Left Ventricular End-systolic Volume Research Articles

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

Prognostic value of echocardiographic parameters in predicting major adverse cardiac events one year following st-segment elevation myocardial infarction

Abstract Approximately 50% of patients who survive an ST-segment elevation myocardial infarction (STEMI) experience irreversible damage to the heart muscle, which increases long-term risk of developing heart failure. Moreover, cardiovascular mortality constitutes half of all deaths. This research aimed to determine the best combination of patient data collected during a one-year follow-up period to enhance the accuracy of outcome predictions for patients with STEMI. Methods In this study, 246 patients who experienced STEMI and older than 18 were prospectively monitored. All participants received primary percutaneous coronary intervention treatment. The study's primary outcomes, observed over the year following hospital discharge, included cardiovascular death, recurrent myocardial infarction, newly diagnosed heart failure, and arrhythmias or conduction issues. Of the patients, 18% of patients reached the primary outcomes. Two-dimensional transthoracic echocardiography was conducted 3-5 days after the initial event to assess left ventricular global longitudinal strain (GLS) using 2D speckle-tracking echocardiography on the apical four-chamber, two-chamber, and long-axis views. Left ventricular mechanical dispersion was calculated as the standard deviation of the time from the Q/R wave onset to peak GLS across 17 segments of the left ventricle. Results The findings revealed that the overall GLS was -10.70 (-12.61 to -8.40), but in patients who met the study's primary outcomes, GLS was significantly lower at -7.83 (-8.70 to -6.90), compared to -12.02 (-13.11 to -10.17) in those who did not, with a significant difference (p=0.00001). Mechanical dispersion was 40.24±26.56 in the entire cohort but significantly higher at 65.62±22.57 in the outcome group compared to 25.79±14.81 in the non-outcome group (p=0.00001). The ejection fraction averaged 48.97±7.69% across all patients, 47.22±7.16% in those with outcomes, and 49.92±7.84% in those without, with a statistically significant difference (p=0.039). Cox regression analysis identified key predictors of major adverse cardiac events (MACE) within one year after STEMI, including global longitudinal strain (p=0.0006), left atrium volume index (p=0.0448), left ventricular end-diastolic diameter (p=0.045), and mechanical dispersion (p<0.0001). A multivariate logistic regression analysis demonstrated that a combination of GLS, left ventricular end-systolic volume (LVESV), mechanical dispersion, and ejection fraction could predict 1-year MACE with high accuracy (χ2 = 85.18; p<0.0001, AUC=0.961 [0.903-0.989]). In conclusion, this study identifies crucial metrics, such as global longitudinal strain, left ventricular end-systolic volume, mechanical dispersion, and ejection fraction, as predictive factors for MACE one year following STEMI. This predictive model is straightforward, reproducible, and can be easily implemented in cardiology practice.

Elucidating the mechanism of rapid functional recovery following atrial fibrillation ablation in patients with left ventricular systolic dysfunction

Abstract Introduction Successful sinus rhythm restoration by catheter ablation (CA) of atrial fibrillation (AF) rapidly improves cardiac function in patients with left ventricular (LV) systolic dysfunction. However, the underlying mechanism of this recovery remains unknown. Purpose To elucidate the mechanism of the functional recovery after CA of AF and systolic dysfunction. Methods We retrospectively examined 4001 consecutive patients who underwent first-time CA of AF between 2012 and 2021 at our institution. Of them, 505 patients had baseline LV ejection fraction (LVEF) of <50%. Among them, we enrolled 454 patients who received electrocardiogram-gated contrast-enhanced 256-slice multi-detector computed tomography (MDCT) (Brilliance iCT, Philips Medical Systems, Cleveland, Ohio) both at baseline and 3 months after CA. Changes in LV measures, wall thickness, and LV mass were examined based on MDCT data. Results A reduction of LV end-systolic volume (LVESV) (from 71 ± 37 ml to 46 ± 34 ml, p <0.001) and improvement of LVEF (from 39 ± 9% to 62 ± 14%, p <0.001) were observed after CA. However, there was no significant change in LV end-diastolic volume (LVEDV) (from 118 ± 49 ml to 116 ± 46 ml, p = 0.13). Mean wall thickness during diastole did not change (from 7.1 ± 1.4 mm to 7.1 ± 1.4 mm, p = 0.94), either. However, wall thickness during systole significantly changed after CA (from 10.0 ± 1.7 mm to 12.7 ± 2.8 mm, p <0.001). As a result, there was no significant change in LV mass after CA (from 84.3 ± 28.7 g to 84.4 ± 28.1 g, p = 0.88). A regression analysis revealed a significant inverse correlation between the delta LVEF and delta LVESV (r = -0.59, p <0.001). However, the delta LVEF was not correlated with the delta LVEDV and delta LV mass. Conclusions The rapid improvement of LVEF after CA of AF was attributed to a decrease in the LVESV. Unchanged LV mass indicated that this functional recovery was solely a mechanical issue, without evidence of myocyte regression.

The impact of multimorbidity on cardiac remodelling in the UK Biobank

Abstract Background/Introduction Previous work has suggested that multimorbidity is associated with higher all-cause mortality and cardiovascular mortality in the UK Biobank (UKB). The impact of multimorbidity on cardiac remodelling as measured by cardiovascular magnetic resonance (CMR) has not been studied in large cohorts. Purpose To determine if CMR biomarkers act as surrogates for adverse cardiovascular outcomes in multimorbidity. Method We analysed 44957 UKB participants who had CMR. Self-reported cancer (UKB field ID 20001) and non-cancer illnesses (UKB field ID 20002) were used to calculate comorbidity count with multi-morbidity defined as 2 or more illnesses. The predictive value of comorbidity count (exposure counts measured in quintiles) on CMR traits (outcomes) was evaluated using a univariable and multivariable generalised linear model. Covariates included sex, age, BMI, smoking status, regular alcohol intake, and the Townsend deprivation index, a measure of socioeconomic deprivation. The first model utilised univariable regression without covariates with subsequent iterations including age and sex and then all covariates. An interaction term was included for age and sex and a quadratic term for age in the models. CMR outcome measures were indexed left ventricular mass (LVM), indexed left ventricular end diastolic volume (LVEDV), indexed left ventricular end systolic volume (LVESV), indexed left ventricular stroke volume (LVSV), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), and indexed maximal left atrial volume (LA). The absolute value of GLS was used in the regression models. Variance inflation factor testing was used to check for collinearity. Analyses were completed using R v4.1.1. Results Median comorbidity count was 2. The burden of long-term conditions in this population of European ancestry with largely healthy individuals is lower than in other large population cohorts. Table 1 summarises multivariable analyses for comorbidity count, LVM and GLS. Due to high collinearity relating to age in the model, we centred age around the mean. LVM was higher with multimorbidity (top quintile Beta 0.63 (95% CI 0.23 to 1.04), P = 2.21x10-03). GLS was lower with multimorbidity (top quintile Beta -0.29 (95%CI -0.42 to 0.16), P = 8.10x10-6). LA volume was lower with multimorbidity (top quintile Beta -0.63(95% CI -1.22 to 0.04), P = 3.53 x 10-2). LVEF and other volume measures were not associated with multimorbidity. Conclusion Multimorbidity in this large cohort was associated with adverse cardiac structural and functional remodelling on CMR. These include a lower global longitudinal strain and higher LV mass.

Cardiac MRI traits linked to cardiomyopathy mutations in phenotype naive carriers

Abstract Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are prevalent forms of cardiomyopathies, characterised by changes in cardiac structure and function, associated with an increased risk of atrial fibrillation (AF), heart failure (HF), and sudden cardiac death (SCD). Due to these potential life-threatening consequences close monitoring of genetic mutation carriers of HCM and DCM, is important. However, disease onset in these subjects is highly variable, with a substantial subset of people only developing disease late-in-life, or not at all, making risk stratification challenging. We set out to identify cardiac MRI (CMR) based imaging biomarkers of HCM and DCM carriership in phenotype naïve individuals, which were benchmarked against associations with AF and HF. CMR and whole genome sequencing (n: 42,723) data were sourced from a UK biobank sample free of heart failure at the time of CMR measurements. A previously validated deep learning(DL) network was used to derive 22 CMR traits(1). Adjusted cox regression models were used to determine the CMR associations with the onset of heart failure and atrial fibrillation, providing empirical validation of the DL CMR network. Univariable and multivariable generalised linear models were employed to identify associations with genetic carriership conditional on cardiac risk factors. 14 and 19 CMR measurements were associated with the time until HF (274 cases), AF (704 cases), respectively. These variables included left-ventricle (LV) ejection fraction (EF), LV end systolic volume (ESV), Right-ventricular (RV) EF and right atrial (RA) EF. Using WGS data we identified 154 people with an HCM mutation and 220 with a DCM mutation, where HCM carriership associated with five and DCM with four CMR traits. This included RA-EF (OR 1.26 95%CI 1.10; 1.45), and RV-EF (OR 1.41 95%CI 1.23;1,63) for HCM, and LV-EF (OR 0.72 95%CI 0.62; 0.84), and RV stroke volume (OR 0.75 95CI 0.62; 0.91) for DCM. By combining deep learning of CMR with large sample size WGS we were able to identify cardiac imaging biomarkers of HCM and DCM carriership in apparently healthy subjects. This could prove relevant for early identification and monitoring of phenotype naïve people.

Additive effect of metabolic dysfunction-associated fatty liver disease on left ventricular function and global strain in type 2 diabetes mellitus patients: a 3.0 T CMR feature tracking study

Abstract Purpose Type 2 diabetes mellitus (T2DM) represents the most prevalent form of diabetes, exerting a significant influence on cardiovascular health. Concurrently, metabolic dysfunction-associated fatty liver disease (MAFLD) is closely linked to heightened cardiac dysfunction risk. Our study aimed to explore the additive effect of MAFLD on left ventricular (LV) deformation among T2DM patients, utilizing cardiac magnetic resonance (CMR) feature tracking technology. Methods This study retrospectively included 270 patients with T2DM, comprising 110 individuals with MAFLD and 160 without, alongside 80 age- and sex-matched healthy controls, all of whom underwent CMR examination. Parameters derived from CMR encompass those related to LV function and global strain metrics. LV global strain parameters include global radial peak strain (GRPS), longitudinal peak strain (GLPS), and circumferential peak strain (GCPS), peak systolic strain rate (PSSR), and peak diastolic strain rate (PDSR), measured across radial, circumferential, and longitudinal directions. Intergroup analysis, employing the Mann-Whitney U test, was utilized to compare LV function and global strain parameters. Results The LV function parameters, including LV end-diastolic volume (LVEDV), LVEDV index, LV end-systolic volume (LVESV), LVESVI, LV mass, and LV mass index, displayed a progressive augmentation from controls through T2DM patients without MAFLD, to those with MAFLD. In parallel, LVEF showed a declining trajectory across these groups. In contrast, LVSV and LVSVI were comparable among the three groups. In a similar vein, when examining global strain parameters derived from CMR, a significant and progressive deterioration is observed across the groups. GRPS, GCPS and GLPS, along with PSSR and PDSR in radial, circumferential, and longitudinal directions, manifest a pronounced decline moving from control subjects to T2DM patients without MAFLD, and further deteriorating in those with T2DM and MAFLD (All p-values < 0.05). To assess the effect of MAFLD severity on global peak strain, patients with T2DM and MAFLD were stratified into two groups: a mild MAFLD group (N=77) and a moderate to severe MAFLD group (N=33). Although there was a noticeable decline in GRPS, GCPS and GLPS, as well as in PSSR and PDSR across the three groups—from those without MAFLD to those with mild and then moderate to severe MAFLD—the observed differences did not reach statistical significance. The absence of statistical significance is likely due to the small sample sizes of the groups categorized by severity of MAFLD. Conclusions This study revealed that MAFLD has additive worsening effects on LV function and LV global strains in T2DM patients evaluated by CMR. Besides, moderate to severe MAFLD, compared to mild MAFLD, exhibits worse global strain parameters. Early detection and intervention of MAFLD might improve the prognosis of T2DM patients.

Efficacy and safety of of SGLT2 ihibtors in post mi patients: a systematic review and meta-analysis of RCTs

Abstract Introduction Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have demonstrated a decrease in cardiovascular (CV) events, especially in diabetic patients. However, it remains unclear whether the early administration of SGLT2is confers cardioprotective benefits following acute myocardial infarction (AMI). Purpose Our objective is to explore the in-hospital and long-term prognoses of patients presenting with AMI who are treated with SGLT2is compared to non-SGLT2is users. Methods We conducted comprehensive searches across PubMed, CENTRAL, WOS, Scopus, and EMBASE until October 2023. Pooled data were reported using risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, along with a 95% confidence interval (CI). This systematic review and meta-analysis is registered with PROSPERO. Results We included 14 studies with a total of 37,038 patients. Compared to non-SGLT-2 inhibitors, SGLT-2 inhibitors were associated with a decreased incidence of major adverse cardiovascular events (MACE) (RR: 0.60 with 95% CI [0.45, 0.82], P< 0.01), all-cause mortality (RR: 0.67 with 95% CI [0.55, 0.81], P< 0.01), heart failure (RR: 0.68 with 95% CI [0.57, 0.80], P< 0.01), stroke (RR: 0.67 with 95% CI [0.45, 0.99], P= 0.04), increased left ventricular ejection fraction (MD: 2.45 with 95% CI [0.81, 4.09], P< 0.01), and decreased left ventricular end-systolic volume (MD: -5.72 with 95% CI [-10.76, -0.67], P= 0.03). Conclusion SGLT-2 inhibitors significantly decrease MACE, all-cause mortality, heart failure, left ventricular ejection fraction, and left ventricular end-systolic volume in myocardial infarction patients.Figure 1Figure 2

AI-based cluster analysis enables outcomes prediction among patients with increased LVM

Abstract Background The traditional classification of left ventricular hypertrophy (LVH) solely based on left ventricular geometry disregards associated comorbidities and clinical characteristics. We aimed to identify unique clinical phenotypes of LVH using unsupervised cluster analysis and explore their association with clinical outcomes. Methods From UK Biobank (UKBB) participants with available left ventricular mass (LVM) estimations, we identified those meeting CMR-based criteria for increased LVM: LVM index ≥ 72 g/m2 for males and LVM index ≥ 55 g/m2 for females. Baseline demographic, clinical, and laboratory data were collected. Using Ward's method, patients were clustered based on 27 variables. The primary outcome was a composite of all-cause mortality with heart failure (HF) admissions, ventricular arrhythmia, and atrial fibrillation (AF). Cox proportional hazard model and Kaplan-Meier survival analysis were applied. Results Among CMR-assessed UKBB participants, 4,255 individuals exhibited increased LVM, with an average age of 64 ± 7 years; 2,447 (58%) were females. Cluster analysis identified four distinct subgroups. Over a median 5-year follow-up (IQR: 4-6), 100 patients (2%) died, 118 (2.8%) were hospitalized due to HF, 29 (0.7%) were hospitalized due to VA, and 208 (5%) were hospitalized due to AF. Univariate Cox analysis revealed that compared to the 1st cluster (n=1,578), patients in the 2nd (n=1,296), 3rd (n=824) and 4th (n=557) clusters had 60%, 104%, and 164% increased risk of a major event, respectively (95% CI 1.2-2.16, p<.001 for cluster 2; 95% CI 1.49-2.78, p<.001 for cluster 3; 95% CI 1.92-3.62, p<.001 for cluster 4). Each cluster manifested different phenotypes: cluster 2 comprised mainly overweight females, with the highest prevalence of chronic lung disease; cluster 3, predominantly composed of males, had the highest burden of comorbidities and cardiovascular risk factors; and cluster 4, mostly males, presented with the most abnormal cardiac measures, including left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and left ventricular ejection fraction (LVEF). Conclusions Unsupervised cluster analysis identified four subgroups among patients with increased LVM. These subgroups bear notable relevance to overall mortality risk and clinical outcomes. This phenotypic classification holds promise in offering valuable insights regarding clinical course and outcomes in LVH patients.

Prognostic value of multiparametric cardiac magnetic resonance after revascularized STEMI

Abstract Despite early revascularization of STEMI through angioplasty, the prognosis following STEMI remains poor for a non-negligible percentage of patients (1). In this setting, multiple imaging parameters have demonstrated their prognostic value. The aim of the present study is to evaluate which of these parameters are the most potent predictors of events following revascularized STEMI. Methods A prospective observational study was conducted, including a cohort of revascularized STEMI patients and who underwent cardiac MRI during the first week. The protocol included cardiac functional analysis and with b-SSFP sequences for evaluation of volumes, mass, ejection fraction and also circumferential and radial strain with feature tracking. STIR sequences were used to assess edema and salvaged myocardium, IR-FGE sequences were employed for evaluation of necrosis size and microvascular obstruction. Intra-infarct hemorrhage assessment was performed using T2* mapping sequences as previosly described (2,3,4) . A semi-automatic analysis was conducted, considering as microvascular obstruction segments with hypointensity in the infarct core and as segments with hemorrhage those with a T2* less than 20 ms. The association of imaging parameters with cardiovascular events in the first year following STEMI was studied using ROC curves. Variables with significant association were analyzed using a multivariate logistic regression model. Results Ninety-four patients with a mean age of 63 (SD 13) years were included. Nine of them had cardiovascular events in the first year and two of them died. The relative extent of necrosis and microvascular obstruction, minimal radial strain, left ventricular ejection fraction (LVEF) and indexed left ventricular end- systolic volume (ILVESV) showed significant association with cardiovascular events after STEMI. Variables with significant association were entered into a multivariate predictive model, revealing that the extent of microvascular obstruction (OR: 1.9, p=0.02) and the left ventricular end-systolic volume (OR: 1.04, p<0.01) are the only independent predictors of cardiovascular events following STEMI. Conclusion Although multiple imaging parameters have shown prognostic value after STEMI, the ILVESV and the extent of microvascular obstruction are the only independent predictors of events following STEMI.Multiparametric cardiac MR in STEMIAREA UNDER ROC CURVE OF CMR PARAMETERS

Association between GDF-15 levels and cardiac morphology and function in cardiac magnetic resonance imaging: insights from UK Biobank data analysis

Abstract Background/Introduction Growth Differentiation Factor-15 (GDF-15) has emerged as a biomarker associated with cardiovascular disease and adverse cardiac outcomes. Cardiac morphology and function, assessed through cardiac magnetic resonance imaging (CMR), are critical indicators of cardiovascular pathology. Understanding the relationship between GDF-15 levels and LV characteristics could provide valuable insights into cardiac pathophysiology and disease progression. Purpose This study aims to investigate the association between GDF-15 levels and cardiac morphology and function, utilizing data from the UK Biobank and CMR. By analyzing various CMR-derived parameters, including LV strain, myocardial mass, LV mass-to-volume ratio, ventricular and atrial volumes, we seek to elucidate the impact of GDF-15 on cardiac structure and function. Methods Data from the UK Biobank, including 2,264 participants, were analyzed. The median age of the analyzed participants was 55 years, with a median BMI of 26.0. Among the participants, 53% were females and 47% were males. CMR-derived variables related to cardiac morphology and function, along with GDF-15 levels, were examined. Multiple linear regression models were constructed to assess the association between GDF-15 levels and cardiac parameters, adjusting for age, sex, and other relevant covariates. Confidence intervals (CI) and p-values were calculated to determine the significance of observed associations. Results Analysis of the UK Biobank data revealed significant associations between GDF-15 levels and specific cardiac parameters (table1). Notably, GDF-15 levels were negatively associated with LV myocardial mass (LVM)(coefficient = -1.146, p = 0.0071), LV end-diastolic volume LVEDV)(coefficient = -3.321, p < 0.0001), LV end-systolic volume (coefficient = -1.876, p < 0.0001), as well as right atrial maximum volume (coefficient = -3.025, p < 0.0001) and minimum volume (coefficient = -1.858, p = 0.0003). In addition, LVM/LVEDV was positively associated with GDF-15 level (p<0.03). However, no significant associations were observed between GDF-15 levels and LV strain parameters, ejection fraction, or left atrial volumes. Conclusion This study provides evidence of a significant association between GDF-15 levels and selected parameters of cardiac morphology and function, as assessed by CMR in the UK Biobank population. These findings suggest a potential role of GDF-15 in modulating specific aspects of cardiac structure, function and left ventricle concentric remodeling warranting further investigation.GDF 15

Left ventricular end-systolic and diastolic elastance as predictors of cardiac events in patients who underwent mitral valve surgery for severe mitral regurgitation

Abstract Background/Introduction In severe mitral regurgitation (MR), the prognostic significance of left ventricular ejection fraction (LVEF) and LV dimensions is well-established. However, the assessment of diastolic function in this patient presents a notable challenge, and its impact on postoperative outcomes remains unclear. Purpose This study was designed to explore the potential of LV end-systolic (Ees) and diastolic elastance (Eed) as novel predictors for cardiac events following surgery. Methods A retrospective cohort study was performed on 199 patients (53% male, average age 60 years, mean LVEF 60.0%) with severe MR and undergoing surgery. Preoperative Ees and Eed were calculated using established formulas: Ees = (systolic blood pressure x 0.9) / LV end-systolic volume, and Eed = left atrial pressure / stroke volume, with left atrial pressure estimated from mitral Doppler flow parameters as SBP – (4 x peak MR velocity²). The primary outcome was defined as either cardiac death or hospitalization due to heart failure. Results Average values for Ees and Eed were 2.61 (IQR: 1.67-3.20) and 0.32 (IQR: 0.05-0.57), respectively. Univariate analysis indicated Ees (HR: 1.24, 95% CI: 0.99-1.57, p = 0.066) and Eed (HR: 5.93, 95% CI: 2.87-12.26) as potential predictors. Adjusting for age, LVEF, and LV dimensions, Eed remained an independent predictor of cardiac events (HR: 5.89, 95% CI: 2.81-12.28). Stratifying Eed at a threshold of 0.31—identified as best sum of sensitivity and specificity—revealed that Eed > 0.31 were associated with a 3.9-fold increase in cardiac events compared to those with Eed ≤ 0.31 (p = 0.008). (Fig.) Conclusions The assessment of Eed is a straightforward and readily available parameter in routine clinical practice. Our findings advocate for the inclusion of preoperative Eed evaluation as an independent prognostic indicator for patients undergoing surgery for severe MR.Event free survival by Eed

Predictors of hypercontractile heart phenotype in patients with chronic coronary syndromes

Abstract Background Hypercontractile phenotype of the left ventricle (LV) is an actionable therapeutic target in patients with chronic coronary syndromes (CCS), but its clinical recognition remains elusive. Purpose To assess the clinical variables associated with the hypercontractile phenotype of the LV, identified with supernormal values of an index of LV contractility such as LV force, also known as ventricular elastance. Methods In a prospective, observational, multicenter study, we recruited 5,122 patients (age 65± 11.1 years, 2974 males, 58%) with CCS referred for resting transthoracic echocardiography with technically successful volumetric echocardiography in 17 accredited laboratories. We measured systolic blood pressure (SBP) with a cuff sphygmomanometer. We assessed semi-quantitatively wall motion score index (WMSI), and quantitatively LV end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), force (SBP/ESV), stroke volume (SV), arterial elastance (SBP/SV), ventricular-arterial coupling (VAC, as SV/ESV), and cardiac output (CO = SV*heart rate).Univariable and multivariable logistic regression analysis assessed independent factors associated with the highest force sextile. Odds ratios (ORs) with the corresponding 95% confidence interval (CI) were estimated. Results For all the studied patients, EF was 59±11%. Force was 4.51±2.11 mmHg/ml, with reference sextile = 3.50-4.26 mmHg/ml, lowest sextile (Group 1) <2.60 mmHg/ml and highest sextile (Group 6) > 6.36 mmHg/ml. The correlation between the log of EF and the log of Force was significant with linear regression (r = 0.73, p < 0.001). Patients in the highest sextile of force showed lower values of WMSI, SV, EDV, and ESV, and higher values of arterial elastance and VAC (Table). By multivariable logistic regression model, the highest sextile of force was associated with age > 71 years (OR 4.35, 95% CI 3.06-6.18, p < 0.001), female sex (OR 4.48, 95% CI 3.62-5.54, p < 0.001), absence of beta-blocker therapy (OR 1.56, 95% CI 1.27-1.91), rest SBP> 159 mmHg (OR 6.86, 95% CI 5.03-9.35, p < 0.001), high heart rate (OR 1.03, 95% CI 1.02-1.04, p < 0.001), absence of prior MI (OR 1.31, 95% CI 1-1.72, p = 0.049), and higher LV EF at rest (OR 1.24, 95% CI 1.22-1.26, p < 0.001). Conclusions A hypercontractile phenotype of the LV with high force is associated with a small heart, reduced SV, and higher arterial elastance. It was clinically associated with advanced age, female sex, history of hypertension, absence of beta-blocker therapy, and high resting SBP.

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

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

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.

Type 2 diabetes individuals have a shorter QRS duration, prolonged QTc interval, flatter T wave, and reduced left ventricular cycle volumes compared to matched controls in the UK Biobank

Abstract Background Type 2 diabetes is associated with an increased risk of heart failure even in the absence of overt coronary artery disease, though underlying mechanisms are unclear. ECG and cardiac magnetic resonance (CMR) imaging provide windows into subclinical changes in myocardial structure and function and could be exploited to understand this. Purpose We investigate differences in ECG and CMR biomarkers in a large cohort of participants with type 2 diabetes, compared to a matched control cohort. We hypothesise that individuals with diabetes may exhibit concurrent differences in biomarkers, reflecting underlying cardiac remodelling. Methods We carried out a pair-matched cross-sectional study to examine the association between type 2 diabetes and multi-modal cardiac biomarkers. The exposure cohort consists of 1,781 UK Biobank participants with an imaging and ECG visit, prevalent type 2 diabetes and no known cardiovascular events at the time of visit. The control cohort is matched on age, sex and body mass index (BMI), and consists of 1,781 participants without diabetes. ECG and CMR biomarkers derived from UK Biobank data were used as outcome variables. We built four multiple multivariate linear regression models, incrementally adjusted for socio-demographic, lifestyle, and clinical covariates. Results Both cohorts were mostly male (63.6%), had a median age of 67 years [IQR: 72-85] and a median BMI of 27.8 kg/m2 [24.6-31.0]. Individuals with type 2 diabetes were more likely to be non-white (7.9% vs 2.7%, p<0.001), current or previous smokers (43.6% vs 40.6%, p=0.04), have lower diastolic blood pressure (79 [72-85] vs 81 [74-88] mmHg, p<0.001), and take cholesterol medication (72.3% vs 27.2%, p<0.001); anti-hypertensives (56.3% vs 27.3%, p<0.001); insulin (13.7% vs 0.1%, p<0.001); and metformin (53.1% vs 0.1%, p<0.001). They had a higher ventricular rate, shorter QRS duration, longer QTc interval, and flatter T wave amplitude, as well as lower left ventricular end-diastolic and end-systolic volumes, among other differences (Table 1). Covariates including cholesterol medication, metformin, and HbA1c were excluded as they were strongly correlated with diabetes, age and/or sex (Pearson correlation coefficient >0.3 or <-0.3). After full adjustment, we found that the exposure variable, diabetes, had a statistically significant association with ventricular rate, QRS duration, T wave offset, T wave amplitude in lead V3, left ventricular stroke volume and global average thickness (p<0.05) (Table 2). Conclusion Our results reveal that individuals with type 2 diabetes exhibit a shorter QRS, longer QTc, and lower end-diastolic and end-systolic volumes, compared to matched controls. This may be indicative of subclinical cardiac abnormalities, both electrophysiological and mechanical. Our association analysis suggests that other factors correlated with diabetes may be also responsible for certain biomarker differences and their underlying causes.

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

Left atrial reservoir strain as a prognostic indicator for cardiovascular events after mitral valvuloplasty

Abstract Background In patients after mitral valvuloplasty (MVP), assessing valve function and heart failure (HF) is crucial for prognostic predictions. Left ventricular diastolic function assessed by transthoracic echocardiography (TTE) plays an important role in the evaluation of HF in general practice. However, post-mitral valve surgery patients are excluded from the left ventricular diastolic function assessment guidelines proposed by the American Society of Echocardiography in 2016 due to their low correlation with left ventricular diastolic function indices. On the contrary, the left atrial reservoir strain (LARS) before MVP is considered as a prognostic factor, reflecting left atrial dysfunction caused by mitral regurgitation. Nevertheless, there are limited reports on the relationship between LARS and cardiovascular (CV) events after MVP. Purpose The study aims to investigate the utility of LARS in predicting CV events after MVP. Methods The study included 249 patients who underwent TTE between January 2011 and January 2023 after MVP at our hospital. Patient background data, including NYHA classification, medical history, medications, blood tests, and TTE data, were collected at the time of follow-up TTE. LARS, left ventricular global longitudinal strain (LV-GLS), and right ventricular free wall strain (RV-FWSL) analysis were performed using a vender-independent external strain analysis software for all patients in the cohort. The primary endpoints were cardiovascular death and HF rehospitalization. The predictor of cardiovascular events was assessed using the Cox proportional hazards model and Kaplan-Meier curve (KMC). Results The mean age was 61±14 years, and 159 patients (64%) were male. The median time from surgery to TTE was 4.8 (1.0-6.8) years, 32 patients (13%) had events within 8.5 (3.7-10.8) years after TTE. The event groups had higher age, NYHA classification, and NT-pro BNP compared to the non-event group. TTE parameters such as left ventricular mass index, left ventricular end-diastolic volume and end-systolic volume were larger, and LV-GLS and LARS were significantly lower in the event group. In multivariate Cox proportional hazards models showed that LARS was also a prognostic indicator even after adjustment for several variables (Table 1). The KMC showed that LARS was associated with events regardless of left atrial volume index (Log-rank p <0.001, chi-square:31.03) (Figure 1). Conclusion LARS was strongly associated with CV events after MVP. We consider LARS to be a useful prognostic indicator after MVP.

Sinus rhythm maintenance and the changes of echocardiographic parameters in patients with late persistent atrial fibrillation at 6 months after direct current cardioversion

Abstract Background Late persistent non-valvular atrial fibrillation (AF), with a duration of its episode ≥90 days and up to 12 months, is considered a distinct persistent AF entity, which might possess substantial differences as compared to its early persistent pattern (up to 3 months) in terms of myocardial remodeling and its reversibility after cardioversion. Purpose To study the changes of echocardiographic parameters in patients with non-valvular late persistent AF with respect to sinus rhythm (SR) maintenance at 6 months after successful direct current cardioversion (DCCV). Methods The cohort single-center study enrolled 59 late persistent AF patients, who underwent a successful elective DCCV. At 6-months follow-up, patients were subdivided into the groups regarding SR maintenance: 32 (54 %%) patients with a maintained SR (G1), and 27 (46 %) patients with a failure to maintain SR (G2). The parameters of myocardial remodeling and function were evaluated by transthoracic (TTE) and transesophageal echocardiography (TEE) baseline (by TTE and TEE) and at 6-months follow-up (by TTE). Results TTE data from G1 patients, in contrast to G2, suggested better baseline status of left heart chambers, particularly the lower diameter of left atrium (LA), left ventricular (LV) end-diastolic and end-systolic volumes and higher LV systolic function (by LV ejection fraction [EF]). According to the TEE data, G2 (vs. G1) was characterized by more prevalent cases of LA spontaneous (echo) contrast (41 % vs. 15 %, respectively; p=0,042) and LA appendage flow velocity ≤40 cm/s (82 % vs. 53 %, respectively; p=0,022). At 6-months follow-up TTE, G1 patients, as opposed to G2, demonstrated a better profile of echocardiographic parameters, namely a lower LA diameter, LA and right atrium (RA) volumes, along with less advanced LV remodeling and higher LV EF. TTE data from G1 at 6-months follow-up after DCCV suggested the reverse remodeling of both atria, namely the decrease of LA diameter, LA volume and its index (Fig. 1), as well as RA volume and its index. Moreover, G2 demonstrated a decline in LV systolic function, in particular the rise of LV end-systolic volume and decrease of LV EF (Fig. 2), as compared to G1. Furthermore, at 6-months follow-up, G2 patients presented with more advanced severity of PH and tricuspid regurgitation, in comparison with G1. Conclusions Late persistent AF patients with a SR maintenance at 6-months follow-up after successful DCCV presented a better baseline profile of myocardial remodeling and systolic function. The SR maintenance at 6-months follow-up after DCCV was associated with the reverse remodeling of left heart chambers (LA and LV) and RA. On the contrary, a failure to maintain SR in late persistent AF patients was associated with a deterioration in LV systolic function, and more advanced PH and tricuspid regurgitation.