Normal values of myocardial blood flow measured with dynamic myocardial computed tomography perfusion.

AIMS: Dynamic myocardial computed tomography (CT) perfusion (DM-CTP) can, in combination with coronary CT angiography (CCTA), provide anatomical and functional evaluation of coronary artery disease (CAD). However, normal values of myocardial blood flow (MBF) are needed to identify impaired myocardial blood supply in patients with suspected CAD. We aimed to establish normal values for MBF measured using DM-CTP, to assess the effects of age and sex, and to assess regional distribution of MBF. METHODS AND RESULTS: A total of 82 healthy individuals (46 women) aged 45-78 years with normal coronary arteries by CCTA underwent either rest and adenosine stress DM-CTP (n = 30) or adenosine-induced stress DM-CTP only (n = 52). Global and segmental MBF were assessed. Global MBF at rest and during stress were 0.93 ± 0.42 and 3.58 ± 1.14 mL/min/g, respectively. MBF was not different between the sexes (P = 0.88 at rest and P = 0.61 during stress), and no correlation was observed between MBF and age (P = 0.08 at rest and P = 0.82 during stress). Among the 16 myocardial segments, significant intersegmental differences were found (P < 0.01), which was not related to age, sex, or coronary dominance. CONCLUSION: MBF assessed by DM-CTP in healthy individuals with normal coronary arteries displays significant intersegmental heterogeneity which does not seem to be affected by age, sex, or coronary dominance. Normal values of MBF may be helpful in the clinical evaluation of suspected myocardial ischaemia using DM-CTP.

Association between contrast-enhanced adenosine-stress perfusion cardiac magnetic resonance imaging and invasive coronary angiogram for the detection of coronary artery disease: A retrospective analysis.

Objective: The objective of this study was to determine the diagnostic value of stress perfusion CMR for the detection of coronary artery disease. Methods: The was a retrospective cross sectional study in which 43 subjects were included from Cardiac MRI unit in the Hayatabad Medical Complex, Peshawar for study from 1st April 2020 to 30th November 2020. All the subjects who had been referred for stress perfusion CMR with suspected CAD were included in the study. Cardiac MRI both at rest and with adenosine stress perfusion was performed which was followed by invasive coronary angiography. Result: A total of 43 patients were enrolled for the detection or exclusion CAD who underwent stress perfusion CMRI and invasive coronary artery angiography. The study revealed strong and statistically significant association between positive stress perfusion CMR and positive coronary angiogram vs negative stress perfusion CMR and negative coronary angiogram (p= value 0.0001). Conclusions: Stress perfusion CMRI can be considered as a first line, relatively safe, noninvasive test with significant accuracy to diagnose coronary artery disease in patients with suspected CAD without subjecting these patients to invasive coronary angiogram.

The value of myocardial work in the estimation of left ventricular systolic function in patients with coronary microvascular disease: A study based on adenosine stress echocardiography.

Background: Coronary microvascular dysfunction (CMD) is associated with increased cardiovascular events in patients with angina with non-obstructive coronary (ANOCA), especially heart failure. Conventional echocardiography is difficult to identify early alterations in cardiac function due to CMD. Methods: We recruited 78 ANOCA patients. All patients underwent conventional echocardiography examination, adenosine stress echocardiography and examination of coronary flow reserve (CFR) by transthoracic echocardiography. Based on the CFR results, patients were divided into the CMD group (CFR < 2.5) and the non-CMD group (CFVR ≥ 2.5). Demographic data, conventional echocardiographic parameters, two-dimensional speckle-tracking echocardiography (2D-STE) parameters and myocardial work (MW) were compared between the two groups at rest and at stress. Logistic regression was used to analyze the factors associated with CMD. Results: There was no significant difference in conventional echocardiography parameters, 2D-STE related indices or MW at rest between the two groups. Global work index (GWI), global contractive work (GCW), and global work efficiency (GWE) were lower in the CMD group than in the non-CMD group at stress (p = 0.040, 0.044, <0.001, respectively), but global waste work (GWW) and peak strain dispersion (PSD) were higher (both p < 0.001). GWI and GCW were associated with systolic blood pressure, diastolic blood pressure, product of heart rate and blood pressure, GLS and coronary flow velocity. While GWW was mainly correlated with PSD, GWE was correlated with PSD and GLS. In the non-CMD group, the responses to adenosine was mainly manifested as an increase in GWI, GCW and GWE (p = 0.001, 0.001, 0.009, respectively) and a decrease in PSD and GWW (p = 0.001, 0.015, respectively). In the CMD group, the response to adenosine was mainly manifested as an increase in GWW and a decrease in GWE (p = 0.002, and 0.006, respectively). In the multivariate regression analysis, we found that ΔGWW (difference in GWW before vs. after adenosine stress) and ΔPSD (difference in PSD before vs. after adenosine stress) were independent factors associated with CMD. The ROC curves showed that the composite prediction model consisting of ΔGWW and ΔPSD had excellent diagnostic value for CMD (area under the curve = 0.913). Conclusion: In the present study, we found that CMD caused deterioration of myocardial work in ANOCA patients under adenosine stress, and that increased cardiac contraction asynchrony and wasted work may be the main changes caused by CMD.

Evaluation of left ventricular function in ischemia with non-obstructive coronary arteries: a research based on adenosine stress myocardial contrast echocardiography.

Patients with ischemia with non-obstructive coronary arteries (INOCA) have an increased risk of adverse cardiovascular events in the future, which is widespread but underdiagnosed. The purpose of this study is to explore the application value of adenosine stress myocardial contrast echocardiography (ASMCE) in INOCA disease, so that clinicians can early identify and intervene patients with left ventricular function subclinical impairment in INOCA. We enrolled 118 patients with INOCA by ASMCE and invasive coronary angiography (ICA), 97 of whom had complete data. The study population was divided into two subgroups depending on coronary flow velocity reserve (CFVR): impaired CFVR group (n = 34) and normal CFVR group (n = 63). Global longitudinal strain endocardial myocardial (GLSendo), mid-myocardial (GLSmid) and epicardial myocardial (GLSepi) increased after stress in both groups; transmural strain, wall motion scored index (WMSI) and myocardial perfusion scored index (MPSI) increased and FORCE decreased in impaired CFVR group after stress, but there was no difference in normal group before and after stress. There was no significant difference in left ventricular myocardial mechanical parameters, including ΔGLSendo, ΔGLSmid, ΔGLSepi, GLSendo-epi Reserve, Δpeak strain dispersion (PSD), PSD Reserve between the two groups, but ΔEF, strain reserve and left ventricular contractile reserve (LVCR) in the impaired CFVR group were lower than those in the normal CFVR group, while ΔWMSI and ΔMPSI were increased. CFVR can be a clinically valuable indicator in the ASMCE diagnosis of patients with microvascular angina pectoris in INOCA. In the evaluation of left ventricular function in INOCA patients, attention should be paid not only to myocardial deformation, but also to the dynamic changes of LVCR and myocardial perfusion during peak hyperemia.

Adenosine stress myocardial contrast echocardiography evaluates myocardial perfusion abnormalities in patients with hypertrophic cardiomyopathy / 中华超声影像学杂志

Objective:To detect the abnormal changes of myocardial blood perfusion in patients with hypertrophic cardiomyopathy(HCM) by myocardial contrast echocardiography (MCE) combined with adenosine stress test.Methods:Fifteen adult patients with HCM who were treated in Fuwai Central China Cardiovascular Hospital from May 2021 to March 2022 were prospectively selected as the HCM group, and eighteen healthy volunteers matched by gender, age and body surface area during the same period were chosen as the control group. All subjects underwent routine echocardiography, rest and adenosine stress MCE. The MCE images were analyzed by QLab software to obtain the myocardial perfusion parameters: peak signal intensity (A value), rising slope of the curve (β value) and A×β value, and the differences of above parameters between the two groups were compared.According to whether the end-diastolic wall thickness ≥12 mm, the myocardial segments in the HCM group were divided into hypertrophic segments and non-hypertrophic segments. The differences in myocardial perfusion parameters were compared among control group segments, hypertrophic segments and non-hypertrophic segments of the HCM group. The correlations of stress myocardial blood flow with maximal left ventricular wall thickness (MLVWT), left ventricular mass index (LVMI) and left atrial volume index (LAVI) in the HCM group were analyzed.Results:Compared with the control group, the A value, β value and A×β value of whole myocardium, hypertrophic segments and non-hypertrophic segments in the HCM group were significantly decreased in the rest and adenosine stress state, and the differences were statistically significant (all P<0.05). In the stress state, the A value, β value and A×β value of the hypertrophic segments were significantly lower than those in the non-hypertrophic segments in the HCM group, and the detection rate of abnormal perfusion segments in the HCM group was significantly higher than that in the rest state(all P<0.05). Compared with the control group, the myocardial blood flow reserve of whole myocardium, hypertrophic segments and non-hypertrophic segments in the HCM group were significantly decreased, and the differences were statistically significant(all P<0.05). The stress myocardial blood flow in the HCM group was negatively correlated with MLVWT, LVMI and LAVI ( r=-0.815, -0.805, -0.742; all P<0.05). Conclusions:Myocardial blood perfusion abnormalities can occur in both hypertrophic and non-hypertrophic myocardial segments in patients with HCM, and adenosine stress MCE can significantly improve the sensitivity of detecting myocardial perfusion abnormalities. The stress myocardial blood flow in patients with HCM is negatively correlated with MLVWT, LVMI and LAVI.

Myocardial blood flow is the dominant factor influencing cardiac magnetic resonance adenosine stress T2.

Stress imaging identifies ischemic myocardium by comparing hemodynamics during rest and hyperemic stress. Hyperemia affects multiple hemodynamic parameters in myocardium, including myocardial blood flow (MBF), myocardial blood volume (MBV), and venous blood oxygen levels (PvO2 ). Cardiac T2 is sensitive to these changes and therefore is a promising non-contrast option for stress imaging; however, the impact of individual hemodynamic factors on T2 is poorly understood, making the connection from altered T2 to changes within the tissue difficult. To better understand this interplay, we performed T2 mapping and measured various hemodynamic factors independently in healthy pigs at multiple levels of hyperemic stress, induced by different doses of adenosine (0.14-0.56 mg/kg/min). T1 mapping quantified changes in MBV. MBF was assessed with microspheres, and oxygen consumption was determined by the rate pressure product (RPP). Simulations were also run to better characterize individual contributions to T2. Myocardial T2, MBF, oxygen consumption, and MBV all changed to varying extents between each level of adenosine stress (T2 = 37.6-41.8 ms; MBF = 0.48-1.32 mL/min/g; RPP = 6507-4001 bmp*mmHg; maximum percent change in MBV = 1.31%). Multivariable analyses revealed MBF as the dominant influence on T2 during hyperemia (significant ß-values >7). Myocardial oxygen consumption had almost no effect on T2 (ß-values <0.002); since PvO2 is influenced by both oxygen consumption and MBF, PvO2 changes detected by T2 during adenosine stress can be attributed to MBF. Simulations varying PvO2 and MBV confirmed that PvO2 had the strongest influence on T2, but MBV became important at high PvO2 . Together, these data suggest a model where, during adenosine stress, myocardial T2 responds predominantly to changes in MBF, but at high hyperemia MBV is also influential. Thus, changes in adenosine stress T2 can now be interpreted in terms of the physiological changes that led to it, enabling T2 mapping to become a viable non-contrast option to detect ischemic myocardial tissue.

The association between heart rate reserve and impaired coronary flow velocity reserve: a study based on adenosine stress echocardiography.

This study was to explore the correlation between heart rate reserve (HRR) to coronary flow velocity reserve (CFVR), using adenosine stress echocardiography (SE), in patients with angina and no obstructive coronary artery disease (ANOCA). 111 ANOCA patients underwent adenosine SE were enrolled, which were divided into two groups, impaired CFVR group (CFVR < 2) and control groups (CFVR ≥ 2). The relationships between HRR and impaired CFVR were explored in total and subgroup to sex. A reduced HRR during adenosine infusion was seen in ANOCA patients with impaired CFVR (25.73 ± 8.39 vs. 34.30 ± 19.93, P < 0.001). Compared to respective controls, the blunted HRR to adenosine was more pronounced in female patients (women: 27.21 ± 8.01 vs. 39.48 ± 10.57, P < 0.001; men: 24.05 ± 8.70 vs. 29.12 ± 8.69, P = 0.041). A strong association between CFVR and a blunted HRR was observed in women (r = 0.46, P < 0.001), while no association in men (r = 0.18, P = 0.199). In female, a multivariate logistic regression identified HRR as the strongest negative predictor of impaired CFVR [HR (95% CI) = 0.854 (0.764-0.956), P = 0.006]. Based on the ROC curve, HRR < 35% was a strong indicator of impaired CFVR, with AUC of 0.838, sensitivity of 70%, and specificity of 87% in females. A blunted HRR was seen in patients with impaired CFVR, with a most pronounced effect being seen in female patients. The blunted HRR < 35% is intricately linked to impaired CFVR in women with ANOCA beyond the value of traditional risk factors, which could ultimately contribute to risk stratification of impaired CFVR in such patients.

A comparison of standard and high dose adenosine protocols in routine vasodilator stress cardiovascular magnetic resonance: dosage affects hyperaemic myocardial blood flow in patients with severe left ventricular systolic impairment.

BACKGROUND: Adenosine stress perfusion cardiovascular magnetic resonance (CMR) is commonly used in the assessment of patients with suspected ischaemia. Accepted protocols recommend administration of adenosine at a dose of 140 µg/kg/min increased up to 210 µg/kg/min if required. Conventionally, adequate stress has been assessed using change in heart rate, however, recent studies have suggested that these peripheral measurements may not reflect hyperaemia and can be blunted, in particular, in patients with heart failure. This study looked to compare stress myocardial blood flow (MBF) and haemodynamic response with different dosing regimens of adenosine during stress perfusion CMR in patients and healthy controls. METHODS: 20 healthy adult subjects were recruited as controls to compare 3 adenosine perfusion protocols: standard dose (140 µg/kg/min for 4 min), high dose (210 µg/kg/min for 4 min) and long dose (140 µg/kg/min for 8 min). 60 patients with either known or suspected coronary artery disease (CAD) or with heart failure and different degrees of left ventricular (LV) dysfunction underwent adenosine stress with standard and high dose adenosine within the same scan. All studies were carried out on a 3 T CMR scanner. Quantitative global myocardial perfusion and haemodynamic response were compared between doses. RESULTS: In healthy controls, no significant difference was seen in stress MBF between the 3 protocols. In patients with known or suspected CAD, and those with heart failure and mild systolic impairment (LV ejection fraction (LVEF) ≥ 40%) no significant difference was seen in stress MBF between standard and high dose adenosine. In those with LVEF < 40%, there was a significantly higher stress MBF following high dose adenosine compared to standard dose (1.33 ± 0.46 vs 1.10 ± 0.47 ml/g/min, p = 0.004). Non-responders to standard dose adenosine (defined by an increase in heart rate (HR) < 10 bpm) had a significantly higher stress HR following high dose (75 ± 12 vs 70 ± 14 bpm, p = 0.034), but showed no significant difference in stress MBF. CONCLUSIONS: Increasing adenosine dose from 140 to 210 µg/kg/min leads to increased stress MBF in patients with significantly impaired LV systolic function. Adenosine dose in clinical perfusion assessment may need to be increased in these patients.

Feasibility and Utility of Adenosine Stress Echocardiography in Children Following Post-Arterial Switch Operation: A Comparison with Technetium 99m-Sestamibi Myocardial Perfusion SPECT (MPS).

There is a need for a sensitive, safe, and cost-effective tool for coronary assessment among asymptomatic post-operative children who have undergone arterial switch operation (ASO) for transposition of great arteries (TGA). Adenosine stress echocardiography may be useful in assessing major structures as well for coronary functional assessment. Twenty-six children [median age 6.0 years; IQR 4.9-7.1 years, (22 boys)], who had undergone ASO at a median age of 40 days (IQR 30-75 days), were prospectively included. Left ventricular ejection fraction (LVEF) was calculated in both rest and stress studies (140 µg/kg/min of adenosine IV over 4 min), along with assessment of regional myocardial wall motion. Coronary flow reserve (CFR) was also measured in the left anterior descending artery (LAD). Technetium 99m-MIBI [0.2mCi/kg] was injected after 2 min of adenosine infusion. Adenosine infusion had to be stopped in two children, due to transient atrioventricular (AV) block. The LVEF increased from 55.87 ± 7.27 to 61.20 ± 7.70% (p < 0.001) with adenosine stress. No significant regional wall motion abnormality was seen in rest or stress. Distal LAD could not be visualized in four patients. Basal and peak coronary flow velocities were 41.51 ± 14.12 and 74.18 ± 6.01 cm/s. Mean CFR was 1.91 ± 0.51. Myocardial perfusion scintigraphy (MPS) was normal in all the patients. Four patients were lost to follow-up and remaining children did not develop any adverse events in the follow-up period of 64.5 ± 7.19 months. Adenosine stress echocardiography is feasible as the initial screening test in the assessment of asymptomatic post-operative children with ASO, at minimal to no inconvenience to the patient. The findings concurred with stress MPS.

Assessment of Multivessel Coronary Artery Disease Using Cardiovascular Magnetic Resonance Pixelwise Quantitative Perfusion Mapping.

OBJECTIVES: The authors sought to compare the diagnostic accuracy of quantitative perfusion maps to visual assessment (VA) of first-pass perfusion images for the detection of multivessel coronary artery disease (MVCAD). BACKGROUND: VA of first-pass stress perfusion cardiac magnetic resonance (CMR) may underestimate ischemia in MVCAD. Pixelwise perfusion mapping allows quantitative measurement of regional myocardial blood flow, which may improve ischemia detection in MVCAD. METHODS: One hundred fifty-one subjects recruited at 2 centers underwent stress perfusion CMR with myocardial perfusion mapping, and invasive coronary angiography with coronary physiology assessment. Ischemic burden was assessed by VA of first-pass images and by quantitative measurement of stress myocardial blood flow using perfusion maps. RESULTS: In patients with MVCAD (2-vessel [2VD] or 3-vessel disease [3VD]; n = 95), perfusion mapping identified significantly more segments with perfusion defects (median segments per patient 12 [interquartile range (IQR): 9 to 16] by mapping vs. 8 [IQR: 5 to 9.5] by VA; p < 0.001). Ischemic burden (IB) measured using mapping was higher in MVCAD compared with IB measured using VA (3VD mapping 100 % (75% to 100%) vs. first-pass 56% (38% to 81%) ; 2VD mapping 63% (50% to 75%) vs. first-pass 41% (31% to 50%); both p < 0.001), but there was no difference in single-vessel disease (mapping 25% (13% to 44%) vs. 25% (13% to 31%). Perfusion mapping was superior to VA for the correct identification of extent of coronary disease (78% vs. 58%; p < 0.001) due to better identification of 3VD (87% vs. 40%) and 2VD (71% vs. 48%). CONCLUSIONS: VA of first-pass stress perfusion underestimates ischemic burden in MVCAD. Pixelwise quantitative perfusion mapping increases the accuracy of CMR in correctly identifying extent of coronary disease. This has important implications for assessment of ischemia and therapeutic decision-making.

Splenic Switch-Off for Determining the Optimal Dosage for Adenosine Stress Cardiac MR in Terms of Stress Effectiveness and Patient Safety.

BACKGROUND: Adenosine stress MRI is well established for the evaluation of known and suspected coronary artery disease. However, a proportion of patients might be "under-stressed" using the standard adenosine dose. PURPOSE: To compare three different adenosine dosages for stress MRI in terms of stress adequacy based on splenic switch-off (SSO) and limiting side effects. STUDY TYPE: Prospective. POPULATION: In all, 100 patients were randomized in group 1 (33 pts), group 2 (34 pts), and group 3 (33 pts), receiving dosages of 140 µg/kg/min, 175 µg/kg/min, or 210 µg/kg/min, respectively. SSO was evaluated visually and quantitatively. SEQUENCE: Stress perfusion was performed using a 1.5T scanner in three short axes using a standard single-shot, saturation recovery gradient-echo sequence. ASSESSMENT: Three blinded experienced operators evaluated SSO on stress and rest perfusion acquisitions in the three groups. The signal intensity of the spleen and myocardium and the presence of inducible ischemia and late gadolinium enhancement were assessed. STATISTICAL ANALYSIS: T-test, analysis of variance (ANOVA), chi-squared test, and Pearson's correlation coefficient. RESULTS: SSO was present more frequently in patients receiving 175 µg/kg/min and 210 µg/kg/min (31/33 [94%] and 27/29 [93%], respectively) compared to those receiving the standard dose (19/33 [58%], P < 0.05). A positive stress result was noted in 3/33 (9%) patients receiving 140 µg/kg/min vs. 9/33 (27%) patients receiving 175 µg/kg/min and 10/31 (33%) patients receiving 210 µg/kg/min (P < 0.05 for all, P < 0.05 for group 1 vs. groups 2, 3). The relative decrease of splenic signal intensity at hyperemia vs. baseline was significantly lower in group 1 compared to groups 2 and 3 (-33% vs. -54%, -56%, respectively; P < 0.05). No adverse events during scanning were noted in groups 1 and 2, whereas in group 3 four examinations were stopped due to severe dyspnea (n = 2) and AV-blockage (n = 2). DATA CONCLUSION: A dosage of 175 µg/kg/min adenosine results in a higher proportion of SSO, which may be an indirect marker of adequate coronary vasodilatation and simultaneously offers similar safety compared to the standard 140 µg/kg/min dosage. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2 J. MAGN. RESON. IMAGING 2020;52:1732-1742.

Comparison of MOLLI and ShMOLLI in Terms of T1 Reactivity and the Relationship between T1 Reactivity and Conventional Signs of Response during Adenosine Stress Perfusion CMR

Background: One of the most important techniques of cardiac magnetic resonance in assessment of coronary heart diseases is adenosine stress myocardial first-pass perfusion imaging. Using this imaging method, there should be an adequate response to the drug adenosine to make an accurate evaluation. The conventional signs of drug response are not always observed and are often subjective. Methods based on splenic perfusion might possess limitations as well. Therefore, T1 mapping presents as a novel, quantitative and reliable method. There are several studies analyzing this newly discovered property of different T1 mapping sequences. However most of these studies are enrolling only one of the techniques. Aims: To compare modified look-locker inversion recovery and shortened modified look-locker inversion recovery sequences in terms of T1 reactivity and to determine the relationship between T1 reactivity and conventional stress adequacy assessment methods in adenosine stress perfusion cardiac magnetic resonance. Study Design: A cross-sectional study using STARD reporting guideline. Methods: Thirty-four consecutive patients, who were referred for adenosine stress perfusion cardiac magnetic resonance with suspect of myocardial ischemia, were prospectively enrolled into the study. Four patients were disqualified, and thirty patients were included in the final analysis. Using both modified look-locker inversion recovery and shortened modified look-locker inversion recovery, midventricular short axis slices of T1 maps were acquired at rest and during peak adenosine stress before gadolinium administration. Then, they were divided into six segments according to the 17-segment model proposed by the American Heart Association, and separate measurements were made from each segment. Mean rest and mean stress T1 values of remote, ischemic, and infarcted myocardium were calculated individually per subject. During adenosine administration, patients' heart rates and blood pressures are measured and recorded every one minute. Adenosine stress perfusion images were examined for the presence of splenic switch-off. Results: There was a significant difference between rest and stress T1 values of remote myocardium in both modified look-locker inversion recovery and shortened modified look-locker inversion recovery (p<0.001). In both modified look-locker inversion recovery and shortened modified look-locker inversion recovery there was no significant correlation between T1 reactivity and heart rates response (modified look-locker inversion recovery p=0.30, shortened modified look-locker inversion recovery p=0.10), blood pressures response (modified look-locker inversion recovery p=0.062, shortened modified look-locker inversion recovery p=0.078), splenic perfusion (modified look-locker inversion recovery p=0.35, shortened modified look-locker inversion recovery p=0.053). There was no statistically significant difference between modified look-locker inversion recovery and shortened modified look-locker inversion recovery regarding T1 reactivity of remote (p=0.330), ischemic (p=0.068), and infarcted (p=0.116) myocardium. Conclusion: T1 reactivity is independent of the other stress response signs and modified look-locker inversion recovery and shortened modified look-locker inversion recovery do not differ in terms of T1 reactivity.

Detection of Functionally Significant Coronary Artery Disease: Role of Regional Post Systolic Shortening.

BACKGROUND: The main goal of this manuscript was to evaluate the diagnostic value of the global and regional postsystolic shortening (PSS) parameters, assessed by two-dimensional (2D) speckle-tracking echocardiography, at rest and during dobutamine stress for the detection of functionally significant coronary artery stenoses in patients with moderate pretest probability of stable coronary artery disease (CAD). METHODS: Dobutamine stress echocardiography (DSE) and adenosine stress myocardial perfusion imaging by cardiac magnetic resonance (CMR-MPI) were performed on 83 patients with moderate pretest probability of stable CAD and left ventricle ejection fraction ≥55%. CAD was defined as ≥50% diameter stenoses on invasive coronary artery angiography (CAA) validated as hemodynamically significant by CMR-MPI. According to invasive CAA and CMR-MPI results, patients were divided into two groups: Nonpathologic CAD (-) group: 38 (45.8%) and pathologic CAD (+) group: 45 (54.2%). RESULTS: There were no significant differences in clinical characteristics, conventional 2D echocardiography between the two groups at rest and during low dobutamine dose. Regional postsystolic index (PSI) during recovery phase had the highest area under the receiver operating characteristic curve (AUC) (AUC 0.882, sensitivity 87%, specificity 92%) for the detection of functionally significant one-vessel disease. During high dobutamine dose, regional PSI had sensitivity 78% and specificity 81% (AUC 0.78) to detect significant CAD. Regional PSI remained the same tendency remains for the detection of multiple-vessel CAD. Other myocardial deformation parameters were less sensitive and specific during high dobutamine dose and recovery phase. CONCLUSIONS: PSS parameters showed to be sensitive and specific in detecting hemodynamically significant coronary artery stenosis in patients with stable CAD with moderate pretest probability. The study revealed that the assessment of regional PSI performed during recovery improves the diagnostic accuracy of DSE for the detection of functionally significant CAD.

Effect of ursodeoxycholic acid in facilitating early hepatic clearance of radiotracer among patients undergoing 99mTc-sestamibi myocardial perfusion scintigraphy: A randomized double blind placebo controlled parallel trial.

BACKGROUND: Infra-cardiac tracer activity due to persistent hepatic activity interferes in inferior and infero-septal wall assessment during 99mTc-MIBI SPECT/CT myocardial perfusion scintigraphy (MPS) in evaluation of patients with coronary artery disease. It affects image interpretation with increased study duration. Ursodeoxycholic acid (UDCA) is known to enhance hepatic excretion of bilirubin and bile salts, though its role in enhancing the hepatic tracer clearance in facilitating cardiac imaging is not known. METHODS: This prospective, randomized double-blind, placebo controlled clinical trial of 120 patients, referred for adenosine stress or viability MPS studies were randomized 1:1 to receive either UDCA or placebo. Outcome was quantitative & qualitative improvement in imaging for better interpretation and to reduce the waiting time for scan. RESULTS: 118 participants (59 ± 11.9 years; 84 men) underwent adenosine stress MPS or viability MPS. Sixty participants had UDCA while 58 had placebo intervention. The study showed significant decrease in liver counts with improved myocardial to liver ratio at 30 and 60 minutes in adenosine stress MPS group, and marginally significant alteration in liver counts at 60 minutes in viability MPS group receiving UDCA, resulting in better images. CONCLUSION: UDCA intervention in MPS provides early and better image due to faster hepatic tracer clearance.

Adenosine stress perfusion cardiac magnetic resonance imaging in patients undergoing intracoronary bone marrow cell transfer after ST-elevation myocardial infarction: the BOOST-2 perfusion substudy.

AIMS: In the placebo-controlled, double-blind BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) 2 trial, intracoronary autologous bone marrow cell (BMC) transfer did not improve recovery of left ventricular ejection fraction (LVEF) at 6 months in patients with ST-elevation myocardial infarction (STEMI) and moderately reduced LVEF. Regional myocardial perfusion as determined by adenosine stress perfusion cardiac magnetic resonance imaging (S-CMR) may be more sensitive than global LVEF in detecting BMC treatment effects. Here, we sought to evaluate (i) the changes of myocardial perfusion in the infarct area over time (ii) the effects of BMC therapy on infarct perfusion, and (iii) the relation of infarct perfusion to LVEF recovery at 6 months. METHODS AND RESULTS: In 51 patients from BOOST-2 (placebo, n = 10; BMC, n = 41), S-CMR was performed 5.1 ± 2.9 days after PCI (before placebo/BMC treatment) and after 6 months. Infarct perfusion improved from baseline to 6 months in the overall patient cohort as reflected by the semi-quantitative parameters, perfusion defect-infarct size ratio (change from 0.54 ± 0.20 to 0.43 ± 0.22; P = 0.006) and perfusion defect-upslope ratio (0.54 ± 0.23 to 0.68 ± 0.22; P < 0.001), irrespective of randomised treatment. Perfusion defect-upslope ratio at baseline correlated with LVEF recovery (r = 0.62; P < 0.001) after 6 months, with a threshold of 0.54 providing the best sensitivity (79%) and specificity (74%) (area under the curve, 0.79; 95% confidence interval, 0.67-0.92). CONCLUSION: Infarct perfusion improves from baseline to 6 months and predicts LVEF recovery in STEMI patients undergoing early PCI. Intracoronary BMC therapy did not enhance infarct perfusion in the BOOST-2 trial.

Impact of baseline calibration on semiquantitative assessment of myocardial perfusion reserve by adenosine stress MRI.

In this study, we sought to investigate the impact of baseline calibration, which is used in quantitative cardiac MRI perfusion analysis to correct for surface coil inhomogeneity and noise, on myocardial perfusion reserve index (MPRI) and its contribution to previously reported paradoxical low MPRI < 1.0 in patients with unobstructed coronary arteries. Semiquantitative perfusion analysis was performed in 20 patients with unobstructed coronary arteries undergoing stress/rest perfusion CMR and in ten patients undergoing paired rest perfusion CMR. The following baseline calibration settings were compared: (1) baseline division, (2) baseline subtraction and (3) no baseline calibration. In uncalibrated analysis, we observed ~ 20% segmental dispersion of signal intensity (SI)-over-time curves. Both baseline subtraction and baseline division reduced relative dispersion of t0-SI (p < 0.001), but only baseline division corrected for dispersion of peak-SI and maximum upslope also (p < 0.001). In the assessment of perfusion indices, however, baseline division resulted in paradoxical low MPRI (1.01 ± 0.23 vs. 1.63 ± 0.38, p < 0.001) and rest perfusion index (RPI 0.54 ± 0.07 vs. 0.94 ± 0.12, p < 0.001), respectively. This was due to a reversed ratio of blood-pool and myocardial baseline-SI before the second perfusion study caused by circulating contrast agent from the first injection. In conclusion, baseline division reliably corrects for inhomogeneity of the surface coil sensitivity profile facilitating comparisons of regional myocardial perfusion during hyperemia or at rest. However, in the assessment of MPRI, baseline division can lead to paradoxical low results (even MPRI < 1.0 in patients with unobstructed coronary arteries) potentially mimicking severely impaired perfusion reserve. Thus, in the assessment of MPRI we propose to waive baseline calibration.

Combined single-session cardiovascular magnetic resonance: stress perfusion and three-dimensional pulmonary vein angiography for stratification of atrial fibrillation patients with chest pain syndromes prior to catheter ablation.

AIMS: To determine the clinical utility of a combined single-session cardiovascular magnetic resonance (CMR) imaging protocol integrating adenosine stress perfusion and three-dimensional pulmonary vein angiography for stratification of atrial fibrillation (AF) patients referred for pulmonary vein isolation (PVI) and complaining about chest pain syndromes. METHODS AND RESULTS: The preprocedural CMR examination (adenosine stress perfusion, late gadolinium enhancement, and three-dimensional pulmonary vein angiography) was performed in 357 consecutive AF patients with chest pain syndromes referred for PVI. Stress perfusion results were used for stratification: ischaemia positive patients underwent invasive coronary angiography, ischaemia negative patients underwent PVI, and follow-up/outcome data were collected (combined primary endpoint of cardiac death/non-fatal myocardial infarction). The integrated CMR protocol had a high success rate (356/357, 99.7%), a short total examination duration (<30 min in all patients), and delivered high-quality three-dimensional pulmonary vein angiography in all patients undergoing PVI (324/324, 100%). Variants of pulmonary vein anatomy were identified in 33% of all patients (117/357). Stress positivity (28/356, 8%) had a high positive predictive value for identification of obstructive coronary artery disease (86%), while stress negativity carried a low short-term event rate following PVI (cumulative 1-year event-free survival rate, 99.6%). CONCLUSION: Combined single-session CMR as a routine diagnostic workup for AF patients with chest pain syndromes prior to PVI proved to represent a time-efficient and effective stratification tool.

Impact of caffeine on myocardial perfusion reserve assessed by semiquantitative adenosine stress perfusion cardiovascular magnetic resonance.

BACKGROUND: Adenosine is used in stress perfusion cardiac imaging to reveal myocardial ischemia by its vasodilator effects. Caffeine is a competitive antagonist of adenosine. However, previous studies reported inconsistent results about the influence of caffeine on adenosine's vasodilator effect. This study assessed the impact of caffeine on the myocardial perfusion reserve index (MPRI) using adenosine stress cardiovascular magnetic resonance imaging (CMR). Moreover, we sought to evaluate if the splenic switch-off sign might be indicative of prior caffeine consumption. METHODS: Semiquantitative perfusion analysis was performed in 25 patients who underwent: 1) caffeine-naïve adenosine stress CMR demonstrating myocardial ischemia and, 2) repeat adenosine stress CMR after intake of caffeine. MPRI (global; remote and ischemic segments), and splenic perfusion ratio (SPR) were assessed and compared between both exams. RESULTS: Global MPRI after caffeine was lower vs. caffeine-naïve conditions (1.09 ± 0.19 vs. 1.24 ± 0.19; p <  0.01). MPRI in remote myocardium decreased by caffeine (1.24 ± 0.19 vs. 1.49 ± 0.19; p <  0.001) whereas MPRI in ischemic segments (0.89 ± 0.18 vs. 0.95 ± 0.23; p = 0.23) was similar, resulting in a lower MPRI ratio (=remote/ischemic segments) after caffeine consumption vs. caffeine-naïve conditions (1.41 ± 0.19 vs. 1.64 ± 0.35, p = 0.01). The SPR was unaffected by caffeine (SPR 0.38 ± 0.19 vs. 0.38 ± 0.18; p = 0.92). CONCLUSION: Caffeine consumption prior to adenosine stress CMR results in a lower global MPRI, which is driven by the decreased MPRI in remote myocardium and underlines the need of abstinence from caffeine. The splenic switch-off sign is not affected by prior caffeine intake.

Haemodynamic effects of pharmacologic stress with adenosine in patients with left ventricular systolic dysfunction.

BACKGROUND: In patients with heart failure, downregulation of adenosine receptor gene expression and impaired adenosine-related signal transduction may result in a diminished response to adenosine. This may have implications for cardiac stress testing. We evaluated the haemodynamic response to intravenous adenosine in patients with left ventricular systolic dysfunction (LVSD) undergoing stress cardiovascular magnetic resonance imaging (CMR). METHODS AND RESULTS: We retrospectively examined 497 consecutive patients referred for clinical stress CMR. Blood pressure and heart rate responses with intravenous adenosine were compared in patients with normal, mild-moderately impaired and severely impaired LV systolic function (ejection fraction [EF] > 55%, 36-55% and < 35%, respectively). Following 2 min of adenosine infusion, there was a significant difference between the groups in the heart rate change from baseline, with a diminished heart rate response in patients with LVSD (p < 0.001). An increase in the dose of adenosine (up to 210 µg/kg/min) was required to achieve a sufficient haemodynamic response in more patients with severe LVSD (41%) than those with mild-moderately impaired and normal LV systolic function (24% and 19%, respectively, p < 0.001). Even with increased doses of adenosine in subjects with severe LVSD, peak haemodynamic response remained blunted. With multivariate analysis age (p < 0.001) and LVEF (p = 0.031) were independent predictors of heart rate response to adenosine. CONCLUSION: Patients with reduced LVEF referred for stress CMR may have a blunted heart rate response to adenosine. Further study is warranted to determine whether this may be associated with reduced diagnostic accuracy and also the potential utility of further dose increases or alternative stressors.

Gadolinium-Free Cardiac MR Stress T1-Mapping to Distinguish Epicardial From Microvascular Coronary Disease.

BACKGROUND: Novel cardiac magnetic resonance (CMR) stress T1 mapping can detect ischemia and myocardial blood volume changes without contrast agents and may be a more comprehensive ischemia biomarker than myocardial blood flow. OBJECTIVES: This study describes the performance of the first prospective validation of stress T1 mapping against invasive coronary measurements for detecting obstructive epicardial coronary artery disease (CAD), defined by fractional flow reserve (FFR <0.8), and coronary microvascular dysfunction, defined by FFR ≥0.8 and the index of microcirculatory resistance (IMR ≥25 U), compared with first-pass perfusion imaging. METHODS: Ninety subjects (60 patients with angina; 30 healthy control subjects) underwent CMR (1.5- and 3-T) to assess left ventricular function (cine), ischemia (adenosine stress/rest T1 mapping and perfusion), and infarction (late gadolinium enhancement). FFR and IMR were assessed ≤7 days post-CMR. Stress and rest images were analyzed blinded to other information. RESULTS: Normal myocardial T1 reactivity (ΔT1) was 6.2 ± 0.4% (1.5-T) and 6.2 ± 1.3% (3-T). Ischemic viable myocardium downstream of obstructive CAD showed near-abolished T1 reactivity (ΔT1 = 0.7 ± 0.7%). Myocardium downstream of nonobstructive coronary arteries with microvascular dysfunction showed less-blunted T1 reactivity (ΔT1 = 3.0 ± 0.9%). Stress T1 mapping significantly outperformed gadolinium-based first-pass perfusion, including absolute quantification of myocardial blood flow, for detecting obstructive CAD (area under the receiver-operating characteristic curve: 0.97 ± 0.02 vs. 0.91 ± 0.03, respectively; p < 0.001). A ΔT1 of 1.5% accurately detected obstructive CAD (sensitivity: 93%; specificity: 95%; p < 0.001), whereas a less-blunted ΔT1 of 4.0% accurately detected microvascular dysfunction (area under the receiver-operating characteristic curve: 0.95 ± 0.03; sensitivity: 94%; specificity: 94%: p < 0.001). CONCLUSIONS: CMR stress T1 mapping accurately detected and differentiated between obstructive epicardial CAD and microvascular dysfunction, without contrast agents or radiation.