Pulmonary Hypertension

, Gregory D. Lewis2 and Gregory D. Lewis3



(1)
Harvard Medical School Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

(2)
Mass General Cardiopulmonary Exercise Laboratory, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

(3)
Harvard Medical School, Boston, USA

 



Introduction

Definitions

Diagnostic Work Up

Group 1—Pulmonary Hypertension

Group II—Pulmonary Venous Hypertension (Due to Left Heart Dysfunction)

Group III—Hypoxia Associated Pulmonary Hypertension

Group IV—Thromboembolic Pulmonary Hypertension

Pulmonary Hypertension in the Cardiac Surgery Patient

References


Abstract

The right ventricular-pulmonary vascular unit is a low resistance, high compliance system that is normally capable of accommodating large increases in blood flow with a minimal increment in pressure. The development of elevated pulmonary arterial pressures, either in unselected populations or in individuals with a variety of cardiopulmonary diseases, is increasingly recognized to be associated with a markedly increased risk of mortality. Regardless of the etiology, pulmonary hypertension leads to right ventricular dysfunction that is closely associated with impaired exercise capacity, renal and hepatic dysfunction. This chapter will briefly review the epidemiology and pathophysiology of pulmonary hypertension (PH) in addition to current diagnostic and treatment approaches with particular emphasis on PH arising in the setting of other cardiovascular diseases.


Abbreviations


6 MW

6 Minute Walk

APAH

Associated with Pulmonary Arterial Hypertension

BMP

Bone Morphogenic Protein

CCB

Calcium Channel Blockers

COPD

Chronic Obstruction Lung Disease

CTEPH

Chronic Thromboembolic Pulmonary Hypertension

DVT

Deep Venous Throbosis

FPAH

Familial Pulmonary Arterial Hypertension

HFpEF

Heart Failure with preserved Ejection Fraction

IPAH

Idiopathic Pulmonary Arterial Hypertension

JVP

Jugular Venous Pressure

LFT

Liver Function Test

LVEF

Left Ventricular Ejection Fraction

mPAP

Mean Pulmonary Artery Pressure

NO

Nitric Oxide

NYHA

New York Heart Association

PA

Pulmonary Artery

PAH

Pulmonary Arterial Hypertension

PAP

Pulmonary Artery Pressure

PCH

Pulmonary Capillary Hemangiomatosis

PCWP

Pulmonary Capillary Wedge Pressure

PDE-5

Phosphodiesterase-5

PE

Pulmonary Embolism

PH

Pulmonary Hypertension

PVOD

Pulmonary Veno-Occlusive Disease

PVR

Pulmonary Vascular Resitance

RV

Right Ventricle

RVEF

Right Ventricular Ejection Fraction

TAPSE

Tricuspid Annular Plane Systolic Excursion

TTE

Transthoracic echocardiogram

WHO

World Health Organization



Introduction


The right ventricular-pulmonary vascular unit is a low resistance, high compliance system that is normally capable of accommodating large increases in blood flow with a minimal increment in pressure. The development of elevated pulmonary arterial pressures, either in unselected populations or in individuals with a variety of cardiopulmonary diseases, is increasingly recognized to be associated with a markedly increased risk of mortality. Regardless of the etiology, pulmonary hypertension leads to right ventricular dysfunction that is closely associated with impaired exercise capacity, renal and hepatic dysfunction. This chapter will briefly review the epidemiology and pathophysiology of pulmonary hypertension (PH) in addition to current diagnostic and treatment approaches with particular emphasis on PH arising in the setting of other cardiovascular diseases.

1.

Overview of pulmonary hypertension

 

2.

Diagnostic work up

 

3.

WHO Group Classification with particular attention to:

(a)

Idiopathic Arterial Pulmonary Hypertension

 

(b)

Pulmonary Venous Hypertension

 

(c)

Hypoxia Associated Pulmonary Hypertension

 

(d)

Chronic Thromboembolic Pulmonary Hypertension

 

 


Definitions




A.

Pulmonary Hypertension (PH)



  • Definition: An abnormally high blood pressure within the arteries of the lungs


  • Hemodynamic diagnostic criteria



    • Mean pulmonary artery pressure > 25 mmHg.

 

B.

Pulmonary arterial hypertension (PAH)



  • Definition: A syndrome caused from restricted blood flow through the pulmonary circulation leading to elevation in pulmonary resistance and subsequent right heart failure. Hemodynamic characteristics include



    • Mean pulmonary artery pressure (PAP) >25 mmHg and


    • Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure ≤15 mmHg and


    • Pulmonary vascular resistance (PVR) >3 Woods units

 

C.

Pathology



  • Elevated PVR due to


  • loss of vascular luminal cross sectional area due to vascular remodeling from excessive cell proliferation and decreased rates of apoptosis


  • impaired endothelial function with excessive vasoconstriction (low nitric oxide and prostaglandin bioavailability, increased thromboxane A2) thrombosis in situ (platelets depleted of serotonin)


  • smooth muscle cell proliferation


  • 2 hit hypothesis



    • Permissive genotype (i.e. Bone Morphogenic Protein [BMP] 2 mutation)


    • Second insult (i.e. thromboembolism, toxin, infection)


  • Histology



    • Predominantly small pulmonary arteries


    • Intimal hyperplasia, medial hypertrophy, adventitial proliferation, thrombosis in situ, inflammation


  • Genetics



    • 10 % of cases are familial


    • 2 known genetic mutations: BMP-2 and activin-like kinase 1

 

D.

World Health Organization (WHO) Group Classifications

1.

Pulmonary arterial hypertension (PAH3)

1.1.

Idiopathic (IPAH)

 

1.2.

Familial (FPAH)

 

1.3.

Associated with (APAH):

1.3.1.

Collagen vascular disease

 

1.3.2.

Congenital systemic-to-pulmonary shunts

 

1.3.3.

Portal hypertension

 

1.3.4.

HIV infection

 

1.3.5.

Drugs and toxins

 

1.3.6.

Other (thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders, splenectomy)

 

 

1.4.

Associated with significant venous or capillary involvement

1.4.1.

Pulmonary veno-occlusive disease (PVOD)

 

1.4.2.

Pulmonary capillary hemangiomatosis (PCH)

 

 

1.5.

Persistent pulmonary hypertension of the newborn

 

 

2.

Pulmonary hypertension with left heart disease

2.1.

Left-sided atrial or ventricular heart disease

 

2.2.

Left-sided valvular heart disease

 

 

3.

Pulmonary hypertension associated with lung diseases and/or hypoxemia

3.1.

Chronic obstructive pulmonary disease

 

3.2.

Interstitial lung disease

 

3.3.

Sleep-disordered breathing

 

3.4.

Alveolar hypoventilation disorders

 

3.5.

Chronic exposure to high altitude

 

3.6.

Developmental abnormalities

 

 

4.

Pulmonary hypertension due to chronic thrombotic and/or embolic disease (CTEPH)

4.1.

Thromboembolic obstruction of proximal pulmonary arteries

 

4.2.

Thromboembolic obstruction of distal pulmonary arteries

 

4.3.

Non-thrombotic pulmonary embolism (tumor, parasites, foreign material)

 

 

5.

Miscellaneous

5.1.

Sarcoidosis,

 

5.2.

Histiocytosis X

 

5.3.

Lymphangiomatosis

 

5.4.

Compression of pulmonary vessels

 

 

 


Diagnostic Work Up




A.

History



  • Symptoms: Dyspnea on exertion, fatigue, chest pain, syncope, palpitations, lower extremity edema (Table 22-1)


    Table 22-1
    Medical history associated with pulmonary hypertension



















































































    Group I—Pulmonary arterial hypertension
    Group II—PH with left heart involvement
    Group III—PH associated with lung disease and/or hypoxia
    Group IV—PH associated with to chronic thrombotic and/or embolic disease
    Group V—Miscellaneous

    Hemoglobinopathies
    Atrial or ventricular disease
    COPD
    Pulmonary embolism
    Sarcoidosis

    Sickle cell
    Systolic heart failure
    Interstitial lung disease
    Histiocytosis X

    β-thalessemia+/+

    Heart failure with preserved EF
    Obstructive sleep apnea
    Lymphangiomatosis

    Hereditary spherocytosis
    Constrictive or restrictive disease
    Compression of pulmonary vessels

    Family history of PAH (BMPR2 mutation)
    Dilated cardiomyopathy
    Adenopathy

    Connective tissue disease
    Valvular disease
    Tumor

    Limited cutaneous form of systemic sclerosis
    Mitral regurgitation
    Fibrosing mediastinitis

    SLE
    Mitral stenosis

    MCTD

    RA

    Liver disease/cirrhosis

    HIV

    Congenital heart disease with systemic shunt

    Drugs/toxin

    Fenfluramine

    Rapeseed oil

    Methamphetamine

    Cocaine

    Other

    Hereditary hemorrhagic telangiectasia

    Glycogen storage disease

    Gaucher disease

    Thyroid disorders

    Splenectomy


    +/+Standard nomenclature for homozygous gene

 

B.

Physical Exam (Table 22-2 [1])


Table 22-2
Signs of pulmonary hypertension [1]




































Early PH
Moderate to severe PH
Advanced PH with RV failure

Accentuated S2 (best heard at apex)
Holosystolic murmur that increases with inspiration
Right ventricular S3

Early systolic click
Increased jugular ‘v’ waves
Distension of jugular veins

Mid systolic ejection murmur
Pulsatile liver
Heptomegaly

Left parasternal lift
Diastolic murmur
Peripheral edema

Right ventricular S4
Hepatojugular reflux
Ascites

Increased jugular ‘a’ wave
  
Hypotension, decreased pulse pressure, cool extremities

 

C.

Diagnostic Studies



  • CXR



    • Right ventricular (RV) enlargement, peripheral hypovascularity, hilar enlargement


  • ECG



    • Right ventricular hypertrophy, right atrial enlargement, right axis deviation


  • Trans-thoracic echocardiography (Fig. 22-1)

    A306999_1_En_22_Fig1_HTML.gif


    Figure 22-1
    Echocardiographic differentiation of elevated RV systolic pressure


  • Further testing for diseases associated with pulmonary hypertension



    • ANA & other connective tissue disease serologies


    • Sleep study


    • Liver function tests


    • Pulmonary function tests


    • V/Q scan


    • HIV

 

D.

Right heart catheterization



  • Assess pulmonary vascular resistance to isolate pre-capillary and post-capillary contributions to pulmonary artery pressure


  • Pulmonary arterial hypertension is characterized by elevations in both mean pulmonary artery pressure (mPAP) and transpulmonary gradient (pre-capillary ­pulmonary hypertension) (Fig. 22-2) [35]

    A306999_1_En_22_Fig2_HTML.jpg


    Figure 22-2
    Diagnosing pulmonary venous/passive/post-­capillary hypertension vs pulmonary arterial/pre-capillary ­hypertension (Adapted from Chatterjeee and Lewis [35])




    • mPAP>25 mmHg


    • PCWP <15 mmHg


    • PVR  >  3 Woods units


  • Passive pulmonary hypertension (post-capillary pulmonary hypertension)



    • mPAP >25 mmHg


    • PCWP >15 mmHg


    • PVR <3 Woods Units


  • Mixed (or “Out of Proportion”) pulmonary hypertension



    • mPAP >25 mmHg


    • PCWP >15 mmHg


    • PVR >3 Woods Units


  • Pulmonary hypertension can be due to high pulmonary flow in the setting of high cardiac output


  • Assess for significant intra-cardiac shunt (O2 saturations from the superior vena cava, right ventricle, pulmonary artery, and femoral artery)


  • Assess for low cardiac output (<2.1 L/min/m2)


  • Assess for vasoreactivity to pulmonary vasodilators (Table 22-3)


    Table 22-3
    Agents for acute vasodilator testing [1]































     
    Nitric oxide
    Adenosine
    Epoprostenol

    Route of administration
    Inhaled
    IV infusion
    IV infusion

    Dose titration
    Nne
    50 mcg/kg/min every 2 min
    2 ng/kg/min every 10–15 min

    Dose range
    20–40 ppm for 5 min
    50–250 mcg/kg/min
    2–10 ng/kg/min

    Side effects
    ↑ Left heart filling pressures
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    Jul 13, 2016 | Posted by in CARDIOLOGY | Comments Off on Pulmonary Hypertension

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