Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction.

BACKGROUND: Coronary endothelial dysfunction is characterized by vasoconstrictive response to the endothelium-dependent vasodilator acetylcholine. Although endothelial dysfunction is considered an early phase of coronary atherosclerosis, there is a paucity of information regarding the outcome of these patients. Thus, this study was designed to evaluate the outcome of patients with mild coronary artery disease on the basis of their endothelial function. METHODS AND RESULTS: Follow-up was obtained in 157 patients with mildly diseased coronary arteries who had undergone coronary vascular reactivity evaluation by graded administration of intracoronary acetylcholine, adenosine, and nitroglycerin and intracoronary ultrasound at the time of diagnostic study. Patients were divided on the basis of their response to acetylcholine into 3 groups: group 1 (n=83), patients with normal endothelial function; group 2 (n=32), patients with mild endothelial dysfunction; and group 3 (n=42), patients with severe endothelial dysfunction. Over an average 28-month follow-up (range, 11 to 52 months), none of the patients from group 1 or 2 had cardiac events. However, 6 (14%) with severe endothelial dysfunction had 10 cardiac events (P<0.05 versus groups 1 and 2). Cardiac events included myocardial infarction, percutaneous or surgical coronary revascularization, and/or cardiac death. CONCLUSIONS: Severe endothelial dysfunction in the absence of obstructive coronary artery disease is associated with increased cardiac events. This study supports the concept that coronary endothelial dysfunction may play a role in the progression of coronary atherosclerosis.

Application of the New York State PTCA mortality model in patients undergoing stent implantation.

BACKGROUND: This study applied the New York State conventional coronary angioplasty (PTCA) model of clinical outcomes to evaluate whether it has relevance in the current era of stent implantation. The model was developed in 62 670 patients treated with conventional PTCA from 1991 to 1994 to risk adjust mortality and bypass surgery after PTCA. Since then, stents have become the dominant form of intervention. Whether that model remains relevant is uncertain. METHODS AND RESULTS: All patients undergoing stenting at the Mayo Clinic from 1995 to 1998 were analyzed for in-hospital mortality, bypass surgery performed after attempted stenting, and longer-term mortality. No patients were excluded. The New York model was used to risk adjust and predict in-hospital and follow-up mortality. There were 3761 patients with 4063 procedural admissions for stenting; 6,472 target vessel segments were attempted, and 96.1% of procedures were successful. With the New York multivariable risk factor equation, 79 in-hospital deaths were expected (1.95%); 66 deaths (1.62%) were observed. The New York model risk score in a logistic regression model was the most significant factor associated with in-hospital mortality (OR, 1.86; P<0.001). During a mean follow-up of 1.2+/-1.0 years, there were 154 deaths. Multivariable analysis documented 6 factors associated with subsequent mortality; New York risk score was the most significant (chi(2)=16.64, P=0.0001). CONCLUSIONS: Although the New York mortality model was developed in an era of conventional angioplasty, it remains relevant in patients undergoing stenting. The risk score derived from that model is the variable most significantly associated with not only in-hospital but also longer-term outcome.

Attenuated coronary flow reserve and vascular remodeling in patients with hypertension and left ventricular hypertrophy.

OBJECTIVES: The purpose of this study was to evaluate the association between hypertension and left ventricular hypertrophy (LVH) with both coronary vascular remodeling and endothelial function. BACKGROUND: The association between endothelial and nonendothelial coronary flow reserve with vascular remodeling in patients with hypertension and LVH is still unclear. METHODS: One hundred and eleven patients with normal or mildly diseased coronary arteries at angiography underwent intravascular ultrasound examination of the left anterior descending coronary artery. Patients were divided into three groups: group 1: n = 13, hypertensive patients with LVH; group 2: n = 30, hypertensive patients without LVH; group 3: n = 68, normotensive patients. Vessel and lumen area and atherosclerotic plaque area were evaluated. Vascular reactivity was examined using intracoronary adenosine and acetylcholine. RESULTS: Vessel area in group 1 (with LVH) was significantly (p < 0.01) greater than that in group 2 (without LVH), whereas, vessel area in both groups 1 and 3 was similar (12.8 +/- 0.8 mm2, 10.7 +/- 0.4 mm2 and 11.5 +/- 0.3 mm2). Coronary blood flow at baseline for patients in group 1 (with LVH) was significantly greater than it was for patients in groups 2 and 3 (81.1 +/- 9.9 ml/min, 56.5 +/- 6.2 ml/min and 48.1 +/- 3.2 ml/min, both p < 0.05). In comparison with groups 2 and 3, the response to both acetylcholine and adenosine was significantly impaired in patients with LVH. CONCLUSIONS: The current study demonstrates that hypertension with LVH is associated with both coronary vascular remodeling and attenuated endothelial and nonendothelial coronary flow reserve.

Obesity is independently associated with coronary endothelial dysfunction in patients with normal or mildly diseased coronary arteries.

OBJECTIVES: This study evaluates the impact of obesity on coronary endothelial function in patients with normal or mild coronary artery disease. BACKGROUND: The American Heart Association (AHA) has recently classified obesity as a modifiable risk factor for coronary heart disease. METHODS: A total of 397 consecutive patients with normal or mildly diseased coronary arteries at angiography underwent coronary vascular reactivity evaluation using intracoronary adenosine, acetylcholine and nitroglycerin. Patients were divided into three groups based on the body mass index (BMI): Group 1, patients with a BMI <25 (n = 117, normal weight); Group 2, patients with a BMI 25-30 (n = 149, overweight) and Group 3, patients with a BMI >30 (n = 131, obese). RESULTS: There were no significant differences among the groups in regard to other cardiovascular risk factors, except that overweight but not obese patients were significantly older than normal-weight patients (47 +/- 1 years in Group 1, 53 +/- 1 years in Group 2 and 50 +/- 1 years in Group 3, p < 0.001). The percent change of coronary blood flow to acetylcholine (%delta CBF Ach) was significantly lower in the obese patients than in the normal-weight group (85.2 +/- 12.0% in Group 1, 63.7 +/- 10.0% in Group 2 and 38.1 +/- 9.6% in Group 3, p = 0.009). By multivariate analysis, overweight (odds ratio, 1.55; 95% confidence interval, 1.2-2.0) and obesity (odds ratio, 2.41; 95% confidence interval, 1.5-4.0) status were independently associated with impaired coronary endothelial function. CONCLUSIONS: The study demonstrates that obesity is independently associated with coronary endothelial dysfunction in patients with normal or mildly diseased coronary arteries.

Epicardial vasomotor responses to acetylcholine are not predicted by coronary atherosclerosis as assessed by intracoronary ultrasound.

OBJECTIVES: The purpose of this study was to use intravascular ultrasound to determine the morphologic appearance of the coronary arteries, relating the absence, presence and extent of atherosclerosis to the response of the coronary arteries to acetylcholine infusion. BACKGROUND: Endothelial function plays a major role in the pathophysiology of myocardial ischemia and angina pectoris. The response of the coronary arteries to selective infusion of acetylcholine has been used to examine endothelial function, with vasoconstriction occurring in the absence of intact endothelial function. Vasoconstriction to acetylcholine infusion in humans without overt coronary artery disease has been attributed to early atherosclerosis not detected by coronary angiography. METHODS: Twenty-nine patients without overt coronary artery disease underwent selective coronary angiography and selective intracoronary infusion of increasing concentrations of acetylcholine (10(-6), 10(-5) and 10(-4) mol/liter), followed by intravascular ultrasound imaging. RESULTS: The response of the coronary arteries to acetylcholine infusion was not dependent on the absence or presence of atherosclerotic plaque, as detected by intravascular ultrasound. The percent change in epicardial coronary artery diameter during acetylcholine infusion versus baseline was -14 +/- 28% (mean +/- SD) in the seven patients with no visible atherosclerosis on intravascular ultrasound versus -9 +/- 20% in the 22 patients with visible atherosclerosis on intravascular ultrasound (p = NS, confidence interval -14% to 25%). There was a greater vasoconstrictive response to acetylcholine infusion in patients with risk factors for coronary artery disease than in those without risk factors (p = 0.003). CONCLUSIONS: The vasoreactive response to acetylcholine is not necessarily dependent on ultrasound detection of the presence or absence of atherosclerosis.

Measuring maximal percent area stenosis poststent placement with intracoronary Doppler and the continuity equation and correlation with intracoronary ultrasound and angiography.

Quantitative coronary angiography (QCA) and intracoronary ultrasound (ICUS) are methods for anatomic assessment of stent deployment. Intracoronary Doppler is primarily a method for the physiologic assessment of coronary stenoses. It correlates well with traditional noninvasive measurements of lesion significance. Intracoronary Doppler was used for the anatomic assessment of de novo coronary artery stenosis with variable success; however, its use for anatomic assessment of adequate stent deployment is unavailable. A rapid, automated software program was developed based on a modified continuity equation to calculate the maximal in-stent percent area stenosis by comparing the maximal in-stent velocity to an average reference velocity (proximal and distal). This study was designed to compare the Doppler method of an anatomic assessment with QCA and ICUS in 15 patients. Physiologic success of stent deployment was determined by the distal coronary flow reserve to 24 to 36 microg of intracoronary adenosine. Following successful stent deployment, distal coronary flow reserve increased significantly from a baseline of 1.6 +/- 0.5 to 2.9 +/- 1.1. There was a significant correlation between the maximal in-stent percent area stenosis as measured by Doppler and both QCA (r = 0.78, p <0.01) and ICUS (r = 0.84, p <0.01). This study demonstrates that maximal in-stent percent area stenosis can be measured by intracoronary Doppler and a novel software program. The intracoronary Doppler guidewire method can assess the adequacy of stent deployment using both anatomic and physiologic principles and may supplement other quantitative methodologies.

Variability of myocardium at risk for acute myocardial infarction.

The objective of this study was to assess the variability in myocardium at risk and relate this to coronary angiographic variables. One hundred ninety-seven patients with > or = 1-mm ST-segment elevation in 2 contiguous electrocardiographic leads, without prior myocardial infarction, were injected with technetium-99m sestamibi acutely before reperfusion therapy. The perfusion defect was quantified to determine myocardium at risk for infarction. Patients underwent coronary angiography to determine the infarct-related artery and to classify the occlusion as proximal or not proximal. Collateral and anterograde (Thrombolysis In Myocardial Infarction [TIMI] trial) flow were assessed in a subset of 83 patients with angiography before direct angioplasty. Myocardium at risk for infarction in the distribution of the left anterior descending coronary artery was significantly greater (p <0.0001) than that in the circumflex or right coronary artery. In the left anterior descending coronary artery distribution, myocardium at risk for infarction was significantly larger for proximal occlusions (p <0.0001). There was a trend toward greater myocardium at risk for infarction of proximal occlusions (p = 0.14) of the left circumflex but not for proximal occlusions in the right coronary artery distribution (p = 0.47). Multivariate analysis revealed that the infarct-related artery (p <0.0001), TIMI flow (p = 0.0002), and proximal location (p = 0.09) in the infarct-related artery were independent predictors of myocardium at risk for infarction. Thus, infarct-related artery, TIMI flow, and proximal location of occlusion in the infarct-related artery influence the myocardium at risk for infarction, which is highly variable for given location of occlusion.

Utility of rate histograms in programming and follow-up of a DDDR pacemaker.

Dual-chamber, rate-modulated pacing (DDDR) is the newest available pacing mode. To optimize programming of the rate response options for such a pacemaker, the physician must adopt an organized follow-up method, including use of some type of exercise testing to assess the programmed options of the pacemaker. Because the patient may achieve a substantial "training effect" after a rate-modulated pacing device has been implanted, the device probably should be reprogrammed at 1 month or after implantation. Programming and follow-up can be considerably facilitated by the use of pacemaker-generated "rate histograms," which conveniently display the distribution of rate responses to various levels of activity.

Advantage of discrepant upper rate limits in a DDDR pacemaker.

The latest cardiac pacing mode to become available is the dual-chamber, rate-modulated mode (referred to as DDDR), which restores both rate responsiveness and atrioventricular synchrony in patients with sinus node dysfunction and atrioventricular block. This pacing mode combines dual-chamber and single-chamber rate-modulated technologies. Thus, it is necessary to program both a maximum tracking rate and a maximum sensor rate, as in dual-chamber and single-chamber rate-modulated devices, respectively. These two upper rate limits are usually programmed to equivalent values. The case described herein illustrates one advantage of programming discrepant upper rate limits. The rapid tracking of supraventricular tachycardias was prevented by lowering the maximum tracking rate to 100 ppm. A maximum sensor rate of 140 ppm still allowed an adequate rate response during activity.

Use of intracoronary ultrasound imaging for assessing left main coronary artery disease.

Coronary angiography has many limitations for the assessment of coronary artery disease. Intracoronary ultrasound imaging may overcome some of these limitations by providing direct visualization of the luminal area and plaque morphologic features. Although the size of the currently available intracoronary ultrasound catheters precludes their use in many diseased coronary vessels, lesions in the relatively large vessels, such as the left main coronary artery, can be readily assessed. Intracoronary ultrasound imaging was performed in five patients in whom the status of the left main coronary artery was unclear after conventional coronary angiography. Qualitative assessment of atherosclerotic involvement and quantitative analysis of the absolute luminal area and the percentage of area of stenosis were performed. No complications were associated with the intracoronary ultrasound procedure. In all five patients, the ultrasound studies provided additional information on which a clinical decision could be made. Intracoronary ultrasound imaging is useful for assessing disease of the left main coronary artery in selected patients in whom current angiographic techniques have provided equivocal results.

Pathophysiology, diagnosis, and current management strategies for chest pain in patients with normal findings on angiography.

Chest pain syndromes in patients with normal angiographic findings represent a multifactorial pathophysiologic state, which may range from abnormalities in pain perception to abnormalities in endothelial- and non-endothelial-dependent coronary flow reserve associated with myocardial ischemia. Treatment begins with an accurate diagnosis by obtaining a comprehensive history and performing a physical examination, followed possibly by performing functional angiography in those who continue to have symptoms. This approach may help to determine appropriate treatment.

The mechanism of blood flow during closed chest cardiac massage in humans: transesophageal echocardiographic observations.

Despite years of research, the mechanism of forward blood flow during closed chest cardiac massage remains controversial. Two theories have been suggested: the cardiac pump theory and the thoracic pump theory. Transesophageal echocardiography offers a new approach for study of the flows and cardiac morphologic features during chest compressions in humans. Case reports are presented to illustrate the use of transesophageal echocardiography during cardiopulmonary resuscitation. The findings included right and left ventricular compression, closure of the mitral valve during compression, opening of the mitral valve during the release phase, and atrioventricular valvular regurgitation during compression, indicating a positive ventricular-to-atrial pressure gradient. These findings suggest that direct cardiac compression was the predominant mechanism of forward blood flow during cardiopulmonary resuscitation in these patients. An understanding of the actual mechanisms involved is necessary if improved cardiopulmonary resuscitative techniques or adjuncts are to be rationally developed for enhancing the outcome of resuscitation.

Prevalence of coronary blood flow reserve abnormalities among patients with nonobstructive coronary artery disease and chest pain.

OBJECTIVE: To determine the prevalence of abnormalities in endothelium-dependent and endothelium-independent coronary flow reserve among patients with non-obstructive coronary artery disease and chest pain. MATERIAL AND METHODS: We studied endothelium-dependent (after infusion of 10(-6) M to 10(-4) M of acetylcholine) and endothelium-independent (after administration of 18 to 36 micrograms of adenosine) coronary flow reserve among patients with nonobstructive coronary artery disease and chest pain who were undergoing assessment at Mayo Clinic Rochester. Coronary blood flow was derived from coronary artery diameter assessed by quantitative angiography and Doppler flow velocities. RESULTS: The cohort consisted of 203 patients (158 female and 45 male patients), who ranged in age from 17 to 78 years (mean, 51). Most patients (92%) had at least one risk factor for atherosclerosis; a substantial proportion had undergone extensive cardiac and noncardiac evaluation. Whereas 41.5% of the patients had normal coronary flow reserve, 58.5% had an abnormal response: 11.3% an impaired response to adenosine (flow velocity ratio of 2.5 or less), 29.2% an impaired response to acetylcholine (flow reserve ratio of 1.5 or less), and 18% a combined abnormality. No correlation (r2 = 0.03) was noted between endothelium-dependent and endothelium-independent flow reserve. CONCLUSION: Most study patients with chest pain and nonobstructive coronary artery disease undergoing coronary vasomotor evaluation had risk factors for coronary artery disease and diverse abnormalities in endothelium-dependent or endothelium-independent coronary flow reserve (or both). These findings underscore the need for a comprehensive assessment.

Methylergonovine-induced diffuse coronary spasm in a patient with exercise-induced coronary spasm after heart transplantation.

Coronary artery spasm is a rarely reported condition after heart transplantation. We report a case of exercise-induced coronary artery spasm in a patient 1-year after orthotopic heart transplantation. Serial quantitative coronary angiography showed significant diffuse loss of luminal diameter. Provocative testing with intracoronary acetylcholine and intravenous methylergonovine maleate was performed in an effort to document efficacy of the antispasm regimen. Infusion of acetylcholine into the left anterior descending coronary artery resulted in transient closure of the vessel. Diffuse spasm resulting in hypotension and ventricular fibrillation occurred with intravenous methylergonovine maleate administration. Because of the risk of provoking diffuse spasm, intravenous administration of methylergonovine maleate should be avoided in the posttransplantation setting. Review of the literature suggests that coronary artery spasm after transplantation is often associated with severe transplant coronary artery disease and may be associated with a poor prognosis. Coronary artery spasm may be a more common cause of syncope and death after transplantation than it is currently thought to be.

Intravascular ultrasound to assess anastomotic patency after lung transplantation.

Pulmonary arterial anastomotic stenosis is an unusual complication after single-lung transplantation. Intravascular ultrasound, performed at the bedside with an introducer sheath and guidewire, is a new technique that provides high-resolution tomographic images of the anastomotic site. This modality was used early in the postoperative course of a 58-year-old man to exclude significant pulmonary arterial anastomotic narrowing after right single-lung transplantation for primary pulmonary hypertension.