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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 4, July/August 2019
226
AFRICA
are reduced in HFpEF patients, although EF is within normal
limits.
9-13
Therefore, the systolic function cannot be considered
normal in these patients.
The loss of longitudinal function may be compensated for by
increased radial motion, which may preserve the EF in HFpEF
patients; an effect that is also seen in diabetic patients.
22
The Sm
velocity was shown to be a prognostic marker in patients with
systemic hypertension and left ventricular hypertrophy, as well
as patients with dilated cardiomyopathy.
23-25
The improvement
in septal tissue Doppler myocardial systolic velocity may be
an important finding of the present study, although it did not
translate into an improvement in EF, likely due to the short
duration of follow up. An improvement in EF also may be
noticed in the long term.
To the best of our knowledge, this study is the first to show
that perindopril treatment improved tissue Doppler systolic
function in HFpEF patients. Improvement in systolic function
may be related to several mechanisms, including reduction in
myocardial fibrosis, left ventricular mass, ischaemia or afterload.
The improvement in tissue Doppler septal late diastolic
velocity may also be another important finding of this study.
Since this velocity represents LA systolic function in HFpEF
patients, perindopril treatment also improved the left atrial
function in these patients. This velocity is not the only way to
assess left atrial function, but it is a practical way to show the
contractile function of the left atrium.
6
Left atrial dysfunction
was associated with exercise intolerance in HFpEF patients,
5
so improving this function may decrease exercise dyspnoea,
which is an important symptom in these patients. We could not
demonstrate symptomatic improvement in our patient group.
Future studies should investigate whether this improvement
in left atrial systolic function is also seen during exercise in these
patients. It may be more crucial to improve exercise left atrial
function since the symptoms are generally exacerbated with
exercise. A longer duration of follow up may also show some
benefit on symptoms.
The median serum NT-proBNP level of the patients recruited
to the present study was 135 pg/ml. This value may be considered
low for an HFpEF diagnosis. In reality, there are not clearly
defined cut-off values for the diagnosis of this syndrome. In the
consensus document of the European Society of Cardiology
(ESC) regarding HFpEF published in 2007, natriuretic peptides
(NPs) were offered to aid the diagnosis when the E/E
′
ratio
was between eight and 15.
26
According to this document, an
NT-proBNP value
>
220 pg/ml supports the diagnosis of
HFpEF, but NT-proBNP
<
120 pg/ml makes the diagnosis
unlikely. In the new 2016 ESC guidelines for heart failure, it
is stated that an NT-proBNP value
>
125 pg/ml supports the
diagnosis of HFpEF.
1
Other studies have also investigated NP levels in DHF
patients. In one of those articles, in patients presenting to the
out-patient clinic (similar to our study), if the patient’s volume
status was stable or optivolaemic, NP levels in HFpEF patients
may be much lower.
27
A different study that enrolled 159 HFpEF
patients reported that 29% of the patients had normal BNP
values (
≤
100 pg/ml). These patients were symptomatic and had
elevated pulmonary capillary wedge pressures.
28
The authors
found that patients with normal BNP levels were younger, were
more often female, were mostly obese and had higher BMIs.
They concluded that a normal BNP level did not exclude an
out-patient diagnosis of HFpEF. Obesity is known to reduce
serum NT-proBNP levels, and this trend should be kept in mind
when considering a diagnosis of HFpEF. NP levels decline
linearly with increasing BMI, and low NP cut-off values should
be used for the diagnosis of HFpEF when BMI is increased.
29,30
In our study, the average BMI of the patients was 33 kg/
m
2
, which might have reduced the NT-proBNP levels. On the
other hand, some drugs, such as diuretics and beta-blockers
31
are
known to diminish serum NT-proBNP levels.
At the baseline of the present study, 54% of the patients
were on diuretic drugs and 35% used beta-blockers. Therefore,
concomitant drug use may be an additional factor that decreased
baseline NT-proBNP levels. Nevertheless, we believe that the
patients we recruited for this study had HFpEF. Framingham
criteria were used to diagnose HF, and all patients were required
to have evidence of DD on echocardiography, which is an
important component of this disease. Another supporting fact
not reported in the results section was that 24% of the patients in
this study were hospitalised or presented to the emergency room
because of HF decompensation during the follow-up period.
These data, which are close to the number of hospitalisations
characteristic to this population, provide another clue that our
patients truly had HFpEF.
32
Study limitations
There are many limitations of our study that are worth
addressing. First of all, many patients discontinued the study
drug or withdrew from the study. Seventeen patients, accounting
for 16% of the total study population (20 patients, when three
patients who died are also included), were excluded from the
study after randomisation due to different reasons. This number
may be large for this type of small-size study. The follow-up
period may also have been too short to accurately investigate the
outcomes associated with the study drug. Over a longer period,
the study drug might have shown more pronounced benefits in
HFpEF patients. LA systolic function was assessed by tissue
Doppler annular late diastolic velocities. This method provides
a rapid way to assess LA systolic function, but it might be
more accurately assessed by LA systolic strain or LA emptying
fraction methods.
Conclusion
Tissue Doppler septal late diastolic velocity and septal systolic
myocardial velocity were increased in the perindopril group.
NT-proBNP level and NYHA functional status were not
changed in this study population.
References
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Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG,
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Eur J Heart Fail
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Persson H, Lonn E, Edner M, Baruch L, Lang CC,
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