Evidence for a direct stimulatory effect of prostacyclin on renin release in man.

THE OBJECTIVES OF THIS INVESTIGATION WERE: (a) to characterize the time and dose dependence of the effects of prostacyclin (PGI(2)) on renin release in healthy men; (b) to define whether PGI(2)-induced renin release is secondary to hemodynamic changes; (c) to determine the plasma and urine concentrations of 6-keto-PGF(1alpha) (the stable breakdown product of PGI(2)) associated with renin release induced by exogenous or pharmacologically enhanced endogenous PGI(2). Intravenous PGI(2) or 6-keto-PGF(1alpha) infusions at nominal rates of 2.5, 5.0, 10.0, and 20.0 ng/kg per min were performed in each of six normal human subjects; in three of them, PGI(2) infusion was repeated after beta-adrenergic blockade and cyclooxygenase inhibition. PGI(2), but not 6-keto-PGF(1alpha), caused a time- and dose-dependent increase of plasma renin activity, which reached statistical significance at 5.0 ng/kg per min and was still significantly elevated 30 min after discontinuing the infusion. Although combined propranolol and indomethacin treatment significantly enhanced the hypotensive effects of infused PGI(2), it did not modify the dose-related pattern of PGI(2)-induced renin release. Plasma 6-keto-PGF(1alpha) levels rose from undetectable levels (<7.5 pg/ml) in a stepwise fashion during increasingly higher infusion rates of PGI(2) or 6-keto-PGF(1alpha). The threshold concentration of plasma 6-keto-PGF(1alpha) associated with a statistically significant stimulation of renin release was approximately 200 pg/ml. Upon discontinuing PGI(2) or 6-keto-PGF(1alpha) infusion, the disappearance of 6-keto-PGF(1alpha) from blood showed an identical biphasic behavior, the initial phase having an apparent t((1/2)) of 3.2 min. The intravenous infusion of furosemide, which is known to stimulate renin release via a cyclooxygenase-dependent mechanism, caused a three-to fourfold increase of urinary 6-keto-PGF(1alpha) excretion rate, concomitant with the elevation of plasma renin activity levels, in six healthy women. 6-Keto-PGF(1alpha) remained undetectable in peripheral venous plasma throughout the study. WE CONCLUDE THAT IN HUMAN SUBJECTS: (a) PGI(2)-induced renin release occurs with a dose and time dependence similar to its reported platelet effects; (b) PGI(2)-induced renin release is not mediated by adrenergic stimuli or cyclooxygenase-dependent mechanisms secondary to hemodynamic changes; (c) furosemide-induced renin release is associated with increased renal PGI(2) formation; and (d) PGI(2) appears to act as a local modulator rather than a circulating hormone in controlling juxtaglomerular function.

Enoximone echocardiography for predicting recovery of left ventricular dysfunction after revascularization : a novel test for detecting myocardial viability.

BACKGROUND: The possibility that enoximone, a nonglycoside, noncatechol, positive inotropic agent, in combination with 2-dimensional echocardiography may predict recovery of myocardial dysfunction after revascularization has not been yet evaluated. METHODS AND RESULTS: Forty-five patients with chronic coronary artery disease and left ventricular dysfunction underwent dobutamine (DE, 5 to 10 microg. kg(-1). min(-1)) and enoximone (EE, 1.5 mg/kg, over 10 minutes) echocardiography. Myocardial wall motion was scored from 1 (normal) to 4 (dyskinesia): an asynergic segment was considered to have contractile enhancement when the score decreased by >/=1 grade. Of 478 asynergic segments, 216 (45%) exhibited functional recovery after revascularization. Dobutamine- and enoximone-induced contractile enhancement was observed in 41% and 46% of segments, respectively. Compared with DE, EE had higher sensitivity (88% versus 79%, P<0.01) and negative predictive value (90% versus 84%, P<0.05) in predicting functional recovery. The specificity (89% versus 90%) and positive predictive value (87% for both EE and DE) were similar. Concordant interpretation of EE and DE findings was found in 85% (406 of 478) of affected segments. Prerevascularization coronary angiography showed that stenosis severity of vessels supplying areas which only improved with enoximone was significantly greater (89.9%) than that of vessels (77.7%) supplying areas that responded to both agents (P<0.02). Both dobutamine and enoximone increased heart rate (16% and 10%, respectively), whereas enoximone did not cause changes in systolic blood pressure that increased by 14% with dobutamine. CONCLUSIONS: Enoximone echocardiography provides a novel and reliable approach for the prediction of functional recovery after revascularization. Compared with dobutamine echocardiography, the test yields higher sensitivity and induces lesser hemodynamic alterations.

Circumferential radiofrequency ablation of pulmonary vein ostia: A new anatomic approach for curing atrial fibrillation.

BACKGROUND: The pulmonary veins (PVs) and surrounding ostial areas frequently house focal triggers or reentrant circuits critical to the genesis of atrial fibrillation (AF). We developed an anatomic approach aimed at isolating each PV from the left atrium (LA) by circumferential radiofrequency (RF) lesions around their ostia. METHODS AND RESULTS: We selected 26 patients with resistant AF, either paroxysmal (n=14) or permanent (n=12). A nonfluoroscopic mapping system was used to generate 3D electroanatomic LA maps and deliver RF energy. Two maps were acquired during coronary sinus and right atrial pacing to validate the lateral and septal PV lesions, respectively. Patients were followed up closely for >/=6 months. Procedures lasted 290+/-58 minutes, including 80+/-22 minutes for acquisition of all maps, and 118+/-16 RF pulses were deployed. Among 14 patients in AF at the beginning of the procedure, 64% had sinus rhythm restoration during ablation. PV isolation was demonstrated in 76% of 104 PVs treated by low peak-to-peak electrogram amplitude (0. 08+/-0.02 mV) inside the circular line and by disparity in activation times (58+/-11 ms) across the lesion. After 9+/-3 months, 22 patients (85%) were AF-free, including 62% not taking and 23% taking antiarrhythmic drugs, with no difference (P:=NS) between paroxysmal and permanent AF. No thromboembolic events or PV stenoses were observed by transesophageal echocardiography. CONCLUSIONS: Radiofrequency PV isolation with electroanatomic guidance is safe and effective in either paroxysmal or permanent AF.

Catheter ablation of paroxysmal atrial fibrillation using a 3D mapping system.

BACKGROUND: We treated paroxysmal recurrent atrial fibrillation (AF) with radiofrequency (RF) catheter ablation by creating long linear lesions in the atria. To achieve line continuity, a 3D electroanatomic nonfluoroscopic mapping system was used. METHODS AND RESULTS: In 27 patients with recurrent AF, a catheter incorporating a passive magnetic field sensor was navigated in both atria to construct a 3D activation map. RF energy was delivered to create continuous linear lesions: 3 lines (intercaval, isthmic, and anteroseptal) in the right atrium and a long line encircling the pulmonary veins in the left atrium. After RF application, the atria were remapped to validate completeness of the block lines, demonstrated by late activation of the areas circumscribed by the lines. The mean procedure duration was 312+/-103 minutes (range, 187 to 495), with mean fluoroscopy time of 107+/-44 minutes (range, 32 to 185 minutes). No acute complications occurred, but 1 patient experienced early prolonged sinus pauses and received a pacemaker. During the first day, 17 patients (63%) had AF episodes, but at discharge, 25 patients were in sinus rhythm. After a follow-up of 6. 0 to 15.3 months (average, 10.5+/-3.0 months), 16 patients are asymptomatic, 3 have an almost complete disappearance of symptoms, 1 patient is improved, and 7 patients have their AF attacks unchanged. CONCLUSIONS: Paroxysmal recurrent drug-refractory AF can be treated by RF catheter ablation. Creation of long continuous linear lesions necessary to compartmentalize the atria is facilitated by a nonfluoroscopic electroanatomic mapping system.

Impairment of myocardial perfusion and function during painless myocardial ischemia.

Left ventricular (or pulmonary and systemic arterial) hemodynamics were measured for a mean of 13.6 hours during continuous electrocardiographic monitoring in 14 patients admitted to the coronary care unit because of angina at rest. Of 293 episodes of transient ST segment and T wave changes identified, 247 (84%) were completely asymptomatic. Sixty-three percent of asymptomatic episodes were associated with an elevation of the left ventricular end-diastolic or pulmonary artery diastolic pressure of 5 mm Hg or more; in 15% there were smaller elevations (2 to 4 mm Hg) and in 22% there were no changes or less than a 2 mm Hg elevation of pressure. The peak contraction and relaxation dP/dt (first derivative of left ventricular pressure) were reduced to 100 mm Hg/s or more in 84 and 81% of asymptomatic episodes, respectively. Great cardiac vein oxygen saturation measured in three patients showed an increased myocardial oxygen extraction similar to that seen in painful episodes, which preceded and accompanied asymptomatic electrocardiographic changes. These results indicate that asymptomatic electrocardiographic changes represent transient myocardial ischemia. Comparison of asymptomatic and symptomatic episodes revealed that asymptomatic episodes were generally shorter (253 +/- 159 versus 674 +/- 396 seconds, probability [p] less than 0.001) and produced less impairment of left ventricular function: there were smaller elevations of left ventricular end-diastolic or pulmonary artery diastolic pressure (5.9 +/- 5.0 versus 16.5 +/- 6.9 mm Hg, p less than 0.001), and smaller reductions of peak left ventricular contraction dP/dt (252 +/- 156 versus 395 +/- 199 mm Hg/s, p less than 0.001) and relaxation dP/dt (259 +/- 191 versus 413 +/- 209 mm Hg/s, p less than 0.001). In individual patients, however, asymptomatic and symptomatic episodes of similar duration and severity were observed. The duration and severity of ischemia appear important for the genesis of anginal pain, but additional factors must be involved.

Transdermal nitroglycerin reduces the frequency of anginal attacks but fails to prevent silent ischemia.

OBJECTIVES: The aim of this study was to objectively evaluate the effects of intermittent administration of transdermal nitroglycerin on effort tolerance, frequency of anginal attacks and presence of silent ischemic events that occur during normal daily activities. BACKGROUND: Previous studies have shown that transdermal nitroglycerin patches reduce the incidence of anginal attacks and improve exercise capacity when given intermittently. However, no carefully controlled studies are available on the effects of these preparations (and their dosing schedule) on the occurrence of "silent" ischemic events during unrestricted daily activities. METHODS: Twelve men with chronic stable angina, a positive exercise test result and significant coronary artery disease completed a randomized, double-blind, placebo-controlled trial in which patches were worn either continuously or with overnight (8 h) removal. The effects of treatment were objectively assessed by both treadmill exercise testing and 24-h ambulatory electrocardiographic monitoring. RESULTS: Only the intermittent dosing schedule afforded a small but significant improvement in exercise tolerance and prolonged exercise duration and time to ST segment depression. The frequency of anginal attacks was also reduced by both the continuous and intermittent treatment, but the effects on symptoms were not paralleled by a concomitant reduction in ischemic episodes recorded during ambulatory monitoring. CONCLUSIONS: The results indicate that when used as monotherapy, intermittent transdermal nitroglycerin preparations lessen symptoms but are ineffective for the long-term prophylaxis of silent myocardial ischemia.

Coronary recanalization by elective angioplasty prevents ventricular dilation after anterior myocardial infarction.

OBJECTIVES: In a prospective study we evaluated whether late recanalization of the left anterior descending coronary artery (LAD) affects ventricular volume and function after anterior myocardial infarction. BACKGROUND: Persistent coronary occlusion after anterior myocardial infarction leads to ventricular dilation and heart failure. METHODS: We studied 73 consecutive patients with acute anterior myocardial infarction as a first cardiac event; all had an isolated lesion or occlusion of the proximal LAD. Six patients died before hospital discharge. The 67 survivors were classified into two groups: group I (patent LAD and good distal flow, n = 40) and group II (LAD occlusion or subocclusion, n = 27). The 20 patients in group I who had significant residual stenosis and all patients in group II underwent elective percutaneous transluminal coronary angioplasty (PTCA) within 18 days of myocardial infarction. The procedure was successful in 17 patients in group I (group IB) and in 16 patients in group II (group IIA): in the remaining 11 patients of group II, patency could not be reestablished (group IIB). Left ventricular volumes, ejection fraction and a dysfunction score were measured by echocardiography on admission, before PTCA, at discharge and after 3 and 6 months. RESULTS: Although cumulative ST segment elevation was similar in groups I and II, ejection fraction and dysfunction score were significantly worse in group II. However, ventricular function and volumes progressively improved in group IIA, whereas group IIB exhibited progressive deterioration of function (dysfunction score [mean +/- SD] increased from 21 +/- 6 to 25 +/- 8, p < 0.05; ejection fraction decreased from 43 +/- 10% to 37 +/- 11%, p < 0.05); and end-systolic volume increased from 34 +/- 10 to 72 +/- 28 ml/m2, p < 0.05). Patients in group IIB also had worse effort tolerance, higher heart rate at rest, lower blood pressure and significantly greater prevalence of chronic heart failure. CONCLUSIONS: Delayed PTCA of an occluded LAD can frequently restore vessel patency. Success appears to be associated with better ventricular function and a lack of chronic dilation. Large randomized studies are warranted to evaluate the effect of delayed PTCA on late mortality.

Computer system for analysis of ST segment changes on 24 hour Holter monitor tapes: comparison with other available systems.

The accuracy of a computer system that was developed for the analysis of ST segment changes recorded on Holter ambulatory electrocardiographic monitoring tapes was compared with conventional visual scrutiny, beat by beat analog printouts and a commercial J point trend system. The program calculates and plots multiple electrocardiographically derived variables in a high temporal resolution trend format. Fifty tapes of good recording quality obtained from 19 patients (13 with chronic stable angina and 6 with variant angina) were assessed visually and with the computer system; of these, 20 were analyzed by all four techniques. In the 50 tapes, 629 episodes of diagnostic ST segment changes (all true positive results) were identified by using the computer system. In contrast, only 507 were identified by visual scrutiny; none of these 507 episodes was missed by computer analysis. On the 20 tapes assessed using computer, visual, beat by beat analog and J point trend system analysis, 268, 221, 230 and 178 episodes, respectively, were documented. For the four techniques, false negative and positive results were 0, 47, 38 and 90 and 0, 10, 6 and 24, respectively. The results indicate that, of the systems assessed in this study, the computer program provides the highest accuracy for detection of transient ST segment changes. This is probably accreditable to the compact presentation of multiple electrocardiographically derived variables, allowing a detailed quantitative assessment of 24 hour tapes. It is of particular value for pathophysiologic and pharmacologic studies.

Assessment of residual tissue viability by exercise testing in recent myocardial infarction: comparison of the electrocardiogram and myocardial perfusion scintigraphy.

The assessment of residual myocardial viability in infarcted areas is relevant for subsequent management and prognosis but requires expensive technology. To evaluate the possibility that simple, easily obtainable clinical markers may detect the presence of within-infarct viable tissue, the significance of exercise-induced ST elevation occurring in leads exploring the area of a recent Q wave myocardial infarction was assessed. Twenty-five patients with recent (less than 6 months) myocardial infarction were studied. All had angiographically documented coronary artery disease, diagnostic Q waves (n = 24) or negative T waves (n = 25) on the rest 12-lead electrocardiogram and exhibited during exercise greater than or equal to 1.5 mm ST segment elevation (n = 17) or isolated T wave pseudonormalization (n = 8) in the infarct-related leads. ST-T wave changes were reproduced in all patients during thallium-201 exercise myocardial scintigraphy. A fixed perfusion defect was observed in 24 of the 25 patients. A reversible defect was seen in 16 (94%) of 17 patients who exhibited transient ST elevation during exercise but in only 4 (50%) of the 8 patients who had only T wave pseudonormalization. In conclusion, in patients with recent myocardial infarction, analysis of simple ST segment variables obtained during exercise testing may allow a first-line discrimination of those who may potentially benefit from a revascularization procedure.

Comparison of stress/rest myocardial perfusion tomography, dipyridamole and dobutamine stress echocardiography for the detection of coronary disease in hypertensive patients with chest pain and positive exercise test.

OBJECTIVES: Although different noninvasive tests have been proposed for detecting coronary artery disease (CAD) in patients with hypertension and chest pain symptoms, the relative performance of the available techniques has not been systematically assessed. BACKGROUND: Patients with hypertension frequently complain of chest pain and exhibit ischemic-like ST segment changes on the exercise electrocardiogram (ECG). However, the specificity of such changes for predicting significant CAD is very low, because these patients often exhibit a normal coronary angiogram. METHODS: In 101 patients with hypertension, chest pain and positive exercise ECG, we performed stress/rest myocardial single photon emission computed tomography with 99mTc-MIBI, dipyridamole and dobutamine stress echocardiography and coronary angiography. All patients had normal global ventricular function and 57 had left ventricular hypertrophy. All were kept on ACE inhibitors during the study period. RESULTS: No patients had significant side effects during perfusion scintigraphy. Dose-limiting side effects were observed in five patients with dipyridamole and in seven patients with dobutamine. Only 56% of study patients exhibited significant CAD. Sensitivity, specificity, accuracy, positive and negative predictive values were, respectively, 98%, 36%, 71%, 67% and 94% for perfusion scintigraphy, 61%, 91%, 74%, 90% and 64% for dipyridamole and 88%, 80%, 84%, 85% and 83% for dobutamine stress echocardiography. CONCLUSIONS: This study shows that stress echo in patients with hypertension yields a satisfactory diagnostic accuracy for identifying significant epicardial CAD. Our results indicate that dobutamine might be superior to dipyridamole. The low specificity of myocardial scintigraphy probably relates to the fact that this method traces perfusion abnormalities, not necessarily caused by epicardial CAD, possibly due to microvascular disease and not causing obvious wall motion abnormalities.

Short- and long-term evolution of unstented nonocclusive coronary dissection after coronary angioplasty.

OBJECTIVES: We assessed the short- and long-term clinical and angiographic outcome of nonocclusive unstented dissection after percutaneous transluminal coronary angioplasty (PTCA) and its correlation with restenosis. BACKGROUND: The use of stents has dramatically increased both the number and the cost of coronary revascularization procedures. However, this technique is not completely risk free, and its benefits have not been fully demonstrated in uncomplicated dissections. METHODS: We studied 129 consecutive patients with 49 nonocclusive dissections after PTCA (grades A to D of National Heart, Lung, and Blood Institute classification) and good distal flow (TIMI [Thrombolysis in Myocardial Infarction] flow grade 3). All patients underwent coronary angiography at 24 h and at six months post-PTCA. Clinical status was assessed every three months in the outpatient clinic. Study subjects were matched with 60 other patients in whom stenting was performed for the presence of dissection. RESULTS: In the former group, all but two patients (with type E dissection, which evolved to coronary occlusion and myocardial infarction) improved their dissection score during follow-up: at six months only 18 dissections were still angiographically visible, and no clinical adverse events were recorded. In the dissected vessels, the restenosis rate was significantly lower than in those without dissection (12% vs. 44%, p < 0.001); in the stented vessels, the restenosis rate was 25% (15/60). CONCLUSIONS: In the presence of TIMI flow grade 3, coronary dissection is associated with a favorable outcome and predicts a low restenosis rate. These results caution against the indiscriminate use of intravascular prostheses in the event of nonocclusive coronary dissection.

Symptom-limited exercise testing causes sustained diastolic dysfunction in patients with coronary disease and low effort tolerance.

Exercise stress testing is routinely used for the noninvasive assessment of coronary artery disease and is considered a safe procedure. However, the provocation of severe ischemia might potentially cause delayed recovery of myocardial function. To investigate the possibility that maximal exercise testing could induce prolonged impairment of left ventricular function, 15 patients with angiographically proved coronary disease and 9 age-matched control subjects with atypical chest pain and normal coronary arteries were studied. Radionuclide ventriculography was performed at rest, at peak exercise, during recovery and 2 and 7 days after exercise. Ejection fraction, peak filling and peak emptying rates and left ventricular wall motion were analyzed. All control subjects had a normal exercise test at maximal work loads and improved left ventricular function on exercise. Patients developed 1 mm ST depression at 217 +/- 161 s at a work load of 70 +/- 30 W and a rate-pressure product of 18,530 +/- 4,465 mm Hg x beats/min. Although exercise was discontinued when angina or equivalent symptoms occurred, in all patients diagnostic ST depression (greater than or equal to 1 mm) developed much earlier than symptoms. Predictably, at peak exercise patients showed a decrease in ejection fraction and peak emptying and filling rates. Ejection fraction and peak emptying rate normalized within the recovery period, whereas peak filling rate remained depressed throughout recovery (p less than 0.002) and was still reduced 2 days after exercise (p less than 0.02). In conclusion, in patients with severe impairement of coronary flow reserve, maximal exercise may cause sustained impairement of diastolic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Time course and determinants of left ventricular function recovery after primary angioplasty in patients with acute myocardial infarction.

OBJECTIVES: We sought to evaluate the importance of time in relation to treatment, time course and determinants of recovery of left ventricular (LV) function in patients with acute myocardial infarction (AMI) undergoing primary percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Myocardial salvage has been shown to be dependent on the time elapsed from the onset of AMI to reperfusion. METHODS: Left ventricular function was evaluated at hospital admission, after angioplasty, at 24 h and 6 months by both echocardiography and angiography and at 1, 7, 30, 90 and 180 days by echocardiography in 101 consecutive patients. RESULTS: Patients were allocated to three groups according to interval between symptom onset and angioplasty: <2 h (group A), 2 to 4 h (group B) and >4 h (group C). Patients in groups A and B showed a progressive improvement of LV function between day 7 and day 90, which became statistically significant at day 30 (p < 0.01). No LV function changes were noted in group C patients. Thrombolysis In Myocardial Infarction (TIMI) flow grade <3 at 24 h was not associated with any significant change in LV volume and function during the six-month follow-up period. Restenosis, when associated with TIMI flow grade 3 in the infarct-related vessel, did not influence LV function. Flow grade <3 of the infarct-related artery was not associated with any improvement of cardiac events independently from the time to treatment at the initial procedure. CONCLUSIONS: Patients undergoing primary PTCA for AMI have a good recovery of LV function if TIMI flow grade 3 is restored within 4 h. Coronary angioplasty limits further remodeling of the LV in patients treated after 4 h.

Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women.

OBJECTIVES: We sought to compare the effects of estrogen/transvaginal progesterone gel with estrogen/medroxyprogesterone acetate (MPA) on exercise-induced myocardial ischemia in postmenopausal women with coronary artery disease or previous myocardial infarction, or both. BACKGROUND: Estrogen therapy beneficially affects exercise-induced myocardial ischemia in postmenopausal women; however, women with an intact uterus also take progestin to protect against uterine malignancies. The effects of combination estrogen/progestin therapy on myocardial ischemia are unknown. METHODS: Eighteen postmenopausal women (mean +/- SD age 59+/-7 years) were given 17-beta-estradiol in single-blinded manner for four weeks (1 mg/day for three weeks then 2 mg/day for one week). Estradiol (2 mg/day) was then continued, and the patients were randomized (double-blind) for 12 days to either transvaginal progesterone gel (90 mg on alternate days) and oral MPA placebo (10 mg/day), or vice versa. After another two weeks on estradiol alone, the patients crossed over to progestin treatment and repeated the protocol on the opposite treatment. Patients underwent treadmill exercise testing after each estradiol phase and at day 10 of each progestin phase. RESULTS: Exercise time to myocardial ischemia increased after the first estrogen phase as compared with baseline (mean difference with 95% confidence interval [CI]: 72 s [34 to 110], p = 0.001), and was increased by combination estradiol/progesterone therapy as compared with estradiol/MPA therapy (92 s [35 to 149], p = 0.001)). Two patients (11%) were withdrawn while taking estradiol/MPA owing to unstable angina. CONCLUSIONS: Combination estrogen/transvaginal progesterone gel increases exercise time to myocardial ischemia, as compared with estrogen/MPA. These results imply that the choice of progestin in women at higher cardiovascular risk requires careful consideration.

Wiktor stent for treatment of chronic total coronary artery occlusions: short- and long-term clinical and angiographic results from a large multicenter experience.

OBJECTIVES: This study reports the first multicenter experience with the Wiktor coil stent for treatment of chronic total coronary artery occlusions (CTOs). BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) of CTO is associated with very high restenosis and reocclusion rates. Coronary stenting has been proposed as a means of improving outcome. However, the Wiktor device for CTOs has never been tested in a large patient sample. METHODS: From January 1993 to December 1996, 89 patients with 91 CTOs underwent Wiktor stent implantation after successful PTCA. The post-stenting regimen consisted of warfarin (Coumadin) plus aspirin in the initial 49 patients (55%) and aspirin plus ticlopidine in 40 patients (45%). RESULTS: Stenting was successful in 87 patients (98%). At 1 month, 6% of patients had subacute stent thrombosis, 3% had a major bleeding event, and 1% had access-site complications. Subacute stent thrombosis showed univariate association with warfarin therapy (p = 0.009). Angiographic follow-up was obtained in 76 (93%) of 82 eligible patients. The restenosis rate was 32%, including 4% reocclusions. By multiple logistic regression analysis, restenosis was independently associated with multiple stents (adjusted odds ratio [OR] 27.67, 95% confidence interval [CI] 4.25 to 79.95, p = 0.0008) and increasing values of occlusion length (adjusted OR 1.23, 95% CI 1.09 to 1.39, p = 0.001). Freedom from death, myocardial infarction or stented vessel revascularization was 87% and 72% at 1 and 3 years, respectively. CONCLUSIONS: Short- and long-term clinical and angiographic outcomes are favorable in patients undergoing Wiktor stent implantation in CTO. Further technical improvement is needed to reduce the restenosis rate in patients with long lesions and multiple stents.

Endothelial and metabolic characteristics of patients with angina and angiographically normal coronary arteries: comparison with subjects with insulin resistance syndrome and normal controls.

OBJECTIVES: This study was performed to characterize the endothelial and metabolic alterations of patients with angina and angiographically normal coronary arteries ("cardiac" syndrome X [CSX]) compared with subjects with insulin resistance syndrome ("metabolic" syndrome X [MSX]) and normal controls. BACKGROUND: Previous studies have found high endothelin-1 levels, impaired endothelium-dependent vasodilation and insulin resistance in patients with angina pectoris and angiographically normal coronary arteries. On the other hand, subjects with insulin resistance syndrome have shown high endothelin-1 levels. METHODS: Thirty-five subjects were studied: 13 patients with angina pectoris and angiographically normal coronary arteries (CSX group); 9 subjects with insulin resistance syndrome (MSX group) and 13 normal controls. All subjects received an acute intravenous bolus of insulin (0.1 U/kg) combined with a euglycemic clamp and forearm indirect calorimetry. Endothelin-1 levels, nitrite/nitrate (NOx) levels, end products of nitric oxide metabolism, glucose infusion rates (index of insulin sensitivity) and their incremental areas (deltaAUCs [area under curves]) were measured during this period. RESULTS: Basal endothelin-1 levels were higher in CSX and MSX groups than in normal controls (8.19 +/- 0.46 and 6.97 +/- 0.88 vs. 3.67 +/- 0.99 pg/ml; p < 0.01), while basal NOx levels were significantly higher in MSX group than in CSX and normal controls (36.5 +/- 4.0 vs. 24.2 +/- 3.3 and 26.8 +/- 3.2 mol/liter, p < 0.05). After insulin administration, the deltaAUCs of NOx (p < 0.05) were lower in CSX group than in MSX and normal controls, and the deltaAUCs of endothelin-1 were lower in group CSX than in normal controls. Glucose infusion rate was significantly lower in CSX and MSx groups than in normal controls (p < 0.01), suggesting that in both CSX and MSX groups insulin resistance is present. A positive correlation was found between the deltaAUCs of nitric oxide and the AUCs of glucose infusion rate. CONCLUSIONS: Blunted nitric oxide and endothelin responsiveness to intravenously infused insulin is a typical feature of patients with angina pectoris and angiographically normal coronary arteries and may contribute to the microvascular dysfunction observed in these subjects.

Exercise-induced ischemic arrhythmias in patients with previous myocardial infarction: role of perfusion and tissue viability.

OBJECTIVES: This study sought to investigate whether residual viability of infarcted myocardium may play a role in the pathogenesis of exercise-induced ventricular arrhythmias. BACKGROUND: We previously showed that transient ischemia within partially infarcted areas often precipitates ventricular arrhythmias during exercise that are consistently obliterated by intravenous nitrates. METHODS: We studied 60 patients with chronic stable angina and a previous myocardial infarction. All underwent at least two consecutive exercise stress tests, coronary angiography and stress/rest myocardial perfusion tomography by Tc-99m 2-methoxy isobutyl isonitrile (MIBI). In the last 26 consecutive patients, residual viability was assessed by single-photon emission computed tomography (SPECT) using fluorine (F)-18 fluorodeoxyglucose. Perfusion and metabolic data were evaluated qualitatively by three independent observers in blinded manner. RESULTS: With exercise, 30 patients (group A) consistently developed ventricular arrhythmias (> 10 ventricular ectopic beats/min, couplets, nonsustained ventricular tachycardia); the remaining 30 patients (group B) did not. The severity of coronary artery disease (Gensini score) was similar in the two groups. Postexercise SPECT showed partial reperfusion of an infarcted area in 28 of 30 patients of group A but in only 9 of 30 of group B (p < 0.0001). Uptake of F-18 fluorodeoxyglucose was observed within the infarcted zone in 10 of 13 and 1 of 13 patients in groups A and B, respectively (p = 0.0003). CONCLUSIONS: In patients with myocardial infarction, exercise-induced ventricular arrhythmias appear to be triggered by transient ischemia occurring within a partially necrotic area containing large amounts of viable myocardium. Therefore, occurrence of arrhythmias during exercise may represent a clue to the presence of residual viability within a previously infarcted area.

Specificity and sensitivity of exercise-induced ST segment elevation for detection of residual viability: comparison with fluorodeoxyglucose and positron emission tomography.

OBJECTIVES: We evaluated the sensitivity and specificity of exercise-induced ST segment elevation for the detection of residual myocardial viability. BACKGROUND: Assessment of residual viability after myocardial infarction is relevant for establishing indication for revascularization. We have previously shown that exercise-induced ST segment elevation is a marker of residual viability. METHODS: We studied 34 patients with a previous Q wave myocardial infarction (anterior in 21, inferior in 13) of whom 18 (group A) had exercise-induced ST segment elevation in more than one lead (mean [+/- SD] 1.8 +/- 0.9 mm, range 1 to 4) and 16 (group B) did not. All patients underwent rest technetium-99m methoxyisobutyl isonitrile single-photon emission computed tomography (SPECT), fluorine-18 (F-18) fluorodeoxyglucose positron emission tomography and coronary angiography. The time elapsed between the infarction and the viability study was 72 +/- 108 days (range 15 to 400) in group A and 516 +/- 545 days (range 14 to 1,800) in group B. RESULTS: The presence and site of previous infarction were confirmed by SPECT studies in all 34 patients. Uptake of F-18 fluorodeoxyglucose within the infarcted area was present in 18 of 18 patients in group A but in only 9 (56%) of 16 in group B (p < 0.01). In patients with an anterior infarction, the sensitivity, specificity and predictive accuracy of exercise-induced ST segment elevation for detection of residual viability were 82%, 100% and 86%, respectively (95% confidence intervals 46% to 83.5%, 59% to 100% and 55.6% to 87.1%, respectively). CONCLUSIONS: Exercise-induced ST segment elevation in infarct-related leads has a high specificity and acceptable sensitivity for detection of residual viability within the infarcted area.

Mechanisms of ischemic cardiac pain and silent myocardial ischemia.

The mechanisms of cardiac ischemic pain remain obscure. It is unknown whether ischemia causes cardiac pain by the release of chemical substances or by mechanical stretching. It is also unknown whether ischemia activates specific nociceptors and pain fibers or mechanoreceptors and chemoreceptors. In patients who have both painful and painless ischemic episodes, a certain minimal duration and severity of ischemia are necessary but insufficient to explain the presence of pain, since very severe ischemia of long duration can be silent. Thus, central transmission of painful stimuli and the pain perception threshold appear to play major roles in determining the presence or absence of pain. The emotional state and psychologic expectations of patients may affect their perception and threshold of pain considerably.

A single-blind, placebo-controlled study of effects of atenolol on transient ischemia in "mixed" angina.

The efficacy of atenolol in preventing episodes of transient ischemia during daily life was evaluated in 10 patients with "mixed" angina who underwent a 4-week, single-blind, double-crossover placebo-controlled trial. On day 6 and 7 of each treatment phase, continuous ambulatory electrocardiographic monitoring was performed for 48 hours. On day 7 an exercise test was also performed. Two-hundred and sixty-four ischemic episodes (79% "silent") were recorded during placebo treatment; 98 were recorded during atenolol treatment (63% decrease, p less than 0.01). In agreement with previous observations, most ischemic episodes observed during placebo (156 or 59%) were not preceded by an increase in heart rate. Surprisingly, the beneficial effects of atenolol were more pronounced for these episodes than for those preceded by an increase in heart rate and apparently caused by an increase in myocardial demand (decreases of 72% and 48%, respectively). Painful and painless episodes were decreased by a similar extent. In all patients, the heart rate recorded at the beginning of ST-segment depression was widely variable and significantly lower with atenolol (64 +/- 14 beats/min) than with placebo (81 +/- 13 beats/min, p less than 0.05). During both placebo and atenolol treatment, the highest incidence of ischemic events was observed between 6 A.M. and 9 P.M., in coincidence with the highest levels of the heart rate resting.(ABSTRACT TRUNCATED AT 250 WORDS)