Maximum Lipid Core Burden Index Research Articles

Role of Bailout Gene-Silencing Therapy in Plaque Lipid Reduction: Intravascular Imaging Study.

Introduction Insufficient statin/ezetimibe effectiveness for low-density lipoprotein cholesterol (LDL-C) reduction is not uncommon. A novel gene-silencing medication inclisiran has been introduced. Near-infrared spectroscopy (NIRS) allows to assess the dynamics of plaque lipid content in the context of optimal lipid-lowering pharmacotherapy. The aim of this study was to evaluate the impact of optimal hypolipidaemic pharmacotherapy, including add-on inclisiran, on the plasma lipid profile and plaque lipid content. Methods This study enrolled patients with stable coronary artery disease, admitted for elective percutaneous coronary intervention (PCI). NIRS of the segment of interest was performed during index PCI and 15 months later. Patients having LDL-C >1.8 mmol/l after 4-6 weeks of maximum tolerated statin/ezetimibe therapy received add-on inclisiran. Lipid profile changes within 15 months were also evaluated. Results Among 42 included patients, 24 drug resistant hypercholesterolemia participants were assigned to inclisiran therapy. After 15 months, a significant LDL-C decrease of 26.42% was established (p=0.006), with 12 participants reaching the LDL-C goal of <1.8 mmol/l. Average 15-month LDL-C reduction was 36.03%. NIRS data demonstrated a significant reduction in maximum lipid-core burden index within 4 mm (maxLCBI4 mm) in the inclisiran group (-117.64, p=0.004) and statin/ezetimibe group (-141.88, p=0.004), with no significant difference between the groups (p=0.213). Conclusion Results demonstrate an association between better LDL-C control and coronary plaque lipid burden reduction. Addition of inclisiran leads to remarkable LDL-C reduction in patients who have run out of statin and ezetimibe treatment options.

Association of Lipoprotein(a) With Changes in Coronary Atherosclerosis in Patients Treated With Alirocumab.

Elevated Lp(a) (lipoprotein[a]) is a risk marker for atherosclerotic disease, but the underlying mechanisms remain elusive. We examined the association of Lp(a) with changes in coronary atherosclerosis following intensive lipid-lowering therapy. In the PACMAN-AMI trial (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction), 300 patients with acute myocardial infarction were randomized to receive biweekly alirocumab 150 mg or placebo in addition to high-intensity statins. Patients underwent serial 2-vessel intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy in the non-infarct-related arteries at baseline and after 52 weeks. The main end points were percent atheroma volume by intravascular ultrasound, minimum fibrous cap thickness by optical coherence tomography, and maximum lipid core burden index within 4 mm (maxLCBI4mm) by near-infrared spectroscopy. A total of 265 patients had serial intravascular ultrasound data (mean age, 58±9 years; 16% women). Alirocumab resulted in greater reductions in percent atheroma volume and maxLCBI4mm, as well as a greater increase in minimum fibrous cap thickness, compared with placebo. In the alirocumab group, the reduction in maxLCBI4mm was smaller in patients with higher baseline Lp(a), defined by the highest quartile (Q4, ≥98 nmol/L; n=30), than in those with lower baseline Lp(a) (Q1-Q3, <98 nmol/L; n=99; -40.2 [-91.1 to 10.7] versus -91.4 [-113.9 to -68.9], respectively; P=0.01 after adjustment for clinically relevant baseline variables), and was comparable to the maxLBI4mm reduction in the placebo group (-37.60 [-57.40 to -17.80]; n=134). These findings were consistent when higher baseline Lp(a) was defined by cut-off values of ≥75 versus <75 nmol/L (n=35 versus 94, respectively, in the alirocumab group) and ≥125 versus <125 nmol/L (n=23 versus 106, respectively). Changes in percent atheroma volume and minimum fibrous cap thickness did not differ in relation to baseline Lp(a). In patients with acute myocardial infarction, elevated Lp(a) at baseline is associated with attenuation of plaque lipid regression despite intensive treatment with alirocumab plus high-intensity statin. This finding may explain the residual cardiovascular risk associated with high Lp(a) despite optimal control of lipid levels. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03067844.

Inclisiran-containing low-density lipoprotein cholesterol reduction effectively stabilizes atherosclerotic plaques

Abstract Background/Introduction Near-infrared spectroscopy (NIRS) allows to quantify lipid composition of coronary artery lesions. High plaque lipid content has been associated with increased adverse cardiovascular event risk. Purpose Aim of this study was to evaluate atherosclerotic plaque lipid content reduction in association with low-density lipoprotein (LDL-C) lowering on the background of intensive hypolipidaemic therapy. Methods NIRS investigation was performed in stable coronary artery disease patients having 20-50% stenosis in the proximal or middle third of a coronary artery. Segment of interest was repeatedly evaluated after 15 months. Lipid-rich plaques (LRPs) were defined as lesions with maximum lipid-core burden index within 4 mm (maxLCBI4 mm) &amp;gt;250. Study participants were taking high-intensity statin (atorvastatin 40 or 80 mg and rosuvastatin 20 or 40 mg) with or without ezetimibe for a run-in period of 4-6 weeks. Afterwards, in patients not achieving LDL-C level &amp;lt;1.8 mmol/l, add-on inclisiran was started. Baseline LDL-C was defined as the level at the time of initiation of optimal lipid-lowering therapy. Statistical significance level of 0.05 was set. Results Data of 36 patients was analyzed. Mean baseline maxLCBI4 mm was 203.9, reduced by 39.8% (-81.1, 95%CI -129.2 to -33.0) at 15-month follow-up (P=0.003). In 15 patients LRPs were detected with mean baseline maxLCBI4 mm 363.5, which was decreased by 35.8% (-130.3, 95%CI -235.0 to -25.7) (P=0.020). Mean LDL-C level at baseline was 2.5 mmol/l among all participants, lowered by 32.0% (-0.8, 95%CI -1.1 to -0.5) after 15 months of treatment (P&amp;lt;0.001). 19 patients received inclisiran in addition to high-dose statin and optional ezetimibe therapy. In 24 patients achieving LDL-C target &amp;lt;1.8 mmol/l at 15-month follow-up, a significant maxLCBI4 mm reduction from 208.5 by 48.4% (-101.0, 95%CI -169.3 to -32.7) was established (P=0.010). Among those having LDL-C &amp;gt;1.8 mmol/l, maxLCBI4 mm reduction from 194.7 by 21.2% (-41.25, 95%CI -94.7 to 12.2) was observed, however the change was not statistically significant (P=0.114). Conclusion LDL-C lowering with high-intensity hypolipidaemic therapy, including escalation to proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition, demonstrated atherosclerotic plaque stabilization by NIRS-detected lipid content decrease.

Evaluation of non-target lesions in femoropopliteal disease using near-infrared spectroscopy intravascular ultrasound imaging

Abstract Aim This study aims to assess the plaque morphology of non-target lesions, especially lipid-core-containing plaque (LCP), and compare it to target lesions using near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) in patients with femoropopliteal disease. Methods We conducted a single-center prospective observational study on 14 patients who underwent endovascular therapy for femoropopliteal disease between July 2022 and November 2023. NIRS-IVUS assessment was performed on the whole femoropopliteal arterial segment. Forty-one LCP lesions &amp;gt; maximum lipid-core burden index in any 4-mm region (max LCBI4mm) 100 were detected by NIRS-IVUS. We evaluated patient and lesion characteristics. In addition, the LCP lesions were divided into two groups, the target lesion group (n=18) and the non-target lesion group (n=23), and compared. Results Patient characteristics were notable for advanced age (76.8±6.6 years), high incidence of male (78.7%), hypertension (100%), dyslipidemia (78.6%), diabetes (64.3%), statin use (71.4%). Lipid profiles were as follows: LDL-cholesterol 85.9±26.7 mg/dl, HDL-cholesterol 48.9±12.7 mg/dl, triglyceride 138.9±80.3 mg/dl, lipoprotein(a) 19.6±16.3 mg/dl. Ten participants had LCPs in the non-target lesion (71.4%). For IVUS findings, the target lesion group had significantly longer lesion length (34.6±11.9 mm vs. 22.6±8.7 mm, p=0.001), smaller minimum lumen area (7.0±2.8 mm2 vs. 14.8±5.4 mm2, p&amp;lt;0.001), and larger plaque burden (78.0±5.0 % vs. 53.0±12.0 %, p&amp;lt;0.001) than those in the non-target lesion group. No significant differences were observed in the prevalence of calcification (target lesion group vs. non-target lesion group: 83.3 % vs. 91.3 %, p=0.64) and the extent of calcification (p=0.76). For NIRS findings, the target lesion group contained a significantly smaller proportion of LCP in the lesion length (25.9±15.7 % vs. 50.6±29.2 %, p=0.002) than the non-target lesion group. On the other hand, there were no significant differences in the value of max LCBI4mm (284.4±153.4 vs. 289.5±113.1, p=0.90) and the length of LCP lesion (9.8±9.7 mm vs. 10.7±6.9 mm, p=0.74) and distribution of LCP (p=0.08) between both groups. In addition, the number of LCPs in the target femoropopliteal artery was positively correlated with max LCBI4mm in the target femoropopliteal artery (r=0.671, p=0.008) Conclusion NIRS-IVUS findings in this study demonstrated that the non-target lesions contained LCPs to the same degree as the target lesions.

Very short-term effects of single dose of proprotein convertase subtilisin kexin 9 inhibitor therapy before percutaneous coronary intervention

Abstract Introduction Several pioneering studies have reported that continuous administration of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor reduces cardiovascular events and plaque volume on intravascular ultrasound and increase the thickness of the fibrous-cap on optical coherence tomography after 52-76 weeks.[1,2] However, the effect of PCSK9 inhibitors in very short period of time has not adequately been evaluated. Purpose This study aimed to investigate the effect of the single dose of PCSK9 inhibitor in regard to serial change of plaque composition in very short period with near-infrared spectroscopy with intravascular ultrasound (NIRS-IVUS). Methods This prospective, single arm, single-center, interventional study included 27 consecutive coronary artery disease patients (silent myocardial ischemia and stable angina) who performed NIRS-IVUS at the time of coronary angiography for diagnosis between June 2021 and August 2023. Maximal lipid-core burden index over any 4-mm segment (max-LCBI4mm) and total lipid-core burden index (T-LCBI) at the target lesions were assessed with NIRS-IVUS and they were administered evolocumab 420mg. After 2 to 6 weeks, percutaneous coronary intervention (PCI) was performed on a standby basis and repeat NIRS-IVUS were performed at PCI. Results The median max-LCBI4mm showed a significant decrease from 387 to 315 (IQR: 268 to 572 and IQR: 221 to 488, respectively; p = 0.02) in a lesion-wise analysis. The median T-LCBI also showed a significant decrease from 160 to 117 (IQR: 105 to 263 and IQR: 65 to 226, respectively; p = 0.02). Minimum lumen area and minimum lumen diameter showed no significant changes. Conclusions Single dose of PCSK9 inhibitor therapy before PCI resulted in significant degression of lipid core plaques identified by NIRS at the target lesion in very short period of time.Changes of max-LCBI4mmChanges of T-LCBI

Evaluation of nontarget lesions in femoropopliteal disease using near-infrared spectroscopy intravascular ultrasound imaging.

In coronary artery disease (CAD), lipid-core-containing plaque (LCP) in nontarget lesions detected using near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) was related to increased major adverse cardiovascular events in patients with CAD. In the endovascular therapy field, few previous studies using NIRS-IVUS revealed the presence of LCPs in severe stenotic lesions of femoropopliteal disease. This study aimed to assess the plaque morphology of nontarget lesions, especially LCPs, and compare it with that of target lesions using NIRS-IVUS in patients with femoropopliteal disease. This single-center prospective observational study included 14 patients who underwent endovascular therapy for FP disease. NIRS-IVUS assessment was performed on the entire FP arterial segment. Forty-one LCP lesions with a maximum lipid-core burden index in any 4-mm region (max LCBI4mm) > 100 were detected using NIRS-IVUS. We evaluated the patient and lesion characteristics. LCP lesions were divided into the target (n = 18) and nontarget (n = 23) lesion groups for comparison. Patient characteristics were notable for advanced age (76.8 ± 6.6 years); high proportion of males (78.7%); and high incidence of hypertension (100%), dyslipidemia (78.6%), diabetes (64.3%). Regarding NIRS findings, the target lesion group exhibited a significantly smaller proportion of LCPs concerning the lesion length (25.9 ± 15.7% vs. 50.6 ± 29.2%, p = 0.002) than the nontarget lesion group. Conversely, there were no significant differences in the value of max LCBI4mm (284.4 ± 153.4 vs. 289.5 ± 113.1, p = 0.90), length of LCP lesion (9.8 ± 9.7 mm vs. 10.7 ± 6.9 mm, p = 0.74), and distribution of LCPs (p = 0.08) between the groups. In addition, the number of LCPs in the target FP artery positively correlated with max LCBI4mm in the target FP artery (r = 0.671, p = 0.008). NIRS-IVUS findings demonstrated the presence of LCPs in nontarget lesions in patients with FP disease. Moreover, the abundance of LCPs in nontarget lesions was similar to that in target lesions in FP disease.

Detection and Stabilisation of Vulnerable Plaques in the Coronary Arteries

Vulnerable atherosclerotic plaques (AP) can be assessed by coronary artery imaging techniques. Intravascular ultrasound allows real-time assessment of the longitudinal and transverse dimensions of the vessel, the severity of its remodelling, and the size and structure of the AP. The resolution of optical coherent tomography makes it possible to accurately identify vulnerable APs according to the following characteristic parameters: a large necrotic nucleus, a thin fibrous capsule, neoangiogenesis and inflammatory changes in the AP cap. Percent atheroma volume, total atheroma volume, maximum lipid core burden index within 4 mm, minimal fibrous cap thickness, maximum lipid arc, lipid length and macrophage grade are the main characteristics of vulnerable AP. Lipid-lowering therapy (LLT) has a stabilising effect on AP. Databases searched were PubMed and Web of Science up to April 2023. In total, eight relevant articles (original clinical studies) were selected. In the ODISSEY J-IVUS study, there was a decrease of total AP volume by 3.1% in the monotherapy group and 4.8% in the combined LLT group (p=0.23). In the GLAGOV trial, atheroma volume decreased by 0.9 mm3 in the placebo group and 5.8 mm3 in the evolocumab group (p&lt;0.001). Plaque regression was observed in 64.3% of patients in the evolocumab group and 47.3% in the placebo group. The dynamics of the minimum thickness of the fibrous cap varied within 18.0–62.67 µm on combined LLT and 13.2–33.19 µm on monotherapy (PACMAN-AMI). Regression of the lipid arc was also observed in the HUYGENS study. The development of cardiovascular imaging has made it possible to expand understanding of the morphology of vulnerable AP.

Intracoronary Near-Infrared Spectroscopy to Predict No-Reflow Phenomenon During Percutaneous Coronary Intervention in Acute Coronary Syndrome

Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) can identify the lipid-rich lesions, described as high lipid-core burden index (LCBI). The aim of this study was to investigate the relationship between lipid core plaque (LCP) in the infarct-related lesion detected using NIRS-IVUS and no-reflow phenomenon during percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). We investigated 371 ACS patients who underwent NIRS-IVUS in the infarct-related lesions before PCI. The extent of LCP in the infarct-related lesion was calculated as the maximum LCBI for each of the 4-mm longitudinal segments (maxLCBI4mm) measured by NIRS-IVUS. The patients were divided into 2 groups using a maxLCBI4mm cut-off value of 400. The overall incidence of no-reflow phenomenon was 53/371 (14.3%). No-reflow phenomenon was more frequently occurred in patients with maxLCBI4mm ≥400 compared to those with maxLCBI4mm <400 (17.5% vs. 2.5%, p<0.001). After propensity score matching, multivariable logistic regression analysis demonstrated that maxLCBI4mm (odds ratio: 1.008; 95% confidence interval: 1.005 - 1.012, p<0.001) was independently associated with no-reflow phenomenon. The maxLCBI4mm of 719 in the infarct-related lesion had the highest combined sensitivity (69.8%) and specificity (72.1%) for the identification of no-reflow phenomenon. In conclusion, in patients with ACS, maxLCBI4mm in the infarct-related lesion assessed by NIRS-IVUS was independently associated with no-reflow phenomenon during PCI.

The accuracy of detailed analysis of optical coherence tomography in detection of plaque lipid content: dual-imaging study with optical coherence tomography and near-infrared spectroscopy

Background Lipid-rich plaque covered by a thin fibrous cap (FC) has been identified as a frequent morphological substrate for the development of acute coronary syndrome. Optical coherence tomography (OCT) permits the identification and measurement of the FC. Near-infrared spectroscopy (NIRS) has been approved for detection of coronary lipids. Aims We aimed to assess the ability of detailed OCT analysis to identify coronary lipids, using NIRS as the reference method. Methods In total, 40 patients with acute coronary syndrome underwent imaging of a non-culprit lesion by both NIRS and OCT. For each segment, the NIRS-derived 4 mm segment with maximal lipid core burden index (maxLCBI4mm) was assessed. OCT analysis was performed using a semi-automated method including measurement of the fibrous cap thickness (FCT) of all detected fibroatheromas. Subsequent quantitative volumetric evaluation furnished FCT, FC surface area (FC SA), lipid arc, and FC (fibrous cap) volume data. OCT features of lipid plaques were compared with maxLCBI4mm. Predictors of maxLCBI4mm >400 was assessed by using univariable and multivariable analysis. Results OCT features (mean FCT, total FC SA, FC volume, maximal, mean, and total lipid arcs) strongly correlated with the maxLCBI4mm (p = 0.012 for the mean FCT, respectively p < 0.001 for all other aforementioned features). The strongest predictors of maxLCBI4mm >400 were the maximal (p = 0.002) and mean (p = 0.002) lipid arc, and total FC SA (p = 0.012). Conclusions We found a strong correlation between the OCT-derived features and NIRS findings. Detailed OCT analysis may be reliably used for detection of the presence of coronary lipids.

Thin Calcification Predicts Lipid Component in Carotid Plaque—Relationship Between Lipid Distribution and Thin Calcification

BackgroundAccurately evaluating plaque characteristics is essential because lesions with lipid-rich plaque put patients at risk of thromboembolic complications from carotid artery stenting (CAS). Near-infrared spectroscopy (NIRS) is a diagnostic imaging modality that identifies lipid components from the near-infrared absorption pattern, but does not reveal the distribution of calcification. The purpose of this study was to investigate the calcification characteristics of unstable carotid plaques, focusing on relationships between the calcification characteristics revealed by computed tomography angiography (CTA) and the lipid core distribution derived from NIRS. MethodsParticipants in this retrospective analysis comprised 35 patients (29 men, 6 women; mean age, 76.0 years; range, 52–89 years) who underwent CAS in our institute between January 2021 and December 2022. We evaluated the thickness and length of carotid calcifications at the minimal lumen level from preoperative CTA and analyzed the relationship with maximal lipid core burden index (max-LCBI) from NIRS. ResultsStrong, negative linear correlations were observed between the thickness of calcification and max-LCBI at Area (any segment in a target lesion) (r=-0.795, p<0.001), max-LCBI at minimal lumen area (MLA) (r=-0.795, p<0.001) and LCBI at Lesion (rate of LCBI in entire plaque lesion) (r=-0.788, p<0.001), respectively. Significant negative linear correlations were observed between distribution of calcification length and max-LCBI at Area (r=-0.429, p=0.01), max-LCBI at MLA (r=-0.373, p=0.027) and LCBI at Lesion (r=-0.443, p=0.008). ConclusionsThin and ubiquitous carotid calcification was associated with LCBI values derived from NIRS indicative of carotid lipid plaque distribution, implying the possibility of predicting lesion instability.

NIRS-IVUS Assessment of OCT-Derived Healed Coronary Plaques.

Healed plaque (HP) is associated with rapid plaque growth and luminal narrowing. Thin-cap fibroatheroma (TCFA) is recognized as a precursor lesion to plaque rupture. The aim of the present study was to compare the lipid size among optical coherence tomography (OCT)-derived HP, TCFA, and thick-cap fibroatheroma (ThCFA) using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). The present study included 173 patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention. Non-culprit lesions with angiographically intermediate stenosis were assessed by both OCT and NIRS-IVUS. The frequency of TCFA, HP, and ThCFA was 35 (20%), 53 (30%), and 85 (49%), respectively. Minimum lumen area was not significantly different between TCFA and HP, but was smaller in TCFA and HP than in ThCFA (4.6 [interquartile range {IQR}: 3.5-6.4] mm2 vs. 4.3 [3.4-5.3] mm2 vs. 6.5 [4.8-8.6] mm2, P＜0.001). Plaque burden was not significantly different between TCFA and HP, but was larger in TCFA and HP than in ThCFA (72 [IQR: 66-80] % vs. 75 [67-80] % vs. 62 [54-69] %, P＜0.001). Maximum lipid core burden index in 4mm (maxLCBI4mm) was largest in TCFA, followed by HP and ThCFA (493 [IQR: 443-606] vs. 446 [347-520] vs. 231 [161-302], P＜0.001). The frequency of lipid rich plaque with maxLCBI4mm ＞400 was highest in TCFA, followed by HP and ThCFA (89% vs. 60% vs. 7%, P＜0.001). Based on NIRS-IVUS findings, non-culprit coronary HP in AMI was associated with vulnerable plaque characteristics, but not as much as TCFA.

Lowering apolipoprotein C-III associates with regression of lipidic plaque materials in type 2 DM patients with coronary artery disease: the pre-specified analysis from the OPTIMAL trial

Abstract Introduction Apolipoprotein CIII (ApoC-III) is a circulating lipoprotein which affects triglyceride-rich lipoprotein metabolism and functionality of high-density lipoproteins. These properties indicate ApoC-III as a potential contributor to atherosclerosis. The OPTIMAL randomized controlled trial (jRCT1052180152) compared the efficacy of continuous glucose monitoring guided versus HbA1c-guided glycemic control on coronary atherosclerosis in Type 2 Diabetes (T2DM) patients by using serial near-infrared spectroscopy/intravascular ultrasound (NIRS/IVUS). Given that NIRS/IVUS imaging enables to quantitatively evaluate plaque burden and its lipidic component in vivo, the OPTIMAL study provides an opportunity to elucidate the association of ApoC-III with change in quantity and quality of coronary plaques. Purpose To elucidate whether serial change in ApoC-III affects the degree of atheroma progression and lipidic plaque materials on NIRS/IVUS imaging. Methods The OPTIMAL trial has serially monitored non-culprit lesions in 94 T2DM patients receiving PCI by NIRS/IVUS imaging. Of these, 46 patients (73 lesions) were included into the current analysis. Circulating ApoC-III levels were measured at both baseline and 48 weeks. The relationships of serial change in ApoC-III with NIRS/IVUS-derived measures [total atheroma volume (TAV) and maximum lipid core burden index in a 4-mm segment (maxLCBI4mm)] were analyzed. Results All of study subjects received a statin, and high-intensity statin was used in 65.2% of them. On-treatment LDL-C and HbA1c levels were 1.9±0.5mmol/L and 7.2±0.7%, respectively. On NIRS/IVUS analysis, any regression of TAV and maxLCBI4mm was observed in 71.2 and 38.4% of analyzed lesions, respectively (Table). There was no significant relationship between change in ApoC-III and TAV regression (r=0.02, p=0.89). However, a reduction of ApoC-III was significantly associated with a greater regression of maxLCBI4mm (r=0.26, p=0.03) (Figure). Furthermore, multivariate analysis adjusting for LDL-C and high-intensity statin use demonstrated lowering ApoC-III level as an independent predictor of maxLCBI4mm regression (OR=0.83, 95%CI=0.69-0.99, p=0.04) (Table). Even in patients receiving high-intensity statin, the relationship of change in ApoC-III with regression of maxLCBI4mm still existed (Figure). Conclusion Serial NIRS/IVUS imaging revealed that a reduction of circulating ApoC-III was associated with a greater regression of maxLCBI4mm. Our findings suggest ApoC-III as an important therapeutic target to modulate lipidic plaque materials in T2DM receiving a statin.Tables

Lipid core burden in relation to the severity of calcium burden assessed by computed tomographic coronary angiography in patients with chronic coronary syndrome

Abstract Background Coronary calcium scores (CACS) obtained by computed tomographic coronary angiography (CTCA) enables a noninvasive assessment of coronary calcium burden both in a single vessel and in whole coronary tree. Although higher CACS in coronary tree is known as an atherosclerotic cardiovascular disease risk marker, coronary calcification is also known as a sign of plaque stabilization. Exploring the relationship between coronary calcification and lipid core burden may help understanding a role of calcium in coronary tree. Purpose We aimed to examine the relevance of lipid components assessed by near-infrared spectroscopy (NIRS) in accordance with different degrees of CACS assessed by preprocedural CTCA imaging. Methods We investigated consecutive patients who underwent elective percutaneous coronary intervention (PCI) and pre-PCI CTCA imaged within 3 months before PCI. Patients who had stents in target vessels and who required plaque modification before NIRS imaging were excluded. Target vessels were divided into tertiles based on target vessel CACS (CACSv) and total amount of 3-vessel CACS (CACSt), respectively. Lipid components of the target vessel were evaluated by maximum lipid core burden index in 4mm (maxLCBI4mm). MaxLCBI4mm was compared among the tertiles of CACSv and CACSt. Results A total of 95 target vessels in 95 patients were evaluated for the final dataset. CACSv categories were defined as follows: 1st tertile (CACSv &amp;lt;66), 2nd tertile (CACSv &amp;gt;66 and &amp;lt;250), and 3rd tertile (CACSv &amp;gt;250). CACSt categories were defined as showing CACSt &amp;lt;190 (1st tertile), CACSt &amp;gt;190 and &amp;lt;700 (2nd tertile), and CACSt &amp;gt;700 (3rd tertile). MaxLCBI4mm increased in proportion to an extent of CACv tertiles (306 [129-463], 280 [125-460], and 444 [345-587], Ptrend &amp;lt;0.01) and an extent of CACt tertiles (265 [99-488], 356 [202-458], and 448 [318-574], Ptrend &amp;lt;0.01). Conclusions In patients who underwent elective PCI, higher maxLCBI4mm in the PCI target vessel was associated with both higher CACS in the target vessel and total amount of 3-vessel CACS.

Predictors of residual lipid content detected by near-infrared spectroscopy after elective stenting in patients with chronic coronary syndrome

Abstract Backgrounds Residual lipid-rich plaque (LRP) in stented segments assessed by near-infrared spectroscopy (NIRS) immediately after percutaneous coronary intervention (PCI) is reportedly associated with target lesion failure. However, morphological determinants of residual LRP after elective PCI remains unknown. Purpose This single-center observational study aimed to explore morphological and procedural predictors of residual LRP after electing PCI. Methods We investigated 340 consecutive patients who underwent elective NIRS-intravascular ultrasound-guided PCI for de novo coronary lesions. Lesions requiring balloon dilatation or debulking before NIRS imaging, requiring ≥2 remote stent deployment in the vessel, being treated with drug-coated balloon, and having insufficient NIRS imaging were excluded. Maximum lipid core burden index in 4mm (maxLCBI4mm) in culprit segment both before and after PCI was assessed by NIRS. Residual LRP was defined as post-PCI maxLCBI4mm in stented lesions &amp;gt;200. Baseline clinical and morphological findings were compared between lesions with versus without residual LRP. Multivariable logistic regression analysis was performed to determine predictors of residual LRP. Results A total of 236 de novo lesions in 223 patients were included in the final dataset. After PCI, residual LRP was observed in 69 (29%) lesions. Patients with residual LRP tended to be older than those without residual LRP. Pre-PCI maxLCBI4mm in culprit lesions, plaque burden, and remodeling index were greater in lesions with residual LRP. Post-PCI minimum stent area and expansion index tended to be smaller in lesions with residual LRP. In a multivariable analysis, pre-PCI maxLCBI4mm (per 10, adjusted odds ratio [OR]:1.04; 95% confidence interval [CI]: 1.02 to 1.05; p&amp;lt;0.01) and stent expansion index (per 10%, adjusted OR: 0.80; 95%CI: 0.64 to 0.99; p=0.047) were independently predictive of residual LRP. Conclusions In patients undergoing elective PCI, greater pre-PCI maxLCBI4mm and smaller stent expansion were associated with post-PCI residual LRP.

Frequency, predictors and clinical outcomes of AMI patients with triple regression of coronary atherosclerosis: A sub-analysis of the PACMAN AMI trial

Abstract Background Recent studies have shown that coronary artery disease regression is not limited to atheroma reduction but also includes plaque stabilization in patients treated with high-intensity lipid-lowering therapy. The frequency and characteristics of patients who simultaneously show atheroma volume reduction and plaque stabilization defined as reduction in plaque lipid content and increase in fibrous cap thickness (i.e., triple regression) are unknown. Purpose This study sought to determine the percentage and determinants of both plaque volume reduction and plaque stabilization in patients with acute myocardial infarction (MI) and treated wiTh alirocumab or placebo added to high-intensity statin therapy. Methods The PACMAN-AMI trial employed serial intravascular ultrasound, near-infrared spectroscopy and optical coherence tomography to compare the effects of alirocumab vs. placebo (1:1) in 265 patients (537 non–infarct-related coronary arteries) receiving high-intensity statin therapy. Triple regression was defined by the combined presence of reduction in percent atheroma volume (PAV), reduction in maximum lipid core burden index (maxLCBI4mm) and increase in minimal fibrous cap thickness (FCT). Clinical outcomes of patients with or without triple regression were assessed at one year follow-up. Results Overall, 199 (75.1%) patients showed PAV reduction, 180 (67.7%) maxLCBI4mm reduction and 172 (77.6%) minimal FCT increase, with a total of 84 (31.7%) patients having triple regression (40.8% in the alirocumab group vs. 23.0% in the placebo group, p=0.002). The percentage of patients with triple regression was similar among the groups with PAV reduction, maxLCBI4mm reduction or minimal FCT thickening (42%, 51% or 49%, respectively, p=0.30). Similar baseline clinical features and a higher reduction in low-density lipoprotein cholesterol (LDL-C, -27.1 [37.7 to -16.6] mg/dl, p&amp;lt;0.001) and apolipoprotein B levels (-18.5 [-26.0 to -11.0] p&amp;lt;0.001) were observed patienst with vs. without triple regression. A higher reduction in PAV (-1.54 [-2.14 to -0.95] %, p&amp;lt;0.001), maxLCBI4mm (-111.24 [-140.46 to -82.02], p&amp;lt;0.001) and a higher increase in minimal FCT (56.39 [38.67 to 74.11] µm, p&amp;lt;0.001) were found in patients with triple regression. At multivariable analysis, factors independently associated with triple regression included higher baseline maxLCBI4mm (1.03, 1.01 to 1.06, p=0.013) and alirocumab treatment (2.83, 1.57 to 5.16, p=0.001). The composite clinical endpoint of death, MI and ischemia-driven revascularization occurred less frequently in patients with versus without triple regression (8.3% vs 18.2%, p=0.042). Conclusions Triple regression occurred among one third of acute AMI patients receiving high-intensity lipid lowering therapy. Alirocumab treatment and higher baseline lipid accumulation were independent predictors of triple regression. Triple regression was associated with a reduced rate of adverse cardiovascular events.

Bailout inclisiran-based triple lipid-lowering therapy reduces plaque lipid content in stable coronary artery disease patients

Abstract Background Low-density lipoprotein cholesterol (LDL-C) has a causal role in atherosclerotic cardiovascular disease. Genetic studies and variability in individual response to lipid-lowering therapies suggest combining hypolipidaemic medications with different mechanisms of action. Purpose The aim of this study was to evaluate the effect of triple inclisiran-based hypolipidaemic therapy in patients not reaching LDL-C target on maximum statin/ezetimibe treatment. Methods This prospective study enrolled 37 stable coronary artery disease patients admitted for elective percutaneous coronary intervention after 4-6 weeks on maximum tolerated statin and/or ezetimibe therapy during run-in period. Afterwards, patients with LDL-C level &amp;gt;1.8 mmol/l at the time of inclusion were assigned to receive add-on inclisiran (triple therapy group). In all participants near-infrared spectroscopy (NIRS) was performed at baseline and after 15 months for atherosclerotic plaque evaluation in the segment of interest, defined as 20-50% lesion in the proximal or middle third of a coronary artery. Statistical analysis was carried out with SPSS Statistics software. Results Average LDL-C level among screened patients was 2.81 (±1.17) mmol/l. In 19 patients LDL-C level remained &amp;gt;1.8 mmol/l on maximally tolerated statin and/or ezetimibe treatment, and after 15 months of triple therapy mean LDL-C reached 1.81 (±1.02) mmol/l with a significant LDL-C percentage change of 35.59% (95%CI -47.31 to -9.18, P=0.006) in this group. 17 patients continued statin/ezetimibe as mono or dual treatment and at 15-month follow-up mean LDL-C level comprised 1.67 (±0.61) mmol/l among these participants. According to NIRS data, maximum lipid-core burden index within 4 mm (maxLCBI4 mm) was significantly reduced by 28.85 (95%CI -189.39 to 17.64, P=0.041) in triple therapy group and by 114.72 in mono or dual therapy group (-194.76 to 23.01, P=0.004), with no statistically significant difference established between both groups (P=0.494). Conclusions Triple therapy demonstrated significant atherosclerotic plaque lipid content reduction along with LDL-C level lowering in patients with insufficient effectiveness of statin/ezetimibe treatment.

Incremental value of physiological indices to predict high-risk plaque detected by NIRS-IVUS

Abstract Background The vulnerable plaque are called high-risk plaques (HRPs), and coronary computed tomography angiography (CCTA) studies have revealed the following characteristics: (1) lesion plaque density on CT≦30HU (2) positive remodeling, (3) The presence of spotty calcification, (4) ΔFractional Flow Reserve derived from CCTA (FFRCT) or Δ Quantitative Flow Reserve (QFR)≧0.06 has been cited as a feature of these lesions. Therefore, identification of HRPs in non-culprit lesion is important to reduce future cardiovascular events. Purpose The purpose of the study was to determine whether HRP is predictable by incremental values of physiological indices in non-culprit lesions of ACS subjects. Methods A total of 137 non-culprit coronary lesions in 31 ACS subjects were retrospectively evaluated by CCTA, FFRCT, QFR and NIRS-IVUS imaging. Each coronary artery was divided into 30mm long segments beginning at the ostium to evaluate lesion vulnerability. By NIRS imaging, plaque with 4-mm maximum lipid-core burden index (maxLCBI4mm) ≥400 was defined as HRP. The relationship between HRP detected by NIRS and CCTA-derived plaque features, delta (Δ) FFRCT, and ΔQFR was evaluated. Results CT density, positive remodeling, diameter stenosis, ΔFFRCT, and ΔQFR were significantly associated with HRP, respectively (P&amp;lt;0.05). On multivariable analysis, CT density (OR; 0.95, 95%CI 0.91-0.99, P=0.0001), diameter stenosis (OR; 1.05, 95%CI 1.00-1.10, P=0.03) and ΔQFR (OR; 2119483 , 95%CI 1.75-2561856632475.6, P=0.03) independently predicted HRP, but not ΔFFRCT. ROC analysis for predicting HRP showed greater accuracy with incremental ΔQFR values in the model of CT density and diameter stenosis (AUC 0.93, P&amp;lt;0.0001). Conclusion HRP detected by NIRS may be predicted with greater accuracy by integrating QFR values with the assessment of CCTA-derived plaque features.figure1figure2

Concomitant Coronary Atheroma Regression and Stabilization in Response to Lipid-Lowering Therapy

BackgroundThe frequency, characteristics, and outcomes of patients treated with high-intensity lipid-lowering therapy and showing concomitant atheroma volume reduction, lipid content reduction, and increase in fibrous cap thickness (ie, triple regression) are unknown. ObjectivesThis study was designed to investigate rates, determinants, and prognostic implications of triple regression in patients presenting with acute myocardial infarction and treated with high-intensity lipid-lowering therapy. MethodsThe PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients with Acute Myocardial Infarction) trial used serial intravascular ultrasound, near-infrared spectroscopy, and optical coherence tomography to compare the effects of alirocumab vs placebo in patients receiving high-intensity statin therapy. Triple regression was defined by the combined presence of percentage of atheroma volume reduction, maximum lipid core burden index within 4 mm reduction, and minimal fibrous cap thickness increase. Clinical outcomes at 1-year follow-up were assessed. ResultsOverall, 84 patients (31.7%) showed triple regression (40.8% in the alirocumab group vs 23.0% in the placebo group; P = 0.002). On-treatment low-density lipoprotein cholesterol levels were lower in patients with vs without triple regression (between-group difference: −27.1 mg/dL; 95% CI: −37.7 to −16.6 mg/dL; P < 0.001). Triple regression was independently predicted by alirocumab treatment (OR: 2.83; 95% CI: 1.57-5.16; P = 0.001) and a higher baseline maximum lipid core burden index within 4 mm (OR: 1.03; 95% CI: 1.01-1.06; P = 0.013). The composite clinical endpoint of death, myocardial infarction, and ischemia-driven revascularization occurred less frequently in patients with vs without triple regression (8.3% vs 18.2%; P = 0.04). ConclusionsTriple regression occurred in one-third of patients with acute myocardial infarction who were receiving high-intensity lipid-lowering therapy and was associated with alirocumab treatment, higher baseline lipid content, and reduced cardiovascular events. (Vascular Effects of Alirocumab in Acute MI-Patients [PACMAN-AMI]; NCT03067844)

Clinical outcomes of acute myocardial infarction arising from non-lipid-rich plaque determined by NIRS-IVUS

Acute myocardial infarction (AMI) can rarely arise from non-lipid-rich coronary plaques. This study sought to compare the clinical outcomes after percutaneous coronary intervention (PCI) between AMI showing maximum lipid-core burden index in 4 mm (maxLCBI4mm) < 400 and ≥ 400 in the infarct-related lesions assessed by near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). We investigated 426 AMI patients who underwent NIRS-IVUS in the infarct-related lesions before PCI. Major adverse cardiovascular events (MACE) were defined as the composite of cardiac death, non-fatal MI, clinically driven target lesion revascularization (TLR), clinically driven non-TLR, and congestive heart failure requiring hospitalization. 107 (25%) patients had infarct-related lesions of maxLCBI4mm < 400, and 319 (75%) patients had those of maxLCBI4mm ≥ 400. The maxLCBI4mm < 400 group had a younger median age at onset (68 years [IQR: 57–78 years] vs. 73 years [IQR: 64–80 years], P = 0.007), less frequent multivessel disease (39% vs. 51%, P = 0.029), less frequent TIMI flow grade 0 or 1 before PCI (62% vs. 75%, P = 0.007), and less frequent no-reflow immediately after PCI (5% vs. 11%, P = 0.039). During a median follow-up period of 31 months [IQR: 19–48 months], the frequency of MACE was significantly lower in the maxLCBI4mm < 400 group compared with the maxLCBI4mm ≥ 400 group (4.7% vs. 17.2%, P = 0.001). MaxLCBI4mm < 400 was an independent predictor of MACE-free survival at multivariable analysis (hazard ratio: 0.36 [confidence interval: 0.13–0.98], P = 0.046). MaxLCBI4mm < 400 measured by NIRS in the infract-related lesions before PCI was associated with better long-term clinical outcomes in AMI patients.

Preventive PCI or medical therapy alone for vulnerable atherosclerotic coronary plaque: Rationale and design of the randomized, controlled PREVENT trial

Acute coronary syndromes are commonly caused by the rupture of vulnerable plaque, which often appear angiographically not severe. Although pharmacologic management is considered standard therapy for stabilizing plaque vulnerability, the potential role of preventive local treatment for vulnerable plaque has not yet been determined. The PREVENT trial was designed to compare preventive percutaneous coronary intervention (PCI) plus optimal medical therapy (OMT) with OMT alone in patients with functionally nonsignificant high-risk vulnerable plaques. The PREVENT trial is a multinational, multicenter, prospective, open-label, active-treatment-controlled randomized trial. Eligible patients have at least 1 angiographically significant stenosis (diameter stenosis >50% by visual estimation) without functional significance (fractional flow reserve [FFR] >0.80). Target lesions are assessed by intracoronary imaging and must meet at least 2 imaging criteria for vulnerable plaque; (1) minimal lumen area <4.0 mm2; (2) plaque burden >70%; (3) maximal lipid core burden index in a 4 mm segment >315 by near infrared spectroscopy; and (4) thin cap fibroatheroma as determined by virtual histology or optical coherence tomography. Enrolled patients are randomly assigned in a 1:1 ratio to either preventive PCI with either bioabsorbable vascular scaffolds or metallic everolimus-eluting stents plus OMT or OMT alone. The primary endpoint is target-vessel failure, defined as the composite of death from cardiac causes, target-vessel myocardial infarction, ischemic-driven target-vessel revascularization, or hospitalization for unstable or progressive angina, at 2 years after randomization. Enrollment of a total of 1,608 patients has been completed. Follow-up of the last enrolled patient will be completed in September 2023 and primary results are expected to be available in early 2024. The PREVENT trial is the first large-scale, randomized trial to evaluate the effect of preventive PCI on non-flow-limiting vulnerable plaques containing multiple high-risk features that is appropriately powered for clinical outcomes. PREVENT will provide compelling evidence as to whether preventive PCI of vulnerable plaques plus OMT improves patient outcomes compared with OMT alone. URL: https://www. gov. Unique identifier: NCT02316886. The PREVENT trial is the first, large-scale randomized clinical trial to evaluate the effect of preventive PCI on non-flow-limiting vulnerable plaque with high-risk features. It will provide compelling evidence to determine whether PCI of focal vulnerable plaques on top of OMT improves patient outcomes.