Fractal geometry of culprit coronary plaque images within optical coherence tomography in patients with acute coronary syndrome vs stable angina pectoris.

The main cause of acute coronary syndrome (ACS) is plaque rupture and thrombus formation. However, it has not been fairly successful to identify vulnerable plaque to rupture using conventional parameters of intravascular imaging modalities. Fractal analysis is one of the mathematical models to examine geometrical features of picture image using a specific parameter called as fractal dimension (FD) which suggests geometric complexity of the image. This study examined FD of the optical coherence tomography (OCT)-derived images of the culprit plaque in patients with ACS vs stable angina pectoris (SAP) to evaluate the feasibility of FD for identifying vulnerable coronary plaques prone to provoke ACS distinguished from stable plaques only provoking SAP. We examined 65 cases (34 ACS patients, 31 SAP patients) in which the culprit lesion was imaged by OCT before percutaneous coronary intervention in patients with ACS and SAP. The culprit plaque lesion in the ACS group had a significantly larger mean lipid arc (203.8 ± 39.4° vs 152.3 ± 34.5°, p < 0.001) and a larger lipid plaque length (12.6 ± 5.1 mm vs 7.7 ± 2.7 mm, p < 0.001) and a thinner fibrous cap thickness (75.3 ± 22.3 µm vs 134.8 ± 53.2 µm, p < 0.001) than those in the SAP group. The prevalence of OCT-derived macrophage infiltration (Mph) in the entire culprit coronary vessel as well as that of the OCT-derived thin-cap fibroatheroma (TCFA) at the culprit lesion were significantly greater in the ACS group than those in the SAP group, respectively (Mph: 61.8% vs 35.5%, p = 0.048; TCFA: 44.1% vs 6.4%, p < 0.001). The FD of culprit plaque in the ACS group was significantly greater than in the SAP group (2.401 ± 0.073 vs 2.341 ± 0.051, p < 0.001). In multivariate regression analysis, the presence of Mph was a significant determinant of FD (regression coefficient estimate 0.049, CI 0.018-0.079, p = 0.002). The FD of OCT-derived image of culprit coronary plaque in the ACS group was significantly greater than that in the SAP group, indicating that the culprit plaque in ACS were structurally more complex. Therefore, fractal analysis of coronary OCT images might be clinically useful for identifying coronary plaques prone to provoke ACS.

Protective effect of the Impella on the left ventricular function after acute broad anterior wall ST elevation myocardial infarctions with cardiogenic shock: cardiovascular magnetic resonance imaging strain analysis.

BACKGROUND: The clinical efficacy of the Impella for high-risk percutaneous coronary intervention (PCI) and cardiogenic shock remains under debate. We thus sought to investigate the protective effects on the heart with the Impella's early use pre-PCI using cardiac magnetic resonance imaging (CMRI). METHODS: We retrospectively evaluated the difference in the subacute phase CMR imaging results (19 ± 9 days after admission) between patients undergoing an Impella (n = 7) or not (non-Impella group: n = 18 [12 intra-aortic balloon pumps (1 plus veno-arterial extracorporeal membrane oxygenation) and 6 no mechanical circulation systems]) in broad anterior ST-elevation myocardial infarction (STEMI) cases. A mechanical circulation system was implanted pre-PCI. RESULTS: No differences were found in the door-to-balloon time, peak creatine kinase, and hospital admission days between the Impella and non-Impella groups; however, the CMRI-derived left ventricular ejection fraction was significantly greater (45 ± 13% vs. 34 ± 7.6%, P = 0.034) and end-diastolic and systolic volumes smaller in the Impella group (149 ± 29 vs. 187 ± 41 mL, P = 0.006: 80 ± 29 vs. 121 ± 40 mL, P = 0.012). Although the global longitudinal peak strain did not differ, the global radial (GRS) and circumferential peak strain (GCS) were significantly higher in the IMPELLA than non-IMPELLA group. Greater systolic and diastolic strain rates (SRs) in the Impella than non-Impella group were observed in non-infarcted rather than infarcted areas. CONCLUSIONS: Early implantation of an Impella before PCIs for STEMIs sub-acutely prevented cardiac dysfunction through preserving the GRS, GCS, and systolic and diastolic SRs in the remote myocardium. This study provided mechanistic insight into understanding the usefulness of the Impella to prevent future heart failure.

Myocardial Ischemia due to Rapid Atrial Fibrillation Revealed Using the Instantaneous Wave-Free Ratio.

Instantaneous wave-free ratio (iFR) is a non-hyperemic coronary physiological index measured during the diastolic wave-free period. Although atrial fibrillation (AF) with beat-to-beat fluctuations can occur during diastole, the feasibility of iFR measurements during AF has previously been demonstrated. However, the effects of coronary circulation during AF on iFR measurements remain unknown. In addition, the pathophysiology of ischemia due to AF tachycardia requires further elucidation. We report a unique case of myocardial ischemia due to rapid AF, as indicated by the iFR pullback measurement and beat-to-beat analysis. When planning revascularization in patients with rapid AF, the ability of iFR to reflect ischemic stress due to AF tachycardia should be considered.

Impact of the COVID-19 outbreak on hospitalizations and outcomes in patients with acute myocardial infarction in a Japanese Single Center.

There are a few Japanese data regarding the incidence and outcomes of acute myocardial infarction (AMI) after the coronavirus disease 2019 (COVID-19) outbreak. We retrospectively reviewed the data of AMI patients admitted to the Nihon University Itabashi Hospital after a COVID-19 outbreak in 2020 (COVID-19 period) and the same period from 2017 to 2019 (control period). The patients' characteristics, time course of admission, diagnosis, and treatment of AMI, and 30-day mortality were compared between the two period-groups for both ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI), respectively. The AMI inpatients decreased by 5.7% after the COVID-19 outbreak. There were no differences among most patient backgrounds between the two-period groups. For NSTEMI, the time from the symptom onset to admission was significantly longer, and that from the AMI diagnosis to the catheter examination tended to be longer during the COVID-19 period than the control period, but not for STEMI. The 30-day mortality was significantly higher during the COVID-19 period for NSTEMI (23.1% vs. 1.9%, P = 0.004), but not for STEMI (9.4% vs. 8.3%, P = 0.77). In conclusion, hospitalizations for AMI decreased after the COVID-19 outbreak. Acute cardiac care for STEMI and the associated outcome did not change, but NSTEMI outcome worsened after the COVID-19 outbreak, which may have been associated with delayed medical treatment due to the indirect impact of the COVID-19 pandemic.

Diagnostic Utility of Cardiac Magnetic Resonance in Recurrent "Third Time" Myocarditis Without Electrocardiographic Changes.

A few studies have reported on recurrent myocarditis occurring more than twice in one patient. In this study, we present a recurrent "third time" acute myocarditis in a young female Japanese patient with a history of a definitive diagnosis of lymphocytic myocarditis by endomyocardial biopsy, cardiac magnetic resonance imaging (CMR), and catheter examination twice in the past. Although chest pain and an increase in the cardiac enzymes were observed the third time, no significant changes were noted in the 12-lead electrocardiogram (ECG), and a definitive diagnosis could be achieved by CMR. This case suggested that in patients with a history of myocarditis, if there is chest pain and elevated cardiac enzymes even without any changes in the 12-lead ECG, acute myocarditis should be considered, and CMR is useful for the differentiation.Only four case reports including this present case were found through the previous literatures. More than two recurrent episodes of myocarditis have been extremely rare, but all cases have typical chest symptoms and a troponin level increase, leading to a relatively benign prognosis.

Mechanical Complications of Myocardial Infarction.

In this retrospective observational study, we have examined the incidence, characteristics, and treatment of serious myocardial infarction (MI) -associated mechanical complications (MCs) occurring in Japanese patients in this era of percutaneous coronary intervention (PCI), focusing on frailty, nutrition, and clinical implication of surgery. Included were 883 patients who, having suffered an MI, had been admitted to Nihon University Hospital between January 2013 and April 2020. Fifteen (1.70%) of these patients had suffered a potentially catastrophic MC-ventricular free wall rupture (VFWR, n = 8), ventricular septal rupture (VSR, n = 6), or papillary muscle rupture (PMR, n = 1). Factors associated with the MCs were age, poor nutritional status, a high Killip class, delayed diagnosis of MI, a high lactate concentration, a low thrombolysis in myocardial infarction flow grade, and single-vessel disease. Thirty-day mortality among MC patients was 60% (9/15): 87.5% associated with VFWR, 33.3% associated with VSR and 0% associated with PMR. On adjusted multivariate analysis, occurrence of an MC was independently associated with 30-day mortality. Despite a high surgical risk (EuroSCORE II: 11.8 ± 4.7) with less frailty, 30-day mortality was lower among patients whose MC was treated surgically than among those whose MC was treated conservatively (40.0% versus 100.0%, respectively; P = 0.044).Our data suggest that surgical intervention can save patients with a life-threatening MI-associated MC and should be considered, if they are not particularly frail.

Impact of low-dose prasugrel on platelet reactivity and cardiac dysfunction in acute coronary syndrome patients requiring primary drug-eluting stent implantation: A randomized comparative study.

OBJECTIVE: The aim of this study was to compare how prasugrel and clopidogrel affect platelet aggregation reactivity, cardiac enzyme release, cardiac remodeling, and the formation of in-stent thrombi after primary percutaneous coronary intervention (PCI). BACKGROUND: The advantages of using prasugrel over clopidogrel in cardiac injury following acute coronary syndrome (ACS) remain unclear. METHODS: A total of 78 ACS patients were randomly allocated into clopidogrel (300 mg loading/75 mg maintenance) or prasugrel (20 mg loading/3.75 mg maintenance) treatment groups, followed by undergoing primary PCI. Platelet reactivity and cardiac enzymes were measured before and after primary PCI. Moreover, cardiac function was measured by ultrasound echocardiography and coronary angioscopic observation was after primary PCI up to 8 months later. RESULTS: Antiplatelet reactivity in the prasugrel treatment group reached optimal levels (P2Y12 reaction units [PRU] less than 262) immediately after the administration and was maintained even at 8 months, independently of the CYP2C19 genotype. Prasugrel treatment significantly suppressed creatine kinase elevation compared to clopidogrel treatment (median value 404 IU/L to 726 IU/L vs. 189 IU/L to 1,736 IU/L, p = 0.018 for maximum values) and reduced left ventricular mass (217.2-168.8 g in prasugrel, p = 0.045; 196.9-176.4 g in clopidogrel, p = 0.061). There were no significant differences in the incidence of in-stent attached thrombi between the two groups. CONCLUSIONS: Compared to clopidogrel, prasugrel produced a stable platelet aggregation inhibitory effect in patients with ACS regardless of CYP2C19 genotype, reduced cardiac enzyme release, and prevented cardiac remodeling after ACS.

Ventricular Septal Rupture After Recent Myocardial Infarction in the Very Elderly.

Ventricular septal rupture (VSR) is one of the fatal complications of myocardial infarction in the percutaneous coronary intervention era. A rapid diagnosis, medical and mechanical support, and surgical intervention are required for recovery and survival. In such a situation, the risk of complications associated with surgery is very high, especially in very elderly patients, in which any therapeutic strategy should be carefully discussed by the heart team. Herein, we describe two cases of VSRs after recent myocardial infarction (RMI) in very elderly patients that required debate regarding whether to perform surgery. The patients included a 93-year-old man and 89-year-old man, both of which were not highly frail before the RMI occurred. In the former case, a conservative strategy was adopted because the risk of surgery was considered, but he did not survive. On the other hand, the latter patient underwent surgery and his life was ultimately saved. Based on these two cases, we concluded that even if the patients are very old, if possible, surgical intervention should be fully considered.

Surviving Case of a Blowout-Type Left Ventricular Free Wall Rupture During Percutaneous Coronary Intervention for a Lateral Acute Myocardial Infarction.

A 76-year-old man suffering from chest pain was admitted to our hospital with a suspected acute myocardial infarction (AMI). Emergent coronary angiography revealed a totally occluded proximal left circumflex artery (LCX). During primary percutaneous coronary intervention, his blood pressure suddenly fell within seconds, and he developed pulseless electrical activity (PEA). Surprisingly, the 12-lead electrocardiogram (ECG) findings including the heart rate remained unchanged before and after the PEA, but a heart rate reduction and asystole occurred a few minutes after developing PEA. After tracheal intubation and mechanical assistance by venoarterial extracorporeal membrane oxygenation (VA-ECMO), the sudden onset of PEA appeared to be caused by cardiac tamponade due to a blowout-type left ventricular free wall rupture (BO-LVFWR) diagnosed by transthoracic echocardiography. While pericardiocentesis was performed and the drained blood was directly continuously perfused intravenously to keep the VA-ECMO flow, the patient was moved to the operation room. The surgical findings revealed a solitary BO-LVFWR due to a lateral AMI, and a direct closure was performed. Successful perioperative management, oral medication administration, and rehabilitation lead to the patient being transferred to a rehabilitation hospital without any serious cerebral damage. This case report suggested the detailed onset pattern of a BO-LVFWR followed by a rapid diagnosis by echocardiography and lifesaving treatment.

High shear stress on the coronary arterial wall is related to computed tomography-derived high-risk plaque: a three-dimensional computed tomography and color-coded tissue-characterizing intravascular ultrasonography study.

Low wall shear stress (WSS) is associated with plaque formation. However, the relationship between WSS and coronary plaque vulnerability remains unclear. Therefore, this study aimed to clarify the in vivo relationship between luminal WSS derived from three-dimensional (3D) computed tomography (CT) and plaque vulnerability within the coronary artery. Forty-three consecutive patients with ischemic heart disease and coronary stenotic lesions were enrolled and underwent coronary angiography and color-coded intravascular ultrasonography (iMap™) followed by multi-slice coronary CT angiography. CT-derived high-risk plaque was defined by specific CT characteristics, including low CT intensity (< 30 HU) and positive remodeling. The Student's t test, Mann-Whitney U test, χ2 test, repeated measures analysis of variance, and logistic and multiple regression were used for statistical analyses. CT-derived high-risk plaque (n = 15) had higher values of maximum and average shear stress than CT-derived stable plaque (474 ± 453 vs. 158 ± 138 Pa, p = 0.018; 4.2 ± 3.1 vs. 1.6 ± 1.2 Pa, p = 0.007, respectively). Compared with patients with CT-derived stable plaque, those with CT-derived high-risk plaque had a higher prevalence of necrotic and lipidic characteristics (44 ± 13 vs. 31 ± 11%, p = 0.001) based on iMap™. Multivariate logistic regression analysis showed that the average WSS and necrotic plus lipidic content were independent determinants of CT-derived high-risk plaque (average WSS: odds ratio 2.996, p = 0.014; necrotic plus lipidic content: odds ratio 1.306, p = 0.036). Our findings suggested that CT-derived high-risk plaque may coexist with high shear stress on the plaque surface.

Effect of drug-coated balloon angioplasty on in-stent restenotic coronary lesions analyzed with optical coherence tomography and serial coronary artery angioscopy.

Drug-coated balloon angioplasty (DCBA) has been recognized for its utility in preventing in-stent re-restenosis (ISR); however, imaging of the neointima immediately after treatment and during follow-up has only been described in a few case reports. This study aimed to determine the efficacy and mechanism of the DCBA using imaging studies both immediately after the DCBA and during the follow-up period. We enrolled 15 consecutive patients who underwent DCBA for in-stent restenosis (ISR). The in-stent neointimal volume was evaluated using optical coherence tomography (OCT), and the in-stent yellow grade was assessed using coronary angioscopy (CAS) immediately after DCBA and during the median follow-up period of 9 (8-15) months. The neointimal volume was significantly reduced from 77.1 ± 36.2 mm3 at baseline to 60.2 ± 23.9 mm3 immediately after DCBA (p = 0.0012 vs. baseline) and to 46.7 ± 21.9 mm3 during the follow-up (p = 0.0002 vs. post DCBA). The yellow grade of the residual plaques at the ISR lesion, which indicated plaque vulnerability, was significantly decreased in the follow-up CAG (from baseline: 1.79 ± 1.03, during the follow-up: 0.76 ± 0.82; p < 0.0001). These data suggest that DCBA may inhibit neointimal formation and provide angioscopic intimal stabilization for ISR lesions.

Comprehensive assessment of systemic arteriosclerosis in relation to the ocular resistive index in acute coronary syndrome patients.

This study aimed to investigate the relationship between ocular vascular resistance parameters, evaluated by laser speckle flowgraphy (LSFG), and systemic atherosclerosis, renal parameters and cardiac function in acute coronary syndrome (ACS) patients. We evaluated 53 ACS patients between April 2019 and September 2020. LSFG measured the mean blur rate (MBR) and ocular blowout time (BOT) and resistivity index (RI). 110 consequent patients without a history of coronary artery disease who visited ophthalmology as a control group. Significant positive correlations were observed between ocular RI and systemic parameters in ACS patients, including intima-media thickness (r = 0.34, P = 0.015), brachial-ankle pulse-wave velocity (r = 0.41, P = 0.002), cystatin C (r = 0.32, P = 0.020), and E/e' (r = 0.34, P = 0.013). Ocular RI was significantly higher in the ACS group than in the control group in male in their 40 s (0.37 ± 0.02 vs. 0.29 ± 0.01, P < 0.001) and 50 s (0.36 ± 0.02 vs. 0.30 ± 0.01, P = 0.01). We found that the ocular RI was associated with systemic atherosclerosis, early renal dysfunction, and diastolic cardiac dysfunction in ACS patients, suggesting that it could be a useful non-invasive comprehensive arteriosclerotic marker.

Clinical Importance of the LDL-C/Apolipoprotein B Ratio for Neointimal Formation after Everolimus-Eluting Stent Implantations.

AIMS: Smaller low-density lipoprotein (LDL) particle size has been suggested to result in the development of endothelial dysfunction, atherosclerosis, and in-stent restenosis (ISR); however, little is known regarding the impact of the LDL particle size on the neointima formation leading to ISR after everolimus-eluting stent (EES) implantation. METHODS: In this study, we have included 100 patients to examine the relationship between an LDL-C/apolipoprotein B (Apo B) ≤ 1.2, reportedly representing the LDL particle size, and the neointimal characteristics using optical coherence tomography (OCT) and coronary angioscopy (CAS) during the follow-up coronary angiography (CAG) period (8.8±2.5 months) after EES implantation. We divided them into two groups: LDL-C/Apo B ≤ 1.2 group (low LDL-C/Apo B group, n=53) and LDL-C/Apo B ＞1.2 group (high LDL-C/Apo B group, n=47). RESULTS: The low LDL-C/Apo B group had a significantly larger neointimal volume (12.8±5.3 vs. 10.3±4.9 mm3, p=0.021) and lower incidence of a neointimal homogeneous pattern (71 vs. 89 %), higher incidence of a neointimal heterogeneous pattern (25 vs. 9 %) (p=0.006) and higher prevalence of macrophage accumulation (9 vs. 2 %) (p=0.030) as assessed via OCT, and, as per the CAS findings, a higher prevalence of yellow grade ≥ 2 (grade 2; adjusted residual: 2.94, grade 3; adjusted residual: 2.00, p=0.017) than the high LDL-C/Apo B group. CONCLUSIONS: A low LDL-C/Apo B ratio was found to be strongly associated with neointimal proliferation and neointimal instability evidenced chronically by OCT and CAS. An LDL-C/Apo B ≤ 1.2 will be of aid in terms of identifying high-risk patients after EES implantation.

Three-Dimensional Fluid Dynamical Features of Coronary Plaque Rupture Provoking Acute Coronary Syndrome.

AIM: Coronary plaque rupture is the main cause of acute coronary syndrome (ACS), but the role of blood flow features around plaque rupture for ACS is still unknown. The present study aimed to assess the relationship between the geometric configuration of ruptured plaque and ACS occurrence using computational fluid dynamics (CFD) by moving particle method in patients with coronary artery disease. METHODS: In this study, 45 patients with coronary artery disease who underwent three-dimensional intravascular ultrasound (IVUS) and had a coronary ruptured plaque (24 plaques with provoked ACS, 21 without) were included. To compare the difference in blood flow profile around ruptured plaque between the patients with and without ACS, the IVUS images were analyzed via the novel CFD analysis. RESULTS: There were no significant differences in localized flow profile around ruptured plaque between the two groups when the initial particle velocity was 10.0 cm/s corresponded to a higher coronary flow velocity at ventricular diastole. However, when it was 1.0 cm/s corresponded to lower coronary flow velocity at ventricular systole, particles with lower velocity (0 ≤ V ≤ 5 cm/s) were more prevalent around ACS-PR ( p=0.035), whereas particles with higher velocity (10 ≤ V ≤ 20 cm/s) were more often detected in silent plaque ruptures (p=0.018). CONCLUSIONS: Three-dimensional IVUS revealed that coronary plaque rupture was a complex one with a wide variety of its stereoscopic configuration, leading to various patterns of the local coronary flow profile. A novel CFD analysis suggested that the local flow was more stagnant around ACS-provoked ruptures than in silent ones.

Bradycardia Shock Caused by the Combined Use of Carteolol Eye Drops and Verapamil in an Elderly Patient with Atrial Fibrillation and Chronic Kidney Disease.

Ophthalmic carteolol is often used to treat glaucoma. Elderly patients with atrial fibrillation (AF) and chronic kidney disease (CKD) are common among the super-elderly in Japan. Because these patients are exposed to polypharmacy, they are at a high-risk of adverse drug interactions. We herein report an elderly patient with CKD who suffered bradycardia shock after the combined use of carteolol eye drops and verapamil for glaucoma and paroxysmal AF. This case highlights the fact that eye drops have a similar systemic effect to oral drugs, and especially in elderly patients with polypharmacy, drug interactions can unwittingly lead to serious events.

Absence of coronary angioscopy-derived in-stent thrombi is associated with major bleeding events in acute myocardial infarction.

BACKGROUND AND AIMS: The optimal duration of dual antiplatelet therapy for acute myocardial infarction is controversial because the bleeding risk outweighs the thromboembolic risk. We hypothesized that an in-stent thrombus (IS-thrombus) detected by coronary angioscopy (CAS) after stent implantation would be associated with high bleeding risk. METHODS: This study included 208 patients who underwent CAS at 2 weeks after stent implantation for an acute myocardial infarction. The study was approved by the ethics committee at the Nihon University Itabashi Hospital (reference number RK-200714-10). RESULTS: In 84 patients, in whom no IS-thrombus was identified in the culprit vessel using CAS, the major bleeding event rate was significantly higher than that in patients with IS-thrombi (n = 124). However, no difference was detected in major adverse cardiovascular events (MACE; stroke, hospitalization for a non-fatal myocardial infarction/unstable angina, target lesion revascularization, and cardiovascular death). After adjustments by the propensity score based on patient characteristics, the absence of IS-thrombi remained an independent predictor of major bleeding events (hazard ratio 4.73, 95% confidence interval 2.04-11.00, p < 0.001). CONCLUSIONS: The absence of CAS-detected IS-thrombi in the subacute phase was independently associated with future major bleeding events, but not with MACE. These findings may help optimize the duration of dual antiplatelet therapy.

High Wall Shear Stress Is Related to Atherosclerotic Plaque Rupture in the Aortic Arch of Patients with Cardiovascular Disease: A Study with Computational Fluid Dynamics Model and Non-Obstructive General Angioscopy.

AIMS: Wall shear stress (WSS) has been considered a major determinant of aortic atherosclerosis. Recently, non-obstructive general angioscopy (NOGA) was developed to visualize various atherosclerotic pathologies, including in vivo ruptured plaque (RP) in the aorta. However, the relationship between aortic RP and WSS distribution within the aortic wall is unclear. This study aimed to investigate the relationship between aortic NOGA-derived RP and the stereographic distribution of WSS by computational fluid dynamics (CFD) modeling using three-dimensional computed tomography (3D-CT) angiography. METHODS: We investigated 45 consecutive patients who underwent 3D-CT before coronary angiography and NOGA during coronary angiography. WSS in the aortic arch was measured by CFD analysis based on the finite element method using uniform inlet and outlet flow conditions. Aortic RP was detected by NOGA. RESULTS: Patients with a distinct RP showed a significantly higher maximum WSS value in the aortic arch than those without aortic RP (56.2±30.6 Pa vs 36.2±19.8 Pa, p=0.017), no significant difference was noted in the mean WSS between those with and without aortic RP. In a multivariate logistic regression analysis, the presence of a maximum WSS value more than a specific value was a significant predictor of aortic RP (odds ratio 7.21, 95% confidence interval 1.78-37.1,p=0.005). CONCLUSIONS: Aortic RP detected by NOGA was strongly associated with a higher maximum WSS in the aortic arch derived by CFD using 3D-CT. The maximum WSS value may have an important role in the underlying mechanism of not only aortic atherosclerosis, but also aortic RP.