Richard A. Kerensky

Abnormal Coronary Vasomotion as a Prognostic Indicator of Cardiovascular Events in Women Results From the National Heart, Lung, and Blood Institute–Sponsored Women’s Ischemia Syndrome Evaluation (WISE)

Background—Coronary vascular dysfunction has been linked to atherosclerosis and adverse cardiovascular outcomes in men, but these relationships have not been firmly established in women. Methods and Results—As part of the Women’s Ischemia Syndrome Evaluation (WISE) sponsored by the National Heart, Lung, and Blood Institute, 163 women referred for clinically indicated coronary angiography underwent coronary reactivity assessment with quantitative coronary angiography and intracoronary Doppler flow before and after intracoronary administration of acetylcholine, adenosine, and nitroglycerin and were then followed up for clinical outcomes. History of hypertension was present in 61%, dyslipidemia in 54%, diabetes in 26%, and current tobacco use in 21% of women enrolled. Seventy-five percent had no or only mild epicardial coronary artery disease (CAD). Over a median follow-up of 48 months, events occurred in 58 women. On bivariate analysis, women with an event had significantly less change in coronary cross-sectional area (&Dgr;CSA) in response to acetylcholine (P =0.0006) and nitroglycerin (P =0.04). In addition, women with abnormal coronary dilator response to acetylcholine had less time free from cardiovascular events (P =0.004). In multivariable analysis, after controlling for age, hypertension, diabetes, dyslipidemia, tobacco use, and CAD severity, %&Dgr;CSA with acetylcholine (P =0.001) independently predicted events. When the outcome was restricted to only death, myocardial infarction, congestive heart failure, and stroke, %&Dgr;CSA with acetylcholine remained a significant predictor (P =0.006). Conclusions—In women in this study, impaired coronary vasomotor response to acetylcholine was independently linked to adverse cardiovascular outcomes regardless of CAD severity.

Detailed angiographic analysis of women with suspected ischemic chest pain (pilot phase data from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation [WISE] Study Angiographic Core Laboratory).

The purpose of this study is to provide a contemporary qualitative and quantitative analysis of coronary angiograms from a large series of women enrolled in the Womens Ischemia Syndrome Evaluation (WISE) study who had suspected ischemic chest pain. Previous studies have suggested that women with chest pain have a lower prevalence of significant coronary artery disease (CAD) compared with men. Detailed analyses of angiographic findings relative to risk factors and outcomes are not available. All coronary angiograms were reviewed in a central core laboratory. Quantitative measurement of percent stenosis was used to assess the presence and severity of disease. Of the 323 women enrolled in the pilot phase, 34% had no detectable, 23% had measurable but minimal, and 43% had significant ( > 50% diameter stenosis) CAD. Of those with significant CAD, most had multivessel disease. Features suggesting complex plaque were identified in < 10%. Age, hypertension, diabetes mellitus, prior myocardial infarction (MI), current hormone replacement therapy, and unstable angina were all significant, independent predictors of presence of significant disease (p < 0.05). Subsequent hospitalization for a cardiac cause occurred more frequently in those women with minimal and significant disease compared with no disease (p = 0.001). The common findings of no and extensive CAD among symptomatic women at coronary angiography highlight the need for better clinical noninvasive evaluations for ischemia. Women with minimal CAD have intermediate rates of rehospitalization and cardiovascular events, and thus should not be considered low risk.

Coronary flow velocity response to adenosine characterizes coronary microvascular function in women with chest pain and no obstructive coronary disease ☆: Results from the pilot phase of the Women’s Ischemia Syndrome Evaluation (WISE) Study

OBJECTIVES We sought to develop and validate a definition of coronary microvascular dysfunction in women with chest pain and no significant epicardial obstruction based on adenosine-induced changes in coronary flow velocity (i.e., coronary velocity reserve). BACKGROUND Chest pain is frequently not caused by fixed obstructive coronary artery disease (CAD) of large vessels in women. Coronary microvascular dysfunction is an alternative mechanism of chest pain that is more prevalent in women and is associated with attenuated coronary volumetric flow augmentation in response to hyperemic stimuli (i.e., abnormal coronary flow reserve). However, traditional assessment of coronary volumetric flow reserve is time-consuming and not uniformly available. METHODS As part of the Womens Ischemia Syndrome Evaluation (WISE) study, 48 women with chest pain and normal coronary arteries or minimal coronary luminal irregularities (mean stenosis = 7%) underwent assessment of coronary blood flow reserve and coronary flow velocity reserve. Blood flow responses to intracoronary adenosine were measured using intracoronary Doppler ultrasonography and quantitative angiography. RESULTS Coronary volumetric flow reserve correlated with coronary velocity reserve (Pearson correlation = 0.87, p < 0.001). In 29 (60%) women with abnormal coronary microcirculation (mean coronary flow reserve = 1.84), adenosine increased coronary velocity by 89% (p < 0.001) but did not change coronary cross-sectional area. In 19 (40%) women with normal microcirculation (mean flow reserve = 3.24), adenosine increased coronary velocity and area by 179% (p < 0.001) and 17% (p < 0.001), respectively. A coronary velocity reserve threshold of 2.24 provided the best balance between sensitivity and specificity (90% and 89%, respectively) for the diagnosis of microvascular dysfunction. In addition, failure of the epicardial coronary to dilate at least 9% was found to be a sensitive (79%) and specific (79%) surrogate marker of microvascular dysfunction. CONCLUSIONS Coronary flow velocity response to intracoronary adenosine characterizes coronary microvascular function in women with chest pain in the absence of obstructive CAD. Attenuated epicardial coronary dilation response to adenosine may be a surrogate marker of microvascular dysfunction in women with chest pain and no obstructive CAD.

Revisiting the culprit lesion in non–Q-wave myocardial infarction ☆: Results from the VANQWISH trial angiographic core laboratory

OBJECTIVE We sought to determine the underlying coronary anatomy and characterize the culprit lesion after non-Q-wave myocardial infarction (NQWMI). BACKGROUND Although the culprit lesion and infarct-related artery often are easily identified with coronary angiography after Q-wave MI, the culprit lesion after NQWMI has not been well characterized. Small retrospective studies have suggested that the absence of Q-waves on an electrocardiogram is due to incomplete occlusion of the infarct-related artery. METHODS Coronary angiograms from 350 patients randomized to the early invasive strategy in the Veterans Affairs Non-Q-Wave Infarction Strategies in-Hospital (VANQWISH) trial were systematically analyzed in an angiographic core laboratory. A consensus panel identified the culprit lesion and the infarct-related artery using prespecified criteria for complex lesion morphology and acute versus chronic occlusions. Severity of angiographic disease and left ventricular function also were analyzed. Patients with a single identified culprit lesion were compared with those who had multiple apparent culprits and those without an identifiable culprit lesion. RESULTS A single culprit lesion was identified in only 49% of patients undergoing early angiography after NQWMI. The majority of patients either had no identifiable culprit (37%) or multiple apparent culprit lesions (14%). A single incomplete occlusion of the infarct-related artery was found in only 36% of patients, and an isolated acute occlusion of the infarct-related artery occurred in 13%. Patients without an identifiable culprit lesion had severe coronary disease (obstructive coronary artery disease [CAD] in 84%) but no complex lesion morphology. There was no difference in angiographic severity of disease comparing patients with and without identifiable culprit lesions. Patients with a single incomplete occlusion of the infarct-related artery were more likely to undergo percutaneous transluminal coronary angioplasty than other patients, whereas patients with multiple culprit lesions were more frequently treated with coronary artery bypass grafting. CONCLUSIONS Coronary angiography early after NQWMI frequently identifies severe obstructive CAD, but a single identifiable culprit lesion was identified in <50% of patients. Multiple culprit lesions were seen in 14% of patients. An angiographic culprit lesion could not be identified in more than one-third of patients undergoing coronary angiography as part of an invasive strategy.

Constrictor and dilator responses to intracoronary acetylcholine in adjacent segments of the same coronary artery in patients with coronary artery disease. Endothelial function revisited.

BACKGROUND In patients with angiographically detectable atherosclerosis or in those with risk factors for coronary artery disease, intracoronary acetylcholine causes coronary constriction instead of endothelium-derived relaxing factor-mediated dilation. Therefore, it has been hypothesized that diffuse endothelial dysfunction precedes development of coronary atherosclerosis. We tested this hypothesis in a systematic investigation of the effects of ascending doses of acetylcholine on the diameters of nonstenotic segments of the left coronary artery in patients with advanced atherosclerosis and coronary risk factors. METHODS AND RESULTS Effects of intracoronary infusion of acetylcholine (10(-6) to 10(-4) mol/L) on diameters of proximal, middle, and distal nonstenotic segments of the left coronary artery were studied in 28 consecutive patients with chronic stable angina, positive exercise tests, and angiographic evidence of obstructive atherosclerosis (> or = 50% reduction in lumen diameter in at least one vessel). Two patterns of response to the maximal acetylcholine dose (10(-4) mol/L) were observed. In 21 patients (group 1), only constriction was observed in all left anterior descending and circumflex artery segments studied (16 +/- 3%, 19 +/- 4%, and 23 +/- 4%, respectively; P < .01 compared with control). In 7 other patients (group 2), both constriction and dilation were observed in adjacent segments of the same vessel; maximal acetylcholine dose caused constriction in 14 left anterior descending artery segments from a control diameter of 1.94 +/- 0.19 to 1.33 +/- 0.26 mm (37% reduction, P < .01) and dilation in 16 other segments from 1.63 +/- 0.22 to 1.93 +/- 0.21 mm (25% increase, P < .01). In the circumflex artery, this dose caused constriction in 16 segments from a control diameter of 1.88 +/- 0.14 to 1.33 +/- 0.17 mm (31% reduction, P < .01) and dilation in 12 segments from 1.37 +/- 0.12 to 1.71 +/- 0.09 mm (34% increase, P < .01). CONCLUSIONS In 25% of patients studied with advanced angiographic coronary atherosclerosis and coronary risk factors, coronary segments with acetylcholine-inducible dilatation are present. In these patients, the endothelium is not diffusely dysfunctional as currently believed but rather shows marked segmental heterogeneity in the response to acetylcholine reflecting degrees of endothelial dysfunction.

Systolic compression of the left anterior descending coronary artery: a case series, review of the literature, and therapeutic options including stenting.

Six cases in our institution of various presentations of left anterior descending (LAD) myocardial bridging were found on coronary angiography. Generally a benign condition, this finding can result in ischemia or infarction as seen in some of our cases. We found one case in which the bridge resulted in an anterior myocardial infarction in an elderly patient, one case with fixed stenoses at the entry and exit point of the bridge causing ischemia, another with vasospasm within the bridged segment, one case in which the patient was referred for intervention of a fixed stenosis which after intracoronary nitroglycerin (NTG) was found to be an LAD bridge, another case in which the thallium myocardial perfusion scan revealed a reversible anterior defect, and finally one case with anginal chest pain despite a normal coronary flow reserve proximal and distal to the bridged segment. Our treatments varied from stenting in three patients to medical therapy in the remaining patients. We concluded that a thorough evaluation in this population should include functional testing for ischemia, intravascular ultrasound to assess wall thickness, and coronary flow reserve measurements in order to determine the significance of the these bridges. Stenting may have a role in select patients. However, additional studies are needed. Cathet Cardiovasc Intervent 2002;56:58–63.

Percutaneous coronary intervention versus medical therapy for coronary allograft vasculopathy: One center’s experience

BACKGROUND Coronary allograft vasculopathy, a rapidly progressive form of atherosclerosis, remains the limiting factor in the long-term survival of heart transplant recipients. Some centers have attempted percutaneous coronary intervention to slow the disease process and thereby reduce mortality in these patients, but long-term follow-up data are scarce. We compared clinical outcomes in heart transplant recipients with coronary allograft vasculopathy who were treated either with percutaneous coronary intervention or with aggressive medical therapy alone. METHODS A retrospective analysis of all heart transplant recipients at our institution who underwent surveillance coronary angiography for coronary allograft vasculopathy between 1995 and 2000 was performed. Patients with coronary allograft vasculopathy were stratified according to whether they received medical therapy or percutaneous coronary intervention. Baseline demographics, results of re-vascularization procedures and outcomes were analyzed. RESULTS From 1995 to 2000, 301 patients underwent 602 coronary angiograms. Of the 79 patients who had angiographic evidence of coronary allograft vasculopathy, 53 were treated with aggressive medical therapy, while 26 underwent percutaneous coronary intervention in addition to aggressive medical therapy. At baseline, patients treated with aggressive medical therapy tended to be younger (54.6 +/- 13.8 years) than patients treated with percutaneous coronary intervention (62.6 +/- 7.6 years; p = 0.0079). Ejection fraction at time of diagnosis of coronary allograft vasculopathy was similar for both groups (medical therapy group, 44.4 +/- 13.4% vs percutaneous coronary intervention group, 47.2 +/- 12.7%; p = 0.38). In our cohort, heart transplant recipients with coronary allograft vasculopathy demonstrated greater mortality than heart transplant recipients without coronary allograft vasculopathy (p = 0.016). Patients who underwent percutaneous coronary intervention had a 60% re-stenosis rate at 6 months if they were treated with coronary angioplasty and an 18% re-stenosis rate if they received a coronary stent. Kaplan-Meier analysis showed no significant difference in survival in either treatment group at 1 year (80% for medical therapy group vs 95% for percutaneous coronary intervention group) or 3 years (68% for medical therapy group vs 79% for percutaneous coronary intervention group) after the angiographic diagnosis of coronary allograft vasculopathy. CONCLUSION In this non-randomized trial, heart transplant recipients with coronary allograft vasculopathy were less likely to survive than patients without it. In addition, we found no statistical difference in mortality in heart transplant recipients with coronary allograft vasculopathy, regardless of whether they received percutaneous coronary intervention or aggressive medical therapy alone.

Pharmacologic plaque passivation for the reduction of recurrent cardiac events in acute coronary syndromes

Acute coronary syndrome (ACS) is often associated with the rupture of vulnerable atherosclerotic plaque, coronary thrombus formation, and abrupt limitation of blood flow, leading to adverse outcomes. Passivation of vulnerable plaque represents a therapeutic concept that has the potential to prevent or limit the magnitude of a new rupture in order to reduce the recurrence or severity of events. Plaque passivation can be defined as a process by which the structure or content of the atherosclerotic plaque is changed to reduce the risk of subsequent rupture and thrombosis. This may be achieved by using strategies that address different components of the plaque or the endothelium. The following factors can affect the susceptibility of plaque to rupture: macrophage infiltration; accumulation of inflammatory cells; paracrine secretion of enzymes that may cause degradation of the fibrous cap of coronary plaque; shear stress; circadian rhythm variation in stress hormone release; and infectious agents. The use of pharmacologic agents to reduce plaque vulnerability by passivation has been explored. Clinical studies demonstrate that lipid-modifying agents (e.g., statins), antiplatelet agents (acetylsalicylic acid, thienopyridines, thianopyridines, glycoprotein IIb/IIIa inhibitors), and antithrombotic agents (unfractionated heparin and low-molecular-weight heparin) can reduce the occurrence of acute coronary events in ACS patients. In addition, angiographic studies suggest that statins may also promote regression of atherosclerosis. Angiotensin-converting enzyme inhibitors, niacin, and calcium antagonists may also contribute to plaque passivation. This article reviews atherosclerotic plaque development and vulnerability and discusses some clinical studies highlighting the role of plaque passivation in the management of ACS patients.

American College of Cardiology/ European Society of Cardiology international study of angiographic data compression phase I: The effects of lossy data compression on recognition of diagnostic features in digital coronary angiography

OBJECTIVES This study intended to determine the effect of varying degrees of lossy Joint Photographic Experts Group (JPEG) compression on detection of coronary angiographic features. BACKGROUND Compression of digital coronary angiograms facilitates playback of images and decreases cost. There are little data on the effect of compression on the accuracy of coronary angiography. METHODS At six centers, 71 angiographers each reviewed a set of 100 angiographic sequences. The 100 sequences were divided into four, 25-sequence subsets. Each subset of 25 was displayed either as original images or at one of three compression ratios (CRs) (6:1, 10:1 or 16:1). The effect of lossy compression on the sensitivity and specificity for detection of diagnostic features was determined. The effect of compression on subjective measures of image quality graded by the angiographers was also examined. RESULTS Lossy compression at a ratio of 16:1 decreased the sensitivity for the detection of diagnostic features (76% vs. 80% p = 0.004). The largest effect was in the detection of calcification (52% vs. 63% at 16:1 compression vs. original images, p < 0.001). Subjective indicators of image quality indicated a reduction in confidence in interpretation at CRs of 10:1 and 16:1. CONCLUSIONS With increased ratios of lossy compression, a degradation of digital coronary angiograms occurs that results in decreased diagnostic accuracy. The sensitivity for detection of common diagnostic features was decreased, and subjective assessment of image quality was impaired. Caution is warranted in the interpretation of coronary angiograms that have been subjected to lossy JPEG compression beyond a ratio of 6:1.

Effect of theophylline on the warm-up phenomenon

This study examined whether the adenosine receptor antagonist theophylline prevents the warm-up phenomenon in patients with stable angina undergoing serial exercise tests. Our findings offer evidence that adenosine does not play a role in the warm-up phenomenon, and indirectly suggest that the warm-up phenomenon does not represent ischemic preconditioning in humans.