Biomedical subjects

Andrew T Ho

Publications and source records attributed to Andrew T Ho.

4 recordsLinked to original sources

PubMed2005

Increased P-wave dispersion predicts recurrent atrial fibrillation after cardioversion.

Atrial fibrillation (AF) will recur in a number of patients treated with cardioversion. Being able to identify reliable risk factors would be useful for making management decisions. P-wave dispersion (PWD) is an electrocardiographic measurement, which reflects a disparity in atrial conduction. P-wave dispersion has been shown to be increased in patients with paroxysmal AF. This pilot study aims to determine the role of PWD in predicting AF recurrence in patients who underwent elective cardioversion. Forty-five patients who were successfully cardioverted for persistent AF were included for study. Eighteen patients had a PWD greater than 80 ms; of these 13 had AF recurrence. Of the 25 patients with PWD less than 80 milliseconds, 12 had recurrent AF. P-wave dispersion values greater than 80 milliseconds were found more frequently in patients with AF recurrence (P = .05), supporting the use of this parameter in predicting return of AF. Larger studies are needed for further evaluation.

Aged↗

PubMed2005

Effect of concomitant antiarrhythmic therapy on survival in patients with implantable cardioverter defibrillators.

BACKGROUND: Application of implantable cardioverter defibrillator (ICD) therapy is expanding to include both primary and secondary prevention of sudden cardiac death and has been proven to be superior to conventional antiarrhythmic therapies. Concomitant antiarrhythmic drug therapy in patients with ICD is common. These drugs are potentially proarrhythmic, alter defibrillation thresholds, and may affect response to device therapy. However, the impact of concomitant antiarrhythmic drug therapy on survival in patients with ICD devices is unknown. METHODS: We investigated the effect of different antiarrhythmic drugs on survival when given concomitantly in 360 consecutive ICD patients from our university medical center. Mortality data were obtained from the national death index. Survival analysis was performed using the Kaplan-Meier method. Corrections for significant covariates and group differences were made using the Cox regression model. RESULTS: Patients were followed up for 4.4 +/- 3.7 years. There were 68 deaths over this period with a 5-year survival of 80%. Patient characteristics were: age 62 +/- 13 years, left ventricular (LV) ejection fraction (EF) 33 +/- 17%, ischemic etiology of LV dysfunction 68%, diabetes mellitus 19%, hypertension 49%, atrial fibrillation 23%, digoxin 43%, beta-blocker 46%, amiodarone 28%, and sotalol 9%. The use of beta-blockers was associated with a better survival (P = 0.0005). This effect persisted after correcting for age, heart rate, EF, and ischemic etiology. The beneficial effect of beta-blocker was unrelated to its effect on heart rate. Digoxin use was associated with a lower survival only on univariate analysis (P = 0.006), but not after adjusting for other variables on a Cox regression model (P = 0.093). Amiodarone and sotalol were found to have a neutral effect on survival. CONCLUSION: In patients with ICDs, beta-blockers had a favorable effect on survival. Sotalol and amiodarone had a neutral effect on survival. There was a trend toward a deleterious effect with digoxin use. These findings suggest a need for further investigation addressing survival effects of antiarrhythmic drugs when given concomitantly in patients with ICDs.

Adrenergic beta-Antagonists↗

PubMed2004

Splitting the apoptosome.

Assembly of the apoptosome in response to mitochondrial permeabilization, the hallmark of the intrinsic apoptotic pathway, involves binding of cytochrome c to Apaf1, recruitment and auto-processing of the apical/signaling pro-caspase-9, and coupled activation of downstream/executioner caspases like caspase 3. Evidence now indicates that certain apoptotic cascades can bypass the apoptosome and activate caspase-9 independent of the mitochondria. Recently, we have demonstrated that caspase-9 can be activated in Apaf1-mutant primary myoblasts, but not fibroblasts, in response to stimuli that are known to act via the mitochondria. Thus, apoptosomal activation of caspase-9 seems to represent only one of the routes for its activation; other pathways, some of which are yet to be discovered, can bypass the requirement for Apaf1 and activate caspase-9 in a tissue and context specific manner.

Animals↗

PubMed2004

Coupling of caspase-9 to Apaf1 in response to loss of pRb or cytotoxic drugs is cell-type-specific.

Inactivation of the tumor suppressor Rb in the mouse induces cell death, which depends entirely (in lens, CNS) and only partly (PNS, skeletal muscles) on Apaf1/Ced4, an apoptosomal factor thought to be required for processing procaspase-9 following mitochondrial permeabilization. Here, we report that in response to cytotoxic drugs, Apaf1(-/-) primary myoblasts but not fibroblasts undergo bona fide apoptosis. Cell demise was associated with disruption of mitochondria but not endoplasmic reticulum. Processing of procaspase-9 occurred in Apaf1(-/-) myoblasts but not fibroblasts, and ablation of Casp9 prevented drug-induced apoptosis in both cell types. Deregulation of the Rb pathway by overexpression of E2F1 also induced caspase-9-dependent, Apaf1-independent apoptosis in myoblasts. Despite its requirement for apoptosis in vitro, mutation in Casp9 abrogated cell death in the nervous system and lens but only partly in skeletal muscles of Rb-deficient embryos. In addition, developmental cell death in fetal liver and PNS was not inhibited in Casp9(-/-) embryos. Therefore, loss of pRb elicits apoptosome-dependent and apoptosome-independent cell death, and the requirement and coupling of caspase-9 to Apaf1 are both context-dependent.

Animals↗