Background: Tobacco smoking is a leading preventable cause of morbidity and mortality worldwide; still, the success rate of smoking cessation is low in general. From the viewpoint of public health and clinical care, an objective biomarker of long-term smoking behavior is sought.
Methods and Results: This study assessed DNA methylation as a biomarker of smoking in a hospital setting through a combination of molecular approaches including genetic, DNA methylation and mRNA expression analyses. First, in an epigenome-wide association study involving Japanese individuals with chronic cardiovascular disease (n=94), genome-wide significant smoking association was identified at 2 CpG sites on chromosome 5, with the strongest signal at cg05575921 located in intron 3 of the aryl-hydrocarbon receptor repressor (AHRR) gene. Highly significant (P<1×10−27) smoking–cg05575921 association was validated in 2 additional panels (n=339 and n=300). For the relationship of cg05575921 methylation extent with time after smoking cessation and cumulative cigarette consumption among former smokers, smoking-related hypomethylation was found to remain for ≥20 years after smoking cessation and to be affected by multiple factors, such as cis-interaction of genetic variation. There was a significant inverse correlation (P=0.0005) between cg05575921 methylation extent and AHRR mRNA expression.
Conclusions: The present study results support that reversion of AHRR hypomethylation can be a quantifiable biomarker for progress in and observance of smoking cessation, although some methodological points need to be considered.
Circulation Journal Awards for the Year 2022
First Place in the Clinical Investigation Section
Background: It is still unclear whether changes in right ventricular function are associated with prognosis in heart failure (HF) patients. This study aimed to examine the prognostic effect of changes in right ventricular fractional area change (RVFAC).
Methods and Results: This study enrolled 480 hospitalized patients with decompensated HF, and measured RVFAC with echocardiography at discharge (first examination) and post-discharge in the outpatient setting (second examination). RVFAC was divided into 3 categories: >35% in 314 patients, 25–35% in 108 patients, and <25% in 58 patients. Next, based on changes in RVFAC from the first to the second examination, the patients were further classed into 4 groups: (1) Preserved/Unchanged (preserved and unchanged RVFAC, n=235); (2) Reduced/Improved (improved RVFAC in at least 1 category, n=106); (3) Reduced/Unchanged (reduced and unchanged RVFAC, n=47); and (4) Preserved or Reduced/Worsened (deteriorated RVAFC in at least 1 category, n=92). Multivariate logistic regression analysis revealed that chronic kidney disease and anemia were the predictors of the preserved or reduced/worsened RVFAC. In the Kaplan-Meier analysis, changes in RVFAC were associated with the cardiac event rate and all-cause mortality. In the multivariable Cox proportional hazard analysis, the preserved or reduced/worsened RVFAC was an independent predictor of cardiac events and all-cause mortality.
Conclusions: Changes in RVFAC were associated with post-discharge prognosis in hospitalized heart failure patients.
Circulation Journal Awards for the Year 2022
Second Place in the Clinical Investigation Section
Background: Dilated cardiomyopathy (DCM) associated with inflammation is diagnosed by endomyocardial biopsy; patients with this have a poorer prognosis than patients without inflammation. To date, standard diagnostic criteria have not been established.
Methods and Results: This study analyzed clinical records and endomyocardial biopsy samples of 261 patients with DCM (201 males, median left ventricular ejection fraction; 28%) from 8 institutions in a multicenter retrospective study. Based on the European Society of Cardiology criteria and CD3 (T-lymphocytes) and CD68 (macrophages) immunohistochemistry, 48% of patients were categorized as having inflammatory DCM. For risk-stratification, we divided patients into 3 groups using Akaike Information Criterion/log-rank tests, which can determine multiple cut-off points: CD3+-Low, <13/mm2(n=178, 68%); CD3+-Moderate, 13–24/mm2(n=58, 22%); and CD3+-High, ≥24/mm2(n=25, 10%). The survival curves for cardiac death or left ventricular assist device implantation differed significantly among the 3 groups (10-year survival rates: CD3+-Low: 83.4%; CD3+-Moderate: 68.4%; CD3+-High: 21.1%; Log-rank P<0.001). Multivariate Cox analysis revealed CD3+count as a potent independent predictive factor for survival (fully adjusted hazard ratio: CD3+-High: 5.70, P<0.001; CD3+-Moderate: 2.64, P<0.01). CD3+-High was also associated with poor left ventricular functional and morphological recovery at short-term follow up.
Conclusions: Myocardial CD3+T-lymphocyte infiltration has a significant prognostic impact in DCM and a 3-tiered risk-stratification model could be helpful to refine patient categorization.
Circulation Journal Awards for the Year 2022
Second Place in the Clinical Investigation Section
Background:The clinical significance of concomitant mitral regurgitation (MR) has not been well addressed in patients with severe aortic stenosis (AS).
Methods and Results:We analyzed 3,815 patients from a retrospective multicenter registry of severe AS in Japan (CURRENT AS registry). We compared the clinical outcomes between patients with moderate/severe MR and with none/mild MR according to the initial treatment strategy (initial aortic valve replacement [AVR] or conservative strategy). The primary outcome measure was a composite of aortic valve-related death or heart failure hospitalization. At baseline, moderate/severe MR was present in 227/1,197 (19%) patients with initial AVR strategy and in 536/2,618 (20%) patients with a conservative strategy. The crude cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with moderate/severe MR than in those with none/mild MR, regardless of the initial treatment strategy (25.2% vs. 14.4%, P<0.001 in the initial AVR strategy, and 63.3% vs. 40.7%, P<0.001 in the conservative strategy). After adjusting confounders, moderate/severe MR was not independently associated with higher risk for the primary outcome measure in the initial AVR strategy (hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.67–1.83, P=0.69), and in the conservative strategy (HR 1.13, 95% CI 0.93–1.37, P=0.22).
Conclusions:Concomitant moderate/severe MR was not independently associated with higher risk for the primary outcome measure regardless of the initial treatment strategy.
Circulation Journal Awards for the Year 2022
Second Place in the Clinical Investigation Section
Background:There is a gradual progression from paroxysmal to persistent atrial fibrillation (AF) in humans. To elucidate the mechanism involved, the creation of an artificial atrial substrate to persist AF in mice was attempted.
Methods and Results:This study used wild type (WT) mice, but it is difficult to induce AF in them. A novel antegrade perfusion method from the left ventricle (LV) to enlarge both atria for artificial atrial modification was proposed in this study. Short duration AF was induced by burst pacing under this method. Optical mapping analysis revealed non-sustained focal type and meandering spiral reentrants after short duration AF. A tiny artificial substrate (~1.2 mm in diameter) was added in by laser irradiation to create a critical atrial arrhythmogenic substrate. Burst pacing was performed in a non-laser group (n=8), a circular-shape laser group (n=8), and a wedge-shaped dent laser group (n=8). We defined AF and atrial tachycardia (AT) as atrial arrhythmia (AA). Long-lasting AA was defined as lasting for ≥30 min. Long-lasting AA was observed in 0/8, 0/8, and 6/8 (75%) mice in each group. Optical mapping analysis revealed that the mechanism was AT with a stationary rotor around the irradiated margin.
Conclusions:Regrettably, this study failed to reproduce persistent AF, but succeeded in creating an arrhythmic substrate that causes sustained AT in WT mice.
Circulation Journal Awards for the Year 2022
First Place in the Experimental Investigation Section
JCS/JHRS 2022 Guideline on Diagnosis and Risk Assessment of Arrhythmia
公開日: 2023/09/11 |
論文ID CJ-22-0827
Bonpei Takase, Takanori Ikeda, Wataru Shimizu, Haruhiko Abe, Takeshi Aiba, Masaomi Chinushi, Shinji Koba, Kengo Kusano, Shinichi Niwano, Naohiko Takahashi, Seiji Takatsuki, Kaoru Tanno, Eiichi Watanabe, Koichiro Yoshioka, Mari Amino, Tadashi Fujino, Yu-ki Iwasaki, Ritsuko Kohno, Toshio Kinoshita, Yasuo Kurita, Nobuyuki Masaki, Hiroshige Murata, Tetsuji Shinohara, Hirotaka Yada, Kenji Yodogawa, Takeshi Kimura, Takashi Kurita, Akihiko Nogami, Naokata Sumitomo, on behalf of the Japanese Circulation Society and Japanese Heart Rhythm Society Joint Working Group
Views: 3,196
JCS/JSCVS/JATS/JSVS 2020 Guideline on Diagnosis and Treatment of Aortic Aneurysm and Aortic Dissection
公開日: 2023/09/01 |
論文ID CJ-22-0794
Hitoshi Ogino, Osamu Iida, Koichi Akutsu, Yoshiro Chiba, Hiromitsu Hayashi, Hatsue Ishibashi-Ueda, Shuichiro Kaji, Masaaki Kato, Kimihiro Komori, Hitoshi Matsuda, Kenji Minatoya, Hiroko Morisaki, Takao Ohki, Yoshikatsu Saiki, Kunihiro Shigematsu, Norihiko Shiiya, Hideyuki Shimizu, Nobuyoshi Azuma, Hirooki Higami, Shigeo Ichihashi, Toru Iwahashi, Kentaro Kamiya, Takahiro Katsumata, Nobuyoshi Kawaharada, Yoshihisa Kinoshita, Takuya Matsumoto, Shinji Miyamoto, Takayuki Morisaki, Tetsuro Morota, Kiyonori Nanto, Toshiya Nishibe, Kenji Okada, Kazumasa Orihashi, Junichi Tazaki, Masanao Toma, Takuro Tsukube, Keiji Uchida, Tatsuo Ueda, Akihiko Usui, Kazuo Yamanaka, Haruo Yamauchi, Kunihiro Yoshioka, Takeshi Kimura, Tetsuro Miyata, Yutaka Okita, Minoru Ono, Yuichi Ueda, on behalf of the Japanese Circulation Society, the Japanese Society for Cardiovascular Surgery, the Japanese Association for Thoracic Surgery and the Japanese Society for Vascular Surgery Joint Working Group
Views: 3,046
Effects of Tobacco Smoking on Cardiovascular Disease
公開日: 2019/09/25 | 83 巻 10 号 p. 1980-1985
Takahisa Kondo, Yoshihisa Nakano, Shiro Adachi, Toyoaki Murohara
Views: 573
JCS 2023 Guideline on the Diagnosis and Treatment of Myocarditis
公開日: 2023/03/31 |
論文ID CJ-22-0696
Toshiyuki Nagai, Takayuki Inomata, Takashi Kohno, Takuma Sato, Atsushi Tada, Toru Kubo, Kazufumi Nakamura, Noriko Oyama-Manabe, Yoshihiko Ikeda, Takeo Fujino, Yasuhide Asaumi, Takahiro Okumura, Toshiyuki Yano, Kazuko Tajiri, Hiroyuki Matsuura, Yuichi Baba, Haruki Sunami, Shingo Tsujinaga, Yasutoshi Ota, Keiko Ohta-Ogo, Yusuke Ishikawa, Hideo Matama, Nobutaka Nagano, Kimi Sato, Kazushi Yasuda, Yasushi Sakata, Koichiro Kuwahara, Tohru Minamino, Minoru Ono, Toshihisa Anzai, on behalf of the Japanese Circulation Society Joint Working Group
Views: 453
JCS 2023 Guideline on the Diagnosis and Treatment of Myocarditis
公開日: 2023/04/25 | 87 巻 5 号 p. 674-754
Toshiyuki Nagai, Takayuki Inomata, Takashi Kohno, Takuma Sato, Atsushi Tada, Toru Kubo, Kazufumi Nakamura, Noriko Oyama-Manabe, Yoshihiko Ikeda, Takeo Fujino, Yasuhide Asaumi, Takahiro Okumura, Toshiyuki Yano, Kazuko Tajiri, Hiroyuki Matsuura, Yuichi Baba, Haruki Sunami, Shingo Tsujinaga, Yasutoshi Ota, Keiko Ohta-Ogo, Yusuke Ishikawa, Hideo Matama, Nobutaka Nagano, Kimi Sato, Kazushi Yasuda, Yasushi Sakata, Koichiro Kuwahara, Tohru Minamino, Minoru Ono, Toshihisa Anzai, on behalf of the Japanese Circulation Society Joint Working Group
Views: 398