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1.	Walsh, Roddy, et al. (författare) Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls 2021 Ingår i: Genetics in Medicine. - : Nature Publishing Group. - 1098-3600 .- 1530-0366. ; 23:1, s. 47-58 Tidskriftsartikel (refereegranskat)abstract Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
2.	Bacharova, Ljuba, et al. (författare) ISE/ISHNE Expert Consensus Statement on ECG Diagnosis of Left Ventricular Hypertrophy : The Change of the Paradigm. The joint paper of the International Society of Electrocardiology and the International Society for Holter Monitoring and Noninvasive Electrocardiology 2023 Ingår i: Journal of Electrocardiology. - 0022-0736 .- 1532-8430. ; 81, s. 85-93 Forskningsöversikt (refereegranskat)abstract 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.
3.	Bacharova, Ljuba, et al. (författare) ISE/ISHNE expert consensus statement on the ECG diagnosis of left ventricular hypertrophy : The change of the paradigm 2023 Ingår i: Annals of Noninvasive Electrocardiology. - 1082-720X. ; 29:1, s. e13097- Tidskriftsartikel (refereegranskat)abstract 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.
4.	Bernikova, Olesya G., et al. (författare) ECG Markers of Acute Melatonin Treatment in a Porcine Model of Acute Myocardial Ischemia 2022 Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:19 Tidskriftsartikel (refereegranskat)abstract 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.
5.	Bernikova, Olesya G., et al. (författare) Prolonged repolarization in the early phase of ischemia is associated with ventricular fibrillation development in a porcine model 2023 Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 14 Tidskriftsartikel (refereegranskat)abstract 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.
6.	Bressi, Edoardo, et al. (författare) Arrhythmia Monitoring and Outcomes in Patients With Cardiac Sarcoidosis : Insights From the Cardiac Sarcoidosis Consortium 2022 Ingår i: Journal of the American Heart Association. - 2047-9980. ; 11:13 Tidskriftsartikel (refereegranskat)
7.	Christiansen, Morten K, et al. (författare) Incidence, Predictors, and Success of Ventricular Tachycardia Catheter Ablation in Arrhythmogenic Right Ventricular Cardiomyopathy (from the Nordic ARVC Registry). 2020 Ingår i: The American journal of cardiology. - : Elsevier BV. - 1879-1913 .- 0002-9149. ; 125:5, s. 803-811 Tidskriftsartikel (refereegranskat)abstract Catheter ablation may reduce ventricular tachycardia (VT) burden in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. However, little is known about factors predicting need for ablation. Therefore, we sought to investigate predictors and use of VT ablation and to evaluate the postprocedural outcome in ARVC patients. We studied 435 patients from the Nordic ARVC registry including 220 probands with definite ARVC according to the 2010 task force criteria and 215 mutation-carrying relatives identified through cascade screening. Patients were followed until first-time VT ablation, death, heart transplantation, or January 1st 2018. Additionally, patients undergoing VT ablation were further followed from the time of ablation for recurrent ventricular arrhythmias. The cumulative use of VT ablation was 4% (95% confidence interval [CI] 3% to 6%) and 11% (95% CI 8% to 15%) after 1 and 10 years. All procedures were performed in probands in whom cumulative use was 8% (95% CI 5% to 12%) and 20% (95% CI 15% to 26%). In adjusted analyses among probands, only young age predicted ablation. In patients undergoing ablation, risk of recurrent arrhythmias was 59% (95% CI 44% to 71%) and 74% (95% CI 59% to 84%) 1 and 5 years after the procedure. Despite high recurrence rates, the burden of ventricular arrhythmias was reduced after ablation (p=0.0042). Young age, use of several antiarrhythmic drugs and inducibility to VT after ablation were associated with an unfavorable outcome. In conclusion, twenty percent of ARVC probands developed a clinical indication for VT ablation within 10 years whereas mutation-carrying relatives were without such need. Although the burden of ventricular arrhythmias decreased after ablation, risk of recurrence was substantial.
8.	Lahrouchi, Najim, et al. (författare) Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome 2020 Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 142:4, s. 324-338 Tidskriftsartikel (refereegranskat)abstract Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. Methods: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P<5x10(-8)) nearNOS1AP,KCNQ1, andKLF12, and 1 missense variant inKCNE1(p.Asp85Asn) at the suggestive threshold (P<10(-6)). Heritability analyses showed that approximate to 15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (r(g)=0.40;P=3.2x10(-3)). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (P<10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (P<0.005). Conclusions: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.
9.	Myadam, Rahul, et al. (författare) Reply : Association of Adverse Events With the Different Diagnostic Schemes of Cardiac Sarcoidosis 2023 Ingår i: JACC: Clinical Electrophysiology. - 2405-500X. ; 9:12, s. 2662-2663 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
10.	Myadam, Rahul, et al. (författare) Risk of Adverse Outcomes Associated With Cardiac Sarcoidosis Diagnostic Schemes 2023 Ingår i: JACC: Clinical Electrophysiology. - 2405-500X. ; 9:8, s. 1719-1729 Tidskriftsartikel (refereegranskat)abstract 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.
11.	Sedova, Ksenia A, et al. (författare) Terminal T-wave inversion predicts reperfusion tachyarrhythmias in STEMI 2022 Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 71, s. 28-31 Tidskriftsartikel (refereegranskat)abstract INTRODUCTION: A reliable electrocardiographic predictor of ventricular fibrillation (VF) in patients with ST elevation myocardial infarction (STEMI) is lacking so far. Previous experimental/simulation study suggested a terminal T-wave inversion (TTWI) in ischemia-related ECG leads corresponding to anterior infarct localization as an independent predictor of reperfusion VF (rVF). This T-wave characteristic has never been tested as a rVF predictor in clinical settings. The aim of this study was to test if terminal T-wave inversion (TTWI) at admission ECG (before reperfusion) can serve as a predictor of ventricular fibrillation during reperfusion (rVF) in patients with anterior STEMI undergoing primary PCI.METHODS AND RESULTS: Study population included consecutive patients with anterior infarct localization admitted for primary PCI (n = 181, age 65 [57; 76] years, 66% male). Of those, 14 patients had rVF (rVF group, age 59 [47; 76] years, 64% male) and patients without rVF comprised the No-rVF group (n = 167, age 65 [57; 76] years, 66% male). Association of TTWI with rVF was analyzed using logistic regression analysis adjusted for relevant clinical and electrocardiographic covariates. The prevalence of TTWI in rVF group was 62% comparing to 23% in the No-rVF group, p = 0.005. TTWI was associated with increased risk of rVF (OR 5.51; 95% CI 1.70-17.89; p = 0.004) and remained a significant predictor after adjustment for age, gender, history of MI prior to index admission, VF before reperfusion, Tpeak-Tend, maximal ST elevation, and QRS duration (OR 23.49; 95% CI 3.14-175.91; p = 0.002).CONCLUSIONS: The terminal T-wave inversion in anterior leads before PCI independently predicted rVF in patients with anterior MI thus confirming the previous experimental/simulation findings.
12.	Tsvetkova, Alena S., et al. (författare) Contribution of Depolarization and Repolarization Changes to J-Wave Generation and Ventricular Fibrillation in Ischemia 2020 Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 11 Tidskriftsartikel (refereegranskat)abstract Background: Activation delay in ischemic myocardium has been found to contribute to J-wave appearance and to predict ventricular fibrillation (VF) in experimental myocardial infarction. However, the role of ischemia-related repolarization abnormalities in J-wave generation remains unclear. Objectives: The objective of our study was to assess a contribution of myocardial repolarization changes to J-wave generation in the body surface ECG and VF in a porcine acute myocardial infarction model. Methods: In 22 anesthetized pigs, myocardial ischemia was induced by occlusion of the left anterior descending coronary artery (LAD, n = 14) and right coronary artery (RCA, n = 8). Body surface ECGs were recorded simultaneously with intramyocardial unipolar electrograms led from flexible electrodes positioned across the left ventricular (LV) wall, interventricular septum (IVS), and right ventricular (RV) wall at apical, middle and basal levels of the ventricles (a total of 48 leads). Local activation times (ATs) and activation-repolarization intervals (ARIs, differences between dV/dt maximum during T-wave and dV/dt minimum during QRS) were measured. Results: J-waves appeared in left precordial leads (in 11 out of 14 animals with LAD occlusion) and right precordial leads (in six out of eight animals with RCA occlusion). During ischemic exposure, ATs prolonged, and the activation delay was associated with J-wave development (OR = 1.108 95% CI 1.072–1.144; p < 0.001) and VF incidence (OR = 1.039 95% CI 1.008–1.072; p = 0.015). ARIs shortened in the ischemic regions (in the IVS under LAD-occlusion and the lateral RV base under RCA-occlusion). The difference between maximal ARI in normal zones and ARI in the ischemic zones (ΔARI) was associated with J-wave appearance (OR = 1.025 95% CI 1.016–1.033, p < 0.001) independently of AT delay in multivariate logistic regression analysis. Conclusions: Both AT delay and increase of ΔARIs contributed to the development of J-wave in body surface ECG. However, only AT delay was associated with VF occurrence.
13.	Tsvetkova, Alena S., et al. (författare) Melatonin Prevents Early but Not Delayed Ventricular Fibrillation in the Experimental Porcine Model of Acute Ischemia 2020 Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 22:1 Tidskriftsartikel (refereegranskat)abstract Antiarrhythmic effects of melatonin have been demonstrated ex vivo and in rodent models, but its action in a clinically relevant large mammalian model remains largely unknown. Objectives of the present study were to evaluate electrophysiological and antiarrhythmic effects of melatonin in a porcine model of acute myocardial infarction. Myocardial ischemia was induced by 40-min coronary occlusion in 25 anesthetized pigs. After ischemia onset, 12 animals received melatonin (4 mg/kg). 48 intramyocardial electrograms were recorded from left ventricular wall and interventricular septum (IVS). In each lead, activation time (AT) and repolarization time (RT) were determined. During ischemia, ATs and dispersion of repolarization (DOR = RTmax - RTmin) increased reaching maximal values by 3-5 and 20-25 min, respectively. Ventricular fibrillation (VF) incidence demonstrated no relations to redox state markers and was associated with increased DOR and delayed ATs (specifically, in an IVS base, an area adjacent to the ischemic zone) (p = 0.031). Melatonin prevented AT increase in the IVS base, (p < 0.001) precluding development of early VF (1-5 min, p = 0.016). VF occurrence in the delayed phase (17-40 min) where DOR was maximal was not modified by melatonin. Thus, melatonin-related enhancement of activation prevented development of early VF in the myocardial infarction model.
14.	Abdollahpur, Mostafa, et al. (författare) A subspace projection approach to quantify respiratory variations in the f-wave frequency trend 2022 Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 13 Tidskriftsartikel (refereegranskat)abstract 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.
15.	Abdollahpur, Mostafa, et al. (författare) Respiratory Induced Modulation in f-Wave Characteristics During Atrial Fibrillation 2021 Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 12 Tidskriftsartikel (refereegranskat)abstract The autonomic nervous system (ANS) is an important factor in cardiac arrhythmia, and information about ANS activity during atrial fibrillation (AF) may contribute to personalized treatment. In this study we aim to quantify respiratory modulation in the f-wave frequency trend from resting ECG. First, an f-wave signal is extracted from the ECG by QRST cancelation. Second, an f-wave model is fitted to the f-wave signal to obtain a high resolution f-wave frequency trend and an index for signal quality control ((Formula presented.)). Third, respiratory modulation in the f-wave frequency trend is extracted by applying a narrow band-pass filter. The center frequency of the band-pass filter is determined by the respiration rate. Respiration rate is estimated from a surrogate respiration signal, obtained from the ECG using homomorphic filtering. Peak conditioned spectral averaging, where spectra of sufficient quality from different leads are averaged, is employed to obtain a robust estimate of the respiration rate. The envelope of the filtered f-wave frequency trend is used to quantify the magnitude of respiratory induced f-wave frequency modulation. The proposed methodology is evaluated using simulated f-wave signals obtained using a sinusoidal harmonic model. Results from simulated signals show that the magnitude of the respiratory modulation is accurately estimated, quantified by an error below 0.01 Hz, if the signal quality is sufficient ((Formula presented.)). The proposed method was applied to analyze ECG data from eight pacemaker patients with permanent AF recorded at baseline, during controlled respiration, and during controlled respiration after injection of atropine, respectively. The magnitude of the respiratory induce f-wave frequency modulation was 0.15 ± 0.01, 0.18 ± 0.02, and 0.17 ± 0.03 Hz during baseline, controlled respiration, and post-atropine, respectively. Our results suggest that parasympathetic regulation affects the magnitude of respiratory induced f-wave frequency modulation.
16.	Abdollahpur, Mostafa, et al. (författare) Respiratory Modulation in Permanent Atrial Fibrillation 2020 Ingår i: 2020 Computing in Cardiology, CinC 2020. - 2325-8861 .- 2325-887X. - 9781728173825 ; 2020-September Konferensbidrag (refereegranskat)abstract Several studies have shown that the autonomic nervous system (ANS) can induce changes during atrial fibrillation (AF). There is currently a lack of methods for quantifying ANS induced variations during AF. The purpose of this study is to quantify respiratory induced modulation in the f-wave frequency trend. Following qrst-cancellation, the local f-wave frequency is estimated by fitting a harmonic f-wave model signal and a quality index (SQI) is computed based on the model fit. The resulting frequency trend is filtered using a narrow bandpass filter with a center frequency corresponding to the local respiration rate. The magnitude of the respiratory induced f-wave frequency modulation is estimated by the envelope of the filtered frequency trend. The performance of the method is validated using simulations and the method is applied to analyze ECG data from eight patients with permanent AF recorded during 0.125 Hz frequency controlled respiration before and after the full vagal blockade, respectively. Results from simulated data show the magnitude of the respiratory induced f-wave frequency modulation can be estimated with an error of less than = 0.005Hz if the SQI is above 0.45. The signal quality was sufficient for analysis in 7 out of 8 patients. In 4 patients the magnitude decreased and in 3 patients there was no change.
17.	Attia, Zachi I., et al. (författare) Rapid Exclusion of COVID Infection With the Artificial Intelligence Electrocardiogram 2021 Ingår i: Mayo Clinic proceedings. - : ELSEVIER SCIENCE INC. - 0025-6196 .- 1942-5546. ; 96:8, s. 2081-2094 Tidskriftsartikel (refereegranskat)abstract Objective: To rapidly exclude severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using artificial intelligence applied to the electrocardiogram (ECG). Methods: A global, volunteer consortium from 4 continents identified patients with ECGs obtained around the time of polymerase chain reaction-confirmed COVID-19 diagnosis and age- and sex-matched controls from the same sites. Clinical characteristics, polymerase chain reaction results, and raw electrocardiographic data were collected. A convolutional neural network was trained using 26,153 ECGs (33.2% COVID positive), validated with 3826 ECGs (33.3% positive), and tested on 7870 ECGs not included in other sets (32.7% positive). Performance under different prevalence values was tested by adding control ECGs from a single high-volume site. Results: The area under the curve for detection of acute COVID-19 infection in the test group was 0.767 (95% CI, 0.756 to 0.778; sensitivity, 98%; specificity, 10%; positive predictive value, 37%; negative predictive value, 91%). To more accurately reflect a real-world population, 50,905 normal controls were added to adjust the COVID prevalence to approximately 5% (2657/58,555), resulting in an area under the curve of 0.780 (95% CI, 0.771 to 0.790) with a specificity of 12.1% and a negative predictive value of 99.2%. Conclusion: Infection with SARS-CoV-2 results in electrocardiographic changes that permit the artificial intelligence-enhanced ECG to be used as a rapid screening test with a high negative predictive value (99.2%). This may permit the development of electrocardiography-based tools to rapidly screen individuals for pandemic control. (C) 2021 Mayo Foundation Medical Education and Research
18.	Baturova, Maria A., et al. (författare) Atrial fibrillation as a clinical characteristic of arrhythmogenic right ventricular cardiomyopathy : Experience from the Nordic ARVC Registry 2020 Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 298, s. 39-43 Tidskriftsartikel (refereegranskat)abstract Background: Recent studies in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients have drawn attention to atrial fibrillation (AF) as an arrhythmic manifestation of ARVC and as an indicator of atrial involvement in the disease progression. We aimed to assess the prevalence of AF in the Scandinavian cohort of ARVC patients and to evaluate its association with disease clinical manifestations. Methods: Study sample comprised of 293 definite ARVC patients by 2010 Task Force criteria (TFC2010) and 141 genotype-positive family members (total n = 434, 43% females, median age at ARVC diagnosis 41 years [interquartile range (IQR) 28–52 years]). ARVC diagnostic score was calculated as the sum of major (2 points) and minor (1 point) criteria in all categories of the TFC2010. Results: AF was diagnosed in 42 patients (10%): in 41 patients with definite ARVC diagnosis (14%) vs in one genotype-positive family member (1%), p < 0.001. The median age at AF onset was 51 (IQR 38–58) years. The prevalence of AF was related to the ARVC diagnostic score: it significantly increased starting with the diagnostic score 4 (2% in those with score 3 vs 13% in those with score 4, p = 0.023) and increased further with increased diagnostic score (Somer's d value is 0.074, p < 0.001). Conclusion: AF is seen in 14% of definite ARVC patients and is related to the severity of disease phenotype thus suggesting AF being an arrhythmic manifestation of this cardiomyopathy indicating atrial myocardial involvement in the disease progression.
19.	Baturova, Maria A., et al. (författare) Evolution of P-wave indices during long-term follow-up as markers of atrial substrate progression in arrhythmogenic right ventricular cardiomyopathy 2021 Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 23:Supplement_1, s. i29-i37 Tidskriftsartikel (refereegranskat)abstract AIMS: Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) have increased prevalence of atrial arrhythmias indicating atrial involvement in the disease. We aimed to assess the long-term evolution of P-wave indices as electrocardiographic (ECG) markers of atrial substrate during ARVC progression.METHODS AND RESULTS: We included 100 patients with a definite ARVC diagnosis according to 2010 Task Force criteria [34% females, median age 41 (inter-quartile range 30-55) years]. All available sinus rhythm ECGs (n = 1504) were extracted from the regional electronic ECG databases and automatically processed using Glasgow algorithm. P-wave duration, P-wave area, P-wave frontal axis, and prevalence of abnormal P terminal force in lead V1 (aPTF-V1) were assessed and compared at ARVC diagnosis, 10 years before and up to 15 years after diagnosis.Prior to ARVC diagnosis, none of the P-wave indices differed significantly from the data at ARVC diagnosis. After ascertainment of ARVC diagnosis, P-wave area in lead V1 decreased from -1 to -30 µV ms at 5 years (P = 0.002). P-wave area in lead V2 decreased from 82 µV ms at ARVC diagnosis to 42 µV ms 10 years after ARVC diagnosis (P = 0.006). The prevalence of aPTF-V1 increased from 5% at ARVC diagnosis to 18% by the 15th year of follow-up (P = 0.004). P-wave duration and frontal axis did not change during disease progression.CONCLUSION: Initial ARVC progression was associated with P-wave flattening in right precordial leads and in later disease stages an increased prevalence of aPTF-V1 was seen.
20.	Baturova, Maria A., et al. (författare) P-wave characteristics as electrocardiographic markers of atrial abnormality in prediction of incident atrial fibrillation – The Malmö Preventive Project 2024 Ingår i: Journal of Electrocardiology. - 0022-0736 .- 1532-8430. ; 82, s. 125-130 Tidskriftsartikel (refereegranskat)abstract 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.
21.	Buhl, Rikke, et al. (författare) Atrial fibrillatory rate as predictor of recurrence of atrial fibrillation in horses treated medically or with electrical cardioversion 2022 Ingår i: Equine Veterinary Journal. - : Wiley. - 0425-1644 .- 2042-3306. ; 54:6, s. 1013-1022 Tidskriftsartikel (refereegranskat)abstract 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.
22.	Cadrin-Tourigny, Julia, et al. (författare) A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy 2022 Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 43:32, s. 1-9 Tidskriftsartikel (refereegranskat)abstract 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).
23.	Cadrin-Tourigny, Julia, et al. (författare) Sudden Cardiac Death Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy : A Multinational Collaboration 2021 Ingår i: Circulation: Arrhythmia and Electrophysiology. - : Lippincott Williams & Wilkins. - 1941-3149 .- 1941-3084. ; 14:1 Tidskriftsartikel (refereegranskat)abstract Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in patients with ARVC. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD. Methods: We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 prespecified clinical predictors with LTVA (SCD, aborted SCD, sustained, or implantable cardioverter-defibrillator treated ventricular tachycardia >250 beats per minute) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (≥30s, hemodynamically unstable, or implantable cardioverter-defibrillator treated ventricular tachycardia; or aborted SCD), syncope, 24-hour premature ventricular complexes count, the number of anterior and inferior leads with T-wave inversion, left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping. Results: A total of 864 patients with definite ARVC (40±16 years; 53% male) were included. Over 5.75 years (interquartile range, 2.77-10.58) of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 prespecified clinical predictors, only 4 (younger age, male sex, premature ventricular complex count, and number of leads with T-wave inversion) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA (P=0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI, 0.69-0.80) and calibration slope of 0.95 (95% CI, 0.94-0.98) indicating minimal over-optimism. Conclusions: LTVA events in patients with ARVC can be predicted by a novel simple prediction model using only 4 clinical predictors. Prior sustained VA and the extent of functional heart disease are not associated with subsequent LTVA events.
24.	Carrick, Richard T., et al. (författare) Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe 2024 Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. Tidskriftsartikel (refereegranskat)abstract 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.
25.	Chaudhry, Uzma, et al. (författare) Vectorcardiography Findings Are Associated with Recurrent Ventricular Arrhythmias and Mortality in Patients with Heart Failure Treated with Implantable Cardioverter-Defibrillator Device 2020 Ingår i: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 145:12, s. 784-794 Tidskriftsartikel (refereegranskat)abstract Background: There is a need for refined risk stratification of sudden cardiac death and prediction of ventricular arrhythmias to correctly identify patients who are expected to benefit the most from implantable cardioverter-defibrillator (ICD) therapy. Methods: We conducted a registry-based retrospective observational study on patients with either ischemic (ICMP) or nonischemic dilated cardiomyopathy (NICMP) treated with ICD between 2002 and 2013 at a tertiary referral center. We evaluated 3 vectorcardiography (VCG) indices; spatial QRS-T angle, QRS vector magnitude (QRSvm), and T-wave vector magnitude (Twvm), and their association with all-cause mortality and ventricular arrhythmias. The VCG indices were automatically computed from resting 12-lead electrocardiograms before ICD implantation. Results: 178 patients were included in the study; 53.4% had ICMP, 79.2% were male, and mean ejection fraction was 27.4%. During the follow-up (median 89 months), 40 patients (23%) died; 31% had appropriate ICD therapy. In multivariate analysis with dichotomized variables, QRS-T angle >152° and Twvm <0.38 mV were significantly associated with increased mortality: HR 2.64 (95% CI 1.14-6.12, p = 0.02) and HR 5.30 (95% CI 2.31-12.11, p < 0.001), respectively. QRSvm <1.54 mV was borderline significant with mortality outcome (p = 0.10). The composite score of all 3 VCG indices, a score of 3, conferred an increased risk of mortality (including heart failure mortality) in multivariate analysis: HR 13.80 (95% CI 3.44-55.39, p < 0.001). Conclusion: The spatial QRS-T angle and Twvm are emerging VCG indices which are independently associated with mortality in patients with reduced left ventricular ejection fraction due to ICMP or NICMP. Using a composite score of all 3 vector indices, a maximum score was associated with poor long-term survival.
26.	Chen, Lin Yee, et al. (författare) P Wave Parameters and Indices : A Critical Appraisal of Clinical Utility, Challenges, and Future Research—A Consensus Document Endorsed by the International Society of Electrocardiology and the International Society for Holter and Noninvasive Electrocardiology 2022 Ingår i: Circulation: Arrhythmia and Electrophysiology. - 1941-3149. ; 15:4, s. 010435-010435 Forskningsöversikt (refereegranskat)abstract Atrial cardiomyopathy, characterized by abnormalities in atrial structure and function, is associated with increased risk of adverse cardiovascular and neurocognitive outcomes, independent of atrial fibrillation. There exists a critical unmet need for a clinical tool that is cost-effective, easy to use, and that can diagnose atrial cardiomyopathy. P wave parameters (PWPs) reflect underlying atrial structure, size, and electrical activation; alterations in these factors manifest as abnormalities in PWPs that can be readily ascertained from a standard 12-lead ECG and potentially be used to aid clinical decision-making. PWPs include P wave duration, interatrial block, P wave terminal force in V1, P wave axis, P wave voltage, P wave area, and P wave dispersion. PWPs can be combined to yield an index (P wave index), such as the morphology-voltage-P-wave duration ECG risk score. Abnormal PWPs have been shown in population-based cohort studies to be independently associated with higher risks of atrial fibrillation, ischemic stroke, sudden cardiac death, and dementia. Additionally, PWPs, either individually or in combination (as a P wave index), have been reported to enhance prediction of atrial fibrillation or ischemic stroke. To facilitate translation of PWPs to routine clinical practice, additional work is needed to standardize measurement of PWPs (eg, via semiautomated or automated measurement), confirm their reliability and predictive value, leverage novel approaches (eg, wavelet analysis of P waves and machine learning algorithms), and finally, define the risk-benefit ratio of specific interventions in high-risk individuals. Our ultimate goal is to repurpose the ubiquitous 12-lead ECG to advance the study, diagnosis, and treatment of atrial cardiomyopathy, thus overcoming critical challenges in prevention of cardiovascular disease and dementia.
27.	Christensen, Alex Hørby, et al. (författare) Complications of implantable cardioverter-defibrillator treatment in arrhythmogenic right ventricular cardiomyopathy 2022 Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 24:2, s. 306-312 Tidskriftsartikel (refereegranskat)abstract Aims: Treatment with implantable cardioverter-defibrillators (ICD) is a cornerstone for prevention of sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed at describing the complications associated with ICD treatment in a multinational cohort with long-term follow-up. Methods and results: The Nordic ARVC registry was established in 2010 and encompasses a large multinational cohort of ARVC patients, including their clinical characteristics, treatment, and events during follow-up. We included 299 patients (66% males, median age 41 years). During a median follow-up of 10.6 years, 124 (41%) patients experienced appropriate ICD shock therapy, 28 (9%) experienced inappropriate shocks, 82 (27%) had a complication requiring surgery (mainly lead-related, n = 75), and 99 (33%) patients experienced the combined endpoint of either an inappropriate shock or a surgical complication. The crude rate of first inappropriate shock was 3.4% during the first year after implantation but decreased after the first year and plateaued over time. Contrary, the risk of a complication requiring surgery was 5.5% the first year and remained high throughout the study period. The combined risk of any complication was 7.9% the first year. In multivariate cox regression, presence of atrial fibrillation/flutter was a risk factor for inappropriate shock (P < 0.05), whereas sex, age at implant, and device type were not (all P > 0.05). Conclusion: Forty-one percent of ARVC patients treated with ICD experienced potentially life-saving ICD therapy during long-term follow-up. A third of the patients experienced a complication during follow-up with lead-related complications constituting the vast majority.
28.	Christensen, Alex Hörby, et al. (författare) Genotype-phenotype correlation in arrhythmogenic right ventricular cardiomyopathy-risk of arrhythmias and heart failure. 2021 Ingår i: Journal of medical genetics. - : BMJ PUBLISHING GROUP. - 1468-6244 .- 0022-2593. Tidskriftsartikel (refereegranskat)abstract 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.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.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).In this large cohort of ARVC families with long-term follow-up, we found PKP2 genotype to be more arrhythmic than DSC2/DSG2/DSP or gene-negative carrier status, whereas reduced LVEF was mostly seen among DSC2/DSG2/DSP carriers. Male sex was associated with a more severe phenotype.
29.	Christensen, Alex Horby, et al. (författare) Genotype-phenotype correlation in arrhythmogenic right ventricular cardiomyopathy-risk of arrhythmias and heart failure 2022 Ingår i: Journal of Medical Genetics. - : BMJ PUBLISHING GROUP. - 0022-2593 .- 1468-6244. ; 59:9, s. 858-864 Tidskriftsartikel (refereegranskat)abstract 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/DSG2/DSP or gene-negative carrier status, whereas reduced LVEF was mostly seen among DSC2/DSG2/DSP carriers. Male sex was associated with a more severe phenotype.
30.	Corrado, Domenico, et al. (författare) Arrhythmogenic right ventricular cardiomyopathy : Evaluation of the current diagnostic criteria and differential diagnosis 2020 Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 41:14, s. 1414-1427 Forskningsöversikt (refereegranskat)
31.	De Groot, Natasja M.S., et al. (författare) Critical appraisal of technologies to assess electrical activity during atrial fibrillation : a position paper from the European Heart Rhythm Association and European Society of Cardiology Working Group on eCardiology in collaboration with the Heart Rhythm Society, Asia Pacific Heart Rhythm Society, Latin American Heart Rhythm Society and Computing in Cardiology 2022 Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129. ; 24:2, s. 313-330 Forskningsöversikt (refereegranskat)abstract We aim to provide a critical appraisal of basic concepts underlying signal recording and processing technologies applied for (i) atrial fibrillation (AF) mapping to unravel AF mechanisms and/or identifying target sites for AF therapy and (ii) AF detection, to optimize usage of technologies, stimulate research aimed at closing knowledge gaps, and developing ideal AF recording and processing technologies. Recording and processing techniques for assessment of electrical activity during AF essential for diagnosis and guiding ablative therapy including body surface electrocardiograms (ECG) and endo- or epicardial electrograms (EGM) are evaluated. Discussion of (i) differences in uni-, bi-, and multi-polar (omnipolar/Laplacian) recording modes, (ii) impact of recording technologies on EGM morphology, (iii) global or local mapping using various types of EGM involving signal processing techniques including isochronal-, voltage- fractionation-, dipole density-, and rotor mapping, enabling derivation of parameters like atrial rate, entropy, conduction velocity/direction, (iv) value of epicardial and optical mapping, (v) AF detection by cardiac implantable electronic devices containing various detection algorithms applicable to stored EGMs, (vi) contribution of machine learning (ML) to further improvement of signals processing technologies. Recording and processing of EGM (or ECG) are the cornerstones of (body surface) mapping of AF. Currently available AF recording and processing technologies are mainly restricted to specific applications or have technological limitations. Improvements in AF mapping by obtaining highest fidelity source signals (e.g. catheter-electrode combinations) for signal processing (e.g. filtering, digitization, and noise elimination) is of utmost importance. Novel acquisition instruments (multi-polar catheters combined with improved physical modelling and ML techniques) will enable enhanced and automated interpretation of EGM recordings in the near future.
32.	Demidova, Marina M., et al. (författare) Early repolarization pattern on ECG recorded before the acute coronary event does not predict ventricular fibrillation during ST-elevation myocardial infarction 2020 Ingår i: Heart Rhythm. - : Elsevier BV. - 1547-5271. ; 17:4, s. 629-636 Tidskriftsartikel (refereegranskat)abstract Background: Generally considered benign, electrocardiographic (ECG) early repolarization (ER) pattern was claimed to be an indicator of increased susceptibility to ventricular arrhythmias during acute ischemia. Objective: The purpose of this study was to assess in a nonselected population whether ER pattern documented before ST-elevation myocardial infarction (STEMI) is associated with risk of hemodynamically unstable ventricular tachycardia (VT) or ventricular fibrillation (VF) during acute STEMI. Methods: For STEMI patients admitted for primary percutaneous coronary intervention from 2007–2010, the latest ECGs recorded before STEMI were exported in digital format. After excluding ECGs with paced rhythm and QRS duration ≥120 ms, the remaining ECGs were processed using the Glasgow algorithm allowing automatic ER detection. The association between ER pattern and VT/VF during the first 48 hours of STEMI was tested using logistic regression. Results: ECGs recorded before STEMI were available for 1584 patients. Of these patients, 124 did not meet inclusion criteria, leaving 1460 patients available for analysis (age 68 ± 12 years; 67% male). ER pattern was present in 272 patients (18.6%; ER+ group). ER+ and ER– groups did not differ with regard to clinical characteristics. VT/VF during the first 48 hours of STEMI occurred in 19 ER+ (7.0%) and 105 ER– patients (8.8%; P =.398). ER was not associated with any VT/VF (odds ratio [OR] 0.78; 95% confidence interval [CI] 0.47–1.29; P =.324); VT/VF before reperfusion (OR 0.48; 95% CI 0.23–1.001; P =.051); or reperfusion-related VT/VF (OR 1.28; 95% CI 0.55–3.01; P =.569). Conclusion: In a nonselected population of STEMI patients, the ER pattern on ECG recorded before the acute coronary event was not associated with VT/VF during the first 48 hours of STEMI.
33.	Demidova, Marina M., et al. (författare) J wave is an underestimated ECG marker of risk in acute ischemia 2021 Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 0022-0736. ; 66, s. 5-5 Tidskriftsartikel (refereegranskat)
34.	Demidova, Marina M., et al. (författare) Prognostic value of early sustained ventricular arrhythmias in ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention : A substudy of VALIDATE-SWEDEHEART trial 2023 Ingår i: Heart rhythm O2. - : Elsevier. - 2666-5018. ; 4:3, s. 200-206 Tidskriftsartikel (refereegranskat)abstract 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.
35.	Demidova, Marina M., et al. (författare) Relation of Early Monomorphic Ventricular Tachycardia to Long-Term Mortality in ST-Elevation Myocardial Infarction 2022 Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 163, s. 13-19 Tidskriftsartikel (refereegranskat)abstract Early ventricular tachycardia (VT) and ventricular fibrillation (VF) are associated with increased in-hospital mortality but do not influence the long-term prognosis in ST-elevation myocardial infarction (STEMI). Recent data advocate a differential approach to the type of arrhythmia and indicate long-term mortality hazard associated with monomorphic VT. We aimed to evaluate the prognostic value of early monomorphic VT compared to nonmonomorphic VT/VF in a nonselected cohort of STEMI patients. Consecutive STEMI patients admitted for primary percutaneous coronary intervention from 2007 to 2010 were included. Clinical characteristics were obtained from the Swedish national SWEDEHEART registry. The occurrence and type of early VT/VF were verified in medical records. All-cause mortality 8 years after STEMI was assessed using the Swedish Cause of Death Register. A total of 2,277 STEMI patients were included (age 66 ± 12 years, 70% male), among them 35 (1.5%) with early monomorphic VT and 115 (5.1%) with nonmonomorphic VT/VF. Patients with monomorphic VT had similar clinical characteristics compared to those with nonmonomorphic VT/VF. In total, 22 patients (63%) with monomorphic VT and 43 (37%) with nonmonomorphic VT/VF died by 8 years of follow-up (p = 0.011). Monomorphic VT was associated with a higher risk of all-cause mortality compared to nonmonomorphic VT/VF in univariate analysis (HR 2.03, 95% CI 1.21 to 3.39, p = 0.007) and after adjustment for age and history of myocardial infarction (MI) (HR 1.74, 95% CI 1.02 to 2.97, p = 0.041). Early monomorphic VT in STEMI is associated with a higher risk of all-cause mortality compared to nonmonomorphic VT/VF and deserves further studies to refine risk stratification strategies.
36.	Demidova, Marina M., et al. (författare) Ventricular arrhythmias during ST-segment elevation myocardial infarction and arrhythmic complications during recurrent ischaemic events 2024 Ingår i: European Heart Journal. - 0195-668X. ; 45:5, s. 393-395 Tidskriftsartikel (refereegranskat)
37.	Engström, Gunnar, et al. (författare) Cardiovagal Function Measured by the Deep Breathing Test : Relationships With Coronary Atherosclerosis 2022 Ingår i: Journal of the American Heart Association. - 2047-9980. ; 11:7 Tidskriftsartikel (refereegranskat)abstract Background The cardiovagal function can be assessed by quantification of respiratory sinus arrhythmia (RSA) during a deep breathing test. However, population studies of RSA and coronary atherosclerosis are lacking. This population-based study examined the relationship between RSA during deep breathing and coronary atherosclerosis, assessed by coronary artery calcium score (CACS). Methods and Results SCAPIS (Swedish Cardiopulmonary Bioimage Study) randomly invited men and women aged 50 to 64 years from the general population. CACS was obtained from computed tomography scanning, and deep breathing tests were performed in 4654 individuals. Expiration-inspiration differences (E-Is) of heart rates were calculated, and reduced RSA was defined as E-I in the lowest decile of the population. The relationship between reduced RSA and CACS (CACS≥100 or CACS≥300) was calculated using multivariable-adjusted logistic regression. The proportion of CACS≥100 was 24% in the lowest decile of E-I and 12% in individuals with E-I above the lowest decile (P<0.001), and the proportion of CACS≥300 was 12% and 4.8%, respectively (P<0.001). The adjusted odds ratio (OR) for CACS≥100 was 1.42 (95% CI, 1.10-1.84) and the adjusted OR for CACS≥300 was 1.62 (95% CI, 1.15-2.28), when comparing the lowest E-I decile with deciles 2 to 10. Adjusted ORs per 1 SD lower E-I were 1.17 (P=0.001) for CACS≥100 and 1.28 (P=0.001) for CACS≥300. Conclusions Low RSA during deep breathing is associated with increased coronary atherosclerosis as assessed by CACS, independently of traditional cardiovascular risk factors. Cardiovagal dysfunction could be a prevalent and modifiable risk factor for coronary atherosclerosis in the general population.
38.	Eranti, Antti, et al. (författare) Orthogonal P-wave morphology, conventional P-wave indices, and the risk of atrial fibrillation in the general population using data from the Finnish Hospital Discharge Register 2020 Ingår i: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. - : Oxford University Press (OUP). - 1532-2092. ; 22:8, s. 1173-1181 Tidskriftsartikel (refereegranskat)abstract AIMS: Identifying subjects at high and low risk of atrial fibrillation (AF) is of interest. This study aims to assess the risk of AF associated with electrocardiographic (ECG) markers linked to atrial fibrosis: P-wave prolongation, 3rd-degree interatrial block, P-terminal force in lead V1, and orthogonal P-wave morphology. METHODS AND RESULTS: P-wave parameters were assessed in a representative Finnish population sample aged ≥30 years (n = 7217, 46.0% male, mean age 51.4 years). Subjects (n = 5489) with a readable ECG including the orthogonal leads, sinus rhythm, and a predefined orthogonal P-wave morphology type [positive in leads X and Y and either negative (Type 1) or ± biphasic (Type 2) in lead Z; Type 3 defined as positive in lead X and ± biphasic in lead Y], were followed 10 years from the baseline examinations (performed 1978-80). Subjects discharged with AF diagnosis after any-cause hospitalization (n = 124) were defined as having developed AF. Third-degree interatrial block was defined as P-wave ≥120 ms and the presence of ≥2 ± biphasic P waves in the inferior leads. Hazard ratios (HRs) and confidence intervals (CIs) were assessed with Cox models. Third-degree interatrial block (n = 103, HR 3.18, 95% CI 1.66-6.13; P = 0.001) and Type 3 morphology (n = 216, HR 3.01, 95% CI 1.66-5.45; P < 0.001) were independently associated with the risk of hospitalization with AF. Subjects with P-wave <110 ms and Type 1 morphology (n = 2074) were at low risk (HR 0.46, 95% CI 0.26-0.83; P = 0.006), compared to the rest of the subjects. CONCLUSION: P-wave parameters associate with the risk of hospitalization with AF.
39.	Gasperetti, Alessio, et al. (författare) Efficacy of Catheter Ablation for Atrial Arrhythmias in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy - A Multicenter Study 2021 Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 10:21 Tidskriftsartikel (refereegranskat)abstract Background: Atrial arrhythmias are present in up to 20% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Catheter ablation (CA) is an effective treatment for atrial arrhythmias in the general population. Data regarding CA for atrial arrhythmias in ARVC are scarce. Objective: To assess the safety and efficacy of CA for atrial arrhythmias in patients with ARVC. Methods: In this international collaborative effort, all patients with a definite diagnosis of ARVC undergoing CA for atrial fibrillation (AF), focal atrial tachycardia (AT), or cavotricuspid isthmus (CTI)-dependent atrial flutter (AFl) were extracted from twelve ARVC registries. Demographic, periprocedural, and long-term arrhythmic outcome data were collected. Results: Thirty-seven patients were enrolled in the study (age 50.2 & PLUSMN; 16.6 years, male 84%, CHA(2)DS(2)VASc 1 (1,2), HAS-BLED 0 (0-2)). The arrhythmia leading to CA was AF in 23 (62%), focal left AT in 5 (14%), and CTI-dependent AFl in 9 (24%). Acute procedural success was achieved in all procedures but one (n = 1 focal left AT; 97% acute success). The median follow-up period was 27 (13-67) months, and 96%, 74%, and 61% of patients undergoing AF ablation were free from any atrial arrhythmia recurrence after a single procedure at 6 months, 12 months, and last follow-up, respectively. After focal AT ablation, freedom from atrial arrhythmia recurrence was 80%, 80%, and 60% at 6 months, 12 months, and last follow-up, respectively. All patients undergoing CTI ablation were free from atrial arrhythmia recurrences at 6 months, with 89% single-procedural arrhythmic freedom at last follow-up. One major complication (2.7%; PV stenosis requiring PV stenting) occurred. Conclusions: CA is safe and effective in managing atrial arrhythmias in patients with ARVC, with success rates comparable to the general population.
40.	Gasperetti, Alessio, et al. (författare) Programmed Ventricular Stimulation as an Additional Primary Prevention Risk Stratification Tool in Arrhythmogenic Right Ventricular Cardiomyopathy : A Multinational Study 2022 Ingår i: Circulation. - : Lippincott, Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 146:19, s. 1434-1443 Tidskriftsartikel (refereegranskat)abstract 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.
41.	Henriksson, Mikael, et al. (författare) Modeling and Estimation of Temporal Episode Patterns in Paroxysmal Atrial Fibrillation 2021 Ingår i: IEEE Transactions on Biomedical Engineering. - 0018-9294. ; 68:1, s. 319-329 Tidskriftsartikel (refereegranskat)abstract Objective: The present study proposes a model-based, statistical approach to characterizing episode patterns in paroxysmal atrial fibrillation (AF). Thanks to the rapid advancement of noninvasive monitoring technology, the proposed approach should become increasingly relevant in clinical practice. Methods: History-dependent point process modeling is employed to characterize AF episode patterns, using a novel alternating, bivariate Hawkes self-exciting model. In addition, a modified version of a recently proposed statistical model to simulate AF progression throughout a lifetime is considered, involving non-Markovian rhythm switching and survival functions. For each model, the maximum likelihood estimator is derived and used to find the model parameters from observed data. Results: Using three databases with a total of 59 long-term ECG recordings, the goodness-of-fit analysis demonstrates that the proposed alternating, bivariate Hawkes model fits SR-to-AF transitions in 40 recordings and AF-to-SR transitions in 51; the corresponding numbers for the AF model with non-Markovian rhythm switching are 40 and 11, respectively. Moreover, the results indicate that the model parameters related to AF episode clustering, i.e., aggregation of temporal AF episodes, provide information complementary to the well-known clinical parameter AF burden. Conclusion: Point process modeling provides a detailed characterization of the occurrence pattern of AF episodes that may improve the understanding of arrhythmia progression.
42.	Holmqvist, Fredrik, et al. (författare) Study of ECG-derived atrial fibrillatory rate for prediction of the outcome of cardioversion of short duration atrial fibrillation (CASAF) 2023 Ingår i: Journal of Electrocardiology. - 0022-0736. ; 81, s. 20-22 Tidskriftsartikel (refereegranskat)abstract 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).
43.	Jacobsson, Jonatan, et al. (författare) Interatrial Block Predicts Atrial Fibrillation and Total Mortality in Patients with Cardiac Resynchronization Therapy 2020 Ingår i: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; , s. 720-729 Tidskriftsartikel (refereegranskat)abstract Background: Interatrial block (IAB) and abnormal P-wave terminal force in lead V1 (PTFV1) are electrocardiographic (ECG) abnormalities that have been shown to be associated with new-onset atrial fibrillation (AF) and death. However, their prognostic importance has not been proven in cardiac resynchronization therapy (CRT) recipients. Objective: To assess if IAB and abnormal PTFV1 are associated with new-onset AF or death in CRT recipients. Methods: CRT recipients with sinus rhythm ECG at CRT implantation and no AF history were included (n = 210). Automated analysis of P-wave duration (PWD) and morphology classified patients as having either no IAB (PWD <120 ms), partial IAB (pIAB: PWD ≥120 ms, positive P waves in leads II and aVF), or advanced IAB (aIAB: PWD ≥120 ms and biphasic or negative P wave in leads II or aVF). PTFV1 >0.04 mm•s was considered abnormal. Adjusted Cox regression analyses were performed to assess the impact of IAB and abnormal PTFV1 on the primary endpoint new-onset AF, death, or heart transplant (HTx) and the secondary endpoint death or HTx at 5 years of follow-up. Results: IAB was found in 45% of all patients and independently predicted the primary endpoint with HR 1.9 (95% CI 1.2-2.9, p = 0.004) and the secondary endpoint with HR 2.1 (95% CI 1.2-3.4, p = 0.006). Abnormal PTFV1 was not associated with the endpoints. Conclusions: IAB is associated with new-onset AF and death in CRT recipients and may be helpful in the risk stratification in the context of heart failure management. Abnormal PTFV1 did not demonstrate any prognostic value.
44.	Johnson, Linda S, et al. (författare) Markers of Atrial Myopathy in the General Population Prevalence, Predictors, and Inter-Relations 2023 Ingår i: JACC. - : Elsevier. - 2405-500X .- 2405-5018. ; 9:11, s. 2240-2249 Tidskriftsartikel (refereegranskat)abstract 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 mss. 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 (rho = 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 (beta-coefficient = 3.1; P < 0.0001) and body mass index was associated with P-wave duration (beta-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.
45.	Karlsson, Mattias, et al. (författare) Drug Dependent Circadian Variations in AV-nodal Properties During Atrial Fibrillation 2022 Ingår i: 2022 Computing in Cardiology, CinC 2022. - 2325-887X .- 2325-8861. - 9798350300970 ; 2022-September Konferensbidrag (refereegranskat)abstract The heart rate during atrial fibrillation (AF) is highly dependent on the conduction properties of the atrioventricular (AV) node, which can be affected using β-blockers or calcium channel blockers, often chosen empirically. Thus, characterization of the AV nodal conduction properties could contribute to personalized treatment of AF. We have created a mathematical network model of the AV node where continuous estimation of the refractory period and conduction delay from 24-hour ambulatory ECGs from patients with permanent AF (n=59) was achieved using a problem-specific genetic algorithm. Circadian variations in the resulting model parameter trends were quantified using cosinor analysis, and differences between treatment with β-blockers and calcium blockers were assessed using a linear-mixed effect approach. The mixed-effects analysis indicated increased refractoriness relative to baseline for all drugs. For the β-blockers, an additional decrease in circadian variation for parameters representing conduction delay was observed. This indicates that the two drug types have quantifiable differences in their effects on AV-nodal conduction properties. The proposed method enables analysis of circadian variation in AV node conduction delay and refractoriness from 24h ambulatory ECG, which can be used to monitor and possibly predict the effect of rate control drugs.
46.	Karlsson, Mattias, et al. (författare) ECG-based Assessment and Therapeutic Implications of AV Nodal Conduction Dynamics During Atrial Fibrillation 2023 Ingår i: Computing in Cardiology, CinC 2023. - 2325-887X .- 2325-8861. - 9798350382525 ; 50 Konferensbidrag (refereegranskat)abstract The conduction properties of the atrioventricular (AV) node have a significant impact on heart rate during permanent atrial fibrillation (AF), and can be modulated through the use of β-blockers or calcium channel blockers. These drugs have different physiological effects and are often selected empirically. Hence, an improved understanding of how these drugs affect the AV node conduction properties may contribute to personalized treatment of AF. We propose a novel methodology for estimating the refractory period and conduction delay dynamics of the fast and slow pathways of the AV node from 24-hour ambulatory ECG recordings. Our approach comprises a network model of the AV node, a problem-specific genetic algorithm, and an approximate Bayesian computation algorithm for estimating the posterior distribution of the AV node properties. We analyzed 24-hour ambulatory ECG recordings at baseline from 51 patients with permanent AF. Interestingly, a moderate correlation between the short-term variability in the refractory period for the fast pathway and reduction in heart rate during treatment with metoprolol (ρ = 0.48, p < 0.005) was found. Thus, the proposed methodology enables individualized characterization of the AV node and can potentially assist in treatment selection.
47.	Karlsson, Mattias, et al. (författare) ECG based assessment of circadian variation in AV-nodal conduction during AF—Influence of rate control drugs 2022 Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 13 Tidskriftsartikel (refereegranskat)abstract 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.
48.	Karlsson, Mattias, et al. (författare) Model-based estimation of AV-nodal refractory period and conduction delay trends from ECG 2023 Ingår i: Frontiers in Physiology. - 1664-042X. ; 14 Tidskriftsartikel (refereegranskat)abstract 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.
49.	Lindow, Thomas, et al. (författare) Low diagnostic yield of ST elevation myocardial infarction amplitude criteria in chest pain patients at the emergency department 2021 Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; , s. 1-8 Tidskriftsartikel (refereegranskat)abstract To evaluate the diagnostic yield of the ECG criteria for ST-elevation myocardial infarction in a large cohort of emergency department chest pain patients, and to determine whether extended ECG criteria or reciprocal ST depression can improve accuracy. Design: Observational, register-based diagnostic study on the accuracy of ECG criteria for ST-elevation myocardial infarction. Between Jan 2010 and Dec 2014 all patients aged ≥30 years with chest pain who had an ECG recorded within 4 h at two emergency departments in Sweden were included. Exclusion criteria were: ECG with poor technical quality; QRS duration ≥120 ms; ECG signs of left ventricular hypertrophy; or previous coronary artery bypass surgery. Conventional and extended ECG criteria were applied to all patients. The main outcome was acute myocardial infarction (AMI) and an occluded/near-occluded coronary artery at angiography. Results: Finally, 19932 patients were included. Conventional ECG criteria for ST elevation myocardial infarction were fulfilled in 502 patients, and extended criteria in 1249 patients. Sensitivity for conventional ECG criteria in diagnosing AMI with coronary occlusion/near-occlusion was 17%, specificity 98% and positive predictive value 12%. Corresponding data for extended ECG criteria were 30%, 94% and 8%. When reciprocal ST depression was added to the criteria, the positive predictive value rose to 24% for the conventional and 23% for the extended criteria. Conclusions: In unselected chest pain patients at the emergency department, the diagnostic yield of both conventional and extended ECG criteria for ST-elevation myocardial infarction is low. The PPV can be increased by also considering reciprocal ST depression.
50.	Mannewald, Christine, et al. (författare) Prevalence of left atrial appendage thrombus and spontaneous echo contrast on transesophageal echocardiography in patients scheduled for pulmonary vein isolation 2024 Ingår i: Annals of Noninvasive Electrocardiology. - 1082-720X. ; 29:3 Tidskriftsartikel (refereegranskat)abstract 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 CHA2DS2-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 CHA2DS2-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 CHA2DS2-VASc 0, paroxysmal AF, normal sized left atrium and sinus rhythm at TEE were found to have LAAT or SEC.

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