This report provides new evidence that resting measures of cardiac structure and function in elite winter sport professionals can identify sport specific remodeling of the left heart, against the background of training schedule and training frequency.Twelve world elite Biathlon (Bia), ten Nordic Cross Country (NCC) and ten ski-mountaineering (Ski-Mo) athletes were evaluated for pronounced echocardiographic physiological cardiac remodeling as a primary aim of our descriptive preliminary report. In this context, sports-related cardiac remodeling was analyzed by performing two-dimensional echocardiography including speckle tracking analysis as left ventricular global longitudinal strain (LV-GLS). A multicenter retrospective analysis of echocardiographic data was performed in 32 elite world winter sports athletes, which were obtained between 2020 and 2021 during the annual medical examination. The matched data of the elite world winter sports athletes  were compared for different echocardiographic parameters. Significant differences could be revealed for left ventricular systolic function (LV-EF,  Ski mountaineering (Ski-Mo) is one of the most endurant sports imaginable, as it involves the whole body, mostly performed at altitude involving uphill locomotion, representing a high-energy-demanding elite winter sport ,3,4,5,6.The term athlete’s heart describes different changes and adaptions, namely structural, functional, physiological, and electro-physiological, due to sport-specific cardiac remodeling . DiffereIn our preliminary report of elite winter sport athletes, we want to focus on the exercise-induced cardiac remodeling of the athlete’s heart by two-dimensional echocardiography including longitudinal peak strain examination . This meTherefore, the aim of the present descriptive preliminary report is to detect functional and morphological cardiac remodeling in extreme winter sports athlete’s heart.The local ethics committee of the University of Nurnberg-Erlangen approved the study protocol (17_21 B). The study was conducted in conformity with Good Clinical Practice and the declaration of Helsinki . Before Thirty-two young elite winter sport professionals, all active members of the German National Team, participating in world cups and world championships, were examined during the season 2020/2021. During the severe COVID-19 pandemic situation, no participant was infected or had to be excluded from the analysis due to post-COVID-19 infection syndromes. All participants underwent a sports medicine check-up in their sport medicine performance center—Institute for Applied Exercise Science, University Leipzig and Interdisciplinary Center of Sportsmedicine, Klinikum Bamberg in the preseason preparation summer time. All participants were professional athletes with a total amount of 20–25 training hours per week in high-volume training time and 5–10 training hours in recreation time. Neither arrhythmias nor a known cardiac familiar defect have been detected during their sports career. As part of the sports medicine checkup, we performed an echocardiographic functional and morphological assessment using a commercially available echocardiographic system Phillips EPIQ 7 device with an X5-1 aMatrix-array transducer , following a standard protocol . The imaBased on the two-dimensional echocardiographic measurements, the left ventricular mass index (LV Mass index) was calculated with a validated method , the relFor assessment of the LV diastolic function, we measured the pulse-wave Doppler in the apical four-chamber view referring to the peak early filling (E wave) and late diastolic filling (A wave) velocities. A tissue Doppler imaging of the lateral mitral anulus in the apical four chamber view was performed (peak early velocity E′) ,37.Furthermore, a LV speckle tracking analysis of the athlete’s heart was recorded, focusing on the LV-GLS pattern by two-dimensional strain in the apical views. We focused on the analysis of the LV and did not perform RV strain analysis.Each of the participants was evaluated for the prevalence of right and left heart valve regurgitation as part of the standard echocardiographic assessment.p < 0.05). Afterwards, a gender-specific analysis for the interesting parameters was utilized equally.Data were analyzed with Graph Pad Prism 8.2.1(279)  and Minitap statistic program . Our sample size was not normally distributed; therefore, we evaluated our numerical data group comparisons for ten Ski-Mo athletes, ten NCC athletes, and twelve elite Bia athletes using the analysis of variance testing (ANOVA) and nonparametric testing with post-hoc testing  for untrained sedentary controls .All athletes showed a normal systolic LV-EF, but the Bia athletes showed a significantly higher normal systolic LV-EF compared to Ski-Mo and NCC athletes (results shown in 2) was significantly enlarged in our NCC and Bia athletes in comparison to Ski-Mo athletes , the left ventricular posterior wall diameter (LVPWd) and RWT. NCC and Bia athletes showed thicker wall diameters than the Ski-Mo athletes, as shown in the After proving sport-specific LA cardiac remodeling, the comparison of E/A and E/E′ ratio as criteria for LV diastolic function, revealed significant differences between NCC athletes and Bia athletes with respect to E/A, but not with respect to E/E′. The gender-specific subgroup analysis could not reach significant differences , for the end-diastolic volume (LV EDVedd), the right heart dimensions as right atrial end-systolic diameter (RA endsyst) and right ventricular end-diastolic size (RV edd) as well as the TAPSE of RV in our three different elite winter sport disciplines. The sex-specific analysis across the three cohorts did not reach significant differences for the mentioned five parameters either, i.e., LVedd, LV EDVedd, RA endsyst, RV edd and TAPSE  position statement paper 2020 as generally sedentary control measurements, as presented in In the present descriptive preliminary report, the morphological and functional cardiac remodeling due to high-performance competition and training volume in elite winter sports athletes was investigated for the first time. The investigated winter sports in this study represent the most endurant competitive sports as they involve the whole body, are often performed at altitude and are associated with high and intense energy demands ,2,3,7,8.The characteristics of the athlete’s heart have been investigated mostly in the LV as described by Utomi et al. . The anaOf the three disciplines, Ski-Mo represents the sport with the highest endurance component during training . Most ofThe LVedd and LV EDVedd did not reveal significant differences in our investigated groups of elite athletes, which showed a tendency for bradycardia in general, what has to be taken into consideration by evaluating this parameter. Another morphological remodeling key aspect is the induced LV hypertrophy in older athletes. Therefore, we evaluated in our cohorts the LV mass index, whereby Ski-Mo athletes showed significant lower values compared to NCC and Bia athletes as demonstrated in These results must be handled carefully since the results may be due to inter-group differences in age, height and weight, BMI and BSA. Interindividual differences determined the group of Ski-Mo athletes as the physically smallest and youngest athletes, which might contribute to the obtained differences. Besides the physical status, the differences up to training schedules have to be taken into consideration. All participants in this study were professional athletes with a total amount of 20–25 training hours per week, but the Ski-Mo athletes were the youngest athlete category, with the fewest life time training hours and less years of participation as an elite athlete. The main training focus in Ski-Mo athletes is set on ET sessions, whereas ST sessions represent an essential part in Bia and NCC athletes’ training schedule. These circumstances have to be taken into consideration while investigating the progress of exercise-induced cardiac remodeling. Generally, a greater wall thickness of the LV is observed in athletes focusing on ST, i.e., static aspects . In our Sports-specific remodeling consisted of left heart dimension adaption , in a coIn this controversy of training-related cardiac adaption and functional remodeling versus a beginning balanced cardiomyopathy in male endurance athletes, new insights were provided by Utomi et al. . The aut2max and LA passive emptying fraction, which might contribute to improved exercise capacity in athletes and improved cardiac output during exercise [In our study, LA remodeling was observed especially in NCC and Bia athletes. Our evaluated parameter, LAVI, revealed in our small number of participants significantly different results, which implies significantly higher values for the NCC and Bia athletes compared to Ski-Mo athletes. These athletes are represented mainly as a homogenously young and physically small group of male and women athletes. Therefore, our results have to handled with care and can only serve as a description of structural cardiac remodeling of world professional winter sport athletes. Nevertheless, LA remodeling has been described as a typical characteristic in endurance athletes . Howeverexercise . On the exercise .The functional remodeling of the LV can be evaluated using the peak early to late diastolic filling ration (E/A ratio) and tissue doppler analysis (E/E′ratio). Higher values are observed in athletes in comparison to non-athletes . We founNevertheless, discussing the specific cardiac remodeling of the winter sport elite athlete’s heart, it has to be stated clearly that the prognostic value of reported echocardiographic assessment is limited and does not provide sensitive results for at least two frequent conditions of sudden cardiac death in athlete’s heart. Firstly, coronary artery anomalies and secondly the non-compaction cardiomyopathy of the LV cannot be sensitively detected or ruled out by two-dimensional echocardiographic assessment. Therefore, further cardiac imaging techniques, such as computer tomography or cardiac MRI should be considered ,53,54. IEchocardiographic two-dimensional speckle tracking is a modern method for identifying subtle differences in the adaption of LV strain cardiac pattern or twist mechanism of the LV in athletes . The disThe right side of the heart in athletes has also received some interest in the past as well as in the current scientific view. In a systematic review in athletes, Ascenzi et al.  detectedOur study has several limitations as mentioned above in the discussion. First of all, the number of professional winter sport athletes is relatively small which is due to the fact that we only investigated high-level athletes from the German national teams competing at world-class events. Secondly, Ski-Mo athletes were the youngest athlete category, implying fewer lifetime training hours and showed a smaller physical constitution than NCC and Bia athletes—these circumstances have to be taken into consideration, while evaluating sport-specific cardiac remodeling and we agree that our paper should be likely regarded as an interesting descriptive preliminary report. Furthermore, the echocardiographic analyses of the participating athletes were performed in a multicenter study design, so that an interobserver variability with respect to measurement acquirement must be considered on the one hand. On the other hand, the mixture of young and experienced athletes especially in the NCC and Bia athlete cohort entails an interindividual variability in relation to anatomical habitus, lifetime training hours and training schedule variability, which might contribute to a certain standard deviation in our measurements. Thirdly, the multicenter measurement was performed in the preseason preparation time in summer. This condition associated with individual training schedules might contribute to individual athlete’s heart volume change and result in this difference. Our functional left ventricular analysis has been focused on the LV-GLS and not on the circumferential strain analysis of the LV. No specific strain analysis has been performed in the RV, which is an important limitation of this study and might be performed in further investigations.This is the first study to present data of world class winter sports athletes and morphological and functional remodeling of the left heart.Our results have to be handled with care due to the mentioned limitations and serve as a preliminary report. Therefore, our results analysis—in general as well as in the gender-specific subgroup—can identify physiological differences in functional and morphological cardiac remodeling, especially due to LV-EF and LV mass index, LA remodeling as measured by LAVI, and differences in the speckle tracking analysis, focusing the LV-GLS. Nevertheless, the individual morphological and secondary functional adaption of the athlete’s heart have to be interpreted carefully due to the different types of sports and lifetime training hours. From this aspect, future studies should consider a greater number of participating athletes to verify the impact on sport-specific cardiac remodeling and to further strengthen the evidence base.


Acute appendicitis (AA) might be amenable to conservative antibiotic treatment, whereas a perforated appendix (PA) necessitates surgery. We investigated the value of clinical–laboratory markers in distinguishing AA from a PA. n = 237) vs. PA (n = 69)), treated at our institution between January 2014 and December 2017.  Retrospectively obtained preoperative parameters for 306 consecutive patients (<18 years) with histologically confirmed appendicitis  level, and CRP-to-lymphocyte ratio (CLR). Upon discrimination analysis, CLR and CRP displayed the highest accuracy in differentiating a PA from AA. Regression analysis identified levels of CRP, sodium, and the Tzanakis score as independent predictors for a PA.  Levels of CLR, CRP, sodium, and Tzanakis score might support decision-making regarding treatment options for pediatric appendicitis. Appendicitis is a common general-surgical emergency. A lifetime risk of 8.6% in males and 6.7% in females, with a peak incidence during the second decade of life, has been documented for appendicitis , 2.The diagnosis of appendicitis in children is challenging because of the following: (i) often atypical presentation, (ii) misleading symptomatology, (iii) preverbal status of children aged <2 years, and (iv) increased susceptibility to infectious states  that mimic appendicitis  . The preAdvances in imaging and increased use of ultrasound (US) in children (which carries a sensitivity of 44–94% and specificity of 47–95%) have led to a decline in the prevalence of unnecessary appendectomies, but the prevalence of a PA has remained relatively unaltered . Those dSeveral scoring systems have been used in clinical practice –11. ReceRecently, hyponatremia has been reported as a very sensitive marker of advanced acute appendicitis in children with sensitivity and specificity of 94.7% and 88.5%, respectively .At our institution, surgery is undertaken on all children with appendicitis regardless of the index of suspicion for a PA. However, according to recent research, a non-PA might undergo spontaneous resolution and seems to be more receptive to conservative antibiotic treatment alone, whereas other types of appendicitis presentation with a PA before hospital admission necessitates surgery –16. In tThe study protocol was approved (19-6741-BR) by the Ethics Committee of the Ruhr-University of Bochum (Germany).th Revision, German Modification) code for appendicitis (K35.) and the OPS (Operation and Procedure Coding System) code for appendectomy (5-470) during study period 01/2014–12/2017. Exclusion criteria were age above 17 years, nonavailability of laboratory (n =3) or histopathological data, and coassociated confounding factors as appendicoliths, infections , or hematologic disorders  and PA (n = 69). As proposed by Saint Peter and colleagues, a “perforation” was defined as a hole in the appendix confirmed by histopathology [Based on the histopathology classification, data were dichotomized into AA , lymphocytes (109/L), CRP (mg/dL), CRP level-to-lymphocyte-count ratio , and sodium (mmol/L). The Tzanakis scoring system was utilized for improving the predictive value of single factors in the diagnosis of appendicitis [9/L) with a cutoff ≥8 out of a maximum of 15 points being considered predictive of AA.Hematology parameters were obtained upon hospital admission: WBC 10/L, lymphThe sampling and analyses of data were done using Excel™ . Statistical analyses were undertaken with OriginPro™ 2021b  and SPSS 27  for binary regression analysis.t-test for parametric data and the Mann–Whitney U-test for nonparametric data. The area under the receiver operating characteristic (ROC) curve of relevant parameters compared with that in their control group was calculated, and the sensitivity at 95% specificity is given. Analyses of ROC curves enabled evaluation of the optimal cutoff for variables that could be used to predict PA, and the Youden Index was used [p ≤ 0.05 was considered significant.Data are the arithmetic mean ± SD or median and quartiles (Q1–Q3) if a nonnormal distribution was observed. Categorical variables are presented as frequencies and percentages. A normal distribution of numeric variables was confirmed by the Kolmogorov–Smirnov normality test at a significance level of 0.05. Comparisons of dichotomic variables were carried out using the Student's was used . Sensitiwas used , variabln = 132; 43.1%). Data was dichotomized into AA  and PA (n = 69). The overall prevalence of a PA was 22.5% . Compared with the AA group, a PA was associated with a younger age (p < 0.001) (p < 0.001) (p < 0.001). In the PA group, the CRP level (p < 0.001) (p < 0.001) (p < 0.001) (p = 0.83), compared with those in the AA group. The sodium level was reduced in the PA group (p < 0.001) (p < 0.001 for both). The vast majority of cases  were treated by conventional 3-port laparoscopic appendectomy; conversion from laparoscopy to laparotomy was necessary in 13 cases, and 5 cases had primary laparotomy.Basic clinical, laboratory, and procedural characteristics are given in < 0.001) , an incr< 0.001) , and a h< 0.001) , WBC cou< 0.001)  and CLR < 0.001)  upon hos< 0.001) . ProceduROC analyses for differentiation of AA from a PA  revealedp = 0.050) and CRP  and the Tzanakis score  were retained in the final model of independently associated variables with PA. However, when CRP was replaced by CLR in the regression model, the latter was the only variable independently associated with PA .The independent regression parameters were identified by AUC values ≥0.7 from ROC analysis and were considered eligible for binary logistic regression analysis (Enter method) if the variance inflation factor  was within the threshold of 2.5, as proposed by Midi and colleagues . Due to We wished to evaluate the value of basic clinical–laboratory parameters in differentiating a PA from AA in a pediatric cohort. An increased CRP level and Tzanakis score, together with hyponatremia, were of independent predictive value for a PA. Moreover, in this context, the value of CLR might be equal to, or greater than, that of CRP. This information could foster decision-making towards the treatment of AA and PA cases.The present study had several limitations. First, it was retrospective. Second, it was from a single center. Third, the study cohort was relatively small. Fourth, longitudinal laboratory data were lacking, so conclusions on possible dynamic variations in the investigated parameters could not be drawn. Fifth, the validity of data on body temperature may have been compromised by the preceding use of antipyretic medication because documentation of this issue was not part of our study protocol.We observed reduced levels of sodium in the PA group , and simIn our series, the CRP level was more sensitive than the WBC count for detecting a PA . AccordiIn search of a more sensitive marker that reflects systemic inflammation and the immunological response, the CLR was applied Tables . To our inter alia clinical progression of appendiceal inflammation. Although the Tzanakis score displayed only moderate discriminatory ability  treatment in AA or surgery to treat a PA.


Leadless cardiac pacemakers such as the Micra™ transcatheter leadless pacing system  are an alternative to traditional transvenous pacemakers. Implantation of leadless pacemakers, albeit safe, may be associated with complications, including cardiac tamponade; high capture thresholds; and, rarely, ventricular arrhythmias. We report a case of ventricular fibrillation arrest following the implantation of a Micra™ leadless pacemaker. This has been achieved following advances in PM battery, component design, and chemistry that have led to leadless pacemakers (LPs) small enough to be placed directly in the heart, which may lead to a reduction in complications associated with conventional transvenous leads and pockets.4Leadless cardiac pacemakers (PMs) are an alternative to conventional transvenous PMs designed to avoid the need for transvenous leads and pockets.5Leadless cardiac PMs are completely self-contained, encapsulated in a small unit, and are affixed by nitinol tines to the myocardium in the right ventricle through a minimally invasive transcatheter approach via the femoral vein. Reynolds et al. and Reddy et al. reported two multicenter studies which found LPs to be a promising alternative to older transvenous systems.6 However, the procedure may be associated with complications, which include traumatic cardiac injury with cardiac perforation and pericardial effusion; high capture thresholds; and, rarely, ventricular arrhythmias.8 While some of these complications such as traumatic cardiac injury may be attributed to the learning curve of operators handling this novel technology, other complications such as arrhythmia may be secondary to the implant position of the device.9The Micra™ transcatheter leadless pacing system , an example of an LP, has demonstrated high procedural success rates.Few cases of ventricular arrhythmias due to Micra™ implantation have been reported in the literature. We wish to add to the literature by presenting a case of ventricular fibrillation (VF) arrest temporally related to Micra™ implantation.Staphylococcus aureus bacteremia. The source of her bacteremia was thought to be her AV graft, which was excised for source control. Her initial electrocardiogram (ECG) showed sinus rhythm , but her hospital course was complicated by the development of complete heart block with a narrow junctional escape rhythm and paroxysmal atrial fibrillation. Further workup with a transesophageal echocardiogram demonstrated a small mobile echo density measuring 4 × 5 mm attached to the coumadin ridge. She was placed on prophylactic and not therapeutic anticoagulation due to a high bleeding risk. Cardiac computed tomography ruled out the involvement of the aortic root, ie, aortic root abscess or pseudoaneurysm. No other reversible causes of her complete heart block could be identified. Subsequently, a transvenous pacing wire was successfully placed within the right ventricle.A 62-year-old woman with a history of hypertension, type 2 diabetes, and end-stage renal disease was admitted to the hospital with bleeding from her arteriovenous (AV) graft and was found to have methicillin-resistant Given her diagnosis of infective endocarditis and need for a prolonged course of antibiotics, the decision was made to proceed with the implantation of a permanent pacing system. The patient decided to undergo Micra™ transcatheter LP implantation, due to her recent history of extraction of her potentially infected left upper-extremity AV graft and previously documented right subclavian vein occlusion. Subsequently, the patient underwent Micra™ implantation through the right femoral vein. After the device was deployed, the pull-and-hold test was performed to ensure adequate fixation. The postfixation electrical testing of the device demonstrated an R-wave sensing value of 6.5 mV, an impedance of 550 Ω, and a pacing threshold of 1.3 V at 0.24 ms. The latter improved to less than 1 V at 0.24 ms before the end of the case. Hence, the decision was made to cut the tethering suture and release the Micra™ device. Postprocedure, the patient remained stable and was transferred to the medical floor.Figure 2. She did not have hyperkalemia and was not on any concomitant proarrhythmogenic or QT-prolonging medications. She received seven shocks and eight ampules of epinephrine in addition to intravenous amiodarone and lidocaine boluses. Return of spontaneous circulation was subsequently achieved, and she was transferred to the cardiovascular intensive care unit.Approximately five hours following Micra™ insertion, she developed VF cardiac arrest. The telemetry strip for the event is shown in Figure 3. However, the chest X-ray was obtained after the VF arrest and she was not in respiratory distress or hypoxia prior to the arrest. Her serum electrolytes, including potassium, and blood counts were within the normal limits and unchanged from admission. Given the lack of a clear explanation for her VF arrest and given the temporal association with the Micra™ device implantation, her VF was presumed to be secondary to myocardial irritation from the Micra™ device. Unfortunately, she developed worsening shock with increasing vasopressor requirements and was later transitioned to comfort care following a family discussion and subsequently expired within 18 hours of the original procedure.In the cardiovascular intensive care unit, she was started on norepinephrine and vasopressin for hemodynamic support. Her Micra™ interrogation showed normal device function with stable impedance, sensing, and slightly higher pacing threshold values. The latter, however, remained below the programmed pacing output of the device. A post–cardiac arrest ECG showed a ventricular-paced rhythm with occasional premature ventricular complexes (PVCs). Transthoracic echocardiography did not show any evidence of pericardial effusion, and her chest X-ray showed stable device positioning from implantation and diffuse infiltrates as seen in 11 Our case sheds further light on this complication by adding to the existing literature.This case demonstrates potential Micra™ LP–induced VF arrest in our patient. Despite extensive workup, the etiology of VF arrest in our patient remained unclear. Although local myocardial irritation from the implantation of the Micra™ device as a trigger of VF is possible, it is unlikely given the difference in the morphology of the PVC that initiated VF versus paced QRS complexes. Other case reports of ventricular arrhythmias following LP device implantation have also been reported.12 In a retrospective Swiss study evaluating the safety and efficacy of Micra™ implantation in 92 patients, one patient developed unstable ventricular tachycardia (VT) during implantation; two months later, he was hospitalized again with intractable VT requiring ablation. During the ablation, the VT was mapped to an origin site close to the insertion site of the device.7 In contrast, early results from the Micra™ Postapproval Registry, an ongoing global, prospective, observational registry evaluating the safety and efficacy of Micra™ implantation, showed that none of the 1,801 patients who underwent the procedure developed ventricular arrhythmias.13Current studies show the Micra™ LP to have an acceptable safety profile; however, reports of perioperative and postoperative ventricular arrhythmias have been described. Ritter et al. originally described the early performance of Micra™ and its safety profile in a prospective multisite study; among the cohort of 140 patients who underwent Micra™ implantation, three individuals developed ventricular arrhythmias that were not associated with death, reoperation, or hospitalization.12 Amin et al. reported a case of PVC-induced polymorphic VT resulting in episodes of near-syncope and dizziness in a 74-year-old patient one day after Micra™ LP implantation. The PVCs were hypothesized to be secondary to local irritation of the right ventricular myocardium at the site of Micra™ implantation. Similarly, in the Swiss study, the unstable VT was attributed to a proarrhythmic effect of the nitinol fixation tines.7 Another report describing polymorphic VT post–Micra™ implantation hypothesized that local inflammation via cytokine-mediated cardiac remodeling likely contributed to VT in their case.14 In contrast, Da Costa et al. described a case of cardiac arrest within hours following Micra™ implantation; the ventricular tachyarrhythmia occurred during ventricular pacing and not spontaneously, and pacing-related induction of VF was considered a possibility.11 Coronary ischemia may be a possible etiologic factor; however, our patient had no history of coronary artery disease.Different mechanisms for the development of ventricular arrhythmias after Micra™ implantation have been proposed.9 A report by Olsen et al. describes cardiac arrest due to VF post–Micra™ implantation that resolved only after the removal of the LP.10 Similarly, the case of recurrent hemodynamically unstable VT from the Swiss study demonstrated that, despite management with amiodarone, β-blockers, verapamil, lidocaine, and external defibrillation, the arrhythmia ultimately resolved after surgical explantation of the Micra™ device.7 In contrast to these three reports, the case of polymorphic VT after Micra™ implantation was managed with intravenous steroids and overdrive pacing, resulting in the resolution of repolarization abnormalities.14Importantly, while some of these cases were managed conservatively, others have shown that retrieval of the LP results in the resolution of the arrhythmias. In the case described by Amin et al., the patient subsequently underwent a second Micra™ implantation with retrieval of the prior device to alleviate symptoms.After Micra™ LP implantation, patients can abruptly develop ventricular arrhythmias, leading to significant morbidity and mortality rates. Although the literature is currently limited to case reports following the initial device performance data, we believe that further, larger studies will help to illustrate this relationship. These adverse events highlight the importance of close monitoring of patients in the postoperative period to minimize complications with timely intervention. We propose that patients undergoing Micra™ implantation should be closely monitored for ventricular arrhythmias in the early postoperative period.LPs require direct implantation into the myocardium and, though promising, may be associated with life-threatening proarrhythmic effects in some patients. Patients with such devices may benefit from close postprocedural monitoring for arrhythmias and other complications. Larger studies are needed to investigate the possible risk factors for arrhythmias in patients with leadless pacing devices and optimize postprocedural management.


Megaptera novaeangliae) are indicative of cumulative cultural evolution. Using nine years of song data recorded from the New Caledonian humpback whale population, we quantified song evolution and complexity, and formally evaluated this process in light of criteria for cumulative cultural evolution. Song accumulates changes shown by an increase in complexity, but this process is punctuated by rapid loss of song material. While such changes tentatively satisfy the core criteria for cumulative cultural evolution, this claim hinges on the assumption that novel songs are preferred by females. While parsimonious, until such time as studies can link fitness benefits (reproductive success) to individual singers, any claims that humpback whale song evolution represents a form of cumulative cultural evolution may remain open to interpretation.Culture presents a second inheritance system by which innovations can be transmitted between generations and among individuals. Some vocal behaviours present compelling examples of cultural evolution. Where modifications accumulate over time, such a process can become cumulative cultural evolution. The existence of cumulative cultural evolution in non-human animals is controversial. When physical products of such a process do not exist, modifications may not be clearly visible over time. Here, we investigate whether the constantly evolving songs of humpback whales (This article is part of a discussion meeting issue ‘The emergence of collective knowledge and cumulative culture in animals, humans and machines’. Two major concepts are apparent from song and complexity analyses: the cyclical nature of complexity , it is being fashionable that is ‘attractive’. Demonstrating the ability to identify and rapidly adopt new fashion trends shows superior social learning and cognitive abilities that increase a wearer's cultural fitness. Similarly, rapidly adopting changes to the song (i.e. artefact) might increase the reproductive potential of a male humpback whale. Studies investigating reproductive success of singers at the vanguard of song changes are needed to confirm this hypothesis.The second concept is the constantly changing patterns of the song ,53. Giveimprovement as the improvement of the aesthetic attractiveness of song to females, given the assumption that females should prefer more novel songs, then this criterion would be satisfied as the males are improving their fitness by changing their songs. Such a system seems highly plausible given the observed uptake of novel humpback whale songs within a population [If we interpret the criteria for pulation ,76 in copulation ,70 hypotpulation . Furtherpulation   as opposed to ‘attractive’ to females (i.e. leading to direct or indirect reproductive success) is currently outside the scope of behavioural experiments. This makes teasing apart the cultural process from those of sexual selection difficult. Therefore, the current state of evidence to satisfy the criterion of repeated over time and in multiple populations to generate changes to the song [Finally, there is clear evidence that innovation and social learning are the song ,52,57,80the song ,85; malethe song . During the song . Hybrid the song . As songthe song –92), it the song , and higthe song  where eathe song : functio. 5introduction, transmission and repetition—but it is open to interpretation whether we have meet the criteria for improvement [Here, we have shown that song complexity changes in a quasi-sinusoidal manner mirroring periods of song evolution and rapid revolution over nine years within the New Caledonian humpback whale population. Song accumulates changes shown by an increase in complexity, but this process is punctuated by rapid loss of song material. We have robustly met three of the four core criteria for cumulative cultural evolution—rovement . Until s


The Global Registry of Acute Coronary Events (GRACE) score was developed to evaluate risk in patients with myocardial infarction. However, its performance in type 2 myocardial infarction is uncertain.n = 48 282) and a tertiary care hospital in Sweden (n = 22 589), we calculated the GRACE 2.0 score to estimate death at 1 year. Discrimination was evaluated by the area under the receiver operating curve (AUC), and compared for those with an adjudicated diagnosis of type 1 and type 2 myocardial infarction using DeLong’s test. Type 1 myocardial infarction was diagnosed in 4981 (10%) and 1080 (5%) patients in Scotland and Sweden, respectively. At 1 year, 720 (15%) and 112 (10%) patients died with an AUC for the GRACE 2.0 score of 0.83 [95% confidence interval (CI) 0.82–0.85] and 0.85 (95% CI 0.81–0.89). Type 2 myocardial infarction occurred in 1121 (2%) and 247 (1%) patients in Scotland and Sweden, respectively, with 258 (23%) and 57 (23%) deaths at 1 year. The AUC was 0.73 (95% CI 0.70–0.77) and 0.73 (95% CI 0.66–0.81) in type 2 myocardial infarction, which was lower than for type 1 myocardial infarction in both cohorts .In two cohorts of consecutive patients with suspected acute coronary syndrome from 10 hospitals in Scotland (The GRACE 2.0 score provided good discrimination for all-cause death at 1 year in patients with type 1 myocardial infarction, and moderate discrimination for those with type 2 myocardial infarction.ClinicalTrials.gov number, NCT01852123. This assay has an inter-assay coefficient of variation of <10% at 4.7 ng/L and a 99th centile of 16 ng/L in women and 34 ng/L in men., 2. The obtained data, together with laboratory data, were sent to the Swedish National Board of Health and Welfare who linked information on comorbidities and outcomes, use of medication, and dates and causes of death from the National Patient Register, the Prescribed Drug Register, and the Cause-of-Death register, respectively. The Patient Register has nationwide coverage on diagnoses at discharge and surgical procedures coded according to the International Classification of Disease. Details of study approvals are contained in the The study population from the Karolinska University Hospital in Stockholm was derived from an observational cohort study of all patients >25 years old with a visit to the Emergency Department with chest pain and at least one hs-cTn measurement from January 2011 to October 2014.All diagnoses were adjudicated in accordance with the Fourth Universal Definition of Myocardial Infarction.The primary outcome was all-cause death at 1 year, and the secondary outcome was all-cause death or type 1 myocardial infarction at 1 year. All in-hospital and community deaths are recorded on the National General Register of Scotland, and the Swedish Patient Register. Subsequent myocardial infarction events were identified through the electronic patient record in Scotland with adjudication as for the index diagnosis, and using ICD-10 coding (I21 and I22) from the Swedish Patient Register in the Swedish cohort.2, Kruskal–Wallis, or one-way analysis of variance tests as appropriate. We determined the GRACE 2.0 score for all-cause death, and for all-cause death or type 1 myocardial infarction at 1 year. This score includes age, heart rate, systolic blood pressure, creatinine as continuous variables, with categorical variables for Killip class, cardiac arrest at admission, ST-segment deviation, and elevated cardiac biomarkers (defined here as any hs-cTn concentration above the 99th centile). Where data were missing within the Scottish cohort, this was assumed to be at random, and we applied multiple imputation using chained equations with five imputations of the dataset. For imputation, we applied Bayesian linear regression models for continuous data , multinomial logistic regression for ordinal data (Killip class) and logistic regression for binary data (e.g. cardiac arrest status). We assessed overall GRACE 2.0 model discrimination by determining the area under the receiver operating curve (AUC) and compared performance in patients with type 1 and type 2 myocardial infarction using the DeLong method. We assessed model calibration both graphically, and by using the Hosmer–Lemeshow goodness of fit test. In addition, we assessed GRACE performance by evaluating previously defined categories of mortality risk  using the Kaplan–Meier method. We explored the impact of multiple imputation by performing a sensitivity analysis in which we evaluated the complete dataset only. These results were similar to the primary analysis and are presented in the Table S1. In post hoc analyses, we also determined performance of the GRACE 2.0 score for in-hospital death and of hs-cTn alone to predict all-cause death at 1 year. All analyses were performed in R (Version 3.5.1) and the code required to calculate the GRACE 2.0 score is available in S1.Baseline characteristics were summarized for each cohort and in groups by according to adjudicated diagnosis. Group-wise comparisons were performed using χThe Scottish cohort consisted of 48 282 consecutive patients  with suspected acute coronary syndrome of whom 10 360 (21%) had hs-cTnI concentrations above the 99th centile. It was possible to adjudicate the diagnosis in 88% (9115/10 360) of patients. The final diagnosis was type 1 myocardial infarction in 55% (4981/9115), type 2 myocardial infarction in 12% (1121/9115), and acute or chronic myocardial injury in 18% (1676/9115) and 14% (1287/9115), respectively. The remainder of patients had type 4a (9/9115) or 4b (41/9115) myocardial infarction.The Swedish cohort consisted of 22 589 consecutive patients with suspected acute coronary syndrome of whom 3853 (17%) patients had hs-cTnT concentrations above the 99th centile. The final diagnosis was type 1 myocardial infarction in 28% (1080/3853) of patients, and type 2 myocardial infarction in 6% (247/3853), with acute or chronic myocardial injury in 30% (1144/3853) and 35% (1347/3853), respectively.Table 1). Patients with type 2 myocardial infarction were less likely to be offered coronary angiography, revascularization or secondary prevention than those with type 1 myocardial infarction (Table 2). There were differences in the covariates which influence the GRACE 2.0 score between groups, with higher heart rates (101 vs. 77 b.p.m.), lower systolic blood pressures (130 vs. 141 mmHg) and a higher proportion of patients with increased Killip class observed in those with type 2 myocardial infarction (Table 3).Compared to patients with a diagnosis of type 1 myocardial infarction, those with type 2 myocardial infarction were older (74 ± 14 vs. 68 ± 14 years), more likely to be women (55% vs. 40%), and more likely to have a history of cardiovascular disease. Similar differences were apparent in both cohorts (Table 3) and had good discriminative ability with an AUC of 0.83 [95% confidence interval (CI) 0.82–0.85] and 0.85 (95% CI 0.81–0.89), respectively .We obtained follow-up in 100% of participants for primary and secondary outcomes at 1 year. In patients with type 1 myocardial infarction, 15% (720/4981) and 10% (112/1080) died from any cause at 1 year in the Scottish and Swedish cohorts, respectively. The GRACE 2.0 score was higher in those with type 2 compared to type 1 myocardial infarction across both cohorts .In patients with type 2 myocardial infarction, 23% (258/1121) and 23% (57/247) died from any cause at 1 year in the Scottish and Swedish cohorts, respectively. The GRACE 2.0 score had moderate discriminative ability, with an AUC of 0.73 (95% CI 0.70–0.77) and 0.73 (95% CI 0.66–0.81), respectively, and performed less well than in patients with type 1 myocardial infarction . Calibration plots and the Hosmer–Lemeshow test indicated the GRACE 2.0 score underestimated future all-cause death across all deciles of risk in both type 1 and type 2 myocardial infarction .Similar performance was observed in men and women with type 1 and type 2 myocardial infarction in both cohorts . Baseline demographic information was similar across all categories of risk irrespective of the diagnosis of type 1 and type 2 myocardial infarction (Table S4). In patients with type 2 myocardial infarction in the Scottish cohort at low risk of death, there were fewer new prescription for aspirin (25% vs. 67%), statin (11% vs. 56%), angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (15% vs. 49%) compared to those with type 1 myocardial infarction. Similar patterns were observed in patients at intermediate or high risk of death.In the Scottish cohort, we evaluated conventional GRACE categories of low, intermediate, and high predicted risk of mortality. Observed event rates were higher in patients with type 2 myocardial infarction who had a low or intermediate predicted risk of death  and 16% (173/1080) of patients died or had a myocardial infarction at 1 year in the Scottish and Swedish cohorts, respectively. The AUC for the GRACE 2.0 model incorporating death or future myocardial infarction was 0.76 (95% CI 0.74–0.77) and 0.81 (95% CI 0.77–0.85), respectively.P = 0.007 and P = 0.042 vs. type 1 myocardial infarction). Calibration plots showed the GRACE 2.0 model underestimated future risk in type 1 and type 2 myocardial infarction across both cohorts .In patients with type 2 myocardial infarction, there were 27% (297/1121) and 26% (63/247) deaths or myocardial infarctions at 1 year. Here, the GRACE 2.0 score gave an AUC of 0.70 (95% CI 0.67–0.74) and 0.72 (95% CI 0.65–0.80), respectively . When applied as a continuous variable, both hs-cTnI and hs-cTnT were moderate predictors of all-cause death at 1 year (Table S6).In a We evaluated the performance of the GRACE 2.0 score for the prediction of all-cause death, and all-cause death or myocardial infarction in consecutive patients with type 1 and type 2 myocardial infarction from two independent cohorts across two countries. We observe that the GRACE 2.0 score provides good discrimination for all-cause death in patients with type 1 myocardial infarction diagnosed using hs-cTn assays and for both cardiac troponin I and T. Consistent with the original validation study,The GRACE 2.0 score was derived prior to the publication of the first Universal Definition of Myocardial Infarction,, We recently demonstrated future cardiovascular risk was increased in all patients with myocardial injury and infarction, irrespective of diagnostic classification, despite a vast excess in non-cardiovascular death in patients without type 1 myocardial infarction. Patients with type 2 myocardial infarction were at almost four-fold increased risk of cardiovascular events relative to those without myocardial injury. This risk appears to be highest in those with a history of prior coronary artery disease, suggesting underlying coronary atheroma may at least in part be driving future cardiovascular risk., In this analysis, we demonstrate the GRACE 2.0 score performed well in the prediction of all-cause mortality and future cardiovascular events in patients with type 1 myocardial infarction, but discrimination was lower in those with type 2 myocardial infarction. At the time the GRACE was derived, the diagnosis of myocardial infarction was based on contemporary cardiac biomarkers with a diagnostic threshold at least 10-fold higher than advocated in current guidelines.Some attempts have been made to derive risk stratification tools in patients with type 2 myocardial infarction. The TARRACO risk score was derived in 611 patients with type 2 myocardial infarction and myocardial injury.post hoc analysis, incorporating troponin concentration as a continuous variable could offer improved performance. Whether the inclusion of absolute troponin concentration, comorbidities or additional covariates, such as haemoglobin concentration, could improve model performance requires exploration.Analysis of the calibration of the GRACE 2.0 model in type 1 and type 2 myocardial infarction identified underestimation of risk across all outcomes. This likely reflects differences between the population of consented patients recruited into the GRACE registry, and the consecutive patient cohort evaluated here. There are a number of potentially important comorbidities not included in the GRACE 2.0 score which are common in clinical practice and could influence survival, particularly in those with type 2 myocardial infarction. These include atrial fibrillation, chronic obstructive pulmonary disease, heart failure, malignancy, dementia, and frailty. Furthermore, as suggested in a Given the implementation of hs-cTn assays has been shown to increase recognition and the prevalence of type 2 myocardial infarction, there is an urgent and unmet need to improve risk prediction in these patients. Until bespoke risk prediction tools are available for patients with type 2 myocardial infarction, the GRACE 2.0 allows identification of patients at increased risk of death, both in-hospital and at 1 year. This may be helpful to guide clinicians when reviewing patients with type 2 myocardial infarction and deciding who may benefit from more intensive monitoring or further investigation for underlying coronary disease. We observed lower prescription rates for secondary prevention therapy in patients with type 2 myocardial infarction. This was most evident in those classified by GRACE as low- or intermediate risk, where rates of prescriptions for new antiplatelet or statin therapies in type 2 myocardial infarction were half those of type 1 myocardial infarction, and outcomes were worse. In those classified as high risk, prescription rates and outcomes between patients with type 1 and type 2 myocardial infarction were similar. Whether secondary prevention therapy in patients with type 2 myocardial infarction will improve clinical outcomes requires evaluation in prospective trials.post hoc and is limited by a small number of events. Finally, we acknowledge that the rates of coronary angiography were lower here than in other registries or clinical trials of selected patient populations., We acknowledge some limitations. Firstly, whilst the GRACE 2.0 score was derived and validated across 14 countries, we only evaluate performance in Scotland and Sweden. However, we included consecutive patients across two different healthcare systems using different high-sensitivity troponin assays and found consistent results. The consistency in results was evident despite differences in the original study design and in the selection of patients between the two healthcare sites. Second, whilst we adjudicated all diagnoses according to the latest Fourth Universal Definition of Myocardial Infarction using all available clinical information, we acknowledge that diagnostic misclassification is possible. In the Scottish cohort where there was consensus amongst the adjudication panel that there was insufficient clinical information to make a definitive diagnosis, because of missing admission or discharge letters, we did not attempt to adjudicate the diagnosis. Third, where information on covariates required for calculating the GRACE score was missing this was determined to be at random, and to minimize bias we applied multiple imputation. As data were missing in patients with type 1 and type 2 myocardial infarction in equal proportion, and we observed consistent performance in a sensitivity analysis restricted to the dataset where complete case data were available, we do not think this impacted on the results observed. Fourth, we acknowledge that our analysis of in-hospital events was The GRACE 2.0 score provided good discrimination for all-cause death at 1 year in patients with type 1 myocardial infarction, and moderate discrimination for those with type 2 myocardial infarction. Until specific risk prediction tools are derived and validated, clinicians should consider applying the GRACE 2.0 score to guide prognosis and subsequent management in patients with type 2 myocardial infarction.European Heart Journal online.This trial was funded by a Special Project Grant from the British Heart Foundation (BHF) (SP/12/10/29922) with additional support from a BHF Research Excellence Award (RE/18/5/34216). A.R.C. and N.L.M. are supported by Clinical Research Training Fellowship (FS/16/75/32533) and the Butler Senior Clinical Research Fellowship (FS/16/14/32023) from the BHF. A.R.C. is supported by a Starter Grant for Clinical Lecturers from the Academy of Medical Sciences, which is supported by the Wellcome Trust, the Medical Research Council, the British Heart Foundation, vs. Arthritis, Diabetes UK, and the British Thoracic Society [SGL021/1075]. A.R. holds a research position funded by the regional agreement on medical training and clinical research between Stockholm County Council and Karolinska Institutet (20160644). D.M.K. was supported by a grant from Health Data Research UK which receives its funding from HDR UK Ltd (HDR-5012) funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and the Wellcome Trust. M.J.H. holds research positions funded by the Swedish Heart-Lung Foundation (20170804) and the Stockholm County Council (20170686). Abbott Laboratories provided cardiac troponin assay reagents, calibrators, and controls without charge for the High-STEACS trial. The funders played no role in the design, conduct, data collection, analysis or reporting of the trial.Conflict of interest: A.S.V.S. and A.R.C. have received honoraria from Abbott Diagnostics. N.L.M. has received honoraria from Abbott Diagnostics, Siemens Healthineers, Roche Diagnostics and Singulex, and the University of Edinburgh has received research grants from Abbott Diagnostics and Siemens Healthineers. M.J.H. has received consultancy honoraria from Idorsia.ehaa375_Supplementary_DataClick here for additional data file.


Data on the prognostic value of left ventricular (LV) morphological and functional parameters including LV rotation in patients with dilated cardiomyopathy (DCM) using cardiovascular magnetic resonance (CMR) are currently scarce. In this study, we assessed the prognostic value of global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS) and LV torsion using CMR feature tracking (FT).CMR was performed in 350 DCM patients and 70 healthy subjects across 5 different European CMR Centers. Myocardial strain parameters were retrospectively assessed from conventional balanced steady-state free precession cine images applying FT. A combined primary endpoint  was defined for the assessment of clinical outcome.GLS, GCS, GRS and LV torsion were significantly lower in DCM patients than in healthy subjects . The primary endpoint occurred in 59 (18.7%) patients [median follow-up 4.2 (2.0–5.6) years]. In the univariate analyses all strain parameters showed a significant prognostic value (p < 0.05). In the multivariate model, LV strain parameters, particularly GLS provided an incremental prognostic value compared to established CMR parameters like LV ejection fraction and late gadolinium enhancement. A scoring model including six categorical variables of standard CMR and strain parameters differentiated further risk subgroups.LV strain assessed with CMR FT has a high prognostic value in patients with DCM, surpassing routine and dedicated functional parameters. Thus, CMR strain imaging may contribute to the improvement of risk stratification in DCM.The online version contains supplementary material available at 10.1186/s12968-021-00829-x. As the assessment of myocardial deformation provides incremental prognostic value in heart failure , 2, a beCardiovascular magnetic resonance (CMR) allows for the assessment of cardiac morphology and function with high spatial resolution and an excellent intrinsic blood-to-tissue contrast . It is rPrevious studies showed, that global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS) and LV torsion are altered in various cardiomyopathies , 16. AltTherefore, the aim of this study was to assess GLS, GCS, GRS and LV torsion in a large, multicenter cohort of DCM patients, and to evaluate their prognostic value.Diagnosis of DCM was based on the 1995 World Health Organization/International Society and Federation of Cardiology criteria [A population of 410 patients with non-ischemic DCM from University Hospital Heidelberg and the EuroCMR Registry was screened. In 45 patients the minimum interval of one year for follow-up data was not reached resulting in exclusion. Another 15 subjects were excluded due to insufficient tracking quality. Finally, a study population of 350 DCM patients was retrospectively included in the study. 306 patients derive from University Hospital Heidelberg, the 44 patients of the EuroCMR Registry from four different imaging centers in Switzerland, Belgium and Lithuania.In addition, 70 subjects drawn from a study population of proven healthy subjects were analysed at University Hospital Heidelberg. They all underwent a strict selection process including detailed medical history, physical examination, comprehensive blood tests, 12-lead electrocardiogram (ECG) and stress CMR. An oral glucose tolerance test was performed to exclude impaired glucose tolerance. Subjects with a history, signs or symptoms of a cardiac disease were excluded. Additional exclusion criteria were arterial hypertension, cerebrovascular or other relevant diseases, a regular intake of drugs except for thyroid or contraceptive drugs or vitamins.All participants gave written informed consent and the study was approved by the local ethics committee. A part of the study population was already part of prior CMR trials , 20.®, Philips Healthcare, Best, the Netherlands). Subjects identified from the EuroCMR Registry were examined at various 1.5T and 3T CMR scanners from Philips Healthcare  and Siemens Healthineers . Image acquisition was performed in accordance with the Society for Cardiovascular Magnetic Resonance (SCMR) guidelines to allow for data pooling [CMR examinations at the University Hospital Heidelberg were performed on a 1.5T clinical scanner  and dedicated CMR software  at our imaging center from different examiners with many years of expertise in CMR. All ‘standard’ morphological and functional parameters including late gadolinium enhancement (LGE) were analyzed in accordance with actual recommendations [Analyses of all subjects for ventricular volumes, LVEF and other morphological and functional parameters were derived from short axis and long axis views on commercially available workstations  at the core lab of the University of Heidelberg. LV endocardial and epicardial borders were manually drawn at end-diastole and the tracking of the myocardium over the whole cardiac cycle was automatically conducted. All measurements were repeated three times . If neceApical and basal slices at standardized 25% and 75% levels were selected for the quantification of rotational parameters, as this approach provides best reproducibility . As viewprimary endpoint. The events of the primary endpoint and hospitalization due to heart failure were defined as the secondary endpoint. In case of simultaneous cardiac events per patient, the worst event was selected . There was lack of follow-up data from 45 patients from the EuroCMR Registry.Physicians, blinded to the CMR results, contacted each patient or an immediate family member to obtain follow-up data. Cardiac death, heart transplantation and aborted sudden cardiac death (SCD) by appropriate implanted cardioverter defibrillator (ICD) discharge (including successful antitachycardia pacing = ATP) due to ventricular tachycardia or ventricular fibrillation were defined as the combined Continuous parameters were expressed as mean ± standard deviation for parametric and as median with interquartile range (IQR) for nonparametric variables. Normal distribution was assessed using Shapiro–Wilk test. To compare continuous variables between two groups, Student’s t-test and Mann Whitney U test were used as applicable. Categorical variables were expressed as counts and proportions and were compared using the Chi-square test. The Kaplan–Meier method was used for survival curves, which were compared by log-rank tests. Receiver operating characteristics analysis was used to define optimal cut-off values for the prediction of clinical endpoints. Univariate and multivariate Cox proportional hazards regression analyses were performed to calculate hazard ratios (HR) and 95% confidence intervals (CI). Collinearity was examined using a correlation matrix of correlation coefficients (r) for the observed parameters after the method of Pearson et al. for parametric and Spearman et al. for non-parametric parameters. Intra- and interobserver variabilities for GLS, GCS, GRS and LV torsion were assessed by repeated analysis of 20 randomly selected patients of the control group and 20 DCM patients. The intra- and interobserver variability was described using the intra-class correlation coefficient (ICC with 95% CI) with a two-way random model with absolute agreement. A p-value of < 0.05 was regarded as statistically significant. Dedicated statistical software MedCalc  was used for statistical analysis.The final study population consisted of 350 subjects . There were no significant differences regarding age and gender between the DCM- and the control group , while age  and gender  were similar.without LGE.In the DCM subgroup with LGE (n = 134); GLS , GCS , GRS  as well as the LVEF  but not LV torsion  were significantly reduced compared to DCM patients In contrast to the healthy control group (p < 0.001), a considerable fraction of DCM patients showed a reversed direction of rotation (45.4%), predominantly affecting the LV apex . Instead of a counterclockwise apical rotation, what is regarded to be normal in systole, these patients showed a peak clockwise rotation of the apex resulting in a systolic rotation of apex and base into the same direction. Compared to DCM patients with normally directed rotation, the patients with reversed apical rotation had a significantly lower LVEF . Regarding LV strain and LV rotation, especially LV torsion was impaired . In the group of reversed apical rotation, a larger proportion of patients had a left bundle branch block (LBBB) compared to the group of patients with normally directed rotation . Consequently, QRS duration was significantly prolonged in patients with reversed apical rotation . Thereby, reversed rotation of the LV apex provided high specificity  for the diagnosis of DCM.Some subjects of the control group showed a reversed rotation direction , especially of the LV base. One subject had a reversed apical rotation (1.4%). Clinical, CMR or other LV strain parameters showed no significant differences compared to the subjects with normally directed rotation.Over a median follow-up period of 4.2 (2.0–5.6) years, the primary endpoint was observed in 59 patients (18.7%), the secondary endpoint in 73 patients (20.9%). In total, 84 events occurred: 25 patients experienced a cardiac death, 7 underwent heart transplantation, 28 had an aborted SCD by an appropriate ICD discharge and 24 patients were hospitalized for heart failure.The patients, in whom the primary endpoint occurred, had a significantly impaired LVEF, GLS, GCS, GRS and LV torsion , the primary endpoint was observed in 44 patients (27.5%). In these 44 patients a significantly lower GLS  and GCS  was observed.In contrast, only 15 (7.9%) primary endpoint events were observed in the patient group with an LVEF > 35% (n = 190). GLS , GCS , GRS  and the LV torsion  were lower in these 15 patients—but only as a trend—compared to the other patients with a LVEF > 35%.Several clinical , laboratory (log transformed NT-pro BNP), standard CMR , presence of LGE) and strain parameters  were associated with the primary and the secondary endpoint in univariate analysis , an intermediate risk- 2–5 points) and a high-risk group (6 points). In Kaplan–Meier analysis, each group differed significantly from each other  using FT in CMR featured a good reproducibility in healthy subjects as well as DCM patients  strain and rotational parameters could be assessed reliably using CMR FT with high intra- and interobserver reproducibility. (2) GLS, GCS, GRS as well as LV torsion were significantly impaired in patients with DCM. (3) The analyzed parameters offered a significant prognostic value surpassing standard CMR parameters for risk stratification.The timely diagnosis of DCM and recognition of myocardial dysfunction is important for the initiation of therapy, risk stratification and to reduce mortality . CurrentIn accordance with previous studies on myocardial mechanics in DCM, a reduction of all strain parameters including LV torsion was observed , 26. LV In DCM patients, a more precise prediction of clinical outcome using GLS was reported by several investigators—some of these included patients from our study population , 20, 32.A risk score including six categorical variables of standard CMR and strain parameters allowed for further risk stratification in DCM patients.Remarkably, LGE was an independent predictor of the primary endpoint but not of the secondary endpoint, which additionally includes hospitalization due to heart failure. Of note, GLS was independently associated with both endpoints. Thus, an impaired GLS may represent a better indicator of a worse outcome. Regarding LGE, myocardial fibrosis may not only be a result of an advanced stage of DCM but also increase the risk of adverse events as ventricular arrhythmias.A comprehensive approach assessing both functional parameters including LV strain and tissue composition, as done in this study, may be beneficial in clinical routine.In this respect, we were able to prove the additional prognostic value of LV strain in advanced disease stages even in our subgroup analysis: in patients with a LVEF ≤ 35% (n = 160), GLS and GCS were still significant predictors of the primary endpoint. Since the identification of patients eligible for an ICD remains challenging, especially in non-ischemic cardiomyopathies as shown by the DANISH study, the addition of strain parameters may improve the risk stratification .LV rotation prognostic data are scarce and to our knowledge, we provide the first prognostic data of CMR LV torsion in DCM. The direction of apical rotation may be a hallmark of DCM as many patients showed a reversed apical rotation. The pathogenesis of reversed apical rotation is unclear, though in our study population these patients had significantly more often a LBBB than patients with normal directed rotation. LV rotational mechanics might be influenced by a changed propagation of cardiac excitation: former studies reported of a delayed activation of apical myocardium and an ‘U-shaped’ activation from right to left of at first anterior epicardium followed by septum and then of the lateral wall in patients with LBBB , 35. It In patients with DCM a reversed apical rotation has been reported, however its prognostic potential was previously unknown , 26. In In another study, Rady et al. previously showed an incremental value of LV torsion assessed with speckle-tracking echocardiography compared to right ventricular function and peak VO2 for the prediction of cardiac events in 91 DCM patients and a median follow-up of 272 days .As we were able to prove in this study, LV torsion as a rotational parameter had a significant prognostic value, which, however, is lower than other strain parameters like GLS or GCS. Thereby, GLS and GCS represent the strongest strain parameters with regard to their prognostic value.CMR FT provides quick and reliable global strain and rotational values with good intra- and inter-observer variability , 37, 38.The application of fully automated software approaches for strain analysis could accelerate this development even further .CMR FT strain analysis has been previously validated, but there are no data on the agreement of LV rotational measurements between CMR FT and CMR tagging. There are only feasibility studies using CMR FT to assess LV rotation , 44. In As part of the study population was drawn from the EuroCMR Registry, the quality of clinical and CMR-derived data of these patients were dependent on the respective institution. Due to the lack of follow-up data, 45 patients of EuroCMR Registry had to be excluded resulting in a predominance of a single center.Because NT-pro BNP values were only available in 68.5% of the DCM patients, its prognostic value is possibly underestimated. As we showed a strong correlation between LVEF, GLS and GCS, there is a certain collinearity among the different parameters.A priori power analysis regarding the prognostic value of LV torsion was not possible due to missing prognostic data. As rotational parameters were significant predictors in the univariate but not the multivariate analyses, one could speculate that they might have become statistically significant in a larger study population. However, the clinical relevance of such small effects would be questionable.In patients with DCM, global LV strain parameters showed an additive prognostic value. Especially GLS surpassed standard clinical and CMR-derived parameters in the risk stratification of DCM patients. GLS and GCS add further prognostic information in DCM patients even in subjects with a LVEF ≤ 35%. The DCM risk score as a simple scoring system including standard CMR- and strain parameters allows for an exact risk stratification in DCM patients. With its additional prognostic value, an easy-to-use, fast and reproducible assessment of strain and rotational parameters, CMR FT may aid in risk stratification of DCM patients—and may find its way to routine clinical application. Larger, prospective multi-centre trials, using a comparable global strain approach, are needed to confirm our findings.Additional file 1: Table S1. Correlation matrix for correlation coefficients (r) of common CMR and strain parameters including LV torsion. LVEF: left ventricular ejection fraction; GLS: global longitudinal strain; GCS: global circumferential strain; GRS: global radial strain; LV torsion: left ventricular torsion; LVEDV: left ventricular end-diastolic volume. Table S2. Univariate survival analysis of the secondary endpoint . HR: hazard ratio; CI: confidence interval; LVEF: left ventricular ejection fraction; LVEDV: left ventricular end-diastolic volume; NT-pro BNP: N-terminal pro-hormone brain natriuretic peptide; LGE: late gadolinium enhancement; GLS: global longitudinal strain; GCS: global circumferential strain; GRS: global radial strain. Table S3. Multivariate survival analysis of the secondary endpoint . HR: hazard ratio; CI: confidence interval; LVEF: left ventricular ejection fraction; LVEDV: left ventricular end-diastolic volume; LGE: late gadolinium enhancement; GLS: global longitudinal strain; GCS: global circumferential strain; GRS: global radial strain. Table S4a. Intra- and Interobserver variability of the strain parameters in healthy individuals. ICC: intra-class correlation coefficient; CI: confidence interval; GLS: global longitudinal strain; GCS: global circumferential strain; GRS: global radial strain; LV: left ventricular. Table S4b. Intra- and Interobserver variability of the strain parameters in DCM patients. ICC: intra-class correlation coefficient; CI: confidence interval; GLS: global longitudinal strain; GCS: global circumferential strain; GRS: global radial strain; LV: left ventricular.Additional file 2: Figure S1. Kaplan–Meier analysis of a CMR risk score for the prediction of the secondary endpoint. CMR risk score is based on different CMR  and strain parameters for the prediction of the secondary endpoint in DCM patients. Cut-off values as mentioned in Fig. Figure S2. Kaplan–Meier analysis of a simplified CMR risk score in DCM patients. The simplified CMR risk score is based on LVEF, LGE and GLS as the single strain parameter for the prediction of the primary endpoint (cut-off values as mentioned in Fig.


Mapping of left ventricular (LV) native T1 is a promising non-invasive, non-contrast imaging biomarker. Native myocardial T1 times are prolonged in patients requiring dialysis, but there are concerns that the dialysis process and fluctuating fluid status may confound results in this population. We aimed to assess the changes in cardiac parameters on 3T cardiovascular magnetic resonance (CMR) before and after haemodialysis, with a specific focus on native T1 mapping.This is a single centre, prospective observational study in which maintenance haemodialysis patients underwent CMR before and after dialysis (both scans within 24 h). Weight measurement, bio-impedance body composition monitoring, haemodialysis details and fluid intake were recorded. CMR protocol included cine imaging and mapping native T1 and T2.Twenty-six participants  were included in the analysis. The median net ultrafiltration volume on dialysis was 2.3 L , resulting in a median weight reduction at post-dialysis scan of 1.35 kg , with a median reduction in over-hydration (as measured by bioimpedance) of 0.75 L . Significant reductions were observed in LV end-diastolic volume , LV stroke volume , global T1 , global T2  following dialysis. There was no change in LV mass (p = 0.35), LV ejection fraction (p = 0.13) or global longitudinal strain (p = 0.22). On linear regression there was no association between baseline over-hydration (as defined by bioimpedance) and global native T1 or global T2, nor was there an association between the change in over-hydration and the change in these parameters.Acute changes in cardiac volumes and myocardial native T1 are detectable on 3T CMR following haemodialysis with fluid removal. The reduction in global T1 suggests that the abnormal native T1 observed in patients on haemodialysis is not entirely due to myocardial fibrosis.The online version contains supplementary material available at 10.1186/s12968-021-00822-4. Patients with chronic kidney disease (CKD) are at a greatly increased risk of cardiovascular disease (CVD) . This riCardiovascular magnetic resonance imaging (CMR) is established as the reference method for imaging uraemic cardiomyopathy . PreviouNative T1 mapping is a non-contrast technique that estimates myocardial longitudinal relaxation times (ms) and reflects changes in extra- and intra-cellular compartments. Myocardial T1 is commonly affected by changes in collagen (fibrosis), water (oedema), iron deposition  and lipids (Anderson-Fabry’s disease) . In addiParticipants were aged > 40 years and were established on regular, day-time hospital-based haemodialysis for at least 6 months. Participants were eligible for inclusion if they had a history of recurrent fluid overload  and without heart failure  (> 50%) on their most recent transthoracic echocardiogram). Participants had to be able to comply with study procedures, self-report an ability to lie flat for 1 h and provide informed consent. Exclusion criteria included standard contra-indications to CMR and contraindications to iodine based radiological contrast (to facilitate a sub-study comparing CMR with a novel contrast CT technique) , 27. TheThis single centre observational study consisted of 2 visits Fig. . Visit 1CMR acquisition was performed at the Clinical Research Imaging Facility of the Queen Elizabeth University Hospital in Glasgow using a 3 T CMR scanner  with an 18-channel surface coil placed anteriorly and a 32-channel spine coil placed posteriorly. Following the acquisition of localiser images, balanced steady state free precession sequences were used to acquire LV cine imaging in three long axis planes, followed by a short axis stack from the apex to the atrio-ventricular ring, each with 25 phases. Images were obtained using retrospective electrocardiogram (ECG)-gating at end-expiration. Where participants were unable to breath-hold or had cardiac arrhythmia, compressed sensing  was used to allow real-time acquisition. Typical scan parameters were: field of view (FOV) 340 × 286 mm, slice thickness 7 mm with 3 mm gap in short axis stack, repetition time (TR)—41.4 ms, echo time (TE) 1.51 ms, flip angle 50°, voxel size 1.33 × 1.33 × 7 mm.For native T1 and T2 mapping, basal, mid and apical short axis views were acquired using SiemensMyoMaps sequences. For native T1, non-contrast, motion-corrected, optimized, modified Look-Locker inversion recovery sequences were used with the following typical parameters: FOV 340 × 272 mm, slice thickness 6.0 mm, voxel size: 1.9 × 1.9 × 6.0 mm, TR 272 ms, TE 1.12 ms, flip angle 35 degrees, minimum T1 100 ms, inversion-time increment 80 ms, bandwidth 1085 Hertz/pixel. For T2 mapping, three T2 weighted measurements were acquired followed by an automated exponential fit for each pixel after respiratory motion correction. The imaging used a T2-prepared single shot balanced steady state free precession readout with T2 preparation times (TE) = 0, 25, and 55 ms with a recovery period of 3 heartbeats between measurements. Typical protocol parameters for T2 mapping were: FOV 360 × 270 mm, slice thickness 8 mm, matrix 192 × 108, spatial resolution 1.9 × 2.5 mm, TR 207.39 ms, TE 1.32 ms, flip angle 12 degrees, bandwidth 1184 Hz/pixel.All CMR scans were subject to a clinical report for clinical governance purposes. Research CMR analysis was performed utilizing dedicated CMR software ). Routinely reported CMR measures of LV and right ventricular (RV) function were carried out according to current guidelines . ParametContinuous data with a normal distribution are presented as mean ± standard deviation (SD), and median and interquartile range (IQR) for skewed data, with normality defined according to Shapiro–Wilk test. Pre and post dialysis CMR values were compared using paired t-tests and Wilcoxon singed rank tests accordingly. Linear regression and multiple regression were used to compare change in CMR parameters according to baseline variables. Repeated measures MANCOVA was used to account for covariates in the comparison of myocardial native T1 before and after dialysis. Intra- and interobserver variability was assessed by the intra-class correlation (ICC) coefficient . Statistical analysis was performed, and figures created, using SPSS .A prospective sample size calculation determined that a total of 9 participants would be required to detect a 2.5% difference in native T1 times with 80% power and alpha 0.05 based on previously published data , 21. A tTwenty-eight participants were recruited between 19th October 2018 and 9th March 2020. Recruitment was stopped early (target n = 30) due to the COVID-19 pandemic. Two participants withdrew consent prior to any study procedures leaving 26 for analysis, of whom 16 (61.5%) were male, 22 (84.6%) were white and age 64.7 ± 9.4 years. Median duration of kidney replacement therapy at time of recruitment was 2.0  years. Multi-morbidity was prevalent in the cohort with a mean Charlson Comorbidity index of 6 (mean modified Charlson Comorbidity Index of 3) , 32. TheAll participants had a history of recurrent fluid overload with mean ultrafiltration volume of 2.2 L (± 0.4) from the preceding 3 dialysis sessions prior to recruitment. At visit 1 , 12 participants had demonstrable pitting oedema. 1 participant was unable to undergo bioimpedance monitoring for multifactorial reasons . Of the remaining 25 participants, the median over-hydration was + 0.4 L , with 10 participants measuring as volume deplete pre-dialysis. The median net ultrafiltration volume on dialysis was 2.3 L  at a mean rate of 6 mL/kg/h (± 1.7). Five participants experienced symptomatic intradialytic hypotension requiring adjustment of their dialysis prescription. Between visit 1  and visit 2 , the median estimated fluid intake was 0.9 L . At visit 2 , the median reduction in body weight was 1.4 kg , with a median reduction in over-hydration of 0.8 L . No participants gained weight between visit 1 and visit 2, albeit 2 participants’ weight did not change. According to bioimpedance monitoring, 3 participants increased their over-hydration between visits (range 0.2–0.4 L).Table 2 = 0.247, p = 0.013) but there was no association between the change in blood pool T1 and the change in overhydration. There was also no correlation between the change in in myocardial native T1 time and the change in blood pool T1 , nor the change in haematocrit . On repeated measures MANCOVA, when the change in blood pool T1 and the change in haematocrit were added as covariates to the comparison of myocardial native T1 time, there was no significant interaction between either covariate and the change in myocardial native T1. Both covariates had small, non-significant contributions to the observed effect ; change in haematocrit , resulting in an adjusted p-value of 0.050 for the comparison of myocardial naïve T1 before and after dialysis. Additional determinants of blood T1 are examined in Additional file On linear regression there was no relationship between baseline over-hydration and global native T1, septal T1 or global T2 Fig. . There wThere was no association between the change in global native T1, septal T1 or global T2 and the time from dialysis until repeat CMR . Eighteen participants were on a morning dialysis schedule, whereas 8 were on an afternoon schedule and thus scanned at different times of day. The mean difference in myocardial native T1 pre/post dialysis was 25 ms in the morning group (n = 8) and 20 ms in the afternoon group (n = 18), with no significant difference between the groups (p = 0.80). When the T1MES phantom was scanned on consecutive days the measured T1 was 1216 ± 8 ms and 1215 ± 13 ms, respectively. The same values for T2 were 80.8 ± 0.9 ms and 80.2 ± 1.9 ms. There was no difference in global T1, septal T1 or global T2 in those participants who experienced symptomatic intradialytic hypotension versus those who did not . All but 1 participant were prescribed regular intravenous iron therapy. Excluding the 5 participants who received intravenous iron between visit 1 and visit 2 did not change the results . At lower baseline LVEF, repeat LVEF was more likely to increase, whereas those who had a longer gap between visit 1 CMR and dialysis were more likely to have a reduction in LVEF at visit 2 (Fig. There was no overall change in LVEF following dialysis Table . Six part 2 Fig. .Fig. 5ScThis prospective study identified significant changes in cardiovascular parameters on 3T CMR in response to haemodialysis with fluid removal. Specifically, LV and RV end-diastolic volumes, stroke volumes, and atrial volumes reduced, as did global native T1, septal native T1 and global T2 times but not LV mass. There was no correlation between the change in these parameters and the change in fluid status measured by bodyweight or bioimpedance. The change in myocardial native T1 time was independent of changes in haematocrit and blood pool T1, suggesting that the observed difference is not explainable by reduced intravascular T1 time. Regardless of whether the change in native T1 time is due to fluid removal, or the dialysis process itself, the present results question the validity of native T1 mapping as a surrogate marker for myocardial fibrosis in patients on haemodialysis.Native T1 mapping is an appealing potential biomarker for myocardial fibrosis, with proven superiority over volumes, function and late gadolinium enhancement in patients with non-ischaemic dilated cardiomyopathy , 35, andThe minimal clinically significant change in native T1 time is difficult to define. Previous studies comparing native T1 in patients on dialysis versus controls found a mean difference of 21 ms on 1.5T  and 185 Native T1 predicts outcome in patients with heart failure  and acutGlobal T2 times reduced following dialysis with fluid removal, in keeping with previous studies . The natThere appears to be a complex relationship with regards to parameters of ventricular function and dialysis with fluid removal. A study using intradialytic CMR has previously shown that LVEF drops acutely during dialysis with incomplete recovery evident at 1 h post dialysis . This exThis study addresses important questions in relation to 3T CMR to inform timing of clinical scanning in relation to dialysis and the potential bias of fluid overload in parametric mapping. The cohort is representative of the wider dialysis population with high prevalence of comorbidity and no changes to their prescribed dialysis session. The number of clinically relevant incidental findings that were identified is striking but is in keeping with previous reports . Fluid aAcute changes in cardiac volumes and myocardial composition are detectable on 3T CMR following haemodialysis with fluid removal. Accordingly, the timing of clinical CMR scanning in relation to a patient’s dialysis schedule is crucial, particularly if serial scanning is required. Small, but significant, reductions in global myocardial T1 and T2 relaxation times were observed after dialysis suggesting that the abnormal native T1 signal in patients undergoing haemodialysis is not entirely due to fibrosis. The exact mechanism for the reduction in native T1 is unclear. Despite the lack of association with the change in native T1 and the change in fluid status, alterations in tissue oedema remain the most likely explanation, albeit removal of uraemic factors or the haemodynamic effects of dialysis itself may also contribute. Future studies examining the prognostic capabilities of native T1 in CKD populations are still warranted but will require careful standardisation of imaging schedules and awareness of the potential confounding effect of fluid status and the dialysis process.Additional file 1.Supplementary material: S1. Baseline characteristics of participants. S2. Summary of clinically significant incidental findings. S3. Intra- and inter-observer reproducibility for cardiovascular MRI parameters. S4. Determinants of blood pool native T1. S5. Analyses exploring the potential influence of intravenous iron therapy on native T1.


Restrictive cardiomyopathy (RCM) is a common myocardial disease in cats, characterized by diastolic dysfunction and atrial enlargement without myocardial hypertrophy. Especially, endomyocardial form of RCM, one of the subtypes in RCM, is characterized by endocardial fibrosis, endocardial scar bridging the interventricular septum and left ventricular (LV) free wall, and deformation and distortion of the LV. However, it is unclear how the myocardial dysfunction and the endocardial scar contribute to the pathophysiology of RCM disease progression.A 3 years and 2 months old, intact male, Domestic shorthaired cat was presented for consultation of cardiac murmur. At the first visit (day 0), the notable abnormal finding was echocardiography-derived chordae tendineae-like structure bridging the interventricular septum and the LV free wall, resulting high-speed blood flow in the left ventricle. Electrocardiography, thoracic radiography and noninvasive blood pressure measurements were normal. No left atrial enlargement was observed, and LV inflow velocity showed an abnormal relaxation pattern. Although there was no abnormality in tissue Doppler imaging-derived myocardial velocity, two-dimensional speckle tracking echocardiography (2D-STE) revealed a decrease in the LV longitudinal strain and an increase in endocardial to epicardial ratio of the LV circumferential strain on day 0. On day 468, obvious left atrium enlargement and smoke like echo in the left atrium were observed. The LV inflow velocity was fused, and the tissue Doppler imaging-derived early-diastolic myocardial velocity of the septal mitral annulus decreased. Regarding 2D-STE, LV circumferential strain was further decreased, and right ventricular strain was additionally decreased. Although the general condition was good, we made a clinical diagnosis of endomyocardial RCM based on the above findings. On day 503, the cat showed the radiographic evidence of pulmonary edema and congestive heart failure signs.Cats with abnormal LV structure and associated myocardial dysfunction like this case needs careful observation. Additionally, 2D-STE indices may be useful for early detection of myocardial dysfunction in feline RCM. Restrictive cardiomyopathy (RCM) is a common myocardial disease in cats, characterized by diastolic dysfunction and atrial enlargement without myocardial hypertrophy –4. EspecConventional two-dimensional and Doppler echocardiography are used for the clinical diagnosis of feline RCM , 2, 5. AIn this report, we describe a cat that did not meet the diagnostic criteria of RCM assessed by conventional echocardiography on the first visit, but had myocardial dysfunction assessed by layer-specific 2D-STE, and report the utility of layer-specific 2D-STE for early detection of feline RCM.An intact male, domestic shorthaired cat, aged 3 years and 2 months and weighing 4.8 kg, was brought to Nippon Veterinary and Life Science University for a consultation regarding a cardiac murmur. At the first visit (day 0), the cat had no history of relevant clinical signs. On auscultation, a systolic murmur (Levine II/VI) was detected. Electrocardiography, thoracic radiography, and noninvasive blood pressure measurements (systolic blood pressure 125 mmHg) revealed no abnormalities. Conventional two-dimensional and Doppler examinations were performed using a Vivid E95 echocardiographic system , and analyzed using an offline EchoPAC workstation  –14. The On day 89, a decrease was noted in LV-SL and LV-SC at PM, and the early-diastolic LV-SrC PM was found to be below the 25th percentile of the 15 healthy cats. However, since no significant changes were observed in the general condition and echocardiography, no treatment was started.On day 468, although there were no clinical signs, substantial left atrial (LA) enlargement based on LA to aortic root diameter ratio and smoke-like echo in the LA were observed. The end-diastolic LV internal dimension had increased. We also noticed an increase in heart rate 238 bpm). Although the high-speed blood flow in the left ventricle had increased to 4.3 m/s, fused E and A 0.65 m/s), and diastolic dysfunction based on early-diastolic myocardial velocity of the septal mitral annulus (E’) were observed. Regarding 2D-STE, LV-SC and LV-SrC AP were severely decreased, and the epicardial LV-SC PM, systolic LV-SrC PM, and whole and epicardial RV-SL were additionally below the 25th percentile of the 15 healthy cats . On day 523, the general condition of the cat was good.We reported the early detection of myocardial dysfunction by 2D-STE which conventional echocardiography could not detect on day 0. In present, clinical diagnosis of RCM is performed according to the echocardiographic evidence of atrial enlargement and diastolic dysfunction, using LA to aortic root diameter ratio, trans-mitral flow pattern, and TDI. However, trans-mitral flow is often fused due to tachycardia, and angle dependency and loading condition would affect the TDI-derived assessment of the myocardial function. Therefore, conventional echocardiography, including TDI, may be insufficient for the clinical diagnosis of RCM.In this case, we assessed myocardial function using 2D-STE, a newly developed echocardiographic tool to evaluate intrinsic myocardial function. Layer-specific myocardial assessment has been demonstrated to be useful for the early detection of myocardial dysfunction in cats with asymptomatic hypertrophic cardiomyopathy, before the occurrence of LV hypertrophy . At day Layer-specific 2D-STE revealed that endocardial LV-SC PM, and endo/epi in the LV-SC PM and AP were decreased at day 0, which has been reported previously in cats with endomyocardial form of RCM . It has Although LV-SC MV was not impaired, LV-SC PM and AP were below the normal range from day 0. The abnormal LV structure and associated abnormally high-speed blood flow in the middle of the left ventricle due to the abnormal chorda tendineae-like structure may have contributed to further apical myocardial damage through increase in wall stress and myocardial ischemia due to afterload. Therefore, in cats with an abnormal chorda tendinea-like structure in addition to myocardial dysfunction like this case, RCM might progress rapidly and result in congestive heart failure.There were several limitations in this case. First, there is no histopathological findings to make a definitive diagnosis and assess myocardial histopathological alterations. Second, although no medication was given on day 0, the some medications, such as β-blockers and pimobendan, might affect the echocardiographic variables including 2D-STE indices.In conclusion, abnormal LV structure and associated myocardial dysfunction may contribute to the pathogenesis of RCM, disease progression, and heart failure. Cats with these findings, even without LA enlargement, may require careful follow-up. Further research including pathological examination is desired by accumulating the number of cases in the future.