Ventricular Strain Research Articles

Effects of Dapagliflozin on myocardial performance in non-diabetic patients with Heart failure with reduced and mid-range ejection fraction (DAPA ECHO trial)

Abstract Background Sodium-glucose cotransporter type-2 inhibitors (SGLT2i) showed to reduced morbidity andmortality in HF patients. The aim of this study was to assess potential effects of dapagliflozin in non-diabetic patients with heart failure (HF) with reduced and mildly reduced ejection fraction (HFrEF and HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE). Methods This randomized, prospective, single-center, open-label trial compared consecutive non-diabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except SGLT2i (Fig.1). Primary endpoint was the modification of left ventricular (LV) global longitudinal strain (GLS), diastolic function (as peak atrial longitudinal strain, PALS) and right ventricular (RV) function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints. Results Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n=44) or to continue with OMT (n=44). All STE values improved in dapagliflozin group after 6 months, while there was a non-significant improvement in OMT group (Fig.1). Moreover, when comparing the modification of STE parameters at follow up in HFrEF and HFmrEF patients, only the main treatment effect resulted statistically significant in both groups (p<0.0001), indicating a significant difference between dapagliflozin and OMT. Conclusions This study provided randomized data on the beneficial effect of dapagliflozin in non-diabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique i.e. STE. This suggests its usefulness for LV reverse remodeling and better quality of life in patients with HFrEF and HFmrEF.

Speckle tracking echocardiography for evaluation of myocardial functions before and after mitral valvuloplasty in dogs

BackgroundMyxomatous mitral valve disease (MMVD) is the most common acquired heart disease in dogs. Mitral valvuloplasty (MVP) addresses regurgitation, but the pre- and postoperative changes in myocardial function remain uncertain.ObjectivesThis study evaluated myocardial motion before and after MVP using two-dimensional speckle-tracking echocardiography (2D-STE).AnimalsEight client-owned dogs undergoing MVP for MMVD.MethodsMyocardial deformation was assessed by 2D-STE before surgery and at 1- and 3-months post-surgery. Measurements included left ventricular global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), cardiac twist, and right ventricular free wall GLS (RVFW-GLS).ResultsPostoperative decreases were observed in left ventricular internal dimensions, left atrial size, and early diastolic myocardial velocity, with an increase in peak late diastolic velocity. LV-GLS decreased at 1 month (−14.4%) and 3 months (−16.3%) compared to preoperative values (−24.4%) (p = 0.0078, p = 0.015). GCS decreased at 1 month (−12.9%) and 3 months (−14.8%) compared to preoperative values (−21.7%) (p = 0.0078). GRS decreased at 1 month (27.7%) and 3 months (32.0%) compared to preoperative values (67.7%) (p = 0.0078). No significant changes were observed in RVFW-GLS. Peak systolic twist increased at 3 months (9.1° vs. 4.9°, p = 0.039). Peak systolic apical rotation showed an upward trend at 3 months (p = 0.109). Left ventricular twist was mildly affected by LVIDd, LVIDDN, and sphericity index (R2 = 0.187, p = 0.034; R2 = 0.33, p = 0.0029; R2 = 0.22, p = 0.019).Conclusions and clinical importancePostoperative myocardial motion approached reference values, indicating significant improvement, particularly in left ventricular twisting motion. These findings highlight the positive impact of surgery on cardiac function in dogs with MMVD.

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

The left ventricular strain-volume loop in a healthy Dutch population: age- and sex related differences

Abstract Introduction By combining left ventricular (LV) global longitudinal strain (GLS) with LV volume during the cardiac cycle, LV strain-volume loops can be generated. LV SV-loop derived parameters provide new insights into the interaction between cardiac contraction and volume in a variety of cardiac diseases (1,2) and may even have prognostic value. (3,4) Reference values for healthy individuals with attention to sex- and age-related differences have not been established yet. Therefore, the aim of this study is to provide reference ranges in a healthy adult population and investigate potential sex- and age-related differences of LV SV-loop characteristics. Methods In 125 healthy volunteers aged 18-72 years, apical 2-, 3- and 4-chamber views were acquired to measure GLS. Custom software was used to combine strain and volume data to construct SV-loops. Different parameters were derived: (i)linear slope of systolic strain-volume relation (S-Slope); (ii) early linear slope of systolic strain-volume relation (ES-Slope); (iii) early linear slope of diastolic strain-volume relation (ED-Slope); and (iv) uncoupling between systolic and diastolic strain-volume relation (UNCOUP). Results For the systolic strain-volume relation higher values were observed in females as compared with males with S-Slope values of 0.19 [0.17-0.22] %/mL m-² and 0.13 [0.11-0.15] %/mL m-² respectively. ED-Slope was higher in females as compared with males with values of 0.18 [0.09-0.28] %/mL m-² and 0.12 [0.06-0.18] %/mL m-² respectively. Relative coupling of the systolic and diastolic strain-volume relation was observed with a mean value of 0.34 ± 1.1. UNCOUP was correlated with age with a value for r of 0.4. Conclusion Higher values for the systolic and early-diastolic strain-volume relation in females can be reflective of different cardiomechanics as LV contraction is not only comprised of longitudinal but also circumferential and radial deformation. In line with current literature our custom software found relative coupling of the systolic and diastolic strain-volume relation in our cohort of healthy subjects. Towards older age relative uncoupling of the systolic and diastolic strain-volume relation was found.Figure 1.Strain-volume loop

Assessment of a new index of myocardial strain for the diagnosis of cardiac sarcoidosis

Abstract Background The diagnosis of cardiac involvement in sarcoidosis is challenging and often expensive. Purpose The aim of this study is to assess whether a new strain index proposed by the authors has incremental value in the evaluation of cardiac involvement, compared to the use of left ventricular (LV) global longitudinal strain (GLS). Methods This is a single-center, non-blinded, pilot cross-sectional study. Patients of both genders, >18 years old, with confirmed diagnosis of cardiac sarcoidosis according to the Heart Rhythm Society criteria, and controls consisting of individuals diagnosed with systemic sarcoidosis without cardiac involvement, were included. Patients with obesity grade 2 or higher , moderate or severe primary heart valve disease, myocardial diseases of other etiologies, established coronary artery disease, and inadequate acoustic window were excluded. All patients underwent transthoracic echocardiography, with subsequent measurements performed on a workstation. The following LV indexes were evaluated: GLS and the new proposed index, calculated by the ratio between LVEF and the sum of the two segments with the lowest absolute strain values. ROC curves were calculated for both parameters using an online dedicated software, with determination of the optimal cutoff point for both variables, corresponding to the point of highest sensitivity and specificity. Confidence intervals were established by the DeLong method, and curves were compared using the Bonferroni method. A two-tailed p value of 0.05 was considered significant. Results Twenty patients with cardiac involvement and twenty patients without cardiac involvement were evaluated. The results of the variables are presented in table 1. Conclusions The new index showed a larger area under the curve compared to isolated GLS, as well as higher sensitivity and specificity for the identified cutoff point, although without statistical significance, possibly due to the small sample size. Further studies are needed for subsequent validation of this innovative index.

The relationship between coronary microvascular dysfunction and left ventricular longitudinal systolic function in patients with diabetes mellitus

Abstract Background Coronary microvascular dysfunction (CMD) often accompanies diabetes mellitus (DM), leading to myocardial ischemia despite normal or mildly narrowed coronary arteries (<50% stenosis). CMD causes myocardial hypoperfusion, resulting in impaired systolic function. Coronary flow reserve (CFR) serves as a marker of microvascular function, particularly in the absence of significant epicardial coronary stenosis. Myocardial contrast echocardiography (MCE) is a key tool for clinically assessing CFR. Global longitudinal strain (GLS) derived from two-dimensional speckle tracking echocardiography (2D-STE) offers early insights into left ventricular systolic dysfunction during subclinical stages but is underexplored in diabetic CMD patients. Objective This study aimed to assess myocardial microcirculatory dysfunction in diabetic patients using stress myocardial ultrasound enhancement imaging, investigate its relationship with left ventricular longitudinal systolic function, and evaluate the utility of 2D-STE in assessing left ventricular systolic function in CMD patients. The findings provide insights for early detection and prevention of left ventricular longitudinal systolic dysfunction in diabetic patients with myocardial microcirculatorydysfunction. Methods Seventy type 2 diabetic patients who underwent coronary CT or angiography within the past three months without obstructive coronary artery disease were included. Clinical data, biochemical parameters, and blood glucose levels were collected. Left ventricular longitudinal strain indices were obtained using 2D-STE, and microvascular function was assessed based on CFR measured via transthoracic stress MCE. Patients were categorized into CMD (CFR<2) and control (CFR≧2) groups, with clinical and echocardiographic parameters compared. Strain parameters included GLS at rest, GLS under stress, and ∆GLS. Correlations between these indices and CFR were analyzed. Results 1. Seventy patients, with 41 males (41.4%) and 58 females (58.6%), averaging 56.14±10.84 years, were included. The mean BMI was 25.53±3.40. Among them, 23 patients were smokers (32.8%), 41 had hypertension (58.6%), and 36 had hyperlipidemia (51.4%). 2. Patients in the CMD group had significantly shorter diabetes duration (6.59±2.18 years vs. 8.13±2.17 years) and lower glycosylated hemoglobin (7.99±1.52% vs. 8.78±1.55%) (P<0.05). No significant differences were observed in other parameters. 3. GLS and ∆GLS differed significantly between groups, while other echocardiographic parameters did not. 4. Logistic regression analysis identified GLS as an independent predictor of CMD in diabetic patients under stress. Conclusions 1. Diabetic patients with CMD exhibit lower GLS and ∆GLS under stress, indicating early reductions in left ventricular systolic function reserve. 2. 2D-STE can detect early left ventricular systolic impairment in diabetic patients.MCE quantitative analysisGLS in normal and CMD group

Prognostic significance of right ventricular dysfunction in patients with TTR amyloidosis

Abstract Background Transthyretin amyloidosis (ATTR) is increasingly recognized as a cause of heart failure (HF) that now benefits from effective treatment. While the role of right ventricular (RV) systolic dysfunction has been widely accepted as an independent predictor of poor prognosis in HF patients, its implications in ATTR remain poorly understood. Right ventricular free wall strain (FWS) over pulmonary arterial systolic pressure (PAsP) has been recently proposed as an accurate and sensitive tool to evaluate RV function and its coupling to the afterload. Purpose Our study sought to analyze whether indexing FWS to PASP should integrate the set of fundamental data we have to assess the prognosis of ATTR patients. Methods 191 consecutive patients diagnosed with ATTR were enrolled. A comprehensive echocardiographic examination was part of the systematic evaluation. The primary outcome was a composite of cardiovascular mortality and hospitalization caused by heart failure worsening. Results After a median follow-up of 24 months, among patients with ATTR [median age 82 (77, 85), 89.5% male], the primary composite outcome occured in 26%. Cardiovascular mortality rate was 7.3% and the hospital event rate was 18.8%. Tricuspid annular plane systolic excursion (TAPSE), FWS, TAPSE/PAsP and PAsP were univariately significant risk factors for adverse outcome. In multivariate Cox regression analysis, after adjustment of confounding factors, FWS/PASP emerged as an independent predictor of the composite endpoint of cardiac death and rehospitalization (HR 1.61, 95% CI 1.07-2.42, p=0.021). Based on receiver-operating characteristic analysis, the optimal FWS/PASP cut-off value for event prediction was 42.5% (area under the curve = 0.749, p = 0.001). Conclusion Right ventricular function assessed with speckle-tracking echocardiography is an independent prognostic marker for cardiac mortality and heart failure hospitalization in patients with ATTR. FWS/PAsP should be integrated into regular clinical practice for a better evaluation and follow-up of ATTR patients.

Improving time-efficiency and accuracy in echocardiography: real-time automated measurements of left ventricular global longitudinal strain using deep learning

Abstract Background Accurate quantification of left ventricular (LV) systolic function is fundamental in echocardiography. LV Global Longitudinal Strain (GLS) offers advantages over LV ejection fraction, being more sensitive, reproducible and offering better prognostic value. However, existing semi-automatic methods are time-consuming and heavily operator-dependent. Additionally, poor image quality and foreshortening decrease accuracy and reproducibility of GLS. As a result, these challenges lead to suboptimal efficiency and underutilization of GLS quantification in clinical practice. Purpose Our objective was to develop a deep learning (DL) application for real-time automated measurements of GLS, capable of providing tracking quality and foreshortening feedback during scanning. Subsequently, we aimed to validate the novel method in a prospective cohort study. Methods Deep learning networks were trained to identify apical views, identify timing of end-systole and end-diastole, conduct cardiac segmentation, estimate myocardial motion, assess LV length in each view for foreshortening detection, and present real-time visualization of tracking quality and GLS values for three cardiac cycles to the operator for review (Figure 1). The DL method was validated in a prospective cohort of 40 patients included regardless of image quality. Agreement with manual measurements obtained using semi-automatic software (EchoPAC version 204, GE HealthCare, Horten, Norway) was evaluated. Bland-Altman statistics and Pearson's correlation coefficient were used to evaluate agreement and correlation. Results Feasibility for real-time DL measurements of GLS was 98%, with one patient excluded due to poor image quality. There was good agreement (Bias 0.7%, LoA: -1.6 to 3.1%, figure 2) and excellent correlation (Pearson’s correlation coefficient of 0.93, p<0.001) between the real-time DL application and manual reference measurements for GLS. Using the DL application during scanning resulted in a 58% (95% CI 56%-61%) reduction in time required for scanning and post-processing to obtain GLS values, compared to using the semi-automatic method. Average time consumption was 2 minutes and 16 seconds for the DL method and 5 minutes and 27 seconds for the reference method. Conclusion Using deep learning, real-time fully automated measurement of GLS during scanning is feasible, time-saving, and provides good agreement with reference methods. Real-time measurements also offer the potential to reduce operator-related variability by integrating tools to provide image and tracking quality feedback to the user, ultimately benefiting patients.Application user interfaceAgreement between DL and reference

Twelve-months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with type 1 diabetes mellitus

Abstract Background Individuals diagnosed with type 1 diabetes mellitus (T1DM) exhibit indications of vascular and endothelial dysfunction earlier in comparison to healthy individuals. Evidence shows that SGLT-2 inhibitors (SGLT-2i) have a beneficial impact on cardiovascular health in individuals with type 2 diabetes mellitus (T2DM). We investigated the effects of dapagliflozin on endothelial and cardiovascular function in patients with T1DM. Methods We recruited in total 40 patients with T1DM and pour glycemic control who were treated with insulin and received dapagliflozin (n=20) or intensification of insulin treatment (n=20) (control group). We measured at baseline and at twelve months post-treatment the: a) Carotid-femoral pulse wave velocity (PWV-Complior; ALAM Medical) b) Central systolic blood pressure (cSBP) c) Perfused boundary region (PBR) of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness) and d) Left ventricular global longitudinal strain (GLS) using speckle-tracking echocardiography. Results At baseline, patients among the two groups had similar age, sex, HbA1c and markers of endothelial and cardiovascular function (p>0.05). After 12 months of treatment, patients who received dapagliflozin displayed an improvement in PBR5–25 (−16%, p<0.05), in PWV (−9.3%, p<0.05), in cSBP (−6%, p<0.05) and in GLS (+4%, P<0.05) compared to baseline. However, no statistically significant changes in PBR5–25, in PWV, in cSBP and in GLS were observed after intensification of insulin treatment (PBR5–25: +0.4%, PWV: -1%, cSBP: −2%, GLS: −1% at 4 months, P>0.05), despite a similar HbA1c reduction (Table 1). Changes of PBR after one year treatment with dapagliflozin correlated with a concomitant reduction of PWV and cSBP (P<0.05). Conclusions Twelve months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with T1DM, independently of glycemic control.

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

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

Association of visceral adipose tissue with echocardiographic abnormalities in type 2 diabetes patients

Abstract Introduction Ectopic deposition of adipose tissue, particularly visceral adipose tissue (VAT) has been identified as a significant contributor to cardiometabolic complications among individuals with type 2 diabetes (T2D). An increase in VAT has been suggested to cause cardiac dysfunction, which may lead to echocardiographic abnormalities such as alterations in speckle-tracking and left ventricular ejection fraction (LVEF). However, this relationship has not been fully elucidated. Purpose This study aims to determine the association between VAT and echocardiographic abnormalities in patients with T2D. Methods A cross-sectional study in a tertiary hospital which included 195 individuals with T2D, the diagnosis of autoimmune diabetes was excluded. VAT was measured using electrical bioimpedance (BIA), and cardiac function was determined using echocardiography. A Spearman rank correlation analysis was conducted to evaluate the association between VAT and echocardiographic parameters, with significance set at p < 0.05. Results Within our cohort, the median age was 57 years, with 37% men. Based on the third quartile (P75) cutoff (5 liters for men, 3.75 liters for women), the population was categorized into P1-75 and P75-100 (Table). There were significant differences in LVEF (61% in P1-75 vs. 58% in P75-100, p = 0.041), left ventricular global longitudinal strain (LV GLS) (P1-75: -20.3%, P75-100: -19.2%, p = 0.012), and conduit phase of left atrial strain (LAScd) (P1-75: 25%, P75-100: 20%, p = 0.046). Positive correlations (Figure) were observed between VAT and indexed LV mass (r = 0.171, p = 0.020), basal diameter of the right ventricle (r = 0.308, p = 0.001), and LV GLS (r = 0.197, p = 0.006). Additionally, negative correlations were observed between VAT and LVEF (r = -0.342, p = <0.001) and right ventricular fractional area change (r = - 0.227, p= 0.001). Conclusion Increased VAT was associated with cardiac dysfunction, as indicated by altered LV GLS and LAScd. This study underscores the relevance of VAT in influencing both functional and structural changes in the left and right ventricles. It also highlights the significance of monitoring VAT for comprehensive cardiovascular risk assessment in T2D patients.Clinical demographics tableScatter plots with correlation graphs

Cardiac structure and function in people with cystic fibrosis

Abstract Background Cystic fibrosis (CF) is an autosomal recessive disease affecting multiple organs, however the extent of cardiac involvement in CF is yet to be determined. The remarkable therapeutic advancements with new highly effective CF transmembrane conductance regulator (CFTR) modulator treatment and subsequent increase in life expectancy substantiates further research. Purpose We aimed to explore the prevalence of abnormalities and potential subclinical alterations in cardiac structure and function in adults with CF compared to matched controls and investigate potential cardiovascular risk factors in people with CF (pwCF). Methods In this cross-sectional study, 104 adult pwCF in Denmark underwent clinical and echocardiographic examination. All participants were matched 1:1 with controls from the general population on age and sex. Uni- and multivariable linear regression models with adjustment for heart rate, FEV1, smoking status, hypertension and CF-related diabetes (CFRD) were used to test for differences in echocardiographic parameters between cases and controls. Abnormal cardiac function was defined as left ventricular ejection fraction (LVEF) <50%, left ventricular (LV) global longitudinal strain (GLS) < 16% or presence of diastolic dysfunction. Uni- and multivariable logistic regression models adjusted for age, sex, homozygous genotype, FEV1/FVC, BMI, smoking status, CFRD, pancreatic insufficiency, hypertension, and ischemic heart disease were performed to assess associations between potential risk factors and cardiac dysfunction in CF. Forest plots were constructed to visually represent the findings. Results Of 104 pwCF, 44% were female, mean age was 34 years, 93% received CFTR modulator treatment, and 91% had mutations with only minimal CFTR function (mutation class I-III). The prevalence of abnormal cardiac function in pwCF was 44% versus 22% in controls. Compared to controls, pwCF were found to have smaller LV dimensions, worse LV diastolic function, and more impaired right ventricle (RV) as well as LV systolic function (Table). After multivariable adjustment, LV diastolic function as well as LV and RV systolic function remained impaired in pwCF as compared to controls. Male sex and decreasing FEV1/FVC ratio remained independently associated with abnormal cardiac function in pwCF (male sex: OR 3.94 (1.56; 9.95), p=0.004 and FEV1/FVC ratio: OR 2.05 per 0.1 unit decrease (1.21; 3.52), p=0.008, respectively) (Figure). Conclusion Both left- and right-sided cardiac alterations were found in pwCF. After adjustments for potential risk factors, both RV and LV systolic measures remained altered in pwCF, compared to controls. Male sex and decreasing pulmonary function evaluated by FEV1/FVC-ratio were identified as factors associated with abnormal cardiac function in pwCF.Figure

Evaluation of myocardial work indexes in patients with cardiac sarcoidosis

Abstract Background Cardiac involvement is associated with worse prognosis and mortality in sarcoidosis. Diagnosis often requires expensive and less available tests. Purpose The aim of this study is to evaluate whether non-invasive measurement of myocardial work by transthoracic echocardiogram has incremental value in the diagnosis of cardiac involvement compared to left ventricular (LV) global longitudinal strain (GLS). Methods This is a cross-sectional, non-blinded, single-center pilot study. Patients of both genders > 18 years old, with confirmed diagnosis of cardiac sarcoidosis according to the Heart Rhythm Society criteria, and controls consisting of individuals diagnosed with systemic sarcoidosis without cardiac involvement, were included. Patients with obesity grade 2 or higher , moderate or severe primary heart valve disease, myocardial diseases of other etiologies, established coronary artery disease, and inadequate acoustic window were excluded. All patients underwent transthoracic echocardiography and non-invasive blood pressure measurement, followed by subsequent analysis involving the construction of a pression-strain curve. The following LV indexes were calculated: GLS, global work index, global constructive work, global wasted work, and global work efficiency. ROC curves were calculated for all variables using the EasyROC online tool (v 1.3.1), and these were later compared to GLS. Confidence intervals were established by the DeLong method, and curves were compared by the Bonferroni method. A two-tailed p value of 0.05 was considered significant. Results Twenty patients with cardiac involvement and twenty patients without cardiac involvement were evaluated. The results of the variables are presented in table 1. Conclusions With exception of wasted work, all other LV myocardial work variables showed statistical correlation with cardiac involvement in sarcoidosis patients. However, there was no incremental value of myocardial work indexes compared to the isolated use of GLS.

Differential echocardiographic profiles in immunoglobulin light chain and transthyretin amyloid cardiomyopathy: insights from speckle tracking analysis

Abstract Background Amyloid cardiomyopathy is mainly caused by two main subtypes of amyloidosis; immunoglobulin light chains cardiomyopathy (AL-CM) and transthyretin cardiomyopathy (TTR-CM). Purposes The aim of the present study was to elucidate the differences in echocardiographic findings between AL-CM and TTR-CM using speckle tracking echocardiography. Methods The study included patients with a confirmed diagnosis of cardiac amyloidosis through cardiac biopsy and who underwent transthoracic echocardiography between March 2013 and October 2022. The relative apical sparing index (RASI) was calculated using speckle tracking echocardiography: mean apical strain value/(mean basal strain value + mean mid strain value). Results The final study population consisted of 50 patients with a confirmed diagnosis of cardiac amyloidosis diagnosed pathologically (AL-CM: 21 patients, TTR-CM: 29 patients). Mean age was 72 ± 11 years, 70% being male. AL-CM exhibited a lower left ventricular mass index compared to TTR-CM (124.5 ± 48.9 vs. 152.2 ± 39.2 g/m2, P = 0.001). In 35 patients available with longitudinal strain analysis, no significant difference was observed in left ventricular global longitudinal strain between the two subgroups (-9.9 ± 4.8 vs. -9.3 ± 2.4% , P = 0.63). However, RASI was significantly lower in AL-CM compared to TTR-CM as shown in Figure (0.92 ± 0.29 vs. 1.46 ± 0.53, P = 0.001). Receiver operating characteristic curve analysis shows a RASI cut-off value of <1.0 proved useful in differentiating the diagnosis of AL-CM from TTR-CM (sensitivity: 81%, specificity: 70%, AUC:0.82), and RASI <1.0 remained a significant association with the diagnosis of AL-CM, even after adjusted by conventional echocardiographic variables. Conclusion Apical sparing phenomenon was more remarkable in TTR-CM compared with AL-CM, although global longitudinal strain was comparable between the two groups. RASI was useful for the discrimination of cardiac amyloidosis subtypes.

Echocaridographic assessment of pulmonary hypertension: improving the probability

Abstract Introduction Pulmonary hypertension (PH) is a cardio-pulmonary disorder characterised by raised pulmonary artery pressure (mPAP >20mmHg) leading to right ventricular failure, and death if left untreated. Transthoracic echocardiography (TTE) assessment of PH uses a probability-based approach, combining peak tricuspid regurgitant velocity with other supporting signs. We evaluated the latest ESC TTE PH guidelines in a real-world UK dataset and identified markers that may improve the sensitivity of the existing algorithm. Method Retrospective analysis of 447 patients referred for initial PH assessment. This was a select population of patients who underwent both TTE and right heart catheter (RHC) (mean time to RHC = 40±30 days). In addition to current TTE PH probability markers we analysed right ventricular free wall strain (RVFWS). Measurements were made by a single operator using Tomtec Arena 2020. Crosstabulation, ROC curve analysis and T-tests were used to compare variables between PH and no PH. Results Mean sample age was 64±15 yrs (61% female). 6.9% (n=4) of the no PH group had pulmonary mid-systolic notching, which may be due to pseudo-notching attributable to incomplete Doppler envelope. Sensitivity and specificity of current ESC TTE probability guidelines were 83%, and 65% respectively (95% C.I.). However, within the low probability group (i.e. those felt to be less likely to have PH) 62% (n=63) had confirmed PH at RHC (mPAP = 28±9). The addition of RVFWS as an additional marker to the existing supporting signs of PH (Table 1) resulted in an improvement of the sensitivity of the algorithm to 92% with a mild reduction in specificity (63%). The number of false negatives were reduced by 51%. Of these, the majority were in the low TTE probability group (n = 32). Conclusions Using current PH TTE probability algorithms classifies a significant proportion of those with PH as having a low TTE PH probability. The addition of RVFWS improves the sensitivity of the existing algorithm to 92% and reduces false negatives by 51%.

Right atrial and ventricular function in risk stratification of patients with pulmonary artery hypertension

Abstract Background Right atrial (RA) phasic function was proved to be impaired in individuals with pulmonary arterial hypertension (PAH), the awareness of the nonnegligible involvement of RA in the clinical course of PAH was raised. However, evidence for the clinical significance of the RA strain in prognostication and risk stratification for PAH patients was limited. Method Participants diagnosed with PAH from June 2013 to December 2022 in West China Hospital were prospectively and continuously recruited. The primary endpoint was all-cause mortality, and the second endpoint was a combination of all-cause mortality and heart failure-related repeat hospitalization. Cox regression analysis and Kaplan Meier survival analysis were performed to identify the association between variables and outcomes. C-index, 1-year mortality, and annual event rate were performed to confirm the value of RA strain in PAH patients’ risk stratification. Result A total of 283 participants (mean age, 38 ± 14 years, 84 male) were finally included, following a median follow-up duration of 31.5 months (interquartile range: 15.1-53.9 months). Significant decreases in RA reservoir (p<.001), conduit (p<.001), booster pump function (p<.001), right ventricular global longitudinal strain (RVGLS, p<.001), and free-wall longitudinal strain (RV-FWLS, p<.001) were observed in participants with all-cause mortality than those who survived. Using 16.1% and 23.6% as thresholds for RA reservoir strain, PAH patients could be divided into low-, intermediate, and high-risk groups well, with calculated 1-year mortality of 1.8%, 6.9%, and 21.4%. Moreover, RA reservoir strain presented with better 1-year mortality predictive performance than RV-FWLS (C-index, 0.82 [0.72-0.92] vs 0.72 [0.62-0.82], p<.001). The addition of RA reservoir strain had significantly increased the power of both REVEAL Lite2 and Comparative, Prospective Registry of Newly initiated Therapies for Pulmonary Hypertension (COMPERA) models (both p<.001). Conclusion RA reservoir strain was an independent predictor of all-cause mortality in individuals with pulmonary arterial hypertension and could be used to stratify participants into different risk stratification stratum.

Prevalence of stage B heart failure in healthy adults and people with type 2 diabetes

Abstract Introduction People with Type 2 Diabetes (T2D) are at increased risk of heart failure, and as such are classified as having Stage A Heart Failure (SAHF). Those with additional evidence of raised filling pressures, biochemical or structural cardiac changes, without heart failure symptoms, are deemed to have Stage B heart failure (SBHF). Identifying patients with SBHF may help determine those at highest risk of disease progression. Purpose The aim of this work was to assess the prevalence of SBHF in a cohort of asymptomatic healthy volunteers and people with T2D characterised according to current American Heart Association/American College Cardiology/Heart Failure Society of America. Methods A single-centre, prospectively recruited cohort of middle-aged asymptomatic adults with T2D and healthy volunteers, with no history or signs of cardiovascular disease, underwent comprehensive cardiac phenotyping with transthoracic echocardiography and circulating brain natriuretic peptide. Healthy volunteers with risk factors for heart failure, including hypertension and obesity, were excluded from analysis. Prevalence of SBHF was determined by comparing cardiovascular data to proposed standards, left ventricular ejection fraction and global longitudinal strain parameters were omitted from analysis due to data availability. Results We included 383 T2Ds (diabetes duration 9(5,15) years) and 65 healthy volunteers (Table 1); 91% of those with T2D and 65% of healthy volunteers met ≥1 criteria for SBHF (Table 2). Median number of SBHF criteria met in the T2D cohort was 3 (2,4); in particular, a large proportion of the cohort met defined cut offs for relative wall thickness (70.6%), lateral e’ (62.2%), septal e’ (54.1%) and LV wall thickness (47.4%). Of the 65 healthy volunteers, median number of SBHF criteria met was 1 (0,2.5). In healthy volunteers, SBHF was most commonly defined by lateral e’ (40.0%), septal e’ (38.3%), relative wall thickness (32.2%), left atrial volume indexed (22.4%) and serum brain natriuretic peptide (23.3%). Of note, brain natriuretic peptide levels met current SBHF parameters in 18.8% of healthy volunteers and 9.9% people with T2D, which may be attributable to the exclusion of obesity in the healthy volunteer group. Conclusion Using currently proposed standards, a high proportion of middle-aged asymptomatic people with T2D, and healthy volunteers without any risk factors for heart failure, would be categorised as having SBHF. These data strongly suggest that the majority of the proposed parameters for the definition of SBHF are not specific for a UK population and if applied will incorrectly classify many asymptomatic people at high risk of developing heart failure.

Iron chelation therapy failed to improve cardiac dysfunction caused by mitochondrial injury in rats with iron overload cardiomyopathy a 7T Cardiac MR research in vivo

Abstract Purpose To assess the efficacy of iron chelation therapy in improving cardiac function in iron overload cardiomyopathy (IOC) rats by using Cardiac magnetic resonance feature-tracking (CMR-FT). Methods The IOC rat model was induced by intraperitoneal injection of iron dextran over 2 months. Subsequently, 7 rats with IOC were assigned as IOC group to receive continued intraperitoneal injections of saline for an additional 2 months, while another group of 5 rats received intraperitoneal injections of deferoxamine (DFO) for the same duration, forming the IOC+DFO group. Meanwhile, a control group consisting of 7 healthy rats received intraperitoneal injections of saline for the entire duration of 4 months. All rats underwent a 7T CMR scan to assess cardiac function, myocardial iron overload, and myocardial fibrosis via cine, T2 mapping, and late gadolinium enhancement (LGE) scanning, respectively. The cardiac function analysis included left ventricular ejection fraction (LVEF) and left ventricular global longitudinal strain (GLS) using cine images. Following CMR scans, all rats underwent open-chest blood collection to detect serum iron levels, and cardiac gross specimens were then subjected to pathological staining, including hematoxylin and eosin (HE) for cardiomyocytes injury, Prussian blue for iron deposition , and Masson staining for myocardial fibrosis. Furthermore, the ultrastructure of cardiomyocyte was examined using transmission electron microscopy (TEM). Results The T2 value, measured in the septum wall at the mid-layer of the LV, and LVEF, and GLS exhibited a significant decrease in the IOC or IOC+DFO group, compared to the control group, while there were no significant difference observed between the IOC and IOC+DFO group (Fig. 1A, B, C). Myocardial fibrosis was not detected in the LGE images in both IOC and IOC+DFO group. Compared to the control group (37.5±12.5μmol/L) , serum iron levels were significantly elevated in the IOC group (368.6±181.0μmol/L) and in chelation treatment group (106.1±32.2μmol/L). Histological examination with HE staining revealed a normal arrangement of myocardial cells in all rats, without cellular degeneration or necrosis. Prussian blue staining highlighted the presence of iron particles within the myocardial interstitium in the IOC and IOC+DFO groups. Masson staining demonstrated intact myocardial muscle bundles without any evidence of myocardial fibrosis. Transmission electron microscopy (TEM) revealed myocardial mitochondria injury, characterized by ruptured outer membranes, reduced cristae, and vacuolization. Conclusions Following iron chelation therapy, the excessive iron burden in the bloodstream was alleviated. However, myocardial iron overload persisted in IOC rats, with no significant improvement in cardiac function observed. This persistence may be attributed to mitochondrial injury. The findings underscore the importance of monitoring cardiac dysfunction in patients with iron overload.CMR parameters analysis in IOC rats

The effect of the combined treatment with dulaglutide and dapagliflozin in arterial elasticity, cardiac function, albuminuria and endothelial thickness in type 2 diabetes mellitus after 12 months

Abstract Background The association between diabetes mellitus and diabetic nephropathy with vascular and endothelial properties is well established. Purpose In this study, we compared the effect of combined treatment with dulaglutide and dapagliflozin versus DPP-4 inhibitors on endothelial glycocalyx, arterial stiffness, myocardial function and albuminuria in patients with type 2 diabetes mellitus and albuminuria. Methods A total of 60 patients with type 2 diabetes mellitus and albuminuria were randomized to combined dulaglutide and dapagliflozin treatment (n=30) or DPP-4 inhibitors (DPP-4is, n=30). We measured at baseline and 4 and 12 months posttreatment: (a) perfused boundary region of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness), (b) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (c) global left ventricular longitudinal strain (GLS) (d) urine albumin-to creatinine ratio (UACR). Results Twelve months post-treatment, the combination of dulaglutide and dapagliflozin showed a greater improvement in all indices compared to DPP-4is, despite a similar reduction in glycosylated hemoglobin. Specifically, dual therapy showed greater improvements vs DPP-4is in PBR (2,10±0,31 to 1,93±0,23 μm vs 2,11±0,31 to 2,08±0,28 μm, p<0,001), in UACR (326±61 to 142±47 mg/g vs 345±48 to 306±60 mg/g, p<0,01), and in PWV (11,77±2,37 to 10,7±2,29 m/s vs 10,64±2,44 to 10,54±2,84 m/s, p<0,001), while only dual therapy showed improvement in cSBP (130,21±17,23 to 123,36±18,42 mmHg). Regarding GLS, both treatments were effective, but dual therapy showed a significantly higher percentage improvement compared to DPP-4is (18,19% vs 6,01%, respectively). Conclusions Twelve-month treatment with dulaglutide and dapagliflozin showed a greater improvement in vascular markers an albuminuria than DPP-4is in patients with type 2 diabetes mellitus and albuminuria. Early initiation of combined therapy as add-on to metformin should be considered in these patients.

Right ventricular myocardial work predicts heart failure hospitalizations irrespective of ejection fraction

Abstract Hospitalization for heart failure worsening (HFW) associates with increased subsequent rehospitalization rate and mortality irrespective of left ventricular ejection fraction (EF). However there’s little evidence regarding predictors of HFW to timely apply preventive measurements. Since right ventricular (RV) dysfunction often associates with more advanced stages of HF we assumed that RV myocardial work (MW) assessment might be used in prediction of HFW. Methods 158 patients with HF (48% female) 58±7 years on guideline directed medical therapy in sinus rhythm and with at least one hospitalization in the last 6 months were enrolled in the study. Patients with HFrEF, HFmrEF and HFpEF were evenly represented. All patients were appropriately decongested prior to the study. The primary outcome was rehospitalization, HFW or cardiovascular death. RVMW was derived from RV global strain, including interventricular septum, and noninvasively estimated pulmonary arterial pressure (PAP). Systolic PAP (sPAP) was measured as the sum of maximum RV and right atrial (RA) pressure gradient (PGmax) from tricuspid regurgitation (TR) jet peak velocity and mean right atrial pressure (RAP) estimated from diameter and collapsing of inferior vena cava. Mean PAP (mPAP) was measured as the sum of PGmean RV-RA by tracing TR jet and RAP. Diastolic PAP was estimated as dPAP = 1.5 × [mPAP − (sPAP/3)]. Then RV global work index (RVGWI), constructive (RVGCW), and efficient work (RVGWE) were derived by the software dedicated for left ventricular MW. Left ventricular global longitudinal strain, left atrial (LA) reservoir strain (LAS), LA pump strain, LA volume index (LAVi), B lines, inferior vena cava, NT-pro-BNP, TAPSE/sPAP and RVMW were also measured. Patients followed up for 12 months. Results 53 events were registered at 12 months of which 42 rehospitalizations due to HFW and 11 CV deaths. Among all parameters in the multivariate analysis lower RVGCW was associated with HFW (HR 0.978, 95% CI 0.973–0.998, p = 0.014). RVGCW was the most powerful predictor of CV events (AUC 0.91) with cut off value of 148 mmHg% that had 96% sensitivity and 88% specificity. Number of patients who died with RVGCW < 148 mmHg% was 8 of 11 (73%) total deaths (HR 0.421, 95% CI 0.083–0.986, p = 0.028). Conclusion RVGCW was a predictor of HFW and 1 year mortality in patients with HF irrespective of EF.