What Role Does Echocardiography Play in PAH Diagnosis?
This is Andy Shorr with a pulmonary and critical care literature update. I would like to talk about an article by Parent and colleagues that was published in the July 7 issue of the New England Journal of Medicine. These investigators, who are part of an established group of experts in pulmonary arterial hypertension (PAH) wanted to focus on the prevalence of PAH in patients with sickle cell disease and evaluate the role for echocardiography in the diagnosis of PAH.
For some time, there has been controversy about the role of echocardiogram as a screening and diagnostic test for PAH. Most experts would agree that an echocardiogram that does not show any elevation in the pulmonary artery systolic pressure excludes clinically meaningful PAH. There are certainly patients in whom that is not true, and it may be particularly true in patients with interstitial lung disease, but in general, if the echocardiogram does not suggest an elevated tricuspid regurgitant (TR) jet velocity then PAH is probably not an issue for the patient.
The question then becomes, when the TR jet velocity is high (> 2.5 m/s), and the estimated pulmonary artery systolic pressure is > 25 mm Hg, does the patient have PAH? Parent and coworkers looked at echocardiography in a group of patients who were considered at high risk for PAH because they had sickle cell disease. There has been a lot of focus on PAH and sickle cell disease recently, especially on the role for sildenafil in the management of these patients. Patients with sickle cell disease who were randomly assigned to sildenafil actually had worse outcomes than patients who did not receive sildenafil, in the recent National Institutes of Health trial that was stopped early because of concerns about harm.
In the analysis by Parent and colleagues, they looked at about 400 patients with sickle cell disease across multiple institutions in France and performed echocardiography on all patients. About 96 (25%) of 398 patients had elevated TR jet velocities and were considered to have PAH in terms of the echocardiographic screening. Of great interest, when they went on to catheterize these patients, the true prevalence of PAH was about 6%. The sensitivity and specificity of the echocardiogram for the diagnosis of PAH were catastrophically abysmal.
They actually found, when they catheterized the patients, that about half of the patients also had elevated pulmonary capillary wedge pressures, suggesting that half of the PAH was due to pulmonary venous hypertension or left ventricular dysfunction. The true incidence of PAH in these patients was actually quite low.
These investigators concluded that the echocardiogram alone is not sufficient for making the diagnosis of PAH in patients with sickle cell disease. When they looked at the correlation between the estimated pulmonary artery systolic pressure and the measured pulmonary artery pressure, it was less than 65%. The r was less than 0.65, suggesting some correlation, but not a very strong one. This is important because many times in pulmonary medicine, we get asked to evaluate patients for PAH solely on the basis of an echocardiogram.
If we look at the data from some of our national registries recently, particularly the REVEAL (Registry to Evaluate Early And Long-term PAH Disease Management), there are certainly patients who are being treated for idiopathic PAH or other World Health Organization (WHO) Group I syndromes, purely on the basis of an echocardiogram. This study and multiple other studies that have been recently published, such as one by Rich and colleagues several months ago, clearly confirm that the echocardiogram is not up to par for this kind of diagnostic modality. It is not sufficient to make a diagnosis of PAH. You must send the patient for a right heart catheterization.
This is particularly true when we are dealing with diseases like idiopathic PAH and other WHO Group I syndromes. If you diagnose PAH in those settings and you have decided to initiate therapy, you are exposing the patient to the risks of those therapies, whether it's with a phosphodiesterase inhibitor or some other kind of agent, like an endothelin-receptor agonist, or a prostacyclin analogue. Those agents are not without risk. They are certainly not without side effects, and they are most certainly associated with excess costs.
As an analogy (which I am going to borrow from a colleague of mine), you would never send someone to cardiopulmonary bypass without a left heart catheterization, so why would you think about diagnosing PAH without a right heart catheterization? Right heart catheterization remains the gold standard for this disease. We do not have good surrogates yet to tell us that we don't need to proceed to right heart catheterization if our suspicion for PAH is high, on the basis of any number of variables, particularly the echocardiogram.
Parent and colleagues also found that when they stratified patients (those who had no PAH, those who had PAH due to pulmonary venous causes because their wedge pressure was high, and those who had true PAH), the patients who had true PAH had B-type natriuretic peptide (BNP) levels that were exceedingly high -- in the 1000 pg/mL range -- so clearly, this suggests that right ventricular dysfunction is at play in these patients and that you can capture that by measuring the BNP. Perhaps eventually, we may look at BNP with some combination of echocardiographic findings to really hone in on who needs a right heart catheterization, but even those 2 variables alone will not be sufficient to replace the right heart catheterization. Recall that a right heart catheterization is generally a low-risk procedure.
Parent and colleagues provide confirmatory data for an important question in pulmonary medicine, especially with the proliferation of echocardiography throughout the hospital and throughout the country. Sometimes, I joke with my house staff that the only indication for an echocardiogram is a pulse because we over-order these tests. The problem with over-ordering screening tests is you have to deal with the results, and so we need to understand the limitations of the echocardiogram in diagnosing PAH. At this point, you cannot make a diagnosis of PAH on the basis of an echocardiogram. You must proceed to a heart catheterization because that is clearly what the data suggest.
This article was in the July 7 issue of the New England Journal of Medicine. This is Andy Shorr from Washington, DC.
This is Andy Shorr with a pulmonary and critical care literature update. I would like to talk about an article by Parent and colleagues that was published in the July 7 issue of the New England Journal of Medicine. These investigators, who are part of an established group of experts in pulmonary arterial hypertension (PAH) wanted to focus on the prevalence of PAH in patients with sickle cell disease and evaluate the role for echocardiography in the diagnosis of PAH.
For some time, there has been controversy about the role of echocardiogram as a screening and diagnostic test for PAH. Most experts would agree that an echocardiogram that does not show any elevation in the pulmonary artery systolic pressure excludes clinically meaningful PAH. There are certainly patients in whom that is not true, and it may be particularly true in patients with interstitial lung disease, but in general, if the echocardiogram does not suggest an elevated tricuspid regurgitant (TR) jet velocity then PAH is probably not an issue for the patient.
The question then becomes, when the TR jet velocity is high (> 2.5 m/s), and the estimated pulmonary artery systolic pressure is > 25 mm Hg, does the patient have PAH? Parent and coworkers looked at echocardiography in a group of patients who were considered at high risk for PAH because they had sickle cell disease. There has been a lot of focus on PAH and sickle cell disease recently, especially on the role for sildenafil in the management of these patients. Patients with sickle cell disease who were randomly assigned to sildenafil actually had worse outcomes than patients who did not receive sildenafil, in the recent National Institutes of Health trial that was stopped early because of concerns about harm.
In the analysis by Parent and colleagues, they looked at about 400 patients with sickle cell disease across multiple institutions in France and performed echocardiography on all patients. About 96 (25%) of 398 patients had elevated TR jet velocities and were considered to have PAH in terms of the echocardiographic screening. Of great interest, when they went on to catheterize these patients, the true prevalence of PAH was about 6%. The sensitivity and specificity of the echocardiogram for the diagnosis of PAH were catastrophically abysmal.
They actually found, when they catheterized the patients, that about half of the patients also had elevated pulmonary capillary wedge pressures, suggesting that half of the PAH was due to pulmonary venous hypertension or left ventricular dysfunction. The true incidence of PAH in these patients was actually quite low.
These investigators concluded that the echocardiogram alone is not sufficient for making the diagnosis of PAH in patients with sickle cell disease. When they looked at the correlation between the estimated pulmonary artery systolic pressure and the measured pulmonary artery pressure, it was less than 65%. The r was less than 0.65, suggesting some correlation, but not a very strong one. This is important because many times in pulmonary medicine, we get asked to evaluate patients for PAH solely on the basis of an echocardiogram.
If we look at the data from some of our national registries recently, particularly the REVEAL (Registry to Evaluate Early And Long-term PAH Disease Management), there are certainly patients who are being treated for idiopathic PAH or other World Health Organization (WHO) Group I syndromes, purely on the basis of an echocardiogram. This study and multiple other studies that have been recently published, such as one by Rich and colleagues several months ago, clearly confirm that the echocardiogram is not up to par for this kind of diagnostic modality. It is not sufficient to make a diagnosis of PAH. You must send the patient for a right heart catheterization.
This is particularly true when we are dealing with diseases like idiopathic PAH and other WHO Group I syndromes. If you diagnose PAH in those settings and you have decided to initiate therapy, you are exposing the patient to the risks of those therapies, whether it's with a phosphodiesterase inhibitor or some other kind of agent, like an endothelin-receptor agonist, or a prostacyclin analogue. Those agents are not without risk. They are certainly not without side effects, and they are most certainly associated with excess costs.
As an analogy (which I am going to borrow from a colleague of mine), you would never send someone to cardiopulmonary bypass without a left heart catheterization, so why would you think about diagnosing PAH without a right heart catheterization? Right heart catheterization remains the gold standard for this disease. We do not have good surrogates yet to tell us that we don't need to proceed to right heart catheterization if our suspicion for PAH is high, on the basis of any number of variables, particularly the echocardiogram.
Parent and colleagues also found that when they stratified patients (those who had no PAH, those who had PAH due to pulmonary venous causes because their wedge pressure was high, and those who had true PAH), the patients who had true PAH had B-type natriuretic peptide (BNP) levels that were exceedingly high -- in the 1000 pg/mL range -- so clearly, this suggests that right ventricular dysfunction is at play in these patients and that you can capture that by measuring the BNP. Perhaps eventually, we may look at BNP with some combination of echocardiographic findings to really hone in on who needs a right heart catheterization, but even those 2 variables alone will not be sufficient to replace the right heart catheterization. Recall that a right heart catheterization is generally a low-risk procedure.
Parent and colleagues provide confirmatory data for an important question in pulmonary medicine, especially with the proliferation of echocardiography throughout the hospital and throughout the country. Sometimes, I joke with my house staff that the only indication for an echocardiogram is a pulse because we over-order these tests. The problem with over-ordering screening tests is you have to deal with the results, and so we need to understand the limitations of the echocardiogram in diagnosing PAH. At this point, you cannot make a diagnosis of PAH on the basis of an echocardiogram. You must proceed to a heart catheterization because that is clearly what the data suggest.
This article was in the July 7 issue of the New England Journal of Medicine. This is Andy Shorr from Washington, DC.
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