No abstract

In patients receiving an ICD for primary prevention of sudden death, CKD significantly reduced long-term survival. This poor prognosis may limit the impact of primary prevention ICD therapy in this patient population.

Objective: To examine the possibility that lower serum bioavailable testosterone concentrations, without increased LH release, in healthy older men, reflects hypothalamic GnRH deficiency. Design: We used a randomized, double-blind, placebo-controlled design. Methods: We treated each of five young (ages 20-34 years) and five older (ages 60-78 years) men with 2 weeks of randomized infusions of saline or pulsatile GnRH (100 ng/kg i.v. every 90 min). Results: At baseline (saline infusion), older men had more LH pulses (young compared with old, 10 Ϯ 0.6 compared with 15 Ϯ 1, P = 0.0026) per 24 h, reduced fractional LH pulse amplitude (219 Ϯ 17% compared with 167 Ϯ 40%, P = 0.0376), and more disorderly hormone release as judged by approximate entropy (ApEn) (LH, P Յ 0.0001; testosterone, P Յ 0.0047). In response to pulsatile i.v. GnRH infusions, serum 24-h LH concentrations (measured by immunoradiometric assay (IRMA)), increased equivalently in young and older men (to 7.3 Ϯ 1.2 and 7.2 Ϯ 1.8 IU/l respectively). GnRH treatment also normalized LH pulse frequency and amplitude, ApEn, and plasma biologically active LH (pooled) concentrations. In contrast, 24-h testosterone concentrations failed to increase equivalently in older men (young compared with old, 869 Ϯ 88 compared with 517 Ϯ 38 ng/dl, P = 0.0061), reflecting lower testosterone peak maxima (995 Ϯ 108 compared with 583 Ϯ 48 ng/dl, P = 0.0083) and interpeak nadirs (750 Ϯ 87 compared with 427 Ϯ 26 ng/dl, P = 0.0073). Conclusions:We have demonstrated that, in older men, successful reconstitution of 24-h pituitary (bioactive) LH output and pulsatile (IRMA) LH release patterns could be achieved by a fixed exogenous GnRH pulse signal, thereby implicating altered endogenous hypothalamic GnRH release in the relative hypogonadotropism of aging. The failure of testosterone concentrations to increase concomitantly points to a simultaneous Leydig cell defect. We conclude that aging in men is marked by a dual defect in the central nervous system-pituitary-Leydig cell axis.

No abstract

Objective: To use novel statistical methods for analyzing the effect of lesion set on (long-standing) persistent atrial fibrillation (AF) in the Cardiothoracic Surgical Trials Network trial of surgical ablation during mitral valve surgery (MVS). Methods: Two hundred sixty such patients were randomized to MVS + surgical ablation or MVS alone. Ablation was randomized between pulmonary vein isolation and biatrial maze. During 12 months postsurgery, 228 patients (88%) submitted 7949 transtelephonic monitoring (TTM) recordings, analyzed for AF, atrial flutter (AFL), or atrial tachycardia (AT). As previously reported, more ablation than MVS-alone patients were free of AF or AF/AFL at 6 and 12 months (63% vs 29%; P < .001) by 72-hour Holter monitoring, without evident difference between lesion sets (for which the trial was underpowered). Results: Estimated freedom from AF/AFL/ATon any transmission trended higher after biatrial maze than pulmonary vein isolation (odds ratio, 2.31; 95% confidence interval, 0.95–5.65; P = .07) 3 to 12 months postsurgery; estimated AF/AFL/AT load (ie, proportion of TTM strips recording AF/AFL/AT) was similar (odds ratio, 0.90; 95% confidence interval, 0.57–1.43; P .6). Within 12 months, estimated prevalence of AF/AFL/AT by TTM was 58% after MVS alone, and 36% versus 23% after pulmonary vein isolation versus biatrial maze (P<.02). Conclusions: Statistical modeling using TTM recordings after MVS in patients with (long-standing) persistent AF suggests that a biatrial maze is associated with lower AF/AFL/AT prevalence, but not a lower load, compared with pulmonary vein isolation. The discrepancy between AF/AFL/AT prevalence assessed at 2 time points by Holter monitoring versus weekly TTM suggests the need for a confirmatory trial, reassessment of definitions for failure after ablation, and validation of statistical methods for assessing atrial rhythms longitudinally.