As a novel physiological pacing technique, left bundle branch pacing (LBBP) can preserve the left ventricular (LV) electrical and mechanical synchronization by directly capturing left bundle branch (LBB). Approximately 60–90% of LBBP were confirmed to have captured LBB during implantation, implying that up to one-third of LBBP is actually left ventricular septal pacing (LVSP). LBB capture is critical for distinguishing LBBP from LVSP.A total of 15 articles were included in the analysis by searching PubMed, EMBASE, Web of Science, and the Cochrane Library database till August 2022. Comparisons of paced QRS duration between LVSP and LBBP have not been uniformly concluded, but the stimulus artifact to LV activation time in lead V5 or V6 (Stim-LVAT) was shorter in LBBP than LVSP in all studies. Stim-LVAT was used to determine LBB capture with a sensitivity of 76–95.2% and specificity of 78.8–100%, which varied across patient populations.The output-dependent QRS transition from non-selective LBBP to selective LBBP or LVSP is direct evidence of LBB capture. LBB potential combined with short Stim-LVAT can predict LBB capture better. Personalized criteria rather than a fixed value of Stim-LVAT are necessary to confirm LBB capture in different populations, especially in patients with LBB block or heart failure. LBBP catraction .via a trans-ventricular septal approach to LV septum, and both of them can produce relatively narrow paced QRS duration and continuously dynamic changes of paced QRS morphology from left bundle branch block (LBBB) to right bundle branch block (RBBB) pattern. LVSP, on the other hand, is fairly straightforward because there is no need to confirm the LBB capture by recording of LBB or His bundle potential, accurate initial pacing localization on fluoroscopy, or extra pacing maneuvers (The implantation process of LBBP and LVSP is similar in that both of them are advanced from right ventricular (RV) septum aneuvers , 4. Appraneuvers , 6. Curraneuvers , 6, 7. IElectronic databases, including PubMed, EMBASE, Web of Science, and the Cochrane Library database were comprehensively searched (until August 2022) to identify primary references using the terms of (1) “left bundle branch pacing” OR “left bundle branch area pacing” and (2) “left ventricular septal pacing.” We excluded animal studies, abstracts, reviews, editorial and individual case reports. References from the relevant articles were reviewed and related articles were identified. A total of 15 articles were selected for detailed review –17 Tabl.Back in 1970, Durrer et al. measured the total excitatory process of seven isolated normal human hearts by as many as 870 intramural terminals . Within P = 0.02 and 0.004, respectively)  patients with normal cardiac structure and found that LVSP had an immediate effect on LV hemodynamics comparable to atrial pacing and superior to RV apex pacing (RVAP) and RV septal pacing (RVSP) (ctively) .LBB, originating in branching portion of the His bundle located underneath the junction of the non-coronary cusp and the right coronary cusp of the aortic valve, distributed in a broad ribbon-like structure in the LV septal sub-endocardium , 23. LBBLBBP has electrophysiological advantages over HBP in addition to anatomical advantages. According to the longitudinal dissociation theory, LBB and RBB have been predominantly separated by the insulated fiber sheath inside His bundle , 24, 25.In 2017, Huang et al. performed LBBP on a patient with dilated cardiomyopathy and heart failure whose LBBB was not corrected by HBP. The typical LBBB with QRS duration of 180 ms was corrected by LBBP beyond the conduction block with a low pacing output, and then the accompanying RBBB morphology was eliminated by adjusting the atrioventricular delay . A numbeIn theory, LBBP rapidly conducts electrical excitation through the intrinsic His-Purkinje system, accelerating the process of LV lateral wall depolarization while comparatively delaying the RV excitation, resulting in electrical dyssynchrony between the left and right ventricles , 13. LVSP > 0.05), while capturing LBB reduced the Stim-LVAT by about 10 ms or more   (P < 0.001), although paced QRS duration is slightly longer . It should be noted that the Stim-LVAT of LBBP and LVSP in this study were 48.70 ± 13.67 and 58.70 ± 13.67 ms, respectively, which are significantly shorter than those in any other studies (P = 0.138), this study proved that LBBP seems to result in a small, but significant, improvement in ventricular synchrony when compared to LVSP by calculating QRS area using electrocardiography and vectorcardiogram  and Stim-LVAT . The transition from NSLBBP to LVSP resulted in an increase in Stim-LVAT by ≥15 ms (78.4 ± 10.8 vs. 98.4 ± 13.9 ms) but only minimally influenced RWPTV1 . Consequently, during SLBBP, the V6-V1 interval was longest, intermediate during NSLBBP, and shortest during LVSP . The optimal value of V6-V1 interval for distinguishing NSLBBP from LVSP was 33 ms, with a specificity of 90% and a sensitivity of 71.8%, while the V6-V1 interval for confirming the LBB capture was 44 ms, with a specificity of 100%  (Stim-LVAT varies across patient populations and is prolonged in large ventricular size or LBBB in patients with heart failure (HF) , suggestnd LVSP) . The delnd LVSP) . Recentlnd LVSP) . The floThe transition from NSLBBP to SLBBP or LVSP is the gold standard for confirming LBB capture, but it may not be achieved due to similar capture thresholds for LBB and nearby myocardium. In this scenario, the recorded LBB potential combined with short Stim-LVAT can predict LBB capture and ventricular mechanical synchrony better. Personalized criteria, such as ΔStim-LVAT, ΔStim-LVAT%, or comparison of paced LVAT and difference between IDT and TCT, can be utilized to confirm LBB capture in patients with HF or LBBB.KZ: conceptualization and writing—original draft preparation. LL and JL: contribute to our revised draft and provide useful comments. DC and QL: supervision and writing—reviewing and editing. All authors contributed to the article and approved the submitted version.This work was supported by research grant No. 3502Z20214ZD1165 from Xiamen Municipal Bureau of Science and Technology.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Cardiotoxicity may present as (pulmonary) hypertension, acute and chronic coronary syndromes, venous thromboembolism, cardiomyopathies/heart failure, arrhythmia, valvular heart disease, peripheral arterial disease, and myocarditis. Many of these disease entities can be diagnosed by established cardiovascular diagnostic pathways. Nuclear medicine, however, has proven promising in the diagnosis of cardiomyopathies/heart failure, and peri- and myocarditis as well as arterial inflammation. This article first outlines the spectrum of cardiotoxic cancer therapies and the potential side effects. This will be complemented by the definition of cardiotoxicity using non-nuclear cardiovascular imaging  and biomarkers. Available nuclear imaging techniques are then presented and specific suggestions are made for their application and potential role in the diagnosis of cardiotoxicity. The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. This position paper is intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from this position paper, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the position paper when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the position paper. The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognized that adherence to this position paper will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of this position paper is to assist practitioners in achieving this objective. The aim of this article is to review available imaging modalities in nuclear medicine that have been validated or show promise for the assessment and prevention of cancer therapy-related cardiotoxicity (both systemic treatments and radiotherapy). The background of the respective nuclear imaging techniques will be briefly described, and the existing literature reviewed. For the clinical point of view, eligible patients and responsible therapies that cause cardiotoxicity will be summarized. Furthermore, specific application suggestions for nuclear medicine imaging for assessing cardiotoxicity are given. At this point, we would like to point out that, however, this cannot represent a guideline, since there is still not yet sufficient evidence for some of the nuclear medicine applications discussed and these very promising imaging options still need to be validated further.Increased survival rates in cancer patients render cardiovascular side effects of cancer therapies increasingly important for long-term morbidity and mortality. Pre-existing cardiovascular diseases, cardiovascular risk factors, genetic predisposition, previous therapies, and growing patient age are associated with an increasing risk for and may aggravate complications following cancer treatments , 2. ThisArguably, left ventricular dysfunction (cardiomyopathy) and manifest heart failure are the most concerning forms of cardiotoxicity with a profound impact on morbidity and mortality. Heart failure can manifest at an early  or late phase . Anthracycline chemotherapy  induces left ventricular dysfunction in a dose-dependent manner , 6. The As radiotherapy is associated with significant cardiovascular complications, it is important to realize that approximately 35% of cancer patients undergo radiotherapy within 1 year after diagnosis . These lPatients with a predisposition for cardiovascular complications from cancer therapy require standardized cardio-oncological monitoring for an early identification and subsequent treatment of cancer therapy-related side effects . Figure At baseline, the assessment of patients requiring cancer therapy includes the assessment of conventional cardiovascular risk factors and pre-existing cardiovascular disease that may aggravate the risk for cardiovascular toxicities , 14. PreCardio-oncological surveillance during therapy depends on the individual patient’s risk and on the applied therapy. A general cardio-oncology visit includes a clinical examination, ECG, cardiac biomarkers, and echocardiography . Of noteMoreover, other imaging modalities including CMR have been also proposed for the investigation of cancer therapy-related cardiotoxicity . For antGiven its accuracy and reproducibility in LVEF determination, CMR is considered by the American College of Cardiology/American Heart Association (ACC/AHA) as a method to screen for cardiotoxicity in patients undergoing cancer therapy . MoreoveThe long-term follow-up of patients after completion of cancer treatment is driven by the baseline risk factors and therapy-related risk factors. Patients receiving chest radiotherapy are at high risk for late complications, particularly new-onset coronary artery disease, and require long-term follow-up , 2, 23. There are a number of nuclear medicine imaging modalities to detect cardiotoxic damage. The following paragraphs discuss the most commonly used imaging modalities or those with the highest potential from the authors’ perspective. Table 99mTc radiolabeling of patient’s red blood cells (RBCs) [99mTc]Tc-erythrocytes represent the most commonly used radiotracer. There are three methods for RBC labeling , with different labeling efficiency  H2O PET pre- versus post-radiation (2 and 8 months) therapy, a decrease in stress MBF in the majority of cases could be assessed, both considering the global values and the left anterior descending segments. Remarkably, none of the patients had a stress MBF below the diagnostic threshold for coronary artery disease -Metaiodobenzylguanidine ([123I]mIBG) is a radiolabeled guanethidine analog, which is taken up, concentrated, and stored in the presynaptic nerve terminals of the sympathetic nervous system in a manner similar to norepinephrine. The role of the dysfunctional autonomic nervous system regulation in heart failure is well established and myocardial sympathetic imaging with [123I]mIBG now has a range of proven applications in heart failure patients mIBG scintigraphy has not yet found its clinical place in the early identification and monitoring of cancer therapy‐induced cardiotoxicity.Functional and structural injury to myocardial adrenergic neurons may be part of the pathophysiology of cancer therapy-induced cardiotoxicity , 50, and123I]mIBG scintigraphy in 447 subjects. This study strongly emphasizes the need to limit heart irradiation during radiotherapy, particularly for patients with adriamycin treatment.Also the role of radiotherapy in the risk of long-term cardiac disease following childhood cancer treatment is evaluated in the association with systemic therapy , 52. One123I]mIBG imaging in the setting of cardiotoxicity will depend on further investigation in prospective clinical trials, including the application of high sensitive CZT cameras.The fate of [11C]metahydroxyephedrine ([11C]mHED) or other novel promising PET tracers including the 18F-labeled variant [18F]flubrobenguane , a novel cardiac neuronal imaging agent with properties similar to [123I]mIBG mIBG , or the 23I]mIBG .PET/MR hybrid imaging may be of interest, allowing combined regional molecular and functional LV imaging, that could potentially detect subtle myocardial and molecular signal changes as a very early sign of cardiotoxicity .18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET when the patient is adequately prepared .PET allows to image changes in cellular metabolism with high sensitivity and appears therefore well suited to identify earlier stages of cardiomyocyte toxicity, before irreversible myocardial damage develops. It must be distinguished here that, on the one hand, cardiotoxic therapy may cause abnormalities in myocardial glucose metabolism, i.e., in the viability assessment of the heart. On the other hand, a myocardial inflammatory reaction may occur as a result of cancer therapy , which 18F]FDG is taken up by cardiomyocytes through GLUT receptors and then phosphorylated by hexokinase resulting in its intracellular retention. 2-[18F]FDG is therefore well suited to identify the metabolic shift in the myocardium in response to anthracycline treatment. Several retrospective studies [18F]FDG uptake in the myocardium of patients treated by anthracyclines on PET, which was associated with an increased incidence of LV dysfunction during follow-up. The use of 2-[18F]FDG PET for the early identification of cardiotoxicity appears an attractive imaging approach as patients often undergo sequential 2-[18F]FDG PET examinations during the course of their oncological disease. However, increased 2-[18F]FDG uptake is not specific for anthracycline-induced cardiotoxicity as it is also observed in ischemic myocardium or in patients with elevated circulating insulin levels following sugar consumption. Further carefully conducted studies are required to confirm whether the quantification of myocardial 2-[18F]FDG uptake could be a robust early-stage predictor of cardiotoxicity-related LV dysfunction. These studies should be conducted with adequate suppression of cardiac glucose metabolism, as this increases the interpretability of 2-[18F]FDG PET/CT studies. Although no standardized guidelines are available, prolonged fasting (beyond 12 h), carbohydrate-restricted diets, fatty meals, and heparin loading have been proposed [18F]FDG injection. The aim of this protocol is to decrease basal insulin and blood glucose levels and to increase blood free fatty acid (FFA) levels, which shift myocardial energy consumption away from glucose toward FFA. Though the bleeding risk is very low if used properly as a single dose, heparin should be avoided in patients who are already receiving anticoagulant therapy or have a history of bleeding disorders and attention should be paid to tumors at risk of bleeding and brain metastases.Anthracyclines interfere with normal mitochondrial oxidative metabolism causing a shift from lipids to glucose metabolism for energy supply . 2-[18F] studies , 59 haveproposed . A proto111In]In-antimyosin, a murine monoclonal antimyosin Fab antibody fragment. This tracer visualizes cellular necrosis because it binds to intracellular myosin and only if the sarcolemma is damaged. This tracer has been used in several studies to investigate cancer therapy-induced cardiotoxicity [111In]In-antimyosin for prognostic assessment regarding the development of cardiotoxicity-related heart failure. Only limited data are available for imaging radiotherapy-induced cardiotoxicity using this tracer Tc-annexin V, a tracer that has not yet been widely used. In a doxorubicin-induced cardiotoxicity model in the rat, the feasibility of imaging with this tracer was demonstrated FDG. In the beginning of the twenty-first century, the first prospective milestone study in 2-[18F]FDG PET imaging of atherosclerosis was published followed by numerous publications on experimental, clinical, and methodological aspects of this topic [18F]FDG uptake and histologically proven inflammatory changes in arterial specimen, but also with e.g. clinical cardiovascular risk factors as well as with prognostic parameters could be identified FDG PET imaging of atherosclerosis F-flubrobenguane) FDG PET is useful to detect altered metabolism of the myocardium or to detect cardiac inflammatory effects. Imaging of damage of myocardial innervation may also be considered as an early sign of cardiotoxicity. In particular, [68Ga]Ga-FAPI PET appears to be a potential promising application for the future, although this remains to be evaluated in studies. These very sensitive methods should be used when CMR, echocardiography, ERNA, and SPECT show no abnormalities or unclear findings and cardiotoxicity is still suspected. If PET MPI shows a decrease in MBF or MFR, or a new onset of microvascular dysfunction, this is a sign of cardiotoxicity and should lead to a modification of the therapeutic regimen. Similarly, a new abnormality on FDG PET of the heart should lead to a modification of the therapeutic regimen . After completion of therapy, reassessment of cardiac function by ERNA or SPECT MPI is reasonable to detect myocardial damage that has occurred if echocardiography or CMR are not feasible or available. Furthermore, the imaging method selected before the initiation of therapy should be chosen for follow-up for better comparability.Figure 18F]FDG PET also seem to be useful as further diagnostics. 2-[18F]FDG PET can also be used to determine whether increased inflammatory activity in the vessels has occurred as a result of cardiotoxic therapy; however, this represents a future application, as only little data is available and the value should be further investigated. [68Ga]Ga-FAPI PET appears to be a promising future imaging modality to detect cardiotoxic cardiac injury at a very early stage. Also [68Ga]Ga-FAPI PET allows to distinguish between active fibrosis and mature scars. Therefore, [68Ga]Ga-FAPI PET can be considered when conventional imaging modalities have been unremarkable or non-conclusive and cardiotoxicity remains suspected. If cardiotoxic injury is detected, further cardiologic evaluation and initiation of therapy should follow.PET MPI and 2-[The topic of cardiotoxicity is complex. The diagnosis and therapy of a cardiovascular disease due to a previous cancer therapy therefore requires a close interdisciplinary approach including cardiologists, oncologists, radiation therapists, and imaging disciplines (radiology and nuclear medicine), among others. Only this interplay of disciplines will provide optimal care for cancer patients or cancer survivors and prevent secondary diseases of the heart. This is also the reason why centers are creating innovative units as an interface between different specialties to meet this increased need for interdisciplinarity. One example of this is the clinical unit of “Nuclear Cardiology” at the University Hospital Essen . Last buCardio-oncology represents an important new field that should be covered by multiple specialties as part of interdisciplinary teams. Nuclear medicine can provide important insights in the early detection of impending cardiotoxicity, assist in the monitoring of cardiotoxic therapy, and may also be used as a tracking tool in the investigation of cardiotoxicity of novel therapies. While nuclear cardiology has many promising techniques available, some of which are already being used in routine clinical practice, further studies are needed to investigate the full value of nuclear medicine techniques in the care of patients treated with cardiotoxic agents.This article summarizes the views of the EANM Cardiovascular Committee and the EANM Oncology & Theranostics Committee. It reflects recommendations for which the EANM cannot be held responsible. The recommendations should be taken into context of good practice of nuclear medicine and do not substitute for national and international legal or regulatory provisions.


Native T1 has become a pivotal parameter of tissue composition that is assessed by cardiac magnetic resonance (CMR). It characterizes diseased myocardium and can be used for prognosis estimation. Recent publications have shown that native T1 is influenced by short-term fluctuations of volume status due to hydration or hemodialysis.Patients from a prospective BioCVI all-comers clinical CMR registry were included, and native T1 and plasma volume status (PVS) were determined according to Hakim’s formula as surrogate markers of patient volume status. The primary endpoint was defined as combined endpoint of cardiovascular death or hospitalization for heart failure events, the secondary endpoint was defined as all-cause mortality.β = 0.11, p < 0.0001). Patients with volume expansion (PVS > −13%) showed significantly higher values for tissue markers than non-volume-overloaded patients . In Cox regression analysis both native T1 and PVS were independently predictive of the primary endpoint and all-cause mortality.A total of 2,047 patients were included since April 2017 . There was a significant although weak influence of PVS on native T1 (Despite a weak effect of PVS on native T1, its predictive power was not affected in a large, all-comers cohort. The native T1 relaxation time (in ms) differentiates between healthy and diseased myocardium in various clinical scenarios . Native Recent evidence shows that short-term fluctuations in a patient’s volume status impact T1 relaxation times. Luetkens et al. have shown that rapid dehydration and rehydration of healthy individuals significantly change native T1 times . The samThe plasma volume status (PVS), which is derived from anthropometric data and the hematocrit according to Hakim’s formula, is an easily accessible surrogate marker for the patient’s volume status and has been shown to provide prognostic information .It was the aim of the present study to test the hypothesis that the prognostic information obtained from native T1 times is independent of the hydration status as represented by PVS.2.2.1.The present study population was drawn from a prospective CMR/biobank (BioCVI) all-comers registry of patients who underwent CMR at a single center  between April 2017 and October 2022. Patients were enrolled in this study if they had a hematocrit measured immediately before the CMR examination.Clinical indications for CMR included the assessment of myocardial function, ischemia testing, viability testing, and differentiation of cardiomyopathy.2, and no late gadolinium enhancement (LGE) or perfusion defects were found. Patients were defined as ischemic cardiomyopathy if LVEF was ≤40% and there was ischemic LGE or at least two-vessel disease or ostial LAD disease according to the definition of Felker et al.  in the head-first supine position with an 18-array coil in agreement with the recommendations of the Society of Cardiovascular Magnetic Resonance (SCMR) . The sta2.3.Retrograde ECG-gated standard steady-state free precision (SSFP) CINE imaging was carried out using the following setting: TE 1.38 ms, TR 3.15 ms, flip angle 50°, bandwidth 962 Hz/px, field of view (FOV) 380 mm, voxel size 1.8 mm × 1.8 mm, slice thickness 8 mm, interslice gap 2 mm, and temporal resolution 30 ms. CINE sequences were generated in 11–15 short-axis views covering the whole ventricle from base to apex and in three long-axis views . To compensate for motion artifacts due to breathing or arrhythmias CINE images were acquired using compressed sensing.2.4.Modified look locker sequences ; TE 1.14 ms, TR 3.1 ms, bandwidth 108 Hz/px, FOV 350 mm, voxel size 1.4 mm × 1.4 mm × 8.0 mm, slice thickness 8 mm, adiabatic inversion pulse, 11 inversion times, and ECG-gated antegrade SSFP single-shot readout with 50° flip angle were acquired in three short-axis slices from base to apex following 5 into 3 planning.2.5.T2 maps were generated before the injection of contrast agent using ECG-gated antegrade T2 prep SSFP sequences generating with the breath-hold technique. Typical parameters were TE 1.34 ms, TR 4.2 ms, flip angle 12°, voxel size 1.8 mm × 1.8 mm, slice thickness 8 mm, and T2 prep with 0, 30, and 55 ms. Three short-axis slices were acquired in the same slice position as with T1 maps from base to apex.2.6.Inversion recovery-segmented gradient echo sequences were acquired 10–15 min after intravenous injection of gadolinium-dota  in short-axis and two-, three-, and four-chamber long-axis views. The delay between contrast bolus and acquisition was recorded by the technician. Typical parameters were TE 1.97 ms, TR 3.5 ms, flip angle 20°, bandwidth 289 Hz/px, FOV 370 mm, voxel size 1.3 mm × 1.3 mm × 8.0 mm, and slice thickness 8 mm.2.7.All analyses were performed on a commercially available workstation . For volumetric measurements, automatic contour detection by CVI42 was used excluding trabecularization. Contours were carefully checked by an experienced examiner (AR and JT with level 3 CMR certification from the German Society of Cardiology). End-systolic and end-diastolic volumes were indexed to body surface area . Ejection fraction (EF) and longitudinal (GLS), circumferential (GCS), and radial (GRS) strain were calculated as functional parameters.Global T1 was defined in the midventricular septum outside of LGE regions. A region of interest (ROI) of at least two voxels wide was drawn in an automatically generated parametric T1 map  by an experienced cardiologist (AR and JT), and mean T1 values were calculated. To avoid partial volume effects of the blood pool, the motion correction of the native magnitude pictures was carefully checked and ROI was placed in the center of the septum as recommended by the ConSept method .2.8.Plasma volume status was calculated according to the Hakim formula  as the da = 1,530 in males and 864 in females; b = 41 in males and 47.9 in females) and hospitalization for HF after 1 year.The secondary endpoint was all-cause mortality after 1 year.via telephone or in writing at least 1 year after the index CMR. All recorded endpoints were adjudicated in an endpoint conference.The clinical endpoints were recorded by standardized questionnaires administered either 2.10.p < 0.05 was considered as statistically significant. All tests were computed using Stata 17 .All metric parameters are presented as median and interquartile range. Categorial variables are presented as absolute frequencies and percentages. Normality of the data was checked by the Shapiro–Wilk test. The Wilcoxon rank-sum test was used to compare groups. Linear regression analysis was performed to examine the correlation between PVS, N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and T1 time. To account for possible heteroscedasticity, we performed robust regression analysis with the Huber-White variance estimator. Univariable Cox proportional hazard analysis was performed to evaluate the association between the study endpoints and CMR or clinical predictors. A multivariable model was fitted for the study endpoint to test the independent prognostic value of the predictors. As a rule of thumb one predictor per 10 events was included. A value of 3.Since April 2017, 2,941 patients were included in the registry. As hematocrit values from blood drawn immediately before the examination were only available for 2,183 patients, the remaining 758 patients were excluded. 136 patients were categorized as having active inflammation and were also excluded leaving 2,047 patients for the final analysis.Clinical and baseline CMR parameters are illustrated in 3.1.β = 0.11, p < 0.0001) and NT-pro-BNP .Dichotomizing our cohort at the reference cut-off of −13% yielded 1,110 non-volume-expanded and 937 volume-expanded patients. Native T1, T2, and NT-pro BNP were significantly higher in volume-expanded patients . Further clinical and CMR parameters in volume-overloaded and-contracted patients are shown in Dichotomizing our cohort at the prognostic cut off of −4% yielded 297 volume overloaded patients; here, the differences of native T1, T2 and NT-pro-BNP were as follows [1,138  vs. 1,124  ms; p = 0.12).Three-hundred and twelve patients had an eGFR less than 60 and were included in a subanalysis of patients with renal failure. Of these patients, 99 had elevated PVS above the prognostic cut off of −4%. Native T1 was higher in these patients compared to those with PVS less than −4% but the difference did not reach statistical significance  and NT-pro-BNP  cases after a mean of 430 days. T he primary endpoint of CV death and hospitalization for heart failure occurred in 46 patients (3%).The secondary endpoint of all-cause mortality was noted in 19 (0.6%) cases.In a univariable Cox regression model for the primary endpoint as well as the secondary endpoint both PVS and native T1 showed a significant effect on the endpoints.In a multivariable model for the primary endpoint cardiovascular death/heart failure hospitalizations, which also included EF, ECV, ESVi, GLS, and age, both native T1 time and PVS were independent predictors, with the interaction term being not significant .In a multivariable model with all-cause mortality as outcome variable and native T1 and PVS as independent variables, both were independently predictive of mortality, with the interaction term being not significant . Kaplan 4.There is a significant but only weak linear relation between PVS as a surrogate marker of volume status and native T1 time.Volume-expanded patients with a PVS > −13% have significantly elevated tissue markers compared to volume-contracted patients; however, this difference is small.Despite this marginal influence of volume status on the native T1 time, it remains independently predictive of MACE and all-cause mortality.Native T1 time is an essential parameter for the diagnosis of various cardiac diseases and can be used to estimate prognosis in ischemic as well as non-ischemic heart disease , 19. RecNative T1 maps are widely used and are a robust and reproducible method to estimate T1 relaxation time of the myocardium , 21. TheWhile the influence of free water on the native T1 is usually a short-term effect, it is fibrosis that has a long-lasting influence on T1 times and determines prognosis , 19. Witβ coefficient of 0.19 (p = 0.0001).Plasma volume status, determined according to Hakim’s formula, is a surrogate marker of volume status that can easily be derived from anthropometric data and hematocrit , 15. PVSApplying both cut-offs to our cohort we find indeed higher native T1 in volume-loaded patients. Patients above the reference value of −13% have 13 ms higher T1 times than patients below. This effect size is in good agreement with that of Luetkens et al., who found an 18 ms difference (at 1.5 T) in healthy volunteers after dehydration and rehydration . It is aEven in the absence of overt heart failure, MI, or non-ischemic cardiomyopathy, cardiovascular risk factors can enhance interstitial fibrosis and hence increase native T1 . This trHyperhydration is a distinctive feature of worsening chronic HF. The volume overload induces dyspnea and peripheral edema and leads to hospitalization more frequently than does low cardiac output , 30. ConHowever, the clinical implications of T1 are not critically affected by the volume T1 relationship. R2 in regression analysis was only 0.02, meaning that only 2% of the variance of native T1 values in our cohort can be attributed to volume fluctuations.Most importantly, the minimal effect of volume status on T1 times did not affect the prognostic implication of native T1. In univariate analysis both native T1 and PVS were predictive of both MACE and all-cause mortality. In multivariable analysis, T1 and PVS were independently predictive of MACE. Both parameters were independently predictive of death. The interaction term between native T1 and PVS was not significant with respect to both MACE and all-cause mortality.Myocardial fibrosis causes disintegration of the highly organized myocardial interstitium, resulting in impaired transduction of force and increased myocardial stiffness that together mediate systolic and diastolic dysfunction , 27, 32.Our study confirms the prognostic value of T1 in a large, all-comers cohort of patients with a comparatively high proportion of low-risk patients and normal findings on MR, which underlines the prognostic importance even outside specially selected cohorts of cardiomyopathy patients. Further, we demonstrated that the prognostic information conferred by T1 is not confounded by volume fluctuations.4.1.Our study has some limitations. The first limitation is the low number of endpoints reached during the observation period, which reduces the power of our findings. Only 19 patients died during follow up. This is due to the low-risk character of our cohort. Further, PVS is only a surrogate marker of volume expansion or contraction, although it has been well validated against direct volume quantification and its prognostic value has been shown . The adv4.2.Our data confirm the prognostic value of native T1 for MACE and mortality. Despite a weak effect of volume fluctuation on native T1, this does not hamper its prognostic impact.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by ethics committee of the Justus Liebig University, Gießen, Germany. The patients/participants provided their written informed consent to participate in this study.AR, JT, UF-R, and JW conceived and designed the study. CaH, JT, SK, and JW acquired clinical data. CaH, JT, JW, and AR acquired and analyzed imaging data. AR and UF-R executed the statistical analysis. JT drafted the manuscript. AR, EN, VP, CaH, UF-R, SK, ChH, and JT revised and amended critical parts of the manuscript. All authors contributed to the interpretation of the data and approved the final version of this manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The aim of the study was to verify the usefulness of the radiological cardiothoracic ratio as a potential marker of left ventricular hypertrophy assessed by echocardiography. The study included 96 patients (mean age: 49.52 ± 9.64 years). Chest radiograph in the PA projection and echocardiography were performed. In CR the measurement of the cardiothoracic ratio (CTR) was performed. Assuming CTR > 0.50, heart silhouette enlargement was diagnosed. In echocardiography, four types of left ventricular geometry were assessed: normal geometry (NG), concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH). It was shown that patients with an enlarged heart silhouette were characterized by a significantly more frequent occurrence of left ventricular hypertrophy (LVH) on echocardiography than patients with a nonenlarged heart silhouette. In the subgroup of patients with LVH compared to the subgroup of patients with normal left ventricular geometry, CTR values are statistically significantly higher, and heart silhouette enlargement is significantly more frequent. The criterion “CTR > 0.49” estimates LVH with a sensitivity of 93.3% and specificity of 82.7%, which translates into a high accuracy of 84.4%. By analyzing the prediction of left ventricular geometry types, high accuracy of CH prediction was obtained using the “CTR > 0.49” criterion of 80.2% (with a high sensitivity of 84.0% and a satisfactory specificity of 60.0%) and a high accuracy of EH prediction using the “CTR > 0.52” criterion of 71.9% (with high sensitivity 80.5% and low specificity 36.8%), as well as low CR prediction accuracy of only 57.3% . In summary, the radiological cardiothoracic ratio may be a moderate marker of left ventricular hypertrophy assessed according to standard echocardiographic criteria, provided that its cut-off point is standardized in each population of subjects. The cardiothoracic ratio (CTR) is defined as the ratio of the greatest transverse dimension of the heart (C weight) to the greatest dimension of the chest measured to the inner edge of the ribs (T weight) on the chest PA radiograph . Normal CTR is a widely used, time-saving, and non-cost-effective indicator when interpreting a chest X-ray to assess the size of the heart shape. In the literature, we find publications both about its important value and discrediting its importance in common use.A large, prospective cohort study on a group of almost 3.5 thousand 4-year follow-ups showed that in people undergoing hemodialysis, higher CTR is associated with a higher risk for both general and cardiovascular reasons . In the Despite the potential clinical applications of CTR described above, a common opinion is that CTR is of low clinical usefulness, which is also reflected in some studies that emphasize, for example, a weak correlation between CTR and the parameters of heart function –12. AnotWhen talking about the “large” left ventricular (LV), we should distinguish at least two terms describing it, namely, hypertrophy and dilatation. LV hypertrophy is an increase in the mass of the left ventricular secondary to an increase in the thickness of the left ventricular walls. The overgrown left ventricular, in addition to increasing the mass of the miokardium, may be of the correct size or enlarged , 16. LefThe main causes of left ventricular hypertrophy (LVH) are arterial hypertension, significant narrowing of the renal arteries, the so-called athlete's heart, aortic stenosis, aortic coarctation, hypertrophic cardiomyopathy, and aortic/mitral valve regurgitation. All the above-mentioned diseases, in connection with the increase in left ventricular volume load in certain stages, may lead to left ventricular dilatation , 18. EchThe aim of the study was to verify the usefulness of the radiological cardiothoracic ratio as a potential marker of left ventricular hypertrophy assessed by echocardiography.2. The general characteristics of the entire study group are presented in The study included 96 patients examined in the cardiology clinic recruited for the study based on the inclusion and exclusion criteria. The inclusion criteria for the study were as follows: age ≥ 18 years, clinical indications for echocardiography and chest radiograph in the PA projection, and informed written consent to participate in the study. The exclusion criteria from the study were a large volume of fluid in the pleural cavity/cavities, the presence of fluid in the pericardial sac, the coexistence of chronic respiratory diseases , past pneumonia in the past 6 months, cancer history, coexistence of diseases systemic diseases, history of congenital heart defects, previous thoracic, cardiosurgical and neurosurgical procedures in the thoracic spine, and changes in the therapy of chronic diseases in the past 6 months. The required sample size of 96 people was determined using a sample size calculator, adopting the following calculation criteria: population size 2 million, fraction size 0.5, maximum error 10%, and confidence level 95%. The mean age in the study group was 49.52 ± 9.64 years, height 1.67 ± 0.09 m, body mass 73.12 ± 9.88 kg, and BMI 26.30 ± 2.78 kg/mThe study was conducted as part of a research project entitled “Radiological cardiothoracic ratio as a predictor of heart size as assessed by echocardiography, computed tomography and magnetic resonance imaging.” The assumptions and protocol of the study were positively assessed by the local institutional bioethics committee (KB–414/2021).Basic anthropometric measurements were measured in all patients, and imaging examinations were performed: chest radiograph in the PA projection and echocardiography.The chest radiograph was performed using the standard method in the standing position in the posterior-anterior (PA) view. The radiograph was taken with a breath hold during the maximal inspiration phase, using a kilovolt of the 120 kV X-ray tube. All radiographs met the radiological criteria for the correct acquisition of the X-ray image.For the purposes of the current study of retrospective CTR measurements in all chest radiographs performed, one specialist in radiology and imaging diagnostics, holding institutional individual certification in the field of cardiovascular radiology, performed it. The measurement of the cardiothoracic ratio (CTR) was performed using a diagnostic radiological station that met the applicable legal requirements for the assessment of X-rays. The maximum width of the heart's silhouette (C width) and the maximum width of the chest (T width) were measured. The CTR value was obtained by dividing the measured C width value by the T width value. Assuming CTR > 0.50, enlargement of the heart silhouette was diagnosed. The method of measuring CTR on a chest radiograph in the PA projection is presented in 3 -LVEDd3] + 0.6; LVMI = LVM/BSA ; RWT = (IVSDd + PWDd)/LVEDd.Transthoracic echocardiography was performed using a standard examination protocol using the ALOKA ProSound 6 . Using the M-mode presentation under the control of a two-dimensional examination , the dimensions of the lumen and the thickness of the walls of the left ventricular were measured: left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVESd), interventricular septum diastolic diameter (IVSDd), and posterior wall diastolic diameter (PWDd). Left ventricular dimensions and left ventricular wall thickness were used to estimate left ventricular mass (LVM), left ventricular mass index (LVMI), and relative wall thickness (RWT). The following mathematical formulas were used in the estimation: LVM = 0.8 × [1.04 × (LVEDd + PWDd + IVSDd)2 in men or ≤ 110 g/m2 in women; CR when RWT > 0.45 and LVMI ≤ 125 g/m2 in men or ≤ 110 g/m2 in women; CH when RWT > 0.45 and LVMI > 125 g/m2 in men or > 110 g/m2 in women; EH when RWT ≤ 0.45; LVMI > 125 g/m2 in men or > 110 g/m2 in women. Moreover, patients diagnosed with CR, CH, and EH were classified into the general group of patients with left ventricular hypertrophy (LVH). For the purposes of the present study, all echocardiographic examinations were performed by one specialist in cardiology with 20 years of experience.The estimated LVMI and RWT values were used as criteria for classifying four types of left ventricular geometry: normal geometry (NG), concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH). NG was diagnosed when RWT ≤ 0.45 and LVMI ≤ 125 g/mEchocardiographic examination and chest radiograph were performed in the shortest possible time interval, not longer than 7 days. The mean time interval between the performed imaging examinations was 4.32 ± 1.03 days.t-test. The null hypotheses for nonnormally distributed variables were tested with the Mann–Whitney U test. For qualitative variables, percentages were calculated. The null hypotheses for qualitative variables were tested with the chi-square test. To determine the potential linear relationships between the analyzed quantitative variables, a correlation analysis was performed. Pearson's correlation coefficients were established for quantitative variables with a normally distributed, and Spearman's correlation coefficients for quantitative variables with a distribution other than normal. Moreover, an analysis of the prediction accuracy assessment was performed, in which the proposed cut-off points for the predictors were estimated based on ROC (Receiver Operating Characteristic) curves. The level of statistical significance was p < 0.05.Statistical analysis was performed using the Dell Statistica 13 statistical package . For quantitative variables, arithmetic means and standard deviations were calculated. The W Shapiro–Wilk test was used to check the normality of the distribution of variables. The null hypotheses for normally distributed quantitative independent variables were tested with the 2, while the RWT was -0.48 ± 0.07. Left ventricular hypertrophy (LVH) was found in 84.4% of patients, CR in 49.0% of patients, CH in 15.6%, and EH in 19.8% of patients. The study group was characterized by a CTR of 0.51 ± 0.04. Enlarged heart silhouette was diagnosed in 30.2% of patients. Selected variables from imaging studies are summarized in LVMI in the studied group of patients was 107.80 ± 31.05 g/mComparing the subgroups of patients distinguished based on the CTR criterion, it was shown that patients with an enlarged heart silhouette on the chest radiograph in the PA projection were characterized by a significantly more frequent occurrence of left ventricular hypertrophy (LVH) on echocardiography than patients with a nonenlarged heart silhouette. There is a significant difference between patients with an enlarged heart silhouette and patients with a nonenlarged heart silhouette of the more frequent incidence of left ventricular concentric hypertrophy in the first of these subgroups. The left ventricular geometry in the subgroups distinguished based on the heart silhouette enlargement criterion is presented in In a comparative analysis of the subgroups distinguished based on the presence of LVH, it was found that in the subgroup of patients with LVH compared to the subgroup of patients with normal left ventricular geometry, CTR values are statistically significantly higher, and heart silhouette enlargement is significantly more frequent.When comparing the subgroups of patients with different types of left ventricular geometry in echocardiography, statistically significant higher CTR values were observed in the CR, CH, and EH subgroups than in the NG subgroup and also in the CH and EH subgroups than in the CR subgroup. Moreover, heart silhouette enlargement was significantly more frequent in the subgroup of patients with CR, CH, and EH than in the subgroup of patients with NG and also in the subgroup of patients with CH than in the subgroup of patients with CR. The values of the cardiothoracic ratio in the subgroups distinguished based on the geometry of the left ventricular are presented in r = 0.38, p < 0.05), LVM and CTR , and LVMI and CTR , The correlation analysis showed the existence of statistically significant positive linear relationships between LVEDd and CTR  and the CTR criteria determined based on the performed ROC curves presented in Figures The CTR criteria established based on the ROC curves made were each time characterized by higher predictive accuracy than the standard CTR criterion defining the heart silhouette enlargement. In the studied group of patients, the criterion “CTR > 0.49” estimates LVH with a sensitivity of 93.3% and specificity of 82.7%, which translates into a high accuracy of 84.4%. By analyzing the prediction of left ventricular geometry types, high accuracy of CH prediction was obtained using the “CTR > 0.49” criterion of 80.2% (with a high sensitivity of 84.0% and a satisfactory specificity of 60.0%) and a high accuracy of EH prediction using the “CTR > 0.52” criterion of 71.9% (with high sensitivity 80.5% and low specificity 36.8%), as well as low CR prediction accuracy of only 57.3% .p < 0.05) between LV hypertrophy and CTR while indicating a weak correlation between CTR and LV enlargement [The results of our research have shown that CTR may be a helpful indicator in the prediction of LVH, especially in the subgroup of patients with concentric hypertrophy. High sensitivity, specificity, and accuracy should be emphasized while maintaining the CTR > 0.49 condition. Based on the compiled data, it can be concluded that each time CTR > 0.49 should be associated with the consequence of further investment regarding, in particular, the thickness of the LV walls. However, there are few studies in the literature comparing echocardiographic and CTR values in the assessment of LV size and its wall thickness. In 2006, a publication was published that investigated the correlation of a chest radiograph and a transthoracic ultrasound of the heart in the assessment of cardiomegaly in patients with arterial hypertension. Researchers have demonstrated, like us, that there is a significant correlation  assess whether this situation also applies to the wider population . In the Comparing our research group with the group studied by Costa et al. , in compA study that assessed the clinical manifestations and course of HCM in the pediatric population showed an increased CTR , and echocardiography confirmed different LVH morphologies in all patients , which mResearchers from Korea tried to create a system based on several criteria (including electrocardiography and CTR) that would allow effective prediction of LVH among asymptomatic hypertensive patients. The researchers emphasized the high negative predictive value of CTR in detecting LVH, and the CTR introduced into their method as an additional risk factor significantly improved the accuracy of the LVH suspicion . SimilarThis is another finding of our research on the predictive suitability of CTR. We previously demonstrated that in patients with suspected pulmonary embolism during COVID-19, CRT can be considered as a prognostic factor for right ventricular enlargement, especially as a negative predictor of right ventricular enlargement in the case of lower CTR values .Summing up, it should be emphasized that despite the common belief that the CTR measurement value is low as a marker of LV hypertrophy, our research seems to fit in with the evidence provided by researchers in recent years regarding the predictive utility of the above radiological parameter. The strength of our study is also demonstrated that among the echocardiographically assessed types of left ventricular geometry, the radiological cardiothoracic ratio can be considered with high predictive accuracy as a marker of concentric hypertrophy and also as a marker of eccentric left ventricular hypertrophy. However, great caution should be exercised when trying to predict concentric remodeling of the left ventricular based on the radiological cardiothoracic ratio.Radiological cardiothoracic ratio may be a moderate marker of left ventricular hypertrophy assessed according to standard echocardiographic criteria, provided that its cut-off point is standardized in each population of subjects.Among the echocardiographically assessed types of left ventricular geometry, the radiological cardiothoracic ratio can be considered with high predictive accuracy as a marker of concentric hypertrophy and also as a marker of eccentric hypertrophy. Caution should be exercised in predicting concentric remodeling based on the radiographic cardiothoracic ratio.


To explore the clinical application of echocardiography in assessing left ventricular diastolic function in patients with acute pulmonary embolism (APE).  About 90 patients with APE treated in our hospital from March 2016 to March 2019 were enrolled as the study group. The enrolled patients were assigned into three groups in accordance with the risk stratification of APE, with 30 patients in each group, including high-risk group, medium-risk group, and low-risk group. Approximately 90 healthy persons who underwent physical examination in the same period were enrolled as the control group. The two groups were used to analyze the clinical value of echocardiography in evaluating left ventricular diastolic function in patients with APE and to explore the correlation between left ventricular diastolic function and different risk stratification of APE. P < 0.05). Secondly, we compared the echocardiographic side values of patients with different APE risk stratifications: (1) RVED/LVED, PASP: low‐risk group < medium‐risk group < high‐risk group; (2) LVEDV, LVESV, LVSV, LVEF: low‐risk group > medium‐risk group > high‐risk group (P < 0.05). The routine echocardiographic findings of APE patients: M-type left ventricular wave group of pulmonary embolism (PE) indicated right ventricular enlargement and interventricular septum shifted to the left ventricle; short-axis section of PE artery indicated thrombosis at the opening of the right pulmonary artery (indicated by arrow); long-axis section of the left ventricle of PE indicated right ventricular enlargement ; four-chamber view of PE indicated enlargement of the right atrium and the right ventricle, and interventricular septum shifted like left ventricle. In terms of mitral annulus displacement, early diastolic ESD and ELD in the study group were lower compared to those in the normal control group, while late diastolic ASD and ALD in the study group were higher compared to those in the normal control group (P < 0.05). The results of Pearson correlation analysis indicated that there was a positive correlation between RVED/LVED, PASP, and APE risk stratification, while APE risk stratification was negatively correlated with LVEDV, LVESV, LVSV, and LVEF (P < 0.05).  First of all, we compared the side values of echocardiography. Compared to the control group, right ventricular end-diastolic diameter/left ventricular end-diastolic diameter (RVED/LVED) and pulmonary artery systolic pressure (PASP) in the study group were higher, while left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular volume per stroke (LVSV), and left ventricular ejection fraction (LVEF) in the study group were lower ( Echocardiography attaches importance to the evaluation of left ventricular diastolic function in APE. The side value of echocardiography can sensitively reflect the changes of left ventricular diastolic function in APE. The predictive value in the diagnosis of APE is better than other traditional parameters of left ventricular diastolic function, especially in patients with different APE risk stratifications. There is a remarkable correlation between the changes of left ventricular diastolic function and different APE risk stratifications. Echocardiographic measurement can be employed to assess left ventricular diastolic function in APE, which can be developed in clinical treatment and prognosis evaluation to provide a new evaluation method. Acute pulmonary embolism (APE) is a series of pathophysiological syndromes caused by endogenous or exogenous emboli blocking the pulmonary circulatory system, containing fat embolism syndrome, pulmonary thromboembolism, air embolism, amniotic fluid embolism, and tumor embolism . PulmonaWith more attention to left ventricular diastolic function, more clinical evidence indicates that the change of left ventricular diastolic function is a crucial factor in the morbidity and mortality of cardiovascular diseases, such as heart failure, pulmonary hypertension, PE, cardiomyopathy, and congenital heart disease. Therefore, the evaluation of left ventricular diastolic function is very crucial for the clinical management and prognosis of cardiovascular disease . The AmeAbout 90 patients with APE treated in our hospital were enrolled as the study group from March 2016 to March 2019. The enrolled patients were assigned into three groups according to the APE risk stratification, with 30 patients in each group, containing high-risk group, medium-risk group, and low-risk group. A total of 90 healthy persons who underwent physical examination in the same period were enrolled as the control group. In the control group, the age was 43-74 years old, with an average age 65.91 ± 3.63, containing 36 males and 54 females, while in the study group, the age was 44-76 years old, with an average age 65.96 ± 3.58, containing 35 males and 55 females. There exhibited no statistical significance in the general data. This study was permitted by the Medical Ethics Association of our hospital, and all patients provided informed consent.APE risk stratification criteria are  as folloDiagnostic criteria: to observe whether the echocardiographic signs of thrombus in the right atrium, right ventricle, pulmonary artery trunk, and bifurcation can be observed by echocardiography, whether the indirect signs of increased pulmonary artery pressure, decreased activity of right ventricular wall, and increased right cardiac load could be observed.Inclusion criteria: (1) APE was confirmed by pulmonary angiography or pulmonary CTA; (2) blood gas analysis indicated hypoxemia; plasma D-dimer was positive; APE was diagnosed according to its symptoms, signs, ultrasound, and laboratory examination.Exclusion criteria: patients with poor ultrasound window, thrombolysis taboo, and other heart and lung diseases.All patients were examined by echocardiography: emergency echocardiographic examination was performed in all patients with echocardiographic diagnostic equipment . The examination included parasternal artery short-axis section, parasternal left ventricular long-axis section, parasternal four-chamber view, and apical four-chamber view. The transverse and anterior-posterior diameters of left ventricle and right ventricle at the end of diastole were measured. The transverse diameter of the right atrium, the transverse diameter of the left atrium and the anterior and posterior diameter of the left atrium at the end of systole, the width of the main pulmonary artery at the end of systole, the amplitude of motion of the anterior wall of the right ventricle, the posterior wall of the left ventricle, and the interventricular septum were compared, whether there are thrombus echo signs in the right atrium, right ventricle, pulmonary artery trunk, and bifurcation.Left ventricular end-diastolic diameter (LVED), right ventricular end-diastolic diameter (RVED), and pulmonary artery systolic pressure (PASP) were calculated and evaluated by measuring right atrial pressure and maximum tricuspid regurgitation pressure difference. Patients were instructed to hold their breath, and S5-1 probe was used to measure left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular volume per stroke (LVSV), and left ventricular ejection fraction (LVEF) at apical four-chamber and two-chamber views by Simpson's biplane method.The early diastolic posterior septal displacement (ESD) and the left ventricular lateral wall displacement (ELD) of early diastolic mitral annulus were measured automatically by taking two points at the beginning and end of early diastole on the motion curves of the two sites. Similarly, the late diastolic mitral annulus posterior septal displacement (ASD) and late diastolic left ventricular lateral wall displacement (ALD) were automatically measured on the motion curve at two points at the beginning and end of late diastole.n(%)]. The chi-square partition method was employed for the pairwise comparison, and the measurement data of normal distribution was presented by .The data of this study were analyzed by SPSS 26.0; the counting data were presented by [P < 0.05). All the data results are indicated in First of all, we compared the side values of echocardiography. RVED/LVED and PASP in the study group were higher compared to those in the control group, while LVEDV, LVESV, LVSV, and LVEF in the study group were lower compared to those in the control group (P < 0.05). All the data results are indicated in Secondly, we compared the echocardiographic side values of patients with different APE risk stratifications: RVED/LVED, PASP: low‐risk group < medium‐risk group < high‐risk group; LVEDV, LVESV, LVSV, LVEF: low‐risk group > medium‐risk group > high‐risk group ; long-axis section of the left ventricle of PE indicated right ventricular enlargement ; four-chamber central section of PE indicated enlargement of right atrium and right ventricle, and interventricular septum shifted like left ventricle Figures .P < 0.05). See Next, we compared the mitral annulus displacement. Compared to the normal control group, the early diastolic ESD and ELD in the study group were lower, while the late diastolic ASD and ALD in the study group were higher (P < 0.05). All the data results are indicated in Finally, we analyzed the correlation between different APE risk stratifications and left ventricular diastolic function. The results of Pearson's correlation analysis indicated that RVED/LVED, PASP, and APE risk stratification were positively correlated, while LVEDV, LVESV, LVSV, and LVEF APE risk stratification were negatively correlated (PE is a pathophysiological syndrome characterized by endogenous or exogenous emboli blocking pulmonary vessels, causing pulmonary circulation disturbance, progressive right heart failure, dyspnea, chest pain, hypotension, and other clinical manifestations . APE leaAPE is not a common cardiopulmonary disease; the condition is complex and lacks specific symptoms, so it is easy to miss diagnosis, have misdiagnosis, and have high mortality . APE oftTherefore, accurate evaluation of cardiac function in patients with APE is particularly important to judge the condition and prognosis . APE canThe clinical symptoms of APE are diverse and lack specificity, ranging from occult, hemoptysis, chest pain, dyspnea, to hemodynamic instability and even syncope at first onset in some patients . The cliImaging examination is an important way to evaluate the changes of left ventricular function . CompareThe results of this study indicated that compared with the control group, RVED/LVED and PASP in the study group increased remarkably, while LVEF, LVEDV, and LVESV decreased significantly, suggesting that there was damage to left ventricular function in patients with APE . The twoIn summary, echocardiography is of great significance in the evaluation of left ventricular diastolic function in APE. The side value of echocardiography can sensitively reflect the changes of left ventricular diastolic function in APE, and its predictive value in the diagnosis of APE is better than other traditional parameters of left ventricular diastolic function, especially in patients with different APE risk stratifications. There is a remarkable correlation between the changes of left ventricular diastolic function and different APE risk stratifications. Echocardiographic measurement is simple and can be employed to evaluate left ventricular diastolic function in APE, which can be developed in clinical treatment and prognosis evaluation to provide a new evaluation approach.


Patients with a Fontan circulation lack a sub-pulmonary ventricle with pulmonary blood flow passively redirected to the lungs. In the Fontan circulation, ventilation has a significant influence on pulmonary blood flow and cardiac output both at rest and with exercise. Children and adults with a Fontan circulation have abnormalities in lung function. In particular, restrictive ventilatory patterns, as measured by spirometry, and impaired gas transfer, as measured by the diffusing capacity of carbon monoxide, have been frequently observed. These abnormalities in lung function are associated with reduced exercise capacity and quality of life. Moderate to severe impairment in lung volumes is independently associated with reduced survival in adults with congenital heart disease. Skeletal and inspiratory muscle weakness has also been reported in patients with a Fontan circulation, with the prospect of improving respiratory muscle function through exercise training programs. In this review, we will present data on cardiopulmonary interactions in the Fontan circulation, the prevalence and severity of impaired lung function, and respiratory muscle function in this population. We will discuss potential causes for and consequence of respiratory impairments, and their impact on exercise capacity and longer-term Fontan outcome. We aim to shed light on possible strategies to reduce morbidity by improving respiratory function in this growing population of patients. Children born with univentricular anatomy undergo procedures in early life resulting in the Fontan circulation. This is routinely performed as staged procedures, resulting in systemic venous return from the superior and inferior vena cava (SVC and IVC) draining passively into the pulmonary arteries, bypassing a sub-pulmonary pump. The completion of the Fontan circuit reduces desaturation and unloads the functionally single ventricle. Heart rate, ventricular function, respiration, and skeletal and respiratory muscle strength all affect the performance of the Fontan circulation.Since its initial description, the Fontan procedure has undergone several modifications to improve the circulation's efficiency and reduce overall morbidity and mortality. However, morbidity in this population is still high. The Fontan circulation results in high systemic venous pressure, chronic venous congestion, and reduced pulmonary blood flow, cardiac output, and ventricular function. In addition, multiple other adverse factors may be present including chronotropic incompetence, non-uniform distribution of pulmonary blood flow, chest wall and spinal deformities, pleural adhesions, diaphragmatic palsy, and respiratory and skeletal muscle weakness. With advances in surgical techniques and medical therapy, there are an increasing number of Fontan patients surviving to older adulthood. However, complications related to the Fontan circulation are common, including ventricular systolic and diastolic dysfunction, arrhythmia, venous thrombosis, protein-losing enteropathy, plastic bronchitis, ascites, and hepatic fibrosis and carcinoma , 2. ApprAbnormal lung function and respiratory muscle weakness have been documented in Fontan patients. Moderate to severe impairment in lung volumes are independently associated with reduced survival in adults with congenital heart disease . Fontan Respiration induces changes in intrathoracic pressures and thereby lung volumes, which in turn affects preload, afterload, and stroke volume. Lauson et al. described the influence of respiration on changes in circulatory pressure in normal subjects, those with chronic lung disease, and those with rheumatic heart disease . They foSystemic venous return from the SVC and IVC are dependent on the existence of a pressure gradient between the extra-thoracic venous system and the right atrium . The venRiggs and Snider also noted an increase in RV filling during inspiration, in both early and late diastole . Comparein vitro, demonstrated that a contractile chamber did not improve forward flow and did in fact limit pulmonary forward flow detrimental to the circulation by increasing upstream resistance . The initial belief was that a contractile chamber (right atrium) acting as a pump to drive pulmonary forward flow was important in the Fontan circulation . Subsequsistance .The importance of spontaneous respiration in the Fontan circulation was highlighted by Fontan and Baudet in 1971, stating that “respiratory assistance should be stopped early because positive pressure prevents central venous return” . SubsequRedington et al. also demonstrated augmentation of pulmonary blood flow during inspiration, and attenuation or cessation of this antegrade flow at beginning of expiration in the Fontan circulation . They foConsistent with previous studies demonstrating an increase in venous return to the RV, Hsia et al. confirmed higher forward flow in the hepatic veins and IVC during inspiration in both normal and Fontan subjects . In normIn summary, these studies demonstrate the alterations from normal in cardiopulmonary interactions in the Fontan circulation . The effUsing phase-contrast techniques, cardiac magnetic resonance imaging (CMR) provides a unique opportunity to study cardiopulmonary interactions of the Fontan circulation. Respiratory variability in flows through the Fontan circulation has been shown with CMR, with increased flow rates during inspiration –29. For Using real-time free breathing methods, Wei et al. measured respiration and flow in Fontan subjects during rest and exercise . They alSignificant increases in systemic venous and aortic flow pulsatility with respiration have been shown, with variability between vessels , 30. GabIn a small cohort, where we were examining the hemodynamic responses to inspiratory muscle training (IMT), we used CMR to assess aortic and pulmonary flow at rest and during exercise . We founCMR has further evaluated changes in pulmonary blood flow during exercise in the Fontan circulation. Changes in pulmonary forward flow are both cardiac and respiratory dependent. Systemic venous return, particularly IVC return, and pulmonary antegrade flow increases during inspiration at rest.In the normal circulation, cardiac output is a function of stroke volume  and heart rate. Several factors can potentially limit cardiac output in the Fontan circulation. Primarily, the lack of a sub-pulmonary ventricle results in preload insufficiency , 33 withNumerous studies have shown the importance of PVR in the Fontan circulation and is now thought to be the major determinant of cardiac output , 43. As Pulmonary vasculature development is abnormal in patients with complex congenital heart. Antenatal hemodynamic factors can alter pulmonary artery size and arborization, and pulmonary venous and lymphatic anatomy. The connection between the cardiac and pulmonary circulations is evident embryologically with lung endoderm protruding into the mesoderm as the heart tube elongates and folds . By 20 wAugmentation of cardiac output is usually achieved by increases in heart rate, preload and/or myocardial contractility, and reduced afterload. With exercise, for example, biventricular stroke volume increases in the setting of adequate preload reserve . In the Pulmonary blood flow and PVR are the major determinants of cardiac output in the Fontan circuit and are significantly affected by respiration. In a normal circulation, PVR is the main determinant of pulmonary afterload and is affected by lung volumes . ReductiPositive pressure ventilation (PPV) is frequently used in the management of respiratory failure in postoperative cardiac patients. However, it has been shown to reduce cardiac output likely secondary to increases in PVR and reduced systemic venous return. The hemodynamics of a Fontan circulation are dependent on low PVR and sufficient venous return, and hence the adverse effect of PPV is augmented in the Fontan circulation . PPV canSince the nineteenth century, negative pressure ventilation (NPV) has been used in paralyzed patients with respiratory insufficiency. It has been shown to improve both pulmonary blood flow and cardiac output, particularly in the Fontan circulation, and is associated with improved systemic venous return , 60–63. Shekerdemian et al. converted patients in intensive care after Fontan completion from PPV to NPV and demonstrated acute improvement in pulmonary antegrade flow . This waLung volume, alveolar surface area, and number increases from 29 weeks' gestation to at least 12 weeks postnatally, with a close association to body weight . During Prior to Fontan completion, neonatal palliation of pulmonary blood flow may result in abnormalities of pulmonary vascular development. After Fontan completion, pulmonary blood flow is non-pulsatile with altered wall shear stress and reduced pulmonary endothelial function . The deg1), forced vital capacity (FVC), and a normal or high FEV1/FVC ratio  of subjects with low FVC . This lo pattern . Moderat pattern . Restric pattern .1 % predicted and self-reported quality of life scores, related to physical functioining  and demonstrated that during follow-up (0.7–17.5 years), vital capacity decreased significantly . The sigtioining .2) and reduced exercise capacity, and is a predictor of survival in adults with congenital heart disease , with a restrictive ventilatory pattern (2) slope, a marker of ventilatory efficiency, during exercise was significantly elevated. Their findings suggest that the restrictive pattern of lung function in Fontan subjects contributes to an abnormal ventilatory response to exercise. Previous studies have also shown elevated ventilatory equivalence of oxygen (VE/VO2) at both rest and exercise in functionally single ventricle patients   .2, and a stronger determinant than ventricular morphology or dysfunction (2 slope were more likely to have a low breathing reserve (BR), suggestive of ventilatory limitation of exercise. In comparing those with ventilatory limitation of exercise (defined as BR <20%) and those with presumed cardiac limitation (BR > 20%), low FVC, high VE/VCO2 slope, and high body mass index independently predicted ventilatory limitation.Impairments in pulmonary function can impact exercise capacity, with Opotowsky et al. demonstrating that a low FVC was predictive of low peak VOfunction . They al2  are required to determine the exact etiology of low DLCO in the Fontan population.2O (77±27%) compared with 102 ± 32 cmH2O in the control group. Inspiratory muscle weakness was greater than expiratory muscle weakness. MIP and maximal expiratory pressure (MEP) correlated significantly with peak VO2. In addition, subjects with globally reduced respiratory muscle strength (both MIP and MEP) had lower maximal voluntary minute ventilation, which at peak exercise was also associated with peak VO2. Similarly, Turquetto et al. examined respiratory muscle strength in 27 Fontan patients (2O (63 ± 16% predicted) in males and 81 ± 33 cmH2O (71 ± 32% predicted) in females. SNIP was measured at 99 ± 24 cmH2O (72 ± 31%) in males and 84 ± 13 cmH2O (82 ± 12%) in females. Furthermore, they found an association between SNIP and peak VO2. This respiratory muscle weakness may contribute to reduced lung volumes, as seen in Fontan patients.Greutmann et al. have documented generalized muscle weakness involving the skeletal and respiratory muscles in patients with congenital heart disease . They stpatients  by usingWith the identification of pulmonary abnormalities in Fontan patients, research studies are now determining ways to improve lung function, with the hope to improve exercise capacity, quality of life, and morbidity. With the identification of reduced skeletal and respiratory muscle strength, and better understanding of altered cardiopulmonary interactions in the Fontan circulation, mechanisms to improve lung function have been proposed.Like skeletal muscles, respiratory muscles can be trained with regular pressure loading. Respiratory muscle weakness affects exercise capacity by predisposing them to fatigue and an increased perception of dyspnea . During IMT has been studied in a number of conditions including chronic heart failure –91. It h2), and resting cardiac output in young Fontan patients , ventilatory efficiency of exercise  in Fontan patients, training both the inspiratory and expiratory muscles . They usThese studies are suggestive that with the correct training regime, including adjustments of the load according to the patient's individual MIP, both IMT and respiratory training have the potential to improve exercise capacity. However, larger studies need to be undertaken to determine the potential benefits, particularly in the setting of other physical activity programs. IMT is a simple and safe intervention that can be used to improve respiratory muscle strength.Due to the effects of gravity, when exercising, peripheral skeletal muscles need to pump against gravity to maintain diastolic filling. In the Fontan circulation, pulmonary blood flow is dependent on IVC return. Lower limb venous compliance correlated with calf surface area and muscle mass . CordinaHedlund et al. examined the effects of endurance training on Fontan patients, through individualized endurance training programs, including supervised weekly training sessions for 45 min over the duration of 12 weeks . These pPatients with a Fontan circulation have abnormal cardiopulmonary interaction, in the setting of their systemic and pulmonary circulations being in series. Due to this, the physiological changes with inspiration are more pronounced in subjects with a Fontan circulation, and respiration has a more crucial role in regulating cardiac output. The critical dependence of ventilation in determining cardiac output in the Fontan circulation is highlighted by the acute use of NPV or BPV immediately post-Fontan completion to improve antegrade pulmonary blood flow and cardiac output. Fontan patients have been shown to have reduced lung volumes with restrictive lung disease, and abnormal lung gas transfer. The exact etiology of these changes still needs to be studied in more detail. In addition, Fontan patients have reduced skeletal and respiratory muscle strength, further limiting exercise capacity. We and others have shown potential benefits to respiratory muscle training. The benefits of aerobic and skeletal muscle training with or without respiratory muscle training remain to be determined.KL and JA wrote and revised the article. Both authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Congenital heart malformations are cardiac and/or vascular structural abnormalities that appear before birth, the majority of which can be detected prenatally. The latest data from the literature were reviewed, with reference to the degree of prenatal diagnosis regarding congenital heart malformations, as well as its impact on the preoperative evolution and implicitly on mortality. Studies with a significant number of enrolled patients were included in the research. Prenatal congenital heart malformations detection rates were different, depending on the period in which the study took place, the level of the medical center, as well as on the size of enrolled groups. Prenatal diagnosis in critical malformations such as hypoplastic left heart syndrome, transposition of great arteries and totally aberrant pulmonary venous drainage has proven its usefulness, allowing an early surgical intervention, thus ensuring improved neurological development, increasing the survival rate and decreasing the rate of subsequent complications. Sharing the experience and results obtained by each individual therapeutic center will definitely lead to drawing clear conclusions regarding the clinical contribution of congenital heart malformations prenatal detection. Congenital heart malformations are cardiac and/or vascular structural abnormalities that appear before birth, the majority of which can be detected prenatally. Having an incidence between 0.8 and 1.2%, congenital heart disease (CHD) is the most frequent malformative pathology diagnosed at birth and the major cause of death in the first year of life [Although it is the most diagnosed malformative pathology, the etiology of CHD is less understood . In mostFrom the etiological point of view, certain environmental causes were identified that led to the increase in the incidence of heart malformations. Thus, after the Chernobyl incident in 1986, there was an increase in CHD cases. The same tendency was observed after the Fukushima nuclear accident .Along with prematurity specific pathology, congenital heart malformations are the most frequent causes of hospitalization in neonatal intensive care units. The clinical differentiation between cardiogenic and septic shock is difficult in newborns. Therefore in the event of clinical signs of shock the presence of a severe cardiac structural defect must be excluded using imaging techniques such as ecochardiography. The sepsis rate in these patients may increase when a critical heart malformation is confirmed becouse of the necessary therapeutic procedures , central vascular approach, immunosuppression, prematurity, and possibly associated extracardiac malformative pathology.Newborns diagnosed with critical heart malformation need prolonged supervision in the intensive care unit, both in the preoperative period, but especially in the postoperative period. There is a clear correlation between the length of hospitalization in the intensive care unit and the mortality rate in the first year of life. The main cause of heart failure in newborns is the presence of a critical congenital malformation at this level. Newborns with congenital heart malformation who develop severe heart failure, pulmonary edema, severe arrhythmias or any other condition that endangers the cardiac status require intensive care therapeutic measures. In case of a critical heart malformation prenatal diagnosis it is recommended for the birth to take place in a level 3 medical center with a Neonatal Intensive Care Service. The therapeutic measures in the intensive care service are aimed at ensuring adequate tissue perfusion and obtaining optimal oxygenation.The aim of this article was to corroborate the latest data from the literature regarding the influence of prenatal diagnosis on mortality and preoperative complications of the newborn with congenital heart disease. The latest data from the literature were reviewed, with reference to the degree of prenatal diagnosis regarding congenital heart malformations, as well as its impact on the preoperative evolution and implicitly on mortality. Studies with a significant number of enrolled patients were included in the research.Prenatal CHD detection rates were different, depending on the period in which the study took place, the level of the medical center, as well as on the size of enrolled groups. Prenatal diagnosis of heart malformations may increase the survival rate and decrease the rate of subsequent complications. Ensuring the birth takes place in a medical center with neonatal intensive care unit, cardiac surgery and interventional cardiology services becomes crucial in the management of cardiac malformations. Thus, the risk of hemodynamic instability in the early neonatal period is significantly reduced . Table .Prenatal diagnosis of congenital heart malformations has become a routine examination among high-risk mothers, the detection rate being variable depending on the evaluation center ,13. The According to Sun et al. fetal echocardiography is recommended to be performed in the following maternal conditions: gestational diabetes or pregestational diabetes, lupus or Sjogren’s syndrome with positive serology (anti-SSA/anti-SSB antibodies), obtaining pregnancy through assisted reproduction techniques, viral infection with the rubeola virus, Coxsackie or Parvovirus, uncontrolled phenylketonuria, as well as in the case of a first-degree relative with congenital heart disease. There are also a series of fetal conditions that require a fetal echocardiography. Raising the suspicion of a structural heart defect during routine obstetric ultrasound, detecting a fetal arrhythmia, identifying an extracardiac malformation or a chromosomal defect require additional investigations. Nuchal translucency over 3 mm, fetal hydrops, monochorionic twin pregnancies or placental malformations are situations in which a fetal echocardiography must be performed ,8.The prenatal detection of a congenital heart malformation must be followed by the identification of other possible associated anomalies, and thus providing more time to set treatment strategies and to better understand the prognosis of these still unborn babies, but at the moment the detection rate is variable ,11,15. UThe rate of prenatal detection of congenital heart malformations has improved significantly in recent decades. Van Velzen et al. conducted a cohort study over a period of ten years, carried out in three third-level centers, including over 700 newborns. They tracked the degree of accuracy between prenatal and postnatal diagnosis. Over 80% of the subjects had an anatomically correct diagnosis .There are studies in which it was not possible to demonstrate the decrease in mortality among newborns with a prenatal diagnosis of congenital heart malformation ,15. ThisChakraborty et al. demonstrated the fact that the lack of prenatal diagnosis is more frequently associated with acidosis, considering the late initiation of Prostaglandin E1 therapy in ductal-dependent cardiac malformations. The lack of prenatal diagnosis and the onset of sepsis-like clinical signs lead to the more frequent use of antibiotics among these patients. An increase in the survival rate in ductal-dependent cardiac malformations with prenatal diagnosis was also observed .The retrospective research carried out by Gupta et al. over a period of 5 years included approximately 300 newborns, with a chronological age of less than 10 days and a gestational age of more than 34 weeks. The prenatal detection rate of congenital heart malformation was 62%. This was not influenced by sex, birth weight or gestational age. The study focused on the therapy needed during the transport to the regional pediatric cardiology center. The obtained results proved that newborns with a prenatal diagnosis of CHD required less inotropic support and mechanical ventilation during transport. In ductal-dependent congenital malformations initiation of Prostaglandin E1 therapy was carried out later, thus higher doses being necessary in the case of newborns with postnatal diagnosis. The survival rate at the age of 1 year was somewhat similar in both study groups. Antenatal diagnosis of hypoplastic left heart syndrome was the most frequent cardiac pathology. Therapeutic approach, duration of mechanical ventilation, administration of Prostaglandin E1, as well as need for inotropic support were similar in both study groups. The duration of hospitalization and the survival rate were almost equal. As well as therapeutic approach, it was found that the need for nitric oxide (NO) was significantly higher among newborns with transposition of large vessels detected postnatally [In the study conducted by Gorla et al., in which over 300 patients diagnosed with complex heart malformations were enrolled, the prenatal detection rate was over 60%, with a gradual increase among conotruncal malformations . A similThe management of the newborn with congenital heart malformation is a complex one. These patients are in need of fluid resuscitation, inotropic and respiratory support, as well as correction of arrhythmias or coagulation disorders and selective therapy for any associated infections. The administration of prostaglandin E1 in ductal-dependent congenital malformations is crucial since its role is maintaining the permeability of the ductus arteriosus until the moment of corrective surgery. Extracorporeal life support (ECMO) is part of the therapy of the critically ill patient diagnosed with congenital heart malformation, providing support when the myocardial function is temporarily impaired. Even if the prenatal detection rate has increased significantly, the results obtained regarding the mortality rate and the complexity of preoperative morbidities are contradictory. Although in some studies there was no decrease in mortality among newborns with prenatal diagnosis, among those with ductal-dependent structural defects, a decrease in morbidity was observed in the preoperative period. Thus, mechanical ventilation, antibiotic therapy or inotropic support were less often approached as therapy, in newborns with prenatal diagnosis. Liver and kidney dysfunctions, as well as acidotic metabolic disorders were less often detected in the preoperative period among those with prenatal suspicion of heart defect. ,11The morbidity generated by congenital heart malformations and the influence of prenatal diagnosis on them are extremely important. Bonnet et al. demonstrated the fact that attention must be directed to the degree and severity of associated morbidities, considering that mortality is not influenced by prenatal diagnosis . From hiThe study of Levey et al. was also a retrospective one, carried out over a period of 4 years, the degree of prenatal detection being 68%. The results obtained by them, regarding the benefits of prenatal diagnosis are uncertain. Their study found that ductal-dependent cardiac malformations, such as univentricular heart were more frequently detected in the prenatal period. The group with prenatal diagnosis required less invasive ventilatory support, antibiotic therapy, cardiac catheterization or corrective intervention in emergency conditions . RegardiPrenatal diagnosis significantly changed the timing of surgical intervention, which was carried out earlier ,17. EarlThe same notable results were recorded following the introduction of regional screening programs in Sweden where there was an increase in the prenatal detection rate of heart malformations from 13.8% in 2009 to 56% in 2016 . PrenataThe study carried out by Quartermain included over 10,000 newborns who required surgical intervention in over 100 medical centers. The results obtained showed that those with prenatal diagnosis had fewer major risk factors .In the study of Suard et al., carried out over a period of 4 years, the overall prenatal detection rate was 71.5%. With regard to the diagnosed pathology, transposition of the great arteries had a detection rate of 80%, coarctations of the aorta represented a proportion of 56%, and total aberrant pulmonary venous drainage was detected in a percentage of 20%. This study also did not report any benefit of echocardiographic screening in terms of mortality .Sometimes the limited acoustic window restricts the contribution of fetal echocardiography, which is why additional methods of prenatal diagnosis are needed. In borderline cases, the fetal MRI evaluation brings additional information in order to establish the subsequent therapeutic attitude, including timing and type of birth, as well as evolution in the early neonatal period .The difference in results of the various studies can be partly explained by the type and length of each research, most being retrospective ones, as well as other factors such as pregnancy-associated pathologies, timing and operative technique, and neonatal intensive care unit level.Prenatal diagnosis in critical malformations such as hypoplastic left heart syndrome, transposition of great arteries and totally aberrant pulmonary venous drainage has proven its usefulness, allowing an early surgical intervention, thus ensuring improved neurological development. Sharing the experience and results obtained by each individual therapeutic center will definitely lead to drawing clear conclusions regarding the clinical contribution of congenital heart malformations prenatal detection. Even if mortality is an indicator somewhat unaffected by the degree of prenatal detection, this is still somewhat subjective, considering the fact that most critical ductal-dependent malformations with insidious evolution are now detected in the intrauterine period. The differences in reporting suggest the persistence of unequal access to medical services and the use of different protocols regarding the risk of structural heart defects in the fetus.