Umeå University's logo

Background: Long QT syndrome (LQTS), Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), Brugada syndrome (BrS), and short QT syndrome are hereditary diseases caused by mutations in genes coding for cardiac ion channels. Patients carrying these mutations may be at risk of symptoms such as syncope and sudden cardiac death (SCD). To prevent symptoms, patients need to be managed properly and this management may include prophylactic medical treatment, and the use of an implantable cardioverter defibrillator (ICD) for high-risk patients. ICD treatment has previously been shown to prevent SCD, but it also carries a risk of complications and inappropriate shocks. In these studies, we investigated ICD treatment in patients with inherited arrhythmogenic channelopathies with a focus on individual risk assessment and ICD harm.

Methods: Studies I–III are observational studies that use registries to identify patients and medical records to collect data. Studies I and III are performed with a descriptive approach that focus on phenotype, genotype, and medical treatment (Study I) and the diagnostic process and treatment over time (Study III). In Study II, we use Kaplan Meier analyses and incidence rates to assess risk scores and ICD harm. Study IV is a systematic review based on a systematic search and screening process. The data, which are synthesized without meta-analysis, are from published original works.

Results: In Studies I and II, we present data on 109 Swedish LQTS patients with a first ICD implantation between 1992 and 2013 at a median age of 39 years (range, 5–78 years). Most patients received ICD treatment after aborted cardiac arrest (n=45, 41%) and after syncope despite receiving prophylactic medical treatment, i.e., beta-blockers (n=31, 29%). However, 10 patients (9%) received ICD treatment despite being asymptomatic and 17 patients (16%) after syncope without ongoing beta-blocker treatment. The incidence rate of a first appropriate shock was 4.3 per 100 person-years. Concerning ICD harm, the incidence rate of inappropriate shocks was 3.0 per 100 person-years and the corresponding rate of complications was 7.6 per 100 person-years. Using risk scores previously proposed to our cohort, we found that the patients who received appropriate shocks still had zero points (i.e., the lowest score) from the risk score.

In Study III, 39 Swedish pediatric patients had either BrS (n=7) or CPVT (n=32). Of the 32 CPVT patients, 18 (56%) had been misdiagnosed at first; however, since 2010 only two patients received an initial misdiagnosis. The treatment in CPVT patients changed over time in accordance with current guidelines.

In Study IV, the database search (4318 references) rendered a final inclusion of 40 references, including 741 children and adolescents with inherited arrhythmogenic channelopathies. Of the patients affected by ICD harm, 20% (148/741) had inappropriate shocks and 23% (145/624) had other complications. In LQTS and CPVT patients, the percentage of patients with ICD harm was lower in studies published from 2015, than before.

Conclusion: These studies illustrate both the difficulty in pre-ICD risk stratification and its important role due to high combined rates of ICD harm. ICD treatment is an important treatment option for high-risk patients with inherited arrhythmogenic channelopathies. We found improvements in how patients have been managed over time and identified the need for future research addressing benefit and harm from ICD treatment among children and adolescents.