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The Heart of the Matter

Patients can present signs of progression in unique ways, and incomplete assessments can lead to an underestimation of mortality risk.1

Detrimental changes in right ventricular function can happen in as little as 12 weeks and occur before other indicators of progression, such as FC and 6MWD. They are also the first warning sign on the path to potential hospitalization.2,3

LEADING INDICATOR

Right ventricular function

LAGGING INDICATORS

Functional class and 6-minute walk distance

RV changes occur before other indicators of progression.3

Right ventricular function and PAH disease progression

Perform clinical assessments at 3- and 6-month intervals.4

Recent data have indicated that PAH-related hospitalizations are associated with adverse clinical outcomes, which refers to mortality, all-cause hospitalization, and readmission for PAH disease progression. Yet, in a clinical study examining treatment patterns, most patients had no therapy modification within 90 days of hospitalization.5

Learn more about the importance of prioritizing early results and acting in a timely manner to help improve long-term prognosis.

ECHOCARDIOGRAMS CAN HELP IDENTIFY WHEN PATIENTS ARE NOT AT LOW RISK, DESPITE IMPROVEMENTS6

Relying on subjective judgment of physical activity level or lagging indicators of disease progression, such as FC and 6MWD, over a leading indicator like RV function can lead to an underestimation of risk status. Guidelines recommend echocardiography and right heart catheterization at least every 6 months and as early as 3 months after a change in therapy, with an overall treatment goal of achieving low-risk status.1,3,6

Echocardiograms can help you assess your patient's RV function noninvasively and may help you identify a worsening prognosis.7 This is true even if parameters such as FC and 6MWD show signs of improvement.8

See the hypothetical patient case below for an example of how an echocardiogram can help determine the next treatment steps for a patient.

47-Year-Old Female With PAH

Baseline (Diagnosis)

Abbreviated ESC/ERS risk score of 2.2 (intermediate risk)*
  • NT-proBNP 813 ng/L
Echo findings consistent with intermediate risk:
  • Right ventricular hypertrophy with RV/LV ratio >1.0
  • RA area 21 cm2
  • TAPSE 1.6 cm (Doppler echo)
  • Peak TRV 3.2 m/s (Doppler echo)

Based on the patient’s risk score and echo findings, patient was initiated on upfront dual combination therapy per WSPH guidelines.

4 Months After Upfront Combination Therapy

Abbreviated ESC/ERS risk score improved to 1.9 (intermediate risk)*
  • NT-proBNP 675 ng/L
Echo findings show improvement, but evidence of RV dysfunction remains:
  • RV/LV ratio >1.0
  • RA area 19 cm2
  • TAPSE 1.9 cm (Doppler echo)
  • Peak TRV 3.0 m/s (Doppler echo)

Although RV appears to have improved, function has not reached near-normal levels and the patient is still not at low risk.

Echo Parameters For Worsening Prognosis9

RV/LV ratio >0.93
RA area >18 cm2
TAPSE <1.8 cm
Peak TRV >2.8 m/s

*Based on a comprehensive assessment including clinical features, WHO FC, 6MWD, CPET, BNP, NT-proBNP, and certain variables derived from echocardiography and right heart catheterization.10

See how a closer look at the intermediate-risk population can better inform treatment decisions based on risk status.

6MWD=6-minute walk distance; BNP=B-type natriuretic peptide; CPET=cardiopulmonary exercise testing; ERS=European Respiratory Society; ESC=European Society of Cardiology; FC=functional class; LV=left ventricle; NT-proBNP=N-terminal pro–B-type natriuretic peptide; PAH=pulmonary arterial hypertension; RA=right atrial; RV=right ventricle/right ventricular; TAPSE=tricuspid annular plane systolic excursion; TRV=tricuspid regurgitation velocity; WHO=World Health Organization; WSPH=World Symposium on Pulmonary Hypertension.

Important Safety Information

Warnings and Precautions

  • Chronic intravenous (IV) infusions of Remodulin delivered using an external infusion pump with an indwelling central venous catheter are associated with the risk of blood stream infections (BSIs) and sepsis, which may be fatal. Therefore, continuous subcutaneous (SC) infusion is the preferred mode of administration.
  • Avoid abrupt withdrawal or sudden large reductions in dosage of Remodulin, which may result in worsening of PAH symptoms.
  • Titrate slowly in patients with hepatic or renal insufficiency, because such patients will likely be exposed to greater systemic concentrations relative to patients with normal hepatic or renal function.
  • Remodulin is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, treatment with Remodulin may produce symptomatic hypotension.
  • Remodulin inhibits platelet aggregation and increases the risk of bleeding.

Adverse Reactions

  • In clinical studies of SC Remodulin infusion, the most common adverse events reported were infusion site pain and infusion site reaction (redness, swelling, and rash). These symptoms were sometimes severe and sometimes required treatment with narcotics or discontinuation of Remodulin. The IV infusion of Remodulin with an external infusion pump has been associated with a risk of blood stream infections, arm swelling, paresthesias, hematoma, and pain. Other common adverse events (≥3% more than placebo) seen with either SC or IV Remodulin were headache (27% vs. 23%), diarrhea (25% vs. 16%), nausea (22% vs. 18%), rash (14% vs. 11%), jaw pain (13% vs. 5%), vasodilatation (11% vs. 5%), edema (9% vs. 3%), and hypotension (4% vs. 2%).

Drug Interactions

  • Remodulin dosage adjustment may be necessary if inhibitors or inducers of CYP2C8 are added or withdrawn.

Specific Populations

  • In patients with mild or moderate hepatic insufficiency, decrease the initial dose of Remodulin to 0.625 ng/kg/min of ideal body weight, and monitor closely. Remodulin has not been studied in patients with severe hepatic insufficiency.
  • Safety and effectiveness of Remodulin in pediatric patients have not been established.
  • It is unknown if geriatric patients respond differently than younger patients. Caution should be used when selecting a dose for geriatric patients.
  • There are no adequate and well-controlled studies with Remodulin in pregnant women. It is not known whether treprostinil is excreted in human milk or if it affects the breastfed infant or milk production.

Indication

Remodulin is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise. Studies establishing effectiveness included patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (58%), PAH associated with congenital systemic-to-pulmonary shunts (23%), or PAH associated with connective tissue diseases (19%).

In patients with PAH requiring transition from epoprostenol, Remodulin is indicated to diminish the rate of clinical deterioration. Consider the risks and benefits of each drug prior to transition.

REMISIhcpMAY2021

Please see accompanying Full Prescribing Information for Remodulin.

For additional information, visit www.RemodulinPro.com or call Customer Service at 1-877-UNITHER (1-877-864-8437).

Important Safety Information

Warnings and Precautions

  • Chronic intravenous (IV) infusions of Remodulin delivered using an external infusion pump with an indwelling central venous catheter are associated with the risk of blood stream infections (BSIs) and sepsis, which may be fatal. Therefore, continuous subcutaneous (SC) infusion is the preferred mode of administration.
  • Avoid abrupt withdrawal or sudden large reductions in dosage of Remodulin, which may result in worsening of PAH symptoms.
  • Titrate slowly in patients with hepatic or renal insufficiency, because such patients will likely be exposed to greater systemic concentrations relative to patients with normal hepatic or renal function.
  • Remodulin is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, treatment with Remodulin may produce symptomatic hypotension.
  • Remodulin inhibits platelet aggregation and increases the risk of bleeding.

Adverse Reactions

  • In clinical studies of SC Remodulin infusion, the most common adverse events reported were infusion site pain and infusion site reaction (redness, swelling, and rash). These symptoms were sometimes severe and sometimes required treatment with narcotics or discontinuation of Remodulin. The IV infusion of Remodulin with an external infusion pump has been associated with a risk of blood stream infections, arm swelling, paresthesias, hematoma, and pain. Other common adverse events (≥3% more than placebo) seen with either SC or IV Remodulin were headache (27% vs. 23%), diarrhea (25% vs. 16%), nausea (22% vs. 18%), rash (14% vs. 11%), jaw pain (13% vs. 5%), vasodilatation (11% vs. 5%), edema (9% vs. 3%), and hypotension (4% vs. 2%).

Drug Interactions

  • Remodulin dosage adjustment may be necessary if inhibitors or inducers of CYP2C8 are added or withdrawn.

Specific Populations

  • In patients with mild or moderate hepatic insufficiency, decrease the initial dose of Remodulin to 0.625 ng/kg/min of ideal body weight, and monitor closely. Remodulin has not been studied in patients with severe hepatic insufficiency.
  • Safety and effectiveness of Remodulin in pediatric patients have not been established.
  • It is unknown if geriatric patients respond differently than younger patients. Caution should be used when selecting a dose for geriatric patients.
  • There are no adequate and well-controlled studies with Remodulin in pregnant women. It is not known whether treprostinil is excreted in human milk or if it affects the breastfed infant or milk production.

Indication

Remodulin is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise. Studies establishing effectiveness included patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (58%), PAH associated with congenital systemic-to-pulmonary shunts (23%), or PAH associated with connective tissue diseases (19%).

In patients with PAH requiring transition from epoprostenol, Remodulin is indicated to diminish the rate of clinical deterioration. Consider the risks and benefits of each drug prior to transition.

REMISIhcpMAY2021

Please see accompanying Full Prescribing Information for Remodulin.

For additional information, visit www.RemodulinPro.com or call Customer Service at 1-877-UNITHER (1-877-864-8437).

References: 1. Sahay S, Tonelli AR, Selej M, et al. Risk assessment in patients with functional class II pulmonary arterial hypertension: comparison of physician gestalt with ESC/ERS and the REVEAL 2.0 risk score. PLoS One. 2020;15(11):e0241504. doi:10.1371/journal.pone.0241504. 2. Simonneau G, Barst RJ, Galie N, et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2002;165(6):800-804. 3. Milks MW, Sahay S, Benza RL, et al. Risk assessment in patients with pulmonary arterial hypertension in the era of COVID 19 pandemic and the telehealth revolution: state of the art review. J Heart Lung Transplant. 2021;40(3):172-182. 4. Cascino TM, McLaughlin VV. Upfront combination therapy for pulmonary arterial hypertension: time to be more ambitious than AMBITION. Am J Respir Crit Care Med. 2021;204(7):756-759. 5. Ogbomo A, Tsang Y, Kariburyo F, et al. Real-world analysis of treatment patterns among hospitalized patients with pulmonary arterial hypertension. Pulm Ther. 2021;7(2):575-590. 6. Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). Eur Respir J. 2015;46(4):903-975. 7. Truong U, Meinel K, Haddad F, et al. Update on noninvasive imaging of right ventricle dysfunction in pulmonary hypertension. Cardiovasc Diagn Ther. 2020;10(5):1604-1624. 8. van de Veerdonk MC, Marcus JT, Westerhof N, et al. Signs of right ventricular deterioration in clinically stable patients with pulmonary arterial hypertension. Chest. 2015;147(4):1063-1071. 9. Brugger N, Lichtblau M, Maeder M, et al. Two-dimensional transthoracic echocardiography at rest for the diagnosis, screening and management of pulmonary hypertension. Swiss Med Wkly. 2021;151:w20486. doi:10.4414/smw.2021.20486. 10. Hoeper MM, Kramer T, Pan Z, et al. Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J. 2017;50(2):1700740. doi:10.1183/13993003.00740-2017.