Key Points Question Do high-risk African children with severe malnutrition show abnormal myocardial function consistent with biventricular failure and/or life-threatening arrhythmias? Findings In a longitudinal case-control study of 88 children with severe, acute malnutrition, no evidence was found that malnourished children were at greater risk of cardiac dysfunction or clinically significant arrhythmias than nonmalnourished controls. Myocardial function was similar in the 2 marasmus and kwashiorkor clinical phenotypes, and myocardial indices following intravenous rehydration indicated fluid-responsive changes with no child developing fluid overload. Meaning Research is needed to address current guidelines restricting rehydration for severe gastroenteritis to oral therapy., Importance Mortality among African children hospitalized with severe malnutrition remains high, with sudden, unexpected deaths leading to speculation about potential cardiac causes. Malnutrition is considered high risk for cardiac failure, but evidence is limited. Objective To investigate the role of cardiovascular dysfunction in African children with severe, acute malnutrition (SAM). Design, Setting, and Participants A prospective, matched case-control study, the Cardiac Physiology in Malnutrition (CAPMAL) study, of 88 children with SAM (exposed) vs 22 severity-matched patients without SAM (unexposed) was conducted between March 7, 2011, and February 20, 2012; data analysis was performed from October 1, 2012, to March 1, 2016. Exposures Echocardiographic and electrocardiographic (ECG) recordings (including 7-day Holter monitoring) at admission, day 7, and day 28. Main Outcomes and Measures Findings in children with (cases) and without (controls) SAM and in marasmus and kwashiorkor phenotypes were compared. Results Eighty-eight children (52 with marasmus and 36 with kwashiorkor) of the 418 admitted with SAM and 22 severity-matched controls were studied. A total of 63 children (57%) were boys; median age at admission was 19 months (range, 12-39 months). On admission, abnormalities more common in cases vs controls included severe hypokalemia (potassium 4.2 mU/L) (18 of 74 [24%] vs 1 of 21 [5%]) and were associated with typical electrocardiographic changes (T-wave inversion: odds ratio, 7.3; 95% CI, 1.9-28.0; P = .001), which corrected as potassium levels improved. Fourteen children with SAM (16%) but no controls died. Myocardial mass was lower in cases on admission but not by day 7. Results of the Tei Index, a measure of global cardiac function, were within the reference range and similar in cases (median, 0.37; interquartile range [IQR], 0.26-0.45) and controls (median, 0.36; IQR, 0.28-0.42). Echocardiography detected no evidence of cardiac failure among children with SAM, including those receiving intravenous fluids to correct hypovolemia. Cardiac dysfunction was generally associated with comorbidity and typical of hypovolemia, with low cardiac index (median, 4.9 L/min/m2; IQR, 3.9-6.1 L/min/m2), high systemic vascular resistance index (median, 1333 dyne seconds/cm5/m2; IQR, 1133-1752 dyne seconds/cm5/m2), and with few differences between the marasmus and kwashiorkor manifestations of malnutrition. Seven-day continuous ECG Holter monitoring during the high-risk initial refeeding period demonstrated self-limiting significant ventricular arrhythmias in 33 of 55 cases (60%) and 6 of 18 controls (33%) (P = .049); none were temporally related to adverse events, including fatalities. Conclusions and Relevance There is little evidence that African children with SAM are at greater risk of cardiac dysfunction or clinically significant arrhythmias than those without SAM or that marasmus and kwashiorkor differed in cardiovascular profile. These findings should prompt a review of current guidelines., This case-control study examines the risk for cardiac dysfunction in African children hospitalized for severe, acute malnutrition.