Biomarkers Beyond the Natriuretic Peptides for Chronic Heart Failure: Galectin-3 and Soluble ST2.

B-type natriuretic peptide (BNP) and NT-proBNP are widely used plasma biomarkers for the diagnosis of acute decompensated heart failure and prognosis for future cardiac disease. The clinical performance of these tests for management of chronic heart failure is somewhat limited by the markers' high biological variation. Biomarkers such as galectin-3 and soluble ST2 that reflect ongoing remodeling via cardiac fibrosis of the heart may provide complementary information to the natriuretic peptides in the management of chronic heart failure with regards to risk stratification for future adverse cardiac events (death, myocardial infarction, and need for heart transplantation). However, implementation of these biomarkers into routine clinical practice requires documentation that these tests will enable therapeutic decisions that can be made to improve clinical outcomes, and the availability of commercial assays. This report will discuss the need for novel heart failure biomarkers, ideal characteristics of assays, and review and compare the clinical performance of assays for galectin-3 and sST2 for chronic heart failure disease management

Acute kidney injury on chronic kidney disease: From congestive heart failure to light chain deposition disease and cast nephropathy in multiple myeloma

Acute on chronic renal failure is a common but notably broad diagnosis. We present a 64-year-old man with a history of diastolic heart failure and chronic kidney disease, admitted for an elevated creatinine. History and physical examination were suggestive of decompensated heart failure; however, the careful interpretation of urinalysis rendered the diagnosis of multiple myeloma. On renal biopsy, the patient was found to have light chain deposition disease with cast nephropathy. Combination lesions in multiple myeloma are rare and require diligent histopathology for detection, including light microscopy, immunofluorescence and electron microscopy. These patients portray different demographics, renal manifestations, oncologic characteristics and outcomes, and hence, further studies isolating these combined lesions are warranted

ST2 and Multimarker Testing in Acute Decompensated Heart Failure

Most data on heart failure biomarkers have been derived from patient cohorts with chronic disease. However, risk prediction in patients admitted with acute decompensated heart failure (ADHF) remains a challenge. ADHF is not a single disease: it presents in various manners, and different causes may underlie ADHF, which may be reflected by different biomarkers. Soluble suppression of tumorigenicity 2 (ST2) has been shown to be a strong independent predictor of short-, mid-, and long-term outcome in ADHF. Furthermore, combining biomarkers may help further improve the prognostic power of ST2. The ProBNP Investigation of Dyspnea in the Emergency Department study showed that elevated plasma levels of ST2 together with elevated levels of 4 other biomarkers have clear incremental values to predict outcome in ADHF. The Multinational Observational Cohort on Acute Heart Failure study is an international collaborative network that recruited 5,306 patients hospitalized for ADHF that demonstrated that ST2 and midregional pro-adrenomedulin had independently strong value to predict 30-day and 1-year outcome in patients with ADHF. The Multinational Observational Cohort on Acute Heart Failure study also showed that C-reactive protein plus ST2 better classified risk in patients with ADHFs than ST2 alone. Combining biomarkers for risk prediction or risk stratification might have clinical and more importantly pathophysiological meaning

A Multi-marker Model for Predicting Decompensated Heart Failure in Patients with Prior Acute Myocardial Infarction

The aim of the study was to assess the prognostic value of determining the plasma concentration of NT-proBNP and ST2 in the patients with decompensated HF and prior acute myocardial infarction and their combination in this category of patients.Materials and methods. There were examined 120 patients with acute myocardial infarction and stage II A-B decompensated chronic HF according to the classification proposed by Vasylenko V. Kh. and Strazhesko M.D., NYHA functional class (FC) III-IV. The patients with Q-QS wave MI (60 individuals) and non Q MI (60 individuals) were divided into 4 groups depending on the treatment methods.Study groups were homogenous by age, gender, disease severity, duration of the post-infarction period, clinical signs of decompensation, which served as a basis for inclusion of the patients in the study.All the patients underwent the six-minute walk test in a quiet 30-50-m long hospital corridor in the morning. N-terminal pro-B-type brain natriuretic peptide (NT-proBNP) and ST-2 were analyzed in all patients.Results. Promising biomarkers of HF decompensation in the post-infarction period were studied. In the patients with prior Q-QS MI and decompensated HF, NT-proBNP level was (950.38±3.15) pmol/l (p<0.05); in the patients with prior MI without signs of decompensated HF, it was (580.15±3.03) pmol/l (p˂0.05); in apparently healthy individuals, the level of NT-proBNP was found to be (111.20±3.47) pmol/l.ST2 level was (14.80±1.61) ng/ml, (36.00±1.43) ng/ml and (49.22±1.40) ng/ml in the patients of Group 1, Group 2 and Group 3, respectively (p˂0.05).Similar changes were found in patients with decompensated HF in postinfarction period after non Q MI. Conclusions. The increase in plasma concentration of sST2 is associated with the activation of both neurohumoral and fibrous pathways and can help in detecting the patients with decompensated HF in the post-infarction period and predicting the risk of its development.Our results confirmed the results of other multiple studies reporting ST2 in combination with NT-proBNP to be valuable tools for prognosing the development of decompensated HF in the patients with prior MI. ST2, alongside with NT-proBNP, is a promising biomarker to be included in the diagnostic panel for detecting acute HF and can provide additional information on risk stratification for such patients during hospitalization and at the time of discharge from the hospital

Interleukin-1 blockade in recently decompensated systolic heart failure: study design of the recently decompensated heart failure anakinra response trial (RED-HART)

Heart Failure (HF) is a clinical syndrome characterized by dyspnea, fatigue, and poor exercise capacity due to impaired cardiac function. The incidence of HF is increasing and represents the leading cause of hospitalization in the United States among patients > 65 years of age. Neurohormonal blockade has proven to reduce morbidity and mortality; however the persistent toll of HF demonstrates the urgent need to continue to develop novel drugs that target other pathophysiological paradigms. The presence of inflammation in cardiovascular disease has been well-established and interleukin-1 (IL-1), the prototypical proinflammatory agent, has been shown in preclinical animal models to induce cardiac dysfunction. The current study will investigate the role of IL-1 as an inflammatory mediator of HF progression and investigate whether IL-1 blockade with anakinra, recombinant human IL-1 receptor antagonist, improves aerobic exercise performance in patients with recently decompensated systolic HF. This study will be composed of 3 treatment arms (20 patients each): 1) anakinra 100mg daily for 12 weeks; 2) anakinra 100mg daily for 2 weeks followed by placebo for 10 weeks; or 3) placebo for 12 weeks. All patients will be followed for at least 24 weeks. The co-primary endpoints will be placebo-corrected interval changes in peak oxygen consumption (VO2) and ventilatory efficiency (VE/VCO2 slope) measured by Cardiopulmonary Exercise Testing (CPX) after 2 weeks of anakinra treatment. Secondary endpoints will include interval changes in 1) CPX variables at 4, 12 and 24 weeks; 2) echocardiographic measures of cardiac dimension/function; 3) quality of life assessments; 4) inflammatory biomarkers; and 5) clinical outcome including days alive outside of the hospital and survival free of re-hospitalization for HF. The RED-HART study will be the first study to address the potential benefits of IL-1 blockade on aerobic exercise performance in patients with recently decompensated HF

Renal function, electrolytes, and congestion monitoring in heart failure.

Congestion, renal function, and electrolyte imbalance (particularly potassium) are common problems in the management of the complex multi-morbid patient with heart failure (HF). Poor control of these fundamental clinical features is associated with adverse outcomes. Close monitoring of serum potassium and renal function is recommended by most current guidelines during the management of an episode of acute decompensated HF, yet the recommendations remain poorly implemented. Physicians are advised to treat a state of euvolaemia after an admission with decompensated HF and residual congestion is a marker of worse outcome, yet control of congestion is poorly assessed and managed in real-world practice. This document reflects the key points discussed by a panel of experts during a Heart Failure Association meeting on physiological monitoring of the complex multi-morbid HF patient, and here, we present to aspects related to renal function, electrolyte, and congestion monitoring

Nitrates for the Management of Acute Heart Failure Syndromes, A Systematic Review

© The Author(s) 2016Intravenous nitrates are widely used in the management of acute heart failure syndrome (AHFS) yet with lack of robust evidence to support their use. We therefore sought to analyze all randomized studies that evaluated the effects of nitrates on clinical outcomes in patients with AHFS. In total, 15 relevant trials comparing nitrates and alternative interventions in 1824 patients were identified. All but 3 were conducted before 1998. No trials demonstrated a beneficial effect on mortality, apart from 1 trial reporting a reduction in mortality, which was related to the time of treatment. Retrospective review suggests that there is a lack of data to draw any firm conclusions concerning the use of nitrates in patients with AHFS. More studies are needed to evaluate the safety and efficacy of these agents in the modern era of guideline-directed use of heart failure therapy.Peer reviewedFinal Accepted Versio

A biomarker guided approach in heart failure

Heart failure is one of the commonest diagnoses presenting to physicians in the community or hospital care. Symptoms are often subjective, with clinicians having to rely on clinical assessment and radiological imaging to manage these patients. Treatment is often symptomatic with no clear therapeutic goals as yet identified. To date, there are no objective measures to diagnose, predict, prognosticate or guide therapy in compensated and decompensated heart failure, which is why a novel biomarker guided management approach is gaining so much momentum in the clinical community. This review encompasses recent data on this new approach and details on the potential clinical benefits of the most widely studied cardiac biomarkers currently available.peer-reviewe

Management of Mechanical Ventilation in Decompensated Heart Failure.

Mechanical ventilation (MV) is a life-saving intervention for respiratory failure, including decompensated congestive heart failure. MV can reduce ventricular preload and afterload, decrease extra-vascular lung water, and decrease the work of breathing in heart failure. The advantages of positive pressure ventilation must be balanced with potential harm from MV: volutrauma, hyperoxia-induced injury, and difficulty assessing readiness for liberation. In this review, we will focus on cardiac, pulmonary, and broader effects of MV on patients with decompensated HF, focusing on practical considerations for management and supporting evidence

‘Hearts and minds’: association, causation and implication of cognitive impairment in heart failure

The clinical syndrome of heart failure is one of the leading causes of hospitalisation and mortality in older adults. An association between cognitive impairment and heart failure is well described but our understanding of the relationship between the two conditions remains limited. In this review we provide a synthesis of available evidence, focussing on epidemiology, the potential pathogenesis, and treatment implications of cognitive decline in heart failure. Most evidence available relates to heart failure with reduced ejection fraction and the syndromes of chronic cognitive decline or dementia. These conditions are only part of a complex heart failure-cognition paradigm. Associations between cognition and heart failure with preserved ejection fraction and between acute delirium and heart failure also seem evident and where data are available we will discuss these syndromes. Many questions remain unanswered regarding heart failure and cognition. Much of the observational evidence on the association is confounded by study design, comorbidity and insensitive cognitive assessment tools. If a causal link exists, there are several potential pathophysiological explanations. Plausible underlying mechanisms relating to cerebral hypoperfusion or occult cerebrovascular disease have been described and it seems likely that these may coexist and exert synergistic effects. Despite the prevalence of the two conditions, when cognitive impairment coexists with heart failure there is no specific guidance on treatment. Institution of evidence-based heart failure therapies that reduce mortality and hospitalisations seems intuitive and there is no signal that these interventions have an adverse effect on cognition. However, cognitive impairment will present a further barrier to the often complex medication self-management that is required in contemporary heart failure treatment