The Goldilocks Dilemma in Pediatric Heart Disease: Neither Too Big Nor Too Small

Conceptual Model: Body Mass Index and Outcomes

Obesity (defined in children and adolescents as a body mass index [BMI] >95% for age and sex) is both prevalent in the general population and associated with increased lifetime risk for morbidity and mortality.1-3 The National Health And Nutrition Examination Survey (NHANES) demonstrated that 30% of American children are overweight or obese.4,5 Single-center cross-sectional studies have demonstrated that the prevalence of obesity is similar in children with CHD to those seen in cardiac-normal populations.6,7 However, the effect of body mass/composition on outcomes following surgery for acquired and congenital heart disease (CHD) in young patients has not been studied until very recently.

Conventional wisdom held that obesity was associated with increased risk of perioperative adverse outcomes because of co-morbid medical co-morbidities (e.g., diabetes, hypertension, and peripheral vascular disease), increased technical complexity due to body habitus and increased risks of wound infection and/or dehiscence. Studies of adults undergoing cardiac surgery, however, have consistently demonstrated an "obesity paradox," in which overweight and moderately obese states are associated with the lowest risk of following surgery. Normal weight and extremely obese states are associated with intermediate risk, and the highest risks are associated with underweight states.8-12

While obesity has received significant attention, underweight (BMI <5% for age and sex) status has been less well studied. Several studies have demonstrated increased risk of mortality after cardiac surgery in elderly cardiac patients.8-12 Underweight and/or unplanned weight loss are associated with increased longer-term mortality in elderly heart failure patients.13-15 This underscores the importance of considering both extremes of BMI in studies evaluating the association of body composition and outcomes.

The association between underweight and adverse outcome may be due to multiple factors. In the elderly, this association has been attributed to heart failure associated cachexia syndrome, in which a cascade of inflammatory processes results in not only unplanned weight loss but also immune dysfunction and impaired wound healing. In addition, in pediatric cardiac patients, underweight status may be an indicator of a genetic syndrome or other chronic non-cardiac conditions.

Observational Studies in Pediatric Cardiac Patients

Though it is tempting to extrapolate data from the aforementioned studies in elderly adults and apply their conclusions to young patients undergoing cardiac surgery, there are several reasons to exercise caution before doing so. The "time of exposure" to their specific BMI in elderly patients is simply longer. Furthermore, obesity is more clearly part of the causal pathway in atherosclerotic heart disease and ischemic cardiomyopathy.

Until recently there was limited data about the association between BMI and outcomes following cardiac surgery. A single-center retrospective cohort study demonstrated that underweight transplant recipients were at higher risk of graft failure when compared to normal weight and obese subjects.16 More recently, a multi-center retrospective matched cohort study using data from the Pediatric Health Information Systems database studied the association of obesity and perioperative outcome. The study was limited by low statistical power, difficulty in ascertaining body mass status using International Classification of Disease codes and the inability to identify underweight subjects. No difference was seen between obese and non-obese subjects in operative mortality, though obesity was associated with a higher cost of hospitalization.17

A multicenter retrospective cohort study used data from the Society For Thoracic Surgeons Congenital Heart Surgeons Database, which includes the majority of North American surgical programs, has advantages in terms of sample size, data regarding clinically relevant outcomes and a validated empirical risk-adjustment model.18 This study demonstrated that in young patients between 8 and 25, 16% of subjects were either underweight or severely underweight and 16% were obese.

Both extremes of BMI were associated with increased risk of a composite outcome (death, major adverse event, and prolonged length of stay) even after adjustment for case-mix (Figure 2).19 The odds ratio for severely underweight subjects was 1.53 (95% confidence interval: 1.31-1.79) while for obese subjects it was 1.21 (95% confidence interval: 1.05-1.39). The study was underpowered to detect a difference in odds of mortality, which was thankfully rare, but data suggested that mortality might also be increased in either extreme of BMI.

Future Directions

Observational studies are important means in identifying pertinent associations and generating hypotheses, but there are still significant knowledge gaps. BMI is used broadly as a measure of body composition, though it may not be the most sensitive and specific marker of risk. It is also possible that what is considered a "normal" BMI for most children is not true in those with cardiac disease, as some forms of heart disease may also be associated with bony, soft tissue and musculoskeletal abnormalities.20,21 Currently, however, the convenience and predictive value of BMI make it the "best available" measure of body composition clinically and in observational studies.

From a practical standpoint it is unclear how (or even if it is at all possible) to safely modify BMI at either end of the spectrum. More research is necessary to determine whether short-term changes in BMI (in either direction) will be accompanied by commensurate improvement in outcomes. Experimental or quasi-experimental study designs are necessary to address these questions. It is also important to acknowledge that the mechanism underlying the observed associations is not clear, and that a more complete understanding has the potential to identify maximally effective means of improving patient outcomes. In the meantime, awareness of these issues should inform decision making where possible.

References

  1. Flegal KM, Graubard BI, Williamson DF, Gail MH. Cause-specific excess deaths associated with underweight, overweight, and obesity. JAMA 2007;298:2028-37.
  2. Flegal KM, Graubard BI, Williamson DF, Gail MH. Excess deaths associated with underweight, overweight, and obesity. JAMA 2005;293:1861-7.
  3. Berrington de Gonzalez A, Hartge P, Cerhan JR, et al. Body-mass index and mortality among 1.46 million white adults. N Engl J Med 2010;363:2211-9.
  4. Ogden CL, Carroll MD, Flegal KM. High body mass index for age among US children and adolescents, 2003-2006. JAMA 2008;299:2401-5.
  5. Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002. JAMA 2004;291:2847-50.
  6. Pinto NM, Marino BS, Wernovsky G, et al. Obesity is a common comorbidity in children with congenital and acquired heart disease. Pediatrics 2007;120:e1157-64.
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  8. Mariscalco G, Wozniak MJ, Dawson AG, et al. Body mass index and mortality among adults undergoing cardiac surgery: a nationwide study with a systematic review and meta-analysis. Circulation 2017;135:850-63.
  9. Valentijn TM, Galal W, Tjeertes EK, Hoeks SE, Verhagen HJ, Stolker RJ. The obesity paradox in the surgical population. Surgeon 2013;11:169-76.
  10. Birkmeyer NJ, Charlesworth DC, Hernandez F, et al. Obesity and risk of adverse outcomes associated with coronary artery bypass syndrome. Northern New England Cardiovascular Disease Study Group. Circulation 1998;97:1689-94.
  11. Prabhakar G, Haan CK, Peterson ED, Coombs LP, Cruzzavala JL, Murray GF. The risks of moderate and extreme obesity for coronary artery bypass grafting outcomes: a study from the Society of Thoracic Surgeons' database. Ann Thorac Surgi 2002;74:1125-30.
  12. Reeves BC, Ascione R, Chamberlain MH, Angelini GD. Effect of body mass index on early outcomes in patients undergoing coronary artery bypass surgery. J Am Coll Cardiol 2003;42:668-76.
  13. Pocock SJ, McMurray JJ, Dobson J, et al. Weight loss and mortality risk in patients with chronic heart failure in the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) programme. Eur Heart J 2008;29:2641-50.
  14. Rossignol P, Masson S, Barlera S, et al. Loss in body weight is an independent prognostic factor for mortality in chronic heart failure: insights from the GISSI-HF and Val-HeFT trials. Eur J Heart Fail 2015;17:424-33.
  15. Anker SD, Ponikowski P, Varney S, et al. Wasting as independent risk factor for mortality in chronic heart failure. Lancet 1997;349:1050-3.
  16. Rossano JW, Grenier MA, Dreyer WJ, et al. Effect of body mass index on outcome in pediatric heart transplant patients. J Heart Lung Transplant 2007;26:718-23.
  17. Shamszad P, Rossano JW, Marino BS, Lowry AW, Knudson JD. Obesity and diabetes mellitus adversely affect outcomes after cardiac surgery in children's hospitals. Congenit Heart Dis 2016;11:409-14.
  18. O'Brien SM, Clarke DR, Jacobs JP, et al. An empirically based tool for analyzing mortality associated with congenital heart surgery. J Thorac Cardiovasc Surg 2009;138:1139-53.
  19. O'Byrne ML, Kim S, Hornik CP, et al. Effect of obesity and underweight status on perioperative outcomes of congenital heart operations in children, adolescents, and young adults: an analysis of data from the Society of Thoracic Surgeons Database. Circulation 2017;136:704-18.
  20. Avitabile CM, Goldberg DJ, Zemel BS, et al. Deficits in bone density and structure in children and young adults following Fontan palliation. Bone 2015;77:12-6.
  21. Avitabile CM, Leonard MB, Zemel BS, et al. Lean mass deficits, vitamin D status and exercise capacity in children and young adults after Fontan palliation. Heart 2014;100:1702-7.

Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Congenital Heart Disease, CHD and Pediatrics and Prevention, CHD and Pediatrics and Quality Improvement, Acute Heart Failure, Hypertension

Keywords: Heart Defects, Congenital, Pediatrics, Body Mass Index, Nutrition Surveys, Weight Loss, Risk Adjustment, Cross-Sectional Studies, International Classification of Diseases, Health Information Systems, Retrospective Studies, Overweight, Body Weight, Coronary Artery Disease, Heart Failure, Diabetes Mellitus, Body Composition, Diagnosis-Related Groups, Hypertension, Decision Making, Peripheral Vascular Diseases, Cardiomyopathies, Musculoskeletal Abnormalities


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