4. Inherited Arrhythmia Syndromes and Cardiomyopathies

Question 4: In persons with inherited cardiac conditions, diagnosed with or at risk for an inherited cardiac condition who are considering driving, what is the rate of SCD, syncope, or impaired consciousness (these conditions serve as the surrogate for SCI in this section)?

Inherited heart diseases are common causes of SCD in young individuals and are similarly associated with risk of syncope. They are globally divided into genetic cardiomyopathies and primary electrical heart diseases. Cardiomyopathies associated with a risk of SCD include hypertrophic cardiomyopathy (HCM) and arrhythmogenic cardiomyopathy (ACM). The most common primary electrical diseases include Brugada syndrome and long QT syndrome.

Fitness to drive for patients with this diverse group of diseases is determined according to the risk of VA events potentially causing impairment of consciousness or SCD (Table 4). This risk highly depends on the nature and severity of the condition. The risk of new onset or recurrent atrial or VAs and related effect on fitness to drive is highly variable, dependent on the underlying condition and its severity, with practical online risk calculators available for ACM and HCM, and numerous references on risk predictors for the remaining conditions, often termed “channelopathies.” The risk is primarily driven by symptomatic status, complimented by the severity of the phenotype, with variable input from genetic and family parameters, and sex.

Because of the lack of large-scale, detailed driving-specific data in this realm of uncommon conditions, the clinician is often faced with potential exceptions or patient nuances provided in the recommendation tables and must draw on judgement and updated evidence on risk of incapacitation to guide decision-making. Notwithstanding the language and recommendations in the guidance recommendations, the overarching precedent of accepting a < 1% 1-year risk of incapacitation represents a guiding principle that is reasonable with input from an expert, typically in a multidisciplinary clinic. This 1% standard has been upheld across this document, on the basis of accepted precedent in the 2003 guidelines and its predecessors.

Brugada syndrome

Brugada syndrome is an inherited primary electrical heart disease characterized according to a specific electrocardiogram (ECG) pattern. The diagnosis relies on the presence of the type 1 Brugada ECG pattern, either spontaneously or when challenged with a sodium channel blocker, in ≥ 1 of leads V₁ or V₂ positioned in the standard position or in higher positions. Type 2 Brugada ECG pattern is nondiagnostic for Brugada syndrome, but usually warrants expert diagnostic evaluation.

The risk of SCD with Brugada syndrome is considered low for most patients in contemporary cohorts.^[74],[75] Patients at the highest risk are those with a previous history of VA events (VT, VF, cardiac arrest) who have an annual risk of recurrence of 5%-10%^[75] followed by those with presumed arrhythmic syncope with an annual risk of VA events of 2.5%.^[76] Asymptomatic patients with a spontaneous ECG pattern are at higher risk (0.8%-1% per year) than those who only have a sodium channel-induced type 1 pattern (0.35% per year).^[75]

Long QT syndrome

Long QT syndrome is characterized according to a prolonged QT interval, which might be accompanied by abnormal T-wave morphology and can cause VA (specifically, torsades de pointes). It is an inherited cardiac channelopathy generally resulting from rare pathogenic variants in ion channel genes.^[77] The cornerstone of therapy for patients with long QT syndrome is β-blockers, along with avoidance of QT-prolonging drugs. Breakthrough events are very rare in patients who are adherent to therapy. The highest risk for VA is in those with a history of cardiac arrest, those with recurrent syncope despite use of β-blockers, and in patients with long QT type 2 and long QT type 3 harboring a QTc > 500 ms. In these latter patients, the annual risk is slightly > 1%.^[78],[79]

Arrhythmogenic cardiomyopathies

Arrhythmogenic cardiomyopathies can be defined as genetically determined cardiomyopathies that are associated with structural heart disease and a preponderance of VAs out of proportion to the degree of ventricular dysfunction. Arrhythmogenic right ventricular cardiomyopathy was the first ACM to be recognized and is the most characterized of these diseases. The diagnosis is reliant on specific criteria last published in 2010.^[80] In addition, other specific genes including Lamin, Filamin C, desmin, RNA binding motif protein 20, and sodium voltage-gated channel alpha subunit 5 are associated with a predominant left-sided disease.

Patients with a definite arrhythmogenic right ventricular cardiomyopathy diagnosis are at relatively high risk of VA events (including sustained or ICD-treated VT/VF and [aborted] SCD). Large series report a risk of approximately 5% per year.^[81] The risk of all VA events and more specifically of the most rapid subset of them (VT > 250 beats per minute, VF, [aborted] SCD) can be calculated in these patients using risk prediction models (ARVCrisk.com). Conversely, those who do not meet full diagnostic criteria, unaffected desmosomal variant carriers and minimally affected family members very uncommonly have VA events.^[82]

Among the other ACM-associated genes, Lamin is the best characterized. Recognizing the risk associated with this specific disease, guidelines and consensus documents make specific recommendations for ICD implantation.^[83],[84] An ICD should be considered (IIa recommendation) in the presence of ≥ 2 risk factors among the following: LVEF < 45%, male sex, nonsustained VT, and nonmissense variants. A risk calculator also exists specifically for this disease, with an online version available at: https://lmna-risk-vta.fr. The natural history and associated risks of other arrhythmogenic cardiomyopathies have less extensive data and thus fewer recommendations regarding management thresholds.

Hypertrophic cardiomyopathy

HCM is the most prevalent genetic heart disease, which affects at least 1 person in 500,^[85] and is one of the most common causes of SCD in the young. Two approaches to risk stratification exist. Although the European Society of Cardiology guidelines recommendation was made on the basis of a risk calculator approach, the American guidelines use a risk factor-based approach. In the European Society of Cardiology guidelines, a calculated risk of VA > 6% per 5 years warrants consideration of an ICD (IIa recommendation). The following risk factors are considered as stand-alone indications for primary prevention ICD implantation in patients with HCM: wall thickness ≥ 30 mm, truly unexplained recent syncope, otherwise unexplained systolic dysfunction (LVEF < 50%), and presence of an apical aneurysm. Importantly, the risk decreases significantly after the age of 60 years (0.2% per year).^[86]

Guidance for patients with ICDs is provided in the Inherited Arrhythmia Syndromes and Cardiomyopathies section.