BACKGROUND:Idiopathic dilated cardiomyopathy is often familial, and apparently healthy relatives may have latent, early, or undiagnosed established disease.OBJECTIVE:To determine the prevalence and natural history of asymptomatic cardiac abnormalities among sampled relatives of unselected patients referred for management of dilated cardio-myopathy.DESIGN:Prospective cohort study.PATIENTS:767 asymptomatic relatives of 189 consecutive unselected patients with dilated cardiomyopathy.MEASUREMENTS:Clinical evaluation, including history, physical examination, electrocardiography, and echocardiography, was performed. Participants were classified in accordance with published echocardiographic criteria. Sampled relatives who did not have evidence of dilated cardiomyopathy at the initial evaluation were followed for a median of 57 months (range, 1 to 133 months).RESULTS:Of the 767 patients evaluated, 592 (77.2%) were assessed as healthy, 35 (4.6% [95% CI, 3.7% to 7.6%]) had dilated cardiomyopathy, 119 (15.5% [CI, 12.5% to 18.8%]) had left ventricular enlargement without systolic dysfunction, and 21 (2.7% [CI, 1.9% to 4.9%]) had depressed fractional shortening without ventricular dilatation. At follow-up, progression to dilated cardiomyopathy occurred in 13 (10%) relatives with left ventricular enlargement or depressed fractional shortening versus 3 (1.3%) healthy relatives. In a multivariate model, only left ventricular enlargement or depressed fractional shortening independently predicted progression to dilated cardiomyopathy (hazard ratio, 10.0 [CI, 2.8 to 35.5]; P < 0.001).LIMITATIONS:Because relatives had to be willing to participate and be available geographically, selection bias may have occurred.CONCLUSION:Treatable asymptomatic dilated cardiomyopathy was identified in 4.6% of asymptomatic relatives. In addition, left ventricular enlargement and depressed fractional shortening were common in asymptomatic relatives of patients with dilated cardiomyopathy and were associated with a statistically significant medium-term risk for disease progression. Evaluation of relatives of patients with cardiomyopathy is recommended.

The internal pool of GPIIb/IIIa, which is expressed upon platelet activation, may be inaccessible to inhibition by GPIIb/IIIa antagonists. To determine the occupancy of the internal and external pools of GPIIb/IIIa and platelet function following an abciximab bolus and infusion, 15 patients undergoing elective percutaneous transluminal coronary angioplasty were administered abciximab as a bolus and 36-h infusion. GPIIb/IIIa receptor number and occupancy in resting and TRAP-6 (20 microM)-activated samples (to expose the internal pool of GPIIb/IIIa) was quantified using a monoclonal antibody-based assay. Antibody binding was quantified by flow cytometry and platelet inhibition by light transmittance aggregation and by the rapid platelet function analyser (Accumetrics, San Diego, CA). The target of >80% receptor occupancy (range 82--99% occupancy) of the external pool of GPIIb/IIIa was achieved in all patients at 3 min. Receptor occupancy of the combined internal and external pools of GPIIb/IIIa was less, ranging from 75 to 93% and again was maximal at 3 min. Platelet aggregation was markedly inhibited to 20 microM ADP (maximal, 11 +/- 2% of baseline), but less so to 5 microM TRAP-6 (maximal, 36 +/- 25% of baseline). Following discontinuation of the drug, there was a gradual fall in receptor occupancy over 15 days coinciding with the disappearance of abciximab from the platelet surface. Maximum inhibition of platelet function and receptor occupancy of the external pool of GPIIb/IIIa occurs within 3 min of an abciximab bolus and infusion. However, some internal receptors that are expressed by potent agonists are not occupied, which may explain the incomplete inhibition of platelet aggregation.

OBJECTIVESThis study was designed to document the inflammatory response up to one year after acute presentation with unstable angina (UA) and non–Q wave infarction (NQMI) as reflected by the expression of soluble cell adhesion molecules (CAMs).BACKGROUNDCoronary plaque inflammation is a key component in the pathogenesis of acute coronary syndromes. Cell adhesion molecules are critical mediators of the inflammatory process. Soluble forms of these molecules are detectable in serum and are elevated acutely in patients with UA and NQMI.METHODSPatients presenting with UA and NQMI had serum samples taken at presentation and then after three, six and 12 months. A control group of similar age and gender distribution was used for comparison. Levels of soluble inter-cellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial-selectin and platelet-selectin were measured using an ELISA technique.RESULTSWe studied 91 patients (M/F = 73/18, mean age 62 ± 11 years, 56 UA and 35 NQMI) and 24 controls (M/F = 18/6, mean age 56 ± 12 years). Levels of all four soluble CAMs were significantly elevated in both UA and NQMI patients at presentation, three and six months in comparison with controls. Levels in UA and NQMI groups fell between six and 12 months after initial presentation.CONCLUSIONSThe results suggest that the inflammatory stimulus triggering expression of CAMs is sustained for up to six months after presentation with either UA or NQMI and then returns toward control values over the following six months.