Journal Reading

Pulmonary hypertension
in chronic heart failure:
definitions, advances,
and unanswered issues
Oleh:
dr.
Introduction
Heart failure (HF)
• 23 million individuals worldwide.
• prognosis of HF remains poor
• Pulmonary hypertension (PH)  unfavourable outcome in chronic HF (CHF)

Mechanism of PH in HF
• Pulmonary vascular congestion due to increased pulmonary venous pressure
• Pulmonary arterial vasoconstriction and remodelling associated with increased
pulmonary vascular resistances (PVR)
 Chronic PH induces right ventricular (RV) remodelling  RV failure

elevated PVR  contraindication to heart transplantation 

Late Stage of HF
RV graft failure

no study has demonstrated the efficacy of any treatment

STUDY AIM
• report the evolution of the concepts on post ‐capillary PH (diagnosis, prevalence,
prognosis, and therapeutics).

 link between structural alterations and haemodynamic abnormalities

 possible reasons for treatment failures
 future potential targets.
How is/was post‐capillary pulmonary
hypertension defined in heart failure
and why did pulmonary hypertension
definition change over the last 10
years?
 Pulmonary hypertension
increase in the resting mean pulmonary artery pressure (mPAP) ≥ 25 mmHg
measured by right heart catheterization (RHC).

Post‐capillary PH
mPAP ≥ 25 mmHg and a pulmonary arterial wedge pressure (PAWP) > 15 mmHg.
Changes in pulmonary hypertension definitions over time
 Do the various definitions of post‐
capillary pulmonary hypertension in
chronic heart failure meet their
objectives?
Impact of post‐capillary pulmonary hypertension definitions on the
pathophysiological understanding of the disease

Definitions proposed for Group 2 PH

• Based on invasive haemodynamic measurements
• do not include an anatomical characterization of the pulmonary vasculature

close and proportional relationship

Studies between the vascular remodelling and Limited in HF
haemodynamic measurements
 Delgado and colleagues

• vascular lesions in pulmonary arteries of 17 heart transplant recipients

with preoperative PH who died shortly after transplantation

medial hypertrophy of pulmonary arterioles  common, severe, and constantly present

limits of haemodynamic measurements to characterize pulmonary arteriolar remodelling in CHF

Gerges study

• nine patients with elevated TPG/elevated DPG, compared with the

nine other patients with elevated TPG/normal DPG

elevated DPG  identify pulmonary arteriolar remodelling.

 limited
difficulties to
number of
investigate limited
patients weakened
pulmonary availability
this study with the
vascular of lung
available conclusions
remodelling samples.
pulmonary
in CHF
histology

Most elevation in PVR

resolves relatively quickly after left

ventricular assist device (LVAD)
placement
the current definitions may overstate
combined post‐capillary and pre‐ the value of haemodynamic
capillary PH (Cpc‐PH) or fixed parameters that is not really proven
remodelling

relatively uncommon
Supposed mechanisms of combined pulmonary hypertension in
chronic heart failure current

LA, left atrial; mPAP, mean pulmonary artery pressure.

 • Which genetic, biochemical, and environmental factors may
sigificantly impact PH development by modifying NO availability,
endothelin expression, collagen deposition, and other mechanisms
involved in pulmonary arteriolar dysfunction and remodelling?

• Are there substantial structural and functional differences between

pulmonary arteriolar remodelling and PH in HF with reduced left
ventricular ejection fraction, HF with preserved left ventricular
ejection fraction (HFpEF), or mitral stenosis?
Several other
questions remain: • What is the time course of pulmonary arteriolar remodelling in the
different left‐heart diseases?

• Which PH phenotype is associated with reversible pulmonary

arteriolar remodelling, and how do we measure reversibility? It is a
clinically relevant problem and a very controversial issue in the
literature (Which drugs are used in vasodilator challenge? Which
doses? What are the haemodynamic objectives of these tests? etc.);
furthermore, it is unknown whether the vasodilator challenge has a
clinical or prognostic significance in the general population of HF
patients.
 pulmonary arteriolar secondarily to chronically elevated
‘vascular theory’
vasoconstriction and remodelling pressures in the left hear

RV distribution continuum ending with the left atrium, and the left atrial (LA) reservoir function is therefore a
system critical component of the total RV afterload

Blood entering in steep pressure rise and a prominent V wave, increasing the systolic PAP (sPAP).
a non‐compliant
left atrium

LA dysfunction major determinant of PH‐HF.

impaired echocardiographic LA‐strain response at exercise in HF patients  haemodynamic

trigger for RV–pulmonary artery (RV–PA) uncoupling and exercise ventilation inefficiency. 35
RV dysfunction is common in HF and that its presence
contributes to increased morbidity and mortality RV
distribution system.

poor prognosis in PH‐HF  detrimental consequence that

PH exerts on the right ventricle.

that right heart afterload alone is not poorly prognostic

RV coupling to the right heart afterload and pulsatile load

at rest and at exercise

the main determinant of the course of the disease. 31

Impact of post‐capillary pulmonary hypertension definitions on disease
prevalence and prognosis

Definitions proposed for Group 2 PH

• Based on invasive haemodynamic measurements
• do not include an anatomical characterization of the pulmonary vasculature

close and proportional relationship

Studies between the vascular remodelling and Limited in HF
haemodynamic measurements

prevalence of 12% and 38% in HF patients

increased DPG
Relationship between commonly used haemodynamic parameters and various issues in
post‐capillary pulmonary hypertension
Many studies  PH in HF is a marker of poor outcome  several factors
interfere with the assessment of PH‐HF

1 • haemodynamic parameters measured by RHC, including PAP, are dependent on

blood pressure, cardiac function (CO, LV, and RV function), and blood volume

2 • neither the TPG nor the DPG has clearly shown any incremental prognostic value
(rehospitalization and cardiovascular death

3 • PVC and PVRs seem to be the two most interesting parameters  strongly
related to the CO  cannot be interpreted independently.

4 • unclear how PH definition truly impacts prognosis.

Which parameter is important for the treatment of heart failure and
pulmonary hypertension?

MEDICAL INTERVENTIONS
• based on blood volume optimization with diuretics and sodium and fluid restriction
• addition to the optimal medical treatment of HF.

specific therapeutic targets  control of

Last the pulmonary arteriolar tone and the Inconsistent
Decades alveolo‐capillary membrane results
permeability
SIOVAC trial results

• worse outcomes with sildenafil in patients with persistent PH after

correction of valvular disease.

MELODY‐1 trial

• Cpc‐PH, macitentan  frequent adverse events and fluid retention

• did not improve any exploratory endpoints
• harmful in WHO Group 2 PH

Clinical trial with PAH Theraphy

• Treatment failure  patients were not included on the basis of

haemodynamic definition of PH
 HEART TRANSPLANTATION AND LEFT VENTRICULAR ASSIST
DEVICES
• elevated PVR  contraindication to heart transplantation
• baseline PVR with or without reversibility test  post‐transplant survival

International Society perform RHC before heart

2016 for Heart and Lung transplantation in order to measure the
Transplantation mPAP and PVR
 increasing CO and
implanted LVADs in heart transplant
Several recent decreasing LV filling
severe PH and with reduced risk of
studies pressure, mPAP,
elevated PVR RV failure.
and PVR,

Most elevation in PVR resolved quickly after LVAD replacementy uncommon

PH‐HF shows a significant potential of reversibility. 49

diagnostic usefulness of combined PH‐HF markers (PVR, DPG, and TPG) remains limited

Predicting reversible pulmonary vascular damage remains a clinical challenge

Which questions should be answered
to improve pulmonary hypertension
management in heart failure?
 What would be the characteristics of an ideal pulmonary hypertension
marker?

IDEAL PH MARKER
• diagnosis, monitoring, and therapy
• differentiate between pre‐capillary and post‐capillary PH
• distinguish the mechanisms of post ‐capillary PH  therapeutic actions

Right heart invasive, and limited in

gold standard to define PH
catheterization HF clinical practice

• misdiagnosis or late diagnosis and also to a bias in PH prevalence estimation.

 Echo- commonly used and reliable
PAP
cardiography assessment

• Maximal velocity of the tricuspid regurgitation

• Evaluate RV dilation and function and explore left ‐side disease
• Vmax  60% cases

wireless PAP Implanted microelectron-

CardioMEMS
monitoring mechanical system‐based invasive
system PAP sensor during RHC
CT (dual‐
energy) or lung future the direct or indirect pulmonary vascular disease
perfusion MRI assessment

• dynamic contrast‐enhanced CT was able to distinguish patients with and without PH

 specificity and sensitivity of 100%
• MRI‐based 3D volumetry of central pulmonary artery measurement 
discriminate patients with or without PH
 Should pulmonary hypertension and pulmonary vascular remodelling
only be considered as detrimental in HF?

Vascular Remodelling And Vasoconstriction

• chronic increase in PH
• increase in LHFP that exceeds the ‘buffer’ capacity of the left atrium
• Pulmonary  prevent pulmonary oedema maintaining an effective CO.

poor prognosis  different primary cause  pathological

persistence of
hypervolemia mechanism from pre‐ remodelling of the pulmonary
capillary PH capillary
Physiopathologically, Preserve alveolo‐capillary
vascular remodelling, or haematosis and maintain Pulmonary vasodilation
vasoconstriction the right CO.

• Chronic increase in LAP • Pulmonary oedema.

major detrimental
‘alveolar
Vascular consequence that PH worse
protective
remodelling exerts on the right prognosis.
mechanism’
ventricle
 CONCLUSION
Pulmonary hypertension  important prognostic marker in CHF, and its precise prevalence
remains unknown.

The exact pathophysiology of PH in HF is still only partially understood.

RHC allows accurate measurement of mPAP and main pulmonary artery haemodynamic
parameters,

RHC limitations  changes in post‐capillary PH definition during the last decade 

complexity of identifying a good marker and surrogate of post ‐capillary PH.
 CONCLUSION
New therapeutics targeting pulmonary pressure/remodelling were inconclusive except
for the indisputable control of hypervolemia.

Further studies
• Whether post‐capillary PH is more a risk marker or a therapeutic target
• Identify a (biological, morphological, or haemodynamic) parameter that could better
characterize the adaptability of the circulatory system to face chronic pressure elevation
in CHF.

Studying RV coupling and LA functional capacity  promising approach.

 Does anyone have any
questions?
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