Screening for Fabry Disease in patients with unexplained left ventricular hypertrophy.

Fabry Disease (FD) is a systemic disorder that can result in cardiovascular, renal, and neurovascular disease leading to reduced life expectancy. FD should be considered in the differential of all patients with unexplained left ventricular hypertrophy (LVH). We therefore performed a prospective screening study in Edmonton and Hong Kong using Dried Blood Spot (DBS) testing on patients with undiagnosed LVH. Participants found to have unexplained LVH on echocardiography were invited to participate and subsequently subjected to DBS testing. DBS testing was used to measure α-galactosidase (α-GAL) enzyme activity and for mutation analysis of the α-galactosidase (GLA) gene, both of which are required to make a diagnosis of FD. DBS testing was performed as a screening tool on patients (n = 266) in Edmonton and Hong Kong, allowing for detection of five patients with FD (2% prevalence of FD) and one patient with hydroxychloroquine-induced phenocopy. Left ventricular mass index (LVMI) by GLA genotype showed a higher LVMI in patients with IVS4 + 919G > A mutations compared to those without the mutation. Two patients were initiated on ERT and hydroxychloroquine was discontinued in the patient with a phenocopy of FD. Overall, we detected FD in 2% of our screening cohort using DBS testing as an effective and easy to administer screening tool in patients with unexplained LVH. Utilizing DBS testing to screen for FD in patients with otherwise undiagnosed LVH is clinically important due to the availability of effective therapies and the value of cascade screening in extended families.

Practice patterns and clinical outcomes among non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients presenting to primary and tertiary hospitals: insights from the EARLY glycoprotein IIb/IIIa inhibition in NSTE-ACS (EARLY-ACS) trial.

OBJECTIVES: We evaluated patients at tertiary [both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) capable] and primary hospitals in the EARLY-ACS trial. BACKGROUND: Early invasive management is recommended for high-risk non-ST-segment elevation acute coronary syndromes. METHODS: We evaluated outcomes in 9,204 patients presenting to: tertiary sites, primary sites with transfer to tertiary sites ("transferred") and those who remained at primary sites ("non-transfer"). RESULTS: There were 348 tertiary (n = 7,455 patients) and 89 primary hospitals [n = 1,749 patients (729 transferred; 1,020 non-transfer)]. Significant delays occurred in time from symptom onset to angiography (49 hr), PCI (53h), and CABG (178 hr) for transferred patients (P < 0.001). Non-transfer patients had less 30-day death/myocardial infarction [9.4% vs. 11.7% (tertiary); adjusted odds ratio (OR): 0.78 (0.62-0.97), P = 0.026]; transferred (14.0%) and tertiary patients were similar [adjusted OR: 1.23 (0.98-1.53), P = 0.074]. Non-transfer patients had lower 1-year mortality [4.3% vs. 6.3% (tertiary); adjusted hazard ratio (HR): 0.64 (0.47-0.87), P = 0.005]: there was no difference between transferred and tertiary patients [5.2% vs. 6.3%; adjusted HR: 0.80 (0.58-1.12), P = 0.202]. Despite similar rates of catheterization, GUSTO severe/moderate bleeding within 120 hr was less in non-transfer [3.1% vs. 6.7% (tertiary); adjusted OR: 0.47 (0.32-0.68), P < 0.001], whereas transferred (6.1%) and tertiary patients were similar [adjusted OR: 0.94 (0.68-1.30), P = 0.693]. There was no difference in non-CABG bleeding. CONCLUSIONS: Timely angiography and revascularization were often not achieved in transferred patients. Non-transferred patients presenting to primary sites had the lowest event rates and the best long-term survival.

A 19-year study on pacemaker-related infections: a claim for using postoperative antibiotics.

BACKGROUND: Although the incidence of pacemaker-related infection (PMINF) is low, it necessitates removal of the pacing system. There is currently no consensus on antibiotics during implantation. METHODS: A prospective database on patients undergoing pacemaker surgery from 1991 to 2009 was reviewed to determine factors associated with PMINF. Specifically, three eras of antibiotic use were compared to elucidate the effect of antibiotics on PMINF: no antibiotics, perioperative antibiotics, and peri- plus postoperative antibiotics. RESULTS: There were 3,253 procedures with PMINF identified in 46 (1.4%) patients. Over 19 years, PMINF incidence fell from 3.6% (no antibiotics) to 2.9% (perioperative antibiotics), to 0.4% (peri- plus postoperative antibiotics). On univariate analysis, the following were associated with PMINF: nonuse of postoperative antibiotics (3.0% vs 0.4%, P < 0.001), year of implant (P < 0.001), repeat procedures (2.3% vs 1%, P = 0.006), nonuse of perioperative antibiotics (3.6% vs 1.3%, P = 0.027). With postoperative antibiotics, rates were significantly reduced in new implants (1/1,289 = 0.1% vs 22/967 = 2.3%, P < 0.001) and repeat procedures (7/692 = 1.0% vs 16/305 = 5.2%, P < 0.001). On multivariate analysis, the following were significant (standardized coefficients denote relative importance): postoperative antibiotics (0.776), repeat procedures (0.508), year of implant (0.142), perioperative antibiotics (0.088). CONCLUSIONS: The PMINF rate is reduced significantly by perioperative antibiotics with a further significant reduction with postoperative antibiotics. However, the reduction in PMINF rate could be a result of changes in practice in the different time eras. This study suggests consideration of perioperative followed by postoperative antibiotics to minimize pacemaker infections.

Pacemaker longevity: are we getting what we are promised?

BACKGROUND: Although pacemaker manufacturers provide projections on longevity, these projections cannot be relied upon due to the assumptions of output parameters being far in excess of those programmed in clinical practice. OBJECTIVE: The purpose of this review was to compare the actual longevity to the calculated longevity of pacemakers based on battery cell characteristics taking into account individual programmed parameters, mode, degree of usage, and percent pacing. This was also compared to the manufacturers' own projected longevities. METHODS: Patients who had a pacemaker replaced between 1998 and 2003 were included (n = 124). Cell characteristics were obtained from manufacturers and programmed parameters were obtained at each visit. Stepwise calculations were done for each visit to find current drain during each interval, and then were used in a weighted average to find the total average lifetime current drain. This was subsequently used to find a calculated longevity for each pacemaker to be compared to the actual longevity observed. RESULTS: The pacemakers lasted 491+/-92 days (mean+/-SEM) less than calculated. There was also a difference between dual- and single-chamber devices (though not statistically significant). Moreover, it was found that there were significant differences between manufacturers. CONCLUSIONS: There appears to be a significant discrepancy between calculated and actual longevities, confirming that battery depletion occurs earlier than expected. This suggests that current drain expended for ancillary functions may be considerable. Another factor may be pre-implantation drain. Vigilance with programming of outputs, modes, sensors, heart rates, and ancillary functions could potentially extend longevity and postpone/obviate the need for costly repeat surgery with its attended risk of complications. Furthermore, the differences between manufacturers seem to parallel the clinical impressions.