Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) exhibited diverse patterns of heart failure that often deviated from standard screening guidelines, highlighting the need to broaden diagnostic criteria for the disease, according to a recent study published in the Annals of Medicine.
Current recommendations focus on identifying ATTR-CM in patients with preserved ejection fraction and unexplained left ventricular hypertrophy. But the study revealed that most patients had reduced ejection fraction or other atypical presentations of heart failure.
What is ATTR-CM?
Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is a rare progressive disease of the heart muscle that leads to congestive heart failure. It occurs when the transthyretin protein produced by the liver is unstable. Symptoms include fatigue; shortness of breath; irregular heart rate or palpitations; swelling of the legs, ankles and stomach; brain fog; wheezing; and dizziness. It often goes underdiagnosed because of a lack of awareness and knowledge of the disease. There is currently no cure for ATTR-CM.
The study results underscored the importance of considering a broader range of heart failure phenotypes when screening for ATTR-CM. Expanding diagnostic criteria to include patients with reduced ejection fraction and left ventricular dilatation could improve early detection and treatment outcomes for this complex condition.
Read more about ATTR-CM testing and diagnosis
“Our findings could be influenced by selection and referral biases, potentially leading to a higher-than-anticipated proportion of patients with HFrEF [reduced ejection fraction] and LV [left ventricular] dilatation,” study authors said.
The study examined 135 patients diagnosed with ATTR-CM, predominantly older men (mean age 78 years) with wild-type ATTR-CM (89%). Echocardiography data showed that 60% of participants had a left ventricular ejection fraction below 50%, with a significant subset presenting with reduced ejection fraction.
In addition, 43% of patients showed left ventricular dilatation, and 10% had both reduced left ventricular ejection fraction and severe left ventricular dilatation—features commonly associated with dilated cardiomyopathy rather than ATTR-CM.
Patients with left ventricular ejection fraction below 50% often displayed more advanced disease markers such as higher NYHA functional class and elevated biomarkers such as N-terminal pro-B-type natriuretic peptide and troponin. These indicators reflected greater strain on the heart and more severe disease progression compared to those with preserved ejection fraction.
Despite these findings, only 26% of patients in the cohort would have met screening criteria based solely on preserved ejection fraction and hypertrophy.
The study observed a wide spectrum of phenotypes of heart failure, from preserved ejection fraction with normal left ventricular size to reduced ejection fraction with severe left ventricular dilatation. Moderate left ventricular dilatation was noted in 30% of patients, and severe left ventricular dilatation was noted in 13% of patients. This variability underscored that ATTR-CM cannot be reliably identified using a single presentation of heart failure or echocardiographic pattern.
No significant differences in characteristics of heart failure were found between male and female patients, although men made up the majority of the cohort. The researchers also noted no substantial differences in diagnostic trends over time, suggesting a persistent underrecognition of ATTR-CM in patients with diverse presentations of heart failure.
