Echocardiographic Data Research Articles

Machine-learning phenotyping of patients with functional mitral regurgitation undergoing transcatheter edge-to-edge repair - the MITRA-AI study

Abstract Background Severe functional mitral regurgitation (FMR) may benefit from transcatheter mitral valve repair (TMVR), but selection of patients remains to be optimised. Objectives The aim of this study was to use Machine-Learning (ML) approaches to uncover concealed connections between clinical, echocardiographic, and hemodynamic data associated with patients' outcomes. Methods Consecutive patients undergoing TMVR from 2009 to 2020 were included in the MITRA-AI registry. Eleven relevant clinical and echocardiographic variables were selected in a clustering-based model. The primary endpoint was a composite of cardiovascular death or heart failure hospitalisation at one year, while its single components were secondary endpoints. External validation was performed on the Mitrascore dataset and comparison between clustering and Mitrascore was performed with Net Reclassification Index (NRI). Moreover cluster assignment was performed also on a cohort of patients with moderate-to-severe MR treated with medical therapy alone. Results 822 patients were included in the derivation cohort. The composite primary endpoint occurred in 250 (30%) patients. Four clusters with decreasing risk of the primary endpoint were identified (42%, 37%, 25% and 20% from cluster 1 to cluster 4, respectively). Clusters were combined into a high-risk (clusters 1 and 2) and a low-risk phenotype (clusters 3 and 4). High-risk phenotype patients had larger LVs (> 107 ml/m2), lower LVEF (< 35%) and more prevalent ischemic aetiology (51% to 60% vs. 30% to 40%) compared to low-risk phenotype patients. Moreover, within the high-risk group, patients with diabetes mellitus and with advanced age were at increased risk. Within the low-risk group, ischemic aetiology increased the risk of cardiovascular death, while permanent atrial fibrillation amplified that of HF hospitalizations. In the Mitrascore validation cohort of 1119 patients, incidence of the primary end point varied consistently (48%, 52%, 35% and 42%). Clustering achieved a NRI in 27% of the patients in the derivation cohort and 7% in the validation group compared to Mitrascore. In the validation group of 207 patients treated medically, the incidence of the primary endpoint decreased from the first to the fourth cluster (53%, 42%, 30% and 30%). Conclusions A ML analysis identified meaningful clinical phenotypic presentations in FMR undergoing TMVR, with significant differences in terms of cardiovascular death and heart failure hospitalizations, confirmed in an external validation cohort. ML phenotyping also discriminated prognosis of medically treated patients with severe MR.Central Figure

Lead-related tricuspid regurgitation: an important phenotype seen through the lens of computed tomography

Abstract Background The imaging diagnostic approach of patients with cardiac implantable electronic devices (CIED)-related tricuspid regurgitation (TR) is undefined. Functional cardiac computed tomography angiography (4D-CTA) provides a complementary role to echocardiography in the evaluation of tricuspid valve (TV) apparatus and right ventricle (RV) remodeling, but the capability to assess lead-leaflet interaction is unknown. Purpose To evaluate the role of 4D-CTA anatomical and morphological diagnostic assessment in a cohort of patients with severe TR and CIED vs those without. Methods Clinical, echocardiographic and CTA data were collected from two quaternary centers for patients with severe TR and a CIED evaluated between January 2017 to October 2023. Functional and morphological CTA information assessed lead-leaflet relationship to divide patients in those with lead-related TR, those with no lead-TR causal relationship, and those with severe isolated TR but without CIED. Primary end-point was the occurrence of all-cause death. Results A total of 143 patients were identified, roughly dividng the cohort into thirds. Baseline characteristics and imaging characteristics of these 3 groups revealed important differences suggesting a more advanced patophysiology phenotype for those with lead-related TR, particularly presenting both the largest 4D-CTA-derived TV maximum coaptation gap and anatomical regurgitant orifice area (see Figure 1). At regression analysis, time from CIED implantation (OR 1.01, CI 1.00-1.09, p=0.031) and >3 leaflets valve morphology (OR 2.90, CI 1.01-8.32, p=0.040) were independently associated with lead-related TR. After a median follow-up of 18 months, the primary end-point occurred in 36 patients (25%) and was more common among patients with lead-related TR (p-value overall= 0.007, see Figure 2). While no differences in the rate of TV intervention were found, excessive mortality persisted for lead-related TR group even after adjustement for age and gender (HR 6.49, CI 1.72-14.47, p=0.006). Conclusion Systematic 4D-CTA in patients with severe TR and presence of a CIED, identified a large number of patients with lead-related TR with important functional and anatomical implications including greater TR severity and > 3 leaflets. These findings appear to have prognostic relevance that might have decision-making implications for patient management.Figure 1Figure 2

Changes in peak oxygen consumption on excercise and cardiomyopathy disease stage in Fabry disease

Abstract Background Fabry disease (FD) is an X-linked lysosomal storage disorder manifesting as deficiency in the enzyme α-Galactosidase A (1) resulting in multi-organ accumulation of globotriaosylceramide (Gb3) (2) This causes predominantly cardiac, renal and cerebrovascular manifestations. Shortness of breath and exercise intolerance are common and can be related to multiple underlying mechanisms. Cardiopulmonary exercise testing (CPEX) quantifies aerobic fitness, functional capacity, chronotropic and haemodynamic response to exercise, and attributes effort intolerance to different aetiologies, including impaired cardiac and respiratory function. Purpose We hypothesise that there is progressive effort intolerance that reflects continual cardiac Gb3 accumulation, becoming common during myocardial hypertrophy and disabling in the fibrosis and inflammation stage. The aims of this study were to ascertain frequency and severity of exercise intolerance in FD by investigating the relationship between peak maximal oxygen uptake (VO2 max) and cardiac disease stage, quantified based on a four-point scale, as proposed in published literature (3). Methods This was a retrospective review of adults with FD and exercise intolerance attending a specialist clinic who had undergone either CPEX or six-minute walk testing (6MWT) in those less mobile. Biochemical, cardiac magnetic resonance (CMR) imaging and transthoracic echocardiographic (TTE) data were also collected. Results N=54 patients underwent CPEX and N=35 patient underwent 6MWT. Estimated peak VO2 max was calculated using 6MWD in those undergoing 6MWT. Median age was 54 (IQR 40-62) years and 53% were male. Patients were equally distributed across disease stage (1-4). There were significant trends in age (increasing) and gender (male predominance) from stage 1-4. Age/sex-normalised peak VO2 max values were calculated as per published literature due to the confounding effect of age and male gender. Mean normalised VO2 max was 35.5ml/kg/min for the cohort, an underperformance of 12.3 ± 8.0 ml/kg/min. The magnitude of underperformance began from stage 1 (no cardiomyopathy) and increased with each stage (Figure 1). Impairments in renal (creatinine and albumin: creatinine ratio) and cardiac biomarkers (troponin and N-terminal pro brain natriuretic peptide) was associated with reduced VO2 max (Table 1). Increased indexed left ventricular mass on CMR and impairments in atrial volume and function on TTE were also associated with a reduction in VO2 max (Table 1). Conclusion This study is the first of its kind to demonstrate impairments in peak aerobic capacity in adults with FD and no cardiomyopathy (stage 1) which impairs further with cardiac disease stage. Future work should focus on how disease-modifying therapy can target this using VO2 as an endpoint and marker of response.Normalised peak VO2 max + disease stageVO2 max and blood / imaging parameters

Impact of real-world off-label dose of Apixaban on long-term clinical outcomes in patients with atrial fibrillation and chronic kidney disease

Abstract Background Apixaban represent one of the cornerstone treatments to prevent cardioembolic events in patients with nonvalvular atrial fibrillation (NVAF). However, the choices of Apixaban dose guided by the decision-making process of the physician, which considers specific according to kidney functions are inconsistent in the real-world practice. Objective The objective of the present study is to evaluate the effects of real-world Off-label dose of Apixaban on long-term clinical outcomes in NVAF patients with chronic kidney disease (CKD). Methods Our database of AF patients diagnosed with CKD from 2018 to 2023 was used to obtain laboratory, echocardiography, electrocardiogram (ECG), and clinical outcomes data. Inclusion criteria were all AF patients with CKD using Apixaban. And we compared bleeding, systemic thrombotic events including stroke/systemic embolism and death according to off-label real -world dose of Apixaban. Results Among 635 patients with AF and CKD (76.9±10.4 years), 335 (52.8%) patients took off-label underdosed Apixaban. Difference in the baseline characteristics was not observed among patients including CHA2DS2 VASc score and HASBLED score. During the median 18-month follow-up, a lower incidence of bleeding events (P=0.001) was observed in the off-label underdosed Apixaban group compared to those with standard dose or off-label overdosed Apixaban. However, there was no significant difference of systemic thrombotic events including stroke/systemic embolism and death according to off-label real-world dose of Apixaban (off-label underdose vs. standard dose, P=1.000; off-label overdose vs. standard dose, P=1.000; off-label underdose vs. off-label overdose, P=0.609). In multivariate analysis, HASBLED score was independent risk factors for bleeding events (OR 9.650; CI 1.998-46.622; P=0.005). Conclusions Compared with standard or off-label overdose of Apixaban, off-label underdose of Apixaban was associated with a lower risk of bleeding in patients with AF and CKD, with no difference in the risk of stroke/systemic embolism or death, supporting the apixaban dosing tailored to specific clinical features and drug pharmacokinetics of the Asian patients.

Mildly elevated left ventricular outflow tract gradients are associated with increased short term mortality in inpatients without septal hypertrophy

Abstract Background The significance of left ventricular outflow tract gradients (LVOTG) on the clinical outcomes of hypertrophic cardiomyopathy (HCM) has been well studied. An LVOTG of ≥ 30 mmHg is considered significant. However, mildly elevated LVOTG at rest in individuals without basal septal hypertrophy is sometimes encountered in the echocardiography laboratory and data on its association with survival in this group is lacking. Purpose Here we explore the association between LVOTG and short term all cause mortality in inpatients without basal septal hypertrophy. Methods We retrospectively reviewed 47,866 consecutive inpatients who had an echocardiography study during their hospital stay between March 2010 and February 2021 . After excluding cases with incomplete data (10,882) and patients with basal septal hypertrophy > 12 mm (9,486), we remained with 27,498 patients. Demographic, baseline clinical and echocardiographic characteristics were derived from electronic records. Mortality data was validated against the ministry of health national records. A binary logistic regression model for predicting 30-day mortality according to LVOTG dichotomized at each point was used. Then we divided the cohort into 4 LVOTG groups (0-6, 6-10, 10-20 and > 20 mmHg) and the same regression model was used to compare between the groups. Results The mean age in our cohort was 66 ± 17 years and 54% were male. The mean LVOTG was 4.2 ± 2.4 mmHg (Median 4 (IQR=3-5) and the mean left ventricular ejection fraction was 55 ± 9%. A binary logistic regression model showed that when different LVOTG cut-points were used, even a mildly elevated LVOTG predicted short-term survival in this population (figure 1). We then divided our cohort into 4 groups based on LVOTG. There were 24,703 (90%) patients in group 1, 2549 (9%) in group 2, 201 (1%) in group 3 and 25 (0.1%) individuals in group 4. Patients in groups 1 and 2 were younger, had higher hemoglobin levels, lower C-reactive protein (CRP) levels, mildly lower septal thickness, and lower left ventricular ejection fraction compared to the groups with higher LVOTG (table 1). We then applied the same multivariate binary regression model to predict short term mortality with group 1 as a reference. The hazard ratio (HR) for group 2 was 1.3 (CI 95%: 1-1.6, p=0.03), for group 3 HR=2.8 (CI 95%: 1.6-5.1, p<0.001) and for group 4 HR=2.8 (CI 95%: 0.6-12.8, p=0.18). Conclusions We have shown in a large cohort of inpatients without basal septal hypertrophy that a mildly elevated rest LVOTG (6-10 and 10-20 mmHg) predicted all cause 30-day mortality. Patients in the elevated LVOTG groups were older with lower hemoglobin and higher CRP levels, but LVOTG remained an independent predictor in a multivariate regression model. This could potentially aid early detection of at-risk populations.Mortality at different LVOTG cut-pointsBaseline characteristics

Impact of Pirfenidone on arrhythmic and clinical outcomes in patients with idiopathic pulmonary fibrosis

Abstract Background Atrial fibrosis is an important substrate in atrial fibrillation (AF), particularly in the setting of structural heart disease. Previous study reported that pirfenidone, an antifibrotic agent, was beneficial at reducing myocardial fibrosis. The objective of the present study is to evaluate the effects of pirfenidone on arrhythmic and clinical outcomes in patients with idiopathic pulmonary fibrosis (IPF). Methods Our database of patients diagnosed with IPF from 2008 to 2023 was used to obtain echocardiography, electrocardiogram (ECG), and 24hr-holter monitoring data. Inclusion criteria were all IPF patients with/without Pirfenidone. And we compared arrhythmic events including atrial fibrillation, atrial premature complex, atrial tachycardia, ventricular arrhythmia and clinical outcomes according to use of Pirfenidone. Results Among 257 patients with IPF (74.0±8.9 years), 106 (42.1%) patients took Pirfenidone. Difference in the baseline characteristics was not observed. During the median 36-month follow-up, a lower incidence of arrhythmic events (P=0.001) and diastolic dysfunction (P=0.025) was observed in the Pirfenidone group. In univariate analysis, hypertension, coronary artery disease, higher body weight, longer PR interval, QRS duration, and less use of Pirfenidone were associated with arrhythmic events. In multivariate analysis, higher body weight and less Pirfenidone use were independent risk factors for arrhythmic events. Conclusions The use of Pirfenidone was associated with less arrhythmic events and lower diastolic dysfunction compared with no use of Pirfenidone in the long-term follow-up. And obesity was associated with higher incidence of arrhythmic events in IPF patients.

Left ventricular mass index and prognosis of symptomatic severe aortic stenosis in women and men

Abstract Background Symptomatic severe aortic stenosis (AS) requires surgical (SAVR) or transcatheter aortic valve replacement (TAVR), and many patients are on the procedure waiting list. The diagnosis of severe AS is based on clinical and echocardiographic criteria, such as left ventricular ejection fraction (LVEF), aortic valve area (AVA), mean transvalvular gradient, and peak aortic jet velocity. However, there is a gap in knowledge regarding the influence of left ventricular mass on the prognosis of these patients, especially considering differences between women and men. Purpose To evaluate the influence of left ventricular mass index (LVMi) on the mortality of women and men with severe AS awaiting SAVR or TAVR. Methods A prospective study analysed the death rate in 531 outpatients with symptomatic severe AS with mean transvalvular gradient ≥40 mmHg, AVA ≤1.0 cm2, or peak aortic jet velocity ≥4.0m/s at echocardiography with the indication for TAVR or SAVR in the period from April 2020 to February 2024. Baseline data included analysis of clinical characteristics, echocardiographic variables, and the presence of coronary artery disease (CAD). Statistical analyses were performed using the Kaplan-Meier (K-M) and Cox proportional hazards methods to analyze mortality rates in women and men. Results The mean age was 74.7±11.6 years, with 283 (53.3%) men. Over a follow-up period of 2.67±1.22 years, death occurred in 165 (31.1%), 148 (86%) due to cardiovascular disease, and 152 (92%) had heart failure (HF) NYHA II to IV, 51 (9,6%) had angina, and syncope in 11 (2.1%) of the patients. Patients who died had lower LVEF (61.4%±8.9% vs. 58.8%±10.8%; p=0.008) and higher LVMi (125.3±32.5 g/m2 vs. 115.5±29.3 g/m2; p=0.001). Angina, syncope, hypertension, dyslipidemia, diabetes, smoking, atrial fibrillation, and CAD prevalence were similar in living patients and in those who died. Both groups had similar echocardiographic data, such as left atrial volume, mean transvalvular gradient, and peak jet velocity. TAVR and SAVR were done in 111 (20.9%) and 162 (30.5%) patients. Of these, 21 (18.9%) and 20 (12.4%) died during follow-up, respectively. Cumulative mortality of all patients was higher with LVMi >115 g/m2 compared to ≤115 g/m2 (p=0.008)(Figure). In women but not in men, cumulative mortality was higher with LVMi >115 g/m2 compared to ≤115 g/m2 (p=0.046). Cox multivariate analysis, adjusted for LVEF, LVMi, CAD, and age, showed LVMi as an independent variable for death [HR=1.50 (95%CI: 1.10-2.05); p=0.011]. LVEF [HR=0.97 (95%CI: 0.95-0.99); p=0.009] and LVMi [HR=1.75 (95%CI: 1.10-2.79); p=0.016] were independent variables for death in women, but not in men. Conclusion Women with higher LVMi and lower LVEF should have valve intervention prioritized.Figure

Effects of cardiac resynchronization therapy and physiologicaL pacing on left atrioventricular coupling index: the REPHYL-LACI study

Abstract Introduction Cardiac dyssynchrony and right ventricular pacing are associated with left atrial (LA) remodeling and atrioventricular uncoupling. Cardiac resynchronization therapy -CRT and conduction system pacing –CSP are important therapeutic options. Left atrioventricular coupling index (LACI) is a novel imaging parameter useful to describe the relationship between LA and left ventricle (LV). It could be measured as the ratio between LA end-diastolic volume (EDV) and the LV EDV or, alternatively, as the LA volume indexed for body surface area (LAVi) divided for a’ measured by tissue Doppler imaging (TDI) at medial mitral annulus level. Higher values indicate greater impairment of atrioventricular coupling. However, LACI has not been investigated in patients treated with CRT or CSP, and there is no comparison data about the two different measurement methodologies with echocardiography. Purpose To study the effects of CRT/CSP on LACI. Methods We retrospectively collected clinical, ECG and echocardiographic data of patients treated with standard CRT or CSP. Changes between baseline and follow-up (i.e. before and after CRT/CSP) were tested for significance. Baseline features were compared with these of a control group of patients without established major cardiovascular diseases. Results We enrolled fifty-six patients (median age at first echo 78[72.5-82]years; males 70%) and 56 controls (median age 77[72.5-83]years, p=0.974; males 57%, p= 0.170). Main clinical/instrumental data are shown in Table 1 and 2. In patients treated with CRT/CSP baseline LACIv (LAVid/LV EDV) was significantly lower than in controls (31[21-44]%vs34[29-48]%, p=0.040), despite higher LAVi and LV volumes in the first group (p<0.0001 for both). Conversely, LACId (LAVi/TDI-a’) was significantly higher in the CRT/CSP (4.48[2.81-8.28]vs2.89[2.36-3.67]mlxsecond/cm-1, p<0.0001). After a median follow-up of 515[282-1326]days, patients treated with CRT/CSP showed a significant increase of both LACIv (40[29-50]%, p=0.004) and LACId (4.95[3.77-9.89], p<0.0001). This worsening of atrioventricular coupling was accompanied by a trending LA dilatation with significant reduction of its reservoir function compared to baseline (expansion index 0.58[0.38-1.30]vs0.43[0.29-0.58], p=0.0002), despite a tendency toward stability or improvement of LV size and systolic/diastolic parameters. Conclusions In patients treated with CRT/CSP there is a worsening of LACI over time. We can speculate that the detrimental effects of artificial pacing might not be adequately counterbalanced by CRT/CSP, or that LV and LA pathology follow alternative trajectories with different responses to treatments. Moreover, the measurement of LACId should be probably avoided in patients with conduction disorders or paced. Further larger case-control studies are needed to clarify the usefulness of LACI as a valid parameter to assess atrioventricular coupling and its changes over time in patients treated with CRT/CSP.

Echocardiographic insights redefining risk in pulmonary arterial hypertension: a focus on right atrial volume index for enhanced stratification

Abstract Introduction In Pulmonary arterial hypertension (PAH), the right atrium plays a critical role, and its size, determined by echocardiography, is crucial for risk stratification. Despite this, current guidelines still prioritize right atrial area (RAA) over the right atrial volume index (RAVI). This approach is contrary to the recommendations of international echocardiography societies since 2016, which advocate for the use of RAVI for a more accurate assessment. Purpose Identify the RAVI value corresponding to the RAA, in PAH risk stratification used in the 2022 ESC guidelines. Methods We conducted a retrospective analysis of all consecutive patients of a single-center, since 2002. Patient's echocardiograms were revised for simultaneous assessment of RAA and right atrial volume index (RAVI). Over an average follow-up of 6.7 years (SD 5.9), we recorded a cohort of 82 patients diagnosed with PAH. From this group, we excluded 27 patients with congenital etiologies, 14 due to the insufficient quality of echocardiographic data, and one patient identified as an extreme statistical outlier. A Pearson's correlation analysis was used to access the correlation between RAA and RAVI for PAH diagnosis. Results A total of 40 patients were included with a mean age at diagnosis of 48.85 years (SD 17.82), predominantly female (77.5 %). The most prevalent etiologies were idiopathic (32.5%) and connective tissue disease-associated PAH (27.5%). Clinical presentations included right heart failure signs in 30% of patients, rapid symptom progression in 12.5%, syncope history in 15% and 77.5% in WHO-FC III-IV. Average 6-MWD and NT-proBNP levels were 392,1 m (SD 120,2) and 1636,18 ng/L (SD 2576,14), respectively. Average hemodynamics parameters were right atrial pressure 7,39 mmHg (SD 4,940); cardiac index 2,28 L/min/m2 (SD 2,06); stroke volume index 3,38 mL/m2 (SD 3,92) and mixed venous oxygen saturation 65,68% (SD 10,86). Average echocardiographic parameters were RAA 20,14 cm2 (SD 4,80); TAPSE/sPAP 0,34 mm/mmHg (SD 0,18) and RAVI 37,78 mL/m2 (SD 13,67), with 10% of pericardial effusion. Statistical analysis revealed a strong and significant correlation between RAA and RAVI (r=0.82, 95% CI: 0.69-0.90, p<0.001). The derived linear relationship is expressed as "y=2.8*X -18". Therefore, an RAA value of 18 cm² translates to a RAVI of 32 mL/m², while an RAA of 26 cm² corresponds to a RAVI of 55 mL/m². Conclusion Our study supports a revision in HAP risk assessment guidelines, suggesting a shift to a more comprehensive approach using right atrial volume index (RAVI) measurements. We propose categorizing risk as low for RAVI < 32 mL/m², intermediate for RAVI between 32 and 55 mL/m², and high for RAVI > 55 mL/m². This recommendation aligns with the standards of international societies and is grounded in best clinical practices, considering that indexing measurements of the right atrium to body size potentially offers greater accuracy than absolute values.

Echocardiographic and clinical features of patients developing prosthesis-patient mismatch after TAVI: insights from an international multicenter registry

Abstract Background The impact of prosthesis-patient mismatch (PPM) after transcatheter aortic valve implantation (TAVI) is controversial. Purpose Our study aims to evaluate the impact of PPM on mortality and clinical-echocardiographic progression of cardiac damage in a "real world" cohort of patients at intermediate and low surgical risk and to characterize its main predictors. Methods 963 patients who underwent TAVI procedure between 2017 and 2021, from an international multicenter observational registry, were included in this analysis. Multiparametric echocardiographic data were analyzed at 1-year follow-up (FU). Clinical and echocardiographic features were stratified by presence of PPM and PPM severity, as per the most current international recommendations (VARC-3 criteria). Results 18% of patients developed post-TAVI PPM, (7.7% of the whole cohort severe). At baseline, 50.3% of patients with PPM were male (vs 46.2% in the cohort without PPM, p=0.33), aged 82y (interquartile range (IQR) 79-85y) vs 82y (IQR 78-86y; p=0.46), and 55.6% had Balloon-Expandable valves implanted (vs 46.8% of patients without PPM, p=0.04); they had smaller left ventricular outflow tract (LVOT) diameter (20mm, IQR 19-21 vs 20mm, IQR 20-22, p=0.02), reduced Stroke Volume index (SVi) (34.2 vs 38 ml/m2, p<0.01) and transaortic flow rate (190.6 vs 211 ml/s, p<0.01). At pre-discharge FU patients with PPM had more paravalvular aortic regurgitation (AR) (moderate/severe AR 15.8% vs 9.2%, p<0.01). At a median FU of 1.46 years (IQR 1-4), there was no evidence of a significant impact of PPM on overall mortality (15.3% vs 13.1%, p=0.46) nor on rehospitalization rate for heart failure (4.3% vs 8.0%, p=0.10). At 1-year FU, maladaptive alterations of left ventricular parameters were found in patients with PPM, with a significant increase in endsystolic diameter (ESD) (33 vs 28mm, p=0.03) and a statistically non-significant increase in LV mass index (121 vs 106g/m2, p=0.07). Interestingly, trajectory parameters of patients with PPM from baseline to 1-year FU showed a reduced cardiac remodeling compared to patients without PPM, including no LVEF improvement (p=0.88), absent reduction of LV end-diastolic volume (p=0.70), indexed LV mass (p=0.31), ESD (p=0.48) and pulmonary artery systolic pressure (p=0.82), and an increase of basal RV diameter (p<0.001). Patients with moderate/severe PPM had worse NYHA functional class at 1 year (NYHA III-IV 13% vs 7.8%, p=0.03). Independent predictor of PPM at multivariable logistic regression was male gender (OR=1.93, p=0.04); while SVi (OR=0.86, p<0.001), prosthetic size >23mm (OR=0.62, p=0.03) and LVOT diameter (OR=0.79, p=0.02) had protective effect. Conclusions There was no evidence of a short- or medium-term impact of PPM on mortality. However, clinical-echocardiographic evaluations demonstrated a PPM-related pattern of early ventricular maladaptive alterations associated with a significant deterioration in NYHA class at 1 year.

Speeding up echocardiographic examination by automated generation of 2D imaging views from 3D volumetric data using machine learning

Abstract Background 3D echocardiographic data contain infinite 2D echocardiographic planes generated by multiplanar reconstruction, but the process is labor-intensive and time-consuming. Artificial intelligence (AI) utilizing cutting-edge machine learning techniques may improve the accuracy and efficiency of the process. In the study, we developed and validated an AI software that automatically reconstructs 7 2D views recommended by the American Society of Echocardiography from 3D echocardiographic data. Method Convolutional neural network (CNN) architecture utilizing Spatial Configuration Net was used as the machine learning model. We identify a minimum of 3 key feature landmarks on each 2D cross-sectional plane, with the 3D coordinates representing 2D cross-sectional planes accordingly. Subsequently, these landmarks are accurately labeled within a 3D space. 31 landmarks were identified across 7 2D cross-sectional planes and a total of 472 3D volume data were labelled. The performance of the model is evaluated by Root Mean Square Error (RMSE) of the predicted landmark coordinates. Results The mean RMSE over 31 predicted landmarks evaluated in testing is 2.70% for the input 3D volume dimensions. The average time used to generate the 7 2D imaging views was 19.91±3.19 seconds (figure). Conclusion The AI algorithm can efficiently convert 3D echocardiographic data into guideline-recommended 2D images, which shortens the length of echo examination but still preserves the accuracy.AI generation of 2D views from 3D echo

Establishing normal global longitudinal strain values in heart transplant patients: a novel approach to enhancing detection of rejection and cardiac allograft vasculopathy

Abstract In the realm of heart transplantation, accurate cardiac monitoring is pivotal for patient outcomes. This study pioneers in filling a critical void by delineating the normative values of Global Longitudinal Strain (GLS), specifically tailored for heart transplant recipients, distinguishing them from the general population. We conducted a retrospective analysis on a cohort of 110 patients who underwent heart transplantation, meticulously compiling echocardiographic data over the first 18 months post-operation. Our research focused on two primary indicators of cardiac function: Ejection Fraction (EF) and Global Longitudinal Strain (GLS). The data indicated that EF values remained within the normal range and relatively stable throughout the monitoring period. In contrast, GLS values exhibited a gradual increase over time, suggesting a post-transplant myocardial adaptation process. However, these GLS values did not reach the established reference ranges for non-transplanted, healthy hearts, highlighting the distinctive physiological landscape of transplant recipients. Our study elucidates the superior sensitivity of GLS in detecting subtle myocardial changes that might precede clinically apparent dysfunction, advocating its utility as a crucial surveillance tool for this demographic. By pinpointing the modified GLS benchmarks applicable to post-heart transplant patients, our findings advocate for a recalibrated echocardiographic assessment protocol. Such a protocol can significantly enhance the surveillance for post-transplant complications, most notably graft rejection and the onset of cardiac allograft vasculopathy (CAV). The study posits that incorporating these refined GLS thresholds into routine post-transplant evaluations could facilitate early intervention, potentially mitigating adverse outcomes and improving the long-term prognosis for heart transplant recipients. Thus, our research underscores the need for updated clinical guidelines that integrate these novel echocardiographic insights, paving the way for improved patient-centric cardiac care in the transplant setting.

Utilizing cluster analysis of biomarkers alongside echocardiographic deformation parameters to forecast the outcome of atrial fibrillation post-ablation

Abstract Background Atrial fibrillation (AF) management often involves catheter ablation, but its recurrence necessitates careful clinical management and potential adjustments in medication or further ablation procedures. This study aims to investigate the predictive value of biomarkers and echocardiographic parameters for early AF recurrence. Methods In the prospective study, we enrolled patients with symptomatic paroxysmal or persistent atrial fibrillation undergoing catheter ablation. Pulmonary vein isolation was performed in every index procedure, with additional ablation or substrate modification as per physician preference. Blood samples were collected from both the atrium and peripheral vein to assess levels of tumor endothelial marker 1 (TEM1), galectin 3, connective tissue growth factor (CTGF), transforming growth factor-beta (TGF-β), C-terminal propeptide of procollagen type I (PICP), and Smad3. Pre-procedural echocardiographic parameters, including the E/e’ ratio, peak atrial longitudinal strain (PALS), and peak atrial contractile strain (PACS), were recorded. Clustering models with sparse canonical association analysis (CCA) were employed to develop predictive models integrating biomarker and echocardiographic data for early atrial fibrillation recurrence. Results Out of 80 prospectively enrolled patients, 68 completed the study, with six cases of early atrial fibrillation recurrence observed. Following dimension reduction and clustering, we found that the combined use of biomarkers and echocardiography significantly predicted atrial fibrillation recurrence (HR: 9.44, p=0.05, 95% CI: 1.0-88.9). Notably, among these parameters, TEM1 biomarker sampled from the peripheral vein (p=0.02), left atrium dimension (p=0.07), and left ventricle dimension (p=0.02) exhibited the most significant predictive power. Conclusions Our study highlights the effectiveness of integrating biomarkers and echocardiography parameters in predicting early recurrence of atrial fibrillation post-ablation in patients undergoing catheter ablation.main_figure

Latent class analysis reveals a novel phenotype of heart failure that spans the left ventricular ejection fraction range

Abstract Background It is increasingly evident that heart failure (HF) represents a heterogenous syndrome rather than a single clinical entity. The elusiveness of effective therapies for heart failure with preserved ejection fraction (HFpEF) has led to a consensus that our current, unidimensional construct of HF using only left ventricular ejection fraction (LVEF) does not adequately capture the multiplicity of the disease states. The ability to harmonize echocardiographic data from multiple sources has enabled use of unsupervised cluster-based analysis to identify multidimensional cardiac structural phenotypes. Purpose To identify cardiac structural phenotypes of HF across the LVEF spectrum. Methods We harmonized echocardiographic data from eight randomized clinical HF trials (ESCAPE, EXACT-HF, FIGHT, I-PRESERVE, NEAT-HFpEF, RELAX, STICH and TOPCAT), which included both HFrEF and HFpEF populations (total n=4223 echocardiograms). These studies collectively spanned the years 2000 through 2015 and represent a balanced LVEF distribution. Latent class analysis (LCA) was performed iteratively to identify predominant structural phenotypes using LVEF, RV function, LV end diastolic volume, LV mass index, eccentricity, mitral valve deceleration time, and lateral E/e’ ratio. Results LCA identified 4 echocardiographic phenotypes. Three phenotypes skewed toward either high or low EF, but one phenotype demonstrated a relatively even distribution of patients with HFrEF, heart failure with mildly reduced ejection fraction (HFmrEF) and HFpEF (36.0%, 21.4% and 42.7%, respectively). Patients in this phenotype had preserved RV function and left ventricular hypertrophy (97%), of which 56.8% had concentric and 43.2% eccentric LVH. E/e’ was normal in 63% of subjects. A vast majority (91%) of patients had recent-onset HF (diagnosed within the past year). There were no remarkable distinguishing comorbidities. Notable differences in biomarker profile included higher levels of troponin I, cyclic GMP and lower levels of neurohormones (aldosterone, endothelin-1, dopamine, and norepinephrine) than the other phenotypes. Conclusions This is the first cluster-based analysis to identify a quantitative structural HF phenotype of HF that is not distinguished by LVEF. While the underlying pathophysiology is unclear, most patients have recent onset HF and biomarker profiles with relatively low neurohormone activity. These features may reflect a distinct pathophysiology that could indicate a specific, targeted intervention.

Aortic valve tract dynamics in normal-flow low-gradient and normal-flow high-gradient severe aortic stenosis

Abstract Introduction Aortic stenosis (AS) is the most common valvular heart disease in developed countries. Severe AS is defined as a mean pressure gradient (MG) ≥ 40 mmHg, a maximum aortic jet velocity≥4 m/s and an aortic valve area (AVA)≤1 cm2. However, classification of AS severity may be challenging due to discordant results on echocardiography. The normal-flow low-gradient severe AS (NFLG-AS) is defined as AVA≤1 cm2, MG<40 mmHg, left ventricular ejection fraction ≥ 50%, and stroke volume index (SVi) ≥ 35 ml/m2, whereas in the presence of MG > 40mmHg the condition is described as normal-flow high-gradient AS (NFHG-AS). Purpose The purpose of this study was to seek differences in the dynamic changes of the aortic valve tract throughout the cardiac cycle between the two clinical entities: NFHG-AS (Group 1) and NFLG-AS (Group 2). Methods In total, 130 patients with normal flow severe AS who underwent TAVI and had 3D transoesophageal echocardiographic data sets were screened. 38 patients with NFHG-severe AS and 40 patients with NFLG-severe AS with matching clinical characteristics and aortic valve area were identified. A custom-made semi-automated application developed by SQ was used. The application allows tracking of the aortic valve tract surface throughout the cardiac cycle in 3D transoesophageal echocardiograms and provides measurements of the geometrical planes at 4 levels: left ventricular outflow tract (LVOT), aortic annulus (AoA), sinuses of Valsalva (SoV) and sinotubular junction (STJ). Results The echocardiographic characteristics and the dynamic changes of the aortic valve tract between the two groups are shown in Tables 1 and 2. Both groups had comparable echocardiographic characteristic apart from the mean aortic valve pressure gradient as expected. With regards to the aortic valve tract geometrical dynamic changes, the relative LVOT and AoA area changes were bigger in Group 1 (36.8±15.9% vs 29.1±11.9%; p=0.017 and 21.0±8.39% vs 17.1±6.6%; p=0.028). The SoV and STJ relative changes were similar between the two groups. The same applies to aortic stiffness parameters, namely compliance and distensibility of the ascending aorta, systemic arterial compliance, and valvulo-arterial impedance. Conclusion The LVOT and aortic annulus area demonstrate more prominent dynamic changes in patients with normal-flow high-gradient severe AS compared to individuals with normal-flow low-gradient severe AS. While the SoV and the STJ geometry does not change significantly through the cardiac cycle, a more elastic outflow tract allows larger expansion in systole and higher pressure gradients across the aortic valve, whereas a stiffer outflow tract and annulus result in lower pressure gradients, despite the presence of severe aortic stenosis (AVA<1.0cm2). These differences in dynamic LVOT and aortic annulus changes may explain the discrepancy between aortic valve area and pressure gradients in patients with normal-flow low-gradient AS.

Sex differences in diastolic function following myocardial infarction on doppler echocardiography

Abstract Background Whilst females have relatively greater preservation of left ventricular ejection fraction (LVEF) following myocardial infarction (MI), they have higher rates of heart failure, presumably due to diastolic dysfunction (DD). Objectives This study sought to assess sex differences in LV diastolic function on Doppler echocardiography following MI. Methods Data on 2505 consecutive patients with a first-ever MI were included. Echocardiography was performed within 24 hours of admission. Significant DD was defined as grade 2+3 DD according to current ASE/EACVI guidelines. Diastolic function score (DFS) was calculated by summing the number of abnormal parameters out of the 4 key diastolic parameters (e’ velocity, E/e’ ratio, left atrial volume index [LAVI], tricuspid regurgitation velocity [TRV]). Results Compared to males, females were older, had greater co-morbidity, less 3-vessel disease, and a higher LVEF (55.0+9.8% versus 52.7±9.8%, p<0.001). LAVI, e’ velocity, E/e’ ratio, significant DD and DFS were significantly associated with female sex on univariate group comparisons. In multivariable models incorporating clinical, angiographic and echocardiographic data to determine independent predictors of diastolic parameters, female sex was independently associated with abnormal LAVI (OR 1.42, p=0.013), E/e’ ratio (OR 2.86, p<0.001), TRV (OR 1.83, p=0.005), significant DD (OR 2.12, p<0.001) and DFS (OR 2.60, p<0.001). Conclusions Female sex is a strong independent correlate of diastolic dysfunction on Doppler echocardiography in patients with a first-ever MI. This may explain the higher incidence of heart failure despite relatively preserved LVEF in females following MI.

Speckle tracking echocardiography as a predictor of location of ablation sites in candidates to catheter ablation for recurrent ventricular tachycardia

Abstract Background Preoperative imaging is essential before a ventricular tachycardia (VT) ablation procedure, to improve operative outcomes and reduce procedural times. Although MRI is the gold standard, it has several limitations, including patient compliance, possible presence of non-MRI-compatible devices, and long acquisition time. Speckle tracking echocardiography (STE) is a reliable and appealing technique that quantifies regional and global myocardial deformation, as well as layer-specific (endo-, mid- and epicardial) longitudinal strain, without MRI limitations. Purpose This study aimed to evaluate the efficacy of STE in predicting VT ablation sites. Methods In this study, we compared the bull’s eye segmentation of the left ventricle, global and layer-specific, obtained with STE (TomTec Arena), to investigate whether echocardiography can predict the areas of scar and late potential, as identified by electroanatomic mapping (EnSite X mapping, HD Grid mapping catheter, Abbott). Strain analysis and electroanatomic mapping data were matched segment-by-segment to obtain pairs of endocardial strain and bipolar substrate maps, as well as pairs of midmyocardial/epicardial strain and unipolar substrate maps. Results Twenty-three consecutive patients with an indication for catheter ablation for recurrent VT were enrolled. All patients were being treated with beta-blockers, 52% were taking amiodarone, and only 2 patients were on mexiletine. A total of 1170 pairs of bull’s eye segments were available for analysis. A binary logistic mixed-effects model was used to predict the presence of electroanatomical scar based on strain echocardiography data, to account for interpatient variability. The study findings highlighted a close correlation between the bipolar map and endocardial strain values, and between the unipolar map and midmyocardial strain values. Progressively higher (less negative) values of endocardial strain proved predictive of bipolar electroanatomical scar, with an increase in the odds ratio of bipolar electroanatomical scar equal to 6.2% (95% confidence interval 2.5%-10%) for each unit increase in strain values. Similarly, progressively higher values of midmyocardial strain were predictive of unipolar electroanatomical scar, with an increase in the odds ratio of unipolar electroanatomical scar equal to 6.2% (95% confidence interval 1.2%-11.4%) for each unit increase in strain values. Conclusions The data from our study showed an anatomical correspondence between the areas of low potential identified by electroanatomical mapping and the areas of anomalous longitudinal strain. In particular, the endocardial strain correlates with the bipolar map, and the meso-epicardial strain correlates with the unipolar map. These data may prove useful in the appropriate planning of the procedure in patients with an indication for catheter ablation in the context of recurrent VT.

Revisiting echocardiographic ranges of left ventricular end-diastolic volume index: an analysis of the discrepancies between the 2006 and the 2015 recommendation for chamber quantification guidelines

Abstract Background Indexed left ventricular end-diastolic volume (LVEDVi) and indexed left ventricular end-diastolic diameter (LVEDDi) serve as crucial parameters indicative of left ventricle (LV) size. The "Recommendations for Chamber Quantification" guideline was published in 2006 and updated in 2015. While the previous guideline maintained uniform cut-off points for both men and women, the latest revision introduced new thresholds that vary between genders. Purpose The study's primary aim is to evaluate the extent of change in labeled indexed LV diastolic volumes in men and women following the adoption of the 2015 guidelines and identify potential contributing factors to this change. Methods In this cross-sectional study, we analyzed echocardiography data extracted from a web-based registry from March 2020 to October 2022. LV volume variables were categorized based on the indexed ranges specified in the 2006 and 2015 guidelines. Statistical analysis was performed using SPSS version 25. Results Among the 7598 individuals, the classification of LVEDDi according to the 2006 and 2015 guidelines differed in 456 (6.1%) subjects. The classification of LVEDVi differed in 910 (12.0%) individuals. In 213 (5.5%) female subjects initially categorized as having normal or mild LV enlargement according to the 2006 guideline, there was substantial reclassification following the application of the 2015 recommendation (i.e., transitioned from a normal classification to moderate LV enlargement and from mild to severe LV enlargement). All females classified as having moderately abnormal LVEDVi according to the 2006 guideline were reclassified as having severely abnormal LVEDVi according to the 2015 guideline. Conclusion The significant disparities observed in the classification of indexed LV volumes between the 2006 and 2015 guidelines underscore the importance of ongoing dedicated research to reassess the range of indexed echocardiographic parameters, considering various outcomes and differences in countries and races.

Relationship between NT-proBNP, echocardiographic abnormalities and functional status in patients with subclinical diabetic cardiomyopathy

Abstract Background Persons with diabetes are at risk for developing a cardiomyopathy through several pathophysiological mechanisms independent of traditional risk factors for heart failure. Among those with so-called diabetic cardiomyopathy (DbCM), the relationship between natriuretic peptides, cardiac structural abnormalities and functional capacity is largely unknown. Purpose This study aimed to evaluate associations between NT-proBNP concentrations, clinical characteristics, echocardiographic findings, health status and activity, and outcomes from cardiopulmonary exercise testing Methods The Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure Trial (ARISE-HF) trial is evaluating the effects of AT-001, a novel aldose-reductase inhibitor in participants with DbCM without a prior history of heart failure (1). Participants were included if they had a known diagnosis of type 2 diabetes and age ≥60 (or ≥45 with a duration of diabetes of ≥10 years or estimated glomerular filtration rate ≤60 mL/min/1.73m2). Participants were required to have evidence of one of: structural cardiac abnormality, elevated cardiac biomarkers, or impaired exercise tolerance, defined as a peak oxygen uptake (VO2) ≤75% of predicted. In this prespecified subgroup analysis of the ARISE-HF trial, 685 participants with baseline echocardiography data, laboratory investigations, and functional assessment were included. Participants were stratified by N-terminal pro-B type natriuretic peptide (NT-proBNP) quartiles, and correlation with echocardiographic and functional parameters were assessed using Spearman correlation test. Results The mean age of participants was 67.4 years and 50% were female. The mean duration of type 2 diabetes was 14.5 years with a mean hemoglobin A1c of 6.98. The median NT-proBNP was 71 (Q1, Q3: 33, 135) ng/L. No association was observed between NT-proBNP concentrations and echocardiographic parameters of either diastolic or systolic dysfunction including global longitudinal strain, left ventricular ejection fraction, left ventricular mass index, left atrial volume index, E/e’, or right ventricular systolic pressure (Figure 1). In contrast, NT-proBNP was significantly correlated with components of the Kansas City Cardiomyopathy Questionnaire (P<0.001), the Physical Activity Scale in the Elderly (P=0.004), duration of cardiopulmonary exercise testing (P<0.001), peak VO 2 (P<0.001), and ratio of minute ventilation/carbon dioxide production (P=0.002; Figure 2). Conclusion Among highly selected patients with subclinical DbCM, elevated NT-proBNP concentrations are associated with worse health status, lower activity levels, and reduced functional capacity, but not with cardiac structural abnormalities. These findings suggest that regardless of cardiac structural abnormalities, biomarker concentrations reflect important deterioration in functional capacity in affected individuals.

Assessing boundary conditions in CFD for transvalvular pressure gradient calculation in cardiac hemodynamics

Abstract Background Computational fluid dynamics (CFD), which has the advantages of providing detailed pressure distribution, has been widely used for cardiac function assessment and heart disease diagnosis. However, the results are usually influenced by the boundary conditions. Particularly, the transvalvular pressure gradient, which serves as a crucial indicator for mitral stenosis and the efficacy of mitral valve surgery, can easily be miscalculated. Here, we assess the effects of widely used boundary conditions on the transvalvular pressure gradient computed based on the Bernoulli equation and the line probe, respectively. Purpose This study aims to determine the effects of boundary conditions on the transvalvular pressure gradient in CFD. Methods We constructed cardiac models including left atrium, left ventricle, aorta from CT and mitral valve from transesophageal echocardiography data (Figure 1). The intraventricular flow fields were computed using CFD tool with four different boundary conditions (BC) at the same cardiac output. BC1 involved specifying the total flow rate of the aorta, with zero pressure at the entrance of the pulmonary veins. BC2 maintained equal flow rates at the entrances of the pulmonary veins. BC3 followed Murray's law, where the flow rate ratio in the pulmonary veins is proportional to the 1.5 power of the area ratio. BC4 followed Poiseuille's law, where the flow rate ratio is proportional to the square of the area ratio. The results encompassed the mean transvalvular pressure gradient and peak transvalvular pressure gradient obtained through the Bernoulli equation and the line probe methods, respectively. Results Figures 2(A-D) present the contours of transvalvular pressure under peak flow velocity conditions and the isosurfaces of vorticity within the ventricle. The results show that the pressure within the atrium is notably lower in the BC2, leading to a 63% underestimation in the mean transvalvular pressure gradient and a 22.9% deviation in the peak transvalvular pressure gradient (Figure 2 F). The transvalvular pressure gradient for BC1, BC3, and BC4 do not exceed 10%. The results reveal that the pressure distribution and vorticity within the ventricle are consistent, primarily due to the influence of the mitral valve. Conclusion When evaluating transvalvular pressure gradient using CFD, it is crucial to specify appropriate boundary conditions. Using inappropriate boundary conditions may lead to underestimation of the transvalvular pressure gradient, thereby affecting further diagnostic decisions. In research studies, it is recommended to allocate flow in different branch vessels according to Murray's law, where the flow in different branch vessels is proportional to the 1.5 power of the vessel cross-sectional area.Modelling flow chartTransvalvular pressure gradient