Cardiovascular Journal of Africa: Vol 32 No 6 (NOVEMBER/DECEMBER 2021)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 32, No 6, November/December 2021 AFRICA 295 pattern in patients with paroxysmal supraventricular tachycardia (PSVT). 8 Years later, the term ‘pre-excitation’ was introduced as a phenomena whereby, in relation to atrial events, the whole or part of the ventricular muscle is activated earlier by the impulse originating in the atrium than would be expected if the impulse reached the ventricles by way of the normal conduction system. 9 WPW remains the most common variety of pre-excitation syndrome. The classic ECG in theWPWsyndrome is characterised by a short PR interval (< 120 ms) and a prolonged QRS duration. The initial slurring of the upstroke of the QRS complex (delta wave) represents the anomalous excitation of the ventricle, with muscle–muscle conduction bypassing the normal pathway. Clinical features of the WPW syndrome are variable among patients; a spectrum occurs that manifests from no symptoms to sudden cardiac death. Both atrial and ventricular arrhythmias may occur in this group of patients. If atrial disorganised high- frequency electrical impulses transmit to the ventricle through the accessory pathway during AF episodes, sudden cardiac death due to ventricular fibrillation is inevitable. Therefore, AF inducibility is one of the risk factors for WPW patients. 4 In recent studies, AF inducibility was investigated in both animal and human heart models. 10,11 Authors have emphasised c-Jun N-terminal kinase (JNK) in their work. Advancing age and other stresses, such as excessive alcohol use, obesity and inflammation, drive JNK activation and the JNK/CaMKII interaction is likely a critical mechanism that couples arrhythmia and these stresses (Ca 2+ /calmodulin directly phosphorylates CaMKII proteins, driving CaMKII pro-arrhythmic effects on diastolic-dependent kinase II). Activated JNK2 decreases SR Ca 2+ handling. Authors have shown that in JNK-challenged animal models, AF propensity was eliminated by JNK2 ablation or CaMKII inhibition. Beyond obesity and excessive alcohol consumption, the literature is not rich on the relationship between augmented JNK2 activity and other pro-arrhythmic conditions such as co-existing accessory pathways and genetic mutations (long- QT syndromes). Furthermore, it has not been studied whether emotional or physical stress (endurance sport) affect JNK activity in the same way as the other stressors mentioned. At this point, JNK is worth investigating to explain AF inducibility in young WPW patients. Another reason for sudden cardiac death is ventricular arrhythmias, ventricular fibrillation in particular. Idiopathic ventricular fibrillation and other malignant arrhythmias are not rare in these patients and they may occur spontaneously without preceding AF. 12 To understand the mechanism at play here, a basic model would be helpful. 13 Hypothetically, an antegrade fusion beat uses both AV node and accessory pathways, which bring non-physiological delay between ventricular depolarisation kick off. This delay may even be intraventricular and between different regions of the same ventricle. Non-uniform prolongation of the action potential duration may be pro-arrhythmic by increasing dispersion of repolarisation or refractoriness and changing the electrical gradients. For a better understanding, in vivo left ventricular hypertrophy models would be helpful. In these studies, it was shown that epicardial action potentials are more prolonged than those in the endocardium, altering the endo–epicardial gradient seen in normal hearts and associated with increased inducibility of polymorphic ventricular tachycardia or ventricular fibrillation. 14-16 Generally, radiofrequency ablation of the accessory pathway is recommended for symptomatic patients and/or individuals who undertake competitive/endurance sport and/or whose occupation is accepted to bear high risk (pilot, bus driver). A major problem for clinicians is predicting the clinical outcome in patients incidentally found with asymptomatic ventricular pre-excitation. Current guidelines recommend single or combined utilisation of risk factors such as young age, AF inducibility and short anterograde APERP. 4 However, non-invasive methods for risk stratification are limited. The intermittent appearance of delta waves on a surface ECG or Holter monitor is accepted to be a low-risk predictor. It was postulated that disappearance of delta waves may be due to acceleration-dependent block (phase 3 block) when an impulse reaches a conduction fibre during its repolarisation phase. It may also occur when an impulse reaches a conduction fibre during a time of slow diastolic depolarisation (automaticity), referred to as phase 4 block. 17 Exercising and catecholamine discharges cause an increase in the sinus rates as well as enhanced conduction through both the accessory pathway and the AV node. This may lead to different degrees of ventricular pre-excitation on the surface ECG and mask persistent pre-excitation. Abrupt and complete loss of pre-excitation during exercise has been shown to correlate with a long antegrade APERP and consequently lower risk for sudden death. However, sensitivity is low for non-rapid conducting accessory pathways and there is a need for another tool for risk stratification. 18 Furthermore, two studies retrospectively analysed a large group of asymptomatic paediatric pre-excitation patients, 19,20 and demonstrated that there was no difference in the prevalence of high-risk accessory pathways between patients with persistent pre-excitation, those with intermittent pre-excitation on baseline ECG, and those with loss of pre-excitation on Holter or exercise. With this background, we sought to find a new non-invasive risk marker for decision making in asymptomatic patients. We hypothesised that faster conduction in the accessory pathway would be the shorter measurable time interval on surface ECG. If we use a model of sinus fast-pathway conduction in a slow–fast AV re-entry model, we would expect the time interval from the occurrence of the sinus impulse (beginning of the P wave) to depolarisation of the first myocardial mass (beginning of the delta wave) (PDI) would be shorter in some ECG derivations. These derivations supposedly directly record the axis of accessory pathway conduction, which is V1 and V2 in our case. Positive–negative or negative–positive delta-wave couples are classic for septal accessory pathways. Therefore we hypothesised that PDI measurements would be more appropriate and are expected to be shorter in the above ECG derivations. When patients were grouped by APERP < 240 ms or having inducible AF or symptom status, the PDI was significantly shorter in individuals who had a shorter APERP, had inducible AF and were symptomatic. We demonstrated a strong positive correlation between PDI duration and APERP and AF inducibility in adult WPW patients. Limitations The main limitation of our study is the absence of isoproterenol in the electrophysiology protocol. A nationwide shortage of this drug