Evolving trends in epidemiology and natural history of cardiac amyloidosis: 30-year experience from a tertiary referral center for cardiomyopathies

Abstract

ObjectiveNatural history of cardiac amyloidosis (CA) is poorly understood. We aimed to examine the changing mortality of different types of CA over a 30-year period.Patients and methodsConsecutive patients included in the “Trieste CA Registry” from January 1, 1990 through December 31, 2021 were divided into a historical cohort (diagnosed before 2016) and a contemporary cohort (diagnosed after 2016). Light chain (AL), transthyretin (ATTR) and other forms of CA were defined according to international recommendations. The primary and secondary outcome measures were all-cause mortality and cardiac death, respectively.ResultsWe enrolled 182 patients: 47.3% AL-CA, 44.5% ATTR-CA, 8.2% other etiologies. The number of patients diagnosed with AL and ATTR-CA progressively increased over time, mostly ATTR-CA patients (from 21% before 2016 to 67% after 2016) diagnosed non-invasively. The more consistent increase in event-rate was observed in the long-term (after 50 months) in ATTR-CA compared to the early increase in mortality in AL-CA. In the contemporary cohort, during a median follow up of 16 [4–30] months, ATTR-CA was associated with improved overall and cardiac survival compared to AL-CA. At multivariable analysis, ATTR-CA (HR 0.42, p = 0.03), eGFR (HR 0.98, p = 0.033) and ACE-inhibitor therapy (HR 0.24, p < 0.001) predicted overall survival in the contemporary cohort.ConclusionIncidence and prevalence rates of ATTR-CA and, to a less extent, of AL-CA have been increasing over time, with significant improvements in 2-year survival of ATTR-CA patients from the contemporary cohort. Reaching an early diagnosis and starting disease-modifying treatments will improve long-term survival in CA.

Recent advances in the diagnostic methods and therapeutic strategies of transthyretin cardiac amyloidosis

“…The second phase of the study showed that the prevalence of cardiac amyloidosis was 29% in consecutive adults with echocardiographic findings suggestive of cardiac amyloidosis and LVEF ≥ 50%, while combined echocardiographic red flags usually present good diagnostic accuracy[ 5 ]. Similarly, Porcari et al [ 6 ] examined mortality rates between ATTR and AL cardiac amyloidosis over a 30-year period in Italy and found that incidence and prevalence rates of ATTR and AL cardiac amyloidosis are much higher the last decade compared to the previous ones, but the 2-year survival of ATTR amyloidosis has improved over the years compared to AL cardiac amyloidosis.…”

World Heart Federation Consensus on Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM)

“…One of the primary challenges is to achieve an early diagnosis of amyloidosis. Despite significant advancements in the understanding of ATTR-CM, including epidemiology, diagnosis, and treatment [21,26,199,283,284] there remains a substantial number of undiagnosed patients who have been observed by different specialists for several years before receiving the correct diagnosis [285][286][287]. This delay in diagnosis not only hampers timely treatment but also has profound emotional effects on patients [285][286][287].…”

Recent Progress in the Development and Clinical Application of New Drugs for Transthyretin Cardiac Amyloidosis

“…Currently, patients with ATTR-CA show a more favorable cardiovascular prognosis than patients with AL-CA, which is associated with therapeutic agents that have been developed in recent years. 22…”

“…Currently, patients with ATTR-CA show a more favorable cardiovascular prognosis than patients with AL-CA, which is associated with therapeutic agents that have been developed in recent years. 22 The contemporary approach to the diagnosis and treatment of ATTR-CA involves a sequential process. Clinicians must begin by assessing the likelihood of ATTR-CA, relying on clinical features associated with the cardiac amyloidosis phenotype.…”