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 <7 mmHg [TPG≤12 mmHg] and/or

PVR ≤3 WU

Combined post & pre-capillary (Reactive)

Reversible with treatment Fixed

DPG = Diastolic pressure gradient (diastolic PAP – mean PAWP) TPG = Transpulmonary pressure gradient (mean PAP – mean PAWP)

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