Skip to main content

Main menu

  • Home
  • Current issue
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • COVID-19 submission information
    • Institutional open access agreements
    • Peer reviewer login
  • Alerts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • COVID-19 submission information
    • Institutional open access agreements
    • Peer reviewer login
  • Alerts
  • Subscriptions

Pulmonary hypertension: the importance of correctly diagnosing the cause

Sanjay Mehta, Jean-Luc Vachiéry
European Respiratory Review 2016 25: 372-380; DOI: 10.1183/16000617.0104-2016
Sanjay Mehta
1Southwest Ontario PH Clinic, London Health Sciences Centre, Victoria Hospital, Western University, London, ON, Canada
2Pulmonary Hypertension Association of Canada, Vancouver, BC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-Luc Vachiéry
3Pulmonary Vascular Diseases Clinic, Dept of Cardiology, Cliniques Universitaires de Bruxelles – Hôpital Erasme, Brussels, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: JeanLuc.Vachiery@erasme.ulb.ac.be
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Pulmonary hypertension (PH) is a complex condition that can occur as a result of a wide range of disorders, including left heart disease, lung disease and chronic pulmonary thromboembolism. Contemporary PH patients are older and frequently have a multitude of comorbidities that may contribute to or simply coincide with their PH. Identifying the cause of PH in these complicated patients can be challenging but is essential, given that the aetiology of the disease has a significant impact on the management options available. In this article, we present two cases that highlight the difficulties involved in obtaining a precise diagnosis of the cause of PH within the setting of multiple comorbidities. The importance of performing a comprehensive, multidimensional diagnostic work-up is demonstrated, in addition to the need to specifically consider cardiopulmonary haemodynamic data in the context of the wider clinical picture. The article also illustrates why achieving an accurate diagnosis is necessary for optimal patient management. This may involve treatment of comorbidities as a priority, which can ameliorate the severity of PH, obviating the need to consider PH-targeted medical treatment.

Abstract

Multidimensional testing in PH is essential, especially when patients present with comorbidities http://ow.ly/kYJa305OIi2

Introduction

An accurate and timely diagnosis of pulmonary hypertension (PH) and identification of the specific underlying cause of PH is essential to ensure that patients can be treated as early as possible with interventions that are appropriate for their diagnosis. Many effective PH-targeted therapies are available [1, 2] and when used in patients with appropriate types of PH, predominantly those with World Health Organization (WHO) Group 1 pulmonary arterial hypertension (PAH), these therapies can lead to significant improvements in functional capacity, quality of life and outcome [1, 2]. As the underlying cause and recommended management approach varies between patients, PH-targeted therapies are not suitable for all PH patients [1, 2]. For example, PH-targeted pharmacotherapies have not been shown to be effective for WHO Group 2 PH (PH due to left heart disease (LHD)) or WHO Group 3 PH (PH due to lung disease and/or hypoxia) [3].

As the appropriate treatment differs between PH patients [1, 2], it is important to correctly identify the cause of PH in each patient. However, obtaining a definitive diagnosis can be difficult due to the increasing age of PH patient populations and the fact that these patients frequently present with significant comorbidities, such as obesity, systemic hypertension, diabetes and underlying respiratory disorders [4, 5]. This article highlights the challenges associated with identifying the specific cause of PH in patients with significant comorbidities, and the importance of careful integration and interpretation of various multidimensional diagnostic tests in order to achieve this. Two patient cases are presented to illustrate the complexity of making a specific diagnosis of the cause of PH and the importance of achieving an accurate diagnosis in order to appropriately manage the disease.

Case 1

A 57-year-old male with newly identified PH was referred for assessment and treatment by the specialist PH clinic. He complained of a 1-year history of dyspnoea after walking up less than one flight of stairs, fatigue and ankle oedema, but no chest pain or orthopnoea. The patient had long-standing morbid obesity (body mass index (BMI) ∼55 kg·m−2), type 2 diabetes mellitus, systemic hypertension and obstructive sleep apnoea syndrome, and had previously been treated for atrial flutter. At the time of assessment, he was treated with two antihypertensive drugs, an antiarrhythmic drug and a diuretic. As shown in table 1, echocardiography indicated a high probability of PH and a normal left ventricular ejection fraction. Pulmonary function tests (PFTs) and blood gas analysis revealed no sign of lung disease. Pulmonary emboli were excluded by nuclear ventilation/perfusion (V′/Q′) lung scanning. Functional capacity was maintained, as shown by the 6-min walking distance (table 1). PH was confirmed by right heart catheterisation (RHC) (table 1). Although the pulmonary artery wedge pressure (PAWP) was close to the cut-off point of ≤15 mmHg commonly accepted to identify pre-capillary pulmonary hypertension (which includes PAH), as opposed to post-capillary pulmonary hypertension (which includes PH-LHD) [1, 2], it was considered unreliable due to the patient's obesity. Therefore, left heart catheterisation (LHC) was performed, which demonstrated an elevated left ventricular end-diastolic pressure (LVEDP) and an elevated diastolic pressure gradient (DPG = diastolic pulmonary arterial pressure (PAP) – LVEDP). This led to a final diagnosis of combined post- and pre-capillary pulmonary hypertension (Cpc-PH) (figure 1), in the context of heart failure with preserved ejection fraction (HFpEF) and obesity. The patient's obesity was subsequently treated successfully by bariatric surgery, which considerably improved his PH.

View this table:
  • View inline
  • View popup
TABLE 1

Cardiopulmonary and physiological parameters in case 1 at assessment

FIGURE 1
  • Download figure
  • Open in new tab
  • Download powerpoint
FIGURE 1

Pulmonary artery catheterisation haemodynamic tracings for case 1. a) The increase in pulmonary arterial pressure (PAP) is associated with an increase in the gradient between pulmonary artery diastolic pressure and pulmonary arterial wedge pressure (PAWP) to 25 mmHg. b) Marked respiratory variation in PAWP was observed. RAP: right atrial pressure.

Case 2

A 37-year-old female was referred to the specialist PH clinic with severe PH and right ventricular (RV) failure. She had recently been admitted to hospital with fatigue, dyspnoea and severe oedema, which had worsened over a period of 6 months. She was a former smoker of half a pack of cigarettes per day for 15 years but had no other history of cardiac or respiratory disease and no personal or family history of thromboembolism. On examination, she had severe kyphoscoliosis, moderate–severe peripheral oedema, marked jugular venous pressure elevation and evidence of PH. Echocardiography confirmed severe PH with no evidence of underlying LHD or right–left shunt on contrast bubble study (table 2). Measurement of arterial blood gases revealed chronic, compensated respiratory acidosis and marked hypoxaemia. PFTs indicated mild restrictive lung disease. Nuclear V′/Q′ lung scanning demonstrated ventilation heterogeneity due to kyphoscoliosis, with matched small, multifocal nonsegmental perfusion defects, not suggestive of chronic pulmonary emboli. An overnight polysomnogram revealed hypoventilation with rising arterial carbon dioxide tension (PaCO2) levels and marked hypoxaemia, but no central or obstructive apnoea events. She was diagnosed with chronic respiratory failure due to kyphoscoliosis, exacerbated by nocturnal hypoventilation, and resulting in significant chronic hypoxaemia and severe pre-capillary PH, most likely WHO Group 3 PH due to lung disease and/or hypoxia. She was initiated on continuous noninvasive face-mask ventilation, supplemental oxygen and diuretics. After 2 weeks in hospital, she was transitioned to home and continued on nocturnal noninvasive ventilation. 6 months later, she was markedly improved clinically and had achieved near-normal daytime PaCO2 levels with resolution of hypoxaemia, as well as marked improvement in her PH with no evidence of RV failure.

View this table:
  • View inline
  • View popup
TABLE 2

Cardiopulmonary and physiological parameters in case 2 at diagnosis and 6 months following initiation of chronic noninvasive ventilation

Discussion

In this article, two cases have been selected to illustrate the complex and challenging approach to making an accurate diagnosis of the cause of PH and the importance of this to ensure appropriate management. The main points that will be considered are: first, multiple potential contributing illnesses and mechanisms should be considered before making a specific diagnosis of the cause of PH; second, comorbidities can complicate the specific diagnosis of PH; third, a multifactorial diagnostic work-up is necessary to correctly determine PH aetiology; and fourth, accurate diagnosis is essential to ensure appropriate management.

Multiple potential causes of PH to consider when making a specific diagnosis of PH

A number of diverse conditions can cause PH and this is illustrated by the clinical classification, which categorises PH into five distinct groups: WHO Group 1 (PAH), WHO Group 2 (PH-LHD), WHO Group 3 (PH due to lung disease and/or hypoxia), WHO Group 4 (chronic thromboembolic pulmonary hypertension (CTEPH) and other pulmonary artery obstructions) and WHO Group 5 (PH with unclear or multifactorial mechanisms) [1, 2]. Before reaching any specific PH diagnosis in an individual patient, clinicians should consider all potential comorbid conditions that can lead to the development of PH [1, 2].

Obesity is an independent risk factor for PH [6, 7] and may directly contribute to the development of PH [8]. Indeed, it has been estimated that up to 5% of otherwise healthy individuals with a BMI >30 kg·m−2 have moderate or severe PH [8]. The mechanism by which PH occurs in obese patients may simply be due to the fact that obese patients are at increased risk of other conditions that can cause PH, including LHD, pulmonary thromboembolism and sleep-disordered breathing [8]. Obesity is particularly common in the USA, Canada and the UK [9–11], and is expected to become more frequent in other developed [9] and developing [11] countries. Therefore, it is clear that in the coming years, specialist PH centres will be seeing more obese patients with PH, like the patient illustrated in case 1.

Several types of lung diseases can lead to pre-capillary PH (WHO Group 3 PH due to lung disease and/or hypoxia) [1, 2]. Sleep-disordered breathing is one example, and can include obstructive sleep apnoea and nocturnal hypoventilation, which can be related to obesity [8, 12]. Sleep-disordered breathing is very common in obese patients, and screening for sleep disorders should be part of a routine work-up in obese patients with PH [13]. Hypoventilation both during daytime and nocturnally can also arise due to skeletal deformities such as kyphoscoliosis, as illustrated by case 2. Kyphoscoliosis is an abnormal curvature of the spine in both the anterior and lateral directions, which results in reduced chest wall compliance [14]. As such, respiratory difficulties are common in patients with significant kyphoscoliosis and chronic respiratory failure can develop [14]. PH is a common complication of severe kyphoscoliosis, developing as a result of hypoxaemia due to hypoventilation, and to a lesser extent, hypercapnia [14]. PH is also common in patients with chronic advanced lung diseases, including pulmonary fibrosis and chronic obstructive pulmonary disease, especially when both conditions are present [15]. Comorbid PH and chronic lung disease is associated with increased mortality and reduced functional status, as well as quality of life, highlighting the clinical need to accurately and completely diagnose all respiratory conditions in patients suspected of having PH [16, 17].

CTEPH is an important cause of pre-capillary PH [18]. Diagnosis of this form of PH is crucial, as it can often be cured by pulmonary endarterectomy (PEA) [1, 2, 18, 19], and can also be treated with PH-specific medications [1, 2, 18]. Patients with recurrent or multiple pulmonary emboli are at risk of CTEPH [20, 21], despite effective anticoagulation. It is recommended that specific diagnostic testing is conducted to investigate the presence of CTEPH in all patients being assessed for PH [1, 2, 18, 22].

PH is a common complication of LHD, including systolic and diastolic left ventricular (LV) dysfunction and left-sided valvular disease, although the exact prevalence of PH among patients with LHD is unknown [23–26]. PH-LHD is caused by passive backward transmission of elevated filling pressures (i.e. LVEDP), and is associated with more severe symptoms, worse exercise capacity and a negative impact on clinical outcomes [23]. There are no approved therapies for PH-LHD [23]; studies have not established any benefit of PH-specific medications in patients with PH-LHD, and conversely, have reported significant adverse effects [1–3]. As a result, distinguishing PH-LHD from PAH is essential but this can be challenging [23, 27], particularly when PH is due to occult LHD (such as HFpEF as seen in case 1). One factor that contributes to the challenge of differentiating between PH-LHD and PAH is the changing demographics of PAH populations. Historically, PH-LHD patients were considered as being typically older than PAH patients [1, 2]; today, PAH populations have a higher mean age than those in the past [28]. As the age of PAH patients increases, the likelihood of confusing PH-LHD with PAH also becomes higher. In part due to their increasing age, PAH patients today also have more comorbidities than in the past [4, 29]. Indeed, recent registry data indicate that a significant proportion of PAH patients now have a comorbidity profile similar to that found in PH-LHD patients, including obesity, diabetes and atrial fibrillation. Case 1 provides an example of a patient with PH-LHD due to HFpEF with exactly such a comorbidity profile: he was morbidly obese and had been previously diagnosed with a number of chronic conditions, including type 2 diabetes mellitus and systemic hypertension. In these patients, it is important to carefully define the haemodynamic profile, using LHC in cases of uncertainty, to clearly distinguish between a diagnosis of PAH or PH-LHD.

Multifactorial diagnostic assessment of patients with suspected PH

Given the multiple potential causes of PH and the impact that the specific PH diagnosis can have on the most appropriate treatment, clinicians should perform a comprehensive multifactorial work-up to correctly determine the precise cause of PH.

Once PH is suspected, echocardiography is recommended to assess heart structure and function, and to determine the probability of PH [1, 2]. In case 1, echocardiography revealed a tricuspid valve regurgitation velocity that was above the upper limit of normal of 3.4 m·s−1 recommended in the European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines [1, 2], and which indicates a high probability of PH. Furthermore, elevated right ventricular systolic pressure is an important clue to the presence of clinically significant PH. In some cases, a structural left heart abnormality can be detected by echocardiography, raising suspicion of PH-LHD [1, 2]. However, echocardiographic parameters suggestive of PH-LHD are not easily measurable in all patients with LHD [25]. In particular, echocardiographic findings of HFpEF are often subtle and can easily be missed [26]. This was observed in the patient in case 1; although he was ultimately diagnosed with LHD, he had no obvious echocardiographic left-sided cardiac abnormalities, and both left ventricular ejection fraction and left atrial size were normal. In patients with obesity, good quality echocardiographic images can be difficult to obtain, and this was observed for case 1. Indeed, echocardiographic images are classified as being “nondiagnostic” in up to 30% of obese patients [30, 31].

Rigorous evaluation of the potential contribution of significant lung disease is indicated during diagnostic work-up. PFTs should be conducted to provide a specific assessment of lung function and to establish important obstructive or restrictive lung disease. Indeed, for the patient in case 2, PFTs indicated moderate restrictive lung disease, which helped to reach the final diagnosis of WHO Group 3 PH due to lung disease and/or hypoxia. Measurement of arterial blood gases established the presence of resting hypoxaemia, which was also essential in order to support this cause of PH. Moreover, the presence of daytime or nocturnal elevated PaCO2 levels confirms hypoventilation, which is an important risk factor for WHO Group 3 PH [1, 2].

Thoracic computed tomography (CT) imaging is a valuable tool in the diagnostic approach to PH [1, 2]. CT findings can suggest the presence of PH, including main or hilar pulmonary artery enlargement, RV enlargement, or reflux of contrast material into the inferior vena cava or hepatic veins, and can also indicate the presence of significant underlying lung disease as a cause of PH [1, 2]. In case 1, a contrast-enhanced thoracic CT scan showed relatively small lungs (possibly due to the patient's morbid obesity) and large hilar pulmonary arteries but no evidence of parenchymal lung disease.

It is strongly recommended that in all patients with PH, the potential contribution of chronic pulmonary emboli should be examined using a V′/Q′ lung scan [1, 2, 18]. Mismatched segmental perfusion defects indicate the possibility of CTEPH [1, 2], whereas a normal or low-probability V′/Q′ scan allows CTEPH to be excluded, as in both cases presented.

Identifying the underlying cause of PH can be aided by performing exercise testing. Exercise testing with a 6-min walk test objectively assesses functional capacity in PH patients, confirming clinical severity of symptoms and exercise limitation, but does not provide any information regarding the specific cause of PH. Moreover, 6-min walk distance values both at baseline and during follow-up can predict the risk of death in many types of PH [32, 33]. As such, clinical practice guidelines recommend baseline and serial assessment of exercise capacity with a 6-min walk test [1, 2]. More information can be provided by cardiopulmonary exercise testing (CPET), which is becoming increasingly utilised in clinical practice, and is now considered the gold standard test for evaluating the causes of dyspnoea and exercise intolerance [34, 35]. CPET can be particularly useful in the differential diagnosis of PH as the pattern of cardiopulmonary and gas-exchange responses can distinguish between pulmonary and cardiac limitations to exercise [35]. It must be cautioned that the proper performance and accurate interpretation of CPET in patients with PH requires significant technical and scientific expertise, as well as critical monitoring of patients in order to ensure safety.

The role of heart catheterisation in PH diagnosis

In order to definitively diagnose the cause of PH, guidelines recommend that RHC should be performed [1, 2]. This is particularly critical for the diagnosis of pre-capillary forms of PH, such as PAH, that can be treated with PH-specific medications. Despite the guideline recommendations, some patients are diagnosed with PH and treated with PH-specific medications without undergoing RHC as part of their assessment [36], and this can lead to inaccurate diagnoses and adverse outcomes [37]. One reason for not performing RHC may include concerns regarding the safety of the procedure [38] as cardiorespiratory, hypotensive or device-related complications can occur [39, 40]. Despite these concerns, RHC is considered to be safe at expert centres, with low morbidity and mortality rates of 1.1% and 0.055%, respectively [39]. Underuse of RHC may also be due to a lack of technical training or knowledge. The complexities of the technique, along with a lack of standardisation, can make RHC vulnerable to technical or data interpretation errors [40, 41]. To address this, guidance on optimising RHC is available and provided in table 3. Additional practical recommendations related to the specific measurement or derivation of certain haemodynamic variables have also recently been published [40]. Adoption of a standardised protocol for RHC, as well as ensuring that staff are appropriately trained, can improve the accuracy of RHC measurements and, therefore, of PH diagnosis [1, 2, 29, 40–45].

View this table:
  • View inline
  • View popup
TABLE 3

Potential sources of error when performing right heart catheterisation and guidance on how to minimise the impact of these errors

By RHC, PH is defined as a mean PAP ≥25 mmHg, and can be further differentiated into pre-capillary PH and post-capillary PH on the basis of the PAWP, such that PAWP ≤15 mmHg defines pre-capillary PH and PAWP >15 mmHg indicates post-capillary PH [1, 2]. Post-capillary PH can exist in an isolated form or as Cpc-PH [1, 2]. The haemodynamic distinction of the latter type is made based on PH in the presence of PAWP >15 mmHg, as well as findings of an elevated pulmonary vascular resistance (>3 Wood units) and/or an increased DPG (PAPdiastolic − PAWP ≥7 mmHg) [1, 2]. In patients with post-capillary PH, the additional pre-capillary component can be due to underlying lung disease [1, 2] or as a result of a pulmonary vascular remodelling process in the setting of chronic LHD, as in mitral stenosis, LV systolic dysfunction or HFpEF [23–25]. In case 1, RHC revealed the presence of significant PH (table 1), with elevated PAP (normal mean PAP ≤20 mmHg [1, 2, 29]) and increased pulmonary vascular resistance (normal ≤1.5 Wood units [46, 47]). In addition, a PAWP of 16 mmHg was measured (figure 1a), which is close to the cut-off point of ≤15 mmHg described above [1, 2]. However, because of the obesity, there were marked respiratory swings in the RHC trace which can affect the accuracy of the PAWP reading (figure 1b). If the PAWP value is unreliable or if there are significant risk factors for LHD (both of which occurred in case 1), the current ESC/ERS guidelines state that LHC should be considered to directly measure LVEDP [1, 2]. LVEDP is the gold standard measurement for distinguishing between pre- and post-capillary PH. In contrast, PAWP is only an estimate and can be affected by many factors, including respiratory swings [40]. The LHC results in case 1 revealed an elevated DPG. The degree of elevation of mean PAP in this patient could not be explained entirely by the PAWP and LVEDP values, suggesting the presence of a pre-capillary component to this patient's PH. Therefore, the most appropriate diagnosis for the patient in case 1 was WHO Group 2 PH-LHD with Cpc-PH, complicated by morbid obesity. The post-capillary component was a result of HFpEF. The pre-capillary component was likely the result of pulmonary vascular remodelling in the setting of HFpEF.

Invasive measurement of cardiopulmonary haemodynamics during exercise rather than at rest as described above may provide additional diagnostic value. Patients with HFpEF in the early stages of the disease may have normal haemodynamic values at rest or may have haemodynamic values suggestive of PH (defined as high resting PAP, but with normal PAWP and/or LVEDP [≤15 mmHg]). However, when the cardiovascular system is stressed and cardiac output increases during exercise, pathological changes in systolic PAP, mean PAP and PAWP may occur [48]. Haemodynamic testing during exercise can therefore “unmask” diastolic dysfunction, aiding the early diagnosis of HFpEF [49]. Exercise haemodynamics are especially useful in obese patients [49] who, as seen in case 1, often present with unreliable PAWP values. As invasive exercise testing is not universally available, fluid loading can be used as an alternative method of stressing the cardiovascular system, although it may be less sensitive than exercise testing [48]. Currently, the methodology of haemodynamic exercise testing in the diagnosis of PH is not standardised and guidelines do not recommend it as a routine diagnostic test [1, 2, 49]. A recent publication has suggested a diagnostic algorithm for interpreting the haemodynamic and ventilatory data that CPET with invasive haemodynamic assessment provides [50], which may help to standardise this technique in the future.

To identify the correct cause of PH, particularly in the setting of patients who have multiple comorbidities, a comprehensive, multidimensional diagnostic methodology is required, as illustrated by the two cases presented. Due to the increasing complexity of diagnosing PH, it is recommended that patients presenting with suspected PH are referred to a specialist PH centre [15]. Furthermore, clinicians working outside of these centres are encouraged to discuss complex cases with PH specialists to aid a timely and accurate diagnosis.

The implications of PH diagnosis on patient management

Failure to reach a correct diagnosis of the cause of PH in an individual patient can result in patients receiving inappropriate treatments for their specific type of PH. PH-targeted medications are approved and effective in patients with PAH [1, 2], but are not indicated for many of the other forms of PH.

For patients with PH-LHD, PH-specific therapies are not recommended or approved [1–3] as they have demonstrated a lack of efficacy in patients with HFpEF and those with PH due to systolic LV dysfunction [51–54]. Moreover, in patients with heart failure and a reduced ejection fraction, PH-specific therapies have increased the occurrence of adverse events [55] or hastened disease progression as a consequence of fluid retention [56]. Similarly, the use of drugs approved for PH is not recommended in patients with PH due to lung diseases [1, 2]. This highlights the critical importance of differentiating PAH from WHO Group 2 PH-LHD or WHO Group 3 PH due to lung disease and/or hypoxia prior to initiating PH-targeted medical therapy. The optimal management of CTEPH patients is different again to that of other forms of PH, with surgical PEA being the treatment of choice in eligible patients [1, 2]. Medical treatment of CTEPH patients with PH-targeted therapy may be justified for inoperable patients or for patients with persistent or recurrent PH following PEA [1, 2].

For the management of PH in WHO Groups 2 and 3, treatment of the underlying cause/comorbidity is essential and is recommended in the ESC/ERS guidelines for PH [1, 2]. Treatment of comorbidities in PH patients is important as it has been demonstrated that certain comorbidities are associated with worse outcomes in patients with PH. For example, long-term survival appears worse in PH patients with diabetes in comparison to PH patients without diabetes [57]. Furthermore, a recent meta-analysis has demonstrated that bariatric surgery leads to short-term clinical improvements in PH in obese patients [58]. In alignment with this, in case 1, the patient underwent a sleeve gastric band procedure, which led to significant improvements in his condition. 2 years after surgery, the patient's BMI had reduced to 36.6 kg·m−2. Follow-up echocardiography indicated that he was largely cured of his PH. There was a qualitative improvement in RV size/left ventricle compression and right atrium size. Treatment of underlying chronic hypoventilation due to kyphoscoliosis using noninvasive ventilation also markedly improved PH in case 2. This is in line with previous data on the treatment of chronic hypoventilation syndromes using ventilation therapy. In a retrospective analysis that assessed patients with daytime PH due to hypoventilation, noninvasive ventilation was found to significantly improve haemodynamics and exercise capacity [59].

In addition to highlighting the benefits of treating comorbidities, case 1 also illustrates how failure to reach a definitive diagnosis can have significant implications for the management of PH patients. Undiagnosed conditions can result in patients being rejected for potentially beneficial procedures. The patient in case 1 had previously been refused bariatric surgery, as there was a perceived risk of operating in the setting of an unidentified cardiopulmonary condition. Following successful diagnosis of PH, and discussions between specialist surgical and cardiology staff, the original decision not to operate was overturned as surgeons felt that the PH was reversible.

Conclusion

As illustrated in this review, the accurate diagnosis of the underlying cause of PH is associated with a number of challenges. There are multiple cardiac and pulmonary conditions that can contribute to the development of PH, and the frequency and variety of comorbid conditions complicates the diagnostic approach to a PH patient. It is, however, essential that the type of PH is correctly identified, in order to ensure that patients are optimally managed.

Disclosures

Supplementary Material

S. Mehta ERR-0104-2016_Mehta

J-L. Vachiery ERR-0104-2016_Vachiery

Acknowledgements

We would like to thank James Glasper (nspm Ltd, Meggen, Switzerland) for medical writing assistance, funded by Actelion Pharmaceuticals Ltd (Allschwil, Switzerland).

Footnotes

  • Editorial comment in Eur Respir Rev 2016; 25: 361–363.

  • Conflict of interest: Disclosures can be found alongside this article at err.ersjournals.com

  • Provenance: The European Respiratory Review received sponsorship from Actelion Pharmaceuticals Ltd, Allschwil, Switzerland, for the publication of these peer-reviewed articles.

  • Received August 19, 2016.
  • Accepted October 18, 2016.
  • Copyright ©ERS 2016.

ERR articles are open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

References

  1. ↵
    1. Galiè N,
    2. Humbert M,
    3. Vachiery JL, et al.
    2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J 2016; 37: 67–119.
    OpenUrlFREE Full Text
  2. ↵
    1. Galiè N,
    2. Humbert M,
    3. Vachiery JL, et al.
    2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 2015; 46: 903–975.
    OpenUrlAbstract/FREE Full Text
  3. ↵
    1. Farber HW,
    2. Gibbs S
    . Under pressure: pulmonary hypertension associated with left heart disease. Eur Respir Rev 2015; 24: 665–673.
    OpenUrlAbstract/FREE Full Text
  4. ↵
    1. Ling Y,
    2. Johnson MK,
    3. Kiely DG, et al.
    Changing demographics, epidemiology, and survival of incident pulmonary arterial hypertension: results from the pulmonary hypertension registry of the United Kingdom and Ireland. Am J Respir Crit Care Med 2012; 186: 790–796.
    OpenUrlCrossRefPubMed
  5. ↵
    1. Hoeper MM,
    2. Simon RGJ
    . The changing landscape of pulmonary arterial hypertension and implications for patient care. Eur Respir Rev 2014; 23: 450–457.
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Leung CC,
    2. Moondra V,
    3. Catherwood E, et al.
    Prevalence and risk factors of pulmonary hypertension in patients with elevated pulmonary venous pressure and preserved ejection fraction. Am J Cardiol 2010; 106: 284–286.
    OpenUrlCrossRefPubMed
  7. ↵
    1. Choudhary G,
    2. Jankowich M,
    3. Wu WC
    . Prevalence and clinical characteristics associated with pulmonary hypertension in African-Americans. PLoS One 2013; 8: e84264.
    OpenUrlCrossRefPubMed
  8. ↵
    1. Friedman SE,
    2. Andrus BW
    . Obesity and pulmonary hypertension: a review of pathophysiologic mechanisms. J Obes 2012; 2012: 505274.
    OpenUrlPubMed
  9. ↵
    1. Twells LK,
    2. Gregory DM,
    3. Reddigan J, et al.
    Current and predicted prevalence of obesity in Canada: a trend analysis. CMAJ Open 2014; 2: E18–E26.
    OpenUrl
    1. Ogden CL,
    2. Carroll MD,
    3. Fryar CD, et al.
    Prevalence of obesity among adults and youth: United States, 2011–2014. NCHS Data Brief 2015; 1–8.
  10. ↵
    1. Ng M,
    2. Fleming T,
    3. Robinson M, et al.
    Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014; 384: 766–781.
    OpenUrlCrossRefPubMed
  11. ↵
    1. Arias MA,
    2. Garcia-Rio F,
    3. Alonso-Fernandez A, et al.
    Pulmonary hypertension in obstructive sleep apnoea: effects of continuous positive airway pressure: a randomized, controlled cross-over study. Eur Heart J 2006; 27: 1106–1113.
    OpenUrlAbstract/FREE Full Text
  12. ↵
    1. Kholdani C,
    2. Fares WH,
    3. Mohsenin V
    . Pulmonary hypertension in obstructive sleep apnea: is it clinically significant? A critical analysis of the association and pathophysiology. Pulm Circ 2015; 5: 220–227.
    OpenUrl
  13. ↵
    1. Weinberger SE,
    2. Cockrill BA,
    3. Mandel J
    . Principles of Pulmonary Medicine. 5th Edn. Saunders Elsevier, 2008.
  14. ↵
    1. Seeger W,
    2. Adir Y,
    3. Barbera JA
    . Pulmonary hypertension in chronic lung diseases. J Am Coll Cardiol 2013; 62: D109–D116.
    OpenUrlFREE Full Text
  15. ↵
    1. Hayes D Jr.,
    2. Black SM,
    3. Tobias JD, et al.
    Influence of pulmonary hypertension on survival in advanced lung disease. Lung 2015; 193: 213–221.
    OpenUrl
  16. ↵
    1. Cuttica MJ
    . Pulmonary hypertension associated with lung diseases and hypoxemia. Heart Fail Rev 2016; 21: 299–308.
    OpenUrl
  17. ↵
    1. Mehta S,
    2. Helmersen D,
    3. Provencher S, et al.
    Diagnostic evaluation and management of chronic thromboembolic pulmonary hypertension: a clinical practice guideline. Can Respir J 2010; 17: 301–334.
    OpenUrlCrossRefPubMed
  18. ↵
    1. McNeil K,
    2. Dunning J
    . Chronic thromboembolic pulmonary hypertension (CTEPH). Heart 2007; 93: 1152–1158.
    OpenUrlFREE Full Text
  19. ↵
    1. Lang I
    . Chronic thromboembolic pulmonary hypertension: a distinct disease entity. Eur Respir Rev 2015; 24: 246–252.
    OpenUrlAbstract/FREE Full Text
  20. ↵
    1. Yang S,
    2. Yang Y,
    3. Zhai Z, et al.
    Incidence and risk factors of chronic thromboembolic pulmonary hypertension in patients after acute pulmonary embolism. J Thorac Dis 2015; 7: 1927–1938.
    OpenUrl
  21. ↵
    1. Lang IM,
    2. Madani M
    . Update on chronic thromboembolic pulmonary hypertension. Circulation 2014; 130: 508–518.
    OpenUrlFREE Full Text
  22. ↵
    1. Vachiéry JL,
    2. Adir Y,
    3. Barbera JA
    . Pulmonary hypertension due to left heart diseases. J Am Coll Cardiol 2013; 62: D100–D108.
    OpenUrlFREE Full Text
    1. Guazzi M,
    2. Borlaug BA
    . Pulmonary hypertension due to left heart disease. Circulation 2012; 126: 975–990.
    OpenUrlFREE Full Text
  23. ↵
    1. Guazzi M,
    2. Galie N
    . Pulmonary hypertension in left heart disease. Eur Respir Rev 2012; 21: 338–346.
    OpenUrlAbstract/FREE Full Text
  24. ↵
    1. Hansdottir S,
    2. Groskreutz DJ,
    3. Gehlbach BK
    . WHO's in second? A practical review of World Health Organization group 2 pulmonary hypertension. Chest 2013; 144: 638–650.
    OpenUrlCrossRefPubMed
  25. ↵
    1. Rosenkranz S,
    2. Gibbs JS,
    3. Wachter R, et al.
    Left ventricular heart failure and pulmonary hypertension. Eur Heart J 2016; 37: 942–954.
    OpenUrlAbstract/FREE Full Text
  26. ↵
    1. McGoon MD,
    2. Miller DP
    . REVEAL: a contemporary US pulmonary arterial hypertension registry. Eur Respir Rev 2012; 21: 8–18.
    OpenUrlFREE Full Text
  27. ↵
    1. Hoeper MM,
    2. Bogaard HJ,
    3. Condliffe R
    . Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol 2013; 62: D42–D50.
    OpenUrlFREE Full Text
  28. ↵
    1. Murphy M,
    2. Krothapalli S,
    3. Cuellar J, et al.
    Prognostic value of normal stress echocardiography in obese patients. J Obes 2014; 2014: 419724.
    OpenUrl
  29. ↵
    1. Mulvagh SL,
    2. DeMaria AN,
    3. Feinstein SB, et al.
    Contrast echocardiography: current and future applications. J Am Soc Echocardiogr 2000; 13: 331–342.
    OpenUrlCrossRefPubMed
  30. ↵
    1. Humbert M,
    2. Sitbon O,
    3. Chaouat A, et al.
    Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 2010; 122: 156–163.
    OpenUrlAbstract/FREE Full Text
  31. ↵
    1. Farber HW,
    2. Miller DP,
    3. McGoon MD, et al.
    Predicting outcomes in pulmonary arterial hypertension based on the 6-minute walk distance. J Heart Lung Transplant 2015; 34: 362–368.
    OpenUrlCrossRefPubMed
  32. ↵
    1. Ferrazza AM,
    2. Martolini D,
    3. Valli G, et al.
    Cardiopulmonary exercise testing in the functional and prognostic evaluation of patients with pulmonary diseases. Respiration 2009; 77: 3–17.
    OpenUrlCrossRefPubMed
  33. ↵
    1. Palange P,
    2. Ward SA,
    3. Carlsen KH, et al.
    Recommendations on the use of exercise testing in clinical practice. Eur Respir J 2007; 29: 185–209.
    OpenUrlAbstract/FREE Full Text
  34. ↵
    1. McLaughlin VV,
    2. Langer A,
    3. Tan M, et al.
    Contemporary trends in the diagnosis and management of pulmonary arterial hypertension: an initiative to close the care gap. Chest 2013; 143: 324–332.
    OpenUrlCrossRefPubMed
  35. ↵
    1. Deano RC,
    2. Glassner-Kolmin C,
    3. Rubenfire M, et al.
    Referral of patients with pulmonary hypertension diagnoses to tertiary pulmonary hypertension centers: the multicenter RePHerral study. JAMA Intern Med 2013; 173: 887–893.
    OpenUrlCrossRefPubMed
  36. ↵
    1. Zuckerman WA,
    2. Turner ME,
    3. Kerstein J, et al.
    Safety of cardiac catheterization at a center specializing in the care of patients with pulmonary arterial hypertension. Pulm Circ 2013; 3: 831–839.
    OpenUrlCrossRefPubMed
  37. ↵
    1. Hoeper MM,
    2. Lee SH,
    3. Voswinckel R, et al.
    Complications of right heart catheterization procedures in patients with pulmonary hypertension in experienced centers. J Am Coll Cardiol 2006; 48: 2546–2552.
    OpenUrlFREE Full Text
  38. ↵
    1. Rosenkranz S,
    2. Preston IR
    . Right heart catheterisation: best practice and pitfalls in pulmonary hypertension. Eur Respir Rev 2015; 24: 642–652.
    OpenUrlAbstract/FREE Full Text
  39. ↵
    1. Mathier M
    . The nuts and bolts of interpreting hemodynamics in pulmonary hypertension associated with diastolic heart failure. Adv Pulm Hypertens J 2011; 10: 33–40.
    OpenUrl
    1. Tonelli AR,
    2. Mubarak KK,
    3. Li N, et al.
    Effect of balloon inflation volume on pulmonary artery occlusion pressure in patients with and without pulmonary hypertension. Chest 2011; 139: 115–121.
    OpenUrlCrossRefPubMed
    1. LeVarge BL,
    2. Pomerantsev E,
    3. Channick RN
    . Reliance on end-expiratory wedge pressure misclassifies pulmonary hypertension. Eur Respir J 2014; 44: 425–434.
    OpenUrlAbstract/FREE Full Text
    1. Kovacs G,
    2. Avian A,
    3. Pienn M, et al.
    Reading pulmonary vascular pressure tracings. How to handle the problems of zero leveling and respiratory swings. Am J Respir Crit Care Med 2014; 190: 252–257.
    OpenUrlPubMed
  40. ↵
    1. Kovacs G,
    2. Avian A,
    3. Olschewski A, et al.
    Zero reference level for right heart catheterisation. Eur Respir J 2013; 42: 1586–1594.
    OpenUrlAbstract/FREE Full Text
  41. ↵
    1. Kovacs G,
    2. Berghold A,
    3. Scheidl S, et al.
    Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J 2009; 34: 888–894.
    OpenUrlAbstract/FREE Full Text
  42. ↵
    1. Baim DS, ed.
    Grossman's Cardiac Catheterization, Angiography, and Intervention. 7th Edn. Philadelphia, Lippincott Williams & Wilkins, 2006.
  43. ↵
    1. Andersen MJ,
    2. Olson TP,
    3. Melenovsky V, et al.
    Differential hemodynamic effects of exercise and volume expansion in people with and without heart failure. Circ Heart Fail 2015; 8: 41–48.
    OpenUrlAbstract/FREE Full Text
  44. ↵
    1. Maor E,
    2. Grossman Y,
    3. Balmor RG, et al.
    Exercise haemodynamics may unmask the diagnosis of diastolic dysfunction among patients with pulmonary hypertension. Eur J Heart Fail 2015; 17: 151–158.
    OpenUrlCrossRefPubMed
  45. ↵
    1. Berry NC,
    2. Manyoo A,
    3. Oldham WM, et al.
    Protocol for exercise hemodynamic assessment: Performing an invasive cardiopulmonary exercise test in clinical practice. Pulm Circ 2015; 5: 610–618.
    OpenUrl
  46. ↵
    1. Hoendermis ES,
    2. Liu LC,
    3. Hummel YM, et al.
    Effects of sildenafil on invasive haemodynamics and exercise capacity in heart failure patients with preserved ejection fraction and pulmonary hypertension: a randomized controlled trial. Eur Heart J 2015; 36: 2565–2573.
    OpenUrlAbstract/FREE Full Text
    1. Borlaug BA,
    2. Lewis GD,
    3. McNulty SE, et al.
    Effects of sildenafil on ventricular and vascular function in heart failure with preserved ejection fraction. Circ Heart Fail 2015; 8: 533–541.
    OpenUrlAbstract/FREE Full Text
    1. Redfield MM,
    2. Chen HH,
    3. Borlaug BA, et al.
    Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA 2013; 309: 1268–1277.
    OpenUrlCrossRefPubMed
  47. ↵
    1. Bonderman D,
    2. Ghio S,
    3. Felix SB, et al.
    Riociguat for patients with pulmonary hypertension caused by systolic left ventricular dysfunction: a phase IIb double-blind, randomized, placebo-controlled, dose-ranging hemodynamic study. Circulation 2013; 128: 502–511.
    OpenUrlAbstract/FREE Full Text
  48. ↵
    1. Packer M,
    2. McMurray J,
    3. Massie BM, et al.
    Clinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: results of a pilot study. J Card Fail 2005; 11: 12–20.
    OpenUrlCrossRefPubMed
  49. ↵
    1. Kalra PR,
    2. Moon JC,
    3. Coats AJ
    . Do results of the ENABLE (Endothelin Antagonist Bosentan for Lowering Cardiac Events in Heart Failure) study spell the end for non-selective endothelin antagonism in heart failure? Int J Cardiol 2002; 85: 195–197.
    OpenUrlCrossRefPubMed
  50. ↵
    1. Abernethy AD,
    2. Stackhouse K,
    3. Hart S, et al.
    Impact of diabetes in patients with pulmonary hypertension. Pulm Circ 2015; 5: 117–123.
    OpenUrl
  51. ↵
    1. Sheu EG,
    2. Channick R,
    3. Gee DW
    . Improvement in severe pulmonary hypertension in obese patients after laparoscopic gastric bypass or sleeve gastrectomy. Surg Endosc 2016; 30: 633–637.
    OpenUrl
  52. ↵
    1. Held M,
    2. Walthelm J,
    3. Baron S, et al.
    Functional impact of pulmonary hypertension due to hypoventilation and changes under noninvasive ventilation. Eur Respir J 2014; 43: 156–165.
    OpenUrlAbstract/FREE Full Text
PreviousNext
Back to top
View this article with LENS
Vol 25 Issue 142 Table of Contents
European Respiratory Review: 25 (142)
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
Email

Thank you for your interest in spreading the word on European Respiratory Society .

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Pulmonary hypertension: the importance of correctly diagnosing the cause
(Your Name) has sent you a message from European Respiratory Society
(Your Name) thought you would like to see the European Respiratory Society web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
Citation Tools
Pulmonary hypertension: the importance of correctly diagnosing the cause
Sanjay Mehta, Jean-Luc Vachiéry
European Respiratory Review Dec 2016, 25 (142) 372-380; DOI: 10.1183/16000617.0104-2016

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Pulmonary hypertension: the importance of correctly diagnosing the cause
Sanjay Mehta, Jean-Luc Vachiéry
European Respiratory Review Dec 2016, 25 (142) 372-380; DOI: 10.1183/16000617.0104-2016
Reddit logo Technorati logo Twitter logo Connotea logo Facebook logo Mendeley logo
Full Text (PDF)

Jump To

  • Article
    • Abstract
    • Abstract
    • Introduction
    • Case 1
    • Case 2
    • Discussion
    • Conclusion
    • Disclosures
    • Acknowledgements
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Subjects

  • Pulmonary vascular disease
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

  • Protecting healthcare workers from SARS-COV-2 infections
  • Bronchiectasis: case-based investigation and management
  • A European regulatory perspective on cystic fibrosis
Show more Frontiers in Clinical Practice

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About the ERR

  • Journal information
  • Editorial board
  • Press
  • Permissions and reprints
  • Advertising
  • Sponsorship

The European Respiratory Society

  • Society home
  • myERS
  • Privacy policy
  • Accessibility

ERS publications

  • European Respiratory Journal
  • ERJ Open Research
  • European Respiratory Review
  • Breathe
  • ERS books online
  • ERS Bookshop

Help

  • Feedback

For authors

  • Instructions for authors
  • Publication ethics and malpractice
  • Submit a manuscript

For readers

  • Alerts
  • Subjects
  • RSS

Subscriptions

  • Accessing the ERS publications

Contact us

European Respiratory Society
442 Glossop Road
Sheffield S10 2PX
United Kingdom
Tel: +44 114 2672860
Email: journals@ersnet.org

ISSN

Print ISSN: 0905-9180
Online ISSN: 1600-0617

Copyright © 2023 by the European Respiratory Society