Type II Pulmonary Hypertension: Pulmonary Hypertension due to

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  • 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

    Heart Failure Center

    Hadassah University Hospital

  • 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.

  • Types of Pulmonary Hypertension

    Type 1

    Type 4

    Type 3

    Type 2

  • 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

  • Pathophysiology

    Abnormalities of the left heart:

    Elevated left-sided filling pressures

    Passive congestion:

    Pulmonary venous hypertension

    Endothelial dysfunction:

    Reactive vasoconstriction

    Vascular Remodeling

    Long-standing PVH

    Long-standing Vasoconstriction

  • Mechanism of PHT

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

  • 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

    DPG

  • 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

  • PHT in Patients with Heart Failure High prevalence of reactive PHT (>50%)

    Schwartzenberg S, J Am Coll Cardiol. 2012

  • Prognosis of Pulmonary Hypertension in Patients With Heart Failure

    Lam CS, J Am Coll Cardiol. 2009 Abramson SV, Ann Intern Med. 1992

  • Prognosis of Pulmonary Hypertension in Patients With Heart Failure

    Kjaergaard, Am J Cardiol 2007

  • Relation between PAP and RV Function in Patients With Heart Failure

    Ghio S, J Am Coll Cardiol. 2001

  • Importance of RV Function: Independent and Additive Ominous Prognosis

    Ghio S, J Am Coll Cardiol. 2001

    High PAP/low RVEF

    normal PAP/preserved RVEF

    normal PAP/low RVEF high PAP/preserved RVEF

    RV failure - Extremely Unfavorable Prognosis

  • 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

  • Pharmacological Therapies

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

  • 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

  • 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