1. health and fitness
2. disease

International Journal of Impotence Research (2005) 17, S25–S36
& 2005 Nature Publishing Group All rights reserved 0955-9930/05 $30.00
www.nature.com/ijir
Why do patients with heart failure suffer from erectile
dysfunction? A critical review and suggestions on
how to approach this problem
S Rastogi1, JJ Rodriguez1, V Kapur1 and ER Schwarz1*
1
Department of Internal Medicine, Division of Cardiology, The University of Texas Medical Branch (UTMB), Galveston,
Texas, USA
Chronic heart failure (HF) is an increasingly common cardiovascular disorder. The goal of healthcare providers is to optimize quality of life in this population, including sexual health. Up to 75%
of patients with HF report erectile dysfunction (ED). As HF is a condition with distinct physiologic
sequelae, some unique organic and psychological factors contributing to ED in this patient
population have been identified, along with risk factors common to the development of coronary
artery disease, HF and ED. This review describes contributing factors to ED in the setting of HF and
highlights treatment considerations for this distinct patient population.
International Journal of Impotence Research (2005) 17, S25–S36. doi:10.1038/sj.ijir.3901426
Keywords: erectile dysfunction; heart failure; phosphodiesterase inhibitors
Introduction
Erectile dysfunction (ED) is the persistent inability
to achieve and/or maintain a penile erection
sufficient for satisfactory sexual performance.1 Data
from the Massachusetts Male Aging study showed
that 52% of men aged 40–70 y reported some degree
of ED.2 As heart failure is another highly prevalent
condition that shares many risk factors with ED, it
is not surprising that ED and HF frequently occur
concomitantly. In a cohort of 62 male and female
clinic outpatients with HF, approximately threequarters reported compromised libido and ED.3 In
our own patient population, at least 75% of patients
with chronic HF reported ED (unpublished). Interestingly, HF patients place greater importance on
symptomatic improvement and thereby quality of
life, rather than longer survival.4 Sexuality and
a satisfying sexually active life is an important
component of quality of life.5,6
ED and cardiac disease
Numerous studies have shown that ED shares
several modifiable risk factors with cardiovascular
disease including atherosclerosis,7 hypertension,
hyperlipidemia, diabetes mellitus,8 smoking,9 obesity and sedentary lifestyle.10 Table 1 shows the
estimated prevalence of ED in various conditions
including coronary artery disease and in the presence of cardiovascular risk factors. More specific
data are difficult to obtain due to concomitant
presence of more than one risk factor in most of
the patients diagnosed with ED. Data from several
studies involving patients with cardiac disease have
shown a high prevalence, 42–75%, of ED in this
patient population.11–16 Of interest are studies that
have shown a significant correlation between the
presence of vasculogenic ED and clinically evident
or subclinical ischemic heart disease. Kaiser et al7
demonstrated that the presence of arteriogenic ED
(using penile Doppler ultrasonography) was associated with a high prevalence of clinically apparent
atherosclerosis, particularly in men aged 450 y.
Greenstein et al17 also reported a significant
correlation between ED and the number of occluded
coronary arteries. Similar findings were recently
reported by Solomon et al.11 Other investigators
have found incidence rates of occult cardiovascular
disease in men with ED as high as 15–30%.18,19
Causes of ED in patients with heart failure
*Correspondence: ER Schwarz, MD, PhD, FESC, FACC,
FSCAI, Department of Medicine, Division of Cardiology,
The University of Texas Medical Branch (UTMB),
301 University Blvd., 5.106 John Sealy Annex, Galveston,
TX 77555-0553, USA.
E-mail: erschwar@utmb.edu
Patients with heart failure may experience ED for
reasons similar to the general population, and the
etiology may be polyfactoral. However, there are
social, psychological, physiological and drugrelated consequences specific to heart failure that
Why do patients with heart failure suffer from ED?
S Rastogi et al
S26
Table 1 Estimated prevalence of ED in patients with various (cardiovascular) pathologic conditions and/or risks
Condition
Estimated % prevalence
(range) of ED
References
Age (440 y)
33–89
Diabetes mellitus
Hypertension
CAD
20–65
27–68
42–75
Heart failure
Obesity
Hyperlipidemia
Depression
Smoking
Medication
75
Increased
Increased
25–90
Increased
Increased
Feldman et al126; Bai et al127; Safarinejad 128; Chew et al129; Bacon et al130; Morillo
et al131; Moreira et al132; Shiri et al133
McCulloch et al134; Klein et al135; Yamasaki et al136; Alonso et al137; Siu et al138
Burchardt et al139; Jensen et al140; Cuellar et al141
Solomon et al11; Montorsi et al12; Wabrek et al13; Diokno et al14; Dhabuwala et al15;
Kloner et al16
Jaarsma et al3
Esposito and Giugliano142; Esposito et al143; Gunduz et al144
Nikoobakht et al145; Wei et al146; Saltzman et al147
Araujo et al148
Gades et al149; Mannino et al150; Mirone et al151
Derby et al152
a
prevalencea
prevalencea
prevalencea
prevalencea
No definite numbers available.
Table 2 Causes of ED in patients with heart failure
Cause
Mechanism
Arterial insufficiency
Decreased blood flow to the corpus cavernosa due to arterial insufficiency secondary
to atherosclerosis
Inadequate vasodilatory response of the penile vessels and relaxation of trabecular
smooth muscle due to a reduction in the availability of endothelium derived NO
Induce long-lasting contraction of corpus cavernosum and penile vessels. Also serve as
modulators for other contractile agents, enhancing their contractile effect
Loss of libido, increased contraction of corpus cavernosum and penile vessels from
increased sympathetic tone and/or impaired NO release
Decreased sexual function due to decline in exercise capacity due to patient’s inability
to increase heart rate and stroke volume secondary to left ventricle dysfunction and
neurohormonal changes associated with the pathophysiologic state of heart failure
Endothelial dysfunction
ETs
Psychogenic (depression, performance
anxiety)
Cardiac capacity/exercise tolerance
Medication
Beta-adrenergic receptor blockers
Digoxin
Spironolactone (aldosterone antagonist)
Thiazide diuretics
Exact mechanism unclear, decreased perfusion pressure from a direct (unknown) effect
on penile smooth muscle or increased contraction of corporal smooth muscle and vessels
from unopposed alpha-receptor stimulation
Corporal smooth muscle sodium-pump inhibition, which promotes contraction and
impedes NO-induced relaxation
ED and decreased libido secondary to androgen suppression. Primarily a peripheral
anti-androgen effect competing with testosterone and dihydrotestosterone (DHT) for
androgen binding sites. Also, a weak inhibitor of testosterone biosynthesis
Mechanism unknown
may account for the high incidence of ED, and that
warrant specialized consideration. Table 2 summarizes the various causes of ED and their possible
mechanism in patients with HF (Table 3).
Cardiac capacity and exercise tolerance
Sexual activity is closely linked to a patient’s
exercise tolerance and conditioning. While it is
difficult to standardize sexual exertion between
patients and their partners, it is thought that the
‘average’ coitus requires the expenditure of approximately five metabolic equivalents, or roughly the
same amount of oxygen consumption as a brisk walk
International Journal of Impotence Research
up to two flights of stairs.20 Exercise capacity in
chronic HF is determined by a patient’s ability to
increase heart rate and stroke volume beyond a
submaximal stage of exercise.21 In HF, this ability is
disturbed by a lack of preload response, autonomic
dysregulation and excessive vascular resistance,
secondary to neurohormonal activation. Jaarsma
et al3 found a significant relationship between a
patient’s level of sexual function and results of the
6-min walk test. There is also a significant but
weaker link between NYHA functional class and
sexual performance. No significant correlation was
found between sexual function and EF.3 However, in
severely compromised left ventricular function, that
is, patients in NYHA classes 3 and 4, reduced
cardiac capacity might be causing the failure of
Why do patients with heart failure suffer from ED?
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Table 3 Current treatment options for ED in patients with heart failure
Recommendations
Rationale
1. Improve HF:
by implementing ACC/AHA treatment guidelines for HF
in order to improve EF, cardiac capacity, conditioning
2. Assess side effects/replace drugs:
for example, propranolol with metoprolol or carvedilol,
spironolactone with eplerenone, avoid digoxin and
thiazide diuretics, if medically feasible, etc
3. PDE-5 inhibitors:
Improved cardiac capacity and conditioning might help to improve
sexual activity/effort
4. Hormone (replacement) therapy:
5. Other therapy:
(i) intraurethral prostaglandins
(ii) penile prostaglandin injection
(iii) vacuum assist devices
6. Revascularization
(i) angioplasty (PTA)
(ii) surgical revascularization
7. Penile prostheses
Reduced incidence of drug-related impotence and/or decreased libido
Controlled scientific data have demonstrated safety and efficacy of PDE5 inhibitor sildenafil in treatment of ED in patients with heart failure
Benefits seen only in patients with hypogonadism
Patients who are not candidates or fail treatment with PDE-5 inhibitors.
Heart failure per se is not a contraindication, can be safely used in
patients with heart failure as in general population, requires active
compliance and effective in 40–70%
PTA can be considered for focal stenotic lesions in selected patients;
definitive role not established
Surgical revascularization has shown to be beneficial in young patients
without history of diabetes, minimal cardiovascular risk factors and no
corporal veno-occlusive dysfunction, and no large-scale data
Preferable in patients with diffuse vascular disease or impaired
cavernosal function or for those patients who find other treatment
options unsatisfactory, last treatment option, precludes all others
hemodynamic physiology to adequately perform
any physical exertion including satisfactory sexual
intercourse.
Psychological causes
Certainly psychogenic causes of ED such as depression and anxiety may be confounded in HF patients.
This may be primarily due to the belief of a poor
prognosis and the significant impact of cardiac
symptoms in every-day life.22 Depression in this
population is multifactoral,23,24 and fluctuates with
the natural evolution of heart failure symptoms.
Therefore, cardiovascular disease, ED and depression have been proposed to form a mutually
reinforcing triad.25 Performance anxiety and fear of
death during sexual activity also contributes to
ED.26 It is unknown, however, whether treatment
of depression using selective serotonin-reuptake
antagonists improves ED in heart failure patients,
since in particular this class of drug is well known
for its deleterious effects on erectile function and
libido.
Arterial insufficiency
Vasculogenic causes of ED are common, and can be
subdivided into (a) arterial insufficiency and (b)
endothelial dysfunction. As ischemic cardiomyopathy is the most common cause of HF in the United
States, many HF patients have underlying athero-
sclerosis. Atherosclerosis accounts for approximately 40% of ED in men greater than 50 y of age,7
and is at least in part due to reduced arterial inflow
into the penile corpora cavernosa.27 This might be
caused by intimal hyperplasia of the penile vessels,
plaque deposition, focal stenosis or, more frequently, sclerosis, and thus reduced blood flow
through the common iliac and the hypogastric as
well as pudendal arteries.
Endothelial dysfunction
Endothelial dysfunction appears to be a systemic
phenomenon, affecting not only the coronary but
also almost all peripheral circulation. Studies to
establish whether basal nitric oxide (NO) production is altered in HF patients have yielded conflicting results.28–32 One study by Maguire et al33
supports previous observations that NO does not
contribute to basal vascular tone in patients with HF.
It has been suggested that endothelial damage could
result in a reduction in the availability of endothelium-derived NO from either decreased production
or increased breakdown. Decreased production may
be due to mRNA downregulation of the endothelial
enzymes NO synthase and cyclooxygenase, both of
which are required for the production of endothelium-derived vasodilators. This deficiency appears
to be specific to the physiologic state of heart
failure.34 Another hypothesis is that underlying
atherosclerosis alters the L-arginine–NO pathway,
decreasing NO production.35–38 Oxygen-derived free
radicals have also been associated with inhibition of
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Why do patients with heart failure suffer from ED?
S Rastogi et al
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endothelium-dependent vasodilation, suggesting
that rapid inactivation of NO may be caused by
increased free radical production.39 Other possible
mechanisms of endothelial dysfunction include cell
surface receptor abnormalities or alterations at the
G-protein level, which may account for decreased
efficacy of free NO, as seen in atherosclerosis.40
Endothelin elevation
Heart failure is associated with increased circulating
vasoconstrictors such as endothelin (ET),41,42 as
well as a reduction in vasodilators such as prostacyclin.43 ET-1 potently induces slowly developing,
long-lasting contractions in the CC and penile
vessels, and has been suggested to contribute to
the maintenance of corpus cavernosal smooth
muscle tone.44,45 ETs may have important effects
on penile pathophysiology as modulators of other
contractile agents (eg noradrenalin),46–48 cellular
proliferation and/or phenotypic expression.49 This
pathophysiologic state, with an abundance of potent
vasoconstrictors in the setting of impaired vasodilatory mechanisms, prohibits the vascular events
necessary to achieve and maintain an adequate
erection.
Vascular smooth muscle abnormalities
In addition to impaired endothelium-dependent
vasodilation, HF patients also appear to have
dysfunctional endothelium-independent vasodilatation.33,50 Some evidence suggests that over time
arterial compliance decreases.51,52 Abnormal smooth
muscle function may result from altered responsiveness or impaired diffusion of NO through the arterial
wall. Impaired smooth muscle responsiveness is
thought to result, in part, from alterations in
intracellular cGMP function.53 When combined with
endothelium-dependent mechanisms, these pathophysiologic variations may further confound ED.
Drug therapy in heart failure and ED
While treating heart failure may attenuate some of
these physiologic adaptations, several of commonly
prescribed medications may actually cause or
worsen ED. In general, published data on the
prevalence of ED with the use of various medications is limited by the number or sample size of
studies. Logistically, it can also be difficult to excise
medication effects from the consequences of underlying diseases such as heart failure, hypertension
and atherosclerosis. To date, there have been no
studies establishing whether or not the collective
International Journal of Impotence Research
medical treatment of heart failure has beneficial,
deleterious or any net effect on sexual function.
Digoxin
In a community-based epidemiological study of
1709 men, analysis of data on multiple antihypertensive, vasodilator and cardiac medications
revealed that digoxin use had the highest association with complete ED.54 The mechanism underlying digoxin-associated changes in sexual function
remains poorly understood. Early studies by Stoffer
et al55 and Neri et al56 attributed sexual dysfunction
to hormonal alterations observed with digoxin use;
these changes include higher serum estrogen
coupled with lower testosterone and luteinizing
hormone levels. More recent studies of healthy male
volunteers and cardiac patients have failed to
confirm a relationship between digoxin use and
changes in serum hormone levels.57–59 Some studies
on human corpus cavernosum tissue indicate that
sodium-pump activity also has a role in the regulation of erectile function, with pump inhibition
causing contraction and diminution of NO-induced
relaxation.60 Gupta et al54 studied the effect of
digoxin on sodium-pump activity in human corporeal smooth muscle strips in vitro. They concluded
that digoxin-associated alteration of human sexual
function may be due to corporeal smooth muscle
pump inhibition, which promotes contraction and
impedes NO-induced relaxation.
Beta-adrenergic receptor blockers
Beta-blockers are believed to have negative effects
on erectile function.61 Some theories point to
adverse effects of decreased perfusion pressure or
a direct (but unknown) effect on smooth muscle.
Support for the latter mechanism is derived from
the observation that despite pressure-lowering
effects, treatment with alpha-adrenergic receptor
blockers is not associated with ED, and that this
class of medications may actually improve preexisting sexual dysfunction.62 Beta-adrenergic
blocking agents may cause ED by potentiating
alpha-1 adreno-receptor-mediated contraction of
corporal smooth muscle in the penis.1 However, it
is surprising and unclear why not all or even the
majority of treated patients experience such (side)
effects. A prospective, randomized, double-blind
study showed that patients’ sex lives were unaffected by metoprolol treatment.63 In another study,
Wassertheil et al6 demonstrated that the betaadrenergic blocker atenolol did not affect sexual
function. In a study of 96 men with newly diagnosed
cardiovascular disease and without ED, 31%
Why do patients with heart failure suffer from ED?
S Rastogi et al
reported ED after beginning treatment with atenolol
and being informed of its possible adverse sexual
side effects. In contrast, only 3% of men who were
similarly treated reported ED when they were
blinded to the study drug, suggesting that ED with
beta-blockers is related to patient knowledge of
these potential side effects.64 To the contrary, Croog
et al found propranolol use to be associated with
significant sexual dysfunction. More recently, carvedilol has become a preferred agent for beta-blocker
therapy in HF patients. A recent study comparing
carvedilol with the angiotensin-receptor blocker
valsartan demonstrated a decline in sexual activity
within the carvedilol-treated group. Notably, these
patients were hypertensive treated with high doses
of carvedilol, and patients with comorbidities such
as diabetes mellitus and coronary atherosclerosis
were excluded. Additionally, it is unknown if these
data represent deleterious effects of carvedilol or
beneficial effects of valsartan.65 The discrepancy of
the effects of various beta-blockers and dosages may
be related to a differential action on peripheral
structures and or the central nervous system.66 In
summary, the effects of beta-blockade on sexual
function in the HF population have not been clearly
defined. Overall most beta-blockers appear to be
associated with worsening of ED. It is not quite clear
whether beta-blockers do cause ED per se. Further
investigation is needed to clarify the role of betablockers on erectile function in different and larger
populations.
Diuretics
While sexual disorders caused by diuretics have
been reported, the mechanism remains ill-defined.61
In all, 10–20% of patients taking thiazide diuretics
may experience a decline in sexual function.67
Wassertheil et al6 demonstrated that the thiazide
chlorthalidone causes sexual dysfunction. Similar
findings were seen with the use of hydrochlorothiazide as monotherapy for hypertension in a small
study of 12 patients.68 In another study among 177
patients treated with either methyldopa or propranolol for hypertension, total sexual symptom distress score worsened with the addition of
hydrochlorothiazide, with significant worsening in
the group taking propranolol. Among patients taking
captopril, no change in baseline scores appeared for
any sexual symptoms with the addition of hydrochlorothiazide.69 The aldosterone antagonist spironolactone is considered standard therapy for HF
patients and can also cause erectile failure, gynecomastia and decreased libido secondary to its antiandrogen effects.1 These side effects have not been
reported and yet not studied with the use of
eplerenone, which is a newer, more selective
mineralocorticoid receptor antagonist.70
ACE inhibitors and angiotensin receptor blockers
S29
The impact of ACE inhibitors and ARBs on ED is
unclear. Croog et al71 found that the ACE inhibitor
captopril actually enhances sexual function. These
findings are supported by DiBianco’s72 reports that
40–80% of patients treated with ACE inhibitors
experienced improved functional status and sexual
function. It has been suggested that potential
favorable sexual effects of captopril were secondary
to improved cardiac function; however, sufficient
data to support this hypothesis do not exist. There is
even less information available regarding the effects
of ARBs on sexual function. One Japanese study
reported that in hypertensive patients switched
from calcium channel blockers to candesartan, those
patients less than 65 y of age experienced improved
sexual function.73 Another study comparing the
sexual side effects of the ARB valsartan with the
beta-blocker carvedilol demonstrated that following
an initial statistically insignificant decline in sexual
frequency, continuous therapy with valsartan was
associated with recovery or improvement of sexual
activity.74 This favorable sexual profile of valsartan
was confirmed by Dusing,75 who reported a reduction in ED with improved orgasmic function,
intercourse and overall sexual satisfaction in hypertensive patients treated for 6 months. A more precise
definition of the role these agents play in the sexual
functioning in patient with chronic HF remains to
be elucidated.
Electrical therapy/cardiac resynchronization
for heart failure
The placement of a biventricular pacemaker for
chronic resynchronization therapy has become
increasingly common for HF treatment. In general,
there is a paucity of data evaluating the effects of
cardiac pacemakers on sexual or erectile function.
One small study reported that while treating
arrhythmias with pacemaker implantation improved
quality of life in general, but it did not improve
sexual function.76 Currently, there is no data
evaluating the sexual effects of HF patients treated
with resynchronization therapy.
Sexual function in cardiac patients
The effects of a significant cardiac condition on the
vitality of a patient’s sex life have not been
elaborately explored. There are, however, some
small studies demonstrating a general deterioration
in this aspect of a patient’s life after experiencing
a cardiac event.
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S30
Sexual function in patients with heart failure
Jaarsma and colleagues studied 62 heart failure
patients via questionnaire to determine alterations
in a patient’s emotional, social and sexual function.
Most patients experienced a decreased libido, less
frequency of coitus, negative changes in sexual
performance and a general dissatisfaction related
to their sexual function. In this report, however,
these changes did not affect the relationship with
the patient’s spouses.3 In a cohort of 4300 heart
failure patients, 490% reported reduced libido and
erectile problems, which was independent of the
NYHA functional class (unpublished).
Sexual function post myocardial infarction
After myocardial infarction (MI), only two-thirds of
male patients returned to satisfying sexual relations
within 6 weeks, with 90% achieving at least pre-MI
levels of sexual function by 1 y. Importantly, most
patients also experience a decrease in frequency of
sexual relations.77–79 Female patients at 18 months
post-MI reported slightly lower rates of return to
a ‘normal’ sexual function, with 73% having
attempted to resume sexual relations with their
husbands.80 Another comparison between men and
women which was performed to determine whether
there are gender differences in the quantity and
quality of sexual activity showed that a first MI
appears to reduce the frequency of and satisfaction
with sexual activity of women and men equally.81
Sexual function postcoronary artery bypass surgery
In a prospective evaluation of patients postcoronary
artery bypass surgery, Langeluddecke et al82 found
a significant (though modest) improvement in
patient’s marital relationships, level of sexual interest and level of sexual activity compared with the
presurgical status. These findings were consistent
with previous studies.83 In another study by
Papadopoulos et al,84 134 patients were interviewed
about the impact of surgery on their sexuality; 39%
of patients reported decreased frequency of sexual
activity, with 17% of patients and 35% of their
partners expressing fear of resuming sexual activity.
Sexual function postheart transplantation
Mulling et al85 conducted a survey in a cohort of 71
heart transplant recipient patients to assess the
sexual interest, ability and activity before and after
International Journal of Impotence Research
cardiac transplant. The authors found that libido
remained unchanged before and after cardiac transplant. In contrast, erectile rigidity and orgasmic
ability were impaired before and surprisingly declined further after transplantation. Intercourse
frequency was relatively infrequent post-transplant
and was related to problems with erectile rigidity.
However, it needs to be emphasized that these data
were published in 1991, that is, prior to modern
heart failure therapy and prior to the development of
PDE-5 inhibitors.
Treatment of ED in heart failure patients
Optimize heart failure therapy
First priority for patients with HF and ED should
be to optimize heart failure management, according
to the newly updated ACC/AHA guidelines.86
Even though there is no data published whether
optimized heart failure therapy improves ED, it is
assumed that reduced symptoms and improved
exercise capacity contribute to improved sexual
activity.
Secondly, drugs with potential side effects of
sexual dysfunction should be avoided and—if
possible—replaced. Prior to any use of PDE-5
inhibitors or other aphrodisiacs due to our experience, we try to (1) avoid digoxin, (2) avoid thiazide
diuretics, (3) replace beta-blockers, for example,
propranolol with either metoprolol or carvedilol
(due to their alpha-blocking effects) and (4) replace
spironolactone with eplerenone. The above approach should be considered only if clinically
feasible without worsening function or symptoms,
and if affordable by the patients.
Oral phosphodiesterase inhibitors
In March 1998, sildenafil citrate (Viagras) became
the first approved oral drug for ED in the United
States. The role of sildenafil and other PDE-5
inhibitors is to enhance cGMP-NO-mediated vasodilatation with resulting improvement of erectile
function.87–89
Vardenafil (Levitras) and tadalafil (Cialiss) are
newer PDE-5 inhibitors that appear to be as effective
as sildenafil.90–94 All PDE-5 inhibitors are contraindicated with concomitant nitrate or any NO
donator use (nitroprusside, molsidomine, etc).95
Although these newer agents may not have additional cardiac risks compared with sildenafil, there
is less clinical information related to the safety of
these drugs available in patients with heart disease.
Why do patients with heart failure suffer from ED?
S Rastogi et al
The American College of Cardiology and the
American Heart Association in their 1999 consensus
document expressed concerns regarding the lack of
cardiovascular safety data from controlled clinical
trials of sildenafil in men who had ED and
congestive HF. Caution was raised for the potential
interaction of sildenafil with vasodilators commonly
used in congestive HF treatment, potentially resulting in clinically significant hypotension. In this
consensus statement, HF was listed as a relative
contraindication for the use of sildenafil.96 Katz et al
undertook a multicenter, prospective, randomized,
double-blind, placebo-controlled, flexible-dose
study, which addressed concerns raised by the
consensus statement. The results demonstrated that
flexible dosing of sildenafil from 25 to 100 mg was
well tolerated, improved erectile function and
increased satisfaction with sexual performance in
ambulatory subjects who had mild to moderate
congestive HF compared with subjects who received
placebo.97 These findings were in accord with two
previous small investigations of the effects of
sildenafil in patients with HF.98,99 No clinical safety
data on the use of newer phosphodiesterase inhibitors, vardenafil and tadalfil, is available in the heart
failure patient population.
Treatment options other than sildenafil can be
pursued in patients with HF as they would be in the
general population. As far as we know, there are no
specific cardiovascular effects of androgen replacement therapy, intraurethral suppository, penile
injection therapy, penile prosthesis or vacuumassisted erection devices, as well as no long-term
negative therapy effects have been reported in heart
failure patients.
Surgical management
Men who are not candidates for or who fail
treatment with an oral agent may select second-line
therapies such as intraurethral prostaglandins, penile injection therapy, hormone therapy or a vacuum
erection device. Since this might be unpleasant for
some, these patients may be candidates for surgical
intervention such as penile angioplasty, penile
revascularization or implantation of a penile prosthesis.
Percutaneous angioplasty for ED
Percutaneous transluminal angioplasty (PTA) is
common semi-invasive interventional method used
for coronary arteries, peripheral arteries and, more
recently, carotid arteries with a low complication
rate. Little data exist, however, for the treatment of
ED. High-quality diagnostic angiographic studies
and their accurate interpretation are prime requirements for proper patient selection. Venogenic
impotence must be excluded by cavernosometry
and cavernosography.100 Only patients with focal
atherosclerotic lesions in either the hypogastric
(internal iliac), common iliac or even the pudendal
arteries might be potential candidates for PTA. Only
few small studies have reported success rates of
57–84% with resolution of ED after PTA of the
common and external/internal iliac arteries and the
internal pudendal arteries.101–103 Owing to our
limited experience with individual successfully
treated men, we believe that PTA represents a future
potential treatment option for a selected group of
patients; however, randomized controlled studies
are required to establish its definitive role in the
treatment of arteriogenic impotence.
S31
Surgical revascularization
Penile revascularization surgery is a rational and
effective treatment for ED resulting from localized
arterial lesions. Among vascular surgeons performing surgical revascularization, the accepted criteria
for arteriogenic ED include: ageo50 or 55 y, a
negative response to intracavernosal injection tests,
fewer than one or two cardiovascular risk factors, no
history of diabetes mellitus and normal corporal
veno-occlusive function,104,105 which—unfortunately—represents the minority of affected patients.
It is assumed that increased intracavernosal pressure is achieved by revascularization surgery, but
studies to demonstrate this are lacking. Different
approaches have been reported such as anastomizing the inferior epigastric artery to the corpus
cavernosum (Michal et al106); to the dorsal penile
artery (Michael 2107); to the deep dorsal vein (Virag
et al108); and an anastamosis between the inferior
epigastric artery and the deep dorsal vein and artery
of the penis (Hauri109). A recent study by Kawanishi
et al111 found penile revascularization surgery
treatment suitable only for young men with no
significant difference in the subjective outcome
between the so-called Furlow–Fisher modification
of the Virag V (FFV5; Furlow et al110) procedure and
the Hauri procedure. Currently, revascularization
surgery for ED represents a therapeutical alternative
for a limited group of patients, with a vascular
anatomy and morphology suitable for graft anastomoses, who failed all other noninvasive options as
well as for a limited group of vascular surgeons.
Treatment of depression
Psychological counseling may help alleviate symptoms of depression and thereby help restore sexual
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function. While antidepressant drugs can be used,
it should be noted that many of the newer and more
effective antidepressants, in particular selective
serotonin reuptake inhibitors (SSRI, such as fluoxetine, sertraline and paroxetine) can decrease libido
and worsen erectile function.112 Trazodone, clomipramine and other tricyclic antidepressants,
however, can cause delayed or retarded ejaculation
(a side effect that actually may be beneficial for some
men who are suffering from premature ejaculation).24,113 It is unclear, however, whether wellcontrolled, treated depression does improve sexual
function in patients with ED while the drug’s side
effects might worsen sexual function, resulting in a
zero net balance. An ethically reasonable approach
to this dilemma is to adequately treat depression
and to counteract SSRIs side effects by use of PDE-5
inhibitors.
anxiety, couples need to receive information about
the physiological requirements of sexual activity,
the pathophysiology of heart failure (including its
treatment) relative to sexual function and the
psychological sequelae of heart failure. Westlake
et al117 also found a disparity between the individuals’ and their sexual partners’ perception of the
changes in their sexual relationship, reinforcing that
instructions and counseling should be directed at
both parties. This finding has been observed in
previous studies as well.118–122 Advanced heart
failure does not necessarily mean the end of
satisfying sexual relations, but it is important that
health-care professionals address the changes related to the disease, clarify misconceptions and
provide appropriate counseling, in particular in
patients with chronic heart failure.
Future options
Hemodynamic stress reduction
It is possible to reduce physiologic demands of
sexual activity, which is recommended in patients
with heart failure. It has been assumed that man
would perform less physical work during sexual
intercourse in supine (as opposed to the manon-top) position. However, there appears to be very
little114 or no significant difference115 in hemodynamic parameters between the two positions,
even though this may vary individually. It has also
been suggested that patients should avoid eating
large meals or alcohol use just before sexual
intercourse and avoid extremes of temperature.116
Patients may be advised to engage in sexual activity
when they feel well rested (in the morning rather
than at the end of the day), and, interestingly, it has
been proposed that the use of waterbeds may also
reduce the number of metabolic equivalents required for sexual activity.3 However, most of these
recommendations are intuitive and not based on
controlled scientific data.
Sexual counseling
Investigators have documented that many cardiac
patients are uncomfortable discussing issues concerning sexual activity or function.78 Many patients
may become noncompliant with their heart failure
medical regimen since they read the packet inserts’
side-effect profile on sexual function and strongly
believe it causes or aggravates their sexual problems.
Patients and spouses have informational needs
about their sexual problems, specifically with regard
to a change in frequency, interest and ability to have
sex; most patients are also interested in having their
concerns addressed.117 To dispel their fears and
International Journal of Impotence Research
Further clinical studies with selective antagonists
of ET receptors might be considered given their
established elevation in HF and causative role in ED.
The Rho A/Rho kinase pathway is emerging as a
novel player in the regulation of penile erection, and
future investigations may further define its role
in ED and HF.123 Neovascularization is an emerging
approach to the reversal of impaired cavernosal
artery flow. Intracavernosal injection of vascular
growth factors has been demonstrated to be feasible
in animal models.124 Also, gene therapy may be a
treatment of the future. Studies are currently being
conducted in animals with gene transfer of endothelial nitric oxide synthase to the penis of aged
rats for the potential application of gene therapy
for the treatment of ED.125
Conclusion
ED is highly prevalent among patients with HF, and
can significantly and adversely affect quality of life.
Causes of ED in HF patients are multifactorial, and
may be due to direct vascular etiologies, reduced
cardiac capacity, neurohormonal changes or treatment regimens specific to HF. Despite the unique
issues of sexual dysfunction in the setting of HF,
most patients are not receiving adequate counseling
in this matter. Addressing the sexual concerns of
these patients is important, as it may improve
medical compliance as well as quality of life.
Currently available effective oral medical treatment
options are limited to the PDE-5 inhibitor sildenafil,
which targets the NO/cGMP pathway. Sufficient
safety data on the newer PDE-5 inhibitors in HF
patients is lacking. Sexual function and potential
dysfunction requires increased awareness among
Why do patients with heart failure suffer from ED?
S Rastogi et al
cardiologists, adequate assessment and appropriate
counseling. Interestingly, in our experience, most
patients with ED and chronic stable heart failure can
be successfully treated for their erectile problems.
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