Nitesh Nerlekar

Transluminal Attenuation Gradient in Coronary Computed Tomography Angiography Is a Novel Noninvasive Approach to the Identification of Functionally Significant Coronary Artery Stenosis: A Comparison With Fractional Flow Reserve

OBJECTIVE The purpose of this study was to assess the diagnostic accuracy of TAG320 in predicting functional stenosis severity evaluated by fractional flow reserve (FFR). BACKGROUND Coronary computed tomography angiography (CCTA) has limited specificity for predicting functionally significant stenoses. Recent studies suggest that contrast gradient attenuation along an arterial lesion, or transluminal attenuation gradient (TAG), may provide assessment of functional significance of coronary stenosis. The use of 320-detector row computed tomography (CT), enabling near isophasic, single-beat imaging of the entire coronary tree, may be ideal for TAG functional assessment of a coronary arterial stenosis. METHODS We assessed the diagnostic accuracy of TAG320 using 320-row CCTA with FFR for the evaluation of functional stenosis severity in consecutive patients undergoing invasive coronary angiography and FFR for stable chest pain. The luminal radiological contrast attenuation (Hounsfield units [HU]) was measured at 5-mm intervals along the artery from ostium to a distal level where the cross-sectional area decreased to <2.0 mm(2). TAG320 was defined as the linear regression coefficient between luminal attenuation and axial distance. Functionally significant coronary stenosis was defined as ≤0.8 on FFR. RESULTS In our cohort of 54 patients (age 62.7 ± 8.7 years, 35 men, 78 vessels), TAG320 in FFR-significant vessels was significantly lower when compared with FFR nonsignificant vessels (-21 [-27; -16] vs. -11 [-16; -3] HU/10 mm, p < 0.001). On receiver-operating characteristic analysis, a retrospectively determined TAG320 cutoff of -15.1 HU/10 mm predicted FFR ≤0.8 with (a bootstrapped resampled) a sensitivity of 77%, specificity of 74%, positive predictive value of 67%, and negative predictive value of 86%. The combined TAG320 and CCTA assessment had an area under the curve of 0.88. There was incremental value of adding TAG320 to CCTA assessment for detection of significant FFR by Wald test (p = 0.0001) and integrated discrimination improvement index (0.11, p = 0.002). CONCLUSIONS Assessment of TAG320 with a 320-detector row CT provides acceptable prediction of invasive FFR and may provide a noninvasive modality for detecting functionally significant coronary stenoses. Combined TAG320 and CCTA assessment may have incremental predictive value over CCTA alone for detecting functionally significant coronary arterial stenoses; however, larger studies are required to determine the benefit of combined TAG320 and CCTA assessment.

Percutaneous Coronary Intervention Using Drug-Eluting Stents Versus Coronary Artery Bypass Grafting for Unprotected Left Main Coronary Artery Stenosis: A Meta-Analysis of Randomized Trials

Background—Current guidelines suggest that coronary artery bypass grafting (CABG) should be the preferred revascularization method for unprotected left main coronary artery stenosis. In light of evidence from recent randomized trials, we assessed whether percutaneous coronary intervention (PCI) using drug-eluting stents is as safe and effective as CABG for the treatment of unprotected left main coronary artery disease. Methods and Results—Digital databases and manual searches were performed for randomized trials comparing PCI and CABG for unprotected left main coronary artery stenosis. Among 3887 potentially relevant studies, 5 met inclusion criteria. The primary safety end point was defined as the composite of all-cause death, myocardial infarction, or stroke. Secondary end points included a clinical effectiveness composite, which was defined as all-cause death, myocardial infarction, stroke, or repeat revascularization. Summary estimates were obtained using random-effects modeling. In total, 4594 patients were included in the analysis. There was no significant difference in the primary safety end point between the revascularization strategies (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.79–1.17; P=0.73). However, when compared with CABG, PCI was less effective (OR, 1.36; 95% CI, 1.18–1.58; P<0.001) because of significantly higher rates of repeat revascularization (OR, 1.85; 95% CI, 1.53–2.23; P<0.001). The incidence of all-cause death (OR, 1.03; 95% CI, 0.78–1.35; P=0.61), myocardial infarction (OR, 1.46; 95% CI, 0.88–2.45; P=0.08), and stroke (OR, 0.88; 95% CI, 0.39–1.97; P=0.53) did not differ between PCI and CABG. Conclusions—PCI using drug-eluting stents and CABG are equally safe methods of revascularization for patients at low surgical risk with significant unprotected left main coronary artery stenosis. However, CABG is associated with significantly lower rates of repeat revascularization.

Acute Chest Pain Investigation: Utility of Cardiac CT Angiography in Guiding Troponin Measurement

PURPOSE To assess the impact on length of stay and rate of major adverse cardiovascular events of a cardiac computed tomographic (CT) angiography-guided algorithm to examine patients who present to the emergency department (ED) with low- to intermediate-risk chest pain. MATERIALS AND METHODS The study was approved by the institutional review board, and all patients gave written informed consent. Two hundred three consecutive patients (mean age, 55 years ± 11 [standard deviation]; 123 men) with low- to intermediate-risk ischemic-type chest pain were prospectively enrolled. Patients underwent initial cardiac CT angiography with subsequent treatment determined by reference to findings at cardiac CT angiography; patients without overt plaque were immediately discharged from the hospital, patients with nonobstructive plaque and mild-to-moderate stenoses were discharged after a negative 6-hour troponin level, and patients with severe stenoses were admitted to the hospital. Discharged patients were followed up for a mean of 14.2 months. Additionally, length of stay and safety outcomes among these patients were compared with those in 102 consecutive patients with low- to intermediate-risk chest pain who presented to the ED and underwent a standard of care (SOC) work-up without cardiac CT angiography. One-way analysis of variance with Bonferroni correction was used to compare length of stay between groups. RESULTS Cardiac CT angiography findings in the 203 patients who underwent cardiac CT angiography were as follows: Sixty-five (32%) patients had no plaque, 107 (53%) had nonobstructive plaque, and 31 (15%) had severe stenoses. At follow-up, there were no deaths or cases of acute coronary syndrome (cardiac CT angiography, 0%, 95% confidence interval [CI]: 0%, 1.85%; SOC, 0%, 95% CI: 0%, 3.63%), and the rate of readmission to the hospital because of chest pain was higher with the SOC approach (9% vs 1%, P = .01). Mean ED length of stay was lower with cardiac CT angiography (6.62 hours ± 0.38 after a single troponin level and 9.15 hours ± 0.30 after serial troponin levels) than with the SOC approach (11.62 hours ± 0.47, P < .001). CONCLUSION Tailoring troponin measurement to cardiac CT angiography findings is safe and allows early discharge of patients with low- to intermediate-risk chest pain, resulting in reduced length of stay.

Plaque Structural Stress Estimations Improve Prediction of Future Major Adverse Cardiovascular Events After Intracoronary Imaging

Background—Although plaque rupture is responsible for most myocardial infarctions, few high-risk plaques identified by intracoronary imaging actually result in future major adverse cardiovascular events (MACE). Nonimaging markers of individual plaque behavior are therefore required. Rupture occurs when plaque structural stress (PSS) exceeds material strength. We therefore assessed whether PSS could predict future MACE in high-risk nonculprit lesions identified on virtual-histology intravascular ultrasound. Methods and Results—Baseline nonculprit lesion features associated with MACE during long-term follow-up (median: 1115 days) were determined in 170 patients undergoing 3-vessel virtual-histology intravascular ultrasound. MACE was associated with plaque burden ≥70% (hazard ratio: 8.6; 95% confidence interval, 2.5–30.6; P<0.001) and minimal luminal area ⩽4 mm2 (hazard ratio: 6.6; 95% confidence interval, 2.1–20.1; P=0.036), although absolute event rates for high-risk lesions remained <10%. PSS derived from virtual-histology intravascular ultrasound was subsequently estimated in nonculprit lesions responsible for MACE (n=22) versus matched control lesions (n=22). PSS showed marked heterogeneity across and between similar lesions but was significantly increased in MACE lesions at high-risk regions, including plaque burden ≥70% (13.9±11.5 versus 10.2±4.7; P<0.001) and thin-cap fibroatheroma (14.0±8.9 versus 11.6±4.5; P=0.02). Furthermore, PSS improved the ability of virtual-histology intravascular ultrasound to predict MACE in plaques with plaque burden ≥70% (adjusted log-rank, P=0.003) and minimal luminal area ⩽4 mm2 (P=0.002). Plaques responsible for MACE had larger superficial calcium inclusions, which acted to increase PSS (P<0.05). Conclusions—Baseline PSS is increased in plaques responsible for MACE and improves the ability of intracoronary imaging to predict events. Biomechanical modeling may complement plaque imaging for risk stratification of coronary nonculprit lesions.

Identification of concomitant ruptured plaque and intracoronary thrombus by optical coherence tomography

A 74-year-old man was admitted with a non-ST segment elevation myocardial infarction with no localising electrocardiogram changes. Coronary angiography showed a severe eccentric stenosis with possible overlying thrombus in a moderate caliber fi rst diagonal artery, and severe stenosis in proximal left anterior descending artery. Optical coherence tomography (OCT) was done to assess whether the stenosis in the fi rst diagonal artery was the culprit stenosis. A ruptured thin cap fi brous atheroma with overlying thrombus was identifi ed in the fi rst diagonal artery, showing an actively developing acute coronary syndrome (fi gure). The lesion was successfully stented, and excellent stent apposition was confi rmed on OCT. OCT in this case allowed identifi cation of plaque rupture and many of the high-risk features including type of plaque (fi brous, fi brocalcifi c, and lipid), erosion, thin cap fi brous atheroma, and intracoronary thrombus. Lancet 2014; 383: e11

Association of epicardial adipose tissue and high-risk plaque characteristics: A systematic review and meta-analysis

Background Epicardial adipose tissue (EAT) is hypothesized to alter atherosclerotic plaque composition, with potential development of high‐risk plaque (HRP). EAT can be measured by volumetric assessment (EAT‐v) or linear thickness (EAT‐t). We performed a systematic review and random‐effects meta‐analysis to assess the association of EAT with HRP and whether this association is dependent on the measurement method used. Methods and Results Electronic databases were systematically searched up to October 2016. Studies reporting HRP by computed tomography or intracoronary imaging and studies measuring EAT‐v or EAT‐t were included. Odds ratios were extracted from multivariable models reporting the association of EAT with HRP and described as pooled estimates with 95% confidence intervals (CIs). Analysis was stratified by EAT measurement method. Nine studies (n=3772 patients) were included with 7 measuring EAT‐v and 2 measuring EAT‐t. Increasing EAT was significantly associated with the presence of HRP (odds ratio: 1.26 [95% CI, 1.11–1.43]; P<0.001). Patients with HRP had higher EAT‐v than those without (weighted mean difference: 28.3 mL [95% CI, 18.8–37.8 mL]; P<0.001). EAT‐v was associated with HRP (odds ratio: 1.19 [95% CI, 1.06–1.33]; P<0.001); however, EAT‐t was not (odds ratio: 3.09 [95% CI, 0.56–17]; P=0.2). Estimates remained significant when adjusted for small‐study effect bias (odds ratio: 1.13 [95% CI, 1.03–1.28]; P=0.04). Conclusions Increasing EAT is associated with the presence of HRP, and patients with HRP have higher quantified EAT‐v. The association of EAT‐v with HRP is significant compared with EAT‐t; however, a larger scale study is still required, and further evaluation is needed to assess whether EAT may be a potential therapeutic target for novel pharmaceutical agents. Clinical Trial Registration URL: https://www.crd.york.ac.uk/. Unique identifier: CRD42017055473.

Midterm Safety and Efficacy of ABSORB Bioresorbable Vascular Scaffold Versus Everolimus-Eluting Metallic Stent: An Updated Meta-Analysis

One of the principal aims in developing bioresorbable vascular scaffolds (BVS) was reduction in the long-term risk of stent-related complications, including very late (>1 year) stent thrombosis (ST). However, recent data suggest that the risk of very late ST may persist, or even be increased, in BVS

Imaging of coronary atherosclerosis in various susceptible groups

Coronary artery disease (CAD) is the leading cause of death and disability worldwide. Atherosclerosis, which is the primary pathophysiologic mechanism for the development of plaque leading to CAD, is a multifactorial process resulting from a complex interplay between genetic susceptibility and various risk factors such as hypertension (HT), dyslipidaemia, diabetes mellitus (DM) and smoking. In addition, influences from other disease states such as chronic kidney disease (CKD), obesity and the metabolic syndrome as well as gender and ethnic diversity also contribute to the disease process. Insights from pathological observations and advances in cellular and molecular biology have helped us understand the process of plaque formation, progression and rupture leading to events. Several intravascular imaging techniques such as intravascular ultrasound (IVUS), Virtual histology IVUS (VH-IVUS) and optical coherence tomography (OCT) allow in vivo assessment of plaque burden, plaque morphology and response to therapy. In addition, non invasive assessment using coronary artery calcium (CAC) score allows risk stratification and plaque burden assessment whilst computed tomography coronary angiography (CTCA) allows evaluation of luminal stenosis, plaque characterisation and quantification. This review aims to summarise the results of invasive and non-invasive imaging studies of coronary atherosclerosis seen in various high-risk populations including DM, metabolic syndrome, obesity, CKD and, gender differences and ethnicity. Understanding the phenotype of plaques in various susceptible groups may allow potential development of personalised therapies.

The ASLA Score: A CT Angiographic Index to Predict Functionally Significant Coronary Stenoses in Lesions with Intermediate Severity-Diagnostic Accuracy.

PURPOSE To identify computed tomographic (CT) coronary indexes independently associated with a fractional flow reserve (FFR) of 0.8 or less, to derive a score that combines CT indexes most predictive of an FFR of 0.8 or less, and to evaluate the diagnostic accuracy of the score in predicting an FFR of 0.8 or less. MATERIALS AND METHODS This retrospective study had institutional review board approval and waiver of the need to obtain informed consent. Consecutive patients who underwent CT coronary angiography and FFR assessment with one or more discrete lesion(s) of intermediate (30%-70%) severity at CT were included. Quantitative CT measurements were performed by using dedicated software. The CT indexes evaluated included the following: plaque burden, minimal luminal area and diameter, stenosis diameter, area of stenosis, lesion length, remodeling index, plaque morphology, calcification severity, and the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) score, which approximates the size of the myocardium subtended by a lesion. By using covariates independently associated with an FFR of 0.8 or less, a score was determined on the basis of modified Akaike information criteria, and the C statistics of individual and combined indexes were compared. RESULTS Eighty-five patients (mean age, 64.2 years; range, 48-88 years; 65.9% men; 124 lesions; 38 lesions with an FFR ≤ 0.8) were included. Area of stenosis, lesion length, and APPROACH score were the strongest predictors of an FFR of 0.8 or less and were used to derive the ASLA score. The optimism-adjusted Harrell C statistic for the combined score was 0.82, which was superior to that for area of stenosis (0.74), lesion length (0.75), and the APPROACH score (0.71) (P < .001 for trend). The corresponding incremental discrimination improvement indexes were 0.17, 0.11, and 0.19, respectively (P < .001 for all), suggesting that the score improves reclassification compared with any one angiographic index. The average time required for score derivation was 102.6 seconds. CONCLUSION The ASLA score, which accounts for CT-derived area of stenosis, lesion length, and APPROACH score, may conveniently improve the prediction, beyond individual indexes, of functionally significant intermediate coronary lesions.

Intravascular ultrasound guidance improves clinical outcomes during implantation of both first- and second-generation drug-eluting stents: a meta-analysis

AIMS Our aim was to assess whether intravascular ultrasound (IVUS) improves clinical outcomes during implantation of first- and second-generation drug-eluting stents (DES). IVUS guidance is associated with improved clinical outcomes during DES implantation, but it is unknown whether this benefit is limited to either first- or second-generation devices. METHODS AND RESULTS MEDLINE, EMBASE and PubMed were searched for studies comparing outcomes between IVUS- and angiography-guided PCI. Among 909 potentially relevant studies, 15 trials met the inclusion criteria. The primary endpoint was MACE, defined as death, myocardial infarction, target vessel/lesion revascularisation (TVR/TLR) or stent thrombosis (ST). Summary estimates were obtained using Peto modelling. In total, 9,313 patients from six randomised trials and nine observational studies were included. First-generation DES were implanted in 6,156 patients (3,064 IVUS-guided and 3,092 angiography-guided) and second-generation in 3,157 patients (1,528 IVUS-guided and 1,629 angiography-guided). IVUS guidance was associated with a significant reduction in MACE (odds ratio [OR] 0.73, 95% CI: 0.64-0.85, p<0.001), across both first- (OR 0.79, 95% CI: 0.67-0.92, p=0.01) and second-generation DES (0.57, 95% CI: 0.43-0.77, p<0.001). For second-generation DES, IVUS guidance was associated with significantly lower rates of cardiac death (OR 0.33, 95% CI: 0.14-0.78, p=0.02), TVR (OR 0.47, 95% CI: 0.28-0.79, p=0.006), TLR (OR 0.61, 95% CI: 0.42-0.90, p=0.01) and ST (OR 0.31, 95% CI: 0.12-0.78, p=0.02). Cumulative meta-analysis highlighted progressive temporal benefit towards IVUS-guided PCI to reduce MACE (OR 0.60, 95% CI: 0.48-0.75, p<0.001). CONCLUSIONS IVUS guidance is associated with a significant reduction in MACE during implantation of both first- and second-generation DES platforms. These data support the use of IVUS guidance in contemporary revascularisation procedures using second-generation DES.