Adenosine Stress Testing Research Articles

Complications of exercise and pharmacologic stress echocardiography.

Stress echocardiography is a diagnostic cardiovascular exam that is commonly utilized for multiple indications, including but not limited to the assessment of obstructive coronary artery disease, valvular disease, obstructive hypertrophic cardiomyopathy, and diastolic function. Stress echocardiography can be performed via both exercise and pharmacologic modalities. Exercise stress is performed with either treadmill or bicycle-based exercise. Pharmacologic stress is performed via either dobutamine or vasodilator-mediated (i.e., dipyridamole, adenosine) stress testing. Each of these modalities is associated with a low overall prevalence of major, life-threatening adverse outcomes, though adverse events are most common with dobutamine stress echocardiography. In light of the recent COVID-19 pandemic, the risk of infectious complications to both the patient and stress personnel cannot be negated; however, when certain precautions are taken, the risk of infectious complications appears minimal. In this article, we review each of the stress echocardiographic modalities, examine major potential adverse outcomes and contraindications, assess the risks of stress testing in the setting of a global pandemic, and examine the utilization and safety of stress testing in special patient populations (i.e., language barriers, pediatric patients, pregnancy).

Reference values of myocardial native T1 and extracellular volume in patients without structural heart disease and had negative 3T cardiac magnetic resonance adenosine stress test.

To establish the reference values of native T1 and extracellular volume (ECV) in patients without structural heart disease and had a negative adenosine stress 3T cardiac magnetic resonance. Short-axis T1 mapping images were acquired using a modified Look-Locker inversion recovery technique before and after administration of 0.15mmol/kg gadobutrol to calculate both native T1 and ECV. To compare the agreement between measurement strategies, regions of interest (ROI) were drawn in all 16 segments then averaged to represent mean global native T1. Additionally, an ROI was drawn in the mid-ventricular septum on the same image to represent the mid-ventricular septal native T1. Fifty-one patients (mean 65years, 65% women) were included. Mean global native T1 averaged from all 16 segments and a mid-ventricular septal native T1 were not significantly different (1221.2±35.2 vs 1228.4±43.7ms, p=0.21). Men had lower mean global native T1 (1195±29.8 vs 1235.5±29.4ms, p<0.001) than women. Both mean global and mid-ventricular septal native T1 were not correlated with age (r=0.21, p=0.13 and r=0.18, p=0.19, respectively). The calculated ECV was 26.6±2.7%, which was not influenced by either gender or age. We report the first study to validate the native T1 and ECV reference ranges, factors influencing T1, and the validation across measurement methods in older Asian patients without structural heart disease and had a negative adenosine stress test. These references allow for better detection of abnormal myocardial tissue characteristics in clinical practice.

Adenosine-Induced Myocardial Ischemia in a Patient with Myocardial Bridge

The adenosine stress test and exercise stress test have been widely used in the diagnosis of coronary heart disease, which has high sensitivity and specificity for diagnosis of coronary heart disease. The myocardial bridge is a congenital dysplasia of the coronary artery which may cause severe myocardial ischemia, acute myocardial infarction, arrhythmia, and sudden death. Although drug therapy for this disease is clear and widely used, indication for open-chest surgery is still vague. This case shows a patient with long-term chest pain undergoing the coronary computed tomographic angiography in our hospital 1 month ago, which showed the mild myocardial bridge in the left anterior descending (LAD) branch. Then, she did the mental stress-induced myocardial ischemia and cardiopulmonary exercise test which the results were negative. After the informed consent, the patient took the adenosine stress test and severe angina occurred during the test. Later, coronary angiography showed that the myocardial bridge caused 70% contraction of the middle segment of the LAD branch. In the case of long-term ineffective drug treatment, the patient underwent a open-chest surgery called coronary artery myotomy and her chest discomfort eventually recovered. To a degree, adenosine stress test may be more sensitive than exercise stress test in predicting the severity of coronary artery stenosis. Moreover, we may provide a unique direction of indication for surgeons to operate open-chest surgery on the myocardial bridge.

Detection of increased pyruvate dehydrogenase flux in the human heart during adenosine stress test using hyperpolarized [1-13C]pyruvate cardiovascular magnetic resonance imaging

BackgroundHyperpolarized (HP) [1-13C]pyruvate cardiovascular magnetic resonance (CMR) imaging can visualize the uptake and intracellular conversion of [1-13C]pyruvate to either [1-13C]lactate or 13C-bicarbonate depending on the prevailing metabolic state. The aim of the present study was to combine an adenosine stress test with HP [1-13C]pyruvate CMR to detect cardiac metabolism in the healthy human heart at rest and during moderate stress.MethodsA prospective descriptive study was performed between October 2019 and August 2020. Healthy human subjects underwent cine CMR and HP [1-13C]pyruvate CMR at rest and during adenosine stress. HP [1-13C]pyruvate CMR images were acquired at the mid-left-ventricle (LV) level. Semi-quantitative assessment of first-pass myocardial [1-13C]pyruvate perfusion and metabolism were assessed. Paired t-tests were used to compare mean values at rest and during stress.ResultsSix healthy subjects (two female), age 29 ± 7 years were studied and no adverse reactions occurred. Myocardial [1-13C]pyruvate perfusion was significantly increased during stress with a reduction in time-to-peak from 6.2 ± 2.8 to 2.7 ± 1.3 s, p = 0.02. This higher perfusion was accompanied by an overall increased myocardial uptake and metabolism. The conversion rate constant (kPL) for lactate increased from 11 ± 9 *10–3 to 20 ± 10 * 10–3 s−1, p = 0.04. The pyruvate oxidation rate (kPB) increased from 4 ± 4 *10–3 to 12 ± 7 *10–3 s−1, p = 0.008. This increase in carbohydrate metabolism was positively correlated with heart rate (R2 = 0.44, p = 0.02).ConclusionsAdenosine stress testing combined with HP [1-13C]pyruvate CMR is feasible and well-tolerated in healthy subjects. We observed an increased pyruvate oxidation during cardiac stress. The present study is an important step in the translation of HP [1-13C]pyruvate CMR into clinical cardiac imaging.Trial registration EUDRACT, 2018-003533-15. Registered 4th of December 2018, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-003533-15

Reference Values of Myocardial Native T1 and Extracellular Volume in Patients Without Structural Heart Disease and Had Negative 3T Cardiac Magnetic Resonance Adenosine Stress Test

Reference Values of Myocardial Native T1 and Extracellular Volume in Patients Without Structural Heart Disease and Had Negative 3T Cardiac Magnetic Resonance Adenosine Stress Test

Linear concentration-response relationship of serum caffeine with adenosine-induced fractional flow reserve overestimation: a comparison with papaverine.

Caffeine intake from one cup of coffee one hour before adenosine stress tests, corresponding to serum caffeine levels of 3-4 mg/L, is thought to be acceptable for non-invasive imaging. We aimed to elucidate whether serum caffeine is independently associated with adenosine-induced fractional flow reserve (FFR) overestimation and their concentration-response relationship. FFR was measured using adenosine (FFRADN) and papaverine (FFRPAP) in 209 patients. FFRADN overestimation was defined as FFRADN - FFRPAP. The locally weighted scatterplot smoothing (LOWESS) approach was applied to evaluate the relationship between serum caffeine level and FFRADN overestimation. Multiple regression analysis was used to determine independent factors associated with FFRADN overestimation. Caffeine was ingested at <12 hours in 85 patients, at 12-24 hours in 35 patients, and at >24 hours in 89 patients. Multiple regression analysis identified serum caffeine level as the strongest factor associated with FFRADN overestimation (p<0.001). The LOWESS curve demonstrated that FFRADN overestimation started from just above the lower detection limit of serum caffeine and increased approximately 0.01 FFR unit per 1 mg/L increase in serum caffeine level with a linear relationship. The 90th percentile of serum caffeine levels for the ≤12-hour, the 12-24-hour, and the >24-hour groups corresponded to FFRADN overestimations by 0.06, 0.03, and 0.02, respectively. Serum caffeine overestimates FFRADN values in a linear concentration-response manner. FFRADN overestimation occurs at much lower serum caffeine levels than those that were previously believed. Our results highlight that standardised caffeine control is required for reliable adenosine-induced FFR measurements.

Fast-Strain Encoded Cardiac Magnetic Resonance During Vasodilator Perfusion Stress Testing.

Background: Cardiac magnetic resonance perfusion imaging during vasodilator stress is an established modality in patients with suspected and known coronary artery disease (CAD).Aim: This study aimed to evaluate the performance of fast-Strain-Encoded-MRI (fast-SENC) for the diagnostic classification and risk stratification of patients with ischemic heart disease.Methods: Perfusion and fast-SENC cardiac magnetic resonance (CMR) images were retrospectively analyzed in 111 patients who underwent stress CMR. The average myocardial perfusion score index, global and segmental longitudinal and circumferential strain (GLS and GCS and SLS and SCS, respectively), were measured at rest and during stress. The combination of SLS and SCS was referred to as segmental aggregate strain (SAS). Segments exhibiting perfusion defects or SAS impairment during stress were defined as “ischemic.” All-cause mortality, non-fatal infarction, and urgent revascularization were deemed as our combined clinical endpoint.Results: During adenosine stress testing, 44 of 111 (39.6%) patients exhibited inducible perfusion abnormalities. During a mean follow-up of 1.94 ± 0.65 years, 25 (22.5%) patients reached the combined endpoint (death in n = 2, infarction in n = 3 and urgent revascularization in n = 20). Inducible perfusion defects were associated with higher number of segments with inducible SAS reduction ≥6.5% (χ2 = 37.8, AUC = 0.79, 95% CI = 0.71–0.87, p < 0.001). In addition, patients with inducible perfusion defects or SAS impairment exhibited poorer outcomes (AUCPerf = 0.81 vs. AUCSAS = 0.74, p = NS vs. each other, and χ2 = 30.8, HR = 10.3 and χ2 = 9.5, HR = 3.5, respectively, p < 0.01 for both).Conclusion: Purely quantitative strain analysis by fast-SENC during vasodilator stress was related to the diagnosis of ischemia by first-pass perfusion and is non-inferior for the risk stratification of patients with ischemic heart disease. This may bear clinical implications, especially in patients with contraindications for contrast agent administration.

Human hyperpolarized [1-13C] pyruvate CMR and adenosine stress test

Abstract Background Hyperpolarized (HP) [1-13C]pyruvate cardiac magnetic resonance (CMR) imaging can visualize myocardial perfusion and metabolism beyound glucose uptake. Depending on the prevailing metabolic conditions, buid-up of either [1-13C]lactate or 13C-bicarbonate can be measured. The aim of the present study was to assess cardiac metabolism using HP [1-13C]pyruvate rest-stress CMR. Methods Six healthy volunteers underwent cine CMR and HP [1-13C]pyruvate CMR at rest and during an adenosine stress test. Signal from HP [1-13C]pyruvate and its downstream metabolites was measured at the mid-left-ventricle (LV) level. We did semi-quantitative assessment of first-pass myocardial [1-13C]pyruvate perfusion. Pressure-volume loops were assessed non-invasively. Results Myocardial [1-13C]pyruvate perfusion was significantly increased during stress with a reduction in time-to-peak from 6.2±2.8 sec to 2.7±1.3 sec, p=0.04. This higher perfusion was accompanied by an overall increased myocardial uptake and metabolism. The conversion rate constant (kPL) for lactate increased from 0.011±0.009 sec–1 to 0.020±0.010 sec–1, p=0.04. The pyruvate oxidation (kPB) increased from 0.004±0.004 sec–1 to 0.012±0.007 sec–1, p=0.008. This increase in oxidative metabolism was positively correlated with heart rate (R2=0.44, p=0.02). Conclusion We observed a significant increase in carbohydrate oxidation during cardiac stress in the healthy human heart. The present study forms the basis for comparisons in future research in patients with heart failure and coronary artery disease. HP [1-13C]pyruvate CMR could be a possible alternative to PET in the future. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Danish Heart FoundationIndependent Research Fund, Denmark Increased conversion rate of pyruvateIncreased metabolite signal in LV

Selective Adenosine A2A Agonists May Change Myocardial Perfusion Imaging.

In recent years, the requirement for pharmacological stress myocardial perfusion imaging (SPECT) has increased, and adenosine stress testing is now the mainstream. Selective adenosine A2A receptor agonists will be applied clinically in the future. By selectively activating only A2A receptors, it can reduce complications such as bronchospasm, hypotension, and bradycardia, which have been problems with adenosine stress tests. In addition, since this drug can be administered in bolus injection, it has the advantage of being able to perform the test at one root.

The role of stress-induced dyssynchrony obtained from nuclear modalities in evaluation of high-risk patients after surgical treatment of ischemic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Background Mechanical dyssynchrony (MD) is a well-known parameter witch has prognostic value [1]. Stress tests can be used to unmask MD. However, stress-induced changes in left ventricle (LV) MD by data of nuclear imaging modalities are not well-understood, especially its predictive value [2]. Purpose. To assess the role of stress-induced changes of LV MD obtained by nuclear modalities in evaluating high-risk patients after surgical treatment of ischemic cardiomyopathy (ICM). Methods. Sixty-nine patients with ICM were enrolled. Before surgical treatment all patients underwent gated myocardial perfusion imaging (gMPI) (Tc99m-MIBI; 2 days stress-rest protocol, adenosine 140mkg/kg/min) and gated blood pool SPECT (gBPS) (rest – stress, dobutamine doses of 5/10/15 µg/kg/min). After surgical treatment patients were divided into 2 groups: with (n = 21) and without (n = 48) complicated course of early postoperative period (death, intra-aortic balloon pump, extra inotropic support). The following parameters were estimated: summed stress score (SSS), summed rest score (SRS), summed different score (SDS); phase mean, phase standard deviation (PSD) and histogram bandwidth (HBW) (% from cycle for MPI; degrees for gBPS); phase entropy (%, only by gBPS). Stress-induced changes (Δ) were calculated for MPI indices as [stress value-rest value], for gBPS indices as [value on each dobutamine dose-rest value]. For gBPS the maximum changes of MD were calculated as well. Results. Rest gBPS MD correlated with SRS better than rest gMPI (gMPI: PSD r = 0.31, p = 0.005; HBW r = 0.28, p = 0.008; gBPS: PSD r = 0.47, p &amp;lt; 0.001; HBW r = 0.36, p = 0.006; entropy r = 0.39, p = 0.003). Stress gBPS MD correlated better with post stress gMPI MD at the dobutamine dose of 5µg/kg/min. An following increase of the dobutamine dose led to a decrease in the r-value, but it remained significant for all indices (tab.1). Stress-induced MD changes didn’t correlate between gMPI and gBPS. Mann-Whitney test showed significant differences in SDS (p = 0.02) between the groups. Both methods didn’t show any differences at rest study. Stress-induced changes of MD showed differences between groups in only ΔEntropy rest-10µg/kg/min (p = 0.02) and maximum ΔEntropy (p = 0.01) by gBPS, as well as Δphase mean (p = 0.03) by gMPI. Logistic regression analysis showed that only maximum ΔEntropy has prognostic value in prediction of the course of early postoperative period (OR 1.2 95%CI 1.04; 1.37). ROC-analysis showed sensitivity of 80% and specificity of 55% with AUC of 0.7 for cut-off value &amp;gt;0. Conclusion. LVMD obtained from gBPS is associated with SRS better than those obtained from gMPI. Dyssynchrony indices obtained from gMPI with adenosine stress-test have a week to moderate correlation with those obtained from dobutamine gBPS, and correlation decrease with increasing of dobutamine dose. Only maximum ΔEntropy obtained from dobutamine gBPS is associated with the adverse course of early postoperative period in patients with ICM.

Ferumoxytol-enhanced magnetic resonance T1 reactivity for depiction of myocardial hypoperfusion.

Myocardial T1 reactivity, defined as the relative change in T1 between rest and vasodilator-induced stress, has been proposed as a magnetic resonance imaging (MRI) biomarker of tissue perfusion. We hypothesize that the superparamagnetic iron-oxide nanoparticle, ferumoxytol, sensitizes T1 to changes in the intramyocardial vascular compartment and improves the sensitivity and specificity of T1 reactivity as an imaging biomarker of tissue perfusion. We aim to assess the diagnostic performance of ferumoxytol-enhanced (FE) myocardial T1 reactivity in swine models of myocardial hypoperfusion. We induced acute myocardial hypoperfusion in 13 swine via percutaneous, transcatheter deployment of a 3D printed intracoronary stenosis implant into the left anterior descending coronary artery. We performed native and FE adenosine stress testing using 5(3)3(3)3 MOLLI and SASHA T1 mapping sequences with bSSFP readout on a clinical 3.0 T magnet. MOLLI T1 maps were fitted using both the conventional MOLLI and the Instantaneous Signal Loss (InSiL) T1-fitting algorithms. Regardless of the MOLLI or SASHA pulse sequence or T1-fitting algorithm, ferumoxytol contrast increased the dynamic range of T1 reactivity in both the remote and ischemic myocardial regions. Relative to remote myocardium, native and FE T1 reactivity were blunted in ischemic myocardium (p < 0.05) with InSiL-MOLLI, MOLLI and SASHA. An InSiL-MOLLI-derived FE T1 reactivity threshold of -4.65% had 73.3% sensitivity and 96.2% specificity for prediction of regional wall motion abnormalities (AUC 0.915, 95% CI 0.786-0.979), whereas a SASHA-derived FE T1 reactivity threshold of -5.25% had 75.0% sensitivity and 95.2% specificity (AUC 0.905, 95% CI 0.751-0.979). Ferumoxytol significantly increased the dynamic range of T1 reactivity as a measure of myocardial hypoperfusion in vasodilator stress T1 mapping studies. FE T1 reactivity maps can be used to quantitatively distinguish ischemic and remote myocardium with high specificity in swine models of acute myocardial hypoperfusion.

A case of bronchospasm-induced takotsubo cardiomyopathy during adenosine stress testing

A case of bronchospasm-induced takotsubo cardiomyopathy during adenosine stress testing

Guidance and Best Practices for Nuclear Cardiology Laboratories During the COVID-19 Pandemic: An Information Statement From ASNC and SNMMI.

Guidance and Best Practices for Nuclear Cardiology Laboratories During the COVID-19 Pandemic: An Information Statement From ASNC and SNMMI.

Considerations for Stress Testing Performed in Conjunction with Myocardial Perfusion Imaging.

For myocardial perfusion imaging (MPI), the best test to evaluate hemodynamic changes during stress is an exercise treadmill test. It provides independent prognostic value, including evaluation of total exercise time, performance, and capacity; heart rate response during exercise, with ischemia, and in recovery; blood pressure response; myocardial oxygen demand; and assessment of symptoms. Combining these exercise data with perfusion imaging provides the best prognostic value and risk stratification for patients. Although exercise stress testing accompanied by MPI is preferential, it is not always possible since an increasing number of patients cannot exercise to a maximal (symptom-limited) level. Further, there is much evidence in the literature demonstrating a suboptimal, non-symptom-limited (not achieving at least 4-6 min or <85% of maximum predicted heart rate) exercise test performed as part of an MPI study may result in a false-negative outcome. Therefore, pharmacologic stress agents provide an excellent alternative for those patients who cannot achieve an adequate heart rate response or adequately perform physical exercise. This article focuses on considerations for performing stress (exercise and pharmacologic) testing in conjunction with MPI. It is meant to provide a basic overview of the principles of exercise stress testing; discuss the indications, contraindications, patient preparation, and protocols for exercise stress testing; discuss the contraindications, administration protocols, and side effects for vasodilator (adenosine, dipyridamole, and regadenoson) stress testing; and discuss the contraindications, administration protocols, and side effects for dobutamine stress testing.

The feasibility and safety of graded adenosine stress test for myocardial perfusion in asthmatic and/or COPD patients.

A total of 40 patients (M:F::26:14; age range: 37-84yrs; mean: 64.1yrs) with known chronic obstructive pulmonary disease (COPD) (ranging from mild to severe), referred for a stress myocardial perfusion study, were included in this study over a period of one year. All patients underwent adenosine stress in a titrated protocol and pre-infusion of short acting bronchodilator salbutamol 2 puffs few minutes prior to start adenosine infusion. In a fraction of 26 patients, pulmonary function tests (PFT) were performed and used in addition to clinical examination to classify the severity of pulmonary obstruction. On the basis of forced expiratory volume in one second (FEV1) on PFT, 4 patients had a mild disease (FEV1 60%-80%), 17 had a moderate obstructive disease (FEV1 41%-59%) and 4 had severe COPD/asthma (FEV1 <40%) while 2 patients had normal >95% FEV1. Post-stress questionnaire to assess subjective tolerance and symptoms were undertaken for all patients. The results demonstrated an excellent tolerance to adenosine infusion in this group of patients, with adequate stress achieved in all. None had complaints of severe dyspnoea or respiratory distress requiring medical intervention. Thirteen patients had mild to moderate degree dyspnoea during infusion. The study included a significant number of 23 elderly patients (>65 years), who showed better tolerance than the younger patients. In this pilot study in patients with COPD who referred for myocardial perfusion scintigraphy, the feasibility and safety of adenosine in a graded protocol along with a good pre-stress assessment and a short acting bronchodilator treatment was documented.

Cardiac perfusion and function after high-intensity exercise training in late premenopausal and recent postmenopausal women: an MRI study.

We examined the influence of recent menopause and aerobic exercise training in women on myocardial perfusion, left ventricular (LV) dimension, and function. Two groups (n = 14 each) of healthy late premenopausal (50.2 ± 2.1 yr) and recent postmenopausal (54.2 ± 2.8 yr) women underwent cardiac magnetic resonance imaging (cMRI) at baseline and after 12 wk of high-intensity aerobic training. Measurements included LV morphology, systolic function, and myocardial perfusion at rest and during an adenosine stress test. At baseline, resting myocardial perfusion was lower in the postmenopausal than the premenopausal group (77 ± 3 vs. 89 ± 3 ml·100 g-1·min-1; P = 0.01), while adenosine-induced myocardial perfusion was not different (P = 0.81). After exercise training, resting myocardial perfusion was lower in both groups (66 ± 2; P = 0.002 vs. 81 ± 3 ml·100 g-1·min-1; P = 0.03). The adenosine-induced change in myocardial perfusion was lower in the groups combined (by 402 ± 17 ml·100 g-1·min-1; P = 0.02), and the adenosine-induced increase in heart rate was 10 ± 2 beats/min lower (P < 0.0001) in both groups after training. Normalization of myocardial perfusion using an estimate of cardiac work eliminated the differences in perfusion between the premenopausal and postmenopausal groups and the effect of training. Left ventricle mass was higher in both groups (P = 0.03; P = 0.006), whereas LV end-diastolic (P = 0.02) and stroke (P = 0.045) volumes were higher in the postmenopausal group after training. Twelve weeks of exercise training increased left ventricle mass and lowered resting and adenosine-induced myocardial perfusion, an effect that was likely related to cardiac work. The current data also suggest that the early menopausal transition has limited impact on cardiac function and structure. NEW & NOTEWORTHY This study provides for the first time estimates of myocardial perfusion in late premenopausal and recent postmenopausal women before and after a period of intense aerobic training. Resting myocardial perfusion was lower in postmenopausal than premenopausal women. Training lowered myocardial resting and stress perfusion in both groups, an effect that was likely influenced by the lower heart rate.

Future cardiac events in patients with ischemic ECG changes during adenosine infusion as a myocardial stress agent and normal cardiac scan.

We sought to determine the prognostic importance of adenosine-induced ischemic ECG changes in patients with normal single-photon emission computed tomography myocardial perfusion images (MPI). We carried out a retrospective analysis of 765 patients undergoing adenosine MPI between January 2013 and January 2015. Patients with baseline ECG abnormalities and/or abnormal scan were excluded. Overall, 67 (8.7%) patients had ischemic ECG changes during adenosine infusion in the form of ST depression of 1 mm or more. Of these, 29 [43% (3.8% of all patients)] had normal MPI (positive ECG group). An age-matched and sex-matched group of 108 patients with normal MPI without ECG changes served as control participants (negative ECG group). During a mean follow-up duration of 33.3±6.1 months, patients in the positive ECG group did not have significantly more adverse cardiac events than those in the negative ECG group. One (0.9%) patient in the negative ECG group had a nonfatal myocardial infarction (0.7% annual event rate after a negative MPI). Also in this group, two (1.8%) patients admitted with a diagnosis of CAD where they have been ruled out by angiography. A fourth case in this, in the negative ECG group, was admitted because of heart failure that proved to be secondary to a pulmonary cause and not CAD. A case only in the positive ECG group was admitted as a CAD that was ruled out by coronary angiography. Patients with normal myocardial perfusion scintigraphy in whom ST-segment depression develops during adenosine stress test appear to have no increased risk for future cardiac events compared with similar patients without ECG evidence of ischemia.

Effects of Hypercapnia on Myocardial Blood Flow in Healthy Human Subjects.

Elevation of the end-tidal partial pressure of CO2 (PETco2) increases cerebral and myocardial blood flow (MBF), suggesting that it may be a suitable alternative to pharmacologic stress or exercise for myocardial perfusion imaging. The purpose of this study was to document the pharmacodynamics of CO2 for MBF using prospective end-tidal targeting to precisely control arterial Pco2 and PET to measure the outcome variable, MBF. Methods: Ten healthy men underwent serial 82Rb PET/CT imaging. Imaging was performed at rest and during 6-min hypercapnic plateaus (baseline; PETco2 at 50, 55, and 60 mm Hg; repeat of PETco2 at 60 mm Hg; and repeat of baseline). MBF was measured using 82Rb injected 3 min after the beginning of hypercapnia and a 1-tissue-compartment model with flow-dependent extraction correction. Results were compared with those obtained during an adenosine stress test (140 μg/kg/min). Results: Baseline PETco2 was 38.9 ± 0.8 (mean ± SD) mm Hg (range, 35-43 mm Hg). All PETco2 targets were sustained, with SDs of less than 1.5 mm Hg. Heart rate, systolic blood pressure, rate × pressure product, and respiratory frequency increased with progressive hypercapnia. MBF increased significantly at each level of hypercapnia to 1.92-fold over baseline (0.86 ± 0.24 vs. 0.45 ± 0.08 mL/min/g; P = 0.002) at a PETco2 of 60 mm Hg. MBF after the administration of adenosine was significantly greater than that with the maximal hypercapnic stimulus (2.00 vs. 0.86 mL/min/g; P < 0.0001). Conclusion: To our knowledge, this study is the first to assess the response of MBF to different levels of hypercapnia in healthy humans with PET. MBF increased with increasing levels of hypercapnia; MBF at a PETco2 of 60 mm Hg was double that at baseline.

Detection of Hemodynamically Significant Coronary Artery Stenosis With CT Enhancement Ratio: A Validation Study in a Porcine Model.

Although numerous techniques that are based on CT number analysis have been proposed, the assessment of hemodynamically significant coronary artery stenosis remains a great challenge. The purpose of this study is to validate use of the CT enhancement ratio in the detection of hemodynamically significant coronary artery stenosis in a porcine model. Experiments involving eight closed-chest swine were performed. A balloon catheter was placed into the left anterior descending coronary artery to simulate different degrees of luminal stenosis. The myocardial blood flow (MBF) ratio was measured using the colored microsphere technique. The fractional flow reserve was measured using an invasive pressure wire. CT scans were performed during the first-pass phase, while the pigs were undergoing adenosine stress tests. The CT enhancement ratio and the CT attenuation ratio were calculated using data from the CT images obtained. Results suggested that the CT enhancement ratio had a strong correlation (y = 0.07245 + 0.09963x; r2 = 0.898; p < 0.001) with the MBF ratio measured using the microsphere technique, whereas only moderate correlation (y = -1.5508 + 2.2684x; r2 = 0.498; p < 0.001) was noted between the CT attenuation ratio and the MBF ratio measured using the microsphere technique. In ROC curve analysis, the AUC values of the CT enhancement ratio and the CT attenuation ratio were 0.927 and 0.829, respectively, with regard to the detection of significant ischemia during adenosine stress tests, as defined by the fractional flow reserve. The CT enhancement ratio provides a reliable prediction of the MBF ratio measured using the microsphere technique, indicating that this metric has good diagnostic performance in the detection of hemodynamically significant coronary artery stenosis. The CT enhancement ratio may have potential for use as an imaging biomarker for the relative quantitative assessment of myocardial perfusion.

Future Cardiac Events in Patients with Ischemic ECG Changes during Adenosine Infusion as a Myocardial Stress Agent and Normal Cardiac Scan

Background: We sought to determine the prognostic importance of adenosine-induced ischemic ECG changes in patients with normal SPECT myocardial perfusion images. Methods: We performed a retrospective analysis of 765 patients undergoing adenosine MPI between January 2013 and January 2015. Patients with baseline electrocardiographic (ECG) abnormalities and/or abnormal scan were excluded. Results: Overall, 67 patients (8.7%) had ischemic ECG changes during adenosine infusion in the form of ST depression of ≥1mm. Of these, 29 (43% [3.8% of all patients]) had normal MPI (positive (+) ECG group). An ageand sex-matched group of 108 patients with normal MPI without ECG changes served as control subjects (negative (-) ECG group). During a mean follow-up of 33.3 ± 6.1 months, patients in the +ECG group had no significantly more adverse cardiac events than those in the –ECG group. One (0.9%) patient within the negative ECG group had a nonfatal MI (0.7% annual event rate after a negative MPI). A case only was admitted due to heart failure in the (-) ECG group) that proved to be secondary to pulmonary cause and not of CAD. A case in this (+) ECG group admitted as a CAD that ruled out by coronary angiography. Conclusion: Patients with normal myocardial perfusion scintigraphy in whom ST-segment depression develops during adenosine stress test appear to be with no increased risk for future cardiac events compared with similar patients without ECG evidence of ischemia.