Myths in Heart Failure: Part I – ED Evaluation
- Jul 23rd, 2018
- Brit Long
Author: Brit Long, MD (@long_brit, EM Attending Physician, San Antonio, TX) // Edited by: Alex Koyfman, MD (@EMHighAK)
A 62-year-old male presents with significant dyspnea with exertion and lower extremity edema. He has a prior history of heart disease, hypertension, and hyperlipidemia, but no known diabetes or heart failure. He has not seen a physician in over 5 years. He is hypertensive on exam, but the rest of his vital signs, including respiratory rate and saturation, are normal. You detect bibasilar rales and 2+ pitting edema bilaterally. Seems pretty straightforward…standard heart failure, right? Do you need a BNP? What role does renal function play? What imaging test should you obtain?
Acute heart failure is one of the most causes of hospitalization in the U.S. for those > 65 years, accounting for over 650,000 ED visits annually in the U.S.1-7 Close to 80% of patients with AHF are first evaluated in the ED.5-7 There are many ways patients may present with AHF, including gradual decline with worsening symptoms over several weeks, hypertensive pulmonary edema, or cardiogenic shock.
Though we see HF daily and there are several sets of guidelines available,8-12 there are several myths and misconceptions in HF evaluation and management. Part I will address these myths/misconceptions in evaluation of acute HF. Part II will look at treatment.
Myth #1 – Natriuretic peptide testing should be routinely used to rule out or rule in acute heart failure.
B-type natriuretic peptide (BNP) and NT-proBNP are the typical natriuretic peptides obtained on laboratory testing. Natriuretic peptides are produced in the cardiac musculature due to myocyte stretch and function in volume and sodium homeostasis.8,10,13 Myocyte stretch releases proBNP, a precursor molecule, which is enzymatically cleaved to NT-proBNP and BNP.13-17 Both increase sodium and water excretion, increase peripheral vasodilation, and decrease activity of the renin angiotensin aldosterone system (RAAS).8,10 BNP’s half-life approximates 20 minutes, and NT-proBNP’s half-life is 3-6 times the half-life of BNP.13-17
These molecules are often used in AHF. An American College of Emergency Physicians (ACEP) clinical policy provides level B recommendations that with BNP < 100 pg/mL or NT-proBNP < 300 pg/mL, AHF is unlikely, while for BNP > 500 pg/mL or NT-proBNP > 1,000 pg/mL, AHF is likely.8 The 2017 American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Failure Society of America (HFSA) guideline updates provide a Level IA recommendation that natriuretic peptides are useful to support the diagnosis or exclusion of AHF, similar to the 2013 guidelines.9,10 However, the literature behind their use in the ED is controversial.
Pearl #1 – Natriuretic peptides should only be used in combination with clinical evaluation. Other causes of elevated BNP should be considered.
Close to 1/4 of patients with dyspnea will not have definitive levels of natriuretic peptides that help clinicians.13-20 An early study evaluating BNP in 1586 patients suggested the biomarker was more accurate than history or exam, with a sensitivity of 90% for BNP > 100 pg/mL and specificity 76%.18 However, emergency physicians were correct in diagnosing AHF in 95% of cases if they were sure of the diagnosis! If emergency physicians did not think AHF was the cause of symptoms, they were right in 92% of cases.18 A separate study found that BNP 100 pg/mL had a sensitivity of 90% and specificity 73%, compared to emergency physicians with sensitivity of 49% and specificity 96%.19 Study authors state BNP may have corrected physician diagnosis, but there is no discussion for patients in whom BNP was incorrect. The gold standard was cardiology diagnosis, which was 90% accurate in diagnosis, but cardiologists disagreed on diagnosis 11% of the time.19
The RED-HOT study evaluated BNP use and 90-day mortality and readmission and found BNP demonstrated an area under the curve of 0.67 (poor correlation).20 One meta-analysis suggested a pooled sensitivity of 95% and pooled specificity of 63% if a cutoff of 100 ng/L was utilized, while NT-proBNP cutoff of 300 ng/L demonstrated pooled sensitivity and specificity 99% and 43%, respectively.21 Another meta-analysis found a sensitivity and specificity of 93.5% and 52.9%, respectively, for BNP, and 90.4% and 38.2%, for NT-proBNP, respectively.22 Though the study states BNP outperformed history and exam findings, the studies that were included had significant weakness including use of cardiologist opinion as gold standard for diagnosis, and few of the included studies evaluated emergency physician judgment and evaluation.22 Remember that phrase, garbage in equals garbage out?… Observational data suggest natriuretic peptides have high sensitivities for AHF diagnosis, but poor to moderate specificity. Higher cutoff values increase specificity, but lower sensitivity. If emergency physicians are not certain in diagnosing AHF exacerbation, natriuretic peptides have less accuracy. It is not clear that these biomarkers can outperform clinician judgment.
What about randomized controlled trial (RCT) data? A 2004 study suggests fewer admissions and decreased cost with natriuretic peptide use; no differences in mortality or readmission rates were found. This study did not blind physicians managing patients, and objective outcomes were no different when utilizing BNP.23 Another study, the IMPROVE-CHF study, evaluated NT-proBNP, finding decreased length of stay (0.7 hours) and decreased cost. However, results show no differences in admissions or readmissions, along with a nonsignificant increase in mortality with NT-proBNP.24 When used in isolation, BNP did not improve diagnostic accuracy, but when added to history and exam, a marginal improvement was present. A separate study found decreased hospital length of stay by 2 days, but no change in ED length of stay or admission rate.25 More recent RCTs suggest no difference in clinical outcomes such as mortality, readmission, or hospital stay.26-30
One major issue is that a large number of other etiologies can elevate natriuretic peptide levels including coronary syndromes, valvular heart disease, pericardial disease, atrial fibrillation, cardiac surgery, cardioversion, older age, anemia, renal failure, pulmonary hypertension, critical illness, sepsis, and burns.21-23 Thus, the test is not specific. Body weight/body mass index (BMI) and gender can affect BNP levels as well.31,32 Elevated BMI actually decreases natriuretic levels.
If used in isolation, BNP may outperform other history and examination features in diagnosis of AHF. However, we rarely, if ever, use tests in isolation. These biomarkers do not outperform overall clinical impression and gestalt. Studies evaluating natriuretic peptides suggest they do not change patient-centered outcomes such as mortality, though they may be associated with reduction in cost and length of stay (admission rates are controversial).26-30 The literature evaluating natriuretic peptides is rife with poor blinding and bias, as well as a variety of different cutoff levels. For an even deeper dive on BNP, see this First10EM post.
Myth #2 – Renal function assessment is of low yield in the evaluation of AHF.
We typically order a variety of labs in the evaluation of these patients. Troponin is one important assessment, as an elevation in troponin is associated with worse outcomes in AHF.9-12 Another important test is renal function, which is also associated with AHF outcomes.9-12
Pearl #2 – Renal function assessment provides valuable information for disease prognosis and severity in AHF.
Complex cardiac, renal, and vascular interactions occur in AHF, with renal impairment limiting sodium and fluid excretion and increasing activation of the renin-angiotensin-aldosterone system (RAAS).9-12,33 Data suggest kidney injury is common in patients presenting with AHF, with 15%-20% of patients demonstrating Cr > 2.0 mg/dL,34-39 and approximately 25%-31% of patients with glomerular filtration rate (GFR) < 60 mL/min.39-44 Renal function is an important laboratory measurement in AHF, as worsening renal function is associated with short and long-term mortality, increased length of stay, and increased rate of return visit/hospitalization.44-48 AHF may also result in renal injury or further decrease renal function (potentially causing cardiorenal syndrome).42,44,45 Each 10 mL/min decrease in GFR is associated with a 7% increase in mortality.48,49 One meta-analysis reports that annual mortality rates for AHF approach 26% for patients without renal disease, 41% with patients with any form of renal impairment, and 51% in patients with moderate or severe renal dysfunction.48 Forman et al. reported that patients with worsening renal disease possess a 7.5 times higher relative risk ratio for mortality in-hospital.41
Pearl #3 – Serum Cr is limited in assessing renal dysfunction in patients presenting acutely with AHF, and BUN is an important predictor of mortality in AHF.
Though renal dysfunction is typically assessed using serum Cr, this measurement is influenced by a significant number of factors such as age, muscle mass, and concomitant medications, and Cr is not sensitive for renal dysfunction.44,49-54 Changes in serum Cr are dependent on baseline kidney function.52,53 Marked decreases in GFR may cause small changes in serum Cr in the first 24-48 hours of renal injury.33,44-49,52,53 Serum Cr is not always associated with renal injury, as it functions as an assessment of renal function rather than injury. Relying on this test in early presenters with AHF (< 24-48 hours) is not recommended, as Cr may not significantly elevate.33,46-49,52,53 However, BUN may be elevated. BUN is reabsorbed in the renal tubules, unlike Cr, and BUN levels are related to RAAS activity, sodium reabsorption, nitrogen production, and protein metabolism.47,52-59 BUN is an important predictor of mortality and morbidity in patients with AHF.54,55 Levels>43 mg/dL are associated with poor outcome.9-12,40 BUN or Cr elevation is associated with poor outcome in AHF, though BUN may be more accurate.
Myth #3 – Chest radiograph is the go-to imaging assessment in AHF exacerbation.
Chest X-ray is one of the most common assessments in AHF, especially in the patient with shortness of breath.8-12,22 However, chest X-ray findings are not definitive and vary.22 Kerley B-lines have a sensitivity of 9.2% and specificity 98.8%, interstitial edema sensitivity 31.1% and specificity 95.1%, cephalization sensitivity 44.7% and specificity 94.6%, alveolar edema sensitivity 5.7% and specificity 98.9%, pulmonary edema sensitivity 56.9% and specificity 89.2%, pleural effusion sensitivity 16.3% and specificity 92.8%, and cardiomegaly sensitivity 74.7% and specificity 61.7% for AHF.22 Close to 20% of chest X-rays demonstrate no findings of AHF, but the test does have value in suggesting another cause of symptoms.9-12,22
Pearl #4 – A more valuable means of diagnosis for pulmonary edema associated with AHF is ultrasound.
Yes, it’s time for some ultrasound love. Point of care ultrasound (POCUS) is an important tool in diagnosis and management of many critical conditions, including AHF. POCUS can provide a rapid and reliable diagnosis, while also evaluating for other conditions. US assessment typically evaluates several components, including the lungs, heart, and inferior vena cava (IVC).22,60,61 US alone with the presence of >3 B lines in >2 bilateral thoracic lung zones has a +LR of 7.4, sensitivity approaching over 90%, and specificity 92.7% for pulmonary edema, while the absence of B lines has a -LR of 0.16.22,62-64 The number of B lines also correlates with AHF severity.65,66 Intravascular volume assessment can take into account IVC diameter and collapsibility.22,60 However, specific numbers vary for IVC collapsibility index, including 20%-50%. An IVC that collapses < 33% is associated with sensitivity close to 80% for volume overload, with specificity 81%-87%.66-69 However, keep in mind that IVC assessment is complicated by many other conditions (tricuspid regurgitation, pulmonary hypertension (pulmonary embolism), and right ventricular myocardial infarction).22,67-69 US also provides an evaluation of cardiac function, which can be completed by measuring the inward movement of the interventricular septum and inferior wall of the LV in systole and degree of excursion of the anterior mitral valve leaflet in diastole.22,60,61 Detecting reduction in LV function has a sensitivity of 77-83% and specificity 74-90%.22,66,67 There are several other assessments including E-point septal separation (EPSS) and diastolic filling restrictive pattern with pulsed Doppler analysis (typically a specialist test). An EPSS measurement > 7 mm suggests ejection fraction (EF) < 50%.70-72 This emDocs post has some great information on EPSS. The key to remember is that lung US plays a vital role in assessment for pulmonary edema with B lines, along with global cardiac function.22,62-64
B lines in the presence of pulmonary edema
– A variety of misconceptions are present concerning the ED evaluation and management of AHF.
– BNP should only be used in conjunction with clinical gestalt and cannot be used in isolation on a reliable basis.
– There are many other conditions that can elevate BNP, and obesity can actually decrease BNP.
– Renal function, including Cr and BUN, are important assessments in the patient with AHF exacerbation. Elevation in these tests are associated with poor outcome.
– Though chest x-ray is considered the go-to imaging test, ultrasound is better for evaluating for the presence of pulmonary edema.
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