Global Myocardial Perfusion Reserve Research Articles

Investigating the cardiac manifestations of IgG4-related disease using cardiac magnetic resonance imaging

Abstract Introduction IgG4-related disease (IgG4-RD) is a relapsing-remitting immune-mediated condition that affects multiple organ systems. Case reports of suspected cardiovascular involvement in IgG4-RD have emerged though no study has systematically assessed the cardiovascular phenotype of IgG4-RD using cardiac magnetic resonance (CMR) imaging. Purpose We systematically assessed patients with IgG4-RD using CMR to identify the cardiovascular manifestations, and compared them to controls. Methods We recruited 11 patients with histologically-confirmed IgG4-RD (6 female, 61±11 years, 9 with active disease (8 with pancreatic involvement, 3 parotid, 5 bile ducts, 5 kidneys and 3 cardiovascular)). Patients underwent CMR at 1.5T including cine, myocardial tagging, native T1-mapping, late gadolinium enhancement (LGE), extracellular volume (ECV) and quantitative stress perfusion mapping. Results were compared to 10 healthy controls with no cardiac disease (50% female, 35±8 years). Results are presented as mean ± standard deviation (SD) unless otherwise stated. Results Patients with IgG4-RD had similar cardiac geometry to the reference group (Table 1), with similar biventricular and bi-atrial volumes. However, despite similar biventricular ejection fractions compared to controls (patient LVEF: 55-67%, RVEF: 51-65%), IgG4-RD patients showed significantly reduced global longitudinal strain (GLS) (-16.8 ± 2.3% vs -18.7 ± 1.6%, p=0.045). Furthermore, 64% (7/11) of IgG4-RD patients showed LGE, 6 of whom showed non-ischaemic patterns (Figure 1). Male IgG4-RD patients (n=5) as a group showed a significantly higher average myocardial T1 value relative to the reference group, with 3/5 male patients having an abnormally high myocardial T1 (above the 2SD limit of normal). Female IgG4-RD patients (n=6) had similar and normal myocardial T1 values to the reference group. ECV did not significantly differ between the two groups. IgG4-RD patients showed a significantly reduced global myocardial perfusion reserve (MPR), including two patients with a qualitative inducible perfusion defect. Only 3 out of the 11 IgG4-RD patients had a completely normal CMR. Conclusion Patients with IgG4-RD show frequent cardiac abnormalities as revealed by advanced CMR phenotyping. These include subclinical systolic dysfunction, ischaemic and non-ischaemic myocardial fibrosis, reduced myocardial perfusion reserve, and elevated myocardial T1 times. These abnormalities have been described in inflammatory cardiovascular diseases, supporting a plausible pathophysiological link with IgG4-RD. Future work in larger and multicentre cohorts is warranted, to systematically define the novel cardiovascular phenotype of IgG4-RD.Table 1Figure 1

Associations of cardiovascular and diabetes-related risk factors with myocardial perfusion reserve assessed by 201Tl/99mTc-tetrofosmin single-photon emission computed tomography in patients with diabetes mellitus and stable coronary artery disease.

We aimed to examine the associations of cardiovascular risk factors with myocardial perfusion reserve (MPR) in patients with type 2 diabetes and stable coronary artery disease. The study patients were retrospectively identified from a database of patients with diabetes and stable coronary artery disease at Asan Medical Center (Seoul, Republic of Korea), covering the period from 2017 to 2019. The primary outcome variable was MPR assessed by dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT. Univariable and stepwise multivariable analyses were performed to assess the associations of cardiovascular risk factors with MPR. A total of 276 patients (236 men and 40 women) were included. The median global MPR was 2.4 (interquartile range 1.9-3.0). Seventy-five (27.2%) patients had an MPR < 2.0. Multivariable linear regression showed that smoking (ß = - 0.44, 95% confidence interval - 0.68 to - 0.21, P < 0.001), hypertension (ß = - 0.24, 95% confidence interval - 0.47 to - 0.02, P = 0.033), and summed difference score (ß = - 0.05, 95% confidence interval - 0.07 to - 0.03, P < 0.001) were independently associated with MPR. Abnormal MPR (< 2.0) was associated with a higher incidence of cardiac death or myocardial infarction (P = 0.034). MPR assessed by dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT was impaired in a large cohort of patients with diabetes. After adjusting for risk variables, including standard myocardial perfusion imaging characteristics, smoking, and hypertension were associated with MPR. Our results may aid in identifying patients with impaired MPR and stratifying patients with type 2 diabetes.

Abnormal left ventricular subendocardial perfusion and diastolic function in women with obesity and heart failure and preserved ejection fraction

Purpose– Coronary microvascular dysfunction (CMD) is common in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. Stress cardiovascular magnetic resonance (CMR) has been proposed as a non-invasive tool for detection of CMD. The aim of this study was to determine relationship between CMD and diastolic function in patients with HFpEF using a novel CMR technique.Methods– Patients with obesity and HFpEF without epicardial coronary artery disease (CAD) underwent Doppler echocardiography to measure diastolic function, followed by vasodilator stress CMR, using a single bolus, dual sequence, quantitative myocardial perfusion mapping to measure myocardial blood flow (MBF) at rest and at peak hyperemia. With this, myocardial perfusion reserve (MPR), global stress endocardial-to-epicardial (endo:epi) perfusion ratio, and total ischemic burden (IB, defined as myocardial segments with MBF < 1.94 mL/min/g) were calculated. Results are reported as median and interquartile range.Results– Nineteen subjects were enrolled (100% female, 42% Black). Median age was 64 [56–72] years. Global stress MBF was 2.43 ml/min/g [2.16–2.78] and global myocardial perfusion reserve (MPR) was 2.34 [2.07–2.88]. All had an abnormal subendocardial perfusion with an endo:epi of less than 1 (0.87 [0.81–0.90]). Regional myocardial hypoperfusion was detected in 14 (74%) patients with an IB of 6% [0-34.4]. Endo:epi ratio significantly correlated with IB (R=-0.510, p = 0.026) and measures of diastolic function (R = 0.531, p = 0.019 and R=-0.544, p = 0.014 for e’ and E/e’ respectively).Conclusion– Using a novel quantitative stress CMR myocardial perfusion mapping technique, women with obesity and HFpEF were found to have patterns of abnormal subendocardial perfusion which significantly correlated with measures of diastolic dysfunction.

Abstract 11734: Myocardial Perfusion Reserve Quantified by Stress Cardiovascular Magnetic Resonance Imaging is Reduced in Long COVID Patients Presenting With Chest Pain

Introduction: Chest pain is common in patients with Post-acute Sequelae of SARS-CoV-2 (PASC), also known as long COVID, but the mechanism is unknown. Hypothesis: We hypothesized that PASC patients with chest pain have impaired myocardial perfusion reserve (MPR) measured by stress perfusion cardiovascular magnetic resonance (CMR) imaging. Methods: We retrospectively identified the first 30 consecutive patients who underwent clinically ordered adenosine stress perfusion CMR for chest pain persisting &gt;4 weeks after SARS-CoV-2 infection (PASC). Patients with a history of coronary artery disease (CAD) or left ventricular ejection fraction (LVEF) &lt;50% were excluded. Patients without a history of SARS-CoV-2 infection who had a normal clinically ordered perfusion CMR served as controls. A previously-described automated pixel-wise quantitative perfusion tool was used to calculate stress and rest myocardial blood flow (MBF) in mL/min/g, and MPR as the ratio of stress MBF/rest MBF. The cutoff for reduced MPR was &gt;2 SD below mean MPR for controls. Results: In 30 PASC (67% female, age 43±13) and 13 controls (54% female, age 50±12), with LVEF (61±6% vs 59±8%), native T1 (1001±49 vs 992±57 ms), T2 (49.5±3.7 vs 48.0±3.3 ms), and ECV (24.6±2.9 vs 24.6±2.6%) were similar (p&gt;0.2 for all). Prior pericarditis (n=2) or prior myocarditis (n=3) were infrequent, with no acute disease by CMR. PASC patients had significantly lower global MPR than controls (1.54±0.25 vs. 2.20±0.36, p&lt;0.001), and 16/30 (53%) PASC patients had reduced MPR (&lt;1.49). Clinical ischemia evaluation revealed obstructive CAD in only 2 PASC patients. Conclusions: In PASC patients with chest pain undergoing stress perfusion CMR, global MPR is frequently reduced and is significantly lower than in patients with normal clinical perfusion CMR and no history of SARS-CoV-2 infection. This study raises the possibility that microvascular dysfunction is an important cause of chest pain in patients with long COVID.

A cardiovascular magnetic resonance imaging-based pilot study to assess coronary microvascular disease in COVID-19 patients

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and is primarily characterised by a respiratory disease. However, SARS-CoV-2 can directly infect vascular endothelium and subsequently cause vascular inflammation, atherosclerotic plaque instability and thereby result in both endothelial dysfunction and myocardial inflammation/infarction. Interestingly, up to 50% of patients suffer from persistent exercise dyspnoea and a post-viral fatigue syndrome (PVFS) after having overcome an acute COVID-19 infection. In the present study, we assessed the presence of coronary microvascular disease (CMD) by cardiovascular magnetic resonance (CMR) in post-COVID-19 patients still suffering from exercise dyspnoea and PVFS. N = 22 patients who recently recovered from COVID-19, N = 16 patients with classic hypertrophic cardiomyopathy (HCM) and N = 17 healthy control patients without relevant cardiac disease underwent dedicated vasodilator-stress CMR studies on a 1.5-T MR scanner. The CMR protocol comprised cine and late-gadolinium-enhancement (LGE) imaging as well as velocity-encoded (VENC) phase-contrast imaging of the coronary sinus flow (CSF) at rest and during pharmacological stress (maximal vasodilation induced by 400 µg IV regadenoson). Using CSF measurements at rest and during stress, global myocardial perfusion reserve (MPR) was calculated. There was no difference in left ventricular ejection-fraction (LV-EF) between COVID-19 patients and controls (60% [57–63%] vs. 63% [60–66%], p = NS). There were only N = 4 COVID-19 patients (18%) showing a non-ischemic pattern of LGE. VENC-based flow measurements showed that CSF at rest was higher in COVID-19 patients compared to controls (1.78 ml/min [1.19–2.23 ml/min] vs. 1.14 ml/min [0.91–1.32 ml/min], p = 0.048). In contrast, CSF during stress was lower in COVID-19 patients compared to controls (3.33 ml/min [2.76–4.20 ml/min] vs. 5.32 ml/min [3.66–5.52 ml/min], p = 0.05). A significantly reduced MPR was calculated in COVID-19 patients compared to healthy controls (2.73 [2.10–4.15–11] vs. 4.82 [3.70–6.68], p = 0.005). No significant differences regarding MPR were detected between COVID-19 patients and HCM patients. In post-COVID-19 patients with persistent exertional dyspnoea and PVFS, a significantly reduced MPR suggestive of CMD—similar to HCM patients—was observed in the present study. A reduction in MPR can be caused by preceding SARS-CoV-2-associated direct as well as secondary triggered mechanisms leading to diffuse CMD, and may explain ongoing symptoms of exercise dyspnoea and PVFS in some patients after COVID-19 infection.

Comparison of empagliflozin and sitagliptin therapy on myocardial perfusion reserve in diabetic patients with coronary artery disease.

Sodium-glucose co-transporter 2 inhibitors reduce the risk of cardiovascular events in type 2 diabetic patients with coronary artery disease (CAD); however, the underlying mechanisms remain unclear. We compared the effects of empagliflozin vs. sitagliptin therapy on myocardial perfusion reserve (MPR) using dynamic single-photon emission computed tomography (SPECT) imaging. In total, 100 patients with type 2 diabetes, CAD and an MPR <2.5 were randomized to receive either empagliflozin (10 mg once daily) or sitagliptin (100 mg once daily). Dynamic SPECT examinations were performed at baseline and at 6 months. The primary endpoint was the percent change of global MPR. Evaluable SPECT data were available for 98 patients. Baseline clinical characteristics and SPECT data were well balanced between the two groups. At a 6-month follow-up, the fasting glucose and glycated hemoglobin levels significantly decreased in both groups. Hematocrit and hemoglobin levels significantly increased in the empagliflozin group but not in the sitagliptin group. The global MPR significantly improved after treatment in both groups (34.5 ± 70.6%; P = 0.005 for empagliflozin vs. 22.4 ± 45.7%; P = 0.024 for sitagliptin). However, there was no significant difference in the global MPR between the two groups (P = 0.934). Similar findings were detected with regard to the regional MPR. Among patients with type 2 diabetes and CAD, both empagliflozin and sitagliptin significantly improved the global MPR with no significant difference between the groups.

Cardiac magnetic resonance for asymptomatic patients with type 2 diabetes and cardiovascular high risk (CATCH): a pilot study

BackgroundStress cardiovascular magnetic resonance (CMR) to screen for silent myocardial ischaemia in asymptomatic high risk patients with type 2 diabetes mellitus (DM) has never been performed, and its effectiveness is unknown. Our aim was to determine the feasibility of a screening programme using stress CMR by obtaining preliminary data on the prevalence of silent ischaemia caused by obstructive coronary artery disease (CAD) and quantify myocardial perfusion in asymptomatic high risk patients with type 2 diabetes.MethodsIn this prospective cohort study, we recruited 63 asymptomatic DM patients (mean age 66 years ± 4.4 years; 77.8% male); with Framingham risk score ≥ 20% from 3 sites from June 2017 to August 2018. Normal volunteers were recruited to determine normal global myocardial perfusion reserve index (MPRI). Adenosine stress CMR and global MPRI was performed and measured in all subjects. Positive stress CMR cases were referred for catheter coronary angiography (CCA) with/without fractional flow reserve (FFR) measurements. Positive CCA was defined as an FFR ≤ 0.8 or coronary narrowing ≥ 70%. Patients were followed up for major adverse cardiovascular events. Prevalence is presented as patient numbers and percentage. Mann–Whitney U test was used to compare global MPRI between patients and normal volunteers.Results13 patients had positive stress CMR with positive CCA (20.6% of patient population), while 9 patients with positive stress CMR examinations had a negative CCA. 5 patients (7.9%) had infarcts detected of which 2 patients had no stress perfusion defects. 12 patients had coronary artery stents inserted, whilst 1 patient declined stent placement. DM patients had lower global MPRI than normal volunteers (n = 7) (1.43 ± 0.27 vs 1.83 ± 0.31 respectively; p < 0.01). After a median follow-up of 653 days, there was no death, heart failure, acute coronary syndrome hospitalisation or stroke.Conclusion20.6% of asymptomatic DM patients (with Framingham risk ≥ 20%) had silent obstructive CAD. Furthermore, asymptomatic patients have reduced global MPRI than normal volunteers.Trial Registration: ClinicalTrials.gov Registration Number: NCT03263728 on 28th August 2017; https://clinicaltrials.gov/ct2/show/NCT03263728.

Machine learning in the integration of simple variables for identifying patients with myocardial ischemia

BackgroundA significant number of variables are obtained when characterizing patients suspected with myocardial ischemia or at risk of MACE. Guidelines typically use a handful of them to support further workup or therapeutic decisions. However, it is likely that the numerous available predictors maintain intrinsic complex interrelations. Machine learning (ML) offers the possibility to elucidate complex patterns within data to optimize individual patient classification. We evaluated the feasibility and performance of ML in utilizing simple accessible clinical and functional variables for the identification of patients with ischemia or an elevated risk of MACE as determined through quantitative PET myocardial perfusion reserve (MPR). Methods1,234 patients referred to Nitrogen-13 ammonia PET were analyzed. Demographic (4), clinical (8), and functional variables (9) were retrieved and input into a cross-validated ML workflow consisting of feature selection and modeling. Two PET-defined outcome variables were operationalized: (1) any myocardial ischemia (regional MPR < 2.0) and (2) an elevated risk of MACE (global MPR < 2.0). ROC curves were used to evaluate ML performance. Results16 features were included for boosted ensemble ML. ML achieved an AUC of 0.72 and 0.71 in identifying patients with myocardial ischemia and with an elevated risk of MACE, respectively. ML performance was superior to logistic regression when the latter used the ESC guidelines risk models variables for both PET-defined labels (P < .001 and P = .01, respectively). ConclusionsML is feasible and applicable in the evaluation and utilization of simple and accessible predictors for the identification of patients who will present myocardial ischemia and an elevated risk of MACE in quantitative PET imaging.

Low-dose dynamic myocardial perfusion imaging by CZT-SPECT in the identification of obstructive coronary artery disease.

We measured myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) by a dynamic low-dose CZT-SPECT protocol in patients with suspected or known coronary artery disease (CAD) and investigated the capability of dynamic data in predicting obstructive CAD. A total of 173 patients with suspected or known CAD underwent dynamic CZT-SPECT after the injection of 155MBq and 370MBq of 99mTc-sestamibi for rest and stress imaging, respectively. Standard rest and stress imaging were performed at the end of each dynamic scan. A total perfusion defect (TPD) < 5% were considered normal. Obstructive CAD was defined as ≥ 70% stenosis at coronary angiography. Global MPR was lower (p < 0.05) in patients with abnormal compared with those with normal MPI (2.40 ± 0.7 vs. 2.70 ± 0.8). A weak, albeit significant correlation between TPD and MPR (r = - 0.179, p < 0.05) was found. In 91 patients with available angiographic data, hyperemic MBF (2.59 ± 1.2 vs. 3.24 ± 1.1ml/min/g) and MPR (1.96 ± 0.7 vs. 2.74 ± 0.9) were lower (both p < 0.05) in patients with obstructive CAD (n = 21) compared with those without (n = 70). At univariable analysis, TPD, hyperemic MBF, and MPR were significant predictors of obstructive CAD, whereas only MPR was independent predictor at multivariable analysis (p < 0.05). At per vessels analysis, regional hyperemic MBF (2.59 ± 1.2 vs. 3.24 ± 1.1ml/min/g) and regional MPR (1.96 ± 0.7 vs. 2.74 ± 0.9) were lower in the 31 vessels with obstructive CAD compared with 242 vessels without (both p < 0.05). In patients with suspected or known CAD, MPR assessed by low-dose dynamic CZT-SPECT showed a good correlation with myocardial perfusion imaging findings and it could be useful to predict obstructive CAD.

Quantitative 3D myocardial perfusion with an efficient arterial input function.

The purpose of this study was to further develop and combine several innovative sequence designs to achieve quantitative 3D myocardial perfusion. These developments include an optimized 3D stack-of-stars readout (150 ms per beat), efficient acquisition of a 2D arterial input function, tailored saturation pulse design, and potential whole heart coverage during quantitative stress perfusion. All studies were performed free-breathing on a Prisma 3T MRI scanner. Phantom validation was used to verify sequence accuracy. A total of 21 subjects (3 patients with known disease) were scanned, 12 with a rest only protocol and 9 with both stress (regadenoson) and rest protocols. First pass quantitative perfusion was performed with gadoteridol (0.075 mmol/kg). Implementation and quantitative perfusion results are shown for healthy subjects and subjects with known coronary disease. Average rest perfusion for the 15 included healthy subjects was 0.79 ± 0.19 mL/g/min, the average stress perfusion for 6 healthy subject studies was 2.44 ± 0.61 mL/g/min, and the average globalmyocardial perfusion reserve ratio for 6 healthy subjects was 3.10 ± 0.24. Perfusion deficits for 3 patients with ischemia are shown. Average resting heart rate was 59 ± 7 bpm and the average stress heart rate was 81 ± 10 bpm. This work demonstrates that a quantitative 3D myocardial perfusion sequence with the acquisition of a 2D arterial input function is feasible at high stress heart rates such as during stress. T1 values and gadolinium concentrations of the sequence match the reference standard well in a phantom, and myocardial rest and stress perfusion and myocardial perfusion reserve values are consistent with those published in literature.

P6484Invasive and non-invasive characterisation of low gradient aortic stenosis

Abstract Background Low gradient severe aortic stenosis (LGAS) is associated with unfavourable outcomes when compared to high gradient aortic stenosis (HGAS), yet the contributing pathophysiology is poorly understood. Methods Symptomatic LGAS and HGAS patients undergoing trans-catheter aortic valve implantation (TAVI) underwent 3T stress perfusion cardiac magnetic resonance imaging (CMR) pre-(within 24 hours) and post-(4–6 months) TAVI. Left ventricular (LV) contractility and coronary flow/pressure were measured during hyperaemia and rapid pacing, immediately before and after TAVI, using a conductance LV catheter and dual-pressure and Doppler sensor–tipped guidewire in the mid-left anterior descending coronary artery. Results 24 patients were recruited resulting in 19 suitable datasets (LGAS N=9, HGAS N=10, equally matched for comorbidities and B-natriuretic peptide level). LGAS patients had a smaller LV end diastolic volume index (p=0.035) and lower LV mass index (LVMI) (p=0.037). Pre-TAVI stress global endocardium-epicardium gradient was 0.88±0.09 and global myocardial perfusion reserve (MPR) 2.0±0.48 in 14 patients (6 LGAS and 8 HGAS patients, no difference between groups). Pre-TAVI, baseline coronary data demonstrated lower augmentation pressure (AP, p=0.035) and augmentation index (AIx, p=0.02) in the LGAS group. LGAS patients also exhibited a shorter ejection time (p=0.015), larger forward compression waves during rest, hyperaemia and rapid pacing, and smaller backward expansion waves (BEW) (p=0.001). Lower baseline end systolic pressure (p=0.004), inotropy (dP/dt+, p=0.045), lusitropy (dP/dt-, p=0.069), and stroke work (p=0.019) were observed in the LGAS group. Whilst LV size was smaller the LGAS group, rapid pacing induced a more significant drop in end systolic volume (p=0.045) and ejection fraction (p=0.015) in patients with HGAS. Post-TAVI, the hyperaemic BEW fell sharply (p&lt;0.001), along with coronary VTI (p=0.02), and average pulse velocity (p=0.028), and AP and AIx remained lower (p=0.034 and p=0.031, respectively). The forward expansion wave was reduced in LGAS during rapid pacing. The HGAS group displayed a more profound drop in dP/dt+ (p=0.011) and dP/dt- p=0.014) at rest following intervention. Repeat CMR demonstrated statistically significant reduction in LV size and LVMI (p=0.012 and p&lt;0.001, respectively) with significant increase in 3D global peak radial, circumferential and longitudinal strain (p=0.004, p=0.001 and p=0.018, respectively). Post-TAVI stress global endocardium-epicardium gradient was 0.88±0.13 and MPR 2.46±0.59 (improved from pre-TAVI, p=0.05). There was no difference in remodelling patterns or perfusion between the two groups. Conclusion This is the first study detailing the combined invasive and CMR pathophysiological changes in LGAS. Despite invasive parameters indicating a disease of less severe AS, the level of perfusion abnormality is disproportionate which may in part, relate to their adverse prognosis. Acknowledgement/Funding This research is funded by a Clinical Research Training Fellowship grant from the British Heart Foundation (FS/16/51/32365).

Frequency of Coronary Microvascular Dysfunction and Diffuse Myocardial Fibrosis (Measured by Cardiovascular Magnetic Resonance) in Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is frequently accompanied by co-morbidities and a systemic proinflammatory state, resulting in coronary microvascular dysfunction (CMD), as well as myocardial fibrosis. The purpose of this study is to examine the relation between myocardial perfusion reserve (MPR) and diffuse myocardial fibrosis in patients with HFpEF using cardiovascular magnetic resonance. A single center study was performed in 19 patients with clinical HFpEF and 15 healthy control subjects who underwent quantitative first-pass perfusion imaging to calculate global MPR. T1 mapping was used to assess fibrosis and to calculate extracellular volume. Spiral cine displacement encoded stimulated echo was used to calculate myocardial strain. Comprehensive 2D echocardiograms with speckle tracking, cardiopulmonary exercise testing, and brain natriuretic peptide levels were also obtained. In patients with HFpEF, mean left ventricular EF was 61% ± 9% and left ventricular mass index 45 ± 12 g/m2. Compared with controls, HFpEF patients had reduced global MPR (2.29 ± 0.64 vs 3.38 ± 0.76, p = 0.002) and VO2 max (16.5 ± 6.8 vs 30.9 ± 7.7 ml/kg min, p <0.001) whereas extracellular volume (0.29 ± 0.04 vs 0.25 ± 0.04, p = 0.02), pulmonary artery systolic pressure (35.4 ± 13.7 vs 22.3 ± 5.4 mm Hg, p = 0.004), and average E/e' (15.0 ± 7.6 vs 8.6 ± 2.0, p = 0.005) were increased. Displacement encoded stimulated echo peak systolic circumferential strain (p = 0.60) as well as echocardiographic derived global longitudinal strain (p = 0.07) were similar between both groups. The prevalence of CMD, defined as global MPR <2.5, in the HFpEF group was 69%. In conclusion, HFpEF patients have a high prevalence of CMD and diffuse fibrosis. These parameters may be useful clinical end points for future therapeutic trials.

Microvascular Dysfunction in Dilated Cardiomyopathy: A Quantitative Stress Perfusion Cardiovascular Magnetic Resonance Study

ObjectivesThis study sought to quantify myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) in dilated cardiomyopathy (DCM) and examine the relationship between myocardial perfusion and adverse left ventricular (LV) remodeling. BackgroundAlthough regarded as a nonischemic condition, DCM has been associated with microvascular dysfunction, which is postulated to play a role in its pathogenesis. However, the relationship of the resulting perfusion abnormalities to myocardial fibrosis and the degree of LV remodeling is unclear. MethodsA total of 65 patients and 35 healthy control subjects underwent adenosine (140 μg/kg/min) stress perfusion cardiovascular magnetic resonance with late gadolinium enhancement imaging. Stress and rest MBF and MPR were derived using a modified Fermi-constrained deconvolution algorithm. ResultsPatients had significantly higher global rest MBF compared with control subjects (1.73 ± 0.42 ml/g/min vs. 1.14 ± 0.42 ml/g/min; p < 0.001). In contrast, global stress MBF was significantly lower versus control subjects (3.07 ± 1.02 ml/g/min vs. 3.53 ± 0.79 ml/g/min; p = 0.02), resulting in impaired MPR in the DCM group (1.83 ± 0.58 vs. 3.50 ± 1.45; p < 0.001). Global stress MBF (2.70 ± 0.89 ml/g/min vs. 3.44 ± 1.03 ml/g/min; p = 0.017) and global MPR (1.67 ± 0.61 vs. 1.99 ± 0.50; p = 0.047) were significantly reduced in patients with DCM with LV ejection fraction ≤35% compared with those with LV ejection fraction >35%. Segments with fibrosis had lower rest MBF (mean difference: −0.12 ml/g/min; 95% confidence interval: −0.23 to −0.01 ml/g/min; p = 0.035) and lower stress MBF (mean difference: −0.15 ml/g/min; 95% confidence interval: −0.28 to −0.03 ml/g/min; p = 0.013). ConclusionsPatients with DCM exhibit microvascular dysfunction, the severity of which is associated with the degree of LV impairment. However, rest MBF is elevated rather than reduced in DCM. If microvascular dysfunction contributes to the pathogenesis of DCM, then the underlying mechanism is more likely to involve stress-induced repetitive stunning rather than chronic myocardial hypoperfusion.

Myocardial perfusion assessed with cardiac computed tomography in women without coronary heart disease

Combined coronary CT angiography and CT perfusion (CTP) is a novel, non-invasive, 'one-stop' diagnostic tool to rule out ischaemia in patients suspected for coronary artery disease (CAD). However, the normal myocardial perfusion pattern by static CTP in humans is poorly described. We aimed to investigate global and regional myocardial perfusion during rest and adenosine-induced hyperaemia in asymptomatic women without history of coronary heart disease (CHD). Using a 320-row CT scanner with a static protocol, semi-quantitative assessment of rest and stress CTP was performed in 34 asymptomatic middle-aged women without obstructive CAD (<50% stenosis) or history of CHD, and with normal exercise stress test and left ventricular (LV) function. Using a 16-segment model, we assessed global and regional values of LV myocardial perfusion reserve (MPR) and transmural perfusion ratio (TPR). Mean±SD age was 56±13years. Resting and hyperaemic myocardial perfusion was heterogeneously distributed throughout the LV myocardium. During hyperaemia, global MPR increased by median (IQR) 158% (144-176) with the highest increase in the right coronary artery territory (171%; P<0.02). Rest and stress segmental TPR values ranged between 0.93-1.26 and 0.99-1.13, respectively, with the lowest values detected in the inferoseptal segments. No differences in perfusion parameters were found between participants with normal epicardial arteries and participants with non-significant epicardial atheromatosis (all P>0.05). Global perfusion parameters were not associated with age or menopausal status (all P>0.05). This descriptive study presents data on global and regional myocardial perfusion in a cohort of healthy middle-aged women.

Myocardial bridging of the left anterior descending coronary artery is associated with reduced myocardial perfusion reserve: a 13N-ammonia PET study

Myocardial Bridging (MB) refers to the band of myocardium that abnormally overlies a segment of a coronary artery. This paper quantitatively evaluates the influence of MB of the left anterior descending artery (LAD) on myocardial perfusion of the entire left ventricle. We studied 131 consecutive patients who underwent hybrid rest/stress 13N-ammonia positron emission tomography (PET) and coronary computed tomography angiography (CCTA) due to suspected myocardial ischemia. Patients with previous myocardial infarction and/or significant coronary artery disease (≥ 50% stenosis) were excluded. Myocardial perfusion measurements were compared between patients with and without LAD-MB. Additionally, we evaluated the relationship between anatomical characteristics (length and depth) of LAD-MB and myocardial perfusion measurements. 17 (13%) patients presented a single LAD-MB. Global myocardial perfusion reserve (MPR) was lower in patients with LAD-MB than in patients without LAD-MB (1.9 ± 0.5 vs. 2.3 ± 0.6, p < 0.01). Global stress myocardial blood flow (MBF) was similar in patients with and without LAD-MB (2.2 ± 0.4 vs. 2.3 ± 0.7 ml/g/min, p = 0.40). Global rest MBF was higher in patients with LAD-MB than in patients without LAD-MB (1.2 ± 0.3 vs. 1.0 ± 0.2 ml/g/min, p < 0.01). Global rest MBF, stress MBF, and MPR quantifications were similar in patients with superficial and deep LAD-MB (all p = NS). We did not find any correlation between length and global rest MBF, stress MBF nor MPR (r = − 0.14, p = 0.59; r = 0.44, p = 0.07; and r = 0.45, p = 0.07 respectively). Quantitative myocardial perfusion suggests that LAD-MB may be related to impaired perfusion reserve, an indicator of microvascular dysfunction. Anatomical characteristics of LAD-MB were not related to changes in myocardial perfusion.

3008Reduced global myocardial perfusion reserve in DCM and HCM patients assessed by CMR-based velocity-encoded coronary sinus flow measurements and first-pass perfusion imaging

3008Reduced global myocardial perfusion reserve in DCM and HCM patients assessed by CMR-based velocity-encoded coronary sinus flow measurements and first-pass perfusion imaging

Reduced global myocardial perfusion reserve in DCM and HCM patients assessed by CMR-based velocity-encoded coronary sinus flow measurements and first-pass perfusion imaging.

Coronary microvascular dysfunction (CMD) is an independent predictor of poor prognosis in patients suffering from dilative or hypertrophic cardiomyopathy (DCM/HCM). To assess CMD, quantitative myocardial first-pass perfusion (1P) cardiovascular magnetic resonance (CMR) can be performed. Coronary sinus flow (CSF) measurements at rest and during maximal vasodilatation are an alternative and well-validated approach for the quantification of global myocardial blood flow (MBF) in CMR. Global myocardial perfusion reserve (MPR) was used to compare both methods, 1P and CSF. This measure reflects the ratio of myocardial blood flow during maximal coronary vasodilatation over rest. 1P-MPR and CSF-MPR were calculated in 17 HCM patients, 14 DCM patients and 16 controls, who underwent a stress CMR study to rule out obstructive coronary artery disease. All patients were examined on a 1.5-T system and the study protocol comprised both, first-pass myocardial perfusion imaging (MPI) and velocity-encoded (VENC) phase-contrast imaging of CSF during rest and adenosine stress. 1P-MPR was significantly decreased only in HCM patients compared to controls (1.14 vs. 1.43, p = 0.045) whereas CSF-MPR was significantly reduced in both patient groups, HCM and DCM, compared to controls (2.38 and 2.07 vs. 3.18, p = 0.041 and p = 0.032). CSF-MBF at maximal stress was significantly lower in HCM and DCM patients compared to the control group (0.11 and 1.23 vs. 1.58ml/min/g, p = 0.008 and p = 0.040). A moderate but significant correlation between CSF-MPR and 1P-MPR was observed (r = 0.39, p = 0.011). A negative correlation between LV wall thickness and CSF-MBF at rest and stress was found in the DCM group using VENC-based CSF measurements (r=- 0.64, p = 0.013 and r=- 0.69, p = 0.006)-but not using 1P-MPI. Post-proceeding analysis regarding 1P-MPR and CSF-MPR measurements required 20.1 and 6.5min, respectively (p < 0.001). The presence of microvascular disease can be non-invasively and quickly detected by VENC-based CSF-MPR measurements during routine stress perfusion CMR in both HCM and DCM patients. Compared to conventional 1P-MPI, VENC-based CSF-MPR is particularly useful in DCM patients with thinned ventricular walls.

5798Diagnostic value of global myocardial perfusion reserve assessment based on two different non-invasive CMR techniques: coronary sinus flow measurements vs. first-pass myocardial perfusion imaging

5798Diagnostic value of global myocardial perfusion reserve assessment based on two different non-invasive CMR techniques: coronary sinus flow measurements vs. first-pass myocardial perfusion imaging

Diagnostic value of global myocardial perfusion reserve assessment based on coronary sinus flow measurements using cardiovascular magnetic resonance in addition to myocardial stress perfusion imaging.

Myocardial perfusion reserve (MPR) is defined as the maximal possible increase in myocardial blood flow (MBF) above baseline conditions. Global MBF can be measured non-invasively by means of coronary sinus flow velocity encoded cine (VENC) cardiovascular magnetic resonance (CMR). We aimed to explore the relationship between global MBF/MPR and the extent and severity of coronary artery disease (CAD) in patients referred for CAD work-up by adenosine-stress CMR. Fifty-eight patients with suspected obstructive CAD underwent both adenosine-stress CMR and invasive coronary angiography. In addition to standard cine- and late gadolinium enhancement (LGE)-imaging, first-pass myocardial perfusion imaging (MPI) and coronary sinus flow measurements (VENC) were performed at rest and during peak stress (after 140 µg/kg/min adenosine), respectively. Nineteen young patients with a very low CAD pre-test probability and normal adenosine-stress CMR formed the control group. Fifty-nine percent (n = 34) of the study group showed segmental, adenosine-induced myocardial perfusion defects compared to none of the control group (P < 0.001). Global MPR was lower in the study group compared to the control group: 2.3 (1.5-3.1) vs. 3.1 (2.0-4.3), P = 0.016. The SYNTAX score was higher in the study group patients with an impaired MPR (<2) compared to those with a preserved MPR (3.0 vs. 16.0, P = 0.01)-mainly due to higher prevalence of proximal epicardial stenoses (60% vs. 27%, P = 0.02) and multi-vessel disease (56% vs. 24%, P = 0.017). The diagnostic yield of stress CMR for the diagnosis of CAD (>50% stenosis) increased from 65to 88% when global MPR assessment was considered in addition to MPI (P = 0.025). Global MBF and MPR values correlate with the anatomical extent and complexity of CAD and increase the diagnostic yield of non-invasive stress CMR in the work-up of CAD. CMR-based MBF and MPR measurements may play a future role in the evaluation of the total ischaemic burden-particularly in patients with multi-vessel disease.

SPECT Myocardial Perfusion Reserve in Patients with Multivessel Coronary Disease: Correlation with Angiographic Findings and Invasive Fractional Flow Reserve Measurements.

Quantification of myocardial perfusion reserve (MPR) is an emerging topic in nuclear cardiology with an expected diagnostic and prognostic incremental value, especially for patients with severe coronary artery disease. The advent of new dedicated solid-state cameras has opened new perspectives for perfusion quantitation in SPECT. We appraised the feasibility of perfusion reserve estimation using a cadmium zinc telluride camera in a cohort of multivessel patients and its pertinence with respect to angiographic data. Twenty-three patients with known multivessel coronary artery disease were prospectively enrolled. Dynamic SPECT acquisitions using (99m)Tc-tetrofosmin at rest and after vasodilator stress were performed using a dedicated cadmium zinc telluride camera. Reconstructed frames were automatically segmented to extract the vascular input function and the myocardial uptake curve. One-compartment kinetic modeling was used to estimate global and regional uptake values, and then myocardial blood flow was derived using the Renkin-Crone equation. Global and regional MPR was assessed using flow difference (stress - rest) and flow ratio (stress/rest). All patients underwent control coronary angiography within 4 wk, which served as the reference for MPR index assessment. Relevant angiographic findings included maximal stenosis and (for a subgroup of 26 vessels) invasive measurement of fractional flow reserve (FFR). A stenosis was considered obstructive if greater than 50% and an FFR abnormal if lower than 0.8. Global MPR correlated well with number of obstructed vessels (P < 0.001). After multivariate analysis, both regional flow ratio and flow difference were significantly associated with maximal stenosis (P < 0.001) and FFR (P < 0.001). Regional MPR indices were significantly different in obstructed and nonobstructed vessels (P < 0.001) and in vessels with normal and abnormal FFR (P < 0.001). With a cutoff of 2, the sensitivity, specificity, and accuracy of regional flow ratio were, respectively, 80%, 85%, and 81% for the detection of obstructed vessels and 89%, 82%, and 85% for the detection of abnormal FFR. Scintigraphic estimations of global and regional MPR in multivessel patients using a cadmium zinc telluride camera appear to correlate well with invasive angiographic findings, including maximal stenosis and FFR measurements.