There are healthy and young people out there who have suddenly died unexpectedly with no pathological signs or symptoms to explain their sudden deaths. With these cases, the only clinical manifestation in 50% of them is sudden unexplained death (SUD). In research, studies have demonstrated the suggestion that there are arrhythmogenic disorders with an example of congenital long QT syndrome, syndrome of the Brugada, ventricular fibrillation that is idiopathic being the underlying cause and reason behind many sudden unexplained death cases. In instances of arrhythmogenic cardiac disorders, pathological inconsistencies are not present or evidenced in the heart post-mortem, and the cause of death has an unknown aetiology upon examination.
The Mayo clinic proceedings current issue presented with molecular genetic analysis, cardiac ryanodine receptor gene mutations that can be related to 14% of sudden unexplained death cases. These mutations used to be thought of as linked to catecholaminergic polymorphic ventricular tachycardia (CPVT). Also, mutations in the gen known as calsequestrin have been linked to a recessive shape of CPVT. CPVT isn’t defined by heart disease that is structural in nature. CPVT can be characterized by electrococardiographic patters that are normal at rest and it is argued to be one of the most common types of malignant inherited cardiac arrhythmia syndromes.
It is thought that exercise and/or activation of the sympathetic nervous system will bring about ventricular arrhythimias, sudden cardiac death or syncope in individuals who have CPVT. This has led to a mortality rate of about 30% to 50% in individual’s ages around 35 years old. Some research findings have also demonstrated a suggestion that catecholamines are involved in the onset of arrhythmias that are lethal in nature, with 3 of 7 patients dying during physical exertion and one dying from emotional stresses.
Clinical studies have shown support for the theory that beta blockers can prevent cardiac episodes occurring in patients with CPVT. This is consistent with the idea that the sympathetic nervous system activation and mutation of certain genes can be preventable. The results currently shown are promising but there have been cases of sudden cardiac death occurring in small groups of patients with CPVT. It’s also important to note that beta blockers may seem to prevent most cardiac events but they don’t abolish the arrhythmias usually, which can be still brought about at rates higher of the heart. With these cases it is prudent to consider implanting a cardioverter defibrillator.
There are specific clinical therapies currently being developed to use in treatment of CPVT, specifically the molecular defect underlying this condition, so that adverse effects related to beta adrenergic receptor blockage is limited.
During a scenario whereby exercise is initiated or an individual is experiencing stress that activates the sympathetic nervous system, it will result in a protein kinase A phosphorylation that removes the association of the inhibitory factor subunit known as calstabin2 from the channel complex and thus increase calcium produced activation of cardiac ryanodine receptor genes. However, with the protein kinase A phosphorylation, the mutated cardiac ryanodine receptor genes demonstrate a significant spike in activity, which suggests that there may be more channels that are active than any wild type channel during exercise, as they show more calcium dependent activation in low intracellular calcium concentrations. This leads to the presentation that it can be suggested that calcium ions are possibly leaking from the reticulum of the sarcoplasma, which may play an essential part in the skeletal muscle and cardiac disease pathogenesis being related to cardiac ryanodine receptor genes.
With most arrhythmogenc cardiac conditions that lead to sudden death, CPVT is an autosomal dominant trait that is inherited from 50% of offspring from individuals who have a chance of developing with the same condition. The presence of CPVT in individuals should in most circumstances be excluded from most if not all cases of sudden unexplained death, whereby the post mortem examination presents negatively for histopathological or anatomical evidence. Congenital long QT syndrome is another condition that plays a role in about 10% to 15% of sudden unexplained death cases, and it presents with signs and symptoms that are similar. Diagnosing congenital arrhythmogenic conditions with an autopsy can help gather a screening of clinically of family members who have survived. Thus, family screening with counselling is essential in preventive therapies for sudden cardiac death cases.
© Copyright 2016 Michael Lam, M.D. All Rights Reserved.
