Circulatory efficiency reflects the ratio between total left ventricular work and the work required for maintaining cardiovascular circulation. The effect of severe aortic valve stenosis (AS) and aortic valve replacement (AVR) on left ventricular/circulatory mechanical power and efficiency is not yet fully understood. We aimed to quantify left ventricular (LV) efficiency in patients with severe AS before and after surgical AVR.Circulatory efficiency was computed from cardiovascular magnetic resonance (CMR) imaging derived volumetric data, echocardiographic and clinical data in patients with severe AS (n = 41) before and 4 months after AVR and in age and sex-matched healthy subjects (n = 10).In patients with AS circulatory efficiency was significantly decreased compared to healthy subjects . There were significant negative correlations between circulatory efficiency and LV myocardial mass , myocardial fibrosis volume , end systolic volume  and NT-proBNP  and significant positive correlation between circulatory efficiency and LV ejection fraction . After AVR, circulatory efficiency increased significantly in the total cohort . However, in 10/41 (24%) patients, circulatory efficiency remained below 10% after AVR and, thus, did not restore to normal values. These patients also showed less reduction in myocardial fibrosis volume compared to patients with restored circulatory efficiency after AVR.In our cohort, circulatory efficiency is reduced in patients with severe AS. In 76% of cases, AVR leads to normalization of circulatory efficiency. However, in 24% of patients, circulatory efficiency remained below normal values even after successful AVR. In these patients also less regression of myocardial fibrosis volume was seen.Trial Registration clinicaltrials.gov NCT03172338, June 1, 2017, retrospectively registered. Aortic valve stenosis (AS) is a frequent heart valve disease worldwide that exposes the left ventricle (LV) to chronic pressure overload –3. This Circulatory efficiency reflects the ratio between total LV work and the work required for maintaining cardiovascular circulation –9. The aIncreases in LV pressure and myocardial hypertrophy can contribute to a reduction of cardiac efficiency, whereas small ventricles with normal LV ejection fraction (LVEF) show higher cardiac efficiency. Accordingly, the concept of cardiac efficiency has been analyzed in some initial studies of arterial hypertension, heart failure and valve disease , 11–14. A reduced surrogate marker of circulatory efficiency in patients with different stages of AS has been found using a recent noninvasive and radiation-free CMR method . In the A total of 41 patients with severe AS (according to current diagnostic guidelines ) were inAll patients underwent cuff-based blood pressure measurements, blood collection, clinical, echocardiographic and CMR examination before and 4 (± 38 days) months after surgical AVR. The mean and maximum pressure gradient across the aortic valve was measured using Doppler echocardiography (5-chamber-view). Mitral regurgitation was quantified using standard echocardiography. 10 age- and sex-matched controls  using a five-element cardiac phased-array coil. Gapless balanced Turbo Field Echo (bTFE) cine 2-dimensional short axis sequences were obtained using a previously applied CMR protocol  for LV vABC, isovolumetric contraction time tIVC and the aortic pressure gradient. 4D data were analyzed using GT Flow program . Total systolic contraction time tCS is the sum of tABC and tIVC. The temporal solution was 25 timesteps for 4D flow measurements and 30 timesteps for 2D flow measurements. We could show that 4D flow measurements with 25 timesteps are a feasible alternative to flow measurements with higher temporal solution in a prior study [4-dimensional and 2-dimensional velocity encoded (VENC) CMR was obtained using a previously described CMR protocol . 4-D VENor study .CMR-FT based strain analyses were performed using commercially available software provided by Medis . FT was performed in the end-diastole and end-systole cardiac phases, at the endo- and epicardial borders. Global longitudinal strain (GLS) was assessed by averaging the peak systolic strain values of 17 segments extracted from three long axis  images , while global circumferencial strain (GCS) was acquired from three short axis images  using a 16-segment model.Power is the rate of transferring or converting energy per unit time. The ratio of the power needed to pump a given blood volume against a given afterload  to the power used by the heart to perform one heartbeat  is described as circulatory efficiency (CircE). LVMP was defined as the surrogate power of the LV to perform one heartbeat since the applied method is an estimation , 19:\docwall = myocardial wall volume, σwall = wall stress, tCS = LV systolic contraction time.VWall stress was calculated using a simplified approach of the law of Laplace:SYS = LV peak systolic pressure, RBP = mean radius of the blood pool, Swall = mean myocardial wall thickness. Swall and RBP during systole were averaged from LV segmentations considering the LV as a cylindrical geometry for correction of potential regional differences. Psys = sum of the systolic blood pressure measured at the right arm and the maximum pressure gradient across the aortic valve. LVMP was indexed to body surface area (BSA).PCirculatory power (CP) is defined as the hydrodynamic power distally to the valve representing the power needed to maintain effective blood flow against systemic vascular resistance (afterload).eff = effective cardiac output. The dimension of COeff is L/min. COeff is the product of heart rate and SVeff. SVeff = (EDV-ESV) * (1-regurgitation fraction).MAP = mean arterial pressure, COCirculatory efficiency (CircE) is the ratio between CP and LVMP.Calculation of extracellular volume (ECV) was done using a prior described method , 21:\docmyo = LV midwall myocardial T1 value, blood = LV blood pool T1 value, and pre and post refers to the measurement before and after contrast administration. Absolute ECV was calculated using the following equation: aECV = LV myocardial volume*ECV. LV myocardial volume = LV mass/1.05, where 1.05 is the myocardial density given in g/ml.As stated in a prior study , parametData are presented as mean ± SD unless stated otherwise. Shapiro–Wilk test was used for normality testing. A paired two-tailed Student’s t-test or Wilcoxon test was performed where appropriate to investigate differences between pre- and post-operative measurements. Unpaired two-tailed Student´s t-test or Mann–Whitney-U Test was performed to investigate differences between disease groups and controls as appropriate. Pearson´s chi-square test was performed to investigate differences in unpaired categorical variables. McNemar test was used to test for differences in paired categorical data before and after an intervention. A linear regression model was used to identify the relationship between variables. The significance level was set at 0.05. Data were analyzed using SPSS  and Stata .Table In patients with severe AS, CircE was lower  compared to healthy controls Fig. .Fig. 3Le2, p < 0.001)  and showed no difference to healthy controls  , ESV  and LVEF .2, p < 0.001) and showed no differences to healthy controls  . Improvement of CircE significantly correlated to decrease of LVMP . Decrease of LVMP significantly correlated to changes of aortic pressure gradient , LVM , ESV , EDV  and LVEF . Furthermore, improvement of CircE did not correlate with prosthesis size (p = 0.409).The lowest value for CircE in controls was 10%. 10/41 (24%) patients displayed CircE of < 10% after AVR. Between the two groups without (n = 10) and with restored CircE (n = 31) after AVR, we found the following effects:Pre-operative findings: In patients without restored CircE 70% were male, LVEF was lower  and diastolic RR was higher . There was no difference in CircE, mean gradient across the aortic valve, NYHA status or markers for hypertrophy or fibrosis Tables . No paraPost-operative findings: Reduction in fibrosis (aECV) , improvement in CircE  and in NYHA  was only significant in patients with restored CircE. Improvement in LVEF  was only significant in patients without restored CircE after AVR. Mean gradient across the aortic valve  and LVMP  were higher in patients without restored CircE, however, there was no significant difference in post-operative LVP, NT-pro-BNP, cardiac function, NYHA status or markers for hypertrophy between patients with and without restored CircE. Furthermore, there were no differences in pre- to post-AVR changes of LV mass, aortic valve gradient and NT-proBNP between patients with and without restored CircE  Fig. .Fig. 6CoWe quantified a surrogate marker of circulatory efficiency (CircE) longitudinally in patients with severe AS before and after surgical AVR using a non-invasive CMR technique. We found CircE to be reduced in patients with AS and lower CircE was associated with pronounced LV hypertrophy and fibrosis and reduced LV function. After surgical AVR, CircE did not increase and normalize in an important fraction of patients (24%). These patients also showed less reduction in LV myocardial fibrosis volume compared to patients with restored CircE after AVR. Improvement of CircE was significantly influenced by the decrease of LVMP. Furthermore, decrease of LVMP was significantly affected by changes of aortic pressure gradient, LVM, ESV, EDV and LVEF. Therefore, decrease of LVMP and improvement of CircE is affected by the decrease of afterload but is also influenced by cardiac reverse remodeling.Myocardial adaptation processes like hypertrophy and fibrosis in patients with AS lead to higher LV energy demand and reduced efficiency –3, 9. IfIn hypertrophied and failing hearts, a switch from aerobic mitochondrial fatty acid oxidation to anaerobic glycolysis has been described, which decreases myocardial efficiency due to inefficient ATP generation and increased adenosine triphosphate (ATP) consumption for other non-contractile purposes . Even inMyocardial efficiency is defined as the ratio between external work and myocardial energy consumption , 29. TheIn our study, we calculated circulatory efficiency by measuring mechanically generated power of the LV necessary to perform contraction against a given afterload following the law of Laplace and considering only geometrical parameters assessed by CMR. We recently demonstrated a reduced circulatory efficiency in patients with AS and different grades of severity . The preHansson and colleagues previously quantified efficiency in mainly asymptomatic AS patients with and without heart failure and demonstrated reduced efficiency in patients with impaired LVEF compared to controls . Our finAVR has beneficial effects on prognosis mainly due to reverse remodeling , 31. In In our study, CircE did not normalize in 10 (24%) patients. Mean value for preoperative LVEF was lower and diastolic blood pressure was higher in the non restored group. However, looking at the individual 10 patients with non restored CircE after AVR, 4 patients displayed LVEF lower than 45%, but in 6 patients LVEF was higher than 56%, showing the heterogeneity of the non restored group. NT-proBNP did not reach statistical significance between restored and non restored group. However, in general, patients who did not restore after AVR seem to be the patient group with patients, who were slightly sicker, although not many significant differences could be found. Postoperatively, NYHA and aECV only improved in the restored group and LVEF only improved in the non-restored group. Mean aortic pressure gradient was higher in the non restored group, however, postoperative mean aortic pressure gradient of 15 mmHg does not seem to be clinically relevant. Furthermore, the combined parameter LV pressure, which is part of the formula of CircE, was not significantly different between groups.Statistically, we did not find any preoperative parameter that was predictive for patients showing postoperative non restored CircE and we could also not describe a main component, which was causative for showing non restored CircE after AVR. Further studies are needed and the two groups, especially the non restored group, is too small, however, circulatory efficiency taking into account different risk factors  might be useful to categorize patients with pressure overload, who have not yet surpassed cut off values of single parameters.Only patients with restored CircE after AVR showed improvement of CircE and myocardial fibrosis after AVR. Similar results were demonstrated by Güclu and colleagues where 4 out of 10 AS patients without efficiency improvement after AVR did not improve in exercise capacity after AVR . Hence, We found high CircE to be associated with high GLS, which is a measure of subclinical LV dysfunction and a predictor of reverse remodeling and outcome after AVR –36. GLS Pressure overload can trigger cellular pathways that lead to myocardial adaptation processes such as hypertrophy and fibrosis and is associated with heart failure in the long term –3. InterIn our cohort of patients with severe AS we describe a reduction of LV mass and absolute fibrosis volume after AVR, however, fibrosis fraction (ECV) increased short term after AVR. This is in line with longitudinal biopsy studies from 1989 and recent CMR studies from Treibel TA et al., who described different cohorts of patients with severe AS and AVR and postoperative faster regression of myocardial mass than regression of fibrosis, which leads to an initial increase of fibrosis fraction short term after AVR, but constant decrease of the absolute amount of fibrosis load , 39.In regard to efficiency we found a correlation of low pre-operative CircE with high post-operative fibrosis load. Moreover, there is only a significant reduction in absolute fibrosis volume in patients with restored CircE after AVR and not in patients with non-restored CircE after AVR. This suggests that reduced CircE in patients with severe AS is accompanied with delay in reverse remodeling after AVR at least concerning diffuse fibrosis since regression of myocardial mass and normalization of EDV and ESV is seen in all patients. In line with this suggestion recent literature studied the impact of myocardial fibrosis in patients with AS on LV reverse remodeling after aortic valve therapy. It was described that higher amount of myocardial fibrosis pre-treatment was associated with delay in normalization of LV geometry and function but not per se with absence of reverse remodelling and clinical improvement after treatment .There was a high prevalence of bicuspid aortic valve (BAV) patients in our cohort. Prior studies comparing severe AS in patients with BAV and trileaflet aortic valve have shown that patients with trileaflet AS have a greater prevalence of cardiovascular risk factors and worse survival after AVR . HoweverIn the present study, we did not find differences in LV power and circulatory efficiency, nor in markers for hypertrophy or fibrosis between AS patients with BAV and trileaflet AS before and after AVR. Looking at the patient characteristic there were no differences in age, aortic pressure gradient and cardiovascular risk factors such as diabetes, arterial hypertension and dyslipidemia. BAV patients showed a lower systolic blood pressure  and lower pre-operative pulse pressure , however, this did not have a relevant impact on the other parameters. It might be, that BAV and trileaflet AS patients in our patient cohort, were more comparable in their patient characteristics than in other studies describing relevant differences between these patients.In a former publication we have described abnormal flow profiles in the ascending aorta to be present before and after AVR in the majority of patients . In otheComputing of myocardial energetics focused on systole, since it accounts for the majority of the heart’s energy expenditure, without further consideration of the diastole, although diastolic relaxation is an active ATP-consuming process. However, little is known about myocardial energetics in diastole, and more research is needed to unveil the underlying mechanisms.The parameter circulatory efficiency does not represent a true measurement but a mathematical formula that integrates the numerical information of a total of eight variables . Because the parameter circulatory efficiency cannot be measured, neither as a single nor as a repeat measurement, intra- and/or inter-observer variabilities and scan-rescan variability cannot be computed. However, parameters of cardiac power and efficiency have been calculated using clinical established CMR LV volumetric and flow measurements. Good reproducibility of CMR LV volumetric, 2D and 4D flow measurements have been shown in several studies , 44, 45.Moreover, this study was a purely mechanical approach without metabolic measurements of myocardial oxygen consumption derived by PET or invasive hemodynamic measurements that assumed LVMP to be the surrogate potential power generated by LV contraction following the simplified law of Laplace. Furthermore, the pressure recovery phenomenon was not considered since aortic pressure gradients were assessed using Doppler echocardiography as currently recommended by guidelines . Future In summary, the quantification of a surrogate marker of CircE in patients with severe AS before and after AVR has been demonstrated using a non-invasive CMR-based approach.CircE was reduced in patients with AS and lower CircE was associated with pronounced hypertrophy and fibrosis and reduced LV function. After AVR, CircE increased and normalized in the majority of patients. In 24% of patients, CircE did not normalize and these patients showed no improvement of myocardial fibrosis compared to patients with restored CircE after AVR.CircE, reflecting a combined parameter of LV adaptation to increased workload, could be valuable in the search for finding optimal timing of intervention in patients with AS to improve optimal long-term outcomes.


Most of the current studies on myocardial strain are mainly applied in patients with sinus rhythm because the image quality of arrhythmias obtained with conventional scanning sequences does not meet diagnostic needs. Here, we intend to assess left ventricular (LV) global myocardial strain in patients with arrhythmias with 3 Tesla magnetic resonance (MR) and a new cine sequence. Thirty-three patients with arrhythmia and forty-eight subjects with sinus rhythm were enrolled in the study. LV myocardial thickness, cardiac function, myocardial strain and the apparent contrast-to-noise ratio (CNR) were all measured and compared using images generated by the real-time temporal parallel acquisition technique (TPAT) and the conventional cine sequence. In the arrhythmia group, the image quality of real-time TPAT was significantly better than that of the conventional cine sequence. In the arrhythmia group, the LV global peak radial strain and global peak circumferential strain values of real-time TPAT were significantly different from those of the conventional technique . There was no significant difference in global peak longitudinal strain between real-time TPAT and the conventional technique . There was no significant difference in the cardiac function parameters between the two techniques (p > 0.05), but there was a significant difference in 12 segments of the LV wall thickness between the two sequences (p < 0.05). In the sinus rhythm group, image quality using real-time TPAT was comparable to that using the conventional technique, and there was no significant difference in any of the indices (p > 0.05). Real-time TPAT is an effective method for detection of left ventricular myocardial deformation in patients with arrhythmia. In particular, left ventricular (LV) global myocardial strain is superior to left ventricular ejection fraction (LVEF) for predicting cardiac adverse events2. LVEF is in the normal range in most arrhythmia patients without structural heart disease, but myocardial contractility is abnormal, which may lead to ventricular systolic dysfunction3 and may increase the risk of sudden death4. Therefore, it is important to evaluate myocardial deformation in patients with arrhythmia, and an evaluation index of ventricular wall contractility is needed.Over recent years, cardiac magnetic resonance (CMR) myocardial strain has developed rapidly and has been used for assessing myocardial deformation in many cardiovascular diseases, such as coronary artery disease and cardiomyopathy5. Therefore, the TPAT can achieve faster and more stable image reconstruction than real-time CMR imaging. However, it has not been used to assess LV myocardial strain in patients with arrhythmia.CMR tissue tracking (CMR-TT) technology is widely used in patients with sinus rhythm, but it remains unclear whether it can be used in patients with arrhythmia. The large variation in heart rate can lead to motion artefacts in images acquired by conventional cine sequences with retrospective electrocardiogram (ECG)-triggering techniques . With the rapid development of fast MR imaging techniques, real-time cardiac cine sequences have been gradually developed and applied in the clinic. In this case, the temporal parallel acquisition technique (TPAT) is used as a parallel imaging technique, which is based on the use of multi-channel coils for data acquisition and view-sharing schemes for image reconstruction. Compared with other real-time CMR methods based on the compressed sensing (CS) theory, the TPAT does not require nonlinear iterative methods or manual adjustment of penalty parameters for image reconstructionIn this prospective study, we sought to investigate the feasibility of the TPAT for evaluating LV myocardial strain in patients with sinus rhythm and then to assess LV myocardial strain in patients with arrhythmia.In the arrhythmia group, 17 patients had atrial arrhythmias, and 16 patients had ventricular arrhythmias. Heart rate fluctuations were 3 to 90 beats/min (average 31.55 ± 22.72 beats/min), and heart rate variability was 10.55 ± 7.73% . There was no significant difference in global peak longitudinal strain between the real-time TPAT and the conventional technique . There was no significant difference in the LV global peak radial strain, global peak circumferential strain or global peak longitudinal strain in the sinus rhythm group ; however, in the sinus rhythm group, there was no significant difference in image quality between the two methods  Table .Table 3TIn the sinus rhythm group, there was no significant difference in the 16 segments of LV myocardial thickness between the real-time TPAT and the conventional technique p > 0.05). However, in the arrhythmia group, except for 4 segments [the inferoseptal and inferolateral segments of the LV basal level and the anterior and lateral segments of the LV apical level], there were significant differences in the remaining 12 segments (p < 0.05) (Table . HoweverThere was no significant difference in the cardiac function indices between the two groups (p > 0.05) Table .6. CMR-TT imaging can be used to analyse myocardial motion and torsion8. The advantage of this approach is that it can quantitatively detect subtle myocardial deformation in coronary artery disease, cardiomyopathy, heart failure and other cardiac diseases11. Moreover, it can be measured on a cine sequence without special sequence scanning, and many studies have shown that CMR-TT technology has good repeatability, accuracy, and stability13. Strain is a basic parameter of CMR-TT. It changes continuously throughout the cardiac cycle, and myocardial deformation occurs in three directions14. Negative strain values represent myocardial circumferential and longitudinal shortening, while positive strain values represent radial thickening15. CMR studies have sparsely reported strain performance in patients with arrhythmia. In this study, the conventional technique and the real-time TPAT were used to explore LV myocardial strain and its characteristics in patients with arrhythmia.Myocardial strain is closely related to the anatomical structure of heart muscle fibreset al. used displacement encoding with stimulated echoes (DENSE) strain to assess myocardial deformation in 100 patients after cardiac resynchronization therapy. DENSE is a rapid imaging technology. Myocardial strain was analysed using cine images obtained from DENSE technology, and the results showed that the combined use of strain imaging and clinical risk models represented a promising paradigm to predict patients' risk of arrhythmia16. In the present study, we applied the real-time TPAT, which is also a rapid imaging technique, and found that patients with arrhythmia had impaired strain indices. Heermann et al. analysed the LV strain characteristics of 16 patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) using CMR feature tracking technology. The absolute values of LV global longitudinal strain and radial strain of ARVC were lower than the normal reference values18. Moreover, Orwat et al. enrolled 372 patients after repair of tetralogy of Fallot and analysed the longitudinal strain, circumferential strain and radial strain using the CMR feature tracking method. The results showed that global longitudinal strain, circumferential strain and radial strain were all impaired and were associated with the New York Heart Association (NYHA) class and symptomatic deterioration19. In our study, the arrhythmia group included 17 patients with atrial arrhythmias and 16 patients with ventricular arrhythmias, and the global peak longitudinal strain, circumferential strain and radial strain in these patients were also lower than the normal reference values.This study showed that there was no significant difference in left ventricular global peak longitudinal, circumferential or radial strain as well as cardiac functional indices and myocardial thickness parameters between the real-time TPAT and the conventional technique in the sinus rhythm group, which indicated that the real-time TPAT had good performance feasibility. After testing the feasibility in the sinus group, we tried this sequence in arrhythmia patients. In the arrhythmia group, the image quality was improved with the TPAT compared to with the conventional sequence. Furthermore, there were significant differences in assessing the LV global peak radial strain and global peak circumferential strain values between the TPAT and the conventional technique, but there was no significant difference in the global peak longitudinal strain. Bilchick In the arrhythmia group, there were significant differences in 12 LV myocardial segments of the wall thickness between the two techniques. This result indicates that LV wall motion artefacts in patients with arrhythmia can affect the evaluation of heart structure with the conventional technique. In the arrhythmia group, there was no significant difference in the cardiac function parameters between the two technologies, which may be due to the real-time TPAT technology being as suitable as the conventional technique for capturing EDV and ESV in the cardiac cycle. To a certain extent, the real-time TPAT can be applied for the measurement of LV peak strain. However, in the condition of patients with fast ventricular rate, the temporal resolution of real-time TPAT maybe not enough for capturing EDV and ESV accurately. Further study is needed to clarify the suitable range of ventricular rate for real-time TPAT technique.21. Bassett et al. evaluated the performance of eight-fold-accelerated cine MRI sequences using compressed sensing in animals with tachycardia at 3 T, revealing that eight-fold real-time cine MRI sequences with k–t SPARSE-SENSE can achieve acceptable diagnostic quality and relatively accurate LV functional measurements of tachycardia22. However, image reconstruction of compressed sensing requires nonlinear iterative reconstruction and manual adjustment of the penalty parameter to balance data consistency and sparse constraints.In recent years, compressed sensing for real-time cardiac cine sequences has also been developedThe current study has some limitations. First, the sample size was relatively small. Second, the cardiac morphology and functional parameters of patients with different arrhythmias were not further analysed. Third, compared with that of the conventional sequence, the spatial and temporal resolution of the real-time TPAT sequence was inferior, but for patients with arrhythmias, it could significantly improve image quality.For sinus rhythm patients, we compared the real-time TPAT with conventional cine sequences, and the results showed that the TPAT could obtain similar image quality to conventional cine sequences. Therefore, the real-time TPAT can be used as an alternative sequence in patients with sinus rhythm. For patients with arrhythmia, the real-time TPAT can improve the image quality, and it is a scan sequence suitable for these patients to detect left ventricular myocardial deformation.The study was approved by the ethics committee of Beijing Anzhen Hospital, Capital Medical University, and the number was 2016031×. The study was carried out under relevant guidelines and regulations (Declaration of Helsinki). All participants gave written informed consent.The study included 81 patients  who underwent CMR examination. Their indications for CMR included arrhythmia, myocardial infarction, hypertension, myocardial disease, heart failure, and myocarditis. According to the cardiac rhythm status during the examination, the patients were classified into the arrhythmia group (n = 33) or the sinus rhythm group (n = 48). In the arrhythmia group, ventricular premature beats, atrial fibrillation, and bigeminal beats were found, while in the sinus rhythm group, the cardiac rhythm was stable, and the R-R interval was equal.All CMR scans were performed on a 3 T MR system  with a 32-channel cardiac coil. The patients were trained to hold their breath before scanning. During scanning, patients were scanned by conventional cardiac cine sequences with retrospective ECG-triggering  and real-time cardiac cine sequences with the TPAT . Both sequences were based on balanced steady-state free precession (bSSFP) readouts to obtain a better image signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) between the myocardium and blood pool. Short-axis, four-chamber, three-chamber and two-chamber views of LV were acquired. The parameters of the TPAT were optimized to realize real-time cardiac imaging. The optimization included (1) using a lower spatial resolution (2.9 mm × 2.1 mm) and making the bandwidth (1359 Hz/pixel) as high as possible to shorten the echo spacing and thus improve the temporal resolution and to reduce banding artefacts; (2) setting the acquisition window equal to cardiac phases × temporal resolution to realize real-time cardiac imaging; and (3) optimizing the acceleration factor of the TPAT by balancing the temporal resolution and signal-to-noise ratio. The scanning parameters of the conventional technique and the real-time TPAT are shown in Table All cine images were transferred to an off-line workstation  for analysis.Global LV peak strain analyses were performed using post-processing software . At end-diastole, endocardial and epicardial boundaries were manually delineated in 2-, 3-, 4-chamber and short-axis views, and papillary muscles were included within the endocardial borders. In the short-axis orientation, the insertion points of the right ventricle were manually delineated. Then, in 2-, 3-, and 4-chamber view images, straight lines were made at the mitral annular level and from the midpoint of the mitral annulus to the apex. After the automated tracking algorithm was applied, automatically rendered contours were reviewed and corrected. The analysis was performed over the entire cardiac cycle, resulting in a strain-time curve  segmental model for 16 segments  in short-axis orientationGlobal left ventricular function analysis was performed using Siemens Syngo Argus post-processing software. LV endocardial and epicardial borders were manually traced in both the end-diastolic and end-systolic phases in the short-axis view. To reduce observer variability, LV papillary muscles were included as part of the LV end-diastolic volume and end-systolic volume and were excluded from the LV mass. Parameters of LV function were calculated by an automated algorithm, including LVEF, LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), stroke volume (SV), cardiac output (CO) and myocardial mass (MM). To obtain standardized parameters, the above parameters except LVEF were adjusted according to body surface area.The overall image quality of each cine sequence was assessed using a four-point scale . All the analyses were performed by two independent radiologists on an off-line workstation, and if the two ratings were inconsistent, then a consensus was reached through discussion.blood, S Myocardial, SD blood, and SD Myocardial, respectively. The CNR between the blood pool and myocardium was also calculated according to a previous work24 and was formulated as the following equation (1):CNR was measured by one radiologist. The sizes of the region of interest (ROI) in the blood pool and myocardial structure were contoured on the images obtained by the conventional technique according to the size of the heart at the LV basal, middle and apical levels. Next, the ROIs were copied to images acquired by the real-time TPAT. Since the spatial resolution was different between the two techniques, it was necessary to manually adjust the copied ROIs to ensure that the contoured ROIs on the images of the two techniques were similar. The signal intensity and standard deviation of the blood pool and myocardium were measured and expressed as S All statistical analyses were performed using the Statistical Package for the Social Sciences . Continuous variables are presented as the mean ± standard deviation. Differences between means were tested with the paired t-test and one-way analysis of variance as appropriate. Categorical variables were analysed using the Pearson Chi-square test. Comparisons of parametric variables between the conventional technique and the real-time TPAT were performed using paired t-tests. The Wilcoxon rank-sum test was used to compare the image quality score. The agreement was tested by calculating the mean bias from Bland-Altman analysis. Categorical variables are expressed as frequencies or percentages. A p-value of less than 0.05 was considered statistically significant, and all statistical tests were 2-sided.


The author’s contribution up to 1990 was reviewed in part I and the echo contributions from 1991 to 2020 will be reviewed in part II. These include defining the relationship between the quantity of shunt across the atrial septal defect (ASD) and the diameter of ASD by echo and angio on the one side and the stretched diameter of the ASD on the other; echocardiographic assessment of balloon-stretched diameter of secundum ASDs; development of echocardiographic predictors of accomplishment of percutaneous closure of ASDs with the buttoned device, highlighting limitations of echocardiography in comprehensive assessment of mixed type of total anomalous pulmonary venous connection; description of follow-up echocardiographic results of transcatheter closure of ASD with buttoned device; review of ultrasound studies; depiction of collaborative echocardiographic and Doppler studies; echocardiographic appraisal of the outcome of balloon pulmonary valvuloplasty; editorials; ventricular septal aneurysm causing pulmonary outflow tract obstruction in the morphologic left ventricle in corrected transposition of the great arteries; dependability of echocardiographic assessment of angiographic minimal diameter of the ductus; occurrence of supravalvular pulmonary artery stenosis after a Nuss procedure; echocardiographic assessment of neonates who were suspected of having heart disease; role of echocardiographic studies in the appraisal of patent ductus arteriosus in the premature babies; and the role of pressure recovery in explaining differences between simultaneously measured Doppler and cardiac catheterization pressure gradients across outflow tract stenotic lesions. In the first paper , the autAs of early 1990s, device selection for transcatheter closure of the ASDs was mostly on the basis of measured balloon-stretched diameter of the ASD immediately preceding device closure. However, balloon sizing is relatively cumbersome, requiring use of large balloon catheters. Therefore, we examined other methods of evaluation of size of the ASD, such as transthoracic echocardiography, pulmonary-to-systemic flow ratio (Qp:Qs), and angiography to see if the balloon-stretched diameter of the ASD can be predicted . The datp > 0.1) to the angiographic diameter but was smaller (p < 0.01) when compared to the stretched diameter of the ASD. When the relationship of these parameters was look at, the Qp:Qs ratio and ASD diameter by angiography have a noteworthy (p < 0.05) correlation with the stretched diameter but with relatively low correlation coefficients: r = 0.55 and 0.54, respectively  diameter of the ASD was 9.9 ± 4.1 mm with a range of 4 to 17 mm, and the angiographic size of the ASD was 7.9 ± 2.5 mm (range of 3.8 to 12 mm). The balloon-stretched diameter in these patients was 16.1 ± 5.3 mm with a range of 5 to 23 mm. The two-dimensional (2D) echocardiographic size of the ASD was similar . The stretched ASD diameter may be calculated by the following formula: (1.05 × echo size in millimeters) + 5.49 mm. In this study [As stated in the preceding paper, stretched size of the ASD, measured by balloon sizing during cardiac catheterization, was commonly used in the early 1990s in the selection of the sizes of the devices for percutaneous occlusion of the secundum ASDs. In the preceding study , we evalis study , we prosp > 0.1) from the measured stretched ASD size. The correlation between predicted and measured stretched ASD diameters was good   . The varTo improve the accuracy, we suggested that an average of measurements from two subcostal (short and long axis) views be utilized to calculate the ASD size. On the basis of these data, it was concluded that stretched ASD size may be predicted with reasonable accuracy by transthoracic 2D echocardiographic ASD dimensions obtained prior to cardiac catheterization, which in turn may be utilized to select the diameter of device for occlusion of the ASD .While these studies ,3 were cEchocardiographic finding of tricuspid atresia with persistent truncus arteriosus  were revPercutaneous closure of ostium secundum ASDs with the buttoned device was demonstrated to be safe and effective, as shown in multiple studies published as of the mid-1990s. The decision to insert the device as well as the size of the device selected was mostly on the basis of the balloon-stretched size of the atrial defect, measured during catheterization studies, as alluded to in the two preceding studies ,3. HowevTwenty-nine patients with secundum ASD were assessed for percutaneous closure during a 46-month period ending in August 1992. Successful device implantation was accomplished in 15 patients, and these formed group A while the left over 14 children in whom the device closure could not be performed were assigned to group B. Echocardiograms performed prior to the procedure were analyzed by the authors who were not aware of the results of transcatheter closure attempt. Echocardiographic data acquired were the diameter of the ASD, length of atrial septum (LAS), dimension of the superior and inferior rims in apical and subcostal views , largestp > 0.1) between both groups. The size of the ASD  was smaller (p < 0.05 to < 0.01), the ratio of ASD to LAS was lower (p < 0.05), the superior rims as measured in the subcostal long-axis view was shorter (p < 0.05), and ratios of superior and inferior septal rims to ASD was larger (p < 0.05) in group A than in group B. Multivariate logistic regression analysis and contingency tables showed that diameter of ASD ≤ 15 mm, ASD/LAS ratio ≤ 0.35, and ratio of superior rim to ASD ≥ 0.75 are predictors of good outcome. The greater the number of predictive factors, the higher the probability for successful device occlusion of ASD  is an uncommon congenital heart defect (CHD) constituting approximately 1% of all CHDs. On the basis of site of drainage of the pulmonary veins, the TAPVC patients are classified into supra-cardiac, cardiac, infra-cardiac, and mixed types. The mixed type of TAPVC comprises 5% to 10% of all TAPVCs. We presented echocardiographic and angiographic findings of two cases of mixed TAPVC, with the intent of highlighting the limitations of echocardiography in comprehensive assessment of this rare anomaly . FollowiTransthoracic echocardiogram in case 1 showed dilated right atrium (RA) and right ventricle (RV) with a common pulmonary venous confluence a and a vOn the basis of the experience in these two cases, we recommended angiographic definition of all pulmonary veins in mixed type of TAPVC at that time . With ton = 14), group II with presumed paradoxical embolism (n = 5), and group III with right-to-left shunt (n = 1). Clinical, chest roentgenogram, and echocardiographic evaluation was undertaken at two weeks, at three, six, and twelve months following device occlusion, and subsequently every year. Data at follow-up in these 20 patients were available for review at 29 ± 11 months (range 16 to 52 months) after device implantation. The majority of patients received aspirin (5 to 10 mg/kg/day) orally for 12 weeks following the device placement.Immediate and short-term results demonstrated that transcatheter closure of the ASD with the buttoned device is feasible, safe, and effective. No long-term results were documented as of early 1990s. Therefore, we evaluated long-term results of buttoned device implantation in 20 of 22 consecutive patients (91%) through August 1992 [p < 0.01) following ASD closure. The RV dimension decreased from 2.3 ± 0.6 to 1.7 ± 0.3 cm after occlusion (p < 0.01) and stay diminished (1.6 ± 0.46 cm) at latest follow-up evaluation (In group I (14 subjects with left-to-right shunt), the Qp:Qs fell from 2.1 ± 0.5 to 1.08 ± 0.2  the day after ASD occlusion, and trivial shunts persisted in three of fourteen (21%) patients at follow-up. Two of these children had cardiac catheterization one year following device implantation, and no left-to-right shunt was found by oximetry and no shunt was detected on levo-angiographic phase of the pulmonary artery cineangiogram. Generally, small shunts became trivial and trivial shunts disappeared during follow-up. None of the patients had clinical signs suggestive of ASD, and no patient needed surgical closure during this period. In group II , on repeat transesophageal contrast echo study with Valsalva, minimal right-to-left shunt was seen initially (3 months) in two of five patients (40%), which completely disappeared at further follow-up . No patiIn group III, the single patient with CVA due to right-to-left shunt via the residual atrial defect following prior tetralogy Fallot repair had a TIA four months following ASD occlusion. This patient had surgical repair of the residual ASD as per the desire of the patient’s cardiologist. There were no fractures of the wire components of device on chest x-rays in any patient. None of the patients in any of the three groups developed bacterial endocarditis.Based on these data, the conclusion was that effective ASD closure with the buttoned device can be achieved in patients with left-to-right shunt and presumed paradoxical embolism. Modification of the device so as to place the square-shaped patch on the right atrial side may be required to avert cerebrovascular accidents and transient ischemic attacks in subjects with right-to-left shunts .In collaboration with Dr. Gautam Singh of St. Louis University, several ultrasound reviews were prepared and published ,11,12. TIn collaborative research studies with Dr. Saadeh Jureidini of St. Louis University, multiple echo-Doppler studies were performed, and these include value of innominate vein morphology in the detection of persistent left superior vena cava , echo-DoThe first of these studies concluded that absent or small left innominate vein (less than 47% of the size of the innominate artery) predicts the existence of a persistent left superior vena cava . The secDuring the evaluation of outcomes of balloon pulmonary valvuloplasty (BPV) for valvar pulmonary stenosis (PS) in 80 patients, three-to-ten-years following the procedure, echo-Doppler studies were utilized . These sBased on these data, it was concluded that the long-term results of BPV are excellent and that BPV is the management of option in the treatment of valvar PS; however, our study raises concern regarding development of PI at long-term follow-up .A number of editorials addressing echo-Doppler related subjects were contributed by the author ,19,20,21Congenitally corrected transposition of the great arteries (CCTGA) is a rare CHD. The anatomic, physiological, and clinical aspects of CCTGA with particular attention to sub-pulmonary obstruction of the morphologic LV caused by of the membranous ventricular septal aneurysm in patients with both levocardia and dextrocardia ,23,24 weWith the introduction of trans-catheter occlusion of patent ductus arteriosus (PDA), measurement of the size of the ductus has become important in the choice of the device size for implantation; angiographic minimal ductal diameter is used in the device size selection ,26,27. NForty-seven patients were taken to the cardiac catheterization laboratory with the goal to occlude the PDA during a four-year period from July 2002 to June 2006. All the patients had echo-Doppler studies in a conventional manner prior to the catheterization procedure and aortograms were procured during the cardiac catheterization. Ductal or parasternal short axis views were utilized to determine minimal ductal diameters on 2D and color-Doppler. Straight lateral view images were utilized to measure minimal ductal diameter on angiography.Thirty-one patients underwent Amplatzer Duct Occluder (ADO) occlusion of PDA, while thirteen subjects had closure with Gianturco coils. PDA occlusion could not be performed in three patients because the PDAs were very large in size (N = 2) or pulmonary vascular obstructive disease (N = 1) was present. The ages of the patients varied between 4 and 303 months; the mean was 55.4 months. The weights ranged between 3.5 kg and 77 kg, and the mean was 17.9 kg. p = 0.007) than that measured on 2D (3.99 ± 1.37 mm). Both these diameters were larger (p < 0.01) than minimal ductal diameter (2.28 ± 1.25 mm) measured by angiography. The study subjects were separated into 5 different age groups as well as into Krichenko types; the discrepancy between echo and angiographic diameters continues to exist (p < 0.05 to <0.001) for all age subgroups  and is somewhat bigger  , PDA in Characteristic echocardiographic features of important cardiac defects such as tetralogy of Fallot, transposition of the great arteries, tricuspid atresia, total anomalous pulmonary venous connection, truncus arteriosus, and hypoplastic left heart syndrome were presented. Echocardiographic images of pulmonary atresia with intact ventricular septum, double-outlet right ventricle, double-inlet left (single) ventricle, Ebstein’s anomaly of the tricuspid valve, and interrupted aortic arch were also shown. In babies without cardiorespiratory distress and a cardiac murmur, the source of murmur may be identified, whether it is a small VSD, branch pulmonary artery stenosis, mild aortic or pulmonary stenosis, or a functional murmur. It was concluded that echocardiography along with Doppler are exceedingly valuable in the assessment of the neonate with suspected and known heart disease. The PDA produces left-to-right shunt, largely in proportion to the minimal ductal diameter. In premature babies, such shunts produce pulmonary and cardiac compromise. Although the clinical features, chest x-ray, and serum brain natriuretic peptide (BNP) levels are helpful in identifying a PDA, hemodynamically significant PDAs are best detected and quantified with the help of echo-Doppler studies ,34,35. TIn small PDAs, the Minimal ductal diameter (MDD) is small and there is a high Doppler velocity across the PDA , while iLastly, in small PDAs, normal diastolic anterograde flow is seen descending aorta , while iClinicians caring for premature babies may be able to determine the size of the PDA by the evaluation of the diameter of the LA, LA:Ao ratio, the LV dimension, estimated pressures in the pulmonary artery, MDD, magnitude of Doppler flow velocity across the PDA, and flow patterns in the descending aorta . A baby Despite an excellent relationship between Doppler and catheterization gradients across obstructive lesions of the heart as we observed/reported ,37,38,39n = 30), PS (n = 24), and CoA (n = 28). Relationship between these values before and after correcting for PR was analyzed. PR was calculated on the basis of fluid dynamic-based equation utilizing echo data. The effect of geometry of the lesion on the magnitude of PR was also examined. Doppler-derived pressure gradients are regularly utilized as a substitute for catheter peak-to-peak gradients (PPGs) for recommending intervention in children with aortic stenosis (AS), PS, and coarctation of aorta (CoA). However, the Doppler gradients do not accurately predict the catheter PPGs. Consequently, misclassification of the severity of lesion may occur with frequent improper consideration for transcatheter or surgical intervention. Pressure recovery (PR) appears to account for most of the difference between Doppler-derived and catheter-measured PPGs in in vitro experimental studies and in investigations in adult subjects. However, clinically important PR in congenital AS, PS, and CoA has not been adequately investigated. Doppler-derived and catheter-measured PPGs were secured simultaneously in a prospective manner in eighty-two consecutive patients with a median age of 12.2 months and a median weight of 7.5 kg with AS (p < 0.001) than the uncorrected peak instantaneous and mean Doppler PIGs. The pressure recovery-corrected PIGs were able to predict catheter PPGs with high degree of specificity and accuracy for all lesions with 95 percent confidence limits of 36 to 97 percent and 85 to 100 percent, respectively (p < 0.05). The pressure recovery accounted for 4 to 42 percent of the overestimated catheter PPG by Doppler PIG. There was direct relationship (r = 0.33 to 0.47) to the valve area with an inverse relationship (r = −0.22 to −0.34) to downstream vessel diameter although the correlation coefficients were low. These relationships were more significant (p < 0.05) in CoA and PS patients than in AS patients. On the basis of these data, we concluded that considerable PR happens in childhood AS, PS, and CoA and this pressure recovery phenomenon accounts for misclassifying the severity of the lesion by the Doppler-derived PIG. The pressure recovery-corrected Doppler PIGs are more reliable in predicting the catheter-measured PPGs. It also appears that the magnitude PR is dependent on the geometry of stenotic lesion in children.The Doppler peak instantaneous gradient, corrected for pressure recovery, had considerably better relationship with the catheter-measured PPG (Recently, a complete manuscript was prepared and submitted for publication and the manuscript was published . The author has described echo-Doppler features of several CHDs over the years and these include, pulmonary stenosis ,44, aort


The optimal surgical strategy for the correction of double outlet right ventricle  or TGA with ventricular septal defect (VSD), pulmonary stenosis (PS), and borderline small left ventricle (LV) is still controversial. The half-turned truncal switch operation (HTTSO) introduced by Yamagishi and colleagues is a good option, but it is still challenging in a patient with borderline small LV. We aimed to describe our experience of a case of HTTSO conversion from single ventricle palliation.A 5-year-old girl with single ventricle physiology was referred to our hospital from Kazakhstan for a Fontan operation. At the time of birth, she was diagnosed with DORV (TGA type), PS, and situs inversus totalis, with moderate valvar and subvalvar stenosis and a relatively small LV cavity. Her LV volume was not adequate to support the systemic circulation; therefore, doctors in Kazakhstan selected the single ventricle palliation course of treatment for the infant. At 4 months of age, she underwent left-sided modified Blalock-Taussig shunt, patent ductus arteriosus ligation, and atrial septectomy. At 2 years of age, shunt takedown, left bidirectional cavopulmonary shunt, and main pulmonary artery division were performed. Annual echocardiography of the patient showed that the LV size was growing too adequately to persist with the single ventricle palliation course of treatment. Via a multidisciplinary approach, we considered her LV to be suitable for biventricular repair and HTTSO was planned. The operation and postoperative course were uneventful. The patient was discharged on postoperative day 6 and went back to Kazakhstan.Based on our successful surgical outcome, in patients diagnosed with DORV (TGA type) or TGA with VSD, PS, and borderline LV, HTTSO after achieving adequate LV growth by single ventricle palliation may be considered a good alternative to conventional operations in patients at a high risk for initial biventricular repair. The half-turned truncal switch operation (HTTSO) was first reported by Yamagishi and colleagues in 2003 as an alternative to the Rastelli, the Lecompte, and the Nikaidoh procedures for patients with double outlet right ventricle  or TGA with ventricular septal defect (VSD), and pulmonary stenosis (PS) , 2. The Although the HTTSO is still challenging in patients with borderline small left ventricle (LV), it could be a treatment of choice after single ventricle palliation with adequate LV growth. We aimed to describe our experience of a case of HTTSO conversion from single ventricle palliation.A 5-year-old girl weighing 17.4 kg who had single ventricle physiology was referred to our hospital from Kazakhstan for a Fontan operation. She was diagnosed in her country with DORV (TGA type), PS, and situs inversus totalis. At the time of her birth, her pulmonary valve and LV were not adequate to support the systemic circulation because of moderate valvar and subvalvar stenosis and a relatively small LV cavity. Therefore, the doctors in Kazakhstan selected the single ventricle palliation course of treatment for the infant. At 4 months of age, she underwent a left-sided modified Blalock-Taussig shunt, patent ductus arteriosus ligation, and atrial septectomy performed by a local medical team in Kazakhstan. At 2 years of age, shunt takedown, left bidirectional cavopulmonary shunt (BCPS), and main pulmonary artery (PA) division were performed in Kazakhstan by our medical team volunteers who visited Kazakhstan every year to follow up on the patient. Annual echocardiography of the patient showed that the LV size was growing too adequately to persist with the single ventricle palliation course of treatment. We thought that the patient might be able to undergo biventricular repair, but precise examinations, such as computed tomography angiography with 3-dimensional reconstruction, and a multidisciplinary approach were required. We decided to invite her to our hospital in South Korea and formulated the next management plan for her.2, respectively. The mitral valve Z-score was − 1.76, and the mitral valve/tricuspid valve ratio was 0.87. The LV ejection fraction obtained using the Simpson method was 59.2%. A computed tomography angiography scan showed the same anatomical results with echocardiography  or TGA with VSD, and PS is still controversial. This is especially true if the LV volume is not adequate to support the systemic circulation during the neonatal period.Patients with mild LV hypoplasia may be amenable to eventual biventricular repair; however, they are at a higher risk if such a strategy is followed, particularly in infancy. Moreover, single ventricle palliation in a patient with two ventricles that are potentially adequate for biventricular repair can unnecessarily subject the patient to comorbidities related to the Fontan physiology , 5. EmanThe common concept of BCPS is to relieve the source of volume and/or pressure load on the LV, and the ability of the LV to sustain a systemic function begins to decrease. However, since the volume and/or pressure load on the LV is not completely eliminated, the remaining blood flow might be able to mediate the growth of borderline LV with or without the LV recruitment strategy. Initially, in our patient, training the LV was not part of the treatment plan, but it was unintentionally trained or rehabilitated during the treatment course. The patient had relatively a large VSD, and BCPS as single ventricle palliation might have modified the LV ability. It gave us an excellent experience and awareness to consider biventricular repair of borderline LV in patients with single ventricle palliation.The conventional approach to anatomic surgical repair in patients with DORV (TGA type) or TGA with VSD, and PS is the Rastelli or Lecompte procedure. However, these procedures have several serious drawbacks related to an earlier need for reinterventions or reoperation of the RVOT and a higher incidence of subaortic tunnel obstruction , 9. To oIn patients diagnosed with DORV (TGA type) or TGA with VSD, PS, and borderline LV, HTTSO after LV growth by single ventricle palliation is a good alternative to conventional operations in patients at a high risk for initial biventricular repair.


The purpose of the present trial is to determine whether opening co-existing chronic total occlusions (CTOs) using percutaneous coronary interventions (PCIs) improves cardiac function in patients with multi-vessel disease (MVD). Patients with MVD are defined as having at least one additional major vessel exhibiting no less than 75% stenosis combined with the presence of a CTO artery.Patients will be prospectively recruited who meet the following criteria:(1)angiographically diagnosed with MVD concurrent with CTO;(2)previously diagnosed with myocardial infarction, or suffered myocardial necrosis of the CTO-territory determined using cardiovascular magnetic resonance (CMR).Patients presenting with no necrosis of myocardial tissue in the territory of the CTO will be excluded. Recruited patients will be randomized into 2 groups: those undergoing PCI of only the non-CTO artery (non-CTO PCI group), and those undergoing PCI of the non-CTO artery concurrently with the CTO artery (CTO-PCI group). The primary outcome will be the change in cardiac function evaluated via CMR at a 12-month of follow-up appointment, which will be compared to a baseline measurement. Secondary outcomes include occurrence of major cardiac events, CMR-assessed myocardial viability in the CTO-supplied territory, and quality of life assessed by Seattle angina questionnaire, Patient Health Questionnaire 9 and Generalized Anxiety Disorder Scale-7 after 12-month follow-up.The SOS-moral trial will provide data necessary to determine whether to open concurrent CTOs among MVD patients with CMR-detected necrotic myocardial tissue. The difference was most significant in young patients and those with acute ST-segment elevated myocardial infarction (STEMI). Another study found that ischemic cardiac dysfunction was associated with increased mortality among patients with CTO lesions within the first 1 to 2 years of identification of the disease. Percutaneous coronary intervention (PCI) for CTO is performed to relieve symptoms, improve cardiac function, decrease the need for subsequent coronary artery bypass graft (CABG), and improve quality of life (QOL).A chronic total occlusion (CTO) is defined as a coronary artery occlusion for a period ≥3 months, which can be detected by angiogram.–12 However, another study could not demonstrate benefits of CTO-PCI when assessing the occurrence of major adverse cardiac events (MACE); among patients with CTO of a single coronary artery, PCI did not reduce cardiac mortality and MACE when compared to optimal medical therapy (OMT). The prospective, open-labeled, randomized DECISION-CTO trial revealed that OMT as an initial strategy was non-inferior to PCI with regard to the composite endpoint of death, MI, stroke, or any revascularization within a 3-year follow-up period. A multicenter, open-labeled, randomized, controlled EuroCTO trial showed that PCI for CTO resulted in a significant improvement of health status compared with OMT alone, rather than resulting in the reduction of MACE.Previous studies revealed that for both CTO of a single coronary artery and MVD with concurrent CTO, even with well-developed collateral circulation, successful CTO-PCI is associated with reduced long-term cardiac mortality and reduced need for CABG, which is an advantage that can persist 2 to 5 years following PCI. Hence, the effect of CTO-PCI on cardiac function merits investigation. An early study that recruited patients with at least 1 CTO and a LVEF of ≤ 40% found that CTO-PCI decreased left ventricular end-systolic volume and increased LVEF. Another study, with a small sample size, showed that successful CTO-PCI improved regional wall motion. The EXPLORE trial showed that routine CTO-PCI did not result in an overall benefit with respect to LVEF and lower left ventricular end-diastolic volume (LVEDV) within 4 months, when compared with a non-CTO PCI strategy in an unselected cohort of patients with STEMI and concurrent CTO. An extended examination of the EXPLORE trial also did not reveal beneficial effects associated with routine early CTO-PCI on LVEF within a 1-year period.The presence of a CTO and not MVD alone has been reported to be independently associated with long-term mortality and impaired left ventricular eject fraction (LVEF).Myocardial viability affects CTO-PCI outcomes. With respect to myocardial viability, the myocardium in the CTO territory can be divided into groups as follows: complete survival, partial survival, and non-viable myocardium. We predict that conflicting conclusions drawn by previous studies can be partially attributed to the failure to consider the status of myocardial tissue or the burden of ischemia.At present, US and European guidelines provide Class IIa or IIb recommendations for PCI for the treatment of CTO. The recommendation comes despite the fact that the rate of successful CTO-PCI is more than 90% at experienced centers and can be increased by training of operators working within clinical practices, especially those in small centers. These facilities include a large portion of patients presenting with CTO combined with MVD who receive treatment involving exclusively non-CTO PCI or incomplete revascularization. The purpose of the present trial is to compare the effect of CTO-PCI combined with non-CTO PCI versus non-CTO PCI with respect to cardiac function, myocardial viability, and MACE among patients with MVD and necrotic myocardial tissue. Cardiovascular magnetic resonance (CMR) will be used to assess the viability of the myocardium, which facilitates identification of patients who will benefit from complete revascularization procedures.22.1This SOS-moral study is a randomized controlled trial with a multi-center design. The protocol was approved by the ethics committee of Beijing Anzhen Hospital  and has been registered at ClinicalTrials.gov (identifier: NCT 03372785).Patients meeting the inclusion criteria will be categorized into two groups at a ratio of 1:1 according to a randomized digital table used to randomly assign patients to the CTO-PCI group (PCI of both the non-CTO artery and a concurrent CTO artery), or the non-CTO PCI group (PCI of only the non-CTO artery). The randomized digital form and interactive voice response mode will be applied to facilitate the randomization procedure. The randomization sequence will be produced and managed by an independent staff member. Before intervention, myocardial viability and cardiac function of patients will be evaluated using CMR. Cardiac function will be assessed using transthoracic echocardiography and CMR. The Seattle angina questionnaire (SAQ), Patient Health Questionnaire 9 and Generalized Anxiety Disorder Scale-7 will be used to evaluate patient QOL. Cardiac function, QQL, and MACE will be observed within 12 months of follow-up. A flow chart outlining the study design is depicted in Figure 2.2Patients in the CTO-PCI group receive PCI treatment involving both the CTO artery and the non-CTO artery. Patients of the non-CTO PCI group will only have PCI performed on the non-CTO artery. To ensure safety of all patients, they will be monitored, and those with persisting clinical symptoms occurring within one month of OMT will undergo PCI of CTO artery.2.3We will enroll patients hospitalized for stable or unstable angina pectoris in Beijing Anzhen Hospital, The First Affiliated Hospital of Dalian Medical University and Beijing Friendship Hospital from April of 2018 to December of 2021 meeting the selection criteria. All subjects/guardians enrolled in the trial should clearly understand the research requirements and intervention procedures, and each will be required to sign a written informed consent agreement before participating in any type of examination or intervention. All participating research centers should obtain all informed consent forms from patients before the initiation of intervention. Personal information will be kept confidential before, during, and after the trial.2.3.1To meet inclusion criteria, patients should: be 18 to 80 years old; be diagnosed with single CTO concurrent with MVD detected using coronary angiography (at least one other major vessel should have exhibited no less than 75% stenosis); previously have been diagnosed with myocardial infarction, or suffer from myocardial necrosis in the territory of CTO artery determined by CMR; present with an LVEF above 35% determined using transthoracic echocardiography; present with CTO located in an epicardial coronary artery with a reference diameter of ≥ 2.5 mm; and comply with all the evaluations and follow-up protocols.2.3.29/L or > 700 × 109/L and white blood cell counts < 3 × 109/L; with active bleeding or bleeding tendencies ; severe coexisting conditions, including severe renal function dysfunction , severe heart failure (NYHA classification III–IV), acute infectious diseases and immune disorders; tumors; surgery within 3 months; a life expectancy less than 12 months; pregnancy or planning to become pregnant; history of allergy or adverse reactions to aspirin, clopidogrel, ticagrelor, stains, contrast material, anticoagulant, or stents. Patients will also be excluded if they cannot tolerate dual antiplatelet treatment; are unable to communicate due to cognitive impairment, auditory, or visual impairment; are participating in another trial for medication or an apparatus and in which the main endpoint has not been reached, or plan to participate in a clinical trial within 12 months of the intervention.Patients will be excluded if they have suffered from acute myocardial infarction within the previous 3 months; a lesion located in the left main artery (stenosis ≥50%); rheumatic valvular disease; severe arrhythmia; a history of revascularization within the non-CTO artery; multiple vessels with CTO (more than one CTO artery); lesions unsuitable for PCI; severely abnormal hematopoietic systems, such as platelet counts <100 × 102.42.4.1Experienced operators have been designated to ensure that the success rate of CTO-PCI is above 80%. Procedural success is defined as resulting in residual stenosis of <10% with thrombolysis in myocardial infarction grade 3 flow, in the absence of dissection and thrombosis. The use of a DES and specialized devices will be left to the discretion of the operator.2.4.2Patients included in both CTO-PCI group and non-CTO PCI group will be administered aspirin (300 mg) and one P2Y12 receptor antagonist (300–600 mg clopidogrel or 180 mg ticagrelor) before PCI unless they have been treated with these antiplatelet agents previously. Calcium antagonists, nitrates, sodium nitroprusside, and GP IIb/IIIa receptor antagonists will be prepared and administered in any case in which no-reflow occurs in the PCI procedure. After PCI, all patients will be routinely administered one P2Y12 receptor antagonist (clopidogrel 75 mg/d or ticagrelor 90 mg twice daily), aspirin (100 mg/d) and statin once daily for 12 months. Other medications such as beta-blockers, calcium antagonists, and nitrates will be administered according to the clinical status of each patient, considering factors such as heart rate, blood pressure, and cardiac function.2.52.5.1CMR will be performed using a Siemens 3.0T whole-body MR scanner . A 32-element matrix coil will be utilized for data collection, and electrocardiographic gating will be utilized to acquire all sequences. First, the morphologic data from the heart will be acquired with the short-axis plane (from the base to the apex) and long-axis plane of the left ventricle (LV). Next, 0.05 mmol/kg Magnevist contrast agent will be injected intravenously with a high-pressure syringe at 5 mL/s. The first-pass perfusion image (8-mm sections with no intersection gap) will be acquired when magnevist is injected. LGE imaging (8-mm sections with no intersection gap) will be acquired 10 minutes after the intravenous administration of gadolinium  using a 2-dimensional, phase-sensitive, inversion-recovery, breath-hold sequence.CMR will be utilized to assess myocardial infarct size, left ventricular mass, LVEF, LVEDV, left ventricular end-systolic volume (LVESV), cardiac output, stroke volume, segmental wall thickening, and myocardial viability in the territory supplied by the artery with CTO.2.5.2Transthoracic echocardiography (Philips ie33 GE vivid 7) will be utilized to determine left ventricular end diastolic diameter, left ventricular end systolic diameter, LVEF, and segmental wall thickening.2.6Patients will be followed-up via outpatient consultation 1, 6, and 12 months following PCI. A follow-up appointment 12-months post-PCI will be conducted at the hospital. Basic characteristics including gender, BMI, waist circumference, comorbidities, medication history, blood pressure, and heart rhythm both at baseline and 1-year post-PCI will be documented by an independent physician. Blood tests assessing routine blood counts, liver and kidney function, blood lipid profiles, fasting blood glucose, glycosylated hemoglobin, hsCRP, and BNP will be recorded at baseline (before angiography) and at 1-year post-PCI. CK, CK-MB, and cTNI levels will be collected at baseline, one day after intervention, one week after intervention, and at 1-year post-PCI.2.6.1The primary endpoint of this SOS-moral study will be difference in cardiac function observed between baseline and 1-year post-intervention, which will be determined by CMR and transthoracic echocardiography.2.6.2Secondary endpoints involve the occurrence of MACEs, defined as all-cause mortality, cardiac death, a first or recurrent, non-fatal, acute myocardial infarction, target lesion revascularization (PCI or CABG), stroke, heart failure and cardiac rehospitalization within 1, 6, and 12 months post-PCI. Other secondary endpoint will include changes in myocardial viability in the territory supplied by the CTO artery between the baseline and 12 months post-PCI, to be determined by CMR. In addition, QOL changes at 1, 6, and 12-month follow-up appointments will be assessed by comparing with baseline values using the SAQ, patient health questionnaire 9 and Generalized Anxiety Disorder Scale -7. Finally, the volume of contrast used during the procedure and the total cost of medical care covering OMT and the equipment for coronary artery disease therapy from the day of enrollment  to the last follow-up  will be evaluated. Perioperative myocardial infarction will be evaluated by assessing CK, CK-MB, and cTNI levels;2.6.3The safety of the perioperative period, including acute coronary artery occlusion, acute vascular perforation, acute stent thrombosis, acute myocardial infarction, and cardiac death of the two groups assessed, will be compared.2.7 Two-hundred sixteen cases recruited to the study will allow for the use of a 1-tailed test with a significance level (α) set to 0.025, and power (1-β) of 0.90. Ultimately, it is estimated that 240 patients will be randomized, and a 10% loss is expected to occur throughout the 1-year follow-up period.PASS 15.0 will be utilized to calculate sample size. In the study, 226 individuals are predicted to be recruited in the trial. This sample size was calculated using the optimal efficiency test. The main purpose of this trial is to investigate the effect successfully opening concurrent CTO lesions on cardiac function in patients with MVD. LVEF has been taken into consideration for the calculation of sample size. Previous studies revealed a 6.5% mean difference between the two experimental groups and a 9% standard deviation with respect to LVEF. The optimal boundary value for LVEF was set to 4%.2.8In the full analysis set, all randomized patients will be kept in the treatment group to which they were originally randomized. Moreover, patients without protocol deviation will be included in the per protocol set. Patients of the per protocol set will be included in baseline information analysis rather than in primary analysis if the CTO-PCI fails. Patients will not be included in the primary analysis if the MACEs occur.t-test will be used to make comparisons between two independent samples. Median and 4-quintile intervals will be used to express variables that are not normally distributed, and the Mann–Whitney U-test will be used to compare differences. Categorical variables will be presented as frequencies and percentages, and the differences between groups will be assessed using a chi-square test. Survival analysis will be performed using a Kaplan–Meier curve and Cox regression analysis. A 2-sided P-value < .05 will be considered statistically significant.Continuous variables normally distributed will be presented as means ± standard deviation, and student 2.9Inclusion and exclusion criteria will be enforced strictly to minimize the potential for the inclusion of confounders. An experienced cardiovascular interventionist (CTO-PCI >50 cases/yr) has been designated to ensure that the success rate of CTO-PCI is above 80%. The number PCI performed within each of the centers participating in this study is least 3,000 cases. An expert committee has been established to ensure interventional safety and prevent study-associated complications. At least two senior experts in PCI (PCI >3000 cases per year) will assist to discern MACEs throughout the follow-up period. Two experienced specialists will acquire CMR images and collect data using specific equipment and software. Two independent investigators will be responsible for the creation of protocols and supervising follow up, and they will communicate with the enrolled participants throughout follow-up. The case report form will be completed by independent investigators. All data obtained will be documented in the database by two independent investigators according to guidelines governing data management. A special inspector will be responsible for tracking, monitoring and reviewing the research process, and it will not be possible to alter data at will. The database will be inactive after cross validation, followed by statistical analysis. The staff that perform analysis will be blinded to the intervention.3,10 however, there remains a lack of evidence from a randomized control trial, which can be sued to conclusively determine whether the success of opening concurrent CTO lesions improves cardiac function among patients presenting with MVD but not STEMI.This trial aims to investigate the effect of CTO-PCI combined with non-CTO PCI on cardiac function in patients with MVD. Patients with MVD in a EuroCTO trial received non-CTO PCI before randomization; participants in the DECISION-CTO trial were not limited to those with MVD; the EXPLORE study recruited patients with STEMI. Consequently, a number of studies have investigated the clinical effects of successful CTO-PCI;–25 An early meta-analysis found that successful recanalization of a CTO resulted in an overall improvement of 4.44% absolute LVEF points, reduced remodeling, and improved survival (OR: 0.52). However, the EXPLORE trial showed that in acute STEMI patients with concurrent CTO, CTO-PCI did not increase global LVEF or decrease LVEDV assessed by CMR 4-month post-PCI compared to patients receiving treatment in the non-CTO artery. Interestingly, a subgroup analysis of the EXPLORE trial showed that CTO-PCI in patients with a concurrent CTO in the LAD was associated with significantly higher LVEF levels after 4-month post-PCI compared with non-CTO PCI, suggesting that CTO-PCI may potentially benefit high-risk patients. According to Chung, the benefit of CTO-PCI is controversial with respect to cardiac function and survival among the MVD patients with concurrent CTO. This may partly be because myocardial viability affects the alteration of cardiac function produced by CTO-PCI. An in-depth analysis in the EXPLORE CMR study revealed that CTO-PCI was associated with the greater recovery of regional systolic function relative to baseline values 4-month post PCI in dysfunctional myocardial tissue supplied via CTO. The benefit was most evident in dysfunctional but viable segments . The investigators opined that the benefit was probably attributable to the recovery of stunned myocardial tissue affected by the acute interruption of blood supply, as well as by the prevention of arrhythmia. Taken together, the data suggest that varying levels of myocardial viability in patients included in previous studies may be associated with reported variations in cardiac functioning observed after successful CTO-PCI treatments. Therefore, myocardial viability should be considered.Early studies reported that successful recanalization CTO can both improve LVEF and ventricular wall movement assessed by CMR, and can improve QOL. Differences in myocardial viability may contribute to the variable prognosis of CTO-PCI. A previous study including 32 CTO patients presenting with significant inducible perfusion deficits found that recanalization was associated with decreased ischemic burden, improved QOL, and reversed remodeling. The effect of CTO-PCI on cardiac function among patients with necrotic myocardial tissue in the territory supplied by the CTO combined with MVD requires further investigation. The present SOS-moral study excludes those patients with complete myocardial survival in the CTO artery territory. This distinction will facilitate the investigation of the effects of actively opening concurrent CTO lesion in MVD patients with necrotic myocardial tissue identified via CMR in the territory supplied by the CTO, aiming to provide reliable evidence for use in clinical practice.Previously, 128 patients were observed using CMR, and among the myocardial regions that corresponded to 149 CTO lesions, only 11.5% presented as transmural myocardial infarction. In fact, 58.6% of the myocardial segments showed no delayed enhancement. CMR has been used to assess myocardial viability throughout the previous decade. According to Cardona et al., CMR accurately detects myocardial viability in patients with reduced LVEF. We previously demonstrated that, using PET as gold standard, CMR has high consistency, sensitivity, and specificity for the detection of myocardial viability compared with PET in CTO patients. Therefore, in the SOS-moral trial, CMR will be used to evaluate both the amount of viable myocardial tissue and level of cardiac functioning.CMR is an appropriate approach for the evaluation myocardial viability and cardiac function. The method is accurate, safe, and provides great spatial resolution as well as sensitivity.4SOS-moral will sort myocardial viability before randomization to avoid the effect of viability of myocardial on cardiac function. Hence, the real benefits of CTO-PCI on cardiac function among these patients without 100% survival viable myocardial will be assessed. Furthermore, the present trial strictly recruits patients with MVD and concurrent CTO. SOS-moral will provide evidence for the value of CTO-PCI among these selected patients. Nevertheless, there remain several potential limitations in this study. First, SAQ may be affected by factors other than recanalization of CTO artery during the study period. Second, patients with high risk such as those with left main artery disease stenosis ≥50% and severe arrhythmia are not included. Patients with left main artery disease are not eligible because the PCI procedure needs to be individualized. Because cardiac function might be affected by the severe arrhythmia, those with severe arrhythmia will be excluded. Therefore, the outcomes are unable to include all patients at high risk. Third, in a limited study period, the study may be not powered to detected MACE differences between the two groups. Therefore, further studies including high-risk patients and with longer follow-up periods are needed in the future.The authors wish to thank Ya Yang and Yueli Wang for their contribution in performing transthoracic echocardiography. The authors highly thank for Wenyi Zhang and Haoran Xing, who help recruit patients. We gratefully acknowledge Jiahui Li for performing follow-up evaluations of patients, as well as Xin Zhao and Nan Nan for collecting data. The authors also wish to thank the patients who participated in the study and staff from the 3 centers who supported the study.Xiantao Song and Rongchong Huang contributed to the study design. Jinfan Tian and Dongfeng Zhang contributed to draft the manuscript. Xueyao Yang contributes to the patients’ follow-up. Minduo Zhang and Yuan Zhou perform the intervention implementation and patients’ recruitment. Lijun Zhang contributes to CMR perform. Yi He and Hongzhi Mi help to CMR technology supervision. Huijuan Zuo contribute to the data monitor. Xiantao Song and Min Zhang contribute to the endopoint adjudication.Conceptualization: Xiantao Song and Rongchong Huang.Data monitor: Huijuan Zuo.Date management: Jinfan Tian and Dongfeng Zhang.Endpoint adjudication: Xiantao Song and Min Zhang.Investigation: Xueyao Yang, Minduo Zhang and Yuan Zhou.Technology supervision: Yi He and Hongzhi Mi.


Galinier Never let a ‘good’ crisis go to waste!(attributed by some to Winston Churchill on planningto set up the United Nations during World War II)et al.In this issue of the Journal, Galinier P = 0.80), and for all pre‐specified secondary endpoints. A further analysis, focussing on first unplanned hospitalisation for heart failure, suggested a modest improvement , that was driven by larger effects in those who weighed themselves regularly or had greater functional limitation or who were more socially isolated. Some will view this trial as further evidence that home telemonitoring is ineffective for heart failure, ignoring the overall positive effect identified by systematic reviews.The trial was neutral for its composite primary endpoint, unplanned hospitalisation for heart failure or all‐cause mortality  that should be grasped.Many trials of telemonitoring for heart failure have attempted to predict and manage episodes of decompensation; this ‘crisis management’ strategy has produced inconclusive results.TableTelemonitoring should be time efficient. Dentists recommend that people should spend at least 2 min twice a day brushing their teeth. A cardiovascular health check takes less time. Daily checks are probably not required for stable patients; text reminders can be scheduled less often. The focus should be on acquiring therapeutically actionable data, such as symptoms, heart rate and rhythm, weight, or more sophisticated measurements of congestion if available Table1. PulsThere are other important consequences of switching from a traditional model of care. Home telemonitoring enables patients to be part of the workforce, delivering truly individualised healthcare.In summary, adoption of home telemonitoring as a routine clinical service for most medical problems will improve the efficiency and quality of care, reduce demands on patients, and reduce healthcare costs and environmental pollution. It will also reduce the spread of infections, whether that is the misery of seasonal rhinovirus, annual influenza, or a lethal pandemic. Let's do it—now!SCI is supported by a Future Leader Fellowship, Heart Foundation of Australia.Conflict of interest: J.G.F.C. has received honoraria from Abbott, Medtronic and Philips for advisory boards. All other authors report no conflicts of interest.


Coronary collateral circulation and conditioning fromremote ischemic coronary territories may protect culprit myocardium in theelderly, and younger STEMI patients could suffer from larger infarcts. Weevaluated the impact of age on myocardial salvage and long-term prognosis in acontemporary STEMI cohort.Of 1603 included STEMI patients 807 underwent cardiacmagnetic resonance. To assess the impact of age on infarct size and leftventricular ejection fraction (LVEF) as well as the composite endpoint of deathand re-hospitalization for heart failure we stratified the patients by an agecut-off of 60 years.Younger STEMI patients had smaller final infarcts  and higher final LVEF . Afteradjusting for multiple potential confounders age did not remain significantlyassociated with infarct size and LVEF. During 4-year follow-up, the compositeendpoint occurred less often in the young  with aunivariate hazard ratio of 5.77 . Eventestimates of 4 subgroups (young vs. elderly and infarct size beyond vs. belowmedian) showed a gradual increase in the occurrence of the composite endpointdepending on both age and acute infarct size (log-rankp < 0.001).Having a STEMI after entering the seventh decade of lifemore than quadrupled the risk of future death or re-hospitalization for heartfailure. Risk of death and re-hospitalization depended on both advanced age andinfarct size, albeit no substantial difference was found in infarct size, LVEFand salvage potential between younger and elderly patients withSTEMI. Exclusion criteria for CMR were potential pregnancy, known contrastallergy, severely impaired kidney function, atrial fibrillation/flutter orpacemaker or cerebral/cochlear implants.www.clinicaltrials.gov under NCT01435408 (DANAMI 3-iPOSTand DANAMI 3-DEFER) and NCT01960933 (DANAMI 3-PRIMULTI).Patients were included after written informed consent andthe national ethical committee approved the study. The study was performedin accordance with the Helsinki declaration. The DANAMI-3-trial program wasregistered on 3In this DANAMI-3-trial substudy, we evaluated the impact of ageon patients with STEMI with available CMR (n = 807) for imaging endpoints andthe entire population included at Rigshospitalet (n = 1603) for clinicaloutcome. For the status “elderly” no universally acknowledged age cut-off existsbut World Health Organisation suggests 60 to 65 in developed countries4CMR was performed after primary PCI both during index admission(CMR index) and after 3 months (CMR follow-up). Both index and follow-up CMRexaminations were performed on a 1.5 Tesla scanner using a 6-channel body array coil. Scout images as well as 2-, 3- and 4-chamberimages were used to setup the short axis image plane. CMR index scan assessedarea at risk, acute infarct size, MVO and left ventricular (LV) ejectionfraction (EF). CMR follow-up scan assessed final infarct size and final LVEF.Area at risk was assessed using a T2-weighted short tau inversion-recoverysequence. Acute and final infarct size were assessed using delayed contrastenhanced electrocardiogram-triggered inversion-recovery imaging afterintravenous injection of 0.1 mmol/kg body weight gadolinium-based contrast. The inversion time was continuouslyadjusted to null the signal from the normal myocardium. Acute and follow-up LVEFwere derived from steady state free precession cine imaging. All images wereobtained in the short-axis plane with 8 mm slice thickness and 0 mm slice gap,covering the entire LV.5CVI42  wasused for all quantitative analyses and performed by a reader blinded to allclinical and paraclinical data. A second blinded reader reviewed all analyses,and any relevant discrepancy was discussed and if necessary, adjusted untilconsensus was reached. On T2-weighted images area at risk was defined ashyperenhanced myocardium at a threshold of remote myocardium mean signalintensity ≥ 2 standard deviations (SD). Infarct size was identified as delayedgadolinium enhanced area with a threshold of remote myocardium mean signalintensity ≥ 5 SD 5.1t test orWilcoxon rank-sum test as appropriate. Qualitative variables were summarizedby counts and percentages and compared with the chi-square test. Apopulation division was made with age of 60 years as cut-off. Differences intime to event distributions were assessed by means of the log-rank test, andthe Kaplan-Meier method was used to display event free survivalprobabilities. Clinical outcomes were examined with time-to-first-eventanalysis. We used Cox proportional hazards regression models to calculatehazard ratios with 95% confidence intervals (CI) and adjusted for variablesthat were significantly different between the groups, as well as potentialconfounders: multivessel disease; thrombolysis in myocardial infarction(TIMI) flow 0/1 pre-PCI; Killip class at admission; anterior STEMI location;time from symptom onset to balloon; diabetes; hypertension; family historyof coronary artery disease; current smoking; troponin T peak value andgender. The assumption for the proportional hazards was found tenable byexploration of log  curves and by testing the interactionterm of each covariate with survival time. With linear regression weevaluated the association between age and infarct size as well as age andLVEF. In the linear regression models we adjusted for both risk-factors andoutcome-predictors . Using analysis of covariance, we tested forinteraction between age and treatment  on the effect on acute infarct size. Atwo-sided probability value of 0.05 was the threshold for statisticalsignificance. All statistical analyses were performed with SPSS softwareversion 25.0 .Quantitative variables were tested for normality(Shapiro-Wilks test) described as mean with SD or median with interquartilerange (IQR) and compared using student’s 6A total of 1603 STEMI patients were included from the DANAMI-3trial at Rigshospitalet. 753 patients were under 60 years of age (47%) and 850patients were 60 years or above (53%). 7The median follow-up time was 40 months . Asillustrated in 8CMR examinations were available in 807 patients 50.4%; during i9With linear regression, we evaluated the importance of age,stratified by the aforementioned 60 years cut-off, and infarct size stratifiedby the median on outcomes using the Kaplan Meier method. The composite endpointof all-cause mortality depended on both age and infarct size with increasing ageand infarct size resulting in higher rates of death and heart failurere-hospitalization .Divan Gabriel Topal: Data curation, Formalanalysis, Funding acquisition, Investigation, Methodology, Projectadministration, Resources, Supervision, Validation, Visualization, Writing -original draft, Writing - review & editing. Kiril AleksovAhtarovski: Data curation, Formal analysis, Investigation,Methodology, Project administration, Resources, Supervision, Validation,Visualization, Writing - original draft, Writing - review & editing.Jacob Lønborg: Funding acquisition, Investigation,Methodology, Validation, Visualization, Writing - review & editing.Dan Høfsten: Investigation, Methodology, Resources,Visualization, Writing - review & editing. LarsNepper-Christensen: Investigation, Methodology, Resources,Visualization, Writing - review & editing. Kasper Kyhl:Investigation, Methodology, Resources, Visualization, Writing - review &editing. Mikkel Schoos: Investigation, Methodology,Resources, Visualization, Writing - review & editing. AliGhotbi: Investigation, Methodology, Resources, Visualization,Writing - review & editing. Christoffer Göransson:Investigation, Methodology, Resources, Visualization, Writing - review &editing. Litten Bertelsen: Investigation, Methodology,Resources, Visualization, Writing - review & editing. LeneHolmvang: Investigation, Methodology, Resources, Visualization,Writing - review & editing. Steffen Helqvist:Investigation, Methodology, Resources, Visualization, Writing - review &editing. Frants Pedersen: Investigation, Methodology,Resources, Visualization, Writing - review & editing. RenateSchnabel: Investigation, Methodology, Resources, Visualization,Writing - review & editing. Lars Køber: Investigation,Methodology, Resources, Visualization, Writing - review & editing.Henning Kelbæk: Investigation, Methodology, Resources,Visualization, Writing - review & editing. NielsVejlstrup: Investigation, Methodology, Resources, Visualization,Writing - review & editing. Thomas Engstrøm: Fundingacquisition, Investigation, Methodology, Supervision, Validation, Visualization,Writing - review & editing. Peter Clemmensen:Investigation, Methodology, Supervision, Validation, Visualization, Writing -review & editing.The authors declare that they have no known competing financialinterests or personal relationships that could have appeared to influence the workreported in this paper.