Beyond Late Gadolinium Enhancement: Multimodality Imaging in the Diagnosis of Cardiac Amyloidosis

Description of Clinical Presentation: A 71-year-old man with a past medical history of type 2 diabetes mellitus, hypertension, dyslipidemia, obesity, and progressive weight loss of 25 kg over 5 months presented with new-onset exertional dyspnea, marked fatigue, and recurrent presyncope. His symptoms had gradually worsened despite medical therapy, and he had developed signs of orthostatic intolerance and functional limitation corresponding to NYHA class III. On physical examination, he was hypotensive (88/66 mmHg) with tachycardia (105 bpm). Laboratory evaluation showed markedly elevated NT-proBNP (8,700 pg/mL), mild anemia, and abnormal serum free light chain profile with increased lambda concentration (58.46 mg/L) and abnormal κ/λ ratio (0.66). The clinical picture was consistent with suspected infiltrative cardiomyopathy.

Diagnostic Techniques and Their Most Important Findings: Transthoracic echocardiography revealed concentric left ventricular hypertrophy, severe grade III diastolic dysfunction, global hypokinesia, and reduced 3D LVEF (41%). Right ventricular systolic pressure was elevated at 58 mmHg. Cardiac magnetic resonance (CMR) was performed using cine imaging, late gadolinium enhancement (LGE), and parametric mapping. Imaging demonstrated diffuse subendocardial LGE of the left ventricle, with additional enhancement of the left atrial wall and tricuspid valve. Multiparametric mapping revealed significantly increased native T1 values ( >1050 ms) and elevated extracellular volume (ECV >40%), confirming diffuse myocardial infiltration. These findings extended beyond the conventional LGE pattern, offering quantitative evidence of amyloid infiltration. Nuclear scintigraphy with 99mTc-DPD showed no myocardial uptake, ruling out transthyretin amyloidosis. Bone marrow biopsy demonstrated 20% interstitial infiltration by lambda light chain–restricted plasma cells (CD138+), consistent with AL amyloidosis. The integration of multimodality imaging with hematologic studies established the diagnosis of systemic AL cardiac amyloidosis without requiring endomyocardial biopsy.

Learning Points from this Case:

• Multiparametric CMR mapping, including native T1 and ECV quantification, provides objective and reproducible evidence of diffuse myocardial infiltration, enhancing diagnostic accuracy beyond conventional late gadolinium enhancement.


• The combined use of CMR, echocardiography, nuclear scintigraphy, and hematologic testing allows accurate differentiation between AL and ATTR subtypes, enabling non-invasive diagnosis in many patients.


• Early recognition of cardiac amyloidosis through advanced imaging facilitates timely access to disease-modifying therapies and optimized heart failure management, which may improve prognosis and quality of life.


• Multiparametric mapping holds promise not only for diagnosis but also for disease staging, monitoring treatment response, and guiding therapeutic decision-making in cardiac amyloidosis.

Diagnostic Contribution of Multimodality Imaging in Cardiac Amyloidosis

Modality	Main Findings	Diagnostic Contribution
Echocardiography	Concentric LV hypertrophy, severe diastolic dysfunction, LVEF 41%	Non-specific evidence of infiltrative cardiomyopathy
CMR – Late Gadolinium Enhancement	Diffuse subendocardial enhancement of LV, atrial wall, and tricuspid valve	Classic marker of amyloid infiltration, but qualitative only
CMR – Native T1 Mapping	Elevated T1 >1050 ms	Quantitative evidence of diffuse myocardial infiltration
CMR – Extracellular Volume	ECV >40%	Burden quantification, highly supportive of cardiac amyloidosis
99mTc-DPD Scintigraphy	Negative myocardial uptake	Ruled out ATTR subtype
Bone Marrow Biopsy	Lambda light chain–restricted plasma cell neoplasm	Confirmed systemic AL amyloidosis