br Long QT syndrome LQTS is characterized

Long QT syndrome LQTS is characterized by prolonged ventricular repolarization and susceptibility to syncope and SCD through VT (TdP), which can deteriorate into VF [25]. A clinical diagnosis is made from a combination of clinical history, family history, and 12-lead ECG, which typically reveals a heart rate-corrected QT interval (QT interval divided by the square root of the RR interval in seconds=QTc) of greater than 0.46s in women and 0.45s in men [25]. LQTS is most commonly inherited in an autosomal Epigenetics Compound Library fashion and has been associated with mutations in 15 genes. Among these, more than 75% of the mutations in congenital LQTS were of the KCNQ1 (LQT1), KCNH2 (LQT2), or SCN5A (LQT3) genes [26]. β-blocker therapy is associated with a 50% reduction in risk of cardiac events, and mexiletine is effective in LQT3 patients [27]. ICD implantation is recommended for patients with resuscitated cardiac arrest/VF or recurrent syncope who are on β-blockers. Several studies have suggested that early afterdepolarizations arising from the Purkinje network and/or myocardial fibers are the primary triggering beats in TdP [7,28–31]. For example, Haïssaguerre et al. reported four symptomatic LQTS patients diagnosed on the basis of a corrected QT interval of > 460ms who underwent catheter ablation [7]. In one patient, VPCs originating from the RVOT were ablated by RF energy applications. In three patients, VPCs originated from the left Purkinje system and were eliminated by ablation at multiple sites. During a mean follow-up period of 24±20 months, there was no recurrence of syncope, VF, or SCD in any patient, although one patient with LQTS was maintained on a β-blocker, and another had a late recurrence of VPCs. The authors concluded that the triggers from the Purkinje network or the RVOT play a crucial role in initiating TdP or VF in LQTS, and these can be eliminated by focal ablation. Other groups also reported that VPCs originating from the RV free wall and RV inferoseptal wall could trigger VT/VF and could be eliminated by focal ablation [30,31].
Catecholaminergic polymorphic ventricular tachycardia Catecholaminergic polymorphic VT (CPVT) is an inherited arrhythmogenic disorder characterized by polymorphic VT induced by physical or emotional stress with no detectable morphological abnormalities in the heart [32]. To date, five genes, cardiac ryanodine type 2 receptor (RYR2), calsequestrin 2 (CASQ2), KCNJ2 (which encodes Kir2.1), calmodulin 1 (CALM1), and triadin (TRDN), have been identified as being involved in CPVT [33]. Typical arrhythmias include bidirectional VT and polymorphic VT that can degenerate into VF and thus SCD. β-blockers and additional administration of flecainide or verapamil have been reported to be effective for the prevention of VT/VF [34]. An ICD is considered the definitive therapy for the prevention of SCD, although failure of the ICD to prevent SCD has been reported in several cases because the ICD shock delivery might lead to catecholamine release, resulting in an electric storm [35]. Cerrone et al. reported that the mechanism of CPVT was due to delayed afterdepolarization‐induced triggered activity in a focal Purkinje network in a knock-in (RyR2) mouse [36]. In addition, chemical ablation of the RV endocardial cavity with Lugol׳s solution, which selectively destroys the Purkinje network, could convert bidirectional VT into monomorphic VT in a CPVT model of anesthetized mice. Therefore, the Purkinje network is considered to be a critical contributor to arrhythmogenic triggers in CPVT and may be a promising therapeutic target for catheter ablation. Our group presented the first case report of the successful catheter ablation of bidirectional VPCs triggering VF in patients with CPVT [37]. This case was of a 38-year-old woman who had often experienced syncope since childhood. The patient׳s daughter also had similar episodes of syncope and developed VF during treadmill exercise testing, which was successfully defibrillated with an electric shock. Witnessing this situation, the patient also lost consciousness, with documented VF which was converted to sinus rhythm by cardiopulmonary resuscitation. There were no significant abnormalities in her resting 12-lead ECG, echocardiography, or coronary angiography. Genetic analysis revealed that she and her daughter had same missense mutation (c.1259G>A, p.R420Q) in RyR2, and both were diagnosed as having CPVT. During the patient׳s epinephrine stress test (Fig. 1), multifocal VPCs (VPC #1, RBBB, and superior axis; VPC #2, RBBB, and inferior axis, the same VPC configuration as that induced during the treadmill exercise testing; and VPC #3, LBBB, and inferior axis) appeared, and VPC #1 following VPC #2 subsequently induced VF. We performed catheter ablation targeting the catecholamine-induced VPCs (Fig. 2). VPC #1 was recorded at the left ventricular inferoseptal area near the posteromedial papillary muscle, where a presystolic Purkinje potential preceded VPC #1 by 18ms. RF energy application to this site accelerated the VPCs, and additional applications around the target site subsequently eliminated VPC #1. After the procedure, VPC #2 continued to occur, and a local bipolar electrogram recorded on the left coronary cusp showed a discrete prepotential that preceded the onset of VPC #2 by 65ms. RF energy application to the left coronary cusp abolished VPC #2. After ablation at both sites, neither the VPCs nor VF was inducible, even with an infusion of epinephrine at up to 1.2g/kg per min. The patient underwent ICD implantation and was discharged from the hospital on bisoprolol. During a 16-month follow-up after ablation, no episodes of syncope or ICD therapy occurred. Thus, catheter ablation of the bidirectional VPCs triggering VF may become an adjunctive therapeutic option for CPVT.