Mutation-linked, excessively tight interaction between the calmodulin binding domain and the C-terminal domain of the cardiac ryanodine receptor as a novel cause of catecholaminergic polymorphic ventricular tachycardia.

Background: Ryanodine receptor (RyR2) is known to be a causal gene of catecholaminergic polymorphic ventricular tachycardia (CPVT), an important inherited disease. Some of the human CPVT-associated mutations have been found in a domain (4026-4172) that has EF hand motifs, the so-called calmodulin (CaM)-like domain (CaMLD).

Objective: The purpose of this study was to investigate the underlying mechanism by which CPVT is induced by a mutation at CaMLD.

Correction of impaired calmodulin binding to RyR2 as a novel therapy for lethal arrhythmia in the pressure-overloaded heart failure.

Background: Calmodulin (CaM) is a key modulator of the channel gating function of the ryanodine receptor (RyR).

Objective: The purpose of this study was to investigate the pathogenic role of RyR-bound CaM in diastolic Ca leakage from the sarcoplasmic reticulum and arrhythmogenesis in pressure-overloaded heart failure.

Methods: Pressure overload was induced in 12-week-old mice by transverse aortic constriction (TAC) using a 27-gauge needle.

Transcatheter and percutaneous procedures for huge pelvic arteriovenous malformations causing high-output heart failure.

We present the case of a 63-year-old woman presenting with a huge pelvic and retroperitoneal high flow arteriovenous malformation (AVM) causing high-output heart failure, who was treated with combined therapies, including transarterial embolization with n-butyl cyanoacrylate-iodized oil mixture (NBCA-lip) and coils for the right ovarian, both internal iliac, 3rd and 4th lumber arteries, venous sclerotherapy using coils and ethanolamine oleate (EO) for the right ovarian and both internal iliac veins with balloon-occluded retrograde transvenous obliteration technique, and direct percutaneous sclerotherapy using the NBCA-lip and EO for the large nidus of AVM under outflow control using occlusion balloon catheters. < Huge arteriovenous fistulae or malformation (AVF/M) are potentially life threatening due to the potential for spontaneous hemorrhaging and high-output heart failure and are notoriously difficult to diagnose and treat. To improve the high-output heart failure, intensive and invasive combined treatments for huge AVF/M are needed including transarterial and transvenous embolization and sclerotherapy and percutaneous nidus sclerotherapy.