Post-Acute Myocardial Infarction Heart Failure Research Articles

S100A8/A9 as a prognostic biomarker with causal effects for post-acute myocardial infarction heart failure

Heart failure is the prevalent complication of acute myocardial infarction. We aim to identify a biomarker for heart failure post-acute myocardial infarction. This observational study includes 1062 and 1043 patients with acute myocardial infarction in the discovery and validation cohorts, respectively. The outcomes are in-hospital and long-term heart failure events. S100A8/A9 is screened out through proteomic analysis, and elevated circulating S100A8/A9 is independently associated with heart failure in discovery and validation cohorts. Furthermore, the predictive value of S100A8/A9 is superior to the traditional biomarkers, and the addition of S100A8/A9 improves the risk estimation using traditional risk factors. We finally report causal effect of S100A8/A9 on heart failure in three independent cohorts using Mendelian randomization approach. Here, we show that S100A8/A9 is a predictor and potentially causal medicator for heart failure post-acute myocardial infarction.

Evidence map of clinical research on Chinese patent medicines for post-acute myocardial infarction heart failure

An evidence map was established to comprehensively sort out the clinical research in the treatment of post-acute myocardial infarction heart failure(P-AMI-HF) with Chinese patent medicines, so as to reveal the distribution of evidence in this field. CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, and EMbase were searched for the randomized controlled trial(RCT), systematic reviews/Meta-analysis, and guidelines/consensus in this field. The evidence was analyzed and displayed in the form of a combination of text, charts, bubble charts, and bar charts, and the quality of RCT, systematic reviews/Meta-analysis, and guidelines/consensus were evaluated by RoB 1.0, AMSTAR2, and AGREE Ⅱ, respectively. A total of 163 RCTs, 4 systematic reviews/Meta-analysis, 1 network Meta-analysis, 2 observational studies, and 5 guidelines/consensus were included. In recent years, the total number of publications in this field has shown an upward trend. There were a variety of Chinese patent medicines in the treatment of P-AMI-HF, among which Shenfu Injection received the most attention. The clinical RCT and systematic reviews/Meta-analysis generally had poor quality, and the RCT mostly had a small size, a single center, and a short cycle. The outcome indicators mainly included cardiac function indicators, myocardial injury markers, total response rate, hemodynamic indicators, and safety indicators, while the characteristic efficacy indicators of TCM received insufficient attention. The development processes of some guidelines/consensus lack standardization, which compromised their authority and rationality. Chinese patent medicines have advantages in the treatment of P-AMI-HF, while there are also problems, which remain to be solved by more high-quality evidence. That is, more large-sample and multi-center clinical studies should be carried out in the future, and the formulation process of relevant systematic reviews/Meta-analysis and guideline/consensus should be standardized and the quality of evidence should be improved. In this way, the effectiveness and safety of Chinese patent medicines in the treatment of P-AMI-HF can be explored.

Network Meta-analysis of efficacy and safety of different traditional Chinese medicine injections in treating post-acute myocardial infarction heart failure

This study aims to systematically review the efficacy and safety of different traditional Chinese medicine injections combined with conventional treatment for patients with post-acute myocardial infarction heart failure. The relevant randomized controlled trial(RCT) was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library with the time interval from inception to May 13, 2023. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Network Meta-analysis was then performed in RevMan 5.3 and Stata 15.1. A total of 68 RCTs involving 11 traditional Chinese medicine injections and 5 995 patients were included. The results were explained based on the surface under the cumulative ranking curve(SUCRA).(1) In terms of reducing major adverse cardiovascular event(MACE), the therapies followed the trend of Xinmailong Injection+conventional treatment(83.8%) > Yiqi Fumai Injection+conventional treatment(57.1%) > Xuebijing Injection+conventional treatment(56.6%) > Shenmai Injection+conventional treatment(53.1%) > Shenfu Injection+conventional treatment(45.3%) > conventional treatment(4.0%).(2) In terms of increasing left ventricular ejection fraction(LVEF), the therapies followed the trend of Yiqi Fumai Injection+conventional treatment(84.0%) > Shenmai Injection+conventional treatment(69.6%) > Shenfu Injection+conventional treatment(62.7%) > Xinmailong Injection+conventional treatment(61.6%) > Shuxuening Injection+conventional treatment(54.8%) > Shenqi Fuzheng Injection+conventional treatment(46.7%) > Shengmai Injection+conventional treatment(45.9%) > Breviscapine Injection+conventional treatment(39.9%) > Danhong Injection+conventional treatment(38.8%) > Huangqi Injection+conventional treatment(38.7%) > conventional treatment(7.3%).(3) In terms of reducing B-type natriuretic peptide(BNP), the therapies followed the trend of Xinmailong Injection+conventional treatment(98.6%) > Shenmai Injection+conventional treatment(57.7%) > Shenfu Injection+conventional treatment(52.5%) > Shengmai Injection+conventional treatment(30.1%) > conventional treatment(11.0%).(4) In terms of reducing cardiac troponin Ⅰ(cTnⅠ), the therapies followed the trend of Shenmai Injection+conventional treatment(92.3%) > Yiqi Fumai Injection+conventional treatment(61.5%) > Shenfu Injection+conventional treatment(51.2%) > Shengmai Injection+conventional treatment(48.1%) > Xinmailong Injection+conventional treatment(26.6%) > conventional treatment(20.3%).(5) In terms of reducing high-sensitivity C-reactive protein(hs-CRP), the therapies followed the trend of Shenmai Injection+conventional treatment(79.9%) > Xinmailong Injection+conventional treatment(68.1%) > Shenfu Injection+conventional treatment(63.1%) > Xuebijing Injection+conventional treatment(56.7%) > Shengmai Injection+conventional treatment(51.1%) > Shenqi Fuzheng Injection+conventional treatment(42.8%) > Huangqi Injection+conventional treatment(34.7%) > conventional treatment(3.5%).(6) A total of 22 RCTs reported the occurrence of adverse reactions, mainly involving the damage of the circulatory system, digestive system, and coagulation function. The current evidence suggested that Xinmailong Injection+conventional treatment may have the best therapeutic effect in reducing MACE and BNP; Yiqi Fumai Injection+conventional treatment may be the best in increasing LVEF; Shenmai Injection+conventional treatment may be the best in reducing cTnI and hs-CRP. The safety needs further quantitative research and analysis. However, more high-quality RCT is required to validate the above conclusions due to limitations in the quality and quantity of the included studies.

Post-Acute Myocardial Infarction Heart Failure Core Genes and Relevant Signaling Pathways.

There is increasing concern about heart failure after myocardial infarction and the current clinical treatment measures for ventricular remodeling. Herein, we present the results of differential gene analysis, pathway enrichment analysis, and characteristic gene screening. Our study identifies 4 core genes ( KLRC2 , SNORD105 , SNORD45B , and RNU5A-1 ) associated with post-acute myocardial infarction (AMI) heart failure. The authors discuss the significance of the identified core genes, their potential implications in immune dysfunction and heart failure, and their relevance to disease regulatory genes. The study concludes by emphasizing the importance of clinical relevance in molecular research and suggests potential therapeutic targets for post-AMI heart failure.

Serum microRNAs and antifibrotic response to eplerenone in acute myocardial infarction complicated by systolic dysfunction

BackgroundAfter myocardial infarction (MI) complicated by heart failure (HF), eplerenone reduced serum concentrations of amino-terminal propeptide of type III collagen (PIIINP) and carboxy-terminal propeptide of type I collagen (PICP). Determining a subgroup who are more prone to decrease their collagen content and to respond better to the antifibrotic effects of mineralocorticoid receptor antagonists (MRA) may be relevant for a personalized treatment approach. Whether circulating microRNAs may identify a subgroup that have experienced a more pronounced antifibrotic effect of eplerenone as measured by a PICP and PIIINP decrease is unclear. MethodsA set of circulating microRNAs linked to cardiac fibrosis (mir-1, mir-21, mir-29a, mir-29b, mir-101, mir-122, mir-133a) were measured at baseline in 198 patients in the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Associations between baseline microRNA levels and changes in both PIIINP and PICP from baseline to month 9 were studied using multivariable analysis of covariance, adjusting for age, sex, history of hypertension and diabetes mellitus, prescription of ACE-inhibitors or angiotensin receptor blockers, baseline PIIINP or PICP, and eplerenone treatment. Furthermore, a treatment-by-microRNA interaction was studied. ResultsFrom the selected microRNAs, only mir-133a was associated with a PICP decrease (ß-6.43, 95%CI-12.71 to −0.15,p = 0.045). None of the microRNAs was associated with a PIIINP change. The microRNAs did not predict an effect of eplerenone on PICP and PIIINP changes. ConclusionAlthough serum mir-133a was associated with PICP change, none of the microRNAs previously linked to cardiac fibrosis predicted an antifibrotic response to eplerenone. Further study is needed to identify other suitable targets for a personalized treatment approach.

Autophagy as a novel insight into mechanism of Danqi pill against post-acute myocardial infarction heart failure

Ethnopharmacological relevanceDanqi Pill, composed of the root of Salvia miltiorrhiza Bunge and the root of Panax notoginseng, is effective in the clinical treatment of myocardial ischemia in coronary heart diseases. A number of studies have shown that autophagy plays an essential role in cardiac function and energy metabolism, and disordered autophagy is associated with the progression of heart failure. However, the effect and mechanism of Danqi pill on autophagy have not been reported yet. Aim of the studyThis study aims to elucidate whether Danqi pill restores autophagy to protect against HF and its potential mechanism. Materials and methodsLeft anterior descending ligation was established to induce an HF rat model, H2O2-stimulated H9C2 cells model was conducted to clarify the effects and potential mechanism of Danqi pill. In vivo, Danqi pill (1.5 g/kg) were orally administered for four weeks and Fenofibrate (10 mg/kg) was selected as a positive group. In vitro, Danqi pill (10–200 μg/mL) was pre-cultured for 24 h and co-cultured with H2O2 stimulation for 4 h. Importantly, transmission electron microscopy and fluorescence GPF-mRFP-LC3 reporter system were combined to monitor autophagy flux. Furtherly, we utilized Compound C, a specific AMPK inhibitor, to validate whether the autophagy was mediated by AMPK-TSC2-mTOR pathway. ResultsDanqi pill significantly improved cardiac function and myocardial injury in HF rats. Intriguingly, Danqi pill potently regulated autophagy mainly by promoting the formation of autophagosomes in vivo. Further results demonstrated that expressions of p-AMPK (P < 0.001) and p-TSC2 (P < 0.001) in cardiac tissue were upregulated by Danqi pill, accompanied with downregulation of p-mTOR (P < 0.01) and p-ULK1(P < 0.01). In parallel with the vivo experiment, in vitro study indicated that Danqi pill dramatically restored autophagy flux and regulated expressions of critical autophagy-related molecules. Finally, utilization of Compound C abrogated the effects of Danqi pill on autophagy flux and the expressions of p-TSC2 (P < 0.05), p-mTOR (P < 0.01) and p-ULK1 (P < 0.05). ConclusionDanqi pill could improve cardiac function and protect against cardiomyocytes injury by restoring autophagy via regulating the AMPK-TSC2-mTOR signaling pathway.

Determinants of anti-fibrotic response to mineralocorticoid receptor antagonist therapy: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) and Early Eplerenone Treatment in Patients with Acute ST-elevation Myocardial Infarction without Heart Failure (REMINDER) trials.

After myocardial infarction complicated by heart failure or diabetes, eplerenone (compared to placebo) significantly decreases amino-terminal propeptide of type III procollagen (PIIINP). Determining the subset of patients who are more prone to have a decrease in PIIINP and those who may respond better to the anti-fibrotic effects of mineralocorticoid receptor antagonists (MRA) therapy may be relevant for a personalized treatment approach. The aim of this study is to identify predictors of a PIIINP decrease and assess potential subgroups of "responders" to eplerenone. Clinical factors and biomarkers were evaluated as predictors of a PIIINP decrease from randomization to month 9 in 323 patients from the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Additionally, the association between PIIINP decrease and the composite of cardiovascular (CV) death or CV hospitalization were also explored. External validation was performed in the REMINDER trial. Female sex, eplerenone, reperfusion therapy, potassium < 4mmol/L, circulating levels of PIIINP ≥ 3.6ng/mL and PINP ≥ 27ng/mL predicted a PIIINP decrease (AUC = 0.75). Randomization PIIINP showed a significant interaction with the treatment allocation: patients with PIIINP ≥ 3.6ng/mL had a better response (decrease in PIIINP) to eplerenone (OR for PIIINP ≥ 3.6 = 2.9, 95% CI 1.46-5.89, p = 0.003) and OR for PIIINP < 3.6 = 1.09, 95% CI 0.55-2.2, p = 0.8; interactionp = 0.026). These findings were internally robust using another statistical approach (LOESS). External validation showed good discrimination (AUC = 0.70). There was a tendency toward a lower rate of CV death/CV hospitalizations in patients with decreased PIIINP (adjusted HR = 0.52, 95% CI 0.26-1.02, p = 0.058). In patients who had a myocardial infarction, clinical factors used in combination and treatment with eplerenone were associated with a PIIINP decrease. Interestingly, higher randomization PIIINP levels might help in identifying patients more prone to have an "anti-fibrotic response" when treated with MRAs. Predictors of an antifibrotic response after MI complicated by HF. Several clinical factors and biomarkers predicted a PIIINP decrease after an MI complicated by HF. There was a significant interaction between baseline PIIINP levels and eplerenone treatment: patients with baseline PIIINP ≥ 3.6 mmol/L treated with eplerenone had the best response (PIIINP decrease).

Understanding the role of echocardiography in remodeling after acute myocardial infarction and development of heart failure with preserved ejection fraction.

Despite the use of reperfusion therapies in the last decades, acute myocardial infarction further remains one of the most frequentcauses of mortality. This is mainly caused by changes in the ventricular architecture leading to ventricular remodeling,followed by progressive development of heart failure. Transthoracic echocardiography is a non-invasive instrument whichcan provide information about the extent of the ischemic process and its consequences but can also predict the outcomes aftermyocardial infarction. Although standard echocardiographic parameters are currently used for risk stratification of these patients,they might not truly reflect left ventricular systolic dysfunction in acute myocardial infarct patients, since the detectionof subtle changes in the myocardial function is beyond their limits. The aim of this review is to underline the use of advancedechocardiographic parameters in identifying patients at risk for developing post-acute myocardial infarction heart failure andsubsequent adverse events. Advanced echocardiographic parameters derived from speckle tracking echocardiography providea detailed assessment on the global and regional left ventricular deformation. Therefore, speckle tracking echocardiographyhas a major role in predicting the prognosis of acute myocardial infarction patients and particularly in the development ofsubsequent heart failure, which might be prevented with early initiation of adequate therapy.

Serum Circulating miR-150 is a Predictor of Post-Acute Myocardial Infarction Heart Failure.

Patients with ischemic heart disease are associated with poor prognosis, and their number has increased globally. Therefore, biomarkers that could predict post-acute myocardial infarction (AMI) heart failure (HF) would be helpful to guide appropriate treatment. Based on the diagnosis on admission and results of echocardiogram performed on admission and 1 year after discharge, the current study recruited 54 patients with post-AMI HF, 59 patients with post-AMI non-HF, and 59 healthy controls. Eight candidate microRNAs (miRs) were screened through real-time quantitative PCR. Serum circulating miR-150 level in the post-AMI HF group was significantly lower than the post-AMI non-HF group (0.4 ± 0.3 versus 0.7 ± 0.3, P < 0.001). Further analysis showed that serum circulating miR-150 level was associated with ejection fraction (EF) 1 year after discharge (P < 0.001). Receiver operating characteristic curve (ROC) analysis found that area under the ROC (AUC) was 0.616 (95%CI = 0.511-0.721, P = 0.034) when BNP was used to predict post-AMI HF, whereas AUC improved to 0.764 (95%CI = 0.674-0.855, P < 0.001) when miR-150 was used. The combination of BNP and miR-150 significantly improved the AUC to 0.807 (95%CI = 0.727-0.886, P < 0.001). Finally, multivariate logistic regression analysis revealed that either LVEF on admission or serum circulating miR-150 level was independently associated with post-AMI HF. Serum circulating miR-150 is a novel biomarker to predict post-AMI HF. Further large sample prospective clinical research is needed to validate its role in the future.

Interleukin-6 and adhesion molecules VCAM-1 and ICAM-1 as biomarkers of post-acute myocardial infarction heart failure.

Acute coronary syndromes are associated with a high prevalence of complications including heart failure (HF). The aim of this study was to investigate the association of novel biomarkers with the occurrence of post-acute myocardial infarction (AMI) HF. A prospective study was conducted with patients admitted to the emergency department with ST-segment elevation myocardial infarction (STEMI). Blood and urine samples were collected for analysis of traditional and novel biomarkers, including interleukin-6, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). We compared the levels of these biomarkers between patients with and without post-STEMI HF. A total of 48 patients were assessed, with a prevalence of males. Fifteen patients (31.2%) had post-STEMI HF. Patients with HF had higher mean values of IL-6, VCAM-1, and ICAM-1 compared to those who did not develop HF (57.06 vs 14.03 pg/mL, P=0.001; 1719.58 vs 1304.34 ng/mL, P=0.001; and 1594.20 vs 1158.74 ng/mL, P<0.001, respectively). The three biomarkers were shown to be good predictors of post-STEMI HF (IL-6: AUC 0.786, P=0.002; VCAM-1: AUC 0.797, P=0.001; and ICAM-1: AUC 0.825, P<0.0001), with the respective cutoff points being calculated based on the best sensitivity and specificity indexes (IL-6: 8.67 pg/mL; VCAM-1: 1501.42 ng/mL; and ICAM-1: 1262.38 ng/mL). Of the three biomarkers, only VCAM-1 and ICAM-1 had a direct linear association between them (r=0.470, P<0.0001). IL-6, VCAM-1, and ICAM-1 were associated with the development of new post-AMI HF symptoms, but only VCAM-1 and ICAM-1 correlated with each other, possibly because they have the same pathophysiological mechanism of action.

Successful contemporary reverse controlled antegrade and retrograde subintimal tracking without contrast medium: a case report

BackgroundContrast-induced acute kidney injury is one of the common adverse events related to percutaneous coronary intervention and a predictor for worse outcome. In the setting of percutaneous coronary intervention for chronic total occlusion, large amounts of contrast medium, more than 200–400 mL, are generally injected. A higher dose of contrast medium causes contrast-induced acute kidney injury more frequently. Therefore, patients who undergo chronic total occlusion-percutaneous coronary intervention are at risk for contrast-induced acute kidney injury.Case presentationWe present the case of a 77-year-old Japanese man with post-acute myocardial infarction angina pectoris, heart failure, and chronic kidney disease who underwent percutaneous coronary intervention for chronic total occlusion in his right coronary artery. In the procedure, the retrograde wire was a visible penetration mark that made contrast medium unnecessary. Contemporary reverse controlled antegrade and retrograde subintimal tracking was successfully achieved and stents were implanted without contrast medium. Contrast medium was injected two times after stent implantation to confirm coronary flow and no perforation. The total amount of contrast medium was only 8 mL for chronic total occlusion-percutaneous coronary intervention.ConclusionChronic total occlusion-percutaneous coronary intervention with contemporary reverse controlled antegrade and retrograde subintimal tracking without contrast medium may be safe and feasible in selected patients.

Combined baseline and one-month changes in big endothelin-1 and brain natriuretic peptide plasma concentrations predict clinical outcomes in patients with left ventricular dysfunction after acute myocardial infarction: Insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) study

ObjectiveIncreased levels of neuro-hormonal biomarkers predict poor prognosis in patients with acute myocardial infarction (AMI) complicated by left ventricular systolic dysfunction (LVSD). The predictive value of repeated (one-month interval) brain natriuretic peptides (BNP) and big-endothelin 1 (BigET-1) measurements were investigated in patients with LVSD after AMI. MethodsIn a sub-study of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS trial), BNP and BigET-1 were measured at baseline and at 1month in 476 patients. ResultsWhen included in the same Cox regression model, baseline BNP (p=0.0003) and BigET-1 (p=0.026) as well as the relative changes (after 1month) from baseline in BNP (p=0.049) and BigET-1 (p=0.045) were predictive of the composite of cardiovascular death or hospitalization for worsening heart failure. Adding baseline and changes in BigET-1 to baseline and changes in BNP led to a significant increase in prognostic reclassification as assessed by integrated discrimination improvement index (5.0%, p=0.01 for the primary endpoint). ConclusionsBoth increased baseline and changes after one month in BigET-1 concentrations were shown to be associated with adverse clinical outcomes, independently from BNP baseline levels and one month changes, in patients after recent AMI complicated with LVSD. This novel result may be of clinical interest since such combined biomarker assessment could improve risk stratification and open new avenues for biomarker-guided targeted therapies. Key messagesIn the present study, we report for the first time in a population of patients with reduced LVEF after AMI and signs or symptoms of congestive HF, that increased baseline values of BNP and BigET-1 as well as a further rise of these markers over the first month after AMI, were independently predictive of future cardiovascular events. This approach may therefore be of clinical interest with the potential of improving risk stratification after AMI with reduced LVEF while further opening new avenues for biomarker-guided targeted therapies.

Percutaneous device closure of ventricular septal defect post-acute myocardial infarction and severe heart failure: possible alternative to surgery in selected cases or just a bridge to surgery?

Percutaneous device closure of ventricular septal defect post-acute myocardial infarction and severe heart failure: possible alternative to surgery in selected cases or just a bridge to surgery?

Prognostic Value of the Thrombolysis in Myocardial Infarction Risk Score in ST-Elevation Myocardial Infarction Patients With Left Ventricular Dysfunction (from the EPHESUS Trial)

The Thrombolysis in Myocardial Infarction (TIMI) risk score remains a robust prediction tool for short-term and midterm outcome in the patients with ST-elevation myocardial infarction (STEMI). However, the validity of this risk score in patients with STEMI with reduced left ventricular ejection fraction (LVEF) remains unclear. A total of 2,854 patients with STEMI with early coronary revascularization participating in the randomized EPHESUS (Epleronone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) trial were analyzed. TIMI risk score was calculated at baseline, and its predictive value was evaluated using C-indexes from Cox models. The increase in reclassification of other variables in addition to TIMI score was assessed using the net reclassification index. TIMI risk score had a poor predictive accuracy for all-cause mortality (C-index values at 30days and 1 year ≤0.67) and recurrent myocardial infarction (MI; C-index values ≤0.60). Among TIMI score items, diabetes/hypertension/angina, heart rate >100 beats/min, and systolic blood pressure <100mm Hg were inconsistently associated with survival, whereas none of the TIMI score items, aside from age, were significantly associated with MI recurrence. Using a constructed predictive model, lower LVEF, lower estimated glomerular filtration rate (eGFR), and previous MI were significantly associated with all-cause mortality. The predictive accuracy of this model, which included LVEF and eGFR, was fair for both 30-day and 1-year all-cause mortality (C-index values ranging from 0.71 to 0.75). In conclusion, TIMI risk score demonstrates poor discrimination in predicting mortality or recurrent MI in patients with STEMI with reduced LVEF. LVEF and eGFR are major factors that should not be ignored by predictive risk scores in this population.

Uncovering a Mineralocorticoid Receptor-Dependent Adipose-Vascular Axis: Implications for Vascular Dysfunction in Obesity?

Obesity, insulin resistance, and type 2 diabetes mellitus (T2DM) are associated with increased levels of aldosterone and activation of cardiovascular mineralocorticoid receptors (MRs) contributing to hypertension and associated cardiovascular disease (CVD) (1). Large randomized controlled trials such as the Randomized Aldactone Evaluation Study (RALES), the Epleronone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), and the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) have demonstrated the CVD-related mortality and morbidity benefits of MR antagonists, further implicating MR signaling as a key mediator of CVD (2). The actions of kidney MR signaling to increase cardiovascular and renal fibrosis and blood pressure is well known; however, recent research suggests that inappropriate activation of extrarenal MR signaling in vascular endothelial cells (ECs), vascular smooth muscle cells (VSMCs), immune cells, and adipocytes promotes insulin resistance, T2DM, and associated CVD (1,3,4). For example, in association with obesity and insulin resistance, perivascular and visceral adipose tissue (PVAT and VAT) is dysfunctional, in part, because of adipose MR activation (3). Furthermore, PVAT and VAT secrete aldosterone, the ligand for MRs in endothelial and smooth muscle cells, and this is increased in obesity (3, …

Prognostic Value of Estimated Plasma Volume in Heart Failure

ObjectivesThe purpose of this study was to assess the prognostic value of the estimation of plasma volume or of its variation beyond clinical examination in a post-hoc analysis of EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study). BackgroundAssessing congestion after discharge is challenging but of paramount importance to optimize patient management and to prevent hospital readmissions. MethodsThe present analysis was performed in a subset of 4,957 patients with available data (within a full dataset of 6,632 patients). The study endpoint was cardiovascular death or hospitalization for heart failure (HF) between months 1 and 3 after post-acute myocardial infarction HF. Estimated plasma volume variation (ΔePVS) between baseline and month 1 was estimated by the Strauss formula, which includes hemoglobin and hematocrit ratios. Other potential predictors, including congestion surrogates, hemodynamic and renal variables, and medical history variables, were tested. An instantaneous estimation of plasma volume at month 1 was defined and also tested. ResultsMultivariate analysis was performed with stepwise logistic regression. ΔePVS was selected in the model (odds ratio: 1.01; p = 0.004). The corresponding prognostic gain measured by integrated discrimination improvement was significant (7.57%; p = 0.01). Nevertheless, instantaneous estimation of plasma volume at month 1 was found to be a better predictor than ΔePVS. ConclusionsIn HF complicating myocardial infarction, congestion as assessed by the Strauss formula and an instantaneous derived measurement of plasma volume provided a predictive value of early cardiovascular events beyond routine clinical assessment. Prospective trials to assess congestion management guided by this simple tool to monitor plasma volume are warranted.

Prognostic value of low QRS voltage in patients with acute coronary syndrome

I have read the article by Tan et al. [ [1] Tan N.S. Goodman S.G. Yan R.T. et al. GRACE ECG substudy and Canadian ACS I Registry investigators. Prognostic significance of low QRS voltage on the admission electrocardiogram in acute coronary syndromes. Int. J. Cardiol. 2015; 190: 34-39 Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar ] with great interest, recently published in your journal. Authors reported that low QRS voltage was found to be an independent predictor of in-hospital mortality, and there was a consistent trend toward higher 6-month cumulative mortality in patients with acute coronary syndrome (ACS) and low QRS voltage. In the present study of Tan et al. there are no data about patient group medications on admission and at discharge. It is well known that optimal medical therapy significantly reduces in-hospital and long term mortality in ACS patients. According to guidelines, it is recommended to use statins, angiotensin-converting enzyme inhibitors (ACEI)/angiotensin-receptor blockers (ARB), oral beta-blockers, long term acetylsalicylic acid, and dual antiplatelet therapy for at least 12 months to reduce the mortality in ACS patients [ 2 Steg P.G. James S.K. Atar D. et al. Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). Eur. Heart J. 2012; 33: 2569-2619 Crossref PubMed Scopus (139) Google Scholar , 3 Hamm C.W. Bassand J.P. Agewall S. et al. ESC Committee for Practice Guidelines. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur. Heart J. 2011; 32: 2999-305 Google Scholar ]. In addition, approximately half of the patients have impaired left ventricle systolic function in the present study of Tan et al. It has been demonstrated that aldosterone antagonists reduce mortality significantly in post-ST elevation myocardial infarction patients with left ventricle systolic dysfunction (ejection fraction <40%) [ [4] Pitt B. Remme W. Zannad F. et al. Eplerenone post-acute myocardial infarction heart failure efficacy and survival study investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N. Engl. J. Med. 2003; 348: 1309-1321 Crossref PubMed Scopus (4028) Google Scholar ]. Therefore, Authors should state the incidence of treatment with statins, dual antiplatelet therapy, beta-blockers, aldosterone antagonists, and ACEI/ARB for both groups and compare the groups regarding their medications. Less medication with optimal medical therapy may be another significant reason for higher mortality rates in patients with low QRS voltage.

22 Retrospective Regional Audit of In-Patient Assessment of Left Ventricular Systolic Function and Guideline-Recommended Prescription of Eplerenone following St-elevation Myocardial Infarction

Introduction The Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) trial demonstrated that eplerenone reduces all-cause mortality and death or hospitalisation for cardiovascular events in patients with symptomatic left ventricular (LV) systolic dysfunction (ejection fraction ≤40%) or diabetes following ST-elevation myocardial infarction (STEMI). Current national and international guidelines recommend initiation of eplerenone in this patient group. We conducted a retrospective audit of assessment of LV systolic function and subsequent prescribing of eplerenone in eligible patients presenting with acute STEMI over a 4-month period. Aims and objectives 1. Establish what proportion of patients presenting with STEMI had in-patient assessment of LV systolic function 2. Identify whether LV systolic function assessment was performed qualitatively or quantitatively 3. Determine what proportion of eligible patients were prescribed eplerenone on hospital discharge Methods Patients from NHS Greater Glasgow and Clyde (GG&C) who underwent primary percutaneous coronary intervention (PPCI) for STEMI were retrospectively (01/08/13–30/11/13) identified using the coronary intervention patient-database at the West of Scotland Regional Heart and Lung Centre (Golden Jubilee National Hospital). Data were collected using electronic patient records and national radiology archive. Qualitative assessment was defined as a subjective description of LV systolic function (normal, mild, moderate or severe impairment). Quantitative assessment was defined as a documented ejection fraction (EF). Patients were considered eligible for eplerenone if they had a qualitative assessment of LV systolic function documented as moderately or severely impaired, or EF ≤ 40% on quantitative assessment, and symptomatic LV systolic dysfunction or diabetes. Results 172 patients were identified. 90% of the total population had in-patient assessment of LV systolic function ([Table 1][1]). All of these patients had qualitative assessment ([Table 1][1]). LV systolic function was quantitatively assessed in 27% (10% modified Simpson’s Biplane method, 11% estimated EF, 5% unspecified) ([Table 1][1]). 8% of patients were considered eligible for eplerenone ([Table 2][2]). Of those eligible, eplerenone was appropriately prescribed on discharge in 21% ([Table 2][2]). View this table: Abstract 22 Table 1 Assessment of LV systolic function View this table: Abstract 22 Table 2 Prescribing of eplerenone in eligible patients Conclusions This audit indicates that national and international guidelines for the assessment and management of LV systolic function post-STEMI are not being adhered to within this region. Identifying those with LV systolic dysfunction post-STEMI is not only of importance for the optimisation of drug therapy, but also for patient selection for implantable defibrillators. The wider implications of LV systolic dysfunction include DVLA-imposed restrictions on driving and critical illness policies. Potential barriers to compliance with guidelines include time-constraints, training and shorter inpatient stay since the adoption of PPCI. These factors may explain the low prescribing rate of eplerenone in eligible patients. [1]: #T1 [2]: #T2

Structural Heart Disease and ST2: Cross-Sectional and Longitudinal Associations With Echocardiography

To further explore the potential role of sST2 in the progression of cardiac disease, this section reviews both the associations with cross-sectional findings and longitudinal changes in cardiac structure and function measured by echocardiography and cardiac magnetic resonance imaging with sST2 levels in a variety of patient populations with or at-risk for cardiovascular disease. In a Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department substudy in patients with acute dyspnea, sST2 levels were found associated with left ventricular ejection fraction (LVEF), and both estimated right ventricular (RV) systolic pressure and RV hypokinesis. In a large cohort of ambulatory patients referred for echocardiograms, sST2 was predominantly associated with RV and not LV structural findings. In contrast, in the Framingham Heart Study, a community cohort of >3,300 participants, sST2 was not associated with either echocardiographic finding, although in the Cardiovascular Health Study, sST2 appeared strongly associated with the presence of diastolic dysfunction. Little evidence exists on the relation of sST2 levels with longitudinal change in cardiac structure and function. A substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) evaluated the association among LV remodeling (defined as an increase in LV end-systolic and -diastolic volumes), sST2, and the benefit of eplerenone and found that sST2 levels were good surrogates of left ventricular remodeling. In the same line, the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study found that more time spent with an sST2 level less than the cutoff of 35ng/L identified patients with a greater probability of a decrease in LV diastolic index over 1 year.

Mineralocorticoid receptor antagonists and therapeutic strategies of cardiovascular damage

In recent years, much attention has focused on the role of aldosterone and mineralocorticoid receptors (MRs) in the pathophysiology of hypertension and cardiovascular disease. Patients with primary aldosteronism, in whom angiotensin II levels are low, have a higher incidence of cardiovascular complications than patients with essential hypertension. The Randomized Aldactone Evaluation Study (RALES) demonstrated that adding a non-specific MR antagonist, spironolactone, to a standard therapy that included angiotensin-converting enzyme (ACE) inhibitors, loop diuretics, and digoxin, significantly reduced morbidity and mortality in patients with moderate to severe heart failure. Similarly, the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) showed that the addition of a selective MR antagonist (ARM), eplerenone, to an optimal medical therapy reduces morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure. These data suggest that aldosterone induces cardiac injury through activation of MRs and support the notion that MR blockade has beneficial effects on aldosterone-dependent cardiac injury, through mechanisms that cannot be simply explained by hemodynamic changes. Although, MRA are highly effective in patients with heart failure, the risk of hyperkalemia should not be overlooked. Serious hyperkalemia events were reported in some MRA clinical trials; however these risks can be mitigated through appropriate patient selection, dose selection, patient education, monitoring, and follow-up.