Despite considerable advances in the field, heart failure (HF) still poses a significant disease burden among affected individuals since it continues to cause high morbidity and mortality rates. Inflammation is considered to play a key role in disease progression, but the exact underlying pathophysiological mechanisms involved have not yet been fully elucidated. The gut, as a potential source of inflammation, could feasibly explain the state of low-grade inflammation seen in patients with chronic HF. Several derangements in the composition of the microbiota population, coupled with an imbalance between favorable and harmful metabolites and followed by gut barrier disruption and eventually bacterial translocation, could contribute to cardiac dysfunction and aggravate HF. On the other hand, HF-associated congestion and hypoperfusion alters intestinal function, thereby creating a vicious cycle. Based on this evidence, novel pharmaceutical agents have been developed and their potential therapeutic use has been tested in both animal and human subjects. The ultimate goal in these efforts is to reverse the aforementioned intestinal derangements and block the inflammation cascade. This review summarizes the gut-related causative pathways implicated in HF pathophysiology, as well as the associated therapeutic interventions described in the literature.

The point-of-care ultrasound (POCUS) has been effectively used in intensive care units for the management of septic patients. Since it is a time- and cost-effective non-invasive imaging modality, its use in the emergency department (ED) has been advocated for by medical experts. This review summarizes the existing literature regarding the breadth of POCUS as a supplementary tool to the holistic approach of septic patients in the ED setting. A literature search was conducted via PubMed (MEDLINE), Cochrane Library, and Scopus databases, analyzing studies which examined the use of POCUS in the ED for non-traumatic, septic, and/or undifferentiated hypotensive patients, resulting in 26 studies. The first cluster of studies investigates the efficiency of POCUS protocols in the differential diagnosis and its reliability for distributive/septic shock and sepsis management. In the second cluster, POCUS use results in faster sepsis cause identification and improves therapeutic management. The third cluster confirms that POCUS aids in the accurate diagnosis and management, even in rare and complicated cases. The results of the present review support the well-documented utility of POCUS and highlight the importance of POCUS incorporation in the comprehensive management of the septic patient in the ED setting.

Early recognition and timely treatment of sepsis and septic shock is vital. Despite appropriate management, mortality and morbidity rates remain high. In recent years, many of the research efforts have been directed towards finding novel biomarkers that would rapidly identify, classify and risk-stratify the severity of sepsis in order to achieve prompt and targeted treatment of patients with sepsis and septic shock. Among these biomarkers, adrenomedullin (ADM) in the form of the biologically active fragment (bio-ADM) and dipeptidyl peptidase 3 (DPP3) have recently been in the spotlight. The aim of this narrative review is to summarize current evidence on these two novel biomarkers regarding their clinical utility in diagnosis, prognosis, treatment monitoring and therapy guidance of sepsis and septic shock in the emergency department (ED) and in the intensive care unit (ICU) setting. Bio-ADM seems to be a promising biomarker with respect to the overall management of sepsis (diagnosis, severity prediction, prognosis and treatment monitoring and guidance). On the other hand, DPP3 appears to be useful mainly for sepsis prognosis and for predicting sepsis-induced acute kidney injury. Given their potential clinical utility in sepsis management, the use of these two novel biomarkers, in conjunction with established biomarkers and clinical scores, could lead to the application of refined integrated protocols in the ED and the ICU, which could promptly and effectively inform clinical decision-making in patients presenting with sepsis or septic shock.

Background: The aim of the present study is to investigate the prognostic utility of point-of-care (POC)-measured proenkephalin (PENK), a novel biomarker, in terms of predicting in-hospital mortality in patients presenting to the emergency department (ED) with septic shock. Methods: Bedside PENK was measured in consecutive patients presenting to the ED with septic shock according to the Sepsis-3 clinical criteria. The association of PENK with inflammatory and routine biomarkers, and its role as a predictor of in-hospital mortality, was examined. Results: Sixty-one patients with septic shock [53% females, median age 83 years (IQR 71–88)] were evaluated. Median (IQR) values of creatinine, plasma lactate, soluble urokinase plasminogen activator receptor (SuPAR), procalcitonin and PENK were 1.7 (1.0–2.9) mg/dL, 3.6 (2.1–6.8) mmol/L, 13.1 (10.0–21.4) ng/mL, 2.06 (0.84–3.49) ng/mL, and 205 (129–425) pmol/L, respectively. LogPENK significantly correlated with LogLactate (rho = 0.369, p = 0.004), LogCreatinine (rho = 0.537, p < 0.001), LogProcalcitonin (rho = 0.557, p < 0.001), and LogSuPAR (rho = 0.327, p = 0.011). During hospitalization, 39/61 (64%) patients died. In a multivariable logistic regression model, logPENK was an independent predictor of in-hospital mortality (OR 11.9, 95% CI: 1.7–84.6, p = 0.013). Conclusion: POC PENK levels measured upon presentation to the ED strongly correlated with metabolic, renal and inflammatory biomarkers, and may serve as a predictor of in-hospital mortality in patients with septic shock.

Heart failure (HF) is a challenging clinical syndrome with high morbidity and mortality rates. Along the spectrum of cardiovascular diseases, HF constitutes an ever-expanding area of research aiming at combating the associated mortality and improving the prognosis of patients with HF. Although natriuretic peptides have an established role among biomarkers in HF diagnosis and prognosis, several novel biomarkers reflecting the complex pathophysiology of HF are under investigation for their ability to predict adverse clinical outcomes in HF. Proenkephalin 119–159 (PENK_119–159) is a non-functional peptide belonging to the enkephalin family of the endogenous opioid system and is considered a surrogate biomarker of the biologically active enkephalin peptides. PENK_119–159 has demonstrated promising results in predicting short- and long-term mortality, readmission rates, and worsening renal function in patients with HF. Indeed, in the setting of HF, the levels of both active enkephalins and their surrogate PENK_119–159 are elevated and are associated with a dismal prognosis. However, the biological effects of PENK_119–159 remain largely unknown. Thus, it is crucial to gain a deeper insight into both the physiology of the enkephalin peptide family and the enkephalin-mediated cardiovascular regulation. In order to elucidate the complex pathophysiological mechanisms that lead to the upregulation of enkephalins in patients with HF, as well as the potential clinical implications of elevated enkephalins and PENK_119–159 levels in this patient population, the present review will describe the physiology and distribution of the endogenous opioid peptides and their corresponding opioid receptors, with a particular focus on the action of enkephalins. The effects of the enkephalin peptides will be analyzed in both healthy subjects and patients with HF, especially with regard to their role in the regulation of cardiovascular and renal function. The review will also discuss the findings of recent studies that have explored the prognostic value of PENK_119–159 in patients with HF.

The quest for prompt and effective diagnosis of acute myocardial infarction (AMI) has been in the spotlight for decades. Ongoing research focuses on refined biomarker strategies for the early identification and disposition of patients with symptoms suggestive of AMI. Copeptin, a surrogate of the hormone arginine vasopressin, has emerged as a novel biomarker that could potentially aid in the diagnostic approach of patients with chest pain presenting to the emergency department. Observational studies have demonstrated that copeptin is upregulated in patients with AMI, although the exact pathophysiological mechanisms implicated in its release during myocardial ischemia remain unclear. Following these observations, copeptin was proposed as an adjunct to troponin in an effort to augment the diagnostic accuracy of conventional troponin assays. However, after the introduction of high-sensitivity troponin assays, the diagnostic utility of copeptin has been debated. This narrative review aims to elucidate plausible pathophysiological mechanisms involved in copeptin release during myocardial ischemia and to summarize the most recent evidence regarding its diagnostic potential in combination with high-sensitivity troponin assays.