Natriuretic peptides for the detection of paroxysmal atrial fibrillation in patients with cerebral ischemia--the Find-AF study.

BACKGROUND AND PURPOSE: Diagnosis of paroxysmal atrial fibrillation (AF) can be challenging, but it is highly relevant in patients presenting with sinus rhythm and acute cerebral ischemia. We aimed to evaluate prospectively whether natriuretic peptide levels and kinetics identify patients with paroxysmal AF. METHODS: Patients with acute cerebral ischemia were included into the prospective observational Find-AF study. N-terminal pro brain-type natriuretic peptide (NT-proBNP), brain-type natriuretic peptide (BNP) and N-terminal pro atrial-type natriuretic peptide (NT-proANP) plasma levels were measured on admission, after 6 and 24 hours. Patients free from AF at presentation received 7 day Holter monitoring. We prospectively hypothesized that patients presenting in sinus rhythm with NT-proBNP>median were more likely to have paroxysmal AF than patients with NT-proBNP<median. RESULTS: 281 patients were included, of whom 237 (84.3%) presented in sinus rhythm. 220 patients naïve to AF with an evaluable prolonged Holter ECG were analysed. In patients with NT-proBNP>median (239 pg/ml), 17.9% had paroxysmal AF in contrast to 7.4% with NT-proBNP<239 pg/ml (p = 0.025). The ratio of early (0 h) to late (24 h) plasma levels of NT-proBNP showed no difference between both groups. For the detection of paroxysmal atrial fibrillation, BNP, NT-proBNP and NT-proANP at admission had an area under the curve in ROC analysis of 0.747 (0.663-0.831), 0.638 (0.531-0.744) and 0.663 (0.566-0.761), respectively. In multivariate analysis, BNP was the only biomarker to be independently predictive for paroxysmal atrial fibrillation. CONCLUSIONS: BNP is independently predictive of paroxysmal AF detected by prolonged ECG monitoring in patients with cerebral ischemia and may be used to effectively select patients for prolonged Holter monitoring

Excessive Supraventricular Ectopic Activity Is Indicative of Paroxysmal Atrial Fibrillation in Patients with Cerebral Ischemia

<div><p>Background</p><p>Detecting paroxysmal atrial fibrillation (PAF) in patients with cerebral ischemia is challenging. Frequent premature atrial complexes (PAC/h) and the longest supraventricular run on 24-h-Holter (SV-run_{24 h}), summarised as excessive supraventricular ectopic activity (ESVEA), may help selecting patients for extended ECG-monitoring, especially in combination with echocardiographic marker LAVI/a’ (left atrial volume index/late diastolic tissue Doppler velocity).</p><p>Methods</p><p>Retrospective analysis from the prospective monocentric observational trial Find-AF (ISRCTN-46104198). Patients with acute stroke or TIA were enrolled at the University Hospital Göttingen, Germany. Those with sinus rhythm at presentation received 7-day Holter-monitoring. ESVEA was quantified in one 24-hour interval free from PAF. Echocardiographic parameters were assessed prospectively.</p><p>Results</p><p>PAF was detected in 23/208 patients (11.1%). The median was 4 [IQR 1; 22] for PAC/h and 5 [IQR 0; 9] for SV-run_{24 h}. PAF was more prevalent in patients with ESVEA: 19.6% vs. 2.8% for PAC/h >4 vs. ≤4 (p<0.001); 17.0% vs. 4.9% for SV-run_{24 h} >5 vs. ≤5 beats (p = 0.003). Patients with PAF showed more supraventricular ectopic activity: 29 PAC/h [IQR 9; 143] vs. 4 PAC/h <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067602#pone.0067602-Kirchhof1" target="_blank">[1]</a>; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067602#pone.0067602-Engstrm1" target="_blank">[14]</a> and longest SV-run_{24 h} = 10 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067602#pone.0067602-Stahrenberg1" target="_blank">[5]</a>; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067602#pone.0067602-Capucci1" target="_blank">[21]</a> vs. 0 [0; 8] beats (both p<0.001). Both markers discriminated between the PAF- and the Non-PAF-group (area under receiver-operator-characteristics-curve 0.763 [95% CI 0.667; 0.858] and 0.716 [0.600; 0.832]). In multivariate analyses log(PAC/h) and log(SV-run_{24 h}) were independently indicative of PAF. In Patients with PAC/h ≤4 and normal LAVI/a’ PAF was excluded, whereas those with PAC/h >4 and abnormal LAVI/a’ showed high PAF-rates.</p><p>Conclusions</p><p>ESVEA discriminated PAF from non-PAF beyond clinical factors including LAVI/a’ in patients with cerebral ischemia. Normal LAVI/a’+PAC/h ≤4 ruled out PAF, while prevalence was high in those with abnormal LAVI/a’+PAC/h >4.</p></div

Clinical Characteristics.

<p>Clinical Characteristics.</p

ROC-curves – ESVEA as a predictor of PAF.

<p>ROC-curves for PAC/h (blue) and SV-run_{24 h} (green) to detect paroxysmal atrial fibrillation A) in baseline 7-day Holter-monitoring only or B) total PAF after baseline 7-day Holter-monitoring and clinical follow-up (up to 1 year).</p

PAF detection on 7-day holter in relation to PACs on 24-hour-Holter.

<p>Percentage of patients with paroxysmal atrial fibrillation on 7-day Holter-monitoring across quartiles of PACs/h detected within a 24-hour episode free from PAF.</p

Flow diagram.

<p>Flow diagram of patients included in ESVEA analysis within the Find-AF trial. 281 were included in the Find-AF trial, 237 without AF at presentation received 7-day Holter-ECG-monitoring. 229 Holter-ECGs were analysed. ESVEA analysis was possible in 208 cases, 23 of which showed at least one episode of PAF.</p

Duration of PAF episodes.

<p>Distribution of patients with longest episode of atrial fibrillation in 7-day Holter-monitoring in the respective category. Divisions were chosen based on trials indicating an increased thromboembolic risk above the respective cut-off: 6 min. as shown to increase stroke risk within the ASSERT-trial <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067602#pone.0067602-Healey1" target="_blank">[24]</a>, 6 hours (5.5 hours) as presented by the TRENDS-study investigators <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067602#pone.0067602-Glotzer1" target="_blank">[28]</a> and 24 hours as identified within the Italian AT-500 registry <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067602#pone.0067602-Capucci2" target="_blank">[29]</a>. 30 seconds as defined as minimal duration of atrial fibrillation by current AF guidelines <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067602#pone.0067602-Camm1" target="_blank">[30]</a>.</p

Patient characteristics.

†<p>Minor stroke resolved completely within 30 days or change in NIH stroke scale by 3 points; major stroke neurologic deficit persisted after 30 days and increased NIH stroke scale by 3 points.</p><p>ARB: Angiotensin receptor blocker.</p

NT-proBNP and NT-proBNP ratio and paroxysmal atrial fibrillation.

<p>Left panel: Percentage of study participants with paroxysmal atrial fibrillation on Holter monitoring in the two sub-groups of patients with NT-proBNP plasma levels below and above the median NT-proBNP plasma level (239 pg/ml). Right panel: Percentage of study participants with paroxysmal atrial fibrillation below and above the median ratio of early (0 h) to late (24 h) NT-proBNP plasma level (0.78).</p