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The role of the beta-adrenergic signaling pathway in heart failure (HF) is pivotal. Early blockade of this pathway with beta-blocker (BB) therapy is recommended as the first-line medication for patients with HF and reduced ejection fraction (HFrEF). Conversely, in patients with severe acute HF (AHF), including those with resolved cardiogenic shock (CS), BB initiation can be hazardous. There are very few data on the management of BB in these situations. The present expert consensus aims to review all published data on the use of BB in patients with severe decompensated AHF, with or without hemodynamic compromise, and proposes an expert-recommended practical algorithm for the prescription and monitoring of BB therapy in critical settings.

BackgroundAcute ST-elevation myocardial infarction (STEMI) can lead to adverse cardiac remodeling, resulting in left ventricular systolic dysfunction (LVSd) and heart failure. Epigenetic regulators, such as microRNAs, may be involved in the physiopathology of LVSd.ObjectiveThis study explored microRNAs in peripheral blood mononuclear cells (PBMC) of post-myocardial infarction patients with LVSd.MethodsPost-STEMI patients were grouped as having (LVSd, n = 9) or not LVSd (non-LVSd, n = 16). The expression of 61 microRNAs was analyzed in PBMC by RT-qPCR and the differentially expressed microRNAs were identified. Principal Component Analysis stratified the microRNAs based on the development of dysfunction. Predictive variables of LVSd were investigated through logistic regression analysis. A system biology approach was used to explore the regulatory molecular network of the disease and an enrichment analysis was performed.ResultsThe let-7b-5p (AUC: 0.807; 95% CI: 0.63–0.98; p = 0.013), miR-125a-3p (AUC: 0.800; 95% CI: 0.61–0.99; p = 0.036) and miR-326 (AUC: 0.783; 95% CI: 0.54–1.00; p = 0.028) were upregulated in LVSd (p

ObjectivesThis study sought to noninvasively determine myocardial iron levels in HIV-1-infected patients using CMR and explore the association between T2* values and mild left ventricular systolic dysfunction (LVSD).MethodsThis prospective study was conducted from June 2019 to July 2021. HIV-1-infected adults and healthy controls were consecutively enrolled for CMR exam. CMR exam included the assessment of myocardium iron content (T2*), cardiac function (cine), inflammation (T2), and fibrosis (through extracellular volume fraction [ECV] and late gadolinium enhancement [LGE]) measurements. Mild LVSD is defined as a left ventricular ejection fraction (LVEF) between 40% and 49%.ResultsOf 47 HIV-1-infected patients enrolled, 12 were diagnosed with mild LVSD (HIV-1+/LEVF+) and 35 were diagnosed with preserved LV function (HIV-1+/LEVF−). Compared with healthy controls, HIV-1-infected patients displayed higher T2*, T1, T2, ECV values and lower global circumferential strain (GCS) and global radial strain (GRS) (all P 26 ms) and mild LVSD remained significant after adjusting for the established univariate predictors (ECV >32.9%, T1 values >1336 ms) of mild LVSD (odds ratio [OR], 10.153; 95% confidence interval [CI] 1.565–65.878, P = 0.015).ConclusionsMyocardial T2* values were elevated in HIV-1-infected patients, supporting the notion that ID was associated with mild LVSD. Our findings highlight the potential for ID in HIV-1-infected patients as an auxiliary biomarker to monitor the course of LVSD.

BackgroundLeft ventricular systolic dysfunction (LVSD) characterized by a reduced left ventricular ejection fraction (LVEF) is associated with adverse patient outcomes. We aimed to build a deep neural network (DNN)-based model using standard 12-lead electrocardiogram (ECG) to screen for LVSD and stratify patient prognosis.MethodsThis retrospective chart review study was conducted using data from consecutive adults who underwent ECG examinations at Chang Gung Memorial Hospital in Taiwan between October 2007 and December 2019. DNN models were developed to recognize LVSD, defined as LVEF

PurposeAmyloid overload and microcirculation impairment are both detrimental to left ventricular (LV) systolic function, while it is not clear which factor dominates LV functional remodeling in patients with cardiac amyloidosis (CA). The purpose of this study was to investigate the major factor of LV systolic dysfunction using cardiac magnetic resonance imaging.Materials and methodsForty CA patients and 20 healthy controls were included in this study. The CA group was divided into two subgroups by the left ventricular ejection fraction (LVEF): patients with reduced LVEF (LVEF

IntroductionWe sought to investigate the prognostic impact of incident left ventricular (LV) systolic dysfunction at the chronic phase of acute myocardial infarction (AMI).Materials and methodsAmong 2,266 consecutive patients admitted for AMI, 1,330 patients with LV ejection fraction (LVEF) ≥ 40% during hospitalization who had LVEF data at 6 months after AMI were analyzed. Patients were divided into three subgroups based on LVEF at 6 months: reduced-LVEF (

BackgroundCoronary perfusion pressure (CPP) and coronary artery stenosis are responsible for myocardial perfusion. However, how CPP-related survival outcome affects revascularization is unclear.ObjectiveThe aim of this study is to investigate the prognostic role of CPP in patients with left ventricular systolic dysfunction (LVSD) undergoing percutaneous coronary intervention (PCI) with complete revascularization (CR) or reasonable incomplete revascularization (RIR).MethodsWe retrospectively screened 6,076 consecutive patients in a registry. The residual synergy between percutaneous coronary intervention with Taxus and cardiac surgery (SYNTAX) score (rSS) was used to define CR (rSS = 0) and RIR (0 42 mmHg. Moreover, 101 pairs of RIR and CR were present in patients with CPP ≤ 42 mmHg. In patients with CPP > 42 mmHg, RIR was not significantly different from CR in long-term mortality [hazard ratio (HR) 1.20; 95% confidence interval (CI):0.70–2.07; p = 0.513]; However, in patients with CPP≤42 mmHg, RIR had a significantly higher mortality risk than CR (HR 2.39; 95% CI: 1.27–4.50; p = 0.007).ConclusionsThe CPP had a risk stratification role in selecting different revascularization strategies in patients with LVSD. When patients with LVSD had CPP > 42 mmHg, RIR was equivalent to CR in survival. However, when patients with LVSD had CPP ≤ 42 mmHg, RIR had a significantly higher mortality risk than CR.

Background: Few studies have characterized electrocardiography (ECG) patterns correlated with left ventricular (LV) systolic dysfunction in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS).Objectives: This study aims to develop ECG pattern-derived scores to predict LV systolic dysfunction in NSTE-ACS patients.Methods: A total of 466 patients with NSTE-ACS were retrospectively enrolled. LV ejection fraction (LVEF) was assessed by echocardiography within 72 h after the first triage ECG acquisition; there was no coronary intervention in between. ECG score was developed to predict LVEF < 40%. Performance of LVEF, the Global Registry of Acute Coronary Events (GRACE), Thrombolysis in Myocardial Infarction (TIMI) and ECG scores to predict 24-month all-cause mortality were analyzed. Subgroups with varying LVEF, GRACE and TIMI scores were stratified by ECG score to identify patients at high risk of mortality.Results: LVEF < 40% was present in 20% of patients. We developed the PQRST score by multivariate logistic regression, including poor R wave progression, QRS duration > 110 ms, heart rate > 100 beats per min, and ST-segment depression ≥ 1 mm in ≥ 2 contiguous leads, ranging from 0 to 6.5. The score had an area under the curve (AUC) of 0.824 in the derivation cohort and 0.899 in the validation cohort for discriminating LVEF < 40%. A PQRST score ≥ 3 could stratify high-risk patients with LVEF ≥ 40%, GRACE score > 140, or TIMI score ≥ 3 regarding 24-month all-cause mortality.Conclusions: The PQRST score could predict LVEF < 40% in NSTE-ACS patients and identify patients at high risk of mortality in the subgroups of patients with LVEF ≥ 40%, GRACE score > 140 or TIMI score ≥ 3.

Background:The prognostic impact and optimal treatment of left ventricular systolic dysfunction in patients with moderate aortic regurgitation (AR) remain unknown. We aimed to assess the prognostic value of left ventricular ejection fraction (LVEF) in patients with moderate AR and explore the potential benefits of aortic valve intervention (AVI).Methods:In total, 1,211 consecutive patients with moderate AR (jet width, 25–64% of LV outflow tract; vena contracta, 0.3–0.6 cm; regurgitant volume, 30–59 mL/beat; regurgitant fraction, 30–49%; effective regurgitation orifice, 0.10–0.29 cm2) prospectively registered between April and June 2018 at 46 academic hospitals were included. The primary outcome was a composite of death or hospitalization for heart failure (HHF). The optimal LVEF threshold for predicting the primary outcome was determined through the penalized spline shape and maximally selected rank statistics.Results:During the 2-year follow-up, 125 deaths or HHF occurred. In the penalized splines, the relative hazard of death or HHF monotonically increased with decreasing LVEF. In the multivariate analysis, LVEF ≤55% was identified as the best threshold for independently predicting death or HHF under medical treatment (adjusted hazard ratio [HR]: 2.18; 95% confidence interval [CI] 1.38–3.42; P = 0.001), with substantial incremental values (integrated discrimination improvement index = 0.018, P = 0.030; net reclassification improvement index = 0.225, P = 0.006; likelihood ratio test P < 0.001). Among patients with LVEF 35–55%, AVI within 6 months of diagnosis was associated with a reduced risk of death or HHF compared with medical treatment alone (adjusted HR: 0.15; 95% CI: 0.04–0.50; P = 0.002), whereas this benefit was markedly attenuated when LVEF was ≤35% (adjusted HR: 0.65; 95% CI: 0.21–1.97; P = 0.441, P-interaction = 0.010) or >55% (adjusted HR: 0.40; 95% CI: 0.14–1.15; P = 0.089, P-interaction = 0.723).Conclusions:LVEF is an independent and incremental prognostic factor in patients with moderate AR, with LVEF ≤55% being a robust marker of poor prognosis. Patients with LVEF 35–55% may benefit from early surgical correction of moderate AR. Further studies are warranted to validate our findings in a randomized setting.Registration:China Valvular Heart Disease Study (China-VHD study, NCT03484806); clinicaltrials.gov/ct2/show/NCT03484806.

The increasing incidence of stress-induced cardiomyopathy is due to the complexities of our modern-day lives, which constantly elicit stress responses. Herein, we aimed to explore the therapeutic potential of Amlexanox and Forskolin in promoting the recovery from stress-induced cardiomyopathy. Isoproterenol-induced cardiomyopathy (ICM) models were made, and the following treatment interventions were administered: 5% v/v DMSO as a placebo, Amlexanox (2.5 mg/100 g/day) treatment, Forskolin (0.5 mg/100 g/day), and Amlexanox and Forskolin combination, at their respective aforementioned dosages. The effects of Amlexanox and Forskolin treatment on ICM models were assessed by eletrocardiography and echocardiography. Also, using histological analysis and ELISA, their impact on myocardial architecture and inflammation were ascertained. ICM mice had excessive myocardial fibrosis, hypertrophy, and aggravated LVSDs which were accompanied by massive CD86+ inflammatory cells infiltration. Amlexanox treatment attenuated the myocardial hypertrophy, fibrosis, and inflammation and also slightly improved systolic functions. Meanwhile, forskolin treatment resulted in arrhythmias but significantly enhanced the resolution of myocardial fibrosis and inflammation. Intriguingly, Amlexanox and Forskolin combination demonstrated the most potency at promoting the recovery of the ICM from LVSD by attenuating maladaptive myocardial hypertrophy, fibrosis, and inflammatory responses. Our findings highlight the Amlexanox and Forskolin combination as a potential therapeutic intervention for enhancing cardiac function recovery from stress-induced cardiomyopathy by promoting the resolution of maladaptive cardiac remodeling.

Background: Neprilysin inhibition has demonstrated impressive benefits in heart failure treatment, and is the current focus of interest in cardiovascular (CV) and kidney diseases. However, the role of circulating neprilysin as a biomarker for CV events is unclear in hemodialysis (HD) patients.Methods: A total of 439 HD patients from the K-cohort were enrolled from June 2016 to April 2019. The plasma neprilysin level and echocardiographic findings at baseline were examined. The patients were prospectively followed up to assess the primary endpoint (composite of CV events and cardiac events).Results: Plasma neprilysin level was positively correlated with left ventricular (LV) mass index, LV end-systolic volume, and LV end-diastolic volume. Multivariate linear regression analysis revealed that neprilysin level was negatively correlated with LV ejection fraction (β = −2.14; p = 0.013). The cumulative event rate of the composite of CV events was significantly greater in neprilysin tertile 3 (p = 0.049). Neprilysin tertile 3 was also associated with an increased cumulative event rate of cardiac events (p = 0.016). In Cox regression analysis, neprilysin tertile 3 was associated with a 2.61-fold risk for the composite of CV events [95% confidence interval (CI), 1.37–4.97] and a 2.72-fold risk for cardiac events (95% CI, 1.33–5.56) after adjustment for multiple variables.Conclusions: Higher circulating neprilysin levels independently predicted the composite of CV events and cardiac events in HD patients. The results of this study suggest the importance of future studies on the effect of neprilysin inhibition in reducing CV events.

Background: The number of coronary chronic total occlusion (CTO) patients with left ventricular (LV) systolic dysfunction is significant, but the clinical outcomes of these patients are rarely reported. The present retrospective cohort study aimed to investigate the long-term outcomes of successful recanalization vs. optimal medical therapy (MT) for CTOs in patients with preserved and impaired LV systolic function.Methods: A total of 1,895 patients with CTOs were stratified according to LV function. Of these, 1,420 patients (74.9%) with LV ejection fraction (LVEF) >45% and 475 patients (25.1%) with LVEF ≤45% were treated with optimal MT or successful CTO percutaneous coronary intervention (PCI). A 1:1 propensity score matching (PSM) was conducted to reduce the impact of potential confounding on the outcomes. The primary outcome was the frequency of major adverse cardiac events (MACEs).Results: Throughout a 2.6-year follow-up and after adjusting for confounders, among patients with preserved LV function, successful CTO PCI was associated with reduced incidence of MACE (14.2 vs. 23.9%, adjusted HR 0.63, 95% CI 0.48–0.83, p = 0.001) compared to MT. There was no significant difference in MACE occurrence (29.6 vs. 28.9%, adjusted HR 1.05, 95% CI: 0.71–1.56, p = 0.792) between successful recanalization and MT in patients with LV systolic dysfunction. The primary outcome among patients with impaired and preserved LV systolic function after PSM was similar to that from earlier findings before PSM was conducted. A significant interaction between LV function and therapeutic strategy for MACE was observed (interaction p = 0.038).Conclusions: Compared to MT alone for management of patients with CTOs, successful CTO PCI may reduce the risk of MACE in patients with preserved LV systolic function, but not in patients with LV dysfunction.

Objective: Left ventricular systolic dysfunction (LVSD) after ST-segment elevation myocardial infarction (STEMI) is associated with poor outcome. Trimethylamine N-oxide (TMAO), a gut metabolite, is linked to cardiovascular diseases but its relationship with LVSD after STEMI remains unclear. The present study therefore aimed to investigate the relationship between TMAO and LVSD at 30 days after a first anterior STEMI.Methods: This was a sub-study from the OCTAMI (Optical Coherence Tomography Examination in Acute Myocardial Infarction) registry. Eligible patients were included in current study if they: (1) presented with a first anterior STEMI; (2) had available baseline TMAO concentration; (3) completed a cardiovascular magnetic resonance examination at 30 days after STEMI. LVSD was defined as left ventricular ejection fraction < 50%. Associations between TMAO and left ventricular ejection fraction, infarct size and left ventricular global strain were examined.Results: In total, 78 patients were included in final analysis. Overall, TMAO was moderately associated with peak cTnI (r = 0.27, p = 0.01), age (r = 0.34, p < 0.01), and estimated glomerular filtration rate (r = −0.30, p < 0.01). At 30-day follow-up, 41 patients were in the LVSD group and 37 in the non-LVSD group. Baseline TMAO levels were not significantly different between the two groups (LVSD vs. non-LVSD: median 1.9 μM, 25−75th percentiles 1.5–3.3 μM vs. median 1.9 μM, 25−75th percentiles 1.5–2.7 μM; p = 0.46). Linear regression analyses showed that TMAO was not associated with left ventricular ejection fraction, infarct size or left ventricular global strain at 30 days (all p > 0.05).Conclusions: TMAO was not significantly correlated with 30-day LVSD in patients with a first anterior STEMI after primary revascularization.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03593928.

The role of the beta-adrenergic signaling pathway in heart failure (HF) is pivotal. Early blockade of this pathway with beta-blocker (BB) therapy is recommended as the first-line medication for patients with HF and reduced ejection fraction (HFrEF). Conversely, in patients with severe acute HF (AHF), including those with resolved cardiogenic shock (CS), BB initiation can be hazardous. There are very few data on the management of BB in these situations. The present expert consensus aims to review all published data on the use of BB in patients with severe decompensated AHF, with or without hemodynamic compromise, and proposes an expert-recommended practical algorithm for the prescription and monitoring of BB therapy in critical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 Schurtz, Mewton, Lemesle, Delmas, Levy, Puymirat, Aissaoui, Bauer, Gerbaud, Henry, Bonello, Bochaton, Bonnefoy, Roubille and Lamblin.)

Background: Acute ST-elevation myocardial infarction (STEMI) can lead to adverse cardiac remodeling, resulting in left ventricular systolic dysfunction (LVSd) and heart failure. Epigenetic regulators, such as microRNAs, may be involved in the physiopathology of LVSd., Objective: This study explored microRNAs in peripheral blood mononuclear cells (PBMC) of post-myocardial infarction patients with LVSd., Methods: Post-STEMI patients were grouped as having (LVSd, n  = 9) or not LVSd (non-LVSd, n  = 16). The expression of 61 microRNAs was analyzed in PBMC by RT-qPCR and the differentially expressed microRNAs were identified. Principal Component Analysis stratified the microRNAs based on the development of dysfunction. Predictive variables of LVSd were investigated through logistic regression analysis. A system biology approach was used to explore the regulatory molecular network of the disease and an enrichment analysis was performed., Results: The let-7b-5p (AUC: 0.807; 95% CI: 0.63-0.98; p  = 0.013), miR-125a-3p (AUC: 0.800; 95% CI: 0.61-0.99; p  = 0.036) and miR-326 (AUC: 0.783; 95% CI: 0.54-1.00; p  = 0.028) were upregulated in LVSd ( p  < 0.05) and discriminated LVSd from non-LVSd. Multivariate logistic regression analysis showed let-7b-5p (OR: 16.00; 95% CI: 1.54-166.05; p  = 0.020) and miR-326 (OR: 28.00; 95% CI: 2.42-323.70; p  = 0.008) as predictors of LVSd. The enrichment analysis revealed association of the targets of these three microRNAs with immunological response, cell-cell adhesion, and cardiac changes., Conclusion: LVSd alters the expression of let-7b-5p, miR-326, and miR-125a-3p in PBMC from post-STEMI, indicating their potential involvement in the cardiac dysfunction physiopathology and highlighting these miRNAs as possible LVSd biomarkers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Dantas-Komatsu, Cruz, Freire, Diniz, Bortolin, Cabral-Marques, Souza, Hirata, Hirata, Reis, Jurisica, Silbiger and Luchessi.)

Objectives: This study sought to noninvasively determine myocardial iron levels in HIV-1-infected patients using CMR and explore the association between T2* values and mild left ventricular systolic dysfunction (LVSD)., Methods: This prospective study was conducted from June 2019 to July 2021. HIV-1-infected adults and healthy controls were consecutively enrolled for CMR exam. CMR exam included the assessment of myocardium iron content (T2*), cardiac function (cine), inflammation (T2), and fibrosis (through extracellular volume fraction [ECV] and late gadolinium enhancement [LGE]) measurements. Mild LVSD is defined as a left ventricular ejection fraction (LVEF) between 40% and 49%., Results: Of 47 HIV-1-infected patients enrolled, 12 were diagnosed with mild LVSD (HIV-1+/LEVF+) and 35 were diagnosed with preserved LV function (HIV-1+/LEVF-). Compared with healthy controls, HIV-1-infected patients displayed higher T2*, T1, T2, ECV values and lower global circumferential strain (GCS) and global radial strain (GRS) (all P  < 0.05). However, between patients with and without mild LVSD, only the T2* values and ECV (all P <0.05) were different. The association between increased T2* values (>26 ms) and mild LVSD remained significant after adjusting for the established univariate predictors (ECV >32.9%, T1 values >1336 ms) of mild LVSD (odds ratio [OR], 10.153; 95% confidence interval [CI] 1.565-65.878, P  = 0.015)., Conclusions: Myocardial T2* values were elevated in HIV-1-infected patients, supporting the notion that ID was associated with mild LVSD. Our findings highlight the potential for ID in HIV-1-infected patients as an auxiliary biomarker to monitor the course of LVSD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Yan, Li, Zhang, Zhang, Yang, Zhang and Li.)

Background: Left ventricular systolic dysfunction (LVSD) characterized by a reduced left ventricular ejection fraction (LVEF) is associated with adverse patient outcomes. We aimed to build a deep neural network (DNN)-based model using standard 12-lead electrocardiogram (ECG) to screen for LVSD and stratify patient prognosis., Methods: This retrospective chart review study was conducted using data from consecutive adults who underwent ECG examinations at Chang Gung Memorial Hospital in Taiwan between October 2007 and December 2019. DNN models were developed to recognize LVSD, defined as LVEF <40%, using original ECG signals or transformed images from 190,359 patients with paired ECG and echocardiogram within 14 days. The 190,359 patients were divided into a training set of 133,225 and a validation set of 57,134. The accuracy of recognizing LVSD and subsequent mortality predictions were tested using ECGs from 190,316 patients with paired data. Of these 190,316 patients, we further selected 49,564 patients with multiple echocardiographic data to predict LVSD incidence. We additionally used data from 1,194,982 patients who underwent ECG only to assess mortality prognostication. External validation was performed using data of 91,425 patients from Tri-Service General Hospital, Taiwan., Results: The mean age of patients in the testing dataset was 63.7 ± 16.3 years (46.3% women), and 8,216 patients (4.3%) had LVSD. The median follow-up period was 3.9 years (interquartile range 1.5-7.9 years). The area under the receiver-operating characteristic curve (AUROC), sensitivity, and specificity of the signal-based DNN (DNN-signal) to identify LVSD were 0.95, 0.91, and 0.86, respectively. DNN signal-predicted LVSD was associated with age- and sex-adjusted hazard ratios (HRs) of 2.57 (95% confidence interval [CI], 2.53-2.62) for all-cause mortality and 6.09 (5.83-6.37) for cardiovascular mortality. In patients with multiple echocardiograms, a positive DNN prediction in patients with preserved LVEF was associated with an adjusted HR (95% CI) of 8.33 (7.71 to 9.00) for incident LVSD. Signal- and image-based DNNs performed equally well in the primary and additional datasets., Conclusion: Using DNNs, ECG becomes a low-cost, clinically feasible tool to screen LVSD and facilitate accurate prognostication., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Hsu, Liu, Lin, Tsai, Chen, Chang, Liu, Lee, Wo, Chou, Wang, Wen and Kuo.)

Purpose: Amyloid overload and microcirculation impairment are both detrimental to left ventricular (LV) systolic function, while it is not clear which factor dominates LV functional remodeling in patients with cardiac amyloidosis (CA). The purpose of this study was to investigate the major factor of LV systolic dysfunction using cardiac magnetic resonance imaging., Materials and Methods: Forty CA patients and 20 healthy controls were included in this study. The CA group was divided into two subgroups by the left ventricular ejection fraction (LVEF): patients with reduced LVEF (LVEF < 50%, rLVEF), and patients with preserved LVEF (LVEF ≥ 50%, pLVEF). The scanning sequences included cine, native and post-contrast T1 mapping, rest first-pass perfusion and late gadolinium enhancement. Perfusion and mapping parameters were compared among the three groups. Correlation analysis was performed to evaluate the relationship between LVEF and mapping parameters, as well as the relationship between LVEF and perfusion parameters., Results: Remarkably higher native T1 value was observed in the rLVEF patients than the pLVEF patients (1442.2 ± 85.8 ms vs. 1407.0 ± 93.9 ms, adjusted p  = 0.001). The pLVEF patients showed significantly lower slope dividing baseline signal intensity (slope%BL; rLVEF vs. pLVEF, 55.1 ± 31.0 vs. 46.2 ± 22.3, adjusted p  = 0.001) and a lower maximal signal intensity subtracting baseline signal intensity (MaxSI-BL; rLVEF vs. pLVEF, 43.5 ± 23.9 vs. 37.0 ± 18.6, adjusted p  = 0.003) compared to the rLVEF patients. CA patients required more time to reach the maximal signal intensity than the controls did (all adjusted p  < 0.01). There was no significant correlation between LVEF and first-pass perfusion parameters, while significant negative correlation was observed between LVEF and native T1 ( r  = -0.434, p  = 0.005) in CA patients., Conclusion: Amyloid overload in the myocardial interstitium may be the major factor of LV systolic dysfunction in CA patients, other than microcirculation impairment., Competing Interests: XZ is employed by Siemens Healthineers Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lu, Zhao, Qiao, Yang, Tang, Zhou, Huang and Xia.)

Introduction: We sought to investigate the prognostic impact of incident left ventricular (LV) systolic dysfunction at the chronic phase of acute myocardial infarction (AMI)., Materials and Methods: Among 2,266 consecutive patients admitted for AMI, 1,330 patients with LV ejection fraction (LVEF) ≥ 40% during hospitalization who had LVEF data at 6 months after AMI were analyzed. Patients were divided into three subgroups based on LVEF at 6 months: reduced-LVEF (<40%), mid-range-LVEF (≥ 40% and < 50%) and preserved-LVEF (≥ 50%). Occurrence of a composite of hospitalization for heart failure or cardiovascular death after 6 months of AMI was the primary endpoint. The prognostic impact of LVEF at 6 months was assessed with a multivariate-adjusted Cox model., Results: Overall, the mean patient age was 67.5 ± 11.9 years, and LVEF during initial hospitalization was 59.4 ± 9.1%. The median (interquartile range) duration of follow-up was 3.0 (1.5-4.8) years, and the primary endpoint occurred in 35/1330 (2.6%) patients (13/69 [18.8%] in the reduced-LVEF, 9/265 [3.4%] in the mid-range-LVEF, and 13/996 [1.3%] in the preserved-LVEF category). The adjusted hazard ratio for the primary endpoint in the reduced-LVEF vs. mid-range-LVEF category and in the reduced-LVEF vs. preserved-LVEF category was 4.71 (95% confidence interval [CI], 1.83 to 12.13; p < 0.001) and 14.37 (95% CI, 5.38 to 38.36; p < 0.001), respectively., Conclusion: Incident LV systolic dysfunction at the chronic phase after AMI was significantly associated with long-term adverse outcomes. Even in AMI survivors without LV systolic dysfunction at the time of AMI, post-AMI reassessment and careful monitoring of LVEF are required to identify patients at risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yoshioka, Tanaka, Watanabe, Nishihira, Natsuaki, Kawaguchi, Shibata and Node.)

Background: Coronary perfusion pressure (CPP) and coronary artery stenosis are responsible for myocardial perfusion. However, how CPP-related survival outcome affects revascularization is unclear., Objective: The aim of this study is to investigate the prognostic role of CPP in patients with left ventricular systolic dysfunction (LVSD) undergoing percutaneous coronary intervention (PCI) with complete revascularization (CR) or reasonable incomplete revascularization (RIR)., Methods: We retrospectively screened 6,076 consecutive patients in a registry. The residual synergy between percutaneous coronary intervention with Taxus and cardiac surgery (SYNTAX) score (rSS) was used to define CR (rSS = 0) and RIR (0 42 mmHg. Moreover, 101 pairs of RIR and CR were present in patients with CPP ≤ 42 mmHg. In patients with CPP > 42 mmHg, RIR was not significantly different from CR in long-term mortality [hazard ratio (HR) 1.20; 95% confidence interval (CI):0.70-2.07; p = 0.513]; However, in patients with CPP≤42 mmHg, RIR had a significantly higher mortality risk than CR (HR 2.39; 95% CI: 1.27-4.50; p = 0.007)., Conclusions: The CPP had a risk stratification role in selecting different revascularization strategies in patients with LVSD. When patients with LVSD had CPP > 42 mmHg, RIR was equivalent to CR in survival. However, when patients with LVSD had CPP ≤ 42 mmHg, RIR had a significantly higher mortality risk than CR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hsieh, Chen, Chen, Lee, Ho, Yeh, Huang, Lu, Chang, Wang, Chang and Hsieh.)

Background: The prognostic impact and optimal treatment of left ventricular systolic dysfunction in patients with moderate aortic regurgitation (AR) remain unknown. We aimed to assess the prognostic value of left ventricular ejection fraction (LVEF) in patients with moderate AR and explore the potential benefits of aortic valve intervention (AVI)., Methods: In total, 1,211 consecutive patients with moderate AR (jet width, 25-64% of LV outflow tract; vena contracta, 0.3-0.6 cm; regurgitant volume, 30-59 mL/beat; regurgitant fraction, 30-49%; effective regurgitation orifice, 0.10-0.29 cm 2 ) prospectively registered between April and June 2018 at 46 academic hospitals were included. The primary outcome was a composite of death or hospitalization for heart failure (HHF). The optimal LVEF threshold for predicting the primary outcome was determined through the penalized spline shape and maximally selected rank statistics., Results: During the 2-year follow-up, 125 deaths or HHF occurred. In the penalized splines, the relative hazard of death or HHF monotonically increased with decreasing LVEF. In the multivariate analysis, LVEF ≤55% was identified as the best threshold for independently predicting death or HHF under medical treatment (adjusted hazard ratio [HR]: 2.18; 95% confidence interval [CI] 1.38-3.42; P = 0.001), with substantial incremental values (integrated discrimination improvement index = 0.018, P = 0.030; net reclassification improvement index = 0.225, P = 0.006; likelihood ratio test P < 0.001). Among patients with LVEF 35-55%, AVI within 6 months of diagnosis was associated with a reduced risk of death or HHF compared with medical treatment alone (adjusted HR: 0.15; 95% CI: 0.04-0.50; P = 0.002), whereas this benefit was markedly attenuated when LVEF was ≤35% (adjusted HR: 0.65; 95% CI: 0.21-1.97; P = 0.441, P-interactio n = 0.010) or >55% (adjusted HR: 0.40; 95% CI: 0.14-1.15; P = 0.089, P-interactio n = 0.723)., Conclusions: LVEF is an independent and incremental prognostic factor in patients with moderate AR, with LVEF ≤55% being a robust marker of poor prognosis. Patients with LVEF 35-55% may benefit from early surgical correction of moderate AR. Further studies are warranted to validate our findings in a randomized setting., Registration: China Valvular Heart Disease Study (China-VHD study, NCT03484806); clinicaltrials.gov/ct2/show/NCT03484806., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflictof interest., (Copyright © 2022 Zhao, Zhang, Ye, Li, Liu, Zhao, Zhao, Wang, Yu, Zhang, Duan, Wang, Lv, Guo, Zhao, Gao, Xu and Wu.)

Background: Few studies have characterized electrocardiography (ECG) patterns correlated with left ventricular (LV) systolic dysfunction in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS). Objectives: This study aims to develop ECG pattern-derived scores to predict LV systolic dysfunction in NSTE-ACS patients. Methods: A total of 466 patients with NSTE-ACS were retrospectively enrolled. LV ejection fraction (LVEF) was assessed by echocardiography within 72 h after the first triage ECG acquisition; there was no coronary intervention in between. ECG score was developed to predict LVEF < 40%. Performance of LVEF, the Global Registry of Acute Coronary Events (GRACE), Thrombolysis in Myocardial Infarction (TIMI) and ECG scores to predict 24-month all-cause mortality were analyzed. Subgroups with varying LVEF, GRACE and TIMI scores were stratified by ECG score to identify patients at high risk of mortality. Results: LVEF < 40% was present in 20% of patients. We developed the PQRST score by multivariate logistic regression, including p oor R wave progression, Q RS duration > 110 ms, heart r ate > 100 beats per min, and ST- segment depression ≥ 1 mm in ≥ 2 contiguous leads, ranging from 0 to 6.5. The score had an area under the curve (AUC) of 0.824 in the derivation cohort and 0.899 in the validation cohort for discriminating LVEF < 40%. A PQRST score ≥ 3 could stratify high-risk patients with LVEF ≥ 40%, GRACE score > 140, or TIMI score ≥ 3 regarding 24-month all-cause mortality. Conclusions: The PQRST score could predict LVEF < 40% in NSTE-ACS patients and identify patients at high risk of mortality in the subgroups of patients with LVEF ≥ 40%, GRACE score > 140 or TIMI score ≥ 3., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Hsiung, Yin, Tsao, Lai and Huang.)

The increasing incidence of stress-induced cardiomyopathy is due to the complexities of our modern-day lives, which constantly elicit stress responses. Herein, we aimed to explore the therapeutic potential of Amlexanox and Forskolin in promoting the recovery from stress-induced cardiomyopathy. Isoproterenol-induced cardiomyopathy (ICM) models were made, and the following treatment interventions were administered: 5% v/v DMSO as a placebo, Amlexanox (2.5 mg/100 g/day) treatment, Forskolin (0.5 mg/100 g/day), and Amlexanox and Forskolin combination, at their respective aforementioned dosages. The effects of Amlexanox and Forskolin treatment on ICM models were assessed by eletrocardiography and echocardiography. Also, using histological analysis and ELISA, their impact on myocardial architecture and inflammation were ascertained. ICM mice had excessive myocardial fibrosis, hypertrophy, and aggravated LVSDs which were accompanied by massive CD86+ inflammatory cells infiltration. Amlexanox treatment attenuated the myocardial hypertrophy, fibrosis, and inflammation and also slightly improved systolic functions. Meanwhile, forskolin treatment resulted in arrhythmias but significantly enhanced the resolution of myocardial fibrosis and inflammation. Intriguingly, Amlexanox and Forskolin combination demonstrated the most potency at promoting the recovery of the ICM from LVSD by attenuating maladaptive myocardial hypertrophy, fibrosis, and inflammatory responses. Our findings highlight the Amlexanox and Forskolin combination as a potential therapeutic intervention for enhancing cardiac function recovery from stress-induced cardiomyopathy by promoting the resolution of maladaptive cardiac remodeling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Adzika, Hou, Adekunle, Rizvi, Adu-Amankwaah, Shang, Li, Deng, Mprah, Ndzie Noah and Sun.)

Background: Neprilysin inhibition has demonstrated impressive benefits in heart failure treatment, and is the current focus of interest in cardiovascular (CV) and kidney diseases. However, the role of circulating neprilysin as a biomarker for CV events is unclear in hemodialysis (HD) patients. Methods: A total of 439 HD patients from the K-cohort were enrolled from June 2016 to April 2019. The plasma neprilysin level and echocardiographic findings at baseline were examined. The patients were prospectively followed up to assess the primary endpoint (composite of CV events and cardiac events). Results: Plasma neprilysin level was positively correlated with left ventricular (LV) mass index, LV end-systolic volume, and LV end-diastolic volume. Multivariate linear regression analysis revealed that neprilysin level was negatively correlated with LV ejection fraction (β = -2.14; p = 0.013). The cumulative event rate of the composite of CV events was significantly greater in neprilysin tertile 3 ( p = 0.049). Neprilysin tertile 3 was also associated with an increased cumulative event rate of cardiac events ( p = 0.016). In Cox regression analysis, neprilysin tertile 3 was associated with a 2.61-fold risk for the composite of CV events [95% confidence interval (CI), 1.37-4.97] and a 2.72-fold risk for cardiac events (95% CI, 1.33-5.56) after adjustment for multiple variables. Conclusions: Higher circulating neprilysin levels independently predicted the composite of CV events and cardiac events in HD patients. The results of this study suggest the importance of future studies on the effect of neprilysin inhibition in reducing CV events., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hwang, Kim, Kim, Lee, Lee, Ahn, Moon, Lee, Ko and Jeong.)

Background: The number of coronary chronic total occlusion (CTO) patients with left ventricular (LV) systolic dysfunction is significant, but the clinical outcomes of these patients are rarely reported. The present retrospective cohort study aimed to investigate the long-term outcomes of successful recanalization vs. optimal medical therapy (MT) for CTOs in patients with preserved and impaired LV systolic function. Methods: A total of 1,895 patients with CTOs were stratified according to LV function. Of these, 1,420 patients (74.9%) with LV ejection fraction (LVEF) >45% and 475 patients (25.1%) with LVEF ≤45% were treated with optimal MT or successful CTO percutaneous coronary intervention (PCI). A 1:1 propensity score matching (PSM) was conducted to reduce the impact of potential confounding on the outcomes. The primary outcome was the frequency of major adverse cardiac events (MACEs). Results: Throughout a 2.6-year follow-up and after adjusting for confounders, among patients with preserved LV function, successful CTO PCI was associated with reduced incidence of MACE (14.2 vs. 23.9%, adjusted HR 0.63, 95% CI 0.48-0.83, p = 0.001) compared to MT. There was no significant difference in MACE occurrence (29.6 vs. 28.9%, adjusted HR 1.05, 95% CI: 0.71-1.56, p = 0.792) between successful recanalization and MT in patients with LV systolic dysfunction. The primary outcome among patients with impaired and preserved LV systolic function after PSM was similar to that from earlier findings before PSM was conducted. A significant interaction between LV function and therapeutic strategy for MACE was observed (interaction p = 0.038). Conclusions: Compared to MT alone for management of patients with CTOs, successful CTO PCI may reduce the risk of MACE in patients with preserved LV systolic function, but not in patients with LV dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Guo, Meng, Lv, Zhong, Wu, Ding, Xu, Zhang and Huang.)

Objective: Left ventricular systolic dysfunction (LVSD) after ST-segment elevation myocardial infarction (STEMI) is associated with poor outcome. Trimethylamine N-oxide (TMAO), a gut metabolite, is linked to cardiovascular diseases but its relationship with LVSD after STEMI remains unclear. The present study therefore aimed to investigate the relationship between TMAO and LVSD at 30 days after a first anterior STEMI. Methods: This was a sub-study from the OCTAMI (Optical Coherence Tomography Examination in Acute Myocardial Infarction) registry. Eligible patients were included in current study if they: (1) presented with a first anterior STEMI; (2) had available baseline TMAO concentration; (3) completed a cardiovascular magnetic resonance examination at 30 days after STEMI. LVSD was defined as left ventricular ejection fraction < 50%. Associations between TMAO and left ventricular ejection fraction, infarct size and left ventricular global strain were examined. Results: In total, 78 patients were included in final analysis. Overall, TMAO was moderately associated with peak cTnI ( r = 0.27, p = 0.01), age ( r = 0.34, p < 0.01), and estimated glomerular filtration rate ( r = -0.30, p < 0.01). At 30-day follow-up, 41 patients were in the LVSD group and 37 in the non-LVSD group. Baseline TMAO levels were not significantly different between the two groups (LVSD vs. non-LVSD: median 1.9 μM, 25-75th percentiles 1.5-3.3 μM vs. median 1.9 μM, 25-75th percentiles 1.5-2.7 μM; p = 0.46). Linear regression analyses showed that TMAO was not associated with left ventricular ejection fraction, infarct size or left ventricular global strain at 30 days (all p > 0.05). Conclusions: TMAO was not significantly correlated with 30-day LVSD in patients with a first anterior STEMI after primary revascularization. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03593928., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Zhou, Yu, Tan, Zhou, Liu, Sheng, Li, Chen, Zhao and Yan.)