Issues with tiny heart blood vessels may contribute to damage in PAH
Study: People with condition often experience heart disease, chest pain
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People with pulmonary arterial hypertension (PAH) often have abnormalities in the coronary microvasculature, or the tiny blood vessels that are needed to deliver oxygen and nutrients to muscle cells in the heart, a small study shows.
Importantly, problems with these blood vessels may contribute to heart disease and chest pain in people with PAH, data suggested.
The study, “Coronary pathophysiology in idiopathic pulmonary arterial hypertension,” was published in JCI Insight.
Precise underlying mechanisms of PAH not fully understood
PAH is a disorder marked by increased pressure in the vessels that carry blood from the heart through the lungs. This puts strain on the heart, particularly the right ventricle, which pumps blood to the lungs to pick up oxygen. Although it’s well established that PAH causes heart damage, the precise underlying mechanisms are not fully understood.
The heart is a muscle that constantly works, and heart muscle cells require a lot of oxygen and nutrients to function properly. As such, the heart contains tiny blood vessels, known as the coronary microvasculature, that carry oxygen- and nutrient-rich blood to the heart’s own cells. Problems with these vessels can lead to heart damage and angina (chest pain), both of which are common in PAH.
In this study, a team led by scientists in the U.K. evaluated whether PAH affects the health of these tiny blood vessels and whether parameters of microvascular function are associated with PAH severity.
To find out, they enrolled 11 people with PAH (73% women; mean age 47) and 15 people without the disease (73% women; mean age 58.3). All were undergoing right heart catheterization, an invasive procedure used to assess the health of the heart and lung blood vessels.
During this procedure, specialized tests were used to measure the health of the coronary microvasculature. All of the PAH patients had idiopathic disease, meaning the underlying cause is unclear.
Coronary microvascular dysfunction highly prevalent in PAH group
The researchers specifically examined two measures of coronary microvascular health: the index of microcirculatory resistance (IMR) and coronary flow reserve (CRF). IMR assesses how difficult it is for blood to flow through these tiny vessels, while CRF reflects how efficiently a blood vessel responds to increased blood flow demand.
Data showed that PAH patients had significantly higher average IMR scores than people without PAH. The PAH group also had lower CRF scores, but this difference failed to reach statistical significance. In fact, eight of the 11 PAH patients had IMR scores above normal, and six had abnormally low CRF scores.
“Coronary microvascular dysfunction was highly prevalent in the [idiopathic] PAH group: 73% of participants had an increased microvascular resistance in one or more coronary arteries and half (55%) had a reduced coronary flow reserve,” the researchers wrote.
Statistical analyses showed that higher IMR scores and lower CRF scores were associated with a larger right ventricle, but only the latter link reached statistical significance. In PAH, the right ventricle tends to become enlarged due to stress.
As such, these data indicate that poorer flow through the coronary microvasculature is associated with more severe heart disease in PAH, the scientists noted.
Invasive testing appeared safe in this patient population
The researchers also highlighted that the invasive testing used in this study didn’t cause any noteworthy safety problems for the PAH patients. This shows that this type of testing “appears to be feasible and safe in this population when performed by experienced cardiologists,” they wrote.
To assess whether this microvascular dysfunction was linked to a particular structural abnormality in PAH, the researchers also analyzed heart tissue from four deceased people with PAH and five deceased people without PAH.
These analyses indicated that, in the final stages of the disease, PAH is marked by significantly fewer small vessels in the heart, and this reduction was significantly associated with heart enlargement.
Altogether, these data indicate that right ventricle damage in PAH “appears to be associated with microvascular dysfunction, which in turn may contribute to [low oxygen in the heart] and disease progression, warranting further investigation,” the scientists wrote.
In addition, the new protocol to assess coronary microvasculature function “was feasible and safe in patients undergoing clinically indicated right heart catheterization,” and “this approach provides a platform to determine whether therapies targeting PAH can enhance [heart] microvascular function,” the team concluded.
