J. Voss

Pharmacogenetic testing for clopidogrel using the rapid INFINITI analyzer: a dose-escalation study.

OBJECTIVES Our aim was to assess whether a higher clopidogrel maintenance dose has a greater antiplatelet effect in CYP2C19*2 allele carriers compared with noncarriers. BACKGROUND Clopidogrel is a prodrug that is biotransformed by the cytochrome P450 enzymes CYP2C19, 2C9, and 3A4, 2B6, 1A2. The CYPC219*2 loss of function variant has been associated with a reduced antiplatelet response to clopidogrel and a 3-fold risk of stent thrombosis. METHODS Forty patients on standard maintenance dosage clopidogrel (75 mg), for 9.4 +/- 9.2 weeks, were enrolled into a dose escalation study. Platelet function was assessed at baseline and after 1 week of 150 mg once daily using the VerifyNow platelet function analyzer (Accumetrics Ltd., San Diego, California). Genomic DNA was hybridized to a BioFilmChip microarray on the INFINITI analyzer (AutoGenomics Inc., Carlsbad, California) and analyzed for the CYP19*2, *4, *17, and CYP2C9*2, *3 polymorphisms. RESULTS Platelet inhibition increased over 1 week, mean +8.6 +/- 13.5% (p = 0.0003). Carriers of the CYP2C19*2 allele had significantly reduced platelet inhibition at baseline (median 18%, range 0% to 72%) compared with wildtype (wt) (median 59%, range 11% to 95%, p = 0.01) and at 1 week (p = 0.03). CYP2C19*2 allele carriers had an increase in platelet inhibition of (mean +9 +/- 11%, p = 0.03) and reduction in platelet reactivity (mean -26 +/- 38 platelet response unit, p = 0.04) with a higher dose. Together CYP2C19*2 and CYP2C9*3 loss of function carriers had a greater change in platelet inhibition with 150 mg daily than wt/wt (+10.9% vs. +0.7%, p = 0.04). CONCLUSIONS Increasing the dose of clopidogrel in patients with nonresponder polymorphisms can increase antiplatelet response. Personalizing clopidogrel dosing using pharmacogenomics may be an effective method of optimizing treatment.

Frequency and sequelae of retained implanted cardiac device material post heart transplantation.

Cardiac implantable electronic devices (CIEDs) have now become common therapeutic adjuncts for patients prior to orthotopic heart transplantation (OHT). Removal of the generator and the intracardiac components occurs at time of transplantation but removal of the intravascular portion of leads may be unsuccessful without specialized extraction equipment.

Characteristics and Outcomes for Right Heart Endocarditis: Six-year Cohort Study

Right heart endocarditis makes up 5-10% of all infective endocarditis involving valvular, congenital and artificial structures. Given the limited literature in this area, we reviewed the characteristics, management and outcomes of this condition in this retrospective cohort study. Thirty-five patients with right heart endocarditis admitted to Auckland City Hospital during 2005-2010 were followed-up for 3.4+/-2.5 years. In-hospital mortality was 11.4% (4), all occurring in those treated medically (20.0% (4) vs 0.0% (0), P=0.119). Surgical intervention was independently associated with reduced long-term mortality (HR 0.078, 95%CI 0.010-0.609, P=0.015) in multivariate analysis, while concurrent left heart endocarditis predicted both in-hospital mortality (HR 11.0, 95%CI 1.18-102, P=0.027) and long-term mortality (HR 3.20, 95%CI 1.03-9.92, P=0.044). Our study showed that surgical intervention and concomitant left heart endocarditis are positive and negative prognostic factors for outcomes after right heart endocarditis.

Valvular repair or replacement for mitral endocarditis: 7-year cohort study.

Background A few studies have compared mitral valve repair and replacement in the setting of infective endocarditis, with varying results. We compared the characteristics and outcomes of mitral repair and replacement in endocarditis patients. Methods All patients undergoing mitral valve repair or replacement for active mitral endocarditis during 2005–2011 were included. Operative and follow-up mortality, composite morbidity, recurrent endocarditis, and redo operations were prespecified endpoints for analyses. Results There were 25 and 35 patients undergoing mitral valve repair and replacement, respectively. They were followed-up for 3.9 ± 2.5 years. Valve replacement patients were older (p = 0.029), had a higher prevalence of intracardiac abscess (p = 0.035), previous endocarditis (p = 0.036), atrial fibrillation (p = 0.001), worse renal function (p = 0.013), higher risk scores (p = 0.004–0.020), and longer operation times (p < 0.001). Repair and replacement had similar rates of operative mortality (4.0% vs. 8.6%, p = 0.634), composite morbidity (16.0% vs. 28.6%, p = 0.357), survival (p = 0.564), recurrent endocarditis (p = 0.081), and redo operations (p = 0.813). Independent predictors of operative mortality were preoperative inotropic or intraaortic balloon pump support. The independent predictor of mortality during follow-up was dialysis. Independent predictors of composite morbidity were intracardiac abscess and hypercholesterolemia. The independent predictor of recurrent endocarditis was previous endocarditis, and the independent predictor of redo operation was previous stroke. Conclusion Mitral valve replacement candidates had more baseline risk factors and higher raw rates of postoperative mortality and morbidity, which did not reach statistical significance.

Seven-year Cohort Study of Valvular Repair or Replacement for Active Mitral Endocarditis

of disease in the LAD was seen in 11% at 10 years, with a mean time to angiography of 7.3 years. Conclusion: The use of composite SV-IMA grafts in this group of patients provided good late survival and freedom from reintervention. Atheromatous disease in the venous segmentwasuncommondespite followupbeyond 15 years. The incidence of development of significant LAD disease after surgery for non-LAD double vessel disease was low. http://dx.doi.org/10.1016/j.hlc.2013.05.569