I Current Review

Malnutrition and the heart

John G. Webb, MD Marla C. Kiess, MD, FRCPC Clifford C. Chan-Yan, MD, FRCPC

Earlier concepts that the heart is spared in tante du point de vue clinique mais qu'on ne have been shown to be incorrect. soupconne pas toujours. Une therapeutique nu- Inadequate intake of protein and energy results tritive est susceptible d'ameliorer certains mala- in proportional loss of skeletal and myocardial des souffrant de cachexie cardiaque qui devront muscle. As myocardial mass decreases, so does subir une intervention de chirurgie cardiaque et the ability to generate cardiac output; however, d'autres qu'une perte rapide de poids expose i la various compensatory factors come into play. mort subite par arythmie. Les malades hospitali- Nutritional supplementation for malnourished sds souffrent souvent de malnutrition; beaucoup patients reverses the compensatory factors and d'entre eux bEnEficient maintenant d'une thdra- may increase the short-term potential for heart peutique nutritive. Ces deux faits ont d'impor- failure. Severe cardiac debility results in poor tantes incidences sur le coeur. nutrition, which may in turn produce unsus- pected but clinically significant myocardial atro- phy. Nutritional support may play a role in he effects of specific nutritional deficiencies improving cardiac function in selected patients of and trace elements on the heart with cardiac who are being prepared are not well understood. Thiamine deficien- for cardiac surgery and in patients with rapid cy produces peripheral vasodilation,1 with resul- who are at risk for sudden death due tant high-output cardiac failure, and certain elec- to . Malnutrition is common in hos- trolyte deficiencies reduce cardiac contractility.2-4 pitalized patients, and many patients in hospital deficiency has been associated with a now receive nutritional supplementation; both common in certain regions of facts have important cardiac implications. China,56 and fatal selenium cardiomyopathy has been reported in patients receiving long-term par- enteral nutrition.7-9 On a cru a tort que le coeur ne souffre pas dans Of more clinical importance, however, is les etats de malnutrition. L'apport insuffisant de "protein-calorie" malnutrition - starvation. Exam- proteines et de calories determine le meme ination of the patient may suggest malnutrition on degre d'atrophie au myocarde et k la musculatu- the basis of decreased body fat and skeletal mus- re de l'appareil locomoteur. La perte de masse cle. Anthropometric assessment, including mea- myocardique diminue le debit cardiaque. Des surement of the triceps skinfold thickness and of phenomenes compensateurs entrent alors en jeu; the arm muscle circumference and calculation of leur renversement par un apport nutritif sup- the weight/height index and the creatinine/height plementaire augmente parfois, k breve echeance, index, is easily performed and permits comparison le risque de defaillance cardiaque. La faiblesse with tables of standard values.10'11 With more cardiaque elle-meme nuit a la nutrition, d'oiu advanced malnutrition, visceral proteins become possibilite d'une atrophie myocardique impor- depleted as well. When the rate of catabolism is increased, as with surgery, sepsis or severe illness, profound deficiencies of visceral proteins may From the Department of Medicine, St. Paul's Hospital and develop before a loss of body fat or skeletal muscle University ofBritish Columbia, Vancouver becomes apparent. Visceral proteins are essential Reprint requests to: Dr. John G. Webb, Division of Cardiology, in wound healing, host defences, maintenance of Toronto Western Hospital, 399 Bathurst St., Toronto, Ont. osmotic pressure and homeostatic enzymatic pro- M5T 2S8 cesses. Deficiencies of this compartment are more

- For prescribing information see page 819 CMAJ, VOL. 135, OCTOBER 1, 1986 753 useful in assessing disorders than are losses of ately. However, because of the decrease in body body fat or skeletal muscle."1 Severe deficiency of size the stroke-volume index and the cardiac index visceral proteins may be suggested by low levels of remain normal or rise slightly.25'27'28 In addition, serum proteins, such as albumin and transferrin,1' systolic ejection phase indices of left ventricular or by anergy on skin testing with common anti- function, such as ejection fraction and mean rate of gens.12"13 shortening of left ventricular circumferential fibres, Anthropometric and laboratory assessments remain normal or increase slightly.27 Therefore, have suggested that 25% to 50% of patients in despite the decrease in muscle mass, the needs of hospital for more than 2 weeks suffer from some the circulation are met by these compensatory degree of protein-calorie malnutrition.14"15 Many mechanisms. disorders are associated with rapid weight loss and In starvation there is a deficiency of protein poor intake or use of nutrients. Protein-calorie substrate for maintenance of muscle protein. Me- malnutrition, although common in patients in hos- tabolism is shifted toward catabolism of muscle pital, often goes unrecognized and can have im- protein for gluconeogenesis and maintenance of portant cardiac implications. the body's other critical protein-requiring func- tions. The decrease in cardiac size is likely both a result of impaired myocardial protein maintenance Protein-calorie malnutrition and an adaptive response to decreased demands. Skeletal, myocardial and visceral proteins can Concepts of the effect of starvation on the be decreased even in obese patients. If a person heart have recently changed. The earliest report of has insufficient protein or energy intake, as with a study, by Voit,'6 in 1866, involved two cats, one intestinal bypass surgery, fasting29 or dieting,2' of which was starved for 13 days. Comparing the protein catabolism may occur to a greater degree hearts, Voit found that the heart of the starved cat than fat catabolism. Thus, obesity does not ensure was only slightly smaller, and he concluded that adequate protein stores, and obese patients may the heart is "spared" in malnutrition. This concept have low levels of serum proteins, diminished was widely accepted until it became evident from skeletal muscle and reduced myocardial mass. large autopsy studies of starved people that the amount of cardiac tissue is usually reduced in proportion to the degree of of the rest Congestive cardiac failure of the body.17 During World War II Keys and colleagues The effect of protein-calorie malnutrition on placed healthy conscientious objectors on a "Euro- the heart may not be well recognized because it so pean famine diet", consisting of small quantities of rarely results in cardiac failure. Various compensa- turnips, potatoes and cereals. After 6 months on tory mechanisms mask the effects of myocardial this low-energy, low-protein diet, the volunteers' atrophy. Notably, blood pressure, heart rate, blood average weight loss was 25%. Radiographs volume and metabolic demands for oxygen deliv- showed that the heart size was markedly de- ery decrease in the malnourished patient.17-20'23'27 creased in all dimensions, the decrease in calculat- Carbohydrate and fat intake have a marked ed cardiac volume being 70% of the decrease in direct effect on the plasma catecholamine lev- total body weight.7",8 els.30'3' The fasting patient is in a hypoadrenergic Since this landmark study a decrease in heart state, and this likely plays a role in the size and myocardial atrophy have been widely commonly found in starved patients.3233 In Keys documented in patients with ,18-20 en- and coworkers' original study the average heart ergy-restricted diets,21 nervosa22 and car- rate declined steadily from 56 to only 35 beats/ diac cachexia.18,23 Pathological studies have shown min at the height of starvation.'8 In addition, atrophy and vacuolization of fibres, catecholamines stimulate the production of renin, with a decrease in size and, on occasion, fragmen- angiotensin and aldosterone. Low levels of cate- tation of myofibrils.24-26 cholamines in starved patients may lead to a fall in Heymsfield and associates27 correlated the de- blood pressure through both vasodilation and crease in heart size observed radiographically with decreased sodium retention.'8'23'32'33 Starvation is a a reduction in myocardial mass demonstrated by natriuretic state; conversely, carbohydrate intake in echocardiography. Comparing a group of malnour- a fasting person rapidly decreases renal sodium ished patients in hospital with height-matched excretion.3436 In addition, a malnourished patient controls, they found by radiography a 37% de- may ingest very little salt. In mild malnutrition the crease in heart volume and by echocardiography a plasma volume per unit weight may rise, but as 22% decrease in left ventricular mass due to malnutrition becomes more severe the plasma myocardial atrophy and a 37% decrease in end- volume often falls.37 The erythrocyte mass is often diastolic volume. The decrease in heart size was decreased with malnutrition, so the total blood proportional to the decrease in skeletal muscle volume usually falls.23'37 In Keys and coworkers' bulk. studies the total blood volume had decreased an As myocardial mass decreases in starvation, average of 8.6% and the venous pressure more stroke volume and cardiac output fall proportion- than 50% at the height of starvation.'7"18'23 In 754 CMAJ, VOL. 135, OCTOBER 1, 1986 addition to the low levels of catecholamines found increasing energy expenditure and demands on in starved patients, deiodination of thyroxine to cardiac output.47 Even minor degrees of pulmonary triiodothyronine is impaired. Both factors may congestion can have significant effects on the contribute to the decreased metabolic rate of pro- requirements of the respiratory muscles for energy tein-calorie malnutrition and, hence, the decreased and oxygen.48 Decreased tissue perfusion or hypox- demands on the heart.28 emia and, hence, diminished peripheral oxygen Since multiple factors may compensate for the delivery can result in impaired aerobic glycolysis cardiac atrophy of protein-calorie malnutrition, and inefficient use of energy. Low cardiac output when might the effects of starvation on the heart itself produces fatigue and weakness, which may be clinically important? Three situations should be be compounded by the effects of diuretics on considered: the patient with chronic cardiac failure sodium, potassium and magnesium balance. These and cardiac cachexia; the patient exposed to in- factors, in addition to the decreased palatability of creased metabolic demands such as those that may a low-sodium diet, age, depression and the an- occur with surgery or parenteral nutrition; and the orexigenic effect of cardiac drugs, may limit oral genesis of arrhythmias. intake.38 Chronic cardiac failure is often associated with an emaciated habitus, which indicates diminished Cardiac cachexia fat reserves and skeletal muscle. Patients with these features may have depressed serum protein Severe usually results in levels, anergy on skin testing and some myocardial some increase in cardiac mass as the heart attempts atrophy. Nutritional supplementation may benefit to cope with the increased demands placed on it. such malnourished, debilitated patients by improv- In some patients cardiac failure ensues and contrib- ing their resistance to , strength and sense utes toward a malnourished state associated with of well-being. Improved nutrition can reverse the myocardial atrophy. It was to describe this phe- myocardial atrophy of starvation.18"7 Heymsfield nomenon that Pittman and Cohen38 coined the and associates27 administered nutritional supple- term "cardiac cachexia". It has been shown that ments to five chronically malnourished patients, cardiac hypertrophy can be prevented in hyperten- and after 3 to 5 weeks the patients' body weight sive rats subjected to a diet deficient in protein.39 had increased 12%. The heart volume as assessed Reports on humans confirm the phenomenon of an radiographically, however, had increased 25%. absolutely or relatively decreased myocardial mass This was due to a 59% increase in diastolic volume in malnourished cardiac patients.40-43 and a 31% increase in left ventricular mass as There are many mechanisms whereby chronic determined by echocardiography. Associated with cardiac failure may lead to malnutrition (Fig. 1). this was a 90% increase in cardiac output. Similar Elevated right-sided venous pressure produces he- findings have been reported in starved animals and patic and gastrointestinal congestion and, hence, humans and in humans with kwashiorkor. Howev- anorexia, diminished synthetic capacity and malab- er, after correction of severe starvation, cardiac sorption." Both hepatic congestion and diminished function may not return entirely to normal.25'3749 perfusion may produce a clinical picture resem- Whether aggressive nutritional support can pro- bling acute hepatitis.45 Splanchnic congestion can vide substantial improvement in cardiac function result in dyspepsia, malabsorption, maldigestion in the patient with cardiac cachexia has not been and protein-losing enteropathy.46 Elevated renal established. However, it is possible that in selected vein pressures lead to increased renal protein patients nutritional support may be beneficial. wastage. Pulmonary congestion can markedly in- crease lung stiffness, which increases the work of breathing. With congestive the meta- Malnutrition and cardiac surgery bolic demands of the respiratory musculature can increase from less than 5% to more than 25% of The role of malnutrition as a significant risk the total oxygen consumption of the body, thereby factor in major surgery is well established.50-52 Patients with recent weight loss, poor oral intake, malabsorption, low serum protein levels and aner- CARDIAC FAILURE gy on skin testing are now frequently given paren- teral nutrition before many surgical procedures. Cri/ Metabolic Few studies have examined the cardiac Cardiac Abnormalities f Venous specifically Output _ + Pressure patient. MALNUTRITION In 1976 Abel and collaborators42 described the outcome of cardiac surgery in 44 malnourished CARDIAC CACHEXIA patients. The mortality rate was 16%, whereas General M , / there were no deaths in a matched group of Debility MYOCARDIAALAATROPHY well-nourished patients. The most frequent com- plications were pneumonia, respiratory failure, Fig. 1 - Cardiac cachexia: cardiac failure leads to poor renal failure and mediastinitis. Routine postopera- nutrition and relative myocardial atrophy. tive parenteral nutrition was of no benefit.43 In a

CMAJ, VOL. 135, OCTOBER 1, 1986 755 later study the same group showed that the results of cardiac atrophy and the ability to generate of routine nutritional assessment correlated poorly cardiac output may not keep pace with these with the outcome of cardiac surgery and that such rapidly increasing demands. assessment was not useful in individual patients.53 Cardiac failure is a concern in nutritionally However, most patients were suffering from is- supplemented patients even when the sodium and chemic coronary disease, a condition infrequently water load is kept low. It is important to begin associated with significant malnutrition. with low energy loads in patients at risk of cardiac Gibbons and Blackburn and their associ- decompensation. It may be useful in these patients ates40,41 reported on a series of 12 clinically mal- to give a higher proportion of energy as fat rather nourished patients who underwent cardiac valve than carbohydrate. The lower respiratory quotient replacement. Those who received preoperative nu- of fat oxidation results in less carbon dioxide tritional supplementation were more likely to sur- production, thereby decreasing the work of breath- vive surgery than those who did not. The authors ing and facilitating ventilator weaning in patients felt that a 2- to 3-week period of nutritional with respiratory failure. The higher energy density supplementation was necessary to adequately im- of fat allows that less volume be given. Techniques prove nutritional status. This study, although of nutritional supplementation in cardiac patients small, suggests that preoperative nutritional sup- have been reviewed elsewhere.56 If these principles port may improve the survival rate of malnour- are remembered and the patient is closely moni- ished patients undergoing cardiac surgery. tored, cardiac failure should rarely be precipitated by parenteral nutrition. Refeeding and cardiac failure Genesis of arrhythmias Although congestive cardiac failure is rare in malnutrition, it is common during refeeding of the The publication of The Last Chance Diet,57 in starved patient. "Refeeding edema" and cardiac 1976, led to the popularity of a "very-low-calorie failure are well known with oral refeeding of liquid protein" diet. The US Centers for Disease severely malnourished patients.54 Edozien and Ra- Control estimated that during 1977 approximately him-Khan37 found that when children with pro- 100 000 Americans followed this diet for at least 1 tein-calorie malnutrition were fed a high-protein month58 and that there were about 60 associated milk diet their plasma volume increased, and in sudden deaths.59 Frank and coworkers60 reviewed 20% of the children congestive heart failure devel- the cases of 36 patients on this diet whose average oped. More recently, cardiac failure has been weight loss had been 30% over the 4 months recognized as a complication of total parenteral before death. They identified a pre-existing illness nutrition even in noncardiac patients.27 in 30 of the 36 and concluded that electrolyte or Starvation is associated with a fall in heart mineral deficiencies may have been significant in rate, blood pressure and blood volume; however, many of the deaths. refeeding is associated with a sudden reversal of Somewhat different findings were reported in these compensatory factors. Further, since severe a group of 17 previously healthy obese patients.21'6' malnutrition may result in interstitial myocardial These patients had lost an average of 34% of their edema, cardiac compliance may decrease.24'25 The premorbid weight over a period of 2 to 6 months; malnourished patient may not cope well with however, seven remained at least 20% over their increased salt, water and energy loads. Carbohy- ideal weight. All the patients were thought to have drate and fat are potent stimuli for the release of received adequate mineral and electrolyte supple- catecholamines and activation of the renin-an- ments under medical supervision. No consistent giotensin-aldosterone axis. This further increases abnormalities in magnesium or potassium levels blood volume and pressure.30'3' Energy intake re- were noted. Electrocardiograms obtained for 11 of verses the natriuresis of the fasting state.34-36 Fur- the 17 patients shortly before death revealed thermore, catecholamines augment the shift of ventricular in all 11. In eight who had potassium, magnesium and phosphate into cells, a 12-lead study the QT interval was prolonged, with potentially deleterious effects on cardiac func- which suggested delayed myocardial repolarization tion and rhythm. and a predisposition to arrhythmias. Evidence of Refeeding causes a change from the hypome- myocardial atrophy - attenuation of myocardial tabolism of starvation to the hypermetabolism of fibres and excessive lipofuscin - was noted, and refeeding. Increasing energy intake leads to corre- the heart weight was decreased in proportion to sponding increases in oxygen consumption, and to the body weight. This was thought to be consistent meet this demand cardiac output must increase. with protein-calorie malnutrition. Thus, a syn- Increased carbon dioxide production requires in- drome of myocardial atrophy, decreased QRS volt- creased respiratory ventilation and increased work age, a prolonged QT interval and ventricular of breathing.47'48 Heat production and heart rate arrhythmias was described. progressively rise with increasing energy intake. Interestingly, the duration of survival ap- With parenteral nutrition these measures of metab- peared to be proportional to the degree of obesity olism may rise above normal values.2855 Reversal at the onset of the diet.2' It is possible that the 756 CMAJ, VOL. 135, OCTOBER 1, 1986 fattest dieters survived the longest because they Braunwald E (ed): Heart Disease, Saunders, Toronto, 1984: were to some degree better able to conserve their 807-822 body protein and consequently their myocardial 2. Frustaci A, Pennestri F, Scoppetta C: Myocardial damage protein.62 In less obese dieters prolongation of the due to and hypophosphatemia. Postgrad Med QT interval occurs after a rapid weight loss of 10% J1984; 60: 679-681 3. Potts JL, Dalakos TG, Streeten DHP et al: Cardiomyopathy to 15%, whereas in more obese dieters it occurs in an adult with Bartter's syndrome and hypokalemia. Am J after a loss of 30% or greater.63 The cause of Cardiol 1977; 40: 995-999 in is prolongation of the QT interval this syndrome 4. O'Connor LR, Wheeler WS, Bethune JE: Effect of hypo- an enigma; however, subsequent studies have phosphatemia on myocardial performance in man. N Engi J demonstrated the safety of diets very low in Med 1977; 297: 901-903 energy that contain protein of better biologic 5. Keshan Disease Research Group of the Chinese Academy quality and more complete , mineral and of Medical Sciences, Beijing: Observations on effect of electrolyte supplements.64-66 It seems that loss of sodium selenite in prevention of Keshan disease. Chin Med myocardial protein and cardiac atrophy are impor- J[Engl] 1979; 92: 471-476 tant in the syndrome of sudden death associated 6. Idem: Epidemiologic studies on the etiologic relationship of with rapid weight loss.62 However, other factors selenium and Keshan disease. Ibid: 477-482 trace elements, vitamins, electrolytes, fatty acids or 7. johnson RA, Baker SS, Fallon JT et al: An occidental case of the autonomic effects of starvation - may be cardiomyopathy and . N Engi J Med involved.64-67 1981; 304: 1210-1212 Sudden death does not appear to be a syn- 8. Quercia RA, Korn S, O'Neill D et al: Selenium deficiency drome peculiar to the liquid protein diet.68 There and fatal cardiomyopathy in a patient receiving long-term have been other reports of a prolonged QT interval home parenteral nutrition. Clin Pharm 1984; 3: 531-535 and ventricular arrhythmias, particularly torsade 9. Fleming CR, Lie JT, McCall JT et al: Selenium deficiency and fatal cardiomyopathy in a patient on home parenteral de pointes, in obese people with rapid weight loss nutrition. Gastroenterology 1982; 83: 689-693 due to fasting29'63'69 and in anorexia nervosa.22 It 10. Bistrian BR: Anthropometric norms used in assessment of has been suggested that an electrocardiogram hospitalized patients. Am Clin Nutr 1980; 33: 2211-2214 should be obtained from patients with recent J 11. Blackburn GL, Harvey KB: Nutritional assessment as a significant weight loss,22'62'70 evidence of serious in clinical medicine. Postgrad Med 1982; 71: 46-63 arrhythmias or a prolonged QT interval being the routine criterion for more aggressive management, includ- 12. Miller CL: Immunological assays as measurements of nutri- ing electrocardiographic monitoring and nutritional tional status: a review. JPEN 1978; 2: 554-566 13. Meakins JL, Pietsch JB, Bubenik 0 et al: Delayed hypersen- supplementation. sitivity: indicator of acquired failure of host defences in sepsis and trauma. Arch Surg 1977; 186: 241-250 14. Bistrian BR, Blackburn GL, Vitale J et al: Prevalence of Conclusions malnutrition in general medical patients. JAMA 1976; 235: 1567-1570 The heart is not spared in malnutrition. The 15. Weinsier RL, Hunker EM, Krumdieck CL et al: Hospital decrease in cardiac output in the starved patient is malnutrition: a prospective evaluation of general medical matched by various compensatory mechanisms patients during the course of hospitalization. Am l Clin such that cardiac failure is unusual. With refeeding, Nutr 1979; 32: 418-426 reversal of these mechanisms occurs and conges- 16. Voit C: Ueber die Verschiedenheiten der Eiwesszersetzung tive heart failure may be precipitated before the beim Hungern. Z Biol 1866; 2: 309-365 reversal of myocardial atrophy, even in the ab- 17. Keys A, Henschel A, Taylor HL: The size and function of sence of other cardiac disease. The malnourished the human heart at rest in semi-starvation and in subse- patient is at increased risk during major surgery, quent rehabilitation. Am J Physiol 1947; 50: 153-169 and preoperative nutritional therapy may be indi- 18. Keys A, Brosek J, Henschel A et al (eds): Circulation and cardiac function. In The Biology of Human Starvation, U of cated. Chrdnic cardiac failure often results in a Minn Pr, Minneapolis, 1950: 607-634 malnourished state and, hence, relative myocardial 19. Bloom WL, Azar G, Smith EG Jr: Changes in heart size and atrophy. Cardiac cachexia and associated cardiac plasma volume during fasting. Metabolism 1966; 15: 409- dysfunction may be improved with better nutri- 413 tion. Rapid weight loss and malnutrition may also 20. Smythe PM, Swanepoel A, Campbell JA: The heart in be associated with a syndrome of myocardial kwashiorkor. Br MedJ 1962; 1: 67-73 atrophy, a prolonged QT interval, ventricular ar- 21. Isner JM, Sours HE, Paris AL et al: Sudden unexpected rhythmias and sudden death. 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758 CMAJ, VOL. 135, OCTOBER 1, 1986 For prescribing information see page 820 -