Acute heart failure (AHF) is a complex clinical syndrome characterized by the rapid onset or worsening of heart failure symptoms and signs, frequently requiring urgent medical intervention and hospitalization. It stands as a leading cause of unplanned hospital admissions, particularly among individuals over the age of 65. The diverse clinical presentations of AHF, influenced by patient history, pre-existing cardiac conditions, and the nature of intravascular congestion, necessitate a thorough and nuanced approach to differential diagnosis. This article provides an in-depth exploration of the Acute Heart Failure Differential Diagnosis, aiming to enhance clinical decision-making and optimize patient management in English-speaking healthcare settings.
Clinical Approach to Acute Heart Failure: Navigating the Diagnostic Landscape
Managing acute heart failure effectively hinges on a systematic clinical approach that acknowledges the heterogeneity of this syndrome. A ‘one-size-fits-all’ strategy is inadequate; instead, a personalized approach is crucial, guided by a detailed assessment of the patient’s clinical profile. This involves considering the presence and type of congestion (pulmonary and/or systemic), perfusion status, underlying pathophysiology, and any precipitating factors. Furthermore, pre-existing cardiac conditions, comorbidities (such as renal or hepatic dysfunction, pulmonary disease, and bleeding risk), potential iatrogenic effects of interventions, and patient preferences must all be integrated into a tailored treatment plan.
For differential diagnosis, understanding the clinical profile is paramount. Patients are often categorized based on congestion and perfusion status at admission. The majority, approximately 70%, present with a ‘warm-wet’ profile, indicating congestion without hypoperfusion. Around 20% exhibit a ‘wet-cold’ profile, characterized by both congestion and hypoperfusion. A small fraction, less than 1%, presents with a ‘dry-cold’ profile, signifying hypoperfusion without congestion. The remaining patients fall into a ‘dry-warm’ profile, lacking both congestion and hypoperfusion, which may suggest the need for medical therapy optimization.
A more granular characterization of AHF involves assessing the pattern of fluid distribution—whether it is predominantly pulmonary, systemic, or both—and the presence or absence of systemic hypoperfusion. This categorization is clinically significant as it directly informs therapeutic strategies.
De Novo vs. Acutely Decompensated Heart Failure: Diagnostic Considerations
Differentiating between de novo AHF and acutely decompensated heart failure (ADHF) is a crucial step in the differential diagnosis. Patients presenting with de novo HF, meaning new-onset heart failure without prior diagnosis, often have fewer comorbidities compared to those with ADHF. Their presentation is frequently dramatic, manifesting as cardiogenic shock or acute pulmonary edema, often triggered by acute cardiac ischemia, severe valvular lesions (typically regurgitant), inflammatory processes like myocarditis, or exposure to toxins. While their acute presentation may be severe, these patients often have a potentially better prognosis compared to those with ADHF, provided the underlying cause is addressed. The primary mechanism in de novo HF is usually an acute hemodynamic disturbance stemming from left ventricular systolic dysfunction.
In contrast, ADHF occurs in patients with pre-existing chronic heart failure. These individuals commonly present with pulmonary and/or peripheral congestion, left ventricular dysfunction (which may also involve the right ventricle), and maladaptive neurohormonal activation. ADHF represents an exacerbation of a chronic condition where repeated episodes progressively diminish functional reserve. Right ventricular dysfunction and frequent heart failure hospitalizations are often indicative of advanced disease stages and serve as ‘red flags’ for adverse outcomes. Risk stratification tools like INTERMACS profiles incorporate factors such as frequent HF hospitalizations as indicators of high-risk status. Recurrent ventricular arrhythmias also signal advanced disease and are considered significant risk modifiers.
Differentiating these two scenarios is crucial for accurate acute heart failure differential diagnosis and management. De novo HF may necessitate a focus on identifying and treating the acute trigger (e.g., acute myocardial infarction), while ADHF management requires addressing both the acute exacerbation and optimizing the long-term management of chronic heart failure.
To aid in the diagnostic process, the acronym CHAMPIT (Acute Coronary Syndrome, Hypertensive Emergency, Arrhythmias, Acute Mechanical Cause, Pulmonary Embolism, Infection, Tamponade) is a useful framework for considering specific causes of AHF. Ruling out these etiologies is essential before tailoring management based on the clinical presentation and phenotype of AHF.
Table 1. Clinical, Echocardiographic, and Hemodynamic Markers to Assess Congestion and Hypoperfusion
| Clinical Manifestations | Echocardiographic Findings | Hemodynamic Parameters |
|---|---|---|
| Congestion | ||
| Bilateral lung crackles or rales | Elevated LV or RV filling pressures | Increased CVP (>12 mmHg) |
| Elevated Jugular Venous Pressure (JVP) and/or hepatojugular reflux | Dilated and non-collapsing Inferior Vena Cava (IVC) | Increased PCWP (>15 mmHg) |
| Peripheral edema | Lung B-lines | |
| Hepatomegaly | Altered Doppler signals of hepatic, portal, and renal veins (VExUS) | |
| Orthopnea | Pleural effusion | |
| Pleural effusion | ||
| Low Cardiac Output or Hypoperfusion | ||
| Narrow pulse pressure | Low Left Ventricular Outflow Tract Velocity Time Integral (LVOT VTI) | Increased arterial lactate (>2 mmol/L) |
| S3 heart sound | Reduced cardiac index (<2.2 L/min/m²) | |
| Sensation of impending doom | Reduced cardiac power output | |
| Alteration of mental status | Reduced cardiac power index | |
| Cold and clammy extremities, cyanosis | Occult hypoperfusion | |
| Oligoanuria | Pulmonary artery O2 saturation <60% | |
| Delayed capillary refill | Arteriovenous delta CO2 > 6 mmHg |
Cardiogenic Shock: The Extreme End of Acute Heart Failure
Cardiogenic shock (CS) represents the most severe manifestation within the spectrum of AHF syndromes. It arises from a primary cardiovascular dysfunction leading to inadequate cardiac output (CO), resulting in life-threatening tissue hypoperfusion. This hypoperfusion triggers impaired tissue oxygen metabolism and hyperlactatemia, which, if unaddressed, can progress to multi-organ dysfunction and death.
The Society for Cardiovascular Angiography and Interventions (SCAI) has proposed a refined classification system for cardiogenic shock, utilizing a 3-axis model that considers shock severity, phenotype and etiology, and risk modifiers. This classification, validated across multiple studies involving over 20,000 patients, demonstrates a strong correlation between SCAI shock stage and mortality risk, providing a structured approach to acute heart failure differential diagnosis in its most critical form.
The SCAI Shock Classification encompasses five stages:
- Stage A (At Risk): Patients with conditions predisposing to cardiogenic shock, such as large acute myocardial infarction (AMI) or prior infarction, or those presenting with AHF symptoms.
- Stage B (Beginning Shock): Patients showing early hemodynamic instability, indicated by hypotension or tachycardia, but without overt signs of hypoperfusion.
- Stage C (Classic Shock): Patients with manifest hypoperfusion requiring pharmacological or mechanical intervention to restore adequate perfusion.
- Stage D (Deteriorating Shock): Patients whose initial support strategies are failing, evidenced by worsening hemodynamics and increasing lactate levels.
- Stage E (Extremis Shock): Patients in actual or impending circulatory collapse, often with severe metabolic derangements (e.g., lactate >8 mmol/L, pH <7.2).
The pathophysiology of cardiogenic shock is multifaceted, involving primary pump dysfunction, hemodynamic alterations, microcirculatory dysfunction, systemic inflammatory response syndrome, and potentially multi-organ failure. The most common hemodynamic profile in CS is ‘wet and cold’, although a significant proportion (around 30%) may present with a euvolemic ‘dry and cold’ profile. Notably, up to 20% of CS cases can present as ‘wet and warm’, often associated with systemic inflammatory response syndrome or mixed shock, characterized by low systemic vascular resistance (SVR), fever, and leukocytosis. Clinical inflammation is observed in 20–40% of CS patients, contributing to reduced SVR, while infections complicate up to 30% of cases, often related to vascular access or bacterial translocation.
In contemporary practice, non-ischemic etiologies are increasingly recognized as the predominant cause of cardiogenic shock requiring admission to cardiac intensive care units (CICU). A critical diagnostic challenge is identifying and appropriately managing patients with subtle signs of hemodynamic compromise, such as tachycardia or relative hypotension without overt hypoperfusion, or those with normotensive hypoperfusion. These patients face higher mortality risks compared to those in SCAI stage A and may even have a worse prognosis than those in SCAI stage C, as their condition can deteriorate rapidly if unrecognized. The SCAI stage B classification includes patients with hypotension or hypoperfusion (lactate 2–5 mmol/L or elevated liver enzymes), encompassing those with end-organ damage despite normal blood pressure (normotensive shock).
The SCAI Shock classification’s three-axis model emphasizes the importance of differentiating between acute and acute-on-chronic presentations. Compensatory mechanisms in chronic heart failure can mask the severity of acute decompensation, potentially leading to underestimation of risk, particularly in early SCAI stages (A and B).
Research has highlighted that hypoperfusion, even in the context of normal blood pressure, is a critical predictor of mortality. Patients with hypoperfusion (defined by elevated lactate, oliguria, or rising creatinine) have increased mortality compared to those with hypotension but preserved perfusion. This underscores the importance of recognizing hypoperfusion in normotensive patients and integrating this assessment into clinical decision-making for acute heart failure differential diagnosis and management in cardiogenic shock. Assessment of patients with shock and pre-shock states should be multi-parametric, integrating clinical, hemodynamic, and laboratory parameters, as no single variable is definitive.
Table 2. Hemodynamic Profiles of Cardiogenic Shock Subtypes
| Hemodynamic Variables | Normotensive Hypoperfusion | Hypotensive Normoperfusion | LV Dominant Shock | RV Dominant Shock | Biventricular Shock |
|---|---|---|---|---|---|
| SBP, mmHg | >90 | <90 | <90 | <90 | <90 |
| CVP, mmHg | Variable | Variable | >14 | >14 | >14 |
| PCWP, mmHg | Variable | Variable | >18 | Variable | >18 |
| CVP/PCWP | Depends on LV/RV involvement | Depends on LV/RV involvement | >0.86 | >0.86 | >0.86 |
| Pulmonary artery pulsatility index | Depends on RV involvement | Depends on RV involvement | >1.5 | <1.5 | <1.5 |
| CI, l/min/m2 | <2.2 | <2.2 | <2.2 | <2.2 | <2.2 |
| SVR, dynes-s/cm5 | >1600 | 800–1600 | 800–1600 | 800–1600 | 800–1600 |
| CPO, W | Variable | Variable | Low | Low | Low |
BiV: biventricular; CPO: cardiac power output; CVP: central venous pressure; LV: left ventricular; PAD: pulmonary artery diastolic pressure; PAS: pulmonary artery systolic pressure; PAPi: pulmonary artery pulsatility index; PCWP: pulmonary capillary wedge pressure; RA: right atrial pressure; RV: right ventricular; SBP: systolic blood pressure; SVR: systemic vascular resistance.
Invasive Hemodynamic Assessment: The Role of the Swan-Ganz Catheter
In complex cases of acute heart failure, particularly when differentiating between left, right, or biventricular dysfunction, or in cardiogenic shock, clinical, echocardiographic, and laboratory assessments may prove insufficient. In these scenarios, invasive hemodynamic assessment, typically using a pulmonary artery catheter (Swan-Ganz catheter), can be invaluable for refining the acute heart failure differential diagnosis and guiding management.
The pulmonary artery catheter allows for direct measurement of critical hemodynamic parameters, including central venous pressure (CVP), pulmonary artery systolic and diastolic pressures, pulmonary capillary wedge pressure (PCWP), cardiac output (and cardiac index), and central venous oxygen saturation. From these direct measurements, derived indices such as systemic and pulmonary vascular resistances, left ventricular stroke work, and cardiac power output (CPO) can be calculated. For right ventricular function assessment, specific indices like RV stroke work, CVP/PCWP ratio, and pulmonary artery pulsatility index (PAPi) are also obtainable.
The use of a Swan-Ganz catheter facilitates a more precise evaluation of intracardiac pressures, enabling differentiation between left-sided, right-sided, or biventricular congestion, and aiding in phenotyping cardiogenic shock subtypes. Studies have shown that right-sided congestion is associated with increased mortality compared to left-sided congestion or euvolemia, and elevated right atrial pressure is a significant predictor of mortality in cardiogenic shock.
Recent advancements include the correction of cardiac power index (CPI) by incorporating right atrial pressure (RAP), termed CPIRAP. This refined index, calculated as CPIRAP = (MAP − RAP) × CI/451, improves prognostic accuracy, particularly in patients with SCAI B-D cardiogenic shock, by better identifying patients with severe intravascular congestion that may be missed by traditional CPI calculations. A CPIRAP cut-off of 2 has been identified as indicative of higher in-hospital mortality risk in this population.
Machine learning analysis has further delineated distinct phenotypes within cardiogenic shock based on hemodynamic profiles. Three primary phenotypes have emerged:
- Noncongested Shock: Characterized by relatively lower heart rate and filling pressures, with comparatively higher cardiac output and blood pressure. This phenotype represents a less severe form of shock with lower in-hospital mortality.
- Cardiorenal Shock: Associated with intermediate mortality, this phenotype exhibits more frequent left ventricular failure, elevated PCWP, and worsening renal function, indicating renal involvement secondary to shock.
- Cardiometabolic Shock: This most severe phenotype is marked by elevated lactate and right atrial pressure (RAP), liver damage, low blood pressure and cardiac output, suggesting significant venous congestion and multi-organ involvement, and carries the highest mortality risk.
These phenotype distinctions align with the understanding that elevated CVP poses a greater risk of organ damage. Hypotension in the context of elevated CVP, particularly in right ventricular or biventricular shock, can rapidly compromise abdominal organ perfusion, leading to a ‘double-hit phenomenon’ of multiple organ failure (renal, hepatic, and ischemic bowel failure). This critical scenario necessitates immediate interventions to increase blood pressure with vasopressors and reduce CVP.
Hemodynamics-Based Medical Therapy in Acute Heart Failure and Cardiogenic Shock
The therapeutic approach to AHF should be structured around three key axes: management of pulmonary congestion (gas exchange), systemic congestion, and tissue perfusion.
Pulmonary congestion, a common feature in AHF, can manifest dramatically as acute cardiogenic pulmonary edema. This condition arises from a sudden increase in pulmonary capillary hydrostatic pressure, leading to fluid accumulation in the lungs and acute respiratory failure. Immediate treatment includes oxygen therapy and, in cases of severe respiratory distress, non-invasive ventilation (CPAP or NIV) or, in critical situations, orotracheal intubation. Non-invasive positive pressure ventilation can reduce the need for intubation and improve survival in selected patients by reducing LV preload and afterload, decreasing myocardial oxygen demand, and promoting fluid displacement from the alveoli.
Systemic congestion, the most prevalent phenotype in ADHF, results in elevated CVP and potential end-organ dysfunction due to reduced organ perfusion pressure. The primary therapeutic intervention is aggressive decongestion with early diuretic administration, guided by urine output monitoring. In cases of loop diuretic resistance, dose escalation and diuretic combinations (thiazides, acetazolamide, metolazone, tolvaptan) should be considered. Vasodilators, particularly nitroglycerin, can be beneficial in reducing CVP and improving decongestion. Renal replacement therapy is reserved for diuretic-refractory volume overload.
Tissue hypoperfusion represents the most critical AHF phenotype, where inadequate cardiac output leads to impaired tissue perfusion and end-organ damage. In cardiogenic shock, initial management includes assessing volume status; fluid boluses may be appropriate in euvolemic patients without overt congestion. Inotropes and vasopressors are often necessary to support blood pressure and improve cardiac output. The choice of vasoactive agents should be tailored to the clinical context, considering factors such as beta-blocker use, RV dysfunction, myocardial ischemia, renal function, and sepsis.
Mechanical circulatory support (MCS) devices play a crucial role in managing severe AHF and cardiogenic shock. The intra-aortic balloon pump (IABP) is useful in ADHF-CS and as a bridge to more advanced therapies. For more severe cases, extracorporeal membrane oxygenation (ECMO) or percutaneous ventricular assist devices (pVADs) may be necessary, with device selection guided by the presence of left, right, or biventricular failure and respiratory compromise.
Hemodynamic monitoring with a pulmonary artery catheter is particularly valuable in managing patients receiving MCS, guiding therapy escalation and de-escalation, and assessing candidacy for durable LVAD or heart transplantation. Continuous hemodynamic assessment allows for real-time evaluation of treatment effectiveness and facilitates the weaning process from circulatory support.
Table 3. Medical Management of Acute Heart Failure According to Clinical Profile
| Clinical Profile | Hemodynamic Characteristics (Typical) | Medical Management Strategies |
|---|---|---|
| Warm-Dry | Normal SVR, Normal PCWP, Normal CVP | Up-titrate Guideline-Directed Medical Therapy (GDMT) |
| Wet-Warm | Normal SVR, Increased CVP and/or PCWP | Diuretics (Renal Replacement Therapy if refractory volume overload), Consider vasodilators |
| Cold-Dry | High SVR, Normal PCWP, Normal CVP | Fluid challenge (if no volume overload signs), Inotropes, Vasodilators (if SBP sufficiently high) |
| Wet-Cold | High SVR, Increased CVP and/or PCWP | Inotropes, Vasopressors (if BP persistently low), Diuretics (RRT if refractory volume overload or severe lactic acidosis), Vasodilators (if SBP sufficiently high), Temporary Mechanical Circulatory Support |
Transitioning to Chronic Management: GDMT and Residual Congestion
Once the acute phase of heart failure is stabilized, transitioning to chronic management and implementing guideline-directed medical therapy (GDMT) becomes paramount. GDMT typically includes an angiotensin receptor-neprilysin inhibitor (ARNI) or ACE inhibitor/ARB, beta-blocker, mineralocorticoid receptor antagonist (MRA), and sodium-glucose cotransporter-2 inhibitor (SGLT2i). Drug selection should be tailored to the patient’s clinical scenario and comorbidities. Initiation of neurohormonal inhibitors should occur when blood pressure and renal function are stable. In patients with low blood pressure, starting with MRA and SGLT2i, followed by beta-blockers and then ACEi/ARB/ARNI, may be appropriate. Beta-blocker initiation should be deferred if there are concerns about low cardiac output or significant residual congestion.
Residual congestion at discharge remains a significant issue, affecting over 30% of HF patients and associated with increased 1-year mortality. Factors such as tricuspid regurgitation, diabetes, anemia, and higher NYHA class increase the risk of residual congestion. Conversely, beta-blocker use at admission, de novo HF presentation, or cardiovascular procedures during hospitalization are associated with a lower risk.
SGLT2 inhibitors, such as empagliflozin, have demonstrated early and effective decongestive effects in AHF patients, associated with improved clinical outcomes and symptom scores.
Conclusions
Acute heart failure is a significant and increasingly prevalent public health challenge, marked by high morbidity and mortality. A standardized, yet personalized, approach is essential for managing HF patients, with rapid identification of high-risk features being critical. Clinical, echocardiographic, and laboratory evaluations are typically sufficient for risk stratification and guiding therapy. However, in complex cases like cardiogenic shock with right ventricular involvement or when mechanical circulatory support is needed, pulmonary artery catheterization should be considered to refine diagnosis and guide treatment strategies. Early recognition of right ventricular dysfunction is vital, as elevated CVP is a strong predictor of adverse outcomes. Upon clinical stabilization, the primary goal should be the implementation and optimization of GDMT to reduce the risk of subsequent heart failure events and mortality.
