L21 Pulmonary Hypertension

• 
• As resistance goes up:
• 1. Pressure increases (pulmonary HTN)
• 2. CO decreases
• *usually both

Mean pulmonary arterial pressure > 25mmHg

• Often estimated by Echo:
• -measures tricuspid regurgitation jet (present in most ppl)
• -systolic PAP = (4V²) + CVP

• Measure with Right Heart Cath:
• -need accurate number

• -female predominance (especially idiopathic)
• -may develop at any age (related to etiology)

• Symptoms:
• -SOB
• -hypoxemia
• -swollen feet and ankles
• -chest pain
• -syncope
• -cyanosis

• Physical Exam Findings:
• -hypoxemia (usually later in course)
• -elevated JVP
• -enhanced/delayed P2 (pathologic splitting)
• -Right sided S3 or S4 gallop
• -pulmonic bruit (CTPH)
• -peripheral edema
• -possibly clubbing

• Imaging:
• 
• -enlarged cardiac silhouette (esp RA)
• -enlarged R pulmonary artery

• 1. PAH
• -idiopathic
• -Heritable
• -Drug induced

1'. Pulmonary veno occlusive disease/Pulmonary capillary hemangiomatosis

2. Pulmonary HTN due to left heart disease

• 3. Pulmonary HTN due to lung diseases/hypoxia
• -COPD
• -interstitial lung disease
• -sleep-disordered breathing
• -high altitude

4. Chronic thromboembolic pulmonary hypertension

• 5. PH with unclear or multifactorial mechanisms
• -hematologic disorders
• -systemic disorders
• -metabolic disorders
• -other

• -young/middle aged women
• -many have had sx for years (asthma, syncope)
• -no identifiable specific causes (diet drugs, autoimmune disease, PEs, LVF)

• Imaging:
• 
• -R heart hypertrophy
• -lack of anterior clear space in front of heart

• 
• -chronic pericardial effusion

• 
• -reflux of contrast into liver due to tricuspid regurgitation/RHF

• Bone Morphogenetic Protein Receptor 2 (BMPR2)
• -70% of familial cases
• -20% of idiopathic

• Activin-like kinase type 1 (ALK1)
• -found in HHT (hereditary hemorrhagic telangectasia)

• Endoglin (ENG)
• -also found in HHT

• 1. Anorexic Agents
• -fen-phen

2. Methamphetamine

3. Cocaine

4. SSRIs? MDMA?

• -attributed to viral effect itself
• -may be more closely related to other lifestyle choices (amphetamines)

• -primarily seen with systemic sclerosis (scleroderma)
• -may be severe and rapidly progressive
• -patients benefit from immunosuppression (cyclophosphamide, prednisone)

• -PAH associated with elevated portal venous pressures
• -typically due to cirrhosis
• -high mortality if untreated (still poor with tx)
• -usually treatable with PAH meds
• -high risk of mortality with liver transplant

NOT THE SAME AS HEPATOPULMONARY SYNDROME

1. Congenital abnormalities (VSD, ASD, PDA)

• 2. Eisenmenger's syndrome
• -L to R shunt becomes R to L shunt

Patients are often very sick

• -HTN on arterial side secondary to HTN on venous side
• ** meds to tx PAH usually make them worse!

• Imaging:
• 
• -nodules
• -well demarcated lymphatics within pulmonary parenchyma
• -lymph adenopathy

• 1. LVF (most common cause of elevated pulmonary artery pressure)
• 2. Mitral Valve stenosis
• 3. Mitral Regurg
• 4. Restrictive cardiomyopathy
• 5. Aortic valve stenosis

NOT cor pulmonale (lungs are not the initial insult)

• Do not typically improve with standard PAH therapy
• -increased blood flow into LA overloads the L heart --> pulmonary edema, effusions, respiratory failure

• 
• -increased LA stretch triggers vasoconstriction of pulmonary arterioles

-protects capillaries from high pressure

-can be overwhelmed (pulmonary edema, capillary rupture/hemorrhage, pleural effusions)

-P in PA increases much more than LA pressure

• Causes:
• -COPD
• -Interstitial lung disease
• -Sleep-disordered breathing
• -Chronic high altitude exposure
• -Developmental abnormalities

• Chronic Hypoxemia:
• -leads to hypoxic vasoconstriction (may develop SM proliferative changes)

• Parenchymal Destruction:
• -lose pulmonary vasculature --> same amount of blood/fewer vessels --> increased resistance

• Accumulate multiple emboli over time
• -can result from recognized acute PE (estimated in 2-4% of PE)

• May have a genetic predisposition
• -mutations in fibrinogen

• Treatment:
• -may respond to traditional PAH meds
• -Surgical resection the mainstay of therapy (Pulmonary thromboendarterectomy)

• 1. Hematologic disorders
• -myeloproliferative disorders
• -splenectomy

• 2. Systemic disorders
• -sarcoidosis
• -pulmonary Langerhans cell histiocytosis
• -NF
• -vasculitis

• 3. Metabolic disorders
• -glucogen storage disease
• -gaucher disease
• -thyroid disorders

• 4. Other
• -tumor obstruction
• -fibrosing mediastinitis
• -chronic renal failure

• Treatment:
• -very difficult to treat
• -not usually responsive to PAH meds
• -address underlying cause if able
• -manage symptomatically

-SM hypertrophy of small arteries and arterioles

-intimal hyperplasia (luminal obliteration)

-plexiform (weblike) changes of small arterioles

-RV concentric hypertrophy, dilation

• -Untreated 50% survival at 2 years
• -Still poor even with therapy

• -Frequent hospitalizations
• -repeated surgical procedures (catheter placement)
• -electrolyte abnormalities
• -renal dysfunction
• -bloodstream infections (catheters)
• -liver dysfunction
• -limited exercise tolerance

I: no functional limitations

II: sx with moderate exertion

III: sx with mild exertion

IV: sx at rest

• 1. CCB
• -verapamil
• -diltiazem

2. PDE5 inhibitors

3. Endothelin receptor antagonists

4. Prostacyclins

• -verapamil
• -diltiazem

-ineffective in most patients (class I)

-inhaled NO testing during R heart cath to test for vasoresponsiveness

-patients typically graduate to more effective therapies

• -sildenafil
• -tadalafil

-good oral therapy for mild disease (I or II)

-typically well tolerated

-not used first line for class III to IV

-often started by non-specialists --> may delay necessary evaluation and tx

• -bosentan
• -ambrisentan

• -more potent than other oral agents
• -can be used in mild-moderate (class II-III)

-must monitor hepatic function but typically well tolerated

-HIGHLY TERATOGENIC

• -Epoprostenol
• -Treprostinil (inhaled)
• -Iloprost (inhaled)

• -most potent class of medications (Class III-IV)
• -prolong survival and improve quality of life

-difficult administration: continuous IV infusion (need indwelling catheter)

-drug delivery associated complications (infections, surgery)

• -remember Ohm's law!
• -Drop in PA pressure may be due to decreased PVR OR decreased cardiac output!
• -patients may actually be getting WORSE!

-reserved for severe progression despite medical therapy

-typically bilateral (now starting to do more unilateral)

• High risk associated with surgery/anesthesia
• -increased intrathoracic pressure from mechanical ventilator leads to increased RV pressure --> right heart failure