Idiopathic Pulmonary Arterial Hypertension (IPAH)

Epidemiology

  • Prevalence: at autopsy, PPH is found in 1% of Cor Pulmonale cases
  • Predisposing Factors: female sex (F:M ratio is 1.7:1 in younger cases/ ratio 1:1 in older pts.)
    • Mean Age at Presentation: 36 y/o (range 1-81 y/o)
    • Autosomal Dominant (with variable expression): 7% of cases
    • OCP Use:
    • Migraine
    • Variant angina

Physiology

  • Defined as persistent resting mean PA >25 mmHg (or mean PA >30 mmHg during exercise)
  • Increased resistance to pulmonary blood flow (initially responsive to vasodilators but later fixed) with eventual right-sided CHF (with decreased CO)

Pathologic Subtypes

  • Plexogenic pulmonary arteriopathy (30-60% of cases/ more common type in younger fe-males/ also seen in CHD, cirrhosis, collagen vascular disease/ Aminorex): medial hypertrophy, concentric laminar intimal fibrosis, plexiform lesions
  • Thrombotic pulmonary arteriopathy (40-50% of cases/ M:F ratio: 1:1/ also seen in ASD): eccentric intimal fibrosis, medial hypertrophy, fibroelastic intimal pads in arteries and arterioles, old recanalized thrombi

Diagnosis

  • ABG: hypocapnea/hypoxemia with increased A-a gradient (due to decreased CO, V/Q mismatch/intrapulmonary shunt/occasionally due to opening of PFO with intracardiac shunt)
  • PFT’s: usually normal, but mild restriction is occasionally seen/ decreased DLCO (usual)
  • Exercise test: exercise desaturation
    • VD/VT ratio: remains the same or increases
  • Lung Biopsy: not usually necessary
  • CXR: enlarged PA’s with clear lung fields/ cardiomegaly
  • V/Q scan:
    • Normal pattern (common in plexogenic subtype): presence of normal V/Q in presence of severe pulmonary HTN strongly suggests PPH
    • Mottled pattern (common in thrombotic subtype): subsegmental areas of decreased perfusion
      • Presence of lobar or segmental defects suggests CTPEH instead
  • Pulmonary Angiogram: “pruning” of peripheral vessels
    • Usually not necessary in presence of diagnostic V/Q pattern
  • ESR:
  • Serology
    • ANA: positive (>1:80 titer) in up to 30-40% of cases (most have speckled pattern)
    • Antiphospholipid Ab’s: may be seen in some cases
  • CBC: polycythemia (may be seen)/ MAHA (seen in a few cases, due to plexiform lesions)
  • EKG
    • RAD with RVH (R in V1 >5, etc.)
    • RAE
  • Echo: RVE with decreased LV cavity size/ abnormal septum/ dependence on atrial systole for RV filling
    • TR (by Doppler): jet peak vel squared x 4 + CVP estimates PA-SYS pressure
    • Bubble study: excludes intracardiac shunt (VSD/ ASD/ etc.)/ PFO seen in 20% of PPH cases
  • Swan
    • RA and RV-SYS: elevated
    • PA-Mean: elevated >25 mm Hg at rest or >30 mm Hg during exercise
    • PA-SaO2: lack of “step-up” excludes intracardiac shunt
    • PCWP: normal (due to normal LA, LV-EDP)
    • CO: normal-decreased at rest (does not rise appropriately with exercise)
    • SVR: normal
    • PVR: elevated
  • Cardiac Cath: PFO may occur due to pulmonary HTN, but L-to-R shunt suggests congenital defect
  • Angioscopy: may be necessary to rule out CTEPH in some cases

Clinical

  • Dyspnea (95%): insidious (no correlation with degree of pulmonary HTN): average duration from onset to diagnosis is 2.5 years
  • Symptoms of right-sided CHF: ascites,etc.
  • Hemoptysis (due to ruptured vessels)
  • Fatigue
  • Angina (due to RV ischemia, PA stretch)
  • Syncope (decreased CO)
  • Raynaud’s phenomenon (10-30%):
  • Hoarseness (PA impingement on recurrent laryngeal)
  • Signs of right-sided CHF: peripheral edema, right-sided S3 and S4
  • Signs of pulmonary HTN: split S2, accentuated P2/ RV heave, etc.
  • Low pulse pressure
  • Peripheral cyanosis
  • Absence of clubbing
  • Sudden death (occurs late)
  • Central PA Thrombi: may occur (probably later) secondary to low flow state with in situ thrombosis (Circ, 1995)
    • The removal of these by PTE does not treat underlying PPH and these patients do not come off CPB

Treatment

  • Avoidance of the following:
    • Exercise: increases PA pressures (and workload on RV
    • Hypoxia:
    • Smoking:
    • NSAIDS: due to effect of prostaglandins
    • Pregnancy:
    • PGF2a: increases PVR
    • Barbiturates: decrease CO
  • Oxygen: useful to ameliorate hypoxia
  • Diuretics: decrease RV preload
  • Pulmonary Vasodilator Trial (with Swan in place to avoid decrease in CO and BP):
    • Vasodilator Response (decrease in mean PA >10 to mean PA <40 with stable-increased CO):
      • Calcium-Channel Blockers (Nifedipine/Diltiazem):
    • No Vasodilator Response:
      • Avoid Calcium-Channel Blockers (due to risk of hypotension, acute right-sided heart failure, and death)
      • Prostacyclin (Flolan): indicated for class III patients and is the drug of choice for class IV patients
        • Improves exercise capacity, QOL, hemodynamics, and survival
      • Bosentan (Endothelin-1 Receptor Antagonist): indicated for NYHA III patients
        • Improves exercise tolerance, hemodynamics, functional class (over 1 year)
        • Monitor qmonthly LFT s and avoid pregnancy (teratogenic)
      • Sildenafil (): may be used
  • Anticoagulation: documented (retrospectively only) to prolong survival
    • Does not affect disease process
  • Heart-Lung Transplant: for patients with <1 year survival

Prognosis

  • Mean survival is 2-3 years (range: 0.5-3.5 years)
  • RA mean>15, CI <2, NYHA 3-4, presence of Raynaud’s, elev mean PA, decreased DLCO, more elevated JVP: poorer prognosis (prognosis not correlated with pO2)

References

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