Impaired Hyperaemic Myocardial Blood Flow Research Articles

Relationship between impaired myocardial blood flow by positron emission tomography and low-attenuation plaque burden and pericoronary adipose tissue attenuation from coronary computed tomography: From the prospective PACIFIC trial

BackgroundPositron emission tomography (PET) is the clinical gold standard for quantifying myocardial blood flow (MBF). Pericoronary adipose tissue (PCAT) attenuation may detect vascular inflammation indirectly. We examined the relationship between MBF by PET and plaque burden and PCAT on coronary CT angiography (CCTA). MethodsThis post hoc analysis of the PACIFIC trial included 208 patients with suspected coronary artery disease (CAD) who underwent [15O]H2O PET and CCTA. Low-attenuation plaque (LAP, < 30HU), non-calcified plaque (NCP), and PCAT attenuation were measured by CCTA. ResultsIn 582 vessels, 211 (36.3%) had impaired per-vessel hyperemic MBF (≤ 2.30 mL/min/g). In multivariable analysis, LAP burden was independently and consistently associated with impaired hyperemic MBF (P = 0.016); over NCP burden (P = 0.997). Addition of LAP burden improved predictive performance for impaired hyperemic MBF from a model with CAD severity and calcified plaque burden (P < 0.001). There was no correlation between PCAT attenuation and hyperemic MBF (r = − 0.11), and PCAT attenuation was not associated with impaired hyperemic MBF in univariable or multivariable analysis of all vessels (P > 0.1). ConclusionIn patients with stable CAD, LAP burden was independently associated with impaired hyperemic MBF and a stronger predictor of impaired hyperemic MBF than NCP burden. There was no association between PCAT attenuation and hyperemic MBF.

Machine learning from quantitative coronary computed tomography angiography predicts ischemia and impaired myocardial blood flow

Abstract Background Atherosclerotic plaque characteristics influence the hemodynamic consequences of coronary lesions. This study sought to assess the performance of a machine learning (ML) score integrating coronary computed tomography angiography (CCTA)-based quantitative plaque features for the prediction of ischemia by invasive fractional flow reserve (FFR) and impaired myocardial blood flow (MBF) by [15O]H2O positron emission tomography (PET). Methods This post-hoc analysis of the PACIFIC (Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography) trial included 208 patients with suspected coronary artery disease who underwent CCTA, [15O]H2O PET, and 3-vessel invasive FFR. Plaque quantification from CCTA was performed using semiautomated software. A boosted ensemble ML algorithm (XGBoost) trained on data from the NXT (Analysis of Coronary Blood Flow using CT Angiography: Next Steps) trial was used to develop a ML score for the prediction of per-vessel ischemia (invasive FFR ≤0.80). The performance of the ML score was evaluated in 551 vessels from the PACIFIC trial for external validation. Thereafter, we assessed the discriminative ability of the ML score for per-vessel impaired hyperemic MBF (≤2.30 mL/min/g). Results In total, 138 (25.0%) vessels had ischemia and 195 (35.4%) vessels had impaired hyperemic MBF. CCTA-derived quantitative percent diameter stenosis and low-density noncalcified plaque (LDNCP) volume were higher in ischemic vessels compared with non-ischemic vessels (60.8% vs. 19.9%; and 42.3 mm3 vs. 9.1 mm3; both p&amp;lt;0.001). The ML score demonstrated a significantly higher area under the receiver-operating characteristic curve (AUC) for predicting ischemia (0.92, 95% confidence interval [CI] 0.89–0.94) compared with visual stenosis grade (0.84, 95% CI 0.80–0.87; p&amp;lt;0.001). Overall, quantitative percent diameter stenosis and LDNCP volume had greatest feature importance for ML, followed by percent area stenosis, minimum luminal diameter, and contrast density drop (Figure 1). An individualized explanation of ML ischemia prediction is shown in Figure 2. When applied for impaired MBF discrimination, the ML score exhibited an AUC of 0.82 (95% CI 0.78–0.85) and was superior to visual stenosis grade (AUC 0.76, 95% CI 0.72–0.80; p=0.03). Conclusions An externally validated ML score integrating CCTA-based quantitative plaque features accurately predicts FFR-defined ischemia and abnormal MBF by PET, outperforming standard visual CCTA interpretation. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung, and Blood Institute, United States Performance of the ML scoreIndividual explanation of ML prediction

Effect of Plaque Burden and Morphology on Myocardial Blood Flow and Fractional Flow Reserve

BackgroundAtherosclerotic plaque characteristics may affect downstream myocardial perfusion, as well as coronary lesion severity. ObjectivesThis study sought to evaluate the association between quantitative plaque burden and plaque morphology obtained using coronary computed tomography angiography (CTA) and quantitative myocardial perfusion obtained using [15O]H2O positron emission tomography (PET), as well as fractional flow reserve (FFR) derived invasively. MethodsTwo hundred eight patients (63% men; age 58 ± 8.7 years) with suspected coronary artery disease were prospectively included. All patients underwent 256-slice coronary CTA, [15O]H2O PET, and invasive FFR measurements. Coronary CTA-derived plaque burden and morphology were assessed using commercially available software and compared with PET perfusion and FFR. ResultsAtherosclerotic plaques were present in 179 patients (86%) and 415 of 610 (68%) evaluable coronary arteries. On a per-vessel basis, traditional coronary plaque burden indexes, such as plaque length and volume, minimal lumen area, and stenosis percentage, were significantly associated with impaired hyperemic myocardial blood flow (MBF) and FFR. In addition, morphological features, such as partially calcified plaques, positive remodeling (PR), and low attenuation plaque, displayed a negative impact on hyperemic MBF and FFR. Multivariable analysis revealed that the morphological feature of PR was independently related to impaired hyperemic MBF as well as an unfavorable FFR (p = 0.004 and p = 0.007, respectively), next to stenosis percentage (p = 0.001 and p < 0.001, respectively) and noncalcified plaque volume (p < 0.001 and p = 0.010, respectively). ConclusionsPR and noncalcified plaque volume are associated with detrimental downstream hyperemic myocardial perfusion and FFR, independent of lesion severity.

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...

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.

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.

IMPAIRED HYPEREMIC MYOCARDIAL BLOOD FLOW IS ASSOCIATED WITH INDUCIBILITY OF VENTRICULAR ARRHYTHMIA IN ISCHEMIC CARDIOMYOPATHY

Risk stratification for ventricular arrhythmias (VA) is important to refine selection criteria for primary prevention implantable cardioverter-defibrillator therapy. Impaired hyperemic myocardial blood flow (MBF) is associated with increased mortality rate in ischemic and non-ischemic cardiomyopathy

Impaired Hyperemic Myocardial Blood Flow Is Associated With Inducibility of Ventricular Arrhythmia in Ischemic Cardiomyopathy

Risk stratification for ventricular arrhythmias (VAs) is important to refine selection criteria for primary prevention implantable cardioverter defibrillator therapy. Impaired hyperemic myocardial blood flow (MBF) is associated with increased mortality rate in ischemic and nonischemic cardiomyopathy, which may be attributed to electric instability inducing VAs. The aim of this pilot study was to assess whether hyperemic MBF impairment may be related with VA inducibility in patients with ischemic cardiomyopathy. Thirty patients with ischemic cardiomyopathy referred for primary prevention implantable cardioverter defibrillator implantation were prospectively included (26 men; 65±8 years old; left ventricular ejection fraction, 29±6%). [15O]H2O positron-emission tomography was performed to quantify resting MBF, hyperemic MBF, and coronary flow reserve. Left ventricular dimensions, function, and scar burden were assessed with cardiovascular magnetic resonance imaging. An electrophysiological study was performed to test VA inducibility. Positive electrophysiological study patients (n=12) showed reduced hyperemic MBF (1.25±0.30 versus 1.66±0.38 mL·min(-1)·g(-1); P<0.01) and coronary flow reserve (1.59±0.49 versus 2.12±0.48; P<0.01) compared with electrophysiological study negative patients (n=18). In electrophysiological study positive patients, the number of scar segments>75% transmurality was higher (P<0.05), although scar size and border zone did not differ. Receiver-operating characteristic curve analysis indicated that impaired hyperemic MBF (area under the curve, 0.84; 95% confidence intervals [0.69-0.99]) and coronary flow reserve (area under the curve, 0.77; 95% confidence intervals [0.57-0.96]) were associated with VA inducibility. In this pilot study, impaired hyperemic MBF and coronary flow reserve were associated with VA inducibility in patients with ischemic cardiomyopathy. These results are hypothesis generating for a potential role of quantitative positron-emission tomography perfusion imaging in risk stratification for VAs.

Insulin resistance is a major determinant of myocardial blood flow impairment in anginal patients.

In patients with chest pain, stress-induced myocardial perfusion abnormalities are often the result of depressed myocardial blood flow (MBF) reserve. We investigated the relative contribution of cardiovascular risk factors and coronary atherosclerosis to MBF abnormalities in anginal patients. We studied 167 patients with typical (n = 100) or atypical (n = 67) chest pain who underwent quantitative evaluation of MBF by PET at rest and after dipyridamole infusion, and quantitative coronary angiography (invasive or by 64-slice CT). Patients with left ventricular (LV) dysfunction (ejection fraction <45%) were excluded. Coronary atherosclerosis of ≥50% was defined as obstructive. At rest median MBF was 0.60mlmin-1g-1, and after dipyridamole infusion median MBF was 1.22mlmin-1g-1. MBF reserve was <2 in 77 of 167 patients (46%). Coronary atherosclerosis was present in 67 patients (40%), 26 with obstructive disease. In a univariate analysis several variables were associated with reduced MBF at rest, including male gender, coronary atherosclerosis and elevated LV end-diastolic diameter, and during hyperaemia, including male gender, insulin resistance (IR), smoking habit, LV ejection fraction and end-diastolic diameter. In a multivariate analysis, after adjustment for LV function and for pharmacological treatments, male gender was the only independent predictor of reduced MBF at rest (P < 0.001), while male gender (P = 0.003), IR (P = 0.033) and coronary atherosclerosis (P < 0.001) remained the only independent predictors of reduced hyperaemic MBF. IR (P = 0.043) and coronary atherosclerosis (P = 0.005) were the only predictors of depressed MBF reserve. Coronary atherosclerosis, male gender and IR showed additive effects on hyperaemic MBF. In patients with chest pain and normal LV systolic function, IR, male gender and coronary atherosclerosis are independent and additive determinants of impaired hyperaemic MBF.

Inducibility of ventricular arrhythmias is related with impaired hyperaemic myocardial blood flow assessed with [15O]H2O PET in patients with ischaemic cardiomyopathy

Purpose: Prediction of ventricular arrhythmias (VA) is important to refine selection criteria for implantable cardioverter defibrillator (ICD) therapy in patients with ischaemic cardiomyopathy (ICMP). Cardiac positron emission tomography (PET) allows for absolute quantification of myocardial blood flow (MBF) and is increasingly available in clinical practice. Hyperaemic MBF has been demonstrated to predict cardiac death in ischaemic and non-ischaemic cardiomyopathy. However, data on the relationship with VA are lacking. The aim of this study was to assess whether hyperaemic MBF impairment is related with the inducibility of VA in patients with ICMP. Methods: Patients with ICM who were referred for ICD implantation for primary prevention based on current guidelines were included. They underwent [15O]H2O PET assessment of global MBF under both resting and hyperaemic conditions. After implantation, according to standard procedure, the ICD was used to perform an electrophysiological study (EPS) to test the inducibility of VA. EPS was considered positive in case of sustained VA. Results: Twenty-eight patients were included (24 men, age 67±9 years, LVEF 28±7%). Patients (n=10) with positive EPS had significantly reduced global hyperaemic MBF and coronary flow reserve (CFR) compared with EPS negative patients (1.19±0.28 vs. 1.58±0.35 ml/min/g, p<0.01 and 1.55±0.34 vs. 2.05±0.46, p<0.01, respectively). No significant differences were found in age, sex, LVEF, creatinine, NT-proBNP, NYHA class and resting MBF. ROC-curve analysis demonstrated that hyperaemic MBF (AUC 0.82, 95% CI 0.66-0.99, p<0.01) and CFR (AUC 0.80, 95% CI 0.63-0.97, p=0.01) were predictors for VA inducibility. Univariate analysis revealed that hyperaemic MBF (p=0.02) and CFR (p=0.02) were the only variables significantly associated with a positive EPS. Conclusion: Impaired global hyperaemic MBF and CFR predict inducibility of VA in patients with ICMP. These results suggest that impaired hyperaemic MBF might contribute to electrical instability. Risk stratification for VA might be enhanced by quantitative [15O]H2O PET MBF assessment in ICMP patients.

Determinants of coronary microvascular dysfunction in symptomatic hypertrophic cardiomyopathy

Impaired hyperemic myocardial blood flow (MBF) in hypertrophic cardiomyopathy (HCM), despite normal epicardial coronary arteries, results in microvascular dysfunction. The aim of the present study was to determine the relative contribution of extravascular compressive forces to microvascular dysfunction in HCM. Eighteen patients with symptomatic HCM and normal coronary arteries and 10 age-matched healthy volunteers were studied with PET to quantify resting and hyperemic MBF at a subendocardial and subepicardial level. In HCM patients, MRI was performed to determine left ventricular (LV) mass index (LVMI) and volumes, echocardiography to assess diastolic perfusion time, heart catheterization to measure LV outflow tract gradient (LVOTG) and LV pressures, and serum NH(2)-terminal pro-brain natriuretic peptide (NT-proBNP) as a biochemical marker of LV wall stress. Hyperemic MBF was blunted in HCM vs. controls (2.26 +/- 0.97 vs. 2.93 +/- 0.64 ml min(-1) g(-1), P < 0.05). In contrast to controls (1.38 +/- 0.15 to 1.25 +/- 0.19, P = not significant), the endocardial-to-epicardial MBF ratio decreased significantly in HCM during hyperemia (1.20 +/- 0.11 to 0.88 +/- 0.18, P < 0.01). This pattern was similar for hypertrophied septum and lateral wall. Hyperemic MBF was inversely correlated with LVOTG, NT-proBNP, left atrial volume index, and LVMI (all P < 0.01). Multivariate regression analysis, however, revealed that only LVMI and NT-proBNP were independently related to hyperemic MBF, with greater impact at the subendocardial myocardial layer. Hyperemic MBF is more severely impaired at the subendocardial level in HCM patients. The level of impairment is related to markers of increased hemodynamic LV loading conditions and LV mass. These observations suggest that, in addition to reduced capillary density caused by hypertrophy, extravascular compressive forces contribute to microvascular dysfunction in HCM patients.

834-3 Impaired hyperaemic myocardial blood flow is related to systolic function in idiopathic dilated cardiomyopathy

834-3 Impaired hyperaemic myocardial blood flow is related to systolic function in idiopathic dilated cardiomyopathy

Plasma asymmetric dimethylarginine and hyperemic myocardial blood flow in young subjects with borderline hypertension or familial hypercholesterolemia

ObjectivesThe goal of this study was to examine the relationship between plasma asymmetric dimethylarginine (ADMA) level and hyperemic myocardial blood flow (MBF) in subjects with borderline hypertension (BHT) and familial hypercholesterolemia (FH). BackgroundAsymmetric dimethylarginine is an endogenous competitive inhibitor of nitric oxide synthase that may modulate vascular function. MethodsWe measured plasma ADMA levels and myocardial flow in 77 young men (mean age 35 ± 5 years), including 47 healthy controls, 16 men with BHT, and 14 men with FH. Basal and dipyridamole-induced myocardial flow was measured using positron emission tomography. Plasma ADMA levels were measured using high-pressure liquid chromatography. ResultsAsymmetric dimethylarginine levels were significantly elevated in the BHT group compared with controls (0.59 ± 0.13 μmol/l vs. 0.43 ± 0.12 μmol/l, p < 0.001), and they had significantly lower dipyridamole flow (2.85 ± 1.20 ml/min/g vs. 3.69 ± 1.68 ml/min/g, p < 0.05). In a multivariate regression model adjusted for the study group, dipyridamole flow was inversely associated with ADMA (p < 0.05), age (p < 0.05), and apolipoprotein B concentration (p < 0.05). ConclusionsWe conclude that plasma ADMA concentration is related to dipyridamole-induced vasodilatory function in young men, independently of blood pressure elevation and hypercholesterolemia. Subjects with BHT have significantly increased plasma ADMA levels, which may partly explain the impaired hyperemic MBF in this condition.