Lower Myocardial Flow Reserve Research Articles

Sex Differences in Systemic and Coronary Arterial Hemodynamics in Heart Failure With Preserved Ejection Fraction

Heart failure (HF) with preserved ejection fraction (HFpEF) predominantly affects females. Systemic and coronary arterial abnormalities are present in HFpEF and may contribute to HFpEF in females. We performed a cross-sectional study of 32 participants with HFpEF and 26 controls. Arterial hemodynamics were noninvasively assessed by combining arterial tonometry with echocardiography. Coronary microvascular function was assessed by rubidium-82 positron emission tomography as the myocardial flow reserve. Coronary vascular resistance (CVR) at rest and vasodilator stress were calculated using positron emission tomography. CVR reserve was calculated as stress-rest CVR. Multivariable linear regression assessed the associations of female sex with arterial hemodynamics in participants with and without HF, and the association of HF with arterial hemodynamics within each sex stratum. Demographics and left ventricular systolic and diastolic function were similar between males and females. Among those with HFpEF, females had a higher steady and pulsatile arterial load and more impaired (less negative) CVR reserve than males. Conversely, in controls, females had similar hemodynamics to males. We then divided the sample based on sex. Femaleswith HFpEF had a higher pulsatile arterial load and higher stress CVR than control females. Among males, arterial hemodynamics were similar, regardless of HFpEF status. The measures of early pulsatile arterial load were independently associated with higher E/e' and lower myocardial flow reserve in females only. In conclusion, despite similar left ventricular function between sexes, older females with HFpEF are characterized by additional systemic and coronary arterial hemodynamic abnormalities compared with males with HFpEF and similarly aged females without HFpEF.

The potential of dynamic 99mTc-sestamibi cadmium zinc telluride-single-photon emission computed tomography camera assessing myocardial flow reserve in patients with heart failure with preserved ejection fraction.

Coronary microvascular dysfunction (CMD) is related to the pathophysiology, mortality, and morbidity of heart failure with preserved ejection fraction (HFpEF). A novel single-photon emission computed tomography (SPECT) camera with cadmium zinc telluride (CZT) detectors allows for the quantification of absolute myocardial blood flow and myocardial flow reserve (MFR) in patients with coronary artery disease. However, the potential of CZT-SPECT assessing for CMD has never been evaluated in patients with HFpEF. The clinical records of 127 consecutive patients who underwent dynamic CZT-SPECT were retrospectively reviewed. Rest and stress scanning were started simultaneously with 3 and 9 MBq/kg of 99mTc-sestamibi administration, respectively. Dynamic CZT-SPECT imaging data were analysed using a net-retention model with commercially available software. Transthoracic echocardiography was performed in all patients. The MFR value was significantly lower in the HFpEF group (mean ± SEM = 2.00 ± 0.097) than that in the non-HFpEF group (mean ± SEM = 2.74 ± 0.14, P = 0.0004). A receiver operating characteristic analysis indicated that if a cut-off value of 2.525 was applied, MFR could efficiently distinguish HFpEF from non-HFpEF. Heart failure with preserved ejection fraction had a consistently low MFR, regardless of the diastolic dysfunction score. Heart failure with preserved ejection fraction patients with MFR values lower than 2.075 had a significantly higher incidence of heart failure exacerbation. Myocardial flow reserve assessed by CZT-SPECT was significantly reduced in patients with HFpEF. A lower MFR was associated with a higher hospitalization rate in these patients. Myocardial flow reserve assessed by CZT-SPECT has the potential to predict future adverse events and stratify the severity of disease in patients with HFpEF.

Relationships between indicators of prothrombotic activity and coronary microvascular dysfunction in patients with myocardial infarction with obstructive and non-obstructive coronary artery disease

The relationship between prothrombotic activity and coronary microvascular dysfunction (MVD) is limited. This study aimed to perform a comparative analysis of the relationship between prothrombotic activity and MVD in patients with myocardial infarction without obstructive coronary artery disease (MINOCA) and myocardial infarction with obstructive coronary artery disease (MI-CAD).Material and methodsA total of 37 patients were enrolled in the study; the main group included 16 MINOCA patients, and 21 MI-CAD patients were included in the control group. Blood samples for protein C, antithrombin, WF, plasminogen, and homocysteine were performed on the 4th ± 1 day of admission. CZT-SPECT data were used to determine the standard indices of myocardial perfusion dis-orders (SSS, SRS, and SDS), as well as stress and rest myocardial blood flow (MBF), myocardial flow reserve (MFR), and difference flows (DF). MVD was defined as MFR (≤ 1.91 ml/min); coronary slow flow (CSF) was defined as corrected TIMI frame count (21 ± 3).ResultsWe performed a step-by-step analysis of prothrombotic activity of the hemostasis system in binary logistic regression for MINOCA patients to identify factors associated with MVD (MFR ≤ 1.91 ml/min). A predictive model was developed to estimate the probability of reduced MFR. A low MFR is related to only plasminogen in MINOCA patients, whereas only wall motion score index (WMSI) in MI-CAD group was associated with a low MFR.ConclusionThis small-scale study revealed the relationship between indicators of prothrombotic activity and MVD. The key factors that affect MVD in MINOCA patients was plasminogen, whereas, in patients with MI-CAD, WMSI was the key factor. Measurements of MVD may enhance the risk stratification and facilitate future targeting of adjunctive antithrombotic therapies in MINOCA and MI-CAD patients.

WHY IS HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFPEF) MORE COMMON IN WOMEN THAN MEN? EXPLORING ABNORMALITIES IN PULSITILE ARTERIAL LOAD AS DISTINCT FEATURE OF THE HFPEF SYNDROME IN WOMEN

WHY IS HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFPEF) MORE COMMON IN WOMEN THAN MEN? EXPLORING ABNORMALITIES IN PULSITILE ARTERIAL LOAD AS DISTINCT FEATURE OF THE HFPEF SYNDROME IN WOMEN

Posttraumatic Stress Disorder, Myocardial Perfusion, and Myocardial Blood Flow: A Longitudinal Twin Study

BackgroundThe link between posttraumatic stress disorder (PTSD) and ischemic heart disease remains elusive owing to a shortage of longitudinal studies with a clinical diagnosis of PTSD and objective measures of cardiac compromise. MethodsWe performed positron emission tomography in 275 twins who participated in two examinations approximately 12 years apart. At both visits, we obtained a clinical diagnosis of PTSD, which was classified as long-standing (both visit 1 and visit 2), late onset (only visit 2), and no PTSD (no PTSD at both visits). With positron emission tomography, we assessed myocardial flow reserve (MFR), which, in absence of significant coronary stenoses, indexes coronary microvascular function. We compared positron emission tomography data at visit 2 across the three categories of longitudinally assessed PTSD and examined changes between the two visits. ResultsOverall, 80% of the twins had no or minimal obstructive coronary disease. Yet, MFR was depressed in twins with PTSD and was progressively lower across groups with no PTSD (2.13), late-onset PTSD (1.97), and long-standing PTSD (1.93) (p = .01). A low MFR (a ratio <2.0) was present in 40% of the twins without PTSD, in 56% of those with late-onset PTSD, and in 72% of those with long-standing PTSD (p < .001). Associations persisted in multivariable analysis, when examining changes in MFR between visit 1 and visit 2, and within twin pairs. Results were similar by zygosity. ConclusionsLongitudinally, PTSD is associated with reduced coronary microcirculatory function and greater deterioration over time. The association is especially noted among twins with chronic, long-standing PTSD and is not confounded by shared environmental or genetic factors.

Association Between Impaired Myocardial Flow Reserve on 82Rubidium Positron Emission Tomography Imaging and Adverse Events in Patients With Autoimmune Rheumatic Disease.

Coronary microvascular dysfunction has been described in patients with autoimmune rheumatic disease (ARD). However, it is unknown whether positron emission tomography (PET)-derived myocardial flow reserve (MFR) can predict adverse events in this population. Patients with ARD without coronary artery disease who underwent dynamic rest-stress 82Rubidium PET were retrospectively studied and compared with patients without ARD matched for age, sex, and comorbidities. The association between MFR and a composite end point of mortality or myocardial infarction or heart failure admission was evaluated with time to event and Cox-regression analyses. In 101 patients with ARD (88% female, age: 62±10 years), when compared with matched patients without ARD (n=101), global MFR was significantly reduced (median: 1.68 [interquartile range: 1.34-2.05] versus 1.86 [interquartile range: 1.58-2.28]) and reduced MFR (<1.5) was more frequent (40% versus 22%). MFR did not differ among subtypes of ARDs. In survival analysis, patients with ARD and low MFR (MFR<1.5) had decreased event-free survival for the combined end point, when compared with patients with and without ARD and normal MFR (MFR>1.5) and when compared with patients without ARD and low MFR, after adjustment for the nonlaboratory-based Framingham risk score, rest left ventricular ejection fraction, severe coronary calcification, and the presence of medium/large perfusion defects. In Cox-regression analysis, ARD diagnosis and reduced MFR were both independent predictors of adverse events along with congestive heart failure diagnosis and presence of medium/large stress perfusion defects on PET. Further analysis with inclusion of an interaction term between ARD and impaired MFR revealed no significant interaction effects between ARD and impaired MFR. In our retrospective cohort analysis, patients with ARD had significantly reduced PET MFR compared with age-, sex-, and comorbidity-matched patients without ARD. Reduced PET MFR and ARD diagnosis were both independent predictors of adverse outcomes.

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.

Quantitative blood flow evaluation of vasodilation-stress compared with dobutamine-stress in patients with end-stage liver disease using 82Rb PET/CT

BackgroundOur aim was to determine if end-stage liver disease (ESLD) is associated with an attenuated response to vasodilator-stress or dobutamine-stress using 82Rb-PET MPI with blood flow quantification. Methods and ResultsPre-liver transplant patients who had a normal dipyridamole-stress (n = 27) or dobutamine-stress (n = 26) 82Rb PET/CT MPI study with no identifiable coronary artery calcium were identified retrospectively and compared to a prospectively identified low-risk of liver disease dipyridamole-stress control group (n = 20). The dipyridamole-stress liver disease group had a lower myocardial flow reserve (MFR) (1.89 ± 0.79) than the control group (2.79 ± 0.96, P < .05). The dobutamine-stress group had a higher MFR than both other groups (3.69 ± 1.49, P < .05). A moderate negative correlation between MELD score and MFR was demonstrated for the dipyridamole-stress liver disease group (r = − 0.473, P < .05). This correlation was not observed for the dobutamine-stress liver disease group (r = − 0.253, P = .21). The liver failure group as a whole (n = 53) had a higher resting myocardial blood flow (0.97 ± 0.33 mL/min/g) than the control group (0.82 ± 0.26, P < .05). ConclusionDipyridamole demonstrates an attenuated vasodilatory response in ESLD patients compared to a non-ESLD control group related to higher resting blood flow and comparatively reduced stress blood flow. Dobutamine does not demonstrate this effect implying it may be the preferred pharmacologic MPI stress agent for ESLD patients.

Higher incidence of vasodilator-induced left ventricular cavity dilation by PET when compared to treadmill exercise-ECHO in hypertrophic cardiomyopathy

BackgroundVasodilator-induced transient left ventricular cavity dilation (LVCD) by positron emission tomography (PET) is associated with microvascular dysfunction in hypertrophic cardiomyopathy (HCM). Here we assessed whether HCM patients who develop LVCD by PET during vasodilator stress also develop LV cavity dilation by echocardiography (ECHO-LVCD) following exercise stress. MethodsA retrospective analysis of cardiac function and myocardial blood flow (MBF) was conducted in 108 HCM patients who underwent perfusion-PET and exercise-ECHO as part of their clinical evaluation. We performed a head-to-head comparison of LV volumes and ejection fraction (LVEF) at rest and stress (during vasodilator stress, post-exercise), in 108 HCM patients. A ratio > 1.13 of stress to rest LV volumes was used to define PET-LVCD, and a ratio > 1.17 of stress to rest LVESV was used to define ECHO-LVCD. Patients were divided into 2 groups based on the presence/absence of PET-LVCD. MBF and myocardial flow reserve were quantified by PET, and global longitudinal strain (GLS) was assessed by ECHO at rest/stress in the two groups. ResultsPET-LVCD was observed in 51% (n = 55) of HCM patients, but only one patient had evidence of ECHO-LVCD (ratio = 1.36)—this patient also had evidence of PET-LVCD (ratio = 1.20). The PET-LVCD group had lower PET-LVEF during vasodilator stress, but ECHO-LVEF increased in both groups post-exercise. The PET-LVCD group demonstrated higher LV mass, worse GLS at rest/stress, and lower myocardial flow reserve. Incidence of ischemic ST-T changes was higher in the PET-LVCD group during vasodilator stress (42 vs 17%), but similar (30%) in the two groups during exercise. ConclusionPET-LVCD reflects greater degree of myopathy and microvascular dysfunction in HCM. Differences in the cardiac effects of exercise and vasodilators and timing of stress-image acquisition could underlie discordance in ischemic EKG changes and LVCD by ECHO and PET, in HCM.

Defining the prognostic value of [15O]H2O positron emission tomography-derived myocardial ischaemic burden.

Myocardial ischaemic burden (IB) is used for the risk stratification of patients with coronary artery disease (CAD). This study sought to define a prognostic threshold for quantitative [15O]H2O positron emission tomography (PET)-derived IB. A total of 623 patients with suspected or known CAD who underwent [15O]H2O PET perfusion imaging were included. The endpoint was a composite of death and non-fatal myocardial infarction (MI). A hyperaemic myocardial blood flow (hMBF) and myocardial flow reserve (MFR)-derived IB were determined. During a median follow-up time of 6.7 years, 62 patients experienced an endpoint. A hMBF IB of 24% and MFR IB of 28% were identified as prognostic thresholds. Patients with a high hMBF or MFR IB (above threshold) had worse outcome compared to patients with a low hMBF IB [annualized event rates (AER): 2.8% vs. 0.6%, P < 0.001] or low MFR IB [AER: 2.4% vs. 0.6%, P < 0.001]. Patients with a concordant high IB had the worst outcome (AER: 3.1%), whereas patients with a concordant low or discordant IB result had similar and low AERs of 0.5% and 0.9% (P = 0.953), respectively. Both thresholds were of prognostic value beyond clinical characteristics, however, only the hMBF IB threshold remained predictive when adjusted for clinical characteristics and combined use of the hMBF and MFR thresholds. A hMBF IB ≥24% was a stronger predictor of adverse outcome than an MFR IB ≥28%. Nevertheless, classifying patients according to concordance of IB result allowed for the identification of low- and high-risk patients.

High-risk plaque burdens myocardial flow reserve in intermediate coronary artery disease: hybrid analysis of 13N-ammonia PET and coronary CT angiography

Abstract Background 13N-ammonia PET (NH3-PET) can detect myocardial perfusion abnormalities in patients with coronary artery disease (CAD) and also obtain diagnostic quantitative values of absolute myocardial blood flow and myocardial flow reserve (MFR). Low MFR (MFR&amp;lt;2.0) is an independent prognostic factor for major adverse cardiac event in patients with ischemic and non-ischemic heart disease. A feature of low attenuation plaque (LAP) on coronary CT angiography (CCTA) has been known as high-risk plaque (HRP) for acute coronary syndrome even if there is no significant coronary stenosis. The presence of HRP potentially adversely affects MFR, but the hypothesis has not been elucidated. Purpose We aimed to investigate the affect of LAP to MFR in intermediate CAD. Methods One hundred five patients (age 67±9 years, 65% male) with CAD underwent NH3-PET and CCTA within 6 months between April 2015 and March 2019 were enrolled. Based on the results of CCTA, mild and moderate stenosis were defined as 1% to 49% and 50% to 69% stenosis. Ischemic territories for major three vessels were identified by stress/rest NH3-PET images. Finally, 194 coronary arteries with mild to moderate stenosis corresponding to non-ischemic territory were analyzed in this study. LAP was defined as plaques containing CT value less than 90HU. Partially calcified plaques were included in LAP. Entirely calcification plaque without LAP was defined as calcified plaque. MFR for major three vessels were calculated from dynamic scan at stress/rest NH3-PET. Results CCTA showed 80 coronary arteries with LAP (41%), 104 coronary arteries with calcified plaque (54%), 102 vessels with mild stenosis (53%), and 92 vessels with moderate stenosis (47%). MFRs for coronary arteries with LAP were significantly lower than those without LAP (2.1±0.6 vs 2.5±0.6, p&amp;lt;0.0001). The significant difference in MFR between with and without LAP was observed in both mild and moderate stenosis (mild: 2.0±0.6 vs 2.5±0.6, p=0.0015, moderate: 2.1±0.6 vs 2.5±0.6, p&amp;lt;0.0001). In contrast, coronary arteries with calcified plaque had significantly higher MFR than those without (2.5±0.6 vs 2.1±0.6, p&amp;lt;0.0001). In 58 coronary arteries with MFR&amp;lt;2.0, 71% (41/58) had LAP and 24% (14/58) had calcified plaque. In 136 coronary arteries with MFR≥2.0, 29% (39/136) had LAP and 66% (90/136) had calcified plaque. LAP was significantly more frequent in the former and calcified plaque was significantly more frequent in the latter. Conclusion The presence of LAP burdens MFR in mild to moderate CAD. On the other hand, calcified plaque alone had no adverse effect on MFR. LAP is an important sign in CAD risk assessment even without significant coronary stenosis. MFR and stress MPI Funding Acknowledgement Type of funding source: None

Myocardial Flow Reserve by N13 Ammonia Positron Emission Tomography Predicts Post-Heart Transplant Outcomes

Cardiac allograft vasculopathy (CAV) is a pan-arterial disease, characterized by intimal thickening, fibrosis, and decreased coronary blood flow. It is common (50-65% 10 years post-HT) and is among the leading causes of death following heart transplantation (HT). Screening has traditionally evaluated the epicardial coronary arteries and microvascular dysfunction has been largely overlooked. Recent data suggests poor outcomes among HT patients with low myocardial flow reserve (MFR), a parameter capable of assessing microvascular function. We sought to identify the impact of MFR on death, retransplantation (ReTx), or cardiovascular (CV) hospitalization. This prospective study enrolled 181 (206 screened, 3 studies were technically limited, 22 had high rest flows) patients who underwent 13N ammonia PET with CT attenuation correction between 2016-2017. Patients were followed for clinical outcomes including rejection (cellular or antibody mediated rejection [AMR]), graft function, and CAV. The optimal MFR cut off was determined by a receiver operator characteristic curve. Among the cohort, MFR was highly predictive of the combined endpoint (HR 7.58, p<0.001). The ideal MFR cut point was 1.96 (AUC 0.76, 65.2% Sensitivity, 75.2 Specificity, 93.3 NPV). The group with a MFR<1.96 was more predominantly male, older (mean 5 years), further post-HT (mean 1.5 years), with more DM2, more CKD, fewer received ASA, had more prior cellular & AMR, and more had ≥ISHLT CAV 1. Groups had similar cardiac index, EF, and immunosuppression. Those with a MFR<1.96 had an 11% absolute increase in events at 2 years (Figure, HR 10.75, p=0.002). This was consistent for death/ReTx (HR 9.8, p=0.003) and CV hospitalization (HR 11.5, p=0.001). After adjusting for time post-transplant, AMR, and ISHLT CAV, a MFR<1.96 remained the greatest predictor (HR 6.84, p=0.0006). Decreased MFR following heart transplant is associated with an increased risk of death, ReTx, or CV hospitalization.

Hypertensive coronary microvascular dysfunction: a subclinical marker of end organ damage and heart failure.

Hypertension is a well-established heart failure (HF) risk factor, especially in the context of adverse left ventricular (LV) remodelling. We aimed to use myocardial flow reserve (MFR) and global longitudinal strain (GLS), markers of subclinical microvascular and myocardial dysfunction, to refine hypertensive HF risk assessment. Consecutive patients undergoing symptom-prompted stress cardiac positron emission tomography (PET)-computed tomography and transthoracic echocardiogram within 90 days without reduced left ventricular ejection fraction (<40%) or flow-limiting coronary artery disease (summed stress score ≥ 3) were included. Global MFR was quantified by PET, and echocardiograms were retrospectively analysed for cardiac structure and function. Patients were followed over a median 8.75 (Q1-3 4.56-10.04) years for HF hospitalization and a composite of death, HF hospitalization, MI, or stroke. Of 194 patients, 155 had adaptive LV remodelling while 39 had maladaptive remodelling, which was associated with lower MFR and impaired GLS. Across the remodelling spectrum, diastolic parameters, GLS, and N-terminal pro-B-type natriuretic peptide were independently associated with MFR. Maladaptive LV remodelling was associated with increased adjusted incidence of HF hospitalization and death. Importantly, the combination of abnormal MFR and GLS was associated with a higher rate of HF hospitalization compared to normal MFR and GLS [adjusted hazard ratio (HR) 3.21, 95% confidence interval (CI) 1.09-9.45, P = 0.034), including in the adaptive remodelling subset (adjusted HR 3.93, 95% CI 1.14-13.56, P = 0.030). We have demonstrated important associations between coronary microvascular dysfunction and myocardial mechanics that refine disease characterization and HF risk assessment of patients with hypertension based on subclinical target organ injury.

Myocardial Microvascular Dysfunction in Rheumatoid ArthritisQuantitation by 13N-Ammonia Positron Emission Tomography/Computed Tomography.

The goal of this study was to assess the prevalence of myocardial microvascular dysfunction in rheumatoid arthritis (RA) patients without clinical cardiovascular disease and its association with RA characteristics and measures of cardiac structure and function. Participants with RA underwent rest and vasodilator stress N-13 ammonia positron emission tomography and echocardiography. Global myocardial blood flow was quantified at rest and during peak hyperemia. Myocardial flow reserve (MFR) was calculated as peak stress myocardial blood flow/rest myocardial blood flow. A small number of asymptomatic and symptomatic non-RA controls were also evaluated. In RA patients, mean±SD MFR was 2.9±0.8, with 29% having reduced MFR (<2.5). Male sex and higher interleukin-6 were significantly associated with lower MFR, while the use of tumor necrosis factor inhibitors was associated with higher MFR. Lower MFR was associated with higher left ventricle mass index and higher left ventricle volumes but not with ejection fraction or diastolic dysfunction. RA and symptomatic controls had comparable MFR (mean±SD: 2.9±0.8 versus 2.55±0.6; P=0.48). In contrast, MFR was higher in the asymptomatic controls (mean±SD: 3.25±0.7) although not statistically different. Reduced MFR was observed in a third of RA patients without clinical cardiovascular disease and was associated with a measure of inflammation and with higher left ventricle mass and volumes. MFR in RA patients was similar to controls referred for clinical scans (symptomatic controls). Whether reduced MFR contributes to the increased risk for heart failure in RA remains unknown.

A3993 Myocardial flow reserve assessed by Cardiac 82Rb PET/CT is associated with albumin excretion in patients with type 1 diabetes

Objectives: To evaluate 1) myocardial flow reserve (MFR) and coronary artery calcium (CAC) in patients with type 1 diabetes (T1D) with or without albuminuria and in non-diabetic controls; 2) MFR and CAC in patients with T1D and retinopathy. MFR reflects the function of large epicardial arteries and myocardial microcirculation. CAC represents structural aspects of atherosclerosis. Methods: Cross-sectional study in T1D, stratified by normo- (n = 30) and macroalbuminuria (n = 30), and 30 controls. MFR and CAC was evaluated by cardiac 82Rb PET/CT. Results: MFR was similar in normoalbuminurics and controls (3.1 ± 0.8 vs 3.0 ± 0.79; p = 0.74). Macroalbuminurics had lower MFR compared to normoalbuminurics (2.1 ± 0.9 vs 3.1 ± 0.8; p < 0.0001). CAC score (median[IQR]) was higher in normoalbuminurics compared to controls (72[22–247] vs 0[0–81], p = 0.018), and comparable between macro- and normoalbuminurics. MFR was comparable in T1D with simplex retinopathy (n = 24) compared to no retinopathy (n = 12; p = 0.11), but lower in proliferative (n = 23) compared to simplex retinopathy (p = 0.02). CAC score was comparable between groups of retinopathy. Lower MFR was associated with higher CAC, UACR, age, 24-h SBP and lower eGFR. In multivariate regression lower MFR was associated with higher UACR and age, lower eGFR and smoking (R2 = 0.39). Higher CAC was associated with lower MFR, higher age and 24-h SBP (R2 = 0.34). Conclusion: Myocardial microvascular function was comparable in controls and patients with T1D and normoalbuminuria; but impaired in the presence of macroalbuminuria and/or proliferative retinopathy. Coronary calcification was also high, but not explained by albuminuria. This signifies that functional aspects of atherosclerosis correlate to albuminuria and retinopathy to larger extent than the structural.

Coronary artery microvascular dysfunction: Role of sex and arterial load

BackgroundThe prognosis of cardiovascular disease is worse in women than men, and coronary microvascular dysfunction explains the excess cardiovascular risk in women. In addition, age-related increases in pulsatile arterial load are greater in women than men; and lower arterial compliance has been shown to independently predict cardiovascular events. However, whether arterial load differentially affects the coronary microvasculature in men and women remains unknown. We hypothesized that lower arterial compliance would be associated with coronary artery microvascular dysfunction in women. Methods and results285 subjects (60% women, age: 61.2 ± 11.0 yrs) undergoing cardiac 82Rb positron-emission tomography between 2010 and 2013, with ejection fraction ≥50%, no heart failure, dyspnea, coronary artery disease or regional perfusion defects were included. Left ventricular microvascular function was assessed by myocardial flow reserve (MFR). Pulsatile arterial load was estimated by indexed arterial compliance [ACi: (stroke volume/pulse pressure)/BSA]. Multivariable linear regression evaluated associations of arterial compliance with myocardial flow reserve after adjustment for confounders. ACi was lower in women than men [0.39 ± 0.15 vs. 0.52 ± 0.28 (mL/mm Hg)/m2, P < 0.0001]. We found that the effect of ACi on MFR differs by sex: lower ACi was associated with lower MFR in women (β ± SE: 0.20 ± 0.07, P = 0.004) but not in men (0.03 ± 0.11, P = 0.75). ConclusionsLower ACi was associated with altered coronary microvascular function in women, but not in men. Our findings highlight low arterial compliance as a potential link between hypertension, coronary microvascular dysfunction and adverse cardiovascular events in women.

Myocardial blood flow and myocardial flow reserve values in 13N\u2013ammonia myocardial perfusion PET/CT using a time-efficient protocol in patients without coronary artery disease

BackgroundCardiac imaging by means of myocardial Positron Emission Tomography/Computed Tomography (PET/CT) is being used increasingly to assess coronary artery disease, to guide revascularization decisions with more accuracy, and it allows robust quantitative analysis of both regional myocardial blood flow (MBF) and myocardial flow reserve (MFR).Recently, a more time-efficient protocol has been developed in combination with a residual activity correction algorithm in which a stress acquisition is performed directly after completion of the rest acquisition to subtract remaining myocardial radioactivity.The objective of this study is to define flow values of myocardial blood flow (MBF) and Myocardial Flow Reserve (MFR) with 13N–ammonia (13NH3) myocardial perfusion PET/CT on patients without coronary artery disease using a time-efficient protocol, since reference values for this particular type of study are lacking in literature. In addition, we aim to determine the effect of the residual activity correction algorithm in this time-efficient protocol.ResultsA mean MBF in rest of 1.02 ± 0.22 ml/g/min, a mean MBF in stress of 2.54 ± 0.41 ml/g/min with a mean MFR of 2.60 ± 0.61 were measured. Female patients had a significant higher MBF in rest and stress, but lower MFR; a small but significant negative correlation was measured between age and MBF in stress and MFR. Residual activity correction had a significant effect resulting in a difference in global stress MBF before and after correction of 0.39 ± 0.13 ml/g/min.ConclusionsThis study established flow values for 13NH3 myocardial PET/CT with a time-efficient protocol, and established that MBF in stress corrected for residual activity is comparable with known reference values in normal studies without temporal overlap. Further validation of the technique could be of value, e.g. by comparison to standard imaging without temporal overlap, or validation against catheterization results.

Myocardial perfusion in patients with non-ischaemic systolic heart failure and type 2 diabetes: a cross-sectional study using Rubidium-82 PET/CT.

Both patients with non-ischaemic systolic heart failure and patients with type 2 diabetes (T2DM) often have reduced myocardial blood flow without significant coronary atherosclerosis. However, the mechanisms are not fully understood. The aim of this study was to investigate whether perfusion is reduced additionally when the 2 are combined. In a cross-sectional study, we scanned patients with non-ischaemic systolic heart failure with and without T2DM using Rubidium-82 positron emission tomography/computed tomography at rest and adenosine-induced stress, thereby obtaining the myocardial flow reserve (myocardial flow reserve (MFR) = stress flow/rest flow) as a measure of the myocardial vasomotor function; 28 patients with T2DM and 123 without T2DM were included. All patients received heart failure treatment according to guidelines. Multiple regression analysis was performed to assess the association between T2DM and MFR. Age [68 (60-75) years vs. 68 (62-72) years; P = 0.84] and female sex (21% vs. 33%; P = 0.26) were similar between patients with and without T2DM. Patients with T2DM had higher body mass index, (29.9 vs. 26.5kg/m2; P = 0.02), higher blood glucose (6.2 vs. 5.7mmol/L; P = 0.03), more often hypertension (50 vs. 27%; P = 0.02) and received more cholesterol lowering medication (61 vs. 35%; P = 0.02). Apart from this, the groups were similar. In a multivariable analysis, MFR was 16% lower in patients with T2DM compared with patients without [estimate - 16%; 95% confidence interval (CI) - 29 to - 0.7%; P = 0.04]. Patients with T2DM and systolic heart failure have lower myocardial flow reserve compared with heart failure patients without T2DM.

CORONARY ARTERY MICROVASCULAR DYSFUNCTION: ROLE OF SEX AND ARTERIAL LOAD

s S279 Young Investigator Award Winner e Clinical Science 528 CORONARY ARTERY MICROVASCULAR DYSFUNCTION: ROLE OF SEX AND ARTERIAL LOAD T Coutinho, L Mielniczuk, K Srivaratharajah, R deKemp, RS Beanlands

Patients with reduced heart rate response to adenosine infusion have low myocardial flow reserve in 13N-ammonia PET studies

To assess the effect of adenosine infusion by evaluating the relationship between heart rate (HR) response to adenosine and myocardial flow reserve (MFR) of remote regions supplied by normal coronary arteries in 13N-ammonia PET. Thirty-one consecutive subjects (20 known coronary artery disease patients, 4 chronic heart failure patients, and 7 normal volunteers) except cases having 3-vessel disease underwent rest and adenosine stress 13N-ammonia myocardial perfusion PET. Semi-quantitative, quantitative, and gated analyses were performed. Subjects were divided into two groups with regard to HR response to adenosine. Twenty-two subjects had normal HR response (peak/rest HR > 1.20), while reduced HR response (≤1.20) was observed in nine subjects. There were no differences in rest myocardial blood flow (MBF) of remote regions between the groups. Subjects with reduced HR response had significantly lower stress MBF and MFR of remote regions than those with normal HR response (stress MBF: 1.559 ± 0.517 vs. 2.279 ± 0.530, p = 0.004, MFR: 1.59 ± 0.36 vs. 2.35 ± 0.53, p = 0.001). There were no significant differences between the groups by means of semi-quantitative scoring. Rest and stress ejection fraction (EF) in the reduced HR response group was lower than that in the normal HR response group. In a multiple stepwise regression analysis, HR ratio, dyslipidemia, and Brinkman index were identified as predictors of the change in MFR of remote regions. Subjects with reduced HR response to adenosine had lower stress MBF and MFR of remote regions and lower EF. Moreover, HR response was one of the predictors of the change in MFR of remote regions.