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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 28, No 3, May/June 2017
AFRICA
157
muscle.
19-21
It is well known that impaired endothelial function
plays an important role in the pathogenesis of atherosclerosis,
22
which has been demonstrated in FMF patients.
23
Previous studies investigated vascular and cardiac function
in FMF. Calıskan
et al
.
24
analysed coronary flow reserve by
transthoracic echocardiography and found that coronary
microvascular function and left ventricular diastolic function
were impaired in patients with FMF. This suggests that
an existing inflammatory process also affects the coronary
microvascular tree. In another study, Akdogan
et al.
23
showed
impaired flow-mediated dilatation (FMD) of the brachial artery
in patients with FMF, and impaired FMD has been shown to
be correlated with coronary endothelial dysfunction.
25
Although
the exact mechanisms of arrhythmia in FMF are unknown, the
authors proposed that conduction disturbances and rhythm
disorders could be associated with ongoing inflammation-related
ischaemia and/or focal fibrosis.
Fibrosis in the heart muscle plays an important role in
the pathogenesis of ventricular arrhythmias. Parameters of
autonomic cardiac tone, such as heart rate variability (HRV),
heart rate turbulance (HRT) and QT dynamics, are useful for
risk evaluation for ventricular arrhythmias, and abnormalities
in these parameters may precede the development of fibrosis.
26
To date, subclinical cardiovascular involvement associated
with cardiac autonomic dysfunction in FMF has been reported
in many studies. Fidanci
et al
.
27
demonstrated that one of the
time-domain parameters of HRV calculated and analysed by
24-hour ambulatory electrocardiographic monitoring software
was significantly decreased in patients with FMF compared
to controls. Similarly, Canpolat
et al
.
28
showed abnormal HRV
and HRT values in FMF patients. In light of these studies,
we hypothesised that impaired endothelial function reduced
coronary flow reserve and caused microvascular ischaemia and
inflammation-related fibrosis, which, by affecting ventricular
repolarisation, may lead to arrhythmias in FMF patients.
Myocardial repolarisation is mostly evaluated using
measurements of QT interval and T wave on ECG and it may
be affected by some pathophysiological processes such as genetic
diseases, acquired clinical conditions, and/or drugs.
29,30
Prolonged
QTandQTc intervalsmay be caused by life-threatening ventricular
arrhythmias, such as polymorphic ventricular tachycardia,
torsades de pointes, and ventricular fibrillation.
31
Several investigators have evaluated QT and QTc intervals in
inflammatary diseases. In a study by Acar
et al
.,
32
they reported
a similar QT interval but significantly longer maximum QTc
interval only in rheumatoid arthritis patients compared to control
subjects. In another study, Akcay
et al
.
6
showed statistically
significantly longer maximum QT and maximum QTc intervals
only in FMF patients. In the same study,
33
FMF patients had
similar QT and QTc intervals compared with healthy controls. In
our study, QT and QTc intervals were similar between the groups.
QTd is the most frequently used parameter to detect the
dispersion of ventricular repolarisation and is accepted as a
marker for arrhythmia and sudden death.
34
QTd is superior to QT
and QTc intervals in the assessment of ventricular arrhythmias.
It has been demonstrated that a prolonged QTd is associated
with an increased risk of ventricular arrhythmias in patients
with hypertrophic cardiomyopathy and long-QT syndrome.
35,36
Previous studies have shown that QTd was significantly higher
in some inflammatory diseases.
32,37
A number of studies have investigated the effect on QTd
of systemic inflammation in patients with FMF. Akcay
et al.
6
showed that QTd was increased in FMF patients. On the other
hand, in another study by Giese
et al
.,
35
they evaluated the QTd
values in 30 FMF patients and found similar findings between
FMF patients and healthy controls. We also found the QTd
values were similar between the two groups.
Tp-Te interval is a new index of dispersion of myocardial
repolarisation, which is related to ventricular arrhythmogenesis
and sudden cardiac death.
10,38
Several investigators showed that
the Tp-Te interval is longer in disorders such as long-QT and
Brugada syndromes.
11
Yamaguchi
et al.
39
reported that the Tp-Te
interval was more significant than QT dispersion in predicting
torsade de pointes in patients with acquired long-QT syndrome.
Increased Tp-Te interval may also be a predicting index
for elevated risk of cardiovascular mortality in inflammatory
diseases. It was reported that the Tp-Te interval was prolonged
in patients with rheumatoid arthritis and systemic lupus
erythematosus.
32,37
In another study, Akcay
et al
.
6
reported that
the Tp-Te interval was increased in FMF patients. Similar to
that study, we found that the Tp-Te interval was statistically
significantly prolonged in FMF patients.
Tp-Te interval is affected by variations in heart rate and body
weight.
15
Recently, the cTp-Te interval and cTp-Te/QT ratio were
suggested to be more accurate measurements of the dispersion
of myocardial repolarisation, compared to the QT, QTd, and
Tp-Te intervals. In our study, we found significant differences in
the cTp-Te interval and cTp-Te/QT ratio between FMF patients
and control subjects. In the light of these data, we evaluated
the effect of inflammatory markers on the cTp-Te interval in
FMF patients and found that prolonged Tp-Te was positively
correlated with ESR and CRP levels and NLR. In addition, we
found that ESR was an independent predictor of a prolonged
cTp-Te interval in patients with FMF.
Our study has several limitations. The major limitation is the
small size of the study population and it may have negatively
affected the statistical results. Second, the study had a cross-
sectional design and there was no follow up of arrhythmic
episodes in patients.
Conclusions
The findings of this study demonstrate that increased cTp-Te
interval and cTp-Te/QT ratio may create a specific risk for
ventricular arrhythmias in patients with FMF. However, the
underlying mechanism and prognostic effects are as yet unknown.
Therefore larger, long-term prospective and multicentre follow-
up studies are needed.
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