Papers - KAIKITA Koichi
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Impact of cerebrovascular comorbidity on prognosis in Japanese patients undergoing PCI: 1-year data from Japanese multicenter registry (KICS). Reviewed
Ahmed K, Arima Y, Tabata N, Ishii M, Sato R, Yamashita T, Yamanaga K, Takizawa H, Hokimoto S, Sueta D, Araki S, Fujisue K, Takashio S, Fujimoto K, Shimomura H, Tsunoda R, Hirose T, Sato K, Kikuta K, Sakaino N, Nakamura S, Yamamoto N, Matsumura T, Kajiwara I, Tayama S, Sakamoto T, Nakao K, Oshima S, Yamamoto E, Sakamoto K, Kaikita K, Matsushita K, Tsujita K
Heart and vessels 37 ( 6 ) 911 - 918 2022.1
Language：English Publishing type：Research paper (scientific journal)
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Lotus Root-Like Appearance of a Lipid-Rich Plaque in a Patient With Acute Myocardial Infarction - Findings From Near-Infrared Spectroscopy and Optical Coherence Tomography. Reviewed
Nishihira K, Shibata Y, Kaikita K
Circulation reports 4 ( 1 ) 66 - 67 2022.1
Language：English Publishing type：Research paper (scientific journal)
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Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension. Reviewed
Hirakawa K, Yamamoto E, Takashio S, Hanatani S, Araki S, Suzuki S, Kaikita K, Matsushita K, Ogo T, Tsujita K
Cardiovascular intervention and therapeutics 37 ( 1 ) 60 - 65 2022.1
Language：English Publishing type：Research paper (scientific journal)
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HFA-PEFF scores: prognostic value in heart failure with preserved left ventricular ejection fraction. Reviewed
Egashira K, Sueta D, Komorita T, Yamamoto E, Usuku H, Tokitsu T, Fujisue K, Nishihara T, Oike F, Takae M, Hanatani S, Takashio S, Ito M, Yamanaga K, Araki S, Soejima H, Kaikita K, Matsushita K, Tsujita K
The Korean journal of internal medicine 37 ( 1 ) 96 - 108 2022.1
Language：English Publishing type：Research paper (scientific journal)
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Development of anti-thrombotic vaccine against human S100A9 in rhesus monkey Reviewed
Shimamura M., Kaikita K., Nakagami H., Kawano T., Ju N., Hayashi H., Nakamaru R., Yoshida S., Sasaki T., Mochizuki H., Tsujita K., Morishita R.
Scientific Reports 11 ( 1 ) 11472 2021.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports
In post-stroke patients, a decreased adherence to antiplatelet drugs is a major challenge in the prevention of recurrent stroke. Previously, we reported an antiplatelet vaccine against S100A9 in mice, but the use of Freund’s adjuvant and the difference in amino acid sequences in epitopes between mice and humans were problematic for clinical use. Here, we redesigned the S100A9 vaccine for the common sequence in both humans and monkeys and examined its effects in cynomolgus monkeys with Alum adjuvant. First, we assessed several candidate epitopes and selected 102 to 112 amino acids as the suitable epitope, which could produce antibodies. When this peptide vaccine was intradermally injected into 4 cynomolgus monkeys with Alum, the antibody against human S100A9 was successfully produced. Anti-thrombotic effects were shown in two monkeys in a mixture of vaccinated serum and fresh whole blood from another cynomolgus monkey. Additionally, the anti-thrombotic effects were partially inhibited by the epitope peptide, indicating the feasibility of neutralizing anti-thrombotic effects of produced antibodies. Prolongation of bleeding time was not observed in vaccinated monkeys. Although further studies on increasing the effect of vaccine and safety are necessary, this vaccine will be a promising approach to improve adherence to antiplatelet drugs in clinical settings.
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Sirt7 Deficiency Attenuates Neointimal Formation Following Vascular Injury by Modulating Vascular Smooth Muscle Cell Proliferation. Reviewed
Kimura Y, Izumiya Y, Araki S, Yamamura S, Hanatani S, Onoue Y, Ishida T, Arima Y, Nakamura T, Yamamoto E, Senokuchi T, Yoshizawa T, Sata M, Kim-Mitsuyama S, Nakagata N, Bober E, Braun T, Kaikita K, Yamagata K, Tsujita K
Circulation journal : official journal of the Japanese Circulation Society 85 ( 12 ) 2232 - 2240 2021.11
Language：English Publishing type：Research paper (scientific journal)
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Associations of cardiovascular risk factors with survival outcomes in a cancer registration: Findings from the KUMAMON registry. Reviewed
Maki Y, Sueta D, Ishii M, Yamanouchi Y, Fujisue K, Yamanaga K, Nakamura T, Tabata N, Arima Y, Araki S, Yamamoto E, Kaikita K, Chikamoto A, Matsushita K, Matsuoka M, Usuku K, Tsujita K
Medicine 100 ( 47 ) e27921 2021.11
Language：English Publishing type：Research paper (scientific journal)
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重症再生不良性貧血を合併した不安定狭心症に対し人工心肺非使用冠動脈バイパス術を施行した1例
廣田貴史, 定永達明, 高木淳, 西川幸作, 吉永隆, 岡本健, 海北幸一, 辻田賢一, 福井寿啓.
心臓 53 ( 11 ) 1213 - 1219 2021.11
Publishing type：Research paper (scientific journal)
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Rivaroxaban Monotherapy in Patients With Atrial Fibrillation After Coronary Stenting: Insights From the AFIRE Trial. Reviewed
Matoba T, Yasuda S, Kaikita K, Akao M, Ako J, Nakamura M, Miyauchi K, Hagiwara N, Kimura K, Hirayama A, Matsui K, Ogawa H, AFIRE Investigators.
JACC. Cardiovascular interventions 14 ( 21 ) 2330 - 2340 2021.11
Language：English Publishing type：Research paper (scientific journal)
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Aspirin versus P2Y<inf>12</inf>inhibitors with anticoagulation therapy for atrial fibrillation Reviewed
Fukaya H., Ako J., Yasuda S., Kaikita K., Akao M., Matoba T., Nakamra M., Miyauchi K., Hagiwara N., Kimura K., Hirayama A., Matsui K., Ogawa H.
Heart 107 ( 21 ) 1731 - 1738 2021.11
Language：English Publishing type：Research paper (scientific journal) Publisher：Heart
Objective: Patients with coronary artery disease (CAD) and atrial fibrillation (AF) can be treated with multiple antithrombotic therapies including antiplatelet and anticoagulant therapies; however, this has the potential to increase bleeding risk. Here, we aimed to evaluate the efficacy and safety of P2Y12 inhibitors and aspirin in patients also receiving anticoagulant therapy. Methods: We evaluated patients from the Atrial Fibrillation and Ischaemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial who received rivaroxaban plus an antiplatelet agent; the choice of antiplatelet agent was left to the physician's discretion. The primary efficacy and safety end points, consistent with those of the AFIRE trial, were compared between P2Y12 inhibitors and aspirin groups. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularisation or death from any cause. The primary safety end point was major bleeding according to the International Society on Thrombosis and Haemostasis criteria. Results: A total of 1075 patients were included (P2Y12 inhibitor group, n=297; aspirin group, n=778). Approximately 60% of patients were administered proton pump inhibitors (PPIs) and there was no significant difference in PPI use in the groups. There were no significant differences in the primary end points between the groups (efficacy: HR 1.31; 95% CI 0.88 to 1.94; p=0.178; safety: HR 0.79; 95% CI 0.43 to 1.47; p=0.456). Conclusions: There were no significant differences in cardiovascular and bleeding events in patients with AF and stable CAD taking rivaroxaban with P2Y12 inhibitors or aspirin in the chronic phase. Trial registration number: UMIN000016612; NCT02642419.
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Clinical Outcomes of Rivaroxaban Monotherapy in Heart Failure Patients With Atrial Fibrillation and Stable Coronary Disease: Insights From the AFIRE Trial. Reviewed
Yazaki Y, Nakamura M, Iijima R, Yasuda S, Kaikita K, Akao M, Ako J, Matoba T, Miyauchi K, Hagiwara N, Kimura K, Hirayama A, Matsui K, Ogawa H, AFIRE Investigators.
Circulation 144 ( 17 ) 1449 - 1451 2021.10
Language：English Publishing type：Research paper (scientific journal)
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Ishii M., Seki T., Kaikita K., Sakamoto K., Nakai M., Sumita Y., Nishimura K., Miyamoto Y., Noguchi T., Yasuda S., Kanaoka K., Terasaki S., Saito Y., Tsutsui H., Komuro I., Ogawa H., Tsujita K., Kawakami K.
European Journal of Preventive Cardiology 28 ( 13 ) 1435 - 1444 2021.10
Language：English Publishing type：Research paper (scientific journal) Publisher：European Journal of Preventive Cardiology
Background: Air pollution including particulate matter with an aerodynamic diameter ≤2.5 µm (PM ) increases the risk of acute myocardial infarction. However, whether short-term exposure to PM triggers the onset of myocardial infarction with nonobstructive coronary arteries, compared with myocardial infarction with coronary artery disease, has not been elucidated. This study aimed to estimate the association between short-term exposure to PM and admission for acute myocardial infarction, myocardial infarction with coronary artery disease, and myocardial infarction with nonobstructive coronary arteries. Design: This was a time-stratified case-crossover study and multicenter validation study. Methods: This study used a nationwide administrative database in Japan between April 2012–March 2016. Of 137,678 acute myocardial infarction cases, 123,633 myocardial infarction with coronary artery disease and 14,045 myocardial infarction with nonobstructive coronary arteries were identified by a validated algorithm combined with International Classification of Disease (10th revision), diagnostic, and procedure codes. Air pollutants and meteorological data were obtained from the monitoring station nearest to the admitting hospital. Results: In spring (March–May), the short-term increase of 10 µg/m in PM 2 days before admission was significantly associated with admission for acute myocardial infarction, myocardial infarction with nonobstructive coronary arteries, and myocardial infarction with coronary artery disease after adjustment for meteorological variables (odds ratio 1.060, 95% confidence interval 1.038–1.082; odds ratio 1.151, 1.079–1.227; odds ratio 1.049, 1.026–1.073, respectively), while the association was not significant in other variables. These associations were also observed after adjustment for other co-pollutants. The risk for myocardial infarction with nonobstructive coronary arteries (vs myocardial infarction with coronary artery disease) was associated with an even lower concentration of PM under the current environmental standards. Conclusions: This study showed the seasonal difference of acute myocardial infarction risk attributable to PM and the difference in the threshold of triggering the onset of acute myocardial infarction subtype. 2.5 2.5 2.5 2.5 2.5 2.5 3
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Antithrombotic Therapy for Atrial Fibrillation and Coronary Artery Disease in Patients With Prior Atherothrombotic Disease: A Post Hoc Analysis of the AFIRE Trial. Reviewed
Matsuzawa Y, Kimura K, Yasuda S, Kaikita K, Akao M, Ako J, Matoba T, Nakamura M, Miyauchi K, Hagiwara N, Hirayama A, Matsui K, Ogawa H, AFIRE Investigators.
Journal of the American Heart Association e020907 2021.10
Language：English Publishing type：Research paper (scientific journal)
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Hanatani S., Izumiya Y., Yamamoto M., Araki S., Fujisue K., Arima Y., Takashio S., Yamamoto E., Kaikita K., Matsushita K., Tsujita K.
International Journal of Obesity 45 ( 10 ) 2214 - 2220 2021.10
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Obesity
Background: Although sarcopenic obesity is associated with a higher risk of cardiovascular events compared with obesity without sarcopenia, it is difficult to diagnose sarcopenia in daily clinical settings. Recently, a simple scoring system has been developed to identify sarcopenia patients based on three variables (age, hand grip strength, and calf circumference). However, the utility of this score for cardiovascular risk stratification in patients with abdominal obesity is unknown. Methods: We calculated the sarcopenia score in 262 patients with abdominal obesity, defined as a waist circumference ≥90 cm in women or ≥85 cm in men. The composite endpoint of this study was cardiovascular mortality, nonfatal myocardial infarction, stroke, unstable angina, and heart failure hospitalization. Results: Of the 262 patients, 108 had a high sarcopenia score based on previously established criteria (≥105 in men and ≥120 in women). The patients with a high sarcopenia score had a significantly higher plasma level of B-type natriuretic peptide compared with those with a low sarcopenia score (median 56.7, interquartile range [28.2–142.9] vs. 37.9 [13.8–76.1] pg/mL; p < 0.0001). Kaplan–Meier curves revealed a significantly lower event-free survival rate in those with a high compared with a low sarcopenia score (log-rank test p = 0.001), even after adjustment for confounding factors using propensity score matching (log-rank test p = 0.009). Multivariate Cox proportional hazard analysis identified a high sarcopenia score (hazard ratio: 2.46; 95% confidence interval: 1.31–4.64, p = 0.005) as an independent predictor of the primary endpoints. The combination of a high sarcopenia score and low body mass index (<25 kg/m2) predicted a significantly higher risk of future adverse events (p = 0.005). Furthermore, patients with a high sarcopenia score and high B-type natriuretic peptide level (≥200 pg/mL) had the poorest prognosis (p < 0.0001). Conclusions: This simple screening test for sarcopenia can predict future adverse cardiovascular events in patients with abdominal obesity.
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Takae M., Fujisue K., Yamamoto E., Egashira K., Komorita T., Oike F., Nishihara T., Yamamoto M., Hirakawa K., Tabata N., Tokitsu T., Yamanaga K., Sueta D., Hanatani S., Nakamura T., Usuku H., Araki S., Arima Y., Takashio S., Suzuki S., Kaikita K., Matsushita K., Tsujita K.
ESC Heart Failure 8 ( 5 ) 3809 - 3821 2021.10
Language：English Publishing type：Research paper (scientific journal) Publisher：ESC Heart Failure
Background: Heart failure (HF)-related congestive hepatopathy is a well-recognized problem in management of HF. The fibrosis-4 (FIB4) index calculated by [age × aspartate aminotransferase (IU/L)/platelet count (109/L) × square root of alanine aminotransferase (IU/L)] is useful for evaluating liver stiffness. We aimed to investigate the impact of the FIB4 index on prognosis in patients with HF. Methods and results: Consecutive HF patients referred for hospitalization at Kumamoto University Hospital, Japan, were registered between 2006 and 2015. We observed cardiovascular outcomes in each type of HF [HF with reduced left ventricular ejection fraction (LVEF) (HFrEF), HF with mid-range LVEF (HFmrEF) and with preserved LVEF (HFpEF)] according to their FIB4 index; Group 1 (FIB4 index <1.3), Group 2 (FIB4 index: 1.3–2.67), and Group 3 (FIB4 index >2.67). This study enrolled 83 HFrEF patients, 117 HFmrEF patients, and 504 HFpEF patients. In HFpEF patients, the Kaplan–Meier curve revealed that Group 3 had a significantly higher rate of total cardiovascular events compared with the other two groups. By contrast, the occurrences of total cardiovascular events were not different among three groups in HFrEF and HFmrEF patients. Multivariate Cox proportional hazard analysis with significant factors in univariate analysis identified that the FIB4 index as an independent and significant predictor for future total cardiovascular events in HFpEF patients (hazard ratio: 1.09, 95% confidence interval: 1.03–1.15, P = 0.001). Conclusions: The FIB4 index was a significant predictor for total cardiovascular events in HFpEF.
DOI： 10.1002/ehf2.13351
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Bleeding and Subsequent Cardiovascular Events and Death in Atrial Fibrillation With Stable Coronary Artery Disease: Insights From the AFIRE Trial. Reviewed
Kaikita K, Yasuda S, Akao M, Ako J, Matoba T, Nakamura M, Miyauchi K, Hagiwara N, Kimura K, Hirayama A, Matsui K, Ogawa H, AFIRE Investigators.
Circulation. Cardiovascular interventions 14 ( 11 ) CIRCINTERVENTIONS120010476 2021.9
Authorship：Lead author, Corresponding author Language：English Publishing type：Research paper (scientific journal)
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Atarashi H., Uchiyama S., Inoue H., Kitazono T., Yamashita T., Shimizu W., Ikeda T., Kamouchi M., Kaikita K., Fukuda K., Origasa H., Shimokawa H.
Heart and Vessels 36 ( 9 ) 1410 - 1420 2021.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Heart and Vessels
The EXPAND Study demonstrated the effectiveness and safety of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) in routine clinical practice in Japan. This sub-analysis was conducted to reveal the effectiveness and safety of rivaroxaban in Japanese NVAF patients according to baseline creatinine clearance (CrCl) levels and rivaroxaban doses in the EXPAND Study. We examined 6806 patients whose baseline CrCl data were available and classified them into 2 groups: normal renal function group with CrCl ≥ 50 mL/min (n = 5326, 78%) and renal dysfunction group with CrCl < 50 mL/min (n = 1480, 22%). In the normal renal function group, 1609 (30%) received 10 mg/day (under-dose), while in the renal dysfunction group, 108 (7%) received 15 mg/day (over-dose). In the normal renal function group, under-dose of rivaroxaban was associated with higher all-cause mortality, while in the renal dysfunction group, over-dose was associated with higher incidence of major bleeding. In contrast, the incidence of stroke or systemic embolism was not different between the 2 groups regardless of the dose of rivaroxaban. In the propensity score matched analysis to adjust the difference in characteristics according to doses of rivaroxaban, the incidences of clinical outcomes were comparable between the 2 dose groups in both renal function groups. These results indicate that the dose of rivaroxaban should be reduced depending on the renal function, considering the balance between risks of bleeding and ischemia.
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Kanazawa H., Kaikita K., Ito M., Kawahara Y., Hoshiyama T., Kanemaru Y., Kiyama T., Iwashita S., Tabata N., Yamanaga K., Fujisue K., Sueta D., Takashio S., Arima Y., Araki S., Usuku H., Nakamura T., Izumiya Y., Sakamoto K., Suzuki S., Yamamoto E., Soejima H., Matsushita K., Tsujita K.
Journal of the American Heart Association 10 ( 17 ) e021551 2021.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of the American Heart Association
BACKGROUND: The clinical implication of vascular endothelial dysfunction in patients with atrial fibrillation (AF) remains un-clear. This study aimed to elucidate the correlation between changes in vascular endothelial function assessed by reactive hyperemia-peripheral arterial tonometry and the effect of sinus rhythm restoration after catheter ablation (CA) for AF. METHODS AND RESULTS: Consecutive 214 patients who underwent CA for AF were included in this single center, retrospective study. The natural logarithmic transformed reactive hyperemia-peripheral arterial tonometry index (LnRHI) of all patients was measured before CA as well as 3 and 6 months after CA. LnRHI in sinus rhythm was significantly higher than that in AF before CA. Multivariate logistic regression analysis revealed that the presence of AF was an independent risk factor for lowering of LnRHI (odds ratio, 4.092; P=0.002) before CA. The LnRHI was significantly improved 3 and 6 months after CA in patients without AF recurrence. Multivariate Cox hazard analysis revealed that changes in LnRHI from before to 3 months after CA independently correlated with recurrence of AF (hazard ratio, 0.106; P=0.001). Receiver operating characteristic analysis showed the decrease in LnRHI levels from before to 3 months after CA as a significant marker that suspects AF recurrence (area under the curve, 0.792; log-rank test, P<0.001). CONCLUSIONS: The presence of AF was independently correlated with the impaired vascular endothelial function assessed by the reactive hyperemia-peripheral arterial tonometry. Long-term sinus rhythm restoration after CA for AF might contribute to the improvement of vascular endothelial function, which may reflect the nonrecurrence of AF.
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Validation of the Khorana Venous Thromboembolism Risk Score in Japanese Cancer Patients. Reviewed
Akasaka-Kihara F, Sueta D, Ishii M, Maki Y, Hirakawa K, Tabata N, Ito M, Yamanaga K, Fujisue K, Hoshiyama T, Hanatani S, Kanazawa H, Takashio S, Arima Y, Araki S, Usuku H, Nakamura T, Suzuki S, Yamamoto E, Soejima H, Kaikita K, Matsushita K, Matsuoka M, Usuku K, Tsujita K
JACC. Asia 1 ( 2 ) 259 - 270 2021.9
Language：English Publishing type：Research paper (scientific journal)
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HE4 predicts progressive fibrosis and cardiovascular events in patients with dilated cardiomyopathy Reviewed
Yamamoto M., Hanatani S., Araki S., Izumiya Y., Yamada T., Nakanishi N., Ishida T., Yamamura S., Kimura Y., Arima Y., Nakamura T., Takashio S., Yamamoto E., Sakamoto K., Kaikita K., Matsushita K., Morimoto S., Ito T., Tsujita K.
Journal of the American Heart Association 10 ( 15 ) e021069 2021.8
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of the American Heart Association
BACKGROUND: Cardiac fibrosis plays a crucial role in the pathogenesis of dilated cardiomyopathy (DCM). HE4 (human epididymis protein 4) is a secretory protein expressed in activated fibroblasts that exacerbates tissue fibrosis. In the present study, we investigated the clinical utility of HE4 measurement in patients with DCM and its pathophysiological role in preclinical experi-ments in vivo and in vitro. METHODS AND RESULTS: We measured serum HE4 levels of 87 patients with DCM. Endomyocardial biopsy expressed severe fibrosis only in the high HE4 group (P<0.0001). Echocardiography showed that left ventricular end-diastolic diameter tends to decrease over time (58±7.3 to 51±6.6 mm; P<0.0001) in the low HE4 group (<59.65 pmol/L [median value]). HE4 was significantly associated with risk reduction of mortality and cardiovascular hospitalization in multivariate Cox model. In vivo, HE4 was highly expressed in kidney and lung tissue of mouse, and scarcely expressed in heart. In genetically induced DCM mouse model, HE4 expression increased in kidney but not in heart and lung. In vitro, supernatant from HE4-transfected human em-bryonic kidney 293T cells enhanced transdifferentiation of rat neonatal fibroblasts and increased expression of fibrosis-related genes, and this was accompanied by the activation of extracellular signal-regulated kinase signaling in cardiac fibroblasts. Treatment with an inhibitor of upstream signal of extracellular signal-regulated kinase or a neutralizing HE4 antibody canceled the profibrotic properties of HE4. CONCLUSIONS: HE4 functions as a secretory factor, activating cardiac fibroblasts, thereby inducing cardiac interstitial fibrosis. HE4 could be a promising biomarker for assessing ongoing fibrosis and a novel therapeutic target in DCM. REGISTRATION: URL: https://upload.umin.ac.jp/cgi-open-bin/ctr; Unique identifier: UMIN000043062.