Microvascular obstruction and association with prognosis in cardiac amyloidosis

In a retrospective cohort study, microvascular obstruction was present in 28% of the patients with cardiac amyloidosis and was associated with a more severe cardiac phenotype and an increased mortality risk.

This summary is based on the publication of Netti L, Ioannou A, Martinez-Naharro A, et al. - Microvascular obstruction in cardiac amyloidosis. Eur J Heart Fail. 2024 Oct 18 [Online ahead of print]. doi: 10.1002/ejhf.3481

Introduction and methods

Background

Cardiac amyloidosis (CA) is a progressive disease that is caused by the deposition of amyloid fibrils in the myocardial extracellular space, leading to disruption of the myocardial structure and function and capillary architecture. Cardiac magnetic resonance (CMR) imaging with multiparametric mapping has shown severe inducible myocardial ischemia in patients with CA but no significant epicardial coronary artery disease [1,2].

Aim of the study

The study aim was to characterize the prevalence of microvascular obstruction (MVO) in CA patients and examine the association between MVO and prognosis.

Methods

This was a retrospective observational cohort study of 800 CA patients who underwent CMR imaging including early gadolinium enhancement at the time of diagnosis at the National Amyloidosis Centre in London, the UK in the period 2016–2021. Of the participants, 400 had light-chain CA (AL-CA) and 400 had transthyretin-mediated CA (ATTR-CA). Exclusion criteria included coronary artery disease.

Main results

Prevalence of microvascular obstruction

• At diagnosis, 221 patients (27.6%) showed MVO on CMR imaging, of whom 124 (56.1%) had ATTR-CA and 97 (43.9%) had AL-CA (P=0.033).
• Patients with MVO had a more severe cardiac phenotype than those with no MVO as shown by higher NT-proBNP levels (3516 ng/L (1944–6247) vs. 2508 ng/L (1203–5752); P<0.001), worse global longitudinal strain (–10.5% (–12.6% to –7.9%) vs. –12.0% (–16.0% to –9.2%); P<0.001), and higher extracellular volume (56% (51%–61%) vs. 50% (45%–57%); P<0.001).
• Patients with AL-CA and MVO demonstrated higher levels of NT-proBNP (5184 ng/L (2602–9835) vs. 2725 ng/L (1291–4876); P<0.001), troponin T (86 ng/L (47–148) vs. 59 ng/L (44–78); P<0.001), and myocardial T2 (marker of myocardial edema) (53 ms (50–56) vs. 50 ms (48–52); P<0.001) than patients with ATTR-CA and MVO but lower extracellular volume (55% (50%–60%) vs. 58% (53%–61%); P=0.008) and lower indexed myocyte cell volume (48.6 g/m² (41.1–59.8) vs. 55.7 g/m² (47.5–68.4); P<0.001).

Association between microvascular obstruction and prognosis

• During a median follow up time of 51.5 months (IQR: 19–60), 381 patients died (mortality rate: 14.1 deaths per 100 person-years; 95%CI: 12.7–15.6).
• In the overall population, MVO was associated with an increased risk of death (HR: 1.28; 95%CI: 1.03–1.59; P=0.025).
• Subgroup analysis demonstrated MVO was also associated with an increased mortality risk in patients with AL-CA (HR: 1.59; 95%CI: 1.17–2.17; P=0.003) but not those with ATTR-CA (HR: 1.04; 95%CI: 0.77–1.40; P=0.814).

Conclusion

In this retrospective, single-center, observational cohort study, MVO was present in 28% of the CA patients—more commonly in participants with ATTR-CA than those with AL-CA—and was related to a more severe cardiac phenotype. Furthermore, the presence of MVO was associated with an increased mortality risk in patients with AL-CA but not those with ATTR-CA. The authors conclude this finding “reflects the intrinsic differences in disease biology between these two forms of CA, with MVO likely related to multiple myocardial processes, amyloid infiltration, edema, and myocyte death.”

Find this article online at Eur J Heart Fail.

References

1. Chacko L, Kotecha T, Ioannou A, Patel N, Martinez-Naharro A, Razvi Y, et al. Myocardial perfusion in cardiac amyloidosis. Eur J Heart Fail 2024;26:598–609. https://doi.org/10.1002/ejhf.3137
2. Ioannou A, Patel RK, Razvi Y, Porcari A, Knight D, Martinez-Naharro A, et al. Multi-imaging characterization of cardiac phenotype in different types of amyloidosis. JACC Cardiovasc Imaging 2022;16:464–477. https://doi.org/10.1016/j.jcmg.2022.07.008