1H NMR serum metabolomic profiling of patients at risk of cardiovascular diseases performing stress test

Abstract Cardiovascular diseases are the leading cause of death worldwide. Changes in lifestyle and/or pharmacological treatment are able to reduce the burden of coronary artery diseases (CAD) and early diagnosis is crucial for the timely and optimal management of the disease. Stress testing is a good method to measure the burden of CAD but it is time consuming and pharmacological testing may not fully mimic exercise test. The objectives of the present project were to characterize the metabolic profile of the population undergoing pharmacological and exercise stress testing to evaluate possible differences between them, and to assess the capacity of 1H NMR spectroscopy to predict positive stress testing. Pattern recognition was applied to 1H NMR spectra from serum of patients undergoing stress test and metabolites were quantified. The effects of the stress test, confounding variables and the ability to predict ischemia were evaluated using OPLS-DA. There was an increase in lactate and alanine concentrations in post-test samples in patients undergoing exercise test, but not in those submitted to pharmacological testing. However, when considering only pharmacological patients, those with a positive test result, showed increased serum lactate, that was masked by the much larger amount of lactate associated to exercise testing. In conclusion, we have established that pharmacological stress test does not reproduce the dynamic changes observed in exercise stress. Although there is promising evidence suggesting that 1H NMR based metabolomics could predict stress test results, further studies with much larger populations will be required in order to obtain a definitive answer.

Download Full-text

Abstract MP44: Assessment and Comparison of Six minute Walk Distance in Patients Undergoing Pharmacological Stress Test

Circulation ◽

10.1161/circ.129.suppl_1.mp44 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Azhar A Supariwala ◽

Seth Uretsky ◽

Randy Cohen ◽

Yathin Thammaiah ◽

Swathi Sangli ◽

...

Keyword(s):

Stress Testing ◽

Stress Test ◽

Exercise Stress ◽

Pharmacological Stress ◽

Walk Distance ◽

Stress Mode ◽

Objective Evidence ◽

Pharmacological Stress Test ◽

Minute Walk Distance ◽

Minute Walk

Background: Stress testing is widely used for diagnosis, risk stratification and prognosis of patients (pts). Although a normal stress study identifies pts at low risk, compared to exercise stress (Ex), those undergoing pharmacological stress test (PST) are at a higher risk of mortality. We studied the feasibility of a six minute walk test (SMWT) and compared the six-minute walk distance (SMWD) among Ex and PST. Methods: 328 consecutive patients [Ex=186 (57%); PST= 142 (43%)] referred for stress testing at our hospital were enrolled. Demographic and clinical information was collected. Each patient underwent a SMWT according to American Thoracic Society guidelines. Results: Patients in PST were older (62±14 vs. 57±12; p=0.001), had a higher BMI (36±30 vs. 29±6; p0.01), diabetes (46% vs. 25%; p<0.001) and hyperlipidemia (55% vs. 38%; p=0.01). We found a low SMWD achieved in PST (209 m ± 131) vs. Ex (366 m ± 107; p<0.001). When compared to age-gender matched healthy volunteer data, we found a significantly lower predicted SMWD in all patients suspected of CAD, with the lowest predicted SMWD in PST. (Figure) On multivariate analyses, patients undergoing PST had the highest risk (HR=10.1) of achieving lowest tertile of percent predicted SMWD, followed by female gender (HR=2.0), history of CHF, higher BMI. Only patients above 80 yrs of age had significant higher likelihood of undergoing pharmacological stress mode (OR = 7.2; 95CI =1.7 - 30.1; p=0.008). After including the interaction term for age and pharmacological stress mode, low SMWD among PST was seen in both older and young patients (p for interaction=0.46). Conclusion: SMWT is feasible in patients referred for PST. Patients with known or suspected CAD achieve a low percent predicted SMWD. This is the first study to show objective evidence of deconditioning in PST irrespective of co-morbidities. Future studies are needed to evaluate the prognostic significance of SMWT in patients undergoing pharmacological stress test.

Download Full-text

Comparison of Preoperative Assessment of Patient’s Metabolic Equivalents (METs) Estimated from History versus Measured by Exercise Cardiac Stress Testing

Anesthesiology Research and Practice ◽

10.1155/2018/5912726 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 3

Author(s):

Adam S. Weinstein ◽

Martin I. Sigurdsson ◽

Angela M. Bader

Keyword(s):

Cardiac Failure ◽

Stress Testing ◽

Stress Test ◽

Preoperative Evaluation ◽

Preoperative Assessment ◽

Exercise Stress ◽

Cardiac Stress ◽

Metabolic Equivalents ◽

Cardiac Stress Testing ◽

Cardiac Stress Test

Background. Preoperative anesthetic evaluations of patients before surgery traditionally involves assessment of a patient’s functional capacity to estimate perioperative risk of cardiovascular complications and need for further workup. This is typically done by inquiring about the patient’s physical activity, with the goal of providing an estimate of the metabolic equivalents (METs) that the patient can perform without signs of myocardial ischemia or cardiac failure. We sought to compare estimates of patients’ METs between preoperative assessment by medical history with quantified assessment of METs via the exercise cardiac stress test. Methods. A single-center retrospective chart review from 12/1/2005 to 5/31/2015 was performed on 492 patients who had preoperative evaluations with a cardiac stress test ordered by a perioperative anesthesiologist. Of those, a total of 170 charts were identified as having a preoperative evaluation note and an exercise cardiac stress test. The METs of the patient estimated by history and the METs quantified by the exercise cardiac stress test were compared using a Bland–Altman plot and Cohen’s kappa. Results. Exercise cardiac stress test quantified METs were on average 3.3 METS higher than the METs estimated by the preoperative evaluation history. Only 9% of patients had lower METs quantified by the cardiac stress test than by history. Conclusions. The METs of a patient estimated by preoperative history often underestimates the METs measured by exercise stress testing. This demonstrates that the preoperative assessments of patients’ METs are often conservative which errs on the side of patient safety as it lowers the threshold for deciding to order further cardiac stress testing for screening for ischemia or cardiac failure.

Download Full-text

Lactate Stress Testing in 155 Patients with Mitochondriopathy

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100001712 ◽

2002 ◽

Vol 29 (1) ◽

pp. 49-53 ◽

Cited By ~ 20

Author(s):

Josef Finsterer ◽

Erika Milvay

Keyword(s):

Sensitivity And Specificity ◽

Oxidative Metabolism ◽

Neurological Disorders ◽

Stress Testing ◽

Diagnostic Yield ◽

Stress Test ◽

High Sensitivity ◽

Serum Lactate ◽

Reference Limits ◽

Few Data

Objective:Few data are available about the diagnostic yield of the lactate stress test (LST) in a large group of patients with mitochondriopathy (MCP).Methods:Serum lactate was determined once before, three times during, and once after a 15-minute, constant 30W workload on a bicycle in 62 controls, aged 17 to 84 years, 155 patients with MCP, aged 17 to 87 years, and 31 patients with neurological disorders other than MCP.Results:Lactate's upper reference limits at rest, 5, 10, 15 minutes after starting, and 15 minutes after finishing the exercise were 2.0, 2.1, 2.1, 2.1 and 1.8 mmol/l respectively. The test was regarded abnormal if more than two of the five lactate values exceeded the cut-off levels. Among the 103 patients with abnormal LST, 64 (62 %) had normal resting lactate. The sensitivity of the test was 67% and the specificity 94%.Conclusion:The LST proved to have a high sensitivity and specificity in the detection of patients with MCP, being thus a simple but powerful tool to assess the impaired oxidative metabolism in MCP patients.

Download Full-text

Effects of polymorphisms in β1-adrenoceptor and α-subunit of G protein on heart rate and blood pressure during exercise test. The Finnish Cardiovascular Study

Journal of Applied Physiology ◽

10.1152/japplphysiol.00899.2005 ◽

2006 ◽

Vol 100 (2) ◽

pp. 507-511 ◽

Cited By ~ 25

Author(s):

Tuomo Nieminen ◽

Terho Lehtimäki ◽

Jarno Laiho ◽

Riikka Rontu ◽

Kari Niemelä ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Confidence Interval ◽

G Protein ◽

Exercise Test ◽

Odds Ratio ◽

Stress Test ◽

Exercise Stress ◽

Α Subunit ◽

Time Interaction

We tested whether the Arg389Gly and Ser49Gly polymorphisms of the β1-adrenergic receptor gene ADRB1 and the T393C polymorphism of the G protein α-subunit gene GNAS1 modulate heart rate (HR) and blood pressure responses during an exercise stress test. The study population comprised 890 participants (563 men and 327 women, mean age 58.1 ± 12.6 yr) of the Finnish Cardiovascular Study. Their HR, systolic (SAP), and diastolic arterial pressures (DAP) at rest, during exercise, and 4 min after the test were measured and analyzed by repeated-measurement ANOVA (RANOVA). Genotypes were detected by TaqMan 5′ nuclease assay. In all subjects, and in men and women separately, the T393C of GNAS1 was the only polymorphism with genotype × time interaction in HR over the three study phases ( P = 0.04, RANOVA). None of the polymorphisms presented genotype × time interaction in SAP or DAP responses ( P > 0.10, RANOVA). In all subjects at rest, the Ser49Gly polymorphism of ADRB1 tended ( P = 0.06, ANOVA) to differentiate HR. Arg389Gly polymorphism of ADRB1 affected maximal SAP during exercise ( P = 0.04, ANOVA) and the change in SAP from rest to maximal ( P = 0.03, ANOVA). Arg389 homozygotes, particularly men, were less likely to have ventricular extrasystoles during the exercise (odds ratio = 0.68, 95% confidence interval = 0.51–0.91, P = 0.009, and odds ratio = 0.60, 95% confidence interval = 0.42–0.86, P = 0.006, respectively) than did Gly389 carriers. In conclusion, polymorphisms examined appear to have modulatory effects on hemodynamics in a clinical exercise test setting. However, the effects in absolute numbers were minor and clinically possibly insignificant.

Download Full-text

Low Cost Magnetic Resonance Imaging-Compatible Stepper Exercise Device for Use in Cardiac Stress Tests

Journal of Medical Devices ◽

10.1115/1.4027343 ◽

2014 ◽

Vol 8 (4) ◽

Cited By ~ 4

Author(s):

Omid Forouzan ◽

Evan Flink ◽

Jared Warczytowa ◽

Nick Thate ◽

Andrew Hanske ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Low Cost ◽

Stress Test ◽

Exercise Stress ◽

Resonance Imaging ◽

Pharmacological Stress ◽

Cardiac Stress ◽

Adjustable Weight ◽

Cardiac Stress Test

Cardiovascular disease is the leading cause of death worldwide. Many cardiovascular diseases are better diagnosed during a cardiac stress test. Current approaches include either exercise or pharmacological stress echocardiography and pharmacological stress magnetic resonance imaging (MRI). MRI is the most accurate noninvasive method of assessing cardiac function. Currently there are very few exercise devices that allow collection of cardiovascular MRI data during exercise. We developed a low-cost exercise device that utilizes adjustable weight resistance and is compatible with magnetic resonance (MR) imaging. It is equipped with electronics that measure power output. Our device allows subjects to exercise with a leg-stepping motion while their torso is in the MR imager. The device is easy to mount on the MRI table and can be adjusted for different body sizes. Pilot tests were conducted with 5 healthy subjects (3 male and 2 female, 29.2 ± 3.9 yr old) showing significant exercise-induced changes in heart rate (+42%), cardiac output (+40%) and mean pulmonary artery (PA) flow (+%49) post exercise. These data demonstrate that our MR compatible stepper exercise device successfully generated a hemodynamically stressed state while allowing for high quality imaging. The adjustable weight resistance allows exercise stress testing of subjects with variable exercise capacities. This low-cost device has the potential to be used in a variety of pathologies that require a cardiac stress test for diagnosis and assessment of disease progression.

Download Full-text

A Method for Predicting the Main Indicators of Cardiopulmonary Stress Testing for Patients with Chronic Heart Failure

Journal of the Russian Universities Radioelectronics ◽

10.32603/1993-8985-2020-23-1-96-104 ◽

2020 ◽

Vol 23 (1) ◽

pp. 96-104

Author(s):

A. S. Krasichkov ◽

E. Mbazumutima ◽

F. Shikama ◽

E. M. Nifontov

Keyword(s):

Heart Failure ◽

Oxygen Consumption ◽

Chronic Heart Failure ◽

Stress Testing ◽

Stress Test ◽

Significant Risk ◽

Exercise Stress Test ◽

Exercise Stress ◽

Peak Oxygen Consumption ◽

Prognostic Information

Introduction. Cardiopulmonary stress test provides significant diagnostic and prognostic information of the condition of patients with cardiovascular and pulmonary diseases. There is a serious problem, that final phase of stress testing is a physically difficult exercise for a person. There is a significant risk of occurrence and development of pathological conditions of the patient's cardiovascular system. One of the solutions is the development of methods for assessing the biological parameters of the patients at the end of a load protocol based on data from the initial stages of the test.Aim. Development of a method for finding an estimate of the maximum heart rate (HR) and of the peak oxygen consumption (OC) for the patients with chronic heart failure at the end of a cardiorespiratory exercise stress test, based on the results of the study obtained at the first initial stages of the test.Materials and methods. For the study, 149 anonymized records of rhythmograms and data of changes in the oxygen consumption of the patients with chronic heart failure were used. The patients underwent a cardiopulmonary stress test by a bicycle ergometer using step-by-step load protocol (the load power increase at each stage was 10 W, the duration of the load stage was 1 min)Results. Based on the analysis of the data obtained, a method for assessing the peak values of HR and of PC of the patients with chronic heart failure was developed.Conclusion. The relative error of the proposed estimate of the HR peak in most cases was no more than 10 %, which allows it to be used for practical purposes. It was established that when performing 70 % of the stress protocol, the error of the proposed estimate of the OC peak in most cases did not exceed 20 %. More research is needed to improve the accuracy of the assessment for using in medical applications aimed to the modernization of methods and equipment for stress testing of the patients.

Download Full-text

Emergency department patient compliance with follow-up for outpatient exercise stress testing: a randomized controlled trial

CJEM ◽

10.1017/s1481803500015463 ◽

2007 ◽

Vol 9 (06) ◽

pp. 435-440 ◽

Cited By ~ 24

Author(s):

Doug Richards ◽

Nazanin Meshkat ◽

Jaqueline Chu ◽

Kevin Eva ◽

Andrew Worster

Keyword(s):

Chest Pain ◽

Stress Testing ◽

Stress Test ◽

Intervention Group ◽

Exercise Stress Test ◽

Low Risk ◽

Exercise Stress ◽

Exercise Stress Testing ◽

Control Group

ABSTRACTIntroduction:Numerous patients are assessed in the emergency department (ED) for chest pain suggestive of acute coronary syndrome (ACS) and subsequently discharged if found to be at low risk. Exercise stress testing is frequently advised as a follow-up investigation for low-risk patients; however, compliance with such recommendations is poorly understood. We sought to determine if compliance with follow-up for exercise stress testing is higher in patients for whom the investigation is ordered at the time of ED discharge, compared with patients who are advised to arrange testing through their family physician (FP).Methods:Low-risk chest pain patients being discharged from the ED for outpatient exercise stress test and FP follow-up were randomized into 2 groups. ED staff ordered an exercise stress test for the intervention group, and the control group was advised to contact their FP to arrange testing. The primary outcome was completion of an exercise stress test at 30 days, confirmed through both patient contact and stress test results. Patients were unaware that our primary interest was their compliance with the exercise stress testing recommendations.Results:Two-hundred and thirty-one patients were enrolled and baseline characteristics were similar between the 2 groups. Completion of an exercise stress test at 30 days occurred in 87 out of 120 (72.5%) patients in the intervention group and 60 out of 107 (56.1%) patients in the control group. The difference in compliance rates (16.4%) between the 2 groups was statistically significant (χ2= 6.69,p< 0.001) with a relative risk of 1.29 (95% confidence interval 1.18–1.40), and the results remained significant after a “worst case” sensitivity analysis involving 4 control group cases lost to follow-up. When subjects were contacted by telephone 30 days after the ED visit, 60% of those who were noncompliant patients felt they did not have a heart problem and that further testing was unnecessary.Conclusion:When ED staff order an outpatient exercise stress test following investigation for potential ACS, patients are more likely to complete the test if it is booked for them before ED discharge. After discharge, many low-risk chest pain patients feel they are not at risk and do not return to their FP for further testing in a timely manner as advised. Changing to a strategy of ED booking of exercise stress testing may help earlier identification of patients with coronary heart disease.

Download Full-text

Abstract P326: Myocardial Ischemia and Mobilization of Circulating Progenitor Cells

Circulation ◽

10.1161/circ.135.suppl_1.p326 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Muhammad Hammadah ◽

Ayman Samman Tahhan ◽

Ibhar Almheid ◽

Bryan Ross Kindya ◽

Mazen Ghafeer ◽

...

Keyword(s):

Myocardial Infarction ◽

Myocardial Perfusion ◽

Myocardial Ischemia ◽

Progenitor Cells ◽

Linear Models ◽

Stress Test ◽

Exercise Stress ◽

Previous Myocardial Infarction ◽

Pharmacological Stress ◽

Pharmacological Stress Test

Background: Circulating progenitor cells (CPCs) are involved in vascular repair and regeneration. Low levels of CPCs in patients with CAD have been linked to adverse cardiovascular outcomes. The response of CPCs to transient myocardial ischemia in patients with CAD has not been studied before. We aimed to investigate the CPC response to exercise provoked myocardial ischemia (demand ischemia), and compare it to myocardial ischemia detected during pharmacological stress test (flow mismatch). Methods: 570 patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging during exercise (69%), or pharmacological stress (31%). myocardial ischemia was defined as a new or worsening impairment in myocardial perfusion using a 17-segment model. CD34+ CPCs were enumerated by flow cytometry at rest and 30 min after stress testing. The change in CPC count was compared between patients with and without myocardial ischemia using mixed linear models. Results: Mean age was 63±9 years, 76% males, 36% with previous myocardial infarction. The incidence of myocardial ischemia was 31% and 41% during exercise and pharmacological stress test, respectively. No difference was observed in resting CPC between patients undergoing exercise vs pharmacological stress test, nor between patients with or without myocardial ischemia. However, patients who developed myocardial ischemia during exercise stress had a significant decrease in CPC with stress in comparison to those without myocardial ischemia (-12% vs 4%, respectively, p=0.006). Furthermore, the change in CPCs was inversely correlated with the magnitude of myocardial ischemia (R=-0.13, p=0.023), suggesting a greater CPC reduction with larger ischemic burden. These findings remained significant even after adjustment for age, gender, race, BMI, previous myocardial infarction, resting levels of CPCs and hematocrit change with stress. No difference was observed in CPC response to pharmacological stress test (change of -1% vs 3%, for patients with and without myocardial ischemia, respectively, p=0.96). Conclusion: Exercise stress-induced myocardial ischemia is associated with a decrease in CPC counts, likely due to increased homing of stem cells to the ischemic myocardium. Whether the extent of CPC uptake has prognostic implication, or whether the CPC response can be altered with intervention needs further investigation.

Download Full-text

Theophylline and Caffeine as Alternatives During an Aminophylline Shortage

Annals of Pharmacotherapy ◽

10.1177/1060028018806624 ◽

2018 ◽

Vol 53 (3) ◽

pp. 316-320 ◽

Cited By ~ 2

Author(s):

Emily L. Singleton ◽

Nancy Le ◽

Genevieve Lynn Ness

Keyword(s):

Stress Testing ◽

Stress Test ◽

Pharmacological Stress ◽

Drug Shortage ◽

Reversal Agent ◽

Cardiac Stress ◽

Reversal Agents ◽

Diagnosis And Prognosis ◽

Pharmacological Stress Testing ◽

Pharmacological Stress Test

The latest aminophylline shortage has prompted a need for alternative reversal agents for pharmacological stress testing. Cardiac stress testing is common for diagnosis and prognosis in patients with coronary heart disease. Options for pharmacological stress test agents include adenosine, regadenoson, dipyridamole, and dobutamine, whereas aminophylline is the recommended reversal agent. Adenosine and dobutamine can be used as alternatives to regadenoson and dipyridamole to decrease or eliminate the use of aminophylline. Alternatives to aminophylline include theophylline and caffeine. It is important to efficiently identify alternatives during a drug shortage to maintain optimal patient outcomes.

Download Full-text

The Response of Circulating Leptin Levels to Exercise Stress Testing in Subjects Diagnosed with Metabolic Syndrome

ISRN Endocrinology ◽

10.1155/2014/689260 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5

Author(s):

Dana Pop ◽

Alexandra Dădârlat ◽

Gyorgy Bodizs ◽

Liana Stanca ◽

Dumitru Zdrenghea

Keyword(s):

Metabolic Syndrome ◽

Stress Testing ◽

Stress Test ◽

False Negative ◽

Test Group ◽

Exercise Stress ◽

Exercise Stress Testing ◽

True Negative ◽

Negative Test ◽

Group 2

Aim. To assess the plasma leptin responses after exercise stress testing in patients with metabolic syndrome (MS). Material and Methods. We investigated 67 patients with MS, with mean age of 55±7 years. They underwent exercise stress testing on cycloergometer. The lot was divided into three groups: group 1—10 patients with a true positive test, group 2—18 patients with a true negative test, and group 3—39 patients with a false negative test. Leptin levels were measured using the ELISA method. Results. Leptin levels decreased after effort in patients with MS (9.42±11.08 ng/mL before and 8.18±11.5 ng/mL after the exercise stress test, P=0.0005, r=0.874). In groups 1 (8.98±9.09 at rest versus 5.98±8.73 ng/mL after the exercise test, P=0.002) and 3 (8.6±10.53 at rest versus 6.91 ± 9.07 ng/mL, P=0.0005), lower leptin levels were recorded immediately after exercise testing. Leptin levels were not significantly lower in group 2 before effort (9.49±11.36 ng/ml) and after (9.46±13.81 ng/mL). We found no correlation between leptinemia and exercise stress testing parameters, regardless of group. Conclusion. Our research showed that short-term exercise lowers leptin levels in coronary patients, without a relationship between its parameters and leptin values.

Download Full-text