When should other cardiomyopathies, such as hypertrophic (HCM) or restrictive cardiomyopathy, be considered in adults with heart failure with preserved systolic function and a history of hypertension, diabetes, or other cardiovascular risk factors?

When to Consider Other Cardiomyopathies in HFpEF

You should actively investigate for hypertrophic cardiomyopathy (HCM) or restrictive cardiomyopathy in any patient with heart failure and preserved ejection fraction who presents with specific red flags: disproportionate left ventricular hypertrophy (wall thickness >15mm), restrictive filling pattern on echocardiography, marked biatrial enlargement without significant valvular disease, or heart failure symptoms that seem excessive relative to the degree of hypertension or other risk factors present. 1

Primary Clinical Scenarios Requiring Investigation

Unexplained Left Ventricular Hypertrophy

• Suspect HCM when wall thickness exceeds what would be expected from hypertension alone (typically >15-20mm), particularly if hypertrophy is asymmetric or involves the septum disproportionately 1
• The presence of LV hypertrophy with relatively preserved cavity size (end-diastolic dimension <45mm) in a patient with severe heart failure symptoms should raise suspicion for HCM rather than simple hypertensive heart disease 2
• Transthoracic echocardiography is the primary imaging modality to identify and classify cardiomyopathy type, including hypertrophic, dilated, restrictive, and arrhythmogenic forms 1

Restrictive Physiology on Doppler Assessment

• A restrictive filling pattern (E/A ratio >2, deceleration time <150ms) with preserved ejection fraction strongly suggests either restrictive cardiomyopathy or advanced HCM 3, 4
• Marked biatrial enlargement disproportionate to the degree of ventricular dysfunction is a hallmark feature of restrictive cardiomyopathy 4
• These patients often have heart failure symptoms at rest or with minimal exertion despite normal or near-normal ejection fraction 1

Young or Middle-Aged Patients with Severe Symptoms

• Heart failure with preserved systolic function occurring in patients under age 60 without adequate explanation from hypertension or coronary disease warrants cardiomyopathy evaluation 2, 3
• Nonobstructive HCM with preserved systolic function can present with advanced heart failure requiring transplant consideration, representing an under-recognized subset 2
• These patients may progress more rapidly to advanced heart failure than those with obstructive HCM or systolic dysfunction 3

Specific Red Flags by Cardiomyopathy Type

Hypertrophic Cardiomyopathy Indicators

• Family history of sudden cardiac death, HCM, or unexplained heart failure in young relatives 1, 5
• Disproportionate symptoms relative to blood pressure control—patients with well-controlled hypertension who remain severely symptomatic 1
• Dynamic left ventricular outflow tract obstruction (though 48% of HCM patients with heart failure are nonobstructive with preserved systolic function) 3
• Presence of systolic anterior motion of the mitral valve or mitral regurgitation on echocardiography 1

Restrictive Cardiomyopathy Indicators

• Suspect infiltrative disease (amyloidosis, sarcoidosis, hemochromatosis) when there is: 1
  • Increased ventricular wall thickness with a "sparkling" or granular appearance on echocardiography
  • Low voltage on ECG despite increased wall thickness
  • Peripheral neuropathy, renal dysfunction, or other systemic manifestations
• Endomyocardial fibrosis patterns or hypereosinophilic syndrome history 6
• Rapid progression of symptoms despite optimal medical therapy for presumed diastolic dysfunction 5

The Role of Atrial Fibrillation

• Atrial fibrillation is present in 64% of HCM patients who develop advanced heart failure and often precipitates clinical decompensation 3
• New-onset atrial fibrillation in a patient with HFpEF and unexplained LV hypertrophy should prompt thorough cardiomyopathy evaluation 3
• Rate control is essential in these patients, as they are highly dependent on atrial contribution to ventricular filling 1, 7

When Standard HFpEF Features Don't Fit

Disproportionate Diastolic Dysfunction

• Elevated LV end-diastolic pressure or pulmonary capillary wedge pressure (>20mmHg) with only mild-to-moderate hypertrophy suggests intrinsic myocardial disease rather than hypertensive heart disease 2
• Patients requiring heart transplant evaluation despite preserved ejection fraction (≥50%) represent a distinct subset requiring cardiomyopathy diagnosis 2

Absence of Typical HFpEF Risk Factors

• The vast majority of HFpEF patients have hypertension, and most have LV hypertrophy on echocardiography 1
• When heart failure with preserved systolic function occurs without hypertension, diabetes, obesity, or coronary disease, alternative cardiomyopathies must be excluded 1
• Younger patients (under 65) with HFpEF are less likely to have the typical elderly female phenotype and warrant investigation for primary cardiomyopathy 1, 8

Diagnostic Approach Beyond Standard Echocardiography

Advanced Imaging Considerations

• Cardiovascular magnetic resonance can identify minimal or absent fibrosis in HCM patients with preserved systolic function, or extensive fibrosis in restrictive/infiltrative disease 2, 3
• Cardiac MRI helps differentiate constrictive pericarditis from restrictive cardiomyopathy when echocardiography is equivocal 4
• Endomyocardial biopsy has limited routine utility but may be diagnostic in suspected infiltrative diseases (amyloidosis, sarcoidosis, hemochromatosis) when clinical suspicion is high 1

Genetic and Familial Screening

• Up to 30% of dilated cardiomyopathy has a genetic cause, and HCM has strong familial propensity 1, 6
• Family history of cardiomyopathy should trigger screening echocardiography in the patient and consideration of genetic testing 1

Common Pitfalls to Avoid

• Do not assume all LV hypertrophy in hypertensive patients is simply hypertensive heart disease—measure wall thickness precisely and assess for asymmetry 1
• Do not dismiss severe symptoms in patients with "only" diastolic dysfunction—nonobstructive HCM with preserved systolic function can require heart transplantation 2
• Recognize that some patients with HFpEF have no identifiable myocardial pathology even after thorough evaluation, but most will have detectable structural abnormalities including LV hypertrophy, atrial dilation, or myocardial scar 1
• Avoid delaying cardiomyopathy evaluation in patients with restrictive filling patterns—these patients often have accelerated progression to advanced heart failure 3

Treatment Implications of Correct Diagnosis

• HCM patients may benefit from septal reduction therapy if obstruction is present, or require specific management of diastolic dysfunction and arrhythmias 5
• Restrictive cardiomyopathy from specific causes (amyloidosis, hemochromatosis) may have disease-specific therapies (transthyretin stabilizers, iron chelation) that can alter outcomes 5
• Positive inotropic agents are contraindicated in HCM and not useful in HFpEF, whereas they may benefit systolic heart failure—making correct diagnosis essential 7
• Early recognition allows for appropriate risk stratification for sudden cardiac death in HCM and consideration for ICD placement 5