Clinical trial NCT03892226: Cardiomyocyte Injury Following Acute Ischemic Stroke
Official title: Cardiomyocyte Injury Following Acute Ischemic Stroke
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Stroke, Ischemic
Cardiac Complication
Keywords: stroke
stroke-heart syndrome
troponin
myocardial stunning
acute coronary syndrome
periodic repolarization dynamics
cardiac complications
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2019-03-27
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: consecutive patients with acute ischemic stroke admitted to the hospital's stroke unit will be systematically screened for eligibility

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of myocardial edema without late gadolinium enhancement (native T1, T2 mapping)
timeFrame: within five days of admission to hospital
measure: Rate of myocardial fibrosis with late Gadolinium enhancement (LGE) and acute edema in CMR
timeFrame: within five days of admission to hospital
measure: Rate of signs of left ventricular dysfunction in the CMR
timeFrame: within five days of admission to hospital
measure: Rate of acute disturbance of microcirculation
timeFrame: within five days of admission to hospital
measure: Rate of impaired left ventricular function and transient impaired left ventricular function in transthoracic echocardiography
timeFrame: within seven days of admission to hospital
Secondary outcomes:
measure: Rate of pathologic Periodic Repolarization Dynamics (PRDs) and Deceleration Capacity (DC)
timeFrame: within seven days of admission to hospital
measure: Difference in specific microRNA pattern in participants with myocardial damage induced by acute ischemic stroke
timeFrame: within seven days of admission to hospital
measure: Mortality
timeFrame: at one week and twelve months after the initial event
measure: Functional outcome
timeFrame: 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
measure: Rate of cardiovascular events
timeFrame: at one week and at twelve months after the initial event
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité-Campus Benjamin Franklin
Study officials:
affiliation: Charite University, Berlin, Germany
name: Jan Scheitz, PD Dr. med.
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
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.
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.