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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 1, January/February 2018

AFRICA

59

that this drug caused worsening left ventricular dimensions

and function in animal subjects with primary MR. By contrast,

treatment of dogs with the selective beta-blocker atenolol

improved left ventricular remodelling,

90

whereas treatment

with metoprolol in animals and humans have had mixed

results.

108,180,196,197,199,200

Thirdly, an important question is whether patients presenting

in more advanced stages of left ventricular remodelling will

respond to anti-remodelling therapy or whether the wall stresses

determined by the Laplace law will outweigh any potential

beta-blocker effect. In this regard, the findings of Pat

et al

.

200

are interesting because although there were improvements in

cardiomyocyte contractility and beta-receptor responsiveness,

left ventricular remodelling was not attenuated by metoprolol. It

was postulated that

β

-AR blockade failed to preserve interstitial

collagen loss and therefore failed to prevent ongoing myocyte

slippage. There appears to be a strong early adrenergic response

to chronic primary MR,

56

and beta-blocker therapy before onset

of left ventricular dilatation may have more benefit.

Lastly, in patients with rheumatic mitral valve disease, there is

a possibility that rheumatic fever causing rheumatic carditis may

have long-lasting effects on the myocardium, attenuating reverse

remodelling by beta-blockers.

Conclusion

Left ventricular remodelling in response to the volume load

created by chronic primary MR is a complex process that stems

from excessive diastolic stretch of myocytes. Excessive stretch

triggers activation of numerous signal transduction pathways,

resulting in an initial adaptive remodelling process in the form

of eccentric hypertrophy. However, chronic activation of these

pathways results in abnormal increases in ROS, catecholamines,

angiotensin II and inflammatory cytokines. This is followed by

a transition to adverse remodelling involving cardiomyocyte

apoptosis and interstitial collagen loss, common to all forms of

heart failure.

Limited data do not support the routine long-term use of

afterload-reducing agents for the treatment of chronic primary

MR. By contrast, there is pre-clinical data demonstrating that

β

-AR blockade reverses remodelling caused by the volume

overload of chronic primary MR, and there are some recent

clinical data to support this hypothesis. However, some studies

demonstrated worsening left ventricular remodelling with beta-

blocker therapy. Whether these contrasting outcomes are related

to differences in beta-blockers, varying experimental models

or differences in timing of therapy will need clarification.

Ultimately, further studies are required to elucidate the exact

mechanisms involved, and large randomised clinical trials are

needed to clarify the role of these agents for patients with chronic

primary MR.

The authors thank Drs Eric Klug and Thomas Kalk for their valuable

comments, and Dr Lindsay McCutcheon for help with the artwork.

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