Dysfunctional endothelial nitric oxide biosynthesis in healthy smokers with impaired endothelium-dependent vasodilatation.

BACKGROUND: The mechanisms involved in the dysfunction of both endothelium-dependent vasodilatation (EDV) and NO biosynthesis related to smoking are unclear. In this study, EDV was assessed in healthy smokers and nonsmokers in vivo and, using serum from the same individuals, was related to the NO biosynthetic pathway in vitro. METHODS AND RESULTS: Flow-mediated EDV of the brachial artery was measured in 23 male patients (8 nonsmokers and 15 smokers). Serum was collected, added to confluent ( approximately 85%) monolayers of human umbilical vein endothelial cells (HUVECs), and incubated for 12 hours. Basal and substance P-stimulated NO production was measured. The HUVECs used for measuring basal NO production were lysed, and both endothelial NO synthase (eNOS) protein expression and eNOS activity were determined. EDV was lower in smokers compared with nonsmokers (P<0.001). HUVECs treated with serum from smokers compared with nonsmokers showed significantly lower basal (P<0.0001) and stimulated (P<0.02) NO production, higher eNOS expression (P<0.0001), but lower eNOS activity (P<0.004). There was a significant positive correlation between in vivo EDV and in vitro substance P-stimulated NO production (rho=0.57, P<0.01) and between basal NO production and eNOS activity (r=0.54, P<0.008) and a negative correlation between basal NO production and eNOS protein expression (r=-0.60, P<0.003). CONCLUIONS: This is the first study to combine an in vivo model with a near-physiological in vitro model to demonstrate an association between decreased NO production and reduced EDV. Cigarette smoking was associated with reduced EDV, NO generation, and eNOS activity in the presence of increased eNOS protein expression.

Plaque disruption and the acute coronary syndromes of unstable angina and myocardial infarction: if the substrate is similar, why is the clinical presentation different?

In a majority of instances, both unstable angina and acute myocardial infarction occur secondary to plaque disruption and thrombus formation. Although the pathogenetic substrates are similar the clinical presentations are quite different. It is hypothesized in this editorial review that the amount of acute thrombus formation and specifically fibrin deposition is greater in myocardial infarction than in unstable angina. Both angiographic studies and studies analyzing the response to thrombolytic agents suggest more thrombus in myocardial infarction than in unstable angina. These data have recently been substantiated by angioscopic observations in these acute syndromes suggesting that more platelet-rich (whitish) thrombus occurs in unstable angina and more red thrombus in myocardial infarction. The red thrombus presumably would be more responsive to thrombolytic agents. Furthermore, it is proposed that these differences between syndromes in acute thrombus formation can be explained by the interplay of vessel wall injury, coagulation variables or stasis of blood flow occurring at or after the time of presentation. Therefore, acute myocardial infarction is associated with occlusive, fibrin-rich thrombus, whereas in unstable angina, the thrombus is nonocclusive, mural and possibly more platelet-rich. However, the clinical syndrome that ultimately develops after plaque disruption is dependent not only on the amount of acute thrombus formation but on the net result of all factors that influence the balance between coronary blood supply and myocardial oxygen demand.

Isolated chronic mitral regurgitation with preserved systolic left ventricular function and severe pulmonary hypertension.

Pulmonary hypertension in chronic mitral valve disease has been related most commonly to left ventricular dysfunction or mitral stenosis; its association with chronic, isolated mitral regurgitation and preserved left ventricular systolic function is unclear. In 41 catheterized patients with chronic mitral regurgitation (known history of mitral regurgitation for greater than 18 months) and preserved left ventricular systolic function (ejection fraction greater than 0.55), historic, electrocardiographic, echocardiographic and hemodynamic variables were analyzed. Ten patients (Group I) had normal pulmonary artery systolic pressure (less than 30 mm Hg), whereas 31 patients had pulmonary hypertension. Pulmonary artery systolic pressure was mildly increased (30 to 49 mm Hg) in 13 patients (Group II) and was greater than or equal to 50 mm Hg in 18 patients (Group III). Univariate analysis showed the more frequent occurrence of male gender and ruptured chordae tendineae in the groups with pulmonary hypertension. Mean pulmonary capillary wedge pressure, size of the V wave in pulmonary capillary wedge pressure and pulmonary arteriole resistance were higher, whereas cardiac index was lower in the hypertension groups. Multivariate stepwise analysis revealed higher mean pulmonary capillary wedge pressure and pulmonary arteriole resistance as the only variables independently differing among groups. In conclusion, pulmonary hypertension occurs frequently (76% of cases) in patients with chronic, isolated mitral regurgitation with preserved left ventricular systolic function. In these patients, a severe increase in pulmonary capillary wedge pressure is associated with elevation in pulmonary artery resistance, a finding similar to that in mitral stenosis.

Morphologic and dynamic changes of atherosclerotic plaque at the carotid artery bifurcation: sequential imaging by real time B-mode ultrasonography.

Occurrence of new symptoms of focal cerebrovascular disease, including completed cerebral infarction, transient cerebral ischemic attack and amaurosis fugax, was correlated with changes in size and morphology of atherosclerotic plaques at the carotid artery bifurcation visualized by real time B-mode ultrasonography. Bilateral serial images of 246 plaques in 123 patients were made in a time interval of 9 to 35 months between initial and follow-up studies. There was a significantly higher incidence of symptoms ipsilateral to plaques that grew [30 (25%) of 121] than of symptoms ipsilateral to plaques that diminished or remained unchanged [8 (8%) of 98] (p less than 0.001). Plaques that became hemodynamically obstructive by causing disruption of laminar flow or reduction of distal perfusion pressure at the ophthalmic artery were associated with a higher frequency of symptoms [12 (40%) of 30] than were nonobstructive plaques [26 (13%) of 201] (p less than 0.001). There was also a strong association between symptoms and plaque configuration. Mural plaques growing in a crescentic configuration along the wall of the carotid bifurcation between the first and second examination had a higher incidence of symptoms [22 (40%) of 56] than did plaques that grew but maintained a nodular configuration [8 (12%) of 65] (p less than 0.001), although the same proportion of each became hemodynamically obstructive. Sequential visualization of atherosclerotic plaques by real time B-mode ultrasonography of the carotid bifurcation may provide a method for studying the pathogenesis of arterial thrombosis.

Angiographic morphology and the pathogenesis of unstable angina pectoris.

In 110 patients with either stable or unstable angina, the morphology of coronary artery lesions was qualitatively assessed at angiography. Each obstruction reducing the luminal diameter of the vessel by 50% or greater was categorized into one of the following morphologic groups: concentric (symmetric narrowing); type I eccentric (asymmetric narrowing with smooth borders and a broad neck); type II eccentric (asymmetric with a narrow neck or irregular borders, or both); and multiple irregular coronary narrowings in series. For the entire group, type II eccentric lesions were significantly more frequent in the 63 patients with unstable angina (p less than 0.001), whereas concentric and type I eccentric lesions were seen more frequently in the 47 patients with stable angina (p less than 0.05). Type II eccentric lesions were also present in 29 of 41 arteries in patients with unstable angina compared with 4 of 25 arteries in those with stable angina (p less than 0.0001) in whom an "angina-producing" artery could be identified. Therefore, type II eccentric lesions are frequent in patients with unstable angina and probably represent ruptured atherosclerotic plaques or partially occlusive thrombi, or both. A temporary decrease in coronary perfusion secondary to these plaques with or without superimposed transient platelet thrombi or altered vasomotor tone may be responsible for chest pain in some of these patients with unstable angina.

Left ventricular function after myocardial infarction: clinical and angiographic correlations.

There is a paucity of information correlating the angiographic findings immediately after myocardial infarction with the clinical status before infarction. Therefore, the coronary anatomy, collateral circulation and quantitative left ventricular function were studied in 39 patients who underwent angiography within 3 weeks of a first transmural myocardial infarction. In all patients, the vessel supplying the infarct was totally occluded at the time of angiography. Patients without angina before infarction (Group I) had fewer coronary obstructions than did patients with a long history of angina before infarction (Group II) (1.5 +/- 0.5 versus 2.5 +/- 0.5, respectively, p less than 0.001) but worse overall and regional left ventricular function. These paradoxical differences between Groups I and II were evident in patients with anterior as well as inferior infarction. Patients in Group I had significantly lower collateral scores than did patients in Group II (0.6 +/- 0.8 versus 1.9 +/- 0.9, respectively, p less than 0.0001) and 13 of 22 patients in Group I had no collateral vessels compared with only 1 of 17 in Group II (p less than 0.001). Partial preservation of anterior wall function in Group II patients with anterior infarction was related both to the presence of collateral vessels and to the more distal obstruction of the left anterior descending coronary artery in these patients as compared with patients with anterior infarction in Group I. In contrast, in patients with inferior wall infarction, no relation could be found between the presence of collateral vessels and regional left ventricular function, although only two patients in this series with inferior infarction did not have collateral vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombosis-related markers in unstable angina pectoris.

While thrombus formation has been implicated in the pathogenesis of unstable angina, the value of thrombus-related markers for distinguishing unstable from stable angina is not well defined. Fibrin D-dimer and plasminogen activator inhibitor were prospectively analyzed in the peripheral blood of 46 patients (26 with unstable angina and 20 with stable angina or normal coronary arteries). Baseline blood samples were drawn within 24 h after rest pain in patients with unstable angina and in 19 of these 26 patients in less than 6 h. In patients with unstable angina, mean +/- SD (median) values for fibrin D-dimer and plasminogen activator inhibitor values measured 0.09 +/- 0.06 (0.07) microgram/ml and 9.1 +/- 9.6 (5.9) IU, respectively, compared to 0.11 +/- 0.10 (0.05) microgram/ml and 5.5 +/- 1.9 (5.0) IU/ml, in patients in the control group (p = NS for all comparisons between the two groups). Recurrent in-hospital pain, coronary anatomy and need for intervention showed no relation to the levels of these markers. In 19 additional patients (9 with unstable angina and 10 control patients) samples from the coronary sinus and the peripheral blood were also analyzed. Again, in patients with unstable angina all samples were drawn less than 24 h after rest pain; in six of nine patients samples were drawn in less than 6 h. A coronary sinus to peripheral blood gradient for either of these markers could not be demonstrated. The differences between peripheral and coronary sinus D-dimer and plasminogen activator inhibitor concentrations were also similar in patients with unstable angina and control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of angiographic morphology and clinical presentation in unstable angina.

OBJECTIVES: This study sought to correlate angiographically detected complex lesions and intracoronary thrombus with the severity of clinical presentation in unstable angina (UA). BACKGROUND: Unstable angina is usually related to acute thrombosis superimposed on a disrupted plaque. Complex and thrombotic lesions are more prevalent in UA and have been associated with a worse prognosis. The highest levels of the Braunwald classification of UA (III = rest angina within 48 h of presentation; C = postinfarction angina; and c = angina refractory to maximal medical therapy) can be used to assess the severity of clinical presentation, but they have not been directly correlated with thrombotic and complex lesions. METHODS: We conducted a prospective study of 284 patients with UA who underwent cardiac catheterization. A single angiographer with no knowledge of the clinical classifications interpreted all angiograms. Culprit lesions identified in 200 patients were classified as simple or complex. Complex lesions included the categories complex morphology, intracoronary thrombus (ICT) or total occlusion. Lesions were also quantitatively analyzed, and Thrombolysis in Myocardial Infarction (TIMI) flow was assessed. Univariate and multivariate logistic regression analyses of the angiographic findings were performed controlling for all cardiac risk factors, previous angioplasty or bypass surgery and multivessel disease, and we sequentially compared Braunwald classes III, C and c with classes < III, < C and < c, respectively. RESULTS: Class III was associated with complex lesions (p = 0.04) and decreased TIMI flow (p = 0.03). Class C angina correlated with complex lesions (p = 0.04), ICT (p = 0.005) and decreased TIMI flow (p = 0.03). Class c angina was associated with ICT (p = 0.02). The degree of stenosis by quantitative angiography was not associated with any particular Braunwald class. CONCLUSIONS: Recent rest pain and refractory or postinfarction UA, or both, are strongly associated with the general category of complex lesions and specifically with angiographically detected ICT and decreased TIMI flow.

A prolonged QRS duration on surface electrocardiogram is a specific indicator of left ventricular dysfunction [see comment].

OBJECTIVE: We sought to determine whether a prolonged QRS-interval duration is associated with decreased left ventricular (LV) systolic function. BACKGROUND: The 12-lead electrocardiogram (ECG) is a routine test for suspected cardiac disease. Although several scoring systems have been devised to estimate LV systolic function, no studies have examined the direct relationship between QRS duration alone and LV systolic function. METHODS: We analyzed the standard 12-lead surface ECG of 270 consecutive patients, referred for radionuclide ventriculography. Patients (n = 44) with bundle branch blocks, atrial flutter or fibrillation, pacemaker rhythm, recent myocardial infarction or bypass surgery, and patients on antiarrhythmic drugs were excluded. In the remaining patients (n = 226), we correlated the QRS duration on standard resting ECG, and the resting LV ejection fraction (EF), end-systolic and end-diastolic counts (ESC and EDC, respectively; LV volume indices), as obtained by radionuclide angiography. We used a multivariate analysis to identify independent predictors of reduced ventricular function entering QRS duration, the previously described R-wave score and clinical variables in our model. RESULTS: The QRS duration in the abnormal EF group was significantly longer than in the normal EF group (0.102 vs. 0.091 s, p < 0.0001). A QRS duration >0.10 s was highly specific (83.6%), but modestly sensitive (43.8%), for the prediction of abnormal EF. Furthermore, an abnormal EF was predicted with incrementally increased specificity (83.6% to 99.3%) and a corresponding decrease in sensitivity (43.8% to 13.8%) for each 0.01-s increase in the definition of prolonged QRS (from >0.10 to >0.12 s). Accordingly, the positive likelihood ratio for the prediction of decreased LV function was increased from 2.67 to 19.7 as the definition of prolonged QRS duration was increased from >0.10 to >0.12 s. In the multivariate analysis, a prolonged QRS duration and a low R-wave score were the only independent predictors of decreased LV systolic function. CONCLUSIONS: Prolonged QRS duration (>0.10 s) obtained from a standard resting 12-lead ECG is a specific, but relatively insensitive indicator of decreased LV systolic function. Further prolongation of the QRS had a higher specificity for decreased LV EF and a higher positive likelihood ratio for predicting abnormal LV EF.

Quantitative and qualitative effects of intracoronary streptokinase in unstable angina and non-Q wave infarction.

Thrombolytic therapy has been shown to be effective in reopening totally occluded arteries in acute myocardial infarction. Coronary thrombus is also believed to play a role in the pathophysiology of unstable angina and non-Q wave infarction. However, few patients with these two acute coronary syndromes have been treated with intracoronary streptokinase. Therefore, 100,000 to 300,000 IU (mean 177,000 +/- 80,000 IU) of intracoronary streptokinase was infused into 36 consecutive catheterized patients who either presented with an acute episode of unstable angina or had had a recent non-Q wave infarction and in whom a less than 100% occluded ischemia-producing artery could be identified. Qualitative techniques utilizing vessel magnification and quantitative analysis with digital subtraction were performed on the ischemia-producing coronary lesion before and immediately after streptokinase therapy and 3 to 10 days later in 18 patients who were restudied at the time of transluminal coronary angioplasty. Before streptokinase treatment, 24 (67%) of 36 ischemia-producing arteries contained eccentric, irregular lesions. The percent diameter stenosis and percent area stenosis in all ischemia-producing arteries averaged 83.8 +/- 8.3% and 94.8 +/- 3.3%, respectively. After streptokinase treatment there were 23 arteries (64%) with eccentric irregular lesions. The percent diameter stenosis and percent area stenosis in all ischemia-producing arteries were similar to pre-streptokinase values (82.9 +/- 5.9% and 93.8 +/- 4.0%, respectively). At restudy, there were also no significant changes in any quantitative or qualitative variable. Five individual patients showed a significant reduction in percent stenosis after streptokinase. This improvement was independent of duration of symptoms, use of heparin before angiography, streptokinase dose or reduction of fibrinogen levels post-streptokinase. Two additional patients deteriorated clinically and developed total occlusion of the ischemia-producing artery within 12 hours of streptokinase infusion. These data suggest that intracoronary streptokinase may be of limited utility in either unstable angina or recent non-Q wave infarction with a less than 100% occluded ischemia-producing artery. In these syndromes, thrombus may be organized or short infusions may be given too late to be effective. In some cases, thrombus may even be absent. Whether longer infusion of streptokinase or other thrombolytic agents will be of benefit remains to be determined.

Comparison of single plane videodensitometry-based right ventricular ejection fraction in right and left anterior oblique views to biplane geometry-based right ventricular ejection fraction.

To evaluate the reliability of the videodensitometric assessment of right ventricular ejection fraction, 38 patients were studied during diagnostic cardiac catheterization. Digital subtraction images of the right ventricle were obtained in both the right anterior oblique and the left anterior oblique views, using direct intraventricular injection of dilute contrast medium. From the end-diastolic and end-systolic images obtained in each view, analysis of the relative brightness values generated a videodensitometry-based right ventricular ejection fraction for both the right and the left anterior oblique views. These values were compared with those generated by applying the geometry-based Simpson's rule to the orthogonal images. Right ventricular ejection fraction ranged from 22 to 88%. Videodensitometric ejection fraction in the right anterior oblique view correlated well with that in the left anterior oblique view (r = 0.88) and each correlated well with geometry-based ejection fraction (r = 0.91 and 0.82, respectively). In a subset of 18 patients without significant cardiac disease, mean videodensitometric right ventricular ejection fraction was 68% (versus 61% in the abnormal subset), and it correlated closely with left ventricular ejection fraction (r = 0.82). Videodensitometric analysis of digital subtraction images provides a reliable method for calculating right ventricular ejection fraction that is independent of geometry and reliably separates normal from abnormal values. Application of videodensitometric techniques should simplify analysis of the response of the right ventricle to different interventions in patients with cardiac disease.

Effect of nitroglycerin during hemodynamic estimation of valve orifice in patients with mitral stenosis.

In patients with mitral stenosis, valve orifice calculations using pulmonary capillary wedge pressure as a substitute for left atrial pressure may overestimate the severity of disease. Previous studies have shown that mitral valve area determined from transseptal left atrial pressure measurements exceeds that area derived from pulmonary wedge pressure measurements. This is probably due to pulmonary venoconstriction, which is reversed by nitroglycerin. Nitroglycerin, 0.4 mg, was administered sublingually to 20 patients with mitral valve disease during preoperative cardiac catheterization using the pulmonary capillary wedge pressure as the proximal hydraulic variable. At the time of a peak hypotensive effect, 3 to 5 minutes after nitroglycerin administration, the mean pulmonary capillary wedge pressure decreased from 23 +/- 2 (mean +/- SEM) to 19 +/- 2 mm Hg (p less than 0.005). The mean diastolic transmitral pressure gradient (12.6 +/- 1.2 mm Hg before and 11.5 +/- 1.0 mm Hg after nitroglycerin; p = NS) and cardiac output (4.0 +/- 0.3 to 4.1 +/- 0.3 liters/min; p = NS) did not change significantly. Nevertheless, the hemodynamic mitral orifice area, calculated using the Gorlin formula, increased from 0.8 +/- 0.1 to 1.1 +/- 0.2 cm2 (p less than 0.05). In 12 patients with isolated mitral stenosis, without regurgitation, the mitral valve orifice area after nitroglycerin was 0.4 +/- 0.2 cm2 larger than it was before drug administration (p less than 0.05). Administration of nitroglycerin during evaluation of mitral stenosis eliminates pulmonary venoconstriction, which raises the pulmonary capillary wedge pressure above the left atrial pressure in some patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiographic evolution of coronary artery morphology in unstable angina.

As previously reported in acute presentations of unstable angina, an identifiable characteristic coronary artery lesion has been found in about 70% of cases at coronary arteriography. This takes the form of an eccentrically placed convex stenosis with a narrow neck due to one or more overhanging edges or irregular, scalloped borders, or both. To study the evolution of lesions responsible for unstable angina, coronary artery anatomy and morphology on angiography were evaluated in patients with stable angina progressing to unstable angina. Group I comprised 25 patients with a history of stable angina who were restudied after an acute episode of unstable angina and Group II comprised 21 patients with little or no change in symptoms between catheterizations. Progression of coronary disease occurred in 19 (76%) of 25 patients in Group I compared with 7 (33%) of 21 in Group II (p less than 0.001). Of the 25 lesions with progression in Group I, 17 progressed to less than 100% and 8 to 100% occlusion. Eighteen of these 25 lesions in Group I were previously insignificant (less than 50% occlusion on the first catheterization). In contrast, of the eight lesions with disease progression in Group II, only two were previously insignificant while six showed at least 50% occlusion on the initial study. The eccentric lesion was seen in 71% of all lesions with progression to less than 100% occlusion in Group I, but it was not seen in any Group II vessel with progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiographic progression of coronary artery disease and the development of myocardial infarction.

There are few data on angiographic coronary artery anatomy in patients whose coronary artery disease progresses to myocardial infarction. In this retrospective analysis, progression of coronary artery disease between two cardiac catheterization procedures is described in 38 patients: 23 patients (Group I) who had a myocardial infarction between the two studies and 15 patients (Group II) who presented with one or more new total occlusions at the second study without sustaining an intervening infarction. In Group I the median percent stenosis on the initial angiogram of the artery related to the infarct at restudy was significantly less than the median percent stenosis of lesions that subsequently were the site of a new total occlusion in Group II (48 versus 73.5%, p less than 0.05). In the infarct-related artery in Group I, only 5 (22%) of 23 lesions were initially greater than 70%, whereas in Group II, 11 (61%) of 18 lesions that progressed to total occlusion were initially greater than 70% (p less than 0.01). In Group I, patients who developed a Q wave infarction had less severe narrowing at initial angiography in the subsequent infarct-related artery (34%) than did patients who developed a non-Q wave infarction (80%) (p less than 0.05). Univariate and multivariate analysis of angiographic and clinical characteristics present at initial angiography in Group I revealed proximal lesion location as the only significant predictor of evolution of lesions greater than or equal to 50% to infarction. This retrospective study suggests that myocardial infarction frequently develops from previously nonsevere lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of nitroglycerin on the pulmonary venous gradient in patients after mitral valve replacement.

Because the equality of the pulmonary artery wedge pressure and left atrial pressure has been questioned in patients with mitral valve disease and pulmonary hypertension, this study examined how vasomotor activity in the pulmonary capacitance vessels might contribute to a discrepancy between these pressures. The difference between the pulmonary wedge and left atrial pressures (designated as the pulmonary venous gradient) was measured after nitroglycerin administration in nine patients who had pulmonary hypertension (mean pulmonary artery pressure 40 mm Hg) after mitral valve replacement. Five minutes after sublingual nitroglycerin, 0.4 mg, the mean pulmonary wedge pressure decreased from 19 +/- 2 to 13 +/- 2 mm Hg (p less than 0.005), exceeding the decrease in left atrial pressure (15 +/- 2 to 11 +/- 2 mm Hg; p less than 0.005). Pulmonary blood flow increased from 4.6 +/- 0.4 to 4.9 +/- 0.4 liters/min (p less than 0.005). The decrease in mean pulmonary venous gradient from 4.0 +/- 0.8 to 1.7 +/- 0.6 mm Hg (p less than 0.025) was attributed to nitrate-mediated pulmonary venodilation. The ratio of venous gradient to blood flow, an index of pulmonary venous tone, decreased after nitroglycerin from 0.9 +/- 0.2 to 0.4 +/- 0.1 (p less than 0.01). These data indicate that reversible pulmonary vasoconstriction contributes to elevation of the pulmonary wedge pressure above the left atrial pressure in patients with chronic mitral valve disease and pulmonary hypertension and that nitroglycerin may produce pulmonary venodilation decreasing the pulmonary venous gradient.

Coronary angiographic morphology in myocardial infarction: a link between the pathogenesis of unstable angina and myocardial infarction.

It has previously been shown that analysis of coronary morphology can separate unstable from stable angina. An eccentric stenosis with a narrow neck or irregular borders, or both, is very common in patients who present with acute unstable angina, whereas it is rare in patients with stable angina. To extend these observations to myocardial infarction, the coronary morphology of 41 patients with acute or recent infarction and nontotally occluded infarct vessels was studied. For all patients, 27 (66%) of 41 infarct vessels contained this eccentric narrowing, whereas only 2 (11%) of 18 noninfarct vessels with narrowing of 50 to less than 100% had this lesion (p less than 0.001). In addition, a separate group of patients with acute myocardial infarction who underwent intracoronary streptokinase infusion were also analyzed in similar fashion. Fourteen (61%) of 23 infarct vessels contained this lesion after streptokinase infusion compared with 1 (9%) of 11 noninfarct vessels with narrowing of 50 to less than 100% (p less than 0.01). Therefore, an eccentric coronary stenosis with a narrow neck or irregular borders, or both, is the most common morphologic feature on angiography in both acute and recent infarction as well as unstable angina. This lesion probably represents either a disrupted atherosclerotic plaque or a partially occlusive or lysed thrombus, or both. The predominance of this morphology in both unstable angina and acute infarction suggests a possible link between these two conditions. Unstable angina and myocardial infarction may form a continuous spectrum with the clinical outcome dependent on the subsequent change in coronary supply relative to myocardial demand.

Adjunctive thrombolytic therapy for angioplasty in ischemic rest angina: results of a double-blind randomized pilot study.

OBJECTIVES: A multicenter pilot study was instituted to assess the role of intracoronary thrombolytic therapy during angioplasty for ischemic rest angina. BACKGROUND: Acute thrombotic coronary occlusion is increased during angioplasty for unstable angina, and intracoronary thrombolytic agents have been used to maintain patency. Prophylactic use of intracoronary thrombolytic agents has been advocated in certain high risk subgroups, although no studies have randomized therapy. METHODS: Ninety-three patients with either unstable angina and pain at rest (trial A, 66 patients) or postinfarction pain at rest (trial B, 27 patients) were randomized in double-blind fashion to administration of either intracoronary urokinase, 150,000 U, or saline solution placebo given immediately before angioplasty. Cineangiograms of the culprit lesion were recorded and analyzed in blinded fashion by a core laboratory for definite or possible (haziness) filling defects 15 min after angioplasty or after acute closure. RESULTS: Urokinase decreased filling defects at 15 min after angioplasty in comparison with placebo (14% vs. 29%, respectively, p = 0.08). Four patients in each treatment group developed acute vessel closure. However, although urokinase significantly reduced the incidence of filling defects in trial A (3% vs. 23%, p = 0.03), the drug had no effect at the selected dose in trial B (42% vs. 43%, respectively). Acute vessel closure occurred significantly more frequently in trial B than in trial A, and urokinase at the selected dose also had no effect. Ischemic events after angioplasty appeared to be related more to dissection than to thrombosis, although redilation, which was more frequent after placebo administration, may have reduced their incidence as well as that of acute closure. CONCLUSIONS: These data suggest a possible role for intracoronary urokinase during angioplasty for unstable angina. The lack of effect after infarction may represent a greater thrombus burden or degree of plaque disruption. A trial utilizing higher doses of urokinase in a larger patient group is in progress.

Percutaneous balloon mitral valvuloplasty in comparison with open mitral valve commissurotomy for mitral stenosis during pregnancy.

OBJECTIVES: We sought to compare the maternal and fetal outcomes of patients with severe mitral stenosis submitted to percutaneous balloon dilation versus open mitral valve commissurotomy (MVC) during pregnancy. BACKGROUND: Heart failure in patients with mitral stenosis complicating pregnancy is a common problem in developing countries. Since 1984, percutaneous dilation of the mitral valve using a balloon catheter has become a therapeutic alternative to open heart surgery. Although the efficacy of percutaneous mitral valve balloon dilation is well established, its results have never before been compared with the results of commissurotomy during pregnancy. METHODS: We compared the clinical and obstetric complications in 45 women who were treated with percutaneous mitral valve balloon dilation (group I, n = 21; from 1990 to 1995) or open MVC (group II, n = 24; from 1985 to 1990) for severe heart failure due to mitral stenosis during pregnancy. RESULTS: In our study, percutaneous balloon dilation of the mitral valve had a success rate of 95% (Gorlin formula) and 90.5% (echocardiographic "pressure half-time" method), as demonstrated by the final mitral valve area achieved. This improvement was followed by a marked decrease in the mitral valve gradient, left atrial pressure and mean pulmonary artery pressure. Patients in both groups had similar improvements in symptoms. Patients who underwent percutaneous balloon dilation had significantly fewer fetal complications, with a reduction in fetal and neonatal mortality (1 death in group I vs. 8 in group II, p = 0.025). CONCLUSIONS: Percutaneous balloon mitral valvuloplasty is safe and effective and appears to be preferable for the fetus, compared with open MVC during pregnancy.

Angiographic patterns of balloon inflation during percutaneous transluminal coronary angioplasty: role of pressure-diameter curves in studying distensibility and elasticity of the stenotic lesion and the mechanism of dilation.

There are few in vivo data concerning the mechanisms of balloon inflation during coronary angioplasty. To characterize how lesions dilate, videodensitometry was used to measure the diameter of the inflated balloon across 29 coronary lesions in 27 patients. Pressure-diameter curves for each lesion were derived with use of a standardized incremental inflation protocol in which pressures between 2 and 6 atm in 3 mm low profile balloons approximated normal vessel diameter. The diameter of coronary stenosis before and after angioplasty was also measured. Pressure-diameter curves showed that the most improvement in luminal caliber occurred at low inflation pressure. A distensibility factor was defined as the ratio of the amount of balloon inflation at 2 atm compared with the balloon diameter at 6 atm. Eccentric irregular lesions (n = 11) had a greater distensibility factor (0.49 +/- 0.17) than did lesions (n = 18) without this configuration (0.33 +/- 0.14) (p less than 0.02). The former were soft, presumably because of thrombus in these lesions. In addition, there were no differences in patterns of balloon inflation for lesions requiring additional inflation or for dilations resulting in an intimal crack or dissection after angioplasty. There was often a loss of luminal caliber when balloon diameter at 6 atm was compared with the diameter after angioplasty. This was defined as elasticity or recoil. There was a significant direct correlation between the amount of elasticity and the extent of balloon inflation at 6 atm (that is, lesions more fully dilated at 6 atm showed more elasticity).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty of complex lesions in ischemic rest angina: results of the Thrombolysis and Angioplasty in Unstable Angina (TAUSA) trial.

OBJECTIVES: This study sought to analyze the role of complex lesion morphology on the acute results of angioplasty. BACKGROUND: Acute complications of angioplasty are higher in unstable than in stable angina. The unstable culprit lesion is usually complex, indicative of plaque disruption and thrombus formation. Previous nonrandomized studies have shown that the presence of intracoronary thombus increases morbidity after coronary angioplasty. The role of complex morphology in coronary angioplasty outcome was studied in a prespecified subgroup analysis of a large multicenter coronary angioplasty trial. METHODS: The results of coronary angioplasty from the Thrombolysis and Angioplasty in Unstable Angina (TAUSA) trial were analyzed. This large trial randomized 469 patients in double-blinded manner to receive either intracoronary urokinase or placebo during coronary angioplasty of the culprit lesion in ischemic rest angina with or without recent infarction. The study presented here analyzes in detail the results of coronary angioplasty in complex versus simple lesions in the urokinase and placebo groups. Complex lesions were defined before angioplasty by a core laboratory as having one or more of the following: irregular borders, overhanging edges, ulcerations or intraluminal filling defects proximal or distal to the lesion. RESULTS: Of the 469 patients, 458 had identifiable culprit lesions, of which 245 were complex and 213 were simple. Complex lesions were associated with a higher abrupt closure rate than simple lesions (10.6% vs. 3.3%, respectively, p < 0.003). Patients with complex lesions also had higher recurrent in-hospital angina (p < 0.02) and emergent bypass surgery (p < 0.02). Further analysis of complex lesions revealed that abrupt closure was particularly high in the urokinase group (15.0% vs 5.9% for the placebo group, p < 0.03), and most abrupt closures were thrombotic. Composite clinical end points were also significantly higher with complex lesions and urokinase. In the placebo group, complex lesions had a higher abrupt closure rate as well as postcoronary angioplasty filling defects, but clinical end points were not significantly different. CONCLUSIONS: Complex lesions before coronary angioplasty increase acute complication rates after coronary angioplasty. Urokinase as administered in the TAUSA trial had significant adverse effects, especially in complex lesions. However, even in the placebo arm, complex lesions were associated with higher complication rates than simple lesions. Newer antithrombotic measures that particularly target the platelet may eventually decrease complication rates in these lesions.