The advancement of studies about the molecular biology and electronic physiology on sudden cardiac death was summarized in this article, including particularly cardiac concussion(commotio cordis), congenital long QT syndrome, and Brugada syndrome which probably resulting in fatal arrhythmia and sudden cardiac death. These corpses of fatal functional disorders often show the results of negative autopsy without obvious organic pathological changes. So when come across negative autopsy the medical examiner and the pathologist should be careful to investigate the inductive cause of sudden death, the history of disease, and the family history, then to rule out the possibility of the above disorders.
Arrhythmias, Cardiac/pathology* ; Death, Sudden, Cardiac/pathology* ; Forensic Medicine ; Heart Injuries/pathology* ; Humans ; Long QT Syndrome/pathology*

BACKGROUNDVentricular tachycardia (VT) and ventricular fibrillation are the main reasons causing sudden cardiac death. This study aimed to investigate the effects of nifekalant hydrochloride (NIF) on QT dispersion (QTd) in treating VT.

METHODSA total of 16 consecutive patients suffered sustained VT was included and then randomly divided into two groups according to the administration duration of NIF. In long-time group (group L), patients were injected with NIF continuously for at least 12 hours after a bolus dose. The patients in short-time group (group S) were injected with NIF just for 1 hour.

RESULTSThere were 7 of all 10 episodes of VT which were terminated by NIF, including 4 episodes in group L were stopped over 1 hour after continuous infusion of NIF. One patient suffered from torsade de pointes. Electrocardiography analysis indicated that QTd was significantly decreased 12 hours after stopping of infusing NIF compared with that when VT stopped ((45.4 +/- 22.1) ms vs. (73.4 +/- 33.2) ms, P < 0.01), and the corrected QTd (QTcd) decreased too ((47.8 +/- 22.9) ms vs. (78.3 +/- 36.5) ms, P < 0.01). There was a positive correlation between the increase in QTd and dose of administrating NIF (P < 0.01), so was QTcd (P < 0.01).

CONCLUSIONSMore administration of NIF indicates higher terminating rate of VT and more QTd prolongation. However, the safety is acceptable if several important issues were noticed in using NIF, such as serum potassium concentration, stopping side-effect related agents, and carefully observing clinical responses.

Adult ; Anti-Arrhythmia Agents ; therapeutic use ; Electrocardiography ; Female ; Humans ; Long QT Syndrome ; drug therapy ; pathology ; Male ; Middle Aged ; Pyrimidinones ; therapeutic use ; Tachycardia, Ventricular ; drug therapy ; pathology ; Treatment Outcome

Sudden cardiac death accounts for majority of deaths in human. Evident cardiac lesions that may explain the cause of death can be detected in comprehensive postmortem investigation in most sudden cardiac death. However, no cardiac morphological abnormality is found in a considerable number of cases although the death is highly suspected from cardiac anomaly. With the advances in the modern molecular biology techniques, it has been discovered that many of these sudden deaths are caused by congenital ion channelopathies in myocardial cell, i.e., Brugada syndrome, long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and short QT syndrome, etc. This article presents the molecular genetics, electrocardiographic abnormalities, clinical manifestations, and mechanisms leading to sudden cardiac death with emphasis on the role of postmortem genetic testing in certification of cause of death. It may provide helpful information in investigating sudden cardiac death due to ion channelopathies in medico-legal practice.
Arrhythmias, Cardiac/genetics* ; Autopsy/methods* ; Brugada Syndrome/genetics* ; Cause of Death ; Channelopathies/genetics* ; Death, Sudden, Cardiac/pathology* ; Electrocardiography ; Forensic Pathology ; Genetic Testing ; Heart Conduction System/physiopathology* ; Humans ; Ion Channels/genetics* ; Long QT Syndrome/genetics* ; Mutation ; Tachycardia, Ventricular/genetics*

Arrhythmias, Cardiac ; diagnosis ; genetics ; pathology ; Brugada Syndrome ; diagnosis ; genetics ; pathology ; Channelopathies ; diagnosis ; genetics ; pathology ; DNA Mutational Analysis ; Electrocardiography ; Genetic Testing ; Heart Conduction System ; physiopathology ; Humans ; Infant ; Long QT Syndrome ; diagnosis ; genetics ; pathology ; Muscle Proteins ; genetics ; Mutation ; NAV1.5 Voltage-Gated Sodium Channel ; genetics ; Sodium Channels ; genetics ; Sudden Infant Death ; etiology

The long QT syndrome (LQTS) is a rare hereditary disorder in which affected individuals have a possibility of ventricular tachyarrhythmia and sudden cardiac death. We investigated 62 LQTS (QTc > or = 0.47 sec) and 19 family members whose genetic study revealed mutation of LQT gene. In the proband group, the modes of presentation were ECG abnormality (38.7%), aborted cardiac arrest (24.2%), and syncope or seizure (19.4%). Median age of initial symptom development was 10.5 yr. Genetic studies were performed in 61; and mutations were found in 40 cases (KCNQ1 in 19, KCNH2 in 10, SCN5A in 7, KCNJ2 in 3, and CACNA1C in 1). In the family group, the penetrance of LQT gene mutation was 57.9%. QTc was longer as patients had the history of syncope (P = 0.001), ventricular tachycardia (P = 0.017) and aborted arrest (P = 0.010). QTc longer than 0.508 sec could be a cut-off value for major cardiac events (sensitivity 0.806, specificity 0.600). Beta-blocker was frequently applied for treatment and had significant effects on reducing QTc (P = 0.007). Implantable cardioverter defibrillators were applied in 6 patients. Congenital LQTS is a potentially lethal disease. It shows various genetic mutations with low penetrance in Korean patients.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/genetics ; Calcium Channels/genetics ; Child ; Child, Preschool ; Electrocardiography ; Heart Arrest/genetics/pathology ; Humans ; Infant ; KCNQ1 Potassium Channel/genetics ; KCNQ2 Potassium Channel/genetics ; Long QT Syndrome/*diagnosis/*genetics ; Middle Aged ; Mutation/*genetics ; NAV1.5 Voltage-Gated Sodium Channel/genetics ; Penetrance ; Potassium Channels, Inwardly Rectifying/genetics ; Republic of Korea ; Risk Factors ; Seizures/genetics/pathology ; Young Adult

BACKGROUNDCongenital long QT syndrome (LQTS) is an ion channelopathy associated with genetic mutations. It is well known that most LQTS patients (91%) have a single mutation. The purpose of this study was to investigate the clinical characteristics of congenital LQTS patients with bigenic mutations in Taiwan, China.

METHODSCongenital LQTS patients were recruited consecutively at Taiwan University Hospital in Taiwan from 2003 to 2009. The diagnosis of LQTS was defined by an LQTS Schwartz score greater than 4. Mutation screening in KCNQ1, KCNH2, KCNE1, and SCN5A was performed using direct sequencing.

RESULTSThree of 16 LQTS patients (18.7%) were identified with bigenic mutations. One patient had missense mutations in KCNQ1 and KCNH2, the second in KCNQ1 and KCNE1, and the third in KCNH2 and SCN5A. The mean age at onset of LQTS for patients with bigenic mutations was (17 ± 3) years, and all of these patients were female. Two of them experienced seizure and one presented with syncope, although one of them had a family history of syncope. The mean QTc interval was (515 ± 17) ms, similar to those with single mutation or SNPs ((536 ± 74) ms, P = 0.63). Compared to those LQTS patients with single mutation or SNPs, a significantly higher percentage of LQTS patients with bigenic mutations presented with seizure and were younger at onset of the first index event (P = 0.03 and 0.001, respectively), but lower percentage of them presented with sudden cardiac death (P = 0.03).

CONCLUSIONSAlthough the percentage of bigenic mutations in LQTS is less than 10% in Caucasian populations, we identified 3 of 16 LQTS patients (18.7%, 95% confidence interval: 0.04-0.46) with bigenic mutations in Taiwan. However, the severity of their clinical presentations was not higher than those patients with single mutation or SNPs.

Adolescent ; Adult ; Aged ; ERG1 Potassium Channel ; Ether-A-Go-Go Potassium Channels ; genetics ; Female ; Genotype ; Humans ; KCNQ1 Potassium Channel ; genetics ; Long QT Syndrome ; genetics ; pathology ; Male ; Middle Aged ; Mutation ; NAV1.5 Voltage-Gated Sodium Channel ; genetics ; Polymorphism, Single Nucleotide ; genetics ; Potassium Channels, Voltage-Gated ; genetics ; Young Adult