Congenital Long Qt Syndromes example essay topic

Objectives The objectives of this case study are to evaluate the cause of death for a female patient that presented to the ER with ventricular tachycardia, of which elevated to ventricular fibrillation and was unsuccessfully resuscitated. Furthermore, what genetic presupposition to development of VT did she have, and how was this augmented by the influence of Seldane (R) (active ingredient), an over the counter anti-histamine allergy season remedy. Clinical History During spring time of 1998, a typically healthy 43 year old deaf woman presented in the ER with cardiac arrhythmia. Electrocardiogram (ECG) analysis showed a broad QRS segment, suggesting sustained ventricular tachycardia (VT). Due to the ECG analysis, chemical cardio conversion by lidocaine administration was attempted (a 100 mg IV was rapidly run for 2 minutes as standard initial procedure); however, rapid onset of ventricular fibrillation occurred. Direct current defibrillation was employed with a range of 200-300 joules, but unfortunately was unsuccessful.

Before a second attempt of defibrillation could be administered, the woman presented with syncope. CPR was attempted however was unsuccessful; briefly after was pronounced dead due to sudden cardiac death (SCD). Investigations Blood samples showed sodium (Na+), potassium (K+), and calcium (Ca 2+) imbalances, and high content of over the counter antihistamine active ingredient. After overview of the patient's medical history, it was confirmed that her deafness was of congenital nature (specifically neuro sensorial). Understanding that this feature is often linked to congenital long QT syndromes, genetic analysis was performed. Analysis found a point mutation in the KCNQ 1 and KCNE 1 genes (found on chromosome 11), of which she was homozygous recessive.

Discussion: Clinic-pathological Correlations The genetic findings on chromosome 11 specifically regarding genes KCNQ 1 and KCNE 1 definitively confirm that the women suffered from Jer vell-Lange-Nielsen syndrome (JLNS). JLNS is a congenital long QT syndrome with recessive associated deafness (Berkow, 492). The alterations in genes KCNQ 1 and KCNE 1 in most cases prolong the action potential time span (see Figure 1.0) by increasing inward depolarizing currents or decreasing outward currents during the plateau phase (Figure 2.0). Specifically for JLNS, the slow acting potassium transporter IKs shows a decrease in outward transportation of potassium during the phase of the cardiac action potential cycle. This decrease in transporter efficacy is directly related to the mutations in genes KCNQ 1 and KCNE 1 (Hugues A. et al. ).

Overall, this genetic predisposition to the development of ventricular arrhythmia due to the long QT is termed Torsade de Pointes; this is because although clinically the ECG looks similar to that of ventricular tachycardia, in this case the ECG shows a continuously changing QRS vector that is often sparked by the generation of one or two extrasystole occur ances (Figure 3.0) (Berkow 491). Risk factors for Torsade de Pointes include female gender, heart disease, , , , and most importantly drugs that prolong the QT interval. The increase risk in the female gender is believed to due in part to a decrease in potential because they produce less current within the heart (Hugues, A., et al). In this particular case, the involvement of is very important because it is a Histamine-1 receptor antagonist, which can cause cardiac arrhythmia's, thus predisposing patients with congenital long QT syndromes (in this case JLNS) to development of Torsade de Pointes (Rang H, et al., 242). Clinical use of H 1-receptor antagonists are mainly for control of allergic reactions, which explains the concentration of found in the patient based on the time of year. Specifically, interacts with three main areas that relate to cardio-control, they are as follows: a decrease in contraction of smooth muscle other than blood vessels, vasoconstriction of blood vessels, and a decrease in vascular permeability (Rang H, et al., 213).

These processes directly affect blood pressure and heart rate, thus predisposing someone taking to cardiac changes. Therefore, with the combination of the patient suffering from JLNS due to mutations in genes KCNQ 1 and KCNE 1, she was presupposed to development of Torsade de Pointes due to a decrease in IKs K+ channel activity. Female gender potentiated this risk because of a general decrease in cardiac potential, and lastly the administration of Seldane (R) to relieve her allergy symptoms caused the onset of the experienced VT due to the interaction of at histamine-1 receptors, ultimately leading to VF and sudden cardiac death.

Bibliography

Berkow R.A. Fletcher. The Merck Manual of Diagnosis and Therapy: 16th Ed. Rahway: NJ Merck Research Laboratories, Merck & Co., Inc., 1992.
Hugues A., et al. Molecular and clinical determinants of drug-induced long QT-syndrome: and iatrogenic. Swiss Med Wkly. 2004;
134: 685-694. Rang H., M. Dale, J. Ritter, P. Gardner. Pharmacology: 4th Ed. Philadelphia: Pennsylvania Churchill Livingstone, 2001.