Discussion

Concomitant hypertrophic cardiomyopathy and Wolff–Parkinson–White syndrome is a very rare condition, with most reports in the literature on familial form related to a PRKAG2 mutation.Reference Porto, Brun and Severini ¹ Our patient presented with aborted sudden death due to ventricular fibrillation, and was found to have sporadic hypertrophic cardiomyopathy and Wolff–Parkinson–White syndrome with clearly documented Kent bundle-mediated supraventricular tachycardia.

We found that this is the first description of either TNNT2 variant or double mutation in a patient with concomitant hypertrophic cardiomyopathy and Wolff–Parkinson–White syndrome. The p.Arg94Thr variant in TNNT2 was an unregistered de novo mutation predicted to be deleterious by in silico analysis. So far, cardiac troponin I, MYBPC3, and β-myosin heavy chain (MYH7) mutations have been identified in this rare condition, but their causal association with Wolff–Parkinson–White syndrome itself remained undetermined because pre-excitation wave was not present in all affected family members of cardiac troponin I and MYBPC3,Reference Kimura, Harada and Park ² and MYH7 mutation case was a sporadic disease without familial involvement.Reference Bobkowski, Sobieszczanska and Turska-Kmiec ³ Considering the well-established pathogenic role of MYBPC3 and TNNT2 genes in the development of hypertrophic cardiomyopathyReference Elliott and Anastasakis ⁴ and the sporadic nature of this case, we could not conclude whether the observed double mutation was responsible for both diseases, or it was an incidental Wolff–Parkinson–White syndrome co-existing with hypertrophic cardiomyopathy.

Several mechanisms can be proposed for the development of the ventricular fibrillation in this patient: 1) supraventricular tachycardia-related haemodynamic compromise, 2) pre-excited atrial fibrillation, and 3) primary ventricular tachyarrhythmia. An association between supraventricular tachycardia and sudden cardiac death in hypertrophic cardiomyopathy patients has been well acknowledged for years. Furthermore, there is direct electrophysiological evidence documenting its fatal consequence; rapid repetitive conduction to ventricles during supraventricular tachycardia, for example re-entrant tachycardia, atrial fibrillation, and even sinus tachycardia, resulting in spontaneous rhythm degeneration into ventricular fibrillation.Reference Munclinger, Thornton, Schutte and Sliwa ^{5 –} Reference Elliott, Sharma, Varnava, Poloniecki, Rowland and McKenna ⁷ Aggravating factors responsible for this phenomenon include inherent vulnerability to ischaemia due to myocardial mass, left ventricular outflow tract obstruction, and abnormal vascular response, which were all present in our case and might play a synergistic role.Reference Stafford, Trohman, Bilsker, Zaman, Castellanos and Myerburg ^{6 ,} Reference McKenna and Behr ⁸ Fast pre-excited atrial fibrillation is also a well-known cause of sudden cardiac death in the young; however, our electrophysiology study revealed a Kent bundle refractory period of more than 300 ms and no inducible atrial fibrillation; thus the ventricular fibrillation seemed less likely to be related to atrial fibrillation.Reference Priori, Blomstrom-Lundqvist and Mazzanti ⁹ Lastly, fast polymorphic ventricular tachycardia was induced once during the test. However, programmed extra-stimulation-induced ventricular arrhythmia has limited prognostic significance in hypertrophic cardiomyopathy,Reference Priori, Blomstrom-Lundqvist and Mazzanti ⁹ and the ventricular tachycardia was not reproducible despite multiple repeated stimulation; therefore it could be regarded as idiosyncratic reaction to aggressive stimulation protocol. Nevertheless, the possibility of primary ventricular tachyarrhythmia could not be ruled out.

Although implantable cardioverter/defibrillator is considered the first-line treatment option for sudden cardiac death survivors with hypertrophic cardiomyopathy, current guideline, on the contrary, recommends electrophysiology study for those with ventricular pre-excitation to identify and treat an ablatable substrate.Reference Priori, Blomstrom-Lundqvist and Mazzanti ⁹ Proper discretion is particularly required when implanting the implantable cardioverter/defibrillator in the young, because they are more likely to suffer from inappropriate shock, psychological distress, and poorer quality of life than elderly, which can paradoxically potentiate sudden death risk.Reference Priori, Blomstrom-Lundqvist and Mazzanti ^{9 –} Reference Lampert, Salberg and Burg ¹² Indeed, our patient refused to undergo implantable cardioverter/defibrillator therapy due to concern about its impact on his future employment. Implantable cardioverter/defibrillator therapy should be the first choice for secondary prevention, however, upon his refusal, we decided to eliminate the anatomical arrhythmogenic substrate, which we thought could potentially reduce the risk of new events. Nevertheless, the importance of lifelong monitoring and periodic risk re-evaluation can never be emphasised enough for this young man. Further studies using global registry are required to determine the optimal strategy for the sudden cardiac death survivors who have multiple predisposing conditions and correctable causes.