How to differentiate between heart failure with reduced ejection fraction (HFrEF) due to antihypertensive medication and septic shock due to cellulitis in a patient with a history of hypertension and presenting with hypotension?

Differentiating HFrEF Due to Antihypertensive Medication vs. Septic Shock from Cellulitis

In a patient with hypotension, history of hypertension, and cellulitis, septic shock should be presumed and treated immediately with IV fluids and antibiotics, as this represents a life-threatening emergency requiring urgent intervention, whereas medication-induced HFrEF decompensation typically presents more gradually and would not explain acute hypotension in the context of active infection. 1

Clinical Presentation Patterns

Septic Shock from Cellulitis

• Acute onset with rapid deterioration over hours to days, not weeks 1
• Fever, rigors, and confusion are hallmark features of sepsis 1
• Tachycardia (HR >100 bpm) with warm or cold extremities depending on early vs. late shock 1
• Elevated lactate (>2 mmol/L) strongly suggests septic shock 1
• Elevated white blood cell count and inflammatory markers (procalcitonin may help confirm bacterial infection) 1
• Visible cellulitis with erythema, warmth, and tenderness of affected limb 1

HFrEF Decompensation from Antihypertensive Medications

• Gradual onset over days to weeks with progressive dyspnea and fatigue 1
• Pulmonary congestion with crackles, elevated jugular venous pressure, and peripheral edema 1
• Elevated natriuretic peptides (BNP >100 pg/mL or NT-proBNP >300 pg/mL) 1
• Cardiomegaly on chest X-ray in most cases 1
• Reduced LVEF (<40%) on echocardiography 1

Critical Diagnostic Algorithm

Step 1: Immediate Assessment (Within Minutes)

• Check vital signs and lactate immediately - lactate >2 mmol/L with hypotension suggests septic shock 1
• Assess for signs of infection - fever, rigors, visible cellulitis, confusion 1
• ECG is rarely normal in acute HF but does not rule out concurrent sepsis 1

Step 2: Laboratory Evaluation (Within 1 Hour)

• Natriuretic peptides (BNP/NT-proBNP): Normal levels (<100 pg/mL BNP or <300 pg/mL NT-proBNP) make acute HF unlikely 1
• Troponin elevation can occur in both conditions but is more common with acute HF 1
• Procalcitonin helps differentiate bacterial infection from cardiac causes 1
• Complete blood count, creatinine, and liver function tests 1

Critical caveat: Elevated natriuretic peptides can occur in sepsis, renal dysfunction, and other non-cardiac conditions, so they do not automatically confirm HF 1

Step 3: Imaging (Timing Depends on Stability)

• Chest X-ray should be obtained early - cardiomegaly and pulmonary edema suggest HF, but up to 20% of acute HF patients have normal chest X-rays 1
• Bedside echocardiography is mandatory in hemodynamically unstable patients to assess LVEF and exclude mechanical complications 1
• Pocket ultrasound can rapidly assess for B-lines (pulmonary edema) and cardiac function 1

Treatment Approach Based on Clinical Scenario

If Septic Shock is Suspected (Most Likely in Your Scenario)

Immediate treatment takes priority over complete diagnostic workup 1

• Crystalloid fluid resuscitation: 30 mL/kg bolus over first 3 hours for hypotension with suspected sepsis 1
• Broad-spectrum IV antibiotics within 1 hour of recognition 1
• Reassess frequently for signs of fluid overload (increasing oxygen requirement, new crackles, worsening edema) 1
• If fluid overload develops: Reduce fluid rate and consider vasopressors (norepinephrine first-line) rather than continuing aggressive fluids 1

If HFrEF Decompensation is Suspected

• Diuretics are the mainstay for symptomatic relief of congestion 1, 2
• Do NOT discontinue guideline-directed medical therapy (GDMT) for asymptomatic hypotension 1, 3
• For symptomatic hypotension with SBP <90 mmHg: First reduce non-HF blood pressure medications and decrease loop diuretics if no congestion present 1, 3
• Maintain beta-blockers, ACE inhibitors/ARNIs, MRAs, and SGLT2 inhibitors unless shock is present 1, 2

Key Distinguishing Features

Favors Septic Shock

• Acute presentation (<24-48 hours) 1
• Fever >38°C or hypothermia <36°C 1
• Lactate >4 mmol/L 1
• Normal or low natriuretic peptides 1
• Warm extremities initially (early septic shock) 1

Favors HFrEF Decompensation

• Subacute presentation (days to weeks) 1
• Orthopnea and paroxysmal nocturnal dyspnea 1
• Significantly elevated natriuretic peptides 1
• Pulmonary edema on chest X-ray 1
• Known reduced LVEF or new wall motion abnormalities 1

Common Pitfalls to Avoid

Do not delay antibiotics and fluid resuscitation while waiting for echocardiography if sepsis is suspected - this is a time-critical emergency 1

Do not assume hypotension is solely due to HF medications in a patient with active cellulitis - infection is the more immediately life-threatening cause 1

Do not withhold GDMT in stable HFrEF patients with asymptomatic low blood pressure (SBP 90-100 mmHg), as these medications reduce mortality 1, 3

Both conditions can coexist - a patient with chronic HFrEF can develop septic shock, requiring treatment of both conditions simultaneously 1

When Both Conditions May Coexist

In patients with known HFrEF who develop sepsis:

• Treat sepsis aggressively with fluids and antibiotics 1
• Monitor closely for fluid overload with clinical exam and consider bedside ultrasound 1
• Use vasopressors earlier rather than excessive fluid if signs of congestion develop 1
• Continue GDMT unless cardiogenic shock develops 1, 2