Pulmonary Aterial Hypertension Flashcards
Cardiac Anatomy
Normally pressures higher on left side of heart, goes all throughout body; right side just goes to lungs, lower pressure
PAH we’re focused on pulmonary artery –> have elevated pressures in this vessel and the right side of the heart not equipped to pump high pressures
Pulmonary Hypertension
- Pulmonary hypertension is higher than normal blood pressure in the arteries that carry blood away from the heart into the lungs
- Pulmonary Hypertension (PH)
– Mean pulmonary artery pressure (MPAP) ≥ 20 mmHg at rest
– More common - Pulmonary Arterial Hypertension(PAH)
– Progressive disease involving endothelial lung dysfunction –> elevated pulmonary
arterial pressure and pulmonary vascular resistance
– Rare
WHO Classification
Group 1: pulmonary arterial hypertension
causes:
- Unknown (idiopathic) - more common in adults
- Genetic
- Drug and toxin exposure
- Disease associated with PAH: CHD, HIV, connective tissue disorders
treatment:
Medications specifically for treatment of PAH
CCB in responders
Lung transplantation
Hemodynamic definitions
PH: mean pulmonary artery pressure: > 20mmHg
PAH: mean pulmonary artery pressure: > 20mmHg; pulmonary artery wedge pressure: </= 15mmHg; pulmonary vascular resistance: > 2 wood units
Hemodynamic Definitions
- Pulmonary arterial wedge pressure
– Estimates left atrial pressure
– Normal = 4-12 mmHg
– Elevated numbers signal LV failure or mitral stenosis - Pulmonary vascular resistance
– Calculated using formula based on mPAP and PAWP
PAH Epidemiology (Group 1)
- Rare
– 2-7.6 cases per million adults/year
– prevalence 10-26 per one million adults - Variable age @ diagnosis
– Mean 50 ± 14 years
– 4 x more common in women - Underrecognized
– Median 1.1 years to diagnostic right heart catheterization (gold standard for diagnosing)
– 1 in 5 symptomatic > 2 years before diagnosis - Prognosis is poor but improving
- Approx 15% mortality within 1 year * Median survival 6 years
Negative predictors: - Advanced functional class
- Poor exercise capacity
- High right atrial pressure
- Right ventricular dysfunction
- Low cardiac output
Signs & Symptoms
27% reported fatigue
15% reported fainting or light-headedness
22% reported chest pain
86% reported shortness of breath
13% reported palpitations
21% reported edema
frequently misdiagnosed as asthma
Diagnosis
echocardiogram: Useful for evaluating potential causes, RV function, estimating PAP and PVR (ultrasound of heart)
right heart catheterization: Confirms diagnosis and estimates severity; Assess response to pulmonary vasodilators before starting therapy (AVT); acute vasoreactivity test to see if candidates for CCBS
exercise testing: Distance walked in 6 minutes
biomarkers: BNP and NTproBNP
PH Centers
- If PH suspected, guidelines suggest early evaluation at PH Center
- Accreditation for adult and pediatric programs through Pulmonary Hypertension Association
- Access to specialty physicians, allied health, diagnostics, active research program
- Approx. 9 pediatric centers nationwide (Riley = closest)
- IN Adult Centers: St. Vincent, IU Health
Effects of PAH
- Right side of heart has difficulty pumping against high pulmonary pressures
- Leads to right ventricular failure
PAH Disease Progression
Vascular injury: endothelial dysfunction - decrease nitric oxide synthase, decrease prostacyclin production, increase thromboxane production, increase endothelin 1 production
where the drugs act; want to try to slow this vascular injury process
WHO Functional Classes
class 1: Symptom-free when physically active or resting (at risk, don’t receive tx)
class II: Slight limitation of physical activity – ordinary activity may cause symptoms; Comfortable at rest
class III: Marked limitation in physical activity – less than ordinary activity causes symptoms; Comfortable at rest
class IV: Significant symptoms with activity; Symptoms at rest
worse functional class, your mortality is worse
Risk Assessment in PAH
- Stratification in European guidelines based on low (<3%), intermediate-low (2-7%), intermediate-high (9-19%), or high (>20%) risk of 1-year mortality
– Registry data suggest risk model helps predict mortality
– Use additional criteria as needed (age, renal function, comorbidities, etc) - US guidelines focus on WHO functional class, but clinician discretion will shape treatment
Treatment of PAH
- Goals of therapy
– Alleviate symptoms
– Improve quality of life
– Prevent or delay disease progression
– Reduce hospitalization
– Improve survival
Pharmacotherapy
- Calcium channel blockers (CCB)
- Direct pulmonary vasodilator (inhaled nitric oxide - iNO)
- Phosphodiesterase 5 (PDE-5) inhibitors
- Endothelin receptor antagonists (ERAs)
- Prostacyclins (oral, inhaled, parenteral)
- Soluble guanylate cyclase (sGC) stimulator (riociguat)
Things to Remember
- Head-to-head comparisons of therapies still emerging
- Different drugs have different safety profiles/ADRs
- Consider patient values/preferences/goals
- Cost/insurance
rare disease state makes it harder to study
Guideline Recommendation: AVT
acute vasoreactivity testing –> positive responder –> CCB
acute vasoreactivity testing –> negative responder, RV failure, or CCB contraindication –> do not use CCB
Acute Vasoreactivity Test (AVT)
- Done in cath lab during initial hemodynamic evaluation
- Acute response to pulmonary-specific vasodilators predicts response to
calcium channel blockers - Agents used include – Inhaled nitric oxide – IV epoprostenol
- Positive test = drop in mPAP > 10 mmHg w/PAP less than 40 mmHg w/stable-improved cardiac output
Calcium Channel Blockers
- Only 5-8% of patients are responders; long-term response is rare
- Consider CCBs in positive responders without right-sided failure or other
contraindication to CCB; do not use w/out positive AVT - Recommended drugs
– Long-acting nifedipine 120-240 mg daily – Long-acting diltiazem 240-720 mg daily – Amlodipine 20 mg daily - NO verapamil due to negative inotropic effects
- If patients do not improve to functional class I or II after CCB initiation,
start additional or alternative PAH therapy
Guideline Recommendation: WHO FC I
treatment naive PAH patients w/ WHO FC I –> continued monitoring for disease progression –> determine when to start therapy
* PAH FC I patients do not necessarily require immediate drug therapy; consider CCB if responder
* Monitor closely and consider initiation if worsening symptoms (dyspnea on exertion, fatigue, weakness) or concern for disease progression
Guideline Recommendation: WHO FC II
treatment naive PAH with WHO FC II –> tolerate combo therapy –> yes: combo treatment –> ambrisentan + tadalafil
treatment naive PAH with WHO FC II –> tolerate combo therapy –> no: monotherapy –> ERA, riociguat, or PDE-5 inhibitor
* PAH FC II patients who fail/are not candidates for CCBs should receive targeted PAH therapy
* Combination therapy may increase costs and risk of ADRs – Some patients may prefer to start with monotherapy
– May have comorbidities that require caution
Guideline Recommendation: WHO FC III
treatment naive PAH with WHO FC III w/o rapid progression or poor prognosis –> tolerate combo therapy? –> yes: combo therapy –> ambrisentan + tadalafil
treatment naive PAH with WHO FC III w/o rapid progression or poor prognosis –> tolerate combo therapy? –> no: monotherapy –> ERA, riociguat, or PDE-5 inhibitor
