Patient Outcomes From a Specialized Inherited Arrhythmia Clinic

The data of all patients referred to the IAC were routinely updated in the clinic’s database and were retrospectively analyzed for this study. The patients referred to the clinic are patients suspected of having an inherited cardiac disease, including LQTS, Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), short QT syndrome (SQTS), arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), and familial dilated cardiomyopathy (DCM). Also, patients with unexplained cardiac arrest (CA) and family members of SCD victims are evaluated by this clinic. Patients with HCM are not routinely followed up by the IAC. Therefore, only genetic but not follow-up data of these patients are included in this study.

To facilitate familial cascade screening, once a patient is diagnosed or in the case of unexplained CA, a lay description of the condition and referral recommendation is summarized in a letter and immediately provided to patients to share with family members. These family members were also included in this study. Children (age, <18 years) of patients seen in our clinic are followed up in the local Children’s hospital and were not included in this study.

Diagnostic work-up is tailored to the specific patient but follows a general protocol. All patients have a detailed family history taken and a pedigree constructed by a certified genetic counselor. Provocation tests used in our clinic include exercise testing and procainamide drug challenge as indicated. In the vast majority of cases, we find these tests sufficient, and therefore, intravenous epinephrine or isoproterenol is not used. According to the suspected disorder, further tests, as detailed in Table 1, are performed. Tests are typically repeated (eg, exercise treadmill) early in the evaluation and throughout longitudinal care to assess for consistency of observations or disease progression. The diagnosis of CA of unknown cause is made in the absence of a diagnostic phenotype.

Genetic testing of patients is performed only in selected cases with probable diagnoses after comprehensive evaluation in the clinic and according to published guidelines.^3,4 All patients undergoing genetic testing were counseled by a genetic counselor, and informed consent was obtained before testing. In the province of Ontario, all tests were paid for by the Ministry of Health and performed only in certified commercial laboratories. All genetic test results are interpreted by the physician director and genetic counselor of the clinic and routinely use the following step-wise protocol:

On the basis of information gleaned from these sources, the genetic change is categorized with reference to the recommendations by the American College of Medical Genetics and Genomics. In cases of uncertain interpretation, this categorization is re-evaluated during follow-up meetings, including consideration of familial segregation and updated public databases or medical literature.

Follow-up period and the number of family members screened are presented as median+interquartile range (IQR). All other results are presented as mean±SD.

This study was approved by the institutional research ethics board.

Between 2005 and 2014, 720 patients from 473 families were evaluated. These included 367 primary referrals and 353 family members. Main reasons for referrals were (1) possible diagnosis of LQTS, (2) possible diagnosis of BrS, and (3) for the observation of frequent premature ventricular contractions or non-sustained ventricular tachycardia observed on Holter monitoring or exercise treadmill with normal left ventricular imaging. No referrals specifically questioned the diagnoses of CPVT or SQTS. The majority of patients were assessed for primary electric syndromes (n=272) or ARVC (n=188), constituting 64% of the cohort. The remaining referral cohort was comprised of previously diagnosed HCM (29%), familial DCM (2%), unexplained CA or syncope (5%), or for evaluation of SCD of unknown cause in the family (5%).

A definite or probable diagnosis was made in 71% of patients evaluated for primary electric diseases (60% of diagnoses were LQTS, 31% BrS, 7% CPVT, and <1% SQTS or early repolarization syndrome) and 61% of those evaluated for ARVC. Familial cascade screening occurred to the greatest extent when a pathogenic/likely pathogenic mutation and history of SCD/CA in the family was present (median, 3 family members/index case; IQR, 3). In the absence of familial SCD and identified mutation in the family, reflecting a less certain clinical diagnosis in the index case, clinical screening of relatives was the lowest (median, 1; IQR, 3).

Overall, on the basis of clinical and genetic data, family members of diagnosed index cases evaluated in our clinic received a definite diagnosis in 33% of the cases. In 53%, the primary diagnosis made in the index case was excluded. In 14%, definite diagnosis or exclusion could not be achieved and the patient received a possible diagnosis. Specifically, among family members who had a complete work-up for LQTS, 53% were diagnosed as affected and 47% had the diagnosis of LQTS excluded. For BrS, 20% of family members were diagnosed and 80% had the diagnosis excluded. For CPVT, 57% and 43% of family members were diagnosed or excluded, respectively.

In ARVC, only 22% of family members received a definite diagnosis, in 23%, the diagnosis was excluded, and in 19%, the diagnosis was deemed possible. In another 36%, all clinical tests were found to be normal; however, continued follow-up was recommended because of the possible development of phenotype with age. This latter group included only family members of index cases without a definite disease-causing mutation enabling exclusion of the disease.

Management of patients with overt phenotypes or gene carrier status was patient and disease specific. All patients diagnosed with an inherited arrhythmia syndrome or cardiomyopathy had the following issues discussed: (1) education on the genetics of the condition and inheritance risks, (2) review of exercise regimen and desires, with patient-specific exercise prescription (in general, moderate exercise is usually allowed), (3) recommendations for medication, (4) option of implantable cardioverter-defibrillator (ICD) implantation, and (5) drug avoidance counseling with reference to public websites (eg, http://www.brugadadrugs.org and http://www.crediblemeds.org). Patients with BrS were advised to rapidly treat fever with acetaminophen and to avoid hot tubs and saunas. In asymptomatic ARVC patients with manifest PVCs (>500 on 24-hour Holter) or treadmill-induced PVCs, β-blocker therapy was routinely initiated, as well as exercise prescription. All patients with LQTS or CPVT were prescribed β-blocker therapy, with dose titration based on response to sinus rate (LQTS) or PVC burden (CPVT) during repeated exercise treadmills.

Patients were advised of the option for referral to a psychologist to assist in coping with their new diagnosis. In addition, letters of information using lay terminology were provided to all patients reviewing discussion points from their clinic visit. A second letter is provided to patients for the purpose of sharing with family members, describing the risks of the condition and encouraging appropriate evaluation. All patients were provided a contact number for the clinic and encouraged to call for concerns over recently prescribed medications or desire to change physical exercise regime. Decisions on ICD usage for primary prophylaxis in patients deemed low to moderate risk were made only after detailed discussion with the patient in the context of estimated event risk and device complication risk and were based primarily on patient preference rather than direct physician recommendation. In patients deemed at high risk for a cardiac event ICD was recommended. Patient risk was routinely reassessed longitudinally in the clinic based on new clinical history and repeated testing, and changes in management (medication dosage, usage, and ICD treatment) were made accordingly. Finally, all lifestyle modifications were reiterated and discussed on clinic follow-up visits.

The majority of patients (with the exception of patients with HCM) referred to the IAC continued with longitudinal care for primary management of their condition. Typically, patients with a confirmed diagnosis or gene-positive carrier status had 3 visits during the first year for the purposes of reassessing risk status, psychological coping, drug compliance, and exercise regimen. Thereafter, patients were followed up annually for clinical review and re-evaluation of preventative strategies. Annually, in addition to ECGs, patients underwent 48-hour Holter, exercise treadmill, or SAECG, depending on the specific condition (Table 1). Asymptomatic ARVC patients with positive genetic findings undergo repeat magnetic resonance imaging at 3- to 5-year intervals. When appropriate, repeated genetic testing because of expansion of genetic panels was contemplated during follow-up. Data on cardiac events and ICD complications were routinely added to the clinic’s database. Cardiac events were defined as syncope of suspected arrhythmic origin, documented sustained ventricular arrhythmias, or appropriate ICD therapy.

Genetic testing was performed in 338 index referrals. Overall, pathogenic or likely pathogenic genetic variants were found in 139 (41%), genetic variants interpreted as benign or likely benign were found in 156 (46%), and variants of uncertain significance (VUS) in 58 (17%). In another 6 index cases with suspected LQTS, genetic variants associated with drug-induced LQTS were identified (2%). The yield of genetic testing among diagnosed probands was the highest in LQTS (90%) and the lowest in HCM (31%; Figure 1). In ARVC and BrS, 45% and 43% of probands tested were found to have a pathogenic/likely pathogenic mutation. More than 1 mutation was found in 4% of patients with gene-positive LQTS. In 17% of patients with gene-positive ARVC, a VUS was found in addition to a pathogenic mutation. No cases of 2 clearly pathogenic mutations were found in the ARVC group.

In HCM, the most common gene with pathogenic/likely pathogenic variants was MYBPC3 (41%) followed by MYH7 (33%; Figure 2). In LQTS, KCNQ1 mutations were most common (50%), followed by KCNH2 (46%) and SCN5A (4%; Figure 2). No pathogenic or likely pathogenic mutations were identified in any of the other reported genes associated with LQTS (KCNE1, KCNE2, AKAP9, ANK2, CACNA1C, CAV3, KCNJ2, SCN4B, and SNTA1), and only 2 cases had a VUS in these uncommon genes (1 each in CACNA1C and AKAP9). In BrS, all mutations but 1 were in the SCN5A gene. In a single patient, a previously described mutation in GPDL-1 was found (c.839C>T, p.A280V).

In probands with a definite diagnosis of ARVC based on Task Force Criteria, mutations were most commonly found in PKP2 (77%) followed by DSC2 (15%) and DSP (8%; Figure 2). Of these mutations, 80% were radical and 20% missense.

A comprehensive list of all pathogenic/likely pathogenic genetic variants and VUSs in all conditions is detailed in Tables I and II in the Data Supplement, respectively.

Long-term follow-up was recommended in 310 patients. Patients were followed up for a median of 4.1 (IQR, 4.6) years with 43% being followed up for >5 years. Of the patients followed up, 47% were seen for primary electric diseases, 37% for ARVC, 8% for CA of unknown cause, 5% for SCD of a family member, and 3% for familial DCM.

Overall, 30 patients had arrhythmic events: 22 patients received appropriate ICD shocks, 2 patients received appropriate antitachycardia pacing therapy, 2 had documented arrhythmias, 3 patients had syncope suspected of being of arrhythmic origin and received an ICD, and 1 patient had SCD at the age of 69 years. Overall, through a follow-up of 1671 patient-years, there was a single event of SCD (Figure 3).

Among family members evaluated through cascade screening, 79 received a definite diagnosis based on clinical or genetic findings. Over a median follow-up period of 5.5 years (IQR, 4.8; 55%, >5 years), a cardiac event occurred in a single patient with BrS (appropriate device therapy for monomorphic VT), whereas no sudden deaths have occurred.

Longitudinal care has been provided for 88 patients with definite or probable LQTS for a median of 4.6 years (IQR, 4.7) with 44% being followed up for >5 years. The majority of patients with LQTS were women (73%), and average age at the time of first encounter was 40±14 years. Of these patients, 29 patients (33%) had a history of a cardiac event (CA, documented torsade de pointes, syncope, or seizure) leading to assessment in the IAC. Nine patients received an ICD for secondary prevention (1 lost to follow-up). A single patient received appropriate ICD shocks, and 3 had device-related complications (1 patient with inappropriate shock, 1 with lead fracture, and 1 with device infection necessitating extraction). No patients experienced SCD or arrhythmic syncope during long-term follow-up. Two patients had syncope consistent with a vagal cause while being treated with β-blockers. No change in therapy was initiated for either patient. During a follow-up of 520 patient-years, mortality remains at 0.

Thirty patients have been followed up because of BrS (spontaneous or provoked type 1 pattern for a median of 5 years (IQR, 3.6), with 50% followed up for >5 years. Although we report on the outcomes of these patients with a definitive type 1 pattern, we may have underestimated the number of BrS cases from our unexplained CA cohort because of the decreased sensitivity of procainamide provocation when compared with other sodium-channel blockers. The majority of patients were men (71%), and average age at the time of first encounter was 48±15. Eight (27%) patients had a history of cardiac events (CA or syncope). Eleven patients received an ICD, 3 for primary prevention and 8 for secondary (2 lost to follow-up). Two patients (7%), both with a history of CA, received appropriate ICD therapy for polymorphic VT. A third patient received appropriate antitachycardia pacing for monomorphic VT during exercise at the age of 76. In 1 patient, shocks were recurrent over time and have been successfully treated with oral quinidine. One patient (primary prevention) had a device-related complication (inappropriate shocks because of lead fracture). Throughout follow-up, a single previously asymptomatic individual experienced an SCD. This patient was a 69-year-old man with multiple comorbidities, including psychiatric illness, diabetes mellitus, and vascular disease. No autopsy was performed to rule out any other possible mechanisms of death. He was found to have a type I Brugada pattern in the setting of lithium toxicity but only type II pattern during repeated follow-up. Overall, BrS patients not undergoing ICD implantation followed up for 87 patient-years had an annualized mortality rate of 1%.

Ten patients have been followed up for CPVT for a median of 3.2 years (IQR, 8.8; 4 patients for >5 years). Forty percent were men, and average age at the first encounter was 38±20. Three patients had a history of syncope thought to be from an arrhythmic cause. A single patient had recurrent syncope while being treated with β-blockers. Three patients received an ICD for secondary prevention and did not receive device therapy or complications during follow-up. No deaths have occurred.

Patients recommended for long-term follow-up included those found to have definite/possible ARVC or positive genetic findings during cascade family screening. One hundred four patients were followed up for a median of 3.8 years (IQR, 4.8) with 44% followed up for >5 years. Fifty three percent were women, and average age at the time of first encounter was 40±16 years. Twenty-three patients (22%) had a history of a cardiac event (CA, documented sustained ventricular arrhythmias, or syncope thought to be of arrhythmic cause).

During follow-up, 3 patients with a definite diagnosis were documented to have sustained ventricular arrhythmias or had syncope thought to be of arrhythmic origin and subsequently underwent ICD implantation. In total, 30 patients received an ICD (5 lost to follow-up) but only 7 for primary prevention. During follow-up, 8 patients received appropriate ICD shocks. No patients with primary prevention ICDs received appropriate shocks. Seven patients had device-related complications (6 patients had inappropriate shocks, 2 had lead dislodgement, 1 required extraction because of infection, and 1 had lead fracture).

Seventeen patients were followed up for genetic findings alone (normal clinical testing) discovered as part of familial cascade screening. During a median follow-up period of 2.8 years (IQR, 1.1), no cardiac events were documented in this subgroup.

Eighty-one patients received ICDs, 11 for primary prevention and 70 for secondary prevention. Nine of these patients were referred to our clinic from other territories and had device follow-up in their local clinics. Thus, 72 of the 278 patients (26%) followed up in our clinic had an ICD implanted. Indications for implantation included LQTS in 9 patients, BrS in 11, CPVT in 3, SQTS in 1, ARVC in 30, CA of unknown cause in 23, and DCM in 4 (Table 2). Of these indications, 58 patients underwent ICD implantation for secondary prevention in BrS, SQTS, ARVC, DCM, or CA of unknown cause. Another 5 patients received an ICD because of LQTS or CPVT and syncope while treated with β-blockers. Two patients with LQTS had syncope and β-blocker intolerance, and 1 patient with DCM had a CRT-D (cardiac resynchronization therapy/defibrillator) device implanted for heart failure and primary prevention. Thus, 66 of the 81 patients who underwent ICD implantation had a class I or IIa indication for this procedure.¹⁴ Patients with nonclass I/IIa indications for ICD implantation included 4 with LQTS and 1 with CPVT who had syncope while not treated with β-blockers. Reasons for this decision in LQTS patients included LQT3 in 1, syncope with severe injury in 1, and patient preference in 3. Seven patients with ARVC and 3 with BrS received an ICD for primary prevention because of patient’s preference.

In total, 72 patients with ICDs were followed up in our clinic for a median of 7.9 years (IQR, 6.6). Twenty-four patients received appropriate ICD therapy (33%; 5.6% annualized incidence of the first therapy). In 61 patients with a class I/IIa indication for ICD implantation followed up in our clinic for 8.1 years (IQR, 6.9), 23 received appropriate ICD treatments (38% of patients; 6.2% annualized risk). Among those without class I/IIa indications, 11 were followed up in our clinic for a median of 5.2 years (IQR, 5.5) and 1 received an appropriate ICD treatment (9% of patients; 1.8% annualized risk of the first event). This single patient had asymptomatic BrS and had an indication for permanent pacing. He underwent ICD implantation because of his preference with 1 event of antitachycardia pacing for rapid monomorphic VT during follow-up.

Device-related complications occurred in 17 patients (24%); inappropriate shocks occurred in 14 patients (20%), lead fractures in 4 (6%), lead dislodgement necessitating repositioning in 2 (3%), device infection in 2 (3%), and thrombosis of the subclavian vein, thrombi formation on ICD lead, and device malfunction in 1 patient each.

SCD is the most feared adverse event in patients with inherited arrhythmia syndromes and cardiomyopathies. Despite the appropriate diagnosis of patients, significant mortality rates have continued to be observed in previously reported long-term follow-up studies. In >350 LQTS patients appropriately being treated with β-blockers, 55 patients (16%) were reported to have recurrent cardiac events for over an average 5-year follow-up, including 33% with CA or sudden death.¹⁵ In BrS, Brugada et al¹⁶ reported that patients without a history of CA have a 4.1% per year incidence of ventricular fibrillation or death after a diagnosis. More contemporary long-term follow-up studies from registry data have indicated a lower but not insignificant risk of cardiac events in patients with a history of syncope (1.5%–1.9% per year) or completely asymptomatic patients (0.5% per year).^17,18 Similarly, in patients diagnosed with ARVC, 5.4% of patients died suddenly during 8 years of follow-up.¹⁹

In our clinic, among 278 patients managed for a variety of inherited arrhythmia disorders and followed up for a median of 4.1 years (43%, >5 years; 1671 patient-years), only a single patient died suddenly at the age of 69, and most probably because of a cause unrelated to his drug-induced Brugada ECG pattern. This low sudden death rate is favorably comparable with reported mortality rates for these conditions, particularly in view of a low rate of primary prevention ICD utilization in our clinic. Only 11 patients (4%) received ICDs for primary prophylaxis of SCD. In families of patients with CA or SCD of unknown cause followed up in our clinic, there have been no cardiac events. These data are in line with previous studies demonstrating good prognosis in this subset of patients²⁰ and may provide reassurance that although the cause is unknown, the prognosis of family members is favorable.

Although estimating the actual number of lives saved by a specialized IAC is extremely difficult, this low incidence (0.1% annualized risk of SCD) may be at least partially explained by the effectiveness of management in a dedicated inherited arrhythmia program. In the specialized clinic, patients receive clinical assessment and longitudinal care by physicians with a high-volume experience on these uncommon conditions, enhancing expertise in the diagnosis, risk stratification, management, and decision making for these patients. This model may partially explain the low event rates in our cohort compared with reported outcomes derived from registry data where patients typically receive longitudinal care by physicians with varying expertise or clinical volumes for these specific conditions.

The advantages of a specialized clinic have been highlighted in the diagnosis and management of LQTS. Taggart et al²¹ reported on the clinical experience of the Mayo LQTS clinic in the assessment of 176 patients referred after a diagnosis of LQTS. Over 40% of these patients had the diagnosis of LQTS removed, and more than half of these cases were wrongly diagnosed by arrhythmia specialists. Importantly, 7% of these cases inappropriately received an ICD for their incorrect diagnosis and 5% of the cohort subsequently received an alternative diagnosis, including CPVT. Viskin et al²² have reported on the challenges faced by cardiologists, including arrhythmia specialists, in correctly measuring the QT interval and classifying measurements as prolonged or normal. Using ECGs from confirmed LQTS cases and healthy controls, <25% of general cardiologists correctly classified ECGs. Although the success rate was higher for arrhythmia specialists, almost 40% made incorrect conclusions. Similar challenges may be expected to occur for clinicians who only occasionally are requested to evaluate and diagnose the less common conditions of CPVT and ARVC. Overdiagnosis of any of these conditions may lead to inappropriate interventions associated with significant morbidity, both physically and emotionally. Underdiagnosis may lead to tragedy and the absence of preventative measures for at-risk family members. The focused, multidisciplinary approach ensures appropriate education and counseling of affected patients, providing lay-term written summaries to patients describing their condition and treatment approach. This communication also facilitates appropriate cascade screening of family members. Early and regular follow-up after a diagnosis ensures treatment compliance and ongoing risk stratification and provides the opportunity to reassess psychological well being in light of a life-changing diagnosis. Although this specialized clinic approach represents many advantages to patient care, it remains uncertain that these advantages translate into decreased mortality and morbidity. However, in light of only a single death in a 69-year-old patient with incidental drug-induced BrS and our low annualized mortality rate of 0.1% in comparison with published rates for LQTS, BrS, and ARVC,^15,17–19 we postulate that a dedicated, multidisciplinary IAC may impart benefit to long-term survival.

Among patients who underwent ICD implantation and followed up in our clinic, the annualized incidence of first appropriate therapy was 5.6%. All but 1 patient receiving device therapy had a class I/IIa recommendation for ICD implantation. Only 11 patients (4%) received primary prevention ICDs (7 for ARVC, 3 for BrS, 1 for DCM, and 0 for LQTS and CPVT). Over a median follow-up of 5.2 years, only 1 of these patients received appropriate device therapy. These results are similar to those of a previous study that demonstrated that almost none of the patients with LQTS or BrS who underwent ICD implantation for primary prevention received appropriate therapy by the device.²³ These data may reassure us that the majority of these patients with potentially lethal conditions may be managed successfully without ICD implantation. Furthermore, the high rate of device-related complications in this young and active population²⁴ (24% during 8 years of follow-up in our cohort) emphasizes the need for a cautious approach toward ICD implantation without a robust indication.

Cascade screening is of major importance as it enables diagnosis of at-risk individuals before cardiac events. In our clinic, in patients with a clinical diagnosis, positive genetic testing, and a family history of SCD, a median of 3 relatives per index case were screened (IQR, 3). However, routine familial screening was not limited to this clinical scenario and was extended to family members of index cases without a family history of SCD or definitive genetic finding. Overall, in about half of family members screened, the primary diagnosis made in the index case was excluded. In a third of the cases, the family members received the primary diagnosis. In the remaining 14%, definite diagnosis or exclusion could not be made. Retrospective review of disease cohorts identified numerous issues leading to the differences in diagnostic yields for each condition, including the challenges in clinical phenotyping, genetic testing yield and interpretation (eg, VUS rate), and variable penetrance of disease unique to each condition. In LQTS, BrS, and CPVT, familial screening was more straight-forward because of the high clinical utility of treadmill testing (LQTS and CPVT) or intravenous drug provocation (BrS) coupled with more reliably interpretable genetic testing results. The number of family members receiving a definite diagnosis or exclusion was especially small in the ARVC group (45% combined diagnosis+exclusion). In these patients, genetic results’ interpretation is often not straight-forward, and phenotype may emerge only at an older age making definite diagnosis or exclusion more difficult. In general, a greater proportion (>50%) of family members related to an ARVC index case required ongoing medical surveillance and screening to assess for the disease presence.

In our clinic, 40% of probands were found to have a pathogenic or likely pathogenic mutation. This finding is comparable with the result of a large study recently published²⁵; in which, 31% of families analyzed were found to harbor a possible disease-causing mutation. In patients with LQTS, HCM and ARVC the most common genes to harbor mutations (KCNQ1, MYBPC3, and PKP2, respectively) were similar to those found in other cohorts.^7,26,27

The yield of genetic testing in our clinic for probands with ARVC (45%) was similar to that reported in previous studies.⁴ In LQTS (90%) and BrS (43%), it was slightly higher than previous reports.^4,8,27 Our increased yield of genetic testing for LQTS and BrS may reflect a more rigid phenotyping or diagnostic approach and prudence in genetic testing utilization. Typically, genetic testing in our clinic is performed for these conditions only when diagnostic testing reveals consistent and clear phenotypes. In the HCM group, the yield of genetic testing in probands was relatively low.⁴ As patients with HCM are not phenotyped in our clinic but rather referred solely for genetic testing, this may have resulted in a lower threshold for genetic testing and subsequently a lower yield. It is, therefore, probably preferable that clinical and genetic evaluation be done in the same clinic to minimize the costs of unnecessary genetic testing.

This study evaluated the outcome only of patients assessed and followed up long term in our clinic. It is possible that adverse events occurred in patients evaluated in whom follow-up was not deemed necessary. Furthermore, ≈10% of patients received follow-up elsewhere, primarily for geographical reasons, and may have had cardiac events. Nevertheless, in Ontario, it is customary for all physicians treating a specific patient to receive copies of relevant letters concerning the patient’s health even when follow-up is occurring elsewhere. Furthermore, information on all patients who have a family member followed up in the clinic was partially available as during follow-up visits, data on cardiac events in the family are also gathered. This does not exclude the possibility of missed cardiac events but does significantly reduce this possibility.

Theoretically, estimation of SCD events averted by a specialized IAC would require data of SCD events before and after the foundation of such a clinic. Unfortunately, such precise data are lacking in our region and probably in most other regions in which such a clinic has been developed. Nevertheless, our results of an SCD rate of 0.1% per year are low enough to imply a considerable yield of such a clinic, particularly in comparison with published event rates with comparable follow-up periods.

A dedicated IAC may provide expertise in the diagnosis, genetic testing interpretation, and management of patients and families with suspected arrhythmia syndromes and is associated with a low cardiac event rate. Low event rates occur despite a relatively low rate of ICD utilization for primary prevention. Intuitively, during the lifetime of the clinic, a significant number of at-risk patients have been identified with the implementation of education and preventative strategies, which may decrease SCD rates in younger individuals from our region in future decades.