A stylized computer rendering of a human heart and heartbeat.

Early cardiac amyloidosis remains bad news without treatment

For asymptomatic patients diagnosed with amyloid transthyretin cardiomyopathy (ATTR-CM) at an early stage, it may take a few years to progress to clinical heart failure or other cardiovascular complications, according to a longitudinal cohort study that also found that early treatment was 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 symptoms of heart failure at baseline.

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

Survival was 96.5% at 1 year and fell to 82% at 5 years, they reported in JACC: Cardio-oncology.

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

“Although our findings should ideally be confirmed in randomized studies, our findings provide support for considering early initiation of stabilizing agents in asymptomatic patients with ATTR-CM,” Gonzalez-Lopez’s group said.

Progressive cardiomyopathy, ATTR-CM is an increasingly recognized cause of heart failure due to advances in non-invasive imaging techniques. The good news is that treatment is available, although inaccessible to many.

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

However, once tafamidis hit the market, it became “the most expensive heart drug in history” and was only affordable with financial assistance for some patients.

Gonzalez-Lopez and her colleagues noted that clinical studies are underway for other potential ATTR-CM treatments. These include another TTR stabilizer, acoramidis, and gene silencing candidates patisiran, vutrisiran and eplontersen.

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

“The only way to have a significant impact on the long-term results of ATTR CA [cardiac amyloidosis] is to initiate effective therapy before major structural damage occurs,” according to Daniel Lenihan, MD, of the Saint Francis Healthcare System in Cape Girardeau, Missouri, and Richard Cheng, MD, MSc, of the 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 disease. problem,” they said. asked in an accompanying editorial.

The Gonzalez-Lopez group’s report was based on records from six centers that specialize in amyloidosis. The study cohort consisted of 118 people who underwent genetic testing, 78.8% of them men and a median age of 66 years.

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

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

Ultimately, 56 people were treated during follow-up: 53 received TTR stabilizers like tafamidis and diflunisal, 13 received genetic silencer, and two underwent liver transplantation. It took an average of 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 received and who did not receive TTR-stabilizing treatment. In addition, the observational analysis may have been confounded.

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    Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow


The study was funded by grants from the Instituto de Salud Carlos III.

Gonzalez-Lopez revealed relationships with Pfizer and Proclara, as well as institutional research and educational support from Pfizer, BridgeBio and Alnylam.

Lenihan disclosed relationships with Bridge Bio and Intellia. Cheng did not disclose any relationship with the industry.

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