Comorbidities associated with reduced myocardial flow reserve in non-obstructive disease

Abstract Introduction Microvascular Dysfunction defined as a Myocardial Flow Reserve (MFR) <2 or <2.5 depending on the center, may present in the absence of significant obstruction (1,2); it is included as a diagnosis criteria of Microvascular Angina (MVA) (3,4) and is an independent risk factor associated with poor prognosis (5–7). Traditional Coronary Artery Disease (CAD)risk factors have also been associated with MVA (8–10), however, there is reduced data in latin populations with high prevalence of comorbidities. The aim of this study was to identify the comorbidities that alter MFR with 13N-ammonia Positron Emission Tomography/Cardiac Tomography (PET/CT) and Cardiac Computed Tomography Angiography (CCTA) in a cardiovascular imaging referral center. Methods Retrospective cross-sectional study of patients with suspected CAD in which both PET/CT and CCTA were performed. Inclusion:CCTA with obstruction <50%. Exclusion: incomplete study, previous infarction or intervention. Clinical data was assessed. Mean (±DE) or median (interquartile range) to present continuous variables according to their distribution; T student or U Man Whitney to compare them. For each variable two groups were conformed depending on its presence or absence in order to compare MFR between them. Statistical analysis was performed with Statistical Package for Social Science (SPSs Inc, Chicago, IL; version 23.0) and GraphPad Prism version 9.0. p<0.05 was considered as significant. Results 335 patients included. MFR difference for each variable: female sex, hypertension (HT), Type 2 diabetes (T2D) and smoking – Appendix 1. Significant MFR difference for HT (p=0.024) and T2D (p=0.046). Severe ischemia had significant MFR reduction (p=0.006); patients with both HT and mild ischemia (p=0.018) – Appendix 2. Discussion Individuals with HT and T2D had a significantly lower MFR, consistent with previous studies (8,9). Absence of correlation with other risk factors, such as smoking (10) and female sex (11); latter may be caused by a significant lower number of women (108 vs 227). Further analysis in this subgroup ought to be done. When comparing MFR between level-of-ischemia groups, microvascular function was not reduced until severe ischemia. Remarkably, if we analyze the coexistence of HT with ischemia, MFR is reduced even in patients with mild ischemia. This finding highlights the importance of HT which alters function in early stages even in the absence of significant obstruction. This is one of the first studies correlating MFR with comorbidities in our population. Limitations the retrospective nature of the study. Conclusions MFR non-invasive assessment by PET/CT allows identifying very early stages of MVD, even in asymptomatic patients and when there's no evidence of ischemia or CAD. Therefore, timely recognition of this problem is mandatory to implement action strategies to stop the triggered events' cascade. FUNDunding Acknowledgement Type of funding sources: None.

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Clinical and imaging variables associated to Microvascular Angina, a 13N-AMMONIA MPI Approach

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeab111.064 ◽

2021 ◽

Vol 22 (Supplement_3) ◽

Author(s):

JK Rojas-Senarque ◽

H Gurrola-Luna ◽

I Carvajal-Juarez ◽

ME Soto-Lopez ◽

B Belen-Rivera ◽

...

Keyword(s):

Risk Factors ◽

Microvascular Dysfunction ◽

Wilcoxon Test ◽

Systemic Hypertension ◽

Categorical Variables ◽

Microvascular Angina ◽

Cardiac Computed Tomography Angiography ◽

Pet Ct ◽

Group B ◽

Severe Ischemia

Abstract Funding Acknowledgements Type of funding sources: None. On Behalf of MiniFellows Research Group CLINICAL AND IMAGING VARIABLES IN MICROVASCULAR ANGINA. A 13N-AMMONIA MPI APPROACH Background Patients with typical angina may have no obstructive artery disease1 and 2/3 may present microvascular dysfunction(MVD)2 which is associated with poor prognosis3,4,5. In 2017 the Coronary Vasomotion Disorders International Study Group (COVADIS) included it as a criteria of MVA6; later, included in MINOCA ESC 2020 guidelines.7 For diagnosis6,7: symptoms of ischemia; absence of relevant epicardial CAD (<50% diameter reduction or FFR >0.80); myocardial ischemia; impaired coronary microvascular function (CFR < 2 or <2.5 depending on methodology). Our aim was to identify clinical and imaging variables in patients with MVA due to 13N-ammonia Positron Emission Tomography/Cardiac Tomography(PET/CT) and Cardiac Computed Tomography Angiography(CCTA) in a cardiovascular imaging referral center. Methods.Retrospective, cross-sectional study of patients with suspected CAD. For inclusion: ischemia quantitation (summed stress score,SDS < 3) and obstruction <50% in all vessels. Exclusion criteria: previous infarction, intervention, or incomplete study. Clinical data was assessed. Both studies performed on the same day. Frequencies and percentages to report categorical variables; x2 and Fisher´s exact tests to compare them. Mean (+/-DE) or median (interquartile range) to report continuous variables according to their distribution, and T student or Wilcoxon test to compare them. Results 274 patients included: Group A (CFR <2) and group B (CFR 2)(108vs166). Difference for systemic hypertension(p <0.001), type 2 diabetes mellitus(p <0.001), dyslipidemia(p = 0.019), smoking(p <0.001). Group B presented higher incidence for mild ischemia(p = 0.004) while MVA for severe ischemia(p = 0.002). Difference between groups for EDV and ESV at rest (p = 0.002), EDV at stress(p = 0.03) and at rest(p < 0.001), LVEF at rest and stress(p < 0.001) and for a negative change of LVEF(p < 0.001). Also, reduced Calcium Score(SC)(p < 0.001) Discussion With a higher prevalence reported in women8,9, no difference for women in both groups. Presentation been reported as atypical 3,6,10, as in our study. Traditional risk factors may affect the microvascular circulation earlier in the disease. Regarding mild and severe ischemia, CFR´s may be lower in defect perfusion zones and presence of both ischemia and MVD has worse prognosis11 suggesting ischemia could had already developed in this group. LVEF drop supports the relation between CFR and ventricular function12. Finally, MVA group had a reduced CS, associated with CAD and worse prognosis, suggesting it also affects the microvasculature function. Conclusions 13N-ammonia PET/CT MPI with CCTA is a great combination to diagnose MVA, whose main component is microvascular dysfunction. Recognizing the risk factors associated with this pathology allows making opportune detections, implementing early treatment strategies, controlling symptoms and avoiding the disease"s evolution

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Survival Outcome with Routine Clinical Use of 82Rb PET/CT Myocardial Blood Flow (MBF) Quantification

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeab111.067 ◽

2021 ◽

Vol 22 (Supplement_3) ◽

Author(s):

S Wan ◽

ME Speechly-Dick ◽

LJ Menezes ◽

R Endozo ◽

R Bell ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Blood Flow ◽

Ejection Fraction ◽

Myocardial Blood Flow ◽

Univariate Analysis ◽

Myocardial Flow Reserve ◽

Flow Reserve ◽

Pet Ct ◽

Myocardial Flow

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): NIHR Biomedical Research Centre, University College London Hospitals Background The prognostic value of 82Rb PET/CT derived myocardial blood flow (MBF) is increasingly recognised in both general and specific cardiovascular populations. Purpose This study investigates the prognostic potential of MBF in a large cohort of patients undergoing routine 82Rb PET/CT examination. Methods 1148 consecutive patients (687 males, mean age 64 +/- 12 years) whom had been referred for 82Rb PET/CT examination in a single centre were included in this study. All patients completed a stress 82Rb PET/CT with adenosine infusion, paired with a rest study. Dynamic PET acquisitions were performed in both. Cardiovascular risk factors were documented as per clinical routine. Images were checked for quality and analysed using a proprietary software by an experienced operator to derive MBF parameters. Overall survival was recorded following the study. Results Median follow-up period was 71 +/- 28 months. Mean survival was 121 (95% CI: 118-124) months. On univariate analysis, global myocardial flow reserve <1.77 was associated with a higher all-cause mortality (p < 0.001). Other parameters including higher age (> =76 years), lower BMI (<21), qualitative abnormality on the myocardial perfusion scan (MPS), low hyperaemic ejection fraction on the gated studies (stress < 37 and rest < 34). Patients being on cardiac glycosides and diuretics were also significant predictor of poor prognosis (p < 0.001) on univariate analysis, presumably reflecting underlying arrhythmia and heart failure. A multivariate Cox regression analysis (step-wise Forward Wald), comprising of the above significant univariate markers, highlighted global myocardial flow reserve (HR: 2.6, 95%CI: 1.8-3.6, p < 0.001), age (HR: 2.8, 95%CI: 2.0-3.9, p < 0.001),, BMI (HR: 2.7, 95%CI: 1.7-4.1, p < 0.001),, ejection fraction (stress - HR: 3.3, 95%CI: 2.3-4.8, p < 0.001), MPS (HR: 1.5, 95%CI: 1.1-2.1, p = 0.024), and patients on diuretics (HR: 1.8, 95%CI: 1.2-2.5, p = 0.003) were independent predictors of overall survival (overall model: p < 0.001) Discussion We show that high volume routinely derived MBF in patients undergoing 82Rb PET/CT is a strong predictor of mortality and independent of other risk factors. This has important clinical implication for measuring not only interventional treatment but also measuring the effect of lifestyle and medical strategies.

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Differential association of diabetes mellitus and female sex with impaired myocardial flow reserve across the spectrum of epicardial coronary disease

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez163 ◽

2019 ◽

Vol 21 (5) ◽

pp. 576-584

Author(s):

Kai Yi Wu ◽

Nicholas P Timmerman ◽

Rachel McPhedran ◽

Alomgir Hossain ◽

Rob S B Beanlands ◽

...

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Multiple Linear Regression Model ◽

Myocardial Flow Reserve ◽

Additional Patient ◽

Rate Pressure Product ◽

Female Sex ◽

Flow Reserve ◽

Imaging Results ◽

Myocardial Flow

Abstract Aims Diabetes mellitus (DM) affects the macro- and microvasculature, leading to impairment in coronary vascular reactivity. Microvascular dysfunction is more prevalent in females compared to males, leading to increased cardiovascular risk in women. The purpose of this study was to quantify the association between diabetes and female sex on myocardial flow reserve (MFR) across the spectrum of epicardial coronary artery disease (CAD). Methods and results In 222 patients with known or suspected CAD (63.7 ± 10.7 years, 66 females, 85 with diabetes) who had rubidium-82 positron emission tomography (PET) and invasive coronary angiography within 6 months, a multiple linear regression model was developed to predict MFR based on clinical risk factors and imaging results across a spectrum of regional epicardial disease. A significant interaction effect suggested that impairment of MFR is accelerated in diabetics with increasing severity of epicardial disease. Furthermore, female sex (−13%), decade of age (−6%), ischaemia on electrocardiogram (−10%), resting rate-pressure product (−3%), and rest end-diastolic volume (−0.2%) were associated with reductions in MFR independent of the combined extent and severity of epicardial disease. Conclusion In the presence of significant obstructive epicardial disease, MFR decreases more rapidly in patients with DM compared to those without. Additional patient demographics and risk factors such as female sex and older age, and stress PET functional parameters should also be considered in the clinical interpretation of MFR. This has implications for the diagnosis and management of CAD patients with these and other risk factors for microvascular disease.

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Impaired Myocardial Flow Reserve on 82Rubidium Positron Emission Computed Tomography in Patients with Systemic Sclerosis

The Journal of Rheumatology ◽

10.3899/jrheum.210040 ◽

2021 ◽

pp. jrheum.210040

Author(s):

Attila Feher ◽

Nabil E. Boutagy ◽

Evangelos K. Oikonomou ◽

Stephanie Thorn ◽

Yi-Hwa Liu ◽

...

Keyword(s):

Computed Tomography ◽

Systemic Sclerosis ◽

Myocardial Flow Reserve ◽

Coronary Microvascular Dysfunction ◽

Emission Computed Tomography ◽

Flow Reserve ◽

Positron Emission ◽

Pet Ct ◽

Myocardial Flow ◽

Healthy Participants

Objective To investigate the association between Raynaud phenomenon (RP) and coronary microvascular dysfunction, we measured myocardial flow reserve (MFR) using positron emission tomography/computed tomography (PET/CT) in primary and secondary RP patients and controls. Methods RP patients, patient controls and healthy participants who underwent dynamic reststress 82-Rubidium PET/CT were studied. Differences in heart rate-blood pressure product corrected MFR and clinical predictors of reduced MFR (< 2.0) were determined. Results 49 RP patients (80% female, 65 ± 11 years): 11 primary RP, 18 systemic sclerosis (SSc) and 20 other autoimmune diseases (AID) (n=6 systemic lupus erythematosus, n=6 rheumatoid arthritis, n=4 overlap syndrome, n=2 Sjogren's syndrome, n=2 inflammatory arthritis), 49 matched patients without RP or AID (78% female, 64 ± 13 years) and 14 healthy participants (50% female, 35 ± 5 years) were studied. Primary RP patients, matched patient controls and healthy participants had comparable MFR. SSc-RP patients had significantly reduced MFR (1.62 ± 0.32) compared to matched patient controls (p=0.03, 2.06 ± 0.61) and to healthy participants (p=0.01, 2.22 ± 0.44). In multivariable logistic regression, SSc was an independent predictor of reduced MFR. We identified a correlation between time since AID diagnosis and MFR (r= -0.37; 95% CI: -0.61 to -0.09; p=0.01). Conclusion Our findings suggest that only secondary, not primary, RP is associated with reduced MFR, and that SSc-RP patients have reduced MFR compared to primary RP and other

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

Journal of Hypertension ◽

10.1097/01.hjh.0000548594.65034.48 ◽

2018 ◽

Vol 36 ◽

pp. e147

Author(s):

Tine Hansen ◽

Emilie H. Zobel ◽

Signe A. Winther ◽

Philip Hasbak ◽

Bernt J. von Scholten J. von Scholten ◽

...

Keyword(s):

Type 1 Diabetes ◽

Myocardial Flow Reserve ◽

Albumin Excretion ◽

Flow Reserve ◽

Pet Ct ◽

Myocardial Flow

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Comparison of the Prognostic Value of Global and Regional Myocardial Flow Capacity Radius, Myocardial Flow Reserve, and Stress Myocardial Blood Flow Using Rubidium-82 with SiPM PET/CT

10.21203/rs.3.rs-1122028/v1 ◽

2021 ◽

Author(s):

Matthieu DIETZ ◽

Christel H Kamani ◽

Gilles Allenbach ◽

Vladimir Rubimbura ◽

Stephane Fournier ◽

...

Keyword(s):

Blood Flow ◽

Myocardial Blood Flow ◽

Myocardial Flow Reserve ◽

Flow Capacity ◽

Flow Reserve ◽

Stress Myocardial Blood Flow ◽

Pet Ct ◽

Myocardial Flow ◽

Rubidium 82 ◽

Regional Myocardial Flow

Abstract Purpose The aim of this study was to assess the most reliable quantitative variable on Rubidium-82 (82Rb) cardiac PET/CT for predicting major adverse cardiovascular events (MACE), on the latest PET camera using silicon photomultipliers digital readout (SiPM) technology. Methods We prospectively enrolled 274 consecutive participants with suspected myocardial ischemia. Participants underwent 82Rb cardiac SiPM PET/CT and were followed-up for MACE over 652 days (interquartile range: 559 to 751 days). For each participant, global and regional myocardial flow reserve (MFR), stress myocardial blood flow (stress MBF) and their combination as myocardial flow capacity radius (MFC radius) were measured. Results On receiver operator curve analysis, MACE prediction was similar for global and regional MFR, stress MBF, and MFC radius (area under the curve; (i) Global: 0.70 vs. 0.71 and 0.73, and (ii) Regional: 0.71 vs. 0.71 and 0.73, respectively, p > 0.1 for all pairwise comparisons). On multivariable analysis, (i) Global: MFR < 1.98, stress MBF < 1.94 mL/g/min, and MFC radius < 3.12, as well as (ii) Regional: MFR < 1.75, stress MBF < 1.75 mL/g/min, and MFC radius < 2.7, emerged all as similar independent predictors of MACE (p < 0.001 for all). Conclusions Using the latest SiPM PET technology with 82Rb, global and regional MFR, stress MBF, and MFC radius are similar powerful predictors of cardiovascular event.

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