Diagnostic Test for CRDS

(DIAGNOSE CRDS Trial)

Recruiting at 25 trial locations

Overseen By Jason Roberts, MD MAS

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Population Health Research Institute

Must not be taking: Qt prolonging, Class I/III anti-arrhythmics

Disqualifiers: Ventricular cardiomyopathy, Long QT, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to discover a new method for diagnosing Calcium Release Deficiency Syndrome (CRDS), a condition that can increase the risk of sudden heart problems. Researchers are testing whether a special heart pacing method (also known as cardiac pacing or artificial pacing) can identify CRDS without complex lab tests. The trial includes various groups, such as individuals with known CRDS, a heart condition called CPVT, unexplained past heart arrests, and others undergoing heart studies. Suitable candidates for this trial may have specific heart conditions or experiences, like past unexplained heart problems, and must be able to provide informed consent. As an unphased trial, this study offers participants the opportunity to contribute to groundbreaking research that could simplify CRDS diagnosis.

Will I have to stop taking my current medications?

If you are taking a QT prolonging medication or certain anti-arrhythmic drugs, you may need to stop them before participating in the trial, especially during specific procedures. The protocol does not specify a washout period, but you should discuss your current medications with the trial team.

What prior data suggests that this diagnostic method is safe for diagnosing CRDS?

Research has shown that pacing, a method to control the heart's rhythm, is generally well-tolerated by patients. Studies on cardiac pacing indicate that it can improve heart function and is often used for heart rhythm issues. For instance, pacing is commonly used in people with severe heart block, a condition where the heart beats too slowly, and it has improved symptoms and outcomes.

Pacing is not a new treatment. Doctors have used it for a long time, and most patients do well with it. Serious side effects are rare. Some people might feel minor discomfort or irritation where the pacing device is placed, but these issues are usually manageable.

For those considering joining a trial involving pacing, this background suggests it is likely to be safe based on current evidence. However, discussing any concerns with a healthcare provider is always best. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new diagnostic approach for Cardiac Repolarization Disorders (CRDS) using pacing. Unlike traditional methods that primarily focus on standard electrocardiograms or medication adjustments, this technique involves administering separate ventricular and atrial pacing trains. By evaluating the ventricular repolarization response after pacing, researchers aim to gain deeper insights into the heart's electrical activity. This could potentially lead to more accurate diagnoses and personalized treatments for those with CRDS, addressing specific electrical abnormalities directly.

What evidence suggests that cardiac pacing is effective for diagnosing CRDS?

Research has shown that cardiac pacing, the treatment method under study in this trial, can help diagnose electrical problems in the heart. Studies have found that non-invasive cardiac mapping, which uses pacing, helps pinpoint the sources of heart rhythm issues. This method already treats various heart conditions in medical practice. Temporary cardiac pacing has also helped with heart rhythm problems after surgery. These findings suggest that pacing can be a useful tool in diagnosing and understanding conditions like Calcium Release Deficiency Syndrome (CRDS). ^{1 5 6 7 8}

Who Is on the Research Team?

Ziv Dadon, MD

Principal Investigator

Shaare Zedek Medical Center

Jason D Roberts, MD MAS

Principal Investigator

McMaster University

Wayne Chen, PhD

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

This trial is for individuals suspected to have Calcium Release Deficiency Syndrome (CRDS), a genetic heart rhythm disorder that can lead to sudden cardiac death. Participants should be able to undergo a diagnostic test involving brief, controlled increases in heart rate.

Inclusion Criteria

I have a genetic mutation in RyR2 or CASQ2 that affects my heart.

I had a cardiac arrest that remains unexplained even after several heart tests.

I am scheduled for a detailed heart rhythm test.

Exclusion Criteria

I am unable to understand and agree to the study's details on my own.

I am taking medication that affects my heart's rhythm, except for flecainide.

I am currently taking medication that affects my heart's rhythm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pacing

Separate ventricular and atrial pacing trains are administered at different cycle lengths to evaluate the ventricular repolarization response

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the pacing procedure

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pacing

Trial Overview

The study aims to evaluate if CRDS can be diagnosed without cellular tests by observing the heart's electrical recovery after it is briefly sped up using a method called pacing. This could simplify and speed up diagnosis.

How Is the Trial Designed?

Group I: Pacing Experimental Treatment 1 Intervention

Separate ventricular and atrial pacing trains will be administered at different cycle lengths and the ventricular repolarization response on the first sinus beat following the subsequent pause will be evaluated.

Who Is Running the Clinical Trial?

Population Health Research Institute

Lead Sponsor

Trials

165

Recruited

717,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

The use of a steel wire loop electrode for emergency transthoracic cardiac pacing was successful in capturing heart activity in most patients, with 8 out of 13 cases of cardiac arrest showing effective pacing, especially when performed quickly after arrest.

This method proved to be safe and reliable, particularly when conventional pacing methods failed, suggesting it could significantly improve resuscitation outcomes in critical situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The clinical application of the emergency remedial transthoracic cardiac pacing used by a steel wire loop electrode]. Ma, J., Su, L., Qiu, J., et al.[2019]

In a study of 22 patients undergoing coronary angiography, atrial pacing induced more positive ECG results for ischemia compared to standard exercise testing, with 94% of patients with significant coronary artery disease (CAD) showing ischemic changes during pacing.

The concordance rate of ECG changes between exercise and pacing tests was high at 90%, suggesting that atrial pacing could be a reliable alternative for detecting CAD, especially given its higher sensitivity in identifying ischemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pacing stress test: a reexamination of the relation between coronary artery disease and pacing-induced electrocardiographic changes. Heller, GV., Aroesty, JM., McKay, RG., et al.[2019]

Artificial pacemakers are crucial for patients with inadequate intrinsic heart rates, as they provide necessary electrical impulses to maintain a normal cardiac rhythm.

Recent advancements in pacemaker technology have made it essential for physicians to understand their use and the potential complications that may arise with these devices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Artificial cardiac pacemakers. Das, G., Carlblom, D.[2018]

The novel pacing guidewire demonstrated strong accuracy in measuring pacing thresholds and R-wave sensing during cardiac resynchronization therapy (CRT) procedures, particularly at basal and middle left ventricular sites, with significant correlations to LV lead measurements (r values up to 0.930).

The guidewire can effectively predict the presence of phrenic nerve stimulation at high pacing outputs with an 87% concordance rate, indicating its potential utility in optimizing CRT implantation sites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of a novel pacing guidewire in pre-implantation testing at different left ventricular sites in cardiac resynchronization therapy procedures. Chan, NY., Choy, CC., Lau, CL., et al.[2021]

Diagnostic pacing, particularly rapid atrial pacing, is an effective method for stressing the heart in patients with ischemic heart disease, helping to provoke symptoms and assess heart function.

This technique has been valuable in evaluating the effectiveness of treatments for angina and in understanding the mechanisms of heart rhythm disorders, including re-entry supraventricular tachycardias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic uses of electrical pacing. Zir, LM., DeSanctis, RW., Harthorne, JW.[2008]

Modern pacemakers have advanced features that not only help manage arrhythmias but also meet the physiological needs of patients, including dual-chamber pacing and cardiac resynchronization therapy, which can significantly reduce the incidence of atrial fibrillation.

While modern pacemakers show acceptable performance and safety, the reduction in all-cause mortality due to physiological pacing has not yet been proven in randomized trials, indicating that further research is needed to confirm their long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modern pacemakers: hope or hype? DAS, MK., Dandamudi, G., Steiner, HA.[2009]

In a study of 26 patients with implanted pacemakers, non-invasive programmed ventricular stimulation successfully induced complex ventricular arrhythmias in 42% of cases, allowing for tailored treatment options based on the type of arrhythmia observed.

This method is a safe and repeatable alternative for assessing cardiac stability without the need for fluoroscopy, although it has limitations such as not being able to pace from the right ventricle outflow tract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Electric programmed ventricular stimulation using a permanent cardiac pacing system--a noninvasive method in arrhythmia]. Novotný, T., Dvorák, R., Lábrová, R., et al.[2009]

In a study of 151 patients who received complex cardiac devices (ICD, CRT-P, CRT-D) over two years, the overall procedural success rate was an impressive 99.3%, indicating high efficacy in implantation.

Complications occurred in 9.3% of cases, with lead displacement being the most common issue (5.3%), but there were no procedure-related deaths, highlighting the safety of these procedures when performed by experienced clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complex cardiac pacing in the setting of a district general hospital: procedural success and complications. Rahbi, H., El-Din, M., Salloum, M., et al.[2020]

Electrophysiologic testing, which involves placing electrode catheters in the heart to record electrical activity, is crucial for diagnosing arrhythmias and assessing treatment options in patients with various heart rhythm disorders.

This testing is particularly beneficial for patients with conditions like sinus node dysfunction, ventricular tachycardia, and those who have experienced cardiac arrest, as it helps evaluate the effectiveness of therapies such as antiarrhythmic drugs and procedures like transcatheter ablation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical intracardiac electrophysiologic testing: technique, diagnostic indications, and therapeutic uses. Hammill, SC., Sugrue, DD., Gersh, BJ., et al.[2019]

Atrial pacing is a safe and effective method for assessing patients with angina pectoris, providing valuable information for clinical decision-making.

This technique is particularly useful for patients with uncertain diagnoses of angina or those being evaluated for potential surgical interventions for ischemic heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of atrial pacing test in angina pectoris. Balcon, R., Maloy, WC., Sowton, E.[2019]

In a study of 17 patients with an average age of 67, the 'Crown of Thorns' electrode demonstrated successful long-term physiological pacing in 16 patients over a follow-up period of 4-13 months, indicating its efficacy and reliability.

The study found that while there were some initial failures with specific generators, switching to a more sensitive unit led to successful pacing, suggesting that the electrode can be effectively used with various dual chamber generators.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of a single-pass implantable electrode for all modes of pacing. The "Crown of Thorns" lead. Wainwright, R., Crick, J., Sowton, E.[2019]

A study of 287 children with congenital heart defects showed that cardiac pacing is generally effective in the long term, with a median follow-up of 5 years, but endocardial systems had significantly better outcomes compared to epicardial systems.

Younger age at the time of implantation was associated with a higher risk of complications and system failure, highlighting the importance of careful patient selection for cardiac pacing in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac pacing in paediatric patients with congenital heart defects: transvenous or epicardial? Silvetti, MS., Drago, F., Di Carlo, D., et al.[2013]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8674736/

Advances in Cardiac Pacing: Arrhythmia Prediction ...

Non-invasive cardiac mapping is now extensively used in clinical practice (Dubois et al., 2015) to identify the sources of electrical disorders and guide ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12130153/

Temporary Pacing for Electric Cardiac Stimulation and ...

Temporary neuromodulation can serve as an alternative to traditional temporary pacing for the treatment of postoperative cardiac abnormalities.

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1547527123023329

Significance of effective cardiac resynchronization therapy ...

Ueda et al. Clinical impact of left ventricular paced conduction disturbance in cardiac resynchronization therapy. Heart Rhythm. (2020).

4.

jacc.org

jacc.org/doi/10.1016/j.jacep.2023.06.005

Cardiac Conduction System Pacing: A Comprehensive ...

They recruited patients with LV impairment and a range of different ventricular conduction abnormalities. They found that the HOT-CRT pacing configuration ...

5.

ahajournals.org

ahajournals.org/doi/10.1161/circep.108.764621

Cardiac Pacing | Circulation: Arrhythmia and ...

But this coldness of the body was overcome within seven hours, nor did it return any more, though the disorder often returned; but the slowness of the pulse ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6702597/

Update in Cardiac Pacing - PMC - PubMed Central - NIH

Multisite and multipoint pacing represent efforts in the field of cardiac resynchronisation therapy to improve cardiac efficiency and improve clinical outcomes.

7.

heartrhythmjournal.com

heartrhythmjournal.com/article/S1547-5271(23)02026-X/fulltext

2023 HRS/APHRS/LAHRS guideline on cardiac ...

In selected patients with congenital heart disease or congenital atrioventricular block, CRT or conduction system area pacing may be considered.

8.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0022073621000789

Effects of permanent cardiac pacing on ventricular ...

Our results demonstrate that CNA reduces QTc levels through neuromodulation effect whereas CP has no effect on ventricular repolarization in patients with VVS.