Myocardial Perfusion Reserve Index Research Articles

Arterial stiffness assessment in coronary microvascular dysfunction and heart failure with preserved ejection fraction: An initial report from the WISE-CVD continuation study

BackgroundHeart failure with preserved ejection fraction (HFpEF) is the most common cardiac complication in patients with coronary microvascular dysfunction (CMD), yet its underlying pathways remain unclear. Aortic pulse-wave velocity (aPWV) is an indicator of large artery stiffness and a predictor for cardiovascular disease. However, aPWV in CMD and HFpEF is not well characterized and may provide understanding of disease progression. MethodsAmong participants without obstructive coronary artery disease, we evaluated 51 women with suspected CMD and 20 women and men with evidence of HFpEF. All participants underwent aPWV measurement (SphygmoCor, Atcor Medical) with higher aPWV indicating greater vascular stiffness. Cardiac magnetic resonance imaging (CMRI) assessed left ventricular (LV) ejection fraction, CMD via myocardial perfusion reserve index (MPRI), and ventricular remodeling via LV mass-volume ratio. . Statistical analysis was performed using Wilcoxon rank sum tests, Pearson correlations and linear regression analysis. ResultsCompared to the suspected CMD group, the HFpEF participants were older (65 ± 12 vs 56 ± 11 yrs., p = 0.002) had higher BMI (31.0 ± 4.3 vs 27.8 ± 6.7 kg/m2, p = 0.013), higher aPWV (10.5 ± 2.0 vs 8.0 ± 1.6 m/s, p = 0.05) and lower MPRI (1.5 ± 0.3 vs1.8 ± 0.3, p = 0.02), but not remodeling. In a model adjusted for cardiovascular risk factors, the HFpEF group had a lower LVEF (estimate −4.78, p = 0.0437) than the suspected CMD group. ConclusionsHFpEF participants exhibit greater arterial stiffness and lower myocardial perfusion reserve, with lower LVEF albeit not remodeling, compared to suspected CMD participants. These findings suggest arterial stiffness may contribute to progression from CMD to HFpEF. Prospective work is needed and ongoing.

Coronary microvascular dysfunction: prevalence and aetiology in patients with suspected myocardial ischaemia

To evaluate the prevalence, aetiology, and corresponding morbidity of coronary microvascular dysfunction (CMD) in patients with suspected myocardial ischaemia. The present study included 115 patients with suspected myocardial ischaemia who underwent stress perfusion cardiac magnetic resonance imaging. CMD was assessed visually based on the myocardial perfusion results. The CMR-derived myocardial perfusion reserve index (MPRI) and left ventricular (LV) strain parameters obtained using the post-processing software CVI42 were employed to evaluate LV myocardial perfusion and deformation. LV strain parameters included global longitudinal, circumferential, and radial strain (GLS, GCS, and GRS), global systolic/diastolic longitudinal, circumferential, and radial strain rates (SLSR, SCSR, SRSR, DLSR, DCSR, and DRSR). Of the 115 patients, 12 patients were excluded and 103 patients were finally included in the study. CMD was observed in 79 % (81 patients, aged 53±12 years) of patients. Regarding aetiology, 91 (88 %) patients had non-obstructive coronary artery disease (CAD), eight (8 %) had obstructive CAD, and four (4 %) had hypertrophic cardiomyopathy (HCM). The incidence of CMD was highest (100 %) in patients with HCM, followed by those with non-obstructive CAD (up to 79 %). There were no statistical differences between CMD and non-CMD groups in GCS, GRS, GLS, SRSR, SCSR, SLSR, DCSR, DRSR and DLSR. The incidence of CMD was higher in patients with signs and symptoms of ischaemia. CMD occurred with non-obstructive CAD, obstructive CAD, and HCM, with the highest prevalence of CMD in HCM.

Early left ventricular microvascular dysfunction in diabetic pigs: a longitudinal quantitative myocardial perfusion CMR study

BackgroundMicrovascular pathology is one of the main characteristics of diabetic cardiomyopathy; however, the early longitudinal course of diabetic microvascular dysfunction remains uncertain. This study aimed to investigate the early dynamic changes in left ventricular (LV) microvascular function in diabetic pig model using the cardiac magnetic resonance (CMR)-derived quantitative perfusion technique.MethodsTwelve pigs with streptozotocin-induced diabetes mellitus (DM) were included in this study, and longitudinal CMR scanning was performed before and 2, 6, 10, and 16 months after diabetic modeling. CMR-derived semiquantitative parameters (upslope, maximal signal intensity, perfusion index, and myocardial perfusion reserve index [MPRI]) and fully quantitative perfusion parameters (myocardial blood flow [MBF] and myocardial perfusion reserve [MPR]) were analyzed to evaluate longitudinal changes in LV myocardial microvascular function. Pearson correlation was used to analyze the relationship between LV structure and function and myocardial perfusion function.ResultsWith the progression of DM duration, the upslope at rest showed a gradually increasing trend (P = 0.029); however, the upslope at stress and MBF did not change significantly (P > 0.05). Regarding perfusion reserve function, both MPRI and MPR showed a decreasing trend with the progression of disease duration (MPRI, P = 0.001; MPR, P = 0.042), with high consistency (r = 0.551, P < 0.001). Furthermore, LV MPR is moderately associated with LV longitudinal strain (r = − 0.353, P = 0.022), LV remodeling index (r = − 0.312, P = 0.033), fasting blood glucose (r = − 0.313, P = 0.043), and HbA1c (r = − 0.309, P = 0.046). Microscopically, pathological results showed that collagen volume fraction increased gradually, whereas no significant decrease in microvascular density was observed with the progression of DM duration.ConclusionsMyocardial microvascular reserve function decreased gradually in the early stage of DM, which is related to both structural (but not reduced microvascular density) and functional abnormalities of microvessels, and is associated with increased blood glucose, reduced LV deformation, and myocardial remodeling.

Automatic calculation of myocardial perfusion reserve using deep learning with uncertainty quantification.

Myocardial perfusion reserve index (MPRI) in magnetic resonance imaging (MRI) is an important indicator of ischemia, and its measurement typically involves manual procedures. The purposes of this study were to develop a fully automatic method for estimating the MPRI and to evaluate its performance. The method consisted of segmenting the myocardium in dynamic contrast-enhanced (DCE) myocardial perfusion MRI data using Monte Carlo dropout U-Net, dividing the myocardium into segments based on landmark localization with machine learning, and estimating the MPRI after the calculation of the left ventricular and myocardial contrast upslopes. The proposed method was compared with a reference method, which involved manual adjustments of the myocardial contours and upslope ranges. In test subjects, MPRIs measured by the proposed technique correlated with those by the manual reference in segmental assessment [intraclass correlation coefficient (ICC) =0.75, 95% CI: 0.70-0.79, P<0.001]. The automatic and reference MPRI values showed a mean difference of -0.02 and 95% limits of agreement of (-0.86, 0.82). The proposed automatic method is based on deep learning segmentation and machine learning landmark detection for MPRI measurements in DCE perfusion MRI. It holds the potential to efficiently and quantitatively assess myocardial ischemia without any user's interaction.

Developing and evaluating a chronic ischemic cardiomyopathy in swine model by rest and stress CMR.

A large animal model of chronic coronary artery disease (CAD) is crucial for the understanding the underlying pathophysiological processes of chronic CAD and consequences for cardiac structure and function. The goal of this study was to develop a chronic model of CAD in a swine model and to evaluate the changes of myocardial structure, myocardial motility, and myocardial viability during coronary stenosis. A total of 30 swine (including 24 experimental animals and 6 controls) were enrolled. The chronic ischemia model was constructed by using Ameroid constrictor in experimental group. The 24 experimental animals were further divided into 4 groups (6 animals in each group) and were sacrificed at 1, 2, 3 and 4 weeks after operation for pathological examination, respectively. Cardiac magnetic resonance (CMR) was performed preoperatively and weekly postoperatively until sacrificed both in experimental and control group. CMR cine images, rest/adenosine triphosphate (ATP) stress myocardial contrast perfusion and LGE were performed and analyzed. The rest wall thickening (WT) score was calculated from rest cine images. The MPRI (myocardial perfusion reserve index) and MPR (myocardial perfusion reserve) were calculated based on rest and stress perfusion images. Pathology staining including triphenyltetrazolium chloride, HE and picrosirus red staining were performed after swine were sacrificed and collagen volume fraction (CVF) was calculated. The time to formation of ischemic, hibernating, and infarcted myocardium was recorded. In experimental group, from 1w to 4w after surgery, the rest WT score decreased gradually from 35.2 ± 2.0%, 32.0 ± 2.9% to 30.5 ± 3.0% and finally 29.06 ± 1.78%, p < 0.001. Left ventricular ejection fraction was gradually impaired after modeling (58.9 ± 12.6%, 56.3 ± 10.1%, 55.3 ± 9.0%, 53.8 ± 9.9%, respectively). And the MPR and MPRI also decreased stepwise with extent of surgery time (MPRI dropped from 2.1 ± 0.4, 2.0 ± 0.2 to 1.8 ± 0.3 and finally 1.7 ± 0.1, p = 0.004; MPR dropped from 2.3 ± 0.4, 2.1 ± 0.2 to 1.9 ± 0.4 and finally 1.8 ± 0.1, p < 0.001). Stronger associations between MPR, MPRI and CVF were paralleled lower wall thickening scores in fibrosis-affected areas. The ischemic myocardium was first appeared in the first week after surgery (involving ten segments), hibernated myocardium was first appeared in the second week after surgery (involving seventeen segments). LGE was first appeared in eight swine in the third weeks after surgery (16 segments). At 4w after surgery, average 9.6g scar tissue was found among 6 swine. At the same time, histological analysis established the presence of fibrosis and ongoing apoptosis in the infarcted area. In conclusion, our study provided valuable insights into the pathophysiological processes of chronic CAD and its consequences for cardiac structure and function in a large animal model through combining myocardial motion and stress perfusion.

Ventricular arterial coupling in patients with ischemia but no obstructive coronary artery disease: novel insight into heart failure progression

Abstract Background Ischemia with no obstructive coronary artery disease (INOCA) is prevalent in women and is associated with increased risk of developing heart failure with preserved ejection fraction (HFpEF). While the exact mechanism contributing to heart failure progression remains incompletely understood, we hypothesize that impaired ventricular-arterial coupling (VAC) plays a key role. Purpose To evaluate VAC across the INOCA-HFpEF continuum. Methods To accomplish our research objective, we leveraged cardiac magnetic resonance images from individuals with INOCA and HFpEF from the WISE Pre-HFpEF (NCT03876223) and WISE HFpEF (NCT02582021) studies, along with reference controls. Aortic pulse wave velocity (aPWV) was measured using velocity-encoded MRI, from the proximal ascending to distal descending aorta. Global longitudinal strain (GLS) was measured by feature tracking of horizontal and vertical long axis cine images. VAC was defined as the ratio between aPWV and GLS. To test for potential mediators, we assessed the relationship between VAC and age, risk factors, systolic blood pressure (SBP), diastolic blood pressure (DBP), myocardial perfusion reserve index (MPRI), LV end diastolic pressure (LVEDP), cardiac structure/function, and Kansas City Cardiomyopathy questionnaire (KCCQ). Results The baseline characteristics of the three study groups are described in the Table. Patients with INOCA had similar KCCQ scores as HFpEF patients, suggesting INOCA patients may have subclinical HFpEF. Consistent with our hypothesis, we observed a progressive impairment in VAC across the three groups (Controls vs INOCA vs HFpEF), being significantly worst in HFpEF(Figure). Importantly, VAC was inversely related with age, systolic/diastolic blood pressure, and LV mass index (R=-0.6, R=-0.4, R=-0.4, R=-0.3 respectively, all p &amp;lt;0.001). Conclusion The data herein support the hypothesis that VAC contributes to heart failure progression, with age, arterial blood pressure and LV mass being key determinants. That VAC was not yet significantly different between INOCA, and reference controls highlights an important opportunity for intervention to prevent heart failure progression.

Improvement in myocardial energetics and perfusion with Liraglutide in patients with type 2 diabetes- A randomised, single centre, open label, cross-over drug trial

Abstract Background Both the insulin secretion and insulin resistance in Type 2 diabetes (T2D) are amenable to pharmacological intervention. In a single center, open-label, randomized, cross-over design trial we sought to compare two distinct glycaemic control strategies of targeting beta-cell dysfunction and promoting insulin secretion using Glucagon-like peptide-1 receptor agonists (GLP-1RA) -liraglutide and targeting peripheral insulin resistance using a peroxisome proliferator activated receptor-gamma agonist (PPAR-g)-pioglitazone to see which results in greater improvements in myocardial perfusion, energetics and function in patients with T2D. Methods Fifty-two T2D patients were screened. Eligible patients with no known prior cardiovascular disease were randomized in a 1:1 ratio to be administered one of the study drugs for a 16-week treatment period followed by an 8-week washout and a further 16-week treatment period for the second drug. Thirty-three eligible participants completed both treatment periods. Participants have undergone 31phosphorus magnetic resonance spectroscopy (31P-MRS) at rest and dobutamine stress followed by the cardiac magnetic resonance (CMR) scans. The CMR protocol consisted of rest and dobutamine stress cine imaging, perfusion imaging (motion corrected, automated in-line perfusion mapping), velocity-encoded mitral in-flow imaging and late gadolinium enhanced imaging at 3T immediately before commencement and after completion of each treatment arm (four scans per participant). Results Clinical and biochemical characteristics, and CMR/31P-MRS results are provided in Tables 1&amp;2 respectively. Liraglutide therapy resulted in a significant reductions in the body mass index and significant improvements in glycemic control. Both drugs reduced insulin resistance indicated by a reduction in the mean triglyceride index. There were no significant changes in NTproBNP or troponin levels with either drug. Therapy with either drug did not result in a significant change in the LV end-diastolic volume, ejection fraction or global longitudinal shortening. Pioglitazone led to a significant increment in mean LV mass and LV mass index, while no significant effect in myocardial mass or mass index were detected with liraglutide. Liraglutide therapy resulted in increased rest and dobutamine stress energetics, global stress myocardial blood flow and myocardial perfusion reserve index. While pioglitazone treatment showed no significant effect in these parameters, an isolated improvement in the rest diastolic function was detected in this arm. Conclusions In this randomised cross-over design trial we showed for the first time that four months treatment with glucagon like protein 1 receptor agonist liraglutide results in significant improvements in myocardial stress perfusion and energetics. Pioglitazone results in an isolated improvement in rest diastolic funct

The left main coronary artery (LMCA) physiology study: comprehensive clinical haemodynamic evaluation of physiology and pathophysiology

Abstract Background &amp; Purpose At present, physiological evaluation of left main coronary artery (LMCA) disease is based on the assumption that pressure-based indices are agnostic to the vessel being assessed. We conducted mechanistic studies to determine whether pressure-based indices in the left anterior descending (LAD) and left circumflex (LCx) arteries are different and if so, the basis of this discrepancy, in patients with normal coronary arteries (LMCA Physiology Study) and in those with isolated LMCA disease (LMCA Pathophysiology Study). Methods Patients with exertional angina were prospectively enrolled after baseline investigation of computed tomography or invasive angiography and those with left ventricular impairment were excluded. Eligibility for the Physiology Study required the absence of epicardial disease on angiography and/or fractional flow reserve or significant coronary microvascular disease (LAD coronary flow reserve (CFR) &amp;lt;2.0). Simultaneous intracoronary pressure and Doppler measurements were performed in the LAD and LCx arteries, at rest and adenosine mediated hyperaemia. A subset also underwent 3-Tesla quantitative stress perfusion cardiac magnetic resonance imaging. Eligibility for the Pathophysiology Study required isolated LMCA disease, which was verified physiologically by pressure wire pullback according to predefined criteria of 1) ≥80% of total FFR arising from the left main coronary artery disease and 2) ≤0.05 FFR gradient distal to the left main coronary artery disease in both vessels. A paired 2-tailed test for significance was performed for all analyses. The protocols were approved by the UK National research ethics committee. Results 71 patients were prospectively enrolled, 28 in the Physiology Study and 43 in the Pathophysiology Study (Table 1). In the LMCA Physiology Study, CFR was higher and hyperaemic microvascular resistance (hMR) lower in the LAD compared to the LCx. In the LMCA Pathophysiology Study, the contribution to total FFR of downstream disease was negligible and comparable in both branches. Moreover, hyperaemic, and non-hyperaemic pressure-based indices were all significantly lower in the LAD, compared to the LCx. In addition, CFR was higher and hMR lower in the LAD compared to the LCx. Correlations are outlined in Figure 1. Differences in pressure-derived measurements remained after correction for the influence of hydrostatic pressures. However, when adjusted for subtended myocardial mass, there was no significant difference in invasive hemodynamic indices or quantitative perfusion analysis-derived myocardial perfusion reserve index. Conclusions Commonly used indices of stenosis severity are not agnostic to the vessel assessed due to differences in myocardial mass and microvascular resistances. The need for vessel-specific thresholds has significant implications on LMCA disease assessment and potentially, interpretation of the existing evidence base on physiological assessment of non-LMCA disease.Table 1Figure 1

Abstract 18068: Isometric Handgrip Exercise Myocardial Perfusion Reserve Correlates With Coronary Microvascular Dysfunction and Abnormal Left Ventricular Strain: A Report From the Women’s Ischemia Syndrome Evaluation Pre-Heart Failure With Preserved Ejection Fraction Study

Background: Impaired coronary artery response to isometric handgrip exercise (IHE) has previously been demonstrated to reflect endothelial dysfunction, an important contributor to ischemia with no obstructive coronary arteries (INOCA) and coronary microvascular dysfunction (CMD). Stress perfusion cardiac magnetic resonance (CMR) imaging is typically performed with pharmacologic stress using myocardial perfusion reserve index (MPRI) as a measure of CMD. IHE-MPRI has not been comprehensively studied in patients with INOCA, who are at risk for heart failure with preserved ejection fraction (HFpEF). Hypothesis: IHE-MPRI is related to CMD measured by pharm-MPRI and left ventricular (LV) structural and functional abnormalities in INOCA patients at risk for HFpEF. Methods: Participants with INOCA underwent comprehensive CMR with first-pass perfusion with adenosine or regadenoson, rest, and IHE. MPRI was adjusted to rest rate-pressure product (RPP). Lack of a satisfactory IHE response (defined as increase in heart rate≥10 bpm or systolic blood pressure ≥10 mmHg) was excluded. CMR measures of LV structure, function, MPRI, T1 and T2 mapping were analyzed using commercial software, blinded to clinical data. Pearson correlations were performed. Results: Of the participants (n=44) with IHE-MPRI, mean age was 55±11 years, body mass index 27±7 kg/m 2 , and 98% female, 31% hypertension, 12.5% diabetes, 19% hyperlipidemia. IHE-MPRI adjusted for rest RPP significantly correlated positively with pharm-MPRI and inversely with time to peak strain, diastolic strain measures and myocardial T2 ( Figure ). IHE-MPRI was not related to resting or IHE heart rate, systolic strain, LV mass, volumes, mass-volume ratio, native T1 or extracellular volume. Conclusion: IHE-MPRI relates to CMD and LV strain among patients with INOCA. Measurement of IHE-MPRI may improve understanding of CMD and LV structural and functional abnormalities that may contribute to development of HFpEF.

Abstract 14155: Handgrip Exercise Provoked High Sensitivity Cardiac Troponin I Increase in Women With No Obstructive Coronary Artery Disease: Relations to Myocardial Function

Background: Among women with signs and symptoms of ischemia and no obstructive coronary arteries (INOCA) around 10% develop heart failure with preserved ejection fraction (HFpEF). Mechanisms contributing to AMI and HFpEF progression in INOCA are poorly understood. Purpose: To characterize clinical profile and stress cardiac magnetic resonance imaging (CMRI) myocardial features of INOCA patients with and without increased troponin levels in response to handgrip exercise. Methods: Women with suspected INOCA underwent cardiac MRI and invasive coronary function testing (CFT), including coronary sinus (CS) cannulation, handgrip exercise testing, and serial CS plasma sampling before, after 3 minutes of isometric handgrip stress at 30% of maximal voluntary contraction, and after 5 minutes of recovery. High sensitivity cardiac troponin I (hsTnI) was measured using commercial immunoassay (R-PLEX, Meso Scale Discovery, Rockville, MD) and compared using t-tests. Results: A total of 51 women with complete data were included, of whom 31 (60.7%) had handgrip provoked increases in hsTnI levels from baseline, while 20 (39.2%) did not. Baseline characteristics are shown in Table. Patients with increased hsTnI levels had greater impaired global longitudinal strain rates and early diastolic strain rates (radial and circumferential) compared to those without increased hsTnI. No significant differences were observed in myocardial perfusion reserve index (MPRI). Conclusion: Women with INOCA demonstrating objective evidence of handgrip exercise provoked myocardial injury exhibit evidence of myocardial dysfunction not related to myocardial perfusion. Further prospective research is needed to understand the sequence of relations between coronary microvascular dysfunction contribution to HFpEF progression.

Type 2 diabetes mellitus and coronary artery disease: features of perfusion volume computed tomography of the heart in a pharmacological test with adenosine triphosphate

To study myocardial perfusion in patients with coronary artery disease (CAD) with and without type 2 diabetes mellitus (DM) using volumetric computed tomography (VCT) of the heart with a pharmacological test with adenosine triphosphate (ATP). The study included 93 patients, of which 18 had CAD with DM, and 50 had CAD without DM. All patients underwent one of the stress tests, cardiac VCT with ATP test, invasive coronary angiography, or CT coronary angiography. Left ventricle (LV) myocardial perfusion was evaluated for hypoperfusion zones and the calculation of semi-quantitative indices: decrease of LV myocardial density, LV myocardial perfusion index, transmural perfusion coefficient, and our proposed new indicator - myocardial perfusion reserve (MPR). The MPR index value in the hypoperfusion zones in patients with CAD and DM was 0.64 [0.62-0.66], in patients with CAD without diabetes 0.65 [0.63-0.66]; p=0.4; the value of the transmural perfusion coefficient in the areas of abnormal LV myocardial perfusion in patients with CAD and DM was 0.81 [0.80-0.86] versus 0.83 [0.80-0.85] in patients with CAD without DM (p=0.6). More hypoperfusion segments were observed in patients with CAD and DM (33.3%) compared to those without DM (14%; p=0.029). The MPR index in the hypoperfusion zones in patients with CAD with intact coronary arteries (CA) and DM was 0.56 [0.54-0.60] versus 0.55 [0.54-0.62] in patients with CAD with intact CA without DM; p=0.2. In patients with CAD and type 2 DM, according to the VCT with ATP test, more foci hypoperfusion areas were detected, regardless of the severity of coronary artery involvement, compared with patients with CAD without DM, which may be due to the microangiopathy in the myocardium. The similarity of the MPR parameters in the hypoperfusion zones associated with hemodynamic stenosis of the CA and with intact CAs indicates the ischemic genesis of these zones. For citation: Soboleva GN, Minasyan AA, Gaman SA, Rogoza AN, Molina LP, Soboleva TV, Shariya MA, Ternovoy SK, Karpov YuA. Type 2 diabetes mellitus and coronary artery disease: features of perfusion volume computed tomography of the heart in a pharmacological test with adenosine triphosphate. Terapevticheskii Arkhiv (Ter. Arkh.). 2023;95(4):309-315. DOI: 10.26442/00403660.2023.04.202158.

Autoimmune rheumatic diseases in women with coronary microvascular dysfunction: a report from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) project.

While autoimmune rheumatic diseases (ARDs) have been linked with coronary microvascular dysfunction (CMD), the relationship between ARD and CMD in women with signs and symptoms of ischemia and no obstructive arteries (INOCA) are not well described. We hypothesized that among women with CMD, those with ARD history have greater angina, functional limitations, and myocardial perfusion compromise compared to those without ARD history. Women with INOCA and confirmed CMD by invasive coronary function testing were included from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) project (NCT00832702). Seattle Angina Questionnaire (SAQ), Duke Activity Status Index (DASI), and cardiac magnetic resonance myocardial perfusion reserve index (MPRI) were collected at baseline. Chart review was performed to confirm self-reported ARD diagnosis. Of the 207 women with CMD, 19 (9%) had a confirmed history of ARD. Compared to those without ARD, women with ARD were younger (p = 0.04). In addition, they had lower DASI-estimated metabolic equivalents (p = 0.03) and lower MPRI (p = 0.008) but similar SAQ scores. There was a trend towards increased nocturnal angina and stress-induced angina in those with ARD (p = 0.05 for both). Invasive coronary function variables were not significantly different between groups. Among women with CMD, women with a history of ARD had lower functional status and worse myocardial perfusion reserve compared to women without ARD. Angina-related health status and invasive coronary function were not significantly different between groups. Further studies are warranted to understand mechanisms contributing to CMD among women with ARDs with INOCA.

Sex differences in contributors to coronary microvascular dysfunction.

Coronary microvascular dysfunction (CMD) has differences in prevalence and presentation between women and men; however, we have limited understanding about underlying contributors to sex differences in CMD. Myocardial perfusion reserve index (MPRI), as semi-quantitative measure of myocardial perfusion derived from cardiac magnetic resonance (CMR) imaging has been validated as a measure of CMD. We sought to understand the sex differences in the relations between the MPRI and traditional measures of cardiovascular disease by CMR. A retrospective analysis of a single-center cohort of patients receiving clinical stress CMR from 2015 to 2022 was performed. Patients with calculated MPRI and no visible perfusion defects consistent with obstructive epicardial coronary disease were included. We compared associations between MPRI versus traditional cardiovascular risk factors and markers of cardiac structure/function in sex-stratified populations using univariable and multivariable regression models. A total of 229 patients [193 female, 36 male, median age 57 (47-67) years] were included in the analysis. In the female population, no traditional cardiovascular risk factors were associated with MPRI, whereas in the male population, diabetes (β: -0.80, p = 0.03) and hyperlipidemia (β: -0.76, p = 0.006) were both associated with reduced MPRI in multivariable models. Multivariable models revealed significant associations between reduced MPRI and increased ascending aortic diameter (β: -0.42, p = 0.005) and T1 times (β: -0.0056, p = 0.03) in the male population, and increased T1 times (β: -0.0037, p = 0.006) and LVMI (β: -0.022, p = 0.0003) in the female population. The findings suggest different underlying pathophysiology of CMD in men versus women, with lower MPRI in male patients fitting a more "traditional" atherosclerotic profile.

Stress CMR T1-mapping technique for assessment of coronary microvascular dysfunction in a rabbit model of type II diabetes mellitus: Validation against histopathologic changes.

Coronary microvascular dysfunction (CMD) is an early character of type 2 diabetes mellitus (T2DM), and is indicative of adverse events. The present study aimed to validate the performance of the stress T1 mapping technique on cardiac magnetic resonance (CMR) for identifying CMD from a histopathologic perspective and to establish the time course of CMD-related parameters in a rabbit model of T2DM. New Zealand white rabbits (n = 30) were randomly divided into a control (n = 8), T2DM 5-week (n = 6), T2DM 10-week (n = 9), and T2DM 15-week (n = 7) groups. The CMR protocol included rest and adenosine triphosphate (ATP) stress T1-mapping imaging using the 5b(20b)3b-modified look-locker inversion-recovery (MOLLI) schema to quantify stress T1 response (stress ΔT1), and first-pass perfusion CMR to quantify myocardial perfusion reserve index (MPRI). After the CMR imaging, myocardial tissue was subjected to hematoxylin-eosin staining to evaluate pathological changes, Masson trichrome staining to measure collagen volume fraction (CVF), and CD31 staining to measure microvascular density (MVD). The associations between CMR parameters and pathological findings were determined using Pearson correlation analysis. The stress ΔT1 values were 6.21 ± 0.59%, 4.88 ± 0.49%, 3.80 ± 0.40%, and 3.06 ± 0.54% in the control, T2DM 5-week, 10-week, and 15-week groups, respectively (p < 0.001) and were progressively weakened with longer duration of T2DM. Furthermore, a significant correlation was demonstrated between the stress ΔT1 vs. CVF and MVD (r = -0.562 and 0.886, respectively; p < 0.001). The stress T1 response correlated well with the histopathologic measures in T2DM rabbits, indicating that it may serve as a sensitive CMD-related indicator in early T2DM.

Reduced Left Ventricular Function on Cardiac MRI in SLE Patients Correlates with Measures of SLE Disease Activity and Inflammation.

Women with SLE have an elevated risk of CVD morbidity and mortality and frequently report chest pain in the absence of obstructive CAD. Echocardiographic studies often demonstrate reduced LV function, correlating with higher disease activity. We used cardiac MRI (cMRI) to investigate the relationship between SLE, related inflammatory biomarkers and cardiac function in female SLE patients. Women with SLE reporting chest pain with no obstructive CAD (n=13) and reference controls (n=22) were evaluated using stress-rest cMRI to measure LV structure, function, tissue characteristics, and myocardial perfusion reserve index (MPRI). Coronary microvascular dysfunction (CMD) was defined as MPRI <1.84. Serum samples were analyzed for inflammatory markers. Relationships between clinical and cMRI values of SLE subjects were assessed, and groups were compared. 40% of SLE subjects had MPRI < 1.84 on cMRI. Compared to controls, SLE subjects had higher LV volumes and mass and lower LV systolic function. SLICC DI was related to worse cardiac function and higher T1. CRP was related to higher cardiac output and a trend to better systolic function, while ESR and fasting insulin were related to lower LV mass. Lower fasting insulin levels correlated with increased ECV. Among our female SLE cohort, 40% had CMD, and SLICC DI correlated with worse cardiac function and diffuse fibrosis. Higher inflammatory markers and low insulin levels may associate with LV dysfunction. Our findings underline the potential of non-invasive cMRI as a tool for monitoring cardiovascular function in SLE patients.

Impairment in quantitative microvascular function in non-ischemic cardiomyopathy as demonstrated using cardiovascular magnetic resonance

Microvascular dysfunction (MVD) is present in various cardiovascular diseases and portends worse outcomes. We assessed the prevalence of MVD in patients with non-ischemic cardiomyopathy (NICM) as compared to subjects with preserved ejection fraction (EF) using stress cardiovascular magnetic resonance (CMR). We retrospectively studied consecutive patients with NICM and 58 subjects with preserved left ventricular (LV) EF who underwent stress CMR between 2011-2016. MVD was defined visually as presence of a subendocardial perfusion defect and semiquantitatively by myocardial perfusion reserve index (MPRI<1.51). MPRI was compared between groups using univariate analysis and multivariable linear regression. In total, 41 patients with NICM (mean age 51 ± 14, 59% male) and 58 subjects with preserved LVEF (mean age 51 ± 13, 31% male) were identified. In the NICM group, MVD was present in 23 (56%) and 11 (27%) by semiquantitative and visual evaluation respectively. Compared to those with preserved LVEF, NICM patients had lower rest slope (3.9 vs 4.9, p = 0.05) and stress perfusion slope (8.8 vs 11.7, p<0.001), and MPRI (1.41 vs 1.74, p = 0.02). MPRI remained associated with NICM after controlling for age, gender, hypertension, ethnicity, diabetes, and late gadolinium enhancement (log MPR, β coefficient = -0.19, p = 0.007). MVD-as assessed using CMR-is highly prevalent in NICM as compared to subjects with preserved LVEF even after controlling for covariates. Semiquantitative is able to detect a greater number of incidences of MVD compared to visual methods alone. Further studies are needed to determine whether treatment of MVD is beneficial in NICM.

Safety and Efficacy of Regadenoson for Pediatric Stress Perfusion Cardiac MRI with Quantification of Myocardial Blood Flow.

Myocardial stress perfusion magnetic resonance imaging is a non-invasive tool to assess for myocardial ischemia and viability. Pediatric myocardial stress perfusion MRI can be challenging due to multiple intravenous lines, sedation, inadequate breath holding, fast heart rates, and complex anatomy. We performed a retrospective analysis in 39 children to evaluate safety and efficacy of regadenoson, a coronary vasodilator administered via a single intravenous line (6–10 mcg/kg), with respiratory motion correction (MOCO) and semi-quantitative blood flow analysis. Stress response data and adverse events were recorded, and image quality compared between native and MOCO reconstructions, assessing for perfusion deficits. Semi-quantitative analysis compared myocardial perfusion reserve index (MPRI) between patients who had a focal perfusion defect, patients who had undergone an orthotopic heart transplant, and non-transplant patients with no focal defects. Stress perfusion was completed in 38/39 patients (median age 15 years with a 41 ± 27% rise in heart rate (p < 0.005). Fifteen out of thirty-eight had transient minor side effects with no major adverse events. MOCO image quality was better than non-MOCO (4.63 vs. 4.01 at rest, p < 0.005: 4.41 vs. 3.84 at stress, p < 0.005). Reversible perfusion defects were seen in 4/38 patients with lower segmental mean MPRI in the area of the perfusion defect, nearing statistical significance when compared to non-transplant patients with no defects (0.78 ± 0.22 vs. 0.99 ± 0.36, p = 0.07). The global MPRI of the 16 patients who had undergone orthotopic heart transplant was significantly lower than the non-transplant patients (0.75 ± 0.22 vs. 0.92 ± 0.23, p = 0.03). Regadenoson is a safe and effective coronary vasodilator for pediatric stress perfusion MRI with MOCO producing better image quality and allowing for semi-quantitative assessment of perfusion deficits that correlate with qualitative assessment.

Relation of Myocardial Perfusion Reserve and Left Ventricular Ejection Fraction in Ischemic and Nonischemic Cardiomyopathy

Quantification of myocardial perfusion reserve (MPR) using vasodilator stress cardiac magnetic resonance is increasingly used to detect coronary artery disease. However, MPR can also be altered because of changes in microvascular function. We aimed to determine whether MPR can distinguish between ischemic cardiomyopathy (IC) secondary to coronary artery disease and non-IC (NIC) with microvascular dysfunction and no underlying epicardial coronary disease. A total of 60 patients (mean age 65 ± 14 years, 30% women), including 31 with IC and 29 with NIC, were identified from a pre-existing vasodilator stress cardiac magnetic resonance registry. Short-axis cine slices were used to measure left ventricular ejection fraction (LVEF) using the Simpson method of disks. MPR index (MPRi) was determined from first-pass myocardial perfusion images during stress and rest using the upslope ratio, normalized for the arterial input and corrected for rate pressure product. Patients in both groups were divided into subgroups of LVEF ≤35% and LVEF >35%. Differences in MPRi between the subgroups were examined. MPRi was moderately correlated with LVEF in patients with NIC (r=0.53, p=0.03), whereas the correlation in patients with IC was lower (r=0.32, p=0.22). Average LVEF in NIC and IC was 34% ± 8% and 35% ± 8%, respectively (p=0.63). MPRi was not significantly different in IC compared with NIC (1.17 [0.88 to 1.61] vs 1.23 [1.07 to 1.66], p=0.41), including the subgroups of LVEF (IC: 1.20 ± 0.56 vs NIC: 1.15 ± 0.24, p=0.75 for LVEF ≤35% and IC: 1.35 ± 0.44 vs NIC: 1.58 ± 0.50, p=0.19 for LVEF >35%). However, MPRi was significantly lower in patients with LVEF ≤35% compared with those with LVEF>35% (1.17 ± 0.40 vs 1.47 ± 0.47, p=0.01). Similar difference between LVEF groups was noted in the patients with NIC (1.15 ± 0.24 vs 1.58 ± 0.50, p=0.006) but not in the patients with IC (1.20 ± 0.56 vs 1.35 ± 0.44, p=0.42). MPRi can be abnormal in the presence of left ventricular dysfunction with nonischemic etiology. This is a potential pitfall to consider when using this approach to detect ischemia because of epicardial coronary disease using myocardial perfusion imaging.

Surveillance of Chronic Graft Failure Utilizing Cardiac Magnetic Resonance Imaging in Pediatric Heart Transplantation

<h3>Purpose</h3> The cause of chronic graft failure (CGF) in heart transplantation (HT) is multifactorial including cardiac allograft vasculopathy (CAV) and rejection. Previous studies have shown that endomyocardial biopsy (EMB) can detect fibrosis and microvessel disease (MVD) in patients with CGF. We sought to evaluate associations between, 1. CAV, 2. Historical moderate to severe (M/S) rejection, and 3. Histopathologic changes of CGF on EMB with cardiac magnetic resonance imaging (CMR) parameters to assess its use as a non-invasive surveillance modality for CGF in pediatric heart transplant patients (PHT). <h3>Methods</h3> Retrospective evaluation of PHT who underwent CMR between 9/2015 and 10/2021 was performed. Those with EMB within 6 months of CMR were included; PHT with M/S rejection on EMB were excluded. CAV was assessed per ISHLT guidelines. Historical M/S rejection, included PHT with a history of ACR >2R or AMR>2. CMR included assessment of cardiac function, myocardial edema (T2 mapping), fibrosis (pre-contrast T1 mapping and extracellular volume fraction), and myocardial perfusion reserve index (MPRi) calculated from stress perfusion imaging. On EMB, fibrosis was qualitatively scored on a scale of 0-5 and MVD was quantified as number of capillaries with stenotic wall thickening per fields of view. Wilcoxon rank sum test or Spearman rank correlation investigated relationships between presence of CAV, historical M/S rejection, EMB and CMR findings. Unadjusted p-values are reported. <h3>Results</h3> Forty-one PHT with median age at CMR of 15.7 years (11.6,19.3) and time from HT of 6.4 years (4.1,11.0) were studied. CAV was present in 9/41(22.0%), although only 2/9 had greater than CAV 1. Historical M/S rejection was present in 14/41 (34.2%). Presence of CAV was associated with lower LVEF (60% vs 56%; p=0.03), higher peak T2 (53 vs 56 ms; p=0.04). Historical M/S rejection was associated with higher global T2 (47 vs 49 ms; p=0.01) and peak T2 (53 vs 57 ms; p=0.02). Higher fibrosis score on EMB was associated with lower MPRi on CMR (rho= -0.35; p=0.04). <h3>Conclusion</h3> Abnormalities in CMR parameters are noted in those with CAV, historical M/S rejection, and greater fibrosis on EMB in a relatively healthy PHT cohort. Longitudinal follow up studies in larger cohorts may aid in further refining the role of CMR in CGF surveillance.

Subclinical hepatic fibrosis is associated with coronary microvascular dysfunction by myocardial perfusion reserve index: a retrospective cohort study.

The heart-liver axis is of growing importance. Previous studies have identified independent association of liver dysfunction and fibrosis with adverse cardiac outcomes, but mechanistic pathways remain uncertain. We sought to understand the relations between the degree of hepatic fibrosis identified by the Fibrosis-4 (Fib-4) risk score and comprehensive cardiac MRI (CMR) measures of subclinical cardiac disease. We conducted a retrospective single-center cohort study of patients between 2011 and 2021. We identified consecutive patients who underwent a comprehensive CMR imaging protocol including contrast enhanced with stress/rest perfusion, and lacked pre-existing cardiovascular disease or perfusion abnormalities on CMR. We examined the association of hepatic fibrosis, using the Fib-4 score, with subclinical cardiac disease on CMR while adjusting for cardiometabolic traits. Given known associations of hepatic disease and coronary microvascular dysfunction, we prioritized analyses with the myocardial perfusion reserve index (MPRI), a marker of coronary microvascular function. Of the 66 patients in our study cohort, 54 were female (81%) and the mean age was 53.7 ± 15.3years. We found that higher Fib-4 was associated with reduction in the MPRI (β [SE] - 1.12 [0.46], P = 0.02), after adjusting for cardiometabolic risk factors. Importantly, Fib-4 was not significantly associated with any other CMR phenotypes including measures of cardiac remodeling, inflammation, fibrosis, or dysfunction. We found evidence that hepatic fibrosis associated with coronary microvascular dysfunction, in the absence of overt associations with any other subclinical cardiac disease measures. These findings highlight a potentially important precursor pathway leading to development of subsequent heart-liver disease.