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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myocardial ischemia-reperfusion injury occurs in a wide spectrum of patients, ranging from survivors of out-of-hospital cardiac arrest to acute myocardial infarction victims as well as patients undergoing cardiac surgery, and represents a major public health burden. This injury contributes significantly to morbidity and mortality, despite meticulous adherence to presently known principles of myocardial protection. Despite the considerable progress that has been made in the field of myocardial protection, high-risk subsets of patients continue to exhibit ischemia-reperfusion-related complications, including prolonged contractile dysfunction (stunning), low-output syndrome, perioperative myocardial infarction, and cardiac failure, requiring prolonged intensive care. Sildenafil, a phosphodiesterase 5 inhibitor, currently licensed for the treatment of erectile dysfunction and pulmonary hypertension has shown great promise in animal studies as a possible pharmacologic agent for cardioprotection. This review article discusses the pharmacology of sildenafil and focuses on the available evidence from animal studies on the potential role of sildenafil for treating ischemia-reperfusion injury with its implications for clinical practice.
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PMID:Cardioprotection with sildenafil: implications for clinical practice. 1716 4

Nitric oxide (nitrogen monoxide) (NO) plays an important role in a wide range of physiologic processes. A major mediator of endothelial function, NO regulates vasodilatory and antithrombotic actions in the vasculature and plays a role in reproductive functions, bronchodilation, bone formation, memory, insulin sensitivity, and gastrointestinal relaxation. NO is formed from NO synthase. Impaired NO bioactivity is strongly associated with endothelial dysfunction and cardiovascular disease, but is also implicated in a broad range of other disorders, including pulmonary hypertension, insulin resistance, erectile dysfunction, and preeclampsia. Numerous therapies designed to target NO are being investigated and developed, including NO donors and stimulants. The recent African-American Heart Failure Trial (A-HeFT) showed that the NO donor isosorbide dinitrate, combined with the vasodilator hydralazine, significantly reduced morbidity and mortality in black patients with moderate-to-severe heart failure. Antihypertensive drugs, including angiotensin-converting enzyme inhibitors, calcium channel blockers, and third-generation beta-blockers, are NO stimulants that have demonstrated significant improvement of endothelial function and NO bioactivity. Other cardiovascular therapies that may improve NO bioactivity include statins, l-arginine, and nonpharmacologic approaches such as exercise and dietary changes.
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PMID:Aspects of nitric oxide in health and disease: a focus on hypertension and cardiovascular disease. 1717 Jun 2

During the past 18 years, sildenafil has evolved from a potential anti-angina drug to an on-demand treatment for erectile dysfunction and more recently to a new orally active treatment for pulmonary hypertension. Recent studies suggest that the drug has powerful cardioprotective effect against ischemia/reperfusion injury, doxorubicin-induced cardiomyopathy and anti-hypertensive effect induced by chronic inhibition of nitric oxide synthase in animals. Based on several recent basic and clinical studies, it is clear that sildenafil and other clinically approved type-5 phosphodiesterase-5 inhibitors including vardenafil and tadalafil will eventually be developed for several cardiovascular indications including essential hypertension, endothelial dysfunction, ischemia/reperfusion injury, myocardial infarction, ventricular remodeling and heart failure.
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PMID:Cardiovascular protection with sildenafil following chronic inhibition of nitric oxide synthase. 1724 65

Erectile dysfunction (ED) is related to cardiovascular risk factors by an impairment of endothelial function. Therefore, symptoms of ED are probably to precede cardiovascular disease and events. Moreover, endothelial dysfunction is common in patients with decreased left ventricular ejection fraction (LVEF). Hence, left ventricular dysfunction probably results in a decreased erectile function. A total of 192 cardiovascular high-risk patients from the EROSS Programme (Evaluation of Role of Sexual Dysfunction in the Saarland Programme) were evaluated regarding onset and severity of ED using the IIEF-5 questionnaire. LVEF was measured with magnetic resonance imaging, angiographically or echocardiographically. Prevalence of ED was 80.6%. Patients with moderate or severe impairment of ejection fraction had a significant increase of ED (p = 0.001). Multivariate analysis identified LV dysfunction as an independent risk factor for ED independent of heart failure symptoms (p = 0.001). Moreover, symptoms of ED appeared 3.04 +/- 7.2 years prior to the cardiovascular event (p = 0.005). LVEF is an independent risk factor for the development or increase of ED in cardiovascular high-risk patients, probably caused by an impairment of endothelial function. Hence, ED is suggested to be an early symptom of generalised cardiovascular disease and events. Thus, cardiovascular evaluation is recommended in patients with ED providing the opportunity of optimised preventional treatment.
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PMID:Erectile dysfunction correlates with left ventricular function and precedes cardiovascular events in cardiovascular high-risk patients. 1731 96

Sexual dysfunction is a common problem of increasing incidence that is associated with multiple co-morbid conditions and chronic diseases. In heart failure, however, exact numbers are unknown, in part secondary to under-reporting and under-interrogating by health care providers. A gender-specific questionnaire was modified from established sexual dysfunction questionnaires to correspond to a non-randomized outpatient heart failure population, to assess the prevalence and demographic distribution of sexual dysfunction and potential treatments expectations. One-hundred patients in a stable hemodynamic condition in New York Heart Association classes I-III participated. Eighty-seven percent of women were diagnosed with female sexual dysfunction compared to 84% of men with erectile dysfunction. Eighty percent of women reported reduced lubrication, which resulted in frequent unsuccessful intercourse in 76%. Thirty-six percent of patients thought that sexual activity could harm their current cardiac condition; 75% of females and 60% of men stated that no physicians ever asked about potential sexual problems. Fifty-two percent of men considered sexual activity in their current condition as an essential aspect of quality of life and 61% were interested in treatment to improve sexual function. Sexual dysfunction appears to be high in prevalence in both men and women with chronic compensated heart failure and represents a reduction in quality of life for most. Despite the fact that most patients are interested in receiving therapy to improve sexual dysfunction, treatment options are rarely discussed or initiated.
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PMID:The prevalence and clinical relevance of sexual dysfunction in women and men with chronic heart failure. 1788 30

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.
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PMID:Sexual activity and chronic heart failure. 1790 27

Between 25,000 and 75,000 new cases of angina refractory to maximal medical therapy and standard coronary revascularization procedures are diagnosed each year. In addition, heart failure also places an enormous burden on the U.S. health care system, with an estimated economic impact ranging from $20 billion to more than $50 billion per year. The technique of counterpulsation, studied for almost one-half century now, is considered a safe, highly beneficial, low-cost, noninvasive treatment for these angina patients, and now for heart failure patients as well. Recent evidence suggests that enhanced external counterpulsation (EECP) therapy may improve symptoms and decrease long-term morbidity via more than 1 mechanism, including improvement in endothelial function, promotion of collateralization, enhancement of ventricular function, improvement in oxygen consumption (VO2), regression of atherosclerosis, and peripheral training effects similar to exercise. Numerous clinical trials in the last 2 decades have shown EECP therapy to be safe and effective for patients with refractory angina with a clinical response rate averaging 70% to 80%, which is sustained up to 5 years. It is not only safe in patients with coexisting heart failure, but also is shown to improve quality of life and exercise capacity and to improve left ventricular function long-term. Interestingly, EECP therapy has been studied for various potential uses other than heart disease, such as restless leg syndrome, sudden deafness, hepatorenal syndrome, erectile dysfunction, and so on. This review summarizes the current evidence for its use in stable angina and heart failure and its future directions.
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PMID:Enhanced external counterpulsation and future directions: step beyond medical management for patients with angina and heart failure. 1793 50

Phosphodiesterase type 5A (PDE5A) selectively hydrolyzes cyclic GMP. Inhibitors of PDE5A such as sildenafil are widely used to treat erectile dysfunction, but growing evidence supports important roles for the enzyme in both the vasculature and heart. In disorders such as cardiac failure, PDE5A upregulation may contribute to a decline in cGMP and protein kinase G signaling, exacerbating dysfunction. PDE5A plays an important role in the pulmonary vasculature where its inhibition benefits patients with pulmonary hypertension. In the heart, PDE5A signaling appears compartmentalized, and its inhibition is cardioprotective against ischemia-reperfusion and antracycline toxicity, blunts acute adrenergic contractile stimulation, and can suppress chronic hypertrophy and dysfunction attributable to pressure-overload. In this review, we discuss the molecular biology, pharmacology, and physiology of PDE5A, mechanisms of vascular and cardiac regulation, and recent evidence supporting the utility of selective PDE5A inhibition for the treatment of cardiovascular disorders.
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PMID:Phosphodiesterase type 5: expanding roles in cardiovascular regulation. 1804 25

Cardiovascular risk is determined by multiple risk factors. Blockade of the renin-angiotensin system is an important approach to the prevention of cardiovascular events. In the largest angiotensin receptor blocker cardiovascular outcome study to date, the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) program will compare the efficacy of therapy with telmisartan and ramipril, in reducing cardiovascular events in patients at high risk (history of coronary artery disease, stroke or transient ischemic attack, peripheral artery disease, or diabetes with evidence of end-organ damage). Recruited patients (n = 31,546) will be followed up for a period of 6 years, and more than 150,000 patient-years of data will be recorded. The primary endpoint is a composite of cardiovascular death, stroke, acute myocardial infarction, and hospitalization for congestive heart failure; secondary endpoints focus on reductions in newly diagnosed heart failure, new-onset type 2 diabetes, cognitive decline, atrial fibrillation, and nephropathy. In addition, an ambulatory blood pressure monitoring substudy will be conducted to assess the effect of treatment on endpoints after adjustment for 24-hour blood pressure values. Other substudies of the treatment effects on erectile dysfunction, blood markers, arterial stiffness, oral glucose tolerance, and the progression of target organ damage are also planned. The results of the ONTARGET program are due in 2008, and the findings are expected to have important clinical implications for the management of patients at high cardiovascular risk.
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PMID:Cardiac and vascular protection: the potential of ONTARGET. 1844 80

Most patients with chronic heart failure (CHF) can safely engage in sexual activity and be treated for erectile dysfunction with sildenafil, provided that they do not have active coronary ischemia and do not require treatment with nitrates. Clinicians should know the physiological requirements for sexual activity and the impact chronic heart failure has on sexual performance. Fear of cardiac events during intercourse can interfere with patients' ability to perform and enjoy sex, and thus, it is important that the physician be able to counsel patients with chronic heart failure about sexual activity.
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PMID:[Heart failure and sexual dysfunction]. 1847 42


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