PS163 Tenascin-C Levels and Clinical Importance in Pulmonary Arterial Hypertension Associated With Congenital Heart Disease

POSTER ABSTRACTS

PS157 The Relationship Between Heart Rate Recovery and the Levels of Catestatin After Acute Myocardial Infarction W. Zhao*1, Y. Liu1, L. Zu1, W. Gao1 1 Cardiology, Peking University Third Hospital, Beijing, China Introduction: Autonomic nervous dysfunctions are closely related to the occurrence, development and prognosis of acute myocardial infarction (AMI). Heart rate recovery after exercise (HRR)is a common clinical evaluated index of autonomic nervous function, which reflects autonomic balance under treadmill exercise. Our preliminary study showed that plasma levels of catestatin (CST) were increased gradually, and inversely associated with norepinephrine during the early phase of AMI, which indicated that CST might play an important role in regulation of autonomic nervous system after AMI. However there are few studies about the relationship between HRR and CST after AMI. Objectives: To investigate the relationship between HRR and CST in patients with acute ST segment elevation myocardial infarction (STEMI) treated with primary PCI. Methods: A total of 80 STEMI patients with blood sample were retrospectively investigated. All the patients were conducted cardiopulmonary exercise testing(CPET)within 30 days after STEMI, and heart rate recovery at 1 minute and 2 minute (HRR1,HRR2) were calculated. Levels of plasma CST in patients with blood samples before primary PCI were detected by ELISA, and the correlation between CST and HRR were investigated. Results: Mean plasma concentration of CST in those patients before PCI was 4.30
0.61 ng/ml. The plasma levels of CST were positively associated with HRR1(r¼0.234,p¼0.037) and HRR2(r¼0.238, p¼0.033). Multiple linear regression analysis demonstrated CST was independently positively correlated to HRR1 and HRR2. Conclusion: Lower Catestain level is an independently predicting factor of autonomic nervous dysfunction in STEMI. Disclosure of Interest: None Declared PS158 Determinants of Heart Rate Recovery for Patients With Primary PCI After ST-Elevation Myocardial Infarction W. Zhao*1, Y. Liu1, L. Zu1, W. Gao1 1 Cardiology, Peking University Third Hospital, Beijing, China Introduction: The majority of patients with acute myocardial infarction (AMI) are associated with autonomic nervous dysfunctions, which are closely related to the prognosis of AMI. Heart rate recovery after exercise (HRR) is a common clinical evaluated index of autonomic nervous function. However there are few studies about the determinants of HRR. Objectives: To investigate the determinants of HRR in patients with acute ST segment elevation myocardial infarction (STEMI) treated with primary PCI. Methods: A total of 260 patients were retrospectively investigated from July 2011 to December 2014. All the patients were conducted cardiopulmonary exercise testing(CPET)within 30 days after STEMI, and heart rate recovery at 1 minute and 2 minute (HRR1, HRR2) were calculated. The correlation among HRR with clinical characteristics, biochemical measurements,echocardiographic parameters and exercise tolerance was analysed. Results: The mean HRR1 was 25.97
12.17 bpm and mean HRR2 was 43.76
13.32 bpm in the whole study population. HRR1 was positively correlated to peak oxygen uptake(VO2peak) (r¼0.129, p<0.001¼,while negatively associated with age (r¼-0.140,p¼-0.026), the value of the ratio of early transmitral flow velocity to early diastolic velocity of mitral annulus (E/Em) (r¼-0.172, p¼0.003), and left atrial pressure( LAP) (r¼-0.186,p¼0.003). Multiple linear regression analysis demonstrated that VO2peak was independently positively associated with HRR1, while LAP, heart rate during recovery phase of STEMI and age was negatively correlated to HRR1. HRR2 was positively correlated to VO2peak (r¼0.288, p<0.001¼, while negatively associated with age (r¼ -0.242, p<0.001¼, E/Em (r¼-0.255, p<0.001¼, and LAP (r¼-0.279, p<0.001). Multiple linear regression analysis demonstrated that VO2peak was positively associated with HRR2, while LAP, E/Em and age were negatively correlated to HRR2. Conclusion: Lower exercise tolerance in STEMI patients is associated with abnormal HRR. Disclosure of Interest: None Declared PS160 Inflammatory Thoracic Aortic Aneurysms and Dissections T. Strecker*1, A. Agaimy2, M. Weyand1 Center of Cardiac Surgery, 2Institute of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany

1

Introduction: Aortic aneurysms represent one of the major causes of cardiovascular surgery. Their etiology varies greatly based on patient’s age and other clinicopathologic determinants. In addition to common atherosclerotic vascular diseases, an inflammatory etiology, in particular IgG4-related disease (IgG4-RD) has increasingly emerged as a cause of dissecting inflammatory aortic aneurysms (IAA). Objectives: Aortic aneurysms represent one of the major causes of cardiovascular surgery. Their etiology varies greatly based on patient’s age and other clinicopathologic determinants. In addition to common atherosclerotic vascular diseases, an inflammatory etiology, in particular IgG4-related disease (IgG4-RD) has increasingly emerged as a cause of dissecting inflammatory aortic aneurysms (IAA).

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Methods: To assess the frequency and types of IAA, we reviewed all cases of aortic aneurysms resected at our Erlangen Heart Center during 2000-2013. 376 patients underwent resection of aortic aneurysms in the study period. These are further categorized as ascending aortic aneurysms (45%), aortic arch aneurysm (2%), descending aortic aneurysm (3%), type A dissection (46%) and type B dissection (4%). Results: Fifteen cases (4%) showed variable lymphoplasmacytic inflammation thus qualifying as IAA. Affected were 9 females and 6 males (female to male ratio ¼ 1.5: 1). None was known to have IgG4-RD and serum IgG4 and/ or IgG levels (known in 6 cases) were normal. Variable sclerosing lymphoplasmacytic inflammation was seen either confined to the adventitia (periaortitis; mainly in males) or extending through all layers (mainly in females). A wide range of IgG4 plasma cells were detected. Lymphoid follicle and variable fibrosis were common but obliterative phlebitis was not seen. Conclusion: IgG4-rich sclerosing lymphoplasmacytic thoracic aortitis is a constant histological feature of thoracic IAA. Normal serum IgG4 in most patients, predilection for women and absence of other features of IgG4-RD all suggest a tissue-specific localized autoimmunological process and argue against a systemic disorder. The relationship of IgG4-rich lymphoplasmacytic thoracic aortitis in those patients with IAA lacking other organ manifestations or an elevated serum IgG4 level to systemic IgG4-RD remains unclear and merit further studies. Disclosure of Interest: None Declared PS162 Integrating Pro-Bnp and Pedometer to the 6MWT in Patients With PH in Public Hospital Center of Argentina V. Gregorietti*1, S. Perrone1, A. Machain1, R. Gamboa1, C. Tajer1, A. Estevez1, D. Aimone1, R. Sarmiento1, on behalf of Grupo de estudio y Tratamiento de Hipertension Pulmonar Hospital El Cruce 1 29819, Buenos Aires, Argentina Introduction: The walk test six minutes, as we all know, is a prognostic marker, both at the time of diagnosis, and monitoring and adjusting the treatment, which is why the goal of our work is to search an index into this test that allows us definer of more accurate manner, in accordance with not only the parameters measured in a standardized way but add a count steps (pedometer) and proBNP levels at the time when performing the test. Objectives: To evaluate the association between basal level pro-BNP and the number of footsteps measured by a digital pedometer during the 6MWT, and ohter parameters of clinical and prognostic relevance. Methods: To evaluate the association between basal level pro-BNP, the number of footsteps measured by a digital pedometer during the 6MWT and ohter parameters of clinical and prognostic relevance. We prospectively analized 118 consecutive 6MW tests from 118 patients with pulmonary hypertension(PH) with different etiologies according to ESC 2015 classification, in outpatient monitoring in our center. The statistical method was used SPSS. Results: Mean age was 49 years (SD 6.4 years), and 73 % of the population was female. Mean 6MWD was 323 mts (18-520), mean number of footsteps was 586 (42-1290). Mean pro-BNP levels were 270 pg/ml (14- 1110). The correlation between pro-BNP levels, the number of footsteps, the 6MWD and WHO functional class was analyzed. We found a significant association between pro-BNP levels and the number of footsteps (p¼0.001) and WHO functional class (p¼0.009). Conclusion: The number of footsteps during the 6MWT correlates inversely with clinical and laboratory parameters of prognostic relevance in patients with PH such as pro-BNP levels and WHO functional class. The number of footsteps measured with a digital pedometer during the 6MWT might provide valuable data for evaluation and follow up of patients with PH. Disclosure of Interest: None Declared PS163 Tenascin-C Levels and Clinical Importance in Pulmonary Arterial Hypertension Associated With Congenital Heart Disease O. Vuran*1, M. Kayikcioglu2, S. Nalbantgil2, O. Musayev3, H. S. Kemal4, N. Mogulkoc5, L. C. Hurkan2, H. Kultursay2 1 Cardiology, Alasehir State Hospital, Manisa, 2Cardiology, Ege University Medical Faculty, Izmir, Turkey, 3Cardiology, Central Clinic, Baku, Azerbaijan, 4Cardiology, Near East University, Nicosia, Cyprus, 5Pulmonology, Ege University Medical Faculty, Izmir, Turkey Introduction: In Pulmonary arterial hypertension (PAH), prognostic value of some biomarkers like BNP/NT-proBNP has been shown and used in the routine course of the disease. Tenascin-C (TNC) is an extracellular matrix glycoprotein and has a great importance in the pathophysiology of PAH, but clinical relevance is unknown. Objectives: In this study, the relationship of TNC levels measured in patients with PAH associated with congenital heart disease (PAH-CHD), disease prognostic markers and adverse events in short-term follow-up (1 year) were investigated. Methods: Thirty-four PAH-CHD patients (age: 31
8.3, 20 females) followed in our centre were age and sex matched with 21 healthy volunteers and plasma TNC levels were measured using ELISA. Also, 6-minute walk test (6-MWT), transthoracic echocardiography performed and baseline NT-proBNP levels were measured simultaneously. Clinical monitoring of patients for the development of adverse events (right heart failure, syncope, hospitalization and death) took place. Results: TNC levels in patients with PAH-CHD were significantly higher compared to healthy group (respectively 61.5
20.4 ng/ml, 13.3
6.4 ng/ml, p<0.0001). There was a significant

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PS164 Underdosing of Noacs for AF: Old Habits Die Hard T. J. Ford1,2, A. Cheng*1, G. Youssef2, M. Sader2, D. Rees2 1 Medicine, University of New South Wales, 2Cardiology, St George Hospital, Sydney, Australia Introduction: Many physicians hold a bias against anticoagulation for atrial fibrillation (AF) on account of their perception of unacceptably high bleeding risk for their patient. This risk-averse tendency with fear of bleeding may be responsible for underdosing with warfarin (“low-intensity anticoagulation”) despite a proven lack of efficacy without improved safety with this strategy. Whilst underdosing with warfarin is common, there is little known about the extent of nonVitamin K antagonist (VKA) anticoagulant (NOAC) underdosing in contemporary practice. Objectives: This study was the first in Australia to specifically identify the proportion of underdosed “real-world” patients treated with a NOAC in our tertiary centre. Methods: All new prescriptions of reduced dose apixaban and rivaroxaban were analysed from centralized electronic records between 01/04/2014 and 31/03/2015. Based on the strict criteria for dose reduction in the ROCKET-AF and ARISTOTLE trials, the appropriate dose of NOAC was determined from analysis of the electronic medical record and medical notes. Information including patient weight, creatinine clearance, age, sex and other variables including co-prescription with antiplatelet agents and specialty of initiating physician were collected. Results: A total of 82 new patients with AF prescribed reduced dose apixaban and rivaroxaban were identified. 10 patients were excluded due to insufficient data to determine the correct NOAC dose. Over half (55.6%) of all reduced dose NOAC prescriptions were underdosed. The mean age of patients studied was 81.0 +/- 8.1 years. The only significant variable associated with NOAC underdosing was younger age (mean age 78.5 versus 84.1, p¼0.001). Other recorded variables were not significantly associated with underdosing. Conclusion: Underdosing rivaroxaban and apixaban is common in the treatment of “realworld” patients with AF. Whilst it is unclear whether this strategy translates to increased

Age

Underdosed NOAC

Appropriate Dose Reduction

78.5 +/- 9.1

84.1 +/- 5.3

p¼0.001

Cardio

34 (85%)

26 (81.3%)

p¼n/s

Non cardio

6 (15%)

6 (18.8%)

F

21 (52.5%)

19 (59.4%)

M

19 (47.5%)

13 (40.6%)

Apixaban

20 (50%)

21 (65.6%)

Rivaroxaban

20 (50%)

11 (34.3%)

Specialty

Sex

Drug

Antiplatelet

Yes

6 (15%)

4 (12.5%)

No

34 (85%)

28 (87.5%)

40 (55.6%)

32 (44.4%)

Total

p¼n/s

p¼n/s

p¼n/s

rates of stroke or a benefitical safety profile, this study highlights the important issue of appropriate NOAC dosing according to combined patient-physician treatment goals. Disclosure of Interest: None Declared

specified LDL-C level was not met at Week 8; 2 studies used 150 mg Q2W throughout. Background statin dose remained constant; ATV doses ranged from 10–80 mg; RSV 5–40 mg; SMV 10–80 mg. Mean % LDL-C reduction from baseline to 24 weeks was analyzed in subgroups according to statin and dose. For efficacy analyses, studies were pooled by initial alirocumab dose and control; for safety, studies were pooled by control group. Results: Significant LDL-C reductions were observed with alirocumab across all subgroups, with no association between statin dose and the magnitude of reduction. In studies using a starting dose of alirocumab 75 mg Q2W (with possible Week 12 dose increase to 150 mg Q2W), Week 24 mean LDL-C reductions from baseline ranged from 46.2–51.5% with different doses of ATV, 44.2–53.9% with RSV and 41.0–51.9% with SMV (ranges of pooled mean reductions across all doses within each statin group). In studies of alirocumab 150 mg Q2W throughout, Week 24 mean LDL-C reductions from baseline were 58.9– 62.9% with different doses of ATV, 54.5–60.1% with RSV and 52.8–62.6% with SMV. Interaction P values across all statin doses were not significant, indicating no relation between background statin dose and the level of LDL-C reduction at Week 24. Across the 8 trials, incidence of treatment-emergent adverse events (TEAEs) was generally similar between alirocumab and control patients. In the placebo-controlled pool, TEAEs reported by 5% of either group were arthralgia, back pain, headache, influenza, injection site reaction, nasopharyngitis, upper respiratory tract infection (URI) and urinary tract infection; in ezetimibe-controlled studies these were accidental overdose and URI. Conclusion: The LDL-C-lowering effect of alirocumab does not vary significantly according to background ATV, RSV or SMV dose. Disclosure of Interest: A. Catapano Grant/research support from: AstraZeneca, Amgen, Aegerion, Eli Lilly, Genzyme, Mediolanum, Merck, Pfizer, Rottapharm, Recordati, Sanofi, Sigma-Tau, Consultancy for: Amgen, Merck, Pfizer, Sanofi, Employee from: University of Milan, Honorarium from: AstraZeneca, Amgen, Aegerion, Eli Lilly, Genzyme, Mediolanum, Merck, Pfizer, Rottapharm, Recordati, Sanofi, Sigma-Tau, L. V. Lee Employee from: Sanofi , M. Louie Shareholder of: Regeneron , Employee from: Regeneron, D. Thompson Consultancy for: Regeneron Pharmaceuticals, Inc., J. Bergeron Consultancy for: Sanofi, Regeneron, Amgen PS166 Efficacy and Safety of Alirocumab According to Smoking Status A. C. Sposito*1, F. A. Fonseca2, M. Averna3, L. V. Lee4, M. J. Louie5, G. Asset6, M. Farnier7 1 Cardiology Division, State University of Campinas School of Medicine (FCM Unicamp), Campinas, 2Department of Medicine, Cardiology Division, Federal University of Sao Paulo, Sao Paulo, Brazil, 3Dept. of Biomedicine, Internal Medicine and Medical Specialties- DI.BI.MIS, School of Medicine, University of Palermo, Palermo, Italy, 4Sanofi, Bridgewater, 5Medical Affairs, Regeneron Pharmaceuticals, Inc., Tarrytown, United States, 6Sanofi, Chilly-Mazarin, 7Point Médical, Dijon, France Introduction: Studies have suggested that smokers have higher circulating levels of PCSK9 than non-smokers. We analyzed whether differential effects were seen with alirocumab treatment in smokers and non-smokers. Objectives: To assess whether current smoking status has any impact on the efficacy and safety of alirocumab. Methods: Efficacy and safety were assessed according to current smoking status from 10 Phase 3 studies. Efficacy data were pooled according to alirocumab dose, comparator group (placebo or ezetimibe) and background statin use, resulting in four different pools. Results: 947 smokers and 4036 non-smokers were randomized. Both groups had more males than females and w90% were white. Non-smokers tended to be slightly older with a higher BMI compared with smokers. Where measured, baseline PCSK9 levels were similar between groups. Significant reductions in LDL-C level from baseline at Week 24 were seen with alirocumab, with a consistent effect in smokers and non-smokers (Tables). Across the 10 studies, the incidence of treatment-emergent adverse events (TEAEs) was generally similar between alirocumab and control patients, irrespective of smoking status. Conclusion: Alirocumab significantly reduced LDL-C levels regardless of smoking status, with no observed differences in efficacy or safety between smokers and non-smokers. PCSK9 levels were similar between the two groups at baseline. Table 1. LS mean (SE) change in LDL-C (%) from baseline to Week 24 : placebo-controlled studies, background statin +/- other lipid-lowering therapy Current Smoker

PS165 Alirocumab Efficacy is Independent of Background Statin Type or Dose A. L. Catapano*1, L. V. Lee2, M. J. Louie3, D. Thompson4, J. Bergeron5 1 Department of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica, Milan, Italy, 2Sanofi, Bridgewater, 3Medical Affairs, 4Regeneron Pharmaceuticals, Inc., Tarrytown, United States, 5Clinique des Maladies Lipidiques, Département de Médecine, CHU de Québec, Québec, Canada Introduction: Statins increase PCSK9 plasma levels, which may potentially affect alirocumab efficacy due to partial elimination via PCSK9-mediated clearance. Objectives: To investigate whether the LDL-C lowering efficacy of alirocumab varies by dose of concomitant atorvastatin (ATV), rosuvastatin (RSV) or simvastatin (SMV). Methods: 8 Phase 3 studies (4629 randomized patients; 24-104 weeks) that utilized background statin therapy were analyzed. Patients received alirocumab every 2 weeks (Q2W) or control (placebo/ezetimibe) on a background of statin +/- other lipid-lowering therapy. In 6 studies, alirocumab dose increased from 75 to 150 mg at Week 12 if a pre-

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ALI 75/150y mg Q2W vs PBO

ALI 150 mg Q2W vs PBO

y z

W24 ALI

W24 PBO

Interaction pvaluez

Yes

n[114 -51.8% (2.6)

n[62 6.6% (3.6)

0.17

No

n[579 -47.9% (1.1)

n[288 3.7% (1.6)

Yes

n[330 -59.5% (1.6)

n[167 0.2% (2.3)

No

n[1271 -60.6% (0.8)

n[648 0.6% (1.1)

0.64

Dose increased from 75 to 150 mg Q2W at W12 if W8 pre-defined LDL-C level not reached Smoker vs non-smoker

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POSTER ABSTRACTS

positive correlation between TNC levels in the patient group and right atrial area (RAA) (r¼0.518, p¼0.003) and NT-proBNP (r¼0.503, p¼0.003) levels, whereas there was a significant negative correlation with tricuspid annular plane systolic excursion (TAPSE, r¼-0.389, p¼0.034). No significant relationship was observed between TNC levels and functional class (r¼0.296, p¼0.089) and 6-MWT distance (r¼-0.087, p¼0.625). Also, there was a significant relationship between plasma TNC levels and all follow-up adverse events (Rho¼0.538, p¼0.001). Conclusion: Plasma TNC levels were significantly higher in PAH-CHD. There is a significant relation between TNC levels and parameters with proved prognostic value in PAH, such as TAPSE, RAA and NT-proBNP levels. Also, there was a significant relationship between TNC levels and adverse events associated with PAH during follow-up. All of these data suggest that TNC levels in patients with PAH-CHD may be a new prognostic biomarker. Further studies are needed to confirm this statement. Disclosure of Interest: None Declared