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Aims: Short QT syndrome type 1 (SQT1) is a genetic channelopathy caused by gain-of-function variants in human-ether-a-go-go (HERG) underlying the rapid delayed-rectifier K+ current (IKr), leading to QT-shortening, ventricular arrhythmias, and sudden cardiac death. Data on efficient pharmacotherapy for SQT1 are scarce. In patients with primary carnitine-deficiency, acquired-short QT syndrome (SQTS) has been observed and rescued by carnitine supplementation. Here, we assessed whether carnitine exerts direct beneficial (prolonging) effects on cardiac repolarization in genetic SQTS., Methods and Results: Adult wild-type (WT) and transgenic SQT1 rabbits (HERG-N588K, gain of IKr) were used. In vivo electrocardiograms (ECGs), ex vivo monophasic action potentials (APs) in Langendorff-perfused hearts, and cellular ventricular APs and ion currents were assessed at baseline and during L-Carnitine/C16-Carnitine-perfusion. Two-dimensional computer simulations were performed to assess re-entry-based ventricular tachycardia-inducibility. L-Carnitine/C16-Carnitine prolonged QT-intervals in WT and SQT1, leading to QT-normalization in SQT1. Similarly, monophasic and cellular AP duration (APD) was prolonged by L-Carnitine/C16-Carnitine in WT and SQT1. As underlying mechanisms, we identified acute effects on the main repolarizing ion currents: IKr-steady, which is pathologically increased in SQT1, was reduced by L-Carnitine/C16-Carnitine and deactivation kinetics were accelerated. Moreover, L-Carnitine/C16-Carnitine decreased IKs-steady and IK1. In silico modelling identified IKr changes as the main factor for L-Carnitine/C16-Carnitine-induced APD-prolongation. 2D simulations revealed increased sustained re-entry-based arrhythmia formation in SQT1 compared to WT, which was decreased to the WT-level when adding carnitine-induced ion current changes., Conclusion: L-Carnitine/C16-Carnitine prolong/normalize QT and whole-heart/cellular APD in SQT1 rabbits. These beneficial effects are mediated by acute effects on IKr. L-Carnitine may serve as a potential future QT-normalizing, anti-arrhythmic therapy in SQT1., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Mutations are known to cause perturbations in essential functional features of integral membrane proteins, including ion channels. Even restricted or point mutations can result in substantially changed properties of ion currents. The additive effect of these alterations for a specific ion channel can result in significantly changed properties of the action potential (AP). Both AP shortening and AP prolongation can result from known mutations, and the consequences can be life-threatening. Here, we present a computational method for identifying new drugs utilizing combinations of existing drugs. Based on the knowledge of theoretical effects of existing drugs on individual ion currents, our aim is to compute optimal combinations that can 'repair' the mutant AP waveforms so that the baseline AP-properties are restored. More specifically, we compute optimal, combined, drug concentrations such that the waveforms of the transmembrane potential and the cytosolic calcium concentration of the mutant cardiomyocytes (CMs) becomes as similar as possible to their wild type counterparts after the drug has been applied. In order to demonstrate the utility of this method, we address the question of computing an optimal drug for the short QT syndrome type 1 (SQT1). For the SQT1 mutation N588K, there are available data sets that describe the effect of various drugs on the mutated K+ channel. These published findings are the basis for our computational analysis which can identify optimal compounds in the sense that the AP of the mutant CMs resembles essential biomarkers of the wild type CMs. Using recently developed insights regarding electrophysiological properties among myocytes from different species, we compute optimal drug combinations for hiPSC-CMs, rabbit ventricular CMs and adult human ventricular CMs with the SQT1 mutation. Since the 'composition' of ion channels that form the AP is different for the three types of myocytes under consideration, so is the composition of the optimal drug., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: KJ, AE, and AT have financial relationships with Organos Inc., and the company may benefit from commercialization of the results of this research. In addition, WG serve as a Consultant for InCarda Ltd. concerning their efforts to develop new pharmaceutical approaches for atrial fibrillation.

Short QT (SQT) syndrome is a genetic cardiac disorder characterized by an abbreviated QT interval of the patient's electrocardiogram. The syndrome is associated with increased risk of arrhythmia and sudden cardiac death and can arise from a number of ion channel mutations. Cardiomyocytes derived from induced pluripotent stem cells generated from SQT patients (SQT hiPSC-CMs) provide promising platforms for testing pharmacological treatments directly in human cardiac cells exhibiting mutations specific for the syndrome. However, a difficulty is posed by the relative immaturity of hiPSC-CMs, with the possibility that drug effects observed in SQT hiPSC-CMs could be very different from the corresponding drug effect in vivo. In this paper, we apply a multistep computational procedure for translating measured drug effects from these cells to human QT response. This process first detects drug effects on individual ion channels based on measurements of SQT hiPSC-CMs and then uses these results to estimate the drug effects on ventricular action potentials and QT intervals of adult SQT patients. We find that the procedure is able to identify IC50 values in line with measured values for the four drugs quinidine, ivabradine, ajmaline and mexiletine. In addition, the predicted effect of quinidine on the adult QT interval is in good agreement with measured effects of quinidine for adult patients. Consequently, the computational procedure appears to be a useful tool for helping predicting adult drug responses from pure in vitro measurements of patient derived cell lines., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: KJ, SW and AT have financial relationships with Organos Inc, and the company may benefit from commercialization of the results of this research.

Brugada syndrome and early repolarization syndrome are both classified as J-wave syndromes, with a similar mechanism of arrhythmogenesis and with the same basis for genesis of the characteristic electrocardiographic features. The Brugada syndrome is now considered a conduction disorder based on subtle structural abnormalities in the right ventricular outflow tract. Recent evidence suggests structural substrate in patients with the early repolarization syndrome as well. We propose a unifying mechanism based on these structural abnormalities explaining both arrhythmogenesis and the electrocardiographic changes. In addition, we speculate that, with increasing technical advances in imaging techniques and their spatial resolution, these syndromes will be reclassified as structural heart diseases or cardiomyopathies.

Background: Short QT syndrome is a rare, inherited channelopathy associated with sudden cardiac arrest (SCA) but the characteristics and prognosis of short QT interval (SQTI) in Korean patients remain unclear. This study aimed to determine the clinical characteristics and outcomes of SQTI in a Korean population., Methods: Consecutive patients with SQTI from January 1999 to March 2019 in three university hospitals in South Korea were recruited. SQTI was defined as a Bazett's formula-corrected QT interval (QTc) ≤ 340 ms in serial electrocardiograms. Age- and sex-matched patients with a normal QTc and without overt cardiovascular disease were included in a 1:4 ratio. Clinical and ECG features and outcomes were compared between patients with and without SQTI., Results: 34 patients with SQTI [age, 23.5 (21-30.5) years; 31 male] were followed up for 4.8 (2.0-7.8) years. Early repolarization, tall T wave, and U wave were significantly more frequent in patients with SQTI than in those without SQTI. QT dispersion [44.0 (28.0-73.0) vs. 20.0 (12.0-35.0) ms, P < 0.001] was significantly wider and heart rate [52.0 (47.0-58.0) vs. 70.0 (62.3-84.0)/min, P < 0.001] was significantly slower in patients with SQTI than in those without. Atrial fibrillation (AF, 11.8% vs. 2.2%, P = 0.030) and ventricular arrhythmia (VA)/SCA (8.7% vs. 0%, P = 0.007) were significantly more frequent in patients with SQTI than in those without. SQTI was significantly associated with AF [odds ratio, 5.911; 95% confidence interval, 1.257-27.808; P = 0.025] and VA/SCA., Conclusions: In this subset of Korean population, SQTI was associated with AF and VA/SCA.

Short QT syndrome (SQTS) predisposes afflicted patients to sudden cardiac death. Until now, only one drug-quinidine-has been shown to be effective in patients with SQTS type 1(SQTS1). The objective of this study was to use human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with SQTS1 to search for potentially effective drugs for the treatment of SQTS1 patients. Patch clamp and single-cell contraction measurements were employed to assess drug effects. Ivabradine, mexiletine, and ajmaline but not flecainide, ranolazine, or amiodarone prolonged the action potential duration (APD) in hiPSC-CMs from an SQTS1 patient. Ivabradine, ajmaline, and mexiletine inhibited KCNH2 channel currents significantly, which may underlie their APD-prolonging effects. Under proarrhythmic epinephrine stimulation in spontaneously beating SQTS1 hiPSC-CMs, ivabradine, mexiletine, and ajmaline but not flecainide reduced the epinephrine-induced arrhythmic events. The results demonstrate that ivabradine, ajmaline, and mexiletine may be candidate drugs for preventing tachyarrhythmias in SQTS1 patients., (© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.)

Aims: Short-QT syndrome 1 (SQT1) is an inherited channelopathy with accelerated repolarization due to gain-of-function in HERG/IKr. Patients develop atrial fibrillation, ventricular tachycardia (VT), and sudden cardiac death with pronounced inter-individual variability in phenotype. We generated and characterized transgenic SQT1 rabbits and investigated electrical remodelling., Methods and Results: Transgenic rabbits were generated by oocyte-microinjection of β-myosin-heavy-chain-promoter-KCNH2/HERG-N588K constructs. Short-QT syndrome 1 and wild type (WT) littermates were subjected to in vivo ECG, electrophysiological studies, magnetic resonance imaging, and ex vivo action potential (AP) measurements. Electrical remodelling was assessed using patch clamp, real-time PCR, and western blot. We generated three SQT1 founders. QT interval was shorter and QT/RR slope was shallower in SQT1 than in WT (QT, 147.8 ± 2 ms vs. 166.4 ± 3, P < 0.0001). Atrial and ventricular refractoriness and AP duration were shortened in SQT1 (vAPD90, 118.6 ± 5 ms vs. 154.4 ± 2, P < 0.0001). Ventricular tachycardia/fibrillation (VT/VF) inducibility was increased in SQT1. Systolic function was unaltered but diastolic relaxation was enhanced in SQT1. IKr-steady was increased with impaired inactivation in SQT1, while IKr-tail was reduced. Quinidine prolonged/normalized QT and action potential duration (APD) in SQT1 rabbits by reducing IKr. Diverse electrical remodelling was observed: in SQT1, IK1 was decreased-partially reversing the phenotype-while a small increase in IKs may partly contribute to an accentuation of the phenotype., Conclusion: Short-QT syndrome 1 rabbits mimic the human disease phenotype on all levels with shortened QT/APD and increased VT/VF-inducibility and show similar beneficial responses to quinidine, indicating their value for elucidation of arrhythmogenic mechanisms and identification of novel anti-arrhythmic strategies., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Cardiomyopathy, a leading cause of death worldwide, is etiologically and phenotypically heterogeneous and is caused by a combination of genetic and non-genetic factors. Major genomic determinants of dilated cardiomyopathy (DCM) are titin truncating mutations and lamin A/C mutations. Patients with these two genotypes show critically different phenotypes, including penetrance, coexistence with a conduction system abnormality, cardiac prognosis, and treatment response. The transcriptomic and epigenomic characteristics of DCM include activation of the DNA damage response, metabolic reprogramming, and dedifferentiation. The proteomic and metabolomic signatures of the DCM heart include a rigorous dependency for free fatty acids, activation of the stress response, and metabolic reprogramming. Proteomic and metabolomic analyses of blood show a distinct immune response and an unexpected link with pathology-specific microbiota in DCM. The direct integration of multi-omics data will not only elucidate inter-omics associations but also enable omics-based patient stratification, which will lead to a deeper understanding of cardiomyopathy and the development of precision medicine in cardiology., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Cardiac sympathetic denervation (CSD) is a surgical option for patients with life-threatening ventricular arrhythmias. Previously described cohorts included populations in which CSD was performed for primary and secondary prevention. We report the efficacy of CSD as adjunct therapy in children with medically refractory life-threatening arrhythmias., Materials and Methods: Retrospective review of patients undergoing thoracoscopic CSD at one institution between January 2008 and July 2017. Patient demographics, indications, procedural details, complications, length of stay, and effectiveness were evaluated., Results: Ten thoracoscopic CSD procedures were performed in 8 patients. Mean age was 8.2 years (8 days-19 years); mean weight was 32.6 kg (2.7-57 kg); and 50% were female. Four had long QT syndrome, 3 catecholaminergic polymorphic ventricular tachycardia, and 1 short QT syndrome. All patients had at least two (2 to >40) episodes of resuscitated ventricular arrhythmia and were maximized on medical therapy. Six patients had implantable cardioverter-defibrillators (ICD) with a mean of 11.9 appropriate discharges (1-40) before CSD. All patients underwent left CSD; 2 subsequently required right CSD. Four of the 6 ICD patients experienced dramatic improvement (total 48 ICD discharges pre-CSD; 3 post-CSD). Two patients noncompliant with medical therapy had no significant improvement (24 ICD discharges pre-CSD; 23 post-CSD) and also underwent right CSD, again with no improvement (23 discharges pre-right CSD; 28 post-right CSD)., Conclusions: Thoracoscopic CSD can be safely performed in the neonate and pediatric populations. When utilized with medication therapy, CSD is an effective adjunct in reducing ICD discharges and arrhythmias.

Background: Short QT syndrome (SQTS), a disorder associated with characteristic ECG QT-segment abbreviation, predisposes affected patients to sudden cardiac death. Despite some progress in assessing the organ-level pathophysiology and genetic changes of the disorder, the understanding of the human cellular phenotype and discovering of an optimal therapy has lagged because of a lack of appropriate human cellular models of the disorder. The objective of this study was to establish a cellular model of SQTS using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs)., Methods and Results: This study recruited 1 patient with short QT syndrome type 1 carrying a mutation (N588K) in KCNH2 as well as 2 healthy control subjects. We generated hiPSCs from their skin fibroblasts, and differentiated hiPSCs into cardiomyocytes (hiPSC-CMs) for physiological and pharmacological studies. The hiPSC-CMs from the patient showed increased rapidly activating delayed rectifier potassium channel current (I K r ) density and shortened action potential duration compared with healthy control hiPSC-CMs. Furthermore, they demonstrated abnormal calcium transients and rhythmic activities. Carbachol increased the arrhythmic events in SQTS but not in control cells. Gene and protein expression profiling showed increased KCNH2 expression in SQTS cells. Quinidine but not sotalol or metoprolol prolonged the action potential duration and abolished arrhythmic activity induced by carbachol., Conclusions: Patient-specific hiPSC-CMs are able to recapitulate single-cell phenotype features of SQTS and provide novel opportunities to further elucidate the cellular disease mechanism and test drug effects., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Short QT syndrome (SQTS) is a genetic arrhythmogenic disease that can cause malignant arrhythmia and sudden cardiac death. The current therapies for SQTS have application restrictions. We previously found that Mg· (NH 2 CH 2 CH 2 SO 3 )2· H 2 O, a taurine-magnesium coordination compound (TMCC) exerted anti-arrhythmic effects with low toxicity. In this study we established 3 different models to assess the potential anti-arrhythmic effects of TMCC on type 2 short QT syndrome (SQT2). In Langendorff guinea pig-perfused hearts, perfusion of pinacidil (20 μmol/L) significantly shortened the QT interval and QTpeak and increased rTp-Te (P<0.05 vs control). Subsequently, perfusion of TMCC (1-4 mmol/L) dose-dependently increased the QT interval and QTpeak (P<0.01 vs pinacidil). TMCC perfusion also reversed the rTp-Te value to the normal range. In guinea pig ventricular myocytes, perfusion of trapidil (1 mmol/L) significantly shortened the action potential duration at 50% (APD 50 ) and 90% repolarization (APD 90 ), which was significantly reversed by TMCC (0.01-1 mmol/L, P<0.05 vs trapidil). In HEK293 cells that stably expressed the outward delayed rectifier potassium channels (I Ks ), perfusion of TMCC (0.01-1 mmol/L) dose-dependently inhibited the IKs current with an IC 50 value of 201.1 μmol/L. The present study provides evidence that TMCC can extend the repolarization period and inhibit the repolarizing current, I Ks , thereby representing a therapeutic candidate for ventricular arrhythmia in SQT2.

Objectives: The goal of this study was to evaluate whether prolonged ventricular conduction (paced QRS) and repolarization (paced QTc) times observed during ventricular stimulation predict ventricular arrhythmic events and death., Background: Abnormal ventricular conduction and repolarization can predispose patients to ventricular arrhythmias., Methods: Consecutive patients with left ventricular dysfunction (ejection fraction <50%) undergoing electrophysiology studies from January 2002 until May 2014 were identified at Mayo Clinic (Rochester, Minnesota). Patients were followed up until December 2014 for occurrence of ventricular arrhythmias and death., Results: Among the 501 patients included (mean age 65 years; mean left ventricular ejection fraction 33.1%), longer paced ventricular conduction was associated with longer baseline QRS duration, longer QT interval, and lower ejection fraction. On multivariable analysis, longer paced QRS duration was associated with higher risk of ventricular arrhythmia (hazard ratio [HR]: 1.11 per 10-ms increase; 95% confidence interval [CI]: 1.07 to 1.16; p < 0.001) and all-cause death or arrhythmia (HR: 1.09; 95% CI: 1.09 to 1.13; p < 0.001). A paced QRS duration >190 ms was associated with a 3.6 times higher risk of ventricular arrhythmia (HR: 3.6; 95% CI: 2.35 to 5.53; p < 0.001) and a 2.1 times higher risk of death or arrhythmia (HR: 2.12; 95% CI: 1.53 to 2.95; p < 0.001), independent of left ventricular function or baseline QRS duration. Longer QTc interval during ventricular pacing was associated with a higher risk of ventricular arrhythmia (HR: 1.03 per 10-ms increase; 95% CI: 1.02 to 1.12; p < 0.001) independent of paced QRS duration., Conclusions: Longer paced QRS duration and paced QTc interval predict ventricular arrhythmias in patients with cardiomyopathy. Ventricular conduction and repolarization prolongation during right ventricular pacing can determine the risk of ventricular arrhythmias., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Gain of function in mutations, D172N and E299V, of Kir2.1 will induce type III short QT syndrome. In our previous work, we had identified that a mixture of traditional Chinese medicine, styrax, is a blocker of Kir2.1. Here, we determined a monomer, hydrocinnamic acid (HA), as the effective component from 18 compounds of styrax. Our data show that HA can inhibit the currents of Kir2.1 channel in both excised inside-out and whole-cell patch with the IC 50 of 5.21 ± 1.02 and 10.08 ± 0.46 mM, respectively. The time course of HA blockage and washout are 2.3 ± 0.6 and 10.5 ± 2.6 s in the excised inside-out patch. Moreover, HA can also abolish the currents of D172N and E299V with the IC 50 of 6.66 ± 0.57 and 5.81 ± 1.10 mM for D172N and E299V, respectively. Molecular docking results determine that HA binds with Kir2.1 at K182, K185, and K188, which are phosphatidylinositol 4,5-bisphosphate (PIP 2 ) binding residues. Our results indicate that HA competes with PIP 2 to bind with Kir2.1 and inhibits the currents.

Objective: Short QT syndrome (SQTS) is an inherited cardiac channelopathy, but at present little information is available on its pharmacological treatment. SQT3 variant (linked to the inward rectifier potassium current I K1 ) of SQTS, results from a gain-of-function mutation (Kir2.1 D172N) in the KCNJ2-encoded channels, which is associated with ventricular fibrillation (VF). Using biophysically-detailed human ventricular computer models, this study investigated the potential effects of quinidine, disopyramide, and E-4031 on SQT3., Approach: The ten Tusscher et al model of human ventricular myocyte action potential (AP) was modified to recapitulate the changes in I K1 due to heterozygous and homozygous forms of the D172N mutation. Wild-type (WT) and mutant WT-D172N and D172N formulations were incorporated into one-dimensional (1D) and 2D tissue models with transmural heterogeneities. Effects of drugs on channel-blocking activity were modelled using half-maximal inhibitory concentration (IC 50 ) and Hill coefficient (nH) values. Effects of drugs on AP duration (APD), effective refractory period (ERP) and QT interval of pseudo-ECGs were quantified, and both temporal and spatial vulnerability to re-entry was measured. Re-entry was simulated in the 2D ventricular tissue., Main Results: At the single cell level, the drugs quinidine, disopyramide, and E-4031 prolonged APD at 90% repolarization (APD 90 ), and decreased maximal transmural voltage heterogeneity (δV); this caused the decreased transmural dispersion of APD 90 . Quinidine prolonged the QT interval and decreased the T-wave amplitude. Furthermore, quinidine increased ERP and reduced temporal vulnerability and increased spatial vulnerability, resulting in a reduced susceptibility to arrhythmogenesis in SQT3. In the 2D tissue, quinidine was effective in terminating and preventing re-entry associated with the heterozygous D172N condition. Quinidine exhibited significantly better therapeutic effects on SQT3 than disopyramide and E-4031., Significance: This study substantiates a causal link between quinidine and QT interval prolongation in SQT3 Kir2.1 mutations and highlights possible pharmacological agent quinidine for treating SQT3 patients.

Background: One of the principal tasks of an emergency physician is identifying potentially life-threatening conditions in the undifferentiated patient; cardiac dysrhythmia is an example of such a condition. A systematic approach to a patient with atypical dysrhythmia enables proper identification of such-life threatening conditions., Case Report: We describe a 31-year-old man presenting to the emergency department with an undifferentiated dysrhythmia after naloxone reversal of an opiate overdose. A systematic approach to the electrocardiogram led to the rare diagnosis of Wolff-Parkinson-White (WPW) alternans. We review the differential diagnosis of this dysrhythmia and the initial evaluation of a patient with the WPW pattern present on their electrocardiogram. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should be prepared to use a systematic approach to an undifferentiated dysrhythmia to identify potentially life-threatening conditions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The use of electroanatomical mapping can facilitate the identification of the ideal cryoablation site by providing a three-dimensional map of the earliest activation site. Combined use of the cryoablation technology with electroanatomical mapping can further increase the precision and safety of the procedure by applying test applications at a lower energy level.

Background: Atrial arrhythmias are frequently described in congenital heart disease., Objectives: To provide a surgical perspective of anti-arrhythmic procedures and strategic approaches., Methods: Discussion of the history of anti-arrhythmic treatments in congenital heart disease., Results: Before the advent of the Maze procedure (first published in 1991), surgery mainly focused on patients with Wolff-Parkinson-White syndrome and also on arrhythmias in Ebstein's malformation. Atrial septal defects (ASD) subsequently received more attention, i.e., in terms of atrial arrhythmia in the natural prognosis and the surgically modified course and in terms of surgical versus transcatheter approaches. Based on the background of various atrial arrhythmia mechanisms of ASD, several surgical procedures have been reported, ranging from the bilateral full Maze procedure to simple modification of right atriotomy. The so-called right atrial Maze procedure occupies a special position from the viewpoint of cardiology in acquired heart disease, especially in cases of frequently occurring right heart failure. In hearts with more complex structural abnormalities, a detailed understanding of the conditions to improve overall surgical outcome and develop future "anti-arrhythmic" strategies is necessary., Conclusions: It is important to precisely specify factors in the individual cases, not only morphological diversity but also technical and strategic variations and their consequences. A variety of anti-arrhythmic surgical procedures are currently available. How and when to use which procedure requires professional insight and cautious clinical decision-making.

Background: Epsilon waves and other depolarization abnormalities in the right precordial leads are thought to represent delayed activation of the right ventricular outflow tract in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). However, no study has directly correlated cardiac electrical activation with the surface ECG findings in ARVD/C., Methods and Results: Thirty ARVD/C patients (mean age 32.7 ± 11.2 years, 16 men) underwent endocardial and epicardial electroanatomical activation mapping in sinus rhythm. Twelve-lead ECGs were classified into 5 patterns: (1) normal QRS (11 patients); (2) terminal activation delay (TAD) (3 patients); (3) incomplete right bundle branch block (IRBBB) (5 patients); (4) epsilon wave (5 patients); (5) complete right bundle branch block (CRBBB) (6 patients). Timing of local ventricular activation and extent of scar was then correlated with surface QRS. Earliest endocardial and epicardial RV activation occurred on the mid anteroseptal wall in all patients despite the CRBBB pattern on ECG. Total RV activation times increased from normal QRS to prolonged TAD, IRBBB, epsilon wave, and CRBBB, respectively (103.9 ± 5.6, 116.3 ± 6.5, 117.8 ± 2.7, 146.4 ± 16.3, and 154.3 ± 6.3, respectively, P < 0.05). The total epicardial scar area (cm(2) ) was similar among the different ECG patterns. Median endocardial scar burden was significantly higher in patients with epsilon waves even compared with patients with CRBBB (34.3 vs. 11.3 cm(2) , P < 0.01). Timing of epsilon wave corresponded to activation of the subtricuspid region in all patients., Conclusion: We found that epsilon waves are often associated with severe conduction delay and extensive endocardial scarring in addition to epicardial disease. The timing of epsilon waves on surface ECG correlated with electrical activation of the sub-tricuspid region., (© 2016 Wiley Periodicals, Inc.)

Background: Idiopathic ventricular arrhythmias (VAs) originating from the pulmonary sinus cusp (PSC) have not been sufficiently clarified., Objectives: The goal of this study was to investigate the prevalence, electrocardiographic characteristics, mapping, and ablation of idiopathic VAs arising from the PSC., Methods: Data were analyzed from 218 patients undergoing successful endocardial ablation of idiopathic VAs with a left bundle branch block morphology and inferior axis deviation., Results: Twenty-four patients had VAs originating from the PSC. In the first 7 patients, initial ablation performed in the right ventricular outflow tract failed to abolish the clinical VAs but produced a small change in the QRS morphology in 3 patients. In all 24 patients, the earliest activation was eventually identified in the PSC, at which a sharp potential was observed preceding the QRS complex onset by 28.2 ± 2.9 ms. The successful ablation site was in the right cusp (RC) in 10 patients (42%), the left cusp (LC) in 8 (33%), and the anterior cusp (AC) in 6 (25%). Electrocardiographic analysis showed that RC-VAs had significantly larger R-wave amplitude in lead I and a smaller aVL/aVR ratio of Q-wave amplitude compared with AC-VAs and LC-VAs, respectively. The R-wave amplitude in inferior leads was smaller in VAs localized in the RC than in the LC but did not differ between VAs from the AC and LC., Conclusions: VAs arising from the PSC are not uncommon, and RC-VAs have unique electrocardiographic characteristics. These VAs can be successfully ablated within the PSC., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Cardiac disorders caused by sofosbuvir are liable to be worsened by concomitant use of one of the many drugs that provoke cardiac arrhythmia.

This study investigated the prevalence and type of electrocardiography (ECG) abnormalities, and their possible association with the clinical/radiological findings in 118 consecutive patients with non-traumatic, non-neoplastic intracerebral hemorrhage (ICH). ECG frequently demonstrates abnormalities in patients with ischemic stroke and subarachnoid hemorrhage, but little is known of ECG changes in ICH patients. Clinical and radiological information was retrospectively reviewed. ECG recordings that were obtained within 24 hours of the initial hemorrhage were analyzed. Sixty-six patients (56%) had one or more ECG abnormalities. The most frequent was ST depression (24%), followed by left ventricular hypertrophy (20%), corrected QT interval (QTc) prolongation (19%), and T wave inversion (19%). The logistic regression analysis demonstrated the following: insular involvement was an independent predictive factor of ST depression (p<0.001; odds ratio OR 10.18; 95% confidence interval [CI] 2.84-36.57); insular involvement (p<0.001; OR 23.98; 95% CI 4.91-117.11) and presence of intraventricular hemorrhage (p<0.001; OR 8.72; 95% CI 2.69-28.29) were independent predictive factors of QTc prolongation; deep hematoma location (p<0.001; OR 19.12; 95% CI 3.82-95.81) and hematoma volume >30 ml (p=0.001; OR 6.58; 95% CI 2.11-20.46) were independent predictive factors of T wave inversion. We demonstrate associations between ECG abnormalities and detailed characteristics of ICH., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Atrial pacing during radiofrequency (RF) deliveries is a technique to facilitate rapid recognition of impaired atrioventricular (AV) conduction during slow pathway ablation of AV nodal reentrant tachycardia. The objective of our study was to report this technique in the catheter ablation of para-Hisian arrhythmias., Methods: The study included a total of 48 patients who underwent ablation of para-Hisian arrhythmias including accessory pathways (APs), atrial tachycardias (ATs), and ventricular arrhythmias (VAs) in 6, 9, and 33 patients, respectively., Results: AT was successfully eliminated in all cases without any accelerated junctional rhythm (JR) occurring. JR appeared during RF deliveries in 20 patients (3 with APs, 17 with VAs). In 11 of 20 patients, RF deliveries were terminated when JR appeared and restarted during atrial pacing at a faster rate than the JR. No transient complete AV block was observed in the 11 patients, however it occurred in 1 of the remaining 9 without atrial pacing (p=0.25). Small His bundle potentials were recorded at the effective ablation site before the RF delivery in 11 (55%) patients. No patients had any AV conduction disturbances at the end of and after the procedure. APs were successfully eliminated in 2 of 3 patients. VAs were completely and partially eliminated in 10 and 4 of 17 patients, respectively., Conclusions: Atrial pacing during RF applications might be helpful to avoid AV conduction disturbances during catheter ablation of APs close to the His bundle and idiopathic VAs originating in the vicinity of the His bundle., (Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Electric left ventricular lead position, assessed by the electric delay from the beginning of the QRS complex to the local LV electrogram (QLV), was found in previous studies to be a strong predictor of short-term response to cardiac resynchronization therapy. We hypothesized that suboptimum electric position of the left ventricular lead is associated with an excess of heart failure events and mortality., Methods and Results: We analyzed the clinical outcome of patients with left bundle branch block or intraventricular conduction delay treated with cardiac resynchronization therapy at our institution during 9 years. Baseline clinical characteristics, QLV/QRS duration (QLV ratio) at cardiac resynchronization therapy implant, and data about heart failure hospitalization and mode of death were collected in 329 patients who were followed for a period of 3.3±1.9 years. Of them, 83 were hospitalized for heart failure and 83 died. Event rates for all-cause mortality, cardiac mortality, noncardiac mortality, heart failure mortality, and sudden death were 25.2%, 14.9%, 10.3%, 12.2%, and 2.1%, respectively. Patients with a QLV ratio ≤0.70 had significantly worse event-free survival for all study end points--hazard ratio, 1.6; 95% confidence interval, 1.0 to 2.4; P=0.05 for heart failure hospitalization; hazard ratio, 2.9; 95% confidence interval, 1.6 to 5.5; P=0.001 for heart failure mortality; hazard ratio, 1.8; 95% confidence interval, 1.1 to 2.7; P=0.01 for cardiac mortality; and hazard ratio, 2.1; 95% confidence interval, 1.2 to 3.7; P=0.01 for all-cause mortality. In multivariable analysis, QLV ratio ≤0.70 remained associated with all study end points., Conclusions: Electric left ventricular lead position in cardiac resynchronization therapy patients was a significant predictor of heart failure hospitalization and mortality., (© 2015 American Heart Association, Inc.)

Introduction: A population-level relative risk assessment for comorbidities associated with myotonic dystrophy has not been performed., Methods: In this study we utilized the Utah Population Database to identify patients with myotonic dystrophy in Utah according to ICD-9 coding. Comorbidity cases listed in the medical record were compared with those of the Utah population., Results: Individuals with myotonic dystrophy were found to possess an increased risk of central and obstructive sleep apnea, hypothyroidism, and intellectual disability. The risk of cardiac conduction disorder is 60 times the population risk., Conclusions: This study provides a population-level relative risk assessment of comorbidities in myotonic dystrophy. This allows for improved counseling of patients regarding these increased risks., (© 2015 Wiley Periodicals, Inc.)

Cardiac arrhythmias are often associated with mutations in SCN5A the gene that encodes the cardiac paralogue of the voltage-gated sodium channel, NaV 1.5. The NaV 1.5 mutants R1193Q and E1784K give rise to both long QT and Brugada syndromes. Various environmental factors, including temperature, may unmask arrhythmia. We sought to determine whether temperature might be an arrhythmogenic trigger in these two mixed syndrome mutants. Whole-cell patch clamp was used to measure the biophysical properties of NaV 1.5 WT, E1784K and R1193Q mutants. Recordings were performed using Chinese hamster ovary (CHOk1) cells transiently transfected with the NaV 1.5 α subunit (WT, E1784K, or R1193Q), β1 subunit, and eGFP. The channels' voltage-dependent and kinetic properties were measured at three different temperatures: 10ºC, 22ºC, and 34ºC. The E1784K mutant is more thermosensitive than either WT or R1193Q channels. When temperature is elevated from 22°C to 34°C, there is a greater increase in late INa and use-dependent inactivation in E1784K than in WT or R1193Q. However, when temperature is lowered to 10°C, the two mutants show a decrease in channel availability. Action potential modelling using Q10 fit values, extrapolated to physiological and febrile temperatures, show a larger transmural voltage gradient in E1784K compared to R1193Q and WT with hyperthermia. The E1784K mutant is more thermosensitive than WT or R1193Q channels. This enhanced thermosensitivity may be a mechanism for arrhythmogenesis in patients with E1784K sodium channels., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)

Flexible electronics are the next generation of sensors for mobile health and implantation. Zebrafish (Danio rerio) is an emergent strategy for pre-clinical drug development and toxicity testing. To address the confounding effects from sedation of fish and removal from the aquatic habitat for micro-electrocardiogram (µECG) measurements, we developed waterproof and wearable sensors to uncover the circadian variation in heart rate (HR) and heart rate variability (HRV) (Massin et al., 2000). The parylene-C based ECG sensor consisted of an ultra-soft silicone integrated jacket designed to wrap around the fish during swimming. The Young's modulus of this silicone jacket matched with the fish surface, and an extended parylene cable connected the underwater chest electrodes with the out-of water electronics. In addition, embedded micro-glass spheres in the silicone effectively reduced the effective density of the jacket to ~1 g cm(-3). These innovations enabled physiological ECG telemetry in the fish's natural habitat without the need for sedation. Furthermore, a set of non-linear signal processing techniques filtered out the breathing and electromagnetic artifacts from the recorded signals. We observed a reduction in mean HR and an increase in HRV over 24h at 10 dpa, accompanied by QT prolongation as well as diurnal variations, followed by normalization in mean HR and QT intervals at 26 days post ventricular amputation (dpa). We revealed Amiodarone-mediated QTc prolongation, HR reduction and HRV increase otherwise masked by sedation. The novel features of the flexible silicon jacket for µECG telemetry unraveled the biological clock and normalization of QT intervals at 26 dpa, providing the first evidence of new physiological phenomena during cardiac injury and repair as well as cardiac drug-mediated aberrant rhythms. Thus, the light weight and waterproof design holds promise to advance the next generation of mobile health and drug discovery., (Published by Elsevier B.V.)

Background: Atrial fibrillation (AF) is the most common arrhythmia in humans, yet; treatment has remained sub-optimal due to poor understanding of the underlying mechanisms. Cardiac alternans precede AF episodes, suggesting an important arrhythmia substrate. Recently, we demonstrated ventricular SERCA2a overexpression suppresses cardiac alternans and arrhythmias. Therefore, we hypothesized that atrial SERCA2a overexpression will decrease cardiac alternans and arrhythmias., Methods: Adult rat isolated atrial myocytes where divided into three treatment groups 1) Control, 2) SERCA2a overexpression (Ad.SERCA2a) and 3) SERCA2a inhibition (Thapsigargin, 1μm). Intracellular Ca2+ was measured using Indo-1AM and Ca2+ alternans (Ca-ALT) was induced with a standard ramp pacing protocol., Results: As predicted, SR Ca2+ reuptake was enhanced with SERCA2a overexpression (p< 0.05) and reduced with SERCA2a inhibition (p<0.05). Surprisingly, there was no difference in susceptibility to Ca-ALT with either SERCA2a overexpression or inhibition when compared to controls (p = 0.73). In contrast, SERCA2a overexpression resulted in increased premature SR Ca2+ (SCR) release compared to control myocytes (28% and 0%, p < 0.05) and concomitant increase in SR Ca2+ load (p<0.05). Based on these observations we tested in-vivo atrial arrhythmia inducibility in control and Ad.SERCA2a animals using an esophageal atrial burst pacing protocol. There were no inducible atrial arrhythmias in Ad.GFP (n = 4) animals though 20% of Ad.SERCA2a (n = 5) animals had inducible atrial arrhythmias (p = 0.20)., Conclusions: Our findings suggest that unlike the ventricle, SERCA2a is not a key regulator of cardiac alternans in the atrium. Importantly, SERCA2a overexpression in atrial myocytes can increase SCR, which may be arrhythmogenic.

Background: Contact force (CF) is a major determinant of lesion size and transmurality and has the potential to improve efficacy of atrial fibrillation ablation. This study sought to evaluate the safety and effectiveness of a novel irrigated radiofrequency ablation catheter that measures real-time CF in the treatment of patients with paroxysmal atrial fibrillation., Methods and Results: A total of 300 patients with symptomatic, drug-refractory, paroxysmal atrial fibrillation were enrolled in a prospective, multicenter, randomized, controlled trial and randomized to radiofrequency ablation with either a novel CF-sensing catheter or a non-CF catheter (control). The primary effectiveness end point consisted of acute electrical isolation of all pulmonary veins and freedom from recurrent symptomatic atrial arrhythmia off all antiarrhythmic drugs at 12 months. The primary safety end point included device-related serious adverse events. End points were powered to show noninferiority. All pulmonary veins were isolated in both groups. Effectiveness was achieved in 67.8% and 69.4% of subjects in the CF and control arms, respectively (absolute difference, -1.6%; lower limit of 1-sided 95% confidence interval, -10.7%; P=0.0073 for noninferiority). When the CF arm was stratified into optimal CF (≥90% ablations with ≥10 g) and nonoptimal CF groups, effectiveness was achieved in 75.9% versus 58.1%, respectively (P=0.018). The primary safety end point occurred in 1.97% and 1.40% of CF patients and control subjects, respectively (absolute difference, 0.57%; upper limit of 1-sided 95% confidence interval, 3.61%; P=0.0004 for noninferiority)., Conclusions: The CF ablation catheter met the primary safety and effectiveness end points. Additionally, optimal CF was associated with improved effectiveness., Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT01278953., (© 2015 American Heart Association, Inc.)

Background: The French military population is a young and athletic population with a high prevalence of early repolarization patterns (ERP) compared to the general population. Screening of military officers at risk of sudden death (SD) is a priority in military medical expertise. The aim of our study was to evaluate the prevalence of ERP and its evolution over a period of 5 years in a specific asymptomatic population, free of heart disease and cardiovascular risk factors., Methods: From March to December 2008, we prospectively collected the electrocardiograms (ECGs) of military officers enlisted into the submarine forces of France. For 5 years (until 2012), the military officers included in the study underwent a clinical examination twice per year. A new ECG was carried out 5 years after the initial one., Results: A total of 250 male subjects were included (mean age 22.87 ± 0.5 years). The prevalence of ERP was 19.2%. The most common appearance was an elevation of a slurring type J point (31/48 or 64.5%) in inferolateral leads (18/48 or 37.8%). After 5 years, the prevalence of ERP was identical to that of the previous period (19.2%) with no change in appearance, distribution, and amplitude in 47 subjects (97.9%). Repolarization changed in two patients (one occurrence of ERP and one disappearance). During the 5 years of follow-up, the subjects remained asymptomatic, Conclusion: ERP is common in our population of young, athletic, and asymptomatic military officers and changes little in 5 years., (© 2014 Wiley Periodicals, Inc.)

The authors investigated trends in the Croatian primary Percutaneous Coronary Intervention (pPCI) Network results among three consecutive time intervals (2005-2007, first phase; 2008-2009, second phase; and 2010-2011, third phase). Data on 5650 patients with acute myocardial infarction with ST-elevation (STEMI) transferred or directly admitted and treated with pPCI in 11 Croatian PCI centers during the study period were collected and analyzed. The number of patients with acute STEMI treated with pPCI per year rose continuously during the study period (581 vs. 1272 vs. 1949 patients/year). The patient risk profile worsened during the study period: age (60 vs. 61 vs. 63 years; p<0.01), anterior myocardial wall involvement (43% vs. 44% vs. 51%; p<0.01), shock rate (7% vs. 9% vs. 11%; p<0.05), and percentage of transferred patients (42% vs. 36% vs. 46%; p<0.01). While the door-to-balloon time shortened (108 vs. 98 vs. 75 min; p<0.01), the symptom onset-to-door time increased (130 vs. 175 vs. 195 min; p<0.01), but without statistically significant influence on the total ischemic time. Multivariate log-linear analysis eliminated influence of a higher risk profile on the results of treatment and yielded no statistically significant changes in final TIMI 3 flow (Thrombolysis In Myocardial Infarction 3), in-hospital mortality, and six-month mortality rate, but revealed a significant increase in the rate of angina pectoris (12 vs. 22 vs. 36%; p<0.01) and other major adverse cardiovascular events (MACE; 6 vs. 23 vs. 14%; p<0.01) during follow up. In conclusion, the Croatian pPCI Network continuously ensures very good results of STEMI treatment in this economically less developed European country despite worsening of the risk profile in treated patients and opening of new, less experienced PCI centers. The higher percentage of MACE over time could be explained by changes in the pPCI strategy introduced over time (the culprit lesion only) and higher availability of PCI centers for additional PCI after acute STEMI. However, there is room for improvement, especially in reducing prehospital delay.

Background: High-risk patients with Brugada syndrome (BrS) have inherent late potential (LP) fluctuations that might be explained by autonomic activity, electrolyte abnormality, and body temperature changes. However, the correlation between postural changes and LP determinates remains unknown., Methods: Forty patients with BrS (38 men, 43.9 ± 13.5 years) and 15 controls (15 men, 42.4 ± 11.2 years) were enrolled. LP variations were investigated at five body positions using high-resolution ambulatory monitoring electrocardiography (HR-ambulatory ECG). The HR-ambulatory ECG was recorded for 3 hours and LP parameters (fQRSd, LAS40, and RMS40) were obtained for at least 15 minutes in each at the supine, left and right lateral decubitus, and prone and sitting positions., Results: Determinate LP in the BrS group was significantly abnormal in all positions. Among the five body positions, positive LP were much more frequent in the supine and left and right lateral decubitus positions than in the prone and sitting positions and normalized in the last two positions in patients with BrS. RMS40 variance by postural change was significantly larger in the coved group than in the saddle back group. Determinate LP improved in the sitting position compared to the supine position in the coved group., Conclusions: Positive LP findings normalized in the sitting position in patients in the coved BrS group with a resuscitation history, suggesting that depolarization instability might be related to the risk of fatal ventricular arrhythmia. Posture-induced LP variance should be examined using HR-ambulatory ECG analysis in patients with BrS., (© 2014 Wiley Periodicals, Inc.)

Background: Early repolarization (ER) and acute ST segment elevation myocardial infarction (STEMI) are sharing the pathophysiology of J wave syndromes. It is speculated that early ventricular arrhythmias (VAs) during STEMI may be predisposed by ER. Our aim was to study the association between ER pattern and risk of VAs during acute STEMI., Methods: The study included 102 male patients with acute STEMI who were divided into two groups: cases and controls. Cases included 52 patients with sustained VAs during the first 48 hours from the onset of STEMI, while controls included 50 patients with no VAs. On 12-lead surface electrocardiogram, ER was defined as ≥ 1 mm elevation of J point in at least two inferior or lateral leads with or without ST segment elevation., Results: Mean age was 48.44 ± 10.08 years and mean left ventricular ejection fraction (LVEF) was 42.25 ± 11.1%. ER pattern was more frequent in cases than controls (29 vs 14 patients, P = 0.008). Notched J wave (P = 0.0007) and horizontal ST segment (P = 0.033) were more frequent in cases than controls. On adjusted regression model, LVEF (OR: 0.95, 95% CI: 0.91-0.99, P = 0.015) and ER (OR: 3.39, 95% CI: 1.41-8.12, P = 0.006) could predict VAs, while QTc interval (P = 0.24) and QTd (P = 0.86) did not have predictive effect. Inferior/inferolateral and global ER pattern (P = 0.044 and 0.031 respectively), notched J wave (P = 0.001), increasing J wave amplitude (P = 0.042), and ST segment elevation (P = 0.001) were associated with a higher risk of VAs., Conclusions: ER is associated with increased risk of VAs in the setting of acute STEMI., (© 2014 Wiley Periodicals, Inc.)

Background: The study of atrial conduction defects associated with the onset of paroxysmal atrial fibrillation (PAF) can be addressed by analyzing the P wave from the surface electrocardiogram (ECG). Traditionally, signal-averaged ECGs have been mostly used for this purpose. However, this alternative hinders the possibility to quantify every single P wave, its variability over time, as well as to obtain complimentary and evolving information about the arrhythmia. This work analyzes the time progression of several time and frequency P wave features as potential indicators of atrial conduction variability several hours preceding the onset of PAF., Methods: The longest sinus rhythm interval from 24-hour Holter recordings of 46 PAF patients was selected. Next, the 2 hours before the onset of PAF were extracted and divided into two 1-hour periods. Every single P wave was automatically delineated and characterized by 16 time and frequency metrics, such as its duration, absolute energy in several frequency bands and high-to-low-frequency energy ratios. Finally, the P wave variability over each 1-hour period was estimated from the 16 features making use of a least-squares linear fitting. As a reference, the same parameters were also estimated from a set of 1-hour ECG segments randomly chosen from a control group of 53 healthy subjects age-, gender-, and heart rate-matched., Results: All the analyzed metrics provided an increasing P wave variability trend as the onset of PAF approximated, being P wave duration and P wave high-frequency energy the most significant individual metrics. The linear fitting slope α associated with P wave duration was (2.48 ± 1.98)×10(-2) for healthy subjects, (23.8 ± 14.1)×10(-2) for ECG segments far from PAF and for (81.8 ± 48.7)×10(-2) ECG segments close to PAF p = 6.96×10(-22) . Similarly, the P wave high-frequency energy linear fitting slope was (2.42 ± 4.97)×10(-9) , (54.2 ± 107.1)×10(-9) and (274.2 ± 566.1)×10(-9) , respectively (p = 2.85×10(-20) ). A univariate discriminant analysis provided that both P wave duration and P wave high-frequency energy could discern among the three ECG sets with diagnostic ability around 80%, which was improved up to 88% by combining these metrics in a multivariate discriminant analysis., Conclusion: Alterations in atrial conduction can be successfully quantified several hours before the onset of PAF by estimating variability over time of several time and frequency P wave features., (© 2014 Wiley Periodicals, Inc.)

A woman (49 years) with Chagas' disease showed: ECG, right bundle-branch block and left anterior-superior fascicular block; V1 has unusual R > R', and elevated ST segment from V2 to V6 . Additional imaging revealed concomitant HCM and Chagas, which is uncommon. Overlapping of ECG findings can be explained by this rare association of diseases., (© 2014 Wiley Periodicals, Inc.)

Controversy has followed the groundbreaking and cornerstone paper of Haïssaguerre et al. Much of this controversy has been due to the use of the term "early repolarization pattern" and possible waveform morphologies on the standard 12-lead ECG ( it is 10 second strip) that could predict who will manifest the malignant arrhythmogenic syndrome described by Haïssaguerre et al. The standard ECG definition of early repolarization pattern (ERP) or early repolarization variant (ERV) since then has changed its clinical meaning for a surface electrocardiographic waveform from benign to malignant. The new definition of ERP/ERV contains only J wave but ST-segment elevation is no more obligatory. In the old definition, early repolarization pattern (ERP) or early repolarization variant (ERV) 3 is a well-recognized idiopathic electrocardiographic phenomenon considered to be present when at least two adjacent precordial leads show elevation of the ST segment, with values equal or higher than 1 mm. In the new electrocardiographic ERP concept, the ST segment may or may not be elevated and can be up-sloping, horizontal or down-sloping while in the old ERP/ERV concept it must be elevated at least 1 mm in at least two adjacent leads and the variant is characterized by a diffuse elevation of the ST segment of upper concavity, ending in a positive T wave of V2 to V4 or V5 and prominent J wave and ST-segment elevation predominantly in left precordial leads. The phenomenon constitutes a normal variant; it is almost a rule in athletes (present in 89% of the cases in this universe)., (© 2015 Wiley Periodicals, Inc.)