Patients with single ventricle physiology are at increased risk for developing liver fibrosis. Its extent and prevalence in children with bidirectional cavopulmonary connection (BCPC) and Fontan circulation are unclear. Extracellular volume fraction (ECV), derived from cardiovascular magnetic resonance (CMR) and T1 relaxometry, reflect fibrotic remodeling and/or congestion in the liver. The aim of this study was to investigate whether pediatric patients with single ventricle physiology experience increased native T1 and ECV as markers of liver fibrosis/congestion.Hepatic native T1 times and ECV, using a cardiac short axis modified Look-Locker inversion recovery sequence displaying the liver, were measured retrospectively in children with BCPC- and Fontan circulations and compared to pediatric controls.n = 62, 11.4 ± 4.4 years, T1 762 ± 64 ms) versus BCPC patients . Both cohorts had higher T1 than controls . ECV was 41.4 ± 4.8% in Fontan and 36.4 ± 4.8% in BCPC patients, respectively (p = 0.02). In Fontan patients, T1 values correlated with exposure to cardiopulmonary bypass time , systolic and end diastolic volumes  and inversely with oxygen saturations and body surface area . There were no demonstrable associations of T1 or ECV with central venous pressure or age after Fontan.Hepatic native T1 time were increased in Fontan patients  contains supplementary material, which is available to authorized users. The Fontan operation, introduced over 40 years ago, and its permutations place the systemic and pulmonary circulations in series rather than in parallel in patients with functionally univentricular hearts , 2. FontNative T1 times and extracellular volume fraction (ECV) derived from cardiovascular magnetic resonance (CMR) T1 relaxometry, often referred to as ‘T1 mapping’, are non-invasive markers of diffuse tissue fibrosis increasingly applied to the myocardium –9. More In the present study we aimed to investigate the feasibility of T1 mapping in the liver in pediatric Fontan and BCPC patients on routinely performed CMR. We hypothesized that CMR markers of extracellular volume (ECV) expansion are increased in patients with single ventricle physiology and associated with their hemodynamics.In this retrospective cross-sectional cohort study, consecutive pediatric patients with BCPC and Fontan-type palliations who underwent CMR between April 2014 and March 2018 were included. During that interval T1 relaxometry was routinely included in the CMR protocol. Patients with a non-diagnostic T1 relaxometry acquisition pertaining to the liver were excluded. Only the latest exam was included when more than one CMR scan were eligible.Demographic, clinical, and surgical Information were retrieved from patient charts. Cumulative cardiopulmonary bypass- (CPBT), circulatory arrest- (CAT) and cross-clamp times (CCT) were recorded. The patients’ oxygen saturations and blood pressures at the time of CMR , serum biomarkers of hepatic function and hemodynamic data from cardiac catheterization as long as performed within 6 months of the CMR, were also retrieved.Synthetic liver dysfunction was defined as an albumin concentration below the normal range in patients without protein losing enteropathy (PLE) and/or an elevation of the international normalized ratio (INR) above 1.2 in patients who were not receiving warfarin. Metabolic liver dysfunction was indicated by any of the following values outside of the normal range for age: unconjugated bilirubin, aspartate transaminase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase.As a control group, patients examined between April 2014 and March 2017, with the same T1 relaxometry protocol for a family history of arrhythmogenic right ventricular cardiomyopathy or non-specific chest pain referred for anatomical coronary artery imaging were included, as long as their entire work-up was negative.All patients and controls underwent CMR examinations on a 1.5 T system . The detailed protocol has been published elsewhere . In brieAll T1 mapping analyses were conducted by a single observer (CdL). T1 relaxation times were extracted from the MOLLI acquisitions using commercially available software : Corresponding regions of interest (ROIs) were drawn on each of the eight motion corrected source images. T1 times were derived based on post-inversion recovery times and signal intensities, using a curve fitting algorithm.Portions of the right and left lobes of the liver were visible on the mid-ventricular short axis slice. T1 relaxation times were measured by tracing three regions of interest (ROI): ROI 1, near the diaphragm, ROI 2, in the middle near the hepatic hilum, and ROI 3, in the caudal and peripheral part of the liver. All ROIs were traced to avoid major vessels, the gall bladder and hepatic surface  for observer variability. The same observer re-analyzed the same sample after an interval of at least 5 weeks blinded to the original results.The same software platform  was used for the myocardial volumetric measurements: both ventricular chambers were contoured as one chamber as long as they were connected via a ventricular septal defect (VSD) and / or both chambers ejected into the (neo-) aorta. Otherwise, only the dominant ventricle was contoured.In addition, flow in the ascending and descending aorta, superior vena cava and the pulmonary arteries and veins were analyzed. Aorto-pulmonary collateral (APC) flow was calculated by subtracting total pulmonary arterial flow from the sum of the pulmonary venous flows.Continuous variables are presented as means ± standard deviation (SD) if normally distributed and otherwise as medians and ranges. Categorical variables are expressed as counts and percentages of the total. Student’s t tests, Wilcoxon Rank-Sum tests or and analysis of variance (ANOVA) with post-hoc Tukey test for multiple comparisons, when appropriate, were used for comparisons between patient groups for continuous variables and Fisher’s exact tests for categorical variables.p-values < 0.01 on univariate testing. P-values < 0.05 were considered statistically significant. Intra- and inter observer reproducibility’s were assessed by Bland-Altman analyses [Correlations between continuous and categorical parameters were assessed using univariate regression analysis. A multivariate regression model was performed for variables with a significant number of patients and with analyses . StatistPatient characteristics including clinical parameters are presented in Table Serum liver function testing was available in 31 Fontan patients and only two had all hepatic biomarkers within the normal range. None of the patients had severe metabolic or synthetic dysfunction. Twenty-three of 31 Fontan patients (74%) had mildly abnormal parameters of metabolic hepatic function as evidenced by bilirubin, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase and gamma-glutamyl transferase. Fourteen of 27 Fontan patients (52%) had mildly deranged synthetic function with increase in INR (up to 1.8) and decrease in albumin .Native T1 and ECV differed between the three ROIs  and for patients . This difference was attributed to the lower oxygen saturations in hepatic venous as compared to systemic ventricular blood.Blood pool native T1 values, were significantly higher in the ventricular blood pool than in hepatic venous blood, for controls  for patients (BCPC and Fontan combined) and 58.1 ± 12.6% and 32.1 ± 4.8% (p < 0.001) for controls. For controls, the two groups did not differ significantly with regards to their gender, age composition or their hepatic native T1 times . We suspect that the ECV measurements in the gadobenate dimeglumine group were falsely elevated due to the partial biliary excretion (3–5%) of the drug, and consequently, ECV was computed only for patients who had received gadobuturol.Thirty-two out of 82 patients received gadobenate dimeglumine (‘Multihance’) and the remaining 50 patients (33 Fontan and 17 BCPC patients) had gadobuturol (‘Gadavist’). Of the 19 controls who received gadolinium, 15 had gadobenate dimeglumine and four gadobuturol. Liver ECV was markedly higher in subjects who had received gadobenate diglumine as compared to gadobuturol: 45.4 ± 4.0% vs. 39.8 ± 5.2% (p < 0.001 for both groups) . ECV was not significantly different for SLV and SRV (p = 0.1) (Table p = < 0.001). Both T1 and ECV were lower in SLV BCPC patients than in SLV Fontan patients .Native T1 times in BCPC and Fontan patients were elevated as compared to controls, (ps) Fig. . Native The comparisons between Fontan patients with normal and abnormal hepatic (synthetic or metabolic) hepatic function regarding T1 and ECV were underpowered due to the low number of patients with available biochemistry data.p = 0.02, CI ), with total CCT ) and with total CAT ). Native T1 correlated with end-systolic and end-diastolic volumes  and (0.01–0.8) respectively) and with APC flow ). Native T1 correlated inversely with SaO2 and body surface area  and (-89.50 − -3.35) respectively).In Fontan patients, T1 values correlated weakly with the sum of all previous CPBTs  had similar T1 and ECV as the remainder of Fontan patients.There were no correlations of liver T1 or ECV with ventricular end-diastolic, and central venous pressures. However, the statistical power for these analyses was low due to the modest sample size. Patients with a patent Fontan fenestration  gadolinium contrast agent with even partial biliary excretion must be avoided, b) hepatic venous and left ventricular blood pool T1values differ and c) averaging multiple ROIs is a suitable strategy to characterize liver ECV and T1 in light of heterogeneously distributed tissue changes in the Fontan population.Liver fibrosis is an increasingly recognized complication in older Fontan patients but little is known about the severity of hepatic fibrotic remodeling in young individuals with single ventricle physiology. CMR T1 relaxometry presents an opportunity to measure the degree of extracellular volume expansion non-invasively. The current study helped us refine the technique of hepatic T1 relaxometry, shaping the methods in future studies. Our results offer the following novel insights into hepatic tissue changes:FALD constitutes important morbidity in patients with functionally single ventricles. It affects candidacy for cardiac transplantation and other palliative operations. Furthermore, liver cirrhosis predisposes to malignant transformation of liver tissue to hepatocellular carcinoma , 17–21. The challenge in monitoring hepatic fibrosis until recently lay within the lack of non-invasive techniques to detect and quantify the degree of remodeling. Liver biopsy is the diagnostic gold standard but invasive and not without risk. As such, it does not lend itself to serial examinations. Furthermore, due to the heterogeneous hepatic changes the sampled tissue may not be representative of the average degree of fibrosis , 23. MorCMR T1 relaxometry overcomes some of these limitations by providing non-invasive, quantitative tissue characterization with a spatial resolution in the millimeter range. In non-congestive adult chronic liver disease, native T1 times can discriminate between histologic fibrotic grades , 28, 29 Only pilot data in 16 adult Fontan patients yielded CMR T1 and ECV levels comparable to our cohort . In our Our results suggest that the etiology of hepatic changes is multifactorial: For example, exposure to cardiopulmonary bypass is associated not only with long-term myocardial, but also hepatic remodeling , 40. AnoFontan patients with an SRV revealed a trend towards higher liver T1 values than those with a SLV. Whether this difference is related to longer bypass and cross-clamp times, the worse ventricular performance or a less obvious risk factor in the SRV group remains to be determined.In keeping with other pediatric reports, markers of hepatic function revealed only mild perturbations of synthetic and metabolic performance in 52 and 74%, respectively, of the Fontan patients who underwent biochemistry testing. No reliable analysis of an association of serum markers with ECV or T1 could be performed due to small sample size. Previous histological studies highlight the poor reflection of early liver injury in serum markers, due to the liver’s remarkable ability to compensate for these tissue changes until their late stages , 33.The current study yields several important technical insights into liver T1 mapping and ECV analysis. Most importantly, gadolinium agents with even a small percentage of biliary secretion, such as gadobenate dimeglumine, are not suitable for the quantification of ECV because their concentration in the bile system falsely decreases post-contrast T1, leading to erroneously high ECV results.In contrast to previously published reports  our dataLiver fibrosis is known to be a geographically heterogeneous process. As a result, we found systematic regional differences in the sampled T1. Previous studies implied that portal venous hypertension progresses centripetally from the liver periphery , 39. As The technical challenges with hepatic MR relaxometry pertain mostly to ECV and its calculation. In the present study, ECV did not appear to add insights beyond what was apparent from native T1 analysis. Relying solely on T1 and foregoing ECV is attractive as it avoids the need for intravenous gadolinium as well as abbreviate scan and post-processing times. On the other hand, ECV has been demonstrated to be more comparable across scanner manufacturers, field strengths, and patient populations , 42. It .Several limitations of this study warrant discussion: 1.) Since, most control subjects received gadobenate dimeglumine which is biliarily excreted, there was no control group for hepatic ECV. 2.) The pediatric control group was older than the patient group, limiting the comparability between the groups. Furthermore, the BCPC group was more homogeneous in age than the Fontan group which may have accounted for broader range of T1 and ECV values among Fontan patients. This relatively wide spectrum may have obscured some of the differences between Fontan patients and controls. 3.) It is possible that postprandial conditions, not controlled for during this study, influences native T1 and ECV owing to differences in portal venous flow . 4.) GivIn this study of a large cohort of pediatric patients with single ventricle circulations, imaging biomarkers of fibrosis and/or congestion are elevated and particularly after the Fontan operation. These liver tissue changes are not clearly associated with Fontan pressure or ventricular systolic performance. Longitudinal studies are required to test the prognostic significance of these derangements. Pitfalls of ECV quantification are related to the use of gadolinium contrast with biliary excretion, blood pool T1 sampling regions, and the heterogeneity of liver remodeling.Additional file 1:Table S1. Inter region T1, ECV differences. Native T1 times and extracellular volume fraction (ECV) for the different ROIs 1–3 and the average of ROIs 1–3 with observer variation. (DOC 41 kb)


Morphologically, the cardiac characteristic of the disease, occurs as left ventricular hypertrophy, is accompanied by myocardial fibrosis. Cardiologists may come across these patients during clinical and instrumental evaluation in individuals with non-specific symptoms such as chest pain and arrhythmias, or after instrumental evidence of left ventricular hypertrophy/hypertrophic cardiomyopathy . A comprehensive cardiological work-up, including a cardiological visit, a baseline electrocardiogram (ECG) and imaging by both echocardiography (ECHO) and magnetic resonance (MRI) enables identification of the cardiac involvement in patients with a proven diagnosis of AFD. The heart involvement is present in up to 75% of AFD patients irrespective of their sex. Involvement includes ECG and echocardiography features which suggest AFD and not HCM. Cardiac imaging plays an important role in detecting this sub-type of cardiomyopathy, which, since 2001, has benefited from the introduction of the enzyme replacement therapy (ERT) in symptomatic and pre-symptomatic patients.The Anderson-Fabry disease  is a rare X-linked lysosomal storage disorder (Xq22.1) characterized by progressive renal failure, leading to morbidity through cardio- and cerebro-vascular involvement. Despite the classic phenotype, only cardiac involvement  is frequent in about 40% of male and 28% of female AFD patients, as reported by the Fabry Registry ( Many storage diseases are associated with left ventricular cardiac hypertrophy , and in presence of a normal renal function . As the A)post-mortem).Left ventricular hypertrophy. In adult patients, the electrocardiographic signs of LVH are present in more than 61% of males and 18% of females and are associated with repolarization abnormalities. The QRS duration is reported to be around 160–200 msec and the amplitude/duration product, in the 12-lead ECG, is correlated with the left ventricular mass, as measured both by MRI and pathological findings (B)PR interval. The involvement of conduction tissue, due to the progressive infiltration by Gb3, leads to the onset of arrhythmias, showing a characteristic electrocardiographic framework. Depending on age and progression of the disease, PR is shorter in affected males (up to 11%) . With prAt the baseline ECG, shorter PR intervals are often the first (and sometimes the only) signs of cardiac involvement due to reduction of the P-wave duration. Specific features include:A)EchocardiographyIVR, and E/SRIVR (SR(IVR) (P < .001) and E/SR(IVR) (P = .025) remained significantly different between patients with FD and controls, with sensitivity of 94% and specificity of 92% for SR(IVR) of 0.235 s(− 1) , while radial and circumferential diastolic function are not affected. Right ventricle involvement is largely parallel to the left ventricle, although it is interesting to note that the right ventricle develops fibroblast hypertrophy, as evaluated with cardiac magnetic resonance imaging [LV hypertrophy is the morphological characteristic of the disease, often accompanied by myocardial fibrosis. A concentric hypertrophy usually occurs in adulthood of AFD patients with fibrosis of the left-lateral wall of the LV. However, eccentric hypertrophy can be detected too, as a result of the thinning of the left ventricular back-lateral basal segment, due to prevalence of the fibrous substitution. A ‘binary’ aspect of the endocardium - first detected and described by Pieroni et al. , may evo imaging . SystoliB)Cardiovascular magnetic resonance or magnetic resonance imaging (CMR/MRI).CMR is helpful in diagnosing HCM by identifying areas of hypertrophy, not visualized by echocardiography, providing a differential diagnosis of HCM from other causes of LVH . InfiltrAnderson-Fabry disease, a rare X-linked disorder, is a systemic lysosomal disorder. AFD cardiomyopathy can mimic hypertrophic sarcomeric cardiomyopathy (HCM) or amyloid cardiomyopathy. Differential diagnosis, by multidisciplinary approach and by incorporating specific cardiac signs, has important therapeutic and prognostic implications because AFD patients have benefited from an enzyme replacement therapy (ERT) since 2001. Cardiac imaging plays an important role in detecting this peculiar disease in patients with cardiac septum/wall thickening, both in the classic AFD and in its cardiomyopathy variant (AFD cardiomyopathy) form, therefore, thanks to timely diagnosis, avoiding end-stage renal failure and heart failure.


Once surgical management is indicated, variation of Ebstein valve morphology affects surgical strategy. This study explored practical, easily measureable, cardiovascular magnetic resonance (CMR)-derived attributes that may contribute to the complexity and risk of cone reconstruction.A retrospective assessment was performed of Ebstein anomaly patients older than 12 years age, with pre-operative CMR, undergoing cone surgical reconstruction by one surgeon. In addition to clinical data, the CMR-derived Ebstein valve rotation angle (EVRA), area ratios of chamber size, indexed functional RV (RVEDVi) and left ventricular (LV) volumes, tricuspid valve regurgitant fraction (TR%) and other valve attributes were related to early surgical outcome; including death, significant residual TR% or breakdown of repair.Of 26 operated patients older than 12 years age, since program start, 20 had pre-op CMR and underwent surgery at median (range) age 20 (14–57) years. TR% was improved in all patients. Four of the 20 CMR patients (20%) experienced early surgical dehiscence of the paravalve tissue, with cone-shaped tricuspid valve intact; one of whom died.o, relative risk of dehiscence was 3.2 . Those with dehiscence had thickened, more tethered anterior leaflet edges , smaller pre-operative functional RVEDVi; , and were older . TR %, chamber area ratios and LV parameters were not different.A larger EVRA correlated with Carpentier category and was significantly related to dehiscence. If EVRA >60Comprehensive CMR assessment characterizes patients prior to cone surgical reconstruction of Ebstein anomaly. Pragmatic observation of larger EVRA, smaller RVEDVi and leaflet thickening, suggests risk of repair tension and dehiscence, and may require specific modification of cone surgical technique, such as leaflet augmentation.The online version of this article (10.1186/s12968-019-0546-3) contains supplementary material, which is available to authorized users. Ebstein anomaly of the tricuspid valve involves failure of delamination of the septal leaflet, and to a variable extent, failure of delamination of the inferior and anterior leaflets .However, the anomaly shows remarkable morphologic and physiologic heterogeneity. It is strongly associated with right ventricular myocardial disease, conduction tissue anomalies and left ventricular (LV) noncompaction .Cone reconstruction of the Ebsteinoid tricuspid valve is a complex surgery that aims to restore the anatomic position of the valve, with improved tricuspid valve competency through native, leaflet-leaflet apposition . AlthougThe success of da Silva’s surgery  and subsWith critical perusal of results in our centre over time, we noticed that the cone reconstruction was not successful in the early post-operative period, in a minority of patients. Although tricuspid valve regurgitation had been effectively improved, some adult patients experienced early surgical dehiscence and breakdown of the repair, within 30 days of surgery.Optimal case selection and patient-specific planning of surgical technique for this valve reconstruction appear to be crucial factors for success.The current classification systems and recent data regarding Ebsteinoid valves are useful for gauging severity of disease, –11 but tAlthough echocardiography is optimal for viewing valve leaflets and visualizing flow jets, cardiovascular magnetic resonance (CMR) can better characterize chamber volumes, 3-dimensional shapes and overall haemodynamics. CMR is not hampered by acoustic difficulties, and imaging views may be more easily standardized.However, characterizing the variability and complexity of Ebstein anomaly requires images with high temporal and spatial resolution. CMR scan acquisition time is prolonged. Moreover, post-processing for volume segmentation of the right ventricle (RV) uses significant time resource. The technique is reproducible in experienced hands , but canThis was a retrospective analysis of all patients older than 12 years, undergoing the cone reconstruction for Ebstein anomaly in our combined adult and paediatric centres. A single surgeon completed all the operations from 2009, up to the present date.This age-group selection was chosen because Ebstein patients needing intervention in infancy and early childhood more often have physiology that requires different strategies to those needing their initial intervention later in life. Many of the patients undergoing cone reconstruction younger than 12 years required a cavopulmonary anastomosis to supplement pulmonary blood flow. For standardization and consistency, we elected to exclude all younger patients to avoid bias due to extreme or surgically-altered physiology.Patients were also excluded from this analysis if their tricuspid valve was dysplastic in a manner that did not fit diagnostic criteria for Ebstein anomaly, if previous attempt at surgical tricuspid valve repair had been undertaken, or if they had not undergone routine pre-operative CMR assessment.Alternative Ebstein valve repair methods or primary tricuspid valve replacement was not undertaken in our centre during the surgical era of this cohort.The indications for cone reconstruction surgery were conventional, and were agreed at Unit multi-disciplinary team meetings. These included severe tricuspid valve regurgitation, progressive right atrial (RA) or RV dilatation, cyanosis, or development of symptoms of breathlessness or exertional intolerance . No otheInformed, signed consent for the use of anonymised CMR imaging data was obtained from all patients, or guardians of patients who were younger than18 years. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki  (GOSH R&D no 07CC02).Scanning was performed for patients without sedation, using a 1.5 Tesla CMR scanner . Anatomy was initially mapped using single-shot balanced steady state free precession (bSSFP) scout images in 3 radiological planes. Retrospectively gated, bSSFP cine images of the heart were planned and acquired in multiple planes, with each cine image acquired during a single breath-holding episode. The image planes included the vertical long axis of both LV and RV, the 4-chamber view, the LV and RV outflow tracts and the short axis; covering the entirety of both ventricles (9–12 slices). Additional transaxial cine images were acquired, in order to view the RV and tricuspid valve (TV) apparatus using at least 4 slices, evenly spaced in the transaxial plane between the level of the inferior (diaphragmatic) RV wall and the superior RV outflow tract.The vertical long axis view of the RV  was calculated) was planned from a 4-chamber or transaxial RV view, by placing a perpendicular slice passing through the centre of the native, right atrio-ventricular junction, parallel to the interventricular septum Fig. .Fig. 1ThThe bSSFP cine imaging was acquired using the following parameters: repetition time (TR) 42.6 ms, echo time (TE) 1.2 ms; flip angle 68°, slice thickness 6-10 mm, matrix 200 × 240, field of view 300-380 mm, and temporal resolution 20 true phases per cardiac cycle, acquired during a single breath-holding episode.3, TE/TR 2.08/32.0, flip angle 25°, encoding velocity 180-300 cm/s, 20 phases.Through-plane CMR phase-contrast flow quantification data were acquired at four positions: the ascending aorta, the main pulmonary trunk and in each branch pulmonary artery, proximal to the first branch. The flow-imaging plane was planned truly perpendicular to the vessel and acquired during breath-hold, using a velocity-encoded, retrospectively gated, spiral phase contrast CMR sequence . ScannerAll images were processed using an in-house plug-in for the open source DICOM software OsiriX  . HoweverAll of the post-processing was completed in a standardized manner, by experienced CMR reporting staff, with more than 10 years experience. Volume and flow measurements were indexed for body surface area and expressed in mL/m2.Assessment of LV and RV volumes was performed by manually tracing the endocardial borders of both ventricles at end-diastole and end-systole, using the short axis stack of cine images. Myocardial trabeculations and larger papillary muscles were excluded from the blood pool. The atrialised RV volume  was not differentiated from true RA volume, but was differentiated and excluded from the true, functional RV volume, by carefully tracing the border of the functional TV tissue. Therefore, the RV end-diastolic volume index (RVEDVI) refers to the body surface area (BSA)-indexed functional RV volume. This study did not attempt to segment and differentiate the RA chamber from the “atrialised” RV chamber, as this has the potential for significant subjectivity.During segmentation, all available long axis cine planes were used as reference indicators for accurate slice position. This segmentation allowed evaluation of biventricular end-diastolic volume (EDV) and end-systolic volume (ESV), and calculation of stroke volume (SV) and ejection fraction (EF) .Aortic and pulmonary flow volumes were measured from the phase contrast CMR data. This was segmented using a semi-automatic vessel edge detection algorithm with manual operator correction (OsiriX plugin).The tricuspid valve regurgitant fraction (TVRF) percent was calculated using the RV stroke volume and pulmonary artery (PA) forward flow volume, using the following equation: TVRF % = [(RVSV – PA forward flow) / RVSV] × 100.The (right atrium: rest of heart) area ratio was measured from the 4-chamber CMR image, using the principles of Celermajer et al. . AdditioThe EVRA was defined as the plane of systolic apposition of the tricuspid valve leaflets, when viewed using a 2-dimensional RV long axis (RVLA) cine image Fig. , 2, 3, 4The end-systolic frame was selected from the cine loop, and the EVRA was measured with the fulcrum of the angle positioned at the basal superior “hinge-point” of the valve in this cine view, anterior to the aortic valve. This is reminiscent of the observations and illustration made by Schreiber et al. These authors describe the rotation of the valve within anatomic specimens, with the fulcrum at the ventriculo-infundibular fold .The first axis of the angle was drawn from the inferior, right atrio-ventricular (coronary) groove, towards the fulcrum. The second axis was drawn from the fulcrum, through the systolic plane of valve coaptation, then towards the RV free wall . This systolic apposition plane was often best marked by the origin of the “vena contracta” of the TV regurgitant jet. The EVRA is the angle between these two axes. Figure The EVRA for each patient was measured twice, by each of two experienced, independent observers, who were blinded to each other’s and the surgical results at the time of analysis. Repeat measurements by both observers were undertaken after a 2–4 week interval.The surgical technique is explained in the introduction of this manuscript and has been previously described in detail . A partiearly death, within 30 days of surgeryearly dehiscence of the reconstructed valve apparatus, within 30 days of surgerysevere residual tricuspid valve regurgitationThe pre-defined short-term primary outcome measures wereThe CMR factors assessed were: Carpentier classification , EbsteinCategorical variables were expressed as proportions. Continuous variables were expressed as medians with full range.Graphpad Prism 7.0c  was used for statistical analysis and figures. Simple, non-parametric statistical tests compared the groups . Small numbers precluded valid use of multivariate regression methods. Bland-Altman methodology assessed inter-observer and intra-observer variability. The level of α considered for statistical significance was 0.05.The authors had full access to the data and take responsibility for its integrity. All authors have read and agreed to the manuscript as written.Between 2009 and May 2018, a total of 26 patients older than 12 years had undergone cone reconstruction of the native Ebstein tricuspid valve in our unit, having met conventional criteria for surgery.Six of these 26 patients were not examined with pre-operative CMR, and have been excluded from this analysis. These patients were operated primarily during the earlier years of this surgical program, and because of referral from other centres, had no authorization for CMR in addition to preoperative echocardiographic imaging. None of these 6 patients experienced a sub-optimal short-term surgical result. Therefore, with the established selection criteria, the cohort for this study included 20 patients .The CMR examinations were undertaken at a median (range) age 19 (13–56) years, and the surgery was undertaken at an age of 20 (14–57) years. The median (range) between pre-operative CMR and surgery was 0.8 (0–4) years. For one adult the time between CMR and surgery was greater than 18 months, but the essential valve structure does not change, and echocardiography had shown no significant changes during that time period, so this CMR data was included in the study.Table Of the whole group, the median (range) body weight at surgery was 68 (43–99) kg.Using imaging and surgical report, 6 patients were classified as Carpentier Type A, 9 Carpentier Type B and 5 Carpentier Type C .The EVRA was measureable in all patients. For all patients, the measured EVRA correlated with the Carpentier classification of valve anatomy, as classified by the imaging team and surgeon. However there is some overlap of EVRA between Carpentier grades. Illustrating this, a scatter diagram of the distribution of EVRA in the whole patient cohort according to Carpentier classification is given in Fig. Correlation of the EVRA with other quantitative CMR parameters, including functional RV end-diastolic volume, total RA area, RV EF and TV regurgitation was tested, but none were found significant in this limited cohort.o (70 o − 78 o) vs 51 o (20 o − 71 o) in the 17 patients without obvious thickening, p < 0.01.On assessment of cine images, three patients in this cohort exhibited prominent thickening of the anterior leaflet margin or edge. With thickened, rolled edges of the anterior leaflet, there seemed to be a greater number of leaflet attachments to the RV anterior wall, with less leaflet mobility Fig. . The EVRAmong patients with a small atrial septal defect (ASD), the EVRA was compared between patients with net right to left shunt, versus those with a net left to right shunt. The EVRA did not show a clear relationship with the presence of an ASD, or with the direction of shunt if a small ASD was present. Of the six patients with a small ASD, there was no difference of the EVRA in the three shunting right to left, compared to the EVRA of the three shunting left to right.o. The standard deviation was 3.2o with 95% limits of agreement being − 6o to + 7o.Using Bland Altman Methodology, we found reasonable agreement between experienced observers measuring the EVRA, Fig. a and b. o, with 95% limits of agreement being − 13o to + 25o. Therefore, observers tended to differ in angle measurements by up to 25 o degrees. The difference between observers was greatest when angle measurements were at the lower range of values; that is, less rotated valves.The standard deviation of variability in EVRA between two experienced observers was 9.7TV regurgitation was improved in all patients. Using echocardiography, the early post-operative grade of residual regurgitation through the reconstructed valve apparatus was recorded as mild or moderate in all patients.No patients in this cohort (> 12 years of age) underwent bidirectional cavopulmonary anastomosis.Four of the 20 patients experienced early, para-valve surgical break down of the cone reconstruction, all within 30 days of surgery. These tended to occur more during earlier years of the 2009–2018 surgical program, but with no measureable significant clustering. The serial surgical case number and year of surgery for each of these four patients was case 6 (2010), case 10 (2013), case 14 (2014), case 16 (2014). One of these four patients subsequently died, 6 days post-operatively, with right heart failure and multi-organ dysfunction.The mechanism of repair breakdown in each patient was tension and subsequent dehiscence caused by detachment of the septal margin of the surgical repair, leaving the cone-valve apparatus intact, but allowing a significant “paravalvar” leak. In one patient the posterior commissuroplasty sutures dehisced, and was subsequently repaired with a bovine pericardial patch. In two other patients the septal component of the cone repair dehisced. One of these patients has undergone re-repair, with bovine pericardial patch to repair the dehisced section. All patients undergoing re-repair subsequently had an uneventful recovery. No patient has undergone TV replacement.p = 0.01).Table p = 0.04).The pre-operative functional RV volume (RVEDVi) was smaller in those patients with breakdown of surgical repair, (median 132 mL/m2 (83–168) vs 177 mL/m2 (101–353), o (60–78) vs 50 o (20–71), p = 0.01). This is illustrated in the scatterplot, Fig. o, the relative risk of dehiscence was 3.2 .Associated with this, and simpler to measure, the Ebstein valve rotational angle (EVRA) was significantly greater in the 4 patients suffering surgical dehiscence  predicted surgical outcome in our cohort.For most patients, the EVRA correlates loosely with a Carpentier-type classification, but the EVRA is a more pragmatic, quantitative parameter, easily measureable in every patient.We suggest that measuring this angle may help to identify those Ebstein valves with less abundant leaflet tissue that is available for the cone reconstruction. The EVRA may indicate those cases where the tension in the reconstruction will be greater, and thus greater risk of surgical breakdown. The surgical strategy for those patients with a greater EVRA is highly likely to require augmentation of leaflet tissue to complete the valve repair.As described previously  a partiaOf note, since identification of these dehiscence cases in our centre, the surgical technique has been recently modified. Pledgeted sutures are now routinely used in the posterior commissural area, and the septal components of the cone valve are augmented with pericardial tissue and extended to minimize tension, if judged necessary.Greater rotation of the valve, with a larger EVRA, also correlated with a more tethered, fibrosed and thickened anterior valve leaflet. The variations and number of anterior leaflet attachments and fenestrations were not independently quantified in our study, but these issues are also a crucial aspect of the technical challenge for effective valve reconstruction, and could be quantified with detailed imaging.The pre-operative functional RV end-diastolic volume was lower in the patients in whom cone reconstruction broke down early after surgery. Thus, a salient finding in our study is that the specific prognosis of surgical cone reconstruction does not necessarily align with the conventional clinical severity indices that may give natural prognosis of native Ebstein anomaly –11.The EVRA was measureable in all patients, with reasonable reproducibility of the measurement. The difference between observers was greatest when angle measurements were at the lower range, which is less critical if using this angle as a surgical decision tool.Limitations: Despite the clear findings, we acknowledge that the study methods have some limitations, inherent in any retrospective clinical analysis.Although standardized surgical methodology was used, there is possible confounding due to an era effect, and evolution over time of the surgeon’s skill, experience and technique.This study is not an analysis of disease severity with regard to surgical outcome, nor is it a study of the clinical selection criteria for surgical intervention. This study specifically assessed the effect of easily-measured CMR morphologic features on the early surgical outcome of cone reconstruction. Although there may have been subtle learning over time regarding case selection for surgery, the selection criteria for referring each patient for surgical intervention were not the focus of this investigation. In our Unit, patients were selected for surgery based on consensus among clinicians at multidisciplinary meetings, with the use of subjective and objective data involving CMR, echocardiography, exercise testing, and clinical symptoms.For Ebstein patients selected for surgical repair, comprehensive CMR assessment can characterize the valve and ventricles prior to cone reconstruction. Pragmatic observation of larger EVRA, smaller functional RVEDVi and leaflet edge thickening suggest risk of repair tension and dehiscence, and may demand specific modification of cone reconstruction technique. A larger EVRA may indicate need for leaflet augmentation.Although prospective testing is now needed, we suggest that this assessment process could help to improve case-selection, guide surgical methodology and therefore help to optimise cone surgical outcome for this complex group of patients.Additional file 1:Method of Ebstein valve rotation angle Patient 1 (EVRA 45 degrees). (MOV 6755 kb)Additional file 2:Method of Ebstein valve rotation angle Patient 2 (EVRA 50 degrees). (MOV 4189 kb)Additional file 3:Method of Ebstein valve rotation angle Patient 3 (EVRA 58 degrees). (MOV 6792 kb)Additional file 4:Method of Ebstein valve rotation angle Patient 1 (EVRA 78 degrees). (MOV 6323 kb)The four Additional files are movies corresponding to the image panels in Fig. 1. The movies illustrate the method of EVRA measurement using the end-systolic frame from CMR bSSFP cine images in four different patients from this cohort. In each file, the left-hand image is the RV long axis view, from which the EVRA is calculated. The EVRA is shown with green angle lines, in the end-systolic frame.The right-hand image in each panel is the 4-chamber view from the same patient. The green triple-line demonstrates the position of the RV long axis view relative to the 4-chamber view; a perpendicular plane through the centre of the right AV junction, parallel to the interventricular septum.


When one views a square-wave grating and dichoptically changes the average luminance or contrast of the monocular images, at least three perceptual phenomena might occur. These are the Venetian blind effect, or a perceived rotation of the bars around individual vertical axes; binocular luster, or a perceived shimmering; and binocular rivalry, or an alternating perception between the views of the two eyes. Perception of luster and rivalry occur when the "light bars" in the grating dichoptically straddle the background luminance (one eye’s image has a higher luminance than the background and the other eye’s image has a lower luminance than the background), with little impact from the "dark bars." Perception of rotation, on the other hand, is related to average luminance or contrast disparity, independent of whether or not the "light bars" straddle the background luminance. The patterns for perceived rotation versus binocular luster and binocular rivalry suggest at least two separate mechanisms in the visual system for processing luminance and contrast information over and above their differing physiological states suggested by their different appearances. While luster and rivalry depend directly on the relation between stimuli and the background, perceived rotation depends on the magnitude of the luminance or contrast disparity, as described by the generalized difference model. Binocular vision allows us to detect differences between the two eyes' views, extracting information from binocular disparities.  while oIt is clear that the visual system responds to luminance and contrast information with multiple perceptions, including brightness and perceived contrast . OuWe demonstrate that the Venetian blind effect, binocular luster, and binocular rivalry can be perceived in the same square-wave grating by manipulating luminance or contrast disparity . The key stimulus feature for perceiving luster and rivalry is the relation between each monocular grating image and the background luminance. Given a minimum amount of luminance or contrast disparity, a perception of luster occurs when luminance values of the monocular images "straddle" the background luminance (one eye’s image has a higher luminance than the background and the other eye’s image has a lower luminance than the background). Rivalry follows as the luminance disparity increases. Perceived rotation, or the Venetian blind effect, can be described with reference to the average luminance and contrast disparity of the viewed gratings, ignoring whether or not the monocular images straddle the background luminance. We argue that the three visual phenomena must be controlled by at least two underlying mechanisms for processing binocular luminance and contrast information: one supporting the perception of rotation and the other that of luster and/or rivalry. Again, the latter mechanism must involve more than one physiological state as the perceptual qualities of luster and rivalry differ. Our results cannot be explained by other processing mechanisms, e.g., the processing of geometric disparity that is also known to induce binocular rivalry.The Venetian blind effect, or perceived rotation engendered by a luminance disparity or contrast disparity, was modeled by Cibis and Haber  as a geoA separate irradiation model was developed by Filley et al.  based diThe Cibis-Haber model predicts that the Venetian blind effect will not be visible at moderate contrasts since the region between the light bars of a given square-wave grating will be above retinal illuminance threshold. Both the Cibis-Haber and the von Helmholtz-inspired irradiation models predict that perceived rotation will vary with edge blur width since the apparent location of a blurred edge varies with the blur width . Dobias and Stine ) Participants performed practice sessions until they felt comfortable and responses stabilized. For Experiments I and II, these were: for JJD, 2 and 2 sessions; for RSH, 1 and 3 sessions; for WWS, 2 and 2 sessions, respectively. They then performed formal sessions until 12 trials were completed for every condition in that experiment. Because of varying numbers of conditions, this meant 3 total sessions in Experiment I and 6 in Experiment II.The data were plotted as the probability of responding "present" to each perceptual phenomenon across the 12 trials for each condition, using standard error bars based on the score estimator  see als some of We performed Experiment I to measure the range of average luminance and contrast disparities over which perceived rotation, luster, and rivalry would be reported. Rotation should be reported over a wide range of disparities with lower and upper bounds , 7 and , given tThe onset of luster should be associated with that disparity where the luminance of the stimulus bars either straddles the luminance of the background  or, perh2 where the light and dark bars averaged 42.5 cd/m2 (the base luminance) and had a contrast of 0.5 (the base contrast). eft or (r)ight. Leye can be calculated usingr, subtracting modulation instead of adding. We abbreviate this as2.Experiment I used square-wave gratings made up of three light bars and four dark bars at a spatial frequency of 1.5 cycles per degree akin to . Each mon, after . Dichoptontrast ,There were three independent variables: whether dichoptic luminance modulation or dichoptic contrast modulation were presented, the amount of the modulation, and whether the left or right eye received the image with higher luminance or contrast. Possible modulation values for either luminance or contrast varied in 0.10 increments from 0.10 to 0.90 see  Tables, Data are shown in For all three subjects, thresholds (modulation engendering a 0.5 probability of response) for rotation were below those for luster, which, in turn, were below those for rivalry when viewing luminance modulations. Neither luster nor rivalry was seen with contrast modulations, though rotation was perceived. Finally, for two of three subjects, a drop in rotation was perceived at modulations approaching 0.9.JJD may have exhibited some evidence of a stronger input from the left eye for perceived rotation with a luminance disparity and for the right with a contrast disparity. RSH showed a stronger input from the left eye for luminance disparities and, perhaps, for contrast disparities. WWS showed, perhaps, a stronger input for perceived rotation from the left eye for both luminance and contrast disparities.Participants reported informally that all rivalry with these images was mosaic. Further, sustained luster was reported for lower to moderate luminance disparities while transient luster was reported for higher disparities.All three subjects exhibited different thresholds for perceived rotation, luster, and rivalry with luminance disparities, demonstrating differing onsets for the three perceptions and that all three may be seen simultaneously. However, only perceived rotation was evident with contrast disparities, suggesting that the mechanisms underlying perceived rotation, or the Venetian blind effect, are distinct from those underlying luster and rivalry.Interocular differences in the strength of input to perceived rotation replicated that reported for RSH and WWS by Hetley and Stine . FinallyOur results suggest that the luminance of the bright bars must straddle the background luminance before luster and rivalry reach threshold. Further, only the light bars control this threshold. Anstis , Fry andluminance source, which is described further in the section on stimuli, below.We performed Experiment II to measure the effects of individual bar luminance on perceived rotation, luster, and rivalry while holding the luminance surrounding the bars constant. The bar luminance values were taken from Experiment I stimuli. Specifically, our stimuli used bright bars with luminance that matched either (1) the average luminance of the monoptic stimuli from Experiment I with average luminance disparities, (2) the luminance of the bright bars of the monoptic stimuli from Experiment I with average luminance disparities, (3) the luminance of the bright bars of the monoptic stimuli from Experiment I with contrast disparities, (4) the luminance of the dark bars of the monoptic stimuli from Experiment I with contrast and average luminance disparities (dark bars covered the same luminance range regardless of which type of disparity was used). We call the independent variable composed of these four conditions the We manipulated the luminance of the bars to vary exactly as they had varied in Experiment I, creating what we term "Experiment I equivalent disparity modulation." When coupled with the constant background luminance, both contrast and average luminance vary in each monoptic image with Experiment I equivalent disparity modulation . This manipulation allowed us simultaneously to test a prediction from Hetley and Stine  concernimax(L) is the maximum possible response to a grating with average luminance L. For Eq  Cn+σ50n+MwhereRm3 ofeye and Leye are the contrast and average luminance of the square-wave grating viewed by eye, gain is a multiplicative gain constant, and MES is a constant that describes when a disparity becomes so large one eye’s image suppresses the other eye’s image, effectively giving an edge shift of zero. . In Backus, Banks, van Ee, and Crowell [Generalizing the work of Hetley and Stine , Dobias  Crowell , the HSR Crowell , Equatio Crowell , EquatioThe generalized intensity difference model should describe variations in the probability of perceiving rotation as a function of Experiment I equivalent disparity with a single set of parameters across all conditions. However, only those instances where the luminance of the bright bars straddle the background, or nearly straddle the background, should create the perception of luster, with rivalry appearing as the luminance disparity increases.2 uniform field , and one for "dark bars." Note that the neutral condition for "average luminance" is a screen that is blank gray except for alignment lines, and so even though this condition was presented, it will not be plotted in this experiment. Each combination of values, including the neutral conditions, appeared twice in one session. Participants performed six sessions, therefore completing 12 trials for each condition.Data are shown in The "light luminance bars" and "light contrast bars" plots exhibit well-defined thresholds for the initial perception of binocular rivalry (riv) and binocular luster (lstr) that mirror those in Experiment I. The threshold for rivalry was above that for luster, both could be seen at one time, and, with the possible exception of RSH seeing luster , both weJJD and RSH showed clear threshold disparities for rotation, or the Venetian blind effect (Vb), in the light bar contrast and dark bar conditions . FurtherOur subjects showed little effect of the eye viewing the more-intense stimulus. Participants again noted, informally, that these images only underwent mosaic rivalry maxL = 1, σ50 = 0.15, n = 2.4, nL = 3.0, M = 8.22, ML = 0.0, and gain = 1.0) with the exception of MES. Perceived horizontal size ratios were then calculated for each Experiment I equivalent disparity presented across the four conditions. The Mathematica 11 Interpolation module was used to build a spline interpolation to generate a continuous predicted perceived horizontal size ratio function from the model. Using a hierarchical approach, that function was passed through a Laplace cumulative distribution function in order to generate probabilities for reporting perceived rotation. MES from Eq . Then, using MES = 7.79, shift = -0.096 from the joint least-squares fit, the spread, β, parameter was fit individually for JJD, RSH, and WWS across the "light luminance bars," "light contrast bars," and "dark bars" conditions. Our reasoning was that the spread of the psychometric functions would be expected to vary across subjects while, according to our model, the remaining three parameters would be specific to the particular experimental context, and thus common across the three subjects.The probability of perceiving rotation, or the Venetian blind effect, showed both lower and upper threshold luminance disparities. In order to generate specific descriptions from the generalized difference model, we fixed the values for all of the constants to those used in Hetley and Stine , RSH (R2 = 0.762), and WWS (R2 = 0.722). Of the 78 probabilities represented in each figure, the percentages of those with 95% confidence intervals that include the model prediction are 90% of the intervals for JJD, 79% of the intervals for RSH, and 64% of the intervals for WWS.The plots in R2 vice versa . The. TheviceThat the appearance of luster and rivalry radically differ and that the threshold for rivalry is consistently higher than that for luster, of course, implies that the overlap between luster and rivalry is not complete; they involve distinct physiological states.Perceived rotation, or the Venetian blind effect, followed generalized difference model predictions.Our results, together with those of Hetley and Stine , expand By constraining images to vary only in luminance or contrast, we are able to compare phenomena without interference by other perceptual processing, e.g., processing of geometric disparity to induce binocular rivalry. Experiments I and II demonstrate that luster and rivalry also vary with the interocular difference in average luminance or contrast. However, that luster and rivalry are tied to straddling the background luminance Click here for additional data file.S2 TableListed is the luminance contrast viewed by each eye for the modulations used in Experiment I when the left eye’s image had the higher contrast.(PDF)Click here for additional data file.S3 TableListed is the luminance of the individual bars viewed by each eye for the avg modulation used in experiment II when the left eye’s image had the higher luminance bar.(PDF)Click here for additional data file.S4 TableListed is the luminance of the individual bars viewed by each eye for the llm modulation used in experiment II when the left eye’s image had the higher luminance bar.(PDF)Click here for additional data file.S5 TableListed is the luminance of the individual bars viewed by each eye for the lcn modulation used in experiment II when the left eye’s image had the higher luminance bar.(PDF)Click here for additional data file.S6 TableListed is the luminance of the individual bars viewed by each eye for the dar modulation used in experiment II when the left eye’s image had the higher luminance bar.(PDF)Click here for additional data file.


Also, LV volumes, mass and septal wall thickness decreased in both, but to a larger extent in AVS than in HOCM patients. AVR improved wall thickening (p < 0.05) and did not change systolic strain rate. Myectomy did not affect wall thickening and reduced septal systolic strain rate (p = 0.03). Both AVR and myectomy induced positive structural remodeling in line with a reduction of pressure overload. A concomitant recovery in systolic function however was found in AVR only. The systolic functional deterioration in HOCM patients seems to be inherent to myectomy and the ongoing and irreversible disease.Surgical therapies in aortic valve stenosis (AVS) and hypertrophic obstructive cardiomyopathy (HOCM) aim to relief intraventricular pressure overload and improve clinical outcome. It is currently unknown to what extent myocardial adaptation concurs with restoration of intraventricular pressures, and whether this is similar in both patient groups. The aim of this study was to investigate changes in myocardial adaptation after surgical therapies for AVS and HOCM. Ten AVS and ten HOCM patients were enrolled and underwent cardiac magnetic resonance cine imaging and myocardial tagging prior to, and 4 months after aortic valve replacement (AVR) and septal myectomy, respectively. Global left ventricular (LV) analyses were derived from cine images. Circumferential strain was assessed from myocardial tagging images at the septal and lateral wall of the mid ventricle. Pressure gradients significantly decreased in both AVS and HOCM after surgery (The online version of this article (10.1007/s10554-019-01563-3) contains supplementary material, which is available to authorized users. Left ventricular hypertrophy (LVH) is a common finding in clinical practice and is associated with morbidity and mortality. LVH can be detected in acquired and genetic cardiac diseases. The most common cause for acquired LVH is in aortic valve stenosis (AVS). In response to systolic pressure overload, the myocardium hypertrophies in an attempt to normalize increased wall stress . PatientThe study protocol was in agreement with the principles outlined in the Declaration of Helsinki and was approved by the Medical Ethics Review committees of the participating hospitals . All participants gave written informed consent prior to inclusion.2, according to the American Society of Echocardiographic guidelines [−1. To compare myocardial function in AVS and HOCM patients before surgical therapy, 14 gender-matched healthy subjects were included as a control group.Ten AVS patients eligible for AVR therapy and ten HOCM patients eligible for septal myectomy, were prospectively enrolled in the study between October 2011 and November 2015, as described previously . Inclusiidelines , 17. TheAll AVS and HOCM participants underwent a CMR scan, 2 weeks prior to, and 4 months after surgery. CMR was performed on a 1.5 Tesla whole body scanner , using a six-channel phased-array body coil. In all patients and controls, cine images were obtained using a breath-hold segmented k-space balanced steady-state free precession (bSSFP) employing retrospective electrocardiographic gating, with contiguous short axis slices to cover the whole ventricle from base to apex. Ventricular volumes at end-diastole and end-systole, and mass were obtained from the cine short axis images. Left atrial (LA) volumes and emptying fraction (LAEF) were obtained from a stack of transversely oriented slices on a two-chamber view at the level of the lower leading edge of the mitral valve annulus to cover the left atrium . A multiThe cine images were analyzed off-line by a single investigator, using MASS analysis software . Endocardial contours were drawn at end-diastole and end-systole to calculate LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LVEF. Addition of epicardial contours was used to calculate LV mass and wall thickening. Tissue tagging images were analyzed by Intag  softwareStatistical analysis was performed using SPSS software . All variables were visually checked for normal distribution by appreciation of the histogram with separate needs of the patient groups. All data were not normally distributed and presented by median with interquartile range and was compared to healthy controls with a Mann-Whitney-U test. Measurements prior to, and after surgical therapy were compared within groups using Wilcoxon signed-rank test. Exact Chi square test was used for categorical variables. As three separate statistical tests were performed for each outcome measure in each group of patients (comparison of pre- and post-measurement and separate comparison of pre- and post- measurements to the control group) we used a two-sided significance level of 0.05/3 to account for multiple testing.p < 0.001). Except for LV mass, all global LV dimensions were comparable to controls (Table p < 0.001), whereas only septal circumferential strain was significantly reduced (Table p = 0.013). Septal systolic strain rate was reduced compared with controls . Lateral systolic and diastolic strain rates before AVR were similar to controls . Pressure gradients were significantly higher in HOCM with a concomitant higher LA volume, as listed in Tables p < 0.001). Septal wall thickening and septal circumferential strain were significantly reduced compared with controls (Table p < 0.01). Similar to AVS patients, septal systolic and diastolic strain rate were reduced compared with controls before myectomy . Lateral systolic and diastolic strain rate were comparable to controls (Table p = 0.53). Global longitudinal strain was significantly affected compared with controls . Global LV dimensions and LA volume decreased after AVR, however there was no significant change in LVEF and LAEF (Table p = 0.4) and regional circumferential strain did not significantly improve after surgery .Both peak and mean transvalvular pressure gradients in AVS patients significantly decreased after surgery . As was to be expected, septal EDWT decreased following myectomy. Also, LV mass and LA dimension decreased after myectomy, but without a change in LV dimensions, LVEF or LAEF (Table p = 0.52). With respect to regional circumferential strain only septal circumferential strain further deteriorated with worsening of septal systolic strain rate (Table p = 0.043), while peak VO2 remained similar .From a total of ten HOCM patients, one patient declined follow up CMR, and another patient underwent pacemaker implantation due to an atrioventricular block. Measurements at baseline were included from ten patients, and at follow-up from the remaining eight patients. Both LVOT peak and mean gradients improved after septal myectomy , suggesting lowering of diastolic filling pressures. Wall thickening improved after AVR, albeit without improvement in strain and strain rates. Similar to AVS patients, strain rates of the lateral wall were not affected after surgery for HOCM, while septal systolic circumferential strain rate further deteriorated, probably as a consequence of the myectomy. Both AVS and HOCM patients showed a reduction in LV wall thickness and mass after surgery, though this effect was more pronounced in AVS patients  only AVS patients showed functional improvement after surgical treatment, evident from improved global wall thickening but unaffected strain rates, whereas HOCM patients deteriorated with respect to septal wall thickening and systolic strain rate.This study provided the unique opportunity to prospectively investigate myocardial function in patients with two different etiologies in LVH, and to what extent reverse remodeling occurs in AVS and HOCM patients after surgical treatment, AVR and septal myectomy respectively. The main findings of the present study are that (1) both AVS and HOCM patients have significantly higher LV mass and LA volumes than controls, and in HOCM smaller LV volumes compared with AVS patients and controls; (2) both patient groups had lower septal wall thickening and systolic strain rates than controls; (3) both patient groups demonstrated reversed In both patient groups, intraventricular pressure gradients improved after surgery with a concomitant reduced LA volume, probably reflecting improved diastolic pressures. AVR is known to improve symptoms, reduce LV mass and wall thickness , 25, whiWhereas the increased pressure gradient in AVS is a static phenomenon, the pressure gradient in HOCM is of a dynamic nature, mainly depending on loading conditions . Septal Diastolic dysfunction is a hallmark of HOCM, and seems to be largely caused by increased interstitial fibrosis leading to reduced LV compliance . The redThe present study demonstrates reversed structural remodeling in both AVS and HOCM patients after surgery, however, recovery in systolic function was only seen in AVS. Furthermore, HOCM patients demonstrated systolic functional deterioration which seems to be inherent to septal myectomy and the ongoing and irreversible cardiac pathophysiology. Although septal myectomy reduces the risk of sudden cardiac death, this study emphasizes the need for future research in therapies to enhance myocardial recovery.However, there are several limitation in this study. Several medical centers were involved in the inclusion of patients for advanced imaging before and after cardiac surgery, and therefore, the included patients do not reflect the actual number of patients who yearly undergo cardiac surgery. As the number of participants included were limited, the conclusions should be interpreted carefully. Yet, even with this relative small study population we were able to demonstrate differences in myocardial adaptation after surgery for AVS and HOCM. Although tissue tagging is a novel and accurate method to assess myocardial function, tagline fading in end-diastole occurred in two patients who were therefore excluded from the diastolic strain rate analysis. Accurate detection of diffuse fibrosis using T1 mapping might have increased our understanding of the absence of functional recovery in HOCM. Furthermore, evaluation by CMR was performed at 4 months after surgery which seems reasonable but not necessarily the optimal timing to capture full remodeling and functional recovery.Below is the link to the electronic supplementary material.Supplementary material 1 (DOCX 448 KB)


A 61-year-old male, with a history of emphysema, obstructive sleep apnea, and hypertension, presented to the emergency room with worsening shortness of breath over a three-month period. The patient also complained of orthopnea, paroxysmal nocturnal dyspnea, and progressively worsening lower limb swelling. On examination, the patient had jugular venous distension, bilateral lower extremity edema, and bibasilar crackles. The laboratory evaluation showed an elevated B-natriuretic peptide level and a normal troponin level. A transthoracic echocardiogram (TTE) showed a reduced left ventricular ejection fraction (LVEF) of 20%-25% with prominent hyper-trabeculations noted in the left ventricle, most prominent in the lateral and apical walls. These findings were concerning for left ventricular non-compaction (LVNC). The patient underwent left heart catheterization, which did not show obstructive coronary disease as a cause of his cardiomyopathy. The patient was managed with guideline-directed therapy for heart failure and was started on warfarin due to the increased risk of thromboembolism associated with LVNC. During his admission, he exhibited multiple episodes of nonsustained ventricular tachycardia and was subsequently evaluated by electrophysiology (EP). He was discharged home with a wearable cardioverter defibrillator with instructions to follow up with EP in three months for an evaluation of implantable cardioverter-defibrillator (ICD) placement for primary prevention. Left ventricular non-compaction (LVNC) is a rare cardiomyopathy that is being diagnosed with increasing frequency as awareness of the disorder spreads and diagnostic modalities advance. The etiology is thought to occur in utero, as physiologic sinusoids fail to fully compact into mature myocardium . The resA 61-year-old male, with a history of emphysema, obstructive sleep apnea, and hypertension, presented to the emergency room with worsening shortness of breath over a three-month period. The patient also complained of orthopnea, paroxysmal nocturnal dyspnea, and progressively worsening lower limb edema. On examination, the patient had jugular venous distension, bilateral lower extremity edema, and bibasilar crackles. The laboratory evaluation showed a B-natriuretic peptide level of 11,065 pg/ml and a troponin level of < 0.04 ng/ml. A transthoracic echocardiogram showed a reduced left ventricular ejection fraction (LVEF) of 20%-25% with prominent hyper-trabeculations noted in the left ventricle, most prominent in the lateral and apical walls. These findings were concerning for LVNC. Cardiac magnetic resonance imaging (CMRI) showed a non-compacted to compacted myocardium ratio of 5:1 at the left ventricular apex (Figure LVNC is a rare cardiac condition characterized by excessively prominent left ventricular trabeculae and deep intertrabecular recesses, with continuity between the left ventricular cavity and these recesses. Isolated LVNC occurs in the absence of other congenital abnormalities. Typically, the left ventricle is involved, although the involvement of the right ventricle has also been described . It is bThe systolic dysfunction in LVNC is thought to occur due to a relative ischemia of the myocardium with a mismatch of myocardial oxygen supply and demand. The multiple prominent trabeculations cause a restriction in filling, an abnormal ventricular relaxation pattern and diastolic dysfunction, with a generally poor eventual outcome for patients . Two uniIn conclusion, LVNC is a diagnosis that should be considered for patients presenting with signs and symptoms of heart failure and abnormal structural findings on various cardiac imaging modalities. Although primarily diagnosed in childhood, identifying and diagnosing LVNC in adults has significant clinical implications. With early identification, potentially preventable complications, such as ventricular arrhythmias and thromboembolism, may be avoided. In addition, patients need to be started on appropriate therapeutic management for heart failure symptoms to prevent progression.


Myocardial native T1 and T2 mapping are promising techniques for quantitative assessment of diffuse myocardial pathologies; however, due to conflicting data regarding normal values, routine clinical implementation of this method is still challenging.To evaluate this situation during daily clinical practice the characteristics of normal values obtained in 60 healthy volunteers who underwent magnetic resonance imaging (MRI) scans on 1.5T and 3T scanners were studied. The T1 modified look-locker inversion recovery 3; modified for higher heart rates) and T2 navigator gated black-blood prepared gradient-spin-echo (GraSE) sequences were used.While age and body mass index did not affect relaxation times, a gender and heart rate dependency was found showing higher T1 and T2 values in females, whereas at higher heart rates a prolongation of T1 and a shortening of T2 relaxation times was found. Particularly prone to artifacts were T2 measurements at 3T and the inferolateral wall. In the individual setting mean relaxation times for T1 were 995.8 ± 30.9 ms at 1.5T and 1183.8 ± 37.5 ms at 3T and 55.8 ± 2.8 ms at 1.5T and 51.6 ± 3 ms at 3T for T2 indicating a high dependency of reference values on MRI protocol when compared to the literature. Furthermore, as presumed mean T1 and T2 values correlated in the same individual.The T1 and T2 relaxation times depend on physiological factors and especially on MRI protocols. Therefore, reference values should be validated individually in every radiological institution before implementing mapping protocols in daily clinical practice. Correlation of mean T1 and T2 values in the same proband at both field strengths indicates intraindividual reproducibility. Cardiac magnetic resonance imaging (CMRI) is the gold standard in noninvasive myocardial tissue characterization ; howeverThe T2-weighted (T2w) CMRI and T2-weighted short tau inversion recovery (STIR) techniques are well-established sequences for the detection of myocardial edema  to diffeAn important aspect of mapping techniques is that the obtained information has prognostic relevance. The pathology cannot only be detected but also be quantified and the course of disease can be monitored under treatment. Therefore, mapping techniques have the potential to act as biomarkers to facilitate diagnostic decision making  .Despite promising results in the literature, routine implementation of this technique remains challenging. This might be associated with conflicting data regarding normal values. Recent publications suggest that even in sophisticated facilities, a variety of technical, image acquisition and patient-dependent factors influence T1 and T2 relaxation times . To evalThe study protocol was approved by the local ethics committee of the province of Salzburg (Number 415-EP/73/412-2014). The cohort consisted of 60 healthy volunteers (33 women/27 men), stratified into two equally sized age groups <45 and ≥45 years of age  and right ventricular (RV) wall motion, normal LV and RV ejection fraction as well as normal LV and RV mass were confirmed by the evaluation of CMRI-cine sequences.Exclusion criteria were general contraindications for MRI , pregnancy, consumption of alcohol prior to the examination, known systemic disease and hardness of hearing.The CMRI procedure was performed using both a commercially available 1.5T and 3T scanner . All volunteers were consecutively examined on two MRI scanners (1.5T and 3T) in a supine position. A combined 16-channel anterior/posterior coil system was used for the 1.5T scanner, a 6-channel cardiac RF coil and MultiTransmit technology was used for the 3T scanner. At 3T, in addition to B0 shimming, after B1 calibration RF shimming was applied for better field uniformity. Electrocardiography (ECG) was used for cardiac gating.All studies were performed by experienced radiographers who were trained in the study protocol.2, matrix = 176 × 133, slice thickness = 8 mm, SENSE factor = 2 and cardiac phases = 30. Imaging parameters for 3T were: TR = 2.8 ms, TE = 1.4 ms, FA = 45°, FOV = 320 × 350 mm2, matrix = 176 × 208, slice thickness = 8 mm, SENSE factor = 2 and cardiac phases = 24.Balanced steady-state free-precession (bSSFP) cine images were obtained in the 4‑chamber view and in a stack of short axes (SAX) covering the ventricles. Wall motion was assessed and the LV ejection fraction was quantified. Imaging parameters for 1.5T were: repetition time (TR) = 2.8 ms, echo time (TE) = 1.38 ms, flip angle (FA) = 60°, field of view (FOV) = 350 × 286 mm2, voxel size 2 × 2 × 10 mm3 and SENSE factor = 2. The MOLLI schema used was 5 beats (3s) 3 beats. Imaging parameters for 3T were: TR = 2.6 ms, TE = 1.3 ms, FA = 35°, FOV = 380 × 356 mm2, voxel size 2 × 2 × 10 mm3 and SENSE factor = 2. The MOLLI schema used was 5 beats (3s) 3 beats.Data for T1 mapping were acquired in three SAX slices . The balanced SSFP-based modified look-locker inversion recovery (MOLLI) technique was used . Imaging2, voxel size: 2 × 2 × 10 mm3 and SENSE factor = 2. The imaging parameters for 3T were: TR = 1 heartbeat, 9 echos TE1 = 11 ms, ∆TE = 5.7 ms, FA = 90°, EPI factor: 3, voxel size: 2 × 2 × 10 mm3 and SENSE factor = 2.Data for T2 mapping were acquired in three SAX planes . A navigator gated black blood prepared gradient spin-echo sequence (GraSE) was used  and 9 imUsing Philips software  the bSSFP cine images in SAX and 4CH were evaluated for wall motion abnormalities. The LV and RV ejection fraction were determined by manually contouring the endocardial borders in end-diastolic and end-systolic cardiac phase in SAX. The LV and RV mass, as well as the body surface indexed mass were determined by manually contouring of the endocardial and epicardial borders of both ventricles.All source images were assessed visually regarding artifacts caused by cardiac or respiratory motion or susceptibility. Artifacts were specified as focal, diffuse or band-shaped signal abnormalities of the myocardium (bright/white or dark/black) and led to exclusion of the affected segment. Some myocardial segments had to be excluded due to misplacement of the stack. Examples of artifacts that led to segment exclusions are illustrated in Fig. www.medis.nl) was used for generating the maps, segmentation and segmental quantification. The maps were generated by defining a region of interest (ROI) in the mid-ventricular septum. The endocardial and epicardial contours were manually drawn. To avert disturbances from the blood pool, 10% of the subendocardial and subepicardial aspect of the ROI were excluded automatically , 95% confidence intervals (CI), Pearson’s correlation coefficient and 1‑factorial ANOVA model together with two-sided, independent t‑tests were used to evaluate data. Normal ranges were estimated by using 2.5% and 97.5% percentiles to end up with 95% CI for the empirical distributions. Regression analysis was used to compare values between 1.5T and 3T. A STICA 13  and wereAll 120 CMRI scans were carried out without adverse events. The scan was incomplete in one subject due to technical problems and two subjects had to be excluded due to the detection of a chronic disease . Therefore, 115 examinations in 58 subjects were available for further analysis. The T1 and T2 maps at 1.5T were available for 57 subjects, T1 and T2 maps at 3T were available for 58 subjects. Due to malpositioning of the basal slice too close to the atrioventricular plane 15 segments (1.6%) had to be eliminated from the T1 measurements at 1.5T, 10 segments (1.1%) from T1 at 3T, 15 segments (1.6%) from T2 at 1.5T and 21 segments (2.3%) from T2 at 3T measurements. Females and males showed no statistically significant differences with respect to age, heart rate and body mass index . Particularly prone to artifacts was segment 16 . At 3T a total of 918 segments were available, of which 104 segments were excluded due to artifacts (11.3%). The inferolateral wall in the apical and mid-ventricular slices  was especially prone to artifacts  and heart rate. No statistically significant differences in different age groups or in volunteers with a BMI above 25 kg/mnd Table .Table 3DGender-specific and heart rate-specific global values are presented in Table p = 0.057), at 3T significant differences were detectable between the base and the apical slice (p = 0.013) and furthermore between the midventricular and the apical slice (p = 0.002).The next step was focused on slice and segment-specific differences using a 16-segment model of the heart. Table p < 0.001) showing higher values in the septal and inferior segments and lower values in lateral segments  could be confirmed . At 3T 131 segments out of 907 segments were excluded due to artifacts (14.4%). The majority of excluded segments were in the basal slice, especially in the inferior and the lateral wall , basal and apical slices (p < 0.001) and moreover between middle and apical slices (p < 0.001) were present. Moreover, significant differences between T2 values at 3T of basal and apical slices (p < 0.001) and middle and apical slices (p < 0.001) were evident. Gender-specific values of T2 relaxation times are presented in a 16-segment model of the heart   of global T2 relaxation times by 2.0 ms was revealed at 3T in the subgroup of volunteers with a heart rate of ≥70 bpm. At 1.5T the reduction of T2 relaxation times was not significant (Table Heart rate seemed to have an effect on T2 relaxation times. A significant reduction (p = 0.002)  Fig. b.This study was designed to establish reference values for T1 and T2 relaxation times in healthy volunteers for our specific setting at 1.5T and 3T. Furthermore, the correlation between the intra-individual global T1 and T2 values at different field strengths was studied and published data concerning possible influences of physiological factors on relaxation times were reproduced.As already pointed out in previous publications, different mapping techniques and field strengths are associated with a variety of normal values . These vApart from differences in study protocols patient-related physiological factors are also presumed to affect relaxation times. Of note, various studies found an association between aging and lower T1 and higher T2 relaxation times , 21, 25.In this cohort, gender was a confounding factor for T1 and T2 relaxation times at 1.5T and 3T. According to previous studies, females showed a significant prolongation of T1 relaxation times at 1.5T and 3T and of T2 relaxation times at 1.5T , 26–28; The prolongation of T1 relaxation times in higher heart rates is in accordance with Piechnik et al.  while otWhile a correlation of relaxation times at different field strengths in the same individual is presumed, to the best of our knowledge no study thus far has investigated this issue in a larger cohort. Therefore, we focused on this interesting subject and indeed were able to verify this association. This means that if a subject had low mean T1 values at 1.5T, these values were also low at 3T. As there are limited data on the reproducibility of myocardial T1 and T2 relaxation times at different field strengths in the same individual this is an important finding. The correlation was higher for T1 than for T2 values Fig. . This miAs already noted by other authors, also in zjis cohort the intrasubject and intersubject variability of T1 and especially of T2 values was considerably high per slice and per segment , 21, 38,, 6 and 7Due to respiratory or cardiac motion artifacts and susceptibility artifacts, a proportion of segments had to be excluded from this analysis Fig. . Of noteIn this study the topics of extracellular volume (ECV) and post-contrast T1-mapping were not elaborated, as it was pointed out in previous studies that native T1-mapping could differentiate between healthy and diseased myocardium with high sensitivity, specificity and diagnostic accuracy , 39. EveThere are several limitations to this study. This was a single center study of moderate sample size using MRI scanners from only one manufacturer. Therefore, a center-specific and manufacturer-specific bias cannot be excluded. No histological examination of the myocardium was performed. In the post-processing phase no program for motion correction was available which led to higher exclusion-rates of myocardial segments. Despite the relatively small size of the cohort results of studies using similar mapping techniques could be reproduced. This underlines the validity of these reference values and implications. As specified above, two thirds of the patients undergoing CMRI evaluation were below the age of 60 years. Therefore, this cohort consisted of younger volunteers, which might obscure a pre-described age dependency of relaxation times in the aged myocardium. These normal values can only be applied and generalized in younger patients in institutions using similar mapping techniques to ours.The results obtained during daily clinical practice in healthy volunteers indicated that T1 and T2 relaxation times showed gender and heart rate dependencies, even in T1 maps using a less heart rate sensitive MOLLI variant. Due to artifacts caution should be applied especially while performing T2 mapping at 3T and while measuring relaxation times in the inferolateral wall. As already pointed out in the consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI) , we also


Heparin-induced thrombocytopenia type II (HIT II) is a rare, immune-mediated complication of heparin therapy and can cause life-threatening thromboembolism. However, perioperative anticoagulation therapy for patients with a complication of HIT II has not been established.A 6-year-old boy with tetralogy of Fallot underwent radical intracardiac repair with administration of argatroban at 1 year old due to positive HIT antibody. Reoperation was scheduled for pulmonary valve insufficiency, using argatroban and nafamostat mesilate as anticoagulants. Argatroban has a long onset time and the activated coagulation time (ACT) requires 7–26 h to return to the preadministration level, making hemorrhage control difficult, while half-life of nafamostat mesilate is shorter than that of argatroban. Celite ACT reflects the effects of both argatroban and nafamostat mesilate, but kaolin ACT reflects only the effect of argatroban. Due to the early termination of argatroban administration based on Celite and kaolin ACTs, ACT recovered to ≤ 200 s at 5 h after the end of argatroban administration.Celite and kaolin ACTs can be used as markers to obtain close control of the required dose of argatroban in combination with nafamostat mesilate for the management of HIT II patients. Heparin-induced thrombocytopenia type II (HIT II) is a serious side effect caused by use of heparin . PeriopeThe patient was a 6-year-old boy of height 107.7 cm and weight 17.7 kg. He was born by scheduled Cesarean delivery after gestation of 38 weeks and 2 days, with weight 3026 g and height 45.5 cm, because his mother was after hysteromyctomy. At 1 day old, he was diagnosed with tetralogy of Fallot (TOF), and he received palliative surgery at another hospital at 6 weeks. At 1 year, more than 50% thrombocytopenia and upper extremity movement disorder appeared after catheterization, and he was diagnosed with HIT II because his functional assay was positive for HIT antibodies. Therefore, radical intracardiac repair with administration of argatroban was performed at the hospital. After this surgery, aortic regurgitation and residual defect of the ventricular septum were confirmed. Follow-up observation was performed for these symptoms, in addition to pulmonary stenosis and regurgitation, which were associated with TOF.Based on a desire for treatment at our hospital, the patient underwent a cardiac catheter test, which showed progression of pulmonary valve insufficiency. Thus, reoperation was scheduled for aortic valvuloplasty, pulmonary valve replacement, and repair of ventricular septal defect. Anesthesia was performed with slow induction of sevoflurane and maintained with fentanyl and sevoflurane/midazolam. No abnormalities were found on the coagulation test and HIT antibody had become negative, but argatroban and nafamostat mesilate were used as anticoagulants because some reports suggest that HIT II can redevelop due to heparin re-administration . During After thoracotomy, a 5-mg argatroban bolus was administered and continuous argatroban was started at 12 mg/h, which was then decreased to 3 mg/h because the activated partial thromboplastin time (APTT) was 136.6 s. However, since kaolin ACT decreased from 352 to 217 s, the dose was increased again to 12 mg/h and bolus administration of 2.5 mg was added. After kaolin ACT reached 501 s and the patient was placed on cardiopulmonary bypass, continuous administration of nafamostat mesilate was started at 50 mg/h, concomitantly with argatroban. ACT was continuously prolonged, and Celite ACT and kaolin ACT were 1500 and 600 s, respectively, at 3.5 h before weaning from cardiopulmonary bypass. Therefore, administration of argatroban was discontinued after the dose was decreased by half. ACT continued to be prolonged, although with some shortening, and thus the dose of nafamostat mesilate was decreased to 30 mg/h until weaning from cardiopulmonary bypass. Upon weaning, Celite ACT and kaolin ACT were 533 and 399 s, respectively.ACT decreased to ≤ 200 s (177 s) for the first time at 5 h and 1.5 h after discontinuation of argatroban and nafamostat mesilate, respectively. Operation and anesthesia times were 10 h 9 min and 11 h 36 min, respectively. Intraoperative hemorrhage was about 1000 ml, and 560 ml of red blood cells (RBCs), 520 ml of fresh frozen plasma (FFP), and 250 ml of platelet concentrate (PC) were transfused. There was no significant postoperative bleeding. Extubation was performed on the day after surgery and the patient was discharged on postoperative day 11.HIT II is a serious side effect of heparin that may cause thrombocytopenia and thromboembolism when platelet factor 4/heparin complex and HIT antibody form an immune complex to activate blood platelets . Re-admiArgatroban, a direct thrombin inhibitor that binds avidly and reversibly to the catalytic site of thrombin and that does not require other cofactors to exert its antithrombotic action, is often used in open-heart surgery for patients with HIT II , 10. Aft


Because hearts in acute myocardial infarction are often prone to ischemia-reperfusion damage during cardiac surgery, we investigated the influence of intracellular crystalloid cardioplegia solution (CCP) and extracellular blood cardioplegia solution (BCP) on cardiac function, metabolism, and infarct size in a rat heart model of myocardial infarction.Following euthanasia, the hearts of 50 rats were quickly excised, cannulated, and inserted into a blood-perfused isolated heart apparatus. A regional myocardial infarction was created in the infarction group (18 hearts) for 120 min; the control group (32 hearts) was not subjected to infarction. In each group, either Buckberg BCP or Bretschneider CCP was administered for an aortic clamping time of 90 min. Functional parameters were recorded during reperfusion: coronary blood flow, left ventricular developed pressure (LVDP) and contractility (dp/dt max). Infarct size was determined by planimetry. The results were compared between the groups using analysis of variance or parametric tests, as appropriate.p = 0.0062]; dp/dt max. 73 ± 11% vs. 23 ± 2.7% [p = 0.0001]), whereas coronary flow was similarly impaired . The infarct in BCP-treated hearts was smaller (25% of myocardium) and limited to the area of coronary artery ligation, whereas in CCP hearts the infarct was larger  and myocardial necrosis was distributed unevenly to the left ventricular wall.Cardiac function after acute myocardial infarction, 90 min of cardioplegic arrest, and 90 min of reperfusion was better preserved with Buckberg BCP than with Bretschneider CCP relative to baseline (BL) values (LVDP 54 ± 11% vs. 9 ± 2.9% [In a rat model of acute myocardial infarction followed by cardioplegic arrest, application of BCP leads to better myocardial recovery than CCP. Acute myocardial infarction can be treated by either percutaneous coronary intervention or coronary artery bypass grafting surgery (CABG) . In thisThe goal of this study was to compare the influence of CCP and BCP on cardiac function, metabolism, and infarct size in a rat heart model of myocardial infarction.This study investigated the effect of different two different cardioplegia solutions on isolated infarcted rat hearts in the experimental setting of a blood-perfused Langendorff apparatus. Control hearts underwent the same experimental procedure without induction of a myocardial infarction.A Langendorff apparatus  was filled with freshly prepared, filtered, heparinized bovine erythrocyte concentrates and warmed to a temperature of 36 °C. Physiological conditions were maintained: the hemoglobin content of our perfusion solution was between 6.0 and 7.0 mg/dl. End-diastolic pressure was adjusted to 10–12 mmHg by adding or subtracting volume from the balloon during the first perfusion period of 30 min. After starting the experiment by clamping the aorta, the volume was kept constant. The model has already been described in more detail . After eIsovolumetric measurement of left ventricular (LV) performance was carried out using a compliant latex balloon  inserted in the LV across the mitral valve that was connected to a pressure transducer. The volume of the saline-filled balloon was kept constant during the entire experiment. LV performance was assessed by measurement of LV systolic pressure (LVSP) and LV end-diastolic pressure . Positive and negative first derivatives of LVSP  were recorded by a transducer-amplifier module  and calculated by the software “Isoheart” (Harvard Apparatus). While aortic pressure was held at a constant 70 mmHg by a pressure controller, coronary flow (ml/min) was measured. The results were calculated as percent of baseline to correct for initial differences  male Wistar rats  were quickly excised, cannulated, and inserted into the blood-perfused isolated heart apparatus. A total of 18 hearts underwent acute myocardial infarction, as described above. Thereof, 9 hearts were protected with cold Buckberg BCP and 9 with cold Bretschneider CCP. A total of 32 hearts served as control groups with 16 hearts in the cold Buckberg BCP group and 16 hearts in the cold Bretschneider CCP group, respectively. All experiments were approved by the regional authorities and conformed to the German Animal Protection Law.Cold Buckberg BCP was administered in a 4:1 (blood:BCP) dilution. BCP was prepared using the bovine erythrocyte solution used for perfusion of the hearts and a commercially available solution . The BCAfter 90 min of reperfusion, the hearts of the infarction group were removed from the perfusion apparatus and frozen at − 20 °C for 30 min. Subsequently, hearts were cut into 7–8 slices and incubated in 1.2% triphenyl tetrazolium chloride for 20 min at 37 °C. Heart slices were then fixed in 7% formalin at room temperature overnight. Digital images were taken of both sides of the heart slices with a M60 microscope  at 2.5-fold magnification. Infarct size was determined by planimetry using the Leica Application Suite LAS version 4.6 (Leica).p < 0.05.Hemodynamic parameters obtained at different time points after the end of cardioplegia or opening of the aortic clamp were expressed relative to baseline (BL) and analyzed using SPSS statistical software version 24 . Intergroup differences in hemodynamic parameters and results of cardiac metabolism (response variables) over time were analyzed using two-way ANOVA  models with “time points”  as the within-subject factor and “group”  as the between-subjects factor. Tukey’s post-hoc test was used if any difference was observed. The infarct sizes were compared between the groups using a two-sided Student’s t-test. Data are shown as mean ± SD. Statistical significance was assumed at a level of p = 0.0062]]; dp/dt max. 73 ± 11% vs. 23 ± 2.7% [p = 0.0001]; Fig. p = 0.99]) in both types of cardioplegia .Cardiac function after acute myocardial infarction and 90 min of cardioplegic arrest was better preserved with Buckberg BCP than with Bretschneider CCP (LVDP 54 ± 11% 9 ± 2.9% [p = 0.029) and myocardial necrosis was distributed unevenly to the left ventricular wall  57 mmHg vs. peak(BCP) 18 mmHg; p = 0.0002) and in the control (peak(CCP) 56 mmHg vs. peak(BCP) 13 mmHg; p = 0.0001) hearts.The infarct pattern was different between hearts perfused with BCP or CCP. With BCP, the infarct was small (25% of myocardium) and limited to the area of LAD ligation, whereas with CCP, the infarct was larger  investigated in this setting. The effects of other (shorter or longer) clamping times on the efficiency of different protection strategies (eg. development of infarct size) remain to be investigated in further experiments. In addition, we used a buffered bovine erythrocyte suspension in our model instead of whole rat blood, and we cannot be sure how this influenced our findings. Furthermore, cardioplegia delivery to the infarcted LAD area was probably impaired due to the LAD ligature. The extent of collaterals could not be evaluated individually. Therefore, the real protection of the LAD territory achieved during the experiment remains somewhat elusive. However, we chose this model in order to simulate the clinical setting, where delivery of cardioplegia to the infarct area can also be difficult. However, clinically used approaches to deliver cardioplegia to the infarct area  could not be incorporated in this experimental model.Despite these limitations, no other experimental model comes closer to the clinical setting. With our model, we were able to exclude patient characteristics that can influence the findings in clinical settings. Moreover, the endpoints used in the clinical setting are often too general or too noninvasive to be able to observe slight differences and changes in the myocardium of patients.In the investigated isolated rat heart model of acute myocardial infarction followed by cardioplegic arrest, BCP leads to better myocardial recovery than CCP which may be considered in the clinical use of surgical revascularization in patients with acute myocardial infarction.