Introduction
Pulmonary hypertension (PH) is a disease that can only be appropriately managed in
the ‘rich’ developed countries, as both diagnostic and therapeutic interventions are
extremely expensive and expectations for these to be adopted by the developing, economically-challenged
countries are neither practical nor realistic. Furthermore, most of the enormous advances
in understanding the pathobiology of PH and the subsequent evidence-based diagnostic
and complex treatment algorithms came from the developed world.
1
It has been estimated that PH is likely to be more prevalent in the developing world
(DW) because of the presence of many risk factors affecting millions of people, most
of whom cannot get any sort of treatment.
2
Such risk factors are believed to be more common in the DW compared to the developed
world and include infections (such as schistosoma, HIV, viral hepatitis, etc.), uncorrected
congenital heart diseases, hemolytic anemias, smoking, and others.
3–11
Differences in the prevalence of PH, causes, pathobiology, and response to treatment
may exist between the developed and developing worlds; hence, it is vital to address
these issues directly in the developing countries and not to extrapolate it from the
Western literature.
The initiative of addressing the challenges in managing PH in the DW came from recent
work between the Pulmonary Vascular Research Institute (PVRI) and the Aswan Heart
Center.
12
The purpose of this article is to address the issue of PH in the DW as a whole and
not to provide a specific solution in every single country. We shall explore the prevalence
of the PH, address the challenges of PH management, and give practical advice on how
to overcome these challenges in the DW. By doing so, we hope to increase awareness,
develop successful networks, and help in initiating training and educational programmes
for local physicians and medical staff, identifying and establishing local centres
of excellence.
All efforts were made to develop this document in an easy-to-read form, making it
handy and helpful to clinicians dealing with PH patients in the DW.
Acknowledging the lack of direct evidence in many recommendations, it is important
to reemphasize that this statement is not meant to substitute for international clinical
guidelines or the clinicians’ experience or decision.
Definition of pulmonary hypertension
Pulmonary hypertension is a hemodynamic and pathophysiological state and not a disease
per se.
13
It has been shown to be associated with, and caused by, various clinical conditions
that may or may not share similar histological and pathophysiological abnormalities.
According to the international guidelines,
14
PH is classified in to five groups based on similar mechanism, histopathology, clinical
pheno- and endo-typing, and response to therapy (Table 1).
10.7717/gcsp.202014/table-1
Table 1
Updated clinical classification of pulmonary hypertension (PH).
1 Pulmonary arterial hypertension (PAH)
1.1 Idiopathic PAH
1.2 Heritable PAH
1.3 Drug- and toxin-induced PAH
1.4 PAH associated with:
1.4.1 Connective tissue disease
1.4.2 HIV infection
1.4.3 Portal hypertension
1.4.4 Congenital heart disease
1.4.5 Schistosomiasis
1.5 PAH long-term responders to calcium channel blockers
1.6 PAH with overt features of venous/capillaries (PVOD/PCH) involvement
1.7 Persistent PH of the newborn syndrome
2 PH due to left heart disease
2.1 PH due to heart failure with preserved LVEF
2.2 PH due to heart failure with reduced LVEF
2.3 Valvular heart disease
2.4 Congenital/acquired cardiovascular conditions leading to post-capillary PH
3 PH due to lung diseases and/or hypoxia
3.1 Obstructive lung disease
3.2 Restrictive lung disease
3.3 Other lung disease with mixed restrictive/obstructive pattern
3.4 Hypoxia without lung disease
3.5 Developmental lung disorders
4 PH due to pulmonary artery obstructions
4.1 Chronic thromboembolic PH
4.2 Other pulmonary artery obstructions
5 PH with unclear and/or multifactorial mechanisms
5.1 Hematological disorders
5.2 Systemic and metabolic disorders
5.3 Others
5.4 Complex congenital heart disease
PH is generally defined as a mean pulmonary arterial pressure (mPAP) ≥25 mmHg (this
definition will probably be changed soon to >20 mmHg) at rest as assessed by right
heart catheterization (RHC).
13
This creates a real problem in the DW because RHC facilities are extremely limited
or not available in many situations mandating the need for alternative diagnostic
tool. Other hemodynamic values such as pulmonary vascular resistance (PVR), pulmonary
artery wedge pressure (PAWP), or cardiac output (CO) are not part of the general definition
of PH but are used to subclassify the disease (Table 2). These parameters are also
used to characterize the disease, assess severity and response to treatment, or as
prognostic measures in managing PH patients.
10.7717/gcsp.202014/table-2
Table 2
Hemodynamic definitions of pulmonary hypertension (PH).
Definitions
Characteristics
Clinical groups#
Pre-capillary PH
mPAP > 25 mmHg PAWP ⩽ 15 mmHg PVR ⩾ 3 WU
1, 3, 4 and 5
Isolated post-capillary PH (IpcPH)
mPAP > 25 mmHg PAWP > 15 mmHg PVR < 3 WU
2 and 5
Combined pre- and post-capillary PH (CpcPH)
mPAP > 25 mmHg PAWP > 15 mmHg PVR ⩾ 3 WU
2 and 5
For the sake of this document, PH will also be defined as right ventricular systolic
pressure (RVSP) >35 mmHg on transthoracic echocardiography (ECHO) in the absence of
pulmonary stenosis and acute right heart failure (RHF). PH severity is further defined
as mild if RVSP is 36–50 mmHg, moderate if RVSP is 51–60 mmHg, and severe if RVSP
is >60 mmHg. Subclassification of PH into one the five known subgroups using echocardiography
is more challenging, hence, RHC should always be done, whenever available.
Prevalence of pulmonary hypertension in the developing world
With the exception of a handful of recent registries from Africa and the Middle East,
the epidemiology of PH in the DW and the distribution of its etiologies are still
largely unknown. Limited reports suggest that the incidence of PH in the DW might
be higher than that reported in developed countries because of the prevalence of many
conditions that are considered as risk factors for PH such as HIV, hemolytic anemias,
schistosomiasis, rheumatic and congenital heart diseases, pulmonary tuberculosis and
subsequent lung damage, chronic viral hepatitis and others.
15–19
In the recent years there has been an increasing awareness of PH in the DW.
20
This applies to the recent recognition of the importance of PH as a primary disease
and as a poor prognostic marker for many other diseases. Unfortunately, the exact
estimation of PH prevalence is very difficult in the DW because of extraordinary socio-cultural,
ethnical differences, geographic and economic diversity, and substantial regional
variations in human development and health care infrastructure. Nevertheless, some
data has been published looking at different angles of PH.
Rheumatic heart disease (RHD) remains as one of the common causes of PH in the DW
but not in the developed world. Also, it has been estimated that around 33 million
patients are currently living with HIV/AIDS, most of them are in DW,
21
and about 0.5% of them might develop PH.
22,23
Similarly, schistosomiasis is highly prevalent in Brazil, North Africa, and the Middle
East, with an estimation that more than 200 million individuals are infected with
this parasite. In one study from Brazil, 30% of pulmonary arterial hypertension (PAH)
was caused by schistosomiasis.
24,25
Finally, an estimated 30 million people suffer from hemoglobinopathies worldwide,
most of them reside in the DW. Nearly 10% of this patient population might expect
to develop PH.
26
In Africa, the largest study on PH/RHF showed 697 (28%) of the 2505 patients presented
with de novo heart failure were diagnosed with PH/RHF between 2006 and 2008.
18
PH/RHF was the primary diagnosis in 50% of those patients. Most patients presented
clinically with dyspnea and found to have a mean RVSP >50 mmHg. Left heart disease
(31%), chronic lung disease due to chronic obstructive pulmonary disease and tuberculosis
(26%), and PAH (20%) due to HIV, congenital heart diseases (CHD) or idiopathic PAH
(IPAH) were the most common causes of PH.
Another study described the prevalence of PH in patients with RHD at a tertiary centre
in Nigeria.
27
Of 1312 ECHO studies, 10% had evidence of rheumatic heart diseases (RHD) and secondary
PH was present in 80% of those patients. Another African study found that hypertensive
heart disease (25%), peripartum cardiomyopathy (25%), dilated cardiomyopathy (17%)
and RHD (13%) are the most common causes of PH.
28
A similar study from Uganda showed a prevalence of PH in 309 patients presented with
newly diagnosed RHD of 33%.
29
A smaller survey from Lagos, Nigeria, investigated reported a 1% prevalence of PAH
in HIV patients presented with cardiovascular diseases.
30
However, PH with (RVSP > 30 mmHg) was present in 4% of long-term survivors of vertically
acquired HIV infection in Zimbabwe.
31
On the other hand, a screening study of patients with sickle-cell disease (SCD) in
Nigeria showed a PH prevalence of 25%,
32
while a study from Egypt indicates that patients with β-thalassemia might be at increased
risk of PH.
33
Finally, a study from Sudan described 14 consecutive cases of PH with previously treated
pulmonary TB.
34
The Pan African Pulmonary hypertension Cohort (PAPUCO) study is an African registry
20
and is discussed in detail elsewhere in this special issue by Mocombi et al.
The Egyptian collaborative PH registry has included 260 patients since 2016 with either
PAH (190, 73%) or CTEPH (70, 27%) diagnosed with RHC. Patients with congenital heart
disease were excluded. The mean age was 35 (±12) years and 69% were females. The mean
duration between symptom onset and a proper diagnosis was 39 (±13) months. Most of
the patients were already in WHO functional class III or IV at the time of enrollment
with a mean 6 MWD of 306(± 120) meters. 81 patients had CMR at the time of enrollment
with a mean RVEF 36% (± 13.5%). The most common subgroup of PAH was IPAH (62%). Acute
vasoreactivity testing was performed in 139 patients; Only 6% showed positive acute
vasoreactivity. PAH-CTD represented only (7%) of PAH patients, however, it could be
attributed to referral bias. Only 1% of PAH patients had schistosomiasis. Although
most of the patients had advanced disease, only 37% were receiving combination PH-specific
therapy at the time of enrollment. Patients with CTEPH were relatively young compared
to other registries (mean age was 37 (±10) years). Previous VTE was documented only
in 51% of CTEPH patients. 44% of of them underwent pulmonary endarterectomy.
In a hospital-based study from India, a CHD prevalence of 4/1000 live births has been
reported, with PDA and VSD being the most common lesions.
35
A similar prevalence rate was reported by many other population-based studies in the
same country.
36–39
It has been estimated that approximately 200,000 infants with CHD are born every year
in India,
40
and another 40,000 cases are diagnosed during childhood.
41
Furthermore, it has been estimated that 3–10% of infant mortality in India is attributed
directly to CHD.
40
Presently, only 2–3% of infants born with CHD receive timely attention for surgical
correction, while the vast majority of the remaining CHD population either fails to
survive beyond early childhood or develops irreversible pulmonary vascular disease.
At present, 24% of all cardiology admissions in India are related to CHD.
42
Schistosomiasis is a major health concern in many countries in the Middle East, Africa,
China, and Latin American countries, especially Brazil.
43–50
In a single center at the north-eastern region of Brazil, schistosomiasis was the
most prevalent etiology (39%), followed by PAH-CHD (26.9%), IPAH (14.6%), and PAH-CTD
(12.2%).
51
In China, it has been estimated that there are 2,500 to 5,000 new IPAH patients each
year and a much higher number for other forms of PH.
52
In Iran, the IPAH registry was opened in November 2009. One hundred and sixteen patients
(82 females, 34 males) were included. The mean age was 36.69 ±14 years. Of those,
approximately 8% were in New York Heart Association (NYHA) functional class IV, 53%
class III, 37% class II and 2% class I. Dyspnea on exertion was the most common symptoms
(98%), followed by extreme fatigue (92%), chest pain (56%) and syncope (34%).
53
Finally, a report of 107 incident PAH patients (diagnosed by RHC) in Saudi Arabia
was published.
54
The mean age at diagnosis was 36 (±9) years, with a female preponderance of 62.6%.
The mean duration between symptom onset and diagnosis was unacceptably long (27.8
± 9.0 months). As a result, 72.8% of the patients were in functional class III or
IV at presentation. IPAH was the most common subtype of PAH. CHD was the second most
common PAH subgroup and had the best physiological parameters compared to other groups.
Such high prevalence of PAH-CHD in Saudi Arabia probably reflects the current practice
of late detection of CHD patients and delayed surgical corrections. Systemic sclerosis
(SSc) was the leading cause of PAH-CTD. Heritable and portopulmonary PAH were the
least common causes and had the worse outcome. None of the patients tested positive
for schistosoma serology, however, this might be attributed to detection or referral
bias. Only 5 patients (4.7%) were candidate to use calcium channel blockers based
on reversibility testing. Thirty-one patients (28.9%) died during the 3-year follow
up period.
55
Another report from Saudi Arabia described the distribution of PH in 112 patients
diagnosed by RHC found that 10.7% belonged to PAH, 6% to PH due to left heart disease,
65% to PH due to lung diseases, 3.5% to chronic thromboembolic PH (CTEPH), and 14.2%
related to WHO group V diseases.
56
However, this center is recognised as the national center of interstitial lung disease
and referral bias can explain the high prevalence of PH due to lung disease in this
cohort.
Challenges for PH management in the developing world
1. Challenges in clinical diagnosis
The median duration of symptoms before establishing the diagnosis in the developed
world is more than two years.
57–59
In developing countries with limited access to adequate health care services, the
duration of symptoms is likely to be much longer.
54
In many situations, both the patients and the physicians tend to miss the diagnosis,
especially with the paucity and subtlety of physical signs in early disease. Breathlessness
is often attributed to other causes like asthma or even considered psychogenic in
origin. Syncope is often considered to be neurogenic or psychogenic. Cultural beliefs
and practices, as well as socio-economic factors may delay medical consultation. Physicians
with limited awareness and facilities to investigate may further add to the problem.
The financial burden may also force some patients to go towards traditional cheaper
approach and further delay the diagnosis. Lastly, governmental healthcare providers
may often have little interest in supporting PH related educational and treatment
programs as the disease is still considered rare, especially if the country is experiencing
other large-scale health threats.
2. Challenges in diagnostic evaluation
Initial evaluation
Although that both ECG and CXR might be abnormal in advanced disease, they are usually
not specific in early stages.
Echocardiography
Two-dimensional (2D)-echocardiogram can be an ideal screening tool but has its own
limitations as a diagnostic strategy,
13
as the findings may be subtle in early disease and an inexperienced operator can easily
miss the diagnosis on routine echocardiography exam. Under- or over-diagnosis of PH
is possible and is troublesome.
60
Furthermore, echocardiography has its limitation in identifying a specific cause or
differentiating between different groups of PH (e.g., pulmonary arterial hypertension
(PAH) versus heart failure with preserved ejection fraction (HFpEF). Also, echocardiography
cannot provide reliable values for pulmonary vascular resistance (PVR), pulmonary
artery wedge pressure (PAWP) or cardiac output (CO).
61–67
Nevertheless, Doppler echocardiography proved to be a reliable method for the estimation
of sPAP, being well suited to establish the non-invasive diagnosis of PH in patients
with cardiac diseases.
68
The estimation of sPAP has shown a good correlation with RHC and is based on the peak
velocity of the jet of tricuspid regurgitation. Despite its limitations, echocardiography
is not readily available in many centers within the DW.
Right heart catheterization
Right heart catheterization is the gold standard tool to diagnose PH and should always
be for this purpose, whenever available.
13
The safety of this procedure in experienced hands has been well established.
69
RHC is only available in a very few centers in the DW. Availability and cost are the
important considerations in many developing countries where resources are limited.
Furthermore, lack of experience and unfounded fear of complications are other reasons
for avoiding RHC.
3. Challenges in medical therapy
In many developing countries, PAH-specific therapy is considered too expensive and
not readily available. For economic restrictions, insurance and governmental agencies
may not be able to sponsor or reimburse the costs of the medications. Unfortunately,
despite high demand, major drug companies are not currently interested in these poor
markets, and it seems there are no plans in the near future to reduce the cost for
PH patients in these countries. On many occasions, generic medications are partially
available and are commonly used at sub-optimal doses to save money. Some physicians
mistakenly treat right heart failure due to PH with beta-blockers and angiotensin
converting enzyme inhibitors in a similar way they treat left heart failure. Other
physicians use calcium channel blocker as empiric therapy without RHC study or determining
the vasoreactivity. Both can be detrimental to the patients and raise again the inadequate
knowledge and awareness of the disease among health care providers.
4. Challenges in surgical treatment
Lung transplantation is not available in most DW (with a few exceptions, such as India
and Saudi Arabia). The facilities and expertise for pulmonary endarterectomy are not
available in most countries of the DW. Development of facilities for these procedures
is complex and beyond the physicians’ domain.
The authors recommend six main strategies/phases to overcome these challenges. However,
these phases may run in parallel in certain situation and not necessarily sequential.
Phase I: Collecting data and establishing the infrastructure
The idea is not to provide a formal registry, but rather to provide some form of a
data collection concerning the disease from both active patients and the patients-at
risk. A standard database format may be established by the PVRI via a specific taskforce.
This taskforce should liaise with health care providers and the responsible authorities
in the developing countries/regions and monitor work progress. It is recommended for
this database to be available online, whenever applicable, to facilitate data sharing
between centres in the DW and the PVRI taskforce. We might also look towards the PAPUCO
experience as a possible example for this database. The PAPUCO project originated
in South Africa and involved different countries on the continent and has overall
been very successful.
20
As different developing countries might have different health care systems, economic
power and/or specific needs, creating a regional map that categorizes each country
into specific sections/zones might be necessary. Therefore, as previously outlined,
a later stage of the project will include developing of the PVRI consensus statement
for establishing country’s specific guidelines in order to meet the needs of each
country/zone. This can be achieved by having multiple small cross-sectional surveys
in different regions of the DW.
Phase II: Education
The educational process has many tasks that include:
Specific awareness: The core of the educational task is to establish the specific
awareness plan for each country, to support the selection of the different leaders
in each country/zone, and to provide an extensive training program for the leaders.
This includes establishing specific “masterclass” courses and various PH symposia
designed to educate the individual country/zone leaders. The courses and symposia
should be facilitated by experts in the field and organised by the assigned taskforce.
The establishment of the Saudi Association of Pulmonary hypertension and its great
success in promoting awareness and education of different aspects of PH in the Arab
countries can be used as a role model to be used in other countries in the DW.
70–86
General awareness: This is usually achieved by running many awareness days and workshops
that include general knowledge about the presentation of the disease, risk factors,
and prognosis. It should also include the referral mechanism. This activity should
be adjusted to suit physicians (both specialized and general), nurses, patients, media,
and authorities. The PVRI can help by producing a generic template for a leaflet/booklet,
which can then be further detailed adhering to the needs of the specific country/region.
Maintaining awareness is key for success: The message should be consistent and repetitive
via continuous training for different ranks of doctors (junior and senior doctors
alike), nurses, and other healthcare providers.
Establishing telemedicine and teleconferences program and virtual consultation service
with experts in the PVRI.
Holding annual regional PH symposia to share experience. World experts should be invited
to these symposia to disseminate knowledge and information. They may also be involved
in direct patient consultation.
Phase III: Centers of Excellence
Creating the ‘centres of excellence’ for each country/region is of great importance
to take this project to a higher level. These centres are to serve for both management
and training. Specific country/region-based criteria should be developed for each
region. A measure for PVRI-accreditation system for these centres should be established
to ensure quality.
These centres may provide following tasks:
•
Establishment of referral criteria
•
Basic diagnostic tools (CXR, ECG, ECHO, CT scan, PFT lab)
•
Able to perform or refer patients for RHC
•
Cardiology and pulmonary services
•
Medical intensive care services
•
Basic research facility to help PH researchers in their own countries, and to put
them in touch with the centres of excellence in the developed countries.
A research project may be addressed in these settings which could prove very useful
to that particular country/region; e.g., high-altitude PH or PH secondary to infectious
diseases. Contributing to phase III international clinical trials may also be possible
in selected centres.
However, in some developing countries with very limited resources it might be more
practical to establish “centres of experience”, where all new PH patients should be
referred to in order to build adequate clinical experiences. The criteria for such
centers are:
•
Establishment of referral criteria
•
Basic diagnostic tools (CXR, ECG, ECHO)
•
Cardiology and pulmonary services
•
Medical intensive care services
Phase IV: Diagnostic and treatment algorithms
Development of “unique” diagnostic and treatment algorithms based on realistic situations
and available resources. Such algorithms should include the minimal acceptable criteria
to suite all developing countries and should be amended by each country/region to
meet its needs. These algorithms might not be evidence-based at the early stage and
might include many “expert opinion” recommendations. However, in future, these recommendations
should be validated based on real data obtained from each country.
Phase V: Funding:
Certainly, this is the cornerstone of the project. Fundraising should be tried on
many levels and should include:
•
Local fundraising
•
Involving local governments and authorities
•
Directing drug companies to the DW’s “market”
•
International charity programs
•
PVRI direct funding for certain research projects
The fund should be directed towards different fields that include:
•
Purchasing basic equipment to the peripheral clinic, which serve as the potential
case-finding. Such equipment may include CXR and ECG machines. More sophisticated
equipment such as ECHO, V/Q scanner, CT scan, cardiac catheters, etc. are also needed
in the selected centres of excellence
•
Sponsoring educational activities, such as the awareness courses, the masterclasses,
international symposia, public awareness and media coverage
•
Help in funding the medication (the presence of generic alternatives might help in
reducing the cost in these countries).
Phase VI: Patient associations
Although this is not a formal PVRI task, it is still recommended that the final consensus
paper should indicate the basic points of reference to set up patients’ associations
in specific countries/regions. This is important as it will help with future fundraising,
case studies, and promotional materials.
In conclusion, the aim of this project is to improve the field of PH management in
the DW, acknowledging the difficulties and the challenges mentioned in this paper.
The effort should be focused on the work for improving awareness and education, collecting
date, and establishing of regional referral centers, and to optimize resources to
give the best evidence-based medicine with better patient outcomes. The problems facing
the management of PH in the DW may be summarized as:
10.7717/gcsp.202014/table-3
Table 3
Recommendation for clinical evaluation (all patients).
Recommendation
Class of recommendation
Level of Evidence
Detailed history has to be obtained in all patients to understand the nature and severity
of symptoms.
I
C
WHO Functional class of the patients’ symptoms has to be established.
I
C
Meticulous clinical examination has to be done in all patients to establish the diagnosis
of PAH.
I
C
Diligent search should be made in history and examination to rule out secondary causes
of PH
I
C
All patients with PH should have a baseline 6MWT done.
I
C
All patients with PH should have a baseline ECG
I
C
All patients with PH should have a baseline CXR
I
C
Notes.
WHO FC
world health organization functional class
PH
pulmonary hypertension
6MWT
six-minute walk test
ECG
electrocardiogram
CXR
chest X ray
10.7717/gcsp.202014/table-4
Table 4
Echocardiography protocol for the diagnosis of pulmonary hypertension (if available).
Parameters
Comments
Assess LV systolic & diastolic function
Rule out group 2 diseases
Assess MV & AV structure and function
Rule out rheumatic heart disease
Assess LA dimensions & area
Central or rightward position of the inter-atrial septum indicates a left atrial pressure
higher than or equal to the right atrial pressure and makes the diagnosis of PAH less
likely.
Assess RV & RA dimensions and function
∘ RV free wall thickness ∘ RV dimensions ∘ RA volume index ∘ TAPSEo Tei index
Assess PV & TV structure and function
Rule out RHD
Exclude RVOT obstruction
PS [valvular /sub-valvular]
Measure TR
Best possible jet/Doppler alignment, use contrast if necessary
To assess for intra-cardiac shunts
Use contrast if needed
IVC collapsibility
For the estimation of RAP
Notes.
LV
left ventricle
MV
mitral valve
AV
aortic valve
LA
left atrium
RV
right ventricle
RA
right atrium
PV
pulmonary valve
TV
tricuspid valve
RVOT
right ventricular outflow tract
TR
tricuspid regurgitation
IVC
inferior vana cava
PAH
pulmonary arterial hypertension
TAPSE
Tricuspid annular plain systolic excursion
RHD
rheumatic heart disease
PS
pulmonary stenosis
RAP
right atrial pressure
10.7717/gcsp.202014/table-5
Table 5
Echocardiographic criteria for screening of high-risk patients for pulmonary hypertension,
if available.
Likelihood for PH
Criteria
Level of Evidence
PH unlikely
TRV ≤ 2.8 m/s, and sPAP ≤ 35 mmHg, and No additional echocardiographic criteria for
PH, and Asymptomatic
B
PH possible
Criteria A
• TRV ≤ 2.8 m/s, and • sPAP ≤ 35 mmHg, and
C
• Presence of additional echocardiographic criteria for PH, or symptoms suggestive
for PH
Criteria B
• TRV 2.9 - 3.4 m/s, or • sPAP 36 - 45 mmHg
C
PH likely
• TRV > 3.4 m/s, or • sPAP > 45 mmHg
B
Notes.
PH
pulmonary hypertension
TRV
tricuspid regurgitation jet velocity
sPAP
systolic pulmonary artery pressure
RHC
right heart catheterization
PAH
pulmonary arterial hypertension. (Modified from Idrees et al, with permission).
70
10.7717/gcsp.202014/table-6
Table 6
Hemodynamic parameters measured during RHC, if available.
Parameter
Class of recommendation
Remarks
RAP
I
CO/CI
IIa (see remarks)
By thermodilution (or by the Fick method in cases of systemic-to-pulmonary shunts)
MvO
2
%
IIa
PVR
I
Needed for the diagnosis of PAH
mPAP
See remarks
For diagnostic purpose: Class of recommendation I
For prognostic purpose: Class of recommendation IIb
PAWP
I (see remarks)
In case of inaccurate wedging, LVEDP should be measured
Vasoreactivity
See remarks
Class of recommendation I in IPAH
Class of recommendation IIa in CHD-PAH and CTEPH
Class of recommendation IIb in other forms of PH
Notes.
RAP
right atrial pressure
CO/CI
cardiac output/cardiac index
MvO2%
mixed venous oxygen saturation
PVR
pulmonary vascular resistance
mPAP
mean pulmonary artery pressure
PAWP
pulmonary artery wedge pressure
1.
The size of the problem: Very limited data is available on the prevalence and the
extent of the problem in the DW. However, it is likely that the magnitude of the problem
might be enormous given that many diseases known to be associated with PH, such as
uncorrected congenital heart diseases, schistosomiasis, HIV, rheumatic heart diseases,
hemolytic anemia, and parenchymal and chronic pulmonary airway disease are prevalent
in developing countries.
2.
Different developing countries might have different problems, needs, and resources,
and so local guidelines should be established to meet the basic or minimal criteria
needed to build a clinically meaningful PH program.
3.
There are potential differences in etiology of PH between developing and developed
countries. Epidemiological data regarding PH and disease-specific registry data is
available from many developed countries but not from developing countries. The spectrum
of the diseases causing PH is likely to be different between the developed and developing
worlds. PH due to CHD, RHD, schistosomiasis, hemolytic diseases, and HIV infection
are more important causes for PH in the developing countries, but they are much less
common in the developed countries where biological research or drug development takes
place. Furthermore, clinical trials done to test new drugs may exclude the typical
PH patients of the developing countries. By extrapolation, PAH-specific drugs are
used in these conditions, though their efficacy cannot be certain.
4.
Poor awareness about the disease and its burdens between patients, health care providers,
and the authorities
5.
One of the most difficult problems to overcome is the weak economic power, which is
present in most developing countries, and the absence of the basic infrastructure
and medical resources required to diagnose and treat PH patients. Such economic challenges
make recommendations concerning evidence-based diagnostic algorithm given by international
(Western) guidelines unrealistic and inapplicable. The authors have suggested general
recommendation concerning diagnosis and management of PH in the DW (Tables 3–6).
6.
The controversy about the ownership of PH project can be a major issue that may halt
the whole project. In many developing countries, certain parties try to own such projects
to gain power, including political, financial or medical. Hence, it is very important
to keep the administrative process of this project under the PVRI, who should collaborate
with certain “representatives”/task leaders in each country/region.
The way forward
There are many knowledgeable and competent physicians in the developing countries,
who are interested in PH management. They should work together in their respective
regions and strive to educate the other physicians in early diagnosis of PH. A global
project is urgently needed in order to improve the outcome of PH in the DW, acknowledging
the difficulties and the challenges mentioned in this paper.
The international institutes, such as the PVTI, should work with the local initiatives
in the DW to improve awareness and education, collecting data, establishing regional
referral centers, and focusing on optimizing resources in order to build collaborative
PH programs in the DW.