Heart Failure

HF: Energy Needs (2007)


Toth MJ, Gottlieb SS, Goran MI, Fisher ML, Poehlman ET. Daily energy expenditure in free-living heart failure patients. Am J Physiol. 1997; 272 (Endocrinol Metab. 35): E469-E475.

Study Design:
Cross-Sectional Study
D - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
To determine if daily energy expenditure is elevated in heart failure patients.
Inclusion Criteria:
  • Heart failure with cachexia as determined by a 10% or greater weight loss since pre-morbid state or without cachexia
  • Controls who had no signs or symptoms of heart disease or diabetes, normal resting electrocardiogram and after an exercise stress test, absence of drugs that could affect cardiovascular or metabolic function and stable weight for six months.
Exclusion Criteria:

Cigarette use within the previous three months.

Description of Study Protocol:


  • Patients at the Heart Failure Service of the Baltimore Veterans Administration Medical Center and the University of Maryland Medical Center
  • Normal controls were recruited by newspaper advertisements and community organizations in Baltimore, MD, and surrounding areas (African-Americans) and Burlington, VT, and surround areas (Caucasians). 



Statistical Analysis

  • Differences in physical and metabolic characteristics among groups were assessed by a one-way analysis of variance. If a significant group effect was found, a Student-Newman-Keuls test was used to identify the location of differences among groups.
  • Differences in clinical characteristics between the two groups of heart failure patients were determined using an unpaired Student's T-test
  • Analysis of covariance was used to test for differences in peak VO2 and resting energy expenditure after the effects of fat-free mass had been statistically removed
  • Because tumor necrosis factor-A data were not normally distributed, differences in tumor necrosis factor-A were determined by Mann-Whitney U-test
  • The relationship between tumor necrosis factor-A and body composition, energy expenditure and energy intake data was determined by Spearman's rank correlation analysis
  • Significance level was set at P<0.05
  • All values are expressed as means ±SD.
Data Collection Summary:

Timing of Measurements

All measurements were made over a 10-day period.

  • Day One: Subjects received an oral dose of doubly-labled water after a baseline urine sample
  • Day Two: Resting energy expenditure and body composition were measured and two urine samples were collected to mark the beginning of the doubly-labeled water measurement period. A scale and instructions were given for recording dietary intake. 10 days after the beginning of the doubly-labeled water meaurement period, subjects provided two urine samples and underwent an assessment of peak oxygen consumption (VO2).

Dependent Variables

  • Variable One
    • Daily energy expenditure was determined using the doubly-labeled water technique
    • Each subject consumed a mixed oral dose of 2H2O and H218O (0.078g and 0.092g per kg body mass, respectively) after providing a baseline urine sample (between the hours of 12:00 p.m. and 4:00 p.m.)
    • A weighed 1:400 dilution (dose:tap water) was prepared from each subject's dose and a sample of the water used for the dilution was saved and analyzed with each subject's sample set
    • Two urine samples were obtained the morning after dosing to mark the beginning of the measurement period and 10 days later to mark the end (all between 8:00 a.m. and 12:00 p.m.)
    • All subjects were weight-stable and consumed a self-selected diet during the doubly-labeled water measurement period
    • Urine samples were stored in sealed vacutainers at -20ºC until analysis in triplicate by isotope ratio mass spectrometry
    • Samples were analyzed for isotopic enrichment of H218O, using the off-line zinc reduction procedure of Kendall and Copelan and the CO2 equilibration technique, respectively
    • The 2H and 18O enrichment of samples was expressed on the relative delta per mil scale.
  • Variable Two
    • Resting energy expenditure was measured in the morning (approximately 8:00 a.m.) after a 12-hour overnight fast
    • Resting metabolic rate was measured by indirect calorimetry, using the ventilated hood method for 45 minutes (Deltratrac)
    • Heart failure patients were transported to the testing area by wheelchair and allowed to rest quietly in a dark room for 20 minutes before measurement to ensure resting conditions
    • Energy expenditure was caculated using the equation of Weir
    • All subjects were asked to refrain from any exercise or heavy exertion the day before measurement. 
  • Variable Three: Physical activity energy expenditure was calculated on the basis of the three-component model of daily energy expenditure. It was calculated [(0.9 x daily energy expediture) - resting energy expenditure], with the assumption that the thermic effect of food constitutes 10% of daily energy expenditure in older individuals.  
  • Variable Four: Body composition
    • Fat mass and fat-free mass were meaured by dual-energy X-ray absorptiometry (Lunar DPX-L densitometer)
    • All scans were analyzed with the use of the Lunar version extended analysis program for body composition
    • The hydration fraction of fat-free mass was calculated by dividing total body water (measured with isotope dilution) by fat-free mass (measured with dual-energy X-ray absorptiometry). 
  • Variable Five
    • Human tumor necrosis factor-A was measured from plasma samples by sandwich enzyme-linked immunosorbent assay
    • All samples were analyzed in the same assay. 
  • Variable Six: Peak VO2 was assessed by a treadmill test to volitional exhaustion using an open-circuit indirect caloimetry system
  • Variable Seven
    • Dietary intake was measured for three days (one weekend and two week days) during the doubly-labeled water period
    • Each subject was supplied with a five-pound metabolic scale and instructed on the accurate measurement and recording of intake
    • Subjects were strongly encouraged not to change their dietary habits during the recording period
    • Food records were analyzed using the Nutritionist 4.1 program
    • Food quotient (FQ) was calculated using the equation FQ=[(1.00 x carbohydrate percentage)+(0.81 x protein percentage)+(0.72 x fat percentage) + (0.67 x alcohol percentage)]/100, where each nutrient is expressed as the percentage of the total kilocalories consumed.

Control Variables

Heart failure with and without cachexia vs. healthy individuals.

Description of Actual Data Sample:

Initial N

  • 25 with heart failure (24 male, one female; 52% Caucasian, 48% African-American)
  • 12 (11 male, one female; 42% Caucasian, 58% African-American) were cachectic
  • 13 were non-cachectic (13 male; 62% Caucasian, 38% African-American)
  • 50 controls (48 men, two female; 60% Caucasian, 40% African-American). 

Attrition (Final N)

All completed the study, except that peak VO2 was available for 16 heart failure patients.


  • Cachectic: 73±6
  • Non-cachectic: 67±5
  • Controls: 69±6.


Caucasian and African-American described above.


  • Cachectic patients were statisically significantly older (P≤0.05), weighed less (P≤0.05) and had a smaller BMI (P≤0.05), fat mass and fat-free mass (both P≤0.05)
  • Mean left ventricular ejection fraction was 23±9% (range 10-45%)
  • Heart failure patients were taking two or more of the following medications: Diuretics (N=25), vasodilators (N=21), digoxin (N=23).


Baltimore, MD and Burlington, VT, (healthy Caucasians) and their surrounding areas.

Summary of Results:


Cachectic Patients
(Measures and Confidence Intervals)

Non-Cachectic Patients
(Measures and Confidence Intervals)

Control Group
(Measures and Confidence Intervals)

Statistical Significance of Group Difference

Daily Energy Expenditure





Physical Activity Expenditure










REE (Adjusted FFM) 1,559±182 1,639±173* 1,542±169 *P≤0.09
Reported Energy Intake 1,987±529 1,836±509 2,125±576 NS
Fat Mass (kg) 12±9* 25±11 21±8  *P≤0.05
Fat-Free Mass 50±8* 59±5 58±9 *P≤0.05

Other Findings

  • Tumor necrosis factor-A levels were not different between the cachectic and non-cachectic patients
  • Adjusted Peak VO2 for eight each of the heart failure groups was not significantly different.
Author Conclusion:
  • This study did not find an elevated energy expenditure in cachectic patients. Cachetic patients had a lower daily energy expenditure, compared with non-cachectic patients and controls.
  • Differences in energy expenditure among groups were primarily due to differences in physical activity. Another contributing factor in cachetic patients was their lower REE.
  • Authors suggest that reduced energy intake accounts for the weight loss in heart failure patients. Thus, authors conclude that inadequate energy intake, not elevated energy expenditure, accounts for the weight loss in heart failure patients.
Funding Source:
Reviewer Comments:

Poehlman ET was charged with falsifying data on some of his studies. The Office of Research Integrity listed the studies that were affected by this misconduct. This paper was not one of those, therefore it is being considered and reviewed.

Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? No
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? No
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? N/A
  4.1. Were follow-up methods described and the same for all groups? N/A
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? N/A
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) No
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? No
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? Yes
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? N/A
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? N/A
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? No
  8.6. Was clinical significance as well as statistical significance reported? No
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes