New oblique impact methods for evaluating head injury mitigation effects of helmets are emerging, which mandate measuring both translational and rotational kinematics of the headform. These methods need headforms with biofidelic mass, moments of inertia (MoIs), and coefficient of friction (CoF). To fulfill this need, working group 11 of the European standardization head protection committee (CEN/TC158) has been working on the development of a new headform with realistic MoIs and CoF, based on recent biomechanics research on the human head. In this study, we used a version of this headform (Cellbond) to test a motorcycle helmet under the oblique impact at 8 m/s at five different locations. We also used the Hybrid III headform, which is commonly used in the helmet oblique impact. We tested whether there is a difference between the predictions of the headforms in terms of injury metrics based on head kinematics, including peak translational and rotational acceleration, peak rotational velocity, and BrIC (brain injury criterion). We also used the Imperial College finite element model of the human head to predict the strain and strain rate across the brain and tested whether there is a difference between the headforms in terms of the predicted strain and strain rate. We found that the Cellbond headform produced similar or higher peak translational accelerations depending on the impact location (−3.2% in the front-side impact to 24.3% in the rear impact). The Cellbond headform, however, produced significantly lower peak rotational acceleration (−41.8% in a rear impact to −62.7% in a side impact), peak rotational velocity (−29.5% in a side impact to −47.6% in a rear impact), and BrIC (−29% in a rear-side impact to −45.3% in a rear impact). The 90th percentile values of the maximum brain strain and strain rate were also significantly lower using this headform. Our results suggest that MoIs and CoF have significant effects on headform rotational kinematics, and consequently brain deformation, during the helmeted oblique impact. Future helmet standards and rating methods should use headforms with realistic MoIs and CoF  to ensure more accurate representation of the head in laboratory impact tests. Pedal cyclists and motorcyclists are among the most vulnerable road users. In 2019, 846 pedal cyclists and 5,014 motorcyclists died, and nearly 49,000 pedal cyclists and 84,000 motorcyclists were injured in road traffic collisions in the United States . In GreaHeadforms are used in laboratory test methods to evaluate the performance of helmets. The fidelity of physical properties of headforms is crucial to ensure that laboratory tests adequately predict mechanical measures of injury that are expected in real-world collisions under the same impact conditions. Current helmet standards use translational acceleration of the headform to assess the performance of helmets . HoweverThe key properties that affect translational and rotational motion of the headform are mass, moments of inertia (MoIs), and coefficient of friction (CoF). However, the EN960 and Hybrid III (HIII) headforms, which are widely used in helmet standards, rating methods, and helmet research , have liThe CoF between the headform and helmet liner also plays a key role in determining the head kinematics during the impact. The CoFs between the helmet liner and the EN960 and HIII headforms were measured as 0.16 and 0.75, respectively . The HIIDespite these attempts on investigating the effects of MoIs or CoF on head rotational kinematics, a key limitation of these studies is that none of them used headforms that have both realistic MoIs and CoF as in the human head. For instance, To address the need for a headform that has both realistic MoIs and CoF, working group 11 (WG11) of the European standardization head protection committee (CEN/TC158) has developed specifications for a new headform based on recent biomechanics research on the mass, center of gravity, moments of inertia, and coefficient of friction of the scalp/helmet interface and the shape of the head. A version of the headform, with both realistic MoIs and CoF, has been prototyped by Cellbond Ltd. This study aims to introduce an early version of this headform, called the Cellbond headform hereafter, and compare its measurements in the helmeted oblique impact with those from the HIII headform, which is widely used for testing helmets under the oblique impact in research studies and rating methods . It shouWe used two headforms to conduct the helmet tests . We usedxx, 2.2% difference in Iyy, and 2.6% difference in Izz. For the HIII headform, the differences are 30.9% (Ixx), 1.2% (Iyy), and 39.2% (Izz).A recent study has determined the relationship between the head mass and MoIs using both cadaveric data and living human computed tomography (CT) scans . It has We conducted friction tests to measure the CoF of the two headforms . A polyeectively .A recent study on the sliding behavior of the scalp using postmortem human heads has shown that the scalp sliding mainly includes an initial skull–scalp sliding followed by scalp–liner sliding . They haThe oblique impact tests were conducted at the Human Experience, Analysis, and Design (HEAD) lab at Imperial College London. We generally followed the newly introduced oblique impact test method in the ECE22.06 motorcycle helmet test standard, including the helmet fitting, impact velocity, and oblique anvil. . The onlWe used the Bell Qualifier helmet (size M and a fitting head circumference of 57 cm–58 cm), purchased from the United Kingdom market. The helmet was fitted onto the headforms based on the helmet fitting requirements of ECE22.06 . A load The helmeted headforms were tested at five impact locations . The angThe helmeted headform was dropped onto a 45° anvil at a velocity of 8.0 m/s (+0.15/− 0.0) . The anvThe translational and rotational accelerations of the headform  were meaTo evaluate the brain deformation from the tests, we used the Imperial College finite element (FE) model of the human head  Figure . This moFor each element of the brain tissue, we determined the maximum value of the first principal Green–Lagrange strain and strain rate during the simulation . We further determined the 90th percentile strain and strain rate of the entire brain, which were used to evaluate the overall brain response to the impact.We used four kinematics-based injury metrics and two tissue-based injury metrics to evaluate brain injury. The kinematics-based injury metrics were peak translational acceleration (PTA), peak rotational acceleration (PRA), peak rotational velocity (PRV), and brain injury criterion (BrIC) . PTA hasFor each injury metric, we performed two-way ANOVA (significance level: 0.05) to determine the effects of the headform and impact location, as well as their interaction. Then, for each injury metric at each impact location, we evaluated the difference between the two headforms by conducting pairwise comparisons (post hoc).Similar observations were made for the strain rate distribution . For thep < 0.001). In addition, the two factors have interactions for all the injury metrics, except the brain strain.We conducted a two-way ANOVA, using headform and impact location as the factors. The results showed that both the headform and impact location have significant effects on all the injury metrics .For the rotational kinematics-based injury metrics, the Cellbond headform produced significantly lower values than the HIII headform in all impact locations. PRA with the Cellbond headform was 41.8%–62.7% lower than that with the HIII headform. This difference was slightly lower for PRV (29.5%–47.6%) and BrIC (29%–45.3%).The Cellbond headform also led to significantly lower brain strain and strain rate than the HIII headform. For the 90th percentile strain, the Cellbond headform had 41.5%–60.3% lower values than the HIII headform. For the 90th percentile strain rate, the difference was much higher (56.8%–76.1%).For PRA, brain strain, and strain rate, the largest difference between the two headforms was observed in impact 3 (side). For PTA, PRV, and BrIC, the largest difference was observed in impact 2 (rear). These results confirm that the headform has an interaction with the impact location in determining the value of the injury metrics.In this study, we used the HIII headform and Cellbond headform developed based on the CEN/TC158/WG11 work to perform the oblique impact on a motorcycle helmet. The HIII headform is often used to test helmets under oblique impact conditions, where translational and rotational kinematics of the headform is measured and used to assess the performance of helmets . In contWe followed the impact conditions of the oblique impact test method in the newly issued ECE22.06 motorcycle helmet test standard . The fivWe used both kinematics-based and tissue-based injury metrics to evaluate head injury. PTA is a kinematics-based injury metric that has been suggested for predicting the risk of skull fractures and focal injuries , and it 2 threshold has been suggested for it based on the PMHS experiments  , and a 10 krad/seriments . When wery (DAI) . Marguliry (DAI) . BrIC hary (DAI) . Using try (DAI) . Again, ry (DAI) . As a reThe difference between the response of headforms under the same oblique impact conditions and using the same helmet can stem from the large difference in the coefficient of friction (CoF) at the headform/liner interface. Previous studies have shown that this CoF has significant effects on the head kinematics during oblique impact . Human sxx: 10.5%, Iyy: 2.2%, and Izz: 2.6%). The relative differences are similar or smaller than those between the 3D-printed headform and human head   . Therefo: 16.1%) .We found that the impact location influences the relationship between headform and injury metric. For example, the HIII headform produced the lowest PTA at impact 2, while for the Cellbond headform, impacts 1 and 4 produced the lowest PTA. For PRV, the lowest values occurred at impact 3 for the HIII headform and at impact 2 for the Cellbond headform. These differences may be explained by the different MoIs about the rotation axes dominant at different impact locations. Most previous studies included impact 3  and impact 4  but not impacts 1, 2, or 5, in their oblique impact tests . InteresThe gold standard for testing the fidelity of headforms is using human head kinematics under different impact conditions, but such data are currently unavailable. Alternatively, postmortem human subjects’ (PMHS) head impact data can be used . A previThis study has some limitations. We compared the performance of the Cellbond headform with that of the HIII headform only. We chose the HIII headform because it is widely used in helmet oblique impact tests and helmet rating methods . A previAnother limitation is that we tested only one helmet type. More helmet types  should be included in the future tests as helmet geometry and materials can have a large influence on the helmet performance under impact conditions. Moreover, we tested the helmets using one impact velocity with equal tangential and normal components with respect to the anvil. A recent study has shown that the tangential speed significantly affects the rotational head motion but not linear motion . Future In summary, we studied the response of the HIII headform and Cellbond headform under helmeted oblique impact conditions. The latter headform has more biofidelic MoIs and CoF, and it is an early version of the headforms under development by working group 11 of CEN/TC158. We showed that the more biofidelic Cellbond headform produced similar or higher translational acceleration than the HIII headform but significantly lower injury metrics based on head rotation and predicted strain and strain rate across the brain. This indicates that the HIII headform may overestimate the risk of brain injuries produced by head rotation. It may also not adequately assess and distinguish the performance of helmet technologies developed for mitigating such injuries. We, therefore, recommend adopting headforms with biofidelic MoIs and CoF  in future helmet standards and rating methods to better assess the protection performance of helmets.


PI-RVF can be diagnosed from the first 24–72 h after completion of heart transplantation. A total of 122 consecutive patients who underwent HTX were reviewed. Of these, 11 were excluded because of secondary causes of graft dysfunction (GD). PI-RVF was present in 65 of 111 patients (59%) and 31 (48%) met the criteria for PGD-RV. Severity of patients with PI-RVF included 41(37%) mild, 14 (13%) moderate, and 10 (9%) severe. The median onset of PI-RVF was 14 (0–49) h and RV recovery occurred 5 (3–14) days after HTX. Severe RV failure was a predictor of 30-day mortality  and post-transplant dialysis . Patients with moderate PI-RVF had a higher rate of 30-day mortality  and post-operative dialysis  than those with mild PI-RVF. Among patients with mild and moderate PI-RVF, patients who did not meet the criteria of PGD-RV had worsening BUN/creatinine than those who met the PGD-RV criteria . PI-RVF was common and can occur after 24 h post-HTX. The median RV recovery time was 5 (2–14) days after HTX. Severe PI-RVF was associated with increased rates of 30-day mortality and post-operative dialysis. Moderate PI-RVF was also associated with post-operative dialysis. A revised definition of PGD-RV may be needed since patients who had adverse outcomes did not meet the criteria of PGD-RV.To determine the prevalence, right ventricular (RV) characteristics, and outcomes of primary isolated RV failure (PI-RVF) after heart transplant (HTX). PI-RVF was defined as (1) the need for mechanical circulatory support post-transplant, or (2) evidence of RVF post-transplant as measured by right atrial pressure (RAP) > 15 mmHg, cardiac index of < 2.0 L/min/m Right ventricular PGD (PGD-RV) can cause devastating early post-transplant hemodynamic complications requiring mechanical circulatory support5. Primary isolated RV failure (PI-RVF) or PGD-RV is a condition where there is clinical and/or hemodynamic evidence of RVF in the absence of pulmonary hypertension, RV injury, and cardiac allograft rejection5. The pathogenesis of post-heart transplant RV failure is multifactorial and complex11. Although ischemia during organ preservation, a consequence of brain death and inotrope effect, and reperfusion injury leads to RV ischemic injury and RV failure, the established pathogenesis of this condition is yet to be determined13. Currently, PGD-RV is defined as right ventricular (RV) failure restricted to 24 h after surgery5. Invasive hemodynamic evidence of PGD-RV includes elevated right atrial pressure (> 15 mmHg), normal pulmonary capillary wedge pressure (PCWP) (< 15 mmHg), and low cardiac index (CI) (< 2 L/min/m2)5. Recently, Alam et al.14 proposed that the dose and duration of inotropic support can be used to stratify the severity of RV failure when CI ≥ 2.0 L/min/m2. This revised approach effectively expands the definition to include more patients with diagnostic criteria of PGD-RV. However, the limitation of this approach still exists in real world practice. First, the onset of the 24-h period is unclear as to whether it refers to the time of completion of the transplanted anastomosis or at completion of surgical chest closure. Second, delayed onset of PGD-RV beyond 24 h after surgery is not included. Third, patients with interventricular septal shift in response to RV dilatation may have mildly elevated PCWP . Accordingly, the main modification defining PI-RVF included using a pulmonary capillary wedge pressure (PCWP) cut-off < 18 mmHg and expanding time to diagnose from the first 24–72 h after completion of heart transplantation. In this study, we sought to investigate: (1) the prevalence of PI-RVF (with and without diagnostic criteria of PGD-RV) after heart transplantation, (2) RV characteristics and recovery assessed by invasive mean right atrial pressure (RAP) in patients with PI-RVF, (3) the clinical gaps between PGD-RV and PI-RVF, and (4) clinical outcomes in patients with PI-RVF.Primary graft dysfunction (PGD) is a leading cause of early mortality after heart transplantationThe study protocol was approved by the Chulalongkorn University Institutional Review Board with a waiver of written informed consent. All methods were carried out in accordance with the tenets of the Declaration of Helsinki and the ethical standard guidelines and regulations. We retrospectively reviewed consecutive patients undergoing heart transplantation from January 1, 2008, to October 31, 2021. We excluded patients with combined organ transplantation, continuation of mechanical circulatory support (MCS) from pre-transplant to post-transplant period, concomitant left ventricular PGD, and secondary graft dysfunction including acute rejection, pulmonary hypertension or pulmonary vascular disease, and intraoperative RV injury as a surgical complication. Pulmonary hypertension precluding from study eligibility was defined as pre-transplant pulmonary arterial systolic pressure > 55 mmHg, and/or transpulmonary gradient ≥ 16 mmHg, and/or pulmonary vascular resistance > 5 Wood units. Clinical laboratory data and cardiac investigation were abstracted by one investigator from the electronic hospital informative system and transplant database of the Excellent Center of Organ Transplantation (ECOT). Pre-transplant hemodynamics assessed by right heart catheterization closest to the transplant dates were reviewed.4 and were modified from the proposed revised diagnostic criteria of PGD-RV proposed by Alam et al.14  mean RAP > 15 mmHg, (2) pulmonary PCWP < 18 mmHg, (3) CI < 2 L/min/m2 or use of inotropic support, and (4) transpulmonary gradient (TPG) < 15 mmHg and/or pulmonary artery systolic pressure < 50 mmHg.All definitions were based on the International Society for Heart and Lung Transplantation (ISHLT) consensus conference report“Mild” PI-RVF was defined as: (1) mean RAP > 15 mmHg, (2) PCWP < 18 mmHg, (3) CI < 2 L/min/m2 or the condition of no inotropes or requiring low dose inotropes for < 72 h post-transplant, and (4) transpulmonary gradient (TPG) < 15 mmHg and pulmonary artery systolic pressure < 50 mmHg. Low dose was defined by the following criteria: (1) single inotrope infusion: dobutamine < 7.5 µg (mcg)/kilogram (kg)/minute (min) or milrinone < 0.5 mcg/kg/min or epinephrine < 0.02 mcg/kg/min, or (2) two inotropic infusion: dobutamine < 3 mcg/kg/min or milrinone < 0.25 mcg/kg/min or epinephrine < 0.01 mcg/kg/min14.“Moderate” PI-RVF was defined as: (1) mean RAP > 15 mmHg, (2) PCWP < 18 mmHg, (3) CI < 2 L/min/m2 or condition requiring escalating inotropic doses or inability to wean inotropes > 72 h post-transplant14, and (4) transpulmonary gradient (TPG) < 15 mmHg and/or pulmonary artery systolic pressure < 50 mmHg.“Severe” PI-RVF was defined as a need for MCS including extracorporeal membrane oxygenation (ECMO) or use of ventricular assisted device (VAD)14.onset of RV failure was determined by the time from the completion of surgical sternal closure to the onset of RAP > 15 mmHg. The peak of RV failure was determined by the time from completion of surgical sternal closure to the time of the highest RAP (> 15 mmHg). The recovery of RV failure was determined by the time from the completion of surgical sternal closure to the onset of RAP < 15 mmHg in patients who developed primary isolated RV failure. The duration of RV failure was determined by the time duration between the onset of RV failure and recovery from RV failure. The onset of RV failure was sub-classified to pattern A , pattern B , or pattern C .The 15. The adjunctive immunosuppression was comprised of oral mycophenolate sodium (MPS) 720 mg 6 h prior to the operation and two 500 mg doses of intravenous methylprednisolone intraoperatively. All patients received cyclosporine or tacrolimus, MPS, and steroids. Delayed calcineurin inhibitor (CNI) initiation after post-operative day 3 was universally implemented in all patients who received induction therapy since we found a very low incidence of > 1R ACR in the first 4 weeks post-transplant in our center. CNI-free or low-dose CNI regimen or delayed CNI initiation after 7 days post-transplant was commenced when the serum creatinine > 1.8–2 mg/dl. Post-transplant hemodynamic assessment was performed using a pulmonary artery (PA) catheter and an arterial line placed in the operating room prior to the transplant surgery in all patients. A chest radiograph combined with a good quality pressure waveform of pulmonary arterial pressure and PCWP was used to verify the position of the PA catheter tip in the intensive care unit (ICU). According to hemodynamic measurement protocols for the operating room and ICU, pressure transducers were calibrated to the zero level at the midaxillary line in the supine position before taking measurements. Mean right atrial pressure, pulmonary arterial pressure, and arterial pressure were measured and recorded every hour or more frequently if clinically indicated. PCWPs, cardiac output, CI, and systemic vascular resistance (SVR) were measured and recorded every 4 h post-operation or more frequently if clinically indicated. After 96 h post-transplant, the frequencies of those invasive hemodynamic measurements were judged on a case-by-case basis by the attending physicians. Epinephrine, milrinone, and dobutamine were the most frequently used inotropes during post-operative period. Nitric oxide or inhaled iloprost was given for RV failure in selected cases.Donor hearts were procured after brain death declaration. Heart procurement was followed by the standard protocol using cold storage (4 °C) with preservation solution  of 2000–3000 ml. All heart transplant surgical techniques were biatrial anastomoses. Before January 2014, rabbit anti-thymocyte globulin was used for induction therapy. In February 2014, low dose basiliximab was universally implemented as the institutional protocolThe maintenance immunosuppressive agents followed the standard protocol. Cyclosporine was administered orally 2–5 mg/kg/d to achieve blood trough levels of 250–275 ng/mL during week 4, 200–250 ng/mL during week 4 to month 6, and 150–200 ng/mL during month 6–12. In February 2014, tacrolimus was administered orally 0.05–0.1 mg/kg/d in place of cyclosporine to achieve blood trough levels of 10–14 ng/mL during week 4, 10–12 ng/mL during week 4 to month 6, and 10 ng/mL during month 6–12. MPS was administered orally 48 h post-transplant to maintain the dose of 1–1.5 g twice a day. Oral prednisolone was initiated at 1 mg/kg/d and then tapered to 0.5 mg/kg/d by day 7, 0.35 mg/ kg/d by week 3, and 0.1 mg/kg/d until stopping after month 6. Prophylaxis for infection included trimethoprim-sulfamethoxazole and fluconazole. A pre-emptive strategy for cytomegalovirus (CMV) treatment was applied to all patients.Endomyocardial biopsies were obtained at numerous times post-transplant .16.Death was determined by the ECOT database, medical records, death certificates, or telephone reviews. Renal replacement therapy (RRT) or dialysis was performed by short-term continuous veno-venous hemofiltration in the ICU during the post-operative period. BUN and creatinine on post-operative day 3 represented post-operative blood urea nitrogen (BUN) and creatinine (the peak/worsening RV failure occurred on post-operative day 3). Graft loss was defined as a clinical syndrome of heart failure with objective evidence of cardiac structural abnormalities assessed by echocardiogram including left or right ventricular systolic dysfunction or elevated filling pressures. Acute cellular rejection (ACR) was defined using the revised criteria. Histopathological examination for ACR was performed in accordance with the ISHLT 2005 working formulation: (i) Grade 0R: no rejection; (ii) Grade 1R: an infiltrate with only one focus of myocyte damage or none; (iii) Grade 2R: an infiltrate with multifocal myocyte damage; and (iv) Grade 3R: diffuse myocyte damage with or without edema, hemorrhage, or vasculitisP values < 0.05 were considered significant. The data were analyzed using software IBM® SPSS® statistics version 28.0.0.0 and JMP statistical software.Frequency, percentage, median, and mean ± standard deviation (SD) were employed to describe the data. The mean difference between variables were compared using a student’s t-test for variables with normal distribution, a Wilcoxon–rank sum test for variables with non-normal distribution, and Analysis of Variance (ANOVA) for variables with more than 2 groups. Categorical variables were compared using a Chi squared test or Fischer’s exact test, where appropriate. Univariate and multivariate analyses were employed to identify the pre-operative predictors of primary isolated RV failure. Adjustment factors used in the multivariate model included age, pre-operative BUN > 43 mg/dL, direct bilirubin > 1.5 mg/dl, pre-transplant PVR (Wood units), donor age, ischemic time, and induction therapy. Due to the small number of deaths in 30-day mortality and subjects with post-operative dialysis, a multivariate analysis was not performed. Kaplan–Meier curves were constructed to estimate survival or event-free survival between groups. Significant differences in survival or events were based on the log-rank test. From January 2008 to October 2021, 122 consecutive patients undergoing heart transplantation were reviewed for study inclusion. Eleven were excluded . Of the 3 patients with early rejections, one patient who had hyperacute rejection presumably due to non-HLA antigen (negative pre-transplant panel reactive antibody and retrospective crossmatch) developed it immediately in the operating room, one had grade 2R acute cellular rejection which developed at pos-operative day 7, and one had antibody-mediated rejection that developed at day 16 post-transplant. A total of 111 patients were enrolled in the study. Baseline characteristics of patients are shown in Table Of 111 study patients, 65 (59%) had post-transplant PI-RVF  h after completion of cardiac transplant surgery. Among the 65 patients with post-transplant PI-RVF, 36 (55%), 23 (35%) and 6 (9%) developed the onset of RV failure within 24 h (pattern A), between 24 and 48 h (pattern B) and after 48 h (pattern C) of completion of cardiac transplant surgery, respectively. In the subgroup of severe PI-RVF, 2 of 10 (14%) had a time to the onset of RV failure after 24 h (38 and 41 h) after completion of heart transplant surgery. In the subgroup of moderate PI-RVF, 3 patient (21%) had an onset to RV failure after 24 h after completion of heart transplant surgery. Figure Median time to the onset of PI-RVF was day 3 (2–4).The peak of elevated RAP was observed on post-operative day 5 (3–14). Resolution of RV failure within 7 days post cardiac transplantation occurred in 49 patients (75%). In the subgroup of severe PI-RVF, 4 of 10 patients (40%) had RV recovery within 7 days post-operation  had RV recovery within 7 days post-operation and 3 required post-operative dialysis  days. In the subgroup of 10 patients with post-operative MCS support (1 short-term RVAD and 9 ECMO), 2 died on MCS. Of the 8 survivors of MCS support, median duration of MCS support was 6 (3–12) days.Among all patients, the median duration of RV failure was 2 (n = 3), or PCWP of 16–17 mmHg (n = 2). Of these patients, 27 and 7 had mild and moderate post-operative RV failure, respectively. One patient died at 61 days post-transplant due to severe infection. Table mild RV failure, those who did not meet the criteria of PGD-RV had higher BUN and creatinine on post-operative day 3 than those with PGD-RV . Among the patients with moderate RV failure, those who did not meet the criteria of PGD-RV had similar BUN and creatinine on post-operative day 3 than those with PGD-RV .Of 65 patients with post-transplant PI-RVF, 34 (52%) did not meet the criteria of PGD-RV because onset of RV failure occurred after 24 h from completion of cardiac transplant surgery (n = 29), cardiac index > 2 L/min/mp = 0.019 for severe vs. moderate RV failure, p = 0.014 for moderate vs. mild RV failure)  days, there were 34 deaths (31%). At 30 days post transplantation, there was 12 deaths (11%). The causes of 30-day deaths included 3 treated infections, 1 limb ischemia associated with ECMO, 1 severe lung injury as a surgical complication, and 7 RV failures. The 30-day mortality rates for post-transplant severe, moderate, and no/mild PI-RVF were 60%, 14%, and 5%, respectively       Fig. A,B. By us) Table . There w2, and PCWP < 15 mmHg. In the patients who did not meet the criteria of mild to moderate PGD-RV, the effect of RV failure on renal function was evident in about one-third of this subgroup. Severe RV failure was an independent predictor of 30-day post-transplant mortality and post-operative dialysis. Figure In this first reported transplant cohort from Southeast Asia, post-transplant PI-RVF is prevalent and mostly occurred during the first 24 h after completion of cardiac transplant surgery. However, delayed time to onset of RV failure after 24 h post-transplantation occurred in 45% of these patients precluding these cases to be defined as PGD-RV. The peak of RV failure (RAP) achieved its highest RAP values in day 3 after transplant surgery. RV failure transiently persisted for 4 days among all patients and 6 days in the subgroup of severe RV failure requiring MCS support. Excluding patients with severe PI-RVF or severe PGD-RV, only half of patients with mild to moderate RV failure met the criteria of mild to moderate PGD-RV due to the lack of evidence of early onset RV failure, CI < 2.0 L/min/msevere PI-RVF requiring MCS (severe PGD-RV) were 59% and 9%, respectively. The prevalence of severe PI-RVF was similar to the prevalence of severe PGD-RV. Nicoara A. et al.7 reportedsevere PGD-RV present in 7% of post-transplant patients. However, PI-RVF after heart transplant surgery was more prevalent than PGD-RV. Sabatino et al.5 reported that PGD-RV was found in 17% of patients undergoing heart transplantation. The higher prevalence of PI-RVF in our study could be due to prolonged ischemic time (> 240 min) and a broader definition of PI-RVF..In the present study, the prevalence of overall PI-RVF and mild and moderate PI-RVF post heart transplantation did not meet the criteria of mild and moderate PGD-RV mostly because time to onset of RAP > 15 mmHg occurred after 24 h post-cardiac transplant surgery. In patients with severe and moderate PI-RVF, about 20% had delayed time to onset of RV failure beyond 24 h post heart transplantation. The lack of a well-defined time point after completion of the cardiac transplant surgery may influence the onset time of elevated RAP. We proposed that the onset of a significant rise in RAP should expand beyond 24 h after completion of the cardiac transplant surgery or after completion of surgical chest closure as two patients requiring MCS developed the onset of a rise in RAP at 38- and 41-h post-surgery. Additionally, another 2 patients were precluded from PGD-RV because PCWP was 17 mmHg. Both patients had severely dilated RV and small LV on echocardiography. RV dilatation and interventricular septal shift to the left that leads to a smaller LV and increased left ventricular end-diastolic pressure in an intact pericardium have been described17. Diastolic ventricular interdependence can occur with or without an intact pericardium22. This was confirmed by an experimental study by Laster SB. et al.23 who demonstrated that RV dilatation and reverse septal curvature elevated left atrial pressure immediately after ligation of right coronary artery in closed-chest dogs. We proposed the cut-off for PCWP < 18 mmHg for diagnosis of PI-RVF as the shift in interventricular septal configuration in response to RV dilatation can cause mildly elevated LV filling pressure. We agreed with a simplified criteria using the escalation of inotropic requirement or inability to wean inotrope to define moderate PGD-RV proposed by Alam A. et al.14 as there was a limitation of achieving CI < 2 L/min/m2 in the condition of multiple inotrope supports post-transplantation. Using the original criteria of PGD-RV, the prevalence of PI-RVF post-transplant or PGD-RV is likely underestimated.We found that about half of patients with 12. The pathogenesis of post-heart transplant RV failure in the absence of pulmonary hypertension are multifactorial and complex13. The postulated mechanisms of RV failure include acute ischemic-reperfusion injury with RV myocardial stunning as a consequence of the rapid surge of catecholamines and multiple cytokines after brain death, cardiac myocyte damage caused by inotropes, the alteration of cellular metabolism of cardiac myocyte during cardiac preservation in a cold storage, and reperfusion injury after completion of surgical anastomosis26. The prolonged cold ischemic time is related to altered cellular metabolism and disturbance in Na + /K + ATPase pump resulting in cellular swelling and myocardial dysfunction27. We hypothesized that cellular swelling with myocardial stunning was the key mechanism of PI-RVF in our cohort as cold ischemic time was prolonged compared with other previous studies13. In our study, the median time to onset of elevated RAP of 15 mmHg or greater was 14 h after completion of surgery and reached its highest peak value of RAP at post-operative day 3. Consistently, Sicard et al28 confirmed RV dysfunction in mice model 24–48 h post-right coronary ligation. These findings also underscored mechanistic insight of RV failure in response to RV ischemic injury. We observed that RV failure in our study were transient and persisted for 4 (median) days among all patients and 6 days in the MCS group. Similarly, Laster et al.23 previously demonstrated that RV functional recovery of greater than 50% of baseline was evident at 4 days after coronary occlusion in the closed-chest dogs. Additionally, recent studies of MCS support for RV failure or PGD showed that the median duration of MCS support, suggestive of RV recovery, was 6–7 days7. Identifying patients who are at risk and timely MCS implantation are critically vital. We found that pre-operative elevated bilirubin and being female were predictors of severe PI-RVF requiring MCS post-transplant. Our findings align with the previous studies that have shown that higher serum bilirubin and female recipient were significant predictors of severe PGD -LV and/or RV29.The right ventricular free wall is anatomically thin and vulnerable to ischemia31. We found that severe PI-RVF or severe PGD-RV was associated not only with 30-day mortality, but also with post-operative dialysis. Although mortality in moderate RV failure patients was lower than the severe PGD-RV group, worsening renal function and requirement of post-operative dialysis were still clinically significant. In our study, 2 of 7 patients (29%) with moderate RV failure who did not meet the PGD criteria also required post-operative dialysis in the absence of sepsis and contamination of CNI. Mean post-operative BUN and creatinine in patients with moderate PI-RVF was also higher than those with mild RV failure. These findings underscore that moderate PIVF may affect hemodynamics resulting in worsening renal function. Clinical significance of moderate RV failure should not be underestimated.Post-heart transplant severe RV dysfunction and severe PGD-RV are the leading cause of 30-day mortality post-transplantationThe study is limited by its retrospective nature where bias may have influenced post-transplant management strategy and clinical outcomes. The prevalence and clinical outcomes were also affected by post-transplant care protocols, donor heart preservation techniques, surgical techniques, and geographic donor allocation associated with ischemic time in a single tertiary center which may limit generalizable. The 14-year period also introduces the potential for changes in treatment delivery as technology and skill may improve and protocols execution may evolve. These factors including improved surgical skills leading to shorter ischemic time, improved organ preservation techniques minimizing RV myocyte injury, and meticulous donor selection and management ultimately affect the prevalence of RV failure. The small number of patients in each subgroup of severity of RV failure precluded additional multivariate analyses. Further studies utilizing larger patient population may help to identify predictors across the spectrum of RV failure severity. The majority of MCS supports for severe PI-RVF in our study were ECMOs. Although RAP can guide volume management in ECMO supported patients, the RAP in the light of ECMO varies and depends on the position of venous cannula and flow pressure in the right atrium, in addition to RV function per se. The RV characteristics and RV recovery in patients with severe RV failure were limited to assessment of patients who were on MCS and died on MCS. We excluded patients with continuation of ECMO use from pre-transplant period because determination of the onset of elevated RAP post-transplant may not be accurate in those with mild or mild to moderate PI-RVF in the presence of ECMO. Additionally, pulmonary pressure was limited to assess in those patients. Lastly, the measurement of post-operative hemodynamic parameters was not validated for intra- and inter-observer variation These parameters were recorded by intensive care unit nurses as per clinically indicated protocol and were subjected to vary.Primary isolated RV failure was common after heart transplantation and characterized by transient and progressive RV functional deterioration occurring immediately or after 24 h post-transplant. The mean time to the highest RAP/peak RV failure was observed on post-operative day 3. The recovery of RV failure mostly occurred within 7 days after transplantation. These findings may represent transient and progressive swelling and stunning of RV myocardium as a consequence of ischemic-reperfusion injury in the first few days after heart transplantation. Despite this transient phenomenon, life threatening RV failure or severe RV failure requiring MCS occurred in about 10% of all cardiac transplantations and was associated with 30-day mortality and a need for dialysis post-transplant, while moderate isolated RV failure was associated with post-transplant worsening renal function and requirement of dialysis. A revised definition of PGD-RV to capture more patients with significant RV failure may be needed since those patients in our study who had adverse outcomes did not meet the criteria of PGD.


Intravenous iron treatment versus standard care in patients with heart failure and iron deficiency (IRONMAN) trial evaluated whether the benefits of intravenous iron persist in the longer term and impact on morbidity and mortality.For patients with a reduced left ventricular ejection fraction (LVEF) heart failure with reduced ejection fraction (HFrEF) and iron deficiency, administration of intravenous iron improves symptoms, exercise capacity and may in the following 12 months, reduce hospitalisations for heart failure. The Effectiveness of IRONMAN is a prospective, randomised, open-label, blinded endpoint (PROBE) event-driven trial. Patients aged ≥18 years with HFrEF (LVEF ≤45%) and evidence of iron deficiency (ferritin <100 µg/L and/or TSAT <20%) were enrolled if they had either a current or recent hospitalisation for heart failure or elevated plasma concentrations of a natriuretic peptide. Participants were randomised to receive, or not to receive, intravenous ferric derisomaltose in addition to guideline-recommended therapy for HFrEF. Every 4 months, intravenous iron was administered if either ferritin was <100 µg/L or, provided ferritin was ≤400 µg/L, TSAT was <25%. The primary endpoint is a composite of total hospitalisations for heart failure and cardiovascular death. Hospitalisation and deaths due to infection are safety endpoints.Trial recruitment was completed across 70 UK hospital sites in October 2021. Participants were followed until the end of March 2022. We plan to report the results by November 2022.IRONMAN will determine whether repeated doses of intravenous ferric derisomaltose are beneficial and safe for the long-term treatment of a broad range of patients with HFrEF and iron deficiency.NCT02642562. In patients with heart failure and reduced ejection fraction and associated iron deficiency, treatment with intravenous iron can improve symptoms, exercise capacity and may reduce hospitalisation for heart failure, in the following 12 months.Intravenous iron treatment versus standard care in patients with heart failure and iron deficiency (IRONMAN) is a randomised trial, powered to determine whether repeated doses of intravenous iron  are beneficial and safe in the long term in a broad range of patients with heart failure and reduced ejection fraction. The primary endpoint is a composite of total hospitalisations for heart failure and cardiovascular death.Effectiveness of The results of IRONMAN will help to inform clinical practice and international guidelines with respect to the management of iron deficiency in patients with heart failure and reduced ejection fraction.Iron is an essential component of haemoglobin, myoglobin, the mitochondrial electron transport chain and many enzymes. Patients with heart failure, with or without reduced left ventricular ejection fraction (LVEF), often have anaemia, and this will usually be due to iron deficiency.Placebo-controlled studies have demonstrated that intravenous administration of ferric carboxymaltose in ambulatory patients with heart failure and reduced LVEF (HFrEF) improves exercise capacity, symptoms and quality of life (QoL).Intravenous iron treatment versus standard care in patients with heart failure and iron deficiency (IRONMAN) trial was designed and conducted in the UK to investigate the benefits and safety of repeated doses of intravenous ferric derisomaltose over an extended period, which should help inform clinical practice and international guidelines.Major gaps in our knowledge remain, including the long-term benefits and safety of repeated administration of intravenous iron. Although the rationale for benefit is clear, bypassing evolutionary systems that have evolved to prevent iron overload also poses theoretical risks, including increased oxidative stress, mitochondrial damage and infection.IRONMAN is a prospective, randomised open-label, blinded endpoint (PROBE) event-driven trial designed to assess the efficacy and safety of intravenous ferric derisomaltose in symptomatic patients with HFrEF and iron deficiency. The endpoints committee adjudicating events are kept blinded to assigned treatment.Patients aged ≥18 years with new or established symptomatic HFrEF (LVEF ≤45% within the preceding 24 months) were invited to participate. Iron deficiency was defined as serum ferritin <100 µg/L and/or TSAT <20%. In addition, patients either had to have a current or recent (<6 months) admission for heart failure (including daycare intravenous diuretics) or have increased plasma concentrations of a natriuretic peptide  ≤45% within the last 2 years using any conventional imaging modality (most recent assessment)NYHA class II–IVIron deficient – defined as transferrin saturation (TSAT) <20% and/or ferritin <100 ug/L.Evidence of being in a higher risk heart failure group:Current or recent (within 6 months) hospitalisation for heart failure.Outpatients with NT-proBNP >250 ng/L in sinus rhythm or >1000 ng/L in atrial fibrillation .Able and willing to provide informed consent.Haemoglobin <9 g/dL or 13 g/dL in women or >14g/dL in men.Ferritin >400ug/L.2 (MDRD/CKD-EPI).eGFR <15 mL/min/1.73 mAlready planned to receive intravenous iron.Likely to need or already receiving erythropoiesis-stimulating agents.Blood transfusion in the previous 3 months or active clinically relevant bleeding in the investigator’s opinion or known or suspected gastrointestinal malignancy.Planned cardiac surgery or revascularisation.Any major vascular event in the previous 3 months, including type 1 myocardial infarction, cerebrovascular accident, major cardiovascular surgery or percutaneous coronary intervention.Awaiting or treated by cardiac transplantation or left ventricular assist device.Active infection .Any disease other than heart failure with a life expectancy of <2 years.Pregnancy, breast feeding or childbearing potential in the absence of effective contraception.Contraindication to intravenous iron according to contemporary Summary of Product Characteristics including hypersensitivity to Monofer ® or any of its excipients; known serious hypersensitivity to other parenteral iron products; anaemia due to causes other than iron deficiency ; iron overload or disturbances in utilisation of iron ; and decompensated liver disease.Participation in another intervention study involving a drug or device within the past 90 days .BNP, B-type natriuretic peptide; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; eGFR, estimated glomerular filtration rate; LVEF, left ventricular ejection fraction; MDRD, modification of diet in renal disease; NYHA, New York Heart Association; NT-proBNP, N-terminal pro B-type natriuretic peptide.2. Iron deficiency is less common when haemoglobin is more than 1 g/dL above the WHO definition of anaemia. Accordingly, to reduce screen failures, men with a haemoglobin >14 g/dL and women with values >13 g/dL were excluded. A detailed list of inclusion and exclusion criteria is shown in Patients were excluded if they had high ferritin (>400 µg/L), a haemoglobin <9.0 g/dL or an estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 mAn overview of the trial is shown in 10.1136/heartjnl-2022-321304.supp1Supplementary dataConsenting and eligible patients were randomised with equal probability to the two treatment arms, stratifying by recruitment context  and trial site, using a web-based system based on randomised, permuted blocks of variable size.Participants assigned to intravenous iron were administered ferric derisomaltose by infusion at a dose determined by haemoglobin value and body weight . At eachA key goal was to try and ensure that those assigned to intravenous iron were kept iron replete, with redosing with intravenous ferric derisomaltose at the 4-week review and every 4 months after randomisation if either the ferritin was <100 µg/L or, provided ferritin was ≤400 µg/L, TSAT was <25%. If iron deficiency recurred, investigators were encouraged to consider further investigations for potential sources of blood loss. Oral iron supplementation was permitted at the discretion of the investigator in the standard care arm. Any use of non-trial iron supplements was recorded.The data collected at each timepoint varied, with more in-depth assessment taking place at randomisation, 4 and 20 months . This inThe primary and secondary efficacy endpoints are summarised in Box 2Cardiovascular (CV) mortality or hospitalisation for worsening heart failure Hospitalisation for worsening heart failure (recurrent events).CV hospitalisation (first event)CV death or hospitalisation for heart failure analysed as time to first event.Overall Score from Minnesota Living with Heart Failure at 4 months.Cardiovascular mortality.Overall EQ-5D visual analogue score (VAS) at 4 months.Overall EQ-5D index at 4 months.CV mortality or hospitalisation (first event) for major CV event including: stroke, myocardial infarction and heart failure.All-cause mortality.All-cause hospitalisation (first event).Combined all-cause mortality or first all-cause unplanned hospitalisation.Physical domain of Minnesota Living With Heart Failure at 4 months.Physical domain of Minnesota Living With Heart Failure at 20 months.Overall EQ-5D VAS at 20 months.Overall EQ-5D index at 20 months.Overall Score from Minnesota Living with Heart Failure at 20 months.Days dead or hospitalised at 3 years.Quality-adjusted days alive and out of hospital at 12 months.Six minute walk test at 4 months.Six minute walk test at 20 months.Death due to infection.Hospitalisation primarily for infection.Investigators are asked to report serious adverse events (SAEs). This does not include routine treatment or monitoring of heart failure; elective or preplanned treatment for a pre-existing non-cardiac condition; any admission for general care without deterioration in health; and treatment on an emergency, outpatient basis for an event not fulfilling the definition of an SAE.All emergency day-case treatments for heart failure or elective percutaneous coronary intervention or cardiac device insertion are to be recorded as SAEs. Investigators are expected to report all blood transfusions and any important bleeding event, even if it does not require hospitalisation or was not life threatening. Death due to infection and hospitalisation due to infection are secondary safety endpoints.Record linkage to national databases of deaths, hospital admissions and incident cancers is planned at the end of the trial in England and Scotland and for deaths in Wales to ensure complete reporting of events.Sample size calculations based on recurrent event analyses are difficult  conducted interim analyses of the primary endpoint when approximately 50% and 70% of the target number of first primary endpoints had been reached, requiring p<0.001 to recommend early stopping.et alThe primary endpoint will be analysed by the method of Lin Secondary endpoints will be analysed hierarchically in the order shown in Secondary endpoints involving recurrent events will be analysed as for the primary endpoint. Time to first event outcomes will be analysed using Cox proportional hazards models including treatment effect and recruitment context, with the treatment effect HR and 95% CIs estimated with associated p values using the Wald statistic and treatment groups compared graphically using cumulative incidence functions.QoL scores and 6 min walk tests results at 4 and 20 months will be compared between randomised treatment groups using analysis of covariance, with treatment group and stratification variable as covariates.Subgroup analyses will be carried out for the primary endpoint, analysed as a recurrent event and then separately as time-to-first event.A formal Statistical Analysis Plan will be finalised before trial database lock.In practice, we recruited mainly outpatients who had a lower rate of events; recruitment was slower than expected, especially during the COVID-19 pandemic, which also may have reduced cardiovascular admissions, resulting in a lower event rate for the primary endpoint. This, in combination with likely patient and investigator fatigue, led the Trial Steering Committee (TSC) to revise the power calculation for the trial. Assuming an HR of 0.75, as in AFFIRM-AHF trial,Analyses based on patients randomised until the end of March 2020 with a censoring date of 30 September 2020 will be carried out to assess the impact of the COVID-19 pandemic on the results.National Health Service Greater Glasgow and Clyde and the University of Glasgow are cosponsors for the trial, supported by the Glasgow Clinical Trials Unit with trial data and statistical centre in the Robertson Centre for Biostatistics, University of Glasgow.Four committees were established to oversee the trial delivery  Greater Glasgow and Clyde and the University of Glasgow. Four committees have been established to oversee the trial delivery : the TSC includes an independent chairperson, at least two other independent members, a representative from the British Heart Foundation and a patient representative. The TSC provides overall supervision of the trial, ensuring it is conducted in accordance with the principles of Good Clinical Practice (GCP) and the relevant regulations. The TSC is responsible for approving the trial protocol and any protocol amendments.Independent Data Monitoring Committee (IDMC): the IDMC consists of three independent experts  and is responsible for overseeing trial conduct, conducting interim analyses and monitoring patient safety.Clinical Endpoint Committee (CEC): the CEC carry out blinded assessment of all clinical events identified as potentially relevant to the designated secondary health outcomes. This included blinded adjudication of all hospitalisations and deaths.Trial Management Group (TMG): the TMG comprises the chief investigator, other coapplicants, project manager and sponsor representatives and meet frequently to monitor all aspects of trial conduct and progress and to ensure protocol adherence.Patients were involved at all stages of trial design, including membership of the TSC.Participants were enrolled in UK centres from August 2016 to October 2021 . Total dose replenishment was given whenever possible. From a healthcare provider (and patient) perspective, correction of iron deficiency with a single high-dose infusion is attractive. The trial will provide data on longer term iron requirement for patients receiving optimal guideline-directed treatment.While oral iron was permissible in the standard of care arm, IRONMAN is not designed to determine if intravenous iron is better than oral iron.Although AFFIRM-AHF and IRONMAN enrolled similar numbers of patients, follow-up was for 12 months in AFFIRM-AHF and will be considerably longer in IRONMAN, up to 5.6 years. It is plausible that the relatively short follow-up in AFFIRM-AHF impacted on the finding that there was no obvious effect of intravenous iron on cardiovascular death ; p=0.69).Although blinding is normally an important part of trial design, there are occasions where it is very difficult to implement. Iron infusions are dark brown, and there are few placebo alternatives. Ensuring a patient does not see what is going into their arm is difficult. It is even harder to blind the investigator, who should not be aware of the haemoglobin, blood tests for iron deficiency or what the participant will receive. This requires blinded and unblinded teams at every centre. Feedback from research teams and patient representatives was that this was unrealistic. As such, IRONMAN incorporated a PROBE design. For studies where the primary endpoint is QoL or exercise capacity, blinding is essential. Outcomes such as heart failure hospitalisation and cardiovascular death are less prone to bias when adjudicated blindly by an independent committee, as in IRONMAN.Inevitably, COVID-19 will have influenced the IRONMAN trial. Some participants will have had COVID-19 infections, and some will have died from COVID-19. Visits to research clinics were curtailed during the pandemic, and therefore, assessing patients for recurrent iron deficiency and redosing with iron was impossible at times. There has been a reduction in hospitalisations for heart failure in the UK, as in many other countries, during the pandemic.The primary endpoint in IRONMAN includes recurrent hospitalisation for heart failure. It has been proposed that this is the most clinically relevant endpoint for patients with heart failure, capturing the total impact of treatment.There are theoretical risks associated with repeated intravenous iron dosing. Labile (free) iron can result in the generation of reactive oxygen species, which could lead onto oxidative stress and cell damage.Two other ongoing randomised outcome trials of intravenous ferric carboxymaltose include patients with HFrEF: HEART-FID10.1136/heartjnl-2022-321304.supp5Supplementary dataIRONMAN will help clarify the long-term efficacy and safety of intravenous ferric derisomaltose in a broad range of patients with HFrEF.


To develop and validate clinical evaluators that predict adverse left ventricular remodeling (ALVR) in non-ST-elevation myocardial infarction (NSTEMI) patients after primary percutaneous coronary intervention (PCI).n = 287), and the remaining patients (n = 220) were assigned to an external validation cohort. The endpoint event was the occurrence of ALVR, which was described as an increase ≥ 20% in left ventricular end-diastolic volume (LVEDV) at 3–4 months follow-up CMR compared with baseline measurements. The occurrence probability of ALVR stemmed from the final model, which embodied independent predictors recommended by logistic regression analysis. The area under the receiver operating characteristic curve (AUC), Calibration plot, Hosmer–Lemeshow method, and decision curve analysis (DCA) were applied to quantify the performance.The retrospective study analyzed the clinical data of 507 NSTEMI patients who were treated with primary PCI from the Affiliated Hospital of Xuzhou Medical University and the Second Affiliated Hospital of Xuzhou Medical University, between January 1, 2019 and September 31, 2021. The training cohort consisted of patients admitted before June 2020 (P = 0.514) and the validation set (P = 0.762) and the probabilities of actual occurrence. DCA corroborated the clinical utility of the nomogram.Independent predictors for ALVR included age (odds ratio (OR): 1.040; 95% confidence interval (CI): 1.009–1.073), the level of neutrophil to lymphocyte ratio , the cardiac microvascular obstruction , peak global longitudinal strain , infarct size  and left ventricular ejection fraction , which were screened by regression analysis then merged into the nomogram model. Both internal validation (AUC: 0.805) and external validation (AUC: 0.867) revealed that the prediction model was capable of good discrimination. Calibration plot and Hosmer–Lemeshow method showed high consistency between the probabilities predicted by the nomogram (In this study, the proposed nomogram model enabled individualized prediction of ALVR in NSTEMI patients after reperfusion and conduced to guide clinical therapeutic schedules. More than 7 million patients with new-onset myocardial infarction on a global scale each year, which holds a serious negative impact on human health . PercutaALVR is a complex process that brings about a range of irreversible changes in the structure and function of the cardiovascular system in response to some physiological and pathological stimuli . At presNomogram, a graphical form of the clinical prediction model, can calculate the probability of an event quantitatively . As a reThis study was conducted by the Declaration of Helsinki and was approved by the Medical Research Ethics Committee of the Affiliated Hospital of Xuzhou Medical University. All clinical information involved for retrospective analysis were available from the Affiliated Hospital of Xuzhou Medical University and the Second Affiliated Hospital of Xuzhou Medical University. 742 consecutive patients with first-onset NSTEMI hospitalized between January 1, 2019 and September 31, 2021 were initially included. Patients who conformed to all the following conditions were collected: (1) Patients were diagnosed with NSTEMI by relevant guidelines and received primary PCI successfully (TIMI grade ≥ 2 after PCI) within 24 h; (2) Patients received cardiac magnetic resonance (CMR) within 7 days after revascularization. Exclusive criteria: (1) Medical history of myocardial infarction or coronary artery bypass grafting; (2) Patients with one of the following complications: severe liver or kidney disfunction, malignant tumour, acute infection, severe haematological disorder, autoimmune disease, congenital heart disease, malignant arrhythmia, rheumatic heart disease, Killip class III or IV; (3) Patients lost to follow-up.Ultimately, 507 patients were included in this study. 287 patients admitted before June 1, 2020 were assigned to the training cohort, and 220 patients admitted after May 31, 2020 were splitted into the validating cohort. The nomogram was established and validated through the training and validation groups, respectively. Patient enrollment and study design were shown in Fig. All patients were administered the loading dose of 300 mg aspirin, 600 mg clopidogrel or 180 mg ticagrelor before the procedure, exclusive of those who had received dual antiplatelet therapy (DAPT) one week before the operation. Therapeutic schedule: all patients underwent coronary angiography and then underwent PCI or drug conservative treatment according to the characteristics of coronary lesions and the attitudes of patients’s families. The selection of interventional equipment and adjuvant drugs  were determined by operators on the basis of the specific situation of each patient. After the operation, all patients were treated with DAPT in accordance with the related guidelines, β-blockers, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, statins, nitrates, aldosterone antagonists and other drugs, as appropriate.CMR imaging was performed with a 3.0-T MRI Scanner  within 7 days and 3–4 months after primary PCI, equipped with a 5-unit cardiac coil, electrocardiographically-gated technique, and a dual-channel high pressure injector. Patients remained in supine position, and images were captured while the patient was holding his breath at the end of a calm exhalation. Cine Imaging: free steady-state fast gradient echo (BTFE) sequence, continuous scanning from apex of the LV to base and three long-axis planes  to assess cardiac function and volume. Black Blood Imaging: T2-weighted short-tau inversion recovery (T2-STIR) sequences, scanned covers the entire left ventricular short-axis to evaluate compositional changes in myocardial tissue. Perfusion imaging: Dynamic SENSE-TFE sequences, scanning left ventricular short-axis position while Gd-DTPA  was injected intravenously. Late gadolinium enhancement (LGE) images were captured 15–20 min after contrast injection through the phase-sensitive inversion recovery (PSIR) sequence. The scanning parameters: echo time 1.4 ms, repetition time 2.30 ms, section thickness 8 mm, the field of view 350 * 350 mm.CMR cine images post-processing were performed with CVI software  by two senior radiologists independently. The functional parameters of the left ventricle were obtained by analyzing the Cine sequence (short-axis portion) using the LAX module of the software. Cine images of the short and long axes were analyzed by the Strain module to access strain parameters. Semi-automatic delineation of the LV endocardial and epicardial borders was performed in each section at end-diastole, then manually corrected according to the morphological features if necessary. Peak global strain values were obtained by analysis, including peak global circumferential strain (GCS), peak global radial strain (GRS), and peak global longitudinal strain (GLS). The collected CMR delayed enhancement sequences were analyzed using the Tissue Signal Intensity module. The area of delayed enhancement was showed as the high signal area consistent with the distribution of culprit vessels on the LGE image, that was, an area where the signal intensity is greater than 5 standard deviations (SD) of normal myocardial signal . The totBy reviewing the electronic medical records, those patients who completed the evaluation of electrolytes, liver and kidney function, electrocardiogram, and CMR within 3–4 months after PCI were considered to be successfully followed up. The clinical endpoint was the occurrence of ALVR, which was described as an increase ≥ 20% in left ventricular end-diastolic volume (LVEDV) at 3–4 months follow-up CMR compared with baseline measurements , 24.Assembled clinical data through electronic medical records, covering demographic information, physical examination data, laboratory parameters, treatment strategies  and correlative indices of CMR.Demographic information were comprised of sex, age, smoking or drinking history, pre-infarction angina (pre-AP), and Killip class. Physical examination results consisted of body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR). The past medical history contained hypertension, diabetes, coronary artery disease (CAD), and a history of stent implantation. Laboratory parameters included hemoglobin (HGB), white blood cell (WBC) count, platelet (PLT) count, Neutrophil to Lymphocyte Ratio (NLR), total cholesterol (CHOL), low-density lipoprotein cholesterol (LDL-C), lipoprotein a, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), lactate dehydrogenase (LDH), creatine kinase isoenzyme (CKMB), high-sensitivity troponin T (hsTnT), cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), serum creatinine (CREA), serum uric acid (UA), hemoglobin A1c (HbA1c), and high-sensitivity C-reactive protein (hsCRP). All baseline laboratory indicators were first results of laboratory test within 24 h of admission. Treatment strategies contained symptom onset-to-balloon time (SBT), Multivascular disease, left anterior descending branch (LAD), left circumflex branch (LCX), right coronary artery (RCA), non-culprit chronic total occlusion (CTO), door-to-balloon time (D2B), the number of stents, no-reflow, and the use drug of atropine, dopamine, tirofiban, and nitroprusside. CMR parameters included LVEDV, left ventricular end-systolic volume (LVESV), IS, cardiac output (CO), left ventricular ejection fraction (LVEF), CMVO, IMH and strain values GCS, GRS, and GLS.P-values < 0.05 in multivariate logistic regression analysis, and the performance  was assessed. We used bootstrap method for internal validation, with resampling times B = 1000. The concordance index (C-index) is a common measure of discrimination, and the area under the curve (AUC) determined by the receiver operating characteristic curve (ROC) was utilized to represent C-index in this study. The calibration plot and Hosmer–Lemeshow method were performed to observe the consistency between the predicted and the actual probabilities. In addition, Decision-curve analysis was applied to appraise the clinical utility. In all analysis, with P < 0.05 (two-sided test) as the difference was statistically significant. All data were analyzed by R Studio software (version 4.1.3) and Stata software (version 16.0).Restricted cubic spline was performed to analyze linear relationships between all candidate continuous variables and ALVR. Categorical data are displayed as the frequency with percentage and checked by chi-square test for comparison. The Continuous indicators that conformed to normal distribution were expressed as mean ± standard deviation (x ± s), using the t-test. Continuous data that did not conform to a normal distribution were expressed as medians (quartile) M  and compared by the Mann–Whitney U test. Univariate logistic regression analyses were undertaken to screen the potential risk factors of ALVR in NSTEMI patients who had post-PCI, and the variables with significant differences were further selected into multivariate logistic backward stepwise regression analysis. The nomogram was developed based on the variables whose n = 287) and the external validation group (n = 220). 143 patients were diagnosed with ALVR by re-examining CMR, including 77 (26.80%) in the training team and 66 (30.00%) in the validation team. The differences in baseline characteristics between the two groups were not statistically significant, which showed good comparability   Table . After t5) Table .Table 2UA nomogram model was developed based on six factors  correlated with ALVR, according to the univariate and multiple logistic regression analysis Fig. . RegardiP > 0.05). The calibration plots indicated a high consistency between the nomogram  for the nomogram was 0.805 (95% CI: 0.743–0.860) in the development cohort and 0.867 (95% CI: 0.812–0.914) in the test cohort by the receiver operating characteristic (ROC) curve, which demonstrated an outstanding discrimination  was used to appraise the applicability and benefit of the model in two datasets. The nomogram showed superior clinical application value when the threshold probability was between 0.05 and 0.80 in training and external validating cohorts (Fig. In this study, we aimed to develop and verify a practicable and straightforward tool to predict the probability for the occurrence of ALVR in NSTEMI patients after reperfusion. Based on logistic regression analysis, age, NLR, IS, EF, GLS and CMVO, six factors were ultimately incorporated into the nomogram model, which consisted of cardiovascular risk factor and imaging data. After that, the nomogram showed excellent performance by verification from three aspects: discrimination, calibration, and clinical utility.Molecular, cellular and interstitial changes during the period from the acute occlusion of coronary artery to ALVR, eventually leading to heart failure . There iIt is well known that some factors, such as advanced age, IS, and LVEF, have been recognized as risk factors for poor outcomes after AMI –27, our Extensive studies revealed that strain, correlating with IS and infarct mass, demonstrated independently prognostic values in AMI patients , 30–34. ALVR results from the interaction between persistent and dysregulated inflammation and immunoreaction after acute myocardial ischemia. The increase in N count suggests the severity of inflammatory reaction, and the decrease of L count prompts the intensity of stress response . TherefoIn this study, we speculated that sex, the level of hsTnT, and Multivascular disease had a strong association with ALVR, not the independent risk factors for it. It is not gender but sex hormones that protect the cardiovascular system through neurohumoral regulation. The composition of sex hormones will change along with growing older, and we didn´t carry out an age-adjusted subgroup analysis for gender. As we know, troponin is the biomarker for detecting myocardial injury, and their concentrations change dynamically with with the duration of myocardial ischemia. Partial reports found that peak hsTnT was the marker of the MACE in MI patients undergoing PCI, but the data we collected was at admission, not at peak concentration.Firstly, the selection bias inherent is inevitable on account of the small sample and retrospective study. Secondly, patients within NSTEMI undergoing primary PCI were not a random sample from the china population. Therefore, it is necessary to perform additional validation of our results with large-scale and multi-center data.In this predictive study, the clinical calculating tool provided more customized estimators of the likelihood of ALVR in NSTEMI patients by integrating six independent prognostic factors, including Age, NLR, IS, EF, GLS and CMVO. These estimates contribute to prognostic risk stratification early in clinical management.


Prolonged and intensive exercise induces remodeling of all four cardiac chambers, a physiological process which is coined as the “athlete’s heart”. This cardiac adaptation, however, shows overlapping features with non-ischemic cardiomyopathies, such as dilated, arrhythmogenic and hypertrophic cardiomyopathy, also associated with athlete’s sudden cardiac death. Cardiac magnetic resonance (CMR) is a well-suited, highly reproducible imaging modality that can help differentiate athlete’s heart from cardiomyopathy. CMR allows accurate characterization of the morphology and function of cardiac chambers, providing full coverage of the ventricles. Moreover, it permits an in-depth understanding of the myocardial changes through specific techniques such as mapping or late gadolinium enhancement. In this narrative review, we will focus on the certainties and uncertainties of the role of CMR in sports cardiology. The main aspects of physiological adaptation due to regular and intensive sports activity and the application of CMR in highly trained athletes will be summarized. Cardiac adaptation due to regular and intense exercise is a well-known phenomenon leading to symmetric hypertrophy and volumetric adaptation summarized by the term “athletes’ heart” . The intCritically, these diseases are among the most important underlying alterations leading to rare  but tragic and highly publicized events of sudden cardiac death (SCD) among young athletes ,4. AlthoCardiac magnetic resonance (CMR) imaging metrics show high reproducibility and the method is well-suited to differentiate physiological adaptation from pathological alterations . CMR allTo distinguish between physiological and pathological remodeling with high precision, we must establish what normal means within the context of the athlete’s heart. Therefore, we summarize the main aspects of physiological adaptation due to regular and intensive sports activity. Second, we describe the main application of CMR in highly trained athletes. Finally, we provide an overview of critical gaps in the literature.The first description of cardiac dilatation and hypertrophy due to sports activity in cross-country skiers using percussion goes way back to the dawn of the 19th century ,8. The iThe cine CMR sequence has been established as the gold-standard method for quantification of ventricular volumes, function and myocardial mass in the general population ,10,11,12Cardiac morphology, function and adaptation to exercise changes with age ,15. In tCousergue et al. demonstrated a strong relationship between age-induced changes in LV diastolic function and left atrial (LA) function in healthy young (<35 years) and master (>35 years) athletes using echocardiography . ImportaDespite female athletes taking up to half of the whole athletic population , the carCsecs et al. on the other hand, examined 327 healthy Caucasian athletes using CMR, including 85 (26%) female athletes to investigate the influence of age, sex, body size, sporting type and training volume on cardiac size and function . They foIndeed, while the overall size of male athlete’s heart is clearly more enlarged than the female’s, the differences in the relative volumetric and mass changes induced by sports activity are still inconclusive .Data regarding ethnic differences using CMR is scarce, despite the well-documented impact of origin on the cardiovascular response to high intensity exercise . In the Black athletes present predominantly similar exercise-related adaptation as white athletes, however they generally demonstrate an increased LV wall thickness and a more concentric pattern of hypertrophy compared to white athletes ,33. RidiCritically, echocardiography data from Malhotra et al.  shows thAs per the 2020 ESC guidelines, we can differentiate between athletes based on level of sports activity and the type of sports they perform . CompariThe differences between sports disciplines are also widely studied, however, it is rather challenging to compare exercise-type related remodeling owing to the differences in the classification of sports in the literature ,39,40. IIn contrast, D’Ascenzi reported that RV volumes and LV mass were independent of sports discipline in their meta-analysis . Of noteAlthough it is very well known that different contouring approaches have an important impact on cardiovascular measures , no studThe right ventricular insertion points (RVIP) to the anterior and posterior ventricular septum, also known as hinge points, are zones of transition where RV and LV muscular fibers cross each other. In these areas, the presence of isolated focal myocardial disarray has been demonstrated thanks to autopsy studies conducted on hearts with HCM ,45. SubsThe reason why RVIP can present myocardial disarray is still a matter of debate. Given their location and configuration, RVIP seem to be particularly sensitive to ventricular pressure overloading. It has been demonstrated in animal models that a raised RV wall stress for increased pressure loading may lead to incremental biventricular fibrosis, predominantly involving the septal hinge points, probably involving increased growth factors signaling, predominately expressed at the level of RVIP ,49.Beside histopathology, the presence of an altered myocardial tissue at ventricular interceptions has also been demonstrated by imaging. LGE confined to isolated RVIP  is a common finding on CMR imaging. It has raised interest since its first identification in HCM patients, among whom focal fibrosis in the insertion points has been reported in at least 10% of cases ,51. HoweHinge point LGE has also been described in other clinical conditions characterized by RV overload . InteresWhile LGE imaging is able to evaluate advanced stages of remodeled myocardial tissue, early stages of RVIP disarray may be more subtle and difficult to detect. Newer imaging techniques such as T1-mapping techniques may be more sensitive for the identification of such changes ,56.Beyond these considerations, hinge point LGE is also a common finding in healthy subjects with otherwise normal CMR findings and seems to have no prognostic implications . FurtherHighly trained endurance athletes  showed aEmerging CMR techniques including native T1 and T2 mapping, have become more widely available in recent years, offering new opportunities for the non-invasive identification of various cardiac pathologies . Native In spite of the successful application of the technique for various differential diagnostic questions, the sex, ethnicity and training dependence of native T1 and T2 mapping values remain incompletely understood . It is aNative T1 mapping is generally slightly decreased among young, healthy athletes ,68,69,70Notably, limited studies have already demonstrated the additional value of native mapping sequences to better differentiate pathological alterations compared to standard volumetric measures based on cine images. In a small proof-of-concept study, Gastl et al. demonstrated that T2 mapping and deformation imaging may help distinguish left ventricular hypertrophy caused by physiological remodeling due to sports activity and pathological from due to HCM . SimilarMapping alterations were widely reported in studies investigating the myocardial involvement after SARS-CoV-2 infection in athletes ,77,78,79Competitive athletes are a growing population, often (erroneously) considered as “immune” to cardiovascular diseases. Conversely, vigorous physical activity might increase the risk for adverse events up to SCD, especially among subjects with concealed cardiovascular diseases .In the last few years, shared recommendations and pragmatical approaches on athletes’ evaluation have been provided, to distinguish between normality and abnormality ,84,85. AHCM is one the leading cause of SCD among young athletes , and itsNotably, the current cut-off values for the diagnosis of HCM are based on echocardiographic, and not CMR, studies. However, when measuring the interventricular septum by echocardiography it is common to wrongly include RV trabeculae, thus overestimating septal thickness. Another ambiguous region is the LV apex, where focal hypertrophy can frequently be unrecognized ,89,90 F. For a mECV is typically decreased in athlete’s heart and increased in HCM ,93. MoreContrast-enhanced CMR has been applied to HCM both as an adjunctive diagnostic technique and as a tool for SCD risk stratification ,94,95. LCMR is used for risk stratification according to the 2020 ESC Guidelines on sports cardiology. Importantly, the presence of extensive (≥15% of LV myocardium) LGE may identify individuals at increased risk of ventricular tachyarrhythmias and SCD ,99,100. Enlargement of LV cavity is a part of the expression of cardiac adaptation to intense exercise, particularly that with high isotonic/dynamic components. The entity of LV dilatation should therefore be interpreted considering the sports discipline, the body size, the contextual LV hypertrophy, and the harmonic dilatation of the other cardiac chambers . Up to 4Echocardiographic parameters such as diastolic indexes, strain analysis, LV wall thickness and ejection fraction (at rest and during stress), along with family history, ECG, evaluation of arrhythmias, are the basic diagnostic tools . CMR canRecently, the myocardial deformational mechanics by feature-tracking CMR (FT-CMR) have been proposed as an aid in the distinction between adaptation to exercise and pathological dilatation, since DCM has different deformational characteristics as compared to both sedentary and athletes hearts . MoreoveThe main additional value of CMR in this field is the evaluation of fibrosis. The presence of nonischemic LGE  is more consistent with DCM, even if the absence of LGE does not exclude the disease  Figure . LGE mayArrhythmogenic cardiomyopathy (ACM) is one of the leading causes of SCD in athletes; moreover, it is well known that intense and repetitive exercise training can accelerate and worsen the course of the disease . The diaThe new diagnostic criteria for ACM  requiresStructural evaluation is crucial for the diagnosis of ACM regardless of the exercise level since the disease is characterized by a fibrous (or fibro-fatty) replacement of myocardium. LGE is observed in the majority of cases of ACM. The typical pattern of LGE in left-variant ACM is a subepicardial stria involving more commonly the lateral or infero-lateral wall; concomitant fatty infiltration is often observed in the same regions, even if it is neither specific nor necessary for the diagnosis ,117 Fig. The assRecently, RV strain analysis with FT-CMR has been applied to the field of athletes with suspected ACM, demonstrating good discrimination between athlete’s heart and right-ventricular ACM .An isolated non-ischemic left ventricular scar (NLVS) is defined as the presence of LGE with a non-ischemic pattern in the LV myocardium in the absence of other distinctive signs of cardiomyopathy. It is an emerging substrate of ventricular arrhythmias and SCD occurring during effort ,121,122.CMR offers the possibility of identifying myocardial fibrosis even where other techniques fail. Indeed, since non-ischemic scar by definition spares the endocardium, no wall motion abnormalities or systolic dysfunction are seen, except in cases of extensive scar replacement . ECG abnIn caseswe of an inflammatory etiology of the NLVS, CMR also offers the possibility to display the presence of myocardial edema thanks to T2-weighted sequences and T2 mapping technique indicating an ongoing inflammation ,125.The presence of non-ischemic LGE is a marker of possible arrhythmic risk per se. Recently, it has been suggested that LGE amount, but also pattern and localization  may carry higher arrhythmic risk . MoreoveLeft ventricular non-compaction (LVNC) is characterized by prominent myocardial trabeculations and a thin compacted myocardial layer. The proposed diagnostic criteria rely on the evidence of a high non-compacted to compacted ratio on echocardiography or on CMR ,132,133.On the other hand, high preload conditions including physiological adaptation to pregnancy or intensive exercise are also associated with increased LV trabeculation. Indeed, almost 20% of asymptomatic athletes can have increased LV trabeculation and up to 8%, in particular those of African or Afro-Caribbean origin, fulfil the criteria for LVNC ,136,137.A complete and multimodal approach is essential for the diagnosis of LVNC, especially in athletes. In suspected cases of LVNC, CMR should be performed to confirm hyper-trabeculation, to better assess LV kinetics and function and to detect areas of LGE that are suggestive for cardiomyopathy  Figure . ImportaLGE presence may be seen in LVNC, but the sensitivity is not particularly high . HoweverRecently, mapping studies on LVNC have shown that higher ECV values correlate with worsened outcomes . FT-CMR The estimated prevalence of anomalies of the coronary artery origin (ACAO) in the general population is low; nevertheless, it is a well-recognized substrate of SCD in athletes . Higher The use of the novel CMR conditional ergometer allows an even more physiological approach to detect hemodynamic relevance of anomalous coronary arteries by analyzing regional wall motion during physical exercise. This approach is promising and could be superior to stress echocardiography , however its routine clinical use is not yet fully established. Cardiac motion artefacts at high heart rate as well as breathing artefacts and chest motion artefacts limits image quality, but the improvement of image acquisition techniques  will likely extend the possibilities in this field  159]..159].Finally, evaluation of LGE can offer a demonstration of a previous myocardial ischemia and an aid for risk stratification.As demonstrated in the previous sections a wide variety of CMR sequences offer a detailed description of the heart making it an imaging modality of increasing popularity. However, CMR is also prone to certain technical difficulties and pitfalls that may entail important limitations. The detailed description of CMR artefacts is beyond the scope of this review, and here we refer to source documents addressing these issues . It shouUntested or low interobserver variability can cause issues during post-processing as well as different contouring methods. It has been long debated if we should include papillary muscles into the compact myocardium or use a simplified contouring technique excluding the papillary muscles and trabeculae . Apart fCMR plays a key role in the identification of cardiovascular disease in athletes, and its application is growing fast. In order to create equal opportunities for diagnosis among athletes, we must tackle several issues. Most evidence on athletes come from the male population. Therefore, studies are needed on female athletes’ heart, as it is known that the pattern of remodeling follows relevant sex differences. Moreover, the validation of normal ranges for physiological heart adaptation among all racial groups using CMR is key to promoting unbiased diagnosis making.Research should focus on establishing robust normal ranges and cut-off values with regards to less well represented groups in the literature. Clear descriptions of standard operating protocols on how metrics were derived should be prioritized and well documented. To enable the clarification of pathological alteration in lower throughput centers, these normal ranges should be openly available to all.The increasing use of CMR in the pre-participation screening of competitive athletes is partially limited by the higher cost and lower availability in comparison to echocardiography, as well as the impact of possible false-positive results such as the evidence of a focal area of LGE of uncertain meaning.Myocardial scarring has been included in the novel European Society of Cardiology guidelines  as a cri


Heart failure affects ∼64 million people worldwide, resulting in high morbidity, mortality and societal cost. Current treatment strategies are primarily geared at slowing the progression to an advanced disease state, but do not reverse or cure heart failure. A more comprehensive understanding of the underlying biology and development of preclinical models of this heterogeneous group of disorders will improve diagnosis and treatment. Here, we summarise recent preclinical and translational research in this area published in Disease Models & Mechanisms. We also discuss how our Journal is propelling this field forward by launching a Special Issue and ongoing subject collection, ‘Moving Heart Failure to Heart Success: Mechanisms, Regeneration & Therapy’. Heart failure is characterised by weakening or stiffening of this vital organ, resulting in impediment of its function. Heart failure is most often associated with ischaemic heart disease or high blood pressure, but also arises due to congenital heart disease, cardiomyopathy, arrhythmias, heart valve abnormalities and inflammatory disorders. Globally, heart failure affects ∼64 million people . VariousIn recent years, Disease Models & Mechanisms (DMM) has published a growing number of articles that propel preclinical and translational research in heart failure forward. Our archive of Open Access primary Research and Resource articles, as well as comprehensive Reviews, showcases the important progress this field has made in developing tools and preclinical models to improve our understanding of the mechanisms of heart failure and develop new therapeutic strategies.in vitro single-cell platforms and 3D cardiac organoids to small and large animals and even organ-level computational models, are instrumental in driving this progress. For example, a recent Resource article describes a robust platform for high-quality recordings of in vivo adult zebrafish electrocardiograms that will improve our ability to investigate mechanisms and therapies for a wide spectrum of human cardiac disorders in zebrafish models  maturation , a disease characterised by progressive muscle wasting that is featured in our subject collection ‘ Models’ . Animal  Models’ . However Models’ , rat , Milena Bellin  and Ravi Karra . The Special Issue will focus on the mechanisms and therapies for congenital heart disease and heart failure. Although heart failure is frequently related to cardiac ischaemia or high blood pressure, which have extensive coverage, this Special Issue will focus on heart failure associated with congenital heart disease, cardiomyopathy, arrhythmias, heart valve abnormalities and inflammatory disorders. We also welcome advances in the development of new model systems, resources, datasets and technologies for studying heart pathophysiology, repair and regeneration. We invite you to submit your breakthrough research to this Special Issue by Monday 1 August 2022.To continue our commitment to this important field of biomedical research, we are launching a Special Issue and ongoing subject collection, Read & Publish agreements with institutional libraries and library consortia, allowing corresponding authors at these institutes to publish an uncapped number of Open Access Research articles without paying an article processing charge. After the publication of this Special Issue in spring 2023, we will launch an ongoing collection to continue our commitment to this area of research.Your submissions will be handled by expert academic Editors and will receive high visibility and impact. We allow format-free submission, and our continuous publication model means that DMM will publish your article as soon as it is accepted. DMM is an Open Access journal, and we are included in a growing number of Cardiovascular research is an expansive and evolving area. With limitations in existing drug efficacy and transplantation availability, there is an urgent need to explore more innovative therapeutic options. In our upcoming Special Issue , we aim