Abstract Background Cardiac involvement in Fabry Disease (FD) manifests as left ventricular hypertrophy (LVH) often complicated by myocardial fibrosis and/or inflammation. Both LVH and advanced tissue alterations can be non-invasively detected and quantified by cardiac magnetic resonance (CMR) with Late Gadolinium Enhancement (LGE). Impairment in functional capacity has been previously reported in FD patients. However, there is limited data regarding the determinants of myocardial alterations in exercise intolerance in FD. Methods Among 190 consecutive FD patients referred for CMR, 41 simultaneously performed a cardiopulmonary exercise test (CPET) to evaluate functional capacity. All patients underwent an extensive CMR protocol to provide a detailed evaluation of cardiac morphology and function, including multiparametric tissue characterization. CPET parameters were compared between patients with advanced Fabry cardiomyopathy (Group B), characterized by hypertrophy, inflammation, and fibrosis, and FD patients without irreversible cardiac damage (Group A). Results Group B patients were older compared to Group A (57.0 years vs 33.5 years, p<0.001), had a greater LVH (LVMI: 117 g/sqm vs 76.5 g/sqm, p<0.001; LVMWT 17 vs 10 mm, p<0.001). LV ejection fraction was preserved in both groups but Group B patients had a lower peak VO2 value compared to group A (17.8 ml/kg/min vs 21.9 ml/kg/min, p=0.025), a lower (but not significant) percent-predicted peak VO2. A negative linear correlation was identified between the LGE extension (expressed as % of LV mass) and peak VO2 (r=-0.553, p=0.014). This correlation remained consistent even after excluding patients under chronic beta-blocker therapy (r=-0.678, p=0.045). No significant correlation between LV mass and peak VO2 was found. Conclusions in patients with FD, the presence of advanced tissue alterations detected by LGE is associated with reduced functional capacity (low peak VO2) despite preserved LV ejection fraction, with a significant negative correlation.

Abstract Background The role of cardiopulmonary exercise test (CPET) in hypertrophic cardiomyopathy (HCM) has been previously examined, revealing two prognostic parameters: peak Vo2 and the VE/VCO2 slope. Specifically, individuals with a VE/VCO2 value above 31 (ventilator inefficiency) demonstrate a poorer prognosis. Purpose This study aims to analyze the physiological factors contributing to ventilatory inefficiency in individuals with HCM. Methods In this retrospective study, 43 patients HCM patients underwent resting transthoracic echocardiography, CPET combined with echocardiography during physical exertion, and cardiac magnetic resonance imaging. Ventilatory inefficiency was defined as a VE/VCO2 slope exceeding 31, leading to the identification of two groups: Group A (those with ventilatory inefficiency) and Group B (those without ventilatory inefficiency). Results Nine patients exhibited ventilatory inefficiency, while 34 had a normal VE/VCO2 slope. No statistically significant differences were found between the two groups concerning clinical and therapeutic characteristics. Subjects with ventilatory inefficiency showed reduced oxygen pulse (8.3 ± 2.6 vs 11.7 ± 4, p 0.013) and peak VO2 values (13 ± 5 vs 19 ± 5, p 0.005), lower left ventricle global longitudinal strain (-15±3 vs -17± 2, p 0,012), the exertional TAPSE/SPAP ratio (0.46 [0.32-0.48] vs 0.58 [0.47-0.80], p 0.001), exertional TAPSE (23 ± 3 vs 28 ± 4, p 0.001), and indexed stroke volume of the left ventricle assessed by cardiac magnetic resonance imaging (38±8 vs 48±10, p 0.011) (Table 1). The right ventricular function under physical exertion (peak TAPSE and TAPSE/sPAP) and left ventricular functional parameters (index stroke volume and global longitudinal strain) predicted the presence of ventilatory inefficiency. Conclusions This study highlights the role of exertional parameters in the origin of ventilatory inefficiency.Correlation tableFigure with scatter plot

Abstract Background Considerable data are available concerning improvements in diagnostic approaches over recent years for the treatment of heart failure with reduced ejection fraction (HFrEF). Conversely, regarding heart failure with preserved ejection fraction (HFpEF), there has been relatively little change in terms of therapy and prognostic stratification. Many efforts have been made to phenotype HFpEF spectrum, aiming to identify simple and reliable tools for recognizing patients at high risk for mortality. Purpose The aim of the present study is to identify a prognostic tool for all-cause mortality in patients with HFpEF. Methods From 2013 to 2024 thirty-eight HFpEF patients who underwent both transthoracic echocardiography at rest and cardiopulmonary exercise test (CPET) combined with echocardiography have been enrolled. Patients with established cardiomyopathy, such as hypertrophic cardiomyopathy and cardiac amyloidosis, have been excluded from the analysis. Mean follow-up period was 3,7 years. Primary outcome was all-cause mortality. Results Sixteen patients (42%) died during the study's follow-up period. No statistically significant differences were found for clinical, demographic, and therapeutic variables. Among all echocardiographic parameters, both at rest and during exertion, E/e' at rest (12 [8.9-19] vs. 17 [12-33], p-value 0.023), SPAP at rest and during exertion (31 ± 7 vs. 43 ± 16, p-value 0.021 and 51 ± 10 vs. 66 ± 17, p-value 0.019), TAPSE/SPAP at rest and during exertion (0.67 ± 0.15 vs. 0.47 ± 0.20, p-value 0.005 and 0.48 ± 0.15 vs. 0.33 ± 0.12, p-value 0.019), and left atrial reservoir function (22 [15-29] vs. 9.4 [6-15], p-value 0.001) were significantly associated with all-cause mortality (Table 1). Among CPET variables, respiratory exchange rate and oxygen pulse were associated with all-cause mortality (1.1 ± 0.13 vs. 1.18 ± 0.15, p-value 0.021 and 10 [7-11] vs. 8.1 [5.4-8.7], p-value 0.008) (Table 1). In multivariate analysis, the only independent predictor of mortality was left atrial reservoir function (p-value 0.026, OR 1.17 [1.02-1.35]). The optimal cutoff was identified using the Youden Index analysis (cut-off: 16.4%, sensitivity 85%, specificity 68%; AUC 0.839 [0.710-0.969]) (Figure 1). Survival curves based on the optimal cutoff are reported in Figure 1. Conclusions In a cohort of patients with HFpEF the left atrial reservoir function remains an important prognostic determinant for all-cause mortality. These results highlight the importance of estimating left ventricular filling pressures which are higher in patients diagnosed with HFPEF due to diminished ventricular compliance. Further studies with a larger cohort are needed to confirm these preliminary data.

Abstract Background Cardiac magnetic resonance (CMR) characterization of myocardial tissue is routinely used in clinical practice. Compared to traditional CT, Photon counting CT (PCCT) uses photon-counting detectors offering higher spatial resolution, elimination of electronic noise and improved contrast-to-noise ratio. A comparison between CMR and PCCT for myocardial characterizazion in an urgent setting, however, has not yet been explored. Purpose The aim of this study was to compare the ability to characterize myocardial tissue between PCCT and CMR in patients presenting with acute chest pain in the emergency department (ED). Methods This single-center prospective study enrolled all consecutive patients presenting to the ED of our hospital from November 2023 to January 2024 with chest pain, ECG alterations and troponin rise consistent with myocardial injury. Patients needing urgent coronary angiography according to guidelines were excluded. PCCT was performed urgently for triple rule-out, but also for tissue characterization through post-iodine-contrast administration images. Within 24 hours, all patients underwent a CMR protocol including T2-weighted and late gadolinium enhancement (LGE) images for tissue characterization. Results Six male patients with a mean age of 20 ± 10 years were enrolled. All clinical, PCCT, and CMR parameters are presented in Table 1. All patients presented with diffuse ST-segment elevation and exhibited T2-weighted images (for edema detection) and LGE distribution (subepicardial and intramyocardial) consistent with acute myocarditis. Mean radiation exposure for PCCT was 0.8±0.1 mSv. A strong linear correlation emerged between PCCT-derived delayed enhancement (DE) volume and CMR-derived late gadolinium enhancement (LGE) volume (r = 0.970; p value 0.001) (Table 1). Similar results were achieved when comparing the number of DE and LGE myocardial segments (r = 0.871; p value 0.026). Significant correlations also emerged between DE, LGE, and high-sensitive troponin (hsTN) at presentation (respectively: PCCT-DE vs hsTN r = 0.951, p value 0.004; CMR-LGE vs hsTN r = 0.918, p value 0.010). CMR showed a much higher signal-to-noise ratio (SNR) for the delayed enhanced myocardium and contrast-to-noise (CNR) ratio between the delayed enhanced and normal myocardium with respect to PCCT in post-contrast images (respectively 7.4 ± 3.9 vs 27.2 ± 17.7, p value 0.024 and 5.5 ± 3.7 vs 38.8 ± 30.2, p value 0.023). In T2-weighted images both SNR for the hyperintense myocardium (30.3 [20.4-122.4]) and CNR between the hyperintense and normal myocardium (26.7 [13.3-60.2]) resulted to be higher compared to PCCT (p value 0.027 and 0.045, respectively) (Table 1). Conclusions PCCT appears to be reliable when compared to CMR for detecting myocardial edema through the acquisition of post-contrast images in the acute setting with an acceptable CNR.

Abstract Background Despite different etiopathogenesis, Fabry disease (FD) cardiomyopathy and sarcomeric hypertrophic cardiomyopathy (HCM) share a similar hypertrophic phenotype. Cardiac magnetic resonance (CMR) plays a pivotal role in distinguishing between these two clinical conditions, thanks to the thorough morphological definition of the phenotype and non-invasive tissue characterization. A high prevalence of mitral apparatus anomalies has been previously described both in sarcomeric HCM and FD cardiomyopathy. Purpose This study systematically compares the morphology of the mitral apparatus in sarcomeric HCM and FD cardiomyopathy, to add new insights into differential diagnosis. Methods CMR images of 120 patients were retrospectively analyzed and divided as follows: healthy controls CTRL (n=40), HCM (n=40), and FD (n=40) with left ventricular hypertrophy (LVH). The analyses included the measurement of I) papillary muscles’ hypertrophy, expressed as the maximum diameter (D max) of the anterolateral (AL) and posteromedial (PM) papillary muscles (see Figure 1 A and B); II) the anteriorization of the anterolateral papillary muscle defined as the distance between the anterolateral papillary muscle and the anterior interventricular junction (Anteriorization of AL) (Fig. 1 C); III) the length of the anterior mitral leaflet (MVL length) (Fig. 1 D). All measurements were performed on cine-SSFP sequences in diastole. Results Compared to healthy controls, HCM and FD patients showed significant hypertrophy of both papillary muscles (p<0.001) and elongation of the anterior mitral leaflet (p<0.001). Both papillary muscles in FD patients showed greater hypertrophy compared to HCM patients (D max AL p=0.017 and D max PM p=0.039). No significant differences were observed between FD and HCM regarding MVL length (p=0.078). Compared to FD (p=0.028) and healthy controls (p<0.001), HCM patients showed greater anteriorization of the anterolateral papillary muscle. (Results are summarized in Table 1). Conclusions From the comparison of mitral valve apparatus anomalies between HCM and FD, it emerged that patients with FD cardiomyopathy show a higher degree of papillary muscle hypertrophy, while patients with sarcomeric HCM display a greater anterior displacement of the anterolateral papillary muscle. The systematic analysis of the morphology of mitral apparatus can be integrated in the differential diagnosis between these two pathologies.Fig.1 Representation of MeasurementsTable 1.Summary results table

Abstract Funding Acknowledgements Type of funding sources: None. Background Despite prompt reperfusion and optimal medical therapy of acute ST-elevation myocardial infarction (STEMI), patients may undergo left ventricular (LV) remodeling (REM), which may lead to systolic and/or diastolic heart failure. Little is known regarding factors and mechanisms leading to LV REM, and this knowledge gap hinders potential strategies to prevent this complication. Left atrium (LA) functional and dimensional parameters are emerging as independent prognostic markers in ischemic heart disease. Purpose The present study aims at exploring the potential role of LA morpho-functional parameters by CMR-FT in predicting LV REM following STEMI. Methods This study derives from a sub-analysis of the prospective and multicenter "VavirimS" trial. All patients were assessed through 2 consecutive CMR scans, at 1 and 6 months after STEMI. CMR-FT was applied to both LA and LV. The endpoint was to evaluate the association between LA volumes and phasic functions with LV REM at 6-month follow up, defined as: i) LV REMEDV: ≥10% increase in LV end diastolic volume (EDV); ii) LV REMEDV-ESV: ≥12% increase in LV EDV and ≥6% LV end systolic volume (ESV). Results Out of 193 patients included in the VavirimS trial, 149 were enrolled and 44 have been excluded either for inadequate image quality for CMR-FT analysis or for the presence of factors impacting on LA morphology and function (i.e. mitral regurgitation and atrial fibrillation). LV REMEDV occurred in 34 patients (23%), who showed worse LA strain parameters (reservoir, conduit and booster function), LV global radial strain (GRS) and LV global circumferential epicardial strain [Fig. 1]. At multivariate analysis, LA reservoir and LV global radial strain (GRS) were confirmed as independent predictors of LV-REMEDV [Fig. 1]. The best cut-off for LA reservoir and LV GRS were 20% (sensitivity 97%; specificity 45%) and 56% (sensitivity 67%; specificity 69%), respectively. LV REMEDV-ESV occurred in 17 patients (11%), who showed reduced LA strain and LV GRS [Fig. 1]. The only independent predictor of LV remodeling in this group was LA reservoir [Fig. 1]. A subgroup analysis has been performed on two groups, according to EF: i) p-EF: preserved ejection fraction, ii) r-EF: reduced ejection fraction. In the p-EF group both LA reservoir and LV GRS were confirmed to be associated with LV REM [Fig. 1], while in the r-EF group the only independent predictor of LV REM was LV GRS [Fig. 1]. Conclusions CMR-derived LA reservoir and LV GRS are independent predictors of LV remodeling following STEMI. In patients with preserved EF LA reservoir is confirmed as independent predictor of LV remodeling, hinting at early and subclinical impairment of left chambers compliance. LA functional parameters following STEMI may help physicians in identifying patients at higher risk of LV remodeling.

Abstract Funding Acknowledgements Type of funding sources: None. Background Myocardial viability assessment can guide myocardial revascularization in patients with coronary artery disease. Non-invasive imaging modalities are routinely used for detection of viable myocardium and the highest diagnostic performance is provided by Cardiac Magnetic Resonance (CMR): it combines high sensibility (95%) by delayed enhancement (DE) assessment and high specificity (91%) by evaluation of myocardial systolic thickening recovery at increasing dose of dobutamine (Db-systolic recovery). Purpose Identification of independent predictors for Db-systolic recovery of akinetic segments supplied by a chronic total occlusion (CTO) coronary artery. The second purpose was to develop a diagnostic tool as alternative to dobutamine stress imaging to provide an estimation of myocardial response to inotropic agents. Methods This single center prospective observational study enrolled 47 consecutive patients referred to CMR for evaluation of inducible ischemia and myocardial viability in the territory of one or more CTOs. All enrolled patients presented basal akinetic segments in the CTO territory. Cine-Steady State Free Precession (SSFP) sequences were acquired both in basal and at increasing dose of dobutamine to evaluate Db-systolic recovery. Stress perfusion imaging and DE were then acquired to detect inducible ischemia and necrotic areas. Post-processing CMR-Feature Tracking strain analysis provided both radial and circumferential strain on basal, mid and apical short axis planes. Results Table 1 lists clinical characteristics of the study population. A total of 189 akinetic segments supplied by a CTO were detected and divided into viable and non-viable groups according to their ability to recover or not at increasing dose of dobutamine, respectively. Parameters of each akinetic segment significantly (p value < 0.05) associated with viability at univariate analysis were included in the multivariable binary logistic regression to identify independent predictors of Db-systolic recovery (Table 2). These independent predictors have been then included in a logistic regression model as continuous variable except for Transmural Extent of DE which can be either 1 or 0 according to DE<75% or ≥75%, respectively: L= −5.459 + 0.033 * (Radial Peak Systolic Strain) + 0.067 * (Circumferential Endocardial Peak Systolic Strain) + 1.808 * (Transmural Extent of DE) + 0.358 * (Diastolic Wall Thickness). When L ≥ 0 the model predicts contractile recovery during dobutamine infusion with an accuracy of 83.1%. Conclusion This CMR prospective study identifies independent predictors of contractile recovery at increasing dose of dobutamine and provides a diagnostic tool which might substitute dobutamine assessment with a good accuracy, reducing acquisition time and adverse events in patients with CTOs. An external validation study is needed to assess the consistency of this model for clinical purposes.

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac involvement in Fabry Disease (FD) manifests as left ventricular hypertrophy (LVH) often complicated by myocardial fibrosis and/or inflammation. Indeed, glycosphingolipid storage does not explain the whole spectrum of FD pathophysiology. Lysosomal deposits of unmetabolized glycolipid substrates stimulate the activation of immunological pathways, taking to a chronic inflammatory process.1 In a subgroup of FD patients with late gadolinium enhancement (LGE), signs of myocardial inflammation can be detected by cardiac magnetic resonance (CMR) using T2-weighted (T2w) sequences and T2 mapping. T2 value in inferolateral wall (IL) has been described as the strongest predictor of increase in troponin level. 2 Aim The aims of the study were: 1) to compare CMR parameters in LVH and LGE positive FD patients with and without myocardial inflammation; 2) to verify if myocardial inflammation plays an incremental prognostic role in FD compared to LVH and LGE. Methods Among 190 consecutive FD patients referred for CMR, 47 patients with LVH and LGE were selected for this study. All patients underwent an extensive CMR protocol to provide a detailed evaluation of cardiac morphology and function, with multiparametric tissue characterization. Myocardial inflammation was detected by T2w and T2 mapping sequences. A comparison of CMR parameters between patients with and without inflammation was performed. A composite endpoint of cardiovascular (CV) events was used for survival analysis. Results No differences in age and Mainz Severity Score Index were found between LVH+/LGE+ FD patients with and without myocardial inflammation. Patients with inflammation showed significantly greater left ventricular mass index (LVMI) compared to patients without inflammation. Regarding tissue characterization, patients with myocardial inflammation had more extensive LGE and significantly higher ECV in IL wall. Native myocardial T1 was reduced in both groups without statistically significant difference. (Table 1) Myocardial inflammation always involved IL wall. During a median follow-up of 30 months, Kaplan-Meier curves showed similar event-free survival probability in patients with and without myocardial inflammation (Log-Rank p = 0,215, Figure 1). Conclusion In a population of LVH+/LGE+ FD patients, the presence of CMR signs of myocardial inflammation was associated with more severe LVH and more extensive LGE. However, the presence of myocardial inflammation did not showed an incremental prognostic value on CV outcomes on top of LVH and LGE. Larger studies are needed to verify this findings.

Background: Well-developed collaterals are assumed as a marker of viability and ischemia in chronic total occlusions (CTO). We aim to correlate viability and ischemia with collateral presence and extent in CTO patients by cardiac magnetic resonance (CMR). Methods: Multicentre study of 150 CTO patients undergoing stress-CMR, including adenosine if normal systolic function, high-dose-dobutamine for patients with akinetic/>2 hypokinetic segments and EF =35%, otherwise low-dose-dobutamine (LDD); all patients underwent late gadolinium enhancement (LGE) imaging. Viability was defined as mean LGE transmurality <= 50% for adenosine, as functional improvement for dobutamine-stress-test, ischemia as >= 1.5 segments with perfusion defects outside the scar zone. Results: Rentrop 3/CC 2 defined well-developed (WD, n = 74) vs poorly-developed collaterals (PD, n = 76). Viability was equally prevalent in WD vs PD: normo-functional myocardium with <= 50% LGE in 52% vs 58% segments, p = 0.76, functional improvement by LDD in 48% vs 52%, p = 0.12. Segments with none, 1-25%,26-50%,51-75% LGE showed viability by LDD in 90%,84%,81%,61% of cases, whilst in 12% if 76-100% LGE (p < 0.01). There was no difference in WD vs PD for ischemia presence (74% vs 75%, p = 0.99) and extent (2.7 vs 2.8 segments, p = 0.77). Conclusions: In a large cohort of CTO patients, presence and extent of collaterals did not predict viability and ischemia by stress-CMR. Scar extent up to 75% LGE was still associated with viability, whereas ischemia was undetectable in 25% of patients, suggesting that the assessment of CTO patients with CMR would lead to a more comprehensive evaluation of viability and ischemia to guide revascularization.

Abstract Funding Acknowledgements Type of funding sources: Private hospital(s). Main funding source(s): This work was supported by IRCCS Policlinico San Donato, a Clinical Research Hospital partially funded by the Italian Ministry of Health. Introduction Blood flowing into the left ventricle (LV) forms a 3D vortex ring starting from the free margin of mitral valve leaflets and encompassing the inflow jet. Vortex ring formation is presumed to store part of the kinetic energy of the entering jet and help directing blood flow towards the aorta [1]. Changes in vortex formation are associated to altered endocardial wall motion and LV chamber remodeling, as in case of ischemic cardiomyopathy (ICM). 4D Flow MRI is currently the unique volumetric imaging technique to assess in vivo changes of diastolic vortex ring. Purpose To characterize changes in LV diastolic vortex ring and associated energetics in a cohort of ICM patients (n = 12) vs. controls (n = 12) with comparable age. Methods 4D Flow MRI data were acquired for ICM patients presenting with anterior myocardial infarction and in healthy controls. The diastolic vortex ring was assessed at peak E-wave and at peak A-wave through the λ2 method [2]. Geometrical features of the vortex ring, e.g., circularity index (CI) and vortex orientation (α), were extracted (Figure 1). Kinetic energy (KE), rate of viscous energy loss (EL), vorticity and volume were computed for each vortex ring core; the ratios with the respective quantities computed for the entire LV were derived. Results At peak E-wave, the vortex ring was less circular (p = 0.017) and formed a smaller α with the mitral valve plane (p = 0.024) in ICM patients as compared to controls. At peak A-wave, the vortex ring core remained less circular (p = 0.027) in ICM patients, while vortex orientation remained comparable between the two groups. KE ratio, EL ratio, vorticity ratio and volume ratio significantly decreased for ICM patients at both E-peak and A-peak (Table 1). Conclusions Though ICM is primarily addressed and investigated as a systolic dysfunction, diastolic function can be deranged too, as highlighted by altered diastolic vortex ring shape and energetics.

Abstract Funding Acknowledgements Type of funding sources: None. Background Fabry disease (FD) is an X-linked lysosomal storage disorder due to a deficiency/absence of alfa-galattosidase A enzyme activity. More than 1000 GLA gene mutations have been identified to be causative of classical or late-onset clinical phenotype. Cardiac variants (p.N215S, p.F113L and IVS4+919G>A) cause a predominant late-onset cardiac involvement with minimal systemic manifestations compared to classical phenotype.1 Cardiac magnetic resonance (CMR) is widely used to assess FD cardiac involvement, thanks to its accuracy in quantification of left ventricular mass and to the possibility to perform a non-invasive tissue characterization.2 Since cardiac involvement is the main cause of FD morbidity and mortality,3 CMR findings play a prognostic role in FD. Purpose the aims of this study were: 1) to compare CMR phenotypes of FD patients with classical and cardiac variant of the disease; 2) to compare the prognostic role of CMR parameters in these two groups of FD patients. Methods study population included 128 FD patients (classical variant: 69%, cardiac variant 31%). Clinical characteristics and CMR findings were compared between classical and cardiac variant. CV events during follow-up were abstracted from the patients’ records and only first event after CMR was used for survival analysis. The composite endpoint was defined as the development of one of the following events: a) sustained or non-sustained ventricular tachycardia, b) bradyarrhythmias requiring pacing, c) heart failure hospitalization, d) atrial fibrillation, e) myocardial infarction and f) all-cause mortality. Results compared to patients with cardiac variant, FD patients with classical mutations were younger (39 [26–53] vs 46 [37–57], p = 0,050), with a more severe systemic involvement according to Mainz Severity Score index (MSSI: 20,50 [9,25–27,00] vs 9,00 [2,00–23,00], p = 0,003). Overall, 37% (48/130) of patients assumed FD specific treatment, most of them exhibiting a classical mutation (43/48 patients, p<0,001).No significant differences in CMR parameters were observed comparing the two groups of patients. The percentage of patients with LVH, LGE and low T1 values were similar in classical and cardiac variants. During a median follow-up of 36 [17–57] months, Kaplan Meier curves shows a similar event-free survival probability (Log-rank p = 0,362) between the two phenotypes (Fig. 1). In addition, presence of LVH and LGE were both associated with composite CV endpoint in these two groups of patients. Conclusion patients with cardiac variants of FD showed similar CMR phenotype and CV prognosis compare to patients with classical mutations. The presence of LVH and LGE play the same prognostic impact in both the clinical phenotypes. CMR assessment of cardiac involvement represents a pivotal step in the evaluation of FD patients irrespective of patients’ genotype.

Abstract Background congenital corrected transposition of great arteries (ccTGA) leads to systemic position of the right ventricle (sRV). Patients with ccTGA are usually asymptomatic in the first decades of life but over time sRV will fail to support elevated systemic pressure, possibly leading to systolic heart failure (HF) in adulthood. Several factors have been associated with sRV failure and worse prognosis such as tricuspid valve dysfunction, conduction abnormalities, previous surgery due to associated lesions. However, little is known about diastolic function in sRV. We hypothesize that diastolic dysfunction characterizes sRV pathophysiology, therefore an accurate evaluation of diastolic function would allow a better assessment and risk stratification of patients. The present study aims to investigate the diastolic function in patients with ccTGA by assessing left atrial (LA) morpho-functional parameters. Methods we retrospectively examined Cardiac Magnetic Resonance (CMR) imaging of 33 ccTGA patients clinically referred to our Center between April 2014 and December 2022. ccTGA patients were matched based on sex and age with a healthy volunteer population (control group) and a group of patients with Hypertrophic Cardiomyopathy (HCM) diagnosed with HFpEF according to HF guidelines criteria. LA morpho-functional parameters were compared among the three groups: LA volumes (obtained by the length-area method), ejection fraction (EF) and, by means of feature tracking analysis, strain reservoir (εs), conduit (εe) and booster pump (εa). All patients were in sinus rhythm at the time of CMR. Results In comparison with the control group, ccTGA patients had a significant impairment in LA function (LA EF: 41,6 ± 15,1 vs 63,9 ± 7,8, p < 0,001, εs: 19,0 ± 8,3 vs 38,0 ± 10,3, p < 0,001, εe: 11,7 ± 5,9 vs 21,1 ± 8,3 p < 0,001, εa: 7,6 ± 4,1 vs 16,8 ± 6,1, p < 0,001). Conversely, no significant difference was found between ccTGA and HCM group regarding LA function (EF: 41,6 ± 15,1 vs 42,0 ± 10,1, εs: 19,0 ± 8,3 vs 22,6 ± 8,8, εe: 11,7 ± 5,9 vs 12,6 ± 7,0, εa: 7,6 ± 4,1 vs 10 ± 3,7). As for morphological parameters, ccTGA patients had an increase of LA volumes compared to both the control group and HCM patients. Conclusion ccTGA patients present an impaired LA function and a significative increase in LA volume consistent with the presence of diastolic disfunction. Further studies are needed to assess the clinical impact of morpho-functional LA impairment in ccTGA patients.

Abstract Background Left atrial (LA) volume and function have shown prognostic value in several cardiac conditions. Routine cardiac magnetic resonance (CMR) evaluation of the LA is obtained from standard 2- and 4-chamber long-axis cine images focused on the left ventricle. Previous echocardiographic data showed that LA-focused apical views provide a more accurate estimation of LA maximum volume, as compared to standard apical images. CMR LA-focused imaging could improve the accuracy of LA morpho-functional analysis. CMR feature-tracking (CMR-FT) analysis is emerging as a feasible semi-automatic tool for the evaluation of LA volumes and function. Purpose To investigate the potential of LA-focused CMR cine images using LA CMR-FT analysis. Methods 100 consecutive patients clinically referred to CMR were included in this prospective, observational, multicenter study. LA volumes (LAVmax, LAVmin), emptying fraction (EF), atrial strain reservoir (ɛs), conduit (ɛe), booster (ɛa) and strain rate reservoir (SRɛs) were calculated by CMR-FT analysis on both standard and LA-focused 2- and 4-chamber long-axis cine images. Manual segmentation of a short-axis cine stack covering the LA was used as the reference method (RefMeth) for LA volumes and EF. Results In comparison to the RefMeth, the standard acquisitions underestimated LA volumes (LAVmax: bias = −8ml, LOA = +20, −35ml; LAVmin: bias = −6 ml, LOA = +15, −27ml) and slightly overestimated EF (bias = +3%, LOA = +17, −11%). Conversely, LA-focused images provided a more accurate estimation (LAV max bias = −1ml, LOA = +11, −9ml; LAV min bias = −2ml, LOA = +12, −7ml) and EF (bias = −2%, LOA = +9, −12%). All three LA strain (εs: bias 7%, LOA = 25, −11%; εe: bias 4%, LOA = 15, −8%; εa: bias 3%, LOA = 14, −8%) and SRεs (bias 0.2 s–1, LOA = 1.13, −0.7 s–1) were significantly higher in standard vs LA-focused images (all p<0.001). Conclusions Assessment of LA volumes using CMR-FT applied to dedicated LA-focused long-axis cine images is more accurate than the use of standard acquisitions. LA strain and SRɛs obtained from LA-focused images are significantly lower than those obtained from standard LA acquisitions, possibly due to the inclusion in LA-focused images of LA posterior wall, where pulmonary veins convey and atrial deformation is blunted. Funding Acknowledgement Type of funding sources: None.

Abstract 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 < 0.01). 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.

Abstract 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.

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. To quantify 4D Flow intracardiac kinetic energy (KE) and viscous energy loss (EL) and investigate their relation with LV dysfunction and remodelling. 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<40%). 10 controls were used for comparison. LV was semi-automatically segmented using short axis CMR stacks and co-registered with 4D Flow. Global KE and EL were computed over the cardiac cycle. NT-proBNP measurements were correlated with average and peak values, during systole and diastole. Both LV volume and EF significantly differ (P<0.0001) between iDCM (EDV=294±56 ml, EF=24±8%), ICM (EDV=181±32 ml, EF=34±6%) and controls (EDV=124±29 ml, EF=72±5%). If compared to controls, both ICM and iDCM showed significantly lower KE (P≤0.0008); though lower than controls, EL was higher in iDCM than ICM. Within the iDCM subgroup, diastolic mean KE and peak EL reported good inverse correlation with NT-proBNP (r=−0.75 and r=−0.69, respectively). EL indexed (ELI) to average KE during systole was higher in the entire ischemic group as compared to controls (ELI(ischemic) = 0.17 vs. ELI(controls) = 0.10, P=0.0054). 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. Type of funding source: Public grant(s) – National budget only. Main funding source(s): Italian Ministry of Health

Abstract Background 3D echocardiography has recently revealed alterations of right ventricular (RV) function in Brugada syndrome (BrS) during ajmaline challenge (AC). Cardiac magnetic resonance (CMR) is the gold standard for functional and anatomical RV assessment. CMR feature-tracking (FT) analysis is able to detect subtle functional changes in the underlying myocardial substrate. Purpose To investigate RV functional changes during AC in BrS patients using CMR-FT analysis. Methods 24 consecutive BrS and 28 matched controls underwent CMR. CMR protocol included paraxial and parasagittal cine bSSFP sequences, acquired before and 2÷5 minutes after ajmaline infusion (1 mg/kg in 5 minutes), to obtain a comprehensive evaluation of the RV free wall. All patients were closely monitored with ECG. Semi-automatic threshold-based quantification of ventricular volumes, function and mass was performed in QMass. CMR-FT analysis of RV function was performed in QStrain. Values of longitudinal strain (LS) and transverse displacement (TD) of the RV wall before and after AC were compared in BrS patients and in the control group. Results AC induced Type 1 ECG pattern in all BrS patients and no ECG changes in controls. In BrS patients TD of the RV free wall was significantly reduced (P≤0.003) at peak ajmaline effect; controls reported sub-millimetric TD changes. LS of the RV wall was significantly impaired in BrS patients (P<0.0001) on both b SSFP sequences; LS remained comparable (P=0.62) in controls on the parasagittal sequence; minor but not negligible (P=0.01) LS changes were noticed on the paraxial stack. (Table 1) Conclusions In patients with BrS CMR-FT analysis during AC unveils dysfunctional RV wall mechanics in areas generally associated with abnormal electrical activity. TD and LS in a Brs patient post AC Funding Acknowledgement Type of funding source: None

Abstract 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; p<0.001), reduced LA EF (HS 61±3%, HCM 45±12%, p<0.001), impaired εs (HS 40±7%, HCM 29±11%, p<0.001) and εe (HS 26±7%, HCM 15±7%, p<0.001). No differences in εa were observed (HS 13±4%, HCM 14±7%, p 0.56). HCM patients were divided into 2 groups according to the presence of IF, defined as r-ECV values ≥29%. The two ECV groups did not differ in terms of LV EF, LA EF, LAV, LA area, E/E', LGE, LV mass, maximal wall thickness and LVOTO (all p>0.05). 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 <29%: εs 31±12%, εe15±7%, εa 15±5%; HCM r-ECV≥29%: εs 24±7%, εe 12±4%, εa 12±5%; all p<0.05). 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

Ivabradine is an effective treatment for angina in patients with stable coronary artery disease (CAD) and for heart failure. Experiments in a canine model have shown that ivabradine reduces both acute left ventricular (LV) dysfunction and post-ischaemic stunning. Aim of this study was to investigate the effect of ivabradine on LV dysfunction and stunning in patients with CAD and exercise-inducible ischaemia. Fifteen patients with ejection fraction >40 % and heart rate >70 bpm were enrolled. After pharmacologic washout, echocardiography was performed at rest, at peak treadmill exercise and during recovery until return to baseline. After 2 weeks of ivabradine (7.5 mg bid) stress echocardiography was repeated at the same workload achieved during washout. Peak global and segmental (ischaemic vs. remote normal segments) LV longitudinal strain (LS) was assessed by 2D speckle tracking analysis. At washout, LS was significantly impaired in ischaemic compared to remote segments at peak stress and for several minutes during recovery. After ivabradine a smaller, albeit still significant, impairment of LS in ischaemic segments was observed at peak whilst no difference with remote segments was present during recovery. Furthermore, the average global LS value improved significantly after treatment. In conclusion, ivabradine reduces both acute LV dysfunction and stunning in patients with CAD and exercise-inducible ischaemia. We hypothesise that this mechanism might contribute to reduce chronic LV dysfunction in patients with CAD. In this setting the drug might limit the development of hibernating myocardium which is believed to result from repeated episodes of ischaemia and stunning.