Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease

BACKGROUND. The treadmill exercise test identifies patients with different degrees of risk of death from cardiovascular events. We devised a prognostic score, based on the results of treadmill exercise testing, that accurately predicts outcome among inpatients referred for cardiac catheterization. This study was designed to determine whether this score could also accurately predict prognosis in unselected outpatients. METHODS. We prospectively studied 613 consecutive outpatients with suspected coronary disease who were referred for exercise testing between 1983 and 1985. Follow-up was 98 percent complete at four years. The treadmill score was calculated as follows: duration of exercise in minutes--(5 x the maximal ST-segment deviation during or after exercise, in millimeters)--(4 x the treadmill angina index). The numerical treadmill angina index was 0 for no angina, 1 for nonlimiting angina, and 2 for exercise-limiting angina. Treadmill scores ranged from -25 (indicating the highest risk) to +15 (indicating the lowest risk). RESULTS. Predicted outcomes for the outpatients, based on their treadmill scores, agreed closely with the observed outcomes. The score accurately separated patients who subsequently died from those who lived for four years (area under the receiver-operating-characteristic curve = 0.849). The treadmill score was a better discriminator than the clinical data and was even more useful for outpatients than it had been for inpatients. Approximately two thirds of the outpatients had treadmill scores indicating low risk (greater than or equal to +5), reflecting longer exercise times and little or no ST-segment deviation, and their four-year survival rate was 99 percent (average annual mortality rate, 0.25 percent). Four percent of the outpatients had scores indicating high risk (less than -10), reflecting shorter exercise times and more severe ST-segment deviation; their four-year survival rate was 79 percent (average annual mortality rate, 5 percent). CONCLUSIONS. The treadmill score is a useful and valid tool that can help clinicians determine prognosis and decide whether to refer outpatients with suspected coronary disease for cardiac catheterization. In this study, it was a better predictor of outcome than the clinical assessment.     

Effect of exercise on coronary endothelial function in patients with coronary artery disease

BACKGROUND: Studies of the cardioprotective effects of exercise training in patients with coronary artery disease have yielded contradictory results. Exercise training has been associated with improvement in myocardial perfusion even in patients who have progression of coronary atherosclerosis. We therefore conducted a prospective study of the effect of exercise training on endothelial function in patients with coronary artery disease. METHODS: We randomly assigned 19 patients with coronary endothelial dysfunction, indicated by abnormal acetylcholine-induced vasoconstriction, to an exercise-training group (10 patients) or a control group (9 patients). To reduce confounding, patients with coronary risk factors that could be influenced by exercise training (such as diabetes, hypertension, hypercholesterolemia, and smoking) were excluded. In an initial study and after four weeks, the changes in vascular diameter in response to the intracoronary infusion of increasing doses of acetylcholine (0.072, 0.72, and 7.2 microg per minute) were assessed. The mean peak flow velocity was measured by Doppler velocimetry, and the diameter of epicardial coronary vessels was measured by quantitative coronary angiography. RESULTS: In the initial study, the two groups had similar vasoconstrictive responses to acetylcholine. After four weeks of exercise training, coronary-artery constriction in response to acetylcholine at a dose of 7.2 microg per minute was reduced by 54 percent (from a mean [+/-SE] decrease in the luminal diameter of 0.41+/-0.05 mm in the initial study to a decrease of 0.19+/-0.07 mm at four weeks; P<0.05 for the comparison with the change in the control group). In the exercise-training group, the increases in mean peak flow velocity in response to 0.072, 0.72, and 7.2 microg of acetylcholine per minute were 12+/-7, 36+/-11, and 78+/-16 percent, respectively, in the initial study. After four weeks of exercise, the increases in response to acetylcholine were 27+/-7, 73+/-19, and 142+/-28 percent (P<0.01 for the comparison with the control group). Coronary blood-flow reserve (the ratio of the mean peak flow velocity after adenosine infusion to the resting velocity) increased by 29 percent after four weeks of exercise (from 2.8+/-0.2 in the initial study to 3.6+/-0.2 after four weeks; P<0.01 for the comparison with the control group). CONCLUSIONS: Exercise training improves endothelium-dependent vasodilatation both in epicardial coronary vessels and in resistance vessels in patients with coronary artery disease.     

Comparison of coronary artery bypass grafting with percutaneous coronary intervention for unprotected left main coronary artery disease

Purpose

Coronary artery bypass grafting (CABG) is the optimal treatment option for left main coronary artery disease (LMCAD). However, LMCAD remains a constant topic of discussion between cardiac surgeons and interventional cardiologists. The aim of this study was to assess the efficacy of LMCAD treatments by comparing the mid-term outcomes of CABG and percutaneous coronary intervention (PCI) using bare metal stents or drug-eluting stents (DESs).

Materials and Methods

The study population was comprised of 199 consecutive patients admitted with unprotected LMCAD. All of the patients were assigned to PCI (88 patients) or CABG (111 patients). The primary clinical end point indicated death, stroke of acute coronary syndrome (ACS).

Results

Patients assigned to PCI were at higher operative risk than patients scheduled for CABG (6.49±4.09 vs. 4.81±2.67, p=0.0032). Comparison of the group that received DESs with the CABG group did not reveal any differences in major adverse cardio-cerebral events (MACCE) occurrence (21% vs. 16%, p=NS). Patients in the CABG and PCI groups died with similar frequency (11% vs. 16%, p=NS). The mortality rate in the CABG group was higher than among those treated with DES (11% vs. 3%, p=0.049). The rate of ACS was higher in the PCI group than in the CABG group (13% vs. 4%, p=0.016).

Conclusion

Despite the fact that patients treated with PCI were at higher operative risk, PCI with DES was shown to be comparable to CABG in terms of mortality, stroke and ACS. However, the frequency of repeat revascularizations remains a constant concern with PCI.     

Hemodynamic effects of sildenafil in men with severe coronary artery disease

BACKGROUND: The cardiovascular effects of sildenafil are important because of the frequent presence of underlying cardiac disease in men with erectile dysfunction and reports indicating serious cardiac events temporally associated with the use of this drug. METHODS: We assessed the systemic, pulmonary, and coronary hemodynamic effects of oral sildenafil (100 mg) in 14 men (mean [+/-SD] age, 61+/-11 years) with severe stenosis of at least one coronary artery (stenosis of >70 percent of the vessel diameter) who were scheduled to undergo percutaneous coronary revascularization. Blood-flow velocity and flow reserve were assessed with a Doppler guidewire in 25 coronary arteries, including 13 severely diseased arteries (mean stenosis, 78+/-7 percent) and 12 arteries without stenosis, used as a reference; maximal hyperemia was induced (to assess flow reserve) with the intracoronary administration of adenosine both before and after sildenafil. RESULTS: Oral sildenafil produced only small decreases (<10 percent) in systemic arterial and pulmonary arterial pressures, and it had no effect on pulmonary-capillary wedge pressure, right atrial pressure, heart rate, or cardiac output. There were no significant changes in average peak coronary flow velocity, coronary-artery diameter, volumetric coronary blood flow, or coronary vascular resistance. Coronary flow reserve at base line was lower in the stenosed arteries (1.26+/-0.26) than in the reference arteries (2.19+/-0.44) and increased about 13 percent in both groups of arteries combined after the administration of sildenafil (from 1.70+/-0.59 to 1.92+/-0.72, P=0.003). The ratio of coronary flow reserve in coronary arteries with stenosis to that in the reference arteries (0.57+/-0.14) was not affected by sildenafil. CONCLUSIONS: No adverse cardiovascular effects of oral sildenafil were detected in men with severe coronary artery disease.     

Aerobic exercise performance correlates with post-ischemic flow-mediated dilation of the brachial artery in young healthy men

In older healthy men, aerobic exercise capacity is related to postischemic flow-mediated dilation of the brachial artery (FMD), but corresponding data in a younger population is not available. In addition, whether submaximal aerobic exercise performance also correlates with this kind of vasomotor reactivity is not known. Therefore, in 15 nonsmoking young healthy men [age 27 (5) years; body mass index: 24 (2) kg/m²; mean (SD)] with different levels of ordinary physical activity, but not performing upper-extremity training, we measured FMD at 1 min after reactive hyperemia, and pulmonary oxygen uptake (O₂) at ventilatory anaerobic threshold (O₂AT) and at peak effort (peak O₂) during an incremental exercise on a treadmill. In our participants, FMD was 9.1 (3.4)%, O₂AT was 40.72 (5.92) ml/kg per min, and peak O₂ was 52.95 (8.13) ml/kg per min. Using bivariate Pearsons correlation, and in separate multivariate regression analyses, O₂AT and peak VO₂ showed a significant and reasonably good correlation with FMD (r=0.84, P<0.001 and r=0.77, P=0.001, respectively), independent of age, body mass index and serum total cholesterol (=0.77, P<0.001, R² of the overall model=0.79 and =0.70, P<0.005, R² of the overall model=0.69, respectively). Our data provide evidence suggesting that in young healthy men a higher submaximal and maximal aerobic exercise performance is associated with a greater FMD of peripheral conduit arteries.     

Comparison of clinical outcomes of Chinese men and women after coronary stenting for coronary artery disease：a multi-center retrospective analysis of 4,334 patients

The outcome differences between Chinese male and female patients within one-year follow-up after percutaneous coronary intervention（PCI） with stent remain unclear.The present study was aimed to compare clinical outcomes in such two populations.From May 1999 to December 2009,4,334 patients with acute myocardial infarction（MI）,unstable angina,stable angina,or silent ischemia,who underwent PCI,were registered at our centers.Among these,3,089 were men and 1,245 were women.We compared these groups with respect to the primary outcomes of MI and secondary outcomes including a composite of major adverse cardiac events（MACE） including cardiac death,MI,target lesion revascularization,target vessel revascularization（TVR）,stent thrombosis（ST）,definite ST and probable ST at one-year follow-up.Chinese male patients had a higher MACE rate（13%vs.10.7%,P =0.039）,mainly led by TVR（9.09%vs.6.98%,P=0.024） at one year,which was significantly different than female patients.Chinese male and female patients showed a significant difference on MACEs.However,there was no significant difference with respect to MI between these groups.     

Radial basis function neural network approach for the diagnosis of coronary artery disease based on the standard electrocardiogram exercise test

The purpose of the paper is the evaluation of a radial basis function neural network as a tool for computer aided coronary artery disease diagnosis based on the results of the traditional ECG exercise test. The research was performed using 776 data records from an exercise test (297 records from healthy patients and 479 from ill patients) confirmed by coronary arteriography results. Each record described the state of the patient, provided input data for the neural network, included the level and slope of an ST segment of a 12-lead ECG signal made at rest and after effort, heart rate, blood pressure, load during the test, and occurrence of coronary pain, coronary arteriography, correct output pattern for the neural network, and verified the existence (or not) of more than 50% stenosis of the particular coronary vessels. Radial basis function neural networks for coronary artery disease diagnosis were optimised by choosing the type of radial function, the method of training (setting the number of centres and their dimensions), and regularisation. The best network correctly recognised over 97% of cases from a 400-element test set, diagnosing not only the patients' condition (simple ‘sane-sick’ diagnosis), but also pointing out individual sick/stenosed vessels.     

Characteristics of young men with clustering risk factors for coronary heart disease: The cardiovascular risk in young finns study

The majority of coronary heart disease (CHD) arises from a population with only moderately elevated risk factor levels. This study addressed the issue of whether clustering of moderately adverse levels of serum low density lipoprotein cholesterol (LDL-C), serum high density lipoprotein cholesterol (HDL-C), and diastolic blood pressure (DBP) was detectable in children and young adults. Significant clustering of these factors was observed in young men (ages 18–24 years) (Observed/Expected [O/E] ratio = 1.5, p = 0.014), whereas in young women or children no clustering greater than due to chance was found. In males, clustering tended to increase with age. Compared to young women, young men had a higher relative intake of dietary fat, and smoked and used alcohol more often. Compared to men without risk factors, the men at risk were significantly more obese, consumed more dietary fat, and smoked more often. The highest degree of clustering was seen in the highest quartile for the subscapular skinfold thickness (O/E ratio = 2.4). In conclusion, high LDL-C, low HDL-C, and high DBP cluster in young adult males. The clear sex difference observed in clustering may be one of the causes for the susceptibility of adult men to CHD. Am. J. Hum. Biol. 9:565–571, 1997. © 1997 Wiley-Liss, Inc.     

Association of CD36 gene polymorphisms with echo- and electrocardiographic parameters in patients with early onset coronary artery disease

Introduction

CD36 plays an important role in long-chain fatty acid homeostasis in skeletal muscle and the myocardium. CD36 deficiency may lead to reduced myocardial uptake of long-chain fatty acid. Therefore, different mutations of the CD36 gene may contribute to the clinical heterogeneity of cardiac hypertrophy.

Material and methods

The objective of the study was to investigate whether there is an association between the sequence changes in CD36 and echocardiographic and electrocardiographic parameters in Caucasian patients with early onset coronary artery disease. The study group comprised 100 patients. Electrocardiography and echocardiography were performed in all patients. Amplicons of exons 4 to 6 including fragments of introns were studied using the denaturing high-performance liquid chromatography technique.

Results

IVS3-6TC (rs3173798) heterozygotes had impaired left ventricle diastolic function. 573GA heterozygotes (rs5956) had higher frequency of pseudonormal left ventricular diastolic function and it was confirmed by the increase in wave A’ in the tissue Doppler. 591AT genotype was associated with borderline higher posterior wall end-diastolic thickness and lower E/A ratio. These results are consistent with electrocardiography parameters which could reflect left ventricular hypertrophy (higher R_V5(6) and R_V5(6) + S_V1(2) parameters, depressed ST segments and tendency to longer Qtc II interval) in 591AT heterozygotes.

Conclusions

Detected variant alleles of CD36 may be associated with features of left ventricular hypertrophy and impaired diastolic function.     

Detection of coronary artery disease by means of exercise ECG in patients with aortic stenosis

In a preoperative evaluation, 35 consecutive patients with aortic stenosis were examined by means of exercise ECG, Doppler and direct manometric measurements of the pressure difference over the aortic valve (delta P) and angiocardiography. Coronary artery disease (CAD) was found in 43% of the patients. Those with CAD had a lower mean maximum physical performance expressed as a percentage of the normal value (Wmax%), larger ST depressions and a higher effort angina (EA) score at the exercise test than the non-CAD group. Mean delta P was equal in the two groups. A myocardial coronary obstruction score covariated positively with a coronary insufficiency index (CT index = 100 X STdepr/Wmax%) and the EA score. There was no correlation between delta P and the EA score or the CI index. A CI index less than 3 and an EA score less than 2 were found in 49% of the patients and excluded the presence of CAD with a predictive accuracy of 88%, a better diagnostic complement to coronary arteriography than a history of EA.     

Regional myocardial metabolism of high-energy phosphates during isometric exercise in patients with coronary artery disease

BACKGROUND. The maintenance of cellular levels of high-energy phosphates is required for myocardial function and preservation. In animals, severe myocardial ischemia is characterized by the rapid loss of phosphocreatine and a decrease in the ratio of phosphocreatine to ATP. METHODS. To determine whether ischemic metabolic changes are detectable in humans, we recorded spatially localized phosphorus-31 nuclear-magnetic-resonance (31P NMR) spectra from the anterior myocardium before, during, and after isometric hand-grip exercise. RESULTS. The mean (+/- SD) ratio of phosphocreatine to ATP in the left ventricular wall when subjects were at rest was 1.72 +/- 0.15 in normal subjects (n = 11) and 1.59 +/- 0.31 in patients with nonischemic heart disease (n = 9), and the ratio did not change during hand-grip exercise in either group. However, in patients with coronary heart disease and ischemia due to severe stenosis (greater than or equal to 70 percent) of the left anterior descending or left main coronary arteries (n = 16), the ratio decreased from 1.45 +/- 0.31 at rest to 0.91 +/- 0.24 during exercise (P less than 0.001) and recovered to 1.27 +/- 0.38 two minutes after exercise. Only three patients with coronary heart disease had clinical symptoms of ischemia during exercise. Repeat exercise testing in five patients after revascularization yielded values of 1.60 +/- 0.20 at rest and 1.62 +/- 0.18 during exercise (P not significant), as compared with 1.51 +/- 0.19 at rest and 1.02 +/- 0.26 during exercise before revascularization (P less than 0.02). CONCLUSIONS. The decrease in the ratio of phosphocreatine to ATP during hand-grip exercise in patients with myocardial ischemia reflects a transient imbalance between oxygen supply and demand in myocardium with compromised blood flow. Exercise testing with 31P NMR is a useful method of assessing the effect of ischemia on myocardial metabolism of high-energy phosphates and of monitoring the response to treatment.     

Effect of continuous and interval exercise training on the PETCO2 response during a graded exercise test in patients with coronary artery disease

OBJECTIVE:

The purpose of this study was to evaluate the following: 1) the effects of continuous exercise training and interval exercise training on the end-tidal carbon dioxide pressure (PETCO₂) response during a graded exercise test in patients with coronary artery disease; and 2) the effects of exercise training modalities on the association between PETCO₂ at the ventilatory anaerobic threshold (VAT) and indicators of ventilatory efficiency and cardiorespiratory fitness in patients with coronary artery disease.

METHODS:

Thirty-seven patients (59.7±1.7 years) with coronary artery disease were randomly divided into two groups: continuous exercise training (n = 20) and interval exercise training (n = 17). All patients performed a graded exercise test with respiratory gas analysis before and after three months of the exercise training program to determine the VAT, respiratory compensation point (RCP) and peak oxygen consumption.

RESULTS:

After the interventions, both groups exhibited increased cardiorespiratory fitness. Indeed, the continuous exercise and interval exercise training groups demonstrated increases in both ventilatory efficiency and PETCO₂ values at VAT, RCP, and peak of exercise. Significant associations were observed in both groups: 1) continuous exercise training (PETCO₂VAT and cardiorespiratory fitness r = 0.49; PETCO₂VAT and ventilatory efficiency r = -0.80) and 2) interval exercise training (PETCO₂VAT and cardiorespiratory fitness r = 0.39; PETCO₂VAT and ventilatory efficiency r = -0.45).

CONCLUSIONS:

Both exercise training modalities showed similar increases in PETCO₂ levels during a graded exercise test in patients with coronary artery disease, which may be associated with an improvement in ventilatory efficiency and cardiorespiratory fitness.     

Electron beam computed tomography for assessment of coronary artery disease in HIV-infected men receiving antiretroviral therapy

Hyperlipidemia has been seen in patients receiving protease inhibitor-based antiretroviral therapy, prompting concern that such patients are at risk for accelerated coronary artery disease (CAD). To assess the risk of CAD in antiretroviral-treated HIV-infected men, we quantified coronary artery calcium (CAC), a sensitive and established marker of subclinical CAD, using electron beam computed tomography (EBCT) of coronary vessels. Sixty HIV-infected men who met the following criteria (cases) were enrolled in the study: age of 40 years or older; naive to antiretroviral therapy or use of a stable antiretroviral regimen for >or=6 months (mean duration, 25.9 months; 41 patients were receiving protease inhibitor therapy); and no known CAD or no use of lipid-lowering agents. EBCT-derived CAC scores, serum lipid levels, history of antiretroviral therapy, and risk factors for CAD were obtained. Each case was compared with three age-, sex-, and race-matched HIV-negative controls randomly selected from a database including >9000 patients who had undergone EBCT. We determined differences in the proportion of cases and controls with CAC scores of >0 (detectable calcium) and clinically significant CAC for age range. There were no statistically significant differences between the number of cases and controls with detectable CAC (33% and 39%, respectively) and clinically significant CAC (18% and 17%, respectively). This study suggests that the rate of coronary atherosclerosis among HIV-infected patients who receive short-term antiretroviral therapy with or without protease inhibitors is not higher than that among age-, sex-, and race-matched HIV-negative controls. These results need to be confirmed in larger long-term studies, with controls well matched for coronary risk factors.