Abstract Razionale. L’amiloidosi cardiaca da transtiretina (ATTR–CM), nella sua forma ereditaria o acquisita, è una cardiomiopatia a fenotipo ipertrofico–restrittivo che porta a un‘insufficienza cardiaca progressiva causata dalla deposizione extracellulare di transtiretina. Materiali e Metodi. Presso il nostro centro abbiamo avviato un ambulatorio dedicato alla gestione dei pazienti con amiloidosi cardiaca sin dal 2019. Poiché a quel tempo in Italia non erano disponibili terapie specifiche per questa condizione, decidemmo di creare un protocollo di uso compassionevole per il farmaco tafamidis in base ai risultati dello studio registrativo di fase 3. Risultati. Dopo l‘approvazione del nostro protocollo da parte dell’azienda produttrice e del comitato etico locale, a partire da ottobre 2019 e fino a novembre 2021, sono stati selezionati n=7 pazienti con ATTR–CM i quali erano idonei ricevere il farmaco (tabella 1).Dopo 22 mesi di follow–up, un paziente è deceduto per insufficienza cardiaca avanzata e un paziente ha manifestato insufficienza cardiaca che ha richiesto il ricovero in ospedale. Al termine del nostro protocollo di uso compassionevole non sono state osservate reazioni avverse al farmaco, tutti i pazienti sopravvissuti erano in classe NYHA II e hanno potuto effettuare con successo la transizione alla prescrizione ordinaria secondo i criteri del registro di monitoraggio AIFA (tabella 2). Conclusion i. Il presente rapporto descrive in dettaglio le caratteristiche della prima coorte di pazienti in Italia sottoposta a terapia farmacologica tramite uso compassionevole per il trattamento di ATTR–CM. L‘uso compassionevole è una modalità fattibile ed efficace per avviare la cura farmacologica in pazienti selezionati in attesa dell‘approvazione ufficiale da parte degli enti regolatori, il che può essere molto importante soprattutto nelle malattie ad andamento progressivo, in cui la somministrazione precoce della terapia è fondamentale per ottenere un beneficio clinico significativo.

Abstract Funding Acknowledgements Type of funding sources: None. Background Left ventricular non-compaction (LVNC) is a rare, although underdiagnosed, cardiomyopathy deriving from the incomplete development of myocardial tissue. Its presentations range from heart failure to embolism and arrhythmic events with the latter being the most frequent cause of death. Purpose To define the incidence of arrhythmic complications in LVNC and describe the interplay between systolic dysfunction and ventricular events. Methods This is a retrospective evaluation of a prospectively-collected database including all consecutive patients with a definitive diagnosis of LVNC followed-up at the Cardiomyopathy Clinic of our institution from October 2009 to August 2022. We conducted a follow-up analyzing the possible correlation between baseline characteristics and a composite outcome of ventricular arrhythmias (sustained VT or VF), appropriate ICD interventions and sudden cardiac death (SCD). We also extracted a sample from our population with preserved LVEF and compared global longitudinal strain (GLS) in compacted and non-compacted segments. Results 44 patients (29 males, 65.9%) were enrolled in the study; 36 patients (81.8%) underwent a cardiac MRI and 34 (77.3%) resulted positive for Petersen criteria. 26 patients (59.1%) had positive echocardiographic criteria, while 18 patients (40.9%) were positive for both MRI and echocardiographic criteria. Five patients (11%) experienced an arrhythmic event during a median follow-up of 2 years (1 VT, 1 VF and 3 patients with appropriate ICD interventions). No clinical, ECG or lab predictors were found for arrhythmic events apart from a history of non-sustained or sustained ventricular arrhythmias, which was associated with a 36% increased risk of subsequent VT/VF episodes (RR 1.36; 95% CI 1.01-1.85; p=0.01). Notably, LVEF (which was ≤35% in 11% of the patients) was not able to significantly discriminate arrhythmic risk (50.7±13.0% vs. 50.2±7.8%; p=ns). Out of 9 patients with normal LVEF and normal GLS, the segmental LS resulted better in non-compacted cardiac segments vs. compacted ones (-20.0±4.6% vs. -17.5±4.9%; p=0.03). This was mainly due to an increase deformation of endocardial layers of non-compacted segments (-26.4±6.6% vs. -19.7±6.6%; p≤0.001), while epicardial layers were similar in compacted versus non-compacted segments. Conclusions LVNC represents a poorly understood condition where a mixture of genetic and molecular mechanisms create a fertile substrate for the origin of ventricular arrhythmias. Our population reflects this pattern by showing a high percentage (5.5%/year) of patients experiencing the composite outcome. GLS was higher in non-compacted segments due to an apparent hyperdeformation of endocardial layers. In our opinion, this evidence represents a valid resource and a useful weapon to distinguish LVNC from other differential diagnoses such as, for example, dilated cardiomyopathy.

Abstract Introduction Cardiac amyloidosis (CA) is an underdiagnosed and heterogeneous cardiac disease characterized by the extracellular deposition of misfolded proteins in the cardiac tissue. Clinical manifestations are heterogeneous leading to progressive heart failure, often complicated by arrhythmias and conduction system disease. Among several sign and symptoms that are suspicious for the disease, named “red flags”, disproportionally low QRS voltages on the ECG has been described. Purpose The aim of this prospective observational study is to evaluate potential prognostic features of QRS amplitude in AL e ATTR CA patients. Methods All consecutive patients admitted to the Cardiomyopathy Clinic of our institution have been enrolled after receiving CA diagnosis, according to the current guidelines. We included all patients ≥18 years with a diagnosis of CA and written informed consent. A complete assessment including a standard 12-lead electrocardiogram (ECG) and echocardiogram was performed at enrollment. Low QRS voltages (LQRSV) was defined as a QRS total amplitude of ≤5 mm in every limb leads and ≤10 mm in every precordial lead. LQRSV was tested as an independent predictor of death from all causes (primary endpoint), hospitalization from cardiovascular causes, ventricular and supraventricular arrhythmias. Results Sixty patients (46 males, 77±12 years old) were enrolled, of which 18 (30%) met the criteria for LQRSV. Patients with LQRSV presented more frequently with an history of ventricular arrhythmia (27.8% vs. 6.7%, p=0.04), a lower left ventricular diastolic volume (31±7 vs. 44±18 ml/m2; p=0.04), and higher retinol-binding-protein 4 (9.3±2.2 vs 3.2±1.5 mg/dl; p=0.02). No differences were seen in the primary outcome (46% vs. 50%; p=NS; Figure 1) or in the secondary ones (cardiovascular hospitalization 25% vs. 21%; ventricular arrhythmias 12% vs 4%; supraventricular arrhythmias 29% vs 19%; all p=NS) between the two groups during a median follow up of 1.1 year. Conclusions In the present cohort of CA patients LQRSV did not emerge as independent predictor of all-cause mortality at 1 year. Although LQRSV is a recognized diagnostic “red-flag” in the work-up of CA, its role as prognostic marker remains unclear. Further studies with a longer follow-up are needed to better define the prognostic role of LQRSV among CA patients. Funding Acknowledgement Type of funding sources: None.

Abstract Introduction Left ventricular non compaction (LVNC) cardiomyopathy is an often underdiagnosed disease characterized by a thickened myocardium with a two-layered structure. Clinical presentations are very variable, ranging from an apparent lack of functional anomalies to heart failure, ventricular arrhythmias and, in some cases, even ischaemic stroke. Despite great improvements in diagnostic performance, there is still a wide lack of evidence regarding prognosis and management of affected patients. Purpose The aim of the present study was to investigate predictors of cardiovascular death or cardiovascular-related hospitalization in patients with LVNC over a long-term follow-up. Methods All consecutive patients with a definite diagnosis of LVNC admitted to the Cardiomyopathy Clinic of our institution from Jan 2015 to Dec 2020 were consecutively enrolled. Inclusion criteria were an age ≥18 years old and a diagnosis of LVNC made either by MRI or echocardiography. Exclusion criteria were a life expectancy ≤1 year and the inability to express informed consent for the study. All patients were follwed-up every six months. The primary endpoint was a composite of cardiovascular death and unplanned cardiovascular hospitalization. Results Twenty-one patients (14 male, age 40±17 years) meeting the inclusion criteria were prospectively enrolled and followed-up for a median of five years. LVNC patients with a previous history of supraventricular tachycardia at the time of diagnosis are more likely to meet the primary composite endpoint during follow-up (60% vs. 18%; p=0.048; Figure 1). On the other hand, neither LVEF (measured either with echo or CMR) nor functional status were associated with a significantly increased risk of the composite endpoint (all p=NS). Other significant predictors of increased risk include history of OSAS (z2 = 4.158), active/previous smoking (z2 = 6.279), and ST-segment alterations (z2 = 4.158). NC/C, as measured by either echo or CMR, was not a predictor of cardiovascular events (HR 0.18; 95% CI 0.31–1.08; p=NS). Conclusions Our data show how, in patients with LVNC, supraventricular tachycardias are related to worse outcomes and their presence should prompt a closer follow-up in order to detect possible adverse events. ST-segment alterations, OSAS and smoking are also related to a poorer prognosis, but their relevance should be further assessed. Surprisingly, in our sample LVEF and NC/C ratio were not predictors of worse outcomes; the reason might be that in LVNC patients mortality and cardiovascular hospitalizations resemble complex genetic and molecular mechanisms that differentiate them from other cardiomyopathies, but the paucity of the population prevents us from making wider inferences. Funding Acknowledgement Type of funding sources: None.