Citations

Background— Many ablative approaches in or near the orifice of the pulmonary vein (PV) have demonstrated success in eliminating atrial fibrillation. Despite current practice, there are no data regarding the in vivo efficacy and safety of an 8-mm catheter tip for ablation at the PV orifice. Methods and Results— Ten mongrel dogs were studied. Thermocouples were implanted in the atrial muscle of the PV orifice. Intracardiac echocardiography monitored catheter position, tip/tissue orientation, and microbubble formation. Ninety-four ablations were performed for 120 seconds. A temperature discrepancy >10°C between the catheter tip and tissue occurred during 47 (50%) of the ablations. Despite termination of energy delivery, the average tissue temperature remained within 1°C of the achieved steady state for 9 seconds. A temperature discrepancy >10°C was more common in the right superior PV, with oblique catheter positioning, when tissue temperatures were >60°C or 80°C, and with type 1 or type 2 microbubble formation. However, microbubbles were not present in 7 (13%, type 1) and 10 (40%, type 2) ablations with tissue temperatures >80°C. The maximum tissue temperature achieved with non–full-thickness lesions was 47.3±7.4°C vs 75.9±11.7°C ( P <0.0001) for full-thickness lesions. Conclusions— Marked discrepancies between catheter-tip and tissue temperatures occurred with higher temperatures, prolonged ablation times, and unfavorable catheter thermistor–tissue contact. Also, these data suggest a conservative approach to atrial ablation, because full-thickness lesions were obtained when tissue temperatures reached 50°C to 60°C and the tissue retained high heat levels despite termination of radiofrequency energy. Finally, microbubbles are inconsistent markers of tissue overheating.

AbstractAbnormalities of hemoglobin synthesis are usually inherited but may also arise as a secondary manifestation of another disease, most commonly hematologic neoplasia. Acquired hemoglobin disorders can be seen in any population and are not restricted to areas of the world with high incidences of inherited hemoglobinopathies. In fact, the acquired hemoglobinopathies may be more readily recognized where inherited hemoglobin abnormalities are rare and less likely to cause diagnostic confusion. Acquired α-thalassemia is the best characterized of the acquired red blood cell disorders in patients with hematologic malignancy, and it is almost always associated with a myelodysplastic syndrome (MDS). At least 2 molecular mechanisms for acquired α-thalassemia are now recognized: acquired deletion of the α-globin gene cluster limited to the neoplastic clone and, more commonly, inactivating somatic mutations of the trans-acting chromatin-associated factor ATRX, which cause dramatic down-regulation of α-globin gene expression. Here we review the clinical, hematologic, and molecular genetic features of α-thalassemia arising in a clonal myeloid disorder, and we discuss howATRX might affect gene expression in normal and abnormal hematopoiesis through epigenetic mechanisms.

Background— Preclinical systolic or diastolic dysfunction is associated with increased morbidity and mortality. We postulated that plasma brain natriuretic peptide (BNP) might serve as a biomarker for preclinical ventricular dysfunction (PCVD) but that the discriminatory values for BNP may vary with age and sex. Methods and Results— We measured BNP, systolic and diastolic ventricular function, and clinical parameters in 2042 randomly selected residents of Olmsted County, Minn, aged 45 years or older. For preclinical systolic dysfunction, the areas under the receiver operating characteristics curve were higher for those with more severe (0.82 to 0.92) than any (0.51 to 0.74) systolic dysfunction and were similar in men and women and in younger and older persons. For preclinical diastolic dysfunction, the areas under the receiver operating characteristics curve were higher for those with moderate-to-severe (0.74 to 0.79) than any (0.52 to 0.68) diastolic dysfunction and were similar regardless of age or sex. Optimal discriminatory values of BNP varied with age and sex. Considering the prevalence of preclinical systolic or diastolic dysfunction and the predictive characteristics observed, using BNP to screen for PCVD would necessitate echo in 10% to 40% of those screened, with most confirmatory echocardiograms being negative, and would miss 10% to 60% of those affected. Conclusions— BNP is a suboptimal screening test for PCVD in the population.