sildenafil-citrate and Heart-Valve-Diseases

Background The determinants and consequences of pulmonary hypertension after successfully corrected valvular heart disease remain poorly understood. We aim to clarify the hemodynamic bases and risk factors for mortality in patients with this condition. Methods and Results We analyzed long-term follow-up data of 222 patients with pulmonary hypertension and valvular heart disease successfully corrected at least 1 year before enrollment who had undergone comprehensive hemodynamic and imaging characterization as per the SIOVAC (Sildenafil for Improving Outcomes After Valvular Correction) clinical trial. Median (interquartile range) mean pulmonary pressure was 37 mm Hg (32-44 mm Hg) and pulmonary artery wedge pressure was 23 mm Hg (18-26 mm Hg). Most patients were classified either as having combined precapillary and postcapillary or isolated postcapillary pulmonary hypertension. After a median follow-up of 4.5 years, 91 deaths accounted for 4.21 higher-than-expected mortality in the age-matched population. Risk factors for mortality were male sex, older age, diabetes mellitus, World Health Organization functional class III and higher pulmonary vascular resistance-either measured by catheterization or approximated from ultrasound data. Higher pulmonary vascular resistance was related to diabetes mellitus and smaller residual aortic and mitral valve areas. In turn, the latter correlated with prosthetic nominal size. Six-month changes in the composite clinical score and in the 6-minute walk test distance were related to survival. Conclusions Persistent valvular heart disease-pulmonary hypertension is an ominous disease that is almost universally associated with elevated pulmonary artery wedge pressure. Pulmonary vascular resistance is a major determinant of mortality in this condition and is related to diabetes mellitus and the residual effective area of the corrected valve. These findings have important implications for individualizing valve correction procedures. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00862043.

Topics: Diabetes Mellitus; Double-Blind Method; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Heart Valves; Humans; Hypertension, Pulmonary; Long Term Adverse Effects; Male; Middle Aged; Organ Size; Phosphodiesterase 5 Inhibitors; Postoperative Complications; Pulmonary Wedge Pressure; Risk Factors; Sildenafil Citrate; Vascular Resistance

We aimed to determine whether treatment with sildenafil improves outcomes of patients with persistent pulmonary hypertension (PH) after correction of valvular heart disease (VHD).. The sildenafil for improving outcomes after valvular correction (SIOVAC) study was a multricentric, randomized, parallel, and placebo-controlled trial that enrolled stable adults with mean pulmonary artery pressure ≥ 30 mmHg who had undergone a successful valve replacement or repair procedure at least 1 year before inclusion. We assigned 200 patients to receive sildenafil (40 mg three times daily, n = 104) or placebo (n = 96) for 6 months. The primary endpoint was the composite clinical score combining death, hospital admission for heart failure (HF), change in functional class, and patient global self-assessment. Only 27 patients receiving sildenafil improved their composite clinical score, as compared with 44 patients receiving placebo; in contrast 33 patients in the sildenafil group worsened their composite score, as compared with 14 in the placebo group [odds ratio 0.39; 95% confidence interval (CI) 0.22-0.67; P < 0.001]. The Kaplan-Meier estimates for survival without admission due to HF were 0.76 and 0.86 in the sildenafil and placebo groups, respectively (hazard ratio 2.0, 95% CI = 1.0-4.0; log-rank P = 0.044). Changes in 6-min walk test distance, natriuretic peptides, and Doppler-derived systolic pulmonary pressure were similar in both groups.. Treatment with sildenafil in patients with persistent PH after successfully corrected VHD is associated to worse clinical outcomes than placebo. Off-label usage of sildenafil for treating this source of left heart disease PH should be avoided. The trial is registered with ClinicalTrials.gov, number NCT00862043.

Topics: Aged; Double-Blind Method; Female; Heart Failure; Heart Valve Diseases; Humans; Hypertension, Pulmonary; Male; Placebos; Pulmonary Wedge Pressure; Sildenafil Citrate; Treatment Outcome; Vasodilator Agents

Sildenafil (Viagra, Pfizer) is being used to treat pulmonary hypertension (PH). However, there are limited data on the effects of sildenafil on patients with PH after left-sided valvular surgery. The purpose of this study was to determine the optimal dosage and the effects of sildenafil on prognosis of patients with PH after left-sided valvular surgery.. This randomised controlled trial, double-blind study enrolled patients with PH undergoing left-sided valvular surgery in our hospital from January to December, 2010. Ninety patients were enrolled. And 0.5 mg/kg sildenafil citrate or placebo was administered through nasogastric tubes, the haemodynamics changes in the 0.5/1/2/4 hours were assessed. The sildenafil citrate/placebo was continued to the discharges and the early prognoses of these patients were compared.. Compared with placebo, a 0.5 mg/kg dose of sildenafil significantly reduced the time of mechanical ventilation, stay-in-ICU and hospitalisation duration.. Sildenafil might be beneficial to the early prognosis of patients with PH after left-sided valvular surgery.

Topics: Aged; Cardiac Surgical Procedures; Female; Heart Valve Diseases; Humans; Hypertension, Pulmonary; Length of Stay; Male; Middle Aged; Piperazines; Postoperative Period; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

The goal of this study was to examine the effects of coadministration of sildenafil and inhaled nitric oxide (iNO) in patients with out-of-proportion pulmonary hypertension who underwent cardiac valve replacement surgery.. Twenty consecutive cardiac surgery patients with out-of-proportion pulmonary hypertension were randomly assigned postoperatively into 2 groups: group A received 10 ppm of iNO followed by sildenafil (100 mg) orally 30 minutes later, and group B initially received sildenafil (100 mg) orally followed by 10 ppm of iNO 60 minutes later. Hemodynamic and gas exchange data were obtained at baseline, after administration of either iNO or sildenafil alone, and at 90 minutes from baseline. In group A, iNO resulted in a significant reduction in mean pulmonary artery pressure (MPAP) and pulmonary vascular resistance index (PVRI) (by 9.6% and 20.8%, respectively). In group B, sildenafil administration also resulted in a significant decrease in mean arterial pressure, MPAP, pulmonary artery occlusive pressure, PVRI, and systemic vascular resistance index but also in the PaO(2)/inspired fraction of oxygen ratio (by 18.7%, 22.0%, 15.7%, 31.6%, 21.3%, and 14%, respectively). In both groups, the coadministration of the 2 drugs resulted in a significant further reduction of mean arterial pressure, MPAP, pulmonary artery occlusive pressure, systemic vascular resistance index, and PVRI, whereas cardiac index and mixed venous oxygen saturation remained unchanged. The hypoxemia after sildenafil administration in group B improved after the coadministration of iNO, and thus PaO(2)/inspired fraction of oxygen returned to values near baseline.. In this study, the postoperative coadministration of iNO and oral sildenafil in patients with out-of-proportion pulmonary hypertension undergoing cardiac surgery is safe and results in an additive favorable effect on pulmonary arterial pressure and pulmonary vascular resistance, without systemic hypotension and ventilation/perfusion mismatch.

Topics: Administration, Inhalation; Administration, Oral; Aged; Blood Pressure; Cardiac Surgical Procedures; Drug Therapy, Combination; Female; Heart Valve Diseases; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Nitric Oxide; Piperazines; Postoperative Period; Prospective Studies; Pulmonary Gas Exchange; Purines; Retrospective Studies; Sildenafil Citrate; Sulfones; Vascular Resistance; Vasodilator Agents

Sildenafil and beraprost, as orally available pulmonary vasodilators, are used increasingly to treat pulmonary hypertension (PH). An evaluation was made, in patients with PH undergoing valvular heart surgery, as to whether preoperative combined oral sildenafil and beraprost treatment could induce synergistic and prolonged pulmonary vasodilation, or result in a loss of pulmonary selectivity.. Fifty patients scheduled for valvular heart surgery with a mean pulmonary arterial pressure (PAP) > 30 mmHg were randomly assigned to receive either 50 mg oral sildenafil + 40 microg beraprost, or a placebo, 15 min before the induction of anesthesia. Hemodynamic variables were measured intraoperatively.. The treatment group had a significantly lower systemic vascular resistance index at 60 min after medication. No other significant intergroup differences in hemodynamic variables were observed. In addition, significantly more patients in the treatment group required vasopressor therapy. In both groups, the PAP was significantly reduced by general anesthesia, and almost normalized after valvular heart surgery.. Preoperative oral sildenafil and beraprost treatment resulted in a loss of pulmonary selectivity, and did not provide any additional pulmonary vasodilation or favorable perioperative hemodynamics in patients with PH undergoing valvular heart surgery.

Topics: Adult; Aged; Anesthesia, General; Blood Pressure; Comorbidity; Drug Therapy, Combination; Epoprostenol; Female; Heart Valve Diseases; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Piperazines; Preoperative Care; Purines; Sildenafil Citrate; Sulfones; Vascular Resistance; Vasoconstrictor Agents; Vasodilator Agents

Pulmonary hypertension remains a major problem during the perioperative period for surgical correction of long-standing valvular heart disease. Sildenafil citrate (INN sildenafil) is a selective phosphodiesterase type 5 inhibitor that is being increasingly recognized as a treatment modality for pulmonary hypertension. There is lack of evidence, however, regarding its pulmonary vasodilatory effect in anesthetized cardiac surgical patients. We therefore evaluated the effects of sildenafil on hemodynamics in patients with concomitant pulmonary hypertension undergoing valvular heart surgery in a controlled, prospective, randomized, double-blind trial.. Fifty-three patients scheduled for valvular heart surgery with mean pulmonary arterial pressure greater than 30 mm Hg were randomly treated with either 50 mg oral sildenafil (n = 26) or placebo (n = 27) 10 minutes before induction of anesthesia. Hemodynamic variables were measured 5 minutes after induction of anesthesia (baseline) and at 30 and 60 minutes after medication.. Patient characteristics and baseline hemodynamics were similar between groups. Systolic and mean pulmonary arterial pressures and pulmonary vascular resistance were significantly lower in the sildenafil group at 30 minutes after medication, without any changes in mean systemic arterial pressure and systemic vascular resistance.. Sildenafil produced significant pulmonary vasodilatory effect relative to placebo in anesthetized cardiac surgical patients with pulmonary hypertension. With respect to the predominant selectivity of sildenafil to pulmonary vasculature shown in this study and other potentially beneficial effects such as myocardial protection, use of sildenafil in the intraoperative period in cardiac surgical patients with pulmonary hypertension should be considered.

Topics: Administration, Oral; Double-Blind Method; Female; Heart Valve Diseases; Humans; Hypertension, Pulmonary; Intraoperative Period; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Purines; Sildenafil Citrate; Sulfones

The adult worms of Angiostrongylus vasorum reside in the pulmonary artery of dogs and can lead to cardiac, respiratory, and central neurologic signs. Due to luminal obstruction and perivascular inflammation of the pulmonary artery branches, pulmonary hypertension can arise. Pulmonary hypertension, in turn, can lead to severe damage of the right-sided cardiac structures, leading to right ventricular remodeling and tricuspid valve regurgitation.. An 8-year-old neutered female English Cocker Spaniel was presented to the author's institution because of abdominal distention and exercise intolerance. Ascites caused by congestive right-sided heart failure was found to be responsible for these problems. The underlying etiology of the right-sided heart failure was a severe pulmonary hypertension caused by Angiostrongylus vasorum infection. Echocardiography revealed, in addition to a severe concentric and eccentric right ventricular hypertrophy, right atrial and pulmonary trunk dilation, severe tricuspid valve regurgitation, and a systolic flail of the anterior leaflet of the tricuspid valve, resulting from ruptured chordae tendineae. As a coincidental finding, a congenital mitral stenosis was found. Oral therapy was initiated with daily administration of fenbendazole for 2 weeks along with daily administration of oral sildenafil until the re-check examination. At the 6-week re-check the dog showed full clinical and partial echocardiographic recovery, and both the blood antigen test for Angiostrongylus vasorum and the fecal Baermann larva isolation test were negative. When the sildenafil therapy was ceased after tapering the daily dosage, the owner reported recurrence of abdominal distension. Re-starting the sildenafil therapy resulted in resolution of this problem. The dog was reported to be clinically healthy with daily sildenafil administration 7 months after the initial presentation.. The present case report describes a dog where angiostrongylosis led to congestive right-sided heart failure resulting from severe pulmonary hypertension. The secondary right ventricular eccentric hypertrophy together with suspected papillary muscular ischemia were the suspected cause of the ruptured major tricuspid chordae tendineae, which led to a severe tricuspid valve regurgitation. Despite eradication of the worms, the severe pulmonary hypertension persisted. Treatment with daily oral sildenafil, a pulmonary arterial vasodilator, was enough to keep the dog free of clinically apparent ascites.

Topics: Angiostrongylus; Animals; Antinematodal Agents; Dog Diseases; Dogs; Female; Fenbendazole; Heart Failure; Heart Valve Diseases; Hypertension, Pulmonary; Sildenafil Citrate; Strongylida Infections; Tricuspid Valve; Vasodilator Agents

The phosphodiesterase-5 inhibitor sildenafil was developed for the treatment of pulmonary hypertension. The authors investigated the efficacy and safety of sildenafil in the early postoperative period after mitral valve surgery in patients with pulmonary hypertension.. A double-blind, placebo-controlled randomized trial was performed.. The trial was performed in a single tertiary referral center.. Fifty consecutive patients who experienced pulmonary hypertension and underwent mitral valve surgery.. Patients were randomly assigned to the following 2 groups: 25 patients received 20 mg sildenafil every 8 hours, and the remaining 25 patients received placebo during the same period. Hemodynamic parameters were studied by using a pulmonary artery catheter at baseline and every 6 hours up to 36 hours.. Patients who received sildenafil showed a decrease in mean pulmonary pressure, from 32 ± 7 mmHg at baseline to 26 ± 3 mmHg after 36 hours, whereas no change was seen in patients who received placebo (mean pulmonary pressure 34 ± 6 mmHg at baseline and 35 ± 5 mmHg after 36 h) (p < 0.001). No significant changes in systemic hemodynamic and oxygenation were observed. Patients who received sildenafil compared with those who received placebo had a median mechanical lung ventilation time of 16 (10-31) hours versus 19 (13-41) hours (p = 0.431), intensive care unit stay of 74 (44-106) hours versus 91 (66-141) hours (p = 0.410), and a total hospitalization stay of 7 (5-10) days versus 11 (7-15) days (p = 0.009).. The immediate postoperative administration of sildenafil after mitral valve surgery is safe. Sildenafil demonstrates a favorable decreasing effect on pulmonary vascular pressure without systemic hypotension and ventilation-perfusion mismatch.

Topics: Aged; Double-Blind Method; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Hypertension, Pulmonary; Male; Mitral Valve; Phosphodiesterase 5 Inhibitors; Postoperative Care; Prospective Studies; Pulmonary Wedge Pressure; Sildenafil Citrate; Time Factors; Treatment Outcome; Vascular Resistance

Topics: Double-Blind Method; Heart Diseases; Heart Valve Diseases; Humans; Hypertension, Pulmonary; Sildenafil Citrate

Topics: Double-Blind Method; Heart Valve Diseases; Humans; Hypertension, Pulmonary; Sildenafil Citrate

Topics: Double-Blind Method; Heart Valve Diseases; Humans; Hypertension, Pulmonary; Sildenafil Citrate

Topics: Administration, Oral; Female; Heart Valve Diseases; Humans; Hypertension, Pulmonary; Intraoperative Period; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Purines; Sildenafil Citrate; Sulfones

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Blood Proteins; Drug Administration Schedule; Drug Synergism; Erectile Dysfunction; Gingival Hemorrhage; Half-Life; Heart Valve Diseases; Humans; International Normalized Ratio; Male; Piperazines; Postoperative Complications; Protein Binding; Purines; Ranitidine; Sildenafil Citrate; Sulfones; Thrombosis; Warfarin