Rest Myocardial Blood Flow Research Articles

Abstract 9985: Comprehensive Cardiac Magnetic Resonance Imaging Study for Characterising Remote Myocardial Zone Contractile Function, Perfusion and Fibrosis in Type 2 Diabetes Patients with Prior Myocardial Infarction

Background: Type 2 diabetes (T2D) is associated with accelerated increased risk of myocardial infarction (MI). However, ventricular dysfunction has been identified also in T2D patients without prior MI. Objectives: Using cardiac magnetic resonance (CMR), we assessed the effect of established MI on the non-infarcted myocardium’s contractile function, rest and stress myocardial blood flow (MBF) and extra cellular volume fraction (ECV) by comparing remote zone assessments in T2D patients with prior MI (priorMI-DM) to the global assessments in T2D patients with no MI (noMI-DM) and in controls. We also aimed to extrapolate the contributions of infarct size and glycemic control (HBA1c) to cardiac functional changes (global longitudinal strain [GLS] and left ventricular ejection fraction [LVEF]) in T2D. Methods: Age and sex matched 42 priorMI-DM, 47 noMI-DM, and 22 controls underwent CMR (3T). Results: Table-1 shows clinical and CMR data. Both T2D groups showed significant reductions in LVEF and GLS. PriorMI-DM remote zone stress MBF was decreased compared to stress MBF in noMI-DM and controls (remote zone priorMI-DM 1.6±0.6ml/g/min vs global noMI-DM 1.8±0.4ml/g/min vs global control 1.9±0.4ml/g/min, p=0.01). Remote ECV and global ECV were similar in priorMI-DM and were increased compared to noMI-DM and controls. Remote ECV correlated with infarct size (r=0.66, p=0.001). In priorMI-DM, infarct size correlated with GLS (r=0.4, p=0.005) and with LVEF (r=0.2, p=0.03) but not HBA1c. In noMI-DM, there was a significant correlation between HBA1c and GLS (r=0.3, p=0.03). Conclusions: T2D patients exhibit reductions in LVEF and GLS even in the absence of prior MI, suggesting that metabolic factors beyond high prevalence of MI contribute to the cardiac dysfunction in T2D. T2D patients with prior MI show significant increases in ECV in the remote zone, accompanied by reductions in stress MBF, while remote zone contractile function remains preserved.

Coronary microvascular dysfunction is only detectable in type 2 diabetes in the presence of obesity

Abstract Background Heart failure (HF) is a leading cardiovascular complication of type 2 diabetes (T2D). Coronary microvascular dysfunction (CMD) precedes HF in diabetes and carries important prognostic information. CMD is also evident in metabolically healthy obese individuals without diabetes or hypertension. Whether diabetes causes CMD in the absence of obesity is uncertain. The interrelation among visceral adiposity and CMD has not been assessed previously. Objectives We sought to better understand the links between visceral and epicardial adipose tissue (VAT and EAT respectively) distribution, insulin resistance with myocardial perfusion, energetics and function in asymptomatic lean (LnT2D) and overweight/obese T2D patients (ObT2D) without cardiovascular disease. Methods 62 participants [27 Ob-T2D, 15 Ln-T2D, and 20 overweight controls] were recruited. Subjects underwent cardiac and abdominal magnetic resonance imaging and 31P-magnetic resonance spectroscopy, for measurements of EAT and VAT areas, rest and adenosine stress myocardial blood flow (MBF), cardiac function and phosphocreatine to ATP ratio (PCr/ATP). Fasting blood samples were taken for plasma homeostasis model assessment of insulin resistance (HOMA-IR) index calculations. Results The biochemical characteristics and multiparametric MR results are given in Table 1 and results of Pearson's regression analysis in the entire study population are given in Table 2. Stress MBF was lowest in ObT2D, while rest MBF was highest in LnT2D. Left ventricular ejection fraction (LVEF) and myocardial PCr/ATP were similarly reduced in diabetes groups. In the absence of obesity, there was no significant increase in VAT, EAT or HOMA-IR in T2D patients compared to controls. BMI and VAT, negatively correlated with LVEF, and strain parameters. PCr/ATP correlated with LVEF, but not HOMA-IR. BMI, EAT and VAT all correlated significantly with HOMA-IR, and HOMA-IR correlated with cardiac functional parameters. There was no association between HOMA-IR and myocardial perfusion. Conclusions In this study CMD was only evident in ObT2D patients, with normal rest and stress MBF in LnT2D patients. Despite normal perfusion and no significant increase in insulin resistance, LVEF and myocardial PCr/ATP were similarly reduced in LnT2D and ObT2D, and PCr/ATP correlated with LVEF. This suggests that alterations in cardiac energy metabolism are mechanistically more relevant for the pathophysiology of diabetic cardiomyopathy in LnT2D patients. In the absence of correlation between insulin resistance and myocardial perfusion, factors like inflammation and altered adipokine profile may play important roles for the pathophysiology of CMD in ObT2D patients. A better understanding of the underlying pathophysiological mechanisms of diabetic cardiomyopathy in LnT2D and ObT2D may help to develop contemporary tailored treatment and prevention strategies to tackle excess heart failure risk. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): BHFWellcome trust Table 1Table 2

No changes in myocardial perfusion following radiation therapy of left-sided breast cancer: A positron emission tomography study

BackgroundAdjuvant radiation therapy (RT) for breast cancer has improved overall survival. However, incidental exposure of the heart has been linked to development of radiation-induced heart disease. The aim of this study was, in a cohort of asymptomatic post-irradiation breast cancer patients, to investigate changes in myocardial blood flow (MBF) and presence of perfusion defects in myocardial perfusion positron-emission-tomography (PET) in the irradiated myocardium. Methods and ResultsTwenty patients treated with RT for left-sided breast cancer underwent 13N-ammonia myocardial perfusion PET 7(± 2) years after breath adapted RT to a total dose of 48 Gy given in 24 fractions. No differences in rest or stress MBF were noted between the irradiated and non-irradiated myocardium (1.29 (± 0.29) vs 1.33 (± 0.29) mL/g/min, ns; 2.74 (± 0.59) vs 2.78 (± 0.66) mL/g/min, ns, respectively). One patient demonstrated a myocardial perfusion defect localized in the irradiated anterior wall myocardium. ConclusionAlthough limited by a small sample size, early signs of cardiac injury detected by NH3 myocardial perfusion PET was at least not frequent in our cohort of patients treated with a modern RT technique for left-sided breast cancer, even 7 years after treatment. The findings however, may not rule out subsequent development of myocardial injury.

Comparison between N13NH3-PET and 99mTc-Tetrofosmin-CZT SPECT in the evaluation of absolute myocardial blood flow and flow reserve

BackgroundPET/CT is the standard for quantitative assessments of myocardial blood flow (MBF), but it requires short-lived-tracers, costly, and not widely available. SPECT with Cadmium Zinc Telluride (CZT) detectors allows dynamic acquisition and quantitation of MBF. The study aims were to compare MBF measurements by 99mTc-tetrofosmin-CZT to N13NH3 PET/CT after regadenoson-induced coronary hyperemia and to evaluate the effect of attenuation correction (AC). Methods54 patients were evaluated at rest and during vasodilation by 99mTc-tetrofosmin-CZT and N13NH3 PET/CT within 2 weeks. MBF and MBF reserve (MFR) were measured by CZT with or without AC (NAC). ResultsThe global rest MBF was 0.76 ± 0.19 mL/min/gr by PET and 0.76 ± 0.24 by AC-CZT (P = NS) and 1.14 ± 0.4 by NAC-CZT (P < 0.001 vs PET and AC-CZT). Stress MBF was higher when measured by PET than AC-CZT (1.87 ± 0.45 vs 1.62 ± 0.68 mL/min/gr, P < 0.0008), but lower than NAC-CZT (2.36 ± 1.1, P < 0.0003). The MBF reserve ratio (MFR) was higher by PET than AC-CZT (2.52 ± 0.56 vs 2.22 ± 1 (P < 0.009) and NAC-CZT (2.18 ± 1.0, P < 0.004). Linear regression was better between PET (MFR and stress MBF) and AC-CZT than between PET and NAC-CZT. ROC curve analysis showed the significant ability of AC-CZT to predict MFR < 2 and stress MBF < 1.7 (AUC = 0.75 and 0.82 respectively) and to differentiate between normal and CAD patients (AUC = 0.747 and 0.892 for MFR and stress MBF, respectively). ConclusionsOur data show a reasonable correlation between MBF and MFR measured by N13NH3-PET and 99mTc-Tetrofosmin-CZT SPECT. NAC-CZT overestimates MBF. AC is recommended when using CZT for measuring MBF.

Functional Assessment of Coronary Artery Disease by Myocardial Flow Reserve Versus Pressure-wire Based Assessment: A Systematic Review.

Positron emission tomography (PET) permits the noninvasive quantification of myocardial blood flow (MBF). Myocardial flow reserve (MFR), calculated by dividing stress MBF by rest MBF is a reliable index for the functional information of coronary artery disease. A pressure-derived physiological index, such as fractional flow reserve (FFR) is also an important measurement. Both MFR and FFR values are used to evaluate coronary physiology; however, but they are not interchangeable because each test has certain discrepancies. In this systematic review, we provide an overview of coronary physiology with PET compared to pressure-derived physiological indices.

Quantification of myocardial blood flow by CZT-SPECT with motion correction and comparison with 15O-water PET

BackgroundWe compared quantification of MBF and myocardial flow reserve (MFR) with a 99mTc-sestamibi CZT-SPECT to 15O-water PET. MethodsSPECT MBF for thirty patients in the WATERDAY study was re-analyzed by QPET software with motion correction and optimal placement of the arterial input function. 15O-water PET MBF was re-quantified using dedicated software. Inter-operator variability was assessed using repeatability coefficients (RPC). ResultsSignificant correlations were observed between global (r = 0.91, P < 0.001) and regional MBF (r = 0.86, P < 0.001) with SPECT compared to PET. Global MBF (rest 0.95 vs 1.05 ml/min/g, P = 0.07; stress 2.62 vs 2.68 mL/min/g, P = 0.17) and MFR (2.65 vs 2.75, P = 0.86) were similar between SPECT and PET. Rest (0.81 vs 0.98 mL/min/g, P = 0.03) and stress MBF (1.98 vs 2.61 mL/min/g, P = 0.01) in right coronary artery (RCA) were lower with SPECT compared to PET. However, MFR in the RCA territory was similar (2.54 vs 2.77, P = 0.21). The SPECT-PET RPC for global MBFs and MFR were 0.95 mL/min/g and 0.94, with inter-observer RPC of 0.59 mL/min/g and 0.74, respectively. ConclusionsMBF and MFR derived from CZT-SPECT with motion correction and optimal placement of the arterial input function showed good agreement with 15O-water PET, as well as low inter-operator variability.

Evaluation of visual and quantitative parameters of MPS SPECT in MINOCA patients in one year after acute coronary syndrome: comparison with CMR

Abstract Funding Acknowledgements Type of funding sources: None. Background. In recent years a group of patients with acute myocardial infarction without obstructive coronary artery disease (MINOCA) is of interest. In this group of patients, there is a lack of information related to myocardial perfusion, blood flow and reserve, which could be important in term of risk and prognosis assessment. Purpose. To assess the visual and quantitative MPS SPECT parameters in MINOCA patients compared to cardiac magnetic resonance (CMR) data. Methods. In the period from 2017 to 2018 were examined 18 (8 male, mean 62.9 ± 10.7years) consecutive patients with acute myocardial infarction without obstructive coronary artery disease (MINOCA). Within 7-10 days after admission to the hospital and one year later all patients underwent SPECT myocardial perfusion scintigraphy (MPS) with the assessment of standard indices (SSS, SRS, SDS) and quantitative parameters: rest MBF (rMBF), stress MBF (sMBF) and CFR (on CZT gamma-camera). Also, all patients underwent CMR. Based on CMR data all patient were divided into two groups: 1) patients with non-ischemic type of injury and 2) patients with ischemic type of injury. Results. We found out significant correlation between regional quantitative SPECT indices and transmural extent of myocardial infarction evaluated by CMR: r=–0.4 for sMBF; r=–0.35 for CFR (p &amp;lt; 0.05). In the first hospitalization this groups of patient didn`t have of any differences, according visual and quantitative data by SPECT. However, in one year, visual analysis showed that SSS and SDS were significantly (p &amp;lt; 0.001) lower in patient with ischemic type of injury by CMR data: 2 (2; 3) vs 5.5 (4; 9) and 2 (1; 3) vs 4.5 (2; 5), respectively. According to the quantitative MPS data analysis, global and CFR values were significantly lower in patients with non-ischemic type of injury 1.30 (1.14; 1.75) vs 1.71 (1.34; 1.81). Conclusion. The analysis of quantitative MPS SPECT parameters showed that such approach allows identifying MBF and CFR disturbances. These results showed that MINOCA patients are heterogeneous group and require more strong investigation, observation and treatment.

Myocardial perfusion after COVID-19 infection: No persisting impaired myocardial blood flow in surviving patients

Funding AcknowledgementsType of funding sources: None.Background Acute myocardial damage is common in hospitalized patients with severe COVID-19, with evidence of myocardial infarction and myocarditis demonstrated on cardiovascular magnetic resonance (CMR). Post-mortem studies have also implicated microvascular thrombosis, which may cause persistent microvascular disease. Purpose To determine the long-term coronary sequelae in recovered COVID-19 using multiparametric CMR including state-of-the-art inline quantitative stress myocardial blood flow (sMBF) mapping to assess global and regional sMBF.Methods Prospective, multicentre observational study of recovered COVID-19 patients scanned at three London CMR units. Results were compared to a propensity-matched, pre-COVID chest pain cohort (104 patients referred for perfusion CMR, with subsequently demonstrated unobstructed coronary arteries) and 27 healthy volunteers (HV). Perfusion image analysis was performed using a novel artificial intelligence approach deriving global and regional stress and rest MBF with a cut-off of >2.25mL/g/min signifying normal sMBF and <1.82mL/g/min abnormal sMBF (Kotecha JCVI 2019). Results 104 recovered, post-COVID patients (median age 62 years, 76% male; 89[87%] hospitalised, 41/89[46%] requiring ICU) underwent adenosine-stress perfusion CMR at a median 131(IQR 43-179) days from COVID-19 diagnosis. Median LVEF was 67% (IQR 60-71%; 12 (11.5%) with impaired LVEF), 51 patients (49%) had late gadolinium enhancement (LGE); 18% infarct-pattern and 33% non-ischaemic LGE. Global stress MBF in post-COVID patients was no different to age-, sex- and co-morbidities-matched controls (2.57 ± 0.77 vs. 2.40 ± 0.75 ml/g/min, p = 0.11, Figure 1), though lower than HV (3.00 ± 0.76 ml/g/min, p = 0.001). Post-COVID, multivariate predictors of low sMBF were male sex (OR 0.57, 95%CI 0.41-0.80, p = 0.001) and hypertension (OR 0.67, 95%CI 0.51-0.88, p = 0.004), but not COVID-19 disease severity (ICU admission) or presence of scar (ischemic/non-ischemic). 21/42 with reduced sMBF (<2.25mL/g/min) had regional perfusion defects consistent with epicardial coronary disease.Conclusions COVID-19 survivors do not demonstrate evidence of reduced global MBF by CMR compared to risk factor matched controls. Stress perfusion CMR identifies etiology of acute myocardial damage (infarction/myocarditis) and presence of occult coronary ischemia. Figure.

Cardiac stress T1-mapping response and extracellular volume stability of MOLLI-based T1-mapping methods

Stress and rest T1-mapping may assess for myocardial ischemia and extracellular volume (ECV). However, the stress T1 response is method-dependent, and underestimation may lead to misdiagnosis. Further, ECV quantification may be affected by time, as well as the number and dosage of gadolinium (Gd) contrast administered. We compared two commonly available T1-mapping approaches in their stress T1 response and ECV measurement stability. Healthy subjects (n = 10, 50% female, 35 ± 8 years) underwent regadenoson stress CMR (1.5 T) on two separate days. Prototype ShMOLLI 5(1)1(1)1 sequence was used to acquire consecutive mid-ventricular T1-maps at rest, stress and post-Gd contrast to track the T1 time evolution. For comparison, standard MOLLI sequences were used: MOLLI 5(3)3 Low (256 matrix) & High (192 matrix) Heart Rate (HR) to acquire rest and stress T1-maps, and MOLLI 4(1)3(1)2 Low & High HR for post-contrast T1-maps. Stress and rest myocardial blood flow (MBF) maps were acquired after IV Gd contrast (0.05 mmol/kg each). Stress T1 reactivity (delta T1) was defined as the relative percentage increase in native T1 between rest and stress. Myocardial T1 values for delta T1 (dT1) and ECV were calculated. Residuals from the identified time dependencies were used to assess intra-method variability. ShMOLLI achieved a greater stress T1 response compared to MOLLI Low and High HR (peak dT1 = 6.4 ± 1.7% vs. 4.8 ± 1.3% vs. 3.8 ± 1.0%, respectively; both p < 0.0001). ShMOLLI dT1 correlated strongly with stress MBF (r = 0.77, p < 0.001), compared to MOLLI Low HR (r = 0.65, p < 0.01) and MOLLI High HR (r = 0.43, p = 0.07). ShMOLLI ECV was more stable to gadolinium dose with less time drift (0.006–0.04% per minute) than MOLLI variants. Overall, ShMOLLI demonstrated less intra-individual variability than MOLLI variants for stress T1 and ECV quantification. Power calculations indicate up to a fourfold (stress T1) and 7.5-fold (ECV) advantage in sample-size reduction using ShMOLLI. Our results indicate that ShMOLLI correlates strongly with increased MBF during regadenoson stress and achieves a significantly higher stress T1 response, greater effect size, and greater ECV measurement stability compared with the MOLLI variants tested.

Early onset of left ventricular regional asynchrony in arteries with sub-clinical stenosis

BackgroundAsynchrony has been reported to be a marker of ischemic-induced left ventricular dysfunction, the magnitude of which correlates with extent of epicardial coronary disease. We wished to determine whether normal-appearing arterial territories with mild degrees of asynchrony have lower 82Rb PET absolute myocardial blood flow (MBF) and/or lower myocardial flow reserve (MFR). Methods and ResultsData were examined retrospectively for 105 patients evaluated for known/suspected CAD who underwent rest/regadenoson-stress 82Rb PET/CT and quantitative coronary angiography. Rest and stress absolute MBF and MFR were quantified from first-pass 82Rb PET curves. Regional relative myocardial perfusion summed stress score (SSS), summed rest score (SRS), regional phase bandwidth (BW), and regional semi-quantitative asynchrony visual scores of (Asynch) were assessed. We found that in apparently normal arteries (SSS < 4, SRS < 4 and stenosis < 70%), those with abnormally low MFR < 2.0 compared to those with MFR ≥ 2.0 had larger phase BW (186 ± 79° vs 158 ± 67°, P = .02), and more visually apparent Asynch (5.7 ± 4.2 vs 3.9 ± 3.6, P = .02), which was associated with increasing stenosis values (ρ = 0.44, P < .0001). ConclusionA subgroup of coronary territories with normal relative perfusion and normal or non-obstructive coronary disease may have reduced MFR, which is signaled physiologically by a mild degree of left ventricular asynchrony.

Influence of the arterial input sampling location on the diagnostic accuracy of cardiovascular magnetic resonance stress\xa0myocardial perfusion quantification

BackgroundQuantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) by cardiovascular magnetic resonance (CMR) perfusion requires sampling of the arterial input function (AIF). While variation in the AIF sampling location is known to impact quantification by CMR and positron emission tomography (PET) perfusion, there is no evidence to support the use of a specific location based on their diagnostic accuracy in the detection of coronary artery disease (CAD). This study aimed to evaluate the accuracy of stress MBF and MPR for different AIF sampling locations for the detection of abnormal myocardial perfusion with expert visual assessment as the reference.Methods Twenty-five patients with suspected or known CAD underwent vasodilator stress-rest perfusion with a dual-sequence technique at 3T. A low-resolution slice was acquired in 3-chamber view to allow AIF sampling at five different locations: left atrium (LA), basal left ventricle (bLV), mid left ventricle (mLV), apical left ventricle (aLV) and aortic root (AoR). MBF and MPR were estimated at the segmental level using Fermi function-constrained deconvolution. Segments were scored as having normal or abnormal perfusion by visual assessment and the diagnostic accuracy of stress MBF and MPR for each location was evaluated using receiver operating characteristic curve analysis.ResultsIn both normal (300 out of 400, 75 %) and abnormal segments, rest MBF, stress MBF and MPR were significantly different across AIF sampling locations (p < 0.001). Stress MBF for the AoR (normal: 2.42 (2.15–2.84) mL/g/min; abnormal: 1.71 (1.28–1.98) mL/g/min) had the highest diagnostic accuracy (sensitivity 80 %, specificity 85 %, area under the curve 0.90; p < 0.001 versus stress MBF for all other locations including bLV: normal: 2.78 (2.39–3.14) mL/g/min; abnormal: 2.22 (1.83–2.48) mL/g/min; sensitivity 91 %, specificity 63 %, area under the curve 0.81) and performed better than MPR for the LV locations (p < 0.01). MPR for the AoR (normal: 2.43 (1.95–3.14); abnormal: 1.58 (1.34–1.90)) was not superior to MPR for the bLV (normal: 2.59 (2.04–3.20); abnormal: 1.69 (1.36–2.14); p = 0.717).ConclusionsThe AIF sampling location has a significant impact on MBF and MPR estimates by CMR perfusion, with AoR-based stress MBF comparing favorably to that for the current clinical reference bLV.

Can deep learning identify normal coronary flow reserve from rubidium myocardial PET perfusion?

Abstract Funding Acknowledgements Type of funding sources: None. Background Impaired vasodilator function is an early manifestation of coronary artery disease (CAD) and may precede angiographic stenosis. Rest and stress myocardial blood flow (MBF) are calculated from dynamic imaging during rest/stress Rubidium (Rb) myocardial PET perfusion. Coronary flow reserve (CFR) equals stress divided by rest MBF. CFR is an independent predictor of cardiac mortality in patients with known or suspected CAD. We evaluated the prediction of CFR from analysis of stress/rest PET images by deep learning (DL) as compared with standard calculation of CFR using supervised learning applied methodology using within a commercial DL training platform. Methods 1036 patients (625 male, 411 female, mean age: 64.3 years old) were studied. Patients underwent Stress/rest Rb PET perfusion, and CFR calculated using MBF software by an expert user. Abnormal CFR was defined as &amp;lt;2.0. The left ventricle myocardium was segmented using standard software. DL was trained using polar distribution of normalized PET uptake at stress and rest, processed stress and rest images were cropped, the stress images were then subtracted from the rest images. DL was trained using 935 subtracted images and tested using the remaining 101 images. DL was trained with supervision to classify images. The image shows examples of subtracted abnormal cases (1a &amp; 1b). Results Using our supervised training methodology, the commercial MBF software platform reported 465 cases as abnormal, with 48 of these were included in the DL test set. The DL platform produced abnormal output classifiers for all the whole test set. DL accurately detected over 70% of abnormal cases. The commercial MBF software reported 571 cases as normal; with 50 of these contributing to the DL test set. DL was accurate in 48.0% of normal cases. Statistical results are shown in the table. Conclusion We have shown the proof of concept that DL algorithms trained with supervision can detect abnormal CFR. Our work shows that further work is needed to develop supervised learning methodology in order to improve accuracy for clinical use. Statistical Results Statistic Value Sensitivity 63.16% Specificity 56.67% + Predictive Value 48.00% - Predictive Value 70.83% Accuracy 59.18% Abstract Figure.

The usage CZT SPECT to assess myocardial blood flow and flow reserve in myocardial infarction with non-obstructive coronary arteries patients

Abstract Funding Acknowledgements Type of funding sources: None. Background. Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) is currently of interest in terms of a small amount of data related to myocardial perfusion, myocardial blood flow (MBF) and myocardial flow reserve (MFR). Purpose. To assess the severity of myocardial perfusion, MBF and MFR impairment in MINOCA patients in comparison to those with MI with obstructive coronary artery disease (MICAD) and non-obstructive stable coronary artery disease (SCAD). Methods. The study group comprised 40 patients (29 men, mean age 62.9 ± 10.7 years). 28 patients were admitted to the hospital due to the acute coronary syndrome. At admission all patients underwent invasive coronary angiography (ICA) and cardiac biomarkers – Creatine phosphokinase-MB (CPK-MB) and Troponin I (TnI) measurement. Two groups of patients were created based on ICA results: 1) MINOCA: with coronary artery stenosis &amp;lt;50%, n = 11; 2) MICAD: with coronary artery stenosis ≥50%, n = 17. SCAD patients group without obstructive atherosclerosis was retrospectively selected from the hospital database. All patients underwent dynamic SPECT on Cadmium-Zinc-Telluride (CZT) gamma camera with the assessment of semi-quantitative indexes of myocardial perfusion (SSS, SRS, SDS) and quantitative parameters (rest MBF (rMBF), stress MBF (sMBF) and MFR). Results. After 24 hours cardiospecific biomarkers levels in MINOCA group were significantly (p &amp;lt; 0.05) lower compared to MICAD group: CPK-MB 21.5 (13.7;45.0) vs. 94.4 (53.1;217.0) U/L; TnI 0.5 (0.1;3.3) vs. 9.8 (2.0;23.0) ng/ml. Standard myocardial perfusion indexes differed significantly (p &amp;lt; 0.05) among all three groups (except SDS between the first and second groups): MINOCA: SSS 5.0 (3.0;6.0), SDS 2.0 (1.0;3.0); MICAD: SSS 9.0 (5.0;13.0), SDS 3.0 (2,0;5.0); SCAD: SSS 1.5 (0.5;2.0), SDS 0.0 (0.0;2.0). Moreover, sMBF and MFR differed significantly in all three groups of patients: MINOCA: sMBF 1.2 (0.8;1.7) ml/min/g, MFR 2.0 (1.2;2.4); MICAD: sMBF 0.7 (0.6;1.0) ml/min/g, MFR 1.2 (1.1;1.5); control group: sMBF 2.2 (2.1;2.3) ml/min/g, MFR 2.6 (2.5;2.8). In 7/11 (64%) of MINOCA patients the value of sMBF was ≤1.5 ml/min/g. In the MICAD group 16/17 (94%) had sMBF ≤1.5 ml/min/g and all SCAD patients had sMBF &amp;gt;1.5 ml/min/g. In 4/11 (36%) of MINOCA patients MFR values were less than 2; in MICAD group MFR &amp;lt; 2 was observed in 15/17 (88%) patients. Conclusion. MINOCA patients have more severe myocardial perfusion abnormalities, lower MBF and MFR compared to those with stable CAD. It means that MINOCA patients may have other reasons for reduced myocardial blood flow, such as endothelial dysfunction, thrombophilia, etc., despite the absence of obstructive coronary artery lesion. Further studies are needed to assess added diagnostic and prognostic value of CZT SPECT derived myocardial flow indexes in MINOCA patients.

Impact of obesity on myocardial microvasculature assessed using fully-automated inline myocardial perfusion mapping CMR

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Guy"s and St Thomas" Charity University College London Hospitals Biomedical Research Centre Background Obesity and cardiovascular disease are associated, but the relationship is poorly understood. Myocardial perfusion, metabolic derangement and lipotoxicity appear adversely associated in many scenarios (myocardial injury, diastolic dysfunction, diabetes). Altered perfusion (by PET) predicts outcome, and it is hypothesised that perfusion derangement is part of causality for cardiac disease and adverse outcomes. Purpose To assess the presence and pattern of myocardial microvascular dysfunction in patients with obesity (scheduled for bariatric surgery) using stress quantitative perfusion mapping. Methods 38 subjects with obesity planned to undergo bariatric surgery and 38 age and sex matched healthy volunteers (no diabetes, no hypertension) underwent anthropometry, biochemistry and CMR at 1.5T (Siemens) with cine imaging, stress (adenosine 140-210 mcg/kg/min) and rest fully-automated quantitative perfusion mapping. Results Bariatric patients had a higher BMI (44 ± 6.4 vs 26.5 ± 4kg/m2 p = 0.001); 58%(22) were diabetic and 58%(22) had hypertension. Bariatric patients had higher absolute but lower indexed end-diastolic volumes, and overall higher ejection fractions (+5%) (see Table). Rest myocardial blood flow (MBF) in bariatric patients was the same (1.00 ± 0.3 vs 0.88 ± 0.24 p = 0.052), but stress perfusion results were significantly lower both for stress MBF (2.35 ± 0.69 vs 2.93 ± 0.76ml/g/min p = 0.001) and myocardial perfusion reserve (MPR 2.48 ± 0.82 vs 3.4 ± 0.81ml/g/min p = 0.0001). Although this was transmural, the endocardial stress MBF was particularly negatively affected in the bariatric cohort compared to controls (endocardial MBF 2.16 ± 0.65 vs 2.82 ± 0.73ml/g/min, p = 0.0001 vs epicardial MBF: 2.52 ± 0.76 vs 3.06 ± 0.79 p = 0.003), meaning there was an increased endo-epicardial stress MBF gradient in bariatric patients (0.87 ± 0.12 vs 0.92 ± 0.07 p = 0.03). Conclusion Compared to healthy controls, patients with obesity have abnormal myocardial stress perfusion with reduced global perfusion, perfusion reserve and an increased transmyocardial perfusion gradient. Table - myocardial perfusion parameters Category Bariatric patients n = 38 Controls n = 38 p value Age (years) 48 ± 11 45 ± 13 0.25 n male (%) 12 (32%) 10 (36%) 0.32 LVEDV (ml) 168 ± 37 149 ± 31 0.017 LVEDVi (ml/m2) 70.4 ± 12.3 78.8 ± 12.1 0.004 LV Mass (g) 116 ± 31 99 ± 28 0.019 EF (%) 70 ± 8 65 ± 5 0.002 LVEDV - left ventricular end-diastolic volume, EF - ejection fraction

Dynamic SPECT with assessment myocardial blood flow and coronary flow reserve in MINOCA patients: comparison with cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): grant of the President of the Russian Federation Background. In recent years a group of patients with acute myocardial infarction without obstructive coronary artery disease (MINOCA) is of interest. In this group of patients, there is a lack of information related to myocardial perfusion, blood flow and reserve, which could be important in term of risk and prognosis assessment. Purpose. To assess the global and regional myocardial blood flow and coronary flow reserve impairment in MINOCA patients compared to cardiac magnetic resonance (CMR). Methods. The study group comprised 28 patients (18 male, mean 62.9 ± 10.7years) with acute coronary syndrome. Based on ICA results all patients were divided into two groups: 1) MINOCA (n = 11); 2) patients with myocardial infarction with obstructive CAD (MICAD) (n = 17). A total of 12/17 (71%) MICAD patients underwent PCI with stenting; in 2/12 cases two arteries were revascularized. Within 7-10 days after admission to the hospital all patients underwent SPECT myocardial perfusion scintigraphy (MPS) with the assessment of standard indices (SSS, SRS, SDS) and quantitative parameters: rest MBF (rMBF), stress MBF (sMBF) and CFR (on CZT gamma-camera). Also, all patients underwent CMR with evaluation of infarct size (IF), microvascular obstruction (MVO), size of myocardial edema (ME) and transmural extent of myocardial infarction (TE). Results Visual analysis showed that SSS differed significantly (p = 0.001) among MINOCA and MICAD groups: 5 (3;6) vs 10 (5;13), respectively. According to the quantitative MPS data analysis, global sMBF and CFR values were significantly higher in MINOCA than in MICAD patients group: 1.2 (0.82;1.69) ml/min/g vs 0.62 (0.52;0.9) ml/min/g; 1.96 (1.23;2.42) vs 1.16 (0.98;1.64) , respectively. CMR indices such as IS, ME and TE were significantly lower in MINOCA compared to MICAD patients: 1.6 (0;7.8) vs 14.8 (6.3;22.6)%; 8(0;14) vs 18.5 (10;23)%; 0 (0;5) vs 18 (10;25), respectively. Seven(40%) MICAD group patients showed MVO, whereas there were no such patients in MINIOCA group. The regional analysis revealed that sMBF and CFR were significantly lower in LV regions characterized by myocardial injury compared to non-injured regions (based on CMR data): 0.78 (0.51;0.94) ml/min/g vs 1.11 (0.82;1.4) and 1.22 (0.91;1.74) vs 1.52 (1.14;2.42), respectively. Also, we found out significant correlation between regional quantitative SPECT indices and transmural extent of myocardial infarction evaluated by CMR: r=–0.4 for sMBF; r=–0.35 for CFR (p &amp;lt; 0.05). Conclusion. The analysis of quantitative MPS SPECT parameters showed that such approach allows identifying MBF and CFR disturbances both on global and regional level. These results showed that MINOCA patients characterized by mild reduction of myocardial blood flow and perfusion assessed visually and quantitatively. It means that despite the absence of obstructive coronary artery lesion this group of patients has more pronounced risk of cardiac events and need more aggressive observation and treatment.

Role of quantitative myocardial blood flow and 13N-ammonia washout for viability assessment in ischemic cardiomyopathy

ObjectivePositron emission tomography (PET) integrating assessment of perfusion with 13N-ammonia (NH3) and viability with 18F-fluorodeoxyglucose (FDG) has high accuracy to identify viable, hibernating myocardium. We tested whether quantification of myocardial blood flow (MBF) and washout (k2) can predict myocardial viability using FDG as standard of reference. MethodsIn 180 consecutive patients with ischemic cardiomyopathy, myocardium was categorized on a segment-level into normal, ischemic, hibernating, and scar. From dynamic images, stress MBF, rest MBF, and k2 were derived and myocardial flow reserve (MFR) and volume of distribution (VD) were calculated. ResultsAcross myocardial tissues, all parameters differed significantly. The area under the curve (AUC) was 0.564 (95% CI 0.527-0.601), 0.635 (0.599-0.671), 0.553 (0.516-0.591), 0.520 (0.482-0.559), and 0.560 (0.522-0.597) for stress MBF, rest MBF, MFR, k2, and VD. The generalized linear mixed model correctly classified 81% of scar as viable, hibernating myocardium. If the threshold of rest MBF to predict viability was set to 0.45 mL·min−1·g−1, sensitivity and specificity were 96% and 12%, respectively. ConclusionQuantitative NH3 PET parameters have low to moderate diagnostic performance to predict viability in ischemic cardiomyopathy. However, if rest MBF falls below 0.45 mL·min−1·g−1, viability testing by FDG-PET may be safely deferred.

Comparison of myocardial blood flow and flow reserve with dobutamine and dipyridamole stress using rubidium-82 positron emission tomography

BackgroundThe objective of this study was to compare the hyperemic myocardial blood flow (MBF) and myocardial flow reserve (MFR) obtained with dobutamine to those of dipyridamole in patients referred for myocardial perfusion imaging (MPI) using 82Rb positron emission tomography. MethodsOne hundred and fifty-six patients who underwent a 82Rb PET MPI study with dobutamine stress were included. A matching cohort of patients who underwent a 82Rb PET MPI study with dipyridamole stress was created, accounting for sex, age, history of coronary artery disease (CAD), prior revascularization, CAD risk factors, body mass index, and MPI interpretation. ResultsGlobal rest MBF (median [interquartile range] 0.84 [0.64-1.00] vs 0.69 [0.59-0.85]), stress MBF (2.36 [1.73-3.08] vs 1.66 [1.25-2.06]), MFR (2.75 [2.19-3.64] vs 2.29 [1.78-2.84]), and corrected MFR (2.85 [2.14-3.64] vs 2.20 [1.65-2.75]) were all significantly higher (P < 0.0001) in the dobutamine cohort compared to the dipyridamole cohort. ConclusionThe results of this study suggest that dobutamine produces higher MBF compared to dipyridamole in a representative population referred to nuclear cardiology laboratories.

Absolute myocardial blood flows derived by dynamic CZT scan vs invasive fractional flow reserve: Correlation and accuracy

PurposeTo define the diagnostic power of absolute myocardial blood flow (MBF) evaluation on dynamic CZT imaging in intermediate risk patients in comparison with invasive coronary angiography (ICA) and fractional flow reserve (FFR). MethodsTwenty-three stable CAD patients underwent one-day dynamic rest-stress 99mTc-Sestamibi myocardial perfusion imaging by CZT camera. Stress and rest MBF values were calculated semi-automatically using a net retention model by Leppo. Coronary flow reserve (CFR) and flow difference (FD) [MBF stress − MBF rest] were also estimated. A total of 28 vessels were functionally quantified with FFR: 19 (68%) vessels with a stenosis ≥ 70% and 9 (32%) with < 70% stenotic lesions. ResultsThe mean global MBFs at rest and during stress were 0.36 (IQR 0.33-0.54) mL/min/g and 0.67 (IQR 0.55-0.81) mL/min/g, respectively, with an average CFR of 1.80 (IQR 1.35-2.24). Moderate correlations between stenosis severity and FFR (r = 0.45; P = .01), stress MBF (r = −0.46; P = .01) and FD (r = −0.37; P = .04) were detected. FFR abnormalities were best predicted by absolute stress MBF, CFR and FD with values of ≤ 0.54 mL/min/g (sensitivity 61.5%; specificity 93.3%), ≤ 1.48 (sensitivity 69.2%; specificity 93.3%) and ≤ 0.18 mL/min/g (sensitivity 69.2%; specificity 100%), respectively. ConclusionsThe values of stress MBF, CFR and FD obtained through dynamic CZT acquisitions compare well with invasive FFR. The clinical use of dynamic acquisition of myocardial perfusion imaging by CZT may help cardiologist in the detection of hemodynamically significant CAD.

Elevated serum endothelin-1 is an independent predictor of coronary microvascular dysfunction in non-obstructive territories in patients with coronary artery disease.

Endothelin-1 contributes to the constrictor response of the coronary arteries in patients with ischemia with normal coronary arteries. There is thus increasing evidence that endothelin-1 plays a role in coronary microvascular dysfunction (CMD). We investigated whether elevated endothelin-1 is associated with CMD in patients with coronary artery disease (CAD). We prospectively studied 49 consecutive CAD patients with 1- or 2-vessel disease (age 71 ± 10 years, 43 males). Myocardial blood flow (MBF) was measured by 15O-water PET/CT at rest and during stress, and the coronary flow reserve (CFR) was calculated by dividing the stress MBF by the rest MBF. A CFR of less than 2.0 in non-obstructive regions was defined as a marker of CMD. Eighteen out of 49 (37%) CAD patients had CMD. Endothelin-1 in patients with CMD was significantly higher than in those without CMD (2.27 ± 0.81 vs. 1.64 ± 0.48pg/mL, P = 0.001). Accordingly, univariate ROC analysis showed that the continuous endothelin-1 levels significantly discriminated between the presence and absence of CMD (area under the curve = 0.746 [95%CI 0.592-0.899]). The dichotomous treatment of elevated endothelin-1 as 1.961pg/mL or more yielded the optimal discriminatory capacity, with a sensitivity of 72.2% and a specificity of 71.0%. High endothelin-1 was still a significant predictor of CMD after adjusting for diabetes mellitus (odds ratio = 6.64 [1.75-25.22], P = 0.005). Endothelin-1 is associated with CMD in non-obstructive territories in patients with CAD, suggesting that endothelin-1 is a potential target for treating CMD in CAD patients.

Coronary artery lumen volume index as a marker of flow-limiting atherosclerosis\u2014validation against 13N-ammonia positron emission tomography

ObjectivesCoronary artery volume indexed to left myocardial mass (CAVi), derived from coronary computed tomography angiography (CCTA), has been proposed as an indicator of diffuse atherosclerosis. We investigated the association of CAVi with quantitative flow parameters and its ability to predict ischemia as derived from 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI).MethodsSixty patients who underwent hybrid CCTA/PET-MPI due to suspected CAD were retrospectively included. CAVi was defined as total coronary artery lumen volume over myocardial mass, both derived from CCTA. From PET-MPI, quantitative stress and rest myocardial blood flow (MBF) and myocardial flow reserve (MFR) were obtained and correlated with CAVi, and semi-quantitative perfusion images were analyzed for the presence of ischemia. Harrell’s c-statistic and net reclassification improvement (NRI) analysis were performed to evaluate the incremental value of CAVi over the CCTA model (i.e., stenosis > 50% and > 70%).ResultsCAVi correlated moderately with stress MBF and MFR (R = 0.50, p < 0.001, and R = 0.39, p = 0.002). Mean stress MBF and MFR were lower in patients with low (i.e., ≤ 20.2 mm3/g, n = 24) versus high (i.e., > 20.2 mm3/g, n = 36) CAVi (p < 0.001 for both comparisons). CAVi was independently associated with abnormal stress MBF (OR 0.90, 95% CI 0.82–0.998, p = 0.045). CAVi increased the predictive ability of the CCTA model for abnormal stress MBF and ischemia (c-statistic 0.763 versus 0.596, pdiff < 0.05 and 0.770 versus 0.645, pdiff < 0.05, NRI 0.84, p = 0.001 and 0.96, p < 0.001, respectively).ConclusionsCAVi exhibits incremental value to predict both abnormal stress MBF and ischemia over CCTA alone.Key Points• Coronary artery volume indexed to left myocardial mass (CAVi), derived from coronary computed tomography angiography (CCTA), is correlated with myocardial blood flow indices derived from13N-ammonia positron emission tomography myocardial perfusion imaging.• CAVi is independently associated with abnormal stress myocardial blood flow.• CAVi provides incremental diagnostic value over CCTA for both abnormal stress MBF and ischemia.