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Overview DefinitionTypesEtiologyBackground:
Pathophysiology
Risk factors
SymptomsDiagnosis Classification Complications Treatment News
Definition Normal pulmonary artery
pressure is 8-20 mm Hg at restPulmonary hypertension is
pressure in the pulmonary artery that is greater than 25 mm Hg at rest or 30 mmHg during physical activity
Types Group 1 PAH (pulmonary arterial hypertension)
Group 2 PH (left heart disease)Group 3 PH (lung disease)Group 4 PH (thromboembolic
disease)Group 5 PH (multifactorial)
Etiology Estimated prevalence of 15-50 cases per
million Approximately 10% of patients
diagnosed with pulmonary arterial hypertension (PAH) have a family history of the disease ◦Referred to as having familial PAH (FPAH)
Idiopathic PAH (IPAH) has an annual incidence of 1-2 cases per million people in the US and Europe
Higher incidence in women
Background: Pathophysiology Life-threatening condition that
gets worse over time◦It is high blood pressure (BP) in the
arteries that go from the heart to the lungs
Can be genetic or caused by another condition
Background: Pathophysiology
Platelets, fibroblasts, and circulating cells are involved in the progression of PAH
The phenotypical change of pulmonary arterial smooth muscle cells (PASMCs) and pulmonary arterial endothelial cells (PAECs) results from multiple genetic and acquired defects and is probably the major cause for the onset of the disease◦ Increased PASMC contraction, increased PASMC
proliferation and inhibited PASMC apoptosis, monoclonal PAEC proliferation, and endothelial injury all are involved in the development of sustained pulmonary vasoconstriction, lumen obliteration of small pulmonary arteries with plexiform lesions, and pulmonary vascular wall thickening due to medial hypertrophy
Risk factors Congestive heart
failure Blood clots in the
lungs Family history Lupus Scleroderma
EmphysemaChronic bronchitisPulmonary fibrosisSleep apnea CirrhosisHIV/AIDsSex (young
female)Drug induced
Risk factors: Drug induced Definite Possible Aminorex Cocaine Fenfluramine Phenylpropanolamine Dexfenfluramine St John's Wort Toxic rapeseed oil Chemotherapeutic agents
Benfluorex Selective serotonin reuptake inhibitors
Dasatinib PergolideLikely Unlikely Amphetamines Oral contraceptives L-Tryptophan Oestrogen Methamphetamines Cigarette smoking
Symptoms Shortness of breath (SOB)
◦Usually, starts slowly and gets worse over time
Chest pain (CP)Fatigue or dizziness (syncope) Passing out Swelling in the ankles and legs
(edema) Racing pulse or heart palpitations
Diagnosis Hard to spot/diagnose because it
mimics those of other similar conditions◦Will assess medical history and use
one or more tests (ie. blood test, chest X-ray, CT scan, MRI, electrocardiogram, echocardiogram, heart catheterization, pulmonary function test, lung biopsy)
Classification Class I. Diagnosed with pulmonary
hypertension, you have no symptoms with normal activity
Class II. Have symptoms at rest, but you experience symptoms such as fatigue, shortness of breath or chest pain with normal activity
Class III. Comfortable at rest, but have symptoms when active
Class IV. Symptoms with physical activity and while at rest
Complications Right-sided heart enlargement
and heart failureBlood clots Arrhythmia Bleeding
Treatment overview
Figure Legend: Evidence-Based Treatment AlgorithmAPAH = associated pulmonary arterial hypertension; BAS = balloon atrial septostomy; CCB = calcium channel blockers; ERA = endothelin receptor antagonist; sGCS = soluble guanylate cyclase stimulators; IPAH = idiopathic pulmonary arterial hypertension; i.v. = intravenous; PDE-5i = phosphodiesterase type-5 inhibitor; s.c. = subcutaneous; WHO-FC = World Health Organization functional class.
Treatment: Non-pharmacologic Salt and volume management Supervised exercise (not too
strenuous) Avoiding pregnancy
◦The mortality rate approaches 30 percentImmunization
◦Specifically, influenza and pneumococcal Improving diet Psycho-social support
Treatment: Pharmacologic All: anticoagulants ± diuretics ±
digoxin ± oxygen◦Long-term oxygen therapy is
suggested to maintain arterial blood O2 pressure at 60 mmHg
Treatment: Pharmacologic Acute vasoreactive testing (IPAH or
APAH, ONLY)◦Positive: use high dose oral CCB (ie.
nifedipine, diltiazem, or amlodipine) use long term
◦Negative: depends on risk Low/High risk: endothelin receptor antagonist
(ERA) or Phosphodiesterase Type 5 (PDE5) Inhibitors (oral), [prostanoids: epoprostenol (IV) or treprostinil (IV/SC), Iloprost (inhaled)], soluble guanylate cyclase (sGC) stimulators
Treatment: Pharmacologic Low or intermediate risk:
monotherapy or oral combination therapy
High risk: combination therapy including IV prostacyclin analogs
Treatment: Pharmacologic Prostanoids:
◦ Epoprostenol (Flolan, Veletri): 2 ng/kg/min IV infusion every 15 min (initial) MOST COMMON
◦ Treprostinil (Remodulin, Tyvasco): Remodulin (IV) = 1.25 ng/kg/min continuous SQ or
central line IV infusion (initial) Tyvasco: QID inhalation
◦ Iloprost (Ventavis): 2.5 -5 mcg/inhalation 6-9x/day Class AE: D/N/V (dose limiting), flushing,
hypotension, anxiety, chest pain, tachycardia, edema◦ Chronic use: anxiety, flu-like symptoms, and jaw
pain (lockjaw with Iloprost)
Treatment: Pharmacologic ERAs:
◦ Bosentan (Tracleer): 62.5 mg PO bid x 4 wks and then 125 mg bid BBW: hepatotoxicity and Cat X CI:cyclosporin and glyburide AE: HA, decrease Hgb, anemia, increase LFTs, upper respiratory
tract infections, edema, male infertility Monitor: LFTs
◦ Ambrisentan (Letairis): 5 or 10 mg PO qd BBW: Cat X AE: peripheral edema, HA, decrease Hgb, flushing, palpitations,
congestion Monitor: Hgb and hematocrit
Macitatan (Opsiumit): 10 mg PO qd◦ BBW: hepatotoxicity and Cat X◦ CI: strong inducers of 3A4 ◦ AE: anemia, cold-like symptoms, bronchitis, HA, flu and UTI◦ Monitor: LFTs
Treatment: Pharmacologic PDE-5 Is:
◦Sildenafil (Revatio): 10 mg IV tid OR 20 mg PO tid (4-6 hr apart)
◦Tadalafil (Adcirca): 40 mg PO qd OR 20 mg PO qd with mild – moderate renal/hepatic impairment (avoid with CrCl < 30 mL/min)
Class ◦CI: nitrates or sildenafil with PI based
regimen, severe hepatic impairment ◦AE: dizzy, sudden drop in BP, HA, flush,
dyspepsia, back pain (Adcirca), and epistaxis
Treatment: Pharmacologic sGC stimulant:
◦Riociguat (Adempas): 1 mg PO TID (initial) Antacids decrease absorption and should
not be taken within 1 hr of taking medication
BBW: Cat X (do not become pregnant during and 1 month after treatment)
CI: nitrates or NO donors, PDE inhibitors AE: HA, dyspepsia and gastritis,
dizziness, N/D/V, hypotension Monitor: BP (baseline and every 2 weeks)
Treatment: Pharmacologic If fail therapy, add another agentIf fail that, lung transplant or
atrial septostomy (Last option)
News FDA approved Uptravi (selexipag)
tablets to treat adults with pulmonary arterial hypertension (PAH): approved through the Orphan drug designation ◦Developed by Actelion
Selexipag is a selective prostacyclin-receptor agonist that targets a well-known disease pathway that opens blood vessels to the lungs and improves heart function
Thank you November is pulmonary hypertension month !!!!
Questions
References http://
www.healthline.com/health/pulmonary-hypertension/how-pah-diagnosed#Tests5 http://www.webmd.com/lung/pulmonary-arterial-hypertension#1-4 https://
dcri.org/events/presentations/pulmonary-hypertension-2014/Fortin-Non%20Pharmacologic.pdf
http://content.onlinejacc.org/article.aspx?articleid=1790601 http://circ.ahajournals.org/content/111/5/534 http://
www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm478599.htm http://familydoctor.org/familydoctor/en/diseases-conditions/pulmonary-hypertens
ion/causes-risk-factors.html http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/docs/fs_pulmonary_hyperte
nsion.pdf
http://www.pah-info.com/How_common_is_PAH http://
www.mayoclinic.org/diseases-conditions/pulmonary-hypertension/symptoms-causes/dxc-20197481
http://reference.medscape.com/drug/adempas-riociguat-999863#4 http://
www.lung.org/lung-health-and-diseases/lung-disease-lookup/pulmonary-arterial-hypertension/risks-symptoms-pul-arterial-hypertension.html
