Article, Cardiology

Misconceptions in acute heart failure diagnosis and Management in the Emergency Department

a b s t r a c t

Introduction: Acute heart failure accounts for a significant number of emergency department (ED) visits, and the disease may present along a spectrum with a variety of syndromes.

Objective: This review evaluates several misconceptions concerning heart failure evaluation and management in the ED, followed by several pearls.

Discussion: AHF is a heterogeneous syndrome with a variety of presentations. Physicians often rely on natriuretic peptides, but the evidence behind their use is controversial, and these should not be used in isolation. Chest ra- diograph is often considered the most reliable imaging test, but bedside ultrasound (US) provides a more sensi- tive and specific evaluation for AHF. Diuretics are a foundation of AHF management, but in pulmonary edema, these medications should only be provided after vasodilator administration, such as nitroglycerin. Nitroglycerin administered in high doses for pulmonary edema is safe and effective in reducing the need for intensive care unit admission. Though classically dopamine is the first vasopressor utilized in patients with hypotensive cardiogenic shock, norepinephrine is associated with improved outcomes and lower mortality. Disposition is complex in pa- tients with AHF, and risk stratification tools in conjunction with other assessments allow physicians to discharge patients safely with follow up.

Conclusion: A variety of misconceptions surround the evaluation and management of heart failure including clin- ical assessment, natriuretic peptide use, chest radiograph and US use, nitroglycerin and diuretics, vasopressor choice, and disposition. This review evaluates these misconceptions while providing physicians with updates in evaluation and management of AHF.

  1. Introduction

Acute heart failure is a heterogeneous syndrome and one of the most common reasons for hospitalization in the U.S. for those older than 65 years [1-4]. It is commonly associated with coronary disease, renal disease, atrial fibrillation, diabetes, and hypertension [1,2,5]. This dis- ease accounts for over 650,000 ED visits annually in the U.S., and close to 80% of patients with AHF are first evaluated in the ED, with the major- ity admitted [5-7]. Patients may present in a variety of ways, including gradual decline with worsening symptoms over several weeks, hyper- tensive pulmonary edema, or cardiogenic shock.

Emergency medicine evaluation and management typically focuses on Initial resuscitation based on patient hemodynamics and degree of illness. Testing typically includes electrocardiogram, imaging, and labo- ratory assessment, with management including airway support, vasodi- lators, and/or diuretics [8-12]. Disposition is typically inpatient

* Corresponding author.

E-mail addresses: [email protected], (B. Long), [email protected] (E.J. Chin).

admission, but this is a complex decision requiring consideration of multiple factors.

Though emergency physicians are well versed in the evaluation and management of this condition, with multiple sets of guidelines available [8-12], there are several components that remain misunderstood. This review seeks to provide emergency physicians with an improved un- derstanding of evaluation and management in heart failure by address- ing several common misconceptions.

  1. Discussion

This review will focus on several components of evaluation, manage- ment, and disposition in the ED by investigating misconceptions in AHF.

Misconception: Natriuretic peptide testing is routinely helpful in diag- nosing or excluding AHF

Natriuretic peptides include B-type Natriuretic Peptide and NT-proBNP. These molecules are cardiac neurohormones functioning

https://doi.org/10.1016/j.ajem.2018.05.077 0735-6757/

in volume and sodium homeostasis produced in the cardiac muscula- ture due to myocyte stretch, which may occur in AHF [8,10,13]. A pre- cursor molecule, proBNP, is released with myocyte stretch, which is enzymatically cleaved to NT-proBNP and BNP [13-17]. The half-life of BNP is close to 20 min, while NT-proBNP’s half-life is 3-6 times that of BNP’s [13-17]. These molecules increase sodium and water excretion, increase peripheral vasodilation, and decrease activity of the renin an- giotensin aldosterone system (RAAS) [8,10].

Natriuretic peptides are often used in AHF. An American College of Emergency Physicians (ACEP) clinical policy provides level B recom- mendations that with BNP b 100 pg/mL or NT-proBNP b 300 pg/mL, AHF is unlikely, while for BNP N 500 pg/mL or NT-proBNP N 1000 pg/mL, AHF is likely [8]. The 2017 American College of Cardiolo- gy (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 be- hind their use in the ED is controversial.

Pearl: Natriuretic peptides should only be used in conjunction with clinical evaluation, rather than using the test in isolation. Ac- knowledgement of other causes of elevated levels is essential.

Approximately one-quarter of patients with dyspnea will fail to demonstrate definitive levels of the biomarker, creating difficulty in in- terpretation of the test [13-20]. One of the first observational studies in- cluded 1586 patients with dyspnea, finding sensitivity of 90% for BNP of 100 pg/mL, with specificity 76% [18]. Authors stated BNP levels were more accurate than any history or examination finding. However, emer- gency physicians were correct in their diagnosis of AHF in over 95% of cases if they were sure of the diagnosis, and they were correct 92% of the time if they were sure AHF was not the cause of symptoms [18]. An- other analysis suggested that emergency physicians had a sensitivity of 49% and specificity of 96% for diagnosis, while BNP 100 pg/mL had a sen- sitivity of 90% and specificity of 73% [19]. Though authors state BNP may have corrected physician diagnosis, there is no discussion for patients in whom BNP was incorrect. Cardiology diagnosis, the gold standard, was 90% accurate for diagnosis of AHF, and cardiologists disagreed on diag- nosis in 11% of cases [19]. The RED-HOT trial suggested BNP level was correlated with 90-day mortality and need for readmission in AHF [20]. However, close evaluation of the area under the curve for 90-day outcomes was 0.67 for BNP, which is poor, suggesting no additional benefit [20]. A systematic review and 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 sen- sitivity and specificity 99% and 43%, respectively [21]. Another meta- analysis found sensitivity and specificity of 93.5% and 52.9%, respec- tively, for BNP, and 90.4% and 38.2%, for NT-proBNP, respectively [22]. This meta-analysis suggested BNP levels are better than isolated history and examination findings, but included studies demonstrated several weaknesses including poor gold standard (typically cardiologist opin- ion), and few looked at emergency physician judgment [22]. In summa- ry, observational data suggest BNP and NT-proBNP possess high sensitivities for AHF, but moderate to poor specificity. When emergency physicians are less certain of the diagnosis, natriuretic peptides demon- strate less accuracy, and it is not clear that BNP can outperform clinical judgment.

Randomized controlled trial (RCT) data also differ in outcomes. One

study from 2004 suggested fewer in-hospital admissions and ICU ad- missions, as well as lower cost, when utilizing natriuretic peptides [23]. No differences in mortality or readmission were found; however, physicians in this study were not blinded, and objective outcomes were not different when utilizing BNP. The IMPROVE-CHF study evalu- ated NT-proBNP, with decrease in length of stay by 0.7 h and decreased Total costs [24]. However, no differences in hospitalizations, readmis- sion rate, hospital LOS, or ICU admissions were found, with a nonsignif- icant increase in mortality when using NT-proBNP. A marginal improvement in diagnostic accuracy was found when BNP was added

to clinical assessment, while BNP alone was not better than clinical ge- stalt alone [24]. Another study found decreased hospital LOS (two days), but no difference in hospitalization rate or ED LOS [25]. Several more recent RCTs suggest no difference in clinical outcomes such as mortality, readmission, or hospital LOS [26-30].

Other causes of elevated natriuretic peptides include coronary syn- dromes, valvular heart disease, pericardial disease, atrial fibrillation, cardiac surgery, cardioversion, older age, anemia, renal failure, pulmo- nary hypertension, critical illness, sepsis, and burns [21-23]. Age, gen- der, and body weight/body mass index can affect BNP levels. Due to less myocardial stress, obese patients may demonstrate lower BNP and NT-proBNP [31,32].

In isolation, BNP may outperform other history and examination fea- tures for AHF diagnosis, though it may not outperform overall Clinical impression. For patient-oriented outcomes, studies are not definitive, as several suggest a decrease in admission, cost, and LOS, while others suggest no difference in these outcomes or patient-centered outcomes such as mortality [26-30]. Cutoffs vary, and there is significant lack of blinding and spectrum bias present in studies evaluating BNP.

Misconception: chest radiograph is the go-to imaging test in AHF

Patients presenting with suspected AHF undergo a variety of tests, including chest X-ray. This test is an important component of the overall assessment of patients with suspected AHF, with a variety of findings [8-12,22]. However, chest X-ray findings are not definitive [22]. Kerley B-lines demonstrate a sensitivity of 9.2% and specificity 98.8%, intersti- tial edema sensitivity 31.1% and specificity 95.1%, cephalization sensitiv- ity 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].

Though the test may be specific, it is not sensitive, as close to 20% of chest X-rays demonstrate no findings of AHF [9-12,22]. Chest X-ray may suggest an alternative diagnosis such as chronic obstructive pul- monary disease, pneumonia, or pneumothorax.

Pearl: A more valuable means of diagnosis for pulmonary edema associated with AHF is ultrasound.

Point-of-care ultrasound is a vital tool in the diagnosis and management of several critical conditions, including AHF. Reliance on chest X-ray and laboratory assessment may result in Delays in diagnosis and treatment, and POCUS can provide clinicians with a means of more reliable and rapid diagnosis, while also considering potential etiologies and mimics of AHF. POCUS may include evaluation of several compo- nents, including the lungs, heart, and Inferior vena cava , with sev- eral protocols available [22,33,34]. Lung US alone with the presence of

>=3B lines in >=2 bilateral thoracic lung zones possesses a positive likeli- hood ratio (+LR) of 7.4, sensitivity approaching over 90%, and specific- ity 92.7% for pulmonary edema, while the absence of B lines possesses a negative likelihood ratio (-LR) of 0.16 [22,35-37]. Figs. 1 and 2 demon- strate B lines suggestive of pulmonary edema. The number of B lines correlates with AHF severity [38,39]. Measurement of intravascular vol- ume is completed through assessment of the IVC diameter and percent- age change in diameter while breathing [22,33]. However, specific numbers vary for IVC collapsibility index, including 20%-50%. IVC col- lapsibility b33% is associated with sensitivity approaching 80% for vol- ume overload, with specificity 81%-87% [39-42]. IVC assessment is complicated by other conditions such as tricuspid regurgitation, pulmo- nary hypertension (pulmonary embolism), and right ventricular myo- cardial infarction [22,39-42]. Assessment of cardiac function can assist, measuring the inward movement of the interventricular septum and in- ferior wall of the LV in systole and degree of excursion of the anterior MItral valve leaflet in diastole [22,33,34]. A reduction in LV function on POCUS by emergency clinicians demonstrates a sensitivity for AHF 77-83% and specificity 74-90% [22,39,40]. A quantitative measure in- cludes E-point septal separation (EPSS), which is the distance between

Fig. 1. – B lines in the presence of pulmonary edema.

the anterior leaflet of the mitral valve and ventricular septum during systole. An EPSS measurement N7 mm suggests ejection fraction (EF) b 50% [43-45]. A diastolic filling restrictive pattern with pulsed Doppler analysis of mitral inflow demonstrates a +LR 8.3, sensitivity 80.6%, and specificity 80.6%, though this specific measurement is not typically com- pleted without US Fellowship training [22,44,45]. Overall, lung US for the presence of >=3 B lines in >=2 bilateral thoracic lung zones is reliable and sensitive for pulmonary edema [22,35-37]. Assessment of cardiac function with POCUS can also assist.

Misconception: diuretics are the mainstay of therapy in all cases of AHF

Diuretics are considered a key component in heart failure therapy in acute decompensation and chronic therapy. They are also a major factor in guidelines [8-12,46-48]. The AHA/ACC and international guidelines state diuretics are first-line medications in the management in AHF, with the goal of improving congestion and obtaining euvolemia at the lowest dose possible [9-12,48]. The most common diuretics include fu- rosemide, torsemide, and bumetanide [9-12,48,49]. Furosemide is pri- marily eliminated through the kidneys, while the latter two medications undergo hepatic elimination [49,50]. Intravenous (IV) ad- ministration in AHF is the recommended route, as this route possesses greater bioavailability, allowing for diuresis to begin within 30-60 min. Guidelines typically recommend an IV dose that is equal

Fig. 2. – B lines in the presence of pulmonary edema.

to or greater than the patient’s daily maintenance dose [8-12]. ACEP provides Level B recommendations to “Treat patients with moderate- to-severe pulmonary edema resulting from acute heart failure with fu- rosemide in combination with nitrate therapy”, followed by a Level C recommendation that “(1) Aggressive diuretic monotherapy is unlikely to prevent the need for endotracheal intubation compared with aggres- sive nitrate monotherapy. (2) Diuretics should be administered judi- ciously, given the potential association between diuretics, worsening renal function, and the known association between worsening renal function at index hospitalization and long-term mortality.” [8]

However, AHF is a heterogeneous syndrome, rather than one dis- tinct entity, with patients demonstrating differences in hemodynamic status (including systolic blood pressure (SBP)) and degree of systemic versus pulmonary congestion [8-12,48,49]. In patients with SBP ranging from 100 to 140 mmHg, diuretics may improve systemic congestion. However, in patients with acute pulmonary edema and hypertension, diuretics are more complicated, with better options available.

Pearl: In acute pulmonary edema with hypertension, nitroglycerin and noninvasive positive pressure ventilation should be first-line therapies before diuresis.

In acute pulmonary edema (APE), N50% of patients do not have true volume overload, but rather volume distribution, with movement of fluid into the lungs [51-53]. Zile et al. found patients with APE demon- strated no significant increase in dry weight during their exacerbation [52], and another study found approximately half of patients have less than a two pound increase during their episode of APE [53]. Fluid shifts from other body compartments such as the splanchnic circulation into the pulmonary circulation may result in pulmonary edema. Patients re- ceiving furosemide first may experience decreased LV function, in- creased ventricular filling pressures, and increased systemic vascular resistance through activation of the neurohormonal system [51-57]. The medication can also decrease glomerular filtration rate (GFR), po- tentially even further decreasing diuresis [54-57]. In this setting, harm may result with diuretic therapy if the patient is not truly volume overloaded.

Diuretics are beneficial in normotensive patients with systemic con- gestion from true volume overload, which includes signs and symptoms such as ascites and extensive peripheral edema accumulating over an extended period of time [8-12]. However, in hypertensive APE with AHF and little to no evidence of systemic congestion, nitroglycerin and noninvasive positive pressure ventilation should be adminis- tered [8,57-60]. These measures improve Work of breathing, decrease preload, and can decrease afterload, and in particular, NIPPV is associat- ed with reduced need for intubation (number needed to treat of 8) and mortality (number needed to treat of 13) [57-60]. The utility of nitro- glycerin will be discussed in detail later.

Pearl: A variety of diuretic strategies may be utilized in patients with systemic congestion, and ultrafiltration may improve diuresis in patients refractory to IV diuretics.

Parenteral diuretics possess relatively short half-lives, and doses may be repeated to target adequate urine output in patients with nor- mal SBP and systemic congestion. Repeat boluses of furosemide can be provided every 4-6h [9-12,48,49]. The AHA/ACCF Heart Failure Guide- lines recommend an initial IV dose equivalent or greater than the home dose given bolus or continuously [9-11,48]. If this does not improve symptoms, the dose of Loop diuretic can be increased, or a second di- uretic added (thiazide) [9-12]. Bolus versus continuous infusion of di- uretic is controversial. The DOSE trial evaluated four groups: low dose continuous infusion (home dose administered continuously over one day), high dose continuous infusion (2.5 X home dose administered continuously over one day), low dose bolus (home dose divided into two daily boluses), and high dose bolus (2.5 times daily home dose di- vided into two daily doses) loop diuretics [61]. Comparisons included bolus versus continuous and low-dose versus high-dose [61]. The trial found high-dose loop diuretics may improve symptoms but increase serum creatinine (Cr), while continuous versus Intermittent boluses

were not clinically significant [61]. Meta-analysis suggested similar re- sults [62]. If diuresis with IV loop diuretics fails, ultrafiltration (UF) is an alternative method to remove further congestion in hypervolemia [63-67]. Literature suggests greater net weight and fluid loss with UF compared to standard diuretic therapy, but no change in mortality [64-67].

Misconception: the safest means of providing nitroglycerin IV is to be- gin with small doses and titrate to relief of symptoms to ensure patient safe- ty in those with pulmonary edema

Nitrates cause vasodilation through activation of guanylyl cyclase on nitrate-derived nitric oxide, increasing cyclic guanosine 3?,

-5? monophosphate (cGMP) bioavailability and cGMP-dependent pro- tein kinases activation [68,69]. Ultimately, intracellular calcium de- creases, resulting in venous and arterial vasodilation, reducing biventricular filling pressures, systemic arterial blood pressure, and pul- monary vascular resistance [70,71]. In AHF, the most common nitrates are nitroglycerin and nitroprusside. Nitroglycerin is more commonly used in AHF, as it improves Coronary blood flow, reduces myocardial is- chemia, and has relatively no effect on neurohormones [7-9,68-73]. Ni- troprusside reduces coronary blood flow, increases myocardial ischemia, and increases neurohormones [72,73].

The greatest benefit is in those with pulmonary edema due to sys- temic improvements in preload and fluid redistribution. Current guide- lines from the AHA recommend vasodilator use in addition to diuretics in those who fail to respond to diuretics alone, or in patients with severe fluid overload without hypotension [9-12,48]. The ESC recommends use in patients with SBP N 110 mmHg, and the Heart Failure Association of the ESC, European Society of Emergency Medicine, and Society of Aca- demic Emergency Medicine recommend providing nitroglycerin to those with SBP N 110 mmHg [9-12,74,75]. ACEP’s clinical guidelines pro- vide a Level B recommendation to “administer intravenous nitrate ther- apy to patients with acute heart failure syndromes and associated dyspnea.” [8]. Nitroglycerin is typically initiated at initial IV dose of 10-20 ug/min, which is increased by 10-20 ug/min until symptom im- provement [8-12,48,60]. Sublingual nitroglycerin can be started first, with 400 ug tablet. However, nitroglycerin is contraindicated in hypo- tension, obstruction of the LV outflow tract, recent use of phosphodies- terase inhibitors, and conditions similar to AHF where vasodilation is not beneficial (COPD). Also, side effects such as headache (20% of pa- tients) and nitrate resistance and tolerance can develop [76-79].

Pearl: Nitroglycerin IV may be provided safely in higher doses, in- cluding bolus or infusion, which will rapidly relieve symptoms.

Nitrates can improve symptoms and hemodynamics, but it is not as- sociated with improved mortality or readmission rate [80-82]. Several studies have evaluated nitrates IV at higher doses (including nitroglyc- erin IV), whether bolus or infusion [83-85]. One of the earlier studies evaluating high dose nitrate therapy was published in 1998 and includ- ed 110 patients with pulmonary edema treated with oxygen, furose- mide, and morphine [60]. Patients were randomized to isosorbide- dinitrate 3 mg IV every 5 min bolus versus isosorbide-dinitrate 1 mg/h infusion. Bolus dose isosorbide-dinitrate was found to be safe and effec- tive in reducing pulmonary edema, while decreasing need for mechan- ical ventilation and myocardial infarction [60]. A 2000 study evaluated bilevel positive pressure airway ventilation versus high dose nitrate therapy (isosorbide-dinitrate 4 mg every 4 min IV) in patients with se- vere pulmonary edema, finding patients receiving high dose nitrates to have lower mortality, need for intubation, and myocardial infarction, though only 40 patients were enrolled [84]. A 2007 nonrandomized open label study evaluated high dose nitroglycerin in patients with SBP N 160 mmHg and pulmonary edema, finding nitroglycerin 2 mg IV every 3 min to be associated with reduced intubation, need for bilevel positive pressure ventilation, and ICU admission [83]. A 2017 retrospec- tive observational cohort study included patients over 18 years with AHF, comparing nitroglycerin bolus (500-2000 ug every 3-5 min),

nitroglycerin infusion (20-35 ug/min), and nitroglycerin bolus plus in- fusion [85]. Authors found decreased ICU admission in the bolus group compared with the other groups. Secondary outcomes included shorter length of stay in the bolus group, with no differences in adverse out- comes (intubation) [85]. At this time, administering nitroglycerin more aggressively at higher doses, whether bolus or infusion, is likely safe and may be associated with reduced need for intubation and need for ICU admission, compared with lower infusion rates. However, further evaluation on its effect on mortality is required, as well as inves- tigation into the potential harms.

Misconception: morphine is safe in AHF and should be provided to the majority of patients with AHF

Morphine was traditionally a key component of therapy in Cardiac conditions including heart failure. It reportedly may reduce preload and heart rate and provide anxiolysis, potentially improving outcomes in AHF through its reduction in myocardial oxygen demand [86-89]. Physiologically, morphine causes depression of the central nervous sys- tem through its effect on opiate receptors, resulting in sedation and an- algesia [86-89]. It may result in anxiolysis, and together with sedation, may decrease sympathetic nervous system activity and reduce cardiac filling pressures and arterial pressures [86-89]. These considerations come from several older trials evaluating 12 dogs, 12 patients with mild pulmonary edema, and 12 patients with acute myocardial infarc- tion [87-89]. A study in 1994 demonstrated relaxation of veins and ar- teries in vitro utilizing dog vasculature [90], and a 2008 in vivo trial utilizing cats demonstrated dose-dependent vasodilation in pulmonary vessels with morphine [91]. A trial including 28 human patients under- going coronary artery bypass surgery from 1979 found morphine in Large doses (0.5 mg/kg) resulted in large reduction in peripheral vascu- lar resistance [92].

Guidelines vary in recommendations concerning morphine [8-12,48,93]. The ESC supports the use of opioids in heart failure, stating morphine 4-8 mg should be considered if the patient has severe anxiety with pulmonary edema, but the HFSA does not include morphine in its 2010 recommendations and states the medication should be used with caution if provided [11,12,48,93]. The ACC/AHA 2013 guidelines do not discuss morphine [9].

Pearl: Morphine may be associated with harm in AHF and does not improve prognosis.

Evidence suggests morphine is associated with worse outcomes when compared to patients not receiving opioids. Morphine can induce myocardial depression with decreased heart rate and cardiac output [94], as well as cause one of the more feared side effects: respiratory de- pression [95]. This effect is primarily dose-dependent, with opioids de- creasing tidal volume and respiratory rate [95,96]. A prehospital study demonstrated 38% of patients receiving morphine and furosemide ex- perienced deterioration, compared with no patients in the control arm [54]. This study is one of five suggesting harm, and these studies were included in a review article from 2008 emphasizing the association of morphine and deterioration [97-101]. An observational study including the ADHERE registry suggested increased need for mechanical ventila- tion, greater length of stay, increased requirement for ICU level care, and higher risk-adjusted mortality [102]. A retrospective study from 2011 including 2336 patients found morphine to be associated with in- creased mortality, though with propensity score matching this associa- tion was not significant [103]. A recent study including 6516 patients found higher 30-day mortality (20% vs. 12.7%), though in-hospital mor- tality and length of stay were not clinically different [104].

The predominant literature consists of observational studies, which suffer from confounding factors. For example, morphine may have been given more frequently to patients with more severe heart failure. Also, determining if morphine was actually associated with increased intubation versus use as a sedative after intubation is difficult to ascer- tain [105]. Though there are confounders, physicians have many other

options to improve preload and afterload in pulmonary edema and AHF, such as NIPPV and nitrate therapy [54,57,58].

Misconception: in patients with cardiogenic shock and SBP b 100 mmHg, dopamine is the most beneficial medication to improve perfusion

Cardiogenic shock in acute decompensated heart failure, defined by low cardiac output and end-organ hypoperfusion, is rarely due to AHF alone (1%-2% of cases), but is associated with poor prognosis and high mortality [106-110]. The most common cause of cardiogenic shock is myocardial infarction, leading to pump failure, increased ventricular end-systolic volume, increased diastolic pressure, decreased blood flow to peripheral organs, and multiple system failure. Other causes of cardiogenic shock include valvular dysfunction, aortic dissection, peri- cardial tamponade, ventricular septal wall rupture, and AHF [106-112]. Treatment of cardiogenic shock involves initial resuscitation and sta- bilization with airway support, vasopressors and inotropes, and ad- dressing the Underlying etiology (reperfusion therapy for myocardial ischemia, emergent surgery, etc.) [106-110]. While arranging for defin- itive treatment, emergency physicians should focus on ensuring organ perfusion. Controversy is present concerning the choice of vasopressor and inotrope [112]. A small fluid bolus is typically recommended (250-500 mL IV). Dobutamine possesses direct beta 1 and beta 2 adren- ergic agonism, and in the setting of normal blood pressure or minimal hypotension, dobutamine starting at 2-3 ug/kg/min IV is recommended [106,112]. However, it may result in hypotension [113-115]. Prior rec- ommendations advised dopamine for SBP 70-100 mmHg, with norepi- nephrine reserved for those with SBP b 70 mmHg [106,112]. Dopamine is typically dosed at 5-10 ug/kg/min IV, with titration to hemodynamic parameters targeting perfusion. Doses N10 ug/kg/min are associated with more alpha-adrenergic effects [112-115]. The dose dependent changes in effect and prior thoughts of improved renal perfusion were reasons for the use of dopamine [112-115]; however, current literature suggests norepinephrine should be used as the first line vasopressor,

with less 28-day mortality and dysrhythmic events.[116,118]

Pearl: Norepinephrine should be used over dopamine in cardio- genic shock with hypotension.

In the setting of cardiogenic shock, guidelines now recommend nor- epinephrine as the medication to reach target mean arterial pressure (MAP), rather than dopamine. Dopamine is limited by its increased risk of dysrhythmias and vasoconstriction at higher doses, which may decrease end organ perfusion [113-115,117,118]. Evidence suggests norepinephrine is associated with improved outcomes including lower mortality and lower risk of dysrhythmia when compared with dopamine, per one meta-analysis [116]. Both dopamine and norepi- nephrine act to increase catecholamine activity and increase systolic blood pressure. Norepinephrine is an endogenous sympathetic agent, which vasoconstricts blood vessels, slightly improves cardiac output, and increases stroke volume [113-115,117,118]. Norepinephrine should be started at 0.5 ug/kg/min and titrated to mean arterial pressure of 60 mmHg. Dopamine is a predrug of norepinephrine and increases con- tractility and heart rate at 2-10 ug/kg/min, while at doses N10 ug/kg/min, vasoconstriction and increased afterload occur [113-115,117,118].

Misconception: almost all patients with heart failure require admission, and risk stratification tools offer little benefit

An important ED decision is the disposition of the patient with AHF. Disposition is complex and challenging due to the heterogeneous na- ture of AHF and wide spectrum of presentations [9-12,119,120]. Other factors include comorbidities, social factors, patient understanding, and ability to follow up. Patients may also not improve with therapy im- mediately, though a brief observation period may assist. Not all ED’s possess the ability to observe patients for an extended time [121,122].

These potential challenges create significant complexity in the disposi- tion decision.

Currently, a small proportion of patients are discharged directly from the ED in the U.S., approximately 16%-20%, with higher numbers in Canada and Europe [123-128]. An important factor is determining whether patients directly discharged from the ED experience higher rates of adverse events compared with admitted patients. Mortality across studies approaches 4% at 30 days, though 1-year mortality can be as high as 20% [124-129]. One study found 30-day rates of adverse outcomes were higher in patients discharged directly from the ED, though numbers of adverse events at 90 days were similar between groups discharged from the ED versus the hospital, and a separate study found similar rates at 7 and 30 days for mortality, though adverse outcomes past 30 days were higher in patients discharged from the ED [125,126]. These studies are subject to many confounders, and examina- tion of these studies suggests failure to follow guideline-directed thera- py and poor follow up as significant predictors of adverse events [9-12,120]. Return visits for AHF are also high, ranging from 20%-35% within 30 days [127,130,131], with N75% of these returns leading to hos- pitalization [132-134].

Pearl: Risk stratification tools may be helpful, but disposition re- mains challenging and requires evaluation of multiple disease aspects.

disease risk stratification tools have been used for a variety of condi- tions such as pneumonia and pulmonary embolism (PE). Several scores have been derived and validated in patients with AHF, though many of these were evaluated in admitted patients [135-143]. Two scores specif- ically have been evaluated in ED patients, including the Ottawa Heart Failure Risk Scale (OHFRS), which is based on 9 or 10 clinical variables [136,144,145]. Another risk score is the Emergency Heart Failure Mor- tality Risk Grade (EHMRG) [136,146]. The OHFRS was evaluated in pa- tients with dyspnea secondary to new or chronic HF after ED intervention [144,145]. It considers history (stroke or transient ischemic attack, intubation for respiratory distress), examination (heart rate on ED arrival >=110, oxygen saturation b 90% on arrival, and heart rate

>= 110 during 3 min walk test/too sick to perform walk test), and inves- tigations in the ED (new ischemic findings on ECG, serum urea

>=12 mmol/L or 33 mg/dL, serum carbon dioxide >=35 mmol/L, troponin

I or T elevated to meet criteria for myocardial infarction, NT-proBNP N5000 ng/L or pg/mL). The rule classifies adverse events as 30-day all- cause mortality or several outcomes within 14 days of the ED visit (intu- bation, ICU admission, myocardial infarction, major cardiovascular pro- cedure, or hospital admission). The initial derivation study included 559 visits over 6 ED’s, followed by validation, with scores of 1, 2, and 3 as threshold for admission demonstrating sensitivities of 95.2%, 80.6%, and 64.5%, respectively [144]. A 2017 prospective validation included 1100 patients, finding scores >=2 demonstrated sensitivity of 91.8% for adverse event, but this Increased admission rates [145]. A score N 2 as threshold for admission reduced admission rates, while demonstrating equivocal sensitivity to other studies [145].

The EHMRG attempts to predict 7-day mortality based on age, SBP, heart rate, oxygen saturation, Cr, potassium, EMS transportation, tropo- nin, active cancer, and whether the patient is taking metolazone [146]. The score was not conducted in patients with ESRD and does not take into account ejection fraction; however, the score demonstrates good c-statistics for the derivation and validation cohorts (0.803) [146]. Other scores have been derived from hospitalized patients with AHF[137-143]. These studies failed to consider patients already discharged from the hospital and also contain factors that may not be available at the time of ED evaluation [136-143].

Though these scores offer several considerations in determining disposition, other factors should be considered in addition. Patients who are hemodynamically unstable, demonstrate ischemia based on biomarker or ECG findings, or require IV nitroglycerin or respiratory support require admission, likely to ICU. If these are not present, the pa- tient should have SBP N 100 mmHg, normal sodium (135-145 mmol/L),

renal function at patient baseline, and room air saturation N92% [9-12,136]. 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 [147-152]. Patients should demonstrate subjective improvement in symptoms, demonstrate stable vital signs, and possess the ability to follow up within 7 days. Patients with these factors in com- bination with the OHFRS or EHMRG scale may be appropriate for dis- charge [136,144-146].

  1. Conclusions

Acute heart failure is one of the most common causes of hospitaliza- tion and presents in a wide spectrum. This heterogeneous spectrum re- quires consideration of several evaluation and management modalities, as it is not straightforward. A variety of misconceptions are present concerning the ED evaluation and management of AHF. Physicians often rely on assessments including laboratory markers and radiograph, but these measures should only be used in conjunction with clinical ge- stalt. Several other conditions can result in elevation of natriuretic pep- tides, and US in the ED is a reliable means of diagnosis. In the setting of pulmonary edema, diuretics should be provided after nitrates and other respiratory support measures. In cardiogenic shock with hypotension, norepinephrine, rather than dopamine, is recommended if a vasopres- sor is needed. Disposition is complex, and risk stratification tools and other markers may allow physicians to safely discharge patients who meet certain criteria, though further study is required.

Conflicts of interest

None.

Acknowledgements

BL and AK conceived the idea for this manuscript and contributed substantially to the writing and editing of the review. EJC assisted with editing and ultrasound images. This manuscript did not utilize any grants, and it has not been presented in abstract form. This clinical re- view has not been published, it is not under consideration for publica- tion elsewhere, its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically with- out the written consent of the copyright-holder. This review does not reflect the views or opinions of the U.S. government, Department of De- fense, U.S. Army, U.S. Air Force, or SAUSHEC EM Residency Program.

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