Clinical Research Directory

Fetal Electrophysiologic Abnormalities in High-Risk Pregnancies Associated With Fetal Demise

Each year world-wide, 2.5 million fetuses die unexpectedly in the last half of pregnancy, 25,000 in the United States, making fetal demise ten-times more common than Sudden Infant Death Syndrome. This study will apply a novel type of non-invasive monitoring, called fetal magnetocardiography (fMCG) used thus far to successfully evaluate fetal arrhythmias, in order to discover potential hidden electrophysiologic abnormalities that could lead to fetal demise in five high-risk pregnancy conditions associated with fetal demise.

National Network for Cardiovascular Genomics: Advancing Cardiovascular Healthcare for Hereditary Diseases in Brazil's Unified Health System Through a Multicenter Registry

The goal of this observational study is to develop a registry of Brazilian patients with hereditary cardiovascular diseases, combining clinical and genomic data. The main questions it aims to answer are: Which genes are most commonly affected? What is the frequency of these genetic alterations in our population? Participants will be interviewed in routine medical care visits and their DNA will be sequenced.

Continuous Versus Intermittent cARdiac Electrical moNitorinG

The purpose of this study is to validate the continuous patch monitoring system to evaluate cardiac arrhythmias in patients receiving drugs that can cause cardiac complications and compare the continuous patch system with standard electrocardiograms (ECGs).

Frequency of Hypoglycemia in Children With Beta-blocker Treated Long QT-syndrome

The goal of this observational study is to investigate the frequency and characteristics of hypoglycemic episodes in children with long QT syndrome (LQTS) and beta-blocker treatment, specifically those receiving propranolol, compared to healthy controls. The study focuses on children under seven years with genetically confirmed LQTS and beta-blocker therapy, as well as healthy siblings as controls. The main questions it aims to answer are: * Does hypoglycemic episodes occur in children with LQTS who are treated with propranolol? * Are there asymptomatic episodes of low blood glucose that could affect well-being and neurological development? * Are there individual differences in susceptibility to hypoglycemia, and do genetic factors explain these differences? * What is the incidence of hypoglycemia leading to emergency visits or hospitalizations among LQTS patients compared to healthy controls? Researchers will compare children with LQTS on propranolol to healthy siblings to see if the frequency and severity of hypoglycemia differs between groups. Participants will: Have a Dexcom G7 continuous glucose monitor installed to record glucose profiles for ten days, both during an healthy episode and during an infection (when risk for hypoglycemia is increased). If differences in susceptibility to hypoglycemia are observed, genetic data from the Helsinki biopank will be analyzed to explore potential genetic factors underlying these differences. Visits to emergency clinic and hospitalizations due to hypoglycemia will be retrospectively reviewed for all LQTS patients under 16 years old and compared to healthy controls. Additional Details: The study is conducted at Helsinki University Hospital (HUH) Children and Adolescents and the New Children's Hospital clinical research unit. The study aims to recruit 20-40 LQTS patients and 10 healthy controls. The study is ethically justified, with no extra laboratory tests or costs for participants, and written consent will be obtained from parents and capable children. The results are expected to improve the safety of propranolol treatment in LQTS children by identifying risk factors for hypoglycemia and informing preventive strategies, such as dietary guidance, use of glucose monitoring devices during illness, or considering selective beta-blockers for high-risk patients.

Evaluation of Exercise Testing and Physical Activity in Children and Adolescents Living With Inherited Arrhythmias

The goal of this observational study is to evaluate exercise testing and daily physical activity in children and adolescents who are diagnosed with an inherited arrhythmia. The main question it aims to answer is: Does maximum heart rate during controlled exercise tolerance testing accurately reflect maximum heart rate and peak exercise levels during free living daily physical activity in children and adolescents diagnosed with an inherited arrhythmia? Participants will: * Complete routine exercise tolerance testing * Record daily physical activity and exercise over two weeks, while wearing an activity and heart rate monitor and digit diary. * Complete a physical activity questionnaire at the end of two weeks.

Building of a Diagnostic/Prognostic Database for Human ERG Variant Effects

Cardiac channelopathies induce severe heart rhythm or conduction disorders. Mutations of the KCNH2 gene, that encodes the human (h) ERG channel, is responsible for 30-40% of all cases of long QT syndrome (inherited LQT2). Besides, hERG is frequently responsible for off-target effects of several pharmacological agents (acquired LQT2). With the advent of Next Generation Sequencing, hundreds of new KCNH2 variants are accumulating in regional databases including those developed by french centers of references. Worldwide, we estimate there are more than 1000 variants for hERG channel. Unfortunately, many of these new variants appear to be of unknown functional significance in spite of available clinical and genetic information. Little is known on whether they affect the channel biophysical properties, its expression at the cell surface and/or its structure. Yet, this information is crucial to determine the real degree of pathogenicity of these variants, and therefore to make the proper diagnosis on inherited LQT2, counsel the patient for his treatment and improve the management of the patient's life. Our ambition is therefore to tackle this issue of variant significance by (i) launching a large-scale multi-functional evaluation of hERG variants, (ii) introducing for the first time a formatted large-scale pathogenicity annotation score for all variants that have been functionally evaluated by this multi-parametric approach, and (iii) regrouping all the relevant information collected in every French Regional centers of reference into a single National database hosted by an infrastructure that possesses enough flexibility for continuous data implementation and cross-referencing. The database will integrate the latest International guidelines for functional pathogenicity annotation. This project will also include the pharmacological characterization of several drugs susceptible to produce acquired LQT2 with variable severities. We aim to understand whether there are structural regions within hERG channel in which the introduction of a variant is more prone to increase the risk of acquired LQT2 or if, on the contrary, a set of variants may relatively protect some patients against LQT2-inducing drugs.

Wearable Devices for Patient Monitoring in Long QT Syndrome

The main research question of this study is whether wearable devices have utility in monitoring patients with Long QT syndrome.

Comparing Direct vs Indirect Methods for Cascade Screening

An important aspect of successful genomic medicine implementation is developing effective approaches for screening at-risk family members after probands are identified, also known as cascade screening. Most cascade screening studies conducted to date have been conducted outside the US, and very few studies have used a rigorous approach involving a comparator group or randomized controlled design. A major question in the field is how to most effectively implement cascade screening, given commonly cited communication barriers, while respecting privacy among probands and family members. This study will conduct a randomized controlled trial to assess direct contact of relatives by study team members vs indirect, or proband-initiated, contact. We will assess efficacy of the cascade screening intervention, patient-centered outcomes regarding mental, physical, and psychosocial outcomes in probands and family members, and implementation evaluation outcomes. Individuals who are known to carry the KCNQ1 Met224Thr or APOB Arg3527Gln variant will be eligible to participate. After providing consent and being deemed eligible, individuals will be randomized in a 1:1 manner into the direct or indirect contact of family members arm of the study. The randomization will be stratified by variant to ensure equal representation of each variant in the study arms. Individuals in the indirect arm will be instructed to contact their first-degree family members about the opportunity to be screened. They will be provided with a disease-specific pamphlet and a family letter explaining the cascade screening. In the direct arm, probands will be advised that the study staff will be contacting their family members. They will be instructed to also contact their family members prior to the study team contacting them. Approximately two weeks after this meeting with the proband, the study staff will mail letters to eligible first-degree family members of the probands. If we do not hear back from individual family members, we will follow-up with another letter, telephone call, or home visit. The information contained in the letters will be the same information for both the direct and indirect arms of the study. All interested family members will receive pre-test counseling and free, in-home, saliva-based genetic testing, and post-test counseling.

Clinical Cohort Study - TRUST

The "Long-term Outcome and Predictors for Recurrence after Medical and Interventional Treatment of Arrhythmias at the University Heart Center Hamburg" (TRUST) study is an investor-initiated, single-center, prospective clinical cohort study including patients treated with cardiac arrhythmias or at high risk for cardiac arrhythmias. The design enables prospective, low-threshold, near complete inclusion of patients with arrhythmias treated at the UHZ. Collection of routine follow-up data, detailed procedural information and systematic biobanking will enable precise and robust phenotyping.