Identifying people who are at risk of being admitted to hospital  for heart failure and death, and particularly those who have not previously been hospitalised for heart failure, is a priority. We aimed to develop and externally validate a prognostic model involving contemporary deep phenotyping that can be used to generate individual risk estimates of hospitalisation for heart failure or all-cause mortality in patients with, or at risk of, heart failure, but who have not previously been hospitalised for heart failure.Between June 1, 2016, and May 31, 2018, 3019 consecutive adult patients (aged ≥16 years) undergoing cardiac magnetic resonance (CMR) at Manchester University National Health Service Foundation Trust, Manchester, UK, were prospectively recruited into a model development cohort. Candidate predictor variables were selected according to clinical practice and literature review. Cox proportional hazards modelling was used to develop a prognostic model. The final model was validated in an external cohort of 1242 consecutive adult patients undergoing CMR at the University of Pittsburgh Medical Center Cardiovascular Magnetic Resonance Center, Pittsburgh, PA, USA, between June 1, 2010, and March 25, 2016. Exclusion criteria for both cohorts included previous hospitalisation for heart failure. Our study outcome was a composite of first hospitalisation for heart failure or all-cause mortality after CMR. Model performance was evaluated in both cohorts by discrimination (Harrell's C-index) and calibration .Median follow-up durations were 1118 days (IQR 950–1324) for the development cohort and 2117 days (1685–2446) for the validation cohort. The composite outcome occurred in 225 (7·5%) of 3019 patients in the development cohort and in 219 (17·6%) of 1242 patients in the validation cohort. The final, externally validated, parsimonious, multivariable model comprised the predictors: age, diabetes, chronic obstructive pulmonary disease, N-terminal pro-B-type natriuretic peptide, and the CMR variables, global longitudinal strain, myocardial infarction, and myocardial extracellular volume. The median optimism-adjusted C-index for the externally validated model across 20 imputed model development datasets was 0·805 (95% CI 0·793–0·829) in the development cohort and 0·793 (0·766–0·820) in the external validation cohort. Model calibration was excellent across the full risk profile. A risk calculator that provides an estimated risk of hospitalisation for heart failure or all-cause mortality at 3 years after CMR for individual patients was generated.We developed and externally validated a risk prediction model that provides accurate, individualised estimates of the risk of hospitalisation for heart failure and all-cause mortality in patients with, or at risk of, heart failure, before first hospitalisation. It could be used to direct intensified therapy and closer follow-up to those at increased risk.The UK National Institute for Health Research, Guerbet Laboratories, and Roche Diagnostics International. The high prevalence, poor prognosis, and high cost of heart failure make it a global health priority.Around a third of people aged 55 years will develop heart failure.Existing heart failure prediction models have often been developed in groups of patients who are already known to be at high risk of adverse outcomes, such as patients who have already been hospitalised for heart failure, with relatively sparse, non-contemporary phenotyping, and without external validation.Evidence before this studyWe searched MEDLINE (PubMed) for studies published in English between database inception and July 5, 2021, deriving or validating multivariable risk prediction models in patients with, or at risk of, heart failure to predict adverse outcomes, including hospitalisation for heart failure and death. The search was limited to human studies. Search terms comprised: “heart failure”, “chronic heart failure”, “acute decompensated heart failure”, “heart failure with preserved ejection fraction”, “heart failure with reduced ejection fraction”, “prognostic model”, “prognostic modelling”, “prognosis”, “risk prediction”, “risk score”, “score”, “model”, “mortality”, “death”, “(re)hospitalisation”, and “(re)admission”. Heart failure is common, has a poor prognosis, and its associated health-care costs, particularly related to hospitalisation for heart failure, are high. Identifying individuals who are more likely to be hospitalised for heart failure or die before they are hospitalised is a priority. Typically, existing risk prediction models have not been subject to external validation and were developed using a high proportion of patients who have previously been hospitalised for heart failure. Such models are applicable only later in the patient pathway when patients already have a dismal prognosis, the underlying disease mechanisms might intuitively be less modifiable, and the large expenditure associated with hospitalisation for heart failure has already been incurred.Added value of this studyWe present an accurate, validated, and reliable prognostic model that provides individualised estimates of the risk of hospitalisation for heart failure and all-cause mortality in patients with, or at risk of, heart failure, before first hospitalisation. The model was derived from, and validated in, large cohorts of patients by use of contemporary, deep phenotyping. The derived and validated model showed excellent performance , and, crucially, was developed in patients before they were first hospitalised for heart failure. To our knowledge, it is the first such model.Implications of all the available evidenceThe final externally validated model is intuitive and includes key comorbidities that are in keeping with previous studies, circulating biomarkers, and measures of myocardial structure and function. We present a risk calculator to facilitate individual  risk stratification, which, when implemented, could allow the direction of intensified therapy and closer follow-up to those at increased risk, with the aim of preventing, or postponing, hospitalisation for heart failure and death, while redirecting unnecessary intervention away from those at low risk. This implementation could increase health-care efficiency, reduce unnecessary medicalisation, and facilitate research into preventive strategies.We aimed to develop and externally validate a prognostic model involving contemporary deep phenotyping with cardiovascular magnetic resonance (CMR) that can be used to generate individual risk estimates of hospitalisation for heart failure and all-cause mortality in patients with, or at risk of, heart failure, but who have not previously been hospitalised for heart failure.ClinicalTrials.gov, NCT02326324; Between June 1, 2016, and May 31, 2018, consecutive adult patients (aged ≥16 years) undergoing clinically indicated CMR at Manchester University National Health Service (NHS) Foundation Trust, Manchester, UK, were prospectively recruited into a development cohort . Measurements of ventricular mass, volumetrics, ejection fraction, and atrial area were done in accordance with recommendations from the Society for Cardiovascular Magnetic Resonance.Data were managed by use of Research Electronic Data Capture (known as REDCap).NHS Digital. Hospital Episode Statistics for Admitted Patient Care records were used to identify episodes of hospital admission and mortality status was derived from Hospital Episode Statistics-Office of National Statistics (civil registration) data. Hospital Episode Statistics data contain diagnostic coding from the International Classification of Diseases, 10th revision (ICD-10), to denote up to 20 diagnoses per episode of hospital admission or cause of death. Hospitalisation for heart failure was defined as the first hospitalisation following CMR in which heart failure (ICD-10 I50) was the primary diagnosis.Our study outcome was a composite of admission to hospital  for heart failure or all-cause mortality occurring after CMR. Time to the composite endpoint was defined as the time to the first event, with censoring at the last follow-up date if no event occurred. Outcome data were obtained from Model development is reported in accordance with Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines.We developed our model in a cohort of 3019 patients  in the validation cohort had complete data; therefore, complete cases were used for the analysis. Some candidate predictor variables were not available in the validation dataset . To account for these missing variables, a reduced version of the final model was developed in the development cohort. Specifically, we re-conducted the entire model development and internal validation processes, while excluding the predictors that were unavailable in the validation cohort. NT-pro-BNP was also not available in the validation dataset; however, BNP was available in the validation cohort, and, given that they provide similar information, BNP was substituted for NT-pro-BNP in the model.Using the pooled, optimism-adjusted calibration slope as a uniform shrinkage factor, all the predictor effects in the final developed model were penalised to account for overfitting before carrying out external validation.P=1 – S0(t)exp(prognostic index) where S0(t) is the baseline survival probability at time t  and the prognostic index is the sum of the products of the coefficients and the associated predictor.A risk calculator that provides an estimated risk of hospitalisation for heart failure or all-cause mortality at 3 years for individual patients was generated from the externally validated optimism-adjusted model. The probability of hospitalisation for heart failure or all-cause mortality was estimated by use of the following equation, derived from the Cox proportional hazards model: The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Guerbet Laboratories and Roche Diagnostics International conducted a factual accuracy check of this manuscript, but any decisions to incorporate comments were made solely at the discretion of the authors.The baseline characteristics of the development cohort (n=3019) are summarised in r=–0·77), suggesting potential collinearity .The multivariable model satisfied the proportional hazards assumption. Univariably, global longitudinal strain did show some evidence of an association with time ; however90 (0·002) all indicated excellent calibration.The median optimism-adjusted C-index for the parsimonious model across the 20 imputed datasets was 0·806 , global longitudinal strain, myocardial infarction, and myocardial extracellular volume. Optimism-adjusted model results are presented in Schöenfeld residual testing showed that the proportional hazards assumption was met, except, as before, for global longitudinal strain, which univariably showed an association with time . HoweverThe median optimism-adjusted C-index for the externally validated model across the 20 imputed model development datasets was 0·805 (95% CI 0·793–0·829) in the development cohort, and the median calibration slope, adjusted for model-fitting optimism, was 0·943 . The optRisk=1 – 0·934exp(prognostic index) whereBased on the recalibrated model, the risk of hospitalisation for heart failure or all-cause mortality at 3 years for an individual patient can be calculated from the following equation: We present an externally validated risk prediction model of hospitalisation for heart failure and all-cause mortality in patients with, or at risk of, heart failure, but who have not been previously hospitalised for heart failure. The model was derived from, and validated in, large cohorts of patients with contemporary, deep phenotyping, and provides accurate, individualised estimates of risk. To our knowledge, it is the first such model.Heart failure is common, has a poor prognosis, and its associated health-care costs, particularly related to hospitalisation for heart failure, are high. As the global population ages and factors predisposing to heart failure become more prevalent, identifying individuals with a higher likelihood of being hospitalised for heart failure or dying is, increasingly, a priority. Individual  risk stratification could allow the direction of intensified therapy and closer follow-up to those at increased risk, with the aim of preventing, or postponing, hospitalisation for heart failure and death, while redirecting unnecessary intervention away from those at low risk  and facilitating research into preventive strategies.26It is with this priority in mind that numerous heart failure prognostic models have been developed; however, few models have been validated and those that have were typically derived and validated in cohorts with a high proportion of patients who have been previously hospitalised for heart failure.Unlike many previous models,The final externally validated model is intuitive. It includes age, key comorbidities that are in keeping with previous studies ,Model performance was high; indeed, it substantially outperformed other validated heart failure prognostic models.Khan and colleaguesA limitation of this study is that all patients were undergoing CMR and so the population is potentially skewed. However, the CMR service at Manchester University NHS Foundation Trust serves several district hospitals across the northwest of England, in addition to Manchester University NHS Foundation Trust (the tertiary cardiac centre); indeed, 57·1% of patients in the development cohort were from district hospitals. Thus, our study population is more representative than those of many studies that have derived heart failure prognostic models, which have often been restricted to specialist centres, have used randomised controlled trial populations, or have recruited specific heart failure subgroups.The recruitment period for the validation cohort preceded that for the development cohort. However, recruitment criteria were identical and image acquisition and analysis adhered to recommendations from the Society for Cardiovascular Magnetic Resonance. Cohorts with the required level of contemporary deep phenotyping to enable validation of the derived model are rare; indeed, as far as we are aware, the validation cohort is the only such cohort. External validation is a strength of our study, representing rigorous use of the available data. The high performance of our model in the external validation cohort, despite some differences in cohort characteristics compared with the development cohort, shows the robustness of the model.Defining hospitalisation for heart failure as the first hospitalisation following CMR in which heart failure was the primary diagnosis is specific and in keeping with other studies,Another potential limitation of our model is its applicability, given that many patients do not have access to CMR. However, given that stratified and precision medicine are the focus of much of medical science, it is hoped that showing the unique prognostic value of CMR measurements of cardiac structure and function will catalyse clinical implementation.In conclusion, we developed and externally validated a risk prediction model that utilises contemporary deep phenotyping to provide accurate, individualised estimates of risk for hospitalisation for heart failure and all-cause mortality in patients with, or at risk of, heart failure, but who have not previously been hospitalised for heart failure.christopher.miller@manchester.ac.uk. Requesters will be required to sign a data access agreement.Deidentified participant data will be made available to requesters 1 year after the date of publication, with no end date to availability. Data will be shared after an appropriate proposal is submitted and can be used for any purpose. Proposals should be directed to EBS serves as an adviser for HAYA Therapeutics and consults for PureTech Health. PFB was in receipt of a Joint Alliance Medical and University Hospital of South Manchester Fellowship Salary Support Grant. JHN has a part-time appointment at Bioxydyn. TM serves as the clinical lead for the National Heart Failure Audit and has received speaker fees from Novartis, AstraZeneca, and Vifor. CAM has served on advisory boards for Novartis, Boehringer Ingelheim and Lilly Alliance, and AstraZeneca; serves as an adviser for HAYA Therapeutics and PureTech Health; and has received research support from Amicus Therapeutics, Guerbet Laboratories, Roche, and Univar Solutions . All other authors declare no competing interests.


To investigate the application effect of 24 h dynamic electrocardiogram in the diagnosis of asymptomatic myocardial ischemia with arrhythmia in elderly patients with coronary heart disease.  A total of 206 elderly patients suspected of coronary heart disease (CHD) with asymptomatic myocardial ischemia and arrhythmia were selected as the research subjects. 24 h dynamic electrocardiogram and conventional electrocardiogram examinations were conducted. Coronary angiography was used as the gold standard to observe the performance of the two examination methods in the diagnosis of asymptomatic myocardial ischemia with arrhythmia in elderly patients with CHD. P < 0.05). The detection rate of arrhythmia types by 24-hour dynamic electrocardiogram was significantly higher than that of conventional electrocardiogram (P < 0.05).  Coronary angiography showed 174 positive cases and 32 negative cases among the 206 patients. The diagnostic results of a conventional electrocardiogram showed 150 positive cases and 20 negative cases. Its sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 86.21%, 62.50%, 82.52%, 92.59%, and 45.45%, respectively. The diagnostic results of 24 h dynamic electrocardiograms showed 168 positive cases and 29 negative cases. Its sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 96.55%, 96.63%, 95.63%, 98.25%, and 82.86%, respectively. The above results indicated that 24 h dynamic electrocardiogram was significantly better ( 24 h dynamic electrocardiogram is helpful for the diagnosis of asymptomatic myocardial ischemia with arrhythmia in elderly patients with CHD and can improve the detection rate, thereby providing a basis for clinical diagnosis and treatment. Q waves and ST-segment elevation in time, with occasional irregular fluctuations. Therefore, it is also of great significance for clinical guidance of treatment and prognosis evaluation [Coronary heart disease (CHD) is a clinical coronary atherosclerotic heart disease. In general, the main pathogenesis of CHD is vascular stenosis or obstruction caused by atherosclerosis in patients, resulting in myocardial hypoxia and ischemia, so myocardial ischemia is one of the main symptoms of CHD . With thaluation . HoweverA total of 206 elderly patients suspected of having CHD with asymptomatic myocardial ischemia and arrhythmia were selected as the research subjects. Inclusion criteria were as follows: ① Examined by the electrocardiogram stress test, myocardial imaging, coronary angiography, and other examinations, patients met the indications of asymptomatic myocardial ischemia with arrhythmia in CHD ; ② patieT wave in the same lead is smaller than the R wave [Conventional electrocardiogram: After admission, we performed an electrocardiogram examination, took the supine position, cleaned the electrode placement site and applied the special conductive paste to reduce skin resistance, connected the electrocardiogram machine to the power supply and ground wire, and the voltage was set to to 10 mm/mV, input impedance ≥100 KΩ, frequency response 100 Hz, paper feeding speed 25 mm/s, etc., adjusted the sensitivity controller, traced the conventional 12 leads, in turn, gave a clear indication of the patient's name, department, date, time, and other information. The positive diagnostic criteria of a conventional electrocardiogram are ST segment level drops in the range of 0.05∼0.2 mV, the ST segment is abnormally elevated, and the e R wave .J point), the distance reaches 0.1 mV, the continuous abnormal fluctuation time is about 1 min, and the interval between two seizures is longer than 1 min [24 h dynamic electrocardiogram: took the same supine position, the patch area should be kept clean, after connecting to the power supply and connecting the electrodes, the ST-T segment changes, duration, heart rate variability, etc. were recorded by using a BS6930 Holter electrocardiograph . During the examination, cotton loose clothing should be selected as much as possible to reduce electrostatic interference; the dynamic changes of 12 leads should be traced in turn, and the patient information should be noted in detail. The positive diagnostic criteria of 24 h dynamic electrocardiogram: the ST segment is in a downward state  ∗ 100%; accuracy = (true positive number + true negative number)/total number ∗ 100%; positive predictive value = true positive number/ ∗ 100%; negative predictive value = true negative number/ ∗ 100%.We took coronary angiography as the gold standard to observe the diagnostic performance of two inspection methods, including sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. Sensitivity = true positive number/ According to the electrocardiogram start and end characteristics, heart rate, rhythm, and fluctuations recorded the detection rate of arrhythmia types in the two groups, including ventricular tachycardia, ventricular arrhythmia, atrial arrhythmia, and supraventricular tachycardia.t and X2 tests were performed respectively. P value < 0.05 shows that there is a significant difference between the groups.EXCEL spreadsheet was used for statistical analysis of experimental data, and SPSS 22.0 statistical tools were used for analysis and processing, with , as shown in Comparing the diagnostic performance of the two groups, the diagnostic performance of 24 h dynamic electrocardiogram was significantly better than that of a conventional electrocardiogram , as shown In the 24-hour dynamic electrocardiogram test of all patients, there are four arrhythmia types including ventricular tachycardia, ventricular arrhythmia, atrial arrhythmia, and supraventricular tachycardia. The detection rate of arrhythmia types in the 24 h dynamic electrocardiogram group was 80.58% (166/206), which was significantly higher than that in the conventional electrocardiography group, which was 70.39% (145/206) (CHD is also known as ischemic heart disease. When the continuous release of cytokines makes fibrous adipose tissue lesions and in the blood pressure, vascular branch formation and platelet aggregation, and other abnormal hemodynamic conditions, led to arterial intima, function damage, and atherosclerosis. Atherosclerosis is one of the main pathological mechanisms of CHD. Atherosclerosis and CHD are common diseases that lead to organ diseases, myocardial ischemia, and hypoxia. Relevant studies  have conCoronary angiography, as the gold standard for diagnosing CHD, can quantitatively measure coronary lesions by puncturing the artery with a custom-made catheter and visualize it with a contrast agent and observe the arterial blood flow and myocardial perfusion to select an appropriate treatment method. However, coronary angiography is expensive and requires certain medical equipment and technology, so it cannot be widely used in some grass-roots hospitals and township hospitals . TherefoT wave, and heart rate in detail in patients, providing important reference information for clinical diagnosis and treatment. In addition, patients can wear it tightly, which can reduce restrictions on their activities and is more acceptable to patients [As one of the inspection methods to reflect the bioelectric changes of human myocardial cells, electrocardiography can observe whether there is myocardial ischemia and the existence of ischemic blood vessels to diagnose the disease. However, routine electrocardiography detects the resting state of the patient, which may lead to misdiagnosis or missed diagnosis of the patient, thus affecting the follow-up treatment . The emepatients .To sum up, 24 h dynamic electrocardiography can play a great advantage in detecting electrocardiography signals in asymptomatic myocardial ischemia with arrhythmia in elderly patients with CHD, and its diagnostic efficiency and arrhythmia detection rate is significantly higher than those of conventional electrocardiography. In addition, compared with arteriography, its detection cost and equipment requirements are relatively low and simple, and there is little difference from conventional electrocardiography. Therefore, 24-hour dynamic electrocardiography is of great significance in the early diagnosis, treatment, and prevention of patients with CHD and arrhythmia, which is worth popularizing.


Inflammatory cardiomyopathy (IC) is a syndrome with chronic myocarditis and cardiac remodeling. This study aimed to explore predicting factors of adverse outcomes in patients with IC secondary to idiopathic inflammatory myopathy (IIM‐IC).By means of a single‐center retrospective study, 52 patients with IIM‐IC at Peking Union Medical College Hospital were identified from January 1999 to June 2019. Electrocardiogram and echocardiography data were analyzed for the primary outcome  and secondary outcomes , using regression and survival analysis.HR = 12.315) and LVEF ≤40% (HR = 5.616) were independent risk factors for all‐cause death.The prevalence of atrial fibrillation, ventricular tachycardia, Q‐wave abnormality, left ventricular conduction abnormalities, and reduced left ventricular ejection fraction (LVEF) (≤40%) were 65.4%, 67.3%, 67.3%, 61.6%, and 50.5%. After a median follow‐up of 2 years (IQR 0.8–3.0), 26 cases were readmitted due to heart failure. Twenty‐two deaths were recorded, including 20 cardiogenic deaths. Among the patients with adverse events, the incidence of poor R‐wave progression, low‐voltage of the limb leads, Q‐wave abnormality, QRS duration >130 ms, left ventricular enlargement, and impaired systolic function were higher. Kaplan–Meier analysis showed that Q‐wave abnormality, limb leads low‐voltage, LVEF ≤40%, and left ventricular end‐diastolic dimension >60 mm were correlated with shorter survival. However, multivariate Cox regression analysis revealed that only Q‐wave abnormality (Q‐wave abnormality and reduced LVEF are predictive of poor prognosis in patients with IIM‐IC. Systemic evaluation of IC in patients with IIM. Initial electrocardiographic images and echocardiographic reports during their first hospitalization were analyzed by 2 cardiologists who were blinded of the patient’s illness.2.3The baseline electrocardiographic variables were analyzed: resting heart rate, electronic axis and voltage, QRS duration , corrected QT duration , and presence and distribution of Q‐wave abnormality. Other arrhythmias such as conduction disturbance, atrial fibrillation (AF), and ventricular tachycardia were also recorded. According to echocardiography , left ventricular end‐diastolic dimension (LVEDD), left ventricular fractional shortening, and left ventricular ejection fraction , tricuspid regurgitation peak velocity (TRV), ventricular wall motions, and presence or absence of pericardial effusion were recorded. Reduced LVEF was defined as LVEF less or equal to 40%  was considered statistically significant.Data were analyzed using the SPSS version 19.0 software . All data were expressed as mean ± standard deviation (SD) and median  for normally and non‐normally distributed data, respectively, and as a percentage when appropriate. To compare difference between groups, independent samples T‐tests and Mann–Whitney tests were used for continuous variables that were normal and not normally distributed, respectively. The chi‐squared or Fisher’s exact tests were used for categorical data as appropriate. Univariate and multivariate binary logistic regression model was used to identify factors associated with adverse events. The possible risk factors were evaluated by Kaplan–Meier survival analysis along with log‐rank tests. 33.1The clinical characteristics and treatment strategies of the study patients are shown in Table All the involved patients were followed for a median of 2 years (IQR 0.8–3.0 years) and 22 deaths were recorded. Cardiogenic death was noticed in 20 cases; the other two cases of deaths were caused by infective complication and progressive respiratory failure, respectively. Twenty‐six cases were readmitted due to HF and five cases were implanted with implanted cardiac device, including 3 of implantable cardioverter defibrillator. IIM‐IC patients that required rehospitalization for HF or suffered from all‐cause death had worse baseline functional status (greater percentage NYHA Class III‐IV) and higher levels of NT‐proBNP compared to IIM‐IC patients who did not have adverse events Table .3.23.2.1The average heart rate recorded by the electrocardiogram was 82 ± 19 beats per minute. Pause greater than 2 seconds in sinus rhythm or greater than 3 seconds in AF and advanced atrioventricular block were noticed in 11 and 2 patients, respectively. Premature ventricular contraction was present in 90.4% of involved patients, while ventricular tachycardia could be seen in more than two thirds of our cases (67.3%) Figure . Most of3.2.2p = 0.038)     at baseline Figure , the pre) Figure , low‐vol) Figure , Q‐wave ) Figure  and QRS ) Figure  at basel% at base3.2.3The echocardiographic reports of all patients were consistent with the morphological feature of DCM and were mainly manifested as mildly dilated left ventricle (LVEDD: 53.7 mm ± 7.9 mm) and impaired left ventricular systolic function (LVEF: 37.8% ± 11.5%). Twenty‐six patients (50.5%) met the definition of reduced LVEF. Left ventricular diastolic dysfunction was common 29/52). There were 30 patients with left ventricular enlargement, with a LVEDD of 53.7 ± 7.9 mm , low voltage of the limb leads , LVEDD >60 mm , and reduced LVEF  were significantly associated with adverse events . However, after adjusted for baseline NYHA cardiac function and serum levels of NT‐proBNP in multivariate Cox regression model, only Q‐wave abnormality  and reduced LVEF  were the independent predictors for adverse events  were independent predictors for adverse events and shorter survivals.The electrocardiogram is an initial, sensitive, and noninvasive examination to identify myocardial involvement in patients with IIM. Electrocardiographic alterations were reported in 30%–80% of cases of IIM  matching with the general population (N = 7923), discovering an increased risk of myocardial infarction in patients with IIM (adjusted HR = 3.89) after a follow‐up of 15 years  myocardial inflammation leading to myocyte degeneration and interstitial fibrosis  was the independent risk factors of mortality , Dr Yingxian Liu has grant support from the National Natural Science Foundation of China (82000470), and the other authors report no conflicts.Not applicable.Ligang Fang and Wei Chen performed conception and design; Ligang Fang and Yingxian Liu involved in administrative support; Xue Lin, Yanlin Zhu, and Wei Wu involved in provision of study materials or patients; Xiaohang Liu and Fuwei Jia performed collection and assembly of data; Yingxian Liu and Wei Wu performed data analysis and interpretation; Yingxian Liu drafted the manuscript; Ligang Fang, Jeffrey Hsu, and Wei Chen revised the manuscript. All authors approved the final version of manuscript.This study is approved by the Ethics Committee of the Peking Union Medical College Hospital and has been registered in Clinical trials (NCT 03885375).Fig S1Click here for additional data file.Supplementary MaterialClick here for additional data file.


Using a multiple logistic regression model with predictors such as right ventricular longitudinal strain (RVGLS), LV ejection fraction (LV EF), and hemoglobin, abnormal myocardial iron overload can be predicted. This model demonstrates an AUC of 78.3%, a sensitivity of 72%, and a specificity of 76%. In the group with preserved RVEF > 53%, the left ventricular radial strain (LVGRS) (p = 0.001), right ventricular radial strain (RVGRS) (p = 0.000), and right ventricular basal circumferential strain  (p = 0.000) CMR-FT strain values are significantly lower than those of the control group (p > 0.05). There was no significant correlation between the LVGLS and T2*. RVGLS was ranked among the most accurate predictors of abnormal myocardial iron overload. The LVGRS, RVGRS, and RVGCS-basal CMR-FT strain values were the best predictors of subclinical RV dysfunction in the group with preserved RVEF. The most accurate way to diagnose MIO is still T2*, but FT-strain can help us figure out how MIO affects the myocardium from a pathophysiological point of view.In patients with thalassemia major (TM), cardiac magnetic resonance feature-tracking (CMR-FT) has been shown to be an effective method for diagnosing subclinical left ventricular (LV) dysfunction. This study aimed to determine whether CMR-FT could detect abnormal RV dysfunction in patients with a normal right ventricular ejection fraction (RVEF). We performed a retrospective analysis of TM patients admitted to Dubai’s Rashid Hospital between July 2019 and March 2021. The inclusion criteria were TM patients with SSFP cine with T2* (T2*-weighted imaging), while exclusion criteria included any other cardiovascular disease. When there was no myocardial iron overload (MIO) (T2* ≥ 20 ms) and when there was significant MIO (T2* < 20 ms), the CMR-FT was used to correlate with EF. Among the 89 participants, there were 46 men (51.7%) and 43 women (48.3%), with a mean age of 26.14 ± 7.4 years (range from 10 to 48 years). Forty-six patients (51.69%) did not have MIO, while 43 individuals did (48.31%). Thirty-nine patients (32.6%) were diagnosed with severe MIO, while seventeen (19.1%) were diagnosed with mild to moderate MIO. A significant correlation existed between RVEF and T2* values (r = 0.274,  Thalassemia results in chronic hemolytic anemia, the most prevalent monogenetic disease in the world, and affected patients frequently need blood transfusions . MIO is Due to repeated blood transfusions, myocardial deformations change, resulting in variations in strain values. FT-CMR is a highly accurate method for detecting myocardial dysfunction and myocardial fiber deformation, especially in the earliest stages of cardiac disease ,9. By evRecent research indicates that myocardial iron deposition is significantly linked to RV dysfunction, corroborating the decline in LV function associated with increased cardiac iron overload ,14. A prBetween July 2019 and March 2021, we conducted a retrospective analysis of TM patients referred by the Thalassemia clinic for cardiac MR examination to the Rashid Hospital in Dubai. The inclusion criteria included a confirmed diagnosis of TM based on previous measurements . ExcludeIn an anemia-induced high-output state, the ejection fraction of patients with hemoglobinopathies and other hematologic disorders is typically normal or elevated. Consequently, a typical LVEF and RVEF range was determined by averaging the values obtained from our TM cohort in the absence of evidence of myocardial iron overload. The 95% Confidence Interval for the mean LV EF was , and the 95% Confidence Interval for the mean RV EF was . Based on these upper limits of the means of LVEF and RVEF, as it says in the manuscript, we put the patients into two groups: normal and abnormal.We conducted a retrospective screening of 24 individuals who had previously been evaluated prospectively at the same facility and were found to be in excellent health. Exclusion criteria included known cardiovascular risk factors, any pre-existing diseases or medications, an impaired left ventricular ejection fraction (LVEF) of less than 55%, or abnormal findings on a 12-lead electrocardiogram or magnetic resonance imaging scan (MRI). Insufficient CMR data for feature tracking analysis led to the exclusion. An ethics committee authorized all of the studies.Magnetom Aera was utilized to conduct a standard cardiac MRI . Short-axis, horizontal long-axis, three-chamber view, and vertical long-axis cine series were acquired using a steady-state free precession sequence with typical TR/TE values of 2.2/1.1 ms at 1.5 T . The short-axis cine images consisted of 10–12 sections, each 8 mm thick and separated by a 2 mm gap, spanning from 1 cm above the mitral valve plane to the apex. T2* was measured using a single breath-hold multi-echo gradient-echo sequence. As previously described, the scanning for myocardial T2* measurement was synchronized to the cardiac cycle using standard ECG gating . A 10 mmAll CMR data were retrieved and analyzed on a computer . This method is based on an incompressible volume-based method that has been previously validated for accurate biventricular anatomical monitoring. This method is used for biventricular anatomical monitoring . An expet-test for normally distributed data and the Mann–Whitney U test for non-normally distributed data were used to compare the groups. The correlation between two standard variables was evaluated using Pearson’s correlation coefficient and Spearman’s rank correlation coefficient. The Chi-square test, or Fisher’s exact test, was used to compare categorical variables represented as counts and percentages. Receiver operating characteristics (ROC) analysis and pairwise comparisons of areas under the curves were used to determine the accuracy of patients with MIO classification. The DeLong method compares the regions beneath the curves (AUC). Youden’s test was used to determine the cut-off value. A one-sample t-test was used for normal variables, whereas for non-normal variables, a Wilcoxon signed-rank test was used.SPSS version 20.0 , a statistical program for the social sciences, was used to summarize and analyze the data. Depending on the normality of the data, continuous variables were expressed as the mean standard deviation or medians with interquartile ranges. The Shapiro–Wilk test was used to determine whether the data were normally distributed. The Student’s The retrospective study included 89 individuals with thalassemia major. There were 46 men (51.7%) and 43 women (48.3%), with a mean age of 26.14 ± 7.4 years (range from 10 to 48 years). There were 46 patients without MIO (51.69%) and 43 patients with MIO (48.31%). Thirty-nine patients (32.6%) had severe MIO , while eighteen patients (19.1%) had mild to moderate MIO  . In totap = 0.014) and LVEF and T2* values . LVESV/BSA and LVM were significantly greater in the MIO group compared to the control group (p = 0.02). There was no discernible variation in the volumes of the right ventricle  . Signifientricle .p = 0.015), Hb , and RVGLS . The correlations were significant despite being weak. In addition, there is no correlation between age and T2* values . The scatter plots depict the relationship between septal T2* values and RVGLS, LVEF, and RVEF values , Hb (AUC = 0.68), and RVGLS (AUC = 0.62) are not statistically significant for identifying MIO. In conjunction with the predictors LVEF, Hb, and RVGLS, a multiple logistic regression model was employed to improve the prediction of abnormal myocardial iron overload. The AUC was 0.783, with a sensitivity of 72% and a specificity of 76% (With an area under the ROC curve (AUC) of 0.62, an RVGLS with a cut-off value of −20.68% could predict pathological myocardial iron overload (sensitivity = 67.45% and specificity = 58%). Moreover, our findings indicate that an LV EF cut-off value of 56.26% (sensitivity of 79% and specificity of 47.8%) and a Hb cut-off value of 9.35 (sensitivity of 56.5% and specificity of 79%) could predict myocardial iron overload. The y of 76% . p = 0.674) of patients with normal RVEF and 32.6%  of patients with normal LVEF have abnormal MIO , RVGRS (p = 0.000), RVGCS (p = 0.007), and RVGCS-basal (p = 0.000) in the category with LVEF > 60% are significantly lower than in the control group, as shown in p = 0.761), all strain values in the category LVEF ≤ 60% are significantly lower than those of the control group with a p-value of 0.05. In terms of RVGLS values, there is no statistically significant difference between the control group and the abnormal LVEF group.The levels of right ventricular and left ventricular strain in the normal MIO and abnormal MIO groups are compared to those of the control group in p = 0.935) and RVGCS-apex (p = 0.076). Additionally, the strain values of LVGRS, RVGRS, and RVGCS-basal are considerably lower than those of the control group (p < 0.05) in the category of RVEF > 53% . These abnormal strain parameters suggest that, in patients with preserved RVEF (>53%), strain imaging can more accurately predict the malfunctioning of the RV. The second observer repeated measurements on ten patients selected at random to assess their repeatability. CMR-FT was utilized in this study to investigate the association between MIO and biventricular function. Our results reveal a substantial relationship between RVEF and T2* levels, as well as between LVEF and T2* values . PatientRezaeian et al. found a statistically significant correlation between LVGLS and LVGCS, but not between LVGRS and T2* . One posThe literature regarding the significance of right ventricular involvement in TM remains scant. Due to the right ventricle’s complicated anatomy and muscle patterns, cardiovascular magnetic resonance (CMR) has been regarded as the gold standard for evaluating the right ventricle’s dependable function and chamber size ,15,16,17As shown by necropsy ,27, the Myocardial iron deposition is also strongly correlated with right ventricular dysfunction, which reflects the decrease in LV function associated with increased myocardial iron loading and lower T2* . The subOur study has a number of limitations. The method was executed in a single-center arrangement with a single-vendor application. The absence of well-established T2* sequences and the inability to consistently analyze them continue to restrict the availability of software to calculate CMR-derived strain parameters. In a preliminary investigation, we were able to demonstrate that RVGLS may have predictive utility. However, this early experiment was conducted on a modest scale, with only 89 participants. Our study is limited by the small sample size of patients with MIO; hence, additional prospective studies with larger study populations are required. A follow-up study is necessary to determine how these individuals’ symptoms progressed from asymptomatic to clinical HF/LV failure. Additionally, biochemical markers such as B-type natriuretic peptides, which are thought to be the best way to find subclinical cardiac dysfunction, were not looked into.RVGLS was the most accurate predictor of myocardial iron overload. CMR-FT was able to detect significant decreases in RVGLS, RVGRS, and RVGCS-basal strains in TM patients with preserved RVEF, allowing us to characterize these patients as having right ventricular dysfunction despite their preserved ejection fraction. In the majority of TM patients, a decreased RVEF was associated with MIO. FT-strain will contribute to our pathophysiology understanding of how MIO affects the myocardium, although T2* will remain the diagnostic gold standard. In addition, serial strain analysis can assist in finding therapeutic strategies to increase the time between the onset of subclinical strain change in the right or left ventricle and the onset of symptomatic heart failure in asymptomatic individuals.


In this paper, we highlight the current knowledge on the SOCE contribution to the LV and RV dysfunctions, as SOCE molecules are present in both compartments. he relative lack of studies on RV dysfunction indicates the necessity of further investigations, a significant challenge over the coming years.Right ventricular failure (RVF) is the most important prognostic factor for morbidity and mortality in pulmonary arterial hypertension (PAH) or pulmonary hypertension (PH) caused by left heart diseases. However, right ventricle (RV) remodeling is understudied and not targeted by specific therapies. This can be partly explained by the lack of basic knowledge of RV remodeling. Since the physiology and hemodynamic function of the RV differ from those of the left ventricle (LV), the mechanisms of LV dysfunction cannot be generalized to that of the RV, albeit a knowledge of these being helpful to understanding RV remodeling and dysfunction. Store-operated Ca In pulmonary arterial hypertension (PAH), the elevated pulmonary vascular resistance due to distal pulmonary artery obstruction ultimately induces right ventricular failure (RVF) . Heart fExcessive RV dilatation triggers a tricuspid regurgitation favoring venous congestion, quickly assessed by clinical signs , biochemical markers (elevated NT-proBNP or BNP), and ultrasonography. It also eventually leads to the protrusion of the interventricular septa toward the LV, impairing its filling and contractility. These signs of RV dysfunction are critical predictors of poor prognosis, suggesting an impending HF and a high risk of death by cardiogenic shock . BecauseCurrently, treatment of RV dysfunction is based on blood volume management, using mainly diuretics to reduce RV overload while carefully avoiding systemic hypotension. In the most severe cases, inotropes and vasopressors may be needed to maintain a sustainable cardiac output . None ofThe RV is a crescent-shaped structure linked to the venous system from one side and the pulmonary circulation from the other, through the tricuspid and the pulmonary valves, respectively. Its free wall is thinner than the LV myocardium (3–5 mm versus around 1 cm) for a volume that is 10–15% greater and a mass one-third to one-sixth smaller ,9. ThreeThese anatomical features give the RV greater compliance, allowing the venous return variations to absorb and provide a stable stroke volume toward the low-impedance pulmonary circulation while using only one-fourth of the LV stroke work. Subsequently, the RV is more vulnerable to significant increments in pulmonary arterial pressure.The anatomical differences between the RV and LV are the result of a different embryological origin, developed during the cardiac morphogenesis from the third to the eighth week of gestation. The LV arises from the primitive heart tube, also named the first cardiac field. In contrast, the RV is formed from the anterior part of the “second heart field”, cardiac precursor cells migrating towards the extremities of the primitive heart tube . In the The nourishing coronary blood flow, supplied by the right coronary artery in 80% of the population, occurs in both diastole and systole (mainly during diastole in the LV) but is more vulnerable to systemic hypotension and intracardiac pressure increase. Nevertheless, the RV’s relative resistance to ischemia is partially explained by lower oxygen consumption and higher oxygen extraction reserve at rest. Moreover, the expression of the anaerobic glycolytic enzyme is higher in RV than in LV cardiomyocytes . PotentiThe RV structure and function assessment are also more challenging than the LV. Its retrosternal position and complex geometry complicate echocardiography evaluation. Metabolic imaging is not yet feasible, as the free wall is too thin. Right-heart catheterization is the most accurate tool to measure hemodynamic features, especially to calculate pulmonary vascular resistance, but it is not a routine test. Compared to the LV, RV conductance studies are technically more challenging, partly because of the difficulty of obtaining reliable ventricular volumes without magnetic resistance imaging .2+ concentration ([Ca2+]i). Ca2+ mishandling is a hallmark of left and right HF i is fundamental for almost all cellular processes. In the cardiac compartment, the contraction of cardiomyocytes is mainly controlled by the ECC. The depolarization during action potential (AP) activated the L-type Ca2+ channels (LTCC). The resulting small Ca2+ influx activates massive Ca2+ release from the sarcoplasmic reticulum (SR) through the type 2 ryanodine receptor (RyR2): a Ca2+-induced Ca2+ release (CICR) process that controls contractile myofilaments. Other processes could also participate in cardiomyocyte Ca2+ homeostasis, notably the store-operated Ca2+ entry (SOCE) as described herein.The common pathophysiology of LVF and RVF is cellular remodeling, which is regulated and coincides with the remodeling of the intracellular Caright HF ,15 and i2+ depletion, an important process in modulating [Ca2+]i in most cell types, first described by Putney in 1989 i transients amplitude, SR Ca2+ load, cardiomyocyte contractility, and sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) expression, in which the protein tyrosine kinase (Pyk2)/mitogen-activated protein kinase (MEK)/ERK cascade is, in part, involved phenyl}-4-methyl-1,2,3-thiadiazole-5-carboxamide or YM-58483) ,124,125 2+ handling by preventing the Ca2+ cycling mishandling, SERCA2a downregulation and fibrosis, without causing adverse effect. Our findings suggest that Orai1 inhibition has a potential favorable hemodynamic value to protect the heart from maladaptive hypertrophy and might represent a new inotropic support to help to relieve systolic dysfunction [We have demonstrated that Orai1 function contributes to human pulmonary arterial hypertension (PAH) and to several preclinical models of pulmonary hypertension (PH). We have showed that Orai1 inhibition, by BTP2, 5J4, or JPIII, corrects in vitro the aberrant phenotypes of human pulmonary artery smooth muscles cells and attenuates in vivo PH in rat models, suggesting that Orai1 inhibition should be considered a relevant therapy in PAH . We havefunction . Taken tContrary to Orai1 blockers, existing TRPC channel inhibitors are not selective of all TRPC channel isoforms. For example, the xanthine-based inhibitors inhibit TRPC1, TRPC5, and TRPC6 at nanomolar concentrations ,138. TheSome of them can discriminate each TRPC isoform in vitro by using specific concentrations, but their use in vivo is challenging, due to their lack of selectivity at higher concentrations. Moreover, some compounds are not stable in vivo, which prevents their use in preclinical or clinical research. The development of selective TRPC channel inhibitors is needed and should be accelerated by recent cryo-EM structure discovery ,149. Dev2+ mishandling in LV dysfunction and could also be involved in RV dysfunction. Nevertheless, few studies have investigated the role of SOCs in the development of RV dysfunction. Additionally, the existing studies were performed in small animal models of RV dysfunction caused by pulmonary vessel remodeling. Further basic research studies are needed to decrypt the contribution of SOCE in RV remodeling in a large animal model or pulmonary arterial banding animals, and to investigate SOCs as novel potential therapeutic options during RV dysfunction.RVF is the most common cause of death in patients with PH, as the RV rapidly switches from adaptive to maladaptive hypertrophy in contrast to the LV. Although stopping or slowing down the progression of the RV disease appears necessary to avoid double transplantation, no treatment explicitly addresses RV dysfunction. As summarized in this review, SOCs are crucial for Ca


Poor outcome left heart defects had higher N-terminal precursor of B-type natriuretic peptide  vs. favorable outcome 617.0 pg/mL (389.8–1087.8) vs. poor outcome 1450.0 pg/mL (919.0–1645.0), p = 0.001) and drastically reduced soluble fms-like tyrosine kinase-1 concentrations  vs. favorable outcome (1848.3 pg/mL (646.9–2313.6) vs. poor outcome 259.0 pg/mL (182.0–606.0), p < 0.001). Results showed that fetuses with left heart defects present a distinct cord blood biomarker profile according to their outcome. Fetal echocardiography has limited prognostic ability in the evaluation of left-sided congenital heart defects (left heart defects). Cord blood cardiovascular biomarkers could improve the prognostic evaluation of left heart defects. A multicenter prospective cohort (2013–2019) including fetuses with left heart defects  subdivided according to their outcome (favorable vs. poor), and control fetuses were evaluated in the third trimester of pregnancy at three referral centers in Spain. Poor outcome was defined as univentricular palliation, heart transplant, or death. Cord blood concentrations of N-terminal precursor of B-type natriuretic peptide, Troponin I, transforming growth factor β, placental growth factor, and soluble fms-like tyrosine kinase-1 were determined. A total of 45 fetuses with left heart defects (29 favorable and 16 poor outcomes) and 35 normal fetuses were included, with a median follow-up of 3.1 years (interquartile range 1.4–3.9). Left heart defects with favorable outcome showed markedly increased cord blood transforming growth factor β  vs. favorable outcome 51.7 ng/mL (13.8–73.9) vs. poor outcome 25.1 ng/mL (6.9–39.0),  Left-sided congenital heart defects (left-CHD) are the most common group of severe congenital heart defects and a major contributor to neonatal morbi-mortality . In specSeveral existing biomarkers are promising candidates. B-type natriuretic peptide (BNP) and its N-terminal precursor (NT-proBNP) have demonstrated utility in screening for CHD in newborns  and in pAdditional biomarkers with a possible role in CHD are placental growth factor (PlGF) and its soluble receptor soluble fms-like tyrosine kinase-1 (sFlt1). PlGF regulates trophoblastic endothelial growth and is expressed by cardiomyocytes affecting ventricular remodeling in response to stress ,13,14. sThus, a differential expression profile of BNP, TGFβ, Troponin I, PIGF, and sFlt1 in cord blood could improve our understanding of cardiac remodeling in CDH and eventually help to identify those cases with poorer prognosis. We designed a prospective, multicenter study to measure cord blood biomarkers in fetuses with left-CHD and evaluate its association with disease severity.A prospective multicenter cohort study was conducted between 2013 and November 2019, including fetuses prenatally diagnosed with left-CHD. The cardiac outcome of these fetuses was regularly evaluated, and analysis was performed in terms of cardiac outcome. Fetuses with structurally normal hearts were also included as a non-exposed cohort. Pregnancies of women older than 18 years with accurate gestational age calculated by first-trimester crown–rump length  were conFetuses with left-CHD were recruited at the Fetal Cardiology Units from three tertiary Spanish referral centers: BCNatal  and Hospital Vall d’Hebrón in Barcelona, and Hospital La Paz in Madrid. The group of left-CHD included aortic coarctation (CoA), aortic stenosis (AoS), hypoplastic left heart syndrome (HLHS), and complex left-CHD with multilevel left ventricular (LV) tract obstruction, including complete or incomplete Shone syndrome. Fetuses with CoA were included based on high prenatal echocardiographic suspicion (significant right dominance and aortic isthmus diameter < −2 z-score)  with posControl fetuses with structurally normal hearts were recruited from singleton uncomplicated and spontaneously conceived pregnancies attended at the Maternal-Fetal Medicine Department at BCNatal in Barcelona. They were matched for gestational age (±2 weeks) at scan with left-CHD fetuses. Exclusion criteria in this group included pre or postnatal diagnosis of CHD, extracardiac malformations, genetic anomalies or conditions potentially affecting fetal cardiac function, or cord biomarkers such as intrauterine growth restriction ,22,23,24Standard obstetric ultrasound and fetal echocardiography were performed using a Siemens Sonoline Antares  or Voluson E8  using a curved-array 2–6 MHz transducer. Fetal ultrasound was performed according to recommended guidelines and included calculation of estimated fetal weight  and centThe fetal cardiac morphometric assessment included cardiothoracic ratio ,35, cardCardiac function evaluation included heart rate, right ventricular fractional area change , LV shorg for 10 min at 4 °C. Serum was separated using centrifugation at 2000× g for 10 min at room temperature. Sample aliquots were immediately stored at −80 °C until assayed.Cord blood samples were obtained from the umbilical vein after cord clamping at birth. Plasma was separated from ethylenediaminetetraacetic acid-treated blood using centrifugation at 1400× N-terminal precursor of B-type natriuretic peptide (NT-proBNP) and Troponin I concentrations was measured in plasma by electrochemiluminescence immunoassay using Siemens Atellica IM NT-proBNP and High Sensitivity Troponin I, respectively . Transforming growth factor β1 (TGFβ) was measured in serum by conventional ELISA assay Quantikine Human TGF-beta1 . Concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt1) were determined in serum by the fully automated Elecsys assays for sFlt-1 and PlGF on an electrochemiluminescence immunoassay platform Cobas analyzer . Concentrations of cord NT-proBNP, TGFβ, PlGF, and sFlt1 are presented as continuous variables . Troponin I was treated as a dichotomous variable, and concentrations above the technical detection limit (>0.017 ng/mL) were considered positive .t-test or Mann–Whitney U-test was also used. A significance level of 0.05 was used throughout.Data were analyzed using the IBM SPSS Statistics version 23 statistical package . The Shapiro–Wilk test of normality was performed for continuous variables. Continuous variables are presented as median (interquartile range) or mean ± standard deviation, as appropriate. For normally distributed variables, overall differences between study groups were examined using parametric analysis of variance (one-way ANOVA) followed by post hoc Bonferroni tests for pairwise comparison. Differences between study groups in non-normally distributed variables were analyzed using Kruskal–Wallis one-way ANOVA followed by post-hoc pairwise comparisons using the Dunn–Bonferroni approach. Categorical variables are presented as n (percentage %), and differences between the groups were compared using the appropriate chi-square test. When necessary and appropriate, Student’s p = 0.026); thus, NT-proBNP was analyzed separately according to delivery route. The remaining cord biomarkers were not affected by the delivery route, and no other confounders were identified.Analysis of baseline variables for possible confounders , identified an association between cesarean section and increased levels of NT-proBNP (cesarean section median 547.0 pg/mL (interquartile range 304.0–996.0) vs. vaginal delivery 893.0 pg/mL (488.5–1523.8), Logistic regression analysis adjusted by cardiac anatomy and delivery mode was performed, and receiver–operating characteristics (ROC) curves were constructed for cord blood biomarkers in the form of areas under the curve to investigate the presence of a cutoff value that might be predictive of outcome in those fetuses with expected biventricular outcome.n = 29) and poor (n = 16) cardiac outcome . Heart rate was similar in the three groups. The left shortening fraction was increased in the favorable cardiac outcome group of left-CHD and decreased in the poor cardiac outcome left-CHD compared to the normal heart group. The remaining functional parameters evaluated did not show significant differences between the three study populations. Cardiac morphological and functional evaluation in control, left-CHD with favorable and poor cardiac outcome fetuses are shown in Results of cord blood biomarkers in left-CHD and normal heart groups are presented in Logistic regression analysis and evaluation of ROC curves of concentration of cord blood biomarkers for the prediction of outcome in fetuses with expected biventricular repair, adjusted for cardiac anatomy and cesarean section, found that only sFlt1 was useful as an outcome predictor. The sFlt1ROC curve had an AUC of 0.848  with a cutoff value of 1520.7, having a specificity of 100% and a sensitivity of 72% for a favorable outcome . Cord blood cardiovascular biomarkers are differentially expressed according to the clinical outcome of left-CHD. Fetuses with left-CHD and favorable outcome showed an active cardiac remodeling biomarker profile, with an increase in TGFβ and Troponin I cord blood concentrations. Conversely, fetuses with left-CHD and poor outcome presented a compensatory and proangiogenic biomarker profile with increased NT-proBNP and decreased sFlt1 concentrations.Prior studies reported increased NT-proBNP concentrations in children with systemic right ventricle and in single ventricle CHD before completion of staged palliation ,43,44. APositive cord blood Troponin I was more frequent in left-CHD with favorable cardiac outcome than in fetuses with normal hearts or fetuses with poor outcome. Differences were not statistically significant, and these results must be interpreted with caution as the normal heart group presented higher positive rates of Troponin I than previously reported in healthy fetuses ,45,46. ITo our knowledge, this is the first study to evaluate cord blood concentrations of TGFβ in fetuses with CHD, showing increased TGFβ concentrations in left-CHD with favorable outcome. High levels of circulating TGBβ are usually associated with increased endothelial shear stress, secondary to abnormal fluid dynamics within blood vessels ,49. All Cord blood concentrations of PlGF were found to be modestly decreased in left-CHD compared to normal heart fetuses. However, sFlt1 was markedly decreased in the poor outcome group conferring a proangiogenic profile of PlGF and sFlt1. Such low levels of sFlt1 had not been described previously in pregnancy, and their cause is unclear. However, sFlt1 is down-regulated by hypoxia , and theFinally, cord blood sFlt1 was identified for the first time as a possible outcome predictor in fetuses with expected biventricular repair and may eventually help to identify cases at risk of an unexpectedly poor prognosis despite favorable anatomy. Naturally, due to the limited number of cases in this subgroup, confirmation in larger cohorts is required prior to clinical application. A larger number of cases might also demonstrate the utility of NT-proBNP or TGFβ in these patients in which a poor prognosis comes as a surprise.To the best of our knowledge, this is the first study to evaluate cord blood biomarkers in a specific set of CHDs and to evaluate TGFβ in the cord blood of fetuses with CHDs. It is also the first study to identify TGFβ and specially sFlt1 as potentially useful cardiovascular biomarkers in left-CHD.This is mainly an exploratory study, and therefore, the eventual clinical application of our findings will likely be distant. The main limitation of this (and other studies) is the limited number of cases that precludes the evaluation of these biomarkers in each specific type of CHD. Interpretation of results is also limited by the presence of mixed pathologies in the favorable and poor outcome left-CHD groups. Cord blood biomarker levels were analyzed after adjustment for possible confounders; however, additional confounders might exist. Additionally, levels of Troponin I in the cord blood of normal fetuses were higher than previously reported ,45,46, wThis study provides evidence of a differential biomarker profile in left-CHD according to its outcome. It opens new opportunities for improving prognosis prediction and potentially helping in prenatal monitoring, neonatal management, and parental counseling. If confirmed in future studies, these biomarkers could potentially be useful as a prognosis tool in prenatal or neonatal life. In addition, future studies are warranted to study cardiovascular biomarkers in different matrices such as amniotic fluid or maternal blood. Long-term multicenter studies might be able to include enough patients and allow specific evaluation and analysis of each individual type of left-CHD. Additionally, the investigation of these biomarkers in the cord blood of other CHDs might also yield interesting results.


Heart transplantation is the recommended treatment method for patients withadvanced heart failure that is refractory to clinical treatment. Due to theprogressive severity of these patients and the impossibility of performingthe transplant in a short term, there are mechanical circulatory assistdevices that can offer necessary hemodynamic support and clinical stabilityin the period preceding the heart transplant surgery. The present study aimsto address and describe the main devices used as bridges for hearttransplantation, as well as to analyze their advantages anddisadvantages.This work is a literature review, developed with scientific production in theperiod from 2010 to 2020, that focus on circulatory assist devices as abridge for heart transplantation.These devices are characterized as a bridge for transplantation. Short-termor temporary devices are those used for hemodynamic support to stabilize theindividual clinically in the presence of refractory cardiogenic shock. Andlong-term devices are indicated for stable patients with long-term strategicplanning.According to the present study, it is possible to observe that there is awide variety of devices available on the market, enabling the mostappropriate choice according to the patient’s need. It is estimated that about 1-2% ofthe population have HF, and approximately half of these individuals have reducedejection fraction.Heart failure (HF) is considered the main cause of cardiovascular hospitalization inBrazil and is a complex clinical syndrome, in which the heart is unable to pumpblood to supply the metabolic tissue demand or only in the face of high fillingpressure. This condition can be caused by structural or functional cardiac changesand is characterized by typical signs and symptoms, which result from reducedcardiac output and/or high filling pressures at rest or on exertion.HF may be due to an abnormality in systolic function, producing a reduction in strokevolume (systolic HF), or an abnormality in diastolic function, leading to a defectin ventricular filling (diastolic HF), determining typical and characteristicsymptoms in each type of failure. Also, HF can be classified according to theejection fraction , the severity of symptoms, and thetime and progression of the disease (different stages).The main classification for HF is based on the left ventricular ejection fraction(LVEF) - normal LVEF (≥ 50%), heart failure with preserved ejection fraction(or HFpEF), and reduced LVEF (< 40%), heart failure with reduced ejectionfraction (or HFrEF). In addition to these two classifications, there are patientswith an ejection fraction between 40 and 49% who recently came to be defined asheart failure with intermediate ejection fraction (or HFiEF) or mid-range (orHFmrEF).In the last three decades, there has been a great evolution in the treatment ofchronic HF, however, there is still an important limitation in the quality of lifeof these patients - a significant part of these patients develop refractoriness toclassical treatment and hospitalizations with death and readmission rates in thesix-month period around 50%,5. However, thedestination of the organ for transplantation implies ethical issues and scarceresources, prioritizing the individuals most likely to survive in the longterm. Although hearttransplantation is the recommended treatment in these cases of HF, it is a limitedprocedure, mainly due to the number of donors available and the recipient’scontraindications, such as pulmonary hypertension (PH) secondary to HF.Heart transplantation is the recommended treatment method for patients with advancedHF and refractory to conservative treatment, are: advanced HF and peak VO2 = 12 ml/kg/minute in patientsusing beta-blockers ; advanced HF and peakVO2 = 14 ml/kg/minute in patients intolerant to beta-blockers ; advanced HF in dependence on inotropic drugs and/or mechanicalcirculatory support ; advanced HF functionalclass III persistent and IV with optimized treatment in the presence of otherfactors of poor prognosis ; symptomaticventricular arrhythmias that are refractory to management with drugs, electricaldevices, and ablation procedures .The main indications for heart transplantation, according to the third Braziliancardiac transplantation guideline,9. It isdivided into seven categories, with patients in critical condition (INTERMACS 1 and2) configuring situations in which the perioperative risk for transplantation isvery unfavorable.The prognostic evaluation of the patient in the heart transplantation queue can bedone using the Interagency Registry for Mechanically Assisted Circulatory Support(INTERMACS) classification. Although it was not created to define criteria for thesurgery, it is useful in clinical and prognostic evaluations, when indicatingtherapies for advanced HF and/or cardiogenic shock. Mechanical circulatory assistdevices (MCAD) can be classified in several ways, such as length of stay (short orlong), type of implantation technique , and typeof flow (pulsatile or continuous). Short-term or temporary devices are those used forhemodynamic rescue in order to stabilize the individual clinically in the presenceof refractory cardiogenic shock. And long-term devices are indicated for stablepatients with long-term strategic planning. In Brazil, there are currently threelong-term devices available: HeartMate II®, Berlin Heart INCOR®, andHeartWare®.Due to the progressive severity of the patients and the impossibility of performingthe transplant in a short term, there are devices that can offer hemodynamic supportand clinical stability, necessary in the period preceding the heart transplantsurgery. These devices are characterized as a bridge for transplantationThe number of patients supported by long-term MCAD, especially as a bridge fortransplantation, is increasing because these individuals are progressively improvingtheir survival..However, there is a restriction regarding the prioritization of the use of MCAD as abridge for transplantation, and it should be directed to those individuals withcomplications, in the impossibility of changing the device: clinical deteriorationdespite the device, intractable infection related to the device, mechanicaldysfunction of the device, thromboembolic events, device thrombosis with hemodynamicimpairment, and recurrent ventricular arrhythmiasThis study aims to address the main devices used as a bridge for hearttransplantation, as well as to analyze their indications, complications,advantages, and disadvantages and answer the following question, which is thebest device to be used as a bridge for transplantation?This is a descriptive literature review study, developed with scientific productionfrom 2010 to 2020 indexed in the electronic databases Latin American and CaribbeanHealth Sciences Literature (or LILACS), PubMed®, and Scientific ElectronicLibrary Online (or SciELO), which focus on circulatory assist devices as a bridgefor heart transplantation. The systematic review answers a specific question anduses explicit and systematic methods to identify, select, and critically evaluatethe studies, to collect and analyze the data of those studies to be included in thereview.bridge for decision, is used in patients withclinical conditions that contraindicate heart transplantation, however, ifmodified, allow the patient to become a candidate for transplantation;bridge for transplantation, in this case the device canoffer hemodynamic support and clinical stability until the surgery is performed,in the context of the patient’s progressive severity and the unavailability ofthe transplant in a short period; and destination therapy, whenthe device provides hemodynamic support and clinical stability in a patient withrefractory HF, which has a contraindication for heart transplantation, thusenabling greater survival and better quality of life when compared to medicaldrug treatment,12.Currently, mechanical circulatory support systems are used in three situations,according to the guidelines of the European Society of Cardiology (or ESC) andthe Mechanical Circulatory Assistance Directive of the Brazilian Society ofCardiology: a .Traditionally, temporary MCAD are preferentially indicated in INTERMACS 1 and 2patients, however those patients classified as INTERMACS 3, who are dependent onhigh inotropic doses or at high risk of hemodynamic instability, can beconsidered candidates,14.Temporary or short-term MCAD  arecomm.In order to assist heart transplantation candidates who may require the benefitsof circulatory assistance, devices have been developed that will function forlong periods until a donor is obtained . During . The maindisadvantages were its size, the noise produced, the risk of infection andembolization, and its mechanical durability, estimated in just twoyears.The first generation of MCAD used pulsatile flow mechanisms through pneumaticpropulsion. The implantation was done in an infradiaphragmaticposition.The second generation of MCAD uses axial continuous flow systems. The blood ispumped through an impeller, with a small high-speed system, so there is no needfor valves. With this evolution, there was a decrease in the size and weight ofthe devices, noise reduction, and implantation surgery involving a more limitedarea, which enables implantation in patients with a smaller body area.The HeartMate III® is the latest third-generation long-life device, it isa centrifugal MCAD with an all-magnetic impeller. MOMENTUM 3  compared HeartMate III® withHeartMate II® and obtained promising follow-up data.1) The intra-aortic balloon (IAB), which has an aortic counterpulsationmechanism, increases the diastolic pressure at the root of the aorta,thereby causing an increase in coronary perfusion, reducing afterload with aconsequent increase in output around 15%. IAB is usually inserted bypuncture of the femoral artery and positioned in the descending thoracicaorta, immediately distal to the origin of the left subclavianartery.2) Extracorporeal membrane oxygenation (ECMO) is a temporary invasivemechanical support that provides partial or total cardiopulmonary supportfor patients in cardiogenic shock and/or acute respiratory failure. It canbe of two types: venous-arterial and venous-venous. It is a device withquick installation, applicable to most patients, and which reversescirculatory failure and/or anoxia quickly. The implant is done throughpercutaneous cannulation or direct by thoracotomy. In venous-venous ECMO,both drainage and blood infusion are made exclusively from the venoussystem; venous-arterial ECMO is a temporary mechanical support (one to 30days) for patients with potential functional recovery or as a bridge fordecision, transplantation, or long-term MCAD.3) TandemHeart™ is a device that pumps blood from the left atriumthrough a cannula inserted transseptally by an extracorporeal centrifugalpump into the arterial iliofemoral system. In this case, both theTandemHeart™ and the left ventricle (LV) are responsible for sendingthe flow to the aorta, that is, they work in parallel. TandemHeart™consists of a transseptal cannula, centrifugal pump, femoral arterialcannula, and console.Cannulation of the femoral vein is performed with a 21 F introducer fortransseptal puncture, and the cannula is positioned in the left atrium.Then, the cannulation of the femoral artery is performed with a 15 or 17 Fcatheter. The 15 F cannulas produce a flow rate of 3.5 L/min and the 17 Fcannula produces 5 L/min. Full anticoagulation of the patient is required,and the length of stay with the device is up to 30 days. It is important tonote that even after the device is removed, the patient remains withresidual atrial septal defect.4) Impella® consists of a continuous axial flow pump, which drawsblood from the LV into the aorta, that is, in this case, it works in serieswith the LV. There are three types of Impella® on the market today,the difference between them is the flow allowed - flow of 2.5 L/min(Impella® 2.5), 4 L/min (Impella® CP), or 5.0 L/min(Impella® 5.0). In Brazil, currently, the available model is theImpella® CP. Cannulation of the femoral artery is performed for theImpella® implant, followed by the retrograde passage of the devicethrough the aortic valve and the positioning of the microaxial pump in theascending aorta by fluoroscopy. Full patient anticoagulation is required.The length of stay with the device is five to seven days.5) CentriMag®  is acon.6) Berlin Heart EXCOR® is a pulvs. 11%pulsatile), in overall survival (58% vs. 24% in two years),functional capacity, and quality of life. HeartMate II® can be used both asa bridge for transplantation and as destination therapy for those patientswho have a contraindication to transplantation. The parameters of thisdevice are pump flow (in L/min), pump speed (in rpm), pulse index (PI), andpump power (in watts). The main parameter to regulate it is the pump speed.If the speed is very high, the LV is low in volume, which can lead todeviated septum and hemodynamic collapse . The power of thepump represents the energy needed to run the pump; if too high, it maysuggest obstruction or thrombus. Patients with this implanted device shouldbe kept under standard treatment for HF and anticoagulation, if withoutcontraindications.1) HeartMate II®  is acon.The main complications of this device are stroke or embolic events, bleeding,infection, arrhythmias, and hemodynamic collapse due to deviatedinterventricular septum. However, the main cause of morbidity and mortalityin these patients is dysfunction of the right ventricle (RV), since this isa left assist device only.2) HeartWare®  -Ventri.3) Berlin Heart INCOR® , as well.According to a study carried out in 2017 by the Department of Surgery atColumbia University in New York, the number of patients with long-termdevices as a bridge to transplantation, as well as the duration of theiruse, has been increasing in large proportion, as has the rate of survival[21].Even within the short-stay category, some devices allow their use for a longerperiod, as is the cases with ECMO and EXCOR® and, in some cases, withCentriMag®, which make them an appropriate choice for those individuals whowill remain waiting for a transplant for a long time. Other advantages of thesethree devices are a greater hemodynamic support, allowing large blood flows. Inaddition, CentriMag® has less thrombogenicity when compared to othershort-stay devices. The disadvantages in relation to these three MCAD is the needfor thoracotomy for their implantation, in the case of ECMO there is the option ofbeing done percutaneously.IAB has the advantage of being percutaneously implanted, however it has a restrictedflow of 0.5 L/min, and the permanence with the device is up to 72 hours; this MCADis reserved for acute cases that evolve with serious complications, such ascardiogenic shock, while TandemHeart™ and Impella® offer greaterhemodynamic support , both of which areinserted percutaneously. The length of stay with Impella® is very short, upto seven days, since the TandemHeart™ allows its use for up to 30 days,requiring full patient anticoagulation in both cases, which can be a disadvantage.Another disadvantage of TandemHeart™ is the residual interatrialcommunication after its removal.In the case of long-term MCAD, only three models are available for use in Brazil. TheHeartMate II®, being a second-generation device, has no valves and provides acontinuous flow with an axial mechanism, it is regulated through the flow speed,which should not be kept too high, due to the risk of thrombus formation. Inaddition, its assistance is exclusive to LV, for this reason its biggestcomplication that also becomes a disadvantage is the dysfunction of the RV.HeartWare® and INCOR® are third-generation devices, also offering acontinuous flow, but with a centrifugal mechanism. The advantage ofHeartWare® is the flow recording, which allows greater control over thedevice because it can be adapted to the patient’s needs. INCOR®, being asmall pump, is widely used in pediatric patients, in addition to the fact that it iseasily implanted in the patient and has only one cannula that is externalized fromthe individual.According to the present study, it is possible to observe that there is a widevariety of devices available on the market, enabling the most appropriate choiceaccording to the patient’s need. Short-stay devices are still the most used as abridge for transplantation, while long-stay devices are preferred as a bridge fordecision and/or destination therapy.From the graphical analysis of the use of the devices, it is possible to verify thateven though they are less used as a bridge for transplantation compared toshort-term devices, long-term devices have a better long-term result and a higherpost-transplant survival rate. Among long-term devices, HeartWare® proved tobe the best option, as it is a third-generation device and allows for flowrecording, and therefore offers greater control and adaptation to the user’sneeds.


No relevant changes were seen in the other echocardiographic parameters. (4) Conclusions: six months of treatment with GLP-1 RAs dulaglutide or semaglutide leads to an improvement in the LV GLS in subjects with DM2 with and high/very high risk for ASCVD or with ASCVD. Further studies on larger populations and with a longer follow-up are warranted to confirm these preliminary results.(1) Background: Glucagone-Like Peptide-1 Receptor Agonists (GLP-1 RAs) (GLP-1 RAs) are incretine-based medications recommended in the treatment of type 2 Diabetes Mellitus (DM2) with atherosclerotic cardiovascular disease (ASCVD) or high or very high cardiovascular (CV) risk. However, knowledge of the direct mechanism of GLP-1 RAs on cardiac function is modest and not yet fully elucidated. Left ventricular (LV) Global Longitudinal Strain (GLS) with Speckle Tracking Echocardiography (STE) represents an innovative technique for the evaluation of myocardial contractility. (2) Methods: an observational, perspective, monocentric study was conducted in a cohort of 22 consecutive patients with DM2 and ASCVD or high/very high CV risk, enrolled between December 2019 and March 2020 and treated with GLP-1 RAs dulaglutide or semaglutide. The echocardiographic parameters of diastolic and systolic function were recorded at baseline and after six months of treatment. (3) Results: the mean age of the sample was 65 ± 10 years with a prevalence of the male sex (64%). A significant improvement in the LV GLS (mean difference: −1.4 ± 1.1%;  According to the International Diabetes Federation (IDF), diabetic individuals comprise almost 9% of the entire world’s population . MoreoveGlucagone-Like Peptide-1 Receptor Agonists (GLP-1 RAs) (GLP-1RAs) are incretine-based glucose-lowering medications widely used in the treatment of Diabetes Mellitus type 2 (DM2) ,10. BeyoWe conducted an observational, perspective, monocentric study in consecutive patients with DM2 to assess the effects of GLP1-RAs semaglutide and dulaglutide on cardiac function. The Inclusion criteria were: a diagnosis of DM2 and high or very high risk for cardiovascular (CV) disease or with an evident atherosclerotic cardiovascular disease (ASCVD); age ≥ 18 years; GLP-1 RAs naïve. The exclusion criteria were: contraindication for the prescription of GLP-1 Ras; previous treatment with anti-diabetic drugs or treatment with stable doses of metformin for at least 3 months; permanent atrial fibrillation or rhythm disorders; the presence of prosthetic valves; cancer cachexia; pregnancy and/or breastfeeding. Written informed consent was obtained from each participant before enrolment. The study was approved by the local ethics committee and conducted according to the principles of the revised Declaration of Helsinki.A preliminary screening visit was performed at the Diabetology Clinic of the Internal Medicine Unit of our tertiary hospital to assess the eligibility of patients, according to the criteria previously provided, and to obtain the informed consent. The demographic and anthropometric data , the presence of CV risk factors , drugs assumption, comorbidity and laboratory data  were collected in a paper case report form. Then, the data were recorded in an electronic spreadsheet by two investigators. After the enrolment, subcutaneous dulaglutide (1.5 mg or 0.75 mg weekly) or semaglutide (0.5 or 1.0 mg weekly) was prescribed.Each patient underwent echocardiographic exams at baseline, before the initiation of GLP-1 RA, and in the follow-up, after 6 months of treatment. The echocardiographic examination was performed in a dedicated echocardiographic laboratory in the outpatient Cardiologic Clinic of the same hospital, using Canon Aplio i700  by a cardiologist trained in echocardiographic imaging (with at least 15 years of experience) and according to the recommendations stated by the American Society of Ecocardiography (ASE) and the European Society of Cardiovascular Imaging (EACVI) . Before The endpoint of the study was to assess cardiac functional changes by echocardiography and, in particular, by GLS-STE, comparing the data at the baseline evaluation with the 6-month follow-up. Due to the explorative purpose of the study and the absence of previous data regarding the effects of dulaglutide and semaglutide on the endpoints analysed, a sample size determination was not performed. t-test for paired samples in cases of normally distributed data. For non-normal distributed variables, a Wilcoxon signed-rank test was used. Categorical variables were expressed as percentage values and compared by a X2 test or Fisher exact test, when appropriate. Furthermore, the association of the relevant baseline clinical variables with the mean difference of LV GLS after 6 months of GLP-1RAs treatment was explored. For continuous baseline variables, the Pearson’s or Spearman’s correlation coefficient was used, when appropriate. Baseline categorical variables were explored by point-biserial correlation A p value < 0.05 was set for statistical significance.All of the statistical analyses were performed using the Statistical Package for Social Sciences version 25 . Continuous variables were expressed as mean and standard deviation (SD) or median and interquartile range (IQR), when appropriate. The normal distribution of each variable was evaluated with the Kolmogorov-Smirnov test with Lilliefors correction. Differences in the values of the explanatory variables were compared by a p < 0.001) improvement in the LV GLS, with a mean value tending towards the normal range (19.5 ± 2.1%)  . No releTo the best of our knowledge, this is the first clinical study that has sought to evaluate the effect of GLP-1RAs semaglutide and dulaglutide on cardiac function by employing echocardiography and, in particular, STE in a cohort of consecutive DM2 patients with ASCVD or high or very high CV risk. The main results of the current analysis are that myocardial contraction, as assessed by GLS-STE, significantly improved after six months of GLP-1RAs semaglutide and dulaglutide therapy. Several CVOTs pointed out the cardioprotective role of these drugs ,15,16,172+ mishandling and mitochondrial dysfunction, which may play a crucial role in the earliest stages of DCM [Although there is a lack of a universally accepted definition, diabetic cardiomyopathy (DCM) is defined as the presence of ventricular dysfunction in absence of hypertension, CAD, congenital or valvular heart disease and may evolve towards overt heart failure ,27,28. Ds of DCM ,37.Several preclinical studies on animal models and clinical studies have demonstrated that GLP-1 and its analogues exert several beneficial actions on the cardiovascular system ,42,43,44GLS-STE represents an innovative technique for the evaluation of myocardial function ,22. NumeIn general, because of the heterogeneity of the study designs and the different pharmacological properties, any head-to-head comparison between different GLP-1 RA analogues should be interpreted cautiously. Therefore, further studies in larger populations and with a longer follow-up duration are needed to better elucidate the effect of these drugs on cardiac function.This study has some limitations. First, the reduced sample size led to weak statistical power. The identification of a difference between the baseline and after six months LV GLS requires further studies with a larger sample size to confirm these results. The second limitation is the absence of a control group and the lack of blinding, which may have led to bias in the evaluation of the echocardiographic parameters during the follow-up.In the present study, we observed that six months of treatment with GLP-1 RAs dulaglutide or semaglutide leads to an improvement of LV GLS in subjects with DM2 with a high or very high risk for ASCVD or with ASCVD. Accordingly, these antidiabetic drugs should be preferred in this setting of subjects in order to prevent the development of DCM. Further studies on larger populations and with a longer duration of follow-up are warranted to confirm these preliminary results.


It is characterized by prominent ventricular trabeculations, intratrabecular recesses and a bi-layered myocardium, composed of compacted and noncompacted layers.,2 Left ventricular noncompaction may be an isolated finding or associated to other cardiomyopathies, metabolic disorders and congenital heart diseases. It is believed to result from failure of ventricular compaction in the embryogenic phase, with increasing evidence of a genetic component.Left ventricular noncompaction (LVNC) is a relatively new and heterogeneous cardiomyopathy, first reported by Chin et al. in 1990.Since its first description, much has been learned about this disease, but there are some limitations for its diagnosis. Cardiac magnetic resonance imaging is considered the gold standard for diagnosis of LVNC, but echocardiography remains the first line imaging modality due to its availability and cost-effectiveness. 3D echo provided more detailed left ventricle morphology analysis and 3D echo color Doppler demonstrated ventricular flow within the intraventricular recesses. Strain analysis by speckle tracking echocardiography (STE) evidenced global longitudinal strain = -17% , probably related to an incipient systolic dysfunction not shown by evaluation of left ventricular ejection fraction in 2D echo  showed increased left ventricular trabeculation in the apical segments of lateral and anterior walls, and a noncompacted myocardium/compacted + noncompacted myocardium ratio of 0.33, compatible with LVNC, according to Chin´s criteria. 2D echo .This case illustrates echocardiographic modalities for LVNC diagnosis. 3D echo and STE are technologies that may play an incremental role in evaluation of LVNC but need further investigation and validation.


Here, we present a case with a pacemaker due to an atrioventricular (AV) block 2 Mobitz type, in whom a gating failure resulted in a relevant underestimation of cardiac function in myocardial perfusion scintigraphy. A set of quality control steps for gating errors is proposed. Myocardial perfusion scintigraphy (MPI) is an established tool in the diagnosis and prognosis of ischemic disease. Apart from perfusion, ECG-gated MPI provides information on cardiac function. Importantly, regional and global systolic left ventricular (LV) function is a powerful prognostic factor on its own.A female patient  with a high cardiovascular risk profile and progressive dyspnea was referred to our department for evaluation of suspected ischemic heart disease. She had been diagnosed with cerebral and peripheral vascular disease, diabetes mellitus type II, arterial hypertension, hypercholesterolemia, and nicotine consumption. A two chamber pacemaker due to AV-Block 2 type Mobitz was implanted 25 months ago. A recent echocardiogram report described normal regional and global systolic LV function.Pharmacological stress was performed with a 47.6 mg adenosine infusion over 5 minutes (0.14 mg⋅kg⋅min) while monitoring the patient with a 12-lead ECG (diagnostic ECG). Initial heart rate was 80 bpm, blood pressure 110/70 mmHg, which increased in 2.5 minutes to 120 bpm when 180 MBq Tc-99m-MIBI Sestamibi were injected. After 107 minutes, the patient underwent the first ECG-gated SPECT acquisition for 15 minutes, 18 minutes later, 534 MBq Tc-99m-MIBI Sestamibi were injected in rest followed with a delay of 15 minutes for the 5 minutes SPECT scan. Both scans were acquired on a D-SPECT camera  in identical upright positions. The MPI acquisition was ECG gated using a 3-lead cardiac triggering monitor . This monitor detects the R-waves in the ECG and sends them as binary pulses to the D-SPECT system for cardiac cycle-counts synchronization. The cardiac cycle was divided into 8 gates.QGS/QPS package  was used to MPI visualization and gated MPI analysis: automatic measurement of LV end systolic and end diastolic volumes , and corresponding ejection fraction (EF), and wall motion abnormalities assessment. The analysis was performed using the 17-myocardial AHA segmentsMPI at stress and rest showed a reduced uptake in the area of apex, indicating either a scar or a breast attenuation artifact. The assessment of LV global and regional function showed a severe dysfunction at stress and rest (ejection fraction below 30%) with a severe global hypokinesia Figure .Figure 1As these results were inconsistent with the clinical impression and the echocardiogram, concerns were raised by a physician. Already at first glance, the ECG-gated SPECT-based LV volumes curves Figure  show twoThis finding suggests that the delineation of the cardiac cycle was incorrect: the CTM would have wrongly triggered after the detection of intracycle waves, instead of the R-waves. Particularly, the ECG of the patient recorded an elevated T-wave that was wrongly detected for an R-wave Figure . Then, sInterestingly, the initial attempt to select only one of these peaks still did not solve the problem, as discussed in the following: due to the intracycle “pseudo R-waves” detection, no matter what beat rejection window used, the true heart rate could not be set in the beat histogram for ECG-gated image reconstruction. This disabled a reliable global and regional LV function assessment.Nevertheless, in order to estimate LV volumes and corresponding EF, we manually integrated the results from the ECG-gated series reconstructed from both peaks. As the triggering split the cardiac cycle virtually into two overlapping parts, a combined LV volume curve was constructed from the two ECG-gated scans Figure . ConsequSince the incorrect identification of the “true” R-wave led potentially to a misdiagnosis it is important to highlight checkpoints and solutions to avoid this error since no “correct” beat histogram can be selected.The following quality control should be done at the step of data acquisition. First the heart rate on the ECG system of the imaging device should be compared with that on the diagnostic ECG device, ensuring similar values. Second, quality of the trigger signal should be checked with a special attention in the case of an abnormal ECG , and settings should be adjusted if needed (e.g., lead change or specific features of the ECG such as a p-lock function activation for this particular deviceWe describe the clinically relevant impact of synchronization failure on assessment of cardiac contractile function in myocardial perfusion scintigraphy. Such gating errors can result in underestimation of regional and global LV function, especially in patients with pacemakers. A quality control of the gating process during myocardial scintigraphy is essential.