April 21, 2021, via Shahriar Lahouti and Mojtaba Chardoli. Last updated: Dec 22, 2021
- Clinical Scenario
- Definition and clinical classification of AHFS
- Framework for pathophysiology of AHFS
- Clinical picture and diagnosis
- Differential diagnosis
- General approach to AHFS
- Going further
Acute Heart Failure Syndrome (AHFS) has a broad clinical and hemodynamic spectrum resulting from a multitude pathophysiologic disease processes. Some patients are critically ill and emergent identification and resuscitation are crucial. Appropriate management of these patients depends on pathophysiology of the ‘AHFS” which is notably different among various phenotypes of heart failure (see here).
Flash pulmonary edema (aka Hypertensive cardiogenic pulmonary edema, crashing pulmonary edema , acute hypertensive heart failure etc) is a general clinical term used to describe a particularly dramatic form of acute decompensated heart failure 1. Due to the central role of sympathetic overdrive in the pathophysiology of this subset of patients, sympathetic crashing acute pulmonary edema (SCAPE) 2 is a better terminology for understanding the syndrome of rapid onset, life-threatening pulmonary edema 3.
In this post, the conceptual framework for pathophysiology of AHFS is briefly discussed first and then SCAPE is explored in detail. This post is not about:
- Cardiogenic shock
- Mild-moderate decompensated heart failure
- Less common types of heart failure with unique physiology e.g. acute valvular regurgitation (more on this here part 1 and part 2), hypertrophic cardiomyopathy, dynamic LV outflow tract obstruction.
- Right ventricular failure (more on this here)
A 60-year-old female with a past history of hypertension and heart failure presented to the ED with acute dyspnea and chest tightness. She appeared anxious and diaphoretic, sitting bolt upright. Her BP was 195/89 mm Hg, PR 143 bpm, RR 32/min, SPO2 88% on HFNC, and temperature 36.5 C. Bilateral basal rales noted. ECG showed sinus tachycardia with nonspecific ST-T changes. Findings in bedside ultrasound were supportive for diagnosis of acute pulmonary edema. How emergent management should proceed with this patient?
#1: Patients with Sympathetic Crashing Acute Pulmonary Edema (SCAPE) are universally fluid-overloaded!
#2: Diuretics play a pivotal role in amelioration of disease processes!
#3: Initiating NTG @ 10-40 mcg/min (low dose) is effective!
Acute heart failure is not a single disease but rather a heterogeneous clinical syndrome with complex pathophysiologic processes and different overlapping pathologic mechanism 4; hence called “Acute Heart Failure Syndrome” in this post ( a variety of terms have been used in literature e.g. acute decompensated heart failure and so on). By enlarge, AHFS can be defined as the new onset or recurrence of symptoms and signs of HF requiring urgent or emergent therapy 5.
The cardinal clinical manifestation of “AHFS” include:
- Clinical Congestion: manifested as pulmonary congestion (pulmonary edema) or systemic congestion (extremities edema)
- End-organ Hypoperfusion: manifested as renal or hepatic dysfunction
While the following clinical classification system (figure 1) does not fully encompass some less common clinical scenarios (e.g. isolated right HF or high output HF), it usefully captures the vast majority of AHFS patients likely to be seen in routine clinical practice. A simplified classification scheme defines three general groups of AHF patients6.
Such phenotypes can occur de novo and in patients with pre-existing chronic heart failure, whether EF is preserved (HFpEF) or reduced (HFrEF).
👉From the hemodynamic perspective, the unique feature common to all phenotypes of “AHFS” is elevated left ventricular diastolic pressure (LVEDP).
One potentially useful framework for understanding the pathophysiology of AHF is to consider it as the result of the interaction of underlying substrate, initiating mechanisms or triggers, and amplifying mechanisms; all of which contribute to a common set of clinical signs and symptoms (primarily related to congestion, end-organ dysfunction, or both) that define AHFS 7 (figure 2).
Substrate: substrate refers to underlying cardiac structure and function. That is to say whether the patient has a pre-existing cardiac dysfunction or not.
- The underlying substrate may be one of normal ventricular function, for example, patients without a prior history of HF who develop AHFS because of sudden changes in ventricular function from an acute insult such as extensive MI or acute myocarditis.
👉Most patients with AHF have a substrate of chronic compensated HF, who then decompensate and present with AHFS.
Triggers: Initiating mechanisms vary according to, and interact with, the underlying substrate and may be cardiac or extracardiac (appendix 1).
- For patients with normal substrate (normal myocardium), a substantial insult to cardiac performance (e.g., acute myocarditis) is required to lead to the clinical presentation of AHF.
- For patients with abnormal substrate at baseline (asymptomatic LV dysfunction), smaller perturbations (e.g., poorly controlled hypertension, AF, or ischemia) may precipitate an AHF episode.
Amplifying mechanisms: these perpetuate and contribute to the episode of decompensation and include
- Neurohormonal (e.g. RAAS) and inflammatory activation
- Ongoing myocardial injury with progressive myocardial dysfunction
- Worsening renal function
- Peripheral vascular dysfunction (e.g., peripheral vasoconstriction)
For more detailed schema see appendix 2.
SCAPE is the most dramatic form of acute decompensated heart failure. The underlying pathophysiologic mechanisms are similar to other phenotypes of “AHFS”. However there are notable differences between these two.
👉Important distinguishing features of SCAPE are abnormal vasoconstriction secondary to sympathetic activation, exaggerated degree of pulmonary RAAS, and decline in NO production. In other words, a different triggering milieu is superimposed on a different substrate as (figure 3):
- Substrate: The underlying cardiac function is often preserved EF with diastolic dysfunction secondary to chronic hypertension.
- Triggering mechanisms: Sympathetic overdrive caused by hypertension crisis, anxiety/stress, sympatholytic medications non-adherence, sympathomimetic or other clinical disorder which can result in sympathetic surge.
- Amplifying mechanisms: ongoing LV dysfunction (with increasing LVEDP), alveolar flooding and hypoxemia; all can perpetuate the vicious cycle of sympathetic surge contributing to worsening clinical condition.
Misconception and pitfalls:
Congestion is NOT equal to volume overload.Overemphasis on the role of volume overload in pathogenesis of AHFS leads to mismanagement of SCAPE subtype. There are two distinct pathways that can result in pulmonary congestion in acute decompensated heart failure:
#1. Cardiac failure: Progressive worsening of cardiac function results in activation of neurohormonal mechanisms (e.g. RAAS’) where excess volume can accumulate gradually and contributes to decompensated heart failure.
#2. Vascular failure: Results from an abrupt redistribution of fluid from the splanchnic and central circulation into the pulmonary vasculature rather than an accumulation of volume. This is the principal mechanism of pulmonary congestion in “SCAPE” (figure 4):
- Recent studies have shown that LVEDP can rise without precipitous change in body weight 8 9. Several vascular abnormalities including arterial stiffness, abnormal vascular compliance and peripheral vasoconstriction (high SNS tone 13 and dysregulated vascular tone due to ↓nitric oxide production) contribute to central “Redistribution of Volume”. This results in pulmonary venous congestion and edema 10 11 12.
The clinical observation that vasodilator treatment can improve dyspnea in SCAPE without significant diuresis has led to the concept that vascular mechanisms play pivotal role in pathophysiology of the disease and can lead to increased diastolic filling pressures in the setting of minimal total body volume changes.
SCAPE is the extreme end of the spectrum of acute pulmonary edema. Rapid “Volume Redistribution” (from peripheral vascular system to pulmonary circulation) associated with sympathetic surge causes dramatic onset and rapid progression of dyspnea (minutes to hours) to life-threatening pulmonary edema, giving the emergency physicians a narrow time window to intervene and improve patient outcome.
The patient may or may not have a previous diagnosis of HF. Oftentimes patients have a history of poorly controlled hypertension 14 and poor adherence to medication. This condition may less often be triggered by atrial arrhythmias and ACS 6.
- History of recurrent episodes of SCAPE may be present.
Symptoms and signs
Patients present with rapid onset (often ≦6 h) of extremely severe respiratory distress.The core clinical findings include 22
- Tachypnea (RR ≧30) and dyspnea.
- Hypertension (SBP >160 and/or MAP>120 mmHg).
- Clinical features of sympathetic activation
- Diaphoresis 😓, pallor.
- Extensive bilateral rales are present on chest examination 3.
- POCUS shows diffuse B-lines.
Other classic symptoms and signs of AHFS may not be present (e.g. cardiomegaly, lower extremity edema, worsening exercise intolerance, weight gain, hepatic congestion, jugular venous distention) 15.
Diagnosis of “SCAPE” is clinical and is not often a dilemma. However, keep in mind that any form of severe respiratory failure (see below) may lead to distress and hypertension. Hallmarks of SCAPE is rapid improvement with therapy. In uncertain situations, it is reasonable to initiate treatment for SCAPE while simultaneously investigating for other problems.
EKG: Evidence of left atrial enlargement and LV hypertrophy is sensitive (non-specific) for chronic LV dysfunction.
- May suggest an acute tachydysrhythmia as the cause of HF or aid in the diagnosis of acute MI or likelihood of a prior MI.
- The presence of a left bundle branch block is a marker for diminished LV systolic function.
Bedside ultrasound (echocardiography): Bedside ultrasound will show diffuse B lines on exam. Cardiac evaluation often reveals diastolic dysfunction, and “IVC” may actually show fluid depletion.
👉Keep in mind that due to sympathetic surge and severe vasoconstriction, intravascular volume is redistributed centrally and accumulated within the lung interstitium and alveoli.
✓CBC, comprehensive metabolic panel (poor perfusion can lead to electrolyte abnormalities and acute renal or hepatic insufficiency).
✓Troponin: High values can lead to the diagnosis of an MI as a triggering event; note that more sensitive troponin assays will frequently be positive at the baseline in many patients with chronic HF 16 (more on this here).
✓TSH if thyroid disease suspected.
✓BNP levels are unhelpful (POCUS is a superior test 17) and it should be interpreted with caution in acute HF presentations. It can be elevated in a variety of other conditions.
Patients with SCAPE present with undifferentiated respiratory distress (more on this here). However diagnosis is straightforward when history, clinical signs and symptoms are integrated and supported by other diagnostic findings in POCUS (see figure 5) and EKG.
Despite critically ill appearance of the patients and severe respiratory distress; they often respond rapidly to appropriate vasodilator medication and noninvasive ventilatory support.
- Pulmonary embolism: Pre-test probability for thromboembolic disease and POCUS can be helpful (more on this here).
- Noncardiogenic pulmonary edema (NCPE): It is invariably associated with an underlying disease, which may or may not be readily apparent. The diagnosis of NCPE often depends on pretest probabilities: acute respiratory distress in a patient with possible source of infection (i.e. UTI) or pancreatitis should raise the strong possibility that the respiratory failure is due to NCPE. Echocardiography can support diagnosis of CPE, if mitral annular plane systolic excursion (MAPSE) is < 10mm (more on this here).
- Pneumonia: It has a more subacute course. More importantly systolic blood pressure is not usually skyrocketed.
- Asthma: Lung ultrasound is potentially helpful as it reveals absence of B-lines in asthma.
General initial stabilization and management of patients with acute heart failure (AHFS) is shown below (figure 6).
The hallmark of SCAPE is rapid deterioration, however aggressive treatment can rapidly reverse this process and will avoid intubation, ICU admission, and morbidity 18. The key principles of management strategy include
- Promptly apply positive pressure noninvasive ventilation
- Aggressive control of hypertension
- Close monitoring of patient’s clinical status
Immediately apply BiPAP. The provided end-expiratory positive pressure (EPAP) will reduce preload and afterload, exerting a physiologic effect to vasodilators and also improve oxygenation (recruitment).
- Start at a low pressure (e.g. IP 12 cm, EP 6 cm). Up-titrate IP/EP by 2cm H2O as tolerated, with a goal of increasing the expiratory pressure (e.g. titrate up to ~18 cm/15 cm).
- The maximal safe pressure is not precisely defined, but pressures above ~20 cm may increase the risk of gastric insufflation.
2. Aggressive control of hypertension
The keystone of management involves reducing the afterload (see pathophysiology of SCAPE above).
Blood pressure target: There is no well-defined BP goal, but a common target may be to reduce the systolic BP to <140-160 mmHg rapidly. However, the MAP or diastolic BP may actually be superior targets, since they are more closely correlated with systemic vascular resistance 23.
- The most commonly used vasodilators are nitrate. Nitrates are the first line, with nitroglycerin being the most common. At moderate doses, nitroglycerin mostly affects the preload, but at high IV infusion doses ( >250 μg/min), arteriolar dilation occurs, which works to reduce afterload 19. Appropriately dosed nitro drip will turn off sympathetic surge of SCAPE patients.
- It is a safe agent with a short half-life (<10 minute), which makes it easy to titrate.
- Caution is warranted for the use of nitrates with low SBP, bradycardia,recent use of phosphodiesterase type 5 inhibitors (eg, sildenafil, tadalafil) within the past 48hrs and elevated intracranial pressure.
- Most importantly, nitroglycerin at these high doses should be titrated with the physician at the bedside. In cases of hypotension, stop or decrease the dose, because hypotension is usually transient.
- In case of refractory hypertension, other medications that can be used are
- Clevidipine: Start at 1-2 mg/h. Double q2min until BP begins approaching target, then titrate by smaller increments q5-10min. Dose range is 1-32 mg/h. Clevidipine is the preferred agent, due to its shorter half-life and stronger evidentiary basis in acute heart failure.
- Nicardipine: Start at 5 mg/hr. If BP is above target, increase by 2.5 mg/hr every 15-30 min, to a maximum rate of 15 mg/hour. Nicardipine has a longer half-life, so there is a risk of causing overshoot hypotension.
- ACE inhibitors and ARBs: can be used in refractory hypertension, if renal function allows. The main drawback is nephrotoxicity. These agents may not be ideal for patients with acute kidney injury, or multimorbid patients with numerous active medical problems.
- Enalaprilat IV (1.25 mg, may repeat q15min to a maximal dose of 5 mg) can be an option.
- ⚠️Contraindicated agent: Beta-blockers. Remember that beta-blockers will impair pump function, so they are generally contraindicated in the context of acute decompensated cardiogenic pulmonary edema (including SCAPE).
👉Nitroglycerin administration- High dose nitroglycerin regimen
- Rational: High dose nitroglycerin for SCAPE patients has been shown to be associated with lower rates of mechanical ventilation, improvement in blood pressure, shorter length of stay, and lower rates of ICU admission (moderate quality evidence) 20, although exact protocol may vary.
- Preparation: Standard nitroglycerin mix is 200 mcg/ml (premixed solutions available), or you can mix 50mg of nitroglycerin with 250mL of 0.9% NS or 5% Dextrose. In order to give for example 400mcg/min for 2 minute, you need 4cc of this solution and give it over 2 minute.
- Loading dose: Start with an initial loading dose of IV nitroglycerine of ~600-1000 mcg (based on initial BP) 22. This may be provided in one of two ways:
- Maintenance infusion: Infusion may be initiated at a rate of ~100mcg/min 22.
- Titration: If BP isn’t controlled promptly (remains the same or increasing): up-titrate the infusion rate by 20mcg/minevery 10min till SBP starts decreasing. Note that very high doses (e.g. 800 mcg/min) may be required for limited periods of time, to break the cycle of progressive hypertension.
- Continue the appropriate dose of nitroglyceine until the resolution of symptms (any of two) 22:
- Decrease in RR by 25% of initial RR.
- RR <24/min
- SBP <140-160
- Subjective improvement of symptoms
- Refractory hypertension: If hypertension is refractory to 800 mcg/min nitroglycerine, then consider the addition of nicardipine, clevidipine, IV enalaprilat, captopril, and/or fentanyl.
- Weaning off nitroglycerine: Generally the SCAPE will start resolving rapidly (within minutes to a couple of hours), causing the BP to decrease. Watch the blood pressure closely and down-titrate the nitroglycerine infusion accordingly, to avoid hypotension.
- Reduce the NTG infusion rate by 20mcg/min every 10min, and stop.
💊Remember that sublingual nitroglycerin takes time to peak and has a bioavailability of around 30%-60%; which makes it unsuitable for such an emergent condition.
Diuretics may have a role (if subsequent hemodynamic evaluation reveals volume overload) but are usually not necessary during the initial stage of resuscitation.
👉Remember that SCAPE patient are not volume overloaded (often volume depleted) despite significant life-threatening pulmonary edema.
👉Diuretic is not effective in initial phase of resuscitation for two reasons:
- First, severe vasoconstriction and poor renal perfusion hamper diuretic access to renal tubules for exerting its effects.
- Second, patients with SCAPE are often volume depleted. Overdiuresis can further contribute to volume depletion, and volume depletion can cause stress response and sympathetic surge.
If subsequent hemodynamic evaluation (based on history, physical exam and POCUS) suggests volume overload, one can administer furosemide 40-80 mg IV.
3.Close monitoring of clinical status 👁🗨
If SCAPE is treated appropriately, it will break rapidly. The vicious spiral will stop and the patient will improve. The most obvious way to tell this is happening is often when the BP starts to drop precipitously. Management involves:
- Rapidly down-titrate the nitroglycerine infusion and BiPAP pressures (while watching for recurrent SCAPE).
- Consider any triggers of SCAPE and treat them (e.g. nonadherence to antihypertensives, volume overload).
- SCAPE patients frequently end up to be intubated and admitted to the ICU, if not appropriately managed. This requires understanding the pathophysiology of the disease.
- Congestion does not equal volume overload. Despite dramatic pulmonary edema, oftentimes they are volume depleted. The key pathophysiologic mechanism for pulmonary congestion is sympathetic overdrive and consequent central redistribution of volume.
- These patients respond rapidly to BiPAP and High dose nitroglycerin.
- Low-moderate dose nitroglycerin as well as diuretics do NOT work in these patients.
- High dose nitroglycerin turns off sympathetic surge and perfectly works in reducing afterload. Be prompt and aggressive and do not leave the room untill the patient becomes stabilized.
- Sympathetic Crashing Acute Pulmonary Edema (SCAPE) EMCrit
- Flash Pulmonary Edema (EM:RAP)
- Emergencies with a Side of Hypertension (EMCrit)
- Hypertensive emergency(IBCC)
- SCAPE (FOAMcast)
- Morning Report Pearls (CORE EM)
- HF, APE
Post Peer Reviewed By Darab Zohri. MD.
The copyright of the header image: Eur Heart J Suppl, Volume 18,December 2016.
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