Pulmonary Hypertension and Congestive Heart Failure
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Transcript of Pulmonary Hypertension and Congestive Heart Failure
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Pulmonary Hypertension and
Congestive Heart Failure
Stephen L. Rennyson MDAugust 11, 2011
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Pulmonary Hypertension
• Mean Pulmonary Artery Pressure (mPAP)
• > 25 mmHg
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WHO Classification of Pulmonary Hypertension
1. Pulmonary Arterial Hypertension
2. Left Heart Disease3. Chronic
Hypoxemia
4. Thromboembol
ic
5. Miscelaneou
s-Sarcoid, fibrosing
mediastinitis
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Relationship of CHF and PH
Passive Congestion (Elevated PCWP)
Increased LVEDP (PCWP)
Pre - Capillary vs Post - Capillary PH
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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
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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
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Survival after Cardiac
Transplantation
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
✴Elevated PAP and Low RV
function
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Cardiac Catheterization
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Hemodynamic Assessment
• Right Heart Catheterization
• RA, RV, PAP, PCWP
• Thermodilution and Fick
End Expiration -- Best approximate of atmospheric pressure
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Transpulmonary Gradient (TPG)
Change in pressure across the pulmonary circulation
• mPA - PCWP
• Normal TPG < 10 mmHg
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Pulmonary Vascular
Resistance
• Resistance to flow that must be overcome to push blood through the system
• Ohms Law:
• mPA - PCWP
• Cardiac OutputNormal Values of < = to 1.5 Wood Units
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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
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Post Capillary PH out of proportion
• Use of TPG and PVR
• TPG > 10-12 mmHg
• PVR > 1.5 wood units
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PH out of proportion
Passive PHElevated mPA solely attributed to
PCWPTPG < 10-12
Active or Reactive PH
Elevated mPA beyond PCWP
TPG> 10-12
Tx Based on Traditional CHF management ??
Tx Based on Traditional CHF management
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Reactive PHChronic Venous hypertension
Longstanding Advanced
Heart Failure
Pulmonary Vascular Remodeling
•Elastic Fibers•Intimal Fibrosis•Medial Hypertrophy
Mediated by Endothelin
Changes -- Indistinguishable from PAH
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Pulmonary Remodeling
Does not normalize with traditional
CHF treatments
Ultimately RV Failure
“Fixed” Pulmonary Arteriopathy
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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
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Vasodilator Challenge
Reactive Changes with Fixed PH:
--Persistent PVR >=2.5 WUor
--PVR < 2.5 WU secondary to SBP <85 mmHg
VCU/MCV -- NO challenge
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Right Ventricular Failure
RV Hypertrophy
RV Dilation
RA Enlargement
Flattening of Interventricular Septum -- D Shaped LV
Tricuspid Regurgitation
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Right Ventricular Evaluation
•Transthoracic Echocardiography
•Qualitative
•Quantitative
•Tricuspid Annular Peak Systolic Excursion (TAPSE) -- > M-mode
•Tissue Doppler
•First Pass (RVEF)
•MRI
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TAPSE
American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 1034-1041, (2006)
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TAPSE (< 1.8 cm)
American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 1034-1041, (2006)
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TAPSE (< 1.8 cm)
American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 1034-1041, (2006)
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TAPSE (< 1.8 cm)
American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 1034-1041, (2006)
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Medical Management
Moraes D L et al. Circulation 2000;102:1718-1723
Bosentan / Darusentan
Sildenafil
Flolan
Prostacyclin
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Role for pulmonary vasodilators?
• Prostanoids -- FIRST Trial -- Flolan
• Endothelial Receptor Antagonists REACH and ENABLE trials -- Bosentan
• Phosphodiesterase Inhibitors -- Sildenafil
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FIRST
• 471 patients class III/IV
• Improved Hemodynamics
• Increased CI / Decreased PVR and PCWP
• Exercise Tolerance and QOL
• No Change
• Increased Mortality
• Contraindicated
Flolan International Randomized Survival Trial
Am Heart J 1997;134:44-54
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REACH
• 370 Patients
• High dose Bosentan vs Placebo
• Trial Stopped Early
• Increase in early CHF exacerbations
• Elevated Transaminase Levels
Research of Endothelin Antagonists in Chronic Heart Failure
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ENABLE
• 1600 Patients Bosentan (lower dose) vs Placebo
• Increased CHF exacerbations
Endothelin Antagonist Bosentan for Lowering Cardiac Events in Heart Failure
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Phosphodiesterase Inhibitors
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Sildenafil
• No large scale clinical trials
• Acute Hemodynamic Trials
• Long Term Hemodynamics
• Quality of Life Trials
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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
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Duration of Effect
NO Alone
NO and Sildenafil
Lepore JJ, Maroo A, Bigatello LM, et al. Chest. 2005;127:1647-1653
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Acute Changes
Lepore JJ, Maroo A, Bigatello LM, et al. Chest. 2005;127:1647-1653
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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
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Quantitative Analysis
Lewis G D et al. Circulation 2007;116:1555-1562
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Quantitative Analysis
Lewis G D et al. Circulation 2007;116:1555-1562
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Qualitative Analysis
Lewis G D et al. Circulation 2007;116:1555-1562
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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
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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
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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
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TPG
Jabbour A et al. Eur J Heart Fail 2007;9:674-677
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PVR
Jabbour A et al. Eur J Heart Fail 2007;9:674-677
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• 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
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Mechanical Support
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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
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Peri-Operative
Kavarana M. N. et al.; Ann Thorac Surg 2002;73:745-750
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Transplantation
Kavarana M. N. et al.; Ann Thorac Surg 2002;73:745-750
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Continuous Flow HM-II
• 40 LVAD patients -- Single Center
• Pre and Post LVAD implant
• Hemodynamics
• Echocardiographic indices
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Continuous Flow HM-II
PVR
3.7 2.1
C.I.
PCWPTPG
24.5 12.9
1.9 2.5
12.7 9.4
Post-LVAD
Pre-LVAD
All p-values < .001
mean
mean
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Continuous Flow HM-II
• RV failure after LVAD
• >14 days inotropic support or RVAD
• 5% (2/40)
• At 6 Months 37/40 alive or transplanted
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Continuous Flow HM-II
• RV failure can be treated effectively with continuous flow left ventricular assist devices
• Bridge to transplant patients
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Biventricular Support (TAH) --
Syncardia
• An option for severe bi-ventricular failure with significant Reactive PH
• Effective Bridge to transplantation
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Pulmonary Circulation After
TAH• Single center retrospective study (VCU/MCV)
• 40+ patients
• Evaluation of hemodynamics pre and post TAH
• Pulsatile mechanism vs Continuous Flow of LVAD
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Pulmonary Hypertension secondary to CHF
(Systolic and Diastolic)
Chronic post-capillary PH
Pulmonary Vascular Remodeling
RV dysfunction
Advanced Treatment Options
TraditionalMedical Therapy
•Sildenafil ??•LVAD vs TAH
Passive PHTPG < 12 mmHg
Reactive PHTPG > 12
mmHg
•ACEi / ARB/ Aldosterone Antagonists•Beta Blockade / Diuretic •CRT