Reduced distal embolization with transluminal extraction atherectomy compared to balloon angioplasty for saphenous vein graft disease.

Extraction atherectomy utilizes suction aspiration as an attempt to limit distal emboli during atherectomy. We sought to test the hypothesis that extraction atherectomy produces less distal embolization than balloon angioplasty when treating saphenous vein grafts. Among 163 consecutive, nonrandomized patients, 103 patients underwent transluminal extraction catheter (TEC) atherectomy with or without adjunctive balloon angioplasty, and 60 patients had conventional balloon angioplasty. Both groups showed comparably high procedural success rates (TEC 90.3%, angioplasty 83.3%, P = NS). TEC cases had a significantly lower incidence of angiographic distal embolization, compared with angioplasty (3.9% vs. 16.7%, P = 0.005). In cases with angiographic evidence of thrombus in the grafts, TEC maintained a significantly lower incidence of distal embolization than angioplasty (5.6% vs. 31.8%, P = 0.004). There were no statistical differences between the two groups regarding the incidence of other procedure-related complications, including death, myocardial infarction, or emergency coronary artery bypass grafting. TEC atherectomy appears to have a significantly lower incidence of distal embolization than balloon angioplasty when treating saphenous vein grafts, particularly in the presence of angiographically apparent thrombus.

Inappropriate use of bivariable analysis to screen risk factors for use in multivariable analysis.

The use of bivariable selection (BVS) for selecting variables to be used in multivariable analysis is inappropriate despite its common usage in medical sciences. In BVS, if the statistical p value of a risk factor in bivariable analysis is greater than an arbitrary value (often p = 0.05), then this factor will not be allowed to compete for inclusion in multivariable analysis. This type of variable selection is inappropriate because the BVS method wrongly rejects potentially important variables when the relationship between an outcome and a risk factor is confounded by any confounder and when this confounder is not properly controlled. This article uses both hypothetical and actual data to show how a nonsignificant risk factor in bivariable analysis may actually be a significant risk factor in multivariable analysis if confounding is properly controlled. Furthermore, problems resulting from the automated forward and stepwise modeling with or without the presence of confounding are also addressed. To avoid these improper procedures and deficiencies, alternatives in performing multivariable analysis, including advantages and disadvantages of the BVS method and automated stepwise modeling, are reviewed and discussed.

Comparison of percutaneous transluminal coronary angioplasty outcome and hospital costs for low-volume and high-volume operators.

Whether higher operator case volume is associated with improved percutaneous transluminal coronary angioplasty (PTCA) clinical and cost outcomes is the subject of this study. Hospital volume-related improvement in clinical outcomes has been shown for coronary artery bypass grafting (CABG) and PTCA. Physician case volume-related differences in clinical outcomes have not been clearly demonstrated, and differences in hospital costs have not been examined. For clinical and cost outcomes, risk-adjusted analysis of differences in PTCA outcomes has not been reported. In addition, controversy exists about the appropriate annual case volume considered adequate to maintain skills and achieve optimal clinical outcomes in performing PTCA procedures. We studied 2,350 PTCAs performed between March 1, 1991, and February 28, 1994. Physicians were divided into 2 volume groups: high (>50 cases/year) and low (<50 cases/year). The rate of emergency CABG after PTCA was 2.1% for high- and 3.9% for low-volume operators (p = 0.009). Hospital morbidity associated with PTCA was lower in high-than in low-volume operators (6.46% vs 10.73%, p <0.001). The risk-adjusted ratios for emergency CABG and morbidity were 2.05 (p = 0.005) and 1.79 (p <0.001), respectively. The length of stay averaged 4.07 +/- 4.54 days for high- and 4.49 +/- 4.33 days for low-volume operators (p = 0.003). Hospital costs averaged $7,977 +/-$7,269 for high- and $8,278 +/- $6,289 for low-volume operators (p = 0.065). The risk adjusted ratio was 1.091 (p = 0.004) for length of stay and 1.050 (p = 0.029) for cost. Thus, PTCA performed by high-volume operators is significantly less likely to require emergency CABG and is also significantly associated with lower hospital morbidity, shorter hospital length of stay, and lower hospital costs.

Subsets of ambulatory myocardial ischemia based on heart rate activity. Circadian distribution and response to anti-ischemic medication. The Angina and Silent Ischemia Study Group (ASIS)

BACKGROUND: Identification of whether episodes of ambulatory ischemia are caused by increases in myocardial oxygen demand or to episodic coronary vasoconstriction in patients with stable coronary disease may be important to guide selection of optimal anti-ischemic therapy and to gain insight into mechanisms responsible for adverse cardiac events. METHODS AND RESULTS: Mean minute heart rate activity during ambulatory ECG (AECG) monitoring was determined for 50 patients treated with propranolol, diltiazem, nifedipine, or placebo in a randomized, double-blind, crossover trial. Periods of heart rate increases of various magnitudes and durations and starting at various baseline heart rates on each therapy were identified throughout each 48-hour AECG recording, and the proportion of these periods associated with an ischemic episode was determined. The circadian variation of ischemic episodes categorized by the presence or absence of an increase in heart rate was analyzed. Eighty-one percent of ischemic episodes were preceded by an increase in heart rate > or = 5 beats per minute. The likelihood of developing ischemia associated with a heart rate increase was proportional to the magnitude and duration of the heart rate increase and the baseline heart rate before the increases in heart rate: likelihood ranged from 4% when the heart rate increased 5-9 beats per minute and lasted < 10 minutes to 60% when the heart rate increased > or = 20 beats per minute and lasted > or = 40 minutes. The likelihoods of developing ischemia based on changes in the heart rate variables were similar for each of the therapies. Propranolol therapy significantly reduced the magnitude and duration of heart rate increase and the baseline heart rate compared with therapy with placebo, diltiazem, or nifedipine (P < .001). Ischemic episodes associated with a heart rate increase displayed a daytime peak, whereas ischemia occurring without a heart rate increase occurred evenly throughout the day. Propranolol reduced the proportion of heart rate-related ischemic episodes and increased the proportion of non-heart rate-related episodes compared with placebo (P < .02), and nifedipine exerted the opposite effect (P = .005). Multivariate analysis indicated that the probability of developing ischemia was strongly associated with heart rate variables and was unaffected by time of day. CONCLUSIONS: Most episodes of ambulatory ischemia are associated with a preceding period of increased heart rate. The likelihood of developing ischemia is predicted by heart rate variables and unaffected by time of day. Anti-ischemic efficacy is generally a result of the medication's efficacy in reducing heart rate variables. A minority of ischemic episodes are not associated with preceding periods of increased heart rate, may be caused by episodic coronary vasoconstriction, and are more effectively reduced by nifedipine than propranolol.

Discordance between effects of anti-ischemic therapy on ambulatory ischemia, exercise performance and anginal symptoms in patients with stable angina pectoris. The Angina and Silent Ischemia Study Group (ASIS).

OBJECTIVES: We sought to define the extent to which the therapeutic efficacy of three single-drug regimens on ambulatory ischemia paralleled efficacy on other clinical manifestations of ischemia, specifically exercise test performance and anginal symptoms. BACKGROUND: Some studies have shown that the presence and severity of ambulatory ischemia are predictive of anginal symptoms and exercise test performance, whereas other studies have not. Less is known about effects of antianginal treatment and whether response to therapy for one clinical manifestation reflects therapeutic responses for other clinical manifestations. METHODS: We studied 50 patients in the Angina and Silent Ischemia Study who had documented coronary disease, an exercise test positive for ischemia, the presence of ambulatory and asymptomatic ischemia on ambulatory electrocardiographic (ECG) Holter monitoring and stable anginal symptoms. Patients received maximally tolerated doses of sustained release propranolol (mean 293 mg/day), sustained release diltiazem (mean 350 mg/day), nifedipine (mean 79 mg/day) and placebo, each for 2-week periods in a double-blind, crossover fashion. Patients' responses to treatment were assessed by 48-h ambulatory ECG monitoring, exercise test (standard Bruce protocol) and diaries of angina. Levels of efficacy for each agent and for each clinical measure were compared using Spearman correlation analysis. RESULTS: With placebo there was no correlation among the frequency of ischemic episodes by ambulatory ECG monitoring, exercise time to 1.0-mm ST segment depression or frequency of anginal episodes. Furthermore, for a given patient the efficacy of each active medication in reducing ambulatory ischemia was not correlated with response in anginal symptoms or exercise test performance (r = -0.21 to 0.24, p = NS). Within each of these clinical measures, efficacy of one drug was more strongly correlated with efficacy of another drug (r = 0.64 to 0.81 for ambulatory ischemia, 0.48 to 0.56 for exercise test performance and 0.16 to 0.54 for anginal symptoms). CONCLUSIONS: Different measures of ischemia, specifically ambulatory ischemia assessed by ambulatory ECG monitoring, exercise performance on exercise test and anginal symptoms, are independent. Efficacy for each clinical end point must be assessed separately when considering response to drug treatment.

Comparison of propranolol, diltiazem, and nifedipine in the treatment of ambulatory ischemia in patients with stable angina. Differential effects on ambulatory ischemia, exercise performance, and anginal symptoms. The ASIS Study Group.

Episodes of transient myocardial ischemia during ambulatory activities are common in patients with stable coronary artery disease and who are often asymptomatic. Selection of therapy for episodes of asymptomatic ischemia is limited by a lack of direct comparative studies. To determine the most effective monotherapy for patients with stable angina and a high frequency of asymptomatic ischemic episodes, propranolol-LA (mean daily dose, 293 mg), diltiazem-SR (mean daily dose, 350 mg), nifedipine (mean daily dose, 79 mg) were each compared with placebo, each for 2 weeks, in a randomized, double-blinded, crossover trial. Entry criteria were a positive exercise treadmill test during placebo therapy characterized by 1.0 mm or more ST segment depression and angina pectoris, and six or more episodes of transient ST segment depression of 1.0 mm or more on a 48-hour ambulatory electrocardiogram. One hundred ninety-four patients were screened, 63 were eligible and received randomized therapy, of which 56 patients completed at least two of the four treatment periods and were included in an intent-to-treat analysis. Fifty patients completed all four treatment phases and were included in the protocol-completed analysis. Anti-ischemia efficacy was assessed by 48-hour ambulatory electrocardiographic monitoring, exercise treadmill tests, and anginal diaries. Ninety-four percent of all episodes of ambulatory ischemia were asymptomatic. Compared with placebo, only propranolol was associated with a marked reduction in all manifestations of asymptomatic ischemia during ambulatory electrocardiographic monitoring (2.3 versus 1.0 episodes/24 hr; mean duration of ischemia per 24 hours, 43.6 versus 5.7 minutes; both p less than 0.0001). Diltiazem's reduction of the frequency of episodes compared with placebo (2.3 versus 1.9 episodes/24 hr) was associated with a trend (p = 0.08) in the protocol-completed analysis and with a significant reduction in the intent-to-treat analysis (p = 0.03). Nifedipine had no significant effect on any measured variable of ambulatory ischemia. The dosages of medication used may have been excessive for some patients, and a more beneficial effect may have been evident at a lower dose. In contrast to the marked effects of the active agents on ambulatory asymptomatic ischemia, the effects on exercise performance and angina pectoris were slight. The active agents modestly improved treadmill exercise duration time until 1 mm ST segment depression (3%), and only propranolol and diltiazem had significant effects. Only diltiazem significantly prolonged the total exercise time. Anginal frequency was significantly decreased by both propranolol and diltiazem.(ABSTRACT TRUNCATED AT 400 WORDS)

Suppression of silent ischemia by metoprolol without alteration of morning increase of platelet aggregability in patients with stable coronary artery disease.

To determine the effect of metoprolol on silent ischemia and platelet aggregability, 10 patients with coronary artery disease were studied with a randomized, double-blind, placebo-controlled, crossover trial. Patients were treated with metoprolol (200 mg b.i.d.) or placebo for 1 week and then received the alternate therapy. Two days before the end of each treatment period, platelet aggregability was studied for 24 hours, and a 48-hour ambulatory electrocardiogram was obtained. Compared with placebo, metoprolol significantly decreased the total number (from 26 to 4, p less than 0.1) and duration (from 735 to 84 minutes, p less than 0.01) of silent ischemic episodes. This decrease was accompanied by a decrease in the mean blood pressure (from 127/81 to 118/71 mm Hg, p less than 0.01) and the mean heart rate (from 70 to 54 beats/min, p less than 0.01). The incidence of silent ischemic episodes in the morning was significantly higher in untreated patients than in treated patients. The few episodes observed during metoprolol treatment occurred at the same time as the peak incidence observed during placebo treatment. During placebo treatment, platelet aggregability increased from 6:00 to 9:00 AM as reflected by a decrease in the threshold concentrations of ADP and epinephrine required to induce biphasic platelet aggregation (from 4.8 +/- 0.8 to 2.6 +/- 0.4 microM, p less than 0.02; and from 7.3 +/- 2.3 to 1.8 +/- 0.9 microM, respectively, p less than 0.02). Metoprolol did not alter the basal level nor blunt the morning increase of platelet aggregability.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of a conductance catheter to detect increased left ventricular inotropic state by end-systolic pressure-volume analysis.

The slope of the left ventricular end-systolic pressure-volume relationship is thought to be a load-independent index of contractile state. However, clinical application requires a practical technique to simultaneously measure pressure and volume in man. We used a left ventricular conductance catheter to derive the left ventricular end-systolic pressure-volume relationship over a range of arterial pressures during nitroprusside infusion and washout in 14 patients, and to characterize the effect of dobutamine, a positive inotropic drug. End-systole was defined as the maximum pressure-to-volume ratio. Dobutamine (5 micrograms/kg/min) increased the slope of the end-systolic pressure-volume relationship in 11 of 14 patients, the mean slope increasing by 43% from 1.4 +/- 0.1 to 2.1 +/- 0.2 mm Hg/% end-diastolic volume (p less than 0.01). In 12 of 14 patients there was a leftward and upward shift of the end-systolic pressure-volume relationship with dobutamine. T quantitate this shift, we derived left ventricular pressure at control end-systolic volume before and after dobutamine. Dobutamine increased the mean end-systolic pressure at control end-systolic volume in 12 of 14 patients, the average increased by 37% from 134 +/- 10 to 189 +/- 23 mm Hg (p less than 0.01). We conclude that the conductance catheter can be used in man to detect a drug-induced change in left ventricular contractile state. This technique may be useful in the evaluation of drugs with positive inotropic actions, and in assessing the response of individual patients to positive inotropic agents.

Silent myocardial ischemia in asymptomatic survivors of unrecognized myocardial infarction and matched controls.

Although silent myocardial ischemia (SI) occurs frequently in patients with angina and is of prognostic significance, little is known of its occurrence in other subgroups. We assessed the incidence of SI in offspring of Framingham Heart Study (FHS) patients following unrecognized myocardial infarction (UMI) and in controls without MI but who were matched for age, sex, hypertension, diabetes, smoking, and total cholesterol at entry into the FHS. Of the 20 UMI patients, six had died and one with left bundle branch block was excluded. The remaining 13 UMI patients and 26 control patients underwent 24-hour ambulatory electrocardiographic monitoring (AECG) for SI. Two patients (one from each group) with angina were excluded from the AECG analysis. Only two (15.4%) of the UMI patients and two (7.7%) of the control patients had any AECG evidence of SI. These preliminary results suggest that routine monitoring for SI is not indicated in asymptomatic long-term survivors of UMI or in asymptomatic patients without prior MI but with otherwise similar risk profiles.

Detection of pacing-induced myocardial ischemia by endocardial electrograms recorded during cardiac catheterization.

Rapid atrial pacing confirms myocardial ischemia in patients with coronary artery disease when angina is provoked, and is accompanied by an increase in left ventricular end-diastolic pressure. In such cases, abnormalities in the surface electrocardiogram (ECG) are often not apparent. To enhance detection of subendocardial ischemia during rapid atrial pacing, local unipolar electrograms were recorded from the tip of a 0.025 in. (0.064 cm) diameter guidewire positioned against the endocardial surface of potentially ischemic regions. Endocardial electrograms, left ventricular end-diastolic pressure and multiple surface ECG leads were recorded during rapid atrial pacing in 21 patients with coronary artery disease. Before pacing, endocardial electrograms in all 21 patients were free of ST elevation. Marked ST elevation was apparent in 17 of the 21 patients after rapid atrial pacing and could be abolished by nitroglycerin. Moreover, in several patients, endocardial ST elevation after rapid atrial pacing was abolished after successful percutaneous transluminal coronary angioplasty of the critically stenosed artery supplying the ischemic region of myocardium. It is concluded that ST elevation in the endocardial electrogram after rapid atrial pacing is a reflection of myocardial ischemia and may be a sensitive marker of pacing-induced ischemia appearing earlier than angina, postpacing increase in left ventricular end-diastolic pressure or ST depression in the surface ECG.

Comparison of amplitude-modulated (direct) and frequency-modulated ambulatory techniques for recording ischemic electrocardiographic changes.

Continuous ambulatory electrocardiographic monitoring of ST-segment configuration has become a useful technique for evaluation of myocardial ischemia. Concern that direct or amplitude-modulated (AM) recording and playback systems have inherent limitations that cause inaccurate ST-segment recordings has led to preference for frequency-modulated (FM) devices. To determine the accuracy of AM and FM ambulatory electrocardiographic systems, the signal was compared from the same set of 2 bipolar leads simultaneously recorded by standard electrocardiography and AM and FM recorders in 14 patients during treadmill exercise. Also, simultaneous AM and FM recorders were compared in 9 ambulatory patients in 16 monitoring sessions. The AM recording system accurately reproduced ST segments recorded during treadmill exercise (range 4.0 mm of ST-segment depression to 2.0 mm of ST elevation) when measured at the J point (r = 0.91, p less than 0.0001), and 0.08 second after the J point (r = 0.95, p less than 0.0001). FM recording was equally accurate (r = 0.89 and 0.95, respectively, p less than 0.0001). Similarly, during ambulatory recording, the AM technique accurately recorded maximal ST depression in each episode as recorded by the FM device (28 episodes, range 0 to 3 mm of ST depression, r = 0.85, p less than 0.0001). Both AM and FM ambulatory electrocardiographic systems can accurately reproduce ST-segment deviation associated with ischemia and can be used to monitor transient ST-segment changes in patients with coronary artery disease.

Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries.

Acetylcholine is believed to dilate normal blood vessels by promoting the release of a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). By contrast, if the endothelium is removed experimentally, acetylcholine constricts blood vessels. We tested the hypothesis that muscarinic cholinergic vasodilation is impaired in coronary atherosclerosis. Graded concentrations of acetylcholine and, for comparison, the nonendothelial-dependent vasodilator nitroglycerin were infused into the left anterior descending artery of eight patients with advanced coronary stenoses (greater than 50 percent narrowing), four subjects with angiographically normal coronary arteries, and six patients with mild coronary atherosclerosis (less than 20 percent narrowing). Vascular responses were evaluated by quantitative angiography. In several segments each of four normal coronary arteries, acetylcholine caused a dose-dependent dilation from a control diameter of 1.94 +/- 0.16 mm to 2.16 +/- 0.15 mm with the maximal acetylcholine dose (P less than 0.01). In contrast, all eight of the arteries with advanced stenoses showed dose-dependent constriction, from 1.05 +/- 0.05 to 0.32 +/- 0.16 mm at the highest concentration of acetylcholine (P less than 0.01), with temporary occlusion in five. Five of six vessels with minimal disease also constricted in response to acetylcholine. All vessels dilated in response to nitroglycerin, however. We conclude that paradoxical vasoconstriction induced by acetylcholine occurs early as well as late in the course of coronary atherosclerosis. Our preliminary findings suggest that the abnormal vascular response to acetylcholine may represent a defect in endothelial vasodilator function, and may be important in the pathogenesis of coronary vasospasm.

Value of the intracoronary electrocardiogram to monitor myocardial ischemia during percutaneous transluminal coronary angioplasty.

To enhance detection of ischemia during percutaneous transluminal coronary angioplasty (PTCA), unipolar intracoronary electrocardiograms (ECGs) were recorded during PTCA in 25 patients from the tips of guidewires positioned distal to stenoses being dilated. Surface electrocardiographic leads chosen to reflect likely areas of reversible ischemia during PTCA were recorded simultaneously. In 21 of 29 stenoses dilated (72%), ST segment elevation and/or T wave peaking in intracoronary ECG appeared during balloon inflation and disappeared after deflation, accompanied by transient angina on 19 occasions. Two patients had transient ST segment elevation in intracoronary ECGs during PTCA without associated angina. ST changes in the surface ECG during PTCA were seen on only nine occasions (31%), always accompanied by ST segment elevation in the intracoronary ECG that appeared earlier and was of much greater magnitude. Five patients with prior myocardial infarction and aneurysm formation had fixed ST segment elevation in the intracoronary ECG unrelated to balloon inflation. Myocardial ischemia during PTCA can be detected easily with intracoronary ECGs and with greater sensitivity than that of the surface ECG. Furthermore, intracoronary ECGs may help to clarify the nature of chest pain during balloon inflation or during suspected complications.