Ethnicity and thrombolysis in ischemic stroke: a hospital based study in Amsterdam.

BACKGROUND: Ethnic differences have been reported with regard to several medical therapies. The aim of this study was to investigate the relation between ethnicity and thrombolysis in stroke patients. METHODS: Retrospective single-centre study. Patients admitted with an ischemic stroke between 2003 and 2008 were included. Ethnicity was determined by self-identification and stratified into white and non-white (all other ethnicities). The main outcome measure was the difference in thrombolysis rate between white and non-white patients. Logistic regression analysis was used to identify potential confounders of the relation between ethnicity and thrombolysis. RESULTS: 510 patients were included, 392 (77%) white and 118 (23%) non-white. Non-white patients were younger (median 69 vs. 60 years, p<0.001), had a higher blood pressure at admission (median systolic 150 vs. 160 mmHg, p=0.02) and a lower stroke severity (median NIHSS 5 vs. 4, p=0.04). Non-white patients were significantly less often treated with thrombolysis compared to white patients (odds ratio 0.34, 95% CI 0.17-0.71), which was partly explained by a later arrival at the hospital. After adjustment for potential confounders (late arrival, age, blood pressure above upper limit for thrombolysis, and oral anticoagulation use), a trend towards a lower thrombolysis rate in non-whites remained (adjusted odds ratio 0.38, 95% CI 0.13 to 1.16). CONCLUSIONS: Non-white stroke patients less often received thrombolysis than white patients, partly as a result of a delay in presentation. In this single centre study, potential bias due to hospital differences or insurance status could be ruled out as a cause. The magnitude of the difference is worrisome and requires further investigation. Modifiable causes, such as patient delay, awareness of stroke symptoms, language barriers and treatment of cardiovascular risk factors, should be addressed specifically in these ethnic groups in future stroke campaigns.

Cardiac ion channel mutations in the sudden infant death syndrome.

Sudden infant death syndrome (SIDS) is characterized by the sudden death of an infant that occurs during sleep and remains unexplained despite thorough examination. In addition to clinical associations such as prone sleeping and exposure to cigarette smoke, several genetic factors have been identified with regard to SIDS, including autonomic disorders, immunologic polymorphisms and metabolic disorders. In the past decade, postmortem genetic analysis ('molecular autopsy') of SIDS cases has revealed a number of cardiac ion channel mutations that are associated with arrhythmia syndromes, including the long QT syndrome, Brugada syndrome and short QT syndrome. Mutations have been found in genes encoding (subunits of) cardiac potassium, sodium and calcium channels, as well as in genes involved in the trafficking or regulation of these channels. Here, we review the literature on cardiac ion channel mutations in relation to SIDS. Combining data from population-based cohort studies, we conclude that at least one out of five SIDS victims carries a mutation in a cardiac ion channel-related gene and that the majority of these mutations are of a known malignant phenotype. Genetic analysis is therefore recommended in cases of sudden infant death. More research is required to further elucidate the pathophysiology of SIDS and to determine whether genetic or electrocardiographic screening of apparently healthy infants should be pursued.

Mechanism of right precordial ST-segment elevation in structural heart disease: excitation failure by current-to-load mismatch.

BACKGROUND: The Brugada sign has been associated with mutations in SCN5A and with right ventricular structural abnormalities. Their role in the Brugada sign and the associated ventricular arrhythmias is unknown. OBJECTIVE: The purpose of this study was to delineate the role of structural abnormalities and sodium channel dysfunction in the Brugada sign. METHODS: Activation and repolarization characteristics of the explanted heart of a patient with a loss-of-function mutation in SCN5A (G752R) and dilated cardiomyopathy were determined after induction of right-sided ST-segment elevation by ajmaline. In addition, right ventricular structural discontinuities and sodium channel dysfunction were simulated in a computer model encompassing the heart and thorax. RESULTS: In the explanted heart, disappearance of local activation in unipolar electrograms at the basal right ventricular epicardium was followed by monophasic ST-segment elevation. The local origin of this phenomenon was confirmed by coaxial electrograms. Neither early repolarization nor late activation correlated with ST-segment elevation. At sites of local ST-segment elevation, the subepicardium was interspersed with adipose tissue and contained more fibrous tissue than either the left ventricle or control hearts. In computer simulations entailing right ventricular structural discontinuities, reduction of sodium channel conductance or size of the gaps between introduced barriers resulted in subepicardial excitation failure or delayed activation by current-to-load mismatch and in the Brugada sign on the ECG. CONCLUSION: Right ventricular excitation failure and activation delay by current-to-load mismatch in the subepicardium can cause the Brugada sign. Therefore, current-to-load mismatch may underlie the ventricular arrhythmias in patients with the Brugada sign.