Pulmonary HT in the cath lab –
practical and ideal
Antoinette Cilliers
Paediatric Cardiology
C.H. Baragwanath Academic Hospital
University of the Witwatersrand
Johannesburg
Pulmonary Hypertension
• mPA pressure ≥ 25 mmHg (n = 14 ± 3mmHg).
• or 30 mmHg with exercise.
Pulmonary Vascular Disease
•
•
•
•
mPA pressure ≥ 25 mmHg.
PCWP (estimate of LAmp) ≤ 15 mmHg.
PVR ≥ 3 Wood Units.
Transpulmonary pressure gradient (TPG) ≥ 12
mmHg.
Classification of PHT
5th World Symposium on PH, Nice, France, Feb 2013
• Pulmonary arterial hypertension - CHD.
• Pulmonary hypertension due to left heart
disease.
• Pulmonary hypertension due to lung disease
and or hypoxia.
• Chronic thromboembolic pulmonary
hypertension (CTEPH).
• Pulmonary hypertension with unclear
multifactorial mechanisms.
JACC 2013;62(25), Suppl D: D34-41
Levels of PHT
Right Heart
Pre-Capillary
PCWP normal (6-12 mmHg)
High PVR > 3 WU
Left Heart
Post-Capillary
PCWP > 15 mmHg
Normal PVR
High LAp, High LVEDP
PHT and CHD
D’Alto M. Eur Respir Rev 2012;21:328
• PHT is a frequent complication L > R shunts.
• Increased PBF and pressure may result in
vascular remodelling & endothelin dysfunction.
• Leads to increased PVR and eventually reversal
of the shunt or Eisenmengers syndrome (most
advanced form of PHT due to CHD).
• Definition of Eisenmengers syndrome (1897) PHT at systemic levels due to high PVR (>
800dynes sec/cm2 = Dr Wood) with reversed or
bidirectional blood flow through a septal defect.
PHT & CHD
• PHT starts at birth, progression depends on
type and size of defect.
• Some children do not develop severe PHT –
genetic predisposition ?
• Usually reversible < 1-2 years.
• Cyanotic Lesions develop PVD earlier < 6 mo,
hypoxia is a trigger for pulmonary
vasoconstriction, saturations > 85% indicate
operability in infants < 1yr of age.
Saxena A. PHT in CHD. PVRI 2009;2:101
Cyanosis in patient with large ASD
• Not necessarily due to irreversible PVD.
• May occur with normal pulmonary artery
pressures due to:
* Unroofed coronary sinus
* Very large defect e.g. common atrium
* Streaming of IVC blood to LA
Saxena A. PHT in CHD. PVRI 2009;2:101
Patients at high risk of PHT
Lopes AA et al. Pulm Circ 2014;4(2):330
• Age > 1-2 years.
• Cardiac anomaly viz:
* Truncus arteriosus
* AVSD
* TGV + VSD (see next slide)
• Large defects.
• Bidirectional shunts + periods of desaturation e.g
with exertion or feeding.
• Absence of heart failure.
• Downs Syndrome – recurrent LRTI, decreased alveolar
density and macroglossia causing chronic UAO, &
endothelin dysfunction.
Prevalence of PHT in patients with CHD
D’Alto M. Eur Respir Rev 2012;21:328
No technique is perfect for assessment of
operability in a borderline case …
• Comprehensive evaluation is necessary …
* Clinical evaluation(cyanosis, clubbing,
presence of murmur)
* CXR
* ECG
* ECHO
* Catheterization data
• It is possible to make the right decision in the
majority of cases.
Saxena A. PHT in CHD. PVRI 2009;2:101
Large VSD with PHT
OPERABLE
Cardiomegaly, prominent PA segment,
increased pulmonary vasculature,
pruning may occur.
Eisenmenger Syndrome
INOPERABLE
Smaller heart, prominent PA segment,
pruning.
Saxena A. PHT in CHD. PVRI 2009;2:101
ECG – operable VSD + PHT
Q wave present in V6, right axis, RVH
ECG – inoperable PDA + PHT
Q wave present in V1, right axis, poor LV forces in V6.
ECHO
Important for diagnosis of
lesion
* Direction of shunting can be seen
* Severity of PHT can be assessed
using TR and PR velocities
Cardiac catheterization – Gold Standard ?
BUT…………………………
Need for cardiac catheterization?
• Unnecessary in presence of overt pulmonary
congestion associated with left to right shunts
especially < 6 mo?
• Unnecessary in patients with Truncus arteriosus,
TGV + VSD, AVSD < 3 mo?
• Necessary in select patients > 6mo when there is
concern about irreversible PHT ?
• Univentricular hearts for Glenn, Fontan surgery.
• Children at high altitude < 3-6 mo ?
Lopes AA, Leary PW. Cardiol Young 2009;19(E-Suppl.1):8-12
Criteria for Closing Cardiac Shunts
WSPH of the WHO, Nice, France, Feb 2013
JACC 2013;62 (25), Suppl D:D34-41
PVR index ≥ 6 WU and PVR/SVR ratio ≥ 0.33 are at risk of developing PAH
late after shunt closure. D’Alto et al. Int J Cardiol 2013;168:3797
Assessment of PVR & SVR
several sources of error !
• Inappropriate haemodynamic and respiratory
conditions.
• Inadequate blood sampling and processing.
• Inappropriate assumptions and
approximations.
Resistance is the pressure drop across the
pulmonary or systemic circulation per unit
of flow in a specified time period = mmHg/L/min
or Wood units (u.m2)
Lopes AA, Leary PW. Cardiol Young 2009;19(E-Suppl.1):8-12
Shunt measurement
FICK PRINCIPLE
Wilkinson JL. Heart 2001;85:113
VO2
• Direct measurement is preferable, but not
practical in most institutions.
• Indirect prediction (tables, nomograms,
regression models) are unreliable.
• If assumption is used then more than one value
should be obtained – LaFarge, Lindhal, Lundell
etc.
• If difficulty with flow calculations use PVR/SVR
ratios ?
Lopes AA, Leary PW. Cardiol Young 2009;19(E-Suppl.1):8-12
Predicted VO2 calculated from regression equations
published by Lindhal, Wessel et al, Lundel et al.
Laitenen PO et al. Heart 1998;80:601
• LINDAHL (sedated, spontaneous breathing)
< 10 kg
> 10 kg
VO2 = (ml/min) = 6.8 x wt (kg) + 8
VO2 = (ml/min) = 4.0 x wt (kg) + 35.8
• WESSEL et al (sedated, spontaneous breathing)
VO2 = 144.8 x BSA (m2) + 5.6
• LUNDELL et al (sedated, spontaneous breathing)
< 3 years VO2 = 0.4 x wt (kg) + 1.91 x ht (cm) + 0.17 x H/R (beats/min) –
91.0
BOYS > 3 years = VO2 (ml/min) = 157.9 x BSA (m2) + 0.79x H/R
(beats/min) – 61.8
GIRLS > 3 years = VO2 (ml/min) = 159.0 x BSA (m2) + 0.77 x H/R
(beats/min) – 61.6
LaFarge & Mietten
Higher levels in younger children > lower PVR
Cardiovascular Research 1970;4:23-30
Patient
Cath date
(day/mo/yr)
Give 1 for Age<3
Sex: give 0 for
yr
1 minus D
female
Age (yr)
Weight
(kg)
1 minus F
Give 0 for
W<10
A.N.P.
21/11/2007
3,1
0
1
1
0
14,5
1
Saturation E-mail
pO2 address
Saturation
pO2excel based
Sat programme
pO2
Saturation Saturation
for access to
Hb(g/dL)
Pulm venous Pulm venous Pulm artery Pulm artery
Aorta
Aorta
Sup v cava Inf v cava
11,8
0,96
75
0,65
42,3
0,88
64,2
0,66
0,7
Venous-art O2
Arterio-venous O2
Mean pressure
Mean pressure
Mean pressure
Mean
difference
difference
(mmHg)
(mmHg)
(mmHg)
press(mmHg)
Pulmonary
Systemic
Pulm artery
Left atrium
Aorta
Right atrium
5,07298
3,42468
63
12
90
10
aablopes@usp.br
LaFarge & Miettinen
VO2 (ml/min)
105,976506
Lindal
LaFarge & Miettinen
VO2 (ml/min)/m2
Lindal
Bergstra
VO2 (ml/min)
170,4601897
Lundell
Bergstra
VO2 (ml/min)/m2
100,7149853
Lundell
Wessel
161,9971837
Wessel
VO2 (ml/min)
VO2 (ml/min)/m2
VO2 (ml/min)
VO2 (ml/min)/m2
VO2 (ml/min)
VO2 (ml/min)/m2
93,8
150,8746268
131,1677325
210,9795595
95,6233544
153,8074404
RESULTS
Qpi
Qpi
Qpi
Qpi
Qpi
3,360159 3,193334 2,974083 4,158888 3,031895
PVRi
15,17785
PVRi
15,97077
PVRi
17,14814
PVRi
12,26289
PVRi
16,82116
Qsi
Qsi
Qsi
Qsi
Qsi
4,9774049 4,7302867 4,4055102 6,1605627 4,491148
SVRi
16,07263
SVRi
16,91229
SVRi
18,15908
SVRi
12,98583
SVRi
17,81282
Qp/Qs
Qp/Qs
Qp/Qs
Qp/Qs
Qp/Qs
0,675082 0,675082 0,675082 0,675082 0,675082
PVR/SVR
0,944329
PVR/SVR
0,944329
PVR/SVR
0,944329
PVR/SVR
0,944329
PVR/SVR
0,944329
Computer-based matrix for rapid calculation of pulmonary haemodynamics in CHD
Lopes AA et al. Annals of Thoracic Medicine 2009;4:124
*
*
Failure to calculate dissolved O2 will result in an
overestimated PBF and lower PVR than is the case.
Wilkinson JL. Heart 2001;85:113
*
*
Some patients may achieve a substantial increase in
PBF associated with a large drop in PVR despite little
change in PAP.
Wilkinson JL. Heart 2001;85:113
Assumed VO2 – mostly adequate ?
Wilkinson JL. Heart 2001;85:113
• Young children 2-5 yrs
150 – 200ml/min/m2
• Infants younger than 3 months
130mls/min/m2
• Older infants
170mls/min/m2
• Children 1-2 years
200mls/min/m2
• Children 2-3 years
180mls/min/m2
• Adolescents
150ml/min/m2
• Adult women
100mls/min/m2
Males have a higher VO2 by 10-20% than females
A tachycardia above 150 beats/min associated with a 10% increase
compared with heart rates 120/min or lower
Ventilation
• Mechanically ventilated patients and degree
of anaesthetic depth and neuro-muscular
blockade – can decrease VO2 by 20-30%
(Rutledge et al. Am H J 2010;160:109)
Vasoreactivity test & operability ?
• Precise selection of patients is not possible.
• Operability is the likelihood of a favourable
vs unfavourable outcome using clinical, echo
and sometimes haemodynamic information.
• Best outcome PVRi < 6 WUm2 & PVR/SVR
ratio < 0.3.
• Vasodilator challenge if PVR 6-9 WU,
PVR/SVR ratio 0.3 -0.5?
Lopes AA, Leary PW. Cardiol Young 2009;19(E-Suppl.1):8-12
Vasodilator test
• 80-100% O2 x 10 min (Wilkinson JL. Heart 2001;85:113)
• OTHER PROTOCOLS WITH NO (expensive, not
always available):
Maximal stimulation ≥ 90% O2 + 80ppm NO
Less than maximal adequate:
20 ppm NO + any amount of O2
Intermediate protocols:
21-30% O2 + 80ppm NO or
100% O2 + 40 ppm NO
Lopes AA, Leary PW. Cardiol Young 2009;19(E-Suppl.1):8-12
Magnitude of response
• ≥ 20% decrease in PVRi (positive response, does
not imply operability !)*
• ≥ 20% decrease in PVR/SVR ratio*
• PVR < 6 WUi*
• PVR/SVR ratio < 0.3*
• Some patients with PVR ≥ 8-9 WUi and resistance
ratio ≥ 0.5 may be considered especially if large PBF,
but have high operative risk.
• NB - Response to pulmonary vasodilators suggests that
vasculopathy is not advanced but does not predict
favourable outcome. (Lopes A. Annals Thorac Med 2014;9:S21)
Lopes AA, Leary PW. Cardiol Young 2009;19(E-Suppl.1):8-12
Transpulmonary gradient
Index of PVR
• If elevated indicates increased PVR or
anatomic obstruction (e.g. pulmonary vein
obstruction).
• Increases following vasoconstriction of the
pulmonary arteries or veins or both.
Transpulmonary Gradient < 12mmHg
Independent of Flow
Gorlitzer et al. Transplant International 2005;18: 390
MPAP can be in excess of 40 mmHg with PVR remaining within an acceptable range,
therefore PAP alone provides an incomplete picture.
TPG vs PVR
mPAP vs PVR
Bell A et al. JACC 2009;3(11):1285
Effect of Viscosity on PVR !
TA1B (AM)
Post Glenn, pre-op Fontan
mPAP = 9 mmHg (<15)
TPG = PAm-LAm = 9-5mmHg =
4mmHg (< 8)
PBF 1L/min/m2
PVR = 9 Wood Units (<2.5)
Hct = 74 %
Hb 23g/dL
Relative Viscosity pre-op = 2 with Hct at 70% and PVR 9 WU pre-op
and 9/2 = 4.5 WU post op
Viscosity
• Calculations of PVR should consider effects of
blood viscosity.
• Resistance to flow through a tube is a function
of tube geometry (length & radius) x viscosity !!!
• To assess the geometric factor, resistance is
divided by viscosity to derive “hindrance”.
• For constant hindrance, halving the viscosity
halves the resistance, and doubling the viscosity
doubles the resistance.
• Hence in patients with polycythemia and Ht 70%
the viscosity is almost doubled !!
Hoffman J. Cardiac cath and angio
VISCOSITY !
Ht 74% wth hindrance of 2
Hoffman J. Cardiac cath and angio
Effect of Viscosity on Rp
Hoffman J. Cardiac cath and angio
Effect of Viscosity on PVR
TA1B (AM)
Post Glenn, pre-op Fontan
mPAP = 9 mmHg (<15)
TPG = PAm-LAm = 9-5mmHg =
4mmHg (< 8)
PBF 1L/min/m2
PVR = 9 Wood Units (<2.5)
Hct = 74 %
Hb 23g/dL
Relative Viscosity pre-op = 2 with Hct at 70% and PVR 9 WU pre-op
and 9/2 = 4.5 WU post op
Clear case of irreversible PHT ?
CM, 2yrs 8 mo, 9kg, LARGE PDA
Mild clubbing, cyanosis in RA
Conscious sedation – ivi Ketamine
Room air:
PCWP 7mmHg
87/47/65
PVR = 32 WU
TPG = 58mmHg
Qp/Qs
0.39:1
70% oxygen:
Rp/Rs
PCWP 1.7:1
6mmHg
90/59/76
87/47/65
PCWP 6mmHg
79/46/64
PVR = 15 WU
TPG = 58mmHg
62%
83%
60%
89/0/8
85/0/8
72%
99%
CM - echo
CM - ECG
No Q wave in V6
CM - angiography
Inoperable
Pulmonary Vasodilators ?
Balloon Occlusion can help with
decision making
PDA : Pre-balloon occlusion –balanced pressures
Balloon occlusion Operable
Saxena A. PHT in CHD.
PVRI 2009;2:101
Decisions based on calculations !
Balanced pressures in room air
115/52/83, 78%
KN, 6yrs, male:
From another Province
Palpitations
Pink, no clubbing
ECHO VSD 16 mm
Qp/Qs = 4.6:1
Rp/Rs = 0.27:1
PWP 11 mmHg
PVR 8 WU
mPAP = 83mmHg
TPG = 72mmHg
In 100% O2:
PWP 11 mmHg
PVR 2.8 WU
mPAP 58mmHg
114/78/97, 87%
Prominent PA segment, plethora, pruning
RVH
Large LA on venous return
Large VSD
Sudden tapering of peripheral
PA vasculature
No Q waves in V1
Q waves in V6
Treatment
Surgical Repair of VSD
• Stopped anti-failure medications 4 mo after
surgery.
• ECHO showed mild TR, PIG 46 mmHg
(3.4m/s).
• Has returned to Province of origin.
• Asymptomatic.
• PULMONARY VASODILATOR ??
Timing of surgery
• Persistently increased PAP can become
progressive with endothelial dysfunction
resulting in vasoconstriction and remodelling of
the pulmonary vascular bed.
• Changes can reverse if defect is repaired early.
• If delayed beyond 2 years of age PVR may fall
but does not reach normal levels.
• There may be a point of “no return” where
progression continues despite correction.
Beware effects of Anaesthetic agents !
Effect of Anaesthetic agents at cath
• PROPOFOL: Continuous infusion 100-200 ug/kg/min
* decrease SVR
* increase SBF
* increase R > L shunting
* reduced Qp:Qs
* No change in PVR and PBF
• KETAMINE: Continuous infusion 50-75 ug/kg/min
* increase systemic BP
* No change in mPAP, SVR and PVR
Oklu E et al. J of Cardiothoracic and Vascular Anaesthesia 2003:17:686
KETOFOL
Pediatric Emergency Care 2012;28(12)
RG, T21, 3yrs, AVSD, small VSD
PDA 6 mm, ligated 1 yr before
* Mild Clubbing
* NPO2
* Propofol infusion
PCWP 2mmHg
PVR 18 WU
Qp/Qs 0.5:1
Rp/Rs 16:1
mPAP 54 mmHg
TPG 52mmHg
81/32/57
58%
40%
85/-15/5
100/-10/10
58%
47%
Propofol infusion
54%
80/48/62
BP varied between
100/60 & 90/55
July 2013
RG, T21, 3yrs
Post PDA ligation 1 yr before
* Ketofol induction
* Sevoflurane maintenance
* Intubated
* O2 30%
61%
PCWP 4 mmHg
PVR 10 WU
Qp/Qs 0.87:1
Rp/Rs 0.9:1
mPAP 44mmHg
TPG 40 mmHg
65/17/40
72%
75/0/10
66/0/10
84%
69%
October 2013
RG
RG
Pruning, Small left atrium
RG
Bidirectional
shunting across large
ASD primum
Inoperable, progressive PVD
Histology
• Not recommended routinely.
• Useful in selected cases.
• Interpretation depends on quality of tissue
and expertise of pathologist.
Heath Edwards. Circulation 1958;18:533
6 Grades of pathological changes in PA of pts with CHD & PHT
2
3
1
Reversible up to grade 3 - Changes do not exceed grade 3 in PHT secondary to
pulmonary venous HT e.g MS. Histological changes may be distributed unequally and
may be missed in a given specimen!
1
2
Grade 6
Fibrinoid necrosis is associated
with severe PVR > 8 WU = refractory
to O2, prostacyclin or NO
3
4
5
Rabinovitch, M.
J of Clin Invest 2008
118;2372
Progression of PVD and effect on RV function
Champion HC et al. Circulation 2009;120:992
PHT due to left heart Disease
Right Heart
Pre-Capillary
PAWP normal
High PVR > 3 WU
Left Heart
Post-Capillary
PAWP > 15 mmHg
Normal PVR
High LAp, High LVEDP
Pulmonary vein stenosis
12yrs old
Haemoptysis
PCWP = 40 mmHg
Winter tree appearance angiographically
Ideopathic Pulmonary HT
Vasoreactivity Testing
Guidelines for diagnosis & Rx of PHT, EHJ, 2009
Positive Vasodilator response
Barst Criteria, Circulation 1999
Rashid A, Ivy D. Arch Dis Child 2005
Algorithm of Treatment
Ideopathic Pulmonary HT
Rashid A, Ivy D. Arch Dis Child 2005
Other less invasive diagnostic
modalities
Right heart catheterization and Doppler echocardiographic
measurements in 152 pts
D’Alto M. Int J of Cardio 2013;168:4058
Good correlation between right heart catheterization measurements
and echocardiographic estimates
Doppler ECHO indices for evaluation of PHT
Bossone E et al. J Am Soc Echocardiography 2013;26:1-14
PVR = (TRVmax/RVOTTVI) x 10 + 0.16
e.g. 2.78/11 x 10 + 0.16 = 2.68
The ratio TRV/TVI is normally ≤ 0.15
>2.8m/s
> 31 mmHg
PVR distinguishes high PAP due to high flow versus pulmonary vascular disease.
Not accurate with PVR > 8 Wood units. Normal PVR < 1.5 WU. Significant PH > 3 WU.
Echo Guidelines. Rudski LG et al. J Am Echo 2010;23:685
TDI & the RV
RV S’ or systolic excursion velocity has had population validation studies for the RV
S’ < 10 cm/s should raise suspicion for abnormal RV function especially in the younger patient
S’ > 10 cm/s
E/E’ ratio ≥ 4 has high S & S for predicting RA pressure ≥ 10 mmHg
Echo Guidelines. Rudski LG et al. J Am Echo 2010;23:685
Tissue doppler S’ lateral TVa
< 7.62cm/s = PVRCATH
> 6 WU/m2
TRV >3.96m/s
= PVRCATH > 6WU/m2
TRV/TVIRVOT >0.149
= PVRCATH > 6WU/m2
ECHO Doppler
Roushdy et al. J Saudi Heart Assoc 2012;24:233
MRI
the future ?
Op/Qs > 2.5:1
have a PVR ≤3.5WU
Bell A et al. JACC 2009;3(11):1285
(Lopes A. Annals Thorac Med 2014;9:S21)
History
Examination
Chest X ray
Transthoracic echocardiography
Catheterization
END