Melatonin reduces reperfusion arrhythmias when administered before coronary occlusion, but in the clinical context of acute coronary syndromes, most of the therapies are administered at the time of reperfusion. Patients frequently have physiological modifications that can reduce the response to therapeutic interventions. This work determined whether acute melatonin administration starting at the moment of reperfusion protects against ventricular arrhythmias in Langendorff-perfused hearts isolated from fructose-fed rats (FFR), a dietary model of metabolic syndrome, and from spontaneous hypertensive rats (SHR). In both experimental models, we confirmed metabolic alterations, a reduction in myocardial total antioxidant capacity and an increase in arterial pressure and NADPH oxidase activity, and in FFR, we also found a decrease in eNOS activity. Melatonin (50 μm) initiated at reperfusion after 15-min regional ischemia reduced the incidence of ventricular fibrillation from 83% to 33% for the WKY strain, from 92% to 25% in FFR, and from 100% to 33% in SHR (P = 0.0361, P = 0.0028, P = 0.0013, respectively, by Fisher's exact test, n = 12 each). Although, ventricular tachycardia incidence was high at the beginning of reperfusion, the severity of the arrhythmias progressively declined in melatonin-treated hearts. Melatonin induced a shortening of the action potential duration at the beginning of reperfusion and in the SHR group also a faster recovery of action potential amplitude. We conclude that melatonin protects against ventricular fibrillation when administered at reperfusion, and these effects are maintained in hearts from rats exposed to major cardiovascular risk factors. These results further support the ongoing translation to clinical trials of this agent.

OBJECTIVE:

s: We investigated the significance of serum high-sensitivity cardiac troponin T (hs-cTnT) marker for prediction of adverse events in hypertrophic cardiomyopathy (HCM).

BACKGROUND:

Although serum cardiac troponins as sensitive and specific markers of myocardial injury have become well-established diagnostic and prognostic markers in acute coronary syndrome, the usefulness of hs-cTnT for prediction of cardiovascular events in patients with HCM is unclear.

METHODS:

We performed clinical evaluation including measurements of hs-cTnT in 183 consecutive patients with HCM.

RESULTS:

Of 183 HCM patients, 99 (54%) showed abnormal hs-cTnT values (> 0.014 ng/ml). During a mean follow-up period of 4.1 ± 2.0 years, 32 (32%) of the 99 patients in the abnormal hs-cTnT group but only 6 (7%) of 84 patients with normal hs-cTnT values suffered from cardiovascular events: cardiovascular deaths, unplanned heart failure admissions, sustained ventricular tachycardia, embolic events, and progression to New York Heart Association functional class III or IV status (hazard ratio (HR): 5.05, p < 0.001). Abnormal hs-cTnT value remained an independent predictor of these cardiovascular events after multivariate analysis (HR: 3.23, p = 0.012). Furthermore, in the abnormal hs-cTnT group, overall risk increased with increase in hs-cTnT value (HR: 1.89　/　hs-cTnT 1 standard deviation (SD) increase in the logarithmic scale, 95% CI: 1.13 to 3.15, p = 0.015 (SD = 0.59)).

CONCLUSIONS:

In patients with HCM, an abnormal serum concentration of hs-cTnT is an independent predictor of adverse outcome, and a higher degree of abnormality in hs-cTnT value is associated with a greater risk of cardiovascular events.

Background:

 The genetic background of catecholaminergic polymorphic ventricular tachycardia (CPVT) has been extensively investigated for the last decade in Western countries, but it remains unstudied in the Asian population.

Methods and Results:

 In 50 Japanese probands from unrelated families who satisfied clinical criteria for CPVT, genetic testing was conducted in all exons on 3 CPVT-related genes: cardiac ryanodine receptor 2 (RYR2), calsequestrin 2 (CASQ2) and inward rectifier potassium channel 2 (KCNJ2), and the clinical features between RYR2-genotyped and -non-genotyped patient groups were compared. Genetic and clinical evaluation was also done in 46 family members. In the genetic screening, 28 (18 novel) RYR2 (56.0%), 1 compound heterozygous CASQ2 (2.0%) and 1 KCNJ2 (2.0%) mutation carriers were identified. In the RYR2 mutation-positive group, the frequency of bidirectional ventricular tachycardia and the use of β-blockers were significantly higher than in the mutation-negative group. In contrast, there was no significant difference in supraventricular arrhythmias between the 2 groups. With regard to disease penetrance, the number of family members of RYR2-genotyped probands with a clinical diagnosis of CPVT was high.

Conclusions:

 Thirty gene mutation carriers were found for 3 genes in 50 probands clinically diagnosed as having CPVT. The penetrance of CPVT phenotype was significantly higher in RYR2 mutation carriers, thus RYR2 gene screening in CPVT patients would be indispensable to prevent unexpected cardiac sudden death of young family members.

BACKGROUND:

Conducting channels within scars form the substrate for infarct-related ventricular tachycardia (VT) and are targeted during catheter ablation. Whether the amount of left ventricular scar (LVS) affects outcomes after VT ablation is not known.

OBJECTIVE:

To test the hypothesis that increased LVS is associated with worsened clinical outcomes and reduced survival after VT ablation.

METHODS:

Patients with coronary artery disease, intrinsic AV nodal conduction and undergoing infarct-related VT ablation were studied. A validated 32-point scoring system was used to measure LVS from 12 lead ECGs. Primary endpoint was all-cause mortality or transplantation and the secondary endpoint was a composite of death, transplantation or readmission due to VT recurrence within 1 year of discharge.

RESULTS:

Of 356 patients undergoing 466 infarct-related VT ablations screened, 192 patients (84% male, 66 ± 11 years old, 52% prior CABG, EF 28 ± 11%) who underwent 245 procedures for VT (2.4 ± 1.5 VT/patient, 31% with VT storm, refractory to 2.7 ± 1.2 anti-arrhythmic drugs) between 1999 and 2009 were included. During mapping, all patients had low voltage areas. Mean LVS was 21.4 ± 15.0%. Over 3.4 ± 3.1 years, 78 (41%) patients reached the primary endpoint (73 deaths, 5 transplants). In the first year after discharge, the secondary endpoint was reached in 56 (29%) subjects. In a multivariate model, larger LVS (HR 1.03 for every 3% increase in LVS, p < 0.01), renal dysfunction (HR 2.66, p <0.01) and increased age (HR 1.05 per year, p < 0.01) predicted mortality whereas non-inducibility of any VT was protective. (HR 0.36, p < p 0.01) Larger LVS and renal dysfunction was associated with worsened 1 year outcomes whilst non-inducibility was protective.

CONCLUSION:

LVS burden, derived from 12 lead ECGs is a significant and independent predictor of mortality and clinical outcomes in subjects with infarct-related VT.

Danon disease is a rare X-linked lysosomal disease causing severe hypertrophic cardiomyopathy (LAMP2 cardiomyopathy) and an extremely poor prognosis in males, with several reported cases of sudden cardiac death despite the use of transvenous implantable cardioverter defibrillators (TV-ICD). We describe a case in which a TV-ICD was unable to defibrillate induced ventricular fibrillation (VF), but a wholly subcutaneous system (S-ICD) was successful in terminating induced VF and spontaneous ventricular tachycardia. These findings have relevance to the selection of device therapy in the management of these individuals and a wider group of young patients with severe hypertrophic cardiomyopathy.

This article reviews the strengths and limitations of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) as models of cardiac arrhythmias. Specifically, the article attempts to answer the following questions: Which clinical arrhythmias can be modeled by iPSC-CM? How well can iPSC-CM model adult ventricular myocytes? What are the strengths and limitations of published iPSC-CM arrhythmia models? What new mechanistic insight has been gained? What is the evidence that would support using iPSC-CM to personalize antiarrhythmic drug therapy? The review also discusses the pros and cons of using the iPSC-CM technology for modeling specific genetic arrhythmia disorders, such as long QT syndrome, Brugada Syndrome, or Catecholaminergic Polymorphic Ventricular Tachycardia.

Induced pluripotent stem cells offer the possibility to generate patient-specific stem cell lines from individuals affected by inherited disorders. Cardiomyocytes differentiated from such patient-specific induced pluripotent stem cells lines have been used to study the pathophysiology of arrhythmogenic heart diseases, such as the long-QT syndrome or catecholaminergic polymorphic ventricular tachycardia. Testing for unwanted drug side effects or tailoring medical treatment to the specific needs of individual patients with arrhythmogenic disorders may become future applications of this emerging technology.

Glucagon-like peptide-1 and its receptor agonist-exendin-4 (Ex-4) have been shown to provide beneficial effects for cardiovascular diseases. This study investigated the effects of Ex-4 on ischemia-induced ventricular arrhythmias in rats.Anesthetized male rats were once treated with Ex-4 (5 μg/kg, i.v.) 1 h before ischemia in the absence and/or presence of 5-hydroxydecanoic acid (5-HD, 10 mg/kg, i.v., a specific inhibitor of mitochondrial ATP-sensitive potassium [KATP] channels) which were once injected 10 min before ischemia. And then subjected to ischemia for 30 min. Ventricular arrhythmias were assessed.During the 30-min ischemia, Ex-4 significantly reduced the incidence of ventricular fibrillation (VF) (p < 0.05). The duration of ventricular tachycardia (VT) + VF, the number of VT + VF episodes and the severity of arrhythmias were all significantly reduced by Ex-4 compared to those in myocardial ischemia group (p < 0.05 for all). Administration of 5-HD abolished the protective effects of Ex-4 on VF incidence, the duration of VT + VF, the number of VT + VF episodes and the severity of arrhythmias (p < 0.05 for all).This study suggested that Ex-4 could attenuate ischemia-induced ventricular arrhythmias in rats in which mitochondrial KATP channels may be involved.

Cardiac arrhythmias are an important cause of morbidity in infants. Although the spectrum of types of arrhythmia has been reported, there has been no previous population-based study of the incidence of arrhythmias in infancy. Our aim was to define the population incidence of arrhythmia in infants.We based this study on the Northern Region of England with a resident population of 3.1 million and an annual live birth rate of 33,000. We identified all clinically significant arrhythmias in infants in 1991-2010 from the regional cardiac database. All diagnoses were based on analysis of the electrocardiogram. Infants with only the substrate for arrhythmia (such as QT prolongation or ventricular pre-excitation) were excluded.In 20 years, there were 662,698 live births. We identified 162 cases of newly diagnosed arrhythmia of which 22 had associated structural cardiovascular malformations. The incidence of arrhythmia was 24.4 per 100,000 live births. The most common arrhythmia was atrioventricular re-entry tachycardia with an incidence of 16.3 per 100,000. Complete atrioventricular block and atrial flutter both occurred at 2.1 cases per 100,000 live births, and other arrhythmias were rare.This study is the first to report a population incidence of arrhythmia in infants.