Search

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....

Pulmonary arterial hypertension (PAH) is a progressive condition that frequently results in right ventricular (RV) remodeling. The objectives of this study are to investigate effects of rivaroxaban on RV remodeling in a rat model of PAH, created with Sugen5416 and chronic hypoxia, and the in vitro effects of rivaroxaban on human cardiac microvascular endothelial cells (HCMECs). To create the PAH model, male Sprague-Dawley rats were subcutaneously injected with Sugen5416 (20 mg/kg) and exposed to 2 weeks of hypoxia (10% O2), followed by 2 weeks of exposure to normoxia. The animals were then divided into 2 groups with or without administration of rivaroxaban (1.2 mg/kg/day) for a further 4 weeks. HCMECs were cultured under hypoxic conditions (37°C, 1% O2, 5% CO2) with Sugen5416 and with or without rivaroxaban. In the model rats, RV systolic pressure and Fulton index increased by hypoxia with Sugen5416 were significantly decreased when treated with rivaroxaban. In HCMECs, hypoxia with Sugen5416 increased the expression of protease-activated receptor-2 (PAR-2) and the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor-kappa B (NF-κB), while treatment with rivaroxaban significantly suppressed the expression of these proteins. Rivaroxaban attenuated RV remodeling in a rat model of PAH by reducing ERK, JNK and NF-κB activation. Rivaroxaban has the possibility of providing additive effects on RV remodeling in patients with PAH.

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.

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

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

Dipeptidyl peptidase-4 (DPP-4) inhibitors not only improve impaired glucose tolerance in diabetes, but also have pleiotropic extra-pancreatic effects such as preconditioning effect for myocardial ischemia-reperfusion injury. Here, we investigated the anti-remodeling effects of linagliptin, a DPP-4 inhibitor, by use of DPP-4-deficient rats.After the induction of myocardial infarction (MI), Fischer 344 rats with inactivating mutation of DPP-4 were orally administrated with a DPP-4 inhibitor, linagliptin (5 mg kg−1·day−1), or vehicle in drinking water for 4 weeks. Linagliptin did not affect hemodynamic status, body weight, and infarct size. In echocardiography, linagliptin tended to improve left ventricular (LV) systolic function, and significantly improved LV diastolic function, surprisingly. Interstitial fibrosis in marginal region and macrophage infiltration were significantly lower in the linagliptin group than those in the vehicle group. Fibrosis-related gene expressions, such as collagen I and transforming growth factor-β1 (TGF-β1), and inflammation-related expressions, such as macrophage chemotactic protein 1 and matrix metalloproteinase-2 (MMP-2), were significantly suppressed in marginal area of the linagliptin-treated rats compared with the vehicle rats. The TGF-β1 and MMP-2 protein levels were attenuated by linagliptin in DPP-4-deficient cardiac fibroblasts.Linagliptin can attenuate MI-induced cardiac remodeling via a DPP-4-independent pathway. Keywords: Dipeptidyl peptidase-4, Fibrosis, Left ventricular diastolic function, Macrophage, Myocardial infarction

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.

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.

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.

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.

Patients with obstructive sleep apnea (OSA) have a high prevalence of atrial fibrillation (AF). Rivaroxaban, a coagulation factor Xa inhibitor, has recently been reported to show pleiotropic effects. This study investigated the influence of rivaroxaban on cardiac remodeling caused by intermittent hypoxia (IH). Male C57BL/6J mice were exposed to IH (repeated cycles of 5% oxygen for 1.5 min followed by 21% oxygen for 5 min) for 28 days with/without rivaroxaban (12 mg/kg/day) or FSLLRY, a protease-activated receptor (PAR)-2 antagonist (10 μg/kg/day). IH caused endothelial cell degeneration in the small arteries of the right atrial myocardium and increased the level of %fibrosis and 4-hydroxy-2-nonenal protein adducts in the left ventricular myocardium. IH also increased the expression of PAR-2 as well as the phosphorylation of extracellular signal-regulated kinase (ERK)-1/2 and nuclear factor-kappa B (NF-κB) were increased in human cardiac microvascular endothelial cells. However, rivaroxaban and FSLLRY significantly suppressed these changes. These findings demonstrate that rivaroxaban attenuates both atrial and ventricular remodeling induced by IH through the prevention of oxidative stress and fibrosis by suppressing the activation of ERK and NF-κB pathways via PAR-2. Treatment with rivaroxaban could potentially become a novel therapeutic strategy for cardiac remodeling in patients with OSA and AF.

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.

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.

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

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)

There are few reports about the incidence and predictors of silent cerebral thromboembolic lesions (SCLs) after atrial fibrillation (AF) ablation in patients treated with direct oral anticoagulants (DOACs). The purpose of this study is to evaluate the incidence and predictors of SCLs after AF ablation with cerebral magnetic resonance imaging (C-MRI) in patients treated with DOACs. We enrolled 117 consecutive patients who underwent first AF ablation and received DOACs, including apixaban, dabigatran, edoxaban, and rivaroxaban. DOACs were discontinued after administration 24 h before the procedure, and restarted 6 h after the procedure. During the procedure, activated clotting time (ACT) was measured every 15 min, and intravenous heparin infusion was performed to maintain ACT at 300–350 s. All patients underwent C-MRI the day after the procedure. SCLs were detected in 28 patients (24%) after AF ablation. Age, female sex, the presence of persistent AF, left atrial volume, procedure time, radiofrequency energy, electrical cardioversion, and mean ACT showed no correlations with the incidence of SCLs. Multivariate analysis revealed independent predictors of SCLs were CHA2DS2VASc scores ≥3, left atrial appendage (LAA) emptying velocity ≤39 cm/s, and minimum ACT ≤260 s. Patients with both CHA2DS2VASc scores ≥3 and LAA flow velocity ≤39 cm/s had the highest incidence of SCLs 15 of 26 patients (58%). In patients treated with DOACs, CHA2DS2VASc score ≥3, minimum ACT ≤260 s, and LAA emptying velocity ≤39 cm/s were independent risk factors for the SCLs after AF ablation.

Non-invasive risk stratification for ventricular fibrillation (VF) in Brugada syndrome (BrS) has not been fully evaluated. The aim of this study was to assess the utility of signal-averaged Holter electrocardiogram (Holter SAECG) and 12-lead Holter electrocardiogram (Holter ECG) after a pilsicainide provocation test for non-invasive risk stratification in BrS. We enrolled 30 consecutive patients with BrS [divided into 2 groups: the VF group, those with a previous history of VF (n = 10); and the non-VF group, those without a history of VF (n = 20)] and 10 control subjects without type 1 ECG. We evaluated late potentials [LP: filtered QRS (f-QRS), RMS40, and LAS40] on the Holter SAECG for 4 h after the pilsicainide provocation and in the same patients on another day without performing the pilsicainide provocation. Furthermore, we measured QRS duration and QTc interval in leads V2 and V5, and J amplitude in lead V2 on the Holter ECG after the pilsicainide provocation. On the Holter SAECG, the f-QRS at 1 h and LAS40 at 3 h after the pilsicainide provocation were significantly larger in the VF group than in the non-VF group (f-QRS at 1 h: 113.9 ± 8.9 vs. 104.9 ± 8 ms; p = 0.01, LAS40 at 3 h: 45.4 ± 5.9 vs. 35.5 ± 7.4 ms; p

Background We have previously reported the usefulness of our newly developed visual aortic stenosis (AS) score in screening for AS using pocket-sized echocardiography. The objective of this study was to investigate whether the visual AS score and/or conventional aortic valve calcification score derived from pocket-sized echocardiography can be used to predict AS-related events. Methods One hundred and nine patients with systolic ejection murmur (SEM) or known AS (64 males, age 75 ± 9 years) were enrolled and a visual AS score and an aortic valve calcification score were assessed using pocket-sized echocardiography. The primary endpoint was defined as AS-related events, including cardiac death and aortic valve replacement, during the follow-up period. Results In a multivariate Cox proportional hazards analysis, AS-related events were independently predicted by an aortic valve calcification score ≥3 (HR, 3.5; 95% CI, 1.1–11; p = 0.033) and a visual AS score ≥3 (HR, 15; 95% CI, 1.8–125; p = 0.013). During 18 ± 9 months of follow-up, the event-free survival rate was 98% in patients with both a visual AS score

It has been reported that rhythm control for persistent atrial fibrillation (per-AF) patients by catheter ablation improves their exercise tolerance, subjective symptoms, and quality of life (QoL). However, clinical factors that can predict future improvement of exercise capacity after successful catheter ablation in per-AF patients are unclear.This study consisted of 62 patients (mean age 65.6 ± 8.7 years, 77% males) with per-AF who underwent catheter ablation from June 2017 to May 2018. All patients were subjected to extended pulmonary vein isolation. Exercise tolerance was evaluated using a symptom-limited cardiopulmonary exercise test before and 3 months after catheter ablation. Primary endpoints were QoL measurements using an original questionnaire and functional assessments performed at 3 months.The questionnaire revealed significant improvement in QoL after catheter ablation (minimal metabolic equivalents occurring symptoms: from 5.48 ± 1.14 to 5.64 ± 1.06; p = 0.01). Endurance exercise characteristics improved significantly after catheter ablation, demonstrated by a shift in anaerobic threshold (from 13.3 ± 3.0 to 15.2 ± 3.3 ml/kg/min; p 0.001), peak oxygen uptake (from 19.1 ± 4.6 to 22.5 ± 5.0 ml/kg/min; p 0.001), and minute ventilation vs carbon dioxide production slope (from 28.3 ± 6.1 to 25.7 ± 3.8; p 0.001). Multivariate Cox regression analysis revealed that a decreased left ventricular ejection fraction, high left atrial appendage velocity, and high CHADSCatheter ablation for per-AF patients improves QoL and exercise tolerance. The effect was especially remarkable in patients with reduced ventricular function, those who had a preserved atrial function, or those at high risk of thromboembolism.

Soluble urokinase-type plasminogen activator receptor (suPAR) is a membrane-binding protein that is released into the blood stream by immune activation. Recent reports suggest that circulating suPAR levels are associated with adverse cardiovascular outcomes. Exercise tolerance is an independent predictor of prognosis in patients with heart failure (HF); however, the relationship between serum suPAR level and exercise tolerance is unclear. We prospectively enrolled 94 patients who were hospitalized for worsening of HF. All patients underwent a symptom-limited cardiopulmonary exercise test to evaluate exercise tolerance. The median value of serum suPAR was 4848 pg/ml. During follow up, 44 patients (47%) were admitted for all-cause mortality and re-hospitalization for HF. Median serum suPAR was significantly higher in the patients with cardiac events than in the patients with non-event group. Patients were divided into two groups according to circulating suPAR levels. Kaplan–Meier analysis demonstrated that adverse cardiac events were significantly higher in the high suPAR group (log-rank p = 0.023). Multivariate analysis revealed that suPAR was independently correlated with the parameters of exercise tolerance such as anaerobic threshold (p = 0.007) and peak oxygen uptake (p = 0.005). suPAR levels predicted adverse cardiac events and independently correlated with the parameters of exercise tolerance. suPAR could be a useful surrogate biomarker of exercise tolerance in patients with HF.

OBJECTIVES In this study, we sought to investigate the association between revolution speed of rotational atherectomy (RA) and debulking area assessed by frequency domain-optical coherence tomography (FD-OCT). BACKGROUND The number of patients with severe calcified coronary artery disease requiring treatment with calcium ablation, such as RA, is increasing. However, there is little evidence available regarding the association between debulking area and revolution speed during RA. METHODS We retrospectively investigated 30 consecutive severely calcified coronary lesions in 29 patients who underwent RA under FD-OCT guidance. The association between preset revolution speed of RA and burr size-corrected debulking area of the calcified lesion was evaluated using a multivariable regression model with nonlinear restricted-cubic-spline, which can help assess nonlinear associations between variables. RESULTS The median age of study participants was 73 years (quartile 65-78); 82.8% were male. The median burr size was 1.5 mm (1.5-1.75); median total duration of ablation was 120 s (100-180). FD-OCT revealed that the post-procedural minimum lumen area increased significantly from 1.64 mm2 (1.40-2.09) to 2.45 mm2 (2.11-2.98) (p

BACKGROUND AND OBJECTIVES This study aimed to evaluate the utility of high-sensitive troponin T (hs-TnT) for predicting AF recurrence and major adverse cardiovascular events (MACE) after AF ablation. METHODS AND RESULTS A total of 227 consecutive patients with AF (mean age, 66 ± 10 years; persistent AF, n = 98) who underwent an initial ablation were enrolled. We measured hs-TnT before AF ablation and divided the patients into three groups according to the hs-TnT level: low, lesser than or equal to 0.005 µg/L (n = 54); medium, 0.006-0.013 µg/L (n = 127); and high, greater than or equal to0.014 µg/L (n = 46). We evaluated the composite endpoint of AF recurrence or MACE (including death, stroke, acute coronary syndrome, and heart failure hospitalization) after the ablation. The median hs-TnT level was 0.008 µg/L. The values of chronic kidney disease prevalence, CHA2 DS2 -VASc score, B-type natriuretic peptide level, and left atrial diameter were the highest in the high hs-TnT group among the three groups. During a mean follow-up of 15 ± 8 months, AF recurrence and MACE occurred in 56 (25%) and 9 (4%) patients, respectively. The high hs-TnT group had the highest incidence of AF recurrence and MACE among the three groups (high: 39% and 15%, medium: 22% and 2%, and low: 19% and 0%, respectively; log-rank P

Background Although ankle‐brachial index (ABI) and brachial‐ankle pulse wave velocity (baPWV) are significant predictors of major adverse cardiovascular event (MACE), their prognostic value in association with biomarkers has not been fully evaluated in patients with end‐stage kidney disease (ESKD). Hypothesis We hypothesized that ABI/baPWV would provide better prognostic value independent of biomarkers in ESKD patients. Methods This study included 104 ESKD patients treated with maintenance hemodialysis who underwent ABI and baPWV examinations and laboratory tests, including brain‐natriuretic peptide, high‐sensitive cardiac troponin T (hs‐cTnT), and high‐sensitive C‐reactive protein (hs‐CRP). MACE was defined as a composite event of all‐cause death, acute coronary syndrome, and stroke. Results During a mean follow‐up of 3.6 ± 1.7 years, a total of 51 MACE were observed. The independent factors associated with MACE were age >75 years (adjusted hazard ratio [HR], 2.15; P

Background Cardio-ankle vascular index (CAVI) is a marker that reflects the overall stiffness of the aorta, femoral artery, and tibial artery. Several previous reports have shown the usefulness of CAVI for coronary artery disease (CAD) presence and severity. According to coronary angiography (CAG) and intracoronary imaging such as optical coherence tomography (OCT), coronary plaque burden and morphology as predictors of all-cause and cardiovascular mortality were previously evaluated. The aim of our study was to assess the correlation between CAVI value and Gensini's score for the coronary plaque burden as well as CAVI value and plaque morphology by using OCT. Methods A total of 548 consecutive patients who underwent CAG were enrolled in this study. CAVI value was evaluated in all patients, and OCT was performed in 89 of the 548 patients. CAVI ratio is calculated as CAVI/CAVIex (expected normal value of CAVI, which is calculated using patient age and sex). Results On multivariable analysis, sex, age, hypertension, diabetes mellitus, and CAVI were significantly correlated with logarithmized Gensini's score. CAVI values were significantly higher in the groups with CAD, which were 1 vessel disease (VD), 2VD, and 3VD, than in the OVD group (p0.001). However, there was no statistical significance between CAVI ratio and OCT findings in terms of plaque morphology. Conclusions CAVI might be useful as a routine test for the detection of CAD and the evaluation of atherosclerotic plaque burden but not coronary plaque vulnerability.

Little evidence is available regarding the risk of peri-procedural stroke detected by diffusion-weighted magnetic resonance imaging (DW-MRI) after transcatheter aortic valve replacement (TAVR). Our purpose was to evaluate stroke risk after TAVR using DW-MRI by enrolling consecutive patients who underwent transfemoral TAVR and post-procedural DW-MRI.We prospectively enrolled 113 consecutive patients who underwent transfemoral TAVR 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.Median patient age was 84 years, and 36.3% were men. Ninety-three patients underwent balloon-expandable TAVR and 20 underwent self-expandable TAVR. 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 TAVR than those who underwent balloon-expandable TAVR (30.0% vs. 0.0%, p0.001 and 90.0% vs. 50.5%, p=0.001, respectively). A multivariable linear regression model demonstrated an increased primary endpoint when self-expandable TAVR was performed (p0.001). The other covariates had no significant relationship to the primary endpoint. Akaike information criterion-based stepwise statistical model selection revealed that valve type was the only explanatory variable for the best predictive model.Self-expandable valves were associated with increased numbers of HIA on DW-MRI after TAVR in patients with severe aortic stenosis.

The prognostic value of the seasonal variations of T-wave alternans (TWA) and heart rate variability (HRV), and the seasonal distribution of ventricular fibrillation (VF) in Brugada syndrome (Br-S) is unknown. We assessed the utility of seasonal variations in TWA and HRV for risk stratification in Br-S using a 24-h multichannel Holter electrocardiogram (24-M-ECG). We enrolled 81 patients with Br-S (grouped according to their history of VF, n = 12; syncope, n = 8; no symptoms, n = 61) who underwent 24-M-ECG in all four seasons. Precordial electrodes were attached to the third (3L-V2) and fourth (4L-V2, 4L-V5) intercostal spaces. We determined the maximum TWA (max-TWA) values and calculated HRV during night and morning time periods for all seasons. During a follow-up period of 5.8 ± 2.8 years, 11 patients experienced new VF episodes and there was a peak in new VF episodes in the summer. The VF group had the greatest 3L-V2 max-TWA value during morning time in the summer among the three groups and showed higher 3L-V2 max-TWA value than in the other seasons. The cutoff value for the 3L-V2 max-TWA during morning time in the summer was determined to be 42 µV using ROC analysis (82 % sensitivity, 74 % specificity; p = 0.0006). Multivariate analysis revealed that a 3L-V2 max-TWA value ≥42 µV during morning time in the summer and previous VF episodes were predictors of future VF episodes. The 3L-V2 max-TWA value during morning time in the summer may be a useful predictor of future VF episodes in Br-S.

In patients with congestive heart failure and renal dysfunction, high dose of diuretics are necessary to improve congestion, which may progress to renal dysfunction. We examined the efficacy of tolvaptan with reduction of loop diuretics to improve renal function in patients with congestive heart failure and renal dysfunction. We conducted a multicenter, prospective, randomized study in 44 patients with congestive heart failure and renal dysfunction (serum creatinine concentration ≥1.1 mg/dl) treated with conventional diuretics. Patients were randomly divided into two groups: tolvaptan (15 mg) with a fixed dose of diuretics or with reducing to a half-dose of diuretics for 7-14 consecutive days. We examined the change of urine volume, body weight, serum creatinine and electrolyte concentrations in each group. Both groups demonstrated significant urine volume increase (724 ± 176 ml/day in the fixed-dose group and 736 ± 114 ml/day in the half-dose group) and body weight reduction (1.6 ± 1.5 kg and 1.6 ± 1.9 kg, respectively) from baseline, with no differences between the two groups. Serum creatinine concentration was significantly increased in the fixed-dose group (from 1.60 ± 0.47 to 1.74 ± 0.66 mg/dl, p = 0.03) and decreased in the half-dose group (from 1.98 ± 0.91 to 1.91 ± 0.97 mg/dl, p = 0.10). So the mean changes in serum creatinine concentration from baseline significantly differed between the two groups (0.14 ± 0.08 mg/dl in the fixed-dose group and -0.07 ± 0.19 mg/dl in the half-dose group, p = 0.006). The administration of tolvaptan with reduction of loop diuretics was clinically effective to ameliorate congestion with improving renal function in patients with congestive heart failure and renal dysfunction.

Because paravalvular leak after mitral valve replacement in highly morbid patients is a troublesome issue, there has been a growing interest in less invasive procedures. We conducted transcatheter paravalvular leak closure of a mitral valve prosthesis through left ventricular apical access. The patient had undergone redo mitral valve replacement through a transatrial septal approach 2 months prior to the procedure; thus, penetration of the atrial septum was considered to be difficult through the ordinary antegrade trans-septal approach. Transapical access for the mitral paravalvular leak was conducted using two AMPLATZER Vascular Plugs (St. Jude Medical, St. Paul, MN), with a route directed straight to the defect. This approach is an alternative technique for transcatheter paravalvular leak closure. This is the first case report of transapical access for transcatheter paravalvular leak closure in Japan.

We describe four cases of the patients with ST-elevation myocardial infarction (STEMI) that were treated with interleukin-11 (IL-11), a cardioprotective cytokine. Recombinant human IL-11 (rhIL-11), was intravenously administered to two cases at low dose (6 µg/kg) and to two at high dose (25 µg/kg). The cytokine administration started just after the coronary occlusion was confirmed by coronary angiography (CAG), taking 3 h. Following CAG, percutaneous coronary intervention (PCI) was performed as a standard therapy. No serious adverse drug reactions were observed. All the cases left the hospital without the symptom of heart failure. We discuss the possibility of the clinical use of rhIL-11 as an adjunct therapy to PCI for the STEMI patients.

Brain-derived neurotropic factor (BDNF) is a myokine that plays a key role in regulating survival, growth, and maintenance of neurons. We investigated whether the serum BDNF level at discharge could predict the prognosis in patients with heart failure (HF). Furthermore, we aimed to examine the relationship between this myokine and exercise tolerance. We prospectively enrolled 94 patients who were hospitalized for worsening HF and had cardiac rehabilitation. At discharge, the serum BDNF level of all patients was measured using a commercial ELISA kit and they underwent a cardiopulmonary exercise test to measure peak oxygen uptake (peak VO2). Correlation was not observed between BDNF and peak VO2. Kaplan–Meier analysis demonstrated that cardiac death or rehospitalization owing to worsening HF was significantly higher in the low BDNF group (p = 0.023). The combination of peak VO2 and BDNF levels led to the identification of subgroups with significantly different probabilities of events (p = 0.005). In particular, in the low BDNF and low peak VO2 group, the frequency of rehospitalization within half a year after discharge was much higher than that in other groups. Multivariate analysis found BDNF as an independent factor of adverse events (hazard ratio 0.956; 95% confidence interval 0.911–0.999; p = 0.046). The serum BDNF level at discharge may be a useful biomarker of the prognosis in patients with HF. Furthermore, combining BDNF and peak VO2 may be useful for predicting early cardiac events.

Although it is well known that the prevalence of aortic arch plaques, one of the risk factors for ischemic stroke, is high in patients with severe aortic stenosis, the underlying mechanisms are not well understood. Increased day-by-day blood pressure (BP) variability is also known to be associated with stroke; however, little is known on the association between day-by-bay BP variability and aortic arch atherosclerosis in patients with aortic stenosis. Our objective was to clarify the association between day-by-day BP variables (average values and variability) and aortic arch atherosclerosis in patients with severe aortic stenosis.The study population consisted of 104 consecutive patients (mean age 75 ± 8 years) with severe aortic stenosis who were scheduled for aortic valve replacement. BP was measured in the morning in at least 4 consecutive days (mean 6.8 days) prior to the day of surgery. Large (≥4 mm), ulcerated, or mobile plaques were defined as complex plaques using transesophageal echocardiography.Cigarette smoking and all systolic BP variables were associated with the presence of complex plaques (p 0.05), whereas diastolic BP variables were not. Multiple regression analysis indicated that day-by-day mean systolic BP and day-by-day systolic BP variability remained independently associated with the presence of complex plaques (p 0.05) after adjustment for age, male sex, cigarette smoking, hypertension, hypercholesterolemia, and diabetes mellitus.These findings suggest that higher day-by-day mean systolic BP and day-by-day systolic BP variability are associated with complex plaques in the aortic arch and consequently stroke risk in patients with aortic stenosis.

Silent brain infarction (SBI) is often found in patients with atrial fibrillation (AF) and may be related to cognitive decline. We investigated the predictors of SBI on brain magnetic resonance imaging (MRI) using transesophageal echocardiography (TEE) in patients with nonvalvular AF.The study population consisted of 103 neurologically asymptomatic patients with nonvalvular AF who underwent TEE before transcatheter AF ablation (76 men; mean age 63 ± 10 years). Left atrial (LA) abnormalities such as LA thrombus, spontaneous echo contrast, or abnormal LA appendage emptying velocity (20 cm/s) and complex plaques in the aortic arch defined as large plaques ≥4 mm thickness, ulcerated plaques, or mobile plaques were evaluated by TEE. All patients were screened for SBI by brain MRI.Of 103 patients, 31 (30%) showed SBI on brain MRI. Most lesions were multiple (61%) and small (15 mm) in diameter (84%). Patients with SBI had a higher prevalence of LA abnormalities (45% vs 14%; P.001) and complex arch plaques (45% vs 7%; P.001) compared with those without SBI. In a multivariate logistic regression analysis including age and CHADS2 score ≥2, LA abnormalities (odds ratio 4.13; 95% CI 1.34-12.72; P = .014) and complex arch plaques (odds ratio 4.82; 95% CI 1.23-18.92; P = .024) were independent predictors of SBI.Left atrial abnormalities and complex arch plaques detected by TEE were closely associated with the presence of SBI on brain MRI, suggesting that microembolization of small thrombi derived from the fibrillating LA or advanced aortic atherosclerotic lesions may be important causes of SBI in patients with nonvalvular AF.

Percutaneous treatment with carbon dioxide (CO2) mist, CO2 gas dissolved in water, contributes to improved cardiac function after myocardial infarction (MI). In this study, we investigated the effects of repeated pretreatment with CO2 mist on cardiac dysfunction after MI. The CO2 mist was generated by a dry mist production unit. The whole body of rats below the axilla was wrapped in a polyethylene bag, which was sealed and filled with the CO2 mist in the draft cabinet for 30 min daily for 7 days. MI was induced by ligation of the coronary artery in untreated (UT), CO2 gas-pretreated (CG), and CO2 mist-pretreated (CM) rats. The infarct size and the increase in oxidative stress due to MI were significantly smaller in the CM rats than in the UT rats. Furthermore, the expression of inflammation-related genes, such as monocyte chemoattractant protein-1, and fibrosis-related genes, such as transforming growth factor-β1, was significantly suppressed in the CM rats. The CM rats had a better left ventricular ejection fraction than the UT rats 7 days after MI. These parameters in the CG rats were the same as in the UT group. Thus, CO2 mist preparative treatment may be potentially useful for the reduction of MI.

Many investigators have reported that the total amount of coronary calcium correlates with the overall magnitude of atherosclerotic plaque burden in the entire coronary tree and is a powerful predictor of future cardiovascular events. However, the development and spatial distribution of coronary calcifications remain unclear. We investigated the spatial distribution of calcifications throughout the coronary tree during coronary artery evaluation using coronary computed tomography angiography (CTA). A further aim was to assess the progression of existing calcifications and the development of new deposits in a follow-up study. The study population consisted of 287 patients for the cross-sectional study using CTA to evaluate the spatial distribution of calcifications by parent coronary arteries. Next, we analyzed a CTA dataset of 57 patients who had undergone two CTA examinations. In this group, the two CTA images were used for assessing the progression of existing calcifications and the development of new deposits. The coronary calcifications tended to be clustered within the proximal and middle portions. Moreover, in the proximal left anterior descending coronary artery (LAD), small calcifications were located more toward the inner pericardial side. Finally, new calcium deposits developed within the proximal and middle portions of the LAD and left circumflex coronary artery, but those in the right coronary artery were likely to appear evenly from the proximal to the distal portion. This study shows the characteristic patterns of the longitudinal and circumferential distribution of calcifications by parent coronary arteries.

Background Remote ischemic conditioning (RIC) by repeated treatment of transient limb ischemia is a clinically applicable method for protecting the heart against injury at the time of reperfusion. In this study, we investigated the effects of repeated RIC on cardiac dysfunction after myocardial infarction (MI). Methods and results At 4weeks after MI, rats were separated into the untreated (UT) group or the RIC-treated group. RIC treatment was performed by 5cycles of 5min of bilateral hindlimb ischemia and 5min of reperfusion once a day for 4weeks. Despite comparable MI size, left ventricular (LV) ejection fraction (LVEF) was significantly improved in the RIC group compared with the UT group. Furthermore, the LVEF in the RIC group was improved, although not significantly, after treatment. RIC treatment also prevented the deterioration of LV diastolic function. MI-induced LV interstitial fibrosis in the boundary region and oxidant stress were significantly attenuated by RIC treatment. MicroRNA-29a (miR-29a), a key regulator of tissue fibrosis, was highly expressed in the exosomes and the marginal area of the RIC group. Even in the differentiated C2C12-derived exosomes, miR-29a expression was significantly increased under hypoxic condition. As well as miR-29a, insulin-like growth factor 1 receptor (IGF-1R) was highly expressed both in the exosomes and remote non-infarcted myocardium of the RIC group. IGF-1R expression was also increased in the C2C12-derived exosomes under hypoxic conditions. Conclusions Repeated RIC reduces adverse LV remodeling and oxidative stress by MI. Exosome-mediated intercellular communication may contribute to the beneficial effect of RIC treatment.

Aim: Highly concentrated carbon dioxide (CO2) is thought to be useful for ischemic diseases. We investigated whether treatment with a few micrometers of CO2 molecules atomized via two fluidnozzles (CO2 mist) exerts an angiogenic effect in a mouse ischemic hindlimb model. Methods: Mice with unilateral hindlimb ischemia were divided into untreated (UT), 100% CO2 gas alone-treated (CG), mixed air (O2; 20%, N2; 80%) mist-treated (AM) and 100% CO2 mist-treated (CM) groups. The lower body of the mice was encased in a polyethylene bag filled with each gaseous agent using a gas mist generator for 10 minutes daily. Results: According to a laser Doppler analysis, the ischemic hindlimb blood flow was persistently higher after the seventh day of induction of ischemia in the CM group than in the UT group. The capillary density was also greater in the CM group on day 28 compared with that observed in the UT group. In addition, the parameters in the AM and CG groups were similar to those obtained in the UT group. The observed effects were abolished by the administration of an inhibitor of nitric oxide synthase (NOS). The vascular endothelial growth factor mRNA expression and protein levels and the phosphorylated endothelial NOS level were increased in the CM group compared with that observed in the UT group. A proteomic analysis using liquid chromatography-tandem mass spectrometry identified novel protein candidates regulated by CO2 mist. Conclusion: Percutaneous CO2 mist therapy may be useful for treating ischemia-induced angiogenesis.

Accelerated atherosclerosis occurs with a high frequency in patients with chronic kidney disease (CKD). We evaluated the association between CKD and thoracic aortic plaques using transesophageal echocardiography (TEE).This study population consisted of 297 patients who underwent TEE. Aortic plaques were evaluated in the proximal thoracic aorta (PTA) (from the ascending aorta to the aortic arch) and the distal thoracic aorta (DTA) (the descending aorta) using TEE. Aortic plaques were defined as complex plaques of ≥4 mm thickness and with ulceration or mobile components. CKD was defined as the estimated glomerular filtration rate (eGFR)60 mL/min/1.73 m(2). The association between CKD and aortic plaques was evaluated using multivariate analysis after adjusting for traditional atherosclerotic risk factors.Patients with CKD (n = 144) had a higher incidence of any plaques and complex plaques compared with those without CKD (n = 153) (85% vs. 47% and 42% vs. 17%, respectively, both P 0.001). Univariate analysis indicated that the presence of CKD was significantly associated with complex plaques both in the DTA and the PTA (both, P 0.001); however, multivariate analysis indicated that the presence of CKD was associated with only complex plaques in the DTA (P 0.05), but not with those in the PTA.The presence of CKD was associated with complex aortic plaques, with this association being stronger for complex plaques in the DTA than those in the PTA.

Background In this study, we sought to investigate the 2‐year prognostic impact of B‐type natriuretic peptide ( BNP ) levels at discharge, following transcatheter aortic valve replacement. Methods and Results We enrolled 1094 consecutive patients who underwent transcatheter aortic valve replacement between 2013 and 2016. Study patients were stratified into 2 groups according to survival classification and regression tree analysis (high versus low BNP groups). We evaluated the impact of high BNP on 2‐year mortality compared with that of low BNP using a multivariable Cox model, and assessed whether this stratification would improve predictive accuracy for determining 2‐year mortality by assessing time‐dependent net reclassification improvement and integrated discrimination improvement. The median age of patients was 85 years (quartile 82–88), and 29.2% of the study population were men. The median Society of Thoracic Surgeons score was 6.8 (4.7–9.5), and BNP at discharge was 186 (93–378) pg/mL. All‐cause mortality following discharge was 7.9% (95% CI, 5.8–9.9%) at 1 year and 15.4% (95% CI, 11.6–19.0%) at 2 years. The survival classification and regression tree analysis revealed that the discriminating BNP level to discern 2‐year mortality was 202 pg/mL, and that elevated BNP had a statistically significant impact on outcomes, with an adjusted hazard ratio of 2.28 (1.36–3.82, P =0.002). The time‐dependent net reclassification improvement ( P =0.047) and integrated discrimination improvement ( P =0.029) analysis revealed that the incorporation of BNP stratification with other clinical variables significantly improved predictive accuracy for 2‐year mortality. Conclusions Elevation of BNP at discharge is associated with 2‐year mortality after transcatheter aortic valve replacement.

Several trials demonstrated that frequent right ventricular apical pacing (RVAP) was associated with cardiac dysfunction and an increased rate of heart failure hospitalization. However, there are few reports about the 12-lead electrocardiogram (12-ECG) parameters at the time of device implantation to predict deterioration of LVEF in patients with frequent RVAP. We retrospectively studied 115 consecutive patients undergoing pacemaker or implantable cardioverter-defibrillator implantation with RVAP, with rate of ventricular pacing ≥ 40% and LVEF ≥ 50% at the time of implantation. We compared the 12-ECG characteristics at the time of device implantation between patients with deterioration of LVEF (≥ 10% reduction) and those without. Twenty-nine patients (25%) had deteriorated LVEF with a decrease in mean LVEF from 59 to 40% during a median follow-up period of 8.9 [4.6–13.7] years. Multivariate logistic regression analysis showed that cumulative % of ventricular pacing [odds ratio (OR) 1.04 per 1% increase, 95% confidence interval (CI) 1.01–1.09, p = 0.04], notching of baseline paced QRS in limb leads (OR 5.04, 95% CI 1.59–19.6, p = 0.005) and the QS pattern in all precordial leads (OR 3.56, 95% CI 1.21–10.8, p = 0.02) were independently associated with deterioration of LVEF. The QS pattern of baseline paced QRS in all precordial leads had 58% sensitivity, 93% specificity for the RV lead position at the tip of RV apex. In conclusion, considering OR by multivariate analysis, notching of baseline paced QRS in limb leads and the QS pattern in all precordial leads at device implantation may be simple and useful predictors to identify patients who are at risk for deterioration of cardiac function during long-term RVAP. 12-ECG monitoring at device implantation and avoidance of the RVAP site showing a QS pattern may be important to prevent deterioration of cardiac function in patients with frequent RVAP.

Aims Although right ventricular septal pacing is thought to be more effective in minimizing pacing-induced left ventricular dysfunction, the accurate way to anchor the lead to the right ventricular septum (RVS) has not been established. Our aim was to clarify the usefulness of right ventriculography (RVG) to aid accurate anchoring of the lead to the RVS. Methods and results Eighty-four patients who underwent pacemaker implantation were enrolled. We anchored the lead to the RVS by using an RVG image obtained at a 30° right anterior oblique view as a reference. We confirmed the actual lead position by performing computed tomography after the procedure and examined the characteristics of the paced QRS complex. Of the 81 patients, except 3 patients whose leads were anchored to the apex due to high pacing thresholds in the RVS, the leads were successfully anchored to the RVS in the 79 (98%) patients, and the number of leads placed in the high-, mid-, and low-RVS was 3 (4%), 58 (73%), and 18 (23%), respectively. The paced QRS duration in these 79 patients was 140 ± 13 ms. The paced QRS duration from mid-RVS was considerably narrower than that from high- or low-RVS (137 ± 12 ms vs. 146 ± 12 ms; P = 0.012). Conclusion Right ventriculography was very useful in aiding accurate anchoring of the lead to the RVS. Further, pacing from mid-RVS may be more effective in minimizing the QRS duration than pacing from other RVS sites.

BACKGROUND Balloon aortic valvuloplasty (BAV) is resurging as a bridge treatment in patients with severe aortic stenosis (AS) with a dissemination of transcatheter aortic valve implantation. However, the significantly high periprocedural mortality and complication rates still limit the indications of BAV. Further efforts are needed to improve the safety and efficacy of BAV.Methods and Results:We retrospectively investigated the safety and efficacy of simultaneous biplane mode of 3-dimensional transesophageal echocardiography (biplane-TEE) guided antegrade transseptal multiple-inflation BAV, with gradual upsizing of the balloon, by enrolling 20 consecutive AS patients who underwent BAV. The median age was 83 years, and there were 6 male patients (30.0%). The clinical frailty scale was 4, and the Society of Thoracic Surgeon score was 14.5%. The balloon was inflated at a median of 18 times, which improved the mean aortic valve pressure gradient from 43.0 to 15.2 mmHg (P

Pheochromocytoma multisystem crisis is a rare and life-threatening disease that is associated with numerous symptoms and which is also difficult to diagnose. We herein report an autopsy case of a 61-year-old man who died due to pheochromocytoma multisystem crisis. The patient complained of vomiting and breathlessness. Computed tomography showed a shadow-like region with a similar appearance to interstitial pneumonia. The patient was diagnosed with takotsubo cardiomyopathy induced by severe lung disease based on the results of echocardiography and coronary angiography. The patient was treated for interstitial pneumonia. However, his condition rapidly deteriorated and he died 6 hours after arrival. We were later informed of his extremely high catecholamine serum levels. We found pheochromocytoma with hemorrhage at autopsy. The patient's lungs showed acute passive congestion with edema and extravasation.