Ishibashi K, Oka S, Nakamura T
… +13 more, Miyazaki Y, Wakamiya A, Ueda N, Nakajima K, Kamakura T, Wada M, Inoue Y, Miyamoto K, Nagase S, Aiba T, Kusano K, Aonuma K, HINODE Investigators
BACKGROUND: The usefulness of non-sustained ventricular tachycardia (NSVT) in predicting sudden cardiac death is not clear. The Heart Failure Indication and Sudden Cardiac Death Prevention Trial Japan (HINODE) investigat...BACKGROUND: The usefulness of non-sustained ventricular tachycardia (NSVT) in predicting sudden cardiac death is not clear. The Heart Failure Indication and Sudden Cardiac Death Prevention Trial Japan (HINODE) investigated the effectiveness of implantable cardioverter defibrillator (ICD) treatment for primary prevention in Japanese patients. This subanalysis examined associations between NSVT and clinical outcomes. METHODS AND RESULTS: Patients with ICD/cardiac resynchronization therapy defibrillator (CRT-D) for primary prevention (n=164) were divided into NSVT (n=25) and no NSVT (n=139) groups. NSVT was defined as ventricular tachycardia of <30 s duration regardless of pulse rate. The median follow-up period was 19 months, mean patient age was 67 years, and 21% of patients were female. There were no significant differences between the 2 groups in the frequency ischemic cardiomyopathy, mean left ventricular ejection fraction, or (in Kaplan-Meier analysis) in all-cause mortality (log-rank P=0.613), ventricular arrhythmia (VA; log-rank P=0.282), or the composite endpoint of all-cause death and VA events (log-rank P=0.352). Cox proportional hazards analysis indicated that NSVT was not a prognostic factor. CONCLUSIONS: Prognosis was similar between the NSVT and no NSVT groups. NSVT, although recommended in guidelines for risk stratification, was not associated with appropriate ICD therapy in patients with ICD/CRT-D for primary prevention. The utility of NSVT in guiding ICD indication may depend on its definition and the characteristics of the studied population, and requires further investigation.
BACKGROUND: Atriogenic tethering (AT) is a characteristic feature of the mitral valve in atrial functional mitral regurgitation (AFMR). However, the factors associated with AT are not well known. METHODS AND RESULTS: Thi...BACKGROUND: Atriogenic tethering (AT) is a characteristic feature of the mitral valve in atrial functional mitral regurgitation (AFMR). However, the factors associated with AT are not well known. METHODS AND RESULTS: This was a post hoc analysis of REVEAL-AFMR, a retrospective observational study involving patients with moderate or greater AFMR. A stepwise binary logistic regression model was used to identify factors associated with AT. The primary endpoint was a composite of cardiovascular death, heart failure hospitalization, and mitral valve intervention. Of 1,007 patients, 245 (24%) had AT and 762 (76%) did not. Of 15 clinical variables related to AT in AFMR, greater left ventricular end-systolic dimension and left atrial diameter were independently associated with AT. The 3-year rate of freedom from the primary outcome was significantly lower in the group with than without AT (63.2% vs. 71.2%; P=0.002). The risk of the primary outcome was significantly higher in the group with than without AT (adjusted hazard ratio 1.34; 95% confidence interval 1.04-1.74; P=0.026), although the results were inconsistent in the sensitivity analysis using propensity score overlap weighting. CONCLUSIONS: AT was identified in 24% of patients with moderate or greater AFMR. Greater left ventricular end-systolic and left atrial anteroposterior dimensions were factors associated with AT. Among patients with AFMR, those with AT showed a poor prognosis.
BACKGROUND: Passive leg lifting (PLL) may serve as a simple alternative to simulate exercise stress. METHODS AND RESULTS: We evaluated 33 patients with PH who underwent PLL-RHC and exercise right heart catheterization (R...BACKGROUND: Passive leg lifting (PLL) may serve as a simple alternative to simulate exercise stress. METHODS AND RESULTS: We evaluated 33 patients with PH who underwent PLL-RHC and exercise right heart catheterization (RHC); 25 patients were classified as having PLL-induced PH (LIPH), demonstrating significant increases in mean pulmonary arterial pressure (mPAP) and mPAP-cardiac output slopes. Strong correlations were observed between PLL-RHC and exercise RHC measurements. CONCLUSIONS: PLL-RHC may represent a simple method for detecting EIPH.
BACKGROUND: The diagnostic utility of the exercise electrocardiogram (ECG) in detecting coronary microvascular dysfunction (CMD) remains unclear. METHODS AND RESULTS: We analyzed 101 patients without obstructive coronary...BACKGROUND: The diagnostic utility of the exercise electrocardiogram (ECG) in detecting coronary microvascular dysfunction (CMD) remains unclear. METHODS AND RESULTS: We analyzed 101 patients without obstructive coronary artery disease (CAD) who underwent the Master double 2-step exercise ECG and invasive coronary physiological assessment. The sensitivity, specificity, positive predictive value, and negative predictive value of ischemic ECG changes for detecting CMD were 0.44, 0.97, 0.85, and 0.84, respectively. The post-test probability of CMD increased from 24.8% to 82.8% with a positive ECG finding. CONCLUSIONS: The Master double 2-step exercise ECG demonstrated high specificity for detecting CMD in patients without obstructive CAD.
BACKGROUND: Coronary microvascular dysfunction (CMD) is characterized by impaired myocardial flow reserve (MFR) in patients with non-obstructive coronary artery disease (CAD). The real-world incidence of CMD, risk factor...BACKGROUND: Coronary microvascular dysfunction (CMD) is characterized by impaired myocardial flow reserve (MFR) in patients with non-obstructive coronary artery disease (CAD). The real-world incidence of CMD, risk factors for decreased MFR, and characteristics of the two CMD endotypes (classical and endogenous) in this population remain unclear. METHODS AND RESULTS: After screening 1,313 patients with suspected or known CAD who underwent N-ammonia positron emission tomography (PET), 345 with non-obstructive CAD were retrospectively enrolled in the study. Stress/resting myocardial blood flow (MBF) was quantified using N-ammonia PET. PET-assessed CMD (impaired MFR <2.0) was diagnosed in 60 (17%) patients. Independent predictors of decreased MFR included older age, female sex, anemia, and hypertension; however, these factors accounted for only 32% of the observed variability in MFR. Symptomatic status was not an independent predictor of decreased MFR. Patients with classical CMD (resting MBF <1.3 mL/min/g) had higher summed stress scores and stress/resting coronary vascular resistance, whereas patients with endogenous CMD (resting MBF ≥1.3 mL/min/g) showed female dominance, higher stress MBF, and a higher resting rate-pressure product. CONCLUSIONS: Among patients with non-obstructive CAD, approximately 1 in 5 had PET-assessed CMD. Age, female sex, anemia, and hypertension were independent clinical factors associated with impaired MFR, which explained a limited portion of its variability. Further examination of unidentified or unmeasured factors is warranted.
BACKGROUND: Right ventricular endomyocardial biopsy may cause conduction disturbances, particularly complete right bundle branch block (CRBBB); however, the impact of using the venous access site remains unclear. METHODS...BACKGROUND: Right ventricular endomyocardial biopsy may cause conduction disturbances, particularly complete right bundle branch block (CRBBB); however, the impact of using the venous access site remains unclear. METHODS AND RESULTS: In 274 patients, CRBBB occurred more frequently with the transfemoral than with the transjugular approach (29.2% vs. 6.7%, P<0.001). The transjugular approach independently reduced CRBBB risk (odds ratio 0.17, P<0.001). Sustained CRBBB was also less frequent (8.3% vs. 1.1%, P=0.007). Major complications, including stroke, pacemaker implantation, and death, were absent. CONCLUSIONS: The transjugular approach reduces CRBBB risk and is a safer option for patients at risk of complete atrioventricular block.
Minami Y, Ikari Y, Harada M
… +12 more, Suzuki H, Fukui K, Ako J, Akashi YJ, Hibi K, Kamioka N, Koga M, Tashiro K, Gohbara M, Onoue K, Saito Y, Komuro I
The management of low-density lipoprotein cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease, particularly those with acute coronary syndrome (ACS), has evolved significantly. Recent evidence emp...The management of low-density lipoprotein cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease, particularly those with acute coronary syndrome (ACS), has evolved significantly. Recent evidence emphasizes the importance of early and intensive LDL-C lowering for reducing recurrent cardiovascular events by stabilizing vulnerable plaques. Global guidelines now advocate for more aggressive LDL-C targets, with a common recommendation of <55 mg/dL for high-risk ACS patients. However, regional variations persist in specific target levels, pharmacologic strategies, and follow-up schedules due to differences in healthcare infrastructure, epidemiology, and risk assessment frameworks. Despite guideline updates, achieving recommended LDL-C levels in real-world practice remains challenging, primarily due to issues like healthcare system limitations, patient adherence, and clinical inertia. Some regions in Japan have established local clinical pathways that demonstrate improvements in attainment of LDL-C targets and clinical outcomes. This article explores the current global LDL-C targets and treatment strategies for ACS patients, aiming to enhance the achievement of optimal LDL-C levels and reduce subsequent adverse events.
BACKGROUND: This study evaluated early and mid-term clinical outcomes of surgical correction for anomalous aortic origin of a coronary artery (AAOCA) and expansion of surgical indications beyond current guidelines, parti...BACKGROUND: This study evaluated early and mid-term clinical outcomes of surgical correction for anomalous aortic origin of a coronary artery (AAOCA) and expansion of surgical indications beyond current guidelines, particularly for asymptomatic patients with anomalous aortic origin of the right coronary artery (AAORCA). METHODS AND RESULTS: Between December 2004 and July 2023, 34 patients underwent surgery for AAOCA. Surgical indications included evidence of myocardial ischemia and high-risk anatomy. AAOCA was assessed pre- and postoperatively using imaging and functional studies. Early and mid-term outcomes were evaluated retrospectively. AAORCA was the predominant type (n=32; 94.1%), and 32 of 34 patients (94.1%) underwent unroofing. Five (14.7%) asymptomatic AAORCA patients had a history of Kawasaki disease. There were no surgical mortalities or coronary artery-related complications. Of 12 patients with symptoms or signs likely related to the coronary artery in the early postoperative period, 2 had persistent symptoms until the last follow-up. During follow-up, 2 patients had suspicious mild coronary stenosis on computed tomography, and 1 had decreased stress perfusion on a myocardial perfusion scan. Among patients with preoperative abnormalities, 92.3% exhibited postoperative functional improvement. CONCLUSIONS: Surgical treatment of AAOCA, primarily through unroofing, is safe and effective, with favorable early and mid-term outcomes. Our findings support consideration of surgery for asymptomatic AAORCA patients with high-risk anatomy due to the potential risk of sudden cardiac events and the substantial benefits of the procedure.
BACKGROUND: We evaluated the surgical outcomes of modified right ventricle (RV) overhaul (mRVOh), implemented as part of comprehensive management for pulmonary atresia with intact ventricular septum (PA-IVS). METHODS AND...BACKGROUND: We evaluated the surgical outcomes of modified right ventricle (RV) overhaul (mRVOh), implemented as part of comprehensive management for pulmonary atresia with intact ventricular septum (PA-IVS). METHODS AND RESULTS: Twenty-five mRVOh procedures were performed in 23 patients with PA-IVS without RV-dependent coronary circulation. The procedure involved RV sinus myectomy, infundibular muscle resection, and tricuspid valve (TV) and pulmonary valve (PV) repair. In addition, in neonates and young infants, Blalock-Taussig shunt or patent ductus arteriosus banding was performed simultaneously. TV and PV annulus sizes were measured using echocardiography; RV function and volume were assessed using magnetic resonance imaging (MRI) in 18 patients. The median age and body weight at the time of mRVOh were 7.0 months and 7.1 kg, respectively. Biventricular repair was performed in 19 patients, and 6 required reoperations, including 2 with redo mRVOh. After mRVOh, the mean TV and PV annulus z-scores showed a significant increase towards the normal range, from -1.91 to -1.40 (P=0.031), and from -2.23 to -1.11 (P=0.014), respectively. Serial postoperative MRI showed significant increases in RV end-diastolic and end-systolic volume indices, stroke volume index, and cardiac index (P<0.001 for all), with preserved RV function. CONCLUSIONS: Both RV size and TV annulus showed proportionate growth after mRVOh. mRVOh may be a viable option for facilitating sustainable RV and TV growth in selected patients with PA-IVS.
Miyashita K, Muramatsu T, Revaiah PC
… +20 more, Nakazawa G, Ishibashi Y, Kozuma K, Asano T, Katagiri Y, Okamura T, Morino Y, Kogame N, Ono M, Miyazaki Y, Nakatani S, Nakamura M, Tobe A, Oshima A, Ying-Tsai T, Garg S, Tanabe K, Ozaki Y, Serruys PW, Onuma Y
BACKGROUND: In the presence of a potent P2Yinhibitor such as prasugrel, the additional clinical antithrombotic benefit of aspirin is unclear. The feasibility of prasugrel monotherapy without aspirin after percutaneous co...BACKGROUND: In the presence of a potent P2Yinhibitor such as prasugrel, the additional clinical antithrombotic benefit of aspirin is unclear. The feasibility of prasugrel monotherapy without aspirin after percutaneous coronary intervention (PCI) has been demonstrated in chronic coronary syndrome, but is yet to be assessed in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) and low anatomical complexity. METHODS AND RESULTS: ASET-Japan is a single-arm study investigating the safety of prasugrel 12-month monotherapy with a locally approved dose (loading 20 mg; maintenance 3.75 mg), started immediately after successful PCI using platinum-chromium everolimus-eluting SYNERGY stents. The primary ischemic endpoint is a composite of cardiac death, spontaneous target vessel myocardial infarction, or definite stent thrombosis; the primary bleeding endpoint is Bleeding Academic Research Consortium (BARC) Type 3 and 5 bleeding. ASET-Japan recruited 101 NSTE-ACS patients from 11 Japanese sites. The mean (±SD) age was 69.1±12.3 years and 36.6% had a PRECISE-DAPT score >25. The mean anatomical SYNTAX score was 7.9±4.7. At 1 year, the primary ischemic endpoint occurred in 1 patient (1.0%; cardiac death). Two BARC Type 3a bleeding events occurred (2.0%): 1 due to a gastric ulcer and 1 to a descending colon malignancy. CONCLUSIONS: Low-dose (3.75 mg/day) prasugrel monotherapy started immediately after SYNERGY stent deployment was feasible and safe in selected NSTE-ACS patients.
Okuma Y, Yoshie K, Suzuki S
… +12 more, Minamisawa M, Nishikawa K, Kanai M, Kimura K, Ueki Y, Oguchi Y, Kato T, Saigusa T, Ebisawa S, Okada A, Motoki H, Kuwahara K
BACKGROUND: With an increase in the aging population, heart failure (HF) has become a major healthcare problem. Therefore, early detection of key signals characteristic of each of the stages of HF has the potential to im...BACKGROUND: With an increase in the aging population, heart failure (HF) has become a major healthcare problem. Therefore, early detection of key signals characteristic of each of the stages of HF has the potential to improve treatment and palliative care. Metabolomics profiling may be useful in identifying biomarkers of HF and improving HF treatment. METHODS AND RESULTS: This study was a retrospective subanalysis of the CURE-HF registry, a prospective observational study of patients with acute decompensated HF. Patients were divided into 3 groups: those who died within 3 months of discharge due to cardiovascular disease (CVD), those who died within 3-6 months of discharge due to CVD, and those who survived >2 years as a control group. Serum samples from 28 patients (median age 85 years [interquartile range 74-90 years]; 11 (39.3%) women) were subjected to capillary electrophoresis time-of-flight mass spectrometry. Partial least-squares (PLS) discriminant analysis showed a negative correlation between carnitine and short-term mortality (R=-0.508, P=0.006). Urea (R=-0.597, P<0.001) and symmetric dimethylarginine (R=-0.634, P<0.001) were negatively correlated with survival, while tryptophan was positively correlated with survival (R=0.548, P=0.003). CONCLUSIONS: Carnitine, symmetric dimethylarginine, urea, and tryptophan appear to be critical biomarkers for monitoring terminal stages in HF. Our results suggest that myocardial energy metabolism and renal dysfunction are associated with changes in the metabolome.
Cancer is widely recognized as one of the major risk factors for thrombosis, and cancer-associated thrombosis (CAT) is a concept that also encompasses arterial and venous thromboembolism. The risk factors for CAT of clin...Cancer is widely recognized as one of the major risk factors for thrombosis, and cancer-associated thrombosis (CAT) is a concept that also encompasses arterial and venous thromboembolism. The risk factors for CAT of clinical concern are assumed to be a complex combination of patient-related factors, the cancer itself, factors related to anticancer therapy, tissue factors expressed on cancer cell membranes, and cytokines released by cancer cells to increase inflammation and coagulation at remote sites. In addition, some anticancer agents are known to damage vascular endothelial cells and cause thrombus formation; early diagnosis and treatment of CAT is recommended because CAT is a significant risk factor for poor prognosis in cancer patients.
BACKGROUND: In aging societies, shared tools are needed to assess and communicate activities of daily living (ADL). The Barthel Index (BI) is widely used in administrative data but remains underutilized in discharge plan...BACKGROUND: In aging societies, shared tools are needed to assess and communicate activities of daily living (ADL). The Barthel Index (BI) is widely used in administrative data but remains underutilized in discharge planning. METHODS AND RESULTS: We analyzed 605 older cardiovascular patients discharged from a regional hospital, classifying functional levels by BI ambulation, total score, and 6-minute walk distance. Higher levels corresponded with greater ADL independence across BI items. CONCLUSIONS: The BI reflects structured functional tiers and serves as a common language in care coordination.
BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease with a poor prognosis and no curative therapy. It may present as arrhythmogenic sudden cardiac death and inevitably progress to t...BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease with a poor prognosis and no curative therapy. It may present as arrhythmogenic sudden cardiac death and inevitably progress to terminal heart failure due to the loss of contractile tissue. This study aimed to generate knock-in (KI) mice carrying the 2 genetic variants (DSG2 p.R292C and p.D494A) most frequently found in Japanese ARVC patients, characterize their cardiac phenotype, and compare the results with those of human ARVC. METHODS AND RESULTS: Variants were introduced using CRISPR/Cas9 genome editing at the corresponding mouse locations: Dsg2 p.R297C (RC) and p.D499A (DA). Cardiac function, morphology, and electrophysiology were evaluated using echography, magnetic resonance imaging, and telemetry. Tissue and cardiomyocytes were examined histologically. All mice with the variants developed biventricular cardiac dysfunction after 8 weeks of age, and it progressed with age. There was a significant variability in phenotype expression. Mice with RC died suddenly at 9 weeks of age. Some homozygous RC mice showed arrhythmia and conduction abnormalities on telemetry. In both variants, staining of cardiac sections revealed significant fibrosis, and apoptosis was detected using the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay. CONCLUSIONS: We generated a KI ARVC mouse model with significant similarities to human disease. This model could be used for the elucidation of pathogenesis and the development of optimal therapy for ARVC.