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Related Concept Videos

Pulmonary Hypertension: Classification and Pathogenesis01:30

Pulmonary Hypertension: Classification and Pathogenesis

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Pulmonary hypertension (PH) is a severe health condition in which the mean pulmonary arterial pressure increases to 25 mmHg or more, even when the body is at rest. This high pressure in the blood vessels that transport blood from the heart to the lungs can cause various symptoms, including shortness of breath, can lead to right heart failure, and significantly affect the overall quality of life.
There are various classifications for PH, each relating to different underlying causes and also...
673
Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors01:28

Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors

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Phosphodiesterase 5 (PDE5) inhibitors are potent enzymes that function to hydrolyze cyclic nucleotides to their corresponding 5' monophosphates. Their unique biochemical properties have been applied in treating Pulmonary Arterial Hypertension (PAH).
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
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Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists01:18

Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists

489
Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
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Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists01:23

Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists

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Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
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Treatment for Pulmonary Arterial Hypertension: Oxygen Therapy for Respiratory Failure01:16

Treatment for Pulmonary Arterial Hypertension: Oxygen Therapy for Respiratory Failure

642
Oxygen therapy has emerged as a significant tool in enhancing the quality of life for patients suffering from pulmonary arterial hypertension (PAH). While this therapy has principally been studied on patients with significant hypoxemia, this therapeutic approach helps prevent potential organ damage and can be administered in the comfort of one's home.
Oxygen therapy is vital in increasing and maintaining blood oxygen levels in PAH patients. As a result, it aids in reducing fatigue,...
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Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

563
Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
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Evaluation of Right Ventricular Function in Experimental Models of Pulmonary Arterial Hypertension
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Evaluation of Right Ventricular Function in Experimental Models of Pulmonary Arterial Hypertension

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Macitentan in pulmonary hypertension due to left ventricular dysfunction.

Jean-Luc Vachiéry1, Marion Delcroix2, Hikmet Al-Hiti3

  • 1Dept of Cardiology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium jeanluc.vachiery@erasme.ulb.ac.be.

The European Respiratory Journal
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PubMed
Summary

Macitentan did not significantly improve outcomes for pulmonary hypertension with left heart disease (PH-LHD). Patients on macitentan were more likely to experience fluid retention, with no significant changes in other key health indicators.

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Area of Science:

  • Cardiology
  • Pulmonary Medicine
  • Clinical Trials

Background:

  • Pulmonary hypertension due to left heart disease (PH-LHD) presents complex therapeutic challenges.
  • Combined post- and pre-capillary PH in PH-LHD requires specific treatment considerations.
  • Evaluating novel therapies for PH-LHD is crucial for improving patient outcomes.

Purpose of the Study:

  • To assess the efficacy and safety of macitentan in treating patients with PH-LHD.
  • To determine macitentan's effect on fluid retention and functional class in PH-LHD patients.
  • To explore macitentan's impact on N-terminal pro-brain natriuretic peptide (NT-proBNP) and hemodynamic parameters.

Main Methods:

  • The MELODY-1 study was a randomized, placebo-controlled trial involving 63 patients with PH-LHD.
  • Participants received either macitentan 10 mg or a placebo for 12 weeks.
  • Primary endpoint: composite of significant fluid retention or worsening New York Heart Association functional class.

Main Results:

  • Macitentan did not significantly reduce the composite endpoint compared to placebo (10.08% difference, p=0.34).
  • Fluid retention was numerically higher in the macitentan group.
  • No significant changes were observed in pulmonary vascular resistance (PVR), right atrial pressure, or pulmonary arterial wedge pressure.

Conclusions:

  • Macitentan did not demonstrate significant efficacy in the primary endpoint for PH-LHD patients.
  • Increased fluid retention was observed in patients treated with macitentan.
  • Further research may be needed to identify effective treatments for PH-LHD.