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NHLBI Working Group: Heart Failure Prevention - Identifying Research Priorities for the Next Decade

Executive Summary

The National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group (WG) on July 14-15, 2011 in Bethesda, MD to discuss future directions of research in heart failure (HF) prevention. Specifically, the focus was to address the prevention of progression of HF from Stage B to C. The WG was composed of researchers with expertise in the basic, clinical, and epidemiological science of HF prevention. These experts were asked to identify the highest priority research gaps and make recommendations for future research strategies to address those gaps. WG members were asked to include approaches that capitalize on current scientific opportunities and focus on areas that require unique NHLBI leadership. The WG members strove to develop both visionary and practical recommendations having short and long-term impact on HF prevention.


HF prevention is an urgent public health need with national and global implications. As the number of patients with HF around the world continues to rise, and health care costs continue to escalate, there is a need to develop novel HF prevention paradigms. The WG identified the following critical research gaps in HF prevention: 1) the need for better animal models to help understand the transition from Stage B to C HF; 2) the need for robust pre-clinical markers of disease; 3) the need for methods to identify which Stage B patients will progress to Stage C HF and beyond to deploy preventive interventions appropriately; 4) the need for more refined screening techniques and approaches; and, 5) the need for randomized trials to test the effectiveness of pharmacological, lifestyle, and adherence interventions in the target population

WG Recommendations:

HF Prevention – Critical Gaps in Basic Science Research

  • Develop appropriate animal models to advance understanding of the different stages of HF progression. Research findings should incorporate data obtained from human tissue studies and be integrated and validated across different animal models presently used in HF research.
  • Investigate the roles and contributions of: 1) pathologic myocyte hypertrophy; 2) matrix remodeling; and, 3) crosstalk among myocytes, vasculature, and matrix in the development of myocardial pathology and the transition from Stage B to Stage C HF.
  • Investigate and integrate the contributions of aging, diabetes, obesity, neural control, ventricular-arterial interactions (both systemic and pulmonary), cardio-renal regulation, and systemic activation of oxidative stress/inflammation in model systems or human studies of HF progression that are used to develop and test novel diagnostic and therapeutic strategies.
  • In new strategies to prevent HF progression, consider both blockade of pathologic pathways and the preservation or activation of protective pathways lost during the transition from non-pathologic to pathologic states (e.g., the angiogenic response to pressure loads on the heart).
  • Encourage translational studies through the use of novel funding mechanisms, pooled translational infrastructure, and a discovery translational network.

HF Prevention – Critical Gaps in Clinical Research

  • Enrich study populations with the highest risk patients to create feasible and efficient studies that address the potential hurdles of low event rates and small treatment effects in prevention trials. Strong representation of older subjects, women, and minorities is critical, given the heavy burden of disease in these groups and their historical under-representation in clinical trials.
  • Pursue studies to refine and enhance current clinical risk prediction tools to identify the highest risk patients. Future studies should evaluate potential clinical, biomarker, and simplified imaging criteria such as left ventricular (LV) dimension, LV wall thickness, and left atrial size. These criteria could be used in a combined or staged approach to accurately and cost-effectively identify target patient populations.
  • Evaluate multi-technique strategies to identify people from the general community at the greatest long-term risk for developing structural heart disease. Identify which of these patients are likely to progress to symptomatic clinical systolic and diastolic HF, and which unique factors contribute to the development of each form of HF.
  • Develop screening strategies using standard methods, such as screening within established health care provider systems, or novel approaches, such as screening in public venues or using web-based systems.
  • Conduct studies using currently available interventions that might prevent progression to symptomatic HF, as well as novel pharmacological and behavioral interventions. Investigate approaches to increase adherence to therapies proven to prevent or treat the types of cardiovascular disease known to predispose to HF. Aldosterone antagonists, nitric oxide enhancement, exercise, and salt restriction were considered the most promising interventions to evaluate for prevention studies because of the scientific foundation and equipoise about their use in high-risk asymptomatic patients.
  • Evaluate innovative strategies, such as text messages, e-mail, and other electronic technologies, to improve adherence to current guideline-based therapies, as well as novel pharmacological and non-pharmacological interventions. Adherence studies could be conducted independently or within trials testing existing or novel therapies.
  • Conduct adherence/implementation research using existing structures within health care systems such as electronic health records and performance feedback reports.
  • Design clinical trials using clinical endpoints such as all cause mortality and cardiovascular events such as HF hospitalizations, onset of HF, cardiovascular deaths, and other major adverse cardiac events (MACE) to assess the efficacy and effectiveness of potential interventions.
  • Streamline conduct of HF prevention trials by considering the use of centralized institutional boards and data collection, and patient-reported, electronic health record, or CMS database-gathered outcomes.
  • Consider unique data collection methods such as patient transmitted data and working with allied health personnel. Consider alternative venues to identify patients such as pharmacies and health organizations, and alternative screening methods to identify high-risk patients such hand-held echocardiograms.
  • Consider novel approaches to enroll patients into studies such as using standard mail, e-mails, or the internet for low-risk interventions. Leverage integrated health systems, electronic health records, or CMS databases to identify Stage B HF patients. Consider novel strategies to deliver and follow up on interventions, such as web-based platforms, smart phones, or videoconferencing.

Publication Plans

A report is planned for publication in a peer-reviewed journal.

NHLBI Contacts

Monica R. Shah, MD, MHS, MSJ
Division of Cardiovascular Sciences

Nakela L. Cook, MD, MPH
Division of Cardiovascular Sciences

Bishow B. Adhikari, PhD
Division of Cardiovascular Sciences

Working Group Members


  • Marvin Konstam, MD, Tufts Medical Center and Tufts University School of Medicine
  • Margaret Redfield, MD, The Mayo Clinic


  • Lawrence Appel, MD, MPH, Johns Hopkins Medical Institutions
  • Alain Bertoni, MD, MPH, Wake Forest School of Medicine
  • John Burnett, MD, Mayo School of Graduate Medical Education
  • Jay Cohn, MD, University of Minnesota
  • G. Michael Felker, MD, MHS, Duke University School of Medicine
  • Gregg Fonarow, MD, University of California, Los Angeles
  • Thomas Force, MD, Thomas Jefferson University
  • Christopher Granger, MD, Duke University School of Medicine
  • Gerardo Heiss, MD, PhD, University of North Carolina at Chapel Hill
  • Walter Koch, PhD, Thomas Jefferson University
  • Daniel Levy, MD, National Heart Lung and Blood Institute
  • Douglas Mann, MD, Washington University in St. Louis School of Medicine
  • Barry Massie, MD, San Francisco VA Hospital
  • Ileana Pina, MD, Albert Einstein School of Medicine/Montefiore
  • Vasan Ramachandran, MD, Boston University School of Medicine
  • Michael Rich, MD, Washington University in St. Louis School of Medicine
  • Frank Spinale, MD, PhD, Medical University of South Carolina
  • Norman Stockbridge, MD, Food and Drug Administration
  • James Udelson, MD, Tufts University School of Medicine
  • Matthew Weir, MD, University of Medicine School of Medicine

Last Updated: November 2011

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