Optimal Timing of Implantable Cardioverter‐Defibrillator Implantation After Myocardial Infarction: A Decision Analysis

ICD Implant Timing . Background: The optimal timing of implantable cardioverter defibrillator (ICD) placement for the primary prevention of sudden cardiac death after myocardial infarction (MI) remains unknown. Methods and Results: We developed a Markov model to investigate the optimal timing of ICD implantation after MI (no ICD, ICD at 60 days, 6 months, and 1 year) in patients who meet current guidelines. Estimates of arrhythmic death (baseline risk 6%, range 1–20% per year), nonarrhythmic death, and ICD efficacy were based upon MADIT‐II and other contemporary post‐MI clinical trials. We used both deterministic and stochastic modeling processes in our analysis. After 10 years follow‐up, the baseline probability of survival was higher in those treated with ICD implantation versus not (42% vs 30%, P < 0.001). Survival was highest with ICD implantation at 60 days versus 6 months versus 1 year: 42.4%, 42.3%, and 42.0% (P = 0.0028). ICD implantation at 60 days provided a mean incremental survival of 0.28 months and 0.84 months per patient (compared with implantation at 6 months and 1 year). In sensitivity analyses, patients’ competing risk for nonarrhythmic death was the primary determinant of benefit from ICD implantation. Overall, ICD implantation at 60 days resulted in the greatest life expectancy over a wide range of plausible nonarrhythmic and arrhythmic death rates. Conclusions: The benefits of early ICD implantation are modest when compared with delayed implantation at 6 months/1 year. Our results suggest that making sure a patient receives an ICD, when appropriate, may be more important than the timing of the implantation procedure. (J Cardiovasc Electrophysiol, Vol. pp. 791‐798, July 2010)     

Immunogenicity, Antigenicity, and Endothelial Viability of Aortic Valves Preserved at 4°C in a Nutrient Medium

In patients undergoing aortic valve replacement, allograft valves stored at 4 degrees C in a nutrient medium have been associated with excellent immediate and long-term results. The effects of this method of prolonged storage on the antigenic, immunological and cellular characteristics of these grafts are incompletely understood. This study was designed to study these phenomena in rat aortic valves subjected to antibiotic sterilization and stored for up to 3 weeks in RPMI containing 10% fetal calf serum. Selected valves from Brown Norway rats were implanted heterotopically into the abdominal aorta of Lewis rats. Other valves were studied prior to transplantation. Antigenicity was determined by immunocytochemical staining using monoclonal mouse antibodies directed at Class I and Class II rat antigens. Immunogenicity was determined by duration of second-set skin graft survival following heterotopic aortic valve implant. Endothelial cell viability was determined by flow cytometric analysis of endothelial cells harvested from aortic valve allografts by collagenase digestion. Only fresh valves and valves stored for 1 day were positive for Class I antigens; no valves were positive for Class II antigens. Duration of skin graft survival was prolonged with greater duration of storage, but grafts remained immunogenic after 21 days of storage. Endothelial cell viability declined from 95% in the fresh valves to 64% after 21 days of storage. With prolonged duration of allograft valve storage at 4 degrees C, there is an attenuation of antigenicity, immunogenicity, and endothelial cell viability. Loss of endothelial cells may contribute to the changes in immunological responses to the valve allografts. The expression of antigens on the endothelial surface is not a reliable predictor of immunological response.     

Distinguishing acyclovir neurotoxicity from encephalomyelitis

Abstract. Objectives. To define the clinical characteristics of acyclovir neurotoxicity and to outline how to distinguish it from viral encephalitis. Design. Case series of acyclovir neurotoxicity. Setting. All cases reported in Index Medicus or in bibliographic reviews of acyclovir neurotoxicity plus two representative studies of Varicella zoster and Herpes simplex virus encephalitis. Subjects. Thirty-five patients who developed neuropsychiatry symptoms during acyclovir therapy. Interventions. Analysis of the patients' demographics, risk factors, acyclovir dosages and duration, clinical and laboratory findings and outcome. Main outcome measures. All clinical and laboratory findings that were statistically significantly different from viral encephalitis. Results. The median age was 53.3 years. The most common predisposing factors were the use of other potentially neurotoxic medications (17 cases) and acute or chronic renal failure (15 cases). Acyclovir levels were frequently found above the therapeutic range. The characteristic manifestations were confusion (15 cases), hallucination or delirium (9 cases), agitation (8 cases) and lethargy (10 cases). Few patients had associated tremors (11 cases). Fever, headache, seizures and focal neurologic findings were distinctly rare. Cerebrospinal fluid and computed tomography were normal except in patients with other central nervous system disorders. Symptoms appeared within 2 days of therapy in the majority and resolved completely within several days of discontinuing acyclovir. Conclusions. Acyclovir neurotoxicity is a self-limiting, dose-dependent phenomenon which is more common in the elderly, in patients with renal failure or in association with other neurotoxic medications. It is distinguished from viral encephalitis by its sudden onset, absence of fever or headache, lack of focal neurologic findings and normal cerebrospinal fluid.     

Remote Monitoring of Implantable Cardioverter Defibrillators versus Quarterly Device Interrogations in Clinic: Results from a Randomized Pilot Clinical Trial

ICD: Remote Monitoring Versus Clinic Interrogations . Introduction: Remote monitoring is increasingly becoming the new standard of care for implantable cardioverter defibrillator (ICD) follow‐up. We sought to determine whether remote monitoring of ICDs improves patient outcomes compared with quarterly device interrogations in clinic. Methods and Results: In this single‐center pilot clinical trial, adult patients with an ICD were randomly assigned to remote monitoring versus quarterly device interrogations in clinic. The primary endpoint was a composite of cardiovascular hospitalization, emergency room visit for a cardiac cause, and unscheduled visit to the electrophysiology clinic for a device‐related issue at 1 year. We also examined health‐related quality of life, costs, and patient satisfaction with their ICD care. Of 151 patients enrolled in this trial, 76 were randomized to remote monitoring and 75 to quarterly device interrogations in clinic. There was no significant difference in the primary endpoint (32% in the remote monitoring arm vs 34% in the control arm; P = 0.8), mortality, or cost between the 2 arms. Quality of life and patient satisfaction were significantly better in the control arm than in the remote monitoring arm at 6 months (83 [25th, 75th percentiles 70, 90] vs 75 [50, 85]; P = 0.002 and 88 [75, 100] vs 75 [75, 88]; P = 0.03, respectively), but not at 12 months. Conclusion: We showed no significant reduction in cardiac‐related resource utilization with remote monitoring of ICDs. However, given the small number of patients in our study, the real clinical and health economics impact of remote monitoring needs to be verified by a large, multicenter, randomized clinical trial. (J Cardiovasc Electrophysiol, Vol. 21, pp. 545‐550, May 2010)     

The effect of subsequent myocardial damage on the expression of coxsackievirus B4 myocarditis and the development of ventricular aneurysms

Coxsackievirus B (CB) 4 causes transmural myocarditis in sucklingmice with ensuing development of focal ventricular thinningor aneurysms. We studied whether subsequent infection with anothercardiotropic virus influences the expression of CB4 disease. CB4 infection was established in 2-day-old CD1 mice by intraperitoneal(IP) inoculation. Three weeks later, surviving animals wererandomized to receive CB3 or saline IP. They were then killedover a 45-day period. CB4 neutralizing antibody (NA) titreswere comparable in both groups (31 ± 23 vs 37 ±19). CB3 NA were detected in CB3 infected animals only (72 ±86 versus 0). The incidence of myocarditis was comparable (67.4%vs 55.2%). The indices of histopathological changes (assessedaccording to a semiquantitative grading scale from 0-4) weregreater among CB3 recipients on day 9 post CB3 challenge (1.38 ± 0. 43 vs 046 ± 0. 4, P<0001) and to alesser extent, on day 13 (056 ± 0. 56 vs 019 ±0. 38, P>0. 1). On days 30, and 45, these indices becamesimilar in both groups. Focal thinning was noted on day 45 in6111 animals with CB4 infection alone and in 0111 mice withsubsequent CB3 infection (P = 0.006). These findings show that CB3 myocarditis can be expressed inmice with prior CB4 disease, that sequential infections do notlead to cumulative cardiac injury, and that subsequent CB3 infectionsuppresses the formation of CB4 induced ventricular aneurysms.     

STRAIN RELATEDNESS IN PERSISTENT AND RECURRENT CANDIDURIA

Purpose

We assessed the value of determining strain relatedness in differentiating persistent from recurrent candiduria.

Materials and Methods

Prospective monitoring of patients with candiduria (10⁴ or greater colony forming units per ml.) during a 5-month period. All patients with persistent or recurrent infection after documented clearance were selected. Pair isolates were typed using restriction endonuclease analysis of genomic deoxyribonucleic acid with SfiI. Isolates were considered related if all deoxyribonucleic acid bands matched.

Results

We encountered 22 and 5 patients with persistent and recurrent infection, respectively. The isolates were recovered 1 to 140 days apart (21.56 +/− 28.97). Most patients were women (85.2%) with a mean age of 66.41 +/− 18.11 years. Risk factors included antibiotics (100%), indwelling catheter (88.9%) and diabetes mellitus (40.7%). Of 15 individuals who received antifungal therapy candiduria persisted in 10 and resolved but recurred within 4 to 26 days (13.00 +/− 9.08) after treatment in 5. Candida albicans accounted for 34 of 58 isolates (58.6%), and it was mixed with other species in 4 cultures. Paired strains were genetically identical in 26 of 27 patients. Strain persistence was documented in 21 of 22 cases with persistent infection and in all 5 patients with recurrent disease.

Conclusions

These findings show that strain persistence is exceedingly frequent in candiduria. These results imply that determining strain relatedness of Candida urinary isolates may not be reliable in differentiating persistent from recurrent infection.