The role of natriuretic peptide testing in guiding chronic heart failure management: Review of available data and recommendations for use

SummaryThe care of patients with heart failure can be challenging, with few objective tools available to assist in therapy decision-making. Natriuretic peptides are powerfully prognostic biomarkers in patients with heart failure and may represent an objective target for therapy. Accordingly, the use of biomarker-guided care with either B-type natriuretic peptide (BNP) or amino-terminal pro-B-type natriuretic peptide (NT-proBNP) has been recently explored. Over the past few years, a number of studies with heterogeneous inclusion criteria, methods and results have been performed. We have reviewed the available literature, summarizing the results of biomarker-guided heart failure trials and deriving recommendations for optimal application of biomarker-guided heart failure care based on the experience gained. In general, positive studies had low BNP or NT-proBNP target concentrations (∼100pg/mL and ∼1000pg/mL, respectively) and achieved lower natriuretic peptide concentrations compared with standard care. Patients in the biomarker-guided arms of the studies typically received more aggressive heart failure care and had no excess adverse outcomes. In the recent ProBNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) study, patients treated with biomarker-guided care also had improved quality of life and significantly better reverse remodeling on echocardiography compared with patients who received standard care. In conclusion, heart failure therapy guided by a goal to reduce natriuretic peptide concentrations below prognostically-meaningful levels results in more aggressive heart failure care, is well tolerated and is associated with superior outcomes

Novel diabetes drugs and the cardiovascular specialist

Recently, treatment with 2 newer classes of type 2 diabetes drugs were found to reduce events in patients with diabetes and cardiovascular (CV) disease, a group common in cardiology clinics. The sodium-glucose cotransporter 2 inhibitor, empagliflozin, markedly and rapidly reduced CV death and heart failure hospitalization, likely with hemodynamic/metabolic-driven mechanisms of action. More recently, the glucagon-like peptide–1 receptor agonists liraglutide and semaglutide also reduced CV death and/or major adverse CV events, but did so more slowly and did not influence heart failure risks, suggesting alternative mechanisms of benefit. We will discuss drug therapy for diabetes relative to CV risk, briefly summarize key findings of CV benefit from recent trials, discuss potential mechanisms for benefits of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide–1 agonists, and suggest how such drugs might be embraced by CV specialists to reduce CV events and mortality in their patients

Effects of canagliflozin on cardiovascular biomarkers in older adults with type 2 diabetes

Background: Sodium glucose co-transporter 2 (SGLT2) inhibitors may reduce cardiovascular and heart failure risk in patients with type 2 diabetes mellitus (T2DM). Objectives: To examine the effects of canagliflozin on cardiovascular biomarkers in older patients with T2DM. Methods: In 666 T2DM patients randomized to receive canagliflozin 100 or 300 mg or placebo, we assessed median percent change in serum N-terminal pro-B type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI) , soluble (s)ST2, and galectin-3 from baseline to 26, 52, and 104 weeks. Results: Both serum NT-proBNP and serum hsTnI levels increased in placebo recipients but remained largely unchanged in those randomized to canagliflozin. Hodges-Lehmann estimates of the difference in median percent change between pooled canagliflozin and placebo were –15.0%, –16.1%, and –26.8% for NT-proBNP, and –8.3%, –11.9%, and –10.0% for hsTnI at weeks 26, 52, and 104, respectively (all P <0.05). Serum sST2 was unchanged with canagliflozin and placebo over 104 weeks. Serum galectin-3 modestly increased from baseline with canagliflozin versus placebo, with significant differences observed at 26 and 52 weeks but not at 104 weeks. These results remained unchanged when only patients with complete samples were assessed. Conclusions: Compared to placebo, treatment with canagliflozin delayed rise in serum NT-proBNP and hsTnI over 2 years in older T2DM patients. These cardiac biomarker data provide support for beneficial cardiovascular effect of SGLT2 inhibitors in T2DM

Natriuretic Peptide Testing in Primary Care

The incidence, as well as the morbidity and mortality associated with heart failure (HF) continue to rise despite advances in diagnostics and therapeutics. A recent advance in the diagnostic and therapeutic approach to HF is the use of natriuretic peptide (NP) testing, including both B-type natriuretic peptide (BNP) and its amino terminal cleavage equivalent (NT-proBNP). NPs may be elevated at an early stage among those with symptoms as well among those without. The optimal approach for applying NP testing in general populations is to select the target population and optimal cut off values carefully. Superior diagnostic performance is observed among those with higher baseline risk (such as hypertensives or diabetics). As well, unlike for acute HF, the cut off value for outpatient testing for BNP is 20-40 pg/mL and for NTproBNP it is 100-150 ng/L. In symptomatic primary care patients, both BNP and NT-proBNP serve as excellent tools for excluding HF based on their excellent negative predictive values and their use may be cost effective. Among those with established HF, it is logical to assume that titration of treatment to achieve lower NPs levels may be advantageous. There are several ongoing trials looking at that prospect

Depression and Cardiac Disease: Epidemiology, Mechanisms, and Diagnosis

In patients with cardiovascular disease (CVD), depression is common, persistent, and associated with worse health-related quality of life, recurrent cardiac events, and mortality. Both physiological and behavioral factors—including endothelial dysfunction, platelet abnormalities, inflammation, autonomic nervous system dysfunction, and reduced engagement in health-promoting activities—may link depression with adverse cardiac outcomes. Because of the potential impact of depression on quality of life and cardiac outcomes, the American Heart Association has recommended routine depression screening of all cardiac patients with the 2- and 9-item Patient Health Questionnaires. However, despite the availability of these easy-to-use screening tools and effective treatments, depression is underrecognized and undertreated in patients with CVD. In this paper, we review the literature on epidemiology, phenomenology, comorbid conditions, and risk factors for depression in cardiac disease. We outline the associations between depression and cardiac outcomes, as well as the mechanisms that may mediate these links. Finally, we discuss the evidence for and against routine depression screening in patients with CVD and make specific recommendations for when and how to assess for depression in this high-risk population

Improving the Diagnosis of Acute Heart Failure Using a Validated Prediction Model

ObjectivesWe sought to derive and validate a prediction model by using N-terminal pro–B-type natriuretic peptide (NT-proBNP) and clinical variables to improve the diagnosis of acute heart failure (AHF).BackgroundThe optimal way of using natriuretic peptides to enhance the diagnosis of AHF remains uncertain.MethodsPhysician estimates of probability of AHF in 500 patients treated in the emergency department from the multicenter IMPROVE CHF (Improved Management of Patients With Congestive Heart Failure) trial recruited between December 2004 and December 2005 were classified into low (0% to 20%), intermediate (21% to 79%), or high (80% to 100%) probability for AHF and then compared with the blinded adjudicated AHF diagnosis. Likelihood ratios were calculated and multiple logistic regression incorporated covariates into an AHF prediction model that was validated internally by the use of bootstrapping and externally by applying the model to another 573 patients from the separate PRIDE (N-Terminal Pro-BNP Investigation of Dyspnea in the Emergency Department) study of the use of NT-proBNP in patients with dyspnea.ResultsLikelihood ratios for AHF with NT-proBNP were 0.11 (95% confidence interval [CI]: 0.06 to 0.19) for cut-point values <300 pg/ml; increasing to 3.43 (95% CI: 2.34 to 5.03) for values 2,700 to 8,099 pg/ml, and 12.80 (95% CI: 5.21 to 31.45) for values ≥8,100 pg/ml. Variables used to predict AHF were age, pre-test probability, and log NT-proBNP. When applied to the external data by use of its adjudicated final diagnosis as the gold standard, the model appropriately reclassified 44% of patients by intermediate clinical probability to either low or high probability of AHF with negligible (<2%) inappropriate redirection.ConclusionsA diagnostic prediction model for AHF that incorporates both clinical assessment and NT-proBNP has been derived and validated and has excellent diagnostic accuracy, especially in cases with indeterminate likelihood for AHF

Prognostic Significance of Elevated Cardiac Troponin-T Levels in Acute Respiratory Distress Syndrome Patients

Background: Elevated levels of biochemical markers of myocardial necrosis have been associated with worsened outcomes in Acute Respiratory Distress Syndrome (ARDS), but there are few prospective data on this relationship. We investigated elevated cardiac troponin T (cTnT) levels and their relationship with outcome in patients with ARDS. Methods A prospective cohort study of patients with ARDS was conducted at a tertiary-care academic medical center. Patients had blood taken within 48 hours of ARDS onset and assayed for cTnT. Patients were followed for the outcomes of 60-day mortality, number of organ failures, and days free of mechanical ventilation. Echocardiographic and electrocardiographic (ECG) data were analyzed for signs of myocardial ischemia, infarction, or other myocardial dysfunction. Results: 177 patients were enrolled, 70 of whom died (40%). 119 patients had detectable cTnT levels (67%). Median cTnT level was 0.03 ng/mL, IQR 0–0.10 ng/mL, and levels were higher among non-survivors (P = .008). Increasing cTnT level was significantly associated with increasing mortality (P = .008). The association between increasing cTnT level and mortality remained significant after adjustment in a multivariate model (HRadj = 1.45, 95% CI 1.17–1.81, P = .001). Elevated cTnT level was also associated with increased number of organ failures (P = .002), decreased number of days free of mechanical ventilation (P = .03), echocardiographic wall motion abnormalities (P = 0.001), and severity of tricuspid regurgitation (P = .04). There was no association between ECG findings of myocardial ischemia or infarction and elevated cTnT. Conclusions: Elevated cTnT levels are common in patients with ARDS, and are associated with worsened clinical outcomes and certain echocardiographic abnormalities. No association was seen between cTnT levels and ECG evidence of coronary ischemia