Can cardiomyopathy cause heart failure with preserved ejection fraction (HFpEF)?

Yes, Specific Cardiomyopathies Can Cause HFpEF

Yes, certain cardiomyopathies are recognized causes of heart failure with preserved ejection fraction (HFpEF), though most HFpEF cases result from hypertensive heart disease and cardiometabolic conditions rather than primary cardiomyopathies. 1

Understanding the Relationship

The 2023 ACC Expert Consensus explicitly categorizes specific cardiomyopathies as "HFpEF mimics" that warrant disease-directed therapy rather than standard HFpEF management 1. This distinction is critical because these conditions require specialized treatment approaches.

Cardiomyopathies That Cause HFpEF Include:

Infiltrative/Restrictive Cardiomyopathies:

• Cardiac amyloidosis (both AL and transthyretin types) - starts as restrictive cardiomyopathy with preserved systolic function and diastolic heart failure, progressing to systolic dysfunction in advanced stages 2
• These present with increased LV wall thickness, elevated filling pressures, and preserved EF initially

Hypertrophic Cardiomyopathy (HCM):

• Characterized by unexplained LV hypertrophy with preserved or hyperdynamic EF 1, 3
• Can present with LV outflow tract obstruction
• Requires CMR if diagnosis uncertain on echocardiogram 1

Other Structural Causes:

• Pericardial disease (constrictive pericarditis)
• Valvular heart disease (particularly aortic stenosis, mitral regurgitation)
• High-output heart failure states 1

Diagnostic Algorithm

When evaluating a patient with dyspnea, edema, and EF ≥50%, follow this stepwise approach 1:

Step 1: Apply Universal Definition of HF

• Confirm symptoms/signs of HF
• Elevated natriuretic peptides OR objective evidence of congestion
• EF ≥50%

Step 2: Exclude Noncardiac Mimics Look for primary noncardiovascular causes:

• Kidney disease (check urinalysis for proteinuria)
• Liver disease (abdominal ultrasound)
• Chronic venous insufficiency
• Pulmonary disease

Step 3: Identify Cardiac Mimics Requiring Specific Workup

Red flags suggesting cardiomyopathy rather than typical HFpEF 1:

• Increased LV wall thickness (>1.5 cm) with preserved EF
• Musculoskeletal issues: carpal tunnel syndrome, lumbar spinal stenosis (suggests amyloidosis)
• Neuropathy (sensory or autonomic)
• Low BMI with heart failure (typical HFpEF patients are obese)
• Absence of typical risk factors (hypertension, diabetes, obesity)

Step 4: Targeted Testing Based on Clinical Suspicion

For suspected cardiac amyloidosis 1:

1. Monoclonal protein screen (serum/urine immunofixation electrophoresis and serum free light chains)
2. Technetium pyrophosphate scan (if monoclonal screen negative)
3. Endomyocardial biopsy (if monoclonal screen positive)

For suspected hypertrophic cardiomyopathy 1, 3:

1. Detailed 3-generation family history
2. CMR if echocardiogram uncertain
3. Genetic testing when appropriate

Clinical Context Matters

The 2023 ACC guidelines emphasize that demographic and comorbid risk factors are crucial in distinguishing true cardiomyopathy-related HFpEF from typical HFpEF 1.

Typical HFpEF patient profile:

• Elderly (especially women)
• Hypertension
• Obesity (BMI >30)
• Diabetes
• Atrial fibrillation
• Chronic kidney disease

Cardiomyopathy-related HFpEF profile:

• May be younger
• Lower BMI
• Extracardiac manifestations (neuropathy, carpal tunnel)
• Disproportionate LV wall thickness relative to blood pressure history
• Family history of cardiomyopathy or sudden death

Treatment Implications

This distinction is not academic—it fundamentally changes management 1:

• Infiltrative cardiomyopathies require disease-specific therapies (e.g., tafamidis for transthyretin amyloidosis, chemotherapy for AL amyloidosis)
• Hypertrophic cardiomyopathy may require septal reduction therapy, mavacamten, or specific management of outflow obstruction 3
• Standard HFpEF therapies (SGLT2 inhibitors, diuretics) may be insufficient or inappropriate as primary treatment

Common Pitfalls to Avoid

1. Don't assume all patients with dyspnea, edema, and preserved EF have typical HFpEF - always consider alternative diagnoses 1

2. Don't miss amyloidosis - it's underdiagnosed and treatable. Any patient with increased wall thickness and HFpEF warrants screening 1, 2

3. Don't perform exhaustive testing on every HFpEF patient - use clinical judgment based on history, physical exam, and initial echocardiogram to guide further workup 1

4. Don't delay specialist referral when cardiomyopathy is suspected - these patients benefit from specialized centers 1, 3

The 2016 ESC guidelines note that HFrEF typically occurs with dilated cardiomyopathy, while HFpEF more commonly involves increased LV wall thickness and left atrial enlargement 4. However, specific cardiomyopathies like infiltrative and hypertrophic types clearly cause HFpEF and require recognition for optimal management.