Food and Pharma: Linking 2 Silos of Heart Failure Research and Therapy∗
A man in cardiac failure is a hero. We meet him every day in the hospital, and we owe it to him to understand him better.—Peter Harris, 1983 (1)
The author of the first comprehensive monograph on cardiovascular diseases published in the United States, Arthur D. Hirschfelder, Johns Hopkins’ first full-time cardiologist, devoted 2 pages to diet in the treatment of “failure of the heart.” His recommendations included limiting fluid intake to 1500 ml a day, and that “salt should also be withheld from the food as far as possible,” based on cited evidence published in 1903 to 1906 (2). Heart failure in 1910 was mostly due to rheumatic valvular disease and syphilitic aortitis with aortic regurgitation. Much of heart failure today is concentrated at the intersection of poor diet quality with diabetes, renal disease, hypertension, and coronary heart disease (3,4). Although primary and secondary prevention of atherosclerotic vascular disease has included focus on dietary intake, there has been relatively little attention to diet and heart failure other than to recommend sodium restriction.
A consensus statement from 2019 on nutrition, obesity, and cachexia in patients with heart failure, focused on dietary quality, micronutrient supplementation, management of obesity, and management of cardiac cachexia, had no discussion of guideline-directed pharmacologic treatment of heart failure (5). Conversely, in the 2021 American College of Cardiology expert consensus decision pathway for optimization of heart failure treatment, roughly 5 words are devoted to diet and exercise; there is no mention of nutrition assessment by a dietician (6). A recent meta-analysis concluded that poor nutrition in patients with heart failure is associated with poor outcomes (7). A current Cochrane review of nutrition support for hospitalized adults at nutritional risk is less sanguine: they report little identifiable benefit of enhanced nutrition in these patients (8). As noted in a seminal paper from the National Institutes of Health, published in 2006, “management of weight loss and cardiac cachexia [in heart failure] is still a conundrum without adequate dietary approaches” (9).
In this issue of the Journal, Hersberger et al. (10) present a prespecified secondary analysis of outcomes in patients with heart failure, from the EFFORT (Effect of early nutritional support on Frailty, Functional Outcomes and Recovery of malnourished medical inpatients Trial) (11). Eight hospitals in Switzerland participated in this study.
Enrollment was based on the Nutritional Risk Screening 2002 (NRS) tool (12). The NRS has 2 components: screening for nutritional risk (weight loss, body mass index [BMI], food intake as percent of normal) and severity of disease (roughly proportional to stress metabolism), ranging from 0 (normal nutritional requirements) to mild, moderate, and severe. One point is added for age ≥70 years.
Most of the subjects in this analysis were age >70 years and were enrolled based on an NRS score ≥3. A typical patient with a score of 3 would be age >70 years, with mild weight loss or reduced food intake in the preceding week (before hospital admission), and have heart failure and other chronic illness such as chronic obstructive pulmonary disease or diabetes. An NRS score of 4 implies weight loss >5% in 2 months or BMI 18.5 to 20.5 kg/m2 and impaired general condition or food intake 25% to 50% of normal, plus severe illness such as stroke, major abdominal surgery, severe pneumonia, leukemia, plus age ≥70 years. The comorbid problems were typical: approximately one-third had diabetes, one-half had hypertension, and approximately one-third had coronary heart disease.
Patients were randomized 1:1 to receive usual Swiss Hospital food, or to receive a nutritional assessment by a dietician, to reach protein and energy goals of 1.2 to 1.5 g/kg body weight with target of 0.8 g/kg body weight for patients with acute renal failure. Average glomerular filtration rate for the group was approximately 40 ml/min/1.73 m2, or chronic kidney disease stage 3b. Nutritional support was provided by fortification with protein powder or, if oral feeding was not sufficient, in approximately 5% of subjects, enteral tube feeding, or parenteral feeding. There was no salt restriction; fluid restriction was individualized.
The primary outcome was all-cause mortality 30 days after randomization. Secondary endpoints were major cardiovascular events (MACE), length of index hospital stay, functional impairment in activities of daily living, quality of life, and 6-month mortality. Roughly one-third of the subjects were admitted to hospital with acute decompensated heart failure and two-thirds had chronic heart failure with other admitting diagnoses. Compared with subjects with NRS 3 to 4, those with NRS >4 had a highly significant 65% increased mortality risk over 180 days. The component of the NRS with the strongest association with mortality was low food intake in the preceding week.
The intervention group had more energy and protein intake; at hospital discharge, 25.2% of the intervention group received oral nutrition support as compared with only 0.9% of the control group. Thirty-day mortality in the intervention group was 8.4% compared with 14.8% of the control. The benefit, when stratified by nutritional risk, was seen only in the subjects with NRS >4 points. The mortality effect was still significant at 180 days.
The EFFORT study enrolled moderately to severely ill, mostly geriatric, hospitalized patients. The beneficial effect of nutritional enrichment in the overall study population was seen in the patients with NRS of 5 or more: very sick patients. The design of the study precludes determining if the mortality improvement was due to nutritional support or to the input from the dietician and other support staff in this unblinded study. There are no data on the presence of physical findings associated with heart failure. The standard biomarker of N-terminal pro–B-type natriuretic peptide was available on less than one-half of the study population, so the severity of the heart failure cannot be determined. The subset analysis by etiology of heart failure suggests that most of the benefit of nutritional enhancement was seen in male patients age >78 with acute-onset heart failure with reduced ejection fraction, and moderate nutritional risk. Differences in outcomes with regard to MACE were mainly in men older than 78.
This study adds another tile to the still-fragmentary mosaic picture of the patient with heart failure at nutritional risk who might benefit by additional nutritional support. “Good medical care” dictates that all hospitalized patients deserve to have a standardized nutritional assessment; the challenge remains: how to determine which patient with heart failure at nutritional risk will benefit by medical nutrition therapy.
In summary, in this randomized trial of protocolized nutritional support in patients with heart failure, the patients who appeared to benefit most were men older than 78 years with systolic heart failure and other acute and chronic medical illnesses. Improving personalized nutritional support for patients suffering from heart failure will require teamwork between members of both “silos” of the heart failure research community. To reprise Dr. Harris: “The patient with heart failure is a hero; we see him every day in the hospital; he deserves to have us understand him better” (1).
Funding Support and Author Disclosures
Dr. Gottlieb owns a Federal trademark for “Greens, Beans, and Leans” diet, and has a pending Federal trademark for “FLOATS”: flax + oats cereal.
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