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INSIDE THIS ISSUE

Inside This Issue

	State-of-the-Art Paper

Top State-of-the-Art Paper Clinical Research Pre-Clinical Research News from the NHLBI Expedited Publication

Jeffrey S. Berger, Courtney O. Jordan, Donald Lloyd-Jones, Roger S. Blumenthal

Risk-stratifying asymptomatic patients for cardiovascular disease remains challenging, particularly for those with low or intermediate short-term risk. Berger and colleagues review 6 of the currently available risk algorithms including the end points, the population in which it was derived and/or validated, the variables included, and the limitations. Several areas of uncertainty remain including the utility of 10-year versus lifetime risk, whether it is more useful to try to predict cardiovascular disease or coronary heart disease end points, and the age at which to start assessments. The conclusion is that the best approach is to routinely perform a risk score assessment with each patient, including discussion of the global cardiovascular risk and lifetime risk.

	Clinical Research

Top State-of-the-Art Paper Clinical Research Pre-Clinical Research News from the NHLBI Expedited Publication

 
Interventional Cardiology.   Stent Overlap Linked to Worse Outcomes

1178

Lorenz Räber, Peter Jüni, Lukas Löffel, Simon Wandel, Stéphane Cook, Peter Wenaweser, Mario Togni, Rolf Vogel, Christian Seiler, Franz Eberli, Thomas Lüscher, Bernhard Meier, Stephan Windecker

Räber and colleagues compared the angiographic and long-term clinical outcome between patients with and without overlap of drug-eluting stents (DES). Over 1,000 subjects enrolled in the SIRTAX (Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization) trial were divided according to the presence or absence of stent overlap and number of stents per vessel: 13% had multiple DES in a vessel with overlap, 20% had multiple DES in a vessel without overlap, and the remaining 67% had a single DES per vessel. Angiographic follow-up showed an increased late loss in DES overlap patients compared with the other groups and the smallest mean luminal diameter was located at the zone of stent overlap. Major adverse cardiac events were more common in patients with overlap. DES overlap appears to be frequent and may be associated with impaired angiographic and long-term clinical outcome.

Myocardial Infarction.   Ranolazine May Be Beneficial in ACS Patients With Elevated BNP

1189

David A. Morrow, Benjamin M. Scirica, Marc S. Sabatine, James A. de Lemos, Sabina A. Murphy, Petr Jarolim, Pierre Theroux, Christophe Bode, Eugene Braunwald

Because ranolazine is believed to reduce ventricular wall stress, B-type natriuretic peptide (BNP), which rises in response to wall stress, may identify those patients most likely to benefit from treatment. Morrow and colleagues tested this hypothesis with samples collected from the MERLIN–TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST Elevation Acute Coronary–Thrombolysis In Myocardial Infarction 36) trial which randomized subjects with acute coronary syndromes (ACS) to either ranolazine or placebo. Subjects with BNP >80 pg/ml were at significantly higher risk of the primary end point at 1 year. In these patients, ranolazine reduced the primary end point (hazard ratio: 0.79), while there was no detectable effect in those with BNP <80 pg/ml. These findings indicate that ranolazine may be beneficial in high-risk patients with ACS identified by elevated BNP.

Editorial Comment: Steven P. Marso, p. 1197

Myocardial Infarction.   Cyclosporine Prior to Angioplasty May Safely Reduce Infarct Size
1200

Nathan Mewton, Pierre Croisille, Gerald Gahide, Gilles Rioufol, Eric Bonnefoy, Ingrid Sanchez, Thien Tri Cung, Catherine Sportouch, Denis Angoulvant, Gérard Finet, Xavier André-Fouët, Geneviève Derumeaux, Christophe Piot, Hélène Vernhet, Didier Revel, Michel Ovize

The rationale for this proof-of-concept study was that cyclosporine is a potent inhibitor of the opening of the mitochondrial permeability transition pore, which plays a crucial role in reperfusion injury. Mewton and colleagues randomized 28 patients with acute myocardial infarction to receive a single dose of cyclosporine or placebo at the time of reperfusion. Cardiac magnetic resonance imaging was performed 5 days and 6 months later. Infarct size was reduced at 6 months in the cyclosporine group compared with the control group. This was associated with a significant reduction of left ventricular end-systolic volume both at day 5 and at 6 months after infarction. There was no evidence of an effect on remote, noninfarcted myocardium. These early results suggest that cyclosporine, injected prior to reperfusion, can reduce infarct size without detrimental cardiac effects.

Editorial Comment: Nathaniel Reichek, Kambiz Parcham-Azad, p. 1206

Lipid Disorders.   Atorvastatin Decreases Insulin Sensitivity

1209

Kwang Kon Koh, Michael J. Quon, Seung Hwan Han, Yonghee Lee, Soo Jin Kim, Eak Kyun Shin

Clinical trials suggest that some statin treatments may increase the incidence of diabetes. Koh and colleagues investigated whether atorvastatin decreases insulin sensitivity and increases ambient glycemia in hypercholesterolemic patients by randomizing subjects to varying doses of atorvastatin or placebo for 2 months. Atorvastatin significantly increased fasting plasma insulin and glycated hemoglobin levels and decreased insulin sensitivity. Atorvastatin treatment, despite lowering low-density lipoprotein cholesterol, may cause insulin resistance in hypercholesterolemic patients.

Heart Rhythm Disorders.   Immediate Changes Seen in Atrial EP Properties After Mitral Commissurotomy

1217

Bobby John, Martin K. Stiles, Pawel Kuklik, Anthony G. Brooks, Sunil T. Chandy, Jonathan M. Kalman, Prashanthan Sanders

John and colleagues studied the effect of chronic stretch on the electrophysiological (EP) characteristics of the atria. Subjects with mitral stenosis undergoing mitral commissurotomy (MC) underwent detailed EP studies of the right and left atria before and after the procedure. Immediately after MC, there was a significant decrease in left atrial volume and pressure. This was associated with a reduction in P-wave duration, and increases in conduction velocity and voltage. The electrophysiologic and electroanatomic abnormalities that result from chronic atrial stretch and seem to predispose to atrial fibrillation, may resolve almost immediately when the atrial pressure is reduced.

Radiation Injury.   Prolonged NF-B Activation May Underlie Radiation Induced Cardiac Events
1227

Martin Halle, Anders Gabrielsen, Gabrielle Paulsson-Berne, Caroline Gahm, Hanna Agardh, Filip Farnebo, Per Tornvall

Recent studies have shown that radiotherapy is associated with cardiovascular disease years after treatment. Halle and colleagues investigated gene expression networks in previously radiated human arteries and compared them to arteries from a nonradiated site in subjects undergoing cancer reconstruction surgery, 4 to 500 weeks after radiation treatment. The arterial biopsies were compared, using Affymetrix (Santa Clara, California) microarrays. Thirteen genes were synchronously expressed in all radiated segments at levels higher or lower than nonradiated segments. Most of the differentially regulated genes related to the nuclear factor-kappa B (NF-B) signaling pathway. NF-B activation was confirmed by immunohistochemistry and immunofluorescence. The observed sustained inflammatory response may be provoked by deoxyribonucleic acid injury and may explain cardiovascular disease years after radiation.

Editorial Comment: Neal L. Weintraub, W. Keith Jones, David Manka, p. 1237

	Pre-Clinical Research

Top State-of-the-Art Paper Clinical Research Pre-Clinical Research News from the NHLBI Expedited Publication

 
Pre-Clinical Research.   Molecular Imaging Shows Minocycline Inhibits MMP Activity in Atherosclerotic Plaques

1240

Satoru Ohshima, Shinichiro Fujimoto, Artiom Petrov, Hironori Nakagami, Nezam Haider, Jun Zhou, Nobuhiro Tahara, Mariana Kiomy Osako, Ai Fujimoto, Jie Zhu, Toyoaki Murohara, D. Scott Edwards, Navneet Narula, Nathan D. Wong, Y. Chandrashekhar, Ryuichi Morishita, Jagat Narula

Matrix metalloproteinase (MMP) activity may contribute to plaque instability and is a potential therapeutic target for plaque stabilization. Ohshima and colleagues used a broad spectrum matrix metalloproteinase inhibitor (MPI) labeled with technetium to noninvasively quantify MMP activity in atherosclerotic plaques, and the effect of treatment with fluvastatin (FS) and minocycline (MC) on MMP activity. Atherosclerotic lesions were produced in rabbits who were then treated with either FS, low-dose MC, high-dose MC, a combination of MC and FS, or no intervention for 4 months. MPI uptake was highest in the control animals and was significantly lower in each of the active treatment groups. Histological analysis confirmed the visualized findings. This imaging technique may be a useful surrogate for studying the efficacy of MMP-targeted interventions.

Pre-Clinical Research.   Extracellular Matrix Isolated From the Pig Small Intestine May Promote Post-MI Recovery
1250

Zhi-Qing Zhao, John D. Puskas, Di Xu, Ning-Ping Wang, Mario Mosunjac, Robert A. Guyton, Jakob Vinten-Johansen, Robert Matheny

This study tested the hypothesis that injecting small intestine extracellular matrix emulsion (EMU) directly into the myocardium would stimulate the recruitment of positive factors after myocardial infarction. Sixty-four rats were subjected to 45 min of ischemia followed by reperfusion; saline or EMU was directly injected into the area at risk myocardium after reperfusion. The population of c-kit–positive cells, alpha-smooth muscle actin–expressing myofibroblasts and macrophages in the infarcted myocardium were all significantly increased after EMU injection. Angiogenesis in the EMU area was also enhanced and echocardiography showed significant improvements in the EMU group. Injection of EMU into the infarcted myocardium appears to increase neovascularization and preserve cardiac function.

	News from the NHLBI

Top State-of-the-Art Paper Clinical Research Pre-Clinical Research News from the NHLBI Expedited Publication

 
News from the NHLBI.   The NHLBI Bench to Bassinet Program
1262

Jonathan R. Kaltman, Charlene Schramm, Gail D. Pearson

To accelerate the discoveries that may lead to improved clinical outcomes for children with congenital heart disease (CHD), the National Heart, Lung, and Blood Institute has launched a novel translational research program, the Bench to Bassinet program. Kaltman and colleagues describe the Bench to Bassinet program in this report. It is composed of 3 entities. The Cardiovascular Development Consortium, which will attempt to elucidate the regulatory and developmental derangements that cause CHD. The Pediatric Cardiac Genomics Consortium's goals are to delineate the genetic underpinnings of CHD through genome-wide analytic techniques and high-throughput sequencing. These new programs will interact with the Pediatric Heart Network and its existing clinical trials/research infrastructure, to rapidly translate any promising findings to the clinical world.

	Expedited Publication

Top State-of-the-Art Paper Clinical Research Pre-Clinical Research News from the NHLBI Expedited Publication

 
Expedited Publication.   Rosuvastatin Effective in JUPITER Trial Patients With CKD

1266

Paul M. Ridker, Jean MacFadyen, Michael Cressman, Robert J. Glynn

Individuals with moderate chronic kidney disease (CKD) are at an increased risk of myocardial infarction, stroke, and vascular death, yet the efficacy of primary prevention with statins is controversial in this population. Ridker and colleagues performed a subset analysis of the JUPITER (Justification for the Use of statins in Prevention–an Intervention Trial Evaluating Rosuvastatin), dividing subjects by the presence or absence of moderate CKD, defined as an estimated glomerular filtration rate <60 ml/min/1.73 m². The JUPITER participants with CKD had higher vascular event rates (hazard ratio: 1.54) and a 45% reduction in risk of myocardial infarction, stroke, hospitalization for unstable angina, arterial revascularization, or confirmed cardiovascular death, and a 44% reduction in all-cause mortality when randomized to rosuvastatin. Because of the higher event rates in those with moderate CKD, the number needed to treat at 5 years was 14 for the primary end point, and 9 for the end point that also included total deaths and venous thromboembolism, compared to 35 and 25, respectively, for those with more preserved renal function.

Related Articles

Screening for Cardiovascular Risk in Asymptomatic Patients

Jeffrey S. Berger, Courtney O. Jordan, Donald Lloyd-Jones, and Roger S. Blumenthal
J. Am. Coll. Cardiol. 2010 55: 1169-1177. [Abstract] [Full Text] [PDF]

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