Pulmonary Hypertension

PH Basics - Pressure Cooker Lungs

• Defined by mean pulmonary arterial pressure ($mPAP$).

  ⭐ The 2022 ESC/ERS guidelines redefine pulmonary hypertension as $mPAP$ > 20 mmHg at rest.

• Normal $mPAP$: $14 \pm 3$ mmHg.
• Pathophysiology: ↑ Pulmonary Vascular Resistance (PVR) leads to Right Ventricular (RV) pressure overload ("pressure cooker" effect), causing potential RV failure.
• WHO Clinical Classification (5 Groups):
  • Group 1: PAH (Pulmonary Arterial Hypertension)
  • Group 2: PH due to Left Heart Disease
  • Group 3: PH due to Lung Diseases/Hypoxia
  • Group 4: CTEPH (Chronic Thromboembolic PH)
  • Group 5: PH with unclear/multifactorial mechanisms

Vessel Chaos - Why Lungs Squeeze

• Primary Insults:
  • Endothelial dysfunction: ↓NO, ↓Prostacyclin; ↑Endothelin-1.
  • Vascular Smooth Muscle (VSM) proliferation & hypertrophy.
  • Inflammation & immune dysregulation.
  • Abnormal coagulation (in-situ thrombosis).
• Structural Changes (Remodeling):
  • Medial hypertrophy, intimal proliferation, adventitial thickening.
  • Plexiform lesions (pathognomonic for severe PAH).
• Genetic Predisposition:
  • BMPR2 gene mutations (esp. in Heritable PAH).
• Hemodynamic Consequence: ↑PVR → ↑PAP → RV overload → RV failure.

⭐ Key pathogenic pathways include endothelial dysfunction (↓NO, ↓prostacyclin, ↑endothelin-1), vascular smooth muscle proliferation, and in-situ thrombosis. BMPR2 mutations are common in heritable PAH.

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Spotting PH - Breathless Clues

• Symptoms:
  • Progressive exertional dyspnea (key)
  • Fatigue, weakness
  • Angina-like pain, exertional syncope
  • Peripheral edema, ascites (RHF signs)
• Signs:
  • Loud, palpable P2
  • RV heave (parasternal lift)
  • ↑ JVP (prominent 'a'/'cv' waves)
  • Murmurs: TR (LLSB, ↑ insp.), Graham Steell (PR, LUSB, ↑ insp.)
• Initial Workup:

  • ECG: RVH (RAD, RBBB, P pulmonale), RV strain

  • CXR: Enlarged central PAs, RV prominence, clear lungs

  • Echocardiography (TTE):

    • Estimates RVSP (TR jet > 2.8 m/s suggests PH)
    • Formula: RVSP $\approx 4 \times (TRV_{max})^2$ + RAP
    • Assesses RV size/function (TAPSE < 17mm, S' < 9.5 cm/s), PA dilation

  • 6MWD: Functional status (< 300m poor prognosis)

⭐ RHC: gold standard. Confirms mPAP > 20 mmHg. Pre-capillary PH: PAWP ≤ 15 mmHg & PVR > 2 Wood Units.

Easing Pressure - Treatment Tactics

• General: Diuretics (RHF), O2 (PaO2 < 60 mmHg), anticoagulation (PAH, CTEPH), exercise, vaccines.
• PAH (WHO Group 1):
  • RHC + Acute Vasoreactivity Test (AVT).

    ⭐ Acute vasoreactivity testing during RHC is crucial for WHO Group 1 PAH; positive responders (mPAP drop ≥10 mmHg to reach mPAP ≤40 mmHg, with ↑/unchanged CO) may benefit from CCBs.

  • AVT (+): High-dose CCBs (Nifedipine, Diltiazem).
  • AVT (-) / CCB failure: Risk-stratified targeted therapies.
    • 📌 ERAs (BAM!): Bosentan, Ambrisentan, Macitentan.
    • 📌 PDE-5i (Fill!): Sildenafil, Tadalafil.
    • 📌 Prostacyclin pathway (EITS!): Epoprostenol, Iloprost, Treprostinil, Selexipag.
    • sGC stimulator: Riociguat.
  • Initial/sequential combination therapy common. Lung transplant if refractory.
• Other PH Groups: Treat underlying cause.
  • Group 2: LHD management.
  • Group 3: Lung disease Rx, O2.
  • Group 4 (CTEPH): Anticoagulation; PEA/BPA; Riociguat.
  • Group 5: Address specific etiology.

High‑Yield Points - ⚡ Biggest Takeaways

• Pulmonary Hypertension (PH): Defined by mPAP >20 mmHg at rest, confirmed by RHC.
• Group 1 (PAH) treatment involves targeted therapies: prostanoids, ERAs, PDE5 inhibitors.
• Most common overall PH cause: Left heart disease (WHO Group 2).
• Group 3 PH: Caused by lung diseases or chronic hypoxia (e.g., COPD, ILD).
• Gold Standard Diagnosis: Right Heart Catheterization (RHC) for definitive assessment.
• Key ECG findings: Right Ventricular Hypertrophy (RVH), P pulmonale, right axis deviation.
• Auscultation: A loud P2 heart sound is a characteristic clinical sign.