Papers - KAIKITA Koichi
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Ikeda T., Atarashi H., Inoue H., Uchiyama S., Kitazono T., Yamashita T., Shimizu W., Kamouchi M., Kaikita K., Fukuda K., Origasa H., Sakuma I., Saku K., Okumura Y., Nakamura Y., Morimoto H., Matsumoto N., Tsuchida A., Ako J., Sugishita N., Shimizu S., Shimokawa H.
Tohoku Journal of Experimental Medicine 240 ( 4 ) 259 - 268 2016.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Tohoku Journal of Experimental Medicine
The use of rivaroxaban, a factor Xa inhibitor, has been increasing for prevention of ischemic stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) in Japan. We conducted the nationwide multicenter study, termed as the EXPAND Study, to address its effectiveness and safety in the real-world practice of patients with non-valvular AF in Japan. The EXPAND Study is a prospective, non-interventional, observational cohort study to evaluate the effectiveness and safety of rivaroxaban in non-valvular AF patients in a real-world clinical practice. A total of 7,178 patients with non-valvular AF were enrolled in 684 medical institutes between November 20, 2012 and June 30, 2014. As for the baseline demographic and clinical characteristics of 7,164 patients, the proportion of female patients was 32.2%, and those of patients with creatinine clearance < 50 mL/min and non-paroxysmal (persistent or permanent) AF were 21.8% and 55.1%, respectively. The proportions of patients complicated with hypertension, congestive heart failure, diabetes mellitus, and a history of ischemic stroke were 70.9%, 25.9%, 24.3%, and 20.2%, respectively. The proportions of patients with a CHADS score ≤ 1 and a CHA DS -VASc score ≤ 1 were 37.3% and 13.6%, respectively. They were followed up until March 31, 2016 for a mean follow-up period of approximately 2.5 years. The findings of the EXPAND Study will help to establish an appropriate treatment with rivaroxaban for Japanese patients with non-valvular AF. 2 2 2
DOI： 10.1620/tjem.240.259
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Association of CYP2C19 variants and epoxyeicosatrienoic acids on patients with microvascular angina Reviewed
Akasaka T., Sueta D., Arima Y., Tabata N., Takashio S., Izumiya Y., Yamamoto E., Yamamuro M., Tsujita K., Kojima S., Kaikita K., Kajiwara A., Morita K., Oniki K., Saruwatari J., Nakagawa K., Ogata Y., Matsui K., Hokimoto S.
American Journal of Physiology - Heart and Circulatory Physiology 311 ( 6 ) H1409 - H1415 2016.12
Language：English Publishing type：Research paper (scientific journal) Publisher：American Journal of Physiology - Heart and Circulatory Physiology
Categorization as a cytochrome P450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. Epoxyeicosatrienoic acids (EETs) are metabolites of arachi-donic acid by CYP2C19 epoxygenases and anti-inflammatory properties, especially in microvascular tissues. We examined the association of CYP2C19 polymorphisms and EETs on microvascular angina (MVA) caused by coronary microvascular dysfunction. We examined CYP2C19 genotypes in patients with MVA (« = 71) and healthy subjects as control (n = 71). MVA was defined as the absence of coronary artery stenosis and epicardial spasms and the presence of inversion of lactic acid levels between intracoronary and coronary sinuses in acetylcholine-provocation test or the adenosine-triphos-phate-induced coronary flow reserve ratio was below 2.5. CYP2C19 PM have two loss-of-functon alleles (*2, *3). We measured serum dihydroxyeicosatrienoic acid (DHET) as representative EET metabolite. MVA group showed significantly higher CYP2C19 PM incidence (35% vs. 16%; P = 0.007) and high sense C-reactive protein (hs-CRP) levels (0.127 ± 0.142 vs. 0.086 ± 0.097 mg/dl; P = 0.043) than those of controls. Moreover, in MVA group, hs-CRP levels in CYP2C19 PM were significantly higher than that of non-PM (0.180 ± 0.107 vs. 0.106 ± 0.149 mg/dl. P = 0.045). Multivariate analysis indicated that smoking, hypertension, high hs-CRP, and CYP2C19 PM are predictive factors for MVA. In MVA group, DHET levels for CYP2C19 PM were significantly lower than that of non-PM [10.9 ± 1.64 vs. 14.2 ± 5.39 ng/ml, P = 0.019 (11, 12-DHET); 15.2 ± 4.39 vs. 17.9 ± 4.73 ng/ml, P = 0.025 (14, 15-DHET)]. CYP2C19 variants are associated with MVA. The decline of EET-based defensive mechanisms owing to CYP2C19 variants may affect coronary microvascular dysfunction.
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Tsujita K., Kaikita K., Araki S., Yamada T., Nagamatsu S., Yamanaga K., Sakamoto K., Kojima S., Hokimoto S., Ogawa H.
BMC Cardiovascular Disorders 16 ( 1 ) 235 2016.11
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：BMC Cardiovascular Disorders
Background: Coronary plaques in patients with coronary vasospastic angina have been characterized by diffuse intima-media thickening with homogeneous fibrous tissue, without confluent necrotic tissue. However, coronary vasospasm can trigger coronary thrombosis, and may play an important role in the pathogenesis of acute coronary syndromes, though the precise morphological mechanisms underlying this process remain unclear. Case presentation: A 43-year-old man with a history of multivessel coronary vasospastic angina had been treated with long-acting diltiazem and fluvastatin since 2004. Eleven years later, following 1 month of medication nonadherence, he experienced recurrence of rest angina and myocardial infarction, with elevated high-sensitivity troponin T. An emergency coronary angiogram demonstrated no de novo lesions, and the current episode was diagnosed as intractable sustained coronary spasm-induced anterior myocardial infarction. Optical coherence tomography imaging revealed the coronary plaque with homogeneous high-intensity signal, and a clearly visualized intraplaque neovascular microchannel (NVMC) network. Conclusions: Neovascularization within a coronary atheroma is known to accelerate coronary atherosclerosis. The current case with coronary vasospastic angina highlights the role of NVMC formation in this process.
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A rare case of long-term survival with idiopathic dilatation of the pulmonary artery Reviewed
Sueta D., Sugamura K., Shimizu H., Shiota T., Yamamuro M., Hirakawa K., Sakamoto K., Tsujita K., Hanatani S., Yamamoto E., Araki S., Kanazawa H., Kojima S., Kaikita K., Hokimoto S., Komohara Y., Ogawa H.
International Journal of Cardiology 223 337 - 339 2016.11
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Cardiology
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Tokitsu T., Yamamoto E., Hirata Y., Kusaka H., Fujisue K., Sueta D., Sugamura K., Sakamoto K., Tsujita K., Kaikita K., Hokimoto S., Sugiyama S., Ogawa H.
European Journal of Heart Failure 18 ( 11 ) 1353 - 1361 2016.11
Language：English Publishing type：Research paper (scientific journal) Publisher：European Journal of Heart Failure
Aims: Although pulse pressure (PP) is a recognized risk factor for various cardiovascular diseases, its association with cardiovascular outcomes in patients with heart failure with preserved ejection fraction (HFpEF) is uncertain. Methods and results: We enrolled 512 of 951 consecutive HFpEF patients admitted to the Kumamoto University Hospital between 2007 and 2013 and divided them into five groups according to PP quintiles. Blood pressure and pulse wave velocity (PWV) were measured by an ankle–brachial index device. The PP values in HFpEF were significantly and positively correlated with PWV and LV stroke volume index, and were negatively correlated with estimated glomerular filtration rate and haemoglobin levels. Furthermore, plasma B-type natriuretic peptide levels in HFpEF patients with the lowest (<45 mmHg) and highest PP (≥75 mmHg) were significantly higher than those with other PP (45–74 mmHg). The percentage of total cardiovascular and heart failure (HF)-related events by PP category resulted in U- and J-shaped curves. The higher frequency of coronary-related events was nearly linear. In the Kaplan–Meier analysis, HFpEF patients with the lowest and highest PP quintiles had a significantly higher risk of cardiovascular and HF-related events than those with other PPs (45–74 mmHg) (log-rank test, both P < 0.01). Conversely, the frequency of coronary-related events in the highest PP group, but not in the lowest PP group, was significantly higher than in other PP groups. Conclusion: Pulse pressure lower than 45 mmHg and higher than 75 mmHg was closely associated with HFpEF prognosis, indicating the clinical significance of PP for risk stratification of HFpEF.
DOI： 10.1002/ejhf.559
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Hokimoto S., Tabata N., Yamanaga K., Sueta D., Akasaka T., Tsujita K., Sakamoto K., Yamamoto E., Yamamuro M., Izumiya Y., Kaikita K., Kojima S., Matsui K., Ogawa H.
International Journal of Cardiology 222 185 - 194 2016.11
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Cardiology
Background The aim was to examine the prevalence and characteristics of epicardial vasomotor abnormality (EVA) and coronary microvascular dysfunction (CMD) including endothelium-dependent (EDCMD) or -independent (EICMD) in patients following a second-generation drug-eluting stent (second DES) implantation without in-stent restenosis. Methods and results In 105 patients who underwent second DES implantation in the left anterior descending coronary artery (74 men; mean age, 67.9±9.6years), and in 105 suspected angina patients without stenting (65 men; mean age 66.4±9.1years), we evaluated EVA using the acetylcholine provocation test, EDCMD and EICMD by measuring the coronary flow reserve and the relationship between myocardial ischemia (intracoronary lactate production between aorta and coronary sinus and ST-T changes) or recurrent angina and vascular function. There was no difference in the incidence of EVA between DES and control (49.5% versus 55.2%; P = 0.41). Given that the prevalence of CMD was higher in DES than in control (59.0% versus 29.5%; P < 0.001), CMD may be associated with stent placement. Of the CMD patients, EDCMD alone, EICMD alone, and both CMDs were found in 40.3%, 22.6%, and 37.1%, respectively. Myocardial ischemia was detected in 42.4% of patients, and recurrent angina was more common in the presence of both EDCMD and EICMD in patients with EVA or CMD compared to patients with normal vascular function (EVA, 42.9% versus 7.7%, P = 0.015: CMD, 39.1% versus 7.7%, P = 0.007). Conclusions Myocardial ischemia and recurrent angina may be caused by the presence of both EDCMD and EICMD after a second DES implantation without ISR.
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Tabata N., Sueta D., Akasaka T., Arima Y., Sakamoto K., Yamamoto E., Izumiya Y., Yamamuro M., Tsujita K., Kojima S., Kaikita K., Morita K., Oniki K., Saruwatari J., Nakagawa K., Hokimoto S.
PLoS ONE 11 ( 11 ) e0166240 2016.11
Language：English Publishing type：Research paper (scientific journal) Publisher：PLoS ONE
Background Helicobacter pylori infection and interleukin-1 polymorphisms are associated with an increased risk of gastric cancer. We examined the prevalence of Helicobacter pylori seropositivity and interleukin-1 polymorphisms between ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndrome patients. Methods We recruited consecutive acute coronary syndrome patients, and 101 non-ST-segment elevation acute coronary syndrome patients and 103 ST-segment elevation myocardial infarction patients were enrolled. Interleukin-1 polymorphism analyses were performed for single nucleotide polymorphism in interleukin-1 beta-511 and the variable number of tandem repeats polymorphism in the interleukin-1 receptor antagonist by polymerase chain reaction. Immunoglobulin G antibodies against Helicobacter pylori and high sensitivity C-reactive protein were also measured. Results The rates of the simultaneous presence of interleukin-1 polymorphisms and Helicobacter pylori-seropositivity between non-ST-segment elevation acute coronary syndrome and STsegment elevation myocardial infarction groups were 25.7% and 42.7%, respectively (P = 0.012). Helicobacter pylori-seropositive subjects with interleukin-1 polymorphisms showed significantly higher levels of high sensitivity C-reactive protein (0.04-0.12 vs. 0.02-0.05; P<0.001). Multivariate logistic regression analysis revealed that the carriage of Helicobacter pylori-seropositivity and interleukin-1 polymorphisms was significantly associated with STsegment elevation myocardial infarction (odds ratio, 2.32; 95% confidence interval, 1.23-4.37; P = 0.009). The C-statistic of conventional risk factors was 0.68 (P<0.001) and that including Helicobacter pylori-seropositivity and interleukin-1 polymorphisms was 0.70 (P<0.001); continuous net reclassification improvement was 34% (P = 0.0094) and integrated discrimination improvement was 3.0% (P = 0.014). Conclusions The coincidence of Helicobacter pylori-seropositivity and interleukin-1 polymorphisms was significantly associated with higher levels of high sensitivity C-reactive protein and the increased risk of ST-segment elevation myocardial infarction.
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Tsujita K., Yamanaga K., Komura N., Sakamoto K., Miyazaki T., Oimatsu Y., Ishii M., Tabata N., Akasaka T., Sueta D., Yamamoto E., Yamamuro M., Izumiya Y., Kojima S., Nakamura S., Kaikita K., Hokimoto S., Ogawa H.
International Journal of Cardiology 220 112 - 115 2016.10
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Cardiology
Background Although acute coronary syndrome (ACS) mainly arises from plaque ruptures (PR), precise mechanisms underlying ACS without PR are unknown. We sought to examine clinical, angiographic and intravascular ultrasound (IVUS) characteristics of ACS without PR. Methods and results Culprit lesions of 161 ACS patients were categorized by the presence or absence of PR (PR group: n = 57, Non-PR group: n = 104). Lower abdominal circumference (86 ± 10 cm vs 90 ± 9 cm, p = 0.02), lower prevalence of myocardial infarction (53% vs 82%, p = 0.0002), and higher prevalence of definite vasospasm (15% vs 2%, p = 0.006) were found in Non-PR group. Morphologically, Non-PR group was associated with simpler Ambrose classification (36% vs 14%, p = 0.004), less hypoechoic plaque (45% vs 65%, p = 0.04) and lower incidence of IVUS-detected thrombus (21% vs 54%, p < 0.0001), compared with PR group. On quantitative IVUS, although minimum lumen area (MLA) was similar between the groups, vessel (14.2 ± 5.4 mm vs 17.5 ± 5.1 mm , p = 0.0002) and plaque (11.6 ± 5.0 mm vs 14.9 ± 4.9 mm , p < 0.0001) areas were significantly smaller at MLA site in Non-PR group than in PR group. On multivariate analysis, average plaque area was only an independent IVUS-predictor of non-rupture ACS (odds ratio: 0.85, p = 0.01). Conclusion Compared to ACS with PR, non-rupture ACS arise from more hyperechoic (allegedly “stable”) plaque with smaller vessel and plaque area, leading to lower incidence of thrombotic occlusion. Coronary vasospasm might be a possible pathogenic mechanism underlying non-rupture ACS. 2 2 2 2
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Ishii M., Kaikita K., Sato K., Yamanaga K., Miyazaki T., Akasaka T., Tabata N., Arima Y., Sueta D., Sakamoto K., Yamamoto E., Tsujita K., Yamamuro M., Kojima S., Soejima H., Hokimoto S., Matsui K., Ogawa H.
International Journal of Cardiology 220 328 - 332 2016.10
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Cardiology
Background Coronary spasm is one of the mechanisms of myocardial infarction with nonobstructive coronary arteries (MINOCA). The aim of this study was to investigate the effects of aspirin on future cardiovascular events in patients with coronary vasospastic angina (VSA) with non-significant atherosclerotic stenosis. Methods This was the retrospective analysis of the 640 VSA patients with non-significant atherosclerotic stenosis (≤ 50% stenosis) among 1,877 consecutive patients who underwent acetylcholine (ACh)-provocation testing between January 1991 and December 2010. The patients were divided into 2 groups treated with (n = 137) or without (n = 503) low-dose aspirin (81–100 mg/day). We evaluated major adverse cardiac events (MACE), defined as cardiac death, nonfatal myocardial infarction, and unstable angina. Results In the study population, 24 patients (3.8%) experienced MACE; there were 6 cases in VSA patients with aspirin and 6 in those without aspirin. Multivariate Cox hazards analysis for correlated factors of MACE indicated that use of statin (HR: 0.11; 95% CI: 0.02 to 0.84; P = 0.033), ST-segment elevation during attack (HR: 5.28; 95% CI: 2.19–12.7; P < 0.001), but not the use of aspirin as a significant predictor of MACE. After propensity score matching (n = 112, each), Kaplan–Meier survival analysis indicated almost identical rate of 5-year survival free from MACE in those with aspirin, compared to those without aspirin in the entire and matched cohort (P = 0.640 and P = 0.541, respectively). Conclusions Low-dose aspirin might not reduce future cardiovascular events in VSA patients with non-significant stenosis.
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Changes in the risk factors for coronary spasm Reviewed
Ishii M., Kaikita K., Sato K., Yamanaga K., Miyazaki T., Akasaka T., Tabata N., Arima Y., Sueta D., Sakamoto K., Yamamoto E., Tsujita K., Yamamuro M., Kojima S., Soejima H., Hokimoto S., Matsui K., Ogawa H.
IJC Heart and Vasculature 12 85 - 87 2016.9
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：IJC Heart and Vasculature
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Usuku H., Yamamoto E., Kurogi K., Izumiya Y., Tsujita K., Yamamuro M., Kojima S., Soejima H., Kaikita K., Yamamoto N., Hokimoto S., Noda K., Yamabe H., Oshima S., Ogawa H.
IJC Metabolic and Endocrine 12 52 - 54 2016.9
Language：English Publishing type：Research paper (scientific journal) Publisher：IJC Metabolic and Endocrine
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Tsujita K., Yamanaga K., Komura N., Sakamoto K., Sugiyama S., Sumida H., Shimomura H., Yamashita T., Oka H., Nakao K., Nakamura S., Ishihara M., Matsui K., Sakaino N., Nakamura N., Yamamoto N., Koide S., Matsumura T., Fujimoto K., Tsunoda R., Morikami Y., Matsuyama K., Oshima S., Kaikita K., Hokimoto S., Ogawa H.
European Journal of Preventive Cardiology 23 ( 14 ) 1524 - 1528 2016.9
Language：English Publishing type：Research paper (scientific journal) Publisher：European Journal of Preventive Cardiology
Background The IMPROVE-IT trial showed that the clinical benefit of statin/ezetimibe combination appeared to be pronounced in patients with prior statin therapy. We hypothesized that the antiatherosclerotic effect of atorvastatin/ezetimibe combination was pronounced in patients with statin pretreatment. Methods In the prospective, randomized, controlled, multicenter PRECISE-IVUS trial, 246 patients undergoing intravascular ultrasound-guided percutaneous coronary intervention were randomized to atorvastatin/ezetimibe combination or atorvastatin alone. The dosage of atorvastatin was uptitrated with a treatment goal of lowering low-density lipoprotein cholesterol to below 70 mg/dl in both groups. Serial volumetric intravascular ultrasound was performed at baseline and 9-12 month follow-up to quantify the coronary plaque response in 202 patients. We compared the intravascular ultrasound endpoints in all subjects, stratified by the presence or absence of statin pretreatment. Results The baseline low-density lipoprotein cholesterol level (100.7 ± 23.1 mg/dl vs. 116.4 ± 25.9 mg/dl, p < 0.001) and lathosterol (55 (38 to 87)) μg/100 mg total cholesterol vs. 97 (57 to 149) μg/100 mg total cholesterol, p < 0.001) was significantly lower, and campesterol/lathosterol ratio (3.9 (2.4 to 7.4) vs. 2.6 (1.5 to 4.1), p < 0.001) was significantly increased in patients with statin pretreatment. Contrary to the patients without statin pretreatment (-'1.3 (-'3.1 to -'0.1)% vs. -'0.9 (-'2.3 to 0.9)%, p = 0.12), the atorvastatin/ezetimibe combination showed a significantly stronger reduction in delta percent atheroma volume, compared with atorvastatin alone, in patients with statin pretreatment (-'1.8 (-'3.6 to -'0.3)% vs. -'0.1 (-'1.6 to 0.8)%, p = 0.002). Conclusion Compensatory increase in cholesterol absorption observed in statin-treated patients might attenuate the inhibitory effects of statins on coronary plaque progression. A low-dose statin/ezetimibe combination might be a promising option in statin-hyporesponder.
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Tsujita K., Yamanaga K., Komura N., Sakamoto K., Sugiyama S., Sumida H., Shimomura H., Yamashita T., Oka H., Nakao K., Nakamura S., Ishihara M., Matsui K., Sakaino N., Nakamura N., Yamamoto N., Koide S., Matsumura T., Fujimoto K., Tsunoda R., Morikami Y., Matsuyama K., Oshima S., Kaikita K., Hokimoto S., Ogawa H.
Atherosclerosis 251 367 - 372 2016.8
Language：English Publishing type：Research paper (scientific journal) Publisher：Atherosclerosis
Background and aims Although dual low-density lipoprotein cholesterol (LDL-C)-lowering therapy (DLLT) with statin-ezetimibe combination showed clinical benefit in patients with acute coronary syndrome (ACS) confirming “the lower, the better,” the underlying mechanisms of DLLT are still unknown. Methods PRECISE-IVUS trial evaluated the effects of DLLT on IVUS-derived coronary atherosclerosis and lipid profile, compared with atorvastatin monotherapy, quantifying the coronary plaque response in 100 ACS patients. We explored the potential predictors of plaque regression. Results Lower total cholesterol, LDL-C, triglyceride, remnant-like particles cholesterol, and stronger reduction of small dense LDL-C and cholesterol absorption markers were observed in patients with plaque regression compared to those with progression. Multivariate analysis revealed that achieved LDL-C was the strongest predictor for coronary plaque regression (95% CI: 0.944–1.000, p = 0.05), followed by age (95% CI: 0.994–1.096, p = 0.09). Conclusions Incremental LDL-C lowering by DLLT was associated with stronger coronary plaque regression, reconfirming that lowering LDL-C to levels below previous targets provided additional clinical benefit.
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Nagatsuka K., Miyata S., Kada A., Kawamura A., Nakagawara J., Furui E., Takiuchi S., Taomoto K., Kario K., Uchiyama S., Saito K., Nagao T., Kitagawa K., Hosomi N., Tanaka K., Kaikita K., Katayama Y., Abumiya T., Nakane H., Wada H., Hattori A., Kimura K., Isshiki T., Nishikawa M., Yamawaki T., Yonemoto N., Okada H., Ogawa H., Minematsu K., Miyata T.
Thrombosis and Haemostasis 116 ( 2 ) 356 - 368 2016.8
Language：English Publishing type：Research paper (scientific journal) Publisher：Thrombosis and Haemostasis
Several studies have indicated that approximately 25% of patients treated with aspirin exhibit high on-treatment platelet reactivity (HTPR), which is potentially associated with cardiovascular events (CVEs). However, this association is still controversial, since the mechanisms by which HTPR contributes to CVEs remain unclear and a no standardised definition of HTPR has been established. To determine whether HTPR is associated with CVE recurrence and what type of assay would best predict CVE recurrence, we conducted a multicentre prospective cohort study of 592 stable cardiovascular outpatients treated with aspirin monotherapy for secondary prevention. Their HTPR was determined by arachidonic acid- or collagen-induced aggregation assays using two different agonist concentrations. Residual cyclooxygenase (COX)-1 activity was assessed by measuring serum thromboxane (TX)B or urinary 11-dehydro TXB . Shear-induced platelet thrombus formation was also examined. We followed all patients for two years to evaluate how these seven indexes were related to the recurrence of CVEs (cerebral infarction, transient ischaemic attack, myocardial infarction, unstable angina, revascularisation, other arterial thrombosis, or cardiovascular death). Of 583 patients eligible for the analysis, CVEs occurred in 69 (11.8%>). A Cox regression model identified several classical risk factors associated with CVEs. However, neither HTPR nor high residual COX-1 activity was significantly associated with CVEs, even by applying cut-off values suggested in previous reports or a receiver-operating characteristic analysis. In conclusion, recurrence of CVEs occurred independently of HTPR and residual COX-1 activity. Thus, our findings do not support the use of platelet or COX-1 functional testing for predicting clinical outcomes in stable cardiovascular patients. 2 2
DOI： 10.1160/TH15-11-0864
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A simple sarcopenia screening test predicts future adverse events in patients with heart failure Reviewed
Onoue Y., Izumiya Y., Hanatani S., Tanaka T., Yamamura S., Kimura Y., Araki S., Sakamoto K., Tsujita K., Yamamoto E., Yamamuro M., Kojima S., Kaikita K., Hokimoto S.
International Journal of Cardiology 215 301 - 306 2016.7
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Cardiology
Background Progressive loss of skeletal muscle termed "sarcopenia" is an independent risk factor for mortality in patients with cardiovascular diseases. A simple screening test that can identify sarcopenia using three variables (age, grip strength and calf circumference) was recently developed. We evaluated the clinical utility of this screening test in patients with heart failure (HF). Methods and results HF patients were divided into the sarcopenia (n = 82) and non-sarcopenia (n = 37) groups based on the sarcopenia score. Circulating BNP and high-sensitive cardiac troponin T levels were significantly higher, and left ventricular ejection fraction was lower in the sarcopenia group than non-sarcopenia group. Kaplan-Meier curve showed that HF event-free survival rate was significantly lower in the sarcopenia group. Multivariate Cox proportional hazards analysis identified BNP (ln[BNP]) (hazard ratio [HR]: 1.58; 95% CI: 1.09-2.29, p = 0.02), hs-CRP (ln[CRP]) (HR: 1.82; 95% CI: 1.23-2.68; p < 0.01) and sarcopenia score (HR: 1.03; 95% CI: 1.01-1.05, p < 0.01) as independent predictors of HF events. In receiver operating characteristic analysis, adding the sarcopenia score to BNP levels increased an area under the curve for future HF events (sarcopenia score alone, 0.77; BNP alone, 0.82; combination, 0.89). Conclusions The sarcopenia screening test can be used to predict future adverse events in patients with HF.
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Tabata N., Hokimoto S., Akasaka T., Arima Y., Sakamoto K., Yamamoto E., Tsujita K., Izumiya Y., Yamamuro M., Kojima S., Kaikita K., Ogawa H.
Heart and Vessels 31 ( 7 ) 1038 - 1044 2016.7
Language：English Publishing type：Research paper (scientific journal) Publisher：Heart and Vessels
Chronic kidney disease (CKD) status might modify the predictive effect of peripheral endothelial dysfunction on cardiovascular events after percutaneous coronary intervention (PCI). The aim of this study was to examine the differential effect of peripheral endothelial dysfunction on clinical outcome after PCI between CKD and non-CKD patients. We conducted a cohort study of 435 patients following PCI. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m . Peripheral endothelial dysfunction was examined using reactive hyperemia-peripheral arterial tonometry index (RHI), and we divided patients into low- and high-natural logarithmic RHI (Ln-RHI) group. The endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, ischemic stroke, hospitalization due to unstable angina pectoris, and coronary revascularization. A total of 56 patients had a cardiovascular event. Patients who suffered a cardiovascular event had significantly lower Ln-RHI than other patients in the non-CKD group (0.46 ± 0.18 versus 0.60 ± 0.25; P = 0.002). Kaplan–Meier analysis demonstrated a significantly higher probability of cardiovascular events in low Ln-RHI patients in the non-CKD group (log-rank test: P = 0.003). Multivariate Cox proportional hazards analysis identified Ln-RHI as an independent and significant predictor of future cardiovascular events in the non-CKD group (HR: 0.096; 95 % CI 0.02–0.47; P = 0.004) but not in the CKD group. There was a differential effect of peripheral endothelial dysfunction on clinical outcome after PCI between CKD and non-CKD patients, and peripheral endothelial dysfunction significantly correlates with subsequent cardiovascular events after PCI in non-CKD patients. 2
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Sueta D., Kaikita K., Okamoto N., Yamabe S., Ishii M., Arima Y., Ito M., Oimatsu Y., Iwashita S., Takahashi A., Sakamoto K., Tsujita K., Nakamura E., Hokimoto S., Mizuta H., Ogawa H.
Clinical Trials and Regulatory Science in Cardiology 19 1 - 4 2016.7
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Clinical Trials and Regulatory Science in Cardiology
Background Deep vein thrombosis (DVT) after total knee arthroplasty (TKA) often results in a fatal pulmonary thromboembolism (PTE). Edoxaban is an activated factor X inhibitor, which has been shown to prevent thromboembolic events in venous thromboembolism (VTE). Recently, the Total-Thrombus-formation Analysis System (T-TAS™), a microchip-based flow chamber system capable of evaluating thrombogenicity, was developed. In this study, utilizing the T-TAS™, we will examine the incidence of VTE after TKA and evaluate how thromboses form. Methods/design This study will be a prospective, single-center, open-label, randomized, controlled clinical trial aimed at exploring the efficacy of edoxaban in reducing the incidence of VTE after TKA. A total of 80 patients who will undergo TKA will be randomly and evenly divided into groups receiving edoxaban plus physiotherapy or physiotherapy alone. The primary outcome measures will include the incidence rate of VTE as detected by ultrasonography 7 days after TKA and the changes in T-TAS™ parameters. The secondary outcome measures will include the changes in prothrombin time and activated partial thromboplastin time, incidence of major/minor bleeding events and adverse effects of edoxaban. Discussion This study will provide clinical evidence on the combined efficacy and safety of edoxaban and physiotherapy compared with that of physiotherapy alone. This is will be the first prospective trial designed to explore how thrombus formation after TKA can be predicted by the T-TAS™.
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Hokimoto S., Tabata N., Sueta D., Akasaka T., Tsujita K., Sakamoto K., Kaikita K., Kojima S., Ogawa H.
Journal of Cardiology 68 ( 1 ) 20 - 28 2016.7
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Cardiology
Background: It is unknown to what extent coronary spasm affects cardiovascular events after percutaneous coronary intervention (PCI) in clinical practice. The aim was to examine the prevalence of cardiovascular events related to coronary spasm following PCI according to stent type. Methods: We enrolled 933 consecutive patients treated with coronary stent implantation, including bare metal stents (BMS; n = 238), first-generation drug-eluting stents (1st DES; n = 185), and second-generation DES (2nd DES; n = 510). We compared stent-oriented endpoints (SOEs; stent thrombosis, target vessel myocardial infarction or unstable angina, target lesion revascularization, and cardiac death) and the differences in SOE related to coronary spasm across stent types. Among the SOEs, spasm-related cardiac event was defined based on JCS guideline. Results: The prevalence of SOE for each stent type was 16.8% (BMS), 16.8% (1st DES), and 7.8% (2nd DES) (p < 0.001) and the rates of cardiovascular events related to coronary spasm were 2.9%, 3.2%, and 0.4%, respectively (p = 0.005). Multivariate analysis identified the non-use of statin (HR, 0.275, 95% CI, 0.087-0.871, p = 0.028) and non-use of 2nd DES (hazard ratio, 0.196, 95% confidence interval, 0.043-0.887, p = 0.034) as independent predictors of cardiac events related to coronary spasm. Conclusion: The prevalence of cardiovascular events related to coronary spasm was the lowest in patients with 2nd DES. The 2nd DES may be more efficacious and safer from the point of view of the reduction of cardiac events due to coronary spasm during statin therapy.
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Tabata N., Hokimoto S., Akasaka T., Sueta D., Arima Y., Sakamoto K., Yamamoto E., Izumiya Y., Yamamuro M., Tsujita K., Kojima S., Kaikita K., Morita K., Oniki K., Saruwatari J., Nakagawa K., Ogawa H.
International Journal of Cardiology 212 54 - 56 2016.6
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Cardiology
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Komura N., Tsujita K., Yamanaga K., Sakamoto K., Kaikita K., Hokimoto S., Iwashita S., Miyazaki T., Akasaka T., Arima Y., Yamamoto E., Izumiya Y., Yamamuro M., Kojima S., Tayama S., Sugiyama S., Matsui K., Nakamura S., Hibi K., Kimura K., Umemura S., Ogawa H.
Journal of the American Heart Association 5 ( 6 ) 2016.6
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of the American Heart Association
Background--Drug-eluting stents are replacing bare-metal stents, but in-stent restenosis (ISR) remains a problem. Reactive hyperemia index (RHI) assessed by peripheral arterial tonometry evaluates endothelial function noninvasively. We prospectively assessed the prognostic value of RHI in predicting ISR after percutaneous coronary intervention. Methods and Results--RHI was measured before percutaneous coronary intervention and at follow-up (F/U) angiography (F/U RHI; 6 and 9 months post bare-metal stents- and drug-eluting stents- percutaneous coronary intervention, respectively) in 249 consecutive patients. At F/U, ISR (stenosis > 50% of diameter) was seen in 68 patients (27.3%). F/U natural logarithm (RHI) was significantly lower in patients with ISR than in those without (0.52±0.23 versus 0.65±0.27, P < 0.01); no between-group difference in initial natural logarithm (RHI) (0.60±0.26 versus 0.62±0.25, P=0.56) was seen. By multivariate logistic regression analysis, even after adjusting for other significant parameters in univariate analysis, F/U natural logarithm (RHI) independently predicted ISR (odds ratio: 0.13; 95% CI: 0.04-0.48; P=0.002). In receiver operating-characteristic analysis, F/U RHI was the strongest predictor of ISR (area under the curve: 0.67; 95% CI: 0.60-0.75; P < 0.01; RHI < 1.73 had 67.6% sensitivity, 64.1% specificity); area under the curve significantly improved from 0.62 to 0.70 when RHI was added to traditional ISR risk factors (P=0.02). Net reclassification index was significant after addition of RHI (26.5%, P=0.002). Conclusions--Impaired RHI at F/U angiography independently correlated with ISR, adding incremental prognostic value to the ISRrisk stratification following percutaneous coronary intervention.