Left ventricular subclinical myocardial dysfunction in uncomplicated type 2 diabetes mellitus is associated with impaired myocardial perfusion: a contrast-enhanced cardiovascular magnetic resonance study.
ABSTRACT: BACKGROUND:Early detection of subclinical myocardial dysfunction in patients with diabetes mellitus (DM) is essential for recommending therapeutic interventions that can prevent or reverse heart failure, thereby improving the prognosis in such patients. This study aims to quantitatively evaluate left ventricular (LV) myocardial deformation and perfusion using cardiovascular magnetic resonance (CMR) imaging in patients with type 2 diabetes mellitus (T2DM), and to investigate the association between LV subclinical myocardial dysfunction and coronary microvascular perfusion. METHODS:We recruited 71 T2DM patients and 30 healthy individuals as controls who underwent CMR examination. The T2DM patients were subdivided into two groups, namely the newly diagnosed DM group (n?=?31, patients with diabetes for???5 years) and longer-term DM group (n?=?40, patients with diabetes?>?5 years). LV deformation parameters, including global peak strain (PS), peak systolic strain rate, and peak diastolic strain rate (PSDR), and myocardial perfusion parameters such as upslope, time to maximum signal intensity (TTM), and max signal intensity (Max SI, were measured and compared among the three groups. Pearson's correlation was used to evaluate the correlation between LV deformation and perfusion parameters. RESULTS:Pooled data from T2DM patients showed a decrease in global longitudinal, circumferential, and radial PDSR compared to healthy individuals, apart from lower upslope. In addition, increased TTM and reduced Max SI were found in the longer-term diabetics compared to the normal subjects (p?
Project description:BACKGROUND:The microvascular effects of obesity should be considered in diabetic individuals for elucidating underlying mechanisms and developing targeted therapies. This study aims to determine the effect of obesity on myocardial microvascular function in type 2 diabetes mellitus (T2DM) patients using cardiac magnetic resonance (CMR) first-pass perfusion imaging and assessed significant risk factors for microvascular dysfunction. MATERIALS AND METHODS:Between September 2016 and May 2018, 120 patients with T2DM (45.8% women [55 of 120]; mean age, 56.45?±?11.97 years) and 79 controls (44.3% women [35 of 79]; mean age, 54.50?±?7.79 years) with different body mass index (BMI) scales were prospectively enrolled and underwent CMR examination. CMR-derived perfusion parameters, including upslope, time to maximum signal intensity (TTM), maximum signal intensity (MaxSI), MaxSI (-baseline), and SI (baseline), and T2DM related risk factors were analyzed among groups/subgroups both in T2DM patients and controls. Univariable and multivariable linear and logistic regression analyses were performed to assess the potential additive effect of obesity on microvascular dysfunction in diabetic individuals. RESULTS:Compared with controls with comparable BMIs, patients with T2DM showed reduced upslope and MaxSI and increased TTM. For both T2DM and control subgroups, perfusion function gradually declined with increasing BMI, which was confirmed by all perfusion parameters, except for TTM (all P?<?0.01). In multivariable linear regression analysis, BMI (??=?-?0.516; 95% confidence interval [CI], -?0.632 to -?0.357; P?<?0.001), female sex (??=?0.372; 95% CI, 0.215 to 0.475; P?<?0.001), diabetes duration (??=?-?0.169; 95% CI, -?0.319 to -?0.025; P?=?0.022) and glycated haemoglobin (??=?-?0.184; 95% CI, -?0.281 to -?0.039; P?=?0.010) were significantly associated with global upslope in the T2DM group. Multivariable logistic regression analysis indicated that T2DM was an independent predictor of microvascular dysfunction in normal-weight (odds ratio[OR], 6.46; 95% CI, 2.08 to 20.10; P?=?0.001), overweight (OR, 7.19; 95% CI, 1.67 to 31.07; P?=?0.008) and obese participants (OR, 11.21; 95% CI, 2.38 to 52.75; P?=?0.002). CONCLUSIONS:Myocardial microvascular function gradually declined with increasing BMI in both diabetes and non-diabetes status. T2DM was associated with an increased risk of microvascular dysfunction, and obesity exacerbated the adverse effect of T2DM.
Project description:Multiple bloodglucose-lowering agents have been linked to cardiovascular events. Preliminary studies showed improvement in left ventricular (LV) function during glucagon-like peptide-1 receptor agonist administration. Underlying mechanisms, however, are unclear. The purpose of this study was to investigate myocardial perfusion and oxidative metabolism in type 2 diabetic (T2DM) patients with LV systolic dysfunction as compared to healthy controls. Furthermore, effects of 26-weeks of exenatide versus insulin glargine administration on cardiac function, perfusion and oxidative metabolism in T2DM patients with LV dysfunction were explored.Twenty-six T2DM patients with LV systolic dysfunction (cardiac magnetic resonance (CMR) derived LV ejection fraction (LVEF) of 47 ± 13%) and 10 controls (LVEF of 59 ± 4%, P < 0.01 as compared to patients) were analyzed. Both myocardial perfusion during adenosine-induced hyperemia (P < 0.01), and coronary flow reserve (P < 0.01), measured by [15O]H2O positron emission tomography (PET), were impaired in T2DM patients as compared to healthy controls. Myocardial oxygen consumption and myocardial efficiency, measured using [11C]acetate PET and CMR derived stroke volume, were not different between the groups. Eleven patients in the exenatide group and 12 patients in the insulin glargine group completed the trial. Systemic metabolic control was improved after both treatments, although, no changes in cardiac function, perfusion and metabolism were seen after exenatide or insulin glargine.T2DM patients with LV systolic dysfunction did not have altered myocardial efficiency as compared to healthy controls. Exenatide or insulin glargine had no effects on cardiac function, perfusion or oxidative metabolism. Trial registration NCT00766857.
Project description:BACKGROUND:Diabetes mellitus (DM) causes macro- and microvasculopathy, but data on cardiac microvascular changes in large animals are scarce. We sought to determine the effect of DM on macro- and microvascular changes in diabetic pigs and humans. METHODS:Eight domestic pigs (4 with type I diabetes and 4 controls) underwent coronary angiography with optical coherence tomography (OCT; at baseline and 1 and 2 months), coronary computed tomography angiography, cardiac magnet resonance (CMR) imaging, and histologic examination. RESULTS:The diabetic pigs had more irregular capillaries with acellular capillaries and a smaller capillary diameter (11.7 ± 0.33 μm vs. 13.5 ± 0.53 μm; P < 0.001) than those of the control pigs. The OCT showed no significant epicardial stenosis in either group; however diabetic pigs had a greater intima-media thickness. CMR results showed that diabetic pigs had a lower relative upslope at rest (31.3 ± 5.9 vs. 37.9 ± 8.1; P = 0.011) and during stress (18.0 ± 3.0 vs. 21.6 ± 2.8; P = 0.007) than the control pigs, implying decreased myocardial perfusion. Among the 79 patients with ST elevation myocardial infarction, 25 had diabetes and they had lower myocardial perfusion on CMR as well. CONCLUSION:DM causes microvascular remodeling and a decrease in myocardial perfusion in large animals at a very early stage of the disease course. Early and effective interventions are necessary to interrupt the progression of vascular complications in diabetic patients.
Project description:OBJECTIVE:To evaluate the reproducibility of first-pass contrast-enhanced cardiac MR (CMR) myocardial perfusion imaging in patients with non-ischaemic dilated cardiomyopathy (NIDCM). DESIGN:Prospective observational study. SETTING:Single centre, tertiary care hospital. PARTICIPANTS:6 outpatient participants with NIDCM. OUTCOME:Reproducibility of semiquantitative myocardial perfusion analysis by CMR. METHOD:6 patients with NIDCM were studied twice using first-pass of contrast transit through the left ventricular (LV) myocardium with a saturation-recovery gradient echo sequence at rest and during adenosine-induced hyperaemia. The anterior wall was divided into endocardial (Endo) and epicardial (Epi) segments. The Myocardial Perfusion Index (MPI) was calculated as the myocardial signal augmentation rate normalised to the LV cavity rate. The Myocardial Perfusion Reserve Index (MPRI) was calculated as hyperaemic/resting MPI. RESULTS:Between study 1 and 2, median MPI was similar for resting Endo (0.076 vs 0.077), hyperaemic Endo (0.143 vs 0.143), resting Epi (0.073 vs 0.074), and hyperaemic Epi (0.135 vs 0.134). Median MPRI was similar for Endo (1.84 vs 1.87) and Epi (1.90 vs 2.00). Combining Endo and Epi MPI (N=12), there was excellent agreement between Study 1 and 2 for resting MPI (r=0.998, intraclass correlation coefficient (ICC) 0.998, coefficients of variation (CoV) 1.4%), hyperaemic MPI (r=0.979, ICC 0.963, CoV 3.3%) and MPRI (r=0.989, ICC 0.94, CoV 3.8%). CONCLUSIONS:Resting and hyperaemic myocardial perfusion using a normalised upslope analysis during adenosine CMR is a highly reproducible technique in patients with NIDCM. TRIAL REGISTRATION NUMBER:Clinical Trials.Gov ID NCT00574119.
Project description:BACKGROUND:Although diabetes mellitus (DM) and insulin resistance associate with adverse cardiac events, the associations of left ventricular (LV) remodeling and function with compromised glucose metabolism have not been fully evaluated in a general population. We used cardiovascular magnetic resonance (CMR) to evaluate how CMR indices are associated with DM or insulin resistance among participants before developing cardiac events. METHODS:We studied 1476 participants who were free of clinical cardiovascular disease and who underwent tagged CMR in the Multi-Ethnic Study of Atherosclerosis (MESA). LV shape and longitudinal myocardial shortening and torsion were assessed by CMR. A higher sphericity index represents a more spherical LV shape. Multivariable linear regression was used to evaluate the associations of DM or homeostasis model assessment-estimated insulin resistance (HOMA-IR) with CMR indices. RESULTS:In multiple linear regression, longitudinal shortening was lower in impaired fasting glucose than normal fasting glucose (NFG) (0.36% lower vs. NFG, p?<?0.05); torsion was greater in treated DM (0.24 °/cm greater vs. NFG, p?<?0.05) after full adjustments. Among participants without DM, greater log-HOMA-IR was correlated with greater LV mass (3.92 g/index, p?<?0.05) and LV mass-to-volume ratio (0.05 /index, p?<?0.01), and lower sphericity index (-?1.26/index, p?<?0.01). Greater log-HOMA IR was associated with lower longitudinal shortening (-?0.26%/index, p?<?0.05) and circumferential shortening (-?0.30%/index, p?<?0.05). Torsion was positively correlated with log-HOMA-IR until 1.5 of log-HOMA-IR (0.16 °/cm/index, p?=?0.030).), and tended to fall once above 1.5 of log-HOMA-IR (-?0.50 °/cm/index, p?=?0.203). The sphericity index was associated negatively with LV mass-to-volume ratio (-?0.02/%, p?<?0.001) and torsion (-?0.03°/cm/%, p?<?0.001). CONCLUSIONS:Glucose metabolism disorders are associated with LV concentric remodeling, less spherical shape, and reduced systolic myocardial shortening in the general population. Although torsion is higher in participants who are treated for DM and impaired insulin resistance, myocardial shortening was progressively decreased with higher HOMA-IR and torsion was increased only with less severe insulin resistance. CLINICAL TRIAL REGISTRATION:Multi-Ethnic Study of Atherosclerosis (MESA): A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org/ . Study Start Date: January 1999 ( NCT00005487 ).
Project description:<h4>Background</h4>In patients with ischemic heart disease, accurate assessment of the extent of myocardial perfusion deficit may be important in predicting prognosis of clinical cardiac outcomes. The aim of this study was to compare the ability of three dimensional (3D) and of two dimensional (2D) multi-slice myocardial perfusion imaging (MPI) using cardiovascular magnetic resonance (CMR) in determining the size of defects, and to demonstrate the feasibility of 3D MPI in healthy volunteers at 3 Tesla.<h4>Methods</h4>A heart phantom was used to compare the accuracy of 3D and 2D multi-slice MPI in estimating the volume fraction of seven rubber insets which simulated transmural myocardial perfusion defects. Three sets of cross-sectional planes were acquired for 2D multi-slice imaging, where each set was shifted along the partition encoding direction by +/- 10 mm. 3D first-pass contrast-enhanced (0.1 mmol/kg Gd-DTPA) MPI was performed in three volunteers with sensitivity encoding for six-fold acceleration. The upslope of the myocardial time-intensity-curve and peak SNR/CNR values were calculated.<h4>Results</h4>Mean/standard deviation of errors in estimating the volume fraction across the seven defects were -0.44/1.49%, 2.23/2.97%, and 2.59/3.18% in 3D, 2D 4-slice, and 2D 3-slice imaging, respectively. 3D MPI performed in healthy volunteers produced excellent quality images with whole left ventricular (LV) coverage. Peak SNR/CNR was 57.6 +/- 22.0/37.5 +/- 19.7 over all segments in the first eight slices.<h4>Conclusion</h4>3D performed better than 2D multi-slice MPI in estimating the size of perfusion defects in phantoms. Highly accelerated 3D MPI at 3T was feasible in volunteers, allowing whole LV coverage with excellent image quality and high SNR/CNR.
Project description:BACKGROUND:Hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) are both associated with an increased left ventricular (LV) wall thickness. Whilst LV ejection fraction is frequently normal in both, LV strain assessment could differentiate between the diseases. We sought to establish if cardiovascular magnetic resonance myocardial feature tracking (CMR-FT), an emerging method allowing accurate assessment of myocardial deformation, differentiates between both diseases. Additionally, CMR assessment of fibrosis and LV hypertrophy allowed association analyses and comparison of diagnostic capacities. METHODS:Two-hundred twenty-four consecutive subjects (53 HHD, 107 HCM, and 64 controls) underwent 1.5T CMR including native myocardial T1 mapping and late gadolinium enhancement (LGE). Global longitudinal strain (GLS) was assessed by CMR-FT (CVi42, Circle Cardiovascular Imaging Inc.). RESULTS:GLS was significantly higher in HCM patients (-14.7±3.8 vs. -16.5±3.3% [HHD], P = 0.004; or vs. -17.2±2.0% [controls], P<0.001). GLS was associated with LV mass index (HHD, R = 0.419, P = 0.002; HCM, R = 0.429, P<0.001), and LV ejection fraction (HHD, R = -0.493, P = 0.002; HCM, R = -0.329, P<0.001). In HCM patients, GLS was also associated with global native T1 (R = 0.282, P = 0.003), and LGE volume (? = 0.380, P<0.001). Discrimination between HHD and HCM by GLS (c = 0.639, 95% confidence interval [CI] 0.550-0.729) was similar to LV mass index (c = 0.643, 95% CI 0.556-0.731), global myocardial native T1 (c = 0.718, 95% CI 0.638-0.799), and LGE volume (c = 0.680, 95% CI 0.585-0.775). CONCLUSION:CMR-FT GLS differentiates between HHD and HCM. In HCM patients GLS is associated with myocardial fibrosis. The discriminatory capacity of CMR-FT GLS is similar to LV hypertrophy and fibrosis imaging markers.
Project description:The left ventricular (LV) remodeling process associated with significant valvular heart disease (VHD) is characterized by an increase of myocardial interstitial space with deposition of collagen and loss of myofibers. These changes occur before LV systolic function deteriorates or the patient develops symptoms. Cardiovascular magnetic resonance (CMR) permits assessment of reactive fibrosis, with the use of T1 mapping techniques, and replacement fibrosis, with the use of late gadolinium contrast enhancement. In addition, functional consequences of these structural changes can be evaluated with myocardial tagging and feature tracking CMR, which assess the active deformation (strain) of the LV myocardium. Several studies have demonstrated that CMR techniques may be more sensitive than the conventional measures (LV ejection fraction or LV dimensions) to detect these structural and functional changes in patients with severe left-sided VHD and have shown that myocardial fibrosis may not be reversible after valve surgery. More important, the presence of myocardial fibrosis has been associated with lesser improvement in clinical symptoms and recovery of LV systolic function. Whether assessment of myocardial fibrosis may better select the patients with severe left-sided VHD who may benefit from surgery in terms of LV function and clinical symptoms improvement needs to be demonstrated in prospective studies. The present review article summarizes the current status of CMR techniques to assess myocardial fibrosis and appraises the current evidence on the use of these techniques for risk stratification of patients with severe aortic stenosis or regurgitation and mitral regurgitation.
Project description:BACKGROUND:Stress 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. METHODS:In 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. RESULTS:13 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. CONCLUSION:20.6% 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.
Project description:BACKGROUND:Preliminary semi-quantitative cardiovascular magnetic resonance (CMR) perfusion studies have demonstrated reduced myocardial perfusion reserve (MPR) in patients with angina and risk factors for microvascular disease (MVD), however fully quantitative CMR has not been studied. The purpose of this study is to evaluate whether fully quantitative CMR identifies reduced MPR in this population, and to investigate the relationship between epicardial atherosclerosis, left ventricular hypertrophy (LVH), extracellular volume (ECV), and perfusion. METHODS:Forty-six patients with typical angina and risk factors for MVD (females, or males with diabetes or metabolic syndrome) who had no obstructive coronary artery disease by coronary angiography and 20 healthy control subjects underwent regadenoson stress CMR perfusion imaging using a dual-sequence quantitative spiral pulse sequence to quantify MPR. Subjects also underwent T1 mapping to quantify ECV, and computed tomographic (CT) coronary calcium scoring to assess atherosclerosis burden. RESULTS:In patients with risk factors for MVD, both MPR (2.21 [1.95,2.69] vs. 2.93 [2.763.19], p?<?0.001) and stress myocardial perfusion (2.65?±?0.62 ml/min/g, vs. 3.17?±?0.49 ml/min/g p?<?0.002) were reduced as compared to controls. These differences remained after adjusting for age, left ventricular (LV) mass, body mass index (BMI), and gender. There were no differences in native T1 or ECV between subjects and controls. CONCLUSIONS:Stress myocardial perfusion and MPR as measured by fully quantitative CMR perfusion imaging are reduced in subjects with risk factors for MVD with no obstructive CAD as compared to healthy controls. Neither myocardial hypertrophy nor fibrosis accounts for these differences.