Sildenafil improves exercise hemodynamics in Fontan patients.
BACKGROUND
Patients with Fontan circulation have reduced exercise capacity. The absence of a presystemic pump may limit flow through the pulmonary circulation, restricting ventricular filling and cardiac output. We evaluated exercise hemodynamics and the effect of sildenafil on exercise hemodynamics in Fontan patients.


RESULTS
Ten Fontan patients (6 men, 20±4 years) underwent cardiac magnetic resonance imaging at rest and during supine bicycle exercise before and after sildenafil. Systemic ventricular volumes were obtained at rest and during low- (34±15 W), moderate- (69±29 W), and high-intensity (97±36 W) exercise using an ungated, free-breathing cardiac magnetic resonance sequence and analyzed correcting for cardiac phase and respiratory translation. Radial and pulmonary artery pressures and cGMP were measured. Before sildenafil, cardiac index increased throughout exercise (4.0±0.9, 5.9±1.1, 7.0±1.6, 7.4±1.7 L/(min·m(2)); P<0.0001) with 106±49% increase in heart rate. Stroke volume index (P=0.015) and end-diastolic volume index (P=0.001) decreased during exercise. End-systolic volume index remained unchanged (P=0.8). Total pulmonary resistance index (P=0.005) increased, whereas systemic vascular resistance index decreased during exercise (P<0.0001). Sildenafil increased cardiac index (P<0.0001) and stroke volume index (P=0.003), especially at high-intensity exercise (interaction P=0.004 and P=0.003, respectively). Systemic vascular resistance index was reduced (P<0.0001-interaction P=0.1), whereas total pulmonary resistance index was reduced at rest and reduced further during exercise (P=0.008-interaction P=0.029). cGMP remained unchanged before sildenafil (P=0.9), whereas it increased significantly after sildenafil (P=0.019).


CONCLUSIONS
In Fontan patients, sildenafil improved cardiac index during exercise with a decrease in total pulmonary resistance index and an increase in stroke volume index. This implies that pulmonary vasculature represents a physiological limitation, which can be attenuated by sildenafil, the clinical significance of which warrants further study.
Departments of Adult Congenital Cardiology.
Alexander
A
Van De Bruaene
Andre
A
La Gerche
Guido
G
Claessen
Pieter
P
De Meester
Sarah
S
Devroe
Hilde
H
Gillijns
Jan
J
Bogaert
Piet
P
Claus
Hein
H
Heidbuchel
Marc
M
Gewillig
Werner
W
Budts
D006328:Cardiac Catheterization; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005260:Female; D018729:Fontan Procedure; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery*; D006352:Heart Ventricles / Q000002:abnormalities* / Q000503:physiopathology / Q000601:surgery; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage*; D011687:Purines / Q000008:administration & dosage; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*; D055815:Young Adult
D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate
Fontan procedure; cyclic GMP; exercise; pulmonary circulation; sildenafil