An anti-CD11/CD18 monoclonal antibody in patients with acute myocardial infarction having percutaneous transluminal coronary angioplasty (the FESTIVAL study).

Maximal benefits of coronary reperfusion after acute myocardial infarction (AMI) with ST-segment elevation may be attenuated by neutrophil-mediated reperfusion injury. Inflammatory mediators released from potentially viable myocytes cause activation of neutrophils, which traverse the endothelium and enter the myocardium. This process involves interaction between the neutrophil-expressed CD11/CD18 and endothelial-expressed intercellular adhesion molecule-1 (ICAM-1). Preclinical studies have shown that monoclonal antibodies (MAb) to CD18 can limit infarct size and preserve left ventricular function. We sought to determine the initial clinical safety and tolerability of Hu23F2G (LeukArrest), a humanized MAb to CD11/CD18, in patients with AMI who underwent percutaneous transluminal coronary angioplasty (PTCA). Sixty patients with AMI were randomized to low- (0.3 mg/kg) or high-dose (1.0 mg/kg) Hu23F2G or to placebo immediately before PTCA. We found no clinically significant differences in vital signs, physical examination, laboratory evaluation, or need for subsequent cardiac interventions. In Hu23F2G treatment groups, serum concentration of Hu23F2G increased rapidly to 3,234 +/- 1,298 microg/L (low-dose group) and 15,558 +/- 4409 microg/L (high-dose group) between 5 and 60 minutes, then declined over 72 hours to near-baseline values. Myocardial single-photon emission computed tomographic imaging 120 to 260 hours after PTCA showed no statistically significant differences in final left ventricular defect size. Hu23F2G was well tolerated, with no increase in adverse events, including infections. Thus, Hu23F2G appears safe and well tolerated in patients undergoing PTCA for AMI.

Coronary vasomotor reactivity among normotensive African and white American subjects with chest pain.

BACKGROUND AND OBJECTIVES: Excess cardiovascular morbidity and mortality among African (black) Americans is the subject of intensive investigation but the etiology remains speculative. One hypothesis proposes that inherent, or intrinsic, differences in coronary vascular reactivity and endothelial function predispose African Americans to enhanced vasoconstriction and/or depressed vasodilation, resulting in excess ischemia. The objective of this study was to establish whether coronary vasoreactivity differs among normotensive, nondiabetic African and white Americans with normal arteries referred for coronary arteriography because of chest pain. PATIENTS AND METHODS: Eleven African American (8 female, 3 male) and 28 white American (9 female, 19 male) normotensive, euglycemic patients with normal coronary arteries were prospectively recruited for invasive testing of coronary artery and microvascular relaxation using the endothelium-dependent and -independent agents, acetylcholine and adenosine; a Doppler tipped intracoronary guidewire; and quantitative coronary angiography. RESULTS: The study cohort consisted of 17 women (44%) and 22 men (56%) with a mean age of 46 +/- 10 yrs. Of 8 African American women, 6 were premenopausal and 2 were postmenopausal on estrogen replacement therapy. Of 9 white American women, 2 were premenopausal, 1 was 46-year old with a previous history of hysterectomy without ovariectomy, 2 were postmenopausal on estrogen replacement therapy, 2 were perimenopausal and 44- and 54-year old, and 2 were postmenopausal without estrogen replacement therapy. In response to maximal infusion of acetylcholine, epicardial coronary arteries and resistance vessels dilated similarly in black and white subjects. Dose-response curves revealed no significant racial differences during submaximal graded infusion of acetylcholine. In response to peak effect of adenosine, there were no racial differences in dilation of the microcirculation. CONCLUSIONS: In the absence of hypertension, diabetes mellitus, and angiographic evidence of coronary artery disease, African American women demonstrate no evidence of intrinsic predisposition to enhanced coronary conduit vasoconstriction or depressed microcirculatory dilation in response to the endothelium-dependent and -independent vasodilator agonists-acetylcholine and adenosine-when compared with responses of similar white men and women. Because of low enrollment of black males, definitive conclusions cannot be drawn regarding this group.

Effect of African-American race and hypertensive left ventricular hypertrophy on coronary vascular reactivity and endothelial function.

Excess cardiovascular morbidity and mortality among African (black) Americans remains an important yet unexplained public health problem. One possible explanation proposes that intrinsic or acquired abnormalities in coronary vascular reactivity and endothelial function result in excess ischemia among black Americans. To examine this hypothesis, we subjected 80 individuals with normal coronary arteries to invasive testing of coronary artery and microvascular relaxation using intracoronary infusions of acetylcholine and adenosine, a Doppler tipped intracoronary guide wire, and quantitative coronary angiography. We measured the percent increase in coronary blood flow and epicardial diameter after graded infusion of intracoronary acetylcholine and in coronary blood flow after intracoronary adenosine in 31 normotensive subjects (10 black, 21 white) and 49 hypertensive subjects with left ventricular hypertrophy (25 black, 24 white). Categorical and multivariate analyses revealed that in response to intracoronary adenosine and acetylcholine, the depression in endothelium-independent and -dependent microvascular relaxation during peak agonist effect was largely related to the presence of chronic hypertension and left ventricular hypertrophy. Normotensive subjects demonstrated no intrinsic racial differences in conduit and resistance vessel vasoreactivity. In response to maximal infusion of acetylcholine, epicardial coronary arteries constricted similarly in black and white subjects with hypertensive left ventricular hypertrophy and dilated similarly in normotensive black and white subjects. Thus, our study shows that in a cohort of black and white subjects referred for coronary arteriography because of chest pain, African American race is not associated with excess intrinsic or acquired depression in coronary vascular relaxation during the peak effect of the endothelium-dependent and -independent agonists acetylcholine and adenosine, after adjustment for the presence of left ventricular hypertrophy.

Coronary vasomotor function in a normotensive, nondiabetic referral population with normal coronary arteriograms.

In a referral normal cardiac population, endothelium-independent coronary relaxation is nearly always normal, but endothelium-dependent relaxation may be depressed in a significant proportion of patients. Further study of the natural history of referral subjects with endothelial dysfunction is necessary to assess the potential cardiovascular risk of this finding in a presumed low-risk population.

Inflated balloon entrapped in a calcified coronary stenosis.

Balloon angioplasty in calcified coronary lesions may have a decreased success rate and an increased incidence of complications. Previous cases have been reported on the phenomena of catheter or wire entrapment, but this report highlights a new problem in association with a calcified stenoses. This case lead to the unusual problem of the inflated balloon being entrapped within the lesion while the distal portion of the balloon remained inflated even after balloon deflation.

Same-day angioplasty and diagnostic catheterization: safe and effective but riskier in unstable angina.

Percutaneous transluminal coronary angioplasty was performed at the time of the diagnostic catheterization in 188 patients (215 lesions) at a University Hospital in order to assess the efficacy of this approach and the potential role it should play in the evaluation and treatment of patients. Patients either presented for diagnostic catheterization for evaluation of stable coronary disease (79 patients) or for unstable or new onset anginal symptoms (109 patients). Lesions were graded as to whether they were simple or complex; and post angioplasty films were reviewed for success rate, and degree of revascularization. Patients who were referred for stable anginal symptoms had a slightly higher success rate (91%) compared to those who were referred for new onset or more unstable symptomatology (85%, p = ns). Additionally, lesions morphology was judged to be more complex in unstable patients, as 67% had complex lesions with the presence of thrombus or ulcerated plaque in 56% of these stenoses. Angioplasty success was high for simple lesions in all patients, but was most unfavorable for complex stenoses in patients who presented with unstable symptoms (81% success rate). In patients who presented with new onset or unstable symptoms multivessel disease was present in 69% and angioplasty was more often geared at dilating a culprit stenosis leaving only 49% of these patients with complete revascularization. On the other hand, in 76% of those patients who presented with stable angina complete revascularization was a common outcome. Length of hospital stay was considerably shorter at 2.9 +/- 0.8 days in those patients who presented with stable symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous on-line monitoring of left ventricular function with a new nonimaging detector:validation and clinical use in the evaluation of patients post angioplasty.

A new miniaturized nonimaging radionuclide detector (Cardioscint, Oxford, England) was evaluated for the continuous on-line assessment of left ventricular function. This cesium iodide probe can be placed on the patient's chest and can be interfaced to an IBM compatible personal computer conveniently placed at the patient's bedside. This system can provide a beat-to-beat or gated determination of left ventricular ejection fraction and ST segment analysis. In 28 patients this miniaturized probe was correlated against a high resolution gamma camera study. Over a wide range of ejection fraction (31% to 76%) in patients with and without regional wall motion abnormalities, the correlation between the Cardioscint detector and the gamma camera was excellent (r = 0.94, SEE +/- 2.1). This detector system has high temporal (10 msec) resolution, and comparison of peak filling rate (PFR) and time to peak filling (TPFR) also showed close agreement with the gamma camera (PFR, r = 0.94, SEE +/- 0.17; TPFR, r = 0.92, SEE +/- 6.8). In 18 patients on bed rest the long-term stability of this system for measuring ejection fraction and ST segments was verified. During the monitoring period (108 +/- 28 minutes) only minor changes in ejection fraction occurred (coefficient of variation 0.035 +/- 0.016) and ST segment analysis showed no significant change from baseline. To determine whether continuous on-line measurement of ejection fraction would be useful after coronary angioplasty, 12 patients who had undergone a successful procedure were evaluated for 280 +/- 35 minutes with the Cardioscint system.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic response to OKT3 in orthotopic heart transplant recipients: evidence for reversible myocardial dysfunction.

The murine-derived monoclonal antibody OKT3 has been shown to be a useful immunosuppressive agent in transplant recipients; but it may cause cardiac instability and hemodynamic findings similar to those seen in septic shock after a first dose. Eight patients who received orthotopic heart transplants and were randomized to OKT3 therapy for immunosuppression were evaluated with serial hemodynamic and radionuclide monitoring for an 8-hour period during the first dose of OKT3. Cytokines including tumor necrosis factor-alpha, interleukin-1 and -2, and interferon-gamma were measured hourly to determine the potential mechanism of action of OKT3. All patients tolerated OKT3, although most had symptoms--pyrexia, chills, dyspnea, nausea and vomiting, and fever--within an hour after the dose. All patients exhibited a biphasic hemodynamic response to the first dose of OKT3. The initial hemodynamic response was characterized by a hyperdynamic phase with involvement in cardiac function as measured by cardiac output and ejection fraction. Left ventricular ejection fraction increased from 68% +/- 10% to 79 +/- 11% and was accompanied by increases in right ventricular ejection fraction and increases in cardiac index from 2.1 +/- 1.1 to 3.8 +/- 1.3 L/min/m2. The increase in ejection fraction was accompanied by a significant decrease in systemic vascular resistance index, from 2190 +/- 740 to 1608 +/- 573 dyne.sec.cm-5. The improvement in left ventricular ejection was caused by a significant decrease in end-systolic volume index (18 +/- 9.5 to 11 +/- 7 ml/m2). This occurred within the first 2 hours after OKT3 and was followed by cardiac index and ejection fraction returning to baseline in the next 2 to 3 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Cortical blindness after coronary angiography: a rare but reversible complication.

Transient cortical blindness is a recognized complication after vertebral and cerebral angiography but is a rare event after cardiac angiography. The development of cortical blindness appears to be an adverse reaction to the contrast agent which results in an osmotic disruption of the blood-brain barrier which appears to be selective for the occipital cortex. Patient outcome appears to be generally favorable with return of vision within 24-48 hr. This study describes three patients who had transient cortical blindness after cardiac catheterization and reviews what is known about this unusual problem.

Comparison of ambulatory left ventricular ejection fraction and blood pressure in systemic hypertension in patients with and without increased left ventricular mass.

To evaluate the effects of long-standing systemic hypertension on left ventricular (LV) function during daily activities, ambulatory radionuclide monitoring of LV ejection fraction (EF) and blood pressure was performed during exercise and other structured activities in 31 hypertensive patients. Patients were divided into 3 groups based on the absence of LV hypertrophy (group 1 [n = 16], LV mass 107 +/- 12 g/m2), presence of LV hypertrophy without electrocardiographic changes (group 2 [n = 10], LV mass 141 +/- 8 g/m2) and LV hypertrophy with associated electrocardiographic changes (group 3 [n = 5], LV mass 158 +/- 9 g/m2). The groups were similar with respect to age, baseline medication, treated and untreated blood pressure, resting EF and treadmill exercise time. Patients in group 3 had the longest history of hypertension. Peak filling rate was normal in group 1 (2.9 +/- 0.4 end-diastolic volume/s), but reduced at rest in groups 2 (2.4 +/- 0.4) and 3 (2.1 +/- 0.3). Patients in group 1 had normal EF responses to exercise and mental stress testing, as well as during routine ambulatory activities. Patients in group 2 had a blunted EF response to exercise, and those in group 3 had a significantly abnormal response. Both group 2 and 3 patients demonstrated abnormal EF responses to mental stress, as well as cold pressor testing in association with significant increases in mean arterial pressure and marked reduction in diastolic filling rate. Decreases in EF were also observed during routine patient monitoring in 3 group 3 patients and 4 group 2 patients. These events were associated with significantly increased blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of femoral artery guiding catheters via the left brachial artery for transluminal coronary angioplasty.

Percutaneous transluminal coronary angioplasty using the right brachial artery has been described using either a cutdown and arteriotomy or a percutaneous entry. Each method requires the use of a brachial artery guiding catheter (Stertzer guiding catheter; (USCI). This communication reports the use of percutaneous entry of the left brachial artery and coronary angioplasty performed with femoral guiding catheters. In this manner coronary angioplasty has been successfully performed in 42 of 47 patients (90%) without major complications.

Acute myocardial dysfunction and recovery: a common occurrence after coronary bypass surgery.

To evaluate whether acute myocardial dysfunction was common in the early postoperative period, serial hemodynamic measurements and radionuclide evaluation of ventricular function were performed before and after operation in 24 patients undergoing elective coronary bypass surgery. All patients had uncomplicated surgery, and no patient sustained an intraoperative infarction. In 96% of patients, significant depression in right and left ventricular ejection fraction was seen postoperatively, reaching a nadir at 262 +/- 116 min after coronary bypass. Left ventricular ejection fraction was 58 +/- 12% preoperatively and 37 +/- 10% at trough. Right ventricular function displayed a similar pattern. These findings were also associated with depressed cardiac and left ventricular stroke work index despite maintenance of adequate ventricular filling pressures and mean arterial pressure. The depression in ventricular function was partially reversible within 8 to 10 h after surgery. Left ventricular ejection fraction had increased to 55 +/- 13% at 426 +/- 77 min after coronary bypass and showed complete recovery within 48 h. Left ventricular end-systolic and end-diastolic volume index increased significantly postoperatively, but recovery in left ventricular ejection fraction was mostly due to decreases in end-systolic volume index (50 +/- 22 ml at trough and 32 +/- 16 ml at recovery). Depressed myocardial function was independent of bypass time, number of grafts placed, preoperative medications or core temperatures postoperatively. Postoperative therapy with pressors or inotropic agents delayed but did not prevent the occurrence of postoperative ventricular dysfunction. Despite improvements in operative techniques and methods of myocardial protection, postoperative left ventricular dysfunction continues to be common in patients undergoing cardiopulmonary bypass surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Stress thallium-201 imaging after coronary angioplasty predicts restenosis and recurrent symptoms.

The predictive accuracy of thallium imaging for the diagnosis of restenosis after angioplasty was evaluated in 121 patients who had undergone a successful procedure. Patients were evaluated three times over a 1 year follow-up period for symptoms, electrocardiographic (ECG) changes during exercise and the presence of reversible ischemia on exercise thallium imaging. At initial evaluation (4 to 6 weeks after angioplasty), 104 patients (86%) were asymptomatic. Of the 17 patients with chest pain symptoms, 9 had reversible ischemia on thallium imaging and all had restenosis. Of the 104 asymptomatic patients, 26 (25%) had a positive thallium scan (reversible ischemia) and this sign identified a high risk group. Evidence of restenosis was present by 6 months in 22 (85%) and by 1 year in 25 (96%) of these 26 patients. The largest group of patients manifested symptoms by the second evaluation (between 3 and 6 months after angioplasty). Of 28 patients with symptoms and a positive thallium scan at this evaluation, 26 had restenosis; on initial evaluation, 22 of these 26 patients had no symptoms but had had a positive thallium study. Ten of the 65 patients in the asymptomatic group had a positive thallium scan, but the scans of this group were not as predictive for recurrent symptoms as were those of the same group at initial evaluation. The 74 patients who had a negative thallium scan at 3 to 6 months with or without associated symptoms had a low likelihood of developing restenosis or symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of ambulatory radionuclide monitoring of left ventricular function early after acute myocardial infarction for predicting residual myocardial ischemia.

Ambulatory radionuclide monitoring of left ventricular function was performed with the nuclear Vest device in 35 patients early after acute myocardial infarction. Patients were evaluated during post-infarction treadmill, other activities that included mental stress and cold pressor challenge, and with stress thallium imaging and cardiac catheterization. Of the 35 patients evaluated, 14 had ischemic responses on treadmill testing and 21 had negative responses. By contrast, 20 had redistribution by thallium imaging suggesting ischemia. Vest studies demonstrated 56 responses suggestive of ischemia in 23 patients. Twenty-two occurred during exercise and 13 with mental stress. Seventy-five percent were silent and only 39% had associated electrocardiographic changes. Vest responses were compared in patients whose thallium scan was indicative of ischemia (thallium-positive) and those without ischemia (thallium-negative). Ejection fraction was higher in the thallium-positive group (0.52 +/- 0.11), as compared with thallium-negative patients (0.44 +/- 0.1). With exercise, ejection fraction decreased for the thallium-positive patients from 0.52 +/- 0.11 to 0.40 +/- 0.09 at peak exercise. For thallium-negative patients, ejection fraction changes were not significant. During mental stress, ejection fraction decreased from 0.51 +/- 0.11 to 0.45 +/- 0.12 for thallium-positive patients while thallium-negative patients were unchanged. Vest-measured decreases in ejection fraction of greater than or equal to 5 units during exercise were highly sensitive (90%), specific (73%) and predictive (82%) of a positive thallium scan. The same response for mental stress was specific (87%) and predictive (85%) of a positive scan result.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparable effects of intravenous nitroglycerin and intravenous nitroprusside in acute ischemia.

Forty patients with unstable angina were randomized to therapy with intravenous nitroglycerin (NTG) or nitroprusside (NTP). Invasive hemodynamic measurements were compared in both treatment groups and were used in concert with serial radionuclide monitoring of left ventricular function as patients were titrated to a therapeutic dose. Of the 22 patients randomized to intravenous NTG, there were 18 responders. Cardiac output significantly increased 28%, from 5.0 to 6.5 L/min at maximum effect. Mean pulmonary capillary wedge pressure (PCWP) decreased from 19 to 12 mm Hg. Mean arterial pressure decreased 10% and heart rate was unchanged (82 beats/min pre-treatment, 81 beats/min post-treatment). Radionuclide determined ejection fraction (EF) increased an average of 0.13, from 0.45 to 0.58. Peak filling rate paralleled increases in EF, increasing from 2.2 to 3.4 EDV/sec at peak level. Hemodynamic and radionuclide responses in the intravenous NTP group were compared to those with NTG. Of 18 patients randomized to NTP, 15 responders increased cardiac output from 5.1 to 6.8 L/min, a 35% increase. PCWP was 18 mm Hg at baseline and 10 mm Hg at peak effect. Mean arterial pressure decreased 13%, which was not significantly different from the NTG group. Heart rate response was identical to that in the NTG group. Ejection fraction increased an average of 0.17, from 0.43 to 0.60. Similar improvements were seen in peak filling rate (2.09 to 3.3 EDV/sec). There were no baseline differences between the NTG and NTP groups. In these patients NTG and NTP demonstrated equal efficacy, with the majority of patients showing substantial improvement in acute hemodynamics and left ventricular function with either agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic effects of intravenous metoprolol in acute myocardial infarction: the role of anatomic subsets in predicting patient response.

The acute effects of intravenous metoprolol were evaluated in 30 patients with myocardial infarction by means of serial hemodynamic and radionuclide measurements of left ventricular function. Within 1 hour of completion of the metoprolol dosing, 90% of the patients underwent cardiac catheterization to define anatomy and to assess patients for interventional therapy; the remainder had catheterization by 72 hours. All patients tolerated intravenous metoprolol without significant side effects. Patient responses to therapy were divided into two groups based on the angiographic findings. At catheterization, all group 1 patients had visible collaterals to or a patent vessel supplying the vascular distribution of the infarction. All group 2 patients had occluded coronary arteries without evidence of collaterals to the infarct zone. Group 1 (n = 13) improved both systolic and diastolic left ventricular function (mean ejection fraction [EF] = 46% to 55%, peak filling rate [PFR] = 2.1 to 3.2 Edv/sec), while group 2 (n = 17) patients were unchanged (EF = 43% to 42%, PFR = 2.0 to 1.9). Patient characteristics and time to treatment were similar in both groups, as were the hemodynamic effects of metoprolol. Heart rate decreased 20% in group 1 and 22% in group 2 and cardiac output fell 22% in group 1 and 32% in group 2. Acute improvement in ventricular function in these patients appears to be closely related to the coronary anatomy, and in those with flow to the infarct zone, intravenous metoprolol may be effective in preserving left ventricular function.

Incomplete revascularization in multivessel percutaneous transluminal coronary angioplasty: the role for stress thallium-201 imaging.

Evaluation of patients with multivessel coronary disease for percutaneous transluminal coronary angioplasty raises the question: Is incomplete revascularization an acceptable procedure in these patients, or does complete revascularization need to be performed, as in coronary artery bypass grafting? To provide an answer the present study utilized exercise thallium imaging as a guide to the performance of angioplasty in 85 patients with multivessel coronary disease. Preangioplasty exercise thallium imaging helped to identify the primary stenosis ("culprit lesion") in 93% of patients. Two weeks to 1 month after dilation of this lesion, repeat thallium imaging identified two patient groups: Group 1, 47 patients with no evidence of ischemia in a second vascular distribution and Group 2, 38 patients with evidence of further angioplasty. In Group 2 47% of patients had angioplasty of a second vessel and 79% required multivessel angioplasty at 1 year follow-up. In contrast, only six Group 1 patients (13%) required angioplasty of a second vessel at 1 year. Thus, incomplete revascularization may be an acceptable approach in many patients with multivessel coronary disease. Stress thallium-201 imaging may be a useful technique in the evaluation and management of these patients.

Usefulness of serial radionuclide monitoring during graded nitroglycerin infusion for unstable angina pectoris for determining left ventricular function and individualized therapeutic dose.

Using serial invasive hemodynamics in concert with noninvasive radionuclide monitoring of left ventricular (LV) function, 20 patients with unstable angina were evaluated during incremental infusion of intravenous nitroglycerin. Of 20 patients, 17 demonstrated a favorable hemodynamic response and dose responses could be determined for individual patients. There was excellent agreement between hemodynamic and noninvasive radionuclide measurements, and patient responses could be inferred from the radionuclide data alone. Cardiac output improved by 29% (mean 4.7 +/- 1.2 to 6.0 +/- 1.3), LV ejection fraction increased an average of 0.11 (0.39 +/- 0.14 to 0.50 +/- 0.16) and diastolic function as assessed by peak filling rate improved from 1.80 +/- 0.60 end-diastolic volumes/s to 2.70 +/- 0.90. Changes in systolic blood pressure and heart rate were not predictive of hemodynamic response. The dose of nitroglycerin necessary to produce maximal hemodynamic benefit was variable (mean 98 micrograms/min, range 48 to 144). In 7 patients, nitroglycerin caused excessive decreases in pulmonary arterial wedge pressure and adverse hemodynamics that corrected with intravenous fluids, allowing continued administration of intravenous nitroglycerin with improvement in hemodynamic status. In 15 patients, peak systolic pressure--end-systolic volume relations were assessed to define possible changes in LV contractility induced during nitroglycerin infusion. In 12 of these patients, this relation was linear, suggesting altered loading rather than augmented contractility as nitroglycerin's mechanism of action. In 3 patients a downward and rightward shift of the systolic relation was seen, suggesting that significant underloading with nitroglycerin was associated with depressed contractility.