Pulmonary Hypertension

• Pulmonary hypertension - Defined as an elevation in pulmonary arterial pressures (mean pulmonary arterial pressure >20mmHg)
• Types of Pulmonary Hypertension (Depending on etiology)

  →    Reactive type – increased pulmonary artery pressure (precapillary) – WHO Group 1, 3

  →    Passive type – increased pulmonary venous pressure (postcapillary) – WHO Group 2
• Pulmonary Pressure Measurement

  ·       Pulmonary pressure measurement is done by cardiac catheterization.

  ·       Cardiac catheterization is the gold standard and more accurate than 2D-echo.

  ·       Pulmonary measurement may also be done via 2D-echo or ultrasound but the results are only an estimate. Not accurate.

  ·       Swan-Ganz catheterization may also be utilized.
• Pulmonary Circulation: From the SVC,IVC and Coronary Sinus to RA then to RV then goes to the pulmonary trunk and arteries, then to the lungs from the lungs it goes back to via 4 pulmonary veins to the LA,LV and to the aorta
• precapillary – abnormality involves structures before blood goes to the lungs

  postcapillary- the abnormality is after the oxygenation of the blood. It involves the left side of the heart.
• Pulmonary vascular disease

  ·       Superimposed components:

  →    Vasoconstriction

  →    Nitric Oxide availability

  →    Desensitisation to NP-induced vasodilation

  →    Arteriolar remodeling

  →    Venous congestion

  →    Metabolic factors

  → Inflammatory cells
• When remodeling happens, thicker vessels, lumen becomes smaller; hence increase vascular resistance
• In reactive or precapillary type - there is an increase in flow to the pulmonary arteries to the lungs resulting to mean artery pressure increase.
• In passive or postcapillary type - there is an injury at the left side of the heart (commonly the left ventricle) resulting to increased left ventricular filling pressure (LV cannot handle increase in pressure). This increase in LV pressure is transmitted back to the left atrium then to the pulmonary veins resulting to pulmonary venous hypertension.
• Definition of Terms

  1. mPAP (mean pulmonary artery pressure)

  2. PCWP (pulmonary capillary wedge pressure)

  3. PVR (pulmonary vascular resistance)

  4. TPG (transpulmonic gradient)
• mPAP (mean pulmonary artery pressure)

  ·       Pressure in the Pulmonary Artery (precapillary)

  ·       NV <20 mmHg

  ·       Greater than the pulmonary capillary pressure (PCWP) to facilitate forward flow of blood into the lungs.

  ·       Measured using Swan Ganz Catheter
• PCWP (pulmonary capillary wedge pressure)

  ·       Pressure in the pulmonary capillary (postcapillary)

  ·       NV: <15 mmHg

  ·       Reflects the left ventricular filling pressure.

  ·       Less than the precapillary pressure (mPAP) to facilitate forward flow of blood into the lungs

  ·       Measured using the Swan Ganz catheter and /or echocardiography.
• PVR (pulmonary vascular resistance)

  ·       The resistance against blood flow from the pulmonary artery to the left atrium

  ·       Directly related to changes in pressure

  ·       Inversely related to pulmonary flow

  ·       Computed using right heart catheterization

  ·       NV: <3 Woods units
• Pulmonary Venous Hypertension VS Pulmonary Arterial Hypertension

  Hemodynamic Characteristics

  PH

  • mPAP > 20 mmHg

  Precapillary PH

  • PCWP </= 15 mmHg
  • PVR > 3 WU

  Postcapillary PH

  • PCWP > 15 mmHg
  • PVR </= 3 WU

  Mixed PH

  • PCWP > 15 mmHg
  • PVR > 3 WU
• Pulmonary Venous Hypertension VS Pulmonary Arterial Hypertension

  WHO Categories

  PH

  • All forms

  Precapillary PH

  • 1 -PAH
  • 3 - PAH 2 to Lung disease
  • 4 - CTEPH

  Postcapillary PH

  • 2 - Left heart failure (Systolic HF) - Passive PH

  Mixed PH

  • 2 - Left heart failure (Systolic and Diastolic HF)
• Underlying pathogenesis of pulmonary arterial hypertension: 

  →    Apoptosis resistance

  →    Cell proliferation

  →    Dysregulated metabolism

  →    Increased oxidant stress (pulmonary vascular cells & adventitial fibroblasts)
• ·       Pathological findings in pulmonary vasculature:

  →    Hypertrophic, fibrotic and plexogenic remodeling of distal (small) pulmonary arterioles

  ·       End-results:

  →    Decreased vascular compliance

  →    In situ thrombosis
• ·       Early Stages

  →    Vascular remodeling confined to the small distal pulmonary arteries

  ·       Advance Stages

  →    Intimal proliferation and pathologic remodeling progress

  →    Decreased compliance of the pulmonary vasculature

  →    Progressive increase in RV afterload/Total pulmonary vascular resistance

  →    Increase in RV work
• Pathobiology

  1. Pathologic changes to pulmonary arterial compliance
  2. Progressive increase in total pulmonary vascular resistance
  3. Rise in mean pulmonary arterial pressure
  4. 2 --> Progressive increase in RV afterload
  5. Increase in RV work
  6. Sustained increase in RV
  7. Shift in efficiency of RV systolic function
  8. Myocardial energy depletion
  9. RV pulmonary arterial uncoupling
• End Stage PAH

  1. Cardiac output decline
  2. Decrease in MPAP
  3. Extrapulmonary vascular manifestation
  4. Overactivation of neurohumoral signaling, renal failure, volitional muscle atrophy
• Myocardial energy depletion also depletes the energy reserved to maintain optimal blood perfusion through the alveolar-capillary interface for blood oxygenation
• Clinical presentation of pulmonary hypertension

  ·       Dyspnea

  ·       Edema

  ·       Chest Pain*

  ·       Presyncope*

  ·       Syncope*

  * = Advanced Diseases

  ·       Early phases of PH: Unrevealing PE

  ·       Progressive Disease

  →    RV Failure

  →    Elevated JVP

  →    Lower Extremity Edema

  →    Ascites

  →    Accentuated P2 (of the 2nd heart sound)

  →    Right-sided S3 or S4

  →    Holosystolic tricuspid regurgitation murmur
• Signs of diseases concurrent with PH

  ·       Chronic Lung Disease

  →    Clubbing

  ·       Scleroderma

  →    Sclerodactyly

  →    Telangiectasia

  ·       Heart Failure

  →    Crackles in left side heart failure

  →    Systemic Hypertension
• ·       Echo with bubble study- most important initial screening test

  ·       Important for determining specific causes:

  →    Valvular diseases

  →    Left Ventricular systolic and diastolic dysfunction

  →    Intracardiac shunts

  →    Other cardiac diseases

  ·       Echo findings in ALL forms of PH

  →    Hypertrophied and dilated RV

  Elevated estimated PAP
• Electrocardiogram

  ·       May show left-sided heart disease (underlying cause)

  →    Left ventricular hypertrophy

  →    Left atrial enlargement

  ·       Signs of right-sided heart disease (more advanced disease)

  →    Right axis deviation

  →    RV hypertrophy

  →    Signs of RV strain (CTEPH)

  ·       Arrhythmias secondary to pulmonary disease or left heart disease

  →    Frequent arterial premature contractions

  →    Multifocal atrial tachycardia

  Atrial fibrillation
• ECHOCARDIOGRAM: Dilated right—sided chambers Flattening of the interventricular septum (RV pressure overload)
• Chest Radiograph

  ·       Enlargement of the central pulmonary arteries

  ·       Vascular pruning

  ·       Cardiomegaly
• Cardiopulmonary Exercise Test (CPET)

  ·       Identification of true physiologic limitation

  ·       Differentiate between cardiac and pulmonary causes of dyspnea

  ·       If normal = No indication for RHC
• Invasive Hemodynamic Monitoring

  ·       Gold standard for diagnosis and assessment of disease severity

  ·       Right heart catheterization (RHC)- for definitive diagnosis

  →    Unexplained dyspnea or hypoxemia

  →    Normal Echocardiogram

  ·       RHC with pulmonary vasodilator testing

  →    Gold standard both to establish diagnosis of PH to guide selection of appropriate medical therapy

  →    RHC with addition of vasodilator substances/hyperoxygenation of the patient, to see if there’s an improvement in the PH (dropping of pressure with vasodilators)
• RHC with Pulmonary vasodilator testing

  ·       Vasodilators

  →    Inhaled Nitric Oxide

  →    Inhaled Epoprostenol

  ·       Interpretation

  →    Decrease in mPAP >10mmHg to an absolute level <40mmHg without a decrease in cardiac output

  →    POSITIVE PULMONARY VASODILATOR RESPONSE

  →    Consider long-term treatment with Calcium Channel Blockers CCBs
• High-Resolution Computed Tomography

  ·       Enlarged pulmonary arteries

  ·       Peripheral pruning of small vessels

  ·       Enlarged right ventricle and atrium

  ·       Signs of venous congestion (PULMONARY VENOUS DISEASE)

  →    Centrilobular ground glass infiltrates

  →    Thickened septal lines

  ·       Pulmonary comorbidities

  →    Interstitial lung disease

  Emphysema
• Chest CT Angiogram

  ·       Evaluation of acute thromboembolic disease (excellent sensitivity and specificity)

  ·       Injection of dye to visualize vasculature

  ·       Controversial role in the diagnosis of Chronic Thromboembolic PH (CTEPH)
• Ventilation-Perfusion (V/Q) Scanning

  ·       Useful screening tool (high sensitivity) for evaluation of thromboembolic disease

  ·       Has a role in determining which patients qualify for surgical intervention

  ·       Can rule out CTEPH if NEGATIVE
• pulmonary function tests

  ·       Classic finding in PAH:

  →    Isolated reduction in diffusing capacity of the lungs for carbon monoxide (DLCO)

  ·       Restrictive or Obstructive Lung Diseases
• 6-Minute walk test

  ·       Evaluation of the degree of exertional hypoxemia and limitation

  ·       Monitoring tool for progression and response to therapy
• sub-maximal and maximal exercise testing

  ·       Screening and characterization of the PH

  ·       Provides a more objective measure of breathing efficiency (VE/VCO2 slope)
• sleep studies

  ·       Diagnosis of sleep-disordered breathing as an important cause of mild PH

  ·       Generally necessary only when indicated by the patient’s history

  ·       Can be done for px with short neck and if px is snoring
• nocturnal oximetry screening

  ·       A must for all patients regardless of presence or absence of classic symptoms of obstructive sleep apnea or obesity hypoventilation syndrome

  ·       Nocturnal desaturation-present even in the absence of sleep-disordered breathing
• pulmonary hypertension classification

  ·       Group I: Pulmonary Arterial Hypertension

  ·       Group II: Pulmonary Hypertension Associated with Left Heart Disease

  ·       Group III: Pulmonary Hypertension Associated with Lung Disease

  ·       Group IV: Pulmonary Hypertension Associated with Thromboembolic Disease

  ·       Group V: Other Disorders Affecting the Pulmonary Vasculature
• WHO Group I: pulmonary arterial hypertension

  ·       Includes a group of diseases that result in pulmonary arterial precapillary remodeling

  →    Intimal fibrosis

  →    Increased medial thickness

  →    Pulmonary arteriolar occlusion

  →    Plexiform lesions