In a patient with mildly reduced left ventricular ejection fraction (~48%), mildly reduced right ventricular ejection fraction (~45%), severe left atrial enlargement, and cardiac MRI showing non‑ischemic mid‑wall late gadolinium enhancement in the basal inferior‑lateral wall and fibrosis at the right‑ventricular septal insertion, what are the most likely non‑ischemic causes and what is the next step to identify the underlying etiology?

Likely Causes of Non-Ischemic Cardiomyopathy Based on MRI Findings

The MRI pattern of mild patchy mid-wall late gadolinium enhancement in the basal inferior-lateral wall with RV insertion site fibrosis most strongly suggests either idiopathic dilated cardiomyopathy or early cardiac sarcoidosis, with sarcoidosis being the most critical diagnosis to exclude given its treatment implications. 1

Primary Differential Diagnoses

Cardiac Sarcoidosis (Most Important to Exclude)

• Cardiac sarcoidosis demonstrates mid-myocardial or subepicardial LGE most commonly in the basal septal and lateral walls of the LV, matching your patient's inferior-lateral wall involvement 1
• The pattern of patchy mid-myocardial enhancement at the basal level is characteristic of sarcoidosis, with MRI sensitivity of 75-100% and specificity of 75-77% 1
• Severe left atrial dilatation can occur with sarcoidosis due to diastolic dysfunction from infiltrative disease 1
• This diagnosis is critical because patients with lower LGE burden at initiation of steroid therapy show good response, making early detection vital for mortality reduction 1

Idiopathic Dilated Cardiomyopathy

• Linear or patchy mid-myocardial LGE primarily at the base and mid septum occurs in 28% of idiopathic DCM patients with non-obstructed coronary arteries 1
• RV insertion point enhancement is seen in dilated cardiomyopathy and represents interstitial fibrosis related to ventricular remodeling 2
• The biventricular dysfunction (LV EF 48%, RV EF 45%) with severe LA enlargement fits the DCM phenotype 1

Scleroderma/Systemic Sclerosis

• Linear mid-myocardial LGE is seen in 66% of scleroderma patients, either in the ventricular septum or LV free wall at basal and mid levels 1
• Patchy RV insertion enhancement occurs in 17% of scleroderma patients 1
• Evaluate for Raynaud's phenomenon, skin changes, dysphagia, or pulmonary fibrosis 1

Genetic Cardiomyopathies (Lamin A/C)

• Mid-myocardial fibrosis of the basal interventricular septum is characteristic of lamin A/C cardiomyopathy 3
• This pattern can form the substrate for diastolic dysfunction and severe LA enlargement 3
• Consider if there is family history of sudden cardiac death, conduction disease, or early-onset cardiomyopathy

Next Diagnostic Steps (Algorithmic Approach)

Immediate Priority: Exclude Cardiac Sarcoidosis

Step 1: FDG-PET/CT of the Heart

• FDG-PET/CT has 89% sensitivity, 78% specificity, and 93% area under the curve for diagnosis of cardiac sarcoidosis 1
• Requires strict dietary preparation (high-fat, low-carbohydrate diet for 24-48 hours before scan) to suppress physiologic myocardial glucose uptake 1
• FDG activity can be quantified to assess disease activity and evaluate prognosis 1
• Nearly 50% of patients with unexplained cardiomyopathy and arrhythmia demonstrate focal inflammation on FDG-PET/CT, indicating inflammatory cardiomyopathy 1

Step 2: Systemic Sarcoidosis Evaluation

• Chest CT to evaluate for mediastinal lymphadenopathy and pulmonary involvement 1
• Serum ACE level and lysozyme (elevated in 60% of active sarcoidosis)
• Complete ophthalmologic examination for uveitis
• Pulmonary function tests if chest imaging abnormal

Step 3: Advanced Cardiac MRI Sequences

• Native T1 mapping and T2 mapping provide higher discriminatory accuracy than traditional criteria for sarcoidosis 1
• High native T1 and T2 values indicate active inflammation in sarcoidosis 1
• T2-weighted imaging to assess for myocardial edema (acute inflammation) 1
• Extracellular volume (ECV) quantification—elevated ECV indicates diffuse fibrosis 1

Secondary Evaluation: Systemic Diseases

Autoimmune/Connective Tissue Disease Screening

• Antinuclear antibody (ANA), anti-Scl-70, anti-centromere antibodies for scleroderma 1
• Rheumatoid factor, anti-CCP if inflammatory arthritis suspected
• Creatine kinase, aldolase for inflammatory myopathy
• Specifically ask about Raynaud's phenomenon duration, as LGE severity correlates with longer Raynaud's disease duration in scleroderma 1

Genetic Testing

• Consider genetic panel for cardiomyopathy genes including LMNA, desmosomal genes (PKP2, DSP, DSG2, DSC2, JUP), and titin (TTN) 3
• Particularly important if family history of sudden death, conduction disease, or young-onset cardiomyopathy
• LMNA mutations show mid-myocardial fibrosis of basal interventricular septum identical to your patient's pattern 3

Tertiary Considerations

Endomyocardial Biopsy

• MRI can guide endomyocardial biopsy to areas of active inflammation if required 1
• Consider if FDG-PET positive for inflammation or if diagnosis remains unclear after non-invasive testing
• Highest yield when targeting areas of T2 hyperintensity (edema) on MRI 1

Critical Prognostic Implications

RV Insertion Point Fibrosis Significance

• RV insertion site LGE in isolation (without additional LV LGE) is associated with intermediate risk and does NOT significantly increase risk of adverse cardiac events 4
• However, when combined with LV mid-wall LGE (as in your patient), it indicates more advanced disease with 2.6-fold increased risk of heart failure admission or death 2
• RV insertion fibrosis represents pre-requisite for incremental development of mid-wall striae fibrosis, a more advanced phenotype 2

Mid-Wall LGE Prognostic Value

• Mid-wall LGE in idiopathic DCM is a strong independent predictor of all-cause mortality, cardiovascular death/transplantation, and sudden cardiac death 1
• Native T1 value, ECV value, presence and extent of LGE, and EF all correlate with adverse prognosis 1
• Using LGE findings, 19% of additional patients gained indication for ICD, and 11% avoided previously planned ICD compared to standard of care 1

Common Pitfalls to Avoid

• Do not dismiss RV insertion point enhancement as "non-specific"—when combined with LV LGE, it indicates biventricular remodeling and intermediate-to-high risk 2, 4
• Do not delay FDG-PET if sarcoidosis is suspected—early detection with lower LGE burden predicts better response to steroids 1
• Do not assume all mid-wall LGE is idiopathic DCM without excluding treatable causes like sarcoidosis and scleroderma 1
• Ensure proper patient preparation for FDG-PET (high-fat, low-carb diet) to avoid false negatives from physiologic myocardial uptake 1
• Do not overlook family history—genetic cardiomyopathies like LMNA mutations show identical basal mid-wall fibrosis patterns 3