Dual-single photon emission computed tomography and contrast-enhanced magnetic resonance imaging to evaluate dissimilar features of apical hypertrophic cardiomyopathy

Apical hypertrophic cardiomyopathy (HCM) is an uncommon variant of HCM characterized by hypertrophy located in the left ventricular apex that occurs at a rate of about 30% in the Japanese population. Although the prognosis of most patients with apical HCM is relatively benign, it can be poor if apical left ventricular aneurysms develop. However, the mechanism of aneurysmal formation is unclear. We describe two patients with apical HCM and dissimilar findings in 201Thallous chloride (201TlCl) and 123I-betamethyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP) dual single-photon emission computed tomography (dual-SPECT), but no myocardial fibrosis on contrast-enhanced magnetic resonance images (MRI). One had apparently normal myocardial perfusion and metabolism, whereas the other had exercise-induced myocardial ischemia and impaired myocardial metabolism. These findings indicated that even apical HCM without myocardial fibrosis is pathophysiologically heterogeneous. Apical HCM has been evaluated by either dual-SPECT or cardiac MRI, but not by both. Thus, a combination of imaging modalities is apparently essential for elucidating the pathophysiology of apical HCM. These dissimilar findings in dual-SPECT might be important in identifying patients with apical HCM who are at high risk of forming aneurysms. (Cardiol J 2010; 17, 3: 306-311

Cardiomyocyte Proliferative Capacity Is Restricted in Mice With Lmna Mutation

LMNA is one of the leading causative genes of genetically inherited dilated cardiomyopathy (DCM). Unlike most DCM-causative genes, which encode sarcomeric or sarcomere-related proteins, LMNA encodes nuclear envelope proteins, lamin A and C, and does not directly associate with contractile function. However, a mutation in this gene could lead to the development of DCM. The molecular mechanism of how LMNA mutation contributes to DCM development remains largely unclear and yet to be elucidated. The objective of this study was to clarify the mechanism of developing DCM caused by LMNA mutation.Methods and Results: We assessed cardiomyocyte phenotypes and characteristics focusing on cell cycle activity in mice with Lmna mutation. Both cell number and cell size were reduced, cardiomyocytes were immature, and cell cycle activity was retarded in Lmna mutant mice at both 5 weeks and 2 years of age. RNA-sequencing and pathway analysis revealed “proliferation of cells” had the most substantial impact on Lmna mutant mice. Cdkn1a, which encodes the cell cycle regulating protein p21, was strongly upregulated in Lmna mutants, and upregulation of p21 was confirmed by Western blot and immunostaining. DNA damage, which is known to upregulate Cdkn1a, was more abundantly detected in Lmna mutant mice. To assess the proliferative capacity of cardiomyocytes, the apex of the neonate mouse heart was resected, and recovery from the insult was observed. A restricted cardiomyocyte proliferating capacity after resecting the apex of the heart was observed in Lmna mutant mice.Conclusions: Our results strongly suggest that loss of lamin function contributes to impaired cell proliferation through cell cycle defects. The inadequate inborn or responsive cell proliferation capacity plays an essential role in developing DCM with LMNA mutation

低インスリン血症は、非糖尿病急性非代償性心不全患者において、全死亡、心血管死の独立した予後予測因子である

Background Insulin beneficially affects myocardial functions during myocardial ischemia. It increases glucose-derived ATP production, decreases oxygen consumption, suppresses apoptosis of cardiomyocytes, and promotes the survival of cardiomyocytes. Patients with chronic heart failure generally have high insulin resistance, which is correlated with poor outcomes. The role of insulin in acute decompensated heart failure (ADHF) remains unclear. This study aimed to investigate the prognostic value of serum insulin level at the time of admission for long-term outcomes in patients with ADHF. Methods and Results We enrolled 1074 consecutive patients who were admitted to our department for ADHF. Of these 1074 patients, we studied the impact of insulin on the prognosis of ADHF in 241 patients without diabetes mellitus. The patients were divided into groups according to low, intermediate, and high tertiles of serum insulin levels. Primary end points were all-cause death and cardiovascular death. During a mean follow-up of 21.8 months, 71 all-cause deaths and 38 cardiovascular deaths occurred. Kaplan-Meier analysis showed that all-cause and cardiovascular mortality was significantly higher in the low-insulin group than those in the intermediate- and high-insulin groups (log-rank P=0.0046 and P=0.038, respectively). Moreover, according to the multivariable analysis, low serum insulin was an independent predictor of all-cause and cardiovascular mortality (hazard ratio, 2.37 [95% CI, 1.24-4.65; P=0.009] and 2.94 [95% CI, 1.12-8.19; P=0.028], respectively). Conclusions Low serum insulin levels were associated with increased risk of all-cause and cardiovascular death in ADHF patients without diabetes mellitus.博士（医学）・甲第808号・令和4年3月15日© 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License(https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes

日本における非代償性急性心不全患者の30日および90日以内の心不全再入院の発生率と臨床的意義 : NARA-HF研究より

Background: Countermeasure development for early rehospitalization for heart failure (re-HHF) is an urgent and important issue in Western countries and Japan.Methods and Results:Of 1,074 consecutive NARA-HF study participants with acute decompensated HF admitted to hospital as an emergency between January 2007 and December 2016, we excluded 291 without follow-up data, who died in hospital, or who had previous HF-related hospitalizations, leaving 783 in the analysis. During the median follow-up period of 895 days, 241 patients were re-admitted for HF. The incidence of re-HHF was the highest within the first 30 days of discharge (3.3% [26 patients]) and remained high until 90 days, after which it decreased sharply. Within 90 days of discharge, 63 (8.0%) patients were re-admitted. Kaplan-Meier analysis revealed that patients with 90-day re-HHF had worse prognoses than those without 90-day re-HHF in terms of all-cause death (hazard ratio [HR] 2.321, 95% confidence interval [CI] 1.654-3.174; P<0.001) and cardiovascular death (HR 3.396, 95% CI 2.153-5.145; P<0.001). Multivariate analysis indicated that only male sex was an independent predictor of 90-day re-HHF. Conclusions: The incidence of early re-HHF was lower in Japan than in Western countries. Its predictors are not related to the clinical factors of HF, indicating that a new comprehensive approach might be needed to prevent early re-HHF.博士（医学）・甲第735号・令和2年3月16日日本循環器学会の許諾を得て登録（2020年9月2日付）ジャーナル公式サイト（日本循環器学会HP内）：https://www.j-circ.or.jp/journal/公開サイト（J-STAGE）：https://www.jstage.jst.go.jp/browse/circj

急性心不全における退院時の尿素窒素分画排泄率の予後判定への有用性

Background Maintaining euvolemia is crucial for improving prognosis in acute decompensated heart failure (ADHF). Although fractional excretion of urea nitrogen (FEUN) is used as a body fluid volume index in patients with acute kidney injury, the clinical impact of FEUN in patients with ADHF remains unclear. This study aimed to investigate whether FEUN can determine the long-term prognosis in patients with ADHF. Methods and Results We retrospectively identified 466 patients with ADHF who had FEUN measured at discharge between April 2011 and December 2018. The primary endpoint was post-discharge all-cause death. Patients were divided into two groups according to a FEUN cut-off value of 35%, commonly used in pre-renal failure. The FEUN <35% (low-FEUN) group included 224 patients (48.1%), and the all-cause mortality rate for the total cohort was 37.1%. The log-rank test revealed that the low-FEUN group had a significantly higher rate of all-cause death compared to the FEUN equal to or greater than 35% (high-FEUN) group (P<0.001). Multivariate Cox proportional hazards model analysis revealed that low-FEUN was associated with post-discharge all-cause death, independently of other heart failure risk factors (hazard ratio, 1.467; 95% CI, 1.030-2.088, P=0.033). The risk of low-FEUN compared to high-FEUN in post-discharge all-cause death was consistent across all subgroups; however, the effects tended to be modified by renal function (threshold: 60 mL/min/1.73 m2, interaction P=0.069). Conclusions Our study suggests that FEUN may be a novel surrogate marker of volume status in patients with ADHF requiring diuretics.博士（医学）・甲第814号・令和4年3月15日Copyright © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License(https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made

Percutaneous coronary intervention strategy for acute coronary syndrome caused by spontaneous coronary artery dissection for relieving ongoing ischemia—Case series and literature review

AbstractAlthough spontaneous coronary artery dissection (SCAD) is one of the causes of acute coronary syndrome (ACS) or sudden cardiac death, its standard management, especially primary percutaneous coronary intervention (PCI) in ACS patients with ongoing ischemia, has not been established. We experienced three ACS patients with SCAD who were treated with a different strategy of primary PCI. Each PCI strategy led to different clinical and procedural results. We describe here such PCI strategies and results, and also discuss the literature regarding primary PCI strategies for SCAD-induced ACS patients with ongoing ischemia.<Learning objective: SCAD is a cause of ACS. However, the treatment strategy of primary PCI for SCAD has not been fully investigated. We used different PCI strategies for three SCAD patients with ongoing ischemia. Our case series suggested that plain old balloon angioplasty is an acceptable option to avoid coronary stenting because the majority of patients were young menstruating women. Coronary vasospasm might be associated with SCAD. Treatment with vasodilators could be a potential pharmacological option for avoiding recurrence of SCAD.

僧帽弁閉鎖不全症を伴うまたは伴わない非代償性急性心不全患者の予後に心房細動が与える影響

Background: Atrial fibrillation (AF) and mitral regurgitation (MR) are frequently combined in patients with heart failure (HF). However, the effect of AF on the prognosis of patients with HF and MR remains unknown. Methods and Results: We studied 867 patients (mean age 73 years; 42.7% female) with acute decompensated HF (ADHF) in the NARA-HF registry. Patients were divided into 4 groups based on the presence or absence of AF and MR at discharge. Patients with severe MR were excluded. The primary endpoint was the composite of cardiovascular (CV) death and HF-related readmission. During the median follow-up of 621 days, 398 patients (45.9%) reached the primary endpoint. In patients with MR, AF was associated with a higher incidence of the primary endpoint regardless of left ventricular function; however, in patients without MR, AF was not associated with CV events. Cox multivariate analyses showed that the incidence of CV events was significantly higher in patients with AF and MR than in patients with MR but without AF (hazard ratio 1.381, P=0.036). Similar findings were obtained in subgroup analysis of patients with AF and only mild MR. Conclusions: The present study demonstrated that AF is associated with poor prognosis in patients with ADHF with mild to moderate MR, but not in those without MR.博士（医学）・甲第799号・令和3年9月29日© 2021, THE JAPANESE CIRCULATION SOCIETY This article is licensed under a Creative Commons [Attribution-NonCommercial-NoDerivatives 4.0 International] license. https://creativecommons.org/licenses/by-nc-nd/4.0

病床あたりの循環器内科医数が急性心不全の院内死亡に与える影響

Background Little evidence is available about the number of cardiologists required for appropriate treatment of heart failure (HF). Our objective was to determine the association between the number of cardiologists per cardiology beds for treating patients with acute HF and in-hospital mortality. Methods and Results This was a cross-sectional study, and we used the Japanese Registry of All Cardiac and Vascular Diseases Diagnosis Procedure Combination discharge database. The data of patients with HF on emergency admission from April 1, 2012, to March 31, 2014, were extracted. The patients were categorized into 4 groups by the quartiles of the numbers of cardiologists per 50 cardiovascular beds (first group: median, 4.4 [interquartile range, 3.5-5.0]; second group: median, 6.7 [interquartile range, 6.5-7.5]; third group: median, 9.7 [interquartile range, 8.8-10.1]; and fourth group: median, 16.7 [interquartile range, 14.0-23.8]). Using multilevel mixed-effect logistics regression, we determined adjusted odds ratios for in-hospital mortality. We identified 154 290 patients with HF on emergency admissions. There were 29 626, 36 587, 46 451, and 41 626 patients in the first, second, third, and fourth groups, respectively. HF severity, on the basis of New York Heart Association classification, was similar in the 3 groups. Adjusted odds ratios (95% CIs) for in-hospital mortality were 0.92 (0.82-1.04; P=0.20), 0.82 (0.72-0.92; P<0.001), and 0.70 (0.61-0.80; P<0.001) for the second, third, and fourth groups, respectively. The proportion of medication used, including angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, β blockers, and mineralocorticoid receptor antagonists, was positively correlated to the number of cardiologists. Conclusions Patients hospitalized for HF in hospitals with larger numbers of cardiologists per cardiovascular beds had lower 30-day mortality.博士（医学）・甲第776号・令和3年3月15日Copyright © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License(https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes

入院初日の尿中好中球ゼラチナーゼ結合性リポカリンは急性心不全患者の重要な予後予測因子である

Background Urinary neutrophil gelatinase‐associated lipocalin (U‐NGAL) is an early predictor of acute kidney injury and adverse events in various diseases; however, in acute decompensated heart failure patients, its significance remains poorly understood. This study aimed to investigate the prognostic value of U‐NGAL on the first day of admission for the occurrence of acute kidney injury and long‐term outcomes in acute decompensated heart failure patients. Methods and Results We studied 260 acute decompensated heart failure patients admitted to our department between 2011 and 2014 by measuring U‐NGAL in 24‐hour urine samples collected on the first day of admission. Primary end points were all‐cause eath, cardiovascular death, and heart failure admission. Patients were divided into 2 groups according to their median U‐NGAL levels (32.5 μg/gCr). The high‐U‐NGAL group had a significantly higher occurrence of acute kidney injury during hospitalization than the low‐U‐NGAL group (P=0.0012). Kaplan‐Meier analysis revealed that the high‐U‐NGAL group exhibited a worse prognosis than the low‐U‐NGAL group in all‐cause death (hazard ratio 2.07; 95%CI 1.38‐3.12, P=0.0004), cardiovascular death (hazard ratio 2.29; 95%CI 1.28‐4.24, P=0.0052), and heart failure admission (hazard ratio 1.77; 95%CI 1.13‐2.77, P=0.0119). The addition of U‐NGAL to the estimated glomerular filtration rate significantly improved the predictive accuracy of all‐cause mortality (P=0.0083). Conclusions In acute decompensated heart failure patients, an elevated U‐NGAL level on the first day of admission was related to the development of clinical acute kidney injury and independently associated with poor prognosis.博士（医学）・甲第675号・平成29年11月24日Copyright & Usage: © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License(http://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes

胎盤増殖因子の可溶性Fms様チロシンキナーゼ-1に対する血中濃度比の上昇は安定冠動脈疾患患者における有害事象発症の予測因子である

OBJECTIVE: To investigate the predictive values of placental growth factor (PlGF) and its endogenous antagonist, soluble fms-like tyrosine kinase-1 (sFlt-1), for the long-term prognosis of patients with stable coronary artery disease (CAD). Both PlGF and sFlt-1 play important roles in the pathological mechanisms of atherosclerosis. We recently demonstrated that the plasma levels of these molecules are correlated with the severity of coronary atherosclerosis. METHODS: We enrolled 464 patients with stable CAD who consecutively underwent coronary angiography. Baseline blood samples were collected from the femoral artery immediately before coronary angiography (after the administration of 20 units of heparin), and the plasma levels of PlGF and sFlt-1 were measured. A Cox proportional hazard regression analysis was performed to evaluate the relationship between these parameters and the occurrence of all-cause death (ACD) and total cardiovascular events (TCVE) during a median follow-up of 3.3 years. RESULTS: A total of 31 ACDs and 51 TCVEs occurred. Patients with higher PlGF/sFlt-1 ratios (>4.22×10(-2)) had a significantly higher risk of both ACD and TCVE than patients with lower ratios (<4.22×10(-2)) (hazard ratio [HR]: 3.32, 95% confidence interval [CI]: 1.43 to 7.72, p=0.005, and HR: 2.23, 95% CI: 1.23 to 4.03, p=0.008, respectively). A multivariate analysis showed the PlGF/sFlt-1 ratio to be an independent predictor for ACD, but not TCVE.博士（医学）・甲615号・平成26年3月17日発行元の規定により、本文の登録不可。本文は以下のURLを参照 "http://dx.doi.org/10.2169/internalmedicine.52.9073