Global longitudinal strain (GLS) and tactile and thermal quantitative sensory testing (QST) could detect cardiac nerve fiber abnormalities before symptom onset in patients with amyloid transthyretin cardiomyopathy (ATTR-CM), enabling early treatment, according to a study recently published in the Orphanet Journal of Rare Diseases.
“GLS and QST findings demonstrated an early involvement of the heart and small nerve fibers even many years before PADO [predicted age of disease onset] with a parallel impairment among the two systems (cardiac and small fibers) at least in the earliest stage of disease,” the study said.
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.
In light of the increasing importance of early diagnosis since the introduction of disease-modifying therapy for ATTR-CM, the study aimed to determine if GLS and QST could provide early indexes of cardiac and neurological compromise in asymptomatic patients carrying transthyretin gene (TTR) mutations.
Read more about ATTR-CM testing and diagnosis
Researchers enrolled 16 TTR-mutation carriers without any ATTR-CM symptoms or echocardiographic findings. The predicted age of disease onset of the enrolled population was between 15 and 30 years.
GLS revealed that more than 50% of patients had reduced cardiac strain. This finding reflected the effect of amyloid deposition, which impairs the heart’s ability to contract. QST revealed that the majority of patients had small instances of nerve fiber damage. The authors observed GLS reduction correlated with QST abnormalities.
The findings suggested that cardiac and neurologic damage go hand in hand in the early stages of ATTR-CM.
Altered GLS changes alone are not enough to initiate disease-modifying treatment in TRR-mutation carriers; however, most experts consider that patients with abnormalities in two instrumental tests have ATTR-CM and are eligible for treatment.
“Can carriers, displaying abnormal QST and GLS, be considered as ‘converted’? Can they access to a ATTRv treatment (tetramer stabilizer or gene silencers)? Are they at risk of soon conversion?,” the authors asked. “These questions are still unsolved and only the follow-up of these patients can clarify the usefulness of a combined approach with GLS and QST in the ‘conversion’ diagnosis.”
