Open Access is an initiative that aims to make scientific research freely available to all. To date our community has made over 100 million downloads. It’s based on principles of collaboration, unobstructed discovery, and, most importantly, scientific progression. As PhD students, we found it difficult to access the research we needed, so we decided to create a new Open Access publisher that levels the playing field for scientists across the world. How? By making research easy to access, and puts the academic needs of the researchers before the business interests of publishers.
We are a community of more than 103,000 authors and editors from 3,291 institutions spanning 160 countries, including Nobel Prize winners and some of the world’s most-cited researchers. Publishing on IntechOpen allows authors to earn citations and find new collaborators, meaning more people see your work not only from your own field of study, but from other related fields too.
Right heart cardiac catheterization remains the gold standard for the diagnosis of pulmonary arterial hypertension and is an essential component to classify and characterize the type of pulmonary hypertension. Performing a diagnostic right heart catheterization for the assessment of pulmonary hypertension requires a detailed understanding of waveform physiology, cardiac output assessment, right ventricular afterload evaluation, vasoreactivity testing, and accurate left atrial pressure measurement. Furthermore, right heart catheterization can be used to unmask left heart disease by utilizing fluid challenge testing and exercise right heart catheterization. Additionally, the determination of pulmonary artery compliance, in conjunction with pulmonary vascular resistance, can help provide a more comprehensive assessment of pulmonary artery load and right ventricular afterload. Lastly, hemodynamic information obtained by right heart catheterization can be used as a risk assessment tool to guide management and predict mortality.
University of Missouri School of Medicine, Columbia, Missouri, United States of America
*Address all correspondence to: aaron.miller@health.missouri.edu
1. Introduction
Pulmonary hypertension generally refers to an abnormal elevation of the pulmonary artery pressure, and it represents a complex and multifactorial disease process with significant morbidity and mortality implications for patients. Right heart catheterization remains the gold standard for the appropriate classification and diagnosis of pulmonary hypertension. Accurately diagnosing and classifying pulmonary hypertension requires careful analysis and accurate interpretation of the hemodynamic waveforms obtained during right heart catheterization. Accurate interpretation of hemodynamic data is a powerful skillset that provides important risk assessment information and serves as the basis of treatment decisions that can have a meaningful impact on patient morbidity, mortality, and quality of life.
The World Symposium on Pulmonary Hypertension last convened in 2019 and defined pulmonary hypertension as a mean pulmonary artery pressure (mPAP) >20 mmHg [1]. Hemodynamically, pulmonary hypertension is further classified into pre-capillary, post-capillary, and combined pre- and post-capillary pulmonary hypertension. Pre-capillary pulmonary hypertension is defined as a mPAP >20 mmHg, a pulmonary vascular resistance (PVR) >2 wood units, and a pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg [2]. Post-capillary pulmonary hypertension is generally associated with left heart disease and is defined by a mPAP >20 mmHg, PVR ≤ 2 woods units, PCWP >15 mmHg. Lastly, combined pre- and post-capillary hypertension is characterized by a mPAP >20 mmHg, PVR > 2 woods units, and a PCWP >15 mmHg. Table 1 provides a summary of the different hemodynamic classifications of pulmonary hypertension.
Classification
Hemodynamic criteria
Pre-capillary PH
mPAP>20 mmHg, PAWP≤15 mmHg, PVR > 2 WU
Post-capillary PH
mPAP>20 mmHg, PAWP>15 mmHg, PVR < 2 WU
Combined pre−/post-capillary PH
mPAP>20 mmHg, PAWP>15 mmHg, PVR > 2 WU
Table 1.
Hemodynamic classification of pulmonary hypertension.
This table summarizes the hemodynamic classification of pulmonary hypertension. The mPAP, PAWP, PVR are obtained during the right heart cardiac catheterization.
Source: Eur Heart J. 2022 Oct 11;43(38):3618-3731.
Once the hemodynamic classification is determined, then pulmonary hypertension can be further classified into one of five groups, as outlined in Table 2. To appropriately classify pulmonary hypertension, additional testingis needed to assess for left heart disease, chronic pulmonary disease or sleep-related breathing disorders, chronic thromboembolic disease or other pulmonary artery obstruction, and other disorders such as hematologic disorders, systemic disorders, chronic kidney disease/end-stage renal disease, and fibrosing mediastinitis. Basic testing that is essential for the appropriate classification of pulmonary hypertension includes the following: laboratory testing to assess for HIV, chronic kidney disease, connective tissue disease, and hematologic/systemic/metabolic disorders; complete pulmonary function testing, arterial blood gas analysis, chest X-ray, CT chest imaging, ventilation-perfusion scan, transthoracic echocardiogram, and polysomnography. This initial barrage of testing helps clarify the clinical context with which to interpret the hemodynamic results. Interestingly, only the Group 2 and Group 5 patients have a post-capillary component to their pulmonary hypertension. Groups 1, 3, 4, and 5 can all have a pre-capillary hemodynamic pattern depending on the results of the previously mentioned test results. Therefore, an appropriate classification of pulmonary hypertension requires both the cardiac catheterization results and a thorough clinical evaluation. For many patients, there could be a combination of pulmonary hypertension groups contributing to the development of pulmonary hypertension. For these more complicated, multifactorial cases, identification and optimization of all underlying disorders must be performed as part of a patient’s treatment plan.
Group 1: Pulmonary arterial hypertension (PAH)
1.1 Idiopathic PAH
1.2 Heritable PAH
1.3 PAH associated with drugs/toxins
1.4 Associated with:
1.4.1 Connective tissue disease
1.4.2 HIV infection
1.4.3 Portal Hypertension
1.4.4 Congenital heart disease
1.4.5 Schistosomiasis
1.5 PAH with features of venous/capillary (PVOD/PCH) involvement
1.6 Persistent PH of the newborn
Group 2: Pulmonary hypertension (PH) associated with left heart disease
2.1 Heart failure:
2.1.1 heart failure with preserved ejection fraction
2.1.2 heart failure with reduced ejection fraction
2.2 Valvular heart disease
2.3 Congenital/acquired cardiovascular conditions
Group 3: PH associated with lung diseases and/or hypoxia
3.1 Obstructive lung disease or emphysema
3.2 Restrictive lung disease
3.3 Lung disease with mixed restrictive/obstructive pattern
3.4 Hypoventilation syndromes
3.5 Hypoxia without lung disease (e.g. high altitude)
3.6 Developmental lung disorders
Group 4: PH associated with pulmonary artery obstructions
4.1 Chronic thromboembolic PH
4.2 Other pulmonary artery obstructions
Group 5: PH with unclear and/or multifactorial mechanisms
5.1 Hematological disorders
5.2 Systemic disorders
5.3 Metabolic disorders
5.4 Chronic renal failure with or without hemodialysis
5.5 Pulmonary tumor thrombotic microangiopathy
5.6 Fibrosing mediastinitis
Table 2.
Clinical classification of pulmonary hypertension.
Source: Eur Heart J. 2022 Oct 11;43(38):3618-3731.
Finally, hemodynamic data from a right heart catheterization can be utilized to assess the function and afterload of the right ventricle. Right ventricular failure represents the leading cause of death in pulmonary hypertension patients [3, 4]. Therefore, accurately assessing right ventricular function using hemodynamics is an essential component of treatment planning for pulmonary arterial hypertension. Cardiac output measurements are obtained during right heart catheterization to assess right ventricular function and to help calculate pulmonary vascular resistance and pulmonary artery compliance (PAC). PVR and PAC provide important information regarding right ventricular afterload and can provide crucial information to optimize right ventricular function.
2. Right heart cardiac catheterization: Essential components and evidenced-based measurements for pulmonary hypertension assessment
2.1 Basic setup and supplies
Right heart catheterization remains the gold standard for the diagnosis and classification of pulmonary hypertension. Therefore, completing the right heart catheterization requires expertise in terms of setup and pressure acquisition. The basic essential components of performing a right heart catheterization are a catheter; a transducer; a fluid-filled tubing to connect the catheter to the transducer; a physiologic recorder to display, analyze, print, and store the hemodynamic waveforms [5].
The most common catheter used to measure right heart and pulmonary pressures is the Swan-Ganz catheter. At a minimum, the Swan-Ganz catheter has a distal port for pressure measurements, a proximal port that is located 30 cm from the tip used for manual thermodilution cardiac output measurements, a balloon tip for flotation to the pulmonary artery, and a thermistor at the distal tip which allows for the measurement of temperature changes duringthe thermodilution cardiac output assessment. The Swan-Ganz catheter is generally 110 cm in length and comes in different sizes, usually ranging from 5 to 8 Fr. Also, the Swan-Ganz catheter comes in different types. Usually, the Swan-Ganz catheters that are placed in critically ill patients for hemodynamic assessment include a thermal filament that allows for continuous thermodilution cardiac output monitoring. The Swan-Ganz catheters used in the cardiac catheterization lab do not have the thermistor coil since thermodilution cardiac output measurements in the cardiac catheterization lab can be done manually by infusing chilled saline through the proximal port (Figure 1).
Figure 1.
This image identifies the major components of a Swan-Ganz catheter (Model 782F75M). This type of catheter has a thermal filament that is generally used in a critical care setting for continuous cardiac output monitoring. (Source: Edwards Lifesciences, Irvine, CA, USA).
The transducer and tubing are also important components of accurate hemodynamic assessment. The tubing should be stiff pressure tubing to avoid waveform damping. The transducers are generally table-mounted and fluid-filled. The pressure wave is transmitted through the fluid-filled catheter, through the stiff pressure tubing, and finally to a membrane in the transducer. The pressure transmitted from the catheter deforms the membrane resulting in a change in electrical resistance. This electrical signal is transmitted to the analyzing computer and converted to a graphic representation of the pressure wave (Figure 2).
Figure 2.
This is an image of a transducer. The small black object in the transducer unit is the membrane that deforms creating the electrical signal that generates waveforms. (Source: N Engl J Med. 2017 Apr 6;376(14):e26.)
The Swan-Ganz catheter, tubing, and transducer circuit must be set up appropriately to ensure accurate right heart and pulmonary pressure assessment. Important principles to help optimize setup and data integrity include the following: 1) avoid air, blood, kinks, and soft tubing as these can result in overdamping the signal, 2) use the shortest tubing length possible and avoid the use of numerous stop cocks as this can result in underdamping the waveform. Over- or under-damping results in inaccurate pressure measurements which can compromise the integrity of the waveforms resulting in misdiagnosis or incorrect classification of a patient’s pulmonary hypertension. If the hemodynamic waveforms do not appear normal or the pressures do not make sense physiologically, then a square wave test can be used during the right heart catheterization to determine if the waveforms are over- or under-damped.
Lastly, to ensure the waveform pressures are accurate during set-up, the catheter or transducer should be zeroed and aligned with the mid-thoracic level [6]. At the mid-thoracic level, the catheter is level with the left atrium. Making the transducer level with the left atrium will allow for the most accurate measurement of the pulmonary artery wedge pressure (PAWP). The PAWP is one of the most important determinants when classifying the type of pulmonary hypertension; therefore, obtaining an accurate PAWP is essential for making the appropriate pulmonary hypertension diagnosis and determining the appropriate treatment for the patient.
2.2 Evidence-based measurements recommended to be obtained during right heart catheterization
Ideally, right heart cardiac catheterizations should be performed at an expert pulmonary hypertension center. When the right heart catheterization is performed at an expert center, the frequency of serious events is only 1.1%, and procedure-related mortality is only .055% [7]. In addition to these favorable complication rates, an expert center can review the hemodynamic waveforms and interpret them in the context of the patient’s clinical presentation and diagnostic testing.
During the right heart catheterization, there are hemodynamic parameters that are directly measured and others that are calculated. The measured values are as follows: right atrial pressure, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, mean pulmonary artery pressure, pulmonary artery wedge pressure, cardiac output, mixed venous oxygen saturation measured from the pulmonary artery, arterial oxygen saturation, and systemic blood pressure. The calculated values determined by right heart catheterization results are as follows: pulmonary vascular resistance, pulmonary vascular resistance index, total pulmonary resistance, cardiac index, stroke volume, stroke volume index, and pulmonary artery compliance. Pulmonary vascular resistance is especially important in the classification of pulmonary hypertension; therefore, it must be calculated in all patients undergoing right heart cardiac catheterization [2].
When measuring cardiac output during the right heart catheterization, there are 2 most common methods utilized: 1) indirect Fick, 2) thermodilution cardiac output. The indirect Fick is calculated based on the following formula:
Oxygen content of the blood can be calculated by the following formula:
CaO2=(1.34xhgbxSaO2)+(PaO2x.003)
The same formula can be used to calculate the O2 content of venous blood, but the SvO2 would be used instead of the SaO2 for venous blood. Therefore, in the cardiac catheterization lab, the hemoglobin, SaO2, SvO2 can be easily obtained to determine the arteriovenous oxygen difference (A-VO2). For indirect Fick, the oxygen consumption must be calculated. The Dehmer Formula is the simplest and only requires the patient’s body surface area. Other formulas, such as the LaFarge and Bergstra formulas, can also be used. Direct Fick is considered the gold standard for measuring cardiac output, but this method is not clinically practical since oxygen consumption must be simultaneously measured during the right heart catheterization [2].
Thermodilution cardiac output is the second most common method used for measuring cardiac output, and it is the preferred method for determining cardiac output in pulmonary hypertension patients [8]. Thermodilution cardiac output is determined by injecting 10 mL of chilled normal saline through the proximal port located 30 cm from the catheter tip. The chilled saline causes the blood to transiently cool, creating a decrease in blood temperature that is detected by the thermistor at the distal tip of the Swan-Ganz catheter. The blood eventually warms back to normal with time. This temperature change creates a skewed bell-curve graphic. The area under the bell curve is inversely proportionate to the cardiac output based on the modified Stewart-Hamilton conservation of heat equation. This equation is as follows:
CO(Td)=[(Tb−Ti)xVixK](∫ΔTbxdt)E2
In the numerator of the modified Stewart-Hamilton equation, Tb = blood temperature, Ti = injectate temperature, Vi = injectate volume, and K = correction constant. The denominator of the equation represents the area under the thermodilution curve. Therefore, a large area under the curve will result in low cardiac output. Alternatively, a smaller area under the curve will correspond to normal or high cardiac output. Figure 3 illustrates this important concept about the relationship between the area under the thermodilution curve and the cardiac output.
Figure 3.
These three different graphs represent different thermodilution curves corresponding to a normal, low, and high cardiac index. These curves illustrate the concept that the area under the thermodilution curve are inversely proportionate to cardiac output. (Source: Top Companion Anim Med. 2016 Sep;31(3):100-108.)
The thermodilution and indirect Fick cardiac output measurements were compared in a large clinical trial [8]. The results of this trial demonstrated a poor correlation between indirect Fick and thermodilution. Interestingly, thermodilution cardiac output results correlated significantly to patient mortality, whereas the indirect Fick measurements did not have a mortality correlation. Therefore, thermodilution cardiac output has become preferred since it correlates with patient mortality, whereas indirect Fick does not. The cardiac output range in this study varied from 1.7–7.8 L/m, making thermodilution a reliable measure of cardiac output within the studied range. When comparing direct Fick to thermodilution across the cardiac output range, thermodilution correlated closely to direct Fick in both the low and normal cardiac output groups. Hence, thermodilution can be reliable even in low cardiac output states [9].
Thermodilution cardiac output has been thought to be inaccurate in patients with severe tricuspid regurgitation. In theory, severe tricuspid regurgitation would cause the chilled 10 mL normal saline injectate to recirculate, which would potentially cause a falsely low cardiac output. In reality, this recirculation theory does not seem to be true. When the thermodilution cardiac output method was compared to direct Fick across a spectrum of mild/moderate and severe tricuspid regurgitation patient groups, there was no significant variability in cardiac output measurements, even in the severe tricuspid regurgitation group. Therefore, thermodilution cardiac output can still be used in both low cardiac output states and in patients with severe tricuspid regurgitation.
In some cases, patients with pulmonary hypertension have intra-cardiac shunts. In patients with an intra-cardiac shunt, thermodilution cardiac output is unreliable and should be avoided. In these cases, direct Fick cardiac output assessment is preferred [2].
3. Right heart catheterization: fundamentals of waveform interpretation
The main goal of a hemodynamic study is to accurately reproduce and analyze changes in pressure in a heart chamber or in the pulmonary circulation during the cardiac cycle. The pressure transducer used in the cardiac catheterization procedure contains a diaphragm that generates an electrical current when it is triggered by fluid waves that are transmitted from the heart through the Swan-Ganz catheter tip. This electrical current from the transducer is used to generate pressure waves over time. These generated waves can then be utilized to diagnose and characterize the type of pulmonary hypertension present in a patient.
The waveforms obtained during a right heart catheterization procedure should be carefully analyzed to ensure proper fidelity. Also, the waveforms should be carefully aligned with an electrocardiogram (EKG) to appropriately identify the filling and emptying phases of the cardiac cycle. Furthermore, careful attention to identifying end-expiration is important since this is the respiratory cycle phase where the pulmonary pressures are least impacted by pressure shifts associated with the chest wall and diaphragm. All pressures, especially the PAWP, should be measured at end-expiration without breath holding [2].
3.1 Atrial waveforms
The right atrium and left atrium have similar appearing waveforms; however, the normal pressure in the atria is slightly different. The right atrium is characterized by a relatively low pressure of 2–6 mmHg, while the left atrial pressure is normally 4–12 mmHg.
Generally, an atrial waveform has an “a” wave and a “v” wave as well as an “x” and “y” descent. The “a” wave corresponds to the pressure increase associated with atrial contraction. This first atrial wave usually follows the P wave on EKG by approximately 80 msec. The “x” descent follows the “a” wave and represents the pressure decay associated with atrial relaxation and the downward movement of the atrioventricular (AV) junction that occurs due to ventricular contraction. The “v” wave follows the “x” descent and corresponds to passive venous filling during atrial diastole. This occurs in conjunction with ventricular systole when the tricuspid valve is closed. The “v” wave can be identified as occurring at the end of the T wave of the EKG. The “y’ descent occurs following the “v” wave and represents rapid emptying of the right atrium when the tricuspid valve opens. In a normal clinical setting, the “a” wave is generally taller than the “v” wave. Figure 4 demonstrates how to identify the “a” and “v” waves relative to an EKG on an actual patient.
Figure 4.
This figure represents a right atrial waveform with the “a” and ‘V’ waves labeled relative to the EKG. Image created by Aaron Miller.
Conceptually, the right and left atrial waveforms have “a” and “v” waves and an x and y descent. However, the left atrial waveform does have some important differences compared to the right atrial waveform. First, the fine details of the left atrial waveform are not present due to damping associated with the longer distance the pressure signal is traveling from the left side of the heart to the catheter tip in the pulmonary artery. Second, the “v” wave is generally slightly taller than the “a” wave, related to the slightly higher-pressure gradients on the left side of the heart compared to the right heart. Lastly, there is a much larger delay in the left atrial waves and descents relative to the EKG tracing compared to the right atrium. Again, this reflects the increased distance the signal travels from the left atrium to the catheter tip in the pulmonary artery. The left atrial “a” wave occurs 240 msec after the P wave on EKG. The “v” wave occurs shortly after the T wave on the EKG.
Measuring the left atrial pressure from the pulmonary arteries requires temporary, complete occlusion of the pulmonary artery with the balloon on the tip of the Swan-Ganz catheter. Obtaining a high-quality pulmonary capillary wedge pressure is arguably the most difficult wave to obtain during a right heart catheterization, and it is the most important component to distinguish pre- and post-capillary pulmonary hypertension. Identifying a high-quality PCWP requires a few key components. First, there should be a clearly identifiable “a” and “v” wave. Recognizing a clear “a” and “v” wave can help the provider ensure the balloon is not under-wedged. In the case of an under-wedged waveform, the wave tends to resemble a damped pulmonary artery waveform and loses the “a” and “v” waves. Second, there should be obvious respiratory variation. In the case of an over-wedged waveform, the PCWP waveform tends to flatten and lose clear variability with respiratory effort. Third, when the balloon is deflated in a wedge position, the waveform should quickly return to a pulmonary artery waveform. Fourth, blood gas can be collected from the distal tip of the Swan-Ganz catheter when the catheter tip balloon is inflated. This blood gas sample should have a SpO2 > 90% [10]. Lastly, fluoroscopy can be used to confirm the correct position of the Swan-Ganz catheter tip. The ideal location for the catheter tip on fluoroscopy is below the level of the left atrium in West lung zone 3. Figure 5 visually summarizes the key components of the PAWP waveform.
Figure 5.
This image demonstrates a PAWP waveform. Relative to the EKG, the “a” and ‘V’ waveforms have been identified. Image created by Aaron Miller.
3.2 Right ventricular waveform
Normally, the right ventricle systolic pressure is 20–30 mmHg, and the diastolic pressure is 0–8 mmHg. In the absence of significant tricuspid valve disease, the diastolic right ventricular pressure should be similar to the right atrial pressure. The pressure tracing increases during right ventricular systole. The pressure waveform will then decrease with pressure decay after the systole completes, and the downsloping side of the waveform corresponds to a rapid filling phase. A slow-filling phase precedes the systolic phase of the next cardiac cycle. Figure 6 summarizes the key components of the RV waveform.
Figure 6.
This schematic represents an RV waveform. The red circle corresponds to an increase in pressure associated with systole followed by a rapid decrease in pressure as the RV empties into the PA. The black circle corresponds to the diastolic or filling phase of the RV. Sometimes, there is an “a” wave located at the green arrow that represents atrial kick. Image created by Aaron Miller.
3.3 Pulmonary artery waveform
The pulmonary artery pressure waveform has a normal systolic pressure of 20–30 mmHg and a diastolic pressure of 4–12 mmHg. Table 3 summarizes all of the normal hemodynamic values commonly measured during right heart catheterization. In the setting of a normal pulmonic valve, the systolic pulmonary artery pressure should be similar to the systolic right ventricular pressure. Likewise, the diastolic pulmonary artery pressure is generally slightly higher than the PAWP. Also, one helpful concept that helps differentiate the right ventricular waveform from the pulmonary artery waveform is a diastolic step-up in pressure between the right ventricular diastolic pressure and the pulmonary artery diastolic pressure. This pressure change represents the increased resistance due to the high pulmonary artery surface area. These concepts can help confirm that the recorded hemodynamic pressures during a right heart cardiac catheterization make sense physiologically. Excessive pressure gradients should prompt a close assessment of the waveform quality, and it should prompt a close evaluation of cardiac structure on imaging to explain the gradients. Excessive pressure gradients could represent significant valvular disease.
Normal hemodynamic values obtained during right heart catheterization.
SvO2 is derived from a blood sample collected from the pulmonary artery
PVR = (mPAP-PAWP)/CO
TPR = mPAP/CO
PAC = SV/(sPAP-dPAP)
WU, Wood units
Source: Eur Heart J. 2022 Oct 11;43(38):3618-3731.
Another important component of the pulmonary artery waveform that distinguishes it from the right ventricular waveform is the dicrotic notch found on the curve’s down-sloping side. The dicrotic notch represents the pulmonic valve’s closure, marking the beginning of diastole. Figure 7 provides a schematic that visually highlights the major differences between the RV and PA waveforms.
Figure 7.
This schematic represents the transition from RV to PA during a right heart catheterization and highlights two important difference between the RV and PA waveforms. The red waveform represents the RV pressure. The black circles demonstrate the diastolic step-up that occurs when the catheter tip enters the PA. Also, the green arrow points to the dicrotic notch that is also a characteristic feature of the PA. Image created by Aaron Miller.
4. Right heart catheterization: role and interpretation of vasoreactivity testing, fluid challenge testing, and exercise testing
Vasoreactivity testing plays an important role in evaluating and managing patients with pulmonary arterial hypertension. The main purpose of this test is to determine which patients would benefit from treatment with high dose calcium channel blockers as opposed to traditional pulmonary vasodilators. Based on the most recent guideline recommendations, vasoreactivity testing should be completed in patients with idiopathic pulmonary arterial hypertension, hereditary pulmonary arterial hypertension, and drug/toxin-induced pulmonary arterial hypertension [2]. This vasodilator challenge test can be completed with inhaled iloprost or inhaled nitric oxide. Intravenous epoprostenol can be used but requires incremental dose increases and serial measurements, which can significantly prolong the procedure, making this approach less practical [11]. Intravenous adenosine had been previously listed as an acceptable medication for use during vasoreactivity testing; however, due to frequent side effects, adenosine is no longer recommended.
A positive vasoreactivity test response can be defined by the following criteria: decrease in mPAP by ≥10 mmHg to reach an absolute value in the mPAP to ≤40 mmHg with an unchanged or improved cardiac output. This positive response is not common in patients with PAH. In a study that included 557 patients with Idiopathic PAH, approximately 13% of patients had a positive vasodilator response [11]. In patients with PAH due to causes other than Idiopathic PAH, such as anorexigen use, HIV, connective tissue disease, congenital heart disease, and pulmonary veno-occlusive disease, a sustained positive vasodilator response was rare, with the exception of patients with anorexigen-associated PAH. In patients with anorexigen PAH, there was close to a 10% success rate of sustained response to calcium channel blockers [12]. Patients with the appropriate pulmonary arterial hypertension diagnosis and a positive vasodilator challenge test can be treated with high dose calcium channel blocker therapy. Commonly used calcium channel blockers and acceptable doses are as follows: nifedipine 20 mg 2–3 times daily, amlodipine 15–30 mg daily, diltiazem 120–360 mg twice daily, felodipine 15–30 mg daily. The general approach is to start a low calcium channel blocker dose and gradually increase it as tolerated [11].
There are clinical scenarios where calcium channel blocker therapy may not be an ideal treatment option. Patients with a depressed cardiac output on right heart catheterization, systemic hypotension, known hypersensitivity to calcium channel blockers, history of postural hypotension, hemodynamic instability, bradycardia, or heart block may not tolerate calcium channel blocker therapy. Also, patients who do not undergo vasoreactivity testing or patients with a negative vasoreactivity test should not be started on calcium channel blocker therapy [11, 12, 13, 14, 15].
Lastly, vasoreactivity testing can provide important prognostic information depending on the calcium channel blocker response duration. After initiating calcium channel blocker therapy, patients must be followed closely at intervals of 3–6 months to ensure adequate clinical response. Repeat right heart catheterization is recommended in that follow-up interval to determine if the patient has a persistent vasodilator response and to determine if the patient achieved an ideal hemodynamic improvement defined by mPAP<30 mmHg and PVR < 4 WU. Calcium channel blocker therapy can be increased if there is persistent vasoreactivity or if the patient has not reached ideal hemodynamic improvement. The 5-yr survival in patients who were long-term responders to CCB was >90% [11]. Therefore, vasoreactivity testing can also be used as a tool for predicting mortality.
One important purpose of performing a right heart catheterization in diagnosing PAH is to exclude left heart disease and confidently confirm the presence of pulmonary vascular disease. More recent epidemiologic data from the USA and Europe indicate that PAH is now frequently diagnosed in older patients >65 years old [16]. This older patient population can be much more challenging to confirm PAH due to co-morbid conditions such as essential hypertension, diabetes, atrial fibrillation, and BMI > 30 kg/m2 since these comorbid conditions are also risk factors for heart failure with preserved ejection fraction (HFpEF), coronary artery disease and other left heart issues [17, 18]. Distinguishing pulmonary vascular disease from left heart disease can be challenging, and the pulmonary capillary wedge pressure can be normal in patients with left heart disease who are euvolemic due to optimized diuretic dosing. Fluid challenge testing and exercise testing during the right heart catheterization can help unmask left heart disease and more confidently confirm the presence of pulmonary vascular disease.
The fluid challenge test can be helpful in revealing left ventricular diastolic dysfunction in patients with normal pulmonary capillary wedge pressure and clinical risk factors for left heart disease. Generally, the fluid challenge test is performed by giving approximately 500 mL (7–10 mL/kg) normal saline bolus over 5–10 minutes. If the pulmonary capillary wedge pressure increases to ≥18 mmHg after the fluid challenge, then this would confirm left heart disease [18]. Unfortunately, additional data is needed to better validate this fluid challenge assessment. Also, there is insufficient data assessing the hemodynamic response to a fluid challenge in patients with PAH [19].
The gold standard assessment for cardiopulmonary hemodynamics during exercise and to define exercise PH is the exercise right heart cardiac catheterization [20]. For the purposes of pulmonary hypertension assessment, the main purpose of an exercise right heart catheterization is to assess patients with unexplained dyspnea and normal resting hemodynamics. This test allows early detection of pulmonary vascular disease or left heart disease. Furthermore, exercise hemodynamics can reveal important prognostic and functional information in patients at risk for developing PAH such as systemic sclerosis patients [21]. Exercise right heart cardiac catheterization has been shown to have a safety profile and a complication rate similar to resting right heart catheterization [20].
The exercise right heart catheterization should follow an incremental exercise protocol such as a ramp or step protocol. Repeat hemodynamic measurements should be gathered at predefined time intervals to maximize the clinical utility of the test. The most important hemodynamic variables to be collected during the exercise right heart catheterization include the following: right atrial pressure (RAP), pulmonary artery pressure, pulmonary artery wedge pressure (PAWP), cardiac output, cardiac index, heart rate, and systemic blood pressure. In patients with pulmonary vascular disease, there is a steep rise in mean pulmonary artery pressure relative to the change in cardiac output. The mPAP/CO slope will be >3 mmHg/L/min in patients with early pulmonary vascular disease. Additionally, the PAWP should not increase significantly relative to the patient’s cardiac output making the PAWP/CO slope < 2 mmHg/L/min. Conversely, patients with left heart disease would be expected to have an mPAP/CO slope < 3 mmHg, L/min and a PAWP/CO slope > 2 mmHg/L/min [2]. Additionally, to confirm a diagnosis of HFpEF, the PAWP should increase to >25 mmHg during supine exercise [22] (Table 4).
Classification
Hemodynamic criteria
Exercise changes in PAH
mPAP/CO slope > 3 mmHg/L/min
PAWP/CO slope < 2 mmHg/L/min
Exercise changes in left heart disease
mPAP/CO slope <3 mmHg/L/min
PAWP/CO slope >2 mmHg/L/min
PAWP increase to >25 mmHg
Table 4.
Hemodynamic classification of exercise-induced pulmonary hypertension.
This table summarizes the hemodynamic classification for exercise-induced pulmonary hypertension. The mPAP, PAWP, CO are measured during the right heart cardiac cathterization at consistent intervals during exercise.
5. Right heart catheterization: evaluating right ventricular afterload using pulmonary vascular resistance and pulmonary artery compliance
Normally, the right ventricle (RV) is thin-walled and crescent-shaped, and it is designed to accommodate the entire systemic venous return to the heart while maintaining the same effective stroke volume as the left ventricle. The RV relies on the highly distensible, low resistance pulmonary arteries to accomplish this purpose. In pulmonary arterial hypertension (PAH), the pulmonary arteries become remodeled, causing them to lose their normal distensibility and low impedance, essential in maintaining normal RV function. The changes to the pulmonary circulation from pulmonary vascular disease in PAH result in increased RV afterload and eventual RV failure and death. Measuring RV afterload is an important component of PAH diagnosis and management. In clinical practice, RV afterload can be best understood and measured using the three-element Windkessel model [23], which defines RV afterload in three components: pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAC), and pulmonary arterial impedance (PAI). These three components represent both static and dynamic components of RV afterload.
PVR is the most used parameter of the three components of RV afterload since it is an essential component in the definition of pulmonary arterial hypertension. Interestingly, PVR is estimated to represent approximately 75% of total RV afterload which partly explains why it’s a necessary component to the definition of PAH [24]. PVR represents a static component of RV afterload and is determined by the principles of Poiseuille’s law, which establishes an inverse relationship to the fourth power between the radius of the blood vessel and resistance. Due to the static nature of PVR, it does not account for the pulsatile component of pulmonary circulation or the effect of blood volume [25]. Therefore, assessing RV afterload requires an assessment of both static and dynamic parameters to more accurately determine which patients truly have pulmonary vascular disease.
Pulmonary artery compliance (PAC) is a second important component of RV afterload measurement, and it accounts for approximately one-fourth of the total RV afterload [23]. The PAC is generally distributed throughout the pulmonary circulation and includes both distal and proximal pulmonary vessels. The main, proximal left and right pulmonary arteries together contribute approximately one-fifth of the total PAC. The distal pulmonary arteries contribute the major portion of both resistance and compliance in the pulmonary circulation. Normally, the pulmonary circulation has a high compliance that is designed to handle large blood volume changes with exercise while maintaining a relatively normal pressure. In pulmonary arterial hypertension, pulmonary artery compliance decreases [26, 27], and it correlates with pulmonary hypertension severity [27]. Additionally, a decrease in pulmonary artery compliance has been associated with pulmonary vascular remodeling in the proximal pulmonary arteries [28, 29, 30]. Interestingly, evidence suggests that decreased PAC occurs early in the disease process of PAH and can be present in patients with normal resting pulmonary pressure. In these patients with low PAC and normal resting PA pressures, an exercise right heart catheterization would be needed to unmask exercise-induced pulmonary hypertension [25]. The PAC decreases due to disruption of the internal elastic lamina, which generally occurs prior to pulmonary artery smooth muscle cell hypertrophy and endothelial cell proliferation [31].
Calculating PAC in vivo is challenging, and there are many proposed formulas for measuring arterial stiffness [32]. In clinical practice, PAC is most commonly estimated by the following formula: PAC = stroke volume/pulmonary artery pulse pressure. Pulmonary artery pulse pressure is the difference between systolic and diastolic pulmonary artery pressures. PAC is an important parameter for estimating RV afterload, and it has been shown to be an independent predictor of mortality in patients with PAH, scleroderma-related PAH, and congestive heart failure [26, 33, 34].
Decreasing PAC significantly impacts RV function by increasing pulsatile workload [35]. This increased workload forces the RV to generate increased pressure to eject blood [36]. These changes ultimately lead to increased RV wall stress and increased O2 consumption. Structurally, in response to this increased workload, the RV becomes hypertrophied and dilated, which progresses to reduced cardiac output, ultimately leading to RV failure and death [37, 38]. A decrease in PAC has been independently associated with RV dysfunction, dilation, and hypertrophy [39]. Compared to PVR, the contribution of PAC to RV stroke work index is 1.2–18-fold higher, highlighting the significant contribution of PAC on RV function [39].
The final component of measuring RV afterload is pulmonary artery impedance (PAI). Fundamentally, PAI evaluates the ratio of the pulmonary arterial pressure waveform to the blood flow waveform throughout the cardiac cycle [32]. In essence, PAI represents the opposition of proximal pulmonary arteries to pulsatile blood flow. Therefore, the impedance is another dynamic measurement of RV afterload, and it accounts for the effect of blood mass on RV afterload. Additionally, it factors in the stiffness of the proximal pulmonary arteries. The contribution of PAI on total RV afterload is small and is not routinely used [23]. In clinical practice, the role and relevance of PAI have not been clearly established. More studies are needed to better determine the clinical application of PAI.
6. Right heart catheterization: using hemodynamic results as a risk assessment tool to guide management and predict mortality
Pulmonary hypertension management follows an organized, goal-directed approach to ensure patients are responding favorably to treatment. Risk assessment tools such as REVEAL 2.0 [40], REVEAL Lite 2.0, [41] COMPERA 2 [42], FRENCH Risk Score [43], and the 2015 ESC/ERS Guidelines Risk Tool [44] can be used to assess response to treatment and mortality risk on an ongoing basis. Guidelines in pulmonary arterial hypertension management recommend the regular use of a risk assessment tool when managing and evaluating pulmonary arterial hypertension patients. These risk assessment tools are superior to physician gestalt alone and can provide inciteful and objective information about how well patients are responding to treatment [45]. When patients have not reached a low-risk status based on the risk assessment tools, then the treatment approach should be escalated if appropriate until low-risk status is achieved.
Within the REVEAL 2.0 and the 2015 ESC/ERS Guidelines risk assessment tools, there are hemodynamic variables that have a meaningful and significant impact on mortality as isolated numbers. Also, the change in some of these hemodynamic variables in response to treatment has an impact on patient mortality. In the 2015 ESC/ERS Guideline Risk Assessment tool, there are a few hemodynamic variables with important prognostic significance which are as follows: right atrial pressure (RAP), cardiac index (CI), and SvO2. Conceptually, these variables are markers of RV dysfunction severity which is generally the most common cause of death in patients with pulmonary arterial hypertension. Therefore, preserving RV function is the cornerstone of treatment in patients with pulmonary arterial hypertension. Multiple clinical studies have been performed over the years to confirm that CI>/= 2.5 L/m/m2 is an independent predictor of mortality in patients with PAH [46, 47]. Additionally, patients were more likely to have a worse outcome if the CI did not improve by >/= .5 L/m/m2 or if the CI did not improve by>2.5 L/m/m2. This supports the importance of utilizing hemodynamic data as a marker of mortality but also as a marker of treatment response. Mean RAP >10 mmHg and a SvO2 < 65% at baseline were also associated with higher mortality rates [46]. If the SvO2 increased to >65% on follow-up after treatment for 1 year, patients have a more favorable outcome from a mortality perspective.
Another commonly used risk assessment tool that includes hemodynamic parameters to measure risk and estimate mortality is the REVEAL 2.0 score. In the latest edition of the risk score, the PVR and mean RAP are included in the risk assessment tool. For this score, if the PVR is <5 Wood units, then the patient gets a reduced score which would favor an improved mortality estimation. If the mean RAP is >20 mmHg, then the patient would receive a higher total score which would be associated with worse outcomes. In the original study that established the REVEAL score, a multivariate analysis was completed that established PVR and mean RAP as independent predictors of mortality. In the original study, the PVR cutoff was 32 Wood units [48]. The more recent study that led to the revised REVEAL 2.0 score demonstrated that the reduced PVR cutoff of 5 Wood units improved the calculator’s predictive power as a risk assessment tool. Therefore, targeting a PVR goal of <5 Wood units is in-line with a goal-directed treatment approach.
The role of mPAP as a measurement of estimated mortality has been unreliable in many previous studies; therefore, mPAP is not included in any of the risk assessment scores. Previous studies have shown that the baseline mPAP and change in mPAP after treatment did not show a significant correlation to increased risk of death [46, 47]. The one exception to this trend was patients who were considered positive vaso-responders when challenged with vasoreactivity testing during cardiac catheterization. Long-term responders to calcium channel blockers successfully maintained a mean PAP of <40 mmHg and had a percent change in mPAP of >31% [11]. The patients who were long-term responders to calcium channel blockers had a significantly improved mortality risk compared to those patients who were unable to maintain a positive response to pulmonary vasodilators.
More recently, a study cohort evaluating a population of patients managed in Japan demonstrated that mean PAP did have a significant correlation with mortality. In this study, patients who achieved a minimum mPAP <42 mmHg had lower mortality rates compared to the nonsurvivor patient group. Interestingly, the few patients who reached a minimum mPAP <42 mmHg in the nonsurvivor group were highly likely to die from causes unrelated to PAH. Also, mPAP data was plotted on a ROC curve for this study. The area under the curve for mPAP was the largest compared to other variables tested, such as BNP, cardiac output, and 6-minute walk distance. These results supported the conclusion that a mPAP cutoff of approximately <40 mmHg could be a useful target for improving survival in PAH patients. Perhaps, based on the results of this study, mPAP will become a more generally accepted marker of treatment response and mortality in patients with PAH.
Pulmonary hypertension is a disorder associated with an abnormal elevation of the pulmonary artery pressure, and it represents a complex and multifactorial disease process with significant morbidity and mortality implications for patients. Right heart catheterization remains an essential tool for the appropriate diagnosis and classification of pulmonary hypertension. Performing right heart cardiac catheterization well requires a thorough and methodical approach to ensure all the appropriate supplies are acquired and to ensure the catheterization setup is performed correctly. While obtaining hemodynamic data, careful attention to the waveforms is needed to ensure good data integrity. End-expiratory pressures should be identified and used when interpreting the waveform results. In addition to obtaining waveform data, cardiac output monitoring is performed, preferably using the thermodilution technique. The thermodilution cardiac output can be used in combination with the mPAP and PAWP waveforms to calculate the PVR, which should always be performed when evaluating a patient for pulmonary hypertension. In the appropriate setting, vasoreactivity testing should be performed to identify patients who would be good candidates for calcium channel blocker therapy. The hemodynamic results can also be used to assess right ventricular afterload and to assess the risk of mortality based on risk assessment scoring systems such as REVEAL 2.0 and the 2015 ESC/ERS risk assessment. Overall, the hemodynamics of pulmonary hypertension can be a powerful diagnostic and management tool when performed correctly and comprehensively.
I want to thank my wife, Shauna, and my two kids, Logan and Jillian, for their unwavering support of me and my career.
References
1.Simonneau G, Montani D, Celemajer D, et al. Hemodynamic definitions and updated clinical classification of pulmonary hypertension. The European Respiratory Journal. 2019;53(1):1801913
2.Humbert M, Kovacs G, Hoeper M, et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. European Heart Journal. 2022;43(38):3618-3731
3.Schrier R, Bansal S. Pulmonary hypertension, right ventricular failure, and kidney: Different from left ventricular failure? Clinical Journal of the American Society of Nephrology. 2008;3(5):1232-1237
4.Campo A, Mathai SC, Le Pavec J, et al. Outcomes of hospitalisation for right heart failure in pulmonary arterial hypertension. The European Respiratory Journal. 2011;38(2):359-367
5.Ragosta M. Textbook of Clinical Hemodynamics. 2nd ed. Philadelphia: Elsevier; 2018
6.Kovacs G, Avian A, Olschewski A, Olschewski H. Zero reference level for right heart catheterization. The European Respiratory Journal. 2013;42(6):1586-1594
7.Hoeper M, Lee S, Voswinckel R, et al. Complications of right heart catheterization procedures in patients with pulmonary hypertension in experienced centers. Journal of the American College of Cardiology. 2006;48(12):2546-2552
8.Opotowsky A, Hess E, Maron B, et al. Thermodilution vs estimated Fick cardiac output measurement in clinical practice: An analysis of mortality from the veterans affairs clinical assessment, reporting, and tracking (VA CART) program and Vanderbilt University. JAMA Cardiology. 2017;2(10):1090-1099
9.Hoeper M, Maier R, Tongers J, et al. Determination of cardiac output by the Fick method, thermodilution, and acetylene rebreathing in pulmonary hypertension. American Journal of Respiratory and Critical Care Medicine. 1999;160(2):535-541
10.Viray M, Bonno E, Gabrielle N, et al. Role of pulmonary artery wedge pressure saturation during right heart catheterization: A prospective study. Circulation. Heart Failure. 2020;13(11):e007981
11.Sitbon O, Humbert M, Jais X, et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation. 2005;111(23):3105-3111
12.Montani D, Savale L, Natali D, et al. Long-term response to calcium-channel blockers in non-idiopathic pulmonary arterial hypertension. European Heart Journal. 2010;31(15):1898-1907
13.Opitz C, Wensel R, Bettmann M, et al. Assessment of the vasodilator response in primary pulmonary hypertension. Comparing prostacyclin and iloprost administered by either infusion or inhalation. European Heart Journal. 2003;24(4):356-365
14.Jing ZC, Jiang X, Han ZY, et al. Iloprost for pulmonary vasodilator testing in idiopathic pulmonary arterial hypertension. The European Respiratory Journal. 2009;33(6):1354-1360
15.Baumgartner H, Backer J, Babu-Narayan S, et al. 2020 ESC guidelines for the management of adult congenital heart disease. European Heart Journal. 2021;42(6):563-645
16.Lau E, Giannoulatou E, Celermajer D, Humbert M. Epidemiology and treatment of pulmonary arterial hypertension. Nature Reviews. Cardiology. 2017;14(10):603-614
17.Kittleson M, Panjrath G, Amancherla K, et al. 2023 ACC expert consensus decision pathway on management of heart failure with preserved ejection fraction: A report of the American College of Cardiology Solution set Oversight Committee. Journal of the American College of Cardiology. 2023;81(18):1835-1878
18.Vachiery JL, Tedford R, Rosenkranz S, et al. Pulmonary hypertension due to left heart disease. The European Respiratory Journal. 2019;53(1):1801897
19.D’Alto M, Romeo E, Argiento P, et al. Clinical relevance of fluid challenge in patients evaluated for pulmonary hypertension. Chest. 2017;151(1):119-126
20.Kovacs G, Herve P, Barbera JA, et al. An official European Respiratory Society statement: Pulmonary haemodynamics during exercise. The European Respiratory Journal. 2017;50(5):1700578
21.Zeder K, Avian A, Bachmaier G, et al. Exercise pulmonary resistances predict long-term survival in systemic sclerosis. Chest. 2021;159(2):781-790
22.Pieske B, Tschope C, Boer RA, et al. How to diagnose heart failure with preserved ejection fraction: The HFA-PEFF diagnostic algorithm: A consensus recommendation from the heart failure association (HFA) of the European Society of Cardiology (ESC). European Heart Journal. 2019;40(40):3297-3317
23.Saouti N, Westerhof N, Postmus P, Vonk-Noordegraaf A. The arterial load in pulmonary hypertension. European Respiratory Review. 2010;19(117):197-203
24.Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology. 2013;62(16):e147-e239
25.Thenappan T, Prins K, Pritzker M, et al. The critical role of pulmonary arterial compliance in pulmonary hypertension. Annals of the American Thoracic Society. 2016;13(2):276-284
26.Mahapatra S, Nishimura R, Sorajja P, et al. Relationship of pulmonary arterial capacitance and mortality in idiopathic pulmonary arterial hypertension. Journal of the American College of Cardiology. 2006;47(4):799-803
27.Sanz J, Kariisa M, Dellegrottaglie S, et al. Evaluation of pulmonary artery stiffness in pulmonary hypertension with cardiac magnetic resonance. JACC: Cardiovascular Imaging. 2009;2(3):286-295
28.Dodson R, Morgan M, Galambos C, et al. Chronic intrauterine pulmonary hypertension increases main pulmonary artery stiffness and adventitial remodeling in fetal sheep. American Journal of Physiology. Lung Cellular and Molecular Physiology. 2014;307(11):L822-L828
29.Ooi CY, Wang Z, Tabima D, et al. The role of collagen in extralobar pulmonary artery stiffening in response to hypoxia-induced pulmonary hypertension. American Journal of Physiology. Heart and Circulatory Physiology. 2010;299(6):H1823-H1831
30.Kobs R, Muvarak N, Eickhoff J, et al. Linked mechanical and biological aspects of remodeling in mouse pulmonary arteries with hypoxia-induced hypertension. American Journal of Physiology. Heart and Circulatory Physiology. 2005;288(3):H1209-H1217
31.Wallace W, Nouraie M, Chan S, Risbano M. Treatment of exercise pulmonary hypertension improves pulmonary vascular distensibility. Pulmonary Circulation. 2018;8(3):2045894018787381
32.Ghio S, Schirinzi S, Pica S. Pulmonary arterial compliance: How and why should we measure it? Global Cardiology Science Practise. 2015;2015(4):58
33.Tji-Joong Gan C, Lankhaar J-W, Westerhof N, et al. Noninvasively assessed pulmonary artery stiffness predicts mortality in pulmonary arterial hypertension. Chest. 2007;132(6):1906-1912
34.Campo A, Mathai S, Le Pavec J, et al. Hemodynamic predictors of survival in scleroderma-related pulmonary arterial hypertension. American Journal of Respiratory and Critical Care Medicine. 2010;182(2):252-260
35.Wang Z, Chesler N. Pulmonary vascular wall stiffness: An important contributor to the increased right ventricular afterload with pulmonary hypertension. Pulmonary Circulation. 2011;1(2):212-223
36.Castelain V, Herve P, Lecarpentier Y, et al. Pulmonary artery pulse pressure and wave reflection in chronic pulmonary thromboembolism and primary pulmonary hypertension. Journal of the American College of Cardiology. 2001;37(4):1085-1092
37.Rich S. Right ventricular adaptation and maladaptation in chronic pulmonary arterial hypertension. Cardiology Clinics. 2012;30(2):257-269
38.Van de Veerdonk MC, Kind T, Tim Marcus J, et al. Progressive right ventricular dysfunction in patients with pulmonary arterial hypertension responding to therapy. Journal of the American College of Cardiology. 2011;58(24):2511-2519
39.Stevens G, Garcia-Alvarez A, Sahni S, et al. RV dysfunction in pulmonary hypertension is independently related to pulmonary artery stiffness. JACC: Cardiovascular Imaging. 2012;5(4):378-387
40.Benza R, Gomberg-Maitland M, Greg Elliott C, et al. Predicting survival in patients with pulmonary arterial hypertension: The REVEAL risk score calculator 2.0 and comparison with ESC/ERS-based risk assessment strategies. Chest. 2019;156(2):323-337
41.Benza R, Kanwar M, Raina A, et al. Development and validation of an abridged version of the REVEAL 2.0 risk score calculator, REVEAL Lite 2, for use in patients with pulmonary arterial hypertension. Chest. 2021;159(1):337-346
42.Hoeper M, Pausch C, Olsson K, et al. COMPERA 2.0: A refined four-stratum risk assessment model for pulmonary arterial hypertension. The European Respiratory Journal. 2022;60(1):2102311
43.Humbert M, Farber H, Ghofrani H-A, et al. Risk assessment in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. The European Respiratory Journal. 2019;53(6):1802004
44.Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. The European Respiratory Journal. 2015;46:903-975
45.Sahay S, Tonelli A, Selej M, et al. Risk assessment in patients with functional class II pulmonary arterial hypertension: Comparison of physician gestalt with ESC/ERS and the REVEAL 2.0 risk score. PLoS One. 2020;15(11):e0241504
46.Sitbon O, Humbert M, Nunes H, et al. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: Prognostic factors and survival. Journal of the American College of Cardiology. 2002;40(4):780-788
47.Nickel N, Golpon H, Greer M, et al. The prognostic impact of follow-up assessments in patients with idiopathic pulmonary arterial hypertension. The European Respiratory Journal. 2012;39(3):589-596
48.Benza R, Miller D, Gomberg-Maitland M, et al. Predicting survival in pulmonary arterial hypertension: Insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management (REVEAL). Circulation. 2010;122(2):164-172
Written By
Aaron C. Miller
Submitted: 03 August 2023Reviewed: 19 August 2023Published: 05 December 2023
Open access peer-reviewed chapter - ONLINE FIRST
