Diseased Coronary Segments Research Articles

Coronary anatomy predicts presence or absence of renal artery stenosis. A prospective study in patients undergoing cardiac catheterization for suspected coronary artery disease

Aims This study aimed to determine the prevalence of renal artery stenosis (RAS) and associated risk factors in patients undergoing cardiac catheterization for suspected coronary artery disease (CAD). Methods One hundred and seventy-seven consecutive patients (62 females) with a serum creatinine concentration <2·0mg.dl−1 were studied. Abdominal aortography followed cardiac catheterization to screen for RAS. Results In 110 patients (62%) CAD and in 19 patients (11%) significant RAS (luminal narrowing of ≥50%) were detected, 12 of whom had high grade (≥70%) RAS, and two subjects had significant RAS without CAD. Patients with RAS were older (67±8 vs 61±11 years, mean±SD;P =0·004), had higher systolic blood pressure (150±15 vs 138±20mmHg;P =0·005), a lower glomerular filtration rate (GFR; 61±16 vs 80±22ml.min−1, P<0·001) and more often diabetes mellitus (69% vs 30%; P=0·004). In multivariate analysis a low GFR and the extent of CAD were independent predictors of RAS. The presence of >2 significant coronary lesions predicted RAS (sensitivity 0·84, specificity 0·77, positive predictive value 0·30, negative predictive value 0·98). Conclusion Screening for RAS in patients with >2 diseased coronary segments has a high diagnostic yield, which is even greater in the presence of a reduced GFR, diabetes mellitus, and elevated systolic blood pressure.Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved .

Remodeling pattern within diseased coronary segments as evidenced by intravascular ultrasound

Remodeling pattern within diseased coronary segments as evidenced by intravascular ultrasound

What constitutes optimal surgical revascularization?: Answers from the bypass angioplasty revascularization investigation (BARI)

ObjectivesThe study was done to derive the optimum definition of complete revascularization in coronary artery bypass surgery. Background“Complete revascularization” has been considered the goal of coronary artery bypass operations, but various definitions of completeness exist. MethodsWe evaluated the Bypass Angioplasty Revascularization Investigation (BARI) surgical results in the seven years after operation. Different definitions of completeness of revascularization were retrospectively applied to the 1,507 patients in the combined randomized/registry group to derive the definition of complete operative revascularization with the best discrimination in long-term results between those with and without complete revascularization as defined. Four definitions were evaluated: 1) traditional complete revascularization with one graft to each major diseased artery system; 2) functional complete revascularization with one graft to all diseased major or primary segmental vessels; 3) number of distal anastomoses greater than, equal to or less than the number of diseased coronary segments; and 4) number of distal anastomoses to the major coronary systems equal to 1 or greater than 1. ResultsNo independent survival advantage existed for traditional or functional complete revascularization as compared with incomplete revascularization. No survival advantage existed for any of the three arms of definition 3. For definition 4, seven-year death/myocardial infarction was highest (32.9%) when more than one anastomosis was constructed to any non-left anterior descending coronary artery (LAD) system (relative risk 1.37, p = 0.03). No increased risk was associated with constructing more than one anastomosis into the LAD system. ConclusionsThe construction of more than one graft to any system other than the LAD appears to confer no long-term advantage, and may actually be deleterious.

Elective stenting of "unprotected" left main coronary stenosis in patients without contraindication to bypass surgery

Coronary surgery is at this point of time the standard therapy of unprotected left main coronary artery stenosis. Coronary angioplasty (PTCA) is performed only in bail out situations. The number of publications of successful percutaneous intervention in unprotected left main coronary stenosis is increasing because of increasing use of stents and ticlopidine to avoid stent-thrombosis. From 9/96 to 7/98, 13 patients with unprotected left main coronary stenosis were treated with stents. All of them were accepted by the heart surgeon for bypass surgery but were not considered to be optimal candidates due to advanced age of more than 80 years (n = 5), significant co-morbidity (n = 2) or diffuse diseased peripheral coronary segments (n = 6). Mean age of patients was 74 +/- 10 years, 9 were male, and all patients presented with angina III-IV (CCS). Mean ejection fraction was 55 +/- 15%. Localization of stenoses were classified as ostial (n = 5), middle (n = 3), and bifurcational (n = 6). One patient had stenoses both in the ostium and in the bifurcation. In all cases a PTCA of the culprit stenosis was performed prior to stent implantation. The mean diameter of the stents used was 3.3 +/- 0.3 mm and the mean length was 11 +/- 4 mm. In 6 patients a PTCA of either left anterior descendens (LAD) or right coronary artery was performed in the same session. In 4 of these patients it was followed by a stent implantation. All procedures were performed with surgical stand-by, an intraaortal balloon pump was available, but was not uses prophylactically. Stent implantation could be performed successfully in 12 out of the 13 patients (success rate 92%). In bifurcational stenoses stents were positioned with the proximal end in the left main and the distal end in the LAD. Significant injury or occlusion of the circumflex artery was not observed. In one patient with bifurcational stenosis with severe calcification it was not possible to cross the lesion with an accurate sized balloon. Trying to cross with a smaller balloon (2.5 mm) resulted in dissection of the left main coronary artery which could not be reopened again by catheter technique. This patient was transferred to the operating room under conditions of cardiopulmonary resuscitation and a bypass surgery was performed. He was dismissed from the hospital with no evidence of perioperative myocardial infarction. The mean time for follow-up was 12 +/- 7 months, all patients are still alive. In 6 patients an angiography was performed during follow-up because of suspicion of recurrent ischemia. Two patients out of these 6 had restenoses in the left main coronary artery which were re-dilated (17%). Another 2 patients had stenoses in other coronary segments and were also dilated. Thus, stenting of left main coronary artery stenoses is feasible, however, with acceptable risks and could be considered in selected patients as an alternative to coronary artery surgery.

Long-term follow-up study of coronary reconstruction with multiple stents

Background Conventional balloon angioplasty of very long de novo coronary lesions or very long coronary dissection caused by angioplasty is associated with low success and high complication rates. Multiple intracoronary stents have been used to treat both conditions, although long-term efficacy has not been defined. Methods and Results Between June 1993 and December 1995, 47 consecutive patients underwent native coronary angioplasty and stenting with 4 or more stents covering at least 2 consecutive diseased coronary segments. Preangioplasty and poststenting diameter stenoses were 81% ± 13% and 21% ± 12%, respectively. Reference vessel diameters were 3.53 ± 0.55 mm proximal to the stents and 2.95 ± 0.62 mm distal to the stents. Average lesion length was 63 ± 20 mm. The number of stents used was 4.5 ± 1 per vessel (from 4 to 7). Gianturco Roubin I stents were used in all patients. Coronary Palmaz-Schatz stents were used as supplementary stents in 3 patients. Angiographic success was 100%. In-hospital outcomes include 1 death, 1 coronary bypass surgery, no Q-wave myocardial infarction, and 7 non–Q-wave myocardial infarctions. Long-term follow-up at 430 ± 199 days was completed in all patients. Thirty-five (76%) patients were asymptomatic, 8 (17%) had class 1 or 2 angina, 1 had a myocardial infarction, 13 (28%) underwent repeat angioplasty, 2 patients had subsequent elective bypass surgery, and 3 died during follow-up. Conclusions Multiple intracoronary stents for very long lesions or dissection can be performed with acceptable immediate and long-term outcomes. (Am Heart J 1999;137:292-7.)

Bradykinin-mediated cardiovascular protective actions of ACE inhibitors. A new dimension in anti-ischaemic therapy?

In addition to being accepted therapy in hypertension and heart failure, ACE inhibitors may well offer a new dimension in anti-ischaemic therapy. Currently, anti-ischaemic properties have been demonstrated by ACE inhibitors in selected patient groups, including patients with left ventricular dysfunction with or without a direct temporal relationship with myocardial infarction. Anti-ischaemic effects of ACE inhibitors become apparent late after initiation of treatment and suggest a structural rather than a functional effect. Underlying mechanisms may include a reduction in ventricular dilatation and (abnormal) cardiac hypertrophy, leading to less myocardial oxygen demand and, possibly, improved subendocardial blood supply, and vasculoprotective effects, i.e. anti-atherosclerotic and antiremodelling properties, a beneficial effect on the fibrinolytic system and an improvement in abnormal endothelial vasodilator function. The latter aspect is most probably the pivotal mode of action where the anti-ischaemic profile of ACE inhibition is concerned. An improvement in endothelial dysfunction has been shown in patients with mild to moderate coronary artery disease [Trial on Reversing ENdothelial Dysfunction (TREND)]. It is of importance that, in both clinical experiments and human studies, the role of bradykinin appears central in the structural and functional cardiovascular effects of ACE inhibition. This is particularly true for the improvement of impaired endothelial function. Myocardial ischaemia evokes vasoconstrictor neurohormonal activation, which may lead to coronary vasoconstriction in diseased coronary segments. The subsequent abnormal endothelial function leads to diminished coronary flow and also increases systemic vasotone and afterload, thus unfavourably altering the myocardial oxygen supply/demand ratio. Under laboratory conditions, acute ACE inhibition counteracts this activation in humans. However, it is speculated that this anti-ischaemic mechanism may become operative and clinically important during long term oral ACE inhibitor therapy when endothelial function improves, and may subsequently protect against the vasoconstrictor effect of neurohormonal activation. As it is unlikely that the mechanisms mentioned above are only relevant in patients with ventricular dysfunction or heart failure, several large controlled trials are currently examining the long term anti-ischaemic and cardiovascular protective effects of ACE inhibition in patients at risk of a cardiovascular event [Heart Outcomes Prevention Evaluation study (HOPE)], with a normal cardiac function [Prevention of Events with ACE inhibition study (PEACE)] or in all patients with coronary artery disease irrespective of cardiac function [EUropean trial of Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA)].

Effects of the Intracoronary Infusion of Cocaine on Coronary Arterial Dimensions and Blood Flow in Humans

This study was done to assess the influence of large concentrations of cocaine (infused into the left coronary artery) on coronary arterial dimensions and blood flow in humans. In 20 subjects undergoing cardiac catheterization, incrementally increasing doses of (1) saline solution (n = 10, controls) or (2) cocaine hydrochloride (n = 10) were infused into the left coronary artery, and the effects on heart rate, systemic arterial pressure, coronary sinus blood flow, and coronary arterial dimensions were measured. Saline solution induced no change in any variable. With the infusion of cocaine, there was an incremental increase in its concentration in the systemic (femoral arterial) and coronary (coronary sinus) circulations (maximal concentrations, 0.14 ± 0.06 [mean ± SD] and 3.50 ± 0.70 mg/L, respectively). At the maximal cocaine infusion rate, heart rate and diastolic arterial pressure increased slightly, but coronary sinus blood flow and the dimensions of nondiseased and diseased coronary arterial segments did not change. Thus, intracoronary infusion of cocaine in an amount sufficient to achieve a high concentration in the coronary circulation does not induce epicardial coronary arterial vasoconstriction or alter blood flow. (Am J Cardiol 1996;78:288–291)

775-5 Increased Incidence of Chlamydia Bacteria Detected within Coronary Arteries of Patients with Atherosclerotic Versus Transplant Induced Coronary Artery Disease

Previous work has suggested an association between Chlamydia pneumoniae infection and coronary atherosclerosis, based on the demonstration of increased serologic titers and the detection of bacteria within atherosclerotic tissue. We sought to strengthen a possible etiologic link by comparing the incidence of Chlamydia infection in coronary atherosclerotic tissue to that in coronary arteries of patients with non-atherosclerotic cardiovascular disease. Coronary tissue specimens obtained from 90 consecutive patients (mean age = 57 yrs) with symptomatic coronary artery disease undergoing directional coronary atherectomy were tested for the presence of Chlamydia species by direct immunofluorescence using mouse monoclonal antibody. Immunofluorescence was positive in 68 (76%), equivocal in 5 (6%) and negative in 19 (21 %) of specimens. Polymerase chain reaction confirmed the specific Chlamydia strain TWAR in 2 cases. No clinical factors except the presence of a primary non-testenotic lesion (odds ratio = 3.0, p = 0.057) predicted the detection of Chlamydia. As a control, coronary tissue specimens from 11 patients with previous cardiac transplantation and subsequent transplant-induced coronary artery disease were also tested. Direct immunofluorescence performed on these diseased coronary artery segments was negative for Chlamydia in every case (p = 0.0001 compared with atherosclerotic specimens). This high incidence of Chlamydia detected only in coronary arteries diseased by atherosclerosis suggests an etiologic role for Chlamydia infection in the development of coronary atherosclerosis, which should be further studied.

995-19 The Impact of Mental Stress and α-Adrenergic Activation on the Microcirculation of Patients with Coronary Artery Disease

Mental stress results in sympathetic activation and provokes constriction of diseased epicardial coronary artery segments, which may decrease coronary blood flow. We investigated the effect of mental stress (10 min. video game) on the coronary microcirculation by measuring cardiac norepinephrine spillover (NESP) and left anterior descending (LAD) coronary artery blood flow (intracoronary Doppler flow velocity and quantitative angiography) in non-significantly diseased (&lt;40% stenosis) LAD arteries of 7 patients with significant coronary artery disease (CAD; &gt; 50% stenosis) of other vessels. These responses were compared to those in 5 patients with normal coronary angiograms (NCA). Coronary vascular resistance (CVR) was calculated by dividing mean blood pressure (MBP) by coronary blood flow. Measurements during mental stress were compared to pre-mental stress measurements. Data = mean ± S.D. during mental stress.%Change in:MBPNESPLAD diameterCVRNCA+ 13 ± 8+ 123 ± 130+ 4 ± 10–26 ± 9CAD+ 19 ± 10+ 90 ± 64+ 1 ± 6–4 ± 18**p &lt; 0.05 vs NCA p &lt; 0.05 vs NCA Mental stress resulted in significant coronary microvascular dilation in patients with NCA (p &lt; 0.05 vs pre-mental stress) in contrast to no vasodilation in patients with CAD (p = NS). 5 CAD patients underwent repeat mental stress (MS), following intracoronary phentolamine (P) 0.02 mg/kg.%Change in:MSPNESPLAD diameterCVRControl MS+ 26 ± 13+ 87 ± 40+ 1 ± 6–9 ± 14P + MS+ 18 ± 9+ 254 ± 117**+ 3 ± 7**–28 ± 19****p &lt; 0.01 vs Control MS p &lt; 0.01 vs Control MS Even though phentolamine increased NESP substantially due to presynaptic α2;-adrenergic blockade, microvascular dilation was greater during repeat mental stress in CAD patients than during their initial mental stress, and similar in magnitude to the response of NCA patients. Thus, coronary atherosclerosis is associated with absence of a microvascular vasodilator response to mental stress, due to α-adrenergic constrictor effects on the coronary microcirculation.

Balloon angioplasty results in increased segmental coronary distensibiliy: A likely mechanism of percutaneous transluminal coronary angioplasty

Objectives. The purpose of this study was to evaluate the hypothesis that the increase in lumen area induced by percutaneous transluminal coronary angioplasty is secondary to a change in lesion (segmental) distensibility.Background. Despite the widespread use of coronary angioplasty, the precise mechanism (or mechanisms) of lumen area improvement remains poorly understood.Methods. Quantitative coronary angiography was used to measure the minimal (contrast agent filled) balloon diameters at 1 to 5 atm, inclusive, during the first and final balloon inflations in 24 lesions successfully treated with coronary angioplasty. To rule out possible confounding effects due to changes in balloon material distensibility during repeated inflations, five control balloons were studied ex vivo. In parallel, intravascular ultrasound imaging was utilized to compare the segmental distensibility (change in lumen area during the cardiac cycle) of eight disease-free and seven mildly diseased coronary segments and seven segments after successful balloon angioplasty.Results. Minimal balloon diameters increased significantly between the first and final inflations (46%, 33%, 26%, 14% and 10% at 1, 2, 3, 4 and 5 atm, respectively, all p < 0.0001), demonstrating an increase in arterial distensibility after successful coronary angioplasty. No significant changes in balloon diameters were observed during sequential initial inflations at 1 and 2 atm (n = 5). Minimal increases in Balloon diameters were observed during repeated balloon inflations in the ex vivo studies (4.9 ± 1% [mean ± SEM]). A distensibility index, derived from the intravascular ultrasound data, was not different between the balloon-dilated and the normal segments but was significantly lower in mildly diseased sites (14.7 ± 2.2 vs. 12.9 ± 1.2 vs. 6.9 ± 1.9, respectively, p < 0.05) despite a smaller plaque area (7.3 ± 1 vs. 11.3 ± 1 mm2, proximal/nondilated vs. dilated segments, respectively, p < 0.05).Conclusions. Coronary distensibility is significantly impaired in atherosclerotically diseased coronary segments and increases significantly after balloon angioplasty. This increase in segmental coronary compliance after coronary angioplasty may create a larger lumen area by allowing the vessel to distend in response to normal intraarterial pressure.

Determinants of coronary compliance in patients with coronary artery disease: An intravascular ultrasound study

Objectives. The aim of this study was to elucidate determinants of coronary compliance in patients with coronary artery disease.Background. Intravascular ultrasound potentially enables in vivo evaluation of coronary artery compliance.Methods. Twenty-seven patients (mean age [±SD] 57 ± 11 years, three women) undergoing coronary angioplasty were studied with intravascular ultrasound imaging. A mechanical intravascular ultrasound system (4.8F, 20 MHz) was used. A total of 58 dilferent coronary segments (proximal to the target angiographic lesion) were studied. Of these, 35 were located in the left anterior descending, 9 in the left main, 8 in the left circumflex and 6 in the right coronary arteries. During intravascular ultrasound imaging, 22 segments (38%) appeared normal, but 36 (62%) had plaque (24 fibrotic, 3 lipidic and 9 calcified). Systolic-diastolic changes in area (ΔA) and pressure (ΔP) with respect to vessel area (A) were used to study normalized compliance (Normalized compliance = [ΔA/AJ/ΔP [mm Hg−1×x 103]).Results. Lumen area and plaque area were 12.6 ± 5.7 and 3 ± 3 mm2, respectively. Plaque was concentric (more than two quadrants) at 10 sites, but the remaining 26 plaques were eccentric. Compliance was inversely related to age (r = −0.34, p < 0.05) but was not related to other clinical variables. Compliance was greater in the left main coronary artery (3.9 ± 2.1 vs. 1.8 ± 1.2 mm Hg−1, p < 0.05) and in coronary segments with normal findings on ultrasound imaging (2.9 ± 1.9 vs. 1.6 ± 1.1 mm Hg−1, p < 0.01). Moreover, at diseased coronary segments compliance was lower in calcified plaques than in other types of plaques (1.2 ± 9.7 vs. 2.3 ± 1.6 mm Hg−1, p < 0.01) but was similar in concentric and eccentric plaques (1.6 ± 1.5 vs. 1.6 ± 0.9 mm Hg−1). Plaque area (r = − 0.38, p < 0.01) was inversely correlated with compliance. On multivariate analysis, only age and plaque area were independently related to compliance.Conclusions. Intravascular ultrasound may be used to evaluate compliance in patients with coronary artery disease. Compliance is reduced with increasing age and is mainly determined by the arterial site and by the presence, size and characteristics of plaque on intravascular ultrasound imaging.

Coronary-artery vasoconstriction induced by cocaine, cigarette smoking, or both.

In humans, the use of cocaine and cigarette smoking each increase the heart's metabolic need for oxygen but may also decrease the supply of oxygen. As cocaine abuse has proliferated, cocaine-associated chest pain, myocardial infarction, and sudden death have occurred, especially among smokers. We assessed the influence of intranasal cocaine and cigarette smoking, alone and together, on myocardial oxygen demand and coronary arterial dimensions in subjects with and subjects without coronary atherosclerosis. In 42 smokers (28 men and 14 women; age, 34 to 79 years; 36 with angiographically demonstrable coronary artery disease), we measured the product of the heart rate and systolic arterial pressure (rate-pressure product) and coronary arterial diameters before and after intranasal cocaine at a dose of 2 mg per kilogram of body weight (n = 6), one cigarette (n = 12), or intranasal cocaine at a dose of 2 mg per kilogram followed by one cigarette (n = 24). No patient had chest pain or ischemic electrocardiographic changes after cocaine use or smoking. The mean (+/- SE) rate-pressure product increased by 11 +/- 2 percent after cocaine use (n = 30, P < 0.001), by 12 +/- 4 percent after one cigarette (n = 12, P = 0.021), and by 45 +/- 5 percent after both cocaine use and smoking (n = 24, P < 0.001). As compared with base-line measurements, the diameters of nondiseased coronary arterial segments decreased on average by 7 +/- 1 percent after cocaine use (P < 0.001), by 7 +/- 1 percent after smoking (P < 0.001), and by 6 +/- 2 percent after cocaine use and smoking (P < 0.001). The diameters of diseased segments decreased by 9 +/- 2 percent after cocaine use (n = 18, P < 0.001), by 5 +/- 5 percent after smoking (n = 12, P = 0.322), and by 19 +/- 4 percent after cocaine use and smoking (n = 12, P < 0.001). The increase in the rate-pressure product and the decrease in the diameters of diseased segments caused by cocaine use and smoking together were greater (P < 0.001 and P = 0.037, respectively) than the changes caused by either alone. The deleterious effects of cocaine on myocardial oxygen supply and demand are exacerbated by concomitant cigarette smoking. This combination substantially increases the metabolic requirement of the heart for oxygen but simultaneously decreases the diameter of diseased coronary arterial segments.

Predicting early and intermediate-term outcome of coronary angioplasty in the elderly.

Although the technical success rate of coronary angioplasty in the elderly in high, very old patients have increased risk of procedure-related death and late recurrence of severe angina. We proposed to determine baseline variables that predict early and intermediate-term failure of percutaneous transluminal coronary angioplasty (PTCA) in patients more than 65 so we could effectively stratify risk. We studied 982 patients at least 65 years old who had urgent or elective PTCA (1980 through 1990). Follow-up (mean, 25 months) was obtained for all patients. Multiple baseline variables were analyzed with univariate and multivariate logistic regression to select independent ones to fit predictive models for in-hospital death or myocardial infarction (overall rate, 6.3%), total in-hospital adverse outcome (overall rate, 18.7%), cumulative survival free of myocardial infarction (overall rate, 15% at 3 years), and cumulative survival free of late nonfatal myocardial infarction, bypass surgery, repeat PTCA, or recurrent severe angina (overall rate, 47% at 3 years). The most heavily weighted parameter in the probability regression equation for each end point was the number of diseased coronary artery segments with at least 70% stenosis. Advanced age was less important. The number of concomitant medical illnesses was predictive of late outcome but not early in-hospital events. Lowest risk quintile versus highest risk quintile event rate was 2.9% versus 14% for acute myocardial infarction or death and 17.2% versus 29% for cumulative in-hospital events. For posthospital events at 3 years' follow-up, lowest risk quintile death or myocardial infarction rate was 4% versus 33% for highest risk quintile. For cumulative late adverse events at 3 years, the event rate was 28% versus 63% for the highest risk quintile. These results stratify patients at high and low risk of early and intermediate-term success after PTCA and identify elderly patients in whom PTCA is most appropriate.

Three-dimensional MR imaging of the coronary arteries: preliminary clinical experience.

A three-dimensional (3D) magnetization-prepared (MP) rapid gradient-echo (RAGE) and 3D RAGE technique was used to image the coronary arteries in healthy volunteers and patients with known disease. Each sequence produced images of volumes partitioned into 16 thin sections with differing blood-fat-myocardium contrast. The two types of images were subtracted to null fat signal, thus producing a third image set that showed flowing blood. Total imaging time was about 17 minutes. In the volunteers, the 3D MP-RAGE and subtraction images consistently showed the morphology of the right coronary artery. The left main and left anterior descending arteries were also well seen. The circumflex artery was less consistently identified. Of the 17 diseased coronary artery segments identified at catheterization, 16 had altered signal intensity (narrowing, occlusion, reduced contrast-to-noise ratio, irregularity) on the subtraction images, while 13 had altered signal intensity on the 3D MP-RAGE images. The results indicate that this 3D MP-RAGE and 3D RAGE technique has potential utility as a screening method for coronary heart disease.

Effects of high-density lipoprotein on acetylcholine-induced coronary vasoreactivity

Recent evidence suggests that high-density lipoprotein (HDL) cholesterol has important vasoactive properties which may contribute to its beneficial effects on atherosclerotic coronary artery disease. The endothelium-dependent vasodilator acetylcholine has been used in a number of experimental studies to assess endothelial function. The relation between serum lipoproteins and acetylcholine-induced coronary vasoreactivity was investigated in patients (n = 27) undergoing elective coronary arteriography. Mean serum cholesterol, low-density lipoprotein cholesterol, HDL cholesterol and triglyceride levels were 189 ± 7 (4.84 ± 0.18 mmol/liter), 134 ± 6 (3.47 ± 0.15 mmol/liter), 41 ± 3 (1.06 ± 0.08 mmol/ liter) and 106 ± 30 mg/dl (1.20 ± 0.03 mmol/ liter), respectively. After a baseline arteriogram, acetylcholine was infused into the left main coronary artery and percent change from baseline dimension was determined in 27 angiographically smooth coronary artery segments and in 14 arterial segments with evidence of mild atherosclerotic disease. Intact vascular smooth muscle function was then confirmed in all segments by dilation to intracoronary nitroglycerin. Acetylcholine produced significant vasoconstriction of both angiographically smooth (13 ± 4%, p < 0.05 vs baseline) and diseased (19 ± 4%, p < 0.05 vs baseline) coronary segments. A positive correlation was observed between HDL cholesterol and normal acetylcholine-induced coronary vasoreactivity in both angiographically smooth (r = 0.59, p < 0.001) and diseased (r = 0.62, p < 0.02) coronary segments. No significant correlation was observed, however, between total and low-density lipoprotein cholesterol, or between total cholesterol to HDL ratio and the response of coronary artery diameter to acetylcholine infusion. These findings suggest that HDL cholesterol promotes normal endothelial cell function in both normal and atherosclerotic coronary segments. This beneficial effect may be related to a direct effect of HDL on release of endothelial-derived relaxing factor or may be secondary to its effects on endothelial cell proliferation. Thus, while HDL has important antiatherogenic properties, the clinical benefit of HDL elevation may be related, in part, to its effects on endothelial function and coronary vasoreactivity.

Effect of cocaine on coronary artery dimensions in atherosclerotic coronary artery disease: Enhanced vasoconstriction at sites of significant stenoses

Cocaine increases myocardial oxygen demand and paradoxically decreases oxygen supply by reducing coronary blood flow. Such “inappropriate” vasoconstriction also occurs with exercise, which causes intense vasoconstriction of coronary artery segments narrowed by atherosclerosis. This study was done to assess the cocaine-induced change in vasomotor tone of diseased and nondiseased coronary artery segments.In 18 patients (15 men, 3 women, aged 35 to 67 years), coronary artery areas in diseased and nondiseased segments were quantitated before and 15 min after administration of intranasal saline solution (6 patients) or cocaine (2 mg/kg body weight) (12 patients). No variables changed after intake of the saline solution. In response to cocaine, the luminal areas of diseased and nondiseased segments decreased, but the magnitude of vasoconstriction was greater in the diseased segments (mean ± SD 29 ± 23% versus 13 ± 8%, p < 0.05).Thus, cocaine causes vasoconstriction of diseased and nondiseased coronary artery segments, but its effect is particularly marked in the former.

Nitrate tolerance. A review of the evidence.

Organic nitrates are well established in the treatment of a wide variety of cardiovascular disorders, most notably angina pectoris and congestive heart failure. However, attenuation of, or tolerance to, haemodynamic and anti-ischaemic effects may occur with all long-acting nitrate formulations. In the majority of patients continuous administration of long acting nitrates tends to promote the development of attenuation, while intermittent administration avoids it. Likewise, higher-doses appear to induce attenuation to a greater degree than lower doses. Attenuation of haemodynamic effects and exercise tolerance in heart failure patients, and of clinical end-points in angina patients, appears to be less than attenuation of exercise testing end-points in angina patients. While the use of intermittent therapy avoids the development of attenuation, it may expose the patient to an as yet undefined risk of silent and/or symptomatic anginal episodes occurring during the nitrate-free interval. Likewise, the role of concomitant therapy in avoiding this potential risk remains to be defined. Means of avoiding attenuation may include the coadministration of sulfhydryl donors such as N-acetylcysteine. Alternatively, angiotension-converting enzyme (ACE) inhibitors such as captopril may block renin-angiotensin system-induced reflex sympathetic stimulation. Attenuation may occur to a greater or lesser degree in individual patients. The proportion of attenuators vs non-attenuators remains to be defined, as does a means of identifying such patients prospectively by clinical and/or laboratory parameters. Conflicting results among smaller studies may reflect variable proportions of attenuators vs non-attenuators. However, conflicting results among larger studies may reflect differences in patient selection criteria, such as selecting patients with positive and reproducible stress tests and little in the way of spontaneously occurring angina versus selecting patients with positive but variable stress tests and frequent episodes of spontaneously induced angina. The former group may reflect pure fixed coronary artery disease with little in the way of vasospasm, or change in vasomotor tone, while the latter group may reflect greater variability in vasomotor tone and/or more in the way of plaque instability. The clinical efficacy of long acting nitrates might therefore be expected to be greatest in those patients with larger numbers of spontaneously occurring angina episodes. Recent data suggest that nitrates may have important direct effects on coronary vessels including dilating eccentric coronary stenoses, dilating intercoronary collateral channels and having greater dilating effects on more diseased segments as opposed to less diseased coronary segments.(ABSTRACT TRUNCATED AT 400 WORDS)

Progression of coronary artery disease after percutaneous transluminal coronary angioplasty

Thirty-nine patients underwent coronary arteriography 1 to 20 months (mean 7 months) after percutaneous transluminal coronary angioplasty (PTCA). At the time of the repeat study 65 patients (90%) had recurrent angina or myocardial infarction, and 4 patients (10%) were asymptomatic. Restenosis, defined as >50% loss of PTCA gained diameter, was found in 19 patients (49%). In addition, 20 patients had new lesions or marked progression of existing lesions (defined as >20% or increasing >20% obstruction in coronary ciameter) in the previously normal or mildly diseased coronary segments. The new or progressive lesions occurred both in patients with restenosis at the PTCA site (nine of 19) and in patients without restenosis (91 of 20). New or progressive lesions tended to occur more commonly in the artery on which PTCA was performed (13 of 40) than in the artery that did not have PTCA (10 of 77) ( p < 0.02 by χ 2). In arteries that had PTCA, new or progressive lesions occurred more often in the segment proximal to the angioplasty site (seven to 13 or 54%) than in the peri-PTCA segment (two of 13 or 15%) and in the segments distal to it (four of 13 or 31%), but this observation did not reach statistical significance. No other clinical, angiographic, or PTCA procedure variables affected the occurrence of new or progressive lesions. In patients with recurrent angina or myocardial infarction after PTCA, both restenosis and new or progressive lesions are common. New lesions or marked progression of existing lesion tended to occur in the vessel subjected to PTCA. Arterial trauma during the PTCA procedure could be considered a possible mechanism for progression of coronary artery disease after coronary angioplasty.

Evaluation of diseased coronary arterial branches by polar representations of thallium-201 rotational myocardial imaging.

The perfusion territories in polar representations of stress Tl-201 rotational myocardial imaging in patients with angina pectoris who had one diseased coronary segment were analyzed. The lesions proximal or distal to the first major septal perforator in left anterior descending arteries were detected by the presence or absence of defects at the base of the anterior septum. Right coronary artery lesions were detected by the presence of defects at the basal posterior septum, in contrast to the preservation of myocardial uptake at this portion in lesions of the left circumflex artery. The specific defect patterns were detected in cases with lesions at the first diagonal, obtuse marginal, and posterolateral branches. Recognition of these defects in the polar maps allows detailed detection of diseased coronary arterial branches.

Coronary artery dilation and hemodynamic responses after isosorbide dinitrate therapy in patients with coronary artery disease

The response to sublingual isosorbide dinitrate (ISDN) was studied in 10 men with suspected coronary artery disease undergoing coronary arteriography. A Swan-Ganz catheter was placed in the pulmonary artery to record hemodynamic response. Diseased coronary segments were identified during routine Judkins selective coronary angiograms. Sublingual isosorbide dinitrate (ISDN) (5 or 10 mg) was then given with the catheters in place. Multiple sequential single-view coronary angiograms and pulmonary and systemic hemodynamic responses were recorded over 30 minutes after drug administration. At 30 minutes, there was a 53% reduction (p < 0.01) in pulmonary capillary wedge pressure and a 15% decrease (p < 0.05) in systemic and pulmonary vascular resistance, with a net 13% decrease (p < 0.01) in cardiac output and 20% decrease (p < 0.01) in mean arterial pressure. Quantitative arteriography demonstrated substantial dilation of luminal cross-sectional area in both normal and diseased coronary arterial segments. Normal epicardial segments were grouped according to luminal area (1 to 4, 4 to 8 and more than 8 mm 2) and demonstrated maximal area dilation at 10 minutes of 55% (p < 0.01), 29% (p < 0.01) and 16% (p < 0.05), respectively. Diseased epicardial segments (stenosis 50% or greater) dilated 51% (p < 0.01) at 10 minutes. Calculated stenosis resistance decreased 40% (p < 0.01). Diseased segments in small and middle-sized arteries (1 to 8 mm 2) are 4 times more reactive than those in larger arteries (more than 8 mm 2), with peak dilation of 77 vs 21% (p < 0.01) at 30 minutes. These responses occurred within 3 minutes after ISDN administration, peaked at 10 minutes and persisted, unchanged, for the remaining 20 minutes. The response of epicardial arteries to ISDN is the maximum observed with any coronary vasodilating drug.