Long-term Inhaled Nitric Oxide Plus Phosphodiesterase 5 Inhibitors for Severe Pulmonary Hypertension

Pérez-Peñate, Gregorio; Juliá-Serdà, Gabriel; Ojeda-Betancort, Nazario; García-Quintana, Antonio; Pulido-Duque, J. M.; Rodríguez‐Pérez, Aurelio; Cabrera-Navarro, Pedro; Gómez-Sánchez, Miguel Ángel

doi:10.1016/j.healun.2008.08.007

Cited by 18 publications

(29 citation statements)

References 25 publications

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“…Previous studies have shown that it is possible to administer NO to an awake patient via a facemask or nasal cannula. [35][36][37][38] However, it would be vital to demonstrate that the delivered dose and any nitrogen dioxide build up could be accurately monitored. An alternative approach is a noninhalational vasodilator (ie, prostacyclin), which should induce changes in septal curvature, as deformation is primarily a mechanical process.…”

Section: Discussionmentioning

confidence: 99%

Real-Time Magnetic Resonance Assessment of Septal Curvature Accurately Tracks Acute Hemodynamic Changes in Pediatric Pulmonary Hypertension

Pandya

Quail

Steeden

et al. 2014

Circ: Cardiovascular Imaging

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Background-This study assesses the relationship between septal curvature and mean pulmonary artery pressure and indexed pulmonary vascular resistance in children with pulmonary hypertension. We hypothesized that septal curvature could be used to estimate right ventricular afterload and track acute changes in pulmonary hemodynamics. Methods and Results-Fifty patients with a median age of 6.7 years (range, 0.45-16.5 years) underwent combined cardiac catheterization and cardiovascular magnetic resonance. The majority had idiopathic pulmonary arterial hypertension (n=30); the remaining patients had pulmonary hypertension associated with repaired congenital heart disease (n=17) or lung disease (n=3). Mean pulmonary artery pressure and pulmonary vascular resistance were acquired at baseline and during vasodilation. Septal curvature was measured using real-time cardiovascular magnetic resonance. There was a strong correlation between mean pulmonary artery pressure and SC min at baseline and during vasodilator testing (r=-0.81 and -0.85, respectively; P<0.01). A strong linear relationship also existed between pulmonary vascular resistance and minimum septal curvature indexed to cardiac output both at baseline and during vasodilator testing (r=-0.88 and -0.87, respectively; P<0.01). Change in septal curvature metrics moderately correlated with absolute change in mean pulmonary artery pressure and pulmonary vascular resistance, respectively (r=0.58 and -0.74; P<0.01). Septal curvature metrics were able to identify vasoresponders with a sensitivity of 83% (95% confidence interval, 0.36-0.99) and a specificity of 91% (95% confidence interval, 0.77-0.97), using the Sitbon criteria. Idiopathic pulmonary arterial hypertension subgroup analysis revealed 3 responders with ΔSC min values of 0.523, 0.551, and 0.568. If the middle value of 0.551 is taken as a cutoff, the approximate sensitivity would be 67% and the specificity would be 93%. Conclusions-Septal curvature metrics are able to estimate right ventricular afterload and track acute changes in pulmonary hemodynamics during vasodilator testing. This suggests that septal curvature could be used for continuing assessment of load in pulmonary hypertension. (Circ Cardiovasc Imaging. 2014;7:706-713.)

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Section: Discussionmentioning

confidence: 99%

Real-Time Magnetic Resonance Assessment of Septal Curvature Accurately Tracks Acute Hemodynamic Changes in Pediatric Pulmonary Hypertension

Pandya

Quail

Steeden

et al. 2014

Circ: Cardiovascular Imaging

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“…Although chronic iNO therapy for PAH is feasible92, delivery is complicated by the instability of NO, which mandates continuous inhalation. In addition, higher concentrations of NO and especially its oxidation products are toxic.…”

Section: Nonoatesmentioning

confidence: 99%

Basic Science of Pulmonary Arterial Hypertension for Clinicians

Weir²,

2010

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P ulmonary arterial hypertension (PAH) is a syndrome in which pulmonary arterial obstruction increases pulmonary vascular resistance, which leads to right ventricular (RV) failure and a 15% annual mortality rate. The present review highlights recent advances in the basic science of PAH. New concepts clarify the nature of PAH and provide molecular blueprints that explain how PAH is initiated and maintained. Five basic science concepts provide a framework to understand and treat PAH: (1) Endothelial dysfunction creates an imbalance that favors vasoconstriction, thrombosis, and mitogenesis. Restoration of this balance by inhibition of endothelin and thromboxane or augmentation of nitric oxide (NO) and prostacyclin is the paradigm on which most current therapy is based. (2) PAH has a genetic component. Mutations (bone morphogenetic protein receptor-2 [BMPR2]) and single-nucleotide polymorphisms (SNPs; ion channels and transporter genes) predispose to PAH. (3) Excess proliferation, impaired apoptosis, and glycolytic metabolism in pulmonary artery smooth muscle, fibroblasts, and endothelial cells suggest analogies to cancer. Many experimental therapies reduce PAH by decreasing the proliferation/apoptosis ratio; these include inhibitors of pyruvate dehydrogenase kinase (PDK), serotonin transporters (SERT), survivin, 3-hydroxy-3-methylglutaryl coenzyme A reductase, transcription factors (hypoxia-inducible factor [HIF]-1␣ and nuclear factor of activated T lymphocytes [NFAT]), and tyrosine kinases. Augmentation of voltage-gated K ϩ channels (Kv1.5) and BMPR2 signaling also addresses this imbalance. Tyrosine kinase inhibitors used to treat cancer are currently in phase 1 PAH trials. (4) Refractory vasoconstriction may occur due to rho kinase activation. Fewer than 20% of PAH patients respond to conventional vasodilators; however, refractory vasoconstriction may respond to rho kinase inhibitors. (5) The RV can be targeted therapeutically. Although increased afterload initiates RV failure, which is the major cause of death/dysfunction in PAH, the RV may be amenable to cardiac-targeted therapies. The RV in PAH has features of ischemic, hibernating myocardium.Guided by these new concepts and armed with a better understanding of disease mechanisms, we are poised to identify new therapeutic targets. To achieve balance in a rapidly evolving field, we invited colleagues to contribute Figures and legends illustrating pathways in their area of expertise that are important to the pathogenesis and treatment of PAH. These contributors are acknowledged in the Acknowledgments section.

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“…However, no specific data on the benefits of bosentan monotherapy versus combination therapy were provided. A small case series (171) reported improved pulmonary hemodynamics over one year following addition of oral dipyridamole or sildenafil in three patients with severe inoperable CTEPH (WHO class III or IV) who were clinically deteriorating despite therapy with inhaled nitric oxide for one year (171). Presently, these combinations of medical therapies are not often clinically used or available, and the specific benefits of combination versus monotherapy have not been rigorously assessed.…”

Section: Combination Ph-specific Medical Therapy In Cteph Patientsmentioning

confidence: 99%

Diagnostic Evaluation and Management of Chronic Thromboembolic Pulmonary Hypertension: A Clinical Practice Guideline

Mehta

Helmersen

Provencher

et al. 2010

Canadian Respiratory Journal

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Long-term Inhaled Nitric Oxide Plus Phosphodiesterase 5 Inhibitors for Severe Pulmonary Hypertension

Cited by 18 publications

References 25 publications

Real-Time Magnetic Resonance Assessment of Septal Curvature Accurately Tracks Acute Hemodynamic Changes in Pediatric Pulmonary Hypertension

Real-Time Magnetic Resonance Assessment of Septal Curvature Accurately Tracks Acute Hemodynamic Changes in Pediatric Pulmonary Hypertension

Basic Science of Pulmonary Arterial Hypertension for Clinicians

Diagnostic Evaluation and Management of Chronic Thromboembolic Pulmonary Hypertension: A Clinical Practice Guideline

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