1665

Shelby Kutty, Partho P. Sengupta, Bijoy K. Khandheria

The patent foramen ovale (PFO) is a normal interatrial communication during fetal life that persists after birth in approximately 1 in every 4 adults. Though there is compelling circumstantial evidence implicating PFO as a route for embolic transit from the systemic circulation to the brain, the precise role of PFO in the pathogenesis of cryptogenic stroke is not yet established. Several randomized trials of transcatheter PFO closure versus medical management are ongoing, but to date there is no clear benefit to either strategy. Other trials have shown equivalency for anticoagulation and antiplatelet therapies.

1672

Timothy A. Fairbairn, David M. Meads, Adam N. Mather, Manish Motwani, Sue Pavitt, Sven Plein, Daniel J. Blackman, John P. Greenwood

Health-related quality of life (HRQOL) is an important outcome measure, for which there is limited evidence in transcatheter aortic valve implantation (TAVI) populations. Fairbairn and colleagues administered 2 HRQOL questionnaires at baseline, 30 days, 6 months, and 12 months after TAVI to 102 subjects. HRQOL significantly improved over 12 months at which time it was similar to age-adjusted U.S. population norms. The greatest change occurred from baseline to 30 days. HRQOL significantly improves early following TAVI and is maintained out to at least 1 year.

1681

Antonio Tello-Montoliu, Salvatore D. Tomasello, José Luis Ferreiro, Masafumi Ueno, Naveen Seecheran, Bhaloo Desai, Murali Kodali, Ronald K. Charlton, Lyndon C. Box, Martin M. Zenni, Luis A. Guzman, Theodore A. Bass, Dominick J. Angiolillo

Tello-Montoliu and colleagues calculated the pharmacodynamic (PD) effects of different prasugrel loading doses in patients on chronic prasugrel therapy. This was a prospective PD study in 64 patients on maintenance prasugrel therapy (10 mg/day) randomized to a 10-mg, 30-mg, or 60-mg dose of prasugrel. The 60-mg dose reduced the platelet reactivity index after 1 and 4 h, and was superior to either 30 mg or 10 mg at 4 h. Similar results were obtained with other P2Y12 specific assays. In patients on maintenance prasugrel therapy, reloading with a 60-mg dose should be considered prior to percutaneous coronary intervention.

1688

Gail A. Laughlin, Kevin Cummins, Christina L. Wassel, Lori B. Daniels, Joachim H. Ix

Fetuin-A acts as an inhibitor of calcification by increasing the blood solubility of calcium and phosphorus. It also binds directly to the insulin receptor and induces insulin resistance. In this population-based prospective study of 633 men and 1,025 women, fetuin-A levels and cardiovascular disease (CVD) risk factors were measured in 1992 to 1996 and the subjects were followed for vital status through 2010. The association of fetuin-A with CVD mortality differed by diabetes status; for participants without diabetes, the risk of CVD mortality was highest for those in the lowest quartile. For participants with diabetes, the opposite was true with risk of CVD mortality being lowest for those in the lowest quartile.

1697

Michelle Melone, Larissa Wilsie, Oksana Palyha, Alison Strack, Shirya Rashid

Serum levels of the adipose tissue adipokine, resistin, are increased in human obesity and have been linked to cardiovascular risk. Melone and colleagues investigated the role resistin plays in regulating the uptake of atherogenic low-density lipoproteins (LDL) in human hepatocytes. In a series of experiments using cultured human hepatocytes, resistin downregulated hepatocyte LDL receptor expression by 40%. This was at least partially due to increased expression of the protease, PCSK9, which enhances intracellular LDL receptor degradation. These results, suggesting that lowering resistin levels or blocking its effects, should be considered as a method for reducing LDL levels, particularly in obese patients.

Editorial Comment: Sergio Fazio, MacRae F. Linton, page1706

1709

Elisabet Zamora, Josep Lupón, Joan Vila, Agustín Urrutia, Marta de Antonio, Hèctor Sanz, Maria Grau, Jordi Ara, Antoni Bayés-Genís

There are 3 widely formulas used for calculating estimated glomerular filtration rate (eGFR): Cockroft-Gault formula, Modification of Diet in Renal Disease Study-4, and the Chronic Kidney Disease Epidemiology Collaboration. Zamora and colleagues compared the utility of these 3 formulas for predicting the risk of death in ambulatory patients with systolic heart failure. A total of 925 patients with a mean left ventricular ejection fraction of 31% were studied with a mean follow-up of 3.5 years. All 3 formulas afforded independent prognostic information, but risk prediction was most accurate using the Cockroft-Gault formula with a net reclassification improvement of 21%. The Cockroft-Gault formula [(140 − age in years) × weight in kilograms/(72 × serum creatinine level in mg/dl) adjusted by sex (× 0.85 in women) and indexed to body surface area] provides the most useful prognostic information relating eGFR to mortality.

Editorial Comment: Robert W. Schrier, Dmitri Shchekochikhin, page1716

1719

Caroline Jaarsma, Tim Leiner, Sebastiaan C. Bekkers, Harry J. Crijns, Joachim E. Wildberger, Eike Nagel, Patricia J. Nelemans, Simon Schalla

Jaarsma and colleagues performed a meta-analysis to determine the diagnostic accuracy of single-photon emission computed tomography (SPECT), cardiac magnetic resonance (CMR), and positron emission tomography (PET) perfusion imaging. A total of 166 articles compared the diagnostic performance for detecting a (≥50% diameter stenosis) on coronary angiography. Patient-based analysis demonstrated similar sensitivities for SPECT, CMR, and PET with specificities of 61%, 76%, and 81%, respectively. The diagnostic odds ratio were 15.3, 26.4, and 36.5, respectively. In summary, all 3 modalities have high sensitivity, but PET has the highest diagnostic performance. The authors conclude that referring physicians should consider these findings in the context of local expertise and infrastructure.