Current methods for screening, diagnosing, and managing patients with pulmonary arterial hypertension (PAH), a disease that was recognized only in the 1950s, are often inadequate. For too many patients, a diagnosis arrives too late, resulting in significant patient mortality.

As for the management of this disease, targeting multiple pathological pathways seems to yield some benefit, but many experimental studies are still in their early stages. 

Read more about PAH etiology


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PAH has 4 main characteristics: pulmonary vascular endothelial dysfunction, smooth muscle proliferation, fibrosis, and in situ thrombosis that often leads to death. A team of American researchers who conducted a literature review recently summarized the latest developments surrounding PAH care in the Journal of Investigative Medicine. We will look at some of their findings in this article with regards to the diagnosis of PAH. 

Identifying PAH Early 

Physicians recognize that one of the best ways to treat an illness is to first identify it through accurate screening tests. Scientists have proposed a screening assessment for PAH by identifying a few key factors: 

  • Presence of telangiectasias
  • Positive anticentromere antibody 
  • Elevated NT-proBNP (N-terminal-prohormone B-type natriuretic peptide)
  • Elevated serum urate
  • Right axis deviation observed on electrocardiography (ECG)
  • Forced vital capacity (FVC) %/diffusing capacity for carbon monoxide (DLCO) % <1.6 on pulmonary function test.

Patients with high scores should then undergo an echocardiogram to assess the right atrium and the tricuspid regurgitation jet velocity. Patients who are heavily suspected of having PAH based on echocardiography findings should undergo right heart catheterization to confirm the diagnosis.

In addition to these screening methods, scientists are increasingly turning their attention to genetic analysis and serum biomarkers. For example, patients who have a family history of heritable PAH are advised to undergo genetic screening to identify any PAH-associated mutations.

One of the most important mutations in PAH is that of bone morphogenetic protein receptor 2 (BMPR2), which is associated with a high risk of developing PAH. Other mutations of interest include a mutation in the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) gene, which is commonly observed with pulmonary veno-occlusive disease and a poorer prognosis. 

Screening and Diagnostic Methods

There are a number of ways that physicians can screen and monitor for PAH, some of which have been tried and tested while others are more novel. Tracking serum biomarkers, such as proBNP and BNP, are useful to evaluate disease severity and prognosis.

However, medical researchers are attempting to dig deeper to uncover more secrets regarding the status of PAH in patients; for example, attention is turning towards serum biomarkers that can distinguish PAH caused by left heart disease from pulmonary vascular resistance. A large study involving 1129 plasma proteins managed to identify “nine replicable and prognostic proteins for [idiopathic] PAH independent of NT-proBNP levels,” according to the authors of this review. Furthermore, the authors of the review found that adding these biomarkers to existing screening tests substantially improved their predictive ability. 

Read more about PAH diagnosis

Exercise testing is one of the oldest screening tests for PAH that is still widely used today. It is used to determine the severity of exertional symptoms since exertional dyspnea is a classical characteristic of PAH. The physiology of exertional dyspnea can be summarized as follows: the lack of oxygen during exertion cannot be compensated in patients with PAH due to their low stroke volume; this causes an early transition to anaerobic metabolism, characterized by lactic acidosis in the peripheral tissues. In addition, arterial hypoxemia is commonly observed, with low mixed venous oxygen saturation and low alveolar-arterial diffusion of oxygen in affected patients.

Another alternative to echocardiography is the (more expensive) cardiac magnetic resonance imaging (CMRI), which has been touted as being more accurate in assessing right ventricular morphology to establish it at baseline and at subsequent follow-ups. While we all know that echocardiography depends heavily on the expertise of the operator as well as the quality of acoustic windows, CMRI does away with this uncertainty.

As the authors of this review wrote, “[CMRI] is reproducible and accurate and allows for [right ventricular] assessment in a standardized manner. [CMRI] can be used for diagnosing intracardiac shunts, aberrant pulmonary vascular morphology, left-sided disease, and other congenital anomalies.” 

As physicians increasingly recognize the diversity of PAH etiology, invasive cardiopulmonary exercise testing (iCPET) has been recommended as a means of getting a better picture of PAH patients with underlying cardiac, muscular, or lung disease. The use of iCPET is the most beneficial in PAH patients with a suspected component of exertional postcapillary PAH due to left heart disease, those with exercise-induced PAH, and patients with PAH who cannot exercise due to preload limitations.

The testing is performed with pulmonary artery and radial artery catheters, and “provides an assessment of exercise capacity and quantifies the relative contributions of any respiratory, cardiovascular, and metabolic dysfunction,” as well as “provides a unique opportunity to identify early stages of pulmonary vascular disease and low left ventricular diastolic reserve,” according to Huang et al. 

Better Data Save Lives 

The screening and diagnostic methods for patients with PAH mentioned in this article play a vital role in helping physicians make critical decisions regarding the level of medical intervention needed. Coupled with advancements in PAH management, the end result should be a better quality of life for patients with PAH and their caretakers.  

References

Deshwal H, Weinstein T, Sulica R. Advances in the management of pulmonary arterial hypertensionJ Investig Med. 2021;69(7):1270-1280. doi:10.1136/jim-2021-002027

Huang W, Resch S, Oliveira RK, Cockrill BA, Systrom DM, Waxman AB. Invasive cardiopulmonary exercise testing in the evaluation of unexplained dyspnea: insights from a multidisciplinary dyspnea center. Eur J Prev Cardiol. 2017;24(11):1190-1199. doi:10.1177/2047487317709605