Right Heart Failure &

Pulmonary Hypertension

ქეთევან გაბრიაძე
Anatomy, Function and Dysfunction of the RV
The RV is 10-15% larger in volume than the LV, with thinner free wall
and smaller mass. With aging, there is a reduction in RV mass and
volume and an increase in ejection fraction (EF).  Three anatomic
components are often described:
1) the inlet, containing the tricuspid valve apparatus;
2) the trabeculated apex;
3) the outlet or infundibulum.

Although in the LV there are 3 distinct myocardial layers of

aggregated cardiomyocytes, there are only 2 in the RV:
1. a superficial, predominantly circumferential layer and
2. a subendocardial, predominantly longitudinal layer .

The RV and LV are closely interrelated, not only through the septum,
but also through shared epicardial circumferential myocytes and the
pericardial space, all of which constitute the anatomic basis for
biventricular interdependence.
 Etiologies of RV Pressure Overload, Volume Overload, and RV Cardiomyopathy
RV Pressure Overload
Pulmonary hypertension (PH)*
Pulmonary arterial hypertension
Due to left heart disease
Due to lung disease and/or hypoxia
Chronic thromboembolic PH and other
pulmonary artery (PA) obstructions
Unclear and/or multifactorial
mechanisms
Pulmonary valve stenosis
PA stenosis
Pulmonary embolism
 
 
 
RV Volume Overload RV Cardiomyopathy
Valvular regurgitation Myocardial infarction (MI)
Tricuspid Arrhythmogenic RV cardiomyopathy
Pulmonary Dilated cardiomyopathy
Systemic-to-pulmonary shunt Hypertrophic cardiomyopathy
Atrial septal defect Amyloidosis
Partial anomalous pulmonary vein Myocarditis
drainage
High output states** (i.e., thyrotoxicosis) Sarcoid
  Transplant
  Post-surgery
  Post left ventricular (LV) assist device
  Cardiotoxicity (i.e., chemotherapy)
  Sepsis
Abstract

Pulmonary hypertension (PH) is a feature of a variety of diseases and continues to

harbor high morbidity and mortality. The main consequence of PH is right-sided
heart failure which causes a complex clinical syndrome affecting multiple organ
systems including left heart, brain, kidneys, liver, gastrointestinal tract, skeletal
muscle, as well as the endocrine, immune, and autonomic systems. Interorgan
crosstalk and interdependent mechanisms include hemodynamic consequences such
as reduced organ perfusion and congestion as well as maladaptive neurohormonal
activation, oxidative stress, hormonal imbalance, and abnormal immune cell
signaling. 
In PH or pulmonary arterial hypertension (PAH), elevated pulmonary artery pressure
and pulmonary vascular resistance (PVR)—representing an increased right ventricle
(RV) afterload—lead to right heart strain and failure, which in turn also affects left
heart function. Both impaired perfusion caused by systemic low output and systemic
congestion caused by impaired RV function cause insult to numerous organ systems.
This leads to local liberation of soluble proinflammatory mediators, and thus initiation
of inflammatory cascades. This scenario is associated with systemic inflammation,
where locally liberated circulating proinflammatory cytokines act in a paracrine
fashion, but also affect other targets.CVP indicates central venous pressure; GI,
gastrointestinal; LMCS, left main compression syndrome; PA, pulmonary artery; and
RAP, right atrial pressure.
Classification of pulmonary hypertension
• 1.1. Idiopathic (IPAH)
• 1.2. Heritable
• 1.3. Drugs and toxins
• 1.4. Associated with:
• 1.4.1. Connective tissue disease
• 1.4.2. HIV infection
• 1.4.3. Portal hypertension
• 1.4.4. Congenital systemic-to-pulmonary shunts
• 1.4.5. Schistosomiasis
• 1’. Pulmonary veno-occlusive disease
• 1” Persistent pulmonary hypertension of the newborn
• 2. Pulmonary Hypertension Secondary to Left Heart Disease
• 2.1. Left ventricular systolic dysfunction
• 2.2. Left ventricular diastolic dysfunction
• 2.3. Left-sided valvular heart disease
• 3. Pulmonary Hypertension Associated with Lung Diseases and/or Hypoxaemia
• 3.1. Chronic obstructive pulmonary disease
• 3.2. Interstitial lung disease
• 3.3. Sleep-disordered breathing
• 3.4. Alveolar hypoventilation disorders
• 3.5. Chronic exposure to high altitude
• 3.6. Developmental abnormalities
• 4. Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
• 5. Miscellaneous
• 5.1. Haematological
• Chronic haemolytic anaemias, sickle cell, thalassaemia
• Myeloproliferative disorders
• Post-splenectomy
• 5.2. Systemic disorders e.g., sarcoidosis
• 5.3. Metabolic disorders a. thyroid disorders b. glycogen storage diseases c. Gaucher’s disease
• The commonest lung diseases are obstructive airway disease followed by lung
fibrosis. Another important cause which is frequently overlooked is obstructive
sleep apnoea (OSA). PH is present in 17-53% of individuals with OSA .Lung
diseases cause pulmonary hypertension via hypoxia which causes polycythaemia,
vasoconstriction and vascular remodelling, in addition to damage of lung
parenchyma with loss of vascular bed.
• A particular type of PH results from acute pulmonary embolism, and can result in
acute right heart failure as the RV fails to maintain blood flow past an obstructing
large embolus. Recurrent showers of smaller pulmonary emboli can end in chronic
thromboembolic pulmonary hypertension (CTEPH). Here emboli do not
completely resolve, but they partially recanalise and are endothelialised, resulting
in pulmonary artery obstruction.
• All congenital heart diseases with increased pulmonary blood flow, mainly left-to-
right shunts, can lead to PH. The development of PH depends on the duration of
exposure and its magnitude, i.e., ventricular septal defect and patent ductus
arteriosus (post-tricuspid defects) patients tend to develop PH earlier than atrial
septal defect patients (pre-tricuspid).
Pulmonary hypertension type 1 is idiopathic or secondary to connective tissue. Idiopathic PAH affects mostly females. It is
thought to be caused by an imbalance of vasodilator NO pathway and vasoconstriction endothelin-1 pathway. It is
characterised by increased pulmonary vascular resistance due to remodelling and occlusion of the pulmonary arterioles.

Less commonly, RV failure could result from direct affection of myocardial disease by myocarditis, cardiomyopathy,
ischaemia, or arrhythmia. Right ventricular infarction complicates 30–50% of inferior myocardial infarction and it is
usually caused by occlusion of the proximal right coronary artery. Compared with the left ventricle, the right ventricle is
more resilient in the face of ischaemia. This is due to less myocardial oxygen demand, coronary perfusion occurring
throughout the cardiac cycle, and a dual blood supply - the left anterior descending artery supplies the anterior two-
thirds of the septum. So, in the majority of cases, the RV recovers within a few days. However, during the initial
presentation profound hypotension and shock may be present.

The tricuspid valve is organically affected in rheumatic heart disease, in infective endocarditis in IV drug addicts, or by
trauma caused by pacemaker electrodes during implantation or retrieval. Ebstein’s anomaly frequently presents as right
heart failure in children or in early adulthood.
Clinical diagnosis
Symptoms of right heart failure are mainly due to systemic venous
congestion and/or low cardiac output. This includes:
• exertional dyspnoea
• Fatigue
• dizziness
• ankle swelling
• epigastric fullness and right upper abdominal discomfort or pain
Signs:
• raised jugular venous pulse (JVP),
• left parasternal lift,
• an accentuated second pulmonary sound,
• right ventricular gallop, usually a pansystolic murmur over the tricuspid area which
increases with inspiration, and sometimes diastolic murmur of pulmonary
insufficiency;
• an enlarged tender liver, ascites frequently present as well as ankle oedema.

 JVP- It is a specific sign of right heart failure and reflects raised right atrial pressure. It
correlates well with raised left heart filling pressure in LV failure. Raised JVP is a
prognostic marker. Kussmaul's sign, which is an increase of JVP on inspiration, can help
in pointing to the cause of RHF. It is caused by impaired RV diastolic compliance with
increased venous return, as seen in constrictive pericarditis and RV infarction.    
Right ventricular infarction should be suspected in the context of inferior MI by the triad
of raised JVP, hypotension and clear lung fields.
Technical clues to diagnosis

• Electrocardiography in patients with pulmonary hypertension shows

signs of RV hypertrophy in the form of right axis deviation, dominant R
in V1 and dominant S in V5 or 6 + P pulmonale. An elevated ST in V3R
and V4R denoting RV infarction is present in 50% of inferior MI.
• Echocardiography can give a rapid estimate of the RV size, shape and
shift of the IVS. An RV/LV basal diameter of more than 1 plus loss of
sphericity of the LV (the D sign) are taken as evidence of a rise in PAP.
Flattening of the septum occurs in diastole in volume overload: e.g. in
the shunts and in systole in pressure overload and in both systole and
diastole as the pressure rises more as in all advanced pulmonary
hypertension, including Eisenmenger’s syndrome.
Because of the RV geometry and the complex 3D shape, measurement of RV function is a challenge. Tricuspid annular plane systolic
excursion (TAPSE) is a rapid and reproducible parameter as it is a surrogate of the longitudinal fibres’ function. It measures the
tucking effect of the apex on the tricuspid annulus. It is not affected much by loading condition. It is angle-dependent. Longitudinal
displacement of 17 mm or less is indicative of poor RV function and poor prognosis.
Estimation of pulmonary hypertension is an integral part of evaluation of a patient with suspected RVF. PASP can be estimated non-
invasively in the absence of pulmonary stenosis by measuring the velocity of tricuspid regurgitation and applying the simplified
Bernoulli equation and JVP. In symptomatic patients, a peak tricuspid regurgitation velocity >2.8 m/s is consistent with the presence
of significant pulmonary hypertension.
Special attention should be paid to IVC diameter and distensibility in relation to respiration when examined in the subcostal view. A
distended IVC >21 mm with decreased inspiratory collapse points to the presence of pulmonary hypertension and denotes raised
right atrial pressure.
Examination of the PA and the flow across it gives a further clue for PH. As RV pressure increases, peak systolic velocity will occur
earlier in systole, resulting in a more triangular shape of the pulmonary flow envelope instead of the normal dome shape. Thus, a
value of less than 100 ms of PA acceleration time is regarded as indicative of PH. Also, a dilated PA >25 mm, especially if it is
associated with early diastolic pulmonary regurgitation >2.2 m/s, is another echocardiographic feature.
In constrictive pericarditis, because of the dissociation of intrathoracic and intracardiac pressures, there is a respiratory variation in
the peak flow velocity across the mitral valve. Thus, there is a drop of pressure in the pulmonary veins during inspiration but not in
the left atrium, resulting in a decrease of the normal gradient pressure responsible for LV filling. Consequently during inspiration,
there is a decrease in the initial E velocity on the transmitral flow velocity curve. During expiration, as the intrathoracic pressure
increases, the gradient of the pulmonary veins/left atrium is restored and is seen on echo as a pronounced increase in the initial E
velocity. In severe cases, a septal bounce can be visualised.
Contrast echo is useful in the detection of intracardiac shunts.
• A lung function test is needed when the diagnosis of cor pulmonale is contemplated to confirm the
presence and severity of obstructive airway disease. High-resolution CT of the chest is helpful when
underlying lung fibrosis is a possible diagnosis. Overnight oximetry is useful when sleep-breathing
disorders are suspected to demonstrate repeated episodes of desaturation from 10 to almost 40
sec with an anoxia/hypoxia index (AHI) of at least 15/hour, consistent with the diagnosis.
• Cardiac MRI is the gold standard nowadays for measurement of RV volumes and function. MRI
has the advantage of tissue characterisation which is useful in such conditions as arrythmogenic
right ventricular dysplasia or myocarditis. It is also useful in the diagnosis of congenital heart
diseases. Cardiac MRI, as well as CT, can detect pericardial thickening of more than 2 mm, which is
useful when constrictive pericarditis is considered.
• CT pulmonary angiography is essential if CTEPH is suspected. Typical CT features in CTEPH patients
include: asymmetric enlargement of central pulmonary arteries in contrast to other causes of
pulmonary hypertension, plus a variation of size in segmental arteries and a mosaic pattern of lung
parenchyma (areas of hyperattenuation and low attenuation). [10]
• Right heart catheterisation (RHC) is needed for the diagnosis of PAH and may also be needed in
constrictive pericarditis. PAH (pre-capillary) is defined by a high PAP above 25 mmHg with normal
wedge pressure <15 mmHg and increased pulmonary vascular resistance (>3 Wood units). In
constrictive pericarditis, there is an increase and equalisation of end pressure in all four chambers
plus a dynamic respiratory variation in LV and RV pressure tracings.
Biochemical markers

• Systemic venous congestion affects the liver and kidney and results in
derangement of their function. Raised transaminases and bilirubin plus
prolonged prothrombin time are common in right HF and reflect poor
prognosis. Raised renal chemistry is frequently noted and may improve with
diuretics.
• There are no specific biomarkers for right heart failure, but raised BNP and
troponins reflect stress and injury in different RHF scenarios. Their rise reflects
the severity of the condition and portends poor prognosis. For example,
Krüger has noted that BNP is elevated in acute pulmonary embolism
complicated by RV dysfunction, but is within normal range when RV function
is preserved. Patients with pulmonary embolism and plasma lactate level >2
mmol/L are at high risk of death and adverse outcome.
Diagnostic algorithm

A useful working algorithm in right heart failure is to establish the presence of PH or

another cause, mainly primary myocardial disease or pericardial disease. If a careful history-
taking – with a chest X-ray to reveal symptoms and signs, and an ECG – raise suspicion of PH
or RHF, then the next step is to perform transthoracic echo. Echo is useful in investigating LV
and RV systolic/diastolic function and valvular structure and will confirm the presence of
PH. At this stage, LVF as the commonest cause can be proven or refuted. If PH is present
and there is no significant LV dysfunction, then proceed to exclude the second commonest
– lung diseases. This includes lung function test, transfer factor and high-resolution CT, and
overnight oximetry if interstitial lung disease or OSA still needs to be excluded. If tests are
negative/inconclusive thus far, then a ventilation perfusion scan is the next step for CTEPH
exclusion. A positive V/Q scan necessitates CT pulmonary angiography for confirmation,
while a negative scan increases the probability of PAH type 1. RHC is needed in addition to
connective tissue disease screening, including antiphospholipid antibodies, HIV and a test
for schistosomiasis, if relevant.
Treatment
• Vasodilatator, Calcium channel blockers
• Prostaciclin analogy
• Endotelin receptors blockers
• Oxugen therapy
• Diuretics
• Anticoagulants
• Lung Trasplant
References
1. https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice
/Volume-14/Right-ventricular-failure
2. https://www.acc.org/latest-in-cardiology/articles/2020/01/21/08/4
6/anatomy-function-and-dysfunction-of-the-rv#:~:text=The%20Nor
mal%20RV&text=Three%20anatomic%20components%20are%20oft
en,3)%20the%20outlet%20or%20infundibulum
.
3. https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.1
16.022362#:~:text=The%20main%20consequence%20of%20PH,%2
C%20immune%2C%20and%20autonomic%20systems
.
4. https://pah.tv/ResourceCenter/TestingDiagnostics/ChestXRay.aspx
5. https://pubs.rsna.org/doi/full/10.1148/radiol.2018180603