Anu Balakrishnan MD, DM
Consultant Rheumatologist, Telicherry Co-operative Hospital, Telicherry, Kerala
In rheumatology practice, we see CTD-associated pulmonary artery hypertension (PAH), PAH associated with ILD, Veno-occlusive disease, and chronic thromboembolic hypertension. Let us dive into the history of PAH from the initial reports to the latest classification.
Early studies describe the clinical picture and autopsy findings and correlate them. Although the eponym for PAH is attributed to Dr. Abel Ayerza, there are reports of PAH dating back decades before his description. Ayerza’s patient had a chronic cough with expectoration, dyspnea, and cyanosis, leading to death. The post-mortem showed right ventricular hypertrophy, thickened bronchial wall with secretions, hyperplasia of the pulmonary arteries, and multiple thrombi. He termed the disease “Cardios Negros”, meaning black heart. After Ayerza described the disease, physician Escudera noted the co-existence of black cardiac disease with syphilis. In 1913, Dr. Arillaga presented a series of 11 patients with a similar clinical presentation. Dr Warthrin, who had immense work on Syphilis, also noted a similar clinical picture with syphilitic mesenteritis of pulmonary arteries.
It was Dr. Oscar Brenner, a British pathologist, in 1935, who did a pathological study in 100 similar cases and identified the heterogeneity of pulmonary hypertension (PH), including pulmonary artery remodelling in the absence of syphilis. With the help of a crude apparatus, he could measure the systolic pressure in pulmonary arteries, but people rejected his theory. He advocated using the term “pulmonary hypertension” instead of the eponym.
In 1940, Dr. Terrance East described the loud S2, right axis deviation in the ECG, and an enlarged right ventricle and pulmonary artery on X-ray. He confirmed hypertrophy of the right ventricle. Around the same time, pathologists from Guy’s hospital studied similar patients and termed it ‘idiopathic right ventricular hypertrophy’. Pulmonary hypertension from Mitral stenosis, Bilharziasis(schistosomiasis), gold miners, mountain dwellers, and chronic thrombosis were reported from across the world.
The introduction of right heart catheterisation by Dr. Frossman, and later its modification by Andre Cournand and Dickinson Richards, helped define the pathology of pulmonary hypertension. Paul Wood categorised PH into passive PH (high venous pressure), hyperkinetic PH (left-to-right shunting), and Vaso-occlusive PH before this. However, with RHC in place, the hypoxic response to pulmonary resistance and PAP measurements was performed.
Classification of PH and introduction of primary pulmonary hypertension happened in the WHO 1975 Geneva meeting, following the PH epidemic after aminorex use. The clinical definition was a PAP of≥25 mmHg. Over the years, molecular pathways and genetic mutations have been identified, and early identification has become a necessity, leading to an update in the definition as mean PAP > 20 mmHg and a pulmonary vascular resistance of ≥3 Wood units. The latest 2019 WHO clinical classification has five groups and multiple subgroups.
