How does cardiac magnetic resonance imaging differentiate restrictive cardiomyopathy from hypertrophic cardiomyopathy in an adult presenting with unexplained dyspnea, heart failure symptoms, or arrhythmia?

Cardiac MRI Differentiation of Restrictive Cardiomyopathy from Hypertrophic Cardiomyopathy

Cardiac MRI with late gadolinium enhancement (LGE) is the definitive imaging modality to distinguish restrictive cardiomyopathy from hypertrophic cardiomyopathy, primarily through assessment of LV wall thickness distribution, chamber morphology, and characteristic LGE patterns—with RCM showing global subendocardial or diffuse LGE versus HCM's patchy mid-myocardial LGE in hypertrophied segments. 1, 2

Primary Morphologic Distinctions

Ventricular Wall Thickness and Distribution:

• HCM demonstrates asymmetric or focal left ventricular hypertrophy (typically ≥15 mm in adults), most commonly affecting the septum, but CMR is superior to echocardiography in detecting anterolateral wall, posterior septum, and apical hypertrophy that may be missed on echo 1, 2
• RCM shows normal or mildly increased wall thickness with symmetric distribution, distinguishing it from the focal/asymmetric pattern of HCM 3
• CMR using steady-state free precession (SSFP) cine sequences provides precise wall thickness measurements without the acoustic window limitations of echocardiography 1

Chamber Characteristics:

• RCM presents with marked biatrial enlargement (both left and right atria significantly dilated) with normal or small ventricular cavity sizes and preserved systolic function 3
• HCM typically shows normal atrial size (unless advanced disease with atrial fibrillation) with a hyperdynamic, non-dilated left ventricle 4
• RCM demonstrates restrictive filling pattern with elevated filling pressures bilaterally, while HCM shows predominantly left-sided diastolic dysfunction 3, 5

Late Gadolinium Enhancement Patterns (Critical Differentiator)

RCM-Specific LGE Patterns:

• Global subendocardial LGE is the hallmark of cardiac amyloidosis (the most common infiltrative RCM), often with diffuse or transmural extension 1, 2
• The number of LGE segments is significantly greater in cardiac amyloidosis compared to HCM, with all amyloid patients showing global endocardial pattern 6
• Abnormal myocardial and blood-pool gadolinium kinetics are highly specific for amyloidosis, with early nulling of myocardium and dark blood pool 1

HCM-Specific LGE Patterns:

• Patchy, mid-myocardial LGE predominantly in areas of hypertrophy, representing myocardial disarray and fibrosis 1, 2
• LGE is present in 46-73% of HCM patients and is most prevalent in hypertrophied segments, but may be absent in young patients or those with mild disease 1
• The distribution is typically focal and segmental rather than the global pattern seen in infiltrative RCM 6, 4

Advanced Tissue Characterization

T1 Mapping and Extracellular Volume (ECV):

• Native T1 and ECV values are markedly elevated in cardiac amyloidosis (>1100 ms for native T1), more sensitive than LGE alone and reliably distinguish amyloidosis from HCM 1, 2
• HCM shows elevated T1 in hypertrophied segments but not the global elevation seen in infiltrative disease 1
• Post-contrast T1 difference between subepicardium and subendocardium >23 ms predicts mortality in amyloidosis 1

T2 Mapping:

• Low T2 values in cardiac amyloidosis help distinguish it from other causes of LVH 1
• Elevated T2 in HCM may indicate acute inflammation or edema, particularly in acute presentations 1

Specific Infiltrative Disease Patterns

Anderson-Fabry Disease (Restrictive Phenocopy):

• Characterized by reduced non-contrast T1 signal (opposite of amyloidosis) and posterolateral LGE 1
• May present with concentric LVH mimicking HCM but with distinct T1 characteristics 2

Cardiac Sarcoidosis (Can Mimic Either):

• Patchy, mid-myocardial or subepicardial LGE, most commonly in basal septal and lateral walls 1
• High T2 signal in acute stages indicating edema, distinguishing it from chronic fibrosis 1
• FDG-PET/CT shows high uptake with 89% sensitivity and 78% specificity for diagnosis 1

Functional Assessment

Systolic Function:

• RCM maintains preserved ejection fraction until end-stage disease 3
• HCM shows hyperdynamic systolic function with ejection fraction typically >65%, though end-stage HCM may develop systolic dysfunction 6, 4
• Significant differences exist in end-diastolic and end-systolic volume indices between amyloidosis, HCM, and hypertensive heart disease 6

Diastolic Function:

• Both conditions show diastolic dysfunction, but RCM demonstrates restrictive filling pattern bilaterally (affecting both ventricles) 3, 5
• HCM shows predominantly left-sided diastolic dysfunction with preserved right ventricular function until advanced stages 5

Associated Findings

Pericardial and Pleural Effusions:

• Pericardial effusion is significantly more common in cardiac amyloidosis than in HCM or hypertensive heart disease 6
• Pleural effusions may accompany advanced RCM due to systemic congestion 3

Valvular Involvement:

• Cardiac amyloidosis shows thickening of atria, interatrial septum, and valves on CMR 1
• HCM may show systolic anterior motion of the mitral valve and mitral regurgitation, but valve leaflets themselves are not thickened 1

Diagnostic Algorithm

Step 1: Assess Wall Thickness and Distribution

• Focal/asymmetric hypertrophy (especially septal) → favor HCM 1, 2
• Normal or symmetric mild hypertrophy → favor RCM 3

Step 2: Evaluate Chamber Morphology

• Marked biatrial enlargement with normal ventricles → RCM 3
• Normal atrial size with hyperdynamic LV → HCM 4

Step 3: Analyze LGE Pattern

• Global subendocardial/diffuse LGE → cardiac amyloidosis (RCM) 1, 2, 6
• Patchy mid-myocardial LGE in hypertrophied segments → HCM 1, 2
• Posterolateral LGE with low T1 → Fabry disease 1, 2

Step 4: Perform T1/T2 Mapping

• Markedly elevated native T1 and ECV → amyloidosis 1, 2
• Reduced T1 → Fabry disease 1
• Elevated T1 only in hypertrophied segments → HCM 1

Step 5: Consider Additional Testing if Uncertain

• Nuclear imaging (Tc-PYP/DPD) for TTR amyloidosis confirmation 1
• FDG-PET for suspected cardiac sarcoidosis 1
• Endomyocardial biopsy if noninvasive studies remain inconclusive 3

Critical Pitfalls to Avoid

Technical Errors:

• Over-estimation of wall thickness from oblique sections, particularly at the LV apex, or inclusion of moderator band/false tendons 1
• Use spoiled gradient echo sequences instead of SSFP cine sequences, leading to inaccurate measurements 1
• Inadequate gadolinium dose or timing affecting LGE detection 2

Diagnostic Pitfalls:

• End-stage HCM can mimic RCM with wall thinning, cavity dilation, and systolic dysfunction—look for history of prior hypertrophy and LGE pattern 6, 5
• HCM with restrictive physiology exists as a phenotypic variant, representing overlap between the two conditions in families with sarcomeric mutations 5
• Absence of LGE does not exclude HCM, particularly in young patients or those with mild disease 1
• Hypertensive heart disease can mimic both conditions—clinical context and LGE pattern are critical 6

Contraindications and Limitations:

• CMR may not be feasible with pacemakers/ICDs (though newer MRI-conditional devices exist), severe renal insufficiency (gadolinium contraindicated), claustrophobia, or extreme body habitus 1
• Interpretation requires experienced teams in cardiac imaging and cardiomyopathy evaluation (Class I recommendation) 1, 2

Prognostic Implications

HCM:

• Extensive LGE (≥15% of LV mass) associated with 2-fold increased risk of sudden cardiac death and cardiovascular mortality 1, 2
• LGE correlates with non-sustained ventricular tachycardia on Holter monitoring 1

RCM:

• Transmural LGE in amyloidosis predicts adverse events including death 1
• Post-contrast T1 difference >23 ms between subepicardium and subendocardium predicts mortality with high accuracy 1
• Prognosis generally poor despite optimal medical treatment, unlike HCM which has variable outcomes 3