NHLBI Working Group

Designing Clinical Studies to Evaluate the Role of Nutrition and Diet in Heart Failure Management

June 6-7, 2013


Executive Summary

Agenda word document (30KB)


Purpose

The National Heart, Lung, and Blood Institute (NHLBI) and NIH Office of Dietary Supplements (ODS) convened a working group on June 6 and 7, 2013. Members were asked to: 1) assess the evidence base for dietary and nutritional guidance for heart failure (HF) patients; 2) identify critical evidence gaps regarding the efficacy and clinical utility of dietary interventions for meeting nutritional needs, mitigating symptoms, and potentially arresting or reversing HF progression; and 3) consider how to develop new knowledge in the field and approaches for translation that will optimally use existing or new evidence, including novel study designs and methodological approaches. An important aspect of this working group was the dialogue among experts representing cardiology, nephrology, nutrition science, biostatistics and clinical trials, and basic science. In addition to NHLBI and ODS, representatives from NIDDK, NIA, and NINR participated. These stakeholders considered needs, opportunities, and obstacles regarding medical nutrition therapy (MNT) and HF management. The working group is responsive to NHLBI Strategic Plan Goals 1, 2, and 3. Recent meta-analyses, including an IOM report entitled Sodium Intake in Populations: Assessment of Evidence, conclude that current nutrition guidelines recommending sodium restriction, the most commonly prescribed dietary modification in HF, are poorly evidenced and may cause harm, adding urgency to the deliberations and recommendations from the working group.

HF remains a major public health burden. However, compared with the situation for cardiovascular risk factor management, there is little well-founded evidence regarding the efficacy, safety, and clinical impact of dietary modifications for patients with various HF phenotypes. The importance of diet and nutrition to promote health and prevent or control disease is well established. The obesity epidemic has fueled keen interest and focused investigations to develop nutritional guidelines to prevent cardiovascular disease, especially hypertension, metabolic syndrome, and atherosclerosis in the general population. In contrast, assessment tools and determining nutritional needs for the patient with HF lack high caliber evidence regarding safety, efficacy, and clinical impact of dietary modifications. The stronger evidence and focus on disease prevention and health promotion with diet modifications like DASH cannot be easily applied or extrapolated for disease management, especially HF, because of critical knowledge gaps and potential harm.

Chronic HF often presents as a multisystem disease with important co-morbidities such as anemia, insulin resistance or diabetes, autonomic dysregulation, and impaired renal function. Intestinal dysfunction with impaired motility and circulation and disturbed intestinal barrier and flora may lead to a chronic inflammatory state and nutrient malabsorption. In advanced cases, catabolic/anabolic imbalance is associated with cardiac cachexia, a difficult to treat condition which itself carries a poor prognosis. Finally, psychosocial symptoms associated with HF, such as depression and impaired cognition, can result in poor self-care, which can include lack of adherence to recommended dietary, physical activity, and medication regimens. Nutritional status concerns for patients with HF increase with disease severity. Nevertheless, except for salt restriction, which has become controversial, clinicians give little attention to diet as a potential intervention to improve outcomes, both for lack of evidence on efficacy and lack of conviction that adherence will be adequate.

The following themes emerged from discussion. Optimal management in HF must include nutrition therapy based on sound evidence. The need for research to establish evidence for nutritional guidance is compelling and immediate. Given the enormous public heath burden and high health care utilization and costs of HF on one hand and the potential for improved outcomes with dietary modification on the other, there is a strong consensus calling for commitment from the research community to resolve evidence gaps for nutrition therapy in HF now. Needs and opportunities for fundamental and clinical studies to address a number of novel promising strategies and to elucidate mechanisms of protein wasting which if answered would increase impact of diet modification were also identified. NHLBI, other institutes and partners with shared interest should consider trans-NIH approaches to enhance nutrition research leveraging existing resources. Strategies to promote multicenter, investigator initiated studies are also needed

Recommendations

There remains uncertainty regarding the role of sodium, fluid, nutrients, and catabolism in the natural history of HF and the potential of nutritional interventions, whether through food or supplements, to improve clinical and quality-of-life outcomes. To determine optimal HF therapy and to introduce non-pharmacologic treatments that may favorably improve the natural history of HF, reducing both the health burden and economic consequences of this disease, the following recommendations are proposed:

  1. Determine the correct sodium threshold.
    • The top tier research questions focus on appropriate ranges of sodium and fluid intake, and the safety thereof, for various HF patient sub-groups including HFPEF, HFREF, and cardiorenal syndrome.
  2. Generate new knowledge which identifies therapeutic targets.
    • In HF, basic and fundamental scientific investigations are needed to elucidate the effects of sodium, fluid, and caloric intake on metabolic homeostasis (including weight loss under various conditions), cardiac structure, function, arrhythmia burden, gut microbiome, morbidity such as HF readmission, and mortality and should be given high priority.
    • Understand the role of the gut microbiome on gastrointestinal malabsorption, inflammation, and protein balance in HF.
    • Elucidate the effect of MNT therapy on muscle mass in HF and better understand both the genesis and the treatment of sarcopenic obesity.
  3. Apply innovative study designs to reduce evidence gaps.
    • A clear imperative is to design large adequately powered efficacy studies (e.g., randomized clinical trials and/or registries) to address critical evidence gaps such as sodium and fluid restriction in HF. Important ancillary and mechanistic sub-studies which may change dietary practice and guidelines would be enabled by the conduct of large simple efficacy projects.
    • Adaptive trial designs and group randomized MNT for trials may be uniquely applicable to some of the questions being posed.
    • Complex study design issues and high costs present unique problems for clinical investigations in nutrition. Research questions could be addressed through studies conducted in an array of research, practice, and residential settings, including at home with care by self, family, or other providers; practice settings such as managed care or other office arrangements; and residential settings (assisted living, nursing homes, etc); and in-hospital (acutely decompensated patients newly admitted or being prepared for discharge) and post-discharge. Interventions could vary among controlled diets, self-selected diets, institutional diets, etc. Data gathering could be through well-established methods, through new electronic health record-based approaches, and other methods.
    • Novel factorial designs that address protein and calorie augmentation, weight and body composition management, micronutrients and/or dietary supplements should be strongly considered.
  4. Develop technologies to facilitate nutrition research.
    • Relevant animal models of heart failure, as well as genomics, metabolomics, and small molecule technologies, should be applied to gain understanding of the human mechanisms of disease and response to nutrient intervention.

Working Group Members

Co-Chairs
Frank Sacks, MD - Harvard School of Public Health
Clyde Yancy, MD - Northwestern University

Working Group Speakers
Larry Appel, MD - Johns Hopkins University
Javed Butler, MD, MPH - Emory University
Luc Djousse, MD, ScD - Harvard Medical School
Lorraine Evangelista, PhD, RN - University of California - Irvine
Gregg Fonarow, MD - University of California - Los Angeles
Alan Go, MD - Kaiser Permanente
Scott Hummel, MD - University of Michigan
T. Alp Ikizler, MD - Vanderbilt University
Terry Lennie, PhD, RN - University of Kentucky
Dariush Mozaffarian, MD, DrPH - Harvard Medical School
Michael Rich, MD - Washington University St. Louis
Linda Van Horn, PhD, RD - Northwestern University
Janet Wittes, PhD - Statistics Collaborative

Invited Working Group Discussants and Observers
Kevin Davy, PhD - Virginia Polytechnic Institute
Katherine Dennison, RD, MPH - Washington VA Hospital Center
Sheldon Gottlieb, MD - Johns Hopkins University
Jerry Gurwitz, MD - University of Massachusetts
Paul Hauptman, MD - St. Louis University
Stephen Houser, PhD - University of Pennsylvania
Eldrin Lewis, MD, MPH - Harvard Medical School
Hilda Maibach, MS - Social and Scientific Systems
Ann Nothwehr, MA, RD, LD, CNSC - Shady Grove Adventist Hospital
Paul Poirier, MD, PhD - Quebec Heart Institute
Dorothea Vafiadis, MPH - American Heart Association
Edward Weiss, PhD - St. Louis University

NIH Staff

Project Officers
Abby Ershow, ScD - Division of Cardiovascular Sciences - NHLBI
Patrice Desvigne-Nickens, MD - Division of Cardiovascular Sciences - NHLBI
Becky Costello, PhD - Office of Dietary Supplements - OD/NIH

Planning Committee
Lawton Cooper, MD, MPH - Division of Cardiovascular Sciences - NHLBI
Susan Czajkowski, PhD - Division of Cardiovascular Sciences - NHLBI
Simhan Danthi, PhD - Division of Cardiovascular Sciences - NHLBI
Cindy Davis, PhD - Office of Dietary Supplements - OD/NIH
Judy Hannah, PhD - Division of Geriatrics and Clinical Gerontology - NIA
Karen Huss, DNSc, RN, APRN-BC - Division of Extramural Activities - NINR
Camille Jackson - Division of Cardiovascular Sciences - NHLBI
Janet de Jesus, MS, RD - Division of Cardiovascular Sciences - NHLBI
Juliana Keleti, PhD - Division of Cardiovascular Sciences - NHLBI
Paul Kimmel, MD - Division of Kidney, Urologic, and Hematologic Diseases -- NIDDK
Eric Leifer, PhD - Division of Cardiovascular Sciences - NHLBI
Kathryn McMurry, MS - Division of Cardiovascular Sciences - NHLBI
Hanyu Ni, PhD - Division of Cardiovascular Sciences - NHLBI
Charlotte Pratt, PhD, RD - Division of Cardiovascular Sciences - NHLBI
Christopher Sempos, PhD - Office of Dietary Supplements - OD/NIH
Pothur Srinivas, PhD, MPH - Division of Cardiovascular Sciences - NHLBI
Myron Waclawiw, PhD - Division of Cardiovascular Sciences - NHLBI
Jackie Wright, PhD - Division of Cardiovascular Sciences - NHLBI
Susan Zieman, MD, PhD - Division of Geriatrics and Clinical Gerontology - NIA

Last Updated: Aug 2013




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