heart and lungs philippe heart... · 2014-05-22 · heart and lungs philippe meyer, md heart...

Heart and Lungs

Philippe Meyer, MD

Heart Failure and Cardiovascular rehabilitation Cardiology Service University Hospital of Geneva, Switzerland [email protected]

SGK Herbsttagung – Zürich - 22.11.2012

Anatomical proximity

Common pulmonary circulation

There are many conditions resulting from heart-lungs interactions in heart failure

Left-sided pulmonary hypertension

Sleep-disordered breathing

Acute pulmonary edema

Cor pulmonale

Restrictive lung disease

Right ventricular failure post-PE

Plan

Definitions and epidemiology

Pathophysiology

Clinical implications

Therapies

Definition of pulmonary hypertension (PH)

Mean pulmonary artery pressure (PAP)

≥25 mmHg

at rest

Galie N et al. Eur Heart J. 2009;30:2493-2537


Most common form of PH

Hemodynamic definitions of PH due to left heart disease


Definitions Characteristics

Post-capillary PH Mean PAP ≥25 mmHg at rest

PCWP >15 mmHg

«Passive» PH in heart failure

3.5 l/min

CO

• Transpulmonary gradient (TPG) = Mean PAP - Pulmonary Capillary

Wedge Pressure (PCWP) = 7 mmHg

TPG

(PCWP)

«Reactive or «out of proportion» PH in heart failure

4.6 l/min

CO

• Transpulmonary gradient (TPG) = Mean PAP - Pulmonary Capillary

Wedge Pressure (PCWP) = 23 mmHg

TPG

(PCWP)





PCWP >15 mmHg

Passive PH TPG ≤12 mmHg

PVR ≤3 WU

Reactive (out of proportion) PH TPG >12 mmHg

PVR >3 WU

The concept of «reversibility» of PH

• Assessment of PH reversibility by different pharmacological agents during right heart catheterization is useful for stratifying risk before heart transplantation

• PH is considered reversible if PVR can be lowered to ≤2.5 Wood units (WU) without systemic hypotension (SBP >85 mmHg)



Haddad F Prog Cardiovasc Dis. 2011;54:154-167



PCWP >15 mmHg

Passive PH TG ≤12 mmHg

PVR ≤3 WU

Reactive (out of proportion) PH TG >12 mmHg

PVR >3 WU

Reversible (vasoreactive) PH PVR ≤2.5 WU

Syst BP >85 mmHg

Non-reversible (non vasoreactive) PH PVR >2.5 WU or

Syst BP ≤85 mmHg

PH is highly prevalent in patients with HF

• ~40% in HF with reduced LVEF (NYHA functional class III-IV)

– Passive PH in 2/3 to 3/4 of cases

• 50-80% in HF with preserved LVEF

depending on populations and PH diagnostic criteria used


Haddad F Prog Cardiovasc Dis. 2011;54:154-167

Plan


Pathophysiology


Therapies

Pathophysiology of PH in heart failure

Left-sided HF

LV filling pressures

«Passive» PH

gas exchange

STRUCTURAL CHANGES (AT-II, TNF, ET1, hypoxia)

VASOREACTIVITY ( ET1, NO)

RV failure

«Reactive» PH

Genes

Genes

Plan


Pathophysiology


Therapies

PH was repeatedly associated with mortality in HF

Study Patients Criteria Follow-up HR for death

Abramson 1992

(n=108)

Outpatient HFrEF

NYHA I–IV

TR velocity

>2.5 m/s 28 months 3.35

Cappola 2002

(n=1134) Outpatient HFrEF

PVR

>3 WU 48 months

Unadjusted

HR 2.3

Lam 2009

(n=244) Outpatient HFpEF PASP 34 months

1.2 per 10 mmHg

PASP

Aronson 2011

(n=242)

Hospitalized HFrEF

NYHA II

mPAP

>25 mmHg 6 months

2.8 (passive PH)

4.8 (reactive PH)

Szwejkowski

2012 (n=1612)

Outpatient HFrEF

Loop diuretics PASP 2.8 years

1.06 per 5 mmHg

PASP

Bursi 2012

(n=1049)

Outpatient HFrEF

+ HFpEF

PASP

>54 mmHg 2.7 years 2.07

Bursi F et al. J Am Coll Cardiol 2012;59:222-31

• 1049 ambulatory HF patients, irrespective of LVEF

• PASP estimated by Doppler echo

• Follow-up 2.7 ± 1.9 years

Adjusted HR = 2.07

PH reversibility and prognosis pre-transplantation

• 298 patients, NYHA III-IV, LVEF, 3-months follow-up post-tx

• PH reversibility assessed by nitroprusside during RHC

Costard-Jäckle A, et al. J Am Coll Cardiol 1992;19:48e54.

PVR >2.5 WU Deaths: 17.9%

PVR <2.5 WU

Deaths: 6.9%

PVR <2.5 WU

PVR >2.5 WU

Deaths: 40.6%

SBP <85 mmHg

Deaths: 27.5%

SBP >85 mmHg

Deaths: 3.8%

Baseline RHC After Nitroprusside

Listing criteria for cardiac transplantation

• PH and elevated PVR should be considered as a relative contraindication to cardiac transplantation when PASP is >60 mmHg in the presence of PVR >5 WU or TPG >16-20 mmHg

• Patients can be considered eligible if PH is reversible by testing without systemic hypotension

Mehra MR et al. J Heart Lung Transplant 2006;25:1024e42.

RV dysfunction is also an established predictor of mortality in HF

Guazzi M et al. Nat. Rev. Cardiol. 2010;7:648–659

• 2008 patients, 60 years, 79% men

• NYHA III-IV, LVEF 25%

• RVEF assessed by radionuclide ventriculography

Circulation. 2010;121:252-258.

Adjusted HR=1.32 P=0.034)

Adjusted HR=1.39 (P=0.007)

Plan


Pathophysiology


Therapies

«General» HF therapy

• Several studies have shown that PH may regress after optimization of traditional evidence-based HF therapies (drugs, devices)

• The most spectacular effect on PAP reduction has been reported after LVAD implantation in several studies


• HeartMate II «bridge to transplant», mean 281 days

• RHC at 3 months post-LVAD and 1 months post-tx

J Thorac Cardiovasc Surg 2010;140:447-452.

Selected clinical trials of pulmonary vasodilators in HF

Study Patients Drug Outcomes

Califf 1997

(n=471)

HFrEF

NYHA III–IV Eposprostenol Strong trend towards mortality

Kalra 2002

(n=1613)

HFrEF

NYHA iii-IV Bosentan

No clinical improvement fluid retention

Kaluski 2001

(n=94)

HFrEF

NYHA III–IV Bosentan

No hemodynamic/echo changes More serious adverse events

Anand 2004

(n=642)

HFrEF

NYHA II–IV Darusentan

No change in cardiac remodeling

or outcome

Kaluski 2003

Acute

pulmonary

edema

Tezosentan No change in SaO2

Outcome worse with higher dose

Lewis 2007

(n=34)

HFrEF

NYHA II-IV Sildenafil

PAP

Peak VO2, 6-min walk test

hospitalizations

Guazzi 2011

(n=44) HFpEF Sildenafil

Mean PAP and PVR

RV function

Quality of life


• Clinical HF, diastolic dysfunction, LVEF >50%, and PASP >40 mmHg

• Sildenafil 3 x 50 mg vs placebo

Circulation. 2011;124:164-174.

PVR (WU)

But…

Phosphodiesterase-5 inhibitors should still be

considered as experimental since their

benefits have not been proved in a large RCT

with clinical endpoints

Promising novel agents

• Direct stimulator of soluble guanylate cyclase (sGC)

• Phase 2 clinical trial in patients with HFrEF and mPAP ≥25 mmHg

• Presented at AHA congress on November 5th

• No effect on mean PAP but increase in cardiac output

• Good safety profile

Conclusions

• PH due to left-sided heart failure is the most common cause of PH

• Left-sided PH and RV dysfunction are independent predictors of poor outcomes in patients with chronic HF

• Most of selective pulmonary vasodilators were disappointing in HF but patients selection may have been inadequate

• Promising results have been observed with the use of PDE-5 inhibitors but larger clinical trials are needed

• Further research is needed on the pathophysiology of left-sided PH in order to improve its management

Thank you for your attention

Philippe Meyer, MD

Heart Failure and Cardiovascular rehabilitation Cardiology Service University Hospital of Geneva, Switzerland [email protected]

SGK Herbsttagung – Zürich - 22.11.2012

heart and lungs philippe heart... · 2014-05-22 · heart and lungs philippe meyer, md heart...

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