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