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Keywords:

  • beta-blockers;
  • erectile dysfunction;
  • heart failure;
  • medical therapy

Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Sexual activity in heart failure
  5. Summary and conclusion
  6. References

Heart failure (HF) is a complex clinical syndrome with a constantly increasing incidence and prevalence in western countries. Total absence of sexual activity is registered in 30% of HF patients. Moreover, HF-induced reduction in exercise tolerance, side effects of HF medications and the coexistence of shared risk factors between HF and sexual dysfunction may further aggravate the sexual health of HF patients. The purpose of this review is to examine the pathophysiological mechanisms behind the association of erectile dysfunction (ED) and HF, the potential therapeutic approaches and the eventual indications for sexual activity in HF patients. Medline and Cochrane Library search was performed from January 1970 through October 2012 to retrieve relevant papers outlining the association between ED and HF. Many evidences have outlined a tight association between ED and HF pathophysiological standpoint. Shared risk factors, common pathogenic traits and epidemiologic association represent some of the links between these conditions. Erectile dysfunction has been recognized as an earlier predictor of cardiovascular events; moreover, HF itself may cause and/or worsen ED because of its particular feature and co-morbidities. Furthermore, some cardiovascular drugs may contribute to impaired erectile function. In stable patients with stable HF, sexual activity is generally not contraindicated but it should be encouraged, as a form of moderate-intensity physical exertion. An effective treatment of ED in HF patients should be founded on the correction of reversible risk factors, on the choice of cardiovascular drugs with the lowest effect upon patient's erectile function, and on the use of phosphodiesterase-5-inhibitors. Physicians should be aware of the close relation between HF and ED and of the related clinical and therapeutic implications, in order to improve patients quality of life and clinical outcome.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Sexual activity in heart failure
  5. Summary and conclusion
  6. References

Heart failure (HF) is a complex clinical syndrome that may result from any structural or functional cardiac disorder impairing the ability of the heart to fill with or eject blood. Incidence and prevalence of HF are constantly increasing, due to improved management of coronary disease and increased life length expectancy. In western countries, HF prevalence ranges between 1 and 2%, and it is expected to double in the next 30 years (Rosamond et al., 2008). The Framingham study demonstrated a direct correlation between age and incidence of HF, along with a greater prevalence in men than in women (Cowie et al., 1999).

Heart failure is secondary to ischaemic heart disease and idiopathic dilated cardiomyopathy in 60% and in 20% of patients, respectively. Valvular defects, hypertension and other causes account for the remaining cases. Typical HF manifestations include peripheral venous congestion, reduction in exercise tolerance and dyspnoea, which systematically lead to quality of life (QoL) impairment.

Among the different aspects contributing to the definition of QoL, sexual activity has certainly a place of paramount importance. Many studies (Schwarz et al., 2006, 2008; Hebert et al., 2008, 2009) have demonstrated the strong impact of HF on sexual health, depending both on psychological and physical factors. Patients concern about the potential risk inherent to sexual activity leads to total absence of sexual activity in 30% of HF patients (Bocchi et al., 2002). Moreover, HF-induced reduction in exercise tolerance, side effects of HF medications and the coexistence of shared risk factors (Drory et al., 1998, 2000; Feldman et al., 2000) between HF and sexual dysfunction may further aggravate the sexual health of HF patients. In fact, ED and HF share several risk factors and pathogenetic mechanisms (Jackson et al., 2010).

We sought to review the pathophysiological mechanisms behind the association of ED and HF, the potential therapeutic approaches and the eventual indications and contraindications for sexual activity in HF patients. Literature search was performed to retrieve relevant papers outlining the association between ED and HF. Medline and Cochrane library was searched from January 1970 through October 2012, using the following keywords: ‘heart failure’, ‘cardiovascular diseases’, ‘erectile dysfunction’, ‘sexual dysfunction’, ‘endothelial dysfunction’. The reference lists of the identified publications were reviewed for additional references.

Erectile dysfunction and heart failure

A significant association between ED and cardiovascular diseases (CVD) has been confirmed in many studies, meta-analysis, reviews and consensus conferences (Kostis et al., 2005; Rastogi et al., 2005; Jackson et al., 2010). In this context, published data evidence an increased prevalence of ED, and sexual dysfunction as a whole, in cardiovascular patients, and, vice versa, an increased prevalence of CVD in patients with ED (Guo et al., 2010); overall, men with ED share numerous comorbid conditions with those subjects with cardiovascular disorders (Laumann et al., 1999). Rosen et al. (2004), for instance, showed a significantly higher prevalence of hypertension, angina, high cholesterol, diabetes and depression in men with ED as compared with men with normal erectile function. This association correlates with an increased prevalence of ED in cardiovascular patients. Indeed, patients experiencing acute coronary syndromes or undergoing cardiac revascularization often report a decrease in their sexual activity due to impaired erectile function and decreased libido (Lai et al., 2011). Psychological factors also play a significant role, since patients may be afraid of triggering new cardiovascular events during sexual activity. At present, ED has even been proposed as an early predictor of coronary artery disease (CAD) (Thompson et al., 2005; Riedner et al., 2011); in this context, a number of data evidence how ED could anticipate CAD manifestation up to 3 years in advance (Montorsi et al., 2006; Hodges et al., 2007). Among the different CVD manifestations, a particular correlation between HF and ED has been also highlighted. Overall, a growing body of evidence shows that patients with cardiovascular risk factors complaining of ED should also undergo a comprehensive cardiological evaluation. Montorsi et al. found that cardiovascular symptoms were preceded by ED in almost 70% of patients, preceding angina and cardiovascular events of 2–3 and of 3–5 years, respectively (Montorsi et al., 2003). Schouten et al. (2008) evaluated 7945 men aged 50–70. They showed that ED is prospectively associated with CVD, with a hazard ratio [HR] of 1.6 (95% CI: 1.2–2.3) for reduced erectile rigidity and 2.6 (95% confidence interval (CI): 1.3–5.2) for severely reduced erectile rigidity. Baumhäkel & Böhm (2007) showed that left ventricular dysfunction is an independent risk factor for ED, unrelated to severity of HF symptoms (p = 0.001). In addition, ED manifestation preceded cardiovascular events by 3 years. The ONTARGET/TRANSCEND trial demonstrated that ED could be a potent independent predictor of all-cause death (HR 1.84, 95% CI: HR 1.21–2.81, p = 0.005) and of the composite end point of cardiovascular death, myocardial infarction, stroke and HF in men with cardiovascular diseases (HR 1.42, 95% CI: 1.04–1.94, p = 0.029) (Böhm et al., 2010). A recent cohort study by Apostolo et al. has shown a strong correlation between ED and HF. Indeed, investigators found an ED prevalence of 69.3% in patient with HF. Moreover, in the subgroup of patients with ischaemic HF, ED prevalence raised up to 81.1% (Apostolo et al., 2009). These data appear even stronger when compared with prevalence of ED in the general population: the Second Princeton Consensus Conference actually estimated an ED prevalence of 50% in 60 year old men (Kostis et al., 2005). In the same study, evaluating 101 HF patients, multivariate regression has established a link between diabetes mellitus, anaemia and ED among HF patients. No association between ED and left ventricular ejection fraction, natriuretic peptide levels or chronic renal failure has been proven.

Table 1. Common risk factors, markers and associate conditions for cardiovascular disease and erectile dysfunction
Risk factorsPathophysiologyReferences
Age

Impaired endothelial NO bioavailability

Impaired microvascular function (age-associated changes in microvessel function are uncertain but may involve alterations in NO, prostanoid, endothelium-derived hyperpolarizing factor and endothelin-1 pathways)

Associated CAD risk factors

Laumann et al. (1999), Walsh (2009), Hannan et al. (2010)
Hypertension

Left ventricular hypertrophy

Heart failure

Myocardial ischaemia

Endothelial dysfunction

Atherosclerosis

Aneurysm formation

Burchardt et al. (2000), Giuliano et al. (2004), Hannan et al. (2011)
Dyslipidaemia

Impaired endothelial function

Atheromatous lesion formation

Fung et al. (2004), Solomon et al. (2006), Jackson et al. (2010), Huang et al. (2010), Raman et al. (2011)
Diabetes mellitus type II

Impaired endothelial function

Atherogenesis

Abnormalities in apoprotein and lipoprotein particle distribution

Glycosylation and advanced glycation end-products (AGE) in plasma and arterial wall

‘Glycoxidation’ and oxidation

Procoagulant state

Insulin-resistance and hyperinsulinemia

Hormone-, growth-factor- and cytokine-enhanced smooth muscle cell proliferation and foam cell formation

Peripheral neuropathy

Pyorala et al. (1998), Piatti et al. (2000), Desouza et al. (2002), Potenza et al. (2009), Batty et al. (2010)
Smoking

Impaired endothelial function

Arterial stiffness

Bocchi et al. (2002), Rosen et al. (2004)
Overweight

Imbalance between endothelium-derived vasoactive factors favoring vasoconstriction

Endothelial inflammation

Bocchi et al. (2002), Piatti et al. (2003a,b), Corona et al. (2010a,b), Toque et al. (2011), Barton et al. (2012)
Sedentary lifestyle

Loss in central arterial compliance

Metabolic dysfunction (increased plasma triglyceride levels, decreased levels of high-density lipoprotein -HDL- cholesterol, and decreased insulin sensitivity; reduction of lipoprotein lipase –LPL- activity)

Impaired reactive hyperaemia (ameasure of peripheral vascular function)

Influence of mood

Derby et al. (2000), Hamburg et al. (2007), Jackson et al. (2010), Nualnim et al. (2011)
Depression

Reduced adherence to medical prescription (medications and life style modifications)

Greater platelet activation and aggregation

Endothelial dysfunction

Impaired autonomic dysfunction (lower heart rate variability)

Psychogenic

Bandini et al. (2010), Serrano et al. (2011)
Alcohol

Alcoholic cardiomyopathy

Hypertension

Changes in heart rate variability (HRV) (acute consumption) HRV is defined as fluctuations in inter-beat interval length which reflect the heart's response to extra-cardiac factors that affect heart rateHRV allows simultaneous assessment of both sympathetic and parasympathetic activity and the interplay between them

Inhibition of hypothalamo-pituitary-testes axis

Impaired serum testosterone level

Decline of smooth muscle, choline acetyltransferase and NO synthase in the penis

Klatsky et al. (1977), Diamond (1989), Jackson et al. (2006a,b), Kam et al. (2010)
MarkersPathophysiologyReferences
Testosterone deficiency

Induces metabolic syndrome

Veno-occlusive dysfunction

Stellato et al. (2000), Laaksonen et al. (2005), Corona et al. (2010a,b)
Markers of endothelial dysfunctionImpaired endothelial function and inflammationLibby et al. (1995), Reape & Groot (1999), Ferri et al. (1999), Bocchio et al. (2004), Hansson et al. (2006), Zouaoui Boudjeltia et al. (2007)
Associated conditionsPathophysiologyReferences
Metabolic syndrome

Abdominal obesity: adiponectin has both vascular and metabolic actions, and may contribute importantly to the connection between metabolism and vascular dysfunction

Hyperlipidemia (see above)

Glucose intolerance (see above)

Hypertension(see above)

Insulin restistance is associated with impaired endothelium-dependent vasodilation and, specifically, with impaired insulin-stimulated vasodilation

Bocchi et al. (2002), Esposito et al. (2005), Kupelian et al. (2006), Vlachopoulos et al. (2007), Suetomi et al. (2008), Pohjantahti-Maaroos & Palomaki (2011)
Chronic Inflammation

Atherosclerotic disease initiation and progression

Atherothrombosis

Prediction of future clinical events: Acute coronary syndrome, following revascularization procedures

Osman et al. (2006), Urbonaviciene et al. (2012)
Obstructive sleep apnoea (OSA)

Oxidative stress-induced endothelial dysfunction

OSA causes pulmonary vasoconstriction, bradycardia, and decreased cardiac output, with regional cerebral and myocardial vasodilation to preserve oxygen delivery to these critical organs

Cardiac contractility and diastolic relaxation may be directly impaired by cyclic hypoxaemia in OSA

Sympathetic activation

Insulin resistanceHypertension

Severe OSA itself may contribute directly to LV diastolic dysfunction

Somers et al. (1995), Atkeson et al. (2009), Lavie (2009), Budweiser et al. (2009), Szymanski et al. (2011)

Erectile dysfunction and heart failure risk factors

Erectile dysfunction and Heart failure are tightly associated to the same risk factors (Table 1) (Laumann et al., 1999; Fung et al., 2004). These include both not modifiable conditions, such as ageing (Bacon et al., 2003) and modifiable conditions, such as obesity, altered lipid profile, hypertension and diabetes mellitus (Grover et al., 2006). Recreational habits, for instance cigarette smoking, yield a strong unfavourable impact on both conditions, as evidenced by the FAMHES trial (Wu et al., 2011). This study evaluated 2 686 men, aged 20–79, with a 1-year follow-up. Data adjusted for age, alcohol drinking, physical activity, hypertension, diabetes, dyslipidemia and obesity, showed a significantly increased risk of ED in smokers (namely, more than 20 cigarettes die) than in non-smokers (odds ratio = 1.23; 95% CI: 1.03–1.49; p = 0.02). Consistently with these findings, improving cardiac risk factors profile in mid-life may decrease the risk of ED as well as CVD in old age (Fung et al., 2004).

Endothelial dysfunction has been suggested as the potential common pathophysiological mechanism underlying ED, CVDs, diabetes and metabolic syndrome (Vlachopoulos et al., 2008). At present, there is a general agreement on the fundamental role of endothelial dysfunction in the development and progression of cardiovascular and metabolic diseases (Davignon & Ganz, 2004), and the role of endothelium in penile erectile function has also been extensively discussed (Solomon et al., 2003; Costa & Virag, 2009; Averbeck et al., 2012).

Erection physiology: the case for endothelial dysfunction

The acquisition and maintenance of penile erection is primarily a vascular phenomenon, triggered by neural signals and facilitated by the presence of appropriate hormonal and psychological conditions. Nitric oxide (NO) plays a fundamental role in maximizing arterial blood flow and penile engorgement by acting as a local neurotransmitter, facilitating the relaxation of intracavernosal trabeculae (Gratzke et al., 2010). High levels of intrapenile NO are necessary for normal erectile function. Nitric oxide is synthesized in the endothelial cells from citrulline and oxygen by the nitric oxide synthase (NOS) enzyme. In patients with endothelial dysfunction, this process becomes inefficient (Wu et al., 2011). In fact, endothelium is an active biological tissue, which constantly secretes metabolic factors. Any injuring condition, like atherosclerosis or metabolic unbalances, leads to a reduction in endothelial function (Piatti et al., 2000, 2003a,b), which is characterized by an impaired synthesis and an increased NO degradation, and to an increased permeability of the endothelium to plasma constituents. Clearly, endothelial dysfunction reduces penile erection, because of the physiopathological mechanisms discussed above (Costa & Virag, 2009) and on this ground, many authors have recently focused on the need to consider endothelial function assessment as a fundamental step in evaluating ED (Tamler & Bar-Chama, 2008). The macroscopic effects of endothelial dysfunction could be evidenced by decreased arterial dilation in response to different stimuli, such as adenosine or acetylcholine infusion or shear stress. In particular, in normal vessels shear stress induces the so called ‘flow-mediated vasodilation’ (FMD), which can be measured by echo Doppler imaging of the brachial artery before and after an ischaemic stimuli. The ischaemia-induced vasodilation is an index of vasomotor function and permits to estimate endothelial function.

Role of endothelial dysfunction in heart failure

Heart failure is a complex syndrome associated to several metabolic imbalances (e.g. increased production of oxygen free radicals, increased rest energy expenditure, altered glucose tolerance). Additionally, peripheral blood supply reduction contributes to worsen all pathological conditions mentioned above and vice versa, leading to a vicious circle of HF progression and impairment of the patient general conditions. Reduction in NO availability due to impaired endothelial NOS activity and subsequent impairment in vascular dilation causes a decrease in blood flow and oxygen supply, favouring free oxygen radical production. This inflammatory substrate favours myocardial fibrosis and progressive loss of contractile function, leading to left ventricular remodelling and dilation (Torre-Amione et al., 1996). Endothelial dysfunction is also linked with atherosclerosis development and progression, facilitating cholesterol deposition in the intimal wall. The endothelial lesion is not confined to coronary vessels, but it generally involves the whole organism. In fact, in presence of impaired endothelial function, inflammation blood markers, such as TNF-alfa, interleukin-1, -6 and -18, are consistently raised. These markers are released from endothelium, circulating monocytes and platelets but also from lungs, liver and the failing heart itself (Yndestad et al., 2006). The response to medical treatment may depend on different effects on the inflammatory state (Alfieri et al., 2008; Fragasso et al., 2013).

Metabolic syndrome is defined as the contemporary presence of raised triglycerides, reduced HDL cholesterol, raised blood pressure and raised fasting plasma glucose. Metabolic syndrome, as shown by Rosen et al. (2004), is highly prevalent in patients with ED and in patients with HF. As for other vascular conditions, endothelial dysfunction is one of the pathophysiological mainstays of metabolic syndrome (Piatti et al., 2000). The clinical implications of the pathophysiological components of the metabolic syndrome on erectile and cardiac function have been previously discussed across the manuscript.

Causes of erectile dysfunction in heart failure patients

Many factors contribute to the onset and progression of ED, and most of them are predominant in HF patients. Moreover, those factors are strongly connected, so usually they co-exist and potentiate each other. Causes of ED in HF patients include endothelial dysfunction, atherosclerosis, exercise tolerance reduction, cardiac drugs, psychogenic factors and HF related hypogonadism.

  • Endothelial dysfunction. This pathological condition is strongly associated with HF and may reduce NO production and vascular dilation, which are fundamental steps throughout the penile erection process (Piatti et al., 2000; Costa & Virag, 2009).
  • Atherosclerosis, which emerges as one of the main cause of HF by determining myocardial ischaemia and necrosis, but it may also induce penis blood flow impairment (Hodges et al., 2007).
  • Exercise tolerance impairment. Depending on the severity of heart function, HF patients experience various degrees of reduction in exercise tolerance, ranging from limitation on physical exertion to limitation on basic activities of daily living. Therefore, although the physical effort related to sexual activity is relatively modest (Thorson, 2003), some HF patients, especially those in NYHA class III–IV, cannot afford it. Energy expenditure of sexual intercourse will be discussed across the manuscript, along with the correlation between HF stage and prevalence and severity of ED.
  • Cardiac pharmacological treatment: due to their intrinsic multiple vascular, metabolic and neuro-humoral effects, many cardiovascular drugs are known to exert a negative effect upon erectile function (Grimm et al., 1997; Karavitakis et al., 2011). Different and specific effects of CV drugs will be further discussed.
  • Anabolic deficiency: metabolic imbalance is a typical feature of HF patients and leads to increase catabolism and cardiac cachexia. Anabolic hormones, including insulin-like growth factor-1 (IGF-1), dehydroepiandrosterone sulphate (DHEA-S) and total testosterone (TT), enhance exercise tolerance in healthy men. Reduction of those hormones leads to reduction in exercise capacity. Many studies demonstrate the increased prevalence of anabolic deficiency in HF. Jankowska et al. evaluated 208 HF patients and found TT and DHEA-S levels inversely related to NYHA class, regardless of HF aetiology (all < 0.01) (Jankowska et al., 2009). Moreover, anabolic deficiency is independently associated with increased mortality and hospitalization in men with HF (Wehr et al., 2011). Obviously, very important clinical manifestations of anabolic deficiency and hypogonadism are ED and reduced libido. These data suggest that anabolic deficiency may exert a twofold negative effect on sexual function, reducing exercise tolerance and decreasing penile function and libido.
  • Psychogenic factors are very relevant in both conditions. HF patients often suffer from depression, a condition known to decrease libido and impair erectile function. Major depression is associated to a decrease in pleasure, concentration, sex drive, sleep and appetite. Gottlieb et al. (2004) demonstrated a linear correlation between the extent of depression and the severity of functional limitation in 155 HF patients. Depression, associated to concern about cardiac health may induce performance anxiety, which increases sympathetic tone and arteriolar constriction, finally decreasing penis blood flow.

Cardiac drugs and erectile dysfunction

Many cardiac drugs may be implicated in the development of ED. A major role has been suggested for thiazide diuretics, beta blockers and lipid-lowering drugs.

Thiazide diuretics

Thiazide diuretics are commonly used to unload HF patients, in association with loop diuretics, especially when the latter do not achieve the desired diuretic effect. These drugs are also often prescribed among hypertensive patients, especially after the JNC VII, which indicated them as the first line therapy for uncomplicated hypertension (Chobanian et al., 2003). However, they have been associated to ED in a number of studies. In the Treatment of Mild Hypertension Study (TOMHS) (Grimm et al., 1997) a higher incidence of ED has been reported at 2 years in patients treated with chlorthalidone compared with the placebo group. These results probably depend on the vascular and metabolic abnormalities caused by these drugs, including endothelial dysfunction and increased vascular oxidative stress (Zhou et al., 2008), hyperlipidemia (Lithell, 1991), insulin resistance (Ferrari et al., 1991), new onset diabetes mellitus (Eriksson et al., 2008; Gupta et al., 2008), and stimulation of the sympathetic (Grassi et al., 2003) and renin–angiotensin–aldosterone (RAAS) systems Burnier & Brunner (1992). In the ALLHAT study a higher incidence of type 2 diabetes was observed in the thiazide-treated group compared with the other treatment groups (Whelton et al., 2005).

Beta blockers

Beta blockers (BB) are a mainstay of HF therapy, with a therapeutic efficacy which does not only rely on heart rate reduction alone (Fragasso et al., 2008). Conversely, their role in contributing to ED is still controversial. Indeed, BB have been suspected to be an important cause of ED (Croog et al., 1986), depending on their adverse metabolic effects and on increased peripheral vascular resistance and arteriolar tone, but a systematic review of randomized, controlled trials found only a small increase in risk of sexual dysfunction with beta blocker therapy (5 per 1 000 patients treated) (Ko et al., 2002). The key of the problem lies in the different effects exerted by different BB, depending on their pharmacologic and ancillary properties profile. First and second generation BB (e.g. propranolol and atenolol) are well-known to reduce sexual function. The link between early generation BB and ED could be found in some central nervous system effects (for those hydrophilic molecules passing the hematoencephalic membrane) and in worsening endothelial function, eventually contributing to arteriolar vasoconstriction. Additionally, first generations BB have been consistently shown to adversely affect lipid metabolism (Eliasson et al., 1981). In contrast, third generation BB have been shown to be devoid of detrimental effects on erectile function and metabolic parameters. In this context, many studies have focused on nebivolol, a third generation selective β1-blocker, lacking of intrinsic sympathomimetic activity, which has a unique haemodynamic profile. Indeed nebivolol is the only BB able to modulate endothelial NO system (Dessy et al., 2005), by increasing the availability of endothelial NO. This effect results in coronary and systemic vasodilation and, thereby, in peripheral resistance reduction and counteraction of endothelial dysfunction. This effect of restoring endothelial function has recently been tested on penile function, outlining that treatment with nebivolol may significantly potentiate erectile response both in diabetic and non-diabetic rats, regardless of its effects on blood pressure. It also improved response to sildenafil in diabetic rats, completely reversing ED after sildenafil administration (Angulo et al., 2010). In a study evaluating 48 hypertensive patients nebivolol, as compared with metoprolol, played a significantly greater beneficial effect on erectile function. Nebivolol administration also correlated with an increase in orgasmic function, sexual desire and intercourse satisfaction, while none of these effects was observed with metoprolol (Brixius et al., 2007). Furthermore, Doumas et al. evaluated 44 hypertensive men treated with atenolol, metoprolol or bisoprolol. 29 (65.9%) of these patients suffered from baseline ED. After at least 6-months BB treatment, all patients were switched to nebivolol. After 3 months, 20 out of 29 (69%) patients reported a significant improvement in erectile function and in 11 out of these 20, erectile function was even normalized (Doumas et al., 2006). Blood pressure control was as satisfactory as with other BB in all patients. These data confirm the optimal profile of nebivolol in the context of ED. Moreover, results of the SENIORS study showed efficacy and safety of nebivolol in the setting of chronic HF in patients older than 70 (Flather et al., 2005), and nebivolol is currently registered in most European countries (but not in the USA) for HF therapy. On this basis nebivolol can be considered as an efficient option in patients older than 70 that experienced ED. However, since no data from randomized controlled trials have pointed out the safety and efficacy of nebivolol in the settings of HF in patients younger than 70, further studies are needed to better focus this issue.

Lipid-lowering drugs

Considering that HF is mostly a consequence of ischaemic heart disease, lipid lowering drugs, in particular statins, emerge as a mandatory therapy in most patients with HF. Hyperlipidemia is also considered a significant risk factor for ED, being the only active risk factor in up to 42% of patients (Doğru et al., 2008). Saltzman et al. (2004) demonstrated that atorvastatin alone could lead to an improvement in erectile function in men with hypercholesterolaemia as the only risk factor for ED. This study does not clarify if the improvement in erectile function was directly related to reduction in cholesterol levels and/or to the pleiotropic, non-lipidic effects of statins. Studies in rats and diabetic mice show that atorvastatin or rosuvastatin can ameliorate endothelial function in corpora cavernosa and also ameliorate sildenafil responsiveness (Miner & Billups, 2008). Results in humans are still controversial. A placebo-controlled randomized trial in 12 men who were non-responders to sildenafil suggested that atorvastatin improved sexual function and the response to sildenafil (Herrmann et al., 2006). A larger trial in 131 men also showed that atorvastin can ameliorate responsiveness to sildenafil, especially in those patients who have moderate to severe ED. None of these patients regained normal, unassisted erectile function (Dadkhah et al., 2010).

On the other hand, other studies have shown the occurrence of ED with statins and fibrate therapy (Bruckert et al., 1996; de Graaf et al., 2004). ED associated with simvastatin usage has also been reported by the French Pharmacovigilance System Database (Do et al., 2009). In addition, Solomon et al. (2006) reported that statin therapy in patients at high-risk for CVD may lead to further deterioration of ED. Therefore, the risk of ED induced by statins should also be considered in some cases.

In conclusion, statins effects on ED are potentially positive but still not fully understood. Further investigations are needed to determine if statin administration by itself could ameliorate erectile function and phosphodiesterase type 5 inhibitors (PDE5Is) responsiveness in treated patients, as well.

Sexual activity in heart failure

  1. Top of page
  2. Summary
  3. Introduction
  4. Sexual activity in heart failure
  5. Summary and conclusion
  6. References

Cardiac patients are often concerned about potential triggering of myocardial events during sexual intercourse and, as a consequence, they might have sex less frequently or they may abstain at all. Additionally, their physicians often do not have adequate knowledge of the issue and sometimes they do suggest to reduce sexual activity, by default. Actually, moderate physical exercise is not contraindicated in stable HF, but it is indeed recommended. In fact, the reduction in exercise tolerance experienced by many HF patients leads to a progressive reduction in daily activities. Restriction of activity promotes physical deconditioning, which may adversely affect clinical status and contribute to the exercise intolerance of patients with HF, creating a vicious circle of deconditioning and exercise intolerance. In addition, low left ventricular ejection fraction typical of HF plays a key role in the reduction of exercise capacity and, as a consequence, of sexual activity in patients with HF.

Functional impairment in HF is mainly characterized by fatigue, dyspnoea and development of peripheral oedema. Since symptoms severity is directly correlated with heart function impairment, the most widely used clinical classification of HF is the New York Heart Association (NYHA) classification, which defines four functional classes (Table 2).

Table 2. New York Heart Association functional classification of heart failure
NYHA ClassSeverity based on symptoms and physical activity
NYHA INo limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, or dyspnoea
NYAH IISlight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnoea
NYAH IIIMarked limitation of physical activity. Comfortable at rest, but less than ordinary activity results in fatigue, palpitation, or dyspnoea
NYAH IVUnable to carry on any physical activity without discomfort. Symptoms at rest. If any physical activity is undertaken, discomfort is increased

A direct correlation between HF severity and ED has been also demonstrated. Apostolo et al. showed a direct correlation between NYHA HF classification and prevalence and severity of ED, assessed by the International Index of Erectile Function (IIEF): the rate of patients with normal or mildly impaired erectile function decreased from 70 to 50%, 10% and to almost 0% in NYHA I, NYHA II, and NYHA IV, respectively (Apostolo et al., 2009). On the other side, the prevalence of moderate to severe ED increased from 25% in NYHA to 90% in NYHA IV patients. According to these data, cardiopulmonary testing was performed in all study patients and showed a reverse correlation between ED severity and peak oxygen consumption (VO2) (the maximal oxygen uptake during exercise, with a normal value of ≥20 mL/min/kg). Peak VO2 is known to have a strong linear correlation with both cardiac output and muscular blood flow (Reddy et al., 1988) and it is a predictor of cardiovascular events. Peak VO2 is reduced in HF, with an inverse relation with NYHA class, averaging around 10 mL/min/kg in the most severe cases. Assuming that sexual activity requires, during the orgasmic phase, a VO2 between 10 and 14 mL/min/kg, investigators found that in 10/29 patients with peakVO2 between 10 and 14 mL/min/kg there was a normal or slightly reduced sexual performance, while none of the individuals with peakVO2 <10 mL/min/kg reported a normal sexual function (Apostolo et al., 2009). Interestingly enough, regardless of the presence of HF, level of sexual function appears to have a significant link with the 6 min walking test (6MWT) (Jaarsma et al., 1996). In the 6MWT the patient is asked to walk for six minutes at the maximum speed on a pre-measured distance, usually a hospital corridor. Global distance is then measured and provides an estimate of exercise capacity. Peripheral oxygen saturation is also measured and at the end of the test a questionnaire is administered to evaluate physical exertion capacity.

In this context, many studies in HF patients have demonstrated the safety and efficacy of physical exercise on symptoms reduction and QoL improvement. There is general agreement on the beneficial effects exerted by aerobic exercise training in HF patients, as outlined by ACC/AHA guidelines (Jessup et al., 2009). In fact, regular physical exercise increases peak VO2 (Belardinelli et al., 1996), improves muscle energetic metabolism and gas exchange, reduces fatigue, reduces sympathetic tone and increases vagal tone at rest, thereby restoring autonomic cardiovascular control towards normal (Roveda et al., 2003). Moreover, physical exercise reduces neurohumoral activity, lowering resting levels of aldosterone, vasopressin and natriuretic peptide, reduces inflammatory cytokines and improves endothelial function (Braith et al., 1999; Adamopoulos et al., 2002). Aerobic exercise also improves hemodynamic, since it lowers peripheral vascular resistance (Hambrecht et al., 2000a,b) and improves left ventricle ejection fraction (Haykowsky et al., 2007). Consistently with those evidences, exercise training has been shown to reduce hospitalization and improve survival in HF patients. The HF-ACTION (The Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial was designed to evaluate the efficacy and safety of exercise training in HF patients. A cohort of 2331 NYHA class II to IV patients was randomly assigned to conventional therapy or conventional therapy plus aerobic exercise, with the specific end points to assess all cause mortality and hospitalizations. After adjusting for HF aetiology, the results did not show significant differences, but the analysis demonstrated a relevant decrease in primary end points with the exercise training programme, after stratification for baseline major prognostic factors (Flynn et al., 2009).

Sexual intercourse could be considered a modest exertion, since it averages 2–3 metabolic equivalents (METs) in the pre-orgasm phase and 3–4 METs during orgasm. The MET is a unit of resting oxygen uptake, equivalent to 3.5 mL O2 uptake/kg/min. As an example, 2 METs is the energy expenditure for walking at 3 km/h on ground level; walking at 5 Km/h correspond to 3 METs. Compared with higher-intensity physical exertion, such as cycling at 16 Km/h (6–7 METs) or running on the treadmill (13 METs), the exertion of sexual activity is relatively modest (Thorson, 2003). Furthermore, studies performed in the ‘real-life’ setting showed a peak heart rate of 117 beats per minute (bpm) during sexual intercourse, which was lower than the heart rate during normal daily activities (mean 129 bpm) (Hellerstein & Friedman, 1970). The clinical implication of these observations is that sexual intercourse is associated with a modest increase in myocardial oxygen demand with a peak lasting only a brief period of time.

Clearly, physical exertion is not indicated in every HF patient. The Second Princeton Consensus Conference has developed recommendations for the management of sexual dysfunction in HF patients (Kostis et al., 2005). These guidelines suggest a prior stratification in low-risk (NYHA I), intermediate risk (NYHA II) and high risk (NYHA III–IV) patients. Low-risk patients have no limitation on their sexual activity and do not need further investigations. High-risk patients should be assessed for their cardiac condition before having sexual activity because also mild exercise might decompensate their cardiac status. Intermediate risk patients should be further stratified by exercise testing, echocardiography and 6MWT in high- or low- risk.

Assuming that sexual intercourse is not contraindicated in patients with stable HF, there is still the problem of the highest prevalence of sexual dysfunction in chronic heart failure (CHF) patients to deal with. The management of ED in HF patients should pass across three steps (i) the correction of all modifiable risk factors, (ii) the choice of HF drugs with the best sexual profile, and (iii) the use of PDE5is.

Correction of risk factors

Even though some factors like age or family history could not be modified, an important component of the treatment of sexual dysfunction is the correction of reversible causes, leading to restoration of endothelial function.

There is general agreement on the statement that the severity of ED significantly correlates with the level of exposure to smoking. Cigarette smoking has been correlated to ED independently from the increase in cardiovascular risk (Chew et al., 2009). Mannino et al. (1994) examined 4 462 US Army Vietnam-era veterans aged 31–49 years: of those, 1162 never smoked, while 1 292 were former smokers and 2008 current smokers. Reported prevalence of ED was 3.7% among current smokers, 2.0% among former smokers, and 2.2% among those men who never smoked (p = 0.005). Pourmand et al. (2004) studied 118 former smokers and 163 active smokers, demonstrating that quitting the smoking habit could prevent ED progression and, in 25% of cases, lead to an improvement in ED. Chew et al. (2009) found that former smokers and ever smokers have significantly higher odds of ED as compared with those who never smoked. The mechanism behind this association probably depends on the cigarette smoking-dependent increased prevalence of arterial constriction, with reduction in oxygen supply and increased free oxygen radical production. Cigarette smoking can also induce impairment of endothelial function and reduced NO bioavailability (Tostes et al., 2008). Patterns of ED in former smokers suggest that there may be a latent interval between active smoking and symptomatic ED, involving a process initially triggered by smoking: in fact, odds of ED in former smokers were significantly higher 6–10 years following cessation of smoking than <6 or >10 years (Chew et al., 2009). Another study in 40 smokers with ED undergoing penile colour Duplex ultrasound at baseline and after 24–36 h after smoking cessation demonstrated a significant improvement in end-diastolic velocity and a trend towards an increase in peak systolic velocity trough the penile artery (Sighinolfi et al., 2007), confirming the short term detrimental effects of smoking.

Many studies in rats have demonstrated how regular exercise training could improve ED, either associated to co-morbidities (e.g. diabetes mellitus) or not. Investigators attribute these results to an improvement in vascular response and to the re-establishment of a better balance between NO production and NO inactivation. Specifically, a trial has shown an increase in the expression of penile endothelial (eNOS) and neuronal NOS (nNOS) in old and young trained rats, compared with old and young non-trained rats (Ozbek et al., 2010). A small prospective study on 22 hypertensive men showed an improvement in erectile function after 8 weeks of daily exercise training compared with a sedentary population (Lamina et al., 2009). As previously discussed, lowering blood lipid levels usually yields a positive effect on ED in both the general population and in HF patients. Even if lipid lowering drugs (HGM-CoA reductase inhibitor and fibrate) have been associated to ED (Bruckert et al., 1996; de Graaf et al., 2004), two recent studies demonstrated that statin administration improves response to sildenafil in hypercholesterolaemic men with ED who were not initially responsive to sildenafil (Dadkhah et al., 2010) and that atorvastatin administration may ameliorate response to sildenafil in experimental diabetes (Morelli et al., 2009). Therefore, where indicated, statins can be safely administered in patients with ED. Finally, Khoo et al. (2010) have recently demonstrated an improvement in sexual function associated to a 10% reduction in body weight, both in diabetic and non-diabetic obese patients. In fact, a significant association between weight loss and increase in insulin sensitivity and plasma testosterone levels have been established.

Hypertension is a well-described risk factor for ED. The prevalence of ED is significantly greater among men with hypertension than in the general population. In the Massachusetts Male Ageing Study, the age-adjusted prevalence of complete ED was 15% in patients with treated hypertension and was associated with the duration and severity of hypertension (Feldman et al., 1994).

Pharmacological treatment of heart failure in patients with ED

Many cardiovascular drugs, such as BBs, angiotensin converting enzyme (ACE) inihibitors/angiotensin receptors blockers (ARBs), aldosterone antagonists and statins, have been shown to exert a significant impact upon the prognosis in HF patients (Jessup et al., 2009). This clearly means that withdrawing any of them may be difficult. However, as discussed above, different drugs of the same class can exert slightly different effects on metabolic and vascular function. When using drugs potentially responsible for ED, like BB, clinicians should carefully choose the best molecule to administer for any single patient. As previously outlined, newly developed BB, such as nebivolol, should be preferred.

Other commonly adopted HF drugs, such as ACE-inhibitors and ARBs, yield positive effects on vascular function and, usually, they do not exert negative effects on ED. The Trial on Reversing ENdothelial Dysfunction (TREND) demonstrated that quinalapril improves endothelial function in normotensive patients without CAD, severe hyperlipidemia or evidence of HF (Mancini et al., 1996). Investigators attributed these results to the reduction in the vasospastic effect and free radical generation by angiotensin II and to enhancement of endothelial NO production. Moreover, in a pilot study enalapril showed a positive effect on cavernosal perfusion and erectile function in middle aged patients with atherosclerotic ED (mean age 60 ± 6.8 years) (Speel et al., 2005). In a cross-over study, Fogari et al. (2001) treated 160 hypertensive men without prior sexual dysfunction with carvedilol or valsartan; patients were divided in two groups and assumed placebo for 4 weeks, then carvedilol 50 mg/die or valsartan 80 mg/die for 16 weeks and then, after additional 4 weeks placebo step, switched to the other drug for 16 weeks. The results of this latter trial showed a worsening in erectile function during the carvedilol phase, which was not confirmed during the valsartan period. The results were confirmed by the switch off and showed a full recovery of erectile function during valsartan assumption. Moreover, a study evaluating 3 502 hypertensive patients treated with valsartan 80–160 mg/die showed an improvement in erectile function, orgasmic function and overall satisfaction both in the whole group and in the subgroup of patients previously treated with a different antihypertensive drug (Dusing, 2003).

Regarding the use of aldosterone blocking agents, a negative effect of spironolactone on erectile function has been demonstrated (Loriaux et al. 1976), probably due to the affinity of spironolactone for progesteron receptors. Other drugs of the same class, e.g. eplerenone, which has higher specificity for aldosterone receptors, have been demonstrated to exert no negative effect on sexual function. The Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) (Pitt et al., 2003), was a randomized controlled study evaluating 6 642 HF patients, which showed an equivalence of eplerenone to placebo with respect to the incidence of gynaecomastia and ED. Therefore, when aldosterone antagonism is needed, the new agent eplerenone should be preferred.

Diuretics are very frequently used in HF treatment, although their effect on prognosis is not clear (Jessup et al., 2009). As discussed above, diuretics, especially thiazides, may impair erectile function, probably by worsening metabolic balance (alteration in glucose homeostasis, increasing in LDL and total cholesterol, hypeuricemia) (Ferrari et al., 1991; Lithell, 1991; Eriksson et al., 2008; Gupta et al., 2008; Zhou et al., 2008). Further studies are needed to evaluate the effect of other classes of diuretics, such as loop diuretics, on erectile function. However, while studies on other diuretic agents are lacking, the administration of thiazide diuretics should be avoided in HF patients with sexual dysfunction.

Pharmacological treatment of erectile dysfunction in patients with HF

It has been estimated that over 300 millions of people worldwide will use sildenafil or other phosphodiesterases inhibitors (PDE5i) by 2025 (Ayta et al., 1999), most of them having cardiovascular co-morbidities. PDE5is have been demonstrated to be safe in men with CVD. Risk profile is similar in patients with and without CAD and sildenafil has been shown to be safe even in patients with multi-antihypertensive drug regimens regardless of the classes, although some precautions should be taken in order to minimize drugs-interaction risks (Jackson et al., 2006a,b). The main contraindication to PDE5is is the contemporary use of nitrates that can lead to severe hypotension as a consequence of excessive cGMP accumulation and vasodilation. For this reason guidelines recommend a 24-h time interval between the administration of any NO donor and sildenafil (and vice versa) (Cheitlin et al., 1999); for tadalafil and vardenafil interval should be equal to 48 h. Sildenafil should also be used with caution and started at the lowest dose in patients taking α-blockers to avoid symptomatic hypotension. Similar care should also be taken for mixed α/β-blockers, such as carvedilol and labetalol.

Phophodiesterase type 5 and its isoforms 1, 3 and 4 are expressed in the pulmonary arterial vasculature and they are involved in the regulatory system of pulmonary arterial resistance (Rabe et al., 1993). In details PDE5 seems to be overexpressed in pulmonary hypertensive lung, making PDE5 inhibition an ideal pharmacological target for pulmonary vascular disease (Rhodes et al., 2009). In fact, there are several studies demonstrating safety and efficacy of sildenafil, alone or in combination with iloprost and endothelin receptors antagonists, in the treatment of idiopathic pulmonary hypertension. Administration of sildenafil in patients with symptomatic pulmonary arterial hypertension improves exercise capacity, WHO functional class, and hemodynamics (Wilkens et al., 2001; Galiè et al., 2005). Orally administered sildenafil (commercially termed as Revatio®) is approved for primary pulmonary arterial hypertension at the dosage of 20 mg three times a day.

Secondary pulmonary hypertension is a common finding in patients with congestive HF and it is present in up to 78% of patients. These patients have reduced exercise tolerance and poor prognosis compared with patient without pulmonary hypertension (Ghio et al., 2001). Pulmonary artery pressure (PAP) and right ventricular function are important prognostic factors for patients with left ventricle systolic dysfunction. The effects of PDE5is on pulmonary hemodynamics of HF patients suggest an activity similar to that reported for idiopathic PAH. In patients with left ventricular dysfunction and secondary PAH, 50 mg of sildenafil did not affect systemic blood pressure but improved cardiac output by balanced pulmonary and systemic vasodilation (Lepore et al., 2005). Sildenafil has also been shown to improve stress capacity and quality of life in patients with HF and pulmonary hypertension (Lewis et al., 2007). These effects appear operative even in more advanced HF patients. In this context, Freitas et al. (2009) analysed the acute effects of 100 mg sublingual sildenafil in patients with HF and pulmonary hypertension awaiting a heart transplantation. They observed that sildenafil is an effective and safe alternative as a vasodilator during the PAH reversibility test in patients with heart failure and awaiting a heart transplant.

On this basis, usefulness of PDE5 inhibition in HF has grown rapidly. Further evidence has come from the demonstration of a variety of actions in addition to the effects on pulmonary hemodynamics. Many in vitro and animal studies have provided the interesting demonstration that chronic PDE5-inhibition is effective in the control of important cellular and molecular pathways involved in the morphological and functional changes leading to maladaptive left ventricular remodelling and HF. It appears that sildenafil may exert a direct antyhypertrophic effect on myocytes (Takimoto et al., 2005). Furthermore, sildenafil yields a protective influence on myocytes apoptosis (Das et al., 2005) can reduce ischaemia-reperfusion damage (Salloum et al., 2008). Guazzi et al. (2011) have demonstrated than 50 mg of sildenafil three times a day can sinergically act with ACE-inhibitors and BBs, modulating diastolic function and remodelling of left chambers. Webster et al. (2004) observed that sildenafil can improve QoL, ED and associated depression in patient with chronic stable HF. These evidences of safety and efficacy of sildenafil in patient with HF and ED are encouraging but they need to be confirmed by large randomized controlled trials (Cooper et al., 2012).

Potential additional treatments for HF and ED

Other substances could be effective in treating HF and ED. Considering endothelial dysfunction as a primary pathogenetic factor in both conditions as comprehensively discussed in this review, all drugs able to improve this important regulator of vascular function could, at least theoretically, be beneficial. Among the others, oral arginine administration could play a role. l-Arginine has been shown to successfully restore endothelium-dependent vascular responses in the coronary (Drexler et al., 1991) and peripheral (Creager et al., 1992) arteries of hypercholesterolaemic patients, in patients with microvascular angina pectoris (Egashira et al., 1996; Piatti et al., 2003a,b), congestive heart failure (Koifman et al., 1995; Rector et al., 1996), critical limb ischaemia (Bode-Böger et al., 1996) and CAD associated to reduced monocyte adhesion to endothelial cells (Adams et al., 1997). Furthermore, recent findings revealed that arginine-rich medical food, coupled with therapy, improves vascular function, exercise capacity and QoL in patients with stable angina (Maxwell et al., 2002). Additionally, l-arginine administration has been shown to reverse the hemodynamic and rheological changes caused by acute hyperglycaemia (Giugliano et al., 1997). According to this evidence, l-arginine supplementation could also improve endothelial-dependent vasodilatation in patients with microvascular dysfunction, where endothelial dysfunction has been shown to play a major role (Drexler et al., 1991). A study has also evidenced beneficial effects of medium long-term oral administration of l-arginine on blood pressure control and endothelial function in patients with hypertension and microvascular angina (Palloshi et al., 2004). Anecdotical evidence suggests that arginine could be an effective adjunctive treatment also in HF patients (Hambrecht et al., 2000a,b). By inference, oral arginine could be successfully employed in ED, alone or in combination with 5PDEi, even if clinical evidence of this is still poor (Gentile et al., 2009).

Capsaicin, a natural product of capsicum species (chili pepper – capsicum frutescens), induces reflex coronary vasodilatation by stimulation of vagal C fibres. In experimental studies, capsaicin administration has been shown to evoke the release of calcitonin gene-related peptide (CGRP) (White et al., 1993), a principal transmitter in sensory nerves (Kawasaki et al., 1988), which also acts as one of the most potent endogenous vasodilators yet discovered (Brain et al., 1985). Several endogenous agents and conditions activate cardiac C-fibre afferents, with subsequent local release of CGRP (Hua & Yaksh, 1993). During myocardial ischaemia, C-fibre afferents not only convey the sensation of pain, but there is also a local efferent release of CGRP in the heart (Kallner, 1998). After being released, CGRP causes coronary vasodilatation and attenuates the development of myocyte death (Franco-Cereceda & Liska, 2000), probably through a preconditionig mechanism (Li & Peng, 2002). In animal studies, capsaicin-induced increase in coronary flow and heart rate (Oroszi et al., 1999) and hypotensive effects (Chen et al., 1996) have been shown to be dependent on interplay between CGRP and NO. The results of a preliminary study (Fragasso et al., 2004) have indicated that transdermal administration of capsaicin can improve the ischaemic threshold in a significant proportion of patients with CAD. This improvement is likely depending on an increased availability of NO, as evidenced by the observed augmentation of NO levels at 6 h from capsaicin patches application. CGRP levels did not change in patients showing improved exercise during capsaicin treatment. Rate-pressure product (RPP) was similar between placebo and capsaicin, since the latter determined a decrease of blood pressure balanced by an increase in heart rate, indicating a potential beneficial effect also in patients with HF. On this basis, capsaicine could also play a role in ED. The erectile response to intraurethral infusion of capsaicin has suggested the activation of a reflex arc between urethra and corpora cavernosa (Lazzeri et al., 1994). Further studies are necessary to clarify if this arc is integrated at central nervous system level or it is locally triggered, and if it may have pathophysiologic implications. In summary, whether the popular belief that chilli peppers containing capsaicine could improve erectile function in humans needs focused studies.

Finally, despite cardiac transplantation and implantation of left ventricular assistance devices has improved survival and overall QoL in patients with terminal heart failure, their effects on sexual activity is not clearly defined, depending probably by the individual emotional response to such invasive therapies (Basile et al., 2001; Marcuccilli et al., 2011). Nevertheless, in these patients physical activity is usually encouraged and, as a consequence, sexual activity is not contraindicated.

Summary and conclusion

  1. Top of page
  2. Summary
  3. Introduction
  4. Sexual activity in heart failure
  5. Summary and conclusion
  6. References

Heart failure and erectile dysfunction are two clinical conditions characterized by a constantly increasing prevalence and by a deep impact on patients QoL. Likewise, growing evidences have outlined a tight association between the two conditions, from the pathophysiological standpoint. Shared risk factors, common pathogenic traits and epidemiologic association represent some of the links between these conditions. Erectile dysfunction has been recognized as an earlier predictor of cardiovascular events and cardiovascular death; moreover, HF itself may cause and/or worsen ED because of its particular feature and co-morbidities, ranging from impaired exercise tolerance to psychogenic factors and neurohumoral, metabolic and vascular modification. Furthermore, some cardiovascular drugs may contribute to impaired erectile function.

In stable patients with stable HF, sexual activity is generally not contraindicated; in contrast, it should be encouraged, as a form of moderate-intensity physical exertion. An effective treatment of ED in HF patients is possible and should be founded on the correction of reversible risk factors, on the choice of cardiovascular drugs with either low or even none effect upon patient's erectile function, and on the use of PDE5is. Physicians should be aware of the close relation between HF and ED and of the related clinical and therapeutic implications, in order to improve patients QoL and clinical outcome as well.

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  3. Introduction
  4. Sexual activity in heart failure
  5. Summary and conclusion
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