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Abstract Background The Mt FUJI study was a multicenter, prospective, randomized, single‐blind, controlled trial comparing delivery catheter‐based and stylet‐based right ventricular (RV) lead placement at the RV septum. This study extended the follow‐up duration to 1 year after implantation. Methods Seventy patients with pacemaker indications for atrioventricular block were randomly assigned to the delivery catheter and stylet groups. We compared the mid‐term efficacy and safety between the two groups at 1 year after implantation. The primary outcome was the change in the left ventricular ejection fraction (LVEF), and the secondary outcomes were changes in brain natriuretic peptide (BNP) levels, lead parameters, paced QRS duration, and the incidence of adverse events. Results At the 1‐year follow‐up, no significant differences were observed in the changes in the LVEF (+1.0% ± 8.6% vs. +3.1% ± 8.1%, p = .332), BNP levels (+8.0 [−11.1, 26.5] pg/mL vs. −8.7 [−15.3, 13.2] pg/mL, p = .193), or lead performance between the delivery catheter and stylet groups. The QRS duration was significantly shorter in the delivery catheter group than in the stylet group (128 ± 23 ms vs. 146 ± 17 ms, p

Background: Nonsteroidal immunosuppressive therapy is a potential therapeutic strategy for cardiac sarcoidosis. However, it is not recommended as an established treatment option. This study aimed to demonstrate the clinical outcomes of patients with cardiac sarcoidosis using nonsteroidal immunosuppressants through the ILLUstration of the Management and PrognosIs of JapaNese PATiEnts with Cardiac Sarcoidosis multicenter retrospective registry. Methods: From a cohort of 512 patients, 426 who received corticosteroid therapy and 26 who received other immunosuppressive therapy were included for analysis. Clinical outcomes included all-cause death, fatal ventricular arrhythmic events (FVAE), and worsening heart failure with hospitalization. Results: Nonsteroidal immunosuppressants were used for retained fluorodeoxyglucose uptake in the heart (n = 14), corticosteroid side effects (n = 7), ventricular arrhythmia (n = 4), complete atrioventricular block (n = 2), worsened extracardiac sarcoidosis (n = 2), and other reasons (n = 2). They comprised of methotrexate (n = 20), cyclosporine (n = 2), cyclophosphamide (n = 2), and azathioprine (n = 3). After the addition of a nonsteroidal immunosuppressant, corticosteroids were reduced in 14 of 26 patients (5 [5–17] mg), although no patient discontinued corticosteroids. Of the 14 patients, decreased fluorodeoxyglucose uptake was observed in seven at follow-up. Clinical outcomes were observed in 11 patients (42.3 %). Detected events included all-cause death in five patients (19.2 %), FVAE in four (15.4 %), and worsening heart failure with hospitalization in five (19.2 %), with some overlap. Conclusions: Nonsteroidal immunosuppressive therapy may be a possible treatment option for patients who are not stabilized with corticosteroids alone or develop corticosteroid side effects.

Abstract Background The lesion index (LSI) has been used to estimate lesion formation after radiofrequency catheter ablation. However, the impedance drop and decrease in bipolar amplitude of intracardiac electrograms, which are parameters that are traditionally used to predict effective ablation lesions, are not used to calculate LSI. Therefore, we aimed to investigate the association between LSI and traditional parameters. Methods We retrospectively investigated 1355 ablation points from 31 patients who underwent LSI‐guided pulmonary vein isolation (PVI) using TactiCath. All points were classified into 3 groups based on the impedance drop: (i) 20 Ω (n = 379). The LSI targets were 4.5 for the posterior left atrium and 5.2 for the anterior left atrium. After excluding 583 points at which it was difficult to measure the amplitude, 772 ablation points during sinus rhythm were included in the analysis of bipolar amplitude. Results The target LSI was achieved at 1177 points (86.9%). The median total impedance drop and amplitude just after ablation were 16.0 [13.0–20.0] Ω and 0.21 [0.14–0.30] mV, respectively. There were significant differences among the 3 groups in the impedance and amplitude before ablation, power, target LSI, final LSI, contact force, and interlesion distance. An impedance drop of >10 Ω or an amplitude reduction of >50% was achieved at 95% and 82% of the study points, respectively. There were no major complications at any of the ablation points. Conclusion LSI‐guided PVI seemed to be useful for making sufficient ablation lesions, as assessed by the conventional parameters of impedance and amplitude change.

BackgroundThe mortality rate of acute coronary syndrome (ACS) remains high. Therefore, patients with ACS should undergo early risk stratification, for which various risk calculation tools are available. However, it remains uncertain whether the predictive performance varies over time between risk calculation tools for different target periods. This study aimed to compare the predictive performance of risk calculation tools in estimating short- and long-term mortality risks in patients with ACS, while considering different observation periods using time-dependent receiver operating characteristic (ROC) analysis.MethodsThis study included 404 consecutive patients with ACS who underwent coronary angiography at our hospital from March 2017 to January 2021. The ACTION and GRACE scores for short-term risk stratification purposes and CRUSADE scores for long-term risk stratification purposes were calculated for all participants. The participants were followed up for 36 months to assess mortality. Using time-dependent ROC analysis, we evaluated the area under the curve (AUC) of the ACTION, CRUSADE, and GRACE scores at 1, 6, 12, 24, and 36 months.ResultsSixty-six patients died during the observation periods. The AUCs at 1, 6, 12, 24, and 36 months of the ACTION score were 0.942, 0.925, 0.889, 0.856, and 0.832; those of the CRUSADE score were 0.881, 0.883, 0.862, 0.876, and 0.862; and those of the GRACE score 0.949, 0.928, 0.888, 0.875, and 0.860, respectively.ConclusionsThe ACTION and GRACE scores were excellent risk stratification tools for mortality in the short term. The prognostic performance of each risk score was almost similar in the long term, but the CRUSADE score might be a superior risk stratification tool in the longer term than 3 years.

Cardiac involvement of eosinophilic granulomatosis with polyangiitis is a rare but life-threatening complication. We present a case of eosinophilic granulomatosis with polyangiitis with moderately impaired ventricular function forming a ventricular thrombus. Pathological assessment of endomyocardial biopsy specimen revealed aggregated eosinophils in the subendocardium, suggesting ventricular endothelial damage leading to thrombus formation.

Background: Although takotsubo syndrome (TTS) is characterized by transient systolic dysfunction of the left ventricle (LV), the time course and mechanism of LV function recovery remain elusive. The aim of this study is to evaluate cardiac functional recovery in TTS via serial cardiac magnetic resonance feature tracking (CMR-FT). Methods: In this Japanese multicenter registry, patients with newly diagnosed TTS were prospectively enrolled. In patients who underwent serial cardiovascular magnetic resonance (CMR) imaging at 1 month and 1 year after the onset, CMR-FT was performed to determine the global circumferential strain (GCS), global radial strain (GRS) and global longitudinal strain (GLS). We compared LV ejection fraction, GCS, GRS and GLS at 1 month and 1 year after the onset of TTS. Results: Eighteen patients underwent CMR imaging in one month and one year after the onset in the present study. LV ejection fraction had already normalized at 1 month after the onset, with no significant difference between 1 month and 1 year (55.8 ± 9.2% vs. 58.9 ± 7.3%, p = 0.09). CMR-FT demonstrated significant improvement in GCS from 1 month to 1 year (−16.7 ± 3.4% vs. −18.5 ± 3.2%, p < 0.01), while there was no significant difference in GRS and GLS between 1 month and year (GRS: 59.6 ± 24.2% vs. 59.4 ± 17.3%, p = 0.95, GLS: −12.8 ± 5.9% vs. −13.8 ± 4.9%, p = 0.42). Conclusions: Serial CMR-FT analysis revealed delayed improvement of GCS compared to GRS and GLS despite of rapid recovery of LV ejection fraction. CMR-FT can detect subtle impairment of LV systolic function during the recovery process in patients with TTS.

An 89-year-old man with a history of percutaneous coronary intervention using a sirolimus-eluting stent presented with recurrent in-stent occlusion. Pathological assessment of the neointima resected via directional coronary atherectomy revealed a double-layered thrombus. Clopidogrel resistance and limited antithrombotic regimen owing to high bleeding risk likely resulted in the in-stent thrombotic occlusion.

Objectives In hypertrophic cardiomyopathy (HCM), specific ECG abnormalities are observed. Therefore, ECG is a valuable screening tool. Although several studies have reported on estimating the risk of developing fatal arrhythmias from ECG findings, the use of ECG to identify the severity of heart failure (HF) by applying deep learning (DL) methods has not been established.Methods We assessed whether data-driven machine-learning methods could effectively identify the severity of HF in patients with HCM. A residual neural network-based model was developed using 12-lead ECG data from 218 patients with HCM and 245 patients with non-HCM, categorised them into two (mild-to-moderate and severe) or three (mild, moderate and severe) severities of HF. These severities were defined according to the New York Heart Association functional class and levels of the N-terminal prohormone of brain natriuretic peptide. In addition, the patients were divided into groups according to Kansas City Cardiomyopathy Questionnaire (KCCQ)-12. A transfer learning method was applied to resolve the issue of the low number of target samples. The model was trained in advance using PTB-XL, which is an open ECG dataset.Results The model trained with our dataset achieved a weighted average F1 score of 0.745 and precision of 0.750 for the mild-to-moderate class samples. Similar results were obtained for grouping based on KCCQ-12. Through data analyses using the Guided Gradient Weighted-Class Activation Map and Integrated Gradients, QRS waves were intensively highlighted among true-positive mild-to-moderate class cases, while the highlighted part was highly variable among true-positive severe class cases.Conclusions We developed a model for classifying HF severity in patients with HCM using a deep neural network algorithm with 12-lead ECG data. Our findings suggest that applications of this DL algorithm for using 12-lead ECG data may be useful to classify the HF status in patients with HCM.

Although the use of BCR-ABL1 tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia is known to cause vascular adverse events (VAEs), the frequency of VAEs during dasatinib administration is not high, and the same holds for atherosclerosis-related VAEs. However, its effect on atherosclerosis remains controversial. In this study, our primary objective was to investigate how dasatinib affects atherosclerosis. Ldlr−/−/Apobec1−/− mice, which are highly prone to develop atherosclerosis, were administered dasatinib. After 16 weeks, we evaluated their atherosclerotic lesions. We used bone-marrow-derived macrophages to investigate the uptake of oxidized low-density lipoprotein (LDL) complexed with DiI dye (DiI-oxLDL). RNA sequencing and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were performed to explore the potential effects of dasatinib on cholesterol metabolism. Dasatinib administration significantly reduced atherosclerotic lesions (P

A 56-year-old male subject with bilateral eyelid swelling was diagnosed with an immunoglobulin G4–related disease. After whole-body surveillance, concomitant coronary arteritis with a mural thrombus and myocardial involvement were observed. In this case, multimodal diagnostic imaging assessment led to the diagnosis of both coronary arteritis and myocardial fibrosis associated with immunoglobulin G4–related disease. (Level of Difficulty: Advanced.)

Background: Malnutrition in cardiovascular disease is associated with poor prognosis, especially in patients with heart failure and acute coronary syndrome (ACS). High bleeding risk is also linked to coronary artery disease prognosis, including ACS. However, whether the extent of malnutrition and high bleeding risk have a cumulative impact on the long-term prognosis of patients with ACS who undergo percutaneous coronary intervention remains unclear. Methods: We analyzed 275 patients with ACS treated with percutaneous coronary intervention. The Controlling Nutritional Status score and Japanese version of the Academic Research Consortium for High Bleeding Risk criteria (J-HBR) were retrospectively evaluated. The primary and secondary outcomes were adjusted using the inverse probability treatment weighting method. Results: The prevalence of moderate or severe malnutrition in this cohort was 16%. Kaplan–Meier analysis showed a significantly higher incidence of major adverse cardiovascular and cerebrovascular events in patients who were moderately or severely malnourished than in those who were not. Notably, the incidence of these major events was similar between severely malnourished patients with J-HBR and those without. Conclusion: Moderate or severe malnutrition has a significant impact on the long-term prognosis of patients with ACS who undergo percutaneous coronary intervention.

Abstract Objective Hypertrophic cardiomyopathy (HCM) is a common genetic disease with diverse morphology, symptoms, and prognosis. Hypertrophied myocardium metabolism has not been explored in detail. We assessed the association between myocardium lipid metabolism and clinical severity of heart failure (HF) in HCM using imaging mass spectrometry (IMS). Results We studied 16 endomyocardial biopsy (EMB) specimens from patients with HCM. Analysis was conducted using desorption electrospray ionization IMS. The samples were assigned into two cohorts according to the period of heart biopsy (cohort 1, n = 9 and cohort 2, n = 7). In each cohort, samples were divided into two groups according to the clinical severity of HF in HCM: clinically severe and clinically mild groups. Signals showing a significant difference between the two groups were analyzed by volcano plot. In cohort 1, the volcano plot identified four signals; the intensity in the clinically severe group was more than twice that of the mild group. Out of the four signals, docosahexaenoic acid (DHA) showed significant differences in intensity between the two groups in cohort 2 (10,575.8 ± 2750.3 vs. 19,839.3 ± 4803.2, P = 0.025). The intensity of DHA was significantly higher in EMB samples from the clinically severe HCM group than in those from the mild group.

Acute coronary syndromes due to atherosclerotic coronary artery disease are a leading cause of morbidity and mortality worldwide. Intra-plaque hemorrhage (IPH), caused by disruption of intra-plaque leaky microvessels, is one of the major contributors of plaque progression, causing a sudden increase in plaque volume and eventually plaque destabilization. IPH and its healing processes are highly complex biological events that involve interactions between multiple types of cells in the plaque, including erythrocyte, macrophages, vascular endothelial cells and vascular smooth muscle cells. Recent investigations have unveiled detailed molecular mechanisms by which IPH leads the development of high-risk “vulnerable” plaque. Current advances in clinical diagnostic imaging modalities, such as magnetic resonance image and intra-coronary optical coherence tomography, increasingly allow us to identify IPH in vivo. To date, retrospective and prospective clinical trials have revealed the significance of IPH as detected by various imaging modalities as a reliable prognostic indicator of high-risk plaque. In this review article, we discuss recent advances in our understanding for the significance of IPH on the development of high-risk plaque from basic to clinical points of view.

Abstract Introduction Conventional Doppler measurements have limitations in predicting left ventricular diastolic dysfunction (LVDD) in patients with mitral regurgitation (MR). Recently, electrocardiographic P‐wave peak time (PWPT) has been proposed as a parameter of detecting LVDD. This study aimed to evaluate the association between PWPT and left ventricular end‐diastolic pressure (LVEDP) in patients with MR. Methods We performed echocardiography and cardiac catheterization in 82 patients with moderate or severe MR. We classified patients into two groups: low LVEDP group (L‐LVEDP) (LVEDP

Objective We sought to investigate whether it is possible to obtain individualised left anterior oblique (LAO) by preprocedural electrocardiographic parameters and, if so, whether these parameters can help to improve the success rate of right ventricular (RV) lead implantation into the interventricular septum.Methods In this observational study, we assessed the relationship between preoperative electrocardiographic parameters and the angle of the interventricular septum obtained using thoracic CT. The participants were divided into two groups: a retrospective derivation cohort to derive the optimal formula for the individual septum axis, and a prospective internal validation cohort to which we applied the optimal formula and implanted using the new method.Results In the retrospective derivation cohort (n=39), the mean angle of individualised LAO assessed by thoracic CT was 53.1°±8.9°, and the preoperative ECG QRS axis was strongly correlated with the interventricular septum axis (R2=0.490). LAO projection derived from the preoperative ECG QRS axis confirmed that the RV lead was placed in the interventricular septum during the pacemaker procedure in the prospective internal validation group (n=30). The success rate for placing the RV lead into the interventricular septum was significantly improved in the internal validation cohort (93% vs 64%, p

Background: The guideline-recommended low-density lipoprotein cholesterol target level of p = 0.498). The two groups showed no significant differences in hospitalization for worsening heart failure and adverse events. Conclusions: In ACS patients who underwent PCI, short-term PCSK9 antibody therapy with conventional LLT was feasible in this pilot clinical trial. Long-term follow-up in a larger scale clinical trial is warranted.

Abstract Background The hemodynamics in the left ventricle (LV) and the ascending aorta (AAO) before and after alcohol septal ablation (ASA) in patients with hypertrophic obstructive cardiomyopathy (HOCM) is elucidated. Our objective was to evaluate the pattern changes in AAO and intra-LV flow assessed by four-dimensional (4D) flow magnetic resonance imaging (MRI) before and after ASA and to clarify the association between 4D flow MRI-derived hemodynamic characteristics and the peak pressure gradient (PPG) in patients with drug-refractory HOCM. Methods In this retrospective observational study, 11 patients with HOCM underwent 4D flow MRI before and a week after ASA. The 4D flow MRI included blood flow visualization and quantification using streamline images. The combined score of vortex and helix in AAO was analyzed. The duration and phase count of the AAO vortex or helix flow and the size of the intra-LV anterior vortex were quantified. The correlation between the changes in hemodynamics and the resting PPG at LV outflow tract was also analyzed. We used the paired t-test for the comparison between before and after ASA and the Pearson’s correlation coefficient for the analysis. Results The combined score for the incidence of vortex and/or helix flow in AAO after ASA was significantly lower than that before ASA (1.45 ± 0.52 vs. 1.09 ± 0.30, p = 0.046). The duration (744 ± 291 ms vs. 467 ± 258 ms, p

Abstract In local and global disaster scenes, rapid recognition of victims’ breathing is vital. It is unclear whether the footage transmitted from small drones can enable medical providers to detect breathing. This study investigated the ability of small drones to evaluate breathing correctly after landing on victims’ bodies and hovering over them. We enrolled 46 medical workers in this prospective, randomized, crossover study. The participants were provided with envelopes, from which they were asked to pull four notes sequentially and follow the written instructions (“breathing” and “no breathing”). After they lied on the ground in the supine position, a drone was landed on their abdomen, subsequently hovering over them. Two evaluators were asked to determine whether the participant had followed the “breathing” or “no breathing” instruction based on the real-time footage transmitted from the drone camera. The same experiment was performed while the participant was in the prone position. If both evaluators were able to determine the participant’s breathing status correctly, the results were tagged as “correct.” All experiments were successfully performed. Breathing was correctly determined in all 46 participants (100%) when the drone was landed on the abdomen and in 19 participants when the drone hovered over them while they were in the supine position (p

Background: Atrial fibrillation (AF) ablation is performed under deep sedation, which may cause inspiration-induced negative left atrial pressure (INLAP) associated with deep inspiration. INLAP could be the cause of periprocedural complications. Methods: We retrospectively enrolled 381 patients with AF (mean age, 63.9 ± 10.8 years; 76 women; 216 cases of paroxysmal AF) who underwent CA under deep sedation using an adaptive servo ventilator (ASV). Patients whose LAP was not obtained were excluded. INLAP was defined as 2DS2-Vasc scores (2.3 ± 1.5 vs. 2.1 ± 1.6) and 3% oxygen desaturation indexes (median 18.6 (interquartile range 11.2–31.1) vs. 15.7 (8.1–25.3)), and higher prevalence of diabetes mellitus (23.3 vs. 13.3%) than patients without INLAP. Air embolism occurred in four patients with INLAP (3.0 vs. 0.0%). Conclusion: INLAP is not rare in patients undergoing CA for AF under deep sedation with ASV. Much attention should be paid to the possibility of air embolism in patients with INLAP.

Pulmonary vein isolation has become a cornerstone treatment for catheter ablation of atrial fibrillation (AF). Recent reports show that additional ablation targeting low-voltage zones reduces AF recurrence. However, the pre-procedural predictors of low-voltage zones remain elusive. We retrospectively enrolled 359 patients (mean age 63.7 ± 10.8 years; 73 females; and 149 had persistent atrial fibrillation) who underwent catheter ablation for AF and left atrial (LA) voltage mapping during sinus rhythm or atrial pacing. Low-voltage zones were defined as area of > 5 cm2 with a bipolar electrogram amplitude of < 0.50 mV. Overall, 51 (14.2%) patients had low-voltage zones. Patients with low-voltage zones were older (67.9 ± 9.9 vs. 63.0 ± 10.8 years; P = 0.003), predominantly female (33.3% vs. 18.2%; P = 0.013), had higher prevalence of dilated cardiomyopathy (DCM) (11.8% vs. 1.6%; P = 0.002) and hypertrophic cardiomyopathy (HCM) (9.8% vs. 2.6%; P = 0.025), and had larger LA volumes (153.6 ± 46.4 vs. 117.7 ± 67.8 mL; P < 0.001) than those without low-voltage zones. Multivariate logistic regression analysis revealed that age (OR 1.060; 95% CI 1.022–1.101, P = 0.002), female sex (OR 2.978; 95% CI 1.340–6.615, P = 0.007), DCM (OR 8.341; 95% CI 1.381–50.372, P = 0.021), HCM (OR 5.044; 95% CI 1.314–19.363, P = 0.018), persistent AF (OR 4.188; 95% CI 1.928–9.100, P < 0.001), and larger LA volume (OR 3.215; 95% CI 1.378–7.502, P = 0.007) were independently associated with the presence of low-voltage zones. Patient age, female sex, DCM, HCM, persistent AF and larger LA volume may predict the presence of low-voltage zones and could be useful in selecting the appropriate ablation strategy for AF.

The aim of this study was to assess abatacept in rheumatoid arthritis (RA) patient. Patients (20 men, 89 women, aged 61.9 ± 10.4 y) who responded inadequately to conventional synthetic disease-modifying anti-rheumatic drug were treated with abatacept for 24-months. Disease activity score in 28 joints (DAS28-CRP) was evaluated. Of 109 patients, 82 (75.2%) were on methotrexate (MTX; mean dosage 9.0 ± 2.7 mg/week); 48 (44.0%) were naive to biologics and 61 (56.0%) had failed biologics. The 1- and 2-year retention rates were 77% and 53%, respectively. At 24-months, the DAS28-CRP remission rates were 62.8% in the biologic-naïve patients, and 33.3% in the biologic-failure patients (p

ObjectivesReactive oxygen species generated by xanthine oxidoreductase (XOR) are associated with the progression of atherosclerosis. However, changes in plasma XOR (pXOR) activity after percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) remains unknown.MethodsHerein, we compared the change in the pXOR activity in patients undergoing PCI with that in patients undergoing coronary angiography (CAG) and further evaluated the relation between changes in pXOR activity and in-hospital and long-term outcomes of patients undergoing PCI. The pXOR activity of 80 consecutive patients who underwent PCI and 25 patients who underwent CAG during the hospitalization was analyzed daily. The percentage changes from baseline regulated time interval was evaluated.ResultsWe found that although pXOR activity decreased after PCI, and remained low until discharge, no significant changes were observed in patients undergoing CAG. Furthermore, among the patients undergoing PCI, those who experienced in-hospital adverse events, had a higher percentage of pXOR reduction 3 days after PCI. There was no association between these changes and long-term events.ConclusionsA significant change in pXOR activity was observed in patients undergoing PCI than in patients undergoing CAG, and there seems to be a correlation between the in-hospital outcomes and the percentage reduction from baseline in pXOR activity.

Background Drug-eluting stent-induced vasospastic angina (DES-VSA) has emerged as a novel complication in the modern era of percutaneous coronary intervention (PCI). Although beta blockers (BBs) are generally recommended for coronary heart disease, they may promote incidence of DES-VSA. This study aimed to compare the effects of calcium channel blockers (CCBs) perceived to be protective against DES-VSA and BBs on subsequent coronary events after second-generation drug-eluting stent implantation.Methods In this multicentre prospective, randomised study, 52 patients with coronary artery disease who underwent PCI for a single-vessel lesion with everolimus-eluting stent placement were randomised into post-stenting BB (N=26) and CCB (N=26) groups and followed for 24 months to detect any major cardiovascular events (MACE). A positive result on acetylcholine provocation testing during diagnostic coronary angiography (CAG) at 9 months was the primary endpoint for equivalence. MACE included all-cause death, non-fatal myocardial infarction, unstable angina, cerebrovascular disease or coronary revascularisation for stable coronary artery disease after index PCI.Results At 9 months, 42 patients (80.8%) underwent diagnostic coronary angiography and acetylcholine provocation testing. Among them, seven patients in each group were diagnosed with definite vasospasm (intention-to-treat analysis 26.9% vs 26.9%, risk difference 0 (−0.241, 0.241)). Meanwhile, the secondary endpoint, 24-month MACE, was higher in the CCB group (19.2%) than in the BB group (3.8%) (p=0.01). In detail, coronary revascularisation for stable coronary artery disease was the predominant endpoint that contributed to the greater proportion of MACE in the CCB group (CCB (19.2%) vs BB (3.8%), p=0.03).Conclusions The incidence of acetylcholine-induced coronary artery spasms did not differ between patients receiving BBs or CCBs at 9 months after PCI. However, a higher incidence of 2-year MACE was observed in the CCB group, suggesting the importance of BB administration.Trial registration number This study was registered at the Japanese University Hospital Medical Information Network (UMIN) Clinical Trial Registry (The Prospective Randomized Trial for Optimizing Medical Therapy After Stenting: Calcium-Beta Trial; UMIN000008321, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009536).

Cardiovascular disease, including ischemic heart disease, is a leading cause of death worldwide. Improvement of the secondary prevention of ischemic heart disease is necessary. We established a unique referral system to connect hospitals and outpatient clinics to coordinate care between general practitioners and cardiologists. Here, we evaluated the impact and long-term benefits of our system for ischemic heart disease patients undergoing secondary prevention therapy after percutaneous coronary intervention. This single-center retrospective observational study included 3658 consecutive patients who underwent percutaneous coronary intervention at Shizuoka City Hospital between 2010 and 2019. After percutaneous coronary intervention, patients were considered conventional outpatients (conventional follow-up group) or subjected to our unique referral system (referral system group) at the attending cardiologist's discretion. To audit compliance of the treatment with the latest Japanese guidelines, we adopted a circulation-type referral system, whereby general practitioners needed to refer registered patients at least once a year, even if no cardiac events occurred. Clinical events in each patient were evaluated. Net adverse clinical events were defined as a combination of major adverse cardiac, cerebrovascular, and major bleeding events. There were 2241 and 1417 patients in the conventional follow-up and referral system groups, with mean follow-ups of 1255 and 1548 days and cumulative net adverse clinical event incidences of 27.6% and 21.5%, respectively. Kaplan-Meier analysis showed that the occurrence of net adverse clinical events was significantly lower in the referral system group than in the conventional follow-up group (log-rank: P

Background. Secondary prevention of ischaemic heart disease (IHD) is an important aspect of healthcare. To improve the prognosis of and control risk factors for IHD patients, we created a unique referral system called the Shizuoka IHD patient registry. Methods. From 2009 to 2013, we enrolled 1240 patients; they participated in follow-up until 2018. The risk factor target values were as follows: low-density-lipoprotein cholesterol,

Background. Eltrombopag, a nonpeptide thrombopoietin receptor agonist (TPO-RA), has been reported to be an effective therapy for chronic immune thrombocytopenia (ITP). However, a higher incidence of arterial and venous thromboembolic events was reported after using eltrombopag. Case Presentation. A 67-year-old man, treated with eltrombopag due to chronic ITP, was admitted due to acute coronary syndrome (ACS). Although coronary angiography revealed no occlusion, cardiac magnetic resonance imaging suggested a myocardial infarction in the territory of the left circumflex coronary artery. Three months after the ACS event, the obtuse marginal branches exhibited significant stenosis; hence, a percutaneous coronary intervention (PCI) was performed to implant a zotarolimus-eluting stent under the treatment of a dual antiplatelet therapy. However, stent thrombosis occurred 3 hours after PCI and required three other PCIs during the eltrombopag treatment. Conclusion. We present a case of an ITP patient, who experienced repeated coronary and stent thrombosis during the treatment with eltrombopag. We propose that the risk of ACS and consequent coronary stent thrombosis should be considered before the introduction of eltrombopag.

Objectives. To examine the influence of hydrostatic pressure on fractional flow reserve (FFR) in vivo. Background. Systematic differences in FFR values have been observed previously in the left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA). It has been suggested that as the hydrostatic pressure variations caused by the height differences between the catheter tip (mean aortic pressure (Pa)) and pressure-wire sensor (mean distal intracoronary pressure (Pd)) are small, intracoronary pressure need not be corrected. Methods. Resting Pd/Pa and FFR values in 23 patients (27 lesions) were measured and compared in supine and prone positions. These values were corrected by hydrostatic pressure influenced by height levels and compared. Height differences between Pa and Pd were calculated using coronary computed tomography angiographies. Results. In LAD, resting Pd/Pa and FFR values were significantly higher in the prone position than in the supine position (0.97 ± 0.05 vs 0.89 ± 0.04, P

Background: When a rescuer walks alongside a stretcher and compresses the patient’s chest, the rescuer produces low-quality chest compressions. We hypothesized that a stretcher equipped with wing boards allows for better chest compressions than the conventional method. Methods: In this prospective, randomized, crossover study, we enrolled 45 medical workers and students. They performed hands-on chest compressions to a mannequin on a moving stretcher, while either walking (the walk method) or riding on wings attached to the stretcher (the wing method). The depths of the chest compressions were recorded. The participants’ vital signs were measured before and after the trials. Results: The average compression depth during the wing method (5.40 ± 0.50 cm) was greater than during the walk method (4.85 ± 0.80 cm; p < 0.01). The average compression rates during the two minutes were 215 ± 8 and 217 ± 5 compressions in the walk and wing methods, respectively (p = ns). Changes in blood pressure (14 ± 11 vs. 22 ± 14 mmHg), heart rate (32 ± 13 vs. 58 ± 20 bpm), and modified Borg scale (4 (interquartile range: 2–4) vs. 6 (5–7)) were significantly lower in the wing method cohort compared to the walking cohort (p < 0.01). The rescuer’s size and physique were positively correlated with the chest compression depth during the walk method; however, we found no significant correlation in the wing method. Conclusions: Chest compressions performed on the stretcher while moving using the wing method can produce high-quality chest compressions, especially for rescuers with a smaller size and physique.

BackgroundWhereas composite end points are often used in clinical trials of percutaneous coronary interventions (PCI), the impact of individual components on subsequent survival is incompletely defined. We evaluated the association of subsequent acute coronary syndromes (ACS) and unplanned coronary revascularization post‐PCI with long‐term survival. Methods and ResultsFrom 2009 to 2011, the KiCS‐PCI (Keio interhospital Cardiovascular Studies) consecutively enrolled patients undergoing PCI in 14 Japanese teaching hospitals. We identified patients who experienced ACS or unplanned coronary revascularization following their index PCI and compared subsequent survival during the 2‐year follow‐up period using propensity‐matched cohorts of patients who did and did not experience these events. Cox proportional hazard models were used to assess 2‐year all‐cause mortality. Because unstable angina is less severe than acute myocardial infarction, we also generated a separate propensity‐matched cohort for UA post‐PCI. Among 3348 PCI patients (mean age, 67.5±10.7 years; 79.7% male), 214 (6.4%) experienced a subsequent ACS (168 events [78.5%] were unstable angina), and 198 (5.9%) underwent unplanned revascularization. In the propensity‐matched cohorts, patients with a subsequent ACS admission had an increased risk of mortality as compared with those without (hazard ratio, 4.73; 95% confidence interval=1.35–16.6; P=0.015), whereas those with an unplanned revascularization did not have significantly higher risk (hazard ratio, 2.97; 95% confidence interval=0.57–14.3; P=0.19). Among unstable angina events, no association with mortality was observed (hazard ratio, 1.39; 95% confidence interval=0.48–4.00; P=0.54). ConclusionsIn the KiCS‐PCI registry, the incidence of a subsequent ACS was associated with higher mortality, but this association was less apparent after unplanned coronary revascularization or unstable angina. The prognostic implications of different outcomes in a composite end point should be considered when interpreting the results of clinical trials in PCI.

Statin therapy is regarded as an effective medication to reduce cardiovascular events in patients at higher risk for future incidence of coronary artery disease. However, very few studies have been conducted to examine its implementation in non-Western real-world practice. In this study, we sought to describe statin prescription patterns in relation to patient characteristics in a Japanese multicenter percutaneous coronary intervention (PCI) registry as a foundation for quality improvement. We studied 15,024 patients that were prospectively enrolled in the Japan Cardiovascular Database-Keio interhospital Cardiovascular Study Registry from January 2009 to August 2014. The overall discharge statin non-prescription rate was 15.2%, without significant interhospital (MOR = 1.01) or annual differences (MOR = 1.13) observed. Hierarchical multivariable logistic regression analysis accounting for regional differences revealed that the presence of chronic kidney disease was associated with higher rates of statin non-prescription (OR 1.87, 95% confidence interval, 1.69-2.08, p value

Heart failure (HF) is a rapidly growing global public health problem. Since HF results in high mortality and re-hospitalization, new effective treatments are desired. Although it remains controversial, omega 3 polyunsaturated fatty acids (n-3 PUFAs), such as the eicosapentaenoic acid and docosahexaenoic acid, have been widely recognized to have benefits for HF. In a large-scale clinical trial regarding secondary prevention of HF by n-3 PUFA (GISSI-HF trial), the supplementation of n-3 PUFA significantly reduced cardiovascular mortality and hospitalization. Other small clinical studies proposed that n-3 PUFA potentially suppresses the ventricular remodeling and myocardial fibrosis, which thereby improves the ventricular systolic and diastolic function both in ischemic and non-ischemic HF. Basic investigations have further supported our understanding regarding the cardioprotective mechanisms of n-3 PUFA against HF. In these reports, n-3 PUFA has protected hearts through (1) anti-inflammatory effects, (2) intervention of cardiac energy metabolism, (3) modification of cardiac ion channels, (4) improvement of vascular endothelial response, and (5) modulation of autonomic nervous system activity. To clarify the pros and cons of n-3 PUFA on HF, we summarized recent evidence regarding the beneficial effects of n-3 PUFA on HF both from the clinical and basic studies.

Heart failure (HF) frequently coexists with conditions associated with glucose insufficiency, such as insulin resistance and type 2 diabetes mellitus (T2DM), and patients with T2DM have a significantly high incidence of HF. These two closely related diseases cannot be separated on the basis of their treatment. Some antidiabetic drugs failed to improve cardiac outcomes in T2DM patients, despite lowering glucose levels sufficiently. This may be, at least in part, due to a lack of understanding of cardiac insulin resistance. Basic investigations have revealed the significant contribution of cardiac insulin resistance to the pathogenesis and progression of HF; however, there is no clinical evidence of the definition or treatment of cardiac insulin resistance. Mitochondrial dynamics play an important role in cardiac insulin resistance and HF because they maintain cellular homeostasis through energy production, cell survival, and cell proliferation. The innovation of diagnostic tools and/or treatment targeting mitochondrial dynamics is assumed to improve not only the insulin sensitivity of the myocardium and cardiac metabolism, but also the cardiac contraction function. In this review, we summarized the current knowledge on the correlation between cardiac insulin resistance and progression of HF, and discussed the role of mitochondrial dynamics on the pathogenesis of cardiac insulin resistance and HF. We further discuss the possibility of mitochondria-targeted intervention to improve cardiac metabolism and HF.

Although beneficial effects of non-secreting intracellular renin (ns-renin) against ischemia have been reported, the precise mechanism remains unclear. In this study, we investigated the roles of ns-renin and mitochondrial extracellular signal-related kinase (ERK) 1/2 on mitochondrial permeability transition pore (mPTP) opening during ischemia in diabetes mellitus (DM) hearts. When isolated hearts from Wistar rats (non-DM hearts) and Goto-Kakizaki rats (DM hearts) were subjected to ischemia for 70 min by left anterior descending coronary artery ligation, DM hearts exhibited higher left ventricular (LV) developed pressure and lower LV end-diastolic pressure than non-DM hearts, suggesting ischemic resistance. In addition, DM hearts showed increased intracellular renin (int-renin, including secreting and non-secreting renin) in the ischemic area, and a direct renin inhibitor (DRI; aliskiren) attenuated ischemic resistance in DM hearts. ERK1/2 was significantly phosphorylated after ischemia in both whole cell and mitochondrial fractions in DM hearts. In isolated mitochondria from DM hearts, rat recombinant renin (r-renin) significantly phosphorylated mitochondrial ERK1/2, and hyperpolarized mitochondrial membrane potential (ΔΨm) in a U0126 (an inhibitor of mitogen-activated protein kinases/ERK kinases)-sensitive manner. R-renin also attenuated atractyloside (Atr, an mPTP opener)-induced ΔΨm depolarization and Atr-induced mitochondrial swelling in an U0126-sensitive manner in isolated mitochondria from DM hearts. Furthermore, U0126 attenuated ischemic resistance in DM hearts, whereas it did not alter the hemodynamics in non-DM hearts. Our results suggest that the increased int-renin during ischemia may inhibit mPTP opening through activation of mitochondrial ERK1/2, which may be involved in ischemic resistance in DM hearts.

The clinical features of gender differences in takotsubo cardiomyopathy (TC) remain to be determined. The aim of this study was to evaluate the differences in clinical characteristics of male and female patients with TC.We obtained the clinical information of 368 patients diagnosed with TC (84 male, 284 female) from the Tokyo CCU Network database collected from 1 January 2010 to 31 December 2012; the Network is comprised of 71 cardiovascular centers in the Tokyo (Japan) metropolitan area. We attempted to characterize clinical differences during hospitalization, comparing male and female patients with TC.There were no significant differences in apical ballooning type, median echocardiography ejection fraction, serious ventricular arrhythmias (such as ventricular tachycardia or fibrillation), or cardiovascular death between male and female patients. Male patients were younger than female patients (median age at hospitalization for male patients was 72 years vs. 76 years for female patients; p = 0.040). Prior physical stress was more common in male than female patients (50.0% vs.31.3%; p = 0.002), while emotional stress was more common in female patients (19.0% vs. 31.0%; p = 0.039). Severe pump failure (defined as Killip Class > III) (20.2% vs. 10.6%; p = 0.020) and cardiopulmonary supportive therapies (28.6% vs. 12.7%, p < 0.001) were more common in male than female patients. Multivariate analysis revealed that male gender (odds ratio = 4.32, 95% CI = 1.41-13.6, p = 0.011) was an independent predictor of adverse composite cardiac events, including cardiovascular death, severe pump failure, and serious ventricular arrhythmia.Cardiac complications in our dataset appeared to be more common in male than female patients with TC during their hospitalization. Further investigation is required to clarify the underlying mechanisms responsible for the observed gender differences.

Myocardial perfusion scintigraphy (MPS) plays an important role in the evaluation and quantification of myocardial ischemia, and those with significant ischemia (SI) benefit most from revascularization procedures. This study aimed to identify the clinical factors and anatomical features associated with SI in patients with stable ischemic heart disease (SIHD).Data were analyzed from 4197 SIHD patients undergoing percutaneous coronary intervention (PCI). Ischemia was based on MPS findings prior to PCI, with SI defined as an ischemic region of more than 10% of the total left ventricular area. Logistic regression analysis was performed to identify any clinical factors associated with SI. MPS was used to evaluate 1070 (25.5%) patients pre-procedurally. Patients with a history of heart failure, stroke, or anginal symptoms with Canadian Cardiovascular Society class 2 or more were more likely to have SI (odds ratio [OR] 1.63, p = 0.025, OR: 1.85, p = 0.009, and OR: 1.49, p = 0.003, respectively). When angiographic variables were considered, a proximal left anterior descending artery (pLAD) lesion was the sole factor associated with SI (OR: 1.45, p = 0.012). Importantly, those with SI had more in-hospital complications (p = 0.006), most notably post-PCI infarcts (p = 0.008).Patients' background data, such as stronger anginal symptoms or a pLAD lesion, were associated with SI. Patients with SI must be treated with PCI to improve their long-term prognosis; however, procedure-related complications happen more frequently in SI patients than in non-SI patients. Physicians must give their full attention when performing the PCI procedure in SI patients to minimize their complication rate.

BackgroundCongestive physical findings such as pulmonary rales and third heart sound (S3) are hallmarks of acute heart failure (AHF). However, their role in outcome prediction remains unclear. We sought to investigate the association between congestive physical findings upon admission, steady-state biomarkers at the time of discharge, and long-term outcomes in AHF patients.MethodsWe analyzed the data of 133 consecutive AHF patients with an established diagnosis of ischemic or non-ischemic (dilated or hypertrophic) cardiomyopathy, admitted to a single-center university hospital between 2006 and 2010. The treating physician prospectively recorded major symptoms and congestive physical findings of AHF: paroxysmal nocturnal dyspnea, orthopnea, pulmonary rales, jugular venous distension (JVD), S3, and edema. The primary endpoint was defined as rehospitalization for HF.ResultsMajority (63.9%) of the patients had non-ischemic etiology and, at the time of admission, S3 was seen in 69.9% of the patients, JVD in 54.1%, and pulmonary rales in 43.6%. The mean follow-up period was 726 ± 31 days. Patients with pulmonary rales (p < 0.001) and S3 (p = 0.011) had worse readmission rates than those without these findings; the presence of these findings was also associated with elevated troponin T (TnT) levels at the time of discharge (odds ratio [OR] 2.8; p = 0.02 and OR 2.6; p = 0.05, respectively).ConclusionPulmonary rales and S3 were associated with inferior readmission rates and elevated TnT levels on discharge. The worsening of the readmission rate owing to congestive physical findings may be a consequence of on-going myocardial injury.