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Background: Ischemic preconditioning (IP) is a powerful cellular protection mechanism. The cellular pathways underlying IP are extremely complex and involve the participation of cell triggers, intracellular signaling pathways, and end-effectors. Experimental studies have shown that sodium-glucose transport protein 2 (SGLT2) inhibitors promote activation of 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK), the main regulator of adenosine 5'-triphosphate homeostasis and energy metabolism in the body. Despite its cardioprotective profile demonstrated by numerous clinical trials, the results of studies on the action of SGLT2 inhibitors in IP are scarce. This study will investigate the effects of dapagliflozin on IP in patients with coronary artery disease (CAD). Methods: The study will include 50 patients with multivessel CAD, ischemia documented by stress testing, and preserved left ventricular ejection fraction (LVEF). Patients will undergo four exercise tests, the first two with a time interval of 30 min between them after washout of cardiovascular or hypoglycemic medications and the last two after 7 days of dapagliflozin 10 mg once a day, also with a time interval of 30 min between them. Discussion: The role of SGLT2 inhibitors on IP is not clearly established. Several clinical trials have shown that SGLT2 inhibitors reduce the occurrence cardiovascular events, notably heart failure. However, such studies have not shown beneficial metabolic effects of SGLT2 inhibitors, such as reducing myocardial infarction or stroke. On the other hand, experimental studies with animal models have shown the beneficial effects of SGLT2 inhibitors on IP, a mechanism that confers cardiac and vascular protection from subsequent ischemia-reperfusion (IR) injury. This is the first clinical study to evaluate the effects of SGLT2 inhibitors on IP, which could result in an important advance in the treatment of patients with stable CAD.

Aims: High precordial leads (HPL) on the resting electrocardiogram (ECG) are widely used to improve diagnostic detection of type 1 Brugada ECG pattern (Br1ECGp). A parasympathetic activation marks the initial recovery phase of treadmill stress testing (TET), and this can be useful for detecting the typical ECG pattern. Our study aimed to evaluate the role of a new HPL-treadmill exercise testing (TET) protocol in detecting Br1ECGp fluctuation compared to resting HPL-ECG., Methods and Results: 74 out of 163 patients of a Brugada syndrome (BrS) Brazilian cohort (GenBra Registry) underwent exercise testing with HPL-TET protocol. Precordial leads were displayed in strategic positions in the right and left parasternal spaces. The step-by-step analysis included ECG classification (as presence or absence of Br1ECGp) in standard vs. HPL leads placement in the following sequences: resting phase, maximal exercise, and the passive recovery phase (including 'quick lay down'). For heart rate recovery (HRR) measurements and comparisons, a Student's t-test was applied. McNemar tests compared the detection of Br1ECGp. The significance level was defined as P < 0.05. Fifty-seven patients (57/74; 77%) were male, the mean age was 49.0 ± 14, 78.4% had spontaneous BrS, and the mean Shanghai score was 4.5. The HPL-TET protocol increased Br1ECGp detection by 32.4% against resting HPL-ECG (52.7% vs. 20.3%, P = 0.001) alone., Conclusion: Stress testing using HPL with the passive recovery phase in the supine position offers an opportunity to unmask the type 1 Br1ECGp, which could increase the diagnostic yield in this population., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: To estimate the prevalence of exercise testing alterations in middle-aged women without symptoms of heart disease and to verify the associations of functional capacity and heart rate behavior during and after exercise with cardiovascular risk factors., Methods: A cross-sectional study was conducted with 509 asymptomatic women aged between 46 and 65 years who underwent clinical evaluations and exercise testing (Bruce protocol). The heart rate behavior was evaluated by the maximal predicted heart rate achieved, chronotropic index and recovery heart rate., Results: The mean age was 56.4±4.8 years, and 13.4% of the patients had a Framingham risk score above 10%. In the exercise treadmill testing, 58.0% presented one or more of the following alterations (listed in order of ascending prevalence): symptoms (angina, dyspnea, and dizziness), ST-segment depression, arrhythmia, reduction in recovery heart rate of ≤12 bpm at 1 minute, altered maximal predicted heart rate achieved, abnormal blood pressure, functional capacity deficiency, and altered chronotropic index. In the multivariate analysis, the following associations (odds ratio) were observed for these alterations: chronotropic index was associated with obesity (2.08) and smoking (4.47); maximal predicted heart rate achieved was associated with smoking (6.45); reduction in the recovery heart rate at 1 minute was associated with age (1.09) and obesity (2.78); functional capacity was associated with age (0.92), an overweight status (2.29) and obesity (6.51)., Conclusions: More than half of middle-aged women without cardiovascular symptoms present alterations in one or more exercise testing parameters. Alterations in the functional capacity or heart rate behavior, as verified by exercise testing, are associated with age, smoking, an overweight status and obesity.

Background: The need to improve the exercise testing accuracy, pushed the development of scores, whose applicability was already broadly recognized., Objective: Prognostic evaluation of stable coronary disease through a new simplified score., Methods: A new score was applied in 372 multivessel coronary patients with preserved ventricular function, 71.8% male, age: 59.5 (± 9.07) years old, randomized to medical treatment, surgery (CABG) or angioplasty (PTCA), with 5 years of follow-up. Cardiovascular death was considered the primary endpoint. Non-fatal myocardial infarction, death and re-intervention were considered for a combined secondary endpoint. The score was based on an equation previously validated, resulting from a sum of one point for: male gender, infarction history, angina, diabetes, insulin use and one point for each decade of life after 40 years old. Positive exercise testing summed one additional point., Results: Thirty six deaths was observed (10 in group PTCA, 15 in CABG and 11 in the clinical group), p = 0.61. We observed 93 combined events: 37 in PTCA group, 23 in CABG and 33 in the clinical group (p = 0.058). 247 patients presented clinical score ≥ 5 points and 216 ≥ 6 points. The cutoff point ≥ 5 or ≥ 6 points identified higher risk, p = 0.015 and p = 0.012, respectively. The survival curve showed a different death incidence after the randomization when score reached 06 points or more (p = 0.07), and a distinct incidence of combined events between the patients with score < 6 and ≥ 6 points (p = 0.02)., Conclusion: The new score was consistent for multiarterial stable coronary disease risk stratification.

Background: Restenosis after primary percutaneous coronary intervention (PPCI) remains an important clinical problem, even with stent implantation. The ability of noninvasive testing to diagnose restenosis has had only inconsistent demonstration., Objective: Our objective was to evaluate the ability of exercise treadmill testing (ETT) and myocardial perfusion imaging (MPI) to diagnose restenosis in patients treated by PPCI within 12 hours of ST-elevation myocardial infarction (STEMI)., Methods: From August 2003 to January 2006, 64 patients (mean age of 56.2±10.2 years, 53 males) were enrolled after PPCI. Only patients with left ventricular ejection fraction (LVEF) > 40%, as assessed by resting transthoracic echocardiography (TTE), were included. ETT with 12-lead ECG monitoring and right precordial leads, as also MPI were performed at 6 weeks, 6 months, and one year after intervention. Coronary angiography was performed at six months., Results: Single-vessel disease was observed in 46.9% of the patients. The left anterior descending coronary artery was treated in 48.4% of the patients. Angiographic restenosis occurred in 28.8%. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of ETT in detecting restenosis were not significant. Right precordial leads did not add information. MPI sensitivity, specificity, PPV, NPV, and accuracy correlated with restenosis only in the 6-month follow-up, both when considering summed difference score >2 (p=0.006) and >4 (p=0.014)., Conclusion: ETT did not discriminate restenosis in this population. MPI performed at 6 months correlated with restenosis and proved useful during follow-up.

The aim of this study was to test the hypothesis of differences in performance including differences in ST-T wave changes between healthy men and women submitted to an exercise stress test. Two hundred (45.4%) men and 241 (54.6%) women (mean age: 38.7 +/- 11.0 years) were submitted to an exercise stress test. Physiologic and electrocardiographic variables were compared by the Student t-test and the chi-square test. To test the hypothesis of differences in ST-segment changes, data were ranked with functional models based on weighted least squares. To evaluate the influence of gender and age on the diagnosis of ST-segment abnormality, a logistic model was adjusted; P < 0.05 was considered to be significant. Rate-pressure product, duration of exercise and estimated functional capacity were higher in men (P < 0.05). Sixteen (6.7%) women and 9 (4.5%) men demonstrated ST-segment upslope >or=0.15 mV or downslope >or=0.10 mV; the difference was not statistically significant. Age increase of one year added 4% to the chance of upsloping of segment ST >or=0.15 mV or downsloping of segment ST >or=0.1 mV (P = 0.03; risk ratio = 1.040, 95% confidence interval (CI) = 1.002-1.080). Heart rate recovery was higher in women (P < 0.05). The chance of women showing an increase of systolic blood pressure

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.

Objective: To assess the myocardial ischemic load to previous and after myocardial revascularization., Methods: Ninety-six randomized patients, carriers of multivessel coronary artery disease, stable angina, preserved left ventricular function, and exercise-induced myocardial ischemia treated with revascularization (SMR) or coronary angioplasty (TCA). Myocardial scintigraphy with 99mTc-Sestamibi was performed prior to and 6 months after myocardial revascularization., Results: The SMR determined a significant greater index of complete revascularization (p=0.001), an increase in the number of maximum ergometric tests (p=0.001) and reduction in the number of positive ergometric tests with exercise angina (p=0.018). Both procedures provided an important improvement in the functional class of angina (p=0.001), an increase in the average value of double peak product (p=0.009), and the time of exercise tolerance (p<0.001), besides the reduction in the average value of the summed of exercise score (p<0.001) and the difference of the summed of scores (p<0.001) in both groups., Conclusion: TCA and SMR did not differ significantly concerning the reduction of myocardial ischemic load 6 months after the procedure. The myocardial revascularization was more complete with the SMR than the TCA, but it did not represent a significant factor for the reduction myocardial ischemic load.

The effects of 12 months of therapy were evaluated in 47 mildly symptomatic patients with moderate to severe mitral valve regurgitation; 26 patients received enalapril and 21 received a placebo. Enalapril was associated with a significant reduction in left ventricular diameter and mitral regurgitation volume, with no evidence of change in systolic function indexes. However, enalapril did not hinder progressive aerobic impairment to effort.

Background: Myocardial perfusion imaging with dipyridamole is an alternative with which to evaluate patients who are unable to exercise. Many patients who undergo dipyridamole testing are limited in their ability, but are not completely unable, to exercise. There are benefits from adding low workload exercise to dipyridamole testing, including a reduction of thallium 201 concentration in the liver, leading to a higher heart-to-liver activity ratio and better image quality. This prospective study was designed to evaluate a protocol of exercise supplementation during dipyridamole technetium 99m sestamibi imaging and to verify whether a higher heart-to-liver activity ratio could be obtained. We also evaluated the potential of this combined protocol to prevent hypotension and induce ischemic changes on the electrocardiogram (ECG)., Methods and Results: Ninety consecutive patients who were not completely disabled for exercise underwent dipyridamole Tc-99m sestamibi cardiac single photon emission computed tomography with a protocol of exercise supplementation (DipEx). The heart-to-liver activity ratio, hemodynamics, and electrocardiographic changes were studied. The findings were compared with those of a control group (Dip) composed of 99 patients who underwent dipyridamole infusion alone. Patients with left bundle branch block, pacemaker, and atrial fibrillation were excluded. The DipEx patients tolerated the protocol, exercising 4.2 +/- 1.3 minutes on the treadmill (Bruce protocol). Compared with Dip, patients in the DipEx group had a higher heart-to-liver activity ratio (1.3 +/- 0.4 vs 1.6 +/- 0.5, respectively; P =.00001), had no incidence of hypotension (6% vs 0%, respectively; P =.03), and had a higher sensitivity of the ECG to detect ischemia (6% vs 34%, respectively; P =.003). The increase in sensitivity seen in the DipEx group was accompanied by a significant decrease in specificity compared with the Dip group (67% vs 100%, P =.000001)., Conclusions: Our data show that the addition of limited exercise to dipyridamole results in benefits during Tc-99m sestamibi imaging, increasing heart-to-liver activity ratio, preventing vasodilator-induced hypotension, and improving ECG sensitivity for the detection of ischemia. Furthermore, this protocol also provides an estimation of the patient's physical capacity and could be used as an alternative for patients undergoing dipyridamole infusion who are not completely unable to exercise.

Objective: To determine the predictive values of noninvasive tests for the detection of allograft vascular disease., Methods: We studied 39 patients with mean ages of 48+/-13 years and a follow-up period of 86+/-13 months. The diagnosis of allograft vascular disease was made by cine-coronary arteriography, and it was considered as positive if lesions existed that caused > or =50% obstruction of the lumen. Patients underwent 24h Holter monitoring, thallium scintigraphy, a treadmill stress test, and dobutamine stress echocardiography. Sensitivity, specificity, and positive and negative predictive values were determined in percentages for each method, as compared with the cine-coronary arteriography results., Results: Allograft vascular disease was found in 15 (38%) patients. The Holter test showed 15.4% sensitivity, 95.5% specificity. For the treadmill stress test, sensitivity was 10%, specificity was 100%. When thallium scintigraphy was used, sensitivity was 40%, specificity 95.8%. On echocardiography with dobutamine, we found a 63.6% sensitivity, 91.3% specificity. When the dobutamine echocardiogram was associated with scintigraphy, sensitivity was 71.4%, specificity was 87%., Conclusion: In this group of patients, the combination of two noninvasive methods (dobutamine echocardiography and thallium scintigraphy) may be a good alternative for the detection of allograft vascular disease in asymptomatic patients with normal ventricular function.

Objective: To compare single-photon-emission computed tomography (SPECT) imaging scans using 201Tl and 99mTc-MIBI in detection of viable myocardium, in regions compromised by infarction., Methods: Thirty-two (59.3 +/- 9.8 years old and 87% male) myocardial infarction patients were studied. All had Q waves on the ECG and left ventricle ejection fraction of < 50%. They underwent coronary and left ventricle angiographies and SPECT before (including 201Tl reinjection) and after coronary artery bypass surgery (CABG). Improvement in perfusion observed after surgery was considered the gold standard for myocardial viability., Results: Among 102 studied regions of the heart, there were 40 (39.2%) areas of transient perfusion defects in the conventional protocol with 201Tl and 52 (51.0%) after reinjection. Therefore, 12/62 (19.4%) more viable regions were identified by reinjection. Using 99mTc-MIBI, only 14 (13.7%) regions with transient defects were identified, all of which were seen also in 201Tl protocols. After surgery, 49 of a total of 93 regions analyzed (52.7%) were viable. Sensitivity, specificity, accuracy, positive and negative prediction values were, respectively, 201Tl SPECT scans--65.3%, 90.9%, 77.4%, 88.9% and 70.2%, reinjection protocol with 201Tl scans--81.5%, 81.8%, 81.7%, 83.3% and 80.0%, 99mTc-MIBI SPECT scans--20.4%, 90.9%, 53.8%, 71.4% and 50.6%. Logistic regression demonstrated that the reinjection protocol with 201Tl was the best predictor of viability (P < 0.001)., Conclusion: Our data suggest the election of 201Tl for viability studies, especially when using the reinjection protocol.

Unlabelled: The aim of the study was to register the prevalence of late potentials (LP) in patients with chronic Chagas' heart disease (CCD) and the relationship with sustained ventricular tachycardia (SVT). 192 patients (96 males), mean age 42.9 years, with CCD were studied through a Signal Averaged ECG using time domain analysis. According to presence or absence of bundle branch block (BBB) and SVT, four groups of patients were created: Group I (n = 72): without SVT (VT-) and without BBB (BBB-): Group II (n = 27): with SVT (VT+) and BBB-; Group III (n = 63): VT- and with BBB (BBB+); and Group IV (N = 30): VT+ and BBB+. The LP was admitted, with 40 Hz filter, in the groups without BBB using standard criteria of the method. In the group with BBB, the root-mean-square amplitude of the last 40 ms (RMS) < = 14 microV was considered as an indicator of LP., Results: In groups I and II, LP was present in 21 (78%) of the patients with SVT and in 22 (31%) of the patients with SVT (p < 0.001), with Sensitivity (S) 78%; Specificity (SP) 70% and Accuracy (Ac) 72%. LP was present in 30 (48%) of the patients without and 20 (67%) of the patients with SVT, in groups III and IV. p = 0.066, with S = 66%; SP = 52%; and Ac = 57%. In the follow-up, there were 4 deaths unrelated to arrhythmic events, all of them did not have LP. Eight (29.6%) of the patients from group II and 4 (13%) from group IV presented recurrence of SVT and 91.6% of these patients had LP., Conclusions: LP occurred in 77.7% of patients with SVT and without BBB. In the groups with BBB, there was association of LP with SVT in 66.6% of the cases. The recurrence of SVT was patient in 21% of the cases from which 91.6% had LP.

Purpose: To verify if a third series of images acquired by reinjection thallium-201, 24h after conventional myocardial perfusion with the radioisotope, improves the identification of myocardial viability segments., Methods: We studied 30 patients, mean age 57.7 +/- 9.4 years, with old myocardial infarction using thallium (Tl)-201 SPECT (single-photon-emission computed tomography), and we obtained 3 series of images (stress, redistribution after 4h and reinjection after 24h. Cardiac images were divided in 5 segments (apical, lateral, anterior, septal and inferior) and each one received a value by a score system according to the Tl-201 myocardial uptake (0 = normal uptake; 1 = mild hypoperfusion; 2 = moderate hypoperfusion; 3 = severe hypoperfusion or no myocardial uptake). We considered viable myocardium when the uptake of Tl-201 in the segment related to the myocardial infarction increased at least 1 point in two different axis of Tl-201 SPECT., Results: Seven (23.3%) patients demonstrated increase of Tl-201 uptake only at reinjection images, showing a higher efficacy of the method. Nine (30%) patients showed persistent hypoperfusion at all series of images suggesting only fibrosis in the area related to the infarction. Fourteen (46.7%) patients showed increase of Tl-201 concentration at redistribution images; among these patients, six showed improvement of myocardial uptake at reinjection. This condition were interpreted as regional chronic ischemic process: hibernating myocardium., Conclusion: Tl-201 hypoperfusion at redistribution images without significant changes in relation to the stress images do not represent fibrosis at all. The reinjection technic was better than conventional redistribution in the detection of viable myocardium. This data allows a better therapeutic orientation.

Purpose: To describe groups of patients who have obstructive and non-obstructive coronary artery disease, through computadorized exercise stress test., Methods: The test was done in 121 patients, all male, divided into 3 groups: GN group, 50 patients with normal electrocardiographic response to exercise; GLO group, 40 patients with obstructive coronary artery disease and GNO group, 31 patients with normal coronary arteries, showing one or more of the following entities: intramural coronary traject, coronary tortuosity, slow flow, mitral valve prolapse or left ventricular hypertrophy. GLO and GNO groups presented with abnormal response of the ST segment during exercise. The quantitative variables registered by computer were particularly analyzed as follows: STL (point Y depression), slope, index and ST segment integral. The magnitude of ST vector was visually measured and quantified. The statistic study was made through ANOVA and multiples comparison by the Scheffe's method, Fisher's test, quisquare and sensibility, specificity and accuracy calculation., Results: There was a significant statistic difference among the 3 groups relative to slope and index (p < 0.05). The integral variable of ST segment did not allow us to differentiate the GLO and GNO groups. In the association study between the ST vector magnitude and abnormal T loop, there was an increase in sensibility of 15% in the exercise stress test., Conclusion: The ST segment slope below zero values, define patients having obstructive disease, and the opposite, non-obstructive disease. Values of ST segment index lower than -2 are linked to obstructive disease and higher than -2 linked to non-obstructive. Values of ST segment lower than -7 microV. s separate individuals with normal exercise stress test from those with ischemic type response. The magnitude of ST vector equal to or lower than 0.20mV define normal vectorcardiographic response to the exercise.

Purpose: To analyze adverse reactions (AR), hemodynamic and electrocardiographic changes and thallium scintigraphy (TS) results, during pharmacological stress with dipyridamole (SD), correlating these data to the presence and extension of coronary artery disease (CAD)., Methods: We studied 126 patients, 66 had no evidence of cardiovascular disease (G1) and 60 had critical occlusive CAD > or = 70% stenosis (G2). Most of them were male, mean age 56.5 +/- 10.9 years old. All patients were submitted to TS after receiving 0.56 mg/kg of dipyridamole intravenously (0.14 mg/min during 4 min) followed by 111MBq of thallium-chloride-201. Conventional ECG was recorded before and after SD; heart rate (HR) and arterial pressure (AP) were monitored during dipyridamole infusion. All signals and/or symptoms were observed., Results: Cine-coronarography showed 22 patients (37%) with one vessel disease (VD) (G2a), 26 (46%) with two VD (G2b) and 12 (20%) with three VD (G2c). Of the 126 patients 63% did not present symptoms. Flushing (25%) and sick-headache (12%) were most frequent AR. Typical angina was reported by one G1 patient (1.5%) and six G2 patients (10%) (p < 0.05). HR increased 18.09 +/- 12.27% and 12.40 +/- 4.90%, systolic blood pressure varied -5.2 +/- 7.5% and -4.3 +/- 6.5% in G1 and G2, respectively. These parameters are not correlated to CAD presence and extension. ST depression and ectopic beats occurred in 5% and 11% of G1 patients, in 15% and 30% of G2 patients, respectively (p < 0.05). Typical angina was more common in G2a and G2b; ST changes in G2b and G2c; and arrhythmia in G2c (not significant). Sensitivity of TS associated to SD was 84%, comparable to stress exercise thallium test., Conclusion: TS associated to SD, a noninvasive, safe with low morbidity and few collateral effects method is an option to patients with limitations to physical exercise tests.