21/04/2018 Disclaimers Unrestricted educational grants from Actelion, GSK, Pfizer PAH related to congenital Consultant/speaker for Actelion, Pfizer heart disease in the adult RBH: unrestricted research grants from Actelion Kostas Dimopoulos MD MSc PhD FESC Adult Congenital Heart Centre & Centre for Pulmonary Hypertension Royal Brompton Hospital & Imperial College London London, UK PAH associated Eisenmenger PAH-CHD: the most common type or PAH with L-R syndrome shunt Bidirectional or RL Shunt L-R shunt R-L Endothelial dysfunction Shear stress & stretch Vascular Remodeling Histology I II III IV-V PVR PVR Lanigan MJ, Chaney MA, Tissot C, Beghetti M, Dimopoulos K. J Cardiothorac Vasc Anesth. 2013
21/04/2018 Scoliosis Cholelithiasis Clinical classification of PAH-CHD ↑ ↑ Pregnancy risk Gout Hepatic dysfunction Four different classes of PAH-CHD …plus a few more! ↑ ↑ Perioperative risk Hyperviscosity Renal failure Thrombosis Organ failure 1. Eisenmenger TIA/CVA Hyponatremia 2. L-R shunt Disability Bleeding Heart failure Syncope 3. Small defect Exercise intolerance Arrhythmias Sudden death ↓ QoL 4. Repaired + Endocarditis 1. Segmental PH 2. Fontan cooking cooking Kempny A et al. Eur Heart J 2011 Kempny A et al. Eur Heart J 2011;eurheartj.ehr461
21/04/2018 The haematologic effect of cyanosis General management principles Prevalence of iron deficiency and relation to saturations o Avoid dehydration, extreme isometric exercise o Avoid high altitude (cyanosis) o Air travel is safe in cyanotic pts: mobilise Broberg et al Heart 2006 o Special anaesthetic management o Avoid pregnancy: Contraception o Good dental/skin hygiene o Endocarditis/ cerebral abscess Oxygen saturation (%) o Treat iron deficiency, especially when Hb less than expected Prevalence of iron deficiency: 20-37% of patients with cyanotic CHD o Remain active within abilities, avoid strenuous isometric exercise Easily overlooked as standard laboratory methods (Hb, MCV) do not apply Diller, Dimopoulos et al. EHJ 2010 Why do cyanotic patients need a higher Erythrocytosis: higher blood viscosity but also higher hemoglobin exercise capacity Eisenmenger syndrome Erythrocytosis maintains adequate oxygen delivery to peripheral tissues Pulmonary blood flow Exercise capacity Secondary erythrocytosis Blood viscosity Diller et al, CITY 2010 Broberg et al. JACC 2006
21/04/2018 Iron supplementation in cyanotic ACHD: Anticoagulation? Exercise capacity and QoL No evidence for or against Increase risk of bleeding but also thrombosis Anticoagulate if: Previous confirmed embolic events 1. AF 2. Significant congestive heart failure 3. In situ PA thrombosis 4. Aspirin: No evidence Tay E, et al. IJC 2010 CXRs Over 10 years Haemodynamic collapse Transplantation? Stenting? Operation?
21/04/2018 Timing of death Cause of death Mortality risk of pregnancy in PAH related to CHD partum Pre- Week 12 Circulatory collapse Week 23 Severe RV failure iPAH Week 28 Severe RV failure p=0.047 CHD-PAH 12 h post Severe RV failure Maternal mortality risk oPH 1 day post Acute RV failure, intraperitoneal bleeding 60 56 30% 1 day post PE, RV failure Post-partum 2 days post Cardiac arrest Baby growth retardation 50 3 days post PE risk 80%: premature 40 5 days post Endocarditis, PE, RV failure 36 Risk of spontaneous 33 6 days post PE, RV failure 30 28 abortions % 30 7 days post Severe RV failure 7 days post Severe RV failure, PH crisis 17 20 14 days post Severe RV failure Also interruption of 21 days post PH crisis, RV failure, heavy vaginal bleeding 10 pregnancy carries 21 days post PE, RV failure significant risks 0 24 days post Severe RV failure 1997-2007 1978-1996 90 days post Circulatory collapse Bedard, Dimopoulos, Gatzoulis, EHJ 2009 Bedard, Dimopoulos, Gatzoulis, EHJ 2009 Arrhythmia in PAH-CHD Neonatal team Midwives Fetal medicine Nurse specialist O bstetrician Cardiology Cardiac theatre ward Anaesthetist Transplan C ardiologist Imaging tation & Cardiac & Obs VAD PHT team Haematology Arrhythmia, used as a time-varying covariate in the Cox model, was a strong predictor of death ITU & HDU staff HR 3.41, 95%CI: 2.10-5.53, p<0.0001 +Psychology Drakopoulou M et al. Under rev, Heart
21/04/2018 The remarkable right ventricle of Eisenmenger However, not all CHD-PAH have preserved syndrome RV function Eisenmenger iPAH Pretricuspid defects Complex defect The true survival of Eisenmenger Even within same anatomy: 2 cases of patients Eisenmenger PDA
21/04/2018 Echocardiographic Composite score Example of composite score Systole/Diastole duration Composite score • TAPSE<15mm • Systole/diastole time on TR ≥1.5 • RA area ≥25cm 2 • RA area/LA area ratio ≥1.5 S S D S D S RA area TAPSE RA/LA area Composite score • TAPSE<15mm • Systole/diastole time on TR ≥1.5 • RA area ≥25cm 2 • RA area/LA area ratio ≥1.5 6MWD, Albumin and BNP in Eisenmenger syndrome 1098 patients (median age 34∙4years, range 16∙1-84∙4years, 65∙1% female, 31∙9% with Down syndrome)
21/04/2018 The MUSES collaboration The MUSES collaboration Parameter Unit HR 95% CI P-value Age 10years 1·35 1·14 - 1·61 <0·001 Pre-tricuspid shunt - 1·97 1·12 - 3·46 0·019 Oxygen saturation at rest 10% 0·61 0·46 - 0·82 <0·001 Six minute walking distance 100m 0·67 0·54 - 0·82 <0·001 Presence of pericardial effusion - 2·35 1·33 - 4·13 0·003 Data from Kempny et al, Kempny et al, Circulation 2017 Circulation 2017 BREATHE-5: Reduced PVR and increased Long-term effect of PAH-advanced therapies 6-MWD 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 TE = -472 dyn·s·cm -5 , p = 0.038 TE = 53.1 m, p = 0.008 300 60 50 Change from baseline 200 Change from baseline PVR (dyn·s·cm -5 ) 40 100 6-MWD (m) 30 20 0 10 -100 0 -200 -10 -20 -300 -30 -400 -40 Placebo Bosentan Placebo Bosentan ( n = 17) ( n = 36) ( n = 17) ( n = 37) Galiè N, et al. Circulation 2006; 114:48-54. Diller GP, et al. Int J Cardiol 2012.
21/04/2018 PAH advanced therapies are associated with an MAESTRO study: macitentan in ES improved outcome in Eisenmenger patients A retrospective, single-centre study in 229 patients with ES 45 40 Cumulative mortality (%) No advanced therapies 35 30 p=0.015 25 20 HR 0.16, 95% CI: 0.04-0.71 15 10 5 Advanced therapies 0 • The primary endpoint evaluating change in 6MWD was not met. • NT-proBNP improved 0 1 2 3 4 5 6 7 • PVRi in the haemodynamic substudy favoured macitentan. time (years) • Macitentan was well tolerated in this patient population. Dimopoulos K, Inuzuka R, et al. Circulation 2010; 121:20-5. Case of PAH-CHD 27 year old lady What about other types of PAH-CHD? Born in 1990 in Asia Cardiac Diagnoses: Perimembranous VSD, PFO Presented at RBH at the age of 12 years
21/04/2018 Age 12 years VSD closure (13 years) VSD, PFO 14mm Amplatzer perimembranous VSD occluder AIR Qp/Qs = 2 QPi 6 L/min/m 2 The RV pressure post-deployment mPAP 44 mmHg 48/8 mmHg PVRi 6.5 WU x m 2 ★ ★ NO Air NO Qp/Qs = 3 Qpi 8 L/min/m 2 mPAP 44 mmHg PVRi dropped from 6.5 to 4.8 WU x m 2 K. Dimopoulos, S.J. Wort, M.A. Gatzoulis, European Heart Journal (2014) 35, 691–700 Admission at 23 weeks of pregnancy Cardiac catheterization (November 2016) (15 years) • Haemoptysis related to an upper respiratory infection • Increasing SOB Qp/Qs = 1 • Presyncope on effort Qp 3.2 L/min/m2 • AICU for advanced monitoring PVRi 13.4 WU x m2 • IV epoprostenol* and escalation of therapy by 1- 2005 2ng/kg/min according to tolerance Air NO ★ ★ ★ 2002 PVRi increased from ★ • Required respiratory support with CPAP and high flow O 2 ★ 6.5 (12y) to 13.4 (15y) WU x m2 Air NO K. Dimopoulos, S.J. Wort, M.A. Gatzoulis, European Heart Journal (2014) 35, 691–700
21/04/2018 Cardiac catheter 3 months post partum DO NOT close defects in established pulmonary vascular disease ★ Qp/Qs 0.67, PVR 16 WU, PVRi 26 2005 Repaired defects Air NO ★ ★ ★ 2002 ★ ★ TRIPLE THERAPY Air NO CONTRACEPTION TRANSPLANTATION K. Dimopoulos, S.J. Wort, M.A. Gatzoulis, European Heart Journal (2014) 35, 691–700 Other types of PAH-CHD Example of segmental PH Complex pulmonary atresia Segmental PH: ToF Complex Complex pulmonary atresia Pulmonary Atresia Large PDA to upper LPA Small MAPCA to mid L lung MAPCA to R lung PH in left upper lung/R lung? How do you calculate PVR? PH with a systemic RV: PAH therapies? Mustard TGA Accepted JAHA 2018
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