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Soshiro Ogata, Kyohei Marume, Michikazu Nakai, Ryota Kaichi, Masanobu Ishii, Sou Ikebe, Takayuki Mori, Soichi Komaki, Hiroaki Kusaka, Reiko Toida, et al.
Published: 12 June 2021
Circulation Journal; doi:10.1253/circj.cj-20-1207

The publisher has not yet granted permission to display this abstract.
Tomonori Itoh, Nozomu Toda, Michiko Yoshizawa, Takuya Osaki, Yuko Maegawa, Reisuke Yoshizawa, Yu Ishikawa, Osamu Nishiyama, Satoshi Nakajima, Motoyuki Nakamura, et al.
Published: 12 June 2021
Circulation Journal; doi:10.1253/circj.cj-20-1044

The publisher has not yet granted permission to display this abstract.
Shunsuke Kawamoto
Published: 12 June 2021
Circulation Journal; doi:10.1253/circj.cj-21-0407

Xiao-Bing Wang, Fan-Xin Kong, Guan Wang, Yong-Huai Wang, Chun-Yan Ma
Published: 11 June 2021
Circulation Journal; doi:10.1253/circj.cj-21-0251

Keisuke Kida, Miho Nishitani-Yokoyama, Shogo Oishi, Yuji Kono, Kentaro Kamiya, Takuya Kishi, Koichi Node, Shigeru Makita, Yutaka Kimura, for the Japanese Association of Cardiac Rehabilitation (JACR) Public Relations Committee
Circulation Reports, Volume 3, pp 311-315; doi:10.1253/circrep.cr-21-0042

Abstract:
Background:Since the reporting of a cluster outbreak of coronavirus disease 2019 (COVID-19) in sports gyms, the Japanese Association of Cardiac Rehabilitation (CR) shared a common understanding of the importance of preventing patients and healthcare providers from contracting COVID-19. This questionnaire survey aimed to clarify the status of CR in Japan during the COVID-19 outbreak. Methods and Results:An online questionnaire survey was conducted in 37 Japanese CR training facilities after the national declaration of a state of emergency in 7 prefectures. Among these facilities, 70% suspended group ambulatory CR and 43% suspended cardiopulmonary exercise testing (CPX). In contrast, all facilities maintained individual inpatient CR. Of the 37 facilities, 95% required CR staff to wear a surgical mask during CR. In contrast, 50% of facilities did not require patients to wear a surgical mask during CR. Cardiac telerehabilitation was only conducted by a limited number of facilities (8%), because this method was still under development. In our survey, 30% of the facilities not providing cardiac telerehabilitation had specific plans for its future use. Conclusions:Our data demonstrate that ambulatory CR and CPX were suspended to avoid the spread of COVID-19. In the future, we need to consider CR resumption and develop new technologies for cardiovascular patients, including cardiac telerehabilitation.
Takuya Tsujimura, , Osamu Iida, Yosuke Hata, Taku Toyoshima, Naoko Higashino, Naoya Kurata, Mitsutoshi Asai, Masaharu Masuda, Shin Okamoto, et al.
Circulation Reports, Volume 3, pp 316-323; doi:10.1253/circrep.cr-21-0053

Abstract:
Background:The OrsiroTMultrathin-strut, biodegradable-polymer, sirolimus-eluting stent (O-SES) has specific characteristics regarding its components and has demonstrated comparable clinical outcomes compared with durable-polymer, drug-eluting stents (DES). However, arterial repair following deployment of the O-SES has not been elucidated to date. Methods and Results:Using data from the Kansai Rosai Hospital database between November 2010 and September 2020, we analyzed coronary angioscopy (CAS) findings a mean (±SD) of 10±2 months after implantation of an O-SES, a durable-polymer everolimus-eluting stent (XienceTM; X-EES), or a biodegradable-polymer everolimus-eluting stent (SynergyTM; S-EES). Neointimal coverage (NIC), yellow color intensity of the stented segment, and the incidence of thrombus adhesion were compared between the O-SES (66 stents from 42 patients), X-EES (119 stents from 87 patients), and S-EES (132 stents from 88 patients). NIC was significantly thinner for the O-SES than S-EES (P<0.001), but was similar between the O-SES and X-EES (P=0.25). Yellow color intensity was significantly greater for the O-SES than X-EES (P<0.001), but similar between the O-SES and S-EES (P=0.51). The incidence of thrombus adhesions was similar in all 3 groups. Conclusions:O-SES and X-EES resulted in similar inhibition of NIC and both resulted in a thinner NIC than with S-EES. In addition, O-SES exhibited a similar degree of thrombus adhesion as the other DES, suggesting similar thrombogenicity.
Yu Kawada, , Kenta Hachiya, Marina Kato, Kosuke Nakasuka, Shohei Kikuchi, Yoshihiro Seo, Nobuyuki Ohte
Circulation Reports, Volume 3, pp 345-353; doi:10.1253/circrep.cr-21-0011

Abstract:
Background:Risk stratification of normal-flow, low-gradient (NFLG) severe aortic stenosis (SAS) with preserved left ventricular (LV) ejection fraction (EF) remains unclear. Methods and Results:Of 289 consecutive patients diagnosed with SAS by aortic valve area 35 mL/m2, mean pressure gradient <40 mmHg, LVEF ≥50%) were enrolled in this study; patients with bicuspid aortic valve, acute coronary syndrome, hemodialysis, or a history of aortic valve replacement (AVR) were excluded. Adverse events (AEs) were defined as cardiovascular death, hospitalization for heart failure, and deteriorating condition requiring AVR. Factors associated with AEs were investigated using a Cox proportional hazards model. Over a median of 675 days of follow-up, 25 AEs were recorded: 4 cardiovascular deaths, 12 hospitalizations for heart failure, and 9 patients requiring AVR. In addition, there were 14 events of progression to high-gradient SAS. Multivariable analysis showed significant associations between AEs and the presence of symptoms (hazard ratio [HR] 10.276; 95% confidence interval [CI] 3.724–28.357; P115 and >95 mg/m2for males and females, respectively; HR 3.257; 95% CI 1.172–9.050; P=0.024), and tricuspid regurgitation (TR) velocity (HR 2.761; 95% CI 1.246–6.118; P=0.012). Conclusions:The presence of symptoms, LV hypertrophy, and high TR velocity could be reliable prognostic indicators and may require watchful waiting for timely AVR in patients with NFLG-SAS.
, Toshio Honda, Masataka Murakami, Fuminori Shinozuka, Kazuhiko Sadamoto, Yusuke Akazawa, Takashi Higaki, Osamu Yamaguchi
Circulation Reports, Volume 3, pp 356-357; doi:10.1253/circrep.cr-21-0052

Michihiro Kono, Yuka Shimizu
Circulation Reports, Volume 3, pp 354-355; doi:10.1253/circrep.cr-21-0023

Akira Oshima, Teruhiko Imamura, Nikhil Narang, Koichiro Kinugawa
Circulation Reports, Volume 3, pp 333-337; doi:10.1253/circrep.cr-21-0024

Abstract:
Background:The effects of mineralocorticoid receptor antagonists, including the newly introduced esaxerenone, on renal function remain uncertain. Methods and Results:This retrospective study was performed on patients who received esaxerenone for resistant hypertension between November 2019 and June 2020. Trends in the estimated glomerular filtration rate (eGFR) were compared between the 6-month period before esaxerenone treatment (pre-treatment period) and the 6-month treatment period on esaxerenone. Twenty-six patients (15 men), with a median age of 70 years (interquartile range [IQR] 51–73 years) and a median systolic blood pressure of 146 mmHg (IQR 139–156 mmHg), were included in the study and completed 6 months of esaxerenone therapy without any adverse events. eGFR decreased significantly during the pre-treatment period (from 66.6 to 59.5 mL/min/1.73 m2; P=0.003), whereas eGFR was unchanged during the treatment period (from 59.5 to 61.8 mL/min/1.73 m2; P=0.15). The median change in eGFR differed significantly between the treatment and pre-treatment periods (3.8 [IQR −4.2, 6.8] vs. −6.1 [IQR −11.1, 1.8] mL/min/1.73 m2, respectively; P=0.008). Conclusions:Esaxerenone may have renoprotective effects when administered to treat hypertension. Further studies are needed to understand which patient populations may see greater renoprotective benefits with esaxerenone.
Circulation Reports, Volume 3; doi:10.1253/circrep.cr-3-content6

Akihiro Shirakabe, Masato Matsushita, Fumitaka Okajima, Kuniya Asai, Wataru Shimizu
Circulation Reports, Volume 3, pp 359-359; doi:10.1253/circrep.cr-21-0048

Kenta Sugiura, Hiroki Kozuki, Hiroaki Ueba, Toru Kubo, Yuri Ochi, Yuichi Baba, Kazuya Miyagawa, Tatsuya Noguchi, Takayoshi Hirota, Naohito Yamasaki, et al.
Circulation Reports, Volume 3, pp 338-344; doi:10.1253/circrep.cr-21-0046

Abstract:
Background:Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) is a life-threatening progressive disease. Recent studies have shown that the detection of transthyretin (TTR) amyloid in tenosynovial tissue may play an important role in the diagnosis of cardiac amyloidosis. The aim of this study was to determine the prevalence of TTR amyloid deposits in surgical tissue of patients undergoing carpal tunnel surgery and to clarify the clinical significance of concomitant cardiac examination with 99 mTc-labeled pyrophosphate (99 mTc-PYP) scintigraphy in those patients with TTR deposition. Methods and Results:We evaluated 79 consecutive patients undergoing carpal tunnel release surgery and biopsy of tenosynovial tissue. The mean (±SD) age of the patients at surgery was 71.6±12.5 years (range 30–95 years); 32 patients (41%) were male. TTR amyloid deposition in tenosynovial tissue was observed in 27 patients (34%). Sixteen of those 27 patients underwent 99 mTc-PYP scintigraphy. Of those 16 patients, 3 (19%) had Grade 2 uptake on 99 mTc-PYP scintigraphy. None of the 3 patients with a diagnosis of ATTRwt-CA had apparent cardiac symptoms and left ventricular wall thickness >13 mm. Conclusions:Concomitant cardiac examination with 99 mTc-PYP scintigraphy in patients who had TTR amyloid deposition in tenosynovial tissue resulted in the identification of 19% of patients with a diagnosis of ATTRwt-CA. This diagnostic approach seems to be useful for the early diagnosis of the disease.
Hajime Kataoka
Circulation Reports, Volume 3, pp 324-332; doi:10.1253/circrep.cr-21-0005

Abstract:
Background:The mechanism underlying serum creatinine (SCr) fluctuations in heart failure (HF) patients remains unclear. This study examined mediators of SCr fluctuations under diuretic treatment in HF patients. Methods and Results:Data from 26 HF patients were analyzed. Clinical tests included measurement of peripheral blood, blood urea nitrogen, SCr, serum and urinary electrolytes, B-type natriuretic peptide (BNP), and plasma neurohormones. Among the 26 patients recovering from worsening HF, changes in SCr were negatively correlated with changes in serum Cl, and positively correlated with changes in plasma arginine vasopressin (AVP). According to the median change in SCr, patients were divided into high (range 0.16–0.79 mg/dL; n=13) and low (range −0.35 to 0.14 mg/dL; n=13) change groups. Plasma AVP concentrations after treatment decreased in the low SCr change group and increased in the high SCr change group (−1.28±2.8 vs. 2.14±4.4 pg/mL, respectively; P=0.027). In both groups, there was no change in plasma volume, plasma BNP and norepinephrine concentrations decreased, and plasma renin activity increased after treatment. Multivariate logistic regression analysis showed a tendency towards an independent association between an increase in SCr and an increase or no change in the plasma AVP after decongestion (odds ratio 4.44; 95% confidence interval 0.81–24.3; P=0.086). Conclusions:Plasma AVP appears to be a physiologically important mediator of SCr fluctuations under decongestion treatment in HF patients.
, Takashi Uchiyama, Nobuhiro Tanaka, Takaaki Ohkawauchi, Shunsuke Miwa, Nobuhiro Hijikata, Yuichi Kobori, Hitoshi Matsuo, Kiyotaka Iwasaki
Circulation Reports, Volume 3, pp 360-360; doi:10.1253/circrep.cr-66-0008

Abstract:
[This corrects the article DOI: 10.1253/circrep.CR-20-0099.].
Satomi Sakurai, Yoshifumi Ukyo
Circulation Reports; doi:10.1253/circrep.cr-21-0034

Abstract:
Background:Macitentan, an endothelin-receptor antagonist, is approved in Japan for the treatment of pulmonary arterial hypertension (PAH). This study evaluated the use of macitentan for chronic thromboembolic pulmonary hypertension (CTEPH) in Japanese patients. Methods and Results:This open-label single-arm Phase 3 study evaluated the efficacy and safety of oral macitentan 10 mg (once daily) in Japanese CTEPH patients. The study was prematurely discontinued due to the sponsor’s decision to not develop macitentan 10 mg further for the indication of CTEPH (unrelated to safety concerns). Of the 9 patients enrolled in the study, 4 completed 24 weeks of treatment. The mean (±SD) ratio of pulmonary vascular resistance (PVR) at Week 16 to baseline was 71.9±34.3%. The mean (±SD) decreases in PVR and the PVR index (PVRI) from baseline to Week 16 were 181.4±243.9 dyn·s/cm5and 280.6±366.0 dyn·s·m2/cm5, respectively. The mean (±SD) increase in the 6-min walk distance from baseline to Week 24 was 44.3±46.8 m. All treatment-emergent adverse events (TEAEs) were mild or moderate in severity, except for 1 serious TEAE of angioplasty reported in 1/9 patients that was severe in intensity. Conclusions:Definite conclusions regarding the efficacy of macitentan 10 mg in Japanese patients with CTEPH cannot be drawn because of premature study discontinuation. No safety concerns were observed, and the safety profile was consistent with previously reported studies in CTEPH and PAH patients.
Lusha W. Liang, Yuichi J. Shimada
Circulation Journal; doi:10.1253/circj.cj-21-0349

Abstract:
Endotyping is an emerging concept in which diseases are classified into distinct subtypes based on underlying molecular mechanisms. Heart failure (HF) is a complex clinical syndrome that encompasses multiple endotypes with differential risks of adverse events, and varying responses to treatment. Identifying these distinct endotypes requires molecular-level investigation involving multi-“omics” approaches, including genomics, transcriptomics, proteomics, and metabolomics. The derivation of these HF endotypes has important implications in promoting individualized treatment and facilitating more targeted selection of patients for clinical trials, as well as in potentially revealing new pathways of disease that may serve as therapeutic targets. One challenge in the integrated analysis of high-throughput omics and detailed clinical data is that it requires the ability to handle “big data”, a task for which machine learning is well suited. In particular, unsupervised machine learning has the ability to uncover novel endotypes of disease in an unbiased approach. In this review, we will discuss recent efforts to identify HF endotypes and cover approaches involving proteomics, transcriptomics, and genomics, with a focus on machine-learning methods.
Wen-Han Cheng, Yi-Hsin Chan, Jo-Nan Liao, Ling Kuo, Shih-Ann Chen, Tze-Fan Chao
Circulation Journal; doi:10.1253/circj.cj-21-0399

Abstract:
Stroke prevention is the cornerstone of management of atrial fibrillation (AF), and non-vitamin K antagonist oral anticoagulants (NOACs) are commonly prescribed. Because routine monitoring of anticoagulant effects of NOACs is not necessary, appropriate dosing following the criteria of each NOACs defined in pivotal randomized trials is important. Real-world data demonstrate that underdosing NOACs is associated with a higher risk of ischemic stroke without a lower risk of major bleeding. Furthermore, renal function of AF patients should be assessed using the Cockcroft-Gault formula to prevent overestimation that could result in overdosing of NOACs. The assessment of bleeding risk is important, and the HAS-BLED score should be used to help identify patients at high risk of bleeding (HAS-BLED score ≥3). Moreover, the HAS-BLED score should be reassessed at periodic intervals to address potentially modifiable bleeding risk factors because bleeding risks of AF patients are not static. When managing NOAC-related bleeding episodes, the possibility of occult malignancies (e.g., grastrointestinal [GI] tract cancers for patients experiencing GI bleeding and bladder cancer for patients with hematuria) should be kept in mind. Addressing all of these issues is crucial to achieving better clinical outcomes for anticoagulated AF patients. More efforts are necessary to incorporate clear and easy-to-follow recommendations about optimal management of anticoagulation into the guidelines to improve AF patient care.
Byung Joo Sun, Jae-Hyeong Park
Circulation Journal; doi:10.1253/circj.cj-21-0373

Abstract:
Unlike the left ventricle (LV), the left atrium (LA) has a thin-walled structure and has been regarded as a simple conduit chamber. However, the unique function of the LA to modulate LV filling has recently drawn much attention. Because LA structure and function are directly influenced by the LV filling pressure, LA assessment is an essential step in the diagnosis of diastolic dysfunction that can help predict new-onset atrial fibrillation, assess the risk of further embolic events, and identify high-risk patients for adverse cardiovascular events. Even in the recent era of multimodality imaging, 2-dimensional (2D) echocardiography is the most common imaging method and the central modality for evaluation of LA function. LA strain derived from 2D echocardiography can help assess LA function objectively and demonstrates the 3 distinct phasic motions of the LA cycle. Further, LA strain provides invaluable pathophysiologic information and helps to predict clinical prognosis in various cardiovascular diseases. In this review article, we focus on LA strain: basic concepts, advantages over conventional parameters, and some unresolved issues. Additionally, we present a brief history of the clinical evidence for LA strain. Through this review, we suggest echocardiography for LA strain assessment in clinical practice.
Hiroyuki Omori, Hideaki Ota, Takuya Mizukami, Yoshiaki Kawase, Toru Tanigaki, Tetsuo Hirata, Munenori Okubo, Masanori Kawasaki, Hitoshi Matsuo
Circulation Journal; doi:10.1253/circj.cj-21-0211

Thien Vu, Akira Fujiyoshi, Takashi Hisamatsu, Aya Kadota, Maryam Zaid, Hiroyoshi Segawa, Keiko Kondo, Sayuki Torii, Yoshihisa Nakagawa, Tomoaki Suzuki, et al.
Circulation Journal; doi:10.1253/circj.cj-20-1090

Abstract:
Background:Risk factors for atherosclerotic disease including dyslipidemia have been shown to be associated with aortic valve calcification (AVC). Nuclear magnetic resonance (NMR)-measured lipoprotein particles, low-density and high-density lipoprotein particles (LDL-p, HDL-p) in particular, have emerged as novel markers of atherosclerotic disease; however, whether NMR-measured particles are associated with AVC remains to be determined. This study aimed to examine the association between NMR-based lipoprotein particle measurements and standard lipids with AVC. The primary variables of interest were LDL-p (nmol/L), HDL-p (μmol/L), LDL-cholesterol, and HDL-cholesterol (both in mg/dL). Methods and Results:A community-based random sample of Japanese men aged 40–79 years examined in 2006–2008, in Shiga, Japan was studied. Presence of AVC was defined as an Agatston score >0. Lipoprotein particles were measured using NMR spectroscopy. In the main analysis, multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for the prevalence of AVC across the higher quartiles of lipids in reference to the lowest ones were obtained. Of 874 participants analyzed, 153 men had AVC. Multivariable-adjusted ORs of prevalent AVC for the highest vs. the lowest quartile were significantly elevated for LDL-p (OR, 2.20; 95% CI: 1.23–3.93) and LDL-cholesterol (OR, 2.16; 95% CI: 1.23–3.78). In contrast, neither HDL-p nor HDL-cholesterol was associated with AVC. Conclusions:The association of prevalent AVC with NMR-based LDL-p was comparable to that with LDL-cholesterol.
Yousuke Hashimoto, Yukio Ozaki, Shino Kan, Koichi Nakao, Kazuo Kimura, Junya Ako, Teruo Noguchi, Satoru Suwa, Kazuteru Fujimoto, Kazuoki Dai, et al.
Circulation Journal; doi:10.1253/circj.cj-20-1115

Abstract:
Background:The impact of chronic kidney disease (CKD) on long-term outcomes following acute myocardial infarction (AMI) in the era of modern primary PCI with optimal medical therapy is still in debate. Methods and Results:A total of 3,281 patients with AMI were enrolled in the J-MINUET registry, with primary PCI of 93.1% in STEMI. CKD stage on admission was classified into: no CKD (eGFR ≥60 mL/min/1.73 m2); moderate CKD (60>eGFR≥30 mL/min/1.73 m2); and severe CKD (eGFR <30 mL/min/1.73 m2). While the primary endpoint was all-cause mortality, the secondary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause death, cardiac failure, myocardial infarction (MI) and stroke. Of the 3,281 patients, 1,878 had no CKD, 1,073 had moderate CKD and 330 had severe CKD. Pre-person-days age- and sex-adjusted in-hospital mortality significantly increased from 0.014% in no CKD through 0.042% in moderate CKD to 0.084% in severe CKD (P<0.0001). Three-year mortality and MACE significantly deteriorated from 5.09% and 15.8% in no CKD through 16.3% and 38.2% in moderate CKD to 36.7% and 57.9% in severe CKD, respectively (P<0.0001). C-index significantly increased from the basic model of 0.815 (0.788–0.841) to 0.831 (0.806–0.857), as well as 0.731 (0.708–0.755) to 0.740 (0.717–0.764) when adding CKD stage to the basic model in predicting 3-year mortality (P=0.013; net reclassification improvement [NRI] 0.486, P<0.0001) and MACE (P=0.046; NRI 0.331, P<0.0001) respectively. Conclusions:CKD remains a useful predictor of in-hospital and 3-year mortality as well as MACE after AMI in the modern PCI and optimal medical therapy era.
Riku Arai, Nobuhiro Murata, Akimasa Yamada, Suguru Migita, Yutaka Koyama, Tomoyuki Morikawa, Shingo Ihara, Naotaka Akutsu, Tsukasa Kuwana, Daisuke Fukamachi, et al.
Circulation Reports; doi:10.1253/circrep.cr-21-0055

Jeehoon Kang, Jung-Kyu Han, Han-Mo Yang, Kyung Woo Park, Hyun-Jae Kang, Hyeon-Cheol Gwon, Woo Jung Chun, Seung-Ho Hur, Seung Hwan Han, Seung-Woon Rha, et al.
Circulation Journal; doi:10.1253/circj.cj-20-0999

Abstract:
Background:It has not been determined which specific 2-stenting strategy is the best for bifurcation lesions. Our aim was to investigate the clinical outcomes of various 2-stenting strategies in the era of 2nd-generation drug-eluting stents (2G-DES). Methods and Results:We analyzed 454 patients who finally underwent 2-stenting for a bifurcation lesion, from among 2,648 patients enrolled in the COBIS III registry. The primary outcome was target lesion failure (TLF). Patients were analyzed according to stenting sequence (provisional [main vessel stenting first] vs. systemic [side branch stenting first]) and stenting technique (crush vs. T vs. culotte vs. kissing/V stenting). Overall, 4.4 years’ TLF after 2-stenting treatment for bifurcation lesion was excellent: TLF 11.2% and stent thrombosis 1.3%. There was no difference in TLF according to 2-stenting strategy (11.1% vs. 10.5%, P=0.990 for provisional and systemic sequence; 8.6% vs. 14.4% vs. 12.9% vs. 12.2%, P=0.326 for crush, T, culotte, kissing/V technique, respectively). Only left main (LM) disease and a shorter duration of dual antiplatelet therapy (DAPT) were associated with TLF. The distribution of DAPT duration differed between patients with and without TLF, and the time-point of intersection was 2.5 years. Also, the side branch was the most common site of restenosis. Conclusions:The stenting sequence or technique did not affect clinical outcomes, but LM disease and shorter DAPT were associated with TLF, in patients with bifurcation lesions undergoing 2-stenting with 2G-DES.
Masanobu Ishii, Kyohei Marume, Michikazu Nakai, Soshiro Ogata, Ryota Kaichi, Sou Ikebe, Takayuki Mori, Soichi Komaki, Hiroaki Kusaka, Reiko Toida, et al.
Circulation Journal; doi:10.1253/circj.cj-21-0071

Abstract:
Background:Cancer is a known prognostic factor in patients with acute coronary syndrome (ACS), but few risk assessments of cancer development after ACS have been established. Methods and Results:Of the 573 consecutive ACS admissions between January 2015 and March 2018 in Nobeoka City, Japan, 552 were analyzed. Prevalent cancer was defined as a treatment history of cancer, and incident cancer as post-discharge cancer incidence. The primary endpoint was post-discharge cancer incidence, and the secondary endpoint was all-cause death during follow-up. All-cause death occurred in 9 (23.1%) patients with prevalent cancer, and in 17 (3.5%) without cancer. In the multivariable analysis, prevalent cancer was associated with all-cause death. To develop the prediction model for cancer incidence, 21 patients with incident cancer and 492 without cancer were analyzed. We compared the performance of D-dimer with that of the prediction model, which added age (≥65 years), smoking history, and high red blood cell distribution width to albumin ratio (RAR) to D-dimer. The areas under the receiver-operating characteristics curves of D-dimer and the prediction model were 0.619 (95% confidence interval: 0.512–0.725) and 0.774 (0.676–0.873), respectively. Decision curve analysis showed superior net benefits of the prediction model. Conclusions:By adding elderly, smoking, and high RAR to D-dimer to the prediction model it became clinically useful for predicting cancer incidence after ACS.
Akihiko Nogami, Takashi Kurita, Haruhiko Abe, Kenji Ando, Toshiyuki Ishikawa, Katsuhiko Imai, Akihiko Usui, Kaoru Okishige, Kengo Kusano, Koichiro Kumagai, et al.
Circulation Journal; doi:10.1253/circj.cj-20-0637

Noriaki Iwahashi, Jin Kirigaya, Masaomi Gohbara, Takeru Abe, Mutsuo Horii, Yohei Hanajima, Noriko Toya, Hironori Takahashi, Yugo Minamimoto, Yuichiro Kimura, et al.
Circulation Journal; doi:10.1253/circj.cj-21-0183

Abstract:
Background:Three-dimensional (3D) speckle tracking echocardiography (STE) after ST-elevation acute myocardial infarction (STEMI) is associated with left ventricular (LV) remodeling and 1-year prognosis. This study investigated the clinical significance of 3D-STE in predicting the long-term prognosis of patients with STEMI. Methods and Results:A total of 270 patients (mean age 64.6 years) with first-time STEMI treated with reperfusion therapy were enrolled. At 24 h after admission, standard 2D echocardiography and 3D full-volume imaging were performed, and 2D-STE and 3D-STE were calculated. Patients were followed up for a median of 119 months (interquartile range: 96–129 months). The primary endpoint was occurrence of a major adverse cardiac event (MACE: cardiac death, heart failure with hospitalization), and 64 patients experienced MACEs. Receiver operating characteristic curves and Cox hazard multivariate analysis showed that the 3D-STE indices were stronger predictors of MACE compared with those of 2D-STE. Additionally, 3D-global longitudinal strain (GLS) was the strongest predictor for MACE followed by 3D-global circumferential strain (GCS). The Kaplan-Meier curve demonstrated that 3D-GLS >−11.0 was an independent predictor for MACE (log-rank χ2=132.2, P−18.3, patients with higher values of 3D-GLS and 3D-GCS were found to be at extremely high risk for MACE. Conclusions:Global strain measured by 3D-STE immediately after the onset of STEMI is a clinically significant predictor of 10-year prognosis.
Takafumi Okuyama, Tomonori Watanabe, Kenji Harada, Hiroaki Watanabe, Ayako Yokota, Masashi Kamioka, Takahiro Komori, Tomoyuki Kabutoya, Yasushi Imai, Kazuomi Kario
Circulation Journal; doi:10.1253/circj.cj-21-0121

Ji Seong Kim, Yoonjin Kang, Suk Ho Sohn, Ho Young Hwang, Jae Woong Choi, Kyung Hwan Kim
Circulation Journal; doi:10.1253/circj.cj-20-1193

Abstract:
Background:This study evaluated the long-term outcomes for up to 20 years after On-X mechanical valve implantation in the left side of the heart. Methods and Results:Between 1999 and 2015, 861 patients (mean age=51.6±10.9 years) who underwent prosthetic valve replacement using the On-X valve in the aortic or mitral position were enrolled (aortic=344, mitral=325, double=192). The mean clinical follow-up duration was 10.5±5.3 (median 10.9) years. Operative mortality occurred in 26 patients (3.0%), and linearized late cardiac mortality was 0.9%/patient-year without an intergroup difference. Linearized thromboembolism, bleeding, prosthetic valve endocarditis, non-structural valve deterioration (NSVD), and reoperation rates were 0.8%/patient-year, 0.6%/patient-year, 0.2%/patient-year, 0.5%/patient-year, and 0.5%/patient-year, respectively. Prosthetic valve endocarditis was more frequent after double valve replacement than after aortic or mitral valve replacement (P=0.008 and 0.005, respectively). NSVD and reoperation rates were significantly lower aortic valve replacement than after mitral or double valve replacement (P=0.001 and 0.002, P=0.001 and <0.001, respectively). Valve replacement in the mitral position was the only risk factor for NSVD (hazard ratio [95% confidence interval]=5.247 [1.608–17.116], P=0.006). Conclusions:On-X valve implantation in the left side heart had favorable clinical outcomes with acceptable early and late mortality and a low incidence of prosthetic valve-related complications. Particularly in the aortic position, the On-X valve had better long-term non-structural durability.
Saki Iwai, Makoto Watanabe, Akihiko Okamura, Atsushi Kyodo, Kazutaka Nogi, Daisuke Kamon, Yukihiro Hashimoto, Tomoya Ueda, Tsunenari Soeda, Hiroyuki Okura, et al.
Circulation Journal; doi:10.1253/circj.cj-20-1233

Abstract:
Background:Optical coherence tomography (OCT) has the potential to characterize the detailed morphology of calcified coronary plaques. This study examined the prognostic impact of calcified plaque morphology in patients with coronary artery calcification (CAC) who underwent newer-generation drug-eluting stent (DES) implantation. Methods and Results:In all, 251 patients with moderate to severe CAC who underwent OCT-guided DES implantation were reviewed retrospectively and divided into 3 groups according to OCT findings of the target lesion: 25 patients (10.0%) with calcified nodules (CN), 69 patients (27.5%) with calcified protrusion (CP) without CN, and 157 patients (62.5%) with superficial calcific sheet (SC) without CN and CP. The primary endpoint was major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, and target lesion revascularization (TLR). Kaplan-Meier survival analysis revealed that, among the 3 groups, the rates of MACE-free survival (log-rank test, P=0.0117), myocardial infarction (log-rank test, P=0.0103), and TLR (log-rank test, P=0.0455) were significantly worse in patients with CN. Multivariate Cox proportional hazards analysis demonstrated that CN was an independent predictor of MACE (hazard ratio 4.41; 95% confidence interval 1.63–10.8; P=0.0047). Conclusions:Target lesion CN was associated with higher cardiac event rates in patients who underwent newer-generation DES implantation for lesions with moderate to severe CAC.
Seiji Takatsuki
Circulation Journal; doi:10.1253/circj.cj-21-0274

Koki Fujimori, Ayako Okada, Hiroaki Tabata, Morio Shoda, Koichiro Kuwahara
Circulation Journal; doi:10.1253/circj.cj-21-0164

Masaya Kato, Keigo Dote, Noboru Oda, Aya Yamane, Michiaki Nagai, Eisuke Kagawa, Eiji Kunita, Noriyasu Fukushima, Tatsuo Ichinohe
Circulation Journal, Volume 85; doi:10.1253/circj.cj-21-0158

Brunon Tomasiewicz, Piotr Kubler, Wojciech Zimoch, Michał Kosowski, Wojciech Wańha, Szymon Ładziński, Oscar Rakotoarison, Andrzej Ochała, Wojciech Wojakowski, Krzysztof Reczuch
Circulation Journal, Volume 85, pp 867-876; doi:10.1253/circj.cj-20-1222

Abstract:
Background:The aim of the study was to assess anatomical and procedural predictors of clinical and procedural failure of rotational atherectomy (RA) in an all-comers population. Methods and Results:A total of 534 consecutive patients who underwent RA were included in a double-center observational study. The primary composite endpoint consisted of: rota-wire introduction failure, burr-passage failure, periprocedural complications and procedure-related major adverse events. The second primary endpoint included rota-wire introduction failure and burr-passage failure. The primary endpoint occurred in 76 (14.2%) patients and the second primary endpoint occurred in 64 (12%) Periprocedural complications occurred in 23 (4.3%) and procedure-related adverse events in 23 (4.3%) patients. Multivariable analysis revealed angulation on lesion ≤90° (HR=2.18, 95% CI: 1.21–3.94, P=0.0096) and sequential lesion (HR=1.89, 95% CI: 1.01–3.54, P=0.046) as independent predictors of no clinical success of RA. Multivariable analysis revealed again that angulation on lesion ≤90° (HR=2.26, 95% CI: 1.16–4.40, P=0.02) and sequential lesion (HR=3.77, 95% CI: 1.64–8.69, P<0.01) as independent predictors of no procedural success of RA. Conclusions:The presence of an acute angulation on lesion and sequential lesion are independent determinants of clinical and procedural failure of RA. Further research is necessary to establish a score predicting RA failure, which can help in preproceduralrisk stratification of patients undergoing complex percutaneous coronary intervention with RA.
Shinichi Goto, Genki Ichihara, Yoshinori Katsumata, Seien Ko, Atsushi Anzai, Kohsuke Shirakawa, Jin Endo, Masaharu Kataoka, Hidenori Moriyama, Takahiro Hiraide, et al.
Circulation Journal, Volume 85, pp 929-938; doi:10.1253/circj.cj-20-0783

Abstract:
Background:Timely differentiation of monocytes into M2-like macrophages is important in the cardiac healing process after myocardial infarction (MI), but molecular mechanisms governing M2-like macrophage differentiation at the transcriptional level after MI have not been fully understood. Methods and Results:A time-series microarray analysis of mRNAs and microRNAs in macrophages isolated from the infarcted myocardium was performed to identify the microRNAs involved in regulating the process of differentiation to M2-like macrophages. Correlation analysis revealed 7 microRNAs showing negative correlations with the progression of polarity changes towards M2-like subsets. Next, correlation coefficients for the changes in expression of mRNAs and miRNAs over time were calculated for all combinations. As a result, miR-27a-5p was extracted as a possible regulator of the largest number of genes in the pathway for the M2-like polarization. By selecting mouse mRNAs and human mRNAs possessing target sequences of miR-27a-5p and showing expression patterns inversely correlated with that of miR-27a-5p, 8 potential targets of miR-27a-5p were identified, includingPpm1l. Using the mouse bone marrow-derived macrophages undergoing differentiation into M2-like subsets by interleukin 4 stimulation, we confirmed that miR-27a-5p suppressed M2-related genes by negatively regulatingPpm1lexpression. Conclusions:Ppm1land miR-27a-5p may be the key molecules regulating M2-like polarization, with miR-27a-5p inhibiting the M2-like polarization through downregulation ofPpm1lexpression.
Jihoon Kim, Young Bin Song, Ju-Hyeon Oh, Deok-Kyu Cho, Jin Bae Lee, Sang-Hyun Kim, Jin-Ok Jeong, Jang-Ho Bae, Byung Ok Kim, Jang Hyun Cho, et al.
Circulation Journal, Volume 85, pp 817-825; doi:10.1253/circj.cj-20-0704

Abstract:
Background:The benefits and risks of prolonged dual antiplatelet therapy (DAPT) have not been studied extensively across a broad spectrum of acute coronary syndromes. In this study we investigated whether treatment effects of prolonged DAPT were consistent in patients presenting with ST-segment elevation myocardial infarction (STEMI) vs. non-STEMI (NSTEMI). Methods and Results:As a post hoc analysis of the SMART-DATE trial, effects of ≥12 vs. 6 months DAPT were compared among 1,023 patients presenting with STEMI and 853 NSTEMI patients. The primary outcome was a composite of recurrent myocardial infarction (MI) or stent thrombosis at 18 months after the index procedure. Compared with the 6-month DAPT group, the rate of the composite endpoint was significantly lower in the ≥12-month DAPT group (1.2% vs. 3.8%; hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.12–0.77; P=0.012). The treatment effect of ≥12- vs. 6-month DAPT on the composite endpoint was consistent among NSTEMI patients (0.2% vs. 1.2%, respectively; HR 0.20, 95% CI 0.02–1.70; P=0.140; Pinteraction=0.718). In addition, ≥12-month DAPT increased Bleeding Academic Research Consortium (BARC) Type 2–5 bleeding among both STEMI (4.4% vs. 2.0%; HR 2.18, 95% CI 1.03–4.60; P=0.041) and NSTEMI (5.1% vs. 2.2%; HR 2.37, 95% CI 1.08–5.17; P=0.031; Pinteraction=0.885) patients. Conclusions:Compared with 6-month DAPT, ≥12-month DAPT reduced recurrent MI or stent thrombosis regardless of the type of MI at presentation.
Akihiro Tobe, Akihito Tanaka, Yoshiyuki Tokuda, Sho Akita, Taro Fujii, Yusuke Miki, Kenji Furusawa, Hideki Ishii, Akihiko Usui, Toyoaki Murohara
Circulation Journal; doi:10.1253/circj.cj-21-0354

Abstract:
Background:The changes in electrocardiographic left ventricular hypertrophy (ECG-LVH) after transcatheter aortic valve implantation (TAVI) are not fully elucidated. Methods and Results:The study group included 64 patients who underwent TAVI for aortic stenosis. Their 12-lead ECGs before and at 2 days and 1, 6 and 12 months after TAVI were analyzed, and ECG-LVH was evaluated using various definitions. Values and prevalence of each ECG-LVH parameter significantly decreased between 1 and 6 months after TAVI. Values of ECG-LVH parameters decreased especially in patients with ECG-LVH at baseline. Conclusions:Regression of ECG-LVH was observed between 1 and 6 months after TAVI.
Circulation Journal, Volume 85; doi:10.1253/circj.cj-85-cover6

Yasuko K. Bando
Circulation Journal, Volume 85, pp 847-849; doi:10.1253/circj.cj-21-0174

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