INSIDE THIS ISSUE OF JACC
Inside This Issue of JACC
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Clinical Trial
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Oral MMP Inhibitor Fails to Protect Against LV Remodeling.
Matrix metallproteinases (MMPs) are proteolytic enzymes that degrade the extracellular membrance (ECM) that provides the scaffolding for cardiac myocytes. Enhanced activity of these enzymes has been associated with left ventricular (LV) remodeling and progressive heart failure. PG-116800 is an oral MMP inhibitor developed for use in patients with arthritis. The PREMIER (Prevention of Myocardial Infarction Early Remodeling) trial randomized patients within 48 h of an ST-segment elevation myocardial infarction to either PG-116800 or placebo. There was no difference in the primary end point of LV end-diastolic volume 90 days later. Other efficacy end points also suggested no benefit to MMP inhibition. Whereas inhibiting breakdown of the ECM appears to be beneficial in animal models, there is no evidence of clinical utility for this drug in preventing LV remodeling in humans. See page 15.
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Interventional Cardiology
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Mandatory Angiographic Follow-Up Increases TVR by 40%.
The fact that most trials comparing drug-eluting stents (DES) with bare-metal stents (BMS) required angiographic follow-up at 9 months has raised concern that the clinical benefit of DES may be overestimated as a result of the "oculostenotic reflex." Pinto and colleagues used data from the TAXUS-IV trial, which randomized patients to either a paclitaxel-eluting stents (PES) or BMS. In this trial, the first 500 patients had protocol-mandated angiographic follow-up at 9 months, whereas the other subjects were followed for clinical events only. Those assigned to angiographic follow-up were nearly 40% more likely to undergo target vessel revascularization (TVR) than those assigned to clinical follow-up. The increases were similar for both BMS and PES groups such that PES reduced TVR by  60% regardless of follow-up. The authors conclude that future studies designed to determine the true clinical benefits of DES should either forgo routine angiographic follow-up or separate the time of repeat angiography from the primary clinical end point by as long as possible. See page 32.
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Coronary Artery Disease
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Understanding the Hemodynamics of Collateral Circulation.
Two articles and an editorial in this issue use coronary pressure wires to measure the complex hemodynamics involved in collateral recruitment and de-recruitment. In the first paper by Werner and colleagues, adenosine infusion produced coronary steal in about one-half of patients with chronic total occlusions (CTOs). Those who demonstrated steal had either an atherosclerotic lesion in the donor artery or reduced vasodilatory capacity in the microcirculation. Zimarino and colleagues studied the timing of "de-recruitment" of collateral circuits after the opening of CTOs. They measured flow through collateral arteries before and after opening a CTO; they then stimulated restenosis 10 and 20 min later with balloon inflations and assessed chest pain and ST-segment changes. Flow through the coronaries was found to be substantially reduced after only 10 min, and further reduced over time, suggesting that these patients will be more susceptible to angina should the vessel reocclude. An editorial by Morton Kern places these findings in historical perspective. See pages 51, 59, and 66. See figure.
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Heart Rhythm Disorders
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T-Wave Alternans Screening Improves Cost Effectiveness for ICDs.
Implantable cardioverter-defibrillators (ICDs) have been shown to prevent mortality in patients with ischemic cardiomyopathy; some estimates have suggested that implanting an ICD in every eligible patient would cost more than $2.5 billion/year. Microvolt T-wave alternans (MTWA) testing may be useful in stratifying the subsequent risk of sudden cardiac death, with some studies suggesting that the risk of sudden cardiac death is >2 times higher in those with non-negative MTWA. Chan and colleagues created a Markov model that allows the comparison of several variables regarding efficacy and cost to determine the optimal strategy for identifying who should receive an ICD. In this model, providing ICDs only to those whose MTWA was non-negative resulted in an incremental cost-effectiveness ratio (ICER) of $48,700/quality-adjusted life-year over medical therapy. Placing ICDs in all patients would result in an ICER of $88,700/quality-adjusted life-year, compared to MTWA testing first. This study suggests that risk stratification with MTWA testing in MADIT-II eligible patients improves the cost-effectiveness of ICDs. See page 112. See figure.
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Cardiac Imaging
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Delayed Enhancement MSCT Accurately Measures Infarct Size.
Delayed enhancement magnetic resonance imaging (DE-MRI) is now the gold standard for measuring infarct size in living animals. This technique relies on the fact that gadolinium contrast can accumulate in areas of increased extracellular fluid; iodinated contrast behaves in a similar fashion, but the imaging quality of computed tomography has lacked the spatial and temporal resolution until the recent deployment of multi-slice computed tomography (MSCT). Researchers at the Thoraxcenter created controlled infarctions in 14 pigs; approximately 5 days later, they sequentially performed DE-MRI and DE-MSCT. The hearts were then excised and stained with triphenyltetrazolium chloride for pathologic staining. There was excellent correlation among all 3 techniques. This study suggests that DE-MSCT may be as accurate as DE-MRI for infarct sizing/detection, although the optimal timeframe and protocol for DE-MSCT requires further study. See page 144. See figure.
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Cardiac Imaging
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Adenosine Infusion Allows Assessment of Perfusion with MDCT.
Multi-detector computed tomography (MDCT) has been shown to accurately classify coronary lesions as > or < 50%, but lacks the ability to assess myocardial perfusion in territories distal to these segments or the severity of obstruction in heavily calcified segments. George and colleagues measured the signal intensity of myocardial contrast in segments before and after the infusion of adenosine in a canine model of coronary stenosis and compared these measurements with microsphere infusions. There was a significant and linear relationship between myocardial blood flow and tissue signal density. This study suggests that adding an assessment of myocardial blood flow during hyperemia may allow for physiologic assessment of coronary stenoses. See page 153. See figure.
Related Article
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Effects of Selective Matrix Metalloproteinase Inhibitor (PG-116800) to Prevent Ventricular Remodeling After Myocardial Infarction: Results of the PREMIER (Prevention of Myocardial Infarction Early Remodeling) Trial
- Michael P. Hudson, Paul W. Armstrong, Witold Ruzyllo, Jose Brum, Lisa Cusmano, Piotr Krzeski, Robert Lyon, Miguel Quinones, Pierre Theroux, Diana Sydlowski, Henry E. Kim, Mario J. Garcia, Wael A. Jaber, and W. Douglas Weaver
J. Am. Coll. Cardiol. 2006 48: 15-20.
[Abstract]
[Full Text]
[PDF]
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Clinical Trial
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