Indici elettrocardiografici in pazienti affetti da attacco ischemico transitorio (TIA) e ictus ischemico nello studio di popolazione OXVASC

Parte 1 BACKGROUND: One-third of TIA and ischaemic strokes are of undetermined aetiology (cryptogenic). It has been previously shown that cryptogenic events had fewest atherosclerotic markers and no excess of long-term risks of new AF or recurrent cardioembolic stroke or systemic embolism. Another emerging hypothesis suggests that atrial cardiopathy could be a risk factor for thromboembolism independent of underlying arrhythmia. Therefore in the current study, we aimed to determine the prevalence of electrocardiogram (ECG) makers of atrial function in ischaemic stroke subtypes. METHODS: In a population-based study in Oxfordshire, UK, among patients with a first TIA or ischaemic stroke from 2002-2015, we compared cryptogenic events versus other aetiological subtypes (TOAST classification). We studied ECG markers of atrial function (P wave inconsistency, maximum P wave duration, P wave dispersion, and RR interval variation) and echocardiographic makers of atrium structure (enlargement of the left atrium-LA). FINDINGS: Of 2213 eligible patients, 812 (36.7%) had cryptogenic events. As expected, patients with cardioembolic events were significantly more likely to have enlarged LA on echocardiogram compared to patients with non-cardioembolic events (p<0.0001). However, the prevalence of enlarged LA did differ in patients with cryptogenic events vs. patients with large artery/smal vessel disease (24.3% vs. 24.0%, p=0.93). Among the 1881 patients in sinus rhythm on ECG at baseline, although compared to patients with cardioembolic events, the prevalence of ECG markers of atrial function in patients with cryptogenic events were significantly lower (all p<0.0001), compared to patients with large artery/small vessel disease, patients with cryptogenic events had a significantly higher prevalence of P wave inconsistency (cryptogenic vs. large artery/small vessel –p<0.0001), P wave dispersion (≥60ms, p=0.01) and RR interval variation (≥80ms, p<0.0001). Results were consistent for analyses when paroxysmal AF episodes from prolonged cardiac monitoring were not included for aetiological classification, and when stratified by age groups, or excluding patients with TIA. INTERPRETATION: Compared to patients with large artery or small vessel stroke/TIA, patients with cryptogenic events have a higher prevalence of ECG markers of abnormal atrial function, with no excess of significant left atrium structure abnormality or new AF. Parte 2 BACKGROUND: Little is known about the relationship between QTc interval and incident stroke. Prolonged QTc has been reported in 38% to 71% of patients during acute stroke (the most frequent ECG abnormality in this setting). The pathophysiology of this phenomenon has not been elucidated. The autonomic dysfunction has been suggested as one of potential mechanism, however, it is also possible that prolonged QTc ante data the development of stroke and its presence during the acute phase reflects a higher risk for recurrent stroke, death and unfavourable outcome METHODS: In a population-based study in Oxfordshire, UK, among patients with a first TIA or ischaemic stroke from 2002-2015, we measured manually the QT interval in precordial leads. The absolute QT interval was adjusted for heart rate by using the Bazett’s formula. The QTc interval was defined as “prolonged” based on the widely accepted values in relation to sex categories. The aims of the study were: to evaluate the association between the prolongation of QTc and risk of recurrent stroke, death, myocardial infarction and the severity of the event; to investigate the possible aetiological mechanism analysing the association with dementia pre-event, blood pressure variation and white matter disease detected on brain CT or MRI. FINDINGS: Of 2213 eligible patients, 2132 had QTc measurement. We found a significant association between the prolonged QTc and recurrent stroke (p<0.0001, age-adjusted and sex-adjusted p<0.0001), recurrent myocardial infarction (p<0.0001, age-adjusted and sex-adjusted p<0.0001), death (p<0.0001, age-adjusted and sex-adjusted p<0.0001) at 3 months and 10 years follow up and the severity of stroke (p<0.0001, age-adjusted and sex-adjusted p<0.0001) classified according to NIHSS at the event. After exclusion of prolonging QTc drugs, heart disease, cardiac pacing, AF, electrolyte disturbance and complete BBB the relation remained unchanged. A prolonged QTc was significant associated with dementia (p<0.0001, age-adjusted and sex-adjusted p<0.0001); white matter disease measured using a visual scale on a brain MRI (p<0.0001, age-adjusted and sex-adjusted p= 0.041) or brain CT (p= <0.0001, age-adjusted and sex-adjusted p=0.033), and blood pressure variation calculated using the blood pressure measurements in the 5 years before the event (p= 0.0009, age-adjusted and sex-adjusted p=0.0001). INTERPRETATION: QT prolongation is a predictive marker of recurrent cerebrovascular events, cardiac morbidity and mortality in patients with a first TIA or ischaemic stroke .