Mutations in the cardiac ryanodine receptor Ca<sup>2+</sup> release channel (RyR2) can cause deadly ventricular arrhythmias and atrial fibrillation (AF).
Mutant RyR2 channels give rise to spontaneous release of calcium (Ca(2+)) from the SR during diastole, which enhances the probability of ventricular arrhythmias.
LMNAp.(Arg331Gln) carriers had a significantly better outcome regarding the composite end point (malignant ventricular arrhythmias, end-stage heart failure, or death) compared with carriers of other pathogenic <i>LMNA</i> mutations.
The aim of this study was to assess exercise test results and efficacy of therapy with a β blocker (acebutolol) in ryanodine receptor type 2 (RyR2) mutation carriers with documented ventricular arrhythmias (VAs) and long-term follow-up.
Mutations of the cardiac ryanodine receptor type 2 (RyR2) gene are known to cause effort-induced polymorphic ventricular arrhythmia, syncope and sudden death.
Desmosomal and LMNA gene variants identify the subset of DCM patients who are at greatest risk for SCD and life-threatening ventricular arrhythmias, regardless of the left ventricular ejection fraction.
In catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited disease characterized by stress-induced ventricular arrhythmias in young patients with structurally normal hearts, autosomal dominant mutations in RYR2 or recessive mutations in calsequestrin lead to aberrant diastolic Ca(2+) release from the SR causing arrhythmogenic delayed after depolarizations (DADs).
As abrupt sympathetic activation triggers ventricular arrhythmias that may cause syncopal attacks and sudden death in LQT1 patients, we investigated whether two known beta1-adrenergic receptor polymorphisms were associated with the duration of QT interval or history of symptoms in LQT1.
Dilated cardiomyopathy caused by lamin A/C gene (LMNA) mutation is complicated with atrioventricular (AV) conduction disturbances, malignant ventricular arrhythmias, and progressive severe heart failure.
More than 80 mutations in the skeletal RyR1 have been identified and linked to malignant hyperthermia, central core disease or multi-minicore disease, while more than 40 mutations in the cardiac RyR2 lead to ventricular arrhythmias and sudden cardiac death in patients with structurally normal hearts.
In conclusion, the A allele of rs3766871 in RYR2 not only associates with ventricular arrhythmias, but also serves as an independent predictor of sudden cardiac death, and the A allele of rs790896 in RYR2 is a protective factor against sudden cardiac death in patients with CHF.
This seems to be mainly attributable to a high prevalence of malignant ventricular arrhythmias and end-stage heart failure in LMNA and PLN mutation carriers.
Mutations in the lamin A/C gene (LMNA) may cause familial dilated cardiomyopathy (dilated cardiomyopathy) characterized by early onset atrio-ventricular block (A-V block) before the manifestation of dilated cardiomyopathy and high risk of sudden death due to ventricular arrhythmia, which is very similar to the phenotype of gap junction related heart disease.
We conclude that the LMNAR541C mutation should be considered not only in patients with malignant ventricular arrhythmia and LV local wall motion abnormalities, but also in classic dilated cardiomyopathy with profound segmental LV contractility defects.
A pooled analysis of available genotype-phenotype data shows a higher prevalence of sudden cardiac death (SCD), cardiac transplantation, or ventricular arrhythmias in LMNA and PLN mutation carriers compared to sarcomeric gene mutations.
Mutations in LMNA are variably expressed and may cause cardiomyopathy, atrioventricular block (AVB), or atrial arrhythmias (AAs) and ventricular arrhythmias (VA).
Atrial overdrive pacing completely prevented VA in 16 of 19 (84%) Casq2(-/-) and in 7 of 8 (88%) RyR2(R4496C/+) mice and significantly reduced ventricular premature beats in both CPVT models (P<0.05).