Anemia in Cardio-Renal Syndrome: clinical impact and pathophysiologic mechanisms

Anemia is a disease that is often associated with heart failure (HF) and renal insufficiency (RI). This unfavorable triad of conditions has been called Cardio-Renal-Anemia Syndrome (CRS). The association of HF, RI, and anemia is poorly reported in multicenter clinical trials, so the pathophysiologic mechanisms and treatment options need to be better defined. When CRS patients develop anemia, a "perfect storm" often occurs: HF and RI cause anemia which will worsen the first two conditions. Anemia appears to be the result of complex interactions between cardiac performance, bone marrow homeostasis, renal dysfunction, and various drug side effects. However, neurohormonal and inflammatory activities play a key role in the beginning and progression of the disease. As a consequence, endogenous erythropoietin activity dysfunction with inadequate production and tissue resistance occurs. Despite the advances of therapy in the neurohormonal activation blockade, mortality and hospitalization in HF still remain unacceptably high, suggesting that specific comorbidity treatments could have a significant positive prognostic impact. Anemia should be recognized as one of the novel targets in HF treatmen

Recent advances in pharmacological treatment of heart failure

Background: Over the last years, several trials offered new evidence on heart failure (HF) treatment. Design and results: For HF with reduced left ventricular ejection fraction, type 2 sodium—glucose cotransporter inhibitors, aside from sacubitril—valsartan, demonstrated extraordinary efficacy in ameliorating patients' prognosis. Some new molecules (eg vericiguat, omecamtiv mecarbil and ferric carboxymaltose) correct iron deficiency and have shown to be capable of furthering reducing the burden of HF hospitalisation. Finally, there is new evidence on the possible therapeutic approaches of HF patients with mid-range or preserved left ventricular ejection fraction. Conclusions: This review aimed to revise the main novelties in the field of HF therapy and focus on how the daily clinical approach to patient treatment is changing

Natriuretic peptides (BNP and NT-proBNP): measurement and relevance in heart failure

For patients presenting with acute dyspnea, an incorrect diagnosis could increase the mortality risk. When used in the evaluation of patients with acute symptoms, brain natriuretic peptide and N-terminal pro-brain natriuretic peptide (BNP and NT-proBNP, respectively) testing is highly sensitive for the diagnosis or exclusion of acute or chronic decompensated heart failure (HF). It has been demonstrated that BNP and proBNP levels can facilitate diagnosis and guide HF therapy. Natriuretic peptide (NP) levels are strictly related with HF severity; they are particularly increased in more advanced New York Heart Association (NYHA) classes and in patients with poor outcome. Therefore elevated NP levels were found to correlate with the severity of left ventricular systolic dysfunction, right ventricular dysfunction and pressures, and left ventricular filling alterations. However, the optimal use of NP determination agrees with patient history, physical examination, and all other diagnostic tools. There are some clinical conditions (ie, obesity, renal insufficiency anemia) for which the NP measurement is not diagnostic. Algorithm building taking into consideration all clinical and echocardiographic parameters, as well as NP measurements, may lead to the earlier identification and better risk stratification of patients with chronic HF, independently from etiology

Natriuretic peptides and NGAL in heart failure: does a link exist?

In recent years there has been growing interest in the development of new diagnostic tools and particularly in laboratory tests for the identification of heart failure (HF) patients. Because of the rise in HF occurrence, it is necessary to use simple and reliable method to recognize those patients at risk before the onset of the clinical symptoms. To date HF diagnosis remains difficult: its symptoms and signs are often non specific as well as being poor sensitive indicators for HF severity. Throughout the last 10 years published literature has highlighted a boom in the use of biomarkers for HF. Both B-type and N-terminal pro-B-type natriuretic peptides have demonstrated specific role in heart failure diagnosis, as well as risk assessment. A single determination of BNP at any time during the development of chronic heart failure (CHF) provides a clinically useful tool to establish the outcome. Renal dysfunction is often associated with heart failure and predicts adverse clinical outcomes. Many studies have recently suggested the clinical use of serum neutrophil gelatinase-associated lipocalin (NGAL) levels in patients admitted to the hospital for acute HF can be used to estimate the risk of early worsening renal function. This could be potentially applied in clinical practice for early identification of renal dysfunction development in patients with HF. NGAL levels appear also to predict renal dysfunction in patients with chronic HF and preserved renal function. For all these reasons, BNP and NGAL are two emerging tools useful for diagnosis and prognosis in HF. The combination of two laboratory biomarkers could potentially identify patients with more elevated risks of both cardiac hemodynamic impairment and kidney dysfunction

Pulmonary congestion assessment in heart failure: traditional and new tools

Congestion related to cardiac pressure and/or volume overload plays a central role in the pathophysiology, presentation, and prognosis of heart failure (HF). Most HF exacerbations are related to a progressive rise in cardiac filling pressures that precipitate pulmonary congestion and symptomatic decompensation. Furthermore, persistent symptoms and signs of congestion at discharge or among outpatients are strong predictors of an adverse outcome. Pulmonary congestion is also one of the most important diagnostic and therapeutic targets in chronic heart failure. The aim of this review is to analyze the importance of clinical, instrumental, and biochemical evaluation of congestion in HF by describing old and new tools. Lung ultrasonography (LUS) is an emerging method to assess pulmonary congestion. Accordingly, we describe the additive prognostic role of chest ultrasound with respect to traditional clinical and X-ray assessment in acute and chronic HF setting

Natriuretic peptides in heart failure: where we are, where we are going.

Tremendous advances have been made in understanding the pathophysiology and treatment of congestive heart failure (CHF). However, diagnosis still remains difficult, even with a comprehensive physical examination. Symptoms such as dyspnea are non-specific and poorly sensitive indicators for early CHF that can be largely undetected. The discovery of natriuretic peptides (BNP) as diagnostic biomarkers has been one of the most critical advances for heart failure diagnosis. Therefore, both B-type and N-terminal pro-B-type have potential role in the diagnosis of heart failure, as well as in prognostic risk assessment. A single determination of BNP at any time during the progression of chronic HF provides a clinically useful tool for risk stratification. The hypothesis that repeated measurements might carry prognostic information beyond a single measure was confirmed in different settings. One of the main interests is given to the values of repeated determinations for monitoring progression of disease, and for the evaluation of the clinical effects of medical therapy. Nevertheless, despite thousands of papers describing their potential utility, current guidelines have not endorsed the highest level of recommendation for their use, in part, because the application in clinical practice is often limited for the absence of well codified cut off. Recently, European guidelines emphasized the role of natriuretic peptides as potential laboratory markers. In the near future, algorithm building will take into consideration clinical and echocardiographic parameters as well as NP measurements, and this may lead to a correct diagnosis and identification of patients at high risk. The purpose of this review is to discuss the clinical approaches and future applications of natriuretic peptides in heart failure and coronary diseas

Molecular dysfunction and phenotypic derangement in diabetic cardiomyopathy

The high incidence and poor prognosis of heart failure (HF) patients affected with diabetes (DM) is in part related to a specific cardiac remodeling currently recognized as diabetic cardiomyopathy (DCM). This cardiac frame occurs regardless of the presence of coronary artery diseases (CAD) and it can account for 15-20% of the total diabetic population. The pathogenesis of DCM remains controversial, and several molecular and cellular alterations including myocardial hypertrophy, interstitial fibrosis, oxidative stress and vascular inflammation, have been postulated. The main cardio-vascular alterations associated with hyperglycemia comprise endothelial dysfunction, adverse effects of circulating free fatty acids (FFA) and increased systemic inflammation. High glucose concentrations lead to a loss of mitochondrial networks, increased reactive oxygen species (ROS), endothelial nitric oxide synthase (eNOS) activation and a reduction in cGMP production related to protein kinase G (PKG) activity. Current mechanisms enhance the collagen deposition with subsequent increased myocardial stiffness. Several concerns regarding the exact role of DCM in HF development such as having an appearance as either dilated or as a concentric phenotype and whether diabetes could be considered a causal factor or a comorbidity in HF, remain to be clarified. In this review, we sought to explain the different DCM subtypes and the underlying pathophysiological mechanisms. Therefore, the traditional and new molecular and signal alterations and their relationship with macroscopic structural abnormalities are described

Co-Management of COVID-19 and heart failure during the COVID-19 pandemic. lessons learned

The COVID pandemic has brought many new challenges worldwide, which has impacted on patients with chronic conditions. There is an increasing evidence base suggesting an interaction between chronic heart failure (HF) and COVID-19, and in turn the prognostic impact of co-existence of the two conditions. Patients with existing HF appear more prone to develop severe complications on contracting COVID-19, but the exact prevalence in patients with mild symptoms of COVID-19 not requiring hospital admission is poorly investigated. In addition, hospitalization rates for acute HF over the pandemic period appear reduced compared to previous periods. Several key issues remain rather unaddressed and, importantly, a specific algorithm focused on diagnostic differentiation between HF and acute respiratory distress syndrome, a severe complication of COVID-19, is still lacking. Furthermore, recent data suggests potential interaction existing between HF treatment and some anti-viral anti-inflammatory drugs prescribed during the infection, raising some doubts about a universal treatment strategy for all patients with COVID-19. With this manuscript, we aim to review the current literature in this field in light of growing understanding of COVID-19 in the setting of the HF population, its associated morbidity and mortality burden, and the impact on healthcare systems. We hope that this may stimulate a discussion to guarantee a better, more tailored delivery of care for patients with HF in the setting of concomitant COVID-19 infection

2D/3D SOIL CONSUMPTION TRACKING IN A MARBLE QUARRY DISTRICT

Abstract. Complex extractive districts, such as the marble quarries in the Apuan Alps (northern Italy), require soil consumption monitoring over the years that could be achieved through high-resolution remotely sensed data. To derive 2D and 3D indicators with appropriate resolution for annual monitoring of high-resolution changes in soil consumption, aerial images, LiDAR acquisitions, satellite data, and Remotely Piloted Aircraft Systems (RPAS) acquisitions were used. In particular, open-access Sentinel-2 multispectral satellite imagery with a spatial resolution of 10 m was used to assess cover changes (2D), and then refined by manual interpretation for 5 years (2016-2021). 3D changes were detected by comparing free aerial LiDAR data from 2009 and 2017, integrated with two stereo models obtained from Pléiades high-resolution satellite images from 2020 and 2022. 3D changes observed over the years by algebraic elevation comparison, performed in QGIS 3.x environment, highlight quarries characterized by intense mining activities (extracted marble blocks, characterized by positive elevation differences) and quarry area management (debris disposal and service infrastructure construction, characterized by negative elevation differences). The combined use of 2D and 3D change indicators can be challenging in order to correctly represent soil consumption over the years. A dual 2D/3D webgis client have been developed for proper representation of 2D/3D spatial indicators of ongoing extraction activities in the Carrara marble basin: high-resolution images have been served as tiled data, while 2D/3D spatial indicators are served as static and/or tiled vector data. Open-Source libraries have used in data processing, serving and representation inside a map interface

Anemia correction by erythropoietin reduces BNP levels, hospitalization rate, and NYHA class in patients with cardio-renal anemia syndrome.

Little is known about the effect of anemia correction with erythropoietin (EPO) on B-type natriuretic peptide (BNP) levels, NYHA class, and hospitalization rate. The aim of the study was to investigate, in patients with cardio-renal anemia syndrome, the effects of EPO on hemochrome and renal function parameters and BNP levels. We also analyzed the effect of EPO therapy on hospitalization rate and NYHA class after 12 months in comparison with a population undergoing to standard therapy. We performed a randomized double-blind controlled study of correction of the anemia with subcutaneous ? (group A n = 13) or ? (group B n = 14) EPO for 12 months in addition to standard therapy with oral iron in 27 subjects. Control group (n = 25 patients) received only oral iron. Significant increase in hemoglobin (Hb), hematocrit (Hct), and red blood cells (RBC) were revealed in EPO groups at 12 months; Hb, group A 12.3 ± 0.6; group B 11.7 ± 0.8; control group 10.6 ± 0.5 g/dl P < 0.0001; Hct group A 34.2 ± 2.3, group B 34 ± 2, control group 32.3 ± 1.8% P < 0.01; RBC, group A 3.9 ± 0.2, group B 3.8 ± 0.2, control group 3.3 ± 0.2, (P < 0.0001). Plasma BNP levels in EPO groups were significantly reduced after 12 months (group A: 335 ± 138 vs. group B: 449 ± 274 pg/ml control group 582 ± 209 pg/ml (P < 0.01). After 12 months of treatment, hospitalization rate and NYHA class were reduced in EPO groups with respect to control group (P < 0.05). Finally, an inverse correlation was observed between BNP and Hb levels in EPO Groups (r = -0.70 P < 0.001). EPO treatment reduces BNP levels and hospitalization rate in patients with cardio-renal anemia syndrome. The correction of anemia by EPO treatment appears able to improve clinical outcome in this subset of patients with heart failur