Cardiomyocyte Injury Following Acute Ischemic Stroke

Active, not recruiting

• Conditions: Stroke, Ischemic; Cardiac Complication

• Registration Number: NCT03892226
• Lead Sponsor: Charite University, Berlin, Germany

Brief Summary

The primary goal of the CORONA-IS study is to characterize stroke-associated acute myocardial injury (elevated hs-cardiac troponin) using different diagnostic examinations in order get a better understanding of it's underlying pathomechanisms.

Detailed Description

Myocardial injury (i.e. elevated cardiac troponin levels) is a frequent cardiac complication during the first few days after an ischemic stroke and is associated with a poor functional outcome. Myocardial injury represents one essential part of a broad spectrum of cardiac complications ranging to severe arrhythmia or heart failure. There is evidence that, in the majority of patients, the underlying mechanism of stroke-associated myocardial injury is not coronary-mediated myocardial ischemia but rather stroke-induced functional and structural interference in the central autonomic network. The investigators hypothesize that this causes a dysregulation of normal neuronal cardiac control leading to myocardial edema and stunning ('Stroke-Heart-Syndrome') CORONA-IS is a prospective, observational, single-centered cohort study that will recruit 300 patients with acute ischemic stroke. According to serial high sensitivity cTn levels during the first 24h after admission, patients will be assigned to three groups (no myocardial injury, chronic myocardial injury, acute myocardial injury). Study procedures include cardiovascular MRI and transthoracic echocardiography to visualize (transient) cardiac dysfunction and provide detailed tissue characterization, 20-minute Holter-monitoring with an analysis of specific autonomic markers, and a systematic bio-banking to study further mechanisms such as altered microRNA signatures. A follow-up for cardiovascular events will be conducted one year after enrolment to study long-term effects of stoke-associated myocardial injury.

The aim of the CORONA-IS study is to develop a better understanding of the characteristics and the pathophysiology of stroke-induced acute myocardial injury ('Stroke-Heart-Syndrome') in order to identify patients at risk and improve diagnostic and therapeutic procedures.

Study Timeline

• Study First Submitted: 2019-03-25
• Study First Submitted QC: 2019-03-26
• Study First Posted: 2019-03-27
• Study Start: 2019-04-01
• Primary Completion: 2023-12-31
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-19
• Last Update Posted: 2024-02-20
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• age over 18
• diagnosis of acute ischemic stroke and hospital admission within 48h after onset of the symptoms
• diagnosis based on visible DWI-lesion in MRI
• written informed consent by participant
• repeated measurement of high sensitive Troponin T within 24h of admission (hs-troponin T, Roche Elecsys®, 99. percentile, upper reference limit=14ng/l)

Exclusion Criteria

• Pregnancy and / or breast-feeding.
• Impaired renal function (eGFR < 30 ml/min/1,73 m^2)
• Contraindications to undergo MRI (i.e., mechanic heart valve, cardiac pacemaker, etc.)
• Persistent or permanent atrial fibrillation
• ST- elevation myocardial infarction
• History of coronary artery bypass surgery or percutaneous trans-luminal coronary angioplasty (PTCA) ≤ four weeks

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Rate of myocardial edema without late gadolinium enhancement (native T1, T2 mapping)	within five days of admission to hospital	diagnosed in cardiovascular MRI (CMR), conducted at the fourth/fifth day after onset of the ischemic stroke
Rate of myocardial fibrosis with late Gadolinium enhancement (LGE) and acute edema in CMR	within five days of admission to hospital	Rate of myocardial fibrosis with LGE and acute edema in CMR, suggesting a recent myocardial infarction (\<1 month). CMR conducted at the fourth/fifth day after onset of the ischemic stroke.
Rate of acute disturbance of microcirculation	within five days of admission to hospital	Rate of acute disturbance of microcirculation (measurement on the basis of oxygen extraction in cardiac MRI). CMR conducted at the fourth/fifth day after onset of the ischemic stroke.
Rate of impaired left ventricular function and transient impaired left ventricular function in transthoracic echocardiography	within seven days of admission to hospital	Rate of impaired left ventricular function (ejection fraction \<50%, reduced global longitudinal strain etc.) in the transthoracic echocardiography as well as higher rate of transient left ventricular dysfunction detected in repeated transthoracic echocardiography (TTE). The TTE will be conducted at the first day after enrolment as well as at the day before discharge or five days after the first TTE respectively.
Rate of signs of left ventricular dysfunction in the CMR	within five days of admission to hospital	Rate of signs of left ventricular dysfunction in the cardiac MRI (i.e. reduced ejection fraction, end diastolic left ventricular volume, longitudinal strain rate). CMR conducted at the fourth/fifth day after onset of the ischemic stroke.

Secondary Outcome Measures

Name	Time	Method
Rate of pathologic Periodic Repolarization Dynamics (PRDs) and Deceleration Capacity (DC)	within seven days of admission to hospital	Rate of Periodic Repolarization Dynamics (PRDs) and Deceleration Capacity (DC) in the 20 minutes Holter ECG as sign of enhanced sympathetic activity (PRD\> 5.75 deg\^2, DC ≤2.5 ms).
Difference in specific microRNA pattern in participants with myocardial damage induced by acute ischemic stroke	within seven days of admission to hospital	Analysis of circulating microRNA pattern via next generation Sequencing in patient's blood samples.
Functional outcome	at baseline, at seven days after baseline (or at day of discharge from hospital if <7d, respectively) and at twelve months after the initial event	functional outcome will be evaluated using the 'modified Rankin scale' (range from 0 = no symptoms to 6 = death; favorable outcome defined as 0 or 1 in the modified Rankin scale)
Rate of cardiovascular events	at one week and at twelve months after the initial event	cardiovascular events include new stroke, transient ischemic attack and myocardial infarction
Mortality	at one week and twelve months after the initial event	mortality (rate of deaths) will be recorded during the stay in hospital as well as after twelve months

Trial Locations

Locations (1)

Charité-Campus Benjamin Franklin; 🇩🇪 Berlin, Germany