P-wave characteristics as electrocardiographic markers of atrial abnormality in prediction of incident atrial fibrillation - The Malmö Preventive Project.

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.

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

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.

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

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.

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).

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 V1 (PTF-V1) as a marker of LA abnormality. A PTF-V1 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-V1. Normal PTF-V1 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-V1 (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-V1 bears additive prognostic information in the context of CRT, thus further strengthening the role of electrocardiographic diagnostics in risk stratification of patients with HF.

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

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.

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

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.

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

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/m2 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/m2 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 .

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

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.

Atrial fibrillation in patients with ischaemic stroke in the Swedish national patient registers: how much do we miss?

AIMS: Data from national discharge registers are commonly used to estimate prevalence and incidence of atrial fibrillation (AF) in epidemiology studies. However, sensitivity and specificity of register-based AF diagnosis have not been evaluated. We sought to assess the validity of AF diagnosis in the Swedish Patient Register against electrocardiography (ECG) documentation of AF. METHODS AND RESULTS: The study sample comprised of 336 patients [median age 76 (interquartile range (IQR) 67-82 years, 136 female] with first-ever ischaemic stroke, enroled in the Lund Stroke Register from March 2001 to February 2002 and 1 : 1 age- and gender-matched control subjects without stroke from the population register. Data was exported from the patient register in October 2011 (the end of follow-up). Atrial fibrillation documentation by ECG was assessed using an electronic archive containing all ECGs taken in the hospital catchment area starting in 1988. A total of 7247 ECGs were reviewed, with the median number of ECGs per person being 7.5 (IQR 3-15). Atrial fibrillation was detected by ECG in 190 patients; and in 188 patients by linkage with patient register. In most patients, AF was documented first by ECG data, with median time to register diagnosis being 16 days (IQR 3-859). Specificity of AF diagnosis in the Swedish Patient Register was 93%, sensitivity was 80%. CONCLUSION: Despite the high specificity, AF diagnosis in the Swedish Patient Register assessed in the population of ischaemic stroke patients and age- and gender-matched control subjects has modest sensitivity, which may result in underestimating prevalent and incident AF cases if only register data are used for identification of subjects with AF in epidemiology studies.