Use Of Sildenafil Research Articles

Precautions and Monitoring of Patients Taking Phosphodiesterase Type 5 Inhibitors Who are at Risk of Increased Intraocular Pressure.

Phosphodiesterase type 5 inhibitors (PDE5Is) may increase intraocular pressure (IOP) by increasing blood flow to the ciliary body. Although clinical studies of changes in IOP after single and multiple doses of PDE5Is show variable results, most are limited by small sample sizes, absence of control groups and blinding, and use of normal patient volunteers who have no risk factors for glaucoma. However, multiple case reports of glaucoma have been published, and one epidemiologic analysis of the National Health and Nutrition Examination Survey (NHANES) database of US respondents suggested a significant association of prolonged sildenafil use and self-reported glaucoma. With the widespread use of PDE5Is for treatment of erectile dysfunction in males with risk factors for glaucoma, and the potential of PDE5Is to worsen optic nerve damage in patients with glaucoma, we recommend a vision screening exam prior to the initiation of the PDE5I and careful follow-up thereafter, particularly if the patient is taking tadalafil, a long-acting PDE5I, if the patient is taking high doses of a PDE5I daily and persistently, and if the patient has risk factors for glaucoma or if the patient is at risk of worsening glaucoma.

Sildenafil (Viagra) as a Possible Culprit for Vision Loss

Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) is the most common clinical presentation of acute ischemic damage to the optic nerve. In this case report, we are presenting a patient with bilateral sequential NAION who had a history of blood clothing disorders and found to have NAION in the second eye immediately after use of Sildenafil for erectile dysfunction.

Sildenafil citrate adjuvant treatment in women with polycystic ovary syndrome following clomiphene failure: A randomized controlled trial

Objective: The widespread classic PCOS treatment algorithm, consisting of 6-12 cycles of clomiphene followed by shifting to gonadotropins in case of failure to conceive, doesn’t really address the cause of failure to conceive despite documented ovulation. Sildenafil citrate improves uterine blood flow, enhances endometrial development and modulates endometrial receptivity. Hence, this study monitored the ovarian response, endometrial development and subendometrial Doppler changes in PCOS women with previous clomiphene citrate failure following the use of adjuvant sildenafil citrate instead of shifting to gonadotropins. Patients and Methods: A double-blinded randomized controlled trial was conducted in Ain-Shams University Women’s Hospital on 850 PCOS women with clomiphene failure. Those were randomized to clomiphene therapy, either with adjuvant placebo or sildenafil citrate (25 mg orally 6 hourly), starting from the 6th day till the end of the cycle.Folliculometry, every other day, started on the 10th day of the cycle. When ≥1 follicle reached a size ≥18mm, transvaginal ultrasound assessment of the endometrium and uterine/subendometrial Doppler was done. The resulting pregnancy rates were recorded. Results: The sildenafil group developed higher endometrial thickness (10.6±1.3 versus 9.4±1.5; p<0.001), a higher percentage of women with trilaminar endometrium (78.35% versus 59.76%; p<0.001) was found while the lower percentage was found with subendometrial and uterine artery Doppler indices (p<0.001 for all). It also developed higher pregnancy rates (43.7% versus 34.5%, p=0.006; NNT=10.8, 95% CI: 6.36 – 37.84).Conclusion: Sildenafil adjuvant therapy significantly increased pregnancy rates, improved endometrial development in terms of endometrial thickness and pattern as well as uterine and subendometrial blood flow.

The effects of sildenafil in maternal and fetal outcomes in pregnancy: A systematic review and meta-analysis.

BackgroundThe number of studies associating the use of sildenafil in gestation is increasing. This drug inhibits phosphodiesterase type 5 (PDE5), an enzyme responsible for degradation of nitric oxide, and its efficacy is greater in the placental territory, as the maternal side of the placenta have more PDE5 than other sites. For this reason, promising results have been observed related to the prevention of preeclampsia and intrauterine growth restriction and to improvement of maternal-fetal morbidity in cases of placental insufficiency.ObjectiveTo evaluate the benefits of using sildenafil in pregnancy.Searched strategyMEDLINE, ClinicalTrials.gov, Embase, LILACS and Cochrane databases were searched through September 2018. There was no restriction in language or year of publication. This study was registered in PROSPERO (CRD42017060288).Selection criteriaRandomized clinical trials which used sildenafil for treatment or prevention of obstetric diseases compared with placebo were selected.Data collection and analysisThe results were obtained using the inverse variance method for continuous variables and Man-Whitney for categorical variables.Main resultsAmong a population of 598 pregnant women from the seven clinical trials included, 139 had pre-eclampsia, 275 had intrauterine growth restriction, and 184 had oligohydramnios. A significant increase of 222.58 grams [27.75 to 417.41] was observed in the fetal weight at birth of patients taking sildenafil. The other outcomes did not show any statistical significance. This may be due to the small number of patients used in each study and the great heterogeneity between the groups.ConclusionsSildenafil could be associated with increasing fetal weight at birth in placental insufficiency despite the limitations of this meta-analysis, even though more studies in this field are needed to introduce this drug into obstetric clinical practice.

EXPRESS: Sildenafil for bronchopulmonary dysplasia and pulmonary hypertension: a meta-analysis.

Bronchopulmonary dysplasia (BPD) is the most common complication in preterm infants and often complicated by pulmonary hypertension (PH), leading to substantial morbidity and mortality. Sildenafil is often used to treat PH and improve symptoms in this condition, even though evidence of safety and effectiveness is scarce. The aim of this study was to perform a systematic review and meta-analysis about the effectiveness and safety of chronic use of sildenafil in preterm infants with BPD-associated PH. Data sources were PubMed, EMBASE, and Medline. Studies reporting the effectiveness of sildenafil therapy in BPD-associated PH in newborns and infants were included. All-cause mortality, improvement in PH, improvement in respiratory scores, and adverse events were extracted. Five studies were included, yielding a total of 101 patients with 94.2 patient-years of total follow-up. The pooled mortality rate was 29.7%/year (95% confidence interval [CI] = 6.8–52.7). Estimated pulmonary arterial pressure improved > 20% in 69.3% (95% CI = 56.8–81.8) of patients within 1–6 months. Respiratory scores improved in 15.0% (95% CI = 0.0–30.4) of patients within 2–7 days. There were no serious adverse events during sildenafil therapy. This systematic review shows that in the treatment of BPD-associated PH in preterm infants, sildenafil may be associated with improvement in PAP and respiratory scores. However, there is no clear evidence of its effect on mortality rates. Considering BPD as a complex disease with variable expression patterns, these results support the need for a prospective registry and standardized approach.

Health Technology Assessment on Sildenafil as Treatment of Pulmonary Arterial Hypertension

Sildenafil is a treatment option for PAH patients that is found to offer an additional 1-3 life years gained for PAH patients compared to beraprost, currently the only treatment available in the benefit package under the National Social Health Insurance (Jaminan Kasehatan Nasional - JKN) of Indonesia. Off-label use of sildenafil for treatment of PAH is recommended to be included in the benefit package. The study results indicate that there is a need for the Ministry of Health in Indonesia to consider the use of off-label medicines in the benefit package given the strong Health Technology Assessment evidence showing the drug’s benefit to the Indonesian population.

The Toxic Effect Of Sildenafil Citrate On Adult Albino Rat Testis And The Possible Protective Role Of Royal Jelly (Histological And Immunohistochemical Study)

Background: Phosphodiesterase inhibitor was appearing as a magic tool in treatment of erectile dysfunction, however, it might lead to harmful effects in high dose and long term administration. The aim of the work: This study aimed to evaluate the toxic effect of sildenafil citrate on the histological structure of the testis of adult albino rats and the possible protective role of royal jelly. Materials and methods: Thirty five adult male albino rats were divided into 3 groups; the control group divided into (subgroup Ca, Cb and Cc), experimental group divided into (subgroup Ea and Eb) and treated group divided into (subgroup Ta and Tb). In the experimental group sildenafil citrate was given at a dose of 9 mg/kg in subgroup Ea and 13.5mg/kg in subgroup Eb orally daily for 30 days. In the treated group rats were treated by royal jelly at a dose of 100 mg/kg for 30 days orally after stoppage of sildenafil citrate. In the present study, the sperm count, histological and immunohistochemical studies were evaluated. Result : Daily oral administration of sildenafil citrate (9mg/kg and13.5 mg/kg ) for 30 day had reduced the sperm count and induced apparent degeneration with detached, distorted germ cell and congested blood vessels with significant decrease in Proliferating cell nuclear antigen Labeling Index (PCNA- LI). After royal jelly administration, there was an improvement in sperm count and histopathological changes induced by sildenafil citrate with a significant increase in PCNA -LI. Conclusion: Long-term daily use of Sildenafil citrate produced histological changes in the testis and reduced the spermatogenesis with a significant decrease in sperm count and these side effects can be prevented by using royal jelly.

Sildenafil enhances central hemodynamic responses to exercise, but not V̇o2peak, in people with diabetes mellitus.

Exercise capacity is frequently reduced in people with diabetes mellitus (DM), and the contribution of pulmonary microvascular dysfunction remains undefined. We hypothesized that pulmonary microvascular disease, measured by a novel exercise echocardiography technique termed pulmonary transit of agitated contrast (PTAC), would be greater in subjects with DM and that the use of pulmonary vasodilator agent sildenafil would improve exercise performance by reducing right ventricular afterload. Forty subjects with DM and 20 matched controls performed cardiopulmonary exercise testing and semisupine exercise echocardiography 1 h after placebo or sildenafil ingestion in a double-blind randomized crossover design. The primary efficacy end point was exercise capacity (V̇o2peak) while secondary measures included pulmonary vascular resistance, cardiac output, and change in PTAC. DM subjects were aged 44 ± 13 yr, 73% male, with 16 ± 10 yr DM history. Sildenafil caused marginal improvements in echocardiographic measures of biventricular systolic function in DM subjects. Exercise-induced increases in pulmonary artery systolic pressure and pulmonary vascular resistance were attenuated with sildenafil, while heart rate (+2.4 ±1.2 beats/min, P = 0.04) and cardiac output (+322 ± 21 ml, P = 0.03) improved. However, the degree of PTAC did not change (P = 0.93) and V̇o2peak did not increase following sildenafil as compared with placebo (V̇o2peak: 31.8 ± 9.7 vs. 32.1 ± 9.5 ml·min-1·kg-1, P = 0.42). We conclude that sildenafil administration causes modest acute improvements in central hemodynamics but does not improve exercise capacity. This may be due to the mismatch in action of sildenafil on the pulmonary arteries rather than the distal pulmonary microvasculature and potential adverse effects on peripheral oxygen extraction. NEW & NOTEWORTHY This is one of the largest and most comprehensive studies of cardiopulmonary exercise performance in people with diabetes mellitus and to our knowledge the first to assess the effect of sildenafil using detailed echocardiographic measures during incremental exercise. Sildenafil attenuated the rise in pulmonary vascular resistance while augmenting cardiac output and intriguingly heart rate, without conferring any improvement in exercise capacity. The enhanced central hemodynamic indexes may have been offset by reduced peripheral O2 extraction.

388 A multicenter study on the use of Sildenafil for lymphatic malformation in children

Lymphatic malformations (LMs) are progressive, congenital vascular anomalies that arise due to developmental dysplasia of the lymphatic network in utero. There is no FDA approved treatment. It has been hypothesized that the therapeutic effects of sildenafil may result from simple smooth muscle relaxation, which facilitate lymphatic drainage leading to decompression of the malformation. To date, this double-blind, placebo controlled multicenter study has enrolled 15 patients 6 mo to 10 yr of age with LM over 3 cm in diameter. Participants were randomized at 2:1 ratio, that is two sildenafil treated subjects for each placebo treated subject. The subjects randomized to placebo will have the option to begin a 20-wk open label treatment with sildenafil. The subjects were evaluated in clinic at wks 4, 12, 20, 32. Telephone interviews were conducted at wks 2, 8 and 16. Laboratory and MRI evaluations were obtained at baseline and wk 20. Volume changes from MRI evaluation were analyzed. Physician and parent’s clinical assessments of LM were documented. There are no serious adverse events reported. Percentage of volumetric change trend to decrease in sildenafil group, in contrast to placebo group trending to increase (-0.47 v.s. 5.88). Statistical significance was not achieved due to small cohort size. Thus, our interim analysis has demonstrated safety of sildenafil treatment in young children with LM. Although not statistically significant, there appear to be some benefit in softening and reducing distortion of LM . Intra-object analysis showed more volume reduction when patients transition from placebo to sildenafil treatment.

Proconvulsant effects of sildenafil citrate on pilocarpine-induced seizures: Involvement of cholinergic, nitrergic and pro-oxidant mechanisms

Sildenafil is a phosphodiesterase 5 inhibitor used for the treatment of erectile dysfunction and pulmonary hypertension. Proconvulsant effect is a serious adverse event associated with sildenafil use. Here, we investigated the possible proconvulsant effects of sildenafil in pilocarpine (PILO)-induced seizures model, which mimics some aspects of temporal lobe epilepsy. We also evaluated sildenafil’s effects on hippocampal markers related to PILO-induced seizure, for instance, acetylcholinesterase (AChE) activity, oxidative stress and nitric oxide (NO) markers, namely nitrite, inducible NO synthase (iNOS) and neuronal NOS (nNOS). The influences of muscarinic receptors blockade on sildenafil proconvulsant effects and brain nitrite levels were also evaluated. Male mice were submitted to single or repeated (7 days) sildenafil administration (2.5, 5, 10 and 20 mg/kg). Thirty minutes later, PILO was injected and mice were further evaluated for 1 h for seizure activity. Sildenafil induced a dose- and time-progressive proconvulsant effect in PILO-induced seizures. Sildenafil also potentiated the inhibitory effect of PILO in AChE activity and induced a further increase in nitrite levels and pro-oxidative markers, mainly in the hippocampus. Repeated sildenafil treatment also increased the hippocampal expression of iNOS and nNOS isoforms, while the blockade of muscarinic receptors attenuated both sildenafil-induced proconvulsant effect and brain nitrite changes. Our data firstly demonstrated the proconvulsant effect of sildenafil in PILO-model of seizures. This effect seems to be related to an increased cholinergic-nitrergic tone and pro-oxidative brain changes. Also, our findings advert to caution in using sildenafil for patients suffering from neurological conditions that reduces seizure threshold, such as epilepsy.

Transient global amnesia associated with sildenafil use. Report of one case

A 69 years old male with erectile dysfunction lasting 2 years, took 50 mg of sildenafil for having sex with his wife at about 6 o'clock in the morning. One hour later his wife detected that he had an anterograde memory impairment: this was interpreted as a confusional state. The neurological examination suggested a transient global amnesia (TGA). EEG and cerebral magnetic resonance imaging were non-informative and memory deficits resolved within 24 h. Therefore, a TGA was diagnosed. Since no other trigger was detectable, sildenafil was deemed responsible for its occurrence.

STRIDER NZAus: a multicentre randomised controlled trial of sildenafil therapy in early-onset fetal growth restriction.

To assess the effect of maternal sildenafil therapy on fetal growth in pregnancies with early-onset fetal growth restriction. A randomised placebo-controlled trial. Thirteen maternal-fetal medicine units across New Zealand and Australia. Women with singleton pregnancies affected by fetal growth restriction at 22+0 to 29+6 weeks. Women were randomised to oral administration of 25 mg sildenafil citrate or visually matching placebo three times daily until 32+0 weeks, birth or fetal death (whichever occurred first). The primary outcome was the proportion of pregnancies with an increase in fetal growth velocity. Secondary outcomes included live birth, survival to hospital discharge free of major neonatal morbidity and pre-eclampsia. Sildenafil did not affect the proportion of pregnancies with an increase in fetal growth velocity; 32/61 (52.5%) sildenafil-treated, 39/57 (68.4%) placebo-treated [adjusted odds ratio (OR) 0.49, 95% CI 0.23-1.05] and had no effect on abdominal circumference Z-scores (P = 0.61). Sildenafil use was associated with a lower mean uterine artery pulsatility index after 48 hours of treatment (1.56 versus 1.81; P = 0.02). The live birth rate was 56/63 (88.9%) for sildenafil-treated and 47/59 (79.7%) for placebo-treated (adjusted OR 2.50, 95% CI 0.80-7.79); survival to hospital discharge free of major neonatal morbidity was 42/63 (66.7%) for sildenafil-treated and 33/59 (55.9%) for placebo-treated (adjusted OR 1.93, 95% CI 0.84-4.45); and new-onset pre-eclampsia was 9/51 (17.7%) for sildenafil-treated and 14/55 (25.5%) for placebo-treated (OR 0.67, 95% CI 0.26-1.75). Maternal sildenafil use had no effect on fetal growth velocity. Prospectively planned meta-analyses will determine whether sildenafil exerts other effects on maternal and fetal/neonatal wellbeing. Maternal sildenafil use has no beneficial effect on growth in early-onset FGR, but also no evidence of harm.

Sildenafil/Viagra in the treatment of premature ejaculation.

The arrival of Pfizer's blue pill Sildenafil in 1998 brought a great relief both to patient and physician signalling the start of a great era of medical therapy in sexual medicine. Since then the sexual medicine experts have been prescribing sildenafil in erectile dysfunction with acceptable minor adverse events. But the use of sildenafil in premature ejaculation (PE) is still debated. 2018 being the 20th anniversary of sildenafil, we have compiled interesting facts about the role of sildenafil in PE from various original articles, systematic reviews, meta-analyses, economic brochures and sexual medicine committee guidelines. The major issues in most of these studies were the heterogeneity in the definition of PE and estimating the exact ejaculatory latency time. This perspective article highlights the positive role of sildenafil in the management of PE (even without ED) with acceptable adverse events. Now that we have a standardised definition of PE from International Society of Sexual Medicine (ISSM) and a psychogenic component in PE definition, more randomised placebo-controlled studies are required to further establish its role.

Effect of sildenafil on stable chronic heart failure: a prospective randomized-controlled clinical trial

Background Patients with systolic heart failure (HF) who develop secondary pulmonary hypertension have reduced exercise capacity and increased mortality compared with HF patients without pulmonary hypertension. A defective nitric oxide signaling is involved in left ventricular (LV) diastolic abnormalities and remodeling. Phosphodiesterase type 5 inhibition, by blocking degradation of nitric oxide second-messenger cyclic guanosine monophosphate, might be beneficial. Aim of the study In our study, we tested the effects of phosphodiesterase type 5 inhibition (sildenafil) on LV ejection fraction, diastolic function, pulmonary artery pressure, and clinical status. Patients, methods, and results One hundred HF patients (New York Heart Association classes II–IV) were assigned randomly to placebo or sildenafil (50 mg three times per day) for 6 months, with assessment at the first and 6 months of LV ejection fraction, diastolic function, pulmonary artery systolic pressure, and exercise performance (using 6 min walk test). The two groups studied were similar in terms of age, sex distribution, etiology of cardiomyopathy, the prevalence of chronic atrial fibrillation, LVEDD, LA dimensions, and pulmonary artery pressure as well as drug therapy is given to each group all through the study period (P > 0.05). After 1 month of therapy, there was a significant increase in LV ejection fraction and a decrease in pulmonary artery systolic pressure in the sildenafil group (P 0.05). Doppler-derived variables of LV diastolic function improved significantly in the sildenafil group (P 0.05). Over 6 months of therapy and follow-up, LV ejection fraction increased from 31.5 ± 5.4 to 36.4 ± 3.5 and the difference was not significant between the two groups (P > 0.05), whereas in the sildenafil group, ejection fraction % increased significantly from 30.6 ± 4.5% at baseline to 45.6 ± 5.4% (P 0.05), whereas in the sildenafil group, it decreased significantly from 48.3 ± 17.7 to 28.4 ± 6.4 mmHg (P Conclusion In patients with HF, long-term use of sildenafil was well tolerated. This therapeutic regimen (50 mg three times per day) promoted a sustained significant improvement in LV systolic and diastolic function properties in comparison with placebo.

Relationship between endometrial thickness and pregnancy outcomes based on frozen-thawed embryo transfer cycles

Objective: To explore the relationship between endometrial thickness and clinical pregnancy outcomes in frozen-thawed embryo transfer cycles. Methods: A prospective study was performed for 1 475 frozen-thawed embryo transfer cycles at Peking University People's Hospital from January 2014 to December 2015. The patients were divided into different groups according to endometrial thickness of ovulation day in natural menstrual cycles or endometrial transformation day in hormone replacement cycles;patients with thin endometrium were enndometrial thickness ≤6 mm. Then the clinical pregnancy outcomes including clinical pregnancy rate, embryo implantation rate, abortion rate, multiple birth rate and live birth rate were analyzed. Results: In all, 1 475 frozen-thawed embryo transfer cycles were analyzed. The mean age of patients was (32.5±3.9) years old and mean endometrial thickness was (9.2±1.9) mm, and mean number of embryos was 2.03±0.37. The study included 518 (35.1%) natural menstrual cycles and 957 (64.9%) hormone replacement cycles. The number of embryo-transfer cycles and blastocyst-transfer cycles were respectively 700 (47.5%) and 775 (52.5%) . The overall clinical pregnancy rate, embryo implantation rate, abortion rate, multiple birth rate and live birth rate were 54.4%, 35.7%, 23.3%, 24.1%, 43.9%, respectively. The ectopic pregnancy rate in the study was 0.6%. In patients with thin endometrium,there were significant differences in 2 pronucleus count (P=0.016) and available embryo count (P=0.024) between cycles that resulted in pregnancy and those that did not;besides, the use of sildenafil and growth hormone did not improve pregnancy outcomes in patients with thin endometrium (P=0.183, P=0.400) . The clinical pregnancy rate, embryo implantation rate and live birth rate of embryo-transfer and blastocyst-transfer were similar in patients with thin endometrium (all P>0.05) . Conclusions: Patients with thin endometrium have poor pregnancy outcomes. The clinical pregnancy rate, embryo implantation rate and live birth rate of embryo-transfer and blastocyst-transfer are similar in patients with thin endometrium. Compared thin endometrium and non-thin endometrium patients, the clinical pregnancy rate and live birth rate of blastocysts have more substantial decline than those of embryos. Improving the quality of embryo could improve the pregnancy outcome of patients with thin endometrium. Sildenafil and growth hormone could not improve pregnancy outcome in patients with thin endometrium.

Cost Effectiveness of Bosentan for Pulmonary Arterial Hypertension: A Systematic Review.

Objectives Although many studies have reported on the cost-effectiveness of bosentan for treating pulmonary arterial hypertension (PAH), a systematic review of economic evaluations of bosentan is currently lacking. Objective evaluation of current pharmacoeconomic evidence can assist decision makers in determining the appropriate place in therapy of a new medication. Methods Systematic literature searches were conducted in English-language databases (MEDLINE, EMBASE, EconLit databases, and the Cochrane Library) and Chinese-language databases (China National Knowledge Infrastructure, WanFang Data, and Chongqing VIP) to identify studies assessing the cost-effectiveness of bosentan for PAH treatments. Results A total of 8 published studies were selected for inclusion. Among them were two studies comparing bosentan with epoprostenol and treprostinil. Both results indicated that bosentan was more cost-effective than epoprostenol, while the results of bosentan and treprostinil were not consistent. Four studies compared bosentan with other endothelin receptor antagonists, which indicated ambrisentan might be the drug of choice for its economic advantages and improved safety profile. Only two economic evaluations provided data to compare bosentan versus sildenafil, and the results favored the use of sildenafil in PAH patients. Four studies compared bosentan with conventional, supportive, or palliative therapy, and whether bosentan was cost-effective was uncertain. Conclusions Bosentan may represent a more cost-effective option compared with epoprostenol and conventional or palliative therapy. There was unanimous agreement that bosentan was not a cost-effective front-line therapy compared with sildenafil and other endothelin receptor antagonists. However, high-quality cost-effectiveness analyses that utilize long-term follow-up data and have no conflicts of interest are still needed.

The Clinical Effects of Sildenafil for Erection in Patients after Kidney Transplantation: A Meta-Analysis

Background: With the wide use of sildenafil in kidney-transplanted patients, it is vital to recognize the effectiveness and safety in clinical practice. Methods: Full-text articles involving the application of sildenafil after renal transplantation searched out in multiple databases were reviewed. All the meta-analyses were performed with Review Manager 5.0 software and bias analysis of the studies were conducted to examine the quality of articles. In addition, to estimate possible publication bias, funnel plot and the Egger’s test were used. Result: Finally 7 articles eventually satisfied the inclusion criteria. The penetration ability and maintenance frequency in sildenafil group were much larger than those of control group. Except orgasmic function, domains of the International Index of Erectile Function have showed larger scores in sildenafil group than those of control group. No significant difference of the concentration of cyclosporine was observed between sildenafil and control group. Conclusion: In conclusion, this study showed that treatment with sildenafil in renal allograft recipients with erectile dysfunction is a valid and safe option.

Sildenafil for the treatment of preeclampsia, an update: should we still be enthusiastic?

Preeclampsia is a hypertensive disorder of pregnancy and the clinical manifestation of severe endothelial dysfunction associated with maternal and foetal morbidity and mortality. The primum movens of the disease is the defect of invasion of the uterine arteries by foetal syncytiotrophoblasts, which causes a maladaptive placental response to chronic hypoxia and the secretion of the soluble form of type 1 vascular growth endothelial factor receptor, also called soluble fms-like tyrosine kinase 1 (sFlt-1), the major player in the pathophysiology of the disease. Among its different effects, sFlt-1 induces abnormal sensitivity of the maternal vessels to the vasoconstrictor angiotensin II. This leads to the hypertensive phenotype, recently shown to be abrogated by the administration of sildenafil citrate, which can potentiate the vasodilatory mediator nitrite oxide. This review focuses on the mechanisms of maternal endothelial dysfunction in preeclampsia and discusses the therapeutic window of sildenafil use in the context of preeclampsia, based on the results from preclinical studies and clinical trials. Safety issues recently reported in neonates have considerably narrowed this window.

Sildenafil Use in Children with Pulmonary Hypertension

To assess the demographics, treatment algorithm, and outcomes in a large cohort of children treated with sildenafil. A retrospective cohort study of children with pulmonary hypertension (PH) treated with sildenafil at a single institution between 2004 and 2015. Baseline and follow-up data collected by chart review. There were 269 children included in this study: 47 with idiopathic pulmonary arterial hypertension, 53 with congenital heart disease, 135 with bronchopulmonary dysplasia, 24 with congenital diaphragmatic hernia, and 7 with other causes. Sildenafil was initial monotherapy in 84.8% and add-on therapy in 15.2%. Median follow-up time was 3.1 years (2 weeks-12.4 years). On follow-up, 99 (37%) remained on sildenafil or transitioned to tadalafil, 93 (35%) stopped sildenafil for improvement in PH, 54 (20%) died, and 20 (7%) were lost to follow-up. PH was most likely to improve in those with bronchopulmonary dysplasia, allowing for the discontinuation of sildenafil in 45%. Eighteen deaths were related to PH and 36 from other systemic causes. Two patients stopped sildenafil owing to airway spasm with desaturation. Overall survival was significantly lower in World Health Organization group 3 PH (bronchopulmonary dysplasia and congenital diaphragmatic hernia) vs group 1 (idiopathic pulmonary arterial hypertension and congenital heart disease), P = .02. In this retrospective experience in children with mainly World Health Organization groups 1 and 3 PH, low-dose sildenafil was well-tolerated, safe, and had an acceptable side effect profile. Although patients with group 3 PH have high mortality, survivors have a high likelihood of PH improving.

Sedentary behavior is associated with physical activity, functional capacity, and a history of stroke in patients with heart failure. A cross-sectional study

Aims: Sedentary behavior (SB) has emerged as an important risk factor for poor health. Evidence showed that patients with heart failure (HF) exhibit high levels of SB, and that high SB increases mortality among such patients. We aimed to identify factors associated with SB in HF patients. Methods: A cross-sectional study was carried out with adults with HF and categorized under New York Heart Association (NYHA) functional class I-III. Sociodemographic, clinical, and health information were gathered. Evaluation of SB (by sitting time) and moderate-to-vigorous physical activity (MVPA) was performed by self-reported measures. Functional capacity was assessed using the Duke Activity Status Index. Simple and multivariate linear regression analyses were performed to identify the most suitable predictive model. Results: The sample (n = 80) comprised predominantly of patients in functional class I, men, and with an average age of 50.8 years. Time spent on SB totaled to 7.69 ± 2.35 h/day. Weekly volume of MVPA, functional capacity, and previous stroke were predictors of higher SB. Using simple linear regression analysis, the variables body mass index, quality of life, NYHA functional class, total comorbidities, dyslipidemia, MVPA in the leisure domain, and the use of diuretics, statins, and sildenafil were shown to have a statistically significant association with SB. Conclusion: In patients with HF, a longer time spent in SB was associated with low volumes of MVPA, low functional capacity, and history of stroke. More studies are needed to corroborate these findings.