Drug-eluting stents for erectile dysfunction

by Shelley Wood

Technorati Tags: DES,Stents,Mandul,Erectile dysfunction,Disfungsi Ereksi

San Francisco, CA - Nine hospitals in the US are embarking on a stent trial that will no doubt perk the attention of interventionalists and patients alike. Amid all of the larger coronary stent trials making waves at TCT 2009 last week, Dr Jason H Rogers (UC Davis Medical Center, Sacramento, CA) got up and announced the launch of the ZEN trial, testing the use of a zotarolimus-eluting stent for the treatment of erectile dysfunction.

The trial, sponsored by Medtronic, is enrolling 50 men who've failed treatment with phosphodiesterase-5 (PDE-5) inhibitors and have angiographic evidence of internal pudendal artery disease amenable to percutaneous treatment.

Speaking with heartwire after TCT, Rogers reviewed the rationale for the trial. In four out of every five men with erectile dysfunction, he notes, the etiology is vasculogenic, and erectile dysfunction itself shares a host of risk factors with coronary artery disease, including age, diabetes, hypertension, dyslipidemia, and smoking.

"Up to 70% of men with coronary disease also have erectile dysfunction," Rogers said. "The development of erectile dysfunction predates the onset of symptomatic atherosclerotic disease by approximately 36 months, [yet] erectile dysfunction is not routinely screened by vascular specialists."

Correlation between vascular beds

Rogers and colleagues have already completed a pilot study, called the Pelvic Angiography in Non-Responders to PDE-5 Inhibitors (PANPI), which correlated angiographic evidence of coronary disease with pudendal arterial disease. In PANPI, 10 patients undergoing coronary angiography for CAD symptoms who also reported a poor response to PDE-5 inhibitors underwent a pelvic angiogram as well. Results showed that stenosis in the coronary arteries typically mirrored that of the pudendal artery, which ranged from a mean of 52% in the right internal pudendal artery to 60% in the left.

"We basically found a 100% correlation" between coronary artery disease and pudendal artery disease, Rogers told heartwire, "The pattern of disease is similar to that of the coronary arteries, and it appeared that it would be amenable to a stent."

Surprisingly—or not—men enrolled in PANPI were not overly interested in their coronary angiograms. "Despite the fact that we were diagnosing significant stenosis in the [left anterior descending] LAD, circumflex, and right coronary arteries, what they cared about was what the pudendal angiograms were showing," Rogers said.

Rogers noted that, to the best of his knowledge, there are no other studies looking at drug-eluting stents in the pudendal artery, although there were some early angioplasty studies that typically failed to demonstrate a long-term benefit due to problems of restenosis. Rogers would not reveal what stent is being used in ZEN, saying only that Medtronic was "leveraging technology in its inventory" and that this device was zotarolimus-eluting.

He also clarified: "This isn't stenting the penis," but rather the pudendal artery, which is located in the pelvis.

The ZEN trial represents a new opportunity for collaboration between urologists and cardiologists, Roger added—disciplines that have not interacted closely in the past. "A key message for cardiologists is that our practice is actually rich in patients with erectile dysfunction, and we don't do as good a job as we should at identifying people with erectile dysfunction," he told heartwire. "It's been shown that erectile dysfunction is a risk factor for CAD or CVD, and potentially, there may even be a therapy for this that cardiologists could deliver."

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Left Main Artery Restenosis After Stent Placement Often Amenable to PCI

by Will Boggs, MD

Technorati Tags: coronary heart disease,invasive cardiology,Stent,DES,chest pain,PCI

NEW YORK (Reuters Health) Oct 06 - In most patients who receive drug-eluting stents for unprotected left main disease, restenosis can be managed with a minimally invasive approach, including placement of additional drug-eluting stents, according to results from the Failure in Left Main Study (FAILS).

"The FAILS study shows that repeat percutaneous coronary intervention (PCI) can be safely and effectively performed in most cases of left main restenosis," Dr. Giuseppe Biondi-Zoccai from the University of Turin, Italy told Reuters Health. "Yet, in a small but still relevant subset of patients, coronary artery bypass grafting (CABG) will still be needed, especially when restenosis is diffuse or atherosclerotic disease elsewhere in the coronary vessels is progressing rapidly."

Dr. Biondi-Zoccai and colleagues analyzed the incidence and management of restenosis in a cohort of 718 patients with unprotected left main disease who were managed with drug-eluting stents. Restenosis developed in 70 patients (9.7%).

Overall, 22.1% of cases were diagnosed during routine follow-up angiography, and 30.8% were found in patients who had been admitted for acute coronary syndrome.

According to the report in the September 22nd Journal of the American College of Cardiology, 59 of the 70 patients (84.3%) were treated again with PCI. In the repeat-PCI group, 34 patients had a new drug-eluting stent implanted, 1 received a bare metal stent, and 16 had balloon-only PCI. Six were treated with cutting balloons, and 2 underwent directional atherectomy.

Another 7 patients (10%) were managed with CABG, and 4 (5.7%) were treated with medical therapy only.

There was one in-hospital death in the repeat PCI group and none in the medical therapy or CABG groups.

Over an average of 25.6 months after restenosis, the major adverse coronary event rate was 25.7%, with death in 5.7%, myocardial infarction in 2.9%, target lesion revascularization in 21.4%, and PCI on other vessels in 21.4%. In the PCI group, there was 1 case of possible stent thrombosis, 1 case of probable stent thrombosis, and no cases of definite stent thrombosis, the investigators say.

"The bottom line of the FAILS study is that left main restenosis after PCI is not by default an indication to CABG," Dr. Biondi-Zoccai told Reuters Health. "If, in a given patient, the same reasons leading to the choice of PCI vs. CABG still hold true, than repeat PCI is feasible, safe, and can effectively manage symptoms and signs of ischemia in most subjects."

"However," Dr. Biondi-Zoccai added, "if coronary disease is extensive, restenosis is diffuse, uncontrolled diabetes mellitus is present, surgical risk is not prohibitive, and/or the patient wishes to minimize the risk of repeat revascularization, then CABG should be viewed as the treatment of choice instead of PCI for unprotected left main restenosis."

Reference

J Am Coll Cardiol 2009;54:1131-1136.

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Revascularization can boost diastolic function, too

by Steve Stiles

Perugia, Italy - Yes, diastolic function can improve after revascularization in the setting of ischemic LV systolic dysfunction, notes a small study that isn't revelatory but confirms and quantifies a phenomenon that has long seemed likely without having been clearly demonstrated, according to researchers [1].

They saw significant improvement in LV diastolic filling on tissue-Doppler imaging (TDI) and in LVEF on conventional echocardiography in 26 patients who underwent PCI or CABG of coronaries serving hibernating, hypo-, or akinetic myocardium, which was demonstrated by dobutamine-echo viability imaging.

"These results support the tenet that in ischemic heart disease, systolic and diastolic function go hand-in-glove and directly demonstrate that revascularizing chronically viable, dyssynergic myocardium may also beneficially impact diastolic function," write the authors, led by Dr Erberto Carluccio (Ospedale Silvestrini, Perugia, Italy) in the June 2009 issue of the European Heart Journal.

The work lends "further support to the concept that a thorough search for viability (and, hence, for possible revascularization) should be part of the diagnostic workup of patients with ischemic cardiomyopathy."

In clinical practice, the overwhelming focus of revascularization in this setting has been on improvement in systolic function, observed primary author Dr Giuseppe Ambrosio (Ospedale Silvestrini) for heartwire. It has followed intuitively that deficits in diastolic function might also improve, but "sometimes, things that seem obvious are not put to the test," he said. So he and his group used pulsed-wave Doppler and TDI techniques available only in recent years to quantify changes in parameters that reflect diastolic function in revascularized hibernating myocardium.

Seven patients undergoing PCI and 24 undergoing CABG, all with chronic ischemic cardiomyopathy, a mean LVEF of 32%, a mean regional wall-motion score of 2.45 (2=hypokinesia; 3=akinesia), and viable myocardium in abnormally contracting regions (as measured by low-dose dobutamine echocardiography) were evaluated at baseline and after at least four months (mean, eight months).

At baseline, 10 and 16 patients, respectively, showed restrictive and nonrestrictive diastolic filling patterns at transmitral pulsed-wave Doppler imaging; after revascularization, only three patients still showed a restrictive filling pattern (p=0.016), according to the authors. The improvement appeared unrelated to changes in systolic function.

On TDI, overall early diastolic annular velocity (E') had improved by 32% (p=0.0028) and the ratio of global peak early diastolic flow velocity to E' (E/E'), a gauge of filling pressure, had fallen by 19% (p=0.0378)

Also improving were mean LVEF (from 32% to 43%; p=0.0004), end-diastolic volume index (124 mL/m² to 106 mL/m²; p=0.0024), and end-systolic volume index (85 mL/m² to 63 mL/m²; p=0.0004)

Mean NYHA functional class improved from 2.9 to 1.7 (p=0.0002); the gains correlated significantly with the degree of contractile-function improvement and the number of myocardial segments showing functional recovery after revascularization. They were also significantly related to improvement in E/E' (p=0.0328), but not to improvement in E'.

The message of the study, said Ambrosio, is simple, but in practice it isn't frequently considered: viability studies should be performed in patients with ischemic cardiomyopathy and ventricular dysfunction, and when viability is seen in poorly functioning segments served by a diseased coronary, revascularization can potentially improve both systolic and diastolic performance.

Source

1. Carluccio E, Biagioli P, Alunni G, et al. Effect of revascularizing viable myocardium on left ventricular diastolic function in patients with ischaemic cardiomyopathy. Eur Heart J 2009; 30:1501-1509.

Technorati Tags: ischaemic cardiomyopathy,catheterization,coronary heart disease,CABG

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Hypersensitivity likely the culprit in late stent thrombosis

by Lisa Nainggolan

Bern, Switzerland - A small Swiss study has shown that late hypersensitivity reactions likely play a major role in the pathogenesis of very late stent thrombosis in patients with drug-eluting stents (DES) [1]. Dr Stéphane Cook (University Hospital, Bern, Switzerland) and colleagues report their findings online July 20, 2009 in Circulation.

Senior author Dr Stephan Windecker (University Hospital) told heartwire: "This is a small paper explaining from a pathophysiologic standpoint a very rare clinical problem. People should not be worried, because it's a very rare adverse event and first-generation DES have been shown to be safe overall—the incidence of death or MI as compared with bare-metal stents is not increased—so there is no concern about this."

In an accompanying editorial [2], Dr William Wijns (Cardiovascular Center Aalst, Belgium) says that Cook et al "now confirm that local hypersensitivity reactions are the more likely mechanisms of very late stent thrombosis through excessive positive remodeling." Wijns told heartwire, "In retrospect, this new study explains a lot of controversies we didn't understand." Thus, the seemingly erratic pattern of very late stent thrombosis, the steady linear increase over time with no evidence of decreased event density with extended follow-up, and the weak association with discontinued dual antiplatelet therapy (in contrast to early thrombotic events) "are all consistent with the evoked mechanism of action," he says.

The work also raises a number of new questions and has implications for future research, says Wijns.

An unusual reaction explaining many mysteries

The new study looked at just 28 patients with very late stent thrombosis and 26 controls. Of the 28 patients with late stent thrombosis, 10 patients underwent both thrombus aspiration and intravascular ultrasound (IVUS). Incomplete stent apposition (ISA), also known as malapposition, and evidence of vessel remodeling were present in 73% of cases. Histopathological analysis showed much higher numbers of eosinophils in the specimens from very late DES thrombosis compared with other causes of MI—particularly with sirolimus-eluting stents—and a correlation with the extent of stent malapposition.

Windecker said: "This is an extension of work we have previously published showing an exceedingly high incidence of stent apposition in those presenting with very late stent thrombosis. What we did in this new study was correlate those findings with histopathological analysis of thrombus aspirates from living patients, and we found that the extent of vessel remodeling as diagnosed by IVUS correlated directly with the amount of eosinophilic infiltrates." An increase in eosinophils is "very unusual" he noted, and "implies a hypersensitivity reaction."

Wijns says that what Cooke et al found "in all those cases was that there was necrotizing vasculitis around the stent struts and that explains why the wall is moving away from the stent, this phenotype of malapposition." However, malapposition itself is "a moving target" he explained, "as early IVUS studies have shown it can be there from the onset and disappear, it can be present from the onset and stay as it is, or it can also be absent initially and then appear—perhaps the latter instances are the ones that are potentially related to this delayed inflammatory reaction," he observes. But whether malapposition per se is sufficient to trigger thrombosis "is unclear," he says.

Also, this study "cannot tell us exactly which component of the drug-polymer device is responsible for the late hypersensitivity reaction because, by definition, late hypersensitivity reactions can present themselves even ages after the causal agent has gone. So it's not excluded that it could be the drug [on the DES], but I think most people agree that the polymer is likely the guilty one," Wijns added.

Windecker says: "People always wondered why it is that very late stent thrombosis occurs at a steady rate, why the stents don't heal, and why the risk doesn't seem to stop after a certain period in time. Now, with these hypersensitivity reactions, we may have a partial explanation, because hypersensitivity reactions can occur at any time."

No change in advice for those affected by stent thrombosis

Wijns says there are few practical consequences of the new findings. Removal of the DES is not possible, says Windecker, so the only course of action is medical treatment, a rescue primary PCI to open the occluded stent, give appropriate antiplatelet therapy, "and hope the stent stays open," he says. "There's really not much more that you can do."

Desensitization is not an option either, Windecker explains, because "this [hypersensitivity] reaction is not IgG-mediated, which you could suppress, rather it is T-cell or eosinophil-mediated, so the only thing you could perhaps consider is local administration of steroids, but you would have to be very careful to weigh the risks of this against the benefits of therapy."

Future directions

Wijns says this work indicates that researchers looking for the optimal drug-polymer device may be wise in the future to narrow their search for constituents down to polymers and drugs that have been used extensively in humans for other indications, with known outcomes.

It is also essential that pooling of data, following the same protocol, is performed going forward in patients presenting with stent thrombosis. This is especially important in Europe, where many new DES are available, he says. Central analysis of removed thrombus, invasive imaging by IVUS or optical coherence tomography, and efforts to help identify systemic biomarkers that could predict events, or at least those patients most at risk, "should be encouraged," he notes.

"Although stent thrombosis is rare, malapposition is not an infrequent finding, seen in 8% to 13% of patients nine to 12 months after implantation of first-generation DES. Linking this phenotype to biomarker changes may help to identify patients most at risk of late stent thrombosis, perhaps the patient subset that will benefit from long-term dual antiplatelet therapy," he observes.

"Only when we have such a biomarker will we know the fraction of patients at risk of this very rare side effect, and from there the fraction who will have the event is even lower by several orders of magnitude," he commented to heartwire. "This is no reason to panic, rather the opposite," he states, "because at last we understand what the mechanism is."

Sources

1. Cook S, Ladich E, Nakazawa G, et al. Correlation of intravascular ultrasound findings with Histopathological analysis of thrombus aspirates in patients with very late drug-eluting stent thrombosis. Circulation 2009; 120: 391-399.
2. Wijns W. Late stent thrombosis after drug-eluting stent. Seeing is understanding. Circulation 2009; 120: 364-365.

Technorati Tags: stent thrombosis,drug-eluting stent,DES,catheterization,coronary heart disease,thrombus

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PCI No Better Than Optimal Medical Therapy in Persistent Total Occlusions Three to 28 Days Post-MI: OAT and TOSCA-2

by Shelley Wood

November 15, 2006 (Chicago, IL) - Defying "logic" and "intuition," performing late angioplasty on a persistent total occlusion three to 28 days after MI does not reduce rates of death, reinfarction, or heart failure compared with optimal medical therapy, results from the Occluded Artery Trial (OAT) show. Worryingly, OAT patients treated with PCI showed a trend toward more repeat MIs than patients treated medically.

Supporters of the trial believe the findings should serve as a slap in the face to clinicians who prematurely decided, long before the results were in, that PCI would be superior, and particularly to centers that declined to randomize patients in the OAT trial on the assumption that medical management would be unethical. Indeed, OAT, which was primarily funded by the National Heart, Lung, and Blood Institute, was plagued with slow enrollment in part due to a lack of equipoise among cardiologists who believed opening the artery to be the only logical treatment.

Presenting the four-year cumulative results here at the American Heart Association 2006 Scientific Sessions, Dr Judith S Hochman (New York University, NY) stressed that in stable MI survivors who do not receive PCI within the first 12 hours, late recanalization of an occluded, infarct-related vessel does not improve on best medical therapy.

"These results support routine use of aggressive secondary prevention without revascularization as the preferred strategy," she said.

Dr Robert Califf (Duke University, Durham, NC), who discussed the OAT results, called the message "straightforward."

"There is no compelling reason to intervene on asymptomatic patients more than 24 hours after infarction with total occlusion of the infarct artery," Califf said.

Also unveiled during the late-breaking clinical-trial sessions today, the Total Occlusion Study of Canada-2 (TOSCA-2), an OAT substudy looking at the effects of PCI on late artery patency and left ventricular (LV) function, served only to complicate results repeatedly described as unintuitive. As primary investigator Dr Vladimir Dzavik (University Health Network, Toronto, ON) reported, PCI patients were more likely to have patent arteries at one year and also appeared to have less LV enlargement, despite no apparent benefit in clinical outcomes in the overall OAT trial.

"If the remodeling results of TOSCA-2 can be extrapolated to the entire OAT population, we have mild benefit, in terms of reduced LV enlargement, at the same time that we have a trend toward increased MIs that are higher in the angioplasty group, so it's likely there are competing effects," he suggested.

Both the OAT and TOSCA-2 study results were simultaneously published online today in the New England Journal of Medicine and Circulation, respectively [ 1 , 2 ].

OAT results

In OAT, 2166 stable patients with total occlusions of their infarct-related arteries were randomized to either routine PCI plus stenting and optimal medical therapy (n=1082) or optimal medical therapy alone (n=1082), three to 28 days after their MI. Patients with significant left main or three-vessel disease, angina at rest, hemodynamic or electrical instability, NYHA class 3 or 4 heart failure, or shock were excluded from the trial.

At follow-up, the estimated four-year cumulative primary event rate--a composite of death, reinfarction, or heart failure--did not differ between the PCI group and the medical group, a finding that held up in intention-to-treat analyses. Individually, rates of death and rates of heart failure were also no different between the two groups; however, the rate of nonfatal reinfarction trended to be higher among PCI-treated patients. Indeed, in secondary-end-point analyses based on site-determined event rates (that Hochman described as a more accurate reflection of international definitions of MI), the difference in nonfatal reinfarction rates between the two groups reached statistical significance (p=0.04).

Of note, a nuclear imaging ancillary study of myocardial viability in a subset of 124 patients indicated that 69% of patients had moderate retained viability in the infarct zone.

Four-year cumulative event rates in OAT

Outcome	PCI (%)	Medical (%)	Hazard ratio	95% CI	p
Death, MI, HF	17.2	15.6	1.16	0.92–1.45	0.20
All MI	7.0	5.3	1.36	0.92–2.00	0.13
Nonfatal MI	6.9	5.0	1.44	0.96–2.16	0.08
NYHA class 4 HF	4.4	4.5	0.98	0.64–1.49	0.92
Death	9.1	9.4	1.03	0.77–1.40	0.83

Fewer patients had angina among the PCI-treated patients at four months and one year, but over time the occurrence of angina declined in the overall study population, and the differences between the two groups disappeared.

As such, PCI is a reasonable strategy to treat persistent angina but not to prevent angina, Hochman clarified. "So if you have a patient who meets the eligibility criteria for OAT and you're not intervening as a routine strategy to make them live longer or prevent MI or HF, and they develop angina that's either severe or affects lifestyle, PCI is an effective therapy."

Referring to the "modest reduction" in angina, Califf called this finding "difficult to place in context" and concluded that it had no impact on the overall results of the study.

TOSCA 2: Artery patency and LV effects at odds with clinical outcomes in OAT

A total of 381 patients enrolled in the OAT study were included in the TOSCA-2 ancillary study, in which coronary and LV angiography was performed one year after randomization. Earlier studies have suggested that PCI beyond the accepted period of myocardial salvage might lead to improved left ventricular function and slow LV remodeling.

TOSCA-2 results indicated that 83% of PCI-treated patients had patent infarct-related arteries at one year, compared with 25% in the medical therapy group (p<0.001). LV ejection fraction improved in both groups by roughly 4%, but with no significant differences between the two groups. Change in LV end-diastolic volume index was lower in the PCI group, at 3.2 mL/m², vs 5.3 mL/m² in the medical-therapy-only group, suggesting that PCI had a favorable effect in terms of reducing ventricular enlargement. This finding only trended toward statistical significance, however, and Dr Eric R Bates (University of Michigan, Ann Arbor), the discussant for the TOSCA-2 trial, emphasized that this observation, while intriguing, was drawn from a subset of a subset, since only 42% of the TOSCA-2 cohort underwent volume determination studies.

In an interview with heartwire , Dzavik acknowledged that one-year follow-up in the TOSCA-2 substudy may not have been enough. "The real question is, will that tendency for the PCI to reduce expansion of the heart override the MI results over long-term follow-up? Or will the tendency of the procedure to cause more infarcts be the overriding factor?"

Califf agreed: "It would be great to have more follow-up--the intriguing small difference in end-diastolic volume: could that enable the PCI group to look better over time, or could the more impressive excess MI rate in the PCI group, if that continues, [provide] more persuasive evidence not only of failure to benefit but actual harm of invasive, aggressive treatment?" Out to three years, he added, the event curves for reinfarctions show no signs of coming together.

What about patients excluded from OAT?

Also unanswered by OAT are questions about higher-risk and unstable-MI patients who were excluded from the OAT and TOSCA-2 studies.

"The criticism will be, well, you didn't enroll high-enough-risk patients," Dzavik acknowledged, noting that this will be sufficient for some operators to justify continuing to use angioplasty outside the recommended therapeutic window. But the fact remains, he noted, that the types of patients currently being referred for PCI outside the guideline-recommended 12-hour period are precisely the types of patients included in OAT. "It is in this large group of patients where there should be an impact [of OAT and TOSCA-2]. There should be a reduction in procedures, which are probably unnecessary in this group."

Indeed, during a media briefing, Hochman estimated that approximately 100 000 MI patients per year in the US would meet the OAT criteria. However, both Hochman and Dzavik stressed repeatedly to the press that the OAT findings do not apply to higher-risk patients.

"Nobody has any doubt that high-risk patients need to have their arteries opened," Dzavik told heartwire . But in the two groups of patients who might be expected to benefit--patients with infarcts in left anterior descending (LAD) arteries and patients with lower ejection fractions--"we found no differences in clinical outcomes in these patients," he said.

Most experts commenting on the study expressed the hope that physicians, armed with these new results, would put aside their previous biases.

Dr Paul Armstrong (University of Alberta, Edmonton) described OAT and TOSCA-2 as a lesson in what not to do. "We've learned some important lessons, and they should help us in reallocating resources, when even in the great US cost containment has become an important issue," he said.

Bates, discussing the TOSCA-2 findings, emphasized that despite earlier studies suggesting a benefit of improved LV function following PCI, these have not translated into better clinical outcomes: "It should be very clear that there is no role for routine delayed PCI in improving LVEF in stable patients with an occluded infarct artery after MI. This [information] probably should immediately be transferred into clinical practice. I have no doubt that it will be embraced by the guidelines committee, and I bet the appropriateness boys will use this when they evaluate our future performance of PCI."

To heartwire , Dr Kim Fox (London, UK) hinted that old habits die hard, and he expressed his "sincere hope" that clinicians will change their minds about using PCI in stable patients three days post-MI. "They may not--there is a great wish and desire to do angioplasty on an occluded vessel simply because you see it's occluded: it's easy to do, and the results are good. But I certainly hope this causes people to think about this problem."

Califf had even stronger words, particularly for American cardiologists and investigators, who he suggested had unwittingly compromised the generalizability of the OAT results to the US population by doing such a lousy job of enrolling patients.

"Let me browbeat my colleagues in the US," Califf said. Over five years, he noted, US sites enrolled only 489 patients. "If anything, this trial points out that we are in serious trouble in the conduct of clinical trials in the US."

Worse still, some of the "nation's best centers" refused to participate because they believed they already knew the answers, Califf said. "Unfortunately they had it backward, and I would raise the question: Is this an issue of knowing an answer to the scientific question, or was it a case of putting the pocketbook, the ability to reap financial rewards from doing the procedures, over the interests of patients being given the opportunity to participate in a clinical trial that would answer a very important question?" Califf asked.

Ultimately, Califf chided, OAT was a study funded by US taxpayers, yet the majority of patients were randomized outside the US.

1. Hochman JS, Lamas GA, Buller CE, et al. Coronary intervention for persistent occlusion after myocardial infarction. N Engl J Med 2006; DOI: 10.1056/NEJM0a066139. Available at: http://www.nejm.org .
2. Dzavik V, Buller CE, Lamas GA, et al. Randomized trial of percutaneous coronary intervention for subacute infarct0related coronary artery occlusion to achieve long-term patency and improve ventricular function. The Total Occlusion Study of Canada (TOSCA)-2 trial. Circulation 2006; DOI: 10.1161/CIRCULATIONAHA.106.669432. Available at: http://circ.ahajournals.org .

Technorati Tags: PCI,MI,myocardial infarction,percutaneous coronary intervention,Chest pain,AMI,Coronary Artery

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