Updating the Definition of PAH
I am curious whether experts still distinguish between primary pulmonary hypertension and secondary pulmonary hypertension when it comes to treating a specific patient, or do they simply follow the NYHA/WHO functional classification (FC) for all patients, which was developed after 1997? Also, in what circumstances (if any) would an expert treat a patient with NYHA FC I, and what agents would be used?
Andrew F. Shorr, MD, MPH
Uniformed Services University of the Health Sciences, Bethesda, Maryland
The classification scheme describing pulmonary arterial hypertension (PAH) has recently been revised. Primary pulmonary hypertension is now referred to as idiopathic pulmonary arterial hypertension (IPAH). Grouped along with IPAH in this new schema are some secondary causes of and diseases associated with PAH. Examples of processes found in this category include: connective tissue disease, HIV, portal hypertension, and drug-related causes. An alternative category exists to encompass pulmonary hypertension associated with chronic lung disease and/or hypoxia. Chronic thromboembolic pulmonary hypertension is grouped in yet another category. In short, the classification system attempts to be more based on underlying pathology and pathophysiology rather than on whether the disease is "primary" or "secondary." The value of this system is that it helps clinicians to realize that not all forms of what has been called secondary PAH arise due to the same events and that some traditionally secondary forms of PAH share much with "primary pulmonary hypertension" while others do not. The concept of "secondary" causes of PAH, though, can remain helpful. It may force physicians to remember the extensive list of diseases associated with PAH. Hence, it leads to consideration of the complex evaluation required as part of the diagnostic approach to PAH.
From a therapeutic perspective, splitting PAH into primary and secondary causes may result in confusion. In certain forms of PAH related to underlying lung disease, the main treatment approach is focused on optimizing treatment for that disease and ensuring oxygenation is adequate rather than immediate consideration of systemic anticoagulation and pulmonary vasodilator therapies. Conversely, in other forms of secondary PAH (eg, scleroderma), the role for treatments directed at the pulmonary vasculature is more evident.
Readers should note, however, that therapeutic approaches to PAH are rapidly evolving. PAH has been shown to be a major cause of morbidity and mortality in certain forms of interstitial lung disease. As a result, consideration of agents like sildenafil may be warranted. In fact, some studies suggest these options may be helpful in these types of PAH. Additionally, bosentan and sildenafil have been evaluated for thromboembolic PAH. Put simply, as newer alternatives become available for PAH therapy, they are being evaluated in many disease states that reach beyond IPAH.
As to treatment of the NYHA/WHO Class I subject: currently recommended algorithms for the diagnosis and treatment of PAH are generally restricted to subjects with Class III or IV disease. All recently completed randomized controlled trials of agents for PAH treatment have required Class II symptoms or greater. Even with this potential to enroll Class II patients, the proportion of such individuals in these trials has been rather small (on average < 10%). Hence there is a paucity of data to guide practice in these and Class I subjects. Unfortunately, because of the natural history of the disease, though, few patients present with less than Class III disease.
Question
I am curious whether experts still distinguish between primary pulmonary hypertension and secondary pulmonary hypertension when it comes to treating a specific patient, or do they simply follow the NYHA/WHO functional classification (FC) for all patients, which was developed after 1997? Also, in what circumstances (if any) would an expert treat a patient with NYHA FC I, and what agents would be used?
Response from the Expert
Andrew F. Shorr, MD, MPH
Uniformed Services University of the Health Sciences, Bethesda, Maryland
The classification scheme describing pulmonary arterial hypertension (PAH) has recently been revised. Primary pulmonary hypertension is now referred to as idiopathic pulmonary arterial hypertension (IPAH). Grouped along with IPAH in this new schema are some secondary causes of and diseases associated with PAH. Examples of processes found in this category include: connective tissue disease, HIV, portal hypertension, and drug-related causes. An alternative category exists to encompass pulmonary hypertension associated with chronic lung disease and/or hypoxia. Chronic thromboembolic pulmonary hypertension is grouped in yet another category. In short, the classification system attempts to be more based on underlying pathology and pathophysiology rather than on whether the disease is "primary" or "secondary." The value of this system is that it helps clinicians to realize that not all forms of what has been called secondary PAH arise due to the same events and that some traditionally secondary forms of PAH share much with "primary pulmonary hypertension" while others do not. The concept of "secondary" causes of PAH, though, can remain helpful. It may force physicians to remember the extensive list of diseases associated with PAH. Hence, it leads to consideration of the complex evaluation required as part of the diagnostic approach to PAH.
From a therapeutic perspective, splitting PAH into primary and secondary causes may result in confusion. In certain forms of PAH related to underlying lung disease, the main treatment approach is focused on optimizing treatment for that disease and ensuring oxygenation is adequate rather than immediate consideration of systemic anticoagulation and pulmonary vasodilator therapies. Conversely, in other forms of secondary PAH (eg, scleroderma), the role for treatments directed at the pulmonary vasculature is more evident.
Readers should note, however, that therapeutic approaches to PAH are rapidly evolving. PAH has been shown to be a major cause of morbidity and mortality in certain forms of interstitial lung disease. As a result, consideration of agents like sildenafil may be warranted. In fact, some studies suggest these options may be helpful in these types of PAH. Additionally, bosentan and sildenafil have been evaluated for thromboembolic PAH. Put simply, as newer alternatives become available for PAH therapy, they are being evaluated in many disease states that reach beyond IPAH.
As to treatment of the NYHA/WHO Class I subject: currently recommended algorithms for the diagnosis and treatment of PAH are generally restricted to subjects with Class III or IV disease. All recently completed randomized controlled trials of agents for PAH treatment have required Class II symptoms or greater. Even with this potential to enroll Class II patients, the proportion of such individuals in these trials has been rather small (on average < 10%). Hence there is a paucity of data to guide practice in these and Class I subjects. Unfortunately, because of the natural history of the disease, though, few patients present with less than Class III disease.
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