Renal dysfunction prevalence and clinical impact in heart failure

Alberto Palazzuoli, Susanna Benincasa, Stefanie Grothgar, Pasquale Di Sipio, Giovanni Paganini, Marco Pellegrini, Ranuccio NutiDepartment of Internal Medicine and Metabolic Diseases, Cardiology Section, Le Scotte Hospital, University of Siena, ItalyAbstract: Chronic kidney disease (CKD) is associated with a significant increase in death and cardiovascular mortality. However the exact mechanism by which CKD impairs the cardiovascular outcome is not well established. Some reasons may lie in the association of CKD with several other cardiovascular and noncardiovascular disorders including accelerated systemic atherosclerosis, endothelial dysfunction, increased levels of inflammatory factors, anemic status, bone mineral dysfunction, electrolyte imbalance, and renin–angiotensin–aldosterone system (RAAS) activation. Therefore several risk factors such as hypertension, diabetes, lipid disorders, and older age are common in both conditions. In patients affected with heart failure (HF) a key role is represented by the neurohormonal activation. This condition causes fluid and sodium retention, peripheral vasoconstriction, as well as increased congestion and cardiac workload. Moreover, HF during the decompensated phases is often associated with a worsening renal function that leads to further RAAS activation, microvascular damage, and intrarenal flow redistribution. In order to clarify the interactions between these factors, several questions need to be answered: the universal definition of "worsening renal function," the identification of the best laboratory parameters to investigate renal function in terms of sensitivity and specificity, and a better definition of the comorbidities' role in the determination of the outcome, especially in patients with chronic HF. A clarification of these key points could lead to the individualization of new specific therapeutic targets and to a reduction in mortality and hospitalization in patients with HF and renal impairment.Keywords: heart failure, outcome, renal insufficiency, worsening renal functio

Rationale and study design of intravenous loop diuretic administration in acute heart failure. DIUR-AHF

Aims: Although loop diuretics are the most commonly used drugs in acute heart failure (AHF) treatment, their short-term and long-term effects are relatively unknown. The significance of worsening renal function occurrence during intravenous treatment is not clear enough. This trial aims to clarify all these features and contemplate whether continuous infusion is better than an intermittent strategy in terms of decongestion efficacy, diuretic efficiency, renal function, and long-term prognosis. Methods and results: This is a prospective, multicentre, randomized study that compares continuous infusion to intermittent infusion and a low vs. high diuretic dose of furosemide in patients with a diagnosis of acute heart failure, BNP ≥ 100 pg/mL, and specific chest X-ray signs. Randomization criteria have been established at a 1:1 ratio using a computer-generated scheme of either twice-daily bolus injection or continuous infusion for a time period ranging from 72 to 120 h. The initial dose will be 80 mg/day of intravenous furosemide and, in the case of poor response, will be doubled using an escalation algorithm. A high diuretic dose is defined as a furosemide daily amount >120 mg/day respectively. Conclusions: Continuous and high dose groups could reveal a more intensive diuresis and a greater decongestion with respect to intermittent and low dose groups; high dose and poor loop diuretic efficiency should be related to increased diuretic resistance, renal dysfunction occurrence, and greater congestion status. Poor diuretic response will be associated with less decongestion and an adverse prognosis

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

Acute Coronary Syndromes: From The Laboratory Markers To The Coronary Vessels

A number of “interesting” risk markers have been proposed as providing prognostic informations in acute coronary syndromes (ACS). Elevation in plasma inflammatory and necrosis biomarkers have been related to future cardiovascular events in individuals with or without prior myocardial infarction. Recently BNP and pro-BNP are entered in clinical practice to recognize patients at major risk, providing incremental information respect to the traditional markers. Together with these laboratory indexes, a few of promising laboratory markers once easily available, could become usefull in identification of patients at high risk

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

Dynamics and relaxation in new florinated side-chain polymers: an ESR investigation

Fluorinated azobenzene liquid crystalline polymers appear promising materials as optical data storage substrates, especially in holographic recording, for their ability of suppressing surface relief (1). Their applicative importance also arises from the excellent water repellency (2) and the possibility of modulating wettability by the change in the dipole moment of the cis-trans photochromic species (3). The comprehension of the mechanism by which the internal structure and molecular architecture of these materials affect their microscopic relaxation phenomena will address an ever improved design for technological applications and a fundamental understanding, enlightening the presence of cooperative mechanisms or/and dynamic heterogeneity. A new series of fluorinated homopolymers and random copolymers were investigated. They share the same main chain, and differentiate from a previous series (4, 5) for the substitution of the −(2)43 group with the −3 one in the terminal part of the azobenzene-containing side chain. The study was carried out by electron spin resonance to investigate the dynamics and matrix heterogeneity of the new series of copolymers, also in comparison with the previous non-fluorinated series. The structural relaxation of the polymers was also investigated by rheological measurements. Different molecular architectures result in modulation of the relaxation properties at nanoscale level. Dynamics and matrix heterogeneity is discussed, highlighting how the different molecular architecture affects different dynamic responses and matrix heterogeneity over different length and time scales. Information on cooperativity of the dynamics is also provided. References 1. F. You, M.Y.Paik, M. Häckel, L. Kador, D. Kropp, H.W. Schmidt, and C.K.Ober. Adv. Funct. Mater., 16: 1577, 2006. 2. S.D. Xiong, X.L. Guo, L. Li, S.l. Wu, P.K. Chu, and Z.S. Xu. J. Fluorine Chem., 131: 417, 2010. 3. K.Ichimura, S.K.Oh, and M.Nakagawa. Science, 288 (5471): 1624, 2000. ; S.Abbott, J.Ralston, G.Reynold, and R.Hayes. Langmuir, 15: 8923, 1999; L. M. Siewierski, W. J.Brittain, S.Petrash, and M.D.Foster. Langmuir, 12: 5838, 1996. 4. L. Andreozzi, M. Faetti, M. Giordano, D. Palazzuoli, and G. Galli. Macromolecules, 34: 7325, 2001. 5. L. Andreozzi, G. Galli, M. Giordano, E. Martinelli, and F. Zulli Macromolecules, 48: 6541, 201

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