RecruitingACTRN12621000635864

Unravelling the Mechanisms Underpinning the Broken Heart Syndrome

Takotsubo cardiomyopathy: Truly a syndrome of cardiac catecholamine excess? Understanding the effects on cardiac sympathetic nerve activity.

Sponsor

Prof Markus Schlaich

Enrollment

80 participants

Start Date

Mar 16, 2023

Study Type

Observational

Conditions

Takotsubo Syndrome

Summary

Takotsubo syndrome, also known as the broken heart syndrome, is an acute and commonly reversible heart dysfunction characterised by changes in the structure of the heart. The condition is frequently triggered by a sudden physical or emotionally stressful event. It has long been postulated that an excess of the “fight or flight” hormones adrenaline and noradrenaline (collectively called catecholamines) caused by substantial activation of the sympathetic nervous system in the heart might play a key role in the development of this syndrome. However, this has not yet been proven, and the exact mechanism of Takotsubo syndrome remains subject to debate. The research project aims to better understand the biological mechanisms that cause this syndrome. In this study, we will, for the first time, directly measure the amount of catecholamines released from the heart in affected patients and explore its association with impaired heart function characteristic of the condition. Understanding the relevant mechanisms will allow more tailored therapies to further improve the management and outcomes of patients suffering from broken heart syndrome.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria9

(1) transient regional wall motion abnormalities of LV or right ventricle myocardium which are frequently but not always preceded by a stressful trigger;
(2) the regional wall motion abnormalities usually extend beyond a single epicardial vascular distribution and often results in circumferential dysfunction of the ventricular segment
involved;
(3) the absence of culprit atherosclerotic CAD including acute plaque rupture, thrombus
formation and coronary dissection or other pathological conditions to explain the pattern of temporary LV dysfunction observed (e.g. hypertrophic cardiomyopathy, viral myocarditis);
(4) new and reversible electrocardiography (ECG) abnormalities (ST-segment elevation, ST-depression, LBBB, T-wave inversion and/or QTc prolongation) during the acute phase (less than 3 months);
(5) significantly elevated BNP or NT-proBNP during the acute phase;
(6) positive but relatively small elevation in cardiac troponin measured with a conventional assay (i.e. troponin negative levels is possible);
(7) recovery of ventricular systolic dysfunction on cardiac imaging at follow-up (after 3 months).

Exclusion Criteria2

In ~25% of patients, significant coronary artery disease will be detected and account for their symptoms. If a coronary artery stenosis is detected during coronary angiography, percutaneous coronary interventions if required, will be performed as deemed appropriate by
the treating physician and management and follow up arranged as per standard guidelines. If deemed safe by the interventional cardiologist, these patients may still undergo cardiac NA/A spillover assessment and will serve as a “control group” for those with Takotsubo Syndrome. If not, they will be excluded from the study.

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Interventions

This study aims to (1) comprehensively assess the level of cardiac sympathetic nerve activity in patients presenting with Takotsubo syndrome (TS) in the acute phase (days 1-3 after presentation) and at 3 months of follow-up; (2) to investigate whether cardiac adrenaline co-transmission plays a pathophysiologic role in TS; and (3) to evaluate the temporal changes in indices of myocardial contractility between the acute phase (days 1-3 after presentation) and at 3-month follow-up. All patients will undergo the following assessments at these time points: Pathology (cardiac enzymes, full blood count, blood glucose, kidney function & hormone profile): Baseline and 6 months. Electrocardiogram: Baseline and 6 months Transthoracic echocardiography: Baseline and 6 months Coronary angiography and ventriculography: Baseline Cardiac catheterisation: Within 1-3 days of presentation 18-FDG-PET/CT scan: Baseline and 6 months Cardiac MRI: Within 1-3 days of presentation Microneurography: Within 1-3 days of presentation and 6 months Quality of Life Questionnaires: Baseline and 6 months.