What is the cause of hypotension in a patient with no peripheral edema or cardiomegaly and an ejection fraction of 33%?

Hypotension in HFrEF Without Volume Overload

In a patient with an ejection fraction of 33% presenting with hypotension but no edema or cardiomegaly, the most likely cause is inadequate cardiac output from systolic dysfunction itself, potentially compounded by excessive guideline-directed medical therapy (GDMT) or other reversible factors such as arrhythmias, valvular disease, or non-cardiac medications. 1

Primary Mechanism: Low Cardiac Output State

The fundamental issue is reduced forward flow from impaired left ventricular systolic function (EF 33%), which directly compromises blood pressure maintenance. 1, 2

• The absence of peripheral edema and cardiomegaly suggests this patient may have adequate compensatory mechanisms without overt volume overload, but the heart cannot generate sufficient cardiac output to maintain normal blood pressure 3, 2
• This represents a low-output state where systolic dysfunction limits stroke volume and thus mean arterial pressure 1

Critical Differential Considerations

1. Medication-Induced Hypotension

The most common modifiable cause in HFrEF patients is excessive or poorly tolerated GDMT (beta-blockers, ACE inhibitors/ARBs, mineralocorticoid receptor antagonists, SGLT2 inhibitors). 1, 4

• Evaluate all blood pressure-lowering medications, including those not indicated for heart failure (calcium channel blockers, alpha-blockers, nitrates) 4
• Consider excessive diuretic dosing even without overt volume depletion, as this can reduce preload excessively and compromise cardiac output 5, 4

2. Arrhythmias

Atrial fibrillation or other arrhythmias can precipitate hypotension by eliminating atrial kick (contributing ~15-20% of ventricular filling), causing irregular RR intervals that reduce cardiac output by approximately 0.8 L/min, and preventing appropriate heart rate adaptation to metabolic demands. 1

• Loss of atrial contraction is particularly detrimental in patients with diastolic dysfunction, which commonly coexists with systolic dysfunction 1

3. Valvular Heart Disease

Severe aortic stenosis or significant mitral/tricuspid regurgitation can cause or worsen hypotension by reducing forward stroke volume and cardiac output. 1

• Aortic stenosis increases afterload and can lead to low ejection fraction with reduced forward flow 1
• Severe mitral or tricuspid regurgitation diverts blood backward, reducing effective cardiac output 1

4. Myocardial Ischemia

Active ischemia or inadequate revascularization in ischemic cardiomyopathy (the most common cause of HFrEF) can worsen systolic function and precipitate hypotension. 1, 6

• Hypertrophied or failing hearts have reduced coronary flow reserve and increased sensitivity to ischemic injury 1

5. Orthostatic Hypotension

Autonomic dysfunction is common in HFrEF patients, particularly elderly individuals, causing postural drops (≥20 mmHg systolic or ≥10 mmHg diastolic within 2-5 minutes of standing). 1

• Prevalence ranges from 6-30% in elderly hypertensive patients and is exacerbated by GDMT 1

6. Hypovolemia

Despite no peripheral edema, intravascular volume depletion from over-diuresis, poor oral intake, or gastrointestinal losses can occur. 5, 4

• Check for orthostatic vital signs, elevated BUN/creatinine ratio, and hyponatremia 5

Diagnostic Approach

Systematically evaluate reversible causes before attributing hypotension solely to cardiomyopathy: 1, 4

• Medication review: Identify all blood pressure-lowering agents, particularly non-HF medications that can be discontinued 4
• Volume status assessment: Check for orthostatic hypotension, jugular venous pressure, lung examination, and weight trends 5, 4
• Rhythm evaluation: Obtain ECG and consider ambulatory monitoring to detect arrhythmias, particularly atrial fibrillation 1
• Valvular assessment: Echocardiography to evaluate for severe aortic stenosis or significant regurgitant lesions 1
• Ischemia evaluation: Consider stress testing or coronary angiography if ischemic cardiomyopathy is suspected or known 6
• Laboratory testing: Electrolytes (particularly sodium and potassium), renal function, and natriuretic peptides 5, 2

Management Strategy

The 2025 ESC Heart Failure Association consensus provides a structured approach: 1

If Symptomatic or Severe Hypotension (SBP <80-90 mmHg):

1. First, reduce or stop non-HF medications that lower blood pressure (calcium channel blockers, alpha-blockers, nitrates) 4
2. Reduce loop diuretic dose if no signs of congestion are present 5, 4
3. Maintain GDMT with class I indications (beta-blockers, ACE inhibitors/ARBs/ARNI, mineralocorticoid receptor antagonists, SGLT2 inhibitors) unless management appears urgent 1, 4
4. Consult heart failure specialist before stopping or reducing evidence-based HF medications 4

Address Specific Reversible Causes:

• Arrhythmias: Rate control or cardioversion for atrial fibrillation; consider cardiac resynchronization therapy (CRT) if bundle branch block is present (CRT typically increases BP by ~5%) 1
• Valvular disease: Transcatheter aortic valve replacement (TAVR) for severe aortic stenosis can increase SBP by 15±31 mmHg; transcatheter edge-to-edge repair (TEER) for severe mitral/tricuspid regurgitation improves forward flow 1
• Ischemia: Revascularization (CABG preferred over PCI in multivessel disease with HFrEF) 6

Critical Pitfalls to Avoid

• Do not automatically discontinue GDMT based on asymptomatic low blood pressure alone, as these medications improve mortality even in patients with low BP 1, 4
• Do not assume volume overload is absent simply because peripheral edema is not visible; pulmonary congestion can exist without peripheral edema 5
• Do not overlook orthostatic hypotension, which requires standing blood pressure measurements 1
• Do not miss atrial fibrillation, as loss of atrial kick can cause acute clinical deterioration in patients with reduced EF 1

Prognostic Context

While low blood pressure in HFrEF is associated with worse prognosis (2.5-fold increased risk of cardiovascular death or HF hospitalization at SBP <80 mmHg), treatment with GDMT weakens this association, emphasizing the importance of maintaining evidence-based therapies whenever possible. 1