Automated artificial intelligence (AI)-based assessment of atherosclerosis burden applied to coronary computed tomography angiography (CCTA) can optimize image processing times, standardize interpretation, and minimize inter-observer variability. We investigated the diagnostic utility of AI-based CCTA quantification (AI-QCT) of coronary atherosclerosis in coronary segments co-registered with intravascular ultrasound (IVUS) of diseased and non-diseased segments. Patients who underwent CCTA and IVUS in the INVICTUS registry (ClinicalTrials.gov: NCT04066062) were enrolled. Images were analyzed by independent core laboratories blinded to each modality’s findings. Vessel external elastic membrane (EEM), lumen, plaque volumes, plaque burden, and percent atheroma volume (PAV) were quantified in whole co-registered segments and subsegments containing non-calcified and low-attenuation plaques. A calcium index was calculated for the whole co-registered segment. A total of 108 vessels from 85 patients were included. Pearson’s correlation demonstrated strong associations between AI-QCT and IVUS in quantifying the EEM volume (r = 0.899), lumen volume (r = 0.943), and plaque volume (r = 0.833), length-normalized PAV (r = 0.851), and calcium index (r = 0.960) in the whole-segment analysis. Strong correlations were seen for vessel, lumen, and plaque volumes in non-calcified (Pearson’s coefficient: 0.95, 0.97, and 0.83, respectively) and low-attenuation (Pearson’s coefficient: 0.90, 0.86, and 0.86, respectively) plaque segments. The minimum lumen area was 0.61 ± 1.18 mm2 (95

The mechanisms underlying cardiorenal benefits of finerenone remain unclear. This mechanistic trial aimed to evaluate the effects of finerenone on vascular stiffness, as assessed using the cardio-ankle vascular index (CAVI), and cardiorenal biomarkers in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). Eligible patients with T2D and CKD (estimated glomerular filtration rate [eGFR], 25 to < 90 mL/min/1.73 m2; urinary albumin-to-creatinine ratio [UACR], 30 to < 3500 mg/g Cr) were randomly allocated to receive either dose-adjusted finerenone or matching placebo. The primary endpoint was the change in CAVI at week 24. The key secondary endpoint was the proportional change in UACR from baseline over 24 weeks. As an exploratory analysis, changes in circulating proteins were measured by using the Olink® Target 96 Cardiovascular III and Inflammation panels. This investigator-initiated, multicentre, prospective, two-arm parallel, placebo-controlled, double-blind, randomised clinical trial was conducted at 13 sites in Japan. Among 102 patients randomised, 101 (66.3

Background and Aims The efficacy and safety of early sacubitril/valsartan (Sac/Val) initiation after acute heart failure (AHF) has not been demonstrated outside North America. The present study aimed to evaluate the effect of in-hospital Sac/Val therapy initiation after an AHF episode on N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in Japanese patients. Methods This was an investigator-initiated, multicentre, prospective, randomized, open-label, blinded-endpoint pragmatic trial. After haemodynamic stabilization within 7 days after hospitalization, eligible inpatients were allocated to switch from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to Sac/Val (Sac/Val group) or to continue angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (control group). The primary efficacy endpoint was the 8-week proportional change in geometric means of NT-proBNP levels. Results A total of 400 patients were equally randomized, and 376 (median age 75 years, 31.9% women, de novo heart failure rate 55.6%, and median left ventricular ejection fraction 37%) were analysed. The per cent changes in NT-proBNP level geometric means at Weeks 4/8 were -35%/-45% (Sac/Val group) and -18%/-32% (control group), and their group ratio (Sac/Val vs. control) was 0.80 (95% confidence interval 0.68-0.94; P = .008) at Week 4 and 0.81 (95% confidence interval 0.68-0.95; P = .012) at Week 8, respectively. In the pre-specified subgroup analyses, the effects of Sac/Val were confined to patients with a left ventricular ejection fraction < 40% and were more evident in those in sinus rhythm and taking mineralocorticoid receptor antagonists. No adverse safety signal was evident. Conclusions In-hospital Sac/Val therapy initiation in addition to contemporary recommended therapy triggered a greater NT-proBNP level reduction in Japanese patients hospitalized for AHF. These findings may expand the evidence on Sac/Val therapy in this clinical situation outside North America.

Herein, we report a case of myocarditis in a 27-year-old male with long-term follow-up using longitudinal peak systolic strain (LPSS) measurements with transthoracic echocardiography (TTE) and late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR). On admission, a predominant decrease was observed in the LPSS in the posterolateral segments of the TTE. After a period of two weeks, the values of the LPSS observed in the posterolateral segments were still slightly reduced, which is consistent with the LGE results in CMR. After a duration of 16 months, an improvement was noted in the LPSS and LGE results in all the segments. Moreover, a time-phase discrepancy was observed in the segmental longitudinal strain curve for a period of two weeks from the onset of myocarditis. However, an improvement in the discrepancy was detected after 16 months.Learning objectiveLongitudinal peak systolic strain (LPSS) on transthoracic echocardiography (TTE) has predominantly focused on diagnosing the acute phase of myocarditis. Herein, LPSS was evaluated not only in the acute phase but also in the chronic phase. Furthermore, the relationship between the results of segmental LPSS and late gadolinium enhancement was documented. We would like to emphasize the usefulness of LPSS on TTE both for identifying myocarditis and as a tool for the long-term follow-up of patients.

Acute adverse reactions to COVID-19 mRNA vaccines are a major concern, as autopsy reports indicate that deaths most commonly occur on the same day of or one day following vaccination. These acute reactions may be due to cytokine storms triggered by lipid nanoparticles (LNPs) and anaphylaxis induced by polyethene glycol (PEG), both of which are vital constituents of the mRNA-LNP vaccines. Kounis syndrome, in which anaphylaxis triggers acute coronary syndrome (ACS), may also be responsible for these cardiovascular events. Furthermore, COVID-19 mRNA-LNP vaccines encompass adjuvants, such as LNPs, which trigger inflammatory cytokines, including interleukin (IL)-1β and IL-6. These vaccines also produce spike proteins which facilitate the release of inflammatory cytokines. Apart from this, histamine released from mast cells during allergic reactions plays a critical role in IL-6 secretion, which intensifies inflammatory responses. In light of these events, early reduction of IL-1β and IL-6 is imperative for managing post-vaccine cytokine storms, ACS, and myocarditis. Corticosteroids can restrict inflammatory cytokines and mitigate allergic responses, while colchicine, known for its IL-1β-reducing capabilities, could also prove effective. The anti-IL-6 antibody tocilizumab also displays promising treatment of cytokine release syndrome. Aside from its significance for treating anaphylaxis, epinephrine can induce coronary artery spasms and myocardial ischemia in Kounis syndrome, making accurate diagnosis essential. The upcoming self-amplifying COVID-19 mRNA-LNP vaccines also contain LNPs. Given that these vaccines can cause a cytokine storm and allergic reactions post vaccination, it is crucial to consider corticosteroids and measure IL-6 levels for effective management.

Background: Despite an increased incidence of chronic heart failure (HF) and sudden cardiac death (SCD), the use of implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT) is much lower in Japan than in Western countries. The HF Indication and SCD Prevention Trial Japan (HINODE) prospectively assessed the mortality rate, appropriately treated ventricular arrhythmias (VA), and HF in Japanese patients with a higher risk of HF. Methods and Results: HINODE consisted of ICD, CRT -defibrillator (CRT -D), pacing, and non -device treatment cohorts. This subanalysis evaluated the impact of the implantation of high -voltage devices (HVD; ICD and CRT -D) in 171 Japanese patients. We compared all -cause mortality, VA, and HF events between elderly (age >70 years at study enrollment) and non -elderly HVD recipients. The estimated survival rate through 24 months in the HVD cohort was 85.8% (97.5% lower control limit 77.6%). The risk of all -cause mortality was increased for the elderly vs. non -elderly (hazard ratio [HR] 2.82; 95% confidence interval [CI] 1.01-7.91; P=0.039), but did not differ after excluding ICD patients with CRT -D indication (HR 2.32; 95% CI 0.79-6.78; P=0.11). There were no differences in VA and HF event -free rates between elderly and non -elderly HVD recipients (P=0.73 and P=0.55, respectively). Conclusions: Although elderly patients may have a higher risk of mortality in general, the benefit of HVD therapy in this group is comparable to that in non -elderly patients.

We investigated whether drug-coated balloon (DCB) treatment is effective for all de novo cases of coronary artery disease (CAD) in patients with diabetes mellitus. Furthermore, we also investigated the relationship between the degree of diabetes mellitus and clinical outcomes after DCB treatment. In this study, we included 516 consecutive patients with de novo CAD who were treated with DCB. The patients were divided into the diabetic and non-diabetic groups. Patients with diabetes mellitus were further classified into non-insulin-treated diabetes mellitus (NITDM) and insulin-treated diabetes mellitus (ITDM). The primary endpoints were major adverse cardiovascular ischemic events (MACE) and clinically driven target lesion revascularization (CD-TLR). Within a mean clinical follow-up period of 2.5 years, the incidence of MACE among patients with diabetes mellitus (22.1

Learning points for cliniciansThis case highlights small interfering RNA (siRNA) therapy in hereditary transthyretin amyloidosis and its posttreatment improvement through multimodality imaging, including 99m Tc-pyrophosphate and 123 I-metaiodobenzylguanidine ( 123 I-MIBG) scintigraphy.This is the first case report to recognize sympathetic reinnervation using 123 I-MIBG scintigraphy.Scintigraphy may serve as a sensitive marker for siRNA treatment response.

Background: Coronary plaque analysis using artificial intelligence quantitative coronary CT (AI-QCT) is a promising tool to identify coronary atherosclerosis. However, there is insufficient data on coronary atherosclerosis volume and morphology using AI-QCT in patients who are at high risk of atherosclerosis. The purpose of this study is to clarify the differences in the volume and phenotypes of coronary atherosclerosis by age and gender using AI-QCT. Methods: The INVICTUS Registry is a multi-center registry enrolling patients who clinically underwent coronary CT angiography and invasive coronary angiography with invasive imaging modalities in Japan. Patients with a history of percutaneous coronary intervention or coronary artery bypass graft were excluded in this study. Using AI-QCT, the volume, and phenotypes (calcified, non-calcified, low-density non-calcified plaque [LD-NCP]) of coronary atherosclerosis were analyzed and assessed by age (<55, 55-64, 65-74, and 75 and older) and gender. Results: A total of 982 patients were enrolled in the study. The mean age was 70.3 ± 10.8 years, 71.9% were male. Approximately two-thirds of patients had hypertension (73.3%) and dyslipidemia (71.5%), and 36.7% had diabetes. Mean total plaque volume (PV), calcified PV, non-calcified PV, and low-density PV were 745.5±529.8 mm 3 , 248.3±302.0 mm 3 , 482.2±340.6 mm 3 , and 15.0±29.4 mm 3 , respectively. The results of plaque volume and phenotypes by age are shown in the figure. Compared to those under 55 years of age, total PV increased gradually and significantly by about 10% for every 10 years of age (p=0.022). Though no significant difference was observed in non-calcified PV between the age groups (p=0.379), calcified PV progressively and significantly increases approximately 70% for every 10 years of age (p<0.001). In contrast, the low-density plaque volume showed a trend toward a significant decrease with increasing age (p=0.073). These trends did not differ by gender. Conclusion: In a large cohort of patients at high risk for atherosclerosis analyzed by AI-QCT, total coronary PV increased with age, primarily calcified PV. While no change in non-calcified PV between the age groups, LD-NCPV was likely to decrease with increasing age. These findings may contribute to the guidance for the prevention of coronary artery diseases based on coronary atherosclerosis phenotype by age and gender.

Patient 1, with giant cell myocarditis (GCM), was the first case at our hospital to present with ocular symptoms. Unfortunately, the patient died because cardiac arrest occurred before GCM could be diagnosed. In contrast, in Patient 2, our previous experience enabled us to suspect GCM earlier, based on similar ocular symptoms. Therefore, we were able to perform a myocardial biopsy and administer immunosuppressive drugs at an early stage. Thus, it is vital to understand that ocular symptoms may be indicative of GCM, and an urgent diagnosis is needed to prevent patient death.

Background: Coronary CT angiography (CCTA) is a first-line noninvasive imaging modality for evaluating coronary artery disease (CAD). Recent advances in CCTA technology enabled semi-automated detection of coronary arteries and atherosclerosis. However, there have been to date no large-scale validation studies of automated assessment of coronary atherosclerosis phenotype and coronary artery dimensions by artificial intelligence (AI) compared to current standard invasive imaging. Methods: INVICTUS registry is a multicenter, retrospective, and prospective study designed to evaluate the di-mensions of coronary arteries, as well as the characteristic, volume, and phenotype of coronary atherosclerosis by CCTA, compared with the invasive imaging modalities including intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS)-IVUS and optical coherence tomography (OCT). All patients clinically underwent both CCTA and invasive imaging modalities within three months. Results: Patients data are sent to the core-laboratories to analyze for stenosis severity, plaque characteristics and volume. The variables for CCTA are measured using an AI-based automated software and assessed independently with the variables measured at the imaging core laboratories for IVUS, NIRS-IVUS, and OCT in a blind fashion. Conclusion: The INVICTUS registry will provide new insights into the diagnostic value of CCTA for determining coronary atherosclerosis phenotype and coronary artery dimensions compared to IVUS, NIRS-IVUS, and OCT. Our findings will potentially shed new light on precision medicine informed by an AI-based coronary CTA assessment of coronary atherosclerosis burden, composition, and severity. (ClinicalTrials.gov: NCT04066062).

The number of TV-PM implantations in elderly people is increasing. Although frailty syndrome is common in elderly patients, the relationship between the pre-procedural frailty status and clinical outcomes has not been fully elucidated in elderly TV-PM recipients.This study included 103 consecutive patients over 80 years old who were newly implanted with a TV-PM (age 85.7 ± 4.2, 41.7% male). We assessed the relationship between the clinical outcome and predictive factors, especially for the pre-procedural frailty status after the TV-PM implantation. The pre-procedural frailty status was retrospectively assessed from the medical records and classified on the basis of impairments in 3 domains (walking, cognition, and activities of daily living). The primary endpoint was defined as a heart failure admission.During the follow-up period (4.1 ± 2.3 years), 20 patients (19.4%) met the primary endpoint. Frailty syndrome was identified in 40 patients (38.8%). In univariate analysis, the LVEF (HR 0.97, 95% CI 0.96-1.00 P = 0.0492), an RV pacing burden over 40% (HR 1.58, 95% CI 1.00-2.54 P = 0.0473), and presence of a frailty status (HR 1.82, 95% CI 1.13-2.87 P = 0.0134) were found to be statistically significant predictors for the study endpoint. In multivariate analysis, having frailty syndrome was the only predictive factor for a heart failure admission (HR 1.83, 95% CI 1.12-2.93 P = 0.0157).The presence of frailty syndrome and incidence of clinical events were high and a pre-procedural frailty status assessment was key in determining the clinical outcomes in TV-PM recipients over 80 years old.

Introduction: By near-infrared spectroscopy (NIRS), plaques with 4-mm maximum lipid-core burden index (maxLCBI4 mm ) ≥400 are lipid-rich plaques. By CCTA, high-risk plaques are defined by presence of low-density non-calcified plaque (LD-NCP) and positive remodeling (PR) >1.1. Hypothesis: Artificial intelligence-enabled quantitative CT (AI-QCT) will enable identification of lipid-rich plaques when compared to NIRS reference standard. Methods: 128 atherosclerotic plaques from 47 patients were prospectively enrolled. MaxLCBI 4mm (cutoff was defined as 400) and LD-NCP derived from AI-QCT (Cleerly LABS, Denver CO) were compared. We also analyzed vessel area, plaque burden, minimal lumen area and plaque length between intravascular ultrasound (IVUS) and AI-QCT. Results: Amongst 128 plaques evaluated, maxLCBI 4mm ≥400 was 26 plaques (20.3%). Use of current LD-NCP (<30 Hounsfield threshold (HU) and LD-NCP volume >0 mm 3 ) and PR ≥1.1, yielded a sensitivity, specificity, positive and negative predictive value and accuracy of 100%, 28%, 26%, 99%, and 43%. LD-NCP volume threshold was identified from AUC as 1.8 mm 3 . With LD-NCP volume ≥1.8 mm 3 , the performance of AI-QCT was improved to 92%, 87%, 65%, 98% and 88%, respectively (Figure 1). We noted very good to excellent correlation between AI-QCT and IVUS for vessel area (R2 =0.776), plaque burden (0.699), minimal lumen area (0.815) and plaque length (0.844). Conclusions: The current CCTA definition of NIRS-verified lipid-rich plaques has limited specificity and accuracy; use of a LD-NCP volume threshold, enabled only by AI-QCT, substantially improves performance for detection and characterization.

Background: Definitions of cardiac sarcoidosis (CS) differ among guidelines. Any systemic histological finding of CS is essential for the diagnosis of CS in the 2014 Heart Rhythm Society statement, but not necessary in the Japanese Circulation Society 2016 guidelines. This study aimed to reveal the differences in outcomes by comparing 2 groups, namely CS patients with or without systemic histologically proven granuloma. Methods and Results: This study retrospectively included 231 consecutive patients with CS. CS with granulomas in ≥1 organs was diagnosed in 131 patients (Group G), whereas CS without any granulomas was diagnosed in the remaining 100 patients (Group NG). Left ventricular ejection fraction (LVEF) was significantly reduced in Group NG compared with Group G (44±13% vs. 50±16%, respectively; P=0.001). However, Kaplan-Meier curves showed that major adverse cardiovascular events (MACE)-free survival outcomes were comparable between the 2 groups (log-rank P=0.167). Univariable analyses showed that significant predictors of MACE were Groups G/NG, histological CS, LVEF, and high B-type natriuretic peptide (BNP) or N-terminal pro BNP concentrations, but none of these was significant in multivariable analyses. Conclusions: Overall risks of MACE were similar between the 2 groups despite different manifestations in cardiac dysfunction. The data not only validate the prognostic value of non-invasive diagnosis of CS, but also show the need for careful observation and therapeutic strategy in patients with CS without any granuloma.