The optimal cardiovascular screening strategy among survivors of cancer diagnosed at age 39 years or younger has not been determined. This retrospective analysis examined the role of echocardiography-based myocardial strain in identifying survivors at risk for left ventricular dysfunction. In this population, longitudinal and circumferential strain can likely improve the identification of survivors at risk for cardiovascular dysfunction and provide an opportunity for early intervention.p = 0.039, as well as FS and CS −0.413, p < 0.001. The area under the curve for an FS ≤ 27% was 91%. Among C-AYAs, myocardial strain measurements may improve the identification of individuals with cardiotoxicity, thereby allowing earlier intervention.Cardiovascular disease is a leading contributor to mortality among childhood, adolescent and young adult (C-AYA) cancer survivors. While serial cardiovascular screening is recommended in this population, optimal screening strategies, including the use of echocardiography-based myocardial strain, are not fully defined. Our objective was to determine the relationship between longitudinal and circumferential strain  and fractional shortening (FS) among survivors. This single-center cohort study retrospectively measured LS and CS among C-AYAs treated with anthracycline/anthracenedione chemotherapy. The trajectory of LS and CS values over time were examined among two groups of survivors: those who experienced a reduction of >5 fractional shortening (FS) units from pre-treatment to the most recent echocardiogram, and those who did not. Using mixed modeling, LS and CS were used to estimate FS longitudinally. A receiver operator characteristic curve was generated to determine the ability of our model to correctly predict an FS ≤ 27%. A total of 189 survivors with a median age of 14 years at diagnosis were included. Among the two survivor groups, the trajectory of LS and CS differed approximately five years from cancer diagnosis. A statistically significant inverse relationship was demonstrated between FS and LS −0.129,  Cardiovascular disease is a leading contributor to late morbidity and mortality after cancer treatment ,2,3. WheQuantitative two-dimensional (2D) assessments of left ventricular (LV) systolic function measured by left ventricular ejection fraction (LVEF) or fractional shortening (FS) have historically been the focus of cardiac surveillance. Unfortunately, the ability of LVEF and FS to identify asymptomatic survivors who are at risk for treatment-related cardiotoxicity can be limited ,10,11. ALV strain, which is an assessment of myocardial deformation, can indicate cardiovascular dysfunction prior to a decline in LV systolic function. In patients with adult-onset malignancies, baseline longitudinal strain (LS) and early changes in LS during therapy are superior metrics to identify patients at a higher risk for subsequent cardiovascular events, including heart failure ,14,15,16We hypothesized that in C-AYAs, LS and circumferential left ventricular systolic strain (CS) would be associated with future FS values. To test this hypothesis, we performed a retrospective analysis of LS and CS in a cohort of C-AYAs treated with cardiotoxic chemotherapy.This retrospective cohort analysis was reviewed and approved by the Institutional Review Board. An existing database of 484 patients with sarcoma, Hodgkin lymphoma, or acute myeloid leukemia treated at Vanderbilt University Medical Center between 2001 and 2019 was reviewed. Subjects were included if they were treated by the pediatric hematology/oncology program with anthracyclines or anthracenediones, such as mitoxantrone, and had adequate clinical records to determine diagnosis, therapeutic regimen, and cardiovascular history. Subjects were required to have one pre-therapy and one or more post-therapy echocardiograms available with DICOM images of adequate quality for retrospective analysis. Subjects were not included if clinical remission could not be achieved. If relapse occurred less than 1 year after the original end of treatment, the end of therapy date was defined as the date after completion of both initial and salvage therapy. If relapse occurred more than 1 year after the original end of treatment, the end of therapy date was defined as the date of completion of the initial treatment regimen. In this scenario, echocardiograms, cancer therapy, and cardiovascular outcomes prior to the date of relapse were included in the analysis.Individuals for whom cardiac screening and management likely differed from the broader survivor population were excluded. This included individuals with pre-treatment echocardiograms demonstrating greater than mild mitral or aortic valve regurgitation/stenosis, greater than moderate tricuspid or pulmonary valve regurgitation/stenosis, hemodynamically significant congenital heart disease , greater than moderate pericardial effusion, constrictive physiology, an FS < 28% (as quantified by 2D or M Mode methods), an LVEF < 55% , an arrhythmia (not isolated PACs or PVCs), a family history of cardiomyopathy, or evidence of non-compaction/infiltrative cardiomyopathy.Data including gender, race, type of malignancy, age at diagnosis, total anthracycline/anthracenedione dose, and radiation to a field with potential impact on the heart were obtained from a review of the electronic health record. Doxorubicin isotoxic equivalents were calculated and relevant radiation fields were identified based on the Children’s Oncology Group Long-Term Follow-Up Guidelines Version 5 .Echocardiograms performed at our institution from the time of cancer diagnosis and onwards were identified. Echocardiograms were performed on commercially available equipment . Clinical echocardiogram reports were reviewed. The pertinent clinical findings, including measurements of LVEF and FS, and evidence of valvular disease, pericardial disease, or other cardiac pathology were recorded.DICOM images were imported into a research database and analyzed using Cardiac Performance Analysis 4.6 . For all studies with adequate image quality, LS and CS were measured by tracing endocardial borders in the apical four-chamber view and short-axis view at the mid-papillary level. Image analysis was performed and reviewed by a core group of 3 sonographers and 1 cardiologist who were blinded to the clinical outcome. All data were compiled and stored in REDCap, a HIPAA compliant electronic database .To determine the trajectory of LS and CS over time, survivors were divided into two groups. Based on reproducibility data indicating a decline in FS by >5 absolute units is clinically significant , we dichThe random intercept mixed model was used in this longitudinal analysis to determine the relationship between CS, LS and FS as time proceeds. All available time points were included in the analysis. In addition to LS and CS, the following demographic and treatment factors were identified a priori and included as explanatory variables in the analyses: age at diagnosis, total doxorubicin isotoxic equivalents, and radiation to a field involving the heart (yes/no). Given a variable duration of follow-up, the time elapsed since diagnosis was also included in the model. The two-sided significance level was set to 5% for assessing the significance of the estimated parameters.We assessed the relationship between FS and strain measurements using three models: (a) LS individually; (b) CS individually; and (c) LS and CS combined. The root mean square error (RMSE) was determined for all three models and the Diebold–Marino test was used to compare the predictive accuracy of the 3 models .We performed a post hoc analysis using a receiver operator characteristic curve to determine the ability of our model to correctly predict an FS ≤ 27%, a clinically accepted marker ofabnormal left ventricular systolic function . The anaOur initial chart review identified 206 unique subjects who met inclusion criteria. Among subjects who were not included, the most common reasons were unavailable digital echocardiograms (72%) and not achieving remission (17%). The remaining reasons for exclusion were unclear treatment history, no exposure to anthracyclines, and significant congenital heart disease.A total of 199 subjects had DICOM images of adequate quality with appropriate tracking of LV motion to perform measurements of left ventricular strain . Due to 2 IQR (200 mg/m2 to 375 mg/m2). A total of 32.3% (61/189) of the participants had received radiation. The median follow-up time was 1.8 years with an IQR of 0.8 to 4.8 years , acute myeloid leukemia 24% (45/189), and Ewing sarcoma 22% (42/189). The median doxorubicin isotoxic equivalence dose was 300 mg/m.8 years . ApproxiThe pre-treatment median FS was 37.1% IQR (34.7% to 40.1%). The pre-treatment median LS was −19.8% IQR (−21.9% to −18.1%) with a pre-treatment median CS of −25.6% IQR (−28.6% to −22.9%). The median FS on the most recent follow-up was 35.0% IQR (32.0% to 38.0%) with a median LS of −18.7% IQR (−20.9% to −16.7%) and a median CS of −24.3% IQR (−26.9% to −21.9%) .By plotting LS over time for both FS groups, we determined that approximately five years from cancer diagnosis, the rate of change in LS began to differ between the two groups with a larger rate of decline among individuals with a reduction of >5 FS units when compared with individuals without a reduction of ≥5 FS units a. Similap < 0.001). For every one-unit increase in LS and CS, FS decreased by 0.13 and 0.41 units, respectively. We found no significant interaction between time and LS or CS. Using a mixed-effects model, we identified significant inverse relationships between FS and the following variables: time since diagnosis, LS, and CS . For eveNext, we examined LS and CS individually. By comparing plots of LS and estimated FS to plots of CS and estimated FS, we determined that there was a higher rate of change between CS and estimated FS when compared to LS and estimated FS a,b. ThisTo better understand the relationship between LS, CS, and FS, we determined the RMSE for all three models based on LS alone (RMSE 4.21), CS alone (RMSE 4.07), and both LS and CS (RMSE 4.05). Only the model that included both LS and CS did not violate the normality assumptions. We also assessed differences in the forecasted accuracy of the three models using the Diebold–Mariano test . The DieOur post hoc analysis used an FS value of ≤27% as a marker of clinically significant LV dysfunction. The area under the curve (AUC) for the receiver operating characteristic curve (ROC) generated by our data is 0.906  with an AUC of 0.900 for the corresponding smoothed ROC . . This imThe role of strain in cardiovascular screening among C-AYAs is poorly defined. Our study specifically examines the association between LS, CS, and FS in a retrospective single-center cohort. Our main finding shows that a model using LS and CS to estimate future FS can accurately identify survivors at risk for LV dysfunction (defined as an FS ≤ 27%). Additionally, the rate of change in LS and CS starting five years post-cancer diagnosis may differ between survivors who develop a clinically significant decline in FS and those who do not. Therefore, using LS and CS during cardiac screening may identify survivors at a higher risk of future cardiotoxicity, and thereby provide an opportunity for earlier clinical intervention.Although FS and LVEF are commonly used during cardiac screening, evidence suggests that relying on these late biomarkers of cardiotoxicity is likely suboptimal. Cardinale et al. has demonstrated that 36% of adults treated with anthracycline-based chemotherapy who develop an LVEF ≤ 45% will not achieve complete recovery of LV systolic function, even if heart failure therapy begins immediately . SimilarStrain can also provide a more effective strategy for timing the initiation of medical therapy. In an adult population, an LS-guided strategy for initiation of heart failure therapy (≥12% relative reduction in LS) during cancer treatment has demonstrated superior preservation of cardiac function compared to an LVEF-guided strategy (>10% absolute reduction in LVEF) . PromisiThere are population-specific considerations when utilizing strain measurements. LS is preferentially emphasized over CS in adult-based cardio-oncology guidelines. However, studies have indicated that CS values were abnormal more often than LS values in C-AYAs greater than one year after treatment ,28. In tAnother unique aspect of cardiovascular screening in C-AYAs is the longevity of survivors, leading to an extended duration for follow-up and serial surveillance. Based on our data, changes in the trajectory of myocardial strain may begin to differentiate between lower- and higher-risk groups approximately five years from a cancer diagnosis, making this an ideal time to enhance screening.Our study suggests a potential role for strain as an imaging biomarker for identifying survivors at a higher risk for the development of subsequent LV dysfunction. However, several limitations should be noted when interpreting these results: (a) The largest limitation is the retrospective nature of this study, which caused variability in available retrospective echocardiogram images and image quality. Although this limitation is not unique to our study and is common to retrospective imaging studies in this population, this hindered our ability to perform a Simpsons’ bi-plane measurement of ejection fraction . Future In a retrospective single-center study of C-AYAs, we showed that measurements of LS and CS could provide estimates of future FS. The change in the trajectory of LS and CS values among patients who developed cardiotoxicity became apparent approximately five years after a cancer diagnosis. These results will require further validation in a large prospective cohort but suggest the potential utility of strain to stratify the risk for LV dysfunction among C-AYAs undergoing cardiac surveillance.


Diastolic dysfunction refers to a structural or functional abnormality of the left ventricle, resulting in impaired filling of the heart. Severe diastolic dysfunction can lead to congestive heart failure even when the left ventricle systolic function is normal. Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of the hospitalizations for acute heart failure in the adult population but the clinical recognition and understanding of HFpEF in children is poor. The condition is certainly much less frequent than in the adult population but the confirmatory diagnosis of diastolic dysfunction in children is also challenging. The underlying causes of HFpEF in children are diverse and differ from the main cause in adults. This review addresses the underlying causes and prognostic factors of HFpEF in children. We describe the pulmonary hypertension profiles associated with this cardiac condition. We discuss diagnosis difficulties in clinical practice, and we provide a simplified diagnostic algorithm for HFpEF in children. It can be defined as the capacity of the heart to relax and distend during diastoles leading to fulfilling of the LV chamber up to an appropriate telediastolic volume. Diastolic dysfunction is defined by the incapacity of the ventricle to fill in even if the atrial pressure is normal. Diastolic dysfunction might be due to a prolonged relaxation or/and an increased stiffness of the ventricle . The norToday, the commonly used definition is heart failure with a left ventricle ejection fraction (LVEF) >50% associated with evidence of spontaneous or provokable increased left ventricle (LV) filling pressures . There i2.LV diastolic dysfunction has been well studied and described in adults as HFpEF accounts for at least half the patients diagnosed with heart failure . Risk fa3.HFpEF is a heterogeneous group of diseases characterized by symptoms of heart failure due to increase in myocardial stiffness. The physiology and cellular mechanism of HFpEF depends on the cause and involves, among other things, cardiac hypertrophy and fibrosis , intrinsIn restrictive cardiomyopathy (RCM), LV wall thickness is more often within normal limits and for Gewillig the pathophysiology of RCM is related to myocyte abnormality such as myocyte hypertrophy, enlarged, irregular and hyperchromatic myocyte nuclei . GeneticIn the study of Lombardi et al. , a lineaInterstitial myocardial fibrosis also plays a role in the pathogenesis of the LV diastolic dysfunction as it increases ventricular rigidity and compromise the stretching capability of the myofibrils . Collage4.The causes of LV diastolic dysfunction in children differs substantially from the classical risk factors identified in adults, intrinsic myocytes abnormality seems to be the leading cause of diastolic dysfunction in children. Primary cardiomyopathies are diseases of the heart muscle in which the myocardial dysfunction appears in the absence of systemic comorbidities, valvular or congenital heart disease . Hypertr4.1.Dilated cardiomyopathy (DCM) is defined by the presence of a dilated LV with systolic dysfunction without any hemodynamic, physiological, ischemic or anatomic cause . DCM accHypertrophic cardiomyopathy (HCM) is defined by an hypertrophied and non-dilated ventricle in the absence of a hemodynamic cause of wall thickening, excluding physiological hypertrophy  and pathological hypertrophy  . HCM is Diastolic dysfunction has been described mainly in children suffering from restrictive cardiomyopathy, accounting for less than 5% of pediatric cardiomyopathy cases , 26. Lea4.2.LV diastolic dysfunction has been described in patients with aortic coarctation or aortic stenosis , 24, 35 Some extrinsic factors have also been described in children such as inflammatory diseases: acute myocarditis , KawasakTransient LV diastolic dysfunction can be observed in acute contexts such as tachycardia, during the early post-operative period or during sepsis. It is important to note that at birth (during the first 7 days/the first two months for preterms) the diastolic properties of the LV are significantly impaired without pathological significance.As for adults, renal insufficiency –44 and o5.In some cases, diastolic dysfunction may not cause any symptoms and may only be suspected during a routine echocardiography. In other cases, it can cause symptoms such as shortness of breath, atypical asthma, and syncope. The clinical signs that may suggest the presence of diastolic dysfunction include increased jugular venous pressure, hepatomegaly, oedema and ascites . Lack of6.Group 2 pulmonary hypertension includes PH associated with left heart disease including HFpEF, heart failure with reduce ejection fraction, valvular heart diseases and congenital heart diseases. Despite similar hemodynamic profiles, there are significant disparities between these patients' groups in terms of comorbidities and clinical phenotypes . The hem7.The clinical recognition and understanding of heart failure with preserved ejection fraction in children is poor. This might be because it is a rare condition but also because the diagnosis of diastolic dysfunction in children is difficult in clinical practice. The symptoms may be subtle and can vary depending on the severity of the condition. The consensual definition of HFpEF is the presence of signs and symptoms of heart failure, a LV ejection fraction >50% associated with evidence of spontaneous or provokable increased LV filling pressure .τ) that reflects the rate of decline of LV pressure during the isovolumic relaxation period (IVRT). Normal duration of tau is 30–40 ms (The gold standard to characterize LV relaxation is cardiac catheterization. A high-fidelity catheter placed into the LV measure simultaneously LV volumes and pressure. The LV pressure-volume loops reflects the filling and contractile properties of the ventricle . The com30–40 ms . (2) Pul30–40 ms . Indeed,2/m2 (range 16.9–28.6) vs. 10.3 cm2/m2 (range 8.3–12.3) in the control group . The H2FPEF  and the ol group . By provol group . There iol group . In the ol group , it appeP < 0.05) and “ROC curve analysis showed that an aldosterone/ BNP ratio of 10.3 or higher best predicted HFpEF [area under the curve (AUC) = 0.89], with a sensitivity of 0.67 and specificity of 1.0.”.The B-type natriuretic peptide (BNP) and its pro-hormone NT-proBNP  are produced by the ventricles in response to increased pressure or volume loads. It is typically released when the myocytes are stretched or under stress  NT-proBNCardiac magnetic resonance imaging (CMRI) is a non-invasive imaging modality that can provide valuable information about the structure and function of the heart. By providing details about myocardial phenotype such as the localization of the myocardial hypertrophy  in HCM or the specific myocardial composition such as the presence of fibrosis, edema, fat, iron overload (by T2* imaging) in patients with hemochromatosis  CMRI is 8.The clinical course of children with diastolic dysfunction varies depending on the underlying cardiac condition. Global prognosis of HFpEF in children is uncertain especially since this term refers to a heterogeneous group of patients. There is limited literature on the prognosis of HFpEF in children beyond the phenotypes of HCM and RCM. No well-defined predictors exist for determining survival after diagnosis but it appears that RCM prognosis is grim due to the risk of sudden death and progression of pulmonary hypertension leading to early transplantation , younger9.It is important for children with left ventricular diastolic dysfunction to receive timely and appropriate treatment to help prevent any long-term complications. To date, there is no pharmaceutical drug facilitating myocardial relaxation or improving ventricular compliance. Also, pharmaceutical treatment for HFpEF in children is extrapolated from adult clinical trials. Lifestyle management in children includes fighting against obesity and poor diet, blood pressure control and physical activity. Medical management strategies include diuretics to relieve symptoms of congestive heart failure. In adults' patients, the precise monitoring of the pulmonary pressures through a device, the CardioMEMS Heart Sensor, allows for efficient diuretic titration and has proven its benefit in reducing hospitalization for heart failure in patients suffering from HFpEF , 80. Bet10.HFpEF is a rare and probably under-diagnosed condition in children. It can be caused by a variety of underlying conditions. Clinical presentation is not specific, and the diagnosis may be difficult. We proposed a diagnosis algorithm easy to use in clinical practice. Prognosis depends on the cause, but the appearance of associated hypertension marks a turning point in the evolution of the disease. Specific treatments are limited.


T1, T2 and T1ρ are well-recognized parameters for quantitative cardiac MRI. Simultaneous estimation of these parameters allows for comprehensive myocardial tissue characterization, such as myocardial fibrosis and edema. However, conventional techniques either quantify the parameters individually with separate breath-hold acquisitions, which may result in unregistered parameter maps, or estimate multiple parameters in a prolonged breath-hold acquisition, which may be intolerable to patients. We propose a free-breathing multi-parametric mapping (FB-MultiMap) technique that provides co-registered myocardial T1, T2 and T1ρ maps in a single efficient acquisition.The proposed FB-MultiMap performs electrocardiogram-triggered single-shot Cartesian acquisition over 16 consecutive cardiac cycles, where inversion, T2 and T1ρ preparations are introduced for varying contrasts. A diaphragmatic navigator was used for prospective through-plane motion correction and the in-plane motion was corrected retrospectively with a group-wise image registration method. Quantitative mapping was conducted through dictionary matching of the motion corrected images, where the subject-specific dictionary was created using Bloch simulations for a range of T1, T2 and T1ρ values, as well as B1 factors to account for B1 inhomogeneities. The FB-MultiMap was optimized and validated in numerical simulations, phantom experiments, and in vivo imaging of 15 healthy subjects and six patients with suspected cardiac diseases.The phantom T1, T2 and T1ρ values estimated with FB-MultiMap agreed well with reference measurements with no dependency on heart rate. In healthy subjects, FB-MultiMap T1 was higher than MOLLI T1 mapping . The myocardial T2 and T1ρ estimated with FB-MultiMap were lower compared to the mapping with T2- or T1ρ-prepared 2D balanced steady-state free precession . The pathological changes in myocardial parameters measured with FB-MultiMap were consistent with conventional techniques in all patients.The proposed free-breathing multi-parametric mapping technique provides co-registered myocardial T1, T2 and T1ρ maps in 16 heartbeats, achieving similar mapping quality to conventional breath-hold mapping methods.The online version contains supplementary material available at 10.1186/s12968-023-00973-6. Quantitative cardiac magnetic resonance (MR) parametric mapping has emerged as a promising non-invasive tool for characterizing myocardial tissue, diagnosing various cardiovascular diseases, and monitoring treatment effects –3. The rT1, T2 and T1ρ parameters provide complementary information about the myocardium, and a combination of multiple parameters may improve diagnostic sensitivity and boost diagnostic confidence for suspected cardiomyopathy , 20. HowSimultaneous multi-parametric mapping techniques have been proposed to overcome the limitations of separate mapping methods. Previous cardiac multi-parametric mapping approaches are mostly for T1 and T2 mapping, which can be generally classified into two categories. The first category involves sophisticated sequence design by interleaving saturation, inversion and T2 preparation pulses so that the acquired multi-contrast images can be fitted to an analytical formula for T1 and T2 mapping –31. The The objective of this study is to propose a free-breathing multi-parametric mapping (FB-MultiMap) technique that enables B1 inhomogeneity-corrected simultaneous myocardial T1, T2 and T1ρ mapping with single-shot Cartesian acquisition and dictionary matching. Inspired by previous studies that leverage the diaphragmatic navigator (dNAV) for free-breathing parameter mapping , 40, 41,An overview of the proposed free-breathing multi-parametric mapping technique is provided in Fig. x-SLy-SL-y-180°-x-SL-y-SLy-90°x pulses cluster, where the SL pulse is equally divided into four segments. As shown in the previous T1ρ-prep optimization studies  ms for T1; [10:2:160] for T2 and T1ρ;  for B1. Combinations of T2 > T1 and T1ρ > T1 were excluded from the dictionary simulation. The Bloch simulations were implemented using MATLAB  and the dictionary generation took about 6 min on a workstation  with parallel computing.The in vivo imaging was approved by the local institutional review board. Fifteen healthy subjects  and 6 patients with suspected cardiomyopathy  were imaged after obtaining written informed consent. The demographic information and referral reasons of the patients are summarized in Table The optimized FB-MultiMap was evaluated against the breath-hold separate mapping methods: MOLLI 5(3)3 for T1 mapping , T2-prepThe dictionary generated for in vivo studies contained about 2,330,000 T1/T2/T1ρ/B1 combinations:  ms for T1,  for T2 and T1ρ, and  for B1. It took about 1.5 min for the subject-specific dictionary generation and 10 s for extracting parametric maps per slice using dictionary matching.For phantoms, the mean and SD were calculated for each tube. The estimations of FB-MultiMap and sFB-MultiMap were then respectively compared with the reference methods using Pearson correlation. Bland–Altman analysis was also conducted to evaluate the agreement of FB-MultiMap with the reference methods. For in vivo images, region-of-interests were manually defined in the T1, T2 and T1ρ maps according to the 16-segment of the American Heart Association (AHA) model . SubsequThe optimized FB-MultiMap is demonstrated in Fig. FA1/FA2 in Fig. FA1/FA2 combinations resulted in the lowest RRMSE for all parameters, with T1 favoring 45°/70°, while T2 and T1ρ favoring low FA1 of 35° and moderate FA2 of 50°. Therefore, we subsequently proposed to also alter the flip angles after the first T2-prep and the first T1ρ-prep pulse, resulting in a four-flip-angle strategy, FA1-1, FA1-2, FA2-1 and FA2-2 in Fig. FA1-1 and FA2-1, while T2 and T1ρ RRMSE was respectively more influenced by FA1-2 and FA2-2, the appropriate four flip angle combination can be inferred from the dual flip angle results with FA1-1 (45°) and FA2-1 (70°) being the optimal flip angles for T1 and B1 and FA1-2 (35°) and FA2-2 (50°) being the optimal flip angles for T2 and T1ρ. The inferred four-flip-angle strategy (45°/35°/70°/50°) avoids the brute-force search for the optimal combination of four flip angles that would require prohibitively long computation time. Figure For the variable flip angle strategy, the dual flip angle scheme was initially tested with the excitation flip angle changed after the second IR . Increasing the TSL in T1ρ-prep may help to improve FB-MultiMap estimation accuracy for longer T1ρ.In healthy subjects, FB-MultiMap achieved similar mapping quality to BH-MultiMap, indicating that after motion correction, respiratory motion has little influence on parameter quantification of FB-MultiMap. The FB-MultiMap T1 was higher than MOLLI, which may suggest improved T1 accuracy of FB-MultiMap as MOLLI is known to underestimate T1 , 56. HowCardiac diseases are usually complex, involving more than one type of pathological change in myocardium. There is where multi-parametric mapping techniques could come into play to aid in diagnosis with comprehensive myocardial tissue characterization. The feasibility of FB-MultiMap in detecting cardiomyopathies has been demonstrated in several patients. The pathological changes detected with FB-MultiMap agreed with conventional breath-hold mapping methods. Specifically, increased T1 and T1ρ values were observed for all the LGE-positive patients in the enhancement area, indicating their potential for detecting myocardial fibrosis without contrast agent. The deposition of lysosomal sphingolipids in Fabry disease leads to low T1 values, which were detected by both FB-MultiMap and MOLLI. In one Fabry patient Fig. A, the baThere are several limitations in this study. Although efforts were made to optimize the variable flip angle three-parameter mapping technique, the optimization was limited to several empirically designed candidate sequences. Exploring more complex preparation pulse configurations and variable flip angle schemes may help to further improve accuracy and precision. The diaphragm navigator based through-plane motion correction was performed with fixed slice-tracking factor. Adopting a patient-specific motion model trained in a calibration scan to characterize the heart motion relative to dNAV  may helpThe proposed approach enables simultaneous native myocardial T1, T2 and T1ρ mapping with B1 correction using single-shot Cartesian acquisition and dictionary matching during free breathing. FB-MultiMap demonstrated good agreement with reference techniques in phantoms and achieved similar mapping quality to conventional breath-hold mapping techniques. The multi-parametric mapping technique also demonstrated promising results in detecting pathological changes in T1, T2 and T1ρ. With efficient free-breathing acquisition and simple post-processing, FB-MultiMap has great potential for clinical applications.Additional file 1. Optimization of the multi-parametric mapping sequence, additional results of variable flip angle strategy optimization, additional patients results, influence of off-resonance, and influence of inversion efficiency.


Early heart failure prevention is central in patients with type 2 diabetes, and mineralocorticoid receptor antagonists (MRAs) have shown to improve prognosis. We investigated the effect of high-dose MRA, eplerenone, on cardiac function and structure in patients with type 2 diabetes and established or increased risk of cardiovascular disease but without heart failure.In the current randomized, placebo-controlled clinical trial, 140 patients with high-risk type 2 diabetes were randomized to high-dose eplerenone (100–200 mg daily) or placebo as add-on to standard care for 26 weeks. Left ventricular systolic and diastolic function, indexed left ventricular mass (LVMi), and global longitudinal strain (GLS) were assessed using echocardiography at baseline and after 26 weeks of treatment.P = 0.992) or E/A . Mean left ventricular ejection fraction (LVEF) at baseline was 59.0% (8.0). No improvement in systolic function was observed when comparing groups after 26 weeks , nor in LVMi .Of the included patients, 138 (99%) had an echocardiography performed at least once. Baseline early diastolic in-flow velocity (E-wave) indexed by mitral annulus velocity (e’) was mean (SD) 11.1 (0.5), with 31% of patients reaching above 12. No effect of treatment on diastolic function was observed measured by E/e’ .The online version contains supplementary material available at 10.1186/s12872-023-03183-1. In patients with type 2 diabetes, the risk of heart failure hospitalization as the first cardiovascular event exceeds myocardial infarction by approximately a factor four . UndiagnExperimental evidence has proven that inhibition of the mineralocorticoid receptor is an important therapeutic target in the prevention of cardiovascular disease in animal models of diabetes, obesity and early heart failure –11. FurtIn this substudy of the Mineralocorticoid Receptor Antagonist in type 2 Diabetes (MIRAD) trial, we aimed to investigate whether high-dose eplerenone as an add-on therapy improves left ventricular function evaluated by echocardiography. In the present study we report the prespecified, secondary endpoints of left ventricular systolic and diastolic function, including global longitudinal strain (GLS), after 26 weeks of treatment with the MRA, eplerenone.th week, and thereupon every four weeks until completion of the trial as a part of the prespecified protocol. The treatment drug and placebo, provided by Glostrup Pharmacy, could not be distinguished from each other. The trial included patients with a diagnosis of type 2 diabetes and concurrent cardiovascular disease or a high risk thereof defined by the following key inclusion criteria: previous myocardial infarction, significant stenosis on coronary angiography, previous stroke or transient ischemic attack at least 3 months prior to randomization, presence of peripheral artery disease, NT-proBNP ≥ 70 ng/L  and two-tailed unadjusted p-values. A p-value below 0.05 considered as statistically significant. Data-transformation was used to adhere to model assumptions and results are presented after de-transformation. Statistical analyses and graphical design were performed using SAS (version 9.4 TS 1M5) , GraphPad Prism 8, version 8.1.0 , and n = 61; placebo n = 63). In the final analysis, 138 patients with at least one echocardiography were included , missing two patients from the eplerenone group. Of these patients, an echocardiography was performed on 124 patients after week 26 (89%)  received a dose of 100 mg daily or above from week 8 until week 26. In comparison, among patients with an estimated glomerular filtration rate below 60 mL/min/1.73m2 (n = 12), only 29% in the eplerenone group received 100 mg at week 26 , P = 0.191) (Table P = 0.277)  E/e’ was 11.1 (0.5), and patients with diastolic dysfunction, defined by an E/e’ above 12, comprised 31% of the study population (Table P = 0.382) (Table P = 0.876). As an effect, no treatment effect was observed on GLS when comparing groups at week 26 . The addition of eplerenone did not elicit an observable change in LVMi when comparing groups at week 26, with a non-significant treatment effect of -3.8 g/m2  , with 86% of the population having an LVEF above 50%. Following the addition of eplerenone, neither EDV nor ESV changed from baseline in either group or when comparing groups at week 26. There was no change in LVEF when comparing groups at week 26 (0.9, 95%CI -1.1 to 2.8], .1 to 2.8Evaluating additional measures of left ventricular function obtained using a conventional echocardiography protocol, we observed no significant effect of treatment when comparing groups at 26 weeks (Supplementary table In the present echocardiography sub-study of the MIRAD trial, no improvement was observed in either systolic, diastolic left ventricular function or LVMi following treatment with high-dose eplerenone for a duration of 26 weeks in a cohort of high-risk type 2 diabetes patients without known heart failure.The increased risk of cardiovascular disease following the diagnosis of type 2 diabetes is well-established, with the concomitant diagnose of heart failure further substantially impairing prognosis . The cliWe did not observe an effect of high-dose MRA therapy on systolic ventricular function in this cohort without HFrEF. The lack of a change in a cohort of patients in stable antidiabetic and antihypertensive treatment without overt systolic dysfunction at baseline is in line with previous publications, where trials have yet to observe a consistent improvement in LVEF in patients without HFrEF following MRA therapy , 16. SimAlthough MRAs have long been used as antihypertensives, experimental studies in animal models investigating the underlying mechanisms of MRA therapy have demonstrated extra-renal, receptor-mediated effects shown to be independent of the expected diuretic and antihypertensive effects mediated by mineralocorticoid receptor activation in the distal tubules of the kidneys –10. FurtThe clinical benefit of finerenone as shown by the pooled-analysis, FIDELITY, as well as the recent advances in outlining the mechanism of extra-renal MRA therapy  has takeThe present study is a small, single-center study with a duration of only 6 months, and thus, is restricted in its ability to predict long-term changes in risk. Furthermore, the study is an exploratory analysis based on data from the MIRAD trial. Although the study focuses on left ventricular diastolic dysfunction, all outcomes are either secondary outcomes prespecified as part of trial design or defined post-hoc. As an effect – and in consideration of multiplicity of testing—results must be viewed as hypothesis-generating and in need of corroboration. Finally, the present study contained a large proportion of patients with no signs of either overt systolic or diastolic function, with a long-standing stable clinical condition, which lowers the expected effects size of treatment. Considering the results of PARAGON trial , a cohorIn patients with type 2 diabetes without HFrEF, the addition of high-dose eplerenone to standard therapy for a duration of 26 weeks was not associated with a detectable improvement in left ventricular systolic or diastolic function when measured using echocardiography.Additional file 1.


Stereotactic body radiotherapy (SBRT) has emerged as a promising treatment for patients with ventricular tachycardia (VT) who do not respond to standard treatments. However, the management of respiratory motion during treatment remains a challenge. This study aimed to investigate the effect of abdominal compression (AC) on respiratory induced motion in the heart.A patient cohort of 18 lung cancer patients was utilized, where two four-dimensional computed tomography (4DCT) scans were performed for each patient, one with and one without AC. The patient setup consisted of an AC plate together with a stereotactic body frame. The left coronary artery, the left anterior descending artery, the lateral wall of the left ventricle, the heart apex, the carina, and the right and left diaphragm were delineated in max expiration and max inspiration phases in both 4DCT scans. The center of mass shift from expiration to inspiration phase was determined to assess the AC’s impact on respiratory motion.A significant reduction in motion in the superior-inferior direction was found for all heart structures when AC was used. The median respiratory motion of the heart structures decreased by approximately 1–3 mm with AC in the superior-inferior direction, and approximately 60% of the patients had a motion reduction ≥3 mm in the left ventricle wall.These findings suggest that AC has the potential to improve the motion management of SBRT for VT patients, by reducing the respiratory induced motion in the heart. Most patients suffering from VT have an underlying heart disease Generally, different imaging modalities are used for target delineation. Electrophysiological imaging of the heart is done either with electro-anatomical mapping or non-invasive electrocardiographic imaging To minimize the irradiated volume, it is essential to decrease the motion of the heart. Hence, various motion management techniques should be evaluated for their potential to reduce motion. A common technique for respiratory motion reduction is abdominal compression (AC) 22.13 (range: 0.3–102.1 cm3).Due to the limited number of VT SBRT patients in this early stage, a surrogate patient cohort was utilised instead. Thirty lung cancer patients were retrospectively included in this study. The study was approved by the Swedish ethical review authority (No Dnr 2022-02382-02) and all patients signed informed consent. The patients had all undergone two 4DCT scans, one with AC and one without AC. After review of the data 12 of the patients were excluded due to either large motion artefacts in the 4DCT images or the heart not being fully included in the scanned volume. Characteristics of the included patients are presented in 2.2For compression the AC plate together with the stereotactic body frame  was used. The patients were positioned on a custom fitted vacuum pillow in the stereotactic body frame and the compression equipment consisted of an almost pentagon shaped compression plate of two different sizes and a compression screw of three different lengths. For each patient the most suitable plate and screw was used. The compression plate was placed just below the most caudal ribs and the screw was individually tightened to an acceptable level. The same level was used at both CT simulation and each treatment fraction. The patients were instructed to breathe as normally as possible with this forced shallow breathing. When constructing the custom fitted vacuum pillow, the stereotactic coordinates of both the position of the patient according to a tattoo on the sternum and the longitudinal position of the abdominal compression was set. At CT simulation and at each treatment fraction, the position of the patient and the abdominal compression was both adjusted to these stereotactic coordinates. Contrast was not used for any of the patients.For each patient two 10-phase respiratory 4DCT scans in a Somatom Definition AS+  was acquired. For respiratory signal generation the Sentinel  was used during image acquisition. The voxel size in the images was 0.98 × 0.98 × 2 mm. The lung was automatically segmented in both 4DCTs in the Eclipse (v 15.6) treatment planning system . The phase with the smallest lung volume was defined as maximum (max) expiration phase and the phase with the largest lung volume was defined as the max inspiration phase. In these two phases the following structures were delineated: the left coronary artery (LCA), the left anterior descending artery (LAD), the lateral wall of the left ventricle, the apex of the heart, the carina, and the right and left diaphragm. The LCA, LAD, carina and diaphragm were all delineated as small point structures, at first in the max expiration phase and thereafter in the same corresponding CT plane in the max inspiration phase. The heart apex was delineated in the two most inferior planes of the heart visible on the CT. The lateral wall of the left ventricle was delineated with the brush tool with a diameter of 1 cm, starting at the anterior top of the ventricle, down to the posterior part of the ventricle, along the lateral wall towards the lung . The sel2.3Using the statistics tool in Eclipse, the center of mass (COM) shift from max expiration phase to max inspiration phase was obtained in left–right (LR), anterior-posterior (AP), superior-inferior (SI) directions. The 3D vector length was calculated using 3The median 3D vector COM shift from max expiration to max inspiration phase was reduced by 1.9 mm for the LCA, 0.5 mm for LAD, 1.8 mm for the left ventricular wall, 4.1 mm for apex, 1.0 mm for carina, 7.6 mm for the right diaphragm and 5.5 mm for the left diaphragm . Median 4In this study the effect of AC on respiratory induced motion in the heart was evaluated. Results showed a statistically significant reduction of motion in SI direction for all delineated heart structures. The results also indicate that AC could decrease the median respiratory motion of heart structures by approximately 1–3 mm. This relatively small effect could still be of clinical significance given the very high dose that is delivered in only one fraction in SBRT of VT, with vital organs in close proximity to the target. The heart motion reduction could allow for PTV margin reduction, however evaluation of random and systematic errors of the VT patient population should be carried out first. Our results suggest that approximately 60% of the patients will have large (≥3 mm) motion reduction in SI direction when AC is utilised. However, 4 of 18 patients had an increase in motion using AC, indicating the need for individual evaluation. By performing one 4DCT without AC and one 4DCT with AC for each patient, the individual benefit of AC could be assessed.To our knowledge this is the first study to evaluate the effects of AC on respiratory induced motion in substructures of the heart. For instance, the motion of the left ventricle was examined, which is of particular interest for VT patients. Rasheed et al. In this study a straightforward comparison of motion with and without AC could be carried out since the data was paired. Since we did not have access to enough data for real VT patients, lung cancer patients were used as a surrogate cohort. The respiratory motion in the heart of a lung cancer patient might not be the same as in the heart of a patient suffering from VT. Nonetheless, we do still believe that these results give valuable information on how AC affects heart motion.To be able to compare the motion of the heart structures with other surrounding structures, the diaphragm and carina were delineated as well. AC did not reduce motion in the heart as much as it did for the diaphragm, which is to be expected, since the diaphragm is the key muscle for respiration. The motion of the carina was not significantly affected by AC implying that the thorax superior to the heart benefit less from AC.COM shifts are useful when studying small point structures, since the motion of COM closely corresponds to the motion of the structure. For larger structures however, such as the lateral left ventricle wall in this study, the COM motion may be less representative, since the ventricle deforms during both cardiac and respiratory cycle. Delineation on 4DCT phase images was challenging since it is more prone to motion artefacts than a regular CT. Moreover, the medial border of the left ventricle towards both the left atrium and the interventricular septum was also sometimes difficult to distinguish. Delineation uncertainties were therefore largest in the LR and AP direction in the left ventricle wall. To minimize delineation uncertainties, all structures were delineated by the same observer. Our results showed a statistically significant difference in motion between with and without AC in the SI direction, in which most respiratory induced motion occurs. Thus, despite delineation uncertainties these results do give an implication that AC could be beneficial for VT patients undergoing RT.As this study examined only one 4DCT with AC and one without AC for each patient, the reproducibility of patient breathing pattern or AC placement was not assessed. The primary objective of the current study was to investigate the potential motion reduction in the heart achieved using AC. However, considering that reproducibility is important for maintaining the motion reduction, it would be necessary to include AC placement evaluation when studying systematic and random errors in a potential PTV margin reduction.Although the majority of patients had a motion reduction of the heart using AC, there could be a risk of pushing the stomach towards the target volume with the AC. In the future, it would therefore be of interest to investigate whether the AC leads to dosimetric benefits as well.In conclusion, abdominal compression significantly reduced respiratory induced motion in the heart in the SI direction. Our results showed that a majority of the patients had a large (≥3 mm) motion reduction in the left ventricle wall when AC was used. However, a few patients had an increased heart motion, indicating the need for individual evaluation of AC.Annika Mannerberg: Conceptualization, Methodology, Formal analysis, Investigation, Data curation, Writing – original draft, Visualization. Martin P. Nilsson: Conceptualization, Methodology, Validation, Writing - review & editing. Anneli Edvardsson: Conceptualization, Writing – review & editing. Kristin Karlsson: Resources, Data curation, Writing – review & editing. Sofie Ceberg: Conceptualization, Writing – review & editing, Supervision, Project administration.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


Amyloidosis is the result of the extracellular deposition of amyloid in various organs. Common types are light-chain and transthyretin amyloidosis. Cardiac amyloidosis (CA) is a restrictive cardiomyopathy caused by amyloid infiltration in cardiac tissues. The detection of CA is increasing with the advent of easily accessible imaging modalities. Early diagnosis ensures a better prognosis. We present a case of cardiac amyloidosis, diagnosed from specific imaging findings on cardiac magnetic resonance imaging and more precisely as transthyretin type based on findings on nuclear scintigraphy. Amyloidosis is caused by the building up of proteins called amyloid in different organs. Endomyocardial biopsy is the definitive diagnostic modality of cardiac amyloidosis (CA) . HoweverA 63-year-old 6 ft, 101 kg male with a long-standing history of dyspnea, hypertension, atrial fibrillation, and gout presented with worsening of shortness of breath, fatigue, and lower extremities edema concerning heart failure. Patient was on apixaban 2.5 mg, furosemide 40 mg, lisinopril 2.5 mg and bumetanide 2 mg.On echocardiography, the left ventricle was normal in size (4.2 cm). The ejection fraction was estimated to be 40% and there was diffuse moderate hypokinesis. Wall thickness was moderate to markedly increased. There was moderate concentric hypertrophy. Diastolic features were consistent with a pseudonormal left ventricular filling pattern, with concomitant abnormal relaxation and increased filling pressure suggestive of grade 2 diastolic dysfunction. Right ventricle size and systolic function were normal. There was mild mitral regurgitation and the left atrium was markedly dilated. The transaortic, trans pulmonic, and trans tricuspid velocities were within the normal range with no evidence of stenosis or regurgitation. The tricuspid jet envelope definition was inadequate for the estimation of RV systolic pressure. The inferior vena cava was normal in size and respirophasic changes were normal. There was no pericardial effusion. The left atrial diameter was 4.5 cm, interventricular septal diameter 1.7 cm, left ventricular internal end-diastolic diameter 4.4 cm, left ventricular internal diameter end systole 3.1 cm, and left ventricular posterior wall end diastole 1.7 cm. There was markedly reduced peak global longitudinal strain at - 5.8% with a homogeneous reduction in deformation across all left ventricular myocardial segments with apical sparring.Serum and urine electrophoresis were negative for monoclonal immunoglobulin. Urine electrophoresis showed proteins < 5 mg/dl. Specific M-protein could not be identified on serum immunofixation. Serum immunoglobulin kappa free light chain was 1.91 , lambda free light chain 2.59 , and K/L ratio 0.74 . The patient was consulted by hematology and a bone marrow biopsy demonstrated normocellular marrow with trilineage hematopoiesis and no increased plasma cells.CMR showed characteristic CA findings as explained in the figure legends Figures , 2.The scintigraphy acquired one hour after an injection of 795.5 MegaBequerel (21.5 milliCurie) 99mTc-PYP showed specific features as described in the figure legends Figure .Single photon emission computed tomography (SPECT) confirmed the uptake is in the myocardium, not the blood pool Figure .Positive CMR and pyrophosphate (PYP) imaging with negative light chains were highly suggestive of ATTR-CA. ATTR-CA is further classified as wild-type ATTR (ATTRwt) and hereditary or variant-type ATTR (ATTRv) based on the TTR gene sequence . AlthougEchocardiographic findings which provide clues to the diagnosis of cardiac amyloidosis include increased left ventricular thickness, grade 2 or more diastolic dysfunction, and decreased left ventricular global longitudinal strain. Characteristic cardiac magnetic resonance imaging findings include diffuse subendocardial or transmural late gadolinium enhancement and abnormal gadolinium kinetics ,6.On delayed post-contrast T1 scout images of CMR, the normal temporal nulling  is classified as type 1 which follows an orderly pattern. Abnormal nulling patterns are types 2, 3, or 4, associated with a higher risk of CA (Table In the presence of typical findings on echocardiography and CMR and with the absence of histology and absent monoclonal gammopathy, a Tc-99m PYP scan can help to further evaluate for ATTR-CA. PYP scintigraphy is acquired in anterior projection one-hour post-injection of the tracer. A qualitative visual evaluation comparing cardiac to rib uptake is graded as grades 0, 1, 2, and 3 (Table Cardiac amyloidosis is a major cause of morbidity and mortality. If histological confirmation is not feasible and there are predictable findings of amyloidosis on echocardiogram and CMR, ATTR-CA is diagnosed by characteristic patterns on PYP scan when monoclonal gammopathy is excluded. Cardiac or extracardiac biopsy with amyloid typing is necessary when monoclonal protein is present. Cardiac transplantation does benefit some patients. Emerging therapies that inhibit amyloidogenic misfolding of TTR are promising. Our patient had typical representative findings of CA on CMR and 99mTc-PYP scan and is now considered for therapy with a transthyretin kinetic stabilizer.


Cardiogenic shock and cardiac arrest contribute pre-dominantly to mortality in acute cardiovascular care. Here, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as an established therapeutic option for patients suffering from these life-threatening entities. VA-ECMO provides temporary circulatory support until causative treatments are effective and enables recovery or serves as a bridging strategy to surgical ventricular assist devices, heart transplantation or decision-making. However, in-hospital mortality rate in this treatment population is still around 60%. In the recently published ARREST trial, VA-ECMO treatment lowered mortality rate in patients with ongoing cardiac arrest due to therapy refractory ventricular fibrillation compared to standard advanced cardiac life support in selected patients. Whether VA-ECMO can reduce mortality compared to standard of care in cardiogenic shock has to be evaluated in the ongoing prospective randomized studies EURO-SHOCK (NCT03813134) and ECLS-SHOCK (NCT03637205). As an innate drawback of VA-ECMO treatment, the retrograde aortic flow could lead to an elevation of left ventricular (LV) afterload, increase in LV filling pressure, mitral regurgitation, and elevated left atrial pressure. This may compromise myocardial function and recovery, pulmonary hemodynamics—possibly with concomitant pulmonary congestion and even lung failure—and contribute to poor outcomes in a relevant proportion of treated patients. To overcome these detrimental effects, a multitude of venting strategies are currently engaged for both preventive and emergent unloading. This review aims to provide a comprehensive and structured synopsis of existing venting modalities and their specific hemodynamic characteristics. We discuss in detail the available data on outcome categories and complication rates related to the respective venting option.The online version contains supplementary material available at 10.1007/s00392-022-02069-0. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as an established therapeutic option for patients suffering from severe cardiogenic shock and/or cardiac arrest , 2. NowaThe original concept of VA-ECMO relies on venous drainage from the right atrium (RA) and retrograde arterial return towards the aortic valve for temporary circulatory support serving as a bridge to myocardial recovery, durable mechanical circulatory support (MCS), transplantation, or refined decision-making based on the patient's overall prognosis . As an iThere are fundamental differences in left and right heart adaptation to increased afterload depending on the underlying etiology and chronic preconditions. In general, derivative hemodynamic implications are based on a factitiously high trans-aortic pressure gradient. Assuming, that LV function is preserved, the first coping mechanism is an increase in LV end-diastolic pressure (LVEDP) and consequently elevated calcium sensitivity and contractile power . Albeit In a large proportion of cases, cardiac function is impaired at baseline and the abovementioned system becomes fragile at best. If LV function deteriorates, the demand for increased oxygen need and sufficient endorgan perfusion is not met. Titrating VA-ECMO flow to the lowest acceptable level as well as careful fluid management using diuretics, hemodialysis, or continuous veno-venous hemofiltration (CVVH) may support this state of left heart decompression. Of course, this is not possible in most severe cardiogenic shock patients accompanying completely collapsed LV-function. As one consequence, higher VA-ECMO flow rates are unavoidable, LVEDP rises, and the LV progressively distends. LV volume overload is particularly grave in case of pre-existing aortic valve insufficiency and competent mitral valve. In contrast, in patients suffering from relevant mitral regurgitation, e.g., resulting from chronic dilated cardiomyopathy, the latter can serve as an outlet for elevated LV pressures at the cost of LA and pulmonary congestion. The resulting increase in pulmonary capillary wedge pressure (PCWP) and pulmonary arterial pressure (PAP) facilitates pulmonary congestion and – in a worst-case scenario – causes lung failure. Additionally, if the VA-ECMO sustained aortic mean arterial pressure cannot be overcome by LV systolic pressure, the aortic valve may not open with every beat . Blood sConsidering the abovementioned impact of increased afterload and the heterogeneity of the underlying cardiac and/or systemic pathologies, the selection of a tailored venting strategy is a key challenge of successful individualized VA-ECMO support. Addressing the Achilles heel of retrograde aortic flow, different venting options are available and could be promising modifications of VA-ECMO treatment. However, currently there are several approaches that are not systematically applied, and its impact are often insufficiently understood . In the Active drainage from the PA during VA-ECMO support reduces circulating blood volume in the pulmonary vascular system, thus reducing LA volume and LV preload. The PA can be accessed percutaneously or surgically via the internal jugular or femoral vein. Integrating PA venting into a VA-ECMO setup can be performed by adding a PA cannula to a separate RA venous drain (= PaVA-ECMO), by using a PA cannula as singular venous drainage (= PaVA-ECMO), or by a multihole tip  or double-lumen cannula  for simultaneous RA and PA drainage. In each case, fluoroscopic and echocardiographic guidance assures correct positioning. Cannulation of the PA can be advantageous if degenerating right heart function or recovering LV function require an adaptation of extracorporeal circulatory support. By inversing PA flow in a PaVA-ECMO configuration, the circuit can be modified quickly at bedside into a right heart assist device or VAPa-ECMO configuration with the very short necessity of stopping ECMO flow. In this type of cannulation, the arterial outflow is divided, with one part towards the aorta and one part towards the PA, enabling a relevant proportion of blood bypassing the compromised RV in an antegrade direction and filling the LV with oxygenated blood , 13.n = 8), who received VA-ECMO and PA venting mostly for acute myocardial infarction (AMI) (37.5%) and myocarditis (25%) . St. St21]. Of note, the TandemHeart  may represent another option for active LA venting. The TandemHeart is a paracorporeal ventricular assist device with an inflow cannula draining blood from the LA and the outflow cannula pumping blood into the aorta via a femoral access point. Transvenous insertion of the 21Fr LA drain is performed percutaneously via the RA and the interatrial septum. The external pump provides flow rates of up to 5.0 l/min which is returned retrograde into the femoral artery through a 15Fr or 17Fr outflow cannula. By active LA draining, the system reduces LV preload and may therefore be an effective venting option. As an alternative product, the REVAS cannula  can also be used for active LA relief. This cannula is available in sizes 18/20/22 Fr and can be used with all VA-ECMO systems. Upgrade of the TandemHeart circuit with an in-line oxygenator as well as combination of the TandemHeart LA drainage cannula in conjunction with VA-ECMO are possible but more demanding . To the n = 124) on outcomes with active percutaneous LA venting compared to patients with an arterial pulse pressure of < 10 mmHg who were treated with isolated VA-ECMO [p = 0.012) and lower—albeit not significant—in-hospital mortality . Additionally, patients with decompression had a higher median duration of VA-ECMO treatment . In a 1:1 propensity score-matched analysis by Alghanem et al. comparing n = 21 patients undergoing VA-ECMO support with active or passive LA venting to n = 21 VA-ECMO alone controls, in-hospital mortality was unaffected , whereas both the length of hospitalization and ICU stay were significantly longer with decompression  [n = 70) did not show significantly improved survival to discharge or higher weaning rate with decompression , considering substantial differences in baseline variables including age and shock etiology [In 2021, Kim et al. published the first controlled retrospective trial ( VA-ECMO  (Table 2ctively) . Anotheretiology . In two etiology , 29.Tabl2 vs. 6Fr/m2 indexed to body surface area, p < 0.05). In two larger cohorts, LA pressure decreases by 10 mmHg  [p = 0.002) [n = 1), as well [A case series by Aiyagari et al. including seven pediatric patients with VA-ECMO support and percutaneous LA venting via transseptal cannulation reported an in-hospital mortality rate of 57%, but echocardiographic improvement of LA dilation after decompression in 71% . Notably= 0.022)  and 7 mm= 0.002) , respect as well . Other c as well , 33. As  as well , 34, 35.n = 50) on therapeutic  vs. prophylactic LA venting using surgical and percutaneous techniques, Na et al. found a reduced 30-day mortality rate with prophylactic decompression . However, this effect did not reach significance at 90 days . On the contrary, Zampi et al. found no difference in survival rates of 137 pediatric patients comparing early  and late (> 18 h) decompression, but longer VA-ECMO treatment duration and ICU length of stay in the late decompression group  [n = 49) [p = 0.013). However, survival to discharge was not affected (p = 0.4).Three larger studies have focused on the timing of LA venting initiation in adult and pediatric cohorts. In a comparative analysis , one patient experienced cardiac tamponade after the procedure [Although Kim et al. and Ok et al. did not observe significant differences in complication rates between venting and control groups  family for left heart support currently comprises the Impella 2.5 , Impella Cardiac Power (CP and CP Smart Assist)  and Impella 5.0 and 5.5 Smart Assist . The first two models are inserted through the femoral or axillary artery and advanced retrograde into the LV under fluoroscopic and echocardiographic guidance. The latter two, the Impella 5.0 and 5.5 require surgical transfemoral, transaxillary, or transubclavian placement, the latter based on a right axillary artery conduit system . The comp = 0.044), a trend towards increased LVEF  and an increase in mean arterial pressure (MAP) . Fumagalli et al. observed a noticeable decrease in PCWP (40 mmHg vs. 7 mmHg) and CVP (11 mmHg vs. 3 mmHg) after LV drainage with a 17 Fr pediatric pigtail in a 34-year-old male patient [Historically, retrograde insertion of a pigtail catheter into the LV was the first percutaneous strategy used for active LV venting Fig. . Since p patient . And eve patient . In anotThe insertion of a pigtail catheter into the LV is an easy and extremely low-cost venting approach which might even be possible to be established at bedside under echocardiographic control. Since this technique is frequently used for diagnostic purposes in catheterization laboratories it might be considered as a low-risk procedure. However, at present there are neither large retrospective data or matched comparisons nor clear evidence showing a mortality benefit, although this method may alleviate LV distension and pulmonary congestion. Furthermore, the maximum venting flow rates are clearly limited by catheter size, which has been demonstrated in an artificial VA-ECMO model . If thisn = 255 patients undergoing ECMELLA compared to n = 255 patients treated with VA-ECMO alone, Schrage et al. found ECMELLA-treatment to be associated with a significantly lower 30-day mortality rate  [p = 0.03) [p = 0.04 and 48% vs. 28%, p = 0.047, respectively) [p = 0.913 for mortality) [The ECMELLA approach—also called ECPELLA—used as a percutaneous decompression strategy Fig.  has been = 0.03) . Early L = 0.03) . Anotherctively) . Not allrtality) . But owip < 0.0001) and increased MAP , but also elevated end-tidal CO2  and pulmonary arterial velocity time integral (PAVTI), evidencing improved pulmonary vascular compliance . Aside from these data, other authors reported decreased PCWP [An elaborated hemodynamic study of 27 patients undergoing ECMELLA treatment by Eliet et al. provided evidence on how an Impella device is contributing to LV decompression . The autsed PCWP , decreassed PCWP , reductised PCWP , as wellsed PCWP  after Imsed PCWP .p < 0.01, 38% vs. 29%, p = 0.6, respectively) highlighting the invasiveness of this approach [p < 0.01) [p = 0.01) [p = 0.002) [p = 0.004) [Impella devices are contraindicated in presence of LV thrombus, mechanical aortic valve prosthesis, moderate to severe aortic valve disease, and severe peripheral artery disease, which limits its use for critically ill patients. But even for eligible patients, Impella insertion may entail serious risks. Schrage et al. and Pappalardo et al. observed higher rates of major bleeding in the ECMELLA group compared to matched controls   in diffe < 0.01) , 58, 59. = 0.01) , Akanni = 0.002) , and Pap= 0.004) . Recent = 0.004) , 61. In = 0.004) , 53 and = 0.004) .Large retrospective multicenter studies have shown that the ECMELLA concept may translate into survival benefit, despite the indisputable risk of hemolysis, as well as higher bleeding and access site complication rates. In this regard, the 1:1 propensity-matched analysis by Schrage et al. is by now the best available evidence of its effectiveness . To overHemolysis is a serious adverse event, which can even require withdrawal of Impella support. In the first-in-man case report presented by Tschöpe et al. in 2020, replacement of an Impella CP with the PulseCath iVAC 2L pulsatile device was performed when laboratory assessment displayed persistent signs of hemolysis 6 days after ECMELLA initiation  Table 33. CardioTwo older case reports have shown effective LV unloading with a surgically implanted 20Fr cannula , 59 Tab. The firp < 0.01). Surgical LV decompression was associated with lower mortality during support  as well as 30-day mortality , although Kaplan–Meier-estimates of long-term survival did not show significant benefit after 6 and 12 months. Furthermore, the median duration of VA-ECMO support was longer in the LV venting group . In another smaller cohort including 12 VA-ECMO treated patients with simultaneous decompression the overall mortality rate was 41.7% [n = 8) in-hospital mortality rate was 25% and successful weaning rate was 87.5% [Further clinical data on surgical LV venting have been published by Schmack et al., who retrospectively evaluated 48 VA-ECMO runs from 2004 to 2014 . Of all as 41.7% . The tecas 87.5% . In singas 87.5% , 65, LV as 87.5% , reopenias 87.5% . Of noteas 87.5%  and one as 87.5% . Overallas 87.5% . In mostSurgical techniques allow for large bore LV cannulation and effective LV decompression. Despite surgical trauma and its potential complications there may be signals toward short-term survival benefits based on retrospective data. However, the data on surgical venting options are particularly scarce regarding outcomes and safety and sufficiently powered RCTs are urgently needed but might never be performed.n = 533) compared to VA-ECMO alone (n = 533)  [p < 0.001). Last, the VA-ECMO weaning rate was higher in the IABP group . In another propensity-matched analysis by Bréchot et al., decompression with an IABP led to a trend towards improved ICU-mortality, but did not reach significance  [p < 0.0001). In line with this, Tepper et al. found a reduced, but not significantly lower, 30-day mortality rate in their cohort of 60 patients suffering from post-cardiotomy shock when comparing patients undergoing VA-ECMO treatment with and without IABP  [n = 529), but significant differences in baseline characteristics between the VA-ECMO alone and combined treatment group may have strongly influenced this result [The IABP reduces LV afterload by pulse-synchronous systolic negative pressure generation through deflation of a helium-filled balloon and improves coronary and bypass graft perfusion, when the balloon is inflated in diastole , 67. Thectively) . A subgr = 0.06) . Additio = 0.06) . The VA-s result .Table 4Ap = 0.031).Regarding the timing of IABP initiation, Gass et al. evaluated the outcomes of 137 patients, 41% of which received IABP before VA-ECMO initiation compared to controls with delayed IABP insertion . Prior Ip = 0.003), mPAP , and PCWP  after IABP re-start. Tepper et al. found CVP to be significantly decreased 48 h after VA-ECMO initiation only in the IABP group  [The hemodynamic effects of IABP during VA-ECMO were analyzed in detail by Petroni et al. . In thei = 0.01) . Interes = 0.01) . Of the  = 0.01) .p = 0.012) [Complications related to IABP reported by Bréchot et al. include access site bleeding in 14%, access site infection in 1%, minor distal ischemia in 5%, and device dysfunction in 3% . Bonacch= 0.012) . Overall= 0.012) , 71, 76.= 0.012) .Taken together, the published data on IABP as an active, indirect LV venting option suggest a survival benefit at a relatively low risk of device-related complications and low-cost. Furthermore, IABP can even be implanted at bedside on ICU guided by echocardiography and followed by chest X-ray for positioning. Another advantage of the IABP is the lack of some contraindications which are inherent to active LV-venting devices— most importantly here the LV-thrombus. The latter is of relevance since the most frequent reason for cardiogenic shock is anterior STEMI bearing the greatest risk of LV thrombus formation. These points might be reasons that the IABP is still the most often used venting device outside Germany. Currently, evidence for IABP is even stronger—in terms of the availability of larger matched retrospective trials—compared to the evidence existing for ECMELLA strategy. The latter, however, is much more expensive and associated with a higher complication rate. Like for many other previously described venting strategies, the lack of prospective data calls for future RCTs to evaluate mortality and complication rates as well as to improve implantation timing and therapeutic management of IABP as venting strategy during VA-ECMO support.Passive atrial venting strategies are based on a volume shift from overloaded LA into RA through an interatrial septum defect. In theory, an iatrogenic left-to-right shunt as an “overflow valve” for the LA aims to reduce LV preload and distension. Interseptal atrial communication may be achieved by percutaneous transvenous septostomy, balloon dilation, or stent implantation Fig. . For tran = 15) was 46.7% [p = 0.017). The large number of emergency procures may explain the difference to the study by O’Byrne et al., who reported—with a median interval of VA-ECMO initiation to decompression of 0 days—a much lower in-hospital mortality rate of 18% [To date, data regarding outcomes are only available from retrospective observational studies without any control groups Table . The in-as 46.7% . Prasad as 46.7% . In a mias 46.7% . In the as 46.7% . Notablye of 18% .Table 5Pp < 0.0001) and LA to RA pressure gradient after decompression  [p < 0.0001 and − 11 mmHg, p = 0.001, respectively) [2/FiO2 ratio improved from baseline to 24 h after decompression (p = 0.002) [Hemodynamic data from three of the abovementioned studies can serve as a proof on concept for passive atrial venting. Thus, O’Byrne et al. found a significant reduction of LA pressure  . Baruteactively) , 82. In = 0.002) , 82.Inherently, persisting atrial communication after passive atrial venting is a frequently noticed long-term complication in patients who survived VA-ECMO therapy and did not undergo heart transplantation. Transcatheter or surgical closure may be performed at a later stage, or if durable LVAD implantation requires open heart surgery –80. An iAlthough passive atrial venting may enable effective decompression during VA-ECMO support, mortality and safety outcomes compared to controls have not been investigated, not to mention that there are no RCTs available yet. Obviously, a comparison of the active and passive LA decompression approach would be of particular interest. Due to the frequent use of this technique in children, most data derive from this subgroup and results cannot automatically be transferred to the adult population. The crude data on LA pressure pre and post cannulation or septostomy suggest, that both methods are capable of reducing pressure by ~ 10–15 mmHg. Overall, there are currently no data available to support one of these two options as superior venting strategy in patients undergoing VA-ECMO treatment.n = 16) showed a greater reduction of LA diameter, PCWP, and sPAP than IABP (n = 20) or percutaneous balloon septostomy (n = 17) (p = 0.001) [p = 0.783) and in-hospital mortality rates (p = 0.783) did not differ between groups, which may be related to higher rates of procedure-related complications in the surgical venting group, including bleeding, ventricular arrhythmias, cannula thrombosis, and malpositioning.In a recent retrospective study comparing three different venting strategies by Hasde et al., transapical LV cannulation (= 0.001)  Table 6n = 16 shp = 0.038) and trans-apical cannulation  were both independent predictors of early mortality.In a large prospective multicenter cohort of 209 post-cardiotomy shock patients published by Bonacchi et al., all patients without pre-operative IABP insertion were upgraded at the time of VA-ECMO initiation, while 74.2% of the patients additionally received a trans-apical (50.3%) or transpulmonary (49.7%) venting cannula for refractory pulmonary edema or insufficient LV decompression . Intraopp = 0.49), but only Impella-treated patients surpassed the predicted mortality calculated by the SAVE-Score (37% vs. 18%). Considering that Impella-treated patients were significantly older  and 25% of the patients in the IABP group required additional LV venting, the majority of patients in each group received LV decompression simultaneously with VA-ECMO initiation. The rate of major complications including hemolysis (p = 0.70), bleeding (p = 0.15), vascular complications (p = 1), ischemic stroke (p = 0.42), and intracardiac thrombus (p = 0.46) were not different between the groups. The authors also evaluated outcomes with respect to the timing of venting initiation. Patients, who received immediate/preventive LV venting, had a similar chance of survival to 30 days compared to patients with reactive LV venting (p = 0.46). However, baseline age was significantly higher in the immediate venting group.Piechura et al. retrospectively analyzed Impella CP and IABP for LV decompression in 63 VA-ECMO patients (non-matched) . 30-day n = 23, Impella 2.5, CP, or 5.0) or surgically implanted LV vent  [p = 0.02 and 20 mmHg vs. 15 mmHg, p = 0.01, respectively). Signs of pulmonary edema improved in 65% and 25%, respectively, but 30-day survival rates were not significantly different .In 2017, Tepper et al. evaluated 45 VA-ECMO runs with concomitant LV venting using Impella  . The maiCurrently, two large, randomized trials EURO-SHOCK and ECLS-SHOCK are recruiting patients to answer the question if VA-ECMO therapy in cardiogenic shock improves survival. Both trials will not answer the question whether or not concomitant venting is needed. Hence, adequately powered, prospective RCTs on LV venting strategies will not be available in the upcoming years. However, data gained during the past years have certainly given intensivists a better understanding of the hemodynamics, outcomes, and adverse effects of different venting strategies for patients undergoing VA-ECMO support. Modifications of the basic VA-ECMO circuit and novel devices for LV unloading have added to the complexity of patient management. There is expert consensus that venting should be considered, if aortic flow is non-pulsatile, progressive signs of LA or LV distension, elevated PAP or PCWP, radiographical signs of pulmonary congestion, persistent closure of the aortic valve, or intracavitary blood stasis are detected. Individual patient characteristics, including previous cardiac surgery, vascular preconditions, bleeding risk and presence of LV-thrombus and overall prognosis, should guide the Heart Team’s decision making which decompression method may be the most promising. The classification system of venting techniques, offered in the present review, may be utilized in clinical practice and as a framework for future research. The Heart Team in dedicated high-volume ECMO centers should aim at conducting pioneering RCTs comparing VA-ECMO support with vs. without venting strategies with the currently best investigated strategies active LV-unloading or IABP, to close this massive gap of evidence. Then, remaining questions will still be the timing of venting (immediately or by advent of a distinct condition) and if venting is necessary or beneficial in all patients undergoing VA-ECMO treatment.Supplementary file1 (DOCX 22 kb)Below is the link to the electronic supplementary material.


Moreover, RVT2 was positively correlated with CI and negatively correlated with mPAP and PVR before  and after BPA . Conclusion: Ventricular blood pool T2 mapping might be novel non-invasive CMR imaging marker for assessment of disease severity, prognosis, follow-up and even therapy monitoring in PH.Background: Parametric imaging has taken a steep rise in recent years and non-cardiac applications are of increasing interest. Therefore, the aim of our study was to assess right (RV) and left ventricular (LV) blood pool T1 and T2 values in patients with chronic thromboembolic pulmonary hypertension (CTEPH) compared to control subjects and their correlation to pulmonary hemodynamic. Methods: 26 patients with CTEPH , who underwent CMR and right heart catheterization (RHC) before and 6-months after balloon pulmonary angioplasty (BPA), were retrospectively included. Ventricular blood pool values were measured, compared to control subjects  and correlated to invasive measures . Results: In both, control subjects and CTEPH patients, RVT1 and RVT2 were significantly reduced compared to LVT1 and LVT2. Compared to control subjects, RVT2 was significantly reduced in CTEPH patients ( Due to the outstanding success of parametric imaging techniques in the diagnosis of various cardiac diseases, parametric imaging—native T1 and T2 mapping and also quantification of extracellular volume (ECV)—has already found its way into diagnostic recommendations ,5,6,7,8.In addition to purely cardiac fields of application, non-cardiac tissues are also increasingly being examined by parametric imaging. For example, a very recent study by Guo et al. investigated the value of hepatic T1 mapping in patients with PH and demonstrated, that hepatic T1 values were predictive for adverse cardiovascular events . FurtherIn particular, the approach to investigate native T1 and T2 blood pool values and ratios is completely new and seems very interesting, because previous studies have shown that blood T2 is sensitive to the level of blood oxygenation and quantitative T2 Mapping as a novel, non-invasive method enables estimation of blood oxygen saturation ,13. SincA total of 26 consecutive CTEPH patients ) were included in this retrospective cohort study from February 2014 to September 2017. To reduce contrast media and magnetic field risks for healthy volunteers, the first 26 patients , who had undergone cardiac MRI for exclusion of myocardial inflammation between October 2022 and December 2022, were selected as control subjects. The control subjects were only included in the control group if both cardiac MRI examination and patient follow-up were completely unremarkable . Exclusion criteria and contraindications for CMR examinations were: kidney failure, incompatible metal or cochlear implants, known gadolinium intolerance and claustrophobia.Imaging was performed on a 1.5 Tesla MRI system  using a six-element phased array cardiac coil. The standardized imaging protocol comprised localizers, CINE imaging/steady-state free precession sequences (SSFP) in long-axis , and short-axis (SA) orientation, late gadolinium enhancement imaging (LGE), and parametric imaging with native T1 and T2 mapping. LGE imaging was performed 12 min after contrast media injection 2; matrix 192 × 124; flip angle 35°; TR 740 ms and TE 1.06 ms; TI 100 ms and TI increment 80 ms; trigger delay 300 ms; inversions 3; acquisition heartbeats 3,3,5—11 images were acquired during 17 heartbeats.T1 mapping was performed as an optimized modified Look–Locker inversion–recovery  sequence was used. After performing of in-line motion correction, three T1 maps were acquired . Imaging parameters were as follows: slice thickness 8 mm; spatial resolution 2.2 × 1.8 × 8 mm; 6/8 partial Fourier acquisition; field of view (FOV) 240 × 340 mm2 to 325 × 400 mm2 depending on heart rate; matrix 104 × 160; bandwidth 947 Hz/pixel; acceleration factor 2. T2 mapping was performed as a standardized T2-prepared SSFP single-shot sequence, as previously described . A nonri2 and the upper limit as 300 mm2 to guarantee comparable and valid measurements for all CTEPH patients and controls. LV and RV native T1 and T2 blood pool values were measured in regions of interest (ROI) at the basal or midventricular SA section. All ROIs were drawn carefully within the LV and RV to avoid measuring of partial volume-averaging artefacts and registration errors with gradual T1 changes at myocardial borders, due to including of trabeculae and papillary muscles. The lower limit of the measured blood pool ROI areas was defined as 100 mmThe T1 and T2 measurements were performed by two board-certified and experienced radiologists , and all T1 and T2 maps were of diagnostic quality (no patient had to be excluded). Both investigators were blinded to the patient demographics. At baseline, the first investigator performed all native T1 and T2 blood pool measurements and repeated the measurements after 14 days to assess intraobserver variability. The second investigator performed all native T1 and T2 blood pool measurements to determine interobserver variabilities. Postprocessing was performed by using the cardiovascular imaging software version 42 .Standardized RHC was performed in all patients via the right internal jugular vein (6F sheath and standard Swan-Ganz catheter) within the pre- and postprocedural  diagnostic workup. t-test was used, and for not-normally distributed data, the Wilcoxon signed-rank test (non-parametric) was applied. The correlation strengths were tested using the Spearman correlation coefficient r and interpreted according to Hinkle et al. [The statistical analyses were obtained by using PRISM statistical software . Patient characteristics were expressed by mean ± SD. All data were checked for normal distribution using the Shapiro–Wilk test. In cases of normally distributed data, Student’s e et al. . Accordip = 0.0063 and p < 0.0001) and control subjects (p = 0.0002 and p < 0.0001). p = 0.0065), whereas LVT2, RVT1 and LVT1 differed not significantly compared to control subjects. In contrast to RVT1/LVT1, RVT2/LVT2 differed also significantly between CTEPH patients and control subjects (p = 0.0006). p = 0.0048 and p = 0.0036), whereas LVT2, RVT1, LVT1 and RVT1/LVT1 differed not significantly after BPA. p = 0.007) and a significant positive weak correlation after BPA . Moreover, RVT2 also showed significant negative weak correlations to PVR before  and after BPA , whereas only non-significant weak correlations to mPAP before  and after  BPA were present. Interestingly, RVT2 showed a significant positive moderate correlation to CI before BPA  and control subjects  were very low.The intra- and inter-observer variabilities in CTEPH patients LV and RV native T1 and T2 blood pool values measured on basal SA sections are reproducibly in both control subjects and CTEPH patients.(2)RVT1 and RVT2 values are lower compared to LVT1 and LVT2 values in both control subjects and CTEPH patients.(3)Moreover, RVT2 blood pool values are significantly reduced compared to control subjects in CTEPH patients, whereas LVT2 blood pool values are similar.(4)Interestingly, RVT2 blood pool values show significant correlations to measures of pulmonary hemodynamic (mPAP and PVR) and correlates of oxygen saturation (CI) before and even after BPA.The four most significant findings of our study are: To explain and understand these results, one needs to understand pathophysiological and technical MRI aspects. Relaxation times of blood are a function of hemoglobin quantity and oxygen saturation ,25 and tIn healthy people, the arterial oxygen saturation in the left heart is higher than the venous oxygen saturation in the right heart. This is concordant to our finding that LVT2 blood values are higher than RVT2 blood values in both control subjects and CTEPH patients. Compared to the control subjects, the RVT2 blood values are significantly decreased in CTEPH patients. This can be explained by the lower blood oxygen saturation and increased deoxyhemoglobin due to the increased PVR and right heart failure in patients with PH. Compared to that, the oxygen saturation in the left ventricle seems not affected as LVT2 blood values are similar between CTEPH patients and control subjects, again very well fitting to the pathophysiology of precapillary PH. Furthermore, RVT2 blood values were significantly positive correlated to CI and significantly negative correlated to PVR before and after BPA, whereas a weak not significant negative correlation to mPAP was present. These correlations impressively demonstrate that therapy-associated improvements in mPAP, PVR, and oxygen saturation are accompanied by concomitant changes in T2 values. At least, blood pool T1 mapping seem less affected by changes of oxygen saturation as they do not significantly differ between the CTEPH patients and the control subjects. This is in line with results presented by Lin et al., who showed that blood T1 times were independent of oxygen saturation . The sliThe main limitations of this study are: First, it was a single-centre study with a relatively small number of included patients. Second, our study only included CTEPH patients and, therefore, only limited inferences on blood pool T2 values, oxygen saturation and pulmonary hemodynamic in other PH subgroups appear to be permissible. Third, postcontrast mapping, which might provide additional information, was not a subject of this study. Fourth, hemodynamic of the control subjects is not eligible as RHC is not obtained in healthy people. Fifth, hematocrit values, which also affect the measured native T1 and T2 blood pool times beside oxygenation, were not assessed.Based on our results, we conclude that right ventricular blood pool T2 mapping might be a novel and additional non-invasive CMR imaging marker and increment for assessment of disease severity, prognosis, follow-up and even therapy monitoring in PH.