Table 2:
Phenotyping Tools and Applications in Pulmonary Hypertension: Current Practice and Future Directions
| Component(s)/Tool(s) | Examples of Current Practice | Examples of Future Directions |
|---|---|---|
| Medical history | High index of suspicion | Diet |
| Physician history, questionnaires | Family history | Environmental exposures |
| Physical examination | Height, weight, BP | Waist-to-hip ratio, waist circumference |
| Anthropometrics | Capillaroscopy: Retinal, nailfold, sublingual | |
| Medical devices | ||
| Hemodynamic | PAP, PAOP | TP (PAM to PAOP) gradient |
| Right heart catheterization, hemodynamics | CO | LVEDP before and after volume infusion |
| PVR | PA stiffness | |
| Vasodilator testing | Pulmonary vascular impedance | |
| Portal venous pressure | ||
| Molecular phenotyping | HIV | Glucose, CRP, IL-1, IL-6, vWF, coagulation factors, T-cell responsiveness, SNPs, PBMC gene expression, proteomics, autoimmune antibodies, estrogen levels, circulating endothelial cells |
| Biochemical, serology, immunologic, tissue, genetics | ANA (and other connective tissue serologies) | |
| LFT | ||
| Functional and morphological phenotyping | Walk distance | Desaturation index/burden |
| 6-min walk, Echo, CXR, CT, MRI, PET, angiogram, ECG, lung function, PSG, pathology | RV function, RVSP, RVE, RAE, LVEF | RV mass |
| FEV1, FEV1/FVC, DlCO | Lung perfusion | |
| AHI | RV glucose uptake | |
| CT pulmonary vascular volume | ||
| 3D echo | ||
| QTc intervals | ||
| Biopsy (lung, heart, peripheral muscle), tissue/cell morphology | ||
| Metabolic and ischemia phenotyping | Coronary flow in RVH | |
| Nuclear perfusion imaging, or 18F-fluorodeoxyglucose PET | Phosphocreatine-to-ATP ratio | |
| Fatty acid oxidation | ||
| Extracellular matrix products | ||
| Iron metabolism | ||
| Biomarkers for phenotyping | Troponin | |
| Fasting glucose, triglycerides, HDL cholesterol | ||
| Circulating endothelial progenitor cells | ||
| Circulating microvesicles | ||
| Use of existing population data | Predictive algorithms from registries | |
| Local, national, and international registries |
Definition of abbreviations: 3D = three-dimensional; AHI = apnea–hypopnea index; ANA = anti-nuclear antibody; BP = blood pressure; CO = cardiac output; CRP = C-reactive protein; CT = computed tomography; CXR = chest X-ray; DlCO = diffusion lung capacity for carbon monoxide; echo = echocardiography; HDL = high-density lipoprotein; LAE = left atrial enlargement; LFT = liver function tests; LVEDP = left ventricular end-diastolic pressure; LVEF = left ventricular ejection fraction; MRI = magnetic resonance imaging; PA = pulmonary artery; PAM = pulmonary artery mean; PAP = pulmonary artery pressure; PAOP = pulmonary artery occlusion pressure; PAP = pulmonary artery pressure; PBMC = peripheral blood mononuclear cell; PET = positron emission tomography; PSG = polysomnogram; PVR = pulmonary vascular resistance; RV = right ventricular; RVE = right ventricular enlargement; RVH = right ventricular hypertrophy; RVSP = right ventricular systolic pressure; SNPs = single-nucleotide polymorphisms; TP = transpulmonary; vWF = von Willebrand factor.
Note: Table E3 provides an example of how this phenotyping approach can be used to identify and characterize a specific (in this case maladaptive RV) phenotype. Table E4 provides examples of data used to identify the phenotype examples discussed in this document.