Cardiac amyloidosis and aortic stenosis: a state-of-the-art review

Abstract

Cardiac amyloidosis is caused by the extracellular deposition of amyloid fibrils in the heart, involving not only the myocardium but also any cardiovascular structure. Indeed, this progressive infiltrative disease also involves the cardiac valves and, specifically, shows a high prevalence with aortic stenosis. Misfolded protein infiltration in the aortic valve leads to tissue damage resulting in the onset or worsening of valve stenosis. Transthyretin cardiac amyloidosis and aortic stenosis coexist in patients > 65 years in about 4-16% of cases, especially in those undergoing transcatheter aortic valve replacement. Diagnostic workup for cardiac amyloidosis in patients with aortic stenosis is based on a multi-parametric approach considering clinical assessment, electrocardiogram, haematologic tests, basic and advanced echocardiography, cardiac magnetic resonance, and technetium labelled cardiac scintigraphy like technetium-99 m (^99mTc)-pyrophosphate, ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, and ^99mTc-hydroxymethylene diphosphonate. However, a biopsy is the traditional gold standard for diagnosis. The prognosis of patients with coexisting cardiac amyloidosis and aortic stenosis is still under evaluation. The combination of these two pathologies worsens the prognosis. Regarding treatment, mortality is reduced in patients with cardiac amyloidosis and severe aortic stenosis after undergoing transcatheter aortic valve replacement. Further studies are needed to confirm these findings and to understand whether the diagnosis of cardiac amyloidosis could affect therapeutic strategies. The aim of this review is to critically expose the current state-of-art regarding the association of cardiac amyloidosis with aortic stenosis, from pathophysiology to treatment.

Keywords: Aortic stenosis; Cardiac amyloidosis; Cardiomyopathy; Diagnosis.

Graphical Abstract

Cardiac amyloidosis and aortic stenosis: diagnostic imaging, clinical presentation, and management criteria. ATTR-CA, transthyretin cardiac amyloidosis; AL-CA, amyloid light chain–cardiac amyloidosis; AV, aortic valve; CMR, cardiac magnetic resonance; ECG, electrocardiogram; TTE, transthoracic echocardiogram.

Figure 1

Pathophysiology of amyloidosis and its effects on the development and progression of aortic stenosis. AA amyloidosis, secondary amyloidosis; AL amyloidosis, amyloid light chain amyloidosis; ATTR amyloidosis, transthyretin amyloidosis; IL-1, interleukin-1; IL-6, interleukin-6; ROS, reactive oxygen species; SAA, serum amyloid A protein; TTR, ttransthyretin.

Figure 2

Clinical ‘red flags’ suspecting of cardiac amyloidosis in aortic stenosis. LGE, late gadolinium enhancement.

Figure 3

Diagnostic algorithm of amyloidosis in patients with confirmed aortic stenosis. ATTR, transthyretin amyloidosis; CMR, cardiac magnetic resonance imaging; DPD, 3,3-diphosphono-1,2-propanodicarboxilic acid; ECG, electrocardiography; HMDP, hydroxymethylene diphosphonate; PYP, pyrophosphonate; TTE, transthoracic echocardiography.

Figure 4

Current medical/surgical management of cardiac amyloidosis and aortic stenosis with relevant clinical trials ongoing for pharmacotherapies. ACEi, angiotensin convertase enzyme inhibitors; AL-CA, immunoglobulin light chain amyloidosis; ARBs, angiotensin receptor blockers; ATTR-CA, transthyretin cardiac amyloidosis; ATTR-h, hereditary transthyretin amyloidosis; PCSK-9i, proprotein convertase subtilisin/kexin type 9 serine protease inhibitors; wtTTR-CA, wild-type transthyretin cardiac amyloidosis.