Lower Myocardial Perfusion Reserve 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.

Impact of diabetes on remodelling, microvascular function and exercise capacity in aortic stenosis

ObjectiveTo characterise cardiac remodelling, exercise capacity and fibroinflammatory biomarkers in patients with aortic stenosis (AS) with and without diabetes, and assess the impact of diabetes on outcomes.MethodsPatients with moderate or...

Fully automated pixel-wise quantitative CMR-myocardial perfusion with CMR-coronary angiography to detect hemodynamically significant coronary artery disease.

We applied a fully automated pixel-wise post-processing framework to evaluate fully quantitative cardiovascular magnetic resonance myocardial perfusion imaging (CMR-MPI). In addition, we aimed to evaluate the additive value of coronary magnetic resonance angiography (CMRA) to the diagnostic performance of fully automated pixel-wise quantitative CMR-MPI for detecting hemodynamically significant coronary artery disease (CAD). A total of 109 patients with suspected CAD were prospectively enrolled and underwent stress and rest CMR-MPI, CMRA, invasive coronary angiography (ICA), and fractional flow reserve (FFR). CMRA was acquired between stress and rest CMR-MPI acquisition, without any additional contrast agent. Finally, CMR-MPI quantification was analyzed by a fully automated pixel-wise post-processing framework. Of the 109 patients, 42 patients had hemodynamically significant CAD (FFR ≤ 0.80 or luminal stenosis ≥ 90% on ICA) and 67 patients had hemodynamically non-significant CAD (FFR ˃ 0.80 or luminal stenosis < 30% on ICA) were enrolled. On the per-territory analysis, patients with hemodynamically significant CAD had higher myocardial blood flow (MBF) at rest, lower MBF under stress, and lower myocardial perfusion reserve (MPR) than patients with hemodynamically non-significant CAD (p < 0.001). The area under the receiver operating characteristic curve of MPR (0.93) was significantly larger than those of stress and rest MBF, visual assessment of CMR-MPI, and CMRA (p < 0.05), but similar to that of the integration of CMR-MPI with CMRA (0.90). Fully automated pixel-wise quantitative CMR-MPI can accurately detect hemodynamically significant CAD, but the integration of CMRA obtained between stress and rest CMR-MPI acquisition did not provide significantly additive value. • Full quantification of stress and rest cardiovascular magnetic resonance myocardial perfusion imaging can be postprocessed fully automatically, generating pixel-wise myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) maps. • Fully quantitative MPR provided higher diagnostic performance for detecting hemodynamically significant coronary artery disease, compared with stress and rest MBF, qualitative assessment, and coronary magnetic resonance angiography (CMRA). • The integration of CMRA and MPR did not significantly improve the diagnostic performance of MPR alone.

Association of hepatic steatosis with subclinical cardiac dysfunction in asymptomatic people with type 2 diabetes

Abstract Introduction Non-alcoholic fatty liver disease is highly prevalent among people with type 2 diabetes (T2D) and is an emerging risk factor for heart failure with preserved ejection fraction (HFpEF). Whether excess liver adiposity is simply a marker of the coexisting adverse cardiometabolic risk profile or independently contributes to the development of HFpEF is unclear. Purpose To assess the association between liver fat fraction and subclinical cardiac dysfunction in adults with T2D. Methods Prospective cross-sectional study. Two-hundred and thirty-eight adults with T2D (mean age 63±7 years, 62% males, HbA1c 7.2±1.5%, diabetes duration 10±8 years) with no signs, symptoms, or evidence of cardiovascular disease and 40 age-, sex-, and ethnicity-matched non-diabetic controls (mean age 61±8 years, 63% males, HbA1c 5.2±1.2%) underwent comprehensive phenotyping with echocardiography and multiparametric cardiac MRI including adenosine stress and rest perfusion. Volumetric liver fat fraction (VLFF) was measured using a histologically validated, proprietary MRI technique blinded to all participant details. Inter-study reproducibility was assessed in participants (n=28) who underwent a repeat MRI within two weeks. Linear regression analysis was performed to assess any independent associations between VLFF and identified markers of subclinical cardiac dysfunction in subjects with T2D. Results People with T2D had evidence of concentric left ventricular (LV) remodelling (higher LV mass/volume), extracellular matrix expansion (higher ECV fraction), both systolic and diastolic dysfunction (lower global longitudinal systolic strain and E/A ratio, respectively), and coronary microvascular dysfunction (lower myocardial perfusion reserve) (Table 1). VLFF demonstrated excellent inter-study reproducibility with an intra-class correlation coefficient (ICC) of 0.988 (0.974–0.994). T2Ds had higher VLFF compared to controls [7.5 (3.8–13.7)% vs 2.9 (1.7–4.7)%, p&amp;lt;0.001]. In multivariable regression analysis adjusting for age, sex, ethnicity, body mass index, ambulatory systolic blood pressure, HbA1c, and low-density lipoprotein, VLFF (β=−0.161, p=0.027) was independently associated with E/A, but not other imaging measures of subclinical cardiac dysfunction. Conclusion Liver fat fraction is elevated in people with T2D and is independently associated with early LV diastolic dysfunction. These results add to the growing evidence that ectopic fat plays an important role in the pathogenesis of HFpEF and may be a potential target for intervention. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Institute for Health Research (NIHR) United Kingdom through a Research Professorship award (RP-2017-08-ST2-007).British Heart Foundation through a Clinical Research Training Fellowship (FS/16/47/32190).

Abstract 11702: Sex Differences in Diabetic Cardiomyopathy: Greater Reduction in Myocardial Perfusion Reserve in Women Than Men Driven by Increased Resting Perfusion

Introduction: Type 2 diabetes (T2D) confers a higher relative risk of heart failure in women than men. Women also have a greater prevalence of heart failure with preserved ejection fraction (HFpEF), linked to microvascular dysfunction. We hypothesize that sex-specific differences are present in the pathophysiological alterations of myocardial structure, function, and perfusion associated with T2D. Methods: Cross-sectional case-control study. Participants underwent comprehensive cardiac phenotyping with echocardiography and cardiac magnetic resonance with adenosine stress/rest perfusion. Global myocardial perfusion was derived as a mean of three short axis slices. Image analysis was performed by two observers blinded to all participant information. Statistical analysis was performed with independent-sample T-tests or Mann-Whitney test. Results: Individuals with T2D (n=287, 41% female) were compared with age-matched controls (n=87, 41% female). Women with T2D were more obese than men (body mass index 35.7±7.2 vs 32.4±5.3 kg/m 2 , p&lt;0.05). Both women and men with T2D had increased left ventricular (LV) concentric remodelling (greater LV mass/volume ratio), impaired diastolic (higher E/e’) and systolic (lower global longitudinal strain) function compared to controls. LV mass index was significantly increased in women only. Comparing T2D and controls, stress perfusion was not significantly different in both sexes whereas resting perfusion was increased in women (1.4±0.6 vs 1.0±0.4 ml/min/g, p&lt;0.05) but not in men. Consequently, women with T2D have a lower myocardial perfusion reserve than men (2.6±0.9 vs 3.1±0.9, p&lt;0.001). Conclusions: In asymptomatic people with T2D, women have increased LV mass index and lower myocardial perfusion reserve than men, driven primarily by increased resting perfusion. These findings support the growing evidence that microvascular dysfunction partly explains the greater risk of HFpEF in women with T2D.

Phenotyping hypertrophic cardiomyopathy using cardiac diffusion magnetic resonance imaging: the relationship between microvascular dysfunction and microstructural changes.

AimsMicrovascular dysfunction in hypertrophic cardiomyopathy (HCM) is predictive of clinical decline, however underlying mechanisms remain unclear. Cardiac diffusion tensor imaging (cDTI) allows in vivo characterization of myocardial microstructure by quantifying mean diffusivity (MD), fractional anisotropy (FA) of diffusion, and secondary eigenvector angle (E2A). In this cardiac magnetic resonance (CMR) study, we examine associations between perfusion and cDTI parameters to understand the sequence of pathophysiology and the interrelation between vascular function and underlying microstructure.Methods and resultsTwenty HCM patients underwent 3.0T CMR which included: spin-echo cDTI, adenosine stress and rest perfusion mapping, cine-imaging, and late gadolinium enhancement (LGE). Ten controls underwent cDTI. Myocardial perfusion reserve (MPR), MD, FA, E2A, and wall thickness were calculated per segment and further divided into subendocardial (inner 50%) and subepicardial (outer 50%) regions. Segments with wall thickness ≤11 mm, MPR ≥2.2, and no visual LGE were classified as ‘normal’. Compared to controls, ‘normal’ HCM segments had increased MD (1.61 ± 0.09 vs. 1.46 ± 0.07 × 10−3 mm2/s, P = 0.02), increased E2A (60 ± 9° vs. 38 ± 12°, P < 0.001), and decreased FA (0.29 ± 0.04 vs. 0.35 ± 0.02, P = 0.002). Across all HCM segments, subendocardial regions had higher MD and lower MPR than subepicardial (MDendo 1.61 ± 0.08 × 10−3 mm2/s vs. MDepi 1.56 ± 0.18 × 10−3 mm2/s, P = 0.003, MPRendo 1.85 ± 0.83, MPRepi 2.28 ± 0.87, P < 0.0001).ConclusionIn HCM patients, even in segments with normal wall thickness, normal perfusion, and no scar, diffusion is more isotropic than in controls, suggesting the presence of underlying cardiomyocyte disarray. Increased E2A suggests the myocardial sheetlets adopt hypercontracted angulation in systole. Increased MD, most notably in the subendocardium, is suggestive of regional remodelling which may explain the reduced subendocardial blood flow.

Prognostic value of pericoronary adipose tissue and coronary vascular function by cardiac 82Rb PET/CT imaging in patients with suspected coronary artery disease and normal myocardial perfusion imaging

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Pericoronary adipose tissue, due to its proximity to coronary arteries, has been proposed contribute to the progression of coronary atherosclerosis. Purpose The aim of this study was to evaluate the prognostic value of pericoronary fat thickness (PCFT), coronary artery calcium (CAC) score and myocardial perfusion reserve (MPR) by hybrid 82Rubidium (82Rb) PET/CT imaging in patients with suspected coronary artery disease (CAD) and normal myocardial perfusion imaging (MPI). Methods A total of 640 patients without overt CAD and with normal rest-stress 82Rb PET/CT MPI were studied. PCFT was calculated on CT images as the maximum fat thickness (mm) between heart surface and visceral epicardium surrounding the main coronary arteries. CAC score was categorized as 0, &amp;lt;400 or ≥400. MPR was considered reduced when &amp;lt;2. Endpoints events were cardiac death, nonfatal myocardial infarction and coronary revascularization. Results During a follow-up of 42 ± 13 months, 29 events occurred (cumulative event rate 5%). Patients with events were older (66 ± 13 vs. 60 ± 13 years, p &amp;lt; 0.01), had higher PCFT (13 ± 2 vs 11 ± 2 mm, p &amp;lt; 0.001), higher prevalence of CAC score ≥400 (48% vs. 21%, p &amp;lt; 0.01), and lower MPR (2.1 ± 0.7 vs. 2.7 ± 0.7, p &amp;lt; 0.001) compared to those without. A higher prevalence of MPR &amp;lt;2 was observed in patients with events (48% vs. 18, p &amp;lt; 0.001) compared to those without. Patients with reduced MPR had higher PCFT compared to those with normal MPR (12 ± 2 vs. 11 ± 1 mm, p &amp;lt; 0.01). A PCFT value of 11.2 mm was the best trade-off between sensitivity and specificity to detect a reduced MPR. Event rate was higher in patients above this threshold compared to those below (8% vs. 1.5%, p &amp;lt; 0.001). At Cox univariate analysis, age (p &amp;lt; 0.05), PCFT &amp;gt;11.2 mm (p &amp;lt; 0.001), CAC score ≥400 (p &amp;lt; 0.01), and MPR &amp;lt;2 (p &amp;lt; 0.001) were predictors of events. At multivariate analysis, only PCFT &amp;gt;11.2 mm and MPR &amp;lt;2 were independent predictors of events (both p &amp;lt; 0.01). At incremental analysis, adding PCFT &amp;gt;11.2 to a model including clinical data and MPR &amp;lt;2 increased the global chi-square from 26 to 35 (p &amp;lt; 0.01). Classification tree analysis produced 3 terminal groups. For patients with MPR &amp;lt;2, no further split was needed (event rate 12% vs. 3%, p &amp;lt; 0.001). On the contrary, patients with MPR ≥2 were further stratified by PCFT (event rate 7% in patients with and 0.3% in those without (p &amp;lt; 0.001) PCFT &amp;gt;11.2. Conclusions In patients with suspected CAD and normal stress MPI, coronary vascular dysfunction and high PCFT are associated with increased cardiac risk. PCFT could help in identifying patients at higher risk of events. Combined evaluation of anatomical and functional vascular abnormalities by 82Rb PET/CT might allow a better risk stratification.

Coronary vascular function in patients with resistant hypertension and normal myocardial perfusion: a propensity score analysis.

Impaired myocardial perfusion reserve (MPR) may occur earlier than coronary atherosclerosis and it may be an early manifestation of developing coronary artery disease (CAD) in patients with resistant hypertension (RH). We evaluated the relationship between RH and MPR in patients with systemic arterial hypertension after balancing for coronary risk factors. We studied 360 subjects without overt CAD and normal myocardial perfusion at stress-rest 82Rb positron emission tomography/computed tomography. To account for differences in baseline characteristics between patients with resistant and controlled hypertension, we created a propensity score-matched cohort considering clinical variables and coronary risk factors. Before matching, patients with RH were significantly older, had higher prevalence of male gender and hypercholesterolaemia, and showed significantly lower global hyperaemic myocardial blood flow (MBF) and MPR compared with those with controlled hypertension, while baseline MBF and coronary artery calcium (CAC) content were similar in both groups. After matching, there were no significant differences in clinical variables and coronary risk factors between patients with resistant and controlled hypertension, but patients with RH still had lower hyperaemic MBF and MPR (both P < 0.001). At univariable and multivariable linear regression analyses, age, RH, and CAC resulted significant predictors of lower MPR values (all P < 0.05). After balancing clinical characteristic by propensity score analysis, patients with RH had a blunted hyperaemic MBF and MPR compared with patients with controlled hypertension. The identification of impaired MPR could help to identify early structural alterations of the arterial walls in patients with RH.

113 Novel diagnostic criterion for microvascular ischaemia using cmr perfusion imaging: validation against invasive index of microvascular resistance

BackgroundIn over 50% of patients with angina, the underlying ischaemia is related to microvascular dysfunction (MVD), rather than epicardial coronary artery disease (CAD). Clinically, MVD remains a major diagnostic challenge,...

88 Characterisation of Sub-clinical Primary Myocardial Disease in Systemic Sclerosis – Preliminary Findings from a Cardiac Magnetic Resonance Study

<h3>Background</h3> Systemic sclerosis (SSc) is a chronic disease characterised by systemic inflammation, vasculopathy and fibrosis. Primary myocardial disease occurs in both limited (lcSSc) and diffuse (dcSSc) cutaneous subtypes, and carries a poor prognosis. The natural history is poorly understood, with no clear approach to identifying the ‘at-risk’ patient. CMR studies in SSc have rarely correlated with disease phenotype. <h3>Objectives</h3> To determine cardiovascular manifestations of SSc using multi-component CMR. <h3>Method</h3> Eleven patients fulfilling SSc ACR/Le-Roy criteria, without known CV disease or diabetes, underwent CMR at 3.0T (Philips Achieva TX). Data from 10 healthy subjects served as a control group. Standard bSSFP cine images were acquired and LV dimensions calculated. First-pass perfusion imaging in three short-axis LV slices was performed during administration of 0.1 mmol/kg of gadobutrol at 3 min of 140 mcg/kg/min adenosine for stress and repeated 15 min later at rest. Myocardial perfusion reserve (MPR) was calculated using Fermi deconvolution (PMI v.0.4, [Sourbron, 2009] with basal blood pool providing the arterial input. Native and 15 min post final contrast T1 maps were generated from mid-LV short axis using a modified 3,3,5 Look-Locker inversion sequence to calculate extra-cellular volume (ECV) fraction. <h3>Results</h3> Patient characteristics were as follows: Mean age 54 ± 16, disease duration 9.6 ± 7.3 years, 7 female, 7 lcSSc subtype, 4 dcSSc subtype, 5 interstitial lung disease. Smoking status: 1 current, 8 ex-smoker, 2 never. 3 have known hypertension. CMR measurements are presented in Table 1. One patient with lsSSc subtype showed lateral mid-ventricular wall enhancement on LGE. ECV increased and MPR decreased with age (r = 0.657, p = 0.039; rho= -0.75, p = 0.02 respectively). A non-significant trend for a higher ECV was noted in lcSSc subtype (mean ECV 33% vs. 28% dcSSc subtype, p = 0.14). ECV was similar for disease duration (mean ECV 33% &gt;10 years vs. 30% &lt;10 years, p = 0.2). MPR was non-significantly lower in lcSSc subtype (mean 1.83 vs. 2.13 in dcSSc subtype, p = 0.3) and there was no strong association with disease duration. MPR in SSc was lower than in healthy controls (n = 9) (1.9 vs. 2.8, p = 0.03). <h3>Conclusion</h3> CMR demonstrates lower MPR in patients with SSc than in controls. Our preliminary data suggest that quantitative CMR may also be able to detect differences in myocardial involvement in subtypes of the disease, justifying future larger studies.

Comparison of Magnetic Resonance Perfusion Imaging Versus Invasive Fractional Flow Reserve for Assessment of the Hemodynamic Significance of Epicardial Coronary Artery Stenosis

This study evaluated whether first-pass perfusion cardiovascular magnetic resonance (FP-CMR) could predict the hemodynamic significance of epicardial coronary artery stenosis as defined by invasively determined fractional flow reserve at coronary angiography. In 19 patients with known coronary artery disease (CAD), the hemodynamic relevance of 22 stenoses (mean angiographic severity 73 +/- 9%) was determined using fractional flow reserve measurements (cutoff 0.75). Results were compared with a territorial index of myocardial perfusion reserve (MPR) derived from FP-CMR. In addition, 9 age-matched patients with low prevalence of risk factors and without CAD at angiography served as a control group. A cutoff of 1.5 for MPR separated hemodynamically relevant from nonrelevant stenoses with a sensitivity and specificity of 92% and 92%, respectively. The area under the receiver-operator characteristic curve was 0.97. In the patient group, territories supplied by arteries without significant stenosis (<or=50%) showed a lower MPR compared with the control group (p <0.0001), suggesting the presence of microvascular dysfunction. In conclusion, FP-CMR may be useful for assessment of the hemodynamic relevance of angiographically undetermined CAD.

Lower Myocardial Perfusion Reserve Is Associated With Decreased Regional Left Ventricular Function in Asymptomatic Participants of the Multi-Ethnic Study of Atherosclerosis

Myocardial ischemia is an important determinant of regional left ventricular systolic function. Myocardial blood flow reserve may be impaired by cardiovascular disease before alterations of myocardial perfusion at rest become manifest. Nevertheless, the relation between flow reserve and regional myocardial function has not been studied in individuals without a history of clinical heart disease. Seventy-four participants (66+/-9 years, mean+/-SD) of the Multi-Ethnic Study of Atherosclerosis (MESA) underwent myocardial magnetic resonance tagging and contrast-enhanced perfusion studies. Regional myocardial function was evaluated as peak systolic circumferential strain (Ecc) in the three main coronary territories (left anterior descending [LAD], left circumflex, and right coronary artery [RCA]). Myocardial blood flow at rest and during adenosine-induced hyperemia was quantified by contrast-enhanced magnetic resonance imaging, to study the relation between regional flow and function after multivariable adjustment for age, gender, body mass index, left ventricular mass, and traditional risk factors. Lower regional myocardial blood flow during hyperemia was associated with reduced regional left ventricular function expressed as lower Ecc in the RCA (P<0.01) and left circumflex regions (P<0.05) measured in the subendocardium, mid-wall, and subepicardium. In contrast, no significant association was seen in the LAD territory (P=0.16). In addition, segmental function in LAD and RCA regions was reduced when individuals in the lowest 10th percentile for regional myocardial flow reserve were compared with the other participants. Absolute decreases in mid-wall Ecc LAD and RCA and global Ecc were 3.0%, 3.4%, and 2.8%, respectively (P<0.05 for all regions). Lower myocardial flow reserve is related to reduced regional function in asymptomatic individuals.