform similarly to proportional hazards modeling but may help patients by providing clinically relevant intuitive estimates of treatment effects without prohibitive assumptions., Competing Interests: Author Disclosures Dr. O’Connor has received research support from Roche Diagnostics and Merck; has served as a consultant for Merck, Bristol Myers Squibb, Windtree, and Neurotronik; and is a co-owner of Biscardia. Dr. Psotka has received consulting fees from Amgen, Cytokinetics, and Windtree; and research funding from the U.S. Food and Drug Administration. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Cardiogenic shock is a hemodynamically complex syndrome characterized by a low cardiac output that often culminates in multiorgan system failure and death. Despite recent advances, clinical outcomes remain poor, with mortality rates exceeding 40%. In the absence of adequately powered randomized controlled trials to guide therapy, best practices for shock management remain nonuniform. Emerging data from North American registries, however, support the use of standardized protocols focused on rapid diagnosis, early intervention, ongoing hemodynamic assessment, and multidisciplinary longitudinal care. In this review, the authors examine the pathophysiology and phenotypes of cardiogenic shock, benefits and limitations of current therapies, and they propose a standardized and team-based treatment algorithm. Lastly, they discuss future research opportunities to address current gaps in clinical knowledge., Competing Interests: Author Relationship With Industry Dr. Tehrani has received consulting and speaker honoraria from Medtronic. Dr. Truesdell has received consulting and speaker honoraria from Abiomed. Dr. Damluji was supported by research funding from the Pepper Scholars Program of the Johns Hopkins University Claude D. Pepper Older Americans Independence Center, funded by the National Institute on Aging P30-AG021334. Dr. Batchelor has served as consultant for Boston Scientific, Abbott, Medtronic, and V-Wave. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The mandatory federal pay-for-performance Hospital Readmissions Reduction Program (HRRP) was created to decrease 30-day hospital readmissions by instituting accountability and stimulating quality care and coordination, particularly during care transitions. The HRRP has changed the landscape of hospital readmissions and reimbursement within the United States by imposing substantial Medicare payment penalties on hospitals with higher-than-expected readmission rates. However, the HRRP has been controversial since its inception, particularly in the field of heart failure. Proponents argue that it has reduced national readmission rates, in part by raising awareness and investment in mechanisms to better assist patients during discharge and transitions; opponents contend that it unfairly penalizes hospitals for issues beyond their control, has unintended negative consequences due to incentivizing readmission over survival, that it encourages "gaming" the system, was not tested before implementation, and that it does not specify how hospitals can improve their performance. This paper incorporates the diverse, nuanced, and sometimes divergent interpretations presented during a multifaceted expert clinician discussion regarding the HRRP and heart failure; in cases in which consensus opinions were achieved, they are presented, including regarding potential new iterations of the HRRP for the future. Potential improvements include more comprehensive incorporation of outcomes into the HRRP measure and better risk adjustment to improve equality and fairness., (Copyright © 2020 American College of Cardiology Foundation. All rights reserved.)

The development of treatments for heart failure (HF) is challenged by burdensome clinical trials. Reducing the need for extensive data collection and increasing opportunities for data compatibility between trials may improve efficiency and reduce resource burden. The Heart Failure Collaboratory (HFC) multi-stakeholder consortium sought to create a lean case report form (CRF) for use in HF clinical trials evaluating cardiac devices. The HFC convened patients, clinicians, clinical researchers, the U.S. Food and Drug Administration (FDA), payers, industry partners, and statisticians to create a consensus core CRF. Eight recent clinical trial CRFs for the treatment of HF from 6 industry partners were analyzed. All CRF elements were systematically reviewed. Those elements deemed critical for data collection in HF clinical trials were used to construct the final, harmonized CRF. The original CRFs included 176 distinct data items covering demographics, vital signs, physical examination, medical history, laboratory and imaging testing, device therapy, medications, functional and quality of life assessment, and outcome events. The resulting, minimally inclusive CRF device contains 75 baseline data items and 6 events, with separate modular additions that can be used depending on the additional detail required for a particular intervention. The consensus electronic form is now freely available for use in clinical trials. Creation of a core CRF is important to improve clinical trial efficiency in HF device development in the United States. This living document intends to reduce clinical trial administrative burden, increase evidence integrity, and improve comparability of clinical data between trials., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ventricular assist device (VAD) patients often experience infections, which increase the risk of stroke and mortality. Using the definitions of the International Society for Heart and Lung Transplantation (ISHLT), we have characterized differences in clinical outcomes for categories of infection: VAD-specific (e.g., pump component related); VAD-related (e.g., bloodstream infection, BSI); and non-VAD infections (e.g., pneumonia)., Methods: Querying of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) identified 16,597 continuous-flow VAD recipients. Categories of infection were tested in multivariate models to determine the risk of stroke and death., Results: After implant, 7,046 patients (42%) developed an infection at a median of 69 (interquartile range 12 to 272) days. A majority were non-VAD infections (49%), followed by VAD-related (26%) and VAD-specific infections (25%). BSIs were the most common form of VAD-related infection (92%), and the majority (59%) had no associated infection, that is, idiopathic bacteremia. Internal pump component infections were rare (0.003 event per patient-year [EPPY]). Infected VAD patients had a higher prevalence of stroke compared to patients without an infection (18% vs 11%, p < 0.001). The lowest stroke rate occurred after a VAD-specific infection (0.11 EPPY) compared with VAD-related (0.17 EPPY) and non-VAD infections (0.15 EPPY, p < 0.001). Hemorrhagic strokes were more common than ischemic strokes in all infection groups and highest after a VAD-related infection (0.13 EPPY). One-year survival after an infection was 87% in VAD-specific infections, as compared with VAD-related (71%) and non-VAD infections (72%, p < 0.001)., Conclusions: The ISHLT categorization of VAD infections unveils notable differences in associated risk of stroke and mortality. A re-assessment of transplant prioritization for eligible infected VAD patients may be useful to increase transplant-related survival benefit., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine clinician and scientist involvement in heart failure (HF) clinical research and to describe the challenges of conducting clinical trials in the United States., Background: Improvements in the current capability, potential, and deficiencies of the HF clinical research infrastructure in the United States are needed in order to enhance efficiency and impact., Methods: The Heart Failure Society of America (HFSA) distributed an electronic survey regarding HF clinical trial activity for the purpose of understanding the barriers that exist to conducting high-quality HF clinical research., Results: Overall, 1,794 HFSA members were queried, and 434 members (24%) completed surveys, whereas a total of 7,589 individuals with interest in HF were queried, and 615 completed surveys. Of the respondents, 410 (67%) were actively engaged in HF research and 120 (20%) were interested in research. Most respondents, 270, were physicians (44%); 311 of the total (76% of the total and 80% of physicians) practiced in academic institutions; 333 respondents (81%) had served as principal investigators and 73 (18%) as site coordinators. Respondents active in clinical research usually participated in 1 to 5 trials and enrolled 1 to 20 patients annually. Institutional review board (IRB) approval typically required 3 months, and contract completion required 3 to 6 months per site. The greatest barriers to research were insufficient site budgets, delay in contracting, inability to find participants meeting trial entry criteria, and unavailability of qualified study coordinators., Conclusions: Many U.S. clinical research sites are constrained by budgetary, staffing, and contractual issues. The HFSA Research Network seeks to unify interested sites and deconstruct barriers to permit high-value HF research., (Copyright © 2019 American College of Cardiology Foundation. All rights reserved.)

Objectives: The study sought to review the characteristics of existing patient-reported outcome (PRO) instruments used with chronic heart failure (HF) patients and evaluate their potential to support an approved U.S. Food and Drug Administration (FDA) product label claim., Background: PROs, including symptoms and their associated functional limitations, contribute substantially to HF patient morbidity. PRO measurements capture the patient perspective and can be systematically assessed with structured questionnaires, however rigorous recommendations have been set by the FDA regarding the acceptability of PRO measures as a basis for product label claims., Methods: Extensive searches of databases and specialty guidelines identified PRO instruments used in patients with chronic HF. Information on critical properties recommended by the FDA guidance were systematically extracted and used to evaluate the selected PRO instruments., Results: Nineteen PRO instruments used with chronic HF patients were identified. The Kansas City Cardiomyopathy Questionnaire and Minnesota Living with Heart Failure Questionnaire were the most extensively evaluated and validated in studies of this population. However, judged by criteria listed in the FDA PRO guidance, no existing PRO measure met all of the criteria to support a product label claim in the United States., Conclusions: Currently available chronic HF PRO measures do not fulfill all the recommendations provided in the FDA PRO guidance and therefore may not support an FDA-approved product label claim. Future investigations are merited to develop a PRO measure for use in patients with chronic HF in accordance with the FDA guidance., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Atrial fibrillation is the most common cardiac arrhythmia and is associated with significant morbidity, mortality, and economic cost. Although the benefit of anticoagulation has been well described, control of the underlying rhythm disturbance can be achieved in various ways. Numerous therapeutic options exist and continue to be developed; however, the single best strategy has not been elucidated, and rate or rhythm controlling strategies may both be undertaken. The selection of particular agents to successfully achieve these strategies takes into account patient preference and comorbidity, as well as the efficacy and side effect profiles of the possible medications. This review discusses the evidence behind the various agents typically used to treat atrial fibrillation as well as provides a framework on which to make clinical decisions while initiating and continuing therapy., (Copyright © 2014. Published by Elsevier Inc.)