@article{pmid38505484,

title = {Machine learning-based gait analysis to predict clinical frailty scale in elderly patients with heart failure},

author = {Yoshifumi Mizuguchi and Motoki Nakao and Toshiyuki Nagai and Yuki Takahashi and Takahiro Abe and Shigeo Kakinoki and Shogo Imagawa and Kenichi Matsutani and Takahiko Saito and Masashige Takahashi and Yoshiya Kato and Hirokazu Komoriyama and Hikaru Hagiwara and Kenji Hirata and Takahiro Ogawa and Takuto Shimizu and Manabu Otsu and Kunihiro Chiyo and Toshihisa Anzai},

doi = {10.1093/ehjdh/ztad082},

issn = {2634-3916},

year  = {2024},

date = {2024-03-01},

urldate = {2024-03-01},

journal = {Eur Heart J Digit Health},

volume = {5},

number = {2},

pages = {152--162},

abstract = {AIMS: Although frailty assessment is recommended for guiding treatment strategies and outcome prediction in elderly patients with heart failure (HF), most frailty scales are subjective, and the scores vary among raters. We sought to develop a machine learning-based automatic rating method/system/model of the clinical frailty scale (CFS) for patients with HF.nnMETHODS AND RESULTS: We prospectively examined 417 elderly (≥75 years) with symptomatic chronic HF patients from 7 centres between January 2019 and October 2023. The patients were divided into derivation ( = 194) and validation ( = 223) cohorts. We obtained body-tracking motion data using a deep learning-based pose estimation library, on a smartphone camera. Predicted CFS was calculated from 128 key features, including gait parameters, using the light gradient boosting machine (LightGBM) model. To evaluate the performance of this model, we calculated Cohen's weighted kappa (CWK) and intraclass correlation coefficient (ICC) between the predicted and actual CFSs. In the derivation and validation datasets, the LightGBM models showed excellent agreements between the actual and predicted CFSs [CWK 0.866, 95% confidence interval (CI) 0.807-0.911; ICC 0.866, 95% CI 0.827-0.898; CWK 0.812, 95% CI 0.752-0.868; ICC 0.813, 95% CI 0.761-0.854, respectively]. During a median follow-up period of 391 (inter-quartile range 273-617) days, the higher predicted CFS was independently associated with a higher risk of all-cause death (hazard ratio 1.60, 95% CI 1.02-2.50) after adjusting for significant prognostic covariates.nnCONCLUSION: Machine learning-based algorithms of automatically CFS rating are feasible, and the predicted CFS is associated with the risk of all-cause death in elderly patients with HF.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{NAKAO2024132014,

title = {Iron supplementation is a residual piece of management in Asian patients with heart failure?},

author = {Motoki Nakao and Toshiyuki Nagai and Toshihisa Anzai},

url = {https://www.sciencedirect.com/science/article/pii/S0167527324006077},

doi = {https://doi.org/10.1016/j.ijcard.2024.132014},

issn = {0167-5273},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {International Journal of Cardiology},

pages = {132014},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{KOBAYASHI2024,

title = {Multimodal Assessment of Immunosuppressive Therapy in a Patient with Chronic Active Myocarditis 3 months following COVID-19 Infection},

author = {Yuta Kobayashi and Takeshi Hamaya and Toshiyuki Nagai and Yuki Mori and Takuma Sato and Satonori Tsuneta and Kento Wakabayashi and Kohsuke Kudo and Yoshihiro Matsuno and Toshihisa Anzai},

url = {https://www.sciencedirect.com/science/article/pii/S2589790X24001422},

doi = {https://doi.org/10.1016/j.cjco.2024.03.010},

issn = {2589-790X},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {CJC Open},

abstract = {There is limited evidence available regarding the efficacy of immunosuppressive therapy for post Coronavirus disease 2019 (COVID-19) chronic active myocarditis. We present a case of a 28-year-old woman with post COVID-19 virus-negative chronic active myocarditis. Immunosuppressive therapy improved the left ventricular ejection fraction from 21% to 42%, and ameliorated inflammatory activity as assessed by cardiac magnetic resonance imaging (CMR) and endomyocardial biopsy (EMB). This is the first report to evaluate inflammatory activity before and after immunosuppressive therapy in post COVID-19 virus-negative chronic active myocarditis using both EMB and CMR.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37591415,

title = {Association of longitudinal cardiac troponin trajectory with adverse events in patients with cardiac sarcoidosis},

author = {Sho Kazui and Sakae Takenaka and Toshiyuki Nagai and Yoshiya Kato and Hirokazu Komoriyama and Yuta Kobayashi and Akinori Takahashi and Kiwamu Kamiya and Takuma Sato and Atsushi Tada and Yutaro Yasui and Michikazu Nakai and Takahiro Sato and Ichizo Tsujino and Satoshi Konno and Toshihisa Anzai},

doi = {10.1016/j.ijcard.2023.131268},

issn = {1874-1754},

year  = {2023},

date = {2023-10-01},

urldate = {2023-10-01},

journal = {Int J Cardiol},

volume = {389},

pages = {131268},

abstract = {BACKGROUND: Although high-sensitivity cardiac troponins may be sensitive and easily repeatable markers of disease activity in patients with cardiac sarcoidosis (CS), the association between longitudinal cardiac troponin trajectory and adverse events remains unclear. This study aimed to clarify whether longitudinal cardiac troponin levels were associated with adverse events in patients with CS.nnMETHODS: We examined 63 consecutive CS-initiated prednisolone (PSL) patients with available longitudinal high-sensitivity cardiac troponin T (cTnT) data between December 2013 and March 2023. The area under the cTnT trajectory, which reflected cumulative cTnT release, was calculated to assess the association between longitudinal cTnT levels and adverse events. Patients were divided into two groups according to the median area under the cTnT trajectory per month. The primary outcome was a composite of sustained ventricular tachycardia or fibrillation, worsening heart failure, and sudden cardiac death (SCD).nnRESULTS: In total, 463 cTnT measurements were collected over a median follow-up period of 30.4 (interquartile range [IQR] 15.6-34.2) months. The primary outcome was observed in 12 (19%) patients. A higher area under the cTnT trajectory was significantly associated with an increased incidence of the primary outcome (P = 0.027), while cTnT levels before and one month after initiation of PSL, and these changes were not related to adverse events (P = 0.179, 0.096, and 0.95, respectively).nnCONCLUSIONS: Longitudinal cTnT trajectory following PSL initiation was associated with adverse cardiac events in patients with CS, suggesting that longitudinal measurement of cTnT would be useful for the early identification of high-risk patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37880721b,

title = {Differences in blood flow dynamics between balloon- and self-expandable valves in patients with aortic stenosis undergoing transcatheter aortic valve replacement},

author = {Yuki Takahashi and Kiwamu Kamiya and Toshiyuki Nagai and Satonori Tsuneta and Noriko Oyama-Manabe and Takeshi Hamaya and Sho Kazui and Yutaro Yasui and Kohei Saiin and Seiichiro Naito and Yoshifumi Mizuguchi and Sakae Takenaka and Atsushi Tada and Suguru Ishizaka and Yuta Kobayashi and Kazunori Omote and Takuma Sato and Yasushige Shingu and Kohsuke Kudo and Satoru Wakasa and Toshihisa Anzai},

doi = {10.1186/s12968-023-00970-9},

issn = {1532-429X},

year  = {2023},

date = {2023-10-01},

urldate = {2023-10-01},

journal = {J Cardiovasc Magn Reson},

volume = {25},

number = {1},

pages = {60},

abstract = {BACKGROUND: The differences in pre- and early post-procedural blood flow dynamics between the two major types of bioprosthetic valves, the balloon-expandable valve (BEV) and self-expandable valve (SEV), in patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR), have not been investigated. We aimed to investigate the differences in blood flow dynamics between the BEV and SEV using four-dimensional flow cardiovascular magnetic resonance (4D flow CMR).nnMETHODS: We prospectively examined 98 consecutive patients with severe AS who underwent TAVR between May 2018 and November 2021 (58 BEV and 40 SEV) after excluding those without CMR because of a contraindication, inadequate imaging from the analyses, or patients' refusal. CMR was performed in all participants before (median interval, 22 [interquartile range (IQR) 4-39] days) and after (median interval, 6 [IQR 3-6] days) TAVR. We compared the changes in blood flow patterns, wall shear stress (WSS), and energy loss (EL) in the ascending aorta (AAo) between the BEV and SEV using 4D flow CMR.nnRESULTS: The absolute reductions in helical flow and flow eccentricity were significantly higher in the SEV group compared in the BEV group after TAVR (BEV: - 0.22 ± 0.86 vs. SEV: - 0.85 ± 0.80, P < 0.001 and BEV: - 0.11 ± 0.79 vs. SEV: - 0.50 ± 0.88, P = 0.037, respectively); there were no significant differences in vortical flow between the groups. The absolute reduction of average WSS was significantly higher in the SEV group compared to the BEV group after TAVR (BEV: - 0.6 [- 2.1 to 0.5] Pa vs. SEV: - 1.8 [- 3.5 to - 0.8] Pa, P = 0.006). The systolic EL in the AAo significantly decreased after TAVR in both the groups, while the absolute reduction was comparable between the groups.nnCONCLUSIONS: Helical flow, flow eccentricity, and average WSS in the AAo were significantly decreased after SEV implantation compared to BEV implantation, providing functional insights for valve selection in patients with AS undergoing TAVR. Our findings offer valuable insights into blood flow dynamics, aiding in the selection of valves for patients with AS undergoing TAVR. Further larger-scale studies are warranted to confirm the prognostic significance of hemodynamic changes in these patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37307781,

title = {Prognostic Value of Liver Fibrotic Markers in Patients With Heart Failure},

author = {Atsushi Tada and Toshiyuki Nagai and Yoshiya Kato and Noriko Oyama-Manabe and Satonori Tsuneta and Michikazu Nakai and Yutaro Yasui and Sho Kazui and Yuki Takahashi and Kohei Saiin and Seiichiro Naito and Sakae Takenaka and Yoshifumi Mizuguchi and Yuta Kobayashi and Suguru Ishizaka and Kazunori Omote and Takuma Sato and Takao Konishi and Kiwamu Kamiya and Kohsuke Kudo and Toshihisa Anzai},

doi = {10.1016/j.amjcard.2023.05.033},

issn = {1879-1913},

year  = {2023},

date = {2023-08-01},

urldate = {2023-08-01},

journal = {Am J Cardiol},

volume = {200},

pages = {115--123},

abstract = {Several liver fibrotic markers are associated with prognosis in patients with heart failure (HF). However, the optimal markers for outcome prediction remain unclear. This study aimed to simultaneously investigate the prognostic value of liver fibrotic markers and the associations between these markers and clinical parameters in patients with HF without organic liver disease. We prospectively examined 211 consecutive patients with chronic HF between April 2018 and August 2021, excluding those with organic liver disease, using liver magnetic resonance imaging and ultrasound. A total of 7 representative liver fibrotic markers were measured in all patients. The primary outcome of interest was the composite of all-cause death and hospitalization for worsening HF. During a median follow-up period of 747 (interquartile range 465 to 1,042) days, the primary outcome occurred in 45 patients. Patients with higher hyaluronic acid and type III procollagen N-terminal peptide (P-III-P) levels showed a significantly higher incidence of the primary outcome than those without (p <0.001 and p = 0.005, respectively). The multivariable Cox regression analysis revealed that hyaluronic acid and P-III-P levels were independently associated with the risk of adverse events (hazard ratio 1.84, 95% confidence interval 1.18 to 2.87 and hazard ratio 2.89, 95% confidence interval 1.32 to 6.34, respectively) even after adjustment for a mortality prediction model, whereas the other 5 markers were not associated with the primary outcome. In conclusion, among the representative liver fibrotic markers, hyaluronic acid and P-III-P might be the optimal markers for outcome prediction in patients with HF.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36635468,

title = {Fragmented QRS on 12-lead electrocardiogram predicts long-term prognosis in patients with cardiac sarcoidosis},

author = {Hikaru Hagiwara and Masaya Watanabe and Takahide Kadosaka and Takuya Koizumi and Yuta Kobayashi and Taro Koya and Motoki Nakao and Satonori Tsuneta and Yoshiya Kato and Hirokazu Komoriyama and Rui Kamada and Toshiyuki Nagai and Kohsuke Kudo and Toshihisa Anzai},

doi = {10.1007/s00380-022-02229-2},

issn = {1615-2573},

year  = {2023},

date = {2023-06-01},

urldate = {2023-06-01},

journal = {Heart Vessels},

volume = {38},

number = {6},

pages = {803--816},

abstract = {Fragmented QRS (fQRS) on a 12-lead electrocardiogram is a known marker of fatal arrhythmias or cardiac adverse events in ischemic and non-ischemic cardiomyopathy patients. Nonetheless, the association between fQRS and clinical outcomes in patients with cardiac sarcoidosis (CS) remains unclear. Herein, we investigated whether fQRS is associated with long-term clinical outcomes in CS patients. A total of 78 patients who received immunosuppressive therapy (IST) for clinically diagnosed CS were retrospectively examined. Patients were classified into two groups according to the presence (n = 19) or absence (n = 59) of fQRS on electrocardiogram before IST. The primary outcome was the composite event of all-cause death, ventricular tachyarrhythmias (VTs), and hospitalization for heart failure. Results of late gadolinium enhancement on cardiac magnetic resonance imaging were also analyzed. During a median follow-up period of 3.7 years (interquartile range: 1.6-6.2 years), the primary outcome occurred more frequently in patients with fQRS than in those without (47% vs. 13%, log-rank p = 0.002). Multivariable Cox regression analyses showed that fQRS was an independent determinant of the primary outcome. The incidence of VTs, within 12 months of IST initiation, was comparable between the two groups; however, late-onset VTs, defined as those occurring ≥ 12 months after IST initiation, occurred more frequently in the fQRS group (21% vs. 2%, log-rank p = 0.002). The scar zone and scar border zone were greater in patients with fQRS than in those without it. In conclusion, our analysis suggests that fQRS is an independent predictor of adverse events, particularly late-onset VTs, in patients with CS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36495060,

title = {Applicability of new proposed criteria for iron deficiency in Japanese patients with heart failure},

author = {Atsushi Tada and Toshiyuki Nagai and Taro Koya and Motoki Nakao and Suguru Ishizaka and Yoshifumi Mizuguchi and Hiroyuki Aoyagi and Shogo Imagawa and Yusuke Tokuda and Masashige Takahashi and Yoshiya Kato and Masaharu Machida and Kenichi Matsutani and Takahiko Saito and Toshihisa Anzai},

doi = {10.1002/ehf2.14265},

issn = {2055-5822},

year  = {2023},

date = {2023-04-01},

urldate = {2023-04-01},

journal = {ESC Heart Fail},

volume = {10},

number = {2},

pages = {985--994},

abstract = {AIMS: Iron deficiency (ID) is a common co-morbidity in patients with heart failure (HF). A recent study showed that ID defined by the current guideline criteria was not associated with worse clinical outcomes, and new ID criteria was proposed in patients with HF. However, the external applicability of the new proposed criteria is unclear. We sought to investigate the applicability of the proposed ID criteria in Japanese patients with HF.nnMETHODS AND RESULTS: We prospectively examined 763 patients with chronic HF from a Japanese multicentre registry. The proposed ID criteria were transferrin saturation (TSAT) < 20% and serum iron ≤13 mmol/L and the guideline ID criteria were serum ferritin <100 ng/mL or, when ferritin was 100-299 ng/mL, TSAT <20%. Among all patients (456 male, mean age 71 ± 13 years), 213 (28%) and 444 (58%) met the proposed and guideline ID criteria, respectively. During a median follow-up period of 436 days (interquartile range 297-565), the primary outcome of all-cause mortality occurred in 56 (7%) patients. There was no significant difference in the primary outcome between the patients with and without guideline ID criteria (P = 0.32), whereas patients with serum iron ≤10 μmol/L showed higher mortality (P = 0.002). In multivariable Cox regressions, the proposed ID criteria, but not guideline ID criteria, were independently associated with the risk of all-cause mortality (HR 2.01, 95% CI 1.16-3.51 and HR 1.32, 95% CI 0.76-2.28, respectively), even after adjustment for covariates.nnCONCLUSIONS: When defined by the proposed criteria and not the guideline criteria, ID was associated with higher mortality in patients with chronic HF, suggesting that the proposed ID criteria is applicable to the Japanese population.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36908170,

title = {JCS 2023 Guideline on the Diagnosis and Treatment of Myocarditis},

author = {Toshiyuki Nagai and Takayuki Inomata and Takashi Kohno and Takuma Sato and Atsushi Tada and Toru Kubo and Kazufumi Nakamura and Noriko Oyama-Manabe and Yoshihiko Ikeda and Takeo Fujino and Yasuhide Asaumi and Takahiro Okumura and Toshiyuki Yano and Kazuko Tajiri and Hiroyuki Matsuura and Yuichi Baba and Haruki Sunami and Shingo Tsujinaga and Yasutoshi Ota and Keiko Ohta-Ogo and Yusuke Ishikawa and Hideo Matama and Nobutaka Nagano and Kimi Sato and Kazushi Yasuda and Yasushi Sakata and Koichiro Kuwahara and Tohru Minamino and Minoru Ono and Toshihisa Anzai},

doi = {10.1253/circj.CJ-22-0696},

issn = {1347-4820},

year  = {2023},

date = {2023-04-01},

urldate = {2023-04-01},

journal = {Circ J},

volume = {87},

number = {5},

pages = {674--754},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36326882,

title = {Liver stiffness assessed by magnetic resonance elastography predicts clinical outcomes in patients with heart failure and without chronic liver disease},

author = {Atsushi Tada and Toshiyuki Nagai and Yoshiya Kato and Kazunori Omote and Noriko Oyama-Manabe and Satonori Tsuneta and Yusuke Kudo and Mutsumi Nishida and Michikazu Nakai and Yuki Takahashi and Kohei Saiin and Seiichiro Naito and Yuta Kobayashi and Sakae Takenaka and Yoshifumi Mizuguchi and Kiwamu Kamiya and Takao Konishi and Takuma Sato and Kohsuke Kudo and Toshihisa Anzai},

doi = {10.1007/s00330-022-09209-0},

issn = {1432-1084},

year  = {2023},

date = {2023-03-01},

urldate = {2023-03-01},

journal = {Eur Radiol},

volume = {33},

number = {3},

pages = {2062--2074},

abstract = {OBJECTIVES: Evaluation of liver stiffness (LS) by magnetic resonance elastography (MRE) is useful for estimating right atrial pressure (RAP) in patients with heart failure (HF). However, its prognostic implications are unclear. We sought to investigate whether LS measured by MRE (LS-MRE) could predict clinical outcomes in patients with HF.nnMETHODS: We prospectively examined 207 consecutive HF patients between April 2018 and May 2021 after excluding those with organic liver disease. All patients underwent 3.0-T MRE. The primary outcome of interest was the composite of all-cause death and hospitalisation for HF.nnRESULTS: During a median follow-up period of 720 (interquartile range [IQR] 434-1013) days, the primary outcome occurred in 44 patients (21%), including 15 (7%) all-cause deaths and 29 (14%) hospitalisations for HF. The patients were divided into two groups according to median LS-MRE of 2.54 (IQR 2.34-2.82) kPa. Patients with higher LS-MRE showed a higher incidence of the primary outcome compared to those with lower LS-MRE (p < 0.001). Multivariable Cox regression analyses revealed that LS-MRE value was independently associated with the risk of adverse events (hazard ratio 2.49, 95% confidence interval 1.46-4.24). In multivariable linear regression, RAP showed a stronger correlation with LS-MRE (β coefficient = 0.31, p < 0.001) compared to markers related to liver fibrosis.nnCONCLUSIONS: In patients without chronic liver disease and presenting with HF, elevated LS-MRE was independently associated with worse clinical outcomes. Elevated LS-MRE may be useful for risk stratification in patients with HF and without chronic liver disease.nnKEY POINTS: • Magnetic resonance elastography (MRE) is an emerging non-invasive imaging technique for evaluating liver stiffness (LS) which can estimate right atrial pressure. • Elevated LS-MRE, which mainly reflects liver congestion, was independently associated with worse clinical outcomes in patients with heart failure. • The assessment of LS-MRE would be useful for stratifying the risk of adverse events in heart failure patients without chronic liver disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36705992b,

title = {Impact of right ventricular reserve on exercise capacity and quality of life in patients with left ventricular assist device},

author = {Sakae Takenaka and Takuma Sato and Toshiyuki Nagai and Kazunori Omote and Yuta Kobayashi and Kiwamu Kamiya and Takao Konishi and Atsushi Tada and Yoshifumi Mizuguchi and Yuki Takahashi and Seiichiro Naito and Kohei Saiin and Suguru Ishizaka and Satoru Wakasa and Toshihisa Anzai},

doi = {10.1152/ajpheart.00626.2022},

issn = {1522-1539},

year  = {2023},

date = {2023-03-01},

urldate = {2023-03-01},

journal = {Am J Physiol Heart Circ Physiol},

volume = {324},

number = {3},

pages = {H355--H363},

abstract = {Although measuring right ventricular (RV) function during exercise is more informative than assessing it at rest, the relationship between RV reserve function, exercise capacity, and health-related quality of life (HRQoL) in patients with left ventricular assist devices (LVAD) remains unresolved. We aimed to investigate whether RV reserve assessed by the change in RV stroke work index (RVSWI) during exercise is correlated with exercise capacity and HRQoL in patients with LVAD. We prospectively assessed 24 consecutive patients with LVAD who underwent invasive right heart catheterization in the supine position. Exercise capacity and HRQoL were assessed using the 6-min walk distance (6 MWD) and peak oxygen consumption (V̇o) in cardiopulmonary exercise testing, and the EuroQol visual analog scale (EQ-VAS), respectively. The patients were divided into two groups according to the median ΔRVSWI (change from rest to peak exercise). Patients with lower ΔRVSWI had significantly lower changes in cardiac index and absolute value of RV dP/d than those with higher ΔRVSWI. The ΔRVSWI was positively correlated with 6 MWD ( = 0.59,  = 0.003) and peak V̇o ( = 0.56,  = 0.006). In addition, ΔRVSWI was positively correlated with the EQ-VAS ( = 0.44,  = 0.030). In contrast, there was no significant correlation between RVSWI at rest and 6 MWD ( = -0.34,  = 0.88), peak V̇o ( = 0.074,  = 0.74), or EQ-VAS ( = 0.127,  = 0.56). Our findings suggest that the assessment of RV reserve function is useful for risk stratification in patients with LVAD. The change in right ventricular stroke work index (RVSWI) during exercise, not RVSWI at rest, was associated with exercise capacity and HRQoL. Our findings suggest that the assessment of change in RVSWI during exercise as a surrogate of RV reserve function may aid in risk stratification of patients with LVAD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36122643,

title = {Determinants of exercise capacity in patients with heart failure without left ventricular hypertrophy},

author = {Suguru Ishizaka and Hiroyuki Iwano and Shingo Tsujinaga and Michito Murayama and Satonori Tsuneta and Hiroyuki Aoyagi and Yoji Tamaki and Ko Motoi and Yasuyuki Chiba and Asuka Tanemura and Masahiro Nakabachi and Shinobu Yokoyama and Hisao Nishino and Kazunori Okada and Brett A Meyers and Pavlos P Vlachos and Takuma Sato and Kiwamu Kamiya and Masaya Watanabe and Sanae Kaga and Toshiyuki Nagai and Noriko Oyama-Manabe and Toshihisa Anzai},

doi = {10.1016/j.jjcc.2022.09.004},

issn = {1876-4738},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {J Cardiol},

volume = {81},

number = {1},

pages = {33--41},

abstract = {BACKGROUND: Determinants of exercise intolerance in a phenotype of heart failure with preserved ejection fraction (HFpEF) with normal left ventricular (LV) structure have not been fully elucidated.nnMETHODS: Cardiopulmonary exercise testing and exercise-stress echocardiography were performed in 44 HFpEF patients without LV hypertrophy. Exercise capacity was determined by peak oxygen consumption (peak VO). Doppler-derived cardiac output (CO), transmitral E velocity, systolic (LV-s') and early diastolic mitral annular velocities (e'), systolic pulmonary artery (PA) pressure (SPAP), tricuspid annular plane systolic excursion (TAPSE), and peak systolic right ventricular (RV) free wall velocity (RV-s') were measured at rest and exercise. E/e' and TAPSE/SPAP were used as an LV filling pressure parameter and RV-PA coupling, respectively.nnRESULTS: During exercise, CO, LV-s', RV-s', e', and SPAP were significantly increased (p < 0.05 for all), whereas E/e' remained unchanged and TAPSE/SPAP was significantly reduced (p < 0.001). SPAP was higher and TAPSE/SPAP was lower at peak exercise in patients showing lower-half peak VO. In univariable analyses, LV-s' (R = 0.35, p = 0.022), SPAP (R = -0.40, p = 0.008), RV-s' (R = 0.47, p = 0.002), and TAPSE/SPAP (R = 0.42, p = 0.005) were significantly correlated with peak VO. In multivariable analyses, not only SPAP, but also TAPSE/SPAP independently determined peak VO even after the adjustment for clinically relevant parameters.nnCONCLUSIONS: In HFpEF patients without LV hypertrophy, altered RV-PA coupling by exercise could be associated with exercise intolerance, which might not be caused by elevated LV filling pressure.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{TAMAKI202362,

title = {Application of an echocardiographic scoring system of left ventricular filling pressure to diagnose acute heart failure in patients complaining dyspnea},

author = {Yoji Tamaki and Hiroyuki Iwano and Michito Murayama and Suguru Ishizaka and Ko Motoi and Hiroyuki Aoyagi and Kosuke Nakamura and Mana Goto and Yukino Suzuki and Shinobu Yokoyama and Hisao Nishino and Masahiro Nakabachi and Sanae Kaga and Kiwamu Kamiya and Toshiyuki Nagai and Toshihisa Anzai},

url = {https://www.sciencedirect.com/science/article/pii/S0914508723001004},

doi = {https://doi.org/10.1016/j.jjcc.2023.04.016},

issn = {0914-5087},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Journal of Cardiology},

volume = {82},

number = {1},

pages = {62-68},

abstract = {Background 

Dyspnea is a common symptom in acute heart failure (AHF) patients. Although an accurate and rapid diagnosis of AHF is essential to improve prognosis, estimation of left ventricular (LV) filling pressure (FP) remains challenging, especially for noncardiologists. We evaluated the usefulness of a recently-proposed parameter of LV FP, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score, to detect AHF in patients complaining of dyspnea. 

Methods 

Echocardiography and lung ultrasonography (LUS) were performed in 121 consecutive patients (68 ± 14 years old, 75 males) presenting with dyspnea. The VMT score was determined from the atrioventricular valve opening phase (tricuspid valve first: 0, simultaneous: 1, mitral valve first: 2) and inferior vena cava dilatation (absent: 0, present: 1), and VMT ≥2 was judged as positive. LUS was performed with the 8 zones method and judged as positive if 3 or more B-lines were observed in bilateral regions. The AHF diagnosis was performed by certified cardiologists according to recent guidelines. 

Results Of the 121 patients, 33 were diagnosed with AHF. The sensitivity and specificity for diagnosing AHF were 64 % and 84 % for LUS and 94 % and 88 % for VMT score. In logistic regression analysis, VMT score showed a significantly higher c-index than LUS (0.91 vs 0.74},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35337935,

title = {Long-term preservation of functional capacity and quality of life in advanced heart failure patients with bridge to transplant therapy: A report from Japanese nationwide multicenter registry},

author = {Takuma Sato and Yuta Kobayashi and Toshiyuki Nagai and Takeshi Nakatani and Jon Kobashigawa and Yoshikatsu Saiki and Minoru Ono and Satoru Wakasa and Toshihisa Anzai},

doi = {10.1016/j.ijcard.2022.03.044},

issn = {1874-1754},

year  = {2022},

date = {2022-06-01},

urldate = {2022-06-01},

journal = {Int J Cardiol},

volume = {356},

pages = {66--72},

abstract = {BACKGROUND: Under the revised heart allocation system in the United States, bridge to transplant (BTT) patients with left ventricular assist device (LVAD) have a longer waitlist period, as they are now lowly prioritized. However, little is known regarding the long-term trajectory of functional capacity (FC) and health-related quality of life (HR-QOL) among BTT-LVAD patients.nnMETHODS: We retrospectively analyzed 442 consecutive patients with BTT-LVAD between April 2013 and May 2019 from a Japanese nationwide registry. FC (New York Heart Association [NYHA] functional class, peak oxygen uptake [VO], and 6-min walk test [6MWT]) and HR-QOL (European Quality of Life [EQ-5D index] and Visual Analogue Scale [EQ-VAS]) were assessed at baseline and for up to 60 months after LVAD implantation.nnRESULTS: During the follow-up period of 30 months (IQR 18-42 months), 100 (22.6%) patients underwent transplantation, 37 (8.3%) died, and 14 (3.1%) underwent explantation for recovery. Mean peak VO, 6MWT distance, EQ-5D index, and EQ-VAS significantly improved 3 months after LVAD implantation (p = 0.0012, p = 0.0037, p < 0.001, p < 0.001, respectively). Furthermore, these improvements were sustained for up to 60 months following LVAD implantation. Major adverse events including device failure, infection, stroke, and bleeding, which occurred within the first 3 months after LVAD implantation may have not affected FC or HR-QOL for up to 60 months (p = 0.15, p = 0.22, respectively).nnCONCLUSIONS: BTT patients showed long-term preservation of FC and HR-QOL, suggesting that BTT remains an option despite the long waiting time to HTx.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34634448,

title = {Hospitalization for Heart Failure in the United States, UK, Taiwan, and Japan: An International Comparison of Administrative Health Records on 413,385 Individual Patients},

author = {Varun Sundaram and Toshiyuki Nagai and Chern-En Chiang and Yogesh N V Reddy and Tze-Fan Chao and Rosita Zakeri and Chloe Bloom and Michikazu Nakai and Kunihiro Nishimura and Chung-Lieh Hung and Yoshihiro Miyamoto and Satoshi Yasuda and Amitava Banerjee and Toshihisa Anzai and Daniel I Simon and Sanjay Rajagopalan and John G F Cleland and Jayakumar Sahadevan and Jennifer K Quint},

doi = {10.1016/j.cardfail.2021.08.024},

issn = {1532-8414},

year  = {2022},

date = {2022-03-01},

urldate = {2022-03-01},

journal = {J Card Fail},

volume = {28},

number = {3},

pages = {353--366},

abstract = {BACKGROUND: Registries show international variations in the characteristics and outcome of patients with heart failure (HF), but national samples are rarely large, and case selection may be biased owing to enrolment in academic centers. National administrative datasets provide large samples with a low risk of bias. In this study, we compared the characteristics, health care resource use (HRU) and outcomes of patients with primary HF hospitalizations (HFH) using electronic health records (EHR) from 4 high-income countries (United States, UK, Taiwan, Japan) on 3 continents.nnMETHODS AND RESULTS: We used electronic health record to identify unplanned HFH between 2012 and 2014. We identified 231,512, 10,991, 36,900, and 133,982 patients with a primary HFH from the United States, the UK, Taiwan, and Japan, respectively. HFH per 100,000 population was highest in the United States and lowest in Taiwan. Fewer patients in Taiwan and Japan were obese or had chronic kidney disease. The length of hospital stay was shortest in the United States (median 4 days) and longer in the UK, Taiwan, and Japan (medians of 7, 9, and 17 days, respectively). HRU during hospitalization was highest in Japan and lowest in UK. Crude and direct standardized in-hospital mortality was lowest in the United States (direct standardized rates 1.8, 95% confidence interval 1.7%-1.9%) and progressively higher in Taiwan (direct standardized rates 3.9, 95% CI 3.8%-4.1%), the UK (direct standardized rates 6.4, 95% CI 6.1%-6.7%), and Japan (direct standardized rates 6.7, 95% CI 6.6%-6.8%). The 30-day all-cause (25.8%) and HF (7.2%) readmissions were highest in the United States and lowest in Japan (11.9% and 5.1%, respectively).nnCONCLUSIONS: Marked international variations in patient characteristics, HRU, and clinical outcomes exist; understanding them might inform health care policy and international trial design.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33431716b,

title = {High-Density Lipoprotein Cholesterol and Cardiovascular Events in Patients with Stable Coronary Artery Disease Treated with Statins: An Observation from the REAL-CAD Study},

author = {Kazunori Omote and Isao Yokota and Toshiyuki Nagai and Ichiro Sakuma and Yoshihisa Nakagawa and Kiwamu Kamiya and Hiroshi Iwata and Katsumi Miyauchi and Yukio Ozaki and Kiyoshi Hibi and Takafumi Hiro and Yoshihiro Fukumoto and Hiroyoshi Mori and Seiji Hokimoto and Yasuo Ohashi and Hiroshi Ohtsu and Hisao Ogawa and Hiroyuki Daida and Satoshi Iimuro and Hiroaki Shimokawa and Yasushi Saito and Takeshi Kimura and Masunori Matsuzaki and Ryozo Nagai and Toshihisa Anzai},

doi = {10.5551/jat.59881},

issn = {1880-3873},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {J Atheroscler Thromb},

volume = {29},

number = {1},

pages = {50--68},

abstract = {AIM: The association between high-density lipoprotein cholesterol (HDL-C) level after statin therapy and cardiovascular events in patients with stable coronary artery disease (CAD) remains unclear. Thus, in this study, we sought to determine how HDL-C level after statin therapy is associated with cardiovascular events in stable CAD patients.nnMETHODS: From the REAL-CAD study which had shown the favorable prognostic effect of high-dose pitavastatin in stable CAD patients with low-density lipoprotein cholesterol (LDL-C) ＜120 mg/dL, 9,221 patients with HDL-C data at baseline and 6 months, no occurrence of primary outcome at 6 months, and reported non-adherence for pitavastatin, were examined. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina requiring emergent admission after 6 months of randomization. Absolute difference and ratio of HDL-C levels were defined as (those at 6 months-at baseline) and (absolute difference/baseline)×100, respectively.nnRESULTS: During a median follow-up period of 4.0 (IQR 3.2-4.7) years, the primary outcome occurred in 417 (4.5%) patients. The adjusted risk of all HDL-C-related variables (baseline value, 6-month value, absolute, and relative changes) for the primary outcome was not significant (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.91-1.08, HR 1.03, 95% CI 0.94-1.12, HR 1.05, 95% CI 0.98-1.12, and HR 1.08, 95% CI 0.94-1.24, respectively). Furthermore, adjusted HRs of all HDL-C-related variables remained non-significant for the primary outcome regardless of on-treatment LDL-C level at 6 months.nnCONCLUSIONS: After statin therapy with modestly controlled LDL-C, HDL-C level has little prognostic value in patients with stable CAD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34514715,

title = {Association of high serum soluble interleukin 2 receptor levels with risk of adverse events in cardiac sarcoidosis},

author = {Yuta Kobayashi and Takuma Sato and Toshiyuki Nagai and Kenji Hirata and Satonori Tsuneta and Yoshiya Kato and Hirokazu Komoriyama and Kiwamu Kamiya and Takao Konishi and Kazunori Omote and Hiroshi Ohira and Kohsuke Kudo and Satoshi Konno and Toshihisa Anzai},

doi = {10.1002/ehf2.13614},

issn = {2055-5822},

year  = {2021},

date = {2021-12-01},

urldate = {2021-12-01},

journal = {ESC Heart Fail},

volume = {8},

number = {6},

pages = {5282--5292},

abstract = {AIMS: Although soluble interleukin 2 receptor (sIL-2R) is a potentially useful biomarker in the diagnosis and evaluation of disease severity in patients with sarcoidosis, its prognostic implication in patients with cardiac sarcoidosis (CS) is unclear. We sought to investigate whether sIL-2R was associated with clinical outcomes and to clarify the relationship between sIL-2R levels and disease activity in patients with CS.nnMETHODS AND RESULTS: We examined 83 consecutive patients with CS in our hospital who had available serum sIL-2R data between May 2003 and February 2020. The primary outcome was a composite of advanced atrioventricular block, ventricular tachycardia or ventricular fibrillation, heart failure hospitalization, and all-cause death. Inflammatory activity in the myocardium and lymph nodes was assessed by  F-fluorideoxyglucose positron emission tomography/computed tomography. During a median follow-up period of 2.96 (IQR 2.24-4.27) years, the primary outcome occurred in 24 patients (29%). Higher serum sIL-2R levels (>538 U/mL, the median) were significantly related to increased incidence of primary outcome (P = 0.037). Multivariable Cox regression analysis showed that a higher sIL-2R was independently associated with an increased subsequent risk of adverse events (HR 3.71, 95% CI 1.63-8.44, P = 0.002), even after adjustment for significant covariates. sIL-2R levels were significantly correlated to inflammatory activity in lymph nodes (r = 0.346, P = 0.003) but not the myocardium (r = 0.131, P = 0.27).nnCONCLUSIONS: Increased sIL-2R is associated with worse long-term clinical outcomes accompanied by increased systemic inflammatory activity in CS patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34364907,

title = {Performance of the HFPEF and the HFA-PEFF scores for the diagnosis of heart failure with preserved ejection fraction in Japanese patients: A report from the Japanese multicenter registry},

author = {Atsushi Tada and Toshiyuki Nagai and Kazunori Omote and Hiroyuki Iwano and Shingo Tsujinaga and Kiwamu Kamiya and Takao Konishi and Takuma Sato and Hirokazu Komoriyama and Yuta Kobayashi and Sakae Takenaka and Yoshifumi Mizuguchi and Tomoya Sato and Kazuhiro Yamamoto and Tsutomu Yoshikawa and Yoshihiko Saito and Toshihisa Anzai},

doi = {10.1016/j.ijcard.2021.08.001},

issn = {1874-1754},

year  = {2021},

date = {2021-11-01},

urldate = {2021-11-01},

journal = {Int J Cardiol},

volume = {342},

pages = {43--48},

abstract = {BACKGROUND: Diagnosing heart failure with preserved ejection fraction (HFpEF) is challenging. Although the HFPEF score and HFA-PEFF algorithm have been proposed for diagnosing HFpEF, previous validation studies were conducted in stable chronic heart failure (HF). Moreover, information on their applicability in the Asian population is limited. We sought to investigate these scores' diagnostic performance for HFpEF in Japanese patients recently hospitalized due to acute decompensated HF.nnMETHODS: We examined patients with HFpEF recently hospitalized with acute decompensated HF from a nationwide HFpEF-specific multicenter registry (HFpEF group) and control patients who underwent echocardiography to investigate the cause of dyspnea in our hospital (Non-HFpEF group).nnRESULTS: The studied population included 372 patients (194 HFpEF group and 178 Non-HFpEF group; HFpEF prevalence, 52%). A high HFPEF score (6-9 points) could diagnose HFpEF with a high specificity of 97% and a positive predictive value (PPV) of 94%, and a low HFPEF score (0-1 point) could rule out HFpEF with a high sensitivity of 97% and a negative predictive value (NPV) of 93%. HFpEF could be diagnosed with a high HFA-PEFF score (5-6 points) (specificity, 84%; PPV, 82%) or ruled out with a low HFA-PEFF score (0-1 point) (sensitivity, 99%; NPV, 89%). The HFPEF score was significantly superior to the HFA-PEFF score in diagnostic accuracy (area under the curve: 0.89 vs. 0.82, respectively, p = 0.004).nnCONCLUSIONS: The HFPEF and the HFA-PEFF scores had acceptable diagnostic accuracy in diagnosing HFpEF in Japanese patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34217654,

title = {Applicability of the AHA/ACC/HRS Guideline for Implantable Cardioverter Defibrillator Implantation in Japanese Patients With Cardiac Sarcoidosis},

author = {Sakae Takenaka and Yuta Kobayashi and Toshiyuki Nagai and Yoshiya Kato and Hirokazu Komoriyama and Nobutaka Nagano and Kiwamu Kamiya and Takao Konishi and Takuma Sato and Kazunori Omote and Yoshifumi Mizuguchi and Atsushi Tada and Tomoya Sato and Hiroyuki Iwano and Kengo Kusano and Hatsue Ishibashi-Ueda and Toshihisa Anzai},

doi = {10.1016/j.jacep.2021.04.009},

issn = {2405-5018},

year  = {2021},

date = {2021-11-01},

urldate = {2021-11-01},

journal = {JACC Clin Electrophysiol},

volume = {7},

number = {11},

pages = {1410--1418},

abstract = {OBJECTIVES: This study aimed to assess, among Japanese patients with cardiac sarcoidosis (CS), the implantable cardioverter-defibrillator (ICD) recommendations from the 2017 American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death (SCD).nnBACKGROUND: Although ICDs are used to prevent SCD from ventricular tachycardia or ventricular fibrillation (VT/VF) in patients with CS, the generalizability of the AHA/ACC/HRS guidelines for Japanese patients with CS remains unclear.nnMETHODS: This study examined 188 consecutive patients with CS in 2 tertiary hospitals between 1979 and 2020. Patients were followed for a primary outcome of VT/VF or SCD.nnRESULTS: During a median follow-up of 5.68 years, the primary outcome occurred in 44 patients (23%). Patients with a Class I recommendation for ICD implantation showed the highest incidence of the primary outcome among patients in whom the guideline recommendations for ICD implantation were used (log-rank test; p = 0.03). However, compared with patients with left ventricular ejection fractions (LVEFs) ≤35%, there was no significant difference in the incidence of the primary outcome among patients with LVEFs >35% and those who required a permanent pacemaker (p = 0.31); similar results were observed in those with LVEFs >35% and late gadolinium enhancement during cardiovascular magnetic resonance imaging (p = 0.22).nnCONCLUSIONS: The American guideline recommendations for ICD implantation might be applicable to Japanese patients with CS. Implantation of an ICD may need to be considered in these patients if they require a permanent pacemaker or have late gadolinium enhancement, regardless of LVEF.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33383123,

title = {Presence and Relevance of Midsystolic Notching on Right Ventricular Outflow Tract Flow Velocity Envelopes in Pulmonary Hypertension due to Heart Failure},

author = {Yasuyuki Chiba and Hiroyuki Iwano and Michito Murayama and Sanae Kaga and Ko Motoi and Suguru Ishizaka and Shingo Tsujinaga and Asuka Tanemura and Shinobu Yokoyama and Masahiro Nakabachi and Hisao Nishino and Kazunori Okada and Kiwamu Kamiya and Toshiyuki Nagai and Toshihisa Anzai},

doi = {10.1016/j.echo.2020.12.018},

issn = {1097-6795},

year  = {2021},

date = {2021-06-01},

urldate = {2021-06-01},

journal = {J Am Soc Echocardiogr},

volume = {34},

number = {6},

pages = {690--692.e1},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34176516,

title = {Blood flow dynamics with four-dimensional flow cardiovascular magnetic resonance in patients with aortic stenosis before and after transcatheter aortic valve replacement},

author = {Hirokazu Komoriyama and Kiwamu Kamiya and Toshiyuki Nagai and Noriko Oyama-Manabe and Satonori Tsuneta and Yuta Kobayashi and Yoshiya Kato and Miwa Sarashina and Kazunori Omote and Takao Konishi and Takuma Sato and Shingo Tsujinaga and Hiroyuki Iwano and Yasushige Shingu and Satoru Wakasa and Toshihisa Anzai},

doi = {10.1186/s12968-021-00771-y},

issn = {1532-429X},

year  = {2021},

date = {2021-06-01},

urldate = {2021-06-01},

journal = {J Cardiovasc Magn Reson},

volume = {23},

number = {1},

pages = {81},

abstract = {BACKGROUND: Pre- and post-procedural hemodynamic changes which could affect adverse outcomes in aortic stenosis (AS) patients who undergo transcatheter aortic valve replacement (TAVR) have not been well investigated. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) enables accurate analysis of blood flow dynamics such as flow velocity, flow pattern, wall shear stress (WSS), and energy loss (EL). We sought to examine the changes in blood flow dynamics of patients with severe AS who underwent TAVR.nnMETHODS: We examined 32 consecutive severe AS patients who underwent TAVR between May 2018 and June 2019 (17 men, 82 ± 5 years, median left ventricular ejection fraction 61%, 6 self-expanding valve), after excluding those without CMR because of a contraindication or inadequate imaging from the analyses. We analyzed blood flow patterns, WSS and EL in the ascending aorta (AAo), and those changes before and after TAVR using 4D flow CMR.nnRESULTS: After TAVR, semi-quantified helical flow in the AAo was significantly decreased (1.4 ± 0.6 vs. 1.9 ± 0.8, P = 0.002), whereas vortical flow and eccentricity showed no significant changes. WSS along the ascending aortic circumference was significantly decreased in the left (P = 0.038) and left anterior (P = 0.033) wall at the basal level, right posterior (P = 0.011) and left (P = 0.010) wall at the middle level, and right (P = 0.012), left posterior (P = 0.019) and left anterior (P = 0.028) wall at the upper level. EL in the AAo was significantly decreased (15.6 [10.8-25.1 vs. 25.8 [18.6-36.2]] mW, P = 0.012). Furthermore, a significant negative correlation was observed between EL and effective orifice area index after TAVR (r = - 0.38, P = 0.034).nnCONCLUSIONS: In severe AS patients undergoing TAVR, 4D flow CMR demonstrates that TAVR improves blood flow dynamics, especially when a larger effective orifice area index is obtained.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32730825,

title = {Lower left ventricular ejection fraction and higher serum angiotensin-converting enzyme activity are associated with histopathological diagnosis by endomyocardial biopsy in patients with cardiac sarcoidosis},

author = {Hirokazu Komoriyama and Kazunori Omote and Toshiyuki Nagai and Yoshiya Kato and Nobutaka Nagano and Kazuhiro Koyanagawa and Kiwamu Kamiya and Takao Konishi and Takuma Sato and Yuta Kobayashi and Shingo Tsujinaga and Hiroyuki Iwano and Kengo Kusano and Satoshi Yasuda and Hisao Ogawa and Hatsue Ishibashi-Ueda and Toshihisa Anzai},

doi = {10.1016/j.ijcard.2020.07.034},

issn = {1874-1754},

year  = {2020},

date = {2020-12-01},

urldate = {2020-12-01},

journal = {Int J Cardiol},

volume = {321},

pages = {113--117},

abstract = {BACKGROUND: The histopathological diagnosis of cardiac sarcoidosis (CS) is challenging because of sampling error in endomyocardial biopsy (EMB) and the determinants of positive EMB are unclear. Reduced left ventricular ejection fraction (LVEF) is a simple parameter of the extent of myocardial damage, and higher serum angiotensin-converting enzyme (ACE) activity would indicate the spread of disease activity in CS patients. Thus, we sought to examine whether these parameters are related to the histopathological diagnosis of CS by EMB.nnMETHODS: A total of 94 consecutive clinically diagnosed CS patients between August 1986 and March 2019 who were admitted to two academic hospitals were examined. We determined EMB as positive if non-caseating epithelioid granulomas were confirmed in the myocardial tissue. Patients were divided into two groups according to positive (n = 37) and negative (n = 57) EMB. We assessed the relationship between LVEF, serum ACE activity and positive EMB.nnRESULTS: Multivariable analysis revealed that both LVEF and serum ACE were independently associated with positive EMB (OR 0.83, 95% CI 0.70-0.99; OR 1.39, 95% CI 1.02-1.90, respectively). Moreover, patients with both lower LVEF (<37%, median) and higher ACE activity (≥13.5 IU/L, median) had the highest frequency of positive EMB (p = .003). The combination of lower LVEF and higher serum ACE showed better specificity (91.2%) and positive predictive value (73.7%) than either LVEF or serum ACE alone for positive EMB.nnCONCLUSIONS: Lower LVEF and higher serum ACE activity were associated with positive EMB, suggesting that these parameters might be useful for predicting positive EMB in CS patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31990204,

title = {Elevated admission urinary -acetyl-β-D-glucosamidase level is associated with worse long-term clinical outcomes in patients with acute heart failure},

author = {Sayaka Funabashi and Kazunori Omote and Toshiyuki Nagai and Yasuyuki Honda and Hiroki Nakano and Satoshi Honda and Naotsugu Iwakami and Yasuhiro Hamatani and Michikazu Nakai and Kunihiro Nishimura and Yasuhide Asaumi and Takeshi Aiba and Teruo Noguchi and Kengo Kusano and Hiroyuki Yokoyama and Satoshi Yasuda and Hisao Ogawa and Toshihisa Anzai},

doi = {10.1177/2048872620901986},

issn = {2048-8734},

year  = {2020},

date = {2020-08-01},

urldate = {2020-08-01},

journal = {Eur Heart J Acute Cardiovasc Care},

volume = {9},

number = {5},

pages = {429--436},

abstract = {BACKGROUND: The prognostic significance of urinary -acetyl-β-D-glucosamidase in acute heart failure has not been fully elucidated. Accordingly, this study investigated whether urinary -acetyl-β-D-glucosamidase could be associated with subsequent adverse events in acute heart failure patients.nnMETHODS: We studied 708 consecutive acute heart failure patients who had accessible -acetyl-β-D-glucosamidase data on admission from the National Cerebral and Cardiovascular Center Acute Decompensated Heart Failure registry. We assessed the relationship between the admission -acetyl-β-D-glucosamidase level and the combined endpoint of all-cause death and worsening heart failure. Worsening heart failure was defined as worsening symptoms and signs of heart failure requiring intensification of intravenous therapy such as diuretics, vasodilators and inotropes or initiation of mechanical support after stabilisation with initial treatment during hospitalisation, or readmission due to heart failure after discharge.nnRESULTS: During a median follow-up period of 763 (interquartile range 431-1028) days, higher urinary -acetyl-β-D-glucosamidase was significantly related to increased events of all-cause death and worsening heart failure. In addition, patients with higher urinary -acetyl-β-D-glucosamidase and lower estimated glomerular filtration rate on admission had the worst clinical outcomes. In multivariable Cox regression, urinary -acetyl-β-D-glucosamidase on admission was independently associated with adverse events (hazard ratio 1.19, 95% confidence interval 1.04-1.35) even after adjustment by covariates including the baseline estimated glomerular filtration rate.nnCONCLUSIONS: Higher urinary -acetyl-β-D-glucosamidase level on admission was independently associated with worse clinical outcomes. Our findings indicate the potential value of assessing urinary -acetyl-β-D-glucosamidase on admission for further risk stratification in patients with acute heart failure.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31970993,

title = {Prognostic value of base excess as indicator of acid-base balance in acute heart failure},

author = {Hiroki Nakano and Toshiyuki Nagai and Yasuyuki Honda and Satoshi Honda and Naotsugu Iwakami and Chisa Matsumoto and Yasuhide Asaumi and Takeshi Aiba and Teruo Noguchi and Kengo Kusano and Hiroyuki Yokoyama and Hisao Ogawa and Satoshi Yasuda and Taishiro Chikamori and Toshihisa Anzai},

doi = {10.1177/2048872619898781},

issn = {2048-8734},

year  = {2020},

date = {2020-08-01},

urldate = {2020-08-01},

journal = {Eur Heart J Acute Cardiovasc Care},

volume = {9},

number = {5},

pages = {399--405},

abstract = {BACKGROUND: Acid-base balance can change as a result of pulmonary oedema and low tissue perfusion in acute heart failure patients. However, its long-term prognostic significance remains to be clarified.nnMETHODS: We prospectively examined a cohort of 472 consecutive acute heart failure patients who underwent arterial blood gas analysis on admission between January 2013 and May 2016. Acidaemia, alkalaemia and normal range of base excess were defined as pH <7.38, >7.42 and -2 to 2 mEq/L, respectively. The primary outcome was all-cause death.nnRESULTS: During a median follow-up period of 714 days, 101 patients died. Although there was no difference in mortality among patients with acidaemia, normal pH and alkalaemia ( = 0.92), patients with high base excess had the highest mortality compared with others. Multivariable Cox proportional hazard models revealed that high base excess was an independent determinant of mortality (hazard ratio 1.83, 95% confidence interval 1.08-3.13 (high versus normal base excess), hazard ratio 0.81, 95% confidence interval 0.47-1.41 (low versus normal base excess)), even after adjustment for significant prognostic covariates. Furthermore, regarding mortality stratified by base excess and carbon dioxide partial pressure (pCO), patients with high base excess (>2.1 mEq/L) and high pCO (>40 mmHg) had the highest mortality compared with others.nnCONCLUSIONS: High base excess, but not low base excess, on admission was associated with long-term mortality in acute heart failure patients, indicating the importance of evaluating acid-base balance on admission by base excess for stratifying the risk of mortality in patients with acute heart failure.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32347146,

title = {Procedural Volume and Outcomes After Percutaneous Coronary Intervention for Unprotected Left Main Coronary Artery DiseaseReport From the National Clinical Data (J-PCI Registry)},

author = {Tadao Aikawa and Kyohei Yamaji and Toshiyuki Nagai and Shun Kohsaka and Kiwamu Kamiya and Kazunori Omote and Taku Inohara and Yohei Numasawa and Kenichi Tsujita and Tetsuya Amano and Yuji Ikari and Toshihisa Anzai},

doi = {10.1161/JAHA.119.015404},

issn = {2047-9980},

year  = {2020},

date = {2020-05-01},

urldate = {2020-05-01},

journal = {J Am Heart Assoc},

volume = {9},

number = {9},

pages = {e015404},

abstract = {Background There is a limited evidence base to support the volume-outcome relationship in patients undergoing percutaneous coronary intervention (PCI) for unprotected left main coronary artery disease (UPLMD). This study aimed to evaluate the relationship between institutional and operator volume and in-hospital outcomes in patients undergoing PCI for unprotected left main coronary artery disease. Methods and Results We analyzed characteristics and clinical outcomes of 24 320 patients undergoing PCI for unprotected left main coronary artery disease at 1102 hospitals by 7244 operators using data from the Japanese nationwide J-PCI Registry (National PCI Data Registry) between January 2014 and December 2017. We classified institutions and operators into quartiles based on the mean annual volume of PCI. A generalized linear mixed-effects model was used to evaluate the association between institutional and operator PCI volume and in-hospital outcomes. Among the 24 320 patients, 4027 (16.6%), 6147 (25.3%), and 14 146 (58.2%) presented with ST-segment-elevation myocardial infarction, non-ST-segment-elevation acute coronary syndrome, and stable ischemic heart disease; their crude in-hospital mortality was 15%, 3.1%, and 0.3%, respectively. Compared with patients in the lowest quartile of institutional volume (1-216 PCIs/y), the adjusted odds ratio of in-hospital death in patients in the second (217-323 PCIs/y), third (324-487 PCIs/y), and fourth (488-3015 PCIs/y) quartile of institutional volume was 0.75 (95% CI, 0.51-1.10; =0.14), 0.87 (95% CI, 0.57-1.34; =0.54), and 0.51 (95% CI, 0.30-0.86; =0.01), respectively. These findings were consistent in rates of in-hospital death or any complication. Conversely, operator PCI volume was not significantly associated with in-hospital outcomes. Conclusions Institutional rather than operator-based PCI volume was associated with better in-hospital outcomes in patients undergoing PCI for unprotected left main coronary artery disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32004670,

title = {Optimal sampling in derivation studies was associated with improved discrimination in external validation for heart failure prognostic models},

author = {Naotsugu Iwakami and Toshiyuki Nagai and Toshiaki A Furukawa and Aran Tajika and Akira Onishi and Kunihiro Nishimura and Soshiro Ogata and Michikazu Nakai and Misa Takegami and Hiroki Nakano and Yohei Kawasaki and Ana Carolina Alba and Gordon Henry Guyatt and Yasuyuki Shiraishi and Shun Kohsaka and Takashi Kohno and Ayumi Goda and Atsushi Mizuno and Tsutomu Yoshikawa and Toshihisa Anzai},

doi = {10.1016/j.jclinepi.2020.01.011},

issn = {1878-5921},

year  = {2020},

date = {2020-05-01},

urldate = {2020-05-01},

journal = {J Clin Epidemiol},

volume = {121},

pages = {71--80},

abstract = {OBJECTIVES: The objective of the study was to identify determinants of external validity of prognostic models.nnSTUDY DESIGN AND SETTING: We systematically searched for studies reporting prognostic models of heart failure (HF) and examined their performance for predicting 30-day death in a cohort of consecutive 3,452 acute HF patients. We applied published critical appraisal tools and examined whether bias or other characteristics of original derivation studies determined model performance.nnRESULTS: We identified 224 models from 6,354 eligible studies. The mean c-statistic in the cohort was 0.64 (standard deviation, 0.07). In univariable analyses, only optimal sampling assessed by an adequate and valid description of the sampling frame and recruitment details to collect the population of interest (total score range: 0-2, higher scores indicating lower risk of bias) was associated with high performance (standardized β = 0.25, 95% CI: 0.12 to 0.38, P < 0.001). It was still significant after adjustment for relevant study characteristics, such as data source, scale of study, stage of illness, and study year (standardized β = 0.24, 95% CI: 0.07 to 0.40, P = 0.01).nnCONCLUSION: Optimal sampling representing the gap between the population of interest and the studied population in derivation studies was a key determinant of external validity of HF prognostic models.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31898963,

title = {Prognostic Value of Serum Uric Acid in Hospitalized Heart Failure Patients With Preserved Ejection Fraction (from the Japanese Nationwide Multicenter Registry)},

author = {Yuta Kobayashi and Kazunori Omote and Toshiyuki Nagai and Kiwamu Kamiya and Takao Konishi and Takuma Sato and Yoshiya Kato and Hirokazu Komoriyama and Shingo Tsujinaga and Hiroyuki Iwano and Kazuhiro Yamamoto and Tsutomu Yoshikawa and Yoshihiko Saito and Toshihisa Anzai},

doi = {10.1016/j.amjcard.2019.12.003},

issn = {1879-1913},

year  = {2020},

date = {2020-03-01},

urldate = {2020-03-01},

journal = {Am J Cardiol},

volume = {125},

number = {5},

pages = {772--776},

abstract = {Elevated serum uric acid (UA) is associated with an increased risk of cardiovascular disease and worse clinical outcome in patients with cardiovascular disease. Nevertheless, the prognostic value of serum UA level in hospitalized heart failure patients with preserved ejection fraction (HFpEF) has not been fully elucidated. The aim of this study was to investigate whether serum UA level on admission could be associated with subsequent mortality in hospitalized patients with HFpEF. We examined 516 consecutive hospitalized HFpEF (left ventricular ejection fraction ≥50%) patients with decompensated heart failure from our HFpEF-specific multicenter registry who had serum UA data on admission. The primary outcome of interest was all-cause death. During a median follow-up period of 749 (interquartile range 540 to 831) days, 90 (17%) patients died. Higher serum UA level was significantly related to increased incidence of all-cause death (p = 0.016). In addition, patients with higher serum UA (≥6.6 mg/dl, median) and plasma B-type natriuretic peptide (≥401.2 pg/ml, median) levels had the highest incidence of all-cause death in the groups (p = 0.002). In multivariable Cox regression analysis, serum UA was an independent determinant of mortality (hazards ratio 1.23, 95% confidence interval 1.10 to 1.39) even after adjustment for prespecified confounders, renal function and the use of diuretics before admission. In conclusions, higher admission serum UA was an independent determinant of mortality in hospitalized HFpEF patients. Our findings indicate the importance of assessing admission serum UA level for further risk stratification in hospitalized patients with HFpEF.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31851433,

title = {Left ventricular outflow tract velocity time integral in hospitalized heart failure with preserved ejection fraction},

author = {Kazunori Omote and Toshiyuki Nagai and Hiroyuki Iwano and Shingo Tsujinaga and Kiwamu Kamiya and Tadao Aikawa and Takao Konishi and Takuma Sato and Yoshiya Kato and Hirokazu Komoriyama and Yuta Kobayashi and Kazuhiro Yamamoto and Tsutomu Yoshikawa and Yoshihiko Saito and Toshihisa Anzai},

doi = {10.1002/ehf2.12541},

issn = {2055-5822},

year  = {2020},

date = {2020-02-01},

urldate = {2020-02-01},

journal = {ESC Heart Fail},

volume = {7},

number = {1},

pages = {167--175},

abstract = {AIMS: The prognostic implication of left ventricular outflow tract velocity time integral (LVOT-VTI) on admission in hospitalized heart failure with preserved ejection fraction (HFpEF) patients has not been determined. We sought to investigate whether LVOT-VTI on admission is associated with worse clinical outcomes in hospitalized patients with HFpEF.nnMETHODS AND RESULTS: We studied consecutive 214 hospitalized HFpEF patients who had accessible LVOT-VTI data on admission, from a prospective HFpEF-specific multicentre registry. The primary outcome of interest was the composite of all-cause death and readmission due to heart failure. During a median follow-up period of 688 (interquartile range 162-810) days, the primary outcome occurred in 83 patients (39%). The optimal cut-off value of LVOT-VTI for the primary outcome estimated by receiver operating characteristic analysis was 15.8 cm. Lower LVOT-VTI was significantly associated with the primary outcome compared with higher LVOT-VTI (P = 0.005). Multivariable Cox regression analyses revealed that lower LVOT-VTI was an independent determinant of the primary outcome (hazard ratio 0.94, 95% confidence interval 0.91-0.98). In multivariable linear regression, haemoglobin level was the strongest independent determinant of LVOT-VTI among clinical parameters (β coefficient = -0.61, P = 0.007). Furthermore, patients with lower LVOT-VTI and anaemia had the worst clinical outcomes among the groups (P < 0.001).nnCONCLUSIONS: Lower admission LVOT-VTI was an independent determinant of worse clinical outcomes in hospitalized HFpEF patients, indicating that LVOT-VTI on admission might be useful for categorizing a low-flow HFpEF phenotype and risk stratification in hospitalized HFpEF patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31344403,

title = {Long-term Prognostic Significance of Admission Tricuspid Regurgitation Pressure Gradient in Hospitalized Patients With Heart Failure With Preserved Ejection Fraction: A Report From the Japanese Real-World Multicenter Registry},

author = {Kazunori Omote and Toshiyuki Nagai and Kiwamu Kamiya and Tadao Aikawa and Shingo Tsujinaga and Yoshiya Kato and Hirokazu Komoriyama and Hiroyuki Iwano and Kazuhiro Yamamoto and Tsutomu Yoshikawa and Yoshihiko Saito and Toshihisa Anzai},

doi = {10.1016/j.cardfail.2019.07.010},

issn = {1532-8414},

year  = {2019},

date = {2019-12-01},

urldate = {2019-12-01},

journal = {J Card Fail},

volume = {25},

number = {12},

pages = {978--985},

abstract = {BACKGROUND: Doppler-estimated peak systolic tricuspid regurgitation pressure gradient (TRPG) is a representative noninvasive parameter for evaluating pulmonary artery systolic pressure, which can be a determinant of adverse outcomes in chronic heart failure with preserved ejection fraction (HFpEF). However, the prognostic implications of TRPG at admission for hospitalized patients with HFpEF are undetermined.nnMETHODS AND RESULTS: We examined 469 consecutive hospitalized patients with decompensated HFpEF (left ventricular ejection fraction ≥ 50%) who underwent TRPG measurement at admission in our HFpEF multicenter registry. The primary outcome of interest was all-cause death. Admission TRPG was significantly correlated with estimated pulmonary capillary wedge pressure and left atrial dimension (r = 0.24, P < 0.001 and r = 0.21, P < 0.001, respectively). During a median follow-up period of 748 (IQR 540-820) days, 83 patients died. Higher TRPG was significantly associated with higher mortality compared to lower TRPG (log-rank; P = 0.007). Multivariable analysis revealed that elevated TRPG was an independent determinant of mortality (HR 1.02, 95% CI 1.01-1.04, P = 0.008) after adjustment for prespecified confounders and renal function.nnCONCLUSIONS: Elevated TRPG at admission was an independent determinant of mortality in hospitalized patients with HFpEF, indicating that TRPG at admission could be a useful marker for risk stratification in these patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29846026,

title = {Validation of U.S. mortality prediction models for hospitalized heart failure in the United Kingdom and Japan},

author = {Toshiyuki Nagai and Varun Sundaram and Ahmad Shoaib and Yasuyuki Shiraishi and Shun Kohsaka and Kieran J Rothnie and Susan Piper and Theresa A McDonagh and Suzanna M C Hardman and Ayumi Goda and Atsushi Mizuno and Mitsuaki Sawano and Alan S Rigby and Jennifer K Quint and Tsutomu Yoshikawa and Andrew L Clark and Toshihisa Anzai and John G F Cleland},

doi = {10.1002/ejhf.1210},

issn = {1879-0844},

year  = {2018},

date = {2018-08-01},

urldate = {2018-08-01},

journal = {Eur J Heart Fail},

volume = {20},

number = {8},

pages = {1179--1190},

abstract = {AIMS: Prognostic models for hospitalized heart failure (HHF) were developed predominantly for patients of European origin in the United States of America; it is unclear whether they perform similarly in other health care systems or for different ethnicities. We sought to validate published prediction models for HHF in the United Kingdom (UK) and Japan.nnMETHODS AND RESULTS: Patients in the UK (n =894) and Japan (n =3158) were prospectively enrolled and were similar in terms of sex (∼60% men) and median age (∼77 years). Models predicted that British patients would have a higher mortality than Japanese, which was indeed true both for in-hospital (4.8% vs. 2.5%) and 180-day (20.7% vs. 9.5%) mortality. The model c-statistics for the published/derivation (range 0.70-0.76) and Japanese (range 0.75-0.77) cohorts were similar and higher than for the UK (0.62-0.75) but models consistently overestimated mortality in Japan. For in-hospital mortality, the OPTIMIZE-HF model performed best, providing similar discrimination in published/derivation, UK and Japanese cohorts [c-indices: 0.75 (0.74-0.77); 0.75 (0.68-0.81); and 0.77 (0.70-0.83), respectively], and least overestimated mortality in Japan. For 180-day mortality, the c-statistics for the ASCEND-HF model were similar in published/derivation (0.70) and UK [0.69 (0.64-0.74)] cohorts but higher in Japan [0.75 (0.71-0.79)]; calibration was good in the UK but again overestimated mortality in Japan.nnCONCLUSION: Calibration of published prediction models appears moderately accurate and unbiased when applied to British patients but consistently overestimates mortality in Japan. Identifying the reason why patients in Japan have a better than predicted prognosis is of great interest.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29880555,

title = {Elevated Plasma D-Dimer Level Is Associated With Short-Term Risk of Ischemic Stroke in Patients With Acute Heart Failure},

author = {Yasuhiro Hamatani and Toshiyuki Nagai and Michikazu Nakai and Kunihiro Nishimura and Yasuyuki Honda and Hiroki Nakano and Satoshi Honda and Naotsugu Iwakami and Yasuo Sugano and Yasuhide Asaumi and Takeshi Aiba and Teruo Noguchi and Kengo Kusano and Kazunori Toyoda and Satoshi Yasuda and Hiroyuki Yokoyama and Hisao Ogawa and Toshihisa Anzai},

doi = {10.1161/STROKEAHA.118.021899},

issn = {1524-4628},

year  = {2018},

date = {2018-07-01},

urldate = {2018-07-01},

journal = {Stroke},

volume = {49},

number = {7},

pages = {1737--1740},

abstract = {BACKGROUND AND PURPOSE: The incidence of heart failure increases the subsequent risk of ischemic stroke, and its risk could be higher in the short-term period after an acute heart failure (AHF) event. However, its determinants remain to be clarified. Plasma D-dimer level reflects fibrin turnover and exhibits unique properties as a biomarker of thrombosis. The aim of this study is to investigate whether D-dimer level is a determinant of short-term incidence of ischemic stroke in patients with AHF.nnMETHODS: We examined 721 consecutive hospitalized AHF patients with plasma D-dimer level on admission from our prospective registry between January 2013 and May 2016. The study end points were incidence of ischemic stroke during hospitalization and at 30 days after admission.nnRESULTS: Of the total participants (mean age, 76 years; male, 60%; atrial fibrillation, 54%; mean left ventricular ejection fraction, 38%), in-hospital ischemic stroke occurred in 18 patients (2.5%) during a median hospitalization period of 21 days, and 30-day ischemic stroke occurred in 16 patients (2.2%). Higher D-dimer level on admission was an independent determinant of subsequent risk of in-hospital ischemic stroke even after adjustment by CHADS-VASc score (odds ratio, 2.29; 95% confidence interval, 1.46-3.60; <0.001) or major confounders, including age, atrial fibrillation, and antithrombotic therapy (odds ratio, 2.31; 95% confidence interval, 1.43-3.74; <0.001). Subgroup analyses showed consistent findings in patients without atrial fibrillation (odds ratio, 2.46; 95% confidence interval, 1.39-4.54; =0.002) and those without antithrombotic therapy (odds ratio, 2.79; 95% confidence interval, 1.53-5.57; <0.001). Similar results were obtained for 30-day ischemic stroke as an alternative outcome.nnCONCLUSIONS: Elevated plasma D-dimer level on admission was significantly associated with increased incidence of ischemic stroke shortly after admission for AHF, suggesting a predictive role of D-dimer for short-term ischemic stroke events in patients with AHF.nnCLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000017024.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27856486,

title = {Myocardial Immunocompetent Cells and Macrophage Phenotypes as Histopathological Surrogates for Diagnosis of Cardiac Sarcoidosis in Japanese},

author = {Yasuyuki Honda and Toshiyuki Nagai and Yoshihiko Ikeda and Mamoru Sakakibara and Naoya Asakawa and Nobutaka Nagano and Michikazu Nakai and Kunihiro Nishimura and Yasuo Sugano and Keiko Ohta-Ogo and Yasuhide Asaumi and Takeshi Aiba and Hideaki Kanzaki and Kengo Kusano and Teruo Noguchi and Satoshi Yasuda and Hiroyuki Tsutsui and Hatsue Ishibashi-Ueda and Toshihisa Anzai},

doi = {10.1161/JAHA.116.004019},

issn = {2047-9980},

year  = {2016},

date = {2016-11-01},

urldate = {2016-11-01},

journal = {J Am Heart Assoc},

volume = {5},

number = {11},

abstract = {BACKGROUND: The histological diagnosis of cardiac sarcoidosis (CS) is based on the presence of myocardial granulomas; however, the sensitivity of endomyocardial biopsy is relatively low. We investigated whether immunocompetent cells including dendritic cells (DC) and macrophages in nongranuloma sections of endomyocardial biopsy samples could be histopathological surrogates for CS diagnosis.nnMETHODS AND RESULTS: The numbers of DC and macrophages were investigated in 95 consecutive CS patients and 50 patients with nonischemic cardiomyopathy as controls. All patients underwent endomyocardial biopsy, and immunohistochemical staining was performed on all samples. We examined these immunocompetent cells in nongranuloma sections in CS patients diagnosed by the presence of myocardial granulomas (n=26) and in CS patients without myocardial granulomas diagnosed by the Japanese Ministry of Health Welfare 2007 criteria (n=65) or the Heart Rhythm Society 2014 criteria (n=26). In CS patients with and without myocardial granulomas, CD209 DC and CD68 macrophages were more frequently observed (P<0.01) and CD163M2 macrophages were less frequently observed (P<0.01) in nongranuloma sections compared to controls. Furthermore, the combination of decreased CD163M2/CD68 macrophage ratio and increased number of CD209 DC in nongranuloma sections of CS patients demonstrated high specificity (100%, 95% CI 92.7-100) for CS diagnosis with each diagnostic criteria and the presence of myocardial granulomas.nnCONCLUSIONS: Increased number of DC and decreased M2 among all macrophages in nongranuloma sections of myocardium showed high specificity for CS diagnosis, suggesting DC and macrophage phenotypes as histopathological surrogates for the diagnosis of CS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27126377,

title = {Prognostic significance of endogenous erythropoietin in long-term outcome of patients with acute decompensated heart failure},

author = {Toshiyuki Nagai and Kunihiro Nishimura and Takehiro Honma and Aya Higashiyama and Yasuo Sugano and Michikazu Nakai and Satoshi Honda and Naotsugu Iwakami and Atsushi Okada and Shoji Kawakami and Tomoaki Kanaya and Yasuhide Asaumi and Takeshi Aiba and Yoko Nishida and Yoshimi Kubota and Daisuke Sugiyama and Tomonori Okamura and Teruo Noguchi and Kengo Kusano and Hisao Ogawa and Satoshi Yasuda and Toshihisa Anzai},

doi = {10.1002/ejhf.537},

issn = {1879-0844},

year  = {2016},

date = {2016-07-01},

urldate = {2016-07-01},

journal = {Eur J Heart Fail},

volume = {18},

number = {7},

pages = {803--813},

abstract = {AIMS: Although previous reports suggest that an elevated endogenous erythropoietin (EPO) level is associated with worse clinical outcomes in chronic heart failure (HF) patients, the prognostic implication of EPO in patients with acute decompensated HF (ADHF) and underlying mechanisms of the high EPO level in severe HF patients who have a poor prognosis remain unclear.nnMETHODS AND RESULTS: We examined 539 consecutive ADHF patients with EPO measurement on admission from our registry. During a median follow-up period of 329 days, a higher EPO level on admission was independently associated with worse clinical outcomes [hazard ratio (HR) 1.25, 95% confidence interval (CI) 1.06-1.48, P = 0.008], and haemoglobin level was the strongest determinant of EPO level (P < 0.001), whereas estimated glomerular filtration rate (eGFR) was not significant in multivariate regression analysis. In the anaemic subgroup of 318 patients, a higher EPO level than expected on the basis of their haemoglobin level was related to increased adverse events (HR 1.63, 95% CI 1.05-2.49, P = 0.028). Moreover, estimated plasma volume excess rate was positively associated with EPO level (P = 0.003), and anaemic patients with a higher than expected EPO level tended to have a higher estimated plasma volume excess rate and plasma lactate level, and lower systemic oxygen saturation level with the preservation of the reticulocyte production index than those with a lower than expected EPO level.nnCONCLUSION: A high EPO level predicts long-term worse clinical outcomes in ADHF patients, independent of anaemia and impaired renal function. Anaemia and hypoxia due to severe congestion may synergistically contribute to a high EPO level in high-risk HF patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24853830,

title = {Incidence and prognostic significance of myocardial late gadolinium enhancement in patients with sarcoidosis without cardiac manifestation},

author = {Toshiyuki Nagai and Shun Kohsaka and Shigeo Okuda and Toshihisa Anzai and Koichiro Asano and Keiichi Fukuda},

doi = {10.1378/chest.14-0139},

issn = {1931-3543},

year  = {2014},

date = {2014-10-01},

urldate = {2014-10-01},

journal = {Chest},

volume = {146},

number = {4},

pages = {1064--1072},

abstract = {BACKGROUND: Cardiac death is the leading cause of mortality associated with sarcoidosis in Japan. However, the involvement of sarcoidosis infiltration often remains undetected. Recently, late gadolinium enhancement with cardiovascular MRI (LGE-CMR) imaging has been introduced for the detection of myocardial infiltrative disease, as it enables the detection of even minor myocardial damage. We investigated the incidence and prognostic value of LGE-CMR in patients with extracardiac sarcoidosis without cardiac manifestations.nnMETHODS: Sixty-one consecutive patients who met the histologic and clinical criteria for sarcoidosis, and who did not have signs or symptoms of cardiovascular involvement, were prospectively recruited. LGE-CMR was performed at the time of enrollment, and patients were classified into positive or negative late gadolinium enhancement groups based on the findings. The study end point was a composite of all-cause death, symptomatic arrhythmia, and heart failure necessitating admission.nnRESULTS: Patients were predominantly middle aged (57 ± 15 years) and female (66%), and most had stable disease activity that did not require treatment with immunosuppressants. LGE-CMR detected cardiac involvement in eight patients (13%). Interventricular septal thinning detected by echocardiography was an independent predictor of LGE-CMR-detected cardiac involvement. During the follow-up period of 50 ± 12 months, no significant difference in adverse events was noted between patients in the LGE-CMR-positive and LGE-CMR-negative groups.nnCONCLUSIONS: LGE-CMR detected cardiac involvement in 13% of patients with sarcoidosis without cardiac manifestation, but both patients with and without LGE had relatively low event rates.nnTRIAL REGISTRY: Japan Primary Registries Network; No.: UMIN000001549; URL: www.umin.ac.jp.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}