Reduction In Left Ventricular Ejection Fraction Research Articles

Outcome of transcatheter mitral valve repair in heart failure patients with reduced ejection fraction and severe left ventricular dilatation

Abstract Introduction The COAPT trial demonstrated the benefit of transcatheter edge­to­edge mitral valve repair (TEER) for heart failure patients who had reduced ejection fraction (HFrEF) with symptomatic secondary mitral regurgitation (MR). However, patients with severe left ventricular (LV) dilatation were not included in the COAPT trial. Furthermore, disproportionate LV dilatation was suggested as a possible explanation for the lack of benefit in the MITRA­FR trial. Purpose The purpose of this study was to assess the safety and efficacy of TEER in HFrEF patients with severe LV dilatation. Methods We studied 75 HFrEF patients who underwent mitral valve repair between 2018-2021. Reduced LV ejection fraction (LVEF) was defined as LVEF of 40% or less. These patients were categorized with and without severe LV dilatation based on left ventricular end-diastolic volume index (LVEDVI) using a median cut­off value of >139ml/m2 in men and >128cm/m2 in women. Results There were 37 patients with severe LV dilatation (D) and 38 without (ND). Median LVEDVI was 172 [149-190] ml/m2 in the D group vs 120 [105-127] ml/m2 in the ND group. Compared to the ND patients, patients with severe LV dilatation were more treated with SGLT2-inhibitor (rate 24% vs 3%), had lower LVEF (30 [25-31] % vs 32 [30-36] %), and higher BNP (1160 [683-2586] vs 619 [396-1253] pg/ml). There was no significant difference in MR grade (4 [3-4] vs 4 [3-4]), EROA (0.32 [0.22-0.66] vs 0.34 [0.24-0.48] cm2), NYHA class (3 [2-4] vs 3 [2-3]) and mean systolic pulmonary pressure (31 [20-43] vs 34 [25-41] mmHg). Peri­procedural adverse events were rare in both groups. 1 patient had pseudoaneurysm in the ND group, and 1 patient had cardiogenic shock and 1 patient had stroke after the procedure in the D group. At discharge, there was marked improvement in MR grade (1 [1-2] vs 1 [1-2] for both). D group had a tendency of higher reduction in LVEDVI (-12 [-24--1] vs -5[-13-4] ml/m2) than ND group. BNP level of the D group had a significantly higher degree of decline before discharge (-458 [-141--1566] to -102 [+51--306] pg/ml) than that of ND group. No differences were noted in mortality between two groups (Figure). Conclusion TEER in HFrEF patients with severe LV dilatation seems to provide similar outcomes compared to patients with less severe dilatation. Further studies are needed to clarify the indication and establish the effectiveness of TEER in these patients.

Sex differences in aortic stenosis progression and myocardial response

Abstract Background Aortic stenosis (AS) produces an increased afterload and consequently left ventricular (LV) remodeling. While current guidelines recommend the same echo-doppler criteria for diagnosis and grading of AS for men and women, different sex-specific patterns of cardiac remodeling, and eventually damage, have been reported. Whether these different patterns are caused by sex-related AS progression rate or myocardial response is less well known. Aim We aim to compare longitudinal changes in aortic valve and cardiac function between women and men with AS to investigate sex-related differences in AS progression and cardiac remodeling. Methods Patients with mild-to-severe AS and LV ejection fraction (LVEF) ≥ 50 % at least in 2 transthoracic echocardiograms (TTE) were retrospectively identified. Prosthetic and bicuspid valves were excluded. Serial TTEs provided a multiparametric framework to compare AS severity, progression rate and induced cardiac changes between sexes. Results 914 patients were included (median follow-up time of 6.8 years) and 52 % (473) were female. Both sexes had similar baseline aortic peak velocities (APV) (2.9±0.9 m/s), mean pressure gradient (MPG) (27±13 mmHg) and LVEF (60±5 %). Women were older (75±9 vs 73±8 years; p<0.001), had smaller body surface area (BSA) (1.70±0.15 vs 1.88±0.16 m2, p<0.001), proportionally lower stroke volume (SV) (82±19 mL vs 91±22 mL, p<0.001), lower indexed LV mass (iLVM) (118±33 g/m2 vs 125±28 g/m2, p<0.001) and higher indexed left atrial (LA) volume (39±13 vs 49±20 mL/m2, p<0.001). The average annual progression rate of APV and MPG was similar for both groups (2 mmHg/year and 0.14 m s-1 year-1). After multivariate adjustment including time-dependent aortic valve replacement, women had a higher incidence of severe LV hypertrophy as measured by iLVM (HR=1.16, CI=1.08-1.91, p<0.01), moderate-to-severe tricuspid valve regurgitation (HR=2.03, CI=1.01-4.07, p<0.05) and pulmonary hypertension (PHT) (HR=1.49, CI=1.02-2.18, p=0.04) at 5 years. Similar incidence rates were seen for LV dilation, LVEF reduction and mitral valve regurgitation. All-cause mortality rates were similar between groups (p=0.30). Conclusion This study suggests that under similar static and dynamic loading conditions, women will develop severe LV hypertrophy and PHT earlier than men, possibly reflecting sex-specific response differences intrinsic to the myocardium. This suggests that the definition of AS severity may benefit from a shift from a valve-focused to a myocardial-integrative approach taking gender into account.

Anthracycline therapy induces an early decline of cardiac contractility with transient edema in low risk patients with breast cancer

Abstract Background Cancer therapy-related cardiac dysfunction (CTRCD) is a dreaded complication of anthracycline therapy in the treatment of breast cancer. CTRCD most frequently appears in patients with cardiovascular risk factors or known cardiovascular disease. There is limited evidence of incidence and prospective course of anthracycline-induced CTRCD in young patients without common risk factors for CTRCD. Purpose To longitudinally investigate a cohort of young women on anthracycline treatment due to breast cancer without cardiovascular risk factors or known cardiovascular disease. Methods 59 women with first-diagnosed breast cancer and planned anthracycline regime-based therapy were enrolled. Exclusion criteria were cardiovascular risk factors or known cardiovascular disease. We conducted a longitudinal assessment before, immediately after- and 12 months after cancer therapy with general laboratory, electrocardiograms, echocardiography and cardiovascular magnetic resonance (CMR), including myocardial relaxometry with T1, T2 and extracellular volume mapping. Results Every single patient experienced a drop in CMR-measured left ventricular ejection fraction (LVEF) of 6 ± 3 % immediately after cancer therapy. According to the novel definition 32 patients (54.2%) developed CTRCD after 12 months defined by reduction in LVEF, global longitudinal strain (GLS) and/or biomarkers elevation (Figure 1). LVEF reduction was accompanied by a decrease in stroke volume and cardiac power index while enddiastolic volume index remained stable. Global myocardial T2 relaxation times as well as myocardial mass increased coincidently with a decline in wall-thickening. While T2 values and myocardial mass normalized after 12 months, LVEF and GLS remained impaired. Conclusion Among breast cancer patients without pre-existing risk factors for CTRCD anthracyclines induce a decline of myocardial contractility in every single patient, which may lead to an increased risk of future cardiovascular diseases in these patients. Figure 1: Patients with diagnosed CTRCD directly after CT and after 12 months follow up stratified by underlying CTRCD criteria. Boldness of arrows proportionally represents the number of patients changing between the criteria. Some patients fulfilled more than one criterium for CTRCD.Graphical Abstract Figure 1

Differences in the prevalence of cardiovascular toxicity in a cohort of female breast cancer patients according to the different cardiotoxicity definitions

Abstract Background The definition of cancer therapy-related cardiac dysfunction (CTRCD) has evolved in the past ten years, as Cardio Oncology has consolidated as a new medical discipline. However, great heterogeneity is noted among the published criteria of the different types of cardiotoxicities by the different scientific societies. In order to mitigate this variability, a new definition of CTRCD has been recently proposed by the International Cardio-Oncology Society (IC-OS) and endorsed by the latest 2022 ESC Guidelines on cardio-oncology. CTRCD is now classified into different degrees of severity according to symptoms, left ventricular ejection fraction (LVEF) reduction guided by echocardiography and elevation of cardiac biomarkers. Purpose we aimed to assess the impact of the new consensus definition of CTRCD in the reclassification of cardiotoxicity in a breast cancer cohort of female patients receiving potentially cardiotoxic therapies (CT) attended in our third-level hospital. Methods we retrospectively analyzed and compared the incidence of the different subtypes of CTRCD in a cohort of female breast cancer patients evaluated in our hospital from 2018 to 2021 according to both the previous 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity and the latest 2021 ICOS definition. Results a cohort of 193 women with a breast cancer diagnosis and receiving CT was analyzed. Mean age was 58 ± 11 years and 57 % of the patients (110) had a least one cardiovascular risk factor, with no past history of cardiac disease. According to the previous ESC 2016 criteria, 16 patients (8.3%) had cardiac dysfunction associated with cancer treatment whereas with the 2021 IC-OS new definition, a total of 23 women (12%) would have been satisfied the CTRCD criteria. Of Those, 11 were asymptomatic and 7 had severe CTRCD. Overall, this would have translated into a 30% rise in the incidence of patients experiencing any type of cardiotoxicty (p < 0.0001). Conclusion(s) by using the new IC-OS criteria for CTRCD, a significant increase in the prevalence of cardiotoxicity was noted in our population, which may translate the higher sensitivity of the proposed criteria to detect clinical or subclinical cardiovascular damage derived from cancer treatment.

First month global longtudinal strain for predicting early pacemaker-induced left ventricular dysfunction (PIVD) six month after pacemaker implantation

Abstract Background Pacemaker-induced ventricular dysfunction (PIVD) and pacemaker-induced cardiomyopathy (PICM) emerged as a complication following right ventricular permanent pacemaker (PPM) implantation, showing a great occurrence in the first year. Finding an early predictor of PIVD and PICM is crucial in order to alleviate mortality, morbidity, and increase health-care cost efficiency. Purposes to find new predictor by analyzing effect of first month GLS using 2D-speckle tracking echocardiography and reduction of left ventricular ejection fraction (LVEF), known as PIVD, in the first 6 month after PPM implantation. Methods A single center, prospective cohort study was conducted to all patients with normal LVEF, indicated for PPM implantation. Data of GLS was measured before and after one month of PPM implantation. Data of LVEF was measured before and six month after PPM implantation. The change of GLS in one month after PPM implantation was measured as delta GLS, and the change of LVEF in six month was measured as delta EF. Results Fifty-three patients from May 2018 until October 2020 was enrolled for this study based on inclusion and exclusion criteria. Patient’s baseline characteristics show 62±14 years of age, most of them had hypertension (54.7%) and had single chamber pacemaker implantation (81.1%). Study analysis reveals that ejection fraction (EF) reduce significantly after six months pacemaker implantation (66,5±5,6% become 60,7±10.7%; p= <0,00001). There were 6 patients (11.3 % ) suffering PICM. Correlation analysis between the change of GLS in the first month and the change of LVEF in the first six months after PPM implantation was statistically significant with moderate correlation (p<0.00001; r= -0.486). Linear regression analysis shows that every 1 point decrease of first month GLS, affecting 1.83 point decrease of sixth month LVEF (b= -0.1837, p=<0.00001). Conclusion There is significant moderate correlation between the change of GLS in the first month and early reduction of LVEF in the first 6 months after PPM implantation.The Scheme of Research Sampling Method

Abstract 15115: Efficacy and Safety of miR-132 Inhibitor CDR132L in Patients With Reduced Left Ventricular Ejection Fraction After Myocardial Infarction: Rationale for and Design of the HF-REVERT Trial

Background: Inhibition of miR-132 effectively prevents and reverses heart failure (HF) in relevant models, making it an attractive HF target. CDR132L is a synthetic antisense oligonucleotide (ASO) selectively blocking miR-132. Translational in vitro and in vivo studies have demonstrated meaningful efficacy of CDR132L on left ventricular (LV) structure and function. CDR132L was safe and well tolerated in a Phase 1b study in chronic HF patients. The indicative effects of the miR-132 inhibitor CDR132L may be particularly beneficial in patients with active adverse remodelling, e.g. after acute myocardial infarction with early decline in ejection fraction. These patients have been relatively understudied and therapeutic options are limited. Method: The HF-REVERT (P h ase 2, Multicenter, Randomized, Parallel, 3-arm, Placebo-controlled Study to Assess E f ficacy and Safety of CD R 132L in Pati e nts with Reduced Left V entricular E jection F r ac t ion (≤ 45%) after Myocardial Infarction; NCT05350969) is a proof-of-concept study to evaluate the efficacy of CDR132L in improving cardiac function and safety in patients with reduced LV ejection fraction (LVEF). HF-REVERT aims to assess the efficacy and safety of 5 mg/kg and 10 mg/kg CDR132L, given as 3 single intravenous doses administered 28 days apart as an add-on to standard-of-care treatment, in a larger cohort of patients (N = 280) with HF and reduced LVEF (≤ 45%) after MI with a follow-up of 10 months. Key inclusion criteria are the diagnosis of acute STEMI/NSTEMI and the development of systolic dysfunction (LVEF ≤ 45%) after MI index event and elevated N-terminal pro B-type natriuretic peptide (NT-proBNP). The study consists of a 6-month double-blind treatment period with a read out of the primary endpoint LVESVI (left ventricular end systolic volume index) followed by a 6-month open label observation period. Discussion: The HF-REVERT trial currently tests CDR132L in patients with MI and systolic dysfunction. This trial may therefore underpin the concept of miR-132 inhibition to prevent/reverse cardiac remodeling in HF patients. The results will inform the design of a subsequent outcome trial to test the effect of CDR132L in HF patients.

Abstract 19028: Revascularization in Ischemic Cardiomyopathy With Left Ventricular Systolic Dysfunction- Percutaneous Intervention (PCI) vs Medical Therapy

Background: The benefits of percutaneous revascularization in patients with reduced Left Ventricular (LV) systolic function secondary to stable coronary artery disease (CAD) is still ambiguous. We aim to compare the survival benefits of PCI in patients with Ischemic cardiomyopathy with reduced LV Ejection Fraction (LVEF <35%) compared to Medical Therapy (MT) alone. Methods: A systematic search was conducted in PubMed, Google Scholar, and Cochrane databases from inception to 5 th June 2023. Among 108 results from the systematic search, a total of 4 studies (2080 patients) were included. Our outcome of interest was all-cause mortality in patients undergoing PCI vs. medical therapy. We used random-effects models to aggregate data and to calculate pooled incidence and relative risk (RR) with 95% confidence intervals (CIs). Results: Of 1082 patients undergoing revascularization with PCI and 998 patients in the medical therapy arm, the outcome of all-cause mortality occurred in 168 patients (15.5%) in the PCI group and in 200 patients (20.0%) in the medical therapy group (Hazard ratio, 0.88; 95% confidence interval [CI], 0.71 to 1.09; P=0.25). However, a non-statistical trend toward lower mortality was noted in the PCI arm. Low heterogenicity was noted between the studies. Conclusions: In patients with ischemic cardiomyopathy with reduced LV systolic function (EF <35%), revascularization with PCI is associated with similar all-cause mortality compared to medical therapy.

Abstract 14417: Regional 4D Cardiac Magnetic Resonance Strain Associates With Late Gadolinium Enhancement in Duchenne Muscular Dystrophy Associated Cardiomyopathy

Introduction: Cardiomyopathy (CM) is the leading cause of death in Duchenne muscular dystrophy (DMD). Onset and clinical progression are varied. Cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) can detect fibrofatty replacement prior to decreased left ventricular ejection fraction (LVEF) but requires administration of gadolinium contrast agents. Non-contrast methods to characterize CM onset and progression could decrease scan time and exposure to gadolinium. Using a novel 4D (3D+time) regional strain analysis method, we hypothesized that the regional magnitude of surface area strain (E a ) would be significantly decreased in DMD patients with LGE and that E a would correlate with decreased LVEF . Methods: Short-axis cine CMR images for 43 pediatric DMD patients (13.6 ± 4.2 years) were compiled into 4D sequences for regional strain analysis (Fig. 1A). For all 4D sequences, epi- and endocardial borders were segmented across one cardiac cycle for kinematic analysis using a custom-built MATLAB graphical user interface (MathWorks, Natick, MA). Regional E a was measured by determining the relative change in the localized 4D endocardial surface mesh compared to end-diastole. Unpaired t-test and Spearman’s rho were used to determine statistical significance and correlation. Results: DMD patients had a range of CM severity: 13 with reduced LVEF of <55% (30% of total) and 28 with LGE (65% of total). Peak E a was significantly different between patients with and without LGE in the basal inferior ( p =0.022), basal inferolateral ( p <0.001), basal anterolateral ( p =0.002), mid inferolateral ( p =0.004), mid anterolateral ( p =0.018), and apical anterior ( p <0.032), regions (Fig.1B). Basal E a also correlated significantly with LVEF ( rho =-0.45, p< 0.001; Fig. 1C). Conclusion: Regional E a from 4D CMR in DMD was reduced in patients with LGE compared to those without LGE particularly in the basolateral regions. Peak basal E a correlated with a reduction in LVEF. LVEF.

Abstract 16825: Brahma Related Gene-1 (BRG1) Protein Mediates Helpful Compensatory Response to Retard Development of Heart Failure

Background: Chromatin remodeling can modulate transcription by changing gene accessibility. Brahma Related Gene-1 (Brg1) protein, which is an adenosine triphosphate catalytic subunit that supports chromatin remodeling, has been implicated in development of hypertrophic cardiomyopathy. However, contribution of Brg1 to the development of heart failure (HF) has not been clearly elucidated. Hypothesis: We hypothesize that Brg1 mediates compensatory response to cardiac stress; therefore, loss of Brg1 function will accelerate development of HF. Methods: The myosin light chain-2 Cre/loxP system was used to produce cardiac myocyte specific deletion of Brg1(-/-) mouse model with floxed littermates as control. Results: At baseline, Brg1(-/-) hearts showed mildly reduced left ventricular ejection fraction (LVEF). Aging to 12 months caused LV dilation and further reduction of LVEF in Brg1(-/-). We used trans-aortic constriction (TAC) for pressure overload challenge and chose similarly severe TAC induced pressure gradient as indicated by similarly fast peak flow velocities across the constriction. At 2-weeks post-TAC, Brg1(-/-) hearts exhibited severely reduced LVEF, severely dilated LV, and decreased ability to thicken LV wall during systole. In contrast, control hearts did not dilate and maintained its LVEF with increased LV wall thickness. Thus, Brg1 deletion greatly diminished the heart’s ability to compensate for aging and pressure challenge, thereby accelerating development of heart failure with reduced ejection fraction (HFrEF). Separately, RNA sequence analyses of 12-months aged hearts showed Brg1 deletion caused upregulation of 810 genes including HF associated long noncoding RNA XIST and down regulation of 50 genes, while 3-months old hearts were not significantly different. Conclusion: Brg1 mediates compensatory responses that are helpful to the heart to prevent development of HF; therefore, it is a potential treatment mechanism for HF.

Abstract 14093: Effects of Continuous Accelerated Pacing on Cardiac Structure and Function in Patients With Heart Failure With Preserved Ejection Fraction: Insights From the MyPACE Randomized Clinical Trial

Introduction: Heart failure with a preserved ejection fraction of 50% or higher (HFpEF) is prevalent and has few evidence-based therapies. In a trial of HFpEF patients with specialized pacemakers, treatment with an accelerated personalized pacing rate averaging 75 bpm (myPACE) markedly improved quality of life, NT-proBNP, physical activity, and atrial fibrillation burden compared with the standard lower rate setting of 60bpm (usual care). Methods: Provider-initiated echocardiographic studies obtained before and after the trial were assessed for changes in left ventricular (LV) structure and function amongst participants who continued their pacing assignment. The analytic approach aimed to detect differences in standard and advanced echocardiographic parameters within and between study arms. Results: Of the 100 trial participants, 16 patients in the myPACE arm and 20 in the usual care arm had a qualifying set of echocardiograms with a mean±SD time of 3.7±2.0 years apart. Heart rates were expectedly higher among myPACE patients after the trial (in bpm: myPACE 75±6 vs. usual care 65±7, p<0.001). Sustained exposure to moderately accelerated pacing resulted in a reduced septal wall thickness (myPACE 1.07±0.05mm vs usual care 1.23±0.04, p=0.008) and a lower LV mass to systolic volume ratio (myPACE 1.52±0.09 vs. usual care 1.84±0.05, p=0.038) accompanied by a small reduction in LV ejection fraction (in %: myPACE 55±1 vs usual care 60±1, p=0.015). These changes were paralleled by marked improvements in heart failure-related quality of life (MLHFQ points: myPACE 17±21 vs usual care 28±22, p<0.001). Markers of diastolic function and LV performance were not affected. Conclusions: Exposure to continuous accelerated pacing in HFpEF is associated with a reduced LV wall thickness and a lower mass to systolic volume ratio and ejection fraction that remained within normal limits.

Abstract 11820: Importance of Resting Heart Rate Assessment in Autonomic Dysfunction Evaluation in Congestive Heart Failure Patients

Background: Novel treatments in congestive heart failure (CHF) aim at ameliorating autonomic dysfunction. Autonomic dysfunction typically manifests with resting tachycardia and blunted baroreceptor reflex response and been classically described in CHF with reduced LV ejection fraction (EF) but baroreflex function in CHF with preserved EF has not been well investigated. Methods: A single center prospective study was conducted by measuring resting and lowest heart rates (HR) during voluntary breath holding in 118 CHF patients, 68 ± 14 years old, 50 females (42.3%), BMI 30.1 ± 8.5 kg/m 2 , HTN in 97 (82.2%), CAD in 64 (54.2%), diabetes in 49 (41.5%), and chronic lung disease in 39 patients (33.1%). HFrEF less than 40% was found in 41 (34.7%) patients; for the purposes of analysis HRmrEF and HFpEF groups were combined. Beta-blockers were used in 92 (78%) and non-dihydropyridine calcium channel blockers were used in 7 (5.9%) patients. Results: The majority of HFpEF or HFmrEF patients had resting HR less than 80 bpm (55/77 patients, 71.4%), while the majority of HFrEF patients had resting HR more than 70 bpm (32/41 patients, 78%, p=0.015). Furthermore, HFpEF and HFmrEF patients had lower breath holding HR (69.7 ± 14.7 bpm in HFpEF and HFmrEF patients vs. 77.6 ± 13.9 bpm in HFrEF patients, p=0.005). There was a trend of increased resting HR in patients with Class IV CHF (p=0.179). Furthermore, class IV CHF patients manifested with increased breath holding HR (68.9 ± 15.3 bpm in combined NYHA class I-II, 69.9 ± 12.2 bpm in NYHA class III, 79.9 ± 16.1 bpm in NYHA class IV, p=0.02). Regardless of the CHF class (p=0.060) and/or LV EF (p=0.913), increased resting HR was associated with higher breath holding HR. Patients with baseline HR <60 bpm had breath holding HR of 54.6 ± 6.2 bpm, as compared to 94.9 ± 9.0 bpm in patients with baseline HR >90 bpm, p<0.001. Conclusion: In CHF patients, increased resting HR is a strong indicator of abnormal baroreceptor function. HRmrEF and HFpEF patients have lower resting and breath holding HR, suggesting less pronounced autonomic dysfunction, as compared to more pronounced autonomic dysfunction in HFrEF patients. Additional studies are needed to investigate whether autonomic modulation treatment is equally beneficial in patients across the LVEF spectrum.

Abstract 17497: Natural History of the Left Ventricular Ejection Fraction in Heart Failure and Sudden Cardiac Death

Background: A clinical diagnosis of heart failure (HF) is associated with increased risk of sudden cardiac death (SCD), but only HF with severely reduced LV ejection fraction (HFrEF, EF ≤35%) is utilized for risk stratification. Guideline-directed medical therapy and heart disease processes may improve or reduce the LVEF. Hypothesis: There is significant variation of LVEF over time among HF patients with SCD. Methods: From a large, prospective population-based study of SCD in the Northwest US (catchment population 1 million, 2002-2018), we identified all consecutive patients with a diagnosis of HF and prior assessment of LVEF. The sub-group of patients with at least 2 prior LVEF evaluations (earliest and latest in relation to SCD) was determined. Results: A total of 1622 individuals suffered SCD with a known diagnosis of HF (65% male, age 72±14) of which 434 had 2 LVEF evaluations at least 1 yr apart prior to their SCD. At earliest evaluation, 100 (23%) had HFrEF (73% male, age 67±13), 88 (20%) had HF with moderately reduced EF (HFmrEF, 35<ef<50) (71% male, age 72±12), and 246 (57%) had hf with preserved ef (hfpef, ef≥50) (57% 72±12). comparing the earliest latest assessment of lvef, mean lvef in hfref increased by 9±14 percentage points (p<0.001) from 27±6 to 36±14; hfmref decreased over time -4±14 (p="0.003)" 43±4 39±14; hfpef -8±13, 62±7 54±14. each subtype changed substantially (mean 2.9±1.5 yrs), sizeable proportions re-classified into different subtypes (Figure). Overall, the HF LVEF subtype was unchanged in 58% and altered in 42% (p<0.001). Conclusions: Based on the LVEF, at least 40% of HF sub-types were re-classified prior to SCD and risk assessment would be variable depending on when LVEF was measured. These findings highlight the limitations of using the LVEF as the only risk predictor of SCD.

Novel echocardiographic markers for left ventricular filling pressure prediction in heart failure with preserved ejection fraction (ECHO-PREDICT): a prospective cross-sectional study.

Heart failure with preserved ejection fraction is a complex clinical syndrome associated with a high level of morbidity and mortality, constituting 56% of heart failure cases and showing an increasing prevalence. The E/Ea ratio, used for echocardiographic assessment of left ventricular (LV) filling pressure, has been commonly recommended as a noninvasive measure. However, its validity lacks robust prospective validation in patients with preserved LV ejection fraction, and its accuracy has been questioned in comparison to patients with reduced LV ejection fraction. The objective of this study was to evaluate the accuracy of novel echocardiographic markers incorporating peak E velocity, left atrial volume index (LAVi), and pulmonary artery systolic pressure (PAP) for noninvasive estimation of LV end-diastolic pressure (LVEDP) against invasive measurement. In this cross-sectional study conducted at a tertiary care hospital, a sample size of 122 participants was utilized. Statistical analyses including independent samples t-test, χ2 test, and linear regression analysis were employed to explore correlations and predict outcomes. The results indicated that Group 1 (LVEDP <20mmHg) had a mean age of 59.25 years, while Group 2 (LVEDP >20mmHg) had a mean age of 56.93 years. Mitral E velocity positively predicted LVEDP, while Mitral E/A ratio showed a negative association. Notably, (E+PAP)/2, (E+LAVi)/2, and Mitral E exhibited good discriminative ability, with respective area under the curve values of 0.840, 0.900, and 0.854. (E+LAVi)/2 demonstrated the highest discriminatory power, with a threshold of 40.100, yielding high sensitivity (0.971) but relatively low specificity (0.302) in predicting LVEDP greater than 20. These findings emphasize the accuracy and utility of combining diastolic variables and peak E velocity as markers for left ventricular filling pressure in patients with a high burden of cardiac disease. Additionally, the study highlights the importance of these parameters in assessing cardiac abnormalities and supports the potential of novel echocardiographic parameters, particularly (E+LAVi)/2, in predicting LVEDP greater than 20. Further research is warranted to validate and explore the prognostic implications of these parameters in larger patient populations, ultimately improving the diagnosis and management of cardiac disease and enhancing clinical outcomes.

Superiority of left heart deformation in early anthracycline-related cardiac dysfunction detection

ObjectiveThis study aimed to assess the incidence of early cancer therapy-related cardiac dysfunction (CTRCD) and the characteristics of left and right heart deformations during anthracycline chemotherapy.MethodsWe prospectively enrolled a cohort...

The relationship between insulin resistance, serum alkaline phosphatase, and left ventricular dysfunction following myocardial infarction

The occurrence of heart failure following acute myocardial infarction (AMI) significantly increases the risk of post-infarction mortality. Alkaline phosphatase (AP) is considered to be an independent predictor of cardiovascular disease (CVD) and adverse outcomes. Furthermore, in recent years, alkaline phosphatase has been associated with insulin resistance (IR). Our aim was to investigate the correlation between IR substitutes (triglyceride-glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio), AP, and LV dysfunction in patients admitted after AMI. The retrospective study included 810 patients who underwent coronary angiography for myocardial infarction at the First Hospital of Hebei Medical University from August 2018 to December 2021. Patients were categorized into three groups based on their serum AP levels. Clinical characteristics at admission, cardiac echocardiography findings, coronary angiography results, and biochemical markers such as serum AP levels and triglycerides (TG) were recorded during hospitalization. Left ventricular ejection fraction (LVEF) was assessed using cardiac echocardiography conducted from the time of admission until the coronary angiography procedure. A total of 774 patients with AMI were included in this study. The TyG index is significantly correlated with the TG/HDL-C ratio. (R = 0.739, P < 0.001). Binary logistic regression analysis revealed that elevated serum AP (OR 2.598, 95% CI 1.331–5.071, P = 0.005), presence of the left anterior descending (LAD) artery as the infarct-related artery (IRA) (OR 2.452, 95% CI 1.352–4.449, P = 0.003), and triglyceride (TG) levels (OR 0.652, 95% CI 0.429–0.992, P = 0.046) were protective risk factor for an admission LVEF < 40% following AMI. The serum alkaline phosphatase and LAD as IRA are independent risk factors for severe reduction in LVEF during hospitalization for AMI. Conversely, triglyceride are independent protective factor for severe reduction in LVEF during AMI hospitalization.

Allogeneic Hematopoietic Cell Transplantation with Non-Myeloablative Conditioning and Post-Transplant Cyclophosphamide Prophylaxis in Patients with Reduced Systolic Function

Post-transplantation cyclophosphamide (PTCy) has become standard of care for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic cell transplantation (alloHCT), allowing for expanded donor options. However, there is scant literature examining outcomes of patients with reduced systolic function receiving PTCy. The present study aimed to describe our experience in performing alloHCT in patients with reduced systolic function, including their nonrelapse mortality (NRM), overall survival (OS), and cumulative incidence of early cardiac events (ECEs). We performed a retrospective descriptive analysis using the Johns Hopkins Hematologic Malignancy database. From 2017 through 2021, 1118 consecutive patients underwent alloHCT with nonmyeloablative (NMA) conditioning and PTCy. Forty-three of those patients had a pretransplantation left ventricular ejection fraction (LVEF) ≤45% measured by transthoracic echocardiography. Patients whose LVEF improved on treatment prior to transplantation were also included. These 2 cohorts were stratified into 2 groups-heart failure with reduced ejection fraction (HFrEF) and heart failure with recovered ejection fraction (HFrecEF)-and subgroup analyses compared NRM, OS, and cumulative incidence of ECEs, including arrhythmia, coronary artery disease, reduction in LVEF, and pericardial effusion, within 100 days post-transplantation. The median LVEF was 40% to 45% (range, 30% to 45%) for the 31 patients undergoing transplantation with HFrEF and 35% to 40% (range, 20% to 45%) for the 12 patients with HFrecEF. The NRM for all 43 patients was 16% (95% confidence interval [CI], 5% to 27%) at 100 days and 23% (95% CI, 11% to 36%) at 2 years. The NRM was 23% (95% CI, 8% to 38%) at 100 days and 26% (95% CI, 10% to 42%) at 2 years for the HFrEF cohort and 0 at 100 days and 18% (95% CI, 0 to 41%) at 2 years for the HFrecEf cohort. The OS at 3 years was 41% (95% CI, 26% to 62%), 40% (95% CI, 25% to 65%) and 38% (95% CI, 14% to 100%) in the combined, HFrEF, and HFrecEF cohorts, respectively. The cumulative incidence of any ECE was 37.2% (95% CI, 22% to 51.9%), including 39% of HFrEF subjects and 33% of HFrecEF subjects. Grade ≥3 toxicities were seen in 56% of patients. Reduced ejection fraction was the most common ECE. One death was attributable to a cardiac etiology. Cardiac toxicities seemed to be more frequent and severe in patients with a history of systolic dysfunction, but this did not lead to worse survival outcomes. This study adds to and extends the existing literature supporting the use of NMA conditioning and PTCy in patients with systolic dysfunction.

Preoperative sST2 levels relate to myocardial remodeling and cardiac function improvement after cardiac valve surgery.

We aim to investigate the correlation between preoperative soluble suppression of tumourigenicity 2 (sST2) and postoperative myocardial remodelling and cardiac function in patients with valvular heart disease. This retrospective study included patients who underwent heart valve surgery at the General Hospital of Northern Theatre Command from July 2019 to June 2020. Preoperative, early postoperative, and 1-month postoperative cardiac ultrasound data were collected. Multivariable linear regression was used to analyse the factors associated with preoperative sST2 and postoperative cardiac function parameters. A receiver operator characteristic curve analysis was used to analyse the predictive value of sST2 for left ventricular ejection fraction (LVEF) reduction at 1month after surgery. This study included 156 patients. Left ventricular end-systolic volume (b=0.125, P=0.004), atrial fibrillation (b=7.933, P=0.003), and coronary artery disease (b=5.826, P=0.043) were correlated with the preoperative sST2 levels. Preoperative sST2 was independently associated with early postoperative left ventricular end-systolic volume (b=-0.136, P=0.035), left ventricular end-diastolic volume (b=-0.225, P=0.036), and LVEF (b=0.056, P=0.008). At 1month after surgery, LVEF (r=-0.234, P=0.023) and reduction in LVEF (r=-0.316, P=0.002) were negatively correlated with preoperative sST2. The area under the receiver operator characteristic curve of preoperative sST2 in predicting LVEF reduction at 1month was 0.646, with a sensitivity of 0.357 and a specificity of 0.918. Preoperative sST2 levels are related to early postoperative myocardial remodelling and have a predictive value for the improvement of cardiac function 1month after surgery.

Left ventricular rotational mechanics and left ventricular volumes: is there a relationship in healthy adults?-three-dimensional speckle-tracking echocardiography-derived insights from the MAGYAR-Healthy Study.

Left ventricular (LV) rotational mechanics play a crucial role in LV pump function by strengthening and improving its efficacy. Dependence of LV rotational parameters on left atrial volumes has already been demonstrated. The evaluation of the effect of LV rotational mechanics on LV volumes was purposed in a population of healthy subjects by three-dimensional speckle-tracking echocardiography (STE). The study comprised 175 healthy subjects with a mean age of 32.8±12.2 years (79 males). All subjects underwent a complete physical examination, laboratory assessments, standard 12-lead electrocardiography and two-dimensional Doppler and three-dimensional STE, the results of these examinations were within the normal range. Increased basal LV rotation was associated with increased LV volume measured in end-systole and impaired LV ejection fraction. Increased apical LV rotation was associated with reduced LV volumes assessed in end-diastole and in end-systole and increased ejection fraction of the LV. Elevated basal LV rotation showed associations with increased LV mass. In case of increasing basal LV rotation, apical LV rotation showed a decreasing tendency and LV twist showed a tendency of increasing. Similarly, lower basal LV rotation and increased LV twist were seen with increasing apical LV rotation. Increasing LV end-diastolic volume was associated with increasing LV volume measured in end-systole and preserved ejection fraction of the LV. Increasing LV end-systolic volume was associated with increasing LV end-diastolic volume and reduction of LV ejection fraction. Increasing LV volumes were associated with increasing LV mass. While increased LV volumes were associated with reduced apical LV rotation and twist, basal LV rotation did not show significant changes. LV rotational mechanics are strongly associated with LV volumes in healthy adults suggesting its volume-dependence.

Diagnostic capabilities of echocardiographic indicators of acceleration time and the ratio of acceleration time to total left ventricular ejection time in the assessment of severe aortic stenosis in patients with reduced left ventricular ejection fraction

Objectives: 1) to evaluate the diagnostic capabilities of AT and AT/ET in determining severe AS in patients with reduced LV EF and low stroke volume.2) to determine the threshold values for AT and AT/ET in the diagnosis of severe AS in patients with low stroke volume and low transaortic gradient.Materials and methods. This is prospective single center study included 70 patients with low transaortic pressure gradient, reduced LV ejection fraction was and severe aortic stenosis. All patients have been examined from 2017 to 2022. Inclusion criteria for the study are: isolated AV stenosis with, reduced LV RF, low transaortic pressure gradient. Severity of AS was identified based on dobutamine stress echocardiography and aortic valve area (AVA). Severe stenosis was defined as AVA&lt; 1 cm2.Result. A statistically significant and high negative correlation was found between the AVA and AT/ET ratio, (r = 0.77, p &lt; 0.001) and weak correlation with the AT indicator (r = 0.41, p = 0.01). The RoC-analysis showed the greatest predictive ability in the differential diagnosis of severe AS for the ratio AT/ET (AUC = 0.84 ± 0.54, p &lt; 0.001) and the lower predictive ability for the indicator AT (AUC = 0.63 ± 0.72, p &lt; 0.02). The optimal threshold value for determining severe AS for the AT / ET &gt; 0.32 (sensitivity of 92%, specificity of 70%), for AT &gt; 99 (sensitivity of 81%, specificity of 88%). Multiple logistic regression analysis revealed that the AT/ET ratio is the only echocardiographic parameter that has a significant impact on the differential diagnosis of severe AS in patients with reduced LV EF (OR 1.5; 95% CI 1.2–1.9, p = 0.001). There was low interobserver variability in measurements of AT score (intraclass correlation coefficient was 0.93 [95% CI, 0.80-0.97] and AT/ET ratio (intraclass correlation coefficient was 0.88 [95% CI, 0.75–0.95]).Conclusions.In patients with AS and reduced LV stroke volume the AT/ET ratio is highly sensitive and well reproducible in the diagnosis of severe AS. The AT index has a weak diagnostic ability of severe AS in that patients.The threshold value of AT/ET &gt;0.32 can diagnose severe AS with a high degree of probability in patients with reduced LV stroke volume and reduced transaortic gradients with reduced LV EF.

The sympathetic nervous system in heart failure revisited.

Several attempts have been made, by the scientific community, to develop a unifying hypothesis that explains the clinical syndrome of heart failure (HF). The currently widely accepted neurohormonal model has substituted the cardiorenal and the cardiocirculatory models, which focused on salt-water retention and low cardiac output/peripheral vasoconstriction, respectively. According to the neurohormonal model, HF with eccentric left ventricular (LV) hypertrophy (LVH) (systolic HF or HF with reduced LV ejection fraction [LVEF] or HFrEF) develops and progresses because endogenous neurohormonal systems, predominantly the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS), exhibit prolonged activation following the initial heart injury exerting deleterious hemodynamic and direct nonhemodynamic cardiovascular effects. However, there is evidence to suggest that SNS overactivity often preexists HF development due to its association with HF risk factors, is also present in HF with preserved LVEF (diastolic HF or HFpEF), and that it is linked to immune/inflammatory factors. Furthermore, SNS activity in HF may be augmented by coexisting noncardiac morbidities and modified by genetic factors and demographics. The purpose of this paper is to provide a contemporary overview of the complex associations between SNS overactivity and the development and progression of HF, summarize the underlying mechanisms, and discuss the clinical implications as they relate to therapeutic interventions mitigating SNS overactivity.