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Purpose: We wanted to illustrate the right-to-left impulse propagation routes during sinus in patients with paroxysmal atrial fibrillation (PAF), as alterations in conduction patterns have been linked to the pathogenesis of PAF, and as no large patient materials have been published.Methods: Patients underwent 3-D electroanatomical contact mapping prior to catheter ablation. The site of the earliest left atrial (LA) activation was determined.Results: Three different interatrial routes were identified, either as solitary pathways (36/50 patients, 72%) or in their combinations (14/50). Bachmann's bundle (BB) was involved in the majority of the cases with solitary routes (25/36). More seldom, impulse propagation occurred near the oval fossa (FO) (7/36) or the coronary sinus ostium (4/36). In patients with combined routes, both the BB (10/14) and FO routes (11/14) were included in most cases.Conclusions: In PAF patients, LA can be activated during sinus rhythm through three distinct connections, either encompassing a single route or via any combination of these connections. In one third, the earliest LA activation occurs outside BB. The knowledge of the propagation patterns may give insight into the pathophysiology of PAF and into refining ablation therapy. [ABSTRACT FROM AUTHOR]

Background: Patients with hypertrophic cardiomyopathy (HCM) have a high incidence of atrial fibrillation. They also have a longer P-wave duration than healthy controls, indicating conduction alterations. Previous studies have demonstrated orthogonal P-wave morphology alterations in patients with paroxysmal atrial fibrillation. In the present study, the P-wave morphology of patients with HCM was compared with that of matched controls in order to explore the nature of the atrial conduction alterations.Methods and Results: A total of 65 patients (45 men, mean age 49 +/- 15) with HCM were included. The control population (n = 65) was age and gender matched (45 men, mean age 49 +/- 15). Five minutes of 12-lead ECG was recorded. The data were subsequently transformed to orthogonal lead data, and unfiltered signal-averaged P-wave analysis was performed. The P-wave duration was longer in the HCM patients compared to the controls (149 +/- 22 vs 130 +/- 16 ms, P < 0.0001). Examination of the P-wave morphology demonstrated changes in conduction patterns compatible with interatrial conduction block of varying severity in both groups, but a higher degree of interatrial block seen in the HCM population. These changes were most prominent in the Leads Y and Z.Conclusion: The present study suggests that the longer P-wave duration observed in HCM patients may be explained by a higher prevalence of block in one or more of the interatrial conduction routes. [ABSTRACT FROM AUTHOR]

Objectives: To examine cardiovascular autonomic function in middle-aged people with long-term cervical and upper thoracic spinal cord injury (SCI) compared with the general population, and explore if the neurological level of injury (NLI) is related to cardiovascular autonomic function., Design: Population-based cross-sectional study with matched controls., Setting: Outpatient SCI unit in Southern Sweden., Participants: Twenty-five individuals (20% women, mean age 58 years and mean time since injury 28 years, NLI C2-T6, American Spinal Injury Association Impairment Scale A-C) from the Swedish SPinal Cord Injury Study on Cardiopulmonary and Autonomic Impairment (SPICA). Matched controls were obtained from the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) at a ratio of 5:1., Interventions: Not applicable., Outcome Measures: 24 h electrocardiography and deep breathing tests. 24 h ambulatory blood pressure (BP) monitoring and orthostatic BP tests., Results: In individuals with SCI compared with controls, heart rate variability (24h mean SD of the normal-to-normal interval 112 ms vs 145 ms, P < 0.001) and diastolic orthostatic BP increase (2.0 and 9.4 mmHg, P < 0.001), were significantly lower, whereas BP variability was significantly higher (24h mean systolic SD BP 17.8 mmHg vs 15.7 mmHg, P = 0.029). Circadian patterns of heart rate variability and BP (lack of nocturnal dip) were significantly different among the individuals with SCI than controls. Higher NLI was significantly (P < 0.05) correlated with impairments to various cardiovascular autonomic function variables., Conclusions: This exploratory study indicates that cardiovascular autonomic function is impaired in middle-aged people with long-term cervical and upper thoracic SCI compared with the general non-SCI population, and more pronounced with a higher NLI. Future research is needed to understand the pathophysiological mechanisms underlying these impairments, and the prognostic significance for individuals with SCI., Trial Registration: ClinicalTrials.gov identifier: NCT03515122.

Background: Electrocardiographic abnormalities are common in arrhythmogenic right ventricular cardiomyopathy and are included in the 2010 Task Force Criteria. Their time course, however, remains uncertain. In this retrospective observational study, we aimed to assess the long-term evolution of electrocardiographic characteristics and their relation to ventricular arrhythmias., Methods and Results: Three hundred fifty-three patients with arrhythmogenic right ventricular cardiomyopathy as per the 2010 Task Force Criteria with 6871 automatically processed 12-lead digital ECGs were included. The relationship between the electrocardiographic parameters and the risk of ventricular arrhythmias was assessed at 10 years from the first ECG. Electrocardiographic parameters were compared between the first contact ECG, the ECG at diagnosis, and the most recent ECG. Median time between the first and the latest ECG was 6 [interquartile range, 1-14] years. Reductions of QRS voltage, R- and T-wave amplitudes between the first, diagnostic, and the latest ECGs were observed across precordial and extremity leads. Mean QRS duration increased from 96 to 102 ms ( P <0.001), terminal activation duration (V 1 ) from 47 to 52 ms ( P <0.001), and QTc from 419 to 432 ms ( P <0.001). T-wave inversions in leads V 3 to V 6 and aVF at first ECG were associated with ventricular arrhythmias (adjusted hazard ratio [HR adj ][V 3 ], 2.03 [95% CI, 1.23-3.34] and HR adj [aVF], 1.87 [95% CI, 1.13-3.08])., Conclusions: Depolarization and repolarization parameters evolved over time in patients with arrhythmogenic right ventricular cardiomyopathy, supporting the progressive nature of arrhythmogenic right ventricular cardiomyopathy. Electrocardiographic abnormalities may be detected before diagnosis and might, although not fulfilling the 2010 Task Force Criteria, be markers of early disease. T-wave inversion in leads V 3 or aVF before diagnosis was associated with ventricular arrhythmias during follow-up.

Introduction: Information about autonomic nervous system (ANS) activity may offer insights about atrial fibrillation (AF) progression and support personalized AF treatment but is not easily accessible from the ECG. In this study, we propose a new approach for ECG-based assessment of respiratory modulation in atrioventricular (AV) nodal refractory period and conduction delay. Methods: A 1-dimensional convolutional neural network (1D-CNN) was trained to estimate respiratory modulation of AV nodal conduction properties from 1-minute segments of RR series, respiration signals, and atrial fibrillatory rates (AFR) using synthetic data that replicates clinical ECG-derived data. The synthetic data were generated using a network model of the AV node and 4 million unique model parameter sets. The 1D-CNN was then used to analyze respiratory modulation in clinical deep breathing test data of 28 patients in AF, where an ECG-derived respiration signal was extracted using a novel approach based on periodic component analysis. Results: We demonstrated using synthetic data that the 1D-CNN can estimate the respiratory modulation from RR series alone with a Pearson sample correlation of r = 0.805 and that the addition of either respiration signal ( r = 0.830), AFR ( r = 0.837), or both ( r = 0.855) improves the estimation. Discussion: Initial results from analysis of ECG data suggest that our proposed estimate of respiration-induced autonomic modulation, a resp , is reproducible and sufficiently sensitive to monitor changes and detect individual differences. However, further studies are needed to verify the reproducibility, sensitivity, and clinical significance of a resp ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Plappert, Engström, Platonov, Wallman and Sandberg.)

Background: To avoid causing a thromboembolic event in patients undergoing catheter ablation for atrial fibrillation (AF), patients are treated with oral anticoagulants (OAC) prior to the procedure. Despite being on anticoagulants, some patients develop a left atrial appendage thrombus (LAAT). To exclude the presence of LAAT, transesophageal ultrasound (TEE) is performed in all patients prior to the procedure. We hypothesized continuous treatment with anticoagulants would result in a low prevalence of LAAT, in patients with low CHA 2 DS 2 -VASc score., Method: Medical records of consecutive patients planned to undergo AF ablation at Lund University Hospital during the years 2018-2020 were reviewed retrospectively. Examination protocols from transesophageal and transthoracic echocardiography were examined for LAAT and spontaneous echo contrast (SEC). Patients with LAAT and SEC were compared to patients without using Mann-Whitney U-test and Pearson Chi-squared analysis to test for correlation., Results: Of 553 patients, three patients (0.54%) had LAAT, and 18 (3.25%) had spontaneous contrast (SEC). Patients with LAAT or SEC had a higher CHA 2 DS 2 -VASc score, more often presented in AF at TEE and less often had a normal sized left atrium., Conclusion: There is a low prevalence of LAAT and SEC in patients with AF scheduled for pulmonary vein isolation. Patients with SEC or LAAT tend to have paroxysmal AF less often and more often presented in AF at admission. No patients with CHA 2 DS 2 -VASc 0, paroxysmal AF, normal sized left atrium and sinus rhythm at TEE were found to have LAAT or SEC., (© 2024 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Background: The ABC-stroke score is a risk scheme for prediction of stroke or systemic embolism (SE) in atrial fibrillation (AF). This study sought to examine whether the score could be useful in predicting stroke in AF-naïve individuals and risk stratifying for AF screening., Methods and Results: The LOOP (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals) study randomized 6004 AF-naïve individuals aged 70 to 90 years with stroke risk factors to either screening with an implantable loop recorder and anticoagulation upon detection of new-onset AF episodes ≥6 minutes, or usual care. A total of 5781 participants had available ABC-stroke score at baseline and were included in this secondary analysis: 4170 (72.1%) with an estimated stroke/SE risk ≤1%/year versus 1611 (27.9%) with an estimated stroke/SE risk >1%/year. Having an annual ABC-stroke risk >1% was associated with stroke/SE, stroke/SE/cardiovascular death, and all-cause death (hazard ratio, 1.82 [95% CI, 1.44-2.21], 2.17 [95% CI, 1.80-2.62], and 2.19 [95% CI, 1.87-2.56], respectively). For screening with implantable loop recorder versus usual care, no significant reduction in these study outcomes was obtained in any ABC-stroke risk groups ( P >0.0500 for all), with no signal toward interaction ( P interaction >0.2500 for all). Similar findings were yielded when assessing the ABC-stroke score as a continuous variable., Conclusions: In an elderly, AF-naïve population with additional stroke risk factors, a higher ABC-stroke score could identify individuals with increased stroke risk. However, this risk score may not be useful in pinpointing those more likely to benefit from AF screening and subsequent preventive treatment. These findings should be considered as hypothesis generating and warrant further study., Registration: URL: https://www.clinicaltrials.gov; unique identifier: NCT02036450.

Background and Aims: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC., Methods: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed., Results: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans., Conclusions: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Atrial fibrillation (AF) is the most common arrhythmia, associated with significant burdens to patients and the healthcare system. The atrioventricular (AV) node plays a vital role in regulating heart rate during AF by filtering electrical impulses from the atria. However, it is often insufficient in regards to maintaining a healthy heart rate, thus the AV node properties are modified using rate-control drugs. Moreover, treatment selection during permanent AF is currently done empirically. Quantifying individual differences in diurnal and short-term variability of AV-nodal function could aid in personalized treatment selection. Methods: This study presents a novel methodology for estimating the refractory period (RP) and conduction delay (CD) trends, and their uncertainty in the two pathways of the AV node during 24 h using non-invasive data. This was achieved by utilizing a network model together with a problem-specific genetic algorithm and an approximate Bayesian computation algorithm. Diurnal variability in the estimated RP and CD was quantified by the difference between the daytime and nighttime estimates, and short-term variability was quantified by the Kolmogorov-Smirnov distance between adjacent 10-min segments in the 24-h trends. Additionally, the predictive value of the derived parameter trends regarding drug outcome was investigated using several machine learning tools. Results: Holter electrocardiograms from 51 patients with permanent AF during baseline were analyzed, and the predictive power of variations in RP and CD on the resulting heart rate reduction after treatment with four rate control drugs was investigated. Diurnal variability yielded no correlation to treatment outcome, and no prediction of drug outcome was possible using the machine learning tools. However, a correlation between the short-term variability for the RP and CD in the fast pathway and resulting heart rate reduction during treatment with metoprolol ( ρ = 0.48, p < 0.005 in RP, ρ = 0.35, p < 0.05 in CD) were found. Discussion: The proposed methodology enables non-invasive estimation of the AV node properties during 24 h, which-indicated by the correlation between the short-term variability and heart rate reduction-may have the potential to assist in treatment selection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Karlsson, Platonov, Ulimoen, Sandberg and Wallman.)

Background: 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., Methods: 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., Results: 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)., Conclusion: 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Patients with heart failure (HF) and bradycardia may be eligible for different types of cardiac implantable electronic devices (CIED), depending on the presence of atrioventricular conduction disease, age, and comorbidities. We aimed to assess the prognosis for these patients, after CIED implantation, stratified for the type of CIED device., Methods: All patients with preexisting HF diagnosis who received a CIED with a right ventricular lead during the period 2005-2018 in Sweden were identified via the pacemaker registry. Data were crossmatched with the population registry and national disease registries. The outcome was 5-year risk of HF hospitalization and mortality., Results: A total of 37,745 patients were included in the study. Comparing demographics for implantable cardioverter defibrillator versus pacemaker implants, median age was 66 years versus 83 years, 20% versus 41% were female, 64% versus 50% had ischemic heart disease, and 35% versus 67% had atrial fibrillation (all p &lt; 0.001). Five-year mortality was highest in single-chamber pacemaker recipients (61% compared to average 40%, p &lt; 0.001), but the proportion of cardiovascular mortality was highest for cardiac resynchronization therapy (CRT) recipients (68% vs. 63% p &lt; 0.001). Adjusted mortality was higher for pacemaker patients in all age decile groups (ranging from &lt;60 to &gt;90 years old, all p &lt; 0.001), HF hospitalization occurred in 28% (dual-chamber pacemaker) to 39% (CRT-P) of patients, and cause of death was HF in 15% (dual-chamber pacemaker) to 25% (CRT-D), all p &lt; 0.001., Conclusion: In this large real-world cohort of CIED-treated patients with prior HF, demography and mortality data indicate that clinicians chose devices according to the overall status of the patient. HF-related events occurred in all groups but were more common in CRT-treated patients., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

The ECG diagnosis of LVH is predominantly based on the QRS voltage criteria. The classical paradigm postulates that the increased left ventricular mass generates a stronger electrical field, increasing the leftward and posterior QRS forces, reflected in the augmented QRS amplitude. However, the low sensitivity of voltage criteria has been repeatedly documented. We discuss possible reasons for this shortcoming and proposal of a new paradigm. The theoretical background for voltage measured at the body surface is defined by the solid angle theorem, which relates the measured voltage to spatial and non-spatial determinants. The spatial determinants are represented by the extent of the activation front and the distance of the recording electrodes. The non-spatial determinants comprise electrical characteristics of the myocardium, which are comparatively neglected in the interpretation of the QRS patterns. Various clinical conditions are associated with LVH. These conditions produce considerable diversity of electrical properties alterations thereby modifying the resultant QRS patterns. The spectrum of QRS patterns observed in LVH patients is quite broad, including also left axis deviation, left anterior fascicular block, incomplete and complete left bundle branch blocks, Q waves, and fragmented QRS. Importantly, the QRS complex can be within normal limits. The new paradigm stresses the electrophysiological background in interpreting QRS changes, i.e., the effect of the non-spatial determinants. This postulates that the role of ECG is not to estimate LV size in LVH, but to understand and decode the underlying electrical processes, which are crucial in relation to cardiovascular risk assessment., (© 2023 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Background: We aimed to evaluate if optimization by maximizing QRS duration (QRSd) reduction is feasible in an all-comer cardiac resynchronization therapy (CRT) population, and if reduced, QRSd is associated with a better clinical outcome., Methods: Patients with LBBB receiving CRT implants during the period 2015-2020 were retrospectively evaluated. Implants from 2015-2017 were designated as controls. Starting from 2018, an active 12-lead electrogram-based optimization of QRSd reduction was implemented (intervention group). QRSd reduction was evaluated in a structured way at various device AV and VV settings, aiming to maximize the reduction. The primary endpoint was a composite of heart failure hospitalization or death from any cause., Results: A total of 254 patients were followed for up to 6 years (median 2.9 [1.8-4.1]), during which 82 patients (32%) reached the primary endpoint; 53 deaths (21%) and 58 (23%) heart failure hospitalizations. Median QRS duration pre-implant was 162 ms [150-174] and post-implant 146ms [132-160]. Mean reduction in QRS duration was progressively larger for each year during the intervention period, ranging from - 9.5ms in the control group to - 24 in the year 2020 (p = 0.005). QRS reduction > 14 ms (median value) was associated with a lower risk of death or heart failure hospitalization (adjusted HR 0.54 [0.29-0.98] (p = 0.04)., Conclusions: Implementing a general strategy of CRT device optimization by aiming for shorter QRS duration is feasible in a structured clinical setting and results in larger reductions in QRS duration post-implant. In patients with a larger QRS reduction, compared to those with a smaller QRS reduction, there is an association with a better clinical outcome., (© 2023. The Author(s).)

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: The present study aimed at testing the hypothesis that atrial fibrillatory rate (AFR) is predictive of sinus rhythm maintenance after electrical cardioversion., Methods and Results: 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)., Conclusion: 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., Clinical Trial Registration: NCT02112318 (http://www., Clinicaltrials: gov)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Atrial myopathy refers to structural and functional cardiac abnormalities associated with atrial fibrillation and stroke, but appropriate diagnostic criteria are lacking., Objectives: This study aimed to assess prevalence, clinical correlates, and overlap between potential atrial myopathy markers., Methods: The population-based SCAPIS (Swedish CArdioPulmonary bioImage Study) prospectively included 6,013 subjects without atrial fibrillation with 24-hour electrocardiograms. Resting electrocardiograms measuring P-wave indices were collected at 1 screening site (n = 1,201), and a random sample (n = 385) had echocardiographic left atrial volume index (LAVi). Atrial myopathy markers were defined as ≥500 premature atrial complexes/24 h, LAVi ≥34 mL/m 2 , P-wave duration >120 milliseconds, or P-wave terminal force in V 1 >4,000 ms·s. Clinical correlates included age, sex, body mass index, height, smoking, physical activity, coronary artery disease, diabetes, systolic blood pressure, antihypertensive medication, and low education., Results: Atrial myopathy was common; 42% of the sample with all diagnostic modalities available had ≥1 atrial myopathy marker, but only 9% had 2 and 0.3% had ≥3. Only P-wave duration and LAVi were correlated (ρ = 0.10; P = 0.04). Clinical correlates of premature atrial complexes, P-wave indices, and LAVi differed; current smoking (34% increase; P < 0.001), systolic blood pressure (4%/mm Hg increase; P = 0.01), diabetes (35% increase; P = 0.001), and coronary artery disease (71% increase; P = 0.003) were associated with premature atrial complexes, physical activity ≥2 h/wk was associated with increased LAVi (β-coefficient = 3.1; P < 0.0001) and body mass index was associated with P-wave duration (β-coefficient = 0.4/kg/m 2 ; P < 0.0001)., Conclusions: In the general population, indirect markers of atrial myopathy are common but only weakly correlated, and their risk factor patterns are different. More studies are needed to accurately identify individuals with atrial myopathy with diagnostic methods., Competing Interests: Funding Support and Author Disclosures Dr Johnson has received support from the Swedish Society of Medicine; and consulting fees from MEDICALgorithmics, outside the scope of the current study. Drs Johnson and Engström have received support from the Swedish Heart and Lung Foundation and the Swedish Research Council. Dr Platonov has received support from the Swedish Heart-Lung Foundation, grants from the Swedish state under the agreement between the Swedish government and the county councils (the ALF agreement), and donation funds from Skåne University Hospital. Dr Conen has received speaker fees from Servier and BMS/Pfizer, as well as advisory board fees from Roche Diagnostics and Trimedics, all outside of the current study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: The deep breathing test (DBT) is a sensitive test of cardiovagal function. The aim of this study was to explore associations between physical activity and sedentary time, measured by accelerometer, and autonomic function, using DBT., Methods: In the Swedish Cardio-Pulmonary bioImage Study, men and women aged 50-64 were randomly invited from the general population. A total of 4325 subjects who underwent DBT and assessment of physical activity and sedentary time by accelerometery were included. ECG files from 1-min DBT were used to calculate measures of respiratory sinus arrhythmia [RSA; expiration-inspiration (E-I) difference and E/I ratio], heart rate variability [HRV; root mean square of successive differences (RMSSD), standard deviation of heart rates and mean circular resultant]. Low RSA and HRV was defined as the lowest 10% in the population., Results: For accelerometer-assessed physical activity, there were significant associations between high percentage of sedentary time and low E/I (p < 0.01), and low RMSSD (p < 0.01) in an age- and sex-adjusted model, and between percentage of sedentary time and low RMSSD (p = 0.04) in a risk factor-adjusted model. Low RMSSD was less common in those with a high percentage of moderate to vigorous physical activity (p = 0.04, after risk-factor adjustment). These associations became non-significant when further adjusting for heart rate., Conclusion: We report associations between degree of physical activity and indices of autonomic dysfunction in a large population. The relationships were no longer significant after adjustments for heart rate, indicating that the relationship between physical activity and cardiovagal function partly is accounted for by reduced heart rate., (© 2023. The Author(s).)

Background: Multiple cardiac sarcoidosis (CS) diagnostic schemes have been published., Objectives: This study aims to evaluate the association of different CS diagnostic schemes with adverse outcomes. The diagnostic schemes evaluated were 1993, 2006, and 2017 Japanese criteria and the 2014 Heart Rhythm Society criteria., Methods: Data were collected from the Cardiac Sarcoidosis Consortium, an international registry of CS patients. Outcome events were any of the following: all-cause mortality, left ventricular assist device placement, heart transplantation, and appropriate implantable cardioverter-defibrillator therapy. Logistic regression analysis evaluated the association of outcomes with each CS diagnostic scheme., Results: A total of 587 subjects met the following criteria: 1993 Japanese (n = 310, 52.8%), 2006 Japanese (n = 312, 53.2%), 2014 Heart Rhythm Society (n = 480, 81.8%), and 2017 Japanese (n = 112, 19.1%). Patients who met the 1993 criteria were more likely to experience an event than patients who did not (n = 109 of 310, 35.2% vs n = 59 of 277, 21.3%; OR: 2.00; 95% CI: 1.38-2.90; P < 0.001). Similarly, patients who met the 2006 criteria were more likely to have an event than patients who did not (n = 116 of 312, 37.2% vs n = 52 of 275, 18.9%; OR: 2.54; 95% CI: 1.74-3.71; P < 0.001). There was no statistically significant association between the occurrence of an event and whether a patient met the 2014 or the 2017 criteria (OR: 1.39; 95% CI: 0.85-2.27; P = 0.18 or OR: 1.51; 95% CI: 0.97-2.33; P = 0.067, respectively)., Conclusions: CS patients who met the 1993 and the 2006 criteria had higher odds of adverse clinical outcomes. Future research is needed to prospectively evaluate existing diagnostic schemes and develop new risk models for this complex disease., Competing Interests: Funding Support and Author Disclosures Dr Kron was supported by CTSA award No. UL1TR002649 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. Dr Platonov’s cardiac sarcoid research program is funded by The Swedish Heart-Lung Foundation and the Skåne University Hospital. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Prior studies have suggested that the benefit from primary preventive defibrillator treatment for patients with nonischemic cardiomyopathyy, treated with cardiac resynchronization therapy, may be age-dependent. We aimed to compare age-stratified mortality rates and mode of death in patients with nonischemic cardiomyopathy who are treated with either primary preventive cardiac resynchronization therapy with defibrillator (CRT-D) or CRT with pacemaker (CRT-P)., Methods and Results: All patients with nonischemic cardiomyopathy and CRT-P or primary preventive CRT-D who were implanted in Sweden during the period 2005-2020 were included. Propensity scoring was used to create a matched cohort. Primary outcome was all-cause mortality within 5 years. In all, 4027 patients were included: 2334 with CRT-P and 1693 with CRT-D. Crude 5-year mortality was 635 (27%) vs. 246 (15%), P < 0.001. In Cox regression analysis, adjusted for clinically relevant covariables, CRT-D was independently associated with higher 5-year survival [0.72 (0.61-0.85), P < 0.001]. Cardiovascular mortality was similar between groups (62 vs. 64%, P = 0.64), but death from heart failure was more common in the CRT-D group (46 vs. 36%, P = 0.007). In the matched cohort (n = 2414), 5-year mortality was 21% (24 vs. 16%, P < 0.001). In age-stratified analyses, CRT-P was associated with higher mortality in age groups <60 years and 70-79 years, but there was no difference in age groups 60-69 years or 80-89 years., Conclusion: In this nationwide registry-based study, patients with CRT-D had better 5-year survival compared to patients with CRT-P. The interaction between age and mortality reduction was not consistent, but patients with CRT-D aged <60 years had the largest absolute mortality reduction., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Prolonged endurance exercise increase the risk of atrial fibrillation (AF) in men. Functional parameters may help separate physiological from pathological atrial remodeling in athletes. LA mechanical dispersion (LA MD) is associated with AF in the general population, but the associations between prolonged exercise, LA MD and AF are not known., Purpose: To describe LA MD in veteran athletes with and without paroxysmal AF (pAF) and to investigate LA MD's ability to identify veteran athletes with pAF., Methods: Two hundred and ninety-three men, skiers with (n = 57) and without (n = 87) pAF, and controls with (n = 61) and without pAF (n = 88) underwent an echocardiographic exam in sinus rhythm. LA reservoir strain (LASr) was measured, and LA MD defined as the standard deviation of time-to-peak strain (SD-TPS)., Results: Skiers (mean age 70.7 ± 6.7 years) reported an average of 40-50 years of endurance exercise. LA volumes were associated with pAF and athletic status (p < .001). SD-TPS was associated with pAF (p < .001) but not athletic status (p = .173). We found no significant trend between years of exercise and SD-TPS in individuals without AF (p = .893). SD-TPS did not add incremental value in identifying athletes with pAF in addition to clinical markers, QRS width, LA volume, and LASr (p = .056)., Conclusion: LA MD was associated with pAF regardless of athletic status but not related to years of endurance exercise, suggesting LA MD could be a promising marker of pathological atrial remodeling in athletes. However, we found no incremental value of LA MD identifying athletes with pAF when LASr was included in the model., (© 2023 The Authors. Echocardiography published by Wiley Periodicals LLC.)

Aims: Internal and external triggers affect seasonal and circadian variations of myocardial infarction (MI). We aimed to assess sex differences in the common triggers of MI., Methods and Results: A nationwide, retrospective, cross-sectional postal survey study was conducted. Individuals who experienced a MI during holidays and weekdays were identified through the SWEDEHEART registry. Twenty-seven potential MI triggers were rated in regards to occurring more or less than usual during the last 24 h before the MI. Three areas were covered: activities, emotions, and food or alcohol consumption. A logistic regression model was used to identify sex differences for each trigger and odds ratios (ORs) were reported. Four hundred and fifty-one patients, of whom 317 were men, responded. The most commonly reported triggers were stress (35.3%), worry (26.2%), depression (21.1%), and insomnia (20.0%). Women reported emotional triggers including sadness [OR 3.52, 95% confidence interval (CI) 1.92-6.45], stress (OR 2.38, 95% CI 1.52-3.71), insomnia (OR 2.31, 95% CI 1.39-3.81), and upset (OR 2.69, 95% CI 1.47-4.95) to a greater extent than men. Outdoor activity was less reported by women (OR 0.35, 95% CI 0.14-0.87). No significant sex differences were found in other activities or food and alcohol consumption., Conclusion: Self-experienced stress and distress were higher among women prior to MI compared with men. Understanding sex perspectives in acute triggers may help us find preventive strategies and reduce the excess numbers of MI., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Repolarization prolongation can be the earliest electrophysiological change in ischemia, but its role in arrhythmogenesis is unclear. The aim of the present study was to evaluate the early ischemic action potential duration (APD) prolongation concerning its causes, expression in ECG and association with early ischemic ventricular fibrillation (phase 1A VF). Methods: Coronary occlusion was induced in 18 anesthetized pigs, and standard 12 lead ECG along with epicardial electrograms were recorded. Local activation time (AT), end of repolarization time (RT), and activation-repolarization interval (ARIc) were determined as dV/dt minimum during QRS-complex, dV/dt maximum during T-wave, and rate-corrected RT-AT differences, respectively. Patch-clamp studies were done in enzymatically isolated porcine cardiomyocytes. IK(ATP) activation and Ito1 inhibition were tested as possible causes of the APD change. Results: During the initial period of ischemia, a total of 11 pigs demonstrated maximal ARIc prolongation >10 ms at 1 and/or 2.5 min of occlusion (8 and 6 cases at 1 and 2.5 min, respectively) followed by typical ischemic ARIc shortening. The maximal ARIc across all leads was associated with VF development (OR 1.024 95% CI 1.003-1.046, p = 0.025) and maximal rate-corrected QT interval (QTc) (B 0.562 95% CI 0.346-0.775, p < 0.001) in logistic and linear regression analyses, respectively. Phase 1A VF incidence was associated with maximal QTc at the 2.5 min of occlusion in ROC curve analysis (AUC 0.867, p = 0.028) with optimal cut-off 456 ms (sensitivity 1.00, specificity 0.778). The pigs having maximal QTc at 2.5 min more and less than 450 ms significantly differed in phase 1A VF incidence in Kaplan-Meier analysis (log-rank p = 0.007). In the patch-clamp experiments, 4-aminopyridine did not produce any effects on the APD; however, pinacidil activated IK(ATP) and caused a biphasic change in the APD with initial prolongation and subsequent shortening. Conclusion: The transiently prolonged repolarization during the initial period of acute ischemia was expressed in the prolongation of the maximal QTc interval in the body surface ECG and was associated with phase 1A VF. IK(ATP) activation in the isolated cardiomyocytes reproduced the biphasic repolarization dynamics observed in vivo , which suggests the probable role of IK(ATP) in early ischemic arrhythmogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bernikova, Tsvetkova, Gonotkov, Ovechkin, Demidova, Azarov and Platonov.)

Background: Prognostic assessment of ventricular tachycardia (VT) or ventricular fibrillation (VF) in ST-segment elevation myocardial infarction (STEMI) is based mainly on distinguishing between early (<48 hours) and late arrhythmias, and does not take into account its time distribution with regard to reperfusion, or type of arrhythmia., Objective: We analyzed the prognostic value of early ventricular arrhythmias (VAs) in STEMI with regard to their type and timing., Methods: The prespecified analysis of the multicenter prospective Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarctionin Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease evaluated according to Recommended Therapies Registry Trial included 2886 STEMI patients undergoing primary percutaneous coronary intervention (PCI). VA episodes were characterized regarding their type and timing. Survival status at 180 days was assessed through the population registry., Results: Nonmonomorphic VT or VF was observed in 97 (3.4%) and monomorphic VT in 16 (0.5%) patients. Only 3 (2.7%) early VA episodes occurred after 24 hours from symptom onset. VA was associated with higher risk of death (hazard ratio 3.59; 95% confidence interval [CI] 2.01-6.42) after adjustment for age, sex, and STEMI localization. VA after PCI was associated with an increased mortality compared with VA before PCI (hazard ratio 6.68; 95% CI 2.90-15.41). Early VA was associated with in-hospital mortality (odds ratio 7.39; 95% CI 3.68-14.83) but not with long-term prognosis in patients discharged alive. The type of VA was not associated with mortality., Conclusion: VA after PCI was associated with an increased mortality compared with VA before PCI. Long-term prognosis did not differ between patients with monomorphic VT and nonmonomorphic VT or VF, but events were few. VA incidence during 24 to 48 hours of STEMI is negligibly low, thus precluding assessment of its prognostic importance., (© 2022 Heart Rhythm Society. Published by Elsevier Inc.)

Background: A novel risk calculator based on clinical characteristics and noninvasive tests that predicts the onset of clinical sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been proposed and validated by recent studies. It remains unknown whether programmed ventricular stimulation (PVS) provides additional prognostic value., Methods: All patients with a definite ARVC diagnosis, no history of sustained VAs at diagnosis, and PVS performed at baseline were extracted from 6 international ARVC registries. The calculator-predicted risk for sustained VA (sustained or implantable cardioverter defibrillator treated ventricular tachycardia [VT] or fibrillation, [aborted] sudden cardiac arrest) was assessed in all patients. Independent and combined performance of the risk calculator and PVS on sustained VA were assessed during a 5-year follow-up period., Results: Two hundred eighty-eight patients (41.0±14.5 years, 55.9% male, right ventricular ejection fraction 42.5±11.1%) were enrolled. At PVS, 137 (47.6%) patients had inducible ventricular tachycardia. During a median of 5.31 [2.89-10.17] years of follow-up, 83 (60.6%) patients with a positive PVS and 37 (24.5%) with a negative PVS experienced sustained VA ( P <0.001). Inducible ventricular tachycardia predicted clinical sustained VA during the 5-year follow-up and remained an independent predictor after accounting for the calculator-predicted risk (HR, 2.52 [1.58-4.02]; P <0.001). Compared with ARVC risk calculator predictions in isolation (C-statistic 0.72), addition of PVS inducibility showed improved prediction of VA events (C-statistic 0.75; log-likelihood ratio for nested models, P <0.001). PVS inducibility had a 76% [67-84] sensitivity and 68% [61-74] specificity, corresponding to log-likelihood ratios of 2.3 and 0.36 for inducible (likelihood ratio+) and noninducible (likelihood ratio-) patients, respectively. In patients with a ARVC risk calculator-predicted risk of clinical VA events <25% during 5 years (ie, low/intermediate subgroup), PVS had a 92.6% negative predictive value., Conclusions: PVS significantly improved risk stratification above and beyond the calculator-predicted risk of VA in a primary prevention cohort of patients with ARVC, mainly for patients considered to be at low and intermediate risk by the clinical risk calculator.

Background: The recurrence rate of atrial fibrillation (AF) in horses after cardioversion to sinus rhythm (SR) is relatively high. Atrial fibrillatory rate (AFR) derived from surface ECG is considered a biomarker for electrical remodelling and could potentially be used for the prediction of successful AF cardioversion and AF recurrence., Objectives: Evaluate if AFR was associated with successful treatment and could predict AF recurrence in horses., Study Design: Retrospective multicentre study., Methods: Electrocardiograms (ECG) from horses with persistent AF admitted for cardioversion with either medical treatment (quinidine) or transvenous electrical cardioversion (TVEC) were included. Bipolar surface ECG recordings were analysed by spatiotemporal cancellation of QRST complexes and calculation of AFR from the remaining atrial signal. Kaplan-Meier survival curve and Cox regression analyses were performed to assess the relationship between AFR and the risk of AF recurrence., Results: Of the 195 horses included, 74 received quinidine treatment and 121 were treated with TVEC. Ten horses did not cardiovert to SR after quinidine treatment and AFR was higher in these, compared with the horses that successfully cardioverted to SR (median [interquartile range]), (383 [367-422] vs 351 [332-389] fibrillations per minute (fpm), P < .01). Within the first 180 days following AF cardioversion, 12% of the quinidine and 34% of TVEC horses had AF recurrence. For the horses successfully cardioverted with TVEC, AFR above 380 fpm was significantly associated with AF recurrence (hazard ratio = 2.4, 95% confidence interval 1.2-4.8, P = .01)., Main Limitations: The treatment groups were different and not randomly allocated, therefore the two treatments cannot be compared. Medical records and the follow-up strategy varied between the centres., Conclusions: High AFR is associated with failure of quinidine cardioversion and AF recurrence after successful TVEC. As a noninvasive marker that can be retrieved from surface ECG, AFR can be clinically useful in predicting the probability of responding to quinidine treatment as well as maintaining SR after electrical cardioversion., (© 2021 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Background: Several studies suggest that circulating biomarkers of myocardial fibrosis are associated with worse prognosis in subjects with atrial fibrillation (AF). Here, we aimed to explore associations between fibrosis biomarkers, prevalent AF, and left atrial volume (LAV) enlargement in subjects with heart failure (HF). Additionally, we evaluated the prognostic impact of fibrotic biomarkers in HF with co-existing AF., Materials and Methods: Patients hospitalized for HF ( n = 316, mean age 75 years; 30% women) were screened for AF. Seven proteins previously associated with myocardial fibrosis [metalloproteinase inhibitor 4 (TIMP-4), suppression of tumorigenicity 2 (ST-2), galectin-3 (GAL-3), growth/differentiation factor-15 (GDF-15), and matrix metalloproteinase 2, 3, and 9 (MMP-3, MMP-3, and MMP-9, respectively)] were analyzed using a proximity extension assay. Proteins with significant Bonferroni-corrected associations with mortality and re-hospitalization risk were taken forward to multivariable Cox regression analyses. Further, Bonferroni-corrected multivariable logistic regression models were used to study associations between protein plasma levels, prevalent AF, and severely enlarged left atrial volume index (LAVI ≥ 48 ml/m 2 )., Results: Prevalent AF was observed in 194 patients at the hospitalization of whom 178 (92%) were re-hospitalized and 111 (57%) died during the follow-up period. In multivariable logistic regression models, increased plasma levels of TIMP-4, GDF-15, and ST-2 were associated with the prevalence of AF, whereas none of the seven proteins showed any significant association with severely enlarged LAVI. Increased plasma levels of five proteins yielded significant associations with all-cause mortality in patients with co-existing AF; TIMP-4 (HR 1.33; CI95% 1.07-1.66; p = 0.010), GDF-15 (HR 1.30; CI95% 1.05-1.62; p = 0.017), GAL-3 (HR 1.29; CI95% 1.03-1.61; p = 0.029), ST-2 (HR 1.48; CI95% 1.18-1.85; p < 0.001), and MMP-3 (HR 1.33; CI95% 1.09-1.63; p = 0.006). None of the proteins showed any significant association with re-hospitalization risk., Conclusion: In this study, we were able to demonstrate that elevated levels of three plasma proteins previously linked to myocardial fibrosis are associated with prevalent AF in a HF population. Additionally, higher levels of five plasma proteins yielded an increased risk of mortality in the HF population with or without co-existing AF., Competing Interests: Author EB was employed by AstraZeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nezami, Holm, Ohlsson, Molvin, Korduner, Bachus, Zaghi, Dieden, Platonov, Jujic and Magnusson.)

In myocardial ischemia, melatonin confers antiarrhythmic action, but its electrocardiographic expression is unclear. We aimed to evaluate the effects of melatonin treatment on electrocardiogram (ECG) parameters reflecting major arrhythmogenic factors and to test the association of these parameters with ventricular fibrillation (VF) incidence. Myocardial ischemia was induced by 40 min coronary artery occlusion in 25 anesthetized pigs. After induction of ischemia, 12 and 13 animals were given melatonin or placebo, respectively. Twelve-lead ECGs were recorded and durations of QRS, QT, Tpeak-Tend intervals and extrasystolic burden were measured at baseline and during occlusion. During ischemia, VF episodes clustered into early and delayed phases (<10 and >20 min, respectively), and QRS duration was associated with VF incidence. QT interval and extrasystolic burden did not differ between the groups. The Tpeak-Tend interval was progressively prolonged, and the prolongation was less pronounced in the treated animals. QRS duration increased, demonstrating two maxima (5−10 and 25 min, respectively). In the melatonin group, the earlier maximum was blunted, and VF development in this period was prevented. Thus, acute melatonin treatment prevented excessive prolongation of the QRS and Tpeak-Tend intervals in the porcine myocardial infarction model, and QRS duration can be used for the assessment of antiarrhythmic action of melatonin.

The heart rate during atrial fibrillation (AF) is highly dependent on the conduction properties of the atrioventricular (AV) node. These properties can be affected using β -blockers or calcium channel blockers, mainly chosen empirically. Characterization of individual AV-nodal conduction could assist in personalized treatment selection during AF. Individual AV nodal refractory periods and conduction delays were characterized based on 24-hour ambulatory ECGs from 60 patients with permanent AF. This was done by estimating model parameters from a previously created mathematical network model of the AV node using a problem-specific genetic algorithm. Based on the estimated model parameters, the circadian variation and its drug-dependent difference between treatment with two β -blockers and two calcium channel blockers were quantified on a population level by means of cosinor analysis using a linear mixed-effect approach. The mixed-effects analysis indicated increased refractoriness relative to baseline for all drugs. An additional decrease in circadian variation for parameters representing conduction delay was observed for the β -blockers. This indicates that the two drug types have quantifiable differences in their effects on AV-nodal conduction properties. These differences could be important in treatment outcome, and thus quantifying them could assist in treatment selection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Karlsson, Wallman, Platonov, Ulimoen and Sandberg.)

Background: The autonomic nervous system (ANS) is known as a potent modulator of the initiation and perpetuation of atrial fibrillation (AF), hence information about ANS activity during AF may improve treatment strategy. Respiratory induced ANS variation in the f-waves of the ECG may provide such information. Objective: This paper proposes a novel approach for improved estimation of such respiratory induced variations and investigates the impact of deep breathing on the f-wave frequency in AF patients. Methods: A harmonic model is fitted to the f-wave signal to estimate a high-resolution f-wave frequency trend, and an orthogonal subspace projection approach is employed to quantify variations in the frequency trend that are linearly related to respiration using an ECG-derived respiration signal. The performance of the proposed approach is evaluated and compared to that of a previously proposed bandpass filtering approach using simulated f-wave signals. Further, the proposed approach is applied to analyze ECG data recorded for 5 min during baseline and 1 min deep breathing from 28 AF patients from the Swedish cardiopulmonary bioimage study (SCAPIS). Results: The simulation results show that the estimates of respiratory variations obtained using the proposed approach are more accurate than estimates obtained using the previous approach. Results from the analysis of SCAPIS data show no significant differences between baseline and deep breathing in heart rate (75.5 ± 22.9 vs. 74 ± 22.3) bpm, atrial fibrillation rate (6.93 ± 1.18 vs. 6.94 ± 0.66) Hz and respiratory f-wave frequency variations (0.130 ± 0.042 vs. 0.130 ± 0.034) Hz. However, individual variations are large with changes in heart rate and atrial fibrillatory rate in response to deep breathing ranging from -9% to +5% and -8% to +6%, respectively and there is a weak correlation between changes in heart rate and changes in atrial fibrillatory rate ( r = 0.38, p < 0.03). Conclusion: Respiratory induced f-wave frequency variations were observed at baseline and during deep breathing. No significant changes in the magnitude of these variations in response to deep breathing was observed in the present study population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abdollahpur, Engström, Platonov and Sandberg.)

The response to atrial fibrillation (AF) treatment is differing widely among patients, and a better understanding of the factors that contribute to these differences is needed. One important factor may be differences in the autonomic nervous system (ANS) activity. The atrioventricular (AV) node plays an important role during AF in modulating heart rate. To study the effect of the ANS-induced activity on the AV nodal function in AF, mathematical modelling is a valuable tool. In this study, we present an extended AV node model that incorporates changes in autonomic tone. The extension was guided by a distribution-based sensitivity analysis and incorporates the ANS-induced changes in the refractoriness and conduction delay. Simulated RR series from the extended model driven by atrial impulse series obtained from clinical tilt test data were qualitatively evaluated against clinical RR series in terms of heart rate, RR series variability and RR series irregularity. The changes to the RR series characteristics during head-down tilt were replicated by a 10% decrease in conduction delay, while the changes during head-up tilt were replicated by a 5% decrease in the refractory period and a 10% decrease in the conduction delay. We demonstrate that the model extension is needed to replicate ANS-induced changes during tilt, indicating that the changes in RR series characteristics could not be explained by changes in atrial activity alone., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Plappert, Wallman, Abdollahpur, Platonov, Östenson and Sandberg.)

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is predominantly caused by desmosomal genetic variants, and clinical hallmarks include arrhythmias and systolic dysfunction. We aimed at studying the impact of the implicated gene(s) on the disease course., Methods: The Nordic ARVC Registry holds data on a multinational cohort of ARVC families. The effects of genotype on electrocardiographic features, imaging findings and clinical events were analysed., Results: We evaluated 419 patients (55% men), with a mean follow-up of 11.2±7.4 years. A pathogenic desmosomal variant was identified in 62% of the 230 families: PKP2 in 41%, DSG2 in 13%, DSP in 7% and DSC2 in 3%. Reduced left ventricular ejection fraction (LVEF) ≤45% on cardiac MRI was more frequent among patients with DSC2 / DSG2 / DSP than PKP2 ARVC (27% vs 4%, p<0.01). In contrast, in Cox regression modelling of patients with definite ARVC, we found a higher risk of arrhythmias among PKP2 than DSC2 / DSG2 / DSP carriers: HR 0.25 (0.10-0.68, p<0.01) for atrial fibrillation/flutter, HR 0.67 (0.44-1.0, p=0.06) for ventricular arrhythmias and HR 0.63 (0.42-0.95, p<0.05) for any arrhythmia. Gene-negative patients had an intermediate risk (16%) of LVEF ≤45% and a risk of the combined arrhythmic endpoint comparable with DSC2 / DSG2 / DSP carriers. Male sex was a risk factor for both arrhythmias and reduced LVEF across all genotype groups (p<0.01)., Conclusion: In this large cohort of ARVC families with long-term follow-up, we found PKP2 genotype to be more arrhythmic than DSC2 / DSG 2/ DSP or gene-negative carrier status, whereas reduced LVEF was mostly seen among DSC2 / DSG 2/ DSP carriers. Male sex was associated with a more severe phenotype., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients., Methods and Results: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.3% reduction of ICD placements with the same proportion of protected patients (P < 0.001)., Conclusion: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com)., Competing Interests: Conflict of interest: H.C. is a consultant for Medtronic Inc. and St. Jude Medical/Abbott. H.C. receives research support from Boston Scientific Corp. C.T. and C.A.J. receive salary support from this grant. C.A.J. has received funding for an invited lecture from Abbott. H.T. receives research support from Abbott. A.A.M.W. received a personal fee from Audentes 2017. A.M.S. received lecture honoraria from Boston Scientific Corp. S.L.Z. receives salary support as an advisor to Siemens Healthcare. D.P.J. is a consultant for Pfizer, GSK, and Blade Therapeutics, and receives research support from NIH, Eidos Therapeutics, and Array Biopharma. The rest of the authors have no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)