Therapeutics I Exam VI (Pulmonary HTN) Flashcards
Pulmonary Hypertension
Is the right heart a high pressure or low pressure system?
The right side of the heart is a low pressure system.
What is preload?
This is the amount of stretch the myocardial cells feels at the end of diastole. It is also called end-diastolic volume.
Preload and end-diastolic volume depends on the compliance of the _______ _____.
Muscle wall
Afterload of the right ventricles measures what?
Pulmonary vascular resistance
What is right heart catheterization?
This is a catheter with a balloon tip that can monitor intra-cardiac pressures.
Once the balloon for the right heart catheterization is inflated in the pulmonary artery, the catheter is considered to be _________.
Wedged
When the right heart cath balloon is inflated in the pulmonary artery, the ________ heart and _________ artery diastolic pressures are blocked.
Right heart and pulmonary artery
What does the balloon stop in the right heart catheterization?
The balloon stops blood flow and allows for an uninterrupted column of blood to exists between the catheter and the left atrium.
What is the right heart catheter called?
The Swan-ganz catheter
A right heart catheter is typically placed in what vein?
Jugular vein
When the balloon is placed and the heart is in diastole, what is being measured?
When the heart is filling with the balloon in place, there is a static column of pressure between the pulmonary artery and the left atrium and ventricular. This measure the preload and end-diastolic volume of the left ventricule.
What is PCWP?
Pulmonary capillary wedge pressure
What is PAWP?
Pulmonary artery wedge pressure
What is PAoP?
Pulmonary artery occlusion pressure
What are the 5 things that the Swan-Ganz catheter obtains?
- Wedge pressure (PCWP)
- Cardiac output/index
- Right atrial pressure (measured during diastole so also measures right ventricular preload and pressure)
- Pulmonary artery systolic, diastolic, and mean pressures
- Pulmonary vascular resistance (afterload of right ventricule)
What is the pressure value indicating pulmonary hypertension?
mPAP greater than 20 mmHg
What is defined as pre-capillary pulmonary hypertension?
mPAP greater than 20 mmHg AND PCWP 15 mmHg or less AND pulmonary vascular resistance 2 or more woods unit.
Define pulmonary hypertension.
Marked remodeling of the pulmonary vasculature and a progressive rise in pulmonary vascular load, leading to hypertrophy and remodeling of the right ventricle. Pulmonary HTN is broken into 5 groups that are based on the mechanism of the disease.
What is the description of WHO group 1 for PHTN?
WHO group 1 is pulmonary arterial hypertension (PAH)
What are the potential causes of WHO group 1 pulmonary arterial hypertension?
Idiopathic, congenital, liver disease, portal HTN, HIV, drugs, toxins, connective tissue disorders like lupus or scleroderma.
What is the description of WHO group 2 for PHTN?
WHO group 2 is pulmonary hypertension due to left heart disease
What are the potential causes of WHO group 2 pulmonary hypertension due to left heart disease?
Ventricular systolic/diastolic dysfunction or valvular issues
What is the description of WHO group 3 for PHTN?
WHO group 3 is pulmonary hypertension due to lung disease or hypoxia (prolonged)
What are the potential causes for WHO group 3 pulmonary hypertension due to lung disease of hypoxia?
Obstructive disease like COPD, restrictive diseases like interstitial lung disease or pulmonary fibrosis, and sleep apnea.
What is the description of WHO group 4 PHTN?
Chronic thromboembolic pulmonary hypertension
What are the potential causes for WHO group 4 pulmonary hypertension?
Pulmonary embolism or thrombosis of the pulmonary arteries
What is the description of WHO group 5 PHTN?
WHO group 4 is a catch-all for those with pulmonary hypertension with an unclear or multifactorial mechanism.
What are the potential causes of WHO group 5 pulmonary hypertension?
Sarcoidosis, sickle cell disease, chronic hemolytic disease, splenectomy, or metabolic disorders.
How common is WHO group 1 pulmonary arterial hypertension?
Rare
How common is WHO group 2 pulmonary hypertension due to left heart disease?
Very common
How common is WHO group 3 pulmonary hypertension due to lung disease or hypoxia?
Common
How common is WHO group 4 pulmonary hypertension due to chronic thromboembolism?
Rare
How common is WHO group 5 pulmonary hypertension?
Rare
What describes the WHO class I functionality for pulmonary hypertension?
Pulmonary hypertension without resulting limitation of physical activity. Ordinary physical activity does not cause dyspnea, fatigue, chest pain, or syncope.
What describes the WHO class II functionality for pulmonary hypertension?
Pulmonary hypertension resulting in slight limitation of physical activity. There is comfort at rest but ordinary physical activity may cause fatigue, dyspnea, fatigue, chest pain, or syncope.
What describes the WHO class III functionality for pulmonary hypertension?
Pulmonary hypertension that results in marked limitation of physical activity. There is comfort at rest but less than ordinary activity causes dyspnea, fatigue, chest pain, or syncope.
What describes the WHO class IV functionality for pulmonary hypertension?
Pulmonary hypertension with inability to carry out any physical activity without symptoms. Patients will manifest signs of right heart failure. Dyspnea and/or fatigue may be present as rest and discomfort increases with physical activity.
What are the many risk factors for pulmonary arterial hypertension (WHO class I)?
- Family history of PAH
- Genetic mutation in 1st degree relative
- Limited cutaneous scleroderma or mixed CT diseases
- Exposure to drugs and toxins
- congenital heart disease with surgically repaired left/right shunt within the last 3-6 months
- portal HTN
- HIV
T or F: At risk patients for PAH should not be monitored for the development of PAH.
False. The 2019 chest guidelines and the 2022E European guidelines state that at risk patients should be monitored.
What are the symptoms of pulmonary hypertension?
Fatigue, SIB, dizziness on exertion, peripheral edema, and exertional chest pain
What are the signs of pulmonary hypertension?
- large P waves
- right ventricular hypertrophy
- right axis deviation
- increase in pulmonic heart sounds
- enlarged right side of heart
- reversal of normal septal curvature
In order to actually be diagnosed with pulmonary hypertension, what test must be conducted?
Right heart cathetorization
If there are warning signs of pulmonary hypertension, what needs to be done?
Pulmonary HTN patients with warning signs need to be fast-tracked referred to a designated pulmonary hypertension center.
For pulmonary hypertension screening and diagnosis, what is being looked for in terms of the echocardiogram?
Looking for TAPSE (tricuspid annular plane of systolic excursion). A TAPSE less than 1.7cm is a prognostic indicator for poor outcomes with pulmonary hypertension.
In pulmonary hypertension, there is an imbalance of vascular effects. The imbalances favor was 3 vascular effects?
Vasoconstriction, proliferation, and thrombosis
What are the vascular effectors that are imbalanced in pulmonary hypertension?
Prostacyclins, thromboxane A2, endothelin-1, nitric oxide, serotonin, vasoactive intestinal peptide (VIP), and vascular endothelial growth factor (VEGF).
What are the 3 effects of prostacyclins?
Vasodilation, inhibition of platelet activation and cellular proliferation.
Are prostacyclins elevated or diminished in pulmonary hypertension?
Prostacyclins are low during pulmonary hypertension.
What are the effects of thromboxane A2 in the body?
Vasoconstriction and it promotes platelet activation
Is thromboxane A2 elevated or diminished in pulmonary hypertension?
Thromboxane A2 is elevated in pulmonary hypertension.
What is the function of endothelin-1 in the body?
Vasoconstriction and stimulation of cellular proliferation.
Is endothelin-1 elevated or diminished in pulmonary hypertension?
Endothelin-1 is elevated in pulmonary hypertension.
What is the function of nitric oxide in the body?
Vasodilation, inhibit platelet aggregation, and inhibits cellular proliferation.
Is nitric oxide high or low in pulmonary hypertension?
Nitric oxide is low in pulmonary hypertension
What is the pathophysiology surrounding pulmonary hypertension?
It can be due to pulmonary vasculopathy or right heart failure.
What are the pathophysiologic pathways involved in pulmonary hypertension
- Endothelin pathways
- NO-sGC-cGMP pathway
- Prostacyclin pathway
What are the predictors of poor outcomes with pulmonary hypertension?
- Evidence of right ventricular failure
- Advanced functional class
- Poor exercise capacity test (6min walk test) or cardiopulmonary exercise test
**- High right atrial pressure - Significant right ventricular dysfunction**
- low cardiac index
- ## elevated brain natriuretic peptide
- underlying diagnosis of scleroderma spectrum
What is the most important prognosis indicator in pulmonary hypertension?
Evidence of right ventricular failure. If this is present, the patient will likely not do well.
What are the 5 goals of therapy when it comes to pulmonary hypertension?
- Delay time to clinical worsening
- Reduce morbidity and mortality
- Alleviate symptoms and improve quality of life
- Improve exercise capacity measured by the 6 minuted walk distance test
- Improve cardiopulmonary hemodynamics and prevent right heart failure
What are some lifestyle modifications that can improve pulmonary hypertension?
Sodium restriction, smoking cessation, avoid high altitudes, avoid physical excretion, avoid pregnancy, and stay up to date with vaccines.
What are the 3 pharmacologic interventions done for pulmonary hypertension?
- Supplemental oxygen
- Anticoagulation if CTEPH is indication
- Diuretics to maintain euvolemia
What is pulmonary vasoreactivity testing for?
This is a test conducted on patients suspected of idiopathic, heritable, or drug-associated pulmonary arterial hypertension to see if they are eligible for a calcium channel blocker for their PAH.
The purpose of vasoreactivity testing in PAH is to identify acute vasoresponders who may be candidates for treatment with high-dose calcium channel blockers
What medications are typically inhaled for a pulmonary vasoreactivity test?
Nitric oxide or iloprost
What result from pulmonary vasoreactivity testing indicates a person with PAH is a candidate for calcium channels blockers?
A positive acute response is defined as a reduction in mPAP by ≥10 mmHg to reach an absolute value ≤40 mmHg, with increased or unchanged CO.
Basically, the mean pulmonary arterial pressure is reduced by 10 mmHg or more from baseline to reach a value no higher than 40 mmHg mean pressure in the pulmonary artery. Additionally, there are no changes or increased cardiac output.
What is the only WHO group that would undergo pulmonary vasoreactivity testing to determine eligibility for a calcium channel blocker?
Only WHO group 1, those with pulmonary arterial hypertension
When do you reassess a patient with pulmonary vasoreactivity testing?
3-6 months after the initial test
Less than _______ of those who take the pulmonary vasoreactivity test are responders that qualify to be placed on a calcium channel blocker?
10%
If a patient with group 1 PHTN (PAH) is indicated for a calcium channel blocker, what 3 are typically used?
Amlodipine, nifedipine, or diltiazem
Verapamil is avoided as it is a negative inotrope and the most potent non-DHP CCB.
If a PAH patient is placed on a calcium channel blocker, when should a right heart catheterization be reperformed?
Repeat RHC after 1 year as more than 50% of patient on CCBs have diminished effects overtime.
T or F: Low-dose CCBs are used, if indicated, for those with PAH.
False. If indicated, high doses of CCBs are used for pulmonary arterial hypertension.
For PAH, what is the dose range for amlodipine?
20-40 mg daily
For PAH, what is the dose range for nifedipine?
120-240 mg daily
For PAH, what is the dose range for diltiazem?
240-720 mg daily
T or F: For those on CCBs with PAH, 90% of these patients are still alive in 5 years.
True
For a patient diagnosed with PAH, had a negative vasoreactivity test, and has cardiopulmonary comorbitdies, what is the treatment protocol?
Initiate oral monotherapy of PDE5i (phosphodiesterase 5 inhibitors) or ERA (endothelin receptor antagonists)
What factors via the 3-strata are considered ‘high risk’ for patient categorization in treatment protocol for PAH for those without cardiopulmonary comorbidites?
- Presence of right heart failure
- rapid progression of symptoms and clinical manifestations
- Repeated syncope
- WHO functional class IV
- 6 minute walk test less than 165 meters
- cardiopulmonary exercise testing with peak VO2 less than 11 mL/min/kg
- BNP greater than 800 ng/L
and more
What factors via the simplified 4-strata risk assessment tool qualifies a patient as high risk for PAH?
-WHO class IV
- 6 minute WT less than 165 meters
- BNP greater than 800 ng/L
- NT-proBNP greater than 1100 ng/L
What risk assessment tool is typically used in hospitals to determine level of risk associated with PAH?
REVEAL registry. This tool tells providers how aggressive treatment should be for PAH patients.
What are the 5 different PAH targets?
- Phosphodiesterase 5 (use PDE-5 inhibitors)
- Endothelin pathway (use endothelin receptor antagonists)
- Prostacyclin-cAMP pathway (use prostacyclin analogues or prostacyclin receptor agonists)
- Soluble guanylate cyclase (use soluble guanylate cyclase stimulators)
- Activin signaling inhibitors
What is the MOA of phosphodiesterase inhibitors?
PDE inhibitors stop the PDE isoenzyme from degrading cGMP. Increases in cGMP cause similar effects to nitric oxide including vasodilation, anti-proliferation, and antithrombotic effects.
What are the two phosphodiesterase inhibitors we need to know?
Sildenafil (Revatio) and Tadalafil (Adcirca)
What is the brand name for Sildenafil?
Revatio
What is the brand name for Tadalafil?
Adcirca
What is the dosing for Sildenafil (revatio) in PAH?
20 mg TID and may increase dose to 40mg TID
Sildenafil is _________ metabolised and therefore has many drug-drug interactions.
Hepatically
What is the dosing for Tadalafil for PAH?
40 mg daily
Which PDE-inhibitor is longer-acting, sildenafil or tadalafil?
Tadalafil
What are the 5 common side effects of phosphodiesterase inhibitors?
Flushing, dyspepsia, visual changes, epistaxis, and headaches
What is the most common side effect associated with phosphodiesterase inhibitors?
Headaches
T or F: In the majority of cases (exception for ICU admission), nitrates and phosphodiesterase inhibitors should never be used together.
True
What is Endothelin-1?
This is the predominant potent vasoconstrictor that promotes pulmonary arterial smooth muscle cell proliferation and disease progression. It binds to the Endothelin A receptors on smooth muscle cells to induce vasoconstriction and cellular proliferation. It binds to endothelin B receptors on endothelial cells to induce vasodilation and help clear endothelin 1.
What occurs when endothelin-1 binds to its endothelin-A receptor?
The endothelin A receptor is present on smooth muscle cells. Its activation induces vasoconstriction and cellular proliferation.
What occurs when endothelin-1 binds to its endothelin-B receptor?
The endothelin B receptor is present on endothelial cells. It activation induces vasodilation and clears endothelin-1.
Thinking about endothelin-1 receptors, A and B, which one is targeted in the treatment of PAH?
Endothelin-1 receptor antagonists target endothelin-A receptors. By antagonizing these receptors, vasoconstriction and cellular proliferation is stopped.
What are the 3 endothelin-1 receptor antagonist we need to know?
Bosentan (Tracleer), Ambrisentan (Letairis), and Macitentan (Opsumit)
T or F: Bosentan (Tracleer) is the most commonly used endothelin-1 receptor antagonist used in PAH.
False. This medication is almost never used anymore. It was the first of its kind on the market and is incredibly hepatotoxic.
In order to take Bosentan (Tracleer), patients must be enrolled in what program?
The Tracleer access program (TAP)
T or F: Ambrisentan (Letairis) is an endothelin receptor antagonist more selective for endothelin-B receptors.
False. This medication is more selective for the endothelin-A receptor (77:1)
What is the dosing for Ambrisentan (Letairis)?
5 mg daily (can be up to 10mg daily)
Strong ________ and ______ inhibitors can increase the serum concentration of Ambrisentan (Letairis)?
CYP2C19 and CYP3A4
What are the 4 common side effects associated with ambrisentan (Letairis)?
- Pulmonary edema
- decreased hemoglobin
- Serious birth defects if pregnant
- hepatoxticity
What is the most concerning side effect of Ambrisentan (Letairis)?
Pulmonary edema
How often does hemoglobin need to be monitored if a patient is on Ambrisentan (Letairis)?
At initiation, at 1 month on therapy, and then periodically after that
T or F: Be cautious of the use of Ambrisentan (Letairis) in those with liver dysfunction, hematological abnormalities, and peripheral edema.
True
In order for a patient to take Ambrisentan (Letairis), the patient must be enrolled in what program?
The Letairis Education and Access Program (LEAP). It requires the physician to enroll the patient, laboratory testing, signs of anemia, negative pregnancy test on initiation and every month, two acceptable forms of birth control, and a certified specialty pharmacy to give the patient the drug. The patient needs to be reenrolled after the first 6 months on the medication and annually after that.
What is the dosing for Macitentan (Opsumit) for PAH?
10 mg daily
T or F: Macitentan (Opsumit) reduces hospitalizations and delays disease progression in PAH.
True
What are the two black box warnings associated with Macitentan (Opsumit)?
Embryo-fetal toxicity and REMS programs for females only
Strong _______ and _______ inhibitors can increase the serum concentration of macitentan (Opsumit).
CYP2C19 and CYP3A4
What are the 4 adverse effects associated with Macitentan (Opsumit)?
- Headache
- decreased hemoglobin
- serious birth defects if taken while pregnant
- hepatotoxicity
T or F: Be cautious of the use of Macitentan (Opsumit) in those with liver dysfunction, hematological abnormalities, and peripheral edema.
True
In order for a female patients to receive Macitentan (Opsumit), they must be enrolled in what program?
REMS for Macitentan (Opsumit).
The physician enrolls only female patients and a negative pregnancy test is required on initiation and every month and they must be on two forms of birth control, and have a specialty pharmacy to receive the medication from.
T or F: Macitentan (Opsumit) can be crushed.
False
Prostacyclin targeted therapy use in PAH is only indicated for what WHO functional classes?
WHO functional class III and IV ONLY
Why are prostacyclins used as therapy in PAH?
In PAH, prostacyclins are low and low levels leads to vasoconstriction, thrombotic arteriopathy, proliferation, and fibrosis. We want to increase prostacyclins to combat this and increase vasodilation.
Prostacyclin therapy dosing is based on weight. Which weight is always used no matter what?
Initiation weight only and that weight is never altered for dosing. If a patient presents at 77kg but eventually weights 80kg in the hosptial, 77kg is still used to calculate prostacyclin dosing.
For patients on prostacyclin target therapy, what must they be educated on?
- complex delivery system of the medication
- sterile drug preparation techniques
- proper handling and storage of medication
- how the pump itself functions
- how to take care of the IV catheter
What are the 2 formulations in which prostacyclins are prepared as?
Oral or parenteral
What are the 4 prostacyclins that are used in PAH WHO functional class III or IV?
Treprostinil
Epopreostenol
Iloprost
Selexipeg
What is the brand name for the oral formulation of treprostinil?
Orenitram
What is the brand for the oral formulation of selexipeg?
Uptravi
What is the brand name for the IV and SubQ formulations of treprostinil?
Remodulin
What are the two brand names for the IV formulation of epopreostenol?
Flolan and Veletri
What is the brand name for the IV formulation of selexipeg?
Uptravi
What is the brand name for the inhaled formulation of treprostinil?
Tyvaso
What is the brand name for the inhaled formulation of Iloprost?
Ventavis
What is the only form that the prostacyclin Iloprost comes in?
Inhaled only
What is the only form that the prostacyclin epopreostenol comes in?
IV only
What are the 4 forms in which treprostinil comes in?
Oral, IV, SubQ, and inhaled
What are the two forms in which the prostacyclin selexipeg comes in?
Oral and IV
What type of pump is used within the hosptial setting to deliver prostacyclins to patients?
CADD-Solis pump
What was the first ever oral version of a prostacyclin for any disease including PAH?
Treprostinil oral (Orenitram)
What is the most common side effect associated with the oral prostacyclin Treprostinil (Orenitram)?
GI disturbances
Tolerability of the oral prostacyclin Treprostinil (Orenitram) is determined based off of what?
GI disturbances
What is the dosing for the oral prostacyclin Treprostinil (Orenitram)
BID with food or TID with food
Available in 0.125mg, 0.25mg, 1mg, and 2.5mg
Prostacyclin therapy is only indicated for WHO functional classes III and IV. The new inhaled prostacyclin Treprostinil (Tyvaso) is used is in which WHO pulmonary hypertension disease classification?
Group 1 (PAH) and group 3 (PHTN due to lung disease)
T or F: The inhaled prostacyclin, Treprostinil (Tyvaso), improved both the 6 minute walk test and quality of life in group 1 and 3 PHTN patients.
True
What are the 3 most common side effects associated with the inhaled prostacyclin, Treprostinil (tyvaso)?
Cough, headache, and throat irritation
What is the typical dosing for the inhaled prostacyclin, Treprostinil (tyvaso)?
Inhaled TX 4x per day
Why are there two different types of IV epopreostenol (Flolan and Veletri)?
The first one produced was Flolan and this medication was very unstable at room temperature. The new IV formulation of epoprostenol, Veletri, is stable at room temperature.
What is the half-life of the IV prostacyclin Epoprostenol (Veletri)?
Less than 6 minutes. This medication has a very quick on and off period. This medication is risky in the sense that interruption of cessation of the infusion can cause cardiovascular collapse.
What is the half-life of the IV and SubQ prostacyclin Treprostinil (Remodulin)?
Around 4.5 hours for both. This long half-life minimizes the risk for cardiovascular collapse if the infusion stops or gets interrupted.
IV administration of Treprostinil (Remodulin) requires what?
It requires long-term implantation of a central venous catheter.
T or F: The IV prostacyclin epoprostenol is more potent than the IV prostacyclin treprostinil (Remodulin).
True. Epoprostenol is more potent than treprostinil
What are the most common adverse effects seen with parenteral prostacyclins?
Minor decrease in blood pressure, flushing, headache, diarrhea, and jaw pain
Abrupt discontinuation of parenteral prostacyclins cause what two things to occur?
- Rebound pulmonary hypertension
- right ventricular failure
What monitoring needs to be done if patients are on parenteral prostacyclins?
Adverse effect management, dose titration, and the replacement supply at the hospital.
T or F: The inhaled prostacyclin, Illoprost (Ventavis), showed improved 6 minute walk tests as monotherapy and in combination with bosentan in those with WHO functional class III and IV.
True
What are the common side effects seen with the inhaled prostacyclin Illoprost (Ventavis)?
Cough, headache, flushing, and flu-like symptoms
How is the inhaled prostacyclin, Illoprost (ventavis), dosed?
6-9x per day (no more than once every 2 hours)
What is the one prostacyclin agonist, not analogue, used in PAH?
Selexipag (Uptravi)
What was the first medication for PAH (WHO group 1) that delayed disease progression and reduced the risk for hospitilizations?
The prostacyclin agonist, Selexipag (Uptravi)
What is the oral dosing for the prostacyclin agonist, Selexipeg (Uptravi)?
200 mcg BID
Increased by 200mcg BID at weekly intervals to the highest tolerated dose (max is 1600 mcg BID)
What are the most common side effects seen with the prostacyclin agonist, Selexipeg (Uptravi)?
Jaw pain, nausea, headache, vomiting, and flushing
T or F: Use caution with administration of Selexipeg (Uptravi) in those with renal impairments.
False. Caution use in those with hepatic impairments.
T or F: Oral selexipeg can be crushed for patients who have difficulty swallowing.
False. This medication cannot be crushed. The IV version must be used instead.
T or F: The IV to oral dosage for Selexipeg (Uptravi) is 1:1.
False. The dosing is similar but not exactly 1:1
How long is IV selexipeg good for use after being diluted?
4 hours including the time of the infusion. Must be protected from light as well.
What is the only soluble guanylate cyclase stimulator we need to know?
Riociguat (Adempas)
What is the MOA of soluble guanylate cyclase stimulator like Riociguat (Adempas)?
This medication sensitizes soluble guanylate cyclase (sGC) to endogenous nitric oxide by stabilizing the binding of nitric oxide to soluble guanylate cyclase. This leads to increased generation of cGMP and leads to vasodilation.
What is the only indicated use for soluble guanylate cyclase stimulator, Riociguat (Adempas)?
WHO group IV only (chronic thromboembolic pulmonary hypertension)
(may be used in WHO group I (PAH) but only if there is not response to PDE inhibitors)
What is the dosing for the soluble guanylate cyclase stimulator, Riociguat (Adempas)?
1 mg TID
Can start at 0.5mg TID in patients who do not tolerate the hypotensive effects well.
Max dose is 2.5 mg TID
What are the 4 main adverse effects of the soluble guanylate cyclase stimulator, Riociguat (Adempas)?
Hypotension, headache, dyspepsia, and anemia
What is the most common side effect associated with the soluble guanylate cyclase stimulator, Riociguat (Adempas)?
Headache
What is the only medication that is an activin signaling inhibitor?
Sotatercept
What is the MOA of activin signaling inhibitors like Sotatercept?
This is a homodimeric recombinant fusion protein that contains the extracellular domain of the human activin receptor type Ia. This extracellular portion links to the human IgG1 Fc domain and binds endogenous transforming growth factor beta superfamily ligands which results in the balance between pro-proliferative and anti-proliferative signaling to modulate vascular proliferation.
What is the indication for use of the activin signaling inhibitor, sotatercept?
Only indicated for WHO group 1 (PAH)
T or F: Sotatercept, an activin signaling inhibitor, increases exercise capacity, WHO functional class, and reduces the risk of clinical worsening in WHO class II PHTN.
False. It does all things things in WHO class I PAH, not WHO class II.
What is the dosing for sotatercept?
SubQ only
0.3mg/kg once weekly Q3weeks until target dose of 0.7mg/kg dose once weekly is reached and hemoglobin/platelet counts are stable
What needs to be monitored before and during patients receiving sotatercept?
Hemoglobin and platelet counts need to be monitored prior to each dose for the first 5 doses. This medication is not given is platelet count is less than 50,000.
T or F: Sotatercept along with other therapies showed an improved 6 minute walk test and reduced risk of death and clinical worsening in WHO class III PHTN patients.
False. Sotatercept showed these improvements in WHO class I (PAH), not WHO class III.
When is combination therapy used in the treatment of PAH?
Typically, combination therapy is used in patients who are newly diagnosed or in those with low or intermediate risk of death with their PAH.
What is one combination therapy discussed in class for PAH?
Macitentan/ Tadalafil combination
The combination therapy of Macitentan/ Tadalafil for PAH improved what?
It improved/reduced pulmonary vascular resistance in combination better than each agent alone.
If a patient presents with I/H/D PAH or PAH-CTD and has a negative vasoreactivity test. Additionally, this patient has no cardiopulmonary comorbidites and was found to have an intermediate risk of death due to his PAH. What medications should this patient be started on?
This patient needs to be initiated on ERA and PDE5-inhibitor therapy right away. This includes an endothelin receptor antagonist like Bosentan (Tracleer), Ambrisentan (Letairis), and Macitentan (Opsumit), and a PDE5-Inhibitor like sildenafil or tadalafil.
If a patient presents with I/H/D PAH or PAH-CTD and has a negative vasoreactivity test. Additionally, this patient has no cardiopulmonary comorbidites and was found to have an high risk of death due to his PAH. What medications should this patient be started on?
Initial 3 therapies including ERA and PDE5-inhibitor as well as IV or SubQ prostacyclins
If a patient presents with I/H/D PAH or PAH-CTD and has a negative vasoreactivity test. Additionally, this patient has no cardiopulmonary comorbidites and was found to have an intermediate risk of death due to his PAH. They were started on sildenafil and Ambrisentan (Letairis). Later on at a follow up appointment, the patient’s risk was calculated again via the 4-strata and was found to have intermediate risk still. What medications changes should be done?
In addition to the sildenafil and the Ambrisentan, the patient could be started on a prostacyclin or the PDE5i (sildenafil) could be switched to a sGC (soluble guanylate cyclase stimulator) like Riociguat (Adempas).
If a patient presents with I/H/D PAH or PAH-CTD and has a negative vasoreactivity test. Additionally, this patient has no cardiopulmonary comorbidites and was found to have an intermediate risk of death due to his PAH. They were started on sildenafil and Ambrisentan (Letairis). Later on at a follow up appointment, the patient’s risk was calculated again via the 4-strata and was found to have high risk. What medications changes should be done?
In addition to the sildenafil and ambrisentan, this patient needs to be initiated on IV or SubQ prostacyclins and be evaluated for a lung transplant.
What are the invasive treatment options for pulmonary arterial hypertension?
Atrioseptostomy with or without extracorporal membrane oxygenation (ECMO) or a transplant that is lung only or heart and lung.
What type of pulmonary arterial hypertensive patients is a lung transplant reserved for?
Patients whop continue to deteriorate with poor quality of life despite aggressive pharmacologic therapy.
Pulmonary hypertension is defined as a mean pulmonary arterial pressure greater than ________ mmHg.
20 mmHg
A patient with chronic thromboembolic pulmonary hypertension should receive __________.
A. Tadalafil
B. Bosentan
C. Treprostinil
D. Riociguat
D. Riociguat
T or F: A patient is receiving epoprostenol and loses 30 pounds. There dose should be adjusted based on their new weight.
False.
Which congenital heart defect is treated by administering NSAIDs to close the ductus arteriosus?
A. Coarctation of the aorta
B. Patent ductus arteriosus
C. Atrial septal defects
D. Ventricular septal defects
B. Patent ductus arteriosus
