Biomarkers of Cardiac Dysfunction as Risk Factors in Cryptogenic Stroke.

It is unclear whether biomarkers of cardiac dysfunction are associated with cryptogenic stroke (CS). We retrospectively evaluated consecutive ischemic stroke patients. Patients underwent transthoracic echocardiography to evaluate left atrial diameter and the peak transmitral filling velocity/mean mitral annular velocity during early diastole (E/e'). Patent foramen ovale (PFO) and left atrial appendage flow velocity were evaluated by transesophageal echocardiography. We compared clinical characteristics and biomarkers of cardiac dysfunction (brain natriuretic peptide [BNP], left atrial diameter, E/e', and left atrial appendage flow velocity) between CS or CS without large PFO and other causative stroke subtypes. Among 1,514 patients with ischemic stroke, 264 patients were classified as having CS. Of these, transesophageal echocardiography revealed 27/158 (17%) large PFOs. In comparison, for the noncardioembolic stroke group, which consisted of large artery and small vessel subtypes, patients with CS without large PFO had higher log10 BNP (adjusted OR 2.70; 95% CI 1.92-3.78; p < 0.001), higher log10 E/e' (3.41; 1.21-13.15; p = 0.019), and lower left atrial appendage flow velocity (0.98; 0.97-1.00; p = 0.031). Left atrial diameter was similar for noncardioembolic stroke and CS without large PFO (p = 0.380). Cutoff values of BNP, E/e', and left atrial appendage flow velocity capable of distinguishing CS without large PFO from noncardioembolic stroke were 65.0 pg/mL (sensitivity 55.3%; specificity 70.9%), 13.0 (45.5%; 68.0%), and 46.0 cm/s (37.1%; 87.5%), respectively. Patients with CS without large PFO could have biomarkers of cardiac dysfunction.

Tateishi Y ，Kanamoto T ，Yamashita K ，Hirayama T ，Yoshimura S ，Miyazaki T ，Tsuneto A ，Maemura K ，Morofuji Y ，Horie N ，Izumo T ，Shiraishi H ，Tsujino A ... -  《-》

Cardiac and Echocardiographic Markers in Cryptogenic Stroke with Incidental Patent Foramen Ovale.

Some cardiac abnormalities could be a substrate for potential embolic source in cryptogenic stroke (CS). We evaluated whether cardiac and echocardiographic markers were associated with CS in patients with incidental patent foramen ovale (PFO) as defined using the Risk of Paradoxical Embolism (RoPE) score. Among 677 patients enrolled in a multicenter observational CS registry, 300 patients (44%) had PFOs detected by transesophageal echocardiography. They were classified into probable PFO-related stroke (RoPE score>6, n = 32) and stroke with incidental PFO (RoPE score≤6, n = 268) groups, and clinical characteristics, laboratory findings, cardiac and echocardiographic markers (i.e. brain natriuretic peptide, left atrial [LA] diameter, ejection fraction, early transmitral flow velocity/early diastolic tissue Doppler imaging velocity [E/e'], LA appendage flow velocity, spontaneous echo contrast, atrial septal aneurysm, substantial PFO, and aortic arch plaques), stroke recurrence, and excellent outcome (modified Rankin scale score <2) at discharge were compared. Risk factors for low RoPE scores were determined using multiple logistic regression analysis. Higher brain natriuretic peptide levels (p = 0.032), LA enlargement (p < 0.001), higher E/e' (p = 0.001), lower LA appendage flow velocity (p < 0.001), non-substantial PFO (p = 0.021), and aortic arch plaques (p = 0.002) were associated with the low RoPE score group. Patients with high RoPE scores had excellent outcomes (58% versus 78%, p = 0.035). LA enlargement (age- and sex-adjusted odds ratio, 1.15; 95 % confidence interval, 1.00-1.32; p = 0.039) was an independent predictor of low RoPE scores. Abnormal cardiac substrate could be associated with CS occurrence in a subset of patients with PFO. Patients with CS who had incidental PFO may be at risk of cardioembolism.

Tateishi Y ，Ueno Y ，Tsujino A ，Kuriki A ，Kamiya Y ，Shimizu T ，Doijiri R ，Yamaguchi E ，Kikuno M ，Shimada Y ，Takekawa H ，Koga M ，Ihara M ，Hirata K ，Hasegawa Y ，Toyoda K ，Hattori N ，Urabe T ，CHALLENGE ESUS/CS collaborators ... -  《-》

Left Atrial Appendage Flow Velocity and Multiple Infarcts in Cryptogenic Stroke.

To validate the hypothesis that cryptogenic stroke with multiple infarcts included embolic stroke due to left atrial appendage (LAA) dysfunction, the present retrospective observational study was aimed to clarify the association between LAA flow velocity (LAA-FV) and multiple infarcts in patients with cryptogenic stroke. From consecutive patients with cryptogenic stroke admitted to our hospital within 7 days after onset, patients without brain magnetic resonance imaging (MRI) on admission or without transesophageal echocardiography (TEE) during acute hospitalization were excluded, and the remaining patients were enrolled. Multiplicity of fresh infarcts was assessed using diffusion-weighted images from brain MRI. LAA-FV was defined as LAA peak emptying flow velocity on TEE. Of 786 enrolled patients, 522 patients (66%) had a single infarct, and the remaining 264 patients (34%) had multiple infarcts. The percentage of multiple infarcts decreased with increasing quartiles of LAA-FV (p for trend <0.001). The adjusted odds ratio for multiple infarcts decreased with increasing quartiles of LAA-FV (adjusted odds ratio in the fourth quartile, 0.39; 95% confidence interval, 0.25-0.60; compared with the first quartile). LAA-FV as a continuous variable was negatively associated with multiple infarcts (adjusted odds ratio per 10 cm/s, 0.87; 95% confidence interval, 0.81-0.92). Reduced LAA-FV on TEE was associated with multiple infarcts in patients with cryptogenic stroke. The present findings indicate that cryptogenic stroke with multiple infarcts includes embolic stroke due to LAA dysfunction.

Tokunaga K ，Hashimoto G ，Mizoguchi T ，Mori K ，Shijo M ，Jinnouchi J ，Kuwashiro T ，Yasaka M ，Kitazono T ，Okada Y ... -  《-》

Brain natriuretic peptide as a surrogate marker for cardioembolic stroke with paroxysmal atrial fibrillation.

Cardioembolic stroke generally results in severer disability, since it typically has a larger ischemic area than the other types of ischemic stroke. However, it is difficult to differentiate cardioembolic from noncardioembolic stroke (atherothrombotic and lacunar stroke), whenever ischemic stroke patients have sinus rhythm at the time of presentation. In this study, we evaluated the levels of plasma brain natriuretic peptide in acute ischemic stroke patients with cardioembolic or noncardioembolic stroke and assessed whether this could provide a basis for differentiating cardioembolic stroke (especially due to paroxysmal atrial fibrillation) from noncardioembolic stroke. Our patient cohort consisted of 99 consecutive patients with acute cerebral infarction who were admitted to Kagawa University School of Medicine Hospital from January 1, 2005, to December 31, 2006. We excluded 23 patients with valve disease, heart failure, myocardial infarction or chronic renal failure. The mean age of the remaining 76 patients (51 males, 25 females) was 70.0 +/- 10.1 years. Thirty-six patients had cardioembolic stroke with atrial fibrillation (including permanent and paroxysmal atrial fibrillation); the remaining 40 had noncardioembolic stroke. The plasma brain natriuretic peptide was evaluated on the first morning after admission in all patients. In cardioembolic stroke with atrial fibrillation (permanent and paroxysmal atrial fibrillation), the plasma brain natriuretic peptide, ratio of peak early filling velocity to peak atrial systolic velocity (E/A) and left atrial diameter were significantly increased (p < 0.001), and the left atrial appendage flow was significantly decreased (p < 0.001), compared with noncardioembolic stroke. Analyzed in those 4 factors, cardioembolic stroke was strongly predicted with >95% accuracy assessed by plasma brain natriuretic peptide and left atrial appendage flow. From our results, it was suggested that the first-day brain natriuretic peptide and left atrial appendage flow measurements would be helpful in differentiating cardioembolic stroke with atrial fibrillation from noncardioembolic stroke.

Naya T ，Yukiiri K ，Hosomi N ，Takahashi T ，Ohkita H ，Mukai M ，Koziol JA ，Kohno M ... -  《-》

Atrial dyssynchrony and left atrial stiffness are risk markers for cryptogenic stroke in patients with patent foramen ovale.

The clinical and echocardiographic parameters associated with the risk predictors of cryptogenic stroke (CS) in patients with patent foramen ovale (PFO) still diverse and with a great debate. We hypothesized that left atrial stiffness (LASt) and atrial dyssynchrony may increase the risk of CS in patients with PFO. A total of 129 consecutive patients presented without clinical reasoning of stroke were recruited. Transesophageal echocardiographic assessment was performed to investigate the presence of PFO. PFO was identified in 52% (group I) and absent in 48% (group II). Utilizing speckle-tracking imaging LASt and atrial dyssynchrony was evaluated among patients with PFO (group I) vs those without PFO (group II). LASt was significantly increased in group I patients compared with group II (P < .001). Likewise patients with PFO had a significant LA dyssynchrony compared with those in group II (P < .001). Interatrial dyssynchrony and left atrial dyssynchrony were correlated with LASt (r = .47 and 0.51, respectively; P < .001). Cardiac arrhythmias were significantly encountered in group I patients (at presentation and with Holter monitoring) P < .001. Besides significantly increase in atrial dyssynchrony and in LASt in patients with arrhythmias compared with those without (P < .001). ROC analysis revealed that LASt index ≥ 0.61 and LA dyssynchrony ≥ 23.5 predicts cardiac arrhythmias in CS patients with PFO with (AUC: 0.85 and 0.87, respectively, P < .001). In conclusion, we demonstrated that LASt and atrial dyssynchrony might be risk markers of cryptogenic stroke in patients with PFO.

Mahfouz RA ，Alawady WS ，Salem A ，Abdelghafar AS ... -  《-》