pt053 insights into clinical impact of sarcomeric mutations in hypertrophic cardiomyopathy: mutation...
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Hospital, The University of Sydney and Anzac Research Institute, 7Cardiology, Royal PrinceAlfred Hospital and The University of Sydney, Sydney, Australia
Introduction: Patients with schizophrenia are at risk of acute myocarditis and dilated car-diomyopathy from clozapine use, and venous thromboembolism. Although guidelines advo-cate regular cardiac surveillance, the prevalence of subclinical cardiac dysfunction is unknown.Objectives: To assess the prevalence and predictors of subclinical cardiomyopathy afterlong-term clozapine use and investigate hypercoagulable state in schizophrenia and assess ifthis is associated with clozapine use.Methods: Consecutive patients with no cardiac history, with history of schizophrenia treatedwith either clozapine (group-1,n¼100) or non-clozapine antipsychotics (group-2,n¼21) for>1year, and age and sex-matched controls without schizophrenia (group-3,n¼20), underwentclinical, transthoracic echocardiography (TTE), biochemical (NT-proBNP & Hs Trop T) andcoagulation testing. TTE assessment included biplane left ventricular ejection fraction (LVEF) andLV 2D-speckle-tracking global longitudinal strain (LS). Hypercoagulability assessment included anovel Overall Hemostatic Potential assay to assess integrated coagulation and fibrinolysis.Results: Patients with schizophrenia received clozapine or non-clozapine antipsychotics for(mean�SD) 6.8�5.3 and 9.7�6.1years, respectively. Those on clozapine demonstratedimpaired LVEF (58.3�5.3% group-1 vs 62.2�5.3% group-2 vs 64.8�5.8% group-3,p<0.001), and LS (-16.7�2.1% group-1 vs -18.6�1.6% group-2 vs -20.2�2.3% group-3,p<0.001). Nine (9%) clozapine patients and no healthy controls or non-clozapine patients,had LVEF <50%. In the clozapine group, multivariate analysis showed elevated neutrophilcount and low HDL-cholesterol as the only independent associations with impaired LS. Plateletcount, D-dimer and fibrinogen levels did not differ between controls and patients withschizophrenia. In contrast, theoverall coagulationpotential (54.0�12.6vs45.9�9.1,p¼0.002),overall haemostatic potential (12.6�5.8 vs 7.2�3.7,p<0.001), and overallfibrinolytic potential(76.6�9.8% vs 84.9�6.4%,p<0.001) were all significantly different in patients with schizo-phrenia compared to controls and were unaffected by clozapine use.Conclusion: Asymptomatic LV impairment is common in patients with schizophreniareceiving long-term clozapine, and is associated with neutrophilia and low plasma HDLsuggesting an inflammatory link. There is also a hypercoagulable and hypofibrinolytic statein patients with schizophrenia unrelated to specific clozapine use.Disclosure of Interest: V. Chow: None Declared, T. Yeoh: None Declared, A. C. C. Ng:None Declared, T. Pasqualon: None Declared, E. Scott: None Declared, T. Chung: NoneDeclared, L. Thomas: None Declared, J. Curnow Consultancy for: Haematology consul-tative services to Novartis for the clozaril patient monitoring service, D. Celermajer: NoneDeclared, L. Kritharides: None Declared
PT052
“Idiopathic” dilated cardiomyopathy: biopsy proved markers of disease sub-entities
Virginija Grabauskiene1, Vyt_e Maneikiene*2, Jelena Celutkiene2, Kestutis Rucinskas21Pathology, Forensic Medicine and Pharmacology, 2Cardiovascular Diseases, Vilnius university,Medical faculty, Vilnius, Lithuania
Objectives: To identify biopsy proved etiopathogenetic markers of “idiopathic” dilatedcardiomyopathy (DCM) for diagnosis of distinct disease sub-entities and for possible eti-ology-directed treatment strategiesMethods: 36 patients (28 men, 41.9�11.6 years) with dilated cardiomyopathy (average leftventricle diastolic diameter 6.64�0.18 cm, EF 24.9�1.39%, mean PCWP-17.75�2.18)have undergone endomyocardial biopsy (EMB) examination including histology, immu-nohistochemistry (IHC) and viral genome detection by polymerase chain reaction (PCR).Results: On histological analysis the Dallas criteria was positive in 33 subjects (91.6 %),indicating borderline myocarditis. IHC staining revealed significant inflammatory cellularinfiltrates (�14 leucocytes/mm2 including up to 4monocytes/mm2with the presence of CD 3positive T-lymphocytes �7 cells/mm2 ) in 26 subjects (72.2%). Viral genome by PCR wasdetected in the myocardium of 15 subjects (41.7%), 3 of whom (8.3%) had double infectionsand 1 (2.8 %) – triple. The following virus species were detected: parvovirus B19 (n¼12,33.3%), human herpes virus type 6 (n¼4, 11.1%), enterovirus species, hepatitis C virus,varicella zoster virus, Epstein-Barr virus (n¼1, 2.8%) respectively. On the basis of the presenceor absence of viral genome in myocardium the patients was defined as virus-positive – 15(41.7%) and virus negative – 21 (58.3%). Based on viral genome in combination with IHCcharacterization of inflammation we discriminated four specific sub-groups of patients forpossible etiology-directed treatment strategies:1) Virus positive chronic myocarditis (virus+/IHC+) 12 (34.3%)– agent-specific antiviral therapy;2) Autoreactivemyocardial disease (virus-/IHC+) 14 (40.0%) – immunosuppressive or immunomodulatory therapy;3) Virus positivemyocardial disease (virus+/IHC-) 2 (5.7 %) – agent-specific antiviral therapy;4) No inflam-matory heart disease (virus-/IHC-) 7 (20.0 %) – conventional HF and arrhythmias treatment.Conclusion: Our approach of using immunohistochemical characterisation of inflamma-tion and virus-positive PCR as etiopathogenetic markers of inflammatory DCM should helpidentify specific subgroups of patients for etiology-directed treatment strategies and forrecruitment in future studies.Disclosure of Interest: None Declared
PT053
Insights Into Clinical Impact Of Sarcomeric Mutations In HypertrophicCardiomyopathy: Mutation Spectrum In A Large Cohort Of Unrelated ChinesePatients
Wenling Liu*1, Wen Liu1, Dayi Hu11cardiology, Peking Univ. People’s Hosp., Beijing, China
Introduction: Hypertrophic cardiomyopathy (HCM) is a hereditary heterogeneous car-diovascular disorder. But the clinical impact of its genetics has remained poorly elucidated.
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Objectives: We aimed to determine if the clinical characteristics correlate with differentgenotypes in a large cohort of Chinese patients.Methods: Direct sequencing of b-myosin heavy chain (MYH7), myosin binding protein-C(MYBPC3) and cardiac troponin T (TNNT2) genes was performed in 136 unrelated HANChinese HCM patients (27 familial and 109 sporadic cases) and their family members.Clinical evaluation and genotype-phenotype relationship analysis were performed for allprobands blinded to patient genotype.Results: In total, 32 mutations were identified in 36 patients (27%), including 10 novelones. Distribution of genes was 56.3% (MYBPC3), 31.3% (MYH7) and 12.5% (TNNT2).The occurrence of HCM-associated sarcomeric mutations were associated with an earlierage of onset, increased left ventricular hypertrophy, a higher incidence of syncope andsudden cardiac death and a family history. Patients with double mutations had an earlierage of onset, increased left ventricle thickness and more adverse events than those with asingle mutation. In contrast, no statistical difference was identified in the three underlyinggenes regarding the clinical characteristics and prognosis for any variable.Conclusion: MYBPC3 is the most predominant gene. A worse clinical phenotype andincreased adverse events were found in genotyped patients, especially in those with doublemutations. There was an association between the presence of two mutational defects andclinical expression and prognosis. However, target gene and mutation screening failed toprovide risk stratification among the individuals.Disclosure of Interest: None Declared
PT054
The safety and efficacy of prednisolone in preventing re-accumulation of ascitesamong EMF patients at Mulago Hospital: A randomised clinical trial(pilot)
Yvonne B. Nabunnya*1, James kayima11Medicine, Makerere College of Health Sciences, Kampala, Uganda
Introduction: Endomyocardial fibrosis is the commonest restrictive cardiomyopathyworldwide and is of unknown origin. Continuous inflammation and fibrosis in the heartand other parts of the body like the peritoneum may explain the exudative ascites. Ascitescauses acute discomfort and pain in these patients yet medical treatment is disappointing.Objectives: This pilot study, set out to determine the efficacy and safety of prednisolone inpreventing re-accumul ation of ascites from grade 2 to grade 3 among patients attendingMulago hospital cardiology service.Methods: This was a randomised placebo controlled trial with a 1:1 parallel design. Over aperiod of ten months, screening, recruitment and randomization to receive 1mg/Kg ofeither prednisolone or placebo if they met the eligibility criteria was done. Every four weeksfor a period of up to two months follow up was done. The primary outcome variables were;the proportion of patients receiving prednisolone prevented from re- accumulating ascitesfrom grade 2 to grade 3 at the end of treatment and, time to re-accumulation of ascites fromgrade 2 to grade 3. The safety of prednisolone was assessed using a questionnaireaddressing particular side effects as well as physical examination.Results: Sixteen patients were randomised to and received prednisolone, while nineteenwere randomised to and received placebo. Six patients were lost to follow up (1-pred-nisolone arm, 5-placebo). There were no statistically significant differences in the baselinedemographic, clinical and laboratory characteristics in the two arms of the study. Theefficacy of prednisolone was found to be 0.7 (95% confidence interval 0.439-1.114) andP-value 0.121. On survival analysis, the probability of progression to grade 3 ascites wasfound to be the same in both arms of the study. Prednisolone was found to be relatively safewhen used on these patients with no statistically significant difference in the occurrence ofthe different side effects monitored.Conclusion: Prednisolone was found to be relatively safe and can be used in this patientpopulation even if there was no statistically significant evidence of efficacy. We recommendfurther studies to test the relevance of autoimmunity in the aetiology and progression ofthis disease.Disclosure of Interest: None Declared
PT055
The relationship between admission time and baseline characteristics in patients withacute heart failure syndrome
Atsushi Mizuno*1, Koichiro Niwa21Cardiology, 2St.Luke’s International hospital, Tokyo, Japan
Introduction: Although there is significant relationship between in-hospital mortality/quality of care, treatment options, and regular hours admission in patients with acutemyocardial infarction, in patients with acute heart failure syndrome (AFHS) these effects arequestionable. Furthermore, we choose treatment options according to patients’ baselinecharacteristics in in AFHS patients.Objectives: To invetigate the relationship between patients’ baseline characteristics andtime of day of admission in AFHS.Methods: Total 2131 patients (Age;75.1�14.1, male n¼1176) with AFHS from July 2003to August 2011 were analyzed. We classified patient hospital arrival time, and retrospec-tively compared in-hospital mortality and vital signs between daytime (7a.m.-5p.m) andnighttime (5p.m.-7a.m.) as well as between regular hours (weekdays, 7a.m.-5p.m.) and off-hours (weekdays 5p.m.-7a.m. and weekends).Results: There is no significant differences between regular hours and off-hours. But thereare significant differences in vital signs between daytime and nighttime. In both mortalitycomparisons, there are no significant differences between two groups, but nighttimeseemed relatively worse. Furthermore, the rate of AHFS without volumeoverload is follows;daytime28.6% vs nighttime34.0% (p<0.001), regular hours31.4% vs off-hours30.3%(p¼0.723).
GHEART Vol 9/1S/2014 j March, 2014 j POSTER/2014 WCC Posters