Coronary intervention for persistent occlusion after myocardial infarction

This article [1] and associated editorial [2] reports on the results of the Occluded Artery Trial (OAT), which examined whether or not a strategy of routine PCI for total occlusion of the infarct-related artery 3–28 days after acute myocardial infarction (MI) would reduce the occurrence of a composite end point of death, reinfarction, or New York Heart Association (NYHA) class IV heart failure.

The OAT study was a 4-year randomized study with a total of 2166 patients who met eligibility for enrollment if they had a total occlusion of the infarct-related artery 3-28 days after MI and met a high-risk criterion (an ejection fraction of <50% or proximal occlusion). A total of 1082 patients were assigned to routine PCI and stenting with optimal medical therapy and 1084 were assigned to optimal medical therapy alone. The primary end point was a composite of death from any cause, reinfarction, or NYHA class IV heart failure with hospitalization or admission for a stay in a short-stay unit. Secondary end points included the separate component of the primary end points in addition to symptoms and other clinical events. An additional end point was recurrent elevation of a cardiac marker within 48 hours after randomization as confirmed by the sites.

The cumulative primary event rate was 17.2% in the PCI group and 15.6% in the medical therapy group (hazard ratio for death, reinfarction, or heart failure in the PCI groups as compared with the medical therapy group, 1.15; 95% confidence interval [CI], 0.92 to 1.45; P=0.20). Rates of myocardial reinfarction (fatal and nonfatal) were 7.0% and 5.3% respectively (hazard ratio, 1.36; 95% CI, 0.92 to 2.00; P=0.13). Rates of nonfatal reinfarction were 6.9% and 5.0% respectively (hazard ratio, 1.44; 95% CI, 0.96 to 2.16; P=0.08); only six reinfarctions (0.6%) were related to assigned PCI procedures. Rates of NYHA class IV heart failure (4.4% vs 4.5%) and death (9.1% vs 9.4%) were similar. No interaction between treatment effect and any subgroup variable was found.

The authors concluded that PCI did not reduce the occurrence of death, reinfarction, or heart failure although there was a trend toward an excess risk of reinfarction in the PCI group that was greatest during the first 30 days after PCI, but persisted throughout the 5-year follow-up.

1. Hochman JS, Lamas GA, Buller CE, et al. Coronary intervention for persistent occlusion after myocardial infarction. N Engl J Med 2006;355:2395-2407 

2. Hillis LD, Lange RA. Myocardial infarction and the open-artery hypothesis (Editorial). N Engl J Med 2006;355:2475-2476

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See also: Randomized trial of percutaneous coronary intervention for subacute infarct-related coronary artery occlusion to achieve long-term patency and improve ventricular function

Six-month outcome of emergency percutaneous coronary intervention in resuscitated patients after cardiac arrest complicating ST-elevation myocardial infarction 

Six-month outcome of emergency percutaneous coronary intervention in resuscitated patients after cardiac arrest complicating ST-elevation myocardial infarction

This study [1] examines the benefit of successful reopening of the infarct-related artery in patients with acute myocardial infarction (AMI) who have had resuscitated cardiac arrest by reviewing data from consecutive patients undergoing emergency percutaneous coronary intervention (PCI) after cardiac resuscitation.

Data were collected on consecutive patients meeting the study criteria from 1995 to 2005 in five centers in France with high volumes of PCI. A total of 186 patients were identified who were resuscitated from cardiac arrest complicating acute ST-elevation myocardial infarction and were referred to the cardiac catherization lab to undergo immediate PCI. Of these patients, 78% were men and the mean age was 60.4±13.8 years. These patients were followed for at least 6 months.

Mobile medical care units performed prompt pre-hospital management in 154 of the 186 patients while 32 patients had in-hospital cardiac arrest. On admission, infarct location was anterior in 105 patients and 96 patients were in shock. Of the 186 patients, PCI (stenting rate 90%) was successful in 161 patients (87%). At 6 month follow up, the survival rate was 100 of 186 (54%) and a 48% survival rate without neurological sequelae. Multivariant analysis showed that predictors of 6-month survival were: 1) shorter interval between the onset of cardiac arrest and arrival of a first responder (odds ratio, 0.67; 95% CI 0.54–0.84); 2) a shorter interval between the onset of cardiac arrest and return of spontaneous circulation (odds ratio, 0.91; 95% CI, 087–0.96); and 3) absence of diabetes (odds ratio, 7.30; 95% CI, 1.80–29.41).

The authors conclude that this study demonstrates that in the patients admitted to the hospital for resuscitated cardiac arrest complicating AMI, prompt pre-hospital medical management and early revascularization were associated with a 54% survival rate at 6 months. In addition to these variables, independent predictors of 6 month survival in these patients included the absence of shock, diabetes and prior PCI. Study limitations included: nonrandomized, observational registry; exclusion of patients who died from the study; wide confidence intervals for shock and absence of prior PCI (independent predictors of 6-month survival), which might suggest that the analysis should focus more on the univariate analysis and less on the multivariate models. The authors note that this study emphasizes that “the interval between the onset of cardiac arrest and return of spontaneous circulation, reflecting prompt arrival at the scene and adequate out-of-hospital medical care, is one of the key determinants in patient survival.” They emphasize “the role and importance of patient and family education about the warning signs of cardiovascular disease and lay person intervention such as cardiopulmonary resuscitation to ultimately improve survival in cardiac arrest.”

1. Garot P, Lefevre T, Eltchaninoff H, et. Six-month outcome of emergency percutaneous coronary intervention in resuscitated patients after cardiac arrest complicating ST-elevation myocardial infarction. Circulation 2007;115(11):1354-1362. 

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See also: Randomized trial of percutaneous coronary intervention for subacute infarct-related coronary artery occlusion to achieve long-term patency and improve ventricular function

Randomized trial of percutaneous coronary intervention for subacute infarct-related coronary artery occlusion to achieve long-term patency and improve ventricular function: The total occlusion study of Canada (TOSCA)-2 trial

The Total Occlusion Study of Canada (TOSCA)-2 trial [1] is a mechanistic ancillary study of the Occluded Artery Trial (OAT). The TOSCA-2 trial was designed to determine whether percutaneous coronary intervention with stenting in addition to optimal medical therapy in the subacute phase after myocardial infarction (MI) compared with optimal medical therapy alone yields superior, long-term IRA patency and whether this strategy improves LV function and size at 1 year.

The investigators enrolled 381 patients, who mirrored the criteria for OAT (occluded native IRA 3 to 28 days after MI; median 10 days). The patients were randomly assigned to percutaneous coronary intervention with stenting (PCI) or optimal medical therapy alone (MED). Repeat coronary and LV angiography was performed 1 year after randomization (n=332, 87%). Two co-primary end points were specified and included follow-up IRA patency and change in LV ejection fraction (LVEF); secondary end points included change in LV end-systolic volume index (LVESVI, LV end-diastolic volume index (LVEDVI) and regional wall motion score.

PCI was successful in 92%. At 1 year, 83% of the PCI versus 25% of the MED patients had a patent IRA (P<0.001); LV ejection fraction increased significantly (P<0.001) in both groups, with no between group difference: PCI 4.2±8.9 (n=150) versus MED 3.5±8.2 (n=136; P=0.47) . Median change (interquartile range) in LV end-systolic volume index was -0.5 (-9.3 to 5.0) vs 1.0(-5.7 to 7.3) ml/m² (P=0.10) in comparison to median change (interquartile range) in LV end-diastolic volume index, which was 3.2 (-8.2–13.3) vs 5.3 (-4.6–23.2) ml/m² (P=0.07 in the PCI (n=86) and MED (n=76) groups, respectively. The results of the TOSCA-2 trial found that PCI with stenting of a persistently occluded IRA in the subacute phase after MI effectively maintains long-term patency, but does not have an effect on LVEF. The authors noted that both treatment groups had significant improvement in target-region wall motion, but there was a trend toward greater improvement in the PCI group. They suggest that “heterogeneity of the responses implies that mechanisms other than vessel patency are operative.” They also reviewed the results in terms of OAT and noted that “TOSCA-2 confirms that PCI resulted in 1-year patency that exceeded 80%, yet OAT showed that PCI did not reduce the combined end point of death, recurrent MI or New York Health Association class IV congestive heart failure.”

Based on the TOSCA-2 findings, PCI for persistent IRA occlusion in stable patients days to weeks after MI is not recommended. These authors are planning a follow-up of the OAT cohort “to better define the balance between a potential long-term benefit resulting from improved LV remodeling versus the adverse effect of the trend toward excess reinfarction” found in OAT.

1. Dzavik V, Buller CE, Lamas GA et al. Randomized trial of percutaneous coronary intervention for subacute infarct-related coronary artery occlusion to achieve long-term patency and improve ventricular function: The total occlusion study of Canada (TOSCA)-2 trial. Circulation 2006 114: 2449-2457

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Five-year follow-up of the medicine, angioplasty, or surgery study (MASS II): A randomized controlled clinical trial of three therapeutic strategies for multivessel coronary artery disease

This study [1] is a randomized controlled clinical trial that compares the relative efficacy of coronary artery bypass graft (CABG) with that of percutaneous coronary intervention (PCI) or medical treatment (MT) with symptomatic multivessel cardiac artery disease with stable angina and preserved ventricular function that requires revascularization.

A total of 20,769 patients were identified who were screened at the Heart Institute of the University of Sao Paulo between May 1995 and May 2000 and had a presumptive clinical diagnosis of CAD and underwent coronary arteriography. After exclusion of those patients not meeting the study criteria for eligibility, 2077 patients (10%) who had indications for revascularization were enrolled and randomly assigned to one of the three therapeutics groups, CABG (n=203), PCI (n=205) or MT (n=203). The minimum duration of the follow up was 5 years. The primary end point was the incidence of overall mortality, Q-wave myocardial infarction, or refractory angina requiring revascularization; secondary end points included angina status and stroke or a cerebrovascular accident.

At the 5 year follow-up, primary end points occurred in 21.2% of the patients who underwent CABG; 32.7% treated with PCI and 36% receiving MT alone (P=0.0026). There was no statistically significant difference found in overall mortality among the three groups. Repeat revascularization, however, occurred in 9.4% of the MT and 11.2% of PCI groups compared with 3.9% of the CABG patients (P=0.021). Additionally, nonfatal myocardial infarction was experienced in 15.3% of the MT, 11.2% of the PCI and 8.3% of the CABG patients. The pairwise treatment of comparisons of the primary end points found no difference between the PCI and MT groups (relative risk [RR] 0.93; 95% confidence interval [CI], 0.67–1.30) although a multivariate logistic regression model and Cox analysis for proportional-hazards risk demonstrated a significant protective effort for CABG compared to MT (RR, 0.53; 95% CI, 0.36–0.77). Although none of the patients in any group had refractory angina at the end of the 5 year follow-up, patients treated with angioplasty were most likely to be free of anginal symptoms after 5 years of follow-up while there was a marked presence of anginal symptoms observed in the medical treatment only group. The authors conclude that their study “demonstrated no significant clinical relevant differences among the three therapeutic strategies in relation to cardiac-related death or total mortality” although they note that “refractory angina requiring further revascularization was higher in the PCI group compared to the CABG group and was similar to the rates for MT.” Additionally, they note that “MT patients had less relief from symptomatic angina than patients who underwent CABG or PCI.” The authors note that the ongoing Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial (comparing aggressive MT along with aggressive MT plus PCI during 3–7 years of follow-up in patients with documental myocardial ischemia) should provide further clarification about the best therapeutic approach for managing mild to moderate angina in patients with multivessel CAD.

The authors indicate that the “findings of MASS II strongly suggest that a routine strategy for PCI for patients with stable multivessel CAD is not superior to CABG surgery or MT and may be associated with lower rates of event-free survival, driven by the need for repeat revascularization.” From a clinical perspective, the authors advise that “clinicians should be restrained in their recommendations for both PCI and CABG, reserving the interventions for patients whose symptoms of angina are not well controlled on medical treatment.”

1. Hueb W. Lopes NH, Gersh BJ. Five-year follow-up of the medicine, angioplasty, or surgery study (MASS II): A randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease. Circulation 2007;115(9):1082-1089

2. King III SB. Five-year follow-up of the medicine, angioplasty, or surgery study (MASS-II): Prologue to COURAGE (Editorial). Circulation 2007;115:1064-1066

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Routine upstream initiation vs deferred selective use of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: The ACUITY Timing Trial

The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) Timing trial [1] is a large-scale (9207 patients), multicenter (450 academic and community-based institutions in 17 countries), open-label randomized trial that examines the optimal use strategy of Gp IIb/IIIa inhibitors (deferred use vs upstream administration for the prevention of composite ischemic events) in patients with moderate- and high-risk ACS undergoing an early, invasive treatment strategy. Clinical end points were assessed at 30 days. The primary 30-day endpoint was composite ischemia (death from any cause, myocardial infarction or unplanned revascularization for ischemia); major secondary end points included major bleeding (non-CABG-related) and net clinical outcomes (composite ischemia or major bleeding).

In 30 days, composite ischemia occurred in 7.9% of patients assigned to selective Gp IIb/IIIa inhibitor use compared with 7.1% of patients assigned to routine upstream Gp IIb/IIIa inhibitor administration (relative risk, 1.12; 95% confidence interval, 0.97–1.29; P=0.044 for noninferiority; P=0.13 for superiority). Thus, the criterion for noninferiority was not met. Deferred use compared with upstream use resulted in reduced 30-day rates of major bleeding (4.9% vs 6.1% respectively; P<0.001 for noninferiority; P=0.93 for superiority.) Although no significant difference in composite ischemia was found between the deferred selective use of Gp IIb/IIIa inhibitors and their upstream administration, a relative increase of up to 29% in composite ischemia with the deferred selective strategy, while not significant, did not meet the criterion for noninferiority. This finding was offset by a significant reduction in major bleeding, minor bleeding, and blood transfusion. Based on the findings, the authors concluded that both strategies appear to be clinically acceptable.

(Note: The ongoing EARLY-ACS trial will provide complementary information to this study.)

1. Stone GW, Bertrand ME, Moses JW, et al. Routine upstream initiation vs deferred selective use of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: The Acuity Timing Trial. JAMA 2007;297:591-602
2. Mahaffey KW, Harrington RA. Optimal timing for use of glycoprotein IIb/IIa inhibitors in acute coronary syndromes: Questions, answers and more questions (Editorial). JAMA 2007;297:636-639.

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A pooled analysis of data comparing Sirolimus-eluting stents with bare-metal stents

The authors of this study [1] performed a safety analysis of pooled patient-level data that was collected in 4 randomized trials (RAVEL, SIRUS, E-SIRUS, C-SIRUS) that compared sirolimus-eluting stents (878 patients) and bare-metal stents (870 patients) in a total of 1748 patients during a 4 year follow up. The primary safety end point was death from any cause; secondary safety end points included death from cardiovascular causes and noncardiovascular causes, death from any cause or Q-wave myocardial infarction, and death from any cause or any type of myocardial infarction. They also studied end points in patients with and those without diabetes.  There was no significant difference in the survival rate at 4 years in the sirolimus-stent group (93.3%), as compared with the bare-metal-stent group (94.6%), (hazard ratio for death, 1.24; 95% CI, 0.84 to 1.83; P=0.28). In the 428 patients with diabetes, however, there was a significant difference in the survival rate in the bare-metal-stent group over the sirolimus-stent group (95.6% vs 87.8%; hazard ratio for death in the sirolimus-stent group, 2.9; 95% CI, 1.38 to 6.10; P=0.0008. In this population, deaths from cardiovascular and noncardiovascular causes were more frequent in the sirolimus-stent group. Overall, rates of myocardial infarction were similar between the two groups. The rates of stent thrombosis were also similar in the two groups.

The authors note that this study is limited because 1) the analysis was underpowered; 2) the patient population was highly selected and representative of only approximately 25% of patients currently treated with drug-eluting stents; the study could not address whether prolonging dual antiplatelet therapy further (than the recommended 3 months) would reduce the risk of events; the number of fatal events; and the finding that there were more fatal events in patients with diabetes may be due to chance because the number of event was small. The authors summarize the findings as “no significant differences in the rates of death, myocardial infarction, or stent thrombosis were found.”

1. Spaulding, C, Daemen J, Boersma E et al.  A pooled analysis of data comparing Sirolimus-eluting stents with bare-metal stents.  N Eng J Med 2007;356:989-997

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See also: Safety and efficacy of Sirolimus- and Paclitaxel-eluting coronary stents

Safety and efficacy of Sirolimus- and Paclitaxel-eluting coronary stents

This study [1] sought to determine the short-term and long-term safety and efficacy of drug-eluting stents as compared with bare-metal stents. Toward this end, a pooled analysis was conducted using data from a total of nine prospective, mutlicenter, double-blind, placebo-controlled randomized trials of 1) sirolimus-eluting stents versus bare-metal stents from Cordis (RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS) and 2) paclitaxel-eluting stents versus bare-metal stents from Boston Scientific (TAXUS-1, TAXUS-II, TAXUS-IV, TAXUS-V, TAXUS-VI) . A total of 5261 patients were randomly assigned to undergo percutaneous coronary intervention (PCI) with either sirolimus-eluting or bare-metal stents (n=1748) and paclitaxel-eluting or bare-metal stents (n=3513). The following end points were examined: Stent thrombosis, revascularization of the target lesion or target vessel; any myocardial infarction and Q-wave and non-Q-wave myocardial infarction; death from any cause and from cardiac and noncardiac causes; composite death or myocardial infarction; composite death or Q-wave myocardial infarction; and composite deaths from cardiac causes or myocardial infarction.

From stent implantation through 4-year follow up, the rates of stent thrombosis did not differ significantly between the sirolimus-eluting stents as compared with the bare-metal stents (1.2% and 0.6%, respectively; P=0.20) or the paclitaxel-eluting stents, as compared with bare-metal stents (1.3% and 0.9% respectively; P=0.30). At 1 year, however, there were five episodes of stent thrombosis in patients with sirolimus-eluting stents versus none in patients with bare-metal stents (P=0.025) and nine episodes in patients with paclitaxel-eluting stents versus two in patients with the bare-metal stents (P=0.028). The 4-year rates of target-lesion revascularization were markedly reduced in both the sirolimus-stent and the paclitaxel-stent groups, as compared with the bare metal group. The cumulative 4-year rate of death from any cause did not differ significantly in the sirolimus-stent group or for the paclitaxel-eluting group from that of the bare-metal group (6.7% vs 5.3%, P=0.23 and 6.1% vs 6.6%, P=0.68 respectively).

The authors concluded that: 1) there was a small, but significant, increase in the incidence of late stent thrombosis between 1 and 4 years after implantation for drug-eluting stents even though the overall rates of stent thrombosis were not significantly increased with drug-eluting stents; 2) there was marked reductions in ischemic target-lesion revascularization and target-vessel revascularization; and 3) there were no significant differences in the cumulative rates of death or myocardial infarction at 4 years.

The authors speculate that the potential causes of late stent thrombosis might include “delayed or incomplete endothelialization, late polymer reactions, strut fractures, positive remodeling with stent malapposition with or without aneurysm formation, and new plaque rupture either adjacent to or within the statent site, among other.” They note that the study limitations include: a need for larger studies with longer-term follow up to detect small differences in event rates; the current analysis is most applicable for patients with single, previously untreated coronary lesions as reflected in the labels for sirolimus- and paclitaxel-eluting stents that were approved by the FDA; the studies used different clinical sites, adjudication committees and core laboratories with possible differences in definitions; paclitaxel-stent trials included both the commercial slow rate-release formulation and the noncommercialized moderate rate-release formulations; the protocol-specified definitions of stent thrombosis after 30 days in five of the trials required angiographic confirmation and may underestimate the true event rate; data from the sirolimus-eluting and paclitaxel-eluting stent trials was not pooled since the mechanisms underlying the safety and efficacy of these two types of stents may differ; and detailed data about the use of antiplatelet medication throughout the follow-up period were unavailable, which prevented any firm recommendations regarding the optimal duration of thienopyridine administration.

1. Stone GW, Moses JW, Ellis SG et al. Safety and efficacy of Sirolimus- and Paclitaxel-eluting coronary stents. N Eng J Med 2007;356:998-1008

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Prognostic significance of the Centers for Disease Control/American Heart Association high-sensitivity C-reactive protein cut points for cardiovascular and other outcomes in patients with stable coronary artery disease

This study [1] examines: 1) the ability of high-sensitivity C-reactive protein (hs-CRP) to predict outcomes in patients with stable coronary artery disease (CAD), a population in which there is relatively little research; 2) the independent prognostic significance of the Centers for Disease Control/American Heart Association (CDC/AHA) hs-CRP cut points in this population; and 3) whether baseline hs-CRP levels affect the magnitude of effect of the angiotensin-converting enzyme (ACE) inhibitor trandolapril on cardiovascular and other clinical outcomes. To addresses these goals, hs-CRP was measured in 3771 patients with stable CAD who were enrolled in the Prevention of Events With Angiotensin-Converting Enzyme Inhibition (PEACE) trial. The PEACE trial was a randomized, placebo-controlled trial of the ACE inhibitor trandolapril. In the PEACE trial, 8290 patients with documented stable CAD and preserved left ventricular systolic function were randomly assigned to receive trandolapril or placebo. These patients were followed up for a median of 4.8 years for cardiovascular death, myocardial infarction, or stroke, as well as new heart failure and diabetes. A blood sample was obtained at the time of enrollment in 3778 subjects and at a follow-up visit in 2777 patients (6 months to 6 years from randomization; median, 3 years).   For this study, baseline hs-CRP measurements were available in 3771 patients.  The patients were divided into 3 groups according to the CDC/AHA recommendations for hs-CRP cut points (<1, 1 to 3, >3 mg/l). For this study, 1178 (31%) patients had a baseline hs-CRP <1 mg/l; 1494 (40%) had an hs-CRP of 1 to 3 mg/l; and 1109 (29%) had an hs-CRP >3 mg/l). Patient characteristics at enrollment showed that higher baseline hs-CRP levels were significantly associated with females and traditional cardiovascular risk factors, e.g., hypertension, diabetes, smoking, hypercholesterolemia, and higher body mass index while lower baseline hs-CRP levels were seen in patients who were taking lipid-lowering therapy. Higher hs-CRP levels (>1 mg/l) were associated with a significantly greater risk of cardiovascular disease, myocardial infarction or stroke after adjustment for baseline characteristics and treatments (hs-CRP 1 to 3 mg/l: adjusted hazard ratio, 1.39; 95% CI, 1.06 to 1.81, P=0.016; hs-CRP >3 mg/l:  adjusted hazard ratio, 1.51; 95% CI, 1.15 to 2.02; P=0.003).  Elevated hs-CRP levels were also an independent predictor of new heart failure (adjusted P<0.001 for trend) and new diabetes (adjusted P<0.001 for trend). There were no significant interactions between hs-CRP levels and the effects of trandolapril on any of the outcomes discussed here.

Based on these findings, the authors concluded that “in patients with stable CAD, an elevated hs-CRP was a strong predictor of cardiovascular death, MI, or stroke, even after adjusted for baseline characteristics and treatments” and note that this effect was even evident in patients with an average hs-CRP of 1 to 3 mg/l.  Additionally, they concluded that “an elevated hs-CRP was associated with a significantly increased risk of heart failure and new diabetes.”  They note that the “magnitude of the relative benefit of ACE inhibition with trandolapril on the incidence of diabetes and heart failure was not affected by baseline hs-CRP.” They discuss possible pathophysiological reasons for the association between CRP and cardiovascular events and note that while underlying pathobiology remains under study overall epidemiological data support the association between CRP and adverse cardiovascular outcomes.  They point out that while the CDC and AHA guidelines for hs-CRP recognize the prognostic utility in using hs-CRP cut points, “the most appropriate cut points to use and the prognostic implications of CRP levels above those cut points in different populations remain incompletely defined.”  This study, however, which uses a large cohort with stable CAD, broadened the understanding about the prognostic impact of hs-CRP levels in this population.  The study shows that in this population even levels >1 mg/l are associated with increased risk for cardiovascular death, MI or stroke.  Moreover, “these data suggest that among patients with CAD, hs-CRP levels can be used to gain fundamental insight into which patients are pathobiologically unstable and at higher risk for adverse cardiovascular events.”

1. Sabatine MC, Morrow DA, Jablonski KA, et al.  Prognostic significance of the Centers for Disease Control/American Heart Association high-sensitivity C-reactive protein cut points for cardiovascular and other outcomes in patients with stable coronary artery disease.  Circulation 2007;115(12);1528-1536.

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Improved outcomes after aortic valve surgery for chronic aortic regurgitation with severe left ventricular dysfunction

This study [1] examined patients undergoing aortic valve surgery for chronic aortic regurgitation (AR) in order to compare survival among those with and without severe left ventricular dysfunction (LVD), identify risk factors for death, including LVD and date of operation, and estimate contemporary risk for cardiomyopathic patients. A total of 724 patients underwent primary isolated valve surgery for chronic AR at the Cleveland Clinic from January 1972 to January 1999. Of this total, 88 (12%) had a LV ejection fraction of 30% or less on preoperative left ventriculogram or echocardiograms. These patients constituted the severe LVD group. The other 636 (88%) patients with LV ejection fractions of greater than 30% comprised the nonsevere LVD group. Routine follow up was conducted every 2 years after surgery and cross-sectionally in 2001 to determine functional status, vital status, and whether they had undergone cardiac re-operation.  The median follow-up for survivors was 6 years (mean 8.3±6.5 years). Propensity matching was used to address the diversity of differences between the two groups in order to make a fair survival comparison.

After aortic valve surgery across the entire study time (follow up extended reliably to 25 years), survival was worse among propensity-matched patients with severe LVS as compared to otherwise similar patients with nonsevere LVD (91% vs 96% at 30 days; 81% vs 92% at 1 year; 68% vs 81% at 5 years; 46% vs 62% at 10 years; 26% vs 41% at 15 years; 12% vs 24% at 20 years; and 5% vs 12% at 25 years, (p [log rank] = 0.04); however, the survival of patients with severe LVD improved significantly across the study time frame (P=0.0004). The hospital mortality among propensity-matched patients who underwent surgery prior to 1985 was 17% in the severe LVD group (7 of 41; CL 11–15%) and 3% in the nonsevere LVD group (1 of 40; CL 0.3–8%; P = 0.03), but from 1985 onward, the hospital mortality was 0% for both groups.

The authors concluded that “long-term survival of patients with severe LVD improved progressively and by about 1985 was comparable with that of patients with nonsevere LVD; hospital mortality decreased to a comparable value” and “early and late survival was also good and did not change appreciably over the experience in patients with LV function.” The authors point out that their study demonstrates that “aortic valve surgery in patients with chronic AR and cardiomyopathy is no longer a high-risk procedure for which transplantation is a better option.”  They speculate that this may be due to better medical managements with the use of angiotensin-converting enzyme inhibitors and beta blocks as routine therapy, more sophisticated myocardial protection intraoperatively, reduced complications as a result of intraoperative transesophageal echocardiography, improved replacement heart valves, use of new inotropes and availability of postoperative optimal medical therapy and device options, e.g. biventricular synchronous pacing and implantable cardioverter-defibrillators. They note that the study has limitations, such as referral biases, patient selection bias, nonrandomization of LV dysfunction; duration of preoperative AR could not be determined and could have differed between groups, and the results may not be generalizable to other populations since it was a single-institution study. Based on their findings, they conclude that “for the patient who presents late with AR and severe LVD, surgery is the preferred treatment and can be performed with acceptable risk and late survival.”

1. Bhudia SK, McCarthy PM, Kumpati GS, et al. Improved outcomes after aortic valve surgery for chronic aortic regurgitation with severe left ventricular dysfunction. J Am Coll Cardiol 2007;49(13):1465-1471

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Overweight, obesity, and mortality in a large prospective cohort of persons 50 to 71 years old

This prospective study [1] examines the relationship between being overweight as determined by a body mass index (BMI) of 25.0–29.0 and the risk of death from any cause. The study includes a total of 527,265 men (313,047)and women (214,218), ages 50 to 71 years at enrollment in 1995-1996, in the National Institutes of Health –AARP Diet and Health Study who resided in six US states (California, Florida, Louisiana, New Jersey, North Carolina and Pennsylvania). BMI was calculated based on self-reported height and weight. Relative risks and 95 percent confidence intervals were adjusted for age, race or ethnic group, level of education, smoking status, physical activity, and alcohol intake; alternative analyses were conducted to address potential biases related to pre-existing chronic disease and smoking status. During the 10 year follow up, 42,173 men and 19,144 women died. Initially, the results showed an increased risk of death for the highest and lowest categories of BMI among both men and women, in all racial or ethnic groups and at all ages. When only healthy people who had never smoked were analyzed, the risk of death was associated with both overweight and obesity among men and women. The association became even stronger when healthy people aged 50 who had never smoked were analyzed; risk of death increased by 20-40% among overweight persons and by two to three times among obese persons. The risk of death among underweight persons was attenuated. While the data were not presented, weight loss after the age of 50 years was more strongly associated with the risk of death than was weight gain among men and women who were 65 years of age or older. The authors conclude that “excess body weight during midlife, including overweight, is associated with an increased risk of death.” The authors note that “our large cohort enabled us to estimate risks of death according to narrow categories of BMI with great precision and to discern not only an elevated risk for most categories of overweight but also substantially enhanced risk among the obese.”  

1. Adams KF, Schatzkin A, Harris TB et al. Overweight, obesity, and mortality in a large prospective cohort of persons 50 to 71 years old. N Engl J Med 2006;355:763-778.

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