Long-term mechanical circulatory support is a life-saving technology while briding to heart transplantation. It increases the quality of life and preserves end-organ function for patients with advanced heart failure. The number of patients with advanced heart failure scheduled for heart transplantation before comorbidities escalate is on the rise. However, the device function is complicated by the bleeding-thrombosis and infection paradigm, hence the interest in understanding device thrombosis and infection. We describe a 27-year-old man with idiopathic cardiomyopathy, advanced end-organ failure, and severe infection, who was bridged to heart transplantation after 8 months on the Berlin Heart EXCOR  biventricular support. The patient was discharged from the hospital in the third postoperative week after the recovery of his end-organ functions. At 29 months’ post-transplantation follow-up, his last cardiac biopsy was grade 0, his ejection fraction was 60%, and he was enjoying a good quality of life. The hepatic and renal functions are important for the survival of the patient after heart transplantation. Advanced hepatic and kidney failure compromises the survival of the patient and the success of the heart transplantation.The most complicated adverse events are infection and bleeding-thrombosis with long-term use of big pulsatile pumps. Infection and thrombogenic complications may cause pump failure and malfunction, which needs the explantation of the pump or even re-implantation of a new pump for bridging to heart transplantation.3 Various dressing techniques, education of the patient and caregivers, and application of topical antibiotic solutions to the wound area may help to localize the infection.Destination left ventricular assist device (LVAD) therapy may become available in the future as an alternative to heart transplantation. Infectious complications at present, especially in the externally driven LVAD, right ventricular assist device, and biventricular assist device, have been the major cause of morbidity and mortality in mechanically supported patients. Factors such as critical status, driveline exit site, and pocket infection may result in an ascending bacterial colonization.We describe a 27-year-old man with idiopathic cardiomyopathy, advanced end-organ failure, and severe infection who was bridged to heart transplantation after 8 months on the Berlin Heart EXCOR  biventricular support.A 27-year-old man was admitted to another hospital with shortness of breath, dyspnea, and cough in May 2011. His echocardiographic studies documented dilated cardiomyopathy and ejection fraction (EF) of 15%. Mid August 2011, he was hemodynamically unstable and was in New York Heart Association (NYHA) class III-IV. The liver enzymes were elevated due to congestive cardiomyopathy. He was defibrillated 5 times, had cardiac resuscitation, and was intubated. After extubation, he was transferred to our hospital for further treatment in September 2011. 2, cardiac output of 2.74 lt/min, right ventricular stroke work index of 3 gm-m/m2/beat, and pulmonary vascular resistance of 145 dyn.s/cm5. He underwent implantable cardioverter defibrillator implantation. His elevated liver enzymes were due to ischemic hepatitis, for which he was followed up by the gastroenterology department. He was discharged from the hospital with maximum medical heart failure therapy.The patient had hepatomegaly, splenomegaly, and ascites on admission to our hospital. His echocardiographic studies demonstrated EF of 15%, systolic pulmonary artery pressure of 49 mmHg, left ventricular end-diastolic diameter of 6.6 cm, and left ventricular end-systolic diameter of 5.5 cm. Cardiac catheterization revealed pulmonary capillary wedge pressure of 28 mmHg, cardiac index of 1.4 lt/min/mStaphylococcus aureus (MSSA). Treatment was commenced with Vancomycin and Rifampicin for more than 15 days. Driveline dressing was done separately for each driveline, and the debridement and curettage of the wound was performed before the application of a local antibiotic solution. The blood cultures were reported as Staphylococcus aureus and Candida species. He received anti-Candida medication until his blood cultures were reported negative. His lower sternal incision was tender, and purulent drainage was leaking from his driveline exit sites. It was decided to apply negative pressure wound therapy using the vacuum-assisted closure (VAC) method . The VAC therapy dressing was changed every 3 days, and each driveline dressing was done separately with a topical antibiotic solution (One month later (October 2011), the patient was re-admitted to our hospital with decompensated heart failure. His liver enzymes and bilirubin levels were elevated 5 and, 8 times above the normal values, respectively. His renal function was deteriorated, and his urine output was < 30 cc/hr. He had both right and left advanced heart failure as well as end-organ dysfunctions. The patient was hospitalized in the Intensive Care Unit, where he was administered multidose inotropic medication. We deemed it advisable that he be listed as Status 1A while waiting for heart transplantation so that he could receive mechanical circulation support. He underwent the implantation of a Berlin Heart EXCOR  biventricular assist device in December 2012. He was extubated on the 3rd postoperative day owing to multiple organ failure and transferred to the cardiac surgery service on the 7th postoperative day. His renal and hepatic functions started to recover in the 3rd postoperative week. He was listed as Status 1A at the national Organ Sharing System. The patient's big console precluded his discharge from the hospital. On the 55th postoperative day, he had purulent driveline infection. The antibiogram was studied for Methicillin-sensitive solution . By mid-solution , his las2, 3The prevalence of infection in the LVAD patients has been estimated at between 23% and 58%. Infection is a major mortal complication in patients with mechanical circulatory support. Multiple organ failure is a clinical entity frequently encountered in complicated status after the LVAD implantation. Positive blood cultures in multiple organ failure may be caused or aggravated by various factors.4 reported that a large proportion (41%) of readmissions to the hospital in their study was for complications, most of them related to bleeding or infectious complications.Our patient developed driveline exit-site infection, a subcutaneous infection which needed debridement and curettage. The swab cultures obtained from the driveline exit site were important. Since our patient was listed as Status 1A, infection was crucial to the treatment plan, whereby he would be receiving immunsuppresion therapy after heart transplantation. It was crucial that he be hemodynamically stable and in good status with negative blood cultures. Our main focus was to limit the driveline exit-site infection so that it would be easy to manage the localized infection and prevent it from extending into the sternal cavity. Despite our efforts to control the infection and sepsis, there was always a risk for bleeding-thrombus formation. Since our patient could not survive without the biventricular assist device, we could not explant the pump if his infection was colonized inside the chest and around the pericardial sac. He could not tolerate a second operation like a pump exchange because of his borderline end-organ function. He had high panel-reactive antibodies (PRA) and needed immediate antibody removal with plasmapheresis before heart transplantation. Forest et al.We believe that the appropriate timing of the LVAD implantation is important in patients with advanced heart failure to manage the secondary end-organ dysfunctions and also to increase the survival after heart transplantation. We herein described a young patient with idiopathic cardiomyopathy, advanced end-organ failure, and severe infection who was bridged to heart transplantation after 8 months on the Berlin Heart EXCOR biventricular support.The development of new techniques and strategies in mechanical circulatory support devices for the prevention of infection and bleeding will increase long-term survival and quality of life and also minimize post-implantation complications.


Three dimensional (3D) echocardiography-derived measurements of myocardial deformation and twist have recently advanced as novel clinical tools. However, with the exception of left ventricular ejection fraction and mass quantifications in hypertension and heart failure populations, the prognostic value of such imaging techniques remains largely unexplored.We studied 200 subjects  with known hypertension (n = 51), diastolic heart failure (n = 61), or systolic heart failure (n = 30), recruited from heart failure outpatient clinics. Fifty-eight healthy volunteers were used as a control group. All participants underwent 3D-based myocardial deformation and twist analysis . We further investigated associations between these measures and brain natriuretic peptide levels and clinical outcomes.p<0.001). Global twist measurements were estimated to be 9.49°, 9.77°, 8.32°, and 4.56°, respectively. We observed significant differences regarding 3D-derived longitudinal, radial, and global 3D strains between the different disease categories (p<0.05), even when age, gender, BMI and heart rate were matched. In addition, 3D-derived longitudinal, circumferential, and 3D strains were all highly correlated with brain natriuretic peptide levels (p<0.001). At a mean 567.7 days follow-up (25th–75th IQR: 197–909 days), poorer 3D-derived longitudinal, radial, and global 3D strain measurements remained independently associated with a higher risk of cardiovascular related death or hospitalization due to heart failure, after adjusting for age, gender, and left ventricular ejection fraction .The global 3D strain measurements of the healthy, hypertension, diastolic heart failure, and systolic heart failure groups were 28.03%, 24.43%, 19.70%, and 11.95%, respectively (all 3D-based strain analysis may be a feasible and useful diagnostic tool for discriminating the extent of myocardial dysfunction. Furthermore, it is able to provide a prognostic value beyond traditional echocardiographic parameters in terms of ejection fraction. Heart failure (HF) is a growing epidemic and this problem is largely due to an increasing elderly population New imaging techniques that are able to improve our understanding of cardiac mechanics and assist in the early identification of myocardial dysfunction are rapidly evolving, and it is hoped that they will improve the health care delivery and therapeutic strategies for HF populations 2D speckle tracking imaging (2D-STI) is an angle-independent technique for measuring myocardial deformations  and twist. Previous studies have demonstrated that 2D-STI accurately detects early changes to left ventricle (LV) contractile function before LVEF deterioration, and that it can provide new insights into the understanding of global and regional systolic myocardial mechanics With the advantages of frame-by-frame analysis, and the full volume acquisition of whole LV cavities, real-time 3 dimensional (3D) echocardiography has the potential to circumvent the aforementioned limitations of 2D-STI Previous studies have shown that HTN is a risk factor for myocardial damage and subsequent HF, especially DHF. However, the exact mechanistic alterations that occur during this process remain largely unknown st cohort: 2 months enrollment period from June 1, 2009 to Aug 1, 2009. 2nd cohort: 1 month enrollment period from April 1, 2014 to May 1, 2014. See This was a single center-based retrospective study, comprising consecutive patients (baseline cohorts) that had been referred for transthoracic echocardiography at a tertiary medical center in Taipei, Taiwan , significant valvular heart diseases (moderate degree or above), overt renal failure (serum creatinine level ≥3 mg/dl), malignancy with expected survival <1 year, scheduled cardiac surgery in the near future, and probable difficulties involving follow-up.2) was defined as the ratio of the LV mass to body surface area (BSA) 2D images were obtained using standard parasternal and apical views with frame rates of 80–100 frames/s, with a GE Vivid 7 ultrasound system  equipped with a 2.5–3.5 MHz broadband transducer. M-mode measurements of inter-ventricular septum (IVS), relative wall thickness (RWT), and LV mass were performed. The LV mass index  with full volume electrocardiogram (ECG)-gated 3D datasets . acquireIn the tissue harmonic mode, 3–4 wide-angled acquisitions were made consisting of four wedge-shaped sub-volumes acquired over four consecutive cardiac cycles. These were automatically integrated into a wide-angle (70°×70°) pyramidal dataset with the highest frame rate achievable (20–26 Hz). The data were stored and transferred for off-line analysis. From three consecutive acquisitions, the most optimal image dataset (as determined by an experienced cardiologist) was chosen for subsequent analysis. While analyzing the images, the epicardial and endocardial borders at the end-diastole for the 2- and 4 chamber views, were semi-automatically traced using the Artida software. This method has previously been validated using sonomicrometry 3D echocardiographic parameters, specifically the left ventricular end diastolic volumes (LVEDV), left ventricular end systolic volumes (LVESV), LVEF, global 3D strains, 3D longitudinal strains (LS), 3D radial strains (RS), 3D circumferential strains (CS), and LV twists were then analyzed automatically by the Artida software . The automatic analyses of strain and twist are referred to in The values of 3D-based myocardial strain/deformation components were calculated as percentage changes by the following formula: strain  =  (L1 - L0/L0) ×100 [%], where L1 is the segment length at end-systole, and where L0 represents the segment length at end-diastole. Based on this formula, all 3D-derived myocardial deformation parameters, including LS, RS, and CS, were calculated from different directions or planes of myocardial motion. The global 3D strain was derived by tracking two adjacent points, one on the endocardium and the other on the epicardium, based on a real 3D algorithm from all tracking points distributed on the entire LV myocardium throughout the cardiac cycle, regardless of planes of motion For 3D LV twist calculations, the data was expressed as a degree value representing the short axis apex-to-base gradient of rotation. The measurement of various myocardial deformations and twist using 2D speckle-tracking techniques has been described previously The intra- and inter-observer variability (ICCs) of 3D strain measurements for 18 subjects randomly chosen from this study was 0.89 and 0.85, respectively. The reproducibility of the values obtained in this study was thus shown to be high.Venous blood samples were collected from all participants for biochemical analysis using a Biosite Triage Meter , on the same day of echocardiography. The estimated glomerular filtration rate (eGFR) was estimated by the Modification of Diet in Renal Disease (MDRD) equation Continuous data were reported as the mean ± standard deviation (SD), and were compared using a nonparametric trend test (Wilcoxon rank-sum test) across the ordered disease category groups. Incidence data were expressed as a proportion, and were compared using either the chi-squared or Fisher's exact test, where appropriate. Differences in continuous data between groups was determined via a one-way analysis of variance (ANOVA) followed by the Bonferroni post hoc test for multiple paired comparisons. The statistical power was calculated in a pre-specified manner, with an alpha error of 5% capable of providing significant differences with a statistical power >90% for deformation data  among at least 30 subjects, compared to the control population for each disease category. We further matched age, gender, BMI and heart rate between groups, in order to further disclose the effects of our target myocardial deformations or twist measurements after accounting for the potentially confounding effects of these key clinical variables.Clinical outcomes were defined as HF hospitalization or cardiac death after the study date. The clinical follow-up period was pre-specified, with a follow-up interval of at least 2 years, using the echocardiography examination time as the index date. This was performed to assure that a sufficiently large number of subjects (>25%) would experience a clinical event. Receiver operating characteristic curve (ROC) analysis was used, with an optimal cut-off generated from the largest sensitivity and specificity summation for myocardial deformation strata. Discriminations of area under the ROC  in clinical outcome predictions were performed by C-statistics. Multivariable Cox proportional hazard regression models were used to identify the independent role of myocardial deformation in predicting clinical outcomes, with hazard ratio (HR) and 95% CI reported. The likelihood ratio test was used for comparisons of the incremental values for different echo-derived parameter combination models. The original value of 3D LS and 3D CS acquired from 3D echocardiography, were presented in the same direction as 2D-derived LS and CS values (as negative). In order to present our data uniformly among all 3D-derived strain components and clinical correlates or outcomes, we calculated and expressed the “absolute values” of 3D LS and 3D CS (as positive) during our data analysis.p value of <0.05 was considered statistically significant. Statistical analyses were performed with STATA software for Windows, version 9.0  A two-tailed Of the 214 subjects initially enrolled, a total of 200 had complete baseline information and sufficient quality 3D images rendered for myocardial strain tracking, with baseline information according to different disease categories  .p<0.05). Compared to the other groups, subjects with DHF were older and had a higher BMI (both p<0.05). Additionally, patients with HF (both DHF and SHF) had significantly higher BNP levels than the other two groups (p<0.001), with the SHF group having the highest BNP (log 5.4±1.61). In addition, DM, hyperlipidemia, and coronary artery disease (CAD) were more prevalent in patients in the three diseased clinical categories.Subjects in the HTN, DHF, and SHF groups tended to be older, with higher SBP, and with poorer renal function  as compared to the control group , 3D CS , 3D RS , and 3D twist .Measurement comparisons of LV strain and torsion between the 2D and 3D echo methods are shown in p<0.001). The SHF group also had significantly lower LVEF (3D) , IVRT , DT , and mitral annulus velocity E′  values compared to the other disease categories, whereas subjects in the HTN group had the lowest mitral E/A ratio (0.97±0.38). Compared to the control group, the HTN and DHF groups both had a higher ventricular septal wall and relative wall thickness, as well as a lower mitral annulus E′ velocity . In addition, the DHF group demonstrated a higher LV mass (with and without index), as well as a larger myocardial 3D volume and PCWP (E/E′), when compared to the control group . Comparisons between LV global 3D strain and strains from various directions, as well as twist across the four categories are shown in p<0.001, respectively). However, the differences were less obvious in the CS  and twist  between the control and DHF groups . Finally, the differences between the 3D-based myocardial deformation and cardiac twist measurements between the four groups did not change significantly after matching for age, gender, BMI and heart rate variables . Additionally, subjects with a history of CAD were more likely to have reduced deformation parameters in all directions, as well as decreased cardiac twist . The association between all 3D-derived strain components and serum BNP levels was highly correlated throughout the entire cohort . A clinical history of HTN and a higher heart rate were related to a reduced LS and global 3D strain (both p<0.05). Increasing LV wall thickness was also related to reduced myocardial strain and cardiac twist (both p<0.05). A reduction in mitral annular diastolic relaxation velocity (E′) and an elevated LV filling pressure were both associated with reduced strain from all directions .Using linear regression analysis, we examined the associations between global 3D and other strain components, with clinical variables  and convst cohort entered the follow-up period with sufficient observation intervals . The predictions of cardiac death or HF hospitalization using different methodologies of 3D echocardiography were determined (th–75th IQR: 197–909 days). In the unadjusted model, all 3D-based measures , conferred a significantly increased HR for clinical events . After an adjustment of clinical variables such as age and sex with 3D-defined LVEF, the HR remained independently as 1.16 (95% CI: 1.04–1.29) for 3D LS and 1.07 (95% CI: 1.10–1.15) for 3D RS. Additionally, HRs were estimated to be 1.22 (95% CI: 1.13–1.32) for 3D LS, 1.10 (95% CI: 1.02–1.17) for 3D RS, 1.13 (95% CI: 1.07–1.20) for 3D CS, 1.16 (95% CI: 1.08–1.23) for global 3D strain, and 1.15 (95% CI: 1.02–1.29) for 3D twist when LV mass (M-mode) was adjusted together with clinical age and sex . Similar results were observed if the 3D-based myocardial volume as well as age and sex were adjusted .For all participants with registered final follow-up data, only the 1termined . A totalp for delta AUROC <0.05).The cut-off values of each parameter for predicting clinical outcomes were analyzed by using the ROC method  on clinical outcome predictions when superimposed on 3D LVEF, 2D TDI E′, and 2D LA volumes, respectively  can aid in characterizing the extent of myocardial dysfunction in subjects with HTN or HF (both systolic and diastolic). In line with previous reports, we observed that graded longitudinal functional decline may occur in subjects with HTN or DHF, which is in part compensated by relatively well preserved short-axis function or twist Although the numbers in this study were small, it appeared that the subjects in the HTN group were at a stage of more impaired diastolic relaxation, denoted by an inverted E/A ratio. Notably, HF with preserved LVEF, namely DHF, has comprised nearly half of all patients with HF in recent years Compared to 2D-derived myocardial deformation, 3D-based strain measurement is a novel and newly developed technique that can help to assess cardiac mechanics more rapidly and in a more comprehensively detailed and reproducible manner In previous studies, LVEF obtained by transthoracic 2D echocardiography has emerged as the most important clinical variable in determining the extent of systolic dysfunction for guiding therapeutic decisions There are several limitations to this cohort study. Our data and conclusions may need to be interpreted with caution, in part because of the study's retrospective nature and the relatively small numbers used in both the disease and control groups. Important risk factors , which were not considered due to the small number of clinical events, may also limit the study's validity. Furthermore, renal function, and other medical histories of the DHF group did not match the other study groups, even after matching for age, gender, BMI and heart rate. This may potentially make the comparisons between the study and control groups invalid. Therefore, we suggest that additional larger, more rigorous, and more comprehensive prospective studies be conducted in the future.This clinical study aimed to examine the relationship between LV function and mechanics in subjects with a variety of clinical conditions, by using novel 3D-based myocardial tracking techniques. We proved this technique to be clinically feasible and that it can aid in characterizing the extent of myocardial dysfunction in various pathophysiological states. We also successfully demonstrated that 3D strain based measures were superior to LVEF in predicting clinical outcomes, including HF events and life expectancy.S1 FigA flow chart of the current study, including the initial total number of participants (n = 214). Fourteen were excluded due to poor image quality, unavailable baseline information (n = 1), or two loss in the follow-up. The final total baseline study cohort number was 200. During a mean 567.7 days of follow-up period, there were 131 subjects who had follow-up data available.(TIF)Click here for additional data file.S2 FigAn illustration of automatic strain analysis. Strain curves for the apical four-chamber view shows A: longitudinal strain, B: radial strain, C: circumferential strain, and D: 3D strain, respectively, in the healthy subjects.(JPG)Click here for additional data file.S3 FigAn illustration of automatic strain analysis. Strain curves for the apical four-chamber view shows A: longitudinal strain, B: radial strain, C: circumferential strain, and D: 3D strain, respectively, in the heart failure subjects.(JPG)Click here for additional data file.S4 FigAutomatic twist analysis of the left ventricle. Twist curves of the apical four-chamber view shows A: healthy subjects, and B: heart failure subjects.(JPG)Click here for additional data file.S1 FileS1 Table. Baseline demographic characteristics of the study subjects after matching. *p<0.05 vs. Control group; †p<0.05 vs. HTN group; ‡p<0.05 vs. DHF group; and §p<0.05 vs. SHF group. Abbreviations as in S2 Table. Baseline key echocardiography parameters or diastolic indices after matching. *p<0.05 vs. Control group; †p<0.05 vs. HTN group; ‡p<0.05 vs. DHF group; and §p<0.05 vs. SHF group. Abbreviations as in S3 Table. Comparisons of 3D-based deformations and cardiac twist after matching. *p<0.05 vs. control group; †p<0.05 vs. HTN group; ‡p<0.05 vs. DHF group; and §p<0.05 vs. SHF group.Contains the following files: (DOCX)Click here for additional data file.


Right ventricular (RV) function holds important prognostic value in both right- and left-sided acquired and congenital heart diseases. However, assessment of RV function remains challenging due to its complex chamber geometry and physiology. 4D flow CMR permits assessment of multidimensional intraventricular flow. We hypothesized that 4D flow specific markers of RV function can detect subtle impairment of RV function in primary left ventricular (LV) disease.Eighteen patients with mild ischemic heart disease and eleven healthy controls were enrolled. 4D flow CMR and standard morphological images were acquired on a 3T-scanner (Philips Ingenia). The patients were stratified into two groups (n=9 each) based on LV end-diastolic volume index (EDVI) from CMR: lower LVEDVI and higher LVEDVI, respectively. The RV volume was segmented from morphological images at end-diastole (ED) and end-systole (ES) and matched to the velocity data. Pathlines were emitted from the ED volume and traced forwards and backwards in time, to the time of ES, encompassing the cardiac cycle. The blood volume was separated into functional flow components Figure . The DirResults are displayed in Table These findings suggest that in primary LV disease, mild impairment of RV function can be detected by 4D flow CMR, but not by the majority of conventional CMR and echocardiographic indices. These flow-specific alterations propose novel pathophysiological aspects of interventricular function that could add to the assessment of integrated cardiac function in the context of medical, pacing and surgical strategies.The Swedish Heart-Lung Foundation.


Mid-wall fibrosis (MWF) is a hallmark of non-ischemic cardiomyopathy (NICM) that confers increased risk for sudden cardiac death and mortality. The relationship between MWF and left ventricular (LV) remodeling is unknown.The population comprised patients with advanced systolic dysfunction (LVEF ≤ 40%) undergoing CMR . Ischemic vs. NICM etiology was classified in accordance with established convention based on obstructive CAD on invasive angiography. Delayed enhancement CMR (IR-GRE acquired 10-30 minutes post gadolinium [0.2 mmol/kg]) was used to identify MWF, defined as hyperenhancement confined to the mid-myocardial or epicardial aspect of the interventricular septum. LV mass and chamber volume were quantified by planimetry of contiguous SSFP cine-CMR short axis slices, with ejection fraction (EF) calculated as the proportional difference between end-diastolic (EDV) and end-systolic (ESV) volumes.2 = 91.2; p < 0.001) model for MWF was higher than that of isolated clinical  and imaging  models.523 patients  were studied: MWF was present in 16%, and was 6-fold more common in patients with angiographically classified NICM . Regarding LV remodeling, MWF was associated with higher EDV  and LV mass  and lower LVEF . MWF was nearly 3-fold more common among patients in the highest tertile of EDV vs. the remainder of the population . Multivariate regression analysis was performed to further assess markers for MWF: Restricted to imaging indices, results .


Patients with non-ischemic heart failure etiology and left bundle branch block (LBBB) show better response to cardiac resynchronization therapy (CRT). While these patients have the most pronounced left ventricular (LV) dyssynchrony, LV dyssynchrony assessment often fails to predict outcome. We hypothesized that patients with favorable outcome from CRT can be identified by a characteristic strain distribution pattern.n = 10; LVESV reduction ≥15 %). Longitudinal strain (εlong) data were obtained by speckle tracking echocardiography before and after (9 ± 5 months) CRT implantation and standardized segmental εlong-time curves were obtained by averaging individual patients.From 313 patients who underwent CRT between 2003 and 2006, we identified 10 patients who were CRT non-responders (no LV end-systolic volume [LVESV] reduction) with non-ischemic cardiomyopathy and LBBB and compared with randomly selected CRT responders (p = 0.002), while in non-responders, EF was unchanged . Global εlong was significantly lower in non-responders at pre CRT (p = 0.02) and only improved in responders (p = 0.04) after CRT. Pre CRT septal εlong -time curves in both groups showed early septal contraction with mid-systolic decrease, while lateral εlong showed early stretch followed by vigorous mid to late contraction. Restoration of contraction synchrony was observed in both groups, though non-responder remained low amplitude of εlong.In responders, ejection fraction (EF) increased from 25 ± 9 to 40 ± 11 % (long pattern with responders after CRT implantation, while amplitude of εlong remained unchanged. Lower εlong in the non-responders may account for their poor response to CRT.CRT non-responders with LBBB and non-ischemic etiology showed a similar improvement of ε Cardiac resynchronization therapy (CRT) improves survival by stopping or reversing adverse remodeling that occurs in systolic heart failure –3. The mWhile several clinical parameters have been well established as predictors of CRT response , 3, 6, fThe study population was selected from 313 consecutive heart failure patients who underwent implantation of a biventricular device at the Cleveland Clinic between January 2003 and June 2006, who also had long-term echocardiographic follow-up  at follow-up) with the following clinical characteristics: non-ischemic cardiomyopathy, LBBB, and LV lead placed over the base/mid posterior or lateral LV wall. We compared this group with a group of ten patients with the same characteristics except for being CRT responders (reduction of LVESV at follow-up ≥15 %) who were randomly selected from the same study population. The patient data were de-identified and that the study was approved by the Cleveland Clinic Institutional Review Board.long) curves derived from a single cardiac cycle were exported for analysis, with resulting 18 εlong curves corresponding to the basal-mid-apical septum, anteroseptum, inferior, posterior, lateral and anterior segments obtained in each patient. To correct for RR interval variation, εlong curves were normalized using the two reference time points of end-diastole and end-systole, so that time was expressed as a percentage of systole (% systole) [Two-dimensional speckle tracking  was performed using the images acquired in the apical 4 chamber, 2 chamber and long axis views. The peak of the R wave on the ECG was used as a reference time point for end-diastole, and aortic valve closure was used as a time point for end-systole. Segmental longitudinal strain (εsystole) . Care walong profiles in both patient groups pre and post CRT, individual εlong curves were averaged to obtain a characteristic average εlong profile [long curves of the basal anterolateral segment (A), and corresponding group average εlong curve (B) obtained in CRT responders before pacing. Finally, global εlong was calculated by averaging segmental values.To better characterize segmental ε profile , 9. FiguU test as appropriate. To assess opposing wall mechanics before and after CRT, we entered εlong measurements from basal and mid LV levels of the opposing walls  obtained at early systole (50 % of systole duration), end-systole (100 % of systole duration) and post-systole (125 % of systole duration) into mixed model analysis, using an unstructured covariance model. The model was constructed with “time” (% systole) as covariate, and “wall”  and “group” (responders vs. non-responders) as factors. Interaction between time and wall, which quantitates between-wall difference in pattern of εlong development, was taken to represent loss of coordinated contraction (dyssynchrony). The Akaike criterion was used to determine the optimal model. P values <0.05 were considered as statistically significant. Statistical analyses were performed using JMP Pro 10.0.2 .Continuous variables with normal distribution were expressed as mean ± SD, and categorical variables were expressed as count and percentage. Between and within-group differences were assessed by Wilcoxon signed-rank test and Mann-Whitney n = 12) and posterolateral (n = 7) cardiac veins. There was no difference between these two groups.Of the 313 consecutive patients who underwent CRT and follow-up, 155 (50 %) had reverse remodeling and 89 (28 %) patients had no response to CRT. Of those 89 patients, 10 (11 %) patients met the inclusion criteria. Among patients who responded to CRT, 38 patients met the inclusion criteria and 10 patients were randomly selected as the comparison group. The baseline clinical, electrocardiographic, and echocardiographic characteristics were similar between responders and non-responders (Table p = 0.01), LVESV (p = 0.002), and EF (p = 0.002), while non-responders showed significant enlargement of LVEDV (p = 0.004) and LVESV (p = 0.01). Although there was no difference in LV volumes or ejection fractions between the two groups before CRT, LVEDV (p = 0.008) and LVESV (p = 0.002) were significantly smaller, and EF (p = 0.002) was higher in responders after CRT implantation.Baseline left ventricular volumes and ejection fraction were not different between responders and non-responders Table . At folllong values in responders and non-responders at mid-systole (50 % systole), end-systole (100 % systole) and early post-systole (125 % systole). Before CRT, global εlong at end-systole (p = 0.02) and early post-systole (p = 0.03) were lower in the non-responder group. At a follow up, in addition to end-systole and early post-systole εlong, non-responders showed lower global mid-systole εlong (p = 0.03). In responders, global end-systolic (p = 0.04) and early post-systolic εlong (p = 0.03) demonstrated improvement after CRT implantation, whereas there were no significant improvement in non-responders.Table long-time curves of 18 segments in responder and non-responder. Each panel showed pre- and post-CRT septal and lateral wall εlong-time curves of basal, mid, and apical segment for responders and non-responders. Pre- CRT, the basal and mid septal εlong-time curves demonstrated a pattern of early septal contraction with mid-systolic decrease, while basal and mid lateral εlong-time curves demonstrated an early stretch followed by vigorous mid to late contraction. Post-CRT, restoration of contraction synchrony was noted in both the septal and lateral segments. This pattern pre- and post-CRT was to a lesser extent observed in the posterior and anteroseptal walls respectively .To quantify these observations, we compared εlong was lower in the lateral than in the septal wall (p = 0.001). Septal and lateral walls were also different in the pattern of εlong increase . After CRT, lateral wall εlong was still higher (p = 0.007), but difference in the pattern of εlong increase disappeared (p = 0.80). Responders showed higher overall εlong (p = 0.02), and more marked εlong increase over time (p = 0.03).Prior to CRT, εlong increase (p = 0.01), but similar average εlong (p = 0.20) . After 12 months of CRT, difference in the pattern of εlong increase in opposing walls disappeared (p = 0.70). Responders showed a trend towards having higher overall εlong (p = 0.08).Posterior and anteroseptal walls prior to CRT showed different patterns of ε20) Fig. . Intereslong increase (p = NS) . After 12 months of CRT, responders showed higher overall εlong (p = 0.02), again with no difference between εlong of opposing walls (p = NS).Inferior and anterior walls before CRT had similar patterns of εNS) Fig. . Respondlong was significantly associated with CRT response. The area under the receiver operating characteristic curve showed average εlong at end systole -4.0 % as optimal cutoff point . This cutoff point predicted CRT response with 78 % specificity and 80 % sensitivity in this population. Other echocardiographic parameters and baseline characteristics did not predict response.In the logistic regression model, the pre CRT average εIn this paper, CRT non-responders despite having favorable predictors of good response to CRT  have lower global end systolic longitudinal strain but a similar pattern of longitudinal strain contraction heterogeneity pre-CRT as responders. This indicates that the presence of, and subsequent improvement of, dyssynchrony is not sufficient to result in reverse remodeling during CRT. Their markedly lower longitudinal strain suggested myocardial dysfunction burden might be the predictor of reverse remodeling in patients with non-ischemic cardiomyopathy.Animal models have demonstrated that right ventricular pacing (an LBBB surrogate) induces a characteristic pattern of blunted early septal and forceful delayed lateral wall contraction preceded by its early stretch , 5, 10. The improvement of LV contraction heterogeneity underlies some of the benefits of CRT. Unfortunately, prospective multi-institutional trials failed to confirm the predictive value of the most frequently used dyssynchrony indices , 19. EveThe MADIT-CRT cohort also supported that decreased average longitudinal strain predicts less beneficial effects of CRT, especially in the setting of LBBB , 27. SevThis is a small, retrospective, observational study. Only longitudinal strains were assessed, although various previous studies have used circumferential or radial strains , 16. HowOur study defines the characteristic segmental pattern of LV contraction in patients with non-ischemic cardiomyopathy and LBBB before and after CRT. CRT non-responders with non-ischemic cardiomyopathy and LBBB demonstrated a qualitatively similar segmental contraction pattern but have dramatically decreased longitudinal strain. These findings may help in predicting the outcome of CRT in these patients.


The contrast agents used in ultrasound are approved for several clinical situations. New echocardiographic techniques, such as harmonic imaging and power pulse inversion imaging, can improve the visualization of microbubbles. In this article we discuss the early development of contrast echocardiography, new technologies that help improve image acquisition and its practical role in the assessment of myocardial infarction. Technological advances and the use of contrast agents more stable in the circulation have positioned contrast echocardiography as a safe and effective technique for the assessment of myocardial perfusion. The clinical applications of contrast echocardiography include the assessment of patients with suspected or known coronary artery disease; determination of the area at risk and efficacy of reperfusion therapies in patients with acute myocardial infarction; and assessment of myocardial viability after infarction (no-reflow phenomenon).Contrast echocardiography is a technique that uses microbubble contrast agents administered via peripheral veins to improve the echocardiographic signal. Since these microbubbles were large, they would not cross the pulmonary barrier, so their use was limited to the opacification of the right cardiac chambers.The use of agitated saline solution as an echocardiographic contrast agent to enhance blood within the heart was first described by Gramiak and Shah in 1968, based on the creation of a gas-blood interface. Because these microbubbles had a small diameter and were room-air filled, they persisted only for a short time in the systemic circulation, and dissolved in blood easily. Additionally, they underwent quick destruction when exposed to ultrasonic energy, which made it difficult for them to be applied in the study of the myocardial flow.The sonication process developed by Feinstein et al. enabled the reduction of the microbubble size, thus permitting their passage through the pulmonary capillary circulation, and consequent opacification of the left cardiac chambers.The use of high molecular weight less diffusible gases resulted in the production of more stable contrast agents capable of remaining in the systemic circulation for a longer time.The first-generation contrast agents are composed of room-air-filled microbubbles. The composition of second-generation contrast agents, in turn, include high molecular weight gases; these agents are enclosed by a protein, lipid or chemical-polymer capsule, and show lower diffusivity and more stability, which permit their passage through the pulmonary capillary barrier. Thus, they can reach the left heart chambers and, consequently, the coronary microcirculation. The development of new ultrasound systems capable of identifying second-harmonic signals permitted the formation of the “second-harmonic images”, with preferential detection of signals originating from the microbubbles. This imaging modality represented a great advance in the improvement of quality of two-dimensional images, because of the higher resolution of the image and definition of the endocardial borders provided by ventriculography obtained by the presence of microbubbles in the left ventricular (LV) chamber, with a consequent more adequate analysis of both the regional and global motion.When hit by an ultrasound beam, the microbubbles vibrate and reflect waves with multiple sound frequencies from the fundamental frequency emitted by the ultrasound scanner, which are known as harmonicsHowever, the use of high-energy ultrasound , present during the performance of fundamental-image or even second-harmonic studies, cause the microbubbles to collapse. The fast destruction of microbubbles makes the assessment of the myocardial perfusion impossible when only second-harmonic imaging is used. A means to avoid this problem is to emit intermittent ultrasound pulses every two, three, four, or even ten heart beats. Thus, after a first pulse of high-energy ultrasound, there is complete microbubble destruction in a given ultrasonic field. Since the next ultrasound pulse is emitted only seconds after the first one, there is time for the microbubbles to refill all the microvascular bed, thus making the myocardial perfusion study possible, with acquisition of static images, without motion in real time ..The study of myocardial perfusion by echocardiography implies the peripheral intravenous administration of microbubble contrast agents which, because of behaving similarly to the red blood cells, are excellent markers of myocardial flow, thus determining the integrity of the coronary microcirculationRecently, another imaging modality known as real-time myocardial perfusion echocardiography (RTMPE) was developed. It permits the concomitant analysis of myocardial reperfusion and segmental LV contraction. However, the signal originating in the microbubbles is relatively weak using this technique. With the purpose of overcoming this limitation, the alternating-amplitude pulse technique is used; this consists of the emission of two energy pulses in which a pulse is half the amplitude of the other. At reception, the pulse with half the amplitude is multiplied by two. These signals are subtracted, so that structures responding in a linear fashion (tissues) will show a reduction or absence of signal in the end, whereas structures responding in a non-linear fashion (microbubbles), will show a signal different from zero, thus being detected ..Since practically no microbubble destruction occurs, the myocardium becomes saturated with them, and their intensity remains constant. Then, there is another key component – the emission of two to five high ultrasound energy pulses, flash , for myo,13.Myocardial opacification has proven to be a promising path for the diagnosis and prognosis of patients with acute myocardial infarction (AMI), for having the potential of supplying qualitative and quantitative information on the regional and global LV microvascular flowμm in diameter. In this complex system, the total coronary flow corresponds to an average of 4% to 5% of the cardiac output and, in baseline conditions, 8% of the LV mass is comprised of the blood present in the microcirculation, 90% of which is within the capillaries, then known as myocardial blood volume. The coronary blood flow velocity is directly related to the diameter of the vessels; it is approximately 40cm/s in epicardial arteries and 1mm/s or less in the capillaries of humans. The microcirculation is not only a passive channel through which blood is transported in the myocardium, but rather an active site of blood flow control with a complex regulation which depends on metabolic and myogenic mechanisms. For the capillary exchange to be preserved, several physiological mechanisms keep the capillary hydrostatic pressure constant in the myocardium at approximately 30mmHg, with pre and post-capillary pressures of approximately 45 and 15mmHg, respectively. The coronary arterioles act as resistance vessels. They have smooth muscle and show immediate myogenic response, and that is why the arteriolar resistance can change from second to second in order to keep the pre-capillary pressure constant. On the other hand, the coronary venules present a poor myogenic response and control the local resistance by changing the rheological properties of the blood. Capillaries are very small and offer high resistance. However, since they are arranged in parallel, the total capillary resistance decreases with the increase in the number of capillaries. At rest, approximately 60% of the total myocardial vascular resistance is offered by the arterioles, 25% by the capillaries, and 15% by the venules. By means of retrograde stimuli, usually measured by the increase in oxygen consumption, higher or lower capillary recruitment can occur. In baseline conditions, approximately half of them is not working.The vascular compartment in the myocardium comprises the great arteries, arterioles, the capillary network and smaller intramyocardial veins. The coronary microcirculation is defined by being composed of vessels smaller than 200Recently, it has been demonstrated that ultrasound-induced microbublle destruction can be used for the measurement of the myocardial blood flow during continuous infusion of a contrast agent. The relative agent concentration in different myocardial beds represents the capillary density or the sum of its crosssectional area. Microbubbles may be destroyed by some high-energy ultrasound pulses and, from then on, their rate of reappearance in the myocardium may be measured, and represents the mean microbubble velocity in the microcirculation. This is possible because, after being destroyed, the time available for another microbubble inflow to cover any distance within the ultrasound beam is determined by the increase in the acoustic intensity (AI) in a given ultrasound pulse interval . On the other hand, the microbubble concentration in the microcirculation is directly proportional to AI, and reflects the microvascular blood volume. Thus, for any pulse interval, the AI within the beam will be proportional to the distance covered by the microbubbles within the beam. Since the microbubble velocity is constant in the microcirculation, the AI will be greater as the time of exposure to lowenergy ultrasound increases, up to the moment when capillary saturation within the ultrasound beam is reached. Therefore, the AI, at this moment, will remain constant, thus reflecting the relative concentration of microbubbles in the tissues..When the microbubbles are continuously administered intravenously, at a constant infusion rate and concentration, a steady state is achieved, in which the microbubble concentration in the blood is equal to that in the myocardium. Thus, considering that the microbubble concentration within the myocardium is proportional to the blood volume fraction, and knowing the blood flow velocity, it is possible to estimate the myocardial blood flowThere are three models of myocardial blood flow quantification using contrast echocardiography. The first is the visual analysis, which is semiquantitative, subjective, limited to the observer's experience, and based on the determination of perfusion scores that range from normal perfusion to absent perfusion. This commonly assesses only the microvascular blood volume component and, due to a limitation of the human's eye perception, valuable information on the blood flow velocity is missed. The second is myocardial blood volume quantification (represented by the letter A), and of the myocardial blood flow velocity (represented by the Greek letter ß) in regions of interest (ROI) in the myocardium, using a specific computer program. The third model consists of parametric imaging, a novel method of automated quantification in which the myocardial blood flow is codified in colors all over the myocardium, according to the degree of perfusion. Color grades are linearly applied based on mean values, with cut-off points fixed in the mean values (green), values between two thirds and one third of the mean values (yellow), and values below one third of the mean value (red), corresponding to normal, decreased, and significantly decreased perfusion, respectively.μm. In this study, 78% of patients with adequate collateral circulation for the infarct bed on contrast echocardiography showed improvement in the regional systolic function 30 days after flow was reestablished. Of these, only 17 patients showed collateral circulation on angiography. These data indicate that, in addition to the duration of coronary occlusion, the extent of residual myocardial perfusion is also determinant of the infarct size.Sabia et al. studied 43 patients who had had an inferior myocardial infarction two days to five weeks earlier and occluded right coronary artery using direct contrast injection in the left coronary artery. They demonstrated that, after the intracoronary injection, there was opacification of the whole myocardium in 32 patients, thus suggesting collateral circulation for the infarct area. On the other hand, coronary angiography did not show abundant collateral circulation, thus demonstrating that contrast echocardiography is more accurate in the assessment of collateral vessels, since angiography only defines vessels greater than 100. The moment the coronary was opened, reflow was found only in the areas with an anatomically preserved microvasculature, whereas no reflow was observed in the areas with a damaged microvasculature. This failure to achieve reperfusion following prolonged ischemia, first postulated by Krug et al. and later demonstrated by Kloner et al., is called the no-reflow phenomenon,22.Acute coronary occlusion leads to cell necrosis and consequent permanent functional myocardial damage. Kloner et al. assessed the event time in an experimental model and demonstrated that after 40 minutes of ischemia for coronary occlusion, a variable amount of myocytes was necrotic, whereas the microvascular network was still intact. Ninety minutes or longer after coronary occlusion, a large percentage of myocardial cells was damaged, and the microvasculature showed loss of its anatomical integrity. In a similar experimental model, Ambrosio et al. found a progressive loss in the intramyocardial reflow, with a late no-reflow area (3 to 5 hours after reperfusion) almost three times larger than the no-reflow area after early reperfusion (2 minutes after reperfusion).In an experimental model (90 minutes of coronary occlusion followed by reperfusion), Jeremy et al. showed that, in the first 4 hours after the opening of the coronary artery, the region without microvascular perfusion became progressively larger in the area related to the infarct, and this occurred because of microvascular occlusion by neutrophils in the postischemic myocardium.Using microbubble contrast echocardiography via intracoronary injection, Ito et al. studied the no-reflow phenomenon in patients with anterior AMI who had an early recanalization (within 6 hours from the onset of chest pain) and demonstrated that the angiographic success of reflow (TIMI grade 3 flow) did not necessarily indicate an adequate myocardial perfusion. Thus, the no-reflow phenomenon is an expression of microvascular damage and is associated with more extensive myocardial necrosis and worse regional and global contractile function.In another study of patients with anterior-wall AMI undergoing primary angioplasty, Ito et al. used intracoronary injection of microbubble contrast and demonstrated that, if more than 25% of the area at risk remained with a perfusion defect after recanalization, incomplete reperfusion would occur, thus determining what they defined as no-reflow. In the 30-day follow-up, the LV ejection fraction improved only in the group with TIMI grade 3 flow and absence of no-reflow.Caldas et al. used echocardiography with intermittent imaging and contrast administered via a peripheral vein to study 31 patients within the first 48 hours of a primary anterior-wall AMI successfully treated with fibrinolytic drugs or percutaneous coronary intervention. The LV myocardial perfusion score was demonstrated to be an independent predictor of left ventricular remodeling and was proportional to the segmental contractility index score in the 6-month follow-up. The presence of the no-reflow phenomenon had a greater impact on the left ventricular remodeling than in the myocardial segments with reduced perfusion (low-reflow). After 6 months, patients with more than two myocardial segments without opacification after contrast showed functional recovery or contractile reserve in only 28% of the myocardial segments supplied by the anterior descending coronary artery. On the other hand, patients with two or less segments without opacification showed, in 6 months, recovery of the contractile function at rest or contractile reserve in 70% of the segments supplied by the anterior descending coronary artery.Sbano et al. studied 50 patients with AMI treated with fibrinolytic therapy and demonstrated that the group that progressed with recovery of the left ventricular function within 6 months showed perfusion in 65.8% of the infarct-related segments on contrast echocardiography with intermittent imaging performed in the first week after the event. The group presenting perfusion in only 25.5% of the infarct-related segments, in turn, progressed with no improvement of the left ventricular function. All myocardial segments without perfusion on contrast echocardiography showed no recovery of the contractile function within a period of 6 months.Trindade et al. observed an excellent correlation between real-time myocardial perfusion echocardiography, specially the parametric imaging, and magnetic resonance imaging, as regards the measurements of the infarct size and its percentage, as well as in the determination of its transmural extent in 30 patients hospitalized for primary AMI treated with fibrinolytic drugs or primary percutaneous intervention within up to 12 hours after the event.In summary, contrast echocardiography has a good safety and efficacy in the assessment of coronary artery disease


Non-invasive assessment of PA pressure and pulmonary vascular resistance (PVR) is vital in children with PAH. Unfortunately TR jet velocity is difficult to measure in using CMR. Therefore, we hypothesized that septal curvature (SC) assessed using CMR could be used to estimate PA pressure and track acute changes in pulmonary hemodynamics. In this study SC was compared to simultaneously acquired PA pressure and PVR in children undergoing combined cardiac catheterization and CMRThe study included 50 children (median age of 6.6 years range 0.5-16.5 years) with either idiopathic PAH (n = 29) or PAH associated with repaired congenital heart disease (n = 17) or lung disease (n = 4). The combined CMR/catheterization was perfomed under general anesthetic and PVR was calculated using phase contrast flow and simultaneously acquired invasive PAP and wedge pressure at baseline and during vasodilation (100% 02 and 20ppm NO). SC was measured in short axis cine images at papillary muscle level using real time k-t SENSE and an in-house plugin for the OsiriX platform. A control population of 15 healthy pediatric volunteers (range 10.1-14.1 years) also underwent CMR (awake) and assessment of septal curvature (SC)There was a significant difference (p < 0.05) between mean SC in the patient group  compared to the control group . Importantly, there was no overlap between SC in normal controls and SC in patients. There was a strong correlation between mPAP and SC at baseline and during vasodilator testing  [Figure The main findings were: i) There was a significant difference in SC parameters between normal controls and children with PH; ii) SC derived metrics strongly correlated with mPAP and PVR in patients; and iii) SC derived metrics were able to track acute changes in pulmonary hemodynamics during vasodilator testing. We believe that these results show that SC metrics could be used as a non-invasive adjunct to catheter assessment in pediatric PH. Importantly, the fact the SC metrics track changes in pulmonary hemodynamics mean that they could be use to track disease progression or response to therapy. Furthermore, they could also be used to identify patients with vasoresponder status.British Heart Foundation and UK National Institute of Health Research.


Transcatheter aortic valve implantation (TAVI) has become a common procedure for high-risk patients with severe aortic stenosis. Aortic regurgitation (AR) is commonly seen after TAVI, but little is known about how it evolves over time. Similarly, the impact of TAVI on left ventricular (LV) function, LV volumes and mass is not well defined.Paravalvular aortic regurgitation (AR) is frequent after TAVI. Yet, little data is available about temporal changes of AR and the impact of TAVI on left ventricular (LV) function and dimensions.We used cardiac MRI to evaluate LV function, volumes and mass, the occurrence and degree of AR in the early and medium-term follow-up after TAVI.In 81 patients who underwent transfemoral TAVI using the Medtronic Corevalve prothesis or the Edwards Sapien valve we performed baseline cardiac MRI at a median of 11 days after TAVI and follow-up MRI 6 months later.LV volumes and function were assessed using standard cine MRI sequences. Additionally, phase contrast imaging was conducted to measure aortic regurgitation.A calculated RF of 1%-15% was graded I (mild), 16%-30% was graded II (moderate), 31%-50% was graded III (moderate to severe) and > 50% was graded IV (severe), a RF <1% was classified as no AR.The median age of the evaluated patients was 81 years (range 61 - 90y) and 60% were women. At baseline MRI, the median LV ejection fraction was 58.0% (range 22.1-71.7%), which improved significantly at follow-up to 63.4% .In addition, a significant reduction of LV end-diastolic volume  and of LV mass  was observed.Baseline MRI identified no AR in 15 patients, grade I AR in 55, grade II in 9 and grade III AR in 2 patients. The median aortic RF was 4.2% (range 0.1 to 39.0%) at baseline and remained stable with 5.0%  at follow-up.The changes in LV function, volume and mass observed in the oberall cohort were not present in the subgroup of patients with relevant AR  at baseline MRI: the mean ejection fraction only showed a trend to improvement  whereas the mean LV end-diastolic volume  and LV mass  were almost identical at baseline and follow-up.Using cardiac MRI in TAVI patients, a significant improvement of left ventricular function, volume and mass can be documented after TAVI. Aortic regurgitation which is mostly mild is commonly seen in patients treated with TAVI. The aortic regurgitant fraction remained stable over time. Yet, positive left ventricular remodelling could only be observed in patients with no or mild AR after TAVI whereas no changes occured in the subgroup of patients with relevant AR.None.


The tractographic propagation angle (PA) is a topographic measure of fiber architecture in the myocardium. We have previously shown in infarcted mice that a PA > 4° can be used to differentiate normal and infarcted myocardium . Here, ® 3D electroanatomic mapping system. The hearts were then perfusion-fixed and excised. Cardiac diffusion tensor MR imaging (DTI) was performed on a clinical 3T scanner, as previously described , where a = 0.47, b = 7.14, c = 1.69, and d = 1.09 with root mean square error = 1.99.Little variation in PA was observed between normal ovine and human myocardium Figure . Marked p Figure . PA in n° Figure  but signs Figure . Bipolarr Figure . The relin vivo has become possible, which could allow PA to serve as a valuable tool in the assessment and management of patients at risk of sudden cardiac death.A narrow range of PA exists in normal hearts, and PA can be used to delineate regions of normal myocardium, heterogeneous scar, and dense scar. Regions of myocardium with very high PA values (> 10°) likely lack the structural coherence to support electrical conduction. PA values between 4-10°, however, correlate well with the bipolar voltage values seen in heterogeneous and arrhythmogenic scars. Recently, tractography of the entire human heart R01 HL093038 (D.E.S.), R01HL112831 (D.E.S.), P41RR14075 (Martinos Center).


Sympathetic stress is a trigger of TCM and is probably underdiagnosed and not uncommon in ICU patients . We haveal model .treatment, could attenuate the degree of LV dysfunction and reduce mortality in a TCM animal model.In the present study, we examined whether isoflurane, when used for TCM was induced in seventy-five propofol sedated animals by intraperitonial injection of isoprenaline (50 mg/kg). Within 90 minutes after injection, the animals develop tako-tsubo-like heart failure with apical dyskinesia/akinesia and reduced cardiac output . The aniEarly institution of treatment with isoflurane, attenuated the degree of LV dysfunction after isoprenaline injection, as the degree of akinesia was lower in ISOFL 0, ISOFL 10, ISOFL 30 compared to CONTROL Figure . In a muIn this animal model of TCM, isoflurane treatment, when started early after induction of TCM, highly attenuated degree of LV apical akinesia. This was accompanied by a clearly improvement of survival. Isoflurane sedation in the ICU could be a beneficial strategy in patients suffering from hyper-adrenergic conditions.


Myocardial black blood (BB) T2* relaxometry at 1.5T provides robust, reproducible and calibrated non-invasive assessment of cardiac iron burden. In vitro data has shown that like T2*, novel native Modified Look-Locker Inversion recovery (MOLLI) T1 shortens with increasing tissue iron. The relative merits of T1 and T2* are largely unexplored. We compared the established 1.5T BB T2* technique against native T1 values at 1.5T and 3T in iron overload patients and in normal volunteers.A total of 73 subjects  were recruited, comprising 20 healthy volunteers (controls) and 53 patients . Single mid-ventricular short axis slices were acquired for BB T2* at 1.5T and MOLLI T1 quantification at 1.5T and 3T.0.282 at 1.5T (R2 = 0.717), and y =406 · x0.294 at 3T (R2 = 0.715). Measures of reproducibility of T1 appeared superior to T2*.In healthy volunteers, median T1 was 1014 ms (full range 939–1059 ms) at 1.5T and modestly increased to 1165ms (full range 1056–1224 ms) at 3T. All patients with significant cardiac iron overload  had T1 values <939 ms at 1.5T, and <1056 ms at 3T. Associations between T2* and T1 were found to be moderate with y =377 · xT1 mapping at 1.5T and at 3T can identify individuals with significant iron loading as defined by the current gold standard T2* at 1.5T. However, there is significant scatter between results which may reflect measurement error, but it is also possible that T1 interacts with T2*, or is differentially sensitive to aspects of iron chemistry or other biology. Hurdles to clinical implementation of T1 include the lack of calibration against human myocardial iron concentration, no demonstrated relation to cardiac outcomes, and variation in absolute T1 values between scanners, which makes inter-centre comparisons difficult. The relative merits of T1 at 3T versus T2* at 3T require further consideration. Since a biological pathway for body iron surplus elimination is non-existent in humans, excess iron from gut absorption or transfusion is stored in a stable hemosiderin form but once this storage capacity is exhausted free iron can be left unbound. This free ferrous iron can consequently catalyse cellular Fenton reactions and create highly reactive hydroxyl radicals causing mitochondrial dysfunction,  apoptosiCardiovascular magnetic resonance (CMR) T2* assessment of myocardial iron burden at 1.5 Tesla (T)  plays a Against this background of substantial gains in clinical management of transfusion dependent patients over the last 15 years are new advances in hardware and software technology. Increasingly 3T scanners are entering clinical practice and these may offer advantages over conventional 1.5T magnets for iron burden quantification. Unfortunately, 3T CMR may suffer from increased artefacts making myocardial T2* assessment challenging, particularly in patients with a high degree of iron overload , 15. AnoA total of 53 consecutive subjects were prospectively recruited over a 6 month period from September 2012 to February 2013 from referrals for cardiac siderosis screening or follow-up. A wide dynamic range of iron loading was present in the patient group and was a realistic reflection of our population. Patients had successive CMR scans at both 1.5T and at 3T. A group of 20 matching healthy volunteers was also scanned. Exclusion criteria were: 1) claustrophobia, 2) metallic implants or permanent pacemaker and 3) inability to hold recumbent position for >15 minutes. The study protocol was approved by the local ethics committee, and all subjects gave written informed consent.The BB T2* and MOLLI T1 CMR protocol was performed on a 1.5T Sonata scanner, and then a 3T Skyra scanner .At 1.5T, a four-element cardiac phase-array coil was used. After routine localizer acquisitions, an ECG gated single breath hold multi-echo sequence was acquired at a single mid-ventricular short axis slice with a 10 mm thickness at eight separate echo times . The BB sequence used a flip angle of 35°, a matrix of 128 X 256 pixels a field of view (FOV) of 40 cm, repetition time of 20 ms between each radiofrequency (RF) pulse and a sampling bandwidth of 810 Hz per pixel. Furthermore, for the black blood preparation, double inversion pulses were applied at the R wave trigger and the inversion time (TI) was set to extend into diastole.The sequence used for myocardial T1 evaluation has been reported elsewhere . In brieThe myocardial T2* quantification with truncation has been described elsewhere . In brieT2* was subsequently transformed into its reciprocal R2* according to the equation:Curve fitting was performed with the truncation method . The conAn identical mid-ventricular septum region of interest (ROI) was used for T1 quantification. Delineation of the epicardial and endocardial borders was done on the T1 maps. The interventricular septum was subsequently isolated for quantification. Careful consideration was given not to include blood-pool or artefacts in the septal ROI. T1 maps were automatically derived as described previously, –27 by fiWhere SI is the signal intensity at a specific inversion time (TI), and T1 can be approximated:When required, T1 was subsequently transformed into its reciprocal R1 using a similar equation:No gadolinium contrast agent was administered. A single, blinded, experienced observer performed analysis for BB T2* at 1.5T, and MOLLI T1 at 1.5T and 3T.A group of 20 patients was randomly selected for inter-observer, intra-observer and inter-study variability measurements. These patients had levels of myocardial siderosis that covered the entire range of the disease (from absent to severe iron overload). For intra-observer variability, the same investigator blindly reassessed myocardial T1 and T2* on 2 occasions a month apart. For inter-observer variability, two highly experienced investigators separately and blindly reported T1 and T2* for each patient. Finally, these 20 patients underwent a repeated cardiac T1 scan at 1.5T and at 3T one hour after completing the previous scan. The same investigator randomly and blindly re-evaluated T1 in these subjects to obtain inter-study variability.U test. Association between T2*, T1, R2* and R1 values at different field strengths were evaluated with a linear or non-linear regression when appropriate. Coefficients of variation (CoV) and intra-class correlation (ICC) with 95 % confidence interval (CI) analysis were conducted to assess inter- and intra-observer variability in addition to inter-study variability of T1 values. For ICC, an alpha two-way mixed model with absolute agreement analysis was used. Finally, Bland-Altman plots were generated to further describe the reproducibility of T1 measurements at 1.5T and at 3T  and the full range of values was 939–1059 ms. In accord with previous intellectual considerations defining the lower limit of normal of T2* to represent the onset of significant iron loading, so that low values should rarely be seen in the normal population, we used the lowest T1 observed in normals of 939 ms at 1.5T as the lower limit of normality for the scanner and sequence that was used in this report. The median T1 at 3T was longer at 1165 ms [1119–1194] and the full range of values was 1056–1224 ms. Using the same argument as above, we therefore set the lower limit of normal for significant iron loading as being the lower limit of the normal range at 3T which was 1056 ms.0.282 (R2 = 0.717). All patients with cardiac iron overload (T2* <20 ms at 1.5T) had T1 values at 1.5T below the lower limit of normal T1 values in the control cohort (939 ms). Only four patients had T2* values >20 ms at 1.5T and had T1 values at 1.5T below the lower limit of T1 values found in the present normal cohort. As shown in Fig. 2 = 0.772).The relation between T1 and T2* at 1.5T is shown in Fig. 0.294 (R2 = 0.715). All patients with a significant degree of iron overload (T2* <20 ms at 1.5T) had a T1 values at 3T <1056 ms . A total of seven patients with normal T2* values at 1.5T had T1 values below 1056 ms at 3T. The association between R1 at 3T and R2* at 1.5T is shown in Fig. 0.293 (R2 = 0.715).The relation between T1 at 3T and T2* at 1.5T is shown in Fig. The intra-observer, inter-observer and inter-study variability of T1 at 1.5T and at 3T is shown in Table These data show reasonable correlations between cardiac T1 and cardiac T2* measures across a wide range of cardiac iron loading, but with significant scatter, and there is reasonable agreement with our previous data comparing T1 and T2* at 1.5T in thalassaemia patients,  and withThe advantages of T1 CMR include: A) At low iron levels, T1 is less affected by non-iron influences that affect T2* measurements, making T1 appear to be more suitable for clinical conditions where low iron levels may be responsible for disease pathogenesis; B) T1 has good inter-study reproducibility, which appears superior to T2* which may be of benefit for longitudinal patient follow-up and clinical trials. Counterbalancing views to these advantages are: A) The dominant pathologies associated with iron dysfunction by prevalence are those involving substantial iron overload  and for these conditions there is rather little obvious merit in defining iron levels moving within the non-significant range, when movements of T2* are robustly identifiable in the low-risk mild to moderate iron overload range of cardiac T2* between 10–20 ms. Nonetheless, some more unusual pathologies are apparently associated with iron dysfunction at low iron levels, , 30 for It has also been suggested that cardiac T1 might have improved utility for identifying patients with cardiac iron loading through a better delineation of the lower limit of normal for cardiac iron loading . It is dAnother potential advantage of T1 measurement of iron concentration which is identified in this paper, is the use of T1 at 3T. There has been substantial increase in the use of 3T for MR of the brain and musculoskeletal system, and a number of centres no longer have 1.5T scanners available causing problems for thalassaemia patients. The two most likely solutions to this problem are to calibrate T2* at 3T against 1.5T, on which progress has already been made, , 15, 35 A problem associated with the current implementation of T1 mapping is the variation of absolute values of T1 between sequences and scanners. This is illustrated in this paper where the median value of T1 at 1.5T in normal subjects was 1014 ms which compares with the mean of 968 ms from Sado et al.  Sado useSome further technical issues need to be considered in the use of T1 for iron assessment. Diffuse fibrosis raises native T1, whereas myocardial iron lowers native T1. There is debate about the prevalence of myocardial fibrosis in thalassaemia, , 42 but Further issues with the validation of T1 also exist, that are troublesome. Clearly this paper and others have shown that T1 can be used to measure tissue iron concentration, but in humans the only comprehensive validation in the heart has been performed using T2*. Myocardial T2* measured at 1.5T is firmly established as the gold standard measurement of myocardial iron concentration,  and thisNative T1 mapping at 1.5T appears to be promising as a tool to evaluate myocardial iron. However, considerable further work is required in standardisation and transferability between scanners and centres, as well as in understanding whether T1 can be used as a substitute for T2* in the absence of direct studies of calibration and linkage with cardiovascular outcomes. The established practice worldwide of using T2* at 1.5T is unlikely to change in the near future without persuasive additional arguments. However, T1 measurements at 3T may prove useful where T2* measurements can be problematic.


We aimed to determine if myocardial perfusion (MP) is decreased in young patients with hypertrophic cardiomyopathy (HCM) and first grade relatives without hypertrophy (subjects at risk) during adenosine induced myocardial hyperemia. Furthermore, we wanted to investigate if such a decrease was associated with diastolic dysfunction.Twelve controls (22.8 ± 4.5 years), fourteen subjects at risk (18.9 ± 3.8) and ten HCM patients (22.3 ± 6.4) were examined using echocardiography and cardiovascular magnetic resonance (CMR) at rest and during hyperemia (adenosine 140 μg/kg/min). Patients with left ventricular outflow tract obstruction were excluded from the study. Myocardial perfusion was calculated as the ratio of coronary sinus flow and left ventricular mass (LVM) from CMR. Myocardial fibrosis was assessed using late gadolinium enhancement. Diastolic function was quantified using both echocardiography and CMR. The Mann-Whitney test was used to compare the groups and results were considered significant if p < 0.05. Results are presented as mean ± SEM if not otherwise stated. The study was approved by the Ethical Board and informed consent was obtained.There was no significant difference in MP (ml/min/g) at rest in controls, subjects at risk and HCM patients . During hyperemia, MP was similar in controls and subjects at risk . Even when fibrosis was excluded from LVM the MP was lower in HCM patients compared to the other groups. Two subjects showed mild diastolic dysfunction (E/e' = 16), otherwise none of the investigated subjects showed marked diastolic dysfunction (E/e'<15).Young HCM patients show decreased MP during hyperemia in non-fibrotic myocardium compared to controls even without diastolic dysfunction. These findings indicate that microvascular disease may be the cause of decreased MP in young patients with HCM. Funding. The Heart and Lung foundation, Region of Skane, Lund universityThe Heart and Lung foundation, Region of Skane, Lund University.


To validate an automatic algorithm for offline T2* measurements, providing robust, vendor‐independent T2*, and uncertainty estimates for iron load quantification in the heart and liver using clinically available imaging sequences.A T2* region of interest (ROI)‐based algorithm was developed for robustness in an offline setting. Phantom imaging was performed on a 1.5 Tesla system, with clinically available multiecho gradient‐recalled‐echo (GRE) sequences for cardiac and liver imaging. A T2* single‐echo GRE sequence was used as reference. Simulations were performed to assess accuracy and precision from 2000 measurements. Inter‐ and intraobserver variability was obtained in a patient study (n = 23).Simulations: Accuracy, in terms of the mean differences between the proposed method and true T2* ranged from 0–0.73 ms. Precision, in terms of confidence intervals of repeated measurements, was 0.06–4.74 ms showing agreement between the proposed uncertainty estimate and simulations. Phantom study: Bias and variability were 0.26 ± 4.23 ms (cardiac sequence) and −0.23 ± 1.69 ms (liver sequence). Patient study: Intraobserver variability was similar for experienced and inexperienced observers (0.03 ± 1.44 ms versus 0.16 ± 2.33 ms). Interobserver variability was 1.0 ± 3.77 ms for the heart and −0.52 ± 2.75 ms for the liver.Magn Reson Med 75:1717–1729, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance.The proposed algorithm was shown to provide robust T2* measurements and uncertainty estimates over the range of clinically relevant T2* values. Magn Reson Med, 2015. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  Organ failure caused by iron overload is a major cause of death in patients with iron load disease. Accurate quantification of organ iron load has been shown useful in tailoring the therapy for such patients Different methods for quantification of iron load by MR T2* are generally used Validated inline methods may simplify iron load measurements and improves clinical availability. However, robust offline T2* methods may have an important role in multivendor settings. The maximum likelihood estimate (MLE) method Therefore, the purpose of this study was to introduce and validate an automatic algorithm for offline T2* measurements also providing uncertainty estimates for robust quantification of iron load in the heart and liver, optimized for a wide range of T2* values. The method was validated in numerical simulations, in a phantom study and was applied to cardiac and liver MR imaging in patients with known or suspected iron load disease.Patients were included at two centers. The protocol and procedures comply with the Declaration of Helsinki, and were approved by the local research ethics committees. All studies were performed using 1.5 Tesla (T) Philips Achieva systems . An overview of typical sequence parameters used in this study is provided in Table SegmentWe propose a new algorithm for T2* estimation in magnitude MR images called ADAPtive T2* estimation from combined Signal models (ADAPTS). It is a ROI‐based algorithm adapting the curve‐fitting approach to balance accuracy and precision. All image processing including the proposed algorithm was developed using MATLAB  and was implemented in the medical image analysis software An overview of the algorithm is provided in Figure S depends on the TE, the proton density PD and an offset parameter C which approximates the noise‐floor. Compared with a two‐parameter monoexponential, shown in Eq. [2], The increased degree of freedom of a three‐parameter fit enables closer approximation of the measured signal The signal T2*^ in the remainder of this section) as the final T2* value, ADAPTS uses the initial fit for data‐truncation. TEs exceeding P1*T2*^, where P1 is a nonzero constant, are excluded from the analysis and T2* is re‐estimated from a two‐parameter monoexponential fit (Eq. [2]) of remaining TE images, similar to the automatic truncation algorithm proposed by He et al P2, to proceed with the truncation method. If the number of valid TEs is below P2, ADAPTS assumes the number of remaining data points is insufficient for robust T2* estimation and switches to a noise‐correction approach, similar to the M2NCM method (Second‐Moment Noise‐Corrected Model), proposed by Feng et al This, however, makes three‐parameter models inherently sensitive to noise and over fitting to the obtained data points. The estimated offset parameter is used to approximate the noise plateau and instead of reporting the obtained T2* estimate , σ is the noise standard deviation and L the number of receiver coils in use. As previously proposed P1 and P2 were optimized in the phantom study and in simulations, described in more detail below.Here, M denotes the measured signal contaminated with noise, To estimate uncertainty of the obtained T2* value, T2* was calculated in nonoverlapping, equally sized subregions. From the subregion ensemble of T2* values the 95% confidence interval (CI) size was estimated. The size of the subregions were defined as a fixed percentage of the ROI size to produce a near‐constant number of T2* values for each CI estimate. Due to the reduced number of pixels in the subregions compared with the ROI, the standard error of the mean (SEM) will increase for the pixel averages used for subregion T2* estimation. Assuming statistically independent pixels and a linear error propagation from the data‐points to the T2* estimate, a correction factor may account for the difference in standard error:N denotes the number of independent pixels in the ROI and n denotes the number of independent pixels in a subregion. Although this measure does not directly correspond to the precision of the full‐ROI T2* estimate, it serves as an approximation which is further affected by T2* homogeneity and varying noise levels within the ROI. Compared with pixelwise T2* estimates, subregion T2* results in improved precision due to pixel averaging, which more closely resembles the original ROI estimate. ADAPTS reports the T2* 95% CI together with the coefficient of variation . Based on the obtained CoV estimate the user may be advised to adjust the ROI delineation.Here, Numerical simulations were performed to assess accuracy and precision of ADAPTS and to evaluate reliability of the uncertainty estimate in relation to known T2* values. RSS reconstruction of 1, 6 and 32 receive‐coils was simulated with identical monoexponential T2* decay on the real and imaginary part of a complex signal. Zero‐mean Gaussian noise with predefined standard deviation (SD) σ was added to each channel and the magnitude signal was created by the root sum of squares operation:Ml denotes the magnitude signal of receive‐channel l, Im denotes the imaginary signal component and Re the real component. The SNR was defined as 0S/σ, where 0S is the signal intensity at TE = 0. The mean of 40 independent signals was averaged before curve‐fitting to simulate ROI‐averaging. A T2* range of 1–50 ms for SNR = 15 was simulated. TEs corresponding to the clinical T2* cardiac and liver sequences were used with TE ranges of 2.5–25 ms and 1–20 ms, respectively. T2* values below the minimum TE were not simulated for either sequence. This resulted in simulated T2* ranges for cardiac and liver of 2.2–50 ms and 1–50 ms, respectively. Simulations were repeated 2000 times to evaluate accuracy and precision of ADAPTS. From the 2000 repetitions, the mean and 95% CI of the ADAPTS T2* calculation were computed for each simulated T2* value.In addition to ADAPTS, a two‐parameter version of the noise correction method M2NCM was simulated which takes the true noise standard deviation as input. This enabled a comparison with a near‐optimal method. The optimized parameters P1 and P2, previously derived from phantom measurements, were refined in simulations and accuracy and precision of ADAPTS was compared with each of the two included signal models (two‐parameter automatic truncation and three‐parameter noise‐correction methods).Reliability of ADAPTS uncertainty estimate was evaluated by comparing a total of 2000 CI estimates to the CI of the 2000 ADAPTS T2* ROI estimates. This procedure was repeated for multiple subregion sizes and ROI‐sizes to optimize the CI estimates. Simulated ROI‐sizes and region‐sizes was  pixels and . Simulated ROI‐size for evaluating the optimal subregion size was 40 pixels.Twelve 300 mL gel‐phantoms with T2*/T1 values corresponding to iron overloaded myocardium Phantom imaging was performed using a six‐channel SENSE head‐coil. Accuracy and precision of ADAPTS were evaluated in two clinically used, single breath‐hold, multiecho gradient‐recalled echo (mGRE) sequences for heart and liver imaging.1) to allow full longitudinal recovery between excitation pulses. T1 was measured in all phantoms with a Modified Look‐Locker Inversion‐Recovery (MOLLI) sequence using a 5(3s)3 scheme.Accuracy of the clinical T2* sequences combined with ADAPTS was evaluated by comparison with a single‐echo gradient‐recalled echo (sGRE) reference sequence with , in three phantoms for each sequence, and with target T2* selected to represent typical values seen in clinical imaging:  and  for the heart and liver sequences. All repetitions for a single phantom were performed in the same session, in direct sequence with a minimum pause of 7 s between repetitions. In addition, the repeated measurements were used to validate the proposed ADAPTS uncertainty estimate by direct comparison with the CIs obtained from the 120 repetitions, and the effect of varying the ADAPTS parameters The sGRE reference sequence used a flip angle of 50° and typical TEs = . The mGRE sequence for liver imaging used a flip angle of 20°, a repetition time of 38 ms, and TE =  and the mGRE sequence for cardiac imaging used a black blood DIR preparation scheme, a parallel imaging factor of 2 (SENSE), a flip angle of 20°, a repetition time of 26 ms and TEs = . The MOLLI sequence used a repetition time TR/TE of 2.4/1.11 ms, and a flip angle of 35°. The shim volume was placed equivalently for all sequences in all phantoms and a simulated electrocardiogram was generated with a constant heart rate of 60 bpm. Further sequence details are found in Table 2 ROI. T2* from the sGRE sequence was determined from the acquired magnitude images, by a two‐parameter monoexponential fit of the pixel‐mean using a near‐identical ROI compared to the one used for T1 measurements (ROI position was approximated due to subtle differences in resolution). The Nelder Mead Simplex algorithm (21) was used for nonlinear optimization and the initial starting values were obtained from the WLSL method 2 ROI using inline MLE maps T1 in each phantom was measured from the provided inline T1 maps of MOLLI within a 3.1 cmTwenty‐three patients  with known or suspected iron load disease were included in this study. Written consent was given by the patients or, in case of minors, their guardians. MR images for determination of T2* values were collected as part of routine clinical iron load assessment.For patient imaging, clinical mGRE sequences were used with a 5‐ or 32‐channel cardiac coil in two centers. Two similar sequences were used, one optimized for cardiac and one for liver imaging Table . The twoTo assess cardiac iron a mid‐ventricular slice was acquired using the clinical cardiac sequence. A black‐blood double‐inversion recovery (DIR) prepulse was used to decrease measurement error induced by blood contamination, and to enhance myocardial borders Online reconstruction of T2* maps from an inline MLE method Data were anonymized and randomized for blinded analysis. The ROIs were manually drawn at two occasions, by two observers  for analysis of intra‐ and interobserver variability, also accounting for user experience.The ROIs were drawn in the acquired images for evaluation of T2* in full thickness myocardial septum and in a homogenous area of the liver parenchyma, anteriorly if not prevented by vessels or susceptibility artifacts. These exact ROIs were copied to the inline‐constructed MLE T2* map to avoid measurement differences related to ROI delineation. The MLE image was reconstructed from the very same acquisition as the ADAPTS analysis. To assure adequate ROI placement for both ADAPTS and MLE the curve fit using ADAPTS was visually inspected and the ROI redrawn in case of obvious incorrect placement. Software advice based on CoV for re‐evaluation of delineation was also considered. Motion correction was not performed in the current study, as motion between images acquired within the same breath‐hold was not detected.P‐value < 0.001 was used to define statistical significance.Statistical analyses were performed in MATLAB . By default, statistical measures for the patient study were obtained from the experienced observer. Bias and variability are presented as mean ± 1.96 SD and median (range) was used where appropriate. Bland‐Altman analysis Results from the simulation study are shown in Figures The simulation results for ADAPTS uncertainty estimates are shown in Figure The T2* and T1 ranges of the 12 phantoms were 2.20–40.24 ms and 470–1012 ms according to the T2* reference standard (sGRE) and MOLLI T1. T1 values are in the range of myocardial tissue. T2* of the six phantoms used to evaluate precision was 2.3, 3.9, 7.2, 7.7, 13.2, and 18.3 ms, obtained from the inline MLE method. The results from the phantom validation of ADAPTS uncertainty estimates for both clinical sequences are shown in Figure The results from the parameter optimization of ADAPTS are shown in Figure All images and reconstructed T2* maps were of adequate quality for determination of T2* in both heart and liver. In one patient, however, the cardiac image quality was visually suboptimal due to breathing artifacts, albeit adequate for analysis, and was, therefore, included in further analysis. In this patient we also found the largest intraobserver difference of 3.96 ms (11%). The range of cardiac and liver T2* was 9.6–51.2 ms and 0.6–25.0 ms, respectively, using the ADAPTS method. The range of obtained uncertainty estimates for the ADAPTS method, expressed as coefficient of variation , was 0.05–0.46 for cardiac and 0.01–0.27 for liver measurements. The number of pixels within the drawn ROI:s ranged from 53–561 pixels for liver images and 44–358 pixels for heart images.P < 0.0001 for the null‐hypothesis). However, poor goodness of fit was found (r2 = 0.43).The ADAPTS and the MLE methods showed good agreement determining T2*, resulting in a bias and variability with limits of agreement of −1.28 ± 2.19 ms for the cardiac sequence; −0.13 ± 0.38 ms for the liver sequence and −0.71 ± 1.94 ms for the cardiac and liver sequences combined  and mean bias (bottom) for the simulated parameter values for the cardiac sequence TEs and the right column shows the corresponding plots for the liver sequence TEs. In all graphs, the solid lines and dashed lines represent simulations using one and six coils, respectively. The line marked with triangles indicates 32 simulated coils. The dotted vertical line shows the selected parameter set, corresponding to P1 = 4.5 and P2 = 9. A P1 value was selected by mainly considering stability, as shown in Figure 4.Figure S2. Optimization of the uncertainty estimate in simulations with relative subregion sizes of 4–10%. Top row shows confidence intervals of the uncertainty estimates in simulations and the impact of varying simulated ROI‐size and subregion size percentages. Bottom row shows Mean bias of CI estimates with the left and right column showing the results from the cardiac and liver sequence TEs, respectively. Decreasing subregion percentages and increasing the ROI size improve precision of CI estimates. For the liver sequence TEs, bias is consistently decreased when the subregion size is reduced. The observed behavior is also seen in Supporting Figure S3.Figure S3. Optimization of the uncertainty estimate in simulations with relative subregions sizes of 12–25%. Top row shows confidence intervals of the uncertainty estimates in simulations and the impact of varying simulated ROI‐size and subregion size percentages. Bottom row shows Mean bias of CI estimates with the left and right column showing the results from the cardiac and liver sequence TEs, respectively. Decreasing subregion percentages and increasing the ROI size improve accuracy and precision of CI estimates. The order of accuracy and precision among simulated subregion sizes is preserved over the evaluated ROI‐size interval. This may suggest that the relative percentages used to define the subregion size is robust to changes in ROI size. The observed behavior is also seen in Supporting Figure S2.Click here for additional data file.