End-diastolic Volume Research Articles

Normal reference values of left atrioventricular coupling index on two-dimensional echocardiography

Abstract Background From a physiological background, there is close relationship between left atrial (LA) and left ventricular (LV) expressed as coupling. The assessment of LA/LV coupling may reflect LV dysfunction and differentiate between normal and abnormal LV function. Aim of study The study is designed to sample normal subjects to provide the normal reference values of LA/LV coupling index (LACI) according to age and sex using 2-dimensional echocardiography (2DE). Methods 550 healthy subjects (51.9±17.8 years, 56% males) were included with good 2DE image quality enabled measurement of end-diastolic volumes of both LA and LV. LACI was defined as the ratio between LA to LV end-diastolic volumes. Results An off-line analysis of apical 4-chamber and 2-chamber views to obtain the 2DE measurements was performed within short time (1.5± 0.3 min). Measurement of LACI was obtained in all individuals. Subjects were divided into 3 age groups (G I: 18-40 years, G II: 41-65 years, and GIII: >65 years). As shown in table 1, the normal LACI values in the whole population was 0.17±0.08 with significantly higher in females (0.178±0.09) than males (0.15±0.06); P<0.02. The LACI values tends to be higher in females than males in the subdivided 3 age groups but not statistically significant. In both sexes, increasing age was associated with significant reduction of the mean LVEDV (P<0.0001), significant increase of the mean LAEDV (P= 0.004), and significant increase of LACI (P< 0.0001); especially considering the differences between the youngest and oldest age groups. Conclusions Measurement of LACI is feasible and easily obtainable using 2DE. Age and sex should be considered when defining normal reference values for LACI. The standardization of normal LACI values will help the future studies to assess the changes of these normal values in various cardiac abnormalities for prognostic risk stratification.

Relation between wearable heart rate monitor derived training load and cardiac adaption in endurance athletes

Abstract Background No studies have effectively measured training load (TL) from wearable heart rate (HR) monitors and determined its relation to exercise induced left and right ventricular (LV, RV) remodeling. A better insight into drivers of exercise induced cardiac remodeling is of clinical relevance to guide training advice in athletes at risk of adverse remodeling. Purpose We determined the TL, based on HR monitoring by commercial wearables[1]. The number and duration of training sessions was quantified during a period of 3 months. Training-intensity was calculated as Edwards TRIMP (eTRIMP) based on the product of training duration in one of 5 HR zones (1=light, 5=very vigorous) and the coefficient related to the respective HR zone. Methods Training data was collected in 2 prospective multicenter studies. Master@Heart comprises endurance trained middle-aged men aged 45 to 70years[2]. Pro@Heart consists of elite athletes aged 16 to 23years[3]. For this analysis, all male athletes with complete training data recorded using a chest-worn HR monitor for 3 months were included. Using an in-house developed pipeline, maximal HR and TL were calculated from raw training data. Cardiac magnetic resonance imaging was performed to measure indexed LV/RV end-diastolic volume (LVEDVi, RVEDVi), end-systolic volume (LVESVi, RVESVi), ejection fraction (LVEF, RVEF) and LV mass (LVMi). Results Pro@Heart athletes (n=69; age 21.9 ± 4.2 years) trained more than Master@Heart athletes (n=82; age 55.2 ± 6.5 years) and their total 3-month TL (eTRIMP) was also higher (9718 ± 3190 vs. 5499 ± 3775min; P<0.05 and 22339 ± 7350 vs. 13438 ± 8880 AU; P< 0.05; Table 1). Considering all athletes, there was a strong correlation between both training duration and eTRIMP and LVEDVi, LVESVi, LVMi, RVEDVi and RVESVi. Training duration in zone 1&2 correlated well with LVEDVi, LVESVi, LVSV, LVMi, RVEDVi and RVESVi (Table 2). We found small significant negative correlations between duration and eTRIMP compared to LVEF and RVEF (Table 2). To filter out individual training factors influencing cardiac remodeling we used a partial least squares method which included time and percentage of time spent in training zones and age. Accordingly, training duration in zone 1&2 and age were the main predictors of cardiac volumes and LVMi. For LVEF, age and time in zone 3 was most predictive, whereas for RVEF zone 3 and to a lesser degree zone 1&2 were the main predictors, irrespective of age. Interestingly, time spent in high intensity zones 4 and 5 was not predictive. Conclusion We prospectively quantified TL in comparison to CMR-derived measures of cardiac remodeling and demonstrated that training duration in low intensity training zones is most predictive for cardiac volumes and mass, whereas LVEF and RVEF are more closely associated to time in zone 3. Very vigorous intensity exercise was not predictive, likely due to limited time training in zone 4 and 5.

Combined 3D left ventricular-arterial coupling and 3D left atrial-ventricular coupling indices could better predict MACE in young patients with STEMI

Abstract Background Left ventricular arterial coupling index (VAC) proved to be a key determinant of cardiovascular performance. Previous trials also emphasized the prognostic value of left atrial-ventricular coupling index (LACI) that was independently associated with cardiovascular death and all-cause mortality. Both indices have been associated with disease severity and adverse outcomes. Purpose We aimed to evaluate the prognostic role of 3D VAC, 3D LACI and their combination assessed by 3D echocardiography in a cohort of young patients with STEMI. Patients and methods In this prospective study we enrolled 76 young consecutive patients (under 50 years old) with STEMI treated by primary PCI who underwent both 2D and 3D echocardiography. 3D VAC was calculated as the ratio between arterial elastance (EA) and end-systolic left ventricular elastance (EES), based on a formula proposed by Chen. 3D LACI was determined as the ratio between 3D left atrial end-diastolic volume (minimal atrial volume) and 3D left ventricular end-diastolic volume. Patients were followed up for one year after STEMI and the primary endpoint was the occurrence of MACE defined as death from cardiovascular causes, heart failure requiring hospital admission, or repeat revascularisation. Results Out of 76 patients, 15.8% had an adverse event during the 12 months follow up period. We divided the patients in two groups according to the presence or absence of MACE. Patients with MACE had higher VAC (2.15±0.62 vs. 1.25±0.29%, p<0.0001) and higher LACI (25.1±7.17% vs. 18.3±6.58%, p=0.002). In ROC analysis VAC and LACI combined had the best AUC for MACE prediction (AUC 0.961, p<0.0001), followed by VAC (AUC 0.922, P<0.0001), and then, LACI (AUC 0.772, P<0.001). For each variable we determined a cut off value. A value over 1.7 for VAC and 23.83% for LACI can predict unfavourable outcome with 83.3% sensitivity and 97.1% specificity for VAC and 67% sensitivity and 80% specificity for LACI. In both univariate and multivariate COX regression analysis, both VAC and LACI remained independent predictors for MACE. Moreover, their combination proved to have better predictive value for adverse events compared to each taken separately. We divided the study population into 4 groups: Group 1: VAC < 1.7 and LACI < 23.83%. Group 2: VAC <1.7 and LACI > 23.83%. Group 3: VAC > 1.7 and LACI < 23.83% and Group 4: VAC > 1.7 and LACI >0.23.83%. Kaplan Meier analysis shows significant differences among groups (log rank χ2 = 35.48, p < 0.0001). Calculation of Kaplan-Meier curves for the four groups indicated that the combination of the VAC > 1.7 and LACI > 23.83% had the strongest predictive power for MACE. Conclusion In conclusion 3D VAC and 3D LACI combined are better at predicting adverse events than each variable taken separately and could be used for a more accurate risk stratification in young patients with STEMI.

Prospective assessment of risk factors for appropriate ICD intervention in patients with ischemic cardiomyopathy: results of PARCADIA trial

Abstract Background There is still a big unmet need for better risk stratification tools to identify patients at high risk for sudden cardiac death in the era of primary prevention ICD therapy. Scar burden on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging may be a risk marker for the prediction of ventricular arrhythmia in post-myocardial infarction (MI) patients. Purpose The aim of the PARCADIA trial was to assess whether scar characteristics, determined via LGE-CMR, or other baseline risk markers are associated with appropriate ICD therapy. Methods In this prospective, multi-center, clinical trial, we enrolled post-MI patients with an indication for de novo primary prevention ICD. Main exclusion criteria were indication for cardiac resynchronization therapy and NYHA class IV. Prior to the ICD implantation, LGE-CMR was performed to analyze the amount of scar tissue (LGE core mass + grey zone mass) and LV function / volumes. A 24h Holter recording was performed to collect information on potential triggers like premature ventricular beats (PVB) and sympathetic-vagal balance based on heart rate variability (HRV). Follow-ups were performed in-office every 6 months, including remote monitoring. Appropriate ICD therapy was used as primary endpoint and adjudicated by a clinical event committee. Results 199 patients were enrolled at 5 investigational sites in Europe. Patients mean age was 64.3 years, with a mean LVEF of 27.7 %, timing from the index MI was 9.1 years, and 42.7% received a primary PCI on index MI. After a median follow-up duration of 47.7 months, 23.1% of patients received appropriate ICD therapy. In 135 patients (67.8%), quality of LGE-CMR was sufficient for detailed analysis. The mean LGE core mass (20.5 vs. 19,7 g) and grey zone mass (10.5 vs. 11.4 g) was not different in patients with or without appropriate ICD therapy, also not when corrected for LV mass. However, LVEF (28.5 vs. 32.9 %) was lower, while diastolic myocardial mass (141 vs. 125 g), and end-diastolic volume (265.0 vs. 226.7 ml) were significantly higher in patients with appropriate ICD therapy. On 24h Holter the mean PVB burden (3695 vs. 1643 beats), and non-sustained ventricular tachycardia (12 vs. 0.9), were higher in patients with appropriate ICD therapy, while the HRV (96.1 vs. 113.1 SDNN) was lower. In univariate analysis the variables LVEF, timing to index MI, primary PCI on index MI, PVB burden and HRV appeared to be predictors for appropriate ICD intervention, while in multivariate analysis LVEF and PVB burden remained predictive. Conclusion In post-MI patients with appropriate ICD therapy, scar burden was not different from patients without appropriate ICD therapy. Only LVEF and PVB burden were independent predictors of increased arrhythmogenicity. Improved CMR analysis on scar characteristics (conduction channels) to identify potential arrhythmogenic regions might be the topic for future research.

Volume-pressure loop hemodynamic characterization of pulmonary hypertension

Abstract Background Pulmonary hypertension (PH) includes a wide spectrum of pathologies with different pathological bases and a variety of clinical scenarios in which right ventricular (RV)-pulmonary artery (PA) coupling has relevant prognostic implications. Currently, diagnosis and hemodynamic severity of PH is typically based on mean pulmonary arterial pressure (mPAP), pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR). However, this conception does not take into consideration the evolution of these parameters throughout the cardiac cycle. We hypothesized that not only the magnitude but also the dynamics over time plays an important role in RV adaptation to pressure overload (i.e., constant fixed resistances throughout the cycle will have a different impact than a fluctuating resistances). Purpose To assess PA hemodynamic patterns throughout the cardiac cycle and their association with RV remodelling, by combining right heart catheterization (RHC) and cardiac magnetic resonance imaging (CMR) data. Methods 66 patients with PH (38 women, aged 63.59±14.70years, BMI 28.49±6.21 kg.m2) who underwent RHC in the supine position with a 7.5-FrSwan-Ganz catheter under fluoroscopic guidance (37 precapillary, 17 combined pre-postcapillary, 12 isolated postcapillary PH) and CMR with flow-encoded phase-contrast sequence were included. Pressure and flow tracings at the level of the main PA were integrated to obtain volume-pressure loops throughout the cardiac cycle. The resulting patterns based on morphology (Image 1) and slope (Pattern 1 mean slope 16,11% vs Pattern 2 mean slope 10,37%) were analysed and classified into 2 groups: Pattern 1 and Pattern 2. RV end-systolic (iRVESV) and end-diastolic volumes (iRVEDV), RV ejection fraction, RV mass and presence of late gadolinium enhancement (LGE) at the RV insertion points were compared between groups using parametric and non-parametric tests. Results Patients with Pattern 1 showed significantly higher mPAP (46.03±11.62 vs. 35.77±8.10 mmHg) and iPVR (746.22±584.54 vs 319.56±306.21 dynes.s.cm-5.m2) and lower PCWP (11.8±7.6 vs 17.7±7.2 mmHg). Precapillary PH patients more frequently presented a Pattern 1 (n=27; 77.1% vs 10; 32.3%). In addition, patients with Pattern 1 had higher RV volumes (iRVEDV= 105.45±34.62 ml/m2 vs 84.22±35.0 ml/m2, p=0,002; iRVESV 65.05±27.59 ml/m2 vs 44.63±25.09 ml/m2, p=0,001), poorer RV function (RVEF 39.81±11.33% vs 48.96±10.90%; p=0,001), larger RV mass (27.95±9.46 vs 23,44±7.46 g/m2, p=0,045) and smaller left atrial size (24.18±11.47 vs 34.06±19.15 cm2, p<0,001) than patients with Pattern 2. The quantification of LGE was also higher in Pattern 1 as compared with Pattern 2 (5.4±2.4% vs 3.0±2.3%, p<0.001). Conclusion Volume-pressure loops at the level of the main PA may differentiate patterns of PA hemodynamic fluctuations that have different impact on RV performance regardless the PH severity within the wide spectrum of PH.Volume-pressure loop patterns

Fully automated artificial intelligence-based cine cardiac magnetic resonance image quantification

Abstract Background Analyzing cine cardiac magnetic resonance (CMR) images is a task that demands substantial experience and time, and it is subject to both inter- and intra-observer variability. Existing automated tools in the clinics for image analysis often necessitate substantial editing to enable accurate quantification. Objective To tackle this issue, in this study, we developed and validated a fully automated artificial intelligence (AI)-based system for the analysis of cine CMR images, aiming to address these challenges. Method In this study, 1,038 patients with CMR images were enrolled. Out of these, 350 CMR images, along with corresponding segmentations for the left ventricle myocardium (LVM) and the left- and right ventricles (LV and RV, respectively), sourced from open access data from 5 centers and databases (with different cardiac diseases), were utilized for model development. The remaining images from two local registries were used to evaluate the model. A 2D U-Net network with deep supervision, enhanced with various image augmentation techniques, was developed for automatic segmentation. The developed model was subsequently utilized to segment the test dataset of 4D (3D+time) short-axis cine CMR images. End-diastolic volumes (EDV) and end-systolic volumes (ESV) were automatically detected from these segmentations and evaluated against the ground truth calculations performed by two experienced physicians using commercially validated software. Results In the test set, Dice scores of 0.84, 0.90, and 0.93 were achieved for the RV, LV, and LVM, respectively. The mean percentage error for EDV was 0.6% for LV and -6.32% for RV. Regarding ESV, the mean percentage error was 2.95% for LV and -6.32% for RV. A -6.95% error was achieved for LV mass calculation. The stroke volumes for LV and RV were calculated with a mean percent error of -2.52% and -8.43%, respectively. We achieved a mean percent error of -3.22% for LV and -1.64% for RV ejection fraction. Conclusion The fully automated AI-based quantitative analysis of cine cardiac MR images developed in this study demonstrated high agreement with the ground truth across large datasets, including those from external centers. This method can significantly reduce the time required for image analysis and enhance the accuracy and consistency of cardiac quantitative assessments in clinical settings.

The role of semi-quantitative parameters of thallium-201 myocardial perfusion imaging in predicting mortality rate among CKD population

Abstract Background Chronic kidney disease (CKD) is a major public health concern worldwide, with high morbidity and mortality rates. Myocardial perfusion imaging (MPI) is a non-invasive diagnostic tool that can detect early-stage cardiovascular disease in CKD patients. Purpose This study aimed to investigate the role of semi-quantitative parameters of Thallium-201 MPI in predicting mortality rates among CKD patients. Methods This retrospective study included 579 CKD patients who underwent Thallium-201 MPI between October 2005 and December 2019. Semi-quantitative parameters were analyzed using automation software, including transient ischemic dilation (TID), lung-to-heart ratio (LHR), total perfusion deficit (TPD), summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), summed thickening percent (ST%), summed motion percent (SM%), stress end-diastolic volume (EDV), stress end-systolic volume (ESV), and stress left ventricular ejection fraction (LVEF). The primary endpoint was overall mortality. Results During a median follow-up of 52 months, 148 patients died. The older age group, lower hemoglobin levels, and lower estimated glomerular filtration rate (eGFR) were associated with higher mortality rates. The semi-quantitative parameters that predicted overall mortality included LHR above 0.4, elevated ST% , increased stress EDV and ESV, and reduced stress LVEF in a multivariable Cox regression model. Conclusion Thallium-201 MPI with semi-quantitative parameters can predict mortality rates in CKD patients without a definite diagnosis of coronary artery disease. The identified parameters, including LHR above 0.4, elevated ST levels, increased stress EDV and ESV, and reduced stress LVEF can assist in early detection the mortality risk in CKD patients.Characteristics of CKD PatientsMultivariable Analysis

Reduced stroke volume by resting 2-dimensional echocardiography negatively affects survival in patients with abnormal ejection fraction

Abstract Background Abnormal (<50%) ejection fraction (EF) is a cornerstone of risk stratification and therapy, but also an imperfect proxy of left ventricular (LV) cardiac pump function, better assessed with stroke volume (SV). Aim To assess the value of SV in stratifying risk of patients with abnormal EF. Methods In a prospective, observational, multicenter study, we recruited 746 patients (age 66± 11 years, 536 males, 72%, 359 with previous myocardial infarction, 48%) with chronic coronary syndromes (CCS) and EF <50% referred for resting transthoracic echocardiography with technically successful 2-dimensional volumetric echocardiography in 17 accredited laboratories. We quantitatively assessed LV end-diastolic volume (EDV) and end-systolic volume (ESV) by Simpson’s biplane method. EF (EDV-ESV/EDV) and SV (EDV-ESV) were calculated from LV volumes. The outcome end-point was all-cause death. Results EF was 39±9%, SV 48±20 ml. There were 100 all-cause deaths during a median follow-up of 796 days (interquartile range 420-1286 days). Receiver-operating curve analysis identified SV≤31.4 ml/b as the best cut-off for predicting mortality. At multivariable analysis, after adjustment for age and prior myocardial infarction, EF <40% and SV ≤31.4 ml/b were significantly associated with decreased survival (HR 2.09, 95%, confidence intervals 1.09-4.01, p=0.024). The annual mortality was lowest (3.19%) in the group with mildly reduced (40-49%) EF and normal (>31.4 ml) SV, and highest (8.30%) in patients with both reduced EF and abnormal SV: see figure. Conclusion Patients with CCS and abnormal EF are a prognostically heterogeneous group, and the mortality rate is almost 3-times worse in patients with reduced EF and abnormal SV compared to patients with mildly reduced EF and normal SV. A simple resting volumetric two-dimensional echocardiography can offer an efficient risk stratification, beyond EF, with no extra imaging or analysis time.Figure

Acute changes in right ventricular geometry and function following transcatheter tricuspid valve interventions

Abstract Background Little is known about acute changes in right ventricular (RV) function and geometry following transcatheter tricuspid edge-to-edge repair (T-TEER) or transcatheter tricuspid valve replacement (TTVR). Pressure-strain-volume loop-derived myocardial work metrics showed associations with myocardial energetics and contractility in conditions accompanied by volume overload, suggesting their potential utility in patients with tricuspid regurgitation (TR). Purpose To define acute changes in RV volumes and RV myocardial work following T-TEER and TTVR using conventional and pressure-strain-volume derived RV work metrics. Methods In this multicenter, observational study, 3D echocardiographic datasets and invasively acquired RV pressures were collected before and after transcatheter tricuspid valve procedure. Using dedicated software (ReVISION, Argus Cognitive) 3D RV volumes and strains were quantified and decomposed to longitudinal, radial and anterio-posterior motion. Forward stroke volume (SV) was calculated by subtracting TR volumes from RV 3D end-diastolic volume (EDV) and end-systolic volume (ESV) difference. Three-dimensional pressure-strain-volume loops were constructed and global RV work-index (RV-Wi) was calculated. Changes in RV parameters before and after the intervention were compared using paired-samples t test. Results Of 37 patients included in this study (65% male), 20 underwent T-TEER and 17 underwent TTVR. Compared to T-TEER patients, patients undergoing TTVR had higher prevalence of torrential TR at baseline but also achieved a higher reduction in TR volumes after the intervention (44 ± 11 ml vs 60 ± 16ml; p = 0,001). Following T-TEER there was a significant reduction in RV EDV (240 ± 93 ml vs 200 ± 80 ml; p < 0.001) and increase in SV (55 ± 34 ml vs 68 ± 26 ml; p = 0.036). Following TTVR there was a significant increase in RV ESV (121 ± 46 vs 146 ± 48, p = 0.003) and no significant change in SV (47 ± 24 ml vs 55 ± 20 ml; p = 0.143). There was significant reduction in RV strain and ejection fraction (EF) (all p < 0.001) primarily driven by reduction of radial motion component in both groups. RV-Wi increased in 35% (7/20) of T-TEER patients and in 18% of (3/17) TTVR patients. Conclusion An acute reduction in RV EF was observed in all patients and was mainly caused by decrease in RV EDV in T-TEER patients and increase in RV ESV in TTVR patients. Despite decrease of conventional metrics of RV function in both groups, an increase in RV-Wi was observed in 27% of all patients.Baseline and follow-up characteristicsCentral Figure

Non-lipid metabolomic biomarkers are associated with adverse cardiac remodelling and cardiovascular outcomes

Abstract Background Metabolomics is the detailed profiling of circulating metabolites including carbohydrates, lipids, amino and fatty acids, and ketones, all of which are substrates used in energy metabolism by cardiomyocytes. Purpose The role of cholesterol fractions with cardiovascular risk is well-established. This novel study examines the association between non-lipid circulating metabolites and markers of cardiac remodelling as assessed by cardiovascular magnetic resonance (CMR) imaging. Metabolites associated with adverse remodelling were taken forward to examine their impact on incident cardiovascular disease (CVD); ischaemic heart disease (IHD) and heart failure (HF). Methods This study used data from the UK Biobank. After exclusions (prevalent IHD, HF; outliers), there were a maximum of 34,727 individuals for CMR analyses and 262,536 individuals for incident CVD analysis. For CMR analyses, outcome variables were LV end-diastolic volume (EDV), LV mass, LV mass:volume ratio (MVR), LV global longitudinal strain (GLS) and native T1. Separate regression models were built for each of the 40 scaled metabolite biomarkers. Each model incorporated one metabolite at a time with additional covariates: age, sex, ethnicity, systolic blood pressure, cholesterol medication use, type 2 diabetes, dietary intake, smoking status, fasting time, and time between recruitment and CMR examination. A Bonferroni-corrected significance threshold of 2.4x10-4 was used. To account for correlation between metabolites, Lasso regression with 10 fold cross-validation to identify the most important predictors was performed for LV MVR, LV GLS and native T1 whereby all metabolites and above covariates were included in the model. Metabolite predictors of adverse remodelling were included in an adjusted logistic regression model with incident CVD as an outcome. Results Metabolites demonstrating significant (p < 2.4x10-4) associations with CMR parameters are presented in Fig 1. For higher LV MVR and more positive LV GLS, the metabolites with the largest effect were monounsaturated fatty acids and glycoprotein acetyls. Higher omega-6:omega-3 ratio was associated with higher T1 values. The Lasso model identified 8 important predictors for adverse cardiac remodelling. Of these, two were routine biomarkers (creatinine, glucose). Of the remainder, monounsaturated fatty acids, glycoprotein acetyls and apolipoprotein B:apolipoprotein A1 ratio were significantly associated with increased risk of incident CVD (Fig 2). Current evidence regarding monounsaturated fatty acids in CVD is mixed. Glycoprotein acetyls are implicated in vascular inflammation. Apolipoproteins are thought to be a potential therapeutic target for CVD risk reduction. Conclusion This study demonstrates a role of non-lipid metabolites on subclinical CVD as assessed by adverse remodelling with CMR as well as associations with incident CVD. We highlight potential novel biomarkers for identification of CVD.Metabolite association with LV MVR/GLSMetabolite association with incident CVD

Echocardiographic findings in newborns with inadequate intrauterine growth during pregnancy

Abstract Background Infants born small for gestational age (SGA) or diagnosed with fetal growth restriction (FGR) are at increased risk of neonatal mortality as well as cardiovascular disease later in life. Previous studies based on smaller cohorts (n<200) of newborns with SGA and FGR (n<200) have demonstrated structural and morphological alterations in the heart compared to infants born appropriate for gestational age (AGA). However, to our knowledge no previous study has systematically investigated the effect of SGA and FGR on echocardiographic parameters in the infant heart. Purpose To investigate whether echocardiographic parameters differ among infants born SGA or with FGR, in comparison to infants born AGA. Methods This study is a population-based cohort study of infants (n>25,000) offering postnatal cardiac examination including transthoracic echocardiography (TTE) between 2016-2018. We compared left ventricular (LV) TTE parameters in infants born SGA (birthweight ≥3rd and <10th percentile, n=2,106) and with FGR (birthweight <3rd percentile, n=972) with infants born AGA (birthweight ≥10th and <90th percentile, n=20,468) using a multiple linear regression analysis. We have investigated LV volumes, systolic function, diastolic function, and LV structure. All analyses were adjusted for sex, gestational age at birth, weight, length, and age at cardiac examination. Results Infants born SGA had higher heart rates compared with infants born AGA. Both infants born SGA and infants with FGR had significantly smaller LV dimensions including septal and posterior wall thicknesses (IVSd and LVPWd), and LV internal diameters (LVIDd and LVIDs). Infants born SGA had smaller end-diastolic and end-systolic volumes compared with infants born AGA (Table 1). Infants born SGA or with FGR had significantly higher mitral valve early peak velocities, compared with infants born AGA, and infants born SGA showed increased mitral valve atrial peak velocities indicating altered diastolic function (Table 1). Conclusion Infants born with inadequate intrauterine growth had smaller LV dimensions compared with infants born AGA, even when adjusting for infant size and age. Infants born SGA and with FGR both exhibited altered diastolic function. Longitudinal studies of children with inadequate intrauterine growth are needed to determine the impact on adult cardiac health.

Deep learning enables the fully automated quantification of high-resolution cardiac CT images: human in loop for model development

Abstract Introduction Cardiac computed tomography (CCT) images provide vast spatial and temporal information. Segmentation of the structure of interest is necessary to provide quantitative information. However, manual segmentation of cardiac substructures is highly time-consuming. Objective This study aims to develop a robust deep-learning segmentation model for cardiac substructure segmentation in 3D CCT images. Method We initially developed a 3D U-Net architecture, incorporating extensive augmentation, for the segmentation of the Left Ventricle Myocardium (LVM), the blood cavities of the Left and Right Ventricles (LV, RV), and the Left and Right Atria (LA, RA). This model utilized CT images from 20 patients who had available manual segmentation. Subsequently, we applied this initial model to datasets from two centers, including different generations of scanners. We then visually inspected the segmentation, selected the highest-quality segmentations, and modify it if necessary, and excluded the low-quality data. We continued fine-tuning the model with the new dataset until we reached a count of 456 patients. As there were multiple images from one patient during this model's development, we generated datasets to develop a new model using the entire new dataset to avoid any data leakage in the reported metrics. The model was developed using data from Center 1 (5-fold cross-validation) and then evaluated on an external test set from Center 2 (126 patients) and also 4D images from Center 1. Various metrics were calculated to assess the model's performance. Results In the internal test set, utilizing 5-fold CV, the model demonstrated high segmentation accuracy, achieving an overall Dice coefficient of 0.98, with individual scores of 0.96 for LVM, 0.98 for LV, 0.98 for RV, 0.99 for RA, and 0.98 for LA. We assessed the automatic quantification capability of the segmentation model from 256 patients, resulting in an R2 value greater than 0.92 for both LV end-diastolic and systolic volumes. In contrast, the model maintained robust performance on the external dataset, achieving an overall Dice coefficient of 0.96, with individual scores of 0.95 for LVM, 0.98 for LV, 0.97 for RV, 0.98 for RA, and 0.94 for LA. Conclusion We provided a large cohort of ground truth segmentations for different cardiac CT substructures using a human-in-the-loop strategy. Subsequently, we developed a deep learning model for highly accurate automated segmentation of these substructures. This model allows for fast and fully automatic segmentation and quantification of 3D and 4D cardiac CT images, from which various quantitative metrics can be extracted from different cardiac substructures.

Three dimensional biatrial expansion index as an independent predictor of outcome in dilated cardiomyopathy

Abstract Background Left atrial expansion index (LAEI) is a marker of left ventricular (LV) diastolic dysfunction and an outcome predictor in heart failure (HF). However, the role of the right atrial expansion index (RAEI) in the setting of left-sided HF is incompletely understood. Purpose We sought to evaluate the left, right and combined bi-atrial expansion index (BAEI) with three-dimensional (3D) echocardiography in a cohort of patients with dilated cardiomyopathy (DCM) and to assess their prognostic role. Methods We enrolled 121 consecutive patients (mean age 59±14 years, 74% men) with DCM in sinus rhythm, who underwent 3D echocardiography and were prospectively followed for 19±11 months for an endpoint of death, nonfatal cardiac arrest and HF hospitalization. As previously described, for the left atrium (LA), LAEI was measured as (3D LA Vmax – 3D LA Vmin) x 100/3D LA Vmin, where Vmax was the maximal end-systolic atrial volume and Vmin was the minimal end-diastolic atrial volume. For the right atrium (RA), RAEI was calculated as (3D RA Vmax – 3D RA Vmin) x 100/3D RA Vmin. BAEI was defined as the sum of LAEI and RAEI. Results 55 patients (46%) reached the endpoint: there were 27 deaths, 5 nonfatal cardiac arrests and 23 readmissions for HF. Patients with adverse outcome had lower LAEI (52±25 vs. 63±36, p=0.047), lower RAEI (57±29 vs. 70±32, p=0.02), lower BAEI (108±46 vs. 133±55, p=0.008). In univariate Cox regression, all three expansion indices were predictors of adverse events: HR=3.23 [95% CI, 1.45-7.20], p=0.004 for LAEI, HR=2.12 [95% CI, 1.24-3.61], p=0.006 for RAEI, HR=3.99 [95% CI, 1.70-9.36], p=0.001 for BAEI. We constructed a multivariable model with well-established event predictors in DCM and one expansion index at a time. After adjustment for age, left ventricular ejection fraction, mitral regurgitation severity and pulmonary artery systolic pressure, all three expansion indices remained independent predictors of the composite endpoint: HR=2.75 [95% CI, 1.18-6.38], p=0.02 for LAEI, HR=1.86 [95% CI, 1.04-3.31], p=0.04 for RAEI, HR=3.53 [95% CI, 1.46-8.51], p=0.005 for BAEI. BAEI yielded the highest incremental prognostic power (likelihood ratio chi2 test=14, p=0.03) on top of the baseline model consisting of age, left ventricular ejection fraction, mitral regurgitation severity and pulmonary artery systolic pressure (likelihood ratio chi2 test=9). Conclusion In DCM, 3D atrial expansion indices are significantly lower in patients with major adverse events, reflecting a more impaired atrial reservoir dysfunction. Both LAEI, RAEI and BAEI were independent outcome predictors in patients with DCM. Combining the left and right atrial expansion indices might improve risk stratification, since BAEI had the highest predictive value after adjustment for confounders.

Coronary microvascular dysfunction as assessed by cardiac MRI and its association with aerobic exercise capacity in dilated cardiomyopathy

Abstract Background Dilated cardiomyopathy (DCM) has a poor prognosis. Aerobic exercise capacity (peak VO2) is an independent predictor of mortality but the central mechanisms contributing to exercise intolerance in DCM are unknown. Purpose To characterise myocardial perfusion reserve (MPR) and determine if cardiovascular magnetic resonance (CMR) measures of structure, function and microvascular function are associated with aerobic exercise capacity in DCM. Methods Single centre, prospective, case-control comparison of adults with DCM and matched controls. Adenosine-stress perfusion CMR to assess cardiac structure, function and quantitative perfusion, and cardiopulmonary exercise testing (CPET) to determine peak VO2, was performed. Controls were propensity matched based on age, sex, body mass index and diabetes status, and between group comparison was adjusted for other key clinical characteristics (CMR: ethnicity and systolic blood pressure; CPET: ethnicity, systolic blood pressure, smoking history and lung disease). Comparison of perfusion in segments with and without late gadolinium enhancement was performed using mixed effects linear regression taking into account individual patient segmental perfusion. Pre-specified multivariable linear regression, including key clinical and cardiac variables, was undertaken in patients with DCM to identify independent associations with percentage predicted peak VO2, which incorporates age, sex, height and weight. Results Sixty-six patients with DCM (median age 61 years, 71% male) were matched to 66 controls (median age 59 years, 71% male). The DCM group had greater left ventricular (LV) end-diastolic and end-systolic volumes, lower systolic and diastolic function, and had more focal and diffuse fibrosis compared to controls (Table 1). There was lower rest (0.58±0.14 versus 0.65±0.17 mL/min/g; P=0.033) and stress (1.53±0.49 versus 2.01±0.60 mL/g/min; P<0.001) myocardial blood flow, and lower MPR (2.69±0.84 versus 3.15±0.84 mL/g/min; P=0.002) in the DCM group. In DCM patients, mixed effects linear regression demonstrated lower rest (adjusted mean 0.54(95% CI 0.50-0.57) versus 0.58(0.55-0.62) mL/g/min; P<0.001) and stress MBF (1.38(1.25-1.51) versus 1.55(1.43-1.67) mL/g/min; P<0.001) in segments with LGE compared to segments without LGE, but there was no difference in MPR (2.71(2.47-2.96) versus 2.76(2.55-2.97) mL/g/min; P=0.496). DCM patients had markedly lower peak VO2 (19.8±5.5 versus 25.2±7.3 mL/kg/min; P<0.001). Multivariable linear regression demonstrated that LV ejection fraction, extracellular volume fraction and MPR, but not LV mass, were independently associated with percentage predicted peak VO2 in DCM (R squared=0.531, P<0.001; Table 2). Conclusions DCM patients have lower rest and stress myocardial blood flow and lower MPR compared to controls. In DCM, MPR, LV ejection fraction and fibrosis are independently associated with aerobic exercise capacity.

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.

Predictors of LV reverse remodeling after SAVR: insights from a prospective TTE and CMR study in patients with severe aortic stenosis

Abstract Background Left ventricular (LV) remodeling in patients with severe aortic stenosis (AS) is believed to be reversible after pressure overload relieve, as provided by both surgical (SAVR) or transcatheter aortic valve replacement. However, LV reverse remodeling (RR) is far from uniform in patients with AS and the same clinical indication for treatment. Aim To determine the prevalence and imaging predictors of LV RR after SAVR in patients with severe symptomatic AS. Methods single-center, prospective cohort study enrolling 119 patients with severe symptomatic AS (age 71±8y, 49% male; mean transaortic gradient 62±18mmHg, mean indexed aortic valve area (AVAi) 0.40±0.10 cm2/m2, mean LV ejection fraction by TTE 58±9%), with no previous history of ischemic cardiomyopathy, undergoing SAVR between 2019 and 2022. All patients underwent serial imaging assessment beyond clinical characterization (transthoracic echocardiogram – TTE, and 1.5T cardiac magnetic resonance - CMR) prior to surgery and at the 3rd to 6th month post-SAVR. Endomyocardial biopsy (EMB) for myocardial fibrosis quantification (Masson ́s Trichrome histochemistry) was performed during SAVR. LV RR was defined when in presence of at least one of the imaging criteria: > 15% reduction in LV end-diastolic indexed volume (LVEDV) by CMR; > 15% reduction in LV indexed mass (LVM) by CMR; > 15% reduction in LV geometric remodeling by CMR; >10% increase in LV ejection fraction (LVEF) either from TTE or CMR; > 50% increase in global longitudinal strain (GLS) at TTE. Clinical, imaging and histology derived data were compared in patients with post-SAVR LV RR and for each of the defined criteria. Results 107 patients (90%) met at least one criteria of LV RR. Morphological criteria were more prevalent than LV functional improvement after SAVR (Figure 1). In patients who met at least one criteria of LV RR, no differences were found between NT- proBNP, LV tissue characterization (by CMR) or myocardial fibrosis at EMB. Yet, those with LV RR had significantly smaller preoperative AVAi (0.4±0.9 vs 0.5±0.9 cm2/m2, p=0.007) and higher mean valvular gradients (62±18 vs 49±12 mmHg, p=0.017). Considering individual LV RR criteria, patients with higher NT-proBNP levels met LVEF and morphological (LVEDV and LVM) LV RR criteria (p=0.027, p=0.016 and p= 0.003, respectively). Patients with higher % of late gadolinium enhancement on pre-operative CMR [7.8 (IQR 2.5-11.3) vs. 1.6 (IQR 0-5.2)%, p=0.017] had significant GLS improvement after SAVR. Conclusion In a cohort of patients with classical severe, symptomatic AS, LV RR is common after SAVR, occurring in almost 9 out of every 10 patients. Both indexes of worse valve narrowing and pre-operative LV adaptation are associated with favorable RR after surgery. This underlines the benefits of a timely intervention even in patients with more advanced disease.

Understanding the impact of heart failure treatment on cancer growth

Abstract Background Heart failure (HF) is associated with systemic alterations that extend beyond the cardiovascular system. The dysregulation of physiological pathways induced by HF, encompassing inflammatory or neurohormonal pathways, may foster an environment conducive to cancer growth and the spead of metastases. It is unknown whether these alterations are attenuated when HF is treated, and whether certain therapies for HF may yield more significant effects than others. Purpose This study aims to investigate whether myocardial infarction (MI)-induced left ventricular (LV) dysfunction promotes breast cancer growth and triggers the development of lung metastases. Additionally, it compares the potential impact of different therapeutic strategies for LV dysfunction on cancer development. Methods Myocardial infarction (MI) was induced in 11-week-old female BALB/c mice by ligation of the left anterior descending (LAD) coronary artery, leading to LV dysfunction and significant dilation within four weeks. Starting 2 weeks after surgery, mice with ejection fraction (EF) < 40% received daily oral gavage of vehicle or one of three drugs: carvedilol (10 mg/kg), enalapril (20 mg/kg), or empagliflozin (15 mg/kg). Four weeks post-surgery, 2x105 4T1 metastatic breast cancer cells were injected into the 4th mammary fat pad. Tumor volume was measured every two days, starting eight days after injection. Weekly echocardiographic assessments monitored cardiac function until the end of the experiment. Tumors were excised on day 22 after injection. Mice were euthanised on day 28 for post-mortem analysis. MCM2 proliferation staining was performed on lung tissue to quantify metastases. Results Among the HF treatments, only empagliflozin (n=11) induced a significant decrease in both left ventricular end-diastolic and end-systolic volume (Fig. 1.A; p=0.0043; Fig. 1.B; p=0.0186) compared to the vehicle group (n=11). Tumor weight and volume (Fig. 1.C-D) were not different in the HF/vehicle group (n=15) and the sham-operated group (n=13). Carvedilol (n=14) led to a small reduction in tumor weight (Fig. 1.C; p=0.1264), while empagliflozin (n=11) exhibited a significant reduction in both tumor weight (Fig. 1.C; p=0.0306) and volume (Fig. 1.D; p=0.0268). In addition, carvedilol (n=13) significantly reduced lung metastases (Fig. 1.E; p=0.0347) compared to the HF/vehicle group (n=13). Enalapril (n=10) and empagliflozin (n=9) did not significantly impact the development of lung metastases. Conclusion Despite the absence of increased cancer growth post-MI, our findings indicate that specific treatments for HF—namely, carvedilol and empagliflozin—attenuate cancer growth post-MI. Furthermore, carvedilol demonstrated potential in reducing metastatic spread. Additional research is required to uncover the underlying mechanisms both in the presence and absence of HF, and to explore the molecular impact that HF treatments have on various stages of cancer progression.Figure 1

Left atrial remodeling and novel biomarkers in obese patients with heart failure with preserved ejection fraction compared to type-2-diabetics and obese controls: a cardiac magnetic resonance study

Abstract Background Elevated filling pressures and subsequent left atrial (LA) dilation are common findings in heart failure with preserved ejection fraction (HFpEF), reflecting a chronic state of the disease and holding prognostic value. HFpEF is thought to develop through a long-term pro-inflammatory state triggered by comorbidities, such as obesity and type 2 diabetes mellitus (T2DM). Emerging biomarkers have shown associations with structural remodeling, but also increased myocardial stiffness. Purpose To elucidate the relationship between LA volume and function, and prognostic biomarkers (NT-proBNP, BNP-32, IL1R1, Galectin-3, and Pentraxin-3) in an obese cohort with T2DM or HFpEF and T2DM, versus healthy obese controls. Methods We conducted a prospective cohort study of 35 obese participants, divided into three groups: T2DM (n=16), HFpEF with T2DM (NYHA II-III, n=13), and healthy obese controls (n=6). Each subject underwent comprehensive CMR at a 3T scanner to assess LA strain and volume. Atrial strain was assessed on 2- and 4-chamber view cine images by experienced CMR investigators using dedicated software. Routine labs and serum levels of biomarkers were measured. If labs or images were repeated, the average was calculated. Statistical significance was determined through ANOVA and student’s t-test for group comparisons and Pearson correlation for associations between LA parameters and biomarker levels. Results Cohorts were evenly matched in terms of demographics, vital signs, and ventricular volumes and functions, as depicted in Table 1. Only one patient in the HFpEF subgroup reported history of atrial fibrillation. Both minimum and maximum LA volumes were significantly elevated in the HFpEF group compared to the T2DM and control groups (p < 0.018). LA strain (conduit, reservoir, and booster) was notably compromised in the HFpEF cohort, contrasting with the obese T2DM group where LA strain values did not differ significantly from those observed in obese controls (Figure 1). Biomarker analysis revealed a marked increase of NT-proBNP, BNP-32, Galectin-3, and Pentraxin-3 in the HFpEF cohort. In the HFpEF cohort, IL1R1 was the only biomarker that was strongly associated with higher left ventricular enddiastolic (r=0.69, p=0.003) and endsystolic volumes (r=0.75, p=0.009). Moreover, IL1R1 was the only biomarker associated with atrial functional changes (booster strain, r=-0.57, p=0.043) in the HFpEF patients. Our findings indicate that ILR1 plays a crucial role in the cardiometabolic (obesity-T2DM) HFpEF phenotype, with its activation leading to advanced cardiac remodeling. Conclusion Obese HFpEF patients with T2DM showed severely altered left atrial morphology and function compared to those that are only obese or obese with T2DM. Moreover, our findings revealed that atrial remodeling in this population is driven by pro-fibrotic inflammatory pathways.Characteristics of the study cohortLeft atrial strain analysis

CD14 blockade preserves left ventricular structure and systolic function in a murine model of ST-elevation myocardial infarction

Abstract Background Cluster of differentiation-14 (CD14) facilitates the excessive pro-inflammatory monocyte-macrophage response to myocardial injury. Both acute and chronic infiltration of pro-inflammatory macrophages are implicated in the immunological progression of ischemic heart failure. However, investigation of clinically practicable strategies of CD14 blockade are yet to be reported. Purpose This fully blinded and randomised preclinical study evaluated the efficacy of a neutralising anti-CD14 antibody given at reperfusion in a murine model of reperfused ST-elevation myocardial infarction (STEMI) with key clinical features. Methods Large anterior STEMI was induced in 48 adult mice by left anterior descending coronary artery occlusion for 1 h prior to reperfusion and randomisation to receive anti-CD14 antibody, isotype control (IgG2a) or saline weekly for four weeks (independently blinded). Outcome measures included functional assessments by 9.4T cardiac magnetic resonance (CMR) imaging and ultra-high-resolution echocardiography at 21- and 28-days post-STEMI, respectively. Results Multi-plane short axis CMR at 21-days post-STEMI revealed greater left ventricular (LV) ejection fraction in the anti-CD14 antibody-treated group compared with saline- and isotype-treated controls (30±1 vs 19±1 and 20±1 %, respectively, p<0.001; Figure 1A). CMR also revealed reduced LV dilatation with anti-CD14-treatment compared to control groups (76±5 vs 102±8 and 107±7 µl EDV in saline- and isotype-treated controls, respectively, p<0.05). Parasternal long axis echocardiography at 28 days post-STEMI confirmed that anti-CD14 antibody treatment was associated with greater LV systolic function compared to saline and isotype controls (30±1 vs 24±1 and 25±2 % EF, respectively, p<0.05; Figure 1B). Preservation of LV end-diastolic (86±4 vs 111±6 and 101±5 µl, p<0.01) and end-systolic (61±3 vs 84±5 and 77±5 µl, p<0.01) volumes was also observed with anti-CD14 treatment. Global longitudinal strain (GLS) of the LV was also significantly greater at 28 days post-STEMI with anti-CD14 treatment relative to saline and isotype controls (-8.5±0.4 vs -6.8±0.3 and -6.6±0.4 %, respectively, p<0.05). Conclusion(s) The findings of this fully blinded and randomised preclinical study provide evidence of a clinically practicable strategy of CD14 blockade initiated at reperfusion to mitigate progressive LV systolic dysfunction and dilatation post-STEMI.Figure 1.Functional outcome measures

Mechanical dyssynchrony and response to cardiac resynchronization therapy in heart failure patients with right ventricular pacing: a pre-specified subgroup analysis of the BUDAPEST CRT Upgrade trial

Abstract Introduction The BUDAPEST CRT Upgrade trial has established the strong clinical benefit of upgrading heart failure patients with a reduced left ventricular (LV) ejection fraction (HFrEF) and a high right ventricular pacing (RVP) burden to cardiac resynchronization therapy with defibrillator (CRT-D). Importantly, however, the CRT upgrade response is not homogeneous regarding LV reverse remodeling and associated clinical outcomes. The presence of mechanical dyssynchrony (MD) assessed by echocardiography has been linked to more CRT benefits; still, its change in response to CRT and added prognostic value in HFrEF patients with high RVP are scarcely investigated. Purpose Accordingly, we aimed to assess the prevalence, clinical characteristics, CRT response rate, and prognostic value of RVP-induced MD in the BUDAPEST CRT Upgrade cohort. Methods The multicentre, randomized, controlled trial enrolled 360 HFrEF patients with a pacemaker or implantable cardioverter defibrillator (ICD) and significant RVP (≥ 20%) who were randomly assigned to receive CRT-D upgrade or ICD in a 3:2 ratio. Protocol echocardiography was performed at baseline and at 12-month follow-up visits and was evaluated at a central core lab. Beyond LV end-diastolic (EDV) and end-systolic volumes (ESV), longitudinal strain-derived septal deformation patterns by speckle tracking were assessed to determine the presence of RVP-induced MD. The endpoints were volumetric non-response (defined by a relative decrease in LV ESV <15%) and the composite of volumetric non-response or HF hospitalization. Results The echocardiographic assessment was feasible in 325 patients at baseline; 133 (41%) patients presented with MD. Females were more likely to present with MD (female vs. male, 65% vs. 38%, p=0.003). MD patients had higher LV EDV (MD vs. no-MD, 248±78 vs. 219±78 mL, p=0.001) and LV ESV (190±67 vs. 165±64 mL, p<0.001) at baseline. In the CRT-D group, 126 (75%) patients were volumetric responders, and 41 (25%) were non-responders at 12 months. CRT patients with baseline MD were less likely to experience volumetric non-response (OR 0.35 [95% CI 0.15-0.82], p=0.015) or the composite endpoint (OR 0.37 [95% CI 0.17-0.77], p=0.008). Out of 57 CRT patients with baseline MD who had follow-up assessment available, 52 (91%) patients had a favorable change: the MD pattern disappeared. Patients with MD resolution at 12 months were less likely to experience volumetric non-response or the composite endpoint (OR 0.39 [95% CI 0.17-0.93], p=0.034; OR 0.38 [95% CI 0.16-0.86], p=0.021, respectively). CRT patients with resolved MD were less likely of ischemic etiology and had 100% posterior or lateral LV lead location. Conclusions The presence of RVP-induced MD and its resolution is associated with better clinical response in HFrEF patients undergoing CRT-D upgrade. MD assessment can refine patient selection algorithms of CRT.Figure 1