Cardiovascular Journal of Africa: Vol 28 No 5 (September/October 2017)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 28, No 5, September/October 2017

AFRICA

283

There are a number of studies that have evaluated the effects

of individual drugs in degenerative MR. Most of these involved

beta-blockers or vasodilators.

12,43

The results from these mostly

small, non-randomised trials were inconclusive.

10,44

The effect

of aldosterone receptor antagonists has not been evaluated in

organic MR in humans. Additionally, no trial has systematically

explored the effects of combination therapy (with or without

HF), secondary to CRMR.

In our study, lack of benefit from individual agents may have

been due to incomplete blockade of the sympathetic nervous

system (SNS) or the RAAS. An example would be that of

aldosterone escape during prolonged ACE inhibitor therapy.

Other possibilities include activation of the kallikrein–kinin

system due to an increase in bradykinin, which in turn activates

matric metalloproteinases, resulting in collagen loss, a process

that may be exacerbated by the inhibition of angiotensin II by

ACE inhibitors.

These drugs in combination have synergistic action; for

example the combination of an ACE inhibitor, beta-blocker

and aldosterone receptor antagonist suppresses myocardial

fibrosis in systolic heart failure.

Therefore, combination therapy

with drugs that block the SNS and RAAS systems may be

the answer. Most of our patients were on a combination of

carvedilol, spironolactone and an ACE inhibitor. However, their

effect on left ventricular function and rheumatic MR severity

remains questionable.

All the patients however remained stable on combined

medical therapy and none was hospitalised for HF or died

during the six months of follow up. This is a relevant finding

as more than 50% of patients with all-cause systolic HF

are re-hospitalised within six months of HF assessment.

The lack of sudden cardiac death and HF-related deaths

in this study may be attributed to medical treatment, or

perhaps chance, due to the small sample size. Combined

medical therapy may serve to stabilise the disease process,

probably via neuro-hormonal modulation (likely the most

important compensatory and deleterious mechanism in

MR).

Combination HF therapy may therefore serve as

a bridge to surgery, given the long delays due to resource

limitations, or as a substitute for surgery where patients

decline surgery or have a high surgical risk due to severe

ventricular dysfunction.

There were several limitations to this observational study.

We had no control arm, there was a varied combination of

medications, the exact duration of therapy at baseline was not

clear due to incomplete records, the study subjects and the

researchers were not blinded to the treatment, it was a small

sample size, and the follow-up period was short.

Conclusion

We have shown that combination anti-remodelling medical

therapy in CRMR may be beneficial to prevent hospitalisation

for HF and death. It may have a stabilising effect on HF

secondary to chronic rheumatic MR. Further larger studies

are needed to test the effect of combination therapy on chronic

organic MR.

Dr Meel was the recipient of the Carnegie PhD Fellowship award (Carnegie

Corporation Grant No. b8749.r01).

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