Isovolumetric acceleration (IVA) is a novel tissue Doppler parameter for the assessment of systolic function. The aim of this study was to evaluate IVA as an early parameter for the detection of right ventricular (RV) systolic dysfunction in patients with systemic sclerosis (SSc) without pulmonary hypertension.22 patients and 22 gender- and age-matched healthy subjects underwent standard echocardiography with tissue Doppler imaging (TDI) and speckle tracking strain to assess RV function.2 vs. 4.1 ± 0.8 m/s2, p < 0.001) were significant lower in the patient group. IVA was the best parameter to predict early systolic dysfunction with an area under the curve of 0.988.Tricuspid annular plane systolic excursion (TAPSE) , peak myocardial systolic velocity (Sm) , isovolumetric contraction velocity (IVV)  and IVA (2.3 ± 0.4 m/sIVA is a useful tool with high-predictive power to detect early right ventricular systolic impairment in patients with SSc and without pulmonary hypertension. Systemic sclerosis is a connective tissue disease characterized by vascular inflammation and fibrosis. Visceral involvement, e.g. pulmonary fibrosis, pulmonary hypertension, myocardial and renal affliction, is associated with poor prognosis -4. CardiPrimary myocardial involvement and pulmonary hypertension are common in SSc. According to histological and clinical studies, cardiac involvement occurs in up to 80% of SSc patients ,6-8. It Novel echocardiographic approaches like Tissue Doppler Imaging and Speckle Tracking Strain Imaging improved the assessment of myocardial systolic and diastolic function in both left and right ventricle and therefore led to better detection of subclinical cardiac involvement in patients with SSc ,12. PrevIsovolumetric acceleration (IVA) is a new tissue Doppler parameter for the assessment of systolic function of both left and right ventricle. IVA is calculated as the ratio of Tissue Doppler derived peak myocardial velocity during isovolumetric contraction (IVV) divided by the acceleration time (AT). This parameter has been validated in a variety of experimental and clinical settings. While IVA remains unaffected by changes in pre- and afterload within the physiological range, it can detect small changes in contractile function ,18. FirsThe aim of this study was to assess right ventricular diastolic and systolic function in patients with SSc without pulmonary hypertension and to evaluate IVA as an early parameter for the detection of systolic dysfunction in these patients.Twenty-two patients with SSc  were included into the study. According to serological antibody analysis and Rodnan Skin Score, 11 patients had a limited form and 11 patients suffered from a diffuse form of SSc. Serological antibody analysis revealed the presence of anti-centromere pattern in 8 patients, and anti Scl-70 in 9 patients. All patients presented with normal pulmonary artery pressure as determined by transtricuspid conventional Doppler echocardiography. Three patients with poor RV images were excluded from the study. For comparison, 22 gender-  and age-matched  subjects with a clinical indication for routine echocardiography and normal findings were used as control group. All participants provided written consent. The local ethics committee approved the protocol.In all patients, a pulmonary function test was performed  according to the recommendations of the American Thoracic Society prior to echocardiography .Standard echocardiography was performed in the left decubitus position using an ultrasound system  with a 3.4-MHz multifrequency transducer. RV images were obtained from the parasternal short axis and at the modified apical four-chamber view to optimize RV visualization. The two RV outflow tract diameters (RVOT1 and RVOT2) were measured in the two-dimensional parasternal short axis as recommended by the European Association of Echocardiography and American Society of Echocardiography . The RV 2) and the right atrial pressure derived by the diameter of the inferior vena cava and the collapsibility index [Tricuspid valve regurgitation was detected at the apical four-chamber view by colour Doppler echocardiography. Transtricuspid retrograde velocities were obtained using continuous-wave Doppler. Systolic pulmonary artery pressure was estimated from the peak pressure gradient calculated from three consecutive beats using the modified Bernoulli formula , peak myocardial systolic velocity (Sm), peak early and late diastolic velocities (Em and Am), isovolumetric contraction time (IVCT), isovolumetric relaxation time (IVRT) and ejection time (ET) were measured Figures .All images were stored digitally for offline analysis . B-Mode images of the RV free wall were used to measure 2D strain using speckle-tracking algorithm. 2D strain in the basal, mid and apical segment of the RV free wall was measured. For TDI analysis, 3 beats were stored. The region of interest (ROI) for TDI strain was placed at basal, mid and apical segment of the RV free wall. TDI strain in each segment was averaged over 3 consecutive cardiac cycles. The myocardial acceleration during isovolumetric contraction (IVA), defined as the ratio of IVV divided by the acceleration time , and the myocardial performance index or Tei index, defined as the ratio between total RV isovolumetric time (IVCT and IVRT) divided by ejection time (ET), were also calculated offline ,26. The Three echocardiographers, blinded to clinical data, independently measured IVV and AT and calculated IVA of 10 randomized subjects (five patients and five controls) for interobserver variability analysis. One observer calculated IVA twice for the 10 randomized subjects on two consecutive days for intraobserver variability analysis.Statistics were calculated by software . All results are presented as mean ± standard deviation (SD). The Mann-Whitney nonparametric test was used to compare echocardiographic data from patients and control subjects. Differences were considered statistically significant if the P value was less than 0.05. Receiver-operating characteristic curve analysis was performed to test the diagnostic accuracy for discrimination of patients from controls and to determine optimal cut off values. The correlation was calculated as Pearson's r coefficient to assess univariate relations. Interclass Correlation Coefficient by Kolmogorov-Smirnov was used to calculate inter- and interobserver variability.Age, gender, body mass index, systolic and diastolic blood pressure as well as the incidence of cardiovascular risk factors such as hypertension, hypercholesterolemia and diabetes mellitus did not differ significantly between patient and control group Table . The valLV ejection fraction was similar in both groups . There were no significant differences in RVOT1 , RVOT2 , RV diameter  and RVEF  between patients and control subjects. TAPSE as a parameter for RV systolic function measured in M-mode was significantly smaller in patients with SSc compared to the control subjects .In speckle tracking strain analysis, peak systolic strain values were significantly different between both groups in the basal and medial segments of the RV free lateral wall with higher values in the control group . However, there was no significant difference in the peak systolic strain in the apical segment . In six controls and three patients, basal and medial 2D-strain was not measurable due to poor tracking. Apical 2D-strain could not be evaluated in five controls and in two patients respectively. DTI-derived peak systolic strain analysis showed significant differences in all segments of the RV free lateral wall between the scleroderma and the control group. Only in one patient, DTI-derived strain in the medial segment could not be measured due to echo artefacts and reverberation [Table The parameters derived from pulsed wave myocardial TDI are listed in Table There are no significant differences among the echo parameters in patients with diffuse and limited type of SSc Table .2 had a sensitivity of 1.0 and a specificity of 0.91 to predict early systolic right ventricular dysfunction with a positive predictive value and negative predictive value of 1.0 and 0.92, respectively. The AUC for IVV was 0.861, the peak systolic myocardial velocity (Sm) had an AUC of 0.747 and TAPSE had an AUC of 0.742 [Figure Receiver operating characteristic curve analysis was performed to calculate the best cut-off value to predict early systolic and diastolic right ventricular dysfunction in patients with SSc and normal pulmonary arterial pressure. The best parameter to predict early systolic dysfunction was IVA with an area under the curve (AUC) of 0.988. An IVA value less than 3.0 m/s2 Linear = 0.013).There was no correlation between early-impaired RV systolic function determined by reduced IVA and the degree of impaired DLCO in the pulmonary function test (RInter- and intraobserver variability were found to be good for IVA with an intraclass correlation coefficient of 0.97 (CI 0.94-0.99), p < 0.0001 and 0.98 (CI 0.97-0.99), p < 0.0001.We could demonstrate that in patients with SSc without pulmonary hypertension systolic and diastolic RV function was impaired. These findings were independent from the subtype of disease.Only three patients could not be included in this study because of poor RV images. This indicates an acceptable feasibility of echocardiographic assessment of RV function in SSc patients.Tissue Doppler derived peak systolic velocities and strain as well as two dimensional strain and TAPSE are useful tools to determine early right ventricular systolic dysfunction in patients with SSc without Doppler signs of pulmonary arterial hypertension whereas right ventricular dimension and ejection fraction did not differ significantly from the control group. Even though TAPSE and peak systolic velocity (Sm) were significantly lower compared to the controls in this study, their respective values were still within the normal range according to previously published studies -31.Two-dimensional strain is a new Doppler independent approach for calculation of strain, strain rate, tissue velocity, and displacement. It is based on speckle tracking analysis in B-Mode and therefore angle independent . PreviouIVA is a new sensitive parameter for ventricular contractile function. This parameter has been evaluated in a variety of experimental and clinical settings ,19,34-362 predicted SSc patients with 100% sensitivity and 91% specificity.Our findings demonstrate that right ventricular IVA, derived by pulsed TDI at lateral tricuspid annulus, has the highest predictive power with the best AUC for detection of early systolic dysfunction. This parameter has a low inter- and intraobserver variability and may be used as an accurate, non-invasive parameter for assessment of RV systolic function in patients with SSc especially to detect early systolic disturbances. An IVA < 3.0 m/sMore than 85% of the patients in our study showed a reduced DLCO. A decreased DLCO is a good predictor for development of pulmonary hypertension in patients with SSc and may exist years before pulmonary hypertension is diagnosed . In a coRV function could be affected by an impaired left ventricular function. Hence, left ventricular function was analyzed in this patient population and control group as part of routine echocardiography and was found to be within normal and did not differ between the groups.Lindqvist et al. could demonstrate an impairment of RV diastolic function with an increase in RV wall thickness and RA area in patients with SSc and normal pulmonary artery pressure. Left ventricular function and right ventricular systolic function were not altered even though pulmonary artery acceleration time was reduced in the patient group . As LV fOur findings of diastolic RV dysfunction were comparable to the results published by Lindqvist et al. In contrast, we also found significantly reduced systolic right ventricular function as determined by reduced IVA. Systolic myocardial velocity (Sm) and TAPSE were also significantly lower compared to our controls but still in normal range according to previously published studies -31. Thernd decade of life, with a progressive decline of IVA in each following decade [The duration of IVA lies in the range of 20-40 msec. Therefore, even with high frame rate approaches like Tissue Doppler Imaging (130-250 fps), were data are acquired every 4-6 msec., low temporal resolution due to technical limitations might represent a relevant source of error. Like all Doppler measurements, IVA is angle dependent. In malpositioned hearts or transducers when the angle of Doppler signal cannot be aligned optimally significant differences may occur. Furthermore, IVA is age-dependent. The highest IVA will be found in the 2g decade . The ageThis study demonstrated an early RV systolic and diastolic dysfunction in patients with SSc without Doppler indices for pulmonary hypertension. IVA is a new TDI derived index of contractile function with high sensitivity and specificity. IVA is a useful tool with high-predictive power to detect early right ventricular systolic impairment in these patients. With a low intra- and interobserver variability this parameter is easy to measure and not influenced by loading conditions in the physiological range. In order to detect RV- systolic dysfunction as well as diastolic dysfunction in early stages of SSc, further multicenter studies with larger patient numbers are needed to evaluate this parameter for clinical practice.The authors declare that they have no competing interests.SS and FK equally contributed to the study. SS, FK, ACB, AG, IP, HD, participated in contributions to conception, analysis and interpretation of data. BG has supervised and commented the study. ACB was the supervisor of echo examinations, is head of the echo lab, and contributed by revising the manuscript critically. All authors read and approved the final manuscript.Control subject: 2D longitudinal strain of the right ventricle. Control subject: 2D longitudinal strain of the right ventricle. The values of the basal, mid and apical segment of the free lateral wall were taken for further analysis.Click here for fileSSc patient: 2D longitudinal strain of the right ventricle. SSc patient: 2D longitudinal strain of the right ventricle. The values of the basal, mid and apical segment of the free lateral wall were taken for further analysis.Click here for file


Three dimensional echocardiography (3DE) approaches the accuracy of cardiac magnetic resonance in measuring left ventricular (LV) volumes and ejection fraction (EF). The multibeat modality in comparison to single-beat (SB) requires breath-hold technique and regular heart rhythm which could limit the use of this technique in patients with atrial fibrillation (AF) due to stitching artifact. The study aimed to investigate whether SB full volume 3DE acquisition reduces inter- and intraobserver variability in assessment of LV volumes and EF in comparison to four-beat (4B) ECG-gated full volume 3DE recording in patients with AF.A total of 78 patients were included in this study. Fifty-five with sinus rhythm (group A) and 23 having AF (group B). 4B and SB 3DE was performed in all patients. LV volumes and EF was determined by these two modalities and inter- and intraobserver variability was analyzed.SB modality showed significantly lower inter- and intraobserver variability in group B in comparison to 4B when measuring LV volumes and EF, except for end-systolic volume (ESV) in intraobserver analysis. There were significant differences when calculating the LV volumes (p < 0.001) and EF (p < 0.05) with SB in comparison to 4B in group B.Single-beat three-dimensional full volume acquisition seems to be superior to four-beat ECG-gated acquisition in measuring left ventricular volumes and ejection fraction in patients having atrial fibrillation. The variability is significantly lower both for ejection fraction and left ventricular volumes. Accurate quantification of LV volumes and EF has important diagnostic, prognostic and therapeutic implications. The variety of therapeutic decisions should be on the basis of LV volume and EF measures in various patient groups . 2DE is The most commonly used 3DE method for volume and EF measurement is to use real-time ECG- gated volume stitching from four consecutive 4B with the purpose to maintain an acceptable spatial and temporal resolution . The recAssessment of LVEF during AF has conventionally proved difficult because of beat-to-beat variation -13. Due The study sought to investigate whether SB full volume 3DE acquisition reduces inter- and intraobserver variability when measuring LV volumes and EF in comparison to 4B ECG-gated full volume 3DE recording in patients with AF.We included fifty-five consecutive adult patients  having SR (67 ± 10 beats/sec) who were referred to the echocardiographic examinations on varying clinical reasons  equipped with M5S probe. All acquisitions were performed by the same experienced operator with the patients in the left lateral position. Data sets were stored digitally for off-line analysis using commercially available software .A novel 3V matrix-array transducer was used for acquiring the 3D images. Gain and compression controls, as well as time gain compensation settings were optimized to enhance image quality.A full volume scan was acquired from four consecutive cardiac cycles fig.  and 1 caTwo readers analyzed the 3D images twice blinded to all clinical data and previous reading. All measurements were made twice one week apart.diff × 100%)/total mean × √2 (Dahlberg's formula) [diff is the SD of difference between measurements. All variables were tested for normality using the Kolmogorov-Smirnov test. Different echocardiographic data were tested using paired t-tests. The significance level was set as p < 0.05. Statistical analysis was performed using standard statistical software .All data are expressed as mean ± SD. Bland and Altman analysis was performed to determine the systematic bias and limits of agreement of LV volumes and EF between the different methods . In ordeformula) , where SEchocardiographic analyses were successfully completed in seventy patients. Five patients in group A and three patients in group B were excluded from the study due to poor acoustic window or because clear endocardial border visualization was difficult (two segments or more). Average image time resolution for 4B was 72 ± 18 volumes per second, whereas for SB data sets were acquired at 21 ± 5 volumes per second.The mean EDV, ESV and EF in group A using 4B and SB is presented in table The mean EDV, ESV and EF by 4B and SB in group B are demonstrated in table The limits of agreement analysis of LV volumes and EF in group B by different methods are shown in table The total patient population both in group A and B were analyzed to determine interobserver reproducibility. Intra- and interobserver variability in group A and B using 4B and SB is presented in table There were no significant differences in heart rate during acquisition period by 4B and SB modality.To our knowledge, this is the first study comparing two 3DE techniques side-by-side, 4B and SB in AF. Currently, quantitative measurements of LV size and function are most commonly obtained using the biplane Simpson's rule  with 2D In this study, LV volumes and EF in group A were comparable in these two different acquisition techniques (4B and SB respectively) without any significant differences. This finding is not in concordance by a recent publication by Macron L et al. . The onlEF measurements in AF patients are challenging in clinically practice due to the need of measuring an average of heart beats . From a In group B we found significant differences in EDV, ESV and EF when comparing 4B vs. SB which was not surprising considering to beat-to-beat variation. The mean differences were rather poor, -32.5 ± 15 ml for EDV, -12.2 ± 10.5 ml for ESV and -7 ± 10% for EF between 4B and SB, especially considering that this patient population had normal LV volumes. Additionally, CI for the respective measurements was rather wide, 65 ml, 42 ml and 40% respectively. Again, this is expected in AF patients and this study was not addressed to investigate this issue. Furthermore, LV volumes and EF using 4B were significantly smaller in comparison to SB (p < 0.0001 for LV-volumes and p < 0.05 for EF). From clinical point of view, perhaps the most important finding in this study is the lower variability of SB in comparison to 4B when measuring LV volumes and EF in AF . One explanation might be that the software has difficulties in tracking the endocardial border in AF when gathering volume in 4B because of stitching artifacts due to the irregular heart rate fig. . The geoWe have only analyzed our data using the GE equipment/software and this is likely that the effect might depend upon the software and equipment being used.There are today three software packages from three different vendor's commercially available for the measurement of 3D data. These softwares work with different algorithm and are not automatically interchangeable. To avoid future problems with vendor's specific results this should be tested separately or ideally it would desirable to use same algorithms.We have not been able to measure the R-R interval in the each three-dimensional modality since this was not possible using the current software. A more robust test-retest variablity would perhaps been if the patients were rescanned and separate datasets acquired and analysed. This might be a true analysis of test-retest variability and would be more clinically relevant.SB modality is a relatively new 3DE technique which reduces intra- and interobserver variability in patients with irregular heart rhythm. SB leads to loss of stitching artifact and reduces the acquisition time. Therefore, when 3DE is used in clinical practice in AF patients, SB modality should be recommended before multi-beat technique.Single-beat three-dimensional full volume acquisition seems to be superior to four-beat ECG -gated acquisition in measuring LV volumes and EF in patients having atrial fibrillation. The variability is significantly lower both for EF and LV volumes. More studies are needed to confirm this before implementing single-beat in every day clinical practice.The authors declare that they have no competing interests.RW and KS introduced the study idea. KS acquired the ultrasound images. AA and KS performed the off-line analysis. AM helped in the interpretation of the results and statistical analysis. KS wrote the manuscript, RW and PG added clinical discussion to the manuscript. LÅB reviewed the manuscript. Finally, all authors read and approved the manuscript.


Morbidity and mortality rates are higher in patients with severe left ventricular (LV) systolic dysfunction and ECG-derived prolonged QRS interval than in those with normal QRS duration. QRS duration is currently used on the grounds that it reflects the presence of ventricular dyssynchrony. However, 30–40% of patients selected on the basis of a prolonged QRS do not receive benefit by cardiac resynchronization therapy (CRT) since they do not show any significant inverse LV remodeling and QRS duration does not accurately distinguish responders to CRT. Consequently, mechanical dyssynchrony (particularly intra-ventricular dyssynchrony) seems to be much more important than electrical dyssinchrony. Pre- and post-echocardiographic assessment should require the combination of conventional and specific applications ranging from M-mode and pulsed/continuous Doppler, to pulsed Tissue Doppler, the off-line analysis of colour Tissue Velocity Imaging, Strain Rate Imaging, and real time three-dimensional reconstruction However, there is not no consensus about the best approach and the best ultrasound parameter for selecting candidates to CRT and ECG representation of abnormal cardiac conduction still remains as the main criterion in guidelines. This review is a practical update of ultrasound methods and measurements of atrio-ventricular, inter-ventricular and intra-ventricular dyssynchrony and describes experiences which used either conventional Doppler echocardiography and more advanced techniques. By these experiences, the global amount of LV dyssynchrony seems to be critical: the greater intra-ventricular dyssynchrony, the higher the possibility of significant LV inverse remodeling. After CRT, it is necessary also to evaluate the optimal atrio-ventricular delay and ventricular-ventricular delay setting that maximizes LV systolic function. Bi-Ventricular Pacing (BIVP) and Cardiac Resynchronization Therapy (CRT) have become additional treatment aimed to synchronizing biventricular activation and contraction in patients with severe chronic heart failure (CHF) associated with interventricular conduction delay. CRT is effective in improving functional capacity and degree of secondary mitral regurgitation . Th. Thpost-patients , SRI indIt is important to point out that all colour Tissue Doppler derived techniques require high 2-D frames rates (>90 frames/s)  and thattime difference ≥ 130 ms between the radial strain peak of LV posterior wall and anterior septum has shown to be highly predictive of an improved EF during follow-up, with 89% sensitivity and 83% specificity [The 2-D strain (speckle tracking) technique has very recently been used to assess radial dyssynchrony before/after CRT. Speckle tracking has been applied to routine mid-ventricular short-axis images to calculate radial strain from multiple circumferential points averaged to six standard segments and dyssynchrony from timing of peak radial strain has been demonstrated to be correlated with Tissue Doppler measures in 47 subjects . A time cificity .Three-dimensional (3-D) echocardiography allows intra-ventricular dyssynchrony to be evaluated by analyzing LV wall motion in multiple apical planes during the same cardiac cycle. It also offers better spatial resolution than a single plane. The global LV volumetric dataset has been used to determine a dyssynchrony index that corresponds to the standard deviation of the average of the time intervals needed by multiple LV segments to reach minimal end-systolic volume  Figure . This insurface rendering" visualization of the extent of dyssynchrony. The method is fast (a few seconds) and easy to perform, but has a lower temporal resolution than 2-D TSI. Partial experiences from Badano et al [triplane Ts-SD  = 35.8 ms predicts an acute (48 hours after CRT) reverse LV remodeling with 91% sensitivity and 85% specificity [A new "real-time" 3D approach acquires three standard apical views during the same heart beating (Triplane). The images can also be acquired in TSI modality Figure , thus alno et al ,42 have cificity .On the grounds of the multiple mentioned experiences, the ultrasound examination of candidates for CRT requires specific measurements of mechanical dyssynchrony. This can be made by combining PW/CW Doppler and M-mode echocardiography (or PW Tissue Doppler or color Tissue Doppler derived techniques or 3-D imaging). Table Although several studies have demonstrated the superiority of ultrasound over QRS duration to assess LV dyssynchrony, there are no conclusive data on prediction of CRT response either using conventional or more advanced echocardiographic technologies. The Cardiac Resynchronization-Heart Failure (CARE-HF) study is the only large randomized and controlled trial that required direct, ultrasound measurement of cardiac dyssynchrony in a subset of patients with mild to moderate QRS enlargement (= 120–149 ms) (5). However, in the CARE-HF study only 92 patients (11%) underwent CRT based on Doppler echocardiographic indexes of myocardial dyssynchrony. Of consequence, the results cannot be considered exhaustive. It is not unexpected, therefore, that the ECG representation of abnormal cardiac conduction still remains as the main criterion to identify patients with dyssynchronous ventricular contraction. Accordingly, no consensus definition of cardiac dyssynchrony exists as yet from the main cardiologic associations -47, alth


A cutaneous force-frequency relation recording system based on first heart sound amplitude vibrations has been recently validated. Second heart sound can be simultaneously recorded in order to quantify both systole and diastole duration.1- To assess the feasibility and extra-value of operator-independent, force sensor-based, diastolic time recording during stress.We enrolled 161 patients referred for stress echocardiography .The sensor was fastened in the precordial region by a standard ECG electrode. The acceleration signal was converted into digital and recorded together with ECG signal.Both systolic and diastolic times were acquired continuously during stress and were displayed by plotting times vs. heart rate. Diastolic filling rate was calculated as echo-measured mitral filling volume/sensor-monitored diastolic time.Diastolic time decreased during stress more markedly than systolic time. At peak stress 62 of the 161 pts showed reversal of the systolic/diastolic ratio with the duration of systole longer than diastole. In the exercise group, at 100 bpm HR, systolic/diastolic time ratio was lower in the 17 controls (0.74 ± 0.12) than in patients .2* s-1 at peak stress (p < 0.5 vs. rest).Diastolic filling rate increased from 101 ± 36 (rest) to 219 ± 92 ml/mCardiological systolic and diastolic duration can be monitored during stress by using an acceleration force sensor. Simultaneous calculation of stroke volume allows monitoring diastolic filling rate.Stress-induced "systolic-diastolic mismatch" can be easily quantified and is associated to several cardiac diseases, possibly expanding the spectrum of information obtainable during stress. Prior work concerning diastolic duration has been motivated primarily by consideration of diastolic myocardial perfusion time rather than the duration of mechanical events and has been used to assess the HR-dependent effects of pharmacological agents  with fixed values totally independent from the increasing heart rate stress type. Table However at each heart rate the fixed total cardiac cycle time can be differently divided between systole and diastole. At fixed heart rates the diastolic time fraction is determined by factors that modulates systolic duration through modulation of myocyte contraction . ObviousIn the exercise group of this study the systolic time declined as stress intensity increased, with a significant decrease at each level of exercise. From rest to peak exercise, the mean systolic time was shortened by 25 ± 11%. The diastolic time decreased markedly during early exercise and, at a heart rate of 100 bpm, the mean filling time had shortened by 35 ± 16% (by 52 ± 13% at peak stress). Others -30 have At 100 bpm, systolic/diastolic time ratio was lower in the 17 controls (0.74 ± 0.12) than in patients with hypertensive 0.94 ± 0.12), coronary (0.88 ± 0.11), valvular (0.93 ± 0.14) or cardiomyopathy heart (0.86 ± 0.10) disease   with various pharmacologic agents: propranolol increased diastole by slowing HR; dobutamine increased %diastolic time by shortening the QS2; cedilanid increased %diastolic time both by slowing the HR and shortening the QS2; isoproterenol increased HR and shortened the QS2 significantly. These data show that cardiovascular drugs may have significant effects on the relative duration of diastole either by affecting HR or the duration of systole. This may have clinical implications for patients with coronary artery disease and patients with left ventricular hypertrophy, since in both cases coronary flow in mostly diastolic. At a given coronary perfusion pressure, subendocardial perfusion is dependent on the ratio between the time the heart is in diastole and the duration of a complete heart cycle. The diastolic time fraction indicates the duration of absence of compression of intramural vessels during a heart beat and is used as input into theoretical models on coronary perfusion . Additional indexes include the peak velocity of the A wave (Apeak) and the ratio of the Epeak and Apeak velocities (E/A) [A potential limitation of this study is the lack of information regarding Doppler indexes or diastolic function or dysfunction during stress. Doppler echocardiography is the preferred method for non-invasive diastolic function assessment. Doppler-derived indexes have been used to characterize diastolic function in numerous cardiac disorders, including heart failure, myocardial infarction, hypertrophic cardiomyopathy, and hypertension. In current practice, most diastolic function indexes are derived by visual inspection of transmitral E- and A-waves. These shape-derived indexes include peak velocity of the E-wave (Ees (E/A) .Vp), to annular velocities derived from Doppler tissue imaging , but there is no consensus as to whether these indexes are truly load independent [During exercise E- and A-waves become difficult to separate and discern when the A-wave merges with the E-wave and covers more than two-thirds of the E-wave deceleration, which typically occurs at heart rate > 100 beats/min . Furtherependent -45.It has been noted that E' is load independent in patients with chronic ischemic syndrome  but has Another potential limitation is the fact that cardiologic diastole includes filling phases, but also isovolumic relaxation . Its incFive (3 %) of the 161 patients had stress induced ischemia. The low rate of test positivity depends on many factors. The test indication class was not always I or IIa: low appropriateness in a high volume laboratory setting mainly depends on too often repeated tests in the absence clinical changes . Second,An operator independent cutaneous force sensor based on first heart and second heart sound vibrations amplitude recording may be utilized to automatically quantify cardiological systolic and diastolic duration.A stable, reproducible, and consistent first heart sound and second heart sound signal has been obtained in all patients and utilized as a time markers to continuously assess cardiologic systole and diastole during exercise, dipyridamole and pacing stress echo. Diastolic time was greater and systolic/diastolic time lower in the 17 control subjects than in the patients. At higher heart rates, the increased systolic/diastolic ratio was accentuated in patients with systemic hypertension, or coronary, dilated or valvular heart disease, reflecting the relatively prolonged systole and shortened diastole in these patients.Simultaneous calculation of stroke volume with echocardiography allowed quantifying diastolic filling rate and its increase with stress.Portability of the sensor and simple remote transmission of the signal could allow telemonitoring in chronic heart failure patients.The authors declare that they have no competing interests.TB conceived this study, performed the data analysis, and drafted the manuscript; LV, CP, EPa, LP, DAR and MP were responsible for data collection and revised the manuscript; VG, EB, FF and MG were responsible for technology development and digital signal processing; GA gave a contribution to data discussion; EPi gave a contribution to the preparation of study design, data discussion, and critical revision of the manuscript. All authors read and approved the final manuscript.


We sought to evaluate the relation between atrial fibrillation (AF) and the extent of myocardial scarring together with left ventricular (LV) and atrial parameters assessed by late gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) in patients with hypertrophic cardiomyopathy (HCM).AF is the most common arrhythmia in HCM. Myocardial scarring is also identified frequently in HCM. However, the impact of myocardial scarring assessed by LGE CMR on the presence of AF has not been evaluated yet.87 HCM patients underwent LGE CMR, echocardiography and regular ECG recordings. LV function, volumes, myocardial thickness, left atrial (LA) volume and the extent of LGE, were assessed using CMR and correlated to AF. Additionally, the presence of diastolic dysfunction and mitral regurgitation were obtained by echocardiography and also correlated to AF.-2 versus 46 ± 18 ml·m-2, p = 0.0002, respectively). The mean extent of LGE was higher in HCM patients with AF than those without AF . When adjusting for age, gender and LV mass, LGE and indexed LA volume significantly correlated to AF . By echocardiographic examination, LV diastolic dysfunction was evident in 35 (40%) patients. Mitral regurgitation greater than II was observed in 12 patients (14%). Multivariate analysis demonstrated that LA volume and presence of diastolic dysfunction were the only independent determinant of AF in HCM patients . Receiver operating characteristic curve analysis indicated good predictive performance of LA volume and LGE (AUC = 0.74 and 0.64 respectively) with respect to AF.Episodes of AF were documented in 37 patients (42%). Indexed LV volumes and mass were comparable between HCM patients with and without AF. However, indexed LA volume was significantly higher in HCM patients with AF than in HCM patients without AF (68 ± 24 ml·mHCM patients with AF display significantly more LGE than HCM patients without AF. However, the extent of LGE is inferior to the LA size for predicting AF prevalence. LA dilation is the strongest determinant of AF in HCM patients, and is related to the extent of LGE in the LV, irrespective of LV mass. Hypertrophic cardiomyopathy (HCM) is a complex and relatively common form of genetic heart disease and the most frequent cause of sudden death in the young . HCM is Atrial fibrillation (AF) is the most common arrhythmia in HCM -5. In geCardiovascular magnetic resonance (CMR) has a high spatial resolution, is considered the gold standard for in vivo determination of left ventricular (LV) mass and volumes, and enables precise quantification of wall thickness and dimensions ,13. AddiGiven the association between the extent of LGE with progressive LV dilation, ventricular arrhythmias and markers of sudden death in HCM patients we hypothesized that the extent of LGE might also be associated with the presence of AF -18. Thusst Department of Medicine, University Hospital of Mannheim, Germany and the Department of Cardiology, VU University Medical Center, Amsterdam, the Netherlands. All HCM patients were diagnosed based on conventional criteria; left ventricular hypertrophy ≥ 15 mm on two-dimensional echocardiography in the absence of another disease that could account for the hypertrophy [In total, 102 consecutive HCM patients referred for CMR were selected between February 2003 and December 2006 at 2 referral centers: 1ertrophy . The wor2. After obtaining standard 4, 3 and 2 chamber long axis cines, a stack of 9 to 12 short-axis slices was used for full coverage of the left and right ventricle. The LGE images were obtained 10-15 min after intravenous administration of 0.2 mmol·kg-1 gadolinium-DTPA , using an inversion recovery turbo Fast Low Angle Shot (FLASH) sequence with 6 mm slice thickness at the same position as the long- and short-axis cines in end diastole [All studies were performed using a 1.5 Tesla whole body imaging system . A dedicated four-element, phased-array body coil was used. Images were acquired during breath-holds in mild expiration. Scout images  were obtained for planning of the final double-oblique long-axis and short-axis views. To evaluate functional parameters, ECG-gated cine images were then acquired using a balanced segmented steady state free precession (trueFISP) sequence. Typical scan parameters were: 5 mm slice thickness with 5 mm interslice gap, temporal resolution 35 ms, repetition time 3.2 ms, echo time 1.2 ms, flip angle 60 degrees, and typical in-plane spatial resolution 1.4 × 1.8 mmdiastole . The invLV end diastolic volumes, LV end-systolic volumes, LV stroke volume, LV ejection fraction and LV myocardial mass were assessed off-line from the serial short-axis true FISP cine loops using dedicated commercially available software . In addition to volumetric measurements, one-dimensional measurements of LV end diastolic dimensions (LVEDD), posterior wall thickness (PWT) and maximum interventricular septum wall thickness (SWT) were measured from end diastolic short-axis views. LA volumes were measured at end systole by the biplane area-length method on 4 and 2 chamber long axis views .The extent of LGE was quantified using semi-automatic commercially available software  defining a signal intensity over 2 standard deviations above the mean signal intensity of a region of interest drawn in remote myocardium in the same slice as where the LGE was present . The extStandard echocardiographic images were obtained using a Vivid 7 machine  with a 2.5 MHz phased array transducer at end-expiratory apnea.global) was used. All echocardiographic measurements were averaged over three consecutive cardiac cycles, measured by a single investigator blinded to all other variables. LV diastolic dysfunction was defined as follows: [global ≤ 12.9 cm/s if age <40; E'global ≤ 10.2 cm/s if age 40-59; and E'global ≤ 7.2 cm/s if age ≥ 60. Color Doppler flow imaging was used for semiquantitative assessment of mitral regurgitation.Peak velocity of early (E) and late (A) wave of transmitral flow and E-wave deceleration time (DT) were measured from the pulsed-wave Doppler (PWD) obtained at the tip of mitral leaflets. Tissue Doppler imaging (TDI) was used to obtain early diastolic LV myocardial velocities (E') in the apical 4- and 2-chamber views with a 2 mm sample volume placed at the lateral, septal, anterior, and inferior mitral annulus. The average of the four annular sites  and symptomatic HCM patients (NYHA II-IV), an unpaired, 2-tailed student's t-test was also used. Pearson's correlation was used to correlate extent of LGE with LA volume and LV mass. Partial correlation was used to correct the correlation between the extent of LGE and LA volume with presence of AF for age, gender and LV mass. Multivariate analysis was performed with logistic regression analysis using block entry of the following variables: LA volume, extent of LGE, LV mass, presence of mitral regurgitation, presence of diastolic dysfunction, age and gender to evaluate if these variables were independent predictors of AF, provided to have a p < 0.10 in univariate analysis. Area-under-curve analysis was performed to evaluate if LA volume, extent of LGE and LV mass would increase the likelihood of having AF in HCM patients. Additionally, receiver-operator-curve analysis was used to determine the optional cut-off value of LA volume and extent of LGE to discriminate patients at increased risk of AF from patients without. All results were considered statistically significant when p < 0.05. Analyses were performed with Statistical Package for Social Sciences .In 87 of included HCM patients, AF was documented in 37 HCM patients (43%) at time of initial diagnosis or during follow-up. Baseline characteristics are presented in table Age, LV ejection fraction, LV end systolic volume, and LV mass were all comparable between HCM patients with and without AF. However, LV end systolic volume tended to be larger and LV ejection fraction tended to be lower in HCM patients with AF, see table In general, in our collective LGE occurred in a patchy distribution with multiple foci within hypertrophied regions of the intervenricular septum, the anterior and posterior walls. In 14 patients LGE was limited at the RV insertion points (16/59 = 27%). In two patients LGE was also present in the lateral wall (2/59 = 3%). In 13 patients LGE (13/59 = 22%) was diffuse trans-septal and RV septal. In these patients, 10 had AF. However, the small sample size precludes any firm conclusions.The mean extent of LGE was higher in HCM patients with AF compared to those without . However, the prevalence of AF was comparable between HCM patients with LGE to those without LGE . When adjusting for age, gender and LV mass, both the extent of LGE and LA volume moderately correlated to AF . Interestingly, LA volume moderately correlated to the extent of LGE , irrespective of LV mass, which did not correlate with LA volume . LV mass also did not correlate with the extent of LGE .LA volume was significantly larger in HCM patients with dystolic dysfunction than in patients without diastolic dysfunction (p = 0.04). In HCM patients with diastolic dysfunction the mean extent of LGE tended to be higher compared to HCM patients without diastolic dysfunction. However, this comparison did not reach a significant level .With multivariate logistic regression analysis, a model using the extent of LGE, LA volume, presence of mitral regurgitation and presence of diastolic dysfunction to predict AF in HCM patients had an r-square of 0.31, p < 0.01, and revealed that only LA volume and diastolic dysfunction were independently associated with a history of AF in HCM patients .2 has optimal discriminative power to predict AF, yielding a sensitivity of 80.8% and specificity of 64.1%. With respect to the extent of LGE, an optimal cut-off value of 3.3% was found to have a sensitivity of 76.9% and a specificity of 59.0%, see figure The univariate association between the presence of AF with LA volume and extent of LGE was confirmed with ROC analysis, see figure The present CMR study demonstrates that HCM patients with AF had larger LA volumes and displayed more LGE than HCM patients without AF. LA volume and diastolic dysfunction were independently associated with a history of AF in HCM patients. However, among these two parameters LA volume was the strongest independent determinant of AF. Additionally, LA volume moderately correlated to the extent of LGE irrespective of LV mass. Also, in symptomatic HCM patients in this study, LV end-systolic volumes and LA volumes were larger and extent of LGE was higher compared to asymptomatic HCM patients, which is in line with previous reports ,22. InteAF is a commonly reported complication of HCM ,4,8,10. -2 had an optimal discriminative power to predict AF, yielding a sensitivity of 81% and a specificity of 64%. This cut-off value is comparable with the results from Losi et al, who found a cut-off value of 44 ml·m-2 determined with echocardiography [In a community-based HCM population, Olivotto et al. found that the strongest predictor of AF was increased LA volume, independent of age and functional NYHA functional class . In addiiography . The striography .In addition, AF was associated with LGE in HCM patients. However, not the presence but the extent was shown to be indicative for AF. This is in line with the findings of a necropsy study of HCM patients performed by Yamaji et al , who fou2+-handling may ultimately lead to diastolic dysfunction of the LV and subsequent LA dilation and explain the relation between the extent of LGE, LA dilation and subsequent AF [The underlying mechanisms relating LV LGE with AF are unknown. The histological background of LGE in HCM patients has been suggested to be myocardial scarring and/or interstitial fibrosis . Focal aquent AF ,27. ThisIn contrast to patients with hypertension and in normal population ,29, LV mMitral regurgitation is very common in patients with HCM. Also, in our study population mitral regurgitation was present in 39 (45%) patients. However, mitral regurgitation was not a independent predictor of AF in HCM patients. Similar to our results, Losi et al. found that mitral regurgitaiton was not a determinant of AF in any model of multivariate analysis .-2 determined with CMR as an indication to aggressively search for the presence of AF.Should further studies confirm the pathogenic role of fibrosis in diastolic dysfunction and subsequent LA dilation in HCM, different treatment options aimed at stopping or even reversing the process of fibrosis could gain clinical importance. For example, angiotensin II blockade, statins and aldosteron antagonists, have already been demonstrated experimentally to cause regression of fibrosis, hypertrophy and disarray in animal HCM models -32. MoreFor cine and LGE imaging, we used a gap of 5 and 4 mm between slices for full coverage of the left ventricle, thereby omitting 40 to 50% of total myocardium. This may potentially have introduced inaccuracy of volume and mass measurement; however, in a comparative study performed by Hogan et al, contiguous acquisition of slices and acquisition with 4 mm showed comparable accuracy and yielded comparable volumes . As mentIn conclusion, HCM patients with a history of AF display significantly more LGE than HCM patients without AF. However, the extent of LGE is inferior to the LA size for predicting AF prevalence. LA dilation is the strongest determinant of AF in HCM patients, and is related to the extent of LGE in the LV, irrespective of LV mass.CMR: cardiovascular magnetic resonance; AF: atrial fibrillation; LGE: late gadolinium enhancement; HCM: hypertrophic cardiomyopathy; EF: ejection fraction; LV: left ventricular; LA: left atrium; trueFISP: Balanced segmented steady state free precession.The authors declare that they have no competing interests.TP performed and evaluated CMR images, participated in study-design, figures and tables and drafted the manuscript. TG contributed equally to the writing of this manuscript. SF participated in study-design and evaluation of CMR data. CD participated in the revision of the manuscript and the evaluation of the echocardiograpical data. AS participated in study design and its coordination. DH participated in collection and evaluation of clinical data. TS participated in study-design and revision of the manuscript. CW participated in study-design and statistical analysis. DD participated in study-design and evaluation of CMR-images. SS participated in study-design and evaluation of CMR-images. AvR was responsible for the revision of the manuscript. MB Participated in study-design, scientific and clinical advice concerning HCM and was responsible for the revision of the manuscript. All authors read and approved the final manuscript.


To evaluate whether myocardial performance index detects a subclinical impairment of left ventricular systolic and diastolic function in patients with early stage of type 2 diabetes, without coronary artery disease, with or without hypertension. Furthermore, to evaluate whether some echocardiographic parameters relate to the metabolic control. Fourty-five consecutive male patients (mean age 52.5 years) with type 2 diabetes mellitus of recent onset (23 hypertensives and 22 normotensives) and 22 age matched healthy controls males were analysed. All participants had normal exercise ECG. All subjects underwent standard and Doppler echocardiography for the assessment of the isovolumic Doppler time interval and Doppler-derived myocardial performance index. In all diabetic patients a glycated haemoglobin test was also performed.No differences were observed in blood pressure, heart rate, and conventional echocardiographic parameters comparing the 2 subgroups of diabetic patients and the controls. Myocardial performance index was significantly higher in diabetic patients independently of the hypertension occurrence, compared to the controls . Myocardial performance index correlated to glycated haemoglobin significantly  in both diabetic subgroups. Thus, an early involvement of left ventricular performance was shown by myocardial performance index in patients with type 2 diabetes of recent onset without coronary artery disease, independently of the hypertension presence. These abnormalities can provide a feasible approach to detect a pre-clinical diabetic cardiomyopathy and could be useful for an indirect assessment of the metabolic control. A primary diabetic cardiomyopathy represents a high risk factor of heart failure in the absence of ischemic, valvular and hypertensive heart disease in the diabetic population -3. Diabe1c) test. Diabetes mellitus was diagnosed according to the criteria of the American Diabetes Association [1c was determined by the HPLC method. Blood sample for analysis was obtained after 8-hours minimum overnight fast and before oral antidiabetic drugs. Hypertension was defined as recommended from the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [2. Patients with history of myocardial infarction, chronic stable angina pectoris, previous coronary revascularization, regional wall-motion abnormalities in rest echocardiography, significant valvular disease at echocardiography, significant rest ECG abnormalities suggestive of myocardial ischemia, symptoms or ECG signs of ischemia on exercise stress test, arrhythmias, congestive heart failure, and chronic obstructive pulmonary disease were excluded from the study. The local medical Ethic Committee approved the study protocol. Written informed consent was obtained from all patients.The study population consisted of 45 consecutive male patients with type 2 diabetes mellitus of recent onset (23 hypertensives and 22 normotensives) and 22 healthy controls males. The patient population was recruited from the Operative Unit of Internal Medicine, Montecchio Emilia Hospital, IT between July 2006 and December 2006. All partecipants had normal exercise ECG and none was a smoker. All subjects underwent standard and Doppler echocardiography and all diabetic patients also a glycated haemoglobin . Data are expressed as means + standard deviation. Comparison among the 3 groups for various parameters was performed by 1-way analysis of variance (ANOVA) and the post-hoc Tukey test for multiple comparisons, and two tailed Student's t test for paired data were applied to evaluate differences between controls and patient groups. The relationship between parameters were evaluated by means of simple linear regression data analysis. The The clinical characteristics of the studied population are shown in Table The echocardiographic characteristics of the three study groups are listed in Table pv/Apv 1.0 in both diabetic populations vs. 1.4 in controls, p < 0.01; DT 182 msec and 190 msec in diabetics respectively normotensives and hypertensives vs. 139 in controls, p < 0.01), although within the normal range  and inversely with ET . No correlations were found between some clinical parameters  and echocardiographic parameters (LV mass index, wall thickness, LV EF or FS, E/A ratios and DT.MPI was significantly higher in both diabetic groups compared to controls Table . This waIn a previous study Mishra and coworkers have shown a limited role for MPI in the assessment of cardiac function in populations with multiple coronary risk factors but free of clinical cardiovascular disease , althoug1c (Figure The mechanisms behind LV performance dysfunction remain largely unknown. In normotensive and free of ischemic heart disease patients, the metabolic abnormalities may play a major role. In fact, we found a correlation between myocardial performance index and HbAc Figure . NeverthOur findings may have important clinical implications to the early identification of subclinical myocardial performance abnormalities with normal cardiac function at the conventional echocardiography. MPI provides an easy early phase index of diabetic cardiomyopathy that precede diastolic dysfunction, which monitors the natural history of the diabetic disease. Furthermore, MPI is useful for the indirect assessment of the metabolic control or for suggesting an early pharmacological treatment. Finally, MPI detects whether such abnormalities can modify or revert as a response to an optimal metabolic control and/or pharmacological treatment. The early diagnosis of a pre-clinical diabetic cardiomyopathy with MPI is useful for the appropriate clinical testing of new therapeutic approaches in the diabetic population.A study limitation is represented by the patients sample, which is limited in size. In addition, the diabetes therapy was different in the two groups of patients although according to the guidelines. Moreover, we know that the exercise ECG in diabetic patients has a low sensitivity and subclinical atherosclerosis cannot be fully excluded. However, our patients were asymptomatic, free of previous history of coronary artery disease and the diabetes was of recent onset. We believe that the exercise test in patients with these characteristics can represents a reliable test with a higher sensitivity.Beside, in common with other investigations on the MPI, we did not evaluate the effects of abnormalities of late diastolic compliance. However, when present, these are associated with raised LV filling pressure, which would shorten IRT and thus reduce the MPI, counterbalancing the prolongation due to those of early diastole. Finally, no outcome data are available at the moment.In conclusion, subtle abnormalities of LV myocardial performance are detected by means of MPI during the early stage of type 2 diabetes, independently of the hypertension presence, and it broadens the spectrum of pre-clinical diabetic cardiomyopathy.PP carried out all the two-dimensional and Doppler echocardiograms and participated in the sequence alignment and drafted the manuscript, FBS participated in the sequence alignment and drafted the manuscript, EC participated in the sequence alignment, AP participated in the sequence alignment, RI participated in the sequence alignment, MM selected the diabetic patients. MG participated in the design of the study and performed the statistical analysis, AB participated in the design of the study and performed the statistical analysis, MDC participated in the design of the study and drafted the manuscript, VM selected the patients. All authors read and approved the final manuscript.


As coronary artery disease may also occur during childhood in some specific conditions, we sought to assess the feasibility and accuracy of perfusion cardiovascular magnetic resonance (CMR) in paediatric patients.First-pass perfusion CMR studies were performed under pharmacological stress with adenosine and by using a hybrid echo-planar pulse sequence with slice-selective saturation recovery preparation. Fifty-six perfusion CMR examinations were performed in 47 patients. The median age was 12 years (1 month-18 years), and weight 42.8 kg (2.6-82 kg). General anaesthesia was required in 18 patients. Mean examination time was 67 ± 19 min. Diagnostic image quality was obtained in 54/56 examinations. In 23 cases the acquisition parameters were adapted to patient's size. Perfusion CMR was abnormal in 16 examinations. The perfusion defects affected the territory of the left anterior descending coronary artery in 11, of the right coronary artery in 3, and of the circumflex coronary artery in 2 cases. Compared to coronary angiography, perfusion CMR showed a sensitivity of 87% (CI 52-97%) and a specificity of 95% (CI 79-99%).In children, perfusion CMR is feasible and accurate. In very young children (less than 1 year old), diagnostic image quality may be limited. Coronary artery disease (CAD) in paediatric patients may occur after surgery for congenital heart disease involving the coronary arteries, after surgery for congenital coronary anomalies or in patients with an inflammatory disease affecting the mid- and small-size arteries such as Kawasaki disease or Takayasu arteritis -3. ThereExercise-electrocardiography, stress echocardiography, quantitative x-ray coronary angiography (QCA), single-photon emission computed tomography (SPECT) and positron emission tomography (PET) have been so far the available techniques to evaluate myocardial perfusion. QCA is still the reference standard for detecting or quantifying CAD. Radionuclide perfusion imaging suffers from some attenuation artefacts and suboptimal spatial resolution; both techniques necessitate exposure to ionising radiation. As children may need repeated evaluation during long-term follow-up, a non-invasive and radiation-free technique for evaluating the myocardial perfusion is advantageous. Perfusion cardiovascular magnetic resonance (perfusion CMR) using the first-pass kinetics of a gadolinium bolus for detecting myocardial ischemia has shown promising results in clinical trials in adult patients with known or suspected CAD -7. In chAims of this study were to assess the feasibility of performing perfusion CMR in paediatric patients and to determine the diagnostic performance of CMR compared to QCA.Between January 2003 and June 2006, 47 consecutive patients underwent 56 CMR examinations for evaluation of myocardial perfusion. Seven patients had two examinations and one patient was evaluated three times. The median age was 12 years (range 1 month - 18 years) and the median weight 42.8 kg (range 2.6 kg - 82 kg). The cardiac diagnoses are listed in table Coronary surgery included aortocoronary bypass to the left coronary artery in 5 patients, a venous patch augmentation of the left coronary artery in 4, an aortocoronary bypass to the right coronary artery (RCA) in 2 and reduction of a coronary aneurysm with patch augmentation of a nearby stenosis of the RCA in one. Two patients underwent catheter-guided stenting of a coronary stenosis following Kawasaki disease.All CMR examinations were performed using a 1.5 T scanner  and a phased-array cardiac coil. The images were acquired during breath holding in all patients, by asking the patients to stop breathing in end-inspiration (n = 38) or by stopping mechanical ventilation in the same position (n = 18). Patient's HR and ECG tracing were continuously monitored; blood pressure was measured at 2 minutes intervals.The protocol included cine steady-state free precession sequences in a vertical and horizontal long-axis plane, as well as a stack of short-axis acquisitions covering the entire left ventricle for evaluation of left ventricular volumes and function. The steady-state free precession images were acquired at rest with following parameters: TE minimum, flip angle 45°, bandwidth 125 kHz, matrix 224 × 224, number of excitations 1, field of view 26-45 cm, slice thickness 6-8 mm with 1-3 mm gap depending on the body size, retrospective gating with 20 images reconstructed per cardiac cycle.®, Schering, Berlin Germany) in a dose of 0.1 mmol/kg injected in a cubital vein through a large bore cannula at flow rate of 5 ml/sec and followed by a saline flush of 25 ml, flow 5 ml/sec. Five to seven slices were acquired every second heart beat in a short axis plane  using an hybrid echo-planar pulse sequence with selective notch pulse preparation [Myocardial perfusion was assessed, in accordance to our standard protocol, under pharmacological stress with intravenous adenosine in a dose of 0.14 mg/kg/min during 3 minutes. The myocardial signal increase during first-pass was evaluated during a GADOLINIUM bolus injection  by acquiring images in long- and short-axis planes with a inversion-recovery-prepared gradient-recalled echo pulse sequence and with an adjusted inversion time (180-210 ms) in order to null viable myocardium. Acquisition parameters: echo time minimum full, matrix 256 × 192, number of excitations 2, flip angle 20°, bandwidth ± 31.25 KHz, 24 views per segment, rectangular field of view 26 × 20 cm to 38 × 28 cm depending on patient's size, slice thickness 8 mm, trigger delay depending on HR.Late gadolinium enhancement imaging (LGE) was performed 10-15 minutes after injection . The ventricular function was calculated as previously described with the MASS analysis software package  . First-p®, Sintetica SA, Mendrisio, Switzerland). In small children or in cases in whom anatomy precluded selective cannulation of the coronary arteries, contrast was injected into the aortic root at a dose of 1-1.5 ml/kg and with the maximal flow velocity allowed by the size of the catheter (1-2 ml/sec) by using a power injector. The images were acquired with a frame rate of 25/sec in the standard projections for visualisation of the right and the left coronary artery as previously described [X-ray coronary angiographies were performed during cardiac catheterisation with a biplane Integris BH 5000 cardiovascular system . Selective coronary angiography was performed by hand injection of an ionized contrast agent (Iopamiroescribed .Quantitative coronary angiography (QCA). X-ray coronary angiographies were analysed using Inturis Cardio View software, Release 1.2 . Before measuring the diameter of the coronary arteries, calibration was obtained by comparing the diameter of the catheter shown on the angiographic images with the catheter diameter in French supplied by the manufacturer. In order to increase the accuracy of the measurements the external diameter of the catheter was measured when empty of contrast. Stenosis was defined as a narrowing of a coronary artery with a reduction of the vessel diameter of ≥ 50%.An experienced cardiologist (CB) blinded to the results of perfusion CMR analyzed the QCAs.Numerical data are reported as mean values and standard deviations or as median values and ranges where appropriate. Accuracy was evaluated by calculating sensitivity and specificity  of perfusion CMR vs. QCA. A p value < 0.05 was considered as statistically significant. The Research Ethics Board of our institution approved the study. Parents gave their informed consent for the perfusion examination.Fifty-six perfusion CMR examinations were performed in 47 consecutive patients. Perfusion CMR was successfully performed and diagnostic image quality was obtained in 54 of 56 examinations. The image quality of two examinations was insufficient, due to lack of compliance in a 10 years-old patient and to the very small body size (2.7 kg) in a 3 weeks-old newborn. The overall mean examination (scanning) time was 67 ± 19 min. Baseline mean heart rate (HR) was 78 ± 19 bpm, systolic blood pressure (BP) 102 ± 17 mmHg, diastolic BP 58 ± 13 mmHg. Peak HR under hyperaemia was 100 ± 19 bpm, systolic BP 99 ± 22 mmHg, diastolic BP 53 ± 15 mmHg.Perfusion CMR was performed in general anaesthesia in 18 patients. In 23 examinations the acquisition parameters were modified according to patient's size. Slice thickness was reduced from 8 to 7 mm in 16, the gap between slices from 4 to 3 mm in 19 studies and to 2 mm in 4. A field of view smaller than 30 × 23 cm was used in 19 studies, all patients younger than 10 years. The injection velocity of the CM bolus was adapted to the size of the cannula and reduced from 5 to 4 ml/sec in 4 cases, to 3 ml/sec in 5 and to 2 ml/sec in the youngest child.LGE was performed in addition to the first-pass acquisitions in 13 cases. Indication for performing LGE acquisitions consisted of a patient's clinical history suggesting potential occurrence of myocardial scar, i.e. a positive history for myocardial infarction, myocarditis or cardiomyopathy. In one case the image quality of LGE was insufficient due to arrhythmias.Minor technical problems occurred during 3 examinations and consisted of triggering difficulties, software problems, and initial IV line dysfunction in one patient each. The technical difficulties were transient and the examination could be successfully concluded in all 3 cases.All examinations were performed without any significant medical complications. In one child under general anaesthesia atropine was given to treat bradycardia (not related to adenosine), one patient showed a self-limiting mild arterial hypotension, and a girl with a total occlusion of left anterior descending coronary artery (LAD) experienced chest pain during adenosine infusion, but remained haemodynamically stable.2 and mean ejection fraction (EF) was 54.5 ± 9.8%. A dilated LV (LVEDV > 100 ml/m2) [Data about left ventricular (LV) volume and function were available for 53 examinations. Mean LV end-diastolic volume (LVEDV) was 79.9 ± 24.6 ml/mReduced function with EF < 45% was measured in 9 patients: 7 of these presented with abnormal coronary arteries, including Kawasaki disease in 5, Bland-White Garland syndrome in one, and LAD narrowing after arterial switch operation in one. Five of these patients had previous surgery of the coronary arteries and 3 had a history of myocardial infarction.A normal perfusion CMR study was observed in 38 exams. Perfusion was abnormal in 16 examinations with a perfusion deficit in the territory of LAD in 11, of RCA in 3, and of left circumflex coronary artery (LCX) in 2 cases . Normal coronary arteries were found in 20 patients and a coronary artery stenosis in 8, consisting of a LAD stenosis in 5, RCA stenosis in 2, and stenosis of the LCX in one case. Aneurysmatic enlargement of the coronary arteries was described in 3 children after Kawasaki disease.Perfusion CMR findings were concordant with QCA in 29 and discordant in 2 cases (Table Compared to QCA perfusion CMR showed a sensitivity of 87% (CI 52%-97%), and a specificity of 95% (CI 79%-99%). Agreement between the perfusion CMR results and the intraoperative findings was 100%.The clinical impact of perfusion CMR as a non-invasive technique for the assessment of ischemic heart disease is rapidly increasing . In chilTo our knowledge, this is the largest study reporting the use of perfusion CMR in paediatric patients. Our data demonstrate a feasibility of 96%, and a high accuracy, with a sensitivity of 87% and a specificity of 95%. These results are similar to those reported in adults in single-centre . The larThe paediatric experience reported so far in assessing ischemic disease with perfusion CMR is scarce ,17. One Several larger perfusion CMR trials established key components of perfusion pulse sequences ,14. HoweWe utilized a gadolinium dose of 0.1 ml/kg, which has been demonstrated to give the best results in adults, also in all our paediatric patients. In contrast, the gadolinium injection rate needed to be reduced and adapted to the size of the intravenous cannula in 10 patients. Since Gebker et al. showed that myocardial enhancement and upslope are largely independent from the injection rate of gadolinium bolus as long as the injection speed is not below 3 ml/sec , we targSusceptibility artefacts originating at the interface between blood (high gadolinium concentration) and the myocardium (low gadolinium concentration) may occur more often in small hearts with thin walls, in which fewer pixels are imaged transmurally. Kellman et al. demonstrated larger artefacts at lower spatial resolution . It is tHigh HR in children, caused by both, an elevated baseline HR and a more sensitive response to adenosine, which we could consistently observe in our study, require an efficient and robust ECG-triggering system. The relatively new vector cardiac gating systems usually yield to a good triggering, even in higher heart rate, without need for any additional adjustment.In spite of all these challenges, by carefully tailoring the examination conditions in each individual case, we were able to obtain a diagnostic imaging quality in 96% of the examinations. Perfusion CMR was misleading in two cases: in 3 weeks-old newborn weighting 2.7 kg in whom the rate of gadolinium injection needed to be reduced to 2 ml/sec, and in another child unable to be compliant to hold his breath.On the base of our initial experience described in this paper, we are now able to provide some recommendations on how to optimise the preparation of the patient and the acquisition of the images. Firstly, we recommend performing perfusion CMR only in children older than 1 year or weighting more than 10 kg. The possibly largest i.v. cannula should be inserted in the forearm of the patient, allowing gadolinium injection rate of at least 3 ml/sec. Secondly, image acquisition should be performed during breath-holding in conscious and anaesthetized patients. Thirdly, the same gadolinium dose of 0.1 mmol/kg as in adult can be used. Fourthly, spatial resolution can be optimise by reducing slice thickness and field of view below 30 × 23 cm, if a matrix of 128 × 128 is used, keeping in mind that an ideal in plane resolution in children might be 1.5-2.5 × 1.5-2.5 mm figure . FinallyThis is a retrospective study concealing some limitations. Firstly, our data present a rather wide range of time intervals between perfusion CMR and QCA. The reason for this is that some QCA data used for comparison had been obtained before perfusion CMR was available as a diagnostic technique in our institution. In these patients catheterisation was not repeated if no clinical suspicion of ischemic heart disease was present at perfusion CMR. Other patients were selected for QCA only, when perfusion CMR findings were abnormal. This more clinically oriented approach may have introduced a selection bias in the patient group undergoing QCA, and may have influenced accuracy. This kind of potentially serious limitation is often encountered in paediatric research, as in children ethical reasons preclude the liberal use of invasive examinations or anaesthesia for research purposes.Secondly, as this study was performed in children, we sought to keep the examinations as short as possible and the patients compliant. Therefore, LGE was not performed consistently in every case, but only if indicated for clinical reasons or if perfusion CMR findings suggested the presence of ischemia and/or scar. Nevertheless, in spite of having applied this single perfusion CMR pulse sequence for evaluation of ischemia, we found a high sensitivity and specificity for the detection of CAD. However, in clinical practice with the suspicion of myocarditis or a storage disease, LGE should be performed as the preferred CMR approach .Finally, as the CMR scans were performed for clinical reasons, we endeavoured to keep the sequence robust and performed only careful changes in the acquisition parameter for adapting them to the patient's size. Testing different "paediatric protocols" in a standardized way was not the aim of our study, but may be needed in the future for further optimisation and validation of the method in the paediatric populationIn the paediatric population, perfusion CMR is feasible and accurate. Age and body size are still limiting factors, and very young children, e.g. < 1 year, are considered suboptimal candidates for this non-invasive technique. However, in older children with suspected coronary alterations perfusion CMR can be recommended as a highly valuable first test as well as an important adjunct to invasive x-ray coronary angiography.The authors declare that they have no competing interests.EVB conceived and designed the study and gave a major contribution to the draft of the manuscript and its revision. CB performed and analysed the data of coronary angiography and contributed to the draft of the manuscript. UB helped to design the study and to revise the manuscript. CJK was involved in data acquisition and draft of the manuscript. JS conceived and designed the study and gave a major contribution to the draft of the manuscript and its revision. All authors read and approved the final manuscript.


The treatment of patients with aortic regurgitation (AR) or mitral regurgitation (MR) relies on the accurate assessment of the severity of the regurgitation as well as its effect on left ventricular (LV) size and function. Cardiovascular Magnetic Resonance (CMR) is an excellent tool for quantifying regurgitant volumes as well as LV size and function. The 2008 AHA/ACC management guidelines for the therapy of patients with AR or MR only describe LV size in terms of linear dimensions (i.e. end-diastolic and end-systolic dimension). LV volumes that correspond to these linear dimensions have not been published in the peer-reviewed literature. The purpose of this study is to determine the effect of regurgitant volume on LV volumes and chamber dimensions in patients with isolated AR or MR and preserved LV function.Regurgitant volume, LV volume, mass, linear dimensions, and ejection fraction, were determined in 34 consecutive patients with isolated AR and 23 consecutive patients with MR and no other known cardiac disease.2 = 0.8, mitral regurgitation r2 = 0.8). Bland-Altman analysis of regurgitant volume shows little interobserver variation . The correlation is much poorer between regurgitant volume and commonly used clinical linear measures such as end-systolic dimension . For a given regurgitant volume, AR causes greater LV enlargement and hypertrophy than MR.There is a strong, linear relationship between regurgitant volume and LV end-diastolic volume index (aortic regurgitation rCMR is an accurate and robust technique for quantifying regurgitant volume in patients with AR or MR. Ventricular volumes show a stronger correlation with regurgitant volume than linear dimensions, suggesting LV volumes better reflect ventricular remodeling in patients with isolated mitral or aortic regurgitation. Ventricular volumes that correspond to published recommended linear dimensions are determined to guide the timing of surgical intervention. The timing of surgical intervention for patients with mitral or aortic regurgitation often depends on the accurate assessment of the severity of the valvular insufficiency and its effect on left ventricular (LV) size ,2. Two-d2), myocardial ischemia or scar, left ventricular hypertrophy, intracardiac shunt, more than mild tricuspid or pulmonic regurgitation, and patients with an irregular cardiac rhythm. Additionally, patients were excluded from the mitral regurgitation (MR) group if they had more than minimal (>10 ml) aortic regurgitation (AR) and from the AR group if they had more than minimal (>10 ml) MR. The analysis comprised 57 patients who underwent CMR evaluation, and included 34 patients  with AR and 23 patients  with MR.This study was a retrospective analysis of patients referred for a clinical CMR evaluation between 2006 and 2009. This study was approved by the Institutional Review Board of St. Luke's and Roosevelt Hospitals. Consecutive patients were included provided 1) they had sufficient mitral or aortic regurgitation to warrant quantification of their regurgitant volume in their clinical report and 2) phase contrast images of pulmonary artery and aortic flow were acquired with a corresponding phantom image for correcting baseline flow offsets . PatientPatients were imaged with a 1.5-Tesla scanner using an 8-element, phased-array coil . Images were acquired with ECG gating and breath holding. Short and long axis cine images were acquired using a steady-state free precession pulse sequence (FIESTA) with the following parameters: TR/TE 3.3 ms/1.4 ms, 20 views per segment, FOV 35 × 35 cm, acquisition matrix 192 × 160, slice thickness 8 mm, slice gap 0 mm, flip angle 45 degrees, receive bandwidth 125 kHz. Phase contrast images were acquired perpendicular to the proximal pulmonary artery and perpendicular to the proximal aorta to quantify flow in these vessels using the following parameters: TR/TE 7.5 ms/2.9 ms, 6 views per segment, Venc 250 cm/s, FOV 35 × 35 cm, acquisition matrix 256 × 128, slice thickness 4 mm, flip angle 20 degrees, receive bandwidth 31.3 kHz. After the clinical scan was completed, additional phase contrast images were acquired of a stationary bottle of water (phantom) for baseline flow correction .2/length) by averaging values from the four and two chamber views. To determine the reproducibility of AR and MR regurgitant volume, a second blinded analysis was made according to the same method.Images were reviewed and analyzed using ReportCard 4.0 software. LV volumes and mass were determined using the semiautomated LV segmentation algorithm which excludes papillary muscles and trabeculations from the LV cavity and which uses a long axis image to define the position of the LV base. RV volumes were determined by manual segmentation of the short axis images. Aortic and pulmonary artery flow values were determined using the resident semiautomated algorithm. Correction for baseline offsets was performed using a phantom phase contrast image as described previously . In someAll analyses were carried out using a standard statistical package . Continuous variables were reported as mean ± SD and categorical variables were reported as percentages. Correlation between regurgitant volumes and left ventricular measures and left atrial volumes were calculated using Pearson's correlation coefficient. Interobserver variability was measured using Bland-Altman analysis and Intraclass Correlation Coefficient. P values were considered significant at < 0.05.2(range = 61 - 100 ml/m2), 103 ± 13 (range = 82 - 121 ml/m2), and 146 ± 19 ml/m2(range = 125 - 186 ml/m2) respectively. Figure 2 = 0.8). There are moderate, linear relationships between aortic regurgitant volume and LV ESVI (r2 = 0.5), LV EDD (r2 = 0.7), and LV ESD (r2 = 0.5). Linear regression is used to determine the LV volumes that correspond to an LV ESD of 55 mm and an LV EDD of 75 mm. These values are listed in Table Demographic and CMR data of the patients with AR are summarized in Table 2(range = 62 - 89 ml/m2), 94 ± 8 ml/m2(range = 82 - 107 ml/m2) and 119 ± 24 ml/m2(range = 98 - 167 ml/m2) respectively. Figure 2 = 0.8). There is a moderate, linear relationship between mitral regurgitant volume and LV ESVI (r2 = 0.5). There are weak linear relationships between mitral regurgitant volume and LV ESD (r2 = 0.3) and mitral regurgitant volume and LA volume (r2 = 0.3). Linear regression is used to determine the LV volume that corresponds to an LV ESD of 40 mm  and severe MR vs. mild MR .We found a greater increase in LV EDVI for a given regurgitant volume in patients with AR compared to those with MR Figure . FurtherCMR has long been accepted as an accurate and reproducible technique for evaluating LV size and function. Good correlation has been obtained by comparing CMR to other established techniques such as echocardiography ,16, cont2 = 0.8). This provides an independent line of evidence supporting the accuracy of MRI for quantifying regurgitant volume and ventricular volumes. We also find MRI is a robust technique. The data show excellent interobserver variation for quantifying regurgitant volume as demonstrated by the Bland-Altman analysis which showed a mean difference of 0.6 ± 4 ml for AR and 4 ± 6 ml for MR.To our knowledge, this is the first CMR study to quantify the physiologic relationship between regurgitant volume and chamber volume in patients with isolated chronic AR or MR and preserved LV function. For both AR and MR, we find a strong linear correlation between regurgitant volume and LV EDVI . Finally, left atrial volume, a parameter which is often used by the echocardiographic community and which has been reported as a reliable estimator of regurgitant volume [2 = 0.3).In our patients with chronic mitral regurgitation, we find the correlation between regurgitant volume and LV EDVI is stronger than with LV ESVI, probably in part because additional factors influence LV ESVI, such as myocardial contractility. The coupling between LV EDVI and regurgitant volume is strong. An rt volume , shows aIn our patients with chronic AR, we find a stronger positive correlation with LV EDVI than with LV ESVI, again probably in part because additional factors influence LV ESVI, such as myocardial contractility. It is interesting to note that for a given regurgitant volume, patients with AR have more LV enlargement and a greater LV mass index than patients with MR. This observation is likely due to the nature of the hemodynamic stress placed on the LV; whereas MR is a pure volume lesion AR is both a pressure and a volume lesion . AdditioMany of the patients in this study were referred for CMR because the severity of the regurgitation could not be accurately determined by echocardiography. The clinical CMR reports included the regurgitant volume, LV dimensions, and LV volumes. Unfortunately, the LV volumes could not be used by the referring physician to determine the timing of surgical intervention because the AHA/ACC management guidelines only refer to linear dimensions. However, the fact that the volumetric measures correlated better to the regurgitant volume than corresponding linear measures suggests the possibility that volumetric measures may be more valuable than linear measures in assessing the response of the left ventricle to chronic MR or AR and in guiding the timing of surgical intervention. It is our hope that the volumetric correlates to the guideline dimensions which are listed in Table Our data are retrospective in nature and only apply to patients with normal or mildly decreased left ventricular function and no other known cardiac disease. These data may not be applicable to patients with other concurrent cardiac diseases and/or LV dysfunction.CMR is a robust technique for quantification of regurgitant volume in patients with AR or MR and preserved LV function. LV volumes show a stronger correlation with regurgitant volume than the linear dimensions recommended in the current management guidelines. These data suggest that LV volumes better reflect ventricular remodeling in patients with isolated mitral or aortic regurgitation.AR: aortic regurgitation; CMR: cardiac magnetic resonance; EDD: end-diastolic dimension; EDVI: end-diastolic volume index; ESD: end-systolic dimension; ESVI: end-systolic dimension index; LV: left ventricular; MR: mitral regurgitation; MRI: magnetic resonance imaging; RV: right ventricular.The authors have no competing interests that relate to this study. Dr Steven Wolff is the owner of NeoSoft, LLC and NeoCoil, LLC.SU and SDW designed the study, performed data analysis, and prepared the manuscript. AS performed statistical analysis. OS and CC performed image acquisition. SK, PN performed data collection. FC performed data analysis. All authors read and approved the final manuscript.


Symptoms in hypertrophic cardiomyopathy (HC) appear to be caused by diastolic dysfunction, myocardial ischemia, left ventricle (LV) outflow obstruction, and atrial fibrillation. However, clinical deterioration and severe heart failure symptoms can be observed in patients without any of these factors. Thus, the aim of this study is to determine the echocardiographic predictors of severe heart failure symptoms in patients with HC.2 = 0.19, p < 0.0001), LV lateral mitral annular systolic TD velocity (LMSa)  and EDt  were found to be the independent predictors for severe heart failure symptoms in forward stepwise regression.86 HC patients were compared according to symptomatic status. Patients with severe heart failure symptoms were older, preponderantly female, had more often LV outflow obstruction and mitral regurgitation, longer E wave deceleration time (EDt), higher E/Ea ratios and lower LV tissue Doppler (TD) velocities when compared to rest of the patients. LV outflow obstruction (r = 0.43, RIn HCM patients with sinus rhythm and normal LV systolic function, LMSa, EDt and LV outflow obstruction are independent predictors of heart failure symptoms. Diastolic dysfunction determined with EDt, occult systolic dysfunction which is detected with TD analysis, and afterload increase as result of LV outflow obstruction seem to be the main echocardiographic factors affecting symptomatic status in HCM patients with sinus rhythm and normal systolic function. Hypertrophic cardiomyopathy (HC) is a complex genetic cardiac disorder with heterogeneous clinical course and expression -3. ExertOne hundred and ten consecutive patients who were admitted to our echocardiography laboratory and diagnosed as HC were included in the study. The diagnosis of HC was based on the demonstration of a hypertrophied, non-dilated left ventricle (LV)  by 2-dimensional echocardiography in the absence of another cardiac or systemic disease capable of producing a similar degree of hypertrophy . A detaiFunctional capacity was assessed according to the New York Heart Association (NYHA) classification by one investigator without knowledge of the laboratory results. Heart failure symptoms are defined by exertional dyspnea and functional limitation (with or without chest pain) independent of whether episodes of impaired consciousness (syncope or presyncope) have occurred ,20. Ten A complete echocardiographic examination was performed with a Vivid Five System  in each patient at rest by a single blinded observer. LV hypertrophy was assessed with 2-dimensional echocardiography according to published criteria . The gre2-dimensional measurements included LV end-diastolic and end-systolic diameters, posterior wall thickness, interventricular septal thickness, and LV ejection fraction . Mitral 2 analysis for proportions and unpaired Student's t test for continuous variables. For comparison of continuous echocardiographic variables in different NYHA functional classes, one way analysis of variance (ANOVA) was used. Forward stepwise regression was performed to determine predictors of severe heart failure symptoms. A probability value < 0.05 was required for retention within the final stepwise regression model. Statistical significance was taken as p < 0.05.Statistical analysis was performed with SPSS 11.5  software. Data are expressed as mean ± SD. Relevant relationships were tested by χThe pattern of LV hypertrophy was asymmetric septal in 76 patients, apical in 4 patients, concentric in 5 patients and isolated posterior wall hypertrophy in 1 patient. Forty-three patients (50%) had basal resting left ventricular outflow tract obstruction with a peak gradient > 30 mmHg. Thirty patients had a positive family history of HC (36%) and 18 patients had a history of sudden death in first degree relatives (22%). At admission 32 (37%) of the patients were asymptomatic (NYHA class I), 37 (43%) had mild symptoms (NYHA class II) and 17 (20%) had severe symptoms (NYHA class III-IV).NYHA class of patients correlated with various echocardiographic and clinical parameters such as age , left atrium diameter , E wave deceleration time , LV outflow obstruction , and LV lateral mitral annular systolic tissue Doppler velocity (LMSa) .The comparison of demographic and echocardiographic parameters including TD velocities of HC patients with and without severe heart failure symptoms (NYHA class I-II vs. NYHA class III-IV) is presented in Table 2 = 0.19, p < 0.0001), LV lateral mitral annular systolic tissue Doppler velocity (LMSa)  and E wave deceleration time (EDt)  were found to be the independent predictors for severe heart failure symptoms in forward stepwise regression.Table LMSa correlated with various echocardiographic and clinical parameters such as left atrium diameter , maximal wall thickness , and NYHA functional class .EDt correlated with age , NYHA functional class , isovolumetric relaxation time .EDt gets longer  and LMSa decreases  with increasing NYHA functional class .In 43 patients without LV outflow obstruction, only three patients had severe heart failure symptoms. Severely symptomatic non-obstructive patients had significantly larger left atrium diameters  and lower basal septal Ea velocities (1.4 ± 0.8 cm/s for class I vs. 3.8 ± 2 cm/s) when compared to the rest of the non-obstructive HC patients. Because of the low number of severely symptomatic patients in non-obstructive group, no further statistical analyses were performed.In the present study, we found that NYHA functional class of the HC patients correlated with various echocardiographic and clinical parameters such as age, left atrium diameter, E wave deceleration time (EDt), LV lateral mitral annular systolic tissue Doppler velocity (LMSa), and LV outflow obstruction. Besides these findings, we have shown that EDt, LMSa, and LV outflow obstruction independently predict the presence of severe heart failure symptoms in HC patients with sinus rhythm and normal LV ejection fraction. LMSa is lower and EDt is longer in patients with higher NYHA class which reflects disease severity.In HC patients, limiting symptoms of exertional dyspnea typically occur in the presence of preserved systolic function and a non-dilated LV ,4. SymptDoppler echocardiographic evaluation of trans-mitral LV filling velocities is widely used to assess LV diastolic function. However, most studies ,28 have Similar to our findings, the association between tissue Doppler variables and heart failure symptoms were demonstrated in several trials. Tissue Doppler derived indexes were found to be correlated with exercise capacity and NYHA functional class in HC patients ,33, but We did not observe statistically significant differences in systolic and diastolic TD velocities of left and right ventricle  between HC patients with and without LV outflow obstruction. These findings were in accordance with previously published studies ,35.Assessment of symptom severity may be highly subjective, encumbered by the heterogeneous presentation of the patients. So, EDt and LMSa may guide the clinician in deciding the severity of the disease and in making the decision for further invasive therapies. Patients with LV outflow obstruction, longer EDt, and lower LMSa seem to be under risk of clinical deterioration as they have more severe symptoms, but this data will have to be validated with further prognostic studies.The study was conducted at a tertiary referral cardiac hospital; as a result high prevalence of severe heart failure symptoms (20%) and LV outflow obstruction (50%) were observed.The small number of HC patients is a weakness of our study, and also we can not exclude the possibility that some patients may develop advanced symptoms of heart failure later in life. NYHA classification, as a subjective measurement of functional disability, may not always reflect functional status accurately in HC patients, but in previous studies, metabolic stress testing in a large HC cohort showed peak oxygen consumption to be significantly related to NYHA class .For HC patients, LMSa, EDt and LV outflow obstruction are independent predictors of heart failure symptoms. These findings suggest that diastolic dysfunction determined with EDt, occult systolic dysfunction which is detected with tissue Doppler analysis, and afterload increase as result of LV outflow obstruction may be the main echocardiographic factors affecting symptomatic status in HC patients with sinus rhythm and normal systolic function.The authors declare that they have no competing interests.FB carried out the echocardiographic studies, participated in the design of the study and drafted the manuscript. GK carried out the carried out the echocardiographic studies and drafted the manuscript. MD participated in the design of the study and performed the statistical analysis. BM conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.Written informed consent was obtained from all patients for publication of manuscript. Copies of the written consents are available for review by the Editor-in-Chief of this journal.