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Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. Because this effect is time dependent, we exposed Ogt-Tg mice to IH for 4 weeks (IH4W) in the present study. O-GlcNAcylation was significantly enhanced in Ogt-Tg mice vs. wild-type (WT) mice exposed to normoxia and IH4W. Total O-GlcNAcylation levels were significantly increased in WT and Ogt-Tg mice after IH4W vs. normoxia. After IH4W, Ogt-Tg mice displayed significantly exacerbated signs of cardiac hypertrophy and fibrosis in the right ventricles (RVs) but not the left ventricles (LVs). Echocardiography revealed IH4W-induced right ventricular dysfunction. Phosphorylated GSK-3β levels were increased in Ogt-Tg mice vs. WT mice after IH4W, whereas phosphorylated NF-κB p65 levels were unaffected. Mitophagy, which is associated with cardiac dysfunction, was increased in the RVs of Ogt-Tg mice after IH4W. Furthermore, the levels of phosphorylated dynamin-related protein 1 (p-Drp1) were significantly increased, and the expression of mitofusin-2 (MFN2) was significantly decreased. In human embryonic kidney cells, mitochondrial uncoupler-induced mitochondrial dysfunction was accelerated in Ogt-overexpressing cells. In addition to increasing the levels of phosphorylated Smad2, IH4W promoted cardiac fibrosis in the RVs of Ogt-Tg mice. Thus, augmented O-GlcNAcylation may aggravate IH4W-induced right ventricular dysfunction and remodeling by promoting hypertrophy, mitophagy, and fibrosis via GSK-3β inactivation, an increased p-Drp-1/MFN2 ratio, and Smad2 activation, respectively.

Aims To examine the effects of a 24-month treatment with ipragliflozin on carotid intima-media thickness (IMT) in type 2 diabetes patients. Methods and results In this multicenter, prospective, randomized, open-label, and blinded-endpoint investigator-initiated clinical trial, adults with type 2 diabetes and haemoglobin A1C (HbA1c) of 6.0–10.0% (42–86 mmol/mol) were randomized equally to ipragliflozin (50 mg daily) and non-sodium-glucose cotransporter-2 (SGLT2) inhibitor use of standard-care (control group) for type 2 diabetes and were followed-up to 24 months. The primary endpoint was the change in mean common carotid artery IMT (CCA-IMT) from baseline to 24 months. A total of 482 patients were equally allocated to the ipragliflozin (N = 241) and control (N = 241) groups, and 464 patients (median age 68 years, female 31.7%, median type 2 diabetes duration 8 years, median HbA1c 7.3%) were included in the analyses. For the primary endpoint, the changes in the mean CCA-IMT from baseline to 24 months were 0.0013 [95% confidence interval (CI), −0.0155–0.0182] mm and 0.0015 (95% CI, −0.0155–0.0184) mm in the ipragliflozin and control groups, respectively, with an estimated group difference (ipragliflozin-control) of −0.0001 mm (95% CI, −0.0191–0.0189; P = 0.989). A group difference in HbA1c change at 24 months was also non-significant between the treatment groups [−0.1% (95% CI, −0.2–0.1); P = 0.359]. Conclusion Twenty-four months of ipragliflozin treatment did not affect carotid IMT status in patients with type 2 diabetes recruited in the PROTECT study, relative to the non-SGLT2 inhibitor-use standard care for type 2 diabetes.

The number of patients on maintenance hemodialysis (HD) diagnosed with sarcopenia has been increasing through as individuals age. Recent focus is on the condition termed, "dynapenia," which reduces only muscle function, as opposed to sarcopenia, which reduces both muscle mass and function. However, the association between dynapenia and cardio-cerebrovascular (CV) events in patients undergoing HD is largely unknown. The purpose of this study was to evaluate whether sarcopenia and dynapenia are associated with the onset of CV events in patients undergoing HD. We retrospectively analyzed 342 patients undergoing HD between January and December 2018. Patients who underwent HD thrice per week for 3 months were included in the analysis. We adopted the Asian Working Group on Sarcopenia criteria for the diagnosis of sarcopenia and dynapenia. In this study, 244 patients undergoing HD were enrolled. The prevalence of sarcopenia was 38.5%. Sarcopenia was determined to be an independent contributor to CV events in patients undergoing HD. To investigate the clinical relevance of dynapenia in patients with HD, patients without sarcopenia were further divided into dynapenia and non-dynapenia groups. Among 150 patients without sarcopenia, 46 were diagnosed with dynapenia. In the Kaplan-Meier analysis, the rate of CV events was significantly different among the three groups in a stratified manner, with the highest rate in the sarcopenia group and the lowest rate in the non-sarco-dynapenia group. Both patients with sarcopenia and dynapenia had significantly increased CV events compared to those with non-sarco-dynapenia (HR 8.00; 95% CI 2.73-34.1; p 0.0001 vs. HR 4.85; 95% CI 1.28-23.0; p 0.02). Both sarcopenia and dynapenia resulted in significantly higher CV events than non-sarco-dynapenia in patients undergoing HD. Therefore, clinicians should evaluate muscle function in addition to muscle quantity to estimate CV events in patients undergoing HD.

研究グループは、大腿部の筋肉内脂肪が非虚血性心筋症による心不全の予後に影響を与えることを初めて明らかにしました。本研究成果により、大腿部の筋肉内脂肪を測定することで心不全の予後を推測できる可能性が示されました。皮下脂肪や内臓脂肪以外の脂肪組織のことを異所性脂肪と呼び、主なものとしては心臓周囲脂肪や筋肉内脂肪があります。異所性脂肪の一つである心臓周囲脂肪が狭心症や心筋梗塞といった冠動脈疾患や心房細動を引き起こすとの報告はありましたが、身体の他の部位の異所性脂肪が心不全に与える影響についての報告は今までほとんどありませんでした。大腿部の筋肉内脂肪が糖尿病など生活習慣病の発症に影響を与えているという報告は既にあったため、今回、大腿部の筋肉内脂肪が心不全患者の予後に関係するかを調査しました。本研究グループは、2017年9月から2020年1月に大阪公立大学医学部附属病院で、心機能が低下した心不全の精査目的に入院し冠動脈疾患が否定された連続93例を対象とし、CTで大腿部のスキャンを行い、筋肉量と筋肉内脂肪を測定して筋肉内脂肪比を算出しました。筋肉内脂肪比を中央値で2群に分類し、それぞれの群で心血管死もしくは心血管系の病気による予期しない入院の発生率に差があるか検討を行いました。その結果、筋肉内脂肪比が高い群の方が発生率が高く、筋肉内脂肪比が独立した予後規定因子であることが明らかになりました。, Skeletal muscle atrophy is an independent prognostic predictor for patients with chronic heart failure, and the concept of sarcopenia is drawing attention. Furthermore, the importance of not only muscle mass but also ectopic fat has been pointed out. However, ......

A 70-year-old man with severe interstitial pneumonia attributed to limited cutaneous systemic sclerosis was referred to our institution because of worsening dyspnea. High-resolution computed tomography did not show considerable progression compared with previous images, whereas transthoracic echocardiography showed severe right ventricular dysfunction. Oxygen saturation was decreased to 84% at room air. A blood test showed an increase in the plasma brain natriuretic peptide level (289.4 pg/mL). Right heart catheterization (RHC) showed a remarkably high mean pulmonary arterial pressure (mPAP) of 48 mmHg at room air. A vaso reactivity test using inhaled nitric oxide showed improvement of mPAP, pulmonary vascular resistance (PVR), and partial pressure of arterial oxygen. These findings suggested that the patient responded to pulmonary hypertension (PH)-targeted drugs. We then prescribed tadalafil 10 mg and inhaled iloprost 5 µg six times daily. Three weeks after initiating PH-targeted drugs, RHC indicated hemodynamic improvement similar to hemodynamic changes in the vaso reactivity test (mPAP: 28 mmHg; PVR: 4.2 W.U.). He was discharged with improved symptoms. Inhaled nitric oxide during RHC might be helpful to consider the treatment strategy when patients have PH comorbid systemic sclerosis and severe interstitial lung disease.

BACKGROUND Thickening of Achilles tendon (≥9 mm on radiography) is one of the diagnostic criteria for familial hypercholesterolemia (FH). Since FH is associated with premature coronary artery disease (CAD) including acute coronary syndrome (ACS), measurement of Achilles tendon thickness (ATT) is important for early diagnosis of FH. However, clinical significance of mild thickening of Achilles tendon in non-FH patients with CAD is unclear. The present study investigated the association of ATT with coronary lesion severity in early-onset ACS without clinically diagnosed FH. METHODS From outpatients who had a history of ACS under 60 years old, 76 clinically non-FH subjects (71 men and 5 women; mean age at the onset of ACS, 50.5 years) with maximum ATT of

研究グループは、TAVI施術者に対する基本チェックリストによるフレイルの評価が経カテーテル大動脈弁留置術(TAVI)後3年の総死亡の予測因子として有用であることを明らかにしました。本研究成果により、基本チェックリストがフレイルを簡便かつ客観的に評価し、適切な治療方針の決定に役立つと期待できます。フレイルの指標とTAVIとの関連性はこれまでに報告されていますが、それらの指標は検査を多く要するものや、簡便であっても客観性に欠けるものがあります。今回、本研究グループは、2016年1月から2020年12月に本学医学部附属病院でTAVIを施行した280例を対象とし、従来のフレイルの指標に加えて基本チェックリストによるフレイルの評価を行いました。その結果、基本チェックリストにより算出したフレイルの指標は、従来のフレイルの指標と比較し同等であり、生存時間分析でTAVI後3年の死亡の独立した因子であることが分かりました。また、基本チェックリストの総スコア(25点満点)で3群に分類して解析したところ、フレイル群(13～25点)でTAVI後3年の死亡が有意に高いことが分かりました。, Background: Frailty is a major risk factor for death and disability following transcatheter aortic valve implantation (TAVI). The Kihon checklist (KCL) is a simple self-reporting yes/no survey consisting of 25 questions and is used as a screening tool to identify frailty in the primary care setting. No clinical studies have focused on frailty calculated by the KCL in the TAVI cohort. We investigated the 3-year prognostic impact of frailty evaluated by the KCL in patients who underwent TAVI. ......

研究グループは、運動を行った際に酸化ストレスが増加する心不全患者が、予後不良となることを明らかにしました。慢性心不全患者は超高齢化社会において、急激に増加しており、現在は「心不全パンデミック」とも呼ばれています。しかし、治療は対症療法が中心で、病気の進展を防ぐことができないため、高い再入院率・死亡率が社会的に問題となっています。これまで心不全患者の予後改善には有酸素運動が有効とされていましたが、適切な運動量や運動方法はまだ定められていません。本研究では、2013年7月から2015年3月に大阪市立大学医学部附属病院に入院した94人の心不全患者を対象に、運動に伴う酸化ストレスの増減が心不全の予後に与える影響を検討しました。その結果、心肺運動負荷実験で、酸化ストレスが上昇した心不全患者の予後は不良であることが明らかになりました。この結果から、心不全患者の適切な運動量は、運動時の酸化ストレスの変化を評価することで決定できる可能性があることを示唆します。, Aims: Oxidative stress plays an important role in the development and progression of heart failure (HF). Although exercise and oxidative stress are closely related, the effect of acute exercise on reactive oxygen species production and the fluctuation on prognosis are unclear....

The present study investigated the clinical value of myocardial contrast-delayed enhancement (DE) with multidetector computed tomography (MDCT) without iodine re-injection immediately after primary percutaneous coronary intervention (PCI) for predicting future cardiovascular events after acute myocardial infarction (AMI). We performed a prospective study in which 263 consecutive patients with first AMI successfully treated with primary PCI were enrolled. Sixty-four-slice MDCT without the re-injection of contrast medium was performed immediately after PCI. Myocardial DE was considered to be transmural when involving myocardial thickness ≥ 75% (Group A; n = 104), subendocardial (

Background Subcutaneous implantable cardioverter–defibrillator (S-ICD) represents an efficient alternative to transvenous ICD in patients who do not require pacing. The intraoperative defibrillation test (DFT) is recommended during S-ICD implantation to confirm appropriate sensing and successful 65-J termination of induced ventricular fibrillation (VF). However, few cases of oversensing of noise inhibiting therapies have been reported. Case summary We report the case of a 50-year-old man who underwent S-ICD implantation for secondary prevention of sudden cardiac death. Immediately after S-ICD implantation, VF was induced using a 50-Hz burst; however, shock was not delivered owing to sustained noise on the electrogram in the primary vector. Therefore, an external rescue shock was needed at 150 J. We changed the sensing vector from primary to secondary and performed a second DFT. The S-ICD could deliver an appropriate shock and was able to successfully terminate VF without noise markers in the secondary vector. During the second DFT, one back-up pacing was delivered after the shock; the sensing vector then automatically switched from the secondary to the alternate vector. However, noise was observed in the alternate vector despite sinus rhythm restoration. Discussion The present case demonstrated that noise was recorded in two different vectors during DFT, possibly supporting the hypothesis that the muscle spasm of the diaphragm induced by the 50-Hz burst causes oversensing of noise by the S-ICD.

Eicosapentaenoic acid (EPA) has been reported to reduce cardiovascular risk in patients with hypertriglyceridemia. Although several mechanisms underlying the effects of EPA have been demonstrated, those responsible for its beneficial role in patients with hypertriglyceridemia without evidence of coronary artery disease (CAD) have not been fully elucidated. We sought to clarify the main factors associated with EPA administration that led to improved endothelial function.Forty-seven consecutive patients with mild hypertriglyceridemia (mean age, 59 ± 13 years) without evidence of CAD were prospectively enrolled and administered purified EPA (1800 mg/day). Forty-four patients who were not administered EPA were enrolled as age- and sex-matched controls. Clinical variables and flow-mediated dilation (FMD) were examined before and after 6 months of treatment. Univariate and multivariate regression analyses were performed between FMD changes and clinical variables.EPA treatment decreased triglyceride levels (from 224.6 ± 58.8 to 151.8 ± 54.5 mg/dl, p 0.001) and increased FMD (from 4.21% ± 1.91% to 6.21% ± 2.30%, p 0.001). Multivariate analysis showed that the change in FMD was associated with the baseline high-density lipoprotein cholesterol (HDL-C) level (β = -0.331, p = 0.027) and the change in EPA/arachidonic acid (AA) ratio (β = 0.301, p = 0.048).EPA treatment improved triglyceride levels and FMD in patients with mild hypertriglyceridemia and without evidence of CAD. The baseline HDL-C level and the change in EPA/AA ratio predicted FMD improvement. The beneficial effects of EPA on triglyceride-rich lipoproteins and vascular endothelium may help improve endothelial function.

Subcutaneous implantable cardioverter-defibrillator implantation is known to be a safe procedure. However, inappropriate lead insertion can lead to serious complications. We present a case where an inappropriate lead placement resulted in puncturing the lung parenchyma, and successful management of the lead-related pneumothorax through thoracoscopic lead removal and partial lung resection. (Level of Difficulty: Intermediate.), Graphical abstract, Subcutaneous implantable cardioverter-defibrillator implantation is known to be a safe procedure. However, inappropriate lead insertion can lead to serious…

The blood levels of atrial and brain natriuretic peptides (ANP and BNP) are both increased markedly in hemodialysis patients, but the kinetics of the two are not always parallel. The present study investigated the association of changes in ANP and BNP levels before and after dialysis with changes in cardiac function in hemodialysis patients. A total of 57 patients (mean age 64 years, 47 males and 10 females) on maintenance hemodialysis with sinus rhythm were enrolled. Blood samples were taken at the beginning and end of dialysis, and plasma levels of ANP and BNP were measured. Changes in cardiac function during dialysis were examined by echocardiography performed just before and after dialysis. Both plasma ANP and BNP concentrations decreased significantly after hemodialysis, but the rate of decrease in BNP [mean ± SD, 555 ± 503 to 519 ± 477 pg/mL (- 6.4%), P = 0.011] was much smaller than that in ANP [233 ± 123 to 132 ± 83 pg/mL (- 43.4%), P 0.001]. As for the relation to the changes in echocardiographic parameters before and after dialysis, the decrease in inferior vena cava diameter had a close correlation with the decrease in ANP (r = 0.528, P 0.001), but not BNP. In contrast, the decrease in left ventricular end-diastolic volume index was correlated only with the decrease in BNP (r = 0.297, P = 0.035). The peak velocity ratio of early diastolic to atrial filling decreased with preload reduction by dialysis, and its decrease was more strongly correlated with the decrease in BNP (r = 0.407, P = 0.002) than that in ANP (r = 0.273, P = 0.040). These results demonstrated that in hemodialysis patients, the decrease in plasma ANP by a single dialysis was essentially caused by blood volume reduction, while BNP decrease was mainly induced by the reduction of left ventricular overload. Our findings indicate that the kinetics of both peptides during dialysis are regulated by different cardiac and hemodynamic factors.

研究グループは、血管内視鏡で大腿膝窩動脈に観察される潰瘍性プラークで生じる血栓が膝下動脈の塞栓源であることを初めて明らかにしました。本研究成果は、下肢閉塞性動脈硬化症に適した薬物療法の決定に寄与できると期待されます。下肢閉塞性動脈硬化症の患者において、膝下動脈の閉塞狭窄病変の程度は予後と相関する重要な因子として知られています。近年の病理学的研究から上流からの血栓による塞栓が膝下動脈病変の形成機序の一つとして想定されていますが、血栓が生体内のどこで生じているのか未だ同定されていませんでした。そこで、本研究グループは、医学部附属病院の循環器内科において大腿膝窩動脈に対して経皮的下肢動脈形成術を施行した連続症例研究31例を対象とし、手技開始前に血管内視鏡を用いて膝下動脈の上流血管である大腿膝窩動脈を観察しました。その結果、血管内視鏡で潰瘍性プラークが観察された23人(74.2%)の患者のうち22人(95.7%)に血管壁に血栓像が観察され、これは潰瘍性プラークが観察されなかった群より高く(37.5%)、また、潰瘍性プラークは膝下動脈の閉塞狭窄の程度を示す指標(Angiographic runoff score)とも強い相関があることがわかりました。, Purpose: The aim of this study was to validate a hypothesis that there is a correlation between up-stream atherosclerosis in femoropopliteal arteries (FPA) assessed by angioscopy and poor angiographic runoff score (ARS). ……

Cholesterol crystals (CCs) are frequently found in high-risk plaques, such as thin-capped fibroatheromas. The purpose of this study was to investigate the associations of CCs, plaque morphologies, and post-stent optical frequency domain imaging (OFDI) findings with periprocedural cardiac troponin (cTn) elevation in patients treated with percutaneous coronary intervention (PCI). This study consists of 119 patients with stable coronary artery disease (CAD) with normal cTn levels who underwent OFDI-guided PCI. Periprocedural cTn elevation was defined as an elevation of cTn ≥ × 5 times the upper reference limit after PCI. Pre- and post-stent OFDI findings, including fibrous cap thickness (FCT), presence of CCs, and parameters for lipid and calcification were analyzed. A total of 37 (31%) patients were classified into the periprocedural cTn elevation group. Compared with lesions without CCs, lesions exhibiting CCs had thinner FCT, larger lipid arc, and longer lipid length, and were more likely to have irregular protrusion and in-stent thrombus (all p

INTRODUCTION The electrocardiograms (ECG) criteria to anchor the lead to the right ventricular septum have not been established. This study aimed to identify ECG criteria of pacing at the right ventricular mid septum (RVMS) and investigate whether the paced QRS duration (pQRSd) from the RVMS was narrow. METHODS AND RESULTS In 42 patients, ECG pacing at the basal anterior wall (BA), mid-anterior wall (MA), apex (AP), and mid septum (MS) was recorded. The pacing sites were validated by using right ventriculography and computed tomography. We estimated the ECG parameters and compared them among the four pacing sites. The combination of simple four paced-ECG parameters could reliably confirm the pacing at the RVMS. The area under the receiver-operating characteristics curve for the number of positive findings among the following: (a) positive QRS in lead aVL, (b) QRS notching in lead I, (c) precordial leads transition at less than V5, and (d) presence of isoelectric QRS in the inferior leads was 0.95 (95% confidence interval, 0.91-0.98) and the number of positive findings (≥3) had a sensitivity of 83.3% and a specificity of 93.7% for discriminating MS from the other sites. The pQRSd with three or more positive findings was significantly narrower than that with less than three positive findings (≥3: 137.4 ± 9.2 ms

Type 2 diabetes mellitus (T2DM) has been reported to be associated with cardiac remodeling. Although O-GlcNAcylation is known to be elevated in diabetic and ischemic hearts, the effects of O-GlcNAcylation on cardiac remodeling induced by intermittent hypoxia (IH), such as sleep apnea syndrome (SAS), remain unknown. To evaluate the effects, we induced IH in wild-type (WT) and transgenic O-GlcNAc transferase (Ogt-Tg) mice. Two weeks of IH increased O-GlcNAcylation in the heart tissues of both strains of mice, whereas O-GlcNAcylation in Ogt-Tg mice was significantly higher than that in WT mice under both normoxic and IH conditions. WT mice exhibited cardiac remodeling after IH, whereas cardiac remodeling was significantly attenuated in Ogt-Tg mice. Oxidative stress and apoptosis increased after IH in both strains of mice, whereas the rate of increase in these processes in Ogt-Tg mice was significantly lower than that in WT mice. To examine the mechanism of cardiac remodeling attenuation in Ogt-Tg mice after IH, the effects of O-GlcNAcylation on the activities of the master regulators nuclear factor of activated T cells (NFAT) and NF-κB were determined. The O-GlcNAcylation of GSK-3β, a negative regulator of NFAT, was significantly increased in Ogt-Tg mice, whereas the phosphorylation of GSK-3β was reciprocally reduced. The same result was observed for NF-κB p65. An in vitro reporter assay showed that the augmentation of O-GlcNAcylation by an O-GlcNAcase inhibitor suppressed NFAT and NF-κB promoter activity. These data suggest that augmented O-GlcNAcylation mitigates IH-induced cardiac remodeling by suppressing NFAT and NF-κB activities through the O-GlcNAcylation of GSK-3β and NF-κB p65.

BACKGROUND The implantation of leads in the right atrial septum (RAS) or the right ventricular septum (RVS) is technically challenging, and dislodgement occurs occasionally. This study aims to determine a predictor for the dislodgement of leads implanted in the RAS or RVS. METHODS This retrospective cohort study enrolled 137 consecutive patients who underwent the cardiac implantable electronic devices implantation, using active fixation leads in the RAS and RVS. We compared the pacing threshold, R- or P-wave amplitude, slew rate, and presence of the current of injury (COI) between dislodged and nondislodged leads. RESULTS We performed lead fixation for 74 and 125 times in the RAS and RVS, respectively. Atrial lead dislodgement occurred five times (6.8%) intraoperatively and five times (6.8%) postoperatively, whereas ventricular lead dislodgement occurred eight times (6.4%) intraoperatively and three times (2.4%) postoperatively. Although there were no lead parameters that showed a significant difference common to RAS lead and RVS lead, the presence of the COI was significantly different between nondislodged and dislodged leads in both the RAS and RVS (atrial leads: 57.8% vs 0%, P

Background Although careful monitoring of asymptomatic severe aortic stenosis (AS) is recommended to prevent missing the optimal timing of surgical or transcatheter aortic valve replacement, prophylactic treatment that could extend the asymptomatic period remains unknown. In a hypertensive population, high blood pressure (BP) measured at the doctor's office is known to be associated with B-type natriuretic peptide (BNP) level, a surrogate marker for symptomatic deterioration in AS. Little is known regarding the association between nocturnal BP variables and BNP in severe AS with preserved ejection fraction (EF). Methods and Results: The subjects consisted of 78 severe AS patients (mean age, 79±6 years) with preserved EF. Nocturnal BP was measured hourly using a home BP monitoring device. On multiple regression analysis, nocturnal mean systolic BP (SBP) remained independently associated with BNP after adjustment for age, sex, body mass index, estimated glomerular filtration rate, antihypertensive medication class, early diastolic mitral annular velocity, and left ventricular mass index (P=0.03), whereas diastolic BP (DBP) and variables of BP variability were not. Conclusions Higher nocturnal SBP rather than DBP or indices of BP variability was independently associated with BNP in AS patients with preserved EF. Intervention for nocturnal SBP may therefore extend the asymptomatic period and improve prognosis.

Background: Tolvaptan is a vasopressin type 2 receptor antagonist used in heart failure (HF) with refractory diuretic resistance. However, since tolvaptan is also ineffective in some HF patients with reduced ejection fraction (HFrEF), the identification of responders is important. Methods: The study population consisted of 51 HFrEF patients who were administered tolvaptan (EF, 28 ± 7%). We defined responders as patients with a ≥50% increase in urine volume during the 24-hours after administration of tolvaptan. All patients underwent comprehensive transthoracic echocardiography before administration of tolvaptan. Patients were followed for 120 days to ascertain secondary events (cardiac death and rehospitalization for HF). Results: Multiple regression analysis indicated that right ventricular (RV) enlargement (defined as basal RV diameter > 41 mm and midlevel RV diameter > 35 mm, according to guidelines) remained a predictor of response after adjustment for age, sex, starting dosage of tolvaptan, and estimated glomerular filtration rate (odds ratio, 4.88; 95%-confidence interval, 1.26–18.9; P

Aim: Neopterin is an activation marker for monocytes/macrophages. We prospectively investigated the predictive value of plasma neopterin levels on 2-year and long-term cardiovascular events in patients with stable angina pectoris (SAP) undergoing coronary stent implantation. Methods: We studied 123 consecutive patients with SAP who underwent primary coronary stenting (44 patients with bare metal stent: BMS group and 79 with drug-eluting stent: DES group). Plasma neopterin levels were measured on admission using HPLC. Moreover, one frozen coronary artery specimen after DES and three frozen coronary specimens after BMS were obtained by autopsy or endarterectomy, followed by immunohistochemical staining for neopterin. Results: Plasma neopterin levels were significantly higher in patients with cardiovascular events than in those without them (P < 0.001). In subgroup analyses, higher levels of plasma neopterin in patients with cardiovascular events (P < 0.001) and a positive correlation between neopterin levels and late lumen loss after stenting (P = 0.008) were observed in the BMS group but not in the DES group (P = 0.53 and P = 0.17, respectively). In long-term cardiovascular events, multivariate Cox regression analysis identified the significance of the high-neopterin group as independent determinants of cardiovascular events (hazard ratio, 2.225; 95% CI, 1.283–3.857; P = 0.004). Immunohistochemical staining showed abundant neopterin-positive macrophages in the neointima after BMS implantation but no neopterin-positive macrophages in the neointima after DES implantation. Conclusion: These findings suggest that neopterin is associated with cardiovascular events after coronary stent implantation in patients with SAP. However, there might be a strong association between neopterin and cardiovascular events after BMS but not after DES in these patients.

Background: We hypothesized that the post-operative aorto-mitral angle might relate to the occurrence of post-operative atrial arrhythmia (AA), including atrial fibrillation and atrial tachycardia, after mitral valve repair in patients with mitral regurgitation (MR). The purpose of the present study was to determine the effects of the post-operative aorto-mitral angle on new onset AA after mitral valve repair with mitral annuloplasty for treating MR. Methods: One-hundred seventy-two patients without any history of AA underwent mitral valve repair with mitral annuloplasty in our institution between 2008 and 2017. Patient information, including medical records and echocardiographic data, were retrospectively studied. Results: AA occurred in 15 (8.7%) patients during the follow-up period (median, 35.7 months; range, 0.5-132 months). The patients with AA had a longer cardiopulmonary bypass time and a smaller aorto-mitral angle at post-operative TTE than the others (119 ± 6 degrees vs. 125 ± 10 degrees, P = 0.003). There was no significant difference in the degree of post-operative residual MR or functional MS between the groups. In a multivariate Cox proportional hazards analysis, the longer cardiopulmonary bypass time and the smaller post-operative aorto-mitral angle were independent predictors of the occurrence of AA during the follow-up period (odds ratio per 10 minutes 1.11; 95% CI 1.02-1.22, P = 0.019: odds ratio 0.91; 95% CI 0.85-0.98, P = 0.012). Conclusion: A small aorto-mitral angle at post-operative TTE was a predictor of new onset AA after a mitral valve repair for treating MR.

Protective effects of tolvaptan against worsening renal function in acute heart failure have been shown. However, long-term effects of its agent on renal function remain to be elucidated. The present study investigated retrospectively whether long-term treatment with tolvaptan exerts renoprotective effects in patients with chronic heart failure, by comparing serial changes in estimated glomerular filtration rate (eGFR) for years before and after tolvaptan administration. From 63 outpatients with chronic heart failure taking diuretics including tolvaptan, 34 patients whose eGFR levels were continuously measured for more than 6 months both before and after administration of tolvaptan (average dose, 7.8 mg/day at the end of the follow-up period) were selected as eligible for the present analyses. All eGFR values were separately plotted before and after the initiation of treatment with tolvaptan (except hospitalization periods) along the time course axis and the slope of the linear regression curve was calculated as an annual change in eGFR. The mean follow-up periods before and after tolvaptan administration were 1197 and 784 days (3.3 and 2.1 years), respectively. Changing rates of eGFR per year were significantly ameliorated after treatment with tolvaptan (mean ± SD, − 8.02 ± 9.35 to − 1.62 ± 5.09 mL/min/1.73m2 /year, P = 0.001). In echocardiographic parameters, inferior vena cava (IVC) diameter significantly decreased after tolvaptan administration, and the decrease in IVC diameter was correlated with the improvement of eGFR decline slope after administration of tolvaptan (P = 0.0075). This longitudinal observational study indicated that long-term treatment with tolvaptan ameliorated annual decline in eGFR in outpatients with chronic heart failure. Our findings suggest that tolvaptan has a protective effect against chronically worsening renal function in heart failure patients.

AimsAcute decompensated heart failure (ADHF) can occur early after transcatheter aortic valve implantation (TAVI), but the risk factors or mechanisms associated with it have not been fully determined. This hypothesis-generating study aimed to investigate the clinical indices associated with the development of ADHF within 72 hours after TAVI and to improve procedural approaches for TAVI.Method and resultsIn this single-centre hypothesis generating prospective observational study, we enrolled 156 consecutive patients with severe aortic stenosis who underwent TAVI between January 2016 and February 2018 at our institution. We set the primary endpoint as the new development of ADHF within 72 hours after TAVI, and clinical indices associated with it were evaluated using a multivariable logistic model. The median age of the patients was 83 (quartile range 80–86) years, 48 (30.8%) were men and the median Society of Thoracic Surgery-Predicted Risk of Mortality was 7.1 (range 5.2–10.4). Mitral stenosis (MS), defined as mean transmitral valve pressure gradient ≥5 mm Hg, was present in 15 (9.6%) patients. After TAVI, the invasive mean transaortic valve pressure gradient (mAVPG) decreased from 48 (36–66) to 7 (5–11) mm Hg, and 12 (7.7%) patients developed ADHF within 72 hours after TAVI. Multivariable logistic regression analysis showed that MS (adjusted OR, 14.227; 95% CI 2.654 to 86.698; p=0.002) and greater decreases in mAVPG (1.038; 1.003 to 1.080; p=0.044) were associated with ADHF.ConclusionsMS and drastic improvement of mAVPG were associated with new development of ADHF within 72 hours after TAVI.

Background Skeletal muscle atrophy is an independent prognostic predictor for patients with chronic heart failure, and the concept of sarcopenia is drawing attention. Furthermore, the importance of not only muscle mass but also intramuscular fat (IMF) has been pointed out. However, there is a lack of consensus on the implications of ectopic fat for the prognosis in patients with non-ischemic cardiomyopathy. Purpose We investigated whether ectopic fat in the thigh affects the prognosis with non-ischemic cardiomyopathy. Methods We recruited 105 patients who were diagnosed with non-ischemic cardiomyopathy by cardiac catheterization and echocardiographic date between September 2017 and November 2019. Finally 73 patients with reduced EF (EF 40% or less) enrolled in this prospective study. Functional status was evaluated by using cardiopulmonary exercise test at baseline. All patients were measured quantity of epicardial fat and thigh IMF percentage (%IMF) using computed tomography scan. Demographic, laboratory and echocardiographic date were collected from the patients' medical records. Clinical endpoints were unexpected readmission. Results During the follow-up period 18 patients had adverse events. The %IMF was significantly higher in the group with adverse events than without (5.57±5.70 and 3.02±2.44%, respectively; p Conclusions In non-ischemic cardiomyopathy patients with reduced EF, %IMF may have important adverse consequences such as increased cardiac-related events. Kaplan-Meier curves Funding Acknowledgement Type of funding source: None

Background Atherosclerotic cardiovascular disease including acute myocardial infarction (AMI) has become one of major co-existing diseases in cancer patients due to their improved survival rate. Current guideline recommends dual-antiplatelet therapy (DAPT) in patients with AMI. Given that the presence of cancer elevates not only coagulability but bleeding risks, these substrate may further worsen cardiovascular outcomes and bleeding risks in cancer subjects with AMI receiving DAPT. Methods We retrospectively analyzed 712 AMI patients treated by primary PCI with drug-eluting stent and DAPT between 2007 and 2017. The diagnosis of cancer was determined through medical record review. Clinical characteristics, thromboembolic (=all-cause death+non-fatal MI+stroke) and bleeding events were compared in AMI subjects with vs. without cancer. Results Cancer was identified in 11.1% (=79/712) of study subjects. Of these, around 40% of them had gastrointestinal cancer (=35/79), followed by lung cancer (=5/79) and breast cancer (=8/79). Cancer patients were more likely to be older (77±7 v. 69±13 years, p Conclusions Under the use of guideline recommended DAPT, the concomitance of cancer in AMI subjects was a predictor for thromboembolic as well as bleeding events. In particular, the relationship between cancer and bleeding was significant. These observations underscore the appropriate selection and duration of anti-thrombotic agents in AMI subjects with cancer. Cardiac/Bleeding Events in AMI Subjects Funding Acknowledgement Type of funding source: None

Background Smoking predisposes individuals to endothelial dysfunction. Both flow-mediated dilation (FMD) and reactive hyperemia peripheral artery tonometry (RH-PAT) are used to assess endothelial function. However, there are differences in the physiology of vascular beds being tested and in the response of conduit and resistive vessels to RH. Therefore, whether smoking cessation demonstrates comparable effects on endothelial function evaluated by FMD and by RH-PAT remains unclear. Purpose We aimed to evaluate the effects of smoking cessation on endothelial function evaluated simultaneously by FMD and RH-PAT. Methods Thirty-eight consecutive current smokers (mean±standard deviation; age, 65±10 years) who visited our smoking cessation outpatient department and succeeded in smoking cessation with varenicline were enrolled. Clinical variables, FMD, and natural logarithmic transformation of the reactive hyperemia index (Ln-RHI) were examined before and 20 weeks after treatment initiation. Fifteen current smokers who failed in smoking cessation were enrolled as age- and sex-matched controls. The Spearman's rank correlation coefficient and intraclass correlation coefficient (ICC) for a two-way mixed effects model were performed to assess the agreement of changes in FMD and Ln-RHI. Multivariate logistic regression analysis was performed to examine the associations between the presence of increase in FMD or Ln-RHI and clinical variables. Results FMD significantly improved after smoking cessation (3.42%±1.96% to 4.45%±2.28%; p=0.019), whereas Ln-RHI did not (0.53±0.25 to 0.59±0.21; p=0.223). The Spearman's rank correlation coefficient between changes in FMD and Ln-RHI was −0.013, and the ICC was −0.002 (p=0.506). In the multivariate logistic regression analysis, an increase in FMD or Ln-RHI was predicted based on the baseline FMD (odds ratio = 0.54, p=0.013) or Ln-RHI (odds ratio = 0.36, p=0.012), respectively, after adjusting for age and sex. Conclusions There was significant improvement in the endothelial function assessed by FMD, but not by Ln-RHI, after smoking cessation. In addition, there was disagreement between changes in FMD and those in Ln-RHI. Smoking cessation may have varying effects on the endothelial function of the conduit and digital vessels. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grant-in-aid for scientific research from the ministry of education, science and culture of Japan

Background Epicardial adipose tissue (EAT) has been recognized to contribute inflammatory activity and atherosclerosis. On the other hand, it has been reported that the volume of EAT is lower in non-ischemic heart failure (HF) patients than healthy individuals. However, the difference in regional muscle-adipose distribution including EAT between HF with preserved ejection fraction (HFpEF) and HF reduced ejection fraction (HFrEF) has not been investigated. In addition, we investigated whether distribution of body composition contributed to exercise capacity. Methods The study included 105 non-ischemic HF patients diagnosed by cardiac catheterization between September 2017 and November 2019. Epicardial, abdominal and thigh muscle and adipose tissue volume were measured by computed tomography (CT), and exercise tolerance was evaluated by symptom-limited cardiopulmonary exercise test. Results Patients were divided into 2 groups according to the left ventricular ejection fraction, ≥40% as HFpEF (n=28) or Conclusion In patient with nonischemic HF, the pattern of regional adipose distribution may have important role in pathologically. HFpEF and HFrEF has different pattern despite similar body mass index. These differences may be related to impaired exercise tolerance in these 2 different types of HF. Correlation between EAT and AT, peak VO2 Funding Acknowledgement Type of funding source: None

Smoking predisposes individuals to endothelial dysfunction. Flow-mediated dilation (FMD) and reactive hyperemia peripheral artery tonometry (RH-PAT) are used to assess endothelial function. However, whether smoking cessation demonstrates comparable effects on endothelial function evaluated by FMD and RH-PAT remains unclear. Thus, we aimed to evaluate the effects of smoking cessation on endothelial function evaluated simultaneously by FMD and RH-PAT and clarify the factors associated with these effects. Fifty-eight consecutive current smokers (mean ± standard deviation; age, 64 ± 11 years) who visited our smoking cessation outpatient department and succeeded with smoking cessation were enrolled. Twenty-one continued smokers were enrolled as age- and sex-matched controls. Clinical variables, FMD, and natural logarithmic transformation of the reactive hyperemia index (Ln-RHI) were examined before and 20 weeks after treatment initiation. In 58 smokers who succeeded with smoking cessation, FMD significantly improved (3.80 ± 2.24 to 4.60 ± 2.55%; p = 0.013), whereas Ln-RHI did not (0.59 ± 0.28 to 0.66 ± 0.22; p = 0.092). Spearman’s rank correlation coefficient between changes in FMD and Ln-RHI was −0.004, and the intraclass correlation coefficient for a two-way mixed effects model was

Background Recently, there are some reports that hypo-attenuated leaflet thickening (HALT) following transcatheter aortic valve implantation (TAVI) is incidentally detected by multi-slice computed tomography. It is believed that valve thrombosis causes HALT, because oral anticoagulation therapy (OAC) is effective for HALT regression. Furthermore, it is reported that d-dimer level increases in patients with HALT, and might be a key biomarker to detect HALT. Purpose We sought to investigate the predictors related to increased d-dimer level at 6 months after follow-up TAVI. Methods We enrolled 124 consecutive patients who underwent successful TAVI between 2016 and 2018. Study patients were classified into two groups according to antithrombotic therapy resume (OAC therapy or anti-platelet therapy).We set the primary endpoint as the d-dimer levels at 6 months after TAVI. To evaluate the risks of the primary endpoint, we employed a multivariable linear regression model, setting the primary endpoint as an objective variable and patient and clinical backgrounds as explanatory variables. Furthermore, we set the secondary endpoint as one-year bleeding event. Results The median age of patients was 83 years old (quartile 80-87). Patients who had taken OAC at 6 months follow-up after TAVI were 29.8%. The median d-dimer level at 6 months after TAVI was 1.3 (1.0-2.2) µg/ml, and OAC group had statistically lower d-dimer level at 6 months follow-up than those in non-OAC group (p = 0.020). Uni-variable liner regression model demonstrated that increased d-dimer level at follow-up had significant relationship with large effective orifice area (EOA) (p = 0.002) and low left ventricular ejection fraction (LVEF) (p = 0.048) after TAVI. Furthermore, large EOA (p = 0.003) and OAC therapy (p = 0.027) were independently associated with increased d-dimer level in multivariate analysis. Kaplan-Meier estimates revealed that there were no significant difference regarding one-year bleeding event between OAC group and non-OAC group (long-rank p = 0.167). Conclusions This study suggests that large EOA after TAVI is associated with increased d-dimer levels at 6 months after TAVI, and OAC therapy might have a potential to decrease d-dimer level after TAVI without increase of bleeding events. Abstract P107 Figure: One-year bleeding event

Dual antiplatelet therapy (DAPT) with thienopyridine and aspirin is the standard care for the prevention of stent thrombosis. However, the optimal duration and effect of the duration of DAPT on intra-stent thrombus (IS-Th) formation are unknown. The NIPPON study (Nobori Dual Antiplatelet Therapy as Appropriate Duration) was an open label, randomized multicenter, assessor-blinded, trial designed to demonstrate the non-inferiority of shorter (6-month) DAPT to prolonged (18-month) DAPT, after biolimus A9 eluting stent implantation in 3773 patients at 130 sites in Japan. Among them, 101 patients were randomly allocated for an optical coherence tomography (OCT) sub-study to assess the difference of local IS-Th formation between the two groups. In addition to standard OCT parameters, the number of IS-Th formed was counted in each target stent at 8 months. Baseline patient characteristics were not different between the 6- and 18-month groups. IS-Th was detected in 9.8% of the cases and the presence of IS-Th was not significantly different between the two groups (10.9% in 6-month vs. 9.1% in 12-month, P = 0.76). Furthermore, the number of IS-Th formed was not significantly different between the two groups. This OCT sub-study was in line with the main NIPPON study which demonstrated the non-inferiority of 6-month DAPT to 18-month DAPT. Shorter DAPT duration did not promote progressive IS-Th formation at the mid-term time point. Electronic supplementary material The online version of this article (10.1007/s00380-018-1131-7) contains supplementary material, which is available to authorized users.

Background: Left atrial (LA) dilatation in patients with atrial fibrillation (AF) can induce functional mitral regurgitation (MR) despite a preserved left ventricular ejection fraction (LVEF). The purpose of this study was to investigate the etiology of this functional MR. Methods: We retrospectively examined clinical and echocardiographic data from 5,202 consecutive cases that underwent transthoracic echocardiography. AF appeared in 544 patients, and we selected 159 with AF and LVEF ≥50% after excluding patients with other underlying heart diseases. Results: Significant (moderate or greater) degrees of functional MR were seen in 13 (8.2%) patients and were more frequently seen in patients with an AF duration of >10 years than in others (27 vs. 4%, p = 0.0057). Multiple regression analysis revealed that both the LA dimension index and the left ventricular (LV) systolic dimension index were independent determinants of the MR grading. Among the mitral morphologic parameters, the mitral annular (MA) dimension index and the hamstringing phenomenon of the posterior mitral leaflet were independent determinants of MR grading. Significant MR was not seen in patients without LA dilatations, but it occurred in 14% of patients with LA dilatation alone and in 55% with both LA and LV dilatations; the MA dimension index increased in this order. Conclusions: The grading of functional MR occurring in patients with AF and preserved LVEF depends on both the LA dimension and the LV systolic dimension. The MR grading also depends on both the MA dilatation and the hamstringing phenomenon of the posterior mitral leaflet.

Background Little evidence is available regarding the risk of peri-procedural stroke detected by diffusion-weighted magnetic resonance imaging (DW-MRI) after transcatheter aortic valve implantation (TAVI). Our purpose was to evaluate stroke risk after TAVI using DW-MRI by enrolling consecutive patients who underwent transfemoral TAVI and post-procedural DW-MRI. Methods We prospectively enrolled 113 consecutive patients who underwent transfemoral TAVI and post-procedural DW-MRI. We used balloon-expandable valves as first-line therapy and selected self-expandable valves only for patients with narrow sinotubular junctions or annuli. We set the primary endpoint as the number of high intensity areas (HIA) detected by DW-MRI regardless of the size of the area. To evaluate the risks of the primary endpoint, we employed a multivariable linear regression model, setting the primary endpoint as an objective variable and patient and clinical backgrounds as explanatory variables. In addition, the relationship between valve type and the number of HIAs on DW-MRI was also confirmed by the propensity score matching analysis to evaluate the robustness of the result, using a multivariable linear regression model with the protocol described in the previous manuscript. Shortly, the propensity score was calculated with a logistic regression model by setting the treatment as the response variable and baseline characteristics and procedural information that were significantly different between 2 groups (balloon expandable and self-expandable) as explanatory variables, which included age, estimated glomerular filtration rate, oversizing rate, and BAV before THV deployment. Results Median patient age was 84 years, and 36.3% were men. Ninety-three patients underwent balloon-expandable TAVI and 20 underwent self-expandable TAVI. Symptomatic stroke occurred in 6 (5.3%) whereas asymptomatic stroke occurred in 59 (52.2%) patients. The incidence of symptomatic and total stroke was higher in patients who underwent self-expandable TAVI than those who underwent balloon-expandable TAVI (30.0% vs 0.0%, p Conclusions Self-expandable valves were associated with increased numbers of HIA on DW-MRI after TAVI in patients with severe aortic stenosis.

Background Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are well-known for preventing cardiovascular disease. Among n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) play key roles in preventing cardiovascular diseases. However, the effects of n-3 PUFAs have been examined under conditions of simultaneous administration of EPA and DHA in the majority of clinical investigations and the effect of purified EPA is still controversial. EPA has been reported to improve endothelial dysfunction. Although several mechanisms underlying the effects of EPA on endothelial function have been demonstrated such as the modulation of lipid metabolism including increases in high-density lipoprotein (HDL) and/or decreases in triglyceride (TG) levels, decreases in cytokine production, and inhibition of inflammatory processes, the main mechanisms ameliorating endothelial function have not been fully determined. Purpose We sought to clarify the main factors associated with EPA administration that led to improved endothelial function. Methods Fifty-one consecutive patients with hypertriglyceridemia (mean ± SD age, 60±13 years) with no evidence of coronary artery disease (CAD) were prospectively enrolled and administered purified EPA (1800 mg/day). Forty-eight patients who were not administered EPA were enrolled as age- and sex-matched controls. Clinical variables such as body mass index, HbA1c, fasting glucose level, HDL, low-density lipoprotein, TG, systolic blood pressure, diastolic blood pressure, heart rate, interleukin-6, baseline diameter of the brachial artery, intima-media thickness of the brachial artery, and flow-mediated dilation (FMD) were examined before and after 6 months of treatment. Univariate and multivariate regression analyses were performed to examine the associations between FMD changes and clinical variables. Results FMD was significantly improved from 4.16% ± 1.88% to 6.30% ± 2.24% (p Conclusions EPA treatment improves endothelial dysfunction in patients with hypertriglyceridemia without evidence of CAD. The change in FMD was associated with the change in EPA/AA ratio alone. These finding suggest that a direct effect of EPA on the endothelium may be the predominant factor ameliorating endothelial function. Acknowledgement/Funding This study was supported, in part, by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (15K08649).

Left atrial enlargement is an independent risk factor for ischemic stroke in patients with atrial fibrillation. Little is known regarding the association between nighttime blood pressure variability and left atrial enlargement in patients with atrial fibrillation and preserved ejection fraction. The study population consisted of 140 consecutive patients with atrial fibrillation (mean age 64 ± 10 years) with preserved ejection fraction (≥50%). Nighttime blood pressure was measured at hourly intervals, using a home blood pressure monitoring device. Nighttime blood pressure variability was expressed as the standard deviation of all readings. Left atrial volume index was measured using the modified Simpson’s biplane method with transthoracic echocardiography. Multiple regression analysis indicated that nighttime mean systolic/diastolic blood pressure and its variability remained independently associated with left atrial enlargement after adjustment for age, sex, anti-hypertensive medication class, and left ventricular mass index (P

A drawback of visual assessment for late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is the subjectivity and reproducibility of the results. The aim of this study was to investigate the relationship between left ventricular (LV) reverse remodeling in response to optimal pharmacotherapies and the definite or discrepant mid-wall LGE with visual assessment in patients with dilated cardiomyopathy (DCM). A total of 65 patients who had been hospitalized with newly diagnosed DCM and had undergone CMR, were enrolled. When the visual assessment of the presence or absence of mid-wall LGE was confirmed by the two observers, patients were classified into either the positive- (n = 20) or negative-LGE (n = 29) groups. If there was discordance between the diagnoses of the two observers, patients were classified into the discrepant-LGE (n = 16) group. LV reverse remodeling was defined as an increase in LV ejection fraction by at least 10% concomitant with a decrease in the LV end-diastolic dimension by at least 10%. Among the three groups, the frequency of early LV reverse remodeling within a 1-year follow-up was significantly different (p = 0.0068). The frequency of LV reverse remodeling within a 1-year follow-up was 59, 31, and 15%, and over 2 years was 83, 62, and 40%, in patients with negative-, discrepant-LGE, and positive-LGE, respectively. The survival rate for composite end-points of cardiovascular mortality, sustained ventricular tachycardia, appropriate cardioverter-defibrillator discharge, or rehospitalization for decompensated heart failure was lower in positive-LGEs than in negative-LGEs (p =0.0011), whereas, there were no significant differences between both negative- and discrepant-LGEs, and discrepant- and positive-LGEs. This study showed that the discordance for LGE visual assessment occupied an intermediate position between positive and negative for LGE in LV reverse remodeling in patients with DCM.

Sensitive cardiac troponin I (cTnI) predicts all-cause and cardiovascular mortality in various clinical settings. However, its clinical significance in hemodialysis (HD) patients with preserved left ventricular ejection fraction (LVEF) has not been fully elucidated. This study investigated the association of cTnI with LV morphology and function, and its long-term outcome in HD patients with preserved LVEF. This prospective study consists of 96 HD patients with preserved LVEF (69 ± 8 years and 63% male) who underwent two-dimensional echocardiographic examination and biomarker tests including cTnI, brain natriuretic peptide, and high-sensitive C-reactive protein. The primary endpoint was all-cause death and secondary endpoint was cardiovascular death. Factors independently associated with cTnI were systolic blood pressure (β = - 0.239, p = 0.011), heart rate (β = 0.216, p = 0.021), LV mass index (β = 0.231, p = 0.020), and E to e' ratio (β = 0.237, p = 0.016). During a mean follow-up of 3.6 years, primary and secondary endpoints were observed in 23 (24%) and 18 (19%) patients, respectively. In the multivariate Cox proportional hazard analysis, the upper cTnI tertile has significantly increased risk of all-cause mortality [hazard ratio (HR), 2.69; 95% confidence interval (CI), 1.139-6.386; p = 0.024] and that of cardiovascular death (HR, 4.56; 95% CI 2.021-16.968; p = 0.006) independent of echocardiographic measures and other serum biomarkers. In HD patients with preserved LVEF, serum cTnI levels were significantly associated with diastolic function and risk of mortality independent of echocardiographic variables and other biomarkers.

Access challenges are sometimes encountered in patients who require transcatheter aortic valve implantation (TAVI). Transapical (TA) access is a well-established alternative, but it is more invasive than the standard transfemoral (TF) access techniques. We adopted the iliac endoconduit technique to perform TF TAVI in a patient with small-caliber, heavily calcified iliac arteries. This technique could provide an adequate access route for TAVI that is minimally invasive, even for patients with prohibitory iliac anatomy.

Abnormal P-wave characteristics were reportedly associated with left ventricular interstitial fibrosis as defined by cardiac magnetic resonance images. The objective of this study is to investigate the utility of P-wave characteristics to predict atrial fibrillation (AF) recurrence and the recovery of left ventricular systolic dysfunction (LVSD) after catheter ablation (CA) for AF. Two hundred and five AF patients (109 paroxysmal and 96 persistent) who underwent CA were enrolled. We measured maximum P-wave duration (max PWD) and P-wave terminal force in lead V1 (PTFV1) calculated as a product of P-wave terminal amplitude (PTaV1) and duration (PTdV1) in lead V1 during sinus rhythm. AF recurrence was noted in 50 patients at 12 months after CA. Patients with AF recurrence had a higher prevalence of persistent AF, a larger left atrial volume, and a longer max PWD than those without. We divided the patients into 2 groups: 156 patients with left ventricular ejection fraction (LVEF) > 45% and 49 patients with LVEF ≤ 45% (Low-EF group). In Low-EF group, tachycardia-induced cardiomyopathy (TIC) was defined as improvement in LVEF ≥ 15% or LVEF ≥ 50% at 5 months after CA. TIC and non-TIC groups consisted of 37 and 12 patients, respectively. Max PWD, PTFV1, PTdV1, and PTaV1 were significantly greater in non-TIC-group than in TIC-group. PTFV1 had the highest diagnostic accuracy to discriminate between TIC and no-TIC-groups; cut-off value for PTFV1 was determined as 56.7 mV ms (area under the ROC curve = 0.80; 75% sensitivity; and 76% specificity). Max PWD was a useful predictor of AF recurrence and the complete recovery of LVSD after CA. PTFV1 had the highest diagnostic accuracy to discriminate between TIC and no-TIC-groups.

We report a case of multiple coronary spasms leading to life-threatening ventricular arrhythmia, during left atrium (LA) ablation. Coronary artery spasm is a rare complication during radiofrequency catheter ablation of atrial fibrillation (AF). Previous reports mention that autonomic imbalance leads to coronary artery spasm and ST-segment elevation in the inferior leads, during trans-septal LA catheterization and AF ablation procedures. However, there are few reports detailing the association between ablation sites and changes in the electrocardiogram. We encountered transient ST-segment elevation and refractory ventricular arrhythmia, associated with coronary artery spasm, during radiofrequency ablation of ganglionated plexuses (superior surface of left and right atrium). .

Background Recent studies have shown that hematopoietic stem cells can undergo clonal expansion secondary to somatic mutations in leukemia-related genes, thus leading to an age-dependent accumulation of mutant leukocytes in the blood. This somatic mutation-related clonal hematopoiesis is common in healthy older individuals, but it has been associated with an increased incidence of future cardiovascular disease. The epigenetic regulator TET2 is frequently mutated in blood cells of individuals exhibiting clonal hematopoiesis. Objectives This study investigated whether Tet2 mutations within hematopoietic cells can contribute to heart failure in 2 models of cardiac injury. Methods Heart failure was induced in mice by pressure overload, achieved by transverse aortic constriction or chronic ischemia induced by the permanent ligation of the left anterior descending artery. Competitive bone marrow transplantation strategies with Tet2-deficient cells were used to mimic TET2 mutation-driven clonal hematopoiesis. Alternatively, Tet2 was specifically ablated in myeloid cells using Cre recombinase expressed from the LysM promoter. Results In both experimental heart failure models, hematopoietic or myeloid Tet2 deficiency worsened cardiac remodeling and function, in parallel with increased interleukin-1beta (IL-1β) expression. Treatment with a selective NLRP3 inflammasome inhibitor protected against the development of heart failure and eliminated the differences in cardiac parameters between Tet2-deficient and wild-type mice. Conclusions Tet2 deficiency in hematopoietic cells is associated with greater cardiac dysfunction in murine models of heart failure as a result of elevated IL-1β signaling. These data suggest that individuals with TET2-mediated clonal hematopoiesis may be at greater risk of developing heart failure and respond better to IL-1β–NLRP3 inflammasome inhibition.

Background We investigated the prevalence and prognostic significance of functional mitral regurgitation (MR) and tricuspid regurgitation (TR) in patients with atrial fibrillation (AF) and preserved left ventricular ejection fraction (LVEF).Methods and Results:We retrospectively studied the cases of 11,021 consecutive patients who had undergone transthoracic echocardiography. AF appeared in 1,194 patients, and we selected 298 with AF and LVEF ≥50% but without other underlying heart diseases. Moderate or greater (significant) degree of functional MR and of TR was seen in 24 (8.1%) and in 44 (15%) patients, respectively (P=0.0045). In contrast, significant MR and TR were more frequently seen in patients with AF duration >10 years (28% vs. 25%, respectively). During the follow-up period of 24±17 months, 35 patients (12%) met the composite endpoint defined as cardiac death, admission due to heart failure, or mitral and/or tricuspid valve surgery. On Cox proportional hazard ratio analysis, both MR and TR grading predicted the endpoint, independently of other echocardiographic parameters. On Kaplan-Meyer analysis, presence of both significant functional MR and TR was associated with poor prognosis, with an event-free rate of only 21% at the mean follow-up period of 24 months. Conclusions Significant functional MR and TR are seen in a substantial proportion of patients with longstanding AF, despite preserved LVEF. This MR/TR combination predicts poor outcome for AF patients, who may have to be treated more intensively.

BACKGROUND Alteration in mitral valve morphology resulting from retrograde stiff wire entanglement sometimes causes hemodynamically significant acute mitral regurgitation (MR) during transfemoral transcatheter aortic valve replacement (TAVR). Little is known about the echocardiographic parameters related to hemodynamically significant acute MR. METHODS AND RESULTS This study population consisted of 64 consecutive patients who underwent transfemoral TAVR. We defined hemodynamically significant acute MR as changes in the severity of MR with persistent hypotension (systolic blood pressure

The presence of a patent foramen ovale (PFO) has been found to be associated with an increased risk of cryptogenic stroke in many case-control studies. This paper reviews the current understanding of the pathophysiology and diagnosis of PFO, and therapeutic options of patients with PFO and cryptogenic stroke.

Highlights • Differences in risk factors for SBI between paroxysmal and persistent AF was studied. • NVAF patients (119 paroxysmal, 71 persistent) underwent brain MRI, TTE, and TEE. • DM and CKD, which represents microvascular disease, predicted SBI in paroxysmal AF. • There was no obvious therapeutic target for SBI after progression to persistent NVAF. • Intervention for DM and CKD from paroxysmal NVAF may prevent SBI and future stroke., Background Although silent brain infarction is an independent risk factor for subsequent symptomatic stroke and dementia in patients with nonvalvular atrial fibrillation, little is known regarding differences in risk factors for silent brain infarction between patients with paroxysmal and persistent nonvalvular atrial fibrillation. Methods This study population consisted of 190 neurologically asymptomatic patients (mean age, 64 ± 11 years) with nonvalvular atrial fibrillation (119 paroxysmal, 71 persistent) who were scheduled for catheter ablation. All patients underwent brain magnetic resonance imaging to screen for silent brain infarction prior to ablation. Transthoracic and transesophageal echocardiography was performed to screen for left atrial abnormalities (left atrial enlargement, spontaneous echo contrast, or left atrial appendage emptying velocity) and complex plaques in the aortic arch. Results Silent brain infarction was detected in 50 patients (26%) [26 patients (22%) in paroxysmal vs. 24 patients (34%) in persistent, p = 0.09]. Multiple logistic regression analysis indicated that age and diabetes mellitus or chronic kidney disease (estimated glomerular filtration rate

Objectives The NIPPON (Nobori Dual Antiplatelet Therapy as Appropriate Duration) study was a multicenter randomized investigation of the noninferiority of short-term versus long-term dual antiplatelet therapy (DAPT) in patients with implantation of the Nobori drug-eluting stent (DES) (Terumo, Tokyo, Japan), which has a biodegradable abluminal coating. Background The optimum duration of DAPT for patients with a biodegradable polymer-coated DES is unclear. Methods The subjects were 3,773 patients with stable or acute coronary syndromes undergoing Nobori stent implantation. They were randomized 1:1 to receive DAPT for 6 or 18 months. The primary endpoint was net adverse clinical and cerebrovascular events (NACCE) (all-cause mortality, myocardial infarction, stroke, and major bleeding) from 6 to 18 months after stenting. Intention-to-treat analysis was performed in 3,307 patients who were followed for at least 6 months. Results NACCE occurred in 34 patients (2.1%) receiving short-term DAPT and 24 patients (1.5%) receiving long-term DAPT (difference 0.6%, 95% confidence interval [CI]: 1.5 to 0.3). Because the lower limit of the 95% CI was inside the specified margin of −2%, noninferiority of short-term DAPT was confirmed. Mortality was 1.0% with short-term DAPT versus 0.4% with long-term DAPT, whereas myocardial infarction was 0.2% versus 0.1%, and major bleeding was 0.7% versus 0.7%, respectively. The estimated probability of NACCE was lower in the long-term DAPT group (hazard ratio: 1.44, 95% CI: 0.86 to 2.43). Conclusions Six months of DAPT was not inferior to 18 months of DAPT following implantation of a DES with a biodegradable abluminal coating. However, this result needs to be interpreted with caution given the open-label design and wide noninferiority margin of the present study. (Nobori Dual Antiplatelet Therapy as Appropriate Duration [NIPPON]; NCT01514227)

Objectives The purpose of this study was to clarify the prognostic significance of diagnosing whether the failing heart is functioning on the descending limb of the Starling curve by using echocardiography with passive leg lifting (PLL). Background Patients with advanced heart failure can shift to the descending limb of the Starling curve, in which pre-load does not lead to an expected increase in forward left ventricular stroke volume (LVSV). Methods Thirty-five consecutive patients with left ventricular (LV) ejection fraction of Results Despite PLL, a paradoxical decrease in forward LVSV was observed in 15 (43%) patients. Changes in forward LVSV inversely correlated with those in functional mitral regurgitation (r = −0.56). The primary endpoint of cardiac death or hospitalization due to worsening heart failure occurred in 15 (43%) patients during follow-up (2.8 ± 2.2 years). There were a number of significant predictors of the primary endpoint in the univariate Cox analysis: baseline E/A ratio (p = 0.0002), paradoxical decrease in LVSV despite PLL (hazard ratio: 4.44; 95% confidence interval: 1.41 to 14.0; p = 0.011), baseline LV end-systolic volume (p = 0.023), and baseline LV ejection fraction (p = 0.034). In the bivariate Cox analysis, an addition of the paradoxical decrease in LVSV significantly enhanced the predictive power of all other univariate predictors. Conclusions Heart failure patients with LV systolic dysfunction on the descending limb of the Starling curve can be recognized by the paradoxical decrease in LVSV despite PLL, and the prognostic predicting power is additive to the other traditional echocardiographic predictors. Also, our results suggest that functional mitral regurgitation is an important reason for the descending limb of the Starling curve, which is clinically recognized as the pre-load–induced decrease in forward LVSV.