High Serum Level of Pregnancy Associated Plasma Protein A (PAPP-A) is a Risk Factor of Patients With Heart Failure

High Serum Level of Pregnancy Associated Plasma Protein A (PAPP-A) is a Risk Factor of Patients With Heart Failure

S174 Journal of Cardiac Failure Vol. 15 No. 7S September 2009 Therefore, IABP was inserted from left femoral artery, and emergent adrenalectomy was pe...

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S174 Journal of Cardiac Failure Vol. 15 No. 7S September 2009 Therefore, IABP was inserted from left femoral artery, and emergent adrenalectomy was performed without any complication. After adrenalectomy, his hemodynamic condition gradually improved because of a long-term treatment with IABP for 2 months and optimal medication including beta-blocker and angiotensin-converting enzyme (ACE) inhibitor. He was discharged from hospital 6 months after adrenalectomy without any recurrence of pheochromocytoma. Echocardiographic images 12 months later revealed improvement in LV ejection fraction (40%), and BNP levels have normalized.

103 The Prognostic Importance of Serum Sodium Concentration and Electrocardiographic QRS Duration in Patients Planned for Cardiac Resynchronization Therapy KENSHIRO ARAO1, TAISHI HIRAHARA2, YOSHITAKA SUGAWARA1, CHIKASHI SUGA2, NORIFUMI KUBO2, MASANOBU KAWAKAMI1,2, SHINICHI MOMOMURA2 1 First department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Japan, 2Department of Cardiovascular Medicine, Saitama Medical Center,Jichi Medical University, Japan Background: Hyponatremia or wide QRS duration in heart failure (HF) patients associates with poor clinical outcome respectively. Conversely, HF patients with wide QRS tended to be responsive to cardiac resynchronization therapy (CRT). We explore associations among them and their influences on clinical outcome after CRT implantation. Methods: We enrolled 35 HF patients (M/F 21/14, 63 6 12 years old) planned for CRT. Baseline QRS duration on ECG, serum sodium (Na) concentration were measured. All the patients were divided into four groups according to baseline median Na concentration and QRS duration: high Na narrow QRS (HN, n 5 9), high Na wide QRS (HW, n 5 9), low Na narrow QRS (LN, n 5 8) and low Na wide QRS (LW, n 5 9), and were followed about major adverse cardiac events (MACEs) after CRT implantation. MACEs included unexpected HF hospitalization, taking heart transplantation and cardiac death. Results: At baseline, there were no differences in age, EF, BNP, LV diameter among four groups. Ten of 35 CRT recipients had MACEs during following up periods (median:320, range: 36-1111 days, unexpected HF hospitalization:1, heart transplantation:1, cardiac death:1). LW had high incidence of MACEs after CRT implantation among four groups (Figure, p 5 0.0039). Conclusions: In the condition of hyponatremia, patients with wider QRS duration might have a poor prognosis even after CRT implantation.

104 Effects of Low-dose Telmisartan (TEL) in Mice With Heart Failure (HF) Complicated by Chronic Kidney Disease (CKD) TAKAHIRO INOUE1, TOMOMI IDE1, KIICHIRO FUJISAKI2, ATSUSHI TANAKA1, KAZUHIKO TSURUYA2, YUKO HATA1, KENJI SUNAGAWA1 1 Department of Cardiovascular Medicine, Kyushu University, Fukuoka, JAPAN, 2 Department of Internal Mdicine, Kyushu University, Fukuoka, JAPAN Background: The aims of this study are to establish a CKD-HF model and to examine the contributions of angiotensin II on cardio-renal syndrome using low-dose TEL. Methods: CKD were created by 5/6 nephrectomy. For CKD-HF model, we created myocardial infarction (MI) on the CKD mice. TEL was orally-administered from day 26 after nephrectomy. Results: CKD-HF increased non-infarcted LV weight, LV enddiastolic pressure, collagen fraction volume and myocardial hypertrophy. Moreover, CKD synergistically increased mortality in HF. Administration of TEL improved ventricular function (Table) in CKD-HF and markedly improved survival. Conclusion: Despite little changes in LV systolic function or systemic hemodynamics, CKD deteriorated LV diastolic function and decreased survival after MI. The fact

that TEL markedly benefits CKD-HF suggests that angiotensin II plays a pivotal role in worsening HF with CKD.

105 Comparison of the Development to End-Stage Phase in Hypertrophic Cardiomyopathy With Thick Filament Mutations and Thin Filament Mutations NOBORU FUJINO, HIDEKAZU INO, EIICHI MASUTA, AKIRA FUNADA, AKIHIKO MURAMOTO, JUNICHIRO YOKAWA, MASAKAZU YAMAGISHI Division of Cardiovascular Medicine, Kanazawa University, Kanazawa, Japan Background: Hypertrophic cardiomyopathy (HCM) is a disease of sarcomere and approximately 5% of cases develop to end-stage phase with decreased left ventricular contractility. However, few data exist regarding the differences in clinical course to end-stage HCM among carriers with different gene mutations. Therefore, we compared the clinical course to end-stage HCM between mutation carriers with thick-filament gene (MYH7 and MYBPC3: Group-Thick) and those with thin-filament gene (TNNT2 and TNNI3: Group-thin). Methods and Results: The study comprised of 146 HCM patients with sarcomere gene mutations that were determined by PCRSSCP or direct sequence. We compared echocardiographic parameters and cardiac event defined by the development to end-stage phase (%fractional shortening: FS ! 25%). There were 71 HCM patients in Group-Thick (mean age 53.9) and 75 in Group-thin (44.8, P ! 0.05). No differences were found in interventricular septal wall thickness (16.4 mm vs.14.8 mm), left ventricular end-diastolic dimension (45.0 mm vs. 44.5 mm), and FS (28.3% vs. 29.3%), respectively, between GroupThick and Group-thin. Interestingly, the age developing to end-stage phase was lower in Group-thin than in Group-Thick (Kaplan-Meier, Log rank, P ! 0.05). Conclusions: These results demonstrate the differences in age developing to endstage phase in HCM with different mutations. We suggest performing earlier medical intervention such as beta-blockers in HCM with thin-filament gene mutations.

106 Follow-up of Two Cases With Dilated Cardiomyopathy Treated With Immunoadsorption YOSHIKAZU YAZAKI1, MITSUAKI HORIGOME1, HIROKI KASAI2, UICHI IKEDA2 1 Division of Cardiology, NHO Matsumoto Medical Center Matsumoto Hospital, Matsumoto, Japan, 2Department of Cardiovascular Medicine, Shinshu University School of Medicine, Matsumoto, Japan We report 2 cases of dilated cardiomyopathy treated with immunoadsorption (IA). IA was performed on three times (once a week) using an absorber (Immusorba TR350, Asahi Medical). The first case was a 63-year-old man diagnosed as having DCM in 1999. Before IA, echocardiography revealed restrictive physiology with a left ventricular ejection fraction (LVEF) of 21%, and right heart catheterization documented severely reduced cardiac index (CI:1.98l/min/m2) and increased pulmonary capillary wedge pressure (PCWP:26mmHg). The second case was a 76-year-old man diagnosed as having DCM in 1996. Before IA, echocardiography revealed restrictive physiology with a LVEF of 18%, and right heart catheterization documented severely reduced CI (1.58 l/min/m2) and increased PCWP (30mmHg). Acute hemodynamic effect was not seen before and just after IA in both cases. In the first case, there were marked improvements in echocardiographic variables (E/A: 4.63 to 0.83, E/ e’: 31.0 to 15.3, LVEF: 21 to 32%), hemodynamics (CI: 1.98 to 2.85 l/min/m2, PCWP: 26 to 10mmHg) and B-type natriuretic peptide (3170 to 247 pg/mL) during 1-year follow-up. In contrast, the second case did not have any clinical improvement by 3 months. These case experiences suggest that IA may be helpful therapeutic option for end-stage dilated cardiomyopathy, but appropriate selection of effective patients remained to be established.

107 High Serum Level of Pregnancy Associated Plasma Protein A (PAPP-A) is a Risk Factor of Patients With Heart Failure AKIRA FUNAYAMA, TETSURO SHISHIDO, TOSHIKI SASAKI, SHIGEHIKO KATOU, MITSUNORI ISHINO, SHUNSUKE NETSU, ISAO KUBOTA Department of Cardiology, Pulmonology,and Nephrology, Yamagata University School of Medicine, Yamagata, Japan Background: PAPP-A has insulin-like growth factor (IGF) binding protein-4 protease activity,which is associated with IGF bioactivity and involved in cardiac development and LV remodeling. It has been reported that PAPP-A correlates with various pathophysiologies; progression of atherosclerosis and coronary artery disease. However the clinical significance of serum PAPP-A in CHF has not been examined. The

The 13th Annual Scientific Meeting aim of this study was to determine the clinical significance of PAPP-A in patients with CHF. Methods and Results: Serum PAPP-A levels were measured in 182 patients and 20 control subjects. Serum PAPP-A levels were higher in patients with CHF than in control subjects and increased with advancing NYHA class. There were 53 cardiac events during a mean follow-up period of 796 6 698 days. Serum PAPP-A levels were higher in patients with cardiac events than in event-free patients.The multivariate Cox proportional hazard analysis demonstrated that serum PAPPA levels were the independent predictor of cardiac events (hazard ratio 1.676,95% CI 1.233-2.277, p ! 0.001).Patients were divided into 4 groups on the basis of PAPP-A level. The highest fourth quartile of serum PAPP-A levels were associated with the highest risk of cardiac events (5.63 fold compared with the first quartile). Conclusion: Serum PAPP-A level was related to the severity of CHF and associated with a high risk for adverse cardiac events.

108 The Predictive Variables of 6 Minute Walking Distance During Hospitalization in Patients With Chronic Heart Failure YUJI KONO1, SUMIO YAMADA2, YUKO SHIMIZU1, HISAKO OKUMURA1, FUMIHIKO MIYAKE3, TORU IZUMI4, COLLABORATIVE GROUP PTMATCH5 1 Program in Physical therapy, Nagoya University Graduate school of medicine, Nagoya, Japan, 2Nagoya University, School of Health Sciences, Nagoya, Japan, 3 Division of Cardiology, St, Marianna University School Medicine, Kawasaki, Japan, 4Department of Cardio-angiology, Kitasato University School of Medicine, Sagamihara, Japan, 5PTMaTCH collaborative group Objective: This study aimed to investigate the predictive variables of 6 minute walking distance (6MD) in patient with chronic heart failure (CHF) during hospitalized phase. Materials and Methods: The sample included 213 CHF subjects from the rehabilitation cohort study, Preventive effect of exercise for management of daily functioning in patients with chronic heart failure (PTMaTCH). First, the patients were divided into two subgroups according to the median value of the 6MD at the time of discharge, and the association of clinical variables during hospitalization, disease severity, physical function and the process of patient’s status, and the 6MD was analyzed. Then we performed logistic regression models to select the predictive variables to the 6MD. Results: The median score of 6MD was 350 m and almost same value as prognostic predict value (340 m) of previous report. Among a set of variables, the day for mobilization (OR: 0.80, P ! 0.001), grip strength (OR: 1.086, P 5 0.001), and leg extension strength (OR: 1.004, P 5 0.016) were selected for significant independent predictors of 6MD O 350 m. Conclusion: Our data indicate that not only physical function but the mobilization day were the predictor of 6MD O 350 m at time of discharge in CHF patients.

109 In Vivo RNA Interference of Protein Phosphatase 1 Beta Augments Cardiac Contracitility in Mice YOSUKE MIYAZAKI1, YASUHIRO IKEDA1, HIDEKAZU AOYAMA1, KOICHI YOSHIMURA2, MASAFUMI YANO1, MASUNORI MATSUZAKI1 1 Yamaguchi University School of Medicine, Department of Medicine and Clinical Science, Ube, Japan, 2Yamaguchi University School of Medicine, Department of Surgery and Clinical Science, Ube, Japan Background: Protein phosphatase 1 (PP1) is the negative regulator of cardiac contractility and known to be upregulated in the failing heart. PP1 consists of three different genes, namely PPP1CA(PP1a), PPP1CB(PP1b), and PPP1CC(PP1g). We previously reported that PP1b most significantly affect sarcoplasmic reticulum(SR)-mediated Ca2þ cycling in cultured cardiomyocytes. Herein we investigated whether in vivo knockdown of PP1b can augment Ca2þ cycling and cardiac contractility in normal mice. Methods: Adenoviral RNA polymerase II and micro RNA sequence mediated RNAi technique accompanying with Emerald (Em) GFP expression was employed to induce either knockdown of PP1b (AdV-CMV-EmGFP-PP1b-i) or delivery of control EmGFP-miR vector. Adenovirus was directly injected into the left ventricle(LV)(3 sites, 20 ml of 1011 vp/ml per site). Cardiac contractility was evaluated by echocardiography before and 7 days after adenoviral delivery, followed by biochemical and histological analyses. Results: Transfection efficiency was approximately 30% of the LV cross-sectional area as estimated by EmGFP fluorescence. PP1b expression was decreased by 36.3 6 0.7% (P ! 0.05, vs negative control) in immmunoblot analysis. PP1b-knockdown significantly improved % fractional shortening (PP1b-i vs. control: 49% vs. 42%, n 5 14 in each group, P ! 0.05) at 7th day after gene transfer. In phosphrylation assay, phosphorylation of Ser16-Phospholamban(PLN) was increased in PP1b knockdown group. Conclusion: Successful in vivo knockdown of PP1b by using adenoviral mi-RNA technology augmented cardiac contractility in normal mice.



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110 Serial Measurements of High-Sensitive Cardiac Troponin I and NT-proBNP in a Patient With Cardiac Sarcoidosis TAKUMA SAWA1, YUKIHITO SATO1, TADASHI MIYAMOTO1, SAYAKA SAIJO1, KIYOTO NISHI1, ERIKA YAMAMOTO1, YOHEI TANADA1, TAKAKO FUJIWARA2, HISAYOSHI FUJIWARA1, YOSHIKI TAKATSU1 1 Department of Cardiology, Hyogo Prefectural Amagasaki Hospital, Hyogo, Japan, 2 Department of food and nutrition, Kyoto women’s University, Kyoto, Japan A 68-year-old female with a history of ocular and pulmonary sarcoidosis was diagnosed as cardiac sarcoidosis with myocardial biopsy from her right ventricle. She once experienced sudden loss of consciousness, and frequent multifocal premature ventricular contraction and nonsustained ventricular tachycardia were seen in electrocardiogram. Delay enhancement (15 minutes after the gadolinium injection) in her cardiac MRI was 27% and lateral wall was strongly enhanced. Perfusion defect was seen at inferior wall and severe hypoperfusion at lateral wall in 99mTc-Tetrofosmin myocardial scintigram. She was treated with a daily dose of 1000 mg mPSL for 2days and switched to 30 mg PSL from day3, then tapered down to 25 mg PSL from day 39. Ejection fraction, left ventricle dimension in diastolic phase, left atrial dimension, and E/S’ were 0.43, 45 mm, 37 mm, 18.2 in echocardiogram at baseline, and improved to 0.57, 39 mm, 35 mm, 14.3 respectively at day 53, which indicates both systolic and diastolic functions were reformed. The efficacy of the treatment was also monitored by the level of NT-proBNP and high-sensitive cTnI (defined as a measurement exceeding the 99th percentile of a reference control group). Concentrations of NT-proBNP were 2345 pg/ml at baseline, 2438 pg/ml at day7, 1444 pg/ml at day42, and cTnI were 0.319ng/ml, 0.041ng/ml, and 0.028ng/ ml respectively. In conclusion, both NT-proBNP and cTnI might be used as therapeutic markers in patients with cardiac sarcoidosis.

111 The Effects of Endovascular Stent Graft on Vascular Function and Cardiac Structure Within a Very Short Term YASUHARU TAKEDA1, YASUSHI SAKATA1, TOSHIAKI MANO1, DAISUKE KAMIMURA1, SYUNSUKE TAMAKI1,2, YOSUKE OMORI1, YASUMASA TSUKAMOTO1, YOSHIHIRO AIZAWA1, KAZUHIRO YAMAMOTO1,2, ISSEI KOMURO1 1 Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan, 2The Center for Advanced Medical Engineering and Informatics, Osaka University, Suita, Japan Background: The endovascular stent graft is used in the growing number of patients with thoracic or abdominal aortic aneurysm (TAA, AAA) because it is less invasive. However, the effects of this procedure on vascular and cardiac function remain to be clarified. Methods: Echocardiographic study and the evaluation of the brachial-ankle pulse wave velocity (baPWV) were conducted before (pre-op) and after the endovascular stent grafting (post-op) in 24 consecutive patients with AAA or TAA. Patients were excluded if they had LV ejection fraction (EF) !50%, moderate-to-severe valvular diseases, aortic dissection and renal failure. Result: Post-op data were collected around 8 days after the operation. Blood pressure did not change, but baPWV was significantly elevated after the grafting (preop:1892 6 60, post-op:2094 6 84 cm/s; p ! 0.05). There was no difference in LV end-diastolic volume, LVEF, transmitral flow velocity curves or tissue-Doppler-derived mitral annular movement between pre-op and post-op status. However, LV mass (pre-op:154 6 8 g, post-op:163 6 8 g; p ! 0.05) and left atrial volume (preop:49 6 3 ml, post-op:51 6 3 ml; p ! 0.05) significantly increased at post-op status. The changes in LV mass were positively correlated with those in baPWV (p ! 0.05, R 5 0.44). Conclusion: The endovascular stent graft raised vascular stiffness and induced LV hypertrophy and left atrial enlargement within the short term after the operation in the absence of the changes in blood pressure. The long-term observational study is required to assess the influences of the stent grafting.

112 The Mobilization Day During Hospitalization Predicts 6 Minute Walking Distance at Time of Discharge in Patients With Chronic Heart Failure SUMIO YAMADA1, YUKO SHIMIZU2, YUJI KONO2, HISAKO OKUMURA2, FUMIHIKO MIYAKE3, TORU IZUMI4, PTMATCH COLLABORATIVE GROUP 1 Nagoya University, School of Health Sciences, Nagoya, Japan, 2Program in Physical therapy, Nagoya University Graduate School of medicine, Nagoya, Japan, 3Division of Cardiology, St, Marianna University School Medicine, Kawasaki, Japan,