Considering Ranolazine as a Potential Treatment for K⁺ Channel Linked Short QT Syndrome

Therapeutic effects of a taurine-magnesium coordination compound on experimental models of type 2 short QT syndrome

“…To date, few studies have reported effective pharmacological treatments for SQT2. According to the latest report by Hancox et al [35] , ranolazine potentially has therapeutic value for the treatment of SQT2 and SQT3. However, Frommeyer et al [18] demonstrated that the predominant anti-arrhythmic mechanism of ranolazine was most likely the inhibition of the fast component of the outward delayed rectifier potassium current (I Kr ), which corresponded to SQT1.…”

Left ventricular noncompaction cardiomyopathy and short QT syndrome due to primary carnitine deficiency

“…Long‐chain fatty acids (LCFAs) are important energy substrates in muscular tissue, but they are unable to diffuse freely across the inner mitochondrial membrane. L‐carnitine is a key metabolic cofactor, driving carnitine palmitoyltransferase I, a rate‐limiting step in mitochondrial uptake and oxidation of LCFAs (Fu et al, 2013; Hancox, 2018). Organic cation transporter 2 (OCTN2), encoded by the SLC22A5 gene (OMIM 603377) (Fu et al, 2013), is responsible for the active uptake of L‐carnitine into several tissues, in particular the heart, skeletal muscle, and kidney.…”

“…Mutations in the SLC22A5 gene cause primary carnitine deficiency (PCD; OMIM 212140), a rare autosomal recessive condition. Primary carnitine deficiency is characterized by deficiency in intracellular carnitine, low plasma carnitine, and high urinary carnitine due to renal wasting (Fu et al, 2013; Hancox, 2018). Primary carnitine deficiency commonly manifests in cardiac dysfunction, with the development of a progressive cardiomyopathy that can lead to end‐stage heart failure unless the condition is diagnosed and treated with carnitine supplementation (Fu et al, 2013; Shibbani et al, 2014).…”

“…Long-chain fatty acids (LCFAs) are important energy substrates in muscular tissue, but they are unable to diffuse freely across the inner mitochondrial membrane. L-carnitine is a key metabolic cofactor, driving carnitine palmitoyltransferase I, a rate-limiting step in mitochondrial uptake and oxidation of LCFAs (Fu et al, 2013;Hancox, 2018).…”

Considering Ranolazine as a Potential Treatment for K+ Channel Linked Short QT Syndrome

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We thank Dr. Hancox for his inspiring letter. 1 In the present study, short QT syndrome (SQTS) was simulated by treatment with the K-ATP channel activator pinacidil leading to an abbreviation of action potential duration, QTinterval, and effective refractory period. 2 These effects were reversed by treatment with either ranolazine (10 µM) or vernakalant (10 µM).

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