Pulmonary Hypertension Flashcards
What is Pulmonary arterial hypertension?
Pulmonary arterial hypertension (PAH) is a progressive, incurable disease of the small pulmonary arteries, characterized by vascular cell proliferation, aberrant remodeling, and thrombosis in situ. • PAH is a syndrome characterised by a progressive increase in pulmonary vascular resistance (PVR) – leads to right ventricular overload – eventually leads to right ventricular failure and premature death1 – If untreated, the median survival is 2.8 years2 which is comparable with some malignancies • Increased PVR is related to progressive changes in the pulmonary arterioles – vasoconstriction – obstructive remodelling of the pulmonary vessel wall – inflammation – in-situ thrombosis
Why does Pulmonary Arterial Hypertension (PAH) develop? What are the principle focus of research for treating PAH?
• Reduced production of vasodilators – Prostacyclin • potent vasodilator • potent inhibitor of platelet activation • therapy with synthetic forms of prostacyclin may help to correct this deficiency – Nitric oxide • potent vasodilator • possesses anti-proliferative properties • vasodilatory effect is mediated by cGMP –rapidly degraded by phosphodiesterases • Increased production of vasoactive compounds – Endothelin (ET) • elevated levels are seen in PAH patients13 • levels correlate with disease severity4 • deleterious effects mediated through endothelin receptors5 –fibrosis –hypertrophy and cell proliferation –inflammation –vasoconstriction • endothelin receptor antagonists can block these effects • Endothelin, nitric oxide and prostacyclin have been the principal focus of research into treatments for PAH
Definition of PAH (clinically)? Symptoms?
• Sustained elevation of mean pulmonary arterial pressure (mPAP)1 – >25mmHg at rest • Normal pulmonary capillary wedge pressure – 15mmHg • Earliest symptom is often dyspnea on physical exertion • Other symptoms may include2,3 – syncope or near syncope – fatigue – peripheral edema – chest tightness – chest pain on physical exertion
Classifications of PAH?
1). PAH– Idiopathic PAH – Familial (Heritable) PAH – Associated with: • Connective tissue disease • BMPR2, ALK1, endoglin • CHD (shunts) • Portal hypertension • HIV infection • Sickle cell disease • Drugs and toxins • Other (thyroid) – Persistent pulmonary hypertension of the newborn 2. PH associated with left heart disease- Diastolic, Systolic or Valvular disease 3. PH associated with respiratory disease – COPD – Interstitial lung diseases 4. PH due to chronic thrombotic and/or embolic disease 5. Miscellaneous (sarcoidosis, glycogen storage disease)
How is the severity of PAH classified?
• Classified according to a functional class system– New York Heart Association (NYHA)/ World Health Organization (WHO) • There are four WHO functional classes (WHO FC)– WHO FC I being the least severe – WHO FC IV being the most advanced – different classes reflect the impact on a patient’s life in terms of physical activity and symptoms
Survival in PAH?
• Survival rates (patients with IPAH) at 1, 3 and 5 years were 68%, 48% and 34% respectively • PAH mortality contributed to • Right heart failure 47% • Sudden Death 26% • Other (pneumonia) 27% • Although new treatments have improved mortality rates, there is little evidence to support reversal of aberrant remodeling
How common is PAH?
• PAH is rare – an estimated prevalence of 3050 cases per million– most common in young women • Mean age of diagnosis 36 years2 • The prevalence in certain at-risk groups is higher – HIV-infected patients (0.50%)3 – sickle cell disease (2040%)4 – systemic sclerosis (16%)5 • True prevalence may be higher
Do we have an exact pathophysiology on PAH?
• Exact cause of PAH remains unknown • Endothelial dysfunction occurs early on in the disease process • Endothelial dysfunction results in – reduced production of vasodilators – over production of vasoconstrictors – endothelial and smooth muscle cell proliferation – remodelling of the pulmonary vascular bed and increased vascular resistance
what are the symptoms of PAH?
- High resistance to blood flow through the lungs causes right heart dysfunction and produces: – dyspnea – fatigue – dizziness – syncope – peripheral oedema – chest pain, particularly during physical exercise
- Symptoms are non-specific and are commonly attributed to other conditions
- Over time, symptoms become more severe and limit normal daily activities
What is crucial in PAH? Why?
Early diagnosis is crucial
• If untreated, the median survival is 2.8 years which is comparable with some malignancies
• diagnosis can be delayed for months or years and frequently occurs when disease is relatively advanced
- mean time from onset to diagnosis is estimated to be approximately 2 years5
- Although patients progress at different rates; early stage PAH is still a devastating condition and can rapidly deteriorate
- Early diagnosis and intervention is therefore crucial
• patients who begin targeted therapy in less severe PAH (WHO FCI/II) demonstrate a better prognosis than those in a more severe stage (WHO FCIII/IV)6
How is PAH diagnosed?
i. Clinical suspicion of pulmonary hypertension- symptoms, screening and incidental findings
ii. Detection of pulmonary hypertension- ECG, chest radiograph, Doppler echocardiography
iii. Identification of other causes of pulmonary hypertensionpulmonary function test, blood gas samples, HRCT
iv. PAH evaluation and classification- functional capacity and hemodynamics
which patients do we screen with ECHO for PAH?
• High clinical suspicion based on clinical exam, etc • CTD (Systemic Sclerosis (SSc) ,Lupus, RA, Scleroderma) • Liver transplant candidates • Shunts • Amphetamine Derivatives • Family members of a patient with familial Pulmonary Arterial Hypertension (FPAH) • Patients with HIV
Why is PAH hard to diagnose?
- Low awareness/not a condition seen every day by general physicians
- It often comes in disguise: • Non-specific symptoms that are often mild and common to other conditions • Confusion with other diseases such as asthma, COPD and other cardiovascular disorders
- Patients typically see many health professionals before diagnosis
- No simple means of excluding PAH
Pulmonary Venous hypertension etiologies?
• Valvular heart disease (HD) • Hypertensive HD • Cardiomyopathies • Transmitted pressure results in reactive vasoconstriction
Treat the primary problem!
Restrictive lung diseases that can be associated with PH?
Neuromuscular diseases Kyphoscoliosis* Thoracoplasty Sequelae of pulmonary tuberculosis Sarcoidosis Pneumoconiosis Drug-related lung diseases Extrinsic allergic alveolitis Connective tissue diseases Idiopathic interstitial pulmonary fibrosis* Interstitial pulmonary fibrosis of known origin
Optimal treatment strategy for PAH?
Blank: Vasodilatory study.
What are the prostacyclins used to treat PAH? Long term outcomes treating IPAH with prostacyclins?
• Intravenous (epoprostenol, treprostinil)* • Subcutaneous (treprostinil*) • Inhaled (iloprost*, treprostinil†) • Oral (beraprost‡, treprostinil†))
