# Clinical Cases: Pulmonary Vascular Disease

## Case 1: Massive Pulmonary Embolism - Hemodynamic Instability

### Clinical Image
![Saddle Pulmonary Embolism](case_01_image.jpg)
*Source: [Wikimedia Commons - CT pulmonary angiography PE](https://commons.wikimedia.org/wiki/File:Saddle_PE.png) - CC BY-SA 3.0*

### Patient Presentation
A 58-year-old man collapses at home and is brought to the emergency department by ambulance. His wife reports he had been complaining of increasing shortness of breath over the past 3 days and had leg swelling for 2 weeks. He had surgery for a hip fracture 3 weeks ago. In the ambulance, he developed a syncopal episode with transient loss of consciousness.

### Demographics
- Age: 58 years
- Sex: Male
- Past Medical History: Hypertension, hip fracture (surgery 3 weeks ago), limited mobility during recovery
- Medications: Lisinopril, aspirin (DVT prophylaxis stopped after discharge)
- Social History: Former smoker

### Chief Complaint
Sudden collapse with syncope, progressive dyspnea, and leg swelling

### Physical Examination
- Blood pressure: 78/52 mmHg (hypotensive)
- Heart rate: 124 bpm
- Respiratory rate: 32/min
- Oxygen saturation: 82% on room air, 88% on 15L non-rebreather
- Temperature: 37.2°C
- General: Diaphoretic, anxious, cyanotic
- Neck: Markedly elevated JVP
- Cardiovascular: Tachycardic, loud P2, right-sided S3
- Respiratory: Clear to auscultation
- Extremities: Left leg swollen (3 cm larger than right), tender, erythematous

### Workup
- ECG: Sinus tachycardia, S1Q3T3 pattern, right bundle branch block, T wave inversions V1-V4
- Troponin: 0.45 ng/mL (elevated)
- BNP: 1,850 pg/mL (markedly elevated)
- D-dimer: >5,000 ng/mL
- ABG: pH 7.28, PaCO2 28 mmHg, PaO2 52 mmHg (on 15L O2), lactate 5.8 mmol/L
- Bedside echocardiography: Severely dilated RV, RV free wall hypokinesis with apical sparing (McConnell sign), D-shaped septum, tricuspid regurgitation
- CT pulmonary angiography: Saddle embolus at main pulmonary artery bifurcation with extension into bilateral main and lobar pulmonary arteries
- Lower extremity duplex: Extensive DVT in left femoral and popliteal veins

### Diagnosis
Massive (High-Risk) Pulmonary Embolism with Hemodynamic Collapse

### Treatment
1. **Immediate anticoagulation**: Unfractionated heparin bolus and infusion
2. **Systemic thrombolysis**: Alteplase 100 mg IV over 2 hours
   - Indicated for massive PE with hemodynamic instability
   - No absolute contraindications in this patient
3. Vasopressor support (norepinephrine) to maintain MAP
4. Avoid aggressive fluid resuscitation (already RV overload)
5. Consider surgical embolectomy or catheter-directed therapy if thrombolysis fails
6. ICU monitoring
7. Transition to long-term anticoagulation (warfarin or DOAC) for minimum 3 months (provoked by surgery/immobility)

### Physiological Principles Demonstrated
- **Hemodynamic impact of massive PE**: Acute obstruction of >50% of the pulmonary vascular bed causes acute RV pressure overload. The thin-walled RV cannot generate pressures >50-60 mmHg acutely, leading to RV failure.
- **RV-LV interdependence**: RV dilation causes the interventricular septum to shift leftward (D-sign), impairing LV filling and reducing cardiac output.
- **McConnell sign specificity**: RV free wall hypokinesis with apical sparing is specific for acute PE (apex is tethered to the LV).
- **V/Q mismatch and dead space**: PE creates regions of ventilation without perfusion (dead space), causing hypoxemia and hypocapnia from compensatory hyperventilation.

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## Case 2: Pulmonary Arterial Hypertension - Progressive Dyspnea

### Clinical Image
![Pulmonary Hypertension Echo](case_01_image.png)
*Source: [Wikimedia Commons - Pulmonary hypertension](https://commons.wikimedia.org/wiki/File:Pulmonary_hypertension.svg) - CC BY-SA 3.0*

### Patient Presentation
A 35-year-old woman presents with progressive exertional dyspnea over the past year. She initially noticed breathlessness when climbing stairs, but now she becomes short of breath walking short distances. She also reports occasional chest discomfort with exertion and has had two episodes of near-syncope during physical activity in the past month. She denies any prior lung or heart disease.

### Demographics
- Age: 35 years
- Sex: Female
- Past Medical History: Raynaud phenomenon, positive ANA (followed but no definitive diagnosis)
- Medications: None
- Family History: Sister with "lupus"

### Chief Complaint
Progressive exertional dyspnea, near-syncope with exertion

### Physical Examination
- Blood pressure: 108/72 mmHg
- Heart rate: 92 bpm at rest
- Respiratory rate: 18/min at rest
- Oxygen saturation: 94% on room air (drops to 86% with ambulation)
- General: Thin, appears fatigued
- Neck: Elevated JVP with prominent a-wave
- Cardiovascular: RV heave, loud P2 (palpable), grade 3/6 holosystolic murmur at left lower sternal border (TR), right-sided S4
- Respiratory: Clear
- Extremities: Mild peripheral edema, nail fold capillary changes consistent with scleroderma spectrum

### Workup
- ECG: Right axis deviation, RV hypertrophy, R > S in V1
- Chest X-ray: Enlarged main and hilar pulmonary arteries, clear lung fields, RV enlargement
- BNP: 420 pg/mL
- ANA: Positive (1:640, nucleolar pattern)
- Anti-Scl-70: Positive
- PFTs: Mildly reduced DLCO (52% predicted), normal spirometry
- V/Q scan: Normal (excludes CTEPH)
- Echocardiography: Estimated RVSP 75 mmHg, RV dilation and hypertrophy, flattened interventricular septum
- **Right heart catheterization**:
  - Mean PAP: 52 mmHg (PH confirmed)
  - PCWP: 10 mmHg (pre-capillary PH)
  - PVR: 12 Wood units (elevated)
  - Cardiac output: 3.8 L/min (reduced)
  - Acute vasodilator challenge: Negative (no acute responders)

### Diagnosis
WHO Group 1 Pulmonary Arterial Hypertension associated with Systemic Sclerosis

### Treatment
1. Risk stratification: Intermediate-high risk (WHO FC III, elevated BNP, near-syncope)
2. **Combination PAH therapy** (initial triple therapy considered for high-risk):
   - Endothelin receptor antagonist (ambrisentan or macitentan)
   - PDE-5 inhibitor (tadalafil) or sGC stimulator (riociguat)
   - Consider prostacyclin analog if needed
3. Diuretics for fluid management
4. Supplemental oxygen with exercise
5. Anticoagulation (controversial; often used in IPAH, less clear in CTD-PAH)
6. **Contraception counseling** (pregnancy contraindicated - 30-50% mortality)
7. Referral to expert PAH center
8. Lung transplant evaluation if disease progression

### Physiological Principles Demonstrated
- **PAH pathophysiology**: Pulmonary vascular remodeling (intimal proliferation, medial hypertrophy, in situ thrombosis) increases pulmonary vascular resistance, leading to RV pressure overload and eventual RV failure.
- **CTD-PAH association**: Systemic sclerosis has the highest prevalence of PAH among connective tissue diseases (~15%), particularly in those with limited cutaneous disease.
- **Exertional syncope significance**: Indicates inability to augment cardiac output with exercise due to fixed pulmonary vascular resistance - a poor prognostic sign.
- **Right heart catheterization importance**: Gold standard for diagnosis; distinguishes pre-capillary (PAH) from post-capillary (left heart disease) PH based on PCWP.

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## Case 3: Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

### Clinical Image
![CTEPH V/Q Scan](case_01_image.jpg)
*Source: [Radiopaedia - CTEPH](https://radiopaedia.org/articles/chronic-thromboembolic-pulmonary-hypertension) - Educational use*

### Patient Presentation
A 62-year-old man is referred to a pulmonary hypertension center with progressive dyspnea over 2 years. He had a documented pulmonary embolism 4 years ago following a long flight, for which he received 6 months of anticoagulation. He improved initially but has had slowly worsening exercise tolerance for the past 2 years. His primary care physician recently detected elevated pulmonary pressures on echocardiography.

### Demographics
- Age: 62 years
- Sex: Male
- Past Medical History: Pulmonary embolism 4 years ago, obesity, former smoker
- Medications: None currently (completed anticoagulation 3.5 years ago)
- Social History: Retired, sedentary lifestyle

### Chief Complaint
Progressive exertional dyspnea for 2 years, worsening despite initial recovery from PE

### Physical Examination
- Blood pressure: 132/78 mmHg
- Heart rate: 88 bpm
- Respiratory rate: 20/min
- Oxygen saturation: 92% on room air
- General: Obese, appears comfortable at rest
- Neck: Elevated JVP
- Cardiovascular: Loud P2, RV heave, holosystolic murmur at left lower sternal border
- Respiratory: Clear
- Extremities: Moderate bilateral lower extremity edema

### Workup
- Echocardiography: Estimated RVSP 68 mmHg, RV dilation, TR moderate
- BNP: 380 pg/mL
- **V/Q scan**: Multiple large, bilateral segmental and subsegmental mismatched perfusion defects (high probability)
- CT pulmonary angiography: Chronic organized thrombus with webs and bands in lobar and segmental arteries, mosaic attenuation in lung parenchyma
- Pulmonary angiography: Confirms chronic thromboembolic disease, surgically accessible
- **Right heart catheterization**:
  - Mean PAP: 48 mmHg
  - PCWP: 12 mmHg
  - PVR: 8 Wood units

### Diagnosis
Chronic Thromboembolic Pulmonary Hypertension (WHO Group 4)

### Treatment
1. **Lifelong anticoagulation** (regardless of surgical intervention)
2. **Pulmonary thromboendarterectomy (PTE)** - potentially curative:
   - Surgery to remove organized, fibrotic thrombus from pulmonary arteries
   - Performed at specialized centers on cardiopulmonary bypass with deep hypothermic circulatory arrest
   - Cure rate >85% in appropriately selected patients
3. If inoperable or residual PH post-surgery:
   - **Riociguat** (FDA-approved for inoperable/persistent CTEPH)
   - **Balloon pulmonary angioplasty** (BPA) for distal disease
4. Diuretics and oxygen as needed
5. IVC filter not routinely indicated if anticoagulated

### Physiological Principles Demonstrated
- **CTEPH pathogenesis**: 2-4% of acute PE patients develop CTEPH when thrombus does not resolve but organizes into fibrous tissue, causing mechanical obstruction and secondary arteriopathy.
- **V/Q scan sensitivity**: V/Q scan is more sensitive than CTPA for detecting chronic organized thrombus and is essential in CTEPH workup; normal V/Q effectively excludes CTEPH.
- **Surgical cure potential**: Unlike PAH, CTEPH is potentially curable because the obstruction is mechanical and can be surgically removed if disease is proximal.
- **Progression despite initial PE treatment**: CTEPH can develop even after "adequate" anticoagulation; ongoing symptoms after PE should prompt evaluation.