Likelihood of seizure remission in an adult population with refractory epilepsy.

OBJECTIVE: We aimed to determine the likelihood of remission and its clinical predictors in adult patients meeting a strict definition of refractory epilepsy. We also wanted to investigate the influence of treatment regimen on remission. METHODS: A total of 246 patients with treatment refractory epilepsy (having at least 1 seizure per month and having not responded positively to at least 2 antiepileptic drugs) were identified in 2000 and followed for 3 years. We used Kaplan-Meier methods to estimate the rate of achieving a 6-month terminal seizure remission and Cox regression analysis to evaluate clinical predictors for seizure remission. RESULTS: The estimated 6-month terminal seizure remission rate was 19% (95% confidence interval, 14-26%) for all cases and 14% (95% confidence interval, 10-21%) when limited to those treated only with medication. Negative predictors for remission included a history of status epilepticus, younger age at intractability, number of failed drug therapies, and presence of mental retardation. No specific drug was significantly associated with remission, and frequently, no clear intervention led to terminal remission. INTERPRETATION: Fifteen percent (approximately 5% per year) of a drug refractory epilepsy population obtained a 6-month terminal seizure remission. Our results signify that no matter how many antiepileptic drug therapies have failed, there is always hope of a meaningful seizure remission in this population. Furthermore, we have elucidated four clinical predictors that can aid the epileptologist in prognostication.

Circadian, daily, and seasonal distributions of ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators.

This study investigated the circadian, daily, and seasonal distributions of ventricular arrhythmias in patients with new implantable cardioverter-defibrillator placement at Creighton University Medical Center from January 2000 to December 2004. The incidence and distribution of ventricular tachyarrhythmias as recorded by implantable cardioverter-defibrillators were analyzed with respect to season, month, day of the week, and average daily temperature. Data from 154 consecutive patients (mean age 67 +/- 14 years; 78% men, 71% with ischemic heart disease [IHD], mean left ventricular ejection fraction 34 +/- 15%) were analyzed. During a mean follow-up of 35 +/- 19 months, a total of 1,055 episodes of spontaneously terminated ventricular tachycardia (VT) and 612 episodes of VT or ventricular fibrillation with appropriate device therapy occurred. Distributions in the incidence of VT and VT or ventricular fibrillation receiving appropriate therapy were similar in patients with IHD and non-IHD. Spontaneously terminated VT and appropriately treated VT or ventricular fibrillation episodes occurred with the greatest incidence in the winter months and the lowest incidence in summer, spring, and fall. A linear regression between the number of episodes and the average daily temperature showed a greater likelihood of the 2 events occurring on cooler days, irrespective of the cause of cardiac disease. A weekly distribution was also observed, with the greatest proportion of episodes occurring on Fridays and the lowest on Saturdays and Sundays. A bimodal circadian distribution was present, with the greatest peak occurring from 8 a.m. to 1 p.m. and a smaller peak occurring from 5 p.m. to 10 p.m. In conclusion, the occurrence of ventricular tachyarrhythmias appears to follow circadian, daily, and seasonal distributions that are similar in patients with IHD and non-IHD. The incidence inversely correlates with average daily temperatures.

Meta-analysis: inhibition of renin-angiotensin system prevents new-onset atrial fibrillation.

BACKGROUND: Epidemiologic studies suggest that inhibition of renin-angiotensin system with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may prevent development of atrial fibrillation (AF). OBJECTIVE: The objective of the study was to assess if there is significant indication for using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the prevention of new-onset AF and to identify the target patient population. METHODS: PubMed and Cochrane clinical trials database were searched from 1980 through March 2005 together with the review of citations. Nine randomized controlled human trials reporting the prevention of new-onset AF by inhibition of renin-angiotensin system were identified. Information about study design, follow-up, intervention, population, outcomes, and methodology quality was extracted. RESULTS: The mean follow-up of the studies ranged from 6 months to 6.1 year. The pooled estimate using random effects model was 0.82 (95% CI 0.70-0.97) for prevention of new-onset AF and 0.61 (95% CI 0.46-0.83) for primary prevention of AF. The angiotensin-converting enzyme inhibitors (0.75, 95% CI 0.57-0.99) had greater protective effect than angiotensin receptor blockers (0.81, 95% CI 0.62-1.06). Patients with heart failure benefited the most (0.57, 95% CI 0.37-0.89). The test for heterogeneity between studies was significant. There was no consistent visual or statistical evidence of publication bias. CONCLUSION: The use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers had an overall effect of 18% risk reduction in new-onset AF across the trials and 43% risk reduction in patients with heart failure.

Aldosterone inhibition reduces the risk of sudden cardiac death in patients with heart failure.

Sudden cardiac death (SCD) accounts for over 450,000 deaths annually in the USA. Sudden death is estimated to account for approximately 50% of all deaths from cardiovascular causes. Total cardiac mortality has decreased from 728,115 in 1989 to 719,456 in 1999 but the percentage of deaths that are sudden has actually increased from 38% to 47%. Prevention of SCD in patients with risk factors is a high priority for public health professionals. Aldosterone has been shown to be associated with myocardial inflammation, endothelial dysfunction and fibrosis. There is evidence from clinical trials suggesting the role of aldosterone inhibition in prevention of SCD. We reviewed the potential mechanisms and discuss the clinical implications of Randomised ALdactone Evaluation Study (RALES) and Eplerenone Neurohormonal Efficacy and Survival Study (EPHESUS). The use of aldosterone receptor blockers had an overall effect of 21% risk reduction in SCD. Appropriate monitoring and counselling is essential while using either of the aldosterone inhibitors.

Homocysteine and the risk of ischemic stroke in a triethnic cohort: the NOrthern MAnhattan Study.

BACKGROUND AND PURPOSE: The level of total homocysteine (tHcy) that confers a risk of ischemic stroke is unsettled, and no prospective cohort studies have included sufficient elderly minority subjects. We investigated the association between mild to moderate fasting tHcy level and the incidence of ischemic stroke, myocardial infarction, and vascular death in a multiethnic prospective study. METHODS: A population-based cohort was followed for vascular events (stroke, myocardial infarction, and vascular death). Baseline values of tHcy and methylmalonic acid were measured among 2939 subjects (mean age, 69+/-10; 61% women, 53% Hispanics, 24% blacks, and 20% whites). Cox proportional models were used to calculate hazard ratios (HRs) and 95% CIs in tHcy categories after adjusting for age, race, education, renal insufficiency, B12 deficiency, and other risk factors. RESULTS: The adjusted HR for a tHcy level > or =15 micromol/L compared with <10 micromol/L was greatest for vascular death (HR=6.04; 95% CI, 3.44 to 10.60), followed by combined vascular events (HR=2.27; 95% CI, 1.51 to 3.43), ischemic stroke (HR=2.01; 95% CI, 1.00 to 4.05), and nonvascular death (HR=2.02; 95% CI, 1.31 to 3.14). Mild to moderate elevations of tHcy of 10 to 15 micromol/L were not significantly predictive of ischemic stroke, but increased the risk of vascular death (2.27; 95% CI, 1.44 to 3.60) and combined vascular events (1.42; 95% CI, 1.06 to 1.88). The effect of tHcy was stronger among whites and Hispanics, but not a significant risk factor for blacks. CONCLUSIONS: Total Hcy elevations above 15 micromol/L are an independent risk factor for ischemic stroke, whereas mild elevations of tHcy of 10 to 15 micromol/L are less predictive. The vascular effects of tHcy are greatest among whites and Hispanics, and less among blacks.

Automated vulnerability testing identifies patients with inadequate defibrillation safety margin.

BACKGROUND: Implantable cardioverter-defibrillator system efficacy is tested at implant by induction of ventricular fibrillation (VF). Defibrillation safety margin can be assessed without VF induction using upper limit of vulnerability methods, but these methods have required manual determination of T-wave timing. METHODS AND RESULTS: To test the feasibility of an inductionless system of implant testing, a multicenter prospective study of an automated vulnerability safety margin system was conducted, which measured T-wave timing using an intracardiac electrogram during a ventricular pacing train. The system delivered up to 4 T-wave shocks of 18 J. Lack of VF induction by all 4 shocks was considered evidence of defibrillation adequacy. Patients subsequently underwent conventional defibrillation testing to meet a standard implant criterion. The 95% lower CI for defibrillation success at 25 J for noninduced patients was found using Bayesian statistics. Sixty patients were enrolled at 6 centers. Vulnerability testing and defibrillation success results were obtained from 54 patients. Vulnerability testing induced VF in 10 (19%) patients, of whom 2 required system revision. All patients not induced by vulnerability testing were successfully defibrillated twice at ≤25 J. The Bayesian credible interval was 97% to 100% for the population success rate of defibrillation at 25 J for automated vulnerability safety margin noninduced patients. CONCLUSIONS: An automated system identified all patients who failed conventional safety margin testing, while inducing only 19% of patients. Although limited by sample size, this study suggests the feasibility of automated implant testing that substantially reduces the need for VF induction in patients receiving implantable cardioverter-defibrillators.

Evaluation of left ventricular dyssynchrony using combined pulsed wave and tissue Doppler imaging.

INTRODUCTION: The combination of pulsed wave (PW) and tissue Doppler imaging (TDI) has been proposed as a new method to assess left ventricular (LV) mechanical dyssynchrony (LVMD), but results have not been validated. We investigated the correlation of a combination of PW and TDI with a positive response to cardiac resynchronization therapy (CRT). MATERIAL AND METHODS: We studied 108 consecutive patients who received CRT. Patients with atrial fibrillation were excluded. The time difference (T(PW-TDI)) between onset of QRS to the end of LV ejection by PW (T(PW)) and onset of QRS to the end of the systolic wave in LV basal segments with greatest delay by TDI (T(TDI)) was measured before CRT and during short-term and long-term follow-up. RESULTS: The T(PW-TDI) interval before CRT was 74 ±48 ms. Intra-observer variabilities for T(PW) and T(TDI) were 1.5 ±0.24% and 1 ±0.17%. Inter-observer variabilities for T(PW) and T(TDI) were 1 ±0.36% and 1 ±0.64%, respectively. T(PW-TDI) > 50 ms was defined as the cutoff value for diagnosis of LVMD by receiver operating curve (ROC) analysis. During follow-up of 15 ±11 months, the sensitivity and specificity of TP(PW-TDI) to predict a positive response to CRT were 98% and 82%, respectively. The area under the ROC curve was 0.92. There was a significant agreement between LVMD determined by T(PW-TDI) and the positive response to CRT (κ=0.80). CONCLUSIONS: Left vertricular dyssynchrony detected by the method combining PW and TDI demonstrated a high reproducibility, sensitivity, specificity and agreement with a positive response to CRT.

C-Reactive Protein and The Risk of Atrial Fibrillation: A Systematic Review and Meta-Analysis.

There is increasing evidence linking C-reactive protein (CRP) and atrial fibrillation (AF). Despite the abundance of literature, confusion exists regarding this association because of inconsistent results. MEDLINE and Cochrane Controlled Trials Register databases were carefully searched through July, 2009 combining the following terms "C-reactive protein" and "atrial fibrillation". Reference lists of selected articles and reviews were also screened to identify additional relevant studies. Of the 129 studies initially identified, 8 studies with 7507 subjects (719 with AF) were included in the meta-analysis. Analysis yielded a relative risk of 1.63 (1.43, 1.86) for occurrence of AF when CRP level was above a cut off of 3-3.5 mg/l. When 3 studies with data on a higher cut off of 4.5-5.0 mg/l were analyzed separately, the relative risk was 4.03 (3.1, 5.25). Our study suggests that elevated CRP is associated with increased risk for AF. The risk appears incremental with higher CRP levels conferring proportionately increased risk. There is an urgent need for further large scale, well designed prospective studies to assess the relationship between CRP and AF.

Impact of moderate to severe renal impairment on mortality and appropriate shocks in patients with implantable cardioverter defibrillators.

Background. Due to underrepresentation of patients with chronic kidney disease (CKD) in large Implantable-Cardioverter Defibrillator (ICD) clinical trials, the impact of ICD remains uncertain in this population. Methods. Consecutive patients who received ICD at Creighton university medical center between years 2000-2004 were included in a retrospective cohort after excluding those on maintenance dialysis. Based on baseline Glomerular filtration rate (GFR), patients were classified as severe CKD: GFR < 30 mL/min; moderate CKD: GFR: 30-59 mL/min; and mild or no CKD: GFR ≥ 60 mL/min. The impact of GFR on appropriate shocks and survival was assessed using Kaplan-Meier method and Generalized Linear Models (GLM) with log-link function. Results. There were 509 patients with a mean follow-up of 3.0 + 1.3 years. Mortality risk was inversely proportional to the estimated GFR: 2 fold higher risk with GFR between 30-59 mL/min and 5 fold higher risk with GFR < 30 mL/min. One hundred and seventy-seven patients received appropriate shock(s); appropriate shock-free survival was lower in patients with severe CKD (GFR < 30) compared to mild or no CKD group (2.8 versus 4.2 yrs). Conclusion. Even moderate renal dysfunction increases all cause mortality in CKD patients with ICD. Severe but not moderate CKD is an independent predictor for time to first appropriate shock.

Effect of mitral regurgitation on cerebrovascular accidents in patients with atrial fibrillation and left atrial thrombus.

BACKGROUND: The effect of mitral regurgitation (MR) on the incidence of new cerebrovascular accidents (CVA) and mortality in patients with atrial fibrillation (AF) and left atrial thrombus (LAT) is unknown. OBJECTIVE: To investigate the effect of MR in patients with AF and LAT on new CVA and mortality. METHODS: Eighty nine consecutive patients, mean age 71 years, with AF and LAT documented by transesophageal echocardiography were investigated to determine the prevalence and severity of MR and the association of the severity of MR with new cerebrovascular accidents (CVA) and mortality at 34-mo follow-up. RESULTS: Of 89 patients, 1 + MR was present in 23 patients (26%), 2 + MR in 44 patients (50%), 3 + MR in 17 patients (19%), and 4 + MR in 3 patients (4%). Mean follow-up was 34 +/- 28 mo. The Cox proportional hazards model showed that the severity of increased MR did not significantly increase new CVA or mortality at 34-mo follow-up. The only variable predictive of mortality was left ventricular ejection fraction (LVEF), and with every unit increase in LVEF, the risk decreased by 3%. CONCLUSION: MR occurred in 87 of 89 patients (98%) with AF and LAT. There was no association between the severity of MR and the incidence of CVA or mortality.

Socioeconomic status is a risk factor for epilepsy in Icelandic adults but not in children.

PURPOSE: Two earlier population-based studies provide conflicting information on the association between low socioeconomic status (SES) and risk for epilepsy. Seizure etiologies (e.g., head injury, stroke) associated with low SES were not addressed in prior analyses. We assess the relation between SES indices and incident epilepsy separately for children and adults and in subgroups defined by seizure etiology. METHODS: In this population-based case-control study, a surveillance system identified incident unprovoked seizure or first diagnosis of epilepsy throughout Iceland (n = 418). Controls were selected from the population registry as the next two same-sex births alive, residing in Iceland at the time of the index seizure, and without a history of unprovoked seizure on the date of the case's incident seizure (n = 835). The odds ratio measured the association between SES and epilepsy. RESULTS: An association was found between epilepsy and SES among adults, but not among children. Among adults, low education was associated with an increased risk for epilepsy [odds ratio (OR), 2.29; 95% confidence interval (CI), 1.21-4.34), and home ownership was protective (OR, 0.63; 95% CI, 0.43-0.92). When analyses were repeated by seizure etiology, this association remained only in the group with epilepsy of unknown cause, even after adjusting for alcohol consumption. CONCLUSIONS: Low SES, indexed by low education or lack of home ownership, is a risk factor for epilepsy in adults, but not in children, suggesting a cumulative effect of SES on risk for epilepsy. This association is not explained by established risk factors for epilepsy (e.g., head injury, stroke). We find no evidence of a downward social drift among cases whose parents had epilepsy.