ABSTRACT
BACKGROUND: In 2007, Medtronic Sprint Fidelis defibrillator leads were taken off the market due to a high rate of lead failure. Current data do not allow for risk stratification of patients with regard to lead failure. AIMS: We sought to determine predictors of Sprint Fidelis lead failure. METHODS: Between 2004 and 2007, 269 Sprint Fidelis leads were implanted in 258 patients in our centre. Variables associated with lead failure were assessed by the Kaplan-Meier method and a Cox survival model. RESULTS: During a median follow-up of 2.80 years (maximum 5.32), we observed 33 (12.3%) Sprint Fidelis lead failures (5-year survival, 65.6% ± 7.5%). In univariate analysis, age was the only predictor of lead failure (hazard ratio [HR] for 1-year increase 0.97; 95% confidence interval [CI] 0.95-0.99; p=0.009). Patients aged<62.5 years (median) had a significantly increased risk of lead failure compared with patients aged>62.5 years (HR 2.80; CI 1.30-6.02; p=0.009). Survival without Sprint Fidelis lead failure was 55.6% ± 10.4%) in patients aged<62.5 years (24/134 leads) vs 78.6% ± 8.8% in patients aged>62.5 years (9/135 leads). The annual incidence of lead failure in patients aged<62.5 years was 11.6% ± 4.9% during the fourth year after implantation and 22.9% ± 13.2% during the fifth year. CONCLUSION: Overall, we found a higher rate of Sprint Fidelis lead dysfunction than previously described. Lead failure was much more frequent in younger patients. Our results emphasize the need for close follow-up of younger patients with Sprint Fidelis leads and suggest that, in these patients, the implantation of a new implantable cardioverter defibrillator lead at the time of generator replacement might be reasonable.
Subject(s)
Aging , Defibrillators, Implantable/statistics & numerical data , Equipment Failure/statistics & numerical data , Age Distribution , Aged , Algorithms , Analysis of Variance , Arrhythmias, Cardiac/therapy , Confidence Intervals , Female , Follow-Up Studies , France , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Risk FactorsABSTRACT
BACKGROUND: CXCL12, a constitutive chemokine (ligand of CXCR4 and CXCR7), is expressed in the skin and airway epithelium and plays a significant role in allergic airway diseases. The pleiotropic effects of CXCL12 are enhanced by cofactors specific to the target cell. OBJECTIVE: We hypothesized that histamine, a major mediator of allergic reactions, could interact with CXCL12 to promote human mast cell (MC) migration. METHODS: The chemotactic effects of CXCL12 alone or in combination with histamine were evaluated on human precursor and mature MCs by using in vitro migration assays. RESULTS: CXCL12 exerts a chemotactic activity on both precursor and fully mature MCs. Histamine and supernatants from IgE-activated MCs enhanced CXCL12 chemotactic activity on the precursor MC population. The synergy between histamine and CXCL12 was not observed with mature MCs, CD4(+) T cells, and monocytes. Inhibition of histamine receptors pharmacologically or with specific small interfering RNA (siRNA) indicated that synergy between histamine and CXCL12 required the H(4) receptor. CONCLUSION: Histamine released by allergen-activated mature MCs might promote MC-rich allergic inflammation by enhancing recruitment of their precursors in tissues constitutively expressing CXCL12, including skin and airways. CLINICAL IMPLICATIONS: This work highlights a novel role of the H(4) receptor in the perpetuation of allergic responses and provides evidence for the utility of H(4) receptor antagonists in the treatment of allergic diseases.
