Infective endocarditis (IE) is a disease of the endocardium, which leads to the appearance of vegetation on the valves, cardiac structures, or, potentially, vascular endothelium of the heart. The risk of IE can be increased more than 140 times by congenital heart disease , particularly if cyanotic. An increase in mortality may result from IE in patients with a complex cardiac pathology or patients with an implanted prosthetic material, most frequently conduits in a pulmonary position. Cardiac implantable electronic devices (CIED) infective endocarditis is a life-threatening complication representing 10% of all cases of endocarditis. Common signs of presentation are often fever and chills; redness and swelling at the pocket of the pacemaker, including the erosion and exteriorization of the device; and life-threatening sepsis. The use of intracardiac echocardiography for the diagnosis of IE is an innovative method. This may be needed, especially in older children undergoing complex cardiac surgery, when transthoracic echocardiography (TTE) and transesophageal echocardiography (TOE) failed to provide a reliable diagnosis. The 2018 European Heart Rhythm Association (EHRA) experts’ consensus statement on transvenous lead extraction recommends complete device removal and antimicrobial therapy for any device-related infection, including CIED-IE. The most detected microorganism was Staphylococcus Aureus. In addition, cardiac surgery and interventional cardiology associated with the placement of prostheses or conduits may increase the risk of IE up to 1.6% for Melody valve implantation. Our manuscript presents a comprehensive review of infective endocarditis associated with cardiac devices and prostheses in the pediatric population, including recent advances in diagnosis and management. Infective endocarditis (IE) is a disease of the endocardium, which leads to the appearance of vegetation on the valves, cardiac structures, or, potentially, vascular endothelium of the heart. This disease is estimated to affect 0.43–0.69 cases per 100,000 children . A pre-eAround 90% of children with CHD are expected to survive to adulthood. For some conditions, reintervention may be necessary after initial treatment. There may be a need for prosthetic materials, valve-related interventions, or intracardiac devices under these conditions, contributing to the high risk of IE in this group of patients. IE accounts for approximately 4% of all admissions in a tertiary care facility, and its associated mortality is about 7% ,9. An inIn infective endocarditis, the diagnosis is based on the modified Duke criteria, the current gold standard for diagnosing infective endocarditis, which can be followed in Only specific paraclinical investigations are considered in the major criteria—repeated positive blood cultures for specific germs; echocardiographic images indicating vegetation, an abscess, a perforation, aneurysms, pseudoaneurysms, fistulas, or prosthesis dehiscence; or more recent investigations showing abnormal activity at the implant site of a valve prosthesis, which is detectable by F-FDG PET/CT.There are minor criteria as well, including predisposing factors, fever, and vascular manifestations . Due to children’s relatively minor circulating blood volume, the blood samples should be smaller. Infants and younger children should be limited to 1–3 mL, and older children should be limited to 5–7 mL. Bacteremia is usually constant in IE, so there is no need to expect pyrexia. Isolated growth in a single sample should be cautiously considered because of the high possibility of contamination [The cornerstone for microbiological diagnosis is positive blood cultures identifying the pathogen and the sensitivity to antimicrobial therapy. In order to determine the pathogen responsible for IE, it is imperative that blood samples are collected for microbiological examination as soon as possible from all patients suspected of having IE, especially if a patient is experiencing a fever of unexplained origin, a new heart murmur, a post-implantation device, a post-procedure valvuloplasty, or a previous history of endocarditis. The process involves taking three blood cultures through separate venous punctures on the first day of fever. If there is no rise after two days of incubation, 2–3 more blood samples should be taken . These cmination . It is imination . Staphylmination , while imination . Streptomination ,20,21.Even with advances in microbiological diagnostic techniques, such as polymerase chain reaction and serology, and the sensitivity of the modified Duke classification, approximately 12% of IE cannot be labeled as “definite” .Abiotrophias, Brucellas, Bartonellas, Legionellas, and Mycoplasmas or when intracellular microorganisms such as Coxiella burnetii are the cause. Several types of bacteria require specific culture media and conditions, such as buffered charcoal yeast extract (BCYE) agar for Legionella spp. and L-cysteine-enriched medium for Abiotrophia spp. If fastidious microorganisms or unusual pathogens are suspected, the microbiology laboratory should be strengthened so that more prolonged incubation and more specific tests can be used. Additionally, up to six weeks of incubation may be necessary for slow-growing bacteria in some cases [S. aureus and coagulase-negative staphylococci are more common [Approximately 2.5%–31% of blood cultures remain sterile, especially when antibiotic therapy is pre-administered, in the presence of slow-growing bacteria, including anaerobes, the HACEK group, me cases . Howevere common ,24,25.Usually, transthoracic echocardiography (TTE) can provide sufficient information to recognize the changes and for follow-up. The limitations of TTE can arrive in complex congenital heart disease, especially in patients after cardiac surgery. Moreover, shunts and conduits are challenging to distinguish from other prominent cardiac structures and surgical remnants. This is because it is challenging to distinguish vegetation from such structures. It is estimated that false-negative results can reach 70% for TTE after cardiac surgery with complex CHD . ChildreChildren with congenital heart disease can benefit from transesophageal echocardiography, especially those who have already undergone surgery or intend to undergo surgery for IE in the near future. It is usually necessary to monitor intraoperative cardiac surgery using transesophageal echocardiography. Despite its advantages, transthoracic echocardiography has decreased diagnostic performance in children with structurally normal hearts and negative microbiological tests when the probability of IE is low. A TEE should be conducted in patients with clinical suspicion of IE and a non-diagnostic or negative TTE, a prosthetic valve, or an intracardiac device. It is necessary to repeat this procedure in 5–7 days if there is a high clinical suspicion and a negative initial TEE examination .Therefore, a few specific points need to be considered prior to a transesophageal ultrasound in children. Sedation or general anesthesia may be necessary, and a probe appropriate to the child’s weight should be used . When veIntracardiac echocardiography is a particularly valuable tool in the diagnosis of IE. As previously mentioned, conventional transthoracic and transesophageal echocardiography may have poor diagnostic performance in children with cardiac devices or previous corrective surgery. Intracardiac echocardiography, a very flexible technique, can overcome these limitations ,31,32.18F-FDG. Patients with suspected IE and diagnostic difficulties may benefit the most from these new imaging techniques, which can also be used to monitor response to therapy .Recent years have witnessed an increase in the use of advanced cardiovascular imaging modalities such as magnetic resonance imaging, computed tomography, and single photon emission CT (SPECT)/CT and positron emission computer tomography (PET-CT) with the administration of 111In-oxine or 99mTc-hexamethyl propylene amine oxime) that accumulate in a time-dependent fashion in late images versus earlier images [18F-FDG, which is actively incorporated in vivo by the activated leucocytes, monocyte macrophages, and CD4+ T-lymphocytes accumulating at the sites of infection. The main added value of these new imaging techniques is reducing the rate of misdiagnosing IE in patients labeled as possible IE by the Duke criteria and for detecting embolic and metastatic infectious events [SPECT/CT imaging relies on the use of autologous radiolabeled leucocytes  implantation are widening in adults and the pediatric population. Pacing for congenital heart block is now more common, as indications now include less severe criteria for pacing, such as a mean heart rate of <50, prolongation of QTc, broad QRS escape rhythm, complex ventricular arrhythmias detected on resting ECG or Holter monitoring, syncope, and symptoms during effort. The currently estimated number of active devices has reached 4.5 million, with over 1 million new implants yearly . In the CIED infective endocarditis is a life-threatening complication representing 10% of all cases of endocarditis . Infecti18F-FDG) PET/CT has found its way to improve the diagnostic accuracy of the modified Duke criteria in patients with suspected infective endocarditis with prosthetic valves or cardiac devices [The diagnosis of CIED-IE is complex and requires additional time; one cohort study reported 48 days . The 202 devices . Reports devices , while o devices . Larger The 2018 EHRA expert consensus statement on transvenous lead extractions and the 2020 EHRA international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections recommend complete device removal and antimicrobial therapy for any device-related infection, including CIED-IE ,49. The The most common indication for lead extraction is device-related infection. In one study describing the transvenous removal of 135 leads, 77.8% of extracted leads were for pocket infection, followed by 9.8% for infective endocarditis . TransveCases of IE after cardiac surgery or interventional procedures in children are sporadic. It was observed that IE incidence has increased with the implantation of pacemakers, replacement of intracardiac prosthetic valves, and improved endovascular treatment of patients with IE associated with CHD in recent years . In addiIE in children is rarely studied, and very few data are available from Level III hospitals, including cardiac surgery centers. Based on these data, many IE cases are related to surgery. In a study conducted in Turkey on 45 pediatric patients with IE, 30 had a history of congenital heart disease. At the time of IE, 19 patients had foreign material inside their hearts . After the prosthetic valve was replaced, three months, two years, and eight years passed before the diagnosis of IE was made. As a result of reviewing the whole group of patients following cardiac surgery, it was found that 10% developed IE within six months ,54.In developed countries, IE related to right heart pathology has decreased due to the provision of appropriate cardiac care and cardiac surgery. In contrast, IE related to prosthetic valves affecting the left heart has increased ,57,58,59IE on the non-congenital affected pulmonary valve is rare compared to congenital pulmonary pathologies. Replacing the affected valve or conduit with a bioprosthesis or an allograft/xenograft worked well .Aortic valve repair in children is desirable but only sometimes feasible. An aortic valve replacement in children may involve the use of a mechanical prosthesis or the Ross procedure . In adults, replacement, either surgical or interventional, is associated with several risk factors for IE. These include a younger age, the male gender, a higher body mass index, and an elevated post-deployment gradient .A mitral valve repair may not always be possible, especially in children. It may be necessary for a mitral valve replacement to be performed in children with congenital mitral stenosis, mitral insufficiency, or a repaired atrioventricular septal defect and patients infected with mitral valve endocarditis. Replacement of the mitral valve with a mechanical prosthesis may increase the risk for IE. A 5-year survival rate of 96% and a 10-year survival rate of 80% were expected for patients who avoided postoperative endocarditis .p-valve, and others), and new results are expected. Studies also indicated that the risk of IE is more directly related to the valve tissue  than the valve implantation method. Contegra conduits and Melody valves derived from the same biological substrate demonstrate a significantly higher risk of IE than other biological pulmonary valve substrates  [Reconstruction of the right ventricle ejection tract is a standard procedure, especially in adult congenital heart disease, but it is also becoming more common in children . Dependi valves) ,68. UsuaWhen comparing surgical and transcatheter replacements of the aortic valve over 10 years in England in adults, the surgical cohort had a higher IE incidence rate of 4.8%, compared to 3.6% in the transcatheter cohort using the Edwards Sapien valve . Figure Few reported cases of IE on defect closure devices involve atrial or ventricular septal defects. In the pediatric population, some patients have occurrences at long intervals after the defect has been closed, such as after seven months, two years, or six years. However, IE was also observed after two months of ventricular septal defect interventional closure. The prosthesis’ lack of endothelization causes these complications. The Septal Occluder and Figulla Flex II ASD Occlutech prostheses were used. The device was removed, the defect was surgically repaired, and no other complications occurred. In addition, patients received prolonged antibiotic treatment  69,70,7,72,73.Antimicrobial therapy is required to manage IE, focusing on antibiotics for a prolonged period. The choice of antibiotic and the duration of the administration is based on the causative pathogen, potential antibiotic resistance, and type of infected material, whether native tissue, prosthetic valve, or cardiac device . The antS. aureus remains the dominant causative pathogen in children and adults [Streptococcus viridans is the most common cause [The pathogens involved range depending on the underlying conditions. In addition, there have been several changes in the epidemiology of IE in recent decades. Worldwide, d adults . Infectid adults . Particud adults ,31. Neveon cause ,19,32. Won cause ,76.Evidence for antibiotic prophylaxis to prevent IE is based on observational data suggesting that invasive dental procedures or oral procedures may increase the risk of IE in patients at high risk of IE. Antibiotic prophylaxis may decrease this risk. However, the benefit of antibiotic prevention has yet to be definitively established, even in extensive clinical studies ,77,78.By 2021, the AHA published a statement reviewing the impact of the 2007 guidelines on the incidence and outcomes of IE due to viridans group streptococci, with additional recommendations on the use of antibiotic prophylaxis . The 201The frequency of IE limits the benefits of antibiotic prophylaxis without an identifiable prior procedure, the low rate of IE following invasive dental procedures without precaution, and the failure potential of prevention. Thus, it was estimated that even if antibiotic prevention is fully adequate, less than 10% of all endocarditis cases could be prevented by using antibiotic therapy before procedures . In addiThe antibiotic therapy depends on the type of microorganism, the susceptibility of the antibiogram, and the risk factors of the patient, including underlying cardiac disease. Regarding the duration of antibiotic treatment, it should generally be extended in patients with prosthetic valves or corrective surgery with the implantation of prosthetic materials ,17. IntrOutpatient treatment could be considered in children without complications or high-risk factors; in children with negative control blood cultures, who remain afebrile; and in children whose therapeutic adherence, parental cooperation, and close supervision by parents and a home nurse can be guaranteed ,82,83.Empiric antibiotic therapy should be started as soon as possible in critically ill patients without an available antibiogram or in cases with negative blood cultures.When starting treatment for a patient with prosthetic valve endocarditis, it is necessary to identify the causative microorganism, select the appropriate antibiotic, assess the possible complications of endocarditis, and evaluate the need for surgery when antibiotic treatment fails if the infection causes a valve abscess.Empiric antibiotic treatment should be started after obtaining three blood cultures. This treatment should aim to cover Gram-positive and Gram-negative bacteria. This empirical treatment should include vancomycin, gentamicin, and carbapenem or anti-pseudomonal cefepime. When the causative microorganism is identified, treatment should be tailored to cover this causative agent. The American Heart Association recommends at least six weeks of antibiotic treatment ,79.Through this overview, we highlight the importance of prevention in patients at high risk of infective endocarditis, which can often be life-threatening, and the need to develop comprehensive guidelines for these patients. The modern management of IE and CIED-IE prostheses, conduits, or defect closure devices requires a proper and collaborative integration of diagnostic tools and therapeutic strategies. Multimodal imaging is a crucial part of diagnosis, where different techniques provide additional and unique information. Clinicians and imaging specialists should be aware of the strengths and limitations of each approach to appropriately interact with other specialists and, therefore, optimize patient management and improve outcomes.


The ischemic group also experienced more cardiac-related-rehospitalizations . In a multivariable Cox regression model, dyslipidemia, reduced left ventricular ejection fraction, ST-elevation at the hospitalization, and the LGE transmural pattern were the independent predictors of cardiac-related rehospitalizations. Conclusions: In a contemporary cohort of MINOCA patients who underwent CMR, ischemic and non-ischemic patterns had distinct features and outcomes. Among the MINOCA patients, CMR can identify patients at higher risk who require more aggressive therapeutic approached and strict follow-up.Background: To analyze the characteristics and prognosis of a contemporary cohort of patients with myocardial infarction with non-obstructed coronaries (MINOCA) were referred for cardiac magnetic resonance (CMR) imaging, focusing on late gadolinium enhancement (LGE) patterns. Methods: We retrospectively examined and prospectively followed up with 135 patients  undergoing CMR imaging due to a MINOCA diagnosis from 2014 to 2016. We grouped and analyzed the sample according to ischemic  and non-ischemic LGE patterns. The primary outcome was cardiac-related death; the secondary outcome was a composite of cardiac-related rehospitalizations, the new occurrence of acute myocardial infarction (AMI), heart failure (HF), or arrhythmias. Results: CMR exams were performed after a median of 28 days from the acute event. One-third of the ischemic MINOCA were first managed as myocarditis, while CMR helped to adopt a different therapy regimen in 22% of patients (30/135). After a median follow-up of 2.3 years, more cardiac-related deaths occurred in the ischemic than non-ischemic group (2 vs. 1,  Myocardial infarction with non-obstructive coronary arteries (MINOCA) is conventionally represented by an acute myocardial infarction (AMI) with no angiographic obstructive coronary artery disease: stenosis ≥ 50% diameter in a major coronary epicardial vessel .MINOCA is found in about 5–6% of all patients with acute coronary syndromes referred for coronary angiography, ,2 with aThe recently released 4th Universal Definition of Myocardial Infarction stated that the diagnosis of MINOCA requires an underlying ischemic mechanism . In thisOn the other hand, very few studies excluded specific non-ischemic diseases as myocarditis, cardiomyopathies, and Takotsubo syndrome (TTS) ,11. The We reviewed 250 medical records of patients admitted to our department due to a MINOCA diagnosis from 2014 to 2016 that underwent a CMR exam; then, we enrolled patients according to our inclusion/exclusion criteria.N = 20) and patients with a previous history of myocardial infarction (N = 45) or cardiomyopathies (N = 15). We also excluded participants that ended in a final CMR diagnosis of cardiomyopathy (N = 35): dilated (n = 10), hypertrophic (n = 20), amyloidosis (n = 5). As our analysis was specifically focused on LGE patterns, we excluded all patients with a CMR-confirmed TTS diagnosis at the time of enrollment.Inclusion criteria were acute chest pain at the hospital admission, with new or presumed new significant ST-T changes or new left bundle branch block (LBBB), cardiac troponin rise-and-fall >99th percentile of the upper reference level on serial assessments, and non-obstructive coronary arteries lesions in the angiogram. We excluded all the patients with coronary lesions ≥ 50%  constituted the final sample that was followed-up for a median of 2.3 years through outpatient visits in our outpatient department. The data were collected utilizing the available digitally stored medical records; additional phone calls were made for completeness. The primary outcome was cardiac-related-death, and the secondary outcome was a composite of cardiac-related rehospitalizations and the new occurrence of AMI, heart failure (HF), or arrhythmias.In acquiescence with the Declaration of Helsinki, all enrolled patients gave written informed consent at the time of their evaluation, stating that data and images may be subsequently used for research purposes. Given the retrospective nature of the study, no ethical committee approval was required.The angiographic procedures were done from a radial or femoral arterial access, depending on the age of the patients and vascular access availability. All patients received 5000 IU of unfractionated heparin and 200 μg of nitrates before the insertion of the guidewire to control the vasomotor tone. Basal angiographies were obtained in different angiographic views to better visualize and characterize the coronary anatomy.−1 of body weight. Images were acquired 2–3 min after contrast injection (early gadolinium), whereas LGE images were acquired 10–15 min after contrast injection using a standard inversion recovery segmented gradient echo sequence.All the CMR imaging were performed utilizing a 1.5-Tesla  applying a comprehensive protocol including cine, T2-weighted , and early and late gadolinium enhancement (LGE) sequences. An intravenous gadolinium–chelate contrast agent (gadobutrol) was administered at a dose of 0.1 mmol/kgFor our purposes, we grouped and analyzed the samples according to ischemic  and non-ischemic LGE patterns . The iscRegarding the ischemic pattern, a transmural pattern was defined as an area of enhancement involving more than the 70% of the left ventricular wall; conversely, the focal one was defined as a non-transmural, segmental, and restricted area of LGE involving <30% of the left ventricular wall . MyocardMyocarditis was diagnosed based on fulfilling two of the three Lake Louise Criteria: T2-STIR sequences detecting myocardial edema; early gadolinium sequences detecting hyperemia; or epicardial, intramyocardial , or patchy LGE . The earTTS was diagnosed based on the T2-STIR images detecting myocardial edema and regional wall motion in the mid-cavity or apical distribution with no myocardial LGE, all in accordance with the modified Mayo Clinic criteria ,18.Categorical values are expressed as an absolute number and percentage, while continuous variables as the mean and standard deviation (±SD) or median and interquartile intervals , as appropriate.t-test or non-parametric test, while categorical variables were compared by the χ2 test or Fisher’s exact test when appropriate. The variables that were not normally distributed were compared by the Kruskal–Wallis test. The normal distribution was assessed utilizing the Kolmogorov–Smirnov test.The comparisons between normally distributed, continuous variables across the LGE group patterns, non-ischemic and ischemic , were made utilizing the Student’s p-value less than 0.05 at the univariable analysis entered the multivariable model. The latter were age, sex, the presence of comorbidities, laboratory tests at admission, and the different types of CMR patterns discovered at the CMR exams.Cumulative event-free survival rates over time were obtained using the Kaplan–Meier method. The log-rank test was used to compare the event-free survival curves. Univariable and multivariable associations of risk covariates with mortality were assessed using Cox proportional hazard regression analyses. Only variables with a p-values less than 0.05 were considered statistically significant.All statistical analyses were performed with Stata v14.1 . A CMR exam was performed after a median of 28 days from the acute event. General characteristics, comorbidities and cardiovascular risk factors, laboratory test results, and therapy are presented in n = 43 subepicardial, n = 21 intramyocardial, and n = 16 patchy. One-third of the ischemic MINOCA group were initially managed as myocarditis, while CMR helped to adopt a different regimen of therapy in 22% (30/135) of them, introducing the antiplatelet therapy and statins after CMR.In our cohort of patients, 59% of MINOCA patients had non-ischemic LGE patterns at the CMR exam: Ischemic patients were more often female, older, and with a higher prevalence of hypertension, diabetes mellitus, and dyslipidemia than non-ischemic patients. MINOCA patients showing a transmural LGE pattern at the CMR exam had higher incidences of hypertension and diabetes mellitus, had a history of atrial fibrillation, and presented at admission with ST-elevation .p = 0.36), but it was not statistically significant. The latter were classified as myocardial infarction in one case, for the ischemic group, and two as sudden cardiac death. The ischemic group experienced more rehospitalizations , HF , and AMI recurrences ; meanwhile, the non-ischemic group experienced more arrhythmias . The latter were the new onset of non-sustained ventricular tachycardia (n = 28), ventricular ectopic beats (n = 11), supraventricular/atrial tachycardia (n = 4), heart block of varying degrees (n = 3), and atrial fibrillation (n = 2).After a median follow-up of 2.3 years, more cardiac-related deaths occurred in ischemic than non-ischemic patients , especially in the transmural pattern. On the contrary, the focal and the non-ischemic ones had a better prognosis (log-rank tests: p = 0.002) (The ischemic group presented the worst prognosis (log-rank test: = 0.002) .p < 0.001], ST-elevation at hospitalization , reduced left ventricular ejection fraction , and the LGE transmural pattern  were the independent predictors of the secondary outcome ,  outcome .In our study, we found that MINOCA patients presenting an ischemic CMR pattern were more often female, with more comorbidities and risk factors, including hypertension, diabetes mellitus, and dyslipidemia. One-third of the ischemic MINOCA patients were initially managed as myocarditis, while CMR helped to adopt a different regimen of therapy. More cardiac-related deaths occurred in the ischemic than non-ischemic group, and the ischemic group experienced more rehospitalizations, HF, and AMI recurrences, while the non-ischemic group had more arrhythmias. Accordingly, dyslipidemia, reduced left ventricular ejection fraction (<50%), ST-elevation at hospitalization, and the LGE transmural pattern were found to be independent predictors of rehospitalizations, HF, and AMI recurrences.p < 0.001) [These findings support the concepts that MINOCA patients presenting an ischemic LGE pattern at the CMR evaluation have different characteristics and outcomes than non-ischemic ones.  In parti< 0.001) . The hig< 0.001) ,21.To the best of our knowledge, this is the first study focused on the prognostic role of LGE patterns in a population of patients presenting with MINOCA. Moreover, it adds to previous literature that discriminates between MINOCA from an ischemic mechanism of myocardial injury and from a non-ischemic one (mimicking MINOCA). This is of particular interest considering the different therapy regimens that should be adopted in these cases and the uncertainties regarding the optimal medical therapy in MINOCA, particularly the ischemic ones ,23.It has been largely demonstrated the role of CMR in establishing a diagnosis or sorting out a previous misdiagnosis of myocardial infarction, as well as its utility in the context of the “working diagnosis” of MINOCA ,19. DastThe prognosis of patients presenting with MINOCA depends strongly on the underlying cause and the use of its corresponding therapy ,24. In tIn conclusion, as already stated in the American Heart Association (AHA) and the European Society of Cardiology guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation, MINOCA should be considered a working diagnosis, and the etiology pursued, excluding Takotsubo and myocarditis ,25. In tThe single center design of this study is the principal limitation of the present investigation. Secondly, we adjusted for potential confounders in our analysis, but we cannot exclude residual confounding.We only considered patients which underwent CMR, whereas it is possible that the inclusion of patients with suspected MINOCA who did not receive CMR could have biased our results; however, the purpose of the study was to analyze the CMR features of patients with the initial working diagnosis of MINOCA, and in our center the vast majority of these patients underwent CMR, although this may not be the routine approach in other hospitals. Moreover, coronary angiographies were not conducted utilizing the new intravascular diagnostic techniques, such as OCT or IVUS.Finally, in treating ischemic MINOCA, it still largely debated whether ACE-Is or betablockers, in addition to antiplatelets agents or alone, can modify the patients’ prognosis; ,23 unforIn a contemporary cohort of MINOCA patients who underwent CMR, ischemic and non-ischemic patterns had distinct features and outcomes. CMR imaging can modify the therapy regimen and stratify the prognosis of ischemic patients hospitalized with a MINOCA diagnosis.


Although reference ranges of T1 and T2 mapping are well established for cardiovascular magnetic resonance (CMR) at 1.5T, data for 3T are still lacking. The objective of this study is to establish reference ranges of myocardial T1 and T2 based on a large multicenter cohort of healthy Chinese adults at 3T CMR.A total of 1015 healthy Chinese adults  from 11 medical centers who underwent CMR using 3T Siemens scanners were prospectively enrolled. T1 mapping was performed with a motion-corrected modified Look–Locker inversion recovery sequence using a 5(3)3 scheme. T2 mapping images were acquired using T2-prepared fast low-angle shot sequence. T1 and T2 relaxation times were quantified for each slice and each myocardial segment. The T1 mapping and extracellular volume standardization (T1MES) phantom was used for quality assurance at each center prior to subject scanning.The phantom analysis showed strong consistency of spin echo, T1 mapping, and T2 mapping among centers. In the entire cohort, global T1 and T2 reference values were 1193 ± 34 ms and 36 ± 2.5 ms. Global T1 and T2 values were higher in females than in males . There were statistical differences in global T2 across age groups (p < 0.001), but not in global T1. Linear regression showed no correlation between age and global T1 or T2 values. In males, positive correlation was found between heart rate and global T1 .Using phantom-validated imaging sequences, we provide reference ranges for myocardial T1 and T2 values on 3T scanners in healthy Chinese adults, which can be applied across participating sites.Trial registration URL: http://www.chictr.org.cn/index.aspx. Unique identifier: ChiCTR1900025518. Registration name: 3T magnetic resonance myocardial quantitative imaging standardization and reference value study: a multi-center clinical study.The online version contains supplementary material available at 10.1186/s12968-023-00974-5. Cardiovascular magnetic resonance (CMR) mapping techniques allow non-invasive assessment of myocardial tissue characteristics and are increasingly routinely used in clinical studies. T1 and T2 mapping allows pixel-wise measurement of T1 and T2 relaxation times of left ventricular (LV) myocardium, as well as T1-derived extracellular volume (ECV) fraction, which can provide additional diagnostic and prognostic information , as wellAlthough both 1.5T and 3T scanners are widely used for cardiac imaging, reference ranges of T1 and T2 relaxation time values at 3T field strength have not been harmonized due to significant technical heterogeneity –11 and dhttp://www.chictr.org.cn/index.aspx. Unique identifier: ChiCTR1900025518). From Sep 2019 to May 2022, a total of 1015 healthy Chinese adults without any known cardiovascular diseases (or other conditions affecting the cardiovascular system) and MRI contraindications were prospectively recruited. General clinical data were collected, including age, sex, height, weight, blood pressure, exercise intensity, personal and family history. Exclusion criteria were as follows: clinically confirmed hypertension; clinically confirmed diabetes; clinically diagnosed familial hyperlipidemia; myocarditis history; definite coronary artery disease; combined with structural heart disease, such as valvular disease , congenital heart disease; previous cardiac surgery; professional athletes or other long-term endurance sports, amateur marathon enthusiasts; clinically confirmed hyperthyroidism or hypothyroidism; combined with malignant tumors; combined with autoimmune diseases; severe lung disease; blood system diseases (including anemia); complicated with severe liver and kidney dysfunction; combined neurological and muscular diseases; drug abuse or addiction; recent (within 3 months) or long-term (more than 6 months) use of cardiovascular drugs; claustrophobia; no informed consent was obtained. Comprehensive physical examination and electrocardiogram were performed on the day of CMR scan.As part of a prospective clinical registry study, participants were recruited from 11 medical centers in China  covering T1 and T2 ranges in the blood and myocardium before and after gadolinium-based contrast agents. Scanning was strictly performed based on the user manual (10.6084/m9.figshare.c.3610175_D1.v1). The temperature of the scanner room was 22 ± 2 ℃. The “Reference” T1 and T2 values  were first acquired using basic single-slice sequences with TR = 10 ms inversion recovery spin echo  for measurement of T1, and single-slice TR = 7000 ms spin echo (SE) (25 TEs from 10 to 250 ms) for measurement of T2. The fitting of T1 relaxation time was performed using Grid Search-RD-NLS-PR algorithm [CMR was performed using 3T scanners  equipped with a 32-channel phased-array body coil. For quality assurance of cardiac parametric mapping at each individual site, the T1 Mapping and Extracellular volume Standardization (T1MES) phantom scans were performed at each center prior to subject scanning. The T1MES phantom contained 9 vials  was used for automatic localization of the long-axis planes and short-axis planes in all the scans to minimize the discrepancy between sites and technicians. T1 mapping was performed with a motion-corrected MOLLI sequence with a 5(3)3 scheme. T1 mapping slices were acquired at three long-axis planes  and three short-axis planes . The typical parameters were as follows: Trufi pulse sequence; linear k-space ordering; TR/ TE = 300 ms/1.15 ms; FA = 35°; TI = 100 ms; TI increment = 80 ms; FOV = 280 × 360; matrix = 256 × 160; and slice thickness = 8 mm. T2 mapping images were acquired using T2-prepared FLASH sequence in the same planes as T1 mapping. The typical parameters were as follows: centric k-space ordering; TR/TE = 315 ms/1.5 ms; FA = 12°; FOV = 280 × 360; matrix = 256 × 160; slice thickness = 8 mm; and T2 preparation pulses with 0-, 30-, and 55-ms echo times.All images were analyzed in the core laboratory with dedicated postprocessing software . Image analysis was performed by two investigators . T1 and T2 values were measured for each of the 9 vials in identically sized ROIs that occupied the central 50% area of each gel, away from edge-ringing artifacts. T1 and T2 mapping of subjects were analyzed according to the SCMR post-processing guideline . When meTo test the intra-observer and inter-observer variability in T1 and T2 assessment, 50 subjects were randomly selected. Inter-observer variability was analyzed on the same image set by two independent investigators. Intra-observer variability was analyzed on the same image set by one investigator one month later.Statistical analysis was performed using SPSS  and R . Continuous variables were tested for normality using the Kolmogorov–Smirnov test. The reference ranges were defined as ± 2 standard deviation (SD) from the mean. Kendall’s W was performed to verify the consistency of SE, T1 mapping, and T2 mapping among centers. The coefficient of variation (CoV) was defined as the ratio of the SD to the mean. Accuracy was measured in each vial as average of absolute difference between T1 (T2) measurements obtained from SE and each sequence. Precision was measured in each vial as the average of the SD of T1 (T2) measurements obtained with each sequence. T1 and T2 values were compared among age groups  and between sexes. Independent-samples t-tests were used to compare mean values between sexes. One-way analysis of variance or Kruskal–Wallis test were used to compare mean values among three age groups. Linear regression was used for analyses of the relationships between global T1, T2 and age. Intra-observer and inter-observer variability were measured by the CoV, intraclass correlation coefficient (ICC), and Bland–Altman analysis. A two-tailed p value of < 0.05 was considered statistically significant. All the subjects were also stratified by sex and age decades, shown in Additional file The mean rT1, rT2, T1 and T2 values for each vial are shown in Fig. A total of 1015 subjects  were included, the demographic characteristics of study subjects are shown in Table A total of 681 4.2%) myocardial segments for T1 mapping and 912 (5.6%) myocardial segments for T2 mapping were excluded. The reference ranges for T1 and T2 are shown in Table .2% myocaFor both sexes, linear regression showed that no correlation between age, BMI, and global T1 or T2. In males, a positive correlation was found between HR and global T1 , but not for global T2. In females, no correlation was found between HR and global T1 or global T2.Segmental T1 and T2 values according to the AHA 16-segment model are shown in the bulls-eye plots in Fig. The intra-observer and inter-observer variabilities of the T1 and T2 values are shown in Table In this large multicenter 3T CMR study, using a standardized scanning platform and protocol, as well unified post-processing in a core laboratory, reference ranges for myocardial T1 and T2 relaxation times were established. The reference ranges show discrepancies with previous 3T single center studies. Although no significant correlations were found between age, sex, and myocardial T1 or T2 values, sex and age differences are confirmed. In addition, phantom analysis demonstrates the transferability of the T1 and T2 mapping protocols beyond a single site, which provides a viable basis for multicenter CMR studies in heart disease utilizing mapping techniques.Currently, the most widely used clinical techniques for T1 mapping are based on the MOLLI or shortened-MOLLI (shMOLLI) techniques . MyocardPrevious studies have reported conflicting information on age or sex associations of myocardial T1 values , 23, 24.Myocardial T2 relaxation curves are constructed based on the multi-echo pulse sequences, and the most frequently used techniques are T2p-bSSFP and gradient spin echo (GRASE) supplied by different vendors. Myocardial T2 reference values reported in previous studies were significantly different, ranging from 32 to 47 ms  –29 at 3TWe observed slightly higher T1 and T2 values in the apex than in the basal and mid myocardium. Partial volume effect due to the LV curvature could explain this finding by including the blood signal into voxels . We atteWe found myocardial T1 and T2 relaxation times were longer in females than in males, which is consistent to previous 1.5T studies , 32. HowThe CMR core laboratory can provide a platform for image quality control and accurate image analysis in multicenter studies. The SD of global T1 values (34 ms) in this study was close to or smaller than previously reported single-center studies , rangingThe present study has several limitations. The reference range in the present study provided only a reference for the same field strength and vendor. Contrast-enhanced imaging was not performed on healthy subjects, so we did not obtain reference ranges for post-contrast T1 and ECV, and subclinical disease or remote myocardial injury may have confounded results. The study only concerned subjects of Chinese ethnicity and did not involve direct comparisons between ethnicities. In addition, hormone levels and other serum biomarkers were not available. Correlations between native T1 and T2 and biomarkers need further exploration.In summary, using phantom-validated protocols, we systematically provide 3T reference ranges for myocardial T1 and T2 relaxation times derived from a large multicenter study of healthy Chinese adults. Myocardial T1 and T2 relaxation times were longer in females than in males. There were statistical differences in T2 across age groups, but not in T1. Our study further suggests that sex and age should be considered when interpreting myocardial T1 and T2 results. After controlling for demographic-related factors and technical heterogeneity, the present study can be referenced for the diagnosis, risk stratification, and prognostic analysis of native tissue characteristics in Chinese subjects in clinical practice and research at 3T.Additional file 1: Table S1. Parameters of T1 and T2 mapping by age decades for men. Table S2. Parameters of T1 and T2 mapping by age decades for women.


Six weeks after discharge, the iron status of the MCD patients was already comparable to that of the control group. During hospitalization, lower serum iron and TSAT correlated with higher NT-proBNP (both p < 0.05). In-hospital lower serum iron and TSAT correlated with both a lower left ventricular ejection fraction (LVEF) and worse left ventricular global longitudinal strain at follow-up visits . In conclusion, in patients with acute MCD, iron status is altered and normalizes within six weeks. Low serum iron and TSAT are related to greater in-hospital neurohormonal activation and subtle persistent left ventricular dysfunction.Pathomechanisms responsible for recovery from acute myocarditis (MCD) or progression to non-ischemic cardiomyopathy have not been comprehensively investigated. Iron, positioned at the crossroads of inflammation and the energy metabolism of cardiomyocytes, may contribute to the pathophysiology of inflammatory myocardial disease. The aim of this study was to evaluate whether systemic iron parameters are related to myocardial dysfunction in MCD patients. We prospectively enrolled 42 consecutive patients hospitalized for MCD. Their iron status and their clinical, laboratory, and echocardiographic indices were assessed during hospitalization and during ambulatory visits six weeks after discharge. A control group comprising healthy volunteers was recruited. The MCD patients had higher serum ferritin and hepcidin and lower serum iron concentration and transferrin saturation (TSAT) than the healthy controls (all  In the majority of patients with acute myocarditis (MCD), the disease spontaneously regresses without significant clinical sequelae ,2,3. HowThere are pathophysiological links between disordered iron status and cardiomyopathy. Both iron deficiency and iron overload are detrimental for cardiomyocytes. This provides an insight into the U-shaped relationship between a (sub-)cellular iron level and cardiomyocyte homeostasis ,13,14,15The aim of the current study was to evaluate whether systemic iron parameters are related to myocardial dysfunction in acute MCD patients.The prospective MCD registry consisted of patients who were hospitalized consecutively for acute MCD during 2014–2019 in two tertiary referral cardiology centers: the Cardiology Department of the Center for Heart Diseases in the 4th Military Hospital in Wroclaw and the Department of Cardiology of the Tadeusz Marciniak Lower Silesia Specialist Hospital—Emergency Medicine Center in Wroclaw.MCD was diagnosed according to the criteria presented in The study protocol was approved by the local ethics committee . All patients provided written informed consent to participate in the study. The study was conducted in accordance with the Declaration of Helsinki.During their hospitalization for acute MCD, the patients were assessed at the emergency department and 3 ± 1 days after admission to the cardiology department. A control ambulatory visit was scheduled 6 ± 1 weeks after discharge. The study design scheme is presented in The demographic and anthropometric characteristics, medical history, comorbidities, and the characteristics of clinical presentation  of acute MCD were collected at the cardiology department . At each timepoint , assessment of the vital signs and physical examination were performed. Mean systolic blood pressure, mean diastolic blood pressure, and mean heart rate were calculated as an average from 3 consecutive measurements.We analyzed the following emergency department laboratory tests: serum hemoglobin, white blood cell count, high-sensitivity cardiac troponin I (hs-cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), serum creatinine, and alanine transaminase (ALT). The following basic laboratory parameters were measured - in fresh venous blood: in patients with acute MCD at the cardiology department and during ambulatory visit: serum hemoglobin, red blood/white blood cell/neutrophil/lymphocyte/monocyte count, reticulocyte hemoglobin content, reticulocyte count, hs-cTnI, NT-proBNP, CRP, ALT, serum creatinine, serum insulin, and thyroid-stimulating hormone.The following blood biomarkers/parameters, reflecting iron metabolism, were measured directly (from fresh venous blood): serum ferritin (μg/L)—with an immunoassay based on electrochemiluminescence with the Elecsys 2010 System ; iron (μg/dL); and unsaturated iron-binding capacity - based on a substrate method with Feren S . The total iron-binding capacity (μg/dL) was automatically calculated using serum iron and unsaturated iron-binding capacity. Transferrin saturation (TSAT) was calculated as the ratio of serum iron (μg/dL) and total iron-binding capacity (μg/dL), and expressed as a percentage. Soluble Transferrin Receptor  and hepcidin (ng/mL) were measured in frozen sera, after obtaining and preparing biological material from all study enrollees. Clotted blood samples were centrifuged and the supernatants were collected and frozen in −80 °C for further analysis. STfR was measured using immunonephelometry . Hepcidin was assessed using a commercially available, enzyme-linked immunosorbent assay  for detecting human hepcidin-25, dedicated for research use only. This is a unique hepcidin ELISA kit which has been validated with a gold standard for hepcidin assessment—liquid chromatography mass spectrometry (LC MS) . For accA standard transthoracic echocardiography was performed at the cardiology department and during ambulatory visit six weeks after discharge. For the purposes of this study, the following variables were analyzed: left ventricular ejection fraction (LVEF), estimated using Simpson’s planimetric method; left ventricular global longitudinal strain (LV GLS), measured by the speckle tracking technique; indices of left ventricular diastolic function , assessed with the use of continuous wave and tissue doppler imaging; tricuspid annular plane systolic excursion (TAPSE) and segmental myocardial contractility dysfunction, estimated visually by an experienced sonographer.−coronary angiography or coronary computed tomographic angiography—to exclude obstructive coronary artery disease; −cardiac magnetic resonance—in search for the indices of MCD, to confirm the diagnosis.We analyzed the following other diagnostic procedures, performed during the index hospitalization in the cardiology ward:t-test for unpaired samples. The categorical variables were expressed as numbers (with percentages). The intergroup differences regarding the categorized variables were tested using the Pearson’s Chi-square test. The associations between the iron status indices and the laboratory or echocardiographic parameters were tested using Pearson’s correlation coefficients. The changes in laboratory parameters between the hospitalization and the ambulatory visit were tested using t-test for paired samples. A value of p < 0.05 was considered statistically significant. All statistical analyses were performed using the Statistica 13 data analysis software system .Most of the continuous variables had a normal distribution, and were expressed as mean (standard error of the mean). NT-proBNP, hs-cTnI, CRP, serum hepcidin, reticulocyte count, ALT, alcohol consumption, and neutrophil-to-lymphocyte ratio had a skewed distribution and were expressed as median with lower and upper quartiles (interquartile range). These variables were log-transformed  before inclusion in further analyses. The intergroup differences between the patients with acute MCD and the healthy controls were tested using the −3 with normal level of high sensitivity cardiac troponin I;−18 without indices of MCD in cardiac magnetic resonance.Out of 63 patients admitted to the hospital with suspected acute MCD, 21 initially evaluated subjects were excluded:The final study group of patients hospitalized for acute MCD comprised 42 subjects.The baseline demographic, clinical, laboratory, and echocardiographic characteristics of the study group versus controls, who were 15 age-matched and gender-matched healthy volunteers, are presented in The most prevalent symptoms of acute MCD were chest pain—in 39 (93%) patients, dyspnea—in 13 (31%), and palpitations—in 6 (14%). Two (5%) patients presented symptoms of acute heart failure at the time of admission. Within 30 days before admission to the hospital, fever (T > 38 °C) was present in 26 (62%) of the patients, pharyngitis in 25 (60%), arthritis in 22 (52%), cough in 18 (43%), rhinitis in 15 (36%), nausea/vomiting in 10 (24%), stomach pain in 4 (10%), diarrhea in 3 (7%), and sinusitis, rash, and dysuria in two (5%) patients. Twenty-two (52%) subjects still presented symptoms of infection at the time of admission.In transthoracic echocardiography, the patients hospitalized for acute MCD presented lower LVEF, higher LV GLS, and worse parameters of diastolic function—lower values of E/A, e’ lat and higher of E/e’—compared to the control group . A segmeThe ambulatory visit at six weeks after discharge was missed by 7 patients—data for 35 subjects were available. No differences regarding baseline clinical characteristics were found between the 35 patients, who attended the ambulatory visit, and the 7 patients, who were lost to follow-up.p-values < 0.001), and already comparable to the healthy controls . The changes in the indices of iron status after six weeks of recovery together with the comparison to the control group are presented in At the ambulatory visit, NT-proBNP, high-sensitivity troponin I, and CRP were lower than during the hospitalization  correlated with CRP. Lower in-hospital serum iron and TSAT were associated with higher in-hospital NT-proBNP.Moreover, an analysis of echocardiographic evaluation, performed six weeks after discharge, demonstrated that lower serum iron and TSAT, measured during the hospitalization, were associated with a persistent left ventricular dysfunction (lower LVEF and higher LV GLS) at the follow-up visit .The levels of hs-TnI, NT-proBNP, LVEF and LV GLS, assessed during the follow-up visit, were neither related to CRP, nor to white blood cell indices  from the index hospitalization.The major findings arising from the current study are (1) the patients with acute MCD had comparable red blood cell indices but altered indices of iron status, compared with the healthy controls, (2) disordered iron parameters normalized within six weeks after the index hospitalization, (3) low serum iron and TSAT, which constitute indices of iron deficiency but not acute phase reactants, were correlated with greater in-hospital neurohormonal activation (measured via the concentration of natriuretic peptides), together with a subtle persistent left ventricular dysfunction, detected after six weeks of recovery (assessed via LVEF and LV GLS).There is evidence, from experimental animal and cell cultures, that systemic iron deficiency relates to multifaceted myocardial dysfunction ,10,12,18Although we have no data on the cardiomyocyte iron status in patients with acute MCD, there have been documented links between the systemic iron status and myocardial iron metabolism ,40,41. CFurthermore, relationships between iron deficiency and an impairment of antioxidative defense have been postulated . Iron coIron metabolism plays an important role in the pathogenesis of inflammation . Both feOur study has demonstrated an association of lower serum iron and TSAT with greater in-hospital neurohormonal activation and with a subtle deterioration of left ventricular function after six weeks of observation. Considering the aforementioned mechanisms of the pathophysiology of inflammation, our finding may be explained by the fact that the decrease in TSAT and in serum iron concentration may reflect an enhanced myocardial inflammation and a more extensive affection of the myocardium. Furthermore, functional iron deficiency, expressed by low TSAT, can derange myocardial energetics. In consequence, it may adversely affect the processes of healing the damaged myocardial tissue, and thus impair recovery from acute MCD. What is of note, CRP—a biomarker of inflammation routinely used in clinical practice—was related neither to the in-hospital neurohormonal activation nor to the subtle persistent left ventricular dysfunction. The reason for the difference between CRP and TSAT, or serum iron concentration, may be the fact that, in contrast to CRP, the analyzed iron parameters express cumulatively both the intensity of the inflammation and the disturbed myocardial energetics, and thus, they better manifest the defected recovery process. These indices of iron status may reflect multiple negative mechanisms during the recovery, not only those concerning the inflammatory response.Further studies and longer periods of observation are required to determine the relationships between the iron metabolism during acute MCD and the risk of an unfavorable progression to post-myocarditis non-ischemic cardiomyopathy. However, the assessment of circulating biomarkers of iron status may become a valuable tool in risk stratification and the evaluation of recovery after acute MCD. Moreover, the treatment of iron deficiency in MCD patients could constitute an interesting area for the future clinical trials.The current study has certain limitations, which should be punctuated. Firstly, although the recruitment was conducted in two cardiology centers, and consecutive patients hospitalized for acute MCD were enrolled, the final study group comprised a relatively small number of subjects, and thus only basic statistical analyses were performed. However, it needs to be acknowledged that the previous research into MCD has mainly comprised studies of small-scale populations, above all, due to the relatively low incidence of this disease. Therefore, extensive multicenter trials in larger populations are greatly needed. Secondly, we assessed indices of peripheral blood iron status, and we have no data on the myocardial iron status, which may be crucial for a better recognition of the role of iron in the pathobiology of myocardial inflammation. Eventually, to evaluate the inflammatory reactions, we utilized only C-reactive protein concentrations, while a complex assessment of inflammatory indices, including concentrations of pro-inflammatory interleukins, would give a superior insight into the contribution of the immune response, its relationships with iron metabolism, and its associations with recovery from acute MCD.Patients hospitalized for acute MCD have comparable red blood cell indices, but altered indices of iron status, compared with healthy controls. The deranged iron status normalizes within six weeks of recovery. Lower serum iron and TSAT (indicators of iron deficiency other than acute phase reactants) correlate with a greater in-hospital neurohormonal activation and a subtle persistent left ventricular dysfunction.


Already, a first human study has used antibodies to modulate specific signaling pathways of the innate immune system in the CANTOS trial.3 The results showed a reduction in the primary endpoints, including non-fatal or fatal myocardial infarction and stroke. However, the results also demark the challenge to identify the patients who benefit the most from a therapy connected with high costs and risks due to manufactured immunosuppression.4Acute ischemia has an immense impact on the cellular and structural integrity of the myocardium. It triggers an inflammatory response that is a vital factor for the further clinical and prognostic outcome.5Therapeutic approach like CANTOS make use of knowledge obtained from in vitro and animal experiments. These experiments demonstrate the impact of macrophages and lymphocytes on myocardial healing and remodeling and also play a role in the development of complications such as an increasing incidence of ventricular thrombi when the monocyte/macrophage function is impaired.6However, the transfer from bench to bedside remains a challenge. In patients with acute myocardial infarction, the clinical presentation is by far more complex and variable than a precisely defined experiment can reproduce. Histological prove of myocardial cell infiltration is hardly obtainable and quantification of the inflammatory process itself is limited to parameters derived from peripheral blood samples.7 Cardiac MRI adds the unique information of changes in the extracellular volume such as edema and necrotic tissue in the acute setting. In the chronic stage after myocardial infarction, it detects the scar tissue as result of the post-infarction inflammation and remodeling. Thus, it is used in clinical trials for the outcome assessment.8Established clinical imaging methods allow a detailed analysis of the immediate and long-term effects of inflammation on the myocardium. Echocardiography is a readily available and fast tool for detection of myocardial function, wall motion, and pericardial effusion. It is a valuable tool for early risk stratification after myocardial infarction and offers profound insight into both systolic and diastolic functions.However, these imaging techniques examine the effects of inflammation on the myocardial damage, but do not elucidate the process of inflammation itself. For this purpose, nuclear medicine is the imaging modality to turn to.9Among the tracers used routinely for oncologic indications, SSTR2-targeted tracers has proven its potential for translation into detection of inflammation. SSTR2-targeted PET is used to detect neuroendocrine tumors that show a significant upregulation of SSTR2 expression. This is useful not only for the detection and monitoring of tumor disease but also for therapeutic interventions.10 Besides detection of SSTR2-targeted tracer uptake in large vessels, other works were able to discriminate between high-risk and low-risk lesions in carotid and coronary vessels.11Besides neuroendocrine tumorous tissues, a variety of cell groups expresses SSTR2. Among these, macrophages are especially noteworthy as they are key to open the door of translation. PET has a whole body or at least thoracic read out, and as such, offers information on other not primarily targeted tissues and organs. Earlier works successfully used SSTR2-targeted imaging in oncologic patients in order to detect inflammation in atherosclerotic plaques of larger arteries and to connect the imaging findings to cardiovascular risk factors.12From these large-vessel analyses, the next step toward for direct visualization of myocardial inflammation was pursued in smaller pilot series and studies that focused on myocardial inflammation either with inflammatory diseases or after myocardial infarction. Among others, a small pilot series examined patients either with acute myocardial infarction or acute myocarditis with cardiac MRI and SSTR2-targeted PET/CT. Results showed a good concordance between MRI findings indicating acute myocardial damage and tracer uptake.13 Most recently, first data from an ongoing prospective study further supports the potential for detection of prolonged macrophage activity months after the initial acute event.14Tarkin et al. were able to show [68Ga]Ga-DOTATATE uptake not only in patients immediately after acute myocardial infarction but also in patients with chronic ischemic heart disease.15 In a very first case report 2022, a first experience with the detection of myocardial inflammation after acute anterior wall infarction was presented.16 Similar to the experiences with SSTR2-targeted PET, this patient showed tracer uptake in the myocardial segments matching the findings from cardiac MRI. Following this very first proof of principle, Sazonova et al. now present a further look at this imaging approach.17 They focused on using [99m]Tc-Tektrotyd scintigraphy in order to detect the myocardial changes caused by myocardial infarction over a time period of 6 months. Similar to previous endeavors, the case number is small but includes a well-defined homogeneous group of patients and a multimodal and serial imaging approach is chosen for characterization of the acute and chronic changes within the myocardium. Within the small patient group, the authors were able to link the [99m]Tc-Tektrotyd uptake to the extent of myocardial damage immediately after the acute event and to significantly predict changes in the end-diastolic volume after six months. With these findings, the authors fall in line with previous SSTR-targeted imaging works. However, follow-up information with the help of repeated myocardial scans with nuclear medicine techniques are rare. Sazonova et al. add to the available data with their follow-up study. Interestingly, even in this small and homogeneous group of patients, the tracer uptake at the follow-up time point shows quite a variation in results. Based on 11 patients, conclusions regarding the clinical interpretation should be drawn carefully as each sub-group consists of only few patients. Nevertheless, these few data hint at individual inflammatory responses, highlighting the need for imaging techniques that predict and detect these individual inflammatory responses.Regardless of these promising results, we still have not established one routinely used technique for direct visualization of myocardial inflammation. One the one hand, not all techniques are readily available at all departments, both from a technical and from a financial point of view. On the other hand, there are a lot more to establishing a routine application than the proof of principle. Regarding the first obstacle, the availability of imaging methods, [99m]Tc-Tektrotyd scintigraphy might prove a valuable addition to the portfolio of potential targeted imaging approaches. [99m]Tc-Tektrotyd has been established as alternative for detection of somatostatin receptor expression on tumorous tissues.Small-sized cases series and pilot studies such as the presented are a valuable and necessary step for transferring the principle of targeted imaging from oncology to cardiology. Following these works of proof of principle, the next challenge is to transfer the results into a wider application and to win over the clinical teams to use these imaging techniques. As a foundation, careful interpretation of technical aspects and analysis of potential pitfalls have to serve as advocates for credibility and applicability.18 Earlier studies with SSTR-targeted PET/CT showed that there is a strong tracer uptake in the liver. This might influence the sensitivity for inflammation in the inferior myocardial wall.12The target lesions often are delicate, such as atherosclerotic plaques. These lesions easily have dimensions less than 5 mm. Systematic analysis of tracer uptake and confounding factors are necessary to validate a relevant tracer uptake from potential image noise and to prevent misleading correlations with clinical markers. Furthermore, knowledge of physiological tracer uptake of different organs has to be obtained. However, true healthy reference cohorts are not available due to the exposure to ionizing radiation during the imaging procedure. Therefore, physiological distribution of SSTR2-targeted tracer uptake has been described in patients with suspicion of malign diseases but with non-pathological scans.5 This leaves the question, whether by choosing the timing of the imaging procedure, different aspects of the inflammatory response are detected. In the studies so far, a timeframe from 2 to 11 days after the acute event were covered.16 As of yet, the data are too few to draw definitive conclusions, but this open question will have to be addressed in future.Last but not least, the optimal timing for direct visualization of inflammation has yet to be determined. We know that cell activation after acute myocardial infarction follows a complex time line with different macrophage subtypes being activated at different time points.In conclusion, studies like the presented are a vital step to push existing imaging techniques into new fields of applications. In doing so, a valuable key to the direct visualization of inflammation can be obtained. Nevertheless, following this first success, further challenges such as technical considerations and clinical interpretation of obtained data will have to be overcome in order to establish a routinely used application of SSTR2-targeted imaging. Once achieved, it promises to be the tool to identify patients who will benefit from targeted therapies proposed in trials, such as CANTOS.


Background: Cardiovascular diseases (CVDs) are a global concern. CVD remains a primary cause of death despite reduced coronary heart disease death rates. Acute coronary syndrome (ACS) involves myocardial infarction (MI) and unstable angina, sharing mechanisms such as plaque instability. Our study assesses the right ventricular (RV) function's predictive value in acute inferior wall MI (IWMI) to identify high-risk patients with an elevated likelihood of experiencing severe cardiac complications, hemodynamic instability, or a higher mortality risk following an acute IWMI.Methodology: The research was conducted in the Department of Cardiology at the Rajendra Institute of Medical Sciences (RIMS), Ranchi, from July 2021 to June 2022, following the necessary ethical approval. A cohort of 140 patients with IWMI, carefully chosen according to rigorous criteria, clearly understood the study's objectives before providing informed consent. The evaluations were conducted in the following order: clinical assessments, followed by blood testing, then echocardiography, and finally, coronary angiography. Furthermore, the study examined risk factors and utilized statistical methods to elucidate the associations between qualities and results.Results: The study included 140 participants, with 61% being male and 39% female. Among the participants, 14% were aged 30-45, 50% were aged 46-60, and 30% were over 60. Age shows significant proportions in different categories. Diabetes, dyslipidemia, hypertension, and smoking/tobacco addiction did not differ among stenosis groups. Proximal right coronary artery (RCA) stenosis patients had elevated jugular venous pressure (JVP). The echocardiograms were performed within 48 hours of post-percutaneous coronary intervention, and significant differences between groups were observed. Participants with proximal stenosis had lower tricuspid annular plane systolic excursion (TAPSE) and right ventricular fractional area change (RVFAC), which showed compromised RV systolic function. Proximal stenosis patients had reduced systolic motion velocity (Sm), indicating impaired myocardial contraction. Echocardiographic parameters such as early diastolic velocity (Em), atrial contraction velocity (Am), Em/Am ratio (a marker of diastolic function), isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET) between groups were different, indicating distinct cardiac functions. Proximal stenosis increased the myocardial performance index (MPI), indicating cardiac impairment. The left ventricular ejection fraction (LVEF) was comparable in the two stenosis groups, indicating similar left ventricular performance.Conclusion: Echocardiography showed significant RV function differences in acute inferior wall ST-segment elevation myocardial infarction (STEMI) patients with proximal and distal RCA lesions. RV dysfunction is linked to right ventricle myocardial infarction (RVMI), and echocardiographic markers can provide valuable insights. Results emphasize that acute inferior wall STEMI is diagnosed by electrocardiogram (ECG) criteria, particularly ST-segment elevation. However, these markers emphasize the importance of RV assessment in RCA involvement assessment. These findings suggest that RV function can help diagnose acute inferior wall STEMI RCA involvement. In acute inferior STEMIs, RV function echocardiography is essential for RCA lesion location. Cardiovascular disease (CVD) is a significant problem in developed countries and is growing in developing countries . Over thMIs of the left ventricle (LV) have received considerable attention, but the effects of the right ventricle (RV) MIs on patients were not fully understood until 1974. In clinical practice, the heart's right ventricle (RV) is almost always supplied with blood by the right coronary artery (RCA), regardless of coronary artery dominance . This geElectrocardiograms (ECGs) are crucial in diagnosing heart attacks by detecting specific changes in the heart's electrical activity, helping assess myocardial damage . In 48% Ethical approval and study designThe Rajendra Institute of Medical Sciences (RIMS), Ranchi, Jharkhand, Institutional Ethics Committee granted their approval for this study under memo number 250IEC, RIMS . Ethical guidelines were strictly followed in our study to ensure accuracy and reliability. Participants fully understood the study's goals before giving informed consent to participate.Patient selectionThe research was carried out at a teaching hospital in Ranchi, Jharkhand, between July 2021 and June 2022. It comprised 200 patients who were admitted to the coronary care unit within 24 hours of experiencing their first symptoms of acute inferior MI. Patients in the study were diagnosed with acute inferior MI based on a clinical evaluation, the patient's medical history, and ECG results, particularly an increase in the ST segment in the inferior leads . A total of 140 patients were selected for the study after a rigorous selection procedure based on predetermined criteria including age, gender, medical history, and clinical symptoms.Subject selectionInclusion CriteriaPatients were included if they had an acute inferior MI, at least 30 minutes of chest pain, and an ECG with an ST-segment elevation of ≥0.2 mV in the inferior leads. An additional inclusion criterion was the presence of a right ventricle myocardial infarction (RVMI) associated with an inferior MI, which was defined by an ST-segment elevation of ≥0.1 mV in V4 through V6R lead. Participants had to have a favorable echocardiographic window for a precise evaluation. In addition, coronary angiography confirmation of significant stenosis in the RCA was an essential inclusion criterion.Exclusion CriteriaThe study did not include patients who were in critical condition or hemodynamically unstable and required immediate primary percutaneous coronary intervention (PCI). Additionally, individuals with significant lesions in the left anterior descending coronary artery, diffuse lesions in the RCA, or multivessel disease were excluded. Those with suboptimal echocardiographic views that hindered accurate assessments were also not considered for this study. Patients with a history of cor pulmonale, MI, atrial fibrillation, or significant valvular heart disease were likewise excluded from the study. We excluded patients with specific ECG patterns, bundle branch blocks, and conditions that can change ECG readings, such as pericarditis, myocarditis, and electrolyte imbalances. The presence or absence of these conditions was assessed through a combination of clinical evaluation, patient history, and diagnostic tests such as echocardiography, cardiac enzymes, and blood electrolyte levels. Finally, the study excluded patients whose culprit lesion was not identified during coronary angiography. The angiography results divided the patients who met these criteria into two groups: 58 with distal RCA stenosis  and 82 with proximal stenosis .Clinical evaluation and laboratory testsClinical evaluations were performed precisely to identify signs of RV failure (RVF), such as hypotension and an increase in jugular venous pressure (JVP), particularly when there were clear lung fields present. Blood samples were taken for laboratory testing to determine the total blood count, lipid profile , and random blood sugar. Additionally, troponin T was measured, serving as an essential biomarker for assessing myocardial damage.Conventional echocardiographic examinationFollowing initial stabilization and within the first 48 hours post-infarction, all patients underwent a comprehensive conventional echocardiographic evaluation using the General Electric (GE) HealthCare VividTM E95 echocardiographic system . This system had a flexible 1-5 MHz transducer and a tissue-specific Doppler imaging mode. Standard views recommended by the American Society of Echocardiography (ASE) were utilized during the examination. The peak tricuspid regurgitation (TR) jet velocity and the simplified Bernoulli equation were used to determine the RV systolic pressure (RVSP). This data was then combined with an estimate of right atrial (RA) based on the inferior vena cava diameter and respiratory variations. The RV's end-diastolic dimensions were measured using a four-chamber apical view centered on the RV. This view enabled the measurement of the RV's maximum diameter while also encompassing the heart's apex and crux.RV function parametersThe measurement of tricuspid annular plane systolic excursion (TAPSE) was obtained by positioning an M-mode cursor across the tricuspid lateral annulus in an apical four-chamber view. The purpose was to quantify the longitudinal displacement of the annulus during peak systole. The pulsed-tissue Doppler imaging technique was utilized to evaluate cardiac dynamics. The images were captured through the apical four-chamber window, utilizing the tissue Doppler mode and focusing on the RV-free wall. At the end of expiration, the pulsed Doppler sample volume was placed at the tricuspid annulus of the basal RV free wall segment to minimize translational motion.Comprehensive velocity profiles spanning the entire cardiac cycle were generated using the specific software, revealing distinct peaks and troughs. These included a significant positive peak systolic velocity (Sm), which indicated that the annulus was moving toward the apex during systole. In addition, negative early diastolic myocardial velocity (Em) measurements were recorded as the annulus ascended away from the apex. Following that, negative late diastolic myocardial velocity (Am) readings were recorded. The dynamic behavior of Sm, Em, and Am waves was effectively characterized by this analysis. Critical time intervals were meticulously measured to probe deeper into cardiac performance. The duration of Sm was calculated using the ejection time (ET). Isovolumic relaxation time (IVRT) data was obtained by calculating the time elapsed between the end of Sm and the start of Em. The duration of the interval between the end of Am and the beginning of Sm also provided insight into the isovolumic contraction time (IVCT).The myocardial performance index (MPI), a key indicator of cardiac function, was calculated using the following formula: MPI = [(IVRT + IVCT) / ET].Coronary angiographyCoronary angiography was performed within the initial week following MI to pinpoint the culprit lesion. This procedure involved the utilization of a Judkins catheter, following standardized techniques. The presence of total or subtotal occlusion of the coronary artery supplying the asynergic field was a crucial criterion for identifying the culprit lesion. Arteriography reveals that these characteristics frequently result from acute thrombosis or dissected plaque. This rigorous approach ensured the accurate definition of the culprit lesion. Based on the anatomical position of the RCA lesion in relation to the origin of the RV branch, the patients were divided into two different groups: group 1 included patients with the culprit lesion in close proximity to the RV branch of the RCA, and group 2 included patients with the culprit lesion far from the RV branch of the RCA.Statistical analysisSTATA 11.0  was used for descriptive statistics. To compare continuous variables, the Student t-test or Mann-Whitney test (depending on the data distribution) was utilized, whereas the Chi-square test was utilized for categorical variables. Multiple regression analyses determined the best RV function parameters for proximal RCA ischemia prediction . A receiver operator characteristic curve modeled the most independent proximal RCA lesion predictors. Youden's equation found the best parameter cutoff for sensitivity and specificity. Echocardiographic features associated with angiographic RCA stenosis were recorded, analyzed, and concluded.The study population was separated into two categories based on gender: males and females. Out of a total of 140 participants, 86 (61%) were males, while 54 39%) were females Table . Of this9% were fDelving further into the male population with proximal RCA stenosis (52 patients), the age distribution revealed that 10 (19%) individuals were within the age group of 30-45 years, and 18 (34.6%) patients fell between the ages of 46 and 60 years. The remaining 24 (46%) patients were aged above 60 years  and diastolic BP were 118 ± 18.6 and 79 ± 9.6 mmHg, respectively Table , and theThis study examined echocardiographic variables to compare proximal and distal RCA stenosis patients. TAPSE stands out with a value of 12.7 ± 1.4 and 18.3 ± 2.4 in the proximal RCA stenosis group and the distal RCA stenosis group, respectively, with a significant difference (p ≤ 0.05) Table . The rigThe Sm was significantly lower in the proximal RCA stenosis group 11.5 ± 2.6 cm/s) compared to the distal group (15.4 ± 3.0 cm/s), with a p-value of ≤0.0001  longer IVRT (109 ± 18 ms) than the distal group (85 ± 18 ms), indicating delayed relaxation. The IVCT showed no significant difference between groups. The proximal RCA stenosis group had an IVCT of 80 ± 14.4 ms, while the distal group had 74 ± 19 ms Table . The ET Accurate identification of the culprit artery is critical in the risk stratification and optimization of treatment approaches for patients afflicted by acute IWMI. Particularly, the mortality rate for acute IWMI cases accompanied by RV involvement attributable to proximal lesions within the RCA is notably elevated at 16%, in stark contrast to the 3.5% mortality rate observed in cases of isolated acute IWMI . ECG assOur study reported that of the total study population of 140 patients, 58.5% had proximal RCA stenosis and 41.5% had distal RCA stenosis. This distribution contrasts with Rajesh et al. , who preRajesh et al.  found thIn the current study, a 10-fold increase in elevated JVP was observed in proximal RCA stenosis compared to distal RCA stenosis, which was clinically significant. This finding suggests a potential association between proximal RCA stenosis and increased JVP, which may reflect RV function and hemodynamics variations. Further investigation into this observation's underlying mechanisms and clinical implications is required to better comprehend its implications for patient management and risk evaluation. There was no significant difference in thrombolysis rates between the proximal and distal RCA stenosis groups in the current study, implying that the decision to administer thrombolytic therapy was unaffected by the location of the RCA stenosis. The lack of a significant difference in thrombolysis rates between patients with proximal and distal RCA stenosis may reflect healthcare professionals' clinical judgment to provide appropriate treatment regardless of the anatomical location of the stenosis. However, the decision to use thrombolytic therapy in any STEMI presentation, irrespective of location, should be based on clinical assessment and guideline adherence, especially when PCI is delayed. It is important to remember that the decision to undergo thrombolysis was most likely influenced by several factors, including the severity of symptoms, the extent of ischemia, the patient's overall condition, and the length of time since symptoms first appeared.In our study, TAPSE was found to be lower in patients with proximal RCA stenosis than those with distal RCA stenosis, which was statistically significant (p ≤ 0.05). Previous research has found a strong link between TAPSE and ECG evidence of RVMI . FurtherOur 2D echo analysis showed that patients with proximal and distal RCA stenosis had statistically significant (p < 0.05) differences in RVFAC. RVFAC, an indicator of RV systolic function, was lower in patients with proximal RCA stenosis. This highlights its potential as an indicator of myocardial impact localization. FAC, which measures the overall systolic function of the RV, correlates with cardiac magnetic resonance imaging (MRI)-measured RV ejection fraction . In addiWe found a statistically significant difference (p < 0.0001) in Sm between patients with proximal RCA stenosis and distal RCA lesions. Ozdemir et al.  supporteEarly filling immediately tracks the end of the systolic motion in a normal RV with intact contractility and normal loading conditions, and the RV IVRT needs to be more brief and present. Consequently, a detectable IVRT indicates elevated RV end-systolic pressure . In our LimitationsSeveral limitations were acknowledged when interpreting the study's findings. An echocardiographic evaluation should precede any reperfusion strategy to account for the possible recovery of RV function. Ethical considerations precluded delaying reperfusion to perform an echocardiographic evaluation. In addition, there is a possibility that later coronary angiograms missed cases of spontaneously reopened proximal RCA occlusions. In addition, it is important to note that a proximal RCA lesion does not necessarily indicate RV myocardial involvement, even though it is recognized as an independent prognostic indicator in acute inferior wall IWMI cases.In summary, the comprehensive echocardiographic evaluation of diverse parameters relating to RV function in the context of acute inferior wall STEMI has revealed substantial differences between groups characterized by proximal and distal RCA lesions. Among 140 participants, mostly males (61%) aged above 45 years, key findings emerged. The utility of easily accessible measures such as tissue Doppler systolic annular velocity, MPI, and TAPSE has been underscored in predicting the proximal RCA as the infarct-related artery. It is noteworthy that all patients diagnosed with proximal RCA stenosis exhibited RV dysfunction upon echocardiographic analysis. Importantly, the study's findings also emphasize a high incidence of RVMI in patients with proximal RCA stenosis, reinforcing the clinical significance of these observations.


This study aimed to assess left heart remodelling changes in hypertension, excluding underlying ischaemic heart disease, utilising computed tomography coronary angiography (CTCA) and transthoracic echocardiography (TTE).n = 96, Group 1), and Group 2 served as age-matched controls . All participants underwent both CTCA and TTE. TTE measurements included left ventricle (LV) concentricity and function and left atrial (LA) volume and function. Using both CTCA and TTE, we measured LV diastasis volume (LVdias) and LA diastasis volume (LAdias).A total of 178 patients  were enrolled in the study: Group 1 consisted of patients with essential hypertension  index to mean wall thickness . Group 1 showed higher LAdias and LA minimal volumes, while LA reservoir function was lower in Group 2. The LVdias/LAdias ratio was lower in Group 1 compared to Group 2 . A composite score based on four combined TTE parameters, namely, LVED index/mean wall thickness ≤57, ratio of early diastolic mitral inflow to mitral annular tissue velocities (E/e’) >8, LVdias/LAdias ≤1.62, and LA reservoir function ≤0.58, yielded the highest discriminatory power (area under the curve—AUC = 0.772) for distinguishing patients with hypertensive heart disease (HHD). Collectively, we refer to these parameters as the LEDA score, with each parameter scored as one point. For LEDA scores of 0, 1, 2, 3, 4, the probability of underlying HHD was 0%, 23%, 59%, 80%, and 95%, respectively. Furthermore, a CTCA-derived LVdias/LAdias ≤1.76, considered as a single parameter, demonstrated modest accuracy in differentiating patients with HHD (AUC = 0.646).LV mass index and LV mass/heightED index/mean wall thickness, E/e’, LVdias/LAdias, and LA reservoir function, proved to be the most effective in defining left heart remodelling in hypertension.The TTE LEDA score, based on four parameters, namely, LV  While there have been significant global improvements in the treatment and control of hypertension, there remains a critical need for more timely detection of this condition. This is because the cumulative effects of hypertension can ultimately lead to cardiac overload, remodelling, and heart failure (HF) –3. It isn = 96) and Group 2 contains an age-matched control group that included patients who had no clinical evidence of hypertension or diabetes (n = 82). Hypertension was diagnosed according to the European Society of Cardiology guidelines  sinus rhythm, (2) absence of valvopathy ≥2/4 and/or cardiomyopathy, and (3) CTCA and TTE of diagnostic image quality. Patients with documented myocardial ischaemia and/or history of myocardial infarction or coronary artery revascularisation were excluded. The initial group consisted of 229 patients, with 51 patients excluded for the following reasons: nine of 51 patients were excluded because of subsequently documented myocardial ischaemia requiring coronary artery revascularisation. A total of 30 of the 51 patients were excluded as their CTCA was a systolic scan. A total of 12 of the 51 patients were excluded because of incomplete TTE or CTCA data . The finidelines .Data were prospectively collected, analysed, and made available upon reasonable request to the corresponding author. This study complied with the principles of the Declaration of Helsinki. It was approved by the Uniting Care Health Human Research Ethics Committee (number 2019.29.307) of Brisbane, Australia. Informed consent was obtained from all patients.ED), end-systole, and diastasis (LVdias). The LA area was planimetered from the four-chamber and two-chamber views, excluding the LA appendage and pulmonary veins. LA volume was calculated using the biplane area-length method. LA volume was measured in three phases of the cardiac cycle: maximum (LAmax) at LV end-systole, diastasis (LAdias), and minimum (LAmin) at LV end-diastole. LA function parameters included (i) LA reservoir function, total emptying volume, and emptying fraction; (ii) LA conduit function, LA passive emptying volume, and emptying fraction; and (iii) LA pump function, LA active emptying volume, and emptying fraction, as previously described  or Siemens SC200 . A standard clinical imaging protocol was used for each patient. The protocol consisted of M-mode, two-dimensional, and Doppler analyses , 17. Apiescribed . Each medias/LAdias) . The iCT had a 270-ms gantry rotation time and temporal resolution of 135 ms. The collimation scan parameters were 128 mm × 0.625 mm. An intravenous injection of iodinated contrast media (Omnipaque 350) was used to opacify the coronary arteries and, subsequently, the LA and LV. The scan was acquired during a single breath hold, using the prospective electrocardiogram-gated axial step-and-shoot/sequential technique. Only patients scanned in diastasis between 75% and 81% of the R-R interval were chosen for the analysis, with the standard acquisition occurring at 78%. The LA volume was measured by excluding the LA appendage. The LV volume was measured using an automated algorithm within the cardiac software of the Philips Intellispace Portal. The diastolic function assessment, that is, the diastolic expansion index, was measured as the ratio between diastasis LV and LA volume (LV/LAdias) .t-test, χ2 test, Fisher exact test, or non-parametric Wilcoxon/Kruskal–Wallis rank-sum test was used when appropriate for comparison between Group 1 and Group 2. Pearson's correlation coefficient was used to estimate the degree of association between two quantitative variables.Continuous variables are expressed as mean ± standard deviation, and categorical variables are expressed as numbers and percentages. The two-sample p-values <0.05 were considered significant. All analyses were performed using JMP 15  and MedCalc Version 20.109 .For predefined TTE and CTCA measurements, logistic regression analysis with the DeLong method was used to assess the area under the receiver operating characteristic curve and Youden index J point with a cut-off value to differentiate patients from Groups 1 and 2. Sensitivity and specificity were calculated in a standard manner. Multivariate analysis of variance (MANOVA) was performed to determine the difference in complicated and uncomplicated subgroups of hypertension compared with the age-matched group. A multivariate correlation coefficient or likelihood ratio was used to determine the relationship between echo score and clinical parameters. For all analyses, Patient characteristics are presented in Group 1 had a higher body mass index, higher rates of hyperlipidaemia, Stage 3 chronic kidney disease, and often mild-to-moderate coronary artery plaques. Complicated hypertension with diabetes or Stage 3 chronic kidney disease was observed in 28 (29%) patients. The depression anxiety stress score  and qualp = 0.0042) with no differences in LV diameter, LVED, or LVdias. The ratios of LVED to mean wall thickness and LVED index to mean wall thickness were lower in Group 1 than in Group 2 . The LV relative wall thickness ratio was higher in Group 1 . Concentric LV remodelling was more frequent in Group 1 than in Group 2 .As shown in 2.7, and LV ejection fraction.There were no differences between the groups for the following measurements: LV mass index, LV mass/heightdias (ml) , LAdias index (ml/m2) , LAmin (ml) , and LAmin index (ml/m2) . LAmax as the absolute value or indexed (by either body surface area or height2.7) did not differ between Groups 1 and 2. The LVdias/LAdias (ml) was lower in Group 1 compared to Group 2 . Among all the studied LA function parameters, only the LA reservoir function measured by LA total emptying fraction (%) was lower in Group 1 compared to Group 2 .The analysis of the LA showed that in Group 1, the LA was bigger for the following measurements: LAp = 0.0233) and lateral wall . The mean value of the ratio of early diastolic mitral inflow to mitral annular tissue velocities (E/e’) averaged for both the septum and lateral wall was higher in Group 1 .p = 0.0009]. However, a similar percentage of patients in Groups 1 and 2 had normal or indeterminate diastolic function.dias or LAdias between the groups, whether considering the absolute value or the indexed body surface area. The ratio of LVdias/LAdias was lower in Group 1 than in Group 2 .dias/LAdias and CT LVdias/LAdias .There was a good correlation between TTE LVdias/LAdias ratio ≤1.76 had discriminatory power to differentiate patients with HHD with an area under the curve (AUC) of 0.646 (p = 0.0006). The LVdias/LAdias ratio ≤ of 1.76 had a high sensitivity of 91% but low specificity of 36%.Both TTE and CTCA parameters were analysed using receiver operating characteristics to identify patients with hypertensive heart disease (HHD), see ED index/mean wall thickness ≤57, ratio of LVdias/LAdias ≤1.62, and LA reservoir function ≤0.58 had a high discriminatory power to diagnose HHD . These four TTE-derived parameters were chosen for their overall accuracy in predicting HHD. They were grouped to obtain an overall simplified diagnostic TTE (LEDA) score. This method provided the highest discriminatory power with an AUC of 0.772 and overpowered single TTE measurements as well as the LV mass index (p = 0.0244) (p = 0.0036) and Stage 3 chronic kidney disease . A borderline but not significant relationship was observed between LEDA and obstructive sleep apnoea , as well as mild to moderate coronary artery disease . LEDA score did not exhibit a significant association with smoking history  or underlying hyperlipidaemia .Predictive modelling for TTE data includes the parameters listed in ss index . The LED 0.0244) . LEDA wa 0.0244) . FurtherThe cumulative effects of hypertension on cardiac remodelling and vascular aging are well recognised . TherefoHypertension is commonly associated with an increase in LV wall thickness, leading to LV hypertrophy. This phenomenon signifies the maladaptive response to chronic pressure overload, eventually resulting in contractile dysfunction –14, 23. dias/LAdias).In this study, we prospectively analysed changes in left heart remodelling in patients with hypertension, excluding those with underlying myocardial ischaemia or obstructive coronary disease. We used TTE-derived parameters, including LV concentricity, filling pressure, and LA function. In addition, we expanded our observations by introducing a parameter obtained from both TTE and CTCA, specifically measured during diastasis: the left heart chamber volume ratio (LVdias) and end-diastole (LAmin), but not in systole at LAmax. This pattern of LA dilatation in mid to late diastole, rather than in late systole, has been documented previously, and is associated with increasing LV filling pressure, consequent elevation in LA pressure, and, finally, augmented LA wall stress  E/e’ ratio by Doppler >8, (3) LVdias/LAdias ≤1.62, and (4) LA reservoir function ≤0.58. The concept of combining these four parameters surpassed the diagnostic utility of individual LA or LV TTE parameter, as well as the LV mass index  LVss index . Each padias/LAdias, and introducing the LEDA score, we aim to improve the diagnostic accuracy of hypertension-related cardiac changes. These findings hold promise for enhancing clinical practice and ultimately improving the long-term prognosis of patients with hypertension. More data are needed to validate the LEDA score and age-related changes. One of the potential advantages of LVdias/LAdias lies in its simplicity and ease of measurement. It is accessible through most standard TTE examinations, making it readily available in routine clinical practice. Furthermore, our study demonstrated its value when obtained through both TTE and CTCA assessments, suggesting its versatility in different imaging modalities.This study offers critical insights into the complex dynamics of left heart remodelling in hypertensive patients. By identifying novel parameters, LV