Nonalcoholic fatty liver disease (NAFLD) is a common, progressive liver disease that affects up to one-quarter of the adult population worldwide. The clinical and economic burden of NAFLD is mainly ...due to liver-related morbidity and mortality (nonalcoholic steatohepatitis, cirrhosis or hepatocellular carcinoma) and an increased risk of developing fatal and nonfatal cardiovascular disease, chronic kidney disease and certain types of extrahepatic cancers (for example, colorectal cancer and breast cancer). Additionally, there is now accumulating evidence that NAFLD adversely affects not only the coronary arteries (promoting accelerated coronary atherosclerosis) but also all other anatomical structures of the heart, conferring an increased risk of cardiomyopathy (mainly left ventricular diastolic dysfunction and hypertrophy, leading to the development of congestive heart failure), cardiac valvular calcification (mainly aortic-valve sclerosis), cardiac arrhythmias (mainly atrial fibrillation) and some cardiac conduction defects. This Review focuses on the association between NAFLD and non-ischaemia-related cardiac disease, discusses the putative pathophysiological mechanisms and briefly summarizes current treatment options for NAFLD that might also beneficially affect cardiac disease.
Summary Background Defibrillation testing by induction and termination of ventricular fibrillation is widely done at the time of implantation of implantable cardioverter defibrillators (ICDs). We ...aimed to compare the efficacy and safety of ICD implantation without defibrillation testing versus the standard of ICD implantation with defibrillation testing. Methods In this single-blind, randomised, multicentre, non-inferiority trial (Shockless IMPLant Evaluation SIMPLE), we recruited patients aged older than 18 years receiving their first ICD for standard indications at 85 hospitals in 18 countries worldwide. Exclusion criteria included pregnancy, awaiting transplantation, particpation in another randomised trial, unavailability for follow-up, or if it was expected that the ICD would have to be implanted on the right-hand side of the chest. Patients undergoing initial implantation of a Boston Scientific ICD were randomly assigned (1:1) using a computer-generated sequence to have either defibrillation testing (testing group) or not (no-testing group). We used random block sizes to conceal treatment allocation from the patients, and randomisation was stratified by clinical centre. Our primary efficacy analysis tested the intention-to-treat population for non-inferiority of no-testing versus testing by use of a composite outcome of arrhythmic death or failed appropriate shock (ie, a shock that did not terminate a spontaneous episode of ventricular tachycardia or fibrillation). The non-inferiority margin was a hazard ratio (HR) of 1·5 calculated from a proportional hazards model with no-testing versus testing as the only covariate; if the upper bound of the 95% CI was less than 1·5, we concluded that ICD insertion without testing was non-inferior to ICD with testing. We examined safety with two, 30 day, adverse event outcome clusters. The trial is registered with ClinicalTrials.gov , number NCT00800384. Findings Between Jan 13, 2009, and April 4, 2011, of 2500 eligible patients, 1253 were randomly assigned to defibrillation testing and 1247 to no-testing, and followed up for a mean of 3·1 years (SD 1·0). The primary outcome of arrhythmic death or failed appropriate shock occurred in fewer patients (90 7% per year) in the no-testing group than patients who did receive it (104 8% per year; HR 0·86, 95% CI 0·65–1·14; pnon-inferiority <0·0001). The first safety composite outcome occurred in 69 (5·6%) of 1236 patients with no-testing and in 81 (6·5%) of 1242 patients with defibrillation testing, p=0·33. The second, pre-specified safety composite outcome, which included only events most likely to be directly caused by testing, occurred in 3·2% of patients with no-testing and in 4·5% with defibrillation testing, p=0·08. Heart failure needing intravenous treatment with inotropes or diuretics was the most common adverse event (in 20 2% of 1236 patients in the no-testing group vs 28 2% of 1242 patients in the testing group, p=0·25). Interpretation Routine defibrillation testing at the time of ICD implantation is generally well tolerated, but does not improve shock efficacy or reduce arrhythmic death. Funding Boston Scientific and the Heart and Stroke Foundation (Ontario Provincial office).
Ventricular arrhythmia (VA) in structurally normal hearts can be broadly considered under non–life-threatening monomorphic and life-threatening polymorphic rhythms. Monomorphic VA is classified on ...the basis of site of origin in the heart, and the most common areas are the ventricular outflow tracts and left ventricular fascicles. The morphology of the QRS complexes on electrocardiogram is an excellent tool to identify the site of origin of the rhythm. Although these arrhythmias are common and generally carry an excellent prognosis, rare sudden death events have been reported. Very frequent ventricular ectopy may also result in a cardiomyopathy in a minority of patients. Suppression of VA may be achieved using calcium-channel blockers, beta-adrenergic blockers, and class I or III antiarrhythmic drugs. Radiofrequency ablation has emerged as an excellent option to eliminate these arrhythmias, although certain foci including aortic cusps and epicardium may be technically challenging. Polymorphic ventricular tachycardia (VT) is rare and generally occurs in patients with genetic ion channel disorders including long QT syndrome, Brugada syndrome, catecholaminergic polymorphic VT, and short QT syndrome. Unlike monomorphic VT, these arrhythmic syndromes are associated with sudden death. While the cardiac gross morphology is normal, suggesting a structurally normal heart, abnormalities exist at the molecular level and predispose them to arrhythmias. Another fascinating area, idiopathic ventricular fibrillation and early repolarization syndrome, are undergoing research for a genetic basis.
ABSTRACT
While long‐distance running has important health benefits, chronic elevation of blood pressure during exercise might induce cardiac events and sudden death. This study aimed to investigate ...characteristics of exercise and incidence of abnormal exercise electrocardiography findings in long‐distance runners with exercise‐induced hypertension. Long‐distance runners (n = 606) underwent a questionnaire survey, history taking, and exercise stress testing, and they were classified into the non‐exercise‐induced (n = 268) and exercise‐induced (n = 338) hypertension groups. Exercise‐induced hypertension was defined as systolic blood pressure ≥210 mm Hg during maximal exercise. Abnormal electrocardiogram response (AER) were defined as abnormal electrocardiography findings, such as arrhythmias or ST‐segment changes, during exercise stress testing. There were no differences in general and exercise‐related characteristics between the non‐exercise‐induced and exercise‐induced hypertension groups. The AER group (AERg, n = 37) had a significantly longer training history and total exercise time than the non‐AER group (non‐AERg, n = 569) (p < .05). Atrial arrhythmias and ST‐segment depression were more prevalent in the exercise‐induced hypertension group than in the non‐exercise‐induced hypertension group (atrial arrhythmias: 5% 17/338 vs. 1.9% 5/268; ST‐segment depression: 2.7% 9/338 vs. .4% 1/268; p < .05). The incidence of AER was significantly higher in the exercise‐induced hypertension group (n = 30, 8.8%) than in the non‐exercise‐induced hypertension group (n = 7, 2.6%) (p < .05). This study showed that long‐distance runners with AER had a longer training history and total exercise time than those without AER, and the exercise‐induced hypertension group had a higher rate of AER.
Previous research found an association of CRP with QT time in population based samples. Even more, there is evidence of a substantial involvement of the tumor necrosis factor-alpha system in the ...pathophysiology of cardiac arrhythmia, while the role of Interleukin 6 remains inconclusive.
To determine the association between inflammation with an abnormally prolonged QT-time (APQT) in men and women of the elderly general population.
Data descend from the baseline examination of the prospective, population-based Cardiovascular Disease, Living and Ageing in Halle (CARLA) Study. After exclusion of subjects with atrial fibrillation and missing ECG recording the final study cohort consisted of 919 men and 797 women. Blood parameters of inflammation were the soluble TNF-Receptor 1 (sTNF-R1), the high-sensitive C-reactive protein (hsCRP), and Interleukin 6 (IL-6). In accordance with major cardiologic societies we defined an APQT above a QT time of 460 ms in women and 450 ms in men. Effect sizes and the corresponding 95% confidence intervals (CI) were estimated by performing multiple linear and logistic regression analyses including the analysis of sex differences by interaction terms.
After covariate adjustment we found an odds ratio (OR) of 1.89 (95% CI: 1.13, 3.17) per 1000 pg/mL increase of sTNF-R1 in women, and 0.74 (95% CI: 0.48, 1.15) in men. In the covariate adjusted linear regression sTNF-R1 was again positively associated with QT time in women (5.75 ms per 1000 pg/mL, 95% CI: 1.32, 10.18), but not in men. Taking possible confounders into account IL-6 and hsCRP were not significantly related to APQT in both sexes.
Our findings from cross-sectional analyses give evidence for an involvement of TNF-alpha in the pathology of APQT in women.
Guidelines recommend the use of implanted cardioverter-defibrillators in patients with Brugada syndrome and induced ventricular tachyarrhythmias, but there is no evidence supporting it.
This ...prospective registry study was designed to explore clinical and electrophysiological predictors of malignant ventricular tachyarrhythmia inducibility in Brugada syndrome.
A total of 191 consecutive selected patients with (group 1; n = 88) and without (group 2; n = 103) Brugada syndrome–related symptoms were prospectively enrolled in the registry. Patients underwent electrophysiological study and substrate mapping or ablation before and after ajmaline testing (1 mg/kg/5 min).
Overall, before ajmaline testing, 53.4% of patients had ventricular tachyarrhythmia inducibility, which was more frequent in group 1 (65.9%) than in group 2 (42.7%; p < 0.001). Regardless of clinical presentation, larger substrates with more fragmented long-duration ventricular potentials were found in patients with inducible arrhythmias than in patients without inducible arrhythmias (p < 0.001). One extrastimulus was used in more extensive substrates (median 13 cm2; p < 0.001), and ventricular fibrillation was the more frequently induced rhythm (p < 0.001). After ajmaline, patients without arrhythmia inducibility had arrhythmia inducibility without a difference in substrate characteristics between the 2 groups. The substrate size was the only independent predictor of inducibility (odds ratio: 4.51; 95% confidence interval: 2.51 to 8.09; p < 0.001). A substrate size of 4 cm2 best identified patients with inducible arrhythmias (area under the curve: 0.98; p < 0.001). Substrate ablation prevented ventricular tachyarrhythmia reinducibility.
In Brugada syndrome dynamic substrate variability represents the pathophysiological basis of lethal ventricular tachyarrhythmias. Substrate size is independently associated with arrhythmia inducibility, and its determination after ajmaline identifies high-risk patients missed by clinical criteria. Substrate ablation is associated with electrocardiogram normalization and not arrhythmia reinducibility. (Epicardial Ablation in Brugada Syndrome BRUGADA_I; NCT02641431; Epicardial Ablation in Brugada Syndrome: An Extension Study of 200 BrS Patients; NCT03106701)
Display omitted
The incidence of life-threatening ventricular arrhythmias, the most common cause of sudden cardiac death (SCD), depends largely on the arrhythmic substrate that develops in the myocardium during the ...aging process. There is a large deficit of comparative studies on the development of this substrate in both sexes, with a particular paucity of studies in females. To identify the substrates of arrhythmia, fibrosis, cardiomyocyte hypertrophy, mitochondrial density, oxidative stress, antioxidant defense and intracellular Ca
signaling in isolated cardiomyocytes were measured in the hearts of 3- and 24-month-old female and male rats. Arrhythmia susceptibility was assessed in ex vivo perfused hearts after exposure to isoproterenol (ISO) and hydrogen peroxide (H
O
). The number of ventricular premature beats (PVBs), ventricular tachycardia (VT) and ventricular fibrillation (VF) episodes, as well as intrinsic heart rate, QRS and QT duration, were measured in ECG signals recorded from the surfaces of the beating hearts. After ISO administration, VT/VFs were formed only in the hearts of males, mainly older ones. In contrast, H
O
led to VT/VF formation in the hearts of rats of both sexes but much more frequently in older males. We identified several components of the arrhythmia substrate that develop in the myocardium during the aging process, including high spontaneous ryanodine receptor activity in cardiomyocytes, fibrosis of varying severity in different layers of the myocardium (nonheterogenic fibrosis), and high levels of oxidative stress as measured by nitrated tyrosine levels. All of these elements appeared at a much greater intensity in male individuals during the aging process. On the other hand, in aging females, antioxidant defense at the level of H
O
detoxification, measured as glutathione peroxidase expression, was weaker than that in males of the same age. We showed that sex has a significant effect on the development of an arrhythmic substrate during aging. This substrate determines the incidence of life-threatening ventricular arrhythmias in the presence of additional stimuli with proarrhythmic potential, such as catecholamine stimulation or oxidative stress, which are constant elements in the pathomechanism of most cardiovascular diseases.
The present study was to investigate the effects and mechanism of Luteolin on myocardial infarct size, cardiac function and cardiomyocyte apoptosis in diabetic rats with myocardial ...ischemia/reperfusion (I/R) injury.
Diabetic rats underwent 30 minutes of ischemia followed by 3 h of reperfusion. Animals were pretreated with or without Luteolin before coronary artery ligation. The severity of myocardial I/R induced LDH release, arrhythmia, infarct size, cardiac function impairment, cardiomyocyte apoptosis were compared. Western blot analysis was performed to elucidate the target proteins of Luteolin. The inflammatory cytokine production were also examined in ischemic myocardium underwent I/R injury. Our results revealed that Luteolin administration significantly reduced LDH release, decreased the incidence of arrhythmia, attenuated myocardial infarct size, enhanced left ventricular ejection fraction and decreased myocardial apoptotic death compared with I/R group. Western blot analysis showed that Luteolin treatment up-regulated anti-apoptotic proteins FGFR2 and LIF expression, increased BAD phosphorylation while decreased the ratio of Bax to Bcl-2. Luteolin treatment also inhibited MPO expression and inflammatory cytokine production including IL-6, IL-1a and TNF-a. Moreover, co-administration of wortmannin and Luteolin abolished the beneficial effects of Luteolin.
This study indicates that Luteolin preserves cardiac function, reduces infarct size and cardiomyocyte apoptotic rate after I/R injury in diabetic rats. Luteolin exerts its action by up-regulating of anti-apoptotic proteins FGFR2 and LIF expression, activating PI3K/Akt pathway while increasing BAD phosphorylation and decreasing ratio of Bax to Bcl-2.
Patients carrying loss-of-function SCN5A mutations linked to Brugada syndrome (BrS) or progressive cardiac conduction disease (PCCD) are at risk of sudden cardiac death at a young age. The penetrance ...and expressivity of the disease are highly variable, and new tools for risk stratification are needed.
We aimed to establish whether the type of SCN5A mutation correlates with the clinical and electrocardiographic phenotype.
We studied BrS or PCCD probands and their relatives who carried a SCN5A mutation. Mutations were divided into 2 main groups: missense mutations (M) or mutations leading to premature truncation of the protein (T). The M group was subdivided according to available biophysical properties: M mutations with <or=90% (M(active)) or >90% (M(inactive)) peak I(Na) reduction were analyzed separately.
The study group was composed of 147 individuals with 32 different mutations. No differences in age and sex distribution were found between the groups. Subjects carrying a T mutation had significantly more syncopes than those with an M(active) mutation (19 of 75 versus 2 of 35, P = .03). Also, mutations associated with drastic peak I(Na) reduction (T and M(inactive) mutants) had a significantly longer PR interval, compared with M(active) mutations. All other electrocardiographic parameters were comparable. After drug provocation testing, both PR and QRS intervals were significantly longer in the T and M(inactive) groups than in the M(active) group.
In loss-of-function SCN5A channelopathies, patients carrying T and M(inactive) mutations develop a more severe phenotype than those with M(active) mutations. This is associated with more severe conduction disorders. This is the first time that genetic data are proposed for risk stratification in BrS.
PDF
