Background Coronary vasospasm is a major cause of ischemia with nonobstructive coronary arteries; however, its long-term structural and energetic consequences on the myocardium remain under-recognized. Case Summary A 72-year-old postmenopausal woman presented with chest discomfort and electrocardiographic findings suggestive of myocardial ischemia. Acetylcholine provocation testing revealed epicardial and microvascular coronary spasm. Cardiac magnetic resonance revealed focal late gadolinium enhancement in the interventricular septum, confirming replacement fibrosis mimicking hypertrophy. Additionally, the patient showed a supranormal ejection fraction of 79% and a markedly reduced end-systolic volume, indicating a hyperdynamic small left ventricle. Discussion This case demonstrates that recurrent coronary spasm is not benign and can be related to irreversible myocardial fibrosis and maladaptive hyperdynamic remodeling, increasing the risk of diastolic dysfunction and heart failure. Take Home Messages Recurrent coronary spasm may contribute to focal myocardial fibrosis. Left ventricular ejection fraction should be interpreted with end-systolic volume to identify hyperdynamic states.

BACKGROUND:Coronary spastic angina (CSA) is a functional coronary disorder causing recurrent ischemia without significant atherosclerosis, but the interaction between metabolic and inflammatory abnormalities remains unclear. OBJECTIVES:The purpose of this study was to identify clinically meaningful CSA phenotypes based on metabolic and inflammatory profiles and to determine phenotype-specific determinants of coronary spasm and endothelial dysfunction. METHODS:We analyzed 568 patients with suspected CSA and no obstructive coronary artery disease from the FUJI-SPASM (Feature-based Understanding of Joint Investigation for coronary Spasm Phenotypes and Associated Stratified Mechanisms) registry. Coronary spasm was assessed using intracoronary acetylcholine provocation testing. Unsupervised k-means clustering was performed using 20 standardized clinical and biochemical variables. Phenotype-specific determinants of spasm were identified using adaptive least absolute shrinkage and selection operator regression followed by multivariable logistic regression within each cluster. Endothelial function was assessed by flow-mediated dilation in a subset of 159 patients. RESULTS:Two phenotypes were identified. Cluster 0 (n = 231) showed metabolically dominant profiles with atherogenic dyslipidemia and insulin resistance, whereas cluster 1 (n = 337) showed inflammation-dominant profiles with preserved lipid levels but elevated high-sensitivity C-reactive protein (hs-CRP). Lower high-density lipoprotein cholesterol (HDL-C) was associated with coronary spasm in both clusters, while higher hs-CRP was independently associated with spasm only in the inflammation-dominant cluster. An HDL-C/hs-CRP-based stratification demonstrated a graded increase in spasm prevalence and worsening endothelial function. CONCLUSIONS:CSA comprises distinct metabolic and inflammatory phenotypes with differing determinants of coronary spasm and endothelial dysfunction. Reduced HDL-C represents a shared vulnerability across phenotypes, while inflammation confers additional risk. HDL-C/hs-CRP-based stratification provides a clinically accessible framework for individualized CSA risk assessment.

Background:Radiation-induced cardiovascular disease may appear decades after cancer therapy and can involve multiple vascular, valvular, myocardial, and conduction structures of the heart. Management is particularly challenging when prior irradiation results in a hostile chest environment and impaired wound healing. Case summary:A 31-year-old woman with a history of childhood right forearm rhabdomyosarcoma treated with resection, chemotherapy, and radiotherapy presented with recurrent syncope. Computed tomography angiography revealed asymmetric growth of the right-sided arteries, leading to a transient ischaemic attack. Further cardiovascular evaluation revealed multiple concomitant cardiovascular disorders, including valvular heart disease, high-grade atrioventricular block, bradycardia, and heart failure. Permanent pacemaker implantation and right-to-left axillary artery bypass prevented further syncopal episodes; however, heart failure continued to worsen. Two years later, she was hospitalized with severe heart failure and dyspnoea, and echocardiography revealed aortomitral continuity calcification and elevated filling pressure. She subsequently underwent the Bentall procedure, tricuspid valve replacement, and coronary artery bypass grafting for advanced coronary stenosis. However, her postoperative course was complicated by pleural effusion and haemoptysis, and she eventually died of multiorgan dysfunction. Discussion:This case illustrates the late cardiovascular effects of radiation therapy. Radiation-induced endothelial injury, fibrosis, and maladaptive wound-healing responses may contribute to delayed cardiovascular damage and poor postoperative recovery. In such patients, surgical decision-making should be multidisciplinary, and long-term follow-up is essential.

Lipoprotein(a) [Lp(a)] and vascular calcification have each been associated with poor outcomes in lower extremity arterial disease (LEAD). This study investigated whether elevated Lp(a) levels and severe calcification have combined prognostic value for major adverse limb events (MALE) after endovascular therapy (EVT). We retrospectively analyzed 145 patients who underwent EVT. Patients were classified according to the number of Lp(a)/ Peripheral Arterial Calcium Scoring System (PACSS) risk markers: elevated Lp(a) (≥ 30 mg/dL) and PACSS grade 4. The primary endpoint was 1-year MALE incidence. MALE occurred in 17 patients during follow-up. Patients were classified into three groups according to the number of Lp(a)/PACSS risk markers. The cumulative incidence of MALE differed significantly among the three groups (overall P = 0.032). Compared with the 0 risk-marker group, the 1 risk-marker group and the 2 risk-marker group had significantly higher risks of MALE (hazard ratio [HR], 3.175; 95

BACKGROUND:Arterial stiffness is a contributor to cardiovascular morbidity, but its role in elevated left ventricular (LV) filling pressure and heart failure with preserved ejection fraction (HFpEF) remains incompletely understood. OBJECTIVES:This study aimed to evaluate the relationship between arterial stiffness and the ratio of early diastolic transmitral flow velocity (E) to early diastolic mitral annulus velocity (e'), as well as its association with LV diastolic dysfunction. METHODS:This study cross-sectionally analyzed 335 patients with cardiovascular disease and an ejection fraction ≥50% who underwent the Cardio-Ankle Vascular Index (CAVI) measurement. Multivariable logistic regression was used to identify independent associated factors of elevated LV filling pressure, defined as E/e' >14. Smoothing spline analysis was used to assess the dose-response relationship between CAVI, age, and elevated E/e'. Mediation analysis was used to assess the direct and indirect effects of CAVI, age, and hypertension on elevated filling pressure. RESULTS:CAVI was independently associated with E/e' >14 (odds ratio (OR) 1.43; 95% confidence interval (CI): 1.17-1.74, p< 0.001) and diastolic dysfunction (OR 1.25; 95% CI 1.03-1.52, p = 0.024). CAVI enhanced risk stratification for elevated filling pressure (net reclassification index = 0.588, p < 0.001; integrated discrimination improvement = 0.035, p= 0.008). Smoothing spline analysis revealed a near-exponential increase in E/e' >14 risk above a CAVI threshold of 9.275. Mediated analysis indicated that CAVI accounted for 18.7% of the effect of age on elevated E/e' (p = 0.006). CONCLUSION:Arterial stiffness, as quantified by CAVI, independently increases the LV filling pressure and mediates age-related effects.

Introduction: Fatty liver is recognized as a risk factor for cardiovascular disease, and its severity can be assessed using the fatty liver index (FLI), a non-invasive marker calculated from body mass index, waist circumference, triglyceride, and gamma-glutamyl transferase levels. Despite its clinical utility, the association between FLI and long-term outcomes after percutaneous coronary intervention (PCI) remains unclear. Research Question: This study aimed to investigate whether FLI is associated with adverse clinical events, including all-cause death and repeat revascularization (RR), in patients undergoing PCI. Methods: We analyzed data from 576 patients who underwent PCI at a single center, enrolled in a prospective cohort registry. Patients were divided into four groups according to FLI quartiles (Q1–Q4). The primary endpoint was the 5-year cumulative incidence of all-cause death and repeat revascularization (RR), including myocardial infarction and ischemia-driven revascularization. Results: During the 5-year follow-up, 48 patients died (8.3%), and 58 experienced RR (10%). The incidence of all-cause death was significantly higher in Q1 (15%) compared with Q2 (7.7%), Q3 (7.0%), and Q4 (3.5%) (log-rank p=0.04, 0.03, and <0.01, respectively) (Figure 1). Multivariate Cox regression analysis showed that a higher FLI was associated with a lower risk of all-cause death (adjusted hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.97–0.99; p=0.03). In contrast, the incidence of RR was significantly higher in Q4 (19.7%) than in Q1 (3.6%), Q2 (7.3%), and Q3 (10.8%) (log-rank p<0.01, <0.01, and =0.04, respectively) (Figure 2). Multivariate analysis showed that a higher FLI was associated with a higher risk of RR (adjusted HR, 1.02; 95% CI, 1.01–1.03; p<0.01). Conclusions: A low FLI was associated with higher all-cause mortality, while a high FLI was associated with increased risk of repeat revascularization. These findings suggest that FLI reflects different aspects of clinical risk after PCI, and its assessment may be useful for predicting long-term outcomes in this population.

BACKGROUND:Drug-coated balloons (DCBs) are increasingly being used to treat superficial femoral artery (SFA) lesions during endovascular therapy (EVT). However, the evaluation of paclitaxel distribution following DCB treatment remains challenging. This study aimed to develop a novel criterion to systematically semi-quantitatively grade the degree of paclitaxel distribution using nonobstructive general angioscopy and analyze the clinical factors affecting this criterion. METHOD AND RESULTS:This study included 18 patients (20 limbs) who underwent EVT for SFA lesions using DCBs. Angioscopic observation of the vessel surface was performed before and after DCB treatment. The amount of paclitaxel distribution was systematically graded using the novel surface observation by nonobstructive general angioscopy of wall drug-distribution (SNOW) grade. Clinical factors were statistically analyzed to determine their relationship with the SNOW grade. Paclitaxel particles were observed on vessel walls after DCB treatment in all patients. A significant relationship was found between the DCB diameter and reference vessel and lumen diameter, measured by intravascular ultrasound; specifically, a same DCB-to-vessel ratio was associated with greater drug distribution. CONCLUSIONS:The SNOW grading system was successfully developed for systematic evaluation of paclitaxel distribution. Our findings suggest that appropriate DCB sizing is essential for adequate drug application, highlighting that an undersized DCB may provide insufficient coverage. Therefore, a careful DCB selection that balances optimal drug delivery with the imperative to avoid vessel injury is crucial.

BACKGROUND:Reduced insulin secretion is linked to diabetes and cardiovascular disease (CVD), but its role in non-diabetic CVD patients is unclear. The homeostasis model assessment of β-cell function (HOMA-β) measures pancreatic β-cell function. This study investigated the association between HOMA-β and adverse cardiovascular events in non-diabetic CVD patients. METHODS AND RESULTS:This study included 1301 non-diabetic CVD patients who underwent cardiac catheterization at the University of Yamanashi Hospital. HOMA-β was calculated based on fasting blood glucose and insulin levels. Patients were followed for 3 years to track adverse events, such as all-cause death, myocardial infarction, angina pectoris requiring percutaneous coronary intervention, and heart failure. Receiver operating characteristic curve analysis established a HOMA-β cut-off value of ≤49.3%. Kaplan-Meier analysis indicated that patients with HOMA-β ≤49.3% had a significantly higher risk of adverse events (P <0.001), with a 2.65-fold increased risk (hazard ratio 2.65; 95% confidence interval 1.97-3.57). Adding HOMA-β to traditional risk factors such as age, sex, estimated glomerular filtration rate, and left ventricular ejection fraction significantly improved risk prediction, as demonstrated by net reclassification improvement and integrated discrimination improvement. CONCLUSIONS:Decreased HOMA-β is a significant predictor of adverse cardiovascular events in CVD patients without diabetes. These findings suggest reduced insulin secretion contributes to worse outcomes, underscoring the importance of monitoring HOMA-β in this population.

Improved renal function (IRF) observed in acute heart failure (AHF) is associated with poor prognosis. Since IRF is linked to renal congestion resulting from inadequate decongestion, predicting IRF could enhance management strategies. The Fibrosis-4 (Fib-4) index, originally developed as a marker for liver fibrosis, correlates with hepatic congestion, which is associated with renal congestion, making it a potential predictor of IRF. This study aims to investigate whether the Fib-4 index can predict IRF in patients with AHF and preserved ejection fraction (AHFpEF). We analyzed 389 patients hospitalized for AHF between April 2004 and March 2022 at Yamanashi University Hospital. All-cause mortality was monitored for 1 year. IRF was defined as a ≥ 20

Background: Transcatheter aortic valve replacement (TAVR) has broadened treatment options for elderly patients with severe aortic valve stenosis (AVS), including those with challenging vascular anatomy such as increased aortic tortuosity. We previously demonstrated that a higher aortic tortuosity index (ATI), defined as the ratio of aortic length (from the sinotubular junction to the terminal aorta) to body height measured by 3D-computed tomography, was associated with complete atrioventricular block (CAVB). However, the anatomical mechanisms linking ATI to conduction disturbances (CD) requiring pacemaker implantation (PMI) remain unclear. Purpose: To investigate whether anatomical variations—specifically, aortic angle and membranous septum (MS) length—mediate the association between ATI and CD requiring PMI after TAVR. Methods: We analyzed 198 consecutive patients with severe AVS who underwent TAVR. ATI, aortic angle, and MS length were quantified using pre-procedural 3D-CT imaging. CD requiring PMI within 30 days post-TAVR was observed in 20 patients (10.2%). Patients were stratified by median ATI (3.24), aortic angle (49°), and MS length (3.3 mm). Structural equation modeling (SEM) was applied to evaluate both direct and indirect effects of ATI on CD through aortic angle and MS length. Results: Patients with higher ATI (>3.24) had a significantly greater incidence of CD requiring PMI than those with lower ATI (18.2% vs. 3.0%, p = 0.001). SEM demonstrated a significant direct effect of higher ATI on CD (path coefficient = 0.26, p < 0.01), along with a significant indirect effect mediated by aortic angle and MS length (path coefficient = 0.15, p < 0.05). Conclusion: Higher ATI is associated with increased risk of CD requiring PMI after TAVR, and this relationship is mediated by steeper aortic angle and shorter MS length. Aortic tortuosity may reflect age-related anatomical remodeling that predisposes patients to conduction injury during TAVR.

The prognosis of patients with aortic aneurysm (AA) and cardiovascular comorbidities remains suboptimal compared to that of the general population, highlighting the need for reliable mortality biomarkers. Apolipoprotein A2 (ApoA2) is a structural and functional component of high-density lipoprotein cholesterol (HDL-C), but its relevance to all-cause mortality remains unclear. Therefore, we investigated the prognostic value of ApoA2 in patients with AA after surgical repair. ApoA2 levels were measured in 203 consecutive patients with AA who were successfully treated with surgical repair. The primary focus was the predictive value of ApoA2 levels for mortality events. During a median follow-up of 3.5 years, mortality events were observed in 32 patients (15.8 %). Patients with mortality events had lower ApoA2 levels than the survivors [22.0 (19.0, 25.0) mg/dL versus 25.0 (22.0, 29.0) mg/dL, P < 0.001]. ApoA2 was inversely correlated with age, BNP, C-reactive protein (CRP), and fibrinogen levels and positively correlated with eGFR. Multivariate Cox analysis identified ApoA2 (HR 0.92, 95% CI 0.86-0.99), eGFR < 60 mL/minute/1.73 m(2) (HR 3.49, 95% CI 1.49-8.20), COPD (HR 2.63, 95% CI, 1.07-6.49), and thoracic AA (HR 2.54, 95% CI 1.25-5.18) as independent mortality predictors. Moreover, the addition of ApoA2 levels significantly improved the discriminative ability of the baseline risk factors in predicting mortality (AUC 0.79 versus 0.73, P = 0.04). Therefore, ApoA2 is a potential biomarker for predicting long-term mortality in patients with AA following surgical repair, and may contribute to improved risk stratification in this high-risk population.

Aim: The prognosis of patients with aortic aneurysm (AA) and cardiovascular comorbidities remains suboptimal compared with that of the general population, highlighting the need for reliable mortality biomarkers. Apolipoprotein A2 (ApoA2) is a structural and functional component of high-density lipoprotein cholesterol (HDL-C). However, cardioprotective effects of ApoA2 still remain controversial. Therefore, we investigated the prognostic value of ApoA2 in patients with AA after surgical repair. Methods: ApoA2 levels were measured in 203 consecutive patients with AA who were successfully treated with surgical repair. The primary focus was the predictive value of ApoA2 levels for mortality events. Results: During a median follow-up of 3.5 years, mortality events were observed in 32 patients (15.8 %). Patients with mortality events had lower ApoA2 levels than survivors [22.0 (19.0, 25.0) mg/dL vs. 25.0 (22.0, 29.0) mg/dL, p<0.001]. ApoA2 was inversely correlated with age, BNP, C-reactive protein (CRP), and fibrinogen levels and positively correlated with eGFR. Multivariate Cox analysis identified ApoA2 (HR 0.92, 95% CI 0.86–0.99), eGFR <60 ml/min/1.73 m2 (HR 3.49, 95% CI 1.49–8.20), COPD (HR 2.63, 95% CI 1.07–6.49), and thoracic AA (HR 2.54, 95% CI 1.25–5.18) as independent mortality predictors. Moreover, the addition of ApoA2 levels significantly improved the discriminative ability of baseline risk factors in predicting mortality (AUC 0.79 vs. 0.73, p=0.04). Conclusions: ApoA2 is a potential biomarker for mortality risk stratification in patients with AA after surgical repair, with possible therapeutic implications for improving the outcomes in AA.

The psoas muscle area (PMA) and rectus femoris muscle area (RFMA) have been used to estimate whole-body muscle mass in elderly patients. However, it is unclear whether combining these measurements can improve the predictive ability of traditional risk factors for adverse clinical events in elderly patients with aortic valve stenosis (AVS). We analyzed data from 153 patients with AVS who underwent transcatheter aortic valve replacement (TAVR), and measured PMA and RFMA using computed tomography (CT) before the procedure. This study assessed a composite of adverse clinical events including all-cause death and heart failure (HF) requiring hospitalization for up to 3 years after TAVR. During the follow-up period, 31 patients experienced adverse clinical events (19 died, and 12 had HF). The multivariate Cox hazards analysis demonstrated that patients exhibiting lower PMA (males with < 3.36 cm2/m2 and females with < 2.52 cm2) and lower RFMA (males with < 3.26 cm2/m2 and females with < 3.15 cm2/m2) had a higher probability of experiencing adverse clinical events compared to those with higher PMA and RFMA values, whether in combination or alone (P < 0.05). Additionally, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses showed that the combination of lower PMA and RFMA had a greater incremental effect on the predictive value of clinical risk factors for adverse clinical events. Therefore, the combined measurement of skeletal muscles using CT scans may be a valuable tool for assessing the risk of AVS in elderly patients undergoing TAVR.

Background: Non-ST-elevation myocardial infarction (NSTEMI) carries a poor prognosis, and accurately prognostication has significant clinical importance. In this study, we analyzed the predictive value of the CHADS2, 2 , CHA2DS2-VASc, 2 DS 2-VASc, and R2-CHADS2 2-CHADS 2 scores for major adverse cardiac events (MACE) following percutaneous coronary intervention (PCI) in patients with NSTEMI using data from a prospective multicenter registry. Methods and Results: The registry included 440 consecutive patients with NSTEMI and coronary artery disease who underwent successful PCI. Patients were clinically followed for up to 3 years or until the occurrence of MACE. MACE was defined as a composite of all-cause death and nonfatal MI. During the follow-up period, 55 patients (12.5%) experienced MACE. Risk analysis of MACE occurrence, adjusted for the multivariable model, demonstrated a significant increase in risk with higher CHADS2, 2 , CHA2DS2- 2 DS 2- VASc, and R2-CHADS2 2-CHADS 2 scores. Kaplan-Meier analysis showed a higher incidence of MACE in patients with higher CHADS2, 2 , CHA2DS2-VASc, 2 DS 2-VASc, and R2-CHADS2 2-CHADS 2 scores, both in the short- and long-term periods. Conclusions: Patients with NSTEMI and higher CHADS2, 2 , CHA2DS2-VASc, 2 DS 2-VASc, and R2-CHADS2 2-CHADS 2 scores displayed a greater incidence of MACE.

Background and Aim: Persistent coronary endothelial vasomotor dysfunction predicts future coronary events; however, performing multiple invasive endothelial function tests is difficult in actual clinical practice. This study examined whether carotid plaque changes can predict persistent coronary endothelial dysfunction using serial assessments of the coronary vasomotor response to acetylcholine (ACh) in the infarct-related artery (IRA) among patients with ST-elevation acute myocardial infarction (STEMI). Methods: This study included 169 consecutive patients with a first acute STEMI due to the left anterior descending coronary artery (LAD) occlusion who underwent successful reperfusion therapy with percutaneous coronary intervention. The vasomotor response to ACh in the LAD was measured within two weeks of acute myocardial infarction (AMI) (first test) and repeated at six months (second test) after AMI under optimal anti-atherosclerotic therapy. Ultrasonography of the bilateral common carotid artery (CCA) and internal carotid artery (ICA) was performed during the acute phase, and the thickest intima media thickness (IMT) of either artery was measured as the maximum IMT. After six months, the IMT at the site of maximal IMT was measured to determine whether there was an increase or decrease in IMT. Results: Finally, 87 STEMI patients analyzed in this study. At 6 months, 25 patients (28.7%) showed carotid plaque progression. In a multivariable adjusted analysis, carotid plaque progression was identified as an independent predictor of persistent coronary endothelial dysfunction, both in terms of coronary diameter response [OR 3.22, 95% confidence interval1.13 - 9.15, P = 0.03] and coronary flow response [OR 2.65, 95% confidence interval 1.01 - 7.00, P = 0.04]. Conclusions: Carotid plaque progression could independently predict persistent endothelial vasomotor dysfunction in the IRA of STEMI survivors.

Although guidelines recommend early aspirin administration after diagnosis of ST-elevation myocardial infarction (STEMI), the decision of pretransfer aspirin administration is at the discretion of the primary physicians. Therefore, this study aimed to determine whether pretransfer aspirin administration was associated with better angiographical outcomes in patients with STEMI. This study compared the angiographic findings of thrombolysis in myocardial infarction (TIMI) flow grade in the infarct-related artery before percutaneous coronary intervention (PCI) between patients who received pretransfer aspirin and those who did not. In total, 28 patients (11.2%) were administered aspirin before transfer and 219 (88.8%) were administered aspirin upon arrival at the hospital. Propensity score matching yielded 135 patients [27 patients (20%) who were administered aspirin before transfer and 108 patients (80%) who were administered aspirin upon arrival at the hospital]. Patients who received pretransfer aspirin had a higher rate of TIMI-3 flow before PCI compared to those who did not receive pretransfer aspirin [8 (28.6%) versus 15 (6.8%), P < 0.01, in all study patients; 8 (26.6%) versus 7 (6.5%), P < 0.01, in propensity-score-matched patients]. Multivariable logistic regression analysis revealed that pretransfer aspirin administration was significantly associated with the presence of TIMI-3 flow before PCI, independent of age, gender, transfer time, and statin use (OR: 5.43, 95% CI: 1.94-15.2, P < 0.01, in all study patients; OR: 6.17, 95% CI: 1.86-20.46, P < 0.01, in propensity-score-matched patients). Pretransfer aspirin administration could lead to the early restoration of coronary blood flow in patients with STEMI, supporting its active use in STEMI care.