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Aims: transthyretin amyloid cardiomyopathy (ATTR-CM) is predominantly diagnosed in men. The few available studies suggest affected women have a more favourable cardiac phenotype. We aimed to characterize sex differences among consecutive patients with non-hereditary and two prevalent forms of hereditary (h)ATTR-CM diagnosed over a 20-year period. Methods and results: analysis of deep phenotyping at presentation, changes on serial echocardiography and overall prognosis were evaluated. In total, 1732 consecutive patients were studied, comprising: 1095 with wild-type (wt)ATTR-CM; 206 with T60A-hATTR-CM; and 431 with V122I-hATTR-CM. Female prevalence was greater in T60A-hATTR-CM (29.6%) and V122I-hATTR-CM (27.8%) compared to wtATTR-CM (6%). At presentation, females were 3.3 years older than males (wtATTR-CM: 81.9 vs. 77.8 years; T60A-hATTR-CM: 68.7 vs. 65.1 years; V122I-hATTR-CM: 77.1 vs. 74.9 years). Body size significantly influenced measures of disease severity; when indexed, overall structural and functional phenotype was similar between sexes, the few significant differences suggested a mildly worse phenotype in females. No significant differences were observed in both disease progression on serial echocardiography and mortality across the overall population (p = 0.459) and when divided by genotype (wtATTR-CM: p = 0.730; T60A-hATTR-CM: p = 0.161; V122I-hATTR-CM: p = 0.056). Conclusion: this study of a well-characterized large cohort of ATTR-CM patients did not demonstrate overall differences between sexes in either clinical phenotype, when indexed, or with respect to disease progression and prognosis. Non-indexed wall thickness measurements may have contributed to both under-representation and delays in diagnosis for affected females and highlights the potential role of utilizing indexed echocardiographic parameters for a more accurate assessment of patients at diagnosis and for disease prognostication.

Background and Aims The aims of this study were to assess prescription patterns, dosages, discontinuation rates and association with prognosis of conventional heart failure (HF) medications in patients with transthyretin cardiac amyloidosis (ATTR-CA). Methods A retrospective analysis of all consecutive patients diagnosed with ATTR-CA at the National Amyloidosis Centre between 2000-2022 identified 2371 patients with ATTR-CA. Results Prescription of HF medications was greater among patients with a more severe cardiac phenotype, comprising beta-blockers in 55.4%, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin-II receptor blockers (ARB) in 57.4%, and mineralocorticoid receptor antagonists (MRAs) in 39.0% of cases. During a median follow-up of 27.8 months (IQR 10.6-51.3), 21.7% had beta-blockers discontinued, and 32.9% had ACEi/ARB discontinued. In contrast, only 7.5% had MRAs discontinued. Propensity score-matched analysis demonstrated that treatment with MRAs was independently associated with a reduced risk of mortality in the overall population (HR 0.77 [95% CI 0.66-0.89], P40% (HR 0.75 [95% CI 0.63-0.90], P=0.002); and treatment with low-dose beta-blockers was independently associated with a reduced risk of mortality in a pre-specified subgroup of patients with a LVEF ≤40% (HR 0.61 [95% CI 0.45-0.83], P=0.002). No convincing differences were found for treatment with ACEi/ARBs. Conclusions Conventional HF medications are currently not widely prescribed in ATTR-CA, and those that received medication had more severe cardiac disease. Beta-blockers and ACEi/ARBs were often discontinued, but low-dose beta-blockers were associated with reduced risk of mortality in patients with a LVEF ≤40%. In contrast, MRAs were rarely discontinued and were associated with reduced risk of mortality in the overall population; but these findings require confirmation in prospective randomized controlled trials.

Echocardiography has been included as a first-line tool in several international guidelines for the management of patients with various cardiac diseases. Beyond diagnosis, echocardiographic examination helps in characterizing the severity of the condition since the very first stages. In particular, the application of second-level techniques, speckle tracking echocardiography in particular, can also reveal a subclinical dysfunction, while the standard parameters are in the normality range. The present review describes the potentialities of advanced echocardiography in different settings, including arterial hypertension, atrial fibrillation, diastolic dysfunction, and oncological patients, thus opening up potential starting points for its application as a clinical routine changer.

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: The prognostic role of moderate hyperkalemia in reduced ejection fraction (HFrEF) patients is still controversial. Despite this, it affects the use of renin–angiotensin–aldosterone system inhibitors (RAASi) with therapy down-titration or discontinuation. Objectives: Aim of the study was to assess the prognostic impact of moderate hyperkalemia in chronic HFrEF optimally treated patients. Methods and results: We retrospectively analyzed MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) database, with median follow-up of 4.2 [IQR 1.9–7.5] years. Data on K+ levels were available in 7087 cases. Patients with K+ plasma level ≥ 5.6 mEq/L and < 4 mEq/L were excluded. Remaining patients were categorized into normal >4 and < 5 mEq/L (n = 4826, 68%) and moderately high ≥5.0 and ≤ 5.5 mEq/L (n = 496, 7%) K+. Then patients were matched by propensity score in 484 couplets of patients. MECKI score value was 7% [IQR 3.1–14.1%] and 7.3% [IQR 3.4–15%] (p = 0.678) in patients with normal and moderately high K+ values while cardiovascular mortality events at two years follow-up were 41 (4.2%) and 33 (3.4%) (p = 0.333) in each group respectively. Conclusions: Moderate hyperkalemia does not influence patients' outcome in a large cohort of ambulatory HFrEF patients.

Background: Diagnostic and therapeutic advances have led to much greater awareness of transthyretin cardiac amyloidosis (ATTR-CA). We aimed to characterize changes in the clinical phenotype of patients diagnosed with ATTR-CA over the past 20 years. Methods: This is a retrospective observational cohort study of all patients referred to the National Amyloidosis Centre (2002–2021) in whom ATTR-CA was a differential diagnosis. Results: We identified 2995 patients referred with suspected ATTR-CA, of whom 1967 had a diagnosis of ATTR-CA confirmed. Analysis by 5-year periods revealed an incremental increase in referrals, with higher proportions of patients having been referred after bone scintigraphy and cardiac magnetic resonance imaging (2% versus 34% versus 51% versus 55%, chi-square P P P P P =0.01) and higher left ventricular ejection fraction (46.0%±8.9% versus 46.8%±11.0% versus 47.8%±11.0% versus 49.5%±11.1%, P P P P Conclusions: There has been a substantial increase in ATTR-CA diagnoses, with more patients being referred after local advanced cardiac imaging. Patients are now more often diagnosed at an earlier stage of the disease, with substantially lower mortality. These changes may have important implications for initiation and outcome of therapy and urgently need to be factored into clinical trial design.

Aims: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly diagnosed disease. Echocardiography is widely utilized, but studies to confirm the value of echocardiography for tracking changes over time are not available. We sought to describe (i) changes in multiple echocardiographic parameters; (ii) differences in rate of progression of three predominant genotypes; and (iii) the ability of changes in echocardiographic parameters to predict prognosis. Methods and results: We prospectively studied 877 ATTR-CM patients attending our centre between 2000 and 2020. Serial echocardiography findings at baseline, 12 months and 24 months were compared with survival. Overall, 565 patients had wild-type ATTR-CM and 312 hereditary ATTR-CM (201 with V122I; 90 with T60A). There was progressive worsening of structural and functional parameters over time, patients with V122I ATTR-CM showing more rapid worsening of left and right ventricular structural and functional parameters compared to both wild-type and T60A ATTR-CM. Among a wide range of echocardiographic analyses, including deformation-based parameters, only worsening in the degree of mitral (MR) and tricuspid regurgitation (TR) at 12- and 24-month assessments was associated with worse prognosis (change at 12 months: MR, hazard ratio 1.43 [95% confidence interval 1.14–1.80], p = 0.002; TR, hazard ratio 1.38 [95% confidence interval 1.10–1.75], p = 0.006). Worsening in MR remained independently associated with poor prognosis after adjusting for known predictors. Conclusion: In ATTR-CM, echocardiographic parameters progressively worsen over time. Patients with V122I ATTR-CM demonstrate the most rapid deterioration. Worsening of MR and TR were the only parameters associated with mortality, MR remaining independent after adjusting for known predictors.

Coronary flow reserve is the capacity of the coronary circulation to augment the blood flow in response an increase in myocardial metabolic demands and has a powerful prognostic significance in different clinical situations. It might assess with invasive and noninvasive technique. Transthoracic echocardiography Doppler is an emerging diagnostic technique, noninvasive, highly feasible, safe for patient and physician, without radiation, and able to detect macrovascular and microvascular anomalies in the coronary circulation. This review aims to describe the benefit and limits of echocardiographic assessment of coronary flow reserve.

Prognostic stratification of cardiomyopathies represents a cornerstone for the appropriate management of patients and is focused mainly on arrhythmic events and heart failure. Cardiopulmonary exercise testing provides additional prognostic information, particularly in the setting of heart failure. Cardiopulmonary exercise testing data, integrated in scores such as the Metabolism Exercise Cardiac Kidney Index score have been shown to improve the risk stratification of these patients. Cardiopulmonary exercise testing has been analysed as a potential supplier of prognostic parameters in the context of hypertrophic cardiomyopathy, for which it has been shown that a reduced oxygen consumption peak, an increased ventilation/carbon dioxide production slope and chronotropic incompetence correlate with a worse prognosis. To a lesser extent, in dilated cardiomyopathy, it has been shown that the percentage of oxygen consumption peak, not the pure value, and the ventilation/carbon dioxide production slope are associated with a greater cardiovascular risk. Few data are available about other cardiomyopathies (arrhythmogenic and restrictive). Cardiomyopathy patients should be early and routinely referred to heart failure advanced centres in order to perform a comprehensive risk stratification which should include a cardiopulmonary exercise test, with variables and cut-offs shown to improve their risk stratification.

Cor pulmonale is the condition in which the right ventricle undergoes morphological and/or functional changes due to diseases that affect the lungs, the pulmonary circulation, or the breathing process. Depending on the speed of onset of the pathological condition and subsequent effects on the right ventricle, it is possible to distinguish the acute cor pulmonale from the chronic type of disease. Echocardiography plays a central role in the diagnostic and therapeutic work-up of these patients, because of its non-invasive nature and wide accessibility, providing its greatest usefulness in the acute setting. It also represents a valuable tool for tracking right ventricular function in patients with cor pulmonale, assessing its stability, deterioration, or improvement during follow-up. In fact, not only it provides parameters with prognostic value, but also it can be used to assess the efficacy of treatment. This review attempts to provide the current standards of an echocardiographic evaluation in both acute and chronic cor pulmonale, focusing also on the findings present in the most common pathologies causing this condition.

This is an analysis involving 134 heart failure patients with reduced ejection fraction versus 80 controls investigated during functional evaluation with gas exchange and hemodynamic, addressing the severe mitral regurgitation phenotype and testing the hypothesis that the backward cardiac output redistribution to the lung during exercise impairs delivery and overexpresses peripheral extraction. This information is new and has important implications in the management of heart failure.

AIMS In heart failure (HF), the haemodynamic response to exercise in relation to left atrial (LA) dynamics is unexplored. We sought to define whether abnormal LA dynamics during exercise may play a role in cardiac output (CO) limitation and tested its ability to predict outcome. METHODS AND RESULTS A total of 195 HF patients with reduced (n = 105), mid-range (n = 48), and preserved (n = 42) left ventricular ejection fraction (LVEF) and 46 non-cardiac dyspnoea (NCD) subjects underwent cardiopulmonary imaging with assessment of LA strain and strain rate (sra). HF patients, irrespective of LVEF, exhibited a significantly impaired LA strain and LA sra at rest, during exercise and recovery compared to NCD subjects with a blunted response in CO and right ventricular to pulmonary circulation coupling. LA strain and LA sra during exertion were significantly correlated with peak stroke volume index, peak CO and peak cardiac power output (R = 0.33, 0.48, 0.50 and R = 0.36, 0.51, 0.52 for LA strain and LA sra, respectively; all P 2, peak LVEF and peak heart rate, a higher LA strain (1% increase) during exercise was associated with a higher peak stroke volume index (mL/m2 ), CO (L/min) and cardiac power output (mmHg L/min) at multivariable analyses (β-coefficients ± standard error = 0.23 ± 0.07, 0.046 ± 0.014 and 0.012 ± 0.004, respectively; P

Objectives The aim of this study was to identify the pattern of exercise left atrial (LA) dynamics, its gas exchange correlates, and prognosis in mitral regurgitation (MR) of primary and secondary origin. Background The adaptive response and clinical significance of LA function during exercise in MR is undefined. Methods A total of 196 patients with MR (81 with primary MR, 115 with secondary MR) and 54 control subjects underwent exercise stress echocardiography and cardiopulmonary exercise testing with LA function assessment. Patients with MR were divided into 4 groups according to etiology and severity using a cutoff of 3+. Results LA dynamics was studied using speckle-tracking echocardiography. Compared with control subjects, patients with MR had a lower LA strain and strain rate at rest. Exercise LA strain and LA strain rate progressively worsened from primary MR 3+ (25.5; IQR: 23.4 to 29.0); and those with secondary MR Conclusions In MR of any origin, exercise LA reservoir and pump function are impaired. For similar MR extent, secondary MR exhibits worse atrial function, resulting in the lowest exercise performance, limited cardiac output increase, impaired right ventricular–to–pulmonary circulation coupling, and the highest event rate.

Background: In clinical practice, anaerobic threshold (AT) is used to guide training and rehabilitation programs, to define risk of major thoracic or abdominal surgery, and to assess prognosis in heart failure (HF). AT of oxygen uptake (V.O2; V.O2AT) has been reported as an absolute value (V.O2ATabs), as a percentage of predicted peak V.O2 (V.O2AT%peak_pred), or as a percentage of observed peak V.O2 (V.O2AT%peak_obs). A direct comparison of the prognostic power among these different ways to report AT is missing. Research question: What is the prognostic power of these different ways to report AT? Study design and methods: In this observational cohort study, we screened data of 7,746 patients with HF with a history of reduced ejection fraction (< 40%) recruited between 1998 and 2020 and enrolled in the Metabolic Exercise Combined With Cardiac and Kidney Indexes register. All patients underwent a maximum cardiopulmonary exercise test, executed using a ramp protocol on an electronically braked cycle ergometer. Results: This study considered 6,157 patients with HF with identified AT. Follow-up was median, 4.2 years (25th-75th percentiles, 1.9-5.0 years). Both V.O2ATabs (mean ± SD, 823 ± 305 mL/min) and V.O2AT%peak_pred (mean ± SD, 39.6 ± 13.9%), but not V.O2AT%peak_obs (mean ± SD, 69.2 ± 17.7%), well stratified the population regarding prognosis (composite end point: cardiovascular death, urgent heart transplant, or left ventricular assist device). Comparing area under the receiver operating characteristic curve (AUC) values, V.O2ATabs (0.680) and V.O2AT%peak_pred (0.688) performed similarly, whereas V.O2AT%peak_obs (0.538) was significantly weaker (P < .001). Moreover, the V.O2AT%peak_pred AUC value was the only one performing as well as the AUC based on peak V.O2 (0.710), with an even a higher AUC (0.637 vs 0.618, respectively) in the group with severe HF (peak V.O2 < 12 mL/min/kg). Finally, the combination of V.O2AT%peak_pred with peak V.O2 and V. per CO2 production shows the highest prognostic power. Interpretation: In HF, V.O2AT%peak_pred is the best way to report V.O2 at AT in relationship to prognosis, with a prognostic power comparable to that of peak V.O2 and, remarkably, in patients with severe HF.

Thanks to the advances in medical therapy and assist devices, the management of patients hospitalized in cardiac intensive care unit (CICU) is becoming increasingly challenging. In fact, Patients in the cardiac intensive care unit are frequently characterized by dynamic and variable diseases, which may evolve into several clinical phenotypes based on underlying etiology and its complexity. Therefore, the use of noninvasive tools in order to provide a personalized approach to these patients, according to their phenotype, may help to optimize the therapeutic strategies towards the underlying etiology. Echocardiography is the most reliable and feasible bedside method to assess cardiac function repeatedly, assisting clinicians not only in characterizing hemodynamic disorders, but also in helping to guide interventions and monitor response to therapies. Beyond basic echocardiographic parameters, its application has been expanded with the introduction of new tools such as lung ultrasound (LUS), the Venous Excess UltraSound (VexUS) grading system, and the assessment of pulmonary hypertension, which is fundamental to guide oxygen therapy. The aim of this review is to provide an overview on the current knowledge about the pathophysiology and echocardiographic evaluation of perfusion and congestion in patients in CICU, and to provide practical indications for the use of echocardiography across clinical phenotypes and new applications in CICU.

Objectives The aim of this study was to characterize left atrial (LA) pathology in explanted hearts with transthyretin amyloid cardiomyopathy (ATTR-CM); LA mechanics using echocardiographic speckle-tracking in a large cohort of patients with ATTR-CM; and to study the association with mortality. Background The clinical significance of LA involvement in ATTR-CM is of great clinical interest. Methods Congo red staining and immunohistochemistry was performed to assess the presence, type, and extent of amyloid and associated changes in 5 explanted ATTR-CM atria. Echo speckle tracking was used to assess LA reservoir, conduit, contractile function, and stiffness in 906 patients with ATTR-CM (551 wild-type (wt)-ATTR-CM; 93 T60A-ATTR-CM; 241 V122I-ATTR-CM; 21 other). Results There was extensive ATTR amyloid infiltration in the 5 atria, with loss of normal architecture, vessels remodeling, capillary disruption, and subendocardial fibrosis. Echo speckle tracking in 906 patients with ATTR-CM demonstrated increased atrial stiffness (median [25th-75th quartile] 1.83 [1.15-2.92]) that remained independently associated with prognosis after adjusting for known predictors (lnLA stiff: HR: 1.23; 95% CI: 1.03-1.49; P = 0.029). There was substantial impairment of the 3 phasic functional atrial components (reservoir 8.86% [5.94%-12.97%]; conduit 6.5% [4.53%-9.28%]; contraction function 4.0% [2.29%-6.56%]). Atrial contraction was absent in 22.1% of patients whose electrocardiograms showed sinus rhythm (SR) “atrial electromechanical dissociation” (AEMD). AEMD was associated with poorer prognosis compared with patients with SR and effective mechanical contraction (P = 0.0018). AEMD conferred a similar prognosis to patients in atrial fibrillation. Conclusions The phenotype of ATTR-CM includes significant infiltration of the atrial walls, with progressive loss of atrial function and increased stiffness, which is a strong independent predictor of mortality. AEMD emerged as a distinctive phenotype identifying patients in SR with poor prognosis., Central Illustration

Cardiopulmonary exercise testing is a prognostic tool in heart failure with reduced left ventricular ejection fraction (HFrEF). Prognosticating algorithms have been proposed, but none has been validated. In 2017, a predictive algorithm, based on peak oxygen consumption (VO2), ventilatory response to exercise (ventilation [VE] carbon dioxide production [VCO2], the VE/VCO2 slope), exertional oscillatory ventilation (EOV), and peak respiratory exchange ratio, was recommended, according treatment with β blockers: patients with HFrEF registered in the metabolic exercise test data combined with cardiac and kidney indexes (MECKIs) database were used to validated this algorithm. According to the inclusion/exclusion criteria, 4,683 MECKI patients with HFrEF were enrolled. At 3years follow-up, the end point was cardiovascular death and urgent heart transplantation (cardiovascular events [CV]). CV events occurred in 25% in patients without β blockers, whereas those with β-blockers had 11% (p 10

Introduction: The hemodynamic impact of left atrial (LA) intrinsic properties in heart failure (HF) in relation to heart rate (HR) response to exercise has not received attention. Hypothesis: We aimed at investigating the link between LA stiffness and function vs HR reserve (rest to peak exercise) in patients with HF. Methods: A total of 191 patients with HF: 157 β blockers user (LVEF 38 ± 12%, HR reserve 42 ± 18 beats/min) and 34 Non-β blockers user (LVEF 45 ± 19%, HR reserve 36 ± 19 beats/min) underwent cardiopulmonary exercise testing combined with exercise Echo with assessment of LA strain. LA stiffness (median 0.84, IQR 0.44 to 1.89) was assessed using mitral E/E’ /LA strain ratio at rest. Results: HR reserve was positively associated with LA-strain both at rest (20 ± 11%, R = 0.29) and during exercise (20 ± 11%, R = 0.19), LA-strain rate [absolute value] both at rest (1.7 ± 1.0 /s, R = 0.27) and during exercise (1.6 ± 1.2 /s, R = 0.26) and peak VO 2 (14 ± 4 mL/kg/min, R = 0.62), and negatively associated with LA volume index (44 ± 23 ml/m 2 , R = -0.29), log-transformed LA stiffness (R = -0.35), mitral regurgitation (from 0 to 4+) both at rest (R = -0.28:) and peak exercise (R = -0.25) and VE/VCO 2 slope (32 ± 8, R = -0.32)(figure) (P Conclusions: In HF patients, age and LA stiffness play a key role in HR response to exercise irrespective of β blockers prescription. These data may offer additional insights in the concepts of exercise limitation in HF.

Introduction: The relationship between TAPSE vs heart rate (HR) during physical exercise may well represent the force-frequency relationship of the right ventricular (RV) whose impact on exercise performance and hemodynamics may translate in interesting insight. Aims: to phenotype heart failure (HF) patients based on the response in TAPSE vs HR. Methods: A total of 164 patients with HF and 32 healthy subjects with normal RV to pulmonary circulation (Pc) coupling, left atrium (LA) size and reservoir function (LA volume index 2 and LA-strain >23%) underwent cardiopulmonary exercise testing combined with exercise Echo. TAPSE/HR slope was assessed using (peak TAPSE - rest TAPSE)/(peak HR - rest HR) ratio. According to the 95% confidence interval of TAPSE/HR slope (0.03 - 0.13, median 0.06) in healthy subjects, HF patients were divided into 2 groups: responders (TAPSE/HR ≥0.03, n=108) and non-responders ( Results: There was no significant difference in age (65±12 vs 68±13 years), sex (70 vs 63% male), peak VO 2 (14±4 vs 13±4 ml/kg/min), and VE/VCO 2 slope (32±8 vs 33±10) between responder and non-responder group. However, responders exhibited a higher LA-strain at rest (21±12 vs 17±10%) and exercise (21±12 vs 17±10%), and a lower LA volume index (43±21 vs 52±27 ml/m 2 ) and mitral E/e’ (18±10 vs 22±11) than non-responders, respectively (P Conclusions: The RV force-frequency relationship may be impaired in HF. Especially in non-responders the lack of adaptive RV performance combines with worse RV to Pc coupling and atrial dysfunction. These data may offer additional insights in the concepts of exercise limitation in HF.

Background Left atrial (LA) dynamics play a key role in the hemodynamics assessment of heart failure (HF). LA strain analysis by speckle tracking echocardiography (STE) has recently been introduced in clinical practice. In acute decompensated heart failure (ADHF), LA functional deterioration leads to worsening of pulmonary capillary hypertension and congestion, ultimately impacting prognosis. However, how LA size and function behaves in ADHF according to the different HF phenotypes has never been studied. Purpose To evaluate the diverse morphology and dynamics of the LA, along with a thorough congestion analysis, in ADHF patients with HFpEF, HFmrEF and HFrEF. Methods Eighty-five ADHF patients (mean age 75.6±10.4 years, 59% males) were prospectively enrolled within 24–48 hours from admission to the emergency department. In the acute phase all patients underwent a complete transthoracic echocardiography (TTE) and lung ultrasonography (LUS) associated with blood sample and a thorough clinical examination. LA mechanics was assessed with STE, through the evaluation of global peak atrial longitudinal strain (GPALS). Results Out of 85 patients, 51% were classified as HFrEF, 20% as HFmrEF and 29% as HFpEF. At admission, all patients exhibited a comparable degree of congestion, as testified by increased IVC max. diameter (HFpEF 19±7 mm vs HFrEF 20±6.3 mm vs HFmrEF 17±5.3 mm, p=0.167), incremented PASP (HFpEF 39.2±13.5 mmHg vs HFrEF 42±12 mmHg vs HFmrEF 35.3±10.1 mmHg, p=0.15) and a rising number of B-lines on LUS (HFpEF 20±12.8 vs HFrEF 24±17 vs HFmrEF 21±19, p=0.62). Increased NT-proBNP values in the cohort were also noted, with HFrEF exhibiting the highest levels (HFrEF 11747±1069 ng/l vs HFmrEF 6905±811 ng/l vs HFpEF 3918±374 ng/l; p Conclusions ADHF patients exhibit an heterogeneous response in terms of LA size and function according to LVEF categorization. The definition of subjects expressing the worst coupling between LA size and function appears of relevance in order to facilitate risk stratification and identify patients at higher risk of early re-hospitalization. Funding Acknowledgement Type of funding sources: None.

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 Heart failure (HF) patients are categorized according to left ventricular ejection fraction (LVEF), being such index both easily feasible and prognostic. However, the risk stratification of patients hospitalized for acute decompensated heart failure (ADHF) according to the absolute value of LVEF at presentation is unexplored and its prognostic significance has not been tested against stroke volume indexed (SVi). Purpose To examine the prognostic impact of SVi versus LVEF in patients hospitalized for ADHF (wet and warm phenotype). Methods Eighty-five ADHF patients (mean age 75.6±10.4 years, 59% males) were prospectively enrolled within 24–48 hours from admission to the emergency department. In the acute phase all patients underwent a complete transthoracic echocardiography (TTE) and lung ultrasonography (LUS) associated with blood sample and a thorough clinical examination. Patients were then stratified into two groups according to the presence or the absence of a preserved SVi at admission (SVi ≥35 ml/m2). Results During a median follow-up (FU) time of 12 months (IQR months 8–15 months) we observed a CV event rate of 28.2%. During the FU period 14 patients (16.5%) were re-hospitalized for ADHF, 7 patients died for CV reason (8.2%), 1 patient underwent mitral valve replacement for severe chronic mitral regurgitation, 1 patient was re-hospitalized for cardiac resynchronization therapy and 1 subject was re-hospitalized for acute coronary syndrome. Interestingly, patients that had a preserved TTE-derived SVi at admission (SVi ≥35 ml/m2) exhibited a significantly higher survival, when compared to subjects that showed an impairment of cardiac output at rest (SVi Conclusions Although the categorization of LVEF in CHF patients bears a pivotal classificatory and prognostic role, its assessment in ADHF, may lack of prognostic value especially when compared to SVi which represents a better parameter to define high-risk subjects who benefit from closer monitoring. Funding Acknowledgement Type of funding sources: None.

Background The hemodynamic impact of left atrial (LA) dynamics in aortic stenosis (AS) in relation to cardiopulmonary response to exercise has never been studied. We aimed at investigating the link between LA function vs hemodynamics and prognosis in asymptomatic severe AS patients. Methods A total of 106 patients: 76 asymptomatic severe AS patients (aortic valve area (AVA) Results Normal-flow low-gradient AS (NFLG: PV 35ml/m2, LVEF ≥50%, N=23), High-gradient AS (HG: PV ≥4 m/s or MPG ≥40 mmHg, LVEF ≥50%, N=23), Paradoxical low-flow low-gradient AS (PLFLG: PV Conclusions In asymptomatic severe AS, the study of LA functional adaptation to exercise plays a key role in the hemodynamic unfavorable cascade signaling major adaptive differences in dynamics during physical challenge. Overall, LA dynamics provides prognostic information also in AS patients. 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

Background Left ventricular (LV) dilatation plays a key role on functional mitral regurgitation (MR) in patients with heart failure (HF) and exercise MR causes an additional LV remodeling. This study sought to investigate the different phenotypes and prognostic impact of LV end-diastolic volume (EDV) and MR during exercise in HF patients of any left ventricular ejection fraction (LVEF) categorization. Methods 201 HF patients with reduced (n=119), mildly-reduced (n=46), and preserved (n=36) EF underwent exercise with gas exchange analysis combined with echocardiography for assessment of MR and were divided by 3 groups according to EDV index tertiles (T1 95.6 ml/m2). Results There was no significant difference in age (67±12 years) and peak oxygen consumption (VO2: 13.1±3.7 ml/kg/min) among the 3 groups but VE/VCO2 slope was higher in T3 group (T1 31±7, T2 31±5, T3 37±11, P2+ was 1.8 (P=0.049) at rest and 1.9 (P=0.026) at exercise. The age, gender, peak VO2, VE/VCO2 slope, and exercise MR >2+ adjusted hazard ratio of EDV index 10 ml/m2 increase was 1.1 (P=0.041) and the ratio in patients with EDV index >95.6 ml/m2, derived by ROC curve (AUC=0.69, P Conclusions Functional MR with LV dilation combines with the worse exercise gas exchange phenotype. Given also the predictive role of a EDV index cutoff of 95.6 ml/m2 attention for chamber geometry during exercise might become an indicator of mitral valve reparation. Funding Acknowledgement Type of funding sources: None.