Treatment Options For Pulmonary Hypertension Research Articles

Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure.

The first-in-class soluble guanylate cyclase (sGC) stimulator riociguat was recently introduced as a novel treatment option for pulmonary hypertension. Despite its outstanding pharmacological profile, application of riociguat in other cardiovascular indications is limited by its short half-life, necessitating a three times daily dosing regimen. In our efforts to further optimize the compound class, we have uncovered interesting structure-activity relationships and were able to decrease oxidative metabolism significantly. These studies resulting in the discovery of once daily sGC stimulator vericiguat (compound 24, BAY 1021189), currently in phase 3 trials for chronic heart failure, are now reported.

Treatment initiation in paediatric pulmonary hypertension: insights from a multinational registry.

Different treatment options for pulmonary hypertension have emerged in recent years, and evidence-based management strategies have improved quality of life and survival in adults. In children with pulmonary vascular disease, therapeutic algorithms are not so clearly defined; this study determined current treatment initiation in children with pulmonary hypertension in participating centres of a registry. Through the multinational Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension registry, patient demographics, diagnosis, and treatment as judged and executed by the local physician were collected. Inclusion criteria were >3 months and <18 years of age and diagnostic cardiac catheterisation consistent with pulmonary hypertension (mean pulmonary arterial pressure ⩾25 mmHg, pulmonary vascular resistance index ⩾3 Wood units×m2, and mean pulmonary capillary wedge pressure ⩽12 mmHg). At diagnostic catheterisation, 217/244 patients (88.9%) were treatment naïve for pulmonary hypertension-targeted therapy. Targeted therapy was initiated after catheterisation in 170 (78.3%) treatment-naïve patients. A total of 19 patients received supportive therapy, 28 patients were not started on therapy, and 26 patients (10.7%) were on targeted treatment before catheterisation. Among treatment-naïve subjects, treatment was initiated with one targeted drug (n=112, 51.6%), dual therapy (n=39, 18%) or triple-therapy (n=5, 2.3%), and calcium channel blockers with one targeted medication in one patient (0.5%). Phosphodiesterase inhibitors type 5 were used frequently; some patients with pulmonary hypertension related to lung disease received targeted therapy. There is a diverse therapeutic approach for children with pulmonary hypertension with a need of better-defined treatment algorithms based on paediatric consensus for different aetiologies including the best possible diagnostic workup.

Pulmonary hypertension complicating pulmonary sarcoidosis.

Pulmonary hypertension (PH) is a severe complication of sarcoidosis, with an unknown prevalence. The aetiology is multifactorial, and the exact mechanism of PH in the individual patient is often difficult to establish. The diagnostic work-up and treatment of PH in sarcoidosis is complex, and should therefore be determined by a multidisciplinary expert team in a specialised centre. It is still a major challenge to identify sarcoidosis patients at risk for developing PH. There is no validated algorithm when to refer a patient suspected for PH, and PH analysis itself is difficult. Until present, there is no established therapy for PH in sarcoidosis. Besides optimal treatment for sarcoidosis, case series evaluating new therapeutic options involving PH-targeted therapy are arising for a subgroup of patients. This review summarises the current knowledge regarding the aetiology, diagnosis and possible treatment options for PH in sarcoidosis.

Soluble Guanylate Cyclase Stimulators and Activators: Novel Therapies for Pulmonary Vascular Disease or a Different Method of Increasing cGMP?

Pulmonary arterial hypertension (PAH) is a progressively worsening disorder characterized by increased pulmonary vascular resistance leading to increased afterload, right ventricular hypertrophy, and ultimately right heart failure and death. Current pharmacologic treatments primarily act to reduce pulmonary vascular resistance (PVR) and provide some benefit but do not cure PAH. Canonical vasodilator therapy involving the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cGMP pathway has demonstrated efficacy, but in pathologic states, endothelial dysfunction within the pulmonary vasculature leads to the reduced synthesis and bioavailability of NO. Acting downstream of NO, sGC stimulators and activators restore the endogenous functions of NO and exploit the positive effects of sGC stimulation on various organ systems, including the heart. Riociguat (BAY 63-2521) is the first agent in a class of sGC stimulators to receive FDA approval for the treatment of PAH and chronic thromboembolic hypertension (CTEPH). Riociguat has demonstrated significant benefit as assessed by 6MWD, PVR, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, time to clinical worsening, World Health Organization (WHO) functional class, and other quality of life measures in clinical trials as a monotherapy and in combination with endothelin receptor antagonists or non-intravenous prostanoids. Riociguat is the first FDA-approved treatment option for inoperable or persistent CTEPH and adds a new effective drug to available treatment options for pulmonary hypertension (PH). The question of whether riociguat is superior to other available treatment options is unanswered at the present time and requires further study.

SELECTIVE ESTROGEN RECEPTOR AGONISTS ATTENUATE PULMONARY ARTERY VASOCONSTRICTION BY A NITRIC OXIDE-DEPENDENT MECHANISM

PURPOSE: Both endogenous and exogenous estrogen attenuates pulmonary artery (PA) vasoconstriction. Whether these effects are mediated via estrogen receptor (ER)-α or ER-β, remains unknown. A better understanding may result in novel, nonhormonal treatment options for pulmonary hypertension. We hypothesized that administration of the selective ER-α agonist propylpyrazole-triol (PPT) and/or the selective ER-β agonist diarylpropiolnitrile (DPN) attenuates PA vasoconstriction induced by pharmacologic and hypoxic stimuli.

Chronicling the Evolution of a Journal: We Welcome New Support to Meet Growing Educational Needs of Physicians

“Ten years ago physicians treating pulmonary hypertension would have been amazed at today’s options for managing a disease that had a dismal prognosis. Progress has been swift, and we stand at the threshold of a new era in treatment. As our treatment options for pulmonary hypertension have expanded dramatically, so has our need for more information to keep pace with major advances.”

Current Treatment For Pulmonary Hypertension

Pulmonary hypertension is a fatal disease. When left untreated, it progresses to death from right heart failure. Prostaglandins and their analogues are the mainstay of treatment. Intravenous Prostaglandins, Epoprostenol and Prostaglandins and their analogues are the mainstay of treatment. Intravenous Prostaglandins, Epoprostenol and calcium channel blockers are in use since many years. Several recent trials have established the efficacy of newer drugs. Trepostinil is a prostacyclin analogue which can be given as subcutaneous infusion. Iloprost is a prostaglandin analogue which can be given through intravenous as well as inhalational route. Beraprost can be used orally. Bosentan is a nonselective dual Endothelin receptor antagonist while Sitaxsentan is an oral selective Endothelin A receptor blocker. L Arginine , a precursor of Nitric Oxide can be used orally. Sildenafil, a phosphodiesterase inhibitor appears promising. Several options are now available for the treatment of pulmonary hypertension in addition to other adjunctive therapies. Present treatment options for pulmonary hypertension are discussed. However, further studies are required to evaluate the long-term efficacy of these drugs.

DA-8159, a new PDE5 inhibitor, attenuates the development of compensatory right ventricular hypertrophy in a rat model of pulmonary hypertension.

This study evaluated the effect of DA-8159, a new phosphodiesterase 5 inhibitor, on the compensatory development of right ventricular hypertrophy in monocrotaline (MCT)-induced pulmonary hypertension (PH). Rats treated with subcutaneous MCT were divided into three groups, which received DA-8159 1 mg/kg, DA-8159 5 mg/kg or saline-vehicle orally, twice daily for 21 days. The vehicle group demonstrated increased right ventricular weight, pulmonary artery medial wall thickening, myocardial fibrosis, increased plasma cyclic guanosine monophosphate (cGMP) concentration and reduced body weight gains. DA-8159, however, markedly attenuated the compensatory development of right ventricular hypertrophy and pulmonary artery medial wall thickening, amplified the increase in plasma cGMP levels and increased lung cGMP concentrations. In addition, DA-8159 prevented myocardial fibrosis induced by MCT. These results demonstrate that DA-8159 attenuates the compensatory development of right ventricular hypertrophy in a rate model of PH. DA-8159 might, therefore, be a useful treatment option for PH, but its efficacy in humans needs evaluating.

Management of pulmonary hypertension: physiological and pharmacological considerations for anesthesiologists.

For decades the pulmonary circulation was not considered as important as the systemic (“greater”) circulation. However, pulmonary hypertension can arise because of many diseases of the heart and lung. Therefore, increasing efforts in research have been undertaken leading to a profound increase in un

Medical and surgical treatment options for pulmonary hypertension.

Significant advances in the treatment of pulmonary hypertension have been achieved in the past decade. Approximately one quarter of patients with primary pulmonary hypertension (PPH) can be effectively managed with chronic calcium channel blocker therapy; for the remainder, transplantation or continuous intravenous epoprostenol are complex but effective approaches. Epoprostenol therapy was initially envisioned as a bridge to transplantation, but recent experience has established this approach as an alternative to transplantation in some patients, with comparable survival rates. Not all patients derive benefit from epoprostenol, however, and adverse effects are common. Accordingly, patients who fall into New York Heart Association Functional Classes III and IV and who are refractory to oral vasodilator therapy should be evaluated both for the initiation of epoprostenol therapy and concurrent listing for transplantation. By delaying or avoiding transplantation through the use of epoprostenol, these patients may also benefit from ongoing research that targets novel therapeutic approaches and less cumbersome delivery mechanisms. Thus, epoprostenol may serve as a bridge to transplantation for some patients and to newer therapeutic options for others.

Medical and Surgical Treatment Options for Pulmonary Hypertension

Significant advances in the treatment of pulmonary hypertension have been achieved in the past decade. Approximately one quarter of patients with primary pulmonary hypertension (PPH) can be effectively managed with chronic calcium channel blocker therapy; for the remainder, transplantation or continuous intravenous epoprostenol are complex but effective approaches. Epoprostenol therapy was initially envisioned as a bridge to transplantation, but recent experience has established this approach as an alternative to transplantation in some patients, with comparable survival rates. Not all patients derive benefit from epoprostenol, however, and adverse effects are common. Accordingly, patients who fall into New York Heart Association Functional Classes III and IV and who are refractory to oral vasodilator therapy should be evaluated both for the initiation of epoprostenol therapy and concurrent listing for transplantation. By delaying or avoiding transplantation through the use of epoprostenol, these patients may also benefit from ongoing research that targets novel therapeutic approaches and less cumbersome delivery mechanisms. Thus, epoprostenol may serve as a bridge to transplantation for some patients and to newer therapeutic options for others.