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

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

The role of the kidney in acute and chronic heart failure

Renal dysfunction affects approximately 30 to 50% of heart failure (HF) patients. The unfavourable relationship between heart and kidney dysfunction contributes to worse outcomes through several mechanisms such as inflammation, oxidative stress, impaired hydrosaline homeostasis, and diuretic resistance. Renal dysfunction not only carries important prognostic value both in acute and in chronic HF, but also is a potential precipitating factor after the first diagnosis. Because renal dysfunction encompasses different etiologies, a better understanding of its definition, incidence, and pathophysiology provides additional information. Although old and novel available biomarkers for the detection of renal dysfunction have been recently proposed, there is no general consensus regarding the terminology and definition of renal dysfunction in HF. Due to some specific pathophysiological mechanisms, renal impairment seems to be different on an individual patient level and, recognizing it in acute and chronic settings, could be useful to optimize decongestive treatment. For these reasons, in this review, we aim to describe and evaluate different phenotypes of renal dysfunction in acute and chronic HF and the possible management in these settings. Key messages center dot Chronic kidney dysfunction and worsening renal function are highly prevalent in acute heart failure and chronic heart failure and associated with poor outcomes. center dot This association is modified by the context in which it occurs, i.e. worsening renal function in the context of adequate decongestion in acute heart failure, or worsening renal function after initiation of neurohormonal blockers in chronic heart failure. center dot Future research should be aimed at elucidating the mechanisms involved in these differenct contexts, as well as alternative treatment approaches in the case of true worsening renal function

Structural and Hemodynamic Changes of the Right Ventricle in PH-HFpEF

One of the most important diagnostic challenges in clinical practice is the distinction between pulmonary hypertension (PH) due to primitive pulmonary arterial hypertension (PAH) and PH due to left heart diseases. Both conditions share some common characteristics and pathophysiological pathways, making the two processes similar in several aspects. Their diagnostic differentiation is based on hemodynamic data on right heart catheterization, cardiac structural modifications, and therapeutic response. More specifically, PH secondary to heart failure with preserved ejection fraction (HFpEF) shares features with type 1 PH (PAH), especially when the combined pre- and post-capillary form (CpcPH) takes place in advanced stages of the disease. Right ventricular (RV) dysfunction is a common consequence related to worse prognosis and lower survival. This condition has recently been identified with a new classification based on clinical signs and progression markers. The role and prevalence of PH and RV dysfunction in HFpEF remain poorly identified, with wide variability in the literature reported from the largest clinical trials. Different parenchymal and vascular alterations affect the two diseases. Capillaries and arteriole vasoconstriction, vascular obliteration, and pulmonary blood fluid redistribution from the basal to the apical district are typical manifestations of type 1 PH. Conversely, PH related to HFpEF is primarily due to an increase of venules/capillaries parietal fibrosis, extracellular matrix deposition, and myocyte hypertrophy with a secondary "arteriolarization" of the vessels. Since the development of structural changes and the therapeutic target substantially differ, a better understanding of pathobiological processes underneath PH-HFpEF, and the identification of potential maladaptive RV mechanisms with an appropriate diagnostic tool, become mandatory in order to distinguish and manage these two similar forms of pulmonary hypertension

The role of natriuretic peptides for the diagnosis of left ventricular dysfunction

Natriuretic peptides (NPs) are entered in current guidelines for heart failure (HF) diagnosis and management because of their high specificity and sensibility in screening patients with acute dyspnea. Due to their availability and relatively low cost, they became the first step examinations in HF patients evaluation at hospital admission together with clinical and chest radiography examination. NPs are released following any cardiac haemodynamic stress due to volume or pressure overload and should be considered as a mirror of cardiac condition helping in recognizing patients with poor outcome. Moreover, the exact role of NPs in early HF stages, in isolated diastolic dysfunction, and in general population is questioned. Several promising reports described their potential role; however, the wide cut-off definition, inclusion criteria, and intrinsic measurement biases do not actually consent to their clinical application in these settings. A multimodality strategy including both NPs and imaging studies appears to be the best strategy to define the cardiac dysfunction etiology and its severity as well as to identify patients with higher risk. In this review, we describe the current and potential role of NPs in patients with asymptomatic cardiac insufficiency, evaluating the requirement to obtain a better standardization for imaging as for laboratory criteria

Combined use of lung ultrasound, B-type natriuretic peptide, and echocardiography for outcome prediction in patients with acute HFrEF and HFpEF

Background: Lung ultrasound (LUS) can be used to assess pulmonary congestion by imaging B-lines (‘comets’) for patients with acute heart failure (AHF). Objectives: Investigate relationship of B-lines, plasma concentrations of B-type natriuretic peptide (BNP), and echocardiographic left ventricular (LV) function measured at admission and discharge and their relationship to prognosis for AHF with preserved (HFpEF) or reduced (HFrEF) LV ejection fraction. Methods: Patients with AHF had the above tests done at admission and discharge. The primary outcome was re-hospitalization for heart failure or death at 6 months. Results: Of 162 patients enrolled, 95 had HFrEF and 67 had HFpEF, median age was 80 [77–85] years, and 85 (52%) were women. The number of B-lines at admission (median 31 [27–36]) correlated with respiratory rate (r = 0.75; p < 0.001), BNP (r = 0.43; p < 0.001), clinical congestion score (r = 0.25; p = 0.001), and systolic pulmonary artery pressure (r = 0.42; p < 0.001). At discharge, B-lines were also correlated with BNP (r = 0.69; p < 0.001) and congestion score (r = 0.57; p < 0.001). B-line count at discharge predicted outcome (AUC 0.83 [0.77–0.90]; univariate HR 1.12 [1.09–1.16]; p < 0.001; multivariable HR 1.16 [1.11–1.21]; p < 0.001). Results were similar for HFpEF and HFrEF. Conclusions: LUS appears a useful method to assess severity and monitor the resolution of lung congestion. At hospital admission, B-lines are strongly related to respiratory rate, which may be a key component of the sensation of dyspnea. Measurement of lung congestion at discharge provides prognostic information for patients with either HFpEF or HFrEF

Erratum to: Epidemiology and outcome of the cardio-renal syndrome

n/