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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 1, January/February 2018
AFRICA
51
Review Article
Left ventricular remodelling in chronic primary mitral
regurgitation: implications for medical therapy
Keir McCutcheon, Pravin Manga
Abstract
Surgical repair or replacement of the mitral valve is currently
the only recommended therapy for severe primary mitral
regurgitation. The chronic elevation of wall stress caused by
the resulting volume overload leads to structural remodelling
of the muscular, vascular and extracellular matrix compo-
nents of the myocardium. These changes are initially compen-
satory but in the long term have detrimental effects, which
ultimately result in heart failure. Understanding the changes
that occur in the myocardium due to volume overload at the
molecular and cellular level may lead to medical interven-
tions, which potentially could delay or prevent the adverse
left ventricular remodelling associated with primary mitral
regurgitation. The pathophysiological changes involved in
left ventricular remodelling in response to chronic primary
mitral regurgitation and the evidence for potential medical
therapy, in particular beta-adrenergic blockers, are the focus
of this review.
Keywords:
mitral regurgitation, left ventricular remodelling,
medical therapy, beta-blocker
Submitted 30/5/16, accepted 12/1/17
Cardiovasc J Afr
2018;
29
: 51–65
www.cvja.co.zaDOI: 10.5830/CVJA-2017-009
Mitral regurgitation (MR) is caused by failure of adequate
coaptation of the anterior and posterior mitral leaflets during
left ventricular contraction, resulting in various degrees of
regurgitation of blood from the left ventricle (LV) into the left
atrium (LA). The result of this regurgitation is twofold. Firstly,
there is a reduction in forward stroke volume (FSV) into the
aorta, with subsequent reduction in perfusion. Secondly, there is
an increase in LA blood volume during ventricular systole, which
results in an increase in left ventricular preload, the so-called
‘volume overloaded’ state.
MR is classified as either primary (organic) or secondary
(functional), and acute or chronic.
1
Causes of acute MR include
infective endocarditis and spontaneous cordal rupture and will
not be discussed further in this review. Chronic secondary MR
can be ischaemic and/or non-ischaemic in nature and therapies
for secondary MR range from medical to surgical.
2
By contrast,
chronic primary MR is predominantly caused by degenerative
disease in developed countries,
3
and rheumatic heart disease
(RHD) in developing countries.
4
RHD is one of the major
contributors to the aetiology of heart failure in Africa, where
it remains the most common form of acquired cardiovascular
disease in children and adults.
4
Current therapy for patients with severe chronic primary
MR, as recommended by the European Society of Cardiology
guidelines,
1
comprises surgical repair or replacement in patients
who are surgical candidates, or conservative (i.e. palliative)
therapy in patients with very poor left ventricular function
who are deemed to be poor surgical candidates. At present,
there is no recommendation for drug therapy in patients with
any degree of chronic primary MR. However, once heart
failure develops, angiotensin converting enzyme inhibitors
(ACE inhibitors), beta-blockers and spironolactone may be
considered.
5
Although there have been several recent reviews focusing on
ventricular remodelling in ischaemic heart disease, hypertensive
heart disease and aortic stenosis, there have been few recent
reviews on pathological left ventricular remodelling in patients
with primary MR.
6-8
In this review we focus in particular on the
pathophysiological changes seen in the myocardium of the LV
due to volume overload caused by chronic primary MR. We also
discuss medical interventions that may attenuate or reverse the
adverse changes seen in chronic primary MR, focusing on data
related to the use of beta-blockers in these patients.
Pathophysiological changes in the LV in
chronic primary MR
Primary MR may present acutely, as a slowly progressive disease,
or as chronic progressive MR with sudden deterioration related
to acute changes in mitral valve anatomy such as a ruptured
cord. Acute MR is usually a medical emergency requiring
emergent surgery and is not the focus of this review.
Patients with chronic primary MR are often asymptomatic
for long periods of time before presenting at a late stage in heart
failure. During this period, there is development of progressive
left ventricular dysfunction as the LV is remodelled in an attempt
to produce an adequate forward stroke volume.
9,10
Five- to
Division of Cardiology, Department of Internal Medicine,
Charlotte Maxeke Johannesburg Academic Hospital and
University of the Witwatersrand, Johannesburg, South Africa
Keir McCutcheon, BSc (Hons), MSc, MB BCh, FCP (SA), Cert
Cardiol (SA),
keir_mccutcheon@hotmail.comPravin Manga, MBBCh, FCP (SA), PhD, FRCP (UK)