Maximal ST-segment Depression Research Articles

403 ECG EXERCISE STRESS TEST PREDICTORS OF LEFT MAIN CORONARY ARTERY DISEASE

Abstract Background Left main coronary artery disease (LMCAD) heavily affects prognosis of patients with suspected CAD. Thus, its identification/exclusion is an important step in the assessment of these patients. Although being the gold standard to identify LMCAD, invasive coronary angiography (ICA) is burdened by some risks, while coronary computed tomography angiography (CCTA) has still limited availability, quite high costs and associated radiologic risks. In the past decades, several studies demonstrated the utility of ECG exercise stress test (EST) for the identification of LM disease in patients with suspected CAD. However, the pre-test probability of CAD of subjects undergoing EST has significantly changed in the last decades. Accordingly, in this study we aimed to assess the predictive value of EST for the presence/absence of LMCAD in a contemporary population of patients with suspected CAD. Methods We retrospectively enrolled 495 consecutive patients, referred to our Center between years 2018 and 2021 because of suspected CAD, who underwent both an EST (standard treadmill Bruce protocol) and ICA (within 12 months of the EST). Patients with a history of coronary artery bypass surgery were excluded. Results Overall, 24 patients (4.8%) were found to have LMCAD at ICA. Among clinical variables, only male gender (p=0.025) and smoking (p=0.003) were associated with LMCAD. A number of ECG leads with EST-induced ST-segment depression (STD) ≥5 and a maximal STD ≥2 mm were more frequently found in patients with, compared to those without LMCAD (29.2 vs 9.8%, p=0.003; and 58.3 vs 24.8%, p<0.001, respectively). No other EST variable was associated with LMCAD, including ST-segment elevation in lead aVR (4.2 vs. 2.6% in the 2 groups, respectively, p=0.63). On the other hand, among the 206 patients (41.6% of the population) who achieved 85% of maximal heart rate predicted for age and had ST-segment depression < 2mm, LMCAD was present in 1.9% only. Conclusions Our data indicate that EST continues to be a valuable tool for predicting the presence/absence of LMCAD in contemporary populations of patients with suspected coronary artery disease.

Exercise test predictors of severe coronary artery disease: Role of ST‐segment elevation in lead aVR

The role of exercise stress test (EST)-induced ST-segment elevation (STE) in electrocardiographic lead aVR in predicting severe coronary artery disease (CAD) is controversial. Assessment of lead aVR during EST can be helpful to identify patients with severe CAD. We performed maximal EST in 200 patients undergoing coronary angiography for suspect of CAD. Four angiographic findings of severe CAD were considered: (1) left main (LM) disease; (2) LM or equivalent LM (LM/EQLM) disease; (3) LM or proximal left anterior descending (LAD) artery (LM/proxLAD) disease; and (4) LM or 3-vessel (LM/3V) disease. LM, LM/EQLM, LM/proxLAD, and LM/3V disease were shown in 6 (3%), 13 (6.5%), 33 (16.5%), and 27 (13.5%) patients, respectively. EST-induced STE in aVR occurred in 41 patients (20.5%). ST-segment depression (STD) in ≥5 leads was the only predictor of LM stenosis (odds ratio [OR]: 6.18, 95% confidence interval [CI]: 1.19-32.2, P = 0.03) and the most significant variable associated with LM/proxLAD stenosis (OR: 4.73, 95% CI: 2.0-11.2, P = 0.0001); maximal STD ≥3 mm was the most significant variable associated with LM/EQLM (OR: 7.58, 95% CI: 2.31-24.9, P = 0.001) and LM/3V (OR: 3.86, 95% CI: 1.47-10.1, P = 0.006) CAD. EST-induced STE in aVR was associated with LM/proxLAD disease only (OR: 3.23, 95% CI: 1.44-7.24, P = 0.004). At multivariate analysis, STD in ≥5 leads was the only independent predictor of LM/proxLAD disease (OR: 3.99, 95% CI: 1.58-10.1, P = 0.003). EST-induced STE in lead aVR does not significantly increase the prediction of severe CAD compared with severity and extension of STD as assessed in the other electrocardiographic leads.

Exercise-Induced Ischemic Preconditioning and the Potential Application to Cardiac Rehabilitation

Exercise-induced ischemic preconditioning (IPC) can be assessed by the results of the second of sequential exercise tests. Exercise-induced IPC is quantified by using the time to 1-mm ST-segment depression, the rate-pressure product at 1-mm ST-segment depression, the maximal ST-segment depression, and the rate-pressure product at the peak of exercise. Few studies reported whether exercise-induced IPC could be used in cardiovascular rehabilitation. A systematic review of the literature limited to human studies was performed using electronic databases, and the main key words were ischemic preconditioning, warm-up phenomenon, and exercise. After careful review, 38 articles were included in the systematic review. This review summarizes the molecular pathways of IPC and describes the first window of protection induced by sequential exercise tests, as well as the effect of medication on exercise-induced IPC. A section on the exercise protocol, mode of exercise, and intensity provides understanding as to what is needed for clinicians to induce IPC with sequential stress tests. The final section of the review is a discussion of the potential use of exercise-induced IPC in a cardiovascular rehabilitation setting. Even if exercise-induced IPC is a well-documented phenomenon, additional studies are needed in order to more fully understand its use in rehabilitation.

Vitamin D replacement therapy in patients with cardiac syndrome X.

The aim of present study was to assess whether vitamin D, with proven beneficial effects on the cardiovascular system, has any effect on angina and exercise-induced ischemia in patients with cardiac syndrome X and low serum vitamin D. Patients with cardiac syndrome X and low serum vitamin D3 were studied before and after treatment with an intramuscular injection of vitamin D3 (300,000 units, every other week for 2 months). We determined the angina episode (per day) and several indices of exercise capacity. At the end of the treatment course (75±6 day), a significant increase of serum vitamin D3 occurred and was within the normal range (45±8 ng/ml) and the frequency of angina improved significantly (p=0.003). Exercise duration and maximal work capacity increased significantly (p<0.001). Maximal ST-segment depression (mm) decreased significantly (p=0.001). The calculated Duck treadmill score improved significantly (p=0.001). Our findings show that vitamin D replacement therapy in patients with cardiac syndrome X and vitamin D deficiency dramatically improves symptoms and signs of ischemia.

Psychological and Physiological Predictors of Angina During Exercise-Induced Ischemia in Patients With Coronary Artery Disease

This study compares sensory-biological, cognitive-emotional, and cognitive-interpretational factors in predicting angina on an exercise treadmill test (ETT). A total of 163 patients with ETT-induced ischemia and coronary artery disease in the National Heart, Lung, and Blood Institute Psychophysiological Investigations of Myocardial Ischemia study were given an ETT, during which 79 patients reported angina. We assessed the following as potential predictors of self-reported anginal pain: sensory-biological factors (β-endorphin reactivity, hot pain threshold, and maximal ST-segment depression), cognitive-emotional factors (negative affect and symptom perception), and cognitive-interpretational factors (self-reported history of exercise-induced angina). Models were covariate adjusted with predictors examined individually and as part of component blocks. Logistic regression revealed that history of angina (odds ratio [OR] = 17.41, 95% confidence interval = 7.16-42.34) and negative affect (OR = 1.65, 95% confidence interval = 1.17-2.34), but not maximal ST-segment depression, hot pain threshold, β-endorphin reactivity, or symptom perception, were significant predictors of angina on the ETT. The sensory-biological block was not significantly predictive of anginal pain (χ(2)block = 5.15, p = .741). However, the cognitive-emotional block (χ(2)block = 11.19, p = .004) and history of angina (cognitive-interpretation; χ(2)block = 54.87, p < .001) were predictive of ETT angina. A model including all variables revealed that only history of angina was predictive of ETT pain (OR = 16.39, p < .001), although negative affect approached significance (OR = 1.45, p = .07). In patients with ischemia, cognitive-emotional and cognitive-interpretational factors are important predictors of exercise angina.

Correlation of Angiographic Findings between Right (V1 to V3) versus left (V4 to V6) Precordial ST Segment Depression in Acute Inferior Myocardial Infarction

The initial ECG in patients with acute inferior MI may have a great value to identify the subgroup of patients who are at high risk by predicting multivessel coronary artery disease (CAD). These patients, therefore, may benefit from a more invasive approach. ST segment depression in leads V4 to V6 but not V1 to V3 confers a greater likelihood of multivessel CAD. The aim of the study to correlate between ST-depression in ECG on admission &amp; severity of coronary lesion in angiogram in acute inferior MI. This study was undertaken in the department of cardiology of Bangabandhu Sheikh Mujib Medical University and in Ibrahim Cardiac Hospital &amp; Research Institute from March 2009 to October 2010. Patients (total 93) of acute inferior MI, who were presented within 12hrs of onset of symptoms and got intravenous thrombolytics were divided into three groups after initial ECG, group A-without precordial ST-segment depression, group B- maximal precordial STsegment depression in leads V1–V3 and group C- maximal precordial ST-segment depression in leads V4– V6.CAG was done within six weeks of MI and findings of CAG were compared among the groups. Age, sex, distribution of risk factors were identical among the groups. Significant number (53.8%) of patients in group C had a lower ejection fraction (LVEF&lt; 50%) than group B (30%) and group A (10.8%) (p=0.001). Patients of group C more often had double vessel disease (38.5% p=0.007) and triple vessel disease (30.8%) (p=0.014). In contrast, single vessel disease was more common in group B (80%) (p=0.001). Involvement of LAD was also significantly higher in group-C (73.1% p= 0.001). Left precordial ST depression (lead V4-V6) correlates with multivessel CAD, a trend toward a higher rate of LAD artery disease and is associate with LV dysfunction. DOI: http://dx.doi.org/10.3329/uhj.v7i2.10839 University Heart. Journal Vol. 7, No. 2, July 2011

Reducing Personal Exposure to Particulate Air Pollution Improves Cardiovascular Health in Patients with Coronary Heart Disease

Background: Air pollution exposure increases cardiovascular morbidity and mortality and is a major global public health concern.Objectives: We investigated the benefits of reducing personal exposure to urban air pollution in patients with coronary heart disease.Methods: In an open randomized crossover trial, 98 patients with coronary heart disease walked on a predefined route in central Beijing, China, under different conditions: once while using a highly efficient face mask, and once while not using the mask. Symptoms, exercise, personal air pollution exposure, blood pressure, heart rate, and 12-lead electrocardiography were monitored throughout the 24-hr study period.Results: Ambient air pollutants were dominated by fine and ultrafine particulate matter (PM) that was present at high levels [74 μg/m3 for PM2.5 (PM with aerodynamic diamater <2.5 µm)]. Consistent with traffic-derived sources, this PM contained organic carbon and polycyclic aromatic hydrocarbons and was highly oxidizing, generating large amounts of free radicals. The face mask was well tolerated, and its use was associated with decreased self-reported symptoms and reduced maximal ST segment depression (–142 vs. –156 μV, p = 0.046) over the 24-hr period. When the face mask was used during the prescribed walk, mean arterial pressure was lower (93 ± 10 vs. 96 ± 10 mmHg, p = 0.025) and heart rate variability increased (high-frequency power: 54 vs. 40 msec2, p = 0.005; high-frequency normalized power: 23.5 vs. 20.5 msec, p = 0.001; root mean square successive differences: 16.7 vs. 14.8 msec, p = 0.007). However, mask use did not appear to influence heart rate or energy expenditure.Conclusions: Reducing personal exposure to air pollution using a highly efficient face mask appeared to reduce symptoms and improve a range of cardiovascular health measures in patients with coronary heart disease. Such interventions to reduce personal exposure to PM air pollution have the potential to reduce the incidence of cardiovascular events in this highly susceptible population.

Effectiveness of the fixed-dose combination therapy with perindopril and amlodipine in coronary heart disease patients after coronary artery bypass graft surgery

Aim.To study the effectiveness of the fixed-dose combination therapy with perindopril and amlodipine (Prestance 5/5 mg/d) in coronary heart disease (CHD) patients after coronary artery bypass graft (CABG) surgery.Material and methods.The clinical trial included 65 patients (37 men, 28 women aged 45-68 years; mean age 56,3±3,5 years) after CABG. All patients were randomised into two groups: the control group (CG; n=35) and the main group (MG; n=30). Both groups received antiplatelet agents and statins, while the MG patients additionally received Prestance (5/5 mg/d). Prestance therapy started three-four weeks after CABG and lasted for four months. All participants underwent 24-hour monitoring of ECG and blood pressure (BP), Doppler echocardiography, and Doppler ultrasound of brachial and common carotid arteries.Results.Compared to the CG, the MG demonstrated decreased incidence of pain and painless ischemia episodes, reduced maximal ST segment depression and its total duration, and increased rate threshold of myocardial ischemia. In addition, Prestance therapy was associated with improved systolic and diastolic heart function and significantly improved endothelium-dependent vasodilatation. In patients with normal BP, Prestance (5/5 mg/d) did not cause hypotension, but reduced excessive BP variability. In the MG, acute coronary syndrome (ACS) was registered in 1 individual (3,3 %), while in the CG, it was registered in 4 patients (11.4 %), and in 3 cases, coronary artery stenting was performed.Conclusion.In patients with normal BP, Prestance (5/5 mg/d) therapy in the early post-CABG period had a pronounced anti-ischemic, cardio- and vasoprotective effects, and also prevented excessive BP variability.

051 Reducing particulate air pollution exposure in patients with coronary heart disease: improved cardiovascular health

Introduction Particulate air pollution is a major public health concern and is associated with cardiovascular disease. In healthy volunteers, reducing particulate air pollution exposure attenuates exercise-induced increases in blood pressure and improves heart rate variability. In this study, we investigated the benefit of reducing exposure in patients with coronary heart disease. Methods In an open-label randomised crossover trial, 98 patients with coronary heart disease walked on a predefined city centre route in Beijing in the presence and absence of a highly efficient facemask. Personal exposure to air pollution and exercise was assessed continuously using portable monitors and GPS tracking respectively. Blood pressure was measured using ambulatory blood pressure monitoring. Continuous 12-lead electrocardiography was carried out using a Holter monitor. Subjects9 symptoms were assessed using a simple questionnaire. Results The mask intervention was well tolerated and reduced general symptoms, perceived effort of work and perception of pollution (p 3 ; PM 2.5 ) and particle number (4.19±1.29 vs 4.39±1.45×10 4 particles/cm 3 ) were slightly lower during the mask visit, but based on efficacy studies, we predict the mask reduced the exposure further to 2 μg/m 3 and 1200 particles/cm 3 respectively. During the 2-h walk, exercise performed was identical on both visits. When subjects wore a facemask, mean arterial pressure was lower (93±10 vs 96±10 mm Hg; p=0.025) and heart rate was similar (p>0.05). During the 2-h walk, heart rate variability was increased (HF-power 54 (27 to 108) vs 40 (20 to 69) ms 2 , p=0.005; HF/LF ratio 0.418 (0.258 to 0.712) vs 0.328 (0.207 to 0.573), p=0.004; RMSSD 16.7 (13.2 to 22.5) vs 14.8 (10.9 to 19.6) ms, p=0.007) when a facemask was worn. There were no differences in overall 24-h blood pressure, heart rate or heart rate variability. Maximal ST segment depression throughout the 24-h period was reduced when subjects wore a mask (−142 (−179 to −110) vs −156 (−202 to −123) μV; p=0.046) although there was no difference in the frequency of ST segment depression (>1 mm) episodes or symptoms of angina. Conclusions In patients with coronary heart disease, wearing a facemask reduces symptoms and is associated with objective improvements in myocardial ischaemia, blood pressure and heart rate variability. This simple well-tolerated intervention has the potential to reduce the incidence of cardiovascular events in patients with coronary heart disease living in industrialised or urban environments.

Ambulatory recorded ST segment depression on ECG is associated with lower cognitive function in healthy elderly men.

ST segment depression (STDE) has been found to be associated with cardiovascular disease in the elderly. Studies of the relation of ambulatory STDE to cognitive function in elderly persons aged 80 years or above is lacking. To study the association between STDE and cognition. A cross-sectional cohort study of 88 81-year-old men from the population study "Men born in 1914" investigated in an outpatient research clinic. Measurements included ambulatory 24-hour electrocardiogram (ECG) monitoring and a cognitive test battery of six tests. Proportion of lower cognitive function was calculated for each test in relation to STDE during the day and at night-time. Fifty-eight percent of the men had STDE and a higher proportion with low visuospatial cognitive function was found among those with STDE compared to the others (84% vs 59%; p = 0.014). A significant trend was noted for subjects without STDE compared to STDE night-time less than 60 minutes and night-time more than 60 minutes for spatial and verbal cognitive functions (p = 0.022). No trends were noted for STDE daytime. Maximal STDE during night showed similar association to spatial function (Benton Visual Retention test, r = -0.26; p = 0.028). Even when seven subjects with a history of stroke were excluded, the occurrence of STDE was associated to lower visuospatial cognitive function compared to those without STDE (87% vs 57%; p = 0.004). ST segment depression on ECG is common among elderly men and might be a vascular risk factor for cognitive deterioration.

Interrelation of ST-segment depression during bicycle ergometry and extent of myocardial ischaemia by myocardial perfusion SPECT

The aim of this study was to compare ST-segment depression (STD) during bicycle ergometry and extent of myocardial ischaemia assessed by myocardial perfusion SPECT (MPS) in a large patient cohort. Consecutive patients (n = 955) referred for MPS with bicycle ergometry and interpretable stress ECG were evaluated with respect to ECG and MPS findings of ischaemia. The maximal STD was recorded and exercise ECG was considered ischaemic if STD was horizontal or downsloping (>or=1 mm). MPS was interpreted using a 20-segment model with a scale of 0 to 4. A summed stress (SSS), summed rest (SRS) and summed difference score (SDS = SSS-SRS, e.g. extent of ischaemia) were derived. Ischaemia was defined as an SDS >or= 2. An exercise-induced STD was present in 215 patients (22%) and myocardial ischaemia on MPS was present in 366 patients (38%). The extent of ST-segment depression and the number of ECG leads with significant STD were each strongly and significantly associated with increasing severity of ischaemia and the number of coronary territories involved (p < 0.01 for all correlations). These data demonstrate a strong correlation between the extent of STD, number of ischaemic leads and severity of myocardial ischaemia as assessed by MPS during bicycle ergometry.

Effect of Low Doses of Alcohol on the Warm-Up Phenomenon in Patients With Stable Angina Pectoris

Experimental studies suggest that alcohol may have protective effects similar to that of ischemic preconditioning (IPC). The acute effects of alcohol on IPC in humans, however, are poorly known. In this study, we assessed the effect of alcohol administration on the warm-up phenomenon, as an expression of IPC, in patients with stable coronary artery disease (CAD). We randomized 45 stable CAD patients with positive (ST-segment depression > or =1 mm) exercise stress test to 1 of 3 groups of 15 patients each: (1) group 1 = 60 cc of gin (18.5 g of ethanol); (2) group 2 = 180 cc of red wine (18.9 g of ethanol); and (3) group 3 = placebo (120 cc of water). A first exercise test was performed 15 minutes after beverage administration. In those with a positive exercise test (13, 14, and 14 patients in the gin, wine, and placebo groups, respectively), a second exercise test was performed 15 minutes after the end of the first one. On the first test, there were no differences among groups in rate pressure product and time of exercise at 1-mm ST-segment depression, as well as in maximal ST segment depression. Furthermore, an improvement of the ischemic exercise variables was observed in each group, without any statistically significant differences among them. In conclusion, our data show that, in stable CAD patients, the acute intake of low doses of alcohol does not significantly influence IPC, as expressed by the warm-up phenomenon on exercise stress testing.

Effects of Metformin on Microvascular Function and Exercise Tolerance in Women With Angina and Normal Coronary Arteries: A Randomized, Double-Blind, Placebo-Controlled Study

This study sought to determine whether metformin improves vascular function or myocardial ischemia in nondiabetic subjects. Metformin prevents diabetes and may reduce coronary events in patients with diabetes, but effects on microvascular function and angina are not clear. We conducted an 8-week double-blind, randomized, placebo-controlled study of metformin 500 mg twice a day in 33 nondiabetic women with a prior history of normal coronary angiography but two consecutive positive (ST-segment depression > or =1 mm) exercise tolerance tests. All parameters were measured at baseline and at 8 weeks, together with an in vivo assessment of forearm (skin) microvascular function using laser Doppler imaging combined with iontophoresis. In comparison with placebo (n = 17), metformin recipients (n = 16) showed significant reductions in weight and in homeostatic model assessment for insulin resistance (p < 0.05, intention to treat). Endothelium-dependent microvascular responses improved significantly with metformin (2-way repeated analysis of variance, p = 0.0003), but responses with placebo were unchanged (p = 0.50). A comparison of change in acetylcholine responses between metformin and placebo recipients was significant, whether analyzed by a 2-way analysis of variance (p < 0.0001) or change in area under curves (mean change +392 perfusion units, 95% confidence interval [CI] 20 to 764). Endothelium-independent responses were not altered. Maximal ST-segment depression (-0.84 mm, 95% CI -1.49 to -0.20, p = 0.013), Duke score (6.1 U, 95% CI 1.8 to 10.5, p = 0.008), and chest pain incidence (-0.11 episodes/day, 95% CI -0.22 to 0.00, p = 0.056) improved in metformin relative to placebo recipients. Metformin may improve vascular function and decrease myocardial ischemia in nondiabetic women with chest pain and angiographically normal coronary arteries. Larger controlled trials of longer duration are warranted.

Exercise stress testing before and after successful multivessel percutaneous transluminal coronary angioplasty

Controversy exists regarding the diagnostic accuracy, optimal technique, and timing of exercise testing after percutaneous coronary intervention. The objectives of the present study were to analyze variables and the power of exercise testing to predict restenosis or a new lesion, 6 months after the procedure. Eight-four coronary multi-artery diseased patients with preserved ventricular function were studied (66 males, mean age of all patients: 59 +/- 10 years). All underwent coronary angiography and exercise testing with the Bruce protocol, before and 6 months after percutaneous coronary intervention. The following parameters were measured: heart rate, blood pressure, rate-pressure product (heart rate x systolic blood pressure), presence of angina, maximal ST-segment depression, and exercise duration. On average, 2.33 lesions/patient were treated and restenosis or progression of disease occurred in 46 (55%) patients. Significant increases in systolic blood pressure (P = 0.022), rate-pressure product (P = 0.045) and exercise duration (P = 0.003) were detected after the procedure. Twenty-seven (32%) patients presented angina during the exercise test before the procedure and 16 (19%) after the procedure. The exercise test for the detection of restenosis or new lesion presented 61% sensitivity, 63% specificity, 62% accuracy, and 67 and 57% positive and negative predictive values, respectively. In patients without restenosis, the exercise duration after percutaneous coronary intervention was significantly longer (460 +/- 154 vs 381 +/- 145 s, P = 0.008). Only the exercise duration permitted us to identify patients with and without restenosis or a new lesion.

Delayed Preconditioning-Mimetic Actions of Nitroglycerin in Patients Undergoing Exercise Tolerance Tests

Nitroglycerin (NTG) induces delayed preconditioning (PC)-mimetic effects in animal models and in humans during coronary angioplasty. We tested the hypothesis that NTG mitigates ischemia and enhances functional capacity during an exercise tolerance test (ETT) in patients with coronary artery disease. Twenty-eight patients with stable angina and ischemia documented by a stress test were randomized in a double-masked, crossover design to receive a titrated intravenous infusion of NTG or normal saline over 4 hours. At 24 to 28 hours after study medication infusion, each patient underwent 2 ETTs separated by a 1-week washout period. Compared with control patients, pretreatment with NTG was associated with a dose-dependent increase in exercise duration averaging 40 seconds (412+/-19 versus 372+/-24 seconds, P=0.014) and an improvement in ECG manifestations of ischemia, as shown by a decrease in maximal ST-segment depression (1.84+/-0.14 versus 1.63+/-0.13 mm, P=0.011), sum of ST-segment depressions in 12 leads (7.64+/-1.01 versus 6.61+/-0.83 mm, P=0.027), and time to resolution of ST-segment depression (229+/-30 versus 207+/-28 s, P=0.018). These benefits occurred despite an increase in myocardial workload after NTG, as indicated by a higher peak rate-pressure product (24 492+/-1054 versus 22 536+/-1019 mm Hg/min, P=0.015). NTG produces a late PC-mimetic effect that mitigates the ECG manifestations of ischemia during exercise and improves exercise capacity. To our knowledge, this is the first study to demonstrate that NTG can alleviate exercise-induced ischemia 24 hours after its administration, long after the hemodynamic effects have subsided. The finding that nitrate-induced late PC ameliorates a common manifestation of coronary artery disease has potentially significant implications for the management of this disorder and for the design of clinical trials.

Comparison of the effects of trimetazidine and diltiazem on exercise performance in patients with coronary heart disease. The Turkish trimetazidine study (TTS)

Objective — A multicentre, double-blind comparative study was performed to compare the effects of trimetazidine with diltiazem on exercise performance in patients with stable angina pectoris.Methods and results — A total of 116 male patients with documented coronary artery disease at 11 centres were randomized into trimetazidine and diltiazem groups both including 58 men (mean age 55.1 ± 8.6 years and 54.9 ± 6.6 years, respectively) in a prospective, multicentre, double-blind active treatment trial.The study consisted of a two-week placebo washout period and a four-week active treatment phase. Clinical examinations and exercise tests were performed at the beginning (D0) and at the end (D28) of the active treatment. Laboratory investigations were also performed at the beginning of the washout period (D-14) and at D28. Holter recordings were done in the mid of the washout period (D-7) and D28. Both trimetazidine and diltiazem decreased the number of anginal attacks per week (p < 0.0001 for both drugs) and weekly nitrate consumption (p = 0.0008 and p < 0.0001, respectively). Both trimetazidine and diltiazem improved the recovery of anginal pain (p = 0.0188 and p = 0.0079, respectively) and maximal ST-segment depression (p = 0.0134 and p = 0.0214, respectively) but none of the drugs significantly changed the time to 1 mm ST-segment depression and ST recovery time on exercise test. Diltiazem caused a slight prolongation of PR and QRS durations (p = 0.039) on ambulatory ECG whereas trimetazidine did not change these parameters significantly.Conclusion — This study suggests that trimetazidine is an effective and safe alternative for diltiazem in the treatment of patients with stable angina pectoris. Although several other trials have shown that this drug can be used in combination with other antianginal drugs or instead of beta blockers or nifedipine in the symptomatic treatment of stable anginal syndromes, this study suggests that trimetazidine can be used instead of diltiazem, a well-known powerful antianginal drug.

ST-depression with negative T waves in leads V4-V5--a marker of severe coronary artery disease in non-ST elevation acute coronary syndrome: a prospective study of Angina at rest, with troponin, clinical, electrocardiographic, and angiographic correlation.

The significance of ST-segment depression in acute coronary syndrome has been the subject of debate for many decades. Studies indicate that different manifestations of ST/T changes may have significantly different prognostic implications. We studied the correlation of ST/T changes in 12-lead electrocardiography recorded during pain, to clinical and angiographic findings and in-hospital prognosis, in patients with non-ST-elevation acute coronary syndrome and elevated troponin levels. Fifty consecutive patients could be differentiated into two groups: (1) 25 patients with ST-segment depression and a negative T wave maximally in leads V4-5, (2) 25 patients with ST-segment depression and a positive T wave in the precordial lead with maximal ST-segment depression. Patients in group I had significantly more often left main or left main equivalent coronary artery disease; 76% versus 8% (P < 0.001), heart failure; 40% versus 4% (P = 0.005), and higher in-hospital mortality; 24% versus 0% (P = 0.02), than patients in group II. The troponin levels did not differ significantly between the groups. In patients with non-ST-elevation acute coronary syndrome and elevated troponin levels two subgroups could be identified. Transient ST-segment depression and a negative T wave maximally in leads V4-5 during anginal pain predicts left main, left main equivalent, or severe three-vessel coronary artery disease with high sensitivity and specificity. In patients with ST-segment depression and a positive T wave, there is a high probability of one-vessel disease.

Effect of homocysteine-lowering therapy on vascular endothelial function and exercise performance in coronary patients with hyperhomocysteinaemia

Objective — This study was performed to determine the effect of homocysteine-lowering therapy (HLT) on endothelium-dependent vasodilation (EDD) and exercise performance in patients with coronary artery disease.Methods and Results — Among the patients who were on the waiting list for coronary intervention, 26 male patients (plasma homocysteine (Hcy) levels >15 mol/l) who had a focal stenosis of at least 70% in the left anterior descending artery were included in the study.The patients were matched to receive HLT (n = 15; 0.4 mg of folic acid, 2 mg vitamin B6 and 6 g of vitamin B12) or placebo (n = 11) until the coronary intervention was performed (mean 3.8±0.9 weeks). Brachial artery vasomotion test and treadmill stress testing were performed at baseline and 4 weeks after HLT before the time of coronary intervention in each patient. Hcy levels were found to be decreased significantly after HLT compared to baseline (23.4±6 vs. 11.3±4 mol/l; p<0.001) whereas placebo had no effect. HLT but not placebo produced a marked improvement in EDD, from 3.9±1.1% to 9.4±2.3% (p<0.0001). Endothelium-independent nitroglycerin-induced dilation was similar in the HLT and placebo groups compared with the baseline. In the exercise testing, HLT resulted in a significant improvement in exercise duration and reduction in the amount of maximal ST-segment depression, (from 6.5±2 to 6.9±2 min, p = 0.02 and from 1.2±0.7 to 0.8±0.5 mm, p = 0.01, respectively) whereas placebo did not.Conclusion — Lowering Hcy levels improves EDD and exercise performance while reducing the exercise-induced myocardial ischaemia in patients with coronary heart disease and hyperhomocysteinaemia.

Beneficial effects of betaxolol, a selective antagonist of beta-1 adrenoceptors, on exercise-induced myocardial ischemia in patients with coronary vasospasm

Although beta-blockers can not be used for the treatment of vasospastic angina, the effect of beta-blockers with vasorelaxant property on coronary vasospasm remains uncertain. In this study, we evaluated the effect of betaxolol, a new beta-blocker with calcium antagonistic property, as an additional therapy on vasospastic angina (VSA) with anginal attacks on effort. We enrolled 12 patients with VSA and anginal attacks with ST segment depression during exercise stress test. All patients received 1.25–5 mg of betaxolol for 3 months. Treadmill exercise stress test and adenosine triphosphate stress thallium-201 myocardial scintigraphy were performed before and 3 months after the onset of the betaxolol treatment. The other drugs including calcium antagonists, nitrates and nicorandil were continued. No patients experienced the exacerbation of angina during the betaxolol treatment. Exercise time to chest pain (317.5±72.1–454.2±75.5 s, P<0.01) and maximal ST segment depression (1.67±0.67–1.16±0.46 mm, P<0.01) obtained by exercise stress test, the defect score (8.6±2.7–5.3±2.1, P<0.01), the extent score (14.8±5.8–8.8±4.6%, P<0.01), the severity score (17.5±7.3–11.3±5.2, P<0.01) and washout rate (31.4±5.6–37.6±5.0%, P<0.01) obtained by the scintigraphy were improved by betaxolol. Our results suggest that betaxolol increases regional myocardial blood flow and improves exercise capacity in patients with VSA. Betaxolol may become a drug for a new potential therapy for VSA.

Effect of nipradilol on silent myocardial ischemia and heart rate variability in chronic stable angina.

Silent myocardial ischemic episodes as well as decreased heart rate variability (HRV) indices are associated with an unfavorable outcome in patients with coronary artery disease. Nipradilol, which is a nonselective beta-adrenergic and nitrate-like vasodilator anti-anginal agent developed in Japan, may ameliorate silent myocardial ischemia, while it also improves exercise tolerance and HRV indices in patients with chronic stable angina. To investigate the effect of nipradilol (6 mg daily) on silent myocardial ischemic episodes and HRV indices, and to study its effect on the relationship between them, 24 patients with chronic stable angina underwent exercise treadmill testing and a 24-hour ambulatory electrocardiogram (ECG). The study protocol utilized a single blind, 4-week placebo-controlled design. The HRV indices from ambulatory ECG included mean RR (ms), SDNN (ms), SDANN (ms), SD (ms), rMSSD (ms), pNN50 (%); frequency analysis of HRV consisted of total (ms, 0.01-1.00 Hz), low (ms, 0.04-0.15 Hz) and high (ms, 0.15-0.40 Hz) components. Nipradilol significantly decreased the mean heart rate at submaximal and maximal exercise and the mean pressure rate product at submaximal and maximal exercise. It significantly improved exercise-induced maximal ST segment depression from -1.7 +/- 0.6 mm to -1.1 +/- 0.7 mm (p < 0.05). Silent myocardial ischemic episodes recorded during the 24-hour ambulatory ECG significantly decreased after nipradilol administration. Nipradilol also significantly influenced several HRV indices as well as the relationship between silent myocardial ischemic episodes and the HRV indices. Nipradilol significantly increased SD, rMSSD, pNN50, total spectra, low frequency spectra and high frequency spectra. In addition, nipradilol significantly decreased the LF/HF ratio from 1.7 (1.5-2.0) to 1.5 (1.3-1.8). These effects of nipradilol on HRV indices concomitantly occurred with the reduction in silent myocardial ischemic episodes. Nipradilol was found to effectively improve the episodes of silent myocardial ischemia as well as exercise-induced ischemia probably due to its beta-blocking properties and not nitrate-like actions. In addition, nipradilol also had a favorable effect on the HRV indices.