A 72-year-old woman from Mumbai with a 15-year history of atrial fibrillation (on digoxin 0.25 mg daily and warfarin) presents with worsening dyspnea, fatigue, and ankle edema over 2 months. She denies chest pain or syncope. On examination: BP 135/88 mmHg, HR 78/min (irregular), JVP 6 cm, bilateral ankle edema, quiet heart sounds, no murmurs. Chest X-ray shows mild cardiomegaly and no pulmonary edema. Echocardiography reveals LVEF 42%, dilated left atrium (LA 48 mm), normal LV wall thickness, and no significant valvular disease. NT-proBNP is 420 pg/mL. What is the most likely diagnosis?

Explanation

## Classification of Heart Failure by LVEF ```mermaid flowchart TD A[Measure LVEF]:::outcome --> B{LVEF ≥50%?}:::decision B -->|Yes| C[HFpEF<br/>Preserved EF]:::outcome B -->|No| D{LVEF 41-49%?}:::decision D -->|Yes| E[HFmrEF<br/>Mildly Reduced EF]:::outcome D -->|No| F{LVEF ≤40%?}:::decision F -->|Yes| G[HFrEF<br/>Reduced EF]:::outcome ``` ## Key Diagnostic Features in This Case | Feature | Finding | Interpretation | |---------|---------|----------------| | LVEF | 42% | Falls in HFmrEF range (41–49%) | | LV wall thickness | Normal | Rules out hypertrophic or restrictive pattern | | LA size | 48 mm (dilated) | Marker of chronic AF and elevated LA pressure | | Valvular disease | None | Excludes primary valvular etiology | | Clinical presentation | Dyspnea, edema, fatigue | Consistent with HF decompensation | | Digoxin use | Present | Suggests AF rate control, not HF-specific therapy | **High-Yield:** HFmrEF (LVEF 41–49%) is a distinct phenotype that: - Often develops in patients with chronic AF (loss of atrial contribution, RVR-induced cardiomyopathy) - Has intermediate prognosis between HFpEF and HFrEF - Requires similar GDMT as HFrEF (ACE-I/ARB, beta-blocker, MRA) [cite:ESC 2021 Heart Failure Guidelines] **Clinical Pearl:** Atrial fibrillation is a **reversible cause of cardiomyopathy**. Chronic uncontrolled AF (tachycardia-mediated cardiomyopathy) can reduce LVEF into the HFmrEF or HFrEF range. Optimal rate control and rhythm restoration (if feasible) may improve EF over time. ## Why Not the Other Options? | Option | Why Wrong | |--------|----------| | **HFpEF** | LVEF 42% is below the HFpEF threshold (≥50%); HFpEF typically presents with normal or near-normal EF and diastolic dysfunction | | **Restrictive cardiomyopathy** | Restrictive pattern shows normal or near-normal LV size with biatrial enlargement and restrictive filling; this patient has dilated LA but normal LV wall thickness and no restrictive physiology on echo | | **Dilated cardiomyopathy** | DCM is defined by LVEF ≤40% with LV dilation; this patient's EF is 42% (not ≤40%) and there is no mention of severe LV dilation, making HFmrEF the more precise classification | **Mnemonic:** **HF Classification by EF** = **HFpEF (≥50%) → HFmrEF (41–49%) → HFrEF (≤40%)**. The "m" in HFmrEF stands for "mildly reduced." ## Management Implications **Key Point:** HFmrEF management includes: 1. **Rate control** in AF (beta-blocker or non-dihydropyridine calcium channel blocker; digoxin is acceptable but less preferred) 2. **GDMT** — ACE-I/ARB, beta-blocker, MRA (similar to HFrEF) 3. **Anticoagulation** — warfarin or DOAC for stroke prevention (AF-related) 4. **Rhythm control** — consider if AF is newly diagnosed or symptomatic (may improve EF)