Clinical trial NCT04074122: Electromechanical Profiling of the Long-QT Syndrome (LQTS)
Official title: Electromechanical Profiling of Arrhythmogenic Substrates and Triggers in the Long-QT Syndrome
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Long QT Syndrome
Sudden Cardiac Death
Ventricular Tachycardia
Keywords: Electromechanical Mapping
Risk Stratification
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: University of Freiburg
name: University of Bern
First posted: 2019-08-29
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Potential study subjects will be selected from the Cardiogenetic or Cardiac Outpatient Clinic or during their in-hospital stay.

Brief summary: High-resolution, non-invasive electromechanical mapping in genotyped long-QT syndrome patients and healthy controls at baseline and during smart provocation.

Detailed description: Using simultaneous ECG-imaging, speckle-tracking analysis and tissue-phase mapping with MRI we will assess electromechanical dispersion at rest. Regional electromechanical elasticity will be investigated during adenosine and epinephrine, isoprenaline infusions and is postulated to increase sudden cardiac death risk prediction in the individual patient.

Eligibility criteria: 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.
* 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.

Primary outcomes:
measure: Differences in regional electromechanical dispersion between LQTS patients and controls
timeFrame: At day of investigation
measure: Differences in regional electromechanical dispersion between symptomatic and asymptomatic LQTS patients
timeFrame: At day of investigation
Secondary outcomes:
measure: Correlation of electromechanical dispersion between LQTS type 1, 2, and 3.
timeFrame: At day of investigation
measure: Relation between global electromechanical window vs regional electromechanical dispersion in LQTS
timeFrame: At day of investigation
measure: Correlation between mechanical dispersion using TPM-MRI and cine-MRI
timeFrame: At day of investigation
measure: Correlation between mechanical dispersion using TPM-MRI and speckle-tracking echocardiography
timeFrame: At day of investigation
Other outcomes:
Locations:
Study officials:
affiliation: Maastricht UMC+
name: Paul Volders, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Haugaa KH, Edvardsen T, Leren TP, Gran JM, Smiseth OA, Amlie JP. Left ventricular mechanical dispersion by tissue Doppler imaging: a novel approach for identifying high-risk individuals with long QT syndrome. Eur Heart J. 2009 Feb;30(3):330-7. doi: 10.1093/eurheartj/ehn466. Epub 2008 Oct 21.
citation: Haugaa KH, Amlie JP, Berge KE, Leren TP, Smiseth OA, Edvardsen T. Transmural differences in myocardial contraction in long-QT syndrome: mechanical consequences of ion channel dysfunction. Circulation. 2010 Oct 5;122(14):1355-63. doi: 10.1161/CIRCULATIONAHA.110.960377. Epub 2010 Sep 20.
citation: ter Bekke RM, Volders PG. Arrhythmogenic mechano-electric heterogeneity in the long-QT syndrome. Prog Biophys Mol Biol. 2012 Oct-Nov;110(2-3):347-58. doi: 10.1016/j.pbiomolbio.2012.07.007. Epub 2012 Jul 24.
citation: ter Bekke RM, Haugaa KH, van den Wijngaard A, Bos JM, Ackerman MJ, Edvardsen T, Volders PG. Electromechanical window negativity in genotyped long-QT syndrome patients: relation to arrhythmia risk. Eur Heart J. 2015 Jan 14;36(3):179-86. doi: 10.1093/eurheartj/ehu370. Epub 2014 Sep 8.
citation: Shimizu W, Antzelevitch C. Differential effects of beta-adrenergic agonists and antagonists in LQT1, LQT2 and LQT3 models of the long QT syndrome. J Am Coll Cardiol. 2000 Mar 1;35(3):778-86. doi: 10.1016/s0735-1097(99)00582-3.
citation: Viskin S, Rosso R, Rogowski O, Belhassen B, Levitas A, Wagshal A, Katz A, Fourey D, Zeltser D, Oliva A, Pollevick GD, Antzelevitch C, Rozovski U. Provocation of sudden heart rate oscillation with adenosine exposes abnormal QT responses in patients with long QT syndrome: a bedside test for diagnosing long QT syndrome. Eur Heart J. 2006 Feb;27(4):469-75. doi: 10.1093/eurheartj/ehi460. Epub 2005 Aug 16.