The Fontan operation represents the final stage of a series of palliative surgical procedures for children born with complex congenital heart disease, where a “usual” biventricular physiology cannot be restored. The palliation results in the direct connection of the systemic venous returns to the pulmonary arterial circulation without an interposed ventricle. In this unique physiology, systemic venous hypertension and intrathoracic pressures changes due to respiratory mechanics play the main role for propelling blood through the pulmonary vasculature. Although the Fontan operation has dramatically improved survival in patients with a single ventricle congenital heart disease, significant morbidity is still a concern. Patients with Fontan physiology are in fact suffering from a multitude of complications mainly due to the increased systemic venous pressure. Consequently, these patients need close clinical and imaging monitoring, where cardiac exams play a key role. In this article, we review the main cardiac imaging modalities available, summarizing their main strengths and limitations in this peculiar setting. The main purpose is to provide a practical approach for all clinicians involved in the care of these patients, even for those less experienced in cardiac imaging. The Fontan operation represents the final stage of a series of palliative surgical procedures for children born with complex congenital heart disease, where a “usual” biventricular physiology cannot be restored . Unlike Although the Fontan operation has dramatically improved survival in patients with a single ventricle congenital heart disease –8, signiChronic elevation of systemic venous pressure, required to maintain transpulmonary blood flow, leads to a multitude of complications. Furthermore, these patients experience a decreased exercise capacity due to chronic low cardiac output as a consequence of inability to adequately increase it during exercise mainly because of chronotropic incompetence .In addition, as a consequence of improved survival of these patients, the incidence of the so-called “Failing Fontan” is increasing. The “Failing Fontan” is a status characterized by progressive clinical deterioration and reduced health-related quality of life . MultiorDue to these significant possible complications, patients who undergo the Fontan procedure need close clinical and imaging monitoring, where cardiac exams play a key role , 13.The aim of this review is to highlight the information that can be obtained with each imaging modality and to illustrate their weaknesses in this peculiar setting.Nearly 10% of congenital heart defects belong to the group of functionally univentricular hearts . This coThe Fontan operation represents the final surgical stage in the strategy of palliation for the management of patients born with an anatomical or functional univentricular heart .The idea behind this palliation is to use the only ventricle available to sustain the systemic circulation by connecting it to the aorta, while ensuring an acceptable blood flow into the lungs in a passive way, without any additional propelling source, by connecting directly the systemic veins to the pulmonary arteries. The major advantage of this strategy is the separation between the systemic and pulmonary circulation with normalization of oxygen saturation.Since the original description  in the eCurrently, TCPC is achieved by a multistage surgical approach where the Fontan operation represents the last step.In early life, the goal of the initial surgical operation (first step) is to allow for survival, providing an unobstructed systemic outlet and a controlled pulmonary blood flow. Later, total cavopulmonary connection is usually achieved using a two-stage operation. A superior cavopulmonary connection (the superior vena cava is anastomosed to the pulmonary arteries) is performed at about 6 months of age (second step). The patient remains cyanotic after this stage, because desaturated blood flow coming from the inferior caval vein is still directed to the main ventricle and then to the aorta, but ventricle loading is significantly decreased. Total cavopulmonary connection (third and last step) is performed ordinarily between 3 and 5 years of age , connecting the inferior vena cava to the pulmonary arteries, usually by interposition of an extracardiac conduit. This leads to complete separation of the systemic and pulmonary circulations and to normalization of oxygen saturation.In patients at high risk of system failure due to small pulmonary arteries or ventricular dysfunction, a little communication (fenestration) between the extracardiac conduit and the systemic atrium can be created, allowing a protective “right-to-left shunt”, which limits systemic venous congestion, increases ventricular preload and output, with the unavoidable drawback of some degree of arterial desaturation . Later, Although when assessing long-term results of the Fontan operation several confounding factors may occur in relation to the different underlying defects and to the evolution of surgical management, long term follow-up data indicates that this operation has incredibly improved survival in patients born with “functionally univentricular hearts”. Without surgery, these patients only had a 10% chance of survival beyond the first year of life , whilst Therefore, nowadays the main issue in these patients is the significant morbidity consequent to the Fontan operation. Several complications occur late after surgery, and are almost unavoidable, mainly due to the systemic venous hypertension required to propel blood into the system . PotentiWith the “Classic Fontan” operation, where the right atrium was incorporated in the Fontan circulation, progressive atrial dilatation was a major issue, causing atrial arrhythmias and thromboembolic events. The incidence of these adverse events has been significantly reduced by the evolution of the surgical technique. Nevertheless, arrhytmias can still occur even with TCPC, in particular supraventricular tachycardia, which is more frequent with the aging of patients and may negatively affect the hemodynamics of the Fontan circulation, also predisposing to thrombotic events. The main mechanism of formation are atrial re-entry microcircuits  which caThromboembolic events can also occur and remain one the main causes of death in this setting . PredispThe increased systemic venous pressure leads to elevated pressure and congestion in the hepatic veins as well, causing pathological changes in the liver. Congestion, dilation of bile ducts, fibrosis, and cirrhosis can occur, exposing these patients even to liver malignancy , 22.Additionally, the increased central venous pressure may induce recanalization of embryologically preformed and obliterated vessels, with the development of systemic to pulmonary venous collaterals that can lead to systemic desaturation and worsening of ventricular function .The elevated pressure in the superior vena cava is transmitted to the thoracic duct as well, leading to impaired and abnormal lymphatic drainage, which can cause two rare but extremely dangerous complications: PLE and plastic bronchitis. Leakage into the intestine causes PLE, which represents the most frequent lymphatic problem in this setting . PLE impMoreover, over time the systemic ventricle may develop systolic and/or diastolic dysfunction because of the abnormal hemodynamic condition and ventricular morphology . VentricIn a patient who underwent the Fontan operation, routine follow up must check that the palliation system is working properly. Early signals of failing should be promptly detected by imaging, both for planning a circuit optimization if possible and to lead to an early transplant listing when perfectioning can not be achieved.The main goals of a comprehensive assessment are the ventricle and atrioventricular valve function, the patency of the Fontan pathway , and the presence of collateral flow . Ruling The different modalities have have their own strengths and weaknesses  and theyEchocardiography (ECHO) is the most used imaging modality in patients with congenital heart disease. It is an unequaled image modality in terms of availability, cost and ease of use, being possible even at the patient's bedside.Therefore, it remains the first-line imaging modality even in this peculiar setting .Nevertheless, as patients grow into adulthood, image quality is often limited due to diminishing acoustic windows. Multiple factors may be implicated, such as higher BMIs and chest wall deformity, particularly in patients who underwent multiple cardiac surgical operations . As a coFontan pathway and pulmonary arteries may sometimes be visualized in case of good acoustic windows. Nevertheless, CCT or CMR should be performed to rule out any issues with certainty, allowing for unrestricted visualization of all structures .Regarding ventricular function, it is well known that single ventricle function is not easy to assess, particularly when the single ventricle is a morphologic right ventricle. Agreement between echocardiographic and CMR evaluation of systolic function improves with experience in this setting but remains suboptimal. Especially when used as a test for assessing poor RV function, ECHO shows a high sensitivity, but specificity is heavily influenced by operator experience, with the risk of a relatively high rate of false positives . RegardiAtrio-Ventricular (AV) valve regurgitation is a common long-term complication in single ventricle circulation and ECHO remains the main imaging modality to routinely investigate valvar function. It can be performed using several imaging and Doppler parameters such as regurgitation jet area, vena contracta width, in addition to qualitative jet assessment .In summary, ECHO remains the first line imaging and a reliable method for systolic ventricular function  and valvCardiovascular Magnetic Resonance (CMR) is the only method able to simultaneously obtain a comprehensive anatomical and functional assessment.The advantages of this imaging modality are well recognized: the lack of invasiveness and ionizing radiation, the ability to visualize the entire cardio-thoracic anatomy with high spatial resolution and without acoustic window limitations, the opportunity to obtain hemodynamic and functional information thanks to the assessment of flows in any target vessel and to the accurate quantification of ventricular function . ExcelleHowever, CMR also has some drawbacks, mainly represented by the long scanning times, which necessitate general anesthesia in uncooperative patients (such as under 7–8 years of age) and make the exam difficult to perform in clinically unwell subjects. In addition, image quality can be limited by arrhythmia and CMR is not suitable in patients suffering from claustrophobia and in the presence of unsafe metallic devices .The entire cardio-thoracic anatomy is well depicted with contrast-enhanced magnetic resonance angiogram (MRA) and with non-contrast ECG-gated 3D sequences. Also, cine bright-blood sequences offer a good representation of vascular anatomy thanks to high blood-tissue contrast and dynamic visualization of vessels during the cardiac cycle , 2. BlacThe Fontan pathway and branch pulmonary arteries (PAs) are carefully evaluated to rule out stenoses that could be detrimental to flow dynamics in a circulatory system without a subpulmonary pump. Central PAs can be compressed and stretched by vessel roots and neo-aorta dilatation after the Norwood operation. Residual/recurrent coarctation of the aorta after aortic arch reconstruction is another complication that occurs in these patients and can promote ventricular hypertrophy and dysfunction. Pulmonary vein compression can be harmful to passive pulmonary flow circulation and need to be excluded, especially in patients with enlarged right atrium after atriopulmonary Fontan.CMR is the gold standard for the assessment of ventricular size and function in univentricular hearts  regardleAlthough a normal reference range for ventricular volumes in UVH has not been universally defined, serial assessment of ventricular dimensions is important because dilatation of systemic ventricle is an independent risk factor for death and transplant after Fontan palliation , and echTissue characterization with late gadolinium enhancement technique allows to identify the presence and extent of myocardial fibrosis, which correlates with decreased ventricular function, increased EDVi and incidence of ventricular tachyarrhythmia .Vessel flow analysis is routinely performed with conventional through-plane 2D phase-contrast (PC) sequences. PC can be used to assess cardiac index, calculate semilunar valve regurgitation by direct quantification or estimate atrioventricular valve regurgitation by matching antegrade systemic flow and ventricular stroke volume. Hemodynamic magnitude of a unilateral branch pulmonary artery stenosis can be evaluated by calculating disproportion of pulmonary blood flow distribution.Flow analysis includes quantification of systemic-to-pulmonary collaterals. Elevation of central venous pressure promotes development of veno-venous collaterals which arise from superior or inferior vena cava and innominate veins, and connect to pulmonary veins or directly to the atria, thus bypassing pulmonary vascular bed with consequent cyanosis.Aorto-pulmonary collaterals (APCs) are a response to systemic desaturation: they originate from systemic arteries (descending aorta and its branches), and supply the pulmonary circulation with high pressure flow which compete and limit deoxygenated blood flow from cavo-pulmonary connection. APCs also represent a right-to-left shunt and contribute to ventricular volume overload . With PCFontan-associated liver disease (FALD) represents a major non-cardiac determinant of mortality following the Fontan procedure and an emerging concern in patients with univentricular pathophysiology. Hemodynamic changes with elevated central venous pressure and diminished cardiac output promote congestive hepatopathy, resulting in progressive fibrosis/cirrhosis in response to chronic liver injury, with multiple regenerative nodules which may finally degenerate to hepatocellular carcinoma. The staging and surveillance of liver fibrosis in FALD requires a multi-modality approach, including radiological imaging. US elastography is a valuable screening investigation in identifying features of FALD and may be useful in identifying progression of FALD before biochemical hepatic dysfunction. Both magnetic resonance imaging and computed tomography provide more detailed information in delineating liver injury in FALD , and areIncreased systemic venous pressure is also associated with impaired lymphatic drainage and engorgement of the lymphatic system. Patients with lymphatic perfusion abnormalities develop significant more early and late complications after Fontan completion, even in the absence of obstruction in the Fontan pathway or ventricular dysfunction. Various manifestations can occur such as protein losing enteropathy (PLE), plastic bronchitis (PB), interstitial pulmonary edema, pleuro-pericardial effusion and ascites.PLE and PB are among the most serious complications that can occur late after Fontan Palliation. MR is able to characterize lymphatic perfusion abnormalities using static and dynamic sequences . HeavilyDynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) is a recently developed technique which allows a minimally invasive evaluation of the lymphatic flow pathways and their anomalies, using time-resolved MR angiography sequence after intranodal injection of gadolinium-based contrast material . DCMRL dCardiac Computed Tomography (CCT) is an alternative imaging modality to assess Fontan anatomy and ventricular function when CMR is contraindicated or in specific clinical conditions such as unstable and uncooperative patients, stent evaluation and acute setting . Thanks CCT scan in this setting can be challenging to perform. The main issue in evaluating these patients is to obtain a uniform opacification of the venous pathway and the pulmonary arteries. Typically, blood flow from the superior vena cava is directed to right lung, whereas flow from the inferior vena cava is mostly directed to the left lung. The result is a different timing of opacification of the caval veins and the pulmonary arteries. Hence, conventional contrast administration into the upper arms and first pass through the SVC and PAs generates streak artifacts and pseudo-filling defects which can mimic thrombosis . VariousA systemic arterial phase acquisition is generally indicated for coronary artery imaging or when functional assessment is requested . VolumetAssessment of vascular stents  represenIn recent years, the use of cardiac catheterization as diagnostic imaging modality has significantly decreased, because of the advent of new non-invasive advanced imaging techniques, such as CCT and CMR.Nevertheless, catheterization remains crucial when the likelihood of an intervention for circuit optimization is high and when specific hemodynamic parameters are needed, such as assessment of PVR, ventricular diastolic function (including constrictive and restrictive physiology) and pressure gradients .Cardiac catheterization is the only method able to accurately measure end diastolic ventricular pressure, Fontan system pressure and transpulmonary gradient . In addiAs catheter evaluation of estimated flows using the Fick principle and assumed oxygen consumption is limited and potentially incorrect , combineCardiac catheterization can perform treatment at almost any levels of the Fontan system, , with angioplasty or stent placement. It is also possible to percutaneously close (if no longer needed) or create (in failing systems) a fenestration . If signLymphangiography could play an important role in case of complications with a suspected lymphatic etiopathology such as protein-losing enteropathy or plastic bronchitis. Some high-volume centers are developing techniques for embolizing these periportal/peritracheal dilated lymphatic vessels with good results .In summary, the main strengths of cardiac catheterization are the possibility of intracavitary pressure measurement and the possibility of interventions during the same procedure if needed. The main drawbacks include the invasive nature often requiring anesthesia or sedation, ionizing radiation exposure and contrast nephrotoxicity. Recent ESC GUCH Guidelines recommend Cardiac catheterization at a low threshold in cases of unexplained oedema, exercise deterioration, new-onset arrhythmia, cyanosis, and haemoptysis .Patients with Fontan physiology suffer from a multitude of unavoidable complications mainly due to the increased systemic venous pressure. Consequently, these patients need close clinical and imaging monitoring, since early recognition of failing hemodynamics can be essential to secure long-term survival.ECHO remains the first-line method, and is mainly used for routine follow-up.Nevertheless, nowadays cross-sectional imaging has become an essential tool in the evaluation of these patients. CMR in particular has acquired a key role in providing anatomic and functional information at the same time, overcoming the limitations of poor acoustic ECHO windows as patients become adults. CMR is also able to provide essential information about extra-cardiac complications such as liver dysfunction and abnormal lymphatic drainage. CCT may be useful when CMR is contraindicated or for anatomical assessment in uncooperative patients. Cardiac catheterization is currently reserved for measuring specific hemodynamic parameters and for those patients where an intervention during the same procedure is expected.PCil, LG, and AS contributed to conception of the review. PCia, MC, VB, DC, PG, MP, PB, and VL wrote sections of the manuscript. PCil wrote the first draft of the manuscript. All authors contributed to manuscript revision, read, 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.


We sought to objectively assess left ventricular myocardial work (MW) parameters after right ventricular septal pacing (VSP) and His-Purkinje system area pacing (HPSAP) procedures.Patients undergoing double-chamber pacemaker implantation for III-degree atrioventricular block (III° AVB) were assessed 1 year after implantation. VSP and HPSAP groups  were compared against 40 healthy age-matched volunteers. Two-dimensional ultrasound speckle tracking imaging was used to obtain the global myocardial work index (GWI), global myocardial work efficiency (GWE), global myocardial constructive work (GCW), global myocardial wasted work (GWW), left ventricular stratified strain, and peak strain dispersion (PSD).p < 0.05). HPSAP outperformed the VSP group in comparisons of global left ventricular longitudinal strain and stratified strain. Compared to controls, the GCW of all segmental myocardium (17/17 segments) in the VSP group was significantly reduced, while 70.59% (12/17 segments) in the HPSAP group was lower than the control group. GCW in the left ventricular segment of the HPSAP group was bigger than the VSP group  and mainly concentrated in the ventricular septum and inferior wall.GWI, GWE, and GCW parameters were improved in HPSAP compared to VSP, while GWW was significantly larger in the VSP group compared to the HPSAP group (all Our findings suggest that HPSAP performance outcomes are improved over VSP after 1 year, especially in left ventricular contractile synchrony, and HPSAP is beneficial to the effective myocardial work of the left ventricle. Previous studies have shown that different cardiac pacing methods can lead to reduced left ventricular systolic and diastolic function . With thThe aim of this study was to physiologically compare the two clinical cardiac pacing therapies using objective evaluation indexes. Here, myocardial work was assessed using a visual quantitative evaluation of the pressure-strain ring derived from ultrasonic speckle tracking imaging technology.The following were the judgment criteria for successful pacing using the left His-Purkinje system: (1) Pacing QRS width significantly narrowed (<120 ms); (2) V1 lead tip unipolar pacing QRS wave in the Qr/QR/qr form; (3) Pacemaker R wave time to peak of V5 lead  <80 ms; (4) It was not required from the electrogram that the beam branch potential be seen in the cavity or whether the SV interval . The security range criteria to judge electrode tip depth involved the following: (1) Intraoperative immediate tip unipolar pacing impedance from 700 to 1,200Ω, ring unipolar impedance <tip unipolar impedance or ring unipolar impedance <2,000Ω; (2) Tip monopole pacing threshold <1.0 V/0.4 ms, tip monopole pacing threshold <ring monopole pacing threshold. After meeting these criteria, the C315-His sheath tube was removed with a special incision and the wire was fixed. Before inclusion in the HPSAP study group, the pacing location was verified by a transthoracic echocardiogram (TTE).Alternatively, the VSP wire implantation process involved placing a 7F sheath through the axillary vein under the guidance of the guide wire and inserting a 58 cm active electrode wire along the sheath to the inferior vena cava. The electrode wire was then adjusted to the right ventricular septum under the support of a plastic inner core wire. The relationship among the wire, tricuspid ring, anterior interventricular groove, and cardiac apex was evaluated through right anterior oblique fluoroscopy. The angular relationship between the end of the wire and the ventricular septum was observed through the left anterior oblique fluoroscopy. After determining the position of the wire under fluoroscopy, the electrode wire screw head was fixed to the right ventricular surface of the interventricular septum, and the plastic inner core wire was extracted. Since there was no obvious clinical difference, no requirement was made for high, middle, and low interventricular septum placement. The test electrode parameter evaluation criteria involved bipolar pacing impedance ranging from 400 to 1,000Ω, bipolar pacing threshold of 1.0 V/0.4 ms or less, bipolar perceptual of 5.0 mV or greater, and the damage current was visible in the far field of the cavity. Afterward, the sheath was removed and the wire was fixed.The study was approved by the Institutional Review Board of Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital.We retrospectively identified patients who received atrioventricular pacemaker implantation (DDDR pacemaker) in the Cardiovascular Division of our hospital from February 2018 to September 2019. According to the inclusion and exclusion criteria, patients meeting the requirements were screened periluminally, and arrangements were made for echocardiography at our hospital 1 year after implantation.Inclusion criteria: Pacemaker implantation in patients with III° AVB. Before pacemaker implantation, LVEF was within the normal range (55% < LVEF < 80%). Exclusion criteria: 1. Complicated arrhythmia; 2. LVEF decreased (LVEF < 55%); 3. Aortic stenosis or moderate or above reflux; and 4. Complicated hypertension, kidney disease, and cardiomyopathy. Additionally, the pacemaker programming method of patients enrolled in the case group should meet the following criteria. (1) Subjects with continuous ventricular pacing dependence after implantation were excluded. Double-chamber permanent pacemaker implantation patients with a preoperative diagnosis of III° AVB were included, and the proportion of ventricular pacing (VP) was confirmed to be greater than 95% between the last follow-up and the date of test by the programmed pacemaker. (2) To ensure that the subject’s ventricular excitement does not bypass its own atrial-ventricular transmission fusion, the programmed pacemaker was set to 350 ms without its own atrial-ventricular transmission after PAV and SAV (the pacemaker was in the state of VP). (3) After the aforementioned verification, to unify the subjects’ AV interphase, the AV interphase was adjusted to PAV/SAV 160/120 (MS). (4) The pacing QRS width of the subjects in ventricular pacing state was measured and recorded manually. The measurement method employed was the lead with the widest QRS wave in the subject’s standard 12-lead electrocardiogram. Before inclusion in the HPSAP group, the pacing position was verified by TTE .According to the criteria, a total of 43 patients were collected and divided into the following categories according to the method of pacemaker implantation. A total of 20 patients were included in the VSP group, comprising 15 men and 5 women ranging from 52 to 80 years old . In the HPSAP group, there were 23 patients, comprising 20 men and 3 women, aged from 55 to 78 years (72.4 ± 4.0). As control group subjects, 40 volunteers with no abnormalities in biochemistry, ECG, and or cardiac ultrasound examination were selected, including 30 men and 10 women, aged from 54 to 77 years (64.3 ± 10.5).For this study, the HPSAP wire implantation process involved inserting a C315-His sheath tube (Medtronic) and 3,830 electrode wire (Medtronic) through the axillary vein. After connecting a polyconductive physiological recorder, His bundle potentials were plotted at the base of the right ventricular septum, and the sheath tube and electrode wires were gradually moved along the line from the H wave to the apex of the heart, reaching the middle and far sections of the His bundle . The QRS waveform of the leading V1 in the right ventricular myocardium was typical of the “W” type. To position the electrode, the angle between the sheath tube and the septum and the length of the electrode sheath tube was adjusted before preliminary testing of the pacing threshold and impedance. The sheath tube was fixed, and the head end of the 3,830 electrode conductor was rotated clockwise to enter the septum under perspective observation. To comprehensively position the screw-in depth, X-ray location from different angles, pacing QRS wave morphology, and pacing impedance measures were used. In some cases, a contrast agent was injected through the sheath tube to observe the electrode screw-in depth.Blood pressure data were collected from study subjects in a calm state using a cuff and brachial artery pressure measurements of the left arm. The mean value was recorded after three measures. Cardiovascular imaging was performed using a GE Vivid E9 ultrasonic diagnostic instrument fitted with an M5S probe and used at a frequency of 1.5–4.6 MHz, or the 4 V probe at a frequency of 1.5–4.0 MHz. Image analysis was undertaken using the EchoPAC workstation. Conventional synchronous electrocardiogram measurements were taken from patients in the left lateral recumbent position using the M5S probe to evaluate left ventricular function and blood flow at each flap. Switching to the 4 V probe and with patients holding their breath, tri-plane measurements were used to obtain two-dimensional grayer dynamic map storage of the four cavities, three cavities, and two cavities of the standard apex of three cardiac cycles. Images were then collected and stored in the “4D” mode to ensure that the inner and outer membranes of the left ventricle were within the ultrasonic sector and the frame frequency adjusted to more than 40% of the heart rate.Images were imported into the EchoPAC workstation (version 203), and the opening and closing time of “AV” and “MV” was determined. Three dynamic grayscale images were selected, and the endocardial surface was drawn automatically or manually. After acquiring the 17-segment strain time curve, myocardial work parameters were calculated, including GWI, GWE, GCW, and GWW of the myocardium at the same cardiac cycle . Other pp < 0.05 considered to be statistically significant.Measurement data conforming to a normal distribution were adopted (p < 0.05). No other statistically significant differences were found for other parameters within groups , respectively. Whereas for GWW, the findings were VSP group > HPSAP group > control group (p < 0.05). Comparing the global and stratified longitudinal strain of the apical four, two, and three chambers, we found the control group > HPSAP group > VSP group , while 70.59% (12/17 segments) of the HPSAP group was lower than the control group (p < 0.05). GCW measures in 29.41% (5/17 segments) of the HPSAP group were bigger than the VSP group (p < 0.05) and mainly concentrated in the ventricular septum and inferior wall  in the VSP group was significantly reduced  using His bundle pacing can reproduce real physiological pacing in patients , 6. AlthIn 2017, Huang Jianwei’s team described the left bundle branch pacing technology under the intima of the left ventricle , which pHere, the pressure-strain ring parameter proposed by Russell et al.  was usedOther scholars  have repWork distribution evaluation allows clinicians to better evaluate ischemic patients and select CRT candidates. Furthermore, it provides valuable additional information on left ventricular function in patients after CRT , 24. In A previous report by Mafi-Rad et al.  found thFinally, we must consider some of the limitations and future improvements of our study. Although there were no gender or age-related changes among the patient groups, there were differences in diastolic blood pressure. However, on the basis of reported findings by Russell et al., only GWI and GCW are significantly associated with systolic blood pressure. Other considerations include the following: (1) Although all enrolled patients with III° AVB were implanted with pacemakers, their health was complicated by various diseases, with a small number of patients with hypertension; (2) Further confirmation of our findings is warranted through increasing the sample size and refining the patient groups studied; (3) Image quality effects may potentially affect the research results; and (4) The follow-up time for studying the His-Purkinje system area pacing was limited.This study confirms that CRT with HPSAP enables the left ventricular myocardium to work more harmonically and efficiently than VSP, at least within 1 year of follow-up. We plan to use the new ultrasound technology more extensively by enrolling more pacing cases and extending the follow-up to the medium and long term. Increasing the sample size and observation period will provide a more objective basis for selecting clinical pacing treatments.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 Sichuan Provincial People’s Hospital Ethics Committee. The patients/participants provided their written informed consent to participate in this study.YL, YT, and QM contributed to the conception of the study. QM and YL performed the experiment. YD and CL contributed significantly to analysis and manuscript preparation. QM and SW performed the data analyses and wrote the manuscript. TF, HX, JL, XL, and ZG helped perform the analysis with constructive discussions. All authors contributed to the article and approved the submitted version.


Rare cardiovascular diseases (RCDs) have low incidence but major clinical impact. RCDs’ classification includes Class I—systemic circulation, Class II—pulmonary circulation, Class III—cardiomyopathies, Class IV—congenital cardiovascular diseases (CVD), Class V—cardiac tumors and CVD in malignancy, Class VI—cardiac arrhythmogenic disorders, Class VII—CVD in pregnancy, Class VIII—unclassified rare CVD. Cardiovascular Magnetic Resonance (CMR) is useful in the diagnosis/management of RCDs, as it performs angiography, function, perfusion, and tissue characterization in the same examination. Edema expressed as a high signal in STIRT2 or increased T2 mapping is common in acute/active inflammatory states. Diffuse subendocardial fibrosis, expressed as diffuse late gadolinium enhancement (LGE), is characteristic of microvascular disease as in systemic sclerosis, small vessel vasculitis, cardiac amyloidosis, and metabolic disorders. Replacement fibrosis, expressed as LGE, in the inferolateral wall of the left ventricle (LV) is typical of neuromuscular disorders. Patchy LGE with concurrent edema is typical of myocarditis, irrespective of the cause. Cardiac hypertrophy is characteristic in hypertrophic cardiomyopathy (HCM), cardiac amyloidosis (CA) and Anderson–Fabry Disease (AFD), but LGE is located in the IVS, subendocardium and lateral wall in HCM, CA and AFD, respectively. Native T1 mapping is increased in HCM and CA and reduced in AFD. Magnetic resonance angiography provides information on aortopathies, such as Marfan, Turner syndrome and Takayasu vasculitis. LGE in the right ventricle is the typical finding of ARVC, but it may involve LV, leading to the diagnosis of arrhythmogenic cardiomyopathy. Tissue changes in RCDs may be detected only through parametric imaging indices. The commonly accepted prevalence of rare diseases is less than 1 per 2000 in the general population . LG. LGT1-weMyocardial infarction is characterized by subendocardial or transmural LGE in the distribution of epicardial coronary arteries. Subepicardial or patchy LGE usually in the inferolateral wall is characteristic of myocarditis. Finally, diffuse subendocardial LGE that does not follow the typical distribution of epicardial coronary arteries is often associated with microvascular coronary artery disease, vasculitis, antiphospholipid syndrome, and endocrine disorders, such as Cushing syndrome and autoimmune thyroid disease .(b) T2-weighted images (T2-W): T2-W images result from water accumulation, due to edema ..95].CMR is also of value in the detection of intracardiac thrombi. Usually, the majority of thrombi is small, homogeneous, often associated with venous catheters and typically hypointense on first-pass perfusion, due to lack of vasculature . CompareFinally, CMR is of great value in the evaluation of cardiotoxic effects, due to chemotherapy used in various oncologic diseases. In this context, early detection of cardiotoxicity is crucial and presents an opportunity for personalized risk stratification and early therapeutic intervention before irreversible heart failure occurs. CMR is superior to echocardiography for detecting subclinical declines in LVEF early after cardiotoxic therapy. Even when applying 3D-TTE techniques, which demonstrated less variability, this methodology lacked the desired accuracy to reliably identify subtle 5% changes in LVEF that may have major management implications .Tissue characterization using parametric pixel-wise T1 and T2 mapping is extremely useful in detecting subtle myocardial inflammatory changes and has been validated in a variety of systemic conditions, including the diagnosis of myocarditis. Additionally, the measurement of ECV has also shown significant promise as a surrogate marker for diffuse myocardial fibrosis, overcoming the limitations of LGE in this regard. An expanded ECV is associated with adverse outcomes in large patient cohorts .Finally, immune checkpoint inhibitor (ICI)-induced cardiotoxicity is a rare immune-related adverse event (irAE) characterized by a high mortality rate. The diagnosis of ICI-induced cardiotoxicity can be challenging, and CMR is the diagnostic tool of choice in clinically stable patients with suspected myocarditis .Class VI includes cardiac arrhythmogenic disorders.Arrhythmogenic cardiomyopathy (ACM) is an emerging new concept of a life-threatening heart muscle disorder, due not only to desmosome gene mutations, but also to non-desmosome genes, such as filamin C, lamin A/C, phospholamban, transmembrane protein 43, titin, SCN5A, and RNA binding motif protein 20. CMR is the gold standard for evaluating left and right ventricular structure/function, edema, and fibrosis. The identification of regional fibrosis with LGE has prognostic value. In ACM patients with only mild LV dysfunction but with evidence of phospholamban, filamin C or lamin A/C mutations, an ICD is considered a reasonable approach .Fibro-fatty myocardial replacement is the diagnostic criterion of arrhythmogenic cardiomyopathy (ACM) that can affect both RV-LV. The 2010 International Task Force diagnostic criteria lacked specific criteria for the diagnosis of LV variants of ACM .“dominant-right” variant, i.e., the classic ARVC phenotype characterized by the predominant RV involvement, with no or minor LV abnormalities; (ii) the “biventricular disease” variant characterized by the parallel involvement of the RV and LV; and (iii) the “dominant-left” variant  characterized by the predominant LV involvement, with no or minor RV abnormalities. ALVC is a very rare non-ischemic cardiomyopathy. CMR shows that ALVC presents fibro-fatty replacement predominantly in the LV, impaired left ventricular systolic function and ventricular arrhythmias originating from the LV. ALVC with RV involvement has a worse prognosis [The current classification of ACM according to Padua criteria includes the following phenotypic variants: (i) the rognosis . We shourognosis . In contrognosis .The Padua criteria for diagnosis of ACM are based on a multi-parametric approach encompassing functional and structural ventricular abnormalities, tissue characterization findings, depolarization and repolarization electrocardiographic alterations and ventricular arrhythmias, and familial/genetic background which are grouped into 6 categories. The novelty of the Padua diagnostic criteria essentially consists of the introduction of tissue characterization by contrast-enhanced (CE-CMR) for the detection of fibro-fatty myocardial replacement of both ventricles and the addition of new ECG criteria, including depolarization/ repolarization abnormalities and ventricular arrhythmias, specific for the LV involvement.Class VII includes rare CVDs and disorders in pregnancy. Peripartum cardiomyopathy develops most frequently in the month pre- or post-partum, whereas DCM often is known already or develops in the second trimester. Mortality in peripartum cardiomyopathy varies from <2% to 50%. There are few reports on DCM and pregnancy, including only a limited number of patients. Ventricular arrhythmias, heart failure, stroke, and death occur in 39–60% of high-risk patients. However, patients with modest LV dysfunction tolerated pregnancy well. Previous studies on >700 pregnancies in 500 women with HCM showed a good prognosis, even though three deaths were reported in high-risk patients [patients . Complicpatients .Although echo is the first-line modality for assessing maternal cardiac status, CMR can provide information about cardiac anatomy/function in pregnant women with complex cardiac disease or suspected aortic pathology. Furthermore, LV remodeling during normal pregnancy is associated with myocardial hypertrophy without edema or diffuse fibrosis of the myocardium, or LV systolic dysfunction. These findings, observed in normal pregnancy, can serve as an important basis for identifying myocardial abnormalities in patients with peripartum cardiomyopathy and other pregnancy-related myocardial diseases .Class VIII includes unclassified rare cardiovascular diseases/disorders, such as isolated ventricular non-compaction (IVNC), characterized by prominent intra-ventricular trabeculations separated by deep intertrabecular recesses. Although microvascular dysfunction is known, myocardial infarction is rare and usually seen as a consequence of coincidental coronary artery disease [ disease . In thes disease .CMR can perform angiography, function, perfusion, and tissue characterization in the same examination;Evidence of edema expressed as a high signal in STIRT2 or increased absolute T2 values on T2 mapping is common in acute/active inflammatory states;Diffuse subendocardial fibrosis, expressed as diffuse, subendocardial LGE, is characteristic of microvascular disease, as in systemic sclerosis, small vessel vasculitis, anti-phospholipid syndrome, cardiac amyloidosis, and cardiac involvement in metabolic disorders;Replacement fibrosis, expressed as LGE, in the inferolateral wall of LV is common in neuromuscular disorders, such as DMD and BMD. However, other myocardial areas can be also involved;Active sarcoidosis can present with punched-out LGE with edema, irrespective of the cause and blood biomarkers;Cardiac hypertrophy is characteristic in HCM, CA and AFD, but LGE may be located in IVS, subendocardium and lateral wall in HCM, CA and AFD, respectively. Furthermore, increased absolute T1 values or T1 signal on T1 mapping are characteristic of HCM, CA, while reduced T1 signal on T1 mapping is characteristic of AFD;Magnetic resonance angiography provides non-invasive information in various aortopathies, such as in Marfan, Turner syndromes and Takayasu, giant cell, Cogan and Behcet vasculitis;LGE in RV is the typical finding of ARVC. However, LGE can be also found in LV leading to the diagnosis of ACM, according to new Padua criteria;The tissue changes in RCDs may be detected only through changes in parametric imaging indices, which include native T1, T2 mapping and ECV, while all other indices may be normal.RCDs have a low incidence, but their impact on the survival and quality of life of the affected patients and their families is of great importance. Recently, the new classification of RCDs allowed a better understanding of their pathophysiology. Cardiovascular imaging, and specifically CMR, plays a pivotal role in the diagnosis and risk stratification of these patients.CMR, due to its capability to perform anatomy, function, perfusion, angiography, and tissue characterization, is the ideal tool to screen RCDs and identify even the most subtle, subclinical changes in this special group of patients.


Reconstruction of the pulmonary artery associated with lobectomy for the radical resection of lung cancer is a safe and effective therapeutic option that may allow radical resection when lobectomy is not technically feasible, avoiding pneumonectomy. This review addresses some controversial aspects concerning the intraoperative and perioperative management of a sleeve resection with pulmonary artery reconstruction that may influence the outcome. Pulmonary artery reconstruction associated with lobectomy is a safe and viable parenchymal sparing intervention to radically treat lung cancer, allowing better long-term survival, lower perioperative morbidity and mortality rates and functional benefits if compared with PN.Reconstruction of the pulmonary artery (PA) associated with lobectomy for the radical resection of lung cancer has been progressively gaining diffusion in lung cancer surgery as a safe and effective therapeutic option that may allow radical resection when lobectomy is not technically feasible, avoiding pneumonectomy. There are some controversial aspects concerning the intraoperative and perioperative management of a sleeve resection with PA reconstruction that may influence the outcome. In the present article, the authors have analyzed some of the main technical and oncological aspects to take stock of what they have learned from their lung-sparing operations experience over time. PA reconstruction may require prosthetic materials including different options with variable cost. A main concern in vascular reconstructive procedures is avoiding tension on the anastomosis. When PA reconstruction is required, appropriate anticoagulation management is crucial. Results from the main literature data confirm the reliability of lobectomy associated with PA reconstruction in terms of perioperative morbidity and long-term survival. Sleeve lobectomy and PA reconstruction can be performed safely and effectively even after induction therapy. Lobectomy combined with resection and reconstruction of the bronchus, pulmonary artery (PA), or both has been shown to be a viable option for the treatment of lung cancer in the past three decades ,2. In moThe first case of tangential resection and direct suture repair of the PA for lung cancer was reported by Allison in 1952 . Later, These surgical procedures may be necessary to avoid PN in patients with compromised heart and/or pulmonary function. However, the benefits of parenchymal preservation have been proved even in patients without cardiopulmonary impairment by recent studies ,9,10.Lobectomy associated with bronchial and vascular reconstruction presents higher technical difficulty than standard major lung resection, but recent experience suggests that these reconstructive interventions are associated with better overall survival, postoperative morbidity and mortality compared to PN ,14,15,16The indication for an SL and PA reconstruction for lung cancer is well defined: a primary tumor or N1 nodes infiltrating the origin of the lobar branches of the vessel but not as far as to make a PN unavoidable. Establishing the definitive indication for a reconstructive procedure of the PA may be not always possible preoperatively. The most appropriate diagnostic exam to identify the vascular involvement is the Computed Tomography (CT) scan with contrast medium. Angiography and Magnetic Resonance Imaging could add further details in order to better define the infiltration pattern. Nevertheless, the extension of the PA infiltration is not always clearly defined at preoperative imaging, and the definitive decision is made intraoperatively. Not infrequently, incongruities between radiological evidence and intraoperative findings, due to over- or underestimation of the vascular involvement by the CT scan, may lead to an incorrect indication.CT scan is also a valid diagnostic method to evaluate the nodal status of the disease. If enlarged mediastinal lymph nodes are found, histologic or cytologic assessment by mediastinoscopy or Trans-Bronchial Needle Aspiration (TBNA) is indicated. In case of N2 disease confirmation, induction therapy is indicated.When a bronchial or/and vascular infiltration is suspected, bronchoscopy is a mandatory preoperative examination to be performed by one of the operating surgeons in order to anticipate the intraoperative appearance of the airway. An eventual presence of bronchial wall compression may suggest peribronchial tumor infiltration. This is crucial information, especially for the anatomical areas where the PA is adjacent and potentially involved.If a bronchial reconstruction is performed, it is advisable to perform repeated bronchoscopies at the end of surgery, before discharge from the hospital, and during the follow-up period .The right and the left PAs can be involved to various longitudinal extents. This condition is crucial to assess the feasibility of a reconstructive procedure. Although contrast-enhanced CT scan is an effective tool to assess preoperatively the PA infiltration, this examination is generally not sufficient to correctly plan the vascular reconstructive procedure and to choose the appropriate technical option.A tangential resection with direct suture could be appropriate to achieve a radical resection when a very limited infiltration of the arterial wall is found at surgical exploration. The reconstruction can be performed using a patch , avoiding a circumferential resection for larger defects ensuing from a greater vascular involvement, up to 30% or 40% of the vessel circumference. A sleeve resection and reconstruction by an end-to-end anastomosis, or by the interposition of a prosthetic conduit is indicated for more extended infiltration.Thus, the reconstructive technique and the eventual choice of prosthetic material have to be decided intraoperatively in most cases.Postoperative quality of life has been considered one of the most important factors when making the decision to perform an SL rather than a PN. In a number of studies ,17, lungNonetheless, the decision to perform PN or SL is primarily made in order to obtain a complete (R0) resection, so considering both the oncological and physiological aspects. A large amount of clinical data prove that PN, particularly right PN, can be considered as a “disease itself”, with severe postoperative impairment of lung capacity, cardiac function, and quality of life. Thus, this intervention should be performed only when necessary to achieve a complete oncological resection.The first phase of the surgical procedure consists of accomplishing the complete dominion of the proximal portion of the PA. Even though division of the superior pulmonary vein can simplify the exposure of the PA, transection of this vessel should be deferred until becoming aware of the feasibility of the procedure. The resection step begins once the main and distal PA, the bronchus, and both pulmonary veins have been properly prepared. However, to obtain a complete tumor resection, PN can be unavoidable when extended infiltration of the PA is present, as in the condition of a left upper lobe tumor infiltrating the concave surface of the PA from its origin down to the anterior–basal artery or, on the right side, in the case of posterolateral infiltration at the level of the artery for the superior segment of the lower lobe.The adequateness of a limited tangential resection with a consequent direct suture for a minimal infiltration of the arterial wall has been reported by some authors .Lobectomy with “en bloc” PA resection and reconstruction by an end-to-end anastomosis, a patch, or prosthetic conduit is required for more extended neoplastic involvement of the vessel. Additionally, residual tumor or scarring tissue ensuing after induction therapy and involving the PA may require a sleeve resection.When performing a sleeve resection with anastomotic reconstruction, it is advisable to standardize the intraoperative strategy. Accomplishing full control of the PA is a key intent. The resection phase should start when the PA, bronchus, and pulmonary veins are properly isolated. Firstly, the superior pulmonary vein is divided. Generally, the anatomical distance of the pulmonary veins from the tumor makes their control less challenging. Nevertheless, on the left side, the tumor may involve the upper lobe bronchus and the anterior portion of the fissure. An intrapericaldial control of the superior pulmonary vein can be easily achieved. For the reconstructive phase, the dissection in the interlobar fissure is crucial, which is mainly on the left side. Clamping of the PA is then performed. A dose of 1500 Units of heparin sodium (instead of the dose between of 3000 and 5000 Units used in the past) is administered intravenously . AfterwaPatch reconstruction, end-to-end anastomosis or conduit interposition can be considered depending on the PA defect extent during the reconstructive phase. For all of the above-mentioned PA reconstruction procedures, running 5-0 monofilament nonabsorbable sutures are used ,23,24. APatch reconstruction is a very versatile technique and can be used in a variety of situations, ranging from moderate infiltration involving the origin of segmental arteries to significant defects extended longitudinally on one face of the PA. The opposite side of the circumference of the PA has to be free from tumor; otherwise, a sleeve resection with end-to-end anastomosis or conduit interposition is required. In order to reduce the arterial clamping time, vascular reconstruction is performed before the bronchial anastomosis, when necessary. After the partial resection, an oval defect oriented along the PA axis ensues, even if the resected portion is round. This is caused by the tension that the lower lobe produces on the vessel. It is advisable to tailor the patch on the resected vascular portion rather than on the PA defect . AlthougTo improve technical features of the autologous pericardium, the authors have devised and described in the past an intraoperative method of fixation of the patch by a glutaraldehyde-buffered solution . The gluWhen 50% or more of the PA circumference is infiltrated by the tumor, a sleeve resection is always mandatory. After the resection, frozen section histology on vascular margins should be always performed, and if tumor infiltration is still present, PN is required.When a bronchial anastomosis is associated, PA reconstruction is usually performed after its completion to minimize the manipulation of the vessel. Moreover, the exposure of the bronchial stumps is better when the artery is divided. Finally, after completion of the bronchial anastomosis, the tension on the vascular anastomosis is reduced because the bronchial axis is shortened. Technical issues regarding bronchial reconstruction after SL have been extensively reported in previous publications by the present authors ,20,21,22Regular and smooth margins  are desirable once dividing the artery, even at the expense of some loss of tissue. This can facilitate the proper placement of the stitches and adequate vascular stumps approximation. Furthermore, regular suture margins make the correction of the eventual caliber discrepancy easier. Due to the elasticity of the arterial wall, caliber discrepancy never represents a technical problem. By uplifting the lower lobe while suturing, the gap between the two arterial ends can be reduced. The posterior portion of the anastomosis is performed as a first reconstructive step. Afterwards, the anterior part of the suture (which is the simpler phase) is accomplished. Once the anastomosis has been completed, the suture is tied after removal of the distal clamp to restore backflow and to allow air drainage. Once the anastomotic suture is completed and before it is tied, the distal vascular clamp is partially opened, thus restoring the backflow and allowing air drainage within the untied portion of the suture line. The suture is then tied, and the arterial clamp is removed. Any residual tension is released by the restoration of blood flow and the removal of the proximal clamp. A prosthetic conduit implant is indicated when the gap between the arterial stumps is considered excessive. A 5-0 or 6-0 monofilament nonabsorbable material is used to perform the anastomotic running suture, placing stitches meticulously to avoid potential future stenosis. The end-to-end anastomosis can be technically more demanding in case of higher tension between the vascular stumps and caliber discrepancy .It is important to test the arterial axis and suture line after re-expansion of the residual lobe/lobes. Re-inflation of the lower lobe elevates the hilum, potentially determining a rotation and a kinking of the PA. The consequent distortion of the suture line may cause re-opening of bleeding sites that are not visible when the artery is stretched downward by the atelectatic lower lobe.Conduit interposition may be necessary, after a sleeve resection of the PA, when an excessive distance between the two vascular stumps ensues. This condition would produce a high tension on an end-to-end anastomosis. Such a technical situation may occur more frequently on the left side, when a left upper lobe tumor infiltrates the PA extensively but the lobar bronchus is not involved. This infrequent situation  may determine a long bronchial segment separating the two widely spaced PA stumps; thus, an end-to-end anastomosis can be not feasible. A tubular prosthesis generally of biological material, such as autologous or heterologous pericardial tissue ,28,29 orA very interesting alternative for conduit reconstruction is the autologous pulmonary vein conduit when available , because this is an ideal substitute for the PA: it has adequate thickness and structural similarity with the arterial wall. Moreover, the elasticity of the two tissues is comparable.A better proximal control of the superior pulmonary vein can be obtained by opening the pericardium when performing an upper lobectomy. Then, the superior vein is fully dissected, sutured proximally  with a vascular mechanical stapler and ligated distally at the level of its extralobar branches, thus dividing it and creating an autologous vein conduit of approximately 1.5 to 2.5 cm, which is preserved in saline solution for few minutes . Before It is common to think that an extended surgical incision is preferable to perform complex bronchovascular reconstructions. Nevertheless, a minimally invasive approach including video-assisted thoracic surgery (VATS) is widely described for SL ,37. Due Another aspect that still remains controversial is the use of postoperative steroids in patients undergoing bronchial reconstruction. The postoperative use of low-dose steroids after an SL with bronchial and vascular reconstruction has proven favorable in the authors’ experience because it may help to prevent anastomotic edema and secretion retention, thus reducing the risk of atelectasis and granuloma formation. Aerosolized steroids (methyl-prednisolone 5 mg twice a day) are also part of postoperative treatment. The short-term outcome of patients undergoing isolated PA reconstruction is generally not influenced by the use of steroids.Bronchoarterial fistula is one of the most dangerous complications after lung reconstructive surgery, and a viable tissue flap, interposed between the bronchus and the PA, can effectively prevent the fistula occurrence. Researchers have described ,39 the uAt the opening of the chest, the intercostal muscle flap is prepared, avoiding inserting the rib retractor until the flap is not entirely obtained in order to not crush the intercostal vessels and interrupt the vascularization. After the incision of the periosteum of the fifth rib, it is separated from the bone together with the underlying intercostal muscle. Attention has to be paid to preserve the muscular insertion to the periosteum and to avoid injuring the intercostal neurovascular bundle. The intercostal muscle is then incised at the level of the superior margin of the sixth rib, and the flap is divided at the anterior insertion, ligating the pedicle. After completing the bronchial and the vascular anastomoses, a right-angle clamp is inserted between the PA and the bronchus, and the edge of the flap is slid backward to encircle the bronchial anastomosis, thus separating the bronchus from the PA. The pleural side of the flap should be in contact with the bronchial anastomosis and then fixed to the bronchus by interrupted absorbable 4-0 sutures.Avoiding tension on the anastomosis is one of the most important principles in bronchial and vascular reconstructive procedures.If the anastomosis shows any grade of tension, it is advisable to complete the posterior portion of the suture and subsequently to parachute the arterial stumps together while lifting the lower lobe. In case of bronchovascular resection with patch reconstruction and bronchoplasty (end-to-end anastomosis), the axis of the bronchus is shortened, while the length of the PA remains unaltered. The PA may tend to kink and fold over on itself. This risk is increased by the repositioning of the PA due to the re-expansion of the lower lobe. Thrombosis may occur in this setting because of the impairment of blood flow. Cutting away the redundant segment and performing an end-to-end anastomosis could solve the problem in these circumstances.A tension-free suture can be obtained by dividing the pulmonary ligament or, more frequently on the right side, opening the pericardium around the pulmonary vein during an end-to-end anastomosis reconstruction.According to the authors’ experience, the choice of the prosthetic tissue used for vascular reconstruction is a crucial factor. Autologous options may offer a number of advantages. If considering conduit reconstruction, the pulmonary vein is one of the best choices because it offers a “ready-to-use” conduit with tissue characteristics similar to those of the PA. The autologous vein conduit is fresh and unpreserved, cost-free, and biocompatible, but it has a limited length. Conversely, bovine pericardial tissue is less cost-effective and less biocompatible, but it has no limit in the amount of tissue. Adequate sizing of the conduit length represents a key point to the final success of the procedure.n = 92), bovine pericardium (n = 44), autologous pericardium (n = 41), and porcine intestinal submucosal patch (n = 37). Median age and weight at the time of surgery were 12.1 months and 8.5 kg. Reintervention occurred at 34 sites (15.9%). According to a Cox proportional hazards regression, preoperative renal failure  and weight at surgery  were associated with reintervention, while the patch material did not influence the reintervention rate (p = 0.197). Cost per unit patch ranged from $0 for untreated autologous pericardium to $6105 for homograft patch. No relationship between the patch material used and reintervention rate was found. This finding combined with the widely different costs of patches may help surgeons in the choice of tissue to use for the patch.If considering patch reconstruction, a recent analysis by Ebert et al.  has evalTo assess the patency of the reconstructed PA in the postoperative period, magnetic resonance angiography (MRA) or computed tomography (CT) scan with contrast medium and three-dimensional (3D) volume rendering may provide effective imaging of the PA. The noninvasive perfusion lung imaging is unnecessary if the patient is asymptomatic. During the oncological follow-up period, a CT scan with contrast medium is the proper diagnostic tool to evaluate the patency of the PA and its distal branching as well as the eventual relapse of the disease.Proper anticoagulation management is a fundamental aspect when PA reconstruction is required and has not been adequately clarified by the initial reports . In the During surgery, sometimes, a leakage from the suture line may be unseen, since the PA is a low-pressure vessel. Therefore, a postoperative bleeding may appear on the first or second postoperative day after a patch or anastomotic reconstruction. A blood loss of as much as 800 to 1000 mL daily may occur after 1 or 2 days of no drainage, which may last for 1 or 2 days and then stop spontaneously, independently from anticoagulation. After unclamping and vessel distension, sutures too wide apart may result. An eventual bleeding would not appear immediately because the PA is stretched downward by the atelectatic lower lobe, and modest juxtaposition of the tissue edges is enough to counteract the low PA pressure. Nevertheless, postoperatively when the re-expansion of the lower lobe uplifts the hilum, the suture line may be distorted by the rotation and kinking of the PA, reopening the bleeding site. Therefore, checking the suture line carefully and assessing the PA position after re-expansion of the residual lobe is mandatory, particularly when using autologous pericardial patches.SL can be performed safely and successfully after neoadjuvant therapy, without an increased complication rate ,44,45,46Primarily, a meticulous surgical technique is the main factor allowing a good final outcome in every reconstructive procedure of the PA. The induction therapy  may theoretically increase the risk for postoperative complications because the vascularization and trophism of the tissues may be affected.A fistula may be the result of technical anastomotic complications after bronchial or vascular reconstruction.Tissue damage and fibrotic alteration induced by the neoadjuvant therapy may cause compromised healing and then anastomotic dehiscence. If considering operations with associated PA reconstruction, the most dangerous potentially life-threatening complication is represented by the broncho-arterial fistula.The authors, based on their long-term experience, consider the protection of the bronchial anastomosis by viable tissue an effective procedure to minimize the risk of anastomotic dehiscence. The use of a vital vascularized flap may allow preventing the occurrence of bronchoarterial fistula, a rare but life-threatening event, especially in patients undergoing combined bronchial and PA reconstruction. The risk of PA erosion and consequent fatal bleeding may be minimized by the intercostal muscle flap interposition between the bronchus and the PA. Induction therapy seems not to significantly impair the intercostal muscle, representing the most adequate tissue for wrapping the reconstructed bronchus. Although a progressive heterotopic calcification of the muscular flap possibly causing a severe bronchial stenosis has been described in some papers, the present authors have not reported such a complication in their experience .Alternative protective tissues have been reported to reduce the risk of dehiscence, such as mediastinal fat pad, pericardial or pleural flap, omentum, or internal mammary artery pedicles ,38,39.The complication risk in isolated PA reconstructive procedures seems not to be affected by induction therapy. In particular, bleeding and thrombosis  are considered not to be significantly influenced by the induction treatment. As previously described, bleeding can occur later, after lung re-expansion, which may induce a change in the PA axis. Chemotherapy and radiotherapy may induce a reduction in the lung parenchyma elasticity. Therefore, the re-expansion of the residual lobe after induction treatment may require longer time compared to standard cases. In these cases, late unforeseen blood loss with spontaneous resolution within 24 to 48 h may be observed.n = 1), arrhythmia (n = 1), empyema (n = 2), PA thrombosis (n = 1), and late bronchial stenosis in two patients who underwent double sleeve lobectomy. In the report by Shrager [p = 0.5953). The 90-day postoperative mortality rate was 8.2% (12/147) overall, 5.9% (7/118) in the bronchoplasty group, and 17.2% (5/29) in the broncho-angioplasty group (p = 0.047). Cerfolio published in 2007 a report including 42 PA reconstructions [n = 6/14.3%). Alifano in 2009 [n = 5). Three deaths occurred after right lobectomy (two with bronchoplasty), and two occurred after left lobectomy. Postoperative pneumonia and acute respiratory distress (with no infection identified) were responsible for three deaths. In two further patients, acute myocardial infarction followed by intractable cardiogenic shock was the cause of death.The postoperative complications rate in early experience by the present authors  was 13.4 Shrager  et al.,  Shrager  reported Shrager , there wructions . Transie in 2009  reportedp = 0.043), cardiovascular disease (p = 0.007), previous neoplasm (p = 0.030), p stage (p = 0.002), smoking (p = 0.020), and FEV1 (p = 0.035). Multivariate analysis showed that only cardiovascular disease (p = 0.022) and FEV1 (p = 0.039) were independent predictors of postoperative mortality. No statistical difference was found with respect to associated bronchoplasty or the extent of resection (lobectomy or bilobectomy).Other complications (not responsible for death) occurred in 27 (29.0%) other patients and were in some instances associated: postoperative pneumonia (n = 12), supraventricular arrhythmias (n = 5), persistent air leak without evident bronchopleural fistula (n = 5), respiratory failure (n = 5), atelectasia without pneumonia (n = 3), acute pericarditis (n = 1), and delirium (n = 1). One of the largest studies focusing on the present authors’ PA reconstruction experience was published by Venuta et in 2009 [Among the analyzed factors, the following were associated with postoperative death at univariate analysis: age  as well as with a higher incidence of major complications (p = 0.004). Long-term results showed comparable outcomes for PN vs. SL if considering 5-year disease-free survival  and overall 5-year survival .When PA reconstruction is compared to PN, irrespective of neoadjuvant therapy, SL is constantly reported as a valid alternative, with lower short-term mortality and morbidity, without affecting long-term oncologic results. Schiavon et al.  publishep = 0.047).Recently, Hattori  et al. hp = 0.381) and recurrence-free survival (p = 0.619) between the two surgical procedures , thus confirming that this complex procedure is safe and reliable for centrally located non-small cell lung cancer concurrently involving the PA and bronchus.In another recent study from Yang et al. , analyziOne of the strongest indicators influencing the decision to perform an SL rather than a PN is the postoperative quality of life. Even though SL after induction therapy has not been adequately analyzed in this setting, a number of studies indicate that lung parenchyma sparing is related with better postoperative quality of life, determining a superior cardiopulmonary reserve, less pulmonary edema, and decreased right ventricular dysfunction caused by a lower pulmonary vascular resistance ,18. FergPA reconstruction associated with lobectomy is a safe and viable parenchymal sparing intervention to radically treat lung cancer, allowing better long-term survival, lower perioperative morbidity and mortality rates and functional benefits if compared with PN.


Heart failure (HF) patients are in a hypercoagulable state that predisposes them to an intracardiac thrombus. We aim to assess the clinical features of patients with HF and intracardiac thrombus.Patients diagnosed with HF with intracardiac thrombus were enrolled in this study. Patients' demographics, clinical comorbidities, laboratory tests, and cardiac imaging parameters are recorded. Baseline characteristics are described; the relationship between intracardiac thrombus location and cardiac underlying diseases, New York Heart Association (NYHA) class, and left ventricular ejection fraction (LVEF) are analyzed; and the anticoagulation rate is summarized.A total of 1,248 patients were included in the study. Most patients were men (72.2%) with a mean age of 54 years. The left ventricle is the most frequently involved (66.8%), and the prevalence of left ventricular thrombus is more in patients complicated with coronary artery diseases, ventricular noncompaction cardiomyopathy, and dilated cardiomyopathy . When combined with atrial fibrillation, atrial flutter, hypertrophic cardiomyopathy, restrictive cardiomyopathy, or valvular cardiomyopathy, the intracardiac thrombus is mostly likely to occur in the left atrium. The incidence rate of left cardiac thrombosis increased with the decline of LVEF, an increase of NYHA class, and enlargement of a cardiac chamber. Overall, the anticoagulation rate was 56.8%, with warfarin still the mainstay drug (45.1%), while the prescription of non-vitamin K antagonist oral anticoagulants rose year by year. As for imaging modalities for thrombus detection and diagnosis, transthoracic echocardiography was the most widely performed (75.1%).This study summarizes the underlying disease constitution, thrombus location and related factors, imaging modalities, and antithrombotic profile in HF patients with intracardiac thrombus comprehensively. Intracardiac thrombi are frequently reported in patients with underlying cardiovascular diseases and are commonly discovered at autopsy. In an analysis of 11,724 autopsy cases carried out by Pradeep Vaideeswar et al., 276 (2.4%) had intracardiac thrombus , with inBy assessing the clinical characteristics and thrombus features of HF patients admitted to our center, this study aims to give insights into the clinical characteristics of patients with HF and intracardiac thrombus.This is a single-center retrospective cohort study. We consecutively enrolled patients hospitalized in the internal medical department of Fuwai Hospital, CAMS & PUMC, from October 2008 to May 2018 who were meticulously examined with inclusion and exclusion criteria. Demographics, clinical characteristics, laboratory profiles, recorded comorbidities, use of antithrombotic agents, and imaging parameters, such as intracardiac thrombus location, cardiac structure, and cardiac function, were retrospectively collected. Intracardiac thrombus location was described in the imaging reports. Cardiac structure and function were assessed by transthoracic echocardiography (TTE).Inclusion criteria are as follows: (1) diagnosed as HF according to the Chinese Guideline for the Diagnosis and Treatment of Heart Failure 2018 , and (2)Exclusion criteria are the following: (1) age under 14 years, and (2) baseline data incomplete.Baseline data, including age, sex, body mass index (BMI), systolic blood pressure (SBP) at admission, diastolic blood pressure (DBP) at admission, heart rate (HR) at admission, underlying cardiovascular diseases, major comorbidities, New York Heart Association (NYHA) functional class, results of blood routine, liver function, kidney function, and other blood tests, were collected along with thrombus-related indexes, such as size and location reported on echocardiography/CMR/CT, cardiac chamber diameter, and left ventricular ejection fraction (LVEF) reported on echocardiography.t-test. Categorical variables were compared by the Chi-square test. A trend test was applied among the groups.Continuous variables were shown as mean values and standard deviations, or medians and interquartile ranges as appropriate. Categorical variables were presented as frequency and percentage. Continuous variables were compared between the groups with Student's P < 0.05 were considered to be statistically significant.All statistical tests were two-tailed, and The analysis was performed with the use of SAS software, version 9.4 , and R 4.0.3  statistical software.Baseline characteristics are detailed in Overall, the prevalence of left-sided intracardiac thrombi is more than right-sided ones, and the ventricular ones constitute the majority. The left ventricle is the most frequently involved among the four chambers (66.8%), followed by the left atrium (32%) .The characteristics of HF patients grouped by location are presented in P-value for trend all < 0.0001). However, no such trend is observed in the right ventricular thrombosis, possibly due to the extremely low incidence rate . Analogously, the incidence rate of left ventricular thrombosis increased with the decline of LVEF, whereas the opposite pattern is true for the left atrial thrombus  .The proportion of patients with poor cardiac function  is found to be high in our study population, as is shown in  0.0001) . A similP < 0.0001)  is associated with left atrial thrombosis, and left ventricular end-diastolic diameter (LVEDD) is associated with left ventricular thrombosis. Cardiac diameter is significantly higher in patients with intracardiac thrombus ( 0.0001) .In our study, the overall anticoagulation rate was 56.8%, among which warfarin was the main treatment (45.1%). Antiplatelets were prescribed in 49.7% of the patients . The admP < 0.01) and were inclined to concomitant antiplatelet use . There was no significant difference in liver function and renal function between patients on and off oral anticoagulation , followed by CT , while other imaging modalities accounted for only a small proportion , and non-ischemic heart disease accounted for 36.2%, consistent with the overall etiology constitution in China. Compared to the China Heart Failure Registry Study, in which patients with CAD accounted for 49.4% of the hospitalized patients with HF and non-ischemic heart disease accounted for 23.1%  , in line with the previous literature.Increased LVEDD (>60 mm) and low LVEF are independent predictors of intracardiac thrombosis in cardiomyopathy patients . In the Left atrial thrombus is the major type of intracardiac thrombus in HCM and RCM patients. HCM is characterized by left ventricular diastolic dysfunction and wall thickness, attributable to the development of AF. This link is manifested by a high prevalence of AF in HCM, ranging from 17 to 28% . Left atIn a study carried out by Mccarthy et al., HF was the most common precipitating factor of intracardiac thrombosis (68.5%), and 86% of the patients were complicated with reduced EF (LVEF ≤ 40%) . SimilarP = 0.005)  . It is sThe present study shows that TTE is the most important method in thrombus detection in HF patients, which is also the most commonly used method for the evaluation of cardiac structure and function. Compared to TEE, CT, and CMR, TTE is economically friendly, radiation-free, non-invasive, and widely accepted as the primary screening test for thrombus detection. TEE is more accurate and is the first choice in left atrial appendage thrombus detection. However, for operators, TEE requires higher operating skills; for some patients, it increases the pain to a certain extent. The above-mentioned factors may limit the wide application of TEE in the clinical setting. CT is the second most commonly applied method for the detection of intracardiac thrombus. Our study shows that CT markedly improved left atrial thrombus assessment, especially left atrial appendage thrombus. This is supported by a previous study, in which CT showed outstanding performance with high sensitivity, specificity, positive predictive value, and negative predictive value in identifying left atrial appendage contrast filling defect  compared to the gold standard (TEE and intracardiac echocardiography [ICE]) .The overall anticoagulation prescription rate was 56.8% in our study, 45.1% were on warfarin therapy, and nearly half of the patients were off anticoagulation. Despite a relatively low prescription rate, an increasing trend in the anticoagulation rate is encouraging . WarfariAs far as we know, this is the first study to focus on the clinical features of HF patients with intracardiac thrombus. It summarizes the underlying disease constitution, thrombus location, and status quo of anticoagulation in this population comprehensively; provides forceful evidence-based medical proof to better understand the clinical features of HF patients with intracardiac thrombus in China, and lays a foundation for continued intervention studies. In addition, it provides clinicians with significant clues to observe and intervene in this population.This study has some limitations. It is a single-center observational study. Data were collected in a relatively high-level hospital, so the results are less representative of the whole population in China. Furthermore, its retrospective nature refrains us from obtaining all the details. It is of great necessity to carry out a registry study and thrombi-prevention study in this population to further determine whether patients will benefit from preventive anticoagulation therapy, especially in those with HF and sinus rhythm.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 Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.Conception and design of the study: MZ, LH, YZ, and JZ. Analysis and interpretation of data and drafting the article: MZ and LH. Acquisition of data: MZ, LH, LL, PT, LZ, XZ, BH, JF, YH, and QZ. Revising the manuscript critically for important intellectual content: YZ and JZ. All authors contributed to the article and approved the submitted version.This work was supported by the Key Projects in the National Science and Technology Pillar Program of the 13th Five-Year Plan Period (Grant Number 2017YFC1308300 to JZ), Beijing, People's Republic of China.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.


Because the presence of immunocompetent cells in the myocardium is associated with the pathological stage and/or myocardial viability, we explored relationships between functional recovery after left ventricular assist device implantation and the distribution of immunocompetent cells in non-ischaemic dilated cardiomyopathy patients.We reviewed 50 consecutive dilated cardiomyopathy patients implanted with HeartMate II at our institute between April 2013 and December 2018 who were treated with optimal medical therapy during left ventricular assist device support. Patients were stratified by improvement of the left ventricular ejection fraction at 6 months after implantation: ≥ 10% increase (Gr ≥ 10%), 5–10% (Gr 5–10%), and ≤ 5% (Gr ≤ 5%). T cells and macrophages were evaluated in the apical myocardium after left ventricular assist device implantation.During left ventricular assist device support, 12 patients underwent heart transplantation and 2 patients died. Four patients with Gr ≤ 5% were readmitted because of congestive heart failure, but none with Gr ≥ 10%. Macrophages and T cells in the left ventricular myocardium with Gr ≥ 10% were significantly more present compared to those in other groups.The distribution of immunocompetent cells in the left ventricular myocardium might predict myocardial viability of this pathology after implantation. Non-ischaemic dilated cardiomyopathy (NIDCM) is the most prominent pathology influenced clinically by the degree of functional recovery under durable left ventricular assist device (LVAD) support. NIDCM is generally a progressive pathology that potentially leads to abolition of left ventricular (LV) functions, which induces aortic insufficiency . The majLVAD implantation reverses LV remodelling by unloading the LV . Reducti®  implantation for advanced NIDCM at the National Cerebral and Cardiovascular Center between April 2013 and December 2018. Data were collected from medical charts, operation reports, and referral letters in December 2018.The institutional surgical database contained a consecutive series of 50 patients who underwent HeartMate IISurgical indication of LVAD implantation was discussed by the institutional multidisciplinary heart team, which comprised cardiologists, surgeons, transplant physicians, transplant coordinators, and co-medical staff, who particularly focussed on medical and social indications of heart transplantation because an LVAD was implanted for “bridge-to-transplantation” purposes. Selection of the LVAD device was subsequently determined by (1) anatomies of the heart and adjacent organs/tissues, (2) the structure and functions of the heart, and 3) proficiency in device handling of the patient and family.Implantation of the LVAD was performed via the median sternotomy approach. Additional tricuspid annuloplasty using a prosthetic ring or aortic valve plasty by a coaptation stitch  was perfPost-operatively, all cases were treated at the intensive care unit until sufficient recovery for transfer to the general ward. Anti-coagulant therapy by continuous heparin infusion was started within 24 h post-operatively, while the heparin dose was titrated to maintain an activated partial thromboplastin time of 50–70 s. Subsequently, 100 mg aspirin per day and warfarin were administered to target INR 2.5–3.5 when oral intake was restarted. After stabilising patient haemodynamics, aggressive medical treatments by β-blockers, angiotensin-converting enzyme inhibitors, and/or spironolactone were started, which depended on blood pressure, heart rate, and renal functions. After discharge from the hospital, all cases regularly visited the institutional outpatient clinic for review.All patients were examined by standard transthoracic echocardiography within 7 days prior to LVAD implantation and at 6 months after LVAD implantation. Standard data, such as LV end-diastolic dimension (LVDD), end-systolic dimension (LVSD), and LV ejection fraction (LVEF) of the LV, were obtained from the official echocardiographic report. LV mass indexed to the body surface area was estimated by the LV cavity dimension and wall thickness at the end-diastolic phase. Valve regurgitation was classified as grade 0 (none), 1 (trace), 2 (mild), 3 (moderate), or 4 (severe). The serum brain natriuretic peptide (BNP) level was measured at 1, 6, and 12 months after LVAD implantation. The patients were stratified by improvement of LVEF at 6 months post-LVAD implantation: ≥ 10% increase (Gr ≥ 10%), 5–10% (Gr 5–10%), and ≤ 5% (Gr ≤ 5%).Sampled LV apex tissue at the time of LVAD implantation surgery was fixed in formalin and embedded in paraffin. Five-micrometre-thick sections were stained with haematoxylin/eosin or Masson’s trichrome to analyse the cardiomyocyte size or collagen area, respectively. Additionally, the sections were immunolabelled with mouse monoclonal antibodies against CD3  or CD68  to label T cells or macrophages, respectively. The immunolabelled sections were visualized by a Bond Polymer Refine Detection Kit .Whole section images were scanned with an Aperio Scan-Scope XT (Leica Biosystems) and digital sections were viewed using Aperio ImageScope software (Leica Biosystems). Photomicrographs were recorded in five randomly selected high power fields and a low magnification whole view of the digitised image. The size of cardiomyocytes was evaluated in sections stained with haematoxylin/eosin by measurement of ≥ 30 cardiomyocytes in high power fields. The collagen area fraction in the whole myocardial area was determined automatically by Aperio ImageScope software. The numbers of infiltrating CD3- and CD68-positive cells in photomicrographs were counted in a blinded manner.® 13 . All quantitative data are expressed as the mean ± standard deviation (SD). The statistical significance of differences was analysed using the unpaired Student’s t test for parametric continuous variables and the Mann–Whitney U test for non-parametric continuous variables. Event-free survival curves were constructed using the Kaplan–Meier method.Statistical analysis was performed using JMPThe backgrounds and characteristics of the patients, which included 50 cases with NIDCM, are presented in Table Echocardiographically, all patients showed substantial dilatation of the LV and poor LVEF without regional wall motion abnormalities. Moderate tricuspid regurgitation was noted in one patient, whereas no cases showed moderate or more aortic regurgitation. Right heart catheter analysis showed that 26 and 11 patients were categorized as Forrester Type 4 and Type 3, respectively. The RV function was estimated by a right atrial pressure/pulmonary capillary wedge pressure ratio of > 0.5, so that 11 patients were categorized as right ventricular (RV) failure. Thirteen patients (26%) showed serum BNP of > 800 pg/ml. All patients were histologically diagnosed as NIDCM by a biopsy specimen of the RV and/or a resection specimen of the LV apex prior to LVAD implantation.LVAD was implanted via the median sternotomy approach. Tricuspid annuloplasty was performed in 11 patients 22%) who had mild or more tricuspid regurgitation. Aortic valve plasty by a coaptation stitch  was cond2% who haThere was one in-hospital mortality because of cerebral infarction (2%). One patient was categorized as RV failure by prolonged inotrope support post-operatively. No patient was tracheotomised. Intensive care unit stay was an average of 5 days. All surviving patients were discharged without permanent disorders such as neurological deficit or maintenance haemodialysis.After discharge, there was one mortality until the latest follow-up because of cerebral infarction at 38 months post-LVAD implantation. Four patients (8%) presented with congestive cardiac failure that was treated in-hospital. Among them, two patients had received multiple in-hospital treatments for congestive cardiac failure. Congestive cardiac failure was caused by aortic valve regurgitation and/or RV failure. Other complications after discharge included driveline infection in 13 patients, gastrointestinal bleeding in 4, and cerebral infarction in 5. Kaplan–Meier analysis revealed that 1- and 5-year survival rates were 98 and 92%, respectively and that 1- and 5-year avoidance rates of congestive cardiac failure treated in-hospital were 96 and 89%, respectively.All in-hospital surviving patients (n = 49) were examined by standard transthoracic echocardiography within 7 days prior to LVAD implantation and at an average of 6.0 months (5.0–6.3 months) post-LVAD implantation. As a result, the LVEF was constant post-LVAD implantation, while LVDD and LVSD were decreased significantly post-LVAD implantation Fig. . Conversn = 4, Gr 5–10%; n = 6, and Gr ≤ 5%: n = 39. LVDD and LVSD in patients with Gr ≥ 10% were reduced significantly post-LVAD implantation, whereas those in patients with Gr ≤ 5% were not significantly different between pre- and post-LVAD implantation. The reduction rate in serum BNP post-LVAD implantation in patients with Gr ≥ 10% was significantly greater than that in other groups.The patients were stratified by improvement of LVEF at 6 months post-LVAD implantation: Gr ≥ 10%; By comparing clinical characteristics in each group, the durations of heart failure were 88 ± 89 months, 79 ± 66 months, and 48 ± 61 months in patients with Gr ≤ 5%, Gr 5–10%, and Gr ≥ 10%, respectively. The numbers of patients with an implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) were 19 (49%), 0 (0%), and 2 (50%) in patients with Gr ≤ 5%, Gr 5–10%, and Gr ≥ 10%, respectively. The numbers of patients with moderate or severe mitral regurgitation were 22 (52%), 3 (6%), and 2 (50%) in patients with Gr ≤ 5%, Gr 5–10%, and Gr ≥ 10%, respectively. The QRS intervals were 121 ± 25 ms, 101 ± 14 ms, and 140 ± 45 ms in patients with Gr ≤ 5%, Gr 5–10%, and Gr ≥ 10%, respectively. The β-blocker doses were 12 ± 7 mg, 12 ± 7 mg, and 10 ± 2 mg in patients with Gr ≤ 5%, Gr 5–10%, and Gr ≥ 10%, respectively.2) was significantly greater than that of patients with Gr 5%–10% and Gr ≤ 5%   was significantly greater than that of patients with Gr 5–10% and Gr ≤ 5%   or CD3-positive T cells (p = 0.086) and myocyte size. Similarly, there was no significant correlation between the number of CD68-positive macrophages (p = 0.063) or CD3-positive T cells (p = 0.18) and the collagen area.Relationships between the change in LVEF and the myocyte size or collagen area were analysed statistically. There was a significant negative correlation between the increase of LVEF and the myocyte size Fig. a. ConverOut of 50 patients, 4 with NIDCM-induced advanced cardiac failure showed substantial cardiac functional recovery after LVAD implantation. LVEF recovery was associated with reductions in the LV size and serum BNP. Additionally, greater numbers of CD68-positive macrophages and CD3-positive T cells were present in patients with functional recovery, which indicated that the viability of cardiac tissue may be, at least in part, determined by immunocompetent cells and myocardial inflammation. There were no significant differences in accumulation of immunocompetent cells between Gr 5–10% and Gr ≤ 5%. In contrast, cut-off value of LVEF recovery at 6-monthes post-LVAD implantation reportedly 5% in some publications . In addi2+ transport, reductions in cytokines, improvements in heart failure-related gene expression, upregulation of β-adrenergic receptors, and reductions in β1-adrenoceptor autoantibodies [Nakayama et al. reported that the presence of macrophages and T cells was associated with poor outcomes of NIDCM patients . These rtibodies , 17. ThePreoperative ICD, CRT-D, or a β-blocker might affect the remodelling process of the LV after LVAD implantation. However, there were no statistically significant relationships between the number of patients with ICD/CRT-D or the β-blocker dose and the degree of functional recovery in this study. This may be explained by the fact that all cases were treated by optimized device/medical therapies prior to the LVAD implantation. Furthermore, there are reportedly multiple predictive factors of reverse remodelling in NIDCM, such as the duration of heart failure, the degree of mitral regurgitation (MR), and QRS interval. There was a significant correlation between the degree of functional recovery and the duration of heart failure. Conversely, MR or the QRS interval at the time of LVAD implantation did not show a significant correlation with the degree of functional recovery. NIDCM is a progressive disease represented by gradual development of myocardial tissue damage. The duration of heart failure is therefore an important factor to assess myocardial viability. LV unloading by LVAD implantation would activate the reverse remodelling process more effectively in more viable myocardium. Conversely, MR and a wide QRS would reflect heterogenous or end-stage myocardial damage, either of which would be less affected by LV unloading.The results of the present study have important implications in contemporary clinical practice for patients with stage D heart failure as follows. First, the presence of immunocompetent cells in the LV apex at the time of LVAD implantation surgery predicted long-term outcomes under LVAD support. Intensive medical treatments or early surgical intervention, which include transplantation of a marginal donor heart, might improve outcomes of patients with poorly distributed immunocompetent cells. Second, patients who have abundant immunocompetent cells might be good candidates for LVAD weaning. Additional treatments, such as cardiac regeneration therapy, might be indicated for bridge-to-recovery in this patient population.This study is limited by the small number of enrolled patients with only four cases showing substantial functional recovery post-LVAD implantation. Despite the relatively consistent results in this study, a larger number of enrolled patients would confirm the findings of this study and contribute to more detailed data, particularly histological results. Additionally, the roles of CD3-positive T cells and/or CD68-positive macrophages were uncertain in this study. Therefore, more specific immunohistological assessments and experimental animal studies are warranted.In conclusion, despite aggressive medical treatments post-LVAD implantation, functional recovery was not frequently seen in advanced NIDCM patients. Immunocompetent cells in the LV myocardium might be important to predict myocardial viability of this pathology.