75 CONGRESSO NAZIONALE della Società Italiana di Cardiologia ORALI

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1 ORALI CONCORSO GIOVANI RICERCATORI O1 LEFT ATRIAL FUNCTION ANALYSIS AS INDEPENDENT PARAMETER TO PREDICT LEFT VENTRICULAR END DIASTOLIC PRESSURE MATTEO CAMELI (A), MASSIMO FINESCHI (A), STEFANIA SPARLA (A), MATTEO LISI (A), FLAVIO D ASCENZI (A), MAURIZIO LOSITO (A), MARTA FOCARDI (A), ROBERTO FAVILLI (A), CARLO PIERLI (A), SERGIO MONDILLO (A) (A) DEPARTMENT OF CARDIOVASCULAR DISEASES, UNIVERSITY OF SIENA BACKGROUND: Several noninvasive measurements are widely applied to estimate left ventricular filling pressures (LVFP) and to establish a correct therapeutic strategy in a lot of cardiac diseases, especially in patients with heart failure. Among these, left atrial (LA) deformation analysis by speckle tracking echocardiography (STE), has recently demonstrated to be highly accurate to estimate LVFP even in patients with advanced heart failure. The aim of this study was to examine the accuracy of LA strain in predicting LVFP, analyzing its dependency from left ventricular parameters. METHODS: A total of 87 stable patients with sinus rhythm undergoing cardiac catheterization were studied. LV end diastolic pressure (LVEDP) was obtained during cardiac catheterization; peak atrial longitudinal strain (PALS), left ventricular longitudinal strain (GLS) and mitral annular plane systolic excursion (MAPSE) were measured in all subjects by another independent operator. PALS values were obtained by averaging all segments (global PALS), and by separately averaging segments measured in the 4-chamber and 2-chamber views. RESULTS: Global PALS correlated significantly with LVEDP (r=-0.86; p<0.0001). Lower levels of correlation were found for E/E ratio (r=0.57; p=0.01), GLS (r=0.40; p=0.05) and MAPSE (r=- 0.22; p=ns). Parameters of LV systolic analysis presented lower correlation in subgroup of patients with lower LV ejection fraction. ROC analysis showed global PALS as the best predictor of increased LVEDP (AUC: 0.83). In multivariate analysis, global PALS emerged as a determinant of the LVEDP, independently on other confounding factors. CONCLUSIONS: In comparison to E/E ratio and LV systolic parameters, LA strain is a strong and independent parameter for non invasive prediction of LVEDP. O2 PREVALENCE, CLINICAL CORRELATES AND FUNCTIONAL IMPACT OF SUBAORTIC VENTRICULAR SEPTAL BULGE (FROM THE BALTIMORE LONGITUDINAL STUDY OF AGING) MARCO CANEPA (A, B, C), PIETRO AMERI (A), GIANPAOLO BEZANTE (A), MAJD ALGHATRIF (B), JAMES STRAIT (B), EDWARD LAKATTA (B), LUIGI FERRUCCI (B), THEODORE ABRAHAM (C), CLAUDIO BRUNELLI (A) (A) CARDIOLOGY UNIT, DEPARTMENT OF INTERNAL MEDICINE, UNIVERSITY OF GENOVA, IRCCS AOU SAN MARTINO IST, GENOVA, IT; (B) LONGITUDINAL STUDY SECTION, TRANSLATIONAL GERONTOLOGY BRANCH NATIONAL INSTITUTE ON AGING, NIH, BALTIMORE MD, USA; (C) HYPERTROPHIC CARDIOMYOPATHY UNIT DIVISION OF CARDIOLOGY, JOHNS HOPKINS UNIVERSITY, BALTIMORE MD, USA 1

2 BACKGROUND: A localized hypertrophy of the subaortic segment of the ventricular septum - ventricular septal bulge (VSB, Figure 1) - has been frequently described in series of elderly persons, but its prevalence with age, clinical correlates and impact on cardiac function and exercise capacity remain uncertain. METHODS: We explored these associations in a cross-sectional sample without known cardiac disease from the Baltimore Longitudinal Study of Aging. We randomly selected 700 participants (50% men, mean age 64±15, range years) and reviewed their echocardiograms*. RESULTS: We identified 28 men and 21 women with VSB (7% overall prevalence). The prevalence of VSB significantly increased with age in both genders (Figure 2, p<.0001). In multivariate logistic regression including hypertension and other cardiovascular risk factors, only age displayed a significant independent association with VSB (OR 1.06 per year, 95% CI , p=0.0001). After multiple adjustments, participants with VSB as compared to those without had enhanced global left ventricular contractility (fractional shortening 41±1.3 vs. 38±0.3%, p=0.04; ejection fraction 71±1.6 vs. 67±0.4%, p=0.06; systolic velocity of the mitral annulus 8.4±0.1 vs. 8.9±0.3, p=0.06), and larger aortic root diameters (3.3±0.06 vs. 3.1±0.02 cm, p=0.02). In subgroup of participants who completed a maximal treadmill test (177 women and 196 men), those with VSB (19, 5.1%) had significantly lower peak oxygen consumption than their counterparts (19.6±3.8 vs. 22.9±6.6 ml/kg per minute, p=0.03). However this association was no longer significant after multiple adjustments. CONCLUSIONS: The presence of VSB is independently associated with older age, determines enhanced left ventricular contractility, without any evident impact on exercise capacity. FIGURE 1. Example of VSB. FIGURE 2. Prevalence of VSB *From the two-dimensional parasternal long-axis view at end-diastole, the presence of VSB was defined as i) a proximal focal area of localized septal hypertrophy with a dune-like structure protruding in the left ventricular outflow tract, ii) a thickness 13 mm in men and 12 mm in women, and iii) more than 50% greater than the thickness of the septum at its mid-distal-point. 2

3 O3 LEFT ATRIAL BLOOD FLOW VELOCITY DISTRIBUTION: A COMBINED 4D FLOW MRI, T1 MAPPING MRI AND DOPPLER ECHOCARDIOGRAPHY STUDY CARLA CONTALDI (A, B), BRADLEY ALLEN (C), LUBNA CHOUDHURY (B), DANIEL C. LEE (B, C), PIM VAN OOIJ (C), SANDRO BETOCCHI (A), MICHAEL MARKL (C), ROBERT O. BONOW (B) (A) DEPARTMENT OF ADVANCED BIOMEDICAL SCIENCES, FEDERICO II UNIVERSITY SCHOOL OF MEDICINE OF NAPLES, ITALY; (B) DEPARTMENT OF MEDICINE CARDIOLOGY, NORTHWESTERN UNIVERSITY FEINBERG SCHOOL OF MEDICINE, CHICAGO, IL, USA; (C) DEPARTMENT OF RADIOLOGY, NORTHWESTERN UNIVERSITY FEINBERG SCHOOL OF MEDICINE, CHICAGO, IL, USA Background: New MRI techniques (T1-mapping, 4D flow MRI) provide quantitative assessment of myocardial extracellular volume fraction (ECV) as a measure of fibrosis as well as the in-vivo assessment of 3-directional blood flow within the entire heart including the atria. Objectives: To investigate if alterations in left ventricular (LV) diastolic function in hypertrophic cardiomyopathy (HCM) are associated with increases in LV ECV and alterations in left atrial (LA) blood flow dynamics. Methods: 4D flow MRI and T1-mapping MRI were performed in 22 HCM patients (mean 53±14 years) and 15 age matched controls (mean 56±5 years). For all 4D flow data, the LA was 3D segmented and LA mean blood flow velocity was quantified. T1 values for each slice were acquired pre and post contrast agent administration, by drawing contours along the endocardial and epicardial borders and a region of interest in the left ventricular blood pool. ECV was calculated as reported by Messroghli DR et all and it was averaged over the base, mid and apex to estimate whole heart ECV. Diastolic function was assessed by echo-doppler in 16 of the 22 HCM patients prior to MRI. Results: All HCM patients were in sinus rhythm without history of paroxysmal atrial fibrillation (AF); 6 patients had left ventricular outflow tract obstruction. LA mean velocities in HCM patients (0.27±0.07 m/s) were significantly increased compared to controls (0.21±0.03 m/s, p=0.009) and more heterogeneously distributed (Figure A), but were not significantly different in patients with and without obstruction and with or without mild mitral regurgitation (MR) and moderate or severe MR. There were significant correlations between LA velocities and ECV (r=0.48; p=0.02) (Figure B), ECV and LA volume index (LAVI) (r=0.7; p<0.001), ECV and E/e (r=0.5; p=0.04), LA velocities and LAVI (r=0.55; p=0.02) and LA velocities and E/e (r=0.67; p=0.04). Conclusion: HCM patients showed a significant difference in 3D LA flow compared to controls. The increased mean velocity may be an index of increased interstitial tissue and diastolic dysfunction in these patients. These novel functional measures may be useful in assessing severity of HCM and risk stratification, particularly the risk of future AF, and warrant further longitudinal investigation. 3

4 O4 TUTTE LE PROTEINE DEL SURFACTANTE SONO MARCATORI BIOLOGICI DI DANNO DELLA MEMBRANA ALVEOLO-CAPILLARE NELL INSUFFICIENZA CARDIACA CRONICA? PAOLA GARGIULO (A), CRISTINA BANFI (B), STEFANIA GHILARDI (B), DAMIANO MAGRI (C), MARTA GIOVANNARDI (B), ELISABETTA SALVIONI (B), ELISA BATTAIA (B), PASQUALE PERRONE-FILARDI (A), ELENA TREMOLI (E), PIERGIUSEPPE AGOSTONI (B) (A) DIPARTIMENTO DI SCIENZE BIOMEDICHE AVANZATE, UNIVERSITA DEGLI STUDI DI NAPOLI, FEDERICO II, NAPOLI, ITALIA; (B) CENTRO CARDIOLOGICO MONZINO, IRCCS, MILANO, ITALIA; (C) DEPARTIMENTO DI MEDICINA CLINICA E MOLECOLARE, UNIVERSITA LA SAPIENZA, ROMA, ITALIA; (D) DIPARTIMENTO DI MEDICINA, UNIVERSITA DI VERONA, VERONA, ITALIA; (E) DIPARTIMENTO DI SCIENZE FARMACOLOGICHE E BIOMOLECOLARI, UNIVERSITA DI MILANO, MILANO, ITALIA; (F) DEPARTIMENTO DI SCIENZE CLINICHE E MEDICINA DI COMUNITA, UNIVERSITA DI MILANO, MILANO, ITALIA Razionale: Nei pazienti affetti da insufficienza cardiaca cronica (ICC), la barriera alveolo-capillare è frequentemente compromessa e la presenza di alterazioni funzionali e strutturali ha un riconosciuto ruolo prognostico, oltre a rappresentare un interessante target terapeutico. Il recettore per i prodotti avanzati di glicosilazione (RAGE) e le proteine del surfactante (SP), sebbene siano state proposte come biomarcatori di danno polmonare, e più specificamente di alterazione della membrana alveolocapillare, sono state poco studiate nell ICC. Obiettivo: Identificare nei pazienti affetti da ICC quale tra le SP e RAGE sia la proteina che meglio identifichi la presenza di disfunzione della membrana alveolo-capillare, misurata mediante lo studio della diffusione alveolo-capillare polmonare del monoossido di carbonio (DLCO). Metodi: Abbiamo arruolato 89 pazienti affetti da ICC in stabile compenso da almeno 3 mesi e 17 controlli sani appaiati per sesso ed età. Tutti i soggetti sono stati sottoposti a ecocardiogramma transtoracico con misura della frazione di eiezione del ventricolo sinistro (FEVS), a prelievo venoso per il dosaggio dei comuni parametri biochimici e del peptide natriuretico (BNP), a DLCO e a test da sforzo cardiopolmonare con misura del consumo di ossigeno al picco (VO2 di picco) e della pendenza della relazione tra la ventilazione e ila produzione di anidride carbonica (VE/VCO2 spole). Abbiamo dosato i livelli plasmatici della forma immatura della SP-B, della forma matura dell SPB, di SP-A, di SP-D e di RAGE. Risultati: I livelli plasmatici della forma immatura di SP-B, di SP-A e di SP-D, ma non della forma matura di SP-B e di RAGE sono risultati significativamente più elevati nei pazienti affetti da ICC rispetto ai controlli (SP-B immatura: 15.6 AU (25-75 range interquartile (RI): ,) vs 11.1 (RI: ) (p = 0.000); SP-A: 29.9 ng/mg (RI: ) vs 18.3 (RI: (p = 0.01); SP-D: 125 ng/mg (RI:85-172) vs 88 (RI:72-125) (p = 0.02); SP-B matura: 190 ng/mg (RI: ) vs 244 (RI: ) (p = ns); RAGE: 1485 pg/mg (RI: ) vs 1236 (RI: ) (p = ns). Nei pazienti affetti da IC, i livelli plasmatici della forma immatura di SPB, di SP-A e SP-D sono risultati significativamente più alti nei pazienti in III e IV classe NYHA rispetto ai pazienti in I e II classe NYHA. I livelli plasmatici della forma immatura di SPB, di SP-A, di SP-D e di RAGE sono risultati significativamente correlati con i valori di DLCO, con i valori di VO2 di picco, con i valori della VE/VCO2 spole e con i livelli plasmatici di BNP. I livelli plasmatici della forma matura di SP-B non sono risultati correlati con nessuno di questi parametri. Confrontando i coefficienti di correlazione tra i suddetti parametri e le singole proteine, la forza della correlazione tra i livelli plasmatici della forma immatura di SPB e i valori di DLCO è risultata significativamente maggiore rispetto alla forza delle correlazioni esistenti tra le altre proteine e i valori di DLCO. Questo risultato è stato confermato all analisi multivariata che ha dimostrato l associazione indipendente tra i valori plasmatici della 4

5 forma immatura di SP-B e i valori di DLCO. Conclusione: La forma immatura di SP-B è il più affidabile marcatore biologico della funzione della membrana alveolo-capillare nei pazienti affetti da ICC. O5 PROGNOSTIC VALUE OF LOW PLASMA ABSOLUTE LYMPHOCYTE COUNT IN PATIENTS ADMITTED FOR ACUTE HEART FAILURE VALENTINA CARUBELLI (A), CARLO LOMBARDI (A), ANDREA ZANOLETTI (A), VALENTINA LAZZARINI (A), FILIPPO QUINZANI (A), FEDERICA ZILIANI (A), LEVI GUIDO (A), ANDREA VIGNONI (A), SARA PELLIZZARI (A), ENRICO VIZZARDI (A), MARCO METRA (A) (A) CATTEDRA DI CARDIOLOGIA UNIVRSITA E SPEDALI CIVILI DI BRESCIA Background: Low relative lymphocyte count is an important prognostic marker in acute heart failure (AHF), however it could be influenced by other abnormalities in white cells count. Our purpose is to evaluate if low absolute lymphocyte count (ALC) is an independent predictor of events in patients with AHF. Methods: In a retrospective analysis, we included 309 patients with AHF, divided in 2 groups according to the median value of ALC at admission (1,410 cells/mm3). The primary end point was all-cause mortality within 1 year. Results: Patients with low ALC were older and had more comorbidities, namely atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease (COPD) and anemia. Low ALC was associated with higher all-cause mortality (27.1% vs 17.5%; p=0.020). In a multivariable model, the independent predictors of mortality at one year were low ALC (HR 1.71; IC 95% [ ]; p=0.035), systolic blood pressure at admission (HR 1.17; IC 95% [ ]; p=0.009) and glomerular filtration rate (HR 0.96; IC 95% [ ]; p<0.001). Conclusion: Low ALC in patients with AHF is an independent prognostic marker, underscoring that the immune system derangement may play an important role in the pathophysiology of this disease. 5

6 O6 ALEXITHYMIA ON TOTAL ISCHEMIC TIME IN PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION: A PRELIMINARY STUDY VALENTINA PIPPIA (a), ROBERTA MONTISCI (a), FEDERICA SANCASSIANI (b), MICHELA CONGIA (a), ROBERTO FLORIS (a), MANUELA CHERCHI (b), ANGELA MARIA SANNA (b), MASSIMO RUSCAZIO (a), LUIGI MELONI (a) (a) CLINICA CARDIOLOGICA, OSPEDALE SAN GIOVANNI DI DIO, UNIVERSITÀ DEGLI STUDI DI CAGLIARI; (b) CONSULTATION PSYCHIATRY AND PSYCHOSOMATIC UNIT, CAGLIARI Purpose. During acute ST-elevation myocardial infarction (STEMI) early myocardial reperfusion is the target therapy to salvage ischemic myocardium. Integrated STEMI-network reduces in-hospital delay, but addresses only a part of the overall delay to reperfusion therapy. Thus, educational campaigns to raise awareness in the presence of suspicious symptoms for STEMI have failed to reduce the patients delay in decision-making. Alexithymia (AL) is a condition characterized by the inability to perceive, recognize and describe the emotional states. The aim of our study was to assess the role of AL on delay in seeking medical care and on total ischemic time (TIT) among STEMI patients. Methods. Ninety-five STEMI patients referred by the Emergency Medical Service (EMS) to our department for primary PCI, mean age 60.8±11.5 yrs form the study population. Socio-demographic and clinical characteristics, cognitive and emotional factors, AL (Toronto Alexithymia scale-20 item, TAS-20) were evaluated. Time to presentation (TTP), first medical contact-to-balloon (FMCTB), door-to-balloon (DTB) and TIT data were also collected. Results. According to the TAS-20, we identified 27 patients with high AL ( AL group, AG) and 68 patients with low AL score (group no AL, No-AG). The two groups did not differ in age (mean age 64.3±11.9 vs 59.5±11.2,p=0.08), but in the AG mostly were female (37% vs 15%, p = 0.016) and AG also showed a lower level of education (92.6% vs. 55.2%, p = 0.001). TTP (258.5 min vs 139 min, p=0.0001), FMCTB ( 101 min vs 78.5 min,p=0.03) were significantly longer in AG than No-AG, but no difference was found in DTB (50 min vs 40 min, p=0.99). Moreover, AG patients showed a longer TIT than No-AG patients (258.5 min vs 139, p=0.0001). At Multi-variable analysis AL was the only independent determinant of a TIT>120 min (p=0.037). Conclusions. Our data showed that AL contributes to the pre-hospital delay to reperfusion in STEMI patients, especially in women. These preliminary results address the need to act on psychological factors to improve the patient's perception of symptoms, in order to reduce the TIT in the presence of an efficient integrated STEMI-network 6

7 O7 RUOLO PROGNOSTICO DEL TRAP-TEST NELLO STUDIO DELLA REATTIVITA' PIASTRINICA IN PAZIENTI SOTTOPOSTI AD ANGIOPLASTICA CORONARICA PERCUTANEA. SOTTOSTUDIO PRODIGY. SILVIA PUNZETTI (A), RITA PAVASINI (A), SIMONE BISCAGLIA (A), GIANLUCA CAMPO (A), CLAUDIO CECONI (A) (A) U.O. CARDIOLOGIA, AZIENDA OSPEDALIERA UNIVERSITARIA DI FERRARA - FERRARA INTRODUZIONE: Una spiccata reattività piastrinica (RP) è correlata ad un rischio aumentato di eventi ischemici, come già dimostrato in numerosi studi; infatti la RP residua in pazienti in terapia con clopidogrel è strettamente correlata agli ischemici e complicanze emorragiche in pazienti trattati con angioplastica coronarica percutanea (PCI). Il Multiplate Analyzer (Verum Diagnostica, Monaco, Germania) è uno strumento in grado di saggiare, attraverso l uso di diversi agonisti piastrinici, le differenti vie di attivazione piastrinica. Il suo TRAPtest (thrombin receptor activating peptide, TRAP), finora scarsamente utilizzato, riveste un potenziale vantaggio in quanto in grado di determinare l intera attività piastrinica, non essendo vincolato in modo selettivo agli agenti antipiastrinici (ad esempio acido arachidonico - aspirina o adenosina difosfato - clopidogrel). OBIETTIVO: Determinare il ruolo prognostico del TRAPtest in pazienti con cardiopatia ischemica trattati con PCI. METODI: Sono stati arruolati, in uno studio monocentrico prospettico, 715 pazienti con cardiopatia ischemica trattati con PCI. I pazienti arruolati erano randomizzati a ricevere la duplice terapia antiaggregante (aspirina+clopidogrel) per 6 o 24 mesi. Durante PCI è stata valutata la RP tramite TRAPtest. I dati clinici, angiografici e di RP sono stati correlati con l incidenza di eventi avversi ischemici ed emorragici a 2 anni. RISULTATI: I valori del TRAPtest non erano distribuiti secondo una curva di normalità (p<0.001), e risultavano significativamente maggiori nei pazienti con ridotta clearance della creatinina (<60 ml/min) (1231 [ ] vs [ ], p=0.02, rispettivamente) e nei pazienti con diagnosi di infarto miocardico con sopraslivellamento del tratto ST (STEMI) (1265 [ ] vs [ ], p=0.04, rispettivamente). Dall analisi multivariata è emerso che, la clearance della creatinina (HR: 0.98, 95%, CI: , p=0.03), la frazione di eiezione ventricolare sinistra (HR: 0.97, 95% CI: , p=0.04) ed il ricovero per STEMI (HR: 3, 95%, CI: 1.2-7, p=0.04) rappresentavano fattori predittivi indipendenti di outcome. I valori di TRAPtest, inoltre, non risultavano correlati con l incidenza a due anni di morte, infarto miocardico ed eventi cerebrovascolari (endpoint primario), o con le complicanze emorragiche. Analizzando invece i pazienti che erano stati trattati con aspirina+clopidogrel per 6 mesi, si osservava che l occorrenza dell endpoint primario era significativamente superiore nei pazienti con TRAPtest sopra la mediana (18% vs. 10,5%, p = 0.04, rispettivamente per un significativo aumento degli eventi avversi dopo la sospensione del clopidogrel al 6 mese. (p=0.02) Dall' analisi multivariata è emerso come il TRAPtest rappresenti un fattore predittivo indipendente di complicanze ischemiche a 2 anni (HR: 1.8, 95%CI: , p=0.04). Lo stesso invece non risultava valido per gli eventi emorragici e per i pazienti randomizzati a 24 mesi di aspirina + clopidogrel. CONCLUSIONI: I valori di RP non predicono l occorrenza di eventi avversi ischemici o emorragici, ma dopo la sospensione del clopidogrel, essi son in grado di stimare un aumento delle complicanze ischemiche nei pazienti in duplice terapia antiaggregante della durata di 6 mesi. 7

8 O8 PROGNOSTIC IMPACT OF BNP VARIATIONS IN PATIENTS ADMITTED FOR ACUTE DECOMPENSATED HEART FAILURE WITH IN-HOSPITAL WORSENING RENAL FUNCTION. DAVIDE STOLFO (A), ELISABETTA STENNER (B), MARCO MERLO (A), ANDREA GIUSEPPE PORTO (A), CRISTINA MORAS (A), GIULIA BARBATI (A), ANETA ALEKSOVA (A), ALESSANDRA BUIATTI (A), GIANFRANCO SINAGRA (A) (A) S.C. CARDIOLOGIA AZIENDA OSPEDALIERO-UNIVERSITARIA OSPEDALI RIUNITI DI TRIESTE; (B) LABORATORY MEDICINE DEPARTMENT, AZIENDA OSPEDALIERO-UNIVERSITARIA, OSPEDALI RIUNITI DI TRIESTE Objectives. Worsening renal function (WRF) during hospitalization is frequent in patients admitted for acute decompensated heart failure (ADHF), but its prognostic impact is still debated. BNP inhospital trends may be helpful in order to estimate the congestive state of patients with ADHF. We hypothesized that changes in BNP might identify patients with optimal diuretic responsiveness resulting in transient WRF, not negatively affecting the prognosis. Methods and Results. 122 patients admitted for ADHF were prospectively included. BNP and egfr were evaluated at admission and discharge. A 20% relative decrease in egfr defined WRF, whereas a BNP reduction 40% was considered significant. WRF occurred in 28 (23%) patients. Higher variation in urea and hemoconcentration were more likely in these patients. There were no differences in the primary outcome between patients with and without WRF (43 vs. 45%, p=0.597). A significant reduction in BNP over the hospitalization occurred in 59% of the overall population and 71% of patients with WRF. At a median follow-up of 13.0 (IQR 6 36) months, WRF patients with significant BNP reduction had a lower rate of death/urgent heart transplantation/re-hospitalization if compared with WRF patients without BNP reduction (30 and 75%, respectively; p=0.007). Favourable BNP trends independently predicted the outcome both in the overall population (HR 0.301, 95% CI , p<0.001), and WRF patients (HR 0.222, 95% CI , p=0.016). Conclusions. WRF is not associated with a worst prognosis in ADHF. When associated with a significant BNP in-hospital reduction, WRF identifies patients with adequate decongestion at discharge and favourable outcome. 8

9 O9 MYOCARDIAL VENTRICULAR ADAPTATION TO PULMONARY HYPERTENSION IN NON-ISCHEMIC DILATED CARDIOMYOPATHY: A STUDY PERFORMED BY CARDIAC MAGNETIC RESONANCE Roberta Ancona (a), Salvatore Comenale Pinto (a), Pio Caso (a), Fortunato Arenga (a), Maria Gabriella Coppola (a), Raffaele Calabrò (a) (a) Non invasive Cardiology, Chair of Cardiology, Department of Cardiology, Second University of Naples MANUEL DE LAZZARI (a), MARTINA PERAZZOLO MARRA (a), ALBERTO CIPRIANI (a), FILIPPO ZILIO (a), ANGELA SUSANA (a), VERONICA SPADOTTO (a), ANNACHIARA FRIGO (a), BENEDETTA GIORGI (b), GIUSEPPE TARANTINI (a), FRANCESCO TONA (a), CRISTINA BASSO (a), RENATO RAZZOLINI (a), SABINO ILICETO (a) (a) DEPARTMENT OF CARDIAC, THORACIC AND VASCULAR SCIENCES, UNIVERSITY OF PADUA; (b) INSTITUTE OF RADIOLOGY, UNIVERSITY OF PADUA Background: The presence of pulmonary hypertension (PH) is a well-established prognostic factor in heart failure (HF) in terms of increased mortality and hospitalization rates. The potent prognostic impact of PH in HF suggests an important role for pre-clinical detection of signs indicating an ongoing RV dysfunction due to its remodeling. Recently, several studies have highlighted the potential utility of cardiac magnetic resonance (CMR) in patients with arterial pulmonary hypertension (PAH) after discovering the presence of late gadolinium enhancement (LGE) in the RV junctional insertion point of the interventricular septum in the majority of these patients. Purposes: the aims of our study were: 1) to evaluate the presence and the prevalence of RV-LV junctional LGE in patient with NIDC, 2) to evaluate the possible relationship between LGE and hemodynamics obtained by a simultaneously right side catheterization, and 3) to evaluate the prognostic significance of this pattern in terms of major events and specific heart failure outcome. Methods: The study population included a consecutive series of patients with diagnosis of NIDC. To be enrolled, patients had to have a depressed LV systolic function (LV EF <50%), absence of flowlimiting coronary artery disease. Exclusion criteria were: recent onset of heart failure (<1 month) and contraindication to CMR. Diagnostic right heart catherization was performed in all patients. During follow up the events collected were: hospitalization for decompensated heart failure, cardiac death or heart transplantation and ventricular arrhythmias. Results: 118 patients fulfilling the enrollment criteria. On post-contrast sequences, 38 (32%) showed junctional LGE: in 29/38 patients, junctional LGE was associated with mid-wall interventricular septal stria, in 8/38 patients LGE was confined only to the junctions points, and one patient had junctional LGE associated with mid-wall stria on lateral free LV wall. In the junctional LGE group, the patients had increased RV EDV (97 vs 90 ml/m 2, p=0.03) and reduced RV EF (52 vs 57%; p<0.01). Patients with junctional LGE showed a worse hemodynamic profile in terms of pulmonary hypertension (61 vs 39%; p=0.027) and LVEDP (74 vs 55%; p=0.019); moreover, this group showed an increased value of PCWP (55 vs 33%; p=0.018) with a mean value of 20 mmhg indicating a postcapillary pulmonary hypertension. During a median follow-up of 37 months Kaplan-Meier analysis revealed a significant correlation between the junctional LGE presence and occurrence of episodes of HF (p=0.03). On univariate Cox regression analysis, all right catheterization parameters indicating a worse hemodynamics, including RV dysfunction/ dilation were associated with junctional LGE. On multivariable analysis, only the increased LVEDP showed a trend for prediction of heart failure (HR 2.8; 95% CI , P= 0.079). Conclusions: in this study we demonstrated that the presence of junctional LGE in the RV insertion points is a frequent CMR finding in NIDC, up to 32% in our population. The strictly relationship with 9

10 all hemodynamic parameters indicating the presence of PH complicating the NIDC with junctional LGE makes this peculiar CMR pattern not specific for pre-capillary PH as herein demonstrated. Finally, the junctional LGE pattern on follow-up was able in our study to identify the patients at risk for developing HF, so assuming the role of an imaging marker of ventricular remodeling in patients with NIDC complicated by PH. O10 DOXORUBICIN IMPAIRS THE INSULIN-LIKE GROWTH FACTOR-1 AXIS IN H9C2 CELLS PIETRO AMERI (A), PATRIZIA FABBI (A), PAOLO SPALLAROSSA (A), CHIARA BARISIONE (A), SILVANO GARIBALDI (A), PAOLA ALTIERI (A), BARBARA REBESCO (B), MARCO CANEPA (A), GIORGIO GHIGLIOTTI (A), CLAUDIO BRUNELLI (A) (A) CARDIOLOGY UNIT, DEPARTMENT OF INTERNAL MEDICINE, UNIVERSITY OF GENOVA; (B) ANTIBLASTIC DRUG UNIT, AOU-IRCCS SAN MARTINO IST Background and aims: Depletion of cardiac progenitor cells (CPCs) is central of to the pathogenesis of chronic anthracycline cardiotoxicity. Insulin-like growth factor-1 (IGF-1) promotes the survival of CPCs by activating type 1 IGF receptor (IGF-1R). Within the myocardium, IGF-1 action is modulated by IGF binding protein-3 (IGFBP-3), which sequesters IGF-1 away from IGF-1R. Here, we investigated the effect of doxorubicin on the IGF-1 system in the H9c2 cell model of cardiomyocytes with proliferative and differentiative potential. Results: At concentrations comparable to those observed in patients after bolus infusion (0.1-1 µm), doxorubicin dose-dependently caused apoptosis of H9c2 cells. Exposure to the drug also resulted in a dose-dependent decrease in IGF-1R levels (Figure, panels A and B). By contrast, IGFBP-3 expression increased (panels A and C). While IGF-1 was still capable to rescue H9c2 cardiomyocytes from apoptosis triggered by 0.1 µm doxorubicin (panel D), it was no longer effective in the presence of 1 µm doxorubicin (panel E). Consistent with previous reports, doxorubicin also dose-dependently induced p53, which represses the transcription of IGF1R and induces the one of IGFBP3. Pretreatment with the p53 inhibitor, pifithrin-alpha (PFT-α), prevented the changes in IGF-1R and IGFBP-3 in response to doxorubicin, suggesting that they were mediated by p53. Moreover, PFT-α counteracted apoptosis initiated by doxorubicin. Of note, the decrease in IGF-1R and the increase in IGFBP-3, as well as apoptosis, were also antagonized by pre-treatment with the antioxidant agents, N-acetylcysteine, dexrazoxane, and carvedilol. Conclusions: Doxorubicin down-regulates IGF-1R and up-regulates IGFBP-3 via p53 in H9c2 cells. This translates into a relative resistance to IGF-1 pro-survival activity that may contribute to apoptosis. Further studies are needed to confirm our findings in human CPCs and explore the possibility of manipulating the IGF-1 axis to protect against anthracycline cardiotoxicity. 10

11 CARDIOLOGIA INTERVENTISTICA - TAVI O11 ADDITIONAL TOOL TO ASSESS HEMODYNAMIC IMPROVEMENT AFTER TRANSCATHETER AORTIC VALVE IMPLANTATION: ECHO-DOPPLER STUDY OF THE CEREBRAL BLOOD FLOW ANDREA ANCESCHI (A), SAVERIO MUSCOLI (A), VALERIA CAMMALLERI (A), DOROTEA RUBINO (A), FRANCESCA DE PERSIS (A), MASSIMILIANO MACRINI (A), MASSIMO MARCHEI (A), ERSILIA MAZZOTTA (A), GIUSEPPINA PASCUZZO (A), EUGENIA MAIO (A), GIAN PAOLO USSIA (A), FRANCESCO ROMEO (A) (A) TOR VERGATA DIPARTIMENTO DI CARDIOLOGIA Purpose: Aim of our study was to evaluate the arterial cerebral blood flow variation after transcatheter aortic valve implantation (TAVI). Methods: The study includes 56 patients who underwent TAVI for severe aortic stenosis (93%), pure aortic insufficiency (2%) and surgical bioprosthesis degeneration (5%) from June 2013 to June 2014: mean age 83.73±0.63year-old; trans-aortic velocity max 4.28±0.16 m/sec; mean gradient 49.59±2.75 mmhg; left ventricular ejection fraction 49.58±1.61%. Patients with significant stenosis of the left common and internal carotid arteries (LICA) and previous endoarterectomy were excluded. Internal diameter of the LICA was measured at baseline (0.73±0.08 cm); blood flow (BF), systolic peak velocity (spv) and mean acceleration time (mat) were recorded as parameters of cerebral blood flow. Diastolic and systolic systemic pressure and heart rate were monitored during the procedure. All parameters were recorded at baseline, after balloon aortic valvuloplasty (BAV), and within 10 minutes after the device release. Results: All procedures were performed in standard fashion using the transfemoral approach in 54 patients and left distal transaxillary route in 3 patient. The device success was 98%, 3 patients needed acute valve-in-valve therapy for prosthesis malposition. The mean procedural and revalving time were 55.69±2.68 and 5.54±1.07minutes, respectively. No intraprocedural death or major adverse events occurred. Collected echo-doppler data showed a significant improvement of the cerebral blood flow after BAV and, subsequentially, after final release of the valve when compared to baseline. No 11

12 statistically significant differences of systolic and diastolic pressure, and heart rate, were observed after the procedure (Table 1). Conclusions: Non invasive monitoring of echo-doppler measurements (namely BF, spv and mat), may be an useful additional tool to assess the hemodynamic improvement after TAVI, specifically for the cerebral arterial district. O12 COMPARISON BETWEEN 957 SELF-EXPANDABLE AND 947 BALLOON- EXPANDABLE VALVES FOR PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE IMPLANTATION: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS AND ADJUSTED OBSERVATIONAL RESULTS FRANCESCA GIORDANA (A), FABRIZIO D ASCENZO (A), CLAUDIO MORETTI (A), FEDERICO CONROTTO (C), MAURIZIO D AMICO (C), STEFANO SALIZZONI (B), MICHELE LA TORRE (B), MAURO RINALDI (B), SEBASTIANO MARRA (C), FIORENZO GAITA (A) (A) DIVISION OF CARDIOLOGY, CITTÀ DELLA SALUTE E DELLA SCIENZA, UNIVERSITY OF TURIN, TURIN, ITALY; (B) DIVISION OF CARDIO-SURGERY, CITTÀ DELLA SALUTE E DELLA SCIENZA, UNIVERSITY OF TURIN, TURIN, ITALY; (C) DIVISION OF CARDIOLOGY, CITTÀ DELLA SALUTE E DELLA SCIENZA, TURIN, ITALY Introduction. Two different devices, self- and balloon- expandable, have been developed for patients undergoing transcatheter aortic valve implantation (TAVI), although contrasting data are reported about their efficacy and safety. Methods. Pubmed, Medline and Google Scholar were systematically searched for studies comparing balloon expandable and self-expandable TAVI devices, with data derived from randomized controlled trial or multivariate analysis. All cause death at 30-days and at follow up were the primary end points, while post procedural moderate or severe aortic regurgitation, stroke, major vascular complications, bleeding and pacemaker implantation the secondary ones. Results. Six studies with 957 self-expandable and 947 balloon-expandable valves were included, one randomized controlled trial and five observational study. Median age was 82 (81-83) years, with a logistic EuroSCORE of 22% (21-22%); 50% (44-51%) of them were implanted with a 26 mm prosthesis. At 30-days, the rate of death (OR 1.02 [0.94, 1.11]) and stroke (OR 1.23 [0.89, 1.69]) did not significantly differ between the two valves. The self-expandable prosthesis has a lower rate of major or life threatening bleeding (OR 0.86 [0.81, 0.91]) and major vascular complications (OR 0.88 [0.82, 0.94]), while the rate of PM implantation (OR 1.74 [1.45, 2.09]) and of moderate or severe aortic regurgitation (OR 1.35 [1.18, 1.55]) was higher. After a follow up of 360 days ( ), the rate of all cause death did not significantly differ between the two groups (OR 1.00 [0.93, 1.08]). At the meta-regression analysis, the benefit of balloon expandable valves has increased with annulus diameter (beta 0.15, p<0.001). Conclusions. The risk of moderate or severe aortic regurgitation and pace maker implantation was lower in the balloon expandable devices, although with a more frequent rates of vascular and bleeding complications. The between groups all cause of death at 30 and 360 days did not significantly differ. 12

13 O13 EXPANDABLE SHEATH FOR TRANSFEMORAL TRANSCATHETER AORTIC VALVE REPLACEMENT: PROCEDURAL OUTCOMES AND COMPLICATIONS PAOLA ANGELA MARIA PURITA (A), ELISA COVOLO (A), MICHELA FACCHIN (A), MARTA MARTIN (A), ERMELA YZERAJ (A), ROSARIA TENAGLIA (A), FILIPPO ZILIO (A), AHMED AL MAMARY (A), MARCO MOJOLI (A), GIANPIERO D AMICO (A), ALBERTO BARIOLI (A), GILBERTO DARIOL (A), BLERI CELMETA (A), VALERIA GASPARETTO (A), CHIARA FRACCARO (A), DEMETRIO PITTARELLO (B), GIAMBATTISTA ISABELLA (A), GIUSEPPE TARANTINI (A), MASSIMO NAPODANO (A) (A) DEPARTMENT OF CARDIAC, THORACIC AND VASCULAR SCIENCES, UNIVERSITY OF PADUA; (B) ANESTHESIOLOGY DEPARTMENT, UNIVERSITY OF PADUA Aims: Among transfemoral Edwards transcatheter aortic valve implantation (TF TAVI), the expandable sheath (e-sheath) has been described to present a lower rate of access complications, compared to the fixed size sheath (f-sheath). Our aim was to compare the incidence of periprocedural complications when using f-sheath vs. e-sheath during TAVI. Methods: From September 2009 to May 2014, we included 141patients undergoing TF TAVI in our center with the Edwards SAPIEN( ) /SAPIEN XT/ SAPIEN 3 balloon-expandable prosthesis (Edwards Lifesciences Irvine, CA) utilizing the Novaflex, Novaflex+ and Commander delivery systems; access closure was obtained with the Prostar system in all cases. E-sheath (18/19/16/14 F) was used in 91 patients (64,5%), whereas f-sheath (18/19 F) was utilized in 50 patients. The crossover technique was performed in 108 patients (79,4%). All complications were defined according to Valvular Academic Research Consortium 2 (VARC-2) consensus. Results: Out of 305 patients who underwent TAVI, 76 (54,7%) was female, mean age was 80.5 ± 6.5 years and logistic EuroSCORE was 20.7% ± Mean minimal femoral artery diameter was 6.9 ± 1.4 in e-sheath group and 7.4± 0.8 mm f-sheath group, p Mean outer diameter was 6.9 ± 0.4 in e-sheath and 7.4 ± 0.1 in f-sheath group, p< Outer sheath diameter/artery ratio was ± in e-sheath group and 1.10 ± in f-sheath group, p 0.4. VARC major vascular complications rate were similar in the 2 groups: e- sheath 14 (15.6%) vs. f-sheath 6 (12.2%), p 0.62, as well as minor vascular complications: 28 (31.5%) vs. 14 (29.2%), p Similarly, bleeding complications were comparable between e-sheath and f-sheath groups: life-threatening bleeding 2 (4.2%) vs. 2 (2.2%), major bleeding 19 (21.3%) vs. 13 (27.9%), and minor bleeding 29 (32.3%) vs. 9 (18.8%), p By logistic regression analysis, no association was found between vascular complication and sheath type, outer, minimal lumen diameter, or ratio of out of diameter to minimal lumen ratio. Conclusions: The use of expandable sheath did not reduce vascular and bleeding complications in TF-TAVI. However the introduction of this approach allowed transfemoral TAVI in patients with smaller femoral arteries (figure) probably limiting its potential benefits. 13

14 O14 LONG TERM FOLLOW-UP OF PATIENTS UNDERGOING VALVULOPLASTY IN TAVI ERA: A MULTICENTRIC RETROSPECTIVE STUDY CLAUDIO MORETTI (A), LUDOVICA MARANGONI (A), ILARIA MEYNET (A), SARA RETTEGNO (A), FABRIZIO D ASCENZO (A), MAURIZIO D AMICO (A), STEFANO SALIZZONI (A), SEBASTIANO MARRA (A), FIORENZO GAITA (A) (A) DIPARTIMENTO DI CARDIOLOGIA. A.O.U. CITTA DELLA SALUTE E DELLA SCIENZA TORINO Aims: The introduction of transcatheter aortic valve implantation (TAVI) has generated a renewed interest in the treatment of high risk patients with severe aortic stenosis and serious contraindication for aortic valve replacement. This study describes the indications and long-term outcomes of ballon aortic valvuloplasty (BAV) in recent years. Methods: All patients undergoing BAV in our centres from 2005 to 2013 were enrolled. All cause death at follow-up were the primary end-point, while need of re-intervention, myocardical infarction and stroke the secondary ones, along with BAV periprocedural complications according to VARC criteria (death, bleeding, vascular complications, acute kidney injury) Results: Among 586 consecutive patients, BAV as bridge to TAVI was performed in 277, (47,3%), as bridge to surgical aortic valve replacement (SAVR) in 71 (12,1%) and as destination therapy in 238 (40,6%).Median age was of 82,1± 7,4,54,1% of them being female, with a median ejection fraction of48,3%±15,8. In hospital mortality was 8,5%,5,2% after excluding patients presenting with cardiogenic shock, being acute kidney injury (10,7%) the most frequent complication. cardiogenic shock and a renal clearance below 60ml/min/m2 were independent predictors of all cause death in a multivariate analysis. After a median follow-up of 240 days, 31,4% of patients, died, 5,6% were rehospitalized for heart failure and 33,8% performed a new intervention (10,1% BAV, 71,2%TAVI, 18,7% SAVR) Echocardiography showed that the medium and peak transaortic gradients decreased after valvuloplasty from 46mmHg(IC 44,3-48,2) to 39mmHg (IC 37,8-44), and from 78mmHg(IC 74,8-81,5) to 59mmHg (53-64) respectively. After 6 months medium gradient was 36mmHg (IC 28,7-38,1)and peak gradient 54mmHg (IC 46,4-62,9), showing durability of the valvuloplasty. Aortic valve area (AVA) increased after valvuloplasty from 0,67cm2 (IC 0,64-0,69) to 1,50 cm2 (IC 1-1,9) and 0.95 cm2 (IC0.8-1) after 6 months Conclusion: BAV is nowadays safe and effective, with a durable effect in the reduction of transaortic valve gradient. Clinically, after 10 months follow up, no reintervention is needed in most of the patients O15 CLINICAL OUTCOME OF PATIENTS WITH AORTIC STENOSIS AND CORONARY ARTERY DISEASE UNDERGOING INCOMPLETE TREATMENT STRATEGIES GIUSEPPE DI GIOIA (A, B), MARIANO PELLICANO (A), ANGELA FERRARA (A), GABOR TOTH (A), JULIEN ADJEDJ (A), WILLIAM WIJNS (A), IVAN DEGRIECK (A), FILIP CASSELMAN (A), BERNARD DE BRUYNE (A), BRUNO TRIMARCO (B), EMANUELE BARBATO (A, B) (A) CARDIOVASCULAR CENTER AALST, OLV HOSPITAL, AALST (BELGIUM); (B) UNIVERSITÀ DEGLI STUDI DI NAPOLI FEDERICO II. DIPARTIMENTO DI SCIENZE BIOMEDICHE AVANZATE Purpose: Current guidelines recommend aortic valve replacement (AVR) with coronary artery bypass graft (CABG) in patients with moderate-to-severe aortic stenosis and significant coronary 14

15 artery lesions. In real world, this is not always feasible due to advanced age and comorbidities. We sought to evaluate the clinical outcome of patients treated not according to recommendations. Methods: From 2002 to 2010, we retrospectively included 650 patients with moderate to severe aortic stenosis and at least one significant coronary lesion (diameter stenosis>50%): 149 (23%) were treated with medical therapy only (Gr 1), 107 (17%) with percutaneous coronary intervention (PCI) (Gr 2), 74 (11%) with AVR (Gr 3), and 320 (49%) with combined CABG and AVR (Gr 4). Primary endpoint of the study was overall death up to 5 years. Results: Patients characteristics like logistic euroscore (Gr 1: 18±13 vs. Gr 2: 15±15 vs. Gr 3: 16±14 vs. Gr 4: 11±10, p <0.01) and rate of severe aortic stenosis (Gr 1, 115 [77%] vs. Gr. 2, 57 [53%] vs. Gr 3, 72 [97%] vs. Gr 4, 292 [91%], p <0.01) were significantly different among the 4 groups. At a median follow-up of 59 months, overall death significantly decreased along the groups (Gr 1, 101 [68%] vs. Gr 2, 47 [44%] vs. Gr 3, 25 [34%] vs. Gr 4, 74 [23%], p <0.01) (see figure). Compared to Gr 1, Cox-regression analysis adjusted for potential confounders showed a significant decrease in the risk of death of Gr 2 (HR: 0.61 [ ], p <0.01), Gr 3 (HR: 0,59 [ ], p <0.01) and Gr 4 (HR: 0.63 [ ], p <0.01). Conclusions: In patients with aortic stenosis and at least one significant coronary lesion, we confirm that medical therapy only is associated with the worst clinical outcome. Our data suggest that when combined CABG/AVR is not feasible, PCI or AVR alone significantly improve long-term survival. O16 PROTECTIVE IMPACT OF PRE-EXISTENT AORTIC REGURGITATION IN TAVI PATIENTS DEVELOPING POST PROCEDURAL PARAVALVULAR LEAK MICHELA FACCHIN (A), AUGUSTO D ONOFRIO (A), ANDREA COLLI (A), ELISA COVOLO (A), PAOLA ANGELA MARIA PURITA (A), MARTA MARTIN (A), ERMELA YZEIRAY (A), MARCO MOJOLI (A), BLERI CELMETA (A), ALBERTO BARIOLI (A), GIANPIERO D AMICO (A), FILIPPO ZILIO (A), GILBERTO DARIOL (A), AHMED AL-MAMARY (A), VALERIA GASPARETTO (A), CHIARA FRACCARO (A), DEMETRIO PITTARELLO (A), MASSIMO NAPODANO (A), GIAMBATTISTA ISABELLA (A), SABINO ILICETO (A), GIUSEPPE TARANTINI (A) (A) DEPARTMENT OF CARDIAC, THORACIC AND VASCULAR SCIENCES, UNIVERSITY OF PADUA Background: Even if trans-catheter aortic valve implantation (TAVI) is a safe and effective technique in high-risk symptomatic severe aortic stenosis (SSAS) patients, the evidence of post procedural paravalvular leak is common and it is associated with worse outcome. Aim: we investigated the impact of pre-existent aortic regurgitation (AR) on cardiovascular mortality in SSAS patients treated with TAVI, based on the degree of post-procedural paravalvular leak. Methods: we prospectively evaluated the cardiovascular mortality in patients affected by SSAS undergoing TAVI in our department between March 2009 to May 2014 with balloon-expandable aortic valve (Edwars Sapien, Edwards Sapien XT and Edwards Sapien 3, Edwards Lifesciences Irvine, CA). The presence and the degree of pre-procedural AR and PVL were assessed by Dopplermeasurements and stratified as absent (0/3), mild (1/3), and moderate/relevant ( 2/3). Results: our study population included 243 consecutive patients with a mean age 80±6.7 years, 53% were female, Euroscore logistic/ii were 20±12/9±7, basal end diastolic volume of left ventricular (LV) was 63 ml/mq and LV ejection fraction was 60%±12. The access was trans-femoral in 56.7%, trans-apical in 40.8%, trans-subclavian in 0.4% and trans-aortic in 2% of patients. Seventy patients (28.8%) had not baseline AR, 113 (46.5%) had a mild AR and 60 (24,7%) moderate/relevant AR. After aortic valve implantation 139 patients (58.6%) did not show PVL, 84 (35.5%) had a mild PVL and 14 (5.9%) had a moderate PVL. The Kaplan Meier analysis showed the presence of any grade of 15

16 PVL was associated with an increase of cardiovascular mortality only in the patient without a preexisting AR (p=0.05) (see figure). Conclusions: our findings seem to suggest a protective value on cardiovascular mortality of any grade of the pre-existing AR in patients that developed a post-procedural moderate or relevant PVL. IPERTENSIONE POLMONARE - 1 O17 EFFECTS OF MEDICAL TREATMENT FOR OPERABLE AND INOPERABILE CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION PATIENTS ANDREA RINALDI (A), CRISTINA BACHETTI (A), FABIO DARDI (A), ENRICO GOTTI (A), GAIA MAZZANTI (A), ALESSANDRA ALBINI (A), ENRICO MONTI (A), CLAUDIA BERNABÉ (A), ELISA ZUFFA (A), CAROLINA BARBERI (A), RACHELE BIONDI (A), MARGHERITA TIEZZI (A), MASSIMILIANO PALAZZINI (A), ALESSANDRA MANES (A), NAZZARENO GALIÉ (A) (A) DEPARTMENT OF SPECIALIZED, DIAGNOSTIC AND EXPERIMENTAL MEDICINE UNIVERSITY OF BOLOGNA - ITALY Background: Pulmonary endoarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH); specific PAH drugs therapy may improve hemodynamics and exercise capacity in operable and inoperable patients. Purpose: to assess effects of targeted PAH drugs in CTEPH patients. Methods: between July 2003 and October 2013, 123 patients (mean age 65±16 years) with inoperable CTEPH and 69 patients (mean age 57±16 years) with operable CTEPH received PAH specific drugs. Six-minute walk test (6MWT) and right-heart catheterization data were collected at baseline and after 3-4 months of therapy in inoperable patients and at baseline, immediately before PEA and 6 months after PEA in operated patients. Results: In inoperable group 61 patients received phosphodiesterase type-5 inhibitors (PDE5-I), 36 endothelin receptor antagonists (ERA), 5 prostanoids and 21 combination therapy (CT); in operable group 38 patients received PDE5-I, 21 ERA and 10 CT. In inoperable group targeted PAH drugs reduced mean pulmonary arterial pressure (mpap) from 48±11 to 44±11 (p<0.0001), pulmonary vascular resistance (PVR) from 9.9±4.9 to 7.4±3.3 WU (p<0.001) and increased cardiac index (CI) from 2.4±0.7 to 2.8±0.8 l/min/m² (p<0.001) and 6MWT from 360±137 to 419±129 m (p<0.001). In operable group targeted PAH drugs reduced mpap from 50±10 to 45±9 (p<0.001), PVR from 9.8±3.8 to 7.6±3.0 WU (p<0.001) and increased CI from 2.5±0.6 to 2.8±0.7 l/min/m² (p<0.0002) and 6MWT from 394±135 to 442±127 m (p<0.001). After PEA mpap decreased from 45±9 to 27±9 mmhg (p<0.001), PVR decreased from 7.6±3.0 to 3.7±1.9 WU (p<0.001), CI increased from 2.8±0.7 to 3.0±0.5 l/min/m² (p=0.07) and 6MWT increased from 442±127 to 484±114 m (p<0.001). Conclusions: PAH-approved drugs improve exercise capacity and hemodynamics in patients with operable and inoperable CTEPH. Improvement of hemodynamics before PEA may favorably influence surgical results in operable subjects. 16

17 O18 DETERMINANTS AND PROGNOSTIC SIGNIFICANCE OF RIGHT VENTRICULAR REVERSE REMODELING IN IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION RECEIVING SPECIFIC MEDICAL TREATMENT ROBERTO BADAGLIACCA (A), MARIO MEZZAPESA (A), MARTINA NOCIONI (A), BEATRICE PEZZUTO (A), ROBERTO POSCIA (A), FRANCESCA PESCE (A), SILVIA PAPA (A), CRISTINA GAMBARDELLA (A), FRANCESCO FEDELE (A), CARMINE DARIO VIZZA (A) (A) DIP. SCIENZE CARDIOVASCOLARI E RESPIRATORIE - SAPIENZA UNIVERSITA DI ROMA Background. Survival in idiopathic pulmonary arterial hypertension (IPAH) is strongly associated to the ability of the right ventricle (RV) to maintain its function in face of increased afterload. Cardiac remodeling characterizes the natural history of the disease, and it has been suggested that some IPAH patients receiving goal-oriented treatment could show a RV reverse remodeling (RVRR). Objectives. To determine the predictors of RVRR in IPAH patients receiving specific therapy and its impact on long-term prognosis. Methods. In 102 consecutive IPAH patients RVRR was evaluated considering the main echocardiographic parameters previously demonstrated to be prognostically relevant for risk stratification: right atrium (RA) area, left ventricular systolic eccentricity index (LV-EIs) and RV end diastolic area (RVEDA). All patients were re-evaluated after 12 months of treatment (mid-term evaluation); survivors were followed for a mean of 358 ± 236 days. The first episode of clinical worsening (CW) was taken into consideration for the analysis. Results. Twenty one patients (20%) presented CW after mid-term evaluation, and other 30 patients subsequently. In a univariate analysis, changes in RVEDA (HR 1.36, p=0.001), RA area (HR 1.5, p=0.0001) and LV-EIs (HR 2.9, p=0.0001), resulted predictors of CW. Seventeen patients (17%) showed significant changes in all 3 parameters: this was indicated as complete RVRR. At logistic regression analysis, PVR reduction at mid-term follow-up resulted as independent predictor of RVRR. Baseline cardiac index (HR 0.25, 95% CI: 0.12 to 0.51; p=0.0001), RVRR (HR 0.096, 95% CI: 0.12 to 0.76; p=0.02) and changes in WHO functional class (HR 4.79, 95% CI: 2.1 to 10.6; p=0.0001) resulted significantly predictive for CW (Chi ; p<0.0001). Patients with RVRR had a significantly better long-term prognosis (p= 0.004). The event-free survival rates were, respectively, 94% and 94% versus 65% and 43% after 1 and 2 years of follow-up from mid-term re-evaluation, in patients with and without RVRR. Conclusions. RVRR significantly influences the prognosis of IPAH patients and changes in PVR during follow-up resulted as independent predictors of RVRR. O19 PREVALENCE OF THROMBOPHILIC MUTATION IN PATIENTS WITH ACUTE PULMONARY EMBOLISM MARCO ZUIN (A), CLAUDIO PICARIELLO (A), LUCA CONTE (A), DANIELA LANZA (A), MASSIMO RINUNCINI (A), SILVIO AGGIO (A), KATIA D ELIA (A), LORIS RONCON (A) (A) SOC CARDIOLOGIA OSPEDALE DI ROVIGO Purpose: Patients with pulmonary embolism (PE) have an increased frequency of thrombophilic mutations (TMs) such as factor V Leiden G1691A (FVL), prothrombin G20210A (PT), or methylenetetrahydrofolate reductase (MTHFR). We aimed to determine the prevalences of important genetic causes of thromboembolism in a Veneto cohort. 17

18 Methods: We included 68 consecutive patients (29 male, 39 female, mean age years), diagnosed with PE in Rovigo General Hospital, Department of Cardiology, between 2006 and PE was objectively confirmed with computed tomography angiography (CTA) in all subjects. Homocysteine concentration was determined using an enzymatic assay on the Hitachi 917 analyzer (Roche Diagnostics) using reagents and calibrators from Catch, Inc. were considered subjects with Hyper-homocysteinemia (H-Hcys) those having an homocysteinemia >14 g/dl. The sample were genotyped using a multiplex Polymerase Chain Reaction with reverse line blot (mpcr/rlb) hybridization assay.collection of blood samples were performed at admission and before starting treatment. Results: Of the 68 patients, 11 (16.2%) had one or more mutations. H-Hcys was present in both patients with thrombophilic mutation (TMs) and in patients without mutation (27.2% vs 15.3%, p=ns). The frequencies, among TMs, of Factor V (FV) Leiden (FVL, G1691A), Factor II (FII G20210A), methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C were 27.2%, 9%, 81.8%, and 18.1%, respectively. All patients with FVL and FII mutations were heterozygous. For C677T, 8 patients were heterozygous and 1 homozygous, while all subjects with A1298C mutation were heterozygous. In the prevalence of the two MTHFR mutations examined there was a statistical significance (as shown in Figure 1) Only in two cases were recorded two mutations simultaneously: the first between FII and FV, while the second between MHTFR C677T and FV; in both cases were all heterozygous genotype. There was no significant correlation between family history of thrombosis and presence of a TMs. Conclusions: MTHFR C677T and A1298C mutations in PE may be an important predisposing factor in general population that needs to be tested routinely. Further studies related to cardiovascular genetics in the Italian population are needed to confirm the genetic impact on PE. Figure1. Prevalence of MHTFR mutations in the cohort. 18

19 O20 RV REMODELING PATTERN PREDICTS CLINICAL WORSENING IN IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION ROBERTO BADAGLIACCA (A), MARTINA NOCIONI (A), MARIO MEZZAPESA (A), SILVIA PAPA (A), BEATRICE PEZZUTO (A), ROBERTO POSCIA (A), FRANCESCA PESCE (A), CRISTINA GAMBARDELLA (A), FRANCESCO FEDELE (A), CARMINE DARIO VIZZA (A) (A) DIP. SCIENZE CARDIOVASCOLARI E RESPIRATORIE - SAPIENZA UNIVERSITA DI ROMA Background. Prognosis in idiopathic pulmonary arterial hypertension (IPAH) is strongly associated to right ventricular (RV) function. Objectives. The aim of this study was to investigate whether RV concentric hypertrophy might be a more favorable morphological pattern compared to eccentric hypertrophy. Methods. In 75 consecutive IPAH patients RV morphological and functional features were evaluated by echocardiography and magnetic resonance. The study population was divided into two groups by the median value of RV mass/volume (M/V) ratio (0.47), allowing the distinction between RV eccentric ( 0.47) and concentric hypertrophy (>0.47). The two groups were compared for RV remodeling and systolic function parameters, WHO class, pulmonary hemodynamics and 6-minute walk test (6MWT). Patients were followed for clinical worsening (CW). Results. Despite similar afterload, patients with eccentric hypertrophy had advanced WHO class (2.7±0.6 vs 2.4±0.5; p 0.007), worse 6MWT (394±110m vs 468±88m; p 0.002), worse remodeling and systolic function parameters [RV fractional area change (34.2±9% vs 40.1±9%; p 0.01), RVESV (107.1±48ml vs 85.5±34ml; p 0.032), RVEF (32.6±11% vs 38.3±10%, p 0.029), RV MASS (70.8±26g vs 92.7±25g; p )] compared to patients with concentric hypertrophy. By Cox regression analysis, cardiac index (B ; HR 0.145; CI 95% ; p ), pericardial effusion (B 0,957; HR 2,605; CI 95% 1,128-6,017; p 0,025), M/V ratio (B -1,349; HR 0.259; CI ; p 0.017) resulted independent predictors of CW. The rate of CW at 6-months, 1-year and 2-year follow-up was 83%, 58%, 28% vs 94%, 89%, 85% respectively in patients with eccentric compared to concentric hypertrophy. Conclusions. Concentric hypertrophy might represent a more favorable RV adaptive remodeling pattern to increased afterload in IPAH. SINDROME CORONARICA ACUTA O21 PATHOPHYSIOLOGY OF ACUTE CORONARY SYNDROME IN HIV POSITIVE PATIENTS: INSIGHT FROM VIRTUAL HISTOLOGY ANALYSIS ALESSANDRA ARMATO (A), ALESSANDRA CINQUE (A), NICOLÒ SALVI (A), ANDERA CECCACCI (A), ANTONIO FUSTO (A), NOEMI BRUNO (A), GENNARO SARDELLA (A), GABRIELLA D ETTORRE (A), MASSIMO MANCONE (A), VINCENZO VULLO (A), FRANCESCO FEDELE (A) (A) SAPIENZA UNIVERSITÀ DI ROMA Introduction and Aim of the study: Numerous reports suggest, among HIV+ patients (pts), an increased rate of acute coronary syndrome and cardiac death. However, the pathophysiologic explanation of the increased rate of major cardiovascular events (MACE) in HIV+ is unknown. The histological composition and plaque morphology represent the crucial determining factors to identify unstable lesions. Virtual Histology intravascular ultrasound (VH-IVUS) is able to identify and 19

20 quantify 4 different types of atherosclerotic plaque components: necrotic, fibrous, fibro-fatty and calcific tissue. The aim of our study is to assess coronary plaque morphology using VH-IVUS in HIV+ patients in therapy with HAART and a low risk for cardiovascular events Methods: Thirteen HIV-infected patients were enrolled from the Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences of the Sapienza University of Rome (Italy). Patients, were part of population enrolled in a previous cross-sectional study, with an indication to coronary angiography per protocol based on the evidence of coronary stenosis to a dualsource cardiac-ct. On the basis of VH-IVUS, plaque components were identified as dense calcium, necrotic core, fibro-fatty tissue, or fibrous tissue, with the cross-sectional area and percentage of total plaque area reported for each component. Such lesions were classified by means of radiofrequency analysis as one of the following: thin-cap fibro-atheroma (TnCFA), thick-cap fibro-atheroma (TkCFA), pathologic intimal thickening (PIT), fibrotic plaque (FP), or fibro-calcific plaque (FCP). Results: All the patients presented a Framingham risk score <10%. The medium age was 53.3±4.1 years. The mean duration of highly active antiretroviral therapy was 12.9±2.4 years. Virtual Histology-IVUS analysis, performed on 23 coronary plaque, showed an 87% (20/23) of TkCFA and 13% (3/23) TnCFA; no other plaque morphology was observed. All the plaque were rich in fibrous tissue and necrotic tissue with a low percent of calcium (table 1). Conclusions: Virtual Histology-IVUS analysis showed an high prevalence of unstable plaque morphology rich in necrotic tissue. HIV related plaque seems to be different from general population atherosclerotic plaque: less calcific; more necrotic and often with a thick-cap. This suggest a peculiar pathophysiological mechanisms for HIV related atherosclerosis. Our data show that this HIV+ population could be at increased risk of acute cardiovascular events independently by traditional cardiovascular risk factors. Fibrous tissue, mm ±36.8 Fibrous tissue, % 58.3±5.2 Fibro-fatty volume, mm ±11.3 Fibro-fatty volume, % 16.2±3.1 Necrotic core volume, mm ±16.5 Necrotic core volume, % 21.1±4.3 Dense Calcium volume, mm 3 5.0±3.5 Dense Calcium % 4.0±1.6 O22 FRAILTY AND END-OF-LIFE IN ACS PATIENTS: IDENTIFICATION AND PROGNOSTIC IMPACT CLAUDIO MORETTI (A), MAURIZIO BERTAINA (A), GIORGIO QUADRI (A), FABRIZIO D ASCENZO (A), SEBASTIANO MARRA (A), GIUSEPPE MONTRUCCHIO (B), MASSIMO PORTA (B), FRANCO VEGLIO (B), MARIO BO (B), CHIARA COLACI (A), VIRGINIA DE SIMONE (A), FEDERICO GIUSTO (A), MARCO DI CUIA (A), FIORENZO GAITA (A) (A) CITTÀ DELLA SALUTE E DELLA SCIENZA; DIVISION OF CARDIOLOGY ; (B) CITTÀ DELLA SALUTE E DELLA SCIENZA, DEPARTMENT OF INTERNAL MEDICINE; (C) CENTRE FOR POPULATION HEALTH SCIENCES, PRIMARY PALLIATIVE CARE RESEARCH GROUP, EDIMBURGH S UNIVERSITY, UK INTRODUCTION: The role of Frailty and End of Life (EoL) in patients with Acute Coronary Syndrome (ACS) remain to be determined. METHODS: All consecutive unselected patients admitted to the Emergency Department (ED) of two european hospital with a diagnosis of ACS during three different periods among 2011 and 2013 were included. Patients were divided according to positive or negative GSF (The Gold Standards 20