A proposed approach to consider the evolution of Nice classification of PH 2013-2021
The NICE classification of PH (as seen below) is based on clinical phenotyping and provides a useful and complete approach. However, a non-expert may draw the conclusion that all patients can be easily classified on this basis and can be allocated into a group and subgroup with confidence. This is not necessarily the case.
There are two difficulties with this approach:
- The reality is that many patients may demonstrate clinical features in-keeping with more than one of the clinical groups or subgroups. This is an important concept because such an individual may have a shared classification, including one where there is benefit of treatment with targeted PH therapy.
- Moreover, it raises the question as to whether shared molecular mechanisms of disease can operate across a clinical classification. The tabular format of the NICE classification gives no indication as to the relative numbers of patients falling into each classification group – this would be useful information for the non-expert trying to understand PH.
GROUP 1 PULMONARY ARTERIAL HYPERTENSION
1.1 Idiopathic PAH
1.2 Heritable PAH
1.2.2 ALK-1, ENG, SMAD9, CAV1, KCNK3 1.2.3 Unknown
1.3 Drug & toxin induced
1.4 Associated with:
1.4.1 Connective tissue disease
1.4.2 HIV Infection
1.4.3 Portal Hypertension
1.4.4 Congential Heart Diseases
1’ Pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis 1’’ Persistent Pulmonary Hypertension of the newborn (PPHN)
Group 2 PULMONARY HYPERTENSION DUE TO LEFT HEART INFLOW/ OUTFLOW TRACT OBSTRUCTION & CONGENITAL CARDIOMYOPATHIES
2.1 Left Ventricular Systolic Dysfunction
2.2 Left Ventricular Diastolic Dysfunction
2.3 Valvular Disease
2.4 Congenital/Acquired Left Heart Inflow/Outflow Tract Obstruction & Congenital Cardiomyopathies
GROUP 3 PULMONARY HYPERTENSION DUE TO LUNG DISEASES &/OR HYPOXIA
3.1 Chronic Obstructive Pulmonary Disease
3.2 Interstitial Lung Disease
3.3 Other Pulmonary Diseases With Mixed Restrictive 3.4 Sleep-Disordered Breathing
3.5 Alveolar Hyperventilation Disorders
3.6 Chronic Exposure to High Altitude
3.7 Developmental Lung Diseases
GROUP 4 CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION (CTEPH)
GROUP 5 PULMONARY HYPERTENSION WITH UNCLEAR MULTI-FACTORIAL MECHANISMS
5.1 Haematologic Disorders: Chronic Haemolytic Anaemia, Myeloproliferative Disorders,Spleenectomy
5.2 Systemic Disorders: Sarcoidosis, Pulmonary Histiocytosis, Lymphangioleiomyomatosis 5.3 Metabolic Disorders: Glycogen Storage Diseases, Gaucher disease, Thyroid disorders 5.4 Other: Tumoral obstruction, fibrosing mediastinitis, Chronic renal failure, segnetal PH
One approach to address these two areas is to construct a Venn diagram, with each circle approximating to the likely number of patients within each group as a first step. This is illustrated in figure 1 below.
The circles can then be overlapped, as in figure 2, to demonstrate that an individual patient could have shared clinical features of more than one clinical group, and the size of the overlap approximating to the size of this population of PH patients. Figure 2 clearly demonstrates that some patients classified in groups 2, 3, 4, and 5 will also have features consistent with group 1 disease. This is consistent with current evidence, and examples of this would be a patient with chronic thromboembolic pulmonary hypertension with significant arteriopathy in the non-obstructed vessels and with a good response to targeted medical therapy. Or a patient with group 3 pulmonary hypertension responding to medical therapy.
Finally, figure 3 below demonstrates that using this approach the number of patients categorised as having group 1 disease (PAH), thus potentially amenable to evidence based medical therapy, is greater than might initially be considered.