Impaired myocardial perfusion score and inflammatory markers in patients undergoing primary angioplasty for acute myocardial infarction

BACKGROUND: Microcirculatory dysfunction during acute myocardial infarction is mediated by various mechanisms including inflammation, thrombus, or plaque embolization. We hypothesize that patients with acute myocardial infarction and admission Thrombolysis in Myocardial Infarction (TIMI) myocardial perfusion grade (TMP) < 2 had increased inflammatory status as measured by high sensitivity C-reactive protein (hs-CRP). METHODS: From January 2002 to December 2003, 166 patients (178 lesions) were referred for primary percutaneous coronary intervention. Patients were stratified based on pre-PCI TMP < 2 or TMP 2. Univariate and multivariate predictors of in-hospital and 30-day death were determined with logistic regression. RESULTS: Pre-PCI TMP < 2 was found in 66% vs 34% with TMP 2 (P < .001). Hs-CRP levels were high in both groups but not significantly different (37.9 +/- 6 vs 33.7 +/- 6 mg/L, P = .63). Patients with TMP < 2 had higher WBC (12.83 +/-4.55 x 10(-3) vs 10.83 +/- 3.00 x 10(-3), P = .04), lower ejection fraction (40 +/- 11% vs 46 +/- 12%, P < .001), and higher admission CK-MB levels (116 +/- 13 ng/mL vs 55 +/- 13 ng/mL, P = .006). Death occurred in 12% in the poorTMP group vs 1.8% in the good TMP group (P = .03). Advanced age, use of an intra-aortic balloon pump, and elevated admission WBC were independently associated with in-hospital and 30-day death. CONCLUSIONS: High hs-CRP levels were not associated with impaired myocardial perfusion score. Microcirculatory impairment may be related to an increased inflammatory process, independent from high hs-CRP levels.

Use of platelet glycoprotein IIb/IIIa inhibitors in saphenous vein graft percutaneous coronary intervention and clinical outcomes.

Platelet glycoprotein (GP) IIb/IIIa inhibitors are widely used in percutaneous coronary intervention (PCI). Previous studies have suggested that they do not offer benefit in saphenous vein graft PCI. Nonetheless, their use remains widespread during vein graft angioplasty. We retrospectively analyzed 1,537 patients who underwent saphenous vein graft PCI. Patients who received a GP IIb/IIIa inhibitor (n = 941) were compared with those who did not receive any GP IIb/IIIa inhibitor (n = 596). The primary end point was myonecrosis after PCI (creatine kinase-MB level >3 times the upper reference limit). The incidence of myonecrosis after PCI was similar between the group that received GP IIb/IIIa and the group that did not (odds ratio for GP IIb/IIIa use 1.39, 95% confidence interval 0.97 to 2.00, p = 0.07). Propensity-adjusted analysis demonstrated no significant difference in myonecrosis after PCI, in-hospital mortality, Q-wave myocardial infarction, or bleeding (blood transfusion, retroperitoneal bleed, or hematoma) between the 2 groups. In an analysis restricted to patients who were treated with an emboli protection device, GP IIb/IIIa use was not associated with decreased myonecrosis after PCI (this was also the case for patients who were not treated with an emboli protection device). Unadjusted survival (mean follow-up 5.5 +/- 0.1 years) was similar between the group that received GP IIb/IIIa and the group that did not (log-rank test, p = 0.89). There was no difference in survival after adjusting for the propensity to receive a GP IIb/IIIa inhibitor (adjusted odds ratio for GP IIb/IIIa use 0.92, 95% confidence interval 0.69 to 1.23, p = 0.59). In conclusion, adjunctive use of platelet GP IIb/IIIa inhibitors in saphenous vein graft PCI does not appear to be associated with less myonecrosis or improved survival.

Preprocedural statin use is associated with a reduced hazard of postprocedural myonecrosis in patients undergoing rotational atherectomy--a propensity-adjusted analysis.

Incidence of myonecrosis in patients undergoing rotational atherectomy was evaluated by preprocedural statin use. The incidence of any myonecrosis (24.1% vs 52.3%, P < .001) or significant myonecrosis (7.5% vs 21.8%, P < .001) was significantly lower among patients pretreated with statins. This difference remained significant after multivariable and propensity adjustment.

Impaired myocardial perfusion score and inflammatory markers in patients undergoing primary angioplasty for acute myocardial infarction.

BACKGROUND: Microcirculatory dysfunction during acute myocardial infarction is mediated by various mechanisms including inflammation, thrombus, or plaque embolization. We hypothesize that patients with acute myocardial infarction and admission Thrombolysis in Myocardial Infarction (TIMI) myocardial perfusion grade (TMP) < 2 had increased inflammatory status as measured by high sensitivity C-reactive protein (hs-CRP). METHODS: From January 2002 to December 2003, 166 patients (178 lesions) were referred for primary percutaneous coronary intervention. Patients were stratified based on pre-PCI TMP < 2 or TMP 2. Univariate and multivariate predictors of in-hospital and 30-day death were determined with logistic regression. RESULTS: Pre-PCI TMP < 2 was found in 66% vs 34% with TMP 2 (P < .001). Hs-CRP levels were high in both groups but not significantly different (37.9 +/- 6 vs 33.7 +/- 6 mg/L, P = .63). Patients with TMP < 2 had higher WBC (12.83 +/-4.55 x 10(-3) vs 10.83 +/- 3.00 x 10(-3), P = .04), lower ejection fraction (40 +/- 11% vs 46 +/- 12%, P < .001), and higher admission CK-MB levels (116 +/- 13 ng/mL vs 55 +/- 13 ng/mL, P = .006). Death occurred in 12% in the poorTMP group vs 1.8% in the good TMP group (P = .03). Advanced age, use of an intra-aortic balloon pump, and elevated admission WBC were independently associated with in-hospital and 30-day death. CONCLUSIONS: High hs-CRP levels were not associated with impaired myocardial perfusion score. Microcirculatory impairment may be related to an increased inflammatory process, independent from high hs-CRP levels.

Impact of body mass index on outcome in patients undergoing carotid stenting.

The outcomes of patients who underwent carotid artery interventions were evaluated by body mass index (BMI). Although there was no association between BMI and short-term outcomes, patients with small BMIs were susceptible to an exaggerated long-term mortality hazard.

The interaction of vascular inflammation and chronic kidney disease for the prediction of long-term death after percutaneous coronary intervention.

BACKGROUND: Patients with chronic kidney disease frequently have worse outcomes following percutaneous coronary intervention (PCI) compared to patients with normal renal function. Furthermore, they more commonly have elevated serum markers of inflammation, which may be either directly or indirectly associated with a state of accelerated atherosclerosis. We sought to assess the relationship among glomerular filtration rate (GFR), systemic inflammation, and long-term death after PCI. METHODS: In patients undergoing PCI, the intensity of vascular inflammation was measured using baseline ultrasensitive C-reactive protein (us-CRP), and GFR was calculated using the Modification of Diet in Renal Disease formula. Their association with long-term death was compared using multivariate Cox regression analysis including an interaction element for us-CRP and GFR, baseline clinical, biochemical, and angiographic variables. RESULTS: In 4522 patients (mean age 65 +/- 11 years) having undergone PCI, 332 (7.3%) deaths occurred over the median duration of follow-up of 20.1 months (interquartile range 8.5-31.3 months). The mean GFR was 77 +/- 33 mL/min per 1.73 m2 with a median us-CRP of 3.75 mg/L (interquartile range 1.5-10.1 mg/L). Both increasing levels of CRP (log rank P < .001) and decreasing levels of GFR were univariate predictors of long-term death (P < .001). In a multivariate model, both GFR and us-CRP retained independent predictive value for long-term death. CONCLUSION: Although baseline us-CRP and GFR are both independent predictors of long-term death after PCI, in concert, they impart a markedly exaggerated hazard of mortality.

Slow-flow phenomenon during carotid artery intervention with embolic protection devices: predictors and clinical outcome.

OBJECTIVES: The purpose of this research was to define the predictors of the "slow-reflow" phenomenon during carotid artery intervention with filter-type embolic protection devices (EPDs) and to determine its prognostic significance. BACKGROUND: During carotid artery intervention using filter-type EPDs, we have observed cases in which there is angiographic evidence of a significant reduction in antegrade flow in the internal carotid artery proximal to the filter device, termed "slow-flow." The predictors of this phenomenon and its prognostic significance are unknown. METHODS: Using a single-center prospective carotid intervention registry, patients with slow-flow were compared to patients with normal flow during carotid intervention with respect to clinical, procedural, and lesion characteristics, and the 30-day incidence of death and stroke. RESULTS: A total of 414 patients underwent 453 carotid artery interventions using EPDs. Slow-flow occurred in 42 patients (10.1%) undergoing 42 carotid interventions (9.3%), and most commonly occurred after post-stent balloon dilatation (71.4%). Multivariate logistic regression analysis identified the following predictors of slow-flow: recent history (<6 months) of stroke or transient ischemic attack (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.4 to 5.6, p = 0.004), increased stent diameter (OR 1.4, 95% CI 1.02 to 1.94, p = 0.044), and increased patient age (OR 1.05, 95% CI 1.01 to 1.09, p = 0.025). Among patients with slow-flow, the 30-day incidence of stroke or death was 9.5% compared to 2.9% in patients with normal flow (chi-square = 4.73, p = 0.03). This difference was driven by the disparity in the 30-day incidence of stroke (9.5% vs. 1.7%). CONCLUSIONS: Slow-flow during carotid intervention with EPDs is a frequent event that is associated with an excess risk of periprocedural stroke. The association of the phenomenon with clinically symptomatic carotid lesions and use of larger stent diameters suggests that embolization of vulnerable plaque elements may play a pathogenic role.

Effectiveness and safety of bivalirudin during percutaneous coronary intervention in a single medical center.

A recent large-scale, randomized trial demonstrated the noninferiority of a strategy of bivalirudin with provisional glycoprotein (GP) IIb/IIIa inhibition compared with routine GP IIb/IIIa inhibition. There is a paucity of outcome data with bivalirudin use in the setting of real-world experience. We evaluated 6,996 patients who underwent percutaneous coronary intervention between January 2001 and December 2004 to compare early and late outcomes with a bivalirudin-based antithrombotic regimen with those with a heparin-based regimen. Propensity adjustment was performed to correct for baseline differences in patient characteristics. Bivalirudin-based therapy was used in 1,070 patients, heparin only in 801 patients, and heparin plus GP IIb/IIIa inhibitors in 5,125 patients. Compared with patients who received heparin or those who received heparin plus GP IIb/IIIa inhibitors, patients who received bivalirudin had lower incidences of bleeding (blood transfusion rate 1.7% vs 4.0%, p <0.001) and periprocedural myonecrosis (creatine kinase-MB >5 times the upper limit of normal 2.7% vs 4.3%, p = 0.016). Differences in bleeding end points remained significant after adjusting for the propensity to receive bivalirudin, but there was no difference in ischemic events. There was no difference in unadjusted long-term survival rate (log-rank test p = 0.46, total number of deaths 412, mean follow-up 17 months) or in propensity-adjusted long-term survival rate (hazard ratio 1.37, 95% confidence interval 0.90 to 2.08, p = 0.14). Compared with heparin with or without GP IIb/IIIa inhibition, the use of bivalirudin in a large consecutive patient registry at a tertiary care center was associated with fewer bleeding events and no evident increase in the incidence of ischemic complications.

Effect of chronic kidney disease on outcomes after carotid artery stenting.

We performed a single-center retrospective analysis evaluating the effect of chronic kidney disease among patients who underwent carotid artery stenting. The presence of chronic kidney disease is associated with higher periprocedural and 6-month death, stroke, or myocardial infarction after carotid artery stenting.

Incremental benefit of myocardial contrast to combined dipyridamole-exercise stress echocardiography for the assessment of coronary artery disease.

BACKGROUND: Although assessment of myocardial perfusion by myocardial contrast echocardiography (MCE) is feasible, its incremental benefit to stress echocardiography is not well defined. We examined whether the addition of MCE to combined dipyridamole-exercise echocardiography (DExE) provides incremental benefit for evaluation of coronary artery disease (CAD). METHODS AND RESULTS: MCE was combined with DExE in 85 patients, 70 of whom were undergoing quantitative coronary angiography and 15 patients with a low probability of CAD. MCE was acquired by low-mechanical-index imaging in 3 apical views after acquisition of standard resting and poststress images. Wall motion, left ventricular opacification, and MCE components of the study were interpreted sequentially, blinded to other data. Significant (>50%) stenoses were present in 43 patients and involved 69 coronary territories. The addition of qualitative MCE improved sensitivity for the detection of CAD (91% versus 74%, P=0.02) and accurate recognition of disease extent (87% versus 65% of territories, P=0.003), with a nonsignificant reduction in specificity. CONCLUSIONS: The addition of low-mechanical-index MCE to standard imaging during DExE improves detection of CAD and enables a more accurate determination of disease extent.

The relative importance of vascular structure and function in predicting cardiovascular events.

OBJECTIVES: We sought to assess the prognostic utility of brachial artery reactivity (BAR) in patients at risk of cardiovascular events. BACKGROUND: Impaired flow-mediated vasodilation measured by BAR is a marker of endothelial dysfunction. Brachial artery reactivity is influenced by risk factors and is responsive to various pharmacological and other treatments. However, its prognostic importance is uncertain, especially relative to other predictors of outcome. METHODS: A total of 444 patients were prospectively enrolled to undergo BAR and follow-up. These patients were at risk of cardiovascular events, based on the presence of risk factors or known or suspected cardiovascular disease. We took a full clinical history, performed BAR, and obtained carotid intima-media thickness (IMT) and left ventricular mass and ejection fraction. Patients were followed up for cardiovascular events and all-cause mortality. Multivariate Cox regression analysis was performed to assess the independent association of investigation variables on outcomes. RESULTS: The patients exhibited abnormal BAR (5.2 +/- 6.1% [mean +/- SD]) but showed normal nitrate-mediated dilation (9.9 +/- 7.2%) and normal mean IMT (0.67 +/- 0.12 mm [average]). Forty-nine deaths occurred over the median follow-up period of 24 months (interquartile range 10 to 34). Patients in the lowest tertile group of BAR (<2%) had significantly more events than those in the combined group of highest and mid-tertiles (p = 0.029, log-rank test). However, mean IMT (rather than flow-mediated dilation) was the vascular factor independently associated with mortality, even in the subgroup (n = 271) with no coronary artery disease and low risk. CONCLUSIONS: Brachial artery reactivity is lower in patients with events, but is not an independent predictor of cardiovascular outcomes in this cohort of patients.

Noninvasive tests for arterial structure, function, and compliance: do they identify risk or diagnose disease?

BACKGROUND: Brachial artery reactivity (BAR), carotid intima-media thickness (IMT), and applanation tonometry for evaluation of total arterial compliance may provide information about preclinical vascular disease. We sought to determine whether these tests could be used to identify patients with coronary artery disease (CAD) without being influenced by their ability to identify those at risk for CAD developing. METHODS: We studied 100 patients and compared 3 groups: 35 patients with known CAD; 34 patients with symptoms and risk factors but no CAD identified by stress echocardiography (risk group); and 31 control subjects. BAR and IMT were measured using standard methods, and total arterial compliance was calculated by the pulse-pressure method from simultaneous radial applanation tonometry and pulsed wave Doppler of the left ventricular outflow. Ischemia was identified as a new or worsening wall-motion abnormality induced by stress. RESULTS: In a comparison between the control subjects and patients either at risk for developing CAD or with CAD, the predictors of risk for CAD were: age (P =.01); smoking history (P =.002); hypercholesterolemia (P =.002); and hypertension (P =.004) (model R = 0.82; P =.0001). The independent predictors of CAD were: IMT (P =.001); BAR (P =.04); sex (P =.005); and hypertension (P =.005) (model R = 0.80; P =.0001). CONCLUSION: IMT, BAR, and traditional cardiovascular risk factors appear to identify patients at risk for CAD developing. However, only IMT was significantly different between patients at risk for developing CAD and those with overt CAD.

The effect of long-term aggressive lipid lowering on ischemic and atherosclerotic burden in patients with chronic kidney disease.

BACKGROUND: Cardiac mortality is the main cause of death in patients with chronic kidney disease (CKD). In this study, we sought the efficacy of long-term intensive lipid level lowering on atherosclerotic burden in patients with CKD. METHODS: Patients with CKD (n = 38; age, 64 +/- 11 years) and a similar group of patients with coronary artery disease (CAD; n = 31) were treated prospectively with atorvastatin, up to 80 mg/d. Lipid profile, carotid intima-media thickness (IMT; a marker of atherosclerotic burden), and dobutamine echocardiography were measured at baseline and 2 years. Predictors of change in maximal IMT were sought in a linear model. RESULTS: Despite similar cholesterol level lowering, patients with CAD showed an improvement in maximum IMT, whereas those with CKD did not (mean between-group difference, 0.07 mm; 95% confidence interval, 0.01 to 0.12). Change in maximal IMT was associated with kidney disease (R2 = 0.09; P = 0.013), smoking (R2 = 0.083; P = 0.017), baseline low-density lipoprotein cholesterol (LDL-C) level (R2 = 0.064; P = 0.045), very low density cholesterol (VLDL-C) level (R2 = 0.084; P = 0.021), and calcium channel blocker use (R2 = 0.094; P = 0.01). In a multivariate model, kidney disease and baseline LDL-C and VLDL-C levels remained independent predictors of change in maximal IMT (model R2 = 0.24; P = 0.004). Only patients with CAD decreased their number of ischemic segments (2.5 +/- 1.4 to 1.2 +/- 1.5 segments; P = 0.002). Overall change in ischemic segment number correlated with change in maximal IMT (r = 0.32; P = 0.019). CONCLUSION: Patients with CKD undergoing intensive lipid level lowering do not show the same changes in atherosclerotic or ischemic burden as patients with CAD. Independent predictors of change in maximal IMT were CKD and baseline LDL-C and VLDL-C levels.

Effects of revascularisation and contractile reserve on left ventricular remodelling in patients with impaired left ventricular function.

OBJECTIVE: We sought to define the influence of revascularisation and contractile reserve on left ventricular (LV) remodelling in patients with LV dysfunction after myocardial infarction. Revascularisation of viable myocardium is associated with improved regional function, but the effect on remodelling is undefined. METHODS: We studied 70 patients with coronary artery disease and LV dysfunction, 31 of whom underwent revascularisation. A standard dobutamine stress echocardiogram (DbE) was carried out. All patients underwent standard medical treatment; the decision to revascularise was made clinically, independent of this study. LV volumes and ejection fraction were measured by 3D echocardiography at baseline and after an average of 40 weeks. RESULTS: There was no significant difference in baseline ejection fraction or volumes between patients who underwent revascularisation and the remainder. Compared to medically treated patients, revascularised patients had significant improvements in ejection fraction and end-systolic volume in follow-up. The impact of baseline variables on remodelling was assessed by dividing patients into tertiles of LV ejection fraction and volumes. Revascularised patients in the lowest tertile of ejection fraction at baseline (<38%) had a significant improvement in end-systolic volume and ejection fraction, larger than obtained in medically treated patients with low ejection fraction. Revascularised patients with an ejection fraction >38% did not show significant improvement in volumes compared to baseline. Revascularised patients in the largest tertiles of end-systolic (>88 ml) or end-diastolic volume (>149 ml) at baseline had a significant improvement in end-systolic volume. CONCLUSION: Remodeling appears to occur independent of the presence of regional contractile reserve but does correlate with the volume response to low-dose dobutamine.

Independent contribution of plaque complexity to myocardial ischemia during dobutamine stress echocardiography.

The influence of complex plaque morphology on the extent of demand-induced ischemia in unselected patients is not well defined. We sought to investigate the functional significance of lesion morphology in patients who underwent coronary angiography and dobutamine stress echocardiography (DSE). Angiography and DSE were performed within a 6-month period (mean 1 +/- 1 month) in 196 patients. Angiographic assessments involved quantification of stenosis severity, assessment of the extent of jeopardized myocardium, and categorization of plaque morphology according to the Ambrose classification. DSE was interpreted by separate investigators with respect to wall motion score index (WMSI) and number of coronary territories involved. A general linear model was constructed to assess the independent contribution of patient characteristics and angiographic and DSE results with respect to extent of ischemic myocardium. Complex lesion morphology was seen in 62 patients (32%). Patients with complex lesions were more likely to have had prior myocardial infarction (p <0.001) and be current smokers (p = 0.03). During angiography, they exhibited a trend toward a greater number of diseased vessels, had a greater coronary jeopardy score (p <0.001) and more frequent collateral flow (p = 0.03). During echocardiography, patients had a higher stress WMSI (p <0.001) and were more likely to show ischemia in all 3 arterial territories (p <0.01). On multivariate regression, the coronary artery jeopardy score and the presence of complex plaque morphology were independent predictors of the extent of ischemic myocardium (R(2) = 34%, p <0.001). Thus, patients with complex plaque morphology are older, more likely to smoke, and more likely to have had prior myocardial infarction. They exhibit more extensive disease with higher coronary jeopardy scores and a higher resting and peak stress WMSI. Despite these differences, complex plaque morphology remains an independent predictor of the extent of ischemia during stress.

Correlates of subclinical left ventricular dysfunction in ESRD.

BACKGROUND: Abnormalities of the left ventricle are common in patients with end-stage renal disease (ESRD) both before and after the start of renal replacement therapy. The purpose of this study is to identify possible causes of subclinical left ventricular (LV) dysfunction in patients with ESRD. In particular, we sought to determine whether the presence of ESRD was itself associated with dysfunction independent of LV hypertrophy and coronary artery disease. METHODS: Assessment of cardiovascular risk factors and dialysis adequacy was completed in 145 unselected patients with ESRD who were recruited from the renal dialysis unit and compared with age- and sex-matched controls. Among the 68 patients with ESRD who had undergone a dobutamine stress echocardiogram with normal findings, regional cardiac function was quantified by myocardial Doppler velocity, LV volumes and mass were measured using three-dimensional echocardiography, and vascular function was assessed using brachial artery reactivity (BAR). RESULTS: LV diastolic velocity was impaired in patients with ESRD, but there was no significant difference in systolic velocity compared with control patients of similar age. Age, diabetes mellitus, hypertension, and LV mass were independent predictors of diastolic velocity (model R2 = 0.45; P < 0.001), whereas age and risk factor number were predictors of systolic velocity (model R2 = 0.19; P = 0.002). Increasing risk factor number had no significant relationship with LV mass or volume. There was no detected association between BAR and incremental risk factors (P = 0.51). CONCLUSION: Subclinical LV dysfunction occurs in patients with ESRD, but is evidenced as abnormal myocardial diastolic, rather than systolic, function. Correlates of abnormal function are age, diabetes mellitus, hypertension, and LV mass, rather than ESRD alone, dialysis adequacy, or abnormal endothelial function.

A randomized trial of aggressive lipid reduction for improvement of myocardial ischemia, symptom status, and vascular function in patients with coronary artery disease not amenable to intervention.

PURPOSE: To determine the effects of aggressive lipid lowering on markers of ischemia, resistance vessel function, atherosclerotic burden, and symptom status in patients with symptomatic coronary artery disease. METHODS: Sixty consecutive patients with coronary artery disease that was unsuitable for revascularization were assigned randomly to either usual therapy of lipids for patients with a low-density lipoprotein (LDL) cholesterol target level <116 mg/dL, or to a more aggressive lipid-lowering strategy involving up to 80 mg/d of atorvastatin, with a target LDL cholesterol level <77 mg/dL. The extent and severity of inducible ischemia (by dobutamine echocardiography), vascular function (brachial artery reactivity), atheroma burden (carotid intima-media thickness), and symptom status were evaluated blindly at baseline and after 12 weeks of treatment. RESULTS: After 12 weeks of treatment, patients in the aggressive therapy group had a significantly greater decrease in mean (+/- SD) LDL cholesterol level than those in the usual care group (29 +/- 38 mg/dL vs. 7 +/- 24 mg/dL, P = 0.03). Patients in the aggressive therapy group had a reduction in the number of ischemic wall segments (mean between-group difference of 1.3; 95% confidence interval: 0.1 to 2.0; P = 0.04), flow-mediated dilatation (mean between-group difference of 5.9%; 95% confidence interval: 2.5% to 9.4%; P = 0.001), and angina score after 12 weeks. There were no significant changes in atherosclerotic burden in either group. CONCLUSION: Patients with symptomatic coronary artery disease who are treated with aggressive lipid lowering have improvement of symptom status and ischemia that appears to reflect improved vascular function but not atheroma burden.