Disproportionality analysis for signal detection of implantable cardioverter-defibrillator-related adverse events in the Food and Drug Administration Medical Device Reporting System.

BACKGROUND: The Food and Drug Administration (FDA) became aware of lead fracture and inappropriate shock events related to Sprint Fidelis leads in January 2007. The manufacturer announced a voluntary market withdrawal in October 2007. AIM: Our aim was to retrospectively evaluate this safety signal using disproportionality analysis to estimate whether disproportionality analysis could have detected this particular safety signal earlier than actually occurred. MATERIALS AND METHODS: The Manufacturer and User Facility Device Experience (MAUDE) database contains reports on device-related adverse events, of which, FDA receives several hundred thousand every year. For each manufacturer, a list of the top lead brand names was ranked by frequency of reports. We used the Multi-item Gamma Poisson Shrinker (MGPS) method for analysis. We isolated 11 top-reported implantable cardioverter defibrillator (ICD) lead brand names. Using MGPS methodology, we calculated the one-sided 95% lower confidence bound EB05 on the empirical Bayes geometric mean of the reporting ratio. RESULTS: We performed individual MGPS analysis for each of the top reported adverse events in 2006 for ICD leads. Fidelis had the highest EB05 scores for lead fractures and inappropriate shock. DISCUSSION: Through disproportionality analysis of the MAUDE database, we were able to identify known safety signals associated with the Medtronic Sprint Fidelis lead. CONCLUSION: If utilized at the time, this disproportionality analysis would have identified signals earlier for lead fractures, oversensing, high impedance, and inappropriate shock.

Outcomes and prognostic factors of systolic as compared with diastolic heart failure in urban America.

We sought to describe a large heart failure (HF) population with respect to systolic and diastolic abnormalities in terms of demographics, echocardiographic parameters, and survival. Using data abstracted from the Resource Utilization Among Congestive Heart Failure (REACH) study, a targeted subpopulation of 3471 patients had electrocardiographic, echocardiographic, and clinical data taken from automated sources during the first year of diagnosis. Among the HF population, 1811 (52.2%) had diastolic HF. Prevalence of diastolic HF trended with age, from 46.4% in those less than 45 years to 58.7% in those 85 years or older (p=0.001 for trend). Patients with diastolic HF had a higher mean ejection fraction (55.7% vs. 28.0%), lower left ventricular end-systolic diameter (3.11 vs. 4.74 cm), and lower left atrium:aortic outlet ratio (1.28 vs. 1.38) (p=0.001 for each comparison). Annualized age, sex, and race-adjusted mortality were 11.2% and 13.0% for those with diastolic and systolic HF, respectively (p=0.001). In a large, racially mixed, urban HF population, those with diastolic HF predominate and enjoy better-adjusted survival than counterparts with systolic HF.

Changes in B-type natriuretic peptide levels in hemodialysis and the effect of depressed left ventricular function.

B-type natriuretic peptide (BNP) is a cardiac neurohormone specifically secreted by the cardiac ventricles in response to volume expansion, pressure overload, and resultant increased wall tension. Previous research has shown elevated BNP levels in patients with volume overload caused by end-stage renal disease (ESRD). This pilot study was designed to describe the relative reduction in BNP that occurs as a result of hemodialysis (HD) in relation to baseline left ventricular function. Hemodialysis patients (n = 34) with ESRD were enrolled in a prospective manner. All patients had blinded serum BNP levels measured at the initiation and termination of HD. Levels of BNP were also measured in the dialysate and any residual urine, if available. In addition, monthly urea reduction ratio (URR) and Kt/V were obtained. The most recent measurement of left ventricular ejection fraction (LVEF) by any method was obtained from chart review. The BNP reduction ratio (BNPRR) was calculated by the following expression: pre-BNP-post-BNP/pre-BNP. The mean age was 50.8 years, 50.0% were male, and 55.9% were African American. A mean of 3239.4 mL of fluid was removed during HD. The mean pre-BNP, post-BNP, and change in BNP were 556.3 +/- 451.5 pg/mL, 538.6 +/- 488.3 pg/mL, and -17.6 +/-147.0 pg/mL. Of the 27 patients who had both pre-BNP and post-BNP values in the measurable range (< 1,300 pg/mL), BNP rose in 9 (33.3%) and fell in 18 (66.7%). The BNPRR had the following correlations: volume removed, r = -0.33, P = .07; Kt/V, r = -0.51, P = .01; URR, r = -0.34, P = .09; and change in body weight, r = -0.33, P = .07. The BNPRR was not correlated with time on dialysis or change in blood pressure. A total of 20 patients had LVEF recorded and post-BNP levels in the measurable range. For this group, the BNPRR values stratified by lowest to highest LVEF group were 4.6%, 19.1%, and 21.8%; P = .95 for trend. The BNP values were elevated in ESRD patients and decreased slightly during HD. This change was more pronounced in patients with normal or mildly impaired LVEF. The BNPRR correlated with the volume removed, change in body weight, and Kt/V. Future research with the BNPRR as a potential marker of the adequacy of volume removal in HD is warranted.

Opportunities for improvement in the diagnosis and treatment of heart failure.

BACKGROUND: Improved treatment of congestive heart failure (CHF) can slow disease progression, promote clinical stability, and prolong survival. HYPOTHESIS: Patterns in diagnostic test utilization and pharmacotherapy among patients with newly diagnosed heart failure may affect outcomes. METHODS: Claims data were analyzed from all diagnostic procedures and prescriptions from 1995 to 1998 in 3,353 patients with heart failure diagnosed within 1 year. Rates of diagnostic testing and categories of drugs prescribed were the main outcome measures. Demographic variables and type of provider were analyzed within a setting whose access to care was controlled. RESULTS: Rates of diagnostic testing with respect to basic, metabolic/endocrine, alternative diagnoses, underlying ischemia, and left ventricular function varied as a function of gender, age, race, and primary versus specialty care provider. Only 4.7% of patients underwent all diagnostics and treatments recommended in current guidelines. However, those patients (27.5%) who underwent an evaluation for ischemic heart disease and were prescribed vasodilators or beta blockers enjoyed the lowest crude mortality. CONCLUSIONS: There are multiple opportunities apparent to improve the initial diagnostic and therapeutic care of patients with heart failure. There appears to be an early survival benefit with respect to use of vasodilators and beta blockers within the first year of treatment.