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AT1 Receptor Activated by Toll Like Receptor 4 in the Brainstem Causes Sympathoexcitation in Mice With Heart Failure
S168 Journal of Cardiac Failure Vol. 16 No. 9S September 2010 irreversibly impaired in a small number of patients and these patients may need cardiac transplantation.
114 Cardiac Resynchronaization Therapy Enables to Reinforce Medication With Beta-Blocker and ACE-I, and Reduse a Risk of Rehospitalization SHINSUKE IWAI1, JUNICHI NITTA1, KENSUKE IHARA1, MITSUTOSHI ASANO1, AKIRA SATO1, TSUNEHIRO YAMATO1, YUTAKA MATSUMURA1, KAZUYASU TAKEI1, KIHIRO ASAKAWA1, MITSUAKI ISOBE2 1 Cardiovascular Medicine, Saitama Red Cross Hospital, Saitama, Japan, 2Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan The first case, a 71-year-old man complained of dyspnea, and repeated rehospitalization due to congestive heart failure by dialated cardiomyopathy. It was difficult to taper catecholamine. Electrocardiogram on admission showed CLBBB with wide QRS, and echocardiography showed diffuse hypokinetic left ventricular wall motion(ejection fraction 27%)with interventricular dyssynchrony. After implantation of CRT-D, we successed to taper catecholamine, introduce ACE-I(Perindopril 4mg/day), and increase dose of beta-blocker(Carvedilol 5mg to 20mg/day) while decrease diuretics. Hyponatremia was improved by decreasing diuretics. For a follow up period, he was not need to be admitted to hospital. BNP levels decreased from 1356 to 566 pg/ml. The second case, a 81-year-old man with congestive heart failure by dialated cardiomyopathy, who repeated rehospitalization and it was difficult to get out of the hospital. Electrocardiogram showed CLBBB with wide QRS, and echocardiography showed diffuse hypokinetic left ventricular wall motion with interventricular dyssynchrony. After implantation of CRT-D, we successed to taper catecholamine, introduce ACE-I(Perindopril 2mg/day), and increase dose of beta-blocker(Carvedilol 7.5mg to 10mg/day). For a follow up period, he was admitted to a hospital twice but we could reduce hospital time and prolong intervals to hospitalization. We report two cases that Cardiac resynchronaization therapy enabled to reinforce medication with betablocker and ACE-I, and reduse a risk of rehospitalization and hospital time.
115 A Case of Restoration of Cardiac Function Within a Few Months Treated as DCM for More than 8 Years TORU OGAWA, YASUHIRO SATOH, RYUICHI KATO, MASAHIRO SEKIGAWA, MASAAKI SHOJI, YUJI KONISHI, JUNKO ITO, KAORU SAKURAI, YASUHIRO YOKOYAMA, TAKASHI ASHIKAGA The Department of Cardiology, National Hospital Organization Disaster Medical Center, Tokyo, Japan Forty-two years old male complained of exertional dyspnea and was admitted into our ward. His past history was hypertension, diabetes mellitus at 34 years old. At that point poor LV function was pointed out and catheterization study was done. No coronary lesion was revealed with severely impaired LV wall motion. He was diagnosed as dilated cardiomyopathy, although not typical, and he was treated by digitalis, beta blockade and ARB in the outpatient clinic since then. He was readmitted due to the above symptom on December 2009. Two weeks prior to admission, he had fever and cough treated by antibiotics. Transthoracic echocardiography showed balllike mobile thrombus (402017mm) in LV. LV ejection fraction was 36% and BNP was 1100 pg/ml. Heparin administration followed by warfarinization was started and finally thrombus disappeared without complication. Together with thrombus resolution (2010 February) LV function restored from 36% to 62%. BNP level returned to normal (11.1). Conclusion: LV function in DCM was not supposed to restore especially in a short period. Since this patient suffered from infection before the worsening of cardiac symptom, infection of myocardial involvement might play an important role on the mechanism of LV function reversibility.
116 Defective Calmodulin Binding to RyR2 Renders the Ca2+ Release Channel Leaky in Failing Hearts AKIHIRO HINO, MASAFUMI YANO, TAKESHI SUETOMI, MAKOTO ONO, XIAOJUAN XU, HITOSHI UCHINOUMI, MASAHIRO DOI, SHINICHI OKUDA, SHIGEKI KOBAYASHI, TAKESHI YAMAMOTO Yamaguchi Univ Graduate Sch of Med, Ube, Japan
failing cells. Addition of DPc10 (10 mM), which was found to induce domain unzipping mimicking failing SR, to normal cells decreased the CaM binding. Conversely, the decreased CaM binding seen in failing cells was attenuated by addition of dantrolene (Dan), which was found to correct the defective N-C inter-domain interaction (i.e. domain unzipping to zipping). In saponin-permeabilized, failing cells, the frequency of Ca2+ sparks was markedly increased, whereas addition of either Dan or high concentration of CaM (1mM) inhibited the increase in SpF. Conclusions. The defective interdomain interaction between N-C domains within RyR2 reduces the CaM binding affinity to RyR2, subsequently increasing spontaneous Ca2+ release events in failing SR.
117 Biomarkers About Cardio-Renal Continuum, Serum CystatinC and Urine Micro Albumin Vary on the Course of Treatment Acute Heart Failure Syndrome SATOSHI KOYAMA1, YUKIHITO SATO1, MANA KAWASHIMA1, TAKUMA SAWA1, YOHEI TANADA1, ERIKA YAMAMOTO1, SAYAKA SAIJO1, TAKAKO FUJIWARA2, YOSHIKI TAKATSU1, HISAYOSHI FUJIWARA1 1 Department of cardiology, Hyogo prefectural Amagasaki Hospital, Amagasaki, Japan, 2Kyoto Women‘s university There are many reports about the effectiveness of cardiac biomarkers in the treatment of acute heart failure. We assessed urine micro albumin and serum cystatin C of the patients who required admission due to acute heart failure syndrome(n542) as a biomarkers of Cardio-renal Continuum. Blood and urine samples were collected from these patients on the admission day, 4th, 7th and 14th day after the admission. We assessed NT-pro BNP and Cardiac Troponin-T concurrently as biomarkers about cardiac failure. Patients were treated with vasodilator (nitroglycerin or hANP) with or without diuretics and inotropic agent at a physician‘s discretion.NT-pro BNP was decreased rapidly in response to the therapy(10014618497ng/ml, 525469704 ng/ml, 4893610726 ng/ml, 4381611028 ng/ml, admission day, the 4th,7th,14th day after admission respectively, p50.002), however Troponin T had a tendency for increase(0.03660.005 ng/ml, 0.03560.005 ng/ml, 0.03460.005 ng/ml, 0.03960.008 ng/ml as above, p50.50). Urine micro albumin significantly decreased in response to the therapy (5426111mg/gCr, 2496762 mg/gCr, 1856559 mg/gCr,, 1486449 mg/gCr as above, p!0.001). Serum cystatin C was increased with significance (1.30860.616 mg/dl, 1.44760.704 mg/dl, 1.50260.791 mg/dl, 1.60660.796 mg/dl as above, p ! 0.001). Biomarkers has different trends on the time course of the therapy of acute heart failure syndrome. Further investigations about pathophysiological meanings of these markers are required.
118 Repetitive Measurements of High Sensitive Cardiac Troponin I as a Prognostic Predictor in Stable Outpatients With Nonischemic Chronic Heart Failure MASANORI FUJII, TAKAYOSHI TSUTAMOTO, CHIHO KAWAHARA, MASAYUKI YAMAJI, KEIZOU NISHIYAMA, MINORU HORIE Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Shiga, Japan Background: Prognostic role of repetitive measurements of a high sensitive cardiac troponin I (hs-cTnI) in stable outpatients with CHF remain unknown. Methods: To evaluate the role of repetitive measurements of hs-cTnI (Centaur TnI-Ultra, Siemens, lower limit of detection50.006 ng/mL), in stable outpatients with nonischemic chronic heart failure (NICHF) (n5108), we performed echocardiography and measured plasma levels of cTnI and NT-proBNP at baseline and 4 months later and then prospectively followed-up for the 25 months. Results: Most patients received standard therapy (ACE-I/ARB; 95%, b-blockers; 83%, spironolactone; 85%). Thereafter, during a mean follow-up period of 18 months, 33 patients had cardiac events (death or rehospitalization). According to stepwise multivariate analyses, plasma Log NT-pro BNP after 4 months (p50.002), left ventricular ejection fraction after 4 months (p50.036), plasma hs-cTnI after 4 months (p50.004) and change of cTnI (4month-baseline) (p50.028) were independent significant predictors of cardiac events. Hazard ratio of patients with cTnI (after 4 months) O 0.04 ng/mL and change of cTnI O 0 was 23.0 (95% confidence interval, 3.0 -92.2) compared to that of those with cTnI ! 0.04 ng/mL and change of cTnI ! 0 for cardiac events (p!0.05).Conclusions: These results indicate that a recent absolute value of hs-cTnI and an increase in hs-cTnI are an independent prognostics predictor in stable outpatients with NICHF.
119 In failing hearts, the interaction of N-terminal (N: 0-600) and central domains (C: 20002500) of the cardiac ryanodine receptor (RyR2) has been shown to be defective (i.e. domain unzipping), rendering the channel leaky. Here, we investigated the pathogenic role of calmodulin (CaM), one of the accessory proteins in RyR2, in the leaky channel in heart failure (HF).Methods and results. Cardiomyocytes were isolated from dog LV muscles {normal; 4-weeks rapid RV pacing (HF) }. To assess CaM binding to RyR2, exogenous CaM labeled with Alexa FluorÒ was incorporated in saponin-permiabilized, isolated cardiomyocytes ([Ca2+]575 nM). The Alexa-CaM was specifically bound to the sub-cellular fraction, and the binding affinity of CaM was decreased in
AT1 Receptor Activated by Toll Like Receptor 4 in the Brainstem Causes Sympathoexcitation in Mice With Heart Failure KIYOHIRO OGAWA, YOSHITAKA HIROOKA, TAKUYA KISHI, KENJI SUNAGAWA The Department of Cardiovascular medicine, Kyushu University Graduate school of medical science, Fukuoka, Japan Background: Previous studies suggest that heart failure (HF) is associated with sympathoexcitation due to oxidative stress in the brain induced by AT1 receptor
The 14th Annual Scientific Meeting (AT1R). In the brain, oxidative stress is known as an upstream of inflammatory signaling pathway mediated by toll-like receptor 4 (TLR4). The aim of this study is to determine whether AT1R-induced sympathoexcitation is mediated by TLR4 in the brainstem of HF model or not. Method and Results: As a HF model, ligation of left coronary artery was performed to make large myocardial infarction (MI) and subsequent HF in ICR mice. On day 10 after left coronary artery ligation, mice received intracerebroventricular (ICV) injection of losartan (CHF-Los) or vehicle (CHF-Veh) by osmotic minipumps for 14 days. The expression of TLR4 in the brainstem determined by Western blot analysis was significantly higher in HF than in sham mice (1.05660.04 vs 0.5660.11, n55 for each, P!0.05) and was significantly lower in CHF-Los than in CHF-Veh (0.2960.04 vs 0.6560.05, n57 for each, P!0.05). Urinary norepinephrine excretion as a parameter of sympathetic nervous system activity was significantly lower in CHF-Los than in CHF-Veh (369.2626 pg/day vs 589650 pg/day, n53 for each, P!0.05) Conclusion: Sympathoexcitation and LV dysfunction in HF, caused by AT1 receptor in the brainstem, is mediated in part by TLR4.
120 Apparently Slight Ventricular Dysfunction Predisposes Obese Type 2 Diabetic Rats to High Mortality After Myocardial Infarction HIDEMICHI KOUZU, AKIFUMI TAKADA, TAKAYUKI MIKI, MASAYA TANNO, TOSHIYUKI YANO, ATSUSHI KUNO, TAKAHITO ITOH, TATSUYA SATOH, TETSUJI MIURA Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan Objective: We recently reported that up-regulated calcineurin disrupts cytoprotective signaling in type 2 diabetic rat hearts (OLETFs) (Circ Res 2010;106:129-32). Here we assessed alterations in ventricular function by type 2 diabetes and its impact on outcomes after myocardial infarction. Methods and Results: Left ventricular end-systolic elastance (Ees) and LV dP/dtmax were slightly lower (1.6860.10 vs. 1.9560.08 mmHg/ml and 58866413 vs. 78396560 mmHg/s, respectively) and t was larger (12.161.15 vs. 8.8760.96 msec) in OLETFs at ages between 25-30 weeks than those in LETOs, though LVEF was similar in the two groups (55.564.4 vs. 59.966.0%). Using separate groups of rats, myocardial infarction was induced by coronary artery ligation. Before ischemia, %FS and LVEF determined by echocardiography were similar in OLETFs and LETOs (41.762.2 vs. 43.461.2% and 77.562.3 vs. 79.661.3%). However, mortality 48 hrs after infarction was significantly higher in OLETFs than LETOs (58.4% vs. 7.7%), and telemetric recording of ECG and blood pressure indicated that rapid progression of heart failure was responsible for the higher mortality in OLETFs. Pretreatment with cyclosporine A (20 mg/kg for 7days) did not reduce mortality after infarction in OLETFs. Conclusion: Slight impairment of systolic and diastolic ventricular functions in diabetic hearts is associated with substantial increase in post-infarct mortality, which appears to be unrelated with up-regulated tissue calcineurin activity.
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122 Respiratory Stability in Patients With Chronic Heart Failure: A New Method to Define Optimal Respiratory Assist DAISUKE HARADA, JUNYA TAKAGAWA, HIROSHI UENO, HISANARI ISHISE, HIDETSUGU ASANOI Imizu City Hospital, Toyama, Japan Despite several kinds of positive airway pressure support, there have been no quantitative tools to define which ventilatory assist serves most in patients with heart failure. Heart failure is characterized by conditions of unstable and periodically fluctuated respiration both during daytime and during night. Recently, we have developed a new quantitative index to assess respiratory stability derived from a serial respiratory flow curve, the respiratory stability index (RSI). In patients with heart failure, we applied adaptive servo ventilator (ASV) and compared influences of sereveral positive end-expiratory pressure (PEEP) on respiratory stability. We measured serial changes in HR, high-frequency components of RR-interval variations, and the respiratory stability index. Heart rate variability rose initially and gradually declined along with the reduction in tidal volume with ASV. RSI varied with the level of positive end-expiratory pressure and indicated the opimal PEEP level of ASV in each patient. Thus, the respiratory stability provides a indicator to define optimal ventilatory assist in each patient with heart failure.
123 Effect of Adaptive Servo-Ventilation on Muscle Sympathetic Nerve Activity in Patients With Heart Failure and Renal Insufficiency DAISUKE HARADA1, SHUJI JOHO1, YOSHITAKA ODA1, TADAKAZU HIRAI1, HIDETSUGU ASANOI2, HIROSHI INOUE1 1 Second Department of Internal Medicine, Toyama University Hospital, Toyama, Japan, 2Imizu City Hospital, Toyama, Japan Background: Sympathetic nerve activity is overactivated in patients with heart failure (HF) complicated with renal insufficiency (RI). However, it is still unknown whether adaptive servo-ventilation (ASV) has sympathoinhibitory effect in patients with HF and RI. Here, we examined whether ASV exerts a sympathoinhibitory effect in patients with HF and RI. Methods: Sixteen patients with HF (stage C) were enrolled and divided into 2 groups: RI group (n58, estimated glomerular filtration rate !60 ml/min/1.73m2) or no RI group (n58). Muscle sympathetic nerve activity (MSNA), heart rate, blood pressure, and oxygen saturation level were monitored continuously before (10min) and during application of ASV (30min). Result: MSNA was higher in RI group than in no RI group at baseline (80 6 12 vs 54 6 19 burst/100beats, p!0.01). Although heart rate and blood pressure were unchanged during application of ASV, oxygen saturation level was increased similarly in both groups (both, p!0.01). Although MSNA was also decreased in both groups (both, p!0.01), the change of MSNA was significantly greater in RI group (-1566 burst/ 100beats) than in no RI group (-866 burst/100beats) (p!0.01). Conclusion: These findings suggest that ASV may have sympathoinhibitory effect especially in patients with HF and RI.
124 121 Serum Surfactant Protein D Reflects Pulmonary Congestion in Patients With Chronic Heart Failure SHUNSUKE NETSU, TETSURO SHISHIDO, TAKANORI ARIMOTO, HIROKI TAKAHASHI, TAKEHIKO MIYASHITA, TAKUYA MIYAMOTO, JOJI NITOBE, TETSU WATANABE, ISAO KUBOTA Department of Cardiology, Pulmonology, Nephrology, Yamagata University School of Medicine, Yamagata, Japan Background: Previous study have shown pulmonary edema causes alveolar-capillary barrier damage and leads to leakage of pulmonary surfactant protein B into the plasma. Surfactant protein D (SP-D) is useful biomarker for active interstitial pneumonia, however, the relationship to chronic heart failure (CHF) remained to be determined. Thus, we investigated whether serum SP-D reflects pulmonary congestion in patients with CHF. Methods and results: We measured SP-D in 100 patients with CHF and 25 control subjects, and examined the relationship between SP-D and cardiac catheterization measurements. Compared to control subjects, CHF patients had significantly higher SP-D value (41.5 6 22.9 vs 73.3 6 40.1 ng/ml, P!0.05). Furthermore, we found that SP-D was significantly correlated with mean pulmonary capillary wedge pressure (R50.32, P50.0038) and right ventricular systolic pressure (R50.38, P!0.0001). However, SP-D had no significant correlation with parameters of left ventricular function and very weak correlation with plasma brain natreuretic peptide level (R50.178, P!0.05). Conclusion: High levels of SP-D reflect pulmonary congestion and is an useful biomarker for right heart load in patients with CHF.
Chronotropic Inconpetence After Implantation of Pacemaker for Complete A-V Block MIE SEYA1, MAKOTO SUZUKI1, TOMOFUMI NAKAMURA1, MASAHIKO SETOGUTI1, WATARU NAGAHORI1, MASAKAZU OONO1, AKIIHIKO MATSUMURA1, YUJI HASHIMOTO1, MITSUAKI ISOBE2 1 Kameda medical center, 2Tokyo Medical and Dental University, Department of Cardiology Background: Addition of rate response function in pacemakers has generally been considered unnecessary in patient with complete atrial ventriculer block (CAVB), because the sinus node function is normal. However, there have been reports of cases in which chronotropic incompetence appeared after pacemaker implantation. As it is now, pacemakers are checked but they are not adjusted according to the patients level of activity. In our study, we followed patients to determine the frequency of chronotropic incompetence. Methods: We defined chronotropic incompetence as patients with over 50% atrial pacing. 147 patients who underwent a DDD/DDI pacemaker implantation for CAVB were followed for poor heart rate response.Results: Of the 147 patients, poor HR response was seen in 33 patients(22.4%). The mean follow-up period after implantation was 64.3 months. Of the 33 patients with poor HR response, 11 patients(33.3%) had a rate response function added. Of 11 patients, 9 patients(81.8%) had rate response function from the time of implantation. 22 patients(66.6%) who had a poor HR response did not have a rate response function added. Conclusion: HR response according to the level of exercise is considered important to maintain QOL. However, as it many patients do not have a rate response function added and this should be taken into consideration at the time of regular pacemaker check.
114 Cardiac Resynchronaization Therapy Enables to Reinforce Medication With Beta-Blocker and ACE-I, and Reduse a Risk of Rehospitalization SHINSUKE IWAI1, JUNICHI NITTA1, KENSUKE IHARA1, MITSUTOSHI ASANO1, AKIRA SATO1, TSUNEHIRO YAMATO1, YUTAKA MATSUMURA1, KAZUYASU TAKEI1, KIHIRO ASAKAWA1, MITSUAKI ISOBE2 1 Cardiovascular Medicine, Saitama Red Cross Hospital, Saitama, Japan, 2Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan The first case, a 71-year-old man complained of dyspnea, and repeated rehospitalization due to congestive heart failure by dialated cardiomyopathy. It was difficult to taper catecholamine. Electrocardiogram on admission showed CLBBB with wide QRS, and echocardiography showed diffuse hypokinetic left ventricular wall motion(ejection fraction 27%)with interventricular dyssynchrony. After implantation of CRT-D, we successed to taper catecholamine, introduce ACE-I(Perindopril 4mg/day), and increase dose of beta-blocker(Carvedilol 5mg to 20mg/day) while decrease diuretics. Hyponatremia was improved by decreasing diuretics. For a follow up period, he was not need to be admitted to hospital. BNP levels decreased from 1356 to 566 pg/ml. The second case, a 81-year-old man with congestive heart failure by dialated cardiomyopathy, who repeated rehospitalization and it was difficult to get out of the hospital. Electrocardiogram showed CLBBB with wide QRS, and echocardiography showed diffuse hypokinetic left ventricular wall motion with interventricular dyssynchrony. After implantation of CRT-D, we successed to taper catecholamine, introduce ACE-I(Perindopril 2mg/day), and increase dose of beta-blocker(Carvedilol 7.5mg to 10mg/day). For a follow up period, he was admitted to a hospital twice but we could reduce hospital time and prolong intervals to hospitalization. We report two cases that Cardiac resynchronaization therapy enabled to reinforce medication with betablocker and ACE-I, and reduse a risk of rehospitalization and hospital time.
115 A Case of Restoration of Cardiac Function Within a Few Months Treated as DCM for More than 8 Years TORU OGAWA, YASUHIRO SATOH, RYUICHI KATO, MASAHIRO SEKIGAWA, MASAAKI SHOJI, YUJI KONISHI, JUNKO ITO, KAORU SAKURAI, YASUHIRO YOKOYAMA, TAKASHI ASHIKAGA The Department of Cardiology, National Hospital Organization Disaster Medical Center, Tokyo, Japan Forty-two years old male complained of exertional dyspnea and was admitted into our ward. His past history was hypertension, diabetes mellitus at 34 years old. At that point poor LV function was pointed out and catheterization study was done. No coronary lesion was revealed with severely impaired LV wall motion. He was diagnosed as dilated cardiomyopathy, although not typical, and he was treated by digitalis, beta blockade and ARB in the outpatient clinic since then. He was readmitted due to the above symptom on December 2009. Two weeks prior to admission, he had fever and cough treated by antibiotics. Transthoracic echocardiography showed balllike mobile thrombus (402017mm) in LV. LV ejection fraction was 36% and BNP was 1100 pg/ml. Heparin administration followed by warfarinization was started and finally thrombus disappeared without complication. Together with thrombus resolution (2010 February) LV function restored from 36% to 62%. BNP level returned to normal (11.1). Conclusion: LV function in DCM was not supposed to restore especially in a short period. Since this patient suffered from infection before the worsening of cardiac symptom, infection of myocardial involvement might play an important role on the mechanism of LV function reversibility.
116 Defective Calmodulin Binding to RyR2 Renders the Ca2+ Release Channel Leaky in Failing Hearts AKIHIRO HINO, MASAFUMI YANO, TAKESHI SUETOMI, MAKOTO ONO, XIAOJUAN XU, HITOSHI UCHINOUMI, MASAHIRO DOI, SHINICHI OKUDA, SHIGEKI KOBAYASHI, TAKESHI YAMAMOTO Yamaguchi Univ Graduate Sch of Med, Ube, Japan
failing cells. Addition of DPc10 (10 mM), which was found to induce domain unzipping mimicking failing SR, to normal cells decreased the CaM binding. Conversely, the decreased CaM binding seen in failing cells was attenuated by addition of dantrolene (Dan), which was found to correct the defective N-C inter-domain interaction (i.e. domain unzipping to zipping). In saponin-permeabilized, failing cells, the frequency of Ca2+ sparks was markedly increased, whereas addition of either Dan or high concentration of CaM (1mM) inhibited the increase in SpF. Conclusions. The defective interdomain interaction between N-C domains within RyR2 reduces the CaM binding affinity to RyR2, subsequently increasing spontaneous Ca2+ release events in failing SR.
117 Biomarkers About Cardio-Renal Continuum, Serum CystatinC and Urine Micro Albumin Vary on the Course of Treatment Acute Heart Failure Syndrome SATOSHI KOYAMA1, YUKIHITO SATO1, MANA KAWASHIMA1, TAKUMA SAWA1, YOHEI TANADA1, ERIKA YAMAMOTO1, SAYAKA SAIJO1, TAKAKO FUJIWARA2, YOSHIKI TAKATSU1, HISAYOSHI FUJIWARA1 1 Department of cardiology, Hyogo prefectural Amagasaki Hospital, Amagasaki, Japan, 2Kyoto Women‘s university There are many reports about the effectiveness of cardiac biomarkers in the treatment of acute heart failure. We assessed urine micro albumin and serum cystatin C of the patients who required admission due to acute heart failure syndrome(n542) as a biomarkers of Cardio-renal Continuum. Blood and urine samples were collected from these patients on the admission day, 4th, 7th and 14th day after the admission. We assessed NT-pro BNP and Cardiac Troponin-T concurrently as biomarkers about cardiac failure. Patients were treated with vasodilator (nitroglycerin or hANP) with or without diuretics and inotropic agent at a physician‘s discretion.NT-pro BNP was decreased rapidly in response to the therapy(10014618497ng/ml, 525469704 ng/ml, 4893610726 ng/ml, 4381611028 ng/ml, admission day, the 4th,7th,14th day after admission respectively, p50.002), however Troponin T had a tendency for increase(0.03660.005 ng/ml, 0.03560.005 ng/ml, 0.03460.005 ng/ml, 0.03960.008 ng/ml as above, p50.50). Urine micro albumin significantly decreased in response to the therapy (5426111mg/gCr, 2496762 mg/gCr, 1856559 mg/gCr,, 1486449 mg/gCr as above, p!0.001). Serum cystatin C was increased with significance (1.30860.616 mg/dl, 1.44760.704 mg/dl, 1.50260.791 mg/dl, 1.60660.796 mg/dl as above, p ! 0.001). Biomarkers has different trends on the time course of the therapy of acute heart failure syndrome. Further investigations about pathophysiological meanings of these markers are required.
118 Repetitive Measurements of High Sensitive Cardiac Troponin I as a Prognostic Predictor in Stable Outpatients With Nonischemic Chronic Heart Failure MASANORI FUJII, TAKAYOSHI TSUTAMOTO, CHIHO KAWAHARA, MASAYUKI YAMAJI, KEIZOU NISHIYAMA, MINORU HORIE Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Shiga, Japan Background: Prognostic role of repetitive measurements of a high sensitive cardiac troponin I (hs-cTnI) in stable outpatients with CHF remain unknown. Methods: To evaluate the role of repetitive measurements of hs-cTnI (Centaur TnI-Ultra, Siemens, lower limit of detection50.006 ng/mL), in stable outpatients with nonischemic chronic heart failure (NICHF) (n5108), we performed echocardiography and measured plasma levels of cTnI and NT-proBNP at baseline and 4 months later and then prospectively followed-up for the 25 months. Results: Most patients received standard therapy (ACE-I/ARB; 95%, b-blockers; 83%, spironolactone; 85%). Thereafter, during a mean follow-up period of 18 months, 33 patients had cardiac events (death or rehospitalization). According to stepwise multivariate analyses, plasma Log NT-pro BNP after 4 months (p50.002), left ventricular ejection fraction after 4 months (p50.036), plasma hs-cTnI after 4 months (p50.004) and change of cTnI (4month-baseline) (p50.028) were independent significant predictors of cardiac events. Hazard ratio of patients with cTnI (after 4 months) O 0.04 ng/mL and change of cTnI O 0 was 23.0 (95% confidence interval, 3.0 -92.2) compared to that of those with cTnI ! 0.04 ng/mL and change of cTnI ! 0 for cardiac events (p!0.05).Conclusions: These results indicate that a recent absolute value of hs-cTnI and an increase in hs-cTnI are an independent prognostics predictor in stable outpatients with NICHF.
119 In failing hearts, the interaction of N-terminal (N: 0-600) and central domains (C: 20002500) of the cardiac ryanodine receptor (RyR2) has been shown to be defective (i.e. domain unzipping), rendering the channel leaky. Here, we investigated the pathogenic role of calmodulin (CaM), one of the accessory proteins in RyR2, in the leaky channel in heart failure (HF).Methods and results. Cardiomyocytes were isolated from dog LV muscles {normal; 4-weeks rapid RV pacing (HF) }. To assess CaM binding to RyR2, exogenous CaM labeled with Alexa FluorÒ was incorporated in saponin-permiabilized, isolated cardiomyocytes ([Ca2+]575 nM). The Alexa-CaM was specifically bound to the sub-cellular fraction, and the binding affinity of CaM was decreased in
AT1 Receptor Activated by Toll Like Receptor 4 in the Brainstem Causes Sympathoexcitation in Mice With Heart Failure KIYOHIRO OGAWA, YOSHITAKA HIROOKA, TAKUYA KISHI, KENJI SUNAGAWA The Department of Cardiovascular medicine, Kyushu University Graduate school of medical science, Fukuoka, Japan Background: Previous studies suggest that heart failure (HF) is associated with sympathoexcitation due to oxidative stress in the brain induced by AT1 receptor
The 14th Annual Scientific Meeting (AT1R). In the brain, oxidative stress is known as an upstream of inflammatory signaling pathway mediated by toll-like receptor 4 (TLR4). The aim of this study is to determine whether AT1R-induced sympathoexcitation is mediated by TLR4 in the brainstem of HF model or not. Method and Results: As a HF model, ligation of left coronary artery was performed to make large myocardial infarction (MI) and subsequent HF in ICR mice. On day 10 after left coronary artery ligation, mice received intracerebroventricular (ICV) injection of losartan (CHF-Los) or vehicle (CHF-Veh) by osmotic minipumps for 14 days. The expression of TLR4 in the brainstem determined by Western blot analysis was significantly higher in HF than in sham mice (1.05660.04 vs 0.5660.11, n55 for each, P!0.05) and was significantly lower in CHF-Los than in CHF-Veh (0.2960.04 vs 0.6560.05, n57 for each, P!0.05). Urinary norepinephrine excretion as a parameter of sympathetic nervous system activity was significantly lower in CHF-Los than in CHF-Veh (369.2626 pg/day vs 589650 pg/day, n53 for each, P!0.05) Conclusion: Sympathoexcitation and LV dysfunction in HF, caused by AT1 receptor in the brainstem, is mediated in part by TLR4.
120 Apparently Slight Ventricular Dysfunction Predisposes Obese Type 2 Diabetic Rats to High Mortality After Myocardial Infarction HIDEMICHI KOUZU, AKIFUMI TAKADA, TAKAYUKI MIKI, MASAYA TANNO, TOSHIYUKI YANO, ATSUSHI KUNO, TAKAHITO ITOH, TATSUYA SATOH, TETSUJI MIURA Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan Objective: We recently reported that up-regulated calcineurin disrupts cytoprotective signaling in type 2 diabetic rat hearts (OLETFs) (Circ Res 2010;106:129-32). Here we assessed alterations in ventricular function by type 2 diabetes and its impact on outcomes after myocardial infarction. Methods and Results: Left ventricular end-systolic elastance (Ees) and LV dP/dtmax were slightly lower (1.6860.10 vs. 1.9560.08 mmHg/ml and 58866413 vs. 78396560 mmHg/s, respectively) and t was larger (12.161.15 vs. 8.8760.96 msec) in OLETFs at ages between 25-30 weeks than those in LETOs, though LVEF was similar in the two groups (55.564.4 vs. 59.966.0%). Using separate groups of rats, myocardial infarction was induced by coronary artery ligation. Before ischemia, %FS and LVEF determined by echocardiography were similar in OLETFs and LETOs (41.762.2 vs. 43.461.2% and 77.562.3 vs. 79.661.3%). However, mortality 48 hrs after infarction was significantly higher in OLETFs than LETOs (58.4% vs. 7.7%), and telemetric recording of ECG and blood pressure indicated that rapid progression of heart failure was responsible for the higher mortality in OLETFs. Pretreatment with cyclosporine A (20 mg/kg for 7days) did not reduce mortality after infarction in OLETFs. Conclusion: Slight impairment of systolic and diastolic ventricular functions in diabetic hearts is associated with substantial increase in post-infarct mortality, which appears to be unrelated with up-regulated tissue calcineurin activity.
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122 Respiratory Stability in Patients With Chronic Heart Failure: A New Method to Define Optimal Respiratory Assist DAISUKE HARADA, JUNYA TAKAGAWA, HIROSHI UENO, HISANARI ISHISE, HIDETSUGU ASANOI Imizu City Hospital, Toyama, Japan Despite several kinds of positive airway pressure support, there have been no quantitative tools to define which ventilatory assist serves most in patients with heart failure. Heart failure is characterized by conditions of unstable and periodically fluctuated respiration both during daytime and during night. Recently, we have developed a new quantitative index to assess respiratory stability derived from a serial respiratory flow curve, the respiratory stability index (RSI). In patients with heart failure, we applied adaptive servo ventilator (ASV) and compared influences of sereveral positive end-expiratory pressure (PEEP) on respiratory stability. We measured serial changes in HR, high-frequency components of RR-interval variations, and the respiratory stability index. Heart rate variability rose initially and gradually declined along with the reduction in tidal volume with ASV. RSI varied with the level of positive end-expiratory pressure and indicated the opimal PEEP level of ASV in each patient. Thus, the respiratory stability provides a indicator to define optimal ventilatory assist in each patient with heart failure.
123 Effect of Adaptive Servo-Ventilation on Muscle Sympathetic Nerve Activity in Patients With Heart Failure and Renal Insufficiency DAISUKE HARADA1, SHUJI JOHO1, YOSHITAKA ODA1, TADAKAZU HIRAI1, HIDETSUGU ASANOI2, HIROSHI INOUE1 1 Second Department of Internal Medicine, Toyama University Hospital, Toyama, Japan, 2Imizu City Hospital, Toyama, Japan Background: Sympathetic nerve activity is overactivated in patients with heart failure (HF) complicated with renal insufficiency (RI). However, it is still unknown whether adaptive servo-ventilation (ASV) has sympathoinhibitory effect in patients with HF and RI. Here, we examined whether ASV exerts a sympathoinhibitory effect in patients with HF and RI. Methods: Sixteen patients with HF (stage C) were enrolled and divided into 2 groups: RI group (n58, estimated glomerular filtration rate !60 ml/min/1.73m2) or no RI group (n58). Muscle sympathetic nerve activity (MSNA), heart rate, blood pressure, and oxygen saturation level were monitored continuously before (10min) and during application of ASV (30min). Result: MSNA was higher in RI group than in no RI group at baseline (80 6 12 vs 54 6 19 burst/100beats, p!0.01). Although heart rate and blood pressure were unchanged during application of ASV, oxygen saturation level was increased similarly in both groups (both, p!0.01). Although MSNA was also decreased in both groups (both, p!0.01), the change of MSNA was significantly greater in RI group (-1566 burst/ 100beats) than in no RI group (-866 burst/100beats) (p!0.01). Conclusion: These findings suggest that ASV may have sympathoinhibitory effect especially in patients with HF and RI.
124 121 Serum Surfactant Protein D Reflects Pulmonary Congestion in Patients With Chronic Heart Failure SHUNSUKE NETSU, TETSURO SHISHIDO, TAKANORI ARIMOTO, HIROKI TAKAHASHI, TAKEHIKO MIYASHITA, TAKUYA MIYAMOTO, JOJI NITOBE, TETSU WATANABE, ISAO KUBOTA Department of Cardiology, Pulmonology, Nephrology, Yamagata University School of Medicine, Yamagata, Japan Background: Previous study have shown pulmonary edema causes alveolar-capillary barrier damage and leads to leakage of pulmonary surfactant protein B into the plasma. Surfactant protein D (SP-D) is useful biomarker for active interstitial pneumonia, however, the relationship to chronic heart failure (CHF) remained to be determined. Thus, we investigated whether serum SP-D reflects pulmonary congestion in patients with CHF. Methods and results: We measured SP-D in 100 patients with CHF and 25 control subjects, and examined the relationship between SP-D and cardiac catheterization measurements. Compared to control subjects, CHF patients had significantly higher SP-D value (41.5 6 22.9 vs 73.3 6 40.1 ng/ml, P!0.05). Furthermore, we found that SP-D was significantly correlated with mean pulmonary capillary wedge pressure (R50.32, P50.0038) and right ventricular systolic pressure (R50.38, P!0.0001). However, SP-D had no significant correlation with parameters of left ventricular function and very weak correlation with plasma brain natreuretic peptide level (R50.178, P!0.05). Conclusion: High levels of SP-D reflect pulmonary congestion and is an useful biomarker for right heart load in patients with CHF.
Chronotropic Inconpetence After Implantation of Pacemaker for Complete A-V Block MIE SEYA1, MAKOTO SUZUKI1, TOMOFUMI NAKAMURA1, MASAHIKO SETOGUTI1, WATARU NAGAHORI1, MASAKAZU OONO1, AKIIHIKO MATSUMURA1, YUJI HASHIMOTO1, MITSUAKI ISOBE2 1 Kameda medical center, 2Tokyo Medical and Dental University, Department of Cardiology Background: Addition of rate response function in pacemakers has generally been considered unnecessary in patient with complete atrial ventriculer block (CAVB), because the sinus node function is normal. However, there have been reports of cases in which chronotropic incompetence appeared after pacemaker implantation. As it is now, pacemakers are checked but they are not adjusted according to the patients level of activity. In our study, we followed patients to determine the frequency of chronotropic incompetence. Methods: We defined chronotropic incompetence as patients with over 50% atrial pacing. 147 patients who underwent a DDD/DDI pacemaker implantation for CAVB were followed for poor heart rate response.Results: Of the 147 patients, poor HR response was seen in 33 patients(22.4%). The mean follow-up period after implantation was 64.3 months. Of the 33 patients with poor HR response, 11 patients(33.3%) had a rate response function added. Of 11 patients, 9 patients(81.8%) had rate response function from the time of implantation. 22 patients(66.6%) who had a poor HR response did not have a rate response function added. Conclusion: HR response according to the level of exercise is considered important to maintain QOL. However, as it many patients do not have a rate response function added and this should be taken into consideration at the time of regular pacemaker check.