Diagnosis of Acute Heart Failure in the Emergency Department: An Evidence-Based Review

Heart failure is a common presentation to the emergency department (ED), which can be confused with other clinical conditions. This review provides an evidence-based summary of the current ED evaluation of heart failure. Acute heart failure is the gradual or rapid decompensation of heart failure, resulting from either fluid overload or maldistribution. Typical symptoms can include dyspnea, orthopnea, or systemic edema. The physical examination may reveal pulmonary rales, an S3 heart sound, or extremity edema. However, physical examination findings are often not sensitive or specific. ED assessments may include electrocardiogram, complete blood count, basic metabolic profile, liver function tests, troponin, brain natriuretic peptide, and a chest radiograph. While often used, natriuretic peptides do not significantly change ED treatment, mortality, or readmission rates, although they may decrease hospital length of stay and total cost. Chest radiograph findings are not definitive, and several other conditions may mimic radiograph findings. A more reliable modality is point-of-care ultrasound, which can facilitate the diagnosis by assessing for B-lines, cardiac function, and inferior vena cava size. These modalities, combined with clinical assessment and gestalt, are recommended.


INTRODUCTION
2][3][4] The condition covers a large spectrum of disease, ranging from mild exacerbations with gradual increases in edema to cardiogenic shock.[8][9][10][11] Currently, the emergency department (ED) initiates the evaluation and treatment of over 80% of patients with AHF in the U.S. [12][13][14][15][16][17] As the population ages, increasing numbers of patients with HF will present to the ED for evaluation and management.However, making the correct diagnosis can be challenging due to the broad differential diagnosis associated with presenting symptoms and variations in patient presentations.
6][27][28] Patients with HF average at least two hospital admissions per year. 25,29,30][22][23] De novo HF is marked by no previous history of HF combined with symptom appearance after an acute event. 3,4,19,23Mortality in patients with HF can be severe, with up to half of all patients dying within five years of disease diagnosis. 20,21,254][25][26][27] AHF expenditures approach $39 billion per year, which is expected to almost double by 2030. 31,32

METHODS
We searched PubMed and Google Scholar for articles using the keywords "heart failure" and "emergency."We included retrospective studies, prospective studies, systematic reviews and meta-analyses, clinical guidelines, and narrative Volume 20, no.6: November 2019 Diagnosis of Acute Heart Failure in the ED: An Evidence-Based Review Long et al.
reviews focusing on diagnosis of HF including history and physical examination, biomarkers, electrocardiogram (ECG), and imaging.The literature search was restricted to studies published in English.Emergency physicians with experience in critical appraisal of the literature reviewed all of the articles and decided which studies to include for the review by consensus, with a focus on emergency medicine-relevant articles.A total of 124 articles were selected for inclusion in this review.

Anatomy and Pathophysiology
Normal cardiac physiology is dependent on appropriately functioning ventricular contraction, ventricular wall structural integrity, and valvular competence. 28,33,344][35][36] SV is dependent upon the preload (defined as the amount of myocardial muscle fiber stretch at the end of ventricular filling), afterload (defined as the amount of vascular resistance the ventricle must overcome), and contractility (defined as the strength of the myocardial contraction).In patients with HF, left ventricular (LV) dysfunction can be due to impaired LV contraction and ejection (systolic dysfunction), impaired relaxation and filling (diastolic dysfunction), or a combination of both. 28,33n alternate way of defining this would be by the effect on ejection fraction (EF).HF with preserved EF refers to patients with an EF > 50%, while HF with reduced EF refers to patients with an EF < 40%.Borderline preserved EF is defined by HF with an EF of 41-50%. 3,4,17,18,29The most common form is HF with reduced EF, which is primarily related to a decrease in the functional myocardium (typically associated with ischemic disease or a prior myocardial infarction). 3,4,34Additional causes include excessive pressure overload from hypertension, valvular incompetence, and cardiotoxic medications.HF with preserved EF occurs due to impaired ventricle relaxation and filling, which accounts for 30-45% of all HF cases. 22,23,33,37,38is form of HF results in increased end-systolic and diastolic volumes and pressures and is most commonly associated with chronic hypertension, coronary artery disease, diabetes mellitus, cardiomyopathy, and valvular disease.][35][36] Right ventricular failure most commonly results from LV failure.As the right side of the heart fails, increased pressure in the vena caval system elevates pressure in the venous system of the gastrointestinal tract, liver, and extremities, resulting in edema, jugular venous distension, hepatomegaly, bloating, abdominal pain, and nausea. 25,28,33,345][36][37][38] The associated decrease in afterload reduces arterial blood pressure and also activates neurohormones, which increase salt and water retention.][38] In AHF, peripheral vascular flow and end-organ perfusion decrease, causing the body to compensate by neurohormonal activation (ie, the renin-angiotensin system), ventricular remodeling, and release of natriuretic peptides. 25,28,34,35These mechanisms are chronically activated in HF, but worsen during acute exacerbations, resulting in hemodynamic abnormalities leading to further deterioration.[35]

Heart Failure Classification
7,18,34 Other means of classification depend on the presence of cardiomyopathy or acute coronary syndrome (ACS).][41][42][43][44][45] Unfortunately, these classification systems are not as useful for acute exacerbation of HF, thereby limiting their applicability in the ED setting.In the ED, classification is based upon the patient's hemodynamic status, perfusion, and blood pressure. 3,4,30,42This differentiation can guide therapy and provides important prognostic information.7][18][19][20][21][22] The hypertensive form (associated with a systolic blood pressure > 140 millimeters of mercury (mmHg) is commonly associated with pulmonary edema, which may occur rapidly (ie, flash pulmonary edema). 46,4718][19][20][21][22]30 Hypotensive AHF is associated with end-organ hypoperfusion, while systemic and pulmonary edema is minimal.ACS can occur simultaneously with or exacerbate HF and requires emergent coronary angiography. 48,49Right-sided HF is associated with right ventricular dysfunction, leading to systemic venous congestion without pulmonary edema if the LV is not involved. 3,4,30

History and Physical Examination
Due to the complex pathophysiology involved in HF and multiple phenotypes (eg, low-vs high-output, preserved vs reduced EF, left-sided vs right-sided), the history and physical examination may vary.Patients with HF are heterogeneous in terms of the cardiac structure and function, the etiology of their HF, the precipitant of the AHF exacerbation, comorbidities, and current medications.4][55][56] While no single historical factor or examination finding can significantly reduce the likelihood of HF in isolation, initial clinical gestalt has been shown to have a sensitivity of 61% and specificity of 86% for the diagnosis. 57,58][60][61] In particular, advanced age, renal disease, and lower blood pressure are associated with increased mortality in AHF. 60,61recipitating factors for AHF exacerbation can include cardiac and non-cardiac causes. 63,64Cardiac causes include uncontrolled hypertension, dietary or medication noncompliance, aortic dissection, dysrhythmias, and cardiac ischemia. 30,59,63,64Noncardiac causes include pulmonary disease, endocrine disease, infection, worsening renal function, anemia, and medication side effects. 3,4,30,59Patients who are noncompliant with their diet and medications have been found to have a lower EF, higher brain-type natriuretic peptide (BNP) levels, and greater congestion when compared with their counterparts. 30,63,64ysrhythmias are another frequent precipitating cause.Among those, atrial fibrillation is the most common. 17,18,21,298][59] The most common manifestation is dyspnea or edema from elevated LV filling pressures. 4,57-598][59] Additionally, an S3 heart sound can be difficult to detect in the ED setting, and inter-rater reliability can be poor. 3,4,598][59] Lower extremity edema has a sensitivity of 50% and specificity 78%. 57-59A meta-analysis evaluating various signs and symptoms in patients with dyspnea found that no single sign or symptom was sufficiently able to rule out AHF, chronic obstructive pulmonary disease, asthma, or pulmonary embolism. 65However, elevated jugular venous pressure, third heart sound, and lung crepitations were strongly suggestive of a diagnosis of AHF. 65

Laboratory Testing
Laboratory assessment in the patient with suspected AHF can provide important diagnostic and prognostic information. 3,4,30,58,59Testing should include a complete blood count, basic metabolic panel with renal function testing, liver function testing, troponin, and a BNP level. 30,48-50-47,55,56bnormalities in liver function are found in approximately 75% of patients with AHF and are associated with more severe disease. 30,69If the right ventricle is involved, bilirubin and alkaline phosphatase levels may be elevated, while leftsided disease is more commonly associated with elevated transaminase levels. 30,6917][18]70 Decreased glomerular filtration rate (GFR) is associated with increased length of in-hospital stay, short-term mortality, and long-term mortality. 17 every 10 mL/minute decrease in GFR is associated with an increase in mortality of 7%. 71,72roponin testing can assist in prognostication and in the detection of underlying ischemia as a potential inciting event for AHF.Elevated troponin levels are associated with higher re-hospitalization rates and 90-day mortality. 17,18,48,49roponin elevation is common in AHF, as one study found elevated troponin levels in 98% of patients with diagnosed AHF, with 81% of the levels above the 99 th percentile. 73Other studies have suggested that this may be closer to 30-50%. 3,4,30][50] Natriuretic peptides (ie, BNP and NT-proBNP) may be a valuable adjunct when the provider is unclear of the diagnosis. 57-59,74-77BNP is produced by cardiac myocytes when exposed to significant myocardial stretch.Use of BNP and NT-proBNP may be sensitive, but not specific for the diagnosis of AHF.Levels less than 100 picograms (pg) per milliliter (mL) for BNP have demonstrated a sensitivity and specificity of 93.5% and 52.9%, respectively, with negative likelihood ratio (LR-) of 0.2. 57-59Using a 300 pg/mL cut-off for NT-proBNP demonstrates a LR-of 0.09. 59However, elevated levels only moderately increase the likelihood of AHF, as specificity improves to 72.9% with a value of 1550 pg/mL for NT-proBNP. 59,74-795,80,81 Other conditions associated with elevations in natriuretic peptide levels include pulmonary embolism, pulmonary hypertension, valvular heart disease, and acute respiratory distress syndrome.BNP levels of 100-400 pg/mL and NT-proBNP levels of 300-900 pg/mL are non-specific and may require further testing.[74][75][76][77][82][83][84][85][86][87] Although these biomarkers may assist in differentiation of other conditions, studies have not demonstrated improved patient-centered outcomes with use of natriuretic peptides .0][91][92] Data from randomized, controlled trials found that knowledge of the BNP levels did not significantly change the ED treatment, mortality, or readmission rates; however, it may decrease hospital length of stay and total cost.76,[93][94][95][96][97][98][99]

Electrocardiogram
An ECG should be rapidly obtained to evaluate for the etiology or precipitating factors (eg, ACS, atrial fibrillation with rapid ventricular response, ventricular dysrhythmia).

Imaging
Imaging is an important component in the patient with suspected heart failure.The most common modality used is the chest radiograph (CXR).Several findings suggest the diagnosis of heart failure on CXR, including cardiomegaly, central vascular congestion, and interstitial edema (Table 4). 17,18,41,102][104][105] Bedside ultrasound can be valuable for diagnosing AHF, with high specificity and positive likelihood ratios (Table 5).Ultrasound can be used to evaluate for B-lines, pleural effusions, inferior vena cava size and respiro-phasic variability, and cardiac contractility. 59,106-108B-lines are vertical artifacts that result from sound wave reverberation through fluid-filled pulmonary interstitium.7][108][109][110][111][112][113] The number of lung zones examined varies in the literature, with eight thoracic lung zones used in the initial lung ultrasound protocols, while newer studies have used four or six lung zones.B-lines demonstrate high sensitivity and specificity for interstitial edema, 59,107,108 while the identification of pleural effusions is not as helpful. 59ssessment of EF on ultrasound may be assessed with visual assessment or quantitative measurements.Qualitative visual estimation is made by assessing the inward movement of the interventricular septum and inferior wall of the LV during systole. 59,106-113E-point septal separation (EPSS) is a quantitative measurement assessing the distance between the anterior mitral valve leaflet and ventricular septum.][113][114] Ultrasound can also estimate intravascular volume through the measurement of inferior vena cava diameter and percentage change during the respiratory cycle.6][117] One study found that by using a combination of lung, cardiac, and inferior vena cava ultrasound, the authors were able to improve diagnostic accuracy by 20%. 118Others have suggested that combining CXR with ultrasound may increase the sensitivity and specificity for diagnosing AHF. 103

Disposition
Due to the heterogenous nature of heart failure, disposition may be challenging.3][14] Patients with hemodynamic instability or critical illness should be admitted to an intensive care unit, and patients with newly diagnosed HF may benefit from admission for further evaluation and management. 17,18,21,119Other patients who may require admission include those with poor response to medical treatment or inability to obtain follow-up, significant electrolyte abnormalities, elevated blood urea nitrogen or creatinine, or ischemia on ECG or biomarker testing. 120[122][123][124]

CONCLUSION
Heart failure is a common presentation to the ED, which can be confused with other clinical conditions.Acute heart failure refers to the gradual or rapid decompensation of heart failure, resulting from either fluid overload or maldistribution.Typical symptoms can include dyspnea, orthopnea, or edema.The physical examination may reveal pulmonary rales, an S3 heart sound, or extremity edema.Laboratory studies should include an electrocardiogram, complete blood count, basic metabolic profile, coagulation studies, troponin, brain natriuretic peptide, and a chest radiograph.Point-of-care ultrasound can facilitate the diagnosis by assessing for B-lines, cardiac function, and inferior vena cava size.Understanding the diagnostic approach can improve the diagnostic accuracy and allow for more rapid initiation of the correct intervention.

ACKNOWLEDGEMENTS
MG, BL, and AK conceived the idea for this manuscript and contributed substantially to the writing and editing of the review.This manuscript did not use any grants or funding, and it has not been presented in abstract form.This review does not reflect the views or opinions of the U.S. government, Department of Defense, U.S. Army, U.S. Air Force, or SAUSHEC EM Residency Program.
,18,70-72  In patients with AHF, Diagnosis of Acute Heart Failure in the ED: An Evidence-Based ReviewLong et al.

Table 4 .
Chest radiograph findings in acute heart failure. 59Diagnosis of Acute Heart Failure in the ED: An Evidence-Based Review Long et al.

Table 5 .
Bed107e ultrasound findings in acute heart failure.59,107AddressforCorrespondence:BritLong, MD, Brooke Army Medical Center, Department of Emergency Medicine, 3841 Roger Brooke Dr., Fort Sam Houston, TX 78234.Email: brit.long@yahoo.com.Conflicts ofInterest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias.No author has professional or financial relationships with any companies that are relevant to this study.There are no conflicts of interest or sources of funding to declare.Copyright: © 2019 Long et al.This is an open access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) License.See: http://creativecommons.org/ licenses/by/4.0/Volume 20, no.6: November 2019 Diagnosis of Acute Heart Failure in the ED: An Evidence-Based Review Long et al. executive summary.A report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the International Society for Heart and Lung Transplantation; Endorsed by the Heart Failure Society of America.Circulation.Koe L, Bais R, et al.Effect of NT-proBNP testing on diagnostic certainty in patients admitted to the emergency department with possible heart failure.Ann Clin Biochem.2011;48(Pt3):212-7.57.Wang CS, FitzGerald JM, Schulzer M, et al.Does this dyspneic patient in the emergency department have congestive heart failure?JAMA.2005;294(15):1944-56.58.Wong GC, Ayas NT.Clinical approaches to the diagnosis of acute heart failure.Curr Opin Cardiol.2007;22(3):207-13.59.Martindale JL, Wakai A, Collins SP, et al.Diagnosing acute heart failure in the emergency department: a systematic review and meta-analysis.Acad Emerg Med.2016;23(3):223-42.60.Abraham WT, Fonarow GC, Albert NM, et al.OPTIMIZE-HF Investigators and Coordinators.Predictors of in-hospital mortality in patients hospitalized for heart failure: insights from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF).J Am Coll Cardiol.2008;52(5):347-56.61.Fonarow GC, Adams KF Jr, Abraham WT, et al.ADHERE Scientific Advisory Committee Study Group and Investigators.Risk stratification for in-hospital mortality in acutely decompensated heart failure: classification and regression tree analysis.JAMA.2005;293(5):572-80.62.Ambrosy AP, Vaduganathan M, Mentz RJ, et al.Clinical profile and prognostic value of low systolic blood pressure in patients hospitalized for heart failure with reduced ejection fraction: insights from the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) trial.Am Heart J. 2013;165(2):216-25.63.Opasich C, Rapezzi C, Lucci D, et al.Precipitating factors and decisionmaking processes of short-term worsening heart failure despite "optimal" treatment (from the INCHF Registry).Am J Cardiol.2001;88(4):382-7.64.Ambardekar AV, Fonarow GC, Hernandez AF, et al.Get with the Guidelines Steering Committee and Hospitals.Characteristics and in-hospital outcomes for nonadherent patients with heart failure: findingsfrom Get with the Guidelines-Heart Failure (GWTG-HF).Am Heart J.
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