Advanced Cardiac MRI Identifies Early Signs of Transthyretin Amyloidosis

Advanced cardiac magnetic resonance (CMR) imaging has potential to detect early-stage transthyretin cardiac amyloidosis (ATTR-CA), offering clinicians a powerful tool to distinguish this progressive condition from similar heart diseases before it advances, according to a study in European Heart Journal Imaging Methods and Practice.¹

The researchers note that these findings could have important implications for clinical practice. By identifying characteristic imaging features of early disease, CMR may enable clinicians to diagnose ATTR-CA sooner, potentially allowing earlier initiation of disease-m

odifying therapies. However, they cautioned that their study was conducted at a single center with a relatively small sample size.

ATTR-CA is a form of amyloidosis caused by the accumulation of misfolded transthyretin proteins in the heart, leading to stiffening of the myocardium and eventual heart failure (HF). The condition is increasingly recognized, particularly among older adults. However, despite growing awareness, diagnosing ATTR-CA at an early stage remains challenging. Traditional imaging findings often reflect more advanced disease, while early or “low-burden” cases may resemble other conditions such as hypertensive heart disease (HHD) or mild hypertrophic cardiomyopathy (HCM), which can delay diagnosis and treatment.

In this new study, researchers analyzed 83 patients with confirmed ATTR-CA who underwent contrast-enhanced CMR. Patients were categorized by disease burden using myocardial extracellular volume (ECV), a key imaging biomarker that reflects the extent of amyloid infiltration in the heart. There were 22 patients with ECV ≤43% who were classified as having low disease burden, representing earlier-stage disease.

The findings revealed that even at low levels of disease burden, ATTR-CA produces distinct imaging patterns that can be detected with CMR. Unlike more advanced disease, which often shows diffuse cardiac involvement, early-stage ATTR-CA demonstrated a more localized pattern of infiltration.

Patients with low-burden disease exhibited late gadolinium enhancement primarily in the basal segments of the left ventricle, especially in the inferolateral and inferior regions, while the mid and apical regions were relatively spared. This “basal-predominant” pattern may serve as an early imaging signature of the disease, explained the researchers.

Quantitative tissue characterization further reinforced these findings. Measures such as global ECV, native T1 mapping, and the extent of LGE increased progressively with disease burden, reflecting greater amyloid deposition over time. However, even in low-burden cases, these parameters were significantly elevated compared with patients with HCM or HHD, providing a means to distinguish ATTR-CA from similar conditions.

Diagnostic performance analyses showed that CMR tissue characterization metrics were highly accurate in differentiating low-burden ATTR-CA. Global LGE and ECV demonstrated near-perfect discrimination, with area under the curve (AUC) values approaching 0.99 and 0.97, respectively, substantially outperforming traditional strain-based measures. These findings suggest that tissue characterization, rather than functional measures alone, may be key to identifying early disease.

Clinically, patients with low-burden ATTR-CA also differed from those with more advanced disease. They exhibited milder structural changes, including normal or only slightly increased left ventricular wall thickness, and relatively preserved cardiac function. However, subtle abnormalities in myocardial strain and biomarker levels indicated underlying disease activity.

Importantly, prognosis appeared more favorable in this group. Patients with low ECV burden had better survival outcomes compared with those with higher disease burden, emphasizing the value of early detection.

“It is not clear whether low-burden ATTR-CA represents an early disease stage or patients with slower disease progression,” noted the researchers. “The latter possibility highlights the potential role of innate amyloidosis homeostatic mechanisms beyond disease-modifying therapies. For example, the impact of estrogen in terms of reducing the detrimental effects of amyloid fibrils on cardiac function has been previously described, suggesting a potential protective effect of this hormone.”

The study also provided insight into how ATTR-CA differs from other causes of left ventricular hypertrophy. While HCM typically affects the anteroseptal region and HHD shows minimal fibrosis, ATTR-CA preferentially involves the basal inferolateral segments and is associated with significantly higher levels of myocardial tissue abnormalities.

Reference

Mengesha B, Prabhakar S, Small GR, et al. Low burden transthyretin cardiac amyloidosis on cardiac magnetic resonance: comprehensive phenotyping and distinction from hypertrophic phenocopies. Eur Heart J Imaging Methods Pract. 2026;4(1):qyag038. doi:10.1093/ehjimp/qyag038