Changes In Left Ventricular Ejection Fraction Research Articles

Predictors of Improvement in Left Ventricular Systolic Dysfunction in Patients with Atrial Fibrillation Undergoing Catheter Ablation: Systematic Review

Background: Left ventricular systolic dysfunction (LVSD) can improve after catheter ablation (CA) in many patients with AF. However, prospective prediction of response can be challenging. The aim of this study was, therefore, to perform a systematic literature review of features associated with improvement in left ventricular ejection fraction (LVEF) in patients with AF and LVSD undergoing first CA. Method: Systematic search of Ovid MEDLINE, Embase and Cochrane Library databases up to 24 January 2024, for studies involving adult patients with LVSD receiving treatment for AF. The focus was on research articles and clinical trials reporting features associated with changes in LVEF following CA. The review followed PRISMA guidelines. Results: A total of 789 unique articles were reviewed and 20 were included in the systematic review. Sixty-nine per cent (range, 54–79%) of included patients met the criteria for responder status, which were based on LVEF improvement (usually an increase in LVEF >10% or to >50% at follow-up). Baseline surrogates of myocardial fibrosis on MRI (R2=−0.67), electroanatomical mapping (R2=−0.93) and biochemical surrogates have shown the strongest association with LVEF change. Left atrium and LV chamber size, diastolic dysfunction ECG-based parameters and a known heart failure aetiology have shown prognostic value independently and in combination. Discussion: Imaging, clinical and ECG-based surrogates of LV fibrosis may be pre-CA markers of LVEF improvement in patients with AF and LVSD. However, the confounding effect of procedural outcomes should be considered. A composite risk stratification tool would have clinical utility in risk stratification and patient selection; however, prospective studies are needed.

Straining to predict mortality in low flow low gradient aortic stenosis patients undergoing TAVR: can GLS and myocardial work parameters improve outcomes?

Abstract Background Classic low flow low gradient aortic stenosis (LFLG-AS) represents 5-10% of the Aortic Stenosis (AS) population and is associated with poorer clinical outcomes when compared to other AS subtypes. The survival rate of these patients is low (40–60% at 2-yrs) with conservative management. The TOPAS study found a transfemoral Transcatheter Aortic Valve Replacement (TAVR) adjusted hazard ratio (HR) of 0.23 and Surgical Aortic Valve Repair adjusted HR of 0.36. However, mortality within 2-yrs of TAVR can still be as high as 30%-50%. Currently there are no pre-TAVR echocardiographic markers that reliably predict post-TAVR outcomes. Global longitudinal strain (GLS), a load-dependent measurement, in conjunction with the recently emerging load-independent measurements, global myocardial work index (GWI) and global myocardial work efficiency (GWE), have the potential to improve peri-procedural risk stratification. Purpose This study sought to establish the sensitivity and specificity of using GLS, GWI, GWE, Contractile Reserve, and Left Ventricle Ejection Fraction (LVEF) in predicting mortality for LFLG AS patients undergoing TAVR. Methods We measured baseline GLS, GWI, GWE, Contractile Reserve, and LVEF, using GE Echo Pac AFI software (ver. 203) in patients with LFLG AS (n=29, age 79 ± 8 yrs, 69% males) that underwent low dose Dobutamine Stress Echocardiography (DSE) pre-TAVR (2017 to 2023). Contractile flow reserve (defined as >20% increase in LV stroke volume (SV) during DSE was recorded. LVEF was re-measured by a single operator. Receiver operating curves (ROC) were created to predict mortality using SPSS. Results Baseline LVEF was 37.6 ± 9.3% with mean AV gradient of 30 ± 10 mmHg prior to TAVR. 59% (17) had contractile reserve (25 ± 19% increase in SV). There was -0.3 ± 15.7% change in LVEF and 24% (10) patients had ≥10% improvement in LVEF at 1-yr Total mortality was 21% (6) and heart failure admission was 34% (10) at 1-yr Post TAVR, GLS (AUC 0.82, p=0.017), GWI (AUC 0.688, p=0.209) and GWE (AUC 0.82, p=0.001) can predict 1-yr mortality compared to baseline LVEF (AUC 0.536, p=0.83), and contractile reserve (AUC 0.551, p=0.132) (Figure 1). Baseline GLS of ≥ -7.5% (83% sensitivity, 83% specificity), GWI ≤ 817 mmHg% (83% sensitivity, 67% specificity) and GWE ≤74% (83% sensitivity, 67% specificity) can predict 1-yr mortality. Conclusion This study demonstrates that GLS, GWI, and GWE possess superior predictive capabilities for predicting mortality within 1-yr post-TAVR compared to baseline LVEF and contractile reserve. A baseline GLS of ≥ -7.5%, GWI ≤ 817 mmHg%, and GWE ≤ 74% were identified as thresholds with high sensitivity and specificity. This study has notable limitations, being a single-center retrospective study with a small sample size, however, the findings justify replication of this study in a larger, multicenter cohort, in an effort to improve risk stratification in the patients with LFLG-AS being considered for TAVR.

Ability of dynamic chest radiography to identify left ventricular systolic dysfunction in heart failure.

Dynamic chest radiography (DCR) can estimate haemodynamic parameters in heart failure (HF). However, no studies have evaluated its ability to determine cardiac systolic function in HF. This experimental study investigates the correlation between left ventricular (LV) ejection fraction (LVEF) and DCR image parameters in HF. Ninety-one patients with acute HF (median age, 58 years; males, 75%) (cardiologist diagnosis using the Framingham criteria) underwent DCR and transthoracic echocardiography after treatment for the uncompensated phase of HF. The LV apex pixel value (PV) change was measured by DCR. Correlations between the PV change and LVEF, as well as sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of DCR, were evaluated. LVEF and LV apex PV change were correlated in all patients (R = 0.428, P < 0.001) and in patients with LVEF < 50% (n = 38; R = 0.355, P = 0.029), < 40% (n = 31; R = 0.343, P = 0.059), and < 30% (n = 23; R = 0.321, P = 0.135). There was no significant correlation for patients with LVEF ≥ 50% (n = 53; R = - 0.004, P = 0.980). The LV apex PV change rate cutoff values for identifying LVEF < 50%, < 40%, and < 30% were 9.3% (AUC: 0.761, sensitivity: 0.698, specificity: 0.789, P < 0.001), 5.5% (AUC: 0.765, sensitivity: 0.883, specificity: 0.645, P < 0.001), and 5.5% (AUC: 0.767, sensitivity: 0.838, specificity: 0.696, P < 0.001), respectively. DCR may be useful to identify LV systolic dysfunction based on LVEF in acute HF.

Left ventricular function improvement during angiotensin receptor-neprilysin inhibitor treatment in a cohort of HFrEF/HFmrEF patients.

Heart failure (HF) patients may lack improvement of left ventricular (LV) ejection fraction (LVEF) despite optimal HF medication comprising an angiotensin receptor-neprilysin inhibitor (ARNI). Therefore, we aimed to identify key predictors for LV functional enhancement and prognostic reverse cardiac remodelling in HF patients on ARNI treatment. We retrospectively analysed 294 consecutive patients with HF with reduced (HFrEF) or mildly reduced (HFmrEF) ejection fraction in our 'EnTruth' patient registry. LVEF was determined by echocardiography at initiation of ARNI and at 12months of follow-up. We assessed the predictive value of clinically relevant patient-, HF- and treatment-related parameters in regard to changes in LVEF and all-cause mortality using medoid clustering and the XGBoost machine learning algorithm. Cluster analysis integrating clinically relevant patient characteristics unveiled four characteristic sub-phenotypes of patients with HFrEF and HFmrEF, respectively. Distinct clusters exhibit a strong (P<0.05) therapeutic response to ARNI treatment and enhanced LV function. Key patient criteria, such as duration and aetiology of HF, renal function and de novo ARNI treatment, were significantly (P<0.05) associated with change of LVEF and independently predicted cardiac remodelling. By training various machine learning models on relevant clinical parameters, stratification of LVEF improvement by XGBoost resulted in a high prediction accuracy. The stratification of patients with HFrEF [area under the receiver operating characteristic curve (AUC)=0.77] and HFmrEF (AUC=0.70) led to an increased diagnostic accuracy of LVEF improvement in the validation cohort. Using machine learning, the likelihood of cardiac remodelling following ARNI treatment, as indicated by our newly established EnTruth score, was directly associated with absolute LVEF improvement in both HFrEF (r=0.51, P<0.0001) and HFmrEF (r=0.42, P=0.001). Ultimately, patients with HFrEF and a high EnTruth score have a lower risk of all-cause mortality (P<0.05 in survival analysis). Recognition of essential clinical factors by integrating machine learning and cluster analyses may help to identify HF patients benefiting from improvement of LVEF following ARNI treatment. Early identification of those patients with a high response to ARNI treatment may allow a more refined selection of patients benefiting from an early escalation of HF treatment or interventional therapy.

Software Discrepancies in Radionuclide-Derived Left Ventricular Ejection Fraction.

Gated equilibrium radionuclide angiography (ERNA), or multigated acquisition scanning, is a well-established technique to monitor left ventricular ejection fraction (LVEF) in patients treated with potentially cardiotoxic chemotherapy. To determine the results of a true change in LVEF, low inter- and intrareader variability is important. The aim of this study was to investigate inter- and intrareader variability in LVEF measurements using 2 different commercially available software packages with cardiac MR (CMR) as a reference standard. Methods: In 46 ERNA scans, LVEF was measured by 2 experienced nuclear medicine technologists, using the 2 software packages Xeleris and Corridor4DM. All patients had CMR performed within 1.5 h from ERNA. CMR-derived LVEF was measured by a cardiologist using cvi42 software. Eight patients were reanalyzed to investigate intrareader variability. Bland-Altman analysis was used to assess agreement between readers and software. Repeated-measures ANOVA was used to assess interactions between readers and software. Differences in mean LVEF were compared using a t test. The Lin concordance correlation coefficient (CCC) was used to test LVEF agreement between software packages and readers and the reference CMR results. Results: Corridor4DM had a significantly higher mean LVEF than did Xeleris. No significant interreader difference was observed within the same software. ANOVA found that readers did not influence LVEFs. The CCC between software packages was similar for both readers, at 0.409 for reader 1 and 0.418 for reader 2. Both software packages showed a significant LVEF bias compared with CMR (4% for Xeleris vs. 11% for Corridor4DM). For both readers, the CCC for correlation with MRI was higher for Xeleris (0.438/0.572) than for Corridor4DM (0.257/0.244). Conclusion: A high degree of variability was found between the 2 different software packages for the calculation of LVEF. No significant difference in LVEF was found between readers using the same software. Corridor4DM gave higher LVEF estimates than did Xeleris. Our findings suggest that different software programs for assessing LVEF in ERNA examinations are not interchangeable. The utmost caution is recommended if switching between different types of software.

Mechanical Circulatory Support With Impella in High-Risk Patients With Chronic Total Occlusion and Complex Multivessel Disease.

The therapeutic management of patients with multivessel disease and severe left ventricular dysfunction is complex and controversial. The aim of this study was to analyze the clinical outcomes and the changes in left ventricular ejection fraction (LVEF) in patients with severe left ventricular dysfunction and at least one chronic total occlusion (CTO) undergoing percutaneous coronary intervention (PCI) with hemodynamic support provided by Impella. Retrospective, multicenter study enrolling patients with severe left ventricular dysfunction and severe coronary artery disease with at least one CTO who required percutaneous mechanical circulatory support with Impella, from January 2019 to December 2023. The primary endpoints were the incidence of MACE (composite of cardiovascular death, acute myocardial infarct, and target lesion revascularization) at 90 days. The secondary endpoint was changes in LVEF and functional class during the same period. A total of 27 patients (34 CTOs) were included in the study. The mean SYNTAX score was 35 ± 11. The median J-CTO score of 2 (1-3). At 90 day of follow-up, there were three MACE (11%), two cardiovascular deaths and one TLR; three vascular complications were related to access for the Impella device (only one required invasive treatment); and LVEF improved significantly after revascularization (delta LVEF: 10% [CI 95% 6, 15]). A total of 81% of patients improved their angina or dyspnea status at 90 days. In high-risk patients with severe left ventricular dysfunction with complex coronary disease including CTO, PCI with mechanical circulatory support using the Impella device is associated with favorable safety and efficacy outcomes at short-term follow-up.

Outcomes of Worsened Left Ventricular Ejection Fraction After Transcatheter Aortic Valve Replacement.

Left ventricular ejection fraction (LVEF) worsening after transcatheter aortic valve replacement (TAVR) was common in clinical practice. However, the effect of acute worsening LVEF is unclear. All consecutive patients who underwent TAVR between January 2016 and May 2022 were analyzed. Patients were divided into worsened LVEF and non-worsened LVEF according to whether or not they had an LVEF decline of ≥5% at discharge. Survival at follow-up was compared between two groups. Logistic regression analysis was used to determine independent predictors of worsening LVEF. A total of 439 patients were included in the analysis, and 112 (25.5%) patients had worsened LVEF. Worsened LVEF was more common in patients with LVEF ≥50%. After multivariable logistic analysis, only baseline LVEF was associated with worsening LVEF [OR=1.06 (95% CI: 1.04-1.08), P < 0.001]. The decline in LVEF recovered to the baseline after one month. There were no significant differences in survival between patients with and without worsened LVEF (Log rank P = 0.48). Acute worsening of LVEF after TAVR was not uncommon but did not affect survival. It could recover to baseline levels after one month. Routine post-TAVR echocardiography should focus on other metrics rather than acute LVEF changes.

Quantitative assessment of early changes in myocardial extracellular volume during postoperative adjuvant chemotherapy in patients with breast cancer via dual-layer spectral detector computed tomography: a cohort study.

The major of anticancer therapies induce a wide spectrum of cardiotoxic effects. Early identification of anticancer treatment-associated cardiotoxicity is critical to informing decisions on subsequent interventions. Myocardial extracellular volume (ECV) has been proposed as a useful parameter for quantifying the early cardiotoxicity of cancer-related treatment. This study used dual-layer spectral detector computed tomography (CT) technology to simultaneously assess cardiac function and myocardial ECV, characterizing the early changes in parameters during breast cancer therapy. A single-center cohort study was conducted that prospectively enrolled 40 women with breast cancer (mean age 47.5±10.8 years) who underwent postoperative adjuvant chemotherapy between January 12, 2022, and November 2, 2023, with available data from baseline to 3 months after chemotherapy of cardiac computed tomography (CCT), ultrasound cardiography (UCG), electrocardiography, and serum biomarkers. Midventricular and global ECVs of the left ventricle were measured based on an iodine map of the late enhancement phase of dual-layer spectral detector CT. Changes in cardiac function parameters, ECVs, and cardiac biomarkers from baseline to the 3-month follow-up were analyzed. Correlation coefficients between the changes in cardiac function parameters and ECVs were calculated. Between baseline and 3 months, there was no significant change in left ventricular ejection fraction (LVEF) on UCG (67.1%±3.8% vs. 66.3%±4.3%, P=0.29) or LVEF on CCT (65.4%±5.9% vs. 64.3%±7.4%, P=0.28). Heart rate increased over 3 months of follow-up (75.2±11.5 vs. 81.7±12.3 bpm; P<0.01). After normalization to body surface area (BSA), cardiac output on CCT/BSA ratio (CCT-CO indexed) (3.5±0.6 vs. 3.8±0.6 L/(min·m2); P=0.01) and left ventricular late (active) filling volume/BSA ratio (LVLFV indexed) (13.5±3.7 vs. 15.8±4.2 mL/m2; P<0.01) significantly increased, while there was a significant decrease at the 3-month follow-up in left ventricular early (passive) filling volume/BSA ratio (LVEFV indexed) (33.3±6.6 vs. 30.6±8.2 mL/m2; P=0.01) and LVEFV/LVLFV ratio (2.7±1.1 vs. 2.1±0.9; P<0.01). Midventricular and global ECVs were elevated at 3 months, significantly so for the midanterior ECV (24.0%±4.5% vs. 25.6%±3.1%; P=0.04), midaverage ECV (25.6%±2.5% vs. 27.0%±2.9%; P=0.01) and global ECV (25.4%±2.4% vs. 27.3%±2.7%; P<0.01). Although changes in ECVs were not associated with changes in LVEFs, global ECV changes were moderately correlated with changes in left ventricular end-diastolic volume/BSA ratio (CCT-LVEDV indexed) (r=0.52; P<0.001), left ventricular stroke volume/BSA ratio (CCT-LVSV indexed) (r=0.56; P<0.001), CCT-CO indexed (r=0.40; P=0.01), and LVEFV indexed (r=0.41; P=0.009). CCT-derived ECV was used to evaluate myocardial changes in the early stage of chemotherapy before LVEF significantly decreased. The increases in ECV were not correlated with LVEF. The changes in myocardial ECVs were moderately correlated with cardiac function parameters. ECV may be a useful biomarker for detecting cardiotoxicity in patients with breast cancer in the early stage of anticancer therapy.

Medical Therapy and Clinical Outcomes in Cardiac Sarcoidosis Patients With Systolic Heart Failure

Cardiac sarcoidosis (CS) may result in systolic heart failure (heart failure with reduced ejection fraction [HFrEF]), but its response to guideline-directed medical therapy (GDMT) remains uncertain. We investigated 881 patients evaluated for CS to identify those with diagnosed CS, left ventricular ejection fraction (LVEF) ≤40% at diagnosis, and follow-up echocardiogram within 11-24 months. Demographics, LVEF, GDMT as quantified by Kansas City Medical Optimization (KCMO) score, and immunosuppressive treatment were recorded. The primary outcome was a composite of event-free survival (unplanned heart failure hospitalization, left ventricular assist device [LVAD]/heart transplant, or death). Seventy-nine (9%) CS patients met the inclusion criteria (35% female, median age 57 years, mean LVEF 30.9%, median New York Heart Association class II [46%], mean number of GDMT agents 1.7, and mean KCMO score 31.8). Most (87%) were treated with immunosuppressive treatment. At follow-up (median 16 months), the mean number of GDMT agents increased to 2.2 (P=0.02), and the mean KCMO score to 70.1 (P<0.001). Mean LVEF improved to 39.9% (excluding LVAD/transplant; P<0.001) and the change in LVEF was correlated with follow-up KCMO score (P<0.001). The primary outcome occurred in 13 (16%) patients and differed by KCMO score (log-rank P<0.001), but not by immunosuppressive treatment (log-rank P=0.36). GDMT optimization is associated with better cardiac remodeling and clinical outcomes in CS patients with HFrEF.

Left ventricular systolic function after percutaneous coronary intervention: patterns of change and prognosis according to clinical presentation of coronary artery disease.

Whether there are differences in the left ventricular ejection fraction change (ΔLVEF) after percutaneous coronary intervention (PCI) and its association with long-term prognosis according to coronary artery disease (CAD) presentations is unknown. We assessed ΔLVEF after PCI and its association with 5-year mortality in various CAD presentations. This study included 8181 patients with paired (before and 6-8months after PCI) angiographic LVEF measurements: 4582 patients with chronic coronary disease (CCD), 1972 patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and 1627 patients with ST-segment elevation myocardial infarction (STEMI). ΔLVEF (LVEF at 6-8months minus baseline LVEF) was classified as follows: decline (ΔLVEF < 0), moderate improvement (ΔLVEF > 0 to < 10%) and large improvement (ΔLVEF ≥ 10%). The primary endpoint was 5year mortality. In patients with CCD, NSTE-ACS and STEMI, ΔLVEF (median [25th-75th percentiles]) was 0.0% [-3.0%; 4.0%], 1.0% [-2.0%; 5.0%] and 3.0% [-2.0%; 10.0%], respectively (P < 0.001). In patients with a decline, moderate improvement and large improvement of LVEF, 5-year mortality was 10.0%, 10.4% and 12.3% in patients with CCD, 10.8%, 10.7% and 18.1% in patients with NSTE-ACS and 10.6%, 8.2% and 5.2% in patients with STEMI. After adjustment, ΔLVEF was associated with 5-year mortality in patients with CCD (adjusted hazard ratio [HR] = 0.90, 95% confidence interval [0.83-0.97]) and STEMI (adjusted HR = 0.85 [0.75-0.95]) but not in patients with NSTE-ACS (adjusted HR = 0.97 [0.85-1.10]), with all 3 risk estimates calculated for 5% increment in the ΔLVEF. The type of CAD presentation appears to impact both LVEF change after PCI and its association with 5-year mortality.

Shock wave-pretreated ADMSCs of cell-sheet scaffold (CSS) patched on the left ventricular wall (LVW) inhibited LVW remodeling in mini-pig MI: role of CSS on counteracting Laplace's Law of LVW stress - experimental study.

We investigated whether shock wave (SW)-pretreated autologous adipocyte-derived mesenchymal stem cells (ADMSCs) seeded in the cell-sheet scaffold (CSS) could inhibit left ventricular (LV) remodeling and improve LV ejection fraction (LVEF) in old myocardial infarction (MI). Mini-pigs ( n =20) were divided into group 1 (sham-operated control), group 2 (old MI), group 3 (old MI + autologous ADMSCs/1.0×10 7 in CSS on LV myocardium), and group 4 [old MI + SW (0.12mJ/mm 2 for total 140 shots)-pretreated ADMSCs in CSS on LV myocardium]. Treatments started on day 28 after MI induction. In-vivo and in-vitro studies were conducted. Cell viability/relative mitochondria DNA expression/mitochondrial cytochrome C/adenosine triphosphate concentration in ADMCSs and protein expressions of angiogenesis factors [vascular endothelial growth factor (VEGF)/stromal cell-derived factor-1 (SDF-1)/mitochondrial respiratory chain complexes I-IV/oxygen consumption rate] were higher in group 4 than in group 3 ( P <0.001). By day 180, LVEF and small vessel numbers in the peri-infarct or infarct area were highest in group 1, lowest in group 2, and significantly lower in group 3 than in group 4. In contrast, the LV dimension was opposite to the pattern of change in LVEF in all groups ( P <0.0001). The basal/middle/apical infarct and fibrotic areas were inversely related to LVEF in all groups (all P <0.0001). Protein levels of angiogenetic markers (SDF-1α/C-X-C chemokine receptor type 4/VEGF/angiopoietin-1) were significantly and persistently increased from groups 1 to 4. In contrast, protein levels of endothelial cell markers (von Willebrand factor or endothelial nitric oxide synthase) showed an identical pattern to LVEF in all groups (all P <0.0001). SW pretreatment of ADMSCs seeded in CSS offered significant benefits in preserving LV performance and ameliorating LV remodeling in mini-pigs with old MI.

The Impact of Percutaneous Coronary Intervention on Echocardiographic Parameters in Patients with Chronic Total Occlusion of the Coronary Arteries with Diverse Left Ventricular Ejection Fractions: A Single-Center Retrospective Study

Background: Chronic total occlusion (CTO) of the coronary arteries presents a significant challenge in the management of coronary artery disease, with diverse clinical manifestations and implications for patients with varying left ventricular ejection fraction (LVEF). The aim of this study is to investigate the impact of percutaneous coronary intervention (PCI) on echocardiographic parameters in patients with CTO and different LVEF, so as to optimize the care and outcomes of patients. Methods: We selected patients with CTO of coronary arteries treated at our hospital from June 2021 to June 2023 consecutively in this study. The patients were divided into two groups based on their LVEF: the low to moderate LVEF (&lt;50%) group and the high LVEF group. Echocardiographic parameters, medication use, and demographic characteristics were assessed before and after PCI. Statistical analyses were conducted to compare changes in LVEF, left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), global longitudinal strain (GLS), and left ventricular wall motion score (LVWMS) between the two LVEF groups. Results: A total of 100 patients including 67 patients with Low &amp; Mid-range LVEF and 33 patients with High LVEF were included. Patients in the low and mid-range LVEF group demonstrated significant improvements in LVEF (p = 0.010), LVESV (p = 0.013), LVEDV (p = 0.034), GLS (p = 0.014), and LVWMS (p = 0.014) following PCI. In contrast, no significant changes in these parameters were observed in the high LVEF group after PCI. Conclusion: This study demonstrates that PCI leads to significant improvements in LVEF, LVESV, LVEDV, GLS, and LVWMS in patients with low to moderate LVEF, indicating potential benefits of revascularization in this patient subset.

Efficacy and safety of sacubitril/valsartan on postoperative atrial fibrillation in adult patients undergoing cardiac surgery: a real-world observational study.

The mechanism underlying new-onset postoperative atrial fibrillation (POAF) in adult cardiac surgery is not well understood. However, efficient pharmacological methods to prevent and treat arrhythmic complications are still lacking. In the present study, we explored the efficacy and safety of sacubitril/valsartan (sac/val) in the control of POAF in adult cardiac surgery patients. Between January 2021 and December 2021, 667 eligible adult patients who underwent cardiac surgery at the Affiliated Hospital of Qingdao University were enrolled. The participants were divided into two groups according to whether sac/val was used: the sac/val group (N = 101) and the control group (N = 566). The main observational endpoints were the incidence of POAF, left ventricular ejection fraction (LVEF) recovery, in-hospital mortality, and short-term mortality. Patients in the sac/val group had a lower incidence of POAF than those in the control group (26/101 vs. 204/566, P = 0.045). Patients in the sac/val group also showed a higher communicative risk for POAF incidence using the Kaplan-Meier survival analysis. In addition, patients in the sac/val group showed better LVEF recovery, with dynamic changes in LVEF superior to that of the control group. The change in LVEF in the sac/val group was 1.78 ± 5.41, compared with -1.19 ± 10.92 in the control group (P = 0.008). This is the first observational study to evaluate the efficacy and safety of sac/val in the prevention and treatment of POAF after cardiac surgery. The results demonstrated that compared with patients who did not receive sac/val treatment, those who received Sac/val treatment showed better POAF control and LVEF recovery. These results should be cautiously interpreted and further confirmed using larger sample sizes and prospective randomized controlled trials.

Anthracyclines-induced cardiotoxicity in patients with early breast cancer carrying germline BRCA1/2 mutation: the BRCAN study.

BRCA1/2 genes play a critical role in genome stability and DNA repair. In animal models, loss of cardiomyocyte-specific BRCA1/2 is associated with DNA damage, apoptosis, cardiac dysfunction, and mortality following anthracycline exposure. However, whether these preclinical findings translate to humans remains unclear. Assess the impact of germline BRCA1/2 (gBRCA1/2) status on anthracyclines-induced cardiotoxicity (AIC) in patients with early breast cancer and no prior anti-HER2 therapy. This single-center retrospective/prospective cohort study focused on early breast cancer patients, treated with anthracycline-based chemotherapy in the neo/adjuvant setting, no prior anti-HER2 therapy, and known gBRCA1/2 status, normal baseline left ventricular ejection fraction (LVEF), and no previous cardiovascular disease. Follow-up assessments involved myocardial dysfunction blood biomarkers (MDBB), transthoracic echocardiography (TTE), and quality of life (QoL) questionnaires. The primary objective was LVEF changes comparing BRCA1/2 mutation carriers (gBRCA1/2m) vs non-carriers (gBRCA1/2wt). Secondary objectives included differences in MDBB and QoL. A total of 137 patients were included (103 gBRCA1/2wt and 34 gBRCA1/2m). Baseline characteristics were similar between groups. Compared to baseline, LVEF% reduction was -4.7[-12.0, 0.0] vs -9.5[-18.0, -5.0] in gBRCA1/2wt vs gBRCA1/2m, (P = .027). After adjusting for confounders, the difference in reduction in LVEF remained statistically significant at -4.5 [95%CI, -8.6, -0.4; P = .032]. No differences between MDBB (C-reactive protein, hsTnI, NT-proBNP, D-Dimer, ST-2, or Galectine-3) or QoL (MLHFQ and EQ5-D index) were detected. gBRCA1/2m patients could represent a higher-risk population for AIC. gBRCA1/2 status should be one of the factors to consider in deciding on adjuvant anthracycline necessity. This population could benefit from a cardio-oncology closer follow-up and cardioprotective strategies.

Abstract 4118387: Artificial Intelligence-Enhanced Echocardiogram Assessment Helps Distinguish Cardiomyopathy from Beat-to-Beat Variation in Atrial Fibrillation

Background: Atrial fibrillation (AF) can be associated with reductions in left ventricular ejection fraction (LVEF) that improve upon conversion of AF to sinus rhythm. Such LVEF changes during AF may be due to LVEF measurement error from beat-to-beat variations related to AF itself. More precise artificial intelligence (AI)-enhanced LVEF assessment could help distinguish between such LVEF “pseudo-reduction” during AF and true cardiomyopathy, thus potentially preventing unnecessary downstream workup and treatment. Methods: Using a transthoracic echocardiogram database at a large academic medical center, we identified all patients whose LVEF fell below 50% while in AF who had subsequent LVEF recovery to over 50% within 90 days after converting from AF to sinus rhythm. For echocardiograms in AF, we compared the clinically assessed LVEF with AI-enhanced LVEF assessment by EchoNet-Dynamic, a validated deep learning algorithm. Results: In our cohort of 84 patients, the mean age was 74 years old, 36.9% were female, and 26.2% non-White. The mean LVEF recovery was 19.3% (95% CI 17.1-21.5%) after converting from AF to sinus rhythm with a mean duration of 27.4 days between the AF and sinus rhythm echocardiograms (Figure 1). For AF echocardiograms, the LVEF when reassessed by deep learning was 8.4% (6.3-10.5%) higher than the original clinical read, resulting in 30.3% of patients being reclassified as no longer having a reduced LVEF less than 50% while in AF. Among these patients with LVEF reductions during AF, 27.4% and 19.0% were given a new or worsened heart failure with reduced ejection fraction (HFrEF) diagnosis, 15.5% underwent ischemic testing, and 17.9% were started on new HFrEF medications. Discussion: LVEF reductions during AF can lead to new HFrEF diagnosis, workup, and treatment. However, such LVEF reductions may be temporary and partially explained by undermeasurement of LVEF during AF. AI-enhanced LVEF assessment may help reduce such measurement errors during AF and thereby prevent overdiagnosis of HFrEF. Further research is needed to understand the clinical significance of true but temporary LVEF reductions during AF.

Abstract 4137113: The Effectiveness of Cardiac Resynchronization Therapy in Patients with Cardiac Sarcoidosis: A Retrospective Analysis

Background: Cardiac sarcoidosis (CS) manifests in a wide range of clinical presentations, including conduction system abnormalities, ventricular arrhythmias, and systolic heart failure. Although cardiac resynchronization therapy (CRT) has shown efficacy in treating select nonischemic cardiomyopathy patients, its specific impact on CS patients remains less explored. This study aimed to evaluate the outcomes of CRT therapy in CS patients, focusing on implantable cardioverter defibrillator (ICD) therapies, heart failure (HF) hospitalizations and mortality. Methods: We retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent device implantation (ICD or Permanent Pacemaker (PPM)) with or without CRT therapy at Johns Hopkins Hospital between 2004 and 2024. Baseline characteristics and echocardiographic parameters were assessed. Heart failure hospitalizations, the frequency of ATP (Anti-Tachycardia Pacing) or ICD shocks, and all-cause mortality were also evaluated as the outcomes. Results: The study included 212 patients (40.1% female, average age 52.8 ± 11.1 years). Eighty-five patients underwent CRT implantation (82 CRT-D and 3 CRT-P), whereas the rest received either an ICD or a PPM without CRT therapy. Most CRT devices (58.82%) were upgrades from an initial PPM or ICD. Over a follow-up of 6.15 ± 4.43 years, 27 (12.74%) patients were hospitalized for heart failure (HF), 86 (40.56%) experienced ATP or ICD shocks, and 17 (8.02%) died. The composite outcome was observed in 103 patients (48.5%), with no significant differences between CRT and non-CRT groups ( P = .51). Survival analysis indicated significantly reduced freedom from HF hospitalizations in the CRT group compared to non-CRT group ( P = .01). However, ATP/ICD shocks did not have a significant difference. CRT recipients showed an improvement in left ventricular ejection fraction (LVEF) from 35.3 ± 12.6% to 38.9 ± 13.6% at 6 months ( P = .01). Non-recipients showed no significant change in LVEF ( P = .43). Conclusions: Over an average six-year follow-up period, CRT upgrade does not appear to affect ATP/ICD shock and mortality in CS patients, although it is associated with significantly higher rates of heart failure (HF) hospitalizations compared to CS patients with an ICD or PPM alone. These findings underscore the complex response of CS patients to CRT, highlighting the need for further research to optimize treatment strategies within this subgroup.

Abstract 4137311: Inhibition of IL-33 by tozorakimab in patients with diabetic kidney disease: Cardiovascular insights from FRONTIER-1

Introduction: Interleukin-33 (IL-33) is a potent mediator of injury-induced local inflammation. Soluble ST2 (sST2), a decoy receptor of IL-33, is a prognostic serum biomarker for heart failure (HF). Here, we evaluated the impact of tozorakimab, an IL-33-neutralizing monoclonal antibody, on sST2-related secondary cardiac endpoints. Methods: FRONTIER-1 was a 24-week phase 2B study (NCT04170543) in patients with diabetic kidney disease (DKD). Key cardiac exclusion criteria were: 1) NYHA Class 3/4; 2) Left ventricular ejection fraction (LVEF) &lt; 40%; 3) B-type natriuretic peptide (BNP) &gt; 200 pg/mL. Local echocardiography (LVEF) was performed at Screening and Week 24. For exploratory analysis, echocardiography recordings were evaluated by a core laboratory. Throughout the study, BNP and sST2 were assessed and adverse events (AE) recorded. Safety and tolerability were evaluated for all dosed participants (Safety Analysis Population, SAP). Results: 573 participants were included in the SAP (139 = placebo / 434 = tozorakimab). Baseline characteristics were balanced across treatment groups. Tozorakimab was generally well tolerated and the incidences of AE, serious AE (SAEs), discontinuations, and death were similar to placebo. In the placebo group, cardiac disorder AE were reported in 6.5%, and SAE in 2.2%. Decline in LVEF of &gt; 10% was seen in 5 participants (4.3%). None developed BNP &gt; 200 pg/mL or clinical signs of HF. 1 participant (0.7%) presented with clinical symptoms of HF (SAE) without significant changes in LVEF or BNP. On tozorakimab, cardiac disorder AE/SAE were less frequent (3.7%/1.8%). Decline in LVEF of &gt; 10% was observed in 31 participants (8.3%), with 3 showing BNP elevation to 200–308 pg/mL. Two of these participants (0.5%) developed clinical signs of HF with LVEF 55%/30% and BNP &lt; 200 pg/mL. No further AE related to HF were reported for tozorakimab. Central analysis of LVEF revealed a substantial variability of site-based measurements indicating LVEF reductions &gt; 10 % in 2 (3.7%) participants on placebo and 6 (2.9%) on tozorakimab. Furthermore, central exploratory analysis demonstrated a slight increase in LVEF from baseline (1.62%, 95% CI: 0.22, 3.03) and a reduction in average E/e' (-0.47, 95% CI: -0.93, -0.01) for tozorakimab, but not placebo. Trends in BNP and sST2 over time were comparable. Conclusion: This study suggests a favorable cardiac safety profile for tozorakimab in patients with DKD. IL-33 inhibition did not elevate serum sST2 significantly.

Abstract 4139196: Long-term effectiveness and safety of mavacamten in a real-world, multi-center, global study: Preliminary results of COLLIGO-HCM from a diverse cohort in the United States

Introduction: The mavaCamten ObservationaL evIdence Global cOnsortium in hypertrophic cardiomyopathy (COLLIGO-HCM; ClinicalTrials.gov ID NCT06372457) is a multinational, multicenter observational research initiative aiming to describe the real-world outcomes of mavacamten for the treatment of obstructive HCM. Aims: Describe the real-world effectiveness and safety of mavacamten, measured by echo measurements and NYHA class. Methods: This retrospective study used data from medical records from two participating HCM centers in the US. Patient-level data was extracted to assess the effectiveness and safety of mavacamten post-treatment initiation through 60 weeks. Patient characteristics and outcomes were described, including echocardiogram measurements, New York Heart Association (NYHA) functional class, and safety. Results: A total of 93 patients were treated with mavacamten (mean age 60.6 ± 13.9 years, 23.7% black, 57.0% female, and 77.4% NYHA class III at baseline) with a mean follow-up of 37.0 ± 28.1 weeks ( Table ). From baseline to week 60, 3 (3.2%) patients experienced temporary treatment discontinuation, and 3 (3.2%) discontinued mavacamten due to left ventricular ejection fraction (LVEF) &lt;50%. By week 12, 77.1% of patients had improved by ≥1 NYHA class. The percentage increased to 89.5% by week 24 and remained stable through week 60. Mean changes from baseline in resting and Valsalva left ventricular outflow tract gradients were 31.8 ± 32.8 and 57.3 ± 47.3 mmHg, respectively, at week 24, and remained similar through week 60. Mean change in LVEF from baseline was 4.1 ± 7.1% at week 12 and remained largely unchanged through week 60 (Figure) . Conclusions: This study demonstrated the early and sustained effectiveness of mavacamten with one of the longest follow-ups to date, in a real-world population with a higher racial diversity and disease burden than those in the clinical trials. This data further substantiates the effectiveness and safety profile of mavacamten.

Abstract 4137996: Effects of Empagliflozin on diuresis in heart failure: Results from the CINNAMON-study and in-vivo experiments

Background and Purpose: Heart failure is associated with renal dysfunction suggesting a pathophysiological link between heart and kidney. Empagliflozin, a SGLT2 inhibitor, showed beneficial effects on both cardiovascular and renal endpoints. However, mechanistically, it is unclear if empagliflozin-dependent kidney protection is mediated via inhibition of tubular SGLT2 or more indirectly via improved cardiac function. We hypothesized that Empagliflozin treatment improves left ventricular ejection fraction (LVEF) independent of diuretic effect of renal SGLT2 inhibition. Methods: We evaluated NTproBNP, hematocrit, hemoglobin and bodyweight in patients with HF with reduced (n=32) and preserved ejection fraction (n=59) after 30 and 180 days (prospective, single-arm CINNAMON-study, DRKS00031101). Furthermore, we conducted transverse aortic constriction (TAC) or sham surgery in C57BL/6J (wildtype, WT) and SGLT2 deficient mice (SGLT2 -/- ). Animals received either Empagliflozin (10 mg/kg bodyweight) or vehicle by daily oral gavage. Water intake and output was evaluated by metabolic cages at 10 weeks and cardiac function by echocardiography. Results: Empagliflozin treatment reduced NT-proBNP levels and increased hematocrit and hemoglobin levels especially in patients with reduced ejection fraction (Fig. A-C). Surprisingly, there was no change in body weight (Fig. D), which would be expected if the diuretic effects were dominant. In mice after 10 weeks, echocardiography confirmed TAC induced pressure-overload, leading to reduced LVEF. Empagliflozin attenuated changes in LVEF (Fig. G) and improved diastolic dysfunction (isovolumetric relaxation time, data not shown). To test if direct inhibition of SGLT2 in the heart and kidney is mechanistically involved, TAC surgery was repeated in SGLT2-deficient mice (SGLT2-KO). In fact, exposure to TAC resulted in comparable reduction of LVEF in SGLT2-KO and Empagliflozin prevented this deterioration similar to WT mice (Fig. G vs. I). Surprisingly, Empagliflozin did not increase drinking and urine volume neither in wildtype nor in SGLT2 deficient mice, suggesting a mechanism of cardioprotection independent of diuretic effects. Conclusion and Outlook: This is the first study investigating the role of SGLT2 in Empagliflozin treated patients and mice with heart failure. Importantly, empagliflozin treatment prevented deterioration of LVEF independent of the presence of SGLT2 and diuresis.

Meta-analysis of the efficacy and impact on cardiac function of sodium-glucose cotransporter 2 inhibitor Empagliflozin in heart failure patients.

Currently, there is no comprehensive systematic review available to comprehensively assess the efficacy and safety of Empagliflozin and other sodium-glucose cotransporter 2 inhibitors in the treatment of heart failure (HF). This study employed a meta-analysis approach to systematically evaluate the therapeutic effects of Empagliflozin in HF patients and its impact on cardiac function. The keywords including "heart failure," "HF," "cardiac failure," "cardiac disease," "Empagliflozin," and "sodium-glucose cotransporter 2 inhibitors" were utilized to search for relevant clinical studies on Empagliflozin in the treatment of HF in various databases, such as China National Knowledge Infrastructure, Wanfang, VIP Chinese Medical Journal Database, PubMed, MEDLINE, Embase, Cochrane Library, Springer, and Science Direct. The studies included patients with HF who received drug treatment. Data on baseline characteristics and posttreatment outcomes, including HF hospitalization (HHF), cardiovascular mortality, all-cause mortality, estimated glomerular filtration rate changes, Kansas City Cardiomyopathy Questionnaire quality of life (QoL) scores, N-terminal pro-B-type natriuretic peptide, left ventricular ejection fraction, hematocrit, and other relevant indicators were collected. Meta-analysis was conducted using RevMan5.3 to analyze the extracted data. A total of 15 studies were included in the final analysis, comprising 36,917 patients with HF. Among them, 18,486 patients were in Empagliflozin group, and 18,431 patients were in control (Ctrl) group. The results of the meta-analysis demonstrated that, relative to Ctrl group, Empagliflozin group showed a substantially lower HHF rate, a substantial improvement in estimated glomerular filtration rate changes, a reduced cardiovascular mortality rate, a higher Kansas City Cardiomyopathy Questionnaire QoL score, increased hematocrit values, reduced N-terminal pro-B-type natriuretic peptide changes, and enhanced left ventricular ejection fraction changes. These findings suggest that remarkable improvements in various outcomes compared to the Ctrl group. The sodium-glucose cotransporter 2 inhibitor Empagliflozin markedly reduces the HHF rate and cardiovascular mortality in HF patients. It also improves patients' QoL, enhances renal function, and increases cardiac function while reducing both, the preload and afterload.