Comparison of management patterns and clinical outcomes in patients with atrial fibrillation in Canada and the United States (from the analysis of the Atrial Fibrillation Follow-up Investigation of Rhythm Management [AFFIRM] database)

Little is known about differences in practice patterns or outcomes in the management of patients who have atrial fibrillation in Canada compared with those in the United States (US). We evaluated the effect that the country of enrollment may have on the management patterns and clinical outcomes in patients who participated in the AFFIRM study. Three thousand four hundred patients came from the US and 660 from Canada. In the US, patients were more likely to have a history of coronary artery disease (39% vs 35%, p = 0.03), hypertension (72% vs 67%, p = 0.01), or congestive heart failure (24% vs 18%, p = 0.0002). More US participants were <65 years of age (25% vs 19%, p = 0.003). Although at randomization the use of warfarin was comparable, during follow-up Canadians were more likely to be treated with warfarin and to be therapeutically anticoagulated. Mortality rate at 5 years was higher in US patients (24% vs 16%, p = 0.001), and the composite end point (death, disabling stroke, major bleeding, cardiac arrest, or anoxic encephalopathy) was also higher in US patients (30% vs 22%, p = 0.0005). Even after adjusting for known differences in baseline characteristics, the risk of death was lower in Canada (hazard ratio 0.70, p = 0.02). In conclusion, in the AFFIRM study, US subjects were more likely to have preexisting cardiovascular diseases despite being younger (<65 years old) than those in Canada. Effective warfarin therapy was more commonly employed in Canada. After correcting for the known differences in baseline characteristics, Canadian patients who had atrial fibrillation had a lower mortality risk.     

sICAM-1 correlates with myocardial ICAM-1 expression in dilated cardiomyopathy

BACKGROUND: Dilated cardiomyopathy (DCM) is etiopathogenically linked to intramyocardial inflammation, which is reflected by ICAM-1 abundance. We investigated whether soluble ICAM-1 (sICAM-1) levels in the sera of DCM patients are associated with intramyocardial ICAM-1 expression. METHODS: Immunohistochemically detected ICAM-1 expression was quantified semiquantitatively in endomyocardial biopsies from DCM patients (n=45; n=17 females; age: 48+/-15 years) and from n=12 donor hearts (controls) by a human observer (baseline vs. enhanced expression) and quantitatively by a digital image analysis (DIA) system. The DIA-measured qualities were area fraction (AF), surface-volume ratio (SVR) and integral optical density (ID). The sICAM-1 levels of the DCM patients and n=12 healthy volunteers (controls) were measured by ELISA (means of duplicate measurements). Intramyocardial ICAM-1 expression and sICAM-1 levels were compared in these DCM patients. RESULTS: Of the DCM patients, n=24 (53%) demonstrated statistically higher sICAM-1 levels compared to controls (>198 ng/ml). By semiquantitative and quantitative DIA evaluation, endothelial ICAM-1 abundance was present in n=25 (56%) of the DCM biopsies. sICAM-1 correlated significantly (P<0.001) both with the semiquantitatively assessed and the DIA-measured ICAM-1-AF, the ICAM-1-SVR and the ICAM-1-ID. The positive predictive value of sICAM-1 measurements for intramyocardial ICAM-1 abundance was 96%, and the negative predictive value was 71%, with a receiver operating characteristic area under the curve of 0.93. Furthermore, sICAM-1 levels correlated with intramyocardial T-lymphocytic (CD2+/CD3+) infiltrates (P<0.03). CONCLUSIONS: Measurement of non-invasively obtained sICAM-1 reliably reflects intramyocardial ICAM-1 expression and may therefore serve as a non-invasive marker of inflammatory activity in DCM.     

Clinical and biochemical spectrum of metabolic cardiomyopathy in Egyptian children

BackgroundInborn errors of metabolism (IEMs) commonly present with pediatric cardiomyopathy. Identification of the underlying cause is necessary as it may lead to improved outcomes.ObjectivesWe aimed to investigate the diagnostic rate, the clinical, and biochemical spectra of IEMs among Egyptian pediatric patients presenting with cardiomyopathy, and their outcome measures.MethodsWe retrospectively analyzed the clinical, biochemical, and radiological data of 1512 children diagnosed with cardiomyopathy at Cairo University Children''s Hospital over a 5-year duration.ResultsTwo hundred twenty-nine children were clinically suspected as IEMs and underwent metabolic workup. Nineteen different IEMs were confirmed in 57 (24.4%) of the suspected children. Their median age at presentation was 2.6 years and the majority had extra-cardiac manifestations. Hypertrophic cardiomyopathy represented 43/57 (75.4%) of confirmed cases, while dilated cardiomyopathy represented 13/57 (22.8%), and one patient presented with a mixed phenotype. Twenty- six patients (45.6%) survived, while 31 patients (54%) either died or were lost to follow up and assumed deceased.ConclusionsWe developed for the first time a database and a diagnostic scheme for metabolic cardiomyopathies in Egyptian children. With the recent introduction of enzyme replacement therapy, many metabolic disorders became treatable, thus establishing an early and accurate diagnosis is extremely important.     

Randomized, double-blind study of the analgesic efficacy of morphine-6-glucuronide versus morphine sulfate for postoperative pain in major surgery

BACKGROUND: Morphine-6-glucuronide (M6G) has promising preclinical characteristics and encouraging pharmacokinetic features for acute nociceptive pain. Early studies have produced a good safety profile when compared to morphine sulfate, although in surrogate pain models studies, a mixed picture emerged. A study to evaluate the efficacy and safety profile in a clinical setting was designed. METHODS: The authors conducted a double-blind, randomized, dose-finding study of patients scheduled to undergo major joint replacement. One hundred patients of both sexes were included, with 50 patients in each group. A loading dose of 10 mg of study medication was given intravenously at induction of anesthesia, and two further doses were allowed during surgery if required. Bolus doses via a patient-controlled analgesia system were given subcutaneously at 2 mg/dose and set at a 10-min lockout. Assessments of pain intensity and relief were recorded during the 24-h period. RESULTS: There were no statistically significant differences between the treatments for 24-h mean pain intensity. However, pain intensity was significantly higher in the M6G group than in the morphine group at 30 min and 1 h. There was no statistical difference in 24-h mean pain relief or retrospective pain scores at any time point during the 24-h period. The severity of sedation was significantly greater in the morphine group than in the M6G group at 30 min, 1 h, 2 h, and 24 h. Respiratory depression was greater in the morphine group than in the M6G group, and more patients in the morphine group withdrew from the study because of respiratory depression. CONCLUSIONS: Overall, M6G has an analgesic effect similar to that of morphine over the first 24 h postoperatively. However, M6G may be slower onset initially than morphine; therefore, a larger initial dose may be required.     

Comparison of the morphologic and vascular reactivity of the proximal and distal radial artery

Background. Variations in the morphology and vascular reactivity of the proximal and distal radial artery might influence its performance as a bypass conduit.

Methods. The morphologic and functional characteristics of the proximal and distal RAs were compared with those of the left and right internal mammary arteries by using histologic and in vitro organ bath techniques.

Results. Proximal RA had a significantly greater medial cross-sectional area compared with that of the distal RA (2.48 ± 0.27 mm² compared with 1.86 ± 0.21 mm², p < 0.05), which were both significantly greater than the left internal mammary artery (0.54 ± 0.09 mm²) or the right internal mammary artery (0.67 ± 0.03 mm²). Proximal RA had a significantly greater response to 90 mmol/L potassium chloride than that of distal RA (88.4 ± 7.3 compared with 60.2 ± 10.3 mN, p < 0.05), and both contracted more than the left internal mammary artery (30.3 ± 2.9 mN) and the right internal mammary artery (32.6 ± 4.1 mN). There was no difference in the response to noradrenaline and adrenaline between proximal and distal RA, both of which contracted more than the left and right internal mammary arteries.

Conclusions. When choosing a segment of RA for use as a bypass conduit, regional variations in biologic properties should be considered.