Aortic Stenosis Outcomes Worsen With Cardiac Amyloidosis Also in the Picture

People with transthyretin cardiac amyloidosis (ATTR-CA) on top of aortic stenosis (AS) fared particularly poorly in a large cohort study, which researchers said calls for awareness and timely treatment.

Compared with AS alone, coexisting ATTR-CA was associated with an increased risk of mortality (HR 1.3, 95% CI 1.1-1.4) in a nationwide administrative claims database covering more than 355,000 individuals. Two-year death rates reached 16.1%, 14.8%, and 19.2% in AS-only, ATTR-CA-only, and dual diagnosis cohorts.

Similarly, diagnoses of AS and ATTR-CA together were linked to a higher heart failure hospitalization risk (HR 1.9, 95% CI 1.8-2.1), with those hospitalization rates reaching 29.4, 22.8, and 48.7%, respectively, across groups.

“Patients with AS plus ATTR-CA experience worse clinical outcomes than patients with AS only. Increased awareness of these coexisting conditions may help facilitate earlier screening and improve prognosis,” suggested study authors led by Ahmad Masri, MD, MS, of Oregon Health & Science University in Portland. Their report was published in the Journal of the American Heart Association.

Masri’s team noted the challenges of a timely and accurate diagnosis of ATTR-CA, which is unfamiliar to many physicians and is often mistaken for other conditions like AS. “Signs and symptoms of low-flow, low-gradient AS, such as hypertrophic myocardial remodeling, diastolic dysfunction, atrial fibrillation, and reduced longitudinal myocardial shortening, may resemble those of ATTR-CA,” according to Masri and colleagues.

The AS population in particular holds some attraction as a pool for ATTR-CA screening, as ATTR-CA has previously been observed in 8-16% of those referred for cardiac MRI or transcatheter aortic valve replacement for AS. The extent of the overlap between AS and ATTR-CA is not clear, however, as it is possible that they share other common pathophysiologic risk factors or that one may lead to the other.

In the present report, several factors common among people with both ATTR-CA and AS were heart failure, cardiac arrhythmias, cardiomegaly, carpal tunnel syndrome, chronic kidney disease, and autonomic and peripheral neuropathy.

“Recognizing these associated features could help clinicians identify patients who may benefit from screening for ATTR-CA, or may allow for electronic medical record-based risk scores to help determine who should be screened for ATTR-CA,” according to an accompanying editorial by Brett Sperry, MD, of University of Missouri-Kansas School of Medicine and St. Luke’s Mid America Heart Institute in Kansas City.

ATTR-CA, also commonly called transthyretin amyloid cardiomyopathy (ATTR-CM), is a progressive cardiomyopathy characterized by extracellular accumulation of plasma ATTR amyloid in the myocardium. For asymptomatic patients diagnosed with early-stage disease, it can take just a few years to progress to clinical heart failure or other cardiovascular complications.

“More vigilant recognition and earlier diagnosis and treatment of ATTR-CA are considered imperative to improving patient outcomes. Achieving these goals is particularly important given the poor prognosis … and the availability of disease-modifying therapy that is most effective early in the disease course,” study authors wrote.

Just 2 months ago, the FDA approved acoramidis (Attruby), another TTR stabilizer for treating wild-type or variant ATTR-CM.

During the study period covered by Masri and colleagues, the FDA had approved the TTR stabilizer tafamidis (Vyndaqel or Vyndamax) for wild-type (or hereditary) ATTR-CM. The investigators noted that ATTR-CA patients may have also taken inotersen (Tegsedi) and patisiran (Onpattro) during the study spanning 2015 to 2021, though neither hereditary transthyretin amyloidosis drug is specifically indicated for cardiac patients.

Too little pharmacy data was available to conduct an analysis of outcomes by use of disease-modifying therapy.

“The onus is on us as the providers to correctly diagnose these patients and treat both their AS and ATTR-CA,” Sperry stressed. “While the overall prevalence may be decreasing due to evolving clinical practices, recognizing this entity remains crucial for optimizing outcomes in both disease states.”

Masri’s group had conducted a retrospective analysis using insurance claims data from over 355,000 individuals, all adults at least 60 years old with medical coverage with at least one of the two conditions. Billing codes indicated an AS-only diagnosis in 97.3%, ATTR-CA only in 2.4% — and both AS and ATTR-CA in 0.3%.

“While this is a small percentage of patients in the cohort, it is the largest number of patients with both diseases currently published in the literature,” Sperry pointed out.

The dual diagnosis group tended to be the oldest subgroup by a few years (average 78.6 years vs 74.3 with ATTR-CA only and 77.9 with AS only), and this cohort had the most men (59.1% vs

Without sufficient information about AS severity, Masri and colleagues took aortic valve replacement at first diagnosis as a surrogate for severe AS. In this subgroup of patients, apparently severe AS plus ATTR-CA was associated with excess mortality (HR 1.4, 95% CI 1.1-1.8) but not heart failure hospitalization (HR 1.1, 95% CI 0.9-1.3) compared with severe AS alone.

The lack of granular data and echocardiograms was a major limitation of the study. Various biases could have also had a hand in the pool of people who ended up in the cohort.