Body Surface Research Articles

Sex differences in aortic prognosis in Marfan patients, a retrospective longitudinal study from the REPAG registry

Abstract Introduction Previous studies(1-4) have suggested a more favourable aortic outcome among women with Marfan syndrome (MFS), although the precise underlying mechanism remains not completely understood. In this retrospective longitudinal study, we aim to evaluate sex differences in aortic events in a large cohort of Marfan patients seen in 11 tertiary centres in Spain. Methods Patients with diagnosis of Marfan syndrome (MFS) were included. Data on aortic events (AE) including elective aortic surgeries, acute aortic syndrome or death were incorporated. Survival free of the combined endpoint of death or first aortic event (elective aortic surgery or acute aortic syndrome) was compared between male and female by the Kaplan-Meier curves, log-rank test and subsequent Cox regression analysis. Results A total of 442 patients with MFS where included, 48.2% female and 56.2% index cases. Although systemic score and proband proportion was not different between both sexes, the diagnosis was earlier in males (p=0.01) (Table). Furthermore, among adult patients, males exhibited greater height, weight, and body surface area (BSA). Absolute aortic root diameter at baseline was greater in males, but not BSA-indexed diameters or z-scores. Combined endpoint of death or aortic event was observed in 192 patients (120 male, 72 female, p=<0.00001). Female sex had better survival free of the combined endpoint in a multivariable Cox analysis (HR 0.41 95% CI=0.30–0.55) with a mean survival free of the combined endpoint of 41.3yrs in male and 61.4 years in females (p<0.0001) (Figure).Although a higher proportion of elective aortic interventions as first event was observed in males (66.7% vs 52.8%), the proportion of type A dissections was similar between both sexes (26.7 vs 26.4%) with increased frequency of type B dissections in females as first aortic event (4.2 vs 15.3%) (p=0.026) Conclusions Male patients with MFS present higher aortic root diameters but similar BSA-indexed and zscores than females. Survival free of first aortic event or death is reduced in male with MFS, with greater frequency of elective aortic intervention. Although this last is driven by absolute aortic diameter, no increase on type A dissection was observed in women. These findings might suggest a potentially less aggressive manifestation of proximal aortic disease in women with MFS.Table:Comparison male and female Marfan

The aortic paradox: a nationwide analysis of 523,994 individual echocardiograms exploring aortic dissection

Abstract Background Increasing aortic dilation increases risk of aortic dissection. Nevertheless, dissection occurs below guideline-directed cut-offs for prophylactic surgery. There is no current large-scale population imaging data assessing aortic dimensions before dissection. Purpose To examine the proportion of aortic dissections occurring in people with aortic diameters below guidelines for prophylactic intervention. Methods Patients within the National Echo Database of Australia (NEDA) were stratified according to absolute, height-indexed and body surface area (BSA)-indexed aortic dimensions. Fatal thoracic aortic dissections (ICD-10-AM code I79) were identified via linkage with the National Death Index. Results 524,994 individuals were assessed, comprising patients with normal aortic dimensions (n=460,992), mild dilation (n=53,402), moderate dilation (n=10,029) and severe dilation (n=572). 274,992 (52.4%) were male, with median age 64 years and median follow-up time 6.9 years. 899 fatal aortic dissections occurred (normal diameter=610, mildly-dilated aorta=215, moderately-dilated =53 and severely-dilated=21). Using normal aortas as the reference population, odds of fatal dissection increased with aortic diameter (mild=OR 3.05, 95% confidence interval (CI) 2.61-3.56; moderate=OR 4.0, 95% CI 3.02-5.30; severe=OR 28.72, 95% CI 18.44-44.72). Due to the much larger number of patients without severe aortic dilation, 97.7% of fatal aortic dissections occurred in non-severely dilated aortas. Following sensitivity analysis, severe aortic dilation was responsible for at most 24.4% of fatal aortic dissections. Results were robust for absolute, height-indexed or BSA-indexed aortic measurements. Conclusion Although severe aortic dilatation is associated with a thirty-fold increase in fatal dissection, severely dilated aortas are implicated in only 2.3-24.4% of fatal dissections. This highlights the ‘aortic paradox’ and limitations of current guidelines. Future studies should seek to refine risk predictors in patients without severe aortic dilation.

Cardiac magnetic resonance (CMR) height-based allometric scaling in Southeast Asians; implications in the diagnosis and prognosis of left ventricular hypertrophy (LVH): the REMODEL study

Abstract Background Left ventricular hypertrophy (LVH) is a strong predictor of adverse cardiovascular outcomes (1). Although normalizing LV mass (LVM) to height exponents has been shown to reduce variability from body size, specific recommendations for height exponents are lacking due to the scarcity of normal cohorts to define appropriate height exponents (2). Cardiac magnetic resonance (CMR) is increasingly used in assessing LVM, and the existing body of research is based primarily on the MESA cohort (3). While the MESA cohort is ethnically diverse, the intrinsic effects of ethnicity may not fully be discerned if certain ethnic groups are under-represented. Purpose We aimed to demonstrate the diagnostic and prognostic implications of establishing height exponents specific to sex in a Southeast Asian cohort. Methods Non-overweight/obese Southeast Asian healthy volunteers (n=416) were used to establish appropriate height exponents and normal reference ranges of LVM. The impact of these height exponents was examined in a separate cohort of Southeast Asians with hypertension (n=878). All individuals underwent standardized cardiovascular magnetic resonance imaging (CMR). Primary outcome was a composite of acute coronary syndrome, heart failure hospitalization, stroke, and cardiovascular mortality. Cox regression analysis of various LVH measures were adjusted for 24-hour systolic blood pressure, diabetes, and hyperlipidemia. Results The height exponents for healthy females and males were 1.57 and 2.33, respectively. In patients with hypertension, sex-specific height exponents significantly increased the detection of LVH compared with body surface area (BSA) indexing (47% [n=409/878] versus 27% [n= 236/878], p<0.001). Most individuals re-classified to LVH with sex-specific height exponents were overweight (33.1%, n=58/175) or obese (64.6%, n=113/175). There were 37 primary events over 60 [37-73] months of follow-up. Regardless of indexing method, LVH was independently associated with increased adverse events (sex-specific height exponent hazard ratio (HR): 2.8 [1.25-6.29], P=0.013). The prediction ability of LVH diagnosis by sex-specific height exponents was similar to BSA indexing (HR: 5.43 [2.49-11.8], P<0.001). Conclusions Reference ranges specific to the ethnicity, sex and imaging modality are necessary to establish appropriate height exponents. Although utilizing sex-specific height exponents to index LVM resulted in significantly more LVH reclassification when compared with BSA indexing, this did not translate to a notable improvement in event prediction. Further research into alternative methods of LVM indexing is warranted.Abstract SummaryPredictive Ability of LVH Measures

Left atrial appendage volume estimated by artificial intelligence predicts atrial fibrillation recurrence after cryobaloon ablation

Abstract Background/Introduction The volume of the left atrial appendage (LAA), as measured in contrast-enhanced cardiac computed tomography (CCTA), has been previously reported as a predictor of long-term recurrence of atrial fibrillation (AF) following cryoballoon ablation procedures. Unfortunately manual assessment of LAA volume, is tedious and time-consuming, making it impractical for clinical practice. The recent advent of artificial intelligence (AI)-based methods offers a potential solution to this limitation. Purpose This study aims to evaluate the utility of LAA volume, as automatically measured by a state-of-the-art AI model for the fully automatic segmentation of LAA in CCTA, in predicting AF recurrence following cryoballoon ablation procedures. Methods We retrospectively analyzed a cohort of patients who underwent cryoballoon ablation for pulmonary vein isolation at our facility between 2010 and 2016. AF recurrence was determined through in-person visits and Holter monitoring at 3, 6, and 12 months post-ablation, followed by annual visits. The first three months post-ablation were considered a blanking period. An open-source deep neural network AI model [1] was utilized to perform automatic segmentation and calculation of LAA and left atrium (LA) volumes in. Receiver-operating characteristic curves were used to obtain optimal cut-off values for increased LAA and LA volumes. We then assessed the association of increased LAA and LA volume, and the LAA to LA volume ratio with recurrence-free survival using the Cox regression model. Results The cohort consisted of 212 patients (median age 62, inter-quartile range [IQR]: 55–65), with 25% having persistent AF before the procedure. Subjects were observed for a median period of 12 months (IQR: 12–36), with 70 of them (33%) experiencing a documented recurrent AF episode. The optimal thresholds for predicting AF recurrence were established as 9.8ml for LAA volume, 124ml for LA volume, and 0.086 for the LAA to LA volume ratio, respectively. An increased LAA volume demonstrated the strongest association with AF recurrence (hazard ratio [HR]: 2.6, 95% confidence interval [CI]: 1.55–4.2), followed by an increased LA volume (HR: 2.1, 95% CI: 1.3–3.4), persistence of AF (HR: 2, 95% CI: 1.2–3.3), and increased LAA to LA volume ratio (HR: 1.9, 95% CI: 1.1–3). Kaplan-Meier plots illustrating AF-free survival, are presented in Figure 1. After adjusting for age, persistent AF, left ventricular ejection fraction, and body surface area, all AI measurements remained significantly associated with a higher AF recurrence (Table 1). Conclusions Increased LAA volume, as assessed automatically by AI in CCTA, is a useful predictor of AF recurrence after catheter ablation for atrial fibrillation. The use of freely available, AI-assisted analysis of CCTA could be instrumental in assessing LAA volume, among other predictors, for long-term ablation success.Figure 1.

C-Reactive Protein-to-Serum Chloride Ratio: A Novel Marker of All-Cause Mortality in Maintenance Haemodialysis Patients

Background and Objectives: hypochloremia is an emerging risk factor for mortality in patients with chronic kidney disease. The pathophysiological mechanisms of this finding are not very clear. Some studies suggest the influence of inflammation as a synergistic factor, so we set out to analyse the association of a novel C-reactive protein-to-serum chloride ratio (CRP/Cl−) with the prognosis of maintenance haemodialysis patients and to assess its relationship with fluid status and body composition measured by bioimpedance. Materials and Methods: the present work is a retrospective cohort study of maintenance haemodialysis patients from our chronic outpatient haemodialysis programme between 1 January 2022 and 31 December 2022. (n = 281). Survival time was collected for all patients and analysed using the Kaplan–Meier method. A Cox proportional hazards regression model was used to evaluate survival probabilities. Variables included in the model were selected using a stepwise selection procedure based on the corrected Akaike information criterion (AICc), which balances model fit and complexity. Results: during a median follow-up of 306 days, 34 patients died. Patients in the fourth quartile of the CRP/Cl− (>0.118 mg/mEq) had higher overall mortality (log-rank test, p = 0.0011). In the Cox multivariate analysis, the variables significantly associated with higher mortality were higher modified Charlson index (MCI), lower body surface area (BSA), lower interdialytic weight gain (IDWG), and higher CRP/Cl− ratio. The latter variable was independently associated with higher overall mortality (adjusted hazard ratio = 1.027; 95% confidence interval [CI], 1.000–1.055 p = 0.0469). Conclusions: Higher CRP/Cl− ratio values were associated with higher all-cause mortality in our maintenance haemodialysis patients.

Cardiac morphology and function in patients with primary biliary cholangitis (PBC) without cirrhosis

Abstract Background Primary biliary cholangitis (PBC) is a chronic, autoimmune liver disease causing destruction of the small intralobular bile ducts in the liver. PBC patients can also develop extrahepatic manifestations. Though patients with PBC have often elevated levels of serum lipids, data concerning cardiac involvement is inconsistent and cardiovascular changes may be underdiagnosed. Purpose The purpose of the study was to assess cardiac morphology and function in patients with PBC without cirrhosis and comparison with control subjects. Methods We studied 52 females with PBC, and included in the analysis 22 females without cirrhosis, who were compared to 44 healthy female controls matched for age (53.4 ± 9.2 and 51 ± 8.3 yrs., respectively, p =0.312). Transthoracic echocardiography (TTE) was performed with the analysis of the left ventricular (LV) global longitudinal strain (GLS) and myocardial work. Additionally, impedance cardiography was conducted, with the analysis of the autonomic function using BRS (baroreceptor sensitivity), HRV (heart rate variability) and BPV (blood pressure variability). Results Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) differed between PBC and control group (128 ± 17 mmHg vs. 116 ± 11 mmHg, p=0.007 and 78± 12 mmHg vs. 75 ± 8 mmHg, p=0.024, and 73.5 ± 12 bpm vs. 71 ± 8 bpm , p=0.024, respectively). PBC group had larger diameter of the cardiac chambers when adjusted for body surface area (BSA), including left atrium (LA/BSA) and right ventricle (RV/BSA), as well as left ventricular mass (LWMI) and relative wall thickness (RWT), with no difference in the left ventricular end diastolic diameter (LVEDD/BSA). LV ejection fraction (EF) measured by bi-plane Simpson method was higher in PBC group. LV diastolic function parameters (E/A, E/e’) differed in patients with PBC when compared with controls, however, without signs of diastolic dysfunction. LV GLS indices (GLSAVG, GLSLAX, GLS4C, GLS2C) were significantly higher in PBC group, as well as global myocardial work indexes: global myocardial work (GWI) and global constructive work (GCW). Non-invasive autonomic assessment showed lower BPV in patients with PBC without cirrhosis, but no differences in baroreceptor sensitivity and HRV. Impedance cardiography did not show differences between both groups. Conclusion Our study shows that PBC patients without cirrhosis are characterized by remodeling and functional changes of the heart, when compared to age-matched controls. These changes could imply hyperkinetic circulation even before the development of cirrhosis in PBC patients.

A novel device for electrocardiographic imaging

Abstract Background Electrocardiographic imaging (ECGi) is a non-invasive imaging tool that allows 3D visualization and characterization of the electrical activity of the heart from measurements on the body surface by solving the so called "inverse problem of electrocardiography". This method helps overcome the limitations of the conventional12-lead ECG in diagnosing and locating heart arrythmias. We developed a textile 34-electrode imageless device (with no need for MRI or CT-scan). Purpose We aim to evaluate the feasibility and safety of the use of a novel textile imageless 34-electrode device for recording ECGi for identification of electrical activity of the heart. Methods and results The performance of a prototype data acquisition system (DAS) was evaluated in 158 individuals. Tests were conducted in three hospitals. The mean age was 43.32 years old (±17.44); mean height 167.31cm (±18.33); mean weight 70kg (±15.68). Almost 88% of the patients were in sinus rhythm. The relative frequencies of the targeted pathologies are listed in Figure 1. The collection of cardiac signals and posterior representation in virtual reality of a stereoscopic, holographic 3D-360º map, was achieved in 100% of the patients. Figure 2 shows the textile hardware with the silver dry electrodes and a screenshot of the software with an example of a voltage map in a patient in sinus rhythm. There were no adverse effects reported. The DAS is composed of 34 electrodes, being their distribution representative of the electrical activity on the torso. Several studies have discussed the minimum number of electrodes on the torso of the patient required to characterize the heart potentials from the electrical potentials on the torso surface through the inverse problem (1,2). We highlight that the representativeness condition of the electrical activity on the torso is crucial to appropriately estimate cardiac activity with the minimum number of leads on the DAS. Conclusion The use of a novel textile imageless 34-electrode device for recording ECGi for identification of electrical activity of the heart is feasible and safe.Targeted rhythmHardware and software

The edge artifact extraction method for Si3N4 ceramic bearing rolling element microcracks characterization

Aiming at the problem that the edge artifacts of Si3N4 ceramic bearing rolling element microcracks have low contrast, contain noise, and easily merge with the background, making it difficult to segment. A method based on 2D discrete wavelet transform and Otsu threshold segmentation is designed to achieve the extraction of microcrack edge artifact features. Wavelet decomposition is used to remove noise, while wavelet reconstruction features are used to restore lost details. Creation of 2D discrete wavelet transform functional equations combining wavelet reconstruction and wavelet decomposition to improve contrast and eliminate noise in images featuring edge artifacts. For the problem of feature edge artifacts that are difficult to remove, the threshold segmentation function equation is designed to maximize the interclass variance, and the optimal threshold value is selected to remove the edge artifacts. The experimental results show that the average PSNR of the Si3N4 ceramic bearing rolling body point, line, and surface microcrack edge artifact feature images enhanced by the method in this paper is close to 62.69 dB, and the average SSIM is about 0.77. The method in this paper improves the contrast of microcrack edge artifact features of Si3N4 ceramic bearing rolling bodies and makes the feature extraction effect of point, line, and surface microcrack edge artifacts more complete.

Sex differences in outcomes among patients undergoing transcatheter atrial septal defect closure: Do they benefit equally?

Abstract Background Although sex differences in congenital heart disease are prevalent and relevant, there is limited research on their role in atrial septal defect (ASD) closure. We aimed to investigate sex differences in baseline characteristics, procedural and long-term outcomes of patients with transcatheter ASD closure. Methods Data from adult patients undergoing ASD closure between 2005-2016 were retrospectively analyzed. Results Of the 853 patients included, 281 (32.9%) were male and 572 (67.1%) were female. Females were more symptomatic at presentation than males (p < 0.001). Males had a higher frequency of cardiovascular comorbidities than females (p < 0.001). Although echocardiographic right ventricular (RV) diameter relative to body surface area was equal in males and females (2.49 cm/m2 versus 2.57 cm/m2; p = 0.072), males had more RV dysfunction (12.1% versus 7.6%; p = 0.028). In contrast, females had higher RV systolic pressures (39.71 mmHg versus 37.23 mmHg; p = 0.025), and were more likely to have moderate to severe tricuspid regurgitation (15.4% versus 8.9%; p = 0.007). Males had larger defects with use of larger implants (p < 0.05). Procedure-related complications were rare and did not differ by sex. At 12-month follow-up, both male and females showed comparable decreases in RV diameter (-0.57 cm versus -0.59 cm; p = 0.751), RV systolic pressure (-4.57 mmHg versus -6.31 mmHg; p = 0.094), and severity of tricuspid regurgitation (p = 0.173; Figure). After a mean follow-up of 3 years (SD = 5), no significant differences were observed in the incidence of death (incidence rate ratio (IRR) = 0.49 [95% CI 0.27-0.83]; p = 0.402), new onset atrial fibrillation (IRR = 3.22 [95% CI 2.57-3.99]; 0.063), cardioversion or ablation (IRR = 0.40 [95% CI 0.20-0.71], p = 0.335), stroke/TIA (IRR = 0.29 [95% CI 0.12-0.56]; p = 0.745), and pacemaker implantation (IRR = 0.29 [95% CI 0.12-0.57], p = 0.728). Conclusions Although patient profiles differed by sex, procedural and long-term outcomes were comparable, suggesting that transcatheter ASD closure can be safely performed in both males and females.Figure.Sankey Plot

Left ventricular volume as a predictor of exercise capacity and functional independence in individuals with preserved ejection fraction

Abstract Background Cardiorespiratory fitness (CRF) is vital for independent living and is a powerful prognostic marker. Increased left ventricular (LV) volume has been linked with high CRF in athletes, but its utility as a diagnostic marker of low CRF across the entire health-disease continuum has yet to be tested. Methods This multi-center international cohort from Australia and Belgium examined the relationship between ventricular size on resting echocardiography and CRF (peakVO2 from cardiopulmonary exercise testing [CPET] or CPET with simultaneous echocardiography) in individuals with preserved LV ejection fraction (≥50%). LV end-diastolic volume (LVEDV) and LVEDV indexed to body surface area (LVEDVi) were tested as predictors of very low CRF (CRF associated with functional disability - peakVO2 < 1100ml or <18 ml/kg/min) and compared against other candidate measures of systolic and diastolic cardiac function that have been associated with heart disease. Thresholds for absolute and indexed LVEDV which best distinguished between lower and higher CRF status were identified. Results 2876 individuals (251 healthy non-athletes, 309 elite endurance athletes, 1969 individuals with unexplained dyspnea, 347 individuals with heart failure with preserved ejection fraction) were included. For the entire cohort, LVEDV had the strongest univariate association with peakVO2 (R2 = 0.45, standardized [std] β 0.67, p< 0.001) and, remained the strongest independent predictor of peakVO2 after adjusting for age, sex and body mass index (std β 0.44, p < 0.001). The relationship between LVEDV and VO2peak differed based on health/disease status (Figure 1). LVEDV demonstrated the greatest diagnostic capability in identifying functional disability (LVEDV AUC 0.72; LVEDVi AUC 0.71, Figure 2), outperforming ejection fraction, diastolic velocities, atrial volumes and pulmonary artery pressure estimates. The probability of achieving a peak VO2 below the threshold required for functional independence was highest for smaller ventricular volumes with LVEDV and LVEDVi of 88ml and 57 ml/m2 proving the optimal cut-points, respectively. Conclusions A small LVEDV is associated with a higher probability of poor exercise capacity, failure to achieve the peak VO2 required for functional independence and is the strongest independent echocardiographic predictor of CRF across the health-disease continuum.Figure 1.Ventricular Size and CRFFigure 2.Predictors of CRF status

Small heart size and premature death in 366,484 individuals with normal ejection fraction

Abstract Background In patients with preserved left ventricular ejection fraction (LVEF), small ventricular size has been associated with reduced functional capacity, but its impact on clinical outcomes is unclear. Purpose The goal of this study was to determine the relationship between small heart size and premature mortality within a large multi-centre adult patient cohort with transthoracic echocardiographic examinations. Methods We divided 366,484 individuals with LVEF ≥ 50% (including a sub-set of 279,442 individuals with high-normal LVEF ≥ 60%) by sex and increasing quartiles for LV end-diastolic volume (LVEDV), LVEDV indexed to body surface area (LVEDVi) and LV end-diastolic diameter to assess associations with 5-year mortality through linkage with the National Death Index. Results During 2-million person-years of follow-up, 65,241 deaths occurred. Increasing LV chamber size was associated with reduced odds of 5-year all-cause mortality, particularly for higher LVEF. As compared with the larger quartiles, the smallest cardiac size quartiles were associated with higher 5-year all-cause mortality, even after adjusting for age (Figure 1). The smallest LVEDVi quartile was associated with a 14% and 18% higher odds of 5-year all-cause mortality for males and females, respectively, with a greater effect with high-normal LVEF. For cardiovascular-related mortality, females in the smallest quartile for LVEDVi had a 17% increased odds of mortality, which increased to 30% in those with LVEF was ≥ 60%. In men, there was no significant association between smallest cardiac size and cardiovascular-related mortality. Conclusions In individuals with normal LVEF, small ventricular size is associated with increased mortality, particularly among females and those with higher LVEF.

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.

Cardiac chamber three-dimensional volumes and deformation predict clinical outcomes in chronic mitral regurgitation

Abstract Background In patients with mitral regurgitation (MR), cardiac remodeling assessed by two-dimensional (2D) echocardiographic linear indexes is highly variable and not suitable for individualized risk assessment. Purpose To evaluate whether measurements of myocardial strain and left atrial (LA), left ventricular (LV) and right ventricular (RV) three-dimensional (3D) volumes improve risk assessment in MR. Methods In the prospective 3D Echocardiography and Cardiovascular Prognosis in Mitral Regurgitation study (3D-PRIME), 176 patients with significant (moderate or greater) MR were investigated with 2D/3D echocardiography. Referral criteria for mitral intervention followed current guidelines. LA remodeling was assessed by the maximum and minimum 3D LA volume (3D-LAV), peak reservoir strain (LASr), and stiffness (i.e. the ratio: mitral peak E-wave divided by the annular e’ velocity (E/e´) / LASr). LV and RV were considered dilated in case of increased 3D end-diastolic (LV>=86/74 and RV>=87/74ml/m2 in men/women) and end-systolic volumes indexed for body surface area (LV>=41/33 and RV>=44/36ml/m2 in men/women). Peak global longitudinal strain was measured in the LV (LV-GLS) and the RV free wall (RV-FWS). The primary outcome was a composite of mitral valve surgery, percutaneous mitral edge-to-edge repair and death. Results During a 14 [8-24] months follow-up, the patients (70±13 years, 39% women) experienced 73 events including 14 deaths. In univariate survival analyses, LV and RV dilatation, but not LV-GLS and RV-FWS, were associated with the primary outcome (Figure) and had superior predictive value to 2D volumes and diameters (p<0.05). On contrary, both atrial size and function predicted outcome, with 3D-LAV (HR 1.01, 95% CI 1.00-1.01), LASr (HR 1.03, 95% CI 1.01-1.06) and increased LA stiffness (Figure) all significant predictors of events (p<0.05). In multivariate Cox analysis with adjustment for age, sex, body mass index and MR etiology, dilated LV (HR 2.6, 95% CI 1.5-4.4), dilated RV (HR 2.0, 95% CI 1.1-3.6) and increased LA stiffness ((HR 2.4, 95% CI 1.3-4.6) were independently associated with higher rate of events (p<0.05). Conclusion In patients with moderate or greater MR, increased cardiac chamber 3D volumes and LA stiffness, as well as impaired LA reservoir strain are associated with higher risk of disease progression towards mitral valve intervention and death. Our findings indicate that assessment of both cardiac chamber 3D size and LA deformation can contribute to increased diagnostic and prognostic precision in patients with MR.

Impact of epicardial adipose tissue and atrial functional impairment in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement

Abstract Background Recent studies outlined the additional prognostic value of atrial function in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). At the same time, increased epicardial adipose tissue (EAT) volumes have proven impact on atrial functional impairment in cardiovascular disease by nurturing adverse atrial remodelling. Purpose To explore the impact of increased EAT volumes as a potential pathomechanistic factor of atrial functional impairment in patients with severe AS undergoing TAVR. Methods 146 patients with severe AS underwent cardiac magnetic resonance (CMR) within 48h prior to TAVR between January 2017 and June 2021. Image analyses included myocardial volume quantification as well as CMR-feature-tracking derived strain. EAT volumes were manually delineated on short axis stacks in end-diastolic cardiac phases and indexed to body surface area. Functional and morphological parameters were compared between patients with high and low EAT volumes. Associations between morphological and functional parameters and EAT were tested using a multivariable linear regression model including patient specific parameters. Results After dichotomization at the median of 46.5ml/m2 total EAT volume, patients were assigned to high- and low-EAT groups accordingly. There was comparable age and body mass index and similar rates of co-morbidities such as hypertension, diabetes and atrial fibrillation in both groups. We observed a higher number of male patients in the high-EAT group (36 [53%] vs. 50 [72%], p=0.018). Regarding left and right ventricular dimensions and function, no differences could be shown. Left atrial (LA) end-systolic volumes were significantly higher in the high-EAT group (29.4ml/ml² [19.7-39.4] vs. 40.9ml/ml² [30.2-59.3], p=0.008), while there were no significant differences in end-diastolic volumes. Furthermore, LA reservoir strain was significantly lower in the high-EAT group compared to the low-EAT group (18.0% [11.7-21.0] vs. 11.8% [7.7-16.4], p=0.008) and was independently associated with higher EAT volumes (p=0.018) irrespective of cardiovascular risk factors and left ventricular (LV) systolic function in a multivariable regression model. Conclusion In patients with severe AS undergoing TAVR, increased EAT volumes are associated with both, morphological and functional changes of the atria. As impaired atrial function was previously shown to be an important predictor of mortality in TAVR patients, those results potentially render EAT as an additional pathomechanistic link between atrial remodelling and worse outcome in TAVR patients.

Effect of empagliflozin on epicardial adipose tissue volume in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF)

Abstract Background Epicardial adipose tissue (EAT) is postulated to be linked to the pathophysiology of heart failure with reduced ejection fraction (HFrEF), acting both as a biomarker and a potential therapeutic target. Investigating changes in EAT volume following treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitor could provide valuable mechanistic insights. Purpose This posthoc substudy of the SUGAR-DM-HF trial aimed to assess the effect of the SGLT2 inhibitor empagliflozin on EAT volume. Methods Within a multicentre, randomised, double-blind, placebo-controlled trial, the effects of empagliflozin were evaluated in patients with HFrEF (New York Heart Association functional class II-IV, left ventricular ejection fraction (LVEF) ≤40%), and type 2 diabetes or prediabetes. Patients with atrial fibrillation/flutter were excluded to avoid image degradation. Patients were randomly assigned 1:1 to empagliflozin 10mg daily or placebo. EAT volume was quantified using cardiovascular magnetic resonance (CMR) cine imaging at baseline and week 36, and reported as: (a) total EAT volume (mL); (b) EAT volume indexed to body surface area (mL/m2); (c) % change from baseline. Observers were blinded to subject identification, scan date, clinical data, and randomization arm. Scans with major artefacts were not analysed. Results One hundred five patients were randomly assigned: mean age 68.7 (SD, 11.1) years, 77 (73.3%) male, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LVEF 32.5% (9.8%). Baseline EAT volume was available in 101 patients (median [IQR] 85 [67-104] mL and 41 [34-52] mL/m2). Paired baseline and 36-week EAT volume was available in 90 patients. Higher baseline total EAT volume was associated with male gender, higher body mass index, coronary artery disease, elevated serum creatinine, higher left ventricular end-diastolic volume, and higher left ventricular mass (TABLE). EAT volume changed by -2.7 mL / -1.3 mL/m2 / -3.1% in the empagliflozin group versus 0.3 mL / 0.3 mL/m2 / 1.5% in the placebo group (between-group difference -3.4 mL, 95% CI -6.7 to -0.1; p=0.045 and -1.7 mL/m2, 95% CI -3.4 to -0.04; p=0.045) at 36 weeks (FIGURE). The beneficial reduction in left ventricular end-systolic volume indexed to body surface area observed with empagliflozin treatment was not modified by baseline total or indexed EAT volumes (p interaction=0.31 and 0.45, respectively). Conclusion Empagliflozin treatment significantly reduced EAT volume. This may represent an additional benefit of SGLT2 inhibition in HFrEF.

Structural echocardiographic parameters in male and female Asian athletes: a systematic review and meta-analysis

Abstract Introduction Following repetitive structured and intense physical training, elite athletes’ hearts undergo physiological cardiac remodelling, including increased left ventricular (LV) size and LV wall thickness. These changes may mimic those seen in pathological cardiac conditions such as dilated and hypertrophic cardiomyopathy, posing a challenge for accurate diagnosis. Reference ranges for common echocardiographic parameters in elite Caucasian and Black athletes have been reported, facilitating differentiation between physiological and pathological changes in these demographics. However, there remains a paucity of data for Asian athletes despite their increasing representation in global sport. Methods We searched MEDLINE via PubMed, Embase, and the Cochrane Database for relevant studies from inception till 20th November 2023. We included observational studies that reported relevant echocardiographic parameters in elite Asian athletes. Studies that did not report gender-specific cardiac imaging parameters were excluded. After study selection and data extraction, random-effects meta-analysis of means was performed to obtain the weighted mean and 95% confidence intervals (CI) of common echocardiographic parameters stratified by gender. Results Our final search yielded 10 studies comprising a total of 1,111 elite athletes (996 male, 115 female; 53% Japanese, 21% uncategorised, 14% South-East Asian). Athletes participating in skill and power disciplines were excluded from analysis post-hoc due to a paucity of data and extreme data ranges. In male athletes, mean LV wall thickness was 9.4 mm (95% CI 8.5-10.3, I2 = 98.9%), mean LV end diastolic diameter was 54.7 mm (95% CI 52.5-57.0, I2 = 98.6%), mean LV mass indexed to body surface area was 97.5 g/m2 (95% CI 90.5-104.5, I2 = 97.5%) and mean aortic root diameter was 31.9 mm (95% CI 29.2-34.7, I2 = 99.5%). In female athletes, mean LV wall thickness was 7.9 mm (95% CI 7.5-8.4, I2 = 85.4%), mean LV end diastolic diameter was 47.1 mm (95% CI 45.8-48.3, I2 = 77.3%), mean LV mass indexed to body surface area was 79.5 g/m2 (95% CI 69.2-89.7, I2 = 92.8%) and mean aortic root diameter was 27.5 mm (95% CI 26.9-28.1). Conclusion This meta-analysis describes commonly reported echocardiographic parameters in elite Asian athletes from endurance and mixed sport disciplines. The absolute values of all reported parameters appear to fall far below reported limits for non-Asian athletes, highlighting substantial ethnic and regional variation in cardiac remodelling in elite athletes. While our results facilitate preliminary referencing of expected normal ranges in this demographic group, further studies are necessary to fully define the cardiac characteristics of Asian athletes.

The correlation between cardiac magnetic resonance imaging and echocardiography in patients with severe ischaemic cardiomyopathy

Abstract Background Left ventricular ejection fraction is the single metric that guides therapeutic decision-making, risk stratification and prognosis in patients with severely impaired systolic function. Although cardiac magnetic resonance imaging (CMR) is the current reference standard for quantification of ventricular volume and function, echocardiography is used more often as it is more widely available and less expensive.(1) Aims To evaluate the correlation between CMR and echocardiography in quantifying left ventricular (LV) volume and function and to determine whether these measurements are associated with clinical outcomes in patients with severe ischemic cardiomyopathy (ICM). Methods Participants recruited to the REVIVED-BCIS2 trial who had undergone baseline CMR or echocardiography were included in this analysis. All scans were analyzed in blinded core laboratories as previously reported.(2,3) All volumes were indexed to body surface area. Spearman correlation, Bland Altman analysis and coverage probability methods were performed to assess the correlation between the two modalities. A Cox proportional hazards model was used to assess the association between imaging metrics and the primary outcome, a composite of all-cause death and aborted sudden death. A sensitivity analysis was conducted a priori, restricted to patients undergoing both scans within 60 days of each other. Results A total of 373 participants with paired imaging data were included: mean age 69±9 years, 87% male, BMI 28±5. A moderate correlation was detected for volume measurements between the modalities (end diastolic volume index (EDVI) r=0.66 end systolic volume index (ESVI) r=0.68), with a weaker correlation for LV ejection fraction (EF) (r=0.41). Bland-Altman plots showed moderate agreement in LVEF measurements (Table 1). The sensitivity analysis included 199 patients, and showed similar results (EDVI r=0.72, ESVI r=0.73 LVEF r=0.43, all p<0.000). Only 7.5% of the paired LVEF measurements were within 5% of each other. 30% of participants were misclassified by echocardiography as having an LVEF>35%. (Figure 1) CMR ESVI was associated with the occurrence of the primary outcome (HR 1.05 per 10ml increment, 95% CI 1.00-1.10) however echo ESVI (HR 1.05 per 10ml increment 95% CI 0.99 – 1.10) and all other imaging metrics were not. Conclusion Left ventricular volumes and ejection fraction on CMR and echocardiography were only modestly correlated in this population with severe ICM. When using the binary EF threshold of 35% that is commonly used to select patients of implantable defibrillator therapy, almost a third of patients at risk would have been missed by echocardiography alone. The additional insights provided by CMR, including scar burden, further support preferential use of this modality in the assessment such patients.

Diagnostic value of low dose dobutamine stress echocardiography in paradoxical low flow low gradient aortic stenosis

Abstract Background In aortic stenosis with low-gradient scenarios distinguishing between fixed and pseudo-severe stenosis becomes challenging. Low-dose dobutamine stress echocardiography (DSE) is recommended for classical low-flow low- gradient stenosis with reduced ejection fraction. Doubts of DSE's utility in paradoxical low-flow low-gradient (PLFLG) stenosis when ejection fraction is preserved are partially reasoned by proposed inefficiency in generating a contractile reserve 1. Guidelines advocate an integrated approach, combining various clinical and imaging aspects 2. Purpose This study aimed to investigate usefulness of DSE in PLFLG stenosis, identifying specific features to predict the possibility of generating significant stroke volume augmentation and distinguishing fixed aortic stenosis. Methods We identified patients with aortic stenosis who underwent DSE and multi-modality imaging at our centre between 2020 and 2023. Among them, those with PLFLG situations were used for detailed analysis. Multiple linear regression analysis was performed to identify parameters predictive of significant contractile reserve, defined as 20% stroke volume increase from baseline. For patients demonstrating contractile reserve we assessed predefined parameters by receiver operating characteristics (ROC) analysis to predict fixed stenosis defined as final aortic valve area < 1cm² and valve area change <0.2cm² or final mean pressure gradient >40mmHg. For predictive value of Agatston score we conducted post-hoc analysis. Results Among 256 DSE cases, 67 were conducted for PLFLG stenosis. Patients were 82 years of median age and mostly female (63%). Symptoms included dyspnea in 90% and angina in 40% of cases. Baseline echo showed median aortic valve area (indexed to body surface area) of 0.8cm² (0.44cm²/m²) with mean pressure gradient of 20mmHg. Contractile reserve was inducible in 70% of patients, of which 74% showed criteria of fixed stenosis. Higher left ventricular end-diastolic diameter (LVESD) and lower baseline systolic flow-rate were predictive for contractile reserve (p<0.05). Among patients with contractile reserve ROC for baseline mean pressure gradient, acceleration time (median 0.08s; range 0.04-0.11s) and acceleration time to ejection time index (0.28; range: 0.148-0.458) revealed good prediction of fixed stenosis in DSE meanwhile Agatston calcium score (median 1076; range: 301-8821) did not (figure 1). No correlation was found between Agatston score probability of severe stenosis and aortic valve pressure gradient behavior with increased stroke volume (figure 2). Conclusion DSE proves to be a useful a method in the differentiation between fixed and pseudo-severe stenosis in PLFLG situation. Our findings question the predictive value of Agatston score for aortic valve behavior with increase of stroke volume and warrant further investigations regarding value of acceleration time and acceleration time to ejection time index in those patients.Receiver operating characteristicsPost-hoc analysis of Agatston score

Association of non-invasive assessed anatomical features with functional testing in coronary artery anomalies - NARCO trial

Abstract Introduction Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital condition believed to carry an increased risk for myocardial ischemia. However, correlation between anatomical characteristics and ischemia remains unclear. Therefore, this study aimed to assess: 1. The difference of invasive fractional flow reserve (FFR) and intravascular ultrasound (IVUS)-based minimal lumen area (MLA) between baseline and stress. 2. The association of coronary computed tomography angiography (CCTA)-based anatomical characteristics to invasively measured hemodynamics and IVUS in AAOCA. Methods Consecutive patients with AAOCA and presence of ≥1 anatomical high-risk features (i.e. intramural course (IM), slit-like ostium, acute take-off angle or proximal narrowing), were systematically evaluated as part of the NARCO trial using CCTA, FFR using adenosine (140 µg/kg/min), dobutamine-volume stress (20-40mcg/kg/min, 0.5-1mg atropine and 3L of saline solution) and IVUS- MLA of IM. Anatomic high-risk features were quantified by CCTA including ostial lumen area and IM-MLA, IM-width, IM-height, IM-elliptic ratio, take-off angle, proximal narrowing and IM length of the anomalous coronary segment. Results A total of 94 patients with AAOCA were screened, whereas 48 showed high-risk anatomic features and underwent the complete stress protocol. Mean age was 54±12 years and 36 (75%) were male and 39 (81%) presented with symptoms. FFRstress was significantly lower than FFRadenosine (0.88 [0.81-0.91] vs. 0.91 [0.87-0.94], p<0.001) (Figure 1). FFRadenosine was ≤0.8 in 5 patients (10%), and FFRdobutamine was ≤0.8 in 12 patients (25%), resulting in 7 (15%) with FFRadenosine >0.8 while FFRdobutamine was ≤0.8. IVUS-MLA was decreased from 6.3 (5.4-8.2) mm2 to 5.4 (4.2-7.1) mm2 during stress (p<0.001) (Figure 2), while elliptic ratio increased from 2.6 (2.1-3.4) to 3.3 (2.5-4.4) (p<0.001). Logistic regression analysis for body surface area adjusted CCTA derived high-risk features showed, that only ostial lumen area, IM-MLA, -elliptic ratio and -width could predict FFRstress ≤0.8. Receiver operating curve analysis showed that ostial width had the greatest AUC with 0.86 (accuracy 83%, sensitivity 83%, and specificity 83%). Eight out of 12 (67%) patients with hemodynamic relevance underwent surgery, 2 (17%) underwent stenting and 2 (17%) were treated with medication. Conclusion In patients with AAOCA and anatomic high-risk features, only one quarter are hemodynamic relevant. FFR during dobutamine-volume stress showed to be the more sensitive stress modality as compared to FFRadenosine. CCTA derived ostial and IM anatomical severity is associated with ischemia under stress. Comprehensive functional and anatomical assessment of AAOCA helps to optimize patient management and avoid unnecessary revascularization.Figure 1:FFRadenosine vs FFRstressFigure 2:IVUS-MLArest vs IVUS-MLAstress

Cardiovascular magnetic resonance to differentiate veteran athlete's heart with cavity dilatation and mild dilated cardiomyopathy

Abstract Introduction Endurance athletic training may lead to left ventricular (LV) dilatation and mildly reduced resting LV function which can be difficult to differentiate from dilated cardiomyopathy (DCM). Myocardial fibrosis is increasingly recognised in lifelong athletes and is also prevalent in DCM where it confers adverse prognosis.(1,2) However, it is unknown whether the pattern and prevalence of fibrosis in athletes with cavity dilatation differs from DCM. In this study, we compared the CMR fibrosis distribution and tissue characteristics between athletic LV dilatation and mild DCM patients. Methods We prospectively recruited 113 males; 64 endurance athletes and 49 mild DCM patients. Inclusion criteria Age 50-80 years, LVEF 45-54% and LV end-diastolic volume indexed to body surface area (LVEDVi)≥110ml/m2. Athletes trained≥10 weekly hrs for≥15 yrs. Exclusion criteria; Chest pain, prior coronary revascularisation, severe valvular disease, myocarditis, hypertrophic cardiomyopathy, inducible ischaemia or myocardial infarction on CMR. CMR protocol included volumetric assessment, T1 mapping, quantitative stress perfusion and quantitative late gadolinium enhancement. Statistical analysis between groups was performed using unpaired t-test and receiver-operator curve (ROC) analysis. Results LVEDVi was not significantly different between athletes and mild DCM patients (123.3±12.6 vs 129.8±23.1ml/m2, P=0.057). However, LVEF (52.0±6.1 vs 47.6±5.2%, P<0.001) and right ventricular (RV) EDVi (121.0±14.3 vs 97.6±25.2ml/m2, P<0.001) were both greater in athletes. There was no difference in non-ischaemic fibrosis prevalence between both groups (50.0 vs 49.0%, P=0.915) nor the burden of fibrosis (3.5±2.9 vs 7.4±12.0g, P=0.087). However, the distribution of fibrosis varied with a significantly greater prevalence of basal mid-myocardial inferolateral fibrosis amongst athletes (87.5 vs 50.0%, P=0.002) whereas basal mid-myocardial inferoseptal fibrosis was significantly more common in mild DCM (45.8 vs 9.4%, P=0.002). Native T1 (1249.0±38.1 vs 1308.3±47.1ms, P<0.001) and extracellular volume (ECV) (22.0±2.1 vs 25.9±3.5%, P<0.001) were both lower in athletes than mild DCM patients. Furthermore, athletes had higher myocardial perfusion reserve (MPR) (3.65±1.30 vs 2.76±0.92, P<0.001) and stress myocardial blood flow (MBF) (2.09±0.70 vs 1.62±0.66, P<0.001). On ROC analysis, native T1 (area under curve (AUC) 0.89, P<0.001), ECV (AUC 0.85, P<0.001) and stress MBF (AUC 0.68, P<0.001) were able to differentiate athletes and mild DCM. Native T1 and ECV were significantly better at discriminating than MPR (P<0.001). Conclusion Myocardial fibrosis was highly prevalent in both veteran endurance athlete's heart and mild DCM whilst its distribution was distinctive between the groups. Native T1 and ECV were the best discriminators. Recognition of fibrosis patterns and associated tissue characteristics may be clinically useful to differentiate these two overlapping phenotypes.Figure 1; LGE distribution in athletes cFigure 2; CMR tissue characteristics to