Prognostic value of quantitative stress myocardial perfusion imaging in unstable angina patients with negative cardiac enzymes and no new ischemic ECG changes

Background. Limited data are available on the value of quantitative stress myocardial perfusion imaging (MPI) in patients with unstable angina. In this report we sought to study the long-term prognostic value of quantitative stress MPI in patients hospitalized with unstable angina with no new ischemic electrocardiographic changes and negative cardiac enzymes. Methods and Results. The study population consisted of 136 patients who were hospitalized at the Methodist Hospital, Houston, Tex, with unstable angina and subsequently underwent MPI before discharge. Cox proportional hazards (regression) analysis was performed to identify clinical and MPI predictors of hard cardiac events (death or nonfatal myocardial infarction). During a mean follow-up of 31 ± 17 months, 20 patients (15%) sustained either cardiac death (n = 12) or nonfatal myocardial infarction (n = 8). The significant multivariate predictors of cardiac events were the total perfusion defect size (P = .002), the presence of reversible perfusion defects (P = .01), and the presence of multiple perfusion defects (P = .03). The perfusion defect size was significantly larger in patients with events than in those without events (21% ±20% vs 12% ± 14%, P = .002). Kaplan-Meier analysis showed that cardiac events were much more likely to develop in patients with defects involving 15% or more of the left ventricle than in those with defects involving less than 15% of the left ventricle (P = .003). Conclusions. In patients hospitalized with unstable angina with no new ischemic electrocardiographic changes and negative cardiac enzymes, quantitative stress MPI provides powerful prognostic information that can be used in the risk stratification of these patients. (J Nucl Cardiol 2005;12:32-6.)     

Rate-dependent AV delay optimization in cardiac resynchronization therapy

BACKGROUND: During cardiac resynchronization therapy (CRT), cardiac performance is dependent on an optimized atrioventricular delay (AVD). However, the optimal AVD at different heart rates has not been defined yet during CRT. METHOD: The effects of an increase in heart rate by pacing or physical exercise on optimal AVD were studied in 36 patients with biventricular pacemakers/defibrillators. The velocity time integral (VTI) in the left ventricular outflow tract (LVOT) was measured with pulsed Doppler either at three different paced heart rates in the supine position or in seated position before and after physical exercise. RESULTS: The baseline AVD was optimized to 99 +/- 19 ms in the supine and 84 +/- 22 ms in the seated position. When the heart rate was increased by DDD pacing, there was a positive linear relationship between an increase in heart rate, in AVD and in VTI (LVOT-VTI + 0.047 cm/s per 10 beats per minute (bpm) heart rate increase per 20 ms increase in AVD, P = 0.007). A similar but more pronounced relationship was found after physical exercise in the seated position (LVOT-VTI + 0.146 cm/s per 10 bpm heart rate increase per 20 ms increase of AVD, P = 0.013). This effect was observed in patients with and without AV block and mitral regurgitation. CONCLUSIONS: In conclusion, the systolic performance of the dilated ventricle, which depends on an elevated preload, is critically affected by the appropriate timing of the AVD during exercise. In contrast to normal pacemaker patients, in CRT the relatively short baseline AVD should be prolonged at increased heart rates. Further studies with other means of measuring exercise cardiac performance are needed to confirm these unexpected findings.     

Altered gene expression profiles in nasal respiratory epithelium reflect stable versus acute childhood asthma

BACKGROUND: Asthma is the most common chronic disease of childhood and has a strong genetic component. OBJECTIVE: To identify gene expression signatures that reflect asthma-related processes and to determine whether these genes were similar or distinct between stable asthma and acute exacerbations in childhood, we profiled gene expression patterns in nasal respiratory epithelial cells. METHODS: Children who had stable asthma (asthma-S; n = 10) and children experiencing an asthma exacerbation (asthma-E; n = 10) were recruited along with nonatopic children without asthma (n = 10). RNA was prepared from nasal respiratory epithelial cells isolated from each child, initially analyzed as pooled samples from the 3 groups, and further validated by using microarrays and RT-PCR with individual patient samples. RESULTS: Distinct gene clusters were identifiable in individual and pooled asthma-S and asthma-E samples. Asthma-E samples demonstrated the strongest and most reproducible signatures, with 314 genes of 34,886 measured as present on the chip demonstrating induction or repression of greater than 2-fold with P < .05 in each of 4 individual samples. Asthma-S-regulated genes encompassed genes that overlapped with those of asthma-E but were fewer (166) and less consistent with respect to their behavior across the asthma-E patient samples. CONCLUSION: Exacerbated asthma status is readily distinguished based on the occurrence of strong gene expression signatures in nasal epithelial samples. Stable asthma status also exhibits differential signatures. The results suggest that there are independent gene expression signatures reflective of cells and genes poised or committed to activation by an asthma attack.     

Mitochondrially targeted vitamin E and vitamin E mitigate ethanol-mediated effects on cerebellar granule cell antioxidant defense systems

Ethanol (EtOH) disrupts the structure and function of the developing nervous system, sometimes leading to birth defects associated with fetal alcohol syndrome (FAS). Animal FAS models indicate that cellular membrane peroxidation, intracellular oxidant accumulation, and suppression of endogenous antioxidant enzymes contribute to the toxic effects of EtOH. Mitochondrially targeted vitamin E (MitoVit E), a chemically engineered form of vitamin E (VE) designed to accumulate in the mitochondria, has been shown to inhibit intracellular oxidant accumulation and cell death more effectively than VE. In previous investigations, we have shown that, in vivo, VE reduces neuronal death in the developing cerebellum of EtOH-exposed animals, and, in vitro, VE prevents apoptotic and necrotic death of EtOH-exposed cerebellar granule cells (CGCs). The present investigation shows that, in a FAS CGC model, 1 nM MitoVit E renders significant neuroprotection against EtOH concentrations as high as 1600 mg/dL. The present study also demonstrates that, in this same model, MitoVit E mitigates EtOH-induced accumulation of intracellular oxidants and counteracts suppression of glutathione peroxidase/glutathione reductase (GSH-Px/GSSG-R) functions, protein expression of gamma-glutamylcysteine synthetase (gamma-GCS), and total cellular glutathione (GSH) levels. In the presence and absence of EtOH, VE amplifies the protein expression levels of gamma-GCS, an enzyme that performs the rate-limiting step for GSH synthesis, and total GSH levels. These results suggest that MitoVit E and VE ameliorate EtOH toxicity through non-oxidant mechanisms-modulations of endogenous cellular proteins-and antioxidant means.     

Research knowledge among parents of children participating in a randomized clinical trial

OBJECTIVE: Parental permission is required for child research, but parents' understanding of research aims and procedures has not been well documented. Parental research knowledge was assessed during a clinical trial in autism. METHOD: Parents of 101 children (age 5-17 years) with autism participating in a placebo-controlled trial of risperidone were given a questionnaire at the end of the study. RESULTS: Of the 95 parents completing the questionnaire, 99% knew of possible placebo assignment and that testing the medication efficacy was the main purpose of the investigators; 96% to 98% knew that research involved both risks and potential benefits, identified the study medication, and knew of their right to withdraw at any time; 90% to 95% knew of the medication's main side effects; 87% reported having been informed of possible alternatives to research participation; and 72% were aware that treatment was randomly assigned (whereas 27% reported that treatment was chosen based on individual needs to ensure best care). Parents with a college degree were more likely to recognize the random nature of treatment assignment. CONCLUSIONS: Overall, parents were highly knowledgeable of the main research components. About one fourth, however, seemed unaware that treatment was randomly determined and not personalized, suggesting that therapeutic misconception may affect some otherwise well-informed parents.