Pulmonary hypertension on echo-

what next….?

Simon MacDonald BSc(Hons) BMBCh DPhil FRCP

Consultant Cardiologist in Adult Congenital Heart Disease

Definition of PAH

• Mean PA pressure ≥ 25mmHg

• Precapillary if PAWP ≤ 15mmHg

• Post capillary if PAWP≥ 15mmHg• Isolated post capillary PH (IpCH): DPG < 7mmHg and/or PVR ≤3• Combined post capillary PH (CpCH); DPG ≥ 7mmHg and/or PVR > 3 Woods

Units

ESC Guidelines 2016- Galie N et al, EHJ (2016) 37:67-119

PAH Definition

• Measurement variability• Caution

PAH Types

• Can involve multiple conditions

• Five groups

Simonneau G et al, JACC 2013; 62: D34-41

PAH Epidemiology

• 97 cases per million in UK

• Female: male 1.8:1

• Mean age at diagnosis between 50 and 65yrs of age

• Group 1: 15-5.9 cases per million

• Group 2: 60% pts with severe LVF, 70% HFpEF, all severe MR, 65% severe AS. Most common group

• Group 4: CTEPH 3.2 cases per million

PAH presentation

Symptoms:

• Exertional breathlessness

• Fatigue, weakness, angina, syncope

• Abdominal distension, ankle oedema if RV failure

• Haemoptysis

• Hoarseness, angina- compression symptoms laryngeal nerve, LMS

Signs:

• Parasternal heave, raised JVP loud P2, tricuspid PSM, PR murmur, hepatomegaly, ascites, oedema, mimimal wheeze/ crackle

PAH Ix Findings

• ECG: p pulmonale, right axis, RV hypertrophy, RV strain, RBBB, QTcprolongation, flutter/ fibrillation (25% after 5 years).

• CxR: central PA dilatation, RA and RV enlargement

• Echo: estimation of PAP

PAH and Echo

Galie N et al, EHJ 2016; 37: 67-119

PAH and echo

• Severe TR- caution

Galie N et al, EHJ 2016; 37: 67-119

PAH- other tests

• VQ scan• CTEPH• Higher sensitivity than CTPA (normal excludes CTEPH with sensitivity of 90-100%)

• Hi res CT• Vascular, cardiac, parenchymal abnormalities• PA >29mm, PA:Ao>1.)

• Cardiac MRI• Congenital heart disease, shunts, stroke volume, CO, fibrosis

• Blood tests and immunology• Biochem, haematology, LFTs, hepatitis serology, HIV, systemic sclerosis

• Abdominal ultrasound

PAH- right heart cath

• Low morbidity (1.1%) and mortality (0.055%)

• Expert centres, attention to detail

• Catheter reactivity (NO, iloprost, IV adenosine or epoprostenol)• Reduction mean PAP ≥ 10mmHg to reach mean PAP≤40mmHg with increased

or unchanged CO

• Can treat high doses of CCB

PAH

• Diagnostic algorithm

PAH- severity

• WHO functional class I-IV

• 6 minute walk tests• Borg score for breathlessness

• CPET

• Biochemistry

• Imaging- echo

PAH Risk assessment

Galie N et al, EHJ 2016; 37: 67-119

Therapy

• General• Pregnancy, birth control, surgery, infection control,

• Supportive Rx: anticoagulants, diuretics, digoxin, O2

• High dose CCBs if reactive, PAH drugs if not reactive

• Review response- escalate, combination therapy, transplant

• Avoid ACE-I, beta-blockers, ivabradine?

Pregnancy and PAH ACHD

• Still high risk

Bedard E et al, EHJ, 2009

Therapies

High dose calcium channel blockers• Nifedipine 120-240mg, diltaizem 240-720mg, amlodipine 20mg

Endothelin Receptor antagonists• ET-1 A and B receptors on pulmonary vascular smooth muscle

• Ambrisentan (Type A)

• Bosentan (Type A and B). Six RCTs• 10% get abnormal LFTs

• Macitentan (Type A and B)

Therapies

Phosphodiesterase type 5 inhibitors and guanylate cyclase inhibitors• Inhibition of cGMP degrading via PDE type 5 enzyme causes vasodilation

• Sildenafil-4 RCTs 20mg to 100mg tds• Side effects: headache, flushing, epistaxis

• Tadalafil 2.5 to 40mg od

• Riociguat-stimulator of soluble guanylate cyclase (cGC)

Prostacyclin analogues/ prostacyclin receptor agonists• Endothelial cell production of prostacyclin- vasodilator

• Epoprostenol- infusion (T1/2 3-5 mins)-risk reduction 70% mortality

• Treprostinil- s/c and IV

Treatment Pathway

• Group 1PAH

Additional PAH therapies

• Balloon atrial septostomy• Avoid if RAP >20mmHg, O2 sats <85% in air

• RV failure• Reduce RV afterload (prostacyclin)

• Increase CO with inotrope- dobutamine with BP maintained with vasopressors

• Be wary of intubation- risk of death

• ECMO

PAH therapies

• Group II• Treatment of left heart disease?

• Group III• PAH therapies do not work?• O2 therapy

• Group IV- CTEPH• Life long anticoagulation• Operation- pulmonary end-arterectomy• Non-operative- balloon dilatation

PAH associated with CHD

• Approximately 5-10% of adults with CHD will develop PAH

Collins NR et al, Cardiol Clin 1993; 11:675-87

Clinical classification of congenital, systemic-pulmonary shunts associated with PAH

• Eisenmenger syndrome• L-R shunt due to large defects leading to severe increase in PVR and reversed (R-L) or bidirectional shunt

• Pulmonary arterial hypertension associated with L-R shunts• Moderate to large defects, increase in PVR mild-moderate, L-R shunt is still largely present and no cyanosis at rest

REPAIRABLE

• Pulmonary arterial hypertension with small defects• Clinical picture very similar to idiopathic PAH• VSD<1cm, ASD< 2cm effective diameter

• Pulmonary arterial hypertension after corrective surgery• Congenital heart disease been repaired but PAH is either:

• Still present immediately after surgery or• Recurred several years after surgery

In absence of significant residual lesions

Simonneau G et al, JACC 2013; 62: D34-41

Eisenmenger syndrome• 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 dsypnoea increased and oedema set in. Seven months later he was admitted to 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

PAH-CHD ≠ stable disease

Diller GP et al, EHJ 2006;27: 1737-42

The impact of functional class on long-term survival

Dimopoulos K et al, Circulation 2010; 121:20-5

Mode of death in Patients with Eisenmenger Syndrome

• Right ventricular failure

• Sudden cardiac death

• Surgery

• CVA/ Abscess

• Haemoptysis

• Extracardiac surgery

• Transplantation

Somerville J IJC 1998

UK and Ireland national pulmonary hypertension centre management algorithm for ES

Gibbs S et al, Heart 2008; 94 (suppl):i1-i41

Prevalence of iron deficiency and relation to saturations

• Prevalence• 20-37% of patients with cyanotic CHD

• Easily overlooked as standard laboratory methods (Hb, MCV) do not apply

• Anaemia difficult to define as Hb rises with the fall in resting saturations

• Relates to higher incidence of stroke: VENESECTION NOT ADVISED

Diller GP et al, EHJ 2006;27: 1737-42

Iron repletion

Tay E et al IJC 2010

Cyanosis and need for higher haemoglobin• Higher Hb maintains adequate oxygen delivery to peripheral tissues

• Erythrocytosis causes higher blood viscosity but also higher exercise capacity

Broberg CS et al, JACC 2006; 48: 356-65

PA thrombus formation in Eisenmenger syndrome

Eisenmenger Syndrome- Bleeding

• Spontaneous, perioperative

• Common haemorrhagic events:• Easy bruising • Haemoptysis• Epistaxis• Gingival bleeding• Menorrhagia• Bleeding secondary to trauma/ surgery

• Causes• Thromboctyopenia, primary fibrinolysis, Factor deficiencies (liver/ consumption), DIC• Increased sensitivity to activated protein C, suppression of thrombomodulin-protein C-

protein S pathway etc

Haemoptysis: the cause of death in 11-30% of Eisenmenger patients

Transplantation

HLT superior to LT435HLT/605 LT Tx in CHD pts 1988-98 from international registry

• 1 year survival 81% and 70% respectively• 5 year survival approximately 50%

Increased perioperative risk- bleeding51 Eisenmenger pts with HLTSimilar long-term survival with non-Eisenmenger pts

• Selection criteria and timing?

Waddell TK et al, J Heart Lung Transplant 2002Stoica SC et al, Ann Thorac Surg 2001

PAH due to LV disease

PAH due to LV disease

PAH due to LV disease

PAH summary

• Definition- mean PAP ≥ 25mmHg

• Groups I-V

• Presentation, Signs and Investigations

• Assessment of severity

• Therapies- according to group:• General

• Ca channel blockers, ERAs, PDE-5 inhibitors, cGMP stimulators, prostacyclin

• Cardiac- Congenital heart disease and LV dysfunction