Hyperemic Myocardial Blood Flow Research Articles

Noninvasive PET quantitative myocardial blood flow with regadenoson for assessing cardiac allograft vasculopathy in orthotopic heart transplantation patients

BackgroundRisk stratification and early detection of cardiac allograft vasculopathy (CAV) is essential in orthotopic heart transplantation (OHT) patients. This study assesses the changes in myocardial blood flow (MBF) noninvasively in OHT patients using quantitative cardiac PET with regadenoson. MethodsTwelve patients (Group 1) (8 males, 4 females, mean age 55 ± 7 years) with no history of post OHT myocardial ischemia were enrolled 5.4 ± 2.0 years after OHT. Fifteen patients (Group 2) (9 males, 6 females, mean age 71 ± 9 years) with intermediate pretest probability but not documented evidence for coronary artery disease (CAD) were also included to serve as control. Global and regional MBFs were assessed using dynamic 13N-NH3 PET at rest and during regadenoson-induced hyperemia. The coronary flow reserve (CFR) was also calculated as the ratio of hyperemic to resting MBF. ResultsMean regadenoson-induced rate-pressure products were similar in both groups, while there was an increase in resting rate-pressure product in Group 1 patients. Both mean and median values of resting MBF were higher in Group 1 than Group 2 patients (1.33 ± 0.31 and 1.01 ± 0.21 mL/min/g for Groups 1 and 2, respectively, P < .001), while mean hyperemic MBF values were similar in both Groups (2.68 ± 0.84 and 2.64 ± 0.94 mL/min/g, P = NS) but median hyperemic MBF values were lower in Group 1 than Group 2 patients (2.0 vs. 2.60 mL/min/g, P = .018). Both mean and median CFR values demonstrated a significant reduction for Group 1 compared to Group 2 patients (2.07 ± 0.74 vs 2.63 ± 0.48, P = .025). ConclusionsThis study suggests that the MBF in OHT patients may be abnormal at resting state with diminished CFR. This hints that the epicardial and microvascular coronary subsystem may be exacerbated after OHT leading to the gradual progression of CAV.

Positron Emission Tomography-Determined Hyperemic Flow, Myocardial Flow Reserve, and Flow Gradient-Quo Vadis?

Positron emission tomography/computed tomography (PET/CT) applied with positron-emitting flow tracers such as 13N-ammonia and 82Rubidium enables the quantification of both myocardial perfusion and myocardial blood flow (MBF) in milliliters per gram per minute for coronary artery disease (CAD) detection and characterization. The detection of a regional myocardial perfusion defect during vasomotor stress commonly identifies the culprit lesion or most severe epicardial narrowing, whereas adding regional hyperemic MBFs, myocardial flow reserve (MFR), and/or longitudinal flow decrease may also signify less severe but flow-limiting stenosis in multivessel CAD. The addition of regional hyperemic flow parameters, therefore, may afford a comprehensive identification and characterization of flow-limiting effects of multivessel CAD. The non-specific origin of decreases in hyperemic MBFs and MFR, however, prompts an evaluation and interpretation of regional flow in the appropriate context with the presence of obstructive CAD. Conversely, initial results of the assessment of a longitudinal hyperemic flow gradient suggest this novel flow parameter to be specifically related to increases in CAD caused epicardial resistance. The concurrent assessment of myocardial perfusion and several hyperemic flow parameters with PET/CT may indeed open novel avenues of precision medicine to guide coronary revascularization procedures that may potentially lead to a further improvement in cardiovascular outcomes in CAD patients.

Reproducible Computer-Assisted Quantification of Myocardial Perfusion with Contrast-Enhanced Ultrasound

Myocardial perfusion can be quantified by myocardial contrast echocardiography (MCE) and is used for the diagnosis of coronary artery disease (CAD). However, existing MCE quantification software is highly operator dependent and has poor reproducibility and ease of usage. The aim of this study was to develop robust and easy-to-use software that can perform MCE quantification accurately, reproducibly and rapidly. The developed software has the following features: (i) semi-automatic segmentation of the myocardium; (ii) automatic rejection of MCE data with poor image quality; (iii) automatic computation of perfusion parameters such as myocardial blood flow (MBF). MCE sequences of 18 individuals (9 normal, 9 with CAD) undergoing vasodilator stress with dipyridamole were analysed quantitatively using the software. When evaluated against coronary angiography, the software achieved a sensitivity of 71% and a specificity of 91% for hyperemic MBF. With the automatic rejection algorithm, the sensitivity and specificity further improved to 77% and 94%, respectively. For MBF reproducibility, the percentage agreement is 85% (κ = 0.65) for inter-observer variability and 88% (κ = 0.72) for intra-observer variability. The intra-class correlation coefficients are 0.94 (inter-observer) and 0.96 (intra-observer). The time taken to analyse one MCE sequence using the software is about 3 min on a PC. The software has exhibited good diagnostic performance and reproducibility for CAD detection and is rapid and user-friendly.

Physiologic mechanism of discordance between instantaneous wave-free ratio and fractional flow reserve: Insight from 13N-ammonium positron emission tomography

BackgroundInvasive physiologic indices, such as fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR), are used in clinical practice. We sought to evaluate the physiological mechanism of discordance between iFR and FFR using 13N-ammonia positron emission tomography (PET)-derived quantitative parameters. MethodsData from 113 patients, who underwent both 13N-ammonia PET and invasive FFR and iFR measurement, were analyzed. Coronary circulatory indices, such as myocardial blood flow (MBF), coronary flow reserve (CFR), microvascular resistance, and trans-stenosis resistance were compared between patients with discordant results (low FFR despite high iFR) and those with concordant abnormal results (low FFR and low iFR), using cut-off values of FFR≤0.80 and iFR<0.90, respectively. ResultsAmong the 113 patients, 39 (34.5%) showed concordant abnormal results in FFR and iFR measurement, and 17 (15.0%) showed discordant results between FFR and iFR (low FFR and high iFR). In comparison of coronary circulatory indices between discordant group and concordant abnormal group, both showed similar resting MBF (p=0.360), however, the discordant group showed higher hyperemic MBF and CFR, compared with the concordant abnormal group (p=0.003 and p<0.001, respectively). Trans-stenosis resistance was lower in the discordant group, in both resting and hyperemic status (p<0.001 for both). Although the discordant group showed higher resting microvascular resistance, these patients showed significantly higher reduction of microvascular resistance at hyperemia. ConclusionsPatients with low FFR despite high iFR showed significant differences in microvascular resistance, trans-stenosis resistance, absolute MBF, and CFR compared to those with concordant abnormal results between FFR and iFR.

INCREMENTAL PROGNOSTIC VALUE OF CORONARY CALCIUM SCORING IN PATIENTS UNDERGOING 82-RUBIDIUM MYOCARDIAL PERFUSION IMAGING

Introduction: Coronary artery calcium (CAC) score and hyperaemic myocardial blood flow (HMBF) have been associated with clinical outcomes. The aim of this analysis is to determine the incremental prognostic value of CAC over HMBF in the prediction of cardiac events. Methods: A total of 2,060

INTEGRATING HYPEREMIC MYOCARDIAL BLOOD FLOW AND CORONARY FLOW RESERVE FOR PREDICTING CARDIOVASCULAR MORTALITY OUTCOMES IN PATIENTS WITH KNOWN OR SUSPECTED ISCHEMIC HEART DISEASE

Background: It is suggested that integrating maximal hyperemic myocardial blood flow (MBF) and coronary flow reserve (CFR), termed coronary flow capacity, allows comprehensive evaluation of patients with known or suspected stable ischemic heart disease (IHD) compared with CFR alone. As

Prevalence of ischaemia in patients with a chronic total occlusion and preserved left ventricular ejection fraction.

Previous studies on invasive assessment of collateral function in patients with a chronic total occlusion (CTO) have displayed only a limited increase in collateral flow and high occurrence of coronary steal during pharmacological stress. This could question the necessity for ischaemia testing prior to revascularization of CTOs in the presence of myocardial viability. The purpose of the present study was to determine the prevalence of perfusion impairments in patients with a CTO as assessed by [15O]H2O positron emission tomography (PET). Seventy-six consecutive patients (60 men, 62 ± 10 years) with a documented CTO and preserved left ventricular ejection fraction (LVEF) were included. All patients underwent PET to assess (hyperaemic) myocardial blood flow (MBF) and coronary flow reserve (CFR). Collateral connection score was 0 in 7 (9%), 1 in 13 (17%), and 2 in 56 (74%) of the cases, with predominantly a high Rentrop grade (96% ≥2). MBF of the target area during hyperaemia was significantly lower when compared with the remote area (1.37 ± 0.37 vs. 2.63 ± 0.71 mL min-1 g-1, P < 0.001). Target to remote ratio during hyperaemia was on average 0.54 ± 0.13, and 73 (96%) patients demonstrated a significantly impaired target to remote ratio (≤0.75). Only 7 (9%) patients displayed a preserved CFR of ≥2.50, whereas coronary steal (CFR <1.0) was observed in 10 (13%) patients. Even in the presence of angiographically well-developed collateral arteries, the vast majority of CTO patients with a preserved LVEF showed significantly impaired perfusion. These results suggest that collateral function during increased blood flow demand in viable myocardium is predominantly insufficient.

Evaluation of myocardial blood flow and coronary flow reserve after implantation of a bioresorbable vascular scaffold versus metal drug-eluting stent: an interim one-month analysis of the VANISH trial.

A randomised clinical trial of bioresorbable vascular scaffold (BVS) vs. metal drug-eluting stent (DES) was initiated, using positron emission tomography (PET) perfusion imaging to assess the effects of both treatments on (hyperaemic) myocardial blood flow (MBF) and coronary flow reserve (CFR) over a three-year period (VANISH trial). In the present study, early, i.e., after one month, MBF and CFR are reported. Sixty patients (45 men [75%], 55±7 years) with a documented single-vessel type A or B1 lesion were included in this single-blind randomised clinical trial. Patients were randomised to implantation of a BVS or DES in a one-to-one fashion. Approximately one month after percutaneous coronary intervention, patients underwent [15O]H2O PET to assess (hyperaemic) MBF, cold pressor test MBF, and CFR. One patient refused PET perfusion at one-month follow-up (in the DES arm). MBF of the treated myocardial territory during rest, CPT, and hyperaemia were not different in BVS-treated patients as compared to DES-treated patients (1.02±0.28 vs. 0.96±0.24 mL·min-1·g-1, p=0.38, 1.20±0.38 vs. 1.08±0.23 mL·min-1·g-1, p=0.16, and 3.04±0.80 vs. 3.33±0.77 mL·min-1·g-1, p=0.16, respectively). CFR of the treated myocardial territory was significantly lower in the BVS-treated patients (3.09±0.94 vs. 3.57±0.85, p<0.05). No differences in PET-derived absolute myocardial perfusion were observed between BVS-treated patients as compared to DES-treated patients at one-month follow-up. CFR was attenuated in BVS-treated patients, although still within the normal range.

Computed tomography myocardial perfusion vs 15O-water positron emission tomography and fractional flow reserve

ObjectivesComputed tomography (CT) can perform comprehensive cardiac imaging. We compared CT coronary angiography (CTCA) and CT myocardial perfusion (CTP) with 15O-water positron emission tomography (PET) and invasive coronary angiography (ICA) with fractional flow reserve (FFR).Methods51 patients (63 (61–65) years, 80 % male) with known/suspected coronary artery disease (CAD) underwent 320-multidetector CTCA followed by “snapshot” adenosine stress CTP. Of these 22 underwent PET and 47 ICA/FFR. Obstructive CAD was defined as CTCA stenosis >50 % and CTP hypoperfusion, ICA stenosis >70 % or FFR <0.80.ResultsPET hyperaemic myocardial blood flow (MBF) was lower in obstructive than non-obstructive territories defined by ICA/FFR (1.76 (1.32–2.20) vs 3.11 (2.44–3.79) mL/(g/min), P < 0.001) and CTCA/CTP (1.76 (1.32–2.20) vs 3.12 (2.44–3.79) mL/(g/min), P < 0.001). Baseline and hyperaemic CT attenuation density was lower in obstructive than non-obstructive territories (73 (71–76) vs 86 (84–88) HU, P < 0.001 and 101 (96–106) vs 111 (107–114) HU, P 0.001). PET hyperaemic MBF corrected for rate pressure product correlated with CT attenuation density (r = 0.579, P < 0.001). There was excellent per-patient sensitivity (96 %), specificity (85 %), negative predictive value (90 %) and positive predictive value (94 %) for CTCA/CTP vs ICA/FFR.ConclusionCT myocardial attenuation density correlates with 15O-water PET MBF. CTCA and CTP can accurately identify obstructive CAD.Key Points•CT myocardial perfusion can aid the assessment of suspected coronary artery disease.• CT attenuation density from “snapshot” imaging is a marker of myocardial perfusion.• CT myocardial attenuation density correlates with15O-water PET myocardial blood flow.• CT attenuation density is lower in obstructive territories defined by invasive angiography.• Diagnostic accuracy of CTCA+CTP is comparable to invasive angiography + fractional flow reserve.

Myocardial Microvascular Responsiveness During Acute Cardiac Sympathectomy Induced by Thoracic Epidural Anesthesia

To evaluate the effect of acute cardiac sympathectomy by thoracic epidural anesthesia on myocardial blood flow and microvascular function. A prospective observational study. The study was conducted in a tertiary teaching hospital. Ten patients with a mean age of 48 years (range 22-63 years) scheduled for thoracic surgery. Myocardial contrast echocardiography was used to study myocardial blood flow and microvascular responsiveness at rest, during adenosine-induced hyperemia, and after sympathetic stimulation by the cold pressor test. Repeated measurements were performed without and with thoracic epidural anesthesia. An increased myocardial blood volume was observed with thoracic epidural anesthesia compared to baseline (from 0.08±0.02 to 0.10±0.03 mL/mL; p = 0.02). No difference existed in resting myocardial blood flow between baseline conditions and epidural anesthesia (0.85±0.24 v 1.03±0.27 mL/min/g, respectively). Hyperemia during thoracic epidural anesthesia increased myocardial blood flow to 4.31±1.07 mL/min/g (p = 0.0008 v baseline) and blood volume to 0.17±0.04 mL/mL (p = 0.005 baseline). After sympathetic stimulation, no difference in myocardial blood flow parameters was observed CONCLUSIONS: Acute cardiac sympathectomy by thoracic epidural anesthesia increased the blood volume in the myocardial capillary system. Also, thoracic epidural anesthesia increased hyperemic myocardial blood flow, indicating augmented endothelial-independent vasodilator capacity of the myocardium.

Effect of CPAP Withdrawal on myocardial perfusion in OSA: A randomized controlled trial.

Obstructive sleep apnoea (OSA) is highly prevalent and associated with an increased incidence of cardiovascular events. Endothelial dysfunction is the proposed causative mechanism. Continuous positive airway pressure (CPAP) is presumed to improve cardiovascular outcome in OSA. CPAP withdrawal was recently shown to lead to peripheral endothelial dysfunction. However, it is not known whether short-term CPAP withdrawal reduces myocardial perfusion in OSA. In this double-blind randomized controlled study, 45 patients with moderate to severe OSA previously adherent to CPAP were assigned to either subtherapeutic or continuing therapeutic CPAP for 2 weeks. The primary outcome was adenosine-induced myocardial blood flow (MBF) as a measure of endothelial function, assessed by (13) N-ammonia positron emission tomography. Secondary outcomes were measures of dermal and renal microvascular function, morning blood pressure (BP) and heart rate. Despite return of OSA associated with significant increases in BP (+9.1 mm Hg, 95% CI +4.9 to +13.4 mm Hg, P < 0.001) and heart rate (+9.6 bpm, 95% confidence interval (CI) +4.6 to +14.6 bpm, P < 0.001), CPAP withdrawal had no significant effect on maximal myocardial perfusion capacity (hyperaemic MBF -0.01 ml/min/g, 95% CI -0.33 to +0.24 ml/min/g, P = 0.91), nor renal and dermal microvascular function. In patients with OSA, a short-term CPAP withdrawal does not lead to detectable impairment of coronary endothelial function, as has been demonstrated in the brachial artery, despite a clinically relevant increase in BP of nearly 10 mm Hg. There was also no evidence of an impairment of renal or dermal microvascular function.

Non-invasive imaging to identify susceptibility for ventricular arrhythmias in ischaemic left ventricular dysfunction

ObjectiveNon-invasive imaging of myocardial perfusion, sympathetic denervation and scar size contribute to enhanced risk prediction of ventricular arrhythmias (VA). Some of these imaging parameters, however, may be intertwined as they...

Quantitative relationship between coronary artery calcium and myocardial blood flow by hybrid rubidium-82 PET/CT imaging in patients with suspected coronary artery disease

BackgroundWe assessed the relationship between coronary artery calcium (CAC) score, myocardial blood flow (MBF) and coronary flow reserve (CFR) in patients undergoing hybrid 82Rb positron emission tomography (PET)/computed tomography (CT) imaging for suspected CAD. We also evaluated if CAC score is able to predict a reduced CFR independently from conventional coronary risk factors. MethodsA total of 637 (mean age 58 ± 13 years) consecutive patients were studied. CAC score was measured according to the Agatston method and patients were categorized into 4 groups (0, 0.01-99.9, 100-399.9, and ≥400). Baseline and hyperemic MBF were automatically quantified. CFR was calculated as the ratio of hyperemic to baseline MBF and it was considered reduced when <2. ResultsGlobal CAC score showed a significant inverse correlation with hyperemic MBF and CFR (both P < .001), while no correlation between CAC score and baseline MBF was found. At multivariable logistic regression analysis age, diabetes and CAC score were independently associated with reduced CFR (all P < .001). The addition of CAC score to clinical data increased the global chi-square value for predicting reduced CFR from 81.01 to 91.13 (P < .01). Continuous net reclassification improvement, obtained by adding CAC score to clinical data, was 0.36. ConclusionsCAC score provides incremental information about coronary vascular function over established CAD risk factors in patients with suspected CAD and it might be helpful for identifying those with a reduced CFR.

Abstract 10869: Role of Myocardial Perfusion, Sympathetic Denervation, and Scar Size in Predicting Inducibility of Ventricular Arrhythmia in Ischemic Cardiomyopathy

Introduction: Myocardial perfusion, scar size, sympathetic denervation and innervation-perfusion mismatch, obtained from positron emission tomography (PET) and late gadolinium enhanced cardiovascular magnetic resonance imaging (LGE-CMR), may all provide better risk prediction of ventricular arrhythmias (VA). There may, however, be overlap between these risk markers, as some are based on similar pathophysiology. The aim of this study was to assess the role of PET and LGE-CMR derived risk markers in predicting VA inducibility in the same patient population. Methods: Patients (n=52, 66 ± 9 years, 90% male, LVEF 29 ± 6%) with ischemic cardiomyopathy and left ventricular ejection fraction (LVEF) ≤35% who were referred for primary prevention implantable cardioverter-defibrillator (ICD) implantation were included. LGE-CMR was performed to assess LV volumes, function, and scar size. [ 15 O]H 2 O PET and [ 11 C]HED PET were performed to assess both resting and hyperemic myocardial blood flow (MBF), and sympathetic innervation. Perfusion and innervation defects, and mismatch were calculated. After ICD implantation, an electrophysiological study (EPS) was performed and was considered positive in case of sustained VA. Results: Patients with positive EPS (n=25) showed lower hyperemic MBF (1.36 ± 0.39 vs. 1.71 ± 0.39 mL·min -1 ·g -1 , P =0.003), larger innervation defect size (28 ± 12 vs. 21 ± 13%, P =0.048), and tended to have larger scar size (24 ± 13 vs. 18 ± 9 g, P =0.07) and perfusion defect size (22 ± 13 vs. 15 ± 11%, P =0.06) compared with EPS negative patients (n=27). No differences were observed in LV volumes, LVEF, and innervation-perfusion mismatch size. Multivariable analysis revealed that impaired hyperemic MBF was the only independent predictor for VA inducibility (OR 0.78, 95% CI 0.65-0.94, P =0.007). A combination of risk markers did not yield incremental predictive value over hyperemic MBF alone. Conclusion: Of all previously validated risk markers for VA, impaired hyperemic MBF was the only independent predictor of VA inducibility. Moreover, a combined approach of different imaging variables did not have incremental value. These results may suggest that quantitative PET perfusion imaging may be promising for risk prediction of VA.

Coronary vasomotor function in infarcted and remote myocardium after primary percutaneous coronary intervention

ObjectiveIn patients with acute myocardial infarction (AMI), coronary vasomotor function is impaired in the myocardial territory supplied by the culprit artery and in remote myocardium supplied by angiographically normal vessels....

SYMPATHETIC DENERVATION IS ASSOCIATED WITH MICROVASCULAR DYSFUNCTION IN NON-INFARCTED MYOCARDIUM IN PATIENTS WITH CARDIOMYOPATHY

Sympathetic denervation typically occurs in the infarcted myocardium and is associated with sudden cardiac death. Impaired innervation was also demonstrated in non-infarcted myocardium in ischaemic and dilated cardiomyopathy (ICMPandDCMP). Factors affecting sympatheticnerveintegrity inremotemyocardium areunknown. Perfusionabnor- malities,evenintheabsenceofepicardialcoronaryarterydisease,mayrelatetosympatheticdysfunction.Thisstudywas aimed to assess the interrelations of myocardial blood flow (MBF), contractile function, and sympathetic innervation in non-infarcted remote myocardium. Seventy patients with ICMP or DCMP and LVEF ≤35% were included. ( 15 O)H2O- and ( 11 C)hydroxyephedrine (HED)PETwasperformedtoquantify restingMBF,hyperaemicMBF,andsympatheticinnervation.Cardiovascularmag- neticresonance(CMR)imagingwasperformedtoassessleftventricularfunction,mass,wallthickening,andscarsize.Wall thickening, ( 11 C)HED retention index (RI), and MBF wereassessed in remote segments without scar, selected on CMR. ( 11 C)HEDRIwascorrelatedwithrestingMBF(r ¼ 0.41,P , 0.001)andhyperaemicMBF(r ¼ 0.55,P , 0.001)inremote myocardiuminbothICMPandDCMP.Inaddition,LVvolumes(r ¼ 20.40,P ¼ 0.001),LVmass(r ¼ 20.31,P ¼ 0.008), andwallthickening(r ¼ 0.45,P , 0.001)correlatedwithremote( 11 C)HEDRI.Multivariableanalysisrevealedthathyper- aemic MBF (B ¼ 0.79, P , 0.001), wall thickening (B ¼ 0.01, P ¼ 0.03), and LVEDV (B ¼ 20.03, P ¼ 0.02) were inde- pendent predictors for remote ( 11 C)HED RI. Conclusion Hyperaemic MBF is independently associated with sympathetic innervation in non-infarcted remote myocardium in patients with ICMP and DCMP. This suggests that microvascular dysfunction might be an important factor related to sympathetic nerve integrity. Whether impaired hyperaemic MBF is the primary cause of this relation remains unclear.

Usefulness of N-terminal Pro–brain Natriuretic Peptide and Myocardial Perfusion in Asymptomatic Adults (from the Multi-Ethnic Study of Atherosclerosis)

This study sought to investigate the relation between myocardial perfusion and N-terminal pro-brain natriuretic peptide (NT-proBNP) in asymptomatic adults without overt coronary artery disease. NT-proBNP is a cardiac neurohormone secreted from the ventricles in response to ventricular volume expansion and pressure overload and may also be elevated in the setting of reduced myocardial perfusion. We hypothesized that reduced myocardial perfusion reserve (MPR) would be associated with elevated NT-proBNP in participants free of overt cardiovascular disease. MPR was measured by cardiac magnetic resonance, before and after adenosine infusion, in 184 MESA participants (mean age 60 ± 10.4, 58% white, 42% Hispanic, 44% women) without overt cardiovascular disease. MPR was modeled as hyperemic myocardial blood flow (MBF) adjusted for MBF at rest. A linear regression analysis, adjusted for demographics, established cardiovascular risk factors, left ventricular mass, coronary calcium score, body mass index, and medications, was used to determine the association between MPR and NT-proBNP. Participants with low hyperemic MBF were more likely to be older, male, diabetic, and have higher blood pressure and higher coronary artery calcium score. Mean hyperemic MBF was 3.04 ± 0.829 ml/min/g. MPR was inversely associated with NT-proBNP levels. In a fully adjusted model, every 1-SD decrement in MPR was associated with a 21% increment in NT-proBNP (p = 0.04). In conclusion, MPR is inversely associated with NT-proBNP level in this cross-sectional study of asymptomatic adults free of overt coronary artery disease, suggesting that higher NT-proBNP levels may reflect subclinical myocardial microvascular dysfunction.

Relative myocardial blood flow by dynamic computed tomographic perfusion imaging predicts hemodynamic significance of coronary stenosis better than absolute blood flow.

Quantitative myocardial perfusion imaging by computed tomography (CT) was recently introduced to calculate myocardial blood flow (MBF). Because absolute MBF thresholds may be affected by technique, methodology, and the microvasculature, we investigated whether a relative measure of MBF improves accuracy to identify hemodynamically significant coronary stenosis. In this prospective study, 42 patients (mean [SD] age, 62.3[8.7] years; 8 women) with suspected or known coronary disease underwent dynamic CT myocardial perfusion imaging using adenosine vasodilation, before invasive angiography (coronary angiography) with fractional flow reserve (FFR). Within each myocardial territory MBF, the MBF relative to remote myocardium (MBFratio) was calculated and compared with coronary angiography and FFR. Of the 91 vessels interrogated by FFR (median, 0.81; interquartile range, 0.73-0.94), 45 vessels (49%) had an FFR value lower than 0.8 and were considered hemodynamically significant. Hyperemic MBF was lower in ischemic territories: 75.6 ± 22.5 mL per 100 mL/min versus 98.3 ± 23.1 mL per 100 mL/min (P < 0.0001). The MBFratio correlated better with FFR (P = 0.76) than the absolute MBF did (P = 0.52). Receiver operating curve analysis showed better discrimination by MBFratio: area under the curve of 0.85 versus 0.75 (P = 0.02). The MBF of remote myocardium varied between 60.7 and 167.2 mL per 100 mL/min and was lower in patients without heart rate acceleration (P = 0.0035). The MBFratio seems to better identify hemodynamically significant coronary artery disease than does the absolute MBF determined by dynamic CT perfusion imaging. This may be caused by microvascular status or related to the methodology.

Quantitative Assessment of Myocardial Perfusion in the Detection of Significant Coronary Artery Disease: Cutoff Values and Diagnostic Accuracy of Quantitative [15O]H2O PET Imaging

BackgroundRecent studies have demonstrated improved diagnostic accuracy for detecting coronary artery disease (CAD) when myocardial blood flow (MBF) is quantified in absolute terms, but there are no uniformly accepted cutoff values for hemodynamically significant CAD. ObjectivesThe goal of this study was to determine cutoff values for absolute MBF and to evaluate the diagnostic accuracy of quantitative [15O]H2O positron emission tomography (PET). MethodsA total of 330 patients underwent both quantitative [15O]H2O PET imaging and invasive coronary angiography in conjunction with fractional flow reserve measurements. A stenosis >90% and/or fractional flow reserve ≤0.80 was considered obstructive; a stenosis <30% and/or fractional flow reserve >0.80 was nonobstructive. ResultsHemodynamically significant CAD was diagnosed in 116 (41%) of 281 patients who fulfilled study criteria for CAD. Resting perfusion was 1.00 ± 0.25 and 0.92 ± 0.23 ml/min/g in regions supplied by nonstenotic and significantly stenosed vessels, respectively (p < 0.001). During stress, perfusion increased to 3.26 ± 1.04 ml/min/g and 1.73 ± 0.67 ml/min/g, respectively (p < 0.001). The optimal cutoff values were 2.3 and 2.5 for hyperemic MBF and myocardial flow reserve, respectively. For MBF, these cutoff values showed a sensitivity, specificity, and accuracy for detecting significant CAD of 89%, 84%, and 86%, respectively, at a per-patient level and 87%, 85%, and 85% at a per-vessel level. The corresponding myocardial flow reserve values were 86%, 72%, and 78% (per patient) and 80%, 82%, and 81% (per vessel). Age and sex significantly affected diagnostic accuracy of quantitative PET. ConclusionsQuantitative MBF measurements with the use of [15O]H2O PET provided high diagnostic performance, but both sex and age should be taken into account.

Coronary microvascular ischemia in hypertrophic cardiomyopathy - a pixel-wise quantitative cardiovascular magnetic resonance perfusion study.

BackgroundMicrovascular dysfunction in HCM has been associated with adverse clinical outcomes. Advances in quantitative cardiovascular magnetic resonance (CMR) perfusion imaging now allow myocardial blood flow to be quantified at the pixel level. We applied these techniques to investigate the spectrum of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and to explore its relationship with fibrosis and wall thickness.MethodsCMR perfusion imaging was undertaken during adenosine-induced hyperemia and again at rest in 35 patients together with late gadolinium enhancement (LGE) imaging. Myocardial blood flow (MBF) was quantified on a pixel-by-pixel basis from CMR perfusion images using a Fermi-constrained deconvolution algorithm. Regions-of-interest (ROI) in hypoperfused and hyperemic myocardium were identified from the MBF pixel maps. The myocardium was also divided into 16 AHA segments.ResultsResting MBF was significantly higher in the endocardium than in the epicardium (mean ± SD: 1.25 ± 0.35 ml/g/min versus 1.20 ± 0.35 ml/g/min, P < 0.001), a pattern that reversed with stress (2.00 ± 0.76 ml/g/min versus 2.36 ± 0.83 ml/g/min, P < 0.001). ROI analysis revealed 11 (31%) patients with stress MBF lower than resting values (1.05 ± 0.39 ml/g/min versus 1.22 ± 0.36 ml/g/min, P = 0.021). There was a significant negative association between hyperemic MBF and wall thickness (β = −0.047 ml/g/min per mm, 95% CI: −0.057 to −0.038, P < 0.001) and a significantly lower probability of fibrosis in a segment with increasing hyperemic MBF (odds ratio per ml/g/min: 0.086, 95% CI: 0.078 to 0.095, P = 0.003).ConclusionsPixel-wise quantitative CMR perfusion imaging identifies a subgroup of patients with HCM that have localised severe microvascular dysfunction which may give rise to myocardial ischemia.