BackgroundWomen with SLE have an elevated risk of cardiovascular disease. Many women with SLE frequently report chest pain in the absence of obstructive coronary artery disease (CAD) due to coronary ...microvascular dysfunction (CMD), a form of ischemia with no obstructive CAD (Manchanda et al, 2022). Echocardiographic studies have shown that SLE patients have reduced left ventricular (LV) function, which may also correlate with higher SLE disease activity scores (Gegenava et al, 2020). As such, we used cardiac magnetic resonance imaging (cMRI) to investigate the relationship between SLE, related inflammatory biomarkers, and cardiac function in female SLE patients.MethodsWe performed stress cMRI in women with SLE and chest pain with no obstructive CAD (n=13, all met ACR 1997 criteria, table 1) and reference controls (n=22) using our published protocol (Aldiwani et al, 2022). We evaluated LV function, tissue characterization (T1 mapping, ECV), and delayed enhancement, using CV142 software (Circle Cardiovascular Imaging Inc, Calgary, AB, Canada). Myocardial perfusion reserve index (MPRI) was calculated using our published protocol (Thomson et al, 2015). SLEDAI and SLICC Damage Index (DI) were calculated per validated criteria (Bombardier et al, 1992, Gladman et al, 1997). Serum samples were analyzed for inflammatory markers and autoantibodies (table 1). Independent two-tailed t test was performed on clinical values with CMD and no CMD SLE subjects, and on cMRI values with all SLE subjects and controls. Correlation analysis was done on clinical values, and cMRI values on all SLE subjects.ResultsOverall, 40% of SLE subjects had MPRI values < 1.84, consistent with CMD. Compared to controls, SLE subjects had significantly lower LVEF, and higher LVESVi and LVMi (table 2). Corresponding to this, radial, longitudinal, and circumferential strain were significantly lower in the SLE subjects. In correlation analysis of serum inflammatory biomarkers to cMRI values in the SLE subjects, SLICC DI was related to worse cardiac function (lower radial, circumferential and longitudinal strain) and higher T1 time (table 3).Additionally, fasting insulin and ESR were negatively correlated with LVMi. Fasting insulin also negatively correlated with ECV. CRP had a positive association with LVESV index and CI and a negative association with longitudinal strain.ConclusionsAmong women with SLE with chest pain and no obstructive CAD, 40% have CMD. While evaluations of known inflammatory markers (such as CRP and ESR) predictably correlated with decreased cardiac function (Jha et al, 2022), our study found that decreased fasting insulin levels as a novel marker of diminished LV function. In addition, although studies have used SLEDAI as a marker of disease activity in cardiac dysfunction, we are the first to demonstrate that SLICC DI, an assessment of SLE damage, is also correlated with cardiac dysfunction in SLE. This indicates that SLE patients with higher SLICC DI and increased SLE-related damage could potentially have silent involvement in their cardiac tissue, and as such using SLICC DI is another tool that should be used to evaluate the association between SLE and LV dysfunction. 694Abstract 904 Table 1Baseline characteristics of female SLE participants. There were no group difference in clinical and laboratory values in the SLE participants with and without CMD. Complement 3 (C3); Complement 4 (C4); Erythrocyte Sedimentation Rate (ESR); C-Reactive Protein (CRP); Antinuclear antibody (ANA); Ribonucleoprotein (RNP); Smith (Sm); Anti- topoisomerase I antibody (Scl-70). Mean ±SD range SLE patients (n=13) CMD (n=5) No CMD (n=8) P values Age 46 ± 6 years 43 37–51 years 48 43–57 years NS SLICC 1.9 ± 2.5 2.8 ± 3 0–6 1.4 ± 2 0–6 NS SLEDAI 0.5 ± 1 0.8 ± 0.8 0–2 0.4 ± 1 0–3 NS Clinical Labs Fasting Blood Sugar(mg/dl) 77.6 ± 8.6 80.2 ± 6.5 72–90 75.5 ± 10.1 65–91 NS Fasting Insulin (mIU/ml) 9.2 ± 11.3 14.8 ± 15.4 2–42 4.5 ± 2.5 1.4–7.6 NS Serum Creatinine (mg/dL) 0.70 ± 0.08 0.67 ± 0.12 0.55–0.84 0.72 ± 0.03 0.66–0.76 NS Serum Protein (g/dL) 7.29 ± 0.96 7.58 ± 1.47 6.4–10.1 7.09 ± 0.40 6.8–7.9 NS C3 (mg/dL) 114 ± 30 124 ± 34 81–153 108 ± 26 77–156 NS C4 (mg/dL) 26 ± 12 20 ± 11 10–32 29 ± 12 22–51 NS ESR (mm/hr) 20.5 ± 20.5 32 ± 24 16–73 14 ± 16 1–47 NS CRP (mg/dL) 3.2 ± 4.8 2.6 ± 2.2 0.4–5.4 3.6 ± 6.0 0.2–17.9 NS Anti-ANA 434 ± 273 424 ± 299 50–640 440 ± 277 80–640 NS Anti-DNA <10 <10 <10 — RNP Antibody 42.3 ± 58 68 ± 70.4 2–156 26.3 ± 46.8 2–133 NS Anti-Sm 13.9 ± 18.7 17.2 ± 20.6 2–52 11.9 ± 18.6 1–51 NS SSA (Ro) 22.8 ± 38.6 42.8 ± 55 2–104 10.4 ± 19.2 1–56 NS SSB (La) 12.2 ± 28.4 22.8 ± 45.5 2–104 5.5 ± 8.3 1–25 NS Anti-Scl 6 ± 7 4.2 ± 3.3 2–10 1 ± 25 1–25 NS Abstract 904 Table 2Comparison of cardiac MRI analysis between SLE participants and reference controls (RC). Left Ventricular (LV) End Diastolic Volume (LVEDV); LV End Systolic Volume (LVESV); LV Systolic Volume (LVSV); Ejection Fraction (EF); LV Mass (LVM); LV End Systolic Diameter (LVESD); Body Surface Area (BSA); LVEDV/BSA (LVEDV index); LVESV/BSA (LVESV index); LVSV/BSA (LVSV index); LVM/BSA (LVM index); CO/BSA (cardiac index), Extracellular Volume Fraction (ECV). Variable SLE (n=13) RC (n=22) p-value LVEDV (ml) 127 ± 34 114 ± 18 NS LVESV (ml) 53 ± 20 42 ± 10 0.0339 LVSV (ml) 75 ± 18 73 ± 10 NS EF (%) 59 ± 7 64 ± 5 0.0242 LVM/LVESD (g/dL) 0.66 ± 0.08 0.62 ± 0.07 NS LVEDV/BSA (LVEDVi, mL/m2) 72.02 ± 15.4 67.40 ± 9.3 NS LVESV/BSA (LVESVi, mL/m2) 29.9 ± 10.2 24.5 ± 5.6 0.0481 LVSV/BSA (LVSVi, mL/m2) 42.56 ± 8.2 42.92 ± 5.4 NS LVM/BSA (LVMi, g/m2) 47.31 ± 9.3 41.34 ± 4.3 0.0141 CO/BSA (CI, L/min/m2) 3 ± 1 2.6 ± 0.3 NS LVM (g) 83 ± 20 70 ± 9 0.0119 Radial Strain 29.70 ± 6.2 34.37 ± 5.8 0.0306 Circumferential Strain -17.94 ± 2.5 -19.73 ± 2 0.0251 Longitudinal Strain -18.40 ± 2.2 -20.10 ± 1.9 0.0202 T1 1263 ± 35 1259 ± 56 (n=11) NS ECV 29 ± 3 29.3 ± 2.3 (n=11) NS Abstract 904 Table 3Correlation analysis of cardiac function versus clinical values from SLE participants in the study. The Spearman r coefficient and p value (p) is shown. LVESV: left ventricular end-systolic volume; LVEDV: left ventricular end-diastolic volume; LVSV: left ventricular systolic volume; EF: ejection fraction; LVM: left ventricular mass; BSA: body surface area; ECV: extracellular volume.
It has recently been shown that magnetic resonance (MR) “native T1” mapping is capable of characterizing abnormal microcirculation in patients with obstructive coronary artery disease (CAD). In ...studies involving women with signs and symptoms of ischemia and no obstructive CAD (INOCA), however, the potential role of native T1 as an imaging marker and its association with indices of diastolic function or vasodilator-induced myocardial ischemia have not been explored. We investigated whether native T1 in INOCA is associated with reduced myocardial perfusion reserve index (MPRI) or with diastolic dysfunction.
Twenty-two female patients with INOCA and twelve female reference controls with matching age and body-mass index were studied. The patients had evidence of vasodilator-induced ischemia without obstructive CAD or any prior infarction. All 34 subjects underwent stress/rest MR including native T1 mapping (MOLLI 5(3)3) at 1.5-Tesla.
Compared with controls, patients had similar morphology/function. As expected, MPRI was significantly reduced in patients compared to controls (1.78 ± 0.39 vs. 2.49 ± 0.41, p < 0.0001). Native T1 was significantly elevated in patients (1040.1 ± 29.3 ms vs. 1003.8 ± 18.5 ms, p < 0.001) and the increased T1 showed a significant inverse correlation with MPRI (r = −0.481, p = 0.004), but was not correlated with reduced diastolic strain rate.
Symptomatic women with INOCA have elevated native T1 compared to matched reference controls and there is a significant association between elevated native T1 and impaired MPRI, considered a surrogate measure of ischemia severity in this cohort. Future studies in a larger cohort are needed to elucidate the mechanism underlying this inverse relationship.
•Women with signs and symptoms of myocardial ischemia and no obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction.•In this pilot study, native T1 was significantly elevated in INOCA patients compared to matched reference controls.•The increased native T1 showed a significant inverse correlation with myocardial perfusion reserve index.•Native myocardial T1 may evolve as a useful imaging marker in serial studies of INOCA patients.
This expert consensus statement from the Society of Cardiovascular Computed Tomography (SCCT) provides an evidence synthesis on the use of computed tomography (CT) imaging for diagnosis and risk ...stratification of coronary artery disease in women. From large patient and population cohorts of asymptomatic women, detection of any coronary artery calcium that identifies females with a 10-year atherosclerotic cardiovascular disease risk of >7.5% may more effectively triage women who may benefit from pharmacologic therapy. In addition to accurate detection of obstructive coronary artery disease (CAD), CT angiography (CTA) identifies nonobstructive atherosclerotic plaque extent and composition which is otherwise not detected by alternative stress testing modalities. Moreover, CTA has superior risk stratification when compared to stress testing in symptomatic women with stable chest pain (or equivalent) symptoms. For the evaluation of symptomatic women both in the emergency department and the outpatient setting, there is abundant evidence from large observational registries and multi-center randomized trials, that CT imaging is an effective procedure. Although radiation doses are far less for CT when compared to nuclear imaging, radiation dose reduction strategies should be applied in all women undergoing CT imaging. Effective and appropriate use of CT imaging can provide the means for improved detection of at-risk women and thereby focus preventive management resulting in long-term risk reduction and improved clinical outcomes.
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 ± 15.3 years. 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.
To date, the therapeutic benefit of revascularization vs. medical therapy for stable individuals undergoing invasive coronary angiography (ICA) based upon coronary computed tomographic angiography ...(CCTA) findings has not been examined.
We examined 15 223 patients without known coronary artery disease (CAD) undergoing CCTA from eight sites and six countries who were followed for median 2.1 years (interquartile range 1.4-3.3 years) for an endpoint of all-cause mortality. Obstructive CAD by CCTA was defined as a ≥50% luminal diameter stenosis in a major coronary artery. Patients were categorized as having high-risk CAD vs. non-high-risk CAD, with the former including patients with at least obstructive two-vessel CAD with proximal left anterior descending artery involvement, three-vessel CAD, and left main CAD. Death occurred in 185 (1.2%) patients. Patients were categorized into two treatment groups: revascularization (n = 1103; 2.2% mortality) and medical therapy (n = 14 120, 1.1% mortality). To account for non-randomized referral to revascularization, we created a propensity score developed by logistic regression to identify variables that influenced the decision to refer to revascularization. Within this model (C index 0.92, χ2 = 1248, P < 0.0001), obstructive CAD was the most influential factor for referral, followed by an interaction of obstructive CAD with pre-test likelihood of CAD (P = 0.0344). Within CCTA CAD groups, rates of revascularization increased from 3.8% for non-high-risk CAD to 51.2% high-risk CAD. In multivariable models, when compared with medical therapy, revascularization was associated with a survival advantage for patients with high-risk CAD hazards ratio (HR) 0.38, 95% confidence interval 0.18-0.83, with no difference in survival for patients with non-high-risk CAD (HR 3.24, 95% CI 0.76-13.89) (P-value for interaction = 0.03).
In an intermediate-term follow-up, coronary revascularization is associated with a survival benefit in patients with high-risk CAD by CCTA, with no apparent benefit of revascularization in patients with lesser forms of CAD.
The prognostic value of coronary artery calcium (CAC) scoring is well established and has been suggested for use to exclude significant coronary artery disease (CAD) for symptomatic individuals with ...CAD. Contrast-enhanced coronary computed tomographic angiography (CCTA) is an alternative modality that enables direct visualization of coronary stenosis severity, extent, and distribution. Whether CCTA findings of CAD add an incremental prognostic value over CAC in symptomatic individuals has not been extensively studied.
We prospectively identified symptomatic patients with suspected but without known CAD who underwent both CAC and CCTA. Symptoms were defined by the presence of chest pain or dyspnoea, and pre-test likelihood of obstructive CAD was assessed by the method of Diamond and Forrester (D-F). CAC was measured by the method of Agatston. CCTAs were graded for obstructive CAD (>70% stenosis); and CAD plaque burden, distribution, and location. Plaque burden was determined by a segment stenosis score (SSS), which reflects the number of coronary segments with plaque, weighted for stenosis severity. Plaque distribution was established by a segment-involvement score (SIS), which reflects the number of segments with plaque irrespective of stenosis severity. Finally, a modified Duke prognostic index-accounting for stenosis severity, plaque distribution, and plaque location-was calculated. Nested Cox proportional hazard models for a composite endpoint of all-cause mortality and non-fatal myocardial infarction (D/MI) were employed to assess the incremental prognostic value of CCTA over CAC. A total of 8627 symptomatic patients (50% men, age 56 ± 12 years) followed for 25 months (interquartile range 17-40 months) comprised the study cohort. By CAC, 4860 (56%) and 713 (8.3%) patients had no evident calcium or a score of >400, respectively. By CCTA, 4294 (49.8%) and 749 (8.7%) had normal coronary arteries or obstructive CAD, respectively. At follow-up, 150 patients experienced D/MI. CAC improved discrimination beyond D-F and clinical variables (area under the receiver-operator characteristic curve 0.781 vs. 0.788, P = 0.004). When added sequentially to D-F, clinical variables, and CAC, all CCTA measures of CAD improved discrimination of patients at risk for D/MI: obstructive CAD (0.82, P < 0.001), SSS (0.81, P < 0.001), SIS (0.81, P = 0.003), and Duke CAD prognostic index (0.82, P < 0.0001).
In symptomatic patients with suspected CAD, CCTA adds incremental discriminatory power over CAC for discrimination of individuals at risk of death or MI.
The degree of stenosis on coronary CT angiography (CCTA) guides referral for CT-derived flow reserve (FFRct). We sought to assess whether semiquantitative assessment of high-risk plaque (HRP) ...features on CCTA improves selection of studies for FFRct over stenosis assessment alone.
Per-vessel FFRct was computed in 1,395 vessels of 836 patients undergoing CCTA with 25–99% maximal stenosis. By consensus analysis, stenosis severity was graded as 25–49%, 50–69%, 70–89%, and 90–99%. HRPs including low attenuation plaque (LAP), positive remodeling (PR), and spotty calcification (SC) were assessed in lesions with maximal stenosis. Lesion FFRct was measured distal to the lesion with maximal stenosis, and FFRct<0.80 was defined as abnormal. Association of HRP and abnormal lesion FFRct was evaluated by univariable and multivariable logistic regression models.
The frequency of abnormal lesion FFRct increased with increase of stenosis severity across each stenosis category (25–49%:6%; 50–69%:30%; 70–89%:54%; 90–99%:91%, p < 0.001). Univariable analysis demonstrated that stenosis severity, LAP, and PR were predictive of abnormal lesion FFRct, while SC was not. In multivariable analyses considering stenosis severity, presence of PR, LAP, and PR and/or LAP were independently associated with abnormal FFRct: Odds ratio 1.58, 1.68, and 1.53, respectively (p < 0.02 for all). The presence of PR and/or LAP increased the frequency of abnormal FFRct with mild stenosis (p < 0.05) with a similar trend with 70–89% stenosis. The combination of 2 HRP (LAP and PR) identified more lesions with FFR < 0.80 than only 1 HRP.
Semiquantitative visual assessment of high-risk plaque features may improve the selection of studies for FFRct.
Stress imaging has been the standard for diagnosing functionally significant coronary artery disease. It is unknown whether novel, atherosclerotic plaque measures improve accuracy beyond coronary ...stenosis for diagnosing invasive fractional flow reserve (FFR) measurement.
To compare the diagnostic accuracy of comprehensive anatomic (obstructive and nonobstructive atherosclerotic plaque) vs functional imaging measures for estimating vessel-specific FFR.
Controlled clinical trial of diagnostic accuracy with a multicenter derivation-validation cohort of patients referred for nonemergent invasive coronary angiography. A total of 612 patients (64 10 years; 30% women) with signs and symptoms suggestive of myocardial ischemia from 23 sites were included. Patients were recruited from 2014 to 2017. Data analysis began in August 2018.
Patients underwent invasive coronary angiography with measurement of invasive FFR, coronary computed tomographic angiography (CCTA) quantification of atherosclerotic plaque and FFR by CT (FFR-CT), and semiquantitative scoring of rest/stress myocardial perfusion imaging (by magnetic resonance, positron emission tomography, or single photon emission CT). Multivariable generalized linear mixed models were derived and validated calculating the area under the receiver operating characteristics curve.
The primary end point was invasive FFR of 0.80 or less.
Of the 612 patients, the mean (SD) age was 64 (10) years, and 426 (69.9%) were men. An invasive FFR of 0.80 or less was measured in 26.5% of 1727 vessels. In the derivation cohort, CCTA vessel-specific factors associated with FFR 0.80 or less were stenosis severity, percentage of noncalcified atheroma volume, lumen volume, the number of lesions with high-risk plaque (≥2 of low attenuation plaque, positive remodeling, napkin ring sign, or spotty calcification), and the number of lesions with stenosis greater than 30%. Fractional flow reserve-CT was not additive to this model including stenosis and atherosclerotic plaque. Significant myocardial perfusion imaging predictors were the summed rest and difference scores. In the validation cohort, the areas under the receiver operating characteristic curve were 0.81 for CCTA vs 0.67 for myocardial perfusion imaging (P < .001).
A comprehensive anatomic interpretation with CCTA, including quantification of obstructive and nonobstructive atherosclerotic plaque, was superior to functional imaging in the diagnosis of invasive FFR. Comprehensive CCTA measures improve prediction of vessel-specific coronary physiology more so than stress-induced alterations in myocardial perfusion.
ClinicalTrials.gov Identifier: NCT02173275.
Distinct histopathologic changes occur in acute cellular rejection (ACR), antibody‐mediated rejection (AMR), and biopsy‐negative rejection (BNR). Cardiovascular magnetic resonance (CMR)‐based ...myocardial tissue characterization can be used to quantify these changes. We assessed T1, T2, and extracellular volume fraction (ECV) by CMR in patients with subtypes of rejection. T1, T2, and ECV were quantified at the mid‐ventricular level and compared between patients with and without rejection. The association between quantitative tissue characteristics and the combined outcome of death, retransplantation, heart failure hospitalization, or myocardial infarction was evaluated with a Cox‐proportional hazards model. In 46 patients, mean age 53.3 ± 13.7 years, 71.7% male, at a median of 7.4 years from transplant, average myocardial T1 was increased in BNR compared with no rejection (1057 vs 1012 msec, P = .006). Average myocardial T2 was elevated in all types of rejection, P < .05. In a cox‐proportional hazards model, higher T2 values were associated with an increase in the combined clinical outcome (adjusted HR 1.21, 95% CI 1.06‐1.37, P = .004) after adjusting for left ventricular mass index. Myocardial tissue characteristics are abnormal in all subtypes of rejection, and abnormal T2 quantified by CMR provides additional prognostic value.
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