Bryan Wai

Increased coronary atherosclerotic plaque vulnerability by coronary computed tomography angiography in HIV-infected men.

Objective:Among HIV-infected patients, high rates of myocardial infarction (MI) and sudden cardiac death have been observed. Exploring potential underlying mechanisms, we used multidetector spiral coronary computed tomography angiography (coronary CTA) to compare atherosclerotic plaque morphology in HIV-infected patients and non-HIV-infected controls. Methods:Coronary atherosclerotic plaques visualized by CTA in HIV-infected (101) and non-HIV-infected (41) men without clinically apparent heart disease matched on cardiovascular risk factors were analyzed for three vulnerability features: low attenuation, positive remodeling, and spotty calcification. Results:Ninety-five percent of HIV-infected patients were receiving ART (median duration 7.9 years) and had well controlled disease (median CD4 cell count, 473 cells/&mgr;l; median HIV RNA <50 copies/ml). Age and traditional cardiovascular risk factors were similar in HIV-infected patients and controls. Among the HIV-infected (versus control) group, there was a higher prevalence of patients with at least one: low attenuation plaque (22.8 versus 7.3%, P = 0.02), positively remodeled plaque (49.5 versus 31.7%, P = 0.05) and high-risk 3-feature plaque (7.9 versus 0%, P = 0.02). Moreover, patients in the HIV-infected (versus control) group demonstrated a higher number of low attenuation plaques (P = 0.01) and positively remodeled plaques (P = 0.03) per patient. Conclusion:Our data demonstrate an increased prevalence of vulnerable plaque features among relatively young HIV-infected patients. Differences in coronary atherosclerotic plaque morphology – namely, increased vulnerable plaque among HIV-infected patients – are here for the first time reported and may contribute to increased rates of MI and sudden cardiac death in this population.

Cardiac Computed Tomography Angiography With Automatic Tube Potential Selection Effects on Radiation Dose and Image Quality

Purpose: Automatic exposure control (AEC) algorithms are widely available in coronary computed tomography angiography (CTA) and have been shown to reduce radiation doses by adjusting tube current to patient size. However, the effects of anthropometry-based automatic potential selection (APS) on image quality and radiation dose are unknown. We sought to investigate the effect of an APS algorithm on coronary CTA radiation dose and image quality. Materials and Methods: For this retrospective case-control study we selected 38 patients who had undergone coronary CTA for coronary artery assessment in whom tube potential and tube current were selected automatically by a combined automatic tube potential and tube current selection algorithm (APS-AEC) and compared them with 38 controls for whom tube voltage was selected according to standard body mass index (BMI) cutoffs and tube current was selected using automatic exposure control (BMI-AEC). Controls were matched for BMI, heart rate, heart rhythm, sex, acquisition mode, and indication for cardiac CTA. Image quality was assessed as contrast-to-noise ratio and signal-to-noise ratio in the proximal coronary arteries. Subjective reader assessment was also made. Total radiation dose (volume-weighted computed tomography dose index) was measured and compared between the 2 groups. In the study group, comparison was made with conventional BMI-guided prior protocols (site protocols and Society of Cardiovascular Computed Tomography recommendations) through disagreement analysis. Results: The APS-AEC cases received 29.8% lower overall radiation dose compared with controls (P=not significant). APS-AEC resulted in a significantly higher signal-to-noise ratio of the proximal coronary arteries (P<0.01) and contrast-to-noise ratio of the left main (P=0.01). In the study cases, the APS resulted in a change in tube potential versus site protocols and Society of Cardiovascular Computed Tomography recommendations in 45% (n=17) and 50% (n=19) of patients, respectively. Conclusion: Automated tube potential selection software resulted in significantly improved objective image quality versus standard BMI-based methods of tube potential selection, without increased radiation doses.

Assessment of mitral valve adaptation with gated cardiac computed tomography: validation with three-dimensional echocardiography and mechanistic insight to functional mitral regurgitation.

Background— Mitral valve (MV) enlargement is a compensatory mechanism capable of preventing functional mitral regurgitation (FMR) in dilated ventricles. Total leaflet area and its relation with closure area measured by 3-dimensional (3D) echocardiography have been related to FMR. Whether these parameters can be assessed with other imaging modalities is not known. Our objectives are to compare cardiac computed tomography (CT)–based measurements of MV leaflets with 3D echocardiography and determine the relationship of these metrics to the presence of FMR. Methods and Results— We used 2 cohorts of patients who had cardiac CT to measure MV total leaflet, closure, and annulus areas. In cohort 1 (26 patients), we validated these CT metrics to 3D echocardiography. In cohort 2 (66 patients), we assessed the relation of MV size with the presence of FMR in 3 populations: heart failure with FMR, heart failure without FMR, and normal controls. Cardiac CT and 3D echocardiography produced similar results for total leaflet (R 2=0.97), closure (R 2=0.89), and annulus areas (R 2=0.84). MV size was the largest in heart failure without FMR compared with controls and patients with FMR (9.1±1.7 versus 7.5±1.0 versus 8.1±0.9 cm2/m2; P<0.01). Patients with FMR had reduced ratios of total leaflet to closure areas and total leaflet to annulus areas when compared with patients without FMR (P<0.01). Conclusions— MV size measured by CT is comparable with 3D echocardiography. MV enlargement in cardiomyopathy suggests leaflet adaptation. Patients with FMR have inadequate adaptation as reflected by decreased ratios of leaflet area and areas determined by ventricle size (annulus and closure areas). These measurements provide additional insight into the mechanism of FMR.

Increased arterial inflammation relates to high-risk coronary plaque morphology in HIV-infected patients.

Background:Mechanisms predisposing HIV-infected patients to increased cardiovascular disease (CVD) risk remain unclear. Objective:To determine the interrelationship between arterial inflammation and high-risk coronary plaque morphology in HIV-infected patients with subclinical coronary atherosclerosis. Methods:Forty-one HIV-infected patients on stable antiretroviral therapy without known CVD but with atherosclerotic plaque on coronary CT angiography were evaluated with 18F-FDG-PET. Patients were stratified into 2 groups based on relative degree of arterial inflammation [aortic target-to-background ratio (TBR)]. High-risk coronary atherosclerotic plaque morphology features were compared between groups. Results:HIV-infected patients with higher and lower TBRs were similar with respect to traditional CVD risk parameters. Among HIV-infected patients with higher TBR, an increased percentage of patients demonstrated at least 1 low-attenuation coronary atherosclerotic plaque (40% vs. 10%, P = 0.02) and at least 1 coronary atherosclerotic plaque with both low attenuation and positive remodeling (35% vs. 10%, P = 0.04). Moreover, in the higher TBR group, both the number of low-attenuation plaques per patient (P = 0.02) and the number of vulnerability features in the most vulnerable plaque (P = 0.02) were increased. TBR grouping remained significantly related to the number of low-attenuation plaques/subject (&bgr; = 0.35, P = 0.004), controlling for age, gender, low-density lipoprotein, duration of HIV, and CD4. Conclusions:These data demonstrate a relationship between arterial inflammation on 18F-FDG-PET and high-risk coronary atherosclerotic plaque features among HIV-infected patients with subclinical coronary atherosclerosis. Further studies are needed to determine whether arterial inflammation and related high-risk coronary morphology increase the risk of clinical CVD events in the HIV population.

Pulmonary Venous Anatomy Imaging with Low-Dose, Prospectively ECG-Triggered, High-Pitch 128-Slice Dual Source Computed Tomography

Background—The efforts to reduce radiation from cardiac computed tomography (CT) are essential. Using a prospectively triggered, high-pitch dual-source CT protocol, we aim to determine the radiation dose and image quality in patients undergoing pulmonary vein (PV) imaging. Methods and Results—In 94 patients (61±9 years; 71% male) who underwent 128-slice dual-source CT (pitch 3.4), radiation dose and image quality were assessed and compared between 69 patients with sinus rhythm and 25 patients with atrial fibrillation. Radiation dose was compared in a subset of 19 patients with prior retrospective or prospectively triggered CT PV scans without high pitch. In a subset of 18 patients with prior magnetic resonance imaging for PV assessment, PV anatomy and scan duration were compared with high-pitch CT. Using the high-pitch protocol, total effective radiation dose was 1.4 (1.3, 1.9) mSv, with no difference between sinus rhythm and atrial fibrillation (1.4 versus 1.5 mSv; P=0.22). No high-pitch CT scans were nondiagnostic or had poor image quality. Radiation dose was reduced with high-pitch (1.6 mSv) compared with standard protocols (19.3 mSv; P<0.0001). This radiation dose reduction was seen with sinus rhythm (1.5 versus 16.7 mSv; P<0.0001) but was more profound with atrial fibrillation (1.9 versus 27.7 mSv; P=0.039). There was excellent agreement of PV anatomy (&kgr; 0.84; P<0.0001) and a shorter CT scan duration (6 minutes) compared with magnetic resonance imaging (41 minutes; P<0.0001). Conclusions—Using a high-pitch dual-source CT protocol, PV imaging can be performed with minimal radiation dose, short scan acquisition, and excellent image quality in patients with sinus rhythm or atrial fibrillation. This protocol highlights the success of new cardiac CT technology to minimize radiation exposure, giving clinicians a new low-dose imaging alternative to assess PV anatomy.

Novel phase-based noise reduction strategy for quantification of left ventricular function and mass assessment by cardiac CT: comparison with cardiac magnetic resonance.

BACKGROUND Tube current modulation in retrospective ECG gated cardiac computed tomography (CT) results in increased image noise and may reduce the accuracy of left ventricular (LV) ejection fraction (EF) and mass assessment. OBJECTIVE To examine the effects of a novel CT phase-based noise reduction (NR) algorithm on LV EF and mass quantification as compared to cardiac magnetic resonance (CMR). METHODS In 40 subjects, we compared the LV EF and mass between CT and CMR. In a subset of 24 subjects with tube current modulated CT, the effect of phase-based noise reduction strategies on contrast-to-noise ratio (CNR) and the assessment of LV EF and mass was compared to CMR. RESULTS There was excellent correlation between CT and CMR for EF (r=0.94) and mass (r=0.97). As compared to CMR, the limits of agreement improved with increasing strength of NR strategy. There was a systematic underestimation of LV mass by CT compared to CMR with no NR (-10.3±10.1g) and low NR (-10.3±12.5g), but was attenuated with high NR (-0.5±8.3g). Studies without NR had lower CNR compared to low and high NR at both the ES phase and ED phase (all p<0.01). CONCLUSIONS A high NR strategy on tube current modulated functional cardiac CT improves correlation of EF compared to CMR and reduces variability of EF and mass evaluation by increasing the CNR. In an effort to reduce radiation dose with tube current modulation, this strategy provides better image quality when LV function and mass quantification is needed.

HDL redox activity is increased in HIV-infected men in association with macrophage activation and non-calcified coronary atherosclerotic plaque.

BACKGROUND HIV is associated with atherosclerosis and low high-density lipoprotein (HDL). With inflammation, HDL becomes dysfunctional. We previously showed that proinflammatory HDL has high HDL redox activity (HRA). In this study, we compare HRA in HIV-infected versus non-HIV-infected subjects and relate HRA to indices of macrophage activation and cardiovascular disease risk. METHODS 102 HIV-infected subjects and 41 matched non-HIV controls without clinical cardiovascular disease underwent coronary CT angiography (CTA) and testing for immune/inflammatory biomarkers. The effect of purified HDL from each study subject on the oxidation rate of dihydrorhodamine-123 (DOR) was normalized to the DOR of pooled HDL from healthy subjects. The normalized ratio DOR subject/DOR pooled was used as a measure of HRA, with higher HRA suggesting dysfunctional HDL. RESULTS HRA was higher in HIV-infected versus non-HIV subjects (1.4 ±0.01 versus 1.3 ±0.01, P=0.03). In multivariate modelling for HRA among all subjects, HIV status remained positively related to HRA (P=0.02), even after controlling for traditional cardiovascular risk factors, comorbid conditions and immune activation. Among HIV-infected subjects, HRA correlated inversely with HDL (rho=-0.32, P=0.002) and log adiponectin (r=-0.28, P=0.006), and correlated positively with log sCD163 (r=0.24, P=0.02) - a monocyte/macrophage activation marker - and with the percentage of non-calcified coronary atherosclerotic plaque (r=0.29, P=0.03). sCD163 remained significantly associated with HRA in multivariate modelling among HIV-infected subjects (P=0.03). CONCLUSIONS These data demonstrate increased HRA among HIV-infected subjects versus matched non-HIV subjects with comparable HDL levels. In HIV-infected subjects, HRA relates to macrophage activation and to non-calcified coronary atherosclerotic plaque, which may be rupture-prone. Further studies are needed in HIV-infected patients to elucidate the interplay between immune activation, HDL function and CVD risk. CLINICAL TRIAL REGISTRATION NUMBER NCT 00455793.

Preprocedural Imaging for Patients with Atrial Fibrillation and Heart Failure

Various electrophysiological procedures and device implantation has been shown to improve morbidity and mortality in patients with atrial fibrillation (AF) and patients with heart failure (HF). Noninvasive cardiac imaging is used extensively in the preprocedural patient selection and for procedural guidance. In this review, we will discuss the application of preprocedural cardiac imaging in patients with AF prior to pulmonary vein and left atrial ablation as well as insertion of left atrial occluder device. We also discuss the role of noninvasive cardiac imaging in the selection of appropriate HF patients for device therapy as well as their use in guiding implantation of biventricular pacemaker for cardiac resynchronization therapy by assessing left ventricular ejection fraction, coronary venous anatomy, mechanical dyssynchrony and myocardial scar. We describe new research associated with preprocedural imaging in these patient cohorts.

Incremental value of cystatin C over conventional renal metrics for predicting clinical response and outcomes in cardiac resynchronization therapy: The BIOCRT study.

BACKGROUND Despite the benefit of CRT in select patients with heart failure (HF), there remains significant need for predicting those at risk for adverse outcomes for this effective but costly therapy. CysC, an emerging marker of renal function, is predictive of worsening symptoms and mortality in patients with HF. This study assessed the utility of baseline and serial measures of cystatin C (CysC), compared to conventional creatinine-based measures of renal function (estimated glomerular filtration rate, eGFR), in predicting clinical outcomes following cardiac resynchronization therapy (CRT). METHODS In 133 patients, we measured peripheral venous (PV) and coronary sinus (CS) CysC concentrations and peripheral creatinine levels at the time of CRT implant. Study endpoints included clinical response to CRT at 6 months and major adverse cardiac events (MACE) at 2 years. RESULTS While all 3 renal metrics were predictive of MACE (all adjusted p ≤ 0.02), only CysC was associated with CRT non-response at 6 months (adjusted odds ratio 3.6, p = 0.02). CysC improved prediction of CRT non-response (p ≤ 0.003) in net reclassification index analysis compared to models utilizing standard renal metrics. Serial CysC > 1mg/L was associated with 6-month CRT non-response and reduced 6-minute walk distance as well as 2-year MACE (all p ≤ 0.04). CONCLUSION In patients undergoing CRT, CysC demonstrated incremental benefit in the prediction of CRT non-response when compared to standard metrics of renal function. Baseline and serial measures of elevated CysC were predictive of CRT non-response and functional status at 6 months as well as long-term clinical outcomes.

Utility of dual-source computed tomography in cardiac resynchronization therapy—DIRECT study

BACKGROUND Dual-source computed tomography (CT) can evaluate left ventricular (LV) dyssynchrony, myocardial scar, and coronary venous anatomy in patients undergoing cardiac resynchronization therapy (CRT). OBJECTIVE We aimed to determine whether dual-source CT predicts clinical CRT outcomes and reduces intraprocedural time. METHODS In this prospective study, 54 patients scheduled for CRT (mean age 63 ± 11 years; 74% men) underwent preprocedural CT to assess their venous anatomy as well as CT-derived dyssynchrony metrics and myocardial scar. Based on 1:1 randomization, the implanting physician had preimplant knowledge of the venous anatomy in half the patients. In blinded analyses, we measured time to maximal wall thickness and inward wall motion to determine (1) CT global and segmental dyssynchrony and (2) concordance of lead location to regional LV mechanical contraction. End points were 6-month CRT response measured using heart failure clinical composite score and 2-year major adverse cardiac events (MACE). RESULTS There were 72% CRT responders and 17% with MACE. Two wall motion dyssynchrony indices-global wall motion and opposing anteroseptal-inferolateral wall motion-predicted MACE (P < .01). Lead location concordant to regions of maximal wall thickness was associated with less MACE (P < .01). No CT dyssynchrony metrics predicted 6-month CRT response (P = NS for all). Myocardial scar (43%), posterolateral wall scar (28%), and total scar burden did not predict outcomes (P = NS for all). Preknowledge of coronary venous anatomy by CT did not reduce implant or fluoroscopy time (P = NS for both). CONCLUSION Two CT dyssynchrony metrics predicted 2-year MACE, and LV lead location concordant to regions of maximal wall thickness was associated with less MACE. Other CT factors had little utility in CRT.