Frequency and Distribution of Sheet and Nodular Calcification in Coronary Arteries in Japanese Patients.

Whether a nodular calcification (NC), which is the precursor to intracoronary thrombosis, is focally or diffusely distributed in the coronary tree has major implications for ongoing efforts to identify. This study aimed to investigate the frequency and spatial distribution patterns of sheet calcification (SC) and NC in a 3-vessel examination of autopsied human hearts.A total of 323 coronary artery specimens from 110 cadavers were obtained from autopsy cases. After fixation and decalcification, the coronary artery trees were cut every 5 mm into 4-µm transverse cross-sections for histological assessment. An SC was defined as a plate-like calcification of > 1 quadrant of the vessel or > 3 mm in diameter, and NC as nodular calcium deposits separated by fibrin, and a deposit size > 1 mm in diameter.Of the 6,306 histological cross-sections, SCs and NCs were identified in 1,627 (26%) and 233 (4%) cross-sections, respectively. SCs and NCs had a similar distribution pattern in all 3 coronary arteries. In the left anterior descending artery (LAD), NCs were predominantly located in the proximal segment: the first 45 mm from the LAD ostium (72%) and the first 60 mm from the LAD ostium (84%), respectively. However, NCs were evenly distributed throughout the length of the coronary artery in the right coronary artery (RCA) and left circumflex artery (LCX).NCs coexisted with SCs, and tended to cluster in predictable parts within the proximal segments of the LAD, but were evenly distributed throughout the RCA and LCX in coronary arteries from cadavers.

The incidence, natural history, and predictive factors for tissue protrusion after drug-eluting stent implantation.

OBJECTIVES AND BACKGROUND: Although tissue protrusion (TP) between the stent struts after stent implantation has been implicate as a potential factor of stent failure, the incidence, natural history, and predictive factor of TP after stent implantation remains unclear. This prospective study evaluated the fate of TP after drug-eluting stent (DES) deployment using optical coherence tomography (OCT). METHOD AND RESULT: This study analyzed TP for 42 lesions after DES in which three serial OCTs, including preprocedure, postprocedure, and 1-month after the procedure were performed. TP was classified into the five groups: (a) persistent, (b) progressive, (c) healed, (d) regressive, and (e) late-acquired. Immediately after the procedure, 100 TPs in 37 lesions (88%) were identified. Of those, 53 (53%) were persistent, 3 (3%) were progressive, 20 (20%) were healed, and 24 (24%) were regressed at 1-month follow-up. Seven TPs in five patients (13%) were observed only at 1-month follow-up (late-acquired). CONCLUSION: In lesions with late-acquired TP, calcified nodule was identified as an underlying plaque morphology on preprocedural OCT. A serial OCT analysis found TP occurred not only immediately after DES implantation, but also 1-month after DES implantation.

Additional decrease in fractional flow reserve in the left anterior descending artery after hand-grip exercise during pharmacological coronary hyperemia.

Maximal hyperemia at the time of fractional flow reserve (FFR) measurement is generally induced by vasodilators, even when hyperemia at the onset of angina symptoms is caused by exercise stress. This study was designed to evaluate whether pharmacological hyperemia could be used as a substitute for exercise-induced hyperemia during FFR measurement. Twenty-two patients with angiographically intermediate stenosis in the left anterior descending artery (LAD) were prospectively enrolled. FFR measurements were repeated in the following two conditions while the pressure-wire was positioned in the same segment; (1) during pharmacological hyperemia induced by intracoronary administration of 2 mg nicorandil, (2) immediately after isotonic hand-grip exercise for 90 s (50% of maximum voluntary contraction) followed by intracoronary administration of 2 mg nicorandil. Isotonic hand-grip exercise increased systolic blood pressure (130 ± 19 versus 150 ± 22 mmHg, p < 0.001), heart rate (71 ± 11 versus 79 ± 13 bpm, p < 0.001), and cardiac output (5.1 ± 1.2 versus 5.9 ± 1.5 L/min, p < 0.001), which indicated an increased afterload on the left ventricle. After the hand-grip exercise, FFR significantly decreased from 0.86 ± 0.06 to 0.84 ± 0.06 (p < 0.001). A percent increase in systolic blood pressure and cardiac output after hand-grip exercise strongly correlated with ΔFFR (r = - 0.65, p < 0.001 and r = - 0.55, p < 0.001, respectively). An increase in cardiac output with hand-grip exercise during pharmacological hyperemia could induce an additional decrease in FFR for lesions located in the LAD.

Influence of different physiological hemodynamics on fractional flow reserve values in the left coronary artery and right coronary artery.

BACKGROUND: Although the left coronary artery (LCA) has a flow profile in that most blood flow occurs during diastole rather than systole, the right coronary artery (RCA) has a flow pattern that is less diastolic dominant. This study assessed whether coronary pressure waveforms distal to stenoses with the same fractional flow reserve (FFR) was the same between the LCA and RCA. METHODS: A total of 347 vessels from 318 patients who underwent FFR measurements were included. Conventional FFR was calculated as the ratio of the mean coronary distal pressure (Pd) to the mean aortic pressure (Pa) at maximal hyperemia. The pressure drop ratios in systole (PDRsystole) and diastole (PDRdiastole) were calculated as the sum of (Pa minus Pd) divided by the sum of Pa at the intracoronary diastolic and systolic pressure phases, respectively. RESULTS: Analysis of covariance of the regression line of correlation between conventional FFR and PDRsystole revealed that the slope was significantly greater in the RCA than in the left anterior descending artery (LAD) and left circumflex artery (LCX) (-0.765, -0.578, and -0.589, p < 0.001). On the other hand, the regression line of correlation between conventional FFR and PDRdiastole found that the slope was significantly greater in the LAD and LCX than in the RCA (-1.349, -1.318, and -1.223, p < 0.001). CONCLUSIONS: The pressure waveform distal to the stenosis differs between the LCA and RCA. In the LCA, the decrease in diastolic pressure mainly contributed to the drop in FFR, whereas in the RCA, it was the decrease in systolic pressure.

Differential influence of lesion length on fractional flow reserve in intermediate coronary lesions between each coronary artery.

OBJECTIVES: This study evaluated whether the influence of lesion length on functional significance is similar between each target artery. BACKGROUND: In the presence of a similar moderate degree of stenosis, the fractional flow reserve (FFR) in the left anterior descending coronary artery (LAD) is more often <0.80 than in the other arteries. METHODS: A total of 221 lesions with intermediate stenosis on coronary angiography that underwent FFR measurement for the evaluation of myocardial ischemia were enrolled. Quantitative coronary angiographic analysis including percent diameter stenosis and lesion length was performed. The area under the receiver operating characteristics (ROC) curve was estimated for the best cutoff value as a predictor of FFR value of ≤0.80 for each coronary artery. RESULTS: Although lesion length was similar among the lesions with an FFR >0.80 at different locations, the mean lesion length was significantly longer for lesions in the right coronary artery (RCA) with an FFR ≤0.80 than for those in the LAD and left circumflex artery (13.4 ± 3.4 vs. 8.6 ± 3.1 vs. 12.0 ± 3.7 mm, p < .001). ROC analysis demonstrated that the optimal cutoff value of lesion length for predicting an FFR ≤0.80 was 10.0 mm in the LAD (0.56 area under the curve [AUC], 48% sensitivity, and 76% specificity), whereas 13.1 mm in the RCA (0.84 AUC, 67% sensitivity, and 93% specificity). CONCLUSIONS: The impact of lesion length on myocardial ischemia is different for each coronary artery. A longer lesion length is required in the RCA than in the LAD to achieve an FFR ≤0.80.

Effect of Tofogliflozin on Systolic and Diastolic Cardiac Function in Type 2 Diabetic Patients.

PURPOSE: Recent studies have shown that sodium glucose cotransporter 2 (SGLT2) inhibitors have a favorable effect on cardiovascular events in diabetic patients. However, the underlying mechanism associated with a favorable outcome has not been clearly identified. The purpose of this study was to investigate the effect of tofogliflozin, SGLT2 inhibitor, on systolic and diastolic cardiac function in patients with type 2 diabetes mellitus (T2DM). METHODS: We enrolled 26 consecutive T2DM out-patients on glucose-lowering drugs who initiated tofogliflozin and underwent echocardiography before and ≥ 6 months after tofogliflozin administration. During this period, we also enrolled 162 T2DM out-patients taking other glucose-lowering drugs as a control group. Propensity score analysis was performed to match the patient characteristics. As a result, 42 patients (tofogliflozin group 21 patients and control group 21 patients) were finally used for analysis. Left ventricular systolic function was assessed by measuring 2D-echocardiographic left ventricular ejection fraction (LVEF) and diastolic cardiac function by pulsed wave Doppler-derived early diastolic velocity (E/e'). RESULTS: There were no significant differences in patient characteristics and echocardiographic parameters at baseline. The change in LVEF from baseline to follow-up was 5.0 ± 6.9% in the tofogliflozin group and - 0.6 ± 5.5% in the control group; difference significant, p = 0.006. The change in E/e' was - 1.7 ± 3.4 in the tofogliflozin group and 0.7 ± 4.1 in the control group; difference significant, p = 0.024. CONCLUSIONS: In addition to conventional oral glucose-lowering drugs, additional tofogliflozin administration had a favorable effect on left ventricular systolic and diastolic function in patients with T2DM.

The potential hazard of drug-eluting stent-induced coronary vasospasm causing subacute stent thrombosis: a case report.

BACKGROUND: Drug-eluting stent (DES) -induced coronary vasospasm is a well known phenomenon after stent implantation; however, the extent of this risk is still unknown. We report a case in which DES-induced severe coronary vasospasm was clinically suspected as a cause of subacute stent thrombosis (ST). CASE PRESENTATION: A 67-year-old man came to our hospital due to chest pain with mild exercise. He was diagnosed with effort angina by coronary angiography and underwent DES implantation in the mid-left ascending artery (LAD) after the administration of dual anti-platelet therapy. The procedure was uneventful, but his symptoms changed from effort angina to rest angina after stenting. Five days after the procedure, subacute ST occurred, requiring aspiration thrombectomy and balloon angioplasty. Thereafter, he continued to report early morning chest discomfort. We performed a spasm provocation test to evaluate the coronary vasomotor response; it revealed severe stent-edge spasm in the left main trunk to the LAD, except for the stented lesion, and total occlusion of the left circumflex artery. CONCLUSIONS: To our knowledge, the present case is the first report describing in-stent thrombosis secondary to stent-edge spasm. This case describes the potential hazard of DES-induced coronary vasospasm. Although there are several overlapping risk factors for ST development, we consider that stent-edge spasm also plays an important role in ST development. Therefore, we should monitor new-onset rest angina after stent implantation and carefully assess DES-induced coronary vasospasm.

Acute myocardial infarction with "wrap around" right coronary artery mimicking Takotsubo cardiomyopathy: a case report.

BACKGROUND: Takotsubo cardiomyopathy (TC) is a cardiomyopathy that shows distinctive clinical conditions first described more than 20 years ago. Because clinical features of TC mimic those of anterior acute myocardial infarction (AMI), the differential diagnosis is important in selecting the appropriate treatment strategy in the acute phase. But it was difficult to differentiate those two diseases because the TC-like findings; such as the electrocardiogram (ECG) changes and left ventricular wall motion abnormality can occur in AMI especially with the anatomical variance of the coronary artery. CASE PRESENTATION: A 63-year-old man was admitted due to sudden onset of chest pain and was in a cardiogenic shock state. His ECG showed ST-segment elevation in precordial (V2-6) and inferior leads (II, III, and aVF) and ST-segment depression in lead aVR. Blood biochemistry showed that cardiac enzymes were not elevated. Ultrasonic cardiography showed that the left ventricular apical level was akinetic, papillary muscle level was severely hypokinetic, and basal level was hyperkinetic, mimicking TC. However, coronary angiogram showed total occlusion of his right coronary artery wrapping around the cardiac apex. Successful percutaneous coronary intervention reversed his critical status. CONCLUSION: To our knowledge, the present case is the first report described AMI with wrap-around RCA, mimicking TC. Although TC is increasingly recognized as a true but relatively infrequent clinical entity, it is still important to carefully rule out obstructive coronary artery disease.

A pilot study of skin stretching and blood circulation effects of dermal suctioning in dogs.

Dermal suctioning has been reported to yield effects similar to those of cupping therapy in humans and horses, including pain reduction, increased blood circulation, improved flexibility, and healing. However, there is a dearth of reported outcomes concerning cupping or dermal suctioning in dogs. In this study, we examined the physiological effects of dermal suctioning in dogs. Employing the Medicell MINI pro8 device, dermal suctioning was applied to the dorsal surfaces of eight healthy beagle dogs for 20 min. Metrics such as body surface temperature, rectal temperature, pulse rate, respiratory rate, and skin pinch test results were gauged. Seven healthy beagle dogs were used as controls, and the same measurements were performed without dermal suctioning. The results showed a significant increase in the body surface temperature and skin pinch test results after dermal suctioning. We believe that the elimination of torsion in the blood vessels and nerves in the shallow fascia positively affected the thermoregulatory mechanism, resulting in an increase in body surface temperature, and also improving skin flexibility. Thus, dermal suctioning promotes subcutaneous blood circulation and improves skin flexibility in dogs. Further research is needed to identify the mechanisms underlying the effects of dermal suctioning and evaluate the stress in dogs caused by the implementation of the process.

Pretreatment With P2Y12 Inhibitors in ST-Segment Elevation Myocardial Infarction: Insights From the Bern-PCI Registry.

BACKGROUND: Evidence to support immediate P2Y12 inhibitor loading in ST-segment elevation myocardial infarction (STEMI) is limited. OBJECTIVES: This study sought to compare outcomes of STEMI patients receiving immediate or delayed P2Y12 inhibitor treatment. METHODS: Using data from the prospective Bern-PCI registry between 2016 and 2020, we stratified STEMI patients undergoing percutaneous coronary intervention according to time periods with different institutional recommendations regarding P2Y12 inhibitor pretreatment. In cohort 1 (October 2016-September 2018), immediate P2Y12 inhibitor treatment was recommended. In cohort 2 (October 2018-September 2020), P2Y12 inhibitor treatment was recommended after coronary anatomy was confirmed. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events (MACCEs) defined as all-cause death, recurrent myocardial infarction, stroke, or definite stent thrombosis at 30 days. Sensitivity analysis included only patients in whom these recommendations were followed. RESULTS: Cohort 1 included 1,116 patients; pretreatment was actually given in 708 (63.4%). Cohort 2 included 847 patients; pretreatment was withheld in 798 (94.2%). The mean age was 65 ± 13 years, and 24% were female. Baseline characteristics were well-balanced between groups. The median difference for P2Y12 loading to angiography was 52 minutes between cohort 1 and 2 and 100 minutes between patients receiving vs not receiving pretreatment. Rates of MACCEs were similar between cohort 1 and cohort 2 (10.1% vs 8.1%; adjusted HR: 0.91; 95% CI: 0.65-1.28; P = 0.59) and between patients receiving vs not receiving pretreatment (7.1% vs 8.4%; adjusted HR: 1.17; 95% CI: 0.78-1.74; P = 0.45). CONCLUSIONS: In this cohort study of patients with STEMI undergoing primary percutaneous coronary intervention, P2Y12 inhibitor pretreatment was not associated with improved MACCEs.

Effects of alirocumab on endothelial function and coronary atherosclerosis in myocardial infarction: A PACMAN-AMI randomized clinical trial substudy.

BACKGROUND AND AIMS: The effects of protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on endothelial function as assessed by flow-mediated dilation (FMD) in patients with acute myocardial infarction (AMI) are unknown. Therefore, we aimed to investigate the effects of the PCSK9 inhibitor alirocumab added to high-intensity statin on FMD, and its association with coronary atherosclerosis in non-infarct related arteries using intracoronary intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT). METHODS: This was a pre-specified substudy among patients recruited at Bern University Hospital, Switzerland, for the randomized-controlled, double-blind, PACMAN-AMI trial, which compared the effects of biweekly alirocumab 150 mg vs. placebo added to rosuvastatin. Brachial artery FMD was measured at 4 and 52 weeks, and intracoronary imaging at baseline and 52 weeks. RESULTS: 139/173 patients completed the substudy. There was no difference in FMD at 52 weeks in the alirocumab (n = 68, 5.44 ± 2.24%) versus placebo (n = 71, 5.45 ± 2.19%) group (difference = -0.21%, 95% CI -0.77 to 0.35, p = 0.47). FMD improved throughout 52 weeks in both groups similarly (p < 0.001). There was a significant association between 4 weeks FMD and baseline plaque burden (IVUS) (n = 139, slope = -1.00, p = 0.006), but not with lipid pool (NIRS) (n = 139, slope = -7.36, p = 0.32), or fibrous cap thickness (OCT) (n = 81, slope = -1.57, p = 0.62). CONCLUSIONS: Among patients with AMI, the addition of alirocumab did not result in further improvement of FMD as compared to 52 weeks secondary preventative medical therapy including high-intensity statin therapy. FMD was significantly associated with coronary plaque burden at baseline, but not with lipid pool or fibrous cap thickness.

Effect of High-Intensity Statin Therapy on Atherosclerosis (IBIS-4): Manual Versus Automated Methods of IVUS Analysis.

AIMS: Standard manual analysis of IVUS to study the impact of anti-atherosclerotic therapies on the coronary vessel wall is done by a core laboratory (CL), the ground truth (GT). Automatic segmentation of IVUS with a machine learning (ML) algorithm has the potential to replace manual readings with an unbiased and reproducible method. The aim is to determine if results from a CL can be replicated with ML methods. METHODS: This is a post-hoc, comparative analysis of the IBIS-4 (Integrated Biomarkers and Imaging Study-4) study (NCT00962416). The GT baseline and 13-month follow-up measurements of lumen and vessel area and percent atheroma volume (PAV) after statin induction were repeated by the ML algorithm. RESULTS: The primary endpoint was change in PAV. PAV as measured by GT was 43.95 % at baseline and 43.02 % at follow-up with a change of -0.90 % (p = 0.007) while the ML algorithm measured 43.69 % and 42.41 % for baseline and follow-up, respectively, with a change of -1.28 % (p < 0.001). Along the most diseased 10 mm segments, GT-PAV was 52.31 % at baseline and 49.42 % at follow-up, with a change of -2.94 % (p < 0.001). The same segments measured by the ML algorithm resulted in PAV of 51.55 % at baseline and 47.81 % at follow-up with a change of -3.74 % (p < 0.001). CONCLUSIONS: PAV, the most used endpoint in clinical trials, analyzed by the CL is closely replicated by the ML algorithm. ML automatic segmentation of lumen, vessel and plaque effectively reproduces GT and may be used in future clinical trials as the standard.

Effect of Alirocumab Added to High-Intensity Statin on Platelet Reactivity and Noncoding RNAs in Patients with AMI: A Substudy of the PACMAN-AMI Trial.

OBJECTIVE: The effect of the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor alirocumab on platelet aggregation among patients with acute myocardial infarction (AMI) remains unknown. We aimed to explore the effect of alirocumab added to high-intensity statin therapy on P2Y12 reaction unit (PRU) among AMI patients receiving dual antiplatelet therapy (DAPT) with a potent P2Y12 inhibitor (ticagrelor or prasugrel). In addition, we assessed circulating platelet-derived noncoding RNAs (microRNAs and YRNAs). METHODS: This was a prespecified, powered, pharmacodynamic substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in AMI patients undergoing percutaneous coronary intervention. Patients recruited at Bern University Hospital, receiving DAPT with a potent P2Y12 inhibitor, and adherent to the study drug (alirocumab or placebo) were analyzed for the current study. The primary endpoint was PRU at 4 weeks after study drug initiation as assessed by VerifyNow P2Y12 point-of-care assays. RESULTS: Among 139 randomized patients, the majority of patients received ticagrelor DAPT at 4 weeks (57 [86.4%] in the alirocumab group vs. 69 [94.5%] in the placebo group, p = 0.14). There were no significant differences in the primary endpoint PRU at 4 weeks between groups (12.5 [interquartile range, IQR: 27.0] vs. 19.0 [IQR: 30.0], p = 0.26). Consistent results were observed in 126 patients treated with ticagrelor (13.0 [IQR: 20.0] vs. 18.0 [IQR: 27.0], p = 0.28). Similarly, platelet-derived noncoding RNAs did not significantly differ between groups. CONCLUSION: Among AMI patients receiving DAPT with a potent P2Y12 inhibitor, alirocumab had no significant effect on platelet reactivity as assessed by PRU and platelet-derived noncoding RNAs.

Impact of alirocumab on plaque regression and haemodynamics of non-culprit arteries in patients with acute myocardial infarction: a prespecified substudy of the PACMAN-AMI trial.

BACKGROUND: Treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on top of statins leads to plaque regression and stabilisation. The effects of PCSK9 inhibitors on coronary physiology and angiographic diameter stenosis (DS%) are unknown. AIMS: This study aimed to investigate the effects of the PCSK9 inhibitor alirocumab on coronary haemodynamics as assessed by quantitative flow ratio (QFR) and DS% by three-dimensional quantitative coronary angiography (3D-QCA) in non-infarct-related arteries (non-IRA) among acute myocardial infarction (AMI) patients. METHODS: This was a prespecified substudy of the randomised controlled PACMAN-AMI trial, comparing alirocumab versus placebo on top of rosuvastatin. QFR and 3D-QCA were assessed at baseline and 1 year in any non-IRA ≥2.0 mm and 3D-QCA DS% >25%. The prespecified primary endpoint was the number of patients with a mean QFR increase at 1 year, and the secondary endpoint was the change in 3D-QCA DS%. RESULTS: Of 300 enrolled patients, 265 had serial follow-up, of which 193 underwent serial QFR/3D-QCA analysis in 282 non-IRA. At 1 year, QFR increased in 50/94 (53.2%) patients with alirocumab versus 40/99 (40.4%) with placebo (Δ12.8%; odds ratio 1.7, 95% confidence interval [CI]: 0.9 to 3.0; p=0.076). DS% decreased by 1.03±7.28% with alirocumab and increased by 1.70±8.27% with placebo (Δ-2.50%, 95% CI: -4.43 to -0.57; p=0.011). CONCLUSIONS: Treatment of AMI patients with alirocumab versus placebo for 1 year resulted in a significant regression in angiographic DS%, whereas no overall improvement of coronary haemodynamics was observed. CLINICALTRIALS: gov: NCT03067844.

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

BACKGROUND: The 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. OBJECTIVES: This 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. METHODS: The 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. RESULTS: Overall, 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). CONCLUSIONS: Triple 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).

Prediction of medial damage by rotational atherectomy using intravascular ultrasound.

OBJECTIVE: This study evaluated whether intravascular ultrasound (IVUS) images before rotational atherectomy (RA) can predict medial injury caused by RA burr passage in advance. METHODS: Thirty-three patients with de-novo lesions located in the left anterior descending coronary artery (LAD) who underwent IVUS before and immediately after RA were enrolled. The spatial axes of the two matched pre- and post-RA IVUS cross-sectional images were merged. The segment was considered to have medial damage when the continuity of the intimal layer was disrupted and the medial layer was in direct contact with the lumen on post-RA IVUS. RESULTS: Medial injuries on post-RA IVUS were identified in seven segments of five patients. All segments with medial injury were located near the bifurcation of the LAD and the diagonal branch, and the spatial orientations of the medial injury region were mostly distributed in the lateral side with a diagonal branch take-off. The lumen area was significantly smaller in segments with medial injury than in those without medial injury (P < 0.01). The IVUS catheter was in contact with the healthy side of the arterial wall on pre-RA IVUS images for more than 1 mm in length in all segments with medial injury. CONCLUSION: When the guidewire and IVUS catheter are close to the healthy side of the arterial wall on pre-RA IVUS images, there is a higher risk of medial injury due to the RA procedure, especially near the bifurcation of the LAD and diagonal branch.

Prediction of optimal debulking segments before rotational atherectomy based on pre-procedural intravascular ultrasound findings.

This study evaluated whether intravascular ultrasound (IVUS) examination before rotational atherectomy (RA) can predict the optimal route of passage of the RA burr along the vessel. 30 patients with calcified lesions who underwent IVUS before and immediately after RA were enrolled. IVUS analyses were performed at the minimum lumen area (MLA) site and at 0.5 mm intervals. Each IVUS cross-section was divided into 4 quadrants around the center of the lumen, and pre- and post-RA IVUS cross-section images were merged. Of 1140 cross-sections, 498 (44%) contained debulked regions. When the guidewire and IVUS were located within the same quadrant, the debulked region were distributed within the same quadrant in 96% of cross-sections. The debulked region and the guidewire were distributed within the same quadrant in 81% and the debulked region and the IVUS in 72% of cross-sections, in case the guidewire and IVUS were located in different quadrants. When the guidewire and the IVUS was apart > 1.0 mm, the debulked regions were distributed within the same quadrant as the guidewire in 100% and the IVUS in 0% of cross-sections. The position of the guidewire rather than that of the IVUS catheter on pre-RA IVUS images could predict the course of the RA burr's passage, especially when the guidewire and IVUS catheter were located apart from each other.

Diagnostic accuracy of optical coherence tomography for the identification of in-stent fibroatheroma following stent implantation: an ex vivo histological validation study.

The accurate identification of in-stent fibroatheroma by in vivo imaging is clinically important to preventing the late catch-up phenomenon after stent deployment. This study investigated the diagnostic accuracy of optical coherence tomography (OCT) for the detection of "in-stent fibroatheroma" following stent implantation. Fifty stented coronary arteries from the 31 autopsy hearts were examined to compare OCT and histological image findings. A histological in-stent fibroatheroma was defined as a neointima containing an acellular necrotic core generated by macrophage infiltration. OCT-derived in-stent fibroatheroma comprised a heterogeneous pattern with an invisible stent strut behind the low-signal-intensity region. A total of 122 matched OCT and histology cross-sections were evaluated. Using histological findings as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value for OCT-derived in-stent fibroatheroma were 100%, 99%, 80%, and 100%, respectively. The only histological finding underlying the false-positive diagnosis of OCT-derived in-stent fibroatheroma was foam cell accumulation without a necrotic core on the neointimal surface. No false-negative diagnosis of OCT for in-stent fibroatheroma was apparent in this analysis. This study demonstrated the potential capability of OCT based on stent strut visualization behind low-signal-intensity regions to discriminate in-stent fibroatheroma from other neointimal tissues.

Interobserver variability in assessments of atherosclerotic lesion type via optical frequency domain imaging.

BACKGROUND: To date, there have been no data available regarding the diagnostic performance of optical frequency domain imaging (OFDI) for in vivo histological classification of atherosclerotic lesions. This study investigated whether OFDI can be used to diagnose and classify histological atherosclerotic lesions in the coronary artery by ex vivo histological examinations. METHODS: Three-hundred-fifteen histological cross-sections from 21 autopsy hearts were matched with the OFDI images. Histological cross-sections were classified into six categories: adaptive intimal thickening (AIT), pathological intimal thickening (PIT), fibrous cap atheroma (FA), fibrocalcific plaque (FC), calcified nodule, and healed erosion/rupture. The five observers with different years of experience in the interpretation of OFDI provided a single diagnosis for the OFDI scans of each cross-section according to the aforementioned six histological categories. The diagnostic accuracy and interobserver variability of lesion types for each OFDI observer were determined using histology as the gold standard. RESULTS: The overall agreement rates between OFDI and histopathologic diagnosis for OFDI observers 1-5 were 81%, 70%, 68%, 61%, and 50% (κ values of 0.75, 0.61, 0.58, 0.49, and 0.36), respectively. Although the diagnostic accuracy of OFDI for detecting AIT and FC was excellent for all five observers, the sensitivity, and positive predictive values of OFDI for detecting PIT and FA were low in proportion to years of experience. CONCLUSION: The diagnostic accuracy of atherosclerotic tissue properties from OFDI scans correlated with the observers' years of experience, especially when lesions contained lipid components.

Tangential signal dropout artefact in optical frequency domain imaging.

BACKGROUND: Tangential signal dropout (TSD), which occurs when the optical frequency domain imaging (OFDI) beam strikes the vessel wall under a glancing angle and travels almost parallel to the vessel wall, is the most important imaging artefact leading to the erroneous diagnosis of lipid-rich plaques. AIMS: This study aimed to evaluate the OFDI artefact of TSD, which mimics the appearance of lipid-rich plaque and macrophage (Mø) infiltration. METHODS: A total of 1,019 histological cross-sections from 23 autopsy hearts were matched with the corresponding OFDI images. Of these, 232 OFDI cross-sections that contained signal-poor regions with diffuse borders were classified as lipid-rich plaques. The angle θ was calculated between the OFDI beam that strikes the edge of the luminal surface of the low-intensity region and that which strikes the surface line of the low-intensity region. RESULTS: On histological evaluation, 182 (78%) cross-sections were classified as histologically lipidic/Mø infiltration, while the remaining 50 (22%) cross-sections were classified as histologically non-lipidic/Mø infiltration. The angle θ was significantly smaller in the non-lipidic/Mø infiltration group than in the lipidic/Mø infiltration group (12±6° versus 37±14°, p<0.001). Receiver operating curve analysis revealed that the optimal cut-off value of the incident angle for predicting TSD was 23° with an area under the curve of 0.98. CONCLUSIONS: When the OFDI imaging beam strikes the tissue at an angle θ<23°, TSD artefact could occur. To eliminate image misinterpretation, our findings suggest that the OFDI catheter geometry should be considered for the accurate diagnosis of lipid-rich plaques and Mø infiltration.