Discussion
CF is known to affect cardiac function. Systolic and diastolic LV
dysfunction in CF patients has been well characterized. TTE evaluation
in M-mode and Doppler echocardiography generally shows normal results in
the early stages of cardiac involvement. This cardiac dysfunction in its
subclinical stage may be characterized using methods such as TDI and
STE. While TDI provides global parameters of ventricular function, STE
may be used to selectively evaluate areal ventricular function. STE thus
provides superior evaluation quality compared to TDI (10,11,12).
The baseline assessment in our study used physical examination, ECG and
TTE. Systolic and diastolic LV functions were evaluated by TTE, Doppler,
TDI and STE. While ventricular function as assessed by TTE appeared to
be normal in all cases, pathologic findings of systolic and diastolic
function were revealed by TDI and STE. Three recently published reports
evaluate ventricular function in CF patients using STE. Two of these
studied LV and RV function in adults; the third reports RV function in
children as measured by TDI, strain and strain rate. All three studies
compared TDI to STE. While ventricular function appeared to be normal in
TTE, both techniques gave results confirming subclinical ventricular
dysfunction (5,8,10).
PAPs as measured based on the tricuspit regurgitation (TR) jet was
higher in the CF patients group than in controls. In their study of 35
adult CF patients with a mean age of 27.14 years, Thomas et al.found similarly high PAPs values (1). In this study, 13 patients
diagnosed with pulmonary hypertension were found to have a PAPs higher
than 35 mmHg. In our study, 6 of the CF patients had a PAPs value
exceeding 35 mmHg. Özçelik et al. found the PAPs of pediatric CF
patients (n=18, mean age 7.7) to be normal (8). LV compression by RV
pressure elevation and an abnormal interventricular septal motion may
also affect LV function (5).
In their report of an evaluation by TDI of the LV function of 8 patients
with an average age of 35, Sellers et al . find a higher IVRT in
CF patients compared to controls (10). While S-wave velocities may
appear to be reduced in the patient group relative to the controls, no
statistical significance was detected. The IVRT increase and S-wave
velocity reduction in our CF patients was similarly not confirmed as
statistically significant. TDI studies in CF patients have often been
conducted in adult populations. The studies focused mainly on the IVRT
increase and reduction in S-wave velocities. Özçelik et al. , who
also evaluated LV function by TDI, could not detect a statistically
significant difference between CF patients and controls with regard to
E/A and E/e’ ratios and the MPI. While our results were similar for E/A
and E/e’, a clear difference between patients and control subjects was
evidenced for MPI, which was higher in the CF patients. MPI is a global
indicator of LV function. It increases with the development of LV
dysfunction. We interpreted it as an indicator of LV dysfunction.
STE is a new technique for evaluating ventricular function. The use of
strain and strain rate parameters to evaluate regional deformation is an
alternative to conventional echocardiography. Strain here expresses the
percent dimensional deformation occurring in the object, while strain
rate is the velocity of such deformation. Published reports have shown
the superiority of these parameters over TTE and TDI in identifying
ventricular dysfunction. This technique also seems superior to others in
evaluating local ventricular function in addition to the global one
(15,16,17).
In 41 patients with a mean age of 24, Labombarda et al. used
strain and strain rate to evaluate LV free wall and septal function (5).
They found free wall strain and strain rate and septal strain values to
be significantly lower in patients compared to control subjects. While
also appearing lower, the septal strain rate values were not
significantly different than those of the controls. Sellers et
al. compared peak systolic strain and strain rates in LV STE studies of
adult CF patients to reference values and found them to be lower (10).
We did a similar evaluation of LV strain and strain rate. While the two
published STE reports evaluated ventricular function globally, our study
was different in that it additionally measured local LV function. Of
longitudinal myocardial strain measurements, APS and apex segments in
A4C view, MIL and BAS in A3C, MI, API and MA in A2C were significantly
reduced compared to controls. As for circumferential myocardial strain
measurements, the API segment in the apical, the MI segment in the
medial and the BI segment in the basal view were also significantly
lower than in control subjects. While global and total global strain
values appeared to be lower in 6 windows, this difference was not
confirmed by a detected statistical significance. A statistically
significant reduction was established in CF patients in five segments
(MAL, BIL, MI, apex, APA) in the longitudinal, and five (BAS, BAL, MA,
MIL, MIS) in the circumferential strain rate measurements.
LV dysfunction detected by TDI and STE in CF patients is attributed to
different causes, primarily chronic hypoxia, chronic inflammation,
myocardial fibrosis and RV dysfunction (5,18,19). LV compression by a
dilated RV and interventricular septal motion abnormalities may also be
counted as additional causes of this LV dysfunction. Elevated plasma
angiotensin II and aldosterone levels may also be observed in CF
patients. As a result, myositis with fibroblastic cell proliferation and
an increased protein synthesis leading directly to myocardial fibrosis
may develop. Angiotensin-converting enzyme inhibitors and angiotensin II
receptor antagonists may thus be included in treatment plans (5,18,19).
The CFTR has been characterized in myositis; it has a regulatory
function on resting potentials, calcium-mediated depolarization and
beta-adrenergic stimulation. Disruption of regulation mechanisms at the
cellular level due to CFTR gene defects creates a favorable background
for cardiac dysfunction (9,22). Hyperglycemia, which develops in 32% of
CF patients over age 25 as a result of pancreatic beta-cell damage, may
lead to myocardial function impairment through an increase in myocardial
stiffness and impaired contractility caused by the increased protein
glycosylation (20,21).
As CF patients benefit from an increased life expectancy thanks to
effective treatment and lung transplantation, problems of myocardial
dysfunction may be expected to be increase in frequency. Myocardial
dysfunction in its subclinical stage may be characterized using methods
such as TDI and STE. The ease of use of both these techniques and the
availability of reference values may suggest their possible use in the
follow-up of CF patients. Further studies are needed to determine
whether these findings have clinical significance.
Study Limitations
Our study has several limitations. The first was the impossibility of
using the STE software available to us to evaluate the three-dimensional
structure of RV geometry, while RV dysfunction is the main focus in CF.
The second was that the number of subjects was small. Finally, invasive
hemodynamic data, exercise testing and cardiac MRI were not available at
the same time for correlation with the echocardiographic measurements.
Contributors TD,SI is the guarantor of this work and, as such, had full
access to all the data in the study and takes responsibility for the
integrity of the data and the accuracy of the data analysis. OK wrote
the manuscript and researched data. NU, NY and NU reviewed/edited the
manuscript. OK and MK performed the echocardiographic evaluation.