Ventricular Volume Research Articles

Effects of new hypoglycemic drugs on patients with heart failure: a systematic review and network meta-analysis.

Currently, there is no relevant study comparing sodium-dependent glucose transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase inhibitor (DPP4i) head to head to evaluate their comprehensive impact on heart failure patients. We conducted a comprehensive literature search across multiple databases. Utilizing the risk of bias tool from the Cochrane Collaboration, the methodological quality of included studies was critically assessed and potential publication bias was examined via funnel plots. All results are presented as mean difference; 95% confidence interval (MD; 95% CI). The network meta-analysis indicated that in regards to left ventricular function, there is a big difference in the left ventricular ejection fraction (LVEF) of Empagliflozin 25mg (13.64; 0.26, 27.01) compared to Canagliflozin 100mg; and significant differences in the left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) of Dapagliflozin 10mg (-0.76; -1.27, -0.25 and -0.95; -1.86, -0.05), Vildagliptin 50mg (-1.05; -1.47, -0.63 and -1.12; -2.19, -0.05), and Sitagliptin 100mg (-1.34; -2.31, -0.38 and -1.89; -3.50, -0.27) compared to Empagliflozin 10mg. In terms of the quality of life, there are significant differences in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the Quality of life score of Sitagliptin 100mg (408.08; 213.59, 602.57 and 3.74; 1.57, 5.92) compared to Dapagliflozin 5mg. In terms of the cardiovascular outcome events, there is a significant difference in the heart failure rehospitalization rate of Dapagliflozin 10mg (0.45; 0.25, 0.82) and Empagliflozin 10mg (0.48; 0.28, 0.81) compared to Liraglutide 1.8mg. Further significant differences are found in the all-cause mortality of Dapagliflozin 10mg (0.81; 0.66, 0.98) compared to Vildagliptin 50mg; the cardiovascular death of Albiglutide 30mg (0.49; 0.28, 0.86) compared to Exenatide 2mg; and the arrhythmic events of Liraglutide 1.8mg (0.49; 0.26, 0.90) compared to Empagliflozin 10mg. The network meta-analysis of SGLT2i, GLP-1RA, and DPP4i as a class of drugs showed that GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV. GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV. Key message What is already known on this topic-It has been confirmed that three new hypoglycemic drugs have a protective effect on the cardiovascular system. Studies have shown that sodium-dependent glucose transporter 2 inhibitors (SGLT2i) can improve cardiovascular outcomes and enhance the quality of life of heart failure patients. Currently, SGLT2i is widely used in the clinical treatment of heart failure, and related studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase inhibitor (DPP4i) also play important roles in the treatment of heart failure. What this study adds-However, there is no relevant research on whether these drugs' clinical efficacy is dose-dependent. How this study might affect research, practice, or policy-This study included different doses of hypoglycemic drugs and used a network meta-analysis method to comprehensively evaluate the effects of three hypoglycemic drugs on heart function, quality of life, and prognosis in heart failure patients, providing a basis for clinical practice.

Circulating microRNA-409-5p and USP7 are associated with left ventricular remodeling in patients with acute myocardial infarction

BackgroundOur previous study demonstrated that microRNA-409-5p (miR-409-5p) and its target ubiquitin-specific protease 7 (USP7) were involved in hypoxia-induced cardiomyocyte injury and ischemic left ventricular remodeling (LVR) in rats. This study aimed to probe into the relationship between plasma miR-409-5p and USP7 levels and LVR and dysfunction in patients with acute myocardial infarction (AMI).MethodsSixty patients with acute myocardial infarction (AMI) and 60 cases with chronic coronary syndrome (CCS) were enrolled. The clinical characteristics, echocardiographic/serum parameters of LVR, and circulating miR-409-5p and USP7 mRNA levels between the two groups and between admission and 6 weeks after discharge were compared. The correlations between circulating miR-409-5p/USP7 levels and serum/echocardiographic parameters were analyzed.ResultsThe demographic characteristics of the AMI group and CCS group were comparable. Patients with AMI admitted to the study displayed significantly higher levels of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and growth stimulation expressed gene 2 (ST2), along with a greater left ventricular end-systolic volume (LVESV). Conversely, their left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), and global radial strain (GRS) were significantly lower compared to patients with CCS. These changes were normalized 6 weeks after discharge. Circulating miR-409-5p levels at admission were significantly decreased while circulating USP7 mRNA expression levels were significantly increased in patients with AMI compared with those with CCS (both P < 0.01). However, these changes were restored 6 weeks after discharge (both P < 0.01). Moreover, circulating miR-409-5p and USP7 mRNA levels showed varying correlations with GLS, GRS, LVESV, LVEF, and NT-proBNP in patients with AMI but not in those with CCS. Additionally, circulating miR-409-5p and USP7 levels predicted the incidence of LVR and major adverse cardiovascular events (MACE) after AMI.ConclusionSerum miR-409-5p and USP7 may influence the occurrence and evolution of LVR and left ventricular dysfunction after AMI.

Choroid Plexus Volume in Pediatric-Onset Multiple Sclerosis.

Recent studies suggest that the choroid plexus (CP) may function as a site of access of inflammatory cells into the CNS in multiple sclerosis (MS). Pediatric-onset MS (POMS) is characterized by a high inflammatory burden, as evidenced by a high relapse rate and volume of T2 lesions, making patients with POMS an informative population to evaluate choroid plexus volume (CPV). The objectives of the study were (1) to evaluate CPV at symptom onset in participants with POMS compared with healthy controls (HCs); (2) to evaluate changes in CPV in the first year of disease in participants with POMS; and (3) to evaluate associations between CPV, brain volumes, relapse activity, and disability in participants with POMS. Baseline 1.5T MRI scans were acquired from 23 participants with POMS and 23 age-matched and sex-matched HCs; 18 participants with POMS also had 12-month follow-up MRI scans. The CP of the lateral ventricles was segmented manually. CP and brain structure volumes were normalized for total intracranial volume. The number of relapses, T2 and gadolinium-enhancing T1 lesion counts, and Expanded Disability Status Scale (EDSS) scores at 12 months were also analyzed. Baseline CPVs were compared between groups using the Wilcoxon exact test, and CPV change from baseline to 12 months in participants with POMS was compared using the Wilcoxon signed-rank test. The relationship between CPV and brain volumetric measures, T2 lesion volumes, lesion count, number of relapses, and EDSS scores was assessed through Spearman correlation. The median normalized CPV was 1.51 × 10-3 (interquartile range [IQR]: 1.32-1.76) in POMS baseline scans and 1.21 × 10-3 (IQR: 1.1-1.47) in HC scans (p = 0.001). CPV did not significantly change at 12 months in the 18 participants with POMS with follow-up scans (p = 0.352). CPV in participants with POMS and HCs correlated with lateral ventricular volume (p = 0.012 for both groups) but did not correlate with brain and T2 lesion volumes or lesion count at baseline, nor with relapse activity or EDSS scores at 12 months in participants with POMS. CPV measured at baseline is greater in participants with POMS than in HCs. Baseline CPV did not predict higher disease activity or worse neurologic outcomes over 1 year. While higher CPV may be an early feature of inflammation in MS, its strong correlation with ventricular volumes could also reflect enlargement secondary to the mechanical attachment of CP to the ventricular wall.

Three-Dimensional Speckle Tracking Echocardiography Assessment of Right Ventricular Function in Chronic Coronary Syndrome Patients After Percutaneous Coronary Intervention.

This study aimed to assess alterations in right ventricular (RV) function following percutaneous coronary intervention (PCI) in patients with chronic coronary syndromes utilizing three-dimensional speckle tracking echocardiography (3D-STE). A prospective study was conducted involving 136 patients diagnosed with chronic coronary syndromes undergoing PCI, constituting the study group, alongside 110 age- and gender-matched healthy volunteers serving as the control group. Echocardiographic evaluations, including both conventional and three-dimensional assessments, were performed on all study participants at 1-week, 6, and 12 months post-PCI. Parameters such as tricuspid annular plane systolic excursion (TAPSE) were derived from conventional echocardiography, while tricuspid lateral annular systolic velocity (S') was measured via tissue Doppler imaging. 3D-STE was utilized to quantify metrics including right ventricular fractional area change (RVFAC), right ventricular free wall longitudinal strain (RVFWLS), right ventricular global longitudinal strain (RVGLS), right ventricular stroke volume (RVSV), and right ventricular ejection fraction (RVEF). TAPSE, S', RVFAC, RVFWLS, RVGLS, RVSV, and RVEF exhibited significant increases from 1-week to 6 months post-PCI (p < 0.05). However, from 6 to 12 months post-PCI, RVFAC, RVGLS, RVSV, and RVEF demonstrated no notable changes (p > 0.05). Meanwhile, TAPSE, S', and RVFWLS sustained significant elevations: TAPSE (19.63±3.253% to 22.603±2.885%, p < 0.001); S' (10.57±2.643 to 12.61±2.189cm/s, p < 0.001); RVFWLS (18.64±2.745% to 19.926±3.291%, p = 0.002). At 12 months post-PCI, S', RVFAC, RVGLS, RVSV, and RVEF remained lower than those of the healthy control group, but the differences were not statistically significant (p > 0.05). However, RVFWLS was significantly lower compared to the healthy control group (19.926 ± 3.291%vs. 22.10 ± 1.994%, p < 0.001). Following PCI, right ventricular systolic function in patients with chronic coronary syndromes improves significantly over time. However, even at the 12-month post-PCI mark, RVFWLS remains lower than that of the control group. Notably, 3D-STE emerges as a noninvasive method for quantifying right ventricular systolic function post-PCI in chronic coronary syndrome patients.

Cardiovascular magnetic resonance semi-automated threshold-based post-processing of right ventricular volumes in repaired tetralogy of Fallot.

Cardiovascular magnetic resonance (CMR) is the gold-standard to estimate right ventricular (RV) volumes, which are key for clinical management of patients with repaired tetralogy of Fallot (rTOF). Semi-automated threshold-based methods (SAT) have been proposed for CMR post-processing as alternatives to fully manual standard tracing. We investigated the impact of SAT on RV analysis using different thresholds in rTOF patients. RV volumes and mass were estimated using SAT and standard fully manual tracing methods in rTOF patients. Two threshold levels were set for SAT, i.e., default 50 (SAT-50) and 30 (SAT-30). RV stroke volumes (SV) were compared to main pulmonary artery forward flow (MPA-FF). Post-processing time, intra- and interobserver variabilities were compared across methods. Sixty-two CMRs of rTOF patients were analyzed. Compared to the standard fully manual tracing, no significant differences in RV mass, volumes and ejection fraction were observed using SAT-30, whereas SAT-50 significantly underestimated RV end-diastolic-volume index (EDVi) by 10.4% (mean difference of - 11.8 ± 6.2ml/m2, p 0.03) and overestimated RV mass index by 21.8% (mean difference of 14.2 ± 11.9g/m2, p 0.002). Compared to MPA-FF, RVSV by standardfully manual method and SAT-30 showed minor biases, respectively, 0.03ml/m2 and 0.7ml/m2, while SAT-50 underestimated RVSV by 6.86ml/m2 (p < 0.001). In six patients, the degree of RV EDVi underestimation by SAT-50 determined a change of category from dilated to non-dilated RV. Intra- and interobserver variabilities were good to excellent for all methods. Post-processing duration was shorter for SAT compared to standardmanual segmentation (5.5 ± 1.7min vs. 19.5 ± 4.4min, p < 0.001). CMR SAT-30 post-processing is a precise, accurate and time-saving method for biventricular assessment of volumes, ejection fraction and mass in rTOF.

Ebstein's anomaly with coarctation of the aorta and a bicuspid aortic valve: a case report of a rare association with unique prenatal findings.

Ebstein's anomaly is rarely accompanied by coarctation of the aorta, although patients with Ebstein's anomaly have a relatively small left ventricle. Here, we report a rare case of Ebstein's anomaly with coarctation of the aorta and a bicuspid aortic valve. We compared the foetal echocardiographic parameters of five previous cases with Ebstein's anomaly without left heart obstruction to explore the association between left ventricular volume, Ebstein's anomaly severity, and left heart obstruction.

The in-hospital administration of sacubitril/valsartan in acute myocardial infarction: A meta-analysis.

There is a need to address the evidence gap regarding the in-hospital administration of sacubitril/valsartan in acute myocardial infarction patients. After searching MEDLINE, Google Scholars and Scopus, a random-effects meta-analysis of randomized controlled trials comparing the in-hospital administration of the angiotensin receptor-neprilysin inhibitors (ARNis) versus the standard therapy in patients with reduced heart failure due to myocardial infarction was performed. The primary outcome was major adverse cardiovascular events. All-cause mortality, cardiac death, rehospitalization for heart failure, non-fatal myocardial infarction (MI), changes in left ventricular ejection fraction, left ventricular volumes, N terminal pro brain natriuretic peptide and adverse events were the secondary endpoints. Nine studies (eight randomized controlled trials and one echo-substudy) with a total 6597 individuals (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker: 3300 patients vs. ARNis: 3297 patients) were included for quantitative analysis. Median follow-up was 6months. Patients receiving an in-hospital coadministration of ARNi had a lower risk of major cardiovascular event [odds ratio (OR) 0.45, 95% confidence interval (CI) 0.32-0.63, P<0.0001] and lower rate of repeat rehospitalization for heart failure (OR 0.40, 95% CI 0.26-0.62, P<0.0001), compared with a standard regimen. Additionally, left ventricle volumes were significantly lower in the ARNi group [left ventricular end-diastolic volume, mean difference (MD) 11.48mL, 95% CI 6.10-16.85, P<0.0001; left ventricular end-systolic volume, MD 7.09mL, 95% CI 2.89-11.29, P=0.0009] with a significant change in left ventricular ejection fraction (MD 3.07, 95% CI 1.61-4.53, P<0.0001), compared with standard therapy. No significant differences were observed in terms of cardiac death, all cause of mortality, non-fatal myocardial infarction and N terminal pro brain natriuretic peptide. Higher rates of iatrogenic hypotensive events were observed in the ARNi group compared with the standard therapy (OR 1.42, 95% CI 1.26-1.60, P value<0.00001). In patients with acute myocardial infarction related heart failure, the in-hospital administration of ARNis was associated with a reduced risk of major cardiovascular events and re-hospitalization for heart failure, as well as cardiac remodelling, but higher rates of hypotensive events compared with standard therapy.

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

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

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 &amp;lt; 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

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

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

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.

Large sample size MRI measurements to assess the relation between cardiac function and structure and white matter hyperintensity volumes

Abstract Background People with established cardiovascular disease (CVD) are at risk of early cognitive decline, and neurological diseases such as dementia. CVD and neurological diseases share common risk factors, such as blood pressure, sedentary lifestyle, as well as genomic risk factors such as mutations in APOE4 [1]. It's unclear to what extent the co-occurrence of CVD and neurological diseases is explained by these risk factors, or whether there is a direct association where CVD is a first step towards poorer neurological health. White matter hyperintensities (WMH) of presumed vascular origin are damaged areas in the brain observed through magnetic resonance imaging (MRI). These lesions are associated with progressive neurological disease such as vascular dementia, as well with risk factors for CVD [2]. Purpose We set out to determine to what extent CMR measurements associated with WMH independent of known cerebrovascular risk factors. Methods Cardiac and brain MRI images were analysed for 23,963 UK biobank (UKB) participants. WMH analysis included 5 brain regions (Frontal[F], Parietal[P], Temporal[T], Occipital[O], Basal Ganglia and Thalami [BGT]) and total brain WMH volume. Cardiac traits included stroke volumes, atrial volumes, ejection fractions of right and left chambers, left ventricular (LV) strain, LV wall thickness and aortic areas. Multivariable regression analysis was carried out, where each cardiac trait was regressed on each brain region and adjusted for: age, difference between age at initial visit and imaging visit, sex, systolic and diastolic blood pressure, Hba1c, household income, educational status, Townsend score and family history of disease (Alzheimer’s, Parkinson's, high blood pressure, stroke, heart disease) . Results were evaluated against a multiple testing correct p-value threshold of 0.05, reflecting the number of principle components(n=10) necessary to explain 90% of the cardiac trait variability. Results For 5 cardiac traits (right ventricular stroke volume, left atrial stroke volume, left ventricular stroke volume, left ventricular ejection fraction and right ventricular end diastolic volume) higher values were associated with lower WMH volumes in all brain regions. Additionally, some cardiac traits such as LV cardiac output associated with specific brain regions (T, O, BGT). Additionally, APOE- ε4 stratified analyses indicated, homozygous carriers show a greater association between higher minimum LA and RA volumes and higher WMH volumes in the occipital lobe. Conclusions This study gives an insight into the WMH burden in a large population of adults. It highlights the associations of cardiac traits with white matter hyperintensity volumes in different brain regions independent of known risk factors. Using cardiac traits as surrogate markers of different cardiac disease could explain how cardiac functionality defines WMH volume distribution and subsequently the wider relationship between CVD and cerebrovascular disease.Figure 1Graphical Abstract

Larger QRS but better hemodynamic function after high output His bundle pacing in patients with heart failure and narrow QRS. A paradox or a new concept?

Abstract Background QRS duration is an important factor in determining Cardiac Resynchronisation Therapy (CRT) response and a useful surrogate for electromechanical dyssynchrony. However, we don’t have studies confirming this concept in conduction system pacing. Purpose We performed His Bundle Pacing (HBP) with high output (3.5V/1msec) in HF patients with dilated or ischemic cardiomyopathy and narrow QRS to evaluate hemodynamic benefit independent of the QRS duration or AV delay shortening. Methods 14 patients with dilated (7 patients) or ischemic (7 patients) cardiomyopathy (EF&amp;lt;35%) and narrow QRS (&amp;lt;120ms) were referred for implantation of a defibrillator. We implanted an ICD- HBP system, and we collected clinical, echocardiographic, and electrocardiographic data. Results We obtained HBP in all 14 patients successfully. PQ after implantation was shorter from 172±48 to 143±16 (P=0.048) so as to pace the ventricle. Baseline QRS duration increased after pacing from 110±15 to 123±16ms (P=0.008) as measured by ECG analyzer. Despite this increase in QRS duration basal mean EF increased from 30±4% to 46±10% (P&amp;lt;0.001) after a median follow-up of 17 months. Left ventricular end-diastolic diameter and left ventricular end-diastolic volume decreased from 62±5 to 57±5mm (P=0.013) and from 195±69 to 126±27ml (P&amp;lt;0.001), respectively. Left ventricular end-systolic volume decreased from 139±58 to 69±27 (P&amp;lt;0.001). TAPSE increased from 19±4 to 27±4. NYHA class decreased by one class in every patient after only one month. HBP threshold was 1.05V±0.7/1msec and raised to 1.33±0.93/1msec (due mainly to 2 patients with very high threshold). The impedance was 588±109 and decreased to 484±69 Ohms. R-wave at implant was 3.2±1.8mV. In 2 out of 14 patients, threshold increased but was still less than 3.5V/1msec. Conclusions HBP in HF patients with dilated or ischemic cardiomyopathy and narrow QRS improves hemodynamic function in right and left ventricle and decreases NYHA class. This benefit appears to be produced by a higher stimulation output despite a larger QRS after pacing. We exclude that a very short AV delay could be favorable, by measuring acute EF changes only after increasing the pacing output without AV delay modifications. To our knowledge these are the first cases of beneficial HBP in HF patients with narrow QRS. Interestingly, larger QRS corresponds to higher EF in patients with high output HIs Bundle Pacing.

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&amp;lt;.001 for cluster 2; 95% CI 1.49-2.78, p&amp;lt;.001 for cluster 3; 95% CI 1.92-3.62, p&amp;lt;.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.

Myocardial parametric mapping in patients with suspected acute myocarditis: a prognosis study

Abstract Background T1 mapping and T2 mapping have become essential components of the 2018 Lake Louise criteria and obtained excellent results in diagnosing myocarditis. However, their prognostic value in acute myocarditis has not yet been well recognized or established. Purpose Our study aims to investigate the prognostic value of T1 mapping, T2 mapping, and extracellular volume fraction (ECV) in a large cohort of patients with suspected acute myocarditis. Materials Patients meeting the recommended clinical criteria for suspected acute myocarditis were consecutively enrolled. The primary endpoint is the composite of cardiac death, heart failure hospitalization, heart transplantation, sustained ventricular arrhythmia, and recurrent myocarditis, defined as major adverse cardiovascular events (MACE). All patients underwent CMR at 3.0 T scanner using a standardized, routine imaging protocol, and the three short-axis view slices (basal, mid-ventricular, and apical) were divided into 16 segments according to the American Heart Association 17-segment model (apex excluded). We also averaged the native T1 values, ECV, and T2 values of all 16 segments to get global T1 and ECV fraction values, respectively. Statistically significant parameters from univariate Cox analyses were put into multivariate Cox analysis. Results A total of 235 patients (150 men; 32±13 years) were enrolled in this study. During a mean follow-up of 43.0±3.6 months, MACE occurred in 37 patients (15.7%) and was univariably associated with heart failure presentation, left ventricular ejection fraction, left ventricular end-systolic volume index, left ventricular end-diastolic volume index, native T1 and ECV. Patients with MACE showed higher global native T1, ECV, and T2 values (1348±59 vs 1266±51, p=&amp;lt;0.001; 40.0±8.7 vs 32.8±5.9, p&amp;lt;0.001; 63.4±12.1 vs. 55.5±9.1, p=0.011), and were more likely to have tissue changes in the interventricular septum and anterior wall (Figure 1). In a series of nesting multivariable Cox regression models, the addition of native T1 (per 10-ms increase: HR, 1.128; 95% CI: 1.043, 1.220; p = 0.003; Harrell’s C-index = 0.833) or ECV (per 5% increase: HR, 1.382; 95% CI: 1.060, 1.802; p = 0.017; Harrell’s C-index = 0.847) improved prognostication compared with the model based on clinical variables, left ventricular ejection fraction, and septal late gadolinium enhancement (Harrell’s C-index = 0.762) (Figure 2). T2 in multivariate Cox regression analysis didn’t show predictive value, but his inclusion increased the C-index of the model to 0.814. Conclusions Myocardial parametric mapping not only holds substantial diagnostic value but also plays a critical role in the prognostic assessment and risk prediction of myocarditis. Their utilization in these contexts enhances the accuracy and effectiveness of clinical evaluations and decision-making processes.

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&amp;lt;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&amp;lt;0.001), and take cholesterol medication (72.3% vs 27.2%, p&amp;lt;0.001); anti-hypertensives (56.3% vs 27.3%, p&amp;lt;0.001); insulin (13.7% vs 0.1%, p&amp;lt;0.001); and metformin (53.1% vs 0.1%, p&amp;lt;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 &amp;gt;0.3 or &amp;lt;-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&amp;lt;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.

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

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

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

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

Multi-biomarker approach for predicting cardiac magnetic resonance parameters at 30 days after ST-segment elevation myocardial infarction

Abstract Background Prior data showed associations of circulating Proprotein Convertase Subtilisin / Kexin type 9 (PCSK9) and inflammatory/anti-fibrotic Cellular Communication Network factor 1 (CCN1) at index ST-segment elevation acute myocardial infarction (STEMI) with left ventricular ejection fraction at 6 and 12 months, respectively and for CCN1 also with infarct size. Purpose PCSK-9, CCN1 and reference biomarkers high-sensitivity Troponin T (hsTNT) and N-terminal pro-brain natriuretic peptide (NTproBNP) were measured in patients from the CLEVER-ACS trial (clinicaltrials.gov NCT01529554) at presentation with STEMI and correlated with clinically relevant cardiac magnetic resonance (CMR) parameters at 30 days. Methods Associations between baseline biomarkers (PCSK-9, CCN1, hsTNT, NTproBNP) and CMR parameters at 30 days were evaluated using Spearman correlation and linear regression analysis (dichotomised at their median). Receiver operating characteristic (ROC) and area under the curve (AUC) were determined for significant values based on correlation analysis; AUC &amp;gt; 0,7 considered relevant. CMR parameters comprised left ventricular structural and functional parameters including scar mass and microvascular obstruction. Results We identified 56 STEMI patients (mean age 61.7 ± 11.2 (SD) years) who completed 30 days follow-up with biomarker data. Among biomarkers, significant associations with CMR parameters were only found for hsTNT, and NTproBNP. The strongest associations were found for left ventricular ejection fraction (LVEF; hsTNT RSp =-0.66; NTproBNP RSp =-0.57), left ventricular scar (LVSCAR; hsTNT RSp =0.58; NTproBNP RSp =0.56) and scar mass (SM; hsTNT RSp =0.65; NTproBNP RSp =0.55). Conversely, left ventricular end-diastolic volume index (LVEDVI; hsTNT RSp =0.47; NTproBNP RSp =0.32), left ventricular end-systolic volume index (LVESVI; hsTNT RSp =0.51; NTproBNP RSp =0.39) and microvascular obstruction (MVO; hsTNT RSp =0.34; NTproBNP RSp =0.34) were significantly, albeit only modestly associated. ROC and AUC analysis yielded relevant associations of biomarkers with CMR parameters LVEF (hsTNT=0.79; NTproBNP=0.81), LVSCAR (hsTNT=0.84; NTproBNP=0.76) and scar mass (hsTNT=0.83; NTproBNP=0.78). Furthermore, relevant associations of biomarkers with CMR were found for LVEDVI (hsTNT=0.79; NTproBNP=0.72), LVESVI (hsTNT=0.84; NTproBNP=0.72) and MVO (hsTNT=0.72; NTproBNP=0.71). Conclusion Baseline levels of hsTNT and NT-proBNP are strong predictors for functional and dimensional CMR parameters of the left ventricle including clinically relevant imaging surrogates of myocardial injury shortly after STEMI.ROC LVEF

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&amp;lt;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&amp;lt;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.