To identify arrhythmogenic electromechanical risk profiles in LQTS patients; in baseline conditions and during provocation; the recognition of risk profiles will improve risk stratification for sudden cardiac death.
ID
Source
Brief title
Condition
- Cardiac arrhythmias
- Cardiac and vascular disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Cardiac event risk prediction in LQTS patients using regional electromechanical
dispersion.
Secondary outcome
Secondary study points consist of:
• difference in electromechanical dispersion (in ms) between symptomatic and
asymptomatic genotyped LQTS patients and controls.
• comparison of electromechanical dispersion (in ms) between LQTS type 1, 2,
and 3.
• relation between global electromechanical window vs regional
electromechanical dispersion in LQTS.
• Comparison of mechanical dispersion using TPM-MRI and cine-MRI.
• Comparison of mechanical dispersion using TPM-MRI and speckle-tracking
echocardiography.
Background summary
Sudden cardiac death (SCD) imposes a large socioeconomic and psychosocial
burden, claiming almost a million deaths annually in Western societies. SCD is
mostly caused by ventricular fibrillation (VF). In young patients, inherited
arrhythmia syndromes including the long-QT syndrome (LQTS) account for 5-10% of
victims. The LQTS is traditionally considered a primary electrical disease with
prolonged repolarization, and spatial and temporal repolarization
heterogeneities. However, key publications claiming concomitant mechanical
alterations in LQTS induced a paradigm shift: Therefore, some research-field
leaders have now proposed LQTS as an electromechanical disease with
mechano-electric triggers of arrhythmia.
For the purpose of this study protocol, we hypothesize that 1) Regional
dispersion of repolarization and mechanical-strain patterns better depict the
proarrhythmic substrate than global electrical parameters; 2) The extent of
regional electromechanical heterogeneities and/or discordance of mechanical
strain determine the site of abnormal electrical impulse formation prior to
arrhythmia, whether or not through the emergence of local aftercontractions; 3)
Electromechanical profiling in patients by smart provocation with
catecholaminergic stimulation and pharmacological variation of atrioventricular
(AV) relations will improve LQTS risk stratification.
Study objective
To identify arrhythmogenic electromechanical risk profiles in LQTS patients; in
baseline conditions and during provocation; the recognition of risk profiles
will improve risk stratification for sudden cardiac death.
Study design
Multicenter, case-control study
Intervention
Pharmacological (adenosine, epinephrine) provocation, ECG-imaging and
tissue-phase mapping using magnetic resonance imaging (TPM-MRI).
Study burden and risks
LQTS patients:
Standard clinical workup: 12-lead ECG, lab tests, holter, echocardiogram and on
indication contrast-enhanced MRI.
Study related: peripheral venous access, ECG-imaging, MRI (TPM-MRI) without
contrast, pharmacological provocation.
A low dose CT scan will be performed in case of a contraindication for MRI is
present.
The incidence of arrhythmias during smart provocation are expected to be small
(<1%).
Control population:
Standard care: use of preexisting 12-lead ECG, Holter, echocardiogram and
contrast-enhanced MRI.
Study related: peripheral venous access, lab tests, 12-lead ECG, Holter,
echocardiogram, ECG-imaging, MRI (TPM-MRI) without contrast, pharmacological
provocation.
Using a one-stop-shop set-up, all clinical and study-related investigations
will be performed sequentially within two days (no need for additional hospital
visits).
Patient benefit resides in an improved risk prediction.
Outpatient visits for LQTS subjects include 12-lead ECG and Holter recording at
3, 12, and 24 months; control subjects will receive a phone call after 3
months.
P. Debyelaan 25
Maastricht 6202AZ
NL
P. Debyelaan 25
Maastricht 6202AZ
NL
Listed location countries
Age
Inclusion criteria
LQTS group (Group 1):
* Diagnosis of LQTS according to the ESC guidelines.
* Genetic testing either already performed or consent to genetic testing (at
least 5 major LQTS-related genes tested: KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2).
Control group (Group 2):
* Control subjects with structurally normal hearts.
Exclusion criteria
* Pregnancy, nursing or planning to become pregnant.
* Known allergy or strong reaction to skin electrodes or contrast agent.
* Inability to give informed consent.
* Presence of metal objects in or attached to the body.
* Dialysis.
* Cardiomyopathy (LVEF < 50%).
* Second-degree heart block or higher degrees of block.
* Sick sinus syndrome.
* Asthma.
* Chronic obstructive pulmonary disease.
* Left-main coronary artery disease.
* Unstable coronary artery disease.
* Moderate to severe valvular disease.
* Inability to undergo MRI scan (control population).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL70856.068.19 |
| Other | NL70856.068.19 |