Atrial Cardiomyopathy Predicts the Functional Outcome and Mortality in Stroke Patients.

AIM: Atrial cardiomyopathy (ACM) is characterized by atrial dysfunction. This study aims to assess the prognostic significance of ACM in patients with noncardioembolic stroke (NCS). METHODS: Patients with NCS within seven days of onset were prospectively enrolled between January 2019 and December 2020. ACM was defined as either an N-terminal pro-brain natriuretic peptide (NT-pro BNP) ＞250 pg/ml or a P-terminal force in precordial lead V1 (PTFV1) ≥ 5000µV·ms. A poor functional outcome was determined as a score of 3-6 on the modified Rankin Scale (mRS) within a 2-year follow-up period. Logistic regression and Cox regression analyses were employed to examine the relationship between ACM and the long-term prognosis of patients with NCS. RESULTS: A total of 1,346 patients were enrolled, of whom 299 (22.2%) patients were diagnosed with ACM. A total of 207(15.4%) patients experienced a poor functional outcome, and 58 (4.3%) patients died. A multivariate logistic regression analysis indicated that ACM was significantly associated with a poor functional outcome in NCS patients [adjusted odds ratio (aOR): 2.01; 95% confidence interval (CI): 1.42-2.87; p＜0.001]. Additionally, a multivariate Cox regression analysis showed that an NT-pro BNP ＞250 pg/ml was significantly associated with an increased risk of all-cause mortality [adjusted hazard ratio (aHR), 2.51; 95% CI: 1.42-4.43; p=0.001]. CONCLUSIONS: ACM may serve as a novel predictor of a poor long-term functional outcome in patients with NCS. Elevated NT-pro BNP levels (＞250 pg/ml) were found to be associated with a higher risk of all-cause mortality. These findings warrant further validation in multicenter studies.

Cryptogenic stroke as a working diagnosis: the need for an early and comprehensive diagnostic work-up.

In the Nordic Atrial Fibrillation and Stroke (NOR-FIB) study, the causes of ischemic stroke were identified in 43% of cryptogenic stroke patients monitored with implantable cardiac monitor (ICM), but one-third of these patients had non-cardioembolic causes. These results suggest the need for an early and comprehensive diagnostic work-up before inserting an ICM.

Correlation between left atrial expansion index and stroke subtype: A 10-Year Follow-Up Study.

PURPOSE: Although left atrial (LA) expansion index predicts cardiovascular events, its efficacy for predicting cerebral events is unknown. METHODS: This study enrolled 2205 patients who had sinus rhythm after echocardiography in their first visit. LA expansion index was calculated as (Volmax -Volmin ) x100%/Volmin , where Volmax was defined as maximal LA volume and Volmin as minimal LA volume. The study endpoint was ischemic stroke. Stroke subtype was classified as cardioembolic stroke (CE), noncardioembolic stroke with determined mechanism (NCE), or embolic stroke of undetermined source (ESUS). RESULTS: Over a 10-year (mean 9.7 years) follow-up period, 128 (5.8%) participants reached endpoint, including 46 with CE, 33 with NCE, and 49 with ESUS. Regardless of stroke subtype, LA expansion index was lower in the event groups compared to the nonevent group. The lowest quartile of LA expansion index was associated with high CHA2 DS2 -VASc score at enrollment and more events, including CE, ESUS, atrial fibrillation (AF), heart failure, and all-cause mortality, relative to other quartiles. The LA expansion index was an independent predictor of CE (HR 0.82; 95% CI 0.723-0.912, per 10% increase in LA expansion index; P < .0001) and ESUS (HR 0.92; 95% CI 0.881-0.976, per 10% increase in LA expansion index; p 0.003). An LA expansion index <68% predicts the presence of AF after ESUS with 84% sensitivity and 70% specificity. CONCLUSION: LA expansion index is useful for predicting CE and ESUS. It is also associated with AF, heart failure hospitalization, and all-cause mortality.

Early and long-term outcomes of argatroban use in patients with acute noncardioembolic stroke.

BACKGROUND: Argatroban in acute noncardioembolic stroke ineligible for intravenous thrombolysis (IVT) or endovascular treatment (EVT) remains unclear. This study aimed to evaluate whether argatroban improved early and long-term outcomes compared with antiplatelet treatment. METHODS: This retrospective observational study, using the prospective stroke database from our hospital, included all consecutive patients who hospitalized from January 1, 2017 to December 31, 2019, with a diagnosis of acute non-cardioembolic stroke within 48 hours of stroke onset but not receiving IVT and EVT. Patients were divided into 2 groups: the argatroban group and the control group without argatroban. Outcome assessment with early neurological deterioration (END), National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), bleeding complications, and mortality were compared between the 2 groups in all cases and different stroke subtypes. An ordinal logistic regression analysis evaluated the association between argatroban use and mRS score at 90 days. RESULTS: Of 1325 patients were enrolled, 519 patients in the argatroban group and 806 in the control. Baseline characteristics, hospital bleeding complications, and 90-day mortality were similar for the 2 groups. The argatroban group showed lower END, larger improvement of 7-day NIHSS score and higher percentage of a 90-day mRS score of 02. Similar results were found in subgroup analysis with large-artery atherosclerosis, anterior circulation infarction, and moderate stroke. Also, argatroban use was significantly associated with an excellent long-term stroke outcome (mRS ≤ 2). CONCLUSION: The current study suggested that argatroban was safe and effective for improving short and long-term outcomes in noncardioembolic stroke patients.

Acute Aspirin Plus Cilostazol Dual Therapy for Noncardioembolic Stroke Patients Within 48 Hours of Symptom Onset.

Background The aim of the present study was to investigate the efficacy and safety of antiplatelet (aspirin plus cilostazol) dual therapy for patients with noncardioembolic stroke within 48 hours of symptom onset. Methods and Results The ADS (Acute Aspirin Plus Cilostazol Dual Therapy for Non-Cardiogenic Stroke Patients Within 48 Hours of Symptom Onset ) study is an investigator-initiated, prospective, multicenter (34 hospitals in Japan), randomized, open-label, and aspirin-controlled trial. Acute stroke patients with noncardioembolic stroke within 48 hours of onset were studied. The subjects were randomly allocated to combination therapy with aspirin 81 to 200 mg plus cilostazol 200 mg (dual group) and single therapy with aspirin 81 to 200 mg (aspirin group) for 14 days. After the 14 days, all patients took the cilostazol 200 mg for 3 months. A primary efficacy outcome was defined as any one of the following occurring (neurological deterioration, symptomatic stroke recurrence, or transient ischemic attack) within 14 days. A primary safety outcome included intracerebral hemorrhage and subarachnoid hemorrhage. Between May 2011 and June 2017, 1201 patients (796 [66%] men; median age, 69 [61-77] years) randomized 1:1 to either the dual group or the aspirin group were analyzed. Initial National Institutes of Health Stroke Scale score was 2 (1-4) in both groups (P=0.830). A primary efficacy outcome was observed in 11% in the dual group and 11% in the aspirin group (P=0.853). A primary safety outcome occurred in 2 (0.3%) in the dual group and in 1 (0.2%) in the aspirin group (P=0.624). Conclusions Dual antiplatelet therapy using cilostazol and aspirin was safe but did not reduce the rate of short-term neurological worsening. Clinical Trial Registration URL: umin.ac.jp/ctr/index/htm. Unique identifier: UMIN000004950.

Retrospective Analysis of Argatroban in 353 Patients with Acute Noncardioembolic Stroke.

BACKGROUND: Argatroban is a thrombin inhibitor agent for acute noncardioembolic ischemic stroke in Japan. We studied the prognosis in patients with acute stroke treated by argatroban in comparison with the control group with ozagrel in our hospital. SUBJECTS AND METHODS: A total of 513 patients with acute noncardioembolic ischemic stroke were enrolled retrospectively from our hospital database. Of all patients with stroke, 353 were administered with argatroban. The other 160 control patients were administered with ozagrel. The patients were examined as to their stroke types, the neurological severity according to the National Institutes of Health Stroke Scale (NIHSS), and clinical outcomes on discharge were determined according to the modified Rankin Scale (mRS). RESULTS: A total of 353 patients with acute noncardioembolic stroke, including 138 with lacunar infarction (LIs) and 215 with atherothrombotic infarction (ATI) showed functional recovery by argatroban, but the effectiveness of argatroban was not superior to ozagrel therapy defined by the control group. A total of 255 patients with ATI who were treated with both argatroban and ozagrel showed improvement by 1 point. We could not find any significant difference between argatroban and ozagrel in the 2 stroke subtypes, LI and ATI. We also found that combination therapy of argatroban and edaravone was not superior to argatroban monotherapy in clinical outcome. CONCLUSIONS: Argatroban therapy was not superior to control with ozagrel therapy in acute noncardioembolic ischemic stroke, including LI and ATI, regardless of the use of edaravone.

Heads and Tails of Natriuretic Peptides: Neuroprotective Role of Brain Natriuretic Peptide.

BACKGROUND: Besides the relevant role of brain-type natriuretic peptide (BNP) as biomarker of cardioembolic strokes, new experimental evidences suggest that this peptide may mediate neuroprotective effects. In this study, we have evaluated for the first time the clinical association between BNP (by means of proBNP) and good outcome in ischemic stroke patients, and analyzed the effect of blood BNP increase in an ischemic animal model. METHODS AND RESULTS: A retrospective study with 2 different cohorts (262 patients in cohort I and 610 in cohort II) from the same prospective stroke registry was performed. proBNP concentration was analyzed within the first 12 hours from stroke onset. The primary predictor variable was functional outcome evaluated by modified Rankin Scale at 3 months. For the experimental study, BNP pretreatment was tested in an ischemic animal model subjected to a transient occlusion of the cerebral artery, and the infarct volume and sensorimotor deficit were evaluated for 14 days. Cardioembolic strokes presented a positive correlation between proBNP concentration and modified Rankin Scale at 3 months; however, noncardioembolic strokes presented a negative correlation. In the logistic regression analysis, noncardioembolic strokes with concentrations of proBNP ≥340 pg/mL were associated with a good outcome. In line with these clinical findings, the experimental study revealed that those BNP pretreated animals presented a reduction on infarct volumes at 24 hours and functional recovery at days 7 and 14 compared with the control groups. CONCLUSIONS: These clinical and experimental evidences support the potential role of BNP as a protective factor against cerebral ischemia.

A pathological perspective on the natural history of cerebral atherosclerosis.

BACKGROUND: The natural history of intracranial large artery atherosclerosis has been mainly described from lumen-based imaging studies, and much of what is reported to be known about atherosclerosis is derived from non-cerebral arteries. AIMS: To test the hypothesis that atherosclerosis is only partially represented by stenosis and that advanced atherosclerosis is more common that severe stenosis in noncardioembolic infarcts. METHODS: Cerebral large arteries from 196 autopsy cases were studied. The revised American Heart Association classification for atherosclerosis was used to determine the phenotype in each available artery. Cross-sectional lumen stenosis was obtained as defined by the Glagov's method. RESULTS: As age of cases increased, there was a progressive increment in the frequency of atherosclerotic lesions, rising from 5% of all arteries at age 20-40, to more than 40% at age 60 or older. Stenosis also increased with age: less than 3% of the arteries in those ≤50 years had >40% stenosis, while one out of five arteries in those >80 years had >40% stenosis. In most cases (80%), atherosclerosis and stenosis were directly related. However, one out of five cases with advanced atherosclerosis had <30% stenosis. In arteries supplying brain areas with noncardioembolic infarcts, the majority of segments exhibiting advanced atherosclerosis had lumen stenosis of <40%. CONCLUSION: Although intracranial atherosclerosis is typically associated with stenosis, a substantial minority of cases shows advanced atherosclerosis in the absence of stenosis >40%. Definitions based solely on stenosis may underestimate the extent and role of intracranial large artery atherosclerosis.