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P-wave indices reflect atrial abnormalities contributing to atrial fibrillation (AF). We aimed to assess a comprehensive set of P-wave characteristics for prediction of incident AF in a population-based setting. Malmö Preventative Project (MPP) participants were reexamined in 2002–2006 with electrocardiographic (ECG) and echocardiographic examinations and followed for 5 years. AF-free subjects (n = 983, age 70 ± 5 years, 38% females) with sinus rhythm ECGs were included in the study. ECGs were digitally processed using the Glasgow algorithm. P-wave duration, axis, dispersion, P-terminal force in lead V1 and interatrial block (IAB) were evaluated. ECG risk score combining the morphology, voltage and length of P-wave (MVP score) was calculated. New-onset diagnoses of AF were obtained from nation-wide registers. During follow up, 66 patients (7%) developed AF. After adjustment for age and gender, the independent predictors of AF were abnormal P-wave axis > 75° (HR 1.63 CI95% 1.95–11.03) and MVP score 4 (HR 6.17 CI 95% 1.76–21.64), both correlated with LA area: Person r − 0.146, p < 0.001 and 0.192, p < 0.001 respectively. Advanced IAB (aIAB) with biphasic P-wave morphology in leads III and aVF was the most prevalent variant of aIAB and predicted AF in a univariate model (HR 2.59 CI 95% 1.02–6.58). P-wave frontal axis and MVP score are ECG-based AF predictors in the population-based cohort. Our study provides estimates for prevalence and prognostic importance of different variants of aIAB, providing a support to use biphasic P-wave morphology in lead aVF as the basis for aIAB definition. • The detailed account of different variants of interatrial block (IAB) is provided. • Morphology-voltage-P-wave duration (MVP) score is validated in epidemiologic cohort. • Advanced IAB (aIAB) appears to be associated with left atrial enlargement. • The most prevalent aIAB type is aIAB with biphasic morphology in leads aVF and III. • High MVP score, but not aIAB, independently predicts incident atrial fibrillation. [ABSTRACT FROM AUTHOR]

The ECG diagnosis of LVH is predominantly based on the QRS voltage criteria, i.e. the increased QRS complex amplitude in defined leads. The classical ECG diagnostic paradigm postulates that the increased left ventricular mass generates a stronger electrical field, increasing the leftward and posterior QRS forces. These increased forces are reflected in the augmented QRS amplitude in the corresponding leads. However, the clinical observations document increased QRS amplitude only in the minority of patients with LVH. The low sensitivity of voltage criteria has been repeatedly documented. We discuss possible reasons for this shortcoming and proposal of a new paradigm. [Display omitted] [ABSTRACT FROM AUTHOR]

The present study aimed at testing the hypothesis that atrial fibrillatory rate (AFR) is predictive of sinus rhythm maintenance after electrical cardioversion. The study comprised 32 patients admitted for cardioversion of atrial fibrillation of short duration (mean duration 3.8 ± 7.7 days). AFR was estimated using frequency power spectrum analysis of QRST-cancelled ECG. At six-weeks follow-up 22% of the patients had relapsed to AF. The pre-cardioversion mean AFR of those was 332 ± 64 fpm compared to 378 ± 59 fpm among patients maintaining sinus rhythm (p = 0.12). AFR was not predictive of sinus rhythm maintenance in patients of short duration AF undergoing cardioversion. This is in stark contrast with the earlier reported findings. NCT02112318 (http://www.clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Introduction: A reliable electrocardiographic predictor of ventricular fibrillation (VF) in patients with ST elevation myocardial infarction (STEMI) is lacking so far. Previous experimental/simulation study suggested a terminal T-wave inversion (TTWI) in ischemia-related ECG leads corresponding to anterior infarct localization as an independent predictor of reperfusion VF (rVF). This T-wave characteristic has never been tested as a rVF predictor in clinical settings. The aim of this study was to test if terminal T-wave inversion (TTWI) at admission ECG (before reperfusion) can serve as a predictor of ventricular fibrillation during reperfusion (rVF) in patients with anterior STEMI undergoing primary PCI.Methods and Results: Study population included consecutive patients with anterior infarct localization admitted for primary PCI (n = 181, age 65 [57; 76] years, 66% male). Of those, 14 patients had rVF (rVF group, age 59 [47; 76] years, 64% male) and patients without rVF comprised the No-rVF group (n = 167, age 65 [57; 76] years, 66% male). Association of TTWI with rVF was analyzed using logistic regression analysis adjusted for relevant clinical and electrocardiographic covariates. The prevalence of TTWI in rVF group was 62% comparing to 23% in the No-rVF group, p = 0.005. TTWI was associated with increased risk of rVF (OR 5.51; 95% CI 1.70-17.89; p = 0.004) and remained a significant predictor after adjustment for age, gender, history of MI prior to index admission, VF before reperfusion, Tpeak-Tend, maximal ST elevation, and QRS duration (OR 23.49; 95% CI 3.14-175.91; p = 0.002).Conclusions: The terminal T-wave inversion in anterior leads before PCI independently predicted rVF in patients with anterior MI thus confirming the previous experimental/simulation findings. [ABSTRACT FROM AUTHOR]

Background: Generally considered benign, electrocardiographic (ECG) early repolarization (ER) pattern was claimed to be an indicator of increased susceptibility to ventricular arrhythmias during acute ischemia.Objective: The purpose of this study was to assess in a nonselected population whether ER pattern documented before ST-elevation myocardial infarction (STEMI) is associated with risk of hemodynamically unstable ventricular tachycardia (VT) or ventricular fibrillation (VF) during acute STEMI.Methods: For STEMI patients admitted for primary percutaneous coronary intervention from 2007-2010, the latest ECGs recorded before STEMI were exported in digital format. After excluding ECGs with paced rhythm and QRS duration ≥120 ms, the remaining ECGs were processed using the Glasgow algorithm allowing automatic ER detection. The association between ER pattern and VT/VF during the first 48 hours of STEMI was tested using logistic regression.Results: ECGs recorded before STEMI were available for 1584 patients. Of these patients, 124 did not meet inclusion criteria, leaving 1460 patients available for analysis (age 68 ± 12 years; 67% male). ER pattern was present in 272 patients (18.6%; ER+ group). ER+ and ER- groups did not differ with regard to clinical characteristics. VT/VF during the first 48 hours of STEMI occurred in 19 ER+ (7.0%) and 105 ER- patients (8.8%; P = .398). ER was not associated with any VT/VF (odds ratio [OR] 0.78; 95% confidence interval [CI] 0.47-1.29; P = .324); VT/VF before reperfusion (OR 0.48; 95% CI 0.23-1.001; P = .051); or reperfusion-related VT/VF (OR 1.28; 95% CI 0.55-3.01; P = .569).Conclusion: In a nonselected population of STEMI patients, the ER pattern on ECG recorded before the acute coronary event was not associated with VT/VF during the first 48 hours of STEMI. [ABSTRACT FROM AUTHOR]

Introduction: The relationship between left ventricular (LV) ejection fraction (EF) and LV myocardial scar can identify potentially reversible causes of LV dysfunction. Left bundle branch block (LBBB) alters the electrical and mechanical activation of the LV. We hypothesized that the relationship between LVEF and scar extent is different in LBBB compared to controls.Methods: We compared the relationship between LVEF and scar burden between patients with LBBB and scar (n = 83), and patients with chronic ischemic heart disease and scar but no electrocardiographic conduction abnormality (controls, n = 90), who had undergone cardiovascular magnetic resonance (CMR) imaging at one of three centers. LVEF (%) was measured in CMR cine images. Scar burden was quantified by CMR late gadolinium enhancement (LGE) and expressed as % of LV mass (%LVM). Maximum possible LVEF (LVEFmax) was defined as the function describing the hypotenuse in the LVEF versus myocardial scar extent scatter plot. Dysfunction index was defined as LVEFmax derived from the control cohort minus the measured LVEF.Results: Compared to controls with scar, LBBB with scar had a lower LVEF (median [interquartile range] 27 [19-38] vs 36 [25-50] %, p < 0.001), smaller scar (4 [1-9] vs 11 [6-20] %LVM, p < 0.001), and greater dysfunction index (39 [30-52] vs 21 [12-35] % points, p < 0.001).Conclusions: Among LBBB patients referred for CMR, LVEF is disproportionately reduced in relation to the amount of scar. Dyssynchrony in LBBB may thus impair compensation for loss of contractile myocardium. [ABSTRACT FROM AUTHOR]

Background: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) carries risk of sudden death. We hypothesize that the S-wave angle differentiates ARVD/C with otherwise normal electrocardiograms from controls.Materials and Methods: All patients met Task Force 2010 definite ARVD/C criteria. ARVD/C patients without Task Force depolarization/repolarization criteria (-ECG) were compared to controls. Electrocardiogram measures of QRS duration, corrected QT interval, and measured angle between the upslope and downslope of the S-wave in V2, were assessed.Results: Definite ARVD/C was present in 155 patients (42.7 ± 17.3 years, 68.4%male). -ECG ARVD/C patients (66 patients) were compared to 66 control patients (41.8 ± 17.6 years, 65.2%male). Only the S-wave angle differentiated -ECG ARVD/C patients from controls (<0.001) with AU the ROC curve of 0.77 (95%CI 0.53 to 0.71) and odds ratio of 28.3 (95%CI 6.4 to 125.5).Conclusion: ARVD/C may lead to development of subtle ECG abnormalities distinguishable using the S-wave angle prior to development of 2010 Taskforce ECG criteria. [ABSTRACT FROM AUTHOR]

Aims: We aimed to improve the electrocardiographic 2009 left bundle branch block (LBBB) Selvester QRS score (2009 LBSS) for scar assessment.Methods: We retrospectively identified 325 LBBB patients with available ECG and cardiovascular magnetic resonance imaging (CMR) with late gadolinium enhancement from four centers (142 [44%] with CMR scar). Forty-four semi-automatically measured ECG variables pre-selected based on the 2009 LBSS yielded one multivariable model for scar detection and another for scar quantification.Results: The 2009 LBSS achieved an area under the curve (AUC) of 0.60 (95% confidence interval 0.54-0.66) for scar detection, and R2 = 0.04, p < 0.001, for scar quantification. Multivariable modeling improved scar detection to AUC 0.72 (0.66-0.77) and scar quantification to R2 = 0.21, p < 0.001.Conclusions: The 2009 LBSS detects and quantifies myocardial scar with poor accuracy. Improved models with extensive comparison of ECG and CMR had modest performance, indicating limited room for improvement of the 2009 LBSS. [ABSTRACT FROM AUTHOR]

Introduction: Not only repolarization, but also depolarization ECG indexes reflect the progression of ischemic injury. The aim was to assess the QRS duration and morphology dynamics during the prolonged coronary occlusion and their association with the myocardial area at risk (MaR) and final infarct size (IS).Methods: In pigs, myocardial infarction was induced by inflation of an angioplasty balloon in the left descending artery (LAD), and ECG was continuously recorded. QRS duration was calculated on a beat-to-beat basis during the occlusion period. Single photon emission computed tomography (SPECT) was performed for the assessment of MaR, and IS was assessed by magnetic resonance imaging (MRI).Results: All animals developed an anteroseptal infarction with MaR 40±9% and IS 23±7%. Two peaks of QRS widening were found in all animals: the early peak immediately after LAD occlusion and the late one 17.7±4.1min later. No association was found between MaR and IS and either QRS width or the degree of QRS widening at the early peak. QRS duration on the late peak correlated with both MaR (r=0.61; p=0.007) and IS (r=0.55; p=0.018).Conclusion: The QRS widening at the late peak, but not at the early peak, is associated with the size of myocardial injury, suggesting different underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Revision of the Task Force diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) has increased their sensitivity for the diagnosis of early and familial forms of the disease. The epsilon wave is a major diagnostic criterion in the context of ARVC/D, which, however, remains not quantifiable and therefore may leave room for substantial subjective interpretation.Objective: The purpose of this study was to assess interobserver agreement in epsilon wave definition and epsilon wave importance for ARVC/D diagnosis.Methods: Electrocardiographic (ECG) tracings depicting leads V1, V2, and V3 collected from individuals evaluated for ARVC/D (n = 30) were given to panel members who were asked to respond to the question whether ECG patterns meet epsilon wave definition outlined by the Task Force diagnostic criteria. The prevalence and importance of epsilon waves for ARVC/D diagnosis were assessed in a pooled data set of patients with definite ARVC/D from European and American registries (n = 815).Results: The number of ECG patterns identified as epsilon waves varied from 5 to 18 per reviewer (median 13 per reviewer). A unanimous agreement was reached for only 10 cases (33%), 2 of which qualified as epsilon waves and 8 as non-epsilon waves by all panel members. From a pooled data set, 106 patients reportedly had epsilon waves (13%). In 105 of 106 patients with epsilon waves (99%), exclusion of epsilon waves from the diagnostic score would not affect the "definite" diagnostic category.Conclusion: Interobserver variability in the assessment of epsilon waves is high; however, the impact of epsilon waves on ARVC/D diagnosis is negligibly low. The results urge to exercise caution in the assessment of epsilon waves, especially in patients who would not otherwise meet diagnostic criteria. [ABSTRACT FROM AUTHOR]

The atrioventricular (AV) node plays a fundamental role in patients with atrial fibrillation (AF), acting as a filter to the numerous irregular atrial impulses which bombard the node. A phenomenological approach to better understand AV nodal electrophysiology is to analyze the ventricular response with respect to irregularity. In different cohorts of AF patients, such analysis has been performed with the aim to evaluate the association between ventricular response characteristics and long-term clinical outcome and to determine whether irregularity is affected by rate-control drugs. Another approach to studying AV nodal characteristics is to employ a mathematical model which accounts for the refractory periods of the two AV nodal pathways. With atrial fibrillatory rate and RR intervals as input, the model has been considered for analyzing data during (i) rest and head-up tilt test, (ii) tecadenoson and esmolol, and (iii) rate-control drugs. The present paper provides an overview of our recent work on the characterization and assessment of AV nodal conduction using these two approaches. [ABSTRACT FROM AUTHOR]

Aim: We aimed at assessing changes in AV nodal properties during administration of the beta blockers metoprolol and carvedilol, and the calcium channel blockers diltiazem and verapamil from electrocardiographic data.Methods: Parameters accounting for the functional refractory periods of the slow and fast pathways (aRPs and aRPf) were estimated using atrial fibrillatory rate (AFR) and ventricular response assessed from 15-min ECG segments recorded at baseline and on drug treatment from sixty patients with permanent AF.Results: The results showed that AFR and HR were significantly reduced for all drugs, and that aRPs and aRPf were significantly prolonged in both pathways. The prolongation in aRP was significantly larger for the calcium channel blockers than for the beta blockers.Conclusions: The changes observed in the AV node parameters are in line with the results of previous electrophysiological studies performed in patients during sinus rhythm, therefore supporting the clinical value of the method. [ABSTRACT FROM AUTHOR]

Introduction Severe atrial structural remodeling may reflect irreversible damage of the atrial tissue in patients with atrial fibrillation (AF) and is associated with changes of P-wave duration and morphology. Our aim was to study whether variability of P-wave morphology (PMV) is associated with outcome in patients with AF after circumferential PV isolation (CPVI). Methods and results 70 consecutive patients (aged 60 ± 9 years, 46 men) undergoing CPVI due to symptomatic AF were studied. After cessation of antiarrhythmic therapy, standard 12-lead ECG during sinus rhythm was recorded for 10 min at baseline and transformed to orthogonal leads. Beat-to-beat P-wave morphology was subsequently defined using a pre-defined classification algorithm. The most commonly observed P-wave morphology in a patient was defined as the dominant morphology. PMV was defined as the percentage of P waves with non-dominant morphology in the 10-min sample. At the end of follow-up, 53 of 70 patients had no arrhythmia recurrence. PMV was greater in patients without recurrence (19.5 ± 17.1% vs. 8.2 ± 6.7%, p < 0.001). In the multivariate logistic regression model, PMV ≥ 20% (upper tertile) was the only independent predictor of ablation success (OR = 11.4, 95% CI 1.4–92.1, p = 0.023). A PMV ≥ 20% demonstrated a sensitivity of 41.5%, a specificity of 94.1%, a PPV of 96.7%, and an NPV of 34.0% for free of AF after CPVI. Conclusions We report a significant association between increased PMV and 6-month CPVI success. PMV may help to identify patients with very high likelihood of freedom of AF 6-months after CPVI. [ABSTRACT FROM AUTHOR]

Background: Certain types of the early repolarization phenomenon, previously considered to be benign, have been reported to be associated with ventricular fibrillation (VF), both in population-based studies and in the myocardial infarction (MI) settings. Objective: To analyze whether QRS widening and appearance of a J-wave pattern in experimental MI settings is predictive of VF. Methods: MI was induced in 32 pigs by 40-minute inflation of an angioplasty balloon in the left descending artery, and electrocardiogram was continuously recorded. Multilead QRS boundaries were computed, and QRS duration was calculated on a beat-to-beat basis during the occlusion period for each pig. An association between QRS widening and subsequent VF was studied using receiver operating characteristic curve analysis. Electrocardiograms at maximum QRS duration were reviewed for the presence of a J-wave pattern. Results: Sixteen animals had VF episodes during the occlusion period. Two peaks of QRS widening were found in all animals: the first peak immediately on left descending artery occlusion and the second peak 19.1 ± 4.0 minutes later. The magnitude of changes in the QRS width over time had significant interindividual differences. A QRS widening of ≥28 ms during a 3-minute time window was observed in 14 animals and predicted impending VF (selectivity 80%, specificity 73%, positive predictive value 57%, and negative predictive value 89%; P = .008). In 10 of 14 (71%) pigs, a J-wave pattern appeared at maximal QRS duration. The appearance of a J-wave pattern predicted VF with selectivity 80%, specificity 68%, positive predictive value 53%, and negative predictive value 88% (P = .02). Conclusion: Transient QRS widening, commonly associated with a J-wave pattern, appears to predict impending VF in acute ischemia settings and motivates further clinical studies for monitoring immediate risk of VF in MI. [Copyright &y& Elsevier]

Background In STEMI, grade-3 ischemia (G3) on admission ECG predicts larger infarct size (IS) than grade-2 (G2). We evaluated whether pre-hospital G3 and its temporal behavior are associated with IS and salvage after pPCI. Methods In 401 STEMI patients, pre-hospital and pre-PCI ECGs were classified as G3 or G2. IS was assessed by single-photon emission computed tomography (SPECT) at 30 days. In 245 patients, pre-PCI SPECT was available to determine myocardium at risk (MaR). Results G3 criteria were met by 88, and G2 by 313 patients. G3 was independently associated with IS (p = 0.006). With ST resolution (STR) group as a reference, G2- > G2, G2- > G3 and G3- > G3 were associated with larger IS (B = 4.4, p = 0.004; B = 5.4, p = 0.01; B = 10.2, p < 0.001, respectively), whereas G3- > G2 was not. Salvage was similar between G3 and G2 on pre-hospital ECG if treated early, however lower for G3 when treated later (> 2.5 h); 48% (35-78) vs 62% (40-87); p = 0.04. Conclusion Development or persistence of G3 is associated with larger IS and less salvage, but decreasing grade G3- > G2 was not. [ABSTRACT FROM AUTHOR]

Abstract: Background: Fibro-fatty transformation is believed to be the leading cause of deteriorated atrial conduction; however, any direct assessment in relation to P-wave characteristics is lacking. We sought to assess P-wave morphology (PWM) and duration (PWD) in relation to histology of the atrial myocardium. Objective: Atrial specimens were collected from 11 patients who died from cardiovascular causes (7 men; median age 73years). Methods: Tissue samples were taken at the level of superior and inferior PVs, center of posterior left atrial wall, terminal crest (CT) and Bachmann's bundle (BB) for assessment of fibro-fatty tissue extent. Standard 12-lead ECGs in sinus rhythm recorded during hospital stay were used for manual assessment of P-wave. Partial interatrial block (pIAB) was defined as a prolonged (≥ 120ms) and bimodal P-wave in any lead on 12-lead ECG. Results: The median PWD was 160 (120–200) ms. Fibrosis extent in CT highly correlated to PWD (r=0.914, p<0.001). The combination of fibrosis extent and fatty tissue in BB (16%, range 1%–41%), CT (18%, range 3%–47%) or superior PV (15%, range 6%–24%) correlated to PWD (r=0.627, p=0.039; r=0.795, p=0.003; and r=0.668, p=0.025, respectively). pIAB pattern was observed in 10 subjects; however, it was not associated with either fibrosis or fatty tissue content at any sampling location. Conclusions: Our findings further support causal association between PWD and the extent of structural abnormalities in the atrial myocardium and the major atrial conduction routes. [Copyright &y& Elsevier]

Background: Individual corrected QT interval (QTc) may vary widely among carriers of the same long QT syndrome (LQTS) mutation. Currently, neither the mechanism nor the implications of this variable penetrance are well understood. Objectives: To hypothesize that the assessment of QTc variance in patients with congenital LQTS who carry the same mutation provides incremental prognostic information on the patient-specific QTc. Methods: The study population comprised 1206 patients with LQTS with 95 different mutations and≥5 individuals who carry the same mutation. Multivariate Cox proportional hazards regression analysis was used to assess the effect of mutation-specific standard deviation of QTc (QTcSD) on the risk of cardiac events (comprising syncope, aborted cardiac arrest, and sudden cardiac death) from birth through age 40 years in the total population and by genotype. Results: Assessment of mutation-specific QTcSD showed large differences among carriers of the same mutations (median QTcSD 45 ms). Multivariate analysis showed that each 20 ms increment in QTcSD was associated with a significant 33% (P = .002) increase in the risk of cardiac events after adjustment for the patient-specific QTc duration and the family effect on QTc. The risk associated with QTcSD was pronounced among patients with long QT syndrome type 1 (hazard ratio 1.55 per 20ms increment; P<.001), whereas among patients with long QT syndrome type 2, the risk associated with QTcSD was not statistically significant (hazard ratio 0.99; P = .95; P value for QTcSD-by-genotype interaction = .002). Conclusions: Our findings suggest that mutations with a wider variation in QTc duration are associated with increased risk of cardiac events. These findings appear to be genotype-specific, with a pronounced effect among patients with the long QT syndrome type 1 genotype. [ABSTRACT FROM AUTHOR]

Abstract: Background: T-wave alternans (TWA) is associated with prognosis after myocardial infarction (MI), however its link to the extent of ischemic injury has not been clarified. We analyzed the course of TWA and its relation to myocardial damage in experimental myocardial infarction. Methods: In 21 pigs, infarction was induced by 40-minute long balloon inflation in LAD under continuous 12-lead ECG monitoring. TWA was assessed in a 32-beat sliding window, using periodic component analysis and the Laplacian Likelihood Ratio method. Myocardium at risk (MaR) and infarct size (IS) were evaluated by SPECT and magnetic resonance imaging respectively. Results: TWA appeared at 7.2±4.5minutes of occlusion, reached its maximum at 12.7±6.3 and lasted until 26.5±9.2minutes. The maximal level of TWA was associated with both MaR (r=0.499, p=0.035) and IS (r=0.65, p=0.004). Conclusion: TWA magnitude is associated with both MaR and IS in experiment, which encourages further studies in clinical settings. [Copyright &y& Elsevier]

Abstract: Atrial fibrillatory rate (AFR) can predict outcome of interventions for atrial fibrillation (AF); however, AFR behavior at AF onset in humans is poorly described. We studied AFR during spontaneous AF episodes in patients with lone paroxysmal AF who received implantable loop recorders and had AF episodes of 1 hour or more recorded (n=4). Mean AFR per minute was assessed from continuous implantable loop recorder electrocardiogram using spatiotemporal QRST cancellation and time-frequency analysis. Atrial fibrillatory rate increased from 290±20 to 326±39 fibrillations per minute during the first 3 hours (P <.05) and reached plateau then. Atrial fibrillatory rate beyond the initial 3 hours can, therefore, be considered stable and may be evaluated for prediction of intervention effect. [Copyright &y& Elsevier]

Background: Men and women with type 1 long QT syndrome (LQT1) exhibit time-dependent differences in the risk for cardiac events. Objective: We hypothesized that sex-specific risk for LQT1 is related to the location and function of the disease-causing mutation in the KCNQ1 gene. Methods: The risk for life-threatening cardiac events (comprising aborted cardiac arrest [ACA] or sudden cardiac death [SCD]) from birth through age 40 years was assessed among 1051 individuals with LQT1 (450 men and 601 women) by the location and function of the LQT1-causing mutation (prespecified as mutations in the intracellular domains linking the membrane-spanning segments [ie, S2–S3 and S4–S5 cytoplasmic loops] involved in adrenergic channel regulation vs other mutations). Results: Multivariate analysis showed that during childhood (age group: 0–13 years) men had >2-fold (P < .003) increased risk for ACA/SCD than did women, whereas after the onset of adolescence the risk for ACA/SCD was similar between men and women (hazard ratio = 0.89 [P = .64]). The presence of cytoplasmic-loop mutations was associated with a 2.7-fold (P < .001) increased risk for ACA/SCD among women, but it did not affect the risk among men (hazard ratio 1.37; P = .26). Time-dependent syncope was associated with a more pronounced risk-increase among men than among women (hazard ratio 4.73 [P < .001] and 2.43 [P = .02], respectively), whereas a prolonged corrected QT interval (≥500 ms) was associated with a higher risk among women than among men. Conclusion: Our findings suggest that the combined assessment of clinical and mutation location/functional data can be used to identify sex-specific risk factors for life-threatening events for patients with LQT1. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to assess the association between structural changes in human atria, age, and history of atrial fibrillation (AF). Background: Development of fibrosis in atrial walls is associated with deterioration of atrial conduction and predisposes to AF in experiment. Human data, however, are scarce, and whether fibrosis is a cause or consequence of AF is not known. Methods: Medical records for consecutive autopsies were checked for AF history and duration. Atrial specimens from 30 patients (ages 64 ± 12 years) were collected in 3 equal age-matched groups as patients without AF history, with paroxysmal AF, or with permanent AF. Tissue samples were obtained at the level of superior pulmonary veins, inferior pulmonary veins, center of posterior left atrial wall, terminal crest, and Bachmann''s bundle. Histology sections were assessed for extent of fibrosis, fatty tissues, and inflammatory infiltration at each location. Results: No correlation was observed between age and fibrosis at any location. Fibrosis extent and fatty infiltration were twofold to threefold higher at all locations in patients with history of AF and correlated with lymphomononuclear infiltration. Patients with permanent AF had greater fibrosis extent than did patients with paroxysmal AF. Conclusions: In post-mortem material, structural changes in the atria were not associated with age, but were significantly correlated with presence of AF and its severity. Our findings suggest that age-related changes per se are unlikely to be the sole cause of advanced fibrosis underlying AF. [ABSTRACT FROM AUTHOR]

Abstract: Atrial fibrillation (AF) remains the most common arrhythmia encountered in clinical practice. Electrocardiogram (ECG)-based predictors of clinical outcome, however, have mostly been studied during sinus rhythm, whereas noninvasive risk stratification of patients with AF remains largely unexplored. Advances in ECG signal processing have led to the development of noninvasive methods of atrial fibrillatory rate (AFR) assessment using spatiotemporal QRST cancellation and time frequency analysis that demonstrated its predictive value for the outcome of pharmacologic and catheter-based interventions for AF. Recently, the prognostic value of AFR was evaluated in patients with congestive heart failure and indicated that reduced AFR may be an independent predictor of total and congestive heart failure–related mortality. A high degree of irregularity of the RR intervals during AF and its dependence on the modulation of the atrioventricular conduction rather than sinus node automaticity hampers the use of conventional heart rate variability approach in patients with AF. However, RR irregularity measures that can be applied to short-time ECG recordings appear to be promising predictors of clinical outcome. [Copyright &y& Elsevier]

Background: Men and women with type 2 long QT syndrome (LQT2) exhibit time-dependent differences in the risk for cardiac events. We hypothesized that data regarding the location of the disease-causing mutation in the KCNH2 channel may affect gender-specific risk in LQT2. Objective: This study sought to risk-stratify LQT2 patients for life-threatening cardiac events based on clinical and genetic information. Methods: The risk for life-threatening cardiac events from birth through age 40 years (comprising aborted cardiac arrest [ACA] or sudden cardiac death [SCD]) was assessed among 1,166 LQT2 male (n = 490) and female (n = 676) patients by the location of the LQTS-causing mutation in the KCNH2 channel (prespecified in the primary analysis as pore-loop vs. non–pore-loop). Results: During follow-up, the cumulative probability of life-threatening cardiac events years was significantly higher among LQT2 women (26%) as compared with men (14%; P <.001). Multivariate analysis showed that the risk for life-threatening cardiac events was not significantly different between women with and without pore-loop mutations (hazard ratio 1.20; P =.33). In contrast, men with pore-loop mutations displayed a significant >2-fold higher risk of a first ACA or SCD as compared with those with non–pore-loop mutations (hazard ratio 2.18; P = .01). Consistently, women experienced a high rate of life-threatening events regardless of mutation location (pore-loop: 35%, non–pore-loop: 23%), whereas in men the rate of ACA or SCD was high among those with pore-loop mutations (28%) and relatively low among those with non–pore-loop mutations (8%). Conclusion: Combined assessment of clinical and mutation-specific data can be used for improved risk stratification for life-threatening cardiac events in LQT2. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This study evaluates depolarization changes in acute myocardial ischemia by analysis of QRS slopes. Methods: In 38 patients undergoing elective percutaneous coronary intervention, changes in upward slope between Q and R waves and downward slope between R and S waves (DS) were analyzed. In leads V1 to V3, upward slope of the S wave was additionally analyzed. Ischemia was quantified by myocardial scintigraphy. Also, conventional QRS and ST measures were determined. Results: QRS slope changes correlated significantly with ischemia (for DS: r = 0.71, P < .0001 for extent, and r = 0.73, P < .0001 for severity). Best corresponding correlation for conventional electrocardiogram parameters was the sum of R-wave amplitude change (r = 0.63, P < .0001; r = 0.60, P < .0001) and the sum of ST-segment elevation (r = 0.67, P < .0001; r = 0.73, P < .0001). Prediction of extent and severity of ischemia increased by 12.2% and 7.1% by adding DS to ST. Conclusions: The downward slope between R and S waves correlates with ischemia and could have potential value in risk stratification in acute ischemia in addition to ST-T analysis. [Copyright &y& Elsevier]

Abstract: Introduction: Correlation function analysis applied to endocardial electrograms has earlier been used for analysis of agreement between signals and direction of activation during atrial fibrillation (AF). This study was aimed at evaluating whether preferential activation patterns along the coronary sinus (CS) exist in patients with AF. Methods: Twenty-seven patients (57 ± 10 years old) admitted for electrophysiological (EP) study (10 patients) and/or AF ablation (17 patients) were studied, 8 with permanent and 19 with persistent AF. Unipolar signals were recorded during 60 seconds from a 10-pole CS catheter during AF at baseline (BL) and after isolation of left and right pulmonary veins and after additional lines in the left atrium (LA) (End). Correlation function analysis was applied to signals from each pair of adjacent electrodes, and graphs of cumulated time delay were made to enable interpretation of direction of activation. Results: Correlation between paired signals was highest in the distal and middle parts of CS and lowest in the proximal CS. In 21 patients, correlation values greater than 0.8 between closely spaced electrodes suggested uniform propagation of the fibrillatory waves. In 18 of 21 patients, preferential conduction pattern along CS was seen. Of those, 15 patients had left-to-right conduction, and 3 had right-to-left conduction. During ablation, atrial fibrillation cycle length increased from 184 ± 32 milliseconds at BL to 193 ± 39 milliseconds after pulmonary vein isolation and 215 ± 39 milliseconds at the end of ablation (P = .03, BL vs End). Because of ablation, preferential conduction along CS changed in 4 patients from left to right at BL to simultaneous CS activation or right to left. In 1 of 3 patients with simultaneous activation at BL, the direction changed to right to left. No direction change was observed in any of the 3 patients with right-to-left activation at BL. Conclusions: Atrial activation during AF exhibits a high degree of organization in distal and middle CS. Preferential conduction patterns observed in most patients may indicate either relatively dominant stable reentry circuits in the LA or activation spread from a focal source. The changes in preferential conduction during ablation of AF may reflect modification of AF substrate and indicate persistent right atrial sources not affected by ablation in the LA only. [Copyright &y& Elsevier]

Abstract: Previous studies indicate that the predictive value of atrial fibrillatory rate in patients undergoing cardioversion of atrial fibrillation (AF) of long duration is limited. The present study investigates signal entropy in this setting. Standard 12-lead electrocardiograms (ECGs) were recorded from 66 consecutive patients with AF undergoing cardioversion and sample entropy estimated. Patients were followed for 4 weeks. At follow-up, 59% of the patients had relapsed to AF. The AF signal entropy of these patients before cardioversion was 0.099 ± 0.015, whereas it was 0.093 ± 0.012 among the 41% maintaining sinus rhythm (P = .02). As hypothesized, signal entropy was lower in patients who maintained sinus rhythm 4 weeks after cardioversion than in those who did not. However, the overlap was large, making its clinical value limited. [Copyright &y& Elsevier]

Abstract: Introduction: Structural right atrial abnormalities have been described in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). However, little is known about electrocardiographic signs of atrial involvement in ARVC because no systematic studies have been conducted. Methods: P-wave–triggered signal-averaged orthogonal electrocardiogram from 40 ARVC patients (46 ± 15 years, 16 females) was compared with recordings from age- and sex-matched healthy control subjects for assessment of P-wave duration and morphology. P-wave morphology was classified with regard to the P-wave polarity in leads X, Y, and Z. Results: P-wave duration was longer in patients (135 ± 18 vs 124 ± 12 milliseconds; P = .003). Two typical P-wave morphologies were identified in the controls: positive in X and Y and negative (45%) or biphasic (55%) in Z. In patients with ARVC , typical P waves were seen in only 60%, whereas 15 patients (37%) had atypical P-wave positive in all 3 leads (P < .0001). The presence of atypical P waves in the ARVC group was not associated with the presence of either structural or functional right ventricular abnormality. Conclusions: Patients with ARVC commonly demonstrate deteriorated atrial activation expressed either as prolonged P-wave duration or abnormal P-wave morphology. The P-wave abnormalities were not secondary to right ventricular dilatation. These findings show that atrial involvement is common in ARVC and may represent yet another manifestation of the disease to be considered for inclusion in ARVC diagnostic workup. [Copyright &y& Elsevier]

Abstract: Background: Exacerbation of ST elevation associated with reperfusion has been reported in patients with myocardial infarction. However, the cause of the “reperfusion peak” and relation of its magnitude to the size of myocardial damage has not been explored. The aim of our study was to assess the correlation between the ST-dynamics during reperfusion, the myocardium at risk (MaR), and the infarct size (IS). Methods: Infarction was induced in 15 pigs by a 40-minute-long balloon inflation in the left anterior descending coronary artery. Tetrofosmin Tc 99m was given intravenously after 20 minutes of occlusion, and ex vivo single photon emission computed tomography was performed to assess MaR. Maximal ST elevation in a single lead and maximal sum of ST deviations in 12 leads were measured before, during, and after occlusion from continuous 12-lead electrocardiographic monitoring. A gadolinium-based contrast agent was given intravenously 30 minutes before explantation of the heart. Final IS was estimated using ex vivo cardiac magnetic resonance imaging. Results: All pigs developed an anteroseptal infarct with MaR = 42% ± 9% and IS = 26% ± 7% of left ventricle. In all pigs, reperfusion was accompanied by transitory exacerbation of ST elevation that measured 1300 ± 500 μV as maximum in a single lead compared with 570 ± 220 μV at the end of occlusion (P < .001). The transitory exacerbation of ST elevation exceeded the maximal ST elevation during occlusion (920 ± 420 μV, P < .05). The ST elevation resolved by the end of the reperfusion period (90 ± 30 μV, P < .001). Exacerbation of ST elevation after reperfusion correlated with the final IS (r = 0.64, P = .025 for maximal ST elevation in a single lead and r = 0.80, P = .002 for sum of ST deviations) but not with MaR (r = 0.43, P = .17 for maximal ST elevation in a single lead and r = 0.49, P = .11 for sum of ST deviations). The maximal ST elevation in a single lead and the sum of ST deviations during occlusion did not correlate with either MaR or final IS. Conclusion: In the experiment, exacerbation of ST elevation is common during restoration of blood flow in the occluded coronary artery. The magnitude of the exacerbation of ST elevation after reperfusion in experimentally induced myocardial infarction in pigs is associated with infarct size but not with MaR. [Copyright &y& Elsevier]

Abstract: Introduction: Twelve-lead electrocardiogram (ECG) is used to screen for hypertrophic cardiomyopathy (HCM), but up to 25% of HCM patients do not have distinctly abnormal ECGs, whereas up to 5% to 15% of healthy athletes do. We hypothesized that an approximately 5-minute resting advanced 12-lead ECG test (“A-ECG score”) could detect HCM with greater sensitivity than pooled conventional ECG criteria and distinguish healthy athletes from HCM with greater specificity. Materials and methods: Five-minute 12-lead ECGs were obtained from 56 HCM patients, 56 age/sex-matched healthy controls, and 69 younger endurance-trained athletes. Electrocardiograms were analyzed using recently suggested pooled conventional ECG criteria and also A-ECG scoring techniques that considered results from multiple advanced and conventional ECG parameters. Results: Compared with pooled criteria from the strictly conventional ECG, an A-ECG logistic score incorporating results from just 3 advanced ECG parameters (spatial QRS-T angle, unexplained portion of QT variability, and T-wave principal component analysis ratio) increased the sensitivity of ECG for identifying HCM from 89% (78%-96%) to 98% (89%-100%; P = .025), while increasing specificity from 90% (83%-94%) to 95% (92%-99%; P = .020). Conclusions: Resting 12-lead A-ECG scores that are simultaneously more sensitive than pooled conventional ECG criteria for detecting HCM and more specific for distinguishing healthy athletes and other healthy controls from HCM can be constructed. Pending further prospective validation, such scores may lead to improved ECG-based screening for HCM. [Copyright &y& Elsevier]

Background: Technical developments in the management of atrial arrhythmias revived interest into the detailed knowledge of atrial anatomy. The atrial septum (AS), known for its complex structure, has been particularly difficult to study, and our knowledge of the muscular bundles providing routes for intra-atrial and interatrial conduction within the AS remains limited. Objective: The purpose of this study was to describe myocardial arrangement within the AS and adjacent parts of atrial walls for delineation of possible substrates for interatrial and intra-atrial conduction. Methods: Human heart specimens from 84 postmortem studies were studied using conventional morphometric assessment, blunt dissection, and light microscopy of serial histological sections of AS. Results: Interatrial muscular connections are present anteriorly, posteriorly between right pulmonary veins, and inferiorly between the coronary sinus and the right inferior pulmonary vein. The inferior connections can be more prominent than the Bachmann bundle. Atrial musculature in the fossa ovalis consists of muscular bands isolated by fatty tissue from the endocardium of the right and left atrium. They are arranged along the anterior–posterior axis and have connections with left atrial myocardium. Myocardial fascicles in the posterior–inferior and superior portions of the muscular rim of fossa ovalis originate on the right atrial side and can be traced toward the atrioventricular node. Conclusion: The general myocardial arrangement in the AS and adjacent regions of atrial walls are important for understanding propagation of atrial activation for selection of the optimal treatment strategy. [Copyright &y& Elsevier]