A Novel Frameshift Mutation, KCNH2 [p.Asp896ArgfsX79], Leading to Malignant Ventricular Arrhythmia, Identified After Treatment of Gastrointestinal Bleeding.

A novel frameshift mutation in the KCNH2 gene for long QT syndrome type 2 (LQTS2) was identified after torsades des pointes ventricular tachycardia in a 49-year-old patient managed with octreotide and nadolol for an acute variceal bleed. In spite of removal of offending medications, and correction of underlying electrolyte abnormalities, the patient's QT interval remained prolonged-at 521 ms-raising the suspicion of an underlying channelopathy. Genetic studies confirmed heterozygosity for a novel frameshift mutation for the KCNH2 gene, D896Rfs X79. We explore the pathogenicity and clinical impact of this variant mutation.

Une nouvelle mutation de changement de phase du gène KCNH2 impliqué dans le syndrome du QT long de type 2 (SQTL2) a été trouvée après une tachycardie ventriculaire à torsades de pointes chez un patient de 49 ans traité par octréotide et nadolol en raison d'un saignement variqueux en phase aiguë. En dépit du retrait des médicaments mis en cause et de la correction des anomalies électrolytiques sous-jacentes, l'intervalle du QT du patient qui demeurait prolongé (à 521 ms) a suscité la suspicion d'une canalopathie sous-jacente. Des études génétiques ont permis de confirmer l'hétérozygosité d'une nouvelle mutation de changement de phase du gène KCNH2, D896Rfs X79. Nous examinons la pathogénicité et les répercussions cliniques de cette mutation du variant.

ALCAPA and ASD Secundum Unmasked by Severe Postpartum Haemorrhage Complicated by Heart Failure.

Abnormal Left Coronary Artery from Pulmonary Artery (ALCAPA) is a rare congenital coronary anomaly in which the left main coronary artery arises from the pulmonary trunk, resulting in a left to right shunt. ALCAPA is associated with septal defects and patent ductus arteriosus. The case discussed had a secundum atrial septal defect. Sudden cardiac death is a feared complication. We discuss the hemodynamics of this shunt combination and outline its management, emphasizing shunt hemodynamics during pregnancy. This case highlights that pregnant patients with ALCAPA are at high risk and require optimal peri- and postpartum care. After surgical establishment of dual coronary circulation, patients have carried subsequent pregnancies to term.

L'ALCAPA est une anomalie coronarienne congénitale rare caractérisée par la naissance de l'artère coronaire gauche du tronc pulmonaire, qui entraîne un shunt gauche-droit. L'ALCAPA est associée à des malformations septales et une persistance du canal artériel. Le cas sur lequel nous nous sommes penchés avait une communication interauriculaire (CIA) de type ostium secundum. La mort subite d'origine cardiaque est la complication redoutée. Nous nous penchons sur l'hémodynamique de la combinaison de ce shunt et décrivons sa prise en charge, notamment celle de l'hémodynamique du shunt au cours de la grossesse. Ce cas illustre que les patientes enceintes qui ont une ALCAPA sont exposées à un risque élevé et qu'elles ont besoin de soins optimaux avant et après l'accouchement. Après l'établissement chirurgical de la circulation coronarienne double, les patientes ont mené à terme les grossesses subséquentes.

Takotsubo syndrome unmasking malignant coronary artery anomaly in a patient presenting with acute coronary syndrome: Expanding definitions of Takotsubo cardiomyopathy?

The simultaneous occurrence of Takotsubo syndrome, congenital coronary artery anomaly and severe coronary artery disease is a rare clinical triad. This case report highlights the intricacies of management of this 'triple jeopardy' scenario.

Protein phosphatase role in adenosine A1 receptor-induced AMPA receptor trafficking and rat hippocampal neuronal damage in hypoxia/reperfusion injury.

Adenosine signaling via A1 receptor (A1R) and A2A receptor (A2AR) has shown promise in revealing potential targets for neuroprotection in cerebral ischemia. We recently showed a novel mechanism by which A1R activation with N(6)-cyclopentyl adenosine (CPA) induced GluA1 and GluA2 AMPA receptor (AMPAR) endocytosis and adenosine-induced persistent synaptic depression (APSD) in rat hippocampus. This study further investigates the mechanism of A1R-mediated AMPAR internalization and hippocampal slice neuronal damage through activation of protein phosphatase 1 (PP1), 2A (PP2A), and 2B (PP2B) using electrophysiological, biochemical and imaging techniques. Following prolonged A1R activation, GluA2 internalization was selectively blocked by PP2A inhibitors (okadaic acid and fostriecin), whereas inhibitors of PP2A, PP1 (tautomycetin), and PP2B (FK506) all prevented GluA1 internalization. Additionally, GluA1 phosphorylation at Ser831 and Ser845 was reduced after prolonged A1R activation in hippocampal slices. PP2A inhibitors nullified A1R-mediated downregulation of pSer845-GluA1, while PP1 and PP2B inhibitors prevented pSer831-GluA1 downregulation. Each protein phosphatase inhibitor also blunted CPA-induced synaptic depression and APSD. We then tested whether A1R-mediated changes in AMPAR trafficking and APSD contribute to hypoxia-induced neuronal injury. Hypoxia (20 min) induced A1R-mediated internalization of both AMPAR subunits, and subsequent normoxic reperfusion (45 min) increased GluA1 but persistently reduced GluA2 surface expression. Neuronal damage after hypoxia-reperfusion injury was significantly blunted by pre-incubation with the above protein phosphatase inhibitors. Together, these data suggest that A1R-mediated protein phosphatase activation causes persistent synaptic depression by downregulating GluA2-containing AMPARs; this previously undefined role of A1R stimulation in hippocampal neuronal damage represents a novel therapeutic target in cerebral ischemic damage.