Pulmonary Hypertension and Congestive Heart Failure
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Transcript of Pulmonary Hypertension and Congestive Heart Failure
Pulmonary Hypertension and
Congestive Heart Failure
Stephen L. Rennyson MDAugust 11, 2011
Pulmonary Hypertension
• Mean Pulmonary Artery Pressure (mPAP)
• > 25 mmHg
WHO Classification of Pulmonary Hypertension
1. Pulmonary Arterial Hypertension
2. Left Heart Disease3. Chronic
Hypoxemia
4. Thromboembol
ic
5. Miscelaneou
s-Sarcoid, fibrosing
mediastinitis
Relationship of CHF and PH
Passive Congestion (Elevated PCWP)
Increased LVEDP (PCWP)
Pre - Capillary vs Post - Capillary PH
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
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
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
Cardiac Catheterization
Hemodynamic Assessment
• Right Heart Catheterization
• RA, RV, PAP, PCWP
• Thermodilution and Fick
End Expiration -- Best approximate of atmospheric pressure
Transpulmonary Gradient (TPG)
Change in pressure across the pulmonary circulation
• mPA - PCWP
• Normal TPG < 10 mmHg
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
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
Post Capillary PH out of proportion
• Use of TPG and PVR
• TPG > 10-12 mmHg
• PVR > 1.5 wood units
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
Reactive PHChronic Venous hypertension
Longstanding Advanced
Heart Failure
Pulmonary Vascular Remodeling
•Elastic Fibers•Intimal Fibrosis•Medial Hypertrophy
Mediated by Endothelin
Changes -- Indistinguishable from PAH
Pulmonary Remodeling
Does not normalize with traditional
CHF treatments
Ultimately RV Failure
“Fixed” Pulmonary Arteriopathy
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
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
Right Ventricular Failure
RV Hypertrophy
RV Dilation
RA Enlargement
Flattening of Interventricular Septum -- D Shaped LV
Tricuspid Regurgitation
Right Ventricular Evaluation
•Transthoracic Echocardiography
•Qualitative
•Quantitative
•Tricuspid Annular Peak Systolic Excursion (TAPSE) -- > M-mode
•Tissue Doppler
•First Pass (RVEF)
•MRI
TAPSE
American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 1034-1041, (2006)
TAPSE (< 1.8 cm)
American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 1034-1041, (2006)
TAPSE (< 1.8 cm)
American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 1034-1041, (2006)
TAPSE (< 1.8 cm)
American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 1034-1041, (2006)
Medical Management
Moraes D L et al. Circulation 2000;102:1718-1723
Bosentan / Darusentan
Sildenafil
Flolan
Prostacyclin
Role for pulmonary vasodilators?
• Prostanoids -- FIRST Trial -- Flolan
• Endothelial Receptor Antagonists REACH and ENABLE trials -- Bosentan
• Phosphodiesterase Inhibitors -- Sildenafil
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
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
ENABLE
• 1600 Patients Bosentan (lower dose) vs Placebo
• Increased CHF exacerbations
Endothelin Antagonist Bosentan for Lowering Cardiac Events in Heart Failure
Phosphodiesterase Inhibitors
Sildenafil
• No large scale clinical trials
• Acute Hemodynamic Trials
• Long Term Hemodynamics
• Quality of Life Trials
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
Duration of Effect
NO Alone
NO and Sildenafil
Lepore JJ, Maroo A, Bigatello LM, et al. Chest. 2005;127:1647-1653
Acute Changes
Lepore JJ, Maroo A, Bigatello LM, et al. Chest. 2005;127:1647-1653
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
Quantitative Analysis
Lewis G D et al. Circulation 2007;116:1555-1562
Quantitative Analysis
Lewis G D et al. Circulation 2007;116:1555-1562
Qualitative Analysis
Lewis G D et al. Circulation 2007;116:1555-1562
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
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
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
TPG
Jabbour A et al. Eur J Heart Fail 2007;9:674-677
PVR
Jabbour A et al. Eur J Heart Fail 2007;9:674-677
• 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
Mechanical Support
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
Peri-Operative
Kavarana M. N. et al.; Ann Thorac Surg 2002;73:745-750
Transplantation
Kavarana M. N. et al.; Ann Thorac Surg 2002;73:745-750
Continuous Flow HM-II
• 40 LVAD patients -- Single Center
• Pre and Post LVAD implant
• Hemodynamics
• Echocardiographic indices
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
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
Continuous Flow HM-II
• RV failure can be treated effectively with continuous flow left ventricular assist devices
• Bridge to transplant patients
Biventricular Support (TAH) --
Syncardia
• An option for severe bi-ventricular failure with significant Reactive PH
• Effective Bridge to transplantation
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
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