Cardiac amyloidosis (CA) is a restrictive cardiomyopathy characterized by deposition of amyloid in the myocardium and recent studies revealed it is more frequently seen than we thought. Advances in diagnosis and treatment have been made over the last few years that make it desirable to diagnose CA without delay, and that may require extra education. An online survey was conducted among cardiologists from Romania, representing the first assessment of the knowledge of CA among them, with 195 cardiologists answering the questionnaire. There was a wide variation in their knowledge regarding CA. Our participants had limited experience with CA and reported a significant delay between first cardiac symptoms and diagnosis. We address the gaps in knowledge that were identified as educational opportunities in the main identified areas: prevalence and treatment of wild type transthyretin amyloidosis (ATTRwt), prevalence of variant transthyretin amyloidosis (ATTRv) in Romania, diagnosis of CA, the delay in CA diagnosis and available treatment options. Awareness among cardiologists is the most important challenge in diagnosing CA. Romanian cardiologists are partially aware of this topic, but there are still gaps in their knowledge. Educational programs can improve screening of patients with a high suspicion for this progressive condition the prognosis of which has been dramatically changed by the new treatment options.

Cardiac amyloidosis (CA) is a restrictive cardiomyopathy characterized by deposition of amyloid in the myocardium and recent studies revealed it is more frequently seen than we thought. Advances have been made over the last years, but a delayed diagnosis is frequently seen. An online survey was conducted among cardiologists from Romania representing the first assessment of the knowledge of CA among them with 195 cardiologists answering the questionnaire. There was a wide variation in their knowledge regarding CA. Our participants had few experience with CA and reported a significant delay between first cardiac symptom and diagnosis. Around one half of them did not seem familiar with the noninvasive diagnostic algorithm and with the wild-type transthyretin amyloidosis (ATTRwt). Even the participants who are aware of this condition and the available treatment options stated this is a rare disease and there is no disease modifying treatment available for ATTRwt. Awareness among cardiologists is the most important challenge in diagnosing CA. Romanian cardiologists are partially aware of this topic, but there are still gaps in their knowledge. Educational programs can improve screening of patients with a high suspicion for this progressive condition whose evolution has been dramatically changed by the new treatment options.

Background Systemic amyloidoses represent a heterogeneous group of diseases resulting from the deposition of misfolded proteins as amyloid fibrils into the extracellular matrix of different organs. Based on this precursor protein, cardiac amyloidosis (CA) can be most frequently classified as: light chain (AL) and transthyretin (ATTR) amyloidosis, with different management and prognosis. Purpose The purpose of this study is to establish a differential diagnosis algorithm targeted towards these two most frequent subtypes of CA. Although confirmation through invasive or non-invasive diagnostic algorithms is still mandatory for a final diagnosis, a series of clinical, paraclinical and imaging differences could possibly guide the choice for more complex diagnostic steps. Methods We prospectively included all consecutive patients with ATTR and AL evaluated between 2018 and 2022 in our center. All patients had a complete clinical, paraclinical and imaging evaluation including myocardial deformation study, and confirmation of the final diagnosis, according to the current international recommendations. Results The study population included 81 patients divided into 2 groups: ATTR (group 1, n=32: 30 variant and 2 wild type) and AL (group 2, n=49). ATTR patients were younger (50.7±13.9 vs. 60.2±7.3 years, p=0.0001), had predominantly more neurological symptoms, milder cardiac symptoms and lower values of cardiac biomarkers than AL: NT-proBNP (3095±4433 vs. 10382±9008 ng/ml, p=0.001) and high sensitive troponin I (0.0129±0.01 vs 0.177±0.2 ng/ml, p=0.0002), with better renal function (mean GFR 84.74±26.9 vs. 64.5±29.45 mL/min, p=0.003). We found no significant differences in terms of ECG changes. Moreover, at similar left ventricular (LV) wall thickness and ejection fraction, ATTR group had less pericardial effusions (53.6 vs. 86.8%, p=0.0027), better LV global longitudinal strain (−12.0±3.7 vs. −9.7±4.6%, p=0.03), RV strain (RVFW strain −19.7±6.2 vs. −14.5±11.0%, p=0.03) and also better reservoir and contractile function of the LA (LASr 17.2±12.3 vs. 11.2±7.4%, p=0.02). Based on this multiparametric comparison we proposed a prediction algorithm to differentiate between the 2 forms of CA. A score of equal or more than 4 from a maximum of 9 points, has been able to differentiate between AL and ATTR with a sensitivity and specificity of 78 and 80%, respectively; AUC= 0.82. Conclusions CA is a complex entity and requires extensive testing through serum biomarkers, imaging, and invasive confirmation of amyloid infiltration in some cases. This study highlighted a series of non-invasive checkpoints, which can be useful in guiding the decision making process towards a more accurate and rapid differential diagnosis, in cases where a final diagnosis is crucial to be immediately established. Funding Acknowledgement Type of funding sources: None.

Introduction Fabry disease (FD) is an X-linked rare lysosomal storage disease caused by mutations in the GLA gene which lead to decrease in α Gal A enzyme activity and tissue accumulation of lysosomal globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3). Due to X linked transmission, males are hemizygous, and females are heterozygous and were initially thought to be unaffected. However, women with FD can vary from asymptomatic, mildly symptomatic, to severely symptomatic as males. The aim of this study is to evaluate the particularities of FD presentation, cardiac imaging and management in females from the full Romanian FD cohort as compared to male patients. Methods This study included all consecutive patients diagnosed in or referred to our center with FD between 2014–2021. All patients had a complete clinical, biological and cardiac imaging workup. Results During the inclusion interval, data from 66 consecutive Romanian FD patients (37 women and 29 men) from 29 unrelated families were collected. Diagnosing mode in FD women differs compared to men (p<0.001): most women were diagnosed through family screening or by a cardiologist, while most men were diagnosed by nephrologists. Women had higher levels of α Gal A levels (1.3±0.8 μmol/L/h vs 0.5±0.7 μmol/L/h, normal cutoff >1.2) (p<0.001) and smaller levels of lyso-GB3 (5.8±2.6 ng/ml vs 110±35.6 ng/ml, normal cutoff<3.8) (p<0.001). More women are asymptomatic carriers than men (27% vs 3.4%), but when symptoms were present, they could be as severe as in men. Enrolled women were older (50.9±16.3 vs 41±14.9 years, p=0.014), diagnosed later (46.8±16.8 vs 32.7±14.3 years, p<0.001) and had later symptom onset of the disease compared with men (38.1±14.4 vs 20.3±14.9 years, p<0.001). Women had less angiokeratomas (p=0.001) and hypohydrosis (p=0.04), with no difference in cornea verticillata or ENT involvement. Both women and men developed cardiac symptoms starting from the fifth decade, with no differences in terms of angina, NYHA class, syncope between sexes. Women tend to have a lower prevalence of LVH compared to men (p=0.052), with no differences regarding ejection fraction or global longitudinal strain between genders. Regarding other organs involved, women were equally affected as men from acroparesthesia and stroke, with similar age at first cerebrovascular event. Women had milder kidney involvement (stages 1 and 2) when compared to men (56.8% vs 37.9%, p=0.004). Regardless of these findings, it appeared that women were less treated with pathogenic therapy comparing to men (48.6% vs 82.7%) (p=0.004). Conclusions Women with FD are not merely genetic carriers as they can be as affected as men. However, they benefit later from diagnosis and less of pathogenic therapy. Further studies with more female participations are needed to better understand the Fabry burden and needs in women. Funding Acknowledgement Type of funding sources: None.

Funding Acknowledgements Type of funding sources: None. Background Cardiac amyloidosis (CA) is characterized by the extracellular deposition of amyloid fibrils in the heart, mostly light chain (AL) and transthyretin (ATTR) amyloidosis. Recent data have improved both the recognition and treatment of ATTR CA. The therapeutic advances in ATTR CA led to improvement in survival and quality of life, but less detailed evidence is available for the myocardial changes during treatment. Purpose The aim of this pilot study is to evaluate cardiac response under treatment with the genetic "silencer" patisiran in patients with mixed phenotype ATTR with an indication for neuropathy, using multimodal imaging techniques. Methods We prospectively evaluated consecutive patients with mixed phenotype v-ATTR amyloidosis who had received patisiran for aggravated polyneuropathy since 2021. All patients had a complete clinical, paraclinical and comprehensive echocardiography evaluation including myocardial deformation assessment, prior to receiving patisiran and at most recent follow-up. Five of our patient had complementary cardiac magnetic resonance (CMR) at baseline and 1 year follow-up. Results We included 13 patients (mean age 48.1±5.4 yo, 4 men) monitored for the therapeutic response based on the current ESC expert consensus on the monitoring of ATTR CA. They have all been diagnosed with variant ATTR with the same mutation - Glu54Gln - with severe mixed phenotype: both cardiac involvement and autonomous and peripheral polyneuropathy. Time since first diagnosis was 3.4 ±0.8 years, and they had all received Tafamidis 20 mg before being switched to patisiran. At 1 year of treatment, there was no significant change in NYHA functional class, but 6 MWT could not be performed due to impairment related to polyneuropathy. There was no significant change in NT-proBNP during treatment (median at baseline 543 pg/ml vs follow-up 255 pg/ml, p = 0.75). Echocardiography showed no significant change in LV maximal wall thickness (MWT), LV mass index (LVMi), LVEF, stroke volume and myocardial deformation (LV GLS) (Table). Based on these echocardiographic and biological parameters we considered our patients stationary. Meanwhile, CMR confirmed no significant difference between baseline and follow-up in LVMi, MWT and LVEF. Moreover, there was no difference in the visually assessed LGE distribution, native T1, T2 and ECV values (Table, Case vignette). Based on the tissue characterization all patients were considered stable regarding ATTR-CA evolution. We found strong correlations between echo and MRI for LVEF (r=0.71), LVEDV (r=0.67) and MWT (r=0.66). Conclusions Even if used after more than 3 years from first diagnosis in our cohort, structural and functional cardiac parameters remain stable under patisiran therapy. Our study highlights the utility of introducing CMR as an alternative to echocardiography in ATTR-CA disease monitoring protocols, based on its high accuracy, strong correlations and complexity of derived parameters.