PAH Risk Assessment

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Frequent, multiparameter risk calculations serve as the foundation for treatment decisions

PAH is a serious, progressive disease. Although monitoring a patient’s symptoms is an important aspect of care, RV dysfunction can occur before disease progression becomes apparent from your patient’s FC and 6MWD assessments. That’s why routine objective monitoring of many parameters is essential to your patient’s care.1,2

According to treatment guidelines, risk assessment at diagnosis and then every 3 to 6 months is a required step in PAH care that allows you to3,4

  • Identify your patient’s prognosis and treatment goals
  • Determine your patient’s initial treatment regimen
  • Monitor your patient’s response to treatment
  • Identify RV changes before before symptomatic progression
  • Escalate therapy to improve risk status

According to the 2018 WSPH treatment guidelines, today's treatment goal for patients with PAH is to achieve and/or maintain low-risk status.4

Hear from an expert

“Based on databases that have included thousands of patients … I think the multiparameter approach is really critical because this is a very complex disease and there are many different predictors, including how the patient is feeling, whether or not their right ventricle is failing, what their symptoms are like, syncope, how dyspneic they are, what their Functional Class is.”

-Dr. Vallerie McLaughlin
University of Michigan, Ann Arbor

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Dr. Raymond Benza:

In today's program, we will be discussing the importance of risk assessment and pulmonary arterial hypertension management. According to the PAH treatment guidelines, risk assessments should be driving our initial therapy choices as well as any changes in therapy. So let's get started. So Val, can you describe to me what risk assessment is all about in pulmonary arterial hypertension?

Dr. Vallerie McLaughlin:

Yeah. Ray. I think that we as cardiologists have really incorporated risk assessment into really many different diseases. We use different scores for NSTEMIs and STEMIs, and CHA2DS2-VASc for AFib. We live this, this is really something that is important to objectively care for patients. And over the years, we have learned about the important parameters that are prognostic in patients with pulmonary arterial hypertension. We've learned from many databases that have included thousands of patients, the parameters that assess a patient's risk or the severity of their illness and what their likelihood is of having an event over time. I think the multiparameter approach is really critical because this is a very complex disease and there are many different predictors, including how the patient is feeling, whether or not their right ventricle is failing, what their symptoms are like, syncope, how dyspneic they are, what their Functional Class is. Those are all clinical assessments of the patients. Echo has not been incorporated as much as I would like to see it.

We are really just more recently getting savvy about quantitating right ventricular function. So if you look at the registries, the Echo parameters that are included most often include right atrial area and the presence of a pericardial effusion. I think we both know how that right ventricle function is really critical in terms of the outcomes of PAH patients. And then of course, hemodynamics are important. They define the disease and also reflect the function of the right ventricle. And so when we talk about a multiparameter risk assessment, we're looking at many of those different parameters and trying to assess whether we think our patient is at low, intermediate, or high risk over the ensuing years. And we learned from each registry that no matter what the treatment is, if we can get a patient to a low-risk status, their 5-year mortality is very minimal and that should be our goal for the patients to reassess their risk and to drive them into that low-risk status. Ray, is this your approach as well?

Dr. Raymond Benza:

It is my approach. And I think you really eloquently described the available nuances that we take into consideration when we do these assessments of risk, including very importantly, the multiparameter approach. We never hang our hat on just one variable. And I also wanted to really emphasize the piece about imaging because, as we'll talk about it a little bit later, many of the contemporary tools that we have lack sophisticated imaging parameters as part of them. And I think the tools that we have and that we use and that we will describe later, have to be really used in conjunction with some of these other newer things that are coming out that we think are important, but achieving low risk and using the multiparameter approach, I think of the 2 salient issues that I really would like our practicing clinicians to take away from this.

Risk assessment can provide timely guidance for treatment

According to treatment guidelines, achieving and maintaining low-risk status is the treatment goal for patients with PAH.3,4 Patients who achieve this goal improve their likelihood of survival, particularly when this goal is met within the first year of diagnosis. PAH can progress rapidly without outward signs of worsening. A formal risk assessment every 3 to 6 months is needed to catch disease progression early and to help you treat to low-risk status.4

Meeting low-risk criteria within 1 year shown to improve 5-year survival

In the French Registry, patients (N=1017) were assessed by the number of low-risk criteria present at first re-evaluation. Low-risk parameters measured were WHO/NYHA FC I/II, 6MWD >440 m, RAP <8 mm Hg, and CI ≥2.5 L/min/m2. Patients who achieved low-risk status for all 4 parameters at first follow-up within 1 year after diagnosis had 91% transplant-free survival over 5 years.5

Kaplan-Meier transplant-free PAH survival risk assessment graph
Image Description

Transplant-free survival estimates at follow-up (P<0.001)5

  • 4 low-risk criteria: Transplant-free survival (%) is ~96% at 3 years and ~91% at 5 years
  • 3 low-risk criteria: Transplant-free survival (%) is ~92% at 3 years and ~82% at 5 years
  • 2 low-risk criteria: Transplant-free survival (%) is ~80% at 3 years and ~63% at 5 years
  • 1 low-risk criteria: Transplant-free survival (%) is ~67% at 3 years and ~52% at 5 years
  • 0 low-risk criteria: Transplant-free survival (%) is ~42% at 3 years and ~34% at 5 years
Adapted from: Hoeper MM, et al. Eur Respir Rev. 2014;23(134):450-457.

Aim for low risk to help improve your patient’s likelihood of survival

Treating to low-risk status can help you give your patient a better long-term prognosis. The lower your patient’s risk status, the higher their chance of survival over the next 5 years.5-8

If your patients are not at low-risk, escalate therapy by adjusting their treatment plan with additional therapies in accordance with treatment guidelines to help them get there.4

How does risk status affect quality of life?

Read Article Summary

Key criteria of the multiparameter risk assessment

You already perform these tests when you examine your patients, but calculating a risk score enables you to consolidate that information into a risk status that helps you assess your patient's treatment plan. You can evaluate whether your patient's treatment plan is doing enough, and the next steps needed to help your patient achieve their treatment goal.

The parameters below are common across multiple risk assessment methodologies.5-8

NT-proBNP/BNP levels

NT-proBNP and BNP levels are biomarkers of heart strain and possible heart failure that can be measured with a simple blood test. Levels of these biomarkers inversely correlate with survival; higher levels mean a poorer prognosis for your patient.9 In REVEAL Lite 2, BNP/NT-proBNP level was the most predictive noninvasive variable of survival.8 The low-risk goals for NT-proBNP and BNP are <300 ng/L and <50 ng/L, respectively.

A normal BNP/NT-proBNP level has a 98% sensitivity to exclude the presence of these intermediate-/high-risk factors5:

  • RAP >8 mm Hg
  • CI <2.5 L/min/m2
NT-proBNP and normal BNP levels low risk goal marker

6MWD

The 6MWT plays a key role in evaluating exercise capacity.3 Your patient’s 6MWD provides information on how PAH impacts their ability to perform daily activities. Additionally, 6MWD is widely used as a primary or secondary endpoint in randomized controlled trials for PAH. Download your guide to learn more about administering the 6MWT. The low-risk goal for 6MWD is >440 m.3

6MWD low risk goal of less than 440m

Functional Class

FC is a measure of how PAH symptoms restrict daily activities.10 Patients are assigned to 1 of 4 classes based on self-reported activity levels and symptoms. Remember, your patients may adjust their activity levels to accommodate their PAH symptoms. It’s important to be aware that patients may feel better because they’re less active. The low-risk goal for Functional Class is FC I or II.3

Functional class goal of FC I or II

Download an intake form to monitor your patient's symptoms at each appointment.

Download Intake Form (PDF)

WHO FC classifications10

I

No limitation of physical activity from PAH. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope.

II

Slight limitation of physical activity from PAH. Patient is comfortable at rest, but ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope.

III

Marked limitation of physical activity from PAH. Patient is comfortable at rest, but less than ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope.

IV

Inability to carry out any physical activity without symptoms. Patient has signs of right heart failure. Dyspnea and/or fatigue may be present at rest. Discomfort is increased by any physical activity and may result in syncope.

Hemodynamics and imaging

In PAH, deterioration of the RV can happen before decline in other outward measures of risk such as FC and 6MWD.1,2 Monitoring of the RV through tests and imaging such as Echo and RHC are essential for detecting disease progression. The low-risk goal for Echo is RA area <18 cm2 and no pericardial effusion. The low-risk goal for hemodynamics is RAP <8 mm Hg, CI ≥2.5 L/min/m2, and SvO2 >65%.

Low risk goal for echo and hemodynamics in PAH patients

Formal multiparameter risk assessment is essential for accurately assessing your patients3

According to treatment guidelines, risk assessment is required every 3 to 6 months4 to accurately treat and monitor your patients. In multiple studies, clinical gestalt has been shown to be a poor substitute for formal risk assessment.11,12

Gestalt vs formal risk calculation

Insights from an international survey of clinical practice

In a study of 365 charts from 90 HCPs, only 20% of patients assessed to be at low risk were calculated to be at low risk.11

  • When evaluated using gestalt, 80% of patients thought to be low risk were assigned to a higher risk category when risk was formally calculated.

See comparison of gestalt and formal risk calculations from a chart review of 90 PAH-experienced cardiologists and pulmonologists.

Retrospective chart analysis in US patients with FC II PAH

In a study of 153 FC II patients, many of whom were thought to be low risk via gestalt, more than half were classified as intermediate or high risk based on formal risk calculation.12

  • Among FC II patients thought to be low risk when evaluated using gestalt, 64% were assigned to a higher risk category when risk was formally calculated using the French Noninvasive method.

See analysis of risk assessment in FC II patients on mono- and dual therapy.

Chart showing the calculated risk status of patients assessed to be low risk by Gestalt
Image Description

Calculated risk status of patients assessed to be low risk by gestalt (N=118)

Gestalt:

  • 80% reassigned from low risk

Calculated:

  • ~10% high risk
  • ~70% intermediate risk
  • ~ 20% low risk

Calculate risk with these resources

The PAH Initiative provides print and online resources to make multiparameter risk calculation even easier. Choose the resource that works best for your practice.

Online Risk Calculators
Risk Assessment Tear Pads

Hear from an expert

“It is not uncommon that our patients sort of start compensating for themselves and adjust to a new way of life. In fact, there was a recent retrospective chart analysis that looked at 153 Functional Class II patients. And remember Functional Class II is just one of the parameters that we look at, but these are patients who are basically saying they’re OK. But when you do objective assessments on them, a very high proportion of them are really technically at intermediate risk, or some even at high risk.”

-Dr. Vallerie McLaughlin
University of Michigan, Ann Arbor

Podcast icon
Click to expand transcript

Dr. Raymond Benza:

Why is it so important to be proactive in assessing patients and adding therapies when needed? And I know we talked a little bit that the last question, but given the progressive nature of the disease, are patients at risk for disease progression, even when symptoms are absent?

Dr. Vallerie McLaughlin:

Well, Ray, PAH is a progressive disease. It's a disease with a high risk of mortality, even in patients who are on therapy. It is not uncommon that our patients sort of start compensating for themselves and adjust to a new way of life. In fact, there was a recent retrospective chart analysis that looked at 153 Functional Class 2 patients. And remember Functional Class 2 is just one of the parameters that we look at, but these are patients who are basically saying they're okay. But when you do objective assessments on them, a very high proportion of them are really technically at intermediate risk, or some even at high risk.

There's also that one paper that I love to cite. I think it's from the Amsterdam group, that does serial walks and MRIs and clinical assessments. And you'll look and see at their patients, the ones who deteriorate, and you will see changes in their MRI before they start telling you their symptoms are worsening.

So, I think we need to, again, rely on the multiparameter assessment, and we really need objective data to try to assess these patients' risk and, again, drive them into that low-risk status.

Dr. Raymond Benza:

Yeah, that's a great point. If you think of this disease as a continuum, really, symptoms are really late manifestation of progression. So things could be going on, cellular changes, changes in hemodynamics and resistance, and even subtle decompensation of the right heart, that may not be felt at the time that it's happening, really trying to put together this multimodality approach, even in the asymptomatic patients, is really, really important to make sure they are truly at low risk, not only for mortality, but for morbidity too. Because remember, a lot of the scoring systems that we use are really focused on mortality, but you want to get into systems that also give you that risk of morbidity. And you want your patients to be at low risk, both for mortality and morbidity. So that's really important when you make the assessments, like you mentioned.

Dr. Vallerie McLaughlin:

Yeah, I think, Ray, it's really important to mention that, if you wait too long, sometimes you never catch up.

Dr. Raymond Benza:

Exactly.

Dr. Vallerie McLaughlin:

Right? We've seen this in clinical trials. We've seen this with placebo groups in clinical trials, that when therapy is delayed, they just don't improve as much as the patients who got active therapy early on. We've seen this in meta-analysis that patients, if you let their 6-minute walk deteriorate too much, they never catch up.

And, so, I think that is a really great argument for us to be more proactive about those treatment goals and about the timing of those assessments and getting to those goals.

Multiple registries support the prognostic utility of risk stratification5-8,13,14

Establishing PAH Prognosis
6MWD=6-minute walk distance; 6MWT=6-minute walk test; BNP=brain natriuretic peptide; CI=cardiac index; Echo=echocardiogram; FC=Functional Class; HCP=healthcare provider; NT-proBNP=N-terminal pro-brain natriuretic peptide; NYHA=New York Heart Association; RA=right atrium; RAP=right atrial pressure; RHC=right heart catheterization; RV=right ventricle; SvO2=mixed venous oxygen saturation; WHO=World Health Organization.References: 1. Besinque GM, et al. Am J Manag Care. 2019;25(3 suppl):S47-S52. 2. van de Veerdonk MC, et al. Chest. 2015;147(4):1063-1071. 3. Galiè N, et al. Eur Heart J. 2016;37(1):67-119. 4. Galiè N, et al. Eur Respir J. 2019;53(1):1801889. 5. Boucly A, et al. Eur Respir J. 2017;50(2):1700889. 6. Hoeper MM, et al. Eur Respir J. 2017;50(2):1700740. 7. Kylhammar D, et al. Eur Heart J. 2018;39(47):4175-4181. 8. Benza RL, et al. Chest. 2019;156(2):323-337. 9. Fijalkowska A, et al. Chest. 2006;129(5):1313-1321. 10. Rubin LJ. Chest. 2004;126(1 suppl):7S-10S. 11. Simons JE, et al. Adv Ther. 2019;36(9):2351-2363. 12. Sahay S, et al. PLoS One. 2020;15(11):e0241504. 13. Benza RL, et al. Circulation. 2010;122(2):164-172. 14. Benza RL, et al. Chest. 2012;141(2):354-362.