Cardiomyocyte Injury Following Acute Ischemic Stroke

Stroke, Ischemic Clinical Trial

— CORONA-IS  

Official title:

Cardiomyocyte Injury Following Acute Ischemic Stroke

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03892226
• Other study ID #: EA4/123/18
• Status: Active, not recruiting
• Start date: April 1, 2019
• Est. completion date: December 2024

Study information

• Verified date: February 2024
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 300
• Est. completion date: December 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Complication
• Ischemia
• Ischemic Stroke
• Stroke
• Stroke, Ischemic

Locations

Country	Name	City	State
Germany	Charité-Campus Benjamin Franklin	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

References & Publications (5)

Mochmann HC, Scheitz JF, Petzold GC, Haeusler KG, Audebert HJ, Laufs U, Schneider C, Landmesser U, Werner N, Endres M, Witzenbichler B, Nolte CH; TRELAS Study Group. Coronary Angiographic Findings in Acute Ischemic Stroke Patients With Elevated Cardiac Troponin: The Troponin Elevation in Acute Ischemic Stroke (TRELAS) Study. Circulation. 2016 Mar 29;133(13):1264-71. doi: 10.1161/CIRCULATIONAHA.115.018547. Epub 2016 Mar 1. — View Citation

Rizas KD, Hamm W, Kaab S, Schmidt G, Bauer A. Periodic Repolarisation Dynamics: A Natural Probe of the Ventricular Response to Sympathetic Activation. Arrhythm Electrophysiol Rev. 2016 May;5(1):31-6. doi: 10.15420/aer.2015:30:2. — View Citation

Scheitz JF, Nolte CH, Doehner W, Hachinski V, Endres M. Stroke-heart syndrome: clinical presentation and underlying mechanisms. Lancet Neurol. 2018 Dec;17(12):1109-1120. doi: 10.1016/S1474-4422(18)30336-3. Epub 2018 Oct 26. — View Citation

Scheitz JF, Stengl H, Nolte CH, Landmesser U, Endres M. Neurological update: use of cardiac troponin in patients with stroke. J Neurol. 2021 Jun;268(6):2284-2292. doi: 10.1007/s00415-020-10349-w. Epub 2020 Dec 29. Erratum In: J Neurol. 2021 Feb 25;: — View Citation

Stengl H, Ganeshan R, Hellwig S, Blaszczyk E, Fiebach JB, Nolte CH, Bauer A, Schulz-Menger J, Endres M, Scheitz JF. Cardiomyocyte Injury Following Acute Ischemic Stroke: Protocol for a Prospective Observational Cohort Study. JMIR Res Protoc. 2021 Feb 5;10(2):e24186. doi: 10.2196/24186. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of myocardial edema without late gadolinium enhancement (native T1, T2 mapping)	diagnosed in cardiovascular MRI (CMR), conducted at the fourth/fifth day after onset of the ischemic stroke	within five days of admission to hospital
Primary	Rate of myocardial fibrosis with late Gadolinium enhancement (LGE) and acute edema in CMR	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.	within five days of admission to hospital
Primary	Rate of signs of left ventricular dysfunction in the CMR	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.	within five days of admission to hospital
Primary	Rate of acute disturbance of microcirculation	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.	within five days of admission to hospital
Primary	Rate of impaired left ventricular function and transient impaired left ventricular function in transthoracic echocardiography	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.	within seven days of admission to hospital
Secondary	Rate of pathologic Periodic Repolarization Dynamics (PRDs) and Deceleration Capacity (DC)	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).	within seven days of admission to hospital
Secondary	Difference in specific microRNA pattern in participants with myocardial damage induced by acute ischemic stroke	Analysis of circulating microRNA pattern via next generation Sequencing in patient's blood samples.	within seven days of admission to hospital
Secondary	Mortality	mortality (rate of deaths) will be recorded during the stay in hospital as well as after twelve months	at one week and twelve months after the initial event
Secondary	Functional outcome	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)	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
Secondary	Rate of cardiovascular events	cardiovascular events include new stroke, transient ischemic attack and myocardial infarction	at one week and at twelve months after the initial event