Type II Pulmonary Hypertension: Pulmonary Hypertension due to Left Heart Disease

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1 Heart Failure Center Hadassah University Hospital Type II Pulmonary Hypertension: Pulmonary Hypertension due to Left Heart Disease Israel Gotsman MD The Heart Failure Center, Heart Institute Hadassah University Hospital, Jerusalem, Israel

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 4 Type 3 Type 1 Type 2

4 World Health Organization (WHO) [Dana Point] Clinical Classification of Pulmonary Hypertension 1. Pulmonary arterial hypertension 2. Pulmonary hypertension due to left heart disease 2.1 Left ventricular systolic dysfunction 2.2 Left ventricular diastolic dysfunction 2.3 Valvular disease 2.4 Congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies 2.5 Congenital/acquired pulmonary veins stenosis 3. Pulmonary hypertension due to lung diseases and/or Hypoxia 4. Chronic thromboembolic pulmonary hypertension 5. Pulmonary hypertension with unclear multifactorial mechanisms

5 Pathophysiology Abnormalities of the left heart: Elevated left-sided filling pressures Long-standing PVH Long-standing Vasoconstriction Passive congestion: Pulmonary venous hypertension Endothelial dysfunction: Reactive vasoconstriction Vascular Remodeling

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

7 PHT due to LHD - Definition Mean PAP 25 mmhg + PCWP > 15 mmhg Isolated post-capillary (Passive) DPG <7 mmhg [TPG 12 mmhg] and/or PVR 3 WU Combined post & pre-capillary (Reactive) DPG 7 mmhg [TPG>12 mmhg] and/or PVR >3 WU Reversible with treatment Fixed DPG = Diastolic pressure gradient (diastolic PAP mean PAWP) TPG = Transpulmonary pressure gradient (mean PAP mean PAWP)

8 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

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

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

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

12 Relation between PAP and RV Function in Patients With Heart Failure Ghio S, J Am Coll Cardiol. 2001

13 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

15 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

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

17 RELAX trial 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

18 Therapy for PHT-LHD Reduce left sided pressures: Optimized therapy of heart failure Timely treatment of valve (Mitral) Disease Cardiac resynchronization therapy LV Assist Device / transplantation in appropriate patients Direct therapy An unmet need

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