Summary
Background
Hyperthyroidism is an important cardiovascular risk factor in the development of atrial fibrillation and heart failure. Increased atrial electromechanical intervals are used to predict atrial fibrillation, measured by tissue Doppler imaging (TDI).
Aims
To evaluate atrial electromechanical delay (EMD) and left atrial (LA) mechanical function in patients with overt hyperthyroidism.
Methods
Thirty-four patients with overt hyperthyroidism and 34 controls were included. A diagnosis of overt hyperthyroidism was reached with decreased serum thyroid-stimulating hormone (TSH) and increased free T4 (fT4) concentrations. Using TDI, atrial electromechanical coupling (PA) was obtained from the lateral mitral annulus (PA lateral), septal mitral annulus (PA septum) and right ventricular tricuspid annulus (PA tricuspid). LA volumes (maximum, minimum and presystolic) were measured by the disks method in apical four-chamber view and indexed to body surface area. LA active and passive emptying volumes and fractions were calculated.
Results
LA diameter was significantly higher in hyperthyroid patients ( P = 0.001). LA passive emptying volume and fraction were significantly decreased in hyperthyroid patients ( P = 0.038 and P < 0.001). LA active emptying volume and fraction were significantly increased in hyperthyroid patients ( P < 0.001 and P < 0.001). Left and right intra-atrial (PA lateral–PA septum and PA septum–PA tricuspid) and interatrial (PA lateral–PA tricuspid) EMDs were significantly higher in hyperthyroid patients (29.2 ± 4.4 vs 18.1 ± 2.6, P < 0.001; 18.7 ± 4.3 vs 10.6 ± 2.0, P < 0.001; and 10.5 ± 2.9 vs 7.1 ± 1.2, P < 0.001, respectively). Stepwise linear regression analysis demonstrated that fT4 and TSH concentrations were independent predictors of interatrial EMD (β = 0.436, P < 0.001 and β = –0.310, P = 0.005, respectively).
Conclusion
This study showed prolonged atrial electromechanical intervals and impaired LA mechanical function in patients with overt hyperthyroidism, which may be an early sign of subclinical cardiac involvement and dysrhythmias in overt hyperthyroidism.
Résumé
Objectif
L’hyperthyroïdie est un facteur de risque important de développement d’une fibrillation atriale (FA) et d’insuffisance cardiaque. L’augmentation des intervalles électromécaniques atriaux, prédisant la FA sont mesurées en Doppler tissulaire (DTI). L’objectif de cette étude est d’évaluer le délai électromécanique auriculaire (EMD) et la fonction mécanique auriculaire gauche (OG) chez des patients hyperthyroïdiens.
Méthode
Trentre-quatre patients en hyperthyroïdie et 34 témoins ont été inclus. Le diagnostic d’hyperthyroïdie a été retenu sur une diminution de la concentration en TSH et une augmentation de la T4 libre (fT4). En utilisant le DTI, le couplage électromécanique auriculaire (PA) a été mesuré à l’anneau mitral latéral (PA latéral), à l’anneau mitral septal (PA septum) et à l’anneau tricuspide (PA tricuspide). Les volumes auriculaires gauches (maximum, minimum et présystolique) ont été mesurés par la méthode des disques, en incidence apicale des quatre cavités, et indexés à la surface corporelle. Les volumes de vidange de l’oreillette gauche lors des phases active et passive ainsi que les fractions ont été calculées.
Résultats
Le diamètre de l’oreillette gauche est significativement plus important chez les patients hyperthyroïdiens ( p = 0,001). Le volume de vidange passif auriculaire gauche et la fraction étaient significativement diminués chez les patients hyperthyroïdiens ( p = 0,038 et p < 0,001). Le volume de vidange actif auriculaire gauche et la fraction étaient significativement augmentés chez les hyperthyroïdiens ( p < 0,001 et p < 0,001). Les délais intra-atriaux auriculaire gauche et droit (PA latéral – PA septum et PA septum – PA tricuspide, respectivement) ainsi que les délais inter-atriaux (PA latéral – PA tricuspide). Les délais électromécaniques auriculaires étaient significativement plus élevés chez les hyperthyroïdiens (29,2 ± 4,4 versus 18,0 ± 2,6, p < 0,001 ; 18,7 ± 4,3 versus 10,6 ± 2,0, p < 0,001 ; et 10,5 ± 2,9 versus 7,1 ± 1,3, p < 0,001). L’analyse par régression linéaire a montré que la T4 libre et la concentration en TSH étaient des prédicteurs indépendants du délai électromécanique atrial dans sa composante inter-auriculaire (β = 0,388, p = 0,001 et β = 0,547, p < 0,001).
Conclusion
Cette étude montre que les intervalles électromécaniques auriculaires sont prolongés et que la fonction mécanique auriculaire gauche est altérée chez le patient hyperthyroïdien. L’allongement des intervalles électromécaniques et l’altération de la fonction mécanique auriculaire gauche pourraient être un signe précoce d’une atteinte cardiaque infra-clinique et de risque accru d’arythmie chez des patients hyperthyroïdiens.
Background
Thyroid hormone receptors are highly expressed in the myocardium . Consequently, overt hyperthyroidism has profound cardiac effects, including increased heart rate, arrhythmias, LV diastolic dysfunction , LV systolic dysfunction , decreased systemic vascular resistance and the development of atrial fibrillation and heart failure . Hyperthyroidism can lead to decreased diastolic function as a result of impaired myocardial relaxation . Moreover, hyperthyroidism is associated with LV diastolic dysfunction due to decreased myocardial relaxation and inhibited rapid ventricular filling, both at rest and with exercise ; this is frequently related to a changeable impairment of LV systolic function. Thus, hyperthyroidism may result in significant cardiovascular alterations, including atrial fibrillation and heart failure .
In a study, the atrial systolic time interval, atrial ejection time and atrial pre-ejection period were used to evaluate atrial function. In addition, the relationship between hyperthyroidism and atrial function was examined . LA volume and mechanical function has recently been identified as a potential indicator of cardiac disease and arrhythmias . Inter- and intra-atrial conduction disorders are well-known electrophysiological distinctions of atria prone to fibrillation . Unlike LA size, atrial conduction time reflects the levels of both electrical and structural remodelling of the atria. All of these variables are similar and result in impaired atrial function .
Alterations in thyroid status may lead to changes in both ventricular and atrial function. However, LA mechanical function and atrial conduction abnormalities have not been investigated in overt hyperthyroidism. The aim of the present study was to evaluate atrial electromechanical delay and LA mechanical function in patients with overt hyperthyroidism.
Methods
Study population
We studied 34 newly treated or untreated patients, previously diagnosed with overt hyperthyroidism (25 women and nine men; mean age 45.2 ± 9.3 years). The control group consisted of 34 sex- and age-matched healthy subjects (24 women and ten men; mean age of 43.6 ± 8.0 years) who were free of endocrinological, inflammatory, connective tissue, cardiovascular, pulmonary and other known systemic disease, and were admitted to hospital for a check-up. All subjects in the study population had normal sinus rhythm on ECG. The study was designed as cross-sectional.
A diagnosis of overt hyperthyroidism was reached with decreased serum TSH concentrations, increased fT4 concentrations and/or increased fT3 concentrations in fasting blood samples (normal values in our laboratory were: 0.4–4.0 mIU/mL for TSH; 0.89–1.76 ng/dL for fT4; and 1.80–5.00 pg/mL for fT3). Demographic characteristics, biochemical variables, lipid values and ECGs were obtained for the entire study population. Exclusion criteria were as follows: subclinical hyperthyroidism, acute coronary syndrome, prior myocardial infarction and coronary artery disease, congestive heart failure, LV hypertrophy, prolonged QRS duration (≥ 120 ms), reduced LV ejection fraction (< 55%), atrial flutter or fibrillation, significant valvular heart disease, pacemaker implantation, frequent ventricular pre-excitation and atrioventricular conduction abnormalities, diabetes mellitus, arterial hypertension (resting blood pressure ≥ 140/90 mmHg), medications known to alter cardiac conduction, peripheral vascular disease, congenital heart disease, pulmonary or neurological disease, pericarditis, peripheral neuropathy, alcohol abuse, renal or hepatic disease and poor echocardiographic imaging. Approval for the study was obtained from the local ethics committee and all subjects gave informed consent.
Standard echocardiography
At study entry, all patients were evaluated by transthoracic, M-mode, 2D, pulsed-wave, continuous-wave, colour-flow and TDI. Echocardiographic examinations were performed with the GE Vivid-7 system (GE Vingmed, Horten, Norway) with a 2–4 MHz transducer at a dept of 16 cm. During echocardiography, a continuous single-lead ECG recording was obtained. All patients were imaged in the left lateral decubitus position. 2D and conventional Doppler examinations were obtained in the parasternal and apical views according to the guidelines of the American Society of Echocardiography . LV diameters and wall thickness were measured by M-mode echocardiography. LV ejection fraction was calculated using the apical two-and four-chamber views by Simpson’s method, according to American Society of Echocardiography guidelines . The mitral valve inflow pattern (E-wave, A-wave, E-wave deceleration time, E/A ratio and isovolumic relaxation time) were measured using pulsed-wave Doppler. LV mass index was calculated using the Devereux equation . LA volumes were obtained echocardiographically from the apical four-chamber views by the disks method . LA Vmax at the end-systolic phase (onset of the mitral opening), LA Vmin at the end-diastolic phase (onset of the mitral closure) and Vp were measured at the beginning of atrial systole (onset of P wave on ECG) and indexed to BSA. LA function variables were calculated as follows: LA passive emptying volume = Vmax–Vp; LA passive emptying fraction = ([Vmax–Vp]/Vmax) × 100%; LA active emptying volume = Vp–Vmin; LA active emptying fraction = ([Vp–Vmin]/Vp) × 100% .
Atrial electromechanical interval
TDI was performed using transducer frequencies of 3.5 to 4.0 MHz, adjusting the spectral pulsed Doppler signal filters to acquire the Nyquist limit of 15 to 20 cm/s and using the minimal optimal gain. Myocardial TDI velocities (Sm, Em and Am velocities) were measured via spectral pulsed Doppler of the LV free wall from the apical four-chamber view . The ultrasound beam was positioned as parallel as possible to the myocardial segment to acquire the optimal angle of imaging. The monitor sweep speed was set at 50 to 100 mm/s to optimize the spectral display of myocardial velocities. The time interval from the P wave onset on the surface ECG to the beginning of the Am is defined as PA; it was obtained from the lateral mitral annulus, the septal mitral annulus and the right ventricular tricuspid annulus, and named PA lateral ( Fig. 1 ), PA septum, and PA tricuspid, respectively. The difference between PA lateral and PA tricuspid was defined as the EMD, the difference between PA lateral and PA septum was defined as the left intra-atrial EMD and the difference between PA septum and PA tricuspid was defined as the right intra-atrial EMD . All measurements were repeated three times and average values were obtained for each of the atrial conduction delay times. All measurements were performed by two experienced investigators who were unaware of the subject’s clinical status.
Reproducibility
Intraobserver variability was evaluated in 20 subjects selected randomly from the study population by repeating the measurements under the same basal conditions. To test inter-observer variability, the measurements were performed offline from video recordings by a second observer. Reproducibility of atrial electromechanical coupling and LA volumes obtained by 2D echocardiography were evaluated by the coefficient of variation between measurements.
Intraobserver variability was 4.1% for PA lateral, 4.5% for PA septum, 4.8% for PA tricuspid, 4.7% for Vmax, 4.3% for Vp and 4.7% for Vmin. Inter-observer variability was 4.0% for PA lateral, 4.3% for PA septum, 4.5% for PA tricuspid, 4.9% for Vmax, 4.6% for Vp and 4.5% for Vmin.
Statistical analysis
All analyses were performed using the SPSS (SPSS for Windows 15.0) software package. Continuous variables are presented as means ± standard deviations. Categorical variables are presented as percentages. The chi-square test was used for categorical variables and the unpaired t test was used for continuous variables. Pearson’s correlation coefficient was used for correlation analysis. A stepwise multiple regression analysis was used to recognize the significant determinants of interatrial EMD, which incorporated variables that correlated with a value of P < 0.1 in the correlation analysis. A value of P < 0.05 was considered statistically significant.
Results
Patient characteristics
The clinical and laboratory characteristics and echocardiographic findings for the two groups are shown in Table 1 . Age, sex, smoking, systolic and diastolic blood pressure, LV end-diastolic and end-systolic diameters, LV mass index and LV ejection fraction were similar in the two groups ( P > 0.05). BMI and BSA were significantly lower in hyperthyroid patients ( P = 0.023 and P = 0.001, respectively). So, as expected, hyperthyroid patients had significantly lower TSH and higher fT4 and fT3 concentrations compared with controls. Heart rate and LA diameter were significantly higher in hyperthyroid patients than in controls ( P = 0.001 and P = 0.001, respectively). Also, Am velocity, Em/Am and E/E’ ratio were significantly lower in hyperthyroid patients ( P = 0.035, P = 0.004 and P = 0.002, respectively).
