PAH related to congenital heart disease:...

transcript

PAH related to congenital heart disease: PAH-CHD

Kostas Dimopoulos

Royal Brompton Hospital

Imperial College London

London, UK

PAH-CHD: same prevalence as

iPAHUK National Audit of Pulmonary Hypertension 2011

... and many more

unidentified or lost to

follow-up

Large ventricular septal defect

Infancy: Lungs flooded

PVR = TPG

PBF>>CO

(Qp/Qs>>1)

TPG increases

PBF increases

PVR normal/mildly increased

PBF<CO

(Qp/Qs<1)

TPG increases

PBF decreases

PVR severely raised

Infancy/early adulthood:

Eisenmenger syndrome

Shear stress & stretch Vascular Remodeling

Bidirectional or RL

PAH associated

with L-R

Eisenmenger

syndrome

Endothelial dysfunction

IV-VII III

Histology

PVR PVR

Lanigan MJ, Chaney MA, Tissot C, Beghetti M, Dimopoulos K. J Cardiothorac Vasc Anesth. 2013

Interactive Questions

In which patients can you diagnose PH on

echo with confidence?

– 1 Only Eisenmenger patients with a post

tricuspid shunt (VSD, PDA)

– 2 All PAH-CHD patients

– 3 Any patient who has a good TR trace

In which patients can you diagnose PH on

echo with confidence?

– 1 Only Eisenmenger patients with a post

tricuspid shunt (VSD, PDA)

– 2 All PAH-CHD patients

– 3 Any patient who has a good TR trace

No cath is required for the diagnosis of Eisenmenger

syndrome in post-tricuspid defects

Large VSD

Low velocity bidirectional shunt

=RV pressure ≈ LV pressure

=Near-systemic PA pressures

+Desaturation at rest or min efforts

=Eisenmenger syndrome

Unlike

IN ALL OTHER PATIENTS, THE

DIAGNOSIS OF PH/PAH REQUIRES

CARDIAC CATHETERISATION

Baim DS and Grossman W. Cardiac Catheterization, Angiography, and Intervention.

Catheterisation essential for pretricuspid

Eisenmenger and non Eisenmenger pts

Ao - RA

PVR =PA - LA

Systemic vascular resistance

Pulmonary vascular resistance

http://www.med.umn.edu/intcardio/curriculum/modules/Hemodynamic/Hemodynamic_files/Hemodynamic.ppt

L-R shuntNo PVD

L-R shuntMild PVD

R-L shuntSevere PVD

Qp↑↑ Qp↑ Qp ↓

PAP↑↑ PAP↑↑ PAP↑↑↑

PVR=N PVR=↑ PVR=↑↑↑

Do not use thermodilution

PAPresssure not sufficient to define pulmonary vascular disease:

Need PVResistance

How many types of PAH-CHD are there

according to the ESC PH Guidelines?

– 1 One

– 2 Two

– 3 Three

– 4 Four

– 5 Five

How many types of PAH-CHD are there

according to the ESC PH Guidelines?

– 1 One

– 2 Two

– 3 Three

– 4 Four

– 5 Five

Clinical classification of PAH-CHDFour different classes of PAH-CHD

A. Eisenmenger’s syndrome (ES): shunt reversal

L-R-shunts due to large defects leading to a severe increase in PVR and resulting in a

reversed R-L or bidirectional shunt, resulting in cyanosis, high haemoglobin and multiple

organ involvement.

B. PAH associated with relevant L-R shunt (systemic-to-pulmonary)

L-R shunt through moderate to large defects, with mild to moderate increase in PVR, with

no cyanosis.

C. PAH with clinically not relevant L-R shunt

L-R shunt through small defects (usually VSD <1 cm or ASD <2 cm) with a clinical picture

very similar to IPAH.

D. PAH after corrective cardiac surgery

Corrected (closed) shunt, but PAH still present immediately after surgery or recurred

months or years after surgery, in the absence of significant post-operative residual shunt.

Adapted from Galiè N, et al. Eur Heart J 2009; 30:2493-537.

Of these 3 types of PAH-CHD, which could be

amenable to repair of the defect?

– 1 Groups B+C

– 2 Groups A+C

– 3 Groups A+B

– 4 Group B

– 5 All groups

A. Eisenmenger’s syndrome (ES):

shunt reversal

B. B. PAH associated with relevant L-

R shunt (systemic-to-pulmonary)

C. C. PAH with clinically not relevant

L-R shunt

Of these 3 types of PAH-CHD, which could be

amenable to repair of the defect?

– 1 Groups B+C

– 2 Groups A+C

– 3 Groups A+B

– 4 Group B

– 5 All groups

A. Eisenmenger’s syndrome (ES):

shunt reversal

B. B. PAH associated with relevant L-

R shunt (systemic-to-pulmonary)

C. C. PAH with clinically not relevant

L-R shunt

“Treat and repair”

IN 2014: THERE IS STILL NO EVIDENCE FOR TREATING WITH PAH THERAPIES

AND REPAIRING PREVIOUSLY INOPERABLE DEFECTS.

NEVER CLOSE DEFECTS IN

EISENMENGER PATIENTS!!!!

Or any patient with established

pulmonary vascular disease

The remarkable right ventricle of

Eisenmenger iPAH

However, not all CHD-PAH have

preserved RV function

Pretricuspid defects Complex defect

A. Eisenmenger’s syndrome (ES): shunt reversal

L-R-shunts due to large defects leading to a severe increase in PVR and resulting in a

reversed R-L or bidirectional shunt, resulting in cyanosis, high haemoglobin and multiple

organ involvement.

B. PAH associated with relevant L-R shunt (systemic-to-pulmonary)

L-R shunt through moderate to large defects, with mild to moderate increase in PVR, with

no cyanosis.

L-R shunt through small defects (usually VSD <1 cm or ASD <2 cm) with a clinical picture

very similar to IPAH.

Corrected (closed) shunt, but PAH still present immediately after surgery or recurred

months or years after surgery, in the absence of significant post-operative residual shunt.

Repaired defects

Why not to close defects in established pulmonary

vascular disease

The extreme end of PAH-CHD

Victor Eisenmenger, 1897

… The patient was a powerfully built man of 32 who gave

a history of cyanosis and moderate breathlessness since

infancy. He managed well until January 1894 when

dyspnoea increase and oedema set in. Seven moths later he

was admitted to the hospital in a state of heart failure.

He improved with rest and digitalis, but collapsed and died

suddenly on November 13 following a large haemoptysis”.

Paul Wood, 1958

Scoliosis

↑ ↑ Perioperative risk

Exercise intolerance Arrhythmias

Thrombosis

Heart failureBleeding

Organ failure

Hyperviscosity

↑ ↑ Pregnancy risk

Disability

↓ QoL Sudden death

Hepatic dysfunction

Renal failure

HyponatremiaTIA/CVA

Syncope

Cholelithiasis

Endocarditis

Dimopoulos et al. Circulation 2006

Dimopoulos. In Crawford et al. Cardiology, 2009

Exercise capacity in Eisenmenger

patients

Kempny A et al. Eur Heart J 2011;eurheartj.ehr461

cooking

Perception of functional capacity in ES

patients

Early onset of symptoms

Chronic adaptation of everyday

activities to a lower intensity

Patients underestimate their exercise

limitation compared with objective

measures of exercise tolerance

Dimopoulos K, Giannakoulas et al. Curr Opin Cardiol 2008; 23:545-54.

Who is functional

class III? ATs

What is differential cyanosis?

– 1 Cyanosis at effort but not at rest

– 2 Cyanosis in severe efforts only

– 3 Cyanosis that occurs in women but not men

– 4 Cyanosis that affects the lower body only

What is differential cyanosis?

– 1 Cyanosis at effort but not at rest

– 2 Cyanosis in severe efforts only

– 3 Cyanosis that occurs in women but not men

– 4 Cyanosis that affects the lower body only

Differential cyanosis:Patent Ductus Arteriosus with severe PAH

• Shunt: Bidirectional/R-L

• PBF: Reduced

• CO: Normal/reduced

• Cyanosis: ++ differential

PVRPVR

Bidirectional/RL shunt

PAH associated

with L-R shunt

Eisenmenger

syndrome

IV-VII III

Easy Δ iPAH vs Eis PDA

Always look at toes and measures sats

What is secondary erythrocytosis?

– 1 A compensatory increase in red cell count

aimed at increasing oxygen delivery

– 2 A malignant, extreme rise on RCC,

inevitably leading to thromboembolic events

– 3 An increase in RCC resulting in cyanosis

and iron overload

What is secondary erythrocytosis?

– 1 A compensatory increase in red cell count

aimed at increasing oxygen delivery

– 2 A malignant, extreme rise on RCC,

inevitably leading to thromboembolic events

– 3 An increase in RCC resulting in cyanosis

and iron overload

Erythrocytosis versus polycythemia

Secondary erythrocytosis in

cyanotic ACHD:

Isolated increase in Red cell

Often associated with

thrombocytopenia

Compensatory: a physiologic

response to chronic

hypoxia=USEFUL

Erythrocytosis: higher blood viscosity but also

higher exercise capacity

Broberg et al. JACC 2006

Exercise capacity

Blood viscosity

Hyperviscosity symptoms

Headache

Dizziness/lightheadedness

Fatigue

Visual disturbances, Tinnitus

Irritability, slow mentation,

dissociation,lethargy

Paresthesias (lips/toes), myalgias

Most are also

common

symptoms of

iron deficiency

in the general

population

Think: Cerebral abscess

Causes of CVA in ACHD: iron

deficiency and venesections

Risk of CVA is increased in the presence of:

• hypertension,

• atrial fibrillation,

• history of phlebotomy and microcytosis

(p = 0.005).

Ammash, Warnes, JACC 1996

Watch out for

bubbles!!

Phlebotomy: the RBH approach

Never prophylactic

Only for patients with moderate-severe hyperviscosity

symptoms (interfering with activities) in the absence of:

Dehydration

Iron deficiency

Minimum required volume to relieve symptoms 250-500ml

blood drawn over 30-45min, wait 24h

Adequate volume replacement (750-1000ml of saline for

250-500ml blood)

Monitor BP/satO2 at 15min intervals for 1h

Iron supplementation in cyanotic ACHD:Exercise capacity and QoL

Tay, Giannakoulas, Dimopoulos et al. IJC 2010

Niwa et al, 1999

Broberg CS et al, JACC 2007

PA thrombosis:

common in Eisenmenger syndrome

Unlike

Anticoagulation?

No evidence for or against

Increase risk of bleeding but also thrombosis

Anticoagulate if:

1. Previous confirmed embolic events

3. Significant congestive heart failure

4. In situ PA thrombosis

Aspirin: No evidence

Unlike

Bleeding

Causes of bleeding

Thrombocytopenia

Primary fibrinolysis

Factor deficiencies (liver, consumption)

DIC, increased sensitivity to activated protein C,

suppression of the thrombomodulin-protein C-

protein S pathway etc

Spontaneous

Easy bruising

Hemoptysis

cause of death in 11-30% of Eisenmenger pts

Gingival bleeding

Epistaxis

Menorrhagia

Perioperative

Haemodynamic collapse

Mustard

Aortic coarctation

Valve disease

Tetralogy of Fallot

Complex

VSDFontan

Atrial septal defect

ccTGAEbstein anomaly

Eisenmenger physiology

Cyanotic ACHD:

renal dysfunction is commonNormal

Moderate-Severe

0 20 40 60 80 100

%Dimopoulos et al. Circulation 2008

A young woman with PAH-CHD come to your clinic saying

she is planning to start a family soon. She is overweight and

is taking sildenafil. You advise her:

1. 1 To lose some weight because obesity is a risk factor during

pregnancy

2. 2 To not become pregnant until she has started taking

bosentan to improve her hemodynamics

3. 3 To not become pregnant, pregnancy carries prohibitive

risks in PAH-CHD. She should be on contraceptions ASAP

4. 4 To stop taking sildenafil, it is not safe during pregnancy

A young woman with PAH-CHD come to your clinic saying

she is planning to start a family soon. She is overweight and

is taking sildenafil. You advise her:

1. 1 To lose some weight because obesity is a risk factor during

pregnancy

2. 2 To not become pregnant until she has started taking

bosentan to improve her hemodynamics

3. 3 To not become pregnant, pregnancy carries prohibitive

risks in PAH-CHD. She should be on contraceptions ASAP

4. 4 To stop taking sildenafil, it is not safe during pregnancy

Mortality risk of pregnancy in PAH related to CHD

Bedard, Dimopoulos, Gatzoulis, EHJ 2009

1997-2007 1978-1996

CHD-PAH

p=0.047

Maternal mortality risk

Baby growth retardation

risk 80%: premature

Risk of spontaneous

abortions

Also interruption of

pregnancy carries

significant risks

Timing of death Cause of death

Week 12 Circulatory collapse

Week 23 Severe RV failure

Week 28 Severe RV failure

12 h post Severe RV failure

1 day post Acute RV failure, intraperitoneal bleeding

1 day post PE, RV failure

2 days post Cardiac arrest

3 days post PE

5 days post Endocarditis, PE, RV failure

6 days post PE, RV failure

7 days post Severe RV failure

7 days post Severe RV failure, PH crisis

21 days post PH crisis, RV failure, heavy vaginal bleeding

21 days post PE, RV failure

90 days post Circulatory collapse

Bedard, Dimopoulos, Gatzoulis, EHJ 2009

Obstetrician

CardiologistAnaesthetist

Cardiac & Obs

Transplan

tation &

Neonatal team

Imaging

Midwives

Cardiology

PHT team

Cardiac theatre

specialist

Fetal medicine

ITU & HDU staffHaematology

+Psychology

A patient with Eisenmenger syndrome present with a

syncope, mild fever and night sweats. What do you

want to exclude immediately?

1. 1 Complete heart block

2. 2 Hyperkalemia secondary to renal dysfunction

3. 3 Acute myocardial infarction

4. 4 Cerebral abscess

5. 5 Massive pulmonary emboli

6. 6 Urinary tract infection

A patient with Eisenmenger syndrome present with a

syncope, mild fever and night sweats. What do you

want to exclude immediately?

1. 1 Complete heart block

2. 2 Hyperkalemia secondary to renal dysfunction

3. 3 Acute myocardial infarction

4. 4 Cerebral abscess

5. 5 Massive pulmonary emboli

6. 6 Urinary tract infection

Cerebral Abscess

Clots are not the only possible emboli

Endocarditis Prophylaxis

Pseudohypoglycemia

Low glucose concentration:

- In venous blood, in vitro consumption of glucose by high levels of cells

in the blood after the sample is drawn and before it is processed:

- Process sample immediately or

- Cool sample or

- Use inhibitors of anaerobic glycolysis

- finger-stick blood pseudohypoglycemia: impaired digital

microcirculation, local increase in glucose consumption

Theofilogiannakos EK, Giannakoulas G, et al. Ann Intern Med. 2010;152(6):407-8

Ybarra J, et al. Endocr J. 2003;50:481-2.

BREATHE-5: Reduced PVR and

increased 6-MWD

Placebo

(n = 17)

Bosentan

(n = 36)

Placebo

(n = 17)

Bosentan

(n = 37)

Galiè N, et al. Circulation 2006; 114:48-54.

TE = -472 dyn·s·cm-5, p = 0.038 TE = 53.1 m, p = 0.008

Long-term effect of PAH-advanced therapies

in Eisenmenger patients*The graph depicts average change compared to baseline, with 10%, 25%, 75% and 90%

percentiles derived from bootstrap analysis. P-values refer to repeated measure ANOVA

results

Diller GP, et al. Int J Cardiol 2012.

PAH advanced therapies are associated with

an improved outcome in Eisenmenger patients

A retrospective, single-centre study in 229 patients with ES

Dimopoulos, Inuzuka, Goletto, Giannakoulas et al. Circulation 2010; 121:20-5.

0 1 2 3 4 5 6 7

No advanced therapies

Advanced therapies

p=0.015

time (years)

HR 0.16, 95% CI: 0.04-0.71

PH & ACHD

Specialist

Centre

Transplantation

Paediatric

Cardiac

Centre

Transition

High risk

anaestetics/AICU

High risk

obstetrics

Genetics

Heart failure

services

Diagnostic

imaging

Exercise

physiology

Electrophysiology

Dentistry

Local ACHD

Centres

Palliative care

Rehabilitation

Designated National PH Centres

http://www.pulmonaryhypertensioncentres.co.uk/

Shared care centres

Southampton

General Hospital

John Radcliffe Hospital

https://catalogue.ic.nhs.uk/publications/clinical/heart/nati-pulm-hype-audi-2012/nati-pulm-hype-audi-2012-rep.pdf

Importantly, only the designated centres

are able to initiate treatment with a

disease-targeted medicine under this

policy. In some circumstances, explicit and

formalised shared-care agreements may

be made by the designated centres with

other specialist centres to prescribe disease-

targeted therapies. However, nonspecialist

clinicians and General Practitioners should

not be asked to routinely

prescribe these medicines since they are not

able to submit information to the national

database.

http://www.england.nhs.uk/wp-

content/uploads/2013/04/a11-ps-a.pdf

Changing

A. Eisenmenger syndrome (ES)

B. PAH associated with relevant L-R shunt

Treat with PAH therapies

DO NOT CLOSE DEFECT

DO NOT CLOSE RESIDUAL

DEFECTs

PAH therapies??

Selected cases may benefit from

defect closure: ACHD centre

Check national guidelines and licences .

Thank you!

PAH related to congenital heart disease:...

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