Methods
This case-control study was conducted on 26 newly diagnosed and
untreated hyperthyroid patients in comparison to 26 healthy. Also, age
and sex were matched in subjects as control group in Rajaie Heart center
echo lab. Patients were referred to us from out-patient clinic of
Loghman Hakim Hospital endocrinology department. The recruitment phase
was done from January 2019 to January 2020, and the patients who were
diagnosed with hyperthyroid based on clinical and laboratory data, had
no history of hypertension, diabetes mellitus, cardiovascular disease,
hyperlipidemia, anemia, pulmonary, and neuromuscular disease, and take
no medication were entered to the study. Control subjects were chosen
among the people with normal stress echocardiography result who came to
our echo lab for checkup or non-anginal chest pain and had no past
medical history with normal lab test for thyroid function, lipid
profile, blood sugar, and hemoglobin.
At first, we assessed the patients by electrocardiography (ECG) and
conventional echocardiography, and exclude those who had valvular heart
disease, any structural heart disease, left ventricular (LV) systolic
dysfunction by means of LV ejection fraction of less than 55% by
Simpson method, pulmonary hypertension (systolic pulmonary artery
pressure more than 35mmHg using tricuspid regurgitation (TR) velocity),
and non-sinus rhythm. Three of 29 patients who were referred to our
center, were excluded from the study due to LV dysfunction, pulmonary
hypertension, and atrial fibrillation plus LV dysfunction.
Stress echocardiography
A complete two dimensional(2D) and Doppler echocardiography was done by
an experienced operator at the time of resting in left lateral decubitus
position, using the same machine (affinity 70 Philips with 1-5MHz
transducer) in terms of the American society of echocardiography
recommendation. LV end diastolic volume, end systolic volume, and EF
were calculated from apical two and four chamber views based on the
modified Simpson method. Diastolic parameters including mitral inflow
velocities (E and A waves), mitral annulus tissue Doppler velocities
(septal and lateral e’), left atrium volume index (LAVI), and peak TR
velocity were measured by averaging in three consecutive cardiac cycle
to estimate diastolic function in terms of the 2016 ASE
guideline(14). Isovolumic relaxation time
(IVRT) and myocardial performance index (MPI) were also measured using
tissue Doppler method. Then, the patient and control groups underwent an
exercise stress echocardiography on treadmill using Bruce protocol. End
points for exercise were chest pain, dyspnea, exhaustion, target heart
rate of more than 90% adjusted by age, and significant ST segment
deviation. Blood pressure and ECG were recorded at any stage. Peak
stress images including 5 standard echocardiographic views (parasternal
long and short axis views, apical 4 chamber, 3 chamber, and 2 chamber
views) were obtained immediately after cessation of test during one
minute for evaluation of ischemia and speckle tracking strain analysis.
TR peak velocity was obtained within 1 minute from peak stress, and E
and e’ velocities were measured at time of 60-90 milliseconds from peak
when E and A, e’ and a’ waves were not fused in heart rate about 120
beat per minute.
Definition
-Hyperthyroidism was diagnosed when serum free Thyroxin (T4) and
triiodothyronine (T3) were more than upper limit of laboratory range,
and Thyroid stimulating hormone (TSH) was less than 0.1mIU/mL. (T3 and
T4 were measured by radioimmunoassay and TSH by immunometric method
using commercially available kits)
-Based on the ASE guideline, for evaluation of diastolic function in the
patients with preserved EF we considered four criteria including: 1)
septal e’ velocity < 7cm/s or lateral e’<10cm/s, 2)
average E/e’ ratio>14, 3) LAVI>34ml/m2, and 4)
peak TR velocity>2.8m/s. Diastolic function was normal when
more than half of four variables were negative. LV diastolic dysfunction
was present when more than 50% of indices were positive, and diastolic
function was indeterminate if half of parameters were positive.
-Stress echocardiography test was considered to be positive for
diastolic dysfunction when all of following parameters were present in
peak stress: 1) average E/e’>14 or septal
E/e’>15, 2) peak TR velocity>2.8m/s, and 3)
septal e’ velocity<7 cm/s or lateral velocity<10
cm/s at base line.
-IVRT and MPI were calculated by tissue doppler method when myocardial
velocities were recorded using spectral pulse doppler from mitral
annular level in apical 4 chamber view. MPI was calculated as sum of
isovolumic relaxation time and isovolumic contraction time were divided
by ejection time.
Statistical analysis: The results of quantitative variables
with normal distribution were expressed as mean and standard deviation
(mean ± SD), and numerical variables without normal distribution were
expressed as median with inter-quartile range (IQR). Qualitative
variables were reported by number and percentage. To compare the
numerical variables with and without normal distribution, “independent
samples t-test” and “Mann-Whitney U test” were used, respectively.
Also, Chi-Square test was used to compare nominal variables. All the
tests were performed using IBM® SPSS Statistics® v. 22 at 95%
confidence level.