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Pulmonary Hypertension and Congestive Heart Failure

Pulmonary Hypertension and Congestive Heart Failure. Stephen L. Rennyson MD August 11, 2011. Pulmonary Hypertension. Mean Pulmonary Artery Pressure (mPAP) > 25 mmHg. WHO Classification of Pulmonary Hypertension. 1. Pulmonary Arterial Hypertension. 2. Left Heart Disease.

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Pulmonary Hypertension and Congestive Heart Failure

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  1. Pulmonary Hypertension andCongestive Heart Failure • Stephen L. Rennyson MD • August 11, 2011

  2. Pulmonary Hypertension • Mean Pulmonary Artery Pressure (mPAP) • > 25 mmHg

  3. WHO Classification of Pulmonary Hypertension 1. Pulmonary Arterial Hypertension 2. Left Heart Disease 3. Chronic Hypoxemia 5. Miscelaneous 4. Thromboembolic -Sarcoid, fibrosing mediastinitis

  4. Relationship of CHF and PH • Passive Congestion (Elevated PCWP) Increased LVEDP (PCWP) Pre - Capillary vs Post - Capillary PH

  5. Group 2 PH • Comprises 1/2 of all PH • Systolic and Diastolic Dysfunction • Leads to RV dysfunction • Difficult to treat -- Cardio-Renal Syndrome • Independently associated with worse outcomes

  6. Group 2 PH • Independent predictor of mortality RVSP RVSP Congestive Heart FailureVolume 17, Issue 4, pages 189-198, 21 JUL 2011 DOI: 10.1111/j.1751-7133.2011.00234.x

  7. Survival after Cardiac Transplantation • Elevated PAP and Low RV function Group 1 indicates normal pulmonary artery pressure/preserved right ventricular ejection fraction (n=73); group 2, normal pulmonary artery pressure/low right ventricular ejection fraction (n=68); group 3, high pulmonary artery pressure/preserved right ventricular ejection fraction (n=21); and group 4, high pulmonary artery pressure/low right ventricular ejection fraction (n=215). Voelkel N F et al. Circulation 2006;114:1883-1891

  8. Cardiac Catheterization

  9. Hemodynamic Assessment • Right Heart Catheterization • RA, RV, PAP, PCWP • Thermodilution and Fick • End Expiration -- Best approximate of atmospheric pressure

  10. Transpulmonary Gradient (TPG) • Change in pressure across the pulmonary circulation • mPA - PCWP • Normal TPG < 10 mmHg

  11. Pulmonary Vascular Resistance • Resistance to flow that must be overcome to push blood through the system • Ohms Law: • mPA - PCWP • Cardiac Output Normal Values of < = to 1.5 Wood Units

  12. PH due to CHF • Pre Capillary PH • mPA > 25 mmHg • PCWP < 15 mmHg • CO normal • Post Capillary PH • mPA > 25 mmHg • PCWP > 15 mmHg • CO normal or low

  13. Post Capillary PH out of proportion • Use of TPG and PVR • TPG > 10-12 mmHg • PVR > 1.5 wood units

  14. PH out of proportion Active or Reactive PH Elevated mPA beyond PCWP TPG> 10-12 Passive PH Elevated mPA solely attributed to PCWP TPG < 10-12 Tx Based on Traditional CHF management ?? Tx Based on Traditional CHF management

  15. Reactive PH Longstanding Advanced Heart Failure Chronic Venous hypertension Mediated by Endothelin • Pulmonary Vascular Remodeling • Elastic Fibers • Intimal Fibrosis • Medial Hypertrophy Changes -- Indistinguishable from PAH

  16. Pulmonary Remodeling Does not normalize with traditional CHF treatments “Fixed” Pulmonary Arteriopathy Ultimately RV Failure

  17. Reactive Changes • Vasodilator Challenge • Inhaled NO, IV epoprostenol, milrinone, nitroprusside, nitroglycerin, dobutamine . . . • ISHLT guidelines -- Vasodilator Challenge • mPA > 50 mmHg AND • TPG > 15 mmHG OR • PVR > 3 Wood Units

  18. Vasodilator Challenge VCU/MCV -- NO challenge Reactive Changes with Fixed PH: --Persistent PVR >=2.5 WU or --PVR < 2.5 WU secondary to SBP <85 mmHg

  19. Right Ventricular Failure RV Hypertrophy RV Dilation Flattening of Interventricular Septum -- D Shaped LV RA Enlargement Tricuspid Regurgitation

  20. Right Ventricular Evaluation • Transthoracic Echocardiography • Qualitative • Quantitative • Tricuspid Annular Peak Systolic Excursion (TAPSE) -- > M-mode • Tissue Doppler • First Pass (RVEF) • MRI

  21. TAPSE American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 1034-1041, (2006)

  22. TAPSE (< 1.8 cm) American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 1034-1041, (2006)

  23. TAPSE (< 1.8 cm) American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 1034-1041, (2006)

  24. TAPSE (< 1.8 cm) American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 1034-1041, (2006)

  25. Medical Management Flolan Sildenafil Prostacyclin Bosentan / Darusentan Moraes D L et al. Circulation 2000;102:1718-1723

  26. Role for pulmonary vasodilators? • Prostanoids -- FIRST Trial -- Flolan • Endothelial Receptor Antagonists REACH and ENABLE trials -- Bosentan • Phosphodiesterase Inhibitors -- Sildenafil

  27. FIRST Flolan International Randomized Survival Trial • 471 patients class III/IV • Improved Hemodynamics • Increased CI / Decreased PVR and PCWP • Exercise Tolerance and QOL • No Change • Increased Mortality • Contraindicated Am Heart J 1997;134:44-54

  28. REACH Research of Endothelin Antagonists in Chronic Heart Failure • 370 Patients • High dose Bosentan vs Placebo • Trial Stopped Early • Increase in early CHF exacerbations • Elevated Transaminase Levels

  29. ENABLE Endothelin Antagonist Bosentan for Lowering Cardiac Events in Heart Failure • 1600 Patients Bosentan (lower dose) vs Placebo • Increased CHF exacerbations

  30. Phosphodiesterase Inhibitors

  31. Sildenafil • No large scale clinical trials • Acute Hemodynamic Trials • Long Term Hemodynamics • Quality of Life Trials

  32. Acute Hemodynamic Changes • 11 patients • Right Heart Cath • Inhaled NO (80 ppm) • Sildenafil (50 mg) • NO/Sildenafil combination Lepore JJ, Maroo A, Bigatello LM, et al. Chest. 2005;127:1647-1653

  33. Duration of Effect NO Alone NO and Sildenafil Lepore JJ, Maroo A, Bigatello LM, et al. Chest. 2005;127:1647-1653

  34. Acute Changes Lepore JJ, Maroo A, Bigatello LM, et al. Chest. 2005;127:1647-1653

  35. Chronic Therapy • 34 patients, 12 week trial • Sildenafil vs Placebo (75 titrated to 150 mg/day) • Class II-IV NYHA CHF, (iCMO and NiCMO) • Hemodynamic and Qualitative measurements Lewis G D et al. Circulation 2007;116:1555-1562

  36. Quantitative Analysis Lewis G D et al. Circulation 2007;116:1555-1562

  37. Quantitative Analysis Lewis G D et al. Circulation 2007;116:1555-1562

  38. Qualitative Analysis Lewis G D et al. Circulation 2007;116:1555-1562

  39. Sildenafil • Improved first pass RVEF • Improved NYHA class in over 50% of Sildenafil and 13% in placebo • Conclusions • Improvements in both quantitative and qualitative measurements in CHF patients with PH Lewis G D et al. Circulation 2007;116:1555-1562

  40. PH and Cardiac Transplantation • TPG and PVR Increased mortality • Barrier to successful transplantation • ISHLT guidelines -- Vasodilator Challenge • mPA > 50 mmHg AND • TPG > 15 mmHG OR • PVR > 3 Wood Units

  41. Sildenafil in Class IV CHF Pre-Transplant • Case Series of 6 patients awaiting transplant • All had TPG > 15 mmHg Jabbour A et al. Eur J Heart Fail 2007;9:674-677

  42. TPG Jabbour A et al. Eur J Heart Fail 2007;9:674-677

  43. PVR Jabbour A et al. Eur J Heart Fail 2007;9:674-677

  44. Sildenafil in addition to vasodilator challenge enabled sufficient decrease in PVR and TPG to enable transplantation Jabbour A et al. Eur J Heart Fail 2007;9:674-677

  45. Mechanical Support

  46. Pulsatile LVAD • Retrospective Analysis of 69 LVAD patients • No significant difference in pre-LVAD hemodynamics • 30% Developed RV dysfunction (21/69) • Prolonged inotropic support, longer HD, Increased transfusions, mortality • RVAD needed post-operative • 1 patient Kavarana M. N. et al.; Ann Thorac Surg 2002;73:745-750

  47. Peri-Operative Kavarana M. N. et al.; Ann Thorac Surg 2002;73:745-750

  48. Transplantation Kavarana M. N. et al.; Ann Thorac Surg 2002;73:745-750

  49. Continuous Flow HM-II • 40 LVAD patients -- Single Center • Pre and Post LVAD implant • Hemodynamics • Echocardiographic indices

  50. Continuous Flow HM-II Pre-LVAD Post-LVAD mean mean PCWP 24.5 12.9 TPG 12.7 9.4 PVR 3.7 2.1 C.I. 1.9 2.5 All p-values < .001

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