Dilated Cardiomyopathy Phenotype-Associated Left Ventricular Noncompaction and Congenital Long QT Syndrome Type-2 in Infants With KCNH2 Gene Mutation: Anesthetic Considerations

Maddali, Madan Mohan; Thomas, Eapen; Al-Abri, Ismail Abdullah; Patel, Malay; Al-Maskari, Salim Nasser; Al-Yamani, Mohammed I

doi:10.1053/j.jvca.2022.05.016

Cited by 2 publications

(1 citation statement)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, several publications from Oman regarding channelopathies highlighted the prevalence and management strategies available in the country. 20,21 These reports suggest that cardiovascular etiologies may contribute to many of the SCD cases. The authors hope that the current study may provide an impetus for focused studies investigating the causes and inheritance pattern of cardiovascular etiologies especially premature atherosclerotic coronary artery disease, cardiomyopathies and channelopathies, which ultimately will influence the management, family screening, including genetic counseling.…”

Section: Discussionmentioning

confidence: 99%

Sudden Cardiac Death in Patients Under 49 Years Including Adolescents

Maddali,

Al Habsi,

Al Dhamri

et al. 2023

Sultan Qaboos Univ Med J

View full text Add to dashboard Cite

Objectives: This study aimed to identify the incidence of sudden cardiac death (SCD0 in adult patients under the age of 49 years, including adolescents with an out-of-hospital cardiac arrest that presented to the emergency department of a tertiary care hospital. Methods: This retrospective cross-sectional study was conducted at the Royal Hospital, Muscat, Oman, between January 2015 and December 2019. All patients with out-of-hospital cardiac arrest were enrolled. The incidence of SCD was evaluated. Information about the patient's demographic data, the site of cardiac arrest, the mode of arrival, the duration of pre-arrest symptoms and if cardiopulmonary resuscitation was performed was gathered. Survival data at 3-year follow-up was obtained. Results: A total of 117 out of 769 (15%) patients met the criteria for SCD. Male gender was predominant, with a median age of 33 years. In about 79.5% of the patients, cardiac arrest was witnessed. Only 43 patients (36.8%) received cardiopulmonary resuscitation at the arrest site; 21 patients (17.9%) had a shockable rhythm and 96 patients (82.1%) had a non-shockable rhythm. Spontaneous circulation was returned in 15 patients (12.8%). Nine patients (7.7%) were discharged from the hospital and 8 (6.8%) survived at least 36 months. Conclusion: The study findings indicate the prevalence of SCD among patients who experienced a cardiac arrest outside the hospital. Unfortunately, only a small number of patients were able to survive in the long term. By implementing preemptive screening for individuals and their families, it may be possible to prevent SCD and improve outcomes for those affected. Keywords: Death, Sudden, Cardiac; Epidemiology; Etiology; Risk Factors; Incidence; Cardiopulmonary Resuscitation; Retrospective Studies; Oman.

show abstract

Section: Discussionmentioning

confidence: 99%

Sudden Cardiac Death in Patients Under 49 Years Including Adolescents

Maddali,

Al Habsi,

Al Dhamri

et al. 2023

Sultan Qaboos Univ Med J

View full text Add to dashboard Cite

show abstract

Functional Characterization of the A414G Loss-of-Function Mutation in HCN4 Associated with Sinus Bradycardia

Verkerk

Wilders

2023

Cardiogenetics

View full text Add to dashboard Cite

Patients carrying the heterozygous A414G mutation in the HCN4 gene, which encodes the HCN4 protein, demonstrate moderate to severe bradycardia of the heart. Tetramers of HCN4 subunits compose the ion channels in the sinus node that carry the hyperpolarization-activated ‘funny’ current (If), also named the ‘pacemaker current’. If plays an essential modulating role in sinus node pacemaker activity. To assess the mechanism by which the A414G mutation results in sinus bradycardia, we first performed voltage clamp measurements on wild-type (WT) and heterozygous mutant HCN4 channels expressed in Chinese hamster ovary (CHO) cells. These experiments were performed at physiological temperature using the amphotericin-perforated patch-clamp technique. Next, we applied the experimentally observed mutation-induced changes in the HCN4 current of the CHO cells to If of the single human sinus node cell model developed by Fabbri and coworkers. The half-maximal activation voltage V1/2 of the heterozygous mutant HCN4 current was 19.9 mV more negative than that of the WT HCN4 current (p < 0.001). In addition, the voltage dependence of the heterozygous mutant HCN4 current (de)activation time constant showed a −11.9 mV shift (p < 0.001) compared to the WT HCN4 current. The fully-activated current density, the slope factor of the activation curve, and the reversal potential were not significantly affected by the heterozygous A414G mutation. In the human sinus node computer model, the cycle length was substantially increased, almost entirely due to the shift in the voltage dependence of steady-state activation, and this increase was more prominent under vagal tone. The introduction of a passive atrial load into the model sinus node cell further reduced the beating rate, demonstrating that the bradycardia of the sinus node was even more pronounced by interactions between the sinus node and atria. In conclusion, the experimentally identified A414G-induced changes in If can explain the clinically observed sinus bradycardia in patients carrying the A414G HCN4 gene mutation.

show abstract

Dilated Cardiomyopathy Phenotype-Associated Left Ventricular Noncompaction and Congenital Long QT Syndrome Type-2 in Infants With KCNH2 Gene Mutation: Anesthetic Considerations

Cited by 2 publications

References 26 publications

Sudden Cardiac Death in Patients Under 49 Years Including Adolescents

Sudden Cardiac Death in Patients Under 49 Years Including Adolescents

Functional Characterization of the A414G Loss-of-Function Mutation in HCN4 Associated with Sinus Bradycardia

Contact Info

Product

Resources

About