Expert Review of Cardiovascular Therapy

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Mitral stenosis in 2019: changing approaches for

changing times

Guy Lloyd, Sveeta Badiani, Marta Costa, Karen Armado & Sanjeev
Bhattacharyya

To cite this article: Guy Lloyd, Sveeta Badiani, Marta Costa, Karen Armado & Sanjeev
Bhattacharyya (2019) Mitral stenosis in 2019: changing approaches for changing times, Expert
Review of Cardiovascular Therapy, 17:7, 473-477, DOI: 10.1080/14779072.2019.1632190

To link to this article: https://doi.org/10.1080/14779072.2019.1632190

Published online: 21 Jun 2019.

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EXPERT REVIEW OF CARDIOVASCULAR THERAPY
2019, VOL. 17, NO. 7, 473–477
https://doi.org/10.1080/14779072.2019.1632190

EDITORIAL

Mitral stenosis in 2019: changing approaches for changing times

Guy Lloyda,b,c,d, Sveeta Badiania,b, Marta Costaa,b, Karen Armadoa,b and Sanjeev Bhattacharyyaa,b,c,d
a
Echocardiography Laboratory, Barts Heart Centre, St Bartholomew’s Hospital, London, UK; bHeart Valve Clinic, Barts Heart Centre, St
Bartholomew’s Hospital, London, UK; cWilliam Harvey Research Institute, Queen Mary & Westfield, University of London, London, UK; dInstitute of
Cardiovascular Sciences, UCL, London, UK

ARTICLE HISTORY Received 22 April 2019; Accepted 12 June 2019

KEYWORDS Mitral stenosis; heart valve; echocardiography; guidelines; structural intervention; mitral valve replacement

The clinician’s concept of mitral stenosis (MS) is often based a female preponderance for both degenerative and rheumatic
around the model of rheumatic disease in younger patients. In MS [3,7–9]. Why women are more likely to develop stenosis is
such rheumatic patients, management is generally clear and not known.
current guidelines [1] offer a structured approach to investiga- Current European Society of Cardiology/European
tion and treatment. However, as in many other cardiovascular Association of Cardiothoracic Surgery (ESC/EACTS) [1] suggest
diseases, the patient profile in countries with advanced econo- balloon valvotomy or surgery for patients with symptomatic
mies has changed. Patients with MS today are older and suffer moderate or severe MS defined as a mitral valve area (MVA) of
from multiple diseases that effect cardiac function. With less than 1.5cm2. In those with significant MS and no symp-
advancing age the pathology also becomes more complex, toms, intervention may be offered in line with a very narrow
and there is an increasing shift from rheumatic to degenera- set of indications to prevent thromboembolism or pulmonary
tive MS caused by mitral annular calcification (MAC) encroach- hypertension. Although the guidelines also allude to interven-
ing on valve leaflet function [2]. Conventional imaging tion with those with mitral valve areas greater than 1.5cm2 no
approaches (usually by echocardiography) have involved real guidance about how to assess this situation is provided.
understanding obstruction at the level of the valve. The mitral A major weakness in the guidance is that it does not specifi-
valve area reduces which impedes flow resulting in an atrio- cally differentiate between rheumatic and degenerative mitral
ventricular pressure gradient, raised LA pressure and ulti- stenosis, despite the latter having a different pathology, dif-
mately pulmonary hypertension. This is an oversimplification ferent patient profile and very different outcomes to
which becomes more clinically relevant as the disease process intervention.
and the clinical profile of the patients become more compli- A frequent clinical scenario is a breathless patient with
cated. All of these factors mean our current approaches to MSan MVA > 1.5 cm2 who has either no other apparent
medical, surgical and percutaneous management may not cause in the case of rheumatic disease, or multiple possible
deliver equivalent outcomes compared with more conven- causes in the case of degenerative disease. Pregnancy can act
tional rheumatic patients. as a biological model because cardiac output involuntarily
MS remains a relatively rare disease which in a recent large rises to meet increased metabolic demand. Cardiac events
analysis of public health records in Sweden was found in only and mortality are frequent in women with a mitral valve orifice
1917 (0.02%) individuals [3]. For comparison overall, the rates greater than 1.5 cm2. Up to 20% of women with mild MS
for valvular heart disease in this study were 0.65% across all develop pulmonary edema [10]. MS therefore must still be
age groups with a dramatic increase from the fifth decade considered the likely cause of breathlessness in patients with
onwards. In a recent UK cohorts the MS was found in 0.1% in mild disease and no other reason for symptoms. Augmenting
healthy screened subjects over 65 years [4], while in the US, flow across the mitral valve assessed either by exercise or by
a prevalence of 0.2% in those over 75 undergoing population dobutamine infusion may reveal important hemodynamic
screening has been noted [5]. Surprisingly, mitral stenosis findings. The valve resistance, a measure which incorporates
seems to be following the same age trajectory as other valve both gradients and flow, is an important predictor of pulmon-
diseases, and, although patients with prior rheumatic fever are ary vascular changes [11] and although not used in routine
still 3.5 times more likely to suffer from MS, many cases have practice may better describe the obstructive character of the
no antecedent rheumatic history nor clear rheumatic changes valve than gradient or valve area alone.
on echocardiography. In the EuroHeart survey (limited to Bicycle or dobutamine stress echocardiography can be par-
moderate and severe disease) which is now more than 15 ticularly clinically useful in this situation, giving the opportu-
years old, the proportion of cases with degenerative disease nity to augment flow and measure the resultant change in
was 12.5% [6]. This trend suggests a shift from rheumatic to hemodynamics non-invasively. The test allows an objective
degenerative valvular pathology with advancing age. There is measure of exercise performance, it also permits a measure

CONTACT Guy Lloyd guy.lloyd@bartshealth.nhs.uk Heart Valve Clinic & Echocardiography Laboratory, Barts Heart Centre, St Bartholomew’s Hospital,
London, UK
© 2019 Informa UK Limited, trading as Taylor & Francis Group
474 G. LLOYD ET AL.

Figure 1. Increasing transmitral gradients (a-c) and tricuspid peak velocity (related directly to PA systolic pressure) (B & D) during exercise stress echocardiography.

of the heart rate response to exercise (excessive tachycardia

causes a disproportionate increase in gradient) as well as
allowing a comprehensive assessment of change in transmitral
gradient, mitral valve area and the pulmonary artery systolic
pressure (Figure 1) [12]. Grimiladi et al. undertook stress echo
in patients with MS and a valve area of 1.0–1.5 cm (above the
indication for surgery at the time of study design) and found
that 75% had either symptoms or high gradients with or
without important elevations in PA systolic pressure [13].
Fifty percent had an exercise tolerance less than 50 W, and
most importantly, all those with symptoms underwent inter-
vention with a response rate of more than 80% (defined as
NYHA 1 at 6 months). Laufer-Perl demonstrated that a range
of complex cardiac parameters (stroke volume reserve and
chronotropic incompetence) as well as abnormalities of lung
function predicted effort intolerance in a group of patients
with mild MS, effort intolerance being observed in all cases
when compared to control [14].
Obstruction at the level of valve is a key evaluation para-
meter, but how the left atrium and the left ventricle deal with
the pressure is also an important determinant of pulmonary
hypertension and symptoms. Understanding the physical prop-
erties of both the atrium and the ventricle is especially impor-
tant when symptoms and valve area are discordant. At its most
extreme the atrial wall can be almost completely replaced by
fibrosis [15,16] thus unable to accommodate the higher pres-
sures generated when heart rate and flow rates increase. The
total net compliance of the atrium and ventricle provides
a more comprehensive assessment of the hemodynamic con-
sequences of MS and can be non-invasively estimated from
transmitral Doppler echocardiography using a directly mea-
sured MVA and the downslope of the transmitral Doppler
Figure 2. (a) 2 and 3D transoesophageal echocardiography demonstrating
trace [17,18]; it can also be measured invasively during valvu- extensive severe annular and leaflet calcification resulting in degenerative MS.
loplasty procedures. A low combined net compliance of ven- (b) Circumferential annular calcification demonstrated by multislice compu-
tricle and atrium appears to track well to disproportionate terised tomography.
 EXPERT REVIEW OF CARDIOVASCULAR THERAPY 475

pulmonary hypertension, symptoms, response to treatment abnormal profile of trans mitral flow may be the cause of
and morbid cardiac events [17]. Compliance is however not some of ventricular dysfunction [22] and hence be reversible.
a fixed phenomenon; some, but not all, patients see This remains an area of uncertainty.
a significant increase in compliance atrial after valvoplasty sug- Low flow aortic stenosis is a well recognized clinical entity
gesting the pressure/function relationship is to some extent and much has been written about how best to investigate and
load dependent. Those who cannot modulate compliance manage the condition [1]. It is increasingly recognized that
after treatment get the worst symptomatic response to improv- gradients across the mitral valve also fall as transmitral flow
ing the balloon valvotomy [19]. reduces leading to an analogous syndrome of low flow low
Classically MS is considered a disease in which the ventricle gradient mitral stenosis [23]. This is conventionally defined as
is spared the effects of excessive loading conditions. Recent a mean MVA of less than 1.5 cm2, measured directly from
evidence from deformation imaging echocardiography [20,21] planimetry of the echocardiogram, and mean gradient of less
has demonstrated significant ventricular dysfunction although than 10 mmHg and a transmittal flow less than 35 mls/m2,
with a preserved ejection fraction, the pattern of dysfunction estimated from transmitral doppler. As with low flow aortic
favoring the basal and mid segments. This has prompted the stenosis, it is often ambiguous if the valve or other factors in
hypothesis that the rheumatic pancarditis may also result in the circulation are limiting flow and valve opening. Recent
long-term ventricular fibrosis which may limit the benefits of evidence has suggested that these patients are very different
treatments to the mitral valve. Sengupata et al. recently noted being older, more ill, with more atrial fibrillation and more
that ventricular abnormalities resolve after relief of mitral subvalvular disease. After valvotomy, they have a lower reduc-
stenosis, suggesting that ventricular loading due to the very tion in LA pressure, and most importantly a worse symptomatic

Figure 3. Proposed algorithm for the evaluation and treatment of patients presenting with symptomatic mitral stenosis in circumstances not covered by ESC/EACTS
guideline [1].
476 G. LLOYD ET AL.

response. Measured directly in this study, the main limitation of degenerative mitral stenosis and the increasingly recognized
flow was at the level of the vasculature with significantly ele- syndrome of low gradient severe mitral stenosis. In these
vated after-load, rather than intrinsic contractile abnormalities groups, the outcomes of intervention are uncertain at best
of the left ventricle. Similar disappointing results in this group and hazardous at worst, so very meticulous evaluation of each
have been observed with mitral valve surgery [23]. aspect of the anatomy and physiology is indicated to make
Degenerative MS because of mitral annular calcification is best interest clinical decisions. Stress echocardiography plays
an increasingly common diagnosis (Figure 2). In the original a pivotal role in establishing changes in trans valvular gradient
EuroHeart survey, 12% of mitral stenosis was degenerative and and pulmonary artery systolic pressure, thus refining the
is likely to have risen in the intervening decade [6]. It is opportunities for therapy. Current guidelines help little with
a complex disease to evaluate for most of the reasons outlined the management of these patients so careful multidisciplinary
above. It tends to be a disease of the elderly, who suffer from evaluation is required to achieve the best clinical outcomes.
more comorbidities, reduced atrial and ventricular compliance
as well as abnormal vascular function. Diastolic LV dysfunction
Funding
is common and sometimes challenging to differentiate clini-
cally. Detailed morphological evaluation of the valve, with TOE This paper was not funded.
if necessary, is required. Balloon valvoplasty has no role in this
disease as the pathology does not involve commissural fusion
and surgery comes at a significant risk of complications Declaration of interest
[24,25]. In recent years the deployment of TAVI valves within G Lloyd holds research awards from Medtronic; grants from the Edwards
the ring of annular calcification has emerged as a less invasive foundation; and honoraria from Edwards Lifesciences in the field of heart
alternative to surgery. The outcomes hemodynamic and symp- valve disease. The authors have no other relevant affiliations or financial
involvement with any organization or entity with a financial interest in or
tomatic results of valve in MAC are good but at the penalty of financial conflict with the subject matter or materials discussed in the
very significant mortality, in the largest series to date this was manuscript apart from those disclosed.
25% at 20 days and 54% at 12 months [26]. This field is
moving very fast with a constant pipeline of new devices
and approaches in development. It seems likely that by the Reviewer disclosures
middle of the next decade percutaneous treatments will be Peer reviewers on this manuscript have no relevant financial or other
the mainstay of treatment. relationships to disclose.
Although the current international consensus guidance
does not satisfactory cover many of the scenarios outlined
above, some common themes emerge. Firstly, the outcomes References
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