Single-chamber ICD, single-zone therapy in primary and secondary prevention patients: the simpler the better?

BACKGROUND: It is now well established that implantable cardioverter defibrillator (ICD) implantation reduces mortality in patients at increased risk of sudden cardiac death. However, the best programming parameters remain controversial. Our traditional policy has followed a simple approach in the vast majority of patients. In accordance with ICD programming in the major randomized clinical trials, we programmed a single high-rate, shock-only therapy zone. We aimed to demonstrate in this observational study that simple programming is not associated with higher shock rates or mortality when compared to other published studies. METHODS: Consecutive patients who underwent single-chamber ICD implantation with single-zone, high-rate programming at our institution between 1993 and 2008 were retrospectively studied. Data were collected prospectively in a database regarding details of ICD implantation, demographic data, and indication. RESULTS: Three hundred thirty-two patients were included in our study, 31 % primary prevention and 68 % secondary prevention. Mean ejection fraction (EF) is 33.7 ± 15.3. Over a mean follow-up period of 62.5 ± 38.1 months, 135 patients experienced ICD shock (annualized event rate 7.7 %); 89 patients (26.8 %) appropriate shock in VT-ventricular fibrillation (VF), 68 patients (20.5 %) inappropriate shocks, and 22 patients (6.6 %) both. Twenty-nine patients (8.7 %) were reprogrammed to additional VT-ATP zones. Twenty-two (6.6 %) patients underwent heart transplantation. Sixty-two patients (18.6 %) died during follow-up, 43.6 % out of them due to cardiac cause, mainly progressive heart failure. CONCLUSION: Our results show that simpler settings with single-zone, high-rate programming is associated with ICD shock rates and long-term mortality that does not appear to be worse when compared with contemporary studies which include multizone ICD programming with antitachycardia pacing activated.

GHRH proliferative action on somatotrophs is cell-type specific and dependent on Pit-1/GHF-1 expression.

To investigate the mechanisms by which the hypothalamic peptide GHRH influences cell division, we analyzed its effects on the proliferation of two different cell lines: CHO-4, an ovary-derived cell line, and GH3, a pituitary-derived cell line. We found that GHRH induces the proliferation of pituitary-derived cells but inhibits the proliferation of ovary-derived cells. We further characterized this dual effect of GHRH to find that the cytoplasmic signals induced by this hormone are similar in both cell lines. Moreover, in CHO-4 cells GHRH stimulates two well-known positive cell cycle regulators, c-myc and cyclin D1, but is unable to induce the degradation of the negative cell cycle regulator p27(Kip1). Significantly, when the Pit-1/GHF-1 gene is exogenously expressed in CHO-4 cells, the negative effect of GHRH on the proliferation of these cells is attenuated. Furthermore, when the levels of Pit-1 are downregulated by siRNA in GH3-GHRHR cells, the positive effects of GHRH on the proliferation of these cells are diminished. These findings add to our understanding of the molecules involved in the regulation of cell proliferation by GHRH, as we demonstrate for the first time that Pit-1 is not only required to drive the expression of the GHRH receptor, as previously described, but is also needed for the downstream effects that occur after its activation to modulate cell proliferation. These data suggest that the regulation of cell proliferation in response to a specific growth factor depends in certain cell populations on the presence of a tissue-specific transcription factor.