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Prognostic Impacts of Plasma Levels of Cyclophilin A in Patients with Heart Failure
S60 Journal of Cardiac Failure Vol. 23 No. 10S October 2017 O49-4 Beneficial Effects of Early Cardiac Rehabilitation under Left Ventricular Assist System in a Patient with Peripartum Cardiomyopathy: Case Report Kentaro Kiryu1, Genbu Yamaura1, Takayuki Kadohama1, Yoshihumi Chida1, Fuminobu Tanaka1, Daichi Takagi1, Yoshinori Itagaki1, Hiroshi Yamamoto1, Hiroshi Ito2, Shunei Kyo3; 1Department of Vascular Surgery, Akita University Hospital, Akita, Japan; 2 Department of Cardiovascular and Respiratory Medicine, Akita University Hospital, Akita, Japan; 3Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan Peripartum cardiomyopathy (PPCM) has been reported to have a relatively high mortality (4–30%). We report a PPCM patient with left ventricular assist system (LVAS) who was able to weaning LVAS due to early cardiac rehabilitation under treatments of a βblocker and an antiprolactin agent. Case: A 32-year-old woman with no abnormalities during the course of a pregnancy presented yellow nasal discharge, cough, and dyspnea 24 days after delivery, and she was hospitalized with a diagnosis of acute congestive heart failure, followed by receiving catecholamine treatment and mechanical circulatory support (IABP and PCPS) under intratracheal ventilation. Seven days after hospitalization, extracorporeal LVAS (Nipro) was initiated because of refractory heart failure. Myocardial tissue biopsy revealed PPCM. Under treatments of a βblocker and an antiprolactin agent, cardiac rehabilitation started under on POD 18, thereafter cardiac function (LV ejection fraction; appearance of aortic valve opening) and BNP gradually improved. Based on satisfactory results of the off test and CPX, the patient weaned from LVAS on POD 170. LVEF and BNP were 15.4% and 1839.5 pg/ml, respectively, at hospital admission and were 45.5% and 55.4 pg/ml, respectively, at hospital discharge (total hospital stay: 203 days). Conclusion: Our experience suggests that early cardiac rehabilitation under treatments of βblockers and antiprolactin agents may have a beneficial effect in PPCM patients requiring an LVAS support.
29 ± 9 mmHg (P = .11), 8 ± 4 to 8 ± 4 mm (P = 1.0) in NMES group. Conclusions: This results suggest that the NMES can be feasible and safely realized in AHF patients.
O50-3 Safety and Efficacy of Waon Therapy for Patients with Severe Aortic Valve Stenosis treated by Transcatheter Aortic Valve Implantation Mitsuo Sobajima1, Hiroshi Onoda1, Hiroyuki Kuwahara1, Syuhei Tanaka1, Ryuichi Ushijima1, Nobuyuki Fukuda1, Hiroshi Ueno1, Koichiro Kinugawa1,2; 1The Second Department of Internal Medicine, University of Toyama, Toyama, Japan; 2The First Department of Surgery, University of Toyama, Toyama, Japan Backgrounds: Transcatheter aortic valve implantation (TAVI) has increasingly been indicated among elderly frail patients. Periprocedural cardiac rehabilitation cannot be emphasized too much, but many of them are difficult to ride ergometer. In contrast, Waon therapy (WT) needs little physical load, and can be performed in such frail patients. WT is currently contraindicated for untreated severe aortic valve stenosis (AS). We investigated the safety and efficacy of WT for severe AS patients who received TAVI. Methods: We enrolled consecutive 20 patients (age 84.8 ± 4.8 yo, CSHA frailty scale 3.7 ± 0.9) with severe AS treated by transfemoral TAVI. They were assigned to WT group (n = 10) and control group (n = 10). WT was performed for 2 weeks after TAVI. Results: After 2 weeks of TAVI, 6 minute walk distance (228 ± 109 to 291 ± 82 M, P < .05), log NTproBNP (3.39 ± 0.58 to 2.88 ± 0.52 pg/dl, P < .01), and cardio thoracic ratio (59 ± 7 to 55 ± 6%, P < .01) were significantly improved as compared to before TAVI in WT group, but not in control group. No complication was observed in either group. Conclusions: WT safely improves exercise capacity in patients received TAVI. WT may be useful for frail patients in place of cardiac rehabilitation.
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O51-1
Abnormal Blood Pressure Response to Exercise and Exercise Tolerance in Patients with Stable Heart Failure Hirofumi Kawamata1, Tatsuya Kawasaki1, Kenichi Kasai2, Shingo Hashimoto2, Ayumi Shirota1, Chieko Sakai1, Kuniyasu Harimoto1, Shigeyuki Miki1, Tadaaki Kamitani1; 1 Department of Cardiology, Matsushita Memorial Hospital, Japan; 2Department of Rehabilitation, Matsushita Memorial Hospital, Japan
Serum Uric Acid Increase through the Treatment of Acute Decompensated Heart Failure Might Predict Adverse Outcome Yuji Nagatomo1, Hironori Yamamoto2, Mayuko Tsugu1, Keitaro Mahara1, Mitsuaki Isobe1, Shun Kosaka3, Tsutomu Yoshikawa1; 1Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan; 2Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine; 3Department of Cardiology, Keio University School of Medicine
Background: Abnormal blood pressure (BP) response to exercise is often observed and reported to be associated with adverse cardiac events in patients with coronary artery disease. Reduced exercise tolerance is an independent predictor of adverse cardiac events in patient with heart failure (HF), but few data are available regarding the relation between exercise tolerance and abnormal BP response to exercise. Method: A total of 81 patients with stable HF underwent a symptom-limited cardiopulmonary exercise test. BP was noninvasively measured at an interval of one minute, and considered abnormal when exercise-induced increases in systolic BP were less than 25 mmHg. Exercise tolerance was evaluated with peak oxygen uptake (peak VO2). Result: The peak VO2 was 18.3 ± 4.8 ml/kg/min in all the patients. Abnormal BP response to exercise was observed in 29 patients (36%). There were no significant differences in resting BP and heart rate between the two groups. The peak VO2 was significantly lower in patients with abnormal BP response (15.9 ± 3.7 ml/kg/min) than in patients without abnormal BP response (19.7 ± 4.8 ml/kg/min, P < .05). Conclusions: Abnormal BP response to exercise was associated with reduced exercise tolerance in patients with stable HF. Further study is warranted to examine whether abnormal BP response is associated with adverse cardiac events in patients with stable HF.
O50-2 Neuromuscular Electrical Stimulation Is Feasible and Safely Realized in Acute Heart Failure Patients Toru Kondo1, Sumio Yamada2, Takahiro Okumura1, Etsuo Iwata3, Sayano Kondo3, Hiroaki Hiraiwa1, Daisuke Tanimura3, Toshiaki Kato3, Yoshifumi Awaji3, Toyoaki Murohara1; 1Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan; 2Department of Rehabilitation Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; 3Department of Cardiology, Nagoya Ekisaikai Hospital, Nagoya, Japan Background: Heart failure patients are inclined to protein catabolism and physical function declines progressively especially during hospitalization. Neuromuscular electrical stimulation (NMES) is known to preserve muscle mass and improve functional outcomes. We aimed to clarify the feasibility and safety of NMES in acute heart failure (AHF) patients. Methods: 73 AHF patients were randomly assigned to NMES group (n = 34) or control group (n = 39). NMES session were performed 5 days per week and the intensity of stimulation in controls was regulated not to induce effective muscle contractions. Results: 30 patients in NMES group and 34 patients in control group (87%) completed planned NMES sessions during hospitalization. Blood pressure and heart rate did not change significantly and new onset arrhythmia did not occur during NMES in both groups. Two patients showed lethal ventricular arrhythmia and one patient died in control group during hospitalization, however these events were not observed in NMES group. Intracardiac electrocardiogram showed no electromagnetic interference in the patients with pacemaker or implantable cardioverter defibrillator. Changes in tricuspid valve pressure gradiant and estimated right atrial pressure immediately before and after NMES were 27 ± 7 to
Background: Elevated serum uric acid (UA) is associated with an increased risk of adverse outcome in patients with chronic heart failure (CHF), however it remains still unknown whether the change of serum UA level predicts adverse events in CHF patients. Objective: The purpose of this study was to determine if in-hospital UA increase, after stabilization of acute decompensated HF (ADHF) predicts adverse events. Methods and Results: We retrospectively analyzed consecutive 492 patients who were hospitalized for ADHF, and their attending physicians evaluated UA levels at the hospitalization and before discharge. We followed them up until they had composite endpoint of rehospitalization for ADHF or death for the first time after discharge. UA levels both at admission and at discharge were available in 292 patients. UA values increased (I group) in 92 patients and it decreased in the remaining 200 patients (D group). At hospitalization I group were significantly older (77.6 ± 11.0 vs. 73.0 ± 12.7 years old, P < .0001) and their hemoglobin and serum UA level were significantly lower than D group (hemoglobin, 11.7 ± 1.9 vs. 12.4 ± 2.4 g/dl, P = .0008; UA, 6.0 ± 1.6 vs. 7.7 ± 2.1 mg/ dl, P < .0001 respectively) . UA increase was associated with higher incidence of endpoint (38.0% vs. 30.5%, P = .0487, log-rank test). Conclusion: In CHF patients, increase of UA through the treatment of ADHF might predict adverse outcome.
O51-2 Prognostic Impacts of Plasma Levels of Cyclophilin A in Patients with Heart Failure Tomohiro Ohtsuki, Kimio Satoh, Nobuhiro Yaoita, Junichi Omura, Nobuhiro Kikuchi, Ryo Kurosawa, Shinichiro Sunamura, Masamichi Nogi, Satoshi Miyata, Hiroaki Shimokawa; Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background: Cyclophilin A (CyPA) is secreted from cardiac fibroblasts in response to angiotensin II or mechanical stretch and promotes cardiac hypertrophy, fibrosis and the development of arteriosclerosis. However, the role of CyPA as a biomarker for patients with heart failure (HF) remains to be elucidated. Methods and Results: In 175 consecutive patients who were hospitalized in Tohoku University Hospital for HF, we measured plasma levels of CyPA and BNP and examined their prognostic impacts during the followup (median 5.8 years). Plasma CyPA levels were significantly elevated in HF patients (15.1 ± 9.8 ng/mL, n = 175) than in healthy controls (3.3 ± 2.2 ng/mL, n = 10, P < .001). Kaplan-Meier curve showed that higher CyPA levels (≥10 ng/mL) were associated with all-cause death (HR4.3, 95%CI:1.5–12.4, P < .01) and rehospitalization (HR2.6 95%CI:1.1– 6.3, P < .05). Higher BNP levels (≥100 pg/mL) were also associated with all-cause death (HR2.4, 95%CI:1.2–5.1, P < .05) and rehospitalization (HR3.2, 95%CI:1.5–7.2, P < .01). Interestingly, there was no correlation between CyPA and BNP levels, suggesting different clinical implications of the 2 biomarkers. Importantly, the combination of CyPA (≥10 ng/mL) and BNP (≥100 pg/mL) was highly significantly associated with all-cause death (HR4.7, 95%CI:1.4–15.6, P < .01) and rehospitalization (HR6.9, 95%CI:1.6– 29.3, P < .01) compared with CyPA (<10 ng/mL) or BNP (<100 pg/mL) alone. Conclusions:
The 21st Annual Scientific Meeting These results indicate that plasma CyPA levels have prognostic impacts in HF patients, which are further enhanced when combined with BNP.
O51-3 Human Epididymis Protein 4 Is a Novel Marker of Ongoing Cardiac Fibrosis and Predicts Pathologic Cardiac Remodeling in Dilated Cardiomyopathy Masahiro Yamamoto, Shinsuke Hanatani, Kyoko Hirakawa, Seiji Takashio, Yasuhiro Izumiya, Kenichi Tsujita; Cardiovascular Medicine, University of Kumamoto, Kumamoto, Japan Introduction: Interstitial fibrosis play a crucial role in the pathophysiology of dilated cardiomyopathy (DCM). Human epididymis protein 4 (HE-4) is a secreted protein that is expected to reflect ongoing-fibrosis. Hypothesis: In patients with DCM, HE-4 could be a useful biomarker to evaluate disease severity and predict future pathologic cardiac remodeling and cardiovascular events. Methods and Results: We measured serum HE-4 levels in 28 patients with DCM and followed the patients for echocardiography parameters and cardiovascular events. Cardiovascular events were defined as total death and cardiovascular hospitalization. Serum HE-4 concentrations were measured by ELISA. Median HE-4 level in all participants was 6189.6 pg/ml. Follow-up echocardiography revealed that circulating levels of HE-4 (ln[HE-4]) at study baseline was associated with the two-year variation of left ventricular systolic diameter (r = 0.44, P = .003) and left atrial diameter (r = 0.60, P = .003), indicators of cardiac pathological remodeling. They were divided into two groups according to the HE-4 level. Kaplan Meier curve revealed that the risk of adverse cardiovascular events was significantly greater in the high (>median) than low HE-4 group (log-rank test: P = .03). Univariate Cox hazard analysis identified HE-4 (hazard ratio: 10.92; 95% confidence interval: 1.44– 82.60, P = .021) as significant predictor of adverse events. Conclusions: HE-4, novel marker of ongoing-fibrosis, could be useful for evaluating disease severity and predicting future adverse cardiac remodeling and cardiovascular events in patients with DCM.
O51-4 Presepsin, Soluble CD14 Subtype, Is a Novel Marker of Short-term Mortality in Patients Hospitalized for Worsening Heart Failure Hideto Nishimura1, Junnichi Ishii2, Takashi Muramatsu1, Masahide Harada1, Sadako Motoyama1, Shigeru Matsui1, Hiroyuki Naruse2, Eiichi Watanabe1, Hideo Izawa3, Yukio Ozaki1; 1Department of Cardiology, Fujita Health University School of Medicine, Toyoake, Japan; 2Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University School of Medicine, Toyoake, Japan; 3Department of Cardiology, Banbuntane Houtokukai Hospital, Nagoya, Japan Presepsin, a subtype of soluble CD14, is an inflammatory marker, which largely reflects monocytic activation. We prospectively investigated the prognostic value of plasma presepsin concentration in 506 patients (mean age, 71 years) hospitalized for worsening heart failure. Results: Presesin levels significantly (P < .0001) correlated with estimated glomerular filtration rate (r = −0.42), N-terminal pro-B-type natriuretic peptide (r = 0.34), and high-sensitivity C-reactive protein (r = 0.36). During 6-month follow-up period, 53 deaths occurred, including 42 cardiovascular deaths. Using a multivariate Cox regression analysis including clinical, biochemical, and echocardiographic parameters, presepsin concentration was an independent predictor of 6-month mortality (P = .01). Patients with 3rd presepsin tertile had a higher risk for 6-month mortality than those with 1st or 2nd presepsin tertile (Figure). Conclusion: Presepsin may be a novel marker of short-term mortality in patients hospitalized for worsening heart failure.
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O51-5 Serial Changes of Serum ACE2 and Ang-(1-7) Concentration after Optimal Therapy for Acute Heart Failure Patients Requiring Emergency Hospitalization Shinji Hisatake, Shunsuke Kiuchi, Takayuki Kabuki, Takashi Oka, Takahiro Fujii, Shintaro Dobashi, Takanori Ikeda; Department of Cardiovascular Medicine, Toho University Omori Medical Center, Tokyo, Japan Background: We previously reported that acute heart failure (AHF) patients indicated high ACE2 and low Ang-(1-7) concentration (hereafter in serum) in acute phase, compared with healthy volunteers (HV). No studies have reported serial changes of ACE2 and Ang-(1-7) concentration after optimal therapy. Methods: This study enrolled 68 AHF patients. ACE2 and Ang-(1-7) concentration were measured in 3 timepoints: immediately after admission, 1 month and 3 months after optimal therapy (Month1 and Month3). Serial changes of those parameters were investigated and compared with the HV values. Results: Significant serial changes of ACE2 and Ang-(1-7) concentration were not observed. In acute phase, AHF patients exhibited significantly lower Ang-(1-7) concentration (2.40 ± 1.11 vs. 3.1 ± 1.1 ng/mL, respectively; P < .005), and significantly higher ACE2 concentration (7.45 ± 3.13 vs. 4.84 ± 2.25 ng/mL, respectively; P < .005) compared with HV. At Month1, AHF patients remained lower Ang(1-7) concentration compared with HV (2.37 ± 1.63 vs. 3.1 ± 1.1 ng/mL, respectively; P < .05), however there were no significant ACE2 concentration differences between AHF patients and HV (6.11 ± 3.36 vs. 4.84 ± 2.25 ng/mL, respectively; P = .167). Ang(1-7) and ACE2 concentration levels of AHF patients at Month3 indicated no significant differences, and were equivalent with HV, (3.03 ± 2.07 vs. 3.1 ± 1.1 ng/mL, respectively; P = .854, 6.10 ± 2.04 vs. 4.84 ± 2.25 ng/mL, respectively; P = .061). Conclusions: The concentration in AHF patients became equivalent with HV at Month1 and Month3 in ACE2, and at Month3 in Ang-(1-7).
O51-6 Serum Micro-ribonucleic Acid-126 and -223 as a New Generation Biomarker for Cardiac Sarcoidosis Wakata Fujiwara1, Ryo Yamada1, Tomoya Ishiguro1, Satoshi Okumura1, Masataka Yoshinaga1, Yoshinori Sugishita1, Mutsuharu Hayashi1, Yasuchika Kato1, Yukio Ozaki2, Hideo Izawa1; 1Fujita Health University Banbuntane Houtokukai Hospital; 2Fujita Health University Hospital Background: Cardiac sarcoidosis is associated with poor prognosis. Clinical manifestations of cardiac sarcoidosis are non-specific, and the sensitivity and specificity of diagnostic modalities are limited. Serum micro RNAs (miRNAs) has been recently reported as a new generation biomarkers for various diseases such as cancer, neurological diseases, and immune diseases. To date, little is known whether serum miRNAs could be useful as diagnostic biomarkers for cardiac sarcoidosis. Methods: We first performed a genome-wide expression profiling for a total of 389 miRNAs (HumanmiRNA ver.20) using peripheral blood samples of 5 patients with cardiac sarcoidosis (61 ± 9 years) and 3 healthy controls (54 ± 7 years). From this screening study, we selected 12 miRNAs which are significantly related to cardiac sarcoidosis. We then performed real-time PCR in blood samples from 15 new patients with cardiac sarcoidosis and 4 controls to quantify these 12 miRNAs expressions. Results: In the first screening study, 12 miRNAs were differentially expressed significantly (P < .01) in 5 patients with cardiac sarcoidosis compared with 3 controls. The real-time PCR in blood samples from 15 patients with cardiac sarcoidosis and 4 controls revealed that expressions of miRNA-126 and −223 were significantly increased in patients with cardiac sarcoidosis compared with controls analyzed by Mann-Whitney U test. Conclusion: We demonstrated that serum miRNA-126 and −223 could be a new generation diagnos biomarker for cardiac sarcoidosis.
O52-1 Prognostic Importance of Low Serum Chloride Levels in Patients with Acute Decompensated Heart Failure from COMCHEF Database Ryoto Horai, Masaaki Hoshiga, Kanako Akamatsu, Daichi Maeda, Kazushi Sakane, Michishige Ozeki, Tomohiro Fujisaka, Koichi Sohmiya, Nobukazu Ishizaka; Department of Cardiology, Osaka Medical College, Osaka, Japan Several recent studies suggest that serum chloride levels are related with the prognosis of patients with heart failure (HF). We investigated the prognostic importance of serum chloride in patients who were hospitalized due to acute decompensated heart failure (ADHF). The patients were sub-grouped by serum chloride levels: low chloride group who had chloride of <100 mEq/L (n = 32)(LCG) and normal/high group chloride of >100 mEq/L (n = 133)(N/HCG). During the median follow-up period of 208 days, 69 events, which comprised re-hospitalization due to worsening HF or death, occurred. Kaplan-Meier analysis revealed that LCG experienced events more frequently than N/HCG (86% versus 47%, log-rank P = .0003). In conclusion, among ADHF patients, serum chloride levels less than 100 mEq/L on admission are associated with increased event rate comprising re-hospitalization due to HF or death.
29 ± 9 mmHg (P = .11), 8 ± 4 to 8 ± 4 mm (P = 1.0) in NMES group. Conclusions: This results suggest that the NMES can be feasible and safely realized in AHF patients.
O50-3 Safety and Efficacy of Waon Therapy for Patients with Severe Aortic Valve Stenosis treated by Transcatheter Aortic Valve Implantation Mitsuo Sobajima1, Hiroshi Onoda1, Hiroyuki Kuwahara1, Syuhei Tanaka1, Ryuichi Ushijima1, Nobuyuki Fukuda1, Hiroshi Ueno1, Koichiro Kinugawa1,2; 1The Second Department of Internal Medicine, University of Toyama, Toyama, Japan; 2The First Department of Surgery, University of Toyama, Toyama, Japan Backgrounds: Transcatheter aortic valve implantation (TAVI) has increasingly been indicated among elderly frail patients. Periprocedural cardiac rehabilitation cannot be emphasized too much, but many of them are difficult to ride ergometer. In contrast, Waon therapy (WT) needs little physical load, and can be performed in such frail patients. WT is currently contraindicated for untreated severe aortic valve stenosis (AS). We investigated the safety and efficacy of WT for severe AS patients who received TAVI. Methods: We enrolled consecutive 20 patients (age 84.8 ± 4.8 yo, CSHA frailty scale 3.7 ± 0.9) with severe AS treated by transfemoral TAVI. They were assigned to WT group (n = 10) and control group (n = 10). WT was performed for 2 weeks after TAVI. Results: After 2 weeks of TAVI, 6 minute walk distance (228 ± 109 to 291 ± 82 M, P < .05), log NTproBNP (3.39 ± 0.58 to 2.88 ± 0.52 pg/dl, P < .01), and cardio thoracic ratio (59 ± 7 to 55 ± 6%, P < .01) were significantly improved as compared to before TAVI in WT group, but not in control group. No complication was observed in either group. Conclusions: WT safely improves exercise capacity in patients received TAVI. WT may be useful for frail patients in place of cardiac rehabilitation.
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Abnormal Blood Pressure Response to Exercise and Exercise Tolerance in Patients with Stable Heart Failure Hirofumi Kawamata1, Tatsuya Kawasaki1, Kenichi Kasai2, Shingo Hashimoto2, Ayumi Shirota1, Chieko Sakai1, Kuniyasu Harimoto1, Shigeyuki Miki1, Tadaaki Kamitani1; 1 Department of Cardiology, Matsushita Memorial Hospital, Japan; 2Department of Rehabilitation, Matsushita Memorial Hospital, Japan
Serum Uric Acid Increase through the Treatment of Acute Decompensated Heart Failure Might Predict Adverse Outcome Yuji Nagatomo1, Hironori Yamamoto2, Mayuko Tsugu1, Keitaro Mahara1, Mitsuaki Isobe1, Shun Kosaka3, Tsutomu Yoshikawa1; 1Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan; 2Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine; 3Department of Cardiology, Keio University School of Medicine
Background: Abnormal blood pressure (BP) response to exercise is often observed and reported to be associated with adverse cardiac events in patients with coronary artery disease. Reduced exercise tolerance is an independent predictor of adverse cardiac events in patient with heart failure (HF), but few data are available regarding the relation between exercise tolerance and abnormal BP response to exercise. Method: A total of 81 patients with stable HF underwent a symptom-limited cardiopulmonary exercise test. BP was noninvasively measured at an interval of one minute, and considered abnormal when exercise-induced increases in systolic BP were less than 25 mmHg. Exercise tolerance was evaluated with peak oxygen uptake (peak VO2). Result: The peak VO2 was 18.3 ± 4.8 ml/kg/min in all the patients. Abnormal BP response to exercise was observed in 29 patients (36%). There were no significant differences in resting BP and heart rate between the two groups. The peak VO2 was significantly lower in patients with abnormal BP response (15.9 ± 3.7 ml/kg/min) than in patients without abnormal BP response (19.7 ± 4.8 ml/kg/min, P < .05). Conclusions: Abnormal BP response to exercise was associated with reduced exercise tolerance in patients with stable HF. Further study is warranted to examine whether abnormal BP response is associated with adverse cardiac events in patients with stable HF.
O50-2 Neuromuscular Electrical Stimulation Is Feasible and Safely Realized in Acute Heart Failure Patients Toru Kondo1, Sumio Yamada2, Takahiro Okumura1, Etsuo Iwata3, Sayano Kondo3, Hiroaki Hiraiwa1, Daisuke Tanimura3, Toshiaki Kato3, Yoshifumi Awaji3, Toyoaki Murohara1; 1Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan; 2Department of Rehabilitation Science, Nagoya University Graduate School of Medicine, Nagoya, Japan; 3Department of Cardiology, Nagoya Ekisaikai Hospital, Nagoya, Japan Background: Heart failure patients are inclined to protein catabolism and physical function declines progressively especially during hospitalization. Neuromuscular electrical stimulation (NMES) is known to preserve muscle mass and improve functional outcomes. We aimed to clarify the feasibility and safety of NMES in acute heart failure (AHF) patients. Methods: 73 AHF patients were randomly assigned to NMES group (n = 34) or control group (n = 39). NMES session were performed 5 days per week and the intensity of stimulation in controls was regulated not to induce effective muscle contractions. Results: 30 patients in NMES group and 34 patients in control group (87%) completed planned NMES sessions during hospitalization. Blood pressure and heart rate did not change significantly and new onset arrhythmia did not occur during NMES in both groups. Two patients showed lethal ventricular arrhythmia and one patient died in control group during hospitalization, however these events were not observed in NMES group. Intracardiac electrocardiogram showed no electromagnetic interference in the patients with pacemaker or implantable cardioverter defibrillator. Changes in tricuspid valve pressure gradiant and estimated right atrial pressure immediately before and after NMES were 27 ± 7 to
Background: Elevated serum uric acid (UA) is associated with an increased risk of adverse outcome in patients with chronic heart failure (CHF), however it remains still unknown whether the change of serum UA level predicts adverse events in CHF patients. Objective: The purpose of this study was to determine if in-hospital UA increase, after stabilization of acute decompensated HF (ADHF) predicts adverse events. Methods and Results: We retrospectively analyzed consecutive 492 patients who were hospitalized for ADHF, and their attending physicians evaluated UA levels at the hospitalization and before discharge. We followed them up until they had composite endpoint of rehospitalization for ADHF or death for the first time after discharge. UA levels both at admission and at discharge were available in 292 patients. UA values increased (I group) in 92 patients and it decreased in the remaining 200 patients (D group). At hospitalization I group were significantly older (77.6 ± 11.0 vs. 73.0 ± 12.7 years old, P < .0001) and their hemoglobin and serum UA level were significantly lower than D group (hemoglobin, 11.7 ± 1.9 vs. 12.4 ± 2.4 g/dl, P = .0008; UA, 6.0 ± 1.6 vs. 7.7 ± 2.1 mg/ dl, P < .0001 respectively) . UA increase was associated with higher incidence of endpoint (38.0% vs. 30.5%, P = .0487, log-rank test). Conclusion: In CHF patients, increase of UA through the treatment of ADHF might predict adverse outcome.
O51-2 Prognostic Impacts of Plasma Levels of Cyclophilin A in Patients with Heart Failure Tomohiro Ohtsuki, Kimio Satoh, Nobuhiro Yaoita, Junichi Omura, Nobuhiro Kikuchi, Ryo Kurosawa, Shinichiro Sunamura, Masamichi Nogi, Satoshi Miyata, Hiroaki Shimokawa; Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background: Cyclophilin A (CyPA) is secreted from cardiac fibroblasts in response to angiotensin II or mechanical stretch and promotes cardiac hypertrophy, fibrosis and the development of arteriosclerosis. However, the role of CyPA as a biomarker for patients with heart failure (HF) remains to be elucidated. Methods and Results: In 175 consecutive patients who were hospitalized in Tohoku University Hospital for HF, we measured plasma levels of CyPA and BNP and examined their prognostic impacts during the followup (median 5.8 years). Plasma CyPA levels were significantly elevated in HF patients (15.1 ± 9.8 ng/mL, n = 175) than in healthy controls (3.3 ± 2.2 ng/mL, n = 10, P < .001). Kaplan-Meier curve showed that higher CyPA levels (≥10 ng/mL) were associated with all-cause death (HR4.3, 95%CI:1.5–12.4, P < .01) and rehospitalization (HR2.6 95%CI:1.1– 6.3, P < .05). Higher BNP levels (≥100 pg/mL) were also associated with all-cause death (HR2.4, 95%CI:1.2–5.1, P < .05) and rehospitalization (HR3.2, 95%CI:1.5–7.2, P < .01). Interestingly, there was no correlation between CyPA and BNP levels, suggesting different clinical implications of the 2 biomarkers. Importantly, the combination of CyPA (≥10 ng/mL) and BNP (≥100 pg/mL) was highly significantly associated with all-cause death (HR4.7, 95%CI:1.4–15.6, P < .01) and rehospitalization (HR6.9, 95%CI:1.6– 29.3, P < .01) compared with CyPA (<10 ng/mL) or BNP (<100 pg/mL) alone. Conclusions:
The 21st Annual Scientific Meeting These results indicate that plasma CyPA levels have prognostic impacts in HF patients, which are further enhanced when combined with BNP.
O51-3 Human Epididymis Protein 4 Is a Novel Marker of Ongoing Cardiac Fibrosis and Predicts Pathologic Cardiac Remodeling in Dilated Cardiomyopathy Masahiro Yamamoto, Shinsuke Hanatani, Kyoko Hirakawa, Seiji Takashio, Yasuhiro Izumiya, Kenichi Tsujita; Cardiovascular Medicine, University of Kumamoto, Kumamoto, Japan Introduction: Interstitial fibrosis play a crucial role in the pathophysiology of dilated cardiomyopathy (DCM). Human epididymis protein 4 (HE-4) is a secreted protein that is expected to reflect ongoing-fibrosis. Hypothesis: In patients with DCM, HE-4 could be a useful biomarker to evaluate disease severity and predict future pathologic cardiac remodeling and cardiovascular events. Methods and Results: We measured serum HE-4 levels in 28 patients with DCM and followed the patients for echocardiography parameters and cardiovascular events. Cardiovascular events were defined as total death and cardiovascular hospitalization. Serum HE-4 concentrations were measured by ELISA. Median HE-4 level in all participants was 6189.6 pg/ml. Follow-up echocardiography revealed that circulating levels of HE-4 (ln[HE-4]) at study baseline was associated with the two-year variation of left ventricular systolic diameter (r = 0.44, P = .003) and left atrial diameter (r = 0.60, P = .003), indicators of cardiac pathological remodeling. They were divided into two groups according to the HE-4 level. Kaplan Meier curve revealed that the risk of adverse cardiovascular events was significantly greater in the high (>median) than low HE-4 group (log-rank test: P = .03). Univariate Cox hazard analysis identified HE-4 (hazard ratio: 10.92; 95% confidence interval: 1.44– 82.60, P = .021) as significant predictor of adverse events. Conclusions: HE-4, novel marker of ongoing-fibrosis, could be useful for evaluating disease severity and predicting future adverse cardiac remodeling and cardiovascular events in patients with DCM.
O51-4 Presepsin, Soluble CD14 Subtype, Is a Novel Marker of Short-term Mortality in Patients Hospitalized for Worsening Heart Failure Hideto Nishimura1, Junnichi Ishii2, Takashi Muramatsu1, Masahide Harada1, Sadako Motoyama1, Shigeru Matsui1, Hiroyuki Naruse2, Eiichi Watanabe1, Hideo Izawa3, Yukio Ozaki1; 1Department of Cardiology, Fujita Health University School of Medicine, Toyoake, Japan; 2Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University School of Medicine, Toyoake, Japan; 3Department of Cardiology, Banbuntane Houtokukai Hospital, Nagoya, Japan Presepsin, a subtype of soluble CD14, is an inflammatory marker, which largely reflects monocytic activation. We prospectively investigated the prognostic value of plasma presepsin concentration in 506 patients (mean age, 71 years) hospitalized for worsening heart failure. Results: Presesin levels significantly (P < .0001) correlated with estimated glomerular filtration rate (r = −0.42), N-terminal pro-B-type natriuretic peptide (r = 0.34), and high-sensitivity C-reactive protein (r = 0.36). During 6-month follow-up period, 53 deaths occurred, including 42 cardiovascular deaths. Using a multivariate Cox regression analysis including clinical, biochemical, and echocardiographic parameters, presepsin concentration was an independent predictor of 6-month mortality (P = .01). Patients with 3rd presepsin tertile had a higher risk for 6-month mortality than those with 1st or 2nd presepsin tertile (Figure). Conclusion: Presepsin may be a novel marker of short-term mortality in patients hospitalized for worsening heart failure.
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O51-5 Serial Changes of Serum ACE2 and Ang-(1-7) Concentration after Optimal Therapy for Acute Heart Failure Patients Requiring Emergency Hospitalization Shinji Hisatake, Shunsuke Kiuchi, Takayuki Kabuki, Takashi Oka, Takahiro Fujii, Shintaro Dobashi, Takanori Ikeda; Department of Cardiovascular Medicine, Toho University Omori Medical Center, Tokyo, Japan Background: We previously reported that acute heart failure (AHF) patients indicated high ACE2 and low Ang-(1-7) concentration (hereafter in serum) in acute phase, compared with healthy volunteers (HV). No studies have reported serial changes of ACE2 and Ang-(1-7) concentration after optimal therapy. Methods: This study enrolled 68 AHF patients. ACE2 and Ang-(1-7) concentration were measured in 3 timepoints: immediately after admission, 1 month and 3 months after optimal therapy (Month1 and Month3). Serial changes of those parameters were investigated and compared with the HV values. Results: Significant serial changes of ACE2 and Ang-(1-7) concentration were not observed. In acute phase, AHF patients exhibited significantly lower Ang-(1-7) concentration (2.40 ± 1.11 vs. 3.1 ± 1.1 ng/mL, respectively; P < .005), and significantly higher ACE2 concentration (7.45 ± 3.13 vs. 4.84 ± 2.25 ng/mL, respectively; P < .005) compared with HV. At Month1, AHF patients remained lower Ang(1-7) concentration compared with HV (2.37 ± 1.63 vs. 3.1 ± 1.1 ng/mL, respectively; P < .05), however there were no significant ACE2 concentration differences between AHF patients and HV (6.11 ± 3.36 vs. 4.84 ± 2.25 ng/mL, respectively; P = .167). Ang(1-7) and ACE2 concentration levels of AHF patients at Month3 indicated no significant differences, and were equivalent with HV, (3.03 ± 2.07 vs. 3.1 ± 1.1 ng/mL, respectively; P = .854, 6.10 ± 2.04 vs. 4.84 ± 2.25 ng/mL, respectively; P = .061). Conclusions: The concentration in AHF patients became equivalent with HV at Month1 and Month3 in ACE2, and at Month3 in Ang-(1-7).
O51-6 Serum Micro-ribonucleic Acid-126 and -223 as a New Generation Biomarker for Cardiac Sarcoidosis Wakata Fujiwara1, Ryo Yamada1, Tomoya Ishiguro1, Satoshi Okumura1, Masataka Yoshinaga1, Yoshinori Sugishita1, Mutsuharu Hayashi1, Yasuchika Kato1, Yukio Ozaki2, Hideo Izawa1; 1Fujita Health University Banbuntane Houtokukai Hospital; 2Fujita Health University Hospital Background: Cardiac sarcoidosis is associated with poor prognosis. Clinical manifestations of cardiac sarcoidosis are non-specific, and the sensitivity and specificity of diagnostic modalities are limited. Serum micro RNAs (miRNAs) has been recently reported as a new generation biomarkers for various diseases such as cancer, neurological diseases, and immune diseases. To date, little is known whether serum miRNAs could be useful as diagnostic biomarkers for cardiac sarcoidosis. Methods: We first performed a genome-wide expression profiling for a total of 389 miRNAs (HumanmiRNA ver.20) using peripheral blood samples of 5 patients with cardiac sarcoidosis (61 ± 9 years) and 3 healthy controls (54 ± 7 years). From this screening study, we selected 12 miRNAs which are significantly related to cardiac sarcoidosis. We then performed real-time PCR in blood samples from 15 new patients with cardiac sarcoidosis and 4 controls to quantify these 12 miRNAs expressions. Results: In the first screening study, 12 miRNAs were differentially expressed significantly (P < .01) in 5 patients with cardiac sarcoidosis compared with 3 controls. The real-time PCR in blood samples from 15 patients with cardiac sarcoidosis and 4 controls revealed that expressions of miRNA-126 and −223 were significantly increased in patients with cardiac sarcoidosis compared with controls analyzed by Mann-Whitney U test. Conclusion: We demonstrated that serum miRNA-126 and −223 could be a new generation diagnos biomarker for cardiac sarcoidosis.
O52-1 Prognostic Importance of Low Serum Chloride Levels in Patients with Acute Decompensated Heart Failure from COMCHEF Database Ryoto Horai, Masaaki Hoshiga, Kanako Akamatsu, Daichi Maeda, Kazushi Sakane, Michishige Ozeki, Tomohiro Fujisaka, Koichi Sohmiya, Nobukazu Ishizaka; Department of Cardiology, Osaka Medical College, Osaka, Japan Several recent studies suggest that serum chloride levels are related with the prognosis of patients with heart failure (HF). We investigated the prognostic importance of serum chloride in patients who were hospitalized due to acute decompensated heart failure (ADHF). The patients were sub-grouped by serum chloride levels: low chloride group who had chloride of <100 mEq/L (n = 32)(LCG) and normal/high group chloride of >100 mEq/L (n = 133)(N/HCG). During the median follow-up period of 208 days, 69 events, which comprised re-hospitalization due to worsening HF or death, occurred. Kaplan-Meier analysis revealed that LCG experienced events more frequently than N/HCG (86% versus 47%, log-rank P = .0003). In conclusion, among ADHF patients, serum chloride levels less than 100 mEq/L on admission are associated with increased event rate comprising re-hospitalization due to HF or death.