Exercise-induced Myocardial Ischemia Research Articles

Relation between high-sensitivity troponin i serum levels and myocardial ischemia in patients with suspected chronic coronary syndrome: the RESET-MI study

Abstract Background Previous studies showed that exercise may increase cardiac troponin serum levels; however, whether exercise-induced myocardial ischemia influences the exercise-induced increase of troponin levels remains debatable. Methods We prospectively enrolled consecutive patients undergoing an elective stress myocardial perfusion scintigraphy (MPS) because of a clinical suspicion of obstructive coronary artery disease (CAD). Patients were divided into 3 groups according to the evidence and degree of stress-induced myocardial ischemia at MPS: 1) Group 1, no ischemia (≤4% of myocardium); 2) Group 2, mild ischemia (5-10%); 3) Group 3, moderate-to-severe myocardial ischemia (≥10%). High-sensitivity cardiac troponin I (cTnI) was measured immediately before (T0) and 1 hour (T1) and 4 hours (T2) after the stress test. A successive evaluation of patients was performed at 24 months. Results One-hundred consecutive patients (64 males; age 65.5±9.5 years) were enrolled in the study. An exercise stress test and a dipyridamole stress test were performed in 81 and 19 patients, respectively. Serum hs-cTnI concentrations significantly increased after stress test, compared to baseline, in the whole population, from (median, interquartile range) 3.9 (2.5-6.1) ng/L at T0, to 4.2 (2.8-7.3) ng/L at T1 (p<0.001) and 6.7 (3.8-14.1) ng/L at T2 (p<0.001 vs. both T0 and T1). The increase in hs-cTnI did not significantly differ between the 3 groups (p=0.35; Figure). The increase was significant after both exercise (+54.5%) and dipyridamole (+18.2%), although the increase was greater after exercise (p=0.002). Heart rate achieved during the test was the strongest determinant of cTnI increase after the stress test (p < 0.001). Conclusions In patients with suspected CAD, stress MPS induces an increase of cTnI that is independent of the induction and severity of myocardial ischemia and is mainly related to myocardial work, as indicated by heart rate achieved during the stress test.Figure

Men with non-obstructive coronary disease have higher risk of exercise-induced myocardial ischemia detected by cardiopulmonary exercise test

Abstract Background Non-obstructive coronary artery disease (NOCAD) had similar morbidity and mortality as patients with obstructive coronary artery disease but less understood. Limited studies analyzed the gender differences in inducible myocardial ischemia assessed by cardiopulmonary exercise test (CPET) in NOCAD. Methods A total of 289 NOCAD patients (mean age 60, 56% women) who had ischemic symptoms and ⫹ 50% coronaries stenoses confirmed by coronary angiography performed the symptom-limited CPET. We used the predicted % peak VO2, O2 pulse trajectory, and exercise ECG test to assess inducible myocardial ischemia. Results Compared with women, men with NOCAD had significantly lower predicted % peak VO2 (62% vs. 73%), higher proportions of flattening pattern (16% vs. 2%) and downward pattern of O2 pulse trajectory (2% vs. 0%) (P < 0.0001). Instead, women with NOCAD had higher prevalence of shallow pattern of O2 pulse trajectory (21% vs. 6%, P < 0.0001). Men with NOCAD had higher proportions of increased risk of exercise-induced myocardial ischemia (medium risk: 63% vs. 54%, high risk: 18% vs. 4%, P < 0.0001). After adjustment, men with NOCAD demonstrated significantly lower predicted % peak VO2 (β -27.4, 95% CI -30.74 – -24.07), higher risk for abnormal O2 pulse trajectories (OR 4.21, 95% CI 1.93 – 9.19) and myocardial ischemia risk detected by CPET (OR 3.14, 95% CI 1.78 – 5.54) (P < 0.0001). Conclusion Men with NOCAD had higher risk of exercise-induced myocardial ischemia detected by CPET that should be given rigorous management and follow-up to prevent cardiovascular events.

Serum N-6 Polyunsaturated Fatty Acids And Exercise-Induced Myocardial Ischemia

Serum N-6 Polyunsaturated Fatty Acids And Exercise-Induced Myocardial Ischemia

Exercise-induced myocardial ischemia presenting as exercise intolerance after carbon monoxide intoxication and smoke inhalation Injury: case report

BackgroundCarbon monoxide intoxication and smoke inhalation injury can lead to severe disorders, and the current literature has elaborated on the importance of major cardiopulmonary impairment. Exercise intolerance has seldom been discussed, particular in patient with low cardiovascular risk.Case presentationTwo young male fire survivors who presented with exercise intolerance after CO intoxication and smoke inhalation injury. Both received bronchodilator and glucocorticoid therapy, high-flow oxygen therapy, and hyperbaric oxygen therapy for airway edema and CO intoxication during acute care. Serum carboxyhemoglobin levels improved after treatment (8.2–3.9% in Case A and 14.8–0.8% in Case B). However, subjective exercise intolerance was noted after discharge. Cardiopulmonary exercise testing revealed exercise-induced myocardial ischemia during peak exercise (significant ST-segment depression on exercise electrocardiogram). They were instructed to exercise with precaution by setting the intensity threshold according to the ischemic threshold. Their symptoms improved, and no cardiopulmonary events were reported in the 6-month follow-up.ConclusionThe present case report raised the attention that exercise intolerance after carbon monoxide intoxication and smoke inhalation injury in low cardiovascular risk population may be underestimated. Cardiopulmonary exercise testing help physician to discover exercise-induced myocardial ischemia and set up the cardiac rehabilitation program accordingly.

253 EXCERCISE-INDUCED PULMONARY HYPERTENSION AND CORONARY ARTERY ANOMALY: AN UNUSUAL ASSOCIATION

Abstract A healthy 55-year-old competitive sportsman, with familial history of early sudden cardiac death, came to our attention following the finding of asymptomatic exercise-induced myocardial ischemia (ST depression in V3- V6). Computed tomography (CT) coronary angiogram excluded atherosclerotic disease but showed a dominant right coronary artery (RCA) originating from left Valsalva sinus and with an interarterial course between the ascending aorta and the pulmonary artery. Both the trunk of the pulmonary artery and the right ventricle were reported as mildly dilated Transthoracic echocardiography showed a normal left ventricle (LV), while confirmed right ventricle (RV) dilatation, moderate tricuspid regurgitation (TR) and interatrial septal aneurysm. Stress echocardiography excluded inducible ischemia, but highlighted exercise-induced pulmonary hypertension (PH) (PAPs 25 → 70 mmHg), while a transesophageal echo confirmed a left-to-right shunt due to a 8-mm Patent Foramen Ovale (PFO). Rheumatological, thromboembolic and parenchymal lung diseases were excluded as possible causes of exercise-induced PH; a rest right heart catheterization (RHC) showed a Qp/Qs ratio at the upper limits of normal range without PH. Nuclear stress testing identified trivial asymptomatic septal ischemia. The patients started medium dose of beta-blockers and early follow-up was planned. This clinical case raises some questions: why is RV dilated? What role does PFO play? What is the cause of the inducible ischemia? What is the pathogenesis of exercise-induced PH? Pulmonary Arterial Hypertension, in early stages, often manifests only under exertion, but it is usually characterized by exercise dyspnea and low oxygen saturation. Moreover, intracardiac shunts may be involved in developing PH. In this specific case, pulmonary trunk may be expanded by pressure overload, causing the compression of aberrant RCA and consequent ischemic abnormalities. RV dilatation might be explained by exercise-induced PH itself, but it was not severe and has to be demonstrated by exercise right heart catheterization. The main questions are: which is the primary etiology of right chamber enlargement and myocardial ischemia? Which is the most appropriate therapeutic approach (i.e. conservative vs interventional)?

Diagnostic accuracy of instantaneous wave-free ratio at rest and during dobutamine provocation to assess myocardial bridging relevance

Abstract Background Diastolic fractional flow reserve (d-FFR) during dobutamine provocation (DOB) was found to be a more reliable physiological index for the functional assessment of myocardial bridging (MB). However, d-FFR calculation is complicated and time-consuming, and therefore several authors have suggested the use of instantaneous wave-free ratio (iFR) to overcome these issues. Purpose The aim of our study was to assess diagnostic performance of d-FFR and iFR at rest and during DOB with exercise-induced myocardial ischemia as reference. Methods Twenty-four symptomatic patients (17 males, mean age 58±8 years) with MB and systolic compression ≥50% diameter stenosis on the left anterior descending (LAD) artery were included. Exercise stress-echocardiography test (SE), and both d-FFR and iFR in the distal segment of LAD at rest and peak DOB (30–50μg/kg/min), were performed in all patients. Optimal cut-off values and diagnostic performance of resting and hyperemic d-FFR and iFR were assessed using SE. Results Exercise-SE was positive for myocardial ischemia in 7/24 patients (29%). The area-under-the-receiver-operating-characteristic curve (ROC-AUC) for exercise-induced myocardial ischemia was 0.64 (95% CI: 0.400–0.885) for resting d-FFR, 0.62 (95% CI: 0.378–0.866) for resting iFR, 1.000 (95% CI: 0.999–1.000) for d-FFR at peak DOB, and 0.96 (95% CI: 0.895–1.000) for iFR at peak DOB. No significant difference in ROC-AUC was observed between d-FFR and iFR at peak DOB (p=0.243). The best cut-off value for both d-FFR and iFR at peak DOB was <0.76 with similar sensitivity and negative predictive values (100 vs. 100% for both), but lower specificity and positive predictive value for iFR in identifying MB associated with exercise-induced ischemia (94% vs. 82%; 88% vs. 70%, respectively). Compared with exercise-induced myocardial ischemia, the diagnostic accuracy of d-FFR and iFR at peak DOB was 96% (kappa=0.903, p<0.001) and 88% (kappa=0.731, p<0.001), respectively. Conclusions iFR during DOB provocation showed similar diagnostic accuracy as d-FFR to identify the functionally significant MB when compared with exercise-induced myocardial ischemia. Funding Acknowledgement Type of funding sources: None.

Diastolic stress echocardiography in patients with normal resting diastolic function: prognostic utility in presence and absence of myocardial ischemia

Abstract Background Abnormal diastolic response to exercise is reportedly associated with worse cardiovascular events. However, this has not been well studied in patients with normal diastolic function at rest. Purpose We sought to study diastolic response to exercise in patients referred for exercise stress echocardiography (ExE) and to explore its association with adverse outcomes in the presence and absence of exercise-induced myocardial ischemia. Methods In a retrospective study, patients referred for ExE to assess myocardial ischemia between April 2017 and December 2018 were enrolled. Patients were included if they had guideline-defined normal diastolic function at rest and availability of a full set of post exercise diastolic variables (post exercise tissue Doppler derived septal mitral annular early diastolic velocity (e'), ratio of pulsed Doppler derived mitral forward flow early diastolic velocity (E) over e' (E/e') and continuous wave Doppler derived maximum tricuspid regurgitation velocity (TRV)). The patients were followed for a median of 3.4 years for the occurrence of composite death, acute coronary syndrome, cardiac hospitalization, and need of follow-up ischemia testing. Abnormal exercise diastolic variables were defined as e' <7 cm/s, E/e' >15, and TRV >2.8 m/s. Results We studied 492 patients [age: 55.7±12.9 year, 268 (54%) women, EF: 61±5.8%]. Mean achieved metabolic equivalents of tasks (METs) was 9.7±3.1, and a total of 49 (10%) patients had evidence of exercise-induced ischemia. At rest, mean left atrial volume index was 25.4±12 ml, e' was 8±2 cm/s, E/e' was 9.5±2.4, and TRV was 2.1±0.44 m/s. Post exercise e' was 10±3 cm/s [<7cm/s in 63 (13%)], E/e' was 11.1±3.9 [>15 in 95 (19%)], and TRV was 2.37±0.68 m/s [>2.8 m/s in 152 (31%)]. Ischemic ExE was found to be strongly associated with the outcome (HR: 4.46, 95% CI: 2.8 to 7.1, p<0.001). In addition, all diastolic variables predicted the outcome in isolation if they were abnormal (e': 2.28, 95% CI: 1.4 to 3.7, p=0.001, E/e': 1.81; 95% CI: 1.15 to 2.84, p=0.01; TRV: 1.58, 95% CI: 1.17 to 2.13, p=0.003). When combined, however, association with the outcome was seen only when 2 or 3 of these variables were abnormal simultaneously (Figure 1A). When patients were stratified by ischemia and abnormal diastolic variables (figure 1B), patients with 2 or 3 abnormal variables were more likely to experience the outcome compared to patients with 0 or 1 abnormal variables in both absence of ischemia (p<0.001) and presence of ischemia (p=0.016). The stratified groups were different in their clinical and exercise profiles, with worse profiles in patients with both ischemia and 2 or 3 abnormal variables, and best profiles in patients with no ischemia and 0 or 1 abnormal variables. Conclusions In patients referred for ExE to assess ischemia with normal baseline diastolic function, exercise can unmask abnormal diastolic properties and stratify patients' risk regardless of the overt myocardial ischemia. Funding Acknowledgement Type of funding sources: None.

Challenges in Diagnosis and Functional Assessment of Coronary Artery Disease in Patients With Severe Aortic Stenosis.

More than half of patients with severe aortic stenosis (AS) over 70 years old have coronary artery disease (CAD). Exertional angina is often present in AS-patients, even in the absence of significant CAD, as a result of oxygen supply/demand mismatch and exercise-induced myocardial ischemia. Moreover, persistent myocardial ischemia leads to extensive myocardial fibrosis and subsequent coronary microvascular dysfunction (CMD) which is defined as reduced coronary vasodilatory capacity below ischemic threshold. Therefore, angina, as well as noninvasive stress tests, have a low specificity and positive predictive value (PPV) for the assessment of epicardial coronary stenosis severity in AS-patients. Moreover, in symptomatic patients with severe AS exercise testing is even contraindicated. Given the limitations of noninvasive stress tests, coronary angiography remains the standard examination for determining the presence and severity of CAD in AS-patients, although angiography alone has poor accuracy in the evaluation of its functional severity. To overcome this limitation, the well-established invasive indices for the assessment of coronary stenosis severity, such as fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR), are now in focus, especially in the contemporary era with the rapid increment of transcatheter aortic valve replacement (TAVR) for the treatment of AS-patients. TAVR induces an immediate decrease in hyperemic microcirculatory resistance and a concomitant increase in hyperemic flow velocity, whereas resting coronary hemodynamics remain unaltered. These findings suggest that FFR may underestimate coronary stenosis severity in AS-patients, whereas iFR as the non-hyperemic index is independent of the AS severity. However, because resting coronary hemodynamics do not improve immediately after TAVR, the coronary vasodilatory capacity in AS-patients treated by TAVR remain impaired, and thus the iFR may overestimate coronary stenosis severity in these patients. The optimal method for evaluating myocardial ischemia in patients with AS and co-existing CAD has not yet been fully established, and this important issue is under further investigation. This review is focused on challenges, limitations, and future perspectives in the functional assessment of coronary stenosis severity in these patients, bearing in mind the complexity of coronary physiology in the presence of this valvular heart disease.

Does exercise stress testing carry an incremental prognostic value beyond resting office blood pressure?

Does exercise stress testing carry an incremental prognostic value beyond resting office blood pressure?

Incremental value of high-frequency QRS analysis for diagnosis and prognosis in suspected exercise-induced myocardial ischaemia.

Exercise stress testing is used to detect myocardial ischaemia, but is limited by low sensitivity and specificity. The authors investigated the value of the analysis of high-frequency QRS components as a marker of abnormal depolarization in addition to standard ST-deviations as a marker of abnormal repolarization to improve the diagnostic accuracy. Consecutive patients undergoing bicycle exercise stress nuclear myocardial perfusion imaging were prospectively enrolled. Presence of myocardial ischaemia, the primary diagnostic endpoint, was adjudicated using MPI and coronary angiography. Automated high-frequency QRS analysis was performed in a blinded fashion. The prognostic endpoint was major adverse cardiac events (MACEs) during two years of follow-up. Exercise-induced ischaemia was detected in 147/662 patients (22%). The sensitivity of high-frequency QRS was similar to ST-deviations (46% vs. 43%, p=0.59), while the specificity was lower (75% vs. 87%, p<0.001). The combined use of high-frequency QRS and ST-deviations classified 59% of patients as 'rule-out' (both negative), 9% as 'rule-in' (both positive) and 32% in an intermediate zone (one test positive). The sensitivity for 'rule-out' and the specificity for 'rule-in' improved to 63% and 97% compared with ST-deviation analysis alone (both p<0.001). MACE-free survival was 90%, 80% and 42% in patients in the 'rule-out', intermediate and 'rule-in' groups (p<0.001). After adjustment for age, gender, ST-deviations and clinical post-test probability of ischaemia, high-frequency QRS remained an independent predictor for the occurrence of MACEs. The use of high-frequency QRS analysis in addition to ST-deviation analysis improves the diagnostic accuracy during exercise stress testing and adds independent prognostic information.

Low or Even Zero CAC may not be Warranted as Safe in Thai Officers: A 10-year prospective

OBJECTIVES: CAC has been widely accepted as a strong independent event predictor in asymptomatic moderate risk in the western population. However, the role of coronary artery calcium (CAC) has not been established in the Thai population yet. Thus, we conducted a 10-year prospective study to verify the predictive role of CAC in asymptomatic Thai participants. &nbsp; MATERIAL AND METHODS: A total of 239 asymptomatic officers were voluntarily&nbsp;enrolled and consented to take part. We excluded participants aged &lt; 35 or &gt; 60 years, prior cardiovascular diseases (CVD), pregnant and those not willing to sign an informed consent of participation. The population underwent an exercise stress test (EST) to screen for occult coronary artery disease (CAD). Coronary angiography was performed if there is an evidence of&nbsp;exercise-induced myocardial ischemia within 7 METS. All the studied population underwent&nbsp;a 256-slide multidetector computed tomography (MDCT) scan to&nbsp;obtain a CAC scoring. CAC volume was measured by Agaston method which defines&nbsp;CAC as a&nbsp;mass of HU 130 or more. The studied population were divided into two groups,CAC = 0 and CAC &gt; 0. All of them received medication, education for lifestyle modification&nbsp;and were followed up annually for ten consecutive years (2006-2016).&nbsp;Primary end points&nbsp;were fatal or non-fatal acute coronary syndrome (ACS) and any types of stroke.&nbsp;Secondary&nbsp;end&nbsp;point&nbsp;was all causes of mortality. Student t test and Pearson’s Chi-square were used&nbsp;to&nbsp;compare the difference and the p value of &lt; 0.05 was considered statistically significant. RESULT: Most candidates were men (96.7%) and had a mean age of 52.4 ± 4.8 years. The common coronary risk factors were elevated low density lipoprotein cholesterol (LDL-C) &gt;130 mg/dl (66.9%), elevated triglyceride (TG) &gt; 150 mg/dl (53.1%), systolic blood pressure (SBP) &gt; 140 mmHg (39.7%), impaired fasting glucose &gt; 100 mg/dl (34.5%), cigarette smoking (32.2%) and low high-density lipoprotein cholesterol (HDL-C) &lt; 40 mg/dl, (12.6%). Ten cases (4.2%) had ischemic exercise test (EST) response and 50% of them had severe coronary stenosis requiring revascularization or aggressive medication. The other half also had documented causes of exercise-induced ischemia including coronary slow flow, vasospasm and myocardial bridging. Thus, all of these cases were excluded for outcome measurement, therefore we had total of 229 cases, half (51.5%) of them had no detectable calcified coronary plaque using the Agaston-130 method (CAC = 0). There was no statistical difference in age, gender, SBP, fasting blood sugar (FBS), total serum cholesterol (T. Chol), serum TG, HDL-C and cigarette smoking between candi- dates with absent or present CAC, except the mean LDL-C which was statistically significantly higher in the group with no CAC, 154.7 vs 143.7 mg/dl, p = 0.036. After ten years, there were 23 CVD events including 3 ACS cases, 9 strokes (all ischemic type) and 11 deaths (91% were non-CVD causes). There was no statistically significant difference between these events in the two groups, CAC = 0 (n = 121) vs CAC &gt; 0 (n = 108) regarding to; ACS 0.8% vs 1.9% (p = 0.603), stroke 5% vs 2.8% (p = 0.506), death 2.5% vs 7.4% (p = 0.121) and the combined outcome (ACS + stroke + death): 8.3% vs 12% (p = 0.384). The mean CAC in CVD victims was quite low, 32.76 (0 - 53.1) for three ACS cases and 23.75 (0 - 180.9) for nine strokes. CONCLUSION: While the small number and the prominent male gender of candidates were the major limitations and precluded extrapolation to others, this study was the first 10-year cohort that reported different results from western studies, low or even zero CAC might not be safe in asymptomatic Thai people. Thus, we should be skeptical to use CAC as a CVD risk predictor in our population. Whether or not Thai men had low prevalence of calcified coronary plaque or had a different pathophysiologic mechanisms, further study in a larger population is mandatory.

PO-219 Experimental study on exercise intervention to improve cardiac risk during exercise in men aged 40~49 years

Objective Through 12 weeks exercise interventions of different exercise volume (1200kal/w or 2000kcal/w) on 40-49 years old male subjects，trying to explore the effect of exercise intervention on the d risk indicators of ECG (ST、QTcd) during the exercise, to provide a scientific basis for the public health in the future .&#x0D; Methods The subjects were randomly divided into 3 groups. (1)control group (n=9); (2) low volume group (n=7); (3) high volume group (n=8). The exercise group exercise intervention lasted 12 weeks. The indices of HRV at rest and risk indices of ECG (ST、QTcd)during exercise.&#x0D; Results (1) Compared the underdraught of ST segment during exercise before and after the intervention, we found that exercise intervention did not produce significant change, and QTcd during the exercise in both high and low volume group after the intervention was significantly lower than before (P &lt;0.05). (2) Compared the difference of ECG indices during exercise before and after, we found that descender of QTcd in low volume was significantly higher than the control group (P&lt;0.05), while the descender of QTcd in high group was very significantly higher than the control group (P&lt;0.01). The difference of ST segment in different group did not have significantly change.&#x0D; Conclusions (1) 12 weeks exercise intervention (intensity of 65-80% VO2max, exercise volume of 2000kcal/w) has no effect under the pressure amplitude of the ST segment during the exercise. (2) 12 weeks exercise intervention (intensity of 65-80% VO2max, exercise volume of 2000kcal/w) produce QTcd during exercise significantly reduced, reducing the risk of exercise-induced myocardial ischemia.&#x0D;

Exercise-related resuscitated out-of-hospital cardiac arrest due to presumed myocardial ischemia: Result from coronary angiography and intravascular ultrasound

AimPossible causes of exercise-related out-of-hospital cardiac arrest (OHCA) in people with coronary artery disease (CAD) include atherosclerotic plaque rupture (PR) and intra-coronary thrombosis, exercise-induced myocardial ischaemia and other triggers. We investigated whether there are differences in the incidence of PR and/or intra-coronary thrombus and in clinical outcome between ‘exercise-related’ and ‘non-exercise-related’ OHCA. Methods219 consecutive resuscitated patients with CAD diagnosed by emergency coronary angiography (CAG) were enrolled. They were divided into the exercise group (≥6 METs; n = 35) and non-exercise group (<6 METs; n = 184), according to estimated METs immediately before OHCA using 2011 Compendium of Physical Activities. We investigated whether culprit lesions had PR and/or thrombus using CAG and intravascular ultrasound. The clinical outcome was 30-day survival with minimal neurologic impairment. ResultsAcute PR and/or thrombus occurred in fewer of the exercise group than the non-exercise group (11% vs. 90%; P < 0.001). The exercise group had a higher incidence of favorable neurological outcome (94% vs. 47%; P < 0.001) than the non-exercise group. Multivariable Cox proportional hazards models revealed that exercise immediately before OHCA was one of the predictors of a good neurological outcome (HR, 0.19; P = 0.025). ConclusionThe incidence of PR and/or thrombosis was lower in the group taking higher levels of exercise, than in the group taking less or no exercise. “Exercise-related” OHCA with CAD has better clinical outcomes than “non-exercise-related” with a greater proportion of witnessed arrests and early return of spontaneous circulation.

Associations of the serum long-chain omega-3 polyunsaturated fatty acids and hair mercury with exercise-induced myocardial ischemia in men: The kuopio ischaemic heart disease risk factor study

Rationale: Long-chain omega-3 polyunsaturated fatty acids (PUFA) from fish is associated with lower risk of coronary heart disease (CHD). Fish may also contain methylmercury, which is associated with higher CHD risk. However, mechanisms underlying these associations are not fully known. We investigated the association of serum long-chain omega-3 PUFA and hair mercury concentrations with the odds for myocardial ischemia during exercise, a predictor of future cardiac events.

Role of Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in cardioprotection of exercise preconditioning.

To investigate the role of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the cardioprotective mechanisms of exercise preconditioning (EP). Eighty male Sprague-Dawley (SD) rats were randomized into the Group control, Group EE, Group EP+EE, Group EP+EE+AG, and Group EE+AG. By using 3 days of intermittent treadmill exercise, this study established the EP animal model. Rats were subjected to run to exhaustion on the treadmill at 30 m/min with 0% grade as an exhaustive exercise (EE) protocol. The myocardial injury induced by exhaustive exercise was produced 24 h after EP. JAK2 inhibitor (AG490, 3 mg/kg) was injected before EP. Serum cardiac troponin I (cTnI) levels and hematoxylin basic fuchsine picric acid (HBFP) staining were used to observe the degree of myocardial ischemia. TUNEL, Bcl2, and cleaved caspase-3 levels were used to evaluate the change of myocardial apoptosis. Moreover, the phosphorylations of JAK2 and STAT3 were analyzed as possible mechanisms that might explain the EP-induced cardioprotection. EP significantly attenuated the exhaustive exercise-induced myocardial ischemia injury, associated with lower serum cTnI levels, decreased myocardial infarct area, reduced myocardial apoptosis, increased Bcl2 level, decreased cleaved caspase-3 level, and the increased phosphorylations of JAK2 and STAT3. Treatment with AG490 abolished the cardioprotective effects and the enhanced phosphorylations of JAK2 and STAT3 induced by EP. EP plays its cardioprotective role via activating the JAK2/STAT3 signaling pathway, reducing the apoptosis of myocardial cells and alleviating myocardial ischemia injury.

Value of the coronary artery disease consortium rule in patients with acute chest pain and negative troponins referred for exercise stress testing.

To assess the value of the pretest probability (PTP) of coronary artery disease (CAD) for predicting stress testing results and coronary events in patients with acute chest pain and negative troponins. A total of 3527 patients without a history of CAD referred to our chest pain unit with suspected acute coronary syndromes, nondiagnostic ECGs, and negative troponin levels underwent exercise stress testing. PTP was estimated with the CAD consortium prediction rule, and was categorized as low (<15%), low-intermediate (15-65%), intermediate-high (66-85%), and high (>85%). The endpoints were the presence of signs of inducible myocardial ischemia on stress testing and the occurrence of coronary events within 6 months. The probability of exercise-induced myocardial ischemia was 2.6, 12.6, 42.9, and 82.1% in patients with low, low-intermediate, intermediate-high, and high PTP, respectively (Ptrend<0.001). The cumulative rate of coronary events within 6 months was also significantly lower in patients with low PTP of CAD (0.8%) than in those with low-intermediate (6.9%), intermediate-high (32.5%), or high PTP (66.7%) (Ptrend<0.001). Per 10% increment in PTP of CAD, the adjusted odds ratios for inducible myocardial ischemia and coronary events within 6 months were, respectively, 1.71 (95% confidence interval: 1.61-1.85) and 1.87 (95% confidence interval: 1.74-2.01). PTP was associated strongly with the likelihood of exercise-induced myocardial ischemia and coronary events in patients with suspected acute coronary syndromes and negative troponins. The yield of stress testing in the subset of patients with low PTP was very low.

Myocardial Ischemia and Mobilization of Circulating Progenitor Cells.

BackgroundThe response of progenitor cells (PCs) to transient myocardial ischemia in patients with coronary artery disease remains unknown. We aimed to investigate the PC response to exercise‐induced myocardial ischemia (ExMI) and compare it to flow mismatch during pharmacological stress testing.Methods and ResultsA total of 356 patients with stable coronary artery disease underwent 99mTc‐sestamibi myocardial perfusion imaging during exercise (69%) or pharmacological stress (31%). CD34+ and CD34+/chemokine (C‐X‐C motif) receptor 4 PCs were enumerated by flow cytometry. Change in PC count was compared between patients with and without myocardial ischemia using linear regression models. Vascular endothelial growth factor and stromal‐derived factor‐1α were quantified. Mean age was 63±9 years; 76% were men. The incidence of ExMI was 31% and 41% during exercise and pharmacological stress testing, respectively. Patients with ExMI had a significant decrease in CD34+/chemokine (C‐X‐C motif) receptor 4 (−18%, P=0.01) after stress that was inversely correlated with the magnitude of ischemia (r=−0.19, P=0.003). In contrast, patients without ExMI had an increase in CD34+/chemokine (C‐X‐C motif) receptor 4 (14.7%, P=0.02), and those undergoing pharmacological stress had no change. Plasma vascular endothelial growth factor levels increased (15%, P<0.001) in all patients undergoing exercise stress testing regardless of ischemia. However, the change in stromal‐derived factor‐1α level correlated inversely with the change in PC counts in those with ExMI (P=0.03), suggesting a greater decrease in PCs in those with a greater change in stromal‐derived factor‐1α level with exercise.ConclusionsExMI is associated with a significant decrease in circulating levels of CD34+/chemokine (C‐X‐C motif) receptor 4 PCs, likely attributable, at least in part, to stromal‐derived factor‐1α–mediated homing of PCs to the ischemic myocardium. The physiologic consequences of this uptake of PCs and their therapeutic implications need further investigation.

Combining high-sensitivity cardiac troponin and B-type natriuretic peptide in the detection of inducible myocardial ischemia

BackgroundSingle biomarker approaches provide only moderate accuracy in the non-invasive detection of exercise-induced myocardial ischemia. We therefore assessed the combination of the two most promising single biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) and B-type natriuretic peptide (BNP). MethodsConsecutive patients with suspected myocardial ischemia referred to stress myocardial perfusion single-photon emission tomography imaging (MPI) were enrolled. Clinical judgment (CJ) of the treating cardiologist regarding myocardial ischemia, quantified using a visual analogue scale, and blood concentrations of hs-cTnI and BNP were determined before and after stress. The presence of myocardial ischemia was adjudicated by independent cardiologists using MPI, blinded to biomarker measurements. Death and acute myocardial infarction (AMI) during follow-up were the prognostic endpoints. ResultsAmong 1142 consecutive patients inducible myocardial ischemia was found in 456 (40%) of all patients. For the detection of inducible myocardial ischemia, CJ before exercise stress testing (CJb) showed an area under the receiver-operating-characteristics curve (AUC) of 0.66 (95%CI 0.63–0.69), hs-cTnI 0.70 (95%CI 0.67–0.73, p=0.07 vs CJb), and BNP 0.66 (95%CI 0.62–0.69, p=0.98). The use of a dual-biomarker strategy combining hs-cTnI and BNP with CJb did not provide a significant advantage over the combination of hs-cTnI alone and CJb (AUC 0.74, 95%CI 0.72–0.77 vs AUC 0.74, 95%CI 0.71–0.77, p=0.16). Hs-cTnI showed good prognostic value for AMI (HR 1.6, 95%CI 1.3–1.9), and BNP for death (HR 1.6, 95%CI 1.3–2.1). ConclusionA dual-biomarker strategy combing BNP and hs-cTnI does not further increase diagnostic accuracy on top of clinical judgment and hs-cTnI alone. Summary and highlightsWe included 1142 consecutive patients with suspected inducible ischemia, and evaluated the added value of the biomarkers high-sensitivity cardiac troponin (hs-cTn) and B-type natriuretic peptide (BNP), alone and in combination, on top of clinical judgment. Clinical trial registrationBiochemical and Electrocardiographic Signatures in the Detection of Exercise-induced Myocardial Ischemia (BASEL VIII), NCT01838148, https://clinicaltrials.gov/ct2/show/NCT01838148

Effectiveness and safety of anti-ischemic trimetazidine in patients with stable angina pectoris and Type 2 diabetes.

Trimetazidine-based therapy was effective in stable coronary artery disease, with significant improvements from baseline (p<0.05) in: number of angina attacks/week (2.9±2.4 vs 1.1±1.6), angina severity (Canadian Cardiovascular Society Classification 1.9±0.8 vs 1.2±0.8), exercise capacity (metabolic equivalents 6.1±1.7 vs 6.5±1.7), and exercise-induced myocardial ischemia (min 5.5±2.5 vs 6.5±2.6). Trimetazidine treatment significantly (p<0.05) improved glucose metabolism, lowered HbA1c (7.1±1.1% vs 6.6±1.0%), glucose levels (7.7±2.1mmol/l vs 6.9±1.6mmol/l) and decreased arterial stiffness (pulse wave velocity 11.2±2.1m/s vs 10.4±2.2m/s). In most patients, the tolerability of trimetazidine was rated as excellent to good, with a low incidence of adverse events.

Positive and Negative Affect Is Related to Experiencing Chest Pain During Exercise-Induced Myocardial Ischemia.

Silent myocardial ischemia is thought to be associated with worse cardiovascular outcomes due to a lack of perception of pain cues that initiate treatment seeking. Negative affect (NA) has been associated with increased pain reporting and positive affect (PA) with decreased pain reporting, but these psychological factors have not been examined within the context of myocardial ischemia. This study evaluated the associations between PA, NA, and chest pain reporting in patients with and without ischemia during exercise testing. A total of 246 patients referred for myocardial perfusion single-photon emission computed tomography exercise stress testing completed the positive and negative affect schedule-expanded version, a measure of PA and NA. Presence of chest pain and myocardial ischemia were evaluated using standardized protocols. Logistic regression analyses revealed that for every 1-point increase in NA, there was a 13% higher chance for ischemic patients (odds ratio [OR] = 1.13; 95% confidence interval [CI] = 1.02 to 1.26) and an 11% higher chance in nonischemic patients (OR = 1.11; 95% CI = 1.03 to 1.19) to report chest pain. A significant interaction of PA and NA on chest pain reporting (β = 0.02; 95% CI = 0.002 to 0.031) was also observed; nonischemic patients with high NA and PA reported more chest pain (57%) versus patients with low NA and low PA (13%), with high NA and low PA (17%), and with high PA and low NA (7%). Patients who experience higher NA are more likely to report experiencing chest pain. In patients without ischemia, high NA and PA was also associated with a higher likelihood of reporting chest pain. Results suggest that high levels of PA as well as NA may increase the experience and/or reporting of chest pain.