Out of hospital sudden cardiac death in Italy: a population-based case–control study

Filippi, Alessandro; Sessa, Emiliano; Mazzaglia, Giampiero; Pecchioli, Serena; Capocchi, Rachele; Caprari, F; Scivales, A.; Cricelli, Claudio

doi:10.2459/jcm.0b013e3282f2c9d0

Cited by 19 publications

(11 citation statements)

References 18 publications

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“…Besides, the occurrence of life-threatening cardiac arrhythmias and sudden cardiac death (SCD) is quite high in patients with dyslipidemia, diabetes mellitus, hypertension or obesity. Indeed, epidemiological studies have shown that obese and diabetic patients have approximately twice and three times the risk, respectively, of SCD compared with age-matched controls [5–7]. …”

Section: Introductionmentioning

confidence: 99%

Development and characterization of an experimental model of diet-induced metabolic syndrome in rabbit

et al. 2017

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Metabolic syndrome (MetS) has become one of the main concerns for public health because of its link to cardiovascular disease. Murine models have been used to study the effect of MetS on the cardiovascular system, but they have limitations for studying cardiac electrophysiology. In contrast, the rabbit cardiac electrophysiology is similar to human, but a detailed characterization of the different components of MetS in this animal is still needed. Our objective was to develop and characterize a diet-induced experimental model of MetS that allows the study of cardiovascular remodeling and arrhythmogenesis. Male NZW rabbits were assigned to control (n = 15) or MetS group (n = 16), fed during 28 weeks with high-fat, high-sucrose diet. We measured weight, morphological characteristics, blood pressure, glycaemia, standard plasma biochemistry and the metabolomic profile at weeks 14 and 28. Liver histological changes were evaluated using hematoxylin-eosin staining. A mixed model ANOVA or unpaired t-test were used for statistical analysis (P<0.05). Weight, abdominal contour, body mass index, systolic, diastolic and mean arterial pressure increased in the MetS group at weeks 14 and 28. Glucose, triglycerides, LDL, GOT-AST, GOT/GPT, bilirubin and bile acid increased, whereas HDL decreased in the MetS group at weeks 14 and 28. We found a 40% increase in hepatocyte area and lipid vacuoles infiltration in the liver from MetS rabbits. Metabolomic analysis revealed differences in metabolites related to fatty acids, energetic metabolism and microbiota, compounds linked with cardiovascular disease. Administration of high-fat and high-sucrose diet during 28 weeks induced obesity, glucose intolerance, hypertension, non-alcoholic hepatic steatosis and metabolic alterations, thus reproducing the main clinical manifestations of the metabolic syndrome in humans. This experimental model should provide a valuable tool for studies into the mechanisms of cardiovascular problems related to MetS, with special relevance in the study of cardiovascular remodeling, arrhythmias and SCD.

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Section: Introductionmentioning

confidence: 99%

Development and characterization of an experimental model of diet-induced metabolic syndrome in rabbit

et al. 2017

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“…More importantly, diabetes and obesity are associated with an increased risk of sudden cardiac death, which is often caused by ventricular arrhythmias 4–6 . The increased risk of sudden cardiac death is greater than the increased risk of myocardial infarction, suggesting that arrhythmic events are increased more than coronary events in obese and diabetic patients.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial oxidative stress during cardiac lipid overload causes intracellular calcium leak and arrhythmia

et al. 2016

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Background Diabetes and obesity are associated with an increased risk of arrhythmia and sudden cardiac death. Abnormal lipid accumulation is observed in cardiomyocytes of obese and diabetic patients, which may contribute to arrhythmia, but the mechanisms are poorly understood. A transgenic mouse model of cardiac lipid overload, the PPARg cardiac overexpression mouse, has long QT and increased ventricular ectopy. Objective We evaluated the hypothesis that the increase in ventricular ectopy during cardiac lipid overload is caused by abnormalities in calcium handling due to increased mitochondrial oxidative stress. Methods Ventricular myocytes were isolated from adult mouse hearts to record sparks and calcium transients. Mice were implanted with heart rhythm monitors for in vivo recordings. Results PPARg cardiomyocytes have more frequent triggered activity and increased sparks compared to control. Sparks and triggered activity are reduced by mitotempo, a mitochondrial-targeted antioxidant. This is explained by a significant increase in oxidation of RyR2. Calcium transients are increased in amplitude and SR calcium stores are increased in PPARg cardiomyocytes. Computer modeling of the cardiac action potential demonstrates that long QT contributes to increased SR calcium. Mitotempo decreased ventricular ectopy in vivo. Conclusions During cardiac lipid overload, mitochondrial oxidative stress causes increased SR calcium leak by oxidizing RyR2 channels. This promotes ventricular ectopy, which is significantly reduced in vivo by a mitochondrial-targeted anti-oxidant. These results suggest a potential role for mitochondrial-targeted anti-oxidants to prevent arrhythmia and sudden cardiac death in obese and diabetic patients.

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“…After adjusting for other cardiovascular risk factors, both diabetes and obesity confer an increased risk of sudden cardiac death 4-8 , and are associated with altered cardiomyocyte electrical properties, manifested by prolongation of the QRS and QT intervals 9-11 . The molecular mechanisms responsible for alterations in the electrical properties of cardiomyocytes and the increased incidence of sudden cardiac death have not been well elucidated.…”

Section: Introductionmentioning

confidence: 99%

Mice With Cardiac Overexpression of Peroxisome Proliferator–Activated Receptor γ Have Impaired Repolarization and Spontaneous Fatal Ventricular Arrhythmias

et al. 2011

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Background Diabetes and obesity, which confer an increased risk of sudden cardiac death, are associated with cardiomyocyte lipid accumulation and altered cardiac electrical properties, manifested by prolongation of the QRS duration and QT interval. It is difficult to distinguish the contribution of cardiomyocyte lipid accumulation versus the contribution of global metabolic defects to the increased incidence of sudden death and electrical abnormalities. Methods and Results In order to study the effects of metabolic abnormalities on arrhythmias without the complex systemic effects of diabetes and obesity, we studied cardiac-specific transgenic mice expressing PPARγ1 via the cardiac α-myosin heavy-chain promoter. The PPARγ-transgenic mice develop abnormal accumulation of intracellular lipids and die as young adults, prior to a significant reduction in systolic function. Using implantable ECG telemeters, we found that these mice have prolongation of the QRS and QT intervals, and spontaneous ventricular arrhythmias, including polymorphic ventricular tachycardia and ventricular fibrillation. Isolated cardiomyocytes demonstrated prolonged action potential duration caused by reduced expression and function of the potassium channels responsible for repolarization. Short-term exposure to pioglitazone, a PPARγ agonist, had no effect on mortality or rhythm in WT mice, but further exacerbated the arrhythmic phenotype and increased the mortality in the PPARγ TG mice. Conclusions Our findings support an important link between PPARγ activation, cardiomyocyte lipid accumulation, ion channel remodeling and increased cardiac mortality.

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Out of hospital sudden cardiac death in Italy: a population-based case–control study

Cited by 19 publications

References 18 publications

Development and characterization of an experimental model of diet-induced metabolic syndrome in rabbit

Development and characterization of an experimental model of diet-induced metabolic syndrome in rabbit

Mitochondrial oxidative stress during cardiac lipid overload causes intracellular calcium leak and arrhythmia

Mice With Cardiac Overexpression of Peroxisome Proliferator–Activated Receptor γ Have Impaired Repolarization and Spontaneous Fatal Ventricular Arrhythmias

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