Pulmonary Hypertension: What you need to know

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Pulmonary Hypertension What you need to know

• William Leeds, DO, FCCP
• Pulmonary Sleep Associates
• Veritas Clinical Specialties
• Topeka, KS

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What is Pulmonary Hypertension?

• Definition
• Right heart catheterization showing
• Sustained elevation of mean pulmonary artery
  pressure gt 25 mmHg at rest

• Secondary RHC parameters
• MPCWP lt 15 mmHg
• PVR gt 3 Woods Units

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WHO Classifications

• Group I Pulmonary Arterial Hypertension
  (estimated 15 cases per 1 million adults)
• Idiopathic (primary)
• Familial
• Drug- and toxin-induced
• Associated with connective tissue disease, HIV,
  portal hypertension
• Associated with significant venous or capillary
  involvement
• Persistent pulmonary hypertension of the newborn

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WHO Classifications, cont.

• Group II Pulmonary Hypertension Owing to Left
  Heart Disease
• Group III Pulmonary Hypertension Owing to Lung
  Diseases or Hypoxemia
• Group IV Chronic Thromboembolic Pulmonary
  Hypertension
• Group V Pulmonary Hypertension with Unclear
  Multifactorial Mechanisms

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WHO Functional Classes of PAH
Class Description
I Patients with PH but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea, chest pain, or near syncope.
II Patients with PH resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope.
III Patients with PH resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope.
IV Patients with PH with inability to carry out any physical activity without symptoms. These patients manifest signs of right-heart failure. Dyspnea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity.
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Pathogenesis of PAH Proliferative Vasculopathy

• Triggers (Initiation Factors)
• Inflammation
• Autoimmunity
• Infection
• Hemodynamic shear stress
• Hypoxia
• Drugs/chemicals/toxins

• Genetic Predisposition
• BMPR-2 and ALK-1 genes
• Kv channels
• Oxygen-sensing mechanisms
• 5-HHT

• Activation Pathogenic Vascular Mediators
• Endothelial dysfunction
• Vasoactive mediators
• Growth factors

Adapted from Gaine S. JAMA. 20002843160-3168. Sl
ide courtesy of Roxanna Sulica, MD.
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Diagnosis of PAH

• Often made late in the disease
• Median duration between symptom onset and
  diagnosis is 27 months

• Late diagnosis due to
• Under-recognition
• Nonspecific symptoms
• Confusion with other conditions
• iPAH is diagnosis of exclusion

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Signs and symptoms of PAH

• No early symptoms
• Progressive DOE, fatigue, palpitations, chest
  pains, cough, hoarseness, syncope
• Symptoms of RHF
• Ascites
• Edema

• Must screen high-risk populations
• Family history of iPAH
• Connective tissue disease
• Pulmonary embolism
• Congenital heart disease

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Prognosis of iPAh is poor with supportive care
only
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PAH/ssc progresses even more rapidly
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Diagnostic workup (CC SOB)

• CXR
• Complete PFT
• Initial labs (CBC, CMP, BNP)
• Physical exam
• Med hx/symptom review
• Echocardiogram

• If echo shows PAH
• VQ scan/CT angio
• Labs (ANA, RF, HIV, ANCA, anti-Scl 70, ESR, CRP)
• Polysomnogram
• 6MWT
• RHC

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Right heart catheterization

• PA pressure
• PCW pressure
• Cardiac output
• PA saturation
• Pulmonary vascular resistance
• Vasodilator challenge
• Exercise challenge

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Treatment options

• Treat the underlying/contributing condition
• Oxygen if needed
• Check 6MWT and nocturnal oximetry
• Oral medications
• Inhaled medications
• IV medications
• Surgical interventions

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Targets for PAH therapy
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Oral medication options for PAH

• Warfarin (iPAH)
• Calcium channel blockers (amlodipine)
• Blocks entry of calcium into heart and muscle
  cells
• Improves ability of heart to pump blood
• Relaxes smooth muscle in walls of heart and
  smooth muscles
• Only a small number of PAH patients respond
• Side effects nausea, h/a, rash, edema,
  dizziness, fatigue

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Oral medication options, cont.

• PDE-5 inhibitors
• Blocks the action of phosphodiesterase
• Dilates pulmonary vasculature
• Side effects vision problems, h/a
• Endothelin receptor antagonists
• Blocks vasoconstrictive effects of endothelin-1
• Dilates pulmonary vasculature
• Side effects liver toxicity and anemia
  (requires routine monitoring), edema

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Inhaled medication options

• Inhaled iloprost (Ventavis)
• Dilates systemic and pulmonary vessels
• Inhaled multiple times daily
• Side effects cough, h/a, throat pain
• Inhaled treprostinil (Tyvaso)
• Dilates systemic and pulmonary vessels
• Inhibits platelet aggregation
• Inhaled multiple times daily
• Side effects cough, throat irritation, h/a

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IV medication options

• IV epoprostenol (Flolan)
• Directly dilates peripheral vessels
• Inhibits platelet aggregation
• Must be initiated in hospital
• Cannot be stopped abruptly
• Side effects h/a, nausea, jaw pain, flushing,
  hypotension

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Surgical options

• Atrial septostomy

• Heart-lung transplant

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Treatment options summarized
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Case Studies

• GL
• BB
• KS

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Case Study GL

• Presented to pulmonary service in September 2006
  at age 53
• Chief complaint was progressive SOB with exertion

• PMH scleroderma dx at age 39, unspecified
  arrhythmia, GERD, depression, allergies,
  arthritis, and migraine h/a
• PSH tonsillectomy

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GL, continued

• Current medications inderal, nexium, miacalcin,
  percocet, tramadol, mucinex, alavert, vitamin C
• Allergies imitrex (unknown reaction)

• FH COPD in father, lung ca and COPD in brothers
• SH 30 pk-yrs of cigarette use quit in 2000

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GL Diagnostics

• CXR 8/20/03 mild decrease of lung volumes and
  mild increased prominence of interstitial
  markings in both lung bases since 1992 Some
  degree of interstitial lung disease cannot be
  ruled out
• PFT 9/19/06 FVC 2.19 L (70), FEV1 1.79 L
  (70), FEV1/FVC 82, IC 1.67 L (77), RV 1.15 L
  (64), TLC 3.44 L (70), Diffusion 36, DL/VA
  2.53 L (55)

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GL Diagnostics, cont.

• Echocardiogram 8/21/06 EF 60-65, abnormal LV
  diastolic filling/impaired relaxation, mild AR,
  mild MR, mild TR, mild PR, RVSP 68 mmHg
• RHC 11/01/06 mean RA 10, mean RV 7, PAP 70/29
  (mean 44), MPCWP 13, CO 4L adenosine trial
  showed decreased MPAP 38
• 6MWT 390 m, O2 sat nadir 92 on room air

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GL Treatment Course

• November 2006 bosentan, sildenafil, and
  warfarin initiated
• August 2007 CT mild bibasilar interstitial
  fibrosis
• October 2007 oxygen added
• 6MWT 183 m O2 sat nadir 83 on room air
• November 2007 transtracheal oxygen initiated
• February 2008 Ventavis added

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GL Treatment Course, cont.

• August 2008 referred to KUMC
• RHC normal EF, RA 8, MPAP 47, MPCWP 12-14, CO
  5.4
• 6MWT 428 m O2 sat nadir 92 on 3L
• CT chest progression of bibasilar fibrosis
• IV prostacyclin held due to stability of RHC
  findings
• October 2008 unable to proceed with lung
  transplant due to financial issues
• May 2009 6MWT 292 m O2 sat nadir 86 on 4L

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GL Treatment Course, cont.

• June 2009
• RHC MPAP 66, MPCWP 22, CO 4.6
• Significant GERD symptoms
• February 2010 transitioned from Ventavis to
  Tyvaso
• July 2010 symptoms acutely worsened
• Hospitalized for hemoptysis
• Hospice discussed

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GL Treatment Course, cont.

• November 2010 last contact
• Echo EF 65, RV severely dilated with moderate
  systolic dysfunction, RA severely dilated,
  moderate TR, PAP 84
• PFT FVC 1.83 (60), FEV1 1.59 (65), FEV1/FVC
  87, TLC 62, Diffusion 11
• Deceased February 2011

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GL Discussion

• Questions/comments?

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Case Study BB

• Presented to pulmonary service in July 2002 at
  age 45
• Chief complaint was progressive dyspnea on
  exertion for last 6 months

• PMH poss. CVA or seizure age 19 w/no further
  recurrence
• PSH none
• FH CAD in father, mother, brother (brother had
  heart surgery at age 46)
• SH no tobacco or illicit drug use

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Case Study BB, cont.

• Current medications Combivent inhaler and
  previous use of prednisone without significant
  improvement in symptoms
• Allergies NKDA

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BB Diagnostics

• PFT 7/10/02 FVC 3.78 L (108), FEV1 2.64 L
  (91), TLC 6.18 l (114), VC 3.78 L (108), RV
  2.4 L (128), Diffusion 94
• ABG on room air 7/19/02 pH 7.395, pCO2 36.8,
  PO2 57.1, BE -2.0, HCO3 21.9, O2 sat 88
• LHC 7/19/02 RA 1, RV 0, MPAP 50, MPCWP 11, CO
  4.21 L
• O2 sat 88 with ambulation

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BB Treatment Course

• July 2002 Placed on Oxygen, digoxin and
  bosentan
• Referred to Mayo Clinic, Rochester MN
• Diagnosed with Primary Pulmonary Htn
• September 2002 initiated on warfarin
• RHC 12/02 RA 7, MPAP 43, MPCWP 15, CO 4.73
  Flolan trial showed MPAP 46, MPCWP 10, CO 7.43
• Amlodipine added

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BB Treatment Course, cont.

• Echo 9/8/03 EF 63, moderate RV enlargement,
  moderately decreased RVSF, RVSP 77
• Echo 11/04 RVSP 74, moderate RV enlargement,
  mild TR
• Echo 02/06 severe RV enlargement, RVSP 81
• February 2006 Sildenafil added
• Care turned over to Mayo Clinic physicians
• Last contact May 2006

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BB Discussion

• Questions/comments?

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Case Study KS

• Presented to pulmonary service August 2011 at age
  46
• Chief complaint was increased dyspnea and LE
  edema x 2 months

• PMH DVT/PE 1996, HTN, DM, hypothyroid, obesity
  and allergies
• PSH none
• FH father died age 48 of AMI HTN, DM
• SH works at a bank, denies cigarette and
  illicit drug use

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Case Study KS, cont.

• Current medications amlodipine, vit E,
  levothyroxine, MVI, losartan/hctz, ASA,
  furosemide, fish oil, metformin, Ca/Vit D,
  omeprazole, warfarin, potassium

• Drug allergies NKDA

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KS Diagnostics

• Labs 7/12/11 BNP 430, Hgb 11.1, Hct 34.6, BMP
  WNL, HIV neg.
• CT 7/22/11 no pulmonary emboli/no acute process
• Cardiac stress test 7/27/11 LVEF 57, dilated
  RV, normal EKG
• Bilateral LE doppler 8/3/11 no DVT
• VQ lung scan 8/3/11 high probability for PE in
  lateral segment of RLL

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KS Diagnostics, cont.

• Echo 7/27/11 normal LVF, abnormal septal motion
  likely r/t right-sided volume overload, trace MR,
  RA and RV significantly enlarged, mod TR, RVSP
  107
• PSG 8/4/11 AHI 106, REM AHI 109, baseline O2
  sat 84, O2 sat nadir 53

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KS Treatment Course

• August 2011 warfarin, nasal CPAP w/O2, and
  weight loss initiated CV meds adjusted
• October 2011 hospitalized for dizziness
  secondary to abnormal uterine bleeding (Hgb 6.2)
• Consideration given to IVC filter
• 098

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Case Study CZ

• First presented to pulmonary service February
  2010 at age 66
• Chief complaint was dyspnea, cough and sputum
  production

• PMH a-fib, chronic bronchitis, HTN, hypothyroid
• PSH constrictive pericarditis surgery
• FH CAD in parents
• SH 20 pk-yrs of cigarette use, no illicit drug
  use

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Case Study CZ, cont.

• Current medications Toprol, warfarin, vit D,
  calcium, ASA, furosemide, levothyroxine,
  albuterol, Benicar, omeprazole, simvastatin

• Allergies cefdinir, penicillin, codeine,
  propoxyphene

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CZ Diagnostics

• PFT 2/12/10 FVC 1.48 L (58), FEV1 1.14 L
  (59), FEV1/FVC 77, TLC 5.03 L (110), VC 2.53 L
  (98), RV 2.5 L, Diffusion 115
• Echo 9/8/10 LV hypertrophy, EF 75, moderate RV
  enlargement with reduced RVSF, mod-severely
  dilated RA, mild TR, RVSP 45-50
• RHC 9/8/10 MPCWP 31, MPAP 43, CO 2.7,
  post-nitric oxide infusion CO 2.7