Primary and Secondary Pulmonary Hypertension by cpf16541


									Primary and Secondary
Pulmonary Hypertension

Evaluation and Management

      Greg McKinnis, MD
        May 17, 2005
• Definitions
  – Classification issues
• Diagnostic Evaluation
  – Work-up
  – Determination of Severity
• Management
  – Pharmacologic advances
  – Surgical options
  – Transplantation
Normal Physiology

• Normal mPAP < 1/7th mAP

• High flow, Low resistance system

            80 x (mPAP– PCWP)
  – PVR = ___________________

• With exercise, only slight increase in
  mPAP, so signif. decreased PVR
Normal Physiology
• Decrease in PVR achieved with increase in
  x-sectional area of vascular bed by:
  – dilation of vessels perfused at rest
  – recruitment of new vessels

• HTN can result from decrease in area of
  any segment of pulmonary circulation
  – Arteries, arterioles, capillaries, venules, and
Definition of Pulmonary HTN
• Normal mPAP= 6-10mmHg
 HTN: mPAP >25mmHg at rest or >30mmHG
  after exercise

• PRIMARY Pulm Htn IF can rule out:
  –   Parenchymal lung dz
  –   Chronic thromboembolic dz
  –   Left-sided heart failure/valve dz
  –   Congenital heart dz
  –   Connective tissue dz (1/3 scleroderma; 1/2 CREST)
  –   HIV

• Typical onset in 4th decade
• Far more common in females
• Primary Pulmonary HTN
  – Can it be inherited?

• Typical onset in 4th decade
• Far more common in females
• Primary Pulmonary HTN
  – Can it be inherited?
  – YES -- 6-10% of cases
     • Inheritance is Autosomal Dominant
       – Incomplete penetrance
    • Often misdx’d as another
      cardiopulmonary dz

• Nonspecific and often reflect
  underlying dz (SPH):
  – Dyspnea on exertion
  – Fatigue, lethargy
  – Chest pain
  – Exertional syncope
  – Orthopnea/PND (think LV failure)

• Primary Pulmonary HTN
  – With susceptible genetic makeup, a final
    common response to inciting factors
  – Possible inciting factors
     • Endothelial damage from anorectics,
       cocaine, amphetamines, portal HTN,

• What mechanisms could result in
  decreased vascular caliber in PPH?

  Vascular remodeling:
         smooth muscle hypertrophy

• What mechanisms could result in decreased
  vascular caliber in PPH?


  Increased synthesis/activity of vasoconstrictors
  Decreased synthesis/activity of vasodilators

• Secondary Pulmonary HTN

   CONDITION                  MECHANISM
  Thromboembolic dz      large arterial impedance
  CTDz, PPHtn           small vessel impedance
  OSA, Chr. Mtn sickness hypoxic vasoconstriction
  Mitral stenosis, PVOD   venous drainage impedance
  COPD, ILD                  small vessel impedance +
                        hypoxic vasoconstriction
WHO Functional Classification of
 Pulmonary Hypertension

• Class I – No limitation in physical
• Class II –Dyspnea, fatigue, chest pain,
           or syncope with ordinary
• Class III – Dyspnea and/or fatigue with
            minimal activity. They are
            comfortable at rest.
• Class IV – Dyspnea and /or fatigue at
Diagnostic Work-Up

• R/O Secondary causes:
  – CXR, PFT’s, and possible HRCT
  – V/Q scan CT? MRA? PA-gram?
  – LFT’s, HIV
  – ANA, RF, Anti-Scl-70
  – PSG if symptoms of sleep apnea
Diagnostic Evaluation

• Echocardiogram—How specific?
  – OK--if measure TR jet velocity(39-86%)
  – PASP mean range of difference from PA
  – PADP rarely measured
  – Helpful in R/O: LV dysftn, Valve dz,
                  intracardiac shunt
  – Must confirm elevated PASP with RHC
Diagnostic Evaluation

• Cardiac catheterization
  – Left-sided cath:
     • Left atrial pressure, shunt
     • LV systolic and diastolic function

  – Right-sided cath:
     • PAP and CO
     • Assess reactivity of pulmonary
       vascular bed

• Conventional:
  – Diuretics: RV failure and fluid overload
  – Digoxin may improve RV function
  – Coumadin probably improves survival in
    all PAH (but especially CPTEPH)
  – Oxygen (improves survival but less
    effect on mPAP)
    Sheer stress
                        Shear stress
                                       High shear stress
Purinergis (e.g. ATP)
Vasoreactivity Testing

• IV epoprostenol, IV adenosine, or
  Inhaled NO

• Positive test:
  – Decrease in mPAP ≥10mmHg to ≤40mmHg
  – With increase or unchanged Cardiac Output
Treatment: Ca+ Channel Blockers

• If respond positively to vasodilator
  trial, CCB’s--improved survival
  – Nifedipine, Diltiazem, or Amlodipine

• Contraindicated in severe RVF and
  unstable patients

• Should not be initiated empirically
• Prostaglandin analogues
  – Epoprostenol(IV), Treprostenil(SQ), Iloprost(Inh),
    Beraprost(PO), Sitaxsentan(PO)

• Endothelin receptor antagonists
  – Bosentan(PO)

• Phosphodiesterase inhibitors (PDE-5)
  – Sildafenil for salvage therapy
  – May be useful in combination therapy with iNO, others
Treatment: Special Situations
• In addition to Primary Pulm HTN, trial of
  medical tx may be indicated for secondary
  Pulm HTN from:

  –   Scleroderma, other CTDz
  –   Portopulmonary HTN
  –   HIV
  –   Drugs and Toxins
  –   Thromboembolic disease
  –   Congenital heart disease
Treatment: Special Situations

• Forms of secondary pulmonary HTN
  in which vasodilator treatment has
  not been shown to be beneficial and
  may be harmful:

  – Left heart failure
  – Mitral valve disease
  – Chronic lung disease
Surgical Treatment

• Definitive:
  Pulmonary Thromboendarterectomy

• Salvage: Atrial Septostomy
  – As a bridge to transplantation

• Transplantation
  – For Class III or IV symptoms while assessing
    response to medical therapy
Pulmonary HTN-Summary
• Suspect if risk factors +/- exertional
  dyspnea or hypoxemia

• Echo adequate for screening and f/u

• Right heart cath needed for dx and
  accurate det’n of severity

• Class II/III/IV considered for tx
Pulmonary HTN-Summary

• R/O secondary pulmonary HTN
  – Tx underlying dz

• Primary pulmonary HTN may respond
  to host of new therapies
  – Secondary PAH studies underway

• Lung transplant for PPH (bilateral)
  – Refer when class III symptoms
The End
 Risk Groups for Screening

• Known genetic mutations predisposing
  to PH

• 1st degree relatives in familial PH

• Scleroderma spectrum of disease

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