Histological evaluation of coronary plaque in patients with variant angina: relationship between vasospasm and neointimal hyperplasia in primary coronary lesions

OBJECTIVES: This study was designed to determine whether coronary vasospasm in patients with variant angina pectoris (VAP) may produce focal organic lesions at the site of vasospasm that would contribute to disease progression. BACKGROUND: Recent clinical angiographic and experimental studies have demonstrated the potential role of vasospasm in the worsening of organic coronary stenosis. METHODS: We studied histologically the coronary plaques obtained at atherectomy in 202 patients with moderate to severe coronary stenosis. This population included 22 patients with VAP, 100 patients with chronic stable angina and 80 patients with restenosis following angioplasty or atherectomy. Diagnosis of VAP was based on both the clinical feature of angina at rest associated with ST elevation and a positive response to acetylcholine provocation test. RESULTS: The most common histological appearance in 92% of patients with stable angina was hypocellular fibroatheromatous plaques, whereas neointimal hyperplasia was the characteristic feature of the plaque observed in 90% of patients with restenosis. The coronary specimens at the site of spasm in 15 of the 22 patients (68%) with VAP demonstrated intimal injuries such as neointimal hyperplasia (15), thrombus formation (2), and intimal hemorrhage (3). Neointimal hyperplasia was significantly more common in the patients with VAP as compared with those with stable angina (68% vs. 8%; p < 0.0001). A rapid progression of organic stenosis within three years was angiographically found in 5 of the 22 patients with variant angina. In all five cases, neointimal hyperplasia was the main contributor to the worsening of the organic lesion at the site of spasm. These histological findings in patients with VAP extremely resembled those in restenosis. Except for vasospasm, no factors significantly predicted the presence of neointimal formations in primary coronary lesions. CONCLUSIONS: Coronary vasospasm may provoke vascular injury that leads to the formation of neointima in VAP patients similar to that seen with restenosis. Coronary spasm may thus play a key role in the rapid coronary stenosis progression in certain patients with VAP.     

Intracoronary artery thrombus formation in unstable angina: a clinical, biochemical and angiographic correlation

OBJECTIVES: We examined the relation between the level of urinary fibrinopeptide A and the presence of angiographic intracoronary thrombus in patients with unstable angina to determine whether this marker predicts active thrombus formation. BACKGROUND: Although it is known that thrombus plays a role in acute ischemic syndromes, a noninvasive method to predict its presence in individual patients with unstable angina has not been determined. Fibrinopeptide A is a polypeptide cleaved from fibrinogen by thrombin and thus is a sensitive marker of thrombin activity and fibrin generation. METHODS: Angiographic thrombus, graded 0 to 4, and the presence of ST segment depression or T wave inversions, or both, on the electrocardiogram (ECG) were related to fibrinopeptide A levels in 24 patients with rest angina of new onset, 18 with crescendo angina, 19 with stable angina and 9 with chest pain but without coronary artery disease. All patients had chest pain within the 24 h of sample acquisition. RESULTS: The angiographic incidence of thrombus was significantly higher in patients with new onset of rest angina (67%, p < 0.001) and crescendo angina (50%, p < 0.001) as were fibrinopeptide A levels (p = 0.002). Fibrinopeptide A levels correlated significantly (p < 0.001) with the presence of a filling defect (grade 4 intracoronary thrombus) or contrast staining (grade 3). All patients with fibrinopeptide A > or = 8 ng/mg creatinine showed grade 3 to 4 thrombus and 15 of 16 patients with levels > or = 6.0 ng/mg creatinine exhibited angiographic evidence of thrombus (13 with grades 3 to 4). Patients with reversible ST changes on the ECG had significantly higher levels of fibrinopeptide A (p < 0.001), and ST changes correlated significantly with the presence of angiographic thrombus (p < 0.001). Nonetheless, a significant minority of patients with unstable angina had neither angiographic nor biochemical evidence of thrombus. CONCLUSIONS: Elevated fibrinopeptide A levels in unstable angina reflected active intracoronary thrombus formation and were present in patients with angina of new onset as well as crescendo angina. Reversible ST changes are accompanied by thrombin activity and angiographic thrombus formation. However, a sizable percentage of patients with unstable angina had no evidence of thrombus and these patients may have had transient platelet aggregation without fibrin thrombus formation.     

Long-term (10-year) outcome in patients with unstable angina pectoris treated by coronary balloon angioplasty

OBJECTIVES: We sought to examine completed 10-year survival and event-free survival in patients with stable and unstable angina pectoris treated by coronary balloon angioplasty. BACKGROUND: Patients with unstable angina are at increased risk for recurrent acute coronary events. METHODS: The study included 208 consecutive patients (133 with stable and 75 with unstable angina pectoris) undergoing angioplasty from 1984 to 1986. The balloon crossed the lesion in 185 patients (121 with stable and 64 with unstable angina pectoris). Angioplasty was performed in patients with unstable angina pectoris 12+/-15 days (median 8) after symptom onset. Patients with unstable angina pectoris were classified retrospectively into Braunwald class I (n=3), class II (n=20), class III (n=28), class B (n=52) and class C (n=12). Follow-up data were obtained from hospital charts, telephone interview and official death certificates where applicable. The study had >80% power to detect a clinically significant 20% difference in survival and a 20% difference in event-free survival between the stable and unstable patient groups. RESULTS: Despite similar baseline characteristics, early (40-day) mortality was slightly higher in patients with unstable angina (4.7% [3 of 64 patients] vs. 0.8% [1 of 121 patients], p=NS). Long-term outcome was not different, because survival curves were parallel thereafter (10-year survival was 83% for those with stable and 77% for those with unstable angina, p=NS). Survival free of myocardial infarction or coronary artery bypass graft surgery at 10 years was 53% in patients with stable and 47% in patients with unstable angina (p=NS), and survival free of infarction, bypass surgery or repeat angioplasty was 32% for both groups at 10 years. In patients with Braunwald class III unstable angina, 10-year survival was 80%, as compared with 85% in other patients with unstable angina, due to the early hazard (p=NS). Survival and event-free survival were similar in patients who had had a recent myocardial infarction (Braunwald class C) and in patients with acute electrocardiographic changes. Repeat hospital admissions were not more frequent in patients with unstable angina (3.1+/-3.5 vs. 3.0+/-2.6, p=NS). CONCLUSIONS: Ten-year survival and event-free survival were similar in patients with stable and unstable angina pectoris treated by coronary balloon angioplasty, with no evidence of an increased rate of recurrent cardiovascular events in the unstable group.     

Management of patients with unstable angina in a general cardiology unit

AIMS: To review the clinical management of patients with unstable angina and to relate prospectively initial risk stratification, according to the Braunwald criteria, to subsequent cardiovascular events. METHODS: From February to April 1996 we performed a three month prospective review of all patients with a diagnosis of unstable angina admitted to the coronary care unit at Auckland Hospital. RESULTS: One hundred and four patients (61% male), with a mean age of 64 years, were classified as high (58%), intermediate (41%) or low risk (1%) for an adverse cardiac event. Twelve (12%) patients had a documented myocardial infarction, of whom 11 were in the high-risk group (p = 0.038). During hospitalisation there was one death. Twelve (12%) patients underwent inpatient exercise testing, five of whom proceeded to a coronary angiogram prior to hospital discharge. Twenty-two (21%) unstable patients underwent inpatient angiography without prior exercise testing. Twenty-one (20%) patients required revascularisation on the same admission: percutaneous coronary angioplasty (n = 14) or coronary artery bypass grafting (n = 7). Twelve of these 21 patients were in the high-risk group (p = 0.999, NS). CONCLUSION: Patients admitted with unstable angina had low inpatient mortality but a 12% rate of subsequent myocardial infarction. Braunwald low-risk unstable angina patients were not admitted to the coronary care unit. Braunwald high-risk patients were more likely to develop a subsequent myocardial infarction. Stratification of patients into intermediate or high-risk groups did not relate to initial medical management or subsequent revascularisation. Thus, while this method of risk stratification may predict cardiovascular events, it may be of limited clinical use in the New Zealand environment.     

Low-dose theophylline increases urine output in diuretic-dependent critically ill children

BACKGROUND: The pathogenesis of unstable angina involves the presence of intracoronary thrombus which may have potential bearing on the therapeutic efficacy of intracoronary stenting to reduce acute complications and restenosis rate. METHODS: In order to evaluate in-hospital and long-term outcome of coronary stenting in patients with unstable angina, we retrospectively examined our experience in 311 consecutive patients. Braunwald class III angina (B or C) was present in 35% of the cases. Three hundred seventy one stents were implanted in 315 lesions, most of them (62.4%) with complex morphology. Angiography identified an intraluminal thrombus in 22 target sites. Stent indication was elective in 146 cases (46.9%), for suboptimal results in 149 (47.9%) and for bail-out in 16 (5%). RESULTS: Procedural success was obtained in 96.3% of the study population. Major complications occurred in 12 (3.7%) patients: myocardial infarction in 6 (1.9%) cases, emergency bypass surgery in 3 (0.9%) and death in 3 (0.9%), none of them related to acute stent thrombosis. Vascular complications occurred in 5 patients (1.6%). The mean hospital stay after stenting was 2.8 +/- 1.6 days. Subacute stent thrombosis occurred in one patient and led to a Q-wave anterior myocardial infarction. Follow-up (9 +/- 5 months) status was ascertained in 216 patients and revealed an overall clinical success rate of 87.3%. Restenosis occurred in 23.5% of 157 patients who underwent angiographic follow-up. Late events included 3 non-fatal myocardial infarction, 6 new PTCA, 3 elective bypass surgery and 1 cardiac death. CONCLUSIONS: Intracoronary stenting appears safe and effective in patients with unstable angina, despite the presence of a thrombogenic milieu. Optimal immediate angiographic results, related to the mechanical properties of stents, together with a vigorous antithrombotic regimen, contributes to the favorable outcomes in this adverse setting.     

Clinical experience with AVE Micro Stent. Results of the implantation of 204 stents

To assess the efficacy and safety of the AVE Micro Stent, we deployed 204 stents in 144 consecutive patients during a one year period. Indications for stenting were acute closure in 3.4%, dissection in 5.4%, post balloon pTCA restenosis in 3.4%, non-favorable result in 16.7% and de novo in 71.1%. Patient population included 39 (27%) patients with stable angina, 86 (59.7%) with unstable angina, 16 (11.1%) with acute MI and 3 (2.1%) with cardiogenic shock. Angiographic lesion morphology were as follows: type A, 17.7%, type B1, 42.1%; type B2, 16.2%; type C, 24%. Procedural success was obtained in 204 of 205 attempted stents (99.5%) and clinical success was 93.1%. Oral anticoagulation was not routinely used. Enzymatic elevation consistent with myocardial necrosis occurred in 3.2% with Q wave MI in 0.7%. Three patients (2.1%) had bleeding at site of femoral puncture with one requiring transfusion and surgery. Mortality was 0.8% in the angina group, 6.25% in the MI group and one of the 3 patients with cardiogenic shock died and represents the only apparent stent thrombosis as she experienced sudden death one week after successful left main stenting. We conclude that high success rates can be obtained with the AVE Micro Stent due to it's excellent trackability, adequate radio-opacity and relative flexibility.     

Epidural and intrathecal n-butyl-p-aminobenzoate solution in the rat. Comparison with bupivacaine

Lipoprotein(a) [Lp(a)] has been proposed as a restenosis risk factor, but it is not known if Lp(a) is present in the injured arterial wall during the initial neointimal growth. The purpose of this study was to determine if Lp(a) is incorporated into the vessel wall during rapid neointimal formation after arterial injury in primates. In this model, distention of the iliac artery with an angioplasty catheter caused focal breaks in the internal elastic lamina (IEL) in 80% of the vessels and extensive IEL fragmentation with medial disruption in 20% of the vessels. Neointimal growth was noted in all injured arteries; thrombus formation was noted in 40% of the vessels. Based on morphometric measurements, injured arteries had neointimal areas of 0.41 +/- 0.05 (n = 4) and 0.83 +/- 0.23 (n = 6) mm2 at 14 and 28 days after injury, respectively. Control arteries had an intact IEL and a monolayer of intimal cells. Lp(a) localization was examined histologically by using a mouse monoclonal anti-Lp(a) antibody. Lp(a), found in all injured arteries, was localized primarily in the neointima in 50% of the vessels. In the subset of vessels with evidence of thrombus formation, intense Lp(a) immunostaining was associated with the thrombus. Lp(a) was specific to injured arteries as uninjured vessels did not stain. In addition, staining was not seen with a negative control, a nonspecific mouse IgG1 antibody. The presence of Lp(a) at the site of rapid neointimal growth supports a role for this lipoprotein in the response to vascular injury after balloon angioplasty.     

The use of relational databases in the transition from quality assurance to continuous quality improvement: a clinical practice model

BACKGROUND AND OBJECTIVE: The solid-state, mid-infrared holmium:YAG laser (2.1 microm wavelength) is a relatively new percutaneous device that has recently been evaluated in a multicenter study. Because of its unique wavelength and photoacoustic effects on atherosclerotic plaques, this laser may be useful in treatment of symptomatic patients with coronary artery disease. This study sought to evaluate the safety and efficacy of mid-infrared laser angioplasty in the treatment of coronary artery lesions. PATIENTS AND METHODS: Laser angioplasty was performed on 2,038 atherosclerotic lesions in 1,862 consecutive patients with a mean age of 61 +/- 11 years. Clinical indications included unstable angina (69%), stable angina (20%), acute infarction (6%), and positive exercise test (5%). Complex lesion morphology included eccentricity (62%), thrombus (30%), total occlusion (27%), long lesions (14%), and saphenous vein grafts (11%). RESULTS: This laser catheter alone successfully reduced stenosis (>20%) in 87% of lesions. With adjunct balloon angioplasty, 93% procedural success was achieved. The presence of thrombus within the target lesion was a predictor of procedural success (OR = 2.0 [95% confidence interval 2.0, 4.0], P = .04). Bifurcation lesions (OR = 0.5 [95% confidence interval 0.2, 1.0], P = .05) and severe tortuosity of the treated vessel (OR = 0.4 [95% confidence interval 0.2, 0.9], P = .02) were identified as significant predictors of decreased laser success. Calcium within the lesion was associated with reduced procedural success (OR = 0.57 [95% confidence interval 0.34, 0.97], P = .03), and calcified lesions required significantly more energy pulses than noncalcified lesions (119 +/- 91 pulses vs. 101 +/- 86 pulses, respectively, P = .0002). Complications included in-hospital bypass surgery 2.5%, Q-wave myocardial infarction 1.2%, and death 0.8%. Perforation occurred in 2.2% of patients; major dissection in 5.8% of patients, and spasm in 12% of patients. No predictor of major complications was identified. Six-month angiographic restenosis was documented in 54% of patients, and clinical restenosis occurred in 34% of patients. CONCLUSION: Mid-infrared laser has a safety profile similar to that of other debulking devices. This laser may be useful in select patients presenting with acute ischemic syndromes associated with intracoronary thrombus; however, like other coronary lasers, it is limited by the need for adjunctive balloon angioplasty and/or stenting to achieve adequate final luminal diameter. No beneficial effects on reducing 6-month restenosis rates were observed.     

Coronary stenosis progression differs in patients with stable angina pectoris with and without a previous history of unstable angina

OBJECTIVES: To compare the evolution of stenoses responsible for acute coronary events with those not associated with acute coronary syndromes. METHODS AND RESULTS: We prospectively studied angiographic stenosis progression in 190 stable angina patients, with single vessel disease, who were awaiting non-urgent coronary angioplasty. Sixty four patients had a previous history of unstable angina (Group 1) and 126 patients had no history of unstable angina (Group 2). Culprit stenoses were classified as "complex' or "smooth'. At restudy, 8 +/- 4 months after the first angiogram, 12 of 63 culprit stenoses in Group 1 had progressed and seven of 125 in Group 2 (19% vs 6%, P = 0.0044). Thirteen of 68 complex culprit stenoses had progressed, compared with only 6 of 120 smooth culprit stenoses (19% vs 5%, P = 0.003). Coronary events occurred in 12 Group 1 patients and nine Group 2 patients (P = 0.02). CONCLUSIONS: In patients with stable angina, stenoses associated with previous episodes of unstable angina are more likely to progress than stenoses not associated with previous unstable angina. Unstable coronary atherosclerotic plaques, even those that have been clinically stable for more than 3 months, may retain the potential for rapid progression to total occlusion.     

Enhanced inflammatory response to coronary angioplasty in patients with severe unstable angina

BACKGROUND: Systemic markers of inflammation have been found in unstable angina. Disruption of culprit coronary stenoses may cause a greater inflammatory response in patients with unstable than those with stable angina. We assessed the time course of C-reactive protein (CRP), serum amyloid A protein (SAA), and interleukin-6 (IL-6) after single-vessel PTCA in 30 patients with stable and 56 patients with unstable angina (protocol A). We also studied 12 patients with stable and 15 with unstable angina after diagnostic coronary angiography (protocol B). METHODS AND RESULTS: Peripheral blood samples were taken before and 6, 24, 48, and 72 hours after PTCA or angiography. In protocol A, baseline CRP, SAA, and IL-6 levels were normal in 87% of stable and 29% of unstable patients. After PTCA, CRP, SAA, and IL-6 did not change in stable patients and unstable patients with normal baseline levels but increased in unstable patients with raised baseline levels (all P<0.001). In protocol B, CRP, SAA, and IL-6 did not change in stable angina patients after angiography but increased in unstable angina patients (all P<0.05). Baseline CRP and SAA levels correlated with their peak values after PTCA and angiography (all P<0.001). CONCLUSIONS: Our data suggest that plaque rupture per se is not the main cause of the acute-phase protein increase in unstable angina and that increased baseline levels of acute-phase proteins are a marker of the hyperresponsiveness of the inflammatory system even to small stimuli. Thus, an enhanced inflammatory response to nonspecific stimuli may be involved in the pathogenesis of unstable angina.     

Does low individual operator coronary interventional procedural volume correlate with worse institutional procedural outcome?

OBJECTIVES: To assess the relation between individual operator coronary interventional volume and incidence of complications, the in-hospital outcome at a single, moderate volume urban academic center was prospectively collected over a 3-year period. BACKGROUND: A minimum of 75 coronary interventions/operator per year may be required in the future to obtain formal certification. However, few data exist regarding individual operator volumes and procedural outcome. METHODS: Between January 1993 and December 1995, 1,389 consecutive procedures were performed or supervised by nine geographic full-time operators: 171 (12.3%) utilized various devices, and 350 (25.2%) involved multivessel coronary intervention. Left ventricular ejection fraction was 59 +/- 15% (mean +/- SD), and there were 1.7 +/- 0.7 vessels diseased (with > or = 70% stenosis). Clinical indications included stable angina in 22.5% of cases, unstable angina in 31.9%, acute myocardial infarction (MI) in 2.9%, post MI in 20.6%, shock or acute heart failure in 3.0% and restenosis in 19.1%. In the last consecutive 857 lesions in 655 cases, 20.7% type A, 55.5% type B and 23.8% type C lesions were categorized before coronary intervention. RESULTS: Average yearly operator volume ranged from 26 to 83 cases (mean 51 +/- 26). Each operator has performed a total of 590 +/- 268 coronary interventions, with 10.0 +/- 4.3 years of coronary interventional experience. The mean angioplasty volume rating for the nine operators was 180 +/- 37 (> 170 considered adequate). The in-hospital major complication rate was 1.4% (95% confidence interval 0.7% to 1.893%) for all coronary interventions, including death in 3 patients, bypass surgery in 13, arrhythmia in 3 and Q wave MI in 2. To ascertain how these outcomes compared with standard measures of coronary interventional outcome, four previously published registries were reanalyzed in a similar manner. The rate of complications in the present study was found to be significantly lower than that of the 1992-1993 Society for Cardiac Angiography and Intervention registry (1.9%, n = 19,594, p < 0.05 [excludes ventricular arrhythmias]), the 1994 American College of Cardiology database (3.9%, n = 38,963, p = 0.001), the Mid-America Heart Institute outcome in 1988 (2.3%, n = 5,413, p = 0.02) and the 1985-1986 National Heart, Lung, and Blood Institute Registry (7.2%, n = 1,801, p = 0.001). Odds ratios and 95% confidence intervals showed the outcome in the current study to be at least comparable to the standard registries. CONCLUSIONS: Despite individual operator volumes below those currently being considered for credentialing, the overall institutional outcome was excellent in a diverse and complex patient population.     

Are directional coronary atherectomy and Palmaz-Schatz stent more efficacious than conventional balloon angioplasty for treating de novo coronary artery lesions?

It is unclear whether new devices such as directional coronary atherectomy (DCA) or Palmaz-Schatz stent implantation improve long-term outcomes compared with conventional balloon angioplasty in patients with stable angina and de novo coronary artery lesions of type A or type B except for complete occlusive lesions investigated by the American College of Cardiology/American Heart Association task force on percutaneous transluminal coronary angioplasty. A total of 146 patients with stable angina and simple lesions were assigned to either conventional balloon angioplasty (62 patients), DCA (50 patients), or Palmaz-Schatz implantation (34 patients). The acute results and late outcomes were assessed by coronary angiography. The results of the three procedures were similar with respect to procedural success and complications. Patients who underwent stenting or DCA had a larger immediate increase in the diameter of the lumen and a larger luminal diameter immediately after the procedure than those who underwent balloon angioplasty. At six months follow-up, the patients treated by stenting continued to have a larger luminal diameter and a lower rate of restenosis than those treated with balloon angioplasty (2.30 +/- 0.66 vs 1.85 +/- 0.83 mm, p < 0.005; 5.9% vs 29%, p < 0.05) and DCA (2.30 +/- 0.66 vs 1.90 +/- 0.96 mm, p < 0.05; 5.9% vs 24%, NS). The patients treated with balloon angioplasty had a smaller late loss than those treated with DCA or Palmaz-Schatz stent. The patients treated with DCA had a larger loss index than those treated with balloon angioplasty or Palmaz-Schatz stent. Stenting was a significant factor in decreasing the rate of restenosis by logistic regression analysis, compared with balloon angioplasty. The angiographic outcomes were better in patients who received a stent than in those who received other treatments. This study suggests that even lesions stable for treatment by balloon angioplasty and DCA can also be treated with Palmaz-Schatz stents.     

Angioscopic predictors of early adverse outcome after coronary angioplasty in patients with unstable angina and non-Q-wave myocardial infarction

BACKGROUND: Clinical and angiographic criteria have a limited ability to predict adverse outcome in patients with unstable angina who are undergoing percutaneous transluminal coronary angioplasty (PTCA). We investigated whether the use of angioscopy can improve prediction of early adverse outcome after PTCA. METHODS AND RESULTS: Angioscopic characterization of the culprit lesion was performed before PTCA in 32 patients with unstable angina and 10 with non-Q-wave infarction. Seven patients (17%) had an adverse outcome (myocardial infarction, repeat PTCA, or need for coronary artery bypass graft surgery) within 24 hours after PTCA. Six of 18 patients with a yellow culprit lesion had an adverse outcome compared with 1 of 24 in whom the culprit lesion was white (P = .03). Six of 20 patients with plaque disruption suffered an adverse outcome compared with 1 of 22 with nondisrupted plaques (P = .04). Six of 17 patients with intraluminal thrombus had an adverse outcome, whereas only 1 of 25 patients without thrombus suffered an adverse outcome (P = .01). Yellow color, disruption, and thrombus at the culprit lesion site were associated with an eightfold increase in risk of adverse outcome after PTCA. The prediction of PTCA outcome based on characteristics of the plaque that were identifiable by angioscopy was superior to that estimated by the use of angiographic variables. CONCLUSIONS: In patients with unstable angina and non-Q-wave infarction, angioscopic features of disruption, yellow color, or thrombus at the culprit lesion site can identify patients at high risk of early adverse outcome after PTCA. Angioscopy was superior to angiography for prediction of PTCA outcome.     

Tissue-factor antigen and activity in human coronary atherosclerotic plaques

BACKGROUND: Coronary atherosclerotic-plaque thrombosis is a key event in the pathogenesis of unstable angina and myocardial infarction. Although plaque rupture or fissuring frequently occurs in atherosclerosis, only a small proportion of ruptured plaques develop thromboses. METHODS: Tissue-factor antigen and activity were measured in atherectomy samples from 50 consecutive patients with coronary artery disease (stable angina n = 19, unstable angina n = 24, and myocardial infarction n = 7). FINDINGS: Median tissue-factor antigen and activity concentrations were significantly higher in plaques from patients with unstable angina and myocardial infarction than in those from patients with stable angina (antigen: 66.1 pg/mg [interquartile range 43.8-82.5] vs 32.4 pg/mg [9.8-43.4], p = 0.0001; activity: 0.22 mU/mg [0.17-0.41] vs 0.13 mU/mg [0.05-0.16], p = 0.0004). INTERPRETATION: Tissue-factor, an initiator of the coagulation cascade, may account for the different thrombotic responses to the rupture of human coronary atherosclerotic plaques.     

Lipoprotein(a) and inflammation in human coronary atheroma: association with the severity of clinical presentation

OBJECTIVES: The purpose of this study was the investigation of the in vivo role of lipoprotein(a) [Lp(a)] and inflammatory infiltrates in the human coronary atherosclerotic plaque and their correlation with the clinical syndrome of presentation. BACKGROUND: Lipoprotein(a) is an atherogenic and thrombogenic lipoprotein, and has been implicated in the pathogenesis of acute coronary syndromes. Lipoprotein(a) induces monocyte chemoattraction and smooth muscle cell activation in vitro. Macrophage infiltration is considered one of the mechanisms of plaque rupture. METHODS: This study of atherectomy specimens investigated the in vivo role of Lp(a) at different stages of the atherogenic process, and its relationship with macrophage infiltration. We examined coronary atheroma removed from 72 patients with stable or unstable angina. Specimens were stained with antibodies specific for Lp(a), macrophages (KP-1), and smooth muscle cells (alpha-actin). Morphometric analysis was used to quantify the plaque areas occupied by each of the three antigens, and their colocalization. RESULTS: All specimens had localized Lp(a) staining; the mean fractional area was 58.2%. Ninety percent of the macrophage areas colocalized with Lp(a) positive areas, whereas 31.3% of the smooth muscle cell areas colocalized with Lp(a) positive areas. Patients with unstable angina (n = 46) had specimens with larger mean plaque Lp(a) areas than specimens from stable angina patients (n = 26): 64.4% versus 47.7% (p = 0.004). Unstable angina patients with rest pain (n = 28) had greater mean plaque Lp(a) area than unstable angina patients with crescendo exertional pain (n = 18): 71.1% versus 52.4% (p < 0.001). Mean KP-1 area was 31.2% in unstable rest angina versus 18.3% in stable angina (p = 0.05); alpha-actin area was greater in stable (48.5%) and crescendo exertional angina (48.8%) than in rest angina (30.4%). The strongest correlation between plaque KP-1 and Lp(a) area was in unstable rest angina (r = 0.88, p < 0.001), and between alpha-actin and Lp(a) areas in the crescendo exertional angina (r = 0.62, p < 0.01). CONCLUSIONS: Lipoprotein(a) is ubiquitous in human coronary atheroma. It is detected in larger amounts in tissue from culprit lesions in patients with unstable compared to stable syndromes, and has significant colocalization with plaque macrophages. A correlation of plaque alpha-actin and Lp(a) area suggests a role of Lp(a) in plaque growth.     

Treatment of ostial lesions of the left anterior descending coronary artery with Palmaz-Schatz coronary stent

We evaluated acute and long-term clinical and angiographic results of elective Palmaz-Schatz coronary stent implantation for left anterior descending coronary artery (LAD) ostial stenosis in 23 consecutive patients. Eight patients had stable angina, 14 had unstable angina, and 1 had recent myocardial infarction. Sixteen patients had single-vessel, 5 had double-vessel, and 2 had triple-vessel disease. Clinical success without major complications (death, acute myocardial infarction, emergency coronary artery bypass grafting) was obtained in all cases and technical success in 20 cases (86.9%). After stenting, minimal lumen diameter increased from 1.05 +/- 0.45 mm to 2.89 +/- 0.52 mm (p < 0.001), and percent diameter stenosis decreased from 65.49% +/- 13.36% to 2.94% +/- 19.93% (p < 0.001). One case of subacute thrombosis and no major bleeding occurred. Twenty patients were followed-up for 6 months, during which no acute cardiac event (death, acute myocardial infarction) was observed. Eighteen patients were eligible for follow-up coronary angiography; restenosis (> or = 50% diameter stenosis) was observed in 4 (22.2%). Minimal lumen diameter was 1.77 +/- 0.55 mm, percent diameter stenosis was 39.66% +/- 17.62%, late loss was 1.01 +/- 0.69 mm, net gain was 0.79 +/- 0.55 mm, and loss index (late loss/acute gain) was 0.53 +/- 0.37. This study suggests that elective Palmaz-Schatz stent implantation may be a safe and successful treatment of LAD ostial lesions and provides a large increase in lumen diameter.     

The use of empiric clinical data in the evaluation of practice guidelines for unstable angina

OBJECTIVE: To determine the applicability to emergency department (ED) clinical practice of a nationally disseminated practice guideline on the disposition of patients with a diagnosis of unstable angina, and to determine the potential impact of the guideline on hospital admissions and demand for intensive care beds. DESIGN: Application of guideline criteria for ED disposition decisions to a validation sample derived from a prospective clinical trial. SETTING: Five hospitals, including 2 urban general teaching hospitals, 2 urban tertiary care university hospitals, and 1 suburban university-affiliated community hospital. PATIENTS: A consecutive sample of 457 patients who presented with symptoms suggestive of acute cardiac ischemia and who had "unstable angina" or "rule out unstable angina" diagnosed by ED physicians. Greater than 90% of eligible patients were enrolled in the clinical trial; follow-up data sufficient for assignment of a definitive diagnosis were obtained for 99% of subjects. MAIN OUTCOME MEASURES: Acute myocardial infarction and unstable angina, based on blind review of initial and follow-up clinical data, including cardiac enzyme levels and electrocardiograms. After completion of the trial, without knowledge of final diagnosis or outcome, the investigators classified patients into risk groups specified by the unstable angina guideline. RESULTS: Of subjects with an ED diagnosis of unstable angina, only 6% (n=28) met the guideline's criteria corresponding to low risk for adverse events and were therefore suitable for discharge directly to home. Fifty-four percent (n=247) met the intermediate-risk criteria; 40% (n=182) met the high-risk criteria and were identified as requiring admission to an intensive care unit. Actual ED disposition differed from guideline recommendations in 2 major areas: only 4% (1/28) of low-risk patients were discharged to home with outpatient follow-up, and only 40% (72/182) of high-risk patients were admitted to an intensive care unit. CONCLUSIONS: Although the guideline was intended to reduce hospitalization by identifying a low-risk group, the small size of this group among ED patients suggests that little reduction in hospitalization can be expected. Indeed, the guideline may increase demand for the limited number of intensive care beds to accommodate patients with unstable angina considered high-risk but currently placed elsewhere. These results emphasize the need to use empiric data from target clinical settings to assess the likely actual impact of guidelines on clinical care prior to national dissemination.     

Thrombosis in ischemic heart disease

Thrombus formation on a fissured or disrupted atherosclerotic plaque is the main pathogenetic mechanism for the acute coronary syndromes of myocardial infarction and unstable angina. Myocardial infarction results from an acute total occlusion of the artery, while unstable angina is secondary in most cases to mural thrombus formation. Thrombus formation has also been implicated in chronic atherosclerotic disease progression and in restenosis following coronary angioplasty. Therapeutic measures to treat thrombus rely on the ability of drugs to either prevent thrombus extension, dissolve its fibrin component, or prevent further platelet aggregation. Other measures rely on the ability of intracoronary techniques to open coronary arteries. The primary prevention of intracoronary thrombus formation is evolving. Measures to stabilize plaques or to reduce hypercoagulability are being tested or have been tested in recent trials.     

Long-term effect of alkaline, organic acid, or hot water washes on the microbial profile of refrigerated beef contaminated with bacterial pathogens after washing

One hundred consecutive patients (81 male and 19 female) with unstable angina pectoris undergoing coronary angiography were divided according to Braunwald's clinical classification. Seventeen (17%) patients had new onset angina (class I), 68 (68%) sub-acute angina (class II) and 15 (15%) had acute rest angina (class III). Twenty-seven (27%) patients had secondary unstable angina pectoris (class A), 49 (49%) primary unstable angina (class B) and 24 (24%) had post-infarction unstable angina (class C). ST-T wave changes on ECG were present in 54 (54%) while absent in 46 (46%) patients. On coronary angiography, 26 (26%) patients had single vessel disease, 30 (30%) double vessel disease and 39 (39%) patients had triple vessel disease. Five (5%) patients were found to have normal coronaries. Classification of patients according to Braunwald's clinical classification showed single vessel disease to be higher in class I as compared to class II (47% vs 22%; p = 0.04) and classes III (47% vs 20%; p<0.01). Single vessel disease was found to be higher in class C as compared to class B (41.7% vs 16.4; p = 0.01). Double vessel disease was higher in class B as compared to class A (40.8% vs 18.5%, p = 0.04). Triple vessel disease incidence was not found to be significantly different among different clinical classes. Morphology of coronary artery lesions was classified according to Ambrose's classification. Out of the total of 248 lesions in the whole study group, there were 68 (27.42%) concentric lesions, 55 (22.18%) eccentric type I lesions, 23 (9.27%) eccentric type II lesions, 42 (16.94%) multiple irregularity lesions and 60 (24.19%) totally occluded lesions. Concentric lesions were found to be higher in class C as compared to class B (40% vs 19.8%; p = 0.014). Statistically significant difference was not present in the distribution of other morphological type of lesions among different clinical classes. In the whole study group, intra-luminal thrombus was found to be present in 17 (17%) of patients. Distribution of intra-luminal thrombus according to Braunwald's classification showed that none of the patients in class I had intra-luminal thrombus, while 13 (19.1%) patients in class II and 4(26.7%) in class III had intra-luminal thrombus. The difference in the occurrence of intra-luminal thrombus between class I and class II (p = 0.004) and class I and class III (p = 0 .03 was found to be significant. Thus, majority of patients undergoing coronary angiography had primary sub-acute rest angina. Single vessel disease was higher in new onset angina. Patients with unstable angina pectoris and ST-T changes on ECG had higher number of lesions per patient and higher eccentric type I lesions. Intra-luminal thrombus was more frequently encountered with acute rest angina. However, the distribution of different morphological type of lesions on coronary angiography did not differ significantly in different clinical classes of unstable angina pectoris divided according to Braunwald's classification.     

Increased apoptosis and necrosis of coronary plaques in unstable angina

In acute coronary syndromes, arteriosclerotic plaques are characterized by inflammation and decreased smooth muscle cell density. The underlying pathogenic processes remain unclear. Among others, increased programmed cell death (apoptosis) is postulated. Coronary atherectomy specimens from 26 patients with unstable angina (group 1) and from 24 patients with stable angina (group 2) were examined, using immunohistochemistry (TUNEL test to detect fragmented DNA) and transmission electron microscopy. The objectives of the present study were to evaluate plaque group differences in the cellular composition, to detect and quantify cell death, and to differentiate between apoptosis and necrosis. Group 1 lesions contained more macrophages and lymphocytes as well as significantly (p = 0.01) less smooth muscle cells compared with group 2 lesions, whereas both revealed a comparable cell density. All plaques showed signals for fragmented DNA. TUNEL-positive cells were seen more frequently in lesions with unstable angina (p = 0.04). Ultrastructural analysis revealed signs of programmed cell death, such as nuclear alterations, cellular condensation due to lost adhesion, and apoptotic bodies. Importantly, group I lesions comprised significantly more apoptotic SMCs and apoptotic macrophages compared with group 2 lesions (28% vs. 16%; p = 0.02). Also, cellular necroses were found to be increased in lesions with unstable angina (18% vs. 8%; p = 0.02). The density of macrophages showed a positive correlation to the incidence of cellular necroses in group 1 lesions (r = 0.44; p = 0.02), but not in group 2 lesions. In both plaque groups, this determinant was independent from cellular apoptosis, also at high levels as found with unstable angina. The present study on coronary atherectomy specimens with unstable angina reveals intimal macrophage infiltration and the density of apoptotic as well as necrotic intimal cells to be increased, whereas the content of intact SMCs was reduced. Increased, macrophage-independent apoptosis strongly points to the presence of one or several pro-apoptotic intimal factor(s) predisposing to plaque rupture. Implications of our findings may be directed to identify this (these) factor(s) and to modulate endogenous apoptotic activity with the ultimate goal to raise regional smooth muscle cell density.