Publications by authors named "Jonas Carlson"

62 Publications

Terminal T-wave inversion predicts reperfusion tachyarrhythmias in STEMI.

J Electrocardiol 2022 Jan 5;71:28-31. Epub 2022 Jan 5.

Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden; Arrhythmia Clinic, Skåne University Hospital, 22185 Lund, Sweden.

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, T-T, 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.
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http://dx.doi.org/10.1016/j.jelectrocard.2021.12.008DOI Listing
January 2022

Atrial fibrillatory rate as predictor of recurrence of atrial fibrillation in horses treated medically or with electrical cardioversion.

Equine Vet J 2021 Dec 27. Epub 2021 Dec 27.

Department of Cardiology, Lund University, Lund, Sweden.

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.
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http://dx.doi.org/10.1111/evj.13551DOI Listing
December 2021

Relation of Early Monomorphic Ventricular Tachycardia to Long-Term Mortality in ST-Elevation Myocardial Infarction.

Am J Cardiol 2022 Jan 10;163:13-19. Epub 2021 Nov 10.

Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.

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.
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http://dx.doi.org/10.1016/j.amjcard.2021.09.037DOI Listing
January 2022

Evolution of P-wave indices during long-term follow-up as markers of atrial substrate progression in arrhythmogenic right ventricular cardiomyopathy.

Europace 2021 03;23(23 Suppl 1):i29-i37

Department of Cardiology, Clinical Sciences, Lund University, SE-221 85 Lund, Sweden.

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.
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http://dx.doi.org/10.1093/europace/euaa388DOI Listing
March 2021

Interatrial Block Predicts Atrial Fibrillation and Total Mortality in Patients with Cardiac Resynchronization Therapy.

Cardiology 2020 6;145(11):720-729. Epub 2020 Oct 6.

Lund University, Department of Cardiology, Clinical Sciences, Skane University Hospital, Lund, Sweden.

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.
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http://dx.doi.org/10.1159/000509916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677995PMC
August 2021

Vectorcardiography Findings Are Associated with Recurrent Ventricular Arrhythmias and Mortality in Patients with Heart Failure Treated with Implantable Cardioverter-Defibrillator Device.

Cardiology 2020 21;145(12):784-794. Epub 2020 Sep 21.

Department of Cardiology, Clinical Sciences, Lund University, Arrhythmia Clinic, Skane University Hospital, Lund, Sweden.

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.
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http://dx.doi.org/10.1159/000509766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845434PMC
August 2021

Pregnancies, ventricular arrhythmias, and substrate progression in women with arrhythmogenic right ventricular cardiomyopathy in the Nordic ARVC Registry.

Europace 2020 12;22(12):1873-1879

Department of Cardiology, Centre of Cardiac-, Vascular-, Pulmonary- and Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.

Aims: Women with arrhythmogenic right ventricular cardiomyopathy (ARVC) are at relatively lower risk of ventricular arrhythmias (VAs) than men, but the physical burden associated with pregnancy on VA risk remains insufficiently studied. We aimed to assess the risk of VA in relation to pregnancies in women with ARVC.

Methods And Results: We included 199 females with definite ARVC (n = 121) and mutation-positive family members without ascertained ARVC diagnosis (n = 78), of whom 120 had at least one childbirth. Ventricular arrhythmia-free survival after the latest childbirth was compared between women with one (n = 20), two (n = 67), and three or more (n = 37) childbirths. Cumulative probability of VA for each pregnancy (n = 261) was assessed from conception through 2 years after childbirth and compared between those pregnancies that occurred before (n = 191) or after (n = 19) ARVC diagnosis and in mutation-positive family members (n = 51). The nulliparous women had lower median age at ARVC diagnosis (38 vs. 42 years, P < 0.001) and first VA (22 vs. 41 years, P < 0.001). Ventricular arrhythmia-free survival after the latest childbirth was not related to the number of pregnancies. No pregnancy-related VA was reported among the family members. Women who gave birth after ARVC diagnosis had elevated risk of VA postpartum (hazard ratio 13.74, 95% confidence interval 2.9-63, P = 0.001), though only two events occurred during pregnancies.

Conclusion: In women with ARVC, pregnancy was uneventful for the overwhelming majority and the number of prior completed pregnancies was not associated with VA risk. Pregnancy-related VA was primarily related to the phenotypical severity rather than pregnancy itself.
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http://dx.doi.org/10.1093/europace/euaa136DOI Listing
December 2020

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.

Europace 2020 08;22(8):1173-1181

Department of Cardiology, Center for Integrative Electrocardiography, Clinical Sciences at Lund University and Arrhythmia Clinic, Skåne University Hospital, Entrégatan 7, 22185 Lund, Sweden.

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.
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http://dx.doi.org/10.1093/europace/euaa118DOI Listing
August 2020

Early repolarization pattern on ECG recorded before the acute coronary event does not predict ventricular fibrillation during ST-elevation myocardial infarction.

Heart Rhythm 2020 04 15;17(4):629-636. Epub 2019 Nov 15.

Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.

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.
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http://dx.doi.org/10.1016/j.hrthm.2019.11.011DOI Listing
April 2020

Longitudinal study of electrical, functional and structural remodelling in an equine model of atrial fibrillation.

BMC Cardiovasc Disord 2019 10 21;19(1):228. Epub 2019 Oct 21.

Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Højbakkegaard Allé 5, 2630, Taastrup, Denmark.

Background: Large animal models are important in atrial fibrillation (AF) research, as they can be used to study the pathophysiology of AF and new therapeutic approaches. Unlike other animal models, horses spontaneously develop AF and could therefore serve as a bona fide model in AF research. We therefore aimed to study the electrical, functional and structural remodelling caused by chronic AF in a horse model.

Method: Nine female horses were included in the study, with six horses tachypaced into self-sustained AF and three that served as a time-matched sham-operated control group. Acceleration in atrial fibrillatory rate (AFR), changes in electrocardiographic and echocardiographic variables and response to medical treatment (flecainide 2 mg/kg) were recorded over a period of 2 months. At the end of the study, changes in ion channel expression and fibrosis were measured and compared between the two groups.

Results: AFR increased from 299 ± 33 fibrillations per minute (fpm) to 376 ± 12 fpm (p < 0.05) and atrial function (active left atrial fractional area change) decreased significantly during the study (p < 0.05). No changes were observed in heart rate or ventricular function. The AF group had more atrial fibrosis compared to the control group (p < 0.05). No differences in ion channel expression were observed.

Conclusion: Horses with induced AF show signs of atrial remodelling that are similar to humans and other animal models.
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http://dx.doi.org/10.1186/s12872-019-1210-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805623PMC
October 2019

Atrial fibrillation incidence and impact of biventricular pacing on long-term outcome in patients with heart failure treated with cardiac resynchronization therapy.

BMC Cardiovasc Disord 2019 08 13;19(1):195. Epub 2019 Aug 13.

Department of Cardiology, Clinical Sciences, Lund University, 221 85, Lund, Sweden.

Background: In patients with cardiac resynchronization therapy (CRT), atrial fibrillation (AF) is associated with an unfavorable outcome and may cause loss of biventricular pacing (BivP). An effective delivery of BivP of more than 98% of all ventricular beats has been shown to be a major determinant of CRT-success.

Methods: At a Swedish tertiary referral center, data was retrospectively obtained from patient registers, medical records and preoperative electrocardiograms. Data regarding AF and BivP during the first year of follow-up was assessed from CRT-device interrogations. No intra-cardiac electrograms were studied. Kaplan-Meier curves and Cox-regression analyses adjusted for age, etiology of heart failure, left ventricular ejection fraction, left bundle branch block and NYHA class were performed to assess the impact of AF and BivP on the risk of death or heart transplantation (HTx) at 10-years of follow-up.

Results: Preoperative AF-history was found in 54% of the 379 included patients and was associated with, but did not independently predict death or HTx. The one-year incidence of new device-detected AF was 22% but not associated with poorer prognosis. At one-year, AF-history and BivP≤98%, was associated with a higher risk of death or HTx compared to patients without AF (HR 1.9, 95%CI 1.2-3.0, p = 0.005) whereas AF and BivP> 98% was not (HR 1.4, 95%CI 0.9-2.3, p = 0.14).

Conclusions: In CRT-recipients, AF-history is common and associated with poor outcome. AF-history does not independently predict mortality and is probably only a marker of a more severe underlying disease. BivP≤98% during first-year of CRT-treatment independently predicts poor outcome thus further supporting the use of 98% threshold of BivP, which should be attained to maximize the benefits of CRT.
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http://dx.doi.org/10.1186/s12872-019-1169-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693170PMC
August 2019

Atrial fibrillation as a clinical characteristic of arrhythmogenic right ventricular cardiomyopathy: Experience from the Nordic ARVC Registry.

Int J Cardiol 2020 01 30;298:39-43. Epub 2019 Jul 30.

Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.

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.
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http://dx.doi.org/10.1016/j.ijcard.2019.07.086DOI Listing
January 2020

Genetic variants on chromosomes 7p31 and 12p12 are associated with abnormal atrial electrical activation in patients with early-onset lone atrial fibrillation.

Ann Noninvasive Electrocardiol 2019 11 1;24(6):e12661. Epub 2019 Jun 1.

The Center for Integrative Electrocardiology, Arrhythmia Clinic Skåne University Hospital, Lund University (CIEL), Lund, Sweden.

Background: Abnormal P-wave morphology (PWM) has been associated with a history of atrial fibrillation (AF) in earlier studies. Although lone AF is believed to have substantial genetic basis, studies on associations between single nucleotide polymorphisms (SNP) linked to lone AF and PWM have not been reported. We aimed to assess whether SNPs previously associated with lone AF (rs2200733, rs13376333, rs3807989, and rs11047543) are also linked to P-wave abnormalities.

Methods: Four SNPs were studied in 176 unrelated individuals with early-onset lone AF (age at onset <50 years), median age 38 years (19-63 years), 149 men. Using sinus rhythm ECG, orthogonal PWM was classified as Type 1-positive in leads X and Y and negative in lead Z, Type 2-positive in leads X and Y and biphasic (-/+) in lead Z, Type 3-positive in lead X and biphasic in lead Y (+/-), and the remaining as atypical.

Results: Two SNPs were found to be significantly associated with altered P-wave morphology distribution: rs3807989 near the gene CAV1/CAV2 and rs11047543 near the gene SOX5. Both SNPs were associated with a higher risk of non-Type 1 P-wave morphology (rs3807989: OR = 4.8, 95% CI = 2.3-10.2, p < 0.001; rs11047543: OR = 4.7, 95% CI = 1.1-20.5, p = 0.04). No association was observed for rs2200733 and rs13376333.

Conclusion: In this study, the two variants rs3807989 and rs11047543, previously associated with PR interval and lone AF, were associated with altered P-wave morphology distribution in patients with early-onset lone AF. These findings suggest that common genetic variants may modify atrial conduction properties.
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http://dx.doi.org/10.1111/anec.12661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931409PMC
November 2019

Primary Prevention of Sudden Cardiac Death With Implantable Cardioverter-Defibrillator Therapy in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

Am J Cardiol 2019 04 8;123(7):1156-1162. Epub 2019 Jan 8.

Department of Cardiology, The Heart Center, Rigshospitalet, University of Copenhagen, Denmark & Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Implantable cardioverter-defibrillator (ICD) therapy remains a corner stone of sudden cardiac death (SCD) prevention in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed to assess predictors of appropriate ICD therapies in the Scandinavian cohort of ARVC patients who received ICD for primary prevention of SCD. Study group comprised of 79 definite ARVC patients by 2010 Task Force criteria (60% male, age at ICD implant 39 ± 14 years) who were enrolled in the Nordic ARVC Registry and received an ICD for primary SCD prevention. The primary end point of appropriate ICD shock or death from any cause was assessed and compared with 137 definite ARVC patients who received ICD for secondary SCD prevention (74% male, age at ICD implant 42 ± 15 years). In the study group, 38% were ≤35 years of age at baseline, 25% had nonsustained ventricular tachycardia, and 29% had syncope at baseline. Major repolarization abnormality (hazard ratio = 4.00, 95% confidence interval 1.30 to 12.30, p = 0.015) and age ≤35 years (hazard ratio = 4.21, 95% confidence interval 1.49 to 11.85, p = 0.001) independently predicted the primary end point. The outcome did not differ between the primary prevention patients with either of these risk factors and the secondary prevention cohort (2% to 4% annual event rate) whereas patients without risk factors did not have any appropriate ICD shocks during follow-up. In conclusion, young age at ARVC diagnosis and major repolarization abnormality independently predict ICD shocks or death in the primary prevention ICD recipients and associated with the event rate similar to the one observed in the secondary prevention cohort. Our data indicate the benefit of ICD for primary prevention in patients with any of these risk factors.
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http://dx.doi.org/10.1016/j.amjcard.2018.12.049DOI Listing
April 2019

Effects of dofetilide and ranolazine on atrial fibrillatory rate in a horse model of acutely induced atrial fibrillation.

J Cardiovasc Electrophysiol 2019 04 28;30(4):596-606. Epub 2019 Jan 28.

Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.

Introduction: The atrial fibrillatory rate is a potential biomarker in the study of antiarrhythmic drug effects on atrial fibrillation (AF). The purpose of this study was to evaluate whether dose-dependent changes in the atrial fibrillatory rate can be monitored on surface electrocardiography (ECG) following treatment with dofetilide, ranolazine, and a combination of the two in an acute model of AF in horses.

Methods And Results: Eight horses were subjected to pacing-induced AF on 4 separate days. Saline (control), dofetilide, ranolazine, or a combination of dofetilide and ranolazine was administered in four incremental doses. Atrial fibrillatory activity was extracted from surface ECGs using spatiotemporal QRST cancellation. The mean atrial fibrillatory rate before drug infusion was 297 ± 27 fpm. Dofetilide reduced the atrial fibrillatory rate following the infusion of low doses (0.89 µg/kg, P < 0.05) and within 5 minutes preceding cardioversion (P < 0.05). Cardioversion with ranolazine was preceded by a reduction in the atrial fibrillatory rate in the last minute (P < 0.05). The combination of drugs reduced the atrial fibrillatory rate in a similar manner to dofetilide used alone. A trend toward a lower atrial fibrillatory rate before drug infusion was found among horses cardioverting on low doses of the drugs.

Conclusion: The atrial fibrillatory rate derived from surface ECGs showed a difference in the mode of action on AF between dofetilide and ranolazine. Dofetilide reduced the atrial fibrillatory rate, whereas ranolazine displayed a cardioverting mechanism that was distinct from a slowing of the fibrillatory process.
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http://dx.doi.org/10.1111/jce.13849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849868PMC
April 2019

The S-wave angle identifies arrhythmogenic right ventricular cardiomyopathy in patients with electrocardiographically concealed disease phenotype.

J Electrocardiol 2018 Nov - Dec;51(6):1003-1008. Epub 2018 Aug 10.

Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden; Cardiovascular Department, Ospedali Riuniti and University of Trieste, Trieste, Italy; Arrhythmia Clinic, Skåne University Hospital, Lund, Sweden.

Background: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) carries risk of sudden death. We hypothesize that the S-wave angle differentiates ARVD/C with otherwise normal electrocardiograms from controls.

Materials And Methods: All patients met Task Force 2010 definite ARVD/C criteria. ARVD/C patients without Task Force depolarization/repolarization criteria (-ECG) were compared to controls. Electrocardiogram measures of QRS duration, corrected QT interval, and measured angle between the upslope and downslope of the S-wave in V2, were assessed.

Results: Definite ARVD/C was present in 155 patients (42.7 ± 17.3 years, 68.4%male). -ECG ARVD/C patients (66 patients) were compared to 66 control patients (41.8 ± 17.6 years, 65.2%male). Only the S-wave angle differentiated -ECG ARVD/C patients from controls (<0.001) with AU the ROC curve of 0.77 (95%CI 0.53 to 0.71) and odds ratio of 28.3 (95%CI 6.4 to 125.5).

Conclusion: ARVD/C may lead to development of subtle ECG abnormalities distinguishable using the S-wave angle prior to development of 2010 Taskforce ECG criteria.
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http://dx.doi.org/10.1016/j.jelectrocard.2018.08.009DOI Listing
October 2019

A decade of catheter ablation of cardiac arrhythmias in Sweden: ablation practices and outcomes.

Eur Heart J 2019 03;40(10):820-830

Department of Cardiology, Karolinska University Hospital, SE-171 76, Solna, Sweden.

Aims: Catheter ablation is considered the treatment of choice for many tachyarrhythmias, but convincing 'real-world' data on efficacy and safety are lacking. Using Swedish national registry data, the ablation spectrum, procedural characteristics, as well as ablation efficacy and reported adverse events are reported.

Methods And Results: Consecutive patients (≥18 years of age) undergoing catheter ablation in Sweden between 01 January 2006 and 31 December 2015 were included in the study. Follow-up (repeat ablation and vital status) was collected through 31 December 2016. A total of 26 642 patients (57 ± 15 years, 62% men), undergoing a total of 34 428 ablation procedures were included in the study. In total, 4034 accessory pathway/Wolff-Parkinson-White syndrome (12%), 7358 AV-nodal re-entrant tachycardia (21%), 1813 atrial tachycardia (5.2%), 5481 typical atrial flutter (16%), 11 916 atrial fibrillation (AF, 35%), 2415 AV-nodal (7.0%), 581 premature ventricular contraction (PVC, 1.7%), and 964 ventricular tachycardia (VT) ablations (2.8%) were performed. Median follow-up time was 4.7 years (interquartile range 2.7-7.0). The spectrum of treated arrhythmias changed over time, with a gradual increase in AF, VT, and PVC ablation (P < 0.001). Decreasing procedural times and utilization of fluoroscopy with time, were seen for all arrhythmia types. The rates of repeat ablation differed between ablation types, with the highest repeat ablation seen in AF (41% within 3 years). The rate of reported adverse events was low (n = 595, 1.7%). Death in the immediate period following ablation was rare (n = 116, 0.34%).

Conclusion: Catheter ablations have shifted towards more complex procedures over the past decade. Fluoroscopy time has markedly decreased and the efficacy of catheter ablation seems to improve for AF.
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http://dx.doi.org/10.1093/eurheartj/ehy709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403459PMC
March 2019

Usefulness of Electrocardiographic Left Atrial Abnormality to Predict Response to Cardiac Resynchronization Therapy in Patients With Mild Heart Failure and Left Bundle Branch Block (a Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy Substudy).

Am J Cardiol 2018 07 11;122(2):268-274. Epub 2018 Apr 11.

Department of Cardiology, Clinical Sciences, Lund University, Lund Sweden; Cardiology Division, Heart Research Follow-up Program, University of Rochester Medical Center, Rochester, New York.

Cardiac resynchronization therapy (CRT) has proven prognostic benefits in patients with heart failure (HF) with left bundle branch block (LBBB) QRS morphology. Electrocardiographic left atrial (LA) abnormality has been proposed as a noninvasive marker of atrial remodeling. We aimed to assess the impact of electrocardiographic LA abnormality for prognosis in patients with HF treated with CRT. Baseline resting 12-lead electrocardiograms recorded from 941 patients enrolled in the CRT arm of the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy was processed automatically using Glasgow algorithm, which included automated assessment of P-wave terminal force in lead V (PTF-V) as a marker of LA abnormality. A PTF-V of ≥0.04 mm⋅s was considered abnormal. The primary end point was HF event and/or death. Total mortality and appropriate defibrillator therapies were the secondary end points. At baseline 550, patients treated with CRT with a defibrillator had LBBB QRS morphology and normal PTF-V. Normal PTF-V was associated with significant risk reduction for all assessed end points and for the primary end point comprised a hazard ratio of 0.55 (95% confidence interval 0.36 to 0.84) compared with patients with LBBB with abnormal PTF-V (n = 120), and a hazard ratio of 0.42 (95% confidence interval 0.32 to 0.55) compared with patients with implanted defibrillator (n = 729). In CRT-treated patients with HF, electrocardiographic LA abnormality appears to be an electrocardiographic indicator of poor long-term outcome in patients with LBBB. In conclusion, our data suggest that PTF-V bears additive prognostic information in the context of CRT, thus further strengthening the role of electrocardiographic diagnostics in risk stratification of patients with HF.
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http://dx.doi.org/10.1016/j.amjcard.2018.03.364DOI Listing
July 2018

Effect of flecainide on atrial fibrillatory rate in a large animal model with induced atrial fibrillation.

BMC Cardiovasc Disord 2017 Dec 8;17(1):289. Epub 2017 Dec 8.

Arrhythmia Clinic, Skåne University Hospital and Department of Cardiology, Clinical Sciences, Lund University, 21185, Lund, Sweden.

Background: Atrial fibrillatory cycle length has been considered one of the indices of atrial electrical remodelling during atrial fibrillation (AF), which can be assessed from surface ECG by computer-assisted calculation of atrial fibrillatory rate (AFR). Horses have been suggested as a bona fide model for AF studies since horses too, develop lone AF, however data on AF characteristics in horses are extremely sparse and non-invasive characterization of AF complexity using surface ECG processing has not been reported.

Aim: The aim was to study characteristics of induced AF and its modification by flecainide.

Methods: The study group consisted on 3 horses with spontaneous persistent AF and 13 with pace-induced AF. Seven horses were treated with saline (control) and eight with flecainide (2 mg/kg). ECGs were analysed using spatiotemporal cancellation of QRST complexes and calculation of AFR from the residual atrial signal.

Results: At AF onset, AFR was 295 ± 52 fibrillations per minute (fpm) in the horses with induced AF treated with flecainide, 269 ± 36 fpm in the control group (ns), and 364 ± 26 fpm in the horses with spontaneous persistent AF (P < 0.05 compared to the control group). Flecainide caused a decrease in AFR in all animals and restored sinus rhythm in the animals with induced AF. In the control animals, AFR increased from 269 ± 36 fpm to a plateau of 313 ± 14 fpm before decreasing to 288 ± 28 fpm during the last 10% of the AF episodes preceding spontaneous conversion (P < 0.05).

Conclusion: AFR in horses with induced AF resembles AFR in humans with paroxysmal AF. Flecainide caused a rapid decrease in AFR in all horses, further supporting the method to be a non-invasive technique to study the effect of antiarrhythmic compounds.
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http://dx.doi.org/10.1186/s12872-017-0720-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723027PMC
December 2017

Orthogonal P-wave morphology is affected by intra-atrial pressures.

BMC Cardiovasc Disord 2017 Dec 6;17(1):288. Epub 2017 Dec 6.

Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.

Background: It has previously been shown that the morphology of the P-wave neither depends on atrial size in healthy subjects with physiologically enlarged atria nor on the physiological anatomical variation in transverse orientation of the left atrium. The present study aimed to investigate if different pressures in the left and right atrium are associated with different P-wave morphologies.

Methods: 38 patients with isolated, increased left atrial pressure, 51 patients with isolated, increased right atrial pressure and 76 patients with biatrially increased pressure were studied. All had undergone right heart catheterization and had 12-lead electrocardiographic recordings, which were transformed into vectorcardiograms for detailed P-wave morphology analysis.

Results: Normal P-wave morphology (type 1) was more common in patients with isolated increased pressure in the right atrium while abnormal P-wave morphology (type 2) was more common in the groups with increased left atrial pressure (P = 0.032). Moreover, patients with increased left atrial pressure, either isolated or in conjunction with increased right atrial pressure, had significantly more often a P-wave morphology with a positive deflection in the sagittal plane (P = 0.004).

Conclusion: Isolated elevated right atrial pressure was associated with normal P-wave morphology while left-sided atrial pressure elevation, either isolated or in combination with right atrial pressure elevation, was associated with abnormal P-wave morphology.
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http://dx.doi.org/10.1186/s12872-017-0724-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719760PMC
December 2017

Right precordial-directed electrocardiographical markers identify arrhythmogenic right ventricular cardiomyopathy in the absence of conventional depolarization or repolarization abnormalities.

BMC Cardiovasc Disord 2017 Oct 13;17(1):261. Epub 2017 Oct 13.

Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.

Background: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) carries a risk of sudden death. We aimed to assess whether vectorcardiographic (VCG) parameters directed toward the right heart and a measured angle of the S-wave would help differentiate ARVD/C with otherwise normal electrocardiograms from controls.

Methods: Task Force 2010 definite ARVD/C criteria were met for all patients. Those who did not fulfill Task Force depolarization or repolarization criteria (-ECG) were compared with age and gender-matched control subjects. Electrocardiogram measures of a 3-dimentional spatial QRS-T angle, a right-precordial-directed orthogonal QRS-T (RPD) angle, a root mean square of the right sided depolarizing forces (RtRMS-QRS), QRS duration (QRSd) and the corrected QT interval (QTc), and a measured angle including the upslope and downslope of the S-wave (S-wave angle) were assessed.

Results: Definite ARVD/C was present in 155 patients by 2010 Task Force criteria (41.7 ± 17.6 years, 65.2% male). -ECG ARVD/C patients (66 patients) were compared to 66 control patients (41.7 ± 17.6 years, 65.2% male). All parameters tested except the QRSd and QTc significantly differentiated -ECG ARVD/C from control patients (p < 0.004 to p < 0.001). The RPD angle and RtRMS-QRS best differentiated the groups. Combined, the 2 novel criteria gave 81.8% sensitivity, 90.9% specificity and odds ratio of 45.0 (95% confidence interval 15.8 to 128.2).

Conclusion: ARVD/C disease process may lead to development of subtle ECG abnormalities that can be distinguishable using right-sided VCG or measured angle markers better than the spatial QRS-T angle, the QRSd or QTc, in the absence of Taskforce ECG criteria.
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http://dx.doi.org/10.1186/s12872-017-0696-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640940PMC
October 2017

Atrial time and voltage dispersion are both needed to predict new-onset atrial fibrillation in ischemic stroke patients.

BMC Cardiovasc Disord 2017 07 24;17(1):200. Epub 2017 Jul 24.

Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.

Background: Atrial fibrillation (AF) is a known risk factor for ischemic stroke. Electrocardiographic predictors of AF in population studies such as the Framingham Heart Study, as well as in hypertensive patients have demonstrated a predictive value of the P-wave duration for development of AF. QRS vector magnitude has had a predictive value in ventricular arrhythmia development. We aimed to assess the value of the three-dimensional P-wave vector magnitude and its relationship to P-wave duration for prediction of new-onset AF after ischemic stroke.

Methods: First-ever ischemic stroke patients without AF at inclusion in the Lund Stroke Register were included. Measurements of P wave duration (Pd), QRS duration, corrected QT interval, and PQ interval were performed automatically using the University of Glasgow 12-lead ECG analysis algorithm. The P-wave vector magnitude (Pvm) was calculated automatically as the square root of the sum of the squared P-wave magnitudes in leads V6, II and one half of the P-wave amplitude in V2 ([Formula: see text]), based on the P-wave magnitude (Pvm) as defined by the visually transformed Kors' Quasi-orthogonal method.

Results: The median age was 73 (IQR 63-80) years at stroke onset (135 males, 92 females). Multivariate predictors of new-onset atrial fibrillation included age > 65 years, hypertension, and Pd/Pvm. A cut-off value of 870 ms/mV gave sensitivity, specificity, positive and negative predictive values of 51, 79, 30 and 87%, respectively. The Pd/Pvm was the only ECG predictor of AF with a significant multivariate hazard ratio of 2.02 (95% CI 1.18 to 3.46, p = 0.010).

Conclusion: P-wave dispersion as measured by the Pd/Pvm was the only ECG parameter measured which independently predicted subsequent AF identification in a cohort of stroke patients. Further prospective studies in larger cohorts are needed to validate its clinical usefulness.
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http://dx.doi.org/10.1186/s12872-017-0631-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525302PMC
July 2017

Non-permanent atrial fibrillation and oral anticoagulant therapy are related to survival during 10years after first-ever ischemic stroke.

Int J Cardiol 2017 Apr 5;232:134-139. Epub 2017 Jan 5.

Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden; Arrythmia Clinic, Skåne University Hospital, Lund, Sweden.

Background: Atrial fibrillation (AF) detection in ischemic stroke patients triggers initiation of oral anticoagulant therapy (OAC). However, little is known regarding whether the persistency of AF affects long-term prognosis after ischemic stroke. We aimed to assess the impact of AF types and OAC on the outcome during a 10-year follow-up (FU) after first-ever ischemic stroke.

Material And Methods: The study sample comprised 336 first-ever ischemic stroke patients (median age 76, interquartile range 25-75% (IQR) 67-82years, 136 female) included in the Lund Stroke Register (LSR) in 2001-2002. At baseline, 109 patients had either permanent (n=44) or recurrent (n=65) AF. OAC was assessed using the Lund University Hospital anticoagulation database. All-cause mortality was assessed via linkage with the Swedish Causes of Death Register.

Results: During FU, 200 patients died. AF independently predicted all-cause mortality (hazard ratio (HR) 1.52 95% CI 1.14-2.04, p=0.005); the worst prognosis was observed for permanent AF (HR 1.86 95% CI 1.29-2.69, p=0.001). Patients with recurrent AF receiving OAC had similar survival rates to patients without AF (HR 0.73 95% CI 0.38-1.39, p=0.333), while prognosis was worst for patients with permanent AF without OAC (HR 2.28 95% CI 1.38-3.77, p=0.001) and intermediate for patients with permanent AF on OAC (HR 1.57 95% CI 0.92-2.67, p=0.099).

Conclusion: All-cause mortality was independently associated with AF and was the greatest in stroke patients with permanent AF. Patients with recurrent AF receiving OAC have the most favorable outcome, similar to those without AF and significantly better than OAC-treated patients with permanent AF.
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http://dx.doi.org/10.1016/j.ijcard.2017.01.040DOI Listing
April 2017

Electrocardiographic and Echocardiographic predictors of paroxysmal atrial fibrillation detected after ischemic stroke.

BMC Cardiovasc Disord 2016 11 3;16(1):209. Epub 2016 Nov 3.

Department of Cardiology, Clinical Science, Lund University, Lund, SE-221 85, Sweden.

Background: Detection of atrial fibrillation after ischemic stroke is challenging due to its paroxysmal nature. We aimed to assess predictors of paroxysmal atrial fibrillation using non-invasive surface ECG and transthoracic echocardiography to select candidates for atrial fibrillation screening.

Methods: Ischemic stroke patients without documented atrial fibrillation (n = 110, 67 ± 10 years, 40 female) and a control group of age- and gender-matched patients with history of paroxysmal atrial fibrillation prior to stroke (n = 55, 67 ± 10 years, 19 female) comprised the study sample. Using non-invasive ECG monitoring for three weeks, short episodes of paroxysmal atrial fibrillation were detected in 24 of 110 patients (22 %). The standard 12-lead ECG with sinus rhythm at stroke onset was digitally processed and analyzed. Transthoracic echocardiography data were reviewed for these patients.

Results: Atrial fibrillation history was independently associated with P terminal force in lead V 1 > 40 mm*ms (OR 4.04 95 % CI 1.34-12.14, p = 0.013) and left atrial volume index (OR 1.08 95 % CI 1.03-1.13, p = 0.002; for LAVI > 40 mL/m OR 6.40 95 % CL 1.47-27.91, p = 0.013). Among patients without atrial fibrillation history, no ECG characteristics were predictive of atrial fibrillation detected after stroke. Left atrial volume index remained an independent predictor of atrial fibrillation detected after stroke (OR 1.09 95 % CI 1.02-1.16, p = 0.017). A cutoff of <40 mL/m had an 84 % negative predictive value for ruling out atrial fibrillation on ambulatory monitoring with a sensitivity of 50 % and a specificity of 86 %.

Conclusion: In a post hoc analysis, left atrial dilatation assessed by left atrial volume index independently predicted atrial fibrillation after stroke in patients without prior atrial fibrillation history, while the other clinical or ECG markers were not predictive of atrial fibrillation detected early after ischemic stroke.

Trial Registration: This study is a post hoc analysis from the prospective case-control study registered in December 2011, ClinicalTrials.gov ID: NCT01325545 .
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http://dx.doi.org/10.1186/s12872-016-0384-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093933PMC
November 2016

Physiological variation in left atrial transverse orientation does not influence orthogonal P-wave morphology.

Ann Noninvasive Electrocardiol 2017 Mar 17;22(2). Epub 2016 Aug 17.

Department of Cardiology, Lund University and Center for Integrative Electrocardiology at Lund University, Lund, Sweden.

Background: It has previously been demonstrated that orthogonal P-wave morphology in healthy athletes does not depend on atrial size, but the possible impact of left atrial orientation on P-wave morphology remains unknown. In this study, we investigated if left atrial transverse orientation affects P-wave morphology in different populations.

Methods: Forty-seven patients with atrial fibrillation, 21 patients with arrhythmogenic right ventricular cardiomyopathy, 67 healthy athletes, and 56 healthy volunteers were included. All underwent cardiac magnetic resonance imaging or computed tomography and the orientation of the left atrium was determined. All had 12-lead electrocardiographic recordings, which were transformed into orthogonal leads and orthogonal P-wave morphology was obtained.

Results: The median left atrial transverse orientation was 87 (83, 91) degrees (lower and upper quartiles) in the total study population. There was no difference in left atrial transverse orientation between individuals with different orthogonal P-wave morphologies.

Conclusions: The physiological variation in left atrial orientation was small within as well as between the different populations. There was no difference in left atrial transverse orientation between subjects with type 1 and type 2 P-wave morphology, implying that in this setting the P-wave morphology was more dependent on atrial conduction than orientation.
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http://dx.doi.org/10.1111/anec.12392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931582PMC
March 2017

Usefulness of the Sum Absolute QRST Integral to Predict Outcomes in Patients Receiving Cardiac Resynchronization Therapy.

Am J Cardiol 2016 08 14;118(3):389-95. Epub 2016 May 14.

Electrophysiology Chapter, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon. Electronic address:

Cardiac resynchronization therapy (CRT) reduces mortality and morbidity in selected patients with heart failure (HF), but up to 1/3 of patients are nonresponders. Sum absolute QRST integral (SAI QRST) recently showed association with mechanical response on CRT. However, it is unknown whether SAI QRST is associated with all-cause mortality and HF hospitalizations in patients undergoing CRT. The study population included 496 patients undergoing CRT (mean age 69 ± 10 years, 84% men, 65% left bundle branch block [LBBB], left ventricular ejection fraction 23 ± 6%, 63% ischemic cardiomyopathy). Preimplant digital 12-lead electrocardiogram was transformed into orthogonal XYZ electrocardiogram. SAI QRST was measured as an arithmetic sum of areas under the QRST curve on XYZ leads and was dichotomized based on the median value (302 mV ms). All-cause mortality served as the primary end point. A composite of 2-year all-cause mortality, heart transplant, and HF hospitalization was a secondary end point. Cox regression models were adjusted for known predictors of CRT response. Patients with preimplant low mean SAI QRST had an increased risk of both the primary (hazard ratio [HR] 1.8, 95% CI 1.01 to 3.2) and secondary (HR 1.6, 95% CI 1.1 to 2.2) end points after multivariate adjustment. SAI QRST was associated with secondary outcome in subgroups of patients with LBBB (HR 2.1, 95% CI 1.5 to 3.0) and with non-LBBB (HR 1.7, 95% CI 1.0 to 2.6). In patients undergoing CRT, preimplant SAI QRST <302 mV ms was associated with an increased risk of all-cause mortality and HF hospitalization. After validation in another prospective cohort, SAI QRST may help to refine selection of CRT recipients.
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http://dx.doi.org/10.1016/j.amjcard.2016.05.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4958489PMC
August 2016

Atrial average conduction velocity in patients with and without paroxysmal atrial fibrillation.

Clin Physiol Funct Imaging 2017 Nov 13;37(6):596-601. Epub 2016 Jan 13.

Section of Arrhythmias, Skåne University Hospital, Lund University, Lund, Sweden.

Objectives: To evaluate intra-atrial conduction delay in patients with atrial fibrillation (AF) via calculation of conduction velocities (CVs) of the right and left atria.

Methods: Electroanatomic mapping was performed during sinus rhythm, in the right atrium (RA) in eight patients with paroxysmal AF, in 12 controls with atrioventricular nodal re-entrant tachycardia (AVNRT) and in the left atrium (LA) in additional 16 AF patients. Three-dimensional maps of activation sequences of the RA and LA were obtained. Local CVs were specifically calculated in the direction of wave-front propagation on the activation maps by using 3-dimensional coordinates and local activation times of triads of sites. Average CVs of each atrium and each of 8 predefined RA and LA regions were calculated.

Results: During sinus rhythm, the average CVs of the RA were significantly slower (P<0·05) in the AF group (0·60 ± 0·12 m s ) than in the controls (0·83 ± 0·13 m s ). The average CVs of the RA basal, septal and annulus regions were significantly slower than the corresponding regions in controls (P<0·05). In patients with AF, the average CV of the LA was 0·51 ± 0·11 m s , which is significantly slower than that of the RA and than that of LA as previously reported (P<0·05).

Conclusion: Compared to patients with AVNRT, patients with AF are associated with conduction delay in both atria with the delay being more marked in the LA than in the RA, which suggests the involvement of conduction disturbances in the genesis and/or perpetuation of AF.
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http://dx.doi.org/10.1111/cpf.12342DOI Listing
November 2017

Predictors of new onset atrial fibrillation during 10-year follow-up after first-ever ischemic stroke.

Int J Cardiol 2015 Nov 14;199:248-52. Epub 2015 Jul 14.

Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden; Arrythmia Clinic, Skåne University Hospital, Lund, Sweden.

Background: Paroxysmal atrial fibrillation (AF) may be underdiagnosed in ischemic stroke patients but may be pivotal for initiation of oral anticoagulation therapy. We assessed clinical and ECG predictors of new-onset AF during 10-year follow-up (FU) in ischemic stroke patients.

Methods: The study sample comprised of 227 first-ever ischemic stroke patients without AF (median age 73, interquartile range 25%-75% 63-80years, 92 female) and 1:1 age- and gender-matched controls without stroke and AF enrolled in the Lund Stroke Register from March 2001 to February 2002. New-onset AF during FU was assessed by screening through regional ECG database and by record linkage with Swedish National Patient Register. The standard 12-lead sinus rhythm ECGs at stroke admission were retrieved from electronic database and digitally processed. Clinical baseline characteristics were studied using medical records.

Results: During FU, AF was found in 39 stroke patients and 30 controls, p=0.296. In stroke patients in multivariate Cox regression analysis AF was associated with hypertension (HR 3.45 CI 95% 1.40-3.49, p=0.007) and QRS duration (HR 1.02 CI 95% 1.00-1.03, p=0.049). High cardiovascular risk was predictive for AF development: for CHADS2≥4 HR 2.46 CI 95% 1.45-4.18, p=0.001 and for CHA2DS2-VASc≥5 HR 2.29 CI 95% 1.43-3.68, p=0.001. New onset AF was not associated with baseline ischemic stroke: HR 1.46 95% CI 0.90-2.35, p=0.121.

Conclusion: High CHADS2 and CHA2DS2-VASc scores, but not baseline ischemic stroke, predict new onset AF in FU. QRS duration might be considered a potential risk marker for prediction of AF after ischemic stroke.
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http://dx.doi.org/10.1016/j.ijcard.2015.07.047DOI Listing
November 2015

Peripheral microvascular function is altered in young individuals at risk for hypertrophic cardiomyopathy and correlates with myocardial diastolic function.

Am J Physiol Heart Circ Physiol 2015 Jun 20;308(11):H1351-8. Epub 2015 Mar 20.

Department of Pediatric Cardiology, Pediatric Heart Center, Skane University Hospital and Clinical Sciences, Lund University, Lund, Sweden;

Hypertrophic cardiomyopathy (HCM) is a major cause of sudden cardiac death in the young. Based on previous reports of functional abnormalities in not only coronary but also peripheral vessels in adults with HCM, we aimed to assess both peripheral vascular and myocardial diastolic function in young individuals with an early stage of HCM and in individuals at risk for HCM. Children, adolescents, and young adults (mean age: 12 yr) with a family history of HCM who either had (HCM group; n = 36) or did not have (HCM-risk group; n = 30) echocardiography-documented left ventricular (LV) hypertrophy as well as healthy matched controls (n = 85) and healthy young athletes (n = 12) were included in the study. All underwent assessment with 12-lead electrocardiography, two-dimensional echocardiography, tissue Doppler imaging and laser Doppler with transdermal iontophoresis of ACh and sodium nitroprusside. LV thickness and mass were increased in HCM and athlete groups compared with control and HCM-risk groups. The mitral E-to-e' ratio, measured via tissue Doppler, was increased in HCM (P < 0.0001) and HCM-risk (P < 0.01) groups compared with control and athlete groups, as were microvascular responses to ACh (HCM group: P = 0.045 and HCM-risk group: P = 0.02). Responses to ACh correlated with the E-to-e' ratio (r = 0.5, P = 0.001). Microvascular responses to sodium nitroprusside were similar in all groups (P > 0.2). HCM-causing mutations or its familial history are associated with changes in cardiac diastolic function and peripheral microvascular function even before the onset of myocardial hypertrophy. Tissue Doppler can be used to differentiate HCM from physiological LV hypertrophy in young athletes.
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http://dx.doi.org/10.1152/ajpheart.00714.2014DOI Listing
June 2015

Variability of P-wave morphology predicts the outcome of circumferential pulmonary vein isolation in patients with recurrent atrial fibrillation.

J Electrocardiol 2015 Mar-Apr;48(2):218-25. Epub 2014 Nov 28.

Department of Cardiology and Center for Integrative Electrocardiology at Lund University (CIEL), Lund University, Lund, Sweden.

Introduction: Severe atrial structural remodeling may reflect irreversible damage of the atrial tissue in patients with atrial fibrillation (AF) and is associated with changes of P-wave duration and morphology. Our aim was to study whether variability of P-wave morphology (PMV) is associated with outcome in patients with AF after circumferential PV isolation (CPVI).

Methods And Results: 70 consecutive patients (aged 60±9years, 46 men) undergoing CPVI due to symptomatic AF were studied. After cessation of antiarrhythmic therapy, standard 12-lead ECG during sinus rhythm was recorded for 10min at baseline and transformed to orthogonal leads. Beat-to-beat P-wave morphology was subsequently defined using a pre-defined classification algorithm. The most commonly observed P-wave morphology in a patient was defined as the dominant morphology. PMV was defined as the percentage of P waves with non-dominant morphology in the 10-min sample. At the end of follow-up, 53 of 70 patients had no arrhythmia recurrence. PMV was greater in patients without recurrence (19.5±17.1% vs. 8.2±6.7%, p<0.001). In the multivariate logistic regression model, PMV≥20% (upper tertile) was the only independent predictor of ablation success (OR=11.4, 95% CI 1.4-92.1, p=0.023). A PMV≥20% demonstrated a sensitivity of 41.5%, a specificity of 94.1%, a PPV of 96.7%, and an NPV of 34.0% for free of AF after CPVI.

Conclusions: We report a significant association between increased PMV and 6-month CPVI success. PMV may help to identify patients with very high likelihood of freedom of AF 6-months after CPVI.
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http://dx.doi.org/10.1016/j.jelectrocard.2014.11.011DOI Listing
November 2015
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