Discussion
Our patient experienced cardiac arrest secondary to ERS. Diagnosis requires the presence of an early repolarisation pattern on the ECG, together with arrhythmias in the form of either polymorphic ventricular tachycardia or ventricular fibrillation (3). Other potential causes of polymorphic ventricular tachycardia and ventricular fibrillation must be ruled out, and no structural heart disease should be present.
An early repolarisation pattern is characterised by J waves, which may be well-defined or manifest as fragmentation or distortion of the terminal portion of the QRS complex (Figure 5). The presence of an early repolarisation pattern does not necessarily require ST-segment elevation on the ECG, although this is often observed (4).
Many patients exhibit some degree of ST elevation in the precordial leads (typically V2–V3), which is often incorrectly classified as early repolarisation. Isolated ST elevation without distinct J waves should not be interpreted as an early repolarisation pattern and has no established prognostic significance.
Early repolarisation pattern on ECG is common and frequently observed in healthy patients. Historically, early repolarisation was considered a benign finding. However, in two studies of patients with idiopathic ventricular fibrillation, a correlation was observed between this condition and early repolarisation on ECG in 31 % (5) and 60 % of patients (6), respectively. By comparison, early repolarisation pattern was observed in only 5 % and 3.3 % of the control groups.
The prevalence of early repolarisation varies with age, sex and ethnicity, and is particularly common in younger men and athletes. Because early repolarisation is common in the general population while idiopathic ventricular fibrillation is rare, the presence of an early repolarisation pattern on an ECG is generally considered an incidental finding with no clinical significance (4). The risk of idiopathic ventricular fibrillation in individuals under 45 years of age is approximately 3 per 100,000 person-years, increasing to 11 per 100,000 person-years in patients with J waves (7).
Our patient exhibited a typical clinical presentation, ECG findings and dynamic ECG changes consistent with ERS. ERS shares several features with Brugada syndrome. Both conditions are associated with J waves on the ECG and an increased risk of sudden cardiac death. In Brugada syndrome, J waves are confined to the right precordial leads (V1–V3) and can mimic ST-segment elevation. In ERS, J waves are primarily observed in the inferior leads. Together, Brugada syndrome and ERS are classified as J-wave syndromes (3).
J waves are caused by a voltage gradient between the epicardial and endocardial myocardium (4). These voltage differences are primarily influenced by regional variations in the density of potassium channels responsible for the current underlying early repolarisation. Mutations in the genes encoding these ion channels can alter the channels' function. Both Brugada syndrome and ERS are ion channelopathies, with causal mutations identified to varying extents. In addition to genetic mutations, other factors, such as medications, body temperature, electrolyte disturbances and neurohormonal fluctuations, can modulate ion channel function. The interaction of these factors explains the dynamic behaviour of J waves often observed in patients with Brugada syndrome and ERS.
J waves can be observed in a variety of conditions and were first described in 1920 in association with hypercalcaemia. In 1953, Osborn conducted animal studies demonstrating that J waves are a reproducible finding in severe hypothermia (<30 °C), with the amplitude of the J wave increasing progressively with the severity of hypothermia until the onset of ventricular fibrillation (8). J waves are sometimes eponymously referred to as Osborn waves, a term commonly used for hypothermia-induced J waves. Arrhythmia in the form of ventricular fibrillation is a common cause of death in patients with hypothermia (9).
ERS, Brugada syndrome and severe hypothermia are all conditions in which prominent or augmented J waves are associated with ventricular fibrillation. In patients with J-wave syndromes, cardiac arrest most commonly occurs at rest or during sleep, as in our patient. J waves typically become more pronounced immediately prior to cardiac arrest (6), and premature ventricular complexes with short coupling intervals are typically present in the period preceding ventricular fibrillation. Post-pause J-wave augmentation is strongly associated with ventricular fibrillation in patients with ERS (4). These findings were evident in our patient (Figures 3 and 4). In ERS, the amplitude and distribution of J waves, as well as accompanying horizontal or descending ST segments, are predictive of ventricular arrhythmia.
Sudden death in young individuals is dramatic. When such events occur, follow-up is often required, which is particularly challenging when a common finding could reflect serious disease and guidance for follow-up is limited. Our patient had several siblings, and the potential need to screen first-degree relatives of patients with ERS naturally became a topic of discussion. The literature on this subject is sparse, and no clear guidelines currently exist.
Several gene mutations are associated with ERS, but the relationship between specific genetic variants and the clinical risk of ventricular fibrillation remains uncertain. Consequently, routine testing for all such mutations is not performed in cases of arrhythmic death, and systematic genetic screening of first-degree relatives of patients with ERS is not recommended (10); it was therefore not undertaken in our case. Given that early repolarisation is common in the general population, its presence in first-degree relatives has limited diagnostic value in the absence of a clinical correlate.
In our patient, genome sequencing was performed using the NGS-Cardiac Arrhythmia gene panel, which did not reveal any pathogenic variants. Most genes associated with ERS are not included in this panel. The diagnosis must be based on ECG findings and the patient's arrhythmic history, after exclusion of other potential causes. Patients with a confirmed diagnosis have a Class IA indication for an implantable cardioverter-defibrillator (ICD). As early repolarisation pattern is relatively common in the population and ventricular fibrillation is rare, an ICD is primarily indicated for secondary prevention.
Following discussions with the National Centre for Cardiac Arrhythmias at Oslo University Hospital, Rikshospitalet and the Cardiac Genetics Unit at Oslo University Hospital, we concluded that first-degree relatives of a patient with ERS who present with symptoms consistent with arrhythmia and concurrent early repolarisation on ECG should be referred for evaluation by a specialist in cardiac arrhythmias. Specialist evaluation typically involves a comprehensive assessment of arrhythmic risk, and an implantable loop recorder (ILR) may be considered as part of the follow-up (11).
ERS is a rare cause of cardiac arrest but should be considered in patients with structurally normal hearts in whom no other cause for the arrest has been identified and an early repolarisation pattern is observed on ECG. Diagnosis must be based on ECG findings and the patient's arrhythmic history, after exclusion of other potential causes. It should be emphasised that an early repolarisation pattern on ECG is common and, as an isolated finding, does not warrant further investigation. Isolated ST elevation in V2–V3 without J waves, known as 'high take-off', does not constitute an early repolarisation pattern and should not be regarded as a marker of arrhythmic risk.
It is important to remember that an ECG only gives a snapshot of the heart's electrical activity. This case illustrates the value of repeat ECGs. Even in an era of increasingly advanced diagnostic techniques, the benefit of simple, inexpensive, non-invasive investigations that can yield significant information should not be overlooked.