Carriage of Cytochrome 2C19 Polymorphism Is Associated With Risk of High Post-Treatment Platelet Reactivity on High Maintenance-Dose Clopidogrel of 150 mg/day Results of the ACCEL-DOUBLE (Accelerated Platelet Inhibition by a Double Dose of Clopidogrel According to Gene Polymorphism) Study

ObjectivesThis study sought to determine the impact of gene polymorphisms on platelet reactivity (PR) after clopidogrel 150 mg/day in patients treated with percutaneous coronary intervention (PCI).BackgroundAlthough high maintenance-dose (MD) clopidogrel reduces PR, it is unknown whether gene polymorphisms are related with the risk of high post-treatment PR (HPPR) after high-MD clopidogrel.MethodsWe included mostly patients receiving high-MD clopidogrel after PCI from previously registered Gyeongsang National University Hospital data. A total of 126 PCI-treated patients receiving high-MD clopidogrel were enrolled. Platelet reactivity was assessed with conventional aggregometry and VerifyNow (Accumetrics Inc., San Diego, California) after receiving clopidogrel 150 mg/day for at least 1 month. CYP3A5, CYP2C19, and ABCB1 genotyping was performed. We defined HPPR as 5 μmol/l adenosine diphosphate (ADP)–induced maximal PR (PRmax) >50%.ResultsCYP3A5 and ABCB1 polymorphisms did not influence PR. Carriers of CYP2C19 variant (*2 or *3) (n = 80) had significantly higher 5 and 20 μmol/l ADP-induced PRmax than did noncarriers (n = 46) (40.7 ± 16.8% vs. 30.3 ± 12.6%, p < 0.001; 54.2 ± 16.2% vs. 40.5 ± 15.8%, p < 0.001, respectively). Late PR and VerifyNow results indicated consistently greater measures in carriers versus noncarriers of CYP2C19 variant. All platelet measures proportionally increased according to the number of CYP2C19 variant alleles. Twenty-seven (21.4%) patients met the criteria for HPPR. Prevalence of HPPR was 8.7%, 21.7%, and 50.0% in carriers of 0, 1, and 2 CYP2C19 variant alleles, respectively (p < 0.001). By multivariate analysis, carriage of CYP2C19 variant was a significant predictor of HPPR (odds ratio: 5.525, 95% confidence interval: 1.333 to 23.256, p = 0.018).ConclusionsAmong PCI-treated patients receiving high-MD clopidogrel, carriage of CYP2C19 variant relates to increased PR and predicts risk of HPPR. (Adjunctive Cilostazol Versus High Maintenance-dose ClopidogrEL in Acute Myocardial Infarction [AMI] Patients According to CYP2C19 Polymorphism [ACCELAMI2C19]; NCT00915733; and Comparison of Platelet Inhibition With Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel According to Hepatic Cytochrome 2C19 Allele (CYP2C19) Polymorphism [ACCEL2C19]; NCT00891670)

A Case of Spontaneous Coronary Artery Dissection Healed by Medical Treatment: Serial Findings of Coronary Angiography, Intravascular Ultrasound and Multi-Detector Computed Tomography

Spontaneous coronary artery dissection (SCAD) is an uncommon cause of acute coronary syndrome which may be related to lethal condition. Although several modalities including medical therapy have been suggested, agreement on optimal treatment has not yet been determined. We describe a case of SCAD which was presented as ST-segment elevation myocardial infarction, and treated successfully with medical treatment. Coronary angiography, intravascular ultrasound and multi-detector computed tomography showed the serial changes of this disease entity

Implantable Cardioverter-Defibrillator Implantation in a Patient with Atrial Standstill

We report a 55-year-old female patient who presented with no P waves but with a wide QRS complex escape rhythm at 44 beats/min and prolonged QTc of 0.55 seconds on ECG. The patient had recurrence of ventricular fibrillations and loss of consciousness, and underwent defibrillation and cardiopulmonary resuscitation (CPR) several times because of cardiac arrest. The transthoracic echocardiography showed dilated cardiomyopathy and enlargement of both atria. The Doppler echocardiography documented the absence of A wave in the tricuspid and mitral valve flow. An electrophysiologic study demonstrated electrical inactivity in the right and left atria. Atrial pacing with maximum output did not capture the atria. These findings together with her electrocardiographic finding indicated atrial standstill. Sudden cardiac death was her first clinical manifestation of ventricular arrhythmia. The patient remained asymptomatic after receiving a single chamber implantable cardioverter-defibrillator (ICD) with VVI pacemaker function

Gram-Negative Bacterial Endotoxin LPS Induces NeuGc Loss through Ets1-Dependent Downregulation of Intestine-Specific pcmah Transcript in Porcine Intestinal Cells

N-glycolylneuraminic acid (NeuGc), a non-human sialic acid derivative synthesized by cytidine-5&prime;-monophospho-N-acetylneuraminic acid hydroxylase (CMAH), plays a crucial role in mediating infections by certain pathogens. Although it has been postulated that NeuGc biosynthesis and CMAH expression are downregulated during microbial infection, the underlying mechanisms remain unclear. The present study showed that exposure to lipopolysaccharide (LPS), a Gram-negative bacterial endotoxin, leads to loss of NeuGc biosynthesis in pig small intestinal I2I-2I cells. This LPS-induced NeuGc loss was accompanied by decreased CMAH transcript levels, especially intestine-specific 5&prime;pcmah-1. Furthermore, LPS suppressed the activity of the Pi promoter responsible for 5&prime;pcmah-1 by inhibiting DNA binding of Est1. These findings provide insight into the regulatory mechanisms of Neu5Gc biosynthesis during pathogenic infectious events, which may represent a host defense mechanism that protects the self against pathogenic bacterial infections even in non-sanitary environments