Decompensated Heart Failure as the First Sign of Multiple Myeloma

A 62-year-old man with a history of hypertension came to the emergency department complaining of five days of progressive bilateral lower extremity edema — and nothing else. No chest pain, no shortness of breath, no orthopnea, no change in exercise tolerance, no bone pain or fatigue. Vital signs were normal. His lungs were clear. The exam was essentially unremarkable except for bilateral, symmetric, non-tender pitting edema to the mid-shins.

The labs told a more complicated story. BNP was 2,110 pg/mL and troponin I was 2.11 ng/mL — markedly elevated for a patient who denied any cardiac symptoms. Additional findings included macrocytosis (MCV 114.4 fL), elevated total protein (8.3 g/dL) with a protein gap of 4.9, and a creatinine of 1.2 mg/dL. Serum protein electrophoresis showed an M-spike of 2.2 with immunofixation confirming an IgG lambda monoclonal band. Urine protein electrophoresis also showed a monoclonal peak.

An ECG showed normal sinus rhythm, low voltage in the limb leads, and signs of left atrial enlargement. The chest X-ray was consistent with vascular congestion. The initial clinical impression was ADHF secondary to NSTEMI, and the patient underwent urgent cardiac catheterization — which revealed non-obstructive coronary artery disease, ruling out a type I MI.

Figure 1

12-lead EKG: low voltage in limb leads and left atrial enlargement

Low-voltage QRS complexes in limb leads are seen in 25–50% of cardiac amyloidosis patients. Counterintuitively, in amyloidosis the LV wall thickens from amyloid deposition — not from electrically active myocyte hypertrophy — so ECG voltage actually decreases as wall thickness increases. This "voltage-mass dissociation" on ECG is a classic clue to amyloid infiltration and should raise immediate suspicion when echocardiography shows hypertrophy without the expected voltage correlation.

Figure 2

Chest X-ray demonstrating right-sided pleural effusion

Arrow indicates the right-sided pleural effusion — a manifestation of elevated filling pressures from the restrictive cardiomyopathy. Transudative pleural effusion in cardiac amyloidosis typically reflects biventricular diastolic dysfunction from amyloid deposition in the extracellular myocardial space, causing non-compliant, thickened ventricles despite normal or mildly reduced systolic function at presentation.

A transthoracic echocardiogram (TTE) showed a reduced LVEF of 40%, apical sparing of global longitudinal strain (GLS), and mild wall thickening — raising immediate concern for cardiac amyloidosis. The patient was initiated on heart failure medications and discharged with close hematology and cardiology follow-up, but was lost to outpatient care.

Three months later he returned — this time with progressive shortness of breath, worse than the first presentation. His BNP had risen to 2,863 pg/mL, troponin I remained elevated, and creatinine had worsened to 1.8 mg/dL. A repeat TTE showed LVEF 35% with severe diffuse hypokinesis, a mildly abnormal myocardial specular pattern, and characteristic apical sparing of GLS.

Figure 3

Apical four-chamber view: left ventricular hypertrophy and biatrial enlargement

Red arrow indicates LV hypertrophy; white arrows point to biatrial enlargement. This pattern — biventricular wall thickening plus biatrial dilation — is characteristic of restrictive cardiomyopathy from cardiac amyloidosis. The "granular sparkling" appearance of the myocardium on older echo systems has been replaced by more specific imaging biomarkers, but the combination of wall thickness, filling pattern, and strain abnormalities remains diagnostically powerful.

Figure 4

Global longitudinal strain pattern demonstrating apical sparing

The "bull's-eye" or strain map pattern showing relative apical preservation of longitudinal strain is one of the most sensitive and specific echocardiographic markers of cardiac amyloidosis. Amyloid fibrils preferentially deposit in the basal and mid segments of the ventricles, sparing the apex — the proposed mechanism for this strain distribution pattern. A relative apical sparing ratio (RASR) above 1.0 has high specificity for amyloid over other causes of LV hypertrophy.

Inpatient workup proceeded: abdominal fat pad biopsy showed Congo red-positive vascular deposits consistent with amyloid. Bone marrow biopsy revealed greater than 30% monotypic plasma cells co-expressing CD56 and cytoplasmic lambda light chain — diagnostic of multiple myeloma. The patient was started on cyclophosphamide, bortezomib, and dexamethasone (CyBorD) for AL amyloidosis-associated multiple myeloma.

Discussion

This case is a masterclass in diagnostic breadth-of-field. The presenting symptom was isolated lower extremity edema with a clear lung exam — a constellation that does not reflexively trigger a hematologic workup. Yet the combination of markedly elevated troponin and BNP in a patient without dyspnea, the coronary angiogram showing non-obstructive disease in a patient who clinically looked like an NSTEMI, and the echocardiographic findings of apical sparing on GLS all pointed to the same infiltrative diagnosis. The critical early diagnostic action was the recognition that the "voltage-mass dissociation" on ECG — low voltage paired with echocardiographic wall thickening — is not just a curiosity but a cardinal sign of amyloid infiltration. In typical LV hypertrophy, wall thickness and ECG voltage scale together; in cardiac amyloidosis, the thickened wall is composed of electrically inert amyloid fibrils, so voltage paradoxically decreases as the wall grows.

The management lesson here is about system design: the patient was lost to follow-up for three months between a concerning first presentation and a return visit with clearly worsened disease. The initial diagnosis was "ADHF secondary to NSTEMI" — but the catheterization had already disproven this. A clearly documented suspicion of cardiac amyloidosis at the time of the first discharge, with an urgent hematology referral and a concrete follow-up plan, might have initiated cytotoxic therapy three months earlier. Cardiac amyloidosis from AL disease has a median survival of 6–12 months without treatment — every month of delay matters. The practical takeaway for any clinician: when echocardiography shows apical sparing of GLS, treat the interpretation as a near-emergent finding and activate the amyloid workup pathway immediately, regardless of whether the patient "looks sick."