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Funding Acknowledgements Type of funding sources: None. OBJECTIVES This study aimed to describe the results of a modified sympathicotomy (uniportal VATs with stellate ganglion sparing) for cardiac sympathetic denervation (CSD) in the setting of untreatable ventricular tachycardia. BACKGROUND. CSD, in patients with refractory ventricular tachycardia (VT), is comprehensively recognized as an important treatment option for patients with structural heart disease as well as congenital inherited arrhythmia syndrome. A recent case series demostrated the feasibility of the modified technique. METHODS We consecutively enrolled 8 patients with refractory VT. Baseline demographic, medical, and surgical data as well as arrhythmia outcomes and procedural complications were evaluated. RESULTS A total of 8 patients ( 7 pts NIDCM, 1 pt IDCM with mean age:68+-8 years) were enrolled for the treatment of refractory VT with a modified CSD technique. Mean sympathicotomy length were 7.3 (SD 3) min per side. 3/8 patients underwent monolateral (LCSD) sympathicotomy due to strong adesion in the right pleural cavity. Mean follow up was 13 months (SD 6). No complication occurred during the sympathicotomy. An overall reduction in VT burden and VT number was observed after the CSD despite an in-hospital early recurrence in 3 patients. CONCLUSIONS A modified CSD (sympathicotomy T2–T5) with stellate ganglion sparing and the use of unipolar radiofrequency is feasible, effective, and safe in the setting of untreatable VT. Abstract Figure. VT trend

Background/Introduction Mitochondria are dynamic regulators of cellular metabolism and homeostasis. The dysfunction of mitochondria has long been considered a major contributor to aging and age-related diseases. The prognosis of severe heart failure is still unacceptably poor and it is urgent to establish new therapies for this critical condition. Some patients with heart failure do not respond to established multidisciplinary treatment and they are classified as “non-responders”. The outcome is especially poor for non-responders, and underlying mechanisms are largely unknown. Purpose Studies indicate mitochondrial dysfunction has causal roles for metabolic remodeling in the failing heart, but underlying mechanisms remain to be explored. This study tried to elucidate the role of Mitofusin-1 in a failing heart. Methods We examined twenty-two heart failure patients who underwent endomyocardial biopsy of intraventricular septum. Patients were classified as non-responders when their left-ventricular (LV) ejection fraction did not show more than 10% improvement at remote phase after biopsy. Fourteen patients were classified as responders, and eight as non-responders. Electron microscopy, quantitative PCR, and immunofluorescence studies were performed to explore the biological processes or molecules involved in failure to respond. In addition to studies with cardiac tissue specific knockout mice, we also conducted functional in-vitro studies with neonatal rat ventricular myocytes. Results Twenty-two patients with IDCM who underwent endomyocardial biopsy were enrolled in this study, including 14 responders and 8 non-responders. Transmission electron microscopy (EM) showed a significant reduction in mitochondrial size in cardiomyocytes of non-responders compared to responders. Quantitative PCR revealed that transcript of mitochondrial fusion protein, Mitofusin-1, was significantly reduced in non-responders. Studies with neonatal rat ventricular myocytes (NRVMs) indicated that the beta-1 adrenergic receptor-mediated signaling pathway negatively regulates Mitofusin-1 expression. Suppression of Mitofusin-1 resulted in a significant reduction in mitochondrial respiration of NRVMs. We generated left ventricular pressure overload model with thoracic aortic constriction (TAC) in cardiac specific Mitofusin-1 knockout model (c-Mfn1 KO). Systolic function was reduced in c-Mfn1 KO mice, and EM study showed an increase in dysfunctional mitochondria in the KO group subjected to TAC. Conclusions Mitofusin-1 becomes a biomarker for non-responders with heart failure. In addition, our results suggest that therapies targeting mitochondrial dynamics and homeostasis would become next generation therapy for severe heart failure patients. Funding Acknowledgement Type of funding source: None

Background Ischemic cardiomyopathy (ICM) is often associated with negative LV remodelling after myocardial infarction, sometimes resulting in impaired LV function and dilation (iDCM). 4D Flow CMR has been recently exploited to assess intracardiac hemodynamic changes in presence of LV remodelling. Purpose To quantify 4D Flow intracardiac kinetic energy (KE) and viscous energy loss (EL) and investigate their relation with LV dysfunction and remodelling. Methods Patients with prior anterior myocardial infarction underwent a CMR study with 4D Flow sequences acquisition; they were divided into ICM (n=10) and iDCM (n=10, EDV>208 ml and EF Results Both LV volume and EF significantly differ (P Conclusions 4D Flow analyses effectively mapped post-ischemic LV energetic changes, highlighting the disproportionate intraventricular EL relative to produced KE; preliminary good correlation between LV energetic changes and NT-proBNP will deserve further investigation in order to contribute to early detection of heart failure. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Italian Ministry of Health

Background Most clinical data regarding the use of sacubitril-valsartan (SV) in patients with heart failure with reduce EF (HFrEF) come from clinical trials, while observational studies in real life are scarce. Purpose To analyse the efficacy, safety and tolerability of SV in patients with HFrEF in real life. Methods An analysis of the SAVE-RLife (SV Evidence in Real Life) study was performed. This is an observational and ambispective study that included all patients with HFrEF who started SV between SEP2016 and DEC2018. Results A total of 291 patients were included in the study with a median follow-up of 326 (169; 523). Mean age 66.16±11.8, 71 were women (24.4%), 209 patients started treatment at office (71.8%) and 82 during the admission (28.2%). The main aetiologies were ischemic heart disease (51.5%) and idiopathic dilated cardiomyopathy (35.4%). Comorbidities included: 71.5% hypertensive, 55.3% dyslipidemic, 37.1% AF and 44% T2DM. Baseline treatment included 85.9% beta-blockers, 87.2% ACEI or ARA-II, 65.6% MRA and 17.5% iSGLT2. After treatment start with SV, baseline and follow-up analytical parameters such as GFR, K+ levels and NT-BNP, and echo parameters of LV reverse remodeling were evaluated (Table 1). Improvement of the functional NYHA class (Figure 1) and reduction in the incidence of hospital admission or visits to emergency room (ER) were observed. Side effects were 16.2% acute renal failure, 9.3% symptomatic hypotension, 9.7% asymptomatic hypotension and 15.9% hyperkalemia. In 31 patients (11%) the drug was discontinued, one patient due to angioedema. 7.9% of patients died during follow-up, 7 of them due to HF (2.4%). Table 1 Before SV After SV P value Analytical data GFR (ml/min) 70.25±24.95 68.27±24.62 0.008 Serum K+(mEq/L) 4.53±0.50 4.71±0.456 Predictors of clinical improvement Conclusions SV has shown to improve morbidity and mortality in patients with HFrEF by improving functional class, decreasing NT-proBNP levels and reducing admissions due to HF, without significant side effects. In our study SV improved LVEF and reverse remodeling echocardiographic parameters too.

Introduction HCMV infection is a significant viral complication in HSCTR, causing either a subclinical infection or a severe disease (systemic syndrome and localized tissue invasive disease (TID)). Pre-emptive therapy used for the management of HCMV infection and prevention of disease requires the monitoring of HCMV load in blood to start antiviral therapy after detection of a viral load threshold associated to the risk for HCMV severe infection and disease. In previous studies we observed that patients reconstituting both CD4+ and CD8+ HCMV-specific T cells are generally protected from HCMV disease. Thus, determination of specific T cells may discriminate patients lacking immunity and requiring stricter virological monitoring (negative T-cell response) from those early recovering T-cell immunity and thus not requiring antiviral interventions (positive T-cell response). Aims The aim of our work is to assess the possibility to manage HCMV infection by combined virological and immunological monitoring. The primary endpoint of this study is to compare the frequency of HCMV disease between two groups of HSCTR: in the first one, pre-emptive therapy was started according to combined virological/immunological methods; the second group consisted of an historical cohort of patients monitored with HCMV-DNA as the only guiding parameter for pre-emptive therapy. Methods We analyzed adult patients receiving allogeneic HSCT: the recipients, the donor or both had to be HCMV seropositive. Virological follow-up (HCMV-DNA determination in whole blood) was performed weekly for the first 3 months, then monthly during the first year. Immunological follow-up was performed at 1, 2, 3, 4, 6, 8, 10 and 12 months. Peripheral blood HCMV-specific T cells were determined by two assays: i) iCL (infected Cell Lysate)-ELISPOT, considering as "protective" immunity a blood count of specific T-cell ≥ 0.1/µL ii) iDC-CFC (infected Dendritic Cells-Cytokine Flow Cytometry), considering as "protective" immunity a blood count of CD4+ T-cell ≥ 1/µL and CD8+ T cells ≥ 3/µL. According to study, within the first 3 months following transplantation pre-emptive antiviral therapy was given to all patients presenting a viral load ≥30.000 copies/mL blood (severe infection). Beyond 3 months following transplantation, patients with negative T-cell response continued receiving a pre-emptive antiviral therapy as reported above. In patients with positive T-cell response confirmed by both assays ("protected" patients), antiviral therapy was deferred even if viral load would reach ≥30.000 copies/mL blood. Results We performed an analysis of 36 patients with a follow-up ≥4 months from HSCT (median follow-up 245 days, 120-397; see Table 1 for patients' characteristics). Among them, 32 HCMV-seropositive HSCTR developed HCMV infection whereas 4 HCMV-seronegative patient receiving HSCT from seropositive donors did not (nor developed specific immunity). Among the 32 HSCTR with HCMV reactivation, 13 (41%) resolved spontaneously HCMV reactivation, whereas 19 (59%) had a severe infection (11 [34%] controlled the infection after a single course of Valganciclovir therapy and the remaining 8 [25%] required multiple courses for relapsing episodes). Thirty days after HSCT, levels of total and HCMV-specific CD4+ and CD8+ T cells were significantly higher in the 13 patients spontaneously resolving the infection than in the 19 patients with severe infection. The two immunological assays were concordant in detecting time to protective immune reconstitution (median time: 177 vs 183 days for iDC and iCL-ELISPOT, respectively). HCMV-specific immune reconstitution was significantly delayed in patients with multiple infection episodes (median time: 250 days post-transplantation) vs patients with a single episode of severe infection (187 days) and patients with self-resolving infection (89 days). No patient developed HCMV severe infection after HCMV-specific immune reconstitution. Currently, no patient developed HCMV disease. Conclusion These results suggest that combined virological/immunological monitoring can be useful to identify patients not requiring strict virological controls and antiviral interventions. Disclosures No relevant conflicts of interest to declare.

S 28 EACTS Part II: Catheter based mitral interventions: The mitral going transcutaneous Tuesday, 14 October 2014

Congestive heart failure is a serious health problem in Western society. Understanding of both the basic pathophysiology and the design of rational and effective treatment of this syndrome has increased dramatically in the last ten years. However, congestive heart failure remains a highly lethal disease, which kills at a rate exceeding that of most cancers. Prevention is therefore of the utmost importance and has to come primarily from a reduction in the incidence and damage done from myocardial infarction. Improved understanding of the pathophysiology of idiopathic dilated cardiomyopathy is also needed. Through understanding of pathophysiologic principles, effective therapy based on interference with known mechanisms that are operative in the disease is now available but can be refined in the future.

Dilated cardiomyopathy and right ventricular dysplasia, although their aetiologies are unknown, are separate entities which can be recognized by endomyocardial biopsy (EMB) and differentiated from other heart muscle diseases. Biventricular EMB is the most appropriate approach for the diagnosis. Histological definition is relevant to establish prognosis and treatment and for research purposes.

Excerpt Idiopathic dilated cardiomyopathy is an increasingly common disorder, with an estimated annual incidence of 7.5 cases per 100 000 persons (1). Approximately 10 000 persons in the United Sta...