Measures Of Systolic Function Research Articles

Assessment of Biventricular Systolic and Diastolic Function Using Conventional and Strain Echocardiography in Children with Sickle Cell Disease Surviving 1-year After Hematopoietic Stem Cell Transplant.

Hematopoietic stem cell transplant (HSCT) is a potentially curative therapy for children with sickle cell disease (SCD). The effects of HSCT on ventricular function are not well characterized in children with SCD. Echocardiograms from children with SCD who underwent HSCT between 2007 and 2017 were retrospectively analyzed before and 1-year after HSCT. Left ventricular (LV) volumes, mass, and ejection fraction were calculated by the 5/6 area*length method. LV end-diastolic and systolic dimensions, septal, and posterior wall thickness, and fractional shortening were measured by M-mode. Mitral and tricuspid inflow Dopplers (E and A waves) as well as mitral, tricuspid, and septal tissue Dopplers (E', A') were assessed. E/A, E'/A' and E/E' ratios were calculated. Biventricular strain imaging was performed using speckle-tracking echocardiography. Peak global systolic longitudinal and circumferential LV strain, and global longitudinal right ventricular strain, as well as early and late diastolic strain rate, were measured on LV apical 4-chamber, LV short-axis mid-papillary, and RV apical views, respectively. Forty-seven children (9.7 ± 5.5years, 60% male) met inclusion criteria. Pre-HSCT, subjects had mild LV dilation with normal LV systolic function by conventional measure of ejection fraction and fractional shortening. There was a significant reduction in LV volume, mass, and ejection fraction after HSCT, but measurements remained within normal range. LV longitudinal and circumferential strain were normal pre-HSCT and showed no significant change post-HSCT. RV strain decreased after HSCT, but the absolute change was small, and mean values were normal both pre- and post-HSCT. Conventional measures of diastolic function were all normal pre-HSCT. Post-HSCT there was a reduction in select parameters, but all parameters remained within normal range. Early and late diastolic strain rate parameters showed no significant change from pre- to post-HSCT. At one-year after HSCT in children with SCD conventional measures of systolic and diastolic function are within normal limits. Except for a small decrease in RV systolic strain with values remaining within normal limits, systolic strain and diastolic strain rate values did not significantly change 1-year after HSCT.

Exercise training improves cardiovascular fitness in dilated cardiomyopathy caused by truncating titin variants

BackgroundParticipation in regular exercise activities is recommended for patients with chronic heart failure. However, less is known about the effect of exercise in patients with genetic dilated cardiomyopathy (DCM). We...

Expression of Circulating miR-21 and -29 and their Association with Myocardial Fibrosis in Hypertrophic Cardiomyopathy.

Hypertrophic Cardiomyopathy (HCM) is characterized by myocardial hypertrophy, fibrosis, and sarcomeric disarray. To evaluate the expression levels of circulating miR-21 and -29 in patients with HCM and their association with clinical characteristics and myocardial fibrosis. In this case-control study, 27 subjects with HCM, 13 subjects with hypertensive cardiomyopathy, and 10 control subjects were enrolled. Evaluation of patients' functional capacity was made by the six-minute walk test. Echocardiographic measurements of left ventricle systolic and diastolic function were conducted. Cardiac magnetic resonance late gadolinium enhancement (LGE) -through a semiquantitative evaluation- was used in the assessment of myocardial fibrosis extent in HCM patients. The expression of miR-21 and -29 in peripheral blood samples of all patients was measured via the method of quantitative reverse transcription polymerase chain reaction. Circulating levels of miR-21 were higher in both hypertensive and HCM (p<0.001) compared to controls, while expression of miR-29 did not differ between the three studied groups. In patients with HCM and LGE-detected myocardial fibrosis in more than 4 out of 17 myocardial segments, delta CT miR-21 values were lower than in patients with myocardial LGE in 3 or fewer myocardial segments (2.71 ± 1.06 deltaCT vs. 3.50 ± 0.55 deltaCT, p<0.04), indicating the higher expression of circulating miR-21 in patients with more extensive myocardial fibrosis. MiR-21 was overexpressed in patients with HCM and hypertensive cardiomyopathy. Importantly, in patients with HCM, more extensive myocardial fibrosis was associated with higher levels of miR-21.

Pilot study: Measurement of first phase ejection fraction in a sample of Egyptian people

Abstract Background Left ventricular dysfunction (LVD) constitutes the final common pathway for a number of cardiac disorders. Ischemic heart disease (IHD) is the dominant cause of heart failure (HF). The remaining etiologies include cardiomyopathy, hypertension (HTN), valvular heart diseases (VHD) and myocarditis. Data from the Framingham heart study shows that it develops in approximately 16% of men and 18% of women who had diabetes; 12% of men and 8% of women who had HTN; and 30% of both sexes who had myocardial infarction (MI). Aim of the Work to measure the first phase ejection fraction (EF1) in a sample of Egyptian population and to determine its normal value and to assess its reliability in assessment of systolic function. Patients and Methods This study is a prospective and observational clinical that was conducted at El- Mokattam health insurance &amp; Ain Shams University hospitals from October 2019 to March 2022. Results we found that mean EF1 was 35.41 ± 4.16 %, its minimal value was 26.9% and its maximal value was 43.4%. We found that EF1 was reliable and reproducible as there was no statistically significant intra observer nor inter observer variabilities (p-value was 0.547 &amp; 0.602 respectively). We found that there was no significant statistical correlation between EF1 and gender or heart rate or other demographic or clinical data. Conclusion EF1 is a simple and reproducible measurement of LV systolic function that is easily measured by transthoracic echocardiography and is considered comparable to other indices that measure LV systolic function.

Distinct Profiles and New Pharmacological Targets for Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a multifactorial condition with a variety of pathophysiological causes and morphological manifestations. The inclusion criteria and patient classification have become overly simplistic due to the customary differentiation regarding the ejection fraction (EF) cutoff. EF is considered a measure of systolic function; nevertheless, it only represents a portion of the true contractile state and has been shown to have certain limits due to methodological and hemodynamic irregularities. As a result, broader randomized clinical trials have yet to incorporate the most recent criteria for HFpEF diagnosis, leading to a lack of data consistency and confusion in interpreting the results. The primary variations between the bigger clinical trials published in this context concerning patient selection and echocardiographic characteristics were analyzed. For all these reasons, we aim to clarify the main features and clinical impact of HFpEF in a study combining imaging, bio-humoral analysis, and clinical history to identify the specific subgroups that respond better to tailored treatment. Disparate clinical characteristics and a lack of uniform diagnostic standards may cause suboptimal therapeutic feedback. To optimize treatment, we suggest shifting the paradigm from the straightforward EF measurement to a more comprehensive model that considers additional information, such as structural traits, related disorders, and biological and environmental data. Therefore, by evaluating certain echocardiographic and clinical factors, a stepwise diagnostic procedure may be useful in identifying patients at high risk, subjects with early HFpEF, and those with evident HFpEF. The present assessment underscores the significance of the precision medicine approach in guaranteeing optimal patient outcomes by providing the best care according to each distinct profile.

Longitudinal strain correlates with 6-minute walk distance whereas ejection fraction and diastolic parameters do not

BackgroundImpaired functional capacity is a common symptom in patients with heart failure. Standard measures of left ventricular (LV) function, such as ejection fraction (EF) and LV diastolic parameters, do not correlate with measures of functional capacity. The aim of this study is to determine if measures of global and regional LV strain better correlate with 6-minute walk distance than does EF or measures of LV diastolic function.Methods120 patients referred to a cardiology clinic for evaluation of known or suspected heart failure were approached for enrollment. Of those 120 patients, 58 had an echocardiogram within 3 months of enrollment with images adequate for regional and global strain assessment, had no contra-indication to exercise testing, and had no previously documented non-cardiac explanation for dyspnea on exertion. In those 58 patients, 6-minute walk distance was measured, LV EF was determined with Simpson’s biplane method, and global and regional longitudinal strain were measured with TomTec Image Arena 4.5.1 software.ResultsLV EF had no correlation with 6-minute walk distance (r = 0.22, p = 0.09) even when controlling for age, gender, and BMI (p = 0.07). No measures of LV diastolic function (including E velocity, Deceleration Time, e’ annular velocities, or E/e’) had a correlation with 6-minute walk distance. Multiple measures of global and regional LV longitudinal systolic function had a correlation with 6-minute walk distance. Longitudinal strain of the basal LV segments had the strongest correlation with 6-minute walk distance (r= -0.36, p = 0.005), and correlation persisted after controlling for age, gender, BMI, and systolic blood pressure (p = 0.004).ConclusionsLongitudinal strain correlates with a measure of functional capacity, but LVEF and traditional measures of LV diastolic dysfunction do not. Measures of longitudinal strain, especially in basal LV segments, will likely be an important marker of clinically relevant LV function.Graphical

Elevated pulmonary capillary wedge pressure, higher blood pressure, and lower cardiac index in infants with bronchopulmonary dysplasia

BackgroundLeft ventricular diastolic dysfunction indicated by elevated pulmonary capillary wedge pressure (ePCWP) may worsen cardiorespiratory status in bronchopulmonary dysplasia (BPD), but the scope of ePCWP by cardiac catheterization is not well described. MethodsThis single-center retrospective cohort study included infants with BPD without congenital heart disease, significant intracardiac shunts, or pulmonary vein stenosis who underwent cardiac catheterization from 2010 to 2021. ePCWP was defined as >10 mmHg. Quantitative measures of ventricular systolic and diastolic function were performed on existing echocardiograms. Patients with and without ePCWP were compared using the Chi-squared or Wilcoxon rank-sum tests. Associations between catheterization hemodynamics and echocardiographic parameters were assessed by simple linear regression. ResultsSeventy-one infants (93% Grade 2 or 3 BPD) met inclusion criteria, and 30 (42%) had ePCWP. Patients with ePCWP were older at catheterization (6.7 vs. 4.5 months, p < 0.001), more commonly underwent tracheostomy (66.7% vs. 29.3%, p = 0.003), and had higher mean systemic blood pressure [64.5 (56.0, 75.0) vs. 47.0 (43.0, 55.0) mm Hg, p < 0.001], higher systemic vascular resistance [11.9 (10.4, 15.6) vs. 8.7 (6.7, 11.2) WU*m2, p < 0.001), and lower cardiac index [3.9 (3.8, 4.9) vs. 4.7 (4.0, 6.3) L/min/m2, p = 0.03] at catheterization. Mean pulmonary artery pressure, pulmonary vascular resistance, and mortality were similar between the groups. Echocardiographic indices of left ventricular diastolic dysfunction did not correlate with PCWP. ConclusionsePCWP was common in infants with severe BPD who underwent cardiac catheterization in this cohort. The association between ePCWP and higher systemic blood pressure supports further study of afterload reduction in this population.

Comparing Left Ventricular Structure and Functions in End-Stage Renal Disease Using Conventional Echocardiography and 2D Speckle Tracking Echocardiography.

Patients on hemodialysis (HD) are prone to various cardiovascular complications. Two-dimensional speckle tracking echocardiography (2D STE) is an innovative technique for early myocardial dysfunction detection, even with normal ejection fraction (EF). We aim to detect left ventricle (LV) dysfunction in regular hemodialysis patients using 2D STE compared to traditional echocardiography. The study comprised 30 patients with end-stage renal disease (ESRD), subdivided according to left ventricular mass index (LVMI) into group 1 with left ventricular hypertrophy (LVH) (n=19) and group 2 without LVH (n=11). Another 30 healthy control subjects were recruited as group 3. The EF, average systolic velocity (Sa), and 2D LV strain were taken as measures of LV systolic function. The indicators for diastolic function included the E/A ratio and E velocity/peak early diastolic velocity. Regarding the parameters of LV systolic and diastolic functions assessed by traditional echocardiography, we found no significant difference between groups 1 and 2. However, using 2D STE, we observed significant differences in the average Sa velocity (p=0.025), average LV strain (p=0.03), 2D global longitudinal strain (GLS) (p=0.03), E/Ea (p=0.003), and LV myocardial performance index (MPI) (p=0.006). Also, a significant positive correlation was found between LVMI and left ventricular end-diastolic diameter (LVEDD) (p<0.01, r=0.63), EF measured by 2D (p=0.034, r=0.39), mitral E/A ratio (p=0.03, r=0.49), and mitral E/Ea (p<0.01, r=0.72). There was a significantly strong negative correlation between LVMI and 2D average LV strain (p=0.034, r=-0.39). We concluded that 2D STE is more sensitive than a conventional echo in detecting early LV systolic and diastolic dysfunction even in patients with normal EF.

Global longitudinal strain as a predictor of mortality in patients with cardiogenic shock

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Aarhus University Dagmar Marshalls Fond. Background The assessment of left ventricular (LV) function through transthoracic echocardiography (TTE) is essential for guiding diagnosis and treatment in cases of cardiogenic shock (CS). Myocardial global longitudinal strain (GLS) provides an objective and reproducible measure of systolic function, independently predicting outcomes in acute heart failure, regardless of left ventricular ejection fraction (LVEF). However, whether assessment of GLS can predict mortality in patients with CS remains unknown. Purpose In this study, we aimed to evaluate the prognostic significance of GLS in patients with CS. Methods Data from cardiac intensive care unit (CICU) patients admitted between 2007 and 2018 with CS who received vasoactive agents and/or mechanical circulatory support were analysed. GLS (as absolute values) and biplane LVEF were measured via TTE performed within 24 hours of CICU admission. Patients with CS were categorised based on the GLS quartile: mild (GLS &amp;gt;9.7%), moderate (7.0% &amp;lt; GLS &amp;lt;9.6%), severe (5.0% &amp;lt; GLS &amp;lt; 6.9%), and very severe (GLS ≤ 4.9%). CICU and in-hospital mortality were compared across GLS categories, and the relationship between GLS and mortality was assessed using multivariable logistic regression. Results The study included 626 patients with a median age of 68.6 years, a median LVEF of 31% (IQR 24 to 40%), and a median GLS of 7.0% (IQR 5.0 to 9.7%). In-hospital mortality was 29.1%. As GLS deteriorated, there was an increasing need for vasopressors (P&amp;lt;0.001). Patients with progressively lower GLS exhibited significantly higher CICU and in-hospital mortality across the GLS quartiles (Figure A; P&amp;lt;0.001). Patients in the severe (adjusted OR 2.67; p&amp;lt;0.001) and very severe category (adjusted OR 3.54; P&amp;lt;0.001) had significantly increased risk of in-hospital death compared with mild category. In multivariable analysis, every 1% decrease in GLS corresponded to a 14% higher risk of in-hospital mortality (P&amp;lt;0.001). Finally, GLS outperformed LVEF for discrimination of in-hospital mortality (P=0.002), and when both measurements were included in the same multivariable model, only GLS remained significant. When patients were divided according to whether they had GLS and/or LVEF below the median value, patients with low GLS had higher mortality irrespective of the LVEF (Figure B). Conclusion In patients with CS, GLS assessment surpasses LVEF in its prognostic value and improves risk stratification. Routine evaluation of GLS should be considered for patients with CS.Figure AFigure B

Transgender Women Exhibit a Distinct Stress Echocardiography Profile Compared With Age-Matched Cisgender Counterparts: The Mayo Clinic Women’s Heart Clinic Experience

Stress echocardiographic (SE) testing is an important modality in cardiovascular risk stratification and obstructive coronary artery disease assessment. Binary sex-based parameters are classically used for the interpretation of these studies, even among transgender women (TGW). Coronary artery disease is a leading cause of morbidity and mortality in this population. Yet, it remains unclear whether TGW exhibit a distinct stress testing profile from their cisgender counterparts. Using a matched case-control study design, the authors compared the echocardiographic stress testing profiles of TGW (n=43) with those of matched cisgender men (CGM; n=84) and cisgender women (CGW; n=86) at a single center. Relevant data, including demographics, comorbidities, and cardiac testing data, were manually extracted from the patients' charts. The prevalence of hypertension and dyslipidemia was similar between TGW and CGW and lower than that of CGM (P=.003 and P=.009, respectively). The majority of comorbidities and laboratory values were similar. On average, TGW had higher heart rates than CGM (P=.002) and had lower blood pressures than CGM and CGW (P<.05). TGW's double product and metabolic equivalents were similar to those among CGW and lower than those of CGM (P=.016 and P=.018, respectively). On echocardiography, left ventricular end-diastolic and end-systolic diameters among TGW were similar to those of CGW but lower than those of CGM (P=.023 and P=.018, respectively). Measures of systolic and diastolic function, except for exercise mitral valve E/e' ratio, which was lower in TGW than CGW (P=.029), were largely similar among the three groups. There was no difference in the wall motion score index, and therefore, no difference in the percentage of positive SE test results. This study shows, for the first time, that TGW have a SE profile that is distinct from that of their cisgender counterparts. Larger, multicenter, prospective studies are warranted to further characterize the SE profile of TGW.

Setmelanotide Administration Improves Cardiac Systolic Function in Sirtuin-3 Deficient Mice

We previously showed that activation of the brain leptin-melanocortin system, particularly melanocortin-4 receptors (MC4R), markedly improves cardiac function in experimental models of heart failure (HF) via mechanisms that are still poorly understood. Sirtuin 3 (Sirt3) is an important regulator of mitochondrial oxidative phosphorylation and deficiency of Sirt3 has been implicated in cardiovascular diseases. We recently found increased Sirt3 expression as well as increased levels of NAD+, the main Sirt3 activator, in cardiomyocytes of rats treated with chronic intracerebroventricular infusion of leptin at a dose that does not spill over into the systemic circulation. Therefore, we hypothesized that stimulation of Sirt3 activity is required for the improvement of cardiac function during activation of the brain leptin-MC4R axis. To test this hypothesis, we first examined if chronic MC4R activation, using an MC4R agonist, setmelanotide, improves cardiac function in naïve Sirt3-deficient (Sirt3-KO) mice. Baseline cardiac function was assessed by echocardiography (VisualSonics-VEVO3100®) in male and female Sirt3-KO and wild-type (WT) control mice (n=5/group) at 20 weeks of age, and then weekly during setmelanotide treatment (2 mg/kg/day — i.p. via osmotic minipump model 1002) for 3 weeks. Chronic MC4R activation with setmelanotide transiently reduced food intake in both groups and promoted weight loss in Sirt3-KO mice. Setmelanotide treatment improved systolic function in WT mice as evidenced by increases in ejection fraction and fractional shortening (EF: 52.8±4.4 vs. 72.4±4.4%; FS: 26.9±2.7 vs. 42.8±6.4%, for baseline vs. week 3, respectively) and other measures of systolic function including circumferential and longitudinal strains. Despite showing a tendency for reduced systolic function compared to WT controls at baseline, Sirt3-KO mice also exhibited improvement in systolic function with setmelanotide administration (EF: 44.1±1.8 vs. 65.3±2.9% and FS: 21.4±1.0 vs. 35.1±2.1%). No major changes were observed in measures of diastolic function. These results suggest that in a non-HF model, MC4R activation does not require stimulation of Sirt3 to improve indices of systolic function. (1R01HL163076, 1R01DK121411, P20GM104357, P30GM149404, U54GM115428, and AHA-835218). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Left ventricular diastolic function and cardiotoxic chemotherapy

BackgroundLeft ventricular ejection fraction falls when the myocardium has already lost a significant portion of its functional capacity. There are conflicting data on whether diastolic dysfunction precedes systolic dysfunction after cardiotoxic chemotherapy. We aimed to study systolic and diastolic dysfunction after cardiotoxic chemotherapy and whether diastolic dysfunction can predict subsequent risk of systolic dysfunction. It was an observational prospective cohort study, and patients receiving cardiotoxic chemotherapy were included. Baseline, demographic, and clinical details were recorded. Echocardiographic measurements of left ventricular systolic function, global longitudinal strain, and diastolic function were noted at baseline, three months, and 6 months.ResultsWe included eighty patients. The mean age of the patients was 54.92 ± 7.6 years, predominantly females (80%). The mean left ventricular ejection fraction fell from 64.92 ± 1.96 to 60.97 ± 4.94 at 6 months. Low ejection fraction was seen in 8 (10%) patients at 6 months. The mean global longitudinal strain (GLS) at baseline was − 18.81 ± 0.797 and fell to − 17.65 ± 2.057 at 6 months, with 12 (15%) patients having low GLS (< − 18). Grade 1 diastolic dysfunction was seen in 22 (27.5%) patients, and grade 2 diastolic dysfunction was seen in 3 (3.8%) patients at 6 months. There was a significant decrease in E/A ratio (inflow early diastolic velocity/Inflow late diastolic velocity), mitral tissue Doppler velocity, and an increase in isovolumic relaxation time, mitral valve deceleration time, and E/e′ (inflow early diastolic velocity/tissue Doppler mitral annular velocity), at three months and 6 months. Ejection fraction at 6 months was significantly and negatively correlated with diastolic dysfunction at three months (r = − 0.595, p = 0.02).ConclusionsCardiotoxic chemotherapy is associated with early diastolic dysfunction. Early diastolic dysfunction predicts subsequent left ventricular systolic dysfunction.

Echocardiographic parameters of cardiac structure and function in the diagnosis of acute myocarditis in adult patients: A systematic review and meta-analysis.

Transthoracic echocardiography (TTE) plays a key role in the initial work-up of myocarditis where the identification of pathologic structural and functional changes may assist in its diagnosis and management. The aim of this systematic review was to appraise the evidence for the utility of echocardiographic parameters of cardiac structure and function in the diagnosis of myocarditis in adult populations. A systematic literature search of medical databases was performed using PRISMA principles to identify all relevant studies assessing TTE parameters in adult patients with myocarditis (1995-2020; English only; PROSPERO registration CRD42021243598). Data for a range of structural and functional TTE parameters were individually extracted and those with low heterogeneity were then meta-analyzed using a random-effects model for effect size, and assessed through standardized mean difference (SMD). Available data from six studies (with a pooled total of 269 myocarditis patients and 240 controls) revealed that myocarditis can be reliably differentiated from healthy controls using echocardiographic measures of left ventricular (LV) size and systolic function, in particular LV end-diastolic diameter, LV ejection fraction (LVEF) and LV global longitudinal strain (LV-GLS) (p ≤ .01 for all). LV-GLS demonstrated the highest overall effect size, followed by LVEF and LVEDD (SMD: |0.46-1.98|). Two studies also demonstrated that impairment in LV-GLS was associated with adverse cardiovascular outcomes in this population, irrespective of LVEF. LV-GLS demonstrated the greatest overall effect size and therefore ability to differentiate myocarditis populations from healthy controls. GLS was also shown to be a predictor of adverse cardiovascular outcomes, in this population. What is already known on this subject? Myocarditis is a disease process that is often a diagnosis of exclusion, as it frequently mimics other acute cardiac pathologies. Transthoracic echocardiography is traditionally the initial imaging modality used for noninvasive structural assessment in populations with myocarditis. What might this study add? This study demonstrates that left ventricular (LV) global longitudinal strain, LV ejection fraction and LV end-diastolic diameter can differentiate between myocarditis patients and healthy controls. LV-GLS demonstrated the greatest overall effect size when comparing these two populations, in comparison to the other measures. How might this impact on clinical practice? This study demonstrates that assessment of myocardial deformation indices allows for sensitive discrimination between myocarditis patients from healthy controls. Routine assessment of LV-GLS may serve as an important diagnostic tool in the acute care setting.

Plasma Ferritin Levels, Incident Heart Failure, and Cardiac Structure and Function: The ARIC Study

BackgroundWhether iron deficiency contributes to incident heart failure (HF) and cardiac dysfunction has important implications given the prevalence of iron deficiency and the availability of several therapeutics for iron repletion. ObjectivesThe aim of this study was to estimate the associations of plasma ferritin level with incident HF overall, HF phenotypes, and cardiac structure and function measures in older adults. MethodsParticipants in the ongoing, longitudinal ARIC (Atherosclerosis Risk In Communities) study who were free of prevalent HF and anemia were studied. The associations of plasma ferritin levels with incident HF overall and heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) were estimated using Cox proportional hazards regression models. Linear regression models estimated the cross-sectional associations of plasma ferritin with echocardiographic measures of cardiac structure and function. ResultsThe cohort included 3,472 individuals with a mean age of 75 ± 5 years (56% women, 14% Black individuals). In fully adjusted models, lower ferritin was associated with higher risk for incident HF overall (HR: 1.20 [95% CI: 1.08-1.34] per 50% lower ferritin level) and higher risk for incident HFpEF (HR: 1.28 [95% CI: 1.09-1.50]). Associations with incident HFrEF were not statistically significant. Lower ferritin levels were associated with higher E/e′ ratio and higher pulmonary artery systolic pressure after adjustment for demographics and HF risk factors but not with measures of left ventricular structure or systolic function. ConclusionsAmong older adults without prevalent HF or anemia, lower plasma ferritin level is associated with a higher risk for incident HF, HFpEF, and higher measures of left ventricular filling pressure.

Effects of empagliflozin on right ventricular adaptation to pressure overload.

Right ventricular (RV) failure is the prime cause of death in patients with pulmonary arterial hypertension. Novel treatment strategies that protect the RV are needed. Empagliflozin, a sodium-glucose co-transporter-2 inhibitor, shows cardioprotective effects on the left ventricle in clinical and preclinical studies, but its direct effects on RV remain elusive. We investigated the effects of empagliflozin on RV dysfunction induced by pulmonary trunk banding (PTB). Male Wistar rats (116 ± 10 g) were randomized to PTB or sham surgery. One week after surgery, PTB animals received empagliflozin mixed into the chow (300 mg empagliflozin/kg chow; PTB-empa, n = 10) or standard chow (PTB-control, n = 10). Sham rats (Sham, n = 6) received standard chow. After five weeks, RV function was evaluated by echocardiography, cardiac MRI, and invasive pressure-volume measurements. PTB caused RV failure evident by decreased cardiac output compared with sham. PTB-empa rats had a 49% increase in water intake compared with PTB-control yet no differences in hematocrit or blood glucose. Treatment with empagliflozin decreased RV end-systolic pressures without any changes in RV cardiac output or ventricular-arterial coupling (Ees/Ea). The decrease in RV end-systolic pressure was complemented by a slight reduction in RV cross sectional area as a sign of reduced hypertrophy. Load-independent measures of RV systolic and diastolic function were not affected in PTB-empa rats compared with PTB-control. Empagliflozin treatment reduced RV end-systolic pressure in RV failure induced by pressure overload. Further studies are needed to elucidate whether this simply relates to a diuretic effect and/or additional independent beneficial RV effects.

First-phase ejection fraction to predict adverse outcomes in patients with heart failure

BackgroundFirst-phase ejection fraction (EF1) is a novel measurement of early left ventricular systolic dysfunction. We investigate its prognostic value in patients with heart failure (HF). Methods and resultsPatients with HF were prospectively enrolled from July 2019 to September 2021. A total of 228 patients were included in the final analysis. The primary endpoint was the composite of all-cause mortality or rehospitalization for HF, which occurred in 74 patients (32.46%). EF1 as well as other parameters for left ventricular function were measured in echocardiography. Time-dependent ROC showed the cutoff value of EF1 was 18.55%. Kaplan–Meier analysis indicated a higher rate of adverse events in the lower EF1 group (EF1 ≤ 18.55%) (Log-rank test P < 0.001). Cox regression analyses showed EF1 was an independent predictor with adverse events as a continuous variable (Cox model 1: per 1% change in EF1: HR = 0.92, 95%CI: 0.87–0.97, P < 0.001), as well as a categorical variable (Cox model 2: EF1 > 18.55%: HR = 0.21, 95%CI: 0.08–0.53, P < 0.001) after adjustment for hypertension, coronary artery disease (CAD), Log10 (NT-proBNP), eGFR, E/e’ and loop diuretics. Restricted cubic splines revealed a linear association between EF1 levels and the incidence of adverse events (P for non-linearity = 0.145). The subgroup analyses showed the predictive ability of elevated EF1 on the decreased risk of adverse events did not change substantially stratified by HF classification, age, CAD and hypertension. ConclusionEF1, as a novel measurement of early systolic function, is a promising predictor of adverse events among HF patients. EF1 might be considered a new measurement for risk stratification of HF.

Decline in Left Ventricular Early Systolic Function with Worsening Kidney Function in Children with Chronic Kidney Disease: Insights from the 4C and HOT-KID Studies

Adults with childhood-onset chronic kidney disease (CKD) have an increased risk of cardiovascular disease. First-phase ejection fraction (EF1), a novel measure of early systolic function, may be a more sensitive marker of left ventricular dysfunction than other markers in children with CKD. To examine whether EF1 is reduced in children with CKD. Children from the 4C and HOT-KID studies were stratified according to estimated glomerular filtration rate (eGFR). The EF1 was calculated from the fraction of left ventricular (LV) volume ejected up to the time of peak aortic flow velocity. The EF1 was measured in children ages 10.9±3.7 (mean±SD) years, 312 with CKD and 63 healthy controls. The EF1 was lower, while overall ejection fraction was similar, in those with CKD compared with controls and decreased across stages of CKD (29.3%±3.7%, 23.5%±4.5%, 19.8%±4.0%, 18.5%±5.1%, and 16.7%±6.6% in controls, CKD 1, 2, 3, and≥4, respectively, P<.001). The relationship of EF1 to eGFR persisted after adjustment for relevant confounders (P<.001). The effect size for association of measures of LV structure or function with eGFR (SD change per unit change in eGFR) was greater for EF1 (β=0.365, P<.001) than for other measures: LV mass index (β=-0.311), relative wall thickness (β=-0.223), E/e' (β=-0.147), and e' (β=0.141) after adjustment for confounders in children with CKD. Children with CKD exhibit a marked and progressive decline in EF1 with falling eGFR. This suggests that EF1 is a more sensitive marker of LV dysfunction when compared to other structural or functional measures and that early LV systolic function is a key feature in the pathophysiology of cardiac dysfunction in CKD.

Normal Values of Echocardiographic Right Ventricular Size and Systolic Function Measurements in a Healthy Japanese Population - Subanalysis of the WASE Study.

Background: Although accurate assessment of right ventricular (RV) morphology and function is clinically important, data regarding reference values for echocardiographic measurements of the right ventricle in the Japanese population are limited. Methods and Results: The World Alliance Society of Echocardiography (WASE) Normal Values Study was conducted to examine normal echocardiographic values in 15 countries. Using the WASE study database, we analyzed 2-dimensional echocardiographic parameters of RV size and systolic function in 192 healthy Japanese individuals and compared them with those obtained from 153 healthy American individuals. In the Japanese population, the absolute values of RV dimensions were smaller for women than men, although the difference disappeared after the data were adjusted for body surface area. RV dimensions, RV length and RV area were smaller in the elderly, but age did not affect RV systolic function. The absolute value, but not the adjusted value, of RV size tended to be smaller in Japanese than American individuals for both sexes. For men, RV systolic function parameters were lower in the Japanese population. This trend was not seen in women. Conclusions: The present study identified normal reference values for RV size and systolic function in a healthy Japanese population. Sex, age, and race had a significant impact on RV size; however, this trend was weak for RV systolic function.

Evaluation of disease progression in patients with ATTR amyloidosis with cardiomyopathy following treatment with patisiran: post-hoc analysis of the APOLLO-B study

Abstract Introduction Transthyretin-mediated (ATTR) amyloidosis is a progressive, fatal disease in which cardiac deposition of transthyretin (TTR) amyloid commonly manifests as cardiomyopathy. Patisiran, an RNA interference therapeutic that reduces TTR synthesis, is approved for the treatment of hereditary ATTR amyloidosis with polyneuropathy. The Phase 3 APOLLO-B study (NCT03997383) evaluated the clinical efficacy and safety of patisiran in patients with ATTR amyloidosis with cardiomyopathy (CM). Purpose This post-hoc analysis evaluated disease progression in APOLLO-B patients following treatment with patisiran vs placebo, based on the European Society of Cardiology (ESC) expert consensus on monitoring patients with ATTR amyloidosis with CM every 6–12 months using three domains: Clinical/Functional, Laboratory Biomarker, and Imaging/Electrocardiography (ECG). Methods Patients with ATTR amyloidosis with CM were randomised (1:1) to intravenous patisiran 0.3 mg/kg or placebo every 3 weeks for 12 months. Disease progression was defined at Month 12 (M12) relative to baseline using Clinical/Functional criteria (≥1 heart failure-related hospitalisation, increased New York Heart Association class ≥1, decline in Kansas City Cardiomyopathy Questionnaire ≥5, or decline in 6-minute walk test ≥30 metres), Laboratory Biomarker criteria (increased N-terminal prohormone B-type natriuretic peptide ≥30% and absolute change ≥300 ng/L, troponin I ≥30%, or ATTR disease stage ≥1), and Imaging/ECG criteria (conduction disturbances or change in left ventricular wall thickness ≥2 mm, change in diastolic dysfunction grade ≥1, or change in systolic function measurements). One marker from each domain provides the minimum criteria for disease progression. Results At M12, the patisiran group (N = 180) had improved odds of no disease progression compared with the placebo group (N = 178; odds ratio [OR] 1.4; 95% confidence interval [CI] 0.77, 2.55) (Figure). The patisiran group had benefits in Clinical and Functional markers vs placebo at M12 (OR 1.58; 95% CI 1.03, 2.42). Patisiran also showed favourable changes in Laboratory Biomarkers vs placebo at M12 (OR 2.14; 95% CI 1.33, 3.43) and a favourable trend in Imaging assessments/ECG vs placebo at M12 (OR 1.31; 95% CI 0.80, 2.15). Conclusion In this post-hoc analysis of APOLLO-B, fewer patisiran-treated patients had disease progression with respect to clinical, functional, and biomarker parameters vs placebo. The risk of disease progression was lower by Clinical/Functional and Laboratory Biomarker composite criteria, and trended lower by individual criterion from the ESC consensus statement among patisiran-treated patients at 12 months vs placebo patients. Long-term follow-up will further assess the impact of patisiran in patients with ATTR amyloidosis with CM.Figure 1

The effects of empagliflozin on right ventricular adaptation to pressure overload

Abstract Background Right ventricular (RV) failure is the prime cause of death in patients with pulmonary arterial hypertension. Novel treatment strategies that protect the RV are needed. Empagliflozin, a member of the new anti-diabetic sodium-glucose co-transporter-2 inhibitors, shows a cardioprotective effect on the left ventricle in clinical and preclinical studies, but its direct cardiac effects on the RV remain elusive. Purpose To investigate the effects of empagliflozin on RV dysfunction induced by pulmonary trunk banding (PTB). Methods Male Wistar rat weanlings (116±10 g) were randomized to PTB or sham surgery. One week after surgery, PTB animals were randomized to empagliflozin 20 mg/kg/day mixed in the chow (300 mg empagliflozin/kg chow) (PTB-empa, n=10) or standard chow (PTB-control, n=10). Sham rats (Sham, n=6) received standard chow. After five weeks, RV function was evaluated by clinically relevant methods including echocardiography, cardiac MRI, and invasive pressure-volume measurements. Results PTB increased RV end-systolic pressures four-fold and caused RV hypertrophy with a 55 % increase in RV/(left ventricle + septum) weight ratio in PTB-control rats compared with sham. RV failure was evident by a decrease in cardiac output (PTB-control: 1.07±0.06 mL/s vs sham: 2.06±0.24 mL/s, p=0.0136). PTB-empa rats had a slight but non-significant weight reduction and a 33 % increase in water intake compared with PTB-control, yet no differences in hematocrit or blood glucose were observed. Treatment with empagliflozin decreased RV end-systolic pressures by 11 % (PTB-empa: 81±3 mmHg vs PTB-control: 91±2 mmHg, p=0.0091) without any effects on RV cardiac output. This decrease in RV end-systolic pressure in PTB-empa rats was complemented by less decreased minimum dp/dt and less increased maximum dp/dt compared with PTB-control without changes in the ventriculo-arterial coupling (Ees/Ea) (PTB-empa: 0.58±0.08 vs PTB-control: 0.67±0.14, p=0.8170). Load-independent measures of RV systolic and diastolic function were not affected in PTB-empa rats compared with PTB-control. Conclusion PTB caused RV failure in all rats subjected to the procedure. Empagliflozin treatment showed promising effects in pressure overload induced RV failure by reducing end-systolic pressure. Our study supports that treatment with empagliflozin has no toxic or adverse effects on the failing RV. Further studies are needed to explore empagliflozin’s potential beneficial role against RV failure.