Which laboratory tests should be ordered for a patient with newly diagnosed heart failure with reduced ejection fraction to evaluate for causes such as Chagas disease, HIV infection, and possible paraproteinemia (including serum protein electrophoresis and urine protein electrophoresis)?

Laboratory Testing for New HFrEF

For newly diagnosed heart failure with reduced ejection fraction, order the following standard labs: complete blood count, urinalysis, serum electrolytes (including calcium and magnesium), BUN, creatinine, glucose, fasting lipid profile, liver function tests, iron studies (serum iron, ferritin, transferrin saturation), and thyroid-stimulating hormone. 1, 2

Standard Initial Laboratory Panel (Class I Recommendation)

The ACC/AHA guidelines provide clear Class I recommendations for initial laboratory evaluation 1, 2:

• Complete blood count - assess for anemia
• Urinalysis - evaluate for proteinuria and renal disease
• Serum electrolytes including sodium, potassium, calcium, and magnesium
• Renal function: BUN and creatinine
• Glucose (fasting) or glycohemoglobin
• Fasting lipid profile
• Liver function tests
• Iron studies: serum iron, ferritin, and transferrin saturation (added in 2022 guidelines) 2
• Thyroid-stimulating hormone - both hyper- and hypothyroidism can cause or exacerbate HF

Selective Testing for Specific Etiologies (Class IIa Recommendation)

HIV Screening

HIV screening is reasonable in selected patients presenting with HF (Class IIa) 1, 3. The guidelines specifically mention HIV as a reasonable screening test, particularly in high-risk patients. While HIV cardiomyopathy typically presents after other HIV manifestations are evident 4, screening should be considered based on:

• Risk factors for HIV exposure
• Geographic considerations
• Unexplained cardiomyopathy in younger patients

Chagas Disease Testing

Chagas serology should be checked in patients with nonischemic cardiomyopathy who have traveled in or immigrated from endemic regions 5. This is particularly important because:

• Chagas affects approximately 20% of patients with HFmrEF in endemic populations 6
• Specific treatment exists (benznidazole or nifurtimox)
• Reactivation can occur in immunocompromised states 7
• Two serologic tests should be performed for confirmation 7

Endemic regions include Central and South America, particularly rural areas.

Protein Electrophoresis (SPEP/UPEP)

SPEP and UPEP are NOT part of routine initial testing but are reasonable when clinical suspicion exists for amyloidosis or other paraproteinemias 1. Order these tests when:

• Clinical features suggest amyloidosis (unexplained HF with preserved wall thickness, neuropathy, nephrotic syndrome)
• Unexplained restrictive cardiomyopathy
• Concurrent nephrotic-range proteinuria

The guidelines classify testing for amyloidosis as Class IIa: "reasonable in patients presenting with HF in whom there is a clinical suspicion" 1. SPEP/UPEP are not mentioned as routine screening tests in any of the major HF guidelines.

Additional Selective Testing

Hemochromatosis Screening

Fasting transferrin saturation is reasonable for screening 1, 4, particularly in:

• Patients of Northern European descent
• Unexplained cardiomyopathy
• Elevated liver enzymes

Magnetic resonance imaging may be needed to confirm iron overload if screening is positive 4.

Rheumatologic and Other Rare Causes

Testing for rheumatologic diseases, pheochromocytoma, or sarcoidosis is reasonable only when clinical suspicion exists 1.

Key Clinical Pitfalls

1. Don't order SPEP/UPEP routinely - These are expensive tests with low yield unless specific clinical features suggest paraproteinemia or amyloidosis
2. Geographic history matters - Always ask about travel to or residence in Chagas-endemic areas
3. HIV screening threshold - Consider broadly in unexplained cardiomyopathy, not just in obviously high-risk patients
4. Iron studies are now standard - The 2022 guidelines elevated iron studies to routine testing 2, as iron deficiency is common and treatable in HF
5. Serial monitoring - Electrolytes and renal function require ongoing monitoring, not just initial assessment 1

Practical Algorithm

Step 1: Order standard panel on ALL patients (CBC, CMP, glucose, lipids, LFTs, TSH, iron studies, urinalysis)

Step 2: Add selective testing based on:

• Chagas serology → if from/traveled to endemic Latin America
• HIV testing → if high-risk or unexplained cardiomyopathy
• SPEP/UPEP → if clinical features of amyloidosis (thick walls + HF, neuropathy, nephrotic syndrome)
• Hemochromatosis → if elevated transferrin saturation on initial labs or Northern European descent with unexplained cardiomyopathy