Lethal immunoglobulins: Autoantibodies and sudden cardiac death.

Sudden cardiac death (SCD) is an unexpected death due to cardiac causes that occurs in a short time period (generally within 1 h of symptom onset) in a person with known or unknown cardiac disease. Patients with cardiomyopathies, myocarditis, ischemic heart disease and cardiac channelopathies are at risk of SCD. However, a certain percentage of autopsy-negative cases of SCD in the young (<35 years) remain unexplained even after a post-mortem genetic testing. Autoantibodies against cardiac proteins may be potentially involved in the pathogenesis of different heart diseases and in the occurrence of unexplained SCD. In this review we analyze clinical and animal studies that elucidate the prevalence of these autoantibodies in patients with different cardiac diseases and their pathophysiological relevance. We propose a classification of the autoantibodies associated with heart diseases and focus on their molecular and cellular effects. Anti-beta adrenergic receptor antibodies and anti-muscarinic acetylcholine receptor antibodies affect myocardial electrophysiological properties and were reported to be the independent predictors of SCD in patients with different heart diseases. Autoimmune mechanism is proposed for cardiac-related adverse reactions following human papillomavirus (HPV) vaccination. The pentapeptid sharing between HPV's antigens, adrenergic receptors and muscarinic acetylcholine receptors supports this assumption. The dysregulating effects of the autoantibodies against calcium and potassium ion channels can be the basis for autoimmune phenocopies of genetic cardiac channelopathies, which are also associated with SCD.

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.

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.