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 3. Chronic
Hypoxemia
4.
Thromboembolic
2. Left Heart
Disease
5.
-Sarcoid, fibrosing
Miscelaneous
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
RVS
P
RVS
P
Congestive Heart Failure
Volume 17, Issue 4, pages 189-198,
21 JUL 2011 DOI: 10.1111/j.17517133.2011.00234.x
• Independent predictor of mortality
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
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 Output
Normal 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 PH
Elevated mPA solely attributed to
PCWP
TPG < 10-12
Tx Based on
Traditional CHF
management
Active or Reactive
PH
Elevated mPA beyond PCWP
TPG> 10-12
Tx Based on Traditional
CHF management ??
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
Pulmonary
Remodeling
Does not normalize with
traditional
CHF treatments
“Fixed” Pulmonary
Arteriopathy
Ultimately
RV
Failure
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
VCU/MCV -- NO challenge
Reactive Changes
with Fixed PH:
--Persistent PVR >=2.5 WU
or
--PVR < 2.5 WU secondary to
SBP <85 mmHg
Right Ventricular
Failure
RV
Hypertrophy
RV
Dilation
Flattening of Interventricular
Septum -- D Shaped LV
RA
Enlargement
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
Flola
n
Bosentan /
Darusentan
Moraes D L et al. Circulation 2000;102:1718-1723
Prostacycli
n
Sildena
fil
Role for pulmonary
vasodilators?
• Prostanoids -- FIRST Trial -- Flolan
• Endothelial Receptor Antagonists
REACH and ENABLE trials -- Bosentan
• Phosphodiesterase Inhibitors -Sildenafil
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
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
ENABLE
Endothelin Antagonist Bosentan for Lowering Cardiac Events in Heart
Failure
• 1600 Patients Bosentan (lower dose) vs
Placebo
• Increased CHF exacerbations
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 HMII
• 40 LVAD patients -- Single Center
• Pre and Post LVAD implant
• Hemodynamics
• Echocardiographic indices
Continuous Flow HMII
PCW
P
TP
G
PV
R
C.I
.
PreLVAD
24.5
PostLVAD
12.9
12.7
9.4
3.7
2.1
1.9
2.5
mea
n
mea
n
All p-values <
.001
Continuous Flow HMII
• RV failure after LVAD
• >14 days inotropic support or
RVAD
• 5% (2/40)
• At 6 Months 37/40 alive or transplanted
Continuous Flow HMII
• 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
Passive PH
TPG < 12 mmHg
RV dysfunction
Traditional
Medical Therapy
•ACEi / ARB/ Aldosterone
Antagonists
•Beta Blockade / Diuretic
•CRT
Reactive PH
TPG > 12
mmHg
Advanced
Treatment Options
•Sildenafil ??
•LVAD vs TAH