Igor F. Palacios

Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture.

BackgroundRupture of atherosclerotic plaques is probably the most important mechanism underlying the sudden onset of acute coronary syndromes. Macrophages may release lytic enzymes that degrade the fibrous cap and therefore produce rupture of the atherosclerotic plaque. This study was designed to quantify macrophage content in coronary plaque tissue from patients with stable and unstable coronary syndromes. Methods and ResultsHematoxylin and eosin and immuno-staining with anti-human macrophage monoclonal antibody (PG-M1) were performed. Computerized planimetry was used to analyze 26 atherectomy specimens comprising 524 pieces of tissue from 8 patients with chronic stable angina, 8 patients with unstable angina, and 10 patients with non-Q-wave myo-cardial infarction. Total plaque area was 417±87 mm2× 10−2 in patients with stable angina, 601±157 mm2×10−2 in patients with unstable angina, and 499±87 mm2× 10−2in patients with non-Q-wave myocardial infarction (P=NS). The macrophage-rich area was larger in plaques from patients with unstable angina (61±18 mm2x 102) and non-Q-wave myocardial infarction (87±32 mm2× 10−2) than in plaques from patients with stable angina (14±5 mm2×10−2) (P=.024). The percentage of the total plaque area occupied by macrophages was also larger in patients with unstable angina (13.3 ±5.6%) and non-Q-wave myocardial infarction (14.6±4.6%) than in patients with stable angina (3.14±1%) (P=.018). Macrophagerich sclerotic tissue was largest in patients with non-Q-wave myocardial infarction (67±30 mm2× 1010−2) and unstable angina (55±19 mm2× 10−2) than in patients with stable angina (11.5±4.1 mm2× 10−2) (P=.046). Macrophage-rich atheromatous gruel was also larg-est in patients with non-Q-wave myocardial infarction (15±4 mm2×10−2) than in patients with unstable angina (3.3±1.7 mm2×10−2) or stable angina (2.4±1.2 mm2× 10−2) (P=.026). ConclusionsMacrophage-rich areas are more frequently found in patients with unstable angina and non-Q-wave myocardial infarction. This suggests that macrophages are a marker of unstable atherosclerotic plaques and may play a significant role in the pathophysiology of acute coronary syndromes.

Percutaneous balloon dilatation of the mitral valve: an analysis of echocardiographic variables related to outcome and the mechanism of dilatation.

Twenty two patients (four men, 18 women, mean age 56 years, range 21 to 88 years) with a history of rheumatic mitral stenosis were studied by cross sectional echocardiography before and after balloon dilatation of the mitral valve. The appearance of the mitral valve on the pre-dilatation echocardiogram was scored for leaflet mobility, leaflet thickening, subvalvar thickening, and calcification. Mitral valve area, left atrial volume, transmitral pressure difference, pulmonary artery pressure, cardiac output, cardiac rhythm, New York Heart Association functional class, age, and sex were also studied. Because there was some increase in valve area in almost all patients the results were classified as optimal or suboptimal (final valve area less than 1.0 cm2, final left atrial pressure greater than 10 mm Hg, or final valve area less than 25% greater than the initial area). The best multiple logistic regression fit was found with the total echocardiographic score alone. A high score (advanced leaflet deformity) was associated with a suboptimal outcome while a low score (a mobile valve with limited thickening) was associated with an optimal outcome. No other haemodynamic or clinical variables emerged as predictors of outcome in this analysis. Examination of pre-dilatation and post-dilatation echocardiograms showed that balloon dilatation reliably resulted in cleavage of the commissural plane and thus an increase in valve area.

Active myocarditis in the spectrum of acute dilated cardiomyopathies: clinical features, histologic correlates, and clinical outcome

We studied the clinical features and course (average follow-up time, 18 months) of 27 patients with acute dilated cardiomyopathy (symptoms for less than 6 months) who were referred for endomyocardial biopsy. Almost 40 per cent of the patients subsequently had a rise in left ventricular ejection fraction (on average, from 0.21 to 0.41) and substantial improvement in heart failure; the remainder died or had chronic dilated cardiomyopathy. Biopsy revealed myocarditis in 18 patients, and this finding was especially common (89 per cent) in patients who had been ill for less than four weeks. But the biopsy specimen was negative in four patients whose clinical features and later course were diagnostic of myocarditis. Nine patients received immunosuppressive drugs, and four improved--a rate that did not differ from the rate of spontaneous improvement. Neither the histologic features of the biopsy specimen nor the clinical features at presentation were clearly correlated with subsequent improvement, whether or not immunosuppressive drugs were given. We conclude that many cases of unexplained dilated cardiomyopathy result from myocarditis. Definitive histologic confirmation depends on the duration of illness. The efficacy of immunosuppressive treatment must still be established.

Argentine Randomized Study: Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple-Vessel Disease (ERACI II): 30-Day and One-Year Follow-up Results

OBJECTIVE The purpose of this study was to compare percutaneous transluminal coronary revascularization (PTCR) employing stent implantation to conventional coronary artery bypass graft surgery (CABG) in symptomatic patients with multivessel coronary artery disease. BACKGROUND Previous randomized studies comparing balloon angioplasty versus CABG have demonstrated equivalent safety results. However, CABG was associated with significantly fewer repeat revascularization procedures. METHODS A total of 2,759 patients with coronary artery disease were screened at seven clinical sites, and 450 patients were randomly assigned to undergo either PTCR (225 patients) or CABG (225 patients). Only patients with multivessel disease and indication for revascularization were enrolled. RESULTS Both groups had similar clinical demographics: unstable angina in 92%; 38% were older than 65 years, and 23% had a history of peripheral vascular disease. During the first 30 days, PTCR patients had lower major adverse events (death, myocardial infarction, repeat revascularization procedures and stroke) compared with CABG patients (3.6% vs. 12.3%, p = 0.002). Death occurred in 0.9% of PTCR patients versus 5.7% in CABG patients, p < 0.013, and Q myocardial infarction (MI) occurred in 0.9% PTCR versus 5.7% of CABG patients, p < 0.013. At follow-up (mean 18.5 +/- 6.4 months), survival was 96.9% in PTCR versus 92.5% in CABG, p < 0.017. Freedom from MI was also better in PTCR compared to CABG patients (97.7% vs. 93.4%, p < 0.017). Requirements for new revascularization procedures were higher in PTCR than in CABG patients (16.8% vs. 4.8%, p < 0.002). CONCLUSIONS In this selected high-risk group of patients with multivessel disease, PTCR with stent implantation showed better survival and freedom from MI than did conventional surgery. Repeat revascularization procedures were higher in the PTCR group.

Sex Differences in Medical Care and Early Death After Acute Myocardial Infarction

Background— Women receive less evidence-based medical care than men and have higher rates of death after acute myocardial infarction (AMI). It is unclear whether efforts undertaken to improve AMI care have mitigated these sex disparities in the current era. Methods and Results— Using the Get With the Guidelines–Coronary Artery Disease database, we examined sex differences in care processes and in-hospital death among 78 254 patients with AMI in 420 US hospitals from 2001 to 2006. Women were older, had more comorbidities, less often presented with ST-elevation myocardial infarction (STEMI), and had higher unadjusted in-hospital death (8.2% versus 5.7%; P<0.0001) than men. After multivariable adjustment, sex differences in in-hospital mortality rates were no longer observed in the overall AMI cohort (adjusted odds ratio [OR]=1.04; 95% CI, 0.99 to 1.10) but persisted among STEMI patients (10.2% versus 5.5%; P<0.0001; adjusted OR=1.12; 95% CI, 1.02 to 1.23). Compared with men, women were less likely to receive early aspirin treatment (adjusted OR=0.86; 95% CI, 0.81 to 0.90), early &bgr;-blocker treatment (adjusted OR=0.90; 95% CI, 0.86 to 0.93), reperfusion therapy (adjusted OR=0.75; 95% CI, 0.70 to 0.80), or timely reperfusion (door-to-needle time ≤30 minutes: adjusted OR=0.78; 95% CI, 0.65 to 0.92; door-to-balloon time ≤90 minutes: adjusted OR=0.87; 95% CI, 0.79 to 0.95). Women also experienced lower use of cardiac catheterization and revascularization procedures after AMI. Conclusions— Overall, no sex differences in in-hospital mortality rates after AMI were observed after multivariable adjustment. However, women with STEMI had higher adjusted mortality rates than men. The underuse of evidence-based treatments and delayed reperfusion among women represent potential opportunities for reducing sex disparities in care and outcome after AMI.

Coronary Composition and Macrophage Infiltration in Atherectomy Specimens From Patients With Diabetes Mellitus

BackgroundLipid-rich, inflamed atherosclerotic lesions are associated with plaque rupture and thrombosis, which are the most important causes of death in patients with diabetes mellitus. This study was designed to quantify lipid composition and macrophage infiltration in the coronary lesions of patients with diabetes mellitus. Methods and ResultsA total of 47 coronary atherectomy specimens from patients with diabetes mellitus were examined and compared with 48 atherectomy specimens from patients without diabetes. Plaque composition was characterized by trichrome staining. Macrophage infiltration was characterized by immunostaining. Clinical and demographic data were similar in both groups. The percentage of total area occupied by lipid-rich atheroma was larger in specimens from patients with diabetes (7±2%) than in specimens from patients without diabetes (2±1%;P =0.01), and the percentage of total area occupied by macrophages was larger in specimens from patients with diabetes (22±3%) than in specimens from patients without diabetes (12±1%;P =0.003). The incidence of thrombus was also higher in specimens from patients with diabetes than in specimens from patients without diabetes (62% versus 40%;P =0.04). Plaque composition, macrophage infiltration, and thrombus were similar in lesions from diabetic patients treated with insulin compared with lesions from patients treated with sulfonylureas or diet. ConclusionsCoronary tissue from patients with diabetes exhibits a larger content of lipid-rich atheroma, macrophage infiltration, and subsequent thrombosis than tissue from patients without diabetes. These differences suggest an increased vulnerability for coronary thrombosis in patients with diabetes mellitus.

Macrophages, Smooth Muscle Cells, and Tissue Factor in Unstable Angina Implications for Cell-Mediated Thrombogenicity in Acute Coronary Syndromes

Background Macrophage expression of tissue factor may be responsible for coronary thrombogenicity in patients with plaque rupture. In patients without plaque rupture, smooth muscle cells may be the thrombogenic substrate. This study was designed to identify the cellular correlations of tissue factor in patients with unstable angina. Methods and Results Tissue from 50 coronary specimens (1560 pieces) from patients with unstable angina and 15 specimens from patients with stable angina were analyzed. Total and segmental areas (in square millimeters) were identified with trichrome staining. Macrophages, smooth muscle cells, and tissue factor were identified by immunostaining. Tissue factor content was larger in unstable angina (42±3%) than in stable angina (18±4%) ( P =.0001). Macrophage content was also larger in unstable angina (16±2%) than in stable angina (5±2%) ( P =.002). The percentage of tissue factor located in cellular areas was larger in coronary samples from patients with unstable angina (67±8%) than in samples from patients with stable angina (40±5%) ( P =.00007). Multiple linear stepwise regression analysis showed that coronary tissue factor content correlated significantly ( r =.83, P r =.98, P Conclusions Tissue factor content is increased in unstable angina and correlates with areas of macrophages and smooth muscle cells, suggesting a cell-mediated thrombogenicity in patients with acute coronary syndromes.

Percutaneous balloon valvotomy for patients with severe mitral stenosis.

Thirty-five patients with severe mitral stenosis underwent percutaneous mitral valvotomy (PMV). There were 29 female and six male patients (mean age 49 +/- 3 years, range 13 to 87). After transseptal left heart catheterization, PMV was performed with either a single- (20 patients) or double- (14 patients) balloon dilating catheter. Hemodynamic and left ventriculographic findings were evaluated before and after PMV. There was one death. Mitral regurgitation developed or increased in severity in 15 patients (43%). One patient developed complete heart block requiring a permanent pacemaker. PMV resulted in a significant decrease in mitral gradient from 18 +/- 1 to 7 +/- 1 mm Hg (p less than .0001) and a significant increase in both cardiac output from 3.9 +/- 0.2 to 4.6 +/- 0.2 liters/min (p less than .001) and in mitral valve area from 0.8 +/- 0.1 to 1.7 +/- 0.2 cm2 (p less than .0001) Effective balloon dilating diameter per square meter of body surface area correlated significantly with the decrease in mitral gradient but did not correlate with the degree of mitral regurgitation. There was no correlation of age, prior mitral commissurotomy or mitral calcification with hemodynamic results. PMV is an effective nonsurgical procedure for patients with mitral stenosis, including those with pliable valves, those with previous commissurotomy, and even those with mitral calcification.

Dilated Cardiomyopathies of the Adult

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Macrophages, Smooth Muscle Cells, and Tissue Factor in Unstable Angina

BACKGROUND Macrophage expression of tissue factor may be responsible for coronary thrombogenicity in patients with plaque rupture. In patients without plaque rupture, smooth muscle cells may be the thrombogenic substrate. This study was designed to identify the cellular correlations of tissue factor in patients with unstable angina. METHODS AND RESULTS Tissue from 50 coronary specimens (1560 pieces) from patients with unstable angina and 15 specimens from patients with stable angina were analyzed. Total and segmental areas (in square millimeters) were identified with trichrome staining. Macrophages, smooth muscle cells, and tissue factor were identified by immunostaining. Tissue factor content was larger in unstable angina (42 +/- 3%) than in stable angina (18 +/- 4%) (P = .0001). Macrophage content was also larger in unstable angina (16 +/- 2%) than in stable angina (5 +/- 2%) (P = .002). The percentage of tissue factor located in cellular areas was larger in coronary samples from patients with unstable angina (67 +/- 8%) than in samples from patients with stable angina (40 +/- 5%) (P = .00007). Multiple linear stepwise regression analysis showed that coronary tissue factor content correlated significantly (r = .83, P < .0001) with macrophage and smooth muscle cell areas only in tissue from patients with unstable angina, with a strong relationship between tissue factor content and macrophages in the atheromatous gruel (r = .98, P < .0001). CONCLUSIONS Tissue factor content is increased in unstable angina and correlates with areas of macrophages and smooth muscle cells, suggesting a cell-mediated thrombogenicity in patients with acute coronary syndromes.