1 / 49

Grand Rounds March 2005

Grand Rounds March 2005. “I Forgot I was Breathless” Michael Hayes. Mrs HJ. 44 yo Married BMI 40 Smoker 20 pack years Presenting with progressive dyspnoea over 2 years. Background. Childhood brain tumour Hydrocephalus → shunt Epilepsy Controlled

Download Presentation

Grand Rounds March 2005

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Grand Rounds March 2005 “I Forgot I was Breathless” Michael Hayes

  2. Mrs HJ • 44 yo • Married • BMI 40 • Smoker 20 pack years • Presenting with progressive dyspnoea over 2 years

  3. Background • Childhood • brain tumour • Hydrocephalus → shunt • Epilepsy • Controlled • Chronic short term memory difficulties

  4. Background (cont.) • 1991 surgical revision of VP shunt • Post op DVT

  5. Background (cont.) • 2002 unprovoked DVT left leg • Warfarin commenced • Thrombophilia screen • Uncertain hx of sister DVT • Post phlebitic syndrome

  6. Background (cont.) • Dyspnoea mid 2003 (still on warfarin) • No chest pain, cough or haemoptysis • No orthopnoea or PND • Hx of snoring, witnessed apnoeas, fatigue

  7. Ix • CXR and ECG • CT chest 2001 and 2004 • ↓ volume L lung. LLL changes • V/Q scans • CTPA • Sleep study – OSA but intolerant of CPAP • Spiro normal 2003

  8. Further assessment 2004 • Profound hypoxia 91% on 2 litres at rest 76% after walking 20 metres • Examination – little to find • ECG

  9. PFT’s

  10. Diagnosis ?

  11. Echocardiogram • RV dilation and hypertrophy • PAP 50-55 mmHg • PFO with R to L shunting on standing and exercise • “orthodeoxia”

  12. Pulmonary Artery Hypertension • Cause in this woman ?

  13. Treatment • Long term oxygen therapy • Continued warfarin

  14. Progress • Worsening exercise tolerance • Retrosternal chest pains – nocturnal • odynophagia • Dry cough – post tussive vomiting • No benefit from PPI • Pertussis serology negative

  15. Admission • Gastroscope • Mild oesophagitis. Monilial plaques • Small sliding HH • Reassess PAH • Echo PAP now 75-80mmHg • 6 min walk 187 metres

  16. Admission • Telangiectases on hands • No other signs of connective tissue dx • ANA 1:640 • Anti-centromere antobodies • other ENA negative ? significance

  17. Management • Right heart catheter • Bosentan (endothelin receptor antagonist)

  18. Pulmonary Artery Hypertension Pulmonary artery hypertension is present when mean pulmonary artery pressure exceeds 25 mmHg at rest, or 30 mmHg with exercise.

  19. Types • Primary • Secondary

  20. Ohm’s law • Δ pressure = flow х resistance • Ppa – Ppv = Q х PVR • Ppa = (Q х PVR) + Ppv

  21. Secondary Causes • Hypoxic vasoconstriction • COPD, Hypoventilation disorders • Decreased area of pulm vascular bed • large artery obstruction – PE • small artery obstruction – PE, CT disease, vasculitis • Volume & pressure overload • ASD, VSD • LA hypertension – MS or MR, LV dysfunction • Pulmonary venoocclusive dx

  22. Other Causes • familial • Amphetamines • HIV • Anorectic drugs • HHV-8 • Portal hypertension

  23. Primary • Diagnosis of exclusion • PAH with no other secondary cause

  24. PAH begets PAH • Initial cellular/molecular mechanisms vary • Final common pathway • Endothelial dysfunction • Oxidative damage • Impaired vascular smooth muscle regulation • Muscularisation, intimal hypertrophy, intimal hyperplasia

  25. Clinical Features • Dyspnoea on exertion • Progressive • Fatigue / lethargy • Exertional chest pain • Presyncope or syncope • Signs of RVF

  26. Examination • Widening & fixed splitting of S2 • Increased intensity P2 • A right ventricular heave • Jugular venous distension • Prominent A and V wave venous pulsations • A right ventricular S3 • Murmurs of tricuspid regurgitation or pulmonic insufficiency • Peripheral edema • Hepatomegaly • Ascites

  27. Role of Echo • Echocardiography commonly provides the initial objective evidence for pulmonary artery hypertension

  28. Echo • Far more sensitive than the clinical examination • Himelman RB et al. Am J Med 1988 • 33 COPD • Cor pulmonale defined as PAH + RV hyper identified in 39% clinically (exam, ECG, CXR) • 75% by echo

  29. Echocardiography • Berger M et al. J Am Coll Cardiol 1985 • PAP > 35mmHg • 80% sensitivity • PAP > 50mmHg • 95% sensitivity • 97% correlate of measured pressure with R heart catheter Exercise echo increase sensitivity

  30. R Heart Catheter • Gold standard • Diagnosis and quantification • Indications • Echo doesn’t permit measurement of TR jet • Verify presence and severity of L to R shunts • ? When therapy is determined by precise measurement of PVR and response to vasodilators • Highly suspected and noninvasive is not definitive

  31. PFT’s • Most have ↓ DLCO • Normal does not exclude PAH • Often a mild restrictive deficit

  32. Often delayed diagnosis • Subtle clinical signs initially • PPAH - average 2.5 yrs from symptoms till diagnosis • SPAH - manifestations often masked by underlying aetiology

  33. Important ! • The status of the pulmonary vascular bed should be considered in any patient with dyspnoea in whom no compelling cause can be established.

  34. PPAH - terrible disease • Mean survival from diagnosis is 3 years for PPAH • Severe PAH or RVF tend to die in 1 year • Development of SPAH worsens prognosis in many of the causative conditions

  35. Treatment • SPAH • Treat underlying disease • Prior to irreversible damage • Specific interventional and medical therapies can correct PAH

  36. Treatment • O2 therapy • Anticoagulation • Ca2+ blockers • Prostacyclin • Endothelin receptor antagonists (Bosentan) • Phosphodiesterase inhibitors • Transplant

  37. Oxygen • Used in COPD • Good evidence for improved survival • Use extrapolated to other groups of patients with SPAH

  38. Anticoagulation • Some evidence of improved survival in PPAH if non-uniform blood flow on perfusion scan • Clearly indicated with chronic PE • Some investigators recommend in all cases of SPAH

  39. Ca2+ antagonists • Use in PPAH only • Need haemodynamic study to identify response to vasodilators • 25 – 30% of patients • Evidence for survival benefit in “reponders”

  40. Prostacyclin • Good evidence for improved survival in PPAH • Evidence for improved functional capacity in SPAH – limited use • Continuous infusion • Inhaled prostacyclin analogue • Oral analogue

  41. Bosentan • Endothelin receptor antagonist • Endothelin is potent vasoconstrictor and proliferative agent • Is over-expressed in lungs in PPAH • Increased plasma levels in PPAH, IPF, CT disease

  42. Proven efficacy of bosentan in PPAH • Clinical studies in PPAH show: • Improved hemodynamics, exercise capacityand WHO functional class 1,2 • Delay in time to clinical worsening 2 • Improvements in RV and LV function andpositive effects on cardiac remodeling 3 • Efficacy maintained over time with stableWHO functional class (1 yr) 2,4 • Improved Survival and QoL5,6 • 1 Channick et al. 2001 2 Rubin et al. 2002 3 Galié et al. 2003 4 Sitbon et al. 2003 5 Mc Laughlin et al. 2003 6 Keogh et al. 2004

  43. Improves survival • McLaughlin et al. Eur. Resp. Journal Feb 2005 • 3 year follow-up of 169 pts with PPAH • Pts enrolled in 2 studies of bosentan as first line therapy

  44. 100 90 Observed1 80 70 60 % of event-free patients 50 Predicted(NIH2) 40 30 20 Event Rate / year (exponential): 5.5% 10 0 0 6 12 18 24 30 36 months 169 167 163 153 113 23 16 Patients at risk 1Mc Laughlin et al. Am J Respir Crit Care Med 2003;167:441 2 D’Alonzo et al, Ann Intern Med 1991;115:343 Bosentan long-term outcome Kaplan-Meier survival estimates with 99% CIfor observed vs predicted survival

  45. Of initial cohort 78% and 55% were alive and on bosentan monotherapy at 1 and 2 years • Major adverse effect was transaminitis in up to 14%

  46. Summary • PAH is a difficult diagnosis to make. Suspect it! • Echocardiography is good investigation along with CXR, ECG, PFT’s • Now therapies with reasonable evidence of efficacy

More Related