Ventilation abnormalities appear to play a more important role in transthyretin amyloid cardiomyopathy (ATTR-CM)-associated shortness of breath than cardiac output abnormalities, according to a recently published study in ESC Heart Failure.
In most cases of heart failure, shortness of breath is a consequence of the heart’s insufficient capacity to pump blood to the rest of the body; the authors aimed to prove that in ATTR-CM, shortness of breath is more dependent on ventilation abnormalities.
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 authors aimed to use symptom-limited maximal cardiopulmonary exercise testing (CPET) and compared parameters between patients with ATTR-CM and patients with chronic heart failure.
Read more about ATTR-CM signs and symptoms
The main parameters used for the purposes of the study included peak oxygen consumption (VO2) and the relationship between minute ventilation (VE) and carbon dioxide production (VCO2), referred to as the VE/VCO2 slope.
The peak oxygen consumption reflected the highest amount of oxygen the body can consume during exercise. The VE/VCO2 slope showed how quickly the body can dispose of C02 during exercise, and a very high slope reflected a ventilation problem.
Researchers compared CPET parameters among 251 patients with ATTR-CM and their chronic heart failure matches.
Results showed that patients with ATTR-CM had a significantly higher VE/VCO2 slope and a reduced VO2. The authors observed that VO2 reduction correlated with body mass index (BMI) and age, while VE/VCO2 was correlated with N-terminal brain natriuretic peptide levels (NT-BNP).
“In conclusion, we showed that CPET is feasible in amyloid cardiomyopathy regardless of the amyloid type and that, in amyloid patients, ventilation inefficiency is the major determinant of exercise limitation,” the authors said.
The authors hypothesized that ventilation abnormalities in ATTR-CM are multifactorial. Increased ventricular stiffness due to amyloid deposition increased the pressure in the pulmonary artery. Furthermore, a damaged lung membrane could have prevented adequate oxygen and CO2 diffusion. It is also possible that patients with ATTR-CM had a blunted C02 production during exercise, which can increase the V/VCO2 slope.
The authors suggested that the findings could be used to guide therapeutic strategies in patients with ATTR-CM. Such strategies could include the use of drugs intended for pulmonary hypertension or a more aggressive use of diuretics.