The Inherited Heart Rhythm Disease Clinic at Hotel Dieu Hospital

Canadian Genetic Heart Rhythm Network Provides Coordinated Approach to the Investigation of Inherited Heart Rhythm Disorders Investigating inherited cardiac rhythm diseases is the focus of an innovative new clinic at Hotel Dieu Hospital. The Inherited Heart Rhythm Disease Clinic is one of the few places in Canada that offers genetic testing for arrhythmia patients and their families. Read more about this unique clinic here. The Inherited Heart Rhythm Disease Clinic specializes in genetic testing of heart rhythm diseases for patients and their families. They test specifically for sudden arrhythmia death syndromes (SADS), which often go undetected because patient symptoms are commonly misdiagnosed or left untreated. Diseases in the SADS category include long QT syndrome (LQTS), short QT syndrome, hypertrophic cardiomyopathy (HCM), Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy (ARVC), catecholaminergic polymorphic ventricular tachycardia (CPVT) and others. In particular, LQTS has been implicated as the cause in up to 10 percent of sudden infant death syndrome (SIDS) cases. Other conditions are suspected as the cause of unexpected drowning in good swimmers. “These conditions are relatively rare, but we feel they go undiagnosed or under-diagnosed most of the time,” says Dr. Chris Simpson, medical director of the joint cardiac program at Hotel Dieu and Kingston General Hospital — both academic teaching hospitals — and chief of cardiology at Queen’s University in Kingston. He continues, “Deaths of young people may be put down to ‘natural causes’ or ‘unexplained’ because often there is nothing to see at autopsy. The defect, however, is at the molecular level. These diseases are especially tragic because they occur in young, otherwise healthy people, and because they can strike whole extended families.” The Inherited Heart Rhythm Disease Clinic will specialize in patients and their families at risk of cardiac arrhythmia by bringing together a multidisciplinary team comprised of electrophysiologists, a pediatric cardiologist, a social worker, geneticists and genetics counselors all in one setting. “It provides whole-family care and support,” says Dr. Simpson. “We have access to world-class procedures and testing, including electrophysiology testing and advanced mapping, genetic testing and other leading-edge procedures.” The clinic is also distinguished as one of the founding members of the Canadian Genetic Heart Rhythm (CGHR) Network, a federation of 14 clinics nationwide that represents a collaboration among Canadian heart rhythm specialists with an interest in inherited heart rhythm disorders. “The network is an excellent tool for tracking and coordinating medical information about patients and families, who may be spread out across the country,” says Dr. Simpson. “We also share clinical protocols and collaborate on education and research. It’s a united effort to improve recognition and treatment of these conditions that has already led to several publications in high-impact journals.” In addition, the CGHR Network provides heart rhythm specialists with organizational and political clout. For example, it spearheaded a successful effort a year ago to persuade the Chief Coroner of Ontario (population 11,000,000) to agree to the collection of tissue from anyone under age 35 who died unexpectedly. The tissue is saved at minus 20 degrees Celsius to allow for extraction of DNA for genetic analysis, which makes it easier to subsequently screen surviving family members. “Before, those deaths would have been ‘by natural causes’,” says Simpson. “But now we have a province-wide systematic means to examine these deaths via molecular autopsy.” Currently, the Inherited Heart Rhythm Disease Clinic at Hotel Dieu is following well over 100 patients. The youngest is 6 months old, while the oldest are in their 80s. However, by far, the clinic focuses on teens and young adults in their 20s. Dr. Simpson and his team adopt what he calls a ‘CSI-style approach’ to its clinical investigations. He posits the example of a 17-year-old female patient whose mother died suddenly at a relatively young age. Working backwards, the team would first try to locate the mother’s autopsy report and tissue that would be sent for genetic analysis. “We would then look at our patient and her family to establish a genetic history or pedigree to determine who else might potentially be at risk,” explains Dr. Simpson. “We would set about to find the underlying condition through specialized testing. That would include low and high-tech interventions — everything from drug infusions that provoke electrocardiogram changes characteristic of certain diseases to highly sophisticated DNA analysis.” “Genetic testing is relatively new and is improving all the time. We don’t yet know all of the genes that cause these diseases, but more and more we’re able to identify a gene mutation in an individual patient. That makes screening of the family much easier since we can then look for that particular gene mutation in everyone,” says Dr. Simpson. The value of the ‘CSI approach’ in diagnosing patients at risk for inherited heart rhythm disease was the subject of a research paper (“CASPER: Study Design and Preliminary Results in Probands from the Cardiac Arrest Survivors with Preserved Ejection Fraction Registry”) published in July 2009 in Circulation, the journal of the American Heart Association. Co-authored by Dr. Simpson and his CGHR colleagues, including lead author Dr. Andrew Krahn from the University of Western Ontario, the multi-center study was designed to evaluate the results of systematic assessment of patients and their relatives who have a history of unexplained cardiac arrest that may be caused by uncommon genetic conditions, including primary electrical disease and latent cardiomyopathy. The study demonstrated that a systemic approach helps to diagnose primary electrical diseases as well as latent structural causes of cardiac arrest. “There’s very little seam between clinical care and research in the CGHR Network,” says Dr. Simpson. “The CASPER study proved that doing intensive investigative work — diving into family history, looking for very subtle changes on an electrocardiogram, exploring every angle possible in a systematic way — can help us to make extremely difficult diagnoses. It boils down to doing the right things at the right time in a coordinated, specialized way. “When we apply our investigative tests in a systematic way, we arrive at a diagnosis in more than 50 percent of those previously undiagnosed cases. That has significant implications for generations of extended families spawning out from the original person who had cardiac arrest — there is a multiplicative effect.” Along with supporting pioneering research into ways of testing for SADS, the Inherited Heart Rhythm Disease Clinic is also participating in Queen’s University research that targets the disruptions in the flow of chemicals through the cellular wall. Understanding abnormalities in these channels, says Simpson, could help to explain electrical problems in the heart that result in sudden cardiac arrest. Simpson says that such research is essential in the rapidly moving field of SADS. “Our patients understand that we only know what we do about these diseases because of research. They’re usually very generous with their time in helping us with that research mission.” For patients, the good news is that SADS are treatable. Some individuals respond well to medications such as beta blockers, while others may require an implantable cardioverter defibrillator (ICD) or catheter ablation. So far, the clinic has treated about 90 percent of its patient with medication, while 10 percent have required either implants or catheter ablation. Equally important, however, is patient and family education on a subject that can lead variously to feelings of anxiety, fear and guilt. Cardiologist and team member Dr. Damian Redfearn describes the clinic’s methodology as a combination of high-tech medicine and social science. “Amongst many other reasons, the clinic is unique for the family and privacy implications of SADS, hence the great need for education, counseling and planning,” explains Dr. Redfearn. “These diseases call for some lifestyle changes, and there are many emotions involved. Parents may feel guilty about passing a ‘defective’ gene to their kids, for example, or young athletes may feel they’ll be cut off from sports. The key is education — understanding what can be done and what might have to be avoided. For instance, some people may need to avoid the commonly prescribed antibiotic erythromycin because it could make them more vulnerable to SADS.” “The management of these conditions isn’t uniform. We take each case on an individual basis because each person’s risk is slightly different. That’s why the multi-disciplinary strategy is so important. It lets us come at each patient in a targeted way and on different levels. It’s a very patient-centered approach.” And that approach is showing results, says Dr. Simpson. “There’s no question that we’ve picked up cases in families that would not have been detected otherwise, and we’ve treated them successfully. And, thanks to the national CGHR Network, we have a high level of coordination across the country that makes it easier to share pedigrees and do the necessary genetic testing. We’re working hard to ensure that everyone in a family who needs to be screened is screened.” “This is fascinating work. It’s like nothing else we do.” For more information, please visit: https://www.hoteldieu.com/ https://www.heartrhythmresearch.ca https://www.chrsonline.ca/