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INSIDE THIS ISSUE

Inside This Issue

	State-of-the-Art Paper

Top State-of-the-Art Paper Clinical Research

Charalambos Antoniades, Constantinos Bakogiannis, Dimitris Tousoulis, Alexios S. Antonopoulos, Christodoulos Stefanadis

Antoniades and colleagues review the evidence linking the CD40/CD40 ligand (CD40L) system to cardiovascular risk, which is currently a topic of intensive research. CD40L and the soluble form of the receptor, sCD40L, belong to the tumor necrosis factor superfamily and are both prothrombotic and proinflammatory. sCD40L has multiple autocrine, paracrine, and endocrine actions, and it may trigger key mechanisms precipitating atherothrombosis. While several conventional cardiovascular medications, such as antiplatelet therapy, statins, and angiotensin-converting enzyme inhibitors, reduce sCD40L, it is unclear if agents designed specifically to target CD40/CD40L will reduce cardiovascular risk.

	Clinical Research

Top State-of-the-Art Paper Clinical Research

 
Interventional Cardiology.   Prasugrel Improves Outcomes Over Clopidogrel Regardless of Glycoprotein IIb/IIIa Inhibitor Use
678

Michelle O'Donoghue, Elliott M. Antman, Eugene Braunwald, Sabina A. Murphy, P. Gabriel Steg, Ariel Finkelstein, William F. Penny, Viliam Fridrich, Carolyn H. McCabe, Marc S. Sabatine, Stephen D. Wiviott

Prasugrel is a rapidly-acting thienopyridine that reduces ischemic events compared with clopidogrel in patients with acute coronary syndromes undergoing percutaneous intervention, although with increased bleeding. This subgroup analysis evaluated the impact of concomitant use of a glycoprotein (GP) IIb/IIIa inhibitor. Approximately one-half of the subjects in the TRITON–TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis In Myocardial Infarction 38) trial received a GP IIb/IIIa inhibitor, based on physician discretion. Prasugrel significantly reduced the risk of ischemic events irrespective of GP IIb/IIIa inhibitor use. Prasugrel did increase the bleeding risk compared to clopidogrel, but combined treatment with a GP IIb/IIIa did not alter the relative increased risk of bleeding. The use of GP IIb/IIIa inhibitors does not alter the relative risks or benefits of prasugrel compared with clopidogrel.

Valvular Heart Disease.   Initial Results With the MitraClip Device

686

Ted Feldman, Saibal Kar, Michael Rinaldi, Peter Fail, James Hermiller, Richard Smalling, Patrick L. Whitlow, William Gray, Reginald Low, Howard C. Herrmann, Scott Lim, Elyse Foster, Donald Glower, for the EVEREST Investigators

The MitraClip device (Evalve Inc., Menlo Park, California) is designed to reduce mitral regurgitation (MR) by creating a double orifice by connecting the central portion of the 2 leaflets with a metal clip. Feldman and colleagues describe the safety and midterm efficacy results of over 100 patients treated with the device. Ten patients (9%) had a major adverse event, including a single death. There were no incidences of clip embolization, although the clip did detach from a single leaflet in 9% of subjects. Overall acute procedural success was 76%, with most of these patients having 1+ or less MR. For the subjects who subsequently required open surgery after a clip procedure, there was no evidence that the procedure made the valve "nonrepairable." Percutaneous repair with the MitraClip appears promising with low morbidity and mortality.

Arterial Reflections and Stiffness.   Increased Pulse Pressure Caused by Increased Wave Reflections in Women

695

Marina Cecelja, Benyu Jiang, Karen McNeill, Bernet Kato, James Ritter, Tim Spector, Phil Chowienczyk

Central pulse pressure (cPP) is augmented above the first systolic shoulder of the central arterial pulse (P1) by pressure waves reflected from the periphery of the circulation. Cecelja and colleagues sought to determine the relative contributions of P1 and the augmentation pressure (Paug) to cPP, and the causes of higher Paug in women. P1 and Paug accounted for 22% and 76%, respectively, of the variance in cPP. P1 was positively correlated with pulse wave velocity, whereas Paug was negatively correlated with the ratio of the diameter of the femoral artery to that of the abdominal aorta. These results suggest that, in women, Paug is the major determinant of cPP and might be caused by relatively small femoral arteries.

Arterial Reflections and Stiffness.   Slow Heart Rates Increase Pressure Reflection Waves, Increase Central Aortic Pressure

705

Bryan Williams, Peter S. Lacy, for the CAFE and the ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) Investigators

This analysis sought to determine why atenolol was less effective at reducing cardiovascular events compared with an amlodipine-based regimen. Central pressures were derived from brachial pressure and radial pulse wave analysis in over 2,000 subjects with more than 7,000 measurements over 4 years. There was no impact of heart rate on brachial systolic or brachial pulse pressures; however, slower heart rates did correlate with higher central aortic systolic and central pulse pressures. Further analysis showed a strong inverse relationship between heart rate and augmentation index, suggesting increased wave reflection at lower heart rates. These findings indicate that heart rate reduction with beta-blockers is a major mechanism accounting for less effective central aortic pressure reduction per unit change in brachial pressure.

Editorial Comment: Michael F. O'Rourke, Christopher S. Hayward, p. 714

Obesity and the Heart.   Weight Loss Decreases LV Mass, Improves Filling Parameters

718

Oliver J. Rider, Jane M. Francis, Mohammed K. Ali, Steffen E. Petersen, Monique Robinson, Matthew D. Robson, James P. Byrne, Kieran Clarke, Stefan Neubauer

Obese patients have higher rates of left ventricular hypertrophy (LVH), but it is not clear if the LVH results solely from obesity or from related conditions, such as hypertension, diabetes, or hypercholesterolemia. Rider and colleagues studied the effects of substantial weight loss over 1 year in obese subjects without other risk factors for LVH. Thirty-seven obese (body mass index 40 kg/m²) and 20 normal-weight subjects underwent cardiac magnetic resonance imaging. Thirty of the obese subjects underwent repeat imaging after 1 year of significant weight loss, achieved by diet or bariatric surgery. Left ventricular (LV) and right ventricular mass were significantly increased in the obese; LV diastolic function and aortic distensibility were also impaired. Both diet and bariatric surgery led to comparable improvements in these parameters. LVH can be caused solely by obesity and can regress with weight loss.

Editorial Comment: Elie Mousseaux, p. 727

Pediatric Cardiology.   Extracorporeal Membrane Oxygenation Is Effective for Early Failure After Pediatric Heart Transplantation
730

Cecile Tissot, Shannon Buckvold, Christina M. Phelps, D. Dunbar Ivy, David N. Campbell, Max B. Mitchell, Suzanne Osorio da Cruz, Bill A. Pietra, Shelley D. Miyamoto

This paper describes the use of extracorporeal membrane oxygenation (ECMO) to support pediatric patients who either fail to wean from cardiopulmonary bypass after heart transplantation or develop hemodynamic instability within the first few days after transplantation. Tissot and colleagues reviewed the records of over 300 patients who underwent transplantation, of whom 28 (9%) required ECMO. The median age was 0.3 years and the median weight was 4.5 kg. Approximately one-half of patients were successfully weaned off of ECMO and discharged alive, with a mean duration of ECMO of 2.8 days for survivors. Of the patients who survived the index hospitalization, 100% were alive 3 years later. ECMO appears to be useful by providing temporary support in the immediate post-operative period after pediatric heart transplantation.

Editorial Comment: Carl Lewis Backer, p. 738

Related Articles

The CD40/CD40 Ligand System: Linking Inflammation With Atherothrombosis

Charalambos Antoniades, Constantinos Bakogiannis, Dimitris Tousoulis, Alexios S. Antonopoulos, and Christodoulos Stefanadis
J. Am. Coll. Cardiol. 2009 54: 669-677. [Abstract] [Full Text] [PDF]

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