Left Ventricular Diastolic Dysfunction as Predictor of Unfavorable Prognosis After ESUS.

OBJECTIVE: Identification of echocardiographic, hemodynamic and biochemical predictors of unfavorable prognosis after embolic strokes of undetermined etiology (ESUS) in patients at age <65. PATIENTS AND METHODS: Out of 520 ischemic stroke patients we selected 64 diagnosed with ESUS and additional 36 without stroke but with similar risk profile. All patients underwent echocardiography, non-invasive assessment of hemodynamic parameters using SphygmoCor tonometer and measurements of selected biomarkers. Follow-up time was 12 months. RESULTS: Nine percent of patients died, and recurrent ischemic stroke occurred in 9% of patients only in the ESUS group. Atrial fibrillation (AF) occurred in 10% of patients and the ESUS group had a significantly poorer outcome of AF in the first 2 months after hospitalization. The outcome of re-hospitalization was 28% in the ESUS group and 17% in the control group. In the multivariate analysis mean early diastolic (E') mitral annular velocity (OR 0.75, 95% CI: 0.6-0.94; p=0.01) was significantly associated with cardiovascular hospitalizations. The only independent predictor of recurrent stroke was the ratio of peak velocity of early diastolic transmitral flow to peak velocity of early diastolic mitral annular motion (E/E') (OR 0.75, 95% CI: 0.6-0.94; p=0.01). E/E' was independently associated with composite endpoint (death, hospitalization and recurrent stroke) (OR 1.90, 95% CI 1.1-3.2, p=0.01). CONCLUSION: The indices of diastolic dysfunction are significantly associated with unfavorable prognosis after ESUS. There is a robust role for outpatient cardiac monitoring especially during the first 2 months after ESUS to detect potential AF.

Arterial Stiffness and Indices of Left Ventricular Diastolic Dysfunction in Patients with Embolic Stroke of Undetermined Etiology.

PURPOSE: The study is aimed at identifying echocardiographic and circulating biomarkers as well as hemodynamic indices of embolic stroke of undetermined etiology (ESUS) in patients aged <65. METHODS: We prospectively investigated 520 patients with confirmed ischemic stroke and selected those 65 patients who were diagnosed with ESUS (age 54 (47-58) years, 42% male). An additional 36 without stroke but with a similar risk profile were included as a control group (age 53 (47-58) years, 61% male). All patients underwent echocardiography, noninvasive assessment of hemodynamic parameters using a SphygmoCor tonometer (AtCor Med., Australia), and measurements of selected biomarkers. RESULTS: ESUS patients and controls were well matched for baseline characteristics including blood pressure and left ventricular ejection fraction (LVEF). Compared to controls, patients with ESUS had lower mean early diastolic (E') and systolic (S') mitral annular velocities and a higher ratio of the peak velocity of early diastolic transmitral flow to the peak velocity of early diastolic mitral annular motion (all p < 0.01). The peak velocity flow in the late diastole (A wave) value and LV mass indexed to the body surface area (LVMI) (g/m2) were higher in the ESUS group than in the control group (both p < 0.01). The isovolumetric relaxation time (IVRT) was longer and the mean left atrial volume index (LAVI) was higher in ESUS patients compared to the control group. Parameters of arterial stiffness such as augmentation pressure, augmentation index, and augmentation index adjusted to a heart rate of 75 bpm (AIx75) were higher in ESUS patients compared to controls (p < 0.05). Patients in the ESUS group had higher levels of asymmetric dimethylarginine, interleukin 6, and N-terminal probrain natriuretic peptide (NT-proBNP, all p < 0.05) than those in the control group. In multivariate analysis, the following factors were significantly associated with the presence of ESUS: AIx75 (odds ratio (OR) 1.095, 95% confidence interval (CI) 1.004-1.194; p = 0.04), IVRT (OR 1.045, 95% CI: 1.009-1.082; p = 0.014), LAVI (OR 1.3, 95% CI: 1.099-1.537; p = 0.002), and NT-proBNP (OR 1.003, 95% CI: 1.001-1.005; p = 0.005). CONCLUSIONS: Increased arterial stiffness and indices of diastolic dysfunction as well as a higher NT-proBNP level are significantly associated with ESUS. These parameters require further scrutiny over time to understand their impact on the development of symptomatic heart failure. The ClinicalTrials.gov identifier is NCT03377465.

The potential role of inflammation in cryptogenic stroke.

PURPOSE: The study aimed to identify biomarkers predictive of cryptogenic stroke in patients aged <65. MATERIALS AND METHODS: We investigated 520 patients with ischemic stroke. Out of them we assigned 65 patients to the cryptogenic stroke group (age 54 (47-58), 42% male) and 36 without stroke to the control group (age 53 (47-58), 61% male). In all patients we assessed carotid intima-media thickness (cIMT) and the levels of biomarkers which might be involved in the underlying biological mechanism of ischemic stroke. RESULTS: There were no differences between stroke and control groups in the levels of syndecan 4, resistin, leptin, low-density lipoprotein cholesterol, triglycerides, prothrombin time, or activated partial thromboplastin time. There was no statistically significant difference in cIMT between groups. The level of high-density lipoprotein cholesterol was statistically significantly lower in the cryptogenic stroke group than in the controls (1.1 mmol/L (0.95-1.46) vs 1.37 (1.19-1.6) p = 0.02). Patients in the stroke group had higher levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) (391 pg/ml (107-1249) vs 109 (46-236); p = 0.003), interleukin 6 (2.6 pg/ml (0.8-8.1) vs 0.7 (0.4-1.2) p = 0.002) and asymmetric dimethylarginine (ADMA) (0.44 µmol/L (0.39-0.55) vs 0.36 (0.32-0.4); p = 0.0002) than the control group. In the multivariate analysis Il-6 was the only biomarker statistically significant associated with the occurrence of cryptogenic stroke (odds ratio 1.918, 95% confidence interval 1.029-3.575; p = 0.04). CONCLUSIONS: Endothelial dysfunction assessed by increased level of ADMA affects the inflammatory state in patients with cryptogenic stroke. Increase in the inflammatory cytokine IL-6 by 1 pg/ml almost doubles the risk of stroke.

Established and potential echocardiographic markers of embolism and their therapeutic implications in patients with ischemic stroke.

Cardiogenic strokes comprised 11% of all strokes and 25% of ischemic strokes. An accurate identification of the cause of stroke is necessary in order to prepare an adequate preventive strategy. In this review the confirmed and potential causes of embolic strokes are presented, which can be detected in echocardiography in the context of present treatment guidelines and gaps in evidence. There remains a need for further studies assessing the meaning of potential cardiac sources of embolism and establishment of rules for optimal medical prevention (antiplatelet therapy [APT] vs. oral anticoagulation [OAC]) and interventional procedures to reduce the incidence of ischemic strokes. Currently available data does not provide definitive evidence on the comparative benefits of OAC vs. APT in patients with cryptogenic stroke or embolic stroke of undetermined source. There is a lack of antithrombotic treatment scheme in the time between stroke and the completed diagnosis of potential sources of thromboembolism.

Cytisine - From the Past to the Future.

INTRODUCTION: Neuronal nicotinic acetylcholine receptors are ligand-gated ion channel receptors, distributed throughout central nervous system, as well as in peripheral ganglia and some non-neuronal cells. Cytisine, a qulinolizidine alkaloid, could be considered a high affinity ligand of those receptors. It is a partial agonist of ß2*-containing receptors and a full agonist of α7 and ß4*-containing receptors. Current indication: At present, pharmacodynamic properties of cytisine are leveraged only in a few European countries where it is available as medicinal product (Desmoxan and Tabex) indicated in the pharmacotherapy of nicotine addiction. Cytisine mimics the influence of nicotine on α4ß2* receptors, but with higher affinity and lower activity. It lowers rewarding and reinforcing effects of nicotine in smoking persons and reduces withdrawal symptoms and craving in quitting ones. Potential indications: The results of non-clinical studies suggest that cytisine could affect ethanol consumption, has an antidepressant and neuroprotective effect and could be useful in reducing body mass and preventing weight gain. Although there is a lack of research on cytisine in the treatment of areca nuts usage, the preliminary data suggest its usefulness. The combination of cytisine and Trolox C was selected as a possible effective treatment for type 2 diabetes. Though these drugs alone are not effective, their theoretical usefulness was confirmed in animal models. SUMMARY: Treatment with cytisine is an effective, cost-efficient, affordable and well tolerated nicotine addiction therapy. Potential new indications for cytisine include the treatment of alcoholism, areca nuts usage, Parkinson's disease, an autonomic-system failure. Further studies are necessary.