Impact of Oral Sildenafil on Exercise Performance in Children and Young Adults After the Fontan Operation: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial (original) (raw)
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Circulation, 2007
Background-Patients with systolic heart failure (HF) who develop secondary pulmonary hypertension (PH) have reduced exercise capacity and increased mortality compared with HF patients without PH. We tested the hypothesis that sildenafil, an effective therapy for pulmonary arterial hypertension, would lower pulmonary vascular resistance and improve exercise capacity in patients with HF complicated by PH. Methods and Results-Thirty-four patients with symptomatic HF and PH were randomized to 12 weeks of treatment with sildenafil (25 to 75 mg orally 3 times daily) or placebo. Patients underwent cardiopulmonary exercise testing before and after treatment. The change in peak V O 2 from baseline, the primary end point, was greater in the sildenafil group (1.8Ϯ0.7 mL · kg Ϫ1 · min Ϫ1 ) than in the placebo group (Ϫ0.27 mL · kg Ϫ1 · min Ϫ1 ; Pϭ0.02). Sildenafil reduced pulmonary vascular resistance and increased cardiac output with exercise (PϽ0.05 versus placebo for both) without altering pulmonary capillary wedge or mean arterial pressure, heart rate, or systemic vascular resistance. The ability of sildenafil treatment to augment peak V O 2 correlated directly with baseline resting pulmonary vascular resistance (rϭ0.74, Pϭ0.002) and indirectly with baseline resting right ventricular ejection fraction (rϭϪ0.64, Pϭ0.01). Sildenafil treatment also was associated with improvement in 6-minute walk distance (29 m versus placebo; Pϭ0.047) and Minnesota Living With Heart Failure score (Ϫ14 versus placebo; Pϭ0.01). Subjects in the sildenafil group experienced fewer hospitalizations for HF and a higher incidence of headache than those in the placebo group without incurring excess serious adverse events.
Sildenafil Improves Exercise Hemodynamics and Oxygen Uptake in Patients With Systolic Heart Failure
Circulation, 2006
Background— Heart failure (HF) is frequently associated with dysregulation of nitric oxide–mediated pulmonary vascular tone. Sildenafil, a type 5 phosphodiesterase inhibitor, lowers pulmonary vascular resistance in pulmonary hypertension by augmenting intracellular levels of the nitric oxide second messenger, cyclic GMP. We tested the hypothesis that a single oral dose of sildenafil (50 mg) would improve exercise capacity and exercise hemodynamics in patients with chronic systolic HF through pulmonary vasodilation. Methods and Results— Thirteen patients with New York Heart Association class III HF underwent assessment of right heart hemodynamics, gas exchange, and first-pass radionuclide ventriculography at rest and with cycle ergometry before and 60 minutes after administration of 50 mg of oral sildenafil. Sildenafil reduced resting pulmonary arterial pressure, systemic vascular resistance, and pulmonary vascular resistance, and increased resting and exercise cardiac index ( P <...
Sildenafil Does Not Improve Peak Exercise Capacity During Acute Hypoxia In Trained Men Or Women
Medicine & Science in Sports & Exercise, 2010
Sildenafil improves oxygen delivery and maximal exercise capacity at very high altitudes (C4,350 m), but it is unknown whether sildenafil improves these variables and longer-duration exercise performance at moderate and high altitudes where competitions are more common. The purpose of this study was to determine the effects of sildenafil on cardiovascular hemodynamics, arterial oxygen saturation (SaO 2 ), peak exercise capacity (W peak ), and 15-km time trial performance in endurance-trained subjects at simulated moderate (MA; *2,100 m, 16.2% F I O 2 ) and high (HA; *3,900 m, 12.8% F I O 2 ) altitudes. Eleven men and ten women completed two HA W peak trials after ingesting placebo or 50 mg sildenafil. Subjects then completed four exercise trials (30 min at 55% of altitudespecific W peak ? 15-km time trial) at MA and HA after ingesting placebo or 50 mg sildenafil. All trials were performed in randomized, counterbalanced, and double-blind fashion. Sildenafil had little influence on cardiovascular hemodynamics at MA or HA, but did result in higher SaO 2 values (?3%, p \ 0.05) compared to placebo during steady state and time trial exercise at HA. W peak at HA was 19% lower than SL (p \ 0.001) and was not significantly affected by sildenafil. Similarly, the significantly slower time trial performance at MA (28.1 ± 0.5 min, p = 0.016) and HA (30.3 ± 0.6 min, p \ 0.001) compared to SL (27.5 ± 0.6 min) was unaffected by sildenafil. We conclude that sildenafil is unlikely to exert beneficial effects at altitudes \4,000 m for a majority of the population. * Significantly different from SL; p \ 0.05 Eur J Appl Physiol (2011) 111:3031-3040 3035 SaO 2 , % 94 ± 0.6 89 ± 0.4* 89 ± 0.4* 77 ± 0.9* à 79 ± 1.0* à Values are mean ± SE, n = 11 men and 10 women SL sea level, HA simulated high altitude, MA simulated moderate altitude, HR heart rate * Significantly different from SL Significantly different from placebo at same simulated altitude à Significantly different from same condition at MA; p \ 0.05 Eur J Appl Physiol (2011) 111:3031-3040 3037
Pediatric Cardiology, 2012
The objective of this study was describe the impact of sildenafil on echocardiographic measures of myocardial performance in children and young adults with a functional single-ventricle physiology late after Fontan surgery. A double-blind, placebo-controlled, crossover trial was conducted in children and young adults after the Fontan operation at a single pediatric center. Subjects were randomized to receive placebo or sildenafil (20 mg tid) for 6 weeks. After a 6-week washout period, subjects were crossed for an additional 6 weeks. Each subject underwent an echocardiogram at the start and finish of each phase. A total of 27 subjects completed study testing at a mean age of 14.9 years and a mean time from Fontan surgery of 11.3 years. After sildenafil, subjects demonstrated improvement in their myocardial performance index (MPI;-0.051; 95% CI-0.095,-0.0077; p 0.02) and in the product of the velocity time integral (VTI) of the dominant outflow tract and the heart rate (HR; 110 cm 9 bpm; 95% CI 7.5, 220; p = 0.04). Measures of diastolic performance, including inflow velocities, myocardial velocities, and the ratio of blood pool velocity to myocardial velocity during passive inflow, did not change. In this cohort, there were significant improvements in both the MPI and the product of the VTI 9 HR after 6 weeks of treatment with sildenafil. These findings suggest that sildenafil may be a useful therapy to improve or maintain ventricular performance in select patients after the Fontan operation.
European heart journal, 2015
Heart failure with preserved ejection fraction (HFpEF), with associated pulmonary hypertension is an increasingly large medical problem. Phosphodiesterase (PDE)-5 inhibition may be of value in this population, but data are scarce and inconclusive. In this single centre, randomized double-blind, placebo-controlled trial, we included 52 patients with pulmonary hypertension [mean pulmonary artery pressure (PAP) >25 mmHg; pulmonary artery wedge pressure (PAWP) >15 mmHg] due to HFpEF [left ventricular ejection fraction (LVEF) ≥45%]. Patients were randomized to the PDE-5 inhibitor sildenafil, titrated to 60 mg three times a day, or placebo for 12 weeks. The primary endpoint was change in mean PAP after 12 weeks. Secondary endpoints were change in mean PAWP, cardiac output, and peak oxygen consumption (peak VO2). Mean age was 74 ± 10 years, 71% was female, LVEF was 58%, median NT-proBNP level was 1087 (535-1945) ng/L. After 12 weeks, change in mean PAP was -2.4 (95% CI -4.5 to -0.3) ...
European Journal of Applied Physiology, 2011
Sildenafil improves oxygen delivery and maximal exercise capacity at very high altitudes (C4,350 m), but it is unknown whether sildenafil improves these variables and longer-duration exercise performance at moderate and high altitudes where competitions are more common. The purpose of this study was to determine the effects of sildenafil on cardiovascular hemodynamics, arterial oxygen saturation (SaO 2), peak exercise capacity (W peak), and 15-km time trial performance in endurance-trained subjects at simulated moderate (MA; *2,100 m, 16.2% F I O 2) and high (HA; *3,900 m, 12.8% F I O 2) altitudes. Eleven men and ten women completed two HA W peak trials after ingesting placebo or 50 mg sildenafil. Subjects then completed four exercise trials (30 min at 55% of altitudespecific W peak ? 15-km time trial) at MA and HA after ingesting placebo or 50 mg sildenafil. All trials were performed in randomized, counterbalanced, and double-blind fashion. Sildenafil had little influence on cardiovascular hemodynamics at MA or HA, but did result in higher SaO 2 values (?3%, p \ 0.05) compared to placebo during steady state and time trial exercise at HA. W peak at HA was 19% lower than SL (p \ 0.001) and was not significantly affected by sildenafil. Similarly, the significantly slower time trial performance at MA (28.1 ± 0.5 min, p = 0.016) and HA (30.3 ± 0.6 min, p \ 0.001) compared to SL (27.5 ± 0.6 min) was unaffected by sildenafil. We conclude that sildenafil is unlikely to exert beneficial effects at altitudes \4,000 m for a majority of the population. Keywords Arterial oxygen saturation Á Hypoxia Á Gender Á Viagra Á Exertion Communicated by Keith Phillip George. This study involved the administration of a prescription drug. Accordingly, it was under the supervision of properly licensed medical professionals. In no way do the authors advocate any usage of this drug in any form or circumstance other than under such supervision.