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For asymptomatic patients diagnosed with early-stage transthyretin amyloid cardiomyopathy (ATTR-CM), it can take just a few years to progress to clinical heart failure or other cardiovascular complications, according to a longitudinal cohort study that also found early treatment to be associated with greater survival.

The retrospective study followed the natural history and prognosis of early-stage variant or wild-type ATTR-CM diagnosed in 118 consecutive patients without heart failure symptoms at baseline.

Over a median 3.7 years of follow-up, 38 people developed heart failure symptoms, 32 died, and two required cardiac transplantation. Additionally, 20 received pacemakers, 13 developed atrial fibrillation, and one had a stroke, according to Esther Gonzalez-Lopez, MD, PhD, of Hospital Universitario Puerta de Hierro in Madrid, and colleagues.

Survival was 96.5% at 1 year and fell to 82% at 5 years, they reported in .

The investigators found that treatment with TTR stabilizers was associated with significantly improved survival on multivariable analysis (adjusted HR 0.18, 95% CI 0.06-0.55). Treatment also correlated with delayed progression to heart failure without meeting statistical significance.

"Although our findings would ideally need to be confirmed in randomized studies, our results provide support to consider early initiation of stabilizing agents in asymptomatic patients with ATTR-CM," Gonzalez-Lopez's group said.

A progressive cardiomyopathy, ATTR-CM is an increasingly recognized cause of heart failure due to advances in noninvasive imaging techniques. The good news is that treatment is available, albeit inaccessible for many.

In 2019, the FDA approved tafamidis (Vyndaqel or Vyndamax) for wild-type (or hereditary) ATTR-CM. The indication was not restricted to patients with overt heart failure despite approval being based on the phase III ATTR-ACT trial that showed that TTR stabilizer's clinical benefits in people who had already progressed to symptomatic heart failure.

Once tafamidis went on the market, however, it became known as the "most expensive cardiac medication in history" and was affordable only with financial assistance for some patients.

Gonzalez-Lopez and colleagues noted that clinical studies are ongoing for other potential ATTR-CM treatments. These include another TTR stabilizer, , and gene-silencing candidates , , and .

Like the tafamidis trial, these studies are limited to symptomatic individuals.

"The only way we will meaningfully impact the long-term outcomes of ATTR CA [cardiac amyloidosis] is to initiate effective therapy before major structural damage has occurred," according to Daniel Lenihan, MD, of Saint Francis Healthcare System in Cape Girardeau, Missouri, and Richard Cheng, MD, MSc, of University of Washington in Seattle.

"We need to continue to explore how to systematically detect the development of disease in other organs that may be involved initially or use genetic screening tools to identify those with specific variants and, thus, get to the 'root' of the problem," they urged in an .

The report by Gonzalez-Lopez's group was based on records from six specialized amyloidosis centers. The study cohort consisted of 118 people who underwent genetic testing, with 78.8% men and a median age of 66.

Although exercise testing was not required of study participants, the lack of symptomatic heart failure at baseline was supported by fairly low NT-proBNP, preserved systolic function, and moderately increased average left ventricular wall thickness.

The authors observed that 18 individuals were already on treatment at baseline despite the purported absence of heart failure symptoms.

Ultimately, 56 people were treated during follow-up: 53 receiving TTR stabilizers like tafamidis and diflunisal, 13 receiving a genetic silencer, and two undergoing liver transplantation. It took a median 5 months from diagnosis to initiation of stabilizers, Gonzalez-Lopez and colleagues found.

They cautioned, however, that there was likely room for selection bias regarding who did and did not get TTR-stabilizing therapy. Additionally, the observational analysis may have been subject to confounding.

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