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BackgroundA small but significant reduction in left ventricular (LV) mass after 18 months of migalastat treatment has been reported in Fabry disease (FD). This study aimed to assess the effect of migalastat on FD cardiac involvement, combining LV morphology and tissue characterisation by cardiac magnetic resonance (CMR) with cardiopulmonary exercise testing (CPET).MethodsSixteen treatment-naïve patients with FD (4 women, 46.4±16.2 years) with cardiac involvement (reduced T1 values on CMR and/or LV hypertrophy) underwent ECG, echocardiogram, troponin T and NT-proBNP (N-Terminal prohormone of Brain Natriuretic Peptide) assay, CMR with T1 mapping, and CPET before and after 18 months of migalastat.ResultsNo change in LV mass was detected at 18 months compared to baseline (95.2 g/m2(66.0–184.0) vs 99.0 g/m2(69.0–121.0), p=0.55). Overall, there was an increase in septal T1 of borderline significance (870.0 ms (848–882) vs 860.0 ms (833.0–875.0), p=0.056). Functional capacity showed an increase in oxygen consumption (VO2) at anaerobic threshold (15.50 mL/kg/min (13.70–21.50) vs 14.50 mL/kg/min (11.70–18.95), p=0.02), and a trend towards an increase in percent predicted peak VO2(72.0 (63.0–80.0) vs 69.0 (53.0–77.0), p=0.056) was observed. The subset of patients who showed an increase in T1 value and a reduction in LV mass (n=7, 1 female, age 40.5 (28.6–76.0)) was younger and at an earlier disease stage compared to the others, and also exhibited greater improvement in exercise tolerance.ConclusionIn treatment-naïve FD patients with cardiac involvement, 18-month treatment with migalastat stabilised LV mass and was associated with a trend towards an improvement in exercise tolerance. A tendency to T1 increase was detected by CMR. The subset of patients who had significant benefits from the treatment showed an earlier cardiac disease compared to the others.Trial registration numberNCT03838237.

Background Cardiovascular death is the leading cause of mortality in patients affected by Fabry Disease (FD). Cardiac magnetic resonance (CMR) is the gold-standard imaging modality to assess FD heart involvement and enzyme replacement therapy (ERT) has the potential to slow or revert FD organ involvement and dysfunction. However, the effect of ERT on cardiac disease progression remains undefined. Thus, we performed a systematic review and meta-analysis to assess the impact of ERT on CMR parameters in FD patients. Methods Data search was conducted from inception through June 1, 2022, using the following Medical Subject Heading terms: “Fabry Disease” AND (“Cardiac MRI” OR “Cardiac Magnetic Resonance” OR “Cardiovascular Magnetic Resonance” OR “CMR”) AND (“ERT” OR “Enzyme Replacement Therapy”. Studies were included if contemplated FD patients undergoing baseline and follow-up CMR after ERT. Pre-defined study outcomes were the change of i) left ventricular wall mass (LVM; grams); ii) LVM indexed (grams/mq); iii) maximum left ventricular wall thickness (MLVWT, mm), iv) Late gadolinium enhancement (LGE; % of LVM) and v) native-T1 mapping (msec) between baseline and follow-up CMR. The study protocol was registered in the PROSPERO database (CRD42022336223). Results Ten studies including 517 FD patients were included. Between baseline and follow-up CMR, there was a significant decrease in LVM (pooled hazard ratio: -19.5 grams [95% CIs, -34.3; -4.63]), LVM indexed (-2.84 grams/mq [95% CIs, -5.24; -0.44]), MLVWT (-0.96 mm [95% CIs -1.9; -0.02]), and an increase in LGE (0.8% [95% CIs, 0.47; 1.14). T1-mapping did not significantly change (pooled hazard ratio: 6.12 msec [95% CIs -2.39; 14.62]). There was publication bias in LVM (Egger test: p-value = 0.047) but not in LVM index, MLVWT, T1-mapping and LGE. Conclusion In a pooled-analysis including 427 FD patients treated with ERT undergoing baseline and follow-up CMR, there was a significant decrease in LVM, LVM indexed, and LVMWT. In contrast, there was an increase in LGE extent whereas native-T1 mapping values did not significantly change.

Objectives To elaborate an ECG-based nomogram estimating the probability to detect cardiac involvement by cardiac magnetic resonance (CMR) in Fabry Disease (FD). Methods 119 FD patients and 26 healthy controls underwent ECG and CMR. Test (n = 88, 60%) and validation cohorts (n = 57, 40%) were randomly derived. Cardiac involvement was defined as the presence of low myocardial T1 value, a CMR-surrogate of myocardial glycosphingolipid storage. ECG changes associated with low T1 value were identified in the test cohort, included in the nomogram and then tested in the validation cohort. Results Sokolow-Lyon index (AUC = 0.769), ratio between P-wave and PR-segment durations (Pwave/PRsegment) (AUC = 0.778), QRS duration (AUC = 0.703), QT (AUC = 0.769) duration were independently associated with the presence of low T1 on CMR at multivariate analysis. An ECG-based nomogram including these four parameters was accurate in identifying patients with CMR evidence of glycosphingolipid storage (c-index of the derived-nomogram = 0.90 in the test group; 0.81 in the validation group). Conclusion We propose a practical ECG-based nomogram accurately estimating the probability to detect low T1 values by CMR in FD patients. The application of this tool in clinical practice could improve early detection of FD cardiac involvement.

2D speckle tracking echocardiography (2DSTE) is superior to standard echocardiography in the assessment of subtle right ventricle (RV) systolic dysfunction. In this study we aimed to: 1) test the hypothesis that 2DSTE may unveil subtle RV systolic dysfunction in patients with Fabry disease; 2) investigate whether the physiologic difference between the 3-segment (RV-FWS) and the 6-segment (RV-GLS) RV strain (∆RV strain) is preserved in Fabry patients.Standard echocardiography and 2DSTE were performed in 49 Fabry patients and 49 age- and sex-matched healthy controls. Fabry patients were divided in two groups according to the presence/absence of left ventricular hypertrophy (LVH+: left ventricular wall thickness 12 mm, 49% of total Fabry patients). RV systolic function assessed by standard echocardiography was normal in the majority of Fabry patients (92%) while RV-GLS and RV-FWS were impaired in about 40%. RV-GLS and RV-FWS were significantly worse in patients LVH+ vs LVH- and vs controls (RV-GLS: LVH+ vs LVH-: -18.4 ± -4.3% vs -23.8 ± -3.1% p0.001; LVH+ vs controls: -18.4 ± -4.3% vs -23.9 ± -2.8% p0.001; RV-FWS: LVH+ vs LVH-: -21.8 ± -5.3% vs -26.7 ± -3.8% p = 0.002, LVH+ vs controls -21.8 ± -5.3% vs -26.8 ± -3.9% p0.001). No difference was found between LVH- patients and controls in both RV-GLS (p = 0.65) and RV-FWS (p = 0.79). ∆RV strain was similar among the groups.In Fabry cardiomyopathy impaired RV-GLS and RV-FWS is a common finding, while RV strain is preserved in Fabry patients without overt cardiac involvement. The physiologic difference between RV-FWS and RV-GLS is maintained in Fabry patients, regardless of the presence of cardiomyopathy.

Fabry disease (FD) is a rare X-linked inherited lysosomal storage disorder caused by deficient α-galactosidase A activity that leads to an accumulation of globotriasylceramide (Gb3) in affected tissues, including the heart. Cardiovascular involvement usually manifests as left ventricular hypertrophy, myocardial fibrosis, heart failure, and arrhythmias, which limit quality of life and represent the most common causes of death. Following the introduction of enzyme replacement therapy, early diagnosis and treatment have become essential to slow disease progression and prevent major cardiac complications. Recent advances in the understanding of FD pathophysiology suggest that in addition to Gb3 accumulation, other mechanisms contribute to the development of Fabry cardiomyopathy. Progress in imaging techniques have improved diagnosis and staging of FD-related cardiac disease, suggesting a central role for myocardial inflammation and setting the stage for further research. In addition, with the recent approval of oral chaperone therapy and new treatment developments, the FD-specific treatment landscape is rapidly evolving.

Aims In Fabry cardiomyopathy, left ventricular outflow tract obstruction mimicking hypertrophic cardiomyopathy is a very rare finding, with few cases reported and successfully treated with cardiac surgery. In our population of patients with Fabry disease and severe left ventricular hypertrophy (LVH) at the time of diagnosis, we observed an evolution towards a midventricular obstructive phenotype. Methods and results We present a case series of three classically affected Fabry male patients with significant diagnostic delay and severe cardiac involvement (maximal wall thickness >20 mm) at first evaluation. All patients developed midventricular obstructive form over time despite prompt initiation and optimal compliance to enzyme replacement therapy. The extension and distribution of the LVH, involving the papillary muscles, was the main mechanism of obstruction, unlike the asymmetric septal basal hypertrophy and the mitral valve abnormalities commonly seen as substrate of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy. Conclusions Fabry cardiomyopathy can evolve over time towards a midventricular obstructive form due to massive LVH in classically affected men with significant diagnostic delay and severe LVH before enzyme replacement therapy initiation. This newly described cardiac phenotype could represent an adverse outcome of the disease.

Aims Right ventricular hypertrophy (RVH) is a common finding in Anderson–Fabry disease (AFD), but the prognostic role of right ventricular (RV) involvement has never been assessed. The aim of our study was to evaluate the prognostic significance of RVH and RV systolic function in AFD. Methods and results Forty‐five AFD patients (56% male patients) with extensive baseline evaluation, including assessment of RVH and RV systolic function, were followed‐up for an average of 51.2 ± 11.4 months. RV systolic function was assessed by standard and tissue Doppler echocardiography. Cardiovascular events were defined as new‐onset atrial fibrillation (AF), sustained ventricular arrhythmias, heart failure, or pacemaker/implantable cardioverter defibrillator implantation; renal events were defined as progression to dialysis and/or renal transplantation or significant worsening of glomerular filtration rate; and cerebrovascular events were defined as transient ischaemic attack or stroke. Fourteen patients (31.1%) presented RVH, while RV systolic function was normal in all cases. During the follow‐up period, 13 patients (28.8%, 11 male) experienced 18 major events, including two deaths. Cardiovascular events occurred in eight patients (17.7%). The most common event was pacemaker/implantable cardioverter defibrillator implantation (six patients, 13.3%), followed by AF (three cases, 6.6%). Only one case of worsening New York Heart Association class (from II to III and IV) was observed. Ischaemic stroke occurred in three cases (6.6%). Renal events were recorded in three patients (6.6%). At univariate analysis, several variables were associated with the occurrence of events, including RVH (HR: 7.09, 95% CI: 2.17 to 23.14, P = 0.001) and indexes of RV systolic function (tricuspid annular plane systolic excursion HR: 0.77, 95% CI: 0.62 to 0.96, P = 0.02; and RV tissue Doppler systolic velocity HR: 0.76, 95% CI: 0.61 to 0.93, P = 0.01). At multivariate analysis, proteinuria (HR:8.3, 95% CI: 2.88 to 23.87, P

Background Time-resolved three-directional velocity-encoded (4D flow) magnetic resonance imaging (MRI) enables the quantification of left ventricular (LV) intracavitary fluid dynamics and energetics, providing mechanistic insight into LV dysfunctions. Before becoming a support to diagnosis and patient stratification, this analysis should prove capable of discriminating between clearly different LV derangements. Purpose To investigate the potential of 4D flow in identifying fluid dynamic and energetics derangements in ischemic and restrictive LV cardiomyopathies. Study Type Prospective observational study. Population Ten patients with post-ischemic cardiomyopathy (ICM), 10 patients with cardiac light-chain cardiac amyloidosis (AL-CA), and 10 healthy controls were included. Field Strength/Sequence 1.5 T/balanced steady-state free precession cine and 4D flow sequences. Assessment Flow was divided into four components: direct flow (DF), retained inflow, delayed ejection flow, and residual volume (RV). Demographics, LV morphology, flow components, global and regional energetics (volume-normalized kinetic energy [KEV] and viscous energy loss [ELV]), and pressure-derived hemodynamic force (HDF) were compared between the three groups. Statistical Tests Intergroup differences in flow components were tested by one-way analysis of variance (ANOVA); differences in energetic variables and peak HDF were tested by two-way ANOVA. AP-value of Results ICM patients exhibited the following statistically significant alterations vs. controls: reduced KEV, mostly in the basal region, in systole (−44%) and in diastole (−37%); altered flow components, with reduced DF (−33%) and increased RV (+26%); and reduced basal–apical HDF component on average by 63% at peak systole. AL-CA patients exhibited the following alterations vs. controls: significantly reduced KEVat the E-wave peak in the basal segment (−34%); albeit nonstatistically significant, increased peaks and altered time-course of the HDF basal–apical component in diastole and slightly reduced HDF components in systole. Data Conclusion The analysis of multiple 4D flow-derived parameters highlighted fluid dynamic alterations associated with systolic and diastolic dysfunctions in ICM and AL-CA patients, respectively.

ObjectivesTo evaluate the role of the ECG in the differential diagnosis between Anderson-Fabry disease (AFD) and hypertrophic cardiomyopathy (HCM).MethodsIn this multicentre retrospective study, 111 AFD patients with left ventricular hypertrophy were compared with 111 patients with HCM, matched for sex, age and maximal wall thickness by propensity score. Independent ECG predictors of AFD were identified by multivariate analysis, and a multiparametric ECG score-based algorithm for differential diagnosis was developed.ResultsShort PR interval, prolonged QRS duration, right bundle branch block (RBBB), R in augmented vector left (aVL) ≥1.1 mV and inferior ST depression independently predicted AFD diagnosis. A point-by-point ECG score was then derived with the following diagnostic performances: c-statistic 0.80 (95% CI 0.74 to 0.86) for discrimination, the Hosmel-Lemeshow χ2 6.14 (p=0.189) for calibration, sensitivity 69%, specificity 84%, positive predictive value 82% and negative predictive value 72%. After bootstrap resampling, the mean optimism was 0.025, and the internal validated c-statistic for the score was 0.78.ConclusionsStandard ECG can help to differentiate AFD from HCM while investigating unexplained left ventricular hypertrophy. Short PR interval, prolonged QRS duration, RBBB, R in aVL ≥1.1 mV and inferior ST depression independently predicted AFD. Their systematic evaluation and the integration in a multiparametric ECG score can support AFD diagnosis.

Background: Brugada syndrome (BrS) is considered a purely electrical disease with variable electrical substrates. Variable rates of mechanical abnormalities have been also reported. Whether exists a link between electrical and mechanical abnormalities has never been previously explored. This investigational physiopathological study aimed to determine the relationship between the substrate size/location, as exposed by ajmaline provocation, and the severity of mechanical abnormalities, as assessed by cardiac magnetic resonance in patients with BrS. Methods: Twenty-four consecutive high-risk patients with BrS (mean age, 38±11 years, 17 males), presenting with malignant syncope and documented polymorphic ventricular tachycardia/ventricular fibrillation, and candidate to implantable cardioverter defibrillator implantation, underwent cardiac magnetic resonance and electroanatomic maps. During each examination, ajmaline test (1 mg/kg over 5 minutes) was performed. Cardiac magnetic resonance findings were compared with 24 age, sex, and body surface area-matched controls. In patients with BrS, the correlation between the electrical substrate extent and right ventricular regional mechanical abnormalities before/after ajmaline challenge was analyzed. Results: After ajmaline, patients with BrS showed a reduction of right ventricular (RV) ejection fraction ( P P P P P 2 to 14.2±7.3 cm 2 ( P r =−0.830, P Conclusions: BrS is a dynamic RV electromechanical disease, where functional abnormalities correlate with the maximal extent of the substrate size. These findings open new lights on the physiopathology of the disease. Registration: URL: https://clinicaltrial.gov ; Unique identifier: NCT03524079.

Background Cardiac magnetic resonance (CMR) plays a central role in the diagnosis, follow-up and prognostic stratification of acute myocarditis. Several CMR features, including the extent of late gadolinium enhancement (LGE) at baseline, have been proposed as factors associated with a worse outcome. Recent studies evaluated temporal evolution of LGE and edema repeating CMR either at 6 months or at 12 months, demonstrating that persistence or worsening of LGE represents a negative prognostic marker. However, the time-course of edema resolution and LGE stabilization is currently unknown and therefore the optimal timing to repeat CMR for acute myocarditis prognostic stratification remains unclear. Purpose We aimed to assess the time course of edema and LGE evolution in order to identify the optimal timing to repeat CMR in patients with acute myocarditis. Methods We enrolled 36 patients with a diagnosis of acute myocarditis according to ESC position statement definition. All patients underwent CMR at clinical presentation (CMR-1), after 3–4 months (CMR-2) and after 12-months (CMR-3) follow-up. CMR evaluation included assessment of edema and LGE, and evaluation of structural and functional parameters including left (LVEF) and right ventricular ejection fraction (RVEF), left (LVGLS) and right ventricular global longitudinal strain (RVGLS) and indexed left ventricular mass (iLVM). After CMR-3 all patients were followed-up by yearly clinical evaluation, electrocardiogram (ECG) and 2D-echocardiography. Results The mean age was 28,8±10,3 years with 35 (97%) being male. All patients showed edema and LGE at CMR-1 with a LVEF of 58,5±12,2. At CMR-2 a significant reduction of edema (T2 positive segments 0,4±0,9 vs. 4,1±3,2 p Conclusions In most patients with acute myocarditis a complete resolution of the inflammatory process with LGE stabilization and normalization of left ventricular function and mass can be observed after 3–4 months. Further CMR assessment should limited to patients with persisting oedema at 3–4 months CMR. Our findings suggest to redefine the follow-up schedule and imaging-based prognostic stratification strategies in patients with acute myocarditis. Funding Acknowledgement Type of funding sources: None. Figure 1

Background Fabry disease (FD) is a rare x-linked lysosomal storage disease characterized by accumulation of glicosphingolipids in several organs, including the heart. Cardiac involvement manifests as left ventricular (LV) hypertrophy, often complicated by myocardial fibrosis. The impact of disease on functional capacity is not well defined, as well as the potential gender-related differences. Aim To evaluate the functional capacity in a cohort of FD patients with different degree of cardiac involvement. Methods Seventy-two patients were prospectively enrolled from March 2015 to December 2019. Patients underwent cardiac magnetic resonance (CMR) and cardiopulmonary exercise test (CPET) with cycle ergometer. In addition to standard CPET parameters, Chronotropic Index (CI) was calculated as (HR max − HR rest) / (HR max predicted − HR rest), adjusting with HR max predicted calculated as 119 + (HR rest/2) − (age/2) in case of beta-blockers treatment. Results CMR showed left ventricle (LV) hypertrophy (LV mass greater than normal reference value) in 36.1% of patients, LGE and reduced T1 values were detected in 30.6% and 59.7% of subjects respectively. Twenty-eight patients were males (39%), the median age was 40 (28–54) [median (25th–75th)] years and only 11 (15%) subjects were on beta-blockers. All subjects performed a maximal test [RQ max = 1.21 (1.14–1.26)] using a ramp protocol of 15 (15–20) Watt. The absolute peakVO2 was 18.2 (15.75–24.08) mL/min/kg, whilst the percentage of predicted peakVO2 was 67.7 (57.3–76.6)%. The chronotropic response of the overall population was characterized by reduced peak heart rate (HRmax) [80.3 (73.8–87.6)% of predicted], and diminished chronotropic index (CI) [0.67 (0.55–0.77) normal value: 0.80], but preserved heart rate reserve (HRR) [21 (12–28) bpm]. Ventilatory efficiency was preserved [VE/VCO2 = 25.70 (23.18–28.00)]. At gender analysis, men showed higher absolute peakVO2 [men vs females: 19.95 (17.20–28.28) vs 17.80 (15.50–21.28) mL/min/kg, p=0.02] but lower percentage of predicted [64.24 (52.58–70.61) vs 70.75 (59.05–78.02)%, p Conclusions This large cohort of FD patients with different degree of cardiac involvement showed a significantly impaired functional capacity, mainly characterized by relevant chronotropic incompetence (independent from the use of beta-blockers), consistent with systemic autonomic dysfunction. The degree of chronotropic incompetence was similar between the genders, but females showed higher predicted peakVO2 despite a lower peak O2 pulse. Funding Acknowledgement Type of funding sources: None.

Background Fabry Disease (FD) is a rare X-linked lysosomal storage disorder. Since 2016, pharmacological chaperone Migalastat has been approved for treatment of FD patients with amenable mutations to stabilize defective forms of the enzyme α-galactosidase A. A small but significant reduction in left ventricular (LV) mass after 18 months of Migalastat treatment has been previously reported by echocardiography. However, an integrated assessment of the effect of Migalastat on cardiac involvement, combining LV morphology and tissue composition by CMR with exercise capacity by cardiopulmonary test, is lacking. Purpose To determine the effects of 18 month treatment with Migalastat on LV mass, native T1 value and functional capacity in naïve patients with genetically confirmed FD cardiomyopathy. Methods Sixteen treatment naïve FD patients (4 females, mean age 46.4±16.2) with amenable mutations and signs of cardiac involvement underwent CMR with T1 mapping and cardio-pulmonary testing before and after 18 months of migalastat therapy as a part of MAIORA Study. Cardiac involvement was defined as presence of reduced native T1 values at CMR (a surrogate of myocardial glycosphingolipid storage) and/or LV hypertrophy (LVH). Nine patients (56%, 2 females, mean age 56.4±12.7 years) had LVH at baseline. Results Migalastat treatment was well tolerated in all patients, with no serious adverse event. No change in LV mass was detected at 18 months compared to baseline (95.2 (66.0–184.0) vs 103.0 (71.0–182.0) g/m2; p=0.5516). The same result was found after stratifying patients according to presence/absence of Late Gadolinium Enhancement (LGE) (LGE+ n=8, 2 females, mean age 56.2±13.1 years). There was a trend towards an increased native septal T1 value (870.0 (848–882) vs 860.0 (833.0–875.0) ms at baseline; p 0.056) with unchanged extracellular volume (ECV) (0.26 (0.23–0.028) vs 0.26 (0.22–0.29) at baseline; p 0.276) in the overall cohort. An improvement in functional capacity with a trend towards an increase in percent-predicted peak VO2 (72.0 (61.25–80.75) vs 67.0 (45.2–79.2) at baseline; p 0.056) and a significant increase in VO2 at anaerobic threshold (14.8 (12.6–20.0) vs 13.10 (6.8–18.6) ml/kg/min at baseline; p 0.004) was reported in the total population. Conclusion In treatment naïve FD patients with amenable mutations and signs of early or overt cardiac involvement, 18-month treatment with Migalastat stabilized LV mass both in patients with and without LGE and was associated with an improvement in exercise tolerance. The trend towards an increase in T1 value associated with unchanged ECV suggests partial clearance of cardiomyocyte glycoshingolipid storage. These real-world data are consistent with a beneficial impact of migalastat on the progression of cardiac involvement in FD. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amicus Therapeutics

Funding Acknowledgements Type of funding sources: None. Background Left ventricular (LV) diastolic dysfunction (DD) is a hallmark of hypertrophic cardiomyopathy (HCM) and its phenocopies, such as Fabry disease (FD). Together with left atrial (LA) size, LA function is emerging as a sensitive marker of the adaptive changes to backward transmission of LV cardiac filling pressure, thus implementing DD assessment. Additionally, both HCM and FD are characterized by a primitive atrial myopathy, but LA morpho-functional changes in HCM and FD have never been directly compared. More recently, LA strain by Cardiovascular Magnetic Resonance Feature Tracking (CMR-FT) has been demonstrated to be a feasible and reproducible tool to explore LA function. Purpose To compare LA morpho-functional changes in HCM and FD and to explore their correlation with tissue alterations. Methods 15 HCM and 15 sex-, age- and LV mass index-matched FD patients underwent CMR (Magnetom Aera 1.5T, Siemens) and Doppler Echocardiography for LV diastolic function assessment (E/e’ and DD grading from 0 to 3). LA phasic function was evaluated by CMR-FT strain (Qstrain Medis). The software output included passive (εe, conduit function), active (εa, booster pump function) and total strain (εs, reservoir function), along with LA volumes and ejection fraction (EF). Late gadolinium enhancement (LGE) was quantified as a percentage of LV mass using the standard deviations (SDs) method (≥ 5 SDs). Interstitial fibrosis was assessed by extracellular volume (ECV) quantification in remote myocardium. All patients were in sinus rhythm. Results In the HCM group, the proportion of patients with DD grade 2-3 was only slightly higher than in FD (p 0.26). Accordingly, no significant difference was found in E/e’ value (p 0.78). Compared to FD, HCM patients showed more severe LA morpho-functional changes, including larger LA end-systolic volume (ESV) (113 ± 35 vs 84 ± 23 ml), lower LA EF (37 ± 7 vs 44 ± 9 %) and a greater reduction of εs (-20 ± 5 vs -25 ± 6 %) and εa (-10 ± 4 vs -15 ± 4 %) (all p < 0.05). LV size and function and the burden of fibrosis (LGE quantification and ECV) were comparable between the two groups. Interestingly, in HCM population, unlike in FD, LA morpho-functional measurements significantly correlated with tissue characterization parameters (LA ESV with LGE, r 0.56, p 0.03; εs and εa with ECV, r -0.51, p 0.05 and r -0.59, p 0.02, respectively). Conclusions LA morpho-functional alterations are much more severe in HCM compared to FD with similar degree of LV hypertrophy. A more severe atrial myopathy or different mechanisms of atrial damage in the two cardiomyopathies may explain these findings. LA CMR-FT analysis may represent a sensitive tool to discriminate between HCM and FD, although larger studies are needed to confirm this finding and the possible correlation with the occurrence of atrial arrhythmias and thromboembolic risk.

Funding Acknowledgements Type of funding sources: None. Background Increasing evidence suggests that left atrial (LA) deformation is a sensitive marker of diastolic dysfunction in hypertrophic phenotypes. However, there is little data about the impact of hypertension on LA function; furthermore, LA deformation in hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) has not been compared yet. Purpose The aim of this study is to compare atrial dimensions and function, evaluated by cardiovascular magnetic resonance feature tracking (CMR-FT) in patients with HHD, HCM and healthy subjects (HS). Methods 67 patients (20 HHD, 27 HCM, 20 HS) underwent CMR and were included in the study. Patients were matched for age, sex and BSA; HHD and HCM were also comparable for LV mass index and ejection fraction (EF). CMR-FT atrial strain analysis was performed using Qstrain, Medis software to obtain i) LA conduit function, ii) LA booster pump function), iii) LA reservoir function, iv) LA volumes and EF. Tissue Doppler echocardiography was used to assess diastolic function, including E/e’. LA stiffness was calculated as the ratio between E/e’ and LA reservoir. Both focal and interstitial myocardial fibrosis were assessed with LGE and extracellular volume (ECV) quantification. Results HHD and HCM showed impaired LA reservoir, conduit function and higher LA volumes vs HS (reservoir: 28 ± 11% and 28 ± 13% vs 41 ± 17%; conduit: 13 ± 7% and 13 ± 7% vs 22 ± 11%; LAESV: 76 ± 21 and 87 ± 22 vs 57 ± 19 ml respectively; all p ≤ 0.03). HHD and HCM were comparable for bi-ventricular morpho-functional parameters and ECV. HHD showed lower E/e’ values (8 ± 2 vs 16 ± 7, p = 0.002) and LA stiffness (0.23 ± 0.3 vs 0.74 ± 0.6, p 0.03), LA dimensions (LA area 13 ± 3 vs 16 ± 3 cm2/m2, p = 0.02 , LAESVi 41 ± 12 vs 48 ± 11 ml/m2, p = 0.05) and LGE extent (1 ± 2% vs 5 ± 5%, p = 0.001) as compared to HCM. Interestingly, HHD revealed a comparable reduced LA reservoir and conduit function (all p = 0.9) vs HCM. In HHD patients LA reservoir function was correlated with E/e’ (r -0.8, p = 0.02), but not in HCM. Conversely, LA reservoir function was correlated with LV mass index in HCM (r -0.5, p Conclusions HHD patients showed a similar and significant impairment of LA function, with lower LA dimensions and E/e’ compared to HCM with similar LV mass index and preserved function. CMR-FT atrial strain analysis could represent a useful tool for HHD management, able to detect diastolic dysfunction (and/or atrial dysfunction) earlier than traditional markers. Further studies are needed to explore the relationship of LA deformation to heart failure symptoms and atrial fibrillation occurrence and potential changes related to response to therapy.

It is debated whether percutaneous revascularization (PCI) of total coronary chronic occlusion (CTO) is superior to optimal medical therapy (OMT) in improving symptoms, left ventricular (LV) function and major adverse cardiac/cerebrovascular events (MACCE). Furthermore, CTO-PCI is a challenging technique, with lower success rate than in other settings. A systematic analysis of baseline LV function, infarction extent and ischaemic burden to predict response to revascularization has never been performed.To establish a CMR protocol to identify patients (pts) who can benefit most from CTO-PCI. Myocardial viability/ischaemia retains high biological plausibility as predictors of response to revascularization. Therefore, baseline viability (necrotic tissue extent, response to inotropic stimulation) and ischaemia (perfusion defect, wall motion abnormality during stress) will be studied as potential predictors of mechanical LV segmental improvement and ischaemic burden reduction in CTO territory (primary endpoint), LV remodelling and global function, Seattle Angina Questionnaire, and MACCE improvement (secondary endpoints) in the follow-up.Pts with CTO suitable for PCI undergo stress-CMR for viability/ischaemia assessment. Pts with normal LV function undergo adenosine, those with moderately-reduced ejection fraction (EF) and wall motion abnormalities high-dose dobutamine, pts with EF35% low-dose dobutamine. All pts undergo late gadolinium enhancement and repeat the same scan at 12 ± 3 months, regardless of PCI success or decision for OMT.A multi-parameter CMR protocol tailored on pts characteristics to study viability/ischaemia could help in identifying responders in terms of LV function, ischaemic burden and clinical outcome among pts suitable for CTO-PCI, improving selection of best candidates to percutaneous revascularization.

Fabry disease (FD) is a rare X-linked inherited lysosomal storage disorder caused by deficient α-galactosidase A activity that leads to an accumulation of globotriasylceramide (Gb3) in affected tissues, including the heart. Cardiovascular involvement usually manifests as left ventricular hypertrophy, myocardial fibrosis, heart failure, and arrhythmias, which limit quality of life and represent the most common causes of death. Following the introduction of enzyme replacement therapy, early diagnosis and treatment have become essential to slow disease progression and prevent major cardiac complications. Recent advances in the understanding of FD pathophysiology suggest that in addition to Gb3 accumulation, other mechanisms contribute to the development of Fabry cardiomyopathy. Progress in imaging techniques have improved diagnosis and staging of FD-related cardiac disease, suggesting a central role for myocardial inflammation and setting the stage for further research. In addition, with the recent approval of oral chaperone therapy and new treatment developments, the FD-specific treatment landscape is rapidly evolving.

Background Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy (HCM). Cardiac magnetic resonance (CMR) detects replacement fibrosis (RF) through late gadolinium enhancement (LGE) and interstitial fibrosis (IF) in apparently unscarred myocardium by T1 mapping-derived increased extracellular volume (ECV). Differently from LGE, to date only few small studies have explored the clinical significance of IF in HCM and a correlation between IF and diastolic dysfunction (DD) has been proposed. However, DD detection is challenging in this population since the accuracy of standard echocardiographic parameters is controversial, especially in presence of left ventricular outflow tract obstruction (LVOTO). Left atrial (LA) dysfunction is associated with high left ventricular (LV) filling pressures and may represent an early marker of DD in HCM. Purpose To explore the correlation between IF and LA dysfunction in HCM patients with preserved systolic function. Methods 93 consecutive HCM patients with preserved EF underwent a standard CMR scan. Semi-automatic threshold-based quantification of ventricular volumes, function and mass was performed. LA volumes (LAV) and function were evaluated by CMR feature-tracking (FT) analysis. The three atrial phasic functions were analyzed: (i) passive strain (εe), (ii) active strain (εa) and (iii) total strain (εs). LGE was quantified using the standard deviations (SDs) method (≥4 SDs). IF was assessed by T1 mapping-derived ECV quantification in remote myocardium (r-ECV). A matched group of 15 healthy subjects (HS) served as controls. Results Compared to HS, HCM patients showed increased LAV (LAV max: HS 39±9ml, HCM 59±20 ml; LAV min: HS 16±4 ml, HCM 34±17 ml; p0.05). HCM patients with increased r-ECV showed significantly impaired LA function in terms of all three strain parameters vs. normal r-ECV group (HCM r-ECV Conclusions In HCM patients increased r-ECV correlates with LA dysfunction, hinting towards a possible role for IF in determining altered LV relaxation and DD. LA strain in controls and HCM ECV groups Funding Acknowledgement Type of funding source: None

Background Cardiac Magnetic Resonance (CMR) allows to detect progressive stages of cardiac involvement in Fabry Disease (FD). A systematic description of electrocardiographic (ECG) alterations occurring in FD is currently missing. Purpose To explore ECG changes in progressive stages of FD cardiomyopathy. Methods 71 FD patients and 17 healthy controls underwent CMR with T1 mapping and 12-lead ECG. ECG analysis included the duration of the P-wave and the interval between the end of P-wave and the beginning of QRS (PendQ). FD patients in the test cohort were divided into 3 groups with increasing severity of cardiac involvement: A) normal T1, no LVH; B) low T1, no LVH; C) low T1, LVH. Results An increase of Pwave/PendQ ratio was observed in Group A compared to Controls (1.08 vs. 0.75, p Conclusion FD is characterized by progressive ECG changes. The identification of ECG parameters able to predict a lowering of myocardial T1 values on CMR may promote early detection of cardiac involvement, helping to target the therapeutic approach. Progressive ECG and CMR changes in FD Funding Acknowledgement Type of funding source: Other. Main funding source(s): This study was partially supported by Ricerca Corrente funding from the Italian Ministry of Health to IRCCS Policlinico San Donato.

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 Differential diagnosis between Anderson-Fabry (AF) and sarcomeric hypertrophic cardiomyopathy (HCM) is often very challenging particularly in AF patients with late onset cardiac involvement. Purpose To gain new insights from standard electrocardiogram (ECG) in AF disease for differential diagnosis from sarcomeric HCM. Additionally, to better understand ECG features in AF patients, a correlation substudy ECG-cardiac magnetic resonance (CMR) has been performed. Methods From 162 patients with definite diagnosis of AF disease, 111 [65 males, median age 57 (51–67) years] with pathologic left ventricular hypertrophy (LVH) (Group A) were compared with 111 sarcomeric HCM patients (Group B) sex, age and maximal wall thickness matched by 1:1 propensity score. Results AF patients showed shorter PR interval [155 (140–180) vs 163 (149–184) msec; p=0.005) and wider QRS interval [110 (100–134) vs 100 (90–106) msec; p Conclusions Compared to matched sarcomeric HCM, AF patients had a shorter PR, wider QRS and a higher percentage of RBBB in relation to to the different aetiology (storage vs “pure” hypertrophy). The higher total QRS score and the absence of inferior Q waves could reflect the more frequent concentric distribution of LVH. Additionally negative T waves, especially in inferior leads, are related to the presence of LGE on CMR (often in the postero-lateral wall). Funding Acknowledgement Type of funding source: None

Aims Fabry cardiomyopathy is characterized by glycosphingolipid storage and increased myocardial trabeculation has also been demonstrated. This study aimed to explore by cardiac magnetic resonance whether myocardial trabecular complexity, quantified by endocardial border fractal analysis, tracks phenotype evolution in Fabry cardiomyopathy. Methods and results Study population included 20 healthy controls (12 males, age 32±9) and 45 Fabry patients divided into three groups: 15 left ventricular hypertrophy (LVH)-negative patients with normal T1 (5 males, age 28±13; Group 1); 15 LVH-negative patients with low T1 (9 males, age 33±9.6; Group 2); 15 LVH-positive patients (11 males, age 53.5±9.6; Group 3). Trabecular fractal dimensions (Dfs) (total, basal, mid-ventricular, and apical) were evaluated on cine images. Total Df was higher in all Fabry groups compared to controls, gradually increasing from controls to Group 3 (1.27±0.02 controls vs. 1.29±0.02 Group 1 vs. 1.30±0.02 Group 2 vs. 1.34±0.02 Group 3; P Conclusion Fabry cardiomyopathy is characterized by a progressive increase in Df of endocardial trabeculae together with shortening of T1 values. Myocardial trabeculation is increased before the presence of detectable sphingolipid storage, thus representing an early sign of cardiac involvement.

Anderson-Fabry disease (AFD) cardiomyopathy is characterized by glycosphingolipid (Gb3) storage in all cellular components, with consequent left ventricular hypertrophy (LVH). Gb3 accumulation also involves atrial myocytes ([1][1]), ultimately leading to left atrial (LA) enlargement and reduced

Post-infarction myocardial scar causes adverse left ventricular remodelling and negatively affects the prognosis. We sought to investigate whether scar extent and location obtained by cardiac magnetic resonance may affect the reverse remodelling and survival of heart failure patients undergoing surgical ventricular reconstruction.From January 2011 to December 2015, 151 consecutive patients with previous myocardial infarction and left ventricular remodelling underwent surgical ventricular reconstruction at our Institution, of which 88 (58%) patients had a preoperative protocol-standardized late gadolinium enhancement (LGE)-cardiac magnetic resonance examination during the week before surgery. We excluded 40 patients with devices (26%), 15 patients with irregular heart rhythm (permanent atrial fibrillation, 10% not included in the device group) or mixed contraindications (severe claustrophobia or presence of material magnetic resonance not compatible). Among the 145 survivors, 11 patients received an implantable cardioverter defibrillator after surgery (mostly for persistent low ejection fraction) and were excluded as well, yielding a total of 59 patients (48 men, aged 65 ± 9 years) who repeated a protocol-standardized LGE-cardiac magnetic resonance examination even 6 months postoperatively and therefore represent the study population. Patients were grouped according to the presence of LGE in the antero-basal left ventricular segments (Group A) or the absence of LGE in the same segments (Group B). The postoperative left ventricular end-systolic volume index was considered the primary end-point.After surgery, left ventricular end-systolic volume index and end-diastolic volume index significantly decreased (P 0.001, for both), while diastolic sphericity index and ejection fraction significantly increased (P = 0.015 and P 0.001, respectively). The presence of LGE in the antero-basal left ventricular segments (10 patients, Group A) was the only independent predictor of outcome (P = 0.02) at multivariate analysis, being the postoperative left ventricular end-systolic volume index significantly higher compared to that of patients of Group B (49 patients) (78 ± 26 ml/m2 vs 55 ± 20 ml/m2, P = 0.003). Furthermore, patients with a postoperative left ventricular end-systolic volume index60 ml/m2 showed a higher risk of cardiac events (hazard ratio = 3.67, P = 0.02).In patients undergoing surgical ventricular reconstruction, LGE scar location affects the left ventricular reverse remodelling, which in turn might limit the survival benefit.

Background Heart involvement represents the main cause of death in Fabry Disease (FD), thus its early detection is important to define the optimal therapeutic strategy. Recently, a disproportionate increase in myocardial trabeculation has been described in FD by cardiac magnetic resonance (CMR), even in early (prehypertrophic) stage of the disease. In addition, CMR with T1 mapping can identity the presence of myocardial sphingolipid storage (causing lowering of native T1 values) in more than 50% of FD patients with no LVH. However, it is not clear whether a relationship exists between trabecular complexity and sphingolipid storage in FD. Aim To explore the association between myocardial trabecular complexity, quantified by endocardial border fractal analysis, and sphingolipid storage, described by CMR T1 mapping, in different stages of Fabry cardiomyopathy. Methods Study population included 60 subjects: 15 FD patients with no detectable signs of cardiac involvement (no LVH, normal T1; 2 M, age 30.6±14; Group 1); 15 FD patients with early sphingolipid storage (no LVH, low T1; 9 M, age 33±9.6; Group 2); 15 FD patients with LVH (11 M, age 53.5±9.6; Group 3); 15 healthy controls (9 M, age 34±10). Patients and controls underwent CMR with T1 mapping; disease severity was quantified using Mainz Severity Score Index (MSSI). Myocardial trabecular fractal dimension was evaluated, blinded to patients'characteristics, on short axis cine images using the Image J dedicated plug-in FracLac, deriving the following parameters: total, basal, mid-ventricular and apical fractal dimensions. Results Total fractal dimension was higher in all Fabry groups compared to controls. Indeed, a gradient of total fractal dimension was observed, with this parameter gradually increasing from healthy controls to Groups 3 (1.27±0.02 in controls vs 1.29±0.02 in Group 1 vs 1.30±0.02 in Group 2 vs 1.34±0.02 in Group 3; p Conclusion Cardiac involvement in FD is characterized by a progressive increase in fractal dimension of endocardial trabeculae (Figure 1C). Both total and basal myocardial trabeculation are increased in Fabry patients even before the presence of detectable sphingolipid storage, thus representing a very early sign of cardiac involvement.