Abstract
Aims
Sodium–glucose co-transporter 2 inhibition reduces the risk of hospitalization for heart failure and for death in patients with symptomatic heart failure. However, trials investigating ...the effects of this drug class in patients following acute myocardial infarction are lacking.
Methods and results
In this academic, multicentre, double-blind trial, patients (n = 476) with acute myocardial infarction accompanied by a large creatine kinase elevation (>800 IU/L) were randomly assigned to empagliflozin 10 mg or matching placebo once daily within 72 h of percutaneous coronary intervention. The primary outcome was the N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP) change over 26 weeks. Secondary outcomes included changes in echocardiographic parameters. Baseline median (interquartile range) NT-proBNP was 1294 (757–2246) pg/mL. NT-proBNP reduction was significantly greater in the empagliflozin group, compared with placebo, being 15% lower 95% confidence interval (CI) −4.4% to −23.6% after adjusting for baseline NT-proBNP, sex, and diabetes status (P = 0.026). Absolute left-ventricular ejection fraction improvement was significantly greater (1.5%, 95% CI 0.2–2.9%, P = 0.029), mean E/e′ reduction was 6.8% (95% CI 1.3–11.3%, P = 0.015) greater, and left-ventricular end-systolic and end-diastolic volumes were lower by 7.5 mL (95% CI 3.4–11.5 mL, P = 0.0003) and 9.7 mL (95% CI 3.7–15.7 mL, P = 0.0015), respectively, in the empagliflozin group, compared with placebo. Seven patients were hospitalized for heart failure (three in the empagliflozin group). Other predefined serious adverse events were rare and did not differ significantly between groups.
Conclusion
In patients with a recent myocardial infarction, empagliflozin was associated with a significantly greater NT-proBNP reduction over 26 weeks, accompanied by a significant improvement in echocardiographic functional and structural parameters.
ClinicalTrials.gov registration
NCT03087773.
Neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) are associated with the severity of various diseases. The aim of this study was to demonstrate the relationship of NLR and ...MLR with the severity of myocarditis. 202 consecutive patients with myocarditis were retrospectively enrolled in this study. Laboratory parameters and clinical data were extracted from hospital records and discharge letters. Median NLR was 2.48 (IQR 1.55-4.58) and median MLR was 0.42 (IQR 0.39-0.58). NLR and MLR correlated with HF, CRP and leukocyte count, MLR further correlated inversely with LV systolic function (rs = - 0.379, p = 0.030). Both ratios correlated better with length of hospital stay (NLR: rs = 0.435, p = 0.003; MLR: rs = 0.534, p < 0.0001) than CRP, leukocyte count, IL-6 or procalcitonin. AUCs for the prediction of prolonged hospital stay (NLR = 0.75, MLR = 0.80), and optimal cut-offs therefor were calculated. Patients who had in-hospital complications showed a higher NLR, however, this remained statistically insignificant. NLR and MLR correlated with the length of stay, as well as with several clinical and laboratory parameters in patients with myocarditis. Since white blood cell differentials are relatively easy and fast to perform, both ratios could facilitate further risk stratification in affected patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Blood urea nitrogen (BUN) was reported to be associated with mortality in heart failure patients. We aimed to evaluate admission BUN concentration in a heterogeneous critically ill patient collective ...admitted to an intensive care unit (ICU) for prognostic relevance.
A total of 4176 medical patients (67±13 years) admitted to a German ICU between 2004 and 2009 were included. Follow-up of patients was performed retrospectively between May 2013 and November 2013. Association of admission BUN and both intra-hospital and long-term mortality were investigated by Cox regression. An optimal cut-off was calculated by means of the Youden-Index.
Patients with higher admission BUN concentration were older, clinically sicker and had more pronounced laboratory signs of multi-organ failure including kidney failure. Admission BUN was associated with adverse long-term mortality (HR 1.013; 95%CI 1.012-1.014; p<0.001). An optimal cut-off was calculated at 28 mg/dL which was associated with adverse outcome even after correction for APACHE2 (HR 1.89; 95%CI 1.59-2.26; p<0.001), SAPS2 (HR 1.85; 95%CI 1.55-2.21; p<0.001) and several parameters including creatinine in an integrative model (HR 3.34; 95%CI 2.89-3.86; p<0.001). We matched 614 patients with admission BUN >28 mg/dL to case-controls ≤ 28mg/dL corrected for APACHE2 scores: BUN above 28 mg/dL remained associated with adverse outcome in a paired analysis with the difference being 5.85% (95%CI 1.23-10.47%; p = 0.02).
High BUN concentration at admission was robustly associated with adverse outcome in critically ill patients admitted to an ICU, even after correction for co-founders including renal failure. BUN might constitute an independent, easily available and important parameter for risk stratification in the critically ill.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression by binding to target messenger RNAs (mRNAs). miRNAs have been implicated in a variety of cardiovascular and ...neurological diseases, such as myocardial infarction, cardiomyopathies of various geneses, rhythmological diseases, neurodegenerative illnesses and strokes. Numerous studies have focused on the expression of miRNA patterns with respect to atrial fibrillation (AF) or acute ischemic stroke (AIS) However, only a few studies have addressed the expression pattern of miRNAs in patients with AF and AIS in order to provide not only preventive information but also to identify therapeutic potentials. Therefore, the aim of this review is to summarize 18 existing manuscripts that have dealt with this combined topic of AF and associated AIS in detail and to shed light on the most frequently mentioned miRNAs-1, -19, -21, -145 and -146 with regard to their molecular mechanisms and targets on both the heart and the brain. From this, possible diagnostic and therapeutic consequences for the future could be derived.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Circulating biomarkers are currently under scientific discussion as a potential tool for the diagnosis, prediction and risk stratification of cardiovascular and metabolic diseases ...
Although reperfusion therapy has improved outcomes, acute myocardial infarction (AMI) is still associated with both significant mortality and morbidity. Once irreversible myocardial cell death due to ...ischemia and reperfusion sets in, scarring leads to reduction in left ventricular function and subsequent heart failure. Regenerative cardiovascular medicine experienced a boost in the early 2000s when regenerative effects of bone marrow stem cells in a murine model of AMI were described. Translation from an animal model to stem cell application in a clinical setting was rapid and the first large trials in humans suffering from AMI were conducted. However, high initial hopes were early shattered by inconsistent results of randomized clinical trials in patients suffering from AMI treated with stem cells. Hence, we provide an overview of both basic science and clinical trials carried out in regenerative cardiovascular therapies. Possible pitfalls in specific cell processing techniques and trial design are discussed as these factors influence both basic science and clinical outcomes. We address possible solutions. Alternative mechanisms and explanations for effects seen in both basic science and some clinical trials are discussed here, with special emphasis on paracrine mechanisms via growth factors, exosomes, and microRNAs. Based on these findings, we propose an outlook in which stem cell therapy, or therapeutic effects associated with stem cell therapy, such as paracrine mechanisms, might play an important role in the future. Optimizing stem cell processing and a better understanding of paracrine signaling as well as its effect on cardioprotection and remodeling after AMI might improve not only AMI research, but also our patients' outcomes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The lactate/albumin ratio has been reported to be associated with mortality in pediatric patients with sepsis. We aimed to evaluate the lactate/albumin ratio for its prognostic relevance in a larger ...collective of critically ill (adult) patients admitted to an intensive care unit (ICU). A total of 348 medical patients admitted to a German ICU for sepsis between 2004 and 2009 were included. Follow-up of patients was performed retrospectively between May 2013 and November 2013. The association of the lactate/albumin ratio (cut-off 0.15) and both in-hospital and post-discharge mortality was investigated. An optimal cut-off was calculated by means of Youden's index. The lactate/albumin ratio was elevated in non-survivors (
< 0.001). Patients with an increased lactate/albumin ratio were of similar age, but clinically in a poorer condition and had more pronounced laboratory signs of multi-organ failure. An increased lactate/albumin ratio was associated with adverse in-hospital mortality. An optimal cut-off of 0.15 was calculated and was associated with adverse long-term outcome even after correction for APACHE2 and SAPS2. We matched 99 patients with a lactate/albumin ratio >0.15 to case-controls with a lactate/albumin ratio <0.15 corrected for APACHE2 scores: The group with a lactate/albumin ratio >0.15 evidenced adverse in-hospital outcome in a paired analysis with a difference of 27% (95%CI 10-43%;
< 0.01). Regarding long-term mortality, again, patients in the group with a lactate/albumin ratio >0.15 showed adverse outcomes (
< 0.001). An increased lactate/albumin ratio was significantly associated with an adverse outcome in critically ill patients admitted to an ICU, even after correction for confounders. The lactate/albumin ratio might constitute an independent, readily available, and important parameter for risk stratification in the critically ill.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The aim of this study was to investigate the role of serum irisin level in predicting clinical outcome in heart failure (HF) patients with type 2 diabetes mellitus (T2DM).
153 T2DM patients with HF ...aged 41-62 years were prospectively recruited for the study. Serum levels of irisin and NT-proBNP were measured by ELISA. Laboratory tests including HbA1c, fasting glucose, blood creatinine, insulin, lipids and creatinine with estimation of GFR were performed along with echocardiography at baseline. The observation period was 56 weeks.
We identified 76 composite cardiovascular (CV) outcomes, which included CV death and death from all causes, resuscitated cardiac death, non-fatal/fatal acute myocardial infarction or stroke, and HF hospitalization. Therefore, the entire patient cohort was divided into 2 groups with (
= 76) and without (
= 77) composite CV outcomes. We found that the concentrations of NT-proBNP were higher in HF patients with T2DM who had a CV composite outcome than in patients without CV composite outcome (
= 0.001). In contrast, the relationship was exactly reversed for irisin, as HF and T2DM patients with CV composite outcome had significantly lower irisin levels (
= 0.001). Unadjusted multivariate Cox regression analyses showed that LVEF < 40%, LAVI > 39 ml/m
, NT-proBNP > 2,250 pmol/ml, and irisin < 6.50 ng/ml were the strongest predictors of CV outcomes in HF patients with T2DM. After adjustment for LVEF, serum levels of NT-proBNP and irisin remained independent predictors of end points. Furthermore, divergence of Kaplan-Meier curves pointed out that patients with NT-proBNP > 2,250 pmol/ml and irisin < 6.50 ng/ml had worse prognosis than those with any other compartment of the bomarkers' levels.
Adding irisin to NT-proBNP significantly improved discriminative value of the whole model. HF patients with T2DM had significantly worse clinical outcomes when showing the constellation NT-proBNP > 2,250 pmol/ml and irisin < 6.50 ng/ml, respectively, in comparison to patients with opposite trends for both biomarkers.
Adipose tissue dysfunction is a predictor for cardiovascular (CV) events and heart failure (HF) in patient population with obesity, metabolic syndrome, and known type 2 diabetes mellitus. Previous ...preclinical and clinical studies have yielded controversial findings regarding the role of accumulation of adipose tissue various types in CV risk and HF-related clinical outcomes in obese patients. There is evidence for direct impact of infiltration of epicardial adipocytes into the underlying myocardium to induce adverse cardiac remodeling and mediate HF development and atrial fibrillation. Additionally, perivascular adipocytes accumulation is responsible for release of proinflammatory adipocytokines (adiponectin, leptin, resistin), stimulation of oxidative stress, macrophage phenotype switching, and worsening vascular reparation, which all lead to microvascular inflammation, endothelial dysfunction, atherosclerosis acceleration, and finally to increase in CV mortality. However, systemic effects of white and brown adipose tissue can be different, and adipogenesis including browning of adipose tissue and deficiency of anti-inflammatory adipocytokines (visfatin, omentin, zinc-α2-glycoprotein, glypican-4) was frequently associated with adipose triglyceride lipase augmentation, altered glucose homeostasis, resistance to insulin of skeletal muscles, increased cardiomyocyte apoptosis, lowered survival, and weak function of progenitor endothelial cells, which could significantly influence on HF development, as well as end-organ fibrosis and multiple comorbidities. The exact underlying mechanisms for these effects are not fully understood, while they are essential to help develop improved treatment strategies. The aim of the review is to summarize the evidence showing that adipocyte dysfunction may induce the onset of HF and support advance of HF through different biological mechanisms involving inflammation, pericardial, and perivascular adipose tissue accumulation, adverse and electrical cardiac remodeling, and skeletal muscle dysfunction. The unbalancing effects of natriuretic peptides, neprilysin, and components of renin–angiotensin system, as exacerbating cause of altered adipocytokine signaling on myocardium and vasculature, in obesity patients at high risk of HF are disputed. The profile of proinflammatory and anti-inflammatory adipocytokines as promising biomarker for HF risk stratification is discussed in the review.
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