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Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

Cabozantinib is a multikinase inhibitor that exerts anticancer activity against malignancies such as renal tumors and leukemia. Although other agents that belong to the same category can cause cardiotoxicity, there is a paucity of information on the safety profile of cabozantinib. Herein, we present the case of a 62-year-old woman who developed acute heart failure (HF) following the initiation of cabozantinib for a metastatic renal tumor. She had no history of cardiovascular disease. Echocardiography prior to chemotherapy revealed normal cardiac function. However, she developed sudden onset of dyspnea 23 days following cabozantinib initiation. The chest X-ray showed newly developed congestion and cardiomegaly, and echocardiography revealed severe impairment of systolic and diastolic function. She was referred to the intensive care unit for non-invasive positive pressure ventilation and infusion of inotropes. The cardiac function fairly recovered on day 46; thereafter, supportive therapy, followed by guideline-directed medical therapy for HF with reduced ejection fraction was provided. We describe the first case of severe acute HF following cabozantinib initiation without underlying heart disease. Clinicians should plan follow-up schedules and be cautious of the development of HF when they initiate the agent, even if patients appear to have a low cardiovascular disease risk. LEARNING OBJECTIVES: • We report the first case of acute heart failure following cabozantinib initiation without an underlying heart disease. • Prompt discontinuation of the agent and supportive therapy with guideline-directed medications can allow adequate recovery of cardiac function, even if the severity of heart failure is high. • Careful follow-up following the initiation is warranted when clinicians plan to initiate cabozantinib, even if patients appear to have low risk of cardiovascular disease.

ObjectiveSudden cardiac death (SCD) is the major cause of death in cardiac sarcoidosis (CS). We aimed to identify the prognostic markers for sustained ventricular tachycardia (sVT) and SCD in patients with CS.MethodsWe performed a prospective observational cohort study for patients with CS diagnosed according to the Japanese or Heart Rhythm Society guidelines between June 2008 and March 2020 in our hospital. The primary endpoint was a composite of the first sVT and SCD. The levels of urinary 8-hydroxy-2′-deoxyguanosine (U-8-OHdG), a marker of oxidative DNA damage that reflects the inflammatory activity of CS, other biomarkers, and indices of cardiac function and renal function were measured on admission.ResultsEighty-nine consecutive patients with CS were enrolled; 28 patients with no abnormal18F-fluorodeoxyglucose (18F-FDG) accumulation in the heart were excluded and 61 patients with abnormal18F-FDG accumulation were followed up for a median of 46 months (IQR: 20–84). During the follow-up period, 15 of 61 patients showed sVT (n=12) or SCD (n=3). A Cox proportional hazard model showed that U-8-OHdG concentration and presence of ventricular aneurysm (VA) were independent predictors of first sVT/SCD. The cut-off U-8-OHdG concentration for predicting first sVT/SCD was 14.9 ng/mg·Cr. Patients with U-8-OHdG concentration ≥14.9 ng/mg·Cr and VA showed a significantly increased risk of sVT/SCD.ConclusionsU-8-OHdG and presence of VA were powerful predictors of first sVT/SCD in patients with CS, facilitating the stratification of cardiac events and providing relevant information about the substrates of ventricular tachycardia.

After a percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD), in-stent neoatherosclerosis may pose a risk of in-stent restenosis (ISR). To clarify whether non-fasting hypertriglyceridemia contributes to ISR, we examined the relationship between non-fasting hypertriglyceridemia (i.e., triglyceride (TG) level ≥ 200 mg/dL) and ISR after stenting with a bare metal stent (BMS) post-primary PCI in patients with CAD by means of a single-site retrospective analysis. A total of 1,039 patients with CAD were enrolled, and 86 patients (112 lesions) were evaluated for BMS-ISR 3-6 months post-primary PCI. The percentage of patients with non-fasting hypertriglyceridemia was significantly higher in the ISR (+) group than in the ISR (-) group (P < 0.009). The follow-up period and number of patients in the ISR (+) group were significantly smaller than those in the ISR (-) group (P < 0.001). There were no significant between-group differences in the other baseline patient characteristics before the primary PCI or at the time of the follow-up coronary angiography. However, at the follow-up period, the ISR (+) group had significantly lower diastolic blood pressure and high-density lipoprotein cholesterol levels (P = 0.015) and significantly higher TG levels (P = 0.012) than the ISR (-) group. A multiple logistic regression analysis demonstrated that non-fasting hypertriglyceridemia and a follow-up period of ≥ 6 months were independent risk factors for ISR after primary PCI in patients with BMS implantation for stenotic CAD (P = 0.006), with an adjusted odds ratio of 8.232 (1.201-56.410) and 0.006 (95% confidence interval < 0.001-0.045), respectively. Non-fasting hypertriglyceridemia may be an additional independent risk factor for BMS-ISR after primary PCI in patients with CAD.

A beneficial surrogate marker for evaluating the effect of medical therapy is warranted to avoid deferred lesion revascularization. Similar to coronary artery imaging for monitoring the effects of medical therapy by analyzing plaque regression and stabilization, we hypothesized that evaluation of serial changes in the quantitative flow ratio (QFR) would serve as a surrogate marker of the effects of medical therapy against deferred lesion revascularization. Here, we investigated serial changes in QFR over time after percutaneous coronary intervention in patients who underwent medical therapy as a secondary prevention. Patients with intermediate stenosis in an untreated vessel observed at the baseline (BL) coronary angiography and follow-up (FU) coronary angiography performed 6–18 months after BL angiography were screened in 2 centers. A total of 52 patients were able to analyze both BL and FU QFR. The median QFR was 0.83 (IQR, 0.69, 0.89) at BL and 0.80 (IQR, 0.70, 0.86) at FU. The number of positive ΔQFR and negative ΔQFR were 21 and 31, respectively. The median ΔQFR was 0.05 (IQR, 0.03, 0.09) in positive ΔQFR and – 0.05 (IQR, – 0.07, – 0.03) in negative ΔQFR (p

Data regarding prognostic events following catheter ablation (CA) for atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) are scarce. We conducted this study to compare the incidence of major adverse clinical events (MACE) following CA for AF between patients with HFpEF and those with systolic heart failure (HF).This single-centre observational study included 142 patients with HF who underwent CA for AF (median follow-up: 4.0 [2.6, 6.3] years). The patients were grouped based on the presence of HFpEF (n = 84) and systolic HF (left ventricular ejection fraction50%, n = 58). We compared the cumulative incidence and incidence rate of MACE, comprising all-cause death, unplanned cardiovascular hospitalization (CVH), and HF hospitalization (HFH) between both groups and the number of HFH before and after CA in each group. Multivariate analysis was performed to identify the predictors of MACE in patients with HFpEF. The incidence of MACE was comparable between the groups (following the first procedure: HFpEF: 23%, 4.7/100 person-years, vs. systolic HF: 28%, 6.6/100 person-years, P = 0.18; last procedure: 20%, 4.8/100 person-years, vs. 24%, 6.9/100 person-years, P = 0.21). Although the incidence of HFH was lower in patients with HFpEF than in those with systolic HF (first procedure: 14%, 2.9/100 person-years, vs. 24%, 5.7/100 person-years, P = 0.07; last procedure: 11%, 2.5/100 person-years, vs. 24%, 6.9/100 person-years, P = 0.01), the incidence of CVH was higher (first procedure: 8%, 1.7/100 person-years, vs. 5%, 1.2/100 person-years, P = 0.74; last procedure: 6%, 1.4/100 person-years, vs. 2%, 0.5/100 person-years, P = 0.4). The number of HFH significantly decreased in both groups after CA (HFpEF: 1 hospitalization [the first and third quartiles: 0, 1] in pre-CA, vs. 0 hospitalizations [0, 0] in post-CA, P 0.0001; systolic HF: 1 hospitalization [0, 1], vs. 0 hospitalizations [0, 0], P 0.005). The proportion of HFH among total clinical events was significantly smaller in patients with HFpEF than in those with systolic HF (following the first procedure: 56% vs. 88%, P 0.005; last procedure: 52% vs. 92%, P 0.005).CA for AF could be beneficial for patients with HFpEF, similar to those with systolic HF. However, clinical events other than HFH should be considered cautiously in such patients.

Background This study aimed to investigate the correlation between left atrial low‐voltage areas (LVAs) and an arrhythmogenic superior vena cava (SVC) and the impact on the efficacy of an empiric SVC isolation (SVCI) along with a pulmonary vein isolation (PVI) of non‐paroxysmal atrial fibrillation (non‐PAF) with or without LVAs. Methods We retrospectively enrolled 153 consecutive patients with non‐PAF who underwent a PVI alone (n = 51) or empiric PVI plus an SVCI (n = 102). Left atrial voltage maps were constructed during sinus rhythm to identify the LVAs (, The LVAs was associated with an arrhythmogenic SVC in non‐PAF patients. An SVCI compensated for an impaired outcome after PVI in non‐PAF patients with LVAs.

Aims: The feasibility of offline optical coherence tomography (OCT) guidance in bifurcation (with either two-dimensional or three-dimensional images) and its potential benefits have been demonstrated in retrospective studies; however, these have not yet been investigated prospectively. The aim of this trial is to determine the superiority of online three-dimensional optical frequency domain imaging (3D-OFDI)- guided stenting to angiography-guided percutaneous coronary intervention (PCI) in terms of incomplete stent apposition (ISA) at the bifurcation segment. Methods and results: The OPTIMUM trial is a randomised, superiority, multicentre clinical trial. The primary endpoint of this trial is the post-procedural percentage of malapposed struts assessed by OFDI in the main branch bifurcation region after final kissing balloon dilatation (FKBD). A total of 106 patients will be randomly allocated to either 3D-OFDI guidance or angiography guidance PCI. Bifurcation lesions will be treated with a provisional single-stent strategy using the Ultimaster sirolimus-eluting stent. Patients randomised to the 3D-OFDI guidance arm will undergo OFDI assessment in the main branch (MV) after rewiring into the jailed side branch following stent implantation, while in the angiography guidance arm re-crossing of a wire into the side branch will be performed using conventional fluoroscopic/angiographic guidance. In patients in the 3D-OFDI guidance arm, if the position of the wire is not located in the optimal cell, further attempts to redirect the wire to the optimal cell will be performed, with subsequent OFDI acquisitions to confirm the re-crossing position. The proximal optimisation technique and FKBD are mandatory in this trial. The study will provide a 90% power to show superiority of 3D-OFDI guidance PCI compared with angiography-guided PCI. Conclusions: The OPTIMUM trial will be the first prospective, randomised trial to evaluate the efficacy and safety of online 3D-OFDI-guided PCI in bifurcation lesions. ClinicalTrials.gov Identifier: NCT02972489.

Introduction: The augmentation index (AIx) or central systolic blood pressure (SBP), measured by radial applanation tonometry, has been reported to be independently associated with left ventricular hypertrophy (LVH) in Japanese hypertensive patients. Cuff-based oscillometric measurement of the AIx using Mobil-O-Graph® showed a low or moderate agreement with the AIx measurement with other devices. Methods: The AIx measured using the Mobil-O-Graph was validated against the tonometric measurements of the radial AIx measured using HEM-9000AI in 110 normotensive healthy individuals (age, 21–76 years; 50 men). We investigated the relationship between the central hemodynamics assessed using the Mobil-O-Graph and LVH in 100 hypertensive patients (age, 54–75 years; 48 men), presenting a wall thickness of ≥11 mm and ≥10 mm in men and women, respectively. Results: Although the Mobil-O-Graph-measured central AIx showed no negative values, it correlated moderately with the HEM-9000AI-measured radial AIx (r = 0.602, p < 0.001) in the normotensive individuals. The hypertensive patients did not show a significant difference in the central SBP between the sexes, but the central AIx was lower in men than in women. The independent determinants influencing left ventricle (LV) mass index (LVMI) (R2 = 0.362; adjusted R2 = 0.329, p < 0.001) were heart rate (β = −0.568 ± 0.149, p < 0.001), central SBP (β = 0.290 ± 0.100, p = 0.005), and aortic root diameter (β = 1.355 ± 0.344, p = 0.001). Age (β = −0.025 ± 0.124, p = 0.841) and the central AIx (β = 0.120 ± 0.131, p = 0.361) were not independently associated with the LVMI. The area under the receiver operator characteristic curve to evaluate the diagnostic performance of the central AIx for the presence of LVH (LVMI >118 g/m2 in men or >108 g/m2 in women) was statistically significant in men (0.875, p < 0.001) but not in women (0.622, p = 0.132). In men, a central AIx of 28.06% had a sensitivity of 83.3% and specificity of 80.0% for detecting LVH. Conclusions: AIx measurement in men provided useful prognostic information for the presence of LVH. Pulse-wave analysis assessed using the Mobil-O-Graph may be a valuable tool for detecting LVH in hypertensive patients.

Background Leakage of Ca2+ from the sarcoplasmic reticulum (SR) is a critical contributing factor to heart failure pathophysiology. Therefore, reducing SR Ca2+ leaks may provide significant additive benefits when used in combination with conventional therapies. Dantrolene, a drug routinely used to treat malignant hyperthermia, also stabilizes the cardiac isoform of the release channel (RyR2), thus decreasing SR Ca2+ leaks. The purpose of this study is to evaluate the effect of chronic administration of dantrolene on heart failure and lethal arrhythmia in patients with chronic heart failure and reduced ejection fraction in a multicenter, randomized, double-blind, controlled study. Methods Patients with chronic heart failure who had functional status of New York Heart Association class II and III and a left ventricular ejection fraction Results This paper presents the rationale and trial design of the study. Recruitment for the study started on 8 December 2017. Conclusions The results of this trial will clarify the efficacy and safety of dantrolene for ventricular arrhythmia, as well as mortality and morbidity in patients with chronic heart failure and reduced ejection fraction during guideline-directed medical treatment.

Transcatheter aortic valve implantation (TAVI) is increasingly being performed in very elderly patients, although its efficacy and validity remain unclear. This study evaluated real-world TAVI outcomes in Japanese nonagenarians with severe aortic stenosis.Methods and Results: This single-center study retrospectively assessed the early and long-term clinical outcomes of TAVI in nonagenarians (n=35) and in patients aged90 years (group Y; n=171). There were no in-hospital deaths in either group. The device success rate and early safety were comparable between the 2 groups. The 5-year rates of freedom from cardiac events and deaths were equivalent in both groups. The cumulative survival rate at 5 years was non-significantly lower in nonagenarians (32.6% in nonagenarians vs. 57.5% in patients aged90 years, P=0.49). There were no differences in the 5-year survival between nonagenarians after TAVI and the sex- and age-matched populations (P=0.18). The Cox regression model revealed that lower hemoglobin levels were associated with all-cause mortality (P=0.02), and age ≥90 years was not associated with all-cause mortality.The early and long-term clinical outcomes of TAVI for selected Japanese nonagenarians were comparable to those in patients aged90 years. Nonagenarians who underwent TAVI achieved an acceptable prognosis compared to the sex- and age-matched population; thus, TAVI appears to be effective for treating aortic stenosis in Japanese nonagenarians.

Background Catheter ablation can improve long‐term prognosis of patients with atrial fibrillation with systolic impairment. However, atrial tachyarrhythmia (ATA) recurrence increases during long‐term follow‐up. We aimed to investigate the impact of ATA recurrence on the development of long‐term adverse clinical events following catheter ablation for atrial fibrillation and to identify predictors for the development of adverse clinical events. Methods and Results This single‐center observational study included 75 patients with systolic impairment (left ventricular ejection fraction P P Conclusions ATA recurrence following catheter ablation procedure could predict adverse clinical events in patients with atrial fibrillation with systolic impairment.

Background Second-generation cryoballoon (2G-CB) ablation is highly effective for achieving pulmonary vein isolation (PVI) with a promising clinical outcome. However, the ideal freezing strategy for preventing gastroesophageal excessive transmural injury (ETI) remains under debate. This study aimed to clarify the correlation between gastroesophageal ETI and a bonus-freeze protocol after PVI using 2G-CBs. Method This study included 100 patients who underwent PVI using 2G-CB followed by an endoscopic examination. The freeze-cycle duration was set at 180 s. In the first 33 patients a 120 s bonus-freeze was applied after successful PVI (bonus group), while in the following 67 the bonus freeze was omitted (non-bonus group). Early freezing interruption was performed when the esophageal temperature reached 25 °C. Gastroesophageal ETI was defined as any injury that resulted from the PVI, including esophageal damage or periesophageal nerve injury. Results Gastroesophageal ETIs were observed in 9 (27.3%) and 6 (9.0%) patients and were all asymptomatic, esophageal damage in 3 and 0, and periesophageal nerve injury in the remaining 6 and 6 in the bonus group and non-bonus group, respectively (p = 0.033). In the multivariate analysis, the bonus freeze protocol (odds ratio 3.527; 95% confidence interval 1.110–11.208; p = 0.033) was the sole independent predictor of gastroesophageal ETI. During a one-year follow-up 26 of 33 bonus group patients (78.8%) and 52 of 67 (77.6%) non-bonus group patients remained in stable sinus rhythm without any differences between the groups. Conclusions In the patients with a bonus-freeze protocol using the 2G-CB, gastroesophageal ETIs were detected more often than in those with the non-bonus freeze protocol. In contrast, freedom from atrial fibrillation after the 2G-CB based PVI was comparable when applying either a bonus or non-bonus freeze protocol.

Introduction: Transesophageal echocardiography (TEE) is the gold standard modality for detecting a thrombus in the left atrium (LA) and the left atrial appendage (LAA) prior to pulmonary vein isolation (PVI) for the treatment of atrial fibrillation. Although TEE is has a good safety profile, it was recently reported that TEE preceding PVI can cause esophageal mucosal injury (EMI). However, the detailed data and mechanism of EMI by TEE remain to be elucidated. Herein, we investigated the incidence and risk factors of TEE-related EMI in patients who underwent PVI for AF. Methods: This study included 262 consecutive patients who underwent PVI with preoperative TEE using a 3D TEE probe and postoperative esophagogastroduodenoscopy. The cause of EMI was classified by an experienced gastroenterologist. Results: TEE-related EMI was found in 16 (6.1%) patients, whereas PVI-related EMI was found in 5 (1.9%) patients. Only one patient with TEE-related EMI experienced mild chest discomfort. In the multivariate analysis, advanced age was an independent risk factor for TEE-related EMI (odds ratio, 1.08 per 1-year increment; 95% confidence interval, 1.01-1.16; p = 0.0274). Conclusions: The incidence of TEE-related EMI, for which advanced age could be a significant risk factor, using a 3D TEE probe was relatively high in patients who underwent PVI. This study suggests that attention should be paid to the indications of TEE before performing PVI, especially in elderly patients, and other modalities for ruling out LA and LAA thrombus should also be considered.

Background Functional mitral regurgitation (FMR) is not uncommon in atrial fibrillation (AF) patients. Left atrial (LA) substrate remodeling and corresponding mitral valve annulus dilation has been reported as the most possible cause of FMR. Percutaneous catheter ablation (CA) is an effective treatment for AF. Although significant FMR could be improved by sinus restoration, patients with mitral regurgitation were more likely to experience recurrent AF post ablation, especially those with significant mitral regurgitation. There is no information available on the efficacy of CA for persistent AF in patients with FMR. Purpose The purpose of this study is to investigate the predictors of FMR improvement by CA and to determine the efficacy of substrate and trigger CA for persistent AF in patients with FMR. Methods We prospectively studied 512 consecutive patients admitted for persistent AF ablation from the EARNEST-PVI (Prospective Multicenter Randomized Study of Effect of Extensive Ablation on Recurrence in Patients with Persistent Atrial Fibrillation Treated with Pulmonary Vein Isolation) trial. On admission, enrolled patients were randomly assigned in a 1:1 ratio to pulmonary vein isolation (PVI) or PVI-plus additional ablation (linear ablation or/and CFAE ablation). Of the 512 patients, we studied 94 patients with preoperative echocardiography showing moderate or greater baseline FMR. FMR grades were classified into 5 grades (0/1/2/3/4). The FMR improvement group (FMRI(+)) was defined as a case in which the FMR was improved by two or more grades compared the preoperative echocardiography and the one year follow-up examination. Results Of the 94 patients, 42 were in the PVI group and 52 were in the PVI-plus additional ablation group. There were 30 cases in the FMRI(+) group and 64 cases in the FMRI(−) group. There were no significant baseline differences in age, sinus rhythm maintenance, plasma B-type natriuretic peptide (BNP) level, left ventricular diastolic dimension, or left atrium dimension between the FMRI(+) and FMRI(−) groups. AF duration was significantly shorter in the FMRI(+) group than FMRI(−) groups (5.8±9.4 months vs 12.4±15.4 months, p Conclusions Catheter ablation is a valid option for the treatment of AF in patients with functional MR and additional substrate and trigger ablation were the only independent predictor of FMR improvement. Funding Acknowledgement Type of funding sources: None.

Background Clinical heterogeneity exists in heart failure with preserved ejection fraction (HFpEF). Left ventricular (LV) structure in HFPEF is characterized by normal LV cavity size and LV hypertrophy (LVH). However some of HFPEF patients do not have LV hypertrophy, and these patients may have distinct characteristics, Purpose The purpose of this study is to clarify the clinical characteristics and the prognosis for HFPEF patients without LVH. Methods We studied 1097 patients, who were hospitalized for acute decompensated heart failure with LVEF ≥50%, and enrolled in the PURSUIT-HFpEF registry. Laboratory testing and echocardiography were examined in the compensated stage (in stable condition after treatment of acute decompensated HF). We divided these patients into 2 groups based on LV mass index (LVMI) in the compensated stage according to the American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations; patients with LVH (48%) and those without LVH (52%). Results Patients without LVH had significantly lower levels of C-reactive protein and N-terminal pro brain natriuretic peptide (NT-proBNP) and higher levels of estimated glomerular filtration rate in the compensated stage than those with it (p On the other hand, the frequency of atrial fibrillation (Af) in the decompensated stage was higher in patients without LVH than those with it (52.1% vs 39.3%, p Conclusions HFPEF patients without LVH have less organ damage and favorable prognosis. Af may play a role in the decompensation of HF in HFPEF patients without LVH. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Roche Diagnostics K.K. (Grant number: not applicable)Fuji Film Toyama Chemical Co., Ltd. (Grant number: not applicable)

Background Diagnosing heart failure with preserved ejection fraction (HFpEF) is still challenging, and the H2FPEF- and the HFA-PEFF score were proposed as simple and reliable diagnostic tools. We recently reported that the HFA-PEFF score was significantly associated with the composite endpoint of all-cause death and heart failure readmission in patients with acute decompensated HFpEF (Sotomi. Eur J Heart Fail, in press). Purpose To investigate the relation whether the HFA-PEFF or H2FPEF score can evaluate functional capacity in patients with HFpEF Methods We calculated H2FPEF score and the second step of HFA-PEFF score among the registered patients in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study, which is a multicenter registration of patients hospitalized for acute decompensated HFpEF. We performed 6 minute walk (6MW) test and measured NT-proBNP before discharge. We followed the study patients for median of 360 days (IQR 237–630 days) to observe the major adverse cardiovascular events (MACE; composite of death, heart failure hospitalization and stroke). Results We enrolled 757 patients (age 81±9 years, male gender 45%) hospitalized for acute decompensated HFpEF for the present study. The H2FPEF score was obtained in 588 (77.7%) patients and all patients had ≥2 points. The HFA-PEFF score was obtained in 615 (81.2%) patients, though global longitudinal strain was not available. We divided these patients into 3 groups based on the HFA-PEFF score (score 2 to 4, 5, and 6) or on the H2FPEF score (score 0 to 3, 4 to 5 and 6 to 8). There were a significant difference in NT-pro BNP between 3 groups based on HFA-PEFF score (p=0.01, Table 1), and patients with score 6 had significantly higher NT-proBNP than those with score 2 to 4 (p=0.02). A significant difference was observed in 6MW distance among these groups (p=0.04, Table), and those with score 6 had significantly shorter distance than those with score 2 to 4 (p=0.04). Cox proportional hazard model selected HFA-PEFF score as a significant predictor for MACE, and Kaplan-Meier survival analysis demonstrated that classification of HFA-PEFF score significantly stratified the patients' risk for MACE. On the other hand, there was no significant difference in 6MW distance among 3 groups based on H2FPEF score (p=0.53), and H2FPEF score was not an independent predictor for MCE by the Cox model analysis. Moreover, the lowest H2PEF score group had higher NT-proBNP than other 2 groups (p=0.02) Conclusions The HFA-PEFF score predicted functional capacity as well as prognosis in patients hospitalized for HFpEF, while the H2PEF score did not. Funding Acknowledgement Type of funding sources: None. Table 1

Introduction and hypothesis Sterile inflammation is associated with cardiac remodeling in response to non-ischemic stress, but how it is initiated in the absence of cell death and how it is propagated are not well elucidated. We tested the hypothesis that activation of CaMKII in cardiomyocytes and macrophages in response to pressure overload initiates inflammatory responses leading to adverse cardiac remodeling. Methods and results Cardiomyocyte specific CaMKIIδ knockout (CKO) mice were subjected to transverse aortic constriction (TAC). CaMKII and NFkB activation were significantly increased in control fl/fl (CTL) but not in CKO hearts. Cardiac mRNA levels for pro-inflammatory cytokines also increased vs sham. These responses were significantly attenuated in the CKO mice. Activated NLRP3 inflammasome was shown by elevated caspase-1 activity in isolated cardiomyocytes of CTL while attenuated in CKO. Macrophage accumulation was attenuated in the CKO and NLRP3 inhibitor MCC950 treated mice. Cardiac fibrosis and subsequent cardiac dysfunction were less impaired in the CKO vs CTL (ejection fraction 43±3% vs 33±5%). Upregulated NLRP3 gene expression, elevated CaMKII and caspase-1 activity were observed in neonatal mouse cardiomyocytes (NMCMs) in response to osmotic stretch. Increased caspase-1 activity was observed in macrophages cultured with media from osmotic-stretched NMCMs and it was attenuated by pretreatment of CaMKII inhibitor KN-93. Coincubation with stretched NMCMs induced inflammatory responses in isolated macrophages from wild-type mice but not in isolated macrophages from KN-93 pretreated mice. Conclusions Activated CaMKIIδ in response to pressure overload triggers inflammatory signals including NLRP3 inflammasome cascade in cardiomyocytes. CaMKII could also contribute amplification of inflammasome signal in macrophages leading fibrosis and consequent cardiac dysfunction. CaMKII in cardiomyocytes and macrophages could be a therapeutic target to prevent progression of non-ischemic heart failure. Funding Acknowledgement Type of funding sources: None.

Transesophageal echocardiography (TEE) is the gold standard for detecting thrombi in the left atrium (LA) and left atrial appendage (LAA) prior to pulmonary vein isolation (PVI) for the treatment of atrial fibrillation (AF). Although TEE has a good safety profile, it was recently reported that TEE preceding PVI can cause esophageal mucosal injuries (EMIs). The exact mechanism remains to be elucidated. In the present study, we investigated the incidence and risk factors of TEE-related EMI (TEE-EMI) among patients who underwent PVI for AF.This study included 262 consecutive patients who underwent PVI with preoperative TEE using a 3D TEE probe and postoperative esophagogastroduodenoscopy. TEE-EMIs were observed in 16 (6.1%) patients (18 lesions), whereas PVI-related EMIs were found in 5 (1.9%) patients (8 lesions). All TEE-EMIs were observed in the upper or middle esophagus and occurred more frequently in the right region of the upper esophagus and the left anterior region of the middle esophagus; only one patient experienced mild chest discomfort. In the multivariate analysis, advanced age was an independent risk factor for TEE-EMIs (odds ratio 1.08, 95% confidence interval 1.01-1.16; P = 0.0274).The incidence of TEE-EMIs with 3D TEE probes was relatively high in the upper or middle esophagus, anatomically close to the LA, among patients who underwent PVI. Advanced age could pose a significant risk. These findings may warrant consideration of other methods to rule out LA/LAA thrombi, especially in elderly patients.

The three-dimensional reconstruction of optical coherence tomography and optical frequency domain imaging (3D-OCT/OFDI) helps optimize bifurcation percutaneous coronary interventions (PCIs) with side branch (SB) dilatation by identifying the optimal rewiring position. 3D-OCT/OFDI’s diagnostic performance for assessing the rewiring position into a jailed SB is unknown. We retrospectively evaluated the diagnostic performances of a conventional (ver. 1.1) and a new (ver. 1.2) online 3D-OFDI reconstruction system based on an offline 3D reconstruction system’s performance. We analyzed 45 patients’ 52 OFDI pullbacks with main vessel stenting followed by rewiring into a jailed SB for coronary bifurcation lesions. We counted the undetected stent struts in the polygon of confluence as the stent detection performance. We assessed the diagnostic agreement regarding the rewiring position into a jailed SB by the three 3D reconstruction systems. The percentage of undetected struts and the diagnostic agreement of ver.1.2 were significantly better than those of ver.1.1 [5.1 ± 5.1% vs. 30.2 ± 14.2%; p p = 0.0120]. The new online 3D-OFDI reconstruction system provides better diagnostic performance than the conventional online system for assessing the rewiring position into a jailed SB.

Physical activity (PA) in the daily life is strongly related to prognosis in patients with or at high risk of heart failure (HF). However, factors limiting habitual exercise and their prognostic impacts remain unknown in HF patients. We sent questionnaires asking factors limiting habitual exercise in the daily life to 8370 patients with Stage A/B/C/D HF in our nationwide registry and received valid responses from 4935 patients (mean age 71.8 years, 71.0% male). Among the 5 components consisting of “busyness”, “weak will”, “dislike, “socioeconomic reasons” and “diseases” in the questionnaires, “busyness” (34.5%) and “diseases” (34.7%) were the most frequently reported factors limiting habitual exercise, while “socioeconomic reasons” were the least (15.3%). Multiple Cox proportional hazard models indicated that “busyness”and “diseases” were associated with better (hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.39–0.72, P

BACKGROUND Increased heart rate (HR) is an independent risk factor for cardiovascular outcomes in chronic heart failure (HF). Ivabradine, anIfinhibitor, improved outcomes in patients with HF and reduced ejection fraction (HFrEF) in the SHIFT study. We evaluated its efficacy and safety in Japanese HFrEF patients in a randomized, double-blind, placebo-controlled phase III study: the J-SHIFT study. The main objective was to confirm a hazard ratio of

Background Transradial intervention (TRI) may cause damage to the radial artery (RA). We have demonstrated intima-media thickening and luminal narrowing of the distal RA after TRI using intravascular ultrasound (IVUS). This study aimed to determine the predictors of intima-media thickening of RA after TRI in the same patients using serial IVUS. Methods and results We enrolled 110 consecutive patients who underwent TRI. IVUS of RA was immediately performed after TRI and repeated 6 months later. Volumetric analyses were performed for the distal RA. The intima-media volume (IMV) increased from 53.56 ± 10.85 mm3 to 58.70 ± 13.04 mm3 (p = 0.0022), whereas the lumen volume (LV) decreased from 146.87 ± 40.53 mm3 to 129.64 ± 45.78 mm3 (p = 0.0018) and vessel volume (VV) decreased from 201.23 ± 44.55 mm3 to 188.34 ± 52.25 mm3 (p = 0.0306). Multiple regression analysis revealed diabetes as the most powerful independent predictor of the percentage change in IMV of the distal RA after TRI. The percentage change in IMV significantly increased in the DM group compared with non-DM group (p Conclusions Serial IVUS of the distal RA revealed a significant increase in IMV and decreases in LV and VV. Diabetes was the most powerful independent predictor of the percentage change in IMV of the distal RA after TRI. The percentage change in IMV was significantly positively correlated with HbA1c.

BACKGROUND An association between atrial high-rate episode (AHRE) and stroke has been reported, although data for the Asian population are limited. This study aimed to investigate the role of AHRE in ischemic and major bleeding events in patients who underwent a cardiac implantable electronic device (CIED) procedure.Methods and Results:This single-center historical cohort study included 710 patients (age: 78±11 years, 374 women) who underwent a CIED-related procedure between October 2009 and September 2019 at Shimane Prefectural Central Hospital (median follow-up period: 4.5 [2.5, 7] years, 3439 person-years). Based on the maximum AHRE burden, patients were divided into: (1)

Background In developed countries, the incidence of non-ST-segment elevation myocardial infarction (NSTEMI) has outpaced that of ST-segment elevation myocardial infarction (STEMI). However, whether this trend is observed in Japan, in which the aging of society is rapidly progressing, remains to be elucidated.Methods and Results:This study retrospectively investigated the trends over time in the incidence of acute coronary syndrome (ACS) between August 2009 and July 2019 at 2 institutions in Izumo City (in rural Japan), which has an elderly population. Crude and age-sex-adjusted incidences of total ACS, STEMI, and non-ST-segment elevation-ACS (NSTE-ACS; including NSTEMI and unstable angina pectoris) were calculated for each year. In the total population, factors associated with the development of NSTEMI were evaluated by multivariate analysis. In total, 1,087 patients were enrolled. The age-adjusted incidence of NSTE-ACS in male patients aged ≥75 years showed a significantly increasing trend. The proportion of NSTEMI per total ACS cases showed a significantly increasing trend over the entire study period. In the multivariate analysis, pre-development use of ≥3 medications for comorbidities was associated with the development of NSTEMI, independent of high-sensitivity cardiac troponin assay use. Conclusions This study demonstrated an increasing trend in the incidence of NSTEMI in a rural high-aged Japanese population. In addition to the widespread use of high-sensitivity cardiac troponin assays, early medication use for comorbidities might have contributed to this trend.

Background Diagnosing heart failure with preserved ejection fraction (HFpEF) still remains challenging, and simple and reliable diagnostic tools have been required. Recently, novel and evidence-based diagnostic algorithms for HFpEF were proposed, such as H2FPEF score (Circulation. 2018) and HFA-PEFF score (Eur Heart J 2019), and their accuracy was validated in the outside patient group. However, there are regional and ethnic variations in patient characteristics of HFpEF, particularly between Western and Asian countries, and it is not elucidated whether these diagnostic scores are useful in Asian population. Purpose To investigate the validity of the HFA-PEFF- and H2FPEF score in Japanese patients with HFpEF. Methods We calculated H2FPEF score and the second step of HFA-PEFF score among the registered patients in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study, which is a multicenter registration of patients hospitalized for HFpEF. The obtained scores were compared with the scores of the HFpEF cohort in the previous validation studies. We followed the study patients for median of 360 days (IQR 237–630 days) to observe the major adverse cardiovascular events (MACE; composite of death, heart failure hospitalization and stroke). Results We enrolled 757 patients hospitalized for HFpEF between June 2016 and August 2019 for the present study. H2FPEF score was obtained in 588 (77.7%) patients among them. Compared with the HFpEF cohorts in the previously reported sub-analysis of TOPCAT trial, the PURSUIT-HFpEF cohort had lower mean value of HFpEF score (4.0±1.8 points vs. 6.0±2.0 points in Americans or 5.3±1.9 points in Russians). It had significantly higher proportion (40.3%, p HFA-PEFF score was obtained in 615 (81.2%) patients, though global longitudinal strain was not available. The mean value of HFA-PEFF score was 5.0±0.8, and all patients had ≥2 points. The proportion of patients in the high likelihood of HFpEF category (5–6 points) was 88.3%, which was significantly higher (p Conclusion The HFA-PEFF score could be more useful for the diagnosis and risk stratification for HFpEF than the H2PEF score in the Japanese cohort. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K.; Fuji Film Toyama Chemical Co. Ltd.

Background Malnutrition is one of the most important comorbidities among heart failure (HF) patients, and serum cholinesterase (CHE) has been reported to be a prognostic factor in HF patients. On the other hand, atrial fibrillation (AF) is frequently observed in patients with HF with preserved ejection fraction (HFpEF). However, there is little information available on the prognostic value of nutritional status in HFpEF patients, with and without AF. We sought to clarify the prognostic value of CHE in HFpEF with and without AF and compare it with that of other nutrition indices such as gastric nutritional risk index (GNRI), controlling nutritional status (CONUT), and the prognostic nutritional index (PNI). Methods and results Patients data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study, which is a prospective multicenter observational registry for acute decompensated heart failure patients with left ventricular ejection fraction ≥50% in Osaka. We analyzed 380 patients (median age: 80 [75–87] years, male: 46%) after exclusion of patients with in-hospital death, missing follow-up data, or missing data to calculate nutritional indices. On admission, 155 patients had AF. Laboratory data were obtained at discharge. During a mean follow up period of 1.1±0.6 years, 131 patients had a composite endpoint (CE) of all-cause death and hospitalization for worsening heart failure or cerebrovascular disorder. In multivariate Cox analysis, in patients with AF, CHE was significantly associated with CE independently of age, gender and body mass index after the adjustment with serum albumin, total cholesterol levels and total lymphocyte count, while it was not significantly associated with CE in patients without AF. C-index of CHE (0.708) was higher than that of GNRI (0.555, p=0.0028), CONUT (0.651, p=0.208) and PNI (0.635, p=0.208) in AF patients, while there were no significant differences in those nutritional indices in patients without AF. Kaplan-Meier curve analysis revealed that AF patients with lower CHE ( Conclusions Prognostic value of CHE would be stronger than other nutritional indices in HFpEF patients with AF, while it would be weak in HFpEF patients without AF. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K.; Fuji Film Toyama Chemical Co. Ltd.

Background Heart failure (HF) with preserved ejection fraction (HFpEF) can develop pulmonary hypertension (PH), which can result from pre-capillary PH as well as post-capillary PH. However, the prevalence and clinical significance of pre-capillary component of PH in HFpEF remain unknown. Purpose We aimed to investigate prevalence, clinical features, and prognostic impact of pre-capillary and/or post capillary PH associated with HFpEF. Methods From the PURSUIT-HFpEF (Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) registry, 204 patients (men: 46%, age: 79±9 years) who were hospitalized with HF and underwent right heart catheterization were divided into 4 groups according to the PH guidelines: non-PH, isolated post-capillary PH (Ipc-PH), pre-capillary PH, and combined pre- and post-capillary PH (Cpc-PH). Patients who had been diagnosed with idiopathic pulmonary arterial hypertension were excluded from the analysis. Results The prevalence of PH was 31% (Ipc-PH: 22%, pre-capillary PH: 3%, Cpc-PH: 6%). The prevalence of subcategories of PH was significantly different depending on mean right atrial pressure (RAP) (figure). Echocardiography at discharge showed no significant differences in RV diameter or TAPSE, but smaller LV diameter and higher E/e' in pre-capillary PH and Cpc-PH, which resulted in a higher operant diastolic elastance (Ed). Composite endpoint of all-cause mortality and HF hospitalization at 1 year occurred 13% in non-PH, 25% in Ipc-PH, 49% in pre-capillary PH, and 63% in Cpc-PH, respectively (p=0.001 by log-rank test). Conclusions Distinct prevalence of PH was observed in the groups with different RAP levels. Pre-capillary component of PH was associated with impaired LV diastolic function and worse outcomes in HFpEF. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K.; Fuji Film Toyama Chemical Co. Ltd

Background The novel nutrition index; triglyceride (TG) × total cholesterol (TG) × body weight (BW) index (TCBI) has been reported to be an easy and useful predictor for patients with coronary artery disease. However, there is no information available on the prognostic value of TCBI in patients with heart failure with preserved LVEF (HFpEF) who admitted with acute decompensated heart failure (ADHF). Methods and results Data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study. PURSUIT-HFpEF study is a prospective multicenter observational study in which collaborating hospitals recorded clinical, echocardiographic, and outcome data of ADHF pts with HFpEF. We enrolled consecutive 757 HFpEF patients who admitted with ADHF from June 2016 to June 2019. TCBI was calculated by the formula; TG × TC × BW / 1000 at the discharge. After we excluded patients with in-hospital death or without sufficient data, we analyzed 419 patients. The primary endpoint was all-cause mortality. During a median follow up period of 1.1 (0.9–1.9) years, 59 patients died. ROC analysis revealed that TCBI at discharge was a fair discriminator for predicting all-cause mortality (AUC 0.676, sensitivity 53%, specificity 78%). Multivariate Cox proportional analysis showed that TCBI (p=0.002) was an independent predictor for all cause death after adjustment with major confounders such as age, gender, NT-proBNP, hemoglobin and serum creatinine level. We divided patients into 4 groups according to quartiles of TCBI. Kaplan-Meier analysis showed a significantly higher risk of all-cause death in relation to the decrease in TCBI. Conclusion TCBI, a simple and novel nutrition index, is a useful and strong long-term prognostic indicator in ADHF patients with HFpEF. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnositics K.K.; Fuji Film Toyoma Chemical Co. Ltd.

Introduction Frailty and aging are two common conditions both associated with increased vulnerability to stressful events with high risk of adverse outcomes. Purpose To evaluate the association between frailty and aging and their impacts on clinical outcome in patients with heart failure with preserved ejection fraction (HFpEF). Methods Analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 757 patients hospitalized for acute heart failure (diagnosed by using Framingham criteria) met the inclusion criteria: a left ventricular ejection fraction ≥50% and brain natriuretic peptide ≥100pg/ml. We included 483 patients (age, 80±9 years; men, 45%; atrial fibrillation, 35%) whose follow-up data after survival discharge were available. Patients' frailty and aging were evaluated using the clinical frailty scale (CFS) and age quartiles (Q1: 87 years (n=123)), respectively. The primary clinical endpoint was defined as the composite of death, re-hospitalization for heart failure, and cerebrovascular accident. Results The median (interquartile range) CFS rating was 3 (2–5), and there was a little correlation between CFS rating and age (r2=0.16, p4 (n=132), was positively correlated with age quartiles (Q1: 9.0%, Q2: 21.4%, Q3: 29.9%, Q4: 48.0%, p Conclusions Frailty was common and was associated with aging in HFpEF patients. Although they were both associated with unfavorable events, aging was no longer a significant predictor of adverse outcomes under the frailty conditions. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K. and Fuji Film Toyama Chemical Co. Ltd.

Introduction Structural remodeling is an important aspect of pathophysiology of heart failure (HF). The compensatory mechanism against diastolic dysfunction would be more obvious on the left atrium rather than left ventricle in HF with preserved ejection fraction (HFpEF). Purpose To investigate the impact of left atrial (LA) and left ventricular (LV) remodeling on clinical outcomes in HFpEF patients. Methods Analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 757 patients hospitalized for acute HF (diagnosed by using Framingham criteria) met the inclusion criteria: a LV ejection fraction ≥50% and brain natriuretic peptide ≥100pg/ml. We included 381 patients (age, 82±9 years; men, 45%; atrial fibrillation (AF), 34%) whose follow-up data after survival discharge were available and whose LA volume index (LAVI) and left ventricular end-diastolic volume index (LVEDVI) at discharge were measured by the biplane Simpson's method using echocardiography. The primary endpoint was defined as the composite of death, re-hospitalization for HF, and cerebrovascular accident. Results The LAVI and LVEDVI at discharge was 54±25 ml/m2 and 55±21 ml/m2, respectively (r2=0.014, p=0.021). When patients were classified into the LAVI tertiles groups (T1: 60ml/m2 (n=130)), there was a positive correlation between the prevalence of diastolic dysfunction and the LAVI tertiles (T1, 21.0%; T2, 48.8%; T3, 51.5%; p Conclusions Increased LAVI at discharge, which was associated with diastolic dysfunction, related to unfavorable prognosis in patients with HFpEF. However, LAVI was no more a predictor for the adverse outcomes but LVEDVI was in the AF subgroup. The clinical significance of atrial and ventricular remodeling may differ between sinus rhythm and AF rhythm in HFpEF population. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K. and Fuji Film Toyama Chemical Co. Ltd.

Background Frailty is associated with malnutrition and poor prognosis in patients with heart failure with preserved ejection fraction (HFpEF). However, the cardiac factors associated with frailty have not been fully examined in patients with HFpEF. Purpose The purpose of this study is to clarify the cardiac factors related to frailty in patients with HFpEF. Methods Of the 756 patients who registered prospective, multicenter, observational study of patients with HFpEF (PURSUIT-HFpEF) registry, 481 cases with clinical frailty score (CFS) and prognosis after discharge were examined. Frailty was defined as CFS ≥5. Outcomes were composite endpoint of all-cause death and heart failure readmission, and all-cause mortality. We compared outcomes between patients without and with frailty, and sought to identify factors which were associated with increase in clinical frailty score by the correlation analysis and linear regression analysis. Results Of 481 patients, 131 patients (27.2%) were frail. Male gender was less in patients with frailty than those without frailty (26.7% vs 73.3%, P Conclusion Our results suggest that not only nutritional factors but also a cardiac factor were associated with frailty, and frailty was associated with mortality in patients with HFpEF. Improvement of hemodynamics in HFpEF patients as well as improvement of nutrition might contribute to alleviation of frail in HFpEF patients. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K.; Fuji Film Toyama Chemical Co. Ltd.

BACKGROUND An effective catheter ablation strategy, beyond pulmonary vein isolation (PVI), for persistent atrial fibrillation (AF) is necessary. Pulmonary vein (PV)-reconduction also causes recurrent atrial tachyarrhythmias. The effect of the PVI and additional effect of a superior vena cava (SVC) isolation (SVCI) was strictly evaluated. METHODS Seventy consecutive patients with persistent AF who underwent a strict sequential ablation strategy targeting the PVs and SVC were included in this study. The initial ablation strategy was a circumferential PVI. A segmental SVCI was only applied as a repeat procedure when patients demonstrated no PV-reconduction. RESULTS After the initial procedure, persistent AF was suppressed in 39 of 70 (55.7%) patients during a median follow-up of 32 months. After multiple procedures, persistent AF was suppressed in 46 (65.7%) and 52 (74.3%) patients after receiving the PVI alone and PVI plus SVCI strategies, respectively. In 6 of 15 (40.0%) patients with persistent AF resistant to PVI, persistent AF was suppressed. The persistent AF duration independently predicted persistent AF recurrences after multiple PVI alone procedures [HR: 1.012 (95% confidence interval: 1.006-1.018); p

Background Ryanodine receptor (RyR2) is known to be a causal gene of catecholaminergic polymorphic ventricular tachycardia (CPVT), an important inherited disease. Some of the human CPVT-associated mutations have been found in a domain (4026-4172) that has EF hand motifs, the so-called calmodulin (CaM)-like domain (CaMLD). Objective The purpose of this study was to investigate the underlying mechanism by which CPVT is induced by a mutation at CaMLD. Methods A new N4103K/+ knock-in (KI) mice model was generated. Results Sustained ventricular tachycardia was frequently observed after infusion of caffeine plus epinephrine in KI mice. Endogenous CaM bound to RyR2 decreased even at baseline in isolated KI cardiomyocytes. Ca 2+ spark frequency (CaSpF) was much higher in KI cells than in wild-type cells. Addition of GSH-CaM (higher affinity CaM to RyR2) significantly decreased CaSpF. In response to isoproterenol, spontaneous Ca 2+ transient (SCaT) was frequently observed in intact KI cells. Incorporation of GSH-CaM into intact KI cells using a protein delivery kit decreased SCaT significantly. An assay using a quartz crystal microbalance technique revealed that mutated CaMLD peptide showed higher binding affinity to CaM binding domain (CaMBD) peptide. Conclusion In the N4103K mutant, CaM binding affinity to RyR2 was significantly reduced regardless of beta-adrenergic stimulation. We found that this was caused by an abnormally tight interaction between CaMBD and mutated CaM-like domain (N4103K-CaMBD). Thus, CaMBD–CaMLD interaction may be a novel therapeutic target for treatment of lethal arrhythmia.

Aims We evaluated the influence of the jailing configuration and guidewire rewiring position in front of the side-branch (SB) ostium before kissing balloon inflation (KBI) against side-branch ostial area (SBOA) at follow-up using 3D optical coherence tomography (3D-OCT). Methods and results We retrospectively analysed the cases of the 37 consecutive patients who underwent main-vessel (MV) stenting with KBI for coronary bifurcation lesion under OCT guidance and the follow-up OCT 6-12 months. We divided the patients into two groups, considering both the jailing configuration and the rewiring position by 3D-OCT. We defined the cases that achieved both the distal rewiring and link-free carina configuration as the FCD group, and the other cases were defined as the Non-FCD group. We compared the differences in the SBOA derived by the cut-plane analysis and the number of compartments between the two groups. The median and interquartile range of serial change and percent serial change in SBOA in the FCD group were significantly larger than those in the Non-FCD group [0.43 mm2 (-0.29 to 0.91) vs. -0.65 mm2 (-1.33 to 0.34); P = 0.0136 and 9.47% (-8.37 to 27.33) vs. -13.77% (-31.64 to 10.88); P = 0.0182]. Conclusion This serial OCT study demonstrated that the achievement of both the distal rewiring and link-free carina configuration may be important for the preservation of the SBOA after MV stenting with KBI for coronary bifurcation lesions.