Beta-blockers, Echocardiography, Left Ventricular Function, Takotsubo Cardiomyopathy
Conditions
Keywords
Takotsubo Cardiomyopathy, beta-blockers, echocardiography, left ventricular function, acute myocardial infarction, acute coronary syndrome, coronary angiography, Normal coronary arteries, Heart failure, stress
Brief summary
The Beta-blockers in Takotsubo syndrome (TTS) (β-Tako) trial, is an academic, pragmatic, prospective, multicenter randomized clinical trial, aiming to assess the efficacy of beta-blockers (BB) in TTS patients. Two-hundred patients with TTS will be randomized (1:1) to BB (n=100) or no BB (n=100). BB with alpha or nitric oxide release activity will be used in the treatment arm. The primary endpoint will be the comparison of the wall motion score index by echocardiography at 7 days. A composite clinical endpoint (death, stroke, admission for recurrent TTS, ACS, heart failure or atrial fibrillation) at 1 year, will be assessed by an independent clinical events committee. Several sub-studies will be performed. The β-Tako trial will inform treatment decisions in this uniquely challenging clinical entity.
Detailed description
Takotsubo syndrome (TTS) is a cardiac condition mimicking acute coronary syndrome (ACS), characterized by transient left ventricular (LV) dysfunction in the presence of normal coronary arteries. Its etiology remains unknown but reversible microvascular dysfunction secondary to an adrenergic surge appears implicated. Treatment is empiric although in clinical practice most patients receive beta-blockers (BB). The Beta-blockers in TTS (β-Tako) trial, is an academic, pragmatic, prospective, multicenter randomized clinical trial, aiming to assess the efficacy of BB in TTS patients. TTS diagnosis will be confirmed by invasive coronary angiography and serial echocardiographic studies. Two-hundred patients with TTS will be randomized (1:1) to BB (n=100) or no BB (n=100). BB with alpha or nitric oxide release activity will be used in the treatment arm. The primary endpoint will be the comparison of the wall motion score index by echocardiography at 7 days, analyzed in an independent corelab. Changes in LV ejection fraction and global longitudinal strain will be also evaluated. A composite clinical endpoint (death, stroke, admission for recurrent TTS, ACS, heart failure or atrial fibrillation) at 1 year, will be assessed by an independent clinical events committee. Several sub-studies (clinical, imaging, biomarkers, pharmacogenetic, mRNAs, quality of life) will be performed. The β-Tako trial will generate valuable scientific evidence to address unmet clinical needs and inform clinical and treatment decisions in this uniquely challenging clinical entity.
Interventions
DRUGBeta blocker
Pragmatic design. Any beta-blocker with alpha or NO activity may be used
Sponsors
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Spanish Society of Cardiology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Outcome assessors blinded to treatment allocation Blinded independent clinical event committee PROBE initiative
Intervention model description
Randomized trial with 2 arms
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent. * Diagnosis of TTS with exclusion of significant coronary artery disease (CAD) by invasive coronary angiography
Exclusion criteria
* Patients diagnosed of TTS \> 48 hours before. * Persistent ccardiogenic shock or severe hemodynamic instability * Persistent severe (\>30 mmHg) intraventricular gradient * Previous diagnosis of severe valvular or ventricular disease or prior myocardial infarction secondary to atherosclerotic CAD * Patients already receiving treatment with betablockers (\*) * Absolute contraindication/indication for beta-blockers (\*\*) * Poor echocardiographic window * Pregnant or breastfeeding women. * Participation in another clinical trial. (\*) Betablockers at a therapeutic dose at the time of symptom´s onset. (\*\*) Close ECG monitoring required in patients with hypotension, bradycardia or cQT interval prolongation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Wall motion score index | 7 days | Wall motion score index by echocardiography to assess recovery of left ventricular function Wall motion score index (WMSI) ranges from 1 to 4 (1 is normal and 4 worse) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Global longitudinal strain | 7 days | Global longitudinal strain by echocardiography to assess recovery of left ventricular function |
| Left ventricular ejection fraction | 7 days | Left ventricular ejection fraction by echocardiography to assess recovery of left ventricular function |
| Delta (Change) in: wall motion score index, left ventricular ejection fraction, global longitudinal strain | 7 days | Changes in LV function by imaging |
| Combined clinical endpoint (death, stroke, recurrent TTS, heart failure, acute coronary syndrome, atrial fibrillation | 1 year | Combined clinical endpoint |
| Individual endpoints of the combined clinical endpoint Occurrence of death, stroke, recurrent TT, heart failure, acute coronary syndrome, atrial fibrillation will be analyzed and compared individually | 1 year | Individual clinical endpoints Occurrence of death, stroke, recurrent TT, heart failure, acute coronary syndrome, atrial fibrillation will be analyzed and compared individually in the 2 groups |
| Angina and quality of life status during daily life assessed in routine clinical practice | 1 year | Evaluated in clinical visits |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pharmacogenetic substudy | 1 year | To assess pharmacogenetic implications of different beta-blockers used The pharcacogenetics of the 2 different betablockers used in this study will be studied in relation to the main echocardiographic and clinical endpoints |
| Coronary angiography | 1 year | To assess correlation with angiographic features and clinical findings and prognosis |
| Biomarkers, inflammatory data, mRNAs | 1 year | Association with clinical findings and prognosis |
| ECG | 1 year | Correlation of ECG findings with clinical features and prognosis Different ECG parameters will be correlated with the echocardiographic and clinical outcome measures to detect potential correlations |
| Cardiac Magnetic Resonance (CMR) | 1 year | CMR to detect edema, late gadolinium enhancement to correlate with clinical data and prognosis |
Countries
Spain
Contacts
Primary ContactFernando Alfonso, MD
Outcome results
None listed