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This study assesses the incidence of sudden death and classifies the causes of death following radiofrequency ablation of the atrioventricular (AV) junction. We studied 220 patients with paroxysmal (n = 105) or chronic (n = 115) atrial fibrillation (AF) and a mean age of 64 +/- 12 years. These patients were followed 31 +/- 15 months after radiofrequency ablation of the AV junction and pacemaker implantation. In 86 patients, structural heart disease was identified before the procedure. All patients were traced via the Swedish National Civic Registry and Cause of Death Registry. The cause-of-death was classified according to data from death certificates, autopsy protocols, and medical records. Thirty-one patients (mean age 69 +/- 11 years, 16 men) died 15 +/- 15 months (range 0.2 to 60) after the procedure. There were 6 sudden unexplained deaths, 14 cardiovascular deaths, and 11 deaths from noncardiovascular causes. Eleven patients, all with structural heart disease, died suddenly out of hospital 16 +/- 16 months (range 0.2 to 42) after the procedure. In 6 of these there was no obvious cause of death. Three of these 6 patients underwent autopsy, which showed extensive coronary artery disease (n = 1), severe heart failure (n = 1) and cardiac hypertrophy and dilation (n = 1). The remaining 3 all had depressed left ventricular systolic function and a history of congestive heart failure. Five of the patients who died suddenly from cardiovascular causes had autopsies that revealed acute myocardial infarction (n = 4) and massive pulmonary embolism (n = 1). [ABSTRACT FROM AUTHOR]

Left ventricular (LV) hypertrophy is associated with a substantial risk for malignant arrhythmias and sudden death. The effects of antihypertensive therapy on QT dispersion, which reflects cardiac repolarization heterogeneity, in relation to changes in LV mass has not been well studied. Repeat echocardiography and QT measurements (standard 12-lead electrocardiograms) were performed in hypertensive patients with LV hypertrophy, who were randomized double-blind to receive the angiotensin II type 1-receptor blocker irbesartan (n = 44) or the beta(1)-receptor blocker atenolol (n = 48) for 48 weeks, and in 37 matched hypertensive control subjects without LV hypertrophy. LV mass index was related to QT dispersion (r = 0.34, p <0.001). The reduction in LV mass was greater using irbesartan than using atenolol (-27 +/- 28 vs -15 +/- 21 g/m(2) at 48 weeks, p = 0.021), with similar reductions in blood pressure. Irbesartan decreased QT dispersion (from 56 +/- 24 ms to 45 +/- 20 ms at 48 weeks; p <0.001) and QTc dispersion (from 57 +/- 24 to 44 +/- 19 ms at 48 weeks; p <0.001). In contrast, atenolol had minor effects. The decreases in QT and QTc dispersions were greater using irbesartan than using atenolol (p = 0.001 and p = 0.011, respectively); the same results were found when changes in LV mass, blood pressure, and heart rate were also included in multivariate analyses. Thus, heterogeneity of ventricular repolarization is related to the degree of LV hypertrophy. Irbesartan, but not atenolol, reduces QT and QTc dispersions independent of changes in LV mass, blood pressure, or heart rate, and thus seems to induce structural and electrical remodeling in a direction that could decrease the risk of fatal events in hypertensive patients. [ABSTRACT FROM AUTHOR]

Women are more susceptible to the development of Torsades de Pointes ventricular tachycardia and have a longer heart rate-corrected QT interval than men. A causal role for estrogen has been implicated. The purpose of this study was to investigate if hormone replacement therapy (HRT) resulted in any changes in noninvasive depolarization and repolarization measurements, and to study their relation to circulating concentrations of sex hormones. Sixty postmenopausal women with cardiovascular disease (mean age 59 +/- 7 years; range 44 to 75) were randomized to receive oral conjugated estrogens, transdermal estradiol-17-beta (both with addition of progestins), or placebo. QRS, QT, and JT intervals and their dispersion on 12-lead electrocardiograms were analyzed at baseline, and after 6 and 12 treatment cycles of HRT. Blood samples for analyses of serum concentration of estrogens and androgens were obtained on the same occasions. Neither mean RR, QT, QTc, JT, and JTc intervals, nor QT and JT dispersion changed during treatment. There was a significant inverse relation between the mean JTc interval and the serum concentration of estradiol-17-beta, independent of age, testosterone levels, and abdominal obesity. There was also a significant inverse relation between the change in androstenedione levels and the change in QT interval (Spearman -0.35, p = 0.028) or JT interval (Spearman -0.41, p = 0.009) at 6 treatment cycles compared with baseline. In conclusion, treatment with oral conjugated estrogens or transdermal estradiol-17-beta combined with progestins did not alter depolarization or repolarization measurements. However, the inverse relation between repolarization and androgens fits with an effect of androgens on repolarization in postmenopausal women. [ABSTRACT FROM AUTHOR]

Episodes of ventricular fibrillation with subsequent intracardiac, and to a lesser extent, external defibrillation give rise to a statistically significant increase in S-troponin T, S-CK-MB(mass) and S-myoglobin indicative of a minor myocardial injury or dysfunction. In contrast, no such signs were observed after external direct-current conversion of atrial fibrillation using high energies, or after pace-terminated ventricular tachycardia. [ABSTRACT FROM AUTHOR]

Background: Data on long-term effects of catheter ablation vs antiarrhythmic drugs (AADs) on health-related quality of life (HRQoL) and atrial fibrillation (AF) burden are limited., Objective: The study aimed to assess long-term HRQoL and rhythm data in patients with symptomatic AF., Methods: The 75 patients who underwent ablation and 74 receiving AAD in the Catheter Ablation compared with Pharmacological Therapy for Atrial Fibrillation trial were followed for 48 months. The General Health subscale of the 36-Item Short-Form Health Survey, time to first AF episode ≥1 hour, and AF burden, recorded by implantable cardiac monitors, were compared., Results: One hundred forty-seven patients completed follow-up, with 7 crossovers in the ablation group and 34 crossovers in the AAD group. General Health improved by ablation from a median of 62 points at baseline to 79.2 points at follow-up (P < .001) and by AAD from a median of 67 to 77 points (P < .001), without treatment differences (P = .77). Time to first AF episode ≥1 hour was longer (median 257 days in the ablation group vs 180 days in the AAD group; P = .025). The cumulative AF burden during follow-up was lower in the ablation group (median 0.3%; interquartile range [IQR] 0%-1.4%) than in the AAD group (1.6%; IQR 0.1%-11.0%) (P = .01). The cumulative reduction in AF burden compared with baseline was greater in the ablation group (median -89.5%; IQR -98.4% to -51.3%) than in the AAD group (-52.7%; IQR -92.6% to 263.6%); P < .001)., Conclusion: HRQoL improvement at long-term did not differ between ablation and AAD groups despite a larger reduction in AF burden after ablation. The results should be interpreted in the light of a high crossover rate in the AAD group., Competing Interests: Disclosures All authors have declared no conflicts of interest., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Abnormal QRS-T angles are prognostic markers for cardiovascular deaths including sudden cardiac death. They occur in ∼5-6% of population-based cohorts but in ∼20% of patients with diabetes. The mechanistic background, electrical activation and/or recovery disturbances, is not known and the topic of this study., Methods: Applying Frank vectorcardiography (VCG) and simultaneously recorded scalar 12‑lead ECG, electrical activation and recovery of abnormal QRS-T angles were studied in 311 participants (5.4%) from a population-based cohort of 5796 women and men in the main Swedish CArdio-Pulmonary bio-Imaging Study (SCAPIS) in Gothenburg. Cut-off values for the peak and mean QRS-T angles were > 124° and > 119°, based on the >95th percentile among all 1080 participants in the pilot SCAPIS and reference values for normal directions (Q1-Q3) from 319 apparently healthy (30%) of them., Results: Of 311 cases 17% had known cardiac disease. Deviations of QRS and QRSarea-vectors from reference limits (90%) were significantly more common than deviations of T- and Tarea-vectors (65%). Standard ECG signs suggested pathophysiology in 20%; left bundle branch block (LBBB) and voltage criteria for left ventricular hypertrophy being most frequent (9-10%) each. Sub-group analysis of the 30 with LBBB showed very large variability in vector directions., Conclusions: Our observations provide mechanistic insights about abnormal QRS-T angles of potential value for future prognostic and interventional studies. The results also have potential implications for LBB area pacing and the approach to left ventricular hypertrophy., Competing Interests: Declaration of competing interest There are no disclosures to be made for any of the authors in relation to this work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors have nothing to disclose.

Congenital long QT syndrome (LQTS) carries an increased risk for syncope and sudden death. QT prolongation promotes ventricular extrasystoles, which, in the presence of an arrhythmia substrate, might trigger ventricular tachycardia degenerating into fibrillation. Increased electrical heterogeneity (dispersion) is the suggested arrhythmia substrate in LQTS. In the most common subtype LQT1, physical exercise predisposes for arrhythmia and spatiotemporal dispersion was therefore studied in this context. Thirty-seven patients (57% on β-blockers) and 37 healthy controls (mean age, 31 vs. 35; range, 6-68 vs. 6-72 yr) performed an exercise test. Frank vectorcardiography was used to assess spatiotemporal dispersion as T ampl , T area , the ventricular gradient (VG), and the T peak-end interval from 10-s signal averages before and 7 ± 2 min after exercise; during exercise too much signal disturbance excluded analysis. Baseline and maximum heart rates as well as estimated exercise intensity were similar, but heart rate recovery was slower in patients. At baseline, QT and heart rate-corrected QT (QT cB ) were significantly longer in patients (as expected), whereas dispersion parameters were numerically larger in controls. After exercise, QT peakcB and T peak-endcB increased significantly more in patients (18 ± 23 vs. 7 ± 10 ms and 12 ± 17 vs. 2 ± 6 ms; P < 0.001 and P < 0.01). There was, however, no difference in the change in T ampl , T area , and VG between groups. In conclusion, although temporal dispersion of repolarization increased significantly more after exercise in patients with LQT1, there were no signs of exercise-induced increase in global dispersion of action potential duration and morphology. The arrhythmia substrate/mechanism in LQT1 warrants further study. NEW & NOTEWORTHY Physical activity increases the risk for life-threatening arrhythmias in LQTS type 1 (LQT1). The arrhythmia substrate is presumably altered electrical heterogeneity (a.k.a. dispersion). Spatiotemporal dispersion parameters were therefore compared before and after exercise in patients versus healthy controls using Frank vectorcardiography, a novelty. Physical exercise prolonged the time between the earliest and latest complete repolarization in patients versus controls, but did not increase parameters reflecting global dispersion of action potential duration and morphology, another novelty.

Objectives: Cardiopulmonary bypass (CPB) management may potentially play a role in the development of new-onset atrial fibrillation (AF) after cardiac surgery. The aim of this study was to explore this potential association., Methods: Patients who underwent coronary artery bypass grafting and/or valvular surgery during 2016-2020 were included in an observational single-centre study. Data collected from the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry and a local CPB database were merged. Associations between individual CPB variables (CPB and aortic clamp times, arterial and central venous pressure, mixed venous oxygen saturation, blood flow index, bladder temperature and haematocrit) and new-onset AF were analysed using multivariable logistic regression models adjusted for patient characteristics, comorbidities and surgical procedure., Results: Out of 1999 patients, 758 (37.9%) developed new-onset AF. Patients with new-onset postoperative AF were older, had a higher incidence of previous stroke, worse renal function and higher EuroSCORE II and CHA2DS2-VASc scores and more often underwent valve surgery. Longer CPB time [adjusted odds ratio 1.05 per 10 min (95% confidence interval 1.01-1.08); P = 0.008] and higher flow index [adjusted odds ratio 1.21 per 0.2 l/m2 (95% confidence interval 1.02-1.42); P = 0.026] were associated with an increased risk for new-onset AF, while the other variables were not. A sensitivity analysis only including patients with isolated coronary artery bypass grafting supported the primary analyses., Conclusions: CPB management following current guideline recommendations appears to have minor or no influence on the risk of developing new-onset AF after cardiac surgery., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objectives: Data on prognostic implications of new-onset postoperative atrial fibrillation (POAF) after surgical aortic valve replacement (SAVR) is limited. We sought to explore associations between POAF, early initiated oral anticoagulation (OAC) and long-term outcome after SAVR and combined SAVR + coronary artery bypass grafting (CABG)., Methods: This is a retrospective, population-based study including all isolated SAVR (n = 7038) and combined SAVR and CABG patients (n = 3854) without a history of preoperative atrial fibrillation (AF) in Sweden 2007-2017. Individual patient data were merged from 4 nationwide registries. Inverse probability of treatment weighting-adjusted Cox regression models were employed separately in SAVR and SAVR + CABG patients. The median follow-up time was 4.7 years (range 0-10 years)., Results: POAF occurred in 44.5% and 50.7% of SAVR and SAVR + CABG patients, respectively. In SAVR patients, POAF was associated with increased long-term risk of death [adjusted hazard ratio (aHR) 1.21 (95% confidence interval 1.06-1.37)], ischaemic stroke [aHR 1.32 (1.08-1.59)], any thromboembolism, heart failure hospitalization and recurrent AF. In SAVR + CABG, POAF was associated with death [aHR 1.31 (1.14-1.51)], recurrent AF and heart failure, but not with ischaemic stroke [aHR 1.04 (0.84-1.29)] or thromboembolism. OAC was dispensed within 30 days after discharge to 67.0% and 65.9%, respectively, of SAVR and SAVR + CABG patients with POAF. Early initiated OAC was not associated with reduced risk of death, ischaemic stroke or thromboembolism in any group of patients., Conclusions: POAF after SAVR is associated with an increased risk of long-term mortality and morbidity. Further studies are warranted to clarify the role of OAC in SAVR patients with POAF., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The association between type 2 diabetes (T2D) and the development of cardiac arrhythmias and conduction disturbances has not been extensively studied. Arrhythmia was defined as atrial fibrillation and flutter (AF/AFl), ventricular tachycardia (VT) and ventricular fibrillation (VF), and conduction abnormality as sinus node disease (SND), atrioventricular (AV) block or pacemaker implantation, and intraventricular conduction blocks (IVCB). Incidence rates and Cox regression were used to compare outcomes, and to assess optimal levels for cardiometabolic risk factors and risk associated with multifactorial risk factor control (i.e., HbA1c, LDL-C, systolic blood pressure (SBP), BMI and eGFR), between patients with versus without T2D. The analyses included data from 617,000 patients with T2D and 2,303,391 matched controls. Patients with diabetes and the general population demonstrated a gradual increase in rates for cardiac conduction abnormalities and virtually all age-groups for AF/AFI showed increased incidence during follow-up. For patients with versus without T2D, risks for cardiac arrhythmias were higher, including for AF/AFl (HR 1.17, 95% CI 1.16-1.18), the composite of SND, AV-block or pacemaker implantation (HR 1.40, 95% CI 1.37-1.43), IVCB (HR 1.23, 95% CI 1.18-1.28) and VT/VF (HR 1.08, 95% CI 1.04-1.13). For patients with T2D who had selected cardiometabolic risk factors within target ranges, compared with controls, risk of arrythmia and conduction abnormalities for T2D vs not were: AF/AFl (HR 1.09, 95% CI 1.05-1.14), the composite of SND, AV-block or pacemaker implantation (HR 1.06, 95% CI 0.94-1.18), IVCB (HR 0.80, 95% CI 0.60-0.98), and for VT/VF (HR 0.97, 95% CI 0.80-1.17). Cox models showed a linear risk increase for SBP and BMI, while eGFR showed a U-shaped association. Individuals with T2D had a higher risk of arrhythmias and conduction abnormalities than controls, but excess risk associated with T2D was virtually not evident among patients with T2D with all risk factors within target range. BMI, SBP and eGFR displayed significant associations with outcomes among patients with T2D., (© 2023. The Author(s).)

Background: New-onset postoperative atrial fibrillation (POAF) after cardiac surgery is associated with worse short- and long-term outcomes. Although the clinical presentation of POAF varies substantially, almost all studies model it with a dichotomous yes or no variable. We explored potential associations between the clinical course of POAF and long-term outcome., Methods: This retrospective, observational, single-center study included 6435 coronary artery bypass grafting and/or valve patients between 2010 and 2018. POAF patients were grouped into spontaneous/pharmacologic conversion to sinus rhythm, sinus rhythm after electrical cardioversion, and sustained AF at discharge. Multivariable Cox regression models adjusted for age, sex, type of surgery, comorbidities, and early-initiated oral anticoagulation were used to study associations between the clinical course of POAF and long-term risk for mortality, ischemic stroke, thromboembolic events, heart failure hospitalization, and major bleeding. Median follow-up time was 3.8 years (range, 0-8.3)., Results: POAF occurred in 2172 patients (33.8%), 94.9% of whom converted to sinus rhythm before discharge. Of these, 73.6% converted spontaneously or with pharmacologic treatment and 26.4% after electrical cardioversion. Both sustained AF and electrical cardioversion were independently associated with an increased long-term risk for heart failure (adjusted hazard ratio for sustained AF at discharge, 2.55 [95% confidence interval, 1.65-3.93; P < .001]; adjusted hazard ratio for electrical cardioversion, 1.28 [95% confidence interval, 1.00-1.65; P = .049]) but not with increased long-term risk for death, thromboembolic complications, or bleeding., Conclusions: A more complicated POAF course is associated with increased long-term risk for heart failure hospitalization but not for all-cause mortality or thromboembolic complications., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

There are numerous sex-related differences in cardiac electrophysiology and arrhythmia propensity but very little knowledge about the reasons. Difference in body size has been proposed as one reason and was tested in this study of >20 cardiac electrophysiology parameters in 319 (158 women) apparently healthy 50- to 64-yr-old subjects from a randomly enrolled population sample, the pilot SCAPIS (Swedish Cardiopulmonary Bioimaging Study), using Frank vectorcardiography. We studied conventional conduction intervals, parameters reflecting electrical heterogeneity (dispersion) in the ventricles, QRS- and T-vector directions, spatial QRS-T angles, and T-vector loop morphology. Body surface area (BSA; 2 methods) and lean body mass (LBM), both estimated from body weight and height, were used as body size parameters. According to multivariable linear regression analysis adjusted for sex, there was no association between electrophysiological parameters and body size apart from QRS duration and QRSarea. In conclusion, most electrophysiological parameters assessed completely noninvasively and showing statistically significant differences between women and men on the group level show no association with BSA or LBM. Scaling (indexing) the electrophysiological parameters for body size parameters is therefore not an option. Consequently, the explanation for the sex-related electrophysiological differences should be sought along other lines. NEW & NOTEWORTHY We sought explanations for sex-related differences in >20 cardiac electrophysiology parameters including conventional conduction intervals in 319 (158 women) apparently healthy 50- to 64-yr-old subjects using Frank vectorcardiography, a novelty. Our hypothesis that body size was partly explanatory for such differences had to be refuted apart from QRS duration and QRSarea. Scaling (indexing) electrophysiological parameters for body size is therefore not an option and explanations for electrophysiological sex-related differences are to be sought elsewhere.

Hysteresis, a ubiquitous regulatory phenomenon, is a salient feature of the adaptation of ventricular repolarization duration to heart rate (HR) change. We therefore compared the QT interval adaptation to rapid HR increase in patients with the long QT syndrome type 1 (LQT1) versus healthy controls because LQT1 is caused by loss-of-function mutations affecting the repolarizing potassium channel current I Ks , presumably an important player in QT hysteresis. The study was performed in an outpatient hospital setting. HR was increased in LQT1 patients and controls by administering an intravenous bolus of atropine (0.04 mg/kg body weight) for 30 s. RR and QT intervals were recorded by continuous Frank vectorcardiography. Atropine induced transient expected side effects but no adverse arrhythmias. There was no difference in HR response (RR intervals) to atropine between the groups. Although atropine-induced ΔQT was 48% greater in 18 LQT1 patients than in 28 controls (p < 0.001), QT adaptation was on average 25% faster in LQT1 patients (measured as the time constant τ for the mono-exponential function and the time for 90% of ΔQT; p < 0.01); however, there was some overlap between the groups, possibly a beta-blocker effect. The shorter QT adaptation time to atropine-induced HR increase in LQT1 patients on the group level corroborates the importance of I Ks in QT adaptation hysteresis in humans and shows that LQT1 patients have a disturbed ultra-rapid cardiac memory. On the individual level, the QT adaptation time possibly reflects the effect-size of the loss-of-function mutation, but its clinical implications need to be shown., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Purpose: Patients with WPW syndrome have an increased mortality rate compared to the general population. Although asymptomatic preexcitation has previously been considered benign, recent studies have found that also asymptomatic patients have clinical and electrophysiological factors associated with increased risk of sudden cardiac death. This study compares the baseline electrophysiological characteristics of accessory pathways in symptomatic and asymptomatic patients with preexcitation. We hypothesized that a significant proportion of asymptomatic patients has inducible orthodromic tachycardia during programmed electrical stimulation., Methods: This retrospective study includes 1853 patients with preexcitation who underwent invasive electrophysiological testing in two Swedish University Hospitals between 1991 and 2018. The mean age was 36 ± 17 years with a range of 3-89 years. Thirty-nine percent was women. A total of 269 patients (15%) were children younger than 18 years. Electrophysiological data included effective refractory period of the accessory pathway (APERP, in 1069 patients), tachycardia cycle length, inducibility and type of tachycardia, and AP localization., Results: A total of 1703 (93%) patients reported symptoms suggesting tachyarrhythmias before the study and 128 (7%) were asymptomatic. The proportion of potentially dangerous pathways with short APERP (≤ 250 ms) were similar in symptomatic and asymptomatic patients (187/949, 20% vs. 25/108, 23%) (P = 0.40) as was the mean APERP (303 ± 68 ms vs. 307 ± 75) (P = 0.61). The proportion of patients who had inducible arrhythmia was larger in the symptomatic group (64% vs. 31%) (P < 0.001)., Conclusion: The results of this study strengthen the present guideline recommendation (IIA) to consider invasive risk assessment in patients with asymptomatic preexcitation., (© 2022. The Author(s).)

This commentary refers to a case report describing dual ventricular responses following a single P-wave, which is an unusual but possibly underdiagnosed phenomenon. The AV node synchronizes atrial and ventricular mechanical functions, acts as an electrical filter protecting the ventricles from high heart rates during atrial fibrillation and flutter and is also a back-up generator if the sinus node fails. Dual AV-nodal pathways are the substrate for the relatively common AV-nodal re-entrant tachycardia (AVNRT), which is curable by ablation. Ablation is also the therapy of choice when dual ventricular responses cause palpitations with or without AVNRT, or in rare cases of continuously impaired ventricular mechanical function.

Background The CHA 2 DS 2 -VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke or TIA [transient ischemic attack], vascular disease, age 65 to 74 years, sex category female; 2 indicates 2 points, otherwise 1 point) scoring system is recommended to guide decisions on oral anticoagulation therapy for stroke prevention in patients with nonsurgery atrial fibrillation. A score ≥1 in men and ≥2 in women, corresponding to an annual stroke risk exceeding 1%, warrants long-term oral anticoagulation provided the bleeding risk is acceptable. However, in patients with new-onset postoperative atrial fibrillation, the optimal risk stratification method is unknown. The aim of this study was therefore to evaluate the CHA 2 DS 2 -VASc scoring system for estimating the 1-year ischemic stroke risk in patients with new-onset postoperative atrial fibrillation after coronary artery bypass grafting. Methods and Results All patients with new-onset postoperative atrial fibrillation and without oral anticoagulation after first-time isolated coronary artery bypass grafting performed in Sweden during 2007 to 2017 were eligible for this registry-based observational cohort study. The 1-year ischemic stroke rate at each step of the CHA 2 DS 2 -VASc score was estimated using a Kaplan-Meier estimator. Of the 6368 patients included (mean age, 69.9 years; 81% men), >97% were treated with antiplatelet drugs. There were 147 ischemic strokes during the first year of follow-up. The ischemic stroke rate at 1 year was 0.3%, 0.7%, and 1.5% in patients with CHA 2 DS 2 -VASc scores of 1, 2, and 3, respectively, and ≥2.3% in patients with a score ≥4. A sensitivity analysis, with the inclusion of patients on anticoagulants, was performed and supported the primary results. Conclusions Patients with new-onset atrial fibrillation after coronary artery bypass grafting and a CHA 2 DS 2 -VASc score <3 have such a low 1-year risk for ischemic stroke that oral anticoagulation therapy should probably be avoided.

Background: Atrial fibrillation negatively impacts physical fitness and health-related quality of life. We recently showed that 3 months of physiotherapist-led exercise-based cardiac rehabilitation improves physical fitness and muscle function in elderly patients with permanent atrial fibrillation and concomitant diseases. Little is, however, known about the consequences for physical fitness, physical activity level, and health-related quality of life after ending the rehabilitation period., Methods: Prospective 3 months follow-up study of 38 patients out of 40 eligible (10 women) who, as part of a randomized controlled trial, had completed a 3 months physiotherapist-led cardiac rehabilitation resulting in improved physical fitness,. In the current study, the participants were instructed to refrain from exercise for 3 months after completion of the rehabilitation period. Primary outcome measure was physical fitness measured as highest achieved workload using an exercise tolerance test. Secondary outcome measures were muscle function (muscle endurance tests), physical activity level (questionnaire and accelerometer), and health-related quality of life, (Short Form-36), as in the preceding intervention study. We used the Wilcoxon Signed Rank test to analyse differences between the end of rehabilitation and at follow-up. The effect size was determined using Cohen's d ., Results: Exercise capacity and exercise time significantly decresead between end of rehabilitation and at follow-up (p < .0001 for both). A significant reduction in shoulder flexion repetitions (p = .006) was observed as well as reduced health-related quality of life in the Short Form-36 dimensions Physical Function (p = .042), Mental Health (p = .030), and Mental Component Score (p = .035). There were, however, no changes regarding objective and subjective physical activity measurements., Conclusion: In older patients with permanent atrial fibrillation, previously achieved improvements from physiotherapist-led exercise-based cardiac rehabilitation in physical fitness and muscle function were lost, and health-related quality of life was impaired after ending the rehabilitation period. A strategy for conserving improvements after a rehabilitation period is essential., (© 2022. The Author(s).)

Background: Regional differences in ventricular activation sequence and action potential duration and morphology result in dispersion in ventricular repolarization (VR). VR dispersion is a key factor in arrhythmogenesis. We studied the adaptation of global VR dispersion in humans during normal and abnormal ventricular activation, and the relation to the QT adaptation (hysteresis)., Methods: We measured global VR dispersion as T amplitude, T area, and ventricular gradient (VG), using continuous Frank vectorcardiography, in response to abrupt and sustained atrial (AP) or ventricular pacing (VP) aiming at 120 bpm, in 21 subjects with permanent pacemakers., Results: Following pacing start, VR adaptation showed an initially rapid and complex tri-phasic pattern, most pronounced for T amplitude. There were major differences in the patterns of VR dispersion adaptation following abrupt AP vs VP, confirming that the adaptation pattern is activation dependent. In response to AP, an instantaneous decrease in VR dispersion occurred, followed by an increase and then a slow decrease, all at a lower level than baseline. In contrast, following VP there was an immediate increase to ~4× baseline in T amplitude and T area (but not in VG), with a subsequent biphasic adaptation lasting longer during VP than AP. The initial rapid changes occurred within the time for QT adaptation to reach steady-state., Conclusions: Our results corroborate and expand data from animal and invasive human studies, showing similarities of the adaptation pattern on different scales. The initial rapidly changing VR adaptation phase presumably reflects a window of increased vulnerability to arrhythmias., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: To assess whether the prevailing rhythm at the time of replying to symptom and health-related quality of life (HR-QoL) questionnaires impacts the findings., Method: A total of 150 patients from the randomized Catheter Ablation Compared with Pharmacological Therapy for Atrial Fibrillation-trial, comparing atrial fibrillation (AF) ablation versus drugs, were included. The effect of the prevailing rhythm on the outcome results of the HR-QoL 36-Item Short-Form Health Survey, the symptom severity questionnaire (SSQ), and the European Heart Rhythm Association (EHRA) score for classification of AF-related symptoms was assessed., Results: AF as the prevailing rhythm was independently associated with a significantly lower Vitality score; 18.4 points lower (95% confidence interval -32.7 to -4.1, p = .01) compared with sinus rhythm when adjusted for AF burden, median duration of episode, number of episodes, beta-blocker use, type of AF, and sex. The presence of AF did not affect the General Health score compared with sinus rhythm, nor did it influence symptoms assessed by the SSQ or EHRA score., Conclusion: The observation that the presence of AF versus sinus rhythm when conducting HR-QoL tests had a negative impact on its outcome, leaving symptom-related questionnaires unaffected, implies that the prevailing rhythm should be taken into account when results of HR-QoL questionnaires are interpreted., (© 2021 The Authors. Journal of Cardiovascular Electrophysiology Published by Wiley Periodicals LLC.)

Aims: To assess the relation between atrial fibrillation (AF) characteristics and health-related quality of life (QoL), and which AF characteristic had the greatest impact., Method: The AF characteristics burden (percentage of time in AF), duration and number of AF episodes/month were obtained from implantable cardiac monitors during the 2-month run-in period in 150 patients included in the randomized CAPTAF trial comparing early ablation and antiarrhythmic drug therapy. The QoL was measured by the General Health and Vitality dimensions of the 36-Item Short-Form Health Survey. AF characteristics were analysed continuously and in quartiles (Q1-Q4)., Results: Greater AF burden (p = 0.003) and longer AF episodes (p = 0.013) were associated with impaired QoL (Vitality score only) in simple linear regression analyses. Greater AF burden was, however, the only AF characteristic associated with lower QoL, when adjusted for sex, type of AF, hypertension, heart rate above 110 beats per minute during AF, and beta-blocker use in multiple linear regression analyses. For every 10% increase in AF burden there was a 1.34-point decrease of Vitality score (95% confidence interval (CI) -2.67 to -0.02, p = 0.047). The Vitality score was 12 points lower (95% CI -22.73 to -1.27, p = 0.03) in patients with an AF burden > 33% (Q4) versus those with < 0.45% (Q1), but only in unadjusted analysis., Conclusion: AF burden had a greater impact on QoL (Vitality), than the duration and number of AF episodes, corroborating that AF burden may be the preferred outcome measure of rhythm control in trials including relatively healthy AF populations., Competing Interests: Dr Blomström-Lundqvist reports receiving grants from Medtronic during the conduct of the study; and personal fees from Bayer, Sanofi, Boston Scientific, and Merck Sharp & Dohme outside the submitted work. Dr Bergfeldt reports receiving personal fees from Sanofi, Bristol-Myers Squibb, Bayer, and Pfizer outside the submitted work. Dr Raatikainen reports receiving grants from Biosense Webster outside the submitted work. All remaining authors have declared no conflicts of interest., (© 2021 The Authors.)

Background The long-term impact of new-onset postoperative atrial fibrillation (POAF) after coronary artery bypass grafting and the benefit of early-initiated oral anticoagulation (OAC) in patients with POAF are uncertain. Methods and Results All patients who underwent coronary artery bypass grafting without preoperative atrial fibrillation in Sweden from 2007 to 2015 were included in a population-based study using data from 4 national registries: SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies), National Patient Registry, Dispensed Drug Registry, and Cause of Death Registry. POAF was defined as any new-onset atrial fibrillation during the first 30 postoperative days. Cox regression models (adjusted for age, sex, comorbidity, and medication) were used to assess long-term outcome in patients with and without POAF, and potential associations between early-initiated OAC and outcome. In a cohort of 24 523 patients with coronary artery bypass grafting, POAF occurred in 7368 patients (30.0%), and 1770 (24.0%) of them were prescribed OAC within 30 days after surgery. During follow-up (median 4.5 years, range 0‒9 years), POAF was associated with increased risk of ischemic stroke (adjusted hazard ratio [aHR] 1.18 [95% CI, 1.05‒1.32]), any thromboembolism (ischemic stroke, transient ischemic attack, or peripheral arterial embolism) (aHR 1.16, 1.05‒1.28), heart failure hospitalization (aHR 1.35, 1.21‒1.51), and recurrent atrial fibrillation (aHR 4.16, 3.76‒4.60), but not with all-cause mortality (aHR 1.08, 0.98‒1.18). Early initiation of OAC was not associated with reduced risk of ischemic stroke or any thromboembolism but with increased risk for major bleeding (aHR 1.40, 1.08‒1.82). Conclusions POAF after coronary artery bypass grafting is associated with negative prognostic impact. The role of early OAC therapy remains unclear. Studies aiming at reducing the occurrence of POAF and its consequences are warranted.

Background: The heart rate (HR) corrected QT interval (QTc) is crucial for diagnosis and risk stratification in the long QT syndrome (LQTS). Although its use has been questioned in some contexts, Bazett's formula has been applied in most diagnostic and prognostic studies in LQTS patients. However, studies on which formula eliminates the inverse relation between QT and HR are lacking in LQTS patients. We therefore determined which QT correction formula is most appropriate in LQTS patients including the effect of beta blocker therapy and an evaluation of the agreement of the formulae when applying specific QTc limits for diagnostic and prognostic purposes., Methods: Automated measurements from routine 12-lead ECGs from 200 genetically confirmed LQTS patients from two Swedish regions were included (167 LQT1, 33 LQT2). QT correction was performed using the Bazett, Framingham, Fridericia, and Hodges formulae. Linear regression was used to compare the formulae in all patients, and before and after the initiation of beta blocking therapy in a subgroup (n = 44). Concordance analysis was performed for QTc ≥ 480 ms (diagnosis) and ≥500 ms (prognosis)., Results: The median age was 32 years (range 0.1-78), 123 (62%) were female and 52 (26%) were children ≤16 years. Bazett's formula was the only method resulting in a QTc without relation with HR. Initiation of beta blocking therapy did not alter the result. Concordance analyses showed clinically significant differences (Cohen's kappa 0.629-0.469) for diagnosis and prognosis in individual patients., Conclusion: Bazett's formula remains preferable for diagnosis and prognosis in LQT1 and 2 patients., (© 2020 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Adequate adaptation of ventricular repolarization (VR) duration to changes in heart rate (HR) is important for cardiac electromechanical function and electrical stability. We studied the QT and QT peak adaptation in response to abrupt start and stop of atrial and ventricular pacing on two occasions with an interval of at least 1 mo in 25 study subjects with permanent pacemakers. Frank vectorcardiography was used for data collection. Atrial or ventricular pacing was performed for 8 min aiming at a cycle length (CL) of 500 ms. We measured the immediate response (IR), the time constant (τ) of the exponential phase, and T90 End, the time to reach 90% change of QT and QT peak from baseline to steady state during and after pacing. During atrial pacing, the CL decreased on average 45% from mean (SD) 944 (120) to 518 (46) ms and QT decreased on average 18% from 388 (20) to 318 (17) ms. For QT, T90 End was 103 (24) s and 126 (15) s after start versus stop of atrial pacing; a difference of 24 (27) s ( P = 0.006). The response pattern was similar for τ but IR did not differ significantly between pacing start and stop. The response pattern was similar for QT peak and also for QT and QT peak following ventricular pacing start and stop. The coefficients of variation for repeated measures were 7%-21% for T90 End and τ. In conclusion, the adaptation of VR duration was significantly more rapid following increasing than decreasing HR and intraindividually a relatively reproducible process. NEW & NOTEWORTHY We studied the duration of ventricular repolarization (VR) adaptation and its hysteresis, following increasing and decreasing heart rate by abrupt start and stop of 8-min atrial or ventricular pacing in study subjects with permanent pacemakers and repeated the protocol with ≥1 mo interval, a novel approach. VR adaptation was significantly longer following decreasing than increasing heart rate corroborating previous observations. Furthermore, VR adaptation was intraindividually a reproducible and, hence, robust phenomenon, a novel finding.

Background: Wide QRS-T angles and inflammatory activity are markers of future cardiovascular events including sudden cardiac death (SCD). The association between wide QRS-T angles and inflammatory activation is however not fully understood., Methods: 1,094 study participants of both sexes, 50-64 years old, were included from a randomly selected population-based cohort as a part of the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot study. Serum samples were analyzed for markers of inflammation, cardiac wall stress/injury, and the metabolic syndrome. Wide QRS-T angles were defined using Frank vectorcardiography. Variables were analyzed through unsupervised principal component analysis (PCA) as well as Orthogonal Projections to Latent Structures (OPLS) modeling. In addition, a subset of study participants was analyzed in a post hoc matched group design., Results: Wide QRS-T angles correlated positively with markers of inflammation, cardiac wall stress/injury, the metabolic syndrome, and male sex in both PCA and OPLS models. In the matched post hoc analysis, participants with wide QRS-T angles had significantly higher counts of white blood cells (WBC) and neutrophils in comparison with matched controls. WBC as well as the number of neutrophils, monocytes, basophils, eosinophils and levels of C-reactive protein, IL-1, IL-4, IL-6, TNF-α, and NT-pro-BNP were also significantly higher in comparison with healthy controls., Conclusions: Markers of inflammatory activation and cardiac injury/wall stress were significantly higher in the presence of wide QRS-T angles. These results corroborate an association between abnormal electrophysiological function and inflammatory activation and may have implications for the prediction of SCD., (© 2020 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Background: A vectorcardiography approach to electrocardiology contributes to the non-invasive assessment of electrical heterogeneity in the ventricles of the heart and to risk stratification for cardiac events including sudden cardiac death. The aim of this study was to develop an automatic method that identifies a representative QRST complex (QRSonset to Tend) from a Frank vectorcardiogram (VCG). This method should provide reliable measurements of morphological VCG parameters and signal when such measurements required manual scrutiny., Methods: Frank VCG was recorded in a population-based sample of 1094 participants (550 women) 50-65 years old as part of the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot. Standardized supine rest allowing heart rate stabilization and adaptation of ventricular repolarization preceded a recording period lasting ≥5 minutes. In the Frank VCG a recording segment during steady-state conditions and with good signal quality was selected based on QRST variability. In this segment a representative signal-averaged QRST complex from cardiac cycles during 10s was selected. Twenty-eight morphological parameters were calculated including both conventional conduction intervals and VCG-derived parameters. The reliability and reproducibility of these parameters were evaluated when using completely automatic and automatic but manually edited annotation points., Results: In 1080 participants (98.7%) our automatic method reliably selected a representative QRST complex where its instability measure effectively identified signal variability due to both external disturbances ("noise") and physiologic and pathophysiologic variability, such as e.g. sinus arrhythmia and atrial fibrillation. There were significant sex-related differences in 24 of 28 VCG parameters. Some VCG parameters were insensitive to the instability value, while others were moderately sensitive., Conclusion: We developed an automatic process for identification of a signal-averaged QRST complex suitable for morphologic measurements which worked reliably in 99% of participants. This process is applicable for all non-invasive analyses of cardiac electrophysiology including risk stratification for cardiac death based on such measurements., Competing Interests: The authors have declared that no competing interests exist.

Background: The spatial peak and mean QRS-T angles are scientifically but not clinically established risk factors for cardiovascular events including cardiac death. The study aims were to compare these angles, assess their association with hypertension (HT) and diabetes mellitus (DM), and explore the relation between the mean QRS-T angle and the ventricular gradient (VG; reflecting electrical heterogeneity), which both are derived from the QRSarea and Tarea vectors., Methods: Altogether 1094 participants (aged 50-65 years, 550 women) from the pilot of the population-based Swedish CArdioPulmonary bioImage Study with Frank vectorcardiographic recordings were included and divided into 5 subgroups: apparently healthy n = 320; HT n = 311; DM n = 33; DM + HT n = 53; miscellaneous conditions n = 377. Abnormal peak and mean QRS-T angles were defined as >95th percentile., Results: Peak QRS-T angles were generally narrower than the mean QRS-T angles; both were narrower in women than in men. Abnormal peak (>124°) and/or mean (>119°) QRS-T angles were found in 73 participants (6.7%). The concordance regarding abnormal versus normal-borderline QRS-T angles was good (Cohen's kappa 0.61). The prevalence of abnormal angles varied from 2.5% in healthy to 21.2% in DM. There was an inverse logarithmical relation between the mean QRS-T angle and the VG., Conclusions: The peak and mean QRS-T angles are not interchangeable but complementary. DM, HT, sex and absence of disease are important determinants of both QRS-T angles. The mean QRS-T angle and the VG relationship is complex. All three VCG derived measures reflect related but differing electrophysiological properties and have potential prognostic value vis-à-vis cardiovascular events., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The duration of ventricular repolarization (VR) and its spatial and temporal heterogeneity are central elements in arrhythmogenesis. We studied the adaptation of VR duration and dispersion and their relationship in healthy human subjects during atrial pacing., Methods: Patients 20-50 years of age who were scheduled for ablation of supraventricular tachycardia without preexcitation but otherwise healthy were eligible. Vectorcardiography recordings with Frank leads were used for data collection. Incremental atrial pacing from a coronary sinus electrode was performed by decrements of 10ms/cycle from just above sinus rate, and then kept at a fixed heart rate (HR) just below the Wenckebach rate for ≥5min and then stopped. VR duration was measured as QT and VR dispersion as T area, T amplitude and ventricular gradient. The primary measure (T90 End) was the time to reach 90% change from baseline to the steady state value during and after pacing., Results: A complete study protocol was accomplished in 9 individuals (6 women). VR duration displayed a monophasic adaptation during HR acceleration lasting on average 20s. The median (Q1-Q3) T90 End for QT was 85s (51-104), a delay by a factor >4. All dispersion measures displayed a tri-phasic response pattern during HR acceleration and T90 End was 3-5 times shorter than for VR duration., Conclusions: Even during close to "physiological" conditions, complex and differing response patterns in VR duration and dispersion measures followed changes in HR. Extended knowledge about these responses in disease conditions might assist in risk evaluation and finding therapeutic alternatives., (© 2019 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals, LLC.)

Objective: To study the occurrence of torsades de pointes (TdP) ventricular tachycardia in relation to use of drugs labelled with TdP risk, using two nationwide Swedish registers., Design: Prospective register-based cohort study., Setting: Entire Sweden., Participants: Persons aged ≥18 years prescribed and dispensed any drug classified with TdP risk during 2006-2017, according to CredibleMeds. Persons with a registered TdP diagnosis during the study period, using drugs labelled with known (TdP 1), possible (TdP 2) or conditional (TdP 3) risk at the incident of TdP were examined., Primary Outcome Measures: Occurrence of TdP in relation to exposure rates for individual drugs with TdP risk., Secondary Outcome Measures: Concurrent use of more than one TdP-labelled drug in a person with a TdP diagnosis., Results: During the study period, 410 TdP cases using drugs with TdP risk labels at the incident were registered; 205 women and 205 men, mean age 74.0 and 71.5 years, respectively. Antidepressants dominated (129/410, 30%), followed by antiarrhythmics (17%). Diuretics and gastric acid-secretion inhibitors, with TdP risk related to induction of hypokalaemia or hypomagnesaemia, were used in 56% and 32% of the 410 TdP cases, respectively. Among the most used antidepressants, citalopram with known TdP 1 risk was associated with both a higher absolute number and incidence of TdP per 100 000 users (two to four times), compared with mirtazapine with possible (TdP 2), and sertraline with conditional (TdP 3) risk. Multiple risk factors, including advanced age, cardiovascular disease and treatment with more than one TdP-classified drug, were frequently observed., Conclusions: Antidepressants followed by antiarrhythmics dominated among TdP risk drugs used by adults with TdP diagnosis, the majority being ≥65 years. TdP risk class and concomitant medication should be considered when prescribing antidepressants to older patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Efficacy and safety of dronedarone was shown in the ATHENA trial for paroxysmal or persistent atrial fibrillation (AF) patients. Further trials revealed safety concerns in patients with heart failure and permanent AF. This review summarizes insights from recent real-world studies and meta-analyses, including reports on efficacy, with focus on liver safety, mortality risk in patients with paroxysmal/persistent AF, and interactions of dronedarone with direct oral anticoagulants. Reports of rapidly progressing liver failure in dronedarone-prescribed patients in 2011 led to regulatory cautions about potential liver toxicity. Recent real-world evidence suggests dronedarone liver safety profile is similar to other antiarrhythmics and liver toxicity could be equally common with many Class III antiarrhythmics. Dronedarone safety concerns (increased mortality in patients with permanent AF) were raised based on randomized controlled trials (RCT) (ANDROMEDA and PALLAS), but comedication with digoxin may have increased the mortality rates in PALLAS, considering the dronedarone-digoxin pharmacokinetic (PK) interaction. Real-world data on apixaban-dronedarone interactions and edoxaban RCT observations suggest no significant safety risks for these drug combinations. Median trough plasma concentrations of dabigatran 110 mg during concomitant use with dronedarone are at acceptable levels, while PK data on the rivaroxaban-dronedarone interaction are unavailable. In RCTs and real-world studies, dronedarone significantly reduces AF burden and cardiovascular hospitalizations, and demonstrates a low risk for proarrhythmia in patients with paroxysmal or persistent AF. The concerns on liver safety must be balanced against the significant reduction in hospitalizations in patients with non-permanent AF and low risk for proarrhythmias following dronedarone treatment., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: To describe electrocardiographic (ECG) development in patients with ankylosing spondylitis (AS) and identify associations between baseline characteristics and cardiac conduction disturbances (CCD) at 5-year follow-up., Methods: In a longitudinal cohort study, 172 patients (54% men, mean age (SD) of 50 (13) years at baseline) with AS underwent ECG, physical examination, questionnaires and laboratory testing at baseline and at 5-year follow-up. Descriptive statistics and univariate and age- and sex-adjusted logistic regression analyses were used. CCD included both atrioventricular and intraventricular blocks., Results: Twenty-three of the 172 patients (13.4%) had a CCD at follow-up. Eight patients had developed a new CCD and eight had normalised their ECG. In the age- and sex-adjusted analyses, CCD at baseline (OR 24.8, 95% CI 7.3 to 84.5), male sex (OR 6.4, 95% CI 2.0 to 20.8), history of anterior uveitis (OR 4.4, 95% CI 1.3 to 14.5), higher ASDAS-CRP (OR 2.3, 95% CI 1.3 to 4.0), greater waist circumference (OR 1.3, 95% CI 1.1 to 1.6, per 5 cm), and medication with antiplatelets (OR 7.0, 95% CI 1.5 to 31.8) and beta-blockers (OR 3.4, 95% CI 1.0 to 11.5) were associated with a CCD at follow-up. Higher age and longer symptom duration were highly correlated and were both associated with a CCD at follow-up., Conclusions: The presence of CCD in AS is in part dynamic and associated with both AS and non-AS characteristics. Our results suggest that patients especially prone to present with CCDs are older men with a previous CCD, longer symptom duration, higher AS disease activity, a history of anterior uveitis and medication reflecting cardiovascular disease., Competing Interests: Competing interests: LJ has received advisory board fees from Eli Lilly, Pfizer and Novartis. HFdE has received advisory board fees from Sandoz, AbbVie and Novartis, and unrestricted grant from Novartis., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Galectin-1 is a recently discovered adipokine that increases with obesity and increased energy intake in adipose tissue. Our aim was to assess whether serum galectin-1 is associated with type 2 diabetes (T2D) and other parameters of the metabolic syndrome independently of body mass index (BMI) in a cohort from the general population., Methods: In this cross-sectional population-based cohort study from the western part of Sweden, we investigated associations between serum galectin-1, clinical characteristics and inflammatory markers in 989 women and men aged 50-65 years [part of the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort]., Results: We showed in linear models that serum galectin-1 was independently and: (1) inversely associated with T2D (p < 0.05) and glucose (p < 0.05); and (2) positively associated with age (p < 0.01), sex (p < 0.01), BMI (p < 0.01), insulin (p < 0.01) and C-reactive protein (p < 0.01). Furthermore, galectin-1 demonstrated univariate correlations with triglycerides (r = 0.20, p < 0.01), homeostasis model assessment for insulin resistance (r = 0.24, p < 0.01), tumor necrosis factor-α (r = 0.24, p < 0.01), interleukin-6 (IL-6; r = 0.20, p < 0.01) and HbA1c (r = 0.14, p < 0.01)., Conclusion: In a cross-sectional study of a middle-aged population, we showed that serum galectin-1 is: (1) inversely associated with T2D independently of BMI; and (2) independently associated with other markers of the metabolic syndrome These results warrant prospective and functional studies on the role of galectin-1 in T2D., (© 2019 The Authors.)

Objective: To study the performance and cardiovascular function after a 3-week training camp in athletes competing in an anaerobically dominant sport., Methods: Twenty-three competitive 400-m athletes were enrolled in this non-randomized study, 17 took part in a 3-week training camp in South-Africa (intervention), but one declined follow-up assessment, while 6 pursued in-door winter training in Sweden and served as controls. Electrocardiography, transthoracic echocardiography, blood test analyses, maximal exercise tolerance test, and a 300-m sprint test with lactate measurements ([La]peak) were performed before and after the training camp period., Results: At baseline, there were no clinically significant pathological findings in any measurements. The training period resulted in improved 300m-sprint performance [n = 16; running time 36.71 (1.39) vs. 35.98 (1.13) s; p<0.01] and higher peak lactate values. Despite 48% more training sessions than performed on home ground (n = 6), myocardial biomarkers decreased significantly (NT-pro BNP -38%; p<0.05, troponin T -16%; p<0.05). Furthermore, resting heart rate (-7%; p<0.01) and left ventricular systolic and diastolic volumes decreased -6% (p<0.01) and -10% (p<0.05), respectively., Conclusions: Intense physical activity at training camp improved the performance level, likely due to improved anaerobic capacity indicated by higher [La]peak. There were no clinically significant adverse cardiac changes after this period of predominantly anaerobic training., Competing Interests: CMM is the co-founder of Stockholm Exercise Analytics and Silicon Valley Exercise Analytics. This does not alter our adherence to PLOS ONE policies on sharing data and materials. These sponsors had no role in the study design, in the collection, analysis and interpretation of data, in the writing of the report; or in the decision to submit the article for publication.

Importance: Quality of life is not a standard primary outcome in ablation trials, even though symptoms drive the indication., Objective: To assess quality of life with catheter ablation vs antiarrhythmic medication at 12 months in patients with atrial fibrillation., Design, Setting, and Participants: Randomized clinical trial at 4 university hospitals in Sweden and 1 in Finland of 155 patients aged 30-70 years with more than 6 months of atrial fibrillation and treatment failure with 1 antiarrhythmic drug or β-blocker, with 4-year follow-up. Study dates were July 2008-September 2017. Major exclusions were ejection fraction <35%, left atrial diameter >60 mm, ventricular pacing dependency, and previous ablation., Interventions: Pulmonary vein isolation ablation (n = 79) or previously untested antiarrhythmic drugs (n = 76)., Main Outcomes and Measures: Primary outcome was the General Health subscale score (Medical Outcomes Study 36-Item Short-Form Health Survey) at baseline and 12 months, assessed unblinded (range, 0 [worst] to 100 [best]). There were 26 secondary outcomes, including atrial fibrillation burden (% of time) from baseline to 12 months, measured by implantable cardiac monitors. The first 3 months were excluded from rhythm analysis., Results: Among 155 randomized patients (mean age, 56.1 years; 22.6% women), 97% completed the trial. Of 79 patients randomized to receive ablation, 75 underwent ablation, including 2 who crossed over to medication and 14 who underwent repeated ablation procedures. Of 76 patients randomized to receive antiarrhythmic medication, 74 received it, including 8 who crossed over to ablation and 43 for whom the first drug used failed. General Health score increased from 61.8 to 73.9 points in the ablation group vs 62.7 to 65.4 points in the medication group (between-group difference, 8.9 points; 95% CI, 3.1-14.7; P = .003). Of 26 secondary end points, 5 were analyzed; 2 were null and 2 were statistically significant, including decrease in atrial fibrillation burden (from 24.9% to 5.5% in the ablation group vs 23.3% to 11.5% in the medication group; difference -6.8% [95% CI, -12.9% to -0.7%]; P = .03). Of the Health Survey subscales, 5 of 7 improved significantly. Most common adverse events were urosepsis (5.1%) in the ablation group and atrial tachycardia (3.9%) in the medication group., Conclusions and Relevance: Among patients with symptomatic atrial fibrillation despite use of antiarrhythmic medication, the improvement in quality of life at 12 months was greater for those treated with catheter ablation compared with antiarrhythmic medication. Although the study was limited by absence of blinding, catheter ablation may offer an advantage for quality of life., Trial Registration: clinicaltrialsregister.eu Identifier: 2008-001384-11.

Background: Proper adaptation of ventricular repolarization (VR) to rapid heart rate (HR) increase is crucial for cardiac electro-mechanical function. The pattern and temporal aspects of this adaptation and its components (duration and dispersion) during normal conduction are, however, incompletely known in humans and were the topic of this study., Methods & Results: The VR duration (QT & QTpeak) and dispersion (Tamplitude, Tarea & ventricular gradient; VG) responses were studied by continuous vectorcardiogram after a bolus injection of atropine 0.04mg/kg b.w. in 31 healthy young adults (16 men). The primary measure (T90 End) was the time to reach 90% change from baseline to end value 300s later. Mean (SD) of T90 End was 23 (9) s for a 41% RR decrease, 130 (35) s for a 16% QTend decrease and 110 (36) s for a 19% QTpeak decrease; the response was single-exponential for these measures. For 35-43% decreases of Tamplitude, Tarea & VG, mean (SD) of T90 End were 21 (10), 38 (20) and 40 (23) s and the response pattern was double-exponential with varying overshoot., Conclusions: VR duration and dispersion responses to a very rapid HR increase during normal conduction differed substantially. In contrast to the well-known single-exponential delay in VR duration adaptation the responses of VR dispersion measures were double-exponential and much more rapid. We describe a new and completely non-invasive phenotypic characterization of different components of VR adaptation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Prediction of sudden cardiac death (SCD) after acute coronary syndromes (ACS) remains a challenge. Although electrophysiology measures obtained by 3-D vectorcardiography (VCG) shortly after ACS may be useful predictors of SCD, they have not been adopted into clinical practice. The main objective of our study was to assess whether the VCG-derived QRS-T area angle (between area vectors) and the QRS-T angle (between maximum vectors) have additional value beyond standard risk factors in predicting SCD after ACS., Methods and Results: We studied 643 consecutive ACS patients for whom data on VCG and echocardiography during the index hospitalization were available. Seventy-seven patients (12%) died, 37 (6%) from SCD and 21 (3%) from other cardiac causes during the 30-month follow-up. After adjusting for 9 standard risk factors (age, sex, diabetes, previous stroke, left ventricular ejection fraction; and estimated glomerular filtration rate, heart rate, systolic blood pressure<100mmHg, and Killip class>1 on admission), QRS-T area angle and QRS-T angle were shown to have independent predictive value for both SCD and all cardiac deaths. Reclassification analysis showed that both measures had additional predictive value beyond the 9 standard risk factors. For SCD, net reclassification improvements for QRS-T area angle and QRS-T angle were 46% and 45% and relative integrated discriminative improvements were 16% and 13% (vs the average~11% of the 9 standard risk factors)., Conclusions: The VCG-derived QRS-T area angle and QRS-T angle improved prediction of SCD after ACS beyond standard risk factors. Further evaluation of their clinical utility and cost-effectiveness is therefore warranted., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The aim of this study was to assess the prevalence of aortic regurgitation and any relation to disease activity and specific human leukocyte antigen (HLA)-B27 subtypes in patients with ankylosing spondylitis., Methods: Transthoracic echocardiography was performed in 187 patients (105 men), mean age (SD) 50 (13) years, and mean disease duration 24 (13) years, and was related to demographic, clinical, radiographic, electrocardiographic, and laboratory data., Results: Aortic regurgitation was found in 34 patients (18%; 95% confidence interval [CI], 12%-24%): mild in 24, moderate in 9, and severe in one. The prevalence was significantly higher than expected from population data. Conduction system abnormalities were documented in 25 patients (13%; 95% CI, 8%-18%), and significantly more likely in the presence of aortic regurgitation (P = .005), which was related to increasing age and longstanding disease, and increased from ~20% in the 50s to 55% in the 70s. It was also independently associated with disease duration, with higher modified Stoke Ankylosing Spondylitis Spine Score, and with a history of anterior uveitis. HLA-B27 was present in similar proportions in the presence vs absence of aortic regurgitation. For comparison, clinically significant coronary artery disease was present in 9 patients (5%; 95% CI, 2%-8%)., Conclusion: Patients with ankylosing spondylitis frequently have cardiac abnormalities, but they more often consist of disease-related aortic regurgitation or conduction system abnormalities than manifestations of atherosclerotic heart disease. Because aortic regurgitation or conduction abnormalities might cause insidious symptoms not easily interpreted as of cardiac origin, we suggest that both electrocardiography and echocardiography evaluation should be part of the routine management of patients with ankylosing spondylitis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

"Cardiac memory" is an altered repolarization phenotype resulting from prior cardiac rate, rhythm, and/or activation changes. The various types of memory depend on biophysical properties of cardiac ion channels, trafficking of those channels, and/or epigenetic changes in the genes determining the channels. The processes that engage the memory function presage changes in function that ultimately can lead to pathological remodeling. Hence--rather than completely benign--memory may be a warning of disease to come. This article considers the forms, the mechanisms, and the clinical expression of cardiac memory., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Early repolarization defined as antero-lateral ST-segment elevation exists in 1-2 % of the general population and has been considered a benign ECG finding for decades. However, early repolarization, defined as infero-lateral J-waves, has in recent studies been associated with an increased - albeit low - risk of sudden and cardiovascular death. This ECG pattern is present in 3-13% of the general population. However, exercise training can induce all types of early repolarization, and the prevalence in the athletic population rises to 20-90%. There is large variability between sports (higher in endurance athletes) and also throughout the season (higher during times of peak fitness). In athletes, early repolarization, regardless of type, is considered benign. In asymptomatic non-athletes, the absolute risk is too low to use this ECG finding in clinical practice. In individuals with J-wave syndrome, on the other hand, ICD implantation should be strongly considered to prevent sudden cardiac death.

Introduction: Atrial fibrillation (AF) is the most common form of arrhythmia in humans and is associated with substantial morbidity and mortality. Obesity and diabetes have been linked to myocardial lipotoxicity - a condition where the heart accumulates and produces toxic lipid species. We hypothesized that obesity and diabetes were involved in the pathophysiology of AF by means of promoting a lipotoxic phenotype in atrial muscle, and that AF predicts mortality in cardiac care patients., Methods: Our study consists of two parts. The first part is a registry study based on prospective data obtained through the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA) from hospitals in western Sweden. All consecutive patients between 2006 and 2011 admitted to coronary care unit (CCU) with sinus rhythm (SR) or AF were included in the analysis. Multivariate logistic regression and Cox proportional-hazards regression were used to test whether diabetes and obesity were independent predictors of AF at admission to CCU and whether AF was associated with increased one-year mortality. In the second part we obtained atrial biopsies from 54 patients undergoing cardiac surgery and performed lipidomic analysis for a detailed qualitative and quantitative analysis of lipid species including triglycerides (TAG), ceramides (CER), phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), sphyngomyelins (SM), free cholesterol (FC), cholesterol esters (CEs) and diacylglycerols (DAGs)., Results: Between 2006 and 2011, 35232 patients were admitted to CCUs in western Sweden, mostly due to ischemic heart disease, heart failure, arrhythmia, syncope and chest pain. The mean age was 66years and 58.7% were male. There was a high prevalence of obesity (20.3%) and diabetes (16.8%). Obesity (OR 1.35, 95% CI 1.17-1.56, P<0.001) and severe obesity (1.6, 95% CI 1.29-1.99, P<0.001) were independent predictors of AF but diabetes was not (OR=0.92, 95% CI=0.82-1.04). AF increased one-year mortality (HR 1.32, 95% CI 1.16-1.50, P<0.001). Lipidomic analysis revealed that atrial TAG content was substantially lower in the AF patients (P<0.05). No quantitative difference was found in the content of CER, PC, LPC, PE, SM, FC, CE and DAG, between the patients who had AF or sinus rhythm at admission to the CCU. AF patients had greater proportion of polyunsaturated DAG (P<0.05) while no difference was found in saturated DAG., Conclusion: Obesity but not diabetes is an independent predictor of AF and AF is associated with increased one-year mortality in this CCU population. AF is associated with quantitative and qualitative alterations in atrial lipid content but not with lipotoxicity., (Copyright © 2015. Published by Elsevier Inc.)

Background: The use of vectorcardiography (VCG) has regained interest, however, original Frank-VCG equipment is rare. This study compares the measured VCGs with those synthesized from the 12-lead electrocardiogram (ECG) in patients with heart failure and conduction abnormalities, who are candidate for cardiac resynchronization therapy (CRT)., Methods: In 92 CRT candidates, Frank-VCG and 12-lead ECG were recorded before CRT implantation. The ECG was converted to a VCG using the Kors method (Kors-VCG) and the two methods were compared using correlation and Bland-Altman analyses., Results: Variables calculated from the Frank- and Kors-VCG showed correlation coefficients between 0.77 and 0.90. There was a significant but small underestimation by the Kors-VCG method, relative bias ranging from -1.9% ± 4.6% (QRS-T angle) to -9.4% ± 20.8% (T area)., Conclusion: The present study shows that it is justified to use Kors-VCG calculations for VCG analysis, which enables retrospective VCG analysis of previously recorded ECGs in studies related to CRT., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Impaired dominant hand function in stroke patients is a common clinical problem. Functional improvement after focal spasticity therapy is well documented but knowledge about central correlates is sparse. Brain activity was therefore followed during therapy with repeated functional magnetic resonance imaging (fMRI). The purpose was to analyse motor function and central nervous system (CNS) correlates in response to a standardized motor task in stroke patients after a comprehensive focal spasticity therapy., Methods: Six consecutive first-time chronic stroke patients [4 women; mean age (SD) 66 (10) years] with right-sided hand paresis and spasticity were studied. Peripheral effects after focal spasticity management including intramuscular botulinum toxin type A (BoNT-A) injections were assessed on 3 occasions (baseline, 6 and 12 weeks) with functional tests. Brain effects were assessed on the same occasions by fMRI blood oxygen level dependent (BOLD) technique during a standardized motor task focusing on the motor and pre-motor cortex (Brodmann areas, BA4a, BA4p & BA6). For reference 10 healthy individuals [5 women; mean age (SD) of 51(8) years], were studied twice with ≥ 6 weeks interval., Results: After therapy there was a significant reduction in spasticity and functional improvement in 5 of 6 patients. In response to the motor task there was a ~1.5 - 3% increase in brain activity in the motor and pre-motor cortex. At baseline, this increase was larger in the non-injured (ipsilateral) than in the contralateral hemisphere. Compared with healthy subjects the patients showed a significantly (2-4.5 times) higher brain activity, especially on the ipsilateral side. After therapy, there was a larger decrease in the ipsilateral and a minor decrease in the contralateral response, i.e. a clear lateralization of left-to-right in a normalizing direction in all areas., Conclusions: Comprehensive focal spasticity management was also in this study associated with brain reorganization in a "normalizing" left/right lateralization direction in addition to improved motor function. Furthermore, quantification of BOLD intensity in specified BAs showed reduced neuronal "over-activity" in the injured brain after therapy.

Current optimization of atrioventricular (AV) and interventricular (VV) intervals in cardiac resynchronization therapy (CRT) is time consuming and subject to noise. We aimed to prove the principle that the best hemodynamic effect of CRT is achieved by cancelation of opposing electrical forces, detectable from the QRS morphology in the 3D vectorcardiogram (VCG). Different degrees of left (LV) and right ventricular (RV) pre-excitation were induced, using variation in AV intervals during LV pacing in 20 patients with left bundle branch block (LBBB) and variation in VV intervals during biventricular pacing in 18 patients with complete AV block or atrial fibrillation. The smallest QRS vector area identified stimulation intervals with minimal systolic stretch (median difference [IQR] 20 ms [-20, 20 ms] and maximal hemodynamic response (10 ms [-20, 40 ms]). Reliability of VCG measurements was superior to hemodynamic measurements. This study proves the principle that VCG analysis may allow easy and reliable optimization of stimulation intervals in CRT patients.

Background: QRS duration and left bundle branch block (LBBB) morphology are used to select patients for cardiac resynchronization therapy (CRT). We investigated whether the area of the QRS complex (QRSAREA) on the 3-dimensional vectorcardiogram (VCG) can improve patient selection., Methods: VCG (Frank orthogonal lead system) was recorded prior to CRT device implantation in 81 consecutive patients. VCG parameters, including QRSAREA, were assessed, and compared to QRS duration and morphology. Three LBBB definitions were used, differing in requirement of mid-QRS notching. Responders to CRT (CRT-R) were defined as patients with ≥15% reduction in left ventricular end systolic volume after 6months of CRT., Results: Fifty-seven patients (70%) were CRT-R. QRSAREA was larger in CRT-R than in CRT non-responders (140±42 vs 100±40 μVs, p<0.001) and predicted CRT response better than QRS duration (AUC 0.78 vs 0.62, p=0.030). With a 98μVs cutoff value, QRSAREA identified CRT-R with an odds ratio (OR) of 10.2 and a 95% confidence interval (CI) of 3.4 to 31.1. This OR was higher than that for QRS duration >156ms (OR=2.5; 95% CI 0.9 to 6.6), conventional LBBB classification (OR=5.5; 95% CI 0.9 to 32.4) or LBBB classification according to American guidelines (OR=4.5; 95% CI 1.6 to 12.6) or Strauss (OR=10.0; 95% CI 3.2 to 31.1)., Conclusion: QRSAREA is an objective electrophysiological predictor of CRT response that performs at least as good as the most refined definition of LBBB., Condensed Abstract: In 81 candidates for cardiac resynchronization therapy (CRT) we measured the area of the QRS complex (QRSAREA) using 3-dimensional vectorcardiography. QRSAREA was larger in echocardiographic responders than in non-responders and predicted CRT response better than QRS duration and than simple LBBB criteria. QRSAREA is a promising electrophysiological predictor of CRT response., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: The objective of this study is to investigate the time course of autonomic tone changes after a first-time endurance running race participation and associations with postexertional high-sensitivity troponin (hsTnT) levels in middle-aged males., Methods: Male (n = 42) first-time long-distance running race (Lidingöloppet 30 km) participants ≥45 yr (50.5 ± 5) were examined. HR and HR variability (HRV) in the time domain (SDANN) was measured continuously from 2 d before to 4 d after the race using a wireless cardiovascular monitor that also recorded arrhythmia episodes. In addition, subjects were assessed pre- and postrace by medical history and physical examination, 12-lead ECG, blood tests including hsTnT, and echocardiography., Results: Compared with corresponding prerace values, nighttime (2:00-4:00 a.m.) HR was significantly elevated (63.6 ± 9.4 vs 53.9 ± 8.3 bpm, P < 0.001) on the first night postrace, whereas HRV remained reduced for a median of 64 h (interquartile range, 51-102 h). A prolonged HR recovery period (r = 0.48, P = 0.005) and a larger reduction in postrace HRV (r = -0.49, P = 0.003) correlated with higher postrace hsTnT levels. The association between reduced HRV and higher hsTnT remained significant after multivariate analysis (β = -0.48, P = 0.01). No sustained ventricular arrhythmias were recorded, but atrial fibrillation occurred in two subjects., Conclusion: Endurance running race participation caused a prolonged alteration of autonomic tone. More marked and prolonged changes were associated with higher levels of hsTnT, suggesting that the magnitude of troponin increase after strenuous exercise may reflect the magnitude of exercise-induced cardiovascular stress.

Purpose: This study aimed to assess the prevalence and patterns of early repolarization (ER) in middle-age long-distance runners, its relation to cardiac structure and function, and its response to strenuous physical activity., Methods: Male first-time cross-country race participants >45 yr were assessed pre- and postrace by medical history and physical examination, 12-lead ECG, vectorcardiography, blood tests, and echocardiography. ER was defined either as ST elevation or J wave and categorized according to localization and morphology., Results: One hundred and fifty-one subjects (50 ± 5 yr) were evaluated before the race, and 47 subjects were evaluated after the race. Altogether, 67 subjects (44%) had ER. Subjects with versus without ER had a lower resting HR (56 ± 8 vs 69 ± 9 bpm, P = 0.02), lower body mass index (24 ± 2 vs 25 ± 3 kg·m(-2), P < 0.001), higher training volume (3.0 ± 2.6 vs 2.1 ± 2.7 h·wk(-1), P = 0.03), and faster 30-km running times (194 ± 28 vs 208 ± 31 min, P = 0.01). Vectorcardiography parameters in subjects with ER showed more repolarization heterogeneity: vector gradient (QRS-T(area)) (120 ± 25 vs 92 ± 29 μVs, P < 0.001), T(area) (105 ± 18 vs 73 ± 23 μVs, P < 0.001), and T(amplitude) (0.63 ± 0.13 vs 0.53 ± 0.16 mm, P < 0.001); these parameters were inversely related to HR (r = -0.37 to -0.48, P < 0.001). ER disappeared in 15 (75%) of 20 subjects after the race., Conclusions: ER is a common finding in middle-age male runners. This ECG pattern, regardless of morphology and localization, is associated with normal cardiac examinations including noninvasive electrophysiology, features of better physical conditioning, and disappears after strenuous exercise in most cases. These findings support that ER should be regarded as a common and training-related finding also in middle-age physically active men.

Objective: To study effects of ischemia-reperfusion on ventricular electrophysiology in humans by three-dimensional electrocardiography., Methods: Fifty-seven patients with first-time acute anterior ST elevation myocardial infarction were monitored from admission and >24h after symptom onset with continuous vectorcardiography (VCG; modified Frank orthogonal leads). Global ventricular depolarization and repolarization (VR) measures were compared at maximum vs. minimum ST vector magnitude (STVM) (median 208; 111-303 vs. 362; 165-1359min after symptom onset)., Results: At maximum vs. minimum STVM the Tarea (overall VR dispersion) almost tripled (118 vs. 41μVs; p<0.0001), the T-loop bulginess was 90% greater (Tavplan 0.91 vs 0.48μV; p<0.0001), and Tpeak-end/QT was 39% larger (0.32 vs 0.23; p<0.0001). QRSarea (overall dispersion of depolarization) was 12% larger at maximum STVM, while QRS duration was 10% longer at minimum STVM., Conclusions: Ischemia-reperfusion was accompanied by profound and transient alterations of VR dispersion, while changes in depolarization were modest and delayed., (Copyright © 2014 Elsevier Inc. All rights reserved.)