Regional Myocardial Flow Research Articles

Regional vs. Global Myocardial Flow Reserve Discordance in CZT SPECT: Implications for Risk Stratification

Regional vs. Global Myocardial Flow Reserve Discordance in CZT SPECT: Implications for Risk Stratification

CZT SPECT regional myocardial flow reserve: can it enhance risk stratification?

CZT SPECT regional myocardial flow reserve: can it enhance risk stratification?

Myocardial perfusion and flow reserve in the asynchronous heart: mechanistic insight from a computational model.

The tight coupling between myocardial oxygen demand and supply has been recognized for decades, but it remains controversial whether this coupling persists under asynchronous activation, such as during left bundle branch block (LBBB). Furthermore, it is unclear whether the amount of local cardiac wall growth, following longer lasting asynchronous activation, can explain differences in myocardial perfusion distribution between subjects. For better understanding of these matters, we built upon our existing modeling framework for cardiac mechanics-to-perfusion coupling by incorporating coronary autoregulation. Regional coronary flow was regulated with a vasodilator signal based on regional demand, as estimated from regional fiber stress-strain area. Volume of left ventricular wall segments was adapted with chronic asynchronous activation towards a homogeneous distribution of myocardial oxygen demand per tissue weight. Modeling results show that: (1) both myocardial oxygen demand and supply are decreased in early-activated regions and increased in late-activated regions; (2) but that regional hyperemic flow remains unaffected; while (3) regional myocardial flow reserve (the ratio of hyperemic to resting myocardial flow) decreases with increases in absolute regional myocardial oxygen demand as well as with decreases in wall thickness. These findings suggest that septal hypoperfusion in LBBB represents an autoregulatory response to reduced myocardial oxygen demand. Furthermore, oxygen demand-driven remodeling of wall mass can explain asymmetric hypertrophy and the related homogenization of myocardial perfusion and flow reserve. Finally, the inconsistent observations of myocardial perfusion distribution can primarily be explained by the degree of dyssynchrony, the degree of asymmetric hypertrophy, as well as the imaging modality used.

Diagnostic value of regional myocardial flow reserve measurements using Rubidium-82 PET

PurposeVisual assessment of Rubidium (Rb-82) PET myocardial perfusion images is usually combined with global myocardial flow reserve (MFR) measurements. However, small regional blood flow deficits may go unnoticed. Our aim was to compare the diagnostic value of regional with global MFR in the detection of obstructive coronary artery disease (oCAD).MethodsWe retrospectively included 1519 patients referred for rest and regadenoson-induced stress Rb-82 PET/CT without prior history of oCAD. MFR was determined globally, per vessel territory and per myocardial segment and compared using receiver-operating characteristic analysis. Vessel MFR was defined as the lowest MFR of the coronary territories and segmental MFR as the lowest MFR of the 17-segments. The primary endpoint was oCAD on invasive coronary angiography.ResultsThe 148 patients classified as having oCAD had a lower global MFR (median 1.9, interquartile range [1.5–2.4] vs. 2.4 [2.0–2.9]), lower vessel MFR (1.6 [1.2–2.1] vs. 2.2 [1.9–2.6]) and lower segmental MFR (1.3 [ 0.9–1.6] vs. 1.8 [1.5–2.2]) as compared to the non-oCAD patients (p < 0.001). The area under the curve for segmental MFR (0.81) was larger (p ≤ 0.005) than of global MFR (0.74) and vessel MFR (0.78).ConclusionsThe use of regional MFR instead of global MFR is recommended as it improves the diagnostic value of Rb-82 PET in the detection of oCAD.

Quantitative myocardial perfusion 82Rb-PET assessed by hybrid PET/coronary-CT: Normal values and diagnostic performance

PurposeWe aimed to assess normal values for quantified myocardial blood flow (MBF) on a hybrid PET/coronary-CT scanner and to test their diagnostic performance in patients with suspected CAD. Materials and MethodsPatients underwent 82Rb-PET/CT and integrated CT-based coronary angiography (CCTA) and were classified as normal (no stenosis), with non-obstructive stenosis (< 50%) and with CAD (≥ 50%). Global and regional stress MBF (sMBF), rest MBF and myocardial flow reserve (MFR) were calculated. Ischemia was defined as SDS ≥ 2, severe ischemia as SDS ≥ 7. Results357 consecutive patients were included. Global sMBF and MFR were higher in normal patients than in patients with CAD (3.61 ± 0.71 vs 3.04 ± 0.77, P < 0.0001; 3.08 ± 0.84 vs 2.68 ± 0.79, P = 0.0001), but not different compared to patients with non-obstructive stenosis (3.61 ± 0.71 vs 3.43 ± 0.69, P = 0.052; 3.08 ± 0.84 vs 2.99 ± 0.82, P = 0.45). sMBF yielded superior accuracy over MFR in identifying both ischemia (AUC 0.74 vs 0.62, P = 0.003) and severe ischemia (AUC 0.88 vs 0.78, P = 0.012). Optimal threshold for global sMBF to rule out myocardial ischemia was 3.5 mL g−1 min−1. ConclusionsNormal quantitative values are provided. Global sMBF provided higher diagnostic accuracy than MFR. Using sMBF-threshold of 3.5 mL·g−1·min−1 on 82Rb-PET/CT yielded similar NPV (96%) as CCTA to rule out CAD. Hence, resting scan could be omitted in patients with sMBF values above reference.

13N-ammonia PET-derived right ventricular longitudinal strain and myocardial flow reserve in right coronary artery disease.

We developed a feature-tracking algorithm for use with electrocardiography-gated high-resolution 13N-ammonia positron emission tomography (PET) imaging, and we hypothesized it could be used to clarify the association between right ventricular (RV) longitudinal strain (LS) and right coronary artery (RCA) ischemia. The aim of this study was to investigate the association between the reduction of regional myocardial flow reserve (MFR) in RCA territories and PET-derived LS of the RV free wall. Ninety-three patients with coronary artery stenosis > 50%, diagnosed by coronary computed tomography angiography, and 10 controls were retrospectively analyzed. RV-LS in the free wall was measured by a feature-tracking technique on the resting and stressed 13N-ammonia PET images of horizontal long axis slices. The patients were sub-grouped according to regional MFR values at the territories of RCA, left anterior descending artery (LAD), and left circumflex coronary artery (LCx): RCA-MFR < 2.0 [n = 34], RCA-MFR ≥ 2.0 but MFR < 2.0 at LAD or LCx territories [n = 11], and MFR ≥ 2.0 for all territories [n = 48]. Stress and resting RV-LS were compared in each of the four groups. Multiple comparisons of RV-LS among the four groups were performed in the stress and resting state. Decreased stress RV-LS in patients with an RCA-MFR < 2.0 was observed. In the patients with MFR ≥ 2.0 for all territories, the stressed RV-LS was significantly increased compared to that in the resting state. Significantly decreased RV free wall LS during adenosine stress in patients with RCA-MFR < 2.0 was observed in the other three groups. We measured RV myocardial LS using feature tracking in cine imaging of 13N-ammonia PET. The results of this study suggest that PET-derived stressed RV-LS is useful for detecting reduced RV myocardial motion due to ischemia in the RCA territory.

Value of regional myocardial flow measurements using Rubidium-82 PET

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The combination of myocardial blood flow (MBF) measurements using Rubidium-82 (Rb-82) PET and visual assessment of the PET images is increasingly used due to its high diagnostic and prognostic value. Typically, flow measurements are calculated and used for the myocardium as a whole (global). However, small regional flow deficits may go unnoticed when only looking at global flow values. Purpose To compare the diagnostic value of regional and global myocardial flow measurements using Rb-82 PET in the detection of obstructive CAD. Methods We retrospectively included 1034 patients with no history of coronary artery disease (CAD) referred for rest and regadenoson-induced stress Rb-82 PET/CT. MBFs were calculated using Lortie’s one-tissue compartment model. Myocardial flow reserve (MFR) was calculated as the ratio of MBF during stress and rest. Regional flow was determined per vessel and per segment. Vessel MFR was defined as the lowest flow reserve of LAD, LCX and RCA territories and segmental MFR as the lowest flow reserve in all 17 segments. Follow-up data were obtained from medical records. Patients were classified to have obstructive CAD if follow-up included a positive invasive coronary angiography (ICA), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or all cause death. Receiver-operating characteristic (ROC) analyses were constructed to compare the diagnostic value of global and regional flow values. Results Follow-up was obtained in all 1034 patients and the median follow-up time was 2.1 years. Myocardial flow reserve values were significantly lower (p &amp;lt; 0.001) in the 128 patients classified with obstructive CAD than in the 906 patients without obstructive CAD: global MFR (median 1.9 [interquartile range 1.6-2.4] vs. 2.5 [2.1-2.9]); vessel MFR (1.6 [1.3-2.1] vs. 2.3 [1.9-2.6]); Segmental MFR (1.3 [0.9-1.7] vs. 1.9 [1.6-2.2]). The area under the curve of vessel MFR (0.79 ± 0.02) and segmental MFR (0.81 ± 0.02) were similar but significantly (p &amp;lt; 0.001) larger than the area of global MFR (0.75 ± 0.03), as shown in the Figure. Conclusion The diagnostic value improved with the use of regional MFR instead of global MFR measurements in the detection of obstructive CAD. Therefore, it seems that visual assessment of PET images can best be combined with regional flow measurements either on a per vessel or a per segment basis in Rubidium-82 PET myocardial perfusion imaging.

Prognostic value of regional myocardial flow reserve derived from 13N-ammonia positron emission tomography in patients with suspected coronary artery disease

PurposeTo assess the prognostic value of regional quantitative myocardial flow measures as assessed by 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI) in patients with suspected coronary artery disease (CAD).MethodsWe retrospectively included 150 consecutive patients with suspected CAD who underwent clinically indicated 13 N-ammonia PET-MPI and who did not undergo revascularization within 90 days of PET-MPI. The presence or absence of a decreased global myocardial flow reserve (i.e., MFR < 2) as well as decreased regional MFR (i.e., ≥ 2 adjacent segments with MFR < 2) was recorded, and patients were classified as having preserved global and regional MFR (MFR group 1), preserved global but decreased regional MFR (MFR group 2), or decreased global and regional MFR (MFR group 3). We obtained follow-up regarding major adverse cardiac events (MACE, i.e., a combined endpoint including all-cause death, non-fatal myocardial infarction, and late revascularization) and all-cause death.ResultsOver a median follow-up of 50 months (IQR 38–103), 30 events occurred in 29 patients. Kaplan–Meier analysis showed significantly reduced event-free and overall survival in MFR groups 2 and 3 compared to MFR group 1 (log-rank: p = 0.015 and p = 0.013). In a multivariable Cox regression analysis, decreased regional MFR was an independent predictor for MACE (adjusted HR 3.44, 95% CI 1.17–10.11, p = 0.024) and all-cause death (adjusted HR 4.72, 95% CI 1.07–20.7, p = 0.04).ConclusionsA decreased regional MFR as assessed by 13 N-ammonia PET-MPI confers prognostic value by identifying patients at increased risk for future adverse cardiac outcomes and all-cause death.

Use of strain, strain rate, tissue velocity imaging, and endothelial function for early detection of cardiovascular involvement in young diabetics

Background:Subtle structural and functional changes may precede the onset of overt global left ventricular (LV) dysfunction. Data pertaining to tissue velocity imaging (TVI)and strain imaging to assess regional myocardial function and flow mediated vasodilatation are limited in young patients with diabetes.Materials:Conventional echocardiography, TVI parameters along with strain (S), and strain rate (SR) were measured in 50 young diabetics (15.16 ± 2.95 years, mean HBA1c 8.15 ± 1.37 g %) and 25 controls (15.60 ± 2.51 years). Flow-mediated dilation (FMD), nitrate--mediated dilatation (NMD), and carotid intima–media thickness were also assessed.Results:Conventional echocardiography parameters were similar in patients and controls; however, deceleration time of the mitral inflow velocity (early deceleration time) was significantly shorter in patients when compared with controls (149.06 ± 31.66 vs. 184.56 ± 19.27 ms, P =0.001). Patients had lower strain values at the basal lateral LV (21.39 ± 4.12 vs. 23.78 ± 2.02; P =0.001), mid-lateral LV (21.43 ± 4.27 vs. 23.17 ± 1.92 P =0.02), basal septum (20.59 ± 5.28 vs. 22.91 ± 2.00; P = 0.01), and midseptum (22.06 ± 4.75 vs. 24.10 ± 1.99; P = 0.01) as compared to controls. SR at the basal and midsegments of the lateral LV wall and at the basal septum was also significantly lower in diabetic patients. Diabetic children also had endothelial dysfunction with significantly lower FMD (8.36 ± 4.27 vs. 10.57 ± 4.12, P = 0.04).Conclusions:LV strain indices and flow--mediated dilatation are impaired in asymptomatic children and adolescents with type 1 diabetes mellitus despite absence of overt heart failure and normal ejection fraction. Early detection of subclinical regional myocardial dysfunction by deformation analysis including strain and strain rate may be useful in the asymptomatic diabetic population.

Regional myocardial strain analysis via 2D speckle tracking echocardiography: validation with sonomicrometry and correlation with regional blood flow in the presence of graded coronary stenoses and dobutamine stress

BackgroundQuantitative regional strain analysis by speckle tracking echocardiography (STE) may be particularly useful in the assessment of myocardial ischemia and viability, although reliable measurement of regional strain remains challenging, especially in the circumferential and radial directions. We present an acute canine model that integrates a complex sonomicrometer array with microsphere blood flow measurements to evaluate regional myocardial strain and flow in the setting of graded coronary stenoses and dobutamine stress. We apply this unique model to rigorously evaluate a commercial 2D STE software package and explore fundamental regional myocardial flow-function relationships.MethodsSonomicrometers (16 crystals) were implanted in epicardial and endocardial pairs across the anterior myocardium of anesthetized open chest dogs (n = 7) to form three adjacent cubes representing the ischemic, border, and remote regions, as defined by their relative locations to a hydraulic occluder on the mid-left anterior descending coronary artery (LAD). Additional cardiac (n = 3) and extra-cardiac (n = 3) reference crystals were placed to define the cardiac axes and aid image registration. 2D short axis echocardiograms, sonometric data, and microsphere blood flow data were acquired at baseline and in the presence of mild and moderate LAD stenoses, both before and during low-dose dobutamine stress (5 μg/kg/min). Regional end-systolic 2D STE radial and circumferential strains were calculated with commercial software (EchoInsight) and compared to those determined by sonomicrometry and to microsphere blood flow measurements. Post-systolic indices (PSIs) were also calculated for radial and circumferential strains.ResultsLow-dose dobutamine augmented both strain and flow in the presence of mild and moderate stenoses. Regional 2D STE strains correlated moderately with strains assessed by sonomicrometry (Rradial = 0.56, p < 0.0001; Rcirc = 0.55, p < 0.0001) and with regional flow quantities (Rradial = 0.61, Rcirc = 0.63). Overall, correspondence between 2D STE and sonomicrometry was better in the circumferential direction (Bias ± 1.96 SD: − 1.0 ± 8.2% strain, p = 0.06) than the radial direction (5.7 ± 18.3%, p < 0.0001). Mean PSI values were greatest in low flow conditions and normalized with low-dose dobutamine.Conclusions2D STE identifies changes in regional end-systolic circumferential and radial strain produced by mild and moderate coronary stenoses and low-dose dobutamine stress. Regional 2D STE end-systolic strain measurements correlate modestly with regional sonomicrometer strain and microsphere flow measurements.

P314 The functional effects of intramural course of coronary arteries by two-dimensional speckle-tracking dobutamine stress

Abstract Background Intramural course of a coronary artery is a common anatomic variant, especially in the left anterior descending coronary artery (LAD). However, its effect on the myocardial function during stress remains still unclear. Purpose We compared regional myocardial strain measured by speckle tracking during dobutamine stress echocardiography (DSE) in patients with or without intramural course of the LAD. Methods Fifty patients (63 ±7 years) were prospectively enrolled and underwent DSE, computed tomography angiography (CTA), quantitative 15-Oxygen water positron emission tomographic perfusion imaging (PET), and invasive angiography. Patients with superficial (&amp;gt;1 mm) or deep (&amp;gt;2 mm) intramural course in the LAD were identified using CTA. Regional longitudinal strain and strain rate (LS, LSr), circumferential strain and strain rate (CS, CSr), as well as radial strain and strain rate (RS, RSr) were measured at rest, at a dobutamine dose of 20 mg/kg/min, at peak stress, and at early recovery (1 min after stress). Obstructive coronary artery disease (CAD) was defined as &amp;gt;75% stenosis or 40% to 75% stenosis combined with either fractional flow reserve &amp;lt; 0.80 or ischemia on PET. Results Intramural course of the LAD was detected in 17 patients. Of these, 8 patients had obstructive CAD and were excluded. Thus, 9 patients with intramural course and 11 controls without intramural course or obstructive CAD in the LAD were included. Myocardial strain and strain rate in the myocardial territory distal to intramural segment were similar to those in controls at rest, dobutamine stress and early recovery (Figure). Furthermore, there were no significant differences, at all time points, between the regional strain values of the myocardial segments those distal to the superficial and deep intramural course. In the myocardium distal to an intramural coronary segment, regional myocardial flow measured by PET during adenosine stress correlated with the regional LS (r = 0.80, p = 0.004), LSr (r = 0.66, p = 0.03), and CS (r = 0.69, p = 0.02) and RS (r = 0.53, p = 0.07) at the peak dobutamine stress. However, there was no correlation between flow and strain at rest. Conclusions Myocardial strain is not consistently affected in patients with intramural course of the LAD during dobutamine stress as assessed by speckle tracking echocardiography. Larger studies are warranted to evaluate whether certain anatomical variants cause abnormalities in systolic myocardial strain. Abstract P314 Figure.

P1496Use of strain, strain rate, tissue velocity imaging and endothelial function for early detection of cardiovascular involvement in young diabetics

Abstract Background Subtle structural and functional changes may precede the onset of overt global left ventricular dysfunction and obvious reduction of ejection fraction (EF), especially in young diabetics. Data pertaining to tissue velocity indices (TVI) and strain imaging to assess regional myocardial function and flow mediated vasodilatation is limited in young patients with diabetes. Purpose To evaluate conventional echocardiography parameters, tissue doppler indices, global and regional strain, carotid intimal medial thickness (CIMT), endothelial dependent (FMD) and independent function (NMD) of brachial artery in young patients (age &lt;18 years) with type 1 diabetes and compare them with matched controls. Methods Conventional echocardiography parameters, tissue velocity indices (TVI) parameters along with strain (S), and strain rate (SR) in basal and mid left ventricular (LV) lateral wall, right ventricular (RV) lateral wall and septum were measured in 50 young diabetics (age 15.16±2.95 years, mean HBA1c 8.15±1.37 gm %) and 25 controls (age 15.60±2.51 years). Flow-mediated dilatation (FMD), nitrate mediated dilatation and carotid intimal media thickness (CIMT) were also estimated. Results Conventional echocardiography parameters were similar in patients and controls however deceleration time of the mitral inflow velocity (EDT) was significantly shorter in patients when compared with controls (149.06±31.66 vs. 184.56±19.27 ms, p&lt;0.05). Lateral early diastolic myocardial velocity (LV-Em) was significantly lower (10.30±0.99 vs. 11.67±3.21, p&lt;0.05) whereas lateral late diastolic myocardial velocity (LV-Am) was significantly higher than controls (11.73±1.44 vs. 8.82±1.69, p&lt;0.05), thus a significantly lower ratio of early/late diastolic velocity at the basal segment of lateral LV (LV-Em/Am). Lower strain values at the basal lateral LV (21.39±4.12 vs. 23.78±2.02; p&lt;0.05), mid lateral LV (21.43±4.27 vs. 23.17±1.92; p&lt;0.05), basal septum (20.59±5.28 vs. 22.91±2.00; p&lt;0.05), and mid septum (22.06±4.75 vs. 24.10±1.99; p&lt;0.05) as compared to controls. SR at the basal and mid segments of the lateral LV wall and at the basal septum were also significantly lower in diabetic subjects. Strain rate (SR) in mid septal, basal and mid RV were lower than controls although not statistically significant. Patients also had significantly lower flow mediated dilatation (FMD) (8.36±4.27 vs. 10.57±4.12, p&lt;0.05) implying endothelial dysfunction. Strain rate in diabetic patient Conclusion Left ventricular strain indices are impaired in asymptomatic children and adolescents with type 1 DM despite absence of overt heart failure and normal ejection fraction. Early detection of subclinical regional myocardial dysfunction by deformation analysis including strain and strain rate may be useful in the asymptomatic diabetic population. In addition, evidence of endothelial dysfunction in the form of impaired flow mediated vasodilatation was observed in the diabetic children. Acknowledgement/Funding None

P2702Assessment of endothelial shear stress and functional significance of coronary lesions by computed tomography coronary angiography (CTCA) and computational fluid dynamics: a comparison with PET

Abstract Background The feasibility of assessing endothelial shear stress (ESS) in coronary lesions by non-invasive imaging and its potential role in different clinical settings has been recently explored. However, the relationship of ESS with functional indices derived by computed tomography coronary angiography (CTCA) and its value in predicting perfusion changes by quantitative positron emission tomography (PET) downstream stenotic vessels has not been assessed. Purpose To investigate the feasibility of calculating local ESS, its relationship with stenosis severity as well as with virtual functional assessment index (vFAI), and the comparative performance of the two parameters for predicting impaired coronary vasodilating capability in terms both of stress myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients submitted to CTCA. Methods Thirty-two patients (23 male-9 female, mean age 65.6±7.2 years) with intermediate pre-test likelihood of coronary artery disease (CAD), who were enrolled in the EVINCI and SMARTool projects, and had undergone CTCA with vFAI and PET myocardial perfusion imaging with 15 O-water or 13 N-ammonia were included in the study. PET was considered positive when &gt;1 contiguous segments showed both stress MBF ≤2.3 mL/g/min and MFR ≤2.5 for 15 O-water or ≤1.79 mL/g/min and ≤2.0, for 13 N-ammonia respectively. A vFAI threshold of 0.85 was used as predictor of impaired vasodilating capability. ESS computation was based on a mean aortic pressure of 100 mmHg for the inlet and a mean blood flow at rest of 0.00105 kg/s for the outlet. ESS was calculated (Pa) in the full length of the stenosis and the mean value was obtained. Results Hybrid imaging analysis was performed in CTCA and PET datasets. 51 coronary segments were assessed. There were 27 lesions with stenosis 31–50% and 24 lesions with stenosis 51–70%. ESS was higher in the latter (20.4, IQ: 11.4–32.1 vs. 10.4, IQ: 5.5–15.7, p=0.04). Similarly, ESS was higher in stenoses with impaired vasodilating capacity compared to those without, although this difference did not reach statistical significance (22.8, IQ: 13.2–35.1 vs. 10.6, IQ: 5.7–22.1, p=0.10). The ROC curve analysis for prediction of both abnormal stress MBF and MFR followed the same pattern (AUC=0.668, 95% confidence interval (CI): 0.490–0.810, p=0.11).On the other hand, there was a moderate negative correlation (r=−0.41, p=0.004) between ESS and vFAI and the former was lower in stenoses with vFAI &gt;0.85 compared to those below this threshold (7.35, IQ: 3.2–13.9 vs. 19.1, IQ: 14.1–32.8, p=0.012). vFAI was a good predictor of coronary flow capacity (AUC=0.737, CI: 0.58–0.85, p=0.02). Conclusion Calculation of ESS is feasible in CTCA datasets. ESS was related with stenosis severity and there was a trend to be higher in lesions with impaired coronary vasodilating capability. ESS is modestly related with vFAI and may also be an additional predictor of impaired regional myocardial flow obtained by PET imaging. Acknowledgement/Funding This study has received funding from the EU H2020 research and innovation programme under grant agreement No 689068 and from p-Med GR 5002802

P158Prognostic value of regional myocardial flow reserve derived from 13N-ammonia myocardial perfusion positron emission tomography in patients without known coronary artery disease

P158Prognostic value of regional myocardial flow reserve derived from 13N-ammonia myocardial perfusion positron emission tomography in patients without known coronary artery disease

Qualitative assessments of myocardial ischemia by cardiac MRI and coronary stenosis by invasive coronary angiography in relation to quantitative perfusion by positron emission tomography in patients with known or suspected stable coronary artery disease

BackgroundTo relate findings of qualitative evaluation of first-pass perfusion-CMR and anatomical evaluation on coronary angiography (CA) to the reference standard of quantitative perfusion, cardiac PET, in patients with suspected or known stable coronary artery disease (CAD). Methods and ResultsForty-one patients referred for CA due to suspected stable CAD, prospectively performed adenosine stress/rest first-pass perfusion-CMR as well as 13N-NH3 PET on the same day, 4 ± 3 weeks before CA. Angiographers were blinded to PET and CMR results. Regional myocardial flow reserve (MFR) < 2.0 on PET was considered pathological. Vessel territories with stress-induced ischemia by CMR or vessels with stenosis needing revascularization had a significantly lower MFR compared to those with no regional stress-induced ischemia or vessels not needing revascularization (P < 0.001). In 4 of 123 vessel territories with stress-induced ischemia by CMR, PET showed a normal MFR. In addition, 12 of 123 vessels that underwent intervention showed normal MFR assessed by PET. ConclusionThe limited performance of qualitative assessment of presence of stable CAD with CMR and CA, when related to quantitative 13N-NH3 cardiac PET, shows the need for fully quantitative assessment of myocardial perfusion and the use of invasive flow reserve measurements for CA, to confirm the need of elective revascularization.

RELATIONSHIP BETWEEN GLOBAL MYOCARDIAL BLOOD FLOW EVALUATED BY PHASE CONTRAST CINE-MAGNETIC RESONANCE IMAGING AND REGIONAL PRESSURE WIRE-DERIVED PHYSIOLOGICAL INDICES

Recent studies proposed the integral of absolute regional peak stress myocardial flow and coronary flow reserve (CFR) for the assessment of ischemia and coronary physiology. However, few studies have documented the relationship between global absolute myocardial blood flow (MBF) and the regional

Myocardial Uptake of 7′-(Z)-[ 123 I]Iodorotenone During Vasodilator Stress in Dogs With Critical Coronary Stenoses

There is a well-recognized need for a new generation of single photon emission computed tomography (SPECT) perfusion tracers with improved myocardial extraction over a wide flow range. Radiotracers that target complex I of the mitochondrial electron transport chain have been proposed as a new class of myocardial perfusion imaging agents. 7-(Z)-[(125)I]iodorotenone ((125)I-ZIROT) has demonstrated superior myocardial extraction and retention characteristics in rats and in isolated perfused rabbit hearts. We sought to fully characterize the biodistribution and myocardial extraction versus flow relationship of (123)I-ZIROT in an intact large-animal model. The (123)I-ZIROT was administered during adenosine A(2A) agonist-induced hyperemia in 5 anesthetized dogs with critical left anterior descending (LAD) stenoses. When left circumflex (LCx) flow was maximal, (123)I-ZIROT and microspheres were coinjected and the dogs were euthanized 5 minutes later. (123)I-ZIROT biodistribution was evaluated in 2 additional dogs by in vivo planar imaging. At (123)I-ZIROT injection, transmural LAD flow was unchanged from baseline (mean±SEM, 0.90±0.22 versus 0.87±0.11 mL/[min · g]; P=0.92), whereas LCx zone flow increased significantly (mean±SEM, 3.25±0.51 versus 1.00±0.17 mL/[min · g]; P<0.05). Myocardial (123)I-ZIROT extraction tracked regional myocardial flow better than either thallium-201 or (99m)Tc-sestamibi from previous studies using a similar model. Furthermore, the (123)I-ZIROT LAD/LCx activity ratios by ex vivo imaging or well counting (mean±SEM, 0.42±0.08 and 0.45±0.1, respectively) only slightly underestimated the LAD/LCx microsphere flow ratio (0.32±0.09). The ability of (123)I-ZIROT to more linearly track blood flow over a wide range makes it a promising new SPECT myocardial perfusion imaging agent with potential for improved coronary artery disease detection and better quantitative estimation of the severity of flow impairment.

Biophysical Model of the Spatial Heterogeneity of Myocardial Flow

The blood flow in the myocardium has significant spatial heterogeneity. The objective of this study was to develop a biophysical model based on detailed anatomical data to determine the heterogeneity of regional myocardial flow during diastole. The model predictions were compared with experimental measurements in a diastolic porcine heart in the absence of vessel tone using nonradioactive fluorescent microsphere measurements. The results from the model and experimental measurements showed good agreement. The relative flow dispersion in the arrested, vasodilated heart was found to be 44% and 48% numerically and experimentally, respectively. Furthermore, the flow dispersion was found to have fractal characteristics with fractal dimensions (D) of 1.25 and 1.27 predicted by the model and validated by the experiments, respectively. This validated three-dimensional model of normal diastolic heart will play an important role in elucidating the spatial heterogeneity of coronary blood flow, and serve as a foundation for understanding the interplay between cardiac mechanics and coronary hemodynamics.

Off-Pump Coronary Artery Bypass Leads to a Regional Hypercoagulable State Not Detectable Using Systemic Markers.

OBJECTIVE: It is believed that off-pump coronary artery bypass grafting (OPCAB) leads to hypercoagulability, but efforts to document such a state have been unrevealing. We hypothesized that OPCAB increases the risk of developing a regional hypercoagulable state. METHODS: Blood was obtained from the aorta and coronary sinus (CS) after CABG performed off- (N=69) or on-pump (N=35) to determine the transcardiac gradients of F1.2 (thrombin production), XIIa (coagulation activation), myoglobin (ischemia) and IL-6, IL-8 using ELISA and platelet-derived microparticles using FACS. Platelet function was measured using aggregometry. Regional myocardial pH and SVG flow were recorded intraoperatively. SVG biopsies were analyzed for endothelial integrity (EI) using immunohistochemistry and graft patency was determined by predischarge CT angiography. RESULTS: Compared with on-pump, OPCAB provoked significantly higher transcardiac F1.2 (117±200 v. 31±38%), FXII-a (14±29 v. 2±4%), microparticles (14±-9.5% v. 6.4±-4.1%), IL-6 (119±183 v. 28±39%), and a trend toward increased IL-8 (67±94 v. 24±46%, P = 0.077). Myoglobin release after OPCAB, also greater than on-pump CABG (54±89 v. 8±14%, P < 0.01), correlated with regional pH change (R=-0.96, P < 0.0001), and F1.2 release (R=0.55, P = 0.0002). In contrast, systemic changes in these markers were all less after OPCAB. SVG flow was significantly reduced in OPCAB (39.4 versus 66.5 mL/min, P = 0.0002), but EI and graft patency rates were the same. CONCLUSIONS: Through the use of transcardiac assays, we illustrated that regional coagulation was enhanced after off- compared with on-pump CABG. If the findings of this pilot study are confirmed, OPCAB may require additional antithrombotic therapies to respond to this local hypercoagulable state.

Lower Myocardial Perfusion Reserve Is Associated With Decreased Regional Left Ventricular Function in Asymptomatic Participants of the Multi-Ethnic Study of Atherosclerosis

Myocardial ischemia is an important determinant of regional left ventricular systolic function. Myocardial blood flow reserve may be impaired by cardiovascular disease before alterations of myocardial perfusion at rest become manifest. Nevertheless, the relation between flow reserve and regional myocardial function has not been studied in individuals without a history of clinical heart disease. Seventy-four participants (66+/-9 years, mean+/-SD) of the Multi-Ethnic Study of Atherosclerosis (MESA) underwent myocardial magnetic resonance tagging and contrast-enhanced perfusion studies. Regional myocardial function was evaluated as peak systolic circumferential strain (Ecc) in the three main coronary territories (left anterior descending [LAD], left circumflex, and right coronary artery [RCA]). Myocardial blood flow at rest and during adenosine-induced hyperemia was quantified by contrast-enhanced magnetic resonance imaging, to study the relation between regional flow and function after multivariable adjustment for age, gender, body mass index, left ventricular mass, and traditional risk factors. Lower regional myocardial blood flow during hyperemia was associated with reduced regional left ventricular function expressed as lower Ecc in the RCA (P<0.01) and left circumflex regions (P<0.05) measured in the subendocardium, mid-wall, and subepicardium. In contrast, no significant association was seen in the LAD territory (P=0.16). In addition, segmental function in LAD and RCA regions was reduced when individuals in the lowest 10th percentile for regional myocardial flow reserve were compared with the other participants. Absolute decreases in mid-wall Ecc LAD and RCA and global Ecc were 3.0%, 3.4%, and 2.8%, respectively (P<0.05 for all regions). Lower myocardial flow reserve is related to reduced regional function in asymptomatic individuals.