PAH Best care approach for ED 9 13 10.ppt [Read-Only] · Myxoma Cor triatriatum ... • Right...
Transcript of PAH Best care approach for ED 9 13 10.ppt [Read-Only] · Myxoma Cor triatriatum ... • Right...
“A Best Practices Approach to Treating Pulmonary Hypertension for
the ED and Acute Care Provider”
Sean M. Studer, MD, MScChief, Pulmonary & Critical Care
Director, Pulmonary Hypertension& Lung Transplantation
Newark Beth Israel Medical Center
Disclosures
• Promotional speaker: Actelion, Gilead, United Therapeutics/Lung Rx
• Research funding: Actelion, Gilead, United Therapeutics/Lung Rx
• No off label discussion of medications
Lecture Goals: PAH
• Summarize diagnosis/classification of PAH• Describe lower v. higher risk patients• Review current medication therapies • Analyze approaches to managing
emergencies in PAH
Pulmonary Arterial Hypertension:Definition
• Mean PA pressure > 25 mmHg with PCW <15 mmHg– (NIH Registry on PPH, 1987)
• PVR = 3 Units
• ??Exercise mean PA pressure > 30 mmHg
PVR = TPG/CO
TPG = PAM-PCW
World Conference on Pulmonary Hypertension Revised Nomenclature and ClassificationDana Point 2008
I PAH • iPAH• Heritable PAH• Collagen vascular disease• Congenital L to R shunts• Portal pulmonary HTN• HIV• Drugs (e.g. anorexigens)• PPHN
II Pulmonary venous HTN• Left heart disease
III PH assoc with hypoxia• COPD• Interstitial lung disease (IPF)• Sleep disordered breathing• High altitude
IV ThromboembolicV Multifactorial (e.g. sarcoid)
PAH Pulmonary hypertension
At Risk Populations for PAH: WHO Gr. I
Impact of PAH
• Annual incidence: 15/million pop.; 6/mil iPAH• Orphan disease by US Food & Drug Admin. • Demographics of affected patients:
– More common in women– Mean age at diagnosis 36 years; All ages affected
(Ann Int Med 1987;107:216-23, Chest 2007;131:5-6)
Idiopathic PAH: Survival Without Treatment
adapted from D’Alonzo GE, et al. Ann Int Med 1991;115:343-49
Est. Median survival: 2.8 yrs(95% CI, 1.9 to 3.7 years)
68%
48%34%
0
20
40
60
80
100
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5
Years of follow up
Su
rviv
al (
%)
Assessment of PAH:History I: Signs and Symptoms
– Initial signs and symptoms• Dyspnea – Fatigue• Syncope – Edema• Dizziness – Angina
– Non-specific nature of complaint can lead to:• Confusion with other conditions• Delayed diagnosis (~18-36 months)
(Galie N, et al. Lancet 2008; 371:2093-2100)
Assessment of PAH:Physical Examination
• RV lift /heave• Increased P2• TR, PI murmurs• Signs of congestion• Right-sided extra heart sounds
VC RA RV PAPC
PV LA LV Ao
HTN
DCM HCM
MS Myxoma Cor triatriatum
Anomalous PV PVOD
COPD IPF
PE PPS
PHTN: Where’s the Lesion?
PAH-a pre-capillaryarteriopathy
Findings on Electrocardiogram
• RVH, RAE, RAD, RV strain, [RBBB]-typical
• Arrhythmias not typical- may need ED attn
Chest X-Ray in PAH
RV, right ventricular.McLaughlin VV et al. J Am Coll Cardiol. 2009;53:1573-1619.
Prominent CentralPulmonary Artery
PeripheralHypovascularity
Right DecendingPulmonary Artery
RV Enlargement
Assessment of PAH:Echocardiography
• RV size and function• Right atrial size• Tricuspid regurgitation?• Estimated RV systolic pressure• Dilation, flow reversal of IVC?• Pericardial effusion?• Lack of left sided chamber and valve
abnormalities
Echocardiogram-Severe iPAH
Pericardial Effusion in PAH• Small- moderate effusions are sign of
higher risk due to elevated underlying pressures. No emergent intervention generally…
• Tamponade is not uncommon and ECG/echo may be helpful in confirming--drainage of effusion may be warranted.
PAH: Diagnostic Evaluation
H&P, ECG, CXR ? PH
Echo
PH; left heart dz, congenital R to L shunt
No evidence of PH
Serologies CVD, HIV
V/Q, chest CT, PFT, sleep study Thromboembolism, intrinsic lung dz
RHCIPAH FPAH 6MWT
Pulmonary Arterial Hypertension:Goals of Medication Therapy
• Improve functional class/QOL
• Improve exercise capacity
• Prevent clinical worsening
• Improve survival
• Improve hemodynamics (?)
Therapeutic Targets for PAH
Humbert M, Sitbon O, Simonneau G. N Engl J Med 2004;351:1425-36
Phosphodiesterase type 5 inhibitor
Exogenous nitric oxide
Endothelinreceptor antagonists
Prostacyclin derivatives
Endothelinreceptor A
Endothelin 1Nitric oxide
Prostacyclin (prostaglandin I2)
Endothelinreceptor B
Vasodilation and antiproliferation
Vasodilation and antiproliferation
Vasodilation and antiproliferation
cGMP
cAMP
Pre-proendothelinà Proendothelin
L-arginineà L-citrulline
Arachidonic acid à Prostaglandin I2
++
Phosphodiesterase type 5
Smooth muscle cells
Endothelincells
Vessel lumenNitric oxide pathway
Endothelin pathway Prostacyclin pathway
PAH Determinants of Risk
McLaughlin and McGoon. Circulation 2006;114:1417-31
Lower Risk Determinants of Risk Higher Risk
No Clinical evidence ofRV failure Yes
Gradual Progression Rapid
II, III WHO class IV
Longer (>400 m) 6MW distance Shorter (<300 m)
Minimally elevated BNP Very elevated
Minimal RV dysfunction
Echocardiographicfindings
Pericardial effusion,significant RV dysfunction
Normal/near normalRAP and CI Hemodynamics High RAP, low CI
Emergency issues on therapy:General considerations
• Involve specialty pharmacy early- if infusion drug pump will usually be labeled with toll-free phone #
• Contact PAH program for more information re: patient
• Emergency issues not well studied-patients use support group rec’s; we’ll review by type of therapy
Endothelin is a KeyPathogenic Mediator *
Clozel. Ann Med. 2003: 35; 1-5.
Proliferationvascular smooth musclefibroblasts
Fibrosisfibroblast proliferationá extracellular matrix proteins↓ collagenase production
Inflammationá vascular permeabilityneutrophil / mast cell activation promotes cellular adhesioná cytokine production
Hypertrophycardiac/vascular
Vasoconstrictiondirect or via facilitation of other vasoconstrictor systems (reninangiotensin system, sympathetic)
ET
* Based on animal, in-vitro, and human hemodyamic models
Endothelin Receptor Antagonists• Bosentan (Tracleer)
• Improves walk distance and functional class
• FDA approved for class II-IV PAH
• LFTs, pregnancy concerns
• Ambrisentan (Letairis)
• Once daily dosing, Class II-IV PAH
• Improves six minute walk distance
• LFTs, pregnancy concerns
Emergency Issues-ERAs• Liver enzyme abnormalities (AST/ALT)-few
cases of unexplained hepatic failure
• Lower extremity edema- usually not an emergency but can be misinterpreted as sign of another condition
• Worsening of disease can present as low cardiac output; may need more therapy
PDE 5 inhibitors
• Sildenafil (Viagra, Revatio)• FDA approved for class II-IV PAH• Oral, well-tolerated• Usual PDE 5 inhibitor concerns
• Tadalafil (Cialis, Adcirca)– Oral, once daily dosing– FDA approved for class II-IV PAH
Emergency issues: PDE-5i
• Priapism• Visual changes- often reversible with
drug cessation• Hypotension with nitrate therapy• Worsening of PAH may present with
reduced cardiac output
Epoprostenol (Flolan® & generic) and RTS- Epoprostenol
• Continuous IV Rx, half life of minutes
•Expensive, Requires ice packs unless RTS-epoutilized
• Significant adverse effects-GI, Musc-skel.
AutoCadd Legacy Pump
Room temp. stable epoprostenol(Veletri)
• Does not require ice packs at room temp (77 degrees F)
• Reconstituted with saline or sterile H2O• For NYHA Class III-IV patients• Same half life of minutes
Treprostinil (Remodulin®)
•Stable at room temperature; longer half-life•Continuous IV or SQ •Smaller pump (SQ) •Limiting factor traditionally was site pain•Typical prostacyclin side effects
Emergency issues: Infusion Prostacyclin Therapy
• Deliver system complications:– Catheter-related blood stream infection– Catheter-related thrombosis, bleeding, etc
• Abrupt cessation may result in rebound PAH-always try to continue infusion- peripheral IV is OK
• GI adverse effects may lead to volume depletion; High output cardiac state not uncommon
Iloprost Inhalation Solution: Dosage and Administration
• 6-9 inhalations daily during waking hours– No more than once every two
hours-Most patients ~5 x daily• Dose: 2.5 or 5 mcg delivered• Dosed via prodose AAD system
• Adverse effects (with rate >5% placebo subtracted) include flushing, cough, headache, trismus, insomnia, hypotension, vomiting, increased alkaline phosphatase
Optineb-ir Device Overviewfor inhaled treprostinil
• “Tyvaso inhalation system”
• Inhaled tre. dosing – 4x daily (~2-3 minutes
per treatment)
• “Repetitive-breath”system– Patient must manually
time each inhalation
Inhaled Rx: Emergency Issues
• Abrupt withdrawl is not a consideration• In absence of delivery device usually
not advisable to use alternative nebulizer device
• Ask family/friends to get patient’s device or consider alternative treatment option
Summary: Emergencies in PAH on Medication Therapy
#1. Obtain current treatment to identify risks; e.g. no nitrates with PDE-5 Rx
#2. Infusions are almost never abruptly discontinued and require special handling- contact specialty pharmacy and patient’s PAH prescriber
#3. Acute risks include pericardial effusion and low cardiac output- echocardiography often essential
Conclusions: Best practices for PAH
• Proper diagnosis and classification of PAH is critical to best practice
• Titrate approach for high vs. low risk pts • Understanding current therapies will improve
emergency response• Focused testing, involving specialty
pharmacy /PAH program quickly will add information and promote best decisions