Roberto Valle

State of the art: using natriuretic peptide levels in clinical practice

Natriuretic peptide (NP) levels (B‐type natriuretic peptide (BNP) and N‐terminal proBNP) are now widely used in clinical practice and cardiovascular research throughout the world and have been incorporated into most national and international cardiovascular guidelines for heart failure. The role of NP levels in state‐of‐the‐art clinical practice is evolving rapidly. This paper reviews and highlights ten key messages to clinicians:

Diagnosis and Management of Fluid Overload in Heart Failure and Cardio-Renal Syndrome: The “5B” Approach

Cardio-Renal syndrome may occur as a result of either primarily renal or cardiac dysfunction. This complex interaction requires a tailored approach to manage the underlying pathophysiology while optimizing the patients symptoms and thus providing the best outcomes. Patients often are admitted to the hospital for signs and symptoms of congestion and fluid overload is the most frequent cause of subsequent re-admission. Fluid management is of paramount importance in the strategy of treatment for heart failure patients. Adequate fluid status should be obtained but a target value should be set according to objective indicators and biomarkers. Once the fluid excess is identified, a careful prescription of fluid removal by diuretics or extracorporeal therapies must be made. While delivering these therapies, adequate monitoring should be performed to prevent unwanted effects such as worsening of renal function or other complications. There is a very narrow window of optimal hydration for heart failure patients. Overhydration can result in myocardial stretching and potential decompensation. Inappropriate dehydration or relative reduction of circulating blood volume may result in distant organ damage caused by inadequate perfusion. We suggest consideration of the 5B approach. This stands for balance of fluids (reflected by body weight), blood pressure, biomarkers, bioimpedance vector analysis, and blood volume. Addressing these parameters ensures that the most important issues affecting symptoms and outcomes are addressed. Furthermore, the patient is receiving the best possible care while avoiding unwanted side effects of the treatment.

The NT-proBNP assay identifies very elderly nursing home residents suffering from pre-clinical heart failure.

Little is known about the prevalence of heart failure among very old people, although hospitalisation rates for chronic heart failure are very high. Recently, brain natriuretic peptides have emerged as important diagnostic and prognostic serum markers for congestive heart failure.

Role of Bioimpedance Vectorial Analysis in Cardio-Renal Syndromes

The cardio-renal syndromes (CRS) are the result of complex bidirectional organ cross-talk between the heart and kidney, with tremendous overlap of diseases such as coronary heart disease, heart failure (HF), and renal dysfunction in the same patient. Volume overload plays an important role in the pathophysiology of CRS. The appropriate treatment of overhydration, particularly in HF and in chronic kidney disease, has been associated with improved outcomes and blood pressure control. Clinical examination alone is often insufficient for accurate assessment of volume status because significant volume overload can exist even in the absence of peripheral or pulmonary edema on physical examination or radiography. Bioelectrical impedance techniques increasingly are being used in the management of patients with HF and those on chronic dialysis. These methods provide more objective estimates of volume status in such patients. Used in conjunction with standard clinical assessment and biomarkers such as the natriuretic peptides, bioimpedance analysis may be useful in guiding pharmacologic and ultrafiltration therapies and subsequently restoring such patients to a euvolemic or optivolemic state. In this article, we review the use of these techniques in CRS.

Metabolic and toxicological considerations for diuretic therapy in patients with acute heart failure

Introduction: Diuretics are widely recommended in patients with acute heart failure (AHF). However, loop diuretics predispose patients to electrolyte imbalance and hypovolemia, which in turn leads to neurohormonal activation and worsening renal function (WRF). Unfortunately, despite their widespread use, limited data from randomized clinical trials are available to guide clinicians with the appropriate management of this diuretic therapy. Areas covered: This review focuses on the current management of diuretic therapy and discusses data supporting the efficacy and safety of loop diuretics in patients with AHF. The authors consider the challenges in performing clinical trials of diuretics in AHF, and describe ongoing clinical trials designed to rigorously evaluate optimal diuretic use in this syndrome. The authors review the current evidence for diuretics and suggest hypothetical bases for their efficacy relying on the complex relationship among diuretics, neurohormonal activation, renal function, fluid and sodium management, and heart failure syndrome. Expert opinion: Data from several large registries that evaluated diuretic therapy in hospitalized patients with AHF suggest that its efficacy is far from being universal. Further studies are warranted to determine whether high-dose diuretics are responsible for WRF and a higher rate of coexisting renal disease are instead markers of more severe heart failure. The authors believe that monitoring congestion during diuretic therapy in AHF would refine the current approach to AHF treatment. This would allow clinicians to identify high-risk patients and possibly reduce the incidence of complications secondary to fluid management strategies.

Management and monitoring of haemodynamic complications in acute heart failure

The pathophysiology of acute heart failure syndromes (AHFS), defined as a change or worsening in heart failure symptoms and signs, is complex. The variety of adverse neurohormonal adaptations includes increased levels of plasma renin, aldosterone and angiotensin II, all responsible for cardio-renal dysfunction. In fact, such alterations result in an array of clinical changes that include abnormal haemodynamics, altered ventricular filling pressures, pathological neurohormonal responses, leading to fluid overload, congestion and ultimately heart failure symptoms. Clinical pictures can be various: in spite of a usual improvement in dyspnoea, little weight change and significant morbidity are generally observed during hospitalization. Short-term outcomes are characterized by a high 60-day re-hospitalization and high mortality rates; apparently, both can be predicted from pre-discharge characteristics. The most frequently used treatments for AHF care include diuretics, inotropic agents, and vasodilator/vasoactive agents; however, the final therapeutic strategy is often individualized. Diuretics are currently the most used agents, but resistance to diuretic therapy is common. In addition, several studies have demonstrated that aggressive diuresis can contribute to reduced renal function, and high doses of diuretics have been associated with increased morbidity and mortality. Many patients with AHFS also suffer from acute or from chronic renal dysfunction (cardio-renal syndromes type 1 and 2, respectively), which further complicate the outcomes and treatment strategies. A personalized patient evaluation of the combined heart and kidney functions is advised to implement the best possible multidisciplinary diagnostic and therapeutic approach.

Rationale and study design of intravenous loop diuretic administration in acute heart failure: DIUR‐AHF

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.

ANMCO/ELAS/SIBioC Consensus Document: biomarkers in heart failure

Abstract Biomarkers have dramatically impacted the way heart failure (HF) patients are evaluated and managed. A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological or pathogenic processes, or pharmacological responses to a therapeutic intervention. Natriuretic peptides [B-type natriuretic peptide (BNP) and N-terminal proBNP] are the gold standard biomarkers in determining the diagnosis and prognosis of HF, and a natriuretic peptide-guided HF management looks promising. In the last few years, an array of additional biomarkers has emerged, each reflecting different pathophysiological processes in the development and progression of HF: myocardial insult, inflammation, fibrosis, and remodelling, but their role in the clinical care of the patient is still partially defined and more studies are needed before to be well validated. Moreover, several new biomarkers have the potential to identify patients with early renal dysfunction and appear to have promise to help the management cardio-renal syndrome. With different biomarkers reflecting HF presence, the various pathways involved in its progression, as well as identifying unique treatment options for HF management, a closer cardiologist-laboratory link, with a multi-biomarker approach to the HF patient, is not far ahead, allowing the unique opportunity for specifically tailoring care to the individual pathological phenotype.

Documento di consenso ANMCO/ELAS/SIBioC: Raccomandazioni sull'impiego dei biomarcatori cardiaci nello scompenso cardiaco

Biomarkers have dramatically impacted the way heart failure (HF) patients are evaluated and managed. A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological or pathogenic processes, or pharmacological responses to a therapeutic intervention. Natriuretic peptides (B-type natriuretic peptide [BNP] and N-terminal proBNP) are the gold standard biomarkers in determining the diagnosis and prognosis of HF, and a natriuretic peptide-guided HF management looks promising. In the last few years, an array of additional biomarkers has emerged, each reflecting different pathophysiological processes in the development and progression of HF: myocardial insult, inflammation, fibrosis and remodeling, but their role in the clinical care of the patient is still partially defined and more studies are needed before to be well validated. Moreover, several new biomarkers have the potential to identify patients with early renal dysfunction and appear to have promise to help the management cardio-renal syndrome.With different biomarkers reflecting HF presence, the various pathways involved in its progression, as well as identifying unique treatment options for HF management, a closer cardiologist-laboratory link, with a multi-biomarker approach to the HF patient, is not far ahead, allowing the unique opportunity for specifically tailoring care to the individual pathological phenotype.