Abstract:BackgroundPulmonary hypertension (PH) due to left heart failure (HF) is the most common form of PH. However, treatment is unclear because there are conflicting results about safety and efficacy of PH-targeted therapies.ObjectivesTo assess the effects of PH-targeted therapy on exercise capacity in HF patients.MethodsMEDLINE, EMBASE and the Cochrane Library were searched from January 1990 to July 2017 for randomized controlled trials comparing PH-targeted therapies to conventional therapy in HF. The primary outc… Show more
“…An exploratory analysis suggested PDE5i may be associated with a decrease in cardiac hospitalizations in some patients with HF but not in patients with valvular disease. 29 These findings are consistent with our study despite differences in patient population (echo diagnosis of PH and inclusion of VHD with no mention of PVR in their SR). The authors also reported a significant increase in treatment discontinuation, with no mention in the subgroup population taking PDE5i.…”
Pulmonary Hypertension due to left heart disease is the most common type of Pulmonary Hypertension. Morbidity and mortality significantly increase once Pulmonary Hypertension is present. Treatment is aimed toward optimizing the underlying condition. Targeted therapy has been evaluated in small studies with mixed results. The goal of this systematic review is to identify the possible benefit and safety of Phosphodiesterase 5 inhibitors in Pulmonary Hypertension due to left heart disease with elevated pulmonary vascular resistance, diagnosed by right heart catheterization. Electronic searches using MEDLINE/PREMEDLINE, EMBASE, and The Cochrane Library were searched on 21 October 2018. Randomized clinical trials comparing Phosphodiesterase 5 inhibitors versus placebo in patients with proven Pulmonary Hypertension by right heart catheterization secondary to left heart disease (both heart failure with reduced ejection fraction and with preserved ejection fraction) and reported pulmonary vascular resistance were included. We identified 436 potentially relevant studies. After reviewing the titles and abstracts to exclude irrelevant articles, five randomized clinical trials were considered for the study. Sildenafil was well tolerated among all studies. Sildenafil was found to improve hemodynamics, exercise capacity, and quality of life in patients with elevated pulmonary vascular resistance. Phosphodiesterase 5 inhibitors therapy in patients with proven Pulmonary Hypertension due to left heart disease and elevated pulmonary vascular resistance by right heart catheterization may improve the quality of life, exercise capacity, and pulmonary hemodynamics. Further prospective randomized controlled studies are needed to confirm.
“…An exploratory analysis suggested PDE5i may be associated with a decrease in cardiac hospitalizations in some patients with HF but not in patients with valvular disease. 29 These findings are consistent with our study despite differences in patient population (echo diagnosis of PH and inclusion of VHD with no mention of PVR in their SR). The authors also reported a significant increase in treatment discontinuation, with no mention in the subgroup population taking PDE5i.…”
Pulmonary Hypertension due to left heart disease is the most common type of Pulmonary Hypertension. Morbidity and mortality significantly increase once Pulmonary Hypertension is present. Treatment is aimed toward optimizing the underlying condition. Targeted therapy has been evaluated in small studies with mixed results. The goal of this systematic review is to identify the possible benefit and safety of Phosphodiesterase 5 inhibitors in Pulmonary Hypertension due to left heart disease with elevated pulmonary vascular resistance, diagnosed by right heart catheterization. Electronic searches using MEDLINE/PREMEDLINE, EMBASE, and The Cochrane Library were searched on 21 October 2018. Randomized clinical trials comparing Phosphodiesterase 5 inhibitors versus placebo in patients with proven Pulmonary Hypertension by right heart catheterization secondary to left heart disease (both heart failure with reduced ejection fraction and with preserved ejection fraction) and reported pulmonary vascular resistance were included. We identified 436 potentially relevant studies. After reviewing the titles and abstracts to exclude irrelevant articles, five randomized clinical trials were considered for the study. Sildenafil was well tolerated among all studies. Sildenafil was found to improve hemodynamics, exercise capacity, and quality of life in patients with elevated pulmonary vascular resistance. Phosphodiesterase 5 inhibitors therapy in patients with proven Pulmonary Hypertension due to left heart disease and elevated pulmonary vascular resistance by right heart catheterization may improve the quality of life, exercise capacity, and pulmonary hemodynamics. Further prospective randomized controlled studies are needed to confirm.
“… 87 A meta‐analysis pooling the results of multiple PH‐targeted therapies such as PDE5 inhibitors, prostanoids, ERAs, and soluble guanylate cyclase stimulators has concluded that PDE5 inhibitors may improve exercise capacity in patients with LHD, but that all drug classes resulted in a higher risk for adverse events. 88 …”
Pulmonary hypertension (PH) attributable to left heart disease (LHD) is believed to be the most common form of PH and is strongly associated with increased mortality and morbidity in this patient population. Specific therapies for PH‐LHD have not yet been identified and the use of pulmonary artery hypertension‐targeted therapies in PH‐LHD are not recommended. Endothelin receptor antagonists, phosphodiesterase‐5 inhibitors, guanylate cyclase stimulators, and prostacyclins have all been studied in PH‐LHD with conflicting results. Understanding the mechanisms underlying PH‐LHD could potentially provide novel therapeutic targets. Fibrosis, oxidative stress, and metabolic syndrome have been proposed as pathophysiological components of PH‐LHD. Genetic associations have also been identified, offering additional mechanisms with biological plausibility. This review summarizes the evidence and challenges for treatment of PH‐LHD and focuses on underlying mechanisms on the horizon that could develop into potential therapeutic targets for this disease.
“…In a small minority of IPAH patients who are deemed vasoreactive based on a positive acute vasodilator challenge and without severe RV dysfunction, calcium channel blockers are appropriate and safe to use in pregnancy [3•]. Importantly, PAH-targeted agents have not been shown to be of benefit and can be detrimental in PH due to left heart disease [69]. Therapy in this group should be directed toward optimization of left heart function.…”
Purpose of review
This study aims to describe the pathophysiology of pregnancy in pulmonary hypertension (PH) and review recent literature on maternal and fetal outcomes.
Recent findings
There is an increasing number of pregnant women with PH. Maternal mortality in pulmonary arterial hypertension (PAH) ranges from 9 to 25%, most commonly from heart failure and arrythmias. The highest risk of death is peri-partum and post-partum. Fetal/neonatal morbidity and mortality are also substantial. There are high rates of prematurity, intrauterine growth retardation, and preeclampsia. Women should be referred to expert centers for management. Combination PAH therapy with parenteral prostacyclin and a phosphodiesterase type V inhibitor is recommended. Induced vaginal delivery is preferred, except in cases of severe heart failure or obstetric indications for cesarean section.
Summary
Despite advances in management, pregnancy in PAH remains a high-risk condition and should be prevented.
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