Sexual Activity and Chronic Heart Failure
2007; Elsevier BV; Volume: 82; Issue: 10 Linguagem: Inglês
10.4065/82.10.1203
ISSN1942-5546
AutoresStacy A. Mandras, Patricia A. Uber, Mandeep R. Mehra,
Tópico(s)Urinary Bladder and Prostate Research
ResumoLittle has been published about sexual function in chronic heart failure (CHF) and knowledge among clinicians in this regard is sparse. To review data regarding sexual function and dysfunction in patients with CHF, 2 of the authors (S.A.M. and P.A.U.) independently conducted a literature search using the MEDLINE database. English-language articles and cited bibliographies published between January 1996 and November 2006 were reviewed. Search terms included heart failure or CHF or ventricular dysfunction or heart disease in conjunction with sexual activity, erectile dysfunction, impotence, or sex. Articles were selected for inclusion if they had a primary focus on CHF and sexual function or dysfunction. Critical reviews of the literature, observational studies using self-reported patient surveys, and prospective, blinded, randomized, placebo-controlled trials were included. Articles were not excluded on the basis of patient sample size but were excluded if the article concerned a broad aspect of cardiovascular disease rather than CHF. When properly screened and treated, most patients with CHF can safely engage in sexual activity and be treated for erectile dysfunction with sildenafil, provided that they do not have active ischemia and do not require treatment with nitrates. Clinicians should know the physiological requirements of sexual activity and the impact CHF has on sexual performance. Fear of a cardiac event during intercourse can interfere with patients' ability to perform and enjoy sex, and so it is important that the physician be able to counsel patients with CHF about sexual activity. Little has been published about sexual function in chronic heart failure (CHF) and knowledge among clinicians in this regard is sparse. To review data regarding sexual function and dysfunction in patients with CHF, 2 of the authors (S.A.M. and P.A.U.) independently conducted a literature search using the MEDLINE database. English-language articles and cited bibliographies published between January 1996 and November 2006 were reviewed. Search terms included heart failure or CHF or ventricular dysfunction or heart disease in conjunction with sexual activity, erectile dysfunction, impotence, or sex. Articles were selected for inclusion if they had a primary focus on CHF and sexual function or dysfunction. Critical reviews of the literature, observational studies using self-reported patient surveys, and prospective, blinded, randomized, placebo-controlled trials were included. Articles were not excluded on the basis of patient sample size but were excluded if the article concerned a broad aspect of cardiovascular disease rather than CHF. When properly screened and treated, most patients with CHF can safely engage in sexual activity and be treated for erectile dysfunction with sildenafil, provided that they do not have active ischemia and do not require treatment with nitrates. Clinicians should know the physiological requirements of sexual activity and the impact CHF has on sexual performance. Fear of a cardiac event during intercourse can interfere with patients' ability to perform and enjoy sex, and so it is important that the physician be able to counsel patients with CHF about sexual activity. The physiological effects and clinical aspects of sexual function have been extensively studied and reported in patients who have angina or who have experienced a myocardial infarction1DeBusk RF Sexual activity in patients with angina.JAMA. 2003; 290: 3129-3132Crossref PubMed Scopus (36) Google Scholar, 2Hellerstein HK Friedman EH Sexual activity in the postcoronary patient.Arch Intern Med. 1970; 125: 987-999Crossref PubMed Scopus (198) Google Scholar, 3Muller JE Mittleman MA Maclure M Sherwood JB Tofler GH Triggering myocardial infarction by sexual activity: low absolute risk and prevention by regular physical activity: determinants of Myocardial Infarction Onset Study Investigators.JAMA. 1996; 275: 1405-1409Crossref PubMed Google Scholar, 4Kimmel SE Sex and myocardial infarction: an epidemiologic perspective.Am J Cardiol. 2000; 86: 10F-13FAbstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar, 5Jackson G Sexual intercourse and stable angina pectoris.Am J Cardiol. 2000; 86: 35F-37FAbstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar and in those who have undergone coronary artery bypass graft surgery6Johnston BL Cantwell JD Watt EW Fletcher GF Sexual activity in exercising patients after myocardial infarction and revascularization.Heart Lung. 1978; 7: 1026-1031PubMed Google Scholar or heart transplant.7Mulligan T Sheehan H Hanrahan J Sexual function after heart transplantation.J Heart Lung Transplant. 1991; 10: 125-128PubMed Google Scholar However, less has been published about sexual function in patients with chronic heart failure (CHF), and clinicians are therefore less well informed on this topic. The purpose of this review is to provide clinicians with a succinct knowledge base regarding sexual activity in CHF. We first review the hemodynamics of sexual activity in normal physiological states and in CHF. Second, we examine the relationship between erectile dysfunction (ED) and CHF and explore the use of phosphodiesterase inhibitors and alternative therapies to treat ED in these patients. Third, we develop an approach that the clinician can use in counseling patients with CHF regarding sexual activity. Finally, the article touches briefly on gaps in the literature and areas for future study. Two authors (S.A.M. and P.A.U.) independently conducted a literature search by using the MEDLINE database. English-language articles and cited bibliographies published between January 1996 and November 2006 were reviewed. Search terms included heart failure or CHF or ventricular dysfunction or heart disease in conjunction with sexual activity, erectile dysfunction, impotence, or sex. Articles were selected for inclusion if they had a primary focus on CHF and sexual function or dysfunction. Critical reviews of the literature were included, as were observational studies using self-reported patient surveys, and prospective, blinded, randomized, placebo-controlled trials. Articles were not excluded on the basis of patient sample size but were excluded if the article focused on a broad aspect of cardiovascular disease rather than on CHF. Sexual activity consists of 4 stages: baseline resting, foreplay, stimulation, and orgasm. In young healthy couples, heart rate (HR) and blood pressure (BP) increase modestly during each stage; peak coital HRs occur during orgasm and range between 140 and 180 beats/min, with a mean increase in systolic BP of 80 mm Hg and in diastolic BP of 50 mm Hg.8Bohlen JG Held JP Sanderson MO Patterson RP Heart rate, rate-pressure product, and oxygen uptake during four sexual activities.Arch Intern Med. 1984; 144: 1745-1748Crossref PubMed Scopus (182) Google Scholar, 9Masters WH Johnson VE Human Sexual Response. Little, Brown and Co, Boston, MA1966Google Scholar, 10Nemec ED Mansfield L Kennedy JW Heart rate and blood pressure responses during sexual activity in normal males.Am Heart J. 1976; 92: 274-277Abstract Full Text PDF PubMed Scopus (111) Google Scholar Respiratory rates and tidal volumes also markedly increase. In a study that investigated the hemodynamic parameters during sexual activity of middle-aged men with or without coronary artery disease at home using 24-hour ambulatory electrocardiographic monitors, the mean HR at the time of orgasm was 117.4 beats/min, with a mean BP of 162/89 mm Hg.2Hellerstein HK Friedman EH Sexual activity in the postcoronary patient.Arch Intern Med. 1970; 125: 987-999Crossref PubMed Scopus (198) Google Scholar Interestingly, the peak coital HRs were submaximal, lower than those found during the patients' normal daily activities (mean, 120 beats/min). Minute oxygen consumption has also been measured during sexual activity and is expressed as metabolic equivalent tasks (METs) (1 MET is defined as the energy expended at rest, which is equivalent to body oxygen consumption of 3.5 mL/kg/min).8Bohlen JG Held JP Sanderson MO Patterson RP Heart rate, rate-pressure product, and oxygen uptake during four sexual activities.Arch Intern Med. 1984; 144: 1745-1748Crossref PubMed Scopus (182) Google Scholar In a study by Bohlen et al,8Bohlen JG Held JP Sanderson MO Patterson RP Heart rate, rate-pressure product, and oxygen uptake during four sexual activities.Arch Intern Med. 1984; 144: 1745-1748Crossref PubMed Scopus (182) Google Scholar self- and partner stimulation required 1.7 and 1.8 METs, respectively, whereas coitus required 2.5 METs with the "woman-on-top" and 3.3 METs with the "man-on-top." During coitus, peak HRs and maximal oxygen consumption were maintained for approximately 15 seconds. To put these measurements into perspective, 2.0 to 3.0 METs represent the energy expended walking on level ground at 2 to 2.5 mph or doing light housework (dusting) and 3.0 to 4.0 METs that expended while walking on level ground at 3 to 4 mph, climbing stairs slowly, or doing general housework (vacuuming).7Mulligan T Sheehan H Hanrahan J Sexual function after heart transplantation.J Heart Lung Transplant. 1991; 10: 125-128PubMed Google Scholar By comparison, sexual activity requires 2.0 to 3.0 METs in the preorgasmic stage and 3.0 to 4.0 METs during orgasm.8Bohlen JG Held JP Sanderson MO Patterson RP Heart rate, rate-pressure product, and oxygen uptake during four sexual activities.Arch Intern Med. 1984; 144: 1745-1748Crossref PubMed Scopus (182) Google Scholar However, contrasting hemodynamic results were reported in a middle-aged man with severe CHF due to ischemic cardiomyopathy and pulmonary hypertension.11Cremers B Kjellstrom B Sudkamp M Bohm M Hemodynamic monitoring during sexual intercourse and physical exercise in a patient with chronic heart failure and pulmonary hypertension [letter].Am J Med. 2002; 112: 428-430Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar As measured by an implanted ambulatory hemodynamic monitor, his HR increased during physical exercise (brisk walking) to parallel his level of activity (HR increased from 70 to 105 beats/min; right ventricular pressures, from 50 to 74 mm Hg systolic and from 10 to 13 mm Hg diastolic; and pulmonary artery diastolic pressure, from 28 to 35 mm Hg). During sexual activity, the patient's HR increased only minimally during the preorgasmic phase but increased rapidly at orgasm, peaking at 131 beats/min (vs 53 beats/min before foreplay). A marked increase in right ventricular pressure, from 38/8 to 101/21 mmHg, and a corresponding doubling in diastolic pulmonary pressures were also observed. This difference can likely be explained by activation of the sympathetic nervous system and the influence of psychological or emotional factors (arousal, fear, anxiety) in the patient with CHF during sexual activity. The American Heart Association has estimated that more than 4.9 million people in the United States have CHF.12American Heart Association Heart Disease and Stroke Statistics-2005 Update. American Heart Association, Dallas, TX2005Google Scholar As CHF progresses, patients experience an increase in fatigue, shortness of breath, palpitations, or angina, decreasing their quality of life and potentially interfering with their ability to perform sexually. Jaarsma et al13Jaarsma T Dracup K Walden J Stevenson LW Sexual function in patients with advanced heart failure.Heart Lung. 1996; 25: 262-270Abstract Full Text PDF PubMed Scopus (125) Google Scholar studied 62 patients (men, 82%; women, 18%) with New York Heart Association (NYHA) functional class III and IV CHF to determine the effect of low ejection fraction (EF) on sexual interest, sexual function, and marital relationships. A 6-minute walk test was used to determine the exercise tolerance of the patients and echocardiography to measure their EF. Sexual function was assessed using the self-reported sexual adjustment scale. Most patients (73%) reported a marked or complete loss in sexual interest. Sexual activity markedly decreased or ceased in 76%. More than half of the patients reported a reduction in the level of satisfaction they experienced during sex, and 58% reported frequent or complete inability to perform sexually because of CHF. Interestingly, whereas a meaningful association was found between patients' scores on the sexual adjustment scale and their symptom severity as ascertained from their history and their exercise tolerance on the 6-minute walk test, no such association between EF and sexual function was observed. This finding is consistent with prior studies, which showed that exercise capacity in CHF is related not to resting EF but rather to increased HR and stroke volume in the face of abnormal preload response, autonomic dysregulation, and increased vascular resistance.14Meiler SEL Ashton JJ Moeschberger ML Unverferth DV Leier CV An analysis of the determinants of exercise performance in congestive heart failure.Am Heart J. 1987; 113: 1207-1217Abstract Full Text PDF PubMed Scopus (53) Google Scholar, 15Fransciosa JA Park M Levine TB Lack of correlation between exercise capacity and indexes of resting left ventricular performance in heart failure.Am J Cardiol. 1981; 47: 33-39Abstract Full Text PDF PubMed Scopus (796) Google Scholar Subsequently, Westlake et al16Westlake C Dracup K Walden JA Fonarow G Sexuality of patients with advanced heart failure and their spouses or partners.J Heart Lung Transplant. 1999; 18: 1133-1138Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar reported similar results in a study of 63 patients with CHF (men, 69.4%) and their spouses. In this study, most patients (62%) reported that their frequency of sex had slightly or markedly decreased, 30% that they had stopped having sex, 22% that they had no interest in sex, and 59% that they had had slight or constant problems performing. Little has been published to guide clinicians in counseling their patients with CHF about sexual function. In a review article about intimacy needs and chronic illness, Steinke17Steinke EE Intimacy needs and chronic illness: strategies for sexual counseling and self-management.J Gerontol Nurs. 2005; 31: 40-50PubMed Google Scholar suggests advising patients with CHF to use a "semi-reclining or on-bottom" position during coitus, which decreases the level of physical exertion, and to stop and rest if dyspnea occurs. She recommends encouraging foreplay because it allows the patient and the partner to determine the patient's exercise tolerance and to express affection if exercise capacity is so diminished that more strenuous activities are not physically possible. Erectile dysfunction affects 60% to 70% of CHF outpatients.18Bocchi EA Guimaraes G Mocelin A Bacal F Bellotti G Ramires JF Sildenafil effects on exercise, neurohormonal activation, and erectile dysfunction in congestive heart failure: a double-blind, placebo-controlled, randomized study followed by a prospective treatment for erectile dysfunction.Circulation. 2002; 106: 1097-1103Crossref PubMed Scopus (162) Google Scholar Patients with CHF often use tobacco, are obese, and have hypertension, diabetes mellitus, coronary artery disease, or hyperlipidemia; other predisposing factors for ED include polypharmacy and depression.19Webster LJ Michelakis ED Davis T Archer SL Use of sildenafil for safe improvement of erectile function and quality of life in men with New York Heart Association Classes II and III congestive heart failure: a prospective, placebo-controlled, double-blind crossover trial.Arch Intern Med. 2004; 164: 514-520Crossref PubMed Scopus (76) Google Scholar Erectile dysfunction, cardiovascular disease, and depression seem to form a mutually reinforcing triad20Goldstein I The mutually reinforcing triad of depressive symptoms, cardiovascular disease, and erectile dysfunction.Am J Cardiol. 2000; 86: 41F-45FAbstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar; ED is caused by and can itself cause depression, as does CHF when patients become symptomatic and have reduced quality of life. Rastogi et al21Rastogi S Rodriguez JJ Kapur V Schwarz ER Why do patients with heart failure suffer from erectile dysfunction? a critical review and suggestions on how to approach this problem.Int J Impot Res. 2005; 17: S25-S36Crossref PubMed Scopus (47) Google Scholar explored why patients with CHF develop ED, concluding that multiple factors may be involved. In addition to the decreased exercise capacity mentioned previously, patients with CHF have arterial compliance abnormalities and often atherosclerosis, which reduces blood flow into the penile corpora cavernosa. Furthermore, endothelial dysfunction either decreases the production or increases the breakdown of nitric oxide, a powerful vasodilator that promotes penile engorgement by relaxing the penile chambers.22Schwarz ER Rodriguez J Sex and the heart.Int J Impot Res. 2005; 17: S4-S6Crossref PubMed Scopus (31) Google Scholar Elevated levels of circulating endothelin and other potent vasoconstrictors are also observed in patients with CHF and interfere with their ability to achieve and maintain an erection. Erectile dysfunction can be caused or worsened by many of the medications that are commonly prescribed for the treatment of CHF, including digoxin, β-blockers, diuretics, and spironolactone.21Rastogi S Rodriguez JJ Kapur V Schwarz ER Why do patients with heart failure suffer from erectile dysfunction? a critical review and suggestions on how to approach this problem.Int J Impot Res. 2005; 17: S25-S36Crossref PubMed Scopus (47) Google Scholar Interestingly, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers appear to favorably affect sexual function. Currently, insufficient data exist to evaluate the effect of biventricular pacemakers and cardiac resynchronization therapy on sexual function. The treatment of ED in patients with CHF begins with optimization of CHF management.21Rastogi S Rodriguez JJ Kapur V Schwarz ER Why do patients with heart failure suffer from erectile dysfunction? a critical review and suggestions on how to approach this problem.Int J Impot Res. 2005; 17: S25-S36Crossref PubMed Scopus (47) Google Scholar Sexual function improves as CHF symptoms are reduced and exercise capacity increases. Rastogi et al21Rastogi S Rodriguez JJ Kapur V Schwarz ER Why do patients with heart failure suffer from erectile dysfunction? a critical review and suggestions on how to approach this problem.Int J Impot Res. 2005; 17: S25-S36Crossref PubMed Scopus (47) Google Scholar recommend avoiding when possible drugs such as digoxin and thiazide diuretics which can contribute to ED. They also recommend replacing the peripherally acting propranolol with metoprolol or carvedilol (which has the added benefit of α-blockade) and replacing spironolactone with the more selective mineralocorticoid receptor antagonist eplerenone. These recommendations have not been studied in randomized trials, and few patients with CHF are currently treated with propranolol. The mainstay of pharmacological therapy for ED is a class of drugs known as phosphodiesterase-5 inhibitors, which includes sildenafil, vardenafil, and tadalafil. The drugs work by inhibiting the breakdown of cyclic guanosine monophosphate, a second messenger of prostacyclin and nitric oxide, resulting in relaxation of the smooth muscle of the corpora cavernosa, increased blood flow to the penis (vasodilation), and better erection. In a recent review on ED in CHF, Schwarz et al23Schwarz ER Rastogi S Kapur V Sulemanjee N Rodriguez JJ Erectile dysfunction in heart failure patients.J Am Coll Cardiol. 2006 Sep 19; 48 (Epub 2006 Aug 28.): 1111-1119Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar comprehensively discussed the underlying mechanisms of these drugs. All 3 drugs appear to be equally effective in the treatment of ED; however, the newer drugs, vardanafil and tadalafil, have not been as well studied and therefore fewer data are available regarding their safety in patients with CHF.20Goldstein I The mutually reinforcing triad of depressive symptoms, cardiovascular disease, and erectile dysfunction.Am J Cardiol. 2000; 86: 41F-45FAbstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar However, Ghofrani et al24Ghofrani HA Voswinckel R Reichenberger F et al.Differences in hemodynamic and oxygenation responses to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension: a randomized prospective study.J Am Coll Cardiol. 2004; 44: 1488-1496PubMed Google Scholar compared the hemodynamic profiles of the 3 drugs in patients with pulmonary arterial hypertension, showing that the drugs differ in time to peak hemodynamic effect, pulmonary selectivity, and effect on arterial oxygenation. In the most recent consensus statement of the American College of Cardiology and American Heart Association, CHF is a relative contraindication for the use of sildenafil.25Cheitlin MD Hutter Jr, AM Brindis RG et al.Use of sildenafil (Viagra) in patients with cardiovascular disease [published correction appears in Circulation 2000;101(23):2389].Circulation. 1999; 99: 168-177Crossref PubMed Scopus (275) Google Scholar Concern has been raised that patients with CHF who take both vasodilators and sildenafil are at risk for profound hypotension. Webster et al19Webster LJ Michelakis ED Davis T Archer SL Use of sildenafil for safe improvement of erectile function and quality of life in men with New York Heart Association Classes II and III congestive heart failure: a prospective, placebo-controlled, double-blind crossover trial.Arch Intern Med. 2004; 164: 514-520Crossref PubMed Scopus (76) Google Scholar studied sildenafil use in 35 patients with NYHA class II or III CHF in a placebo-controlled randomized and blinded crossover trial. Patients were included if they did not use nitrates, had a history of chronic ED, and had negative stress test results. They were randomized to either 6 weeks of placebo with a switch to 6 weeks of 50 mg of sildenafil, or the reverse. The patients, who were asked to keep a diary on the use of the drug, were followed up at 2-week intervals to assess for adverse effects of the drug and symptoms of CHF exacerbation. The patients also completed questionnaires that were designed to elicit information regarding erectile function, symptoms of depression, or perceptions of CHF symptoms. No significant change in HR or BP was observed with sildenafil use, and erectile function significantly improved when patients were taking sildenafil vs placebo. When taking sildenafil, patients also experienced a decrease in depressive symptoms and an increase in quality of life. No major hemodynamic events occurred during the study. All patients were successfully treated with diuretics as outpatients, and none reported any of the adverse effects that are common with sildenafil use. In a fixed-dose, double-blind, randomized, placebo-controlled, 2-way crossover study, Bocchi et al18Bocchi EA Guimaraes G Mocelin A Bacal F Bellotti G Ramires JF Sildenafil effects on exercise, neurohormonal activation, and erectile dysfunction in congestive heart failure: a double-blind, placebo-controlled, randomized study followed by a prospective treatment for erectile dysfunction.Circulation. 2002; 106: 1097-1103Crossref PubMed Scopus (162) Google Scholar evaluated the efficacy and safety of sildenafil in 23 male patients with CHF, as well as its effects on exercise and neurohormonal activation. To assess safety, patients were randomized to receive either 50 mg of sildenafil or placebo before undergoing a 6-minute walk test and then a maximal exercise test. The next day, the patients crossed over to the second treatment and repeated the protocol. Those who tolerated the drug were advanced to phase 2, an open-label, home-based, prospective study in which patients took a flexible dose of 25 mg to 150 mg of sildenafil (dose was determined on the basis of efficacy and adverse effects) 1 to 2 hours before sexual activity and then recorded the drug's efficacy using the 15-question International Index of Erectile Function. In the safety phase of the study, sildenafil reduced HR at rest, during the 6-minute walk test, and until the 8th minute of the maximal exercise test. In addition, mean ± SD resting systolic BP decreased from 116±18 to 108±18 (P=.004); diastolic BP, from 69±9 to 63±11 (P<.05). During the exercise phase, sildenafil reduced the mismatch between pulmonary ventilation and perfusion while also increasing peak oxygen consumption and exercise time. No difference was found in plasma norepinephrine levels between the sildenafil and placebo groups. This study showed that sildenafil was well tolerated and that it led to an improvement in most of the patient's scores on the International Index of Erectile Function. The effective mean ± SD dose for erection was 58±30 mg, with efficacy rates similar to those in prior studies (between 62% and 83%).26Goldstein I Lue TF Padma-Nathan H Rosen RC Steers WD Wicker PA, Sildenafil Study Group Oral sildenafil in the treatment of erectile dysfunction [published correction appears in N Engl J Med. 1998;339(1):59].N Engl J Med. 1998; 338: 1397-1404Crossref PubMed Scopus (2034) Google Scholar More recently, Katz et al27Katz SD Parker JD Glasser DB et al.Efficacy and safety of sildenafil citrate in men with erectile dysfunction and chronic heart failure.Am J Cardiol. 2005; 95: 36-42Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar performed a multicenter, prospective, randomized, double-blind, placebo-controlled, flexible-dose study to investigate the efficacy and tolerability of sildenafil in patients with stable CHF. Patients were included if they had a known EF of 40% or less, stable symptoms for 4 weeks or more, no signs of congestion on examination, stable oral drug regimen without nitrate use for 4 weeks or more, and no CHF-related emergency department or inpatient hospital visits for 3 months or more. Most patients in the study had mild CHF, although approximately 10% in both groups had class III CHF. The patients, who ranged in age from 37 years to 83 years, included those with comorbid conditions (diabetes mellitus, hyperlipidemia, hypertension, ischemic heart disease, previous coronary bypass surgery). Patients were excluded if they used nitrates, were at high cardiovascular risk, or had hypotension, uncontrolled hypertension, hypertrophic or restrictive cardiomyopathy, primary uncorrected severe valvular heart disease, a history of myocarditis, or recent implantable defibrillator firing. Significant improvements in erectile function, sexual desire, and both intercourse and overall satisfaction were seen in the sildenafil vs placebo group. More than 90% of the adverse effects of the drug were transient and of mild to moderate severity; they included headache, facial flushing, and chromatopsia. Few cardiovascular adverse events occurred in either group. Some cases of sudden cardiac death have been reported in men with coronary artery disease who used sildenafil.28Kostis JB Jackson G Rosen R et al.Sexual dysfunction and cardiac risk (the second Princeton Consensus Conference).Am J Cardiol. 2005; 96: 313-321Abstract Full Text Full Text PDF PubMed Scopus (183) Google Scholar In vitro, sildenafil has been noted to block the rapid component of the delayed rectifier potassium current in a dose-dependent fashion. It therefore has the potential to act as a class III antiarrhythmic drug at high plasma concentrations. Piccirillo et al29Piccirillo G Nocco M Lionetti M et al.Effects of sildenafil citrate (Viagra) on cardiac repolarization and on autonomic control in subjects with chronic heart failure.Am Heart J. 2002; 143: 703-710Abstract Full Text PDF PubMed Scopus (47) Google Scholar investigated the effects of sildenafil on cardiac repolarization in men with NYHA class II CHF, with the hypothesis that patients with an altered phase would be at higher risk for drug-induced QT prolongation, which leads to malignant arrhythmia and sudden cardiac death. In this study, 10 men with ischemic dilated cardiomyopathy and 10 healthy controls received a single dose of 50 mg of sildenafil at rest. Measurements were then taken of the QT intervals and dispersion as well as of dynamic variables such as the slope of the line drawn when QT is plotted against HR and the index of QT variability. Spectral analysis of HR and BP variability was also performed to measure changes in autonomic cardiovascular control after sildenafil administration. With respect to the measurements of the QT intervals, the baseline mean QT was significantly longer in the patients with CHF than in controls, reflecting CHF-related structural changes in the heart such as hypertrophy and dilatation; however, overlap was observed for variance in QT in patients with CHF and controls. In patients with CHF who took sildenafil, the QT interval and QT dispersion remained unchanged, but both the QT variance and the QT-RR slope increased. Sildenafil significantly lowered mean ± SD systolic BP in both groups (107±3 to 100±2 mm Hg, with sildenafil; 112±2 to 103±2 mm Hg, for controls; P<.05) and slightly reduced diastolic BP in the controls but not in the patients with CHF. Mean ± SD HR also increased in both groups with sildenafil (by 13%±3% in the CHF group and 8%±3% in the control group [P<.05]). The mild systemic vasodilatory effects were well tolerated by both groups; none of the men had adverse reactions to sildenafil. The increase in HR may be attributable to a reflex decrease in sinus vagal activity and/or an increase in sympathetic modulation. These autonomic changes, not blockage of the potassium channel, were also thought to be responsible for the changes in QT variance and QT-RR slope. The changes in the
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