Serial Native T1 Mapping to Monitor Cardiac Response to Treatment in Light-Chain Amyloidosis

Abstract

A myloidosis is a condition in which misfolded proteins form insoluble deposits in the extracellular space of various tissues and organs, leading to interstitial expansion and disruption of structure and function. Light-chain (AL) amyloidosis is caused by an underlying plasma cell dyscrasia; cardiac involvement is common, is present in ≈50% of patients at presentation, and is a principal driver of morbidity and mortality.1 In practice, there has been reliance on ECG and echocardiographic features, as well as serum cardiac biomarkers, such as pro-brain natriuretic peptide and troponin T concentrations, for prognostic purposes and correlation to clinical response to treatment. However, these parameters can be of limited use because of concomitant etiologies for left ventricular (LV) hypertrophy and coexisting renal impairment. T1 relaxation time for hydrogen magnetization in the myocardium, an intrinsic characteristic of tissue, has been studied in a variety of pathologies with diffuse processes, including amyloidosis. Native, also known as noncontrast or precontrast, T1 mapping can be performed without the use of gadolinium-based contrast in patients with significantly reduced glomerular filtration rate. The technique of T1 mapping with cardiovascular magnetic resonance (CMR), in which T1 relaxation times for all pixels in the acquired image of the heart are measured, has been used for purposes of tissue characterization in regards to the diagnosis of cardiac involvement 2 and prognosis in AL amyloidosis 3 at single time point evaluations. Here we present a case using serial CMR native T1 mapping to assess treatment response of AL amyloidosis in a patient with renal failure.A 60-year-old Caucasian woman with a past medical history of hyperlipidemia, chronic obstructive pulmonary disease, and chronic kidney disease experienced progressive symptoms of fatigue over the course of a year with ongoing declining renal function. As part of the work-up, a renal biopsy demonstrated AL amyloidosis, and a bone marrow biopsy demonstrated the presence of a plasma cell neoplasm. In addition, she had elevated beta-2 microglobulin (20.03 mg/L; reference range ≤2.64), immunoglobulin kappa-free light chains (58.10 mg/dL; reference range 0.33-1.94), and kappa:lambda-free light chains ratio (24.94; reference range 0.26-1.65) values, as well as abnormal troponin T (0.17 ng/mL; reference range <0.01) and pro-brain natriuretic peptide (>70 000 pg/mL; reference range <300). The AL amyloidosis was treated with a course of cyclophosphamide, bortezomib, and dexamethasone for the first 8 months, followed by pomalidomide for maintenance therapy. She was referred for onco-cardiology evaluation and followup during chemotherapy treatment, given the cardiac findings of low-voltage ECG (Figure 1), LV hypertrophy, and diastolic dysfunction (Figure 2) on transthoracic echocardiography and abnormal cardiac biomarkers. Her ongoing renal failure with a glomerular filtration rate of <30 mL/min/m 2 led to the initiation of hemodialysis. As her renal fail...

Transthyretin Cardiac Amyloidosis: A Noninvasive Multimodality Approach to Diagnosis Using Transthoracic Echocardiography, 99m-Tc-Labeled Phosphate Bone Scanning, and Cardiac Magnetic Resonance Imaging

“… 22 Serial T1 mapping can therefore be used in amyloidosis to monitor both disease progression and response to therapies. 23 In comparison with AL amyloidosis, TTR amyloidosis usually demonstrates lower native T1 values consistent with lower extracellular volume burden of disease. 24 In this case, elevated native T1 values of 1,450 (3T normal range, 1,100-1,150) and reduced postcontrast T1 of 220 (normal < 440) suggested a moderately high burden of disease, correlating with high uptake on bone scan.…”

Multimodal Imaging and Biomarkers in Cardiac Amyloidosis

“…In ATTR-CA patients, the recommended follow-up scheme involved 6-month visits with ECG and complete blood tests (including NT-proBNP and troponin) in addition to yearly echocardiography and 24 h Holter monitoring [4]. Some studies have reported the role of CMR in monitoring the treatment outcomes of patients [70,71]. Additional research is required regarding the choice of imaging modalities that are appropriate for tracing therapy-related changes.…”

State of the Art: Quantitative Cardiac MRI in Cardiac Amyloidosis

“…While treatments improve the clinical condition of patients with CA, the reduction in native T1 and ECV might represent the amyloid burden abatement, which provides compelling evidence of cardiac amyloid regression. [64][65][66][67] Recent therapeutic developments of CA have been associated with improved outcomes. The evaluation of patient responses would be essential for optimal individualized treatment strategy, closely meshed monitoring is imperative.…”