Effects of sildenafil citrate (viagra) on cardiac repolarization and on autonomic control in subjects with chronic heart failure.
BACKGROUND
Cases of sudden death associated with sildenafil citrate use have been reported in men with coronary artery disease. The aim of this study was to investigate the drug's effect on cardiac repolarization and sinus autonomic and vascular control in men with mild chronic heart failure (CHF; New York Heart Association classification II). Changes in these variables could predispose patients to malignant ventricular arrhythmias.


METHODS
We measured QT dispersion, the QT-RR slope, and the index of QT variability (QTVI) and analyzed spectral power of RR and systolic blood pressure variability in 10 men with dilated cardiomyopathy and in 10 control subjects after administration of a single 50-mg oral dose of sildenafil citrate or placebo at rest (not followed with any attempt at intercourse).


RESULTS
In both groups, oral sildenafil citrate decreased the systolic blood pressure (P <.05) and increased the heart rate (P <.05). In subjects with CHF, it also increased the QT-RR (P <.001) and QTVI (from -0.45 +/- 0.07 to -0.27 +/- 0.07; P <.001), but in controls, it increased the QTVI (from -1.20 +/- 0.08 to -0.78 +/-.014; P <.001). In these subjects and controls, oral sildenafil citrate induced a significant reduction in high frequency, expressed in absolute power (subjects with CHF: from 4.04 +/- 0.14 to 3.43 +/- 0.16 natural logarithm ms2; P <.001; controls: from 5.61 +/- 0.44 to 4.98 +/- 0.32 natural logarithm ms2; P <.05) and in normalized units (P <.05). In subjects with CHF but not in controls, it also significantly increased the low frequency to high frequency ratio (from 1.3 +/- 0.12 to 1.89 +/- 0.16; P <.001) and low frequency expressed in normalized units (P <.05). Sildenafil citrate caused no significant changes in the QT interval or dispersion.


CONCLUSIONS
These findings indicate that, in men with heart failure, sildenafil citrate reduces vagal modulation and increases sympathetic modulation, probably through its reflex vasodilatory action. The autonomic system changes induced with sildenafil citrate could alter QT dynamics. Both changes could favor the onset of lethal ventricular arrhythmias. At the dose usually taken for erectile dysfunction, sildenafil citrate has no direct effect on cardiac repolarization (QT interval or dispersion).
Piccirillo
Gianfranco
G
Dipartimento di Scienze, dell-Invecchiamento, I Clinica Medica, Policlinico Umberto I, Rome, Italy. piccirillog@uniroma1.it .
Nocco
Marialuce
M
Lionetti
Marco
M
Moisè
Antonio
A
Naso
Camilla
C
Marigliano
Vincenzo
V
Cacciafesta
Mauro
M
D000284:Administration, Oral; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D016022:Case-Control Studies; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011687:Purines; D000068677:Sildenafil Citrate; D016037:Single-Blind Method; D013450:Sulfones; D013599:Systole / Q000187:drug effects / Q000502:physiology
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate