If a structurally normal patient

If a structurally normal patient with polymorphic VT/VF storm has a completely normal baseline ECG, the possible diagnosis includes CPVT and idiopathic VF. CPVT is an inherited disorder of intracellular Ca2+ handling, which can cause polymorphic VT/VF storms [10]. Abnormal SR Ca2+ release from defective ryanodine receptors produces DADs, triggering activity in the Purkinje system, which is the proposed mechanism of polymorphic VT in CPVT patients. Mutations in the gene encoding RyR2 lead to Ca2+ leak from the SR in an autosomal parp inhibitors form (CPVT1), while mutations in the gene encoding cardiac calsequestrin (CASQ2), an SR-buffering protein, lead to the less common autosomal-recessive form (CPVT2). CPVT1 and CPVT2 account for approximately 60% of CPVT patients. A history of stress or exertion-induced syncope in a young patient is suggestive of CPVT, which is usually tachycardia dependent. The hallmark of CPVT is bidirectional VT that exhibits alternating LBBB and RBBB QRS patterns. Beta-blockers are the mainstay treatment of CPVT, since beta-adrenergic stimulation increases intracellular Ca2+, which triggers DADs and polymorphic VT. An experimental study suggests that carvedilol is the most effective beta-blocker because it can directly block RyR2 with a CPVT mutation [37]. Verapamil has an additional effect on CPVT in cases of electrical storms that are resistant to beta-blockers [10]. A recent study has shown that flecainide suppresses DADs and CPVT by inhibiting spontaneous SR Ca2+ release as well as the Na+ channel [63]; however, its usefulness in electrical storms remains to be confirmed. If pharmacologic treatment fails to control the CPVT, left cardiac sympathetic denervation should be considered [52]. One recent case report has shown that RFCA targeting premature ventricular VF-triggering contractions was successful for controlling recurrent CPVTs refractory to beta-blocker therapy [64]. Idiopathic VF is a clinical entity in which no cardiac anatomic or functional abnormality can be identified despite extensive clinical evaluation for the cause of VF. Therefore, the pathophysiology of idiopathic VF must include multifactorial disorders of unknown origin. However, the similar clinical presentation of this entity indicates that these disorders share some common mechanisms. Leenhardt et al. [65] first described a group of patients consistent with the clinical picture of idiopathic VF, but they termed it “short-coupled variant of TdP.” The interesting characteristic observed in these patients is the unusually short coupling interval of the precipitating VF (245±28ms). Verapamil was the only effective drug, supporting the theory that the verapamil-sensitive ventricular myocardium might be involved in permitting triggered activity and VF. Antiarrhythmic drugs and beta-blockers are ineffective; in fact, class I antiarrhythmic drugs can be harmful [66]. It is notable that RFCA of triggered premature ventricular contractions that emanate from either Purkinje fibers or the ventricular myocardium, particularly in the right ventricular outflow tract, can be successful in suppressing and preventing electrical storms due to idiopathic VF [66,67]. These observations also indicate the important role of the Purkinje system in the genesis of idiopathic VF.
Polymorphic VT/VF storms in structural heart disease In the absence of a prolonged QT interval, the most common cause of polymorphic VT is myocardial ischemia. Indeed, the specific arrhythmia that arises from acute myocardial ischemia is almost always polymorphic VT/VF. Hence, polymorphic VT/VF storms in patients with coronary disease are strongly suggestive of acute myocardial ischemia. Myocardial ischemia leads to repetitive inductions of VT through various mechanisms, including abnormal automaticity with altered membrane potential, triggered activity, and phase 2 reentry. Revascularization procedures may be urgently needed for polymorphic VT/VF storms associated with myocardial ischemia. Sympathetic blockade with beta-blockers or left cardiac sympathetic denervation has been shown to result in a better outcome than class I antiarrhythmic drugs in patients with polymorphic VT/VF storms associated with recent myocardial infarction [6]. Nevertheless, antiarrhythmic drugs remain a useful adjunctive therapy for controlling polymorphic VT/VF storms in the presence of ischemia. In ischemic conditions, lidocaine is believed to be effective by its preferential binding to fast Na+ channels in ischemic myocytes, but intravenous amiodarone appears to be more effective than lidocaine and other antiarrhythmic drugs [68]. In some patients, polymorphic VT/VF still occurs despite revascularization and medical therapy. Purkinje fibers are relatively resistant to ischemia, as they are supplied by cavity blood and have higher glycogen levels and fewer myofibrils. Following myocardial infarction, surviving Purkinje fibers in ischemic lesions have increased SR Ca2+ leak and triggered activity [69]. RFCA aimed at the Purkinje potentials preceding the QRS onset of ventricular premature contractions that initiate polymorphic VT/VF can terminate and prevent electrical storms in patients with acute myocardial infarction [70] and ischemic cardiomyopathy [71]. During the acute phase of myocardial infarction, bradycardia-dependent polymorphic VT/VF can occur with marked QT prolongation [72]. In these cases, pharmacologic therapies and pacing are useful in the same manner as those used for acquired LQTS.