Associations of ABCG1-mediated cholesterol efflux capacity with coronary artery lipid content assessed by near-infrared spectroscopy.

BACKGROUND: Although high-density lipoprotein (HDL) has atheroprotective properties, the association of HDL functionality with coronary plaques remains unclear. METHODS: We investigated the association between HDL-mediated cholesterol efflux capacity (CEC) and coronary lipid burden in 74 patients who underwent near-infrared spectroscopy (NIRS) imaging for acute coronary syndrome (ACS) or stable ischemic symptoms. We measured baseline HDL-mediated CEC, distinguishing the specific pathways, and stratified patients according to their median CEC values. Coronary lipid burden was assessed as lipid core burden index (LCBI) using NIRS at baseline (n=74) and on serial imaging (n=47). RESULTS: Patients with baseline ATP-binding cassette transporter G1 (ABCG1)-mediated CEC > median had a greater baseline LCBI {74 [20, 128] vs. 32 [5, 66]; P=0.04} or change in LCBI {-30 [-89, 0] vs. -3 [-16, 0]; P=0.048}. In addition to a negative association between baseline LCBI and change in LCBI (standardized ß=-0.31; P=0.02), multivariable analysis demonstrated a significant interaction effect between clinical presentation of coronary artery disease (CAD) and baseline ABCG1-mediated CEC on change in LCBI (P=0.003), indicating that baseline ABCG1-mediated CEC was inversely associated with change in LCBI in patients with ACS (standardized ß=-0.79, P=0.003), but not in those with stable ischemic symptoms (P=0.52). CONCLUSIONS: In this study, ABCG1-mediated CEC, but not ATP-binding cassette transporter A1 and scavenger receptor B type I, was associated with regression of coronary artery lipid content, especially in patients with high-risk phenotype. Further studies are required to determine the roles of ABCG1 pathway in the development coronary plaques.

Aortic distensibility is associated with both resting and hyperemic coronary blood flow.

A large body of evidence demonstrates an independent association between arterial stiffness and prospective risk of cardiovascular events. A reduction in coronary perfusion is presumed to underscore this association; however, studies confirming this are lacking. This study compared invasive measures of coronary blood flow (CBF) with cardiac magnetic resonance (CMR)-derived aortic distensibility (AD). Following coronary angiography, a Doppler FloWire and infusion microcatheter were advanced into the study vessel. Average peak velocity (APV) was acquired at baseline and following intracoronary adenosine to derive coronary flow velocity reserve (CFVR = hyperemic APV/resting APV) and CBF [π × (diameter)2 × APV × 0.125]. Following angiography, patients underwent CMR to evaluate distensibility at the ascending aorta (AA), proximal descending aorta (PDA) and distal descending aorta (DDA). Fifteen participants (53 ± 13 yr) with minor epicardial disease (maximum stenosis <30%) were enrolled. Resting CBF was 44.1 ± 11.9 mL/min, hyperemic CBF was 143.8 ± 37.4 mL/min, and CFVR was 3.15 ± 0.48. AD was 3.89 ± 1.72·10-3mmHg-1 at the AA, 4.08 ± 1.80·10-3mmHg-1 at the PDA, and 4.42 ± 1.67·10-3mmHg-1 at the DDA. All levels of distensibility correlated with resting CBF (R2 = 0.350-0.373, P < 0.05), hyperemic CBF (R2 = 0.453-0.464, P < 0.01), and CFVR (R2 = 0.442-0.511, P < 0.01). This study demonstrates that hyperemic and, to a lesser extent resting CBF, are significantly associated with measures of aortic stiffness in patients with only minor angiographic disease. These findings provide further in vivo support for the observed prognostic capacity of large artery function in cardiovascular event prediction.NEW & NOTEWORTHY Cardiac magnetic resonance-derived aortic distensibility is associated with invasive measures of coronary blood flow. Large artery function is more strongly correlated with hyperemic than resting blood flow. Increased stiffness may represent a potential target for novel antianginal medications.

Serial changes in vessel walls of renal arteries after catheter-based renal artery denervation: insights from volumetric computed tomography analysis.

AIM: Radiofrequency ablation of peri-arterial renal autonomic nerves has been studied as a potential therapeutic option for resistant hypertension. While recent clinical trials have reported its efficacy, there is paucity of data addressing the effects of the procedure on renal arteries, such as changes in vessel and lumen areas. Herein, the effect of atheroma burden on renal arteries after renal denervation was assessed using computed tomography (CT) imaging. MATERIALS AND METHODS: Serial renal artery CT imaging was conducted in 38 patients from the EnligHTN™ I study, a prospective, multicenter study evaluating the efficacy of the EnligHTN multi-electrode radiofrequency ablation catheter in resistant hypertensive subjects. Cross-sectional images of renal arteries at 1 mm intervals were acquired using commercially available software (3mensio Structural Heart version 5.1). Vessel and lumen areas were manually traced in each image. Vessel wall volume (VWV) and percent vessel wall volume (P-VWV) were calculated. The measurements within the ablation (first 30 mm segments) and the non-ablation (subsequent 30 mm segment after the first bifurcation of renal arteries) zones were compared. RESULTS: On serial evaluation, greater increase in P-VWV and VWV was observed in the ablation zone (change in P-VWV, 6.7%±5.1% vs 3.6%±2.8%, P=0.001; change in VWV, 106.3±87.4 vs 23.0±18.2 mm3, P=0.001). Receiver-operating characteristic analysis demonstrated baseline P-VWV in the ablation zone >37.1% as an optimal cutoff value to predict its substantial progression after the procedure (area under the curve=0.88, sensitivity 89.8%, specificity 79.1%). CONCLUSION: Change in vessel wall was greater within the segments receiving renal artery denervation. Baseline VWV predicted its substantial increase after the procedure. These observations suggest that atheroma burden within the renal arteries is a potential contributing factor to vascular changes after renal sympathetic denervation.

The relationship between segmental wall shear stress and lipid core plaque derived from near-infrared spectroscopy.

BACKGROUND AND AIMS: Wall shear stress (WSS) has an important role in the natural history of coronary atherosclerosis. The aim of this study is to investigate the relationship between WSS and the lipid content of atherosclerotic plaques as assessed by near-infrared spectroscopy (NIRS). METHODS: We performed serial NIRS and intravascular ultrasound (IVUS) upon Doppler coronary flow guidewire of coronary plaques at baseline and after 12-18 months in 28 patients with <30% angiographic stenosis, who presented with coronary artery disease. Segmental WSS, plaque burden and NIRS-derived lipid rich plaque (LRP) were evaluated at both time-points in 482 consecutive 2-mm coronary segments. RESULTS: Segments with LRP at baseline (n = 106) had a higher average WSS (1.4 ±â€¯0.6 N/m2), compared to those without LRP (n = 376) (1.2 ±â€¯0.6 N/m2, p<0.001). In segments without baseline LRP, WSS was higher in those who subsequently developed new LRP (n = 35) than those who did not (n = 341) (1.4 ±â€¯0.8 vs. 1.1 ±â€¯0.6 N/m2, p=0.002). Conversely, in segments with baseline LRP, WSS was lower in those who had regression of lipid content (n = 41) than those who did not (n = 65) (1.2 ±â€¯0.4 vs. 1.6 ±â€¯0.7 N/m2, p=0.007). Segments with the highest tertile of WSS displayed greater progression of LCBI irrespective of baseline lipid content (p<0.001). Multivariate analysis revealed that baseline WSS (p=0.017), PAV (p<0.001) and LCBI (p<0.001) were all independent predictors of change in LCBI over time. CONCLUSIONS: Coronary segments with high WSS associate with progression of lipid content over time, which may indicate transformation to a more vulnerable phenotype.

Evaluation of human coronary vasodilator function predicts future coronary atheroma progression.

OBJECTIVE: Coronary vasodilator function and atherosclerotic plaque progression have both been shown to be associated with adverse cardiovascular events. However, the relationship between these factors and the lipid burden of coronary plaque remains unknown. These experiments focus on investigating the relationship between impaired coronary vasodilator function (endothelium dependent (salbutamol) and endothelium independent (glyceryl trinitrate)) and the natural history of atheroma plaque progression and lipid burden using dual modality intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) imaging. METHODS: 33 patients with stable chest pain or acute coronary syndrome underwent serial assessment of coronary vasodilator function and intracoronary plaque IVUS and NIRS imaging. Coronary segmental macrovascular response (% change segmental lumen volume (ΔSLV)), plaque burden (per cent atheroma volume (PAV)), lipid core (lipid-rich plaque (LRP) and lipid core burden index (LCBI)) were measured at baseline and after an interval of 12-18 months (n=520 segments). RESULTS: Lipid-negative coronary segments which develop into LRP over the study time period demonstrated impaired endothelial-dependent function (-0.24±2.96 vs 5.60±1.47%, P=0.04) and endothelial-independent function (13.91±4.45 vs 21.19±3.19%, P=0.036), at baseline. By multivariate analysis, endothelial-dependent function predicted ∆LCBI (ß coefficient: -3.03, 95% CI (-5.81 to -0.25), P=0.033) whereas endothelial-independent function predicted ∆PAV (ß coefficient: 0.07, 95% CI (0.04 to 0.10), P<0.0001). CONCLUSIONS: Epicardial coronary vasodilator function is a determinant of future atheroma progression and composition irrespective of the nature of clinical presentation. TRIAL REGISTRATION NUMBER: ACTRN12612000594820, Post-results.

Renal sympathetic denervation increases renal blood volume per cardiac cycle: a serial magnetic resonance imaging study in resistant hypertension.

AIM: Preclinical studies have demonstrated improvements in renal blood flow after renal sympathetic denervation (RSDN); however, such effects are yet to be confirmed in patients with resistant hypertension. Herein, we assessed the effects of RSDN on renal artery blood flow and diameter at multiple time points post-RSDN. METHODS AND RESULTS: Patients (n=11) with systolic blood pressures ≥160 mmHg despite taking three or more antihypertensive medications at maximum tolerated dose were recruited into this single-center, prospective, non-blinded study. Magnetic resonance imaging indices included renal blood flow and renal artery diameters at baseline, 1 month and 6 months. In addition to significant decreases in blood pressures (p<0.0001), total volume of blood flow per cardiac cycle increased by 20% from 6.9±2 mL at baseline to 8.4±2 mL (p=0.003) at 1 month and to 8.0±2 mL (p=0.04) 6 months post-procedure, with no changes in the renal blood flow. There was a significant decrease in renal artery diameters from 7±2 mm at baseline to 6±1 mm (p=0.03) at 1 month post-procedure. This decrease was associated with increases in maximum velocity of blood flow from 73±20 cm/s at baseline to 78±19 cm/s at 1 month post-procedure. Notably, both parameters reverted to 7±2 mm and 72±18 cm/s, respectively, 6 months after procedure. CONCLUSION: RSDN improves renal physiology as evidenced by significant improvements in total volume of blood flow per cardiac cycle. Additionally, for the first time, we identified a transient decrease in renal artery diameters immediately after procedure potentially caused by edema and inflammation that reverted to baseline values 6 months post-procedure.

High-density lipoprotein cholesterol associated with change in coronary plaque lipid burden assessed by near infrared spectroscopy.

BACKGROUND AND AIMS: Little is known about the relation between serum lipid parameters and serial change in plaque composition using in vivo coronary imaging. The aim of this study was to examine the association between serum lipids and change in coronary plaque lipid burden assessed by near-infrared spectroscopy (NIRS). METHODS: We performed serial NIRS-intravascular ultrasound studies in 49 patients who underwent coronary angiography for an acute coronary syndrome (ACS) or stable ischemic symptoms. Univariable and multivariable linear regression analyses were applied to evaluate the relationship between serum lipid parameters and change in lipid core burden index at the 4-mm maximal segment (max LCBI4mm). RESULTS: Mean patient age was 61 ± 9 y, 29% were women, 35% had an ACS clinical presentation, 78% received statin therapy at baseline, and median low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), total cholesterol and triglyceride levels were 101, 43, 174 and 133 mg/dL, respectively. During a median follow-up period of 13 months, max LCBI4mm significantly decreased from 277 to 194 (p = 0.001). On univariable analysis, the percent change in HDL-C negatively associated with the change in max LCBI4mm (ß = -3.19, p = 0.004). There were no significant associations between the other lipid parameters and change in max LCBI4mm. On multivariable analysis, percent change in HDL-C remained significantly associated with the change in max LCBI4mm (p = 0.002). CONCLUSIONS: Change in HDL-C, but not other lipids parameters, associated with changes in coronary plaque lipid burden assessed by NIRS. These findings highlight the potential therapeutic importance of high-density lipoprotein on serial change in plaque composition.

The predictive capabilities of a novel cardiovascular magnetic resonance derived marker of cardiopulmonary reserve on established prognostic surrogate markers in patients with pulmonary vascular disease: results of a longitudinal pilot study.

BACKGROUND: No unified method exists to effectively predict and monitor progression of pulmonary arterial hypertension (PAH). We assessed the longitudinal relationship between a novel marker of cardiopulmonary reserve and established prognostic surrogate markers in patients with pulmonary vascular disease. METHODS AND RESULTS: Twenty participants with confirmed (n = 14) or at high risk (n = 6) for PAH underwent cardiovascular magnetic resonance (CMR) at baseline and after ~6 months of guideline-appropriate management. Ten PAH participants underwent RHC within 48 h of each CMR. RHC (mean pulmonary arterial pressure, mPAP; pulmonary vascular resistance index, PVRI; cardiac index, CI) and phase-contrast CMR (mean pulmonary arterial blood flow velocity, meanPAvel) measurements were taken at rest and during continuous adenosine infusion (70/140/210 mcg/kg/min). Initial meanPAvel's (rest and hyperemic) were correlated with validated surrogate prognostic parameters (CMR: RV ejection fraction, RVEF; RV end systolic volume indexed, RVESVI; RHC: PVRI, CI; biomarker: NT-pro brain natriuretic peptide, NTpBNP; clinical: 6-min walk distance, 6MWD), a measure of pulmonary arterial stiffness (elastic modulus) and volumetric estimation of RV ventriculoarterial (VA) coupling. Changes in meanPAvel's were correlated with changes in comparator parameters over time. At initial assessment, meanPAvel at rest correlated significantly with PVRI (inversely), CI (positively) and elastic modulus (inversely) (R 2 > 0.37,P < 0.05 for all), whereas meanPAvel at peak hyperemia correlated significantly with PVRI, RVEF, RVESVI, 6MWD, elastic modulus and VA coupling (R 2 > 0.30,P < 0.05 for all). Neither resting or hyperemia-derived meanPAvel correlated with NTpBNP levels. Initial meanPAvel at rest correlated significantly with RVEF, RVESVI, CI and VA coupling at follow up assessment (R 2 > 0.2,P < 0.05 for all) and initial meanPAvel at peak hyperemia correlated with RVEF, RVESVI, PVRI and VA coupling (R 2 > 0.37,P < 0.05 for all). Change in meanPAvel at rest over time did not show statistically significant correlation with change in prognostic parameters, while change in meanPAvel at peak hyperemia did show a significant relationship with ΔRVEF, ΔRVESVI, ΔNTpBNP and ΔCI (R 2 > 0.24,P < 0.05 for all). CONCLUSION: MeanPAvel during peak hyperemia correlated with invasive, non-invasive and clinical prognostic parameters at different time points. Further studies with predefined clinical endpoints are required to evaluated if this novel tool is a marker of disease progression in patients with pulmonary vascular disease.

Intravenous Recombinant Tissue Plasminogen Activator Therapy for Acute Basilar Artery Ischemic Stroke Following Transfemoral Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve implantation (TAVI) can now be considered a standard of care for inoperable and high-risk surgical patients with severe aortic stenosis, and its uptake worldwide is rapidly increasing. Indeed, many centers performing the procedure have now moved towards treating intermediate-risk patients with TAVI rather than referring them for surgical aortic valve replacement. Although the incidence of peri-procedural acute and subacute stroke following TAVI has fallen to 2-5%, its occurrence can be life-threatening and life-changing, and every effort must be made to improve patient outcome should stroke occur. Many cardiologists would not instinctively consider the use of thrombolytic therapy for post-transfemoral TAVI ischemic stroke because of concern about the risk of major bleeding from the access site, despite it being a standard of care for ischemic stroke in other circumstances. The present case highlights the benefit of using intravenous thrombolytic therapy for an acute basilar artery thrombotic stroke after transfemoral TAVI (TF-TAVI) that would otherwise have almost certainly resulted in the patient's death. The case may also prompt interventional cardiologists to consider performing TF-TAVI under conscious sedation rather than general anesthesia, as this can result in an earlier detection of acute stroke and allow an earlier intervention with thrombolytic agents, with an improved outcome.

Confirmation of the Intracoronary Near-Infrared Spectroscopy Threshold of Lipid-Rich Plaques That Underlie ST-Segment-Elevation Myocardial Infarction.

OBJECTIVE: In a previous exploratory analysis, intracoronary near-infrared spectroscopy (NIRS) found the majority of culprit lesions in ST-segment-elevation myocardial infarction (STEMI) to contain a maximum lipid core burden index in 4 mm (maxLCBI4mm) of >400. This initial study was limited by a small sample size, enrollment at a single center, and post hoc selection of the maxLCBI4mm ≥400 threshold. This study was designed a priori to substantiate the ability of NIRS to discriminate STEMI culprit from nonculprit segments and to confirm the performance of the maxLCBI4mm ≥400 threshold. APPROACH AND RESULTS: At 2 centers in the United States and Sweden, 75 STEMI patients underwent intracoronary NIRS imaging after establishing thrombolysis in myocardial infarction 3 flow, but before stenting. Blinded core laboratory analysis defined the culprit segment as the 10-mm segment distal to the proximal angiographic culprit margin. The remaining vessel was divided into contiguous 10-mm nonculprit segments. The maxLCBI4mm of culprit segments (median [interquartile range]: 543 [273-756]) was 4.4-fold greater than nonculprit segments (median [interquartile range]: 123 [0-307]; P<0.001). Receiver-operating characteristic analysis demonstrated that maxLCBI4mm differentiated culprit from nonculprit segments with high accuracy (c-statistic=0.83; P<0.001). A threshold maxLCBI4mm ≥400 identified STEMI culprit segments with a sensitivity of 64% and specificity of 85%. CONCLUSIONS: This study substantiates the ability of NIRS to accurately differentiate STEMI culprit from nonculprit segments and confirms that a threshold maxLCBI4mm ≥400 is detected by NIRS in the majority of STEMI culprits.