Jatin R. Matta

Hypercortisolism Is Associated With Increased Coronary Arterial Atherosclerosis: Analysis of Noninvasive Coronary Angiography Using Multidetector Computerized Tomography

BACKGROUND Observational studies show that glucocorticoid therapy and the endogenous hypercortisolism of Cushings syndrome (CS) are associated with increased rates of cardiovascular morbidity and mortality. However, the causes of these findings remain largely unknown. OBJECTIVE To determine whether CS patients have increased coronary atherosclerosis. DESIGN A prospective case-control study was performed. SETTING Subjects were evaulated in a clinical research center. SUBJECTS Fifteen consecutive patients with ACTH-dependent CS, 14 due to an ectopic source and 1 due to pituitary Cushings disease were recruited. Eleven patients were studied when hypercortisolemic; 4 patients were eucortisolemic due to medication (3) or cyclic hypercortisolism (1). Fifteen control subjects with at least one risk factor for cardiac disease were matched 1:1 for age, sex, and body mass index. PRIMARY OUTCOME VARIABLES Agatston score a measure of calcified plaque and non-calcified coronary plaque volume were quantified using a multidetector CT (MDCT) coronary angiogram scan. Additional variables included fasting lipids, blood pressure, history of hypertension or diabetes, and 24-hour urine free cortisol excretion. RESULTS CS patients had significantly greater noncalcified plaque volume and Agatston score (noncalcified plaque volume [mm(3)] median [interquartile ranges]: CS 49.5 [31.4, 102.5], controls 17.9 [2.6, 25.3], P < .001; Agatston score: CS 70.6 [0, 253.1], controls 0 [0, 7.6]; P < .05). CS patients had higher systolic and diastolic blood pressures than controls (systolic: CS 143 mm Hg [135, 173]; controls, 134 [123, 136], P < .02; diastolic CS: 86 [80, 99], controls, 76 [72, 84], P < .05). CONCLUSIONS Increased coronary calcifications and noncalcified coronary plaque volumes are present in patients with active or previous hypercortisolism. Increased atherosclerosis may contribute to the increased rates of cardiovascular morbidity and mortality in patients with glucocorticoid excess.

Increased Coronary Vessel Wall Thickness in HIV-Infected Young Adults

BACKGROUND Individuals with long-term human immunodeficiency virus (HIV) infection are at risk for premature vasculopathy and cardiovascular disease (CVD). We evaluated coronary vessel wall thickening, coronary plaque, and epicardial fat in patients infected with HIV early in life compared with healthy controls. METHODS This is a prospective cross-sectional study of 35 young adults who acquired HIV in early life and 11 healthy controls, free of CVD. Time resolved phase-sensitive dual inversion recovery black-blood vessel wall magnetic resonance imaging (TRAPD) was used to measure proximal right coronary artery (RCA) wall thickness, and multidetector computed tomography (CT) angiography was used to quantify coronary plaque and epicardial fat. RESULTS RCA vessel wall thickness was significantly increased in HIV-infected patients compared with sex- and race-matched controls (1.32 ± 0.21 mm vs 1.09 ± 0.14 mm, P = .002). No subject had discrete plaque on CT sufficient to cause luminal narrowing, and plaque was not related to RCA wall thickness. In multivariate regression analyses, smoking pack-years (P = .004) and HIV infection (P = .007) were independently associated with thicker RCA vessel walls. Epicardial fat did not differ between groups. Among the HIV-infected group, duration of antiretroviral therapy (ART) (P = .02), duration of stavudine exposure (P < .01), low-density lipoprotein cholesterol (P = .04), and smoking pack-years (P < .01) were positively correlated with RCA wall thickness. CONCLUSIONS This investigation provides evidence of subclinical coronary vascular disease among individuals infected with HIV in early life. Increased duration of ART, hyperlipidemia, and smoking contributed to proximal RCA thickening, independent of atherosclerotic plaque quantified by CT. These modifiable risk factors appear to influence early atherogenesis as measured by coronary wall thickness and may be important targets for CVD risk reduction.

Non-calcified coronary plaque volume inversely related to CD4(+) T-cell count in HIV infection.

BACKGROUND Non-calcified coronary artery plaque (NCAP) might be an important predictor of cardiovascular events; however, few studies have directly measured NCAP in HIV-infected individuals. METHODS We completed a prospective cross-sectional evaluation of NCAP and coronary calcium scores using computed tomography angiography in HIV-infected patients (n=26) without known coronary artery disease (CAD), but who had one or more CAD risk factor(s), and compared them with controls matched on age, race, sex, body mass index and Framingham Risk Score (n=26). RESULTS There was no difference in coronary calcium scores (114 ± 218 versus 124 ± 298; P=0.89) or NCAP volume (65 ± 86 mm(3) versus 63 ± 82 mm(3); P=0.38) between HIV-infected patients and controls, respectively. Among HIV-infected patients, lower CD4(+) T-cell count was associated with increased NCAP volume (r=-0.52, P=0.006). The CD4(+) T-cell count remained a significant predictor of NCAP in a multivariate analysis that adjusted for age and duration of antiretroviral therapy. CONCLUSIONS Plaque burden is similar between HIV-infected and uninfected individuals when matched on traditional CAD risk factors; however, immune function might mediate the development of atherosclerosis in HIV infection.

Free-breathing Single Navigator Gated Cine Cardiac Magnetic Resonance at 3 T: Feasibility Study in Patients

Background: Cardiac magnetic resonance imaging (CMRI) is an important tool to assess cardiac function. However, one of the limitations of CMRI is the need for frequent breath-holding (BH) steps. This may be inconvenient to some patients and limit the use of this modality in patients unable to cooperate because of cognitive reasons or physically incapable of performing the required BH steps. The purpose of this study is to overcome the intrinsic timing and computation limitations of dual-navigator cine imaging and demonstrate the feasibility of free-breathing (FB) cine cardiac left ventricular function with a single-respiratory-navigator gating at 3 T. Results: Eight participants underwent cine CMRI with both the conventional 2-dimensional cine BH and FB navigator-gated techniques. Scan parameters were identical, except in the FB technique, in which a respiratory navigator and only 2 signal averages were used. Images were scored for quality. Left ventricular end-systolic volume and end-diastolic volume were calculated. The differences in the end-systolic volume and end-diastolic volume assessed by the BH and FB were not statistically significant with P = 0.9 and 0.2, respectively. There was a good agreement between LV volumes with the limits of agreement (±2 SD = ±22.36 mL). Image quality score was not significantly different (P = 0.76). Conclusions: Free-breathing cine imaging utilizing a single-respiratory-navigator gating technique is comparable to conventional BH technique in both qualitative and quantitative imaging measures. Therefore, the FB cine technique can be used as an alternative for children and patients who are unable to hold their breath.

X chromosome parental origin and aortic stiffness in turner syndrome

Aortic abnormalities contribute to increased morbidity and mortality of women with Turner syndrome (TS). Impaired aortic stiffness may prove to have clinical prognostic value in TS as is the case in other diseases such as Marfan syndrome, diabetes and hypertension. Additionally, the parental origin of the X chromosome in TS may influence aortic stiffness.

Feasibility of Coronary Artery Wall Thickening Assessment in Asymptomatic Coronary Artery Disease using Phase-Sensitive Dual Inversion Recovery MRI at 3T

OBJECTIVES The purpose of this study was to (a) investigate the image quality of phase-sensitive dual-inversion recovery (PS-DIR) coronary wall imaging in healthy subjects and in subjects with known coronary artery disease (CAD) and to (b) investigate the utilization of PS-DIR at 3T in the assessment of coronary artery thickening in subjects with asymptomatic but variable degrees of CAD. MATERIALS AND METHODS A total of 37 subjects participated in this institutional review board-approved and HIPAA-compliant study. These included 21 subjects with known CAD as identified on multidetector computed tomography angiography (MDCT). Sixteen healthy subjects without known history of CAD were included. All subjects were scanned using free-breathing PS-DIR magnetic resonance imaging (MRI) for the assessment of coronary wall thickness at 3T. Lumen-tissue contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR) and quantitative vessel parameters including lumen area and wall thickness were measured. Statistical analyses were performed. RESULTS PS-DIR was successfully completed in 76% of patients and in 88% of the healthy subjects. Phase-sensitive signed-magnitude reconstruction, compared to modulus-magnitude images, significantly improved lumen-tissue CNR in healthy subjects (26.73±11.95 vs. 14.65±9.57, P<.001) and in patients (21.45±7.61 vs. 16.65±5.85, P<.001). There was no difference in image CNR and SNR between groups. In arterial segments free of plaques, coronary wall was thicker in patients in comparison to healthy subjects (1.74±0.27 mm vs. 1.17±0.14 mm, P<.001), without a change in lumen area (4.51±2.42 mm2 vs. 5.71±3.11mm2, P=.25). CONCLUSIONS This is the first study to demonstrate the feasibility of successfully obtaining vessel wall images at 3T using PS-DIR in asymptomatic patients with known variable degrees of CAD as detected by MDCT. This was achieved with a fixed subject-invariant planning of blood signal nulling. With that limitation alleviated, PS-DIR coronary wall MRI is capable of detecting arterial thickening and positive arterial remodeling at 3T in asymptomatic CAD.

Aneurysmal dilatation of medium caliber arteries in Turner syndrome.

Turner syndrome is the most common chromosomal abnormality in female subjects, affecting 1 in 2000 live births. The condition is associated with a generalized vasculopathy as well as congenital cardiac and other defects. We report aneurysmal dilation of medium caliber arteries involving the celiac axis and coronary vessels in two women with Turner syndrome.

Coronary calcification in adults with Turner syndrome

PurposeAdults with Turner syndrome (TS) have an increased predisposition to ischemic heart disease. The quantitative relationship between coronary atherosclerosis and TS has yet to be established.MethodsA total of 128 females (62 with TS) participated in this prospective study. Coronary computed tomography angiography was performed to measure coronary calcified plaque burden, and prevalent noncalcified plaque burden. Regression analysis was used to study the effects of TS and traditional cardiovascular disease risk factors on coronary plaque burden.ResultsAdults with TS were 63% more likely to have coronary calcifications than controls (odds ratio 1.63, 95% confidence interval: 1.02, 2.61, P = 0.04), with an age cutoff of 51.7 years for a probability of >50% for the presence of coronary calcifications, when compared to 55.7 years in female controls. The average age of TS patients with calcified plaques was significantly lower than that of controls with calcified plaques (51.5 ± 8.9 years vs. 60.5 ± 7.0 years, P < 0.001). Age increased the likelihood of coronary calcifications by 13% per year (odds ratio 1.13, confidence interval 95%: 1.07–1.19, P < 0.001).ConclusionThis study demonstrates a higher prevalence and earlier onset of calcified coronary plaques in TS. These findings have important implications for cardiovascular risk assessment and the management of patients with TS.

Personalized Statin Therapy and Coronary Atherosclerotic Plaque Burden in Asymptomatic Low/Intermediate-Risk Individuals

Background: Current guidelines for the primary prevention of atherosclerotic cardiovascular disease are based on the estimation of a predicted 10-year cardiovascular disease risk and the average relative risk reduction estimates from statin trials. In the clinical setting, however, decision-making is better informed by the expected benefit for the individual patient, which is typically lacking. Consequently, a personalized statin benefit approach based on absolute risk reduction over 10 years (ARR10 benefit threshold ≥2.3%) has been proposed as a novel approach. However, how this benefit threshold relates with coronary plaque burden in asymptomatic individuals with low/intermediate cardiovascular disease risk is unknown. Aims: In this study, we compared the predicted ARR10 obtained in each individual with plaque burden detected by coronary computed tomography angiography. Methods and Results: Plaque burden (segment volume score, segment stenosis score, and segment involvement score) was assessed in prospectively recruited asymptomatic subjects (n = 70; 52% male; median age 56 years [interquartile range 51–64 years]) with low/intermediate Framingham risk score (< 20%). The expected ARR10 with statin in the entire cohort was 2.7% (1.5–4.6%) with a corresponding number needed to treat over 10 years of 36 (22–63). In subjects with an ARR10 benefit threshold ≥2.3% (vs. < 2.3%), plaque burden was significantly higher (p = 0.02). Conclusion: These findings suggest that individuals with higher coronary plaque burden are more likely to get greater benefit from statin therapy even among asymptomatic individuals with low cardiovascular risk.