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Relation between QT dispersion and the extent of myocardial ischemia in patients with three-vessel coronary artery disease.

The aim of the study was to examine the relation between the extent of myocardial ischemia and changes in QT interval dispersion in patients with obstructive coronary artery disease and in patients with normal coronary arteries. QT interval dispersion reflects regional variations in ventricular repolarization and cardiac electrical instability. Previous studies showed QT interval dispersion changes during episodes of myocardial ischemia in patients with coronary artery disease, but no data on the relation between extent of myocardial ischemia and degree of QT interval dispersion changes are available. To assess the effects of myocardial ischemia on myocardial repolarization by analyzing the change in QT dispersion during incremental atrial pacing, we studied 33 patients (7 women and 26 men, mean age 60.1 +/- 5.1 years, 18 patients with normal coronary arteries, 15 patients with coronary 3-vessel disease). QT dispersion was measured at baseline, after each pacing period, within 30 seconds after cessation of pacing ("peak ischemic stress"), and at 1-minute intervals for up to 5 minutes. Paired blood samples for determination of serum lactate were withdrawn from the coronary sinus and radial artery to determine the cardiac lactate extraction ratio at each point of electrocardiographic registration. In patients with coronary artery disease, QT dispersion increased from a baseline value of 39 +/- 7 ms to a peak ischemic stress value of 63 +/- 10 ms (p <0.0001). Patients with normal coronary arteries showed almost unchanged values of QT dispersion (41 +/- 9 vs 42 +/- 7 ms). There was a significant relation between the pacing-induced change in QT dispersion and the induced change in myocardial lactate extraction ratio (r = 0.76, p <0.0001). The change in QT dispersion (baseline vs peak pacing stress) was related to the extent of the cardiac lactate extraction ratio (r = -0.79, p <0.0001). These data indicate that the severity or extent of induced myocardial ischemia was related to the degree of induced changes of the variability in the timing of the ventricular recovery pattern.

Aged↗

[Effect of drugs on the tonus of the coronary vessels in hormonal imbalance].

The excessive administration of estrogens leads to the growth of sensitivity of coronary vessel smooth muscles cholinoreceptors to cholinomimetics. Excessive administration of progesterone stimulates the sensitivity of adrenoreceptors of coronary vessel smooth muscles to adrenomimetics.

4-Aminobenzoic Acid↗

Angiotensin II and structural remodeling of coronary vessels in rats.

A perivascular fibrosis of intramyocardial coronary arterioles, composed of type I fibrillar collagen, is associated with chronic elevations in circulating angiotensin II (AngII). The hypothesis tested herein is that coronary vascular remodelling involving cardiac interstitial fibroblasts is responsible for this fibrous tissue response. This morphologic study therefore had several objectives: (1) to determine whether a continuous infusion of AngII (150 ng/min/kg) would alter plasma fibronectin (pFN) labeling of coronary vessels, and to identify the level of the coronary vasculature involved in this response; (2) to determine whether the chronic administration of AngII would ultimately lead to enhanced type I collagen synthesis and a perivascular fibrosis of arterioles, and to identify the cellular response associated with this fibrogenesis. Accordingly, the hearts of rats receiving AngII over the course of 2 weeks were examined at 1, 2, 4, 7, 10, and 14 days. From the same heart, serial sections were obtained for pFN immunofluorescent microscopy, PCNA immunolabeling, in situ hybridization with a type I collagen probe, and light microscopy to address cellular response (hematoxylin and eosin) and formation of fibrillar collagen (picrosirius red). We found (1) increased coronary arteriolar staining with pFN antibody on day 2, with an increasing number of vessels involved over 14 days; (2) pFN appearing first in the media and adventitia and subsequently the interstitial space; (3) fibroblast proliferation on days 2 and 4, and enhanced expression of type I collagen mRNA in these adventitial and interstitial cells on days 4 and 7; (4) accumulation of macrophages in the adventitia of involved vessels during the period of observation; and (5) a perivascular fibrosis of involved vessels on day 14.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Evaluating the potential cost-effectiveness of stenting as a treatment for symptomatic single-vessel coronary disease. Use of a decision-analytic model.

BACKGROUND: Coronary stenting appears to provide more predictable immediate results and lower rates of restenosis than conventional balloon angioplasty for selected lesion types, but its hospital costs are significantly higher. This study was designed to evaluate the potential cost-effectiveness of Palmaz-Schatz coronary stenting relative to conventional balloon angioplasty for the treatment of patients with symptomatic, single-vessel coronary disease. METHODS AND RESULTS: We developed a decision-analytic model to predict quality-adjusted life expectancy and lifetime treatment costs for patients with symptomatic, single-vessel coronary disease treated by either Palmaz-Schatz stenting (PSS) or conventional angioplasty (PTCA). Estimates of the probabilities of overall procedural success (PTCA, 97%; PSS, 98%), abrupt closure requiring emergency bypass surgery (PTCA, 1.0%; PSS, 0.6%), and angiographic restenosis (PTCA, 37%; PSS, 20%) were derived from review of the literature published as of September 1993. Procedural costs were based on the true economic (ie, variable) costs of each procedure at Boston's Beth Israel Hospital. On the basis of these data, coronary stenting was estimated to result in a higher quality-adjusted life expectancy than conventional angioplasty but to incur additional costs as well. Compared with conventional angioplasty, stenting had an estimated incremental cost-effectiveness ratio of $23,600 per quality-adjusted life year gained. Although the cost-effectiveness ratio for stenting changed with variations in assumptions about the relative costs and restenosis rates, it remained less than $40,000 per quality-adjusted year of life gained--and thus was similar to many other accepted medical treatments--unless the stent angiographic restenosis rate was > 23%, the angioplasty restenosis rate was < 34%, or the cost of stenting (including vascular complications) exceeded that of conventional angioplasty by more than $3000. The alternative strategy of secondary stenting (initial angioplasty followed by stenting only for symptomatic restenosis) was estimated to be both less effective and less cost-effective than primary stenting over a wide range of plausible assumptions and thus does not appear to be cost-effective when primary stenting is also an option. CONCLUSIONS: Decision-analytic modeling can be used to evaluate the potential cost-effectiveness of new coronary interventions. Our analysis suggests that despite its higher cost, elective coronary stenting may be a reasonably cost-effective treatment for selected patients with single-vessel coronary disease. Primary stenting is unlikely to be cost-effective for lesions with a low probability of restenosis (eg, < 30%) or for patients for whom the cost of stenting is expected to be much higher than usual (eg, because of a high risk of vascular complications). Given the sensitivity of the cost-effectiveness ratios to even modest variations in the relative restenosis rates and cost estimates, future studies will be necessary to determine more precisely the cost-effectiveness of coronary stenting for specific patient and lesion subsets.

Angioplasty, Balloon, Coronary↗

[Effects of coronary angioplasty on heart rate variability explored in the domain of time and frequency in patients with one-vessel coronary disease].

BACKGROUND: Heart period variability is frequently reduced in patients with coronary artery disease. Although the mechanism for this reduction is still unclear, it seems to reflect alterations in cardiac autonomic control. In this study we have evaluated the relation between reversible segmental left ventricular dysfunction and time and frequency domain measures of heart period variability in patients with coronary artery disease. METHODS AND RESULTS: Echocardiographic segmental left ventricular wall motion and time and frequency domain measures of heart period variability were evaluated in 32 patients with one-vessel coronary artery disease before and 16-24 days after successful percutaneous transluminal coronary angioplasty (PTCA). At baseline examination 12 patients (Group A) had normal and 20 (Group B) abnormal regional wall motion. Prevalence of previous myocardial infarction was higher and mean angiographic ejection fraction lower in Group B than in Group A. At baseline, time domain measures were comparable between the 2 groups, while low frequency (LF) and high frequency (HF) power were lower in Group B than in Group A. After PTCA, in Group A regional wall motion and time and frequency domain measures of heart period variability were unchanged. In Group B summed segment score improved from 17.1 +/- 3.6 to 12.8 +/- 2.0 (p < 0.01) and a significant increase occurred in standard deviation of the average normal RR (NN) intervals for all 5-minute segments of a 24-hour recording (SDNN index), in root mean square successive difference (r-MSSD) and in the percentage of differences between adjacent NN intervals > 50 msec (pNN50). In this group also LF and HF power (logarithmic units) increased from 6.14 +/- 0.23 to 6.35 +/- 0.34 (p < 0.01) and from 5.43 +/- 0.32 to 5.68 +/- 0.52 (p < 0.01) respectively. There was no correlation between measures of heart period variability, summed segment score, and left ventricular ejection fraction. CONCLUSIONS: This study demonstrates that segmental left ventricular dysfunction is involved in determining sympathovagal imbalance in patients with one-vessel coronary artery disease; the reversal of left ventricular dysfunction by successful PTCA improves heart period variability. These findings support the hypothesis that alterations in cardiac geometry may influence the discharge of afferent sympathetic mechanoreceptors, thus contributing to the derangement in autonomic control of heart rate.

Aged↗

Design of the 'Stent or Surgery' trial (SoS): a randomized controlled trial to compare coronary artery bypass grafting with percutaneous transluminal coronary angioplasty and primary stent implantation in patients with multi-vessel coronary artery disease.

The 'Stent or Surgery' trial (SoS) is a randomized controlled trial to compare coronary artery bypass grafting with percutaneous transluminal coronary angioplasty and primary stent implantation in patients with multi-vessel coronary artery disease. This is a multicentre, multinational venture involving over 40 centres in 12 countries throughout Europe and Canada. Eligible and consenting patients will be randomly allocated, in equal proportions, to open revascularization by CABG or by PTCA with the primary implantation of intracoronary stents. The trial design is pragmatic and imposes few protocol restrictions in patient selection, surgical and intervention techniques or adjunctive medication schedules. The rationale and design of the trial are discussed, including important sub-studies, examining quality of life, neuropsychological outcome, cost and cost benefit.

Angioplasty, Balloon, Coronary↗

Efficacy of calcium channel blocker therapy for angina pectoris resulting from small-vessel coronary artery disease and abnormal vasodilator reserve.

Abnormal vasodilator reserve of the coronary microcirculation is a frequent mechanism of angina pectoris in patients with angiographically normal coronary arteries. To assess the effect of calcium channel blocking agents on symptoms and exercise capacity, 26 patients shown to have angina pectoris because of abnormally small coronary arteries and limited vasodilator reserve underwent randomized, double-blind, placebo-controlled outpatient study, with 1 month for each period. An unblinded lead-in phase determined the best dose of verapamil (17 patients) or nifedipine (9 patients). Exercise testing using bicycle ergometry was performed at the end of each period. Four patients interrupted the placebo period and 1 patient interrupted both placebo and drug period because of frequent and severe chest pain. While receiving calcium channel blocker drugs, patients who completed both phases of the study recorded fewer episodes of angina (21 +/- 21 vs 35 +/- 27, p less than 0.001) and consumed fewer nitroglycerin tablets (23 +/- 27 vs 41 +/- 50, p less than 0.001) than during the placebo period. Exercise duration was slightly but significantly prolonged (278 +/- 129 vs 231 +/- 136 seconds, p less than 0.025) during drug treatment compared with placebo, and significantly fewer patients terminated exercise with chest pain while receiving drug treatment. Subjectively, 22 of 26 patients felt better on the calcium channel blocker than on placebo. Thus, calcium channel blocker therapy appears to be beneficial in controlling angina and improving exercise tolerance in patients with angina pectoris resulting from abnormally small coronary arteries and limited vasodilator reserve.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Myocardial protection by intravenous diltiazem during angioplasty of single-vessel coronary artery disease.

The possible cardioprotective effect of diltiazem during ischemia caused by percutaneous transluminal coronary angioplasty was tested. Electrocardiograms and myocardial lactate, hypoxanthine and urate production were determined in 26 patients with a stenosis in the left anterior descending artery without angiographically demonstrable collaterals. Measurements took place before angioplasty, after each of 4 occlusions and 15 minutes after the last balloon inflation. Patients were randomly given placebo or DL-diltiazem (0.4 mg/kg as a bolus intravenously, followed by an infusion of 15 mg/hr). During angioplasty the ST-segment elevation for the anterior wall leads V2, V4 and V6, and the intracoronary lead was similar for both groups, as was lactate release. Diltiazem significantly reduced cardiac hypoxanthine release immediately after angioplasty from 63 to 88% (p less than 0.05). The drug diminished urate production after the last dilatation by 82% (p less than 0.05). In conclusion, intravenous infusion of diltiazem reduced cardiac adenosine triphosphate breakdown during angioplasty as shown by diminished hypoxanthine and urate production. In contrast, diltiazem was unable to attenuate ST-segment elevation and lactate release.

Adenosine Triphosphate↗

Noninvasive identification of left main and triple vessel coronary artery disease: improved accuracy using quantitative analysis of regional myocardial stress distribution and washout of thallium-201.

The capabilities of visual and quantitative analysis of stress redistribution thallium-201 scintigrams, exercise electrocardiography and exercise blood pressure response were compared for correct identification of extensive coronary disease, defined as left main or triple vessel coronary artery disease, or both (50% or more luminal diameter coronary narrowing), in 105 consecutive patients with suspected coronary artery disease. Extensive disease was present in 56 patients and the remaining 49 had either less extensive coronary artery disease (n = 34) or normal coronary arteriograms (n = 15). Although exercise blood pressure response, exercise electrocardiography and visual thallium-201 analysis were highly specific (98, 88 and 96%, respectively), they were insensitive for identification of patients with extensive disease (14, 45 and 16%, respectively). Quantitative thallium-201 analysis significantly improved the sensitivity of visual thallium-201 analysis for identification of patients with extensive disease (from 16 to 63%, p less than 0.001) without a significant loss of specificity (96 versus 86%, p = NS). Eighteen (64%) of the 28 patients who were misclassified by visual analysis as having less extensive disease were correctly classified as having extensive disease by virtue of quantitative analysis of regional myocardial thallium-201 washout. When the results of quantitative thallium-201 analysis were combined with those of blood pressure and electrocardiographic response to exercise, the sensitivity and specificity for identification of patients with extensive disease was 86 and 76%, respectively, and the highest overall accuracy (0.82) was obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparative effects of nitroglycerin, nifedipine and metoprolol on regional left ventricular function in patients with one-vessel coronary disease.

To compare acute effects of nitroglycerin (0.8 mg sublingually), nifedipine (5 ng/kg/min i.v.) and metoprolol (0.15 mg/kg i.v.) on normal, ischemic and scarred myocardial segments in man, we performed simultaneous hemodynamic and radionuclide measurements of left ventricular functions. Sixteen patients with isolated left anterior descending (LAD) disease were studied at rest and during exercise. Nine patients had angina and exercise-induced ischemia (LAD stenosis) and seven patients had previous transmural myocardial infarction and no ischemic changes during thallium imaging (LAD occlusion). The effects of the drugs on regional ejection fraction of the involved anteroseptal region and the normal posterolateral area were compared. Global ejection fraction at rest did not change after nitroglycerin, increased after nifedipine and decreased after metoprolol. In patients with ischemia, the exercise ejection fraction improved after all drugs due to increased regional ejection fraction in ischemic segments: i.e., a regional antiischemic effect evidenced by improved regional function could be demonstrated with all three agents. Regional ejection fraction increased from 35.8 +/- 19.5% to 66.2 +/- 15.2% (+/- SD) after nitroglycerin (p less than 0.001), to 61.7 +/- 8.7% after nifedipine (p less than 0.001), and to 48.4 +/- 7.0% after metoprolol (p less than 0.01). In regions of myocardial scar, regional ejection fraction was not changed after any drug. In normal areas, regional ejection fraction remained unchanged after nitroglycerin and nifedipine, but decreased after metoprolol. Despite similar antiischemic effects of all three drugs, underlying hemodynamic mechanisms were quite different and may provide a rationale for combined forms of treatment. These results may help to select optimal drug combinations to improve myocardial performance in patients with chronic ischemic heart disease.

Adult↗