The Early Detection of Pulmonary Hypertension

Abstract

Background

Up to 1% of the world population and 10% of all persons over age 65 suffer from pulmonary hypertension (PH). The latency from the first symptom to the diagnosis is more than one year on average, and more than three years in 20% of patients. 40% seek help from more than four different physicians until their condition is finally diagnosed.

Methods

This review is based on publications retrieved by a selective literature search on pulmonary hypertension.

Results

The most common causes of pulmonary hypertension are left heart diseases and lung diseases. Its cardinal symptom is exertional dyspnea that worsens as the disease progresses. Additional symptoms of right heart failure are seen in advanced stages. Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are rare, difficult to diagnose, and of particular clinical relevance because specific treatments are available. For this reason, strategies for the early detection of PAH and CTEPH have been developed. The clinical suspicion of PH arises in a patient who has nonspecific symptoms, electrocardiographic changes, and an abnormal (NT-pro-)BNP concentration. Once the suspicion of PH has been confirmed by echocardiography and, if necessary, differential-diagnostic evaluation with a cardiopulmonary stress test, and after the exclusion of a primary left heart disease or lung disease, the patient should be referred to a PH center for further diagnostic assessment, classification, and treatment.

Conclusion

If both the (NT-pro-)BNP and the ECG are normal, PH is unlikely. Knowledge of the characteristic clinical manifestations and test results of PH is needed so that patients can be properly selected for referral to specialists and experts in PH.

cme plus

This article has been certified by the North Rhine Academy for Continuing Medical Education. The questions on this article can be found at http://daebl.de/RY95. The submission deadline is 30 November 2024.

Participation is possible at cme.aerztebatt.de

Pulmonary hypertension (PH) is a potentially life-threatening cardiopulmonary condition defined by a mean pulmonary artery pressure (mPAP) > 20 mm Hg, as measured with a right heart catheter. In PH, chronic vascular remodeling results in an increase in pulmonary vascular resistance (PVR) in the pulmonary circulation. Consecutive to this, pulmonary arterial pressure (PAP) and right heart afterload also increase, ultimately leading to right heart failure. PH is subdivided into five groups based on the underlying pathophysiology (Table 1) (1). In total, up to 1% of the world population and 10% of over 65-year-olds suffer from PH (2). The most common causes of PH include left heart diseases and lung diseases (2, 3). Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are rare and more difficult to diagnose. They are of particular importance since, unlike in the case of PH due to left heart disease or lung disease, specific treatment options are available. Due to nonspecific symptoms, the diagnosis of PAH and CTEPH is usually delayed (1). The latency in PAH and CTEPH from first symptom to diagnosis is more than 1 year on average (4, 5). However, in the United Kingdom for example, 20% of PH patients wait more than 3 years for a diagnosis, and 40% of patients seek help from more than four different physicians before their condition is diagnosed (4). In the USA, it can even take a median of over 2 years and require six different physicians to diagnose PAH (6). Delayed initiation of therapy is associated with increased right heart load, which is the determining factor in the prognosis of PH (7, 8). To ensure early diagnosis and prompt initiation of treatment, knowledge of typical symptoms and test results is essential in order to refer selected patients to specialists and experts (Table 2).

Table 1. Classification of pulmonary hypertension (modified from [1]).

Group	Name/description*	Primarylocalization	Most importanttriggering disorders	Frequency
1	Pulmonary arterial hypertension (PAH)	Pre-capillary	Idiopathic; heritable; associated with drugs/toxins, connective tissue disorders, HIV infection, portal hypertension, congenital heart defects, schistosomiasis	Rare (incidence: 6/million, prevalence: 48–55/million) (9)
2	Pulmonary hypertension associated with left heart disease	Post-capillary	Heart failure, valvular heart disease	Very common (50–80% of cases, > 50 % in left-sided heart failure) (2, 3)
3	Pulmonary hypertension associated with lung disease/ hypoxia	Pre-capillary	Chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD)	Common (40% of cases, prevalence in COPD: 39%, prevalence in ILD: approximately 10%) (2, 10, 11)
4	Pulmonary hypertension associated with pulmonary artery stenosis	Pre-capillary	Chronic thromboembolic pulmonary hypertension (CTEPH)	Rare (incidence: 3–6/million, prevalence: 26–38/million) (9)
5	Pulmonary hypertension due to unexplained or multifactorial mechanisms	Pre-/post-capillary	Hematological, systemic, metabolic conditions	Rare/unknown (1, 12)

*Pre-capillary pulmonary hypertension: mean pulmonary artery pressure (mPAP) > 20 mm Hg; pulmonary vascular resistance (PVR) > 2 WU and pulmonary arterial wedge pressure (PAWP) ≤ 15 mm Hg, due to isolated damage in the pulmonary vascular system; post-capillary pulmonary hypertension: mPAP > 20 mm Hg; PVR ≤ 2 WU and PAWP > 15 mm Hg, due to a marked congestive component caused by backward failure of the left ventricle

Table 2. Differential diagnostic criteria to distinguish between the PH subgroups (modified from [1, e15]).

Diagnostic assessment	Pulmonary arterial hypertension (group 1)	Pulmonary hypertension associated with left heart disease (group 2)	Pulmonary hypertension associated with lung disease/ hypoxia (group 3)	Chronic thromboembolic pulmonary hypertension (group 4)
Patient history and symptoms	PAH risk factors possibly present, presentation as unexplained exertional dyspnea is typical, symptoms depending on precise subgroup	Patients tend to be older, possibly known left heart disease and/or clinical signs of left heart disease, symptoms depending on the underlying disease	Patients tend to be older, male,and ex-smokers, O2 requirement is frequent, possibly known lung disease and/or clinical signs of lung disease, symptoms depending on the underlying disease	CTEPH risk factors possibly present (particularly after phlebothrombosis or pulmonary embolism), presentation as unexplained exertional dyspnea is typical
Pulmonary function tests and blood gas analysis*	Normal spirometry, DLCO → / ↘ , PaO2 →/↓, PaCO2 ↓	Normal spirometry DLCO → / ↘ , PaO2 →/↓, PaCO2 →	Abnormal spirometry (obstructive/restrictive) DLCO ↘ / ↓, PaO2 ↓, PaCO2 →/↓/↑	Normal spirometry DLCO → / ↘ , PaO2 →/↓, PaCO2 →/↓
Cardiopulmonary exercise tests	VE/CO2 ↑, PETCO2 ↓ (on exertion ↓), EOV absent	VE/VCO2 ↗, PETCO2 → (on exertion ↑), EOV	VE/VCO2 ↗, PETCO2 → (on exertion ↑)	VE/VCO2 ↑, PETCO2 ↓ (on exertion ↓), EOV absent
Chest radiography	Right heart enlargement,pulmonary artery dilatation, pruning of peripheral pulmonary vessels	Left heart enlargement (possibly combined heart enlargement), signs of pulmonary venous congestion, pulmonary artery dilatation	Signs of lung disease, right heart enlargement, pulmonary artery dilatation, pruning of peripheral pulmonary vessels	Right heart enlargement,pulmonary artery dilatation, pruning of peripheral pulmonary vessels
Chest computed tomography	Right heart enlargement,pulmonary artery diameter > 30 mm, pulmonary-artery-to-aorta ratio > 0.9	Left heart enlargement (possibly combined heart enlargement), signs of pulmonary venous congestion, pulmonary artery diameter > 30 mm	Signs of lung disease, right heart enlargement, pulmonary artery diameter > 30 mm, pulmonary- artery-to-aorta ratio > 0.9	Right heart enlargement, pulmonary artery diameter > 30 mm, pulmonary-artery-to-aorta ratio > 0.9, signs of CTEPH on CTPA
Cardiac magnetic resonance imaging	Right heart enlargement and hypertrophy, possible reduction in RVEF	Left heart enlargement and hypertrophy (possibly combined), possible reduction in LVEF (possibly also RVEF)	Right heart enlargement and hypertrophy, possible reduction in RVEF	Right heart enlargemen tand hypertrophy, possible reduction in RVEF

* Reference values: DLCO: 80% of target, paO₂ > 60–80 mm Hg, paCO₂: 35–45 mm Hg

CTEPH, chronic thromboembolic pulmonary hypertension; CTPA, computed tomographic pulmonary angiogram;

DLCO, diffusing capacity of the lungs for carbon monoxide; EOV, exercise oscillatory ventilation; LVEF, left ventricular ejection fraction;

paCO₂, arterial partial pressure of carbon dioxide; paO₂, arterial partial pressure of oxygen; PAH, pulmonary arterial hypertension; P_ETCO₂, end-tidal CO₂ pressure;

PH, pulmonary hypertension; RVEF, right ventricular ejection fraction; VE/VCO 2 slope, ventilatory equivalent for CO 2

Methods

This review is based on publications retrieved by a selective literature search on the clinical picture of PH based on the current ESC/ERS guideline (1). The following search terms were used in a wide variety of combinations to select literature in Medline: “pulmonary hypertension,” “prevalence,” “incidence,” “symptoms,” “diagnosis,” “early detection,” “screening,” “electrocardiogram,” “bnp,” “nt-pro-bnp,” “echocardiography,” “chest x-ray,” “computed tomography,” “magnetic resonance imaging,” “pulmonary function test,” and “cardiopulmonary exercise test.” Only German- and English-language articles were taken into consideration.

Diagnostic algorithm

If PH is suspected on the basis of a combination of nonspecific symptoms, electrocardiographic changes, and measurement of (NT-pro-)BNP, echocardiography should be performed to confirm the suspicion of PH. In the case of uncertainty, suspicious patterns in cardiopulmonary exercise tests (CPET) can help in this process. Persistent suspicion of PH or suspected hemodynamically severe PH should prompt referral of patients to PH centers for diagnosis, classification, and treatment once group-2 or -3 PH has been excluded (Figure) (1, 13).

Figure.

Diagnostic algorithm for the early detection of pulmonary hypertension (modified from [1, 13])

Comments: PH: pulmonary hypertension, PAH: pulmonary arterial hypertension, CTEPH: chronic thromboembolic pulmonary hypertension, *¹It is essential here to interpret any findings that are potentially present based on a consideration of all the findings, *²pulmonary vascular resistance > 5 WU, *³ intermediate echocardiographic probability: TRV ≤ 2.8 m/s and other signs or TRV = 2.9–3.4 m/s, high echocardiographic probability: TRV = 2.9–3.4 m/s and other signs or TRV > 3.4 m/s

Patient history, symptoms, and signs

Symptoms of PH at disease onset are usually only observed during exercise, but later on even at rest (14). The cardinal symptom of PH is progressive exertional dyspnea (15). Other possible symptoms include reduced exercise capacity, chest discomfort, palpitations, edema, and syncope. More rarely, chest pain on exertion, hoarseness, cough, or hemoptysis occur. Right heart failure can cause distended and pulsatile jugular veins, hepatojugular reflux, hepatosplenomegaly and ascites, peripheral cyanosis, dizziness, pallor, cold extremities, and prolonged capillary refill time. Typical findings on auscultation include a loud second heart sound, the presence of a third and/or fourth heart sound, as well as a systolic murmur (tricuspid regurgitation) and/or a diastolic murmur (pulmonary regurgitation) (13–16). Although the common symptoms of PH (eTable 1) are nonspecific, PAH or CTEPH should always be considered as a differential diagnosis, since there are specific treatments for these two entities.

eTable 1. Frequency of clinical symptoms and signs of pulmonary hypertension at the time of diagnosis (e14, e48, e49).

Symptom/sign	Frequency (%)
Dyspnea	87–98
Loud 2nd heart sound	93
Fatigue	26–73
Chest pain/discomfort	8–48
Systolic murmur (tricuspid regurgitation)	40
4th heart sound	38
Edema	21–38
Syncope	8–36
Palpitations	6–33
Dizziness	11–26
3rd heart sound	23
Cough	22
Cyanosis	20
Diastolic murmur (pulmonary insufficiency)	13
Anxiety	6
Hemoptysis	5

The patient history can prompt suspicion of the etiology possibly underlying PH (Table 2). Typical risk factors such as previous embolism/thrombosis (in particular, fulminant pulmonary embolism), thrombophilia (in particular, antiphospholipid syndrome and elevated factor VIII), certain comorbidities (malignancy, myeloproliferative disorders, chronic osteomyelitis, chronic inflammatory bowel disease, and treated hypothyroidism), previous splenectomy, presence of a ventriculoatrial shunt, and infections of chronic venous accesses or devices (for example, pacemakers) are suggestive of CTEPH (17–19). Risk factors for PAH include certain disorders (connective tissue diseases, especially systemic sclerosis; portal hypertension; HIV infection; certain heart defects; schistosomiasis), certain mutations (for example, BMPR2 mutations), or the abuse of certain drugs or toxins (for example, methamphetamines or appetite suppressants) (1).

Electrocardiogram

Typical electrocardiographic changes in PH (Figure 1, eTable 2) include:

Figure 1.

ECG signs of pulmonary hypertension

Left: QRS axis > 120°, center: P pulmonale (0.4 mV in II), right: inverted T waves V1–V5

eTable 2. Frequency of electrocardiographic signs in pulmonary hypertension.

ECG sign	%	Source
Normal ECG on diagnosis	5–14	(28, e50)
P pulmonale	0–35	(26, e51)
QRS axis > 90°	35–78	(e51, e52)
SI-QIII type	7–65	(e53, e54)
SI-SII-SIII type	7	(e54)
Right ventricular hypertrophy (R V1(,V2) + S V5, V6 > 1.05 mV)	32–74	(e54, e55)
Large R wave in V1 (> 0,6 mV)	15–53	(e54, e56)
Large S wave in n V5 (> 1,0 mV)	9–37	(23, e54)
Large S wave in V6 (> 0,3 mV)	45–75	(23, e54)
Right bundle branch block	5–50	(e51, e57)
qR in V1	6–61	(26, e55)
T wave inversion in II	31	(e54)
T wave inversion in III	49	(e54)
T wave inversion in aVF	41	(e54)
T wave inversion in V1	64–87	(e54, e58)
T wave inversion in V2	51	(e54)
T wave inversion in V3	60	(e54)

• Right axis deviation or SI-QIII/SI-SII-SIII type

• Right ventricular hypertrophy

• Large R waves in V1 and V2 and deep S waves in V5 and V6

• Right bundle branch block

• qR pattern in V1 as well as ST depressions and T-wave inversions, particularly in leads V1–V3, II, III, and aVF (20–24, e62).

Right axis deviation (QRS axis >90°), qR pattern in V1, and low S-wave amplitude in V1 (≤ 0.2 mV) have high positive predictive values (93%, 95%, and 100%, respectively) in adults with suspected PH (25, 26). However, a normal electrocardiogram does not reliably exclude PH, since it can be completely normal in mild PH (21, 27, 28). In autopsy studies, ECG parameters for right ventricular hypertrophy show high specificity (83–100%), but only low sensitivity (18–44%) (29, 30). In addition, the positive and negative predictive values (PPV, NPV) for ECG criteria of right ventricular hypertrophy (0–100%, 18–44%) are insufficient for reliable diagnosis/exclusion (26, 31). Having said that, if the ECG and (NT-pro-)BNP are normal, PH is unlikely (32, 33).

Laboratory diagnostics

(NT-pro-)BNP is a marker of a decompensated cardiovascular state and is released from the myocardium during pressure and/or volume stress (34, 35). It is often elevated in patients with PAH and CTEPH (36–39). However, a high false positive rate should be expected in the case of additional left heart disease since it is by no means PH-specific (39). A meta-analysis showed that (NT-pro-)BNP values were able to detect PAH in patients with systemic sclerosis with a sensitivity and specificity of only 67% and 84%, respectively (40). However, if not only the (NT-pro-)BNP level but also the ECG is normal, PH is unlikely (32, 33).

Echocardiography

By considering the peak systolic velocity of tricuspid regurgitation (TRV) as the main parameter alongside other secondary echocardiographic findings (Figure, Figure 2, eTable 3), it is possible to estimate the echocardiographic probability of PH. Meta-analyses have shown that echocardiography is able to detect PH with a sensitivity of 83–87% and a specificity of 72–86% (e1–e3). However, there is evidence that its sensitivity for the detection of PAH may be lower (71–76%), while comprehensive data on its quality in CTEPH are lacking (e1, e4). Furthermore, significant inaccuracies (± 10 mm Hg difference to invasive measurement) are observed in the estimation of systolic pulmonary artery pressure (sPAP) in 48% of patients (e5). Moreover, TRV cannot be determined in all patients, since only 90% of patients with PH exhibit tricuspid valve regurgitation (e6). In such cases, secondary echocardiographic findings are of great importance. Additional signs of left heart pathology (left heart enlargement, valvular disorders, reduced left ventricular ejection fraction) should prompt consideration of group-2 PH (e7, e8).

Figure 2.

Echocardiographic signs of pulmonary hypertension

Top: severe triscupid valve regurgitation in continuous-wave (CW) Doppler TRV > 3.4 m/s, bottom: paradoxical septal motion with ‘D’ sign in the parasternal short axis

eTable 3. Echocardiographic signs of pulmonary hypertension (1, e59–e61).

Parameter	Cut-off value	Significance	Supplementary information
IVC diameter	> 21 mm	IVC congestion
IVC respiratory collapse	< 50% in brief, deep inspiration or < 20 % in normal respiration	IVC congestion
Right atrial pressure (RAP)	15 mm Hg	Congestion in the right atrium	Estimate using diameter and respiratory collapse of IVC 3 mm Hg: IVC not dilated and respiratory collapse 8 mm Hg: inconsistent results 15 mm Hg: IVC dilated and respiratory collapse absent
Right atrial area	> 18 cm2	Right atrial dilatation
Peak systolic tricuspid regurgitation velocity (TRV)	> 2.8 m/s	Tricuspid valve regurgitation due to congestion
Right ventricular width and length	Width: 41 mm at base or 35 mm at mid-level Length: 83 mm	Widened: right ventricular dilatation Elongated: right ventricular enlargement
Basal ratio of right and left ventricle (RV:LV)	> 1	Right ventricular enlargement or dilatation	Right ventricle may be apex-forming
Left ventricular eccentricity index (LVEI)	> 1.1	Left ventricular diameter < right ventricular diameter
Morphology of the interventricular septum	Flattening, septum bows in a D shape into the left ventricle (D sign)	Right ventricular pressure > left ventricular pressure
Tricuspid annular plane systolic excursion (TAPSE)	< 18 mm	Right ventricular systolic dysfunction	Measurement of the distance of the longitudinal systolic excursion of the lateral tricuspid annulus in M-mode
TAPSE/sPAP	< 0.55 mm/mm hg	Synchronization of the right ventricle and the pulmonary arteries (RV–PA coupling)
Right ventricular fractional area change (RV-FAC)	< 35%	Right ventricular systolic dysfunction	(End-diastolic area–end-systolic area)/end-diastolic area*100
Peak systolic velocity of the tricuspid annulus (tricuspid annulus velocity, S′ wave)	< 9.5 cm/s (pulsed doppler)	Right ventricular systolic dysfunction
Right ventricular outflow tract (RVOT) acceleration time of pulmonary ejection	< 105 ms	Pulmonary congestion
Mid-systolic notch in pulmonary ejection	Present	Pulmonary congestion
Systolic pulmonary artery pressure (sPAP)	> 35 mm Hg	Pressure increase in the pulmonary arteries	Measurable following exclusion of pulmonary stenosis in tricuspid valve regurgitation sPAP = TRPG + RAP
PA diameter	> 25 mm	Congestion in the pulmonary arteries
Pericardial effusion	Present	Right heart congestion

LV, left ventricle; PA, pulmonary artery; RVOT, right ventricular outflow tract; RV, right ventricle; TRV, peak systolic tricuspid regurgitation velocity;

TRPG, tricuspid regurgitation pressure gradient; VC, inferior vena cava

Cardiopulmonary exercise tests

Particularly in patients without risk factors for PAH or CTEPH, CPET (for example, spiroergometry) can indicate a pulmonary vascular component to the underlying symptoms, even if echocardiography points to an intermediate probability, and can be helpful in establishing the diagnosis (Table 2) (1, 16). There is evidence that CPET is better able to detect PAH and CTEPH in early stages than is echocardiography (e4, e9–e12). Furthermore, in the case of exertional dyspnea of unclear etiology, it is possible to differentiate between PH and other heart and lung diseases and, in the presence of PH, between PAH and CTEPH (1, 16, e13). The assessment of a CPET requires specialized knowledge and should be performed by experienced personnel (e14). However, CPET are not able to reliably confirm PH (16).

Exclusion of group-2 or group-3 pulmonary hypertension

For patients with non-severe PH in groups 2, 3, or 5, there is no evidence that they benefit from PAH-specific medication. Thus, for these patients, the focus of treatment is on the underlying disease and a referral to a PH center does not appear necessary (1).

Pulmonary function tests and blood gas analysis

Typically, pathological pulmonary function patterns are found in PH due to lung diseases (obstructive/restrictive lung disorder, for example in COPD/interstitial lung disease). Pulmonary function tests may be completely normal in PAH or CTEPH (Table 2) (1).

Chest radiography

Imaging with chest X-ray shows signs such as enlargement of the right heart silhouette, dilatation of the pulmonary arteries, and pruning of peripheral pulmonary vessels, pointing to the presence of PH (14, 16, e16). However, normal findings do not rule out PH (1). Moreover, left heart disease or lung disease may be discovered as a possible cause of PH (Table 2) (14, e16).

Computed tomography of the chest

Chest computed tomography (CT) can yield important indications of PH: for example, an enlarged pulmonary artery diameter > 30 mm (sensitivity: 58–75%, specificity: 81–90%, positive predictive value [PPV]: 96–98%, negative predictive value [NPV]: 24–32%), a pulmonary-artery-to-aorta ratio > 0.9 (sensitivity: 65–86%, specificity: 55–89%), or right heart enlargement (e16–e21).

In addition, computed tomography pulmonary angiogram (CTPA) can reveal signs of CTEPH (e22–e24). If CTEPH is clinically suspected and evaluated by experts—in contrast to cases where there is no clinical suspicion and sensitization for radiological signs of CTEPH is lacking—the diagnostic accuracy of CTPA is high (98% sensitivity, 99% specificity, PPV: 94%, NPV: 100% versus 28% sensitivity) (e25). Furthermore, computed tomography is able to yield indications of left heart disease and lung diseases (Table 2) (e16).

Cardiac magnetic resonance imaging

Although cardiac magnetic resonance imaging (MRI) is the gold standard for the determination of right ventricular volume and function, it plays a secondary role in the diagnosis of pulmonary hypertension since it is unable to reliably exclude this disorder (e15, e16, e26). However, if PH is present, one may notice a reduced right ventricular ejection fraction and hypertrophy or dilatation of the right heart (e15). MRI may also point to other chronic heart diseases (Table 2) (1).

Referral to a PH center

Persistent suspicion of PH or suspected hemodynamically severe PH should prompt referral of patients to PH centers for diagnosis, classification, and treatment once group-2 or -3 PH has been excluded, since these centers appear to be superior to other centers in terms of diagnosis and treatment (1, 13, e27, e28). If characteristic mismatches are found on ventilation-perfusion scintigraphy, CTEPH should be hemodynamically confirmed by means of right heart catheterization. By measuring and calculating mPAP, PVR, and pulmonary arterial wedge pressure (PAWP), it is possible to verify the diagnosis, classify PH (pre-/post-capillary), and determine hemodynamic severity. Finally, CTPA and digital subtraction angiography or pulmonary artery angiography are used to assess the operability of CTEPH. If CTEPH is ruled out based on the absence of mismatches on ventilation-perfusion scintigraphy (gold standard, sensitivity: 90–100%, specificity: 90–100%), one should consider PAH in the presence of risk factors. If right heart catheterization reveals PH, additional tests are able to diagnose the definitive cause of PAH or PH of multifactorial or unclear etiology (1, 14, 16, e29).

Screening and early detection

The diagnosis of PAH and CTEPH takes on average more than 1 year, and most patients present at advanced stages of disease. Retrospective investigations of the French PAH registry, the IntinérAIR-Sclérodermie program, and the European CTEPH registry suggest that early treatment of PAH and CTEPH could prolong survival (4, 5, e27, e30–e32). Screening the general population is not recommended and would lead to an immense use of resources in the healthcare system as well as overdiagnosis due to unduly high rates of false-positive results, particularly for the rare subtypes of PAH and CTEPH (1).

Screening in PAH

Asymptomatic high-risk groups (systemic sclerosis [prevalence: 8–19%] [e4, e33]), BMPR2 mutations (penetrance: 14–42%, prevalence: 70%, annual incidence: 2.3% [e34, e35]), portal hypertension prior to liver transplantation (prevalence: 2–9% [e36, e37]) as well as first-degree relatives of patients with heritable PAH) should be screened (1, 13). For patients with systemic sclerosis, one of the established algorithms (DETECT, ASIG) should be used (e4, e38). Additional CPET may be judicious if the risk of PAH is low, in order to avoid unnecessary right heart catheterization (e9, e10). Annual echocardiographic screening can be recommended for patients with portal hypertension who are listed for liver transplantation, since mortality is higher in severe PH following liver transplantation (71% mortality in the first 36 months) (e26, e37, e39). In the case of hereditary components (heritable PAH and, in particular, BMPR2 mutations), first-degree relatives should be offered genetic counseling and, if they test positive for the genotype, screening with, for example, annual echocardiography (1, 13).

Furthermore, efforts should be made to ensure early detection of symptomatic patients in risk groups (portal hypertension [prevalence: 2–6 %] [13]), HIV infection (prevalence: 0.5% [e40]), other connective tissue diseases, and congenital heart defects (prevalence: 3–7% [e41, e42]) (1, e30). If portal hypertension is present but the patient is not being prepared for liver transplantation, echocardiographic screening is recommended (1, 13). In the case of HIV infection, screening for PAH should be performed if signs of the first symptoms are seen or in the presence of more than one risk factor. There are no clear recommendations on the extent of screening in HIV infection (13). For congenital heart defects, screening should be carried out 3–6 months after the defect has been corrected and then at further appropriate intervals, much like patients with persistent left-to-right shunt, by means of patient history, physical examination, ECG, and echocardiography (13).

Screening in CTEPH

Since the thrombi usually dissolve after pulmonary embolism (PE), general screening for CTEPH following PE is not currently recommended (e43, e44). However, given that this does not occur in all patients and CTEPH occurs in 3.2% of PE survivors, echocardiography and ventilation-perfusion scintigraphy should be performed to search for perfusion defects in the case of persistent or new-onset dyspnea following PE (e43, e45, e46). CPET may also be diagnostically helpful (e11, e12). The optimal time for the early detection of CTEPH is probably in the 3- to 6-month range following PE (e43, e46). One study was able to diagnose CTEPH at 4 months post PE using an algorithm comprising an assessment of CTEPH probability (risk factors and symptoms), ECG criteria, NT-pro-BNP values, and echocardiography, with a sensitivity and specificity of 85% and 100%, respectively (PPV: 100%, NPV: 100%) (e47).

Conclusion

Pulmonary hypertension is a common disease in old age. While rare, PAH and CTEPH are particularly important since specific treatment forms are available. The diagnosis of PH is challenging due to its nonspecific symptoms and is often delayed. Having said that, echocardiography is able to quickly and reliably assess the probability of PH. A complementary cardiopulmonary exercise test may be helpful in certain situations. Moreover, normal ECG and (NT-pro-)BNP findings largely rule out PH. The definitive diagnosis, classification, and treatment require hemodynamic confirmation by means of right heart catherization and are performed in PH centers once PH due to left heart disease or lung disease has been excluded. Certain risk groups benefit from screening for PAH or CTEPH. In the early detection of PH, particular importance is attached to primary medical care, since it is from here that selected patients should be referred to specialists and experts.

Questions on the article in issue 48/2023:

The Early Detection of Pulmonary Hypertension

The submission deadline is 30 November 2024. Only one answer is possible per question.

Please select the answer that is most appropriate.

Question 1

What is the definition of pulmonary hypertension?

1. Mean intrapleural pressure (iPAP) > 10 mm Hg

2. Mean pulmonary artery pressure (mPAP) > 20 mm Hg

3. Mean pulmonary venous pressure (mPVP) > 20 mm Hg

4. Positive end-expiratory pressure (PEEP) > 10 mm Hg

5. An afterload increased by half

Question 2

Approximately what percentage of over 65-year-olds suffer from pulmonary hypertension worldwide?

1. 0.5%

2. 2%

3. 10%

4. 25%

5. 33%

Question 3

Which of the following symptoms is cited in the text as a cardinal symptom of pulmonary hypertension?

1. Progressive dyspnea on exertion

2. Cyanosis

3. Pain in the right arm and shoulder

4. Progressive hyperventilation

5. Hemoptysis

Question 4

Which of the following problems in pulmonary hypertension makes the prompt diagnosis and immediate initiation of treatment so important?

1. Insufficient oxygen supply to the brain

2. Strain on the right heart

3. Damage to the pulmonary alveoli

4. Strain on the left heart

5. Increased bronchial infections

Question 5

Which is the commonest form (at 50–80% of cases) of pulmonary hypertension?

1. Idiopathic pulmonary arterial hypertension

2. Pulmonary hypertension associated with left heart disease

3. Pulmonary hypertension associated with pulmonary artery obstruction

4. Pulmonary hypertension due to unexplained or multifactorial mechanisms

5. Pulmonary hypertension associated with lung diseases/hypoxia

Question 6

Which of the following combinations of auscultation findings are typically found in pulmonary hypertension?

1. Soft second heart sound and loud third heart sound

2. Second heart sound absent and fourth heart sound present

3. Split second heart sound and loud fourth heart sound

4. Loud second heart sound and third heart sound present

5. Split third heart sound and loud fourth heart sound

Question 7

Which of the following electrocardiographic changes are typically seen in pulmonary hypertension?

1. P pulmonale and right bundle branch block

2. Small R waves in V1 and V2 and left bundle branch block

3. P biatriale and left bundle branch block

4. ST segment elevation and large S waves in V5 and V6

5. A qT pattern in V1 and large R waves in V5 and V6

Question 8

Which structure of the heart releases the marker (NT-pro-)BNP?

1. The endothelium

2. The fascia

3. The myocardium

4. The epicardium

5. The coronary arteries

Question 9

What does the abbreviation CTEPH stand for in the text?

1. Computed tomography to evidence pulmonary hypertension

2. Chronic treatment-refractory pulmonary hypertension

3. Cardiac thromboembolic pulmonary hypertrophy

4. Comorbid treatment-refractory pulmonary hypertrophy

5. Chronic thromboembolic pulmonary hypertension

Question 10

Which cut-off value of peak systolic tricuspid regurgitation velocity indicates a high echocardiographic probability of pulmonary hypertension even in the absence of other echocardiographic signs?

1. < 5.1 m/s

2. < 3.4 m/s

3. > 5.1 m/s

4. > 3.4 m/s

5. > 0.9 m/s