Pulmonary Hypertension: Definition and Unmet Needs

Transcription

1 Heart Failure Center Hadassah University Hospital Pulmonary Hypertension: Definition and Unmet Needs Israel Gotsman The Heart Failure Center Hadassah University Hospital

2 I DO NOT have a financial interest/ arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

3 Types of Pulmonary Hypertension Type 3 Type 4 Type 1 Type 2

4 Distribution of PHT types 4. CTEPH 2.1% 5. Misc 1. PAH 5.2% 4.6% 3. Lung Dis 11.3% 2. Left Heart Dis 76.7% 1. PAH 2. Left Heart Dis 3. Lung Dis 4. CTEPH 5. Misc Strange, Gabbay. Heart. 2012

5 Hemodynamic Definition of PHT Mea PAP PCWP 15 mmhg PVR >3 WU Pre-capillary PH PAH Lung Disease CTEPH Multifactorial 5 Hg PCWP > 15 mmhg DPG <7 mmhg and/or PVR WU DPG 7 Hg and/or PVR >3 WU Isolated Post-capillary PH (Passive) Combined Post & Pre-capillary PH (Reactive) DPG = Diastolic pressure gradient (diastolic PAP mean PAWP) Reversible with treatment Fixed

6 World Health Organization (WHO) [Dana Point] Clinical Classification of Pulmonary Hypertension 1. Pulmonary arterial hypertension 2. PH due to left heart disease 3. PH due to lung diseases and/or Hypoxia 4. Chronic thromboembolic PH 5. PH - multifactorial mechanisms

7 World Health Organization (WHO) [Dana Point] Clinical Classification of Pulmonary Hypertension 1. Pulmonary arterial hypertension Drug therapy - prostacyclins, endothelin RA, PDE5 inhibitors 2. PH due to left heart disease Reduce left sided pressures, Drug therapy? 3. PH due to lung diseases and/or Hypoxia Treat lung disease, Limited place for drugs 4. Chronic thromboembolic PH Pulmonary thromboendarterectomy Drug therapy 5. PH - multifactorial mechanisms

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9 Pathophysiology Mechanism of PHT Abnormalities of the left heart: Elevated left-sided filling pressures Passive congestion: Pulmonary venous hypertension Long-standing PVH Endothelial dysfunction: Reactive vasoconstriction Long-standing Vasoconstriction Vascular Remodeling Endothelial dysfunction: imbalance between NO and endothelin-1 (ET1) signaling causes abnormalities in smooth muscle tone

10 PHT due to Left Heart Disease Most common cause of PHT Highly prevalent complication of LHD Related to disease severity Worse symptoms and reduced FC Negative impact on outcome Clinical Characteristics: Older, female, higher prevalence of cardiovascular co-morbidities and metabolic syndrome

11 PHT in Patients with Heart Failure High prevalence of reactive PHT (>50%) Schwartzenberg S, J Am Coll Cardiol. 2012

12 Prognosis of Pulmonary Hypertension in Patients With Heart Failure Lam CS, J Am Coll Cardiol Abramson SV, Ann Intern Med. 1992

13 Relation between PAP and RV Function in Patients With Heart Failure Importance of RV Function: Independent and Additive Ominous Prognosis Normal PAP/ preserved RVEF normal PAP/ low RVEF High PAP/ preserved RVEF High PAP/ low RVEF Ghio S, J Am Coll Cardiol RV failure - Extremely Unfavorable Prognosis

14 Pharmacological Therapies Short-term studies demonstrate favorable hemodynamic effects Several trials have shown worsening morbidity or mortality in patients with systolic LHF

15 RELAX trial in HFPEF Negative Multicenter study - PDE-5 inhibition in HFPEF No effect on exercise capacity, clinical status, quality of life, left ventricular remodeling, diastolic function parameters, or pulmonary artery systolic pressure Renal function worsened NT-proBNP, endothelin-1, and uric acid levels increased More withdrew consent, died, or were too ill to perform the cardiopulmonary exercise test Higher incidence of vascular adverse events PDE-5 inhibitor (sildenafil) did not have clinical benefit Redfield MM, JAMA. 2013

16 Therapy for PHT-LHD Reduce left sided pressures: Optimized therapy of heart failure Control Risk factors: CVD and metabolic syndrome Treat associated disorders COPD, sleep apnea & PE Timely treatment of valve (Mitral) Disease Cardiac resynchronization therapy LV Assist Device / transplantation in appropriate patients Direct therapy An unmet need

17 Thank You

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19 Type II Pulmonary Hypertension: Pulmonary Hypertension due to Left Heart Disease World Health Organization (WHO) [Dana Point] Clinical Classification of Pulmonary Hypertension 1. Pulmonary arterial hypertension 2. PH due to left heart disease 2.1 Left ventricular systolic dysfunction 2.2 Left ventricular diastolic dysfunction 2.3 Valvular disease Congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies 2.5 Congenital/acquired pulmonary veins stenosis PH due to lung diseases and/or Hypoxia Chronic thromboembolic PH PH with unclear multifactorial mechanisms

20 PHT due to LHD - Definition Mea PAP 5 Hg + PCWP > 15 mmhg Isolated post-capillary (Passive) DPG <7 Hg [TPG and/or PVR WU Hg] Combined post & pre-capillary (Reactive) DPG 7 Hg [TPG> and/or PVR >3 WU Reversible with treatment Hg] Fixed DPG = Diastolic pressure gradient (diastolic PAP mean PAWP) TPG = Transpulmonary pressure gradient (mean PAP mean PAWP)

21 Importance of RV Function: Independent and Additive Ominous Prognosis normal PAP/preserved RVEF normal PAP/low RVEF high PAP/preserved RVEF High PAP/low RVEF Ghio S, J Am Coll Cardiol RV failure - Extremely Unfavorable Prognosis

22 Mechanism of PHT Endothelial dysfunction: imbalance between NO and endothelin-1 (ET1) signaling causes abnormalities in smooth muscle tone

23 Prognosis of Pulmonary Hypertension in Patients With Heart Failure Kjaergaard, Am J Cardiol 2007

24 Therapy for PHT-LHD Treat underlying condition: Timely repair of valvular heart disease Optimizing therapy and volume status in HFREF Control Risk factors for cardiovascular diseases and metabolic syndrome. Identify and treat concomitant disorders leading to PHT COPD, sleep apnea and PE Implantation of an LV assist device