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European Heart Journal (2000) 21, 255–258
Article No. euhj.1999.1926, available online at http://www.idealibrary.com on
Hotline Editorial
Mitral valve prolapse: The Merchant of Venice or
Much Ado About Nothing?
Mitral valve prolapse has entered its age of maturity,
with a lifetime that spans almost four decades since
Barlow et al.[1] first demonstrated the association of
mid-systolic clicks and late systolic murmurs with
systolic aneurysmal billowing of the posterior mitral
leaflet into the left atrium. In the intervening years,
mitral valve prolapse has been associated with a wide
spectrum of definitions and a variety of terms.
Through this initial haze of terminology, it has now
been clarified that mitral valve prolapse is not a single
entity but a spectrum of abnormalities with a variety
of clinical, echocardiographic and pathological features. Morphologically, the extremes of this spectrum
are normal-appearing mitral leaflets that billow
mildly into the left atrium and redundant leaflets
resulting from marked myxomatous proliferation of
the spongiosa component of the valve and elongation
of the cordal apparatus. Mild leaflet displacement
may not be accompanied by mitral regurgitation
whereas marked billowing with loss of systolic
apposition can result in grave regurgitation.
Mitral valve prolapse has a strong hereditary
component and is most frequently a primary condition[2–5]. However, it is often associated with many
disorders and the readily emerging question is, as
Malcom expressed it[2], to what extent are these
associations a casual coincidence, a common link, or
an expression of a fundamental genetic disturbance.
Commonly associated conditions are heritable
disorders of connective tissue, such as the Marfan
syndrome, the Ehlers–Danlos syndrome, osteogenesis
imperfecta, adult polycystic kidney disease and pseudoxanthoma elasticum. Mitral valve prolapse is also
associated with congenital abnormalities of the thorax such as pectus excavatum, shallow chest and
straight back. The disorder can also coexist with
rheumatic mitral stenosis and in hypertrophic cardiomyopathy prolapse of the posterior leaflet may
accompany the anterior displacement of the anterior
leaflet. In ischaemic heart disease, apart from chance
association, mitral valve prolapse may be the result of
papillary muscle dysfunction, or the cause which
leads to ischaemia through increased tension on the
base of the involved muscle.
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As regards clinical presentation, the majority
of patients are asymptomatic[3–6]. Symptoms may
be related directly to mitral valve dysfunction.
Boudoulas et al. have described the mitral valve
prolapse syndrome, in reference to a subset of
patients whose cardiac and non-cardiac symptoms
cannot be explained by mitral valve abnormalities
and dysfunction alone. Such patients present with
a characteristic non-ejection click and a variety of
non-specific symptoms, such as fatigue, palpitations,
chest pain, postural orthostasis, syncope or presyncope, and neuropsychiatric symptoms. These
symptoms may result from neuroendocrine or autonomic dysfunction[3–7], and impairment of left atrial
function might have a contributory role[3,7–8]. In
addition, patients may present with a variety
of symptoms originating from both valvular and
autonomic dysfunction.
The most important aspect of a disease is its clinical
importance and this can be determined following
three steps that should be taken carefully and are
largely interrelated. First, the true prevalence of the
disease should be defined. Second, the true risk
associations should be determined with flawless methodology. Finally, diagnostic criteria should categorize
the patients according to the severity of the risk.
Unfortunately, uncertainty regarding the true prevalence of mitral valve prolapse on the one hand and
the serious complications that have been ascribed to
the abnormality on the other, constitute the doublefaceted confusion with which the medical community
has been confronted. This confusion has often led to
undue labelling and ‘overtreatment’ of mostly young
‘patients’, with important psychological consequences
and socioeconomic implications.
Starting with a ‘flexible’ definition such as that of
‘mitral valve prolapse’, it is apparent that there are
inherent difficulties in pursuing the determination
of its true prevalence. In this environment, the crucial
role of diagnostic techniques is to minimize
false-positive results. This can be achieved through
evolution and refinement of diagnostic techniques
and increasing knowledge regarding disease mechanisms. Diagnostic tools used in the diagnosis of the
2000 The European Society of Cardiology
256
Hotline Editorial
abnormality have included auscultation, M-mode,
two dimensional and transoesophageal echocardiography, left ventriculography and direct histopathological inspection of the mitral valve apparatus.
Based on these diagnostic techniques, many criteria
both major and minor have been proposed and some
non-specific findings have been associated with the
entity[9].
Although these criteria may help orient the clinician towards the disorder, they do not clear up the
confusion as to what is its real prevalence. The
prevalence has been reported to range from 5 to 10%
in the general population and even higher among
young women[10–11]. Echocardiography has been an
invaluable diagnostic tool, but at the same time has
undoubtedly catalyzed over-diagnosis. Given that the
generic definition of prolapse is displacement of the
mitral valve leaflets relative to their surrounding
tissues, M-mode echocardiography has an obvious
disadvantage: it does not display the leaflets in relation to their surrounding annular attachments. Moreover, images obtained are strongly dependent on
the orientation of the transducer. Two-dimensional
echocardiographic views overcome such limitations,
but nevertheless, the non-planar ‘saddle shape’ of
normal mitral leaflets that has been documented in
three-dimensional studies[12] can give the impression
of prolapsing leaflets in certain echocardiographic
views. Finally, an additional factor that has
contributed to the reportedly high prevalence is selection bias, an inherent limitation of the numerous
referral-based studies.
Volunteers responding to an advertisement or
agreeing to participate after random selection, do not
represent a typical community sample since they are
more health-concerned, either due to history of a
heart murmur or positive family history. In a recent
study, Freed and colleagues[13] used rigorous echocardiographic criteria for the diagnosis of mitral valve
prolapse in an unselected, community-based sample
of ambulatory patients. Based on these diagnostic
criteria and on such a population selection, prevalence was lower than previously reported. Classic
mitral valve prolapse was defined as superior displacement of the mitral leaflets, by more than 2 mm
during systole, with maximal leaflet thickness of at
least 5 mm during diastasis; non-classic prolapse was
defined as displacement by more than 2 mm, with a
maximal thickness of less than 5 mm. Using these
criteria in 3491 screened subjects, 2·4% had mitral
valve prolapse, with 1·3% fulfilling the criteria
according to the classic definition and 1·1% according
to the non-classic definition.
Although mitral valve prolapse is generally considered a benign condition, serious complications
Eur Heart J, Vol. 21, issue 4, February 2000
have been ascribed to it, including infective endocarditis, severe mitral regurgitation needing surgical
intervention, heart failure, cerebral and coronary
embolic events, arrhythmias and even sudden
death[14,15]. However, it appears that the actual risk,
although not negligible in specific subgroups, is less
compared to that of early reports. Explanations for
this discrepancy can be sought either in the referral
bias or in the considerable number of retrospective
identifications of mitral valve prolapse among
patients with complications in some of these early
studies. Zuppiroli et al.[6] in an 8 year plus follow-up
study reported a low (1% per year) overall rate of
fatal and non-fatal complications. Progressive mitral
regurgitation is the most frequent complication and
the risk is greater in patients with both murmurs
and clicks than in those with an isolated click.
The incidence of infective endocarditis also rises in
the presence of a murmur, whereas patients with only
a mid-systolic click are at very low risk[16]. It appears
that the risk of sudden death increases slightly in
patients with severe valvular deformities or severe
mitral regurgitation[4,17,18]. The association between
stroke and mitral valve prolapse has been controversial. In a recent study, Gilon et al.[19], using highly
specific echocardiographic criteria for mitral valve
prolapse could not demonstrate an association in
young people, although a small association cannot be
ruled out. Valve redundancy appears to be a significant factor predisposing to adverse effects[17,20].
According to Zuppiroli et al.[6] the risk for complications is higher in men, in subjects aged over 45
years, and in those with evidence of significant mitral
regurgitation (holosystolic murmur and left-sided
chamber enlargement).
In light of the new data that have emerged during
recent years, management of mitral valve prolapse
can be approached more rationally (Fig. 1).
Nishimura and McGoon[21] have suggested that the
hallmarks of this approach should be the echocardiographic categorization of patients according to
rigorous criteria that should be adopted by all
laboratories. Indeed, patients with mild bulging of
morphologically normal-appearing leaflets have a
minor, or no, risk of complications. In the absence
of a systolic murmur, reassurance and follow-up
at moderate intervals with clinical evaluation and
echocardiography is adequate[4]. Antibiotic prophylaxis against infective endocarditis is optional and
may be unnecessary. In the presence of a systolic
murmur, antibiotic prophylaxis is justified and
follow-up should be frequent (e.g. every 2 years).
Patients with redundant and thickened leaflets
are considered as having a primary form of the disease and the mainstay of treatment is close patient
Hotline Editorial
257
Mitral valve prolapse-treatment
2-D echocardiography using
standardized, rigorous criteria
risk
Normal variant form
Primary form
Systolic murmur
–
+
• Reassurance
• Antibiotic prophylaxis
• Antibiotic prophylaxis
• Follow-up more frequent (2 years)
optional
• Follow-up moderate (5 years)
Figure 1
• Antibiotic prophylaxis
• Follow-up close
every year or earlier if
substantial MR
• Optimization of afterload
• Consider early valve repair for
significant MR
A logical approach in the management of mitral valve prolapse.
observation. Clinical evaluation and echocardiographic follow-up should be performed every year or
earlier if substantial mitral regurgitation is present.
Prophylaxis against infective endocarditis is mandatory. In the presence of mitral regurgitation, afterload
should be optimized and development of resultant
left ventricular failure should be treated, as in other
patients, with severe mitral regurgitation. Reconstructive surgery without valve replacement is
increasingly performed with very good immediate
results (approximately 2% operative mortality) and
favourable long-term outcome[22].
These favourable results are an incentive for early
surgery before ventricular dysfunction occurs. Betaadrenoreceptors are useful in the management of
palpitations or associated myocardial ischaemia.
Severe arrhythmias may need further electrophysiological investigation. Finally, it should be emphasized
that despite the risk of complications in specific
patient subgroups, the majority of patients remain
asymptomatic throughout their lives. Follow-up
assessment and reassurance are all that is needed for
such patients, who do not deserve being labelled for
their entire lives as having a potentially malignant
disease.
Does the mitral valve prolapse syndrome mercilessly claim the life of its patients, like Shylock, in the
Merchant of Venice, who claimed the heart of Portia’s
lover? Or has too much fuss been made and too many
literature pages been wasted on something almost
non-existent? The truth, as with most things in real
life, lies somewhere in the middle. Prudence in diagnosis, based on rigorous criteria and robust epidemiological data, will define the true prevalence of the
disease and outline the risks. Modern technology and
maturity is on our side.
C. STEFANADIS
P. TOUTOUZAS
Department of Cardiology,
Hippokration Hospital,
Athens Medical School,
Athens, Greece
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