Circulating isomiRs May Be Superior Biomarkers Compared to Their Corresponding miRNAs: A Pilot Biomarker Study of Using isomiR-Ome to Detect Coronary Calcium-Based Cardiovascular Risk in Patients with NAFLD.

Circulating miRNAs are increasingly being considered as biomarkers in various medical contexts, but the value of analyzing isomiRs (isoforms of canonical miRNA sequences) has not frequently been assessed. Here we hypothesize that an in-depth analysis of the full circulating miRNA landscape could identify specific isomiRs that are stronger biomarkers, compared to their corresponding miRNA, for identifying increased CV risk in patients with non-alcoholic fatty liver disease (NAFLD)-a clinical unmet need. Plasma miRNAs were sequenced with next-generation sequencing (NGS). Liver fat content was measured with magnetic-resonance spectrometry (MRS); CV risk was determined, beyond using traditional biomarkers, by a CT-based measurement of coronary artery calcium (CAC) score and the calculation of a CAC score-based CV-risk percentile (CAC-CV%). This pilot study included n = 13 patients, age > 45 years, with an MRS-measured liver fat content of ≥5% (wt/wt), and free of overt CVD. NGS identified 1103 miRNAs and 404,022 different isomiRs, of which 280 (25%) and 1418 (0.35%), respectively, passed an abundance threshold. Eighteen (sixteen/two) circulating miRNAs correlated positively/negatively, respectively, with CAC-CV%, nine of which also significantly discriminated between high/low CV risk through ROC-AUC analysis. IsomiR-ome analyses uncovered 67 isomiRs highly correlated (R ≥ 0.55) with CAC-CV%. Specific isomiRs of miRNAs 101-3p, 144-3p, 421, and 484 exhibited stronger associations with CAC-CV% compared to their corresponding miRNA. Additionally, while miRNAs 140-3p, 223-3p, 30e-5p, and 342-3p did not correlate with CAC-CV%, specific isomiRs with altered seed sequences exhibited a strong correlation with coronary atherosclerosis burden. Their predicted isomiRs-specific targets were uniquely enriched (compared to their canonical miRNA sequence) in CV Disease (CVD)-related pathways. Two of the isomiRs exhibited discriminative ROC-AUC, and another two showed a correlation with reverse cholesterol transport from cholesterol-loaded macrophages to ApoB-depleted plasma. In summary, we propose a pipeline for exploring circulating isomiR-ome as an approach to uncover novel and strong CVD biomarkers.

Post-COVID-19 Peripartum Cardiomyopathy: Experience from a Large Tertiary Referral Center.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare but potentially devastating complication of pregnancy. Although the pathophysiology of PPCM is not fully understood, there are known risk factors for developing PPCM, which are maternal and gestation related. In the first wave of the coronavirus disease 2019 (COVID-19) pandemic, we witnessed an elevated incidence of PPCM among COVID-19 survivors. OBJECTIVES: To present a single-center case series of three patients diagnosed with peripartum cardiomyopathy after recovered from COVID-19 during the index pregnancy. METHODS: In this single center case study, all patients diagnosed with PPCM at our institute during the examined time frame were included. Electronic medical records were studied. RESULTS: Three patients previously diagnosed with asymptomatic or mildly symptomatic COVID-19 disease during pregnancy presented with PPCM before or shortly after delivery. Patients underwent testing to rule out residual COVID-19 myocarditis, were treated pharmacologically and with wearable defibrillators as needed, and were examined in follow-up 1-9 months after delivery. CONCLUSIONS: Residual endothelial damage due to COVID-19 disease, even if originally mild in presentation, could predispose pregnant patients to PPCM and should be considered as a risk factor when assessing patients with new onset symptoms of heart failure. Further research is needed to confirm this hypothesis and fully determine the underlying pathophysiology. These preliminary findings warrant a high index of suspicion for PPCM in COVID-19 recoverers.

Downstream Imaging Studies Do Not Significantly Improve Outcome in Most Patients with Chest Pain Who Did Not Reach Their Target Heart Rate on a Stress ECHO Study.

Echocardiographic stress tests are often used to evaluate patients who complain of chest pain. However, some patients fail to reach the target heart rate required for the test to be conclusive (usually defined as 85% of the predicted maximal heart rate based on the patient's age) and are often sent for additional imaging tests, such as myocardial perfusion imaging (MPI) or cardiac computed tomography angiography (CTA). Few studies have evaluated the effectiveness of these additional tests in patients who present with chest pain but did not meet the heart rate requirements for a stress test. The primary objective of the study was to evaluate the efficacy of additional imaging tests for patients who experience chest pain during daily activities but are unable to reach the target heart rate currently required for an echocardiographic stress test. The study group included 415 consecutive patients who underwent a stress echocardiogram, did not achieve their target heart rate, and did not demonstrate abnormal changes during the test. The control group consisted of 415 consecutive patients who did reach their target heart rate and demonstrated no signs of ischemia. Demographic and clinical data, medication use, imaging test results (MPI, CTA, and/or coronary catheterization) and documented cardiac events that occurred during 1 year of follow-up were obtained from the electronic medical records. Of the 415 patients in the study group, 73 (17.6%) were referred to another imaging test within 12 months. Of these 73 patients, 59 underwent MPI and 14 underwent cardiac CTA. In 12 of these patients (16.4%) the test was considered to be abnormal, but only 7 patients (1.7%) subsequently underwent a percutaneous intervention (PCI). In the control group, 28 (6.7%) patients were referred for another imaging test. Of these 28 patients, 14 underwent MPI and 14 underwent cardiac CTA. None of these tests were found to be abnormal, but two patients (0.5%) underwent a PCI (p = 0.2 between groups). There were no deaths during the study period and no patients underwent bypass surgery. The majority of the patients who underwent PCI had additional clinical risk factors (diabetes, hypertension, and/or known coronary artery disease), had taken a beta blocker within 24 h prior to the test, and/or did not reach a heart rate above 78% of their target heart rate. Our study suggests that in most patients with chest pain who do not show ischemic changes on a stress echocardiogram, additional imaging studies can be safely deferred, even if the required target heart rate was not reached. However, in patients with diabetes and/or known coronary disease, those who took a beta blocker 24 h prior to the test, or those who did not achieve a heart rate above 78% of the current target heart rate, additional imaging studies should be considered.

The Association of Alanine Aminotransferase Levels With Myocardial Perfusion Imaging and Cardiovascular Morbidity.

INTRODUCTION: Studies suggest that non-alcoholic fatty liver disease (NAFLD) is associated with an independent risk of cardiovascular disease (CVD). We utilized a large cohort of patients undergoing myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) to determine the association between alanine aminotransferase (ALT) as a surrogate marker for presumed NAFLD, and the presence of myocardial ischemia and mortality. METHODS: We retrospectively assessed SPECT-MPI results and medical records of individuals evaluated between 1997 and 2008. We excluded patients with known non-NAFLD liver diseases, ALT values <17 or >340 U/L and absent liver tests. Elevated ALT cases were classified as presumed NAFLD. The primary endpoint was abnormal SPECT-MPI. Secondary endpoints included cardiac death, acute myocardial infarction and all-cause mortality. RESULTS: Of 26,034 patients who underwent SPECT-MPI, 11,324 met inclusion criteria. 1635 (14.4%) patients had elevated ALT. SPECT-MPI results did not differ significantly between subjects with elevated ALT and controls. Elevated ALT was associated with increased risk for the composite endpoint of cardiac death or acute myocardial infarction at 5-year follow-up (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.01-1.67) and in all-cause mortality (HR 1.27, CI 1.02-1.58) but only in patients with normal SPECT-MPI. CONCLUSIONS: The long-term mortality of patients with abnormal SPECT-MPI is not modulated by ALT, likely reflecting an already high risk and established CVD. However, patients with normal SPECT-MPI are at increased risk for a future cardiac event if they have an elevated ALT level, suggesting an important role for NAFLD in earlier stages of CVD.

Diet-induced Fasting Ghrelin Elevation Reflects the Recovery of Insulin Sensitivity and Visceral Adiposity Regression.

CONTEXT: Lower fasting ghrelin levels (FGL) are associated with obesity and metabolic syndrome. OBJECTIVE: We aimed to explore the dynamics of FGL during weight loss and its metabolic and adiposity-related manifestations beyond weight loss. METHODS: This was a secondary analysis of a clinical trial that randomized participants with abdominal obesity/dyslipidemia to 1 of 3 diets: healthy dietary guidelines (HDG), Mediterranean diet (MED), or green-MED diet, all combined with physical activity (PA). Both MED diets were similarly hypocaloric and included 28 g/day walnuts. The green-MED group further consumed green tea (3-4 cups/day) and a Wolffia globosa (Mankai) plant green shake. We measured FGL and quantified body fat depots by magnetic resonance imaging at baseline and after 18 months. RESULTS: Among 294 participants (body mass index = 31.3 kg/m2; FGL = 504 ± 208 pg/mL; retention rate = 89.8%), lower FGL was associated with unfavorable cardiometabolic parameters such as higher visceral adipose tissue (VAT), intrahepatic fat, leptin, and blood pressure (P < 0.05 for all; multivariate models). The ∆FGL18-month differed between men (+7.3 ± 26.6%) and women (-9.2% ± 21.3%; P = 0.001). After 18 months of moderate and similar weight loss among the MED groups, FGL increased by 1.3%, 5.4%, and 10.5% in HDG, MED, and green-MED groups, respectively (P = 0.03 for green-MED vs HDG); sex-stratified analysis revealed similar changes in men only. Among men, FGL18-month elevation was associated with favorable changes in insulin resistance profile and VAT regression, after adjusting for relative weight loss (HbA1c: r = -0.216; homeostatic model of insulin resistance: r = -0.154; HDL-c: r = 0.147; VAT: r = -0.221; P < 0.05 for all). Insulin resistance and VAT remained inversely related with FGL elevation beyond that explained by weight loss (residual regression analyses; P < 0.05). CONCLUSION: Diet-induced FGL elevation may reflect insulin sensitivity recovery and VAT regression beyond weight loss, specifically among men. Green-MED diet is associated with greater FGL elevation.

Loss of left ventricular rotation is a significant determinant of functional mitral regurgitation.

AIM: To evaluate insufficient rotational movement of the left ventricle (LV) as a potential novel mechanism for functional regurgitation of the mitral valve (FMR). METHODS AND RESULTS: We compared reference subjects and patients with LV dysfunction (LVD, ejection fraction EF < 50%) with and without FMR (regurgitant volume RVol>10 ml). Subjects without structural mitral valve pathology undergoing cardiac MRI were evaluated. Delayed enhancement, global LV remodeling parameters, systolic twist and torsion were measured (using manual and novel automated cardiac MRI tissue-tracking). The study included 117 subjects with mean ± SD age 50.4 ± 17.8 years, of which 30.8% were female. Compared to subjects with LVD without FMR (n = 31), those with FMR (n = 37) had similar clinical characteristics, diagnoses, delayed enhancement, EF, and longitudinal strain. Subjects with FMR had significantly larger left ventricles (EDVi:136.6 ± 41.8 vs 97.5 ± 26.2 ml/m, p < 0.0001) with wider separation between papillary muscles (21.1 ± 7.6 vs 17.2 ± 5.7 mm, p = 0.023). Notably, they had lower apical (p < 0.0001) but not basal rotation and lower peak systolic twist (3.1 ± 2.4° vs 5.5 ± 2.5°, p < 0.0001) and torsion (0.56 ± 0.38°/cm vs 0.88 ± 0.52°/cm, p = 0.004). In a multivariate model for RVol including age, gender, twist, LV end-diastolic volume, sphericity index and separation between papillary muscles, only gender, volume and twist were significant. Twist was the most powerful correlate (beta -2.23, CI -3.26 to -1.23 p < 0.001). In patients with FMR, peak systolic twist negatively correlates with RVol (r = -0.73, p < 0.0001). CONCLUSION: Reduced rotational systolic LV motion is significantly and independently associated with RVol among patients with FMR, suggesting a novel pathophysiological mechanism and a potential therapeutic target.

Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial.

OBJECTIVE: To examine the effectiveness of green-Mediterranean (MED) diet, further restricted in red/processed meat, and enriched with green plants and polyphenols on non-alcoholic fatty liver disease (NAFLD), reflected by intrahepatic fat (IHF) loss. DESIGN: For the DIRECT-PLUS 18-month randomized clinical trial, we assigned 294 participants with abdominal obesity/dyslipidaemia into healthy dietary guidelines (HDG), MED and green-MED weight-loss diet groups, all accompanied by physical activity. Both isocaloric MED groups consumed 28 g/day walnuts (+440 mg/day polyphenols provided). The green-MED group further consumed green tea (3-4 cups/day) and Mankai (a Wolffia globosa aquatic plant strain; 100 g/day frozen cubes) green shake (+1240 mg/day total polyphenols provided). IHF% 18-month changes were quantified continuously by proton magnetic resonance spectroscopy (MRS). RESULTS: Participants (age=51 years; 88% men; body mass index=31.3 kg/m2; median IHF%=6.6%; mean=10.2%; 62% with NAFLD) had 89.8% 18-month retention-rate, and 78% had eligible follow-up MRS. Overall, NAFLD prevalence declined to: 54.8% (HDG), 47.9% (MED) and 31.5% (green-MED), p=0.012 between groups. Despite similar moderate weight-loss in both MED groups, green-MED group achieved almost double IHF% loss (-38.9% proportionally), as compared with MED (-19.6% proportionally; p=0.035 weight loss adjusted) and HDG (-12.2% proportionally; p<0.001). After 18 months, both MED groups had significantly higher total plasma polyphenol levels versus HDG, with higher detection of Naringenin and 2-5-dihydroxybenzoic-acid in green-MED. Greater IHF% loss was independently associated with increased Mankai and walnuts intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, changes in microbiome composition (beta-diversity) and specific bacteria (p<0.05 for all). CONCLUSION: The new suggested strategy of green-Mediterranean diet, amplified with green plant-based proteins/polyphenols as Mankai, green tea, and walnuts, and restricted in red/processed meat can double IHF loss than other healthy nutritional strategies and reduce NAFLD in half. TRIAL REGISTRATION NUMBER: NCT03020186.

The effect of green Mediterranean diet on cardiometabolic risk; a randomised controlled trial.

BACKGROUND: A Mediterranean diet is favourable for cardiometabolic risk. OBJECTIVE: To examine the residual effect of a green Mediterranean diet, further enriched with green plant-based foods and lower meat intake, on cardiometabolic risk. METHODS: For the DIRECT-PLUS parallel, randomised clinical trial we assigned individuals with abdominal obesity/dyslipidaemia 1:1:1 into three diet groups: healthy dietary guidance (HDG), Mediterranean and green Mediterranean diet, all combined with physical activity. The Mediterranean diets were equally energy restricted and included 28 g/day walnuts. The green Mediterranean diet further included green tea (3-4 cups/day) and a Wolffia globosa (Mankai strain; 100 g/day frozen cubes) plant-based protein shake, which partially substituted animal protein. We examined the effect of the 6-month dietary induction weight loss phase on cardiometabolic state. RESULTS: Participants (n=294; age 51 years; body mass index 31.3 kg/m2; waist circumference 109.7 cm; 88% men; 10 year Framingham risk score 4.7%) had a 6-month retention rate of 98.3%. Both Mediterranean diets achieved similar weight loss ((green Mediterranean -6.2 kg; Mediterranean -5.4 kg) vs the HDG group -1.5 kg; p<0.001), but the green Mediterranean group had a greater reduction in waist circumference (-8.6 cm) than the Mediterranean (-6.8 cm; p=0.033) and HDG (-4.3 cm; p<0.001) groups. Stratification by gender showed that these differences were significant only among men. Within 6 months the green Mediterranean group achieved greater decrease in low-density lipoprotein cholesterol (LDL-C; green Mediterranean -6.1 mg/dL (-3.7%), -2.3 (-0.8%), HDG -0.2 mg/dL (+1.8%); p=0.012 between extreme groups), diastolic blood pressure (green Mediterranean -7.2 mm Hg, Mediterranean -5.2 mm Hg, HDG -3.4 mm Hg; p=0.005 between extreme groups), and homeostatic model assessment for insulin resistance (green Mediterranean -0.77, Mediterranean -0.46, HDG -0.27; p=0.020 between extreme groups). The LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio decline was greater in the green Mediterranean group (-0.38) than in the Mediterranean (-0.21; p=0.021) and HDG (-0.14; p<0.001) groups. High-sensitivity C-reactive protein reduction was greater in the green Mediterranean group (-0.52 mg/L) than in the Mediterranean (-0.24 mg/L; p=0.023) and HDG (-0.15 mg/L; p=0.044) groups. The green Mediterranean group achieved a better improvement (-3.7% absolute risk reduction) in the 10-year Framingham Risk Score (Mediterranean-2.3%; p=0.073, HDG-1.4%; p<0.001). CONCLUSIONS: The green MED diet, supplemented with walnuts, green tea and Mankai and lower in meat/poultry, may amplify the beneficial cardiometabolic effects of Mediterranean diet. TRIAL REGISTRATION NUMBER: This study is registered under ClinicalTrials.gov Identifier no NCT03020186.

Prevalence of left ventricular hypertrabeculation/noncompaction among patients with congenital dyserythropoietic anemia Type 1 (CDA1).

BACKGROUND: Congenital dyserythropoietic anemia type 1 (CDA1) is a rare autosomal recessive disease characterized by macrocytic anemia, ineffective erythropoiesis, and secondary hemochromatosis. Left-ventricular noncompaction (LVNC) is a cardiomyopathy that is commonly attributed to intrauterine arrest of normal compaction during the endomyocardial morphogenesis. LV hypertrabeculation/noncompaction (LVHT/NC) morphology, however, might exist in various hemoglobinopathies. Our primary objective was to determine whether the pattern of LVHT/NC is more prevalent among patients with CDA1, in comparison to subjects without CDA1, and to find potential risk factors for LVHT/NC among these patients. Our secondary objective was to evaluate the clinical implication of LVHT/NC. METHODS: We retrospectively assessed 32 CDA1 patients (median age 17.5, range 6-61) that underwent routine assessment of iron overload by cardiac magnetic resonance. Number and distribution of noncompacted LV segments were assessed in CDA1 patients and compared to 64 age- and gender-matched patients without CDA1. The ratio of noncompacted to compacted myocardium (NC/C ratio) in end-diastole was calculated for each of the three long-axis views. NC/C ratio > 2.3 was considered diagnostic for LVHT/NC. RESULTS: In multivariate analysis, the presence of CDA1 was independently associated with NC/C ratio > 2.3, a feature of LVHT/NC (adjusted OR = 11.46, 95%CI = 2.6-50.68, p = .001). CDA1 was strongly associated with increased number of myocardial segments exhibiting LVHT/NC pattern. Cardiac volumes and ejection fraction were preserved without clinical adverse events in long term follow-up. CONCLUSIONS: CDA1 patients have a higher prevalence of LVHT/NC than normal individuals, independent of myocardial iron overload and without effect on ejection fraction or clinical outcome.

Comparison of Accuracy of Left Atrial Area and Volume by Two-dimensional Trans-thoracic Echocardiography Versus Computed Tomography.

Left atrial (LA) size is prognostic of cardiovascular events and can be quantified as diameter, area, or volume. While LA area measurement by 2-dimensional (2D) echocardiography is performed by tracing LA borders in the apical 4-chamber view, LA volume is derived from a formula that is based on geometrical assumptions. We compared LA area and volume measurements obtained by trans-thoracic echocardiography (TTE) to those obtained using multi-detector computed tomography (MDCT). Sixty-four patients with MDCT and TTE performed within a 1-week period were included in the study. End-systolic LA area was planimetered from the 4-chamber view by TTE and MDCT. LA end-systolic volume was calculated using the biplane area-length (AL) method in both TTE and MDCT. Mean LA volume measurement using MDCT was significantly larger than TTE measurement (92 ± 31 mL vs 68 ± 27 mL, p <0.001). There was moderate correlation between MDCT and TTE in both LA area (0.74, p <0.0001), and volumetric measurements (0.77, p <0.0001). Bland-Altman agreement plots demonstrated a significantly lower bias and narrower 95% confidence intervals (CI) for the 2D area (bias: -5.5; 95% CI: -14.3 to 3.3) as compared with volumetric measurements (bias: -23.7; 95% CI: -64.9 to 17.5, p <0.0001). Contrary to current guidelines for chamber quantification, 2D TTE LA area has better agreement with MDCT than volumetric measurements by TTE. LA volumetric measurements are desirable; however, they are currently less reliable than the direct LA area tracing by 2D TTE and therefore represent a suboptimal and less reproducible method to determine LA size.

FDG PET/CT of Cardiac Angiosarcoma With Pulmonary Metastases.

We present a case of an adolescent girl with a cardiac mass which was characterized as malignant on FDG PET/CT. In addition, FDG PET/CT revealed multiple hypermetabolic pulmonary lesions. The final diagnosis was primary cardiac angiosarcoma with pulmonary metastases, a rare malignancy especially in female patients at this age group. We emphasize the potential role of FDG PET/CT in patients with a cardiac neoplasm and present a literature review of FDG uptake in benign versus malignant cardiac tumors.

SYNTAX Score Derived From Coronary CT Angiography for Prediction of Complex Percutaneous Coronary Interventions.

RATIONALE AND OBJECTIVES: SYNTAX score is a useful metric determined at the time of invasive coronary angiography (ICA) to assess the complexity of coronary artery disease, and improves prediction of complications at the time of percutaneous complex intervention (PCI). We aimed to determine whether SYNTAX score can be reliably determined from coronary computed tomography angiography (CCTA) and whether a CCTA-derived SYNTAX score can predict complex PCI. MATERIALS AND METHODS: SYNTAX scores were calculated on per-patient, per-vessel, and per-segment basis in 154 consecutive patients who underwent CCTA and ICA. PCI complexity in 113 patients who underwent intervention was defined by total fluoroscopy time and contrast volume. RESULTS: Compared to ICA, CCTA detected 285 of 302 (94%) obstructive lesions in 230 vessels, for which PCI was performed for 154 lesions in 131 vessels. Overall, on a per-patient basis, ICA-derived SYNTAX score was lower in comparison to CCTA-derived score (10.2 ± 8.0 vs 10.9 ± 8.3, P = 0.001). As compared to lesions in the lowest CCTA-derived segmental SYNTAX tertile, lesions in the highest tertile required longer fluoroscopy time (17.5 ± 12 min vs 11.5 ± 7.9 min, P = 0.01) and greater contrast volume (215.4 ± 125.5 mL vs 144.3 ± 49 mL, P = 0.02). CONCLUSION: SYNTAX scores derived from CCTA are concordant with those derived from ICA and correspond with complex PCI.

Diagnostic Accuracy, Image Quality, and Patient Comfort for Coronary CT Angiography Performed Using Iso-Osmolar versus Low-Osmolar Iodinated Contrast: A Prospective International Multicenter Randomized Controlled Trial.

RATIONALE AND OBJECTIVES: The impact of iso-osmolar versus low-osmolar iodinated contrast on diagnostic accuracy for coronary computed tomography angiography (CCTA), against the reference standard of invasive coronary angiography (ICA), has not been determined. We sought to compare in an international multicenter randomized controlled trial the impact of iso-osmolar iodixanol versus low-osmolar iopamidol on diagnostic accuracy, image quality, patient symptoms, and heart rate variability. MATERIALS AND METHODS: Adult patients who were clinically referred for ICA were randomly assigned to receive either iodixanol (n = 133) or iopamidol (n = 133) with an investigational CCTA. CCTA stenosis and image quality were scored by consensus of independent blinded core laboratory readers. Degree of stenosis by ICA was evaluated using quantitative coronary angiography and used to calculate diagnostic accuracy. Heart rate variability and patient-reported symptom questionnaires were compared between the two groups. RESULTS: A total of 266 subjects underwent both CCTA and ICA (57 ± 11 years, 58% male). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for detecting coronary artery disease were 86.8%, 93.7%, 84.6%, 94.7%, and 91.7% for iodixanol and 94.7%, 88.4%, 76.6%, 97.7%, and 90.2% for iopamidol, respectively, on a per-patient level. These values were not significantly different between the two groups. There was no significant difference in image quality and heart rate increase or variability. The majority of patients reported symptoms (59.4%), with no differences in the overall or individual rate of any or moderate to severe symptoms between the two groups. Patients receiving iodixanol reported lower incidence of moderate to severe flushing (3.0% vs. 12.8%, P = .005). Lower rates of moderate to severe symptoms were particularly evident for patients with ≥55 years receiving iodixanol versus iopamidol (8.5% vs. 24.6%, P = .01). CONCLUSIONS: Diagnostic performance and image quality were similar for CCTA performed with iso-osmolar versus low-osmolar iodinated contrast. Indices of patient comfort were improved with iso-osmolar iodinated contrast.

Assessment of aortic stiffness among patients with systemic lupus erythematosus and rheumatoid arthritis by magnetic resonance imaging.

To evaluate aortic stiffness by MRI in female patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) in comparison to controls. We measured aortic strain, distensibility and pulse wave velocity (PWV) by MRI in 30 SLE patients, 31 RA patients and 53 matched controls. Mean PWV in SLE and RA patients were higher in comparison to controls (9.2 ± 4.4 vs. 7.6 ± 3.0 m/s, p = 0.04) and (6.2 ± 2.3 vs. 5.4 ± 1.7, p = 0.04) respectively. Aortic distensibility among RA patients was significantly lower in comparison to controls (4.4 ± 4.6 vs. 5.8 ± 4.9 kPa(-1) × 10(-3), p = 0.04). A significant correlation was found between PWV and age (r = 0.67, p < 0.001), Framingham risk score (r = 0.61, p < 0.001), waist to hip ratio (r = 0.45, p < 0.001), systolic blood pressure (r = 0.37, p = 0.01), diabetes (r = 0.32, p = 0.001) and dyslipidemia (r = 0.32, p = 0.001). In multivariate analysis for the prediction of PWV, variables which were found significant included: RA (p = 0.01), age (p < 0.001) and hypertension (p = 0.01) for patients with RA and SLE (p = 0.02), waist to hip ratio (p < 0.001) and total cholesterol (p < 0.001) for patients with SLE. Arterial stiffness, characterized by metrics of aortic distensibility and pulse wave velocity derived from MRI, is increased in SLE and RA female patients.

Predictors of high-risk coronary artery disease in subjects with normal SPECT myocardial perfusion imaging.

BACKGROUND: While uncommon, normal stress SPECT myocardial perfusion imaging (MPI) can be seen in patients with high-risk coronary artery disease (CAD) by invasive coronary angiography (ICA).The predictors of high-risk CAD in patients with normal SPECT-MPI have not been described. METHODS: We studied 580 patients (age 64 ± 12 years, 49% men) without known CAD who underwent stress-gated SPECT-MPI [exercise (41%) or vasodilator (59%)] <2 months before ICA and had summed stress score (SSS) <4. High-risk CAD was defined as 3 vessels with ≥70% stenosis, 2 vessels with ≥70% stenosis including proximal left anterior descending, or left main with ≥50% stenosis. Obstructive non-high-risk CAD was defined by the presence of a ≥70% stenosis but without having other high-risk criteria. Tenfold cross-validated receiver operating characteristic (ROC) estimates were obtained to assess the predictors of high-risk CAD. RESULTS: Forty-two subjects (7.2%) had high-risk CAD and 168 (29.0%) had obstructive non-high-risk CAD. Variables associated with high-risk CAD were pretest probability of CAD ≥66% (Odds ratio [OR] 3.63, 95% CI 1.6-8.3, P = .002), SSS > 0 (OR 7.46, 95% CI 2.6-21.1, P < 0.001), and abnormal TID (OR 2.16, 95% CI 1.0-4.5, P = 0.044). When substituted for TID, EF change was also predictive of high-risk CAD (OR 0.93, 95% CI 0.9-1.0, P = 0.023). The prevalence of high-risk CAD increased as the number of these predictors increased. In a sub-analysis of patients in whom quantitative total perfusion deficit (TPD) was available, TPD > 0 was also a predictor of high-risk CAD (OR 6.01, 95% CI 1.5-22.2, P = 0.011). CONCLUSION: Several clinical, stress, and SPECT-MPI findings are associated high-risk CAD among patients with normal SPECT-MPI. Consideration of these factors may improve the overall assessment of the likelihood of high-risk CAD in patients undergoing stress SPECT-MPI.

Combined Quantitative Assessment of Myocardial Perfusion and Coronary Artery Calcium Score by Hybrid 82Rb PET/CT Improves Detection of Coronary Artery Disease.

UNLABELLED: Hybrid PET myocardial perfusion imaging (MPI) with CT allows the incorporation of coronary artery calcium (CAC) into the clinical protocol. We aimed to determine whether the combined analysis of MPI and CAC could improve the diagnostic accuracy of PET MPI in detection of obstructive coronary artery disease (CAD). METHODS: Consecutive patients (n = 152; mean age ± SD, 69 ± 12 y) without prior CAD, referred to (82)Rb PET MPI followed by invasive coronary angiography performed within 14 days, were studied. Myocardial perfusion was quantified automatically for left anterior descending, left circumflex, and right coronary artery territories as an ischemic total perfusion deficit (ITPD) for 456 vessels. Global and per-vessel CAC Agatston scores were calculated. Obstructive CAD was defined as 50% or greater stenosis of the left main and 70% or greater stenosis in the left anterior descending, left circumflex, and right coronary arteries. Logistic regression and 10-fold cross validation were used to derive and validate the combined ITPD/logCAC (logarithm of coronary calcium) scores. RESULTS: In the prediction of per-vessel obstructive CAD, the receiver-operating-characteristic area under the curve for combined per-vessel ITPD/logCAC score was higher, 0.85 (95% confidence interval [CI], 0.81-0.89), than standalone ITPD area under the curve, 0.81 (95% CI: 0.76-0.85), and logCAC score, 0.73 (95% CI, 0.68-0.78; P < 0.05). The integrated discrimination improvement of combined per-vessel ITPD/logCAC analysis was 0.07 (95% CI, 0.04-0.09; P < 0.0001), as compared with ITPD alone. CONCLUSION: Combined automatically derived per-vessel ITPD and logCAC score improves accuracy of (82)Rb PET MPI for detection of obstructive CAD.

Prediction of revascularization after myocardial perfusion SPECT by machine learning in a large population.

OBJECTIVE: We aimed to investigate if early revascularization in patients with suspected coronary artery disease can be effectively predicted by integrating clinical data and quantitative image features derived from perfusion SPECT (MPS) by machine learning (ML) approach. METHODS: 713 rest (201)Thallium/stress (99m)Technetium MPS studies with correlating invasive angiography with 372 revascularization events (275 PCI/97 CABG) within 90 days after MPS (91% within 30 days) were considered. Transient ischemic dilation, stress combined supine/prone total perfusion deficit (TPD), supine rest and stress TPD, exercise ejection fraction, and end-systolic volume, along with clinical parameters including patient gender, history of hypertension and diabetes mellitus, ST-depression on baseline ECG, ECG and clinical response during stress, and post-ECG probability by boosted ensemble ML algorithm (LogitBoost) to predict revascularization events. These features were selected using an automated feature selection algorithm from all available clinical and quantitative data (33 parameters). Tenfold cross-validation was utilized to train and test the prediction model. The prediction of revascularization by ML algorithm was compared to standalone measures of perfusion and visual analysis by two experienced readers utilizing all imaging, quantitative, and clinical data. RESULTS: The sensitivity of machine learning (ML) (73.6% ± 4.3%) for prediction of revascularization was similar to one reader (73.9% ± 4.6%) and standalone measures of perfusion (75.5% ± 4.5%). The specificity of ML (74.7% ± 4.2%) was also better than both expert readers (67.2% ± 4.9% and 66.0% ± 5.0%, P < .05), but was similar to ischemic TPD (68.3% ± 4.9%, P < .05). The receiver operator characteristics areas under curve for ML (0.81 ± 0.02) was similar to reader 1 (0.81 ± 0.02) but superior to reader 2 (0.72 ± 0.02, P < .01) and standalone measure of perfusion (0.77 ± 0.02, P < .01). CONCLUSION: ML approach is comparable or better than experienced readers in prediction of the early revascularization after MPS, and is significantly better than standalone measures of perfusion derived from MPS.