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1.  Left ventricular filling characteristics in pulmonary hypertension: a new mode of ventricular interaction 
British Heart Journal  1992;68(1):16-20.
Objective—To examine the effects of pulmonary hypertension on left ventricular diastolic function and to relate the findings to possible mechanisms of interdependence between the right and left sides of the heart in ventricular disease.
Design—A retrospective and prospective analysis of echocardiographic and Doppler studies.
Setting—A tertiary referral centre for both cardiac and pulmonary disease.
Patients—29 patients with pulmonary hypertension (12 primary pulmonary hypertension, 10 pulmonary fibrosis, five atrial septal defect (ASD), and two scleroderma) were compared with a control group of 10 patients with an enlarged right ventricle but normal pulmonary artery pressure (six ASD, one after ASD closure, one ASD and pulmonary valvotomy, one tricuspid valve endocarditis and repair, and one pulmonary fibrosis). None had clinical or echocardiographic evidence of intrinsic left ventricular disease.
Main Outcome measures—M mode echocardiographic measurements were made of septal thickness, and left and right ventricular internal cavity dimensions. Doppler derived right ventricular to right atrial pressure drop, and time intervals were measured, as were isovolumic relaxation time, and Doppler left ventricular filling characteristics.
Results—The peak right ventricular to right atrial pressure gradient was (mean (SD)) 60 (16) mm Hg in pulmonary hypertensive patients, and 18 (5) mm Hg in controls. The time intervals P2 to the end of the tricuspid regurgitation, and P2 to the start of tricuspid flow were both prolonged in patients with pulmonary hypertension compared with controls (115 (60) and 120 (40) ν 40 (15) and 45 (10) ms, p values <0·001). Pulmonary hypertensive patients commonly had a dominant A wave on the transmitral Doppler (23/29); however, all the controls had a dominant E wave. Isovolumic relaxation time of the left ventricle was prolonged in pulmonary hypertensive patients compared with controls, measured as both A2 to mitral valve opening (80 (25) ν 50 (15) ms) and as A2 to the start of mitral flow (105 (30) ν 60 (15) ms, p values <0·001). The delay from mitral valve opening to the start of transmitral flow was longer in patients with pulmonary hypertension (30 (15) ms) compared with controls (10 (10) ms, p < 0·001). At the time of mitral opening there was a right ventricular to right atrial gradient of 12 (10) mm Hg in pulmonary hypertensive patients, but this was negligible in controls (0·4 (0·3) mm Hg, p < 0·001).
Conclusions—Prolonged decline of right ventricular tension, the direct result of severe pulmonary hypertension, may appear as prolonged tricuspid regurgitation. It persists until after mitral valve opening on the left side of the heart, where events during isovolumic relaxation are disorganised, and subsequent filling is impaired. These effects are likely to be mediated through the interventricular septum, and this right-left ventricular asynchrony may represent a hitherto unrecognised mode of ventricular interaction.
PMCID: PMC1024963  PMID: 1515286
2.  Doppler-derived velocity of blood flow across the cardiac valves in the normal dog. 
Doppler echocardiography is a relatively new procedure used to assess certain cardiovascular disorders in the dog. The objectives of this study were to determine the range of values for the maximal peak velocity of blood flow across each of the four cardiac valves in a sample population of normal adult dogs, using duplex continuous wave Doppler echocardiography, and to determine the optimal tomographic planes to use for an adequate continuous wave Doppler evaluation of the canine heart. Twenty normal dogs were examined to obtain values for peak transvalvular velocity for each of the four cardiac valves. The mean values +/- 1 SD, in cm/s were: 98.1 +/- 9.4 for the pulmonary valve imaged from the left side of the chest, 95.5 +/- 10.3 for the pulmonary valve imaged from the right side of the chest (n = 19), 118.1 +/- 10.8 for the aortic valve, 86.2 +/- 9.5 for the mitral valve and 68.9 +/- 8.4 for the tricuspid valve. Regurgitation was detected across the pulmonic valve in 14 of the 20 dogs, and across the tricuspid valve in ten dogs. The analysis of the tomographic images confirmed that for a complete assessment of a given intracardiac valve, the valve must be examined from all possible directions to obtain maximum values for peak velocity.
Images
PMCID: PMC1263441  PMID: 1884300
3.  Comparisons between female and male patients with mitral stenosis. 
British Heart Journal  1994;72(6):567-570.
OBJECTIVE--To compare Doppler, echocardiographic, and clinical variables in female and male patients with mitral stenosis. DESIGN--Observational study in consecutive patients with mitral stenosis of cross sectional and Doppler echocardiographic and clinical variables and a retrospective search for a history of systemic embolism. SETTING--A medical centre with 3000 beds, serving both urban and rural populations. PATIENTS--500 consecutive patients with an echocardiographic mitral valve area of 2 cm2 or less. 331 (66.2%) were female and 169 (33.8%) male (mean (SD) ages of 49 (13) and 48 (14) respectively). MAIN OUTCOME MEASURES--Mitral valve areas by echocardiographic planimetry and Doppler pressure half-time method, peak early diastolic mitral velocity and pressure gradient, echocardiographic score of mitral valve, left atrial end systolic diameter, frequency of left atrial thrombus and smoky echoes as well as various valve lesions detected with Doppler and echocardiography, cardiac rhythm, symptomatic functional class of heart failure, and history of systemic embolism. RESULTS--The prevalence of significant tricuspid (22% v 9%, P < 0.001) and pulmonary regurgitation (5% v 1%, P = 0.018) was higher in the female patients than in the male patients. Female patients also had a higher peak regurgitant velocity (3.2 (0.7) v 2.9 (0.7) m/s, P = 0.007) and pressure gradient (41 (21) v 36 (19) mm Hg, P = 0.010) across the tricuspid valve. However, the male patients had a higher echocardiographic score (9.7 (2.4) v 7.0 (2.3), P < 0.001) and a smaller Doppler-derived mitral valve area (0.9 (0.4) v 1.0 (0.4) cm2, P = 0.027). There were no differences between the female and the male patients in mitral valve area measured by planimetry, peak early diastolic mitral velocity and pressure gradient, and left atrial end systolic diameter or in the prevalence of atrial fibrillation, left atrial thrombus, left atrial smoky echoes, significant aortic stenosis, aortic regurgitation, or heart failure of New York Heart Association class III or IV. CONCLUSIONS--Female patients not only had a higher prevalence of mitral stenosis but also had a higher prevalence of associated tricuspid and pulmonary regurgitation along with a higher velocity and gradient of tricuspid regurgitation. The echocardiographic score was higher in male patients, however. These findings suggest that the pathophysiology of mitral stenosis is different in the two sexes and that gender should be taken into account when therapeutic strategies are formulated.
PMCID: PMC1025644  PMID: 7857741
4.  Transthoracic echocardiography reference values in juvenile and adult 129/Sv mice 
Background
In the recent years, the use of Doppler-echocardiography has become a standard non-invasive technique in the analysis of cardiac malformations in genetically modified mice. Therefore, normal values have to be established for the most commonly used inbred strains in whose genetic background those mutations are generated. Here we provide reference values for transthoracic echocardiography measurements in juvenile (3 weeks) and adult (8 weeks) 129/Sv mice.
Methods
Echocardiographic measurements were performed using B-mode, M-mode and Doppler-mode in 15 juvenile (3 weeks) and 15 adult (8 weeks) mice, during isoflurane anesthesia. M-mode measurements variability of left ventricle (LV) was determined.
Results
Several echocardiographic measurements significantly differ between juvenile and adult mice. Most of these measurements are related with cardiac dimensions. All B-mode measurements were different between juveniles and adults (higher in the adults), except for fractional area change (FAC). Ejection fraction (EF) and fractional shortening (FS), calculated from M-mode parameters, do not differ between juvenile and adult mice. Stroke volume (SV) and cardiac output (CO) were significantly different between juvenile and adult mice. SV was 31.93 ± 8.67 μl in juveniles vs 70.61 ± 24.66 μl in adults, ρ < 0.001. CO was 12.06 ± 4.05 ml/min in juveniles vs 29.71 ± 10.13 ml/min in adults, ρ < 0.001. No difference was found in mitral valve (MV) and tricuspid valve (TV) related parameters between juvenile and adult mice. It was demonstrated that variability of M-mode measurements of LV is minimal.
Conclusions
This study suggests that differences in cardiac dimensions, as wells as in pulmonary and aorta outflow parameters, were found between juvenile and adult mice. However, mitral and tricuspid inflow parameters seem to be similar between 3 weeks and 8 weeks mice. The reference values established in this study would contribute as a basis to future studies in post-natal cardiovascular development and diagnosing cardiovascular disorders in genetically modified mouse mutant lines.
doi:10.1186/1476-7120-11-12
PMCID: PMC3651272  PMID: 23634975
Echocardiography; Juvenile; Adult; 129/Sv mouse; Reference values; Doppler
5.  Right ventricular filling in dilated cardiomyopathy. 
British Heart Journal  1995;74(3):287-292.
PURPOSE--To assess right ventricular filling in dilated cardiomyopathy. PATIENTS--32 patients with dilated cardiomyopathy and 24 healthy controls. METHODS--Stroke distances were measured by pulsed Doppler echocardiography at left ventricular outflow and left and right ventricular inflow. The inflow tract dimensions of both ventricles and the outflow tract dimension of the left ventricle were measured from two dimensional images. Right and left sided atrioventricular (AV) ring excursions were measured by M mode echocardiography at the tricuspid and mitral rings. Stroke volume was derived as stroke distance multiplied by left ventricular outflow tract area. Total stroke distances were calculated as the sum of AV valve Doppler stroke distances and ring excursion. The effective orifice areas of the two AV valves were thus defined as stroke volumes divided by total stroke distance. RESULTS--Total tricuspid stroke distance was normally less than mitral (6.0 (1.7) v 7.6 (1.7) cm, P < 0.05), implying that effective orifice area of the tricuspid valve was consistently greater (6.6 (1.6) v 4.5 (0.8) cm2, P < 0.01). Total tricuspid ring excursion was normally more than mitral (2.30 (0.30) v 1.62 (0.22) cm, P < 0.01). Total tricuspid stroke distance in dilated cardiomyopathy was also less than mitral (7.8 (2.4) v 9.7 (2.8) cm, P < 0.05). Tricuspid stroke distance was significantly increased in patients with dilated cardiomyopathy compared with that in healthy controls (P < 0.05 v controls), though stroke volume was much smaller (26 (10) v 63 (11) ml, P < 0.01) so that tricuspid effective orifice area was reduced to less than half normal (2.7 (1.2) cm2, P < 0.01). Total tricuspid ring long axis excursion was more than mitral (1.37 (0.6) v 0.74 (0.21) cm, P < 0.01). Right ventricular end diastolic inflow dimension was increased compared with that in healthy controls (3.9 (0.7) v 2.8 (0.5) cm, P < 0.01), correlating inversely with tricuspid effective orifice area (r = -0.71, P < 0.01). Total tricuspid ring excursion was bimodally distributed as a low amplitude group (less than 1.6 cm, n = 23) and a high amplitude group (more than 1.6 cm, n = 9), in which the interval P2 to onset of tricuspid flow was much longer (100 (35) v 50 (14) ms, P < 0.01). CONCLUSIONS--Enlargement of the right ventricular inflow tract in dilated cardiomyopathy, especially to more than 5 cm, is accompanied by a progressive decrease in effective tricuspid orifice area, sometimes to less than 1 cm2 and increased inflow velocities. Right ventricular relaxation was incoordinate in 28% of the patients studied. These disturbances of right ventricular filling are likely to compromise overall cardiac function independently of left ventricular disease.
PMCID: PMC484020  PMID: 7547024
6.  Relation of left ventricular isovolumic relaxation time and incoordination to transmitral Doppler filling patterns 
British Heart Journal  1992;68(6):567-573.
Objective—To investigate factors during isovolumic relaxation that determine Doppler filling patterns in patients with left ventricular disease, and thus to identify the underlying mechanisms.
Design—85 patients (50 ischaemic heart disease, 35 left ventricular hypertrophy due to aortic stenosis) and 26 controls were studied with Doppler and M mode echocardiography and phonocardiography. 16 patients underwent two studies on separate occasions, to find whether changes in isovolumic relaxation time were reflected by a change in the Doppler A/E ratio.
Setting—A tertiary cardiac referral centre.
Subjects—Patients referred for assessment of coronary artery disease or aorticstenosis with left ventricular hypertrophy.
Main outcomes measures—Doppler filling velocities during early (E wave) and late (A wave) diastole and the A/E ratio, acceleration of the E wave, digitised M mode indices of incoordinate relaxation (change in cavity dimension before mitral valve opening and time from minimum dimension to mitral valve opening), isovolumic relaxation time, M mode measures of diastolic function after mitral valve opening (peak rate of posterior wall thinning and peak rate of dimension increase), and left ventricular end diastolic pressure.
Results—A/E correlated with age in normal subjects (r = 0·74), to a lesser extent in left ventricular hypertrophy (r = 0·41), but not significantly in ischaemic heart disease. In all patients, isovolumic relaxation time was significantly and negatively correlated with the acceleration of the E wave, showing its fundamental relation to the force responsible for early diastolic filling (r = −0·71 for left ventricular hypertrophy, and −0·74 for ischaemic heart disease, p value < 0·01). In left ventricular hypertrophy and those ischaemic patients without left ventricular dilatation A/E was correlated both with isovolumic relaxation time (r = 0·68 and 0·60 respectively), and with incoordinate relaxation (r = 0·65 and 0·61). In those ischaemic patients with left ventricular dilatation, the influence of incoordination was lost and isovolumic relaxation time became the dominant influence upon A/E (r = 0·82). Weak correlations of end diastolic pressure and RR interval with A/E, became insignificant once isovolumic relaxation time had been taken into account. Isovolumic relaxation time and incoordination together accounted for over 50% of the variance in the A/E ratio in our patients. Isovolumic relaxation time and the A/E ratio were linearly related. Patients with a short isovolumic relaxation time had evidence of considerable diastolic abnormalities, despite a normal Doppler A/E ratio. In the 16 patients who had two echocardiographic studies, changes in the duration of isovolumic relaxation were accompanied by a change in the Doppler A/E ratio. The relation between these two variables, derived from the group as a whole was similar.
Conclusions—The main factors influencing the A/E ratio in patients with left ventricular disease are two distinct properties of isovolumic relaxation—namely the duration and the extent of incoordinate wall motion. Filling pressure and RR interval are not significant independent determinants, but act only through an effect upon isovolumic relaxation time. Age is an important influence in normal people, but this effect is attenuated in left ventricular hypertrophy and lost in ischaemic ventricular disease.
PMCID: PMC1025686  PMID: 1467050
7.  Echocardiographic indices in normal German shepherd dogs 
Journal of Veterinary Science  2006;7(2):193-198.
Sixty clinically normal German shepherd dogs, 31 males and 29 females, ranging in age from 1 and 5 years and with a body weight ranging from 22 to 37.2 kg, were examined by the two-dimensional mode, M-mode, and Doppler echocardiography. In Doppler mode, the mitral valve flows were obtained, where the aim was to determine the velocity peaks and ratios of the E and A waves and the mitral E wave deceleration time. The velocity peaks were obtained for the tricuspid, pulmonary and aortic valves. On the left ventricular outflow tract flow, the time velocity integral and aortic cross-sectional area was used to calculate the cardiac output. A statistically significant correlation with the body weight was found for the systolic left atrial and diastolic aortic diameter on two-dimensional mode. On M-mode, there was a significant correlation between the body weight and the systolic left atrium and diastolic aortic dimension, systolic and diastolic left ventricular, septal and posterior wall dimensions. Doppler echocardiography showed that there was no significant correlation between the body weight and the mitral, tricuspid, pulmonary and aortic valves flows. These results demonstrate that it is important to know the normal echocardiographic values for German shepherd dogs because there are some characteristics peculiar to this particular breed. The data obtained is expected to be helpful for studies on small animal cardiology.
doi:10.4142/jvs.2006.7.2.193
PMCID: PMC3242114  PMID: 16645347
Doppler echocardiography; echocardiography; M-mode; two-dimensional mode
8.  Comparison of acoustic quantification and Doppler echocardiography in assessment of left ventricular diastolic variables. 
British Heart Journal  1993;70(5):448-456.
OBJECTIVE--To assess the haemodynamic correlations of the waveforms of left ventricular area change obtained by automated boundary detection with newly developed acoustic quantification technology. DESIGN--The timing of events in the cardiac cycle was identified on the wave-form automated boundary detection and was correlated with the corresponding timing derived from pulsed wave Doppler flow velocity traces of the mitral valve and left ventricular outflow tract. The amounts of area change during the rapid filling phase and during atrial contraction were correlated with the time-velocity integrals of early and late diastolic ventricular filling obtained from Doppler tracings of the mitral inflow. SETTING--A university medical school echocardiography laboratory. SUBJECTS--16 healthy volunteers and 19 patients referred for echocardiographic studies. RESULTS--A significant correlation was found between the methods for measurement of the time from the R wave to mitral valve opening (r = 0.72, p < 0.01), isovolumic relaxation time (r = 0.62, p < 0.01), and ejection time (r = 0.54, p < 0.01). The change of total area that occurred during rapid filling and atrial filling phases measured from the acoustic waveform correlated with the time-velocity integrals of the early and late diastolic mitral valve inflow velocity derived from Doppler echocardiography (r = 0.60 and r = 0.80, respectively). CONCLUSION--The waveform of left ventricular area obtained by the automated boundary detection technique identifies the phases of the cardiac cycle and correlates with Doppler values of left ventricular diastolic function. Therefore, this new method of automated boundary detection has potential uses in the assessment of left ventricular diastolic function.
Images
PMCID: PMC1025358  PMID: 8260277
9.  Atrioventricular Flow Wave Patterns before and after Birth by Fetal Echocardiography 
Background
Doppler echocardiographic measurements of both valves during intrauterine life can be used to calculate peak early filling velocity (E)/late peak atrial filling velocity (A) ratio as a single index of diastolic performance. The purposes of this study were to estimate the changes in atrioventricular valve flow from gestational age 37-40 weeks to 1 month of postnatal life and to clarify the difference in right and left ventricular diastolic filling patterns.
Methods
Atrioventricular flow waves were analyzed in 24 full-term pregnant women by fetal echocardiography. Postnatal follow-up studies were performed at 1 hour, 6 hours, 24 hours, 3 days, 1 week and 1 month. In each time point, pulsed Doppler echocardiography was used to interrogate Doppler waveform of E velocity, A velocity, total area under the curve (time velocity integral) and heart rate.
Results
Mitral E/A ratio significantly increased from 0.7 ± 0.1 before birth to 1.0 ± 0.3 at postnatal 1 hour, 1.0 ± 0.2 at 1 week, and 1.5 ± 1.0 at 1 month. Tricuspid flow E/A ratio was 0.8 ± 0.3 before birth, 0.8 ± 0.1 at 1 hour, 0.8 ± 0.2 at 3 days, 0.9 ± 1.0 at 1 month. Time velocity integral of tricuspid flow was significantly higher than that of mitral flow before birth, but there was no difference after birth.
Conclusion
The dominance of mitral A wave before birth was changed very quickly after birth to the dominance of E wave, but the dominance of tricuspid A wave was maintained at 1 month. Diastolic function and compliance of mitral valve were better than those of the tricuspid valve after birth.
doi:10.4250/jcu.2012.20.2.85
PMCID: PMC3391633  PMID: 22787525
Fetal echocardiography; Atrioventricular valve flow
10.  Estimation of maximum intraventricular pressure: a three-dimensional fluid–structure interaction model 
Background
The aim of this study was to propose a method to estimate the maximum pressure in the left ventricle (MPLV) for a healthy subject, based on cardiac outputs measured by echo-Doppler (non-invasive) and catheterization (invasive) techniques at rest and during exercise.
Methods
Blood flow through aortic valve was measured by Doppler flow echocardiography. Aortic valve geometry was calculated by echocardiographic imaging. A Fluid–structure Interaction (FSI) simulation was performed, using an Arbitrary Lagrangian–Eulerian (ALE) mesh. Boundary conditions were defined as pressure loads on ventricular and aortic sides during ejection phase. The FSI simulation was used to determine a numerical relationship between the cardiac output to aortic diastolic and left ventricular pressures. This relationship enabled the prediction of pressure loads from cardiac outputs measured by invasive and non-invasive clinical methods.
Results
Ventricular systolic pressure peak was calculated from cardiac output of Doppler, Fick oximetric and Thermodilution methods leading to a 22%, 18% and 24% increment throughout exercise, respectively. The mean gradients obtained from curves of ventricular systolic pressure based on Doppler, Fick oximetric and Thermodilution methods were 0.48, 0.41 and 0.56 mmHg/heart rate, respectively. Predicted Fick-MPLV differed by 4.7%, Thermodilution-MPLV by 30% and Doppler-MPLV by 12%, when compared to clinical reports.
Conclusions
Preliminary results from one subject show results that are in the range of literature values. The method needs to be validated by further testing, including independent measurements of intraventricular pressure. Since flow depends on the pressure loads, measuring more accurate intraventricular pressures helps to understand the cardiac flow dynamics for better clinical diagnosis. Furthermore, the method is non-invasive, safe, cheap and more practical. As clinical Fick-measured values have been known to be more accurate, our Fick-based prediction could be the most applicable.
doi:10.1186/1475-925X-12-122
PMCID: PMC4222736  PMID: 24267976
11.  Non-invasive detection of left atrial mechanical failure in patients with left ventricular disease. 
British Heart Journal  1995;74(5):536-540.
OBJECTIVE--To define patients with left atrial mechanical failure and identify its echocardiographic, physiological, and clinical associations. DESIGN--Prospective study with cross sectionally guided M mode and Doppler echocardiograms, and with apexcardiograms, electrocardiograms, and phonocardiograms. SETTING--Tertiary cardiac referral centre. PATIENTS--10 patients with left atrial mechanical failure and 20 healthy controls of similar age. RESULTS--10 patients with left atrial mechanical paralysis were identified among 4036 adults over a 1 year interval. Nine were in sinus rhythm and one had a DDD pacemaker. Left atrial mechanical activity was absent on M mode echocardiograms of the left sided atrioventricular ring and the aortic root. A Doppler A wave on transmitral flow and a clearly defined A wave on the left ventricular apexcardiogram were also absent, though evidence of right atrial mechanical movement was present in nine patients. Mean (SD) age was 63 (19) years and six were men. Nine had left ventricular disease and one had undergone extensive resection of the left atrium. Abnormal measurements of left ventricular end diastolic dimension (62 (13) mm), fractional shortening (15 (6)%), isovolumic relaxation time (19 (12) ms), left atrial size (45 (10) mm), and transmitral Doppler E wave deceleration time (110 (35) ms) were recorded. CONCLUSION--Left atrial mechanical failure may be present in patients with left ventricular disease despite normal sinus rhythm. Normal atrial activation on 12 lead electrocardiogram suggests it is primarily mechanical in origin. The possibility of left atrial mechanical failure must be considered when Doppler patterns of transmitral flow are used to assess left ventricular diastolic function.
Images
PMCID: PMC484076  PMID: 8562241
12.  Reference ranges for cardiac dimensions and blood flow velocity in preterm infants 
Heart  1998;80(3):281-285.
Aim—To establish reference ranges for cardiac dimensions and Doppler measurements in preterm infants.
Methods—79 infants of less than 34 weeks' gestation were examined by echocardiography on days 0, 7, and 28 after birth, to produce a set of reference ranges and to examine changes in these indices over the first month of life. The following dimensions were measured: interventricular septum, left ventricular posterior wall, left interventricular diameter at end systole and diastole, left atrium, and aortic root; Doppler measurements were made of maximum blood flow velocity (Vmax) through the pulmonary, aortic, mitral, and tricuspid valves.
Results—Reference ranges are given. Cardiac dimensions correlated well with gestation and birth weight but Vmax did not. There was a significant increase in measurements over time. The "normal" preterm infant also appeared to often have asymmetrical septal hypertrophy. Antenatal dexamethasone administration did not appear to affect the measurements. 
Conclusions—There is a close correlation with both gestation and birth weight for all physical measurements. Echocardiograms in preterm babies clearly differ from those in older children and adults.

 Keywords: cardiac dimensions;  blood flow velocity;  preterm infant
PMCID: PMC1761096  PMID: 9875089
13.  Feasibility and variability of six methods for the echocardiographic and Doppler determination of cardiac output. 
British Heart Journal  1988;59(3):299-303.
The feasibility and the intrinsic variability of six different methods of echocardiographic and Doppler flow determination of cardiac output were analysed in 34 healthy volunteers. Four were excluded because of poor quality echocardiograms. The mean (range) age of the remaining 30 (12 women, 18 men) was 21 years (13-36 years). Cardiac output was calculated by six methods as a product of echocardiographically determined cross sectional area of the aorta (apical and suprasternal views), pulmonary trunk, tricuspid annulus, and mitral annulus (circular and corrected for diastolic variations), and the flow velocity integral measured by Doppler. Cardiac output ranged from 2.79 to 6.56 1/min (4.45 (1.29) 1/min) (mean (SD)). The feasibility of the methods ranged from 87% (26 patients) for the aorta from the suprasternal notch to 100% (30 patients) for the mitral orifice corrected for diastolic variations and for the tricuspid valve. The corresponding results for all 34 individuals were 76% and 88% respectively. Three way analysis of variance was performed in the 23 healthy volunteers in whom all six methods were feasible. Interobserver and intraobserver interpretative variabilities were 6.8% and 5.9% respectively. The intrinsic variability of each single measurement of cardiac output, independently of the observer and the method used, was 25%. Provided the image was suitable for analysis echocardiographic and Doppler flow determination of cardiac output was feasible in most healthy volunteers. But there was significant intrinsic variability for each of different methods. A single value of cardiac output in an individual should be interpreted with caution.
PMCID: PMC1216463  PMID: 3355721
14.  Pericardial effusion after cardiac surgery: incidence, site, size, and haemodynamic consequences. 
British Heart Journal  1994;72(4):327-331.
OBJECTIVE--To evaluate the incidence, characteristics, and haemodynamic consequences of pericardial effusion after cardiac surgery. DESIGN--Clinical, echocardiographic, and Doppler evaluations before and 8 days after cardiac surgery; with echocardiographic and Doppler follow up of patients with moderate or large pericardial effusion after operation. SETTING--Patients undergoing cardiac surgery at a tertiary centre. PATIENTS--803 consecutive patients who had coronary artery bypass grafting (430), valve replacement (330), and other types of surgery (43). 23 were excluded because of early reoperation. MAIN OUTCOME MEASURES--Size and site of pericardial effusion evaluated by cross sectional echocardiography and signs of cardiac tamponade detected by ultrasound (right atrial and ventricular diastolic collapse, left ventricular diastolic collapse, distension of the inferior vena cava), and Doppler echocardiography (inspiratory decrease of aortic and mitral flow velocities). RESULTS--Pericardial effusion was detected in 498 (64%) of 780 patients and was more often associated with coronary artery bypass grafting than with valve replacement or other types of surgery; it was small in 68.4%, moderate in 29.8%, and large in 1.6%. Loculated effusions (57.8%) were more frequent than diffuse ones (42.2%). The size and site of effusion were related to the type of surgery. None of the small pericardial effusions increased in size; the amount of fluid decreased within a month in most patients with moderate effusion and in a few (7 patients) developed into a large effusion and cardiac tamponade. 15 individuals (1.9%) had cardiac tamponade; this event was significantly more common after valve replacement (12 patients) than after coronary artery bypass grafting (2 patients) or other types of surgery (1 patient after pulmonary embolectomy). In patients with cardiac tamponade aortic and mitral flow velocities invariably decreased during inspiration; the echocardiographic signs were less reliable. CONCLUSIONS--Pericardial effusion after cardiac surgery is common and its size and site are related to the type of surgery. Cardiac tamponade is rare and is more common in patients receiving oral anticoagulants. Echo-Doppler imaging is useful for the evaluation of pericardial fluid accumulations after cardiac surgery. It can identify effusions that herald cardiac tamponade.
PMCID: PMC1025541  PMID: 7833189
15.  Portable spectral Doppler echocardiographic device: overcoming limitations 
Heart  2003;89(9):1014-1018.
Background: There is evidence that new portable echocardiographic devices are useful in evaluating heart anatomy and function, but a lack of Doppler modes has up to now been an important limitation in obtaining haemodynamic data.
Objectives: To report the Doppler capabilities of a new hand held echocardiographic device.
Design: Blinded comparison of two types of echocardiography machine.
Setting: Tertiary care centre.
Patients: 98 consecutive patients were randomly imaged with the hand held device, with a standard platform as reference.
Outcome measures: Pulsed wave transmitral Doppler inflow tract velocities, deceleration time, and continuous wave Doppler measurements of aortic ejection and tricuspid regurgitation peak velocities were recorded.
Results: There was excellent agreement between the hand held device and standard echocardiography for the evaluation of diastolic E and A waves, E/A ratio, and deceleration time with pulsed wave Doppler (intraclass correlation coefficients of 0.97, 0.93, 0.90, and 0.78, respectively). In addition, good agreement was found between continuous wave Doppler measurements of aortic ejection and tricuspid regurgitation velocities (intraclass correlation coefficients of 0.96 and 0.80). However, there was a significant difference between patients with tricuspid regurgitation measured with the hand held device (25.5%) and by standard echocardiography (65.3%), resulting in misdiagnosis of eight patients with pronounced pulmonary hypertension.
Conclusions: New hand held devices with Doppler capabilities overcome previous limitations in evaluating haemodynamic variables. With colour Doppler they are now suitable for the complete evaluation of valvar disease and diastolic function. However, important limitations remain in the evaluation of pulmonary pressures.
PMCID: PMC1767834  PMID: 12923013
echocardiography; Doppler; point of care system
16.  Sustained cardiac diastolic changes elicited by ultrafiltration in patients with moderate congestive heart failure: pathophysiological correlates. 
British Heart Journal  1993;70(2):135-140.
OBJECTIVE--To investigate the pathophysiological (cardiac function and physical performance) significance of clinically silent interstitial lung water accumulation in patients with moderate heart failure; to use isolated ultrafiltration as a means of extravascular fluid reabsorption. DESIGN--Echocardiographic, Doppler, chest x-ray evaluations, and cardiopulmonary tests at baseline, soon after ultrafiltration (veno venous extracorporeal circuit), and four days, one month, and three months later. SETTING--University institute of cardiology. SUBJECTS--24 patients with heart failure due to idiopathic dilated cardiomyopathy or ischaemic myocardial disease with sinus rhythm and ejection fraction less than 35%. Twelve were randomised to ultrafiltration and 12 were taken as controls. MAIN OUTCOME MEASURES--Left ventricular systolic function (from ultrasonography); Doppler evaluation of mitral, tricuspid, and aortic flow and echo-Doppler determination of cardiac output; radiological score of extravascular lung water; right and left ventricular filling pressures; oxygen consumption at peak exercise and exercise tolerance time in cardiopulmonary tests. RESULTS--Soon after ultrafiltration (1976 (760) ml of fluid removed) the following was observed: a reduction in radiological score of extravascular lung water (from 15(1) to 9(1)) and of right (from 7.1 (2.3) to 2.3 (1.7) mm Hg) and left (from 17.6 (8.8) to 9.5 (6.4) mm Hg) ventricular filling pressures; an increase in oxygen consumption at peak exercise (from 15.8 (3.3) to 17.6 (2) ml/min/kg) and of tolerance time (from 444 (138) to 508 (134) s); a slight decrease in atrial and ventricular dimensions; no changes in the systolic function of the left ventricle; a reduction of the early to late filling ratio in both ventricles (mitral valve from 2 (2) to 1.1 (1.1)); (tricuspid valve from 1.3 (1.3) to 0.69 (0.18)) and an increase in the deceleration time of mitral and tricuspid flow, reflecting a redistribution of filling to late diastole. Variations in the ventricular filling pattern, lung water content, and functional performance persisted for three months in all cases. None of these changes was detected in the control group. CONCLUSIONS--Reduction of interstitial lung water was probably the mechanism whereby ultrafiltration modified the pattern of filling of the two ventricles and improved functional performance.
PMCID: PMC1025273  PMID: 8038023
17.  New applications of intracardiac echocardiography: assessment of coronary blood flow by colour and pulsed Doppler imaging in dogs 
Heart  2002;88(3):283-288.
Objective: To explore the application of a new 10 French intracardiac echocardiography (ICE) catheter with phased array and Doppler capable transducer for the assessment of epicardial and intramyocardial coronary blood flow.
Methods: The coronary arteries were detected by cross sectional imaging in seven closed chest dogs, and coronary blood flow visualised by colour Doppler. Blood flow velocities were recorded by pulsed Doppler at baseline for reproducibility of repeated measurements, and during hyperaemia for coronary flow reserve measurements. Comparisons were made with Doppler guide wire data obtained simultaneously. Intramyocardial coronary artery blood flow was assessed by colour flow mapping, and the blood flow velocities recorded using pulsed Doppler at baseline and during hyperaemia.
Results: Seven left main, six left anterior descending, seven left circumflex, and five right coronary arteries were visualised in the seven animals by cross sectional or colour Doppler imaging. Repeated measurements of coronary flow velocity showed a good correlation (mean diastolic velocity, r = 0.93, n = 22, p < 0.0001; peak diastolic velocity, r = 0.96, n = 22, p < 0.0001, respectively). Intraobserver/interobserver variability was satisfactorily low. Coronary flow reserve from ICE correlated highly with the value obtained from the Doppler guide wire (r = 0.90, n = 26, p < 0.0001). Intramyocardial coronary blood flow was identified in all seven dogs, and flow velocities were recorded at baseline and during hyperaemia in four animals.
Conclusions: This new ICE catheter provides high quality diagnostic resolution. It is useful for coronary blood flow assessment.
PMCID: PMC1767320  PMID: 12181224
intracardiac echocardiography; Doppler echocardiography; coronary circulation
18.  Echocardiographic evaluation of thalassemia intermedia patients in Duhok, Iraq 
Background
Cardiac complications are among the most serious problems of thalassemia intermedia patients. The current study was initiated to address the latter issue through the study of the echocardiographic findings and correlate it with clinical characteristics of thalassemia intermedia patients in Duhok, Kurdistan region, Iraq.
Methods
An echocardiographic assessment of 61beta-thalassemia intermedia cases was performed. It included 30 males and 31 females, with a mean age 19.6 ± 7.5 years. The standard echostudy of two-dimension and M-mode measurements of cardiac chambers were done. The continuous doppler regurgitant jet of tricuspid and pulmonary valves were recorded. Left ventricle diastolic function was assessed by pulsed doppler of mitral valve inflow. To correlate the clinical with echocardiographic findings, patients were divided, according to tricuspid regurgitant velocity, into three groups (<2.5 m/sec, 2.5-2.9 m/sec and ≥3 m/sec).
Results
Tricuspid regurgitant velocity <2.5 m/sec, 2.5-2.9 m/sec and ≥3 m/sec occurred in 42(69%), 11(18%) and 8(13%) respectively. Comparing to other groups patients with tricuspid regurgitant velocity ≥3 m/sec were older and included more males. They had lower hemoglobin levels, but higher ferritin levels. Their age at diagnosis and the age of the initiation of blood transfusion were later. Most of them had significant exertional dyspnea. They also had relatively lower left ventricle ejection fraction values. Right ventricular diameter and right atrial size were larger in the same group. Tricuspid regurgitant velocity as a continuous predictor was associated positively with age, cardiac volumes and pulmonary regurgitation though negatively associated with ejection fraction.
Conclusions
Echo-derived right and left side cardiac complications are not uncommon in thalassemia intermedia patients. Therapeutic trails targeting these complications are indicated, and echocardiographic assessment is necessary to be offered early for thalassemia intermedia.
doi:10.1186/1471-2261-14-183
PMCID: PMC4272797  PMID: 25495194
Thalassemia intermedia; Tricuspid velocity jet; Pulmonary hypertension; Iraq
19.  Doppler Tissue Imaging: A Non-Invasive Technique for Estimation of Left Ventricular End Diastolic Pressure in Severe Mitral Regurgitation 
Background:
Conventional Doppler measurements, including mitral inflow and pulmonary venous flow, are used to estimate left ventricular end diastolic pressure (LVEDP). However, these parameters have limitations in predicting LVEDP among patients with mitral regurgitation. This study sought to establish whether the correlation between measurements derived from tissue Doppler echocardiography and LVEDP remains valid in the setting of severe mitral regurgitation.
Methods:
Thirty patients (mean age: 57.37 ± 13.29 years) with severe mitral regurgitation and a mean left ventricular ejection fraction (EF) of 46.0 ± 14.95 were enrolled; 16 (53.4%) patients were defined to have EF < 50% and 14 (46.6%) patients had EF ≥ 50%. Doppler signals from the mitral inflow, pulmonary venous flow, and Doppler tissue imaging indices were obtained, and LVEDP was measured invasively through cardiac catheterization.
Results:
The majority of the standard Doppler and Doppler tissue imaging indices were not significantly correlated with LVEDP in the univariate analysis. In the multiple linear regression, however, early (E) transmitral velocity to annular E′ (E/E′) ratio (β = 1.09, p value < 0.01), E wave velocity to propagation velocity (E/Vp) ratio (β = 7.87, p value < 0.01), and isovolumic relaxation time (β = 0.21, p value = 0.01) were shown as independent predictors of LVEDP (R2 = 91.7%).
Conclusion:
The ratio of E/Vp and E/E′ ratio and also the isovolumic relaxation time could be applied properly to estimate LVEDP in mitral regurgitation patients even in the setting of severe mitral regurgitation.
PMCID: PMC3466836  PMID: 23074579
Echocardiography, Doppler; Mitral valve insufficiency; Heart ventricles
20.  A Novel Approach to Standard Techniques in the Assessment and Quantification of the Interventricular Systolic Relationship 
Background
Blood flow between the right and left ventricles is subject to the continuity equation and systolic ventricular interdependence. Quantification of this relationship might aid in understanding inter-ventricular function. The purpose of this study was to evaluate and quantify ventricular interdependence by directly comparing right and left ventricular systolic function though echocardiographic surrogates of right and left ventricular systolic function such as MAPSE, TAPSE, RV TVI and LV TVI.
Methods
This study prospectively evaluated 51 healthy participants (mean age, 41 ± 17 years) by resting echocardiography. In addition to standard measurements, tricuspid annular plane of systolic excursion, (TAPSE), mitral annular plane of systolic excursion (MAPSE), and the peak annulus systolic velocity of the right ventricular (RVs) and left ventricular (LVs) free walls were measured by M-mode and pulsed wave Doppler tissue echocardiography and further evaluated for variance across age, gender, and body surface area.
Results
TAPSE (22.1 ± 2.9 mm) was over 54.5% greater than MAPSE (14.3 ± 2.6 mm) and RVs was 64.4% greater than LVs. The LV to RV systolic relationship measured by MAPSE/TAPSE and LVs/RVs ratios were 0.66 ± 0.14 and 0.76 ± 0.21 respectively. These values were not significantly affected by age, gender or body surface area (BSA).
Conclusion
MAPSE/TAPSE and LVs/RVs ratios appear stable across age, gender, and BSA potentially making them good surrogates of systolic ventricular relationship and interdependence.
doi:10.1186/1476-7120-9-42
PMCID: PMC3280943  PMID: 22185470
ventricular interdependence; ventricular function; TAPSE; MAPSE; tissue Doppler
21.  Doppler echocardiographic evaluation of the normal human fetal heart. 
British Heart Journal  1987;57(6):528-533.
Pulsed wave Doppler estimates of blood flow velocity were made across the mitral, tricuspid, aortic, and pulmonary valves in a series of 120 normal fetuses (gestational age 16-36 weeks). In 36 of these the data were obtained in all four sites. The maximum and mean velocities were calculated for each valve and these values were plotted against gestational age. There was little change in these values throughout pregnancy. The orifice dimensions of the valves were measured by cross sectional echocardiography. At all ages the tricuspid orifice was larger than the mitral and the pulmonary orifice was larger than the aortic. The blood flow values for each valve were derived from the product of the mean velocity and the valve orifice dimensions. The output of the right ventricle was usually, but not always, greater than that of the left ventricle. Combined ventricular output increased from approximately 50 ml/min at 18 weeks to 1200 ml/min at term. Despite limitations in the accuracy of the technique these results form a useful basis for the analysis of blood flow in the normal fetus and for the interpretation of abnormal Doppler findings in prenatal life.
Images
PMCID: PMC1277222  PMID: 3620229
22.  Reliability of quantitative echocardiography in adult sheep and goats 
Background
Echocardiography is a non-invasive method for assessment of the ovine and caprine heart. Complete reference ranges for cardiac dimensions and time indices for both species are not currently available and reliability of these measurements has not been evaluated. The objectives for this study are to report reliability, normal cardiac dimensions and time indices in a large group of adult sheep and goats.
Fifty-one adult sheep and forty adult goats were recruited. Full echocardiographic examinations were performed in the standing unsedated animal. All animals underwent echocardiography four times in a 72-hour period. Echocardiography was performed three times by one author and once by another. Images were stored and measured offline. Technique and measurement repeatability and reproducibility and any differences due to animal or day were evaluated. Reference ranges (mean ± 2 standard deviations) were calculated for both species.
Results
Majority of the images obtained were of good to excellent quality. Image acquisition was straightforward with 5.4% of animals demonstrating a small scanning window. Reliability was excellent for majority of dimensions and time indices. There was less variation in repeatability when compared with reproducibility and differences were greater for technique than for measurements. Dimensions that were less reliable included those for right ventricular diameter and left ventricular free wall. There were many differences in cardiac dimensions between sheep and goats.
Conclusions
This study has demonstrated that specific reference ranges are required for these two species. Repeatability and reproducibility were excellent for the majority of cardiac dimensions and time indices suggesting that this technique is reliable and valuable for examination of clinical cases over time and for longitudinal research studies.
doi:10.1186/1746-6148-8-181
PMCID: PMC3574009  PMID: 23017011
Ovine; Caprine; Cardiac; Heart; Measurements; Ultrasonography
23.  Acute effects of cigarette smoking on the cardiac diastolic functions 
Background
Smoking is an independent risk factor for coronary heart diseases and it increases all causes of cardiovascular morbidity and mortality.
Aim of the work
To assess the acute effect of cigarette smoking on ventricular diastolic functions (LV and RV) in healthy, young, and slim smokers.
Methods
Thirty volunteers who had recently commenced smoking (less than one year) and who smoked 1–2 cigarettes per day, underwent ECG, 2D and M-mode echocardiography, standard Doppler echocardiography, pulsed TDI (tissue Doppler imaging) on septal and lateral side of mitral annulus and lateral tricuspid annulus. Vp values were measured. The investigator asked them to hold smoking for at least two days after which echocardiographic examination was conducted before smoking one cigarette and the second examination conducted immediately after smoking one cigarette containing at least 0.4 mg of nicotine.
Results
Doppler findings over the mitral valve showed the E wave was significantly reduced from 82.7 ± 10.4 to 74.6 ± 10.4 after smoking; the A wave increased; the E/A ratio was reduced from 1.5 ± 0.3 to 1.2 ± 0.2; the E′ septal significantly decreased (15.3 ± 2.4 vs. 11.2 ± 1.1) after smoking, and the E/E′ ratio increased from 5.5 ± 1.1 to 6.7 ± 1.1. Doppler findings over the tricuspid valve showed the E wave was reduced from 60.6 ± 9.7 to 52.7 ± 9.6; the A wave increased from 42.2 ± 6.5 to 50.1 ± 6.6; and the E/A ratio decreased (1.45 ± 0.25 vs. 1.06 ± 0.19). The E′ significantly decreased from 14.1 ± 1.8 to 10.9 ± 2.4, while the A′ increased (10.2 ± 2.4 vs. 12.7 ± 3.6) after smoking; and the IVRT of the RV was significantly prolonged from 62.9 ± 7.5 to 68.7 ± 7.9 after smoking. The Vp was markedly reduced from 67.8 ± 8 to 55.2 ± 3.5 after smoking. These findings reflected on the LV filling pressure (LVFvp) which increased from 9.8 ± 1.4 to 10.5 ± 1.3 after smoking. All changes were statistically significant at P < 0.001.
Conclusions
Our study reveals that cigarette smoking can result in significant acute alteration in the diastolic functions of both ventricles.
doi:10.1016/j.jsha.2013.03.003
PMCID: PMC3809467  PMID: 24174857
Cigarette; Smoking; RV dysfunction; LV dysfunction; Acute effect
24.  Discrepancies in the measurement of isovolumic relaxation time: a study comparing M mode and Doppler echocardiography. 
British Heart Journal  1990;64(3):214-218.
Mitral valve cusp separation on M mode echogram, the mitral valve opening artefact, and the onset of forward transmitral flow recorded by Doppler echocardiography have all been taken to mark the end of isovolumic relaxation, while its onset has been taken either as the aortic closure sound (A2) recorded phonocardiographically or the aortic closure artefact determined by Doppler technique. Possible differences in the measurement of the isovolumic relaxation time were studied when these landmarks were used in 44 healthy people, 14 patients with mitral stenosis, 21 patients with left ventricular hypertrophy, and 24 patients with dilated cardiomyopathy by recording M mode echograms of the mitral valve, and pulsed and continuous wave Doppler spectra of transmitral flow, with simultaneous electrocardiograms and phonocardiograms. A2 was effectively synchronous with the aortic artefact. However, when the onset of Doppler flow was regarded as the end of isovolumic relaxation, the interval was significantly longer than when mitral cusp separation on M mode echograms was used: by 25 (10) ms in healthy individuals, by 25 (15) ms in patients with left ventricular hypertrophy, and by 50 (35) ms in patients with dilated cardiomyopathy. In patients with mitral stenosis the interval was only 5 (5) ms longer. The mitral valve opening artefact consistently followed the onset of flow and corresponded much more closely to the E point on the M mode echogram. This shows that it occurred during the rapid filling period and well beyond isovolumic relaxation by any definition. Thus isovolumic relaxation time measured from A2 to the onset of transmitral flow or the mitral valve opening artefact differs from that derived from A2 to mitral valve cusp separation. These intervals cannot be used interchangeably to measure "isovolumic relaxation time".
PMCID: PMC1024377  PMID: 2144990
25.  Thyroid Function Status and Echocardiographic Abnormalities in Patients with Beta Thalassemia Major in Bahrain 
Background:
Thyroid gland dysfunction and echocardiographic cardiac abnormalities are well-documented in patients with transfusion dependent beta-thalassemia major (β-TM).
Aim:
This cross-sectional analytic study was conducted to investigate left ventricle (LV) diastolic and systolic function using pulsed Doppler (PD) and tissue Doppler (TD) echocardiography and correlate that with serum level thyroid stimulating hormone in patients with β-TM.
Methods:
The study was conducted on patients with β-TM (n = 110, age 15.9 ± 8.9 years) and compared with a control group (n = 109, age 15.8 ± 8.9 years). In all participants, echocardiographic indices of PD and TD were performed and blood samples were withdrawn for measuring the serum level of TSH, free T4, and ferritin. A linear regression analysis was performed on TSH level as the dependent variable and serum ferritin as independent. Stepwise multiple regression analysis was used to determine the odds ratio of different biochemical and echo variables on the risk of developing hypothyroidism.
Results:
Patients with β-TM compared with controls had thicker LV septal wall index (0.65 ± 0.26 vs. 0.44 ± 0.21 cm/M2, P < 0.001), posterior wall index (0.65 ± 0.23 vs. 0.43 ± 0.21 cm/m2, P < 0.01) and larger LVEDD index (4.35 ± 0.69 vs.3.88 ± 0.153 mm/m2, P < 0.001). In addition, β-TM patients had higher transmitral E wave velocity (E) (70.81 ± 10.13 vs. 57.53 ± 10.13 cm/s, P = 0.02) and E/A ratio (1.54 ± 0.18 vs. 1.23 ± 0.17, P < 0.01) and shorter deceleration time (DT) (170.53 ± 13.3 vs. 210.50 ± 19.20 m sec, P < 0.01). Furthermore, the ratio of transmitral E wave velocity to the tissue Doppler E wave at the basal septal mitral annulus (E/Em) was significantly higher in the β-TM group (19.68 ± 2.81 vs. 13.86 ± 1.41, P < 0.05). The tissue Doppler systolic wave (Sm) velocity and the early diastolic wave (Em) were significantly lower in the β-TM group compared with controls with Sm, 4.82 ± 1.2 vs. 6.22 ± 2.1 mm/sec, P < 0.05 and (Em), 3.51 ± 2.7 vs. 4.12 ± 2.5 mm/sec. P < 0.05, respectively). The tricuspid valve velocity was significantly higher in β-TM patients compared with controls 2.85 ± 0.56 vs. 1.743 ± 0.47 m sec, respectively, P < 0.01). The prevalence of subclinical hypothyroidism in patients with β-TM was 15.4%, with significantly higher mean serum TSH compared with controls (6.78 ± 1.5 vs. 3.10 ± 1.02 μIU/mL, P < 0.01) and positively correlated with the serum ferritin level (r = 0.34, P = 0.014). On multiple regression analysis, the LV mass, LVEF%, and E/A ratio were not positive predictors of hypothyroidism in patients with β-TM.
Conclusion:
We conclude that patients with β-TM had a high prevalence of subclinical hypothyroidism of 15.4%. Thyroid stimulating hormone was significantly high and positively correlated with the serum ferritin level. Echo cardiographic pulsed Doppler showed a restrictive LV diastolic pattern suggestive of severe diastolic dysfunction with preserved left ventricle systolic function.
doi:10.4137/CMC.S10702
PMCID: PMC3563303  PMID: 23400522
thyroid stimulating hormone; beta-thalassemia major; pulsed echo Doppler; tissue Doppler echocardiography; Bahrain

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