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.