Medical Journal of Dr. D.Y. Patil Vidyapeeth

REVIEW ARTICLE
Year
: 2021  |  Volume : 14  |  Issue : 3  |  Page : 255--264

Pulmonary hypertension: A simplified pulmonologists' perspective


Ketaki Utpat, Unnati Desai, Kumar Doshi, Jyotsna M Joshi 
 Department of Pulmonary Medicine, TNMC and BYL Nair Hospital, Mumbai, Maharashtra, India

Correspondence Address:
Unnati Desai
Department of Pulmonary Medicine, 2nd Floor, OPD Building, TNMC and BYL Nair Hospital, AL Nair Road, Mumbai Central, Mumbai - 400 008, Maharashtra
India

Abstract

Pulmonary hypertension (PH) is a progressive disorder of the pulmonary vasculature caused due to vasoconstriction, vasodestruction, or vaso-obliteration. PH results from heterogeneous pathophysiologic mechanisms culminating in elevation of mean pulmonary arterial pressure. Patients may either present with symptoms or with chest radiographic, electrocardiographic, or echocardiographic findings done as a part of diagnostic evaluation for the primary disease or as a part of preoperative assessment. And hence, the clinician resorted to could be a family physician, pulmonologist, cardiologist, surgeon, or anesthesiologist. Hence, there is a necessity of a basic awareness about its clinical presentations, diagnostic modalities, and the available treatment options. The diagnosis can be perplexing and warrants a stepwise evaluation. Echocardiography (ECHO) is the preliminary diagnostic modality and provides a fairly accurate judgment of the pulmonary artery pressure; however, some patients may require an invasive evaluation by right heart catheterization. The definitive management of PH depends on the underlying etiology. Pulmonary arterial hypertension has a specific set of targeted pharmacotherapy, while for other categories of PH, treatment majorly focuses on counseling, management of the underlying disorder, and cardiopulmonary rehabilitation. The 6th World Symposium on PH has catered to all these issues and has incorporated manifold pertinent modifications in all these areas. Hence, we conducted an online survey to gauge the awareness about the entity and its facets among pulmonologists and penned down this review based the current concepts about PH to bridge the gaps in the existing knowledge.



How to cite this article:
Utpat K, Desai U, Doshi K, Joshi JM. Pulmonary hypertension: A simplified pulmonologists' perspective.Med J DY Patil Vidyapeeth 2021;14:255-264


How to cite this URL:
Utpat K, Desai U, Doshi K, Joshi JM. Pulmonary hypertension: A simplified pulmonologists' perspective. Med J DY Patil Vidyapeeth [serial online] 2021 [cited 2021 May 10 ];14:255-264
Available from: https://www.mjdrdypv.org/text.asp?2021/14/3/255/309339


Full Text



 Introduction



Pulmonary hypertension (PH) is a pathophysiologic state characterized by elevation of mean pulmonary artery pressure (mPAP) above a defined value as measured objectively by right heart catheterization (RHC).[1] Since the 1st World Symposium on PH (WSPH) in 1973, this defined value for the definition of PH has undergone pertinent amendments. The current definition is based on a concept that mPAP in a normal subject is 14.0 ± 3.3 mmHg.[2] Hence, to consider mPAP to be pathologically elevated, it has to be >2 standard deviations above this mean value (above the 97.5th percentile). This, hence, suggests a value of mPAP >20 mmHg. However, the elevation of mPAP up to this level can occasionally be seen physiologically in conditions associated with an increase in cardiac output or pulmonary arterial wedge pressure. Therefore, the 6th WSPH Task Force has also suggested to include pulmonary vascular resistance ≥3 Wood Units in the definition of all forms of precapillary PH associated with mPAP >20 mmHg.[2] PH is a morbid condition with its effects on multiple organ systems and casting a pessimistic impact on patient survival and quality of life. The exact prevalence of PH remains obscure; however, it has been postulated to increase with age to the extent of 10%–20% in the general population.[3] Patients with PH can have distressing symptoms; however, the presenting symptoms may be ambiguous and may easily be attributed to the underlying disease or to comorbidities leading to a delay in diagnosis. Furthermore, there is a lack of awareness about this entity among clinicians with respect to its profile, diagnostic options, treatment gamut, and the choice of diagnostics and therapy. This often leads to irrevocable sequelae such as cor pulmonale and right heart failure. Hence, an opportune index of suspicion and timely diagnosis and management is the key to prevent morbidity and mortality. This requires a lucid awareness and a uniform and unambiguous approach among physicians. Pulmonologists predominantly deal with cases of PH occurring to chronic lung diseases (CLDs), but this may not hold true universally. The cases referred to a pulmonologist may also include PH due to other etiologies and secondarily affecting the lung parenchyma in the form of connective tissue diseases or thromboembolic phenomena. Hence, we narrate this Google survey-based review, which adds bricks of knowledge to the deficiencies about the current concepts about various facets of PH among pulmonologists.

 Methodology



We conducted a Google questionnaire-based survey over 55 pulmonologists in India. The questionnaire was based on various facets pertaining to PH. We analyzed the responses and tried to find out the gaps in the existing knowledge and awareness. We searched Cochrane, PubMed, and Google Scholar Database (2000 to recent) search of using a variety of search terms, including “pulmonary hypertension,” “pulmonary arterial hypertension,” and “chronic thromboembolic pulmonary hypertension.” We included meta-analyses, randomized controlled trials, systematic review articles, and consensus or clinical practice guideline documents. We scrutinized the reference lists of relevant articles and guidelines for more references. We then tried to nutshell the data gathered in a simplified fashion with a physician-centric approach and a special consideration given to the areas where we perceived a lack of awareness and clarity.

 Pathophysiology



PH emanates by various mechanisms which ultimately affect the pulmonary arterial or venous bed by heterogeneous mechanisms.[4] Pulmonary arterial hypertension (PAH) results from progressive constriction of the distal pulmonary arteries by infectious or inflammatory insult culminating in a cascade of vasoconstriction, luminal smooth muscle hypertrophy, and subsequently irreversible fibrosis. PH due to left heart disease results from similar changes happening in the pulmonary venous bed.[5] Chronic hypoxia is the fundamental element responsible for the development of PH in patients secondary to chronic respiratory disorders. Vasodestruction of the alveolar-capillary bed due to hypoxic vasoconstriction is the underlying mechanism. CTEPH results as sequelae to thrombotic macrovascular obstruction remodeling of the pulmonary arterial bed.[6] Irrespective of the underlying cause, the result of this persistently raised PAP is an increased pressure overload on the right ventricle, leading to right ventricular dilatation and subsequent right heart failure.[7]

 Classification and Common Causes:



PH is classified into five major groups of causes: [Table 1] PAH (Group 1), PH due to left heart disease (Group 2), PH due to lung disease and/or hypoxia (Group 3), CTEPH (Group 4), and PH with unclear/multifactorial mechanisms (Group 5).[2],[8] As per the Indian registry data for PH, out of the 57 patients, 72% had PAH, 5% had left heart disease, only 7% had CLDs or hypoxemia, and the remaining 16% had CTEPH.[9] However, it was a single-center and a cardiology centric study.{Table 1}

Group 1

The terms PH and PAH are often used interchangeably by clinicians; however, it is crucial to understand that PAH is a subset of PH. It is common in peculiar subpopulations such as those with systemic sclerosis. This group primarily incorporates PAH associated with heritable conditions, human immunodeficiency virus infection, congenital heart diseases, connective tissue diseases, and PAH emanating as a consequence of drug and toxin exposure. The updated clinical classification, as per the WSPH, adds two new subgroups, namely, “PAH demonstrating long-term response to calcium channel blockers (CCBs),” and “PAH with overt features of venous/capillaries involvement,” to Group 1 owing to the distinct therapeutic and prognostic implications.

Group 2

PH induced by left heart disease is an extremely widely prevalent form of PH encountered by a general physician. The congestion of the pulmonary capillary bed leads to an increased backpressure termed as passive PH. It is commonly seen in congestive cardiac failures of various etiologies and in valvular heart diseases.[10]

Group 3

The relatively more common subtype of PH encountered by pulmonologists is the one secondary to underlying CLD. The predominant categories include obstructive airway diseases, interstitial lung diseases (ILD), obstructive sleep apnea (OSA), obesity hypoventilation syndrome, and developmental lung diseases. Among the obstructive lung diseases, the most important cause for PH has been believed to be chronic obstructive pulmonary disease (COPD) and obliterative bronchiolitis (OB). In a study done by Joshi and Gothi, it was uncovered that the incidence of OB could be much more than reported as these cases are frequently misdiagnosed as other airway diseases such as asthma COPD or bronchiectasis. This occurs due to the significant symptom overlap and lack of awareness about this entity among clinicians. Therefore, the actual OB cases coming into light could just be the tip of the iceberg.[11] Gothi et al. stated that PH could be encountered in 19% of cases with OB. OB was as commonly encountered as COPD in their study.[12] Another group of respiratory disorders which is the predominant triggers for PH is ILD, particularly idiopathic pulmonary fibrosis (IPF). In patients with IPF, PH has been reported in 60%–80% of cases and correlated positively with disease progression and mortality.[13],[14] Sleep-related breathing disorders, particularly OSA, is a common category of patients referred to or presenting to a pulmonologist and harboring PH. The association of OSA and PH has been reported in various studies. The pathogenesis is based on hypoxia, acute and chronic cardiovascular events, inflammation, and sympathetic activation. The current ACCP evidence-based clinical guidelines recommend evaluation of OSA by a polysomnography in patients with PH and with clinical suspicion of OSA.[15]

Group 4

Erstwhile considered as a group demonstrating PH due to CTEPH, now this group clearly includes and segregates PH due to CTEPH and due to other pulmonary artery obstructions. CTEPH is a potentially fatal disease, which may be encountered by pulmonologists in various scenarios. It can occur as a complication of acute pulmonary embolism or can be chanced on during evaluation of a patient with respiratory disease with unprecedented worsening of symptoms or with clinicoradiological discordance. The mechanisms involved are macro- or microvascular blockage by thrombotic material or vascular remodeling and scarring.[16] To date, CTEPH is still underdiagnosed and undertreated owing to the suboptimal awareness about this entity and hence low index of suspicion. Miscellaneous causes of pulmonary artery obstructions include heterogenous conditions like malignancies, infections and connective tissue diseases. The common causes are : malignant tumors sucha as sarcoma, renal carcinoma, uterine carcinoma, germ cell tumors and benign tumors such as uterine leiomyoma, arteritis without connective tissue disease, congenital pulmonary artery stenoses and parasites such as hydatidosis.[8]

Group 5

Group 5 consists of an assorted group of entities causing PH by diverse mechanisms. These include chronic hemolytic anemia, myeloproliferative disorders, systemic and metabolic disorders, neurofibromatosis, sarcoidosis, fibrosing mediastinitis, and chronic renal failure with or without hemodialysis.

 Clinical Features



The symptoms in PH result from a demand supply imbalance between the cardiac output and the tissue perfusion and oxygenation. The onset of symptoms is usually insidious, and patients may first report dyspnea and fatigue only with exertion. The symptoms gradually worsen over weeks to months eventually with functional limitation in daily activities too. Other symptoms include chest pain, dizziness, and syncope. However, in patients with PH due to underlying lung diseases and hypoxemia, the symptomatology could be ambiguous due to contribution of symptoms due to the underlying lung disease and symptoms emanating from other comorbidities. However, PH should be suspected in an event of unexplained worsening of symptoms or clinicoradiological discordance. In a national prospective study, Rich et al.[17] elucidated the main symptoms of PH as dyspnea (60%), fatigue (73%), chest pain (47%), syncope (36%), and edema feet (37%). The physical examination in PH is generally noncontributory and lacks sensitivity. The common findings include tachycardia, pedal edema, and a loud pulmonary component of the second heart sound on chest auscultation. The signs on physical examination are subtle. A systematic review showed that the most specific and thus greatest predictive finding of PH was a loud P2.[18] The diagnosis of PH is generally done between in the third to sixth decade and exhibits a female predominance.[19] The risk for its development increases in certain populations such as scleroderma and sickle cell anemia.

 Diagnostic Modalities and Approach



A simple algorithm for approaching pulmonary hypertension in resource limited settings is shown in [Figure 1]. The choice of the test should be guided by various factors such as the likely cause for PH, acceptable deviance from accuracy, and its impact over the therapy decision-making and feasibility issues. Additional testing depends on the differential diagnosis considered. A stepwise algorithm is pertinent to maintain uniformity in the approach and also to minimize the risks and costs of unnecessary testing.[20] This should involve a rational choice of investigations proceeding from least invasive to most invasive and also as a baseline for further follow-ups.[21]{Figure 1}

 Chest Radiograph (Chest X-Ray)



The chest X-ray (CXR) findings that are associated with PH include main and hilar pulmonary arterial dilation (hilar–thoracic ratio, >0.44), a transverse diameter of right descending pulmonary artery ≥17 mm on frontal chest radiograph and cardiomegaly (cardiothoracic ratio >0.5). These lack sensitivity, but could serve as valuable guides to raise a suspicion of the entity in the relevant clinical context.

 Electrocardiogram



PH in itself is not associated with any concrete electrocardiogram (ECG) changes. However, the secondary right atrial and ventricular structural and functional changes may lead to changes on ECG and may denote an advanced nature of the disease. ECG findings include right axis deviation, P-pulmonale, right bundle branch block, and R/S ratio > 1 in lead V1. The higher the pulmonary artery pressure (PAP), the more sensitive is the ECG; ECG features have demonstrated to have prognostic implications only in patients with World Health Organization Functional Class III and IV PAH. However, the relevance of ECG as a screening tool conjectural and normal ECG does not rule out the presence of PH.[20]

 Computed Tomography



Computed tomography (CT) scan is a vital noninvasive modality that can aid in the diagnosis and the categorization of PH by virtue of various features demonstrated. The utilization of a contrast and the resolution will depend on the underlying etiology suspected. The diagnosis of PH commences with an identification of an enlarged pulmonary artery diameter >29 mm, which is usually larger than that of the ascending aorta at the same level with ancillary findings such as increased segmental artery-to-bronchus ratio >1:1 in three or more lobes.[22] CT pulmonary angiography (CTPA) may be used in the setting of suspected CTEPH. Differential energy-based creation of a snapshot of the regional blood volume and detection of perfusion defects based on the same is the fundamental principle perfusion defects.[23] The specific findings can be grouped into pulmonary artery, pulmonary parenchymal, cardiac, and mediastinal findings. Pulmonary artery findings include peripheral calcification, luminal eccentric filling defects, and intra-arterial soft tissue. Parenchymal findings include ground glass opacities, centrilobular nodules, mosaic attenuation, interstitial septal thickening, bronchiectasis, subpleural peripheral opacities, and solid nodules. Cardiac findings include congenital lesions, left ventricular disease, and valvular anomalies. Mediastinal findings include mass lesions, fibrosis, and hypertrophic bronchial arteries. This can guide the clinician on the further line of investigation.[24] However, the findings are not specific with regard to the exact cause for PH.

 Ventilation/Perfusion Scintigraphy



Ventilation/perfusion (V/Q) scintigraphy is a frequently used noninvasive test to screen patients with suspected CTEPH. It provides a fair estimate of the parenchymal perfusion, but needs to be endorsed by a CTPA when it comes to therapeutic or surgical decision-making. However, it has a good negative predictive value.[25]

 Transthoracic Two-Dimensional Doppler Echocardiography and Right Heart Catheterization



The most important diagnostic modalities for PH remain two-dimensional ECHO (2D ECHO) and RHC. The former is noninvasive, whereas the latter is an invasive procedure. Guidelines recommend RHC as the gold standard.[20] However, its availability and feasibility is questionable, particularly in resource-limited settings. The PAP can be gauged noninvasively by 2D ECHO. The underlying principle is based on modified Bernoulli's equation.[26] The estimated pulmonary artery systolic pressure (PASP) by transthoracic 2D ECHO exhibits good correlation with invasively measured mean PAP by RHC as per various studies.[27] The error of calculation is fairly acceptable and is to the tune of only 5–9 mmHg.[28] Overestimation of PAP may occur; however, cases are unlikely to be missed and 2D ECHO has a good negative predictive value. A meta-analysis calculated the accuracy of ECHO versus RHC for diagnosing PH and found a sensitivity of 83%, a specificity of 72%, and an odds ratio of 13.[29] Determination of the right ventricular ejection fraction is pertinent for gauging the right heart functional status. It is challenging because of the complex architecture and properties of the right ventricle. Tricuspid annular plane systolic excursion (TAPSE) and fractional area change (FAC) are commonly used ECHO maneuvers that enable quantitative estimates of RV function. TAPSE is a one-dimensional measure of right ventricular systolic function (RVSF) with its principle based on the hypothesis that displacement of basal and adjacent segments of the RV happens in concordance with the entire RV function. By contrast, FAC is a 2D parameter which enables a better estimation of RVSF as per a meta-analyses.[30] RHC has been considered a gold standard investigation for accurate estimation of PAPs. However, it is an invasive modality and may not be readily available in resource-limited settings. Hence, it should be rationally used in patients when significant PH is suspected and when the patient's management will likely be influenced by RHC results. This includes referral for transplantation, inclusion in clinical trials or registries, treatment of unmasked left heart dysfunction, or in categories of PH like PAH where evidence-based targeted therapy is available.

 Ancillary Tests



Furthermore, certain tests can be done in PH to gauge the functional capacity of the individual. A 6-min walk test (6MWT) is one such test. The 6MWT is a bedside simple, reproducible, and easy-to-perform test. It provides comprehensive and integrated assessment of cardiorespiratory and functional capacity and can also serve as a good tool for follow-up and objective evidence of functional exercise capacity. In a study carried out by Miyamoto et al. in patients with PAH, the 6-min walk distance (6MWD) was reduced in patients with PH as compared to healthy controls. Further, the same authors found that 6MWD <332 m was associated with poor outcome and it predicted the mortality.[31] Sims et al. from their study of COPD patients discovered a negative correlation between PASP values and 6MWD; they found reduction in distance walked of 6 meters for every 3 mmHg rise in PAP.[32] A pulmonary function testing (PFT) including a diffusion capacity for carbon monoxide should be done in patients with CLD to assess the functional status.

 Management



The management of PH should be comprehensive one covering disease-specific targeted therapy wherever available, nonpharmacological therapy including rehabilitation, and preventive therapy including vaccination.[21] Targeted treatment is available only for particular categories of PH such as PAH and CTEPH. For the other categories of PH, there is no robust evidence available about the treatment efficacy. On the other hand, certain therapies have been proven to be harmful. Hence, it is extremely important to follow an evidence-based, patient-centric, and a wise approach in selecting a particular pharmacotherapy in PH.[33]

 Pulmonary Arterial Hypertension



It needs to be understood that not all patients with PAH need pharmacotherapy.[34] Those patients who are relatively asymptomatic with a preserved functional status as gauged by 6MWT can be monitored without drugs. The therapeutic options[35] include CCBs, endothelin receptor antagonist (bosentan), phosphodiesterase Type 5 inhibitors (sildenafil), soluble guanylate cyclase stimulator (riociguat), parenteral or inhaled prostanoids, such as epoprostenol and newer oral prostacyclin agents, such as selexipag and treprostinil.[34] The recommendations of the ESC/ERS guidelines[8] have been retained in the latest 6th WSPH guidelines.[21] Recommendations include performing an acute vasoreactivity testing to predict response to CCBs only in patients with idiopathic PAH, heritable PAH, and PAH associated with drugs and toxin use. Vasoreactive patients should be offered progressively escalated high doses of CCBs and response to therapy should be confirmed at 3–6-month follow-up. A sustained hemodynamic improvement with preservation of the WHO functional Class I/II is considered an adequate response. These patients should be continued on the same medications. Vasoreactive patients without an adequate treatment response belonging to low or intermediate risk should be treated with initial oral combination therapy with an Expansion is Endothelin receptor Antagonist (ERA) and a PDE5i. Nonvasoreactive and treatment-naive patients at high risk should be offered an initial combination therapy, including intravenous PCAs is recommended. Escalation to a double or triple combination therapy should be considered when the initial treatment strategy does not result in hemodynamic response or when these is deterioration in the functional status. Referral for lung transplantation may be considered in the event of failure of maximal medical therapy or a high-risk status. Balloon atrial septostomy can be considered as a palliative or bridging option in patients with suboptimal response to maximal medical therapy and a contraindication or nonfeasibility for a lung transplantation.

 Pulmonary Hypertension Due to Left Heart Disease



The management of this class of PH is mainly supportive, optimization of treatment of comorbidities, and the treatment of the underlying heart disease. This involves optimization of antihypertensive management, management of volume overload with diuretics, addressing the organic cardiac disease, and controlling comorbidities.[5] Vasodilators have no role in the treatment of PH of this category and are not recommended.[33]

 Pulmonary Hypertension Due to Lung Disease



The diagnosis of PH in patients with CLD is essentially based on a 2 D ECHO. However, patients exhibiting a clinicoradiological and an echocardiographic discordance and presenting with a PH out of proportion to the underlying disease severity should be referred for definitive diagnosis to a PH expert center and can be considered for a RHC.[36] The majority of CLD patients, however, show a more severe obstructive and/or restrictive lung disease (IPF with forced vital capacity <70% of predicted, COPD with forced expiratory volume in 1 s <60% of predicted) and accompanying less severe PH (mPAP 20–24 mmHg withPVR ≥3 WU, or mPAP 25–4 mmHg). Current evidence does not endorse therapy with PAH-approved drugs in these patients. Patients with progressed CLD should receive an individualized and holistic care focusing on management of the underlying disease. They may involve airway disease optimization,[36] oxygen therapy, antibiotics, and vaccinations to reduce the infective exacerbations and management of OSA with continuous positive airway pressure therapy. PH in ILD needs a special consideration owing to its multifactorial impacts such as increased sensation of dyspnea, reduced exercise capacity, greater oxygen requirements, and reduced survival.[37] Supplemental oxygen in this group has significant benefit in hypoxic patients in terms of improving quality of life, beneficial effect on pulmonary hemodynamic status, delaying onset of cor pulmonale, and reducing the mortality.

 Chronic Thromboembolic Pulmonary Hypertension



Pulmonary Endarterectomy is the first line therapy in patients with CTEPH and is the only therapy that can be curative. It requires an operability assessment by a multidisciplinary team at a center of excellence. It has proven benefits in terms of improvement of hemodynamics, symptoms, and life expectancy. Patients whose disease is anatomically not amenable to surgery or who have medical contraindications for surgery may benefit from medical therapy or from balloon pulmonary angioplasty (BPA). Riociguat is the only medication approved by the guidelines for the treatment of inoperable or residual CTEPH. The recommendations are based on the basis of results of a single 16-week randomized controlled trial that showed improvements in New York Heart Association (NYHA) functional class, 6MWD, health-related quality of life, and pulmonary hemodynamics.[38] Lifelong anticoagulation is recommended in these patients irrespective of surgical or medical management employed.[39] Another promising option in patients who are poor surgical candidates is BPA. A Japanese study including 170 patients who underwent BPA over a 7-year period documented sustained hemodynamic improvements in mPAP and pulmonary vascular resistance with improved 1-, 3-, and 5-year survival rates and with a low incidence and low severity of complications.[40]

 Multifactorial Pulmonary Hypertension



The data pertaining to treatment of PH in this subgroup are deficient. Treatment focuses on the management of underlying disease, rehabilitation, and supportive care. In patients with sickle cell disease pharmacotherapy with hydroxyurea and long-term transfusion therapy are options available of some benefit on the pulmonary hemodynamics. However, vasodilators and other PH-lowering agents are not recommended.

 Supportive Management



The supportive care of patients with PH is a prime modality of management, especially in patients belonging to categories where evidence does not recommend a targeted pharmacotherapy. The data supporting the role of this palliative and ancillary care are variable. The components of supportive care include patient counseling, immunization, oxygen therapy, smoking cessation, diuretic therapy in selected subgroup, contraception, anticoagulation, and exercise training. Vaccination with seasonal influenza vaccine and age-recommended pneumococcal polysaccharide or conjugate vaccine with a suitable schedule is also beneficial.[41] Patients should be encouraged to adopt an active lifestyle with maximum possible ambulation to avoid deconditioning. This may involve simple domiciliary exercises or a formal exercise training a rehabilitation center.[42] Pulmonary rehabilitation which is a multidisciplinary program of care in patients with CLDs can be extended to PH due to other etiologies with a beneficial effect as shown in a study by Talwar et al.[43] Women living with PH, particularly PAH, need to be advised about appropriate contraception taking into consideration the risks and hemodynamic burden imposed by a pregnancy and its complications.[44] Furthermore, PH tends to cause a significant psychological impact on the individual with feelings of anxiety and depression.[45] These need to be optimally addressed and a psychological support and counseling may be necessary.

 Recent Advances and Way Forward



Innovative diagnostic modalities include V/Q single photon emission CT; dual-energy CT; dynamic contrast-enhanced magnetic resonance; and potential biomarkers such as pentraxin-3 (serum), angiogenin, tumor necrosis factor-α (in breath condensate), interleukin-6, transforming growth factor-β, brain natriuretic peptide, and vascular endothelial growth factor. The medical therapy basket has little to offer in PH other than PAH. Newer drugs in PAH include bone morphogenetic protein signaling and prostacyclin analog pathway modifiers in the form of tacrolimus and ralinepag which are in clinical trial phase 2 currently.[46] An additional fertile area of research which is currently in the budding phase includes the role of stem cells in the management of PAH. Lung or heart lung transplant offers a ray of hope as a destination therapy in a select subgroup. The desirable candidates include a relatively younger age group with minimal comorbidities and persistent or progressive NYHA functional class III or IV disease despite optimal medical therapy.

 Conclusion and Highlights of Our Survey



Our review is noteworthy from various aspects. It is composed at the juncture of the 6th WSPH bringing into light salient amendments in the definition, diagnostic algorithm, and the treatment recommendations. It incorporates all these pearls in a simplified language. It is the first Indian review of its kind involving a Google questionnaire-based approach which seeks to fulfill the unmet needs and the gaps in knowledge at the physician and pulmonologist level. The contemplation about the gaps in knowledge was related to multiple areas such as definitions, classification, diagnostics, and management [Appendix 1]. The overall analysis of the responses revealed that there is ambiguity and a gap in knowledge about the available diagnostic modalities, rational utilization of resources, and prioritization of various tests depending on the clinical severity. Comparatively the awareness about the treatment modalities and selection of appropriate treatment in the pertinent clinical situation is fair. We, hence, emphasize a need for increases awareness among physicians about the various diagnostic modalities and uniformity in the diagnostic algorithm. We recommend guideline-based and a patient-centric multimodality team approach in the management of this complex condition.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Appendix 1: Google survey, summary of responses

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