INTRODUCTION:Approximately two-thirds of patients suffering from hypertrophic cardiomyopathy present with an obstructive (HOCM) physiology. For years, medical therapy has been limited to beta blockers, verapamil and/or disopyramide. Recently, a novel class of drugs, the allosteric inhibitors of the cardiac-specific myosin head adenosine triphosphatase (ATPase), have been demonstrated to be effective in relieving the dynamic obstruction and related clinical condition. In July 2024 the Cardiomyopathies and Pericardial Diseases WG of the Italian Society of Cardiology started with a nationwide multicentre registry aimed at investigating the pathophysiology of dynamic obstruction in real-world patients with HOCM. Based on the medical records, this brief report deals with the proportion of patients who were eligible for Mavacamten based on the Explorer-HCM entry criteria, and then admitted for compassionate use by the end of 2024. METHODS AND RESULTS:The Hypertrophic Obstructive Physiology Study (HOPS) was designed as a registry on consecutive adult patients admitted to 19 tertiary Cardiac Centres in Italy until June 2024. A total of 424 patients, 53% males, aged 64 ± 13 years, were included. We retrospectively recognized 200 Mavacamten-eligible patients (47.2%) on 5 Explorer-HCM requirements. Forty out of this latter group, along with 15 more patients on 4 criteria, were admitted to the compassionate use programme ( n  = 55, 13% of the whole population). Forty-three showed subaortic obstruction and 12 a mid-ventricular variant. Ethical committee approval items varied among centres and regions. DISCUSSION:This study confirmed our recent demonstration that approximately half of real-world HOCM patients are suitable for Mavacamten therapy based on the full Explorer-HCM trial entry criteria. Due to the current limitation of compassionate use programmes in Italy, only one in four patients was admitted for treatment.

Cardiac amyloidosis (CA) is a progressive infiltrative cardiomyopathy commonly linked to heart failure (HF) symptoms. Ventricular arrhythmias (VA) may occur in a small subset of patients, typically in advanced stages when amyloid deposits compromise myocardial and conduction system integrity. Managing VA in asymptomatic patients with CA remains complex and debated, particularly regarding beta–blockers due to potential adverse effects. A 65–year–old male, an experienced runner (10 km/day), presented for a primary prevention cardiological assessment. His history included dyslipidemia and smoking. He denied symptoms such as dyspnea, angina, syncope or palpitations. An electrocardiogram (ECG) showed sinus bradycardia, first–degree AV block, inferoseptal QS waves and altered lateral leads repolarization. Recent transthoracic echocardiography (TTE) suggested hypertrophic cardiomyopathy. 24–hour ECG Holter monitoring identified frequent asymptomatic non–sustained ventricular tachycardia (NSVT), prompting Emergency Department evaluation. Blood tests showed normal complete blood count, electrolytes, and thyroid function, with Troponin T at 55 ng/L, CK–MB 7.5 ng/mL, BNP 219 pg/mL, and NT–proBNP 3776 pg/mL. During hospitalization in our Cardiology department, the patient remained asymptomatic. Complete TTE showed severe biventricular wall thickening with a granular sparkling appearance, severe impairment of global left ventricular (LV) longitudinal myocardial deformation (GLS = –7.8%) with “apical sparing” pattern, a mildly impaired LV ejection fraction (EF), LV diastolic dysfunction, and thickening of interatrial septum, raising suspicion for cardiac amyloidosis (Figure 1-2). Tests for AL amyloidosis were negative, including serum/urine immunofixation and free light chain assay (kappa/lambda). Bone scintigraphy (99mTc–HMDP) revealed a Perugini score of 3. Cardiac magnetic resonance imaging confirmed severe increase in LV wall thickness with global hypokinesia (LVEF of 41%) and extensive biventricular late gadolinium enhancement, sparing the apical segments (Figure 3). Coronary angiography found no significant lesions. Telemetry documented recurrent asymptomatic NSVT episodes, leading to initiation of bisoprolol, titrated to 2.5 mg twice daily. The patient was discharged on this well–tolerated regimen, which reduced the arrhythmic burden. HF therapy was initiated. Genetic testing for transthyretin CA and extended genetic analysis for cardiomyopathies are ongoing.Figure 1 Figure 2 Figure 3

Background RV reserve has been linked to exercise capacity and prognosis in cardiopulmonary diseases. However, evidence in this setting is limited, due to the complex shape and load dependency of the RV. We sought to study right ventricular (RV) adaptation to exercise by simultaneous three-dimensional echocardiography (3DE) and right heart catheterization (RHC). Methods Patients with heart failure with preserved ejection fraction (HFpEF) or pulmonary vascular disease (PVD) underwent simultaneous supine rest/exercise RHC-3DE. They were subdivided based on RV ejection fraction (EF) changes: 1)exhausted RV reserve, RVEF-; 2)preserved RV reserve, RVEF+. Results Sixty percent of patients were RVEF-. Distribution of HFpEF/PVD, as well as RV volumes and RVEF at rest were similar in the two groups. Hemodynamic metrics of RV afterload, as well as their exercise-induced changes, were similar in the two groups. During exercise, RV end-diastolic volume increased more in RVEF- than in RVEF+ (29±29 vs 7±25 mL,p<0.05). RV end-systolic volume increased by 21[12;31]mL in RVEF- and decreased by 8[-15;1]mL in RVEF+ (p<0.001). RV-pulmonary artery coupling was lower in RVEF- at peak exercise(p<0.05). Peak RVEF was associated with left ventricular preload (R2=0.14,p=0.011). Cardiac output increased less in RVEF- than in RVEF+ (+2.3±2.0 vs +4.0±2.4 L/min,p<0.05). Peak RVEF was associated with oxygen consumption(p<0.01). Conclusions Exhausted RV reserve, as evaluated by 3DE, was frequent in HFpEF and PVD, was relatively independent from classical afterload parameters, was associated with RV-pulmonary artery decoupling, RV dilation, enhanced ventricular interdependence, and cardiac limitation to exercise. Intrinsic RV dysfunction may contribute to exhausted RV reserve.

Aims To compare the effects of LV volume overload due to chronic organic MR or AR on RV shape and function. Methods and results We studied 63 patients with moderate-severe or severe primary MR and 36 patients with moderate or severe AR. 3D echocardiography of LV and RV was performed to measure volumes and EF. RV fractional area change (FAC) was calculated, and RV shape was assessed by calculating the RV eccentricity index.LV EDVi was significantly larger in the patients with AR than in those with MR. RV EF and RV FAC were lower in pts with AR than in those with MR. RV EI was significantly higher in the AR group. In both groups, LV EDVi showed positive correlations with RV EI ( r= 0.693 for AR and r=0.399 for MR) and negative correlations (RV EF :r= -0.545 for AR and r=- 0.383 for MR ; RV FAC: r=-0.816 for AR and r=-0.647 for MR, ). LV sphericity index showed negative correlations (RVFAC: r= -0.512 and r=-0.608 f ;RV EF:r=-0.408 and r=-0.469 respectively ) and positive correlation with the RV EI (r= 0.39 and r=0.511 respectively) .LV EDVi and LV sphericity index were found to be the only independent predictors of RV eccentricity index, EF, and FAC. Conclusions RV remodeling in chronic LV overload due to MR or AR occurs independently on PASP values. LV size and shape are the only independent predictors of RV geometry and function. Accordingly, chronic AR has a greater impact on RV than MR

Aims The European Association of Cardiovascular Imaging (EACVI) Scientific Initiatives Committee performed a global survey on radiation exposure in interventional echocardiography. The survey aimed to collect data on local practices for radioprotection in interventional echocardiography and to assess the awareness of echocardiography operators about radiation-related risks.Methods and results A total of 258 interventional echocardiographers from 52 different countries (48% European) responded to the survey. One hundred twenty-two (47%) participants were women. Two-thirds (76%) of interventional echocardiographers worked in tertiary care/university hospitals. Interventional echocardiography was the main clinical activity for 34% of the survey participants. The median time spent in the cath-lab for the echocardiographic monitoring of structural heart procedures was 10 (5-20) hours/month. Despite this, only 28% of interventional echocardiographers received periodic training and certification in radioprotection and 72% of them did not know their annual radiation dose. The main adopted personal protection devices were lead aprons and thyroid collars (95% and 92% of use, respectively). Dedicated architectural protective shielding was not available for 33% of interventional echocardiographers. Nearly two-thirds of responders thought that the radiation exposure of interventional echocardiographers was higher than that of interventional cardiologists and 72% claimed for an improvement in the radioprotection measures.Conclusion Radioprotection measures for interventional echocardiographers are widely variable across centres. Radioprotection devices are often underused by interventional echocardiographers, portending an increased radiation-related risk. International scientific societies working in the field should collaborate to endorse radioprotection training, promote reliable radiation dose assessment, and support the adoption of radioprotection shielding dedicated to interventional echocardiographers.

Abstract Background/Introduction Secondary tricuspid regurgitation (STR) can develop from markedly different etiologies. Both progressive dilation and dysfunction of the right atrium (atrial phenotype, ASTR), and adverse right ventricular (RV) remodeling (ventricular phenotype, VSTR) may result in STR. RV function is a major determinant of outcome in patients with STR. However, data about how RV function adapts to ASTR and VSTR are scarce, and the prognostic implications of RV mechanics in ASTR and VSTR remain to be clarified. Purpose Accordingly, we aimed to investigate the RV mechanical patterns in ASTR and VSTR and to examine their prognostic role using three-dimensional (3D) echocardiography. Methods We enrolled 192 patients with STR (60% women) who underwent clinically indicated transthoracic echocardiography in a multicentric prospective observational study. The primary outcome was defined as a composite of heart failure hospitalization or cardiac death. STR etiology was assessed based on the TVARC criteria (ventricular STR n=134, atrial STR n=58). STR severity was categorized using STR effective regurgitant orifice area according to current guidelines. We assessed RV function by measuring the tricuspid annular plane systolic excursion (TAPSE) by M-mode echocardiography and RV ejection fraction (EF) by 3D echocardiography. In addition, we imported the 3D RV meshes into the ReVISION software package (Argus Cognitive, Inc, Lebanon, USA) to quantify the relative contribution of the longitudinal (LEFi), radial (REFi), and anteroposterior motion components (AEFi) to total RV EF. Results ASTR and VSTR patients had comparable TAPSE (17±5 mm vs. 18±5 mm, p=0.10), while RV EF was significantly higher in ASTR (54±7% vs. 47±10% p<0.001). Although LEFi (0.37±0.08 vs. 0.38±0.10, p=0.95) and AEFi (0.45±0.08 vs. 0.44±0.11, p=0.53) were comparable between ASTR and VSTR, REFi was significantly lower in VSTR (0.52±0.09 vs. 0.47±0.12, p<0.01). RF EF was comparable among STR severity grades (mild vs. moderate vs. severe: 50±11 vs. 49±9 vs. 50±10%, respectively, p=0.85). Conversely, LEFi was significantly higher in mild and moderate STR vs severe STR (0.39±0.08 vs. 0.39±0.09 vs. 0.35±0.10, respectively, p=0.04). Using multivariable Cox regression based on variables significant in the univariate analysis, REFi was a significant independent predictor of outcome in the entire cohort (hazard ratio: 0.978 [CI, 0.959-0.999], p= 0.037). Conclusions Using 3D echocardiographic assessment, ASTR and VSTR patients demonstrated significant differences in the RV mechanical pattern, with a lower contribution of the radial contraction in the case of ventricular STR etiology. While RV EF was comparable between STR severity grades, the relative importance of the longitudinal motion significantly differed. Notably, the relative contribution of radial motion to RV function demonstrated independent prognostic value in patients with STR.RV mechanics in STR severity stages

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EFOP-3.6.3-VEKOP-16-2017-00009 project. Background The conventional echocardiographic parameters of the right ventricular (RV) systolic function (e.g., tricuspid annular plane systolic excursion - TAPSE, fractional area change - FAC) only partially portray the complex functional characteristics of the RV; therefore, they may fail to capture the full spectrum of RV dysfunction and associated adverse clinical outcomes. 3D echocardiography-derived RV ejection fraction (RVEF) is a well-validated and reproducible parameter that overcomes these limitations. Purpose We aimed to investigate the discordance between TAPSE, FAC and RVEF in RV systolic function grading and associated outcomes. Methods Two retrospective databases from different centers including consecutive patients with various cardiac diseases who underwent clinically indicated 2D and 3D echocardiography (n=750) were analysed. Patients were followed up for the occurrence of all-cause mortality. RVEF was measured by a single, commercially available 3D software package. Guideline-recommended cut-off values were used to indicate RV systolic dysfunction (TAPSE<17 mm, FAC<35%). RVEF <45% served as the "ground truth" of RV dysfunction. Results Among patients with normal RVEF (n=511), 109 (21%) had reduced TAPSE, 168 (33%) had reduced FAC, and 49 (10%) had both reduced TAPSE and FAC. Among patients with reduced RVEF (n=239), 108 (45%) had normal TAPSE, 57 (24%) had normal FAC, and 38 (16%) had both normal TAPSE and FAC. Correspondingly, sensitivity and specificity for discrimination of RV systolic dysfunction (RVEF<45%) were 66% and 70% for TAPSE, and 71% and 76% for FAC on ROC analysis, respectively (Figure 1). During the median follow-up time of 3.7 years, 112 patients (15%) died. Using univariable Cox regression, TAPSE (HR [95% CI]: 0.911 [0.881–0.942]), FAC (0.940 [0.924–0.957]), and RVEF (0.928 [0.913–0.944]) were all significant predictors of mortality (p<0.001). Interestingly, combination of the functional assessments based on either TAPSE or FAC with RVEF separates four risk groups that differ significantly in terms of all-cause mortality (Kaplan-Meier curves, Figure 2, log-rank p<0.05). Conclusion Guideline-recommended cut-off values of conventional echocardiographic parameters of RV systolic function are only modestly associated with RVEF-based assessment. This phenomenon may hinder the proper risk stratification of patients with RV systolic dysfunction.

Abstract Funding Acknowledgements Type of funding sources: None. Background Right ventricular (RV) function is strongly associated with the prognosis of patients with secondary tricuspid regurgitation (STR). However, the mechanical adaptations (contraction pattern) of the RV to volume overload associated with STR remain to be clarified. Purpose To investigate the changes in RV contraction pattern associated with the increase in severity of STR and to analyse whether the assessment of each RV motion component of RV ejection fraction (RVEF) (longitudinal, radial, and anteroposterior) adds prognostic value in patients with STR. Methods Consecutive patients with STR who underwent clinically indicated transthoracic echocardiography were enrolled in a multi-center prospective observational study. The primary outcome was defined as heart failure hospitalization or cardiac death. 3-dimensional echocardiography studies were performed at baseline and the ReVISION software package (Argus Cognitive, Inc, Lebanon, NH) was used to quantify the contribution of the longitudinal, radial, and anteroposterior motion components to total RVEF (Figure). Results We enrolled 172 patients (43% men, age: 75±15 years), followed for a median of 9 months. The patients were divided in two groups by STR severity (non-severe n=125, severe n=47). The characteristics of patients with massive/torrential STR (n=12) vs. "only" severe STR (n=35) were also assessed. RV end-diastolic volume index (r=0.33, p<0.001) and the longitudinal component of RVEF demonstrated significant correlation with STR severity (r=-0.22, p<0.01), while total RVEF did not (r=0.14; p = NS). The anteroposterior component of RVEF was the only parameter showing relatively strong correlation with left ventricular ejection fraction (r=0.39; p<0.001). RVEF was comparable between non-severe and severe patients (49±10 vs. 49±11%, p = NS). In patients with severe STR, the radial and also anteroposterior component of RVEF were comparable to non-severe STR patients, while the longitudinal component was significantly lower in severe STR (19±6 vs.17±7%, p<0.05; shown on Figure). Notably, in patients with massive/torrential STR, the radial contribution markedly decreased (27±8 vs. 20±9%, p<0.05), with consequently reduced global RVEF (52±9 vs. 41±12%, p<0.01) (Figure). In a multivariable Cox regression, using parameters proved to be significant in the univariable analysis, longitudinal component of total RVEF was a significant and independent predictor of outcome (hazard ratio, 0.947 [CI, 0.903–0.992], P= 0.022). Conclusions Patients with severe STR demonstrate significant morphological and functional RV remodeling with chamber enlargement and maintained RVEF, but a significant decrease in the longitudinal component of RVEF. In patients with massive/torrential STR, the radial mechanism markedly deteriorates, leading to decreased global RVEF. The longitudinal component of RV motion demonstrated independent prognostic value in patients with STR.

Abstract Funding Acknowledgements Type of funding sources: None. Background Current quantitative parameters used to assess the severity of secondary tricuspid regurgitation (STR) do not account for the size of the right ventricle (RV). To address this issue, the concept of proportionality of the severity of the STR to the size of the RV has been recently mutuated from the mitral regurgitation field to improve the prognostic stratification of patients with STR. Purpose We sought to compare the prognostic value of a classification of STR based on the proportionality of the regurgitant volume (Reg Vol) to the RV stroke volume with the guideline-recommended grading scheme of STR severity. Methods Patients with at least mild STR were prospectively enrolled and underwent complete 2D, Doppler and 3D echocardiography with the measurement of RV volumes. To determine STR proportionality status, we evaluated the difference between the measured and the theoretical RegVol of severe STR (the latter was defined as the RV stroke volume needed to have a regurgitant fraction [RF] ≥ 50% according to the actual RV stroke volume). This classification took into account a bias of 8 ml in the computation of Reg Vol, derived from Bland-Altman analysis (picture 1). Accordingly, patients were classified as non severe (NS_STR, measured RegVol< theoretical RegVol), severe proportionate (SP_STR, measured RegVol ≈ theoretical RegVol), and severe disproportionate (SD_STR, measured RegVol > theoretical RegVol) STR (picture 1). The incidence of the combined endpoint of heart failure (HF) hospitalization and death for any cause was used as the primary endpoint. Results We enrolled 333 consecutive patients (mean age 71±14 years, 53.3 % women). After a median follow up of 20 months (10–32), 134 patients (40.2%) reached the combined end point. Patients with SD_STR showed a significantly higher incidence of events (67.9%) in comparison to patients with SP_STR (40.6%, p = 0.005 for difference) and NS_STR (31.3%, p<0.001 for difference) (picture 2). At Cox multivariate analysis, the proportionality of STR (adjusted for age, atrial fibrillation, right atrial volume, RV free-wall longitudinal strain, and RV ejection fraction) independently correlated with the combined endpoint (adjusted hazard ratio: 1.785; 95% confidence interval [CI]: 1.249–2.550; p = 0.002). When tested with the same variables, the conventional STR severity grade lost its independent correlation with combined end point (p = 0.258). Conclusions Disproportionate STR is independently associated with all-cause mortality or heart failure hospitalization, and it improves the risk stratification of patients compared to the guideline-recommended grading scheme of STR severity.

Abstract Funding Acknowledgements Type of funding sources: None. Background. In most laboratories three-dimensional echocardiography (3DE) and longitudinal strain (Lstrain) analysis are not part of the routine studies. Although these modalities have been shown to provide additional clinical information and prognostic value compared to conventional two-dimensional echocardiography (2DE), their acquisition and analysis are perceived as being time-consuming. Recently, new automated tools have been developed to perform accurate, fast and reproducible analyses of heart chambers’ geometry and function. However, their cost-effectiveness when compared to conventional 2DE remains to be demonstrated. Aim. We designed a prospective, multicenter, observational study aimed to compare the time required for the acquisition and analysis of conventional transthoracic 2DE vs advanced echocardiography (AEcho, i.e. 3DE+ Lstrain) for the assessment of cardiac chambers and myocardial mechanics. Methods. According to current guidelines, 196 consecutive patients referred for clinically indicated echocardiography underwent complete 2DE and Doppler echocardiography. In addition, 3DE datasets of the left atrium (LA), left and right ventricle (LV, RV) were acquired using automated 3DE software package (Heart Model). Acquisition time for both 2DE and 3DE images were recorded. Conventional 2DE analyses of LA (biplane volume), LV (biplane volumes and mass) and RV (both linear dimensions, areas, and longitudinal function) were performed following current guidelines, and the time required for acquisition and analysis was recorded. The time spent for AEcho analysis (both 3DE volumetric analysis and Lstrain of LA, LV and RV) was also recorded. Results. Feasibility of AEcho was 86% (169 patients). The additional time for 3D dataset acquisition over conventional 2DE was 38 ± 0.16 sec. Quantitative analysis of the cardiac chambers by 2DE required an average of 5.55 ± 1.51 min vs 4.25 ± 1.23 min using AEcho (p < 0.001). Total time for both 3D dataset acquisition and AEcho assessment was 5.03 ± 1.28 min vs 5.55 ± 1.51 min of 2DE analysis alone (p < 0.001). Globally, AEcho provided a more comprehensive assessment of heart chambers than 2DE (Table). Moreover, the time spent for 3DE dataset acquisition and AEcho analysis on top of standard 2DE acquisition was significantly shorter compared to the 2DE acquisition and analysis (18:50 ± 4.23 vs 19:42 ± 4.24 min, p < 0.001) (Table). Conclusions. Our data showed that the use of new AEcho automated tools are highly feasible resulting in significant time-savings compared to standard 2DE evaluation, while providing significant additional information. Abstract Table

Abstract Background Right heart failure (RHF) represents the final step of distinct diseases, such as pulmonary arterial hypertension (PAH) and pulmonary hypertension (PH) due to heart failure with preserved ejection fraction (HFpEF). RHF may be defined by the inability of the heart to maintain a normal cardiac output (CO) or to do so at the expense of high right atrial pressure (RAP), at rest or during exercise. However, exercise hemodynamic features suggestive of RHF, as well as their determinants, have still not been defined. Aim We sought to i. define the limits of normal of RAP increase during exercise; ii. describe the behavior of RAP during exercise in PAH and in PH-HFpEF, and its relation to right heart afterload and preload. Methods We retrospectively analyzed data from consecutive patients referred for suspicion of PH, who underwent both a resting and exercise right heart catheterization at two centers with identical methodology. We included patients with PH-HFpEF or PAH. Right heart adaptation to exercise was described either using absolute or CO-normalized RAP increase during exercise (RAP/CO slope), this latter representing the inverse of the Frank-Starling reserve. A control cohort of subjects with normal hemodynamics at rest and during exercise served to define abnormal increase in RAP, i.e. values of RAP and RAP/CO slope > mean ± 2 standard deviation of controls. Estimated stressed blood volume (eSBV), as a measure of effective preload, was computed using a commercially-available software. Results 80 patients were included in the analysis, of which 29 were PH-HFpEF, 30 PAH and 21 controls. HFpEF patients were older than PAH patients and with a higher burden of cardiovascular comorbidities (p<0.05). Sex representation, BMI, and NTproBNP values were similar in the two groups. Mean pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR) and total vascular resistance (TPR) were higher in PAH than in PH-HFpEF both at rest and during exercise (p<0.01), in spite of similar CO (Table 1). At rest, eSBV did not differ between HFpEF and PAH, but it was higher in HFpEF at peak exercise. On average, PH-HFpEF had higher resting and peak RAP than PAH, as well as higher RAP/CO slope (Figure 1). The upper limit of normal of exercise RAP and of RAP/CO slope, as determined in control subject, was 12 mmHg and 1.55 mmHg/L/min. A higher rate of HFpEF patients, compared with PAH, had a RAP/CO slope and a peak RAP above normal limits (78% and 91% of PH-HFpEF vs 47% and 44% of PAH, respectively, p<0.001). RAP/CO slope in the whole cohort was associated with eSBV but not with right ventricular afterload measures (PAP, TPR, PVR). Conclusions PH-HFpEF display more frequently a steeper increase of RAP during exercise than PAH patients in spite of similar CO, suggesting a more exhausted Frank-Starling reserve. The steep RAP increase during exercise seems to reflect a dysfunctional preload rather than an afterload-mismatch. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship.

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 Background Right heart failure (RHF) represents the final step of distinct diseases, differently involving the pulmonary circulation, such as pulmonary arterial hypertension (PAH) and pulmonary hypertension (PH) due to heart failure with preserved ejection fraction (HFpEF). Exercise may unmask right heart maladaptation as a sign of RHF, but cut–offs for right atrial pressure (RAP) rise during exercise remain to be defined. We hypothesized that PH–HFpEF may present with worse right heart adaptation to exercise than PAH due to increased chamber stiffness and dysfunctional preload. Aim We sought to describe the behavior of RAP during exercise in PAH and in PH–HFpEF, and the mechanisms underlying right heart maladaptation. Methods We performed a retrospective analysis of data (2007–2021) obtained from patients with either PAH or PH–HFpEF who underwent a right heart catheterization at rest and during exercise. Right heart adaptation to exercise was described using either absolute or cardiac output (CO)–normalized RAP increase during exercise (RAP/CO slope). Patients with non–cardiac dyspnea (NCD) served to define RAP limits of normality. Estimated stressed blood volume (eSBV), as a measure of effective preload, was computed based on hemodynamics using a commercially–available software. Results Ninety–four patients were included (32 PH–HFpEF, 32 PAH and 30 NCD). The upper limit of normal for absolute peak RAP and RAP/CO slope were 12 mmHg and 1.55 mmHg/L/min. Compared with PH–HFpEF, PAH patients showed higher systolic, diastolic and mean pulmonary artery pressure (PAP) as well as higher indices of right ventricular afterload both at rest and during exercise, but lower filling pressures and similar CO (Figure 1).In particular, PH–HFpEF had higher peak RAP and higher RAP/CO slope than PAH (Figure 1,2). Additionally, 78% and 91% of PH–HFpEF, as compared with 47% and 44% of PAH had a RAP/CO slope and a peak RAP above normal, respectively (p < 0.001). PH–HFpEF presented with higher increase in eSBV, and higher peak eSBV values than PAH (p < 0.05), despite similar resting levels. RAP/eSBV slope was upward shifted (at a given effective preload, RAP was higher) while CO/eSBV slope was flatter (at a given effective preload, CO was lower) in PH–HFpEF as compared with PAH (Figure 3). Conclusions PH–HFpEF display worse right heart maladaptation to exercise than PAH, likely due to a combination of increased right heart stiffness and a more exhausted Frank–Starling reserve.

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf MASCOT investigators Background Few studies analyzed left atrial (LA) peak atrial longitudinal strain (PALS) determinants, particularly across heart failure (HF) stages. We aimed to analyze the pathophysiological and clinical PALS correlates in a large international prospective registry. Methods This is a multicenter prospective observational study enrolling 745 patients with HF stages 0-C from July to October 2018. Data included PALS and left ventricular global longitudinal strain (LV-GLS). Exclusion criteria were: valvular prosthesis; atrial fibrillation; cardiac transplantation; poor acoustic window. Results Median global PALS was 17% [24-32]. 29% of patients were in HF-stage 0/A, 35% in stage-B, and 36% in stage-C. Together with age, the echocardiographic determinants of PALS were LA volume and LV-GLS (overall model R²=0.50, p < 0.0001). LV-GLS had the strongest association with PALS at multivariable analysis (beta:-3.60 ± 0.20, p < 0.0001). Among HF-stages (Figure 1), LV-GLS remained the most important PALS predictor (p < 0.0001) whereas age was only associated with PALS in lower HF-stage 0/A or B (R=-0.26 p < 0.0001, R=-0.23 p = 0.0001). LA volume increased its association to PALS moving from stage 0-A (R=-0.11; P = 0.1) to C (R=-0.42; P < 0.0001). PALS was the single most potent echocardiographic parameter in predicting HF stage (AUC for B vs. 0/A 0.81, and AUC vs. 0/A for C 0.76). PALS remained independently associated with HF stages after adjusting for ejection fraction, E/e’ ratio and mitral regurgitation grade (p < 0.0001). Conclusion Although influenced by LV-GLS and LA size across HF-stages, PALS is incrementally and independently associated with clinical status. LA function may reflect a substantial part of the hemodynamic consequences of ventricular dysfunction. Abstract Figure 1

Abstract Echocardiography is the gatekeeper of the diagnostic workflow of pulmonary hypertension (PH). However, it lacks precision, and right heart catheterization (RHC) may be needed in selected cases. A morbidly obese 47–year–old woman (BMI= 58 Kg/m2) with dyspnea NYHA II was referred to our Center after a high probability of PH was found at echocardiography, this latter performed as a routine assessment before bariatric surgery. Despite a suboptimal acoustic window, the tricuspid regurgitant jet profile was well–defined, with an estimated systolic pulmonary artery pressure (PAP) of 100 mmHg. There were no overt echocardiographic signs of left heart disease. During RHC, mean PAP was just above normal values, with filling pressures at the upper limit of normal (Figure 1), high cardiac index (3.6 L/min/m2) and normal pulmonary vascular resistance (1.4 WU). The echocardiographic estimate of high systolic PAP was explained by an intraventricular RV pressure gradient of about 100 mmHg (Figure 2). Oximetry ruled out a significant intracardiac shunt. Since resting hemodynamics did not explain the patient’s symptoms, the patient pre–test probability of having heart failure with preserved ejection fraction (HFpEF) was intermediate–high, and PAWP was in a grey–zone. Accordingly, we performed an exercise RHC. The test eventually unmasked HFpEF, as witnessed by an abnormal increase of PAWP and LV end–diastolic pressure (Figure 1 panel C and D). Exercise capacity was mildly reduced (71% of predicted) due to peripheral limitation with normal cardiac and respiratory reserves. Transesophageal echocardiography was then performed. It showed a muscular obstruction below the infundibulum dividing the RV into a high–pressure apical portion and a low–pressure infundibulum (Figure 3). This rare congenital anomaly was also associated with a restrictive perimembranous ventricular septal defect. Double–chambered RV has been reported to present rarely in adults, but it might be a cause of false Doppler echocardiographic estimate of PAP. Based on a meticulous invasive hemodynamic characterization at rest and during exercise, integrated with cardiovascular imaging, we could perform such a diagnosis. This congenital anomaly did not fully explain the patient’s symptoms, which may better be attributed to cardiovascular complication of obesity (HFpEF). Accordingly, we referred the patient for bariatric surgery first, postponing the indication to cardiac surgery during the follow–up.

Left atrial volume (LAV) is central to diastolic function evaluation and has demonstrated prognostic value. Guidelines recommend LAV indexation to BSA; however recent studies demonstrate allometric height is superior. Our aim was examine indexation by allometric height and BSA for different ethnicities. Using the World Alliance of Societies of Echocardiography (WASE) normal cohort, subjects with "normal" BMI (18.5-27.5kg/m2 [Asian], 18.5-30kg/m2 [other populations]) were classified by race: White, Black, Asian, or Other. Biplane LAV was indexed to BSA and allometric height; exponents of height for each ethnicity was derived (linear regression of logarithmic transformation of LAV=a(height)b). Indices (heightb) were assessed using Spearman's correlation of LAV/heightb to raw LAV and body size (heightb). 1,366 subjects, (653 female (47.8%), mean age 47±17years; White:524, Black:149, Asian:523 and Other:170) were evaluated. LAV measurements were lowest in the Asian group (mean 41.5±13.4mL vs 49.1±17.0mL White, 50.6±14.3mL Black, 46.7±13.2mL Other; p<0.001). The calculated allometric height exponent for all subjects was 1.87, but varied across ethnicities (2.21 for White, 1.19 Black, 1.14 Asian, and 1.43 Other). The height exponents for each race were good indexation markers; indexed LAV correlated well with raw LAV (r∼1), without overcorrection by the index (r∼0) and was similar to BSA indexation (Figure). Despite normal BMI, there was disparity in LAV indexation across races. With respect to allometric height indexation, different exponents need to be derived based on race. Future validation studies are required in subjects with a wide BMI range.

Abstract Funding Acknowledgements Type of funding sources: None. Background. Right ventricular (RV) systolic dysfunction in patients with left-sided heart disease is known adverse factor. However, the RV adaptation at the different degrees of left ventricular (LV) dysfunction remains to be clarified. Purpose to assess the change in RV contraction pattern in relation to LV ejection fraction (EF) in patients with left-sided heart disease. Methods. LV and RV volumes and EF were measured by 3D-echocardiography in 295 patients with left-sided heart disease (59 ± 17years, 69% male). The 3D meshmodel of the RV was postprocessed by the ReVISION software and its contraction pattern was decomposed along the longitudinal, radial and anteroposterior directions (Fig. A) providing longitudinal, radial and anteroposterior EF (LEF, REF, AEF). Relative contribution of each component to the RV systolic function was measured as the ratio between LEF, REF and AEF and global RVEF (LEFi, REFi, AEFi). Results. Patients with LV systolic dysfunction also had reduced RVEF. Relative contribution of the longitudinal and anteroposterior components decreased, while radial component increased in patients with reduced LVEF (Table). RV LEF and AEF significantly correlated with the LVEF (Rho 0.50 and 0.51, p < 0.0001), while the correlation between REF and LVEF was weak (Rho 0.22, p = 0.0002). There was a significant drop in LEF and AEF (Fig. B) and their relative contribution to the total RVEF (Fig. C) starting from the earlier stages of LV dysfunction. However, it was effectively compensated by significant increase in the radial RV component resulting in preservation of total RVEF in those with normal, mildly and moderately reduced LVEF (50 [46;54] vs 47 [44;52] vs 46 [42;49]%), whereas total RVEF dropped significantly only in severe LV dysfunction (30 [25;39]%; p < 0.0001) (Fig. D). Conclusions. The longitudinal and anteroposterior RV contraction was related to the LVEF and decreased from early stages of the LV systolic dysfunction. Increase in the radial component compensated for the loss of longitudinal and anteroposterior RV components in mild and moderate LV dysfunction to maintain total RVEF. Drop in all three components resulted in significant reduction of total RVEF in severe LV dysfunction. Characteristics of study population Overall (N = 295) LVEF≥50% (N = 166) LVEF < 50% (N = 129) LV EF, % 49.6 ± 14.3 59.9 ± 5.6 36.4 ± 10.9* RV EF, % 46.5 ± 9.2 49.8 ± 6.9 42.3 ± 10.0* RV LEFi 0.42 ± 0.09 0.45 ± 0.09 0.38 ± 0.09* RV REFi 0.47 ± 0.1 0.45 ± 0.1 0.50 ± 0.09* RV AEFi 0.39 ± 0.08 0.41 ± 0.08 0.37 ± 0.07* *p < 0.0001 Abstract Figure.