Major rapid weight loss induces changes in cardiac repolarization☆
Introduction
Overweight and obesity are associated with increased all-cause mortality [1]. Thus, achieving a healthy body weight is a primary strategy for the prevention and management of obesity-related comorbidities [2]. However, weight loss due to intensive lifestyle change is not associated with a decrease in the number of cardiovascular events, at least not in individuals with established or incipient cardiovascular disease [3]. Furthermore, rapid weight loss has been shown to induce adverse changes in cardiac repolarization during very low calorie diets [4], and has in some cases been linked to arrhythmias and sudden death in healthy obese individuals [4], [5], [6].
It is well known that a prolonged cardiac QT interval is associated with an increased risk of torsades de pointes ventricular tachycardia (TdP) which may degenerate into lethal arrhythmias. Therefore, the QT interval is an important parameter when assessing arrhythmic risk [7]. As a consequence, monitoring the ECG during weight loss with low calorie diets in eating disorders has been recommended, even in the absence of electrolyte disturbances [5], [8]. However, it is known from studies of the long QT syndrome (LQT) and drug-induced LQT that some patients will develop torsades de pointes despite having a normal QT interval [9].
Changes in T-wave morphology have been suggested to be more sensitive markers of repolarization disturbances than the QT interval [10] and T-wave morphology algorithms have recently received FDA 510(k) approval [11]. Furthermore, independent studies from FDA have recently associated T-wave morphology changes with drugs known for their arrhythmic risk [12]. The T-wave Morphology Combination Score (MCS) is a quantitative marker, which increases during blockade of the delayed rectifier HERG potassium channel (Kv11.1) [13]. Thus, increases in MCS may be associated with increased blockage of HERG channels [13], [14], which may imply an increased risk of arrhythmias. Furthermore, both hypo- and hyperglycemia have been associated with HERG blockade [15], indicating that glycemic perturbations may interact with cardiac repolarization. In addition, LQT patients with loss of function mutations in the voltage-gated potassium channel KCNQ1 experience both hypoglycemia and repolarization disturbances [16], further indicating a link between metabolism and cardiac repolarization. Also, hypoglycemia is associated with increased mortality rates and sudden death [17].
Therefore, the purpose of this study was to assess the effect of a major and rapid weight loss [18] on the QT interval and T-wave morphology. The association between ECG parameters and glucose metabolism was also investigated.
Section snippets
Study design
The participants followed a low calorie diet (810 kilocalories per day, Cambridge Weight Plan Products ®) for 8 weeks. The dietary energy distribution was 46% from carbohydrate, 41% from protein, and 13% from fat. Daily intake of protein was at least 43.2 g, and intake of the essential fatty acids, linoleic and linolenic acid, was 3 g and 0.4 g, respectively. Dietary fiber intake was 7.2 g per day at minimum and the diet met all recommendations for daily intake of vitamins and minerals.
Fasting blood
Results
Table 1 shows the demographics of the participants included in the study.
During the 8 weeks of dieting, there was a significant decrease in body weight (p < 0.001). On average, the participants obtained a weight loss of 11.8 ± 0.5 kg during the 8 weeks (13.4 ± 0.6% body weight). Systolic blood pressure decreased significantly (− 8 ± 2 mm Hg, p < 0.05), but not diastolic blood pressure (− 5 ± 2 mm Hg, NS). Both fasting glucose and HbA1c decreased significantly (Table 2).
When inspecting the ECGs visually, inverted
Discussion
We find repolarization changes during a major and rapid weight loss when measured by the T-wave morphology parameter MCS but not when measured using the standard QTcF assessment. This is in line with studies suggesting that MCS is a more sensitive marker of repolarization changes than QTcF [13], [14]. A study of elite athletes has shown that large changes in MCS may occur despite no changes in QTc [19]. In agreement, the present study found a small insignificant increase in QTcF of 1 ms, but a
Limitations
We cannot exclude an effect of micronutritional imbalances due to the diet because the study lacks a control group with no weight loss. However, the diet followed all recommendations on intake of vitamins and minerals, making such disturbances less likely. We used a simple QT correction method because of the short 10 second recording segments and the relatively small range of heart rates during rest. Better individual correction methods exists [34], if it had been possible to apply Holter
Conclusion
Rapid weight loss induces changes in cardiac repolarization. Monitoring of MCS during calorie restriction makes it possible to detect repolarization changes with higher discriminative power than the QT-interval during major rapid weight loss interventions. MCS was correlated with decreased HbA1c. Thus, sustained low blood glucose levels may contribute to repolarization changes.
Acknowledgements
CG, JJS, and JKK are inventors of a patent regarding T-wave morphology. The remaining authors declare no conflict of interest.
The work was supported by funding from the Danish Strategic Research Foundation (HEARTSAFE) the Fraenkel Foundation, the Danish Research Council, Health and Disease, the University Investment Capital (UNIK): Food, Fitness and Pharma for Health and Disease from the Danish Ministry of Science, Technology and Innovation and The Danish Diabetes Academy supported by the Novo
References (34)
Cardiac effects of starvation and semistarvation diets: safety and mechanisms of action
Am J Clin Nutr
(1992)- et al.
Impairment of human ether-a-go-go-related gene (HERG) K + channel function by hypoglycemia and hyperglycemia. Similar phenotypes but different mechanisms
J Biol Chem
(2003) - et al.
T-wave morphology analysis of competitive athletes
J Electrocardiol
(2015) - et al.
The morphology of the QT interval predicts torsade de pointes during acquired bradyarrhythmias
J Am Coll Cardiol
(2007) - et al.
Effect of weight loss on the ECG of normotensive morbidly obese patients*
Chest
(2001) - et al.
Hypoglycaemia and QT interval prolongation in type 1 diabetes—bridging the gap between clamp studies and spontaneous episodes
J Diabetes Complications
(2014) - et al.
Body-mass index and mortality among 1.46 million white adults
N Engl J Med
(2010) - et al.
Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association
Diabetes Care
(2008) Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes
N Engl J Med
(2013)- et al.
Sudden, unexpected death in avid dieters using the liquid-protein-modified-fast diet. Observations in 17 patients and the role of the prolonged QT interval
Circulation
(1979)
Starvation diets as a cause of acquired long QT syndrome
Ann Intern Med
QT interval prolongation and the risk of torsades de pointes: essentials for clinicians
Curr Med Res Opin
Heart risk associated with weight loss in anorexia nervosa and eating disorders: risk factors for QTc interval prolongation and dispersion
Acta Paediatr
What clinicians should know about the QT interval
JAMA
Covariate analysis of QTc and T-wave morphology: new possibilities in the evaluation of drugs that affect cardiac repolarization
Clin Pharmacol Ther
510(k) Premarket Notification. U.S. Food and Drug Administration
Comprehensive T wave morphology assessment in a randomized clinical study of dofetilide, quinidine, ranolazine, and verapamil
J Am Heart Assoc
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Author contributions: ST, EVL, TH, JJH, JKK and SM designed and planned the study. EWI and JL collected the data. All authors took part in data analysis/interpretation, drafting and approval of the article. Statistics were performed by EVL, JKK. Data analysis/interpretation, EVL, ST, JKK. Drafting article, EVL, ST, EWI, SM, JL, JJS, CG, JJH, TH, JKK. Critical revision of article, EVL, ST, EWI, SM, JL, JJS, CG, JJH, TH, JKK. Approval of article, EVL, ST, EWI, SM, JL, JJS, CG, JJH, TH, JKK. Statistics was performed by EVL, ST, and JKK. Funding secured by JJH, ST, SM, JK.
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These authors contributed equally to the manuscript.