小林 欣夫

Although atrial ischemic damage is an atrial fibrillation (AF) risk factor, the impact of atrial branches' occlusion on AF development after acute myocardial infarction (AMI) is unclear. Therefore, this study's purpose was to identify predictors of new-onset AF with regard to atrial branches' occlusion. We retrospectively analyzed the AMI database at our single center. Consecutive patients with AMI from June 2011 to May 2017 were enrolled. Exclusion criteria were prior AF before AMI, hemodialysis, and follow-up of < 30 days. The study enrolled 204 consecutive patients (follow-up, 543 ± 469 days; age, 66 ± 12 years; male sex, 77%). All patients underwent primary percutaneous coronary intervention. Thirty-six patients (18%) had new-onset AF in the hospital after AMI. The Killip classification ≥ 3 (41% versus 7%, P < 0.001), ejection fraction ≤ 35% (19% versus 5%, P = 0.014), ischemic occlusion of atrial branches (58% versus 28%, P < 0.001), and ischemic occlusion of atrial branches originating from the right coronary artery (52% versus 18%, P < 0.001) were more frequent in patients with new-onset AF. Multivariable logistic regression analysis showed that Killip classification ≥ 3 (odds ratio, 6.97; 95% confidence interval [CI], 2.77-17.52; P < 0.001), and ischemic occlusion of the atrial branch of the right coronary artery (odds ratio, 4.35; 95% confidence interval, 1.91-9.93; P < 0.001) were independent predictors of new-onset AF. Altogether, proximal occlusion in the right coronary artery involving the atrial branch is a strong predictor of new-onset AF after AMI.

Background Left ventricular (LV) recovery in takotsubo syndrome (TTS) occurs over a wide-ranging interval, varying from hours to weeks. We sought to investigate the clinical predictors and prognostic impact of recovery time for TTS patients. Methods and Results TTS patients from the International Takotsubo Registry were included in this study. Cut-off for early LV recovery was determined to be 10 days after the acute event. Multivariable logistic regression was used to assess factors associated with the absence of early recovery. In-hospital outcomes and 1-year mortality were compared for patients with versus without early recovery. We analyzed 406 patients with comprehensive and serial imaging data regarding time to recovery. Of these, 191 (47.0%) had early LV recovery and 215 (53.0%) demonstrated late LV improvement. Patients without early recovery were more often male (12.6% versus 5.2%; P=0.011) and presented more frequently with typical TTS (76.3% versus 67.0%, P=0.040). Cardiac and inflammatory markers were higher in patients without early recovery than in those with early recovery. Patients without early recovery showed unfavorable 1-year outcome compared with patients with early recovery (P=0.003). On multiple logistic regression, male sex, LV ejection fraction <45%, and acute neurologic disorders were associated with the absence of early recovery. Conclusions TTS patients without early LV recovery have different clinical characteristics and less favorable 1-year outcome compared with patients with early recovery. The factors associated with the absence of early recovery included male sex, reduced LV ejection fraction, and acute neurologic events. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.

Although attention has been paid to the relationship between malignant diseases and cardiovascular diseases, few data have been reported. Moreover, there have also been few reports in which the preventive factors were examined in patients with or without malignant disease histories requiring percutaneous coronary intervention (PCI).This was a retrospective, single-center, observational study. A total of 1003 post-PCI patients were divided into a malignant group, with current or past malignant disease, and a nonmalignant group. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, revascularization, and admission due to heart failure within 5 years of PCI. Kaplan-Meier analysis showed a significantly higher probability of the primary endpoint in the malignant group (P = .002). Multivariable Cox hazard analyses showed that in patients without a history of malignant, body mass index (BMI) and the presence of dyslipidemia were independent and significant negative predictors of the primary endpoint (BMI: hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.53-0.99, P = .041; prevalence of dyslipidemia: HR 0.72, 95% CI 0.52-0.99, P = .048), and the presence of multi-vessel disease (MVD) and the prevalence of peripheral artery disease (PAD) were independent and significant positive predictors of the primary endpoint (prevalence of MVD: HR 1.68, 95% CI 1.18-2.40, P = .004; prevalence of PAD: HR 1.51, 95% CI 1.03-2.21, P = .034). In patients with histories of malignancy, no significant independent predictive factors were identified.Patients undergoing PCI with malignancy had significantly higher rates of adverse cardiovascular events but might not have the conventional prognostic factors.

Although it has been reported that prasugrel achieves stronger antiplatelet effect and fewer cardiovascular events compared to clopidogrel in Japanese patients, there are limited data comparing the safety between the 2 dose regimens. Data from 1031 consecutive patients with coronary artery disease undergoing PCI at 5 institutions from May 2014 to April 2016, who received aspirin plus either clopidogrel (619 patients) or prasugrel (412 patients), were retrospectively analyzed. The choice of clopidogrel or prasugrel was left to the operator's discretion. Adverse events were defined as a composite of bleeding, hepatopathy, leukopenia, thrombopenia, exanthema, and major adverse cardiovascular events (MACE). MACE was defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke. The average follow-up period was 143 days in the prasugrel group and 263 days in the clopidogrel group. Adverse events occurred in 34.5% of patients in the prasugrel group and in 28.6% in the clopidogrel group. Although the Kaplan-Meier curves showed lower survival rates from MACE, all-bleeding, major bleeding, minor bleeding, and adverse events, in the prasugrel group compared to the clopidogrel group (log rank test p = 0.009, p = 0.001, p = 0.012, p = 0.018, and p < 0.001, respectively), multivariate Cox-regression analyses determined prasugrel as a significant risk factor for all-bleeding, minor bleeding, and adverse events, but not for MACE and major bleeding events. Dual antiplatelet therapy with prasugrel was independently associated with minor bleeding events, but not with MACE and major bleeding events, compared to clopidogrel, after PCI in common clinical settings.

Familial hypercholesterolemia (FH) is reportedly associated with the development of coronary artery disease (CAD), especially acute coronary syndrome (ACS). However, the prevalence of FH in patients with stable CAD is still unclear. The aim of this study was to investigate the prevalence of Achilles tendon xanthoma (ATX) and heterozygous FH in patients with stable CAD and ACS undergoing percutaneous coronary intervention (PCI). A total of 423 patients with CAD (273 stable CAD and 150 ACS) undergoing PCI at Chiba University Hospital between June 2016 and February 2018 were enrolled in this study. Soft X-ray radiography of the Achilles tendon was performed in all patients, and a maximum thickness of 9 mm or more is regarded as ATX. Heterozygous FH was diagnosed according to the Japan Atherosclerosis Society Guidelines. In comparisons between stable CAD and ACS patients, ATX was observed in 9.2% vs. 15.3% (p = 0.055), and heterozygous FH was diagnosed in 3.7% vs. 5.3% (p = 0.416), respectively. Among ACS patients, those with ST elevation myocardial infarction (STEMI) showed the highest prevalence of ATX (19.5%) and FH (7.3%). Whereas ATX and heterozygous FH were considerably observed in patients with ACS, a certain number of ATX and heterozygous FH were also detected in stable CAD patients.

BACKGROUND: Atrial fibrillation (AF) is the most common type of arrhythmia. The definition of AF in patients with cardiac implantable electronic devices (CIEDs) is not clear, and the appropriate treatment guideline for patients with episodes of AF has not been established yet. Additionally, little is known about the incidence of AF and embolic stroke events in Japanese patients with CIEDs. The purposes of this study were to identify the incidence of embolic stroke events in Japanese patients with and without AF events detected by CIEDs and to examine the risk factors of embolic stroke events. METHODS: We retrospectively analyzed the database of our CIED clinic. Every 6 months, episodes of AF were checked by CIEDs. Using univariate (Student's t-test and Fisher's exact test) and multivariate analyses, we examined the characteristics and incidence of embolic stroke events and investigated the relationship between episodes of AF and the incidence of embolic stroke events. RESULTS: In this study, we enrolled 348 consecutive patients who had no prior history of AF and were not administering anticoagulants (follow-up period, 65±58 months; age, 70±16 years; male sex, 64%; implantable cardioverter defibrillator, 55%). The mean CHADS2 and CHA2DS2-VASc scores were 1.7±1.1 and 2.8±1.5 points, respectively. Fifty-five patients (16%) had AF events detected by CIEDs that lasted for ≥30s, and 23 patients (6.6%) had embolic stroke during the follow-up period. Multivariate analysis demonstrated that independent predictors for embolic stroke were a left atrial diameter ≥40mm [odds ratio (OR) 3.1, 95% confidence interval (CI) 1.2-7.9, p=0.016] and episodes of AF (OR 5.3, 95% CI 2.2-13, p=0.0003). CONCLUSIONS: Embolic stroke events are common in Japanese patients with CIEDs. AF events lasting ≥30s and an enlarged left atrium are the risk factors of embolic stroke in this population.

The SYNERGY coronary stent is new-generation drug-eluting stents, which has a thin-strut platinum-chromium platform with everolimus in a biodegradable polymer applied to the abluminal surface. It would be speculated that favorable arterial healing with early strut coverage could be achieved. The present study investigated the degree of strut coverage using optical coherence tomography (OCT) 2 weeks after SYNERGY implantation and clinical factors contributing to strut coverage. A total of 29 patients who underwent staged percutaneous coronary intervention (PCI) to residual lesions 2 weeks after the index PCI with SYNERGY stent implantation were enrolled. At the time of staged PCI, OCT examinations of the SYNERGY stent were performed for conventional OCT analysis on both cross-sectional and strut level. SYNERGY stent showed a high level of strut coverage and apposition, and the percentage was 82.4 ± 12.4% and 96.2 ± 5.0%, respectively. The lesion complexity was significantly related to greater strut coverage on univariate analysis; however, it was found to be insignificant in multivariate analysis. Our findings suggest early arterial healing after SYNERGY stent implantation.

The present study aimed to investigate whether layer-specific regional peak-systolic longitudinal strain (LS) measurement on transthoracic echocardiogram (TTE) with exercise stress can be useful for the detection of functionally significant coronary artery disease as confirmed by invasive fractional flow reserve (FFR) in stable patients. This is a prospective analysis of 88 coronary arteries in 30 stable patients undergoing invasive FFR measurement and ergometer exercise stress TTE. Regional LS in the mid, endocardial and epicardial layers was calculated at rest, peak stress and early and late recovery phases after the exercise stress test. The endocardial-to-epicardial LS ratio was calculated as an indicator of endocardial-layer dependency of the left ventricular myocardium. Ischemic FFR defined as FFR ≤ 0.80 was observed in 33 of 88 coronary arteries. The mid-, endocardial- and epicardial-layer LS at early recovery (- 15.4 ± 5.2 vs. -  13.0 ± 4.4%, P = 0.040;  - 15.7 ± 5.1 vs.  - 13.2 ± 4.5%, P = 0.029;  - 14.6 ± 5.1 vs.  - 12.4 ± 4.0%, P = 0.038, respectively) and the percent change in the endocardial-to-epicardial LS ratio from baseline to peak stress, early recovery, and late recovery phases (1.5 ± 11.2% vs. 6.6 ± 10.5%, P = 0.009; 2.8 ± 8.9% vs. 7.1 ± 12.6%, P = 0.002; 5.2 ± 8.8% vs. 8.5 ± 13.7%, P = 0.026; respectively) were significantly more impaired in the ischemic territories (FFR ≤ 0.80) compared with the non-ischemic territories (FFR > 0.80). According to the receiver operating characteristic curve analysis, a combination of endocardial LS and percent change in the endocardial-to-epicardial LS ratio at early recovery phase plus visual evaluation of LV wall motion had incremental diagnostic value for the detection of the ischemic territory compared with visual evaluation alone (area under the curve = 0.752 and 0.618, P = 0.006). The results of this study suggested that assessing layer-specific LS and the endocardial-to-epicardial LS ratio after exercise stress on speckle-tracking TTE may have potential for objective and quantitative evaluation in the assessment of myocardial ischemia. Further studies in a larger population are needed to confirm these findings.

Approximately 50% of patients with acute myocardial infarction including ST segment elevation myocardial infarction and non-ST segment elevation myocardial infarction have multivessel (MV) coronary artery disease. Recently, the evidence for beneficial outcomes associated with MV percutaneous coronary intervention (PCI) compared with culprit-only PCI has increased. However, optimal timing of non-culprit revascularization, appropriate lesion assessment in non-culprit vessels, and the best treatment strategy for patients with cardiogenic shock remain unclear. This review summarizes current evidence and focuses on the PCI strategies in patients with acute myocardial infarction and MV disease.

We experienced a young woman with congestive heart failure (CHF) caused by renovascular hypertension (RVH) and subsequent hypertensive heart disease. She underwent tumor resection and intraoperative radiation therapy because of neuroblastoma at age 2. She was diagnosed with RVH and hypertensive heart disease due to radiation-induced renal artery stenosis at age 12. Thereafter, she was hospitalized with CHF caused by uncontrolled RVH at age 19, and renal autotransplantation with extraction of left kidney was performed after the recovery of CHF. Her blood pressure has been well controlled without CHF readmission during four years of follow-up after the operation.

BACKGROUND: Various immune cells are involved in different phases of cardiac repair after myocardial infarction (MI). Especially, Ly6Clow M2-like macrophages (Ly6Clo macrophages) are vital for cardiac repair after MI. However, the molecular mechanisms how Ly6Clo macrophages promote wound healing after MI are still largely unknown. METHODS AND RESULTS: Transcriptome analysis of Ly6Clo macrophages and Ly6Chigh M1-like macrophages (Ly6Chi macrophages) harvested from the infarcted heart revealed that Ly6Clo macrophages highly expressed matrix metalloproteinase (MMP)-12 mRNA compared to Ly6Chi macrophages. MMP-12 expression was enhanced in the infarcted heart and preferentially observed in Ly6Clo macrophages. Importantly, the survival rate and cardiac function after MI were significantly impaired in MMP-12-deficient (mmp12-/-) mice compared with those in wild-type mice. In addition, the extent of myocardial fibrosis and the number of myofibroblasts in the infarct area were decreased in mmp12-/- mice. MMP-9 expression and neutrophils, which are the major cellular source of MMP-9, in the infarcted heart were increased in mmp12-/- mice. Moreover, mRNA expression of neutrophil-attracting chemokines including CXCL1, CXCL2, and CXCL5 was significantly higher in mmp12-/- mice. Consistently, treatment with anti-CXCR2 antibody significantly decreased neutrophil numbers and MMP-9 expression in the infarcted heart in mmp12-/- mice. Finally, the administration of recombinant MMP-12 into the infarcted heart decreased neutrophil numbers in the infarcted heart and promoted wound healing in both wild-type mice and mmp12-/- mice. CONCLUSION: MMP-12 produced by Ly6Clo macrophages improves the survival after MI possibly through the promotion of wound healing by reducing neutrophil infiltration.

BACKGROUND: Many factors are associated with hypertension development. We focused on social participation as an aspect of social capital and investigated the contextual relationship between community-level social participation and hypertension using multilevel regression analyses. METHODS: We used cross-sectional data from the 2016 Japan Gerontological Evaluation Study-a population-based study of functionally independent adults aged 65 years or older. The sample comprised 116,013 participants nested in 818 communities. Hypertension and social capital were defined by questionnaires. Social capital was assessed at both the individual and the community levels in 3 dimensions: civic participation (as an index of social participation), social cohesion, and reciprocity. RESULTS: The prevalence rate of hypertension was 43.7%, and 44.1% of the respondents were involved in civic participation. Community-level civic participation, but not social cohesion or reciprocity, was negatively associated with hypertension in the total population (prevalence ratio (95% confidence interval): 0.98 (0.96-0.99), P = 0.004) and female group (0.97 (0.95-0.99), P = 0.015), and the association neared significance in the male group (0.98 (0.96-1.005), P = 0.13) after adjustment for individual-level social capital dimensions including civic participation, individual-level covariates, and population density as a community-level covariate. The interaction between community-level civic participation and sex in relation to hypertension was significant (P = 0.012). CONCLUSIONS: We found a contextual preventive relationship between community-level civic participation and hypertension. The design of the contextual characteristics of communities by the promotion of social participation may help reduce the prevalence of hypertension in older people.

p53 is a guardian of the genome that protects against carcinogenesis. There is accumulating evidence that p53 is activated with aging. Such activation has been reported to contribute to various age-associated pathologies, but its role in vascular dysfunction is largely unknown. The aim of this study was to investigate whether activation of endothelial p53 has a pathological effect in relation to endothelial function. We established endothelial p53 loss-of-function and gain-of-function models by breeding endothelial-cell specific Cre mice with floxed Trp53 or floxed Mdm2/Mdm4 mice, respectively. Then we induced diabetes by injection of streptozotocin. In the diabetic state, endothelial p53 expression was markedly up-regulated and endothelium-dependent vasodilatation was significantly impaired. Impairment of vasodilatation was significantly ameliorated in endothelial p53 knockout (EC-p53 KO) mice, and deletion of endothelial p53 also significantly enhanced the induction of angiogenesis by ischemia. Conversely, activation of endothelial p53 by deleting Mdm2/Mdm4 reduced both endothelium-dependent vasodilatation and ischemia-induced angiogenesis. Introduction of p53 into human endothelial cells up-regulated the expression of phosphatase and tensin homolog (PTEN), thereby reducing phospho-eNOS levels. Consistent with these results, the beneficial impact of endothelial p53 deletion on endothelial function was attenuated in EC-p53 KO mice with an eNOS-deficient background. These results show that endothelial p53 negatively regulates endothelium-dependent vasodilatation and ischemia-induced angiogenesis, suggesting that inhibition of endothelial p53 could be a novel therapeutic target in patients with metabolic disorders.

The subcutaneous implantable cardioverter defibrillator (S-ICD) system was developed for defibrillation therapy that does not affect the heart and vasculature. S-ICD is preferred over transvenous ICD for patients with a history of recurrent infection presenting with life-threatening rhythms. Patients with bradycardia pacing indications are excluded from S-ICD therapy, as S-ICD lacks the capability of defibrillation in this patient group. Implantation of an S-ICD with a leadless pacemaker (LP) was proposed to overcome this issue. We describe the first case of successful implantation of S-ICD and LP in a Japanese patient with a history of recurrent prosthetic valve endocarditis.

【背景と目的】訪問看護師を対象に在宅心不全看護セミナー(以下、セミナー)を定期開催している。セミナーの目的は、心不全に関する知識の獲得やアセスメント能力を強化し、心不全の増悪徴候を早期発見できることである。しかし、受講後の評価やセミナーの内容改善のための現状が把握できていなかった。そこで、セミナー参加者へ質問紙による調査を行い、セミナーの評価をすること、およびセミナーの満足度やニーズから、内容改善について検討することとした。【方法】心不全に関する知識とアセスメント能力をウィルコクソンの符号付き順位検定にて比較し、セミナーへの満足度、ニーズ等は集計した。【結果】合計39名の訪問看護師が対象となり、受講前後で比較した心不全に関する知識、アセスメント能力の10項目全てで有意な上昇が認められた。自由記載の回答より、聴診や採血データ、フィジカルアセスメントの判断が不十分と感じる、演習の時間がもっと欲しい、心臓リハビリテーションや心エコー所見について知りたいなどのニーズが挙げられた。【考察と結論】本セミナー受講により心不全に関する知識の獲得やアセスメント能力が向上したと考えられた。様々な聴診の演習やフィジカルアセスメント、採血データの解釈、適切な水分量の把握など、より実践的な側面のニーズが明らかとなり、事例を交えながら講義や演習を行い、より実践的で活用可能な内容を盛り込む必要性が示唆された。(著者抄録)

BACKGROUND: The heart responds to hemodynamic overload through cardiac hypertrophy and activation of the fetal gene program. However, these changes have not been thoroughly examined in individual cardiomyocytes, and the relation between cardiomyocyte size and fetal gene expression remains elusive. We established a method of high-throughput single-molecule RNA imaging analysis of in vivo cardiomyocytes and determined spatial and temporal changes during the development of heart failure. METHODS AND RESULTS: We applied three novel single-cell analysis methods, namely, single-cell quantitative PCR (sc-qPCR), single-cell RNA sequencing (scRNA-seq), and single-molecule fluorescence in situ hybridization (smFISH). Isolated cardiomyocytes and cross sections from pressure overloaded murine hearts after transverse aortic constriction (TAC) were analyzed at an early hypertrophy stage (2 weeks, TAC2W) and at a late heart failure stage (8 weeks, TAC8W). Expression of myosin heavy chain β (Myh7), a representative fetal gene, was induced in some cardiomyocytes in TAC2W hearts and in more cardiomyocytes in TAC8W hearts. Expression levels of Myh7 varied considerably among cardiomyocytes. Myh7-expressing cardiomyocytes were significantly more abundant in the middle layer, compared with the inner or outer layers of TAC2W hearts, while such spatial differences were not observed in TAC8W hearts. Expression levels of Myh7 were inversely correlated with cardiomyocyte size and expression levels of mitochondria-related genes. CONCLUSIONS: We developed a new image-analysis pipeline to allow automated and unbiased quantification of gene expression at the single-cell level and determined the spatial and temporal regulation of heterogenous Myh7 expression in cardiomyocytes after pressure overload.

Significant recurrence of atrial tachyarrhythmias are observed after the surgical Cox Maze procedure (CMP). We retrospectively enrolled 11 consecutive patients who had atrial tachyarrhythmias (ATAs) that recurred after a biatrial CMP and underwent catheter ablation. Information including the site of any incomplete lesions and the etiology of the clinical ATAs was shared with the surgical team as feedback. In a total of 11 patients, 12 clinical ATAs were identified. They consisted of 2 atrial fibrillations and 10 atrial tachycardias (ATs). In 6 patients, the CMP was performed after the beginning of this investigation. In a total of 10 ATs, we diagnosed 5 mitral annular flutters, 2 roof-dependent flutters, 1 pulmonary vein (PV)-reentrant AT, and 1 localized reentrant AT. A total of 6 patients had reconnected perimitral block lines. PV reconnections were observed in 3 and posterior wall (PW) residual conduction was also observed in 3 cases. However, no residual conduction of the pulmonary vein isolation (PVI) and only 1 residual conduction of the PW were observed in 5 patients who underwent their index surgery after the beginning of this investigation. This fact may implicate that sharing the information from the electrophysiological study of postsurgical ATAs with the surgical team may contribute to the refinement of the CMP in each facility. <Learning objective: Reconduction of the surgical lesion is the major etiology of recurrence of atrial tachyarrhythmias after the surgical Cox Maze procedure. Although perimitral block line seemed to be the most frequent reconduction site, our study suggested that durable lesion of the PVI and the PW isolation could be achieved by improving surgical techniques by feedback from the electrophysiological team to the surgical team.>.

Nicorandil has vasodilatory effects on both the epicardial coronary arteries and the coronary microvasculature, thereby increasing coronary blood flow. The objective of the present study was to investigate the effectiveness of intravenous (IV) nicorandil infusion for fractional flow reserve (FFR) measurement. In this crossover randomized study, 49 patients underwent FFR measurement with a consecutive randomized order of patient-blind infusions of continuous IV adenosine administration and a single bolus IV administration of nicorandil. The primary endpoint was the difference between the FFR by nicorandil and the FFR by adenosine, as assessed by the Bland-Altman method. The mean FFR value measured by nicorandil was not significantly different from that measured by adenosine [0.8125 ± 0.1349 vs. 0.7978 ± 0.124; mean difference, 0.0147 (95% confidence interval - 0.0373, 0.0667); P = 0.58]. There was no clinically significant diagnostic discordance, with the FFR by nicorandil > 0.80 and that by adenosine < 0.75. Hyperemia was achieved earlier using nicorandil than adenosine (34 ± 13 vs. 58 ± 15, P < 0.001). The duration of hyperemia after IV nicorandil was variable (6-570 s, mean 89 ± 98 s). IV nicorandil decreased systolic blood pressure by 32 ± 16 mm Hg (24 ± 10%) from baseline. Linear regression analysis showed that the average FFR value and the difference in systolic blood pressure were significantly associated with the bias in the FFR value between the two drugs. In conclusions, the results of the present study suggest that IV nicorandil can achieve maximal hyperemia easily and rapidly, providing an acceptable diagnostic performance for FFR assessment. However, a wide range of variation in hyperemic plateau and a decrease in blood pressure are the major limitations of this method.