Recognising and Monitoring Cardiac AL Amyloidosis: ESC 2026 Update

AL amyloidosis is a plasma cell dyscrasia characterised by the extracellular deposition of misfolded immunoglobulin light chains as insoluble amyloid fibrils in various organs. Cardiac involvement is the leading cause of mortality in AL amyloidosis, affecting approximately 50% of patients at diagnosis.¹ The prognosis for patients with cardiac AL amyloidosis is poor, with a median survival of less than 6 months for those with advanced cardiac disease if left untreated.² Early and accurate diagnosis of cardiac involvement is therefore essential to guide appropriate treatment strategies and improve patient outcomes.

The pathophysiology of cardiac AL amyloidosis involves the direct toxicity of amyloid fibrils to cardiomyocytes, leading to progressive ventricular wall thickening, restrictive cardiomyopathy, and diastolic dysfunction.³ This can manifest clinically as heart failure with preserved ejection fraction (HFpEF), arrhythmias, and conduction abnormalities.⁴ The challenge in diagnosis stems from the non-specific nature of early symptoms, which can include fatigue, dyspnea on exertion, and peripheral edema, often mimicking more common cardiac conditions.⁵

Recognising and Monitoring Cardiac Involvement

The European Society of Cardiology (ESC) guidelines and expert consensus statements emphasise a multi-modality approach for the diagnosis and monitoring of cardiac AL amyloidosis.⁶ Initial screening for cardiac involvement should be performed in all patients with newly diagnosed AL amyloidosis. This typically includes a 12-lead electrocardiogram (ECG), transthoracic echocardiography, and measurement of cardiac biomarkers, specifically N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) or I (hs-cTnI).⁷

ECG findings in cardiac AL amyloidosis can be variable but often include low voltage in the limb leads, pseudo-infarct patterns (Q waves in anterior or inferior leads), and conduction disturbances such as atrioventricular block.⁸ However, ECG changes are not universally present and lack specificity. Transthoracic echocardiography is a cornerstone of diagnosis, revealing characteristic features such as increased left ventricular (LV) wall thickness (often >12 mm in the absence of hypertension or valvular disease), a granular sparkling appearance of the myocardium, bi-atrial enlargement, and restrictive filling patterns.⁹ Speckle-tracking echocardiography, particularly global longitudinal strain (GLS), has emerged as a sensitive tool for detecting subclinical myocardial dysfunction, often abnormal even when conventional ejection fraction is preserved. A reduced GLS (e.g., less negative than -15%) is highly suggestive of amyloid infiltration.¹⁰

Cardiac biomarkers are critical for risk stratification and monitoring disease progression. Elevated NT-proBNP (e.g., >1800 ng/L) reflects increased ventricular wall stress, while elevated hs-cTnT (e.g., >0.025 μg/L) indicates myocardial damage.¹¹ The Mayo Clinic staging system, which incorporates NT-proBNP, hs-cTnT, and difference between involved and uninvolved free light chains (dFLC), is widely used for risk stratification and prognostication.¹² Patients with stage III cardiac involvement (e.g., NT-proBNP >1800 ng/L and hs-cTnT >0.025 μg/L) have a significantly worse prognosis compared to those with earlier stages.¹²

Further diagnostic confirmation often requires cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE). CMR provides detailed anatomical and functional information and can detect diffuse myocardial LGE, particularly in a global subendocardial pattern, which is highly characteristic of cardiac amyloidosis.¹³ T1 mapping and extracellular volume (ECV) quantification by CMR can also quantify the amyloid burden.¹⁴ In cases where non-AL amyloidosis is suspected, technetium-99m pyrophosphate (PYP) scintigraphy can differentiate ATTR amyloidosis from AL amyloidosis, as PYP avidly binds to ATTR fibrils but not typically to AL fibrils.¹⁵ Endomyocardial biopsy remains the gold standard for definitive diagnosis, allowing for histological confirmation of amyloid deposits and typing of the amyloid protein.¹⁶ However, its invasiveness limits its routine use, and it is often reserved for atypical presentations or when non-invasive tests are inconclusive.

Monitoring of cardiac involvement involves serial assessment of symptoms, physical examination, ECG, echocardiography, and cardiac biomarkers. Changes in NT-proBNP and hs-cTnT levels are particularly useful for tracking response to treatment and identifying disease progression.¹⁷ A reduction in NT-proBNP by >30% from baseline is often considered a marker of cardiac response to therapy.¹⁷ Regular follow-up with a multidisciplinary team, including cardiologists, haematologists, and nephrologists, is essential for optimal management.