Diastolic dysfunction precedes systolic dysfunction in patients with coronary artery disease. The aim of the study was to evaluate the effects of left ventricular (LV) wall motion abnormality (WMA) on diastolic LV and right ventricular (RV) function at rest and after stress.Fifty-nine subjects, 15 with LV-WMA  and 44 without , underwent dobutamine stress echocardiography (DSE) studies, in addition to evaluation of LV and RV diastolic function before and after DSE.Resting mitral flow parameters were similar. DSE increased peak A-wave velocities in both groups, and mitral color slope only in normal subjects. After DSE, E-wave peak velocities and mitral color slope were higher in normal subjects, P < 0.05. At rest and after DSE systolic and diastolic pulmonary vein velocities were similar in both groups; however, DSE increased these velocities only in normal subjects, P < 0.05. Regional E-wave peak velocities of LV were higher at rest in normal subjects, P < 0.05. Both LV and RV, regional peak E-wave velocities were not affected by DSE. After DSE, regional A-wave peak velocities increased in all (P < 0.01), except at the lateral region (P = 0.07). DSE increased trans-tricuspid velocities in both groups, P < 0.05. Resting A-wave velocities were higher in normal subjects, P < 0.01.Global LV early diastolic filling parameters were not affected by LV-WMA at rest. LV-WMA blunted the response after stress. RV E-wave velocities increased after DSE, and were not affected by LV-WMA. LV-WMA reduced regional LV-E’ velocities at rest but not the reserve. A-wave velocities were not affected by WMA and increased after DSE. Myocardial fibers of both ventricles have similar helical architecture and are linked to each other , 2. DynaLongitudinal ventricular systolic dysfunction precedes radial abnormalities . AccordiFifty-nine patients without the exclusion criteria, 29 women, aged 60.3 ± 13.4 years, were prospectively evaluated for the presence of coronary artery disease. Fifteen of the subjects  had wall motion abnormality (WMA) at rest, and 44 had no WMA at rest . Exclusion criteria included presence of pulmonary disease, right heart disease, valvular heart disease, atrial fibrillation or other rhythm disturbances and acute coronary syndrome within the last 3 months were not included. All subjects underwent DSE studies using the usual protocol, and measurement of mitral and tricuspid diastolic annular velocities before and immediately after the stress study.The protocol of dobutamine infusion consisted of 3 min stages for each dose, staring with 5 µg/kg/min and increasing to 10, 20, 30 and 40 µg/kg/min. If end-points did not occur or 85% of the age adjusted heart rate was not achieved, 0.25 mg atropine was injected every 2 min up to 1 mg or until the target heart rate was achieved. Blood pressure and 12-lead electrocardiograms were recorded at rest and throughout the DSE study. Horizontal or down-sloping > 1 mm ST-segment depression at 0.06 s after the J point were considered as evidence for myocardial ischemia.Images were obtained while the patients in the left lateral decubitus position. A standard commercial Siemens, Acuson Sequoia echocardiography system, California, equipped with 3.5 MHz transducers was used. All patients had complete Doppler echocardiographic studies before DSE studies. Parasternal long axis and short axis as well as apical four-chamber and two-chamber views were recorded at rest, low dose dobutamine infusion, peak exercise and in the recovery period. Digital images were stored on magneto-optic discs for later off-line analysis. In addition, super VHS videotape recordings were performed throughout the studies.Segmental LV wall motion analysis was performed using 16-segment model. Regional wall motion and segmental score was estimated as normal = 1, hypokinetic = 2, akinetic = 3 or dyskinetic = 4. New or worsening segmental WMA was considered as ischemic response. Ischemic response (I) was identified when wall motion decreased by at least one grade in two adjacent segments or wall motion decreased by at least two grades in one segment, otherwise no ischemia, or normal response (N) was diagnosed. Wall motion score index (WMSI) was calculated as in The sample volume of the pulsed wave Doppler was placed at the tips of mitral and tricuspid valves to record LV and RV inflow velocities. At rest, easily discernible E and A wave velocities were recorded in all subjects. After DSE studies, recording of ventricular inflow velocities was delayed until the earliest separation of E and A waves was observed at heart rates 108 ± 2 bpm as previously reported [Pulmonary venous peak systolic and diastolic velocities were measured form the apical four-chamber view and averaged from three consecutive beats.The apical four-chamber, two-chamber and three-chamber views were used to assess the longitudinal diastolic velocities of the mitral annulus. The sample volume of the pulsed wave Doppler was located at the mitral annulus and recording was performed from the septal, lateral, anterior, inferior and posterior portions of the annulus. In addition, Doppler sampling from the proximal anteroseptal segment was performed. Tricuspid diastolic annular velocities were recorded from the lateral border from the apical four-chamber view. Annular Doppler velocities were recorded on videotape for off-line analysis. Measurements were averaged from three consecutive beats.t-test assuming unequal variances was used to compare the normal and abnormal groups, while paired t-test was performed to compare the parameters before and after DSE in both groups; P < 0.05 was considered significant.Statistical analyses were conducted using SPSS software version 13 . Mean values and standard deviation of the six annular mitral and the lateral tricuspid annular longitudinal diastolic velocities were calculated for all. Student’s All subjects underwent DSE studies safely and uneventfully. Heart rate increased from 62.4 ± 9.9 bpm to 133 ± 14.4 bpm. Systolic blood pressure increased from 138 ± 7 mm Hg to 162 ± 9 mm Hg. In the normal group, heart rate increased from 70.7 ± 10 bpm to 138 ± 11.8 bpm, P < 0.00001, and in the abnormal group, heart rate increased from 74.2 ± 17.6 bpm to 130.9 ± 15.6 bpm, P < 0.00001. Heart rate was similar between groups both at rest and after DSE studies. Systolic blood pressure increased from 138 ± 7 mm Hg to 162 ± 9 mm Hg, P < 0.0001, in all subjects without significant inter-group difference.In 26 subjects, WMSI was 1 at rest and did not change after DSE, while in 18 subjects WMSI was 1 at rest and increased to 1.12 ± 0.14 after stress. In 15 subjects, WMSI at rest was 1.36 ± 0.34 and increased to 1.47 ± 0.32 after DSE.At rest, no significant difference was found in trans-mitral filling pulsed-wave Doppler velocity parameters, mitral color slope or pulsed-wave pulmonary venous velocities between groups with and without LV-WMA .In both groups, after DSE studies, peak E-wave velocity did not increase significantly. Mitral early diastolic color Doppler slope increased only in the normal group . Peak laAfter DSE studies, the normal group had faster early diastolic LV filling with higher peak E-wave velocity, peak E/A velocity ratio and faster early diastolic mitral color Doppler slope compared to the abnormal group . PulmonaAnnular E and A velocities were discernable in all subjects both at rest and after DSE studies.At rest, LV tissue-Doppler early diastolic E’ velocities were higher in all proximal regions in the normal group compared to the abnormal group . Late diDSE test significantly increased A’ velocities in all regions, while E’ velocities did not change . After DAfter DSE test, only in the proximal inferior LV segment, E’ was higher in the normal group than in the abnormal group, while all the other velocities and velocity ratios were similar in both groups .At rest trans-tricuspid late diastolic A-wave peak velocity was higher in the normal group than in the abnormal group, while the other parameters were similar .DSE test increased peak E-wave and A-wave tricuspid velocities in both groups; however, E/A velocity ratio decreased only in the normal group . While AAfter DSE test, no difference in any parameter was observed between the groups .Global early diastolic LV filling velocities at rest, as assessed by mitral E-wave velocity, mitral color slope and pulmonary venous velocities, were not affected by the presence of LV-WMA. On the other hand, regional early diastolic velocities by tissue Doppler were lower in the presence of LV-WMA. Global LV early diastolic E-wave peak velocity after DSE test was higher in the absence of WMA. In the normal group, a marked increase in global early LV filling parameters and pulmonary venous return were observed after DSE test, which may indicate a better diastolic reserve and enhanced LV diastolic relaxation. Late diastolic global and regional A-wave velocities increased after DSE test and were not affected by LV-WMA both at rest and after stress. The ratio of mitral E/E’, as an estimate of left atrial pressure , was simEarly diastolic global RV filling peak E-wave velocity increased significantly after DSE test and was similar in both groups at rest and after stress. Regional RV early filling E’-wave velocity by tissue Doppler was similar in both groups and did not change after stress. The RV E/E’ ratio, an indicator of right atrial pressure , mildly It is expected to find an increase in late diastolic A-wave mitral velocity in association with the increase in heart rate with dobuatmine as previously reported . The incWhile global LV filling was similar at rest in both groups, regional early diastolic LV filling by tissue Doppler was more sensitive and distinguished the normal group by having faster early diastolic E-wave tissue Doppler velocities. This difference in regional early diastolic velocities was translated into the better global early diastolic LV filling reserve in normal group. Similar to global LV late diastolic A-wave velocity, the increase in heart rate with dobuatmine resulted in higher regional tissue Doppler late diastolic A-wave velocities in both groups irrespective of the presence of LV-WMA. After DSE test, neither E or A regional tissue Doppler velocities, nor the ration of E/E’ or A/A’ distinguished between the groups.The presence of LV-WMA did not affect RV early diastolic filling. Thus, with the increase in stroke volume after dobuatmine, E-wave tricuspid valve velocities increased in both groups. Tricuspid valve early diastolic E-wave velocity was similar in both groups both at rest and after stress. Higher heart rates with dobuatmine, as expected, increased A-wave tricuspid valve velocity without significant intergroup difference. Regional early diastolic E-wave velocity and E/E’ ratio were similar in both groups and did not change with dobutamine.The structure of the myocardium of RV and LV is somewhat different. Thus, contrary to the LV, which is composed of three myocardial fiber layers - superficial obliquely directed fibers, middle circumferentially directed fibers and deep inner layer with longitudinal fibers, the RV wall is composed of two myofiber layers . The dirGlobal LV relaxation as evaluated by early diastolic global LV filling parameters was not affected by LV-WMA at rest; however, LV-WMA abolished their reserve. RV E-wave velocities increased after DSE test, and were not affected by LV-WMA. LV-WMA reduced regional LV annular E’ velocities at rest but did not affect their reserve. Late diastolic A-wave velocities were not affected by WMA and increased after DSE test.At high heart rates, E and A waves through the atrioventricular valves merge together and it is not possible to identify these waves separately. Therefore, these waves were recorded when the heart rate decreased below 110 bpm . Tissue


Iron quantification using T2* has become a routine non-invasive procedure for assessment of myocardium and liver in patients with regular transfusions. Cardiologists and cardiovascular radiologists are progressively measuring iron overload in the liver associated with myocardial overload. It is currently unknown if potential interference of high fat content in the liver may result in discrepant iron estimations. We sought to evaluate whether the use of regular T2* sequences would be confounded by fat in comparison to a commercial software with fat-water separation.-TE/T2* with nonlinear fit and truncation to correct for high iron levels. For the commercial sequence, automatic R2* and fat-fraction maps were created automatically by the software and a ROI was traced on these maps to obtain R2* (1/T2*) and fat fraction (FF) percentage values. Patients were divided according to FF  and liver iron concentration . A comparison of T2* values using both softwares was performed and analyzed according to fat and iron concentrations.Twenty-six patients with clinical indication for liver and myocardial iron assessment were studied using a 1.5T scanner (GE Optima 450). In all patients, an axial image of the liver was acquired using a multi-echo single breath-hold GRE sequence with 10 TEs and fat saturation followed by an image using a three-dimensional volumetric imaging sequence  with six echo times. For the T2* GRE sequence, a region of interest (ROI) was drawn through the right lobe of the liver and the mean signal intensity for each echo time used to fit the T2* decay curve with the formula SI = KeThe mean age of participants was 44 ± 14.2 years with 73% males. The fat-water separated results yielded a mean T2* of 17.1 ± 8.0 ms versus GRE-T2* of 15.6 ± 7.0 ms (P=0.01) - Figure With traditional GRE-T2* sequences, fat content of the liver will not significantly affect usual T2* measurements in patient with either low fat content (FF < 10%) or abnormal iron stores (T2* < 15.4 ms). In patients with normal liver iron concentrations and high fat content, GRE-T2* underestimates the liver T2* values.


There are limited data reported on the myocardial ECV in an essential hypertension patient population. The purpose of this study was to determine whether extracellular volume fraction (ECV) quantification by cardiac magnetic resonance (CMR) can demonstrate left ventricle (LV) abnormalities in a cohort of consecutive hypertension (HTN) patients, and to investigate the relationship between ECV and global LV function and LV remodelling.t test, and multiple regressions.ECV quantification with cardiac MR imaging was prospectively performed in 134 consecutive HTN patients and 97 healthy subjects. The HTN patients were separated into two subgroups according to LGE present or not. Individual and regional ECV were compared to the regions on LGE images using a 17-segment model. Statistical comparisons of LV global functional parameters, and ECV were carried out using the Pearson correlation, Student P<0.001), respectively. The differences of ECV reached statistical significance among the regions of LGE area, LGE-Peri area, LGE remote area and the normal area of the control group in LGE positive subgroup. Global ECV significantly correlated with LVEF  and LV hypertrophy .In HTN group, 70.1 %( 94/134) was LGE negative and 29.9% (40/134) was LGE positive. The average ECV in healthy controls and LGE negative patients were 26.9 ± 2.67 % and 28.5 ± 2.9% (ECV imaging by cardiac MR imaging can identify LV abnormalities at an early stage in HTN patients without LGE. These abnormalities may reflect increase in diffuse myocardial fibrosis and are associated with LV remodelling.


Radiation-induced parotid damage is a common complication in patients with nasopharyngeal carcinoma (NPC) treated with radiotherapy to head and neck region, which severely reduce the life quality of those patients. The aim of this study was to early evaluate the changes of irradiated parotid glands with T2 mapping and mDIXON Quant imaging.Forty-one patients with NPC underwent conventional magnetic resonance imaging for nasopharynx and neck, and T2 mapping and mDIXON Quant imaging for bilateral parotid glands within 2 weeks before radiotherapy (pre-RT), 5 weeks after the beginning of radiotherapy (mid-RT), and 4 weeks after radiotherapy (post-RT). Parotid volume, T2 values, fat fraction (FF) values, and mean radiation dose were recorded and analyzed.P = 0.027). Multiple linear regression analysis showed that parotid T2 value  and FF value  negatively correlated with parotid volume, while parotid T2 value positively correlated with MR scan time point  significantly. Parotid T2 and FF values showed excellent reproducibility .From pre-RT to mid-RT, parotid volume decreased , while parotid T2 and FF values increased  significantly. From mid-RT to post-RT, parotid T2 value continuously increased , but parotid FF value decreased  significantly. Change rate of parotid T2 value significantly correlated with parotid atrophy rate from pre-RT to post-RT (r = 0.313, T2 mapping and mDIXON Quant imaging is useful for noninvasive evaluation of radiation-induced parotid damage. Patients with nasopharyngeal carcinoma (NPC) always suffer from radiation-induced xerostomia, dysphagia, and even dental caries, which severely reduce their life quality . In receDegree of xerostomia can be clinically evaluated with Radiation Therapy Oncology Group (RTOG) criteria , which mPrevious studies confirmed the glandular edema and fatty replacement in irradiated parotid glands , 11. TisTherefore, the primary purpose of this study was to early evaluate the dynamic changes of radiation-induced parotid damage with T2 mapping and mDIXON Quant imaging. Correlations between parotid T2 or FF values and parotid atrophy rate or mean radiation dose were also investigated.n = 0); (2) with parotid gland diseases, such as Sjögren’s syndrome (n = 1); (3) with MR contraindications, such as cardiac pacemaker or cochlear implants (n = 0); (4) unable to accomplish the whole course of MR follow-ups (n = 7); (5) with geometric distortion or physiologic motion on MR images (n = 2). Hence, 41 patients with NPC served as our study cohort .This study was approved by the institutional review board. After providing written informed consents, 51 patients was enrolled prospectively. The inclusion criteria were: (1) with a biopsy confirmed diagnosis of NPC; (2) scheduled to undergo IMRT; (3) willing to receive MR evaluation and follow-ups in our hospital. The exclusion criteria included: (1) with a history of radiotherapy to the head and neck region . The accumulated mean radiation dose of parotid gland at mid-RT (20.4 ± 2.7 Gy) or post-RT (29.2 ± 3.3 Gy) was also calculated. The mean radiation dose of parotid gland in each patient was under the constraint in our hospital (30–50 Gy for 50% of parotid volume).The chemoradiotherapy scheme for NPC patients has been described in a previous article . All patOne hour before MR scanning, the xerostomia degree of patients was assessed by a radiation oncologist  according to RTOG criteria . The xerAll patients was required to fast for at least 2 h before MR scanning. A 3.0-T MR scanner  with a 16-channel head&neck phased-array coil was used. 32-channel Torso coil was added for mDIXON Quant imaging. The patient’s position was head first and supine. Among 41 patients, 22 patients underwent conventional MR and T2 mapping imaging (from May 2016 to January 2017), 6 patients underwent conventional MR, T2 mapping, and mDIXON Quant imaging (from January 2017 to March 2017), and the remaining 13 patients underwent conventional MR and mDIXON Quant imaging (from March 2017 to July 2017), respectively. The conventional MR imaging included fat-saturated T2-weighted imaging in coronal and transverse planes, T1-weighted imaging in coronal, sagittal, and transverse planes, and contrast enhanced fat-saturated T1-weighted imaging in coronal, sagittal, and transverse planes.T1-weighted imaging was obtained by using turbo spin-echo (TSE) sequence, whose parameters were as follows: repetition time (TR) / echo time (TE) = 400–675 msec / 18 msec, field of view (FOV) = 22 cm, voxel size = 0.8 mm × 0.92 mm, matrix = 276 × 215, slice thickness = 5 mm, slices = 38, number of signals averaged (NSA) = 2. The scan duration was 2 min 27 s.T2 mapping was obtained by using multi-slice multi-echo TSE sequence, whose parameters were as follows: TR / TE1 = 2109 msec / 17 msec, delta TE = 17 msec, echoes = 5, FOV = 22 cm, voxel size = 1.8 mm × 2.4 mm, matrix = 124 × 90, slice thickness = 4 mm, slices = 20, NSA = 1. The scan duration was 33 s.mDIXON Quant imaging was obtained by using 3D fast field echo (FFE) sequence, whose parameters were as follows: TR / TE1 = 10 msec / 1.47 msec, delta TE = 1.2 msec, echoes = 6, FOV = 25 cm × 24 cm, voxel size = 1.2 mm × 1.2 mm, matrix = 208 × 201, slice thickness = 2.5 mm, slices = 64, NSA = 2. The scan duration was 2 min 7 s. A low flip angle of only 3° was applied to limit the T1 bias, and 6 echoes was used to correct for T2* effects.Measurements of MR parameters were performed by two radiologists  independently. Both of them were blinded to the clinical data of patients. Parotid volume, T2, and FF values were measured on a workstation .V = (Vpre − Vmid/post) / Vpre × 100%, where RV is the atrophy rate of parotid gland from pre-RT to mid-RT or post-RT, and Vpre and Vmid/post are parotid volume at pre-RT, mid-RT, and post-RT, respectively.Each slice area of parotid gland was measured on T1-weighted image. Parotid volume was calculated by using the following equation: V = Σ S푖 × (ST + SG), where V is parotid volume, S푖 is each slice area, ST is slice thickness, and SG is slice gap. The atrophy rate of parotid gland was calculated by using the following equation: RPara = (Paramid/post – Parapre)/Parapre × 100%, where RPara is the change rates of parotid T2 or FF values from pre-RT to mid-RT or post-RT, and Parapre and Paramid/post are the T2 or FF value of parotid gland at pre-RT, mid-RT, and post-RT, respectively.After acquisition of T2 mapping and mDIXON Quant sequence, T2 and FF maps were automatically calculated. The regions of interest (ROIs) were drawn within the largest three slices of parotid gland on T2-wighted image (T2 mapping sequence with TE = 51 msec) and FF map to include as much parotid parenchyma as possible excluding visible parotid ducts and retromandibular veins. The ROIs on T2-wighted image were manually copied to the corresponding T2 map to calculate T2 value. The T2 and FF values were defined as the averaged value of the largest three slices. The change rates of parotid T2 and FF values were calculated by using the following equation: RThe final T2 and FF values of parotid gland were recorded as the averaged value of the two radiologists’ measurements. With an interval of 12 weeks, parotid T2 and FF values were re-measured by the second radiologist to assess the intra-oberver reproducibility.t test with Bonferroni correction. Two independent-samples t test was used to compare the change rates of parotid T2 or FF value between men and women. Pearson’s correlation test was used to detect correlations between the change rates of T2 or FF value and parotid atrophy rate, mean radiation dose, or age. Correlations among parotid T2 or FF value, parotid volume, and MR scan time point was detected by multiple linear regression analysis. Intraclass correlation coefficient (ICC) was used to evaluate the reproducibility of parotid T2 and FF values measurements. All statistical analyses were performed using SPSS 16.0 software . A P value < 0.017 for paired sample t test with Bonferroni correction and a P value < 0.05 for other statistical analyses indicated a statistical significance.Continuous data were shown as mean ± standard deviation. The dynamic changes of parotid volume, T2 and FF values were analyzed by using paired sample The dynamic changes of parotid volume, T2 and FF values are shown in Table From pre-RT to mid-RT, parotid volume decreased significantly . However, no significant difference was found in parotid volume from mid-RT to post-RT. Hence, the overall atrophy rate of parotid volume from pre-RT to post-RT was 27.0 ± 10.8%.From pre-RT to mid-RT, parotid T2 value increased significantly , and continued to increase significantly from mid-RT to post-RT . Hence, the overall change rate of parotid T2 value from pre-RT to post-RT was 10.8 ± 10.0%.From pre-RT to mid-RT, parotid FF value increased significantly , and then decreased significantly from mid-RT to post-RT . Hence, parotid FF value did not change significantly from pre-RT to post-RT.P > 0.05).From pre-RT to mid-RT or post-RT, no significant differences of the change rates of parotid T2 or FF value were found between men  and women  .As shown in Table P = 0.001), but positively correlated with MR scan time point  significantly. Parotid FF value negatively correlated with parotid volume significantly , yet did not correlate with MR scan time point .Multiple linear regression analysis showed that parotid T2 value negatively correlated with parotid volume  and 0.935  for T2 value, and 0.992  and 0.984  for FF value, respectively.Parotid volume decreased significantly after radiotherapy with an atrophy rate of 27%, which might be due to the loss of acinar cells . HouweliP = 0.023 for ADC; r = 0.357 and P = 0.018 for ADClow; r = 0.378 and P = 0.012 for f) [Parotid T2 value continuously increased during radiotherapy, which can be explained by the continuous aggravation of tissue edema . Houweli2 for f) . Hence, The pre-RT parotid FF value of NPC patients  was approximately 38.2% in this study. Kise et al. reported a mean parotid FF value of 29.4% in healthy volunteers  at 3.0-T MR scanner, which was slightly lower than ours . Chang eParotid FF value first increased and then decreased during radiotherapy. Multiple linear regression analysis revealed that early increase of FF value was mainly due to parotid atrophy from pre-RT to mid-RT. From mid-RT to post-RT, parotid volume remained unchanged, while glandular edema continuously aggravated. The FF value reflects the relative proton density ratio between fat signal and the sum of fat and water signals , 21, whiParotid T2 and FF values showed excellent intra- and inter-observer reproducibility. Serai et al. reported an ICC of 0.992 for parotid FF value in healthy volunteers obtained from mDIXON Quant imaging at 3.0-T MR scanner , which wOur study had several limitations. First, the sample size was relatively small, yet still larger than other investigations on radiation-induced parotid damage with MR imaging , 19. SecT2 mapping and mDIXON Quant imaging provided pathophysiological information of parotid gland during radiotherapy, which could serve as an objective and quantitative modality in evaluating early radiation-induced parotid damage and facilitate a timely adjustment of treatment scheme to alleviate the damage of parotid glands.


The systemic right ventricle (RV) in patients with hypoplastic left heart syndrome (HLHS) is prone to failure. The complex geometry and contraction pattern of the systemic RV makes identification of patients at risk for failure challenging, especially in the light of radical changes in loading conditions during staged palliation. MRI allows for accurate quantification of cardiac volumes and provides assessment of the whole heart without restrictions in imaging planes. Recent advances in cardiac MRI analysis software allows for quantification of regional deformation from conventional balanced steady state free precession cine images.We sought to investigate changes in ventricular function before and after the hemi-Fontan (HF).25 HLHS patients underwent cardiac MRI both before HF and before total cavopulmonary connection (TCPC). Global and regional strain parameters, mechanical dyssynchrony index (MDI) and cardiac volumes were obtained from all exams and compared pre- and post-HF. Circumferential, longitudinal and radial strain, strain rate, type of contraction pattern and MDI were correlated with volumetric indices and global systolic function in order to investigate possible mechanisms of RV dysfunction.p<.05), with an increase in RV ejection fraction (EF) (p<.01). RV longitudinal strain did not significantly change from pre-HF to pre-TCPC whereas circumferential and radial strain increased resulting in a more circumferential rather than longitudinal dominant contraction pattern . Mechanical contraction became more synchronous; MDI pre-HF 11.4%, pre-TCPC 7.2% (p<.01). Both changes in global radial and circumferential strain correlated with EF  whereas longitudinal strain did not. The change in contraction pattern from longitudinal to circumferential dominant contraction was not correlated with a decline in ventricular EF . Mechanical dyssynchrony index decreased from pre-HF to pre-TCPC assessment but this was not correlated to an increase in EF.The volume unloading during HF surgery resulted in a decrease in end-diastolic and end systolic volumes  correlate with changes of global ventricular function in children with HLHS undergoing staged palliation. However, changes in longitudinal strain and mechanical dyssynchrony do not seem to correlate with EF. Serial assessment of circumferential contraction indices might be useful in the identification systemic right ventricular adaptation in response to staged surgical palliation in HLHS.


Myocardial perfusion imaging during hyperaemic stress is commonly used to detect coronary artery disease. The aim of this study was to investigate the relationship between left ventricular global longitudinal strain (GLS), strain rate (GLSR), myocardial early (E’) and late diastolic velocities (A’) with adenosine stress first-pass perfusion cardiovascular magnetic resonance (CMR) imaging.p-value = 0.02), E’ , GLSR  and stress GLS  were significantly reduced when compared with patients with no perfusion defects. Stress GLS was the strongest independent predictor of perfusion defects . A threshold of −19.8% for stress GLS demonstrated 78% sensitivity and 73% specificity for the presence of hyperaemia-induced perfusion defects.44 patients met the inclusion criteria and underwent CMR imaging. The CMR imaging protocol included: rest/stress horizontal long-axis (HLA) cine, rest/stress first-pass adenosine perfusion and late gadolinium enhancement imaging. Rest and stress HLA cine CMR images were analysed using feature-tracking software for the assessment of myocardial deformation. The presence of perfusion defects was scored on a binomial scale. In patients with hyperaemia-induced perfusion defects, rest global longitudinal strain GLS  contains supplementary material, which is available to authorized users. Althougiography .Fig. 1IlMyocardial strain imaging allows quantification of subtle changes of LV function that typically precede a reduction in LV ejection fraction (EF) . MyocardTherefore, the purpose of this study was to investigate the relationship between left ventricular global longitudinal strain (GLS), strain rate (GLSR), myocardial early (E’) and late diastolic velocities (A’) with adenosine stress first-pass perfusion CMR and determine which strain parameter is most strongly associated with the presence of a perfusion defect.2, non-ischaemic cardiomyopathy or any contraindication to CMR imaging. All patients gave written informed consent for their data to be used in this study.This was a prospective-cohort study of patients presenting to the rapid access chest pain clinic in a single tertiary cardiology centre, who were referred on clinical grounds for a stress CMR study for the evaluation of suspected CAD. Exclusion criteria were: estimated glomerular filtration rate <30 ml/min/1.73 mThe study protocol was approved by the local research ethics committee. The present study complied with the Declaration of Helsinki and all patients gave written informed consent.CMR protocol included: rest/stress horizontal long-axis (HLA) cine, rest/stress first-pass adenosine perfusion and late gadolinium enhancement imaging. CMR protocol is detailed in the online Supplementary File 1.CMR images were anonymised, which included the removal of dates of acquisition and any identifiable data. Cines, perfusion and LGE images were blindly evaluated offline using commercially available software  by one observer (RA). Left ventricular volumes and ejection fraction (EF) were analysed from short-axis cine images using standard methods . InfarctStrain analysis was performed using a cvi42 (v5.1) feature tracking (FT) module in a semi-automated manner . Stress global longitudinal strain parameters were derived from HLA cines only as no VLA images were acquired in order to minimise the duration of adenosine infusion. Peak GLS, GLSR, E’ and A’ were recorded per case.Perfusion images were independently analysed by two experts in perfusion analysis with greater than 3‑years’ experience each (TAM and DPR). Each expert reported on the presence of inducible stress perfusion defects that were not present on rest perfusion images and with no corresponding scar on LGE images. In case of disagreement between the two observers, a third independent expert analysed the images, and a discussion of all observers took place to reach a unanimous decision (PG). Studies in which a unanimous decision could not be reached were excluded. On stress perfusion imaging, an area of decreased signal intensity when compared with remote myocardium and the presence of an endocardial to epicardial perfusion gradient were classified as a perfusion defect .Statistical analysis was performed using IBM SPSS Statistics 21.0. Continuous variables were expressed, as mean ± SD. Normality of quantitative data was established using the Shapiro-Wilk test. Demographic comparisons between two groups of patients (with and without perfusion defect) were performed with an independent samples t‑test. The rest of the statistical methods are detailed in the online Supplementary File 1.A total of 50 patients were recruited; 4 patients had equivocal perfusion results, resulting in exclusion from the study and 2 patients were claustrophobic. From the remaining 44 patients, 22 patients had an inducible perfusion defect, and 22 patients had no inducible perfusion defect. The two independent graders agreed on the categorisation of all cases with no arbitration required. The demographics, clinical data and baseline CMR results are shown in Tab. All cine images were of adequate quality for FT analysis. Fig. p-value = 0.05). Other strain parameters, GLSR , E’ , A  did not show significant changes between rest and stress.The absolute change in rest versus stress GLS demonstrated an increase in GLS in patients without perfusion defects but a reduction in GLS at stress in patients with a perfusion defect  and stress GLS . However, patients with previous myocardial infarction did not show more inducible perfusion defects than those without previous myocardial infarction (odds ratio (OR) 0.38, p-value = 0.13).Patients with previous myocardial infarction on LGE imaging had lower rest GLS  (Online Supplementary File 2). The logistic regression strain model was independently associated with presence of perfusion defect  when compared with other individual myocardial strain parameters.In the logistic regression analysis, stress GLS demonstrated the best independent association with the presence of a perfusion defect of the parameters tested  at peak myocardial hyperaemia, GLS is reduced in patients with inducible perfusion defects; 2) stress GLS is most strongly associated with the presence of a perfusion defect; and 3) a cut-off value of −19.8% for stress GLS demonstrates 77% sensitivity and 73% specificity for the presence of a perfusion defect.Myocardial ischaemia initially affects the endocardium and progresses to the sub-epicardial layers in a ‘wave front’ manner . High reIn patients with evidence of myocardial infarction on LGE imaging, rest GLS, GLSR and E’ were also correlated with the presence of perfusion defects, however, these resting strain parameters did not discriminate between patients with and without perfusion defects in the absence of previous myocardial infarction. Like ischaemia, myocardial infarction predominantly affects the endocardial layer and a longitudinal myocardial strain and a reduction in resting myocardial deformation can therefore be expected. The correlation with the presence of an inducible perfusion defect is likely to be caused by co-existing CAD in other territories or peri-infarct ischaemia, both of which were common in the present population in patients with prior MI. However, resting strain parameters are not reliable markers of inducible ischaemia as shown by the lack of correlation with perfusion defects in patients without myocardial infarction.p > 0.05). As the strain model requires multiple strain analyses, the use of stress GLS alone may be a more practical approach for clinical studies.A strain model comprising of rest GLS, GLSR, E’ and stress GLS performed slightly better in this study than stress GLS alone in linear regression Tab. , but wasPrevious echocardiographic studies have reported findings that are consistent with our observations. Liang et al. found that rest peak systolic strain rate  and peak early diastolic strain rate (E’ in our study) were significantly lower in patients with significant CAD (>70% stenosis) than controls . Our stuThe sample size of this proof-of-concept study is small, although large enough to detect statistically significant differences on logistic regression analysis and thus justifying larger studies to investigate this concept further. For practical and conceptual reasons, we did not use coronary stenosis on invasive angiography but perfusion defects on myocardial perfusion CMR as the primary end-point . ContempIn this mechanistic study, at peak myocardial hyperaemic stress, GLS is reduced in the presence of a myocardial perfusion defect, most likely secondary to reduced endocardial blood flow as a result of hyperaemia-induced redistribution of transmural perfusion. Additionally, this study demonstrates the feasibility of adenosine stress myocardial strain CMR which may provide clinically relevant information and justifies further larger studies to investigate the accuracy of using CMR-FT-derived strain to predict the presence of CAD.Detail description of CMR protocol and statistical methodsRegression analysis table


Following the original large-scale randomized trials of aspirin and β-blockade, there have been a number of major advances in pharmacological and mechanical treatments for acute myocardial infarction. Despite this progress, myocardial infarction remains a major global cause of mortality and morbidity, driving a quest for novel treatments in this area. As the understanding of mitochondrial dynamics and the pathophysiology of reperfusion injury has evolved, the last three decades have seen advances in ischemic conditioning, pharmacological and metabolic cardioprotection, as well as biological and stem-cell therapies. The aim of this review is to provide a synopsis of adjunctive cardioprotective and regenerative therapies currently undergoing or entering early clinical trials in the treatment of patients with acute myocardial infarction. Ischemic heart disease remains a leading cause of death worldwide, responsible for an estimated 17.5 million deaths in 2012 [The current management of patients presenting with acute myocardial infarction focuses on antiplatelet and antithrombotic treatment coupled with invasive assessment of coronary anatomy with a view to revascularization where appropriate . PharmacA literature search was performed by two authors using PubMed and ClinicalTrials.gov using the following key words: ‘novel therapies’, ‘regenerative therapies’, ‘myocardial infarction’, ‘reperfusion injury’, ‘ischemic conditioning’, ‘pharmacological conditioning’ and ‘cardioprotection’ to identify relevant ongoing or recent clinical trials and systematic reviews on cardioprotective and regenerative therapies for acute myocardial infarction undergoing current or recent clinical trial . We limiWhile restoration of myocardial perfusion remains the cornerstone of treatment for acute coronary occlusion, reducing the insult caused by the ensuing reperfusion injury has attracted significant interest in recent years. Myocardial reperfusion injury describes the damage to or death of vulnerable myocytes that occurs as a result of restoration of blood flow and has been seen following thrombolysis, percutaneous coronary intervention (PCI), coronary artery bypass grafting and cardiac transplantation . CentralOur understanding of mitochondrial dynamics has advanced significantly in recent years, notably of their role in the regulation of cell death. Independent of mode, cell death is intrinsically linked to mitochondrial dynamics through regulation of mitochondrial membrane permeabilization which, once induced, initiates a rapid and irreversible cascade of enzymatic interactions that ultimately leads to organized cell destruction . Mitochoet al. [The phenomenon of ischemic preconditioning, administration of periods of short-lived ischemia prior to a more prolonged ischemic insult, was first demonstrated almost 30 years ago by Murry et al.  who obseet al. . The preet al. ,15.The invasive nature and temporal requirements of the local preconditioning stimulus relative to the ischemia-reperfusion insult have limited the applicability of local IPC in the setting of acute myocardial infarction. Consequently, attention has focused on remote IPC (rIPC), where tissues other than the heart are exposed to ischemia protocols, with subsequent signaling pathways resulting in a reduction in myocardial reperfusion injury. This phenomenon was first demonstrated within the canine coronary arterial tree where transient occlusion of circumflex artery prior to induction of ischemia reperfusion injury in the left anterior descending artery in canine models resulted in a significant reduction in infarct size (6 vs 16% in controls) . In the For obvious reasons, cross-clamping of the aorta would be impractical in patients presenting with acute myocardial infarction. As a surrogate, transient limb ischemia induced by inflation of a blood pressure cuff to suprasystolic pressure has also been shown to be sufficient to induce myocardial protection in patients exposed to ischemia-reperfusion injury. Three recent meta-analyses of rIPC using transient limb ischemia as the stimulus  . Bøtker et al.  randomiz [et al.  randomiz [et al. . Additio [et al.  will addet al. in 2003 utilizing a canine artery ligation model, where administration of three cycles of 30 s of reperfusion and reocclusion immediately following prolonged coronary artery occlusion was found to be as effective as ischemic preconditioning at attenuating myocardial reperfusion injury [Ischemic postconditioning, or slow reperfusion, was first demonstrated by Zhao n injury . The then injury  and, as n injury .et al. found no net cardioprotective effect from postconditioning, with small sample sizes biasing outcomes of left ventricular ejection fraction [Attempts to translate the experimental benefits of postconditioning into the clinical arena have yielded mixed results. An early prospective multicenter trial randomized patients with acute STEMI to primary PCI alone versus primary PCI followed by intermittent coronary artery occlusions (postconditioning) . The autfraction . Methodofraction .A multitude of pharmacological approaches have been developed to reduce the adverse impact of reperfusion injury. A drug which can be administered intravenously to effectively confer postischemic conditioning offers an attractively practical therapeutic option in comparison to invasive ischemic preconditioning and biological approaches. Preclinical data have highlighted the importance of oxidative stress and chemokine expression as potential therapeutic targets for pharmacological agents in STEMI . We presThe immunosuppressant drug cyclosporine is well established in clinical use in many inflammatory conditions and post-transplantation. Following on from experimental data demonstrating that cyclosporine A inhibits opening of the mPTP, a small randomized pilot study (n = 58) examined the benefits of cyclosporine A in patients with STEMI . Treatmeet al. [Exenatide is a glucagon-like peptide-1 analog used in the treatment of diabetes mellitus . In addiet al. , infusioet al.  followedet al. . A Phaseet al. ), is ongAdenosine has been shown to induce cardioprotective effects in the setting of myocardial ischemia through a variety of proposed mechanisms including regulation of heart rate, blood pressure and vasodilatation . The AMIPreclinical and early clinical data have demonstrated that nitric oxide has cardioprotective potential by reducing myocardial oxygen demand, increasing coronary blood flow and reducing spasm . The NOMAs the importance of molecular signaling at the mitochondrial membrane in ischemia reperfusion injury has become clearer, research has been directed toward directly regulating mitochondrial function. A number of promising candidate drugs targeting mitochondrial function have emerged from preclinical work to undergo Phase I and II clinical trials. Protein kinase C isoenzyme, widely considered essential in the mechanism of reperfusion preconditioning, was investigated in the PROTECTION-AMI  study, wet al. randomized 569 patients with STEMI undergoing primary PCI to either atrial natriuretic peptide or placebo administered as an infusion over 3 days and reported a 14.7% reduction in infarct size by serum biomarker and an increase in left ventricular ejection fraction at 2–8 weeks postinfarct that was still present at 6–12 months [Atrial natriuretic peptide is a powerful endogenous vasodilator. Kitakaze 2 months . However2 months  and, in 2 months . It has 2 months . These fThe SOLSTICE  study inpost hoc analysis, subjects with a large area of myocardium at risk and no anterograde flow did appear to gain some benefit [The function of the myocardial sodium–hydrogen exchanger in intracellular acid-base regulation has also been implicated in reperfusion injury. Disappointingly, following promise in experimental models, the sodium–hydrogen exchanger inhibitors eniporide and cariporide failed to demonstrate any cardioprotective results although there were no concerning adverse effects ,72. More benefit . There iThe compound, FX06, an endogenous peptide derived from human fibrin, has been investigated in the treatment of STEMI on account of its anti-inflammatory properties . The proBioabsorbable alginate IK-5001 is a polysaccharide polymer produced from brown seaweed that, in the presence of excess ionized calcium present in infarcted myocardium, assembles to form a flexible gel structurally resembling extracellular matrix . In theopost hoc analysis, there was a suggestion of benefit in patients with anterior myocardial infarction [Early clinical work has indicated that induction of early mild therapeutic hypothermia may be associated with a reduction in infarct size in patients with acute STEMI ,78. The farction . One of farction  randomizfarction  study fofarction  trial usThe preclinical finding that hyperbaric oxygen delivery can reduce myocardial ischemia-reperfusion injury led to its clinical investigation in AMIHOT I . HyperoxPressure-controlled intermittent coronary sinus occlusion (PICSO) aims to improve myocardial microvascular perfusion following PCI in patients with anterior STEMI. In theory, by occluding the coronary sinus, arterial wedge pressure will rise, increasing perfusion pressure in the infarcted territory. Evaluated in a small safety and feasibility study of 30 patients with STEMI, PICSO had no effect on myocardial recovery or infarct size evaluated by cardiac MRI when compared with matched historical controls . AlthougRegenerative medicine has generated substantial interest in recent years. The prospect of developing novel treatments for acute myocardial infarction that stimulate angiogenesis, promote myocardial regeneration and prevent left ventricular dysfunction is highly attractive. Multiple strategies have been proposed ranging from the mobilization of endogenous progenitor cells through the administration of targeted growth factors to engraftment of autologous or allogeneic cells . The strThe regenerative potential of multiple cell types and sources is being evaluated. These range from pluripotent stem-cell populations capable of differentiation to multiple cardiac cell types, often derived from embryonic stem cells or induced pluripotent stem cells, to adult stem cells including cardiac progenitor cells (CPC), adipose-derived stem cells and bone marrow-derived cells (BMCs). These cells differ widely in their origin, proliferative potential and degree of maturity. The safety and effectiveness of some of these cell therapies have been studied in clinical trials while others await translation to clinical research .Early studies have assessed the effectiveness of adult stem cells (BMC and adipose-derived cells) that are more readily accessible, but less likely to contribute directly to myocardial regeneration. Use of autologous cells avoids the need for immune suppression and circumvents ethical concerns, but these adult stem cells are lineage-committed and less able to differentiate into cardiac cells compared with pluripotent stem cells that can form functional cardiomyocytes, smooth muscle cells and endothelial cells . While Cet al. defined a putative endothelial progenitor cell, isolated from blood mononuclear cells and thought to arise from the bone marrow, with the potential to home to sites of vascular injury and directly contribute to vascular repair and neovascularization [in vivo, but uncertainty remains as to the origin of their progeny [Over a decade ago, Asahara rization . BMC therization . Our undrization . Despite progeny .A myriad of small Phase I and II clinical trials of cell-based therapies in patients with STEMI, with differences in the cell types used and the mode of delivery, have yielded mixed results. Much of the clinical work to date in cell therapies for myocardial infarction has focused on the intracoronary delivery of BMC therapies, but despite a large amount of endeavor, the promise of regenerative cell-based therapies in the setting of acute myocardial infarction has yet to be realized. Meta-analyses of BMC trials performed up to 2008 consistently confirmed a small but statistically significant increase in left ventricular ejection fraction  of cellIn an effort to explain the marked heterogeneity in reported outcomes with autologous BMC therapies in patients with acute myocardial infarction, the DAMASCENE  investig+ mesenchymal stem cells [Mesenchymal stem cells, initially described in bone marrow, have wide differentiation potential and broad tissue distribution . Phase Iem cells . In a reCPCs are resident in adult cardiac tissue and have been evaluated in patients with ischemic cardiomyopathy. There is no consensus as to the optimal method to define these cells, but the surface expression of c-kit (stem-cell factor) provides an opportunity to isolate putative CPC populations from the human heart. The SCIPIO trial  enrolledAs is the case with the type and timing of administration of stem-cell products, optimal dosing and route of administration have yet to be established and this may be partly responsible for the inconsistency of the outcomes to date. The pharmacokinetics and dynamics of live cell-based therapies are fluid and complex so have yet to become sufficiently well understood to provide optimal dosing and route of administration; there have been no studies to date that have simultaneously examined both dose and route . The twoet al. explored the reasons for this failure in an animal model designed to specifically assess impact of the drug when given at varying time intervals and would more accurately reflect those of the clinical studies [The role of cytokine-mediated tissue growth at the peri-infarct zone and stimulation of endogenous myocardium in regulation of the response to injury is increasingly well recognized . It is b studies . They fo studies . To dateFollowing a large number of studies in the field over the past two decades, the initial enthusiasm in biological therapies is moderated by the complexity of the molecular processes regulating cellular repair and regeneration. In general, there have been few safety concerns raised by the clinical studies carried out to date. Although tumor formation and ectopic tissue growth were encountered in animal studies , this haEncouraging preclinical data has often garnered great enthusiasm for development of novel therapies in myocardial infarction, but translating these data in to the clinical arena has often proven challenging. The limitation of animal models of myocardial injury with the absence of substrate for cardiovascular disease, plaque rupture, thrombosis and microembolization is well established, and many clinical studies fail to reach statistical power in recruitment with diverse patient demographics and myocardial injury profiles. The use of cardiac MRI as the gold standard of quantifying change in left ventricular ejection fraction is increasingly accepted, although it is conceivable that the more relevant end point is long-term clinical outcomes.Understanding the physiology of cell signaling in myocardial repair continues to evolve with the potential to progress some biological regenerative therapies. Most cells in the body secrete small membrane-bound vesicles, exosomes, which can regulate intercellular microcommunication in both normal and pathological states . ExosomeTreatment with oral P2Y12 inhibitors is central to the current treatment of patients with acute myocardial infarction. While the benefit of P2Y12 inhibition has been largely attributed to their antiplatelet effect, there are emerging preclinical data to suggest a cardioprotective role in the setting of ischemia-reperfusion injury ,130. GivMajor progress has been made in the development and testing of a wide range of therapies to reduce the impact of reperfusion injury in acute myocardial infarction (summarized in Utility of local ischemic conditioning is limited by its invasive nature.Remote ischemic preconditioning has shown reduction in infarct size and improved long-term clinical outcomes; large-scale clinical trials are ongoing.Ischemic postconditioning has yielded mixed results; large-scale trial is ongoing.Cyclosporine A and exenatide are undergoing clinical trial to clarify early negative clinical studies.Promise shown by atrial natriuretic peptide is mitigated by concerns over increased in-hospital mortality.A variety of innovative and novel agents are still undergoing clinical trial.Cooling confers no significant improvement in left ventricular function overall, but may benefit anterior ST-segment elevation myocardial infarctions and reduce incidence of heart failure.Ongoing clinical trial aims to clarify potential benefit from hyperoxemia.The role of coronary sinus devices has yet to be established.A wide variety of stem cells have undergone preclinical and clinical trial.No consensus is reached on optimal administration and dose regimes.Realizing the potential of biological therapies will depend on continued understanding of intermolecular signaling pathways and cellular dynamics.Significant progress has been made in pursuit of effective therapies against myocardial reperfusion injury.Realization of the promise of cellular therapy may be achieved with a better understanding of the cellular mechanisms of myocardial repair.Modification of gene expression may offer a more widely applicable alternative strategy for myocardial regeneration.


Mitral valve regurgitation (MR) causes blood to flow in two directions during contraction of the left ventricle (LV), that is, forward into the aorta and backward into the left atrium (LA). In aortic valve regurgitation (AR), leakage occurs from the aorta into the LV during diastole. Our objective is to analyze the contribution of a left ventricular assist device (LVAD) to MR and AR for the following two different cannulation sites: from the LA to the aorta (LAAO) and from the LV to the aorta (LVAO). Using a computational method, we simulated three ventricular conditions  in three groups . The results showed that LVAD with LAAO cannulation is appropriate for recovery of the MR heart, and the LVAD with LVAO cannulation is appropriate for treating the AR heart. Worldwide, heart failure (HF) is the major cause of death, according to data from the American Heart Association . HF is cIn valvular regurgitation, valve(s) do not close completely during the ejection and/or diastolic phase. This creates backflow of blood into the atrium and/or the ventricle, decreasing blood flow in the body , 5. The A left ventricular assist device (LVAD) can be used to support heart function as a bridge or as a treatment for patients with HF . The LVAThe purpose of this study is to analyze the effect of an LVAD on AR and MR for different cannulation sites. Using a computational method similar to the numerical method used for developing previously reported cardiac electromechanical models , 13, we 2+ activation. For electrical simulation, we implemented a sinus rhythm by applying the electrical activation time proposed by Durrer et al. [P, V, C, and R denote pressure, volume, capacitance, and resistance, respectively.We used a previously developed canine electromechanical model based on magnetic resonance imaging , 15. Ther et al.  with a br et al.  was usedr et al. , and ther et al. . The schE) per unit volume is the product of cross-bridge detachment rate (gxbT) and the single overlap fraction of thick filaments (SOVFThick):We analyzed several mechanical responses such as 3D adenosine triphosphate (ATP) consumption rate distribution, average ATP consumption rate, pressure waves of the LA, LV, and systemic artery, LV pressure and volume, and LV stroke work. The ATP consumption rate was calculated by integrating the ATP consumption of each node, which represents the myofilament model in one cycle proposed by Rice et al. . In the RMI,Leak and RAO,Leak represent backward flow resistances through the mitral and aortic valves, respectively, in Q, P, and R denote flow rate (mL/min), pressure (mmHg), and resistance (mmHg min/L), respectively, and subscripts MI, AO, LV, LA, and Leak denote mitral valve, aortic valve, left ventricle, left atrium, and regurgitation, respectively.To model AR and MR, we added two additional branches parallel to the compartments of the LA and systemic arteries, which contained flow resistances and one-way valves in the lumped model of the circulatory system. vely, in QMI=PLA−P PLA≤PLV,QAO=PLV−P−1 ATP. The AR heart with the LAAO cannulation site consumed 47% more ATP, and the AR heart with the LVAO cannulation site consumed slightly less ATP, as compared to the AR heart of the control group. The MR heart of the control group consumed 80 s−1 ATP. The MR heart consumed 45% less ATP with LVAD with the LAAO and LVAO cannulation sites, as compared to the control group. The LVAD with LVAO cannulation reduced ATP consumption for all heart conditions.In Figures In We simulated a realistic 3D failing canine heart model under normal , 5% AR, and 5% MR conditions with two cannulation sites for an LVAD, that is, LAAO and LVAO. We analyzed mechanical responses such as ATP contour distribution, average ATP consumption rates, pressures of LV, LA, and aorta, PV loop diagram, and stroke work. The difference between the ATP consumption rates for the control groups was insignificant for the normal, 5% AR, and 5% MR conditions. The LVAD with LAAO and LVAO cannulations reduced the ATP consumption by 45% under the MR condition. Even though LAAO reduced the ATP consumption under the MR condition, it increased the ATP consumption by up to 47% under the AR condition, as compared to that for the control group under the AR condition.In terms of the LV PV loop, isovolumic contraction was observed under the normal condition for the LVAD with LAAO cannulation. LAAO worsened pumping efficacy, in which the heart consumed considerable energy and the EF was zero. Even though the blood circulates with the assistance of the LVAD, the blood trapped in the LV causes thrombosis. In addition, LAAO cannulation under the AR condition is not applicable based on the simulation result because it increased the ATP consumption rate, LV pressure, and stroke work above normal values under the AR condition. In contrast, the LVAD with LVAO cannulation is more appropriate for treating an AR patient because it restores the ATP consumption and maintains the LV PV loop.In the MR heart, the LVAD with LAAO and LVAO cannulation sites succeeded in restoring cardiac functions, which reduced ATP consumption, increased the aortic pressure for coronary perfusion, and provided sufficient cardiac output to the body. Nonetheless, the LVAD with LAAO cannulation is more appropriate for treating the MR heart. This option is suitable for a patient who uses LVAD solely for recovery and not as a bridge to transplantation or as a destination therapy. This is because LAAO cannulation does not alter the diseased LV directly, which is necessary for restoring cardiac functions.The effect of the LVAD with LAAO and LVAO cannulation sites was predicted theoretically under the normal , 5% AR, and 5% MR heart conditions. The results showed that the LVAD with LVAO cannulation restored the hemodynamics of the heart under the AR and MR conditions. For the LVAD with LAAO cannulation, even though this cannulation restored the cardiac hemodynamics under the MR condition, it worsened the cardiac hemodynamics under the AR condition by increasing the ATP consumption, LV pressure/hypertension, and LV stroke work. In conclusion, the LVAD with LAAO cannulation is appropriate for recovery of the MR heart, and the LVAD with LVAO cannulation is appropriate for treating the AR heart.


Reducing time and contrast agent doses are important goals to provide cost-efficient cardiovascular magnetic resonance (CMR) imaging. Limited information is available regarding the feasibility of evaluating left ventricular (LV) function after gadobutrol injection as well as defining the lowest dose for high quality scar imaging. We sought to evaluate both aspects separately and systematically to provide an optimized protocol for contrast-enhanced CMR (CE-CMR) using gadobutrol.This is a prospective, randomized, single-blind cross-over study performed in two different populations. The first population consisted of 30 patients with general indications for a rest CE-CMR who underwent cine-imaging before and immediately after intravenous administration of 0.1 mmol/kg body-weight of gadobutrol. Quantitative assessment of LV volumes and function was performed by the same reader in a randomized and blinded fashion. The second population was composed of 30 patients with indication to late gadolinium enhancement (LGE) imaging, which was performed twice at different gadobutrol doses (0.1 mmol/kg vs. 0.2 mmol/kg) and at different time delays , within a maximal interval of 21 days. LGE images were analysed qualitatively (contrast-to-noise ratio) and quantitatively (LGE%-of-mass).p = 0.538 and p = 0.095, respectively). End-diastolic-volume and end-systolic-volume were measured significantly larger after contrast injection , with a mean difference of 3.7 ml and 2.9 ml, respectively. LGE imaging resulted in optimal contrast-to-noise ratios 10 min post-injection for a gadobutrol dose of 0.1 mmol/kg body-weight and 20 min for a dose of 0.2 mmol/kg body-weight. At these time points LGE quantification did not significantly differ (0.1 mmol/kg: 11% (16.4); 0.2 mmol/kg: 12% (14.5); p = 0.059), showing excellent correlation .Excellent correlation between pre- and post-contrast cine-imaging was found, with no difference of LV stroke volume and ejection fraction  contains supplementary material, which is available to authorized users. Are LV volumes and the subsequently derived LV functional parameters similar before and after contrast injection?Are low doses of macrocyclic contrast agent sufficient to visualize and quantify ischemic and non-ischemic myocardial scar and what is the best time-point for LGE imaging after contrast injection?Contrast-enhanced cardiovascular magnetic resonance (CE-CMR) is a cornerstone of clinical cardiology , 2. DataThe goal of the current study is to address these points systematically and specifically for gadobutrol CE-CMR.All studies were conducted in compliance with the requirements for good clinical practice after approval from the local ethics committee. Each participant provided written informed consent.n = 10), scar detection in chronic coronary disease (n = 4), cardiomyopathy (n = 9) and suspected myocarditis (n = 7).Thirty consecutive patients  who underwent routine CE-CMR for a rest study were included. Indications were viability assessment after myocardial infarction . A standardized balanced steady state free precession (bSSFP) cine-sequence was performed in combination with parallel imaging  and retrospective cardiac gating during expiratory breath-hold . A stack of images covering the whole heart was obtained along the short-axis plane, before and immediately after intravenous administration of 0.1 mmol/kg body-weight of gadobutrol , injected at a rate of 3 ml/s, followed by a 20 ml saline flush, using the same slice position.Cine-bSSFP loops were randomized (crossover design), presented anonymously and displayed for review. Quantitative assessment of all data was performed by the same blinded reader, with 8 years of experience in cardiovascular imaging. Analysis was performed using QMass semi-automated software . Endocardial and epicardial contours were drawn in end-systolic and end-diastolic phases for the assessment of functional parameters, which were normalized to the body-surface-area (BSA) . Stroke volume (SV) and ejection fraction (EF) were calculated using standard formulae.p) was analysed with paired samples t-tests. A value of p < 0.05 was considered significant. The differences in measurements of LV volumes before and after contrast administration were evaluated by means of Bland-Altman plots and correlation was assessed by intraclass correlation coefficient (ICC) statistics. ICC results were interpreted as follows: ICC < 0.40 = poor correlation, ICC 0.41–0.59 = fair correlation, ICC 0.60–0.74 = good correlation, ICC > 0.75 = excellent correlation  who underwent routine CMR for a contrast-enhanced rest study were included. Fifteen patients with known myocardial infarction  and 15 patients with known diagnosis of hypertrophic cardiomyopathy (HCM)  were prospectively enrolled to obtain patients with ischemic and patients with non-ischemic scar. Exclusion criteria were the administration of any contrast agent in the prior 72 h, a history of any severe allergic reaction or hypersensitivity to contrast media, eGFR <60 ml/min and general contraindications to CMR.double-dose) of gadobutrol , injected at a rate of 3 ml/s and followed by a 30 ml saline chaser. Each subject repeated LGE imaging after a minimum of 6 days , by acquiring the same stack of images along the short-axis plane after peripheral bolus injection of 0.1 mmol/kg body-weight (single-dose) of gadobutrol, with same injection rate (3 ml/s) and followed by a saline flush (20 ml at 3 ml/s). To minimize the burden on the patients and to reduce the research scan time of the second examination, images were acquired only twice (i.e. 5 and 10 min after contrast injection).All examinations were performed on a 1.5 T MR scanner scanner . Standardized LGE imaging was performed using 2D turbo-field-echo inversion recovery T1-weighted sequence  with an individually adapted prepulse delay to achieve optimal nulling of the normal myocardium. For each patient, the first LGE imaging study was performed by acquiring a stack of images covering the whole heart along the short-axis plane at 5, 10, 15, and 20 min after peripheral bolus injection of 0.2 mmol/kg body-weight (SI) within the scar as the threshold, and reported as a percentage of total LV mass [MYO), in LGE areas, in LV cavity (LVC) and in air (A) outside the patient’s body, in order to evaluate the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). SNR was calculated for remote myocardium (SNRMYO), LGE areas (SNRLGE) and LV cavity (SNRLVC), by dividing each respective mean SI for standard deviation of air (SDA). CNR values between LGE areas and normal myocardium (CNRLGE-MYO) and between LGE areas and LVC (CNRLGE-LVC) were obtained in order to assess optimal scar delineation within the myocardium and subendocardial area respectively. The following formulas were used:LGE images were randomized (crossover design), presented anonymously and evaluated in consensus by a radiologist and a cardiologist, respectively with 5 and 15 years of experience in cardiovascular imaging. All analyses were done using QMass . LGE quantification was performed by the full width at half maximum (FWHM) method, which uses half of the maximal signal intensity ( LV mass . In addiIQR). Comparison between groups was performed with Wilcoxon signed-rank test for paired data. Comparison across multiple groups was assessed using non-parametric analysis of variance . In particular, Wilcoxon signed-rank test was used to obtain p-values for 0.1 mmol/Kg protocol. Kruskal-Wallis test was used to obtain p-values for 0.2 mmol/Kg protocol, due to the presence of four different time-points; an additional Wilcoxon signed-rank test was performed to assess any significant differences between 15 and 20 min time delays. A value of p < 0.05 was considered statistically significant. The differences in measurements were evaluated by means of Bland-Altman plots and correlation was assessed by intraclass correlation coefficient (ICC) statistics. ICC results were interpreted as follows: ICC < 0.40 = poor correlation, ICC 0.41–0.59 = fair correlation, ICC 0.60–0.74 = good correlation, ICC > 0.75 = excellent correlation [All statistical analyses were performed using dedicated software . Shapiro-Wilk test and histograms were performed to test for normal distribution of the data. Normal distributed data was expressed as mean and standard deviation, non-normal distribution as medians and interquartile ranges . This difference was not significant for the derived parameters SV and EF . There was excellent correlation between pre- and post-contrast LV volumes and EF . Bland-Altman analysis showed a mean difference for post-contrast measurements of 3.7 ml and 2.9 ml, respectively for EDV and ESV  .ol Figs. . At thessingle-dose: 11% (16.4); double-dose: 12% (14.5); p = 0.059), showing excellent correlation .The extent of LGE, expressed in terms of percentage of involvement of myocardial mass, did not significantly differ between the two protocols at their optimal time points (single- and double-dose protocol (p = 0.248), and agreement was excellent . In the non-ischemic group, values were respectively of 7% (6.7) and 10.3% (8.4) . Extent of LGE similarly did not differ between single-dose at 10 min and double-dose at 15 min  is better with the single-dose rather than double-dose, which requires an interval of at least 20 min to wash out the blood pool signal. The combination of these two findings allows a significant shortening of a standardized CE-CMR protocol, which may eventually include native tissue characterization  followed by gadobutrol injection at a dose of 0.1 mmol/kg, assessment of LV structure/function and, 10 min after contrast-injection, LGE imaging  should be transferable considering aspects such as albumin binding, different relaxivities and other potential differences. Our data is also limited to rest examinations. While we expect similar results when the contrast agent is given during adenosine stress, we did not explicitly test for this. Stress-perfusion imaging can be well performed with gadobutrol doses of approximately 0.1 mmol/kg and as such stress-perfusion, cine-imaging and LGE imaging might well fit into a short standardized exam . In caseBased on our data, we provide the scientific evidence to recommend a standardized high-throughput CMR rest protocol giving gadobutrol at a dose of 0.1 mmol/kg before cine-imaging, and performing LGE imaging 10 min after injection. Such a rapid low-contrast dose approach is favourable for patient’s comfort (shorter examination time), patient’s safety (lower dose of GBCA) and economic reasons (lower costs for scan time and contrast media).


Characterization of infarcted myocardial tissue by current cardiovascular magnetic resonance (CMR) methods is predominantly carried out after i.v. application of Gadolinium (Gd)-based contrast agents (CA). However, recent advances in CMR enable the acquisition of parametric maps making use of endogenous tissue properties for diagnostic purposes, which may supersede the need for injection of CA. In the present study, we systematically compared myocardial tissue characterization by Gd-based techniques with intrinsic T1/T2 mapping and their correlation with local cardiac function after experimental myocardial infarction (MI).To this end, we used a murine model of MI and monitored the mice over a period of 21 days (n = 9). MI was induced by chronic ligation of the distal left anterior descending artery (LAD) and comprehensive CMR was performed at 9.4T including cine movies, pre- and post-contrast T1, T2 mapping as well as LGE (Fig. Longitudinal analysis of mice after MI revealed substantial alterations in MR parameters: At day 1 after MI pre-contrast T1 and T2 increased up to 1461 ± 19.2 ms and 37 ± 0.5 ms, respectively, while post-contrast T1 dropped down to 173.9 ± 5.7 ms in infarcted myocardium (Fig. The present study shows that pre-contrast T1 mapping with variable flip angle analysis carried out 1 day after MI predicts the functional outcome after 21 days at least as reliable as LGE. Compared to the latter technique providing plain signal enhancement, the current approach determines quantitative maps with a large dynamic range, which may pave the way for reliable myocardial tissue characterization without any CA.


To demonstrate feasibility of automated 3D volumetry of central pulmonary arteries based on magnetic resonance angiography (MRA), to assess pulmonary artery volumes in patients with pulmonary hypertension compared to healthy controls, and to investigate the potential of the technique for predicting pulmonary hypertension.MRA of pulmonary arteries was acquired at 1.5T in 20 patients with pulmonary arterial hypertension and 21 healthy normotensive controls. 3D model-based image analysis software was used for automated segmentation of main, right and left pulmonary arteries . Volumes indexed to vessel length and mean, minimum and maximum diameters along the entire vessel course were assessed and corrected for body surface area (BSA). For comparison, diameters were also manually measured on axial reconstructions and double oblique multiplanar reformations. Analyses were performed by two cardiovascular radiologists, and by one radiologist again after 6 months.2 BSA) . Mean, minimum and maximum diameters along the entire vessel course were also significantly increased in patients compared to controls . Intra- and interobserver agreement were excellent for both volume and diameter measurements using 3D segmentation . Area under the curve for predicting pulmonary hypertension using volume was 0.998 , compared to 0.967 using manually measured MPA diameter .Mean volumes of MPA, RPA and LPA for patients/controls were 5508 ± 1236/3438 ± 749, 3522 ± 934/1664 ± 468 and 3093 ± 692/1812 ± 474 μl/(cm length x mAutomated MRA-based 3D volumetry of central pulmonary arteries is feasible and demonstrated significantly increased volumes and diameters in patients with pulmonary arterial hypertension compared to healthy controls. Pulmonary artery volume may serve as a superior predictor for pulmonary hypertension compared to manual measurements on axial images but verification in a larger study population is warranted. Pulmonary hypertension (PH) is defined by an elevation of the mean pulmonary artery pressure ≥ 25 mmHg at rest on invasive right heart catheterization . The conAmong other non-invasive methods, measurement of pulmonary artery diameters on axial computed tomography (CT) images has been suggested to assist diagnosis of PH ,8. Altho3D segmentation of pulmonary arteries has been investigated in two previous studies based on CT data. The first study assessed the volume of intrapulmonary arteries, but not of the extrapulmonary arteries . AlthougPurpose of this study was to demonstrate feasibility of 3D segmentation of central pulmonary arteries based on MRA, to assess 3D central pulmonary artery volumes in patients with PH compared to healthy controls, and to investigate the potential of the technique for predicting PH.The study was approved by the institutional review board of the University of Heidelberg and written informed consent was obtained prior to enrolment into the study. 20 consecutive patients  with pulmonary arterial hypertension (WHO classification Group 1) confirmed by right heart catheterization (mean mPAP 53.7 ± 12.6 mmHg) undergoing MRA were prospectively included. Consecutive MRA acquisitions of 21 healthy controls without history of cardiovascular disease and with normal blood pressure  served as reference. Mean body surface area (BSA) calculated according to the Du Bois and Du Bois formula was 1.79 ± 0.20 for patients and 1.84 ± 0.18 for healthy controls (p = n.s.) .A 1.5 T clinical MR scanner  and a standard phased array body coil were used for image acquisition. For contrast-enhanced MRA, a three-dimensional T1-weigthed gradient echo spoiled FLASH sequence supplied by the manufacturer was applied in a coronal orientation . The folAll image analyses were based on the unsubtracted MRA data. For assessment of interobserver agreement, all image analyses were performed by two cardiovascular radiologists. For assessment of intraobserver agreement, one of the two radiologists conducted image analysis for a second time after 6 months without reviewing the previous measurements. Each read was done in a different random order and blinded to the diagnosis.Automated three-dimensional segmentation was performed using three-dimensional model-based image analysis software that was previously validated –16. All For this study, one seed point was placed in the center of the main, right and left pulmonary arteries, respectively . Starting at the seed point, the software automatically performed segmentation of the respective vessel both proximal and distal to the seed point and calculated centerlines along the geometric centroid of each segmented vessel .The reader then visually verified the segmentation result and determined the level of the pulmonary valve, the MPA bifurcation and the take-off point of the upper lobe artery for both RPA and LPA. Pulmonary artery volumes were then computed by the software using the following standardized approach. MPA volume was defined as the volume between a level 5 mm distal to the level of the pulmonary valve and a level 5 mm proximal to the MPA bifurcation. RPA and LPA volumes were defined as the volumes between the start of the RPA/LPA at the MPA bifurcation and the take-off point of the right/left upper lobe artery, respectively. The respective vessel length was computed along the vessel centerline.In addition to that, average vessel diameter perpendicular to the vessel centerline was automatically computed for every 1 mm along the centerline . Mean, mFor comparison purposes, the MPA, RPA and LPA diameters were manually measured on axial reconstructions at standardized locations. MPA diameter was measured at the level of the RPA as done in the Framingham Heart Study  17]. RP. RP17]. Finally, the maximum MPA, RPA and LPA diameters were manually measured by the first reader using double oblique multiplanar reformations (MPR) using the same MRA data sets at the same standardized locations. Again, measurements were performed blinded to the diagnosis and also blinded to all other results and in a randomized order that was different to the randomized orders for 3D segmentation and axial reconstructions.All volumes were indexed to the respective vessel length and corrected for BSA. All diameters were corrected for BSA. Shapiro-Wilk test was performed showing normal distribution of the analyzed data. Data is shown as mean ± standard deviation. The two-sided t-test for independent samples was applied to test for differences between PH patients and healthy controls. Inter- and intraobserver agreements were calculated as Shrout and Fleiss intraclass correlation coefficients. Overall agreement between measurements was assessed using Bland-Altman plots. The limits of agreement were calculated as mean ± 1.96 x standard deviation.AVG) as well as their total volume (VOLTOT) was calculated to predict PH. For comparison, AUC was calculated for MPA diameter, average of RPA and LPA diameters (RPA/LPA diameter) and greatest pulmonary artery diameter measured on axial reconstructions and double oblique MPR.Area under the curve (AUC) using receiver-operating characteristic (ROC) analysis of average volume of RPA and LPA .Automated 3D segmentation was successful and deemed accurate in all cases apart from the MPA in one patient and the RPA in two healthy controls. In these cases, lower contrast in the pulmonary arteries compared to the ascending aorta secondary to suboptimal bolus timing was observed resulting in partial inclusion of the ascending aorta into the segmentation result. The affected segments were excluded from further analysis.Pulmonary artery volumes and diameters based on 3D segmentation were significantly increased in patients with PH compared to healthy subjects Tables  and 2. DAVG corrected for BSA was 0.998  and by VOLTOT corrected for BSA 0.997 . Sensitivity, specificity, positive predictive value and negative predictive value of VOLAVG corrected for BSA were 100%, 95%, 95% and 100% using 2,500 μl/(cm length x m2 BSA) as sex-independent cut-off. For comparison, AUC for predicting PH by diameters manually measured on axial reconstructions was 0.967 for MPA diameter corrected for BSA , 0.990 for RPA/LPA diameter corrected for BSA  and 0.971 for greatest pulmonary artery diameter corrected for BSA . Sensitivity, specificity, positive predictive value and negative predictive value of RPA/LPA diameter corrected for BSA were 100%, 86%, 86% and 100% using 12.5 mm/m2 BSA as sex-independent cut-off. AUC for predicting PH by diameters manually measured on double oblique MPR was 0.953 for MPA diameter corrected for BSA , 0.986 for RPA/LPA diameter corrected for BSA .AUC for predicting PH by VOLMRA-based automated 3D segmentation of central pulmonary arteries is feasible and demonstrated significantly increased volumes and diameters of main, right and left pulmonary arteries in patients with pulmonary arterial hypertension compared to healthy controls. Measurements by 3D segmentation could be reproduced with excellent intra- and interobserver agreement. Furthermore, pulmonary artery volume showed higher sensitivity and specificity for predicting PH compared to pulmonary artery diameters manually measured on axial reconstructions.These findings are well in accordance with previous studies investigating pulmonary artery diameters. Patients with PH have been shown to exhibit significantly increased central pulmonary artery diameters ,19. BesiPrevious studies also demonstrated an only moderate predictive value of MPA diameter manually measured on axial images –10. In oTo our knowledge, this is the first study demonstrating the feasibility of MRA-based 3D segmentation of pulmonary arteries. Similar to CT, acquisition of MRA data can be performed noninvasively and in one breath-hold, but with the additional advantage of not requiring ionizing radiation. This might be particularly useful when performing repeated acquisitions for therapy monitoring. Further studies are needed to assess the value of the presented technique for therapy monitoring as well as predicting treatment response and overall survival, respectively.It might be criticized that the healthy subject group included more males and had a lower mean age compared to the patient group. However, both males and younger subjects tend to have larger pulmonary arteries thus potentially reducing rather than increasing the differences between the PH patient and the healthy subject groups in the present study (4). Another limitation may be the relatively small number of subjects. However, the primary purpose of the present study was to demonstrate the feasibility and the potential of automated MRA-based 3D volumetry justifying a subsequent study in a larger patient population. Besides, inter-exam reproducibility was not investigated because we wanted to avoid repeated contrast medium administration within a short interval.Automated MRA-based 3D volumetry of central pulmonary arteries is feasible and demonstrated significantly increased volumes and diameters in patients with pulmonary arterial hypertension compared to healthy controls. Pulmonary artery volume may serve as a superior predictor for pulmonary hypertension compared to manual measurements on axial images but verification in a larger study population is warranted.S1 Table2 BSA). Data are means ± standard deviation. Measurements are given for the two reads of reader 1 and the read of reader 2. Respective intra- and interobserver agreement are presented in the manuscript.Unit of all values is μl/(cm length x m(DOCX)Click here for additional data file.S2 Table2 BSA. Data are means ± standard deviation. Measurements are given for the two reads of reader 1 and the read of reader 2. Respective intra- and interobserver agreement are presented in the manuscript.Unit of all values is mm/m(DOCX)Click here for additional data file.S3 TableMeasurements are given for the two reads of reader 1 and the read of reader 2. Note that values given here are not corrected for BSA. Respective means as well as intra- and interobserver agreement are presented in the manuscript.(DOCX)Click here for additional data file.


To determine if global strain parameters measured by cardiovascular magnetic resonance (CMR) acutely following ST-segment Elevation Myocardial Infarction (STEMI) predict adverse left ventricular (LV) remodelling independent of infarct size (IS).Sixty-five patients with acute STEMI (mean age 60 ± 11 years) underwent CMR at 1–3 days post-reperfusion (baseline) and at 4 months. Global peak systolic circumferential strain (GCS), measured by tagging and Feature Tracking (FT), and global peak systolic longitudinal strain (GLS), measured by FT, were calculated at baseline, along with IS. On follow up scans, volumetric analysis was performed to determine the development of adverse remodelling – a composite score based on development of either end-diastolic volume index [EDVI] ≥20% or end-systolic volume index [ESVI] ≥15% at follow-up compared to baseline.p < 0.001 for difference). There was good correlation of strain with baseline LVEF (r 0.64–to 0.71) and IS (ρ -0.62 to–0.72). Baseline strain parameters were unable to predict development of adverse LV remodelling. Only baseline IS predicted adverse remodelling – Odds Ratio 1.05 , area under the ROC curve 0.70 .The magnitude of GCS was higher when measured using FT (−21.1 ± 6.3%) than with tagging (−12.1 ± 4.3; Baseline global strain by CMR does not predict the development of adverse LV remodelling following STEMI. Adverse left ventricular (LV) remodelling is associated with poor outcome following ST-segment Elevation Myocardial Infarction (STEMI) –3. ThereMyocardial strain describes the relative change in length of myocardial segments and provides an objective measure of LV function . We haveCMR is the gold standard non-invasive technique for the assessment of LV volumes and IS quantification , 10. MyoIn one study of 74 patients following STEMI , GCS by To date, there have been no reports assessing whether CMR-measured global strain is associated with adverse LV remodelling independent of IS. The primary aim of this study was to determine whether global strain parameters as assessed by CMR-tagging and FT could predict the development of adverse LV remodelling and whether they provide any incremental value to IS.09/H0401/21) and all patients provided written informed consent.In a previously published study assessing the prevalence and extent of microvascular obstruction following STEMI, we recruited patients presenting to a single, regional cardiac centre in the UK with a first STEMI between January 2010 and December 2012 – the inclusion and exclusion criteria have been previously defined . For theCMR was performed on a 1.5 T scanner  using a 6-channel phased-array cardiac receiver coil – see Fig. All images were anonymised and, following completion of the study, were analysed offline by experienced operators blinded to all clinical information. Volumetric analysis and IS quantification were performed at the time of the original study whilst global strain assessment by tagging and FT was performed post-hoc after the original study had been completed.InTag post-processing plugin  for OsiriX  [Strain was evaluated on SAX tagging images (NP) acquired at baseline using the SinMOD algorithm – zerland)  – see Fizerland) . TaggingDiogenes Feature Tracking V6.3  (AS) as previously described [Strain analysis on FT was performed using the escribed , 17, 18.QMass V7.1  (NAR and JNK). All volumes were indexed to Body Surface Area. IS was quantified semi-automatically using the full-width half-maximum technique as previously described [Volumetric, functional and IS assessment were performed using escribed . Adverseescribed t-test, and non-normally distributed data, using Mann–Whitney U-test, and categorical data, using Chi-Squared test. Correlation between parameters was assessed using either Pearson’s correlation coefficient (r) or Spearman’s rank coefficient (ρ) where appropriate.Normality was assessed using the Shapiro-Wilk test, histograms and Q-Q plots. Normally distributed data are expressed as mean ± SD whilst non-normally distributed data are shown as median (interquartile range). Comparison of normally distributed data was performed using paired p < 0.05 were considered statistically significant. Statistical analysis was performed using SPSS version 22.0 Logistic regression was performed to assess predictors of the LV remodelling parameters. Receiver operator characteristic curve analysis was performed for all significant predictors of adverse LV remodelling. All values with n = 39, 60%), thrombolysis , rescue PCI  and late-PCI . Thrombolysis was performed with tissue plasminogen activator analogues where facilities for primary PCI were not available within a two-hour period of symptom-onset. Rescue PCI was performed in patients in whom ST-segment resolution of >50% post-thrombolysis was not achieved. Late PCI describes primary PCI >12 h after symptom onset in the presence of ECG and/or clinical evidence of continuing ischaemia.Table −2 versus 53.5 ml.m−2, mean difference −5.6 ml.m−2, p < 0.001) and an increase in LVEF . Eleven (16.9%) patients had developed adverse LV remodelling – nine (13.8%) patients had an increase in LV end-systolic volume index ≥15%, and six (9.2%) patients had an increase in LV end-diastolic volume index ≥20%.Key patient characteristics are shown in Table n = 65) patients with FT and in 64 patients with tagging . GCS was significantly higher with FT than with tagging . GLS by FT was −13.2 ± 5.5%.Strain analysis was possible in all (ρ = −0.72 for tagging and ρ = −0.61 for FT) and LVEF (r = 0.70 for tagging and r = 0.71 for FT). GLS (FT) also had similar correlation with baseline IS and LVEF . In predicting adverse remodelling, the area-under-the curve with receiver operator characteristic curve analysis for baseline IS was moderate – 0.70   in predicting adverse LV remodelling following STEMI. Our data showed that although global strain parameters appear to have a good correlation with baseline IS, none of them can significantly predict the development of remodelling. The only significant predictor of adverse LV remodelling appears to be baseline IS and this is consistent with previous results .The only other study to evaluate the role of CMR-based global strain at predicting endpoints post-STEMI evaluated FT in isolation (without tagging) and showed that GCS was associated with the development of LVEF > 50% at follow-up . HoweverPrevious studies have shown that strain, as evaluated by both tagging and FT, appears to be decreased in the myocardial segments in the infarcted region compared with non-infarcted segments , 22. ThiOur results suggest that CMR-based global strain may not have a significant role to play in the setting of acute STEMI as has previously been suggested . Larger This study had a relatively small sample size with a small proportion of patients developing remodelling. This may partly represent the beneficial effects of secondary prevention measures  which were prescribed in the majority of patients and known to prevent remodelling post-STEMI . AdditioCMR measured global strain was correlated with baseline IS following STEMI but had no significant value in predicting adverse LV remodelling. Further work is needed to determine if this holds true for the prediction of clinical endpoints post-STEMI.