First inappropriate implantable cardioverter defibrillator therapy is often due to inaccurate device programming: analysis of the French OPERA registry

AIMS: Inappropriate therapy delivered by implantable cardioverter defibrillators (ICDs) remains a challenge. The OPERA registry measured the times to, and studied the determinants of, first appropriate (FAT) and inappropriate (FIT) therapies delivered by single-, dual- and triple-chamber [cardiac resynchronization therapy defibrillator (CRT-D)] ICD. METHODS AND RESULTS: We entered 636 patients (mean age = 62.0 ± 13.5 years; 88% men) in the registry, of whom 251 received single-, 238 dual-, and 147 triple-chamber ICD, for primary (30.5%) or secondary (69.5%) indications. We measured times to FAT and FIT as a function of multiple clinical characteristics, examined the effects of various algorithm components on the likelihood of FAT and FIT delivery, and searched for predictors of FAT and FIT. Over 22.8 ± 8.8 months of observation, 184 patients (28.9%) received FAT and 70 (11.0%) received FIT. Ventricular tachycardia (VT) was the trigger of 88% of FAT, and supraventricular tachycardia was the trigger of 91% of FIT. The median times to FIT (90 days; range 49-258) and FAT (171 days; 50-363) were similar. The rate of FAT was higher (P <0.001) in patients treated for secondary than primary indications, while that of FIT were similar in both groups. Out of 57 analysable FIT, 27 (47.4%) could have been prevented by fine tuning the device programming like the sustained rate duration or the VT discrimination algorithm. CONCLUSIONS: First inappropriate therapy occurred in 11% of 636 ICD recipients followed for ～2 years. Nearly 50% of FIT could have been prevented by improving device programming.     

Modulation of in vitro eosinophil progenitors by hydrocortisone: role of accessory cells and interleukins

The growth of human eosinophil progenitors (CFU-Eo) and the modulation of growth by hydrocortisone were studied as functions of the presence of lymphocytes and monocytes in marrow cells under study; and the source of colony-stimulating factors, specifically, media conditioned by macrophage-like cell line, GCT; phytohemagglutinin-stimulated mononuclear cells (PHA-LCM); or the T cell line, MO. CFU-Eo growth was greatest in marrow containing accessory cells as compared to marrow depleted of accessory cells; and in marrow treated with phytohemagglutinin-stimulated leukocyte conditioned media (PHA-LCM) or MO (T cell line)-conditioned medium (MO-CM) as compared with GCT cell- conditioned medium (GCT-CM). Hydrocortisone reproducibly inhibited eosinophil progenitor growth in unfractionated marrow stimulated by GCT- CM. This effect was abrogated by admixing irradiated mononuclear cells or T lymphocytes with the target marrow or by adding interleukin 1 or interleukin 2 (IL-1, IL-2). Inhibition by hydrocortisone did not occur when monocyte and T lymphocyte depleted marrow was studied. Unlike GCT- CM, MO-CM and PHA-LCM stimulated equal proportions of eosinophil progenitors in nondepleted and accessory cell-depleted marrow and demonstrated less hydrocortisone inhibition. However, both GCT-CM and PHA-LCM produced in the presence of hydrocortisone stimulated significantly fewer CFU-Eos in both unfractionated and accessory cell- depleted marrow target populations. These results indicate that the growth of CFU-Eo and inhibition of growth by hydrocortisone is a direct function of a monocyte-T cell interaction and probably is mediated through effects on the production/release of eosinophil colony stimulating factor (Eo-CSF).     

Acute effect of smoking on the functional activity of alpha1-protease inhibitor in bronchoalveolar lavage fluid

To assess the acute effect of smoking on the functional activity of alpha1-protease inhibitor (alpha-Pl) in bronchoalveolar lavage (BAL), we studied 38 smokers (mean age 25 +/- 6.5 yr), who had 2 fiberoptic bronchoscopic lavages in sequence, the first after 8 h of abstinence from smoking, and the second at varying time intervals after smoking. Twenty-two smokers were tested before, and 10 min to 3 h after, smoking 2 medium-tar filter cigarettes; 16 smokers were were tested before, and 2 min to 60 min after, smoking 4 cigarettes. Eight nonsmoking volunteers had 2 BAL performed in sequence as control subjects. Initial BAL from control subjects and from smokers after 8 h of abstinence had similar alpha-Pl activity (mean 0.495 +/- SD 0.017 micrograms of pancreatic elastase/micrograms alpha-Pl, about 90% of the activity of purified alpha-Pl). After smoking, we did not find significant inactivation of alpha-Pl except in the 6 smokers lavaged 1 h after smoking 2 cigarettes, whose alpha-Pl activity decreased slightly to 90.0 +/- SD 10.6% of their initial activity (p less than 0.05). We also obtained BAL from 7 smokers only after smoking, and did not find inactivation of alpha-Pl. We conclude that in young healthy smokers: (1) alpha-Pl in BAL after 8 h of abstinence from smoking is active similar to nonsmoking control subjects, and (2) after smoking 2 to 4 cigarettes, there is no, or very limited, inactivation of alpha-Pl.