1. Katie DePlatchett M.D. AM Report June 29, 2010

2.  Elevated Pulmonary Artery pressure  Secondary R Ventricular failure  Mean Pulm Artery Pressure of >25mmHg at rest  Pulmonary capillary wedge pressure (PCWP) <15mmHG ◦ Diagnosed by Right Heart Catherization (RHC)

3.  Ohm’s Law: P = Q x R Pa- Pv = CO (right sided) x PVR Pa = (CO x PVR) + PCWP  PVR: occlusion of small arterioles, hypoxic vasoconstriction  CO: congenital defects (shunts), cirrhosis  PCWP: systolic HF, valvular dx

5.  intimal hyperplasia and fibrosis, medial hypertrophy, and in situ thrombi of the small pulmonary arteries and arterioles

6.  Previously idiopathic PAH vs secondary PAH  Amended to groups (Group 1-5) based on etiology

7.  Idiopathic  Heritable  Disease which localize to small pulm arterioles ◦ connective tissue disease, HIV, portal htn, chronic hemolytic anemia, congenital  Drug or toxin induced ◦ amphetamines, cocaine, appetite suppressants (fen-fen), chemotherapies, St. John’s wort, SSRIs

8.  PH secondary to L heart disease (G2) ◦ systolic, diastolic, valvular dx  PH secondary to lung dx or hypoxemia (Group 3) ◦ COPD, ILD, OSA, Hypoventilation  Chronic thromboembolic PH (Group 4)  PH due to “unclear multifactorial mechanisms” (Group 5) ◦ Heme, systemic (sarcoidosis), metabolic (glycogen storage dx)

9.  Increased intensity of pulmonic component of 2 nd heart sound or split P2  Systolic ejection murmur over LSB  Diastolic murmur over LSB (d/t pulm regurg)  R-sided S3 or S4  Elevated JVP  Peripheral edema  Hepatomegaly, ascites

10.  CXR: enlargement of the central pulmonary arteries with attenuation of the peripheral vessels  ECG  R heart strain, RAD  Echo  estimate the pulmonary artery systolic pressure and to assess right ventricular size, thickness, and function ◦ PH is likely if the PASP is >50 and the TRV is >3.4

12.  Labs: HIV, LFTs, ANA, RF, ANCA, ? evidence of chronic hemolytic anemia  PFTs to identify and characterize underlying lung disease that may be contributing  Overnight oximetry to assess nocturnal oxyhemoglobin desaturation  Sleep study for eval of OSA  V/Q scan for chronic thromboemboli

13.  Right Heart Catherization ◦ necessary to confirm the diagnosis of PH and accurately determine the severity of the hemodynamic derangements  6 min walk ◦ To determine functional status ◦ Assist with prognosis ◦ Some cases are exercised induced

15.  Class: I Ordinary physical activity does not cause undue fatigue or dyspnea, chest pain, or heart syncope.  Class II: Slight limitation of physical activity. Ordinary physical activity results in undue fatigue or dyspnea, chest pain, or heart syncope.  Class III: Less than ordinary physical activity causes undue fatigue or dyspnea, chest pain, or heart syncope.  Class IV: Inability to carry on any physical activity without symptoms. Usually manifest signs of right heart failure. Dyspnea and/or fatigue may be present even at rest.

16.  Oxygen  Diuretics  Anticoagulation for groups 1 & 4 ◦ intrapulmonary thrombosis & thromboembolism, due to sluggish pulmonary blood flow, dilated right heart chambers, venous stasis, and a sedentary lifestyle ◦ Warfarin therapy w/ INR target of 2.0  Exercise…get off that couch! ◦ Improved functional status

17.  Phosphodiesterase 5 inhibitors (sildenafil) ◦ prolong the vasodilatory effect of nitric oxide ◦ SUPER trial, improved HD & exercise capacity, no change in mortality ◦ Class III  Endothelian receptor antagonist (Tracleer) ◦ Endothelin-1 is a potent vasoconstrictor and smooth muscle mitogen ◦ BREATHE-1 trial, improved symptoms, the six-minute walking distance, and the WHO functional class ◦ Class II & III  CCB ◦ Class II & III

18.  Vasoreactivity testing during RHC ◦ Measures HD response to nitric oxide or Flolan ◦ If Pulm artery pressure decreases by 10mm Hg & is <40mm Hg w/o a significant change in CO, then trial of CCB (Diltiazem 120mg daily & titrate) ◦ If negative (no response)  Prostanoids (Flolan, Remodulin)  Prostanoids = prostacyclins ◦ Potent vasodialator & inhibitor of platet aggregation

19.  Symptomatic IPAH w/o treatment have a median survival of ~ 3 years  Symptomatic w/ PAH that is associated with another disease generally have a worse prognosis  Severe PAH or right CHF median survival of 1 year w/o treatment