Type 2 diabetes (T2DM) is a major risk factor for myocardial infarction. Thrombus aspiration was considered a good way to deal with coronary thrombus in the treatment of acute myocardial infarction. However, recent studies have found that routine thrombus aspiration is not beneficial. This study is designed to investigate whether intracoronary artery retrograde thrombolysis (ICART) is more effective than thrombus aspiration or percutaneous transluminal coronary angioplasty (PTCA) in improving myocardial perfusion in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).IntraCoronary Artery Retrograde Thrombolysis (ICART) vs. thrombus aspiration or PTCA in STEMI trial is a single-center, prospective, randomized open-label trial with blinded evaluation of endpoints. A total of 286 patients with STEMI undergoing PPCI are randomly assigned to two groups: ICART and thrombus aspiration or PTCA. The primary endpoint is the incidence of >70% ST-segment elevation resolution. Secondary outcomes include distal embolization, myocardial blush grade, thrombolysis in myocardial infarction (TIMI) flow grade, and in-hospital bleeding.The ICART trial is the first randomized clinical trial (RCT) to date to verify the effect of ICART vs. thrombus aspiration or PTCA on myocardial perfusion in patients with STEMI undergoing PPCI.https://www.chictr.org.cn/], identifier [ChiCTR1900023849].[ Patients with type 2 diabetes (T2DM) are at high risk and have a poor prognosis of myocardial infarction, especially after ST-segment elevation myocardial infarction (STEMI). STEMI is due to plaque rupture leading to intracoronary thrombosis, thus blocking the coronary artery , 2. The At present, methods of opening occluded vessels include intravenous thrombolysis, primary percutaneous coronary intervention (PPCI), and emergency coronary artery bypass grafting (CABG) , 8. The Primary percutaneous coronary intervention is still the best way to treat acute myocardial infarction because of its simple operation and exact effect . ThrombuThe sequence of continuous thrombosis is white thrombus, mixed thrombus, and red thrombus. The white thrombus in the head is mainly composed of platelets. The red thrombus at the tail end is mainly composed of red cells within the fibrin network . Accordichictr.org.cn (ChiCTR1900023849).The ICART trial is a single-center, prospective, randomized controlled trial with a blinded evaluation of endpoints . A totalAll consecutive STEMI patients who are ready to receive primary PCI are suitable for inclusion. The inclusion criterion includes: (1) STEMI with chest pain lasting 30 min to 12 h; (2) older than 18 years old; (3) volunteered and signed informed consent. The exclusion criteria includes: (1) active peptic ulcer; (2) severe hepatic or renal insufficiency; (3) pregnancy; (4) uncontrolled hypertension; (5) rescue PCI after thrombolytic therapy; (6) unable to sign informed consent; (7) less than 18 years old; (8) left main coronary artery disease; (9) cardiogenic shock; (10) mechanical complications after myocardial infarction ; (11) recent history of major surgery, trauma, hemorrhagic disease, cerebrovascular accident, or thrombocytopenia; (12) previous history of CABG; (13) other obvious abnormal signs, laboratory tests, and clinical diseases. According to the judgment of the clinician, the patients are not suitable for the study.As we previously described , visualiThe flow diagram for the ICART system is shown in Before PCI, ICART or thrombus aspiration is decided according to the grouping. Thrombus is aspirated by the Export aspiration catheter  as previously described . FinallyPatients are given a loading dose of aspirin (300 mg) and ticagrelor 180 mg) or clopidogrel (600 mg), and are diagnosed STEMI by electrocardiography. It’s up to the operator to decide whether to use heparin or bevaludine for anticoagulation. In the setting of STEMI, radial access is preferred. In patients with radial artery pathways, sheaths are pulled out immediately following the PCI procedure. The femoral approach is reserved for patients without the radial approach. Sheaths are exchanged immediately at the end of the PCI procedure by the Angio-Seal device . After PCI, tirofiban is used for 36 h. Then low molecular weight heparin is given for 1–3 days after tirofiban. According to the international guidelines, standard post PCI medication includes aspirin (100 mg), ticagrelor (90 mg bid), or clopidogrel (75 mg), beta-blockers, lipid-lowering drugs, and angiotensin converting enzyme inhibitors or angiotensin II receptor blockers , partial (30–70%), or absent (<30%) . Residual ST-segment deviation after PCI is counted as the sum of residual ST-segment depression and elevation in all leads . All ECGThe baseline, peri-, and post-procedural angiographic features will be recorded: the presence of thrombus, treatment of a non-culprit vessel during the same procedure, myocardial blush grade (MBG), thrombolysis in myocardial infarction (TIMI) flow grades, side branch occlusion, the presence of angiographically visible distal embolization, minimum lumen diameter, stent diameter, stent length, no-reflow, and slow flow. TIMI flow grades are evaluated according to the previously described method . The evaThe infarct size is estimated by serial monitoring of cardiac markers such as creatine kinase (CK), creatine kinase-MB (CK-MB), and troponin T. Blood samples are taken at baseline and 3, 6, 9, 12, 18, 24, and 48 h after PCI. Peak value, time to peak release as well as area under the curve are determined.The primary endpoint is to observe the probability of ST-segment resolution > 70% acquired before and 30–60 min after PPCI.Secondary endpoints include:1.Angiographic endpoints: TIMI flow grade, distal embolization, no reflow, slow flow, side branch occlusion, myocardial blush grade post-PPCI.2.Electrocardiographic end points: residual ST-segment deviation 30–60 min after primary PCI.3.Enzymatic infarct size.4.Mortality and Major Adverse Cardiac Events: All-cause death, cardiogenic death, cardiogenic shock, reinfarction, revascularization of target vessels, malignant arrhythmia, NYHA class IV heart failure, stent thrombosis, and myocardial infarction rehospitalization are to be registered at 30 days and 1 year.Safety endpoints consist of in-hospital hemorrhagic and stroke complications.Furthermore, the primary and secondary endpoints will be analyzed in a preset subgroup, which is defined as:1.Age (<65 vs. >65 years)2.Gender3.Smoker4.Diabetes mellitus5.ST-segment resolution6.Number of diseased vessels (multi-vessel vs. single vessel)7.Proximal lesions8.Infarct-related artery [left anterior descending artery (LAD) vs. non-LAD]9.Bivalirudin10.Ischemic time (<3 vs. >3 h)11.Initial TIMI thrombus grade12.Angiographic presence of thrombus13.Intra-aortic artery balloon pump14.Left ventricular ejection fraction15.Type of P2Y12 inhibitor16.Killip class17.Symptom onset18.Pre-procedural TIMI flow19.Post-procedural TIMI flow20.Post-PCI myocardial blush grade21.Pacing use.All-cause death, cardiogenic death, cardiogenic shock, reinfarction, revascularization of target vessels, stroke, malignant arrhythmia, NYHA class IV heart failure, bleeding complications, stent thrombosis, and myocardial infarction rehospitalization are to be registered at 30 days and 1 year. The follow-up information will be obtained from hospital records as well as by telephone follow-up with the patients and/or their relatives.Data and instrumental measurements will be collected from all subjects using an electronic data capture system . Data entry and management will be completed by an independent data administrator to guarantee data accuracy. Only the principal investigator could access the data. The final dataset can be acquired only by the principal investigator and the independent statistician. All procedures will comply with the confidentiality standards for medical data. All documents related to clinical trial implementation will be retained by the principal investigator. Important scheme modifications during this project will be communicated to the institutional review board, trial registry, investigators, trial participants, and the journal of publication. Management and analysis of data will be carried out by an independent expert statistician.It has been reported that the incidence of ST-segment elevation resolution >70% has been reported to be 56.6% in STEMI patients treated with thrombus aspiration . We hypoStatistical analysis will be carried out using the SPSS statistical software package , and the level of significant difference will be established at α = 0.05. The data analysis will be performed by an independent professional statistician who is blinded to allocation. Analysis of efficacy will include all participants who complete the whole study.t-test will be used; otherwise, the Mann-Whitney U test will be carried out. Regarding the primary and secondary endpoint measures, multiple logistic regression will be used to compare the differences. The mean and standard deviation values of these parameters will be reported.Descriptive statistics will be used to compare the baseline characters between ICART and thrombus aspiration or PTCA group. If the normality test is satisfied, the independent The ICART project is a single-center, prospective, randomized controlled trial to make clear whether ICART procedure is more effective than thrombus aspiration or PTCA in improving myocardial perfusion and reducing reperfusion injury in STEMI patients undergoing primary PCI. This is the first RCT trial to clarify the effect of ICART vs. thrombus aspiration or PTCA on myocardial perfusion in STEMI patients undergoing PPCI.The trial is currently in the recruitment phase. The current protocol version number is V1.0 from 14 June 2019. The start recruitment date is January 2022. The expected end date is December 2023.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.This study has been approved by the Ethics Committee Board of the Chinese PLA General Hospital, Beijing, China on 25 March 2014. Written, informed consent to participate will be obtained from all participants.MS designed this project in collaboration with JT, SZ, JW, and DL. MS also drafted this manuscript. DL, XZ, YG, WZ, YG, JW, JL, and GZ revised the manuscript critically. DL was also responsible for the study of some cases in another center. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


On Kaplan–Meier survival curves, QRS-T angle > 120°, increased serum concentrations of NT-proBNP and troponin I levels as well as greater NYHA or Ross scale were associated with the greatest risk of unfavorable outcome. The QRS-T angle appears to be a valuable component of 12-lead ECG interpretation, and might be helpful in outlining patients with the greatest cardiovascular risk. Additionally, serum biomarkers such as NT-proBNP (p = 0.003) and troponin (p < 0.001) are useful in outlining patients with the worst survival.Cardiomyopathies have a low prevalence in children and thus may lead to malignant ventricular arrhythmias or the progression of heart failure, resulting in death. In adults, the QRS-T angle derived from ECG has been associated with adverse outcomes in patients with hypertrophic and dilated cardiomyopathies. We aimed to assess the electrocardiographic parameters, including QRS-T angle, associated with adverse cardiac events in children with cardiomyopathies. Forty-two children with cardiomyopathies were included in this study: 19 with dilated cardiomyopathy, 17 with hypertrophic cardiomyopathy, and 6 with left ventricular non-compaction. Additionally, 19 control subjects were recruited. In terms of ECG parameters, the QRS-T angle was significantly greater among patients with adverse outcomes compared to patients without the end points of the study (133° vs. 65°,  Vectorcardiography (VCG) is a field of electrocardiography that describes the direction and magnitude of the electrical forces conducted between cardiomyocytes . The QRSIn adults with non-ischemic dilated cardiomyopathies, a greater QRS-T angle is a risk factor for ventricular arrhythmias, re-hospitalizations due to heart failure, and increased mortality ,3,4. A sIt is of note that ventricular tachycardia in children may also be caused by channelopathies. Models helpful in understanding the pathophysiology and treatment of SQTS are being developed . FurtherIn our study, we focused on hypertrophic, dilated and left ventricular non-compaction cardiomyopathies because they are the most common among children . We hypoIn this single-center prospective study, we included 42 children with cardiomyopathies: 19 with idiopathic dilated cardiomyopathy (DCM), 17 with hypertrophic cardiomyopathy (HCM) and 6 with left ventricular non-compaction (LVNC). Additionally, 19 healthy, gender- and age-matched subjects were recruited. z-score > 2 combined with reduced ejection fraction (<55%). Secondary causes such as: aortic stenosis, coarctation of the aorta, or anomalous coronary arteries were excluded in all patients .In the present study, we outlined electrocardiographic risk factors associated with unfavorable outcomes among patients with cardiomyopathies. In adults with both dilated and hypertrophic cardiomyopathy, a greater QRS-T angle has been associated with unfavorable outcomes ,3,4,6. SIn our study, increased QRS-T angle and QTc, as well as the presence of at least two pathologically inverted T waves were associated with MACE in children with DCM. In the scarce studies on children, QTc has been associated with unfavorable outcomes. Chen et al. found a relationship between increased risk of malignant arrhythmia and: longer QRS duration, abnormal T-waves, ST-segment depression, QTc, JTc intervals, and QT and JT dispersion . SimilarIn adult patients with idiopathic dilated cardiomyopathy, a relationship between greater QRS-T angle and mortality, risk of an ICD shock or rehospitalization due to heart failure had been observed, with cut-off values ranging between >90° and 152° ,4. In ouIn contrast to the study by Chen et al., we found no correlation between pathological T wave inversion in only one ECG lead and adverse outcomes . In our Meulen et al. reported that the serum biomarker NT-proBNP is associated with adverse outcomes in children with dilated cardiomyopathy . A similz-scores were associated with unfavorable outcomes. Correlations between QRS-T angle and echocardiographic parameters such as LVIDd and LVEF were also shown, suggesting that electrocardiographic changes reflect echocardiographic abnormalities and could be helpful in predicting adverse outcomes.Unsurprisingly, echocardiographic findings such as decreased left ventricular ejection fraction, shortening fraction and increased left ventricular end diastolic dimension have been associated with increased risk of mortality in pediatric dilated cardiomyopathy patients ,25,30. INinety-seven per cent of pediatric HCM patients have abnormalities in their ECG . HoweverInterestingly, patients with HCM with no MACE also had a significantly greater QRS-T angle than the control group. This is in agreement with a study by Cortez et al. on adults, in which greater QRS-T angle helped to identify patients with HCM . It seemIn terms of serum biomarkers, the serum concentration of NT-proBNP was significantly higher among HCM patients with adverse outcomes (2659 vs. 125 pg/mL). This corresponds to the findings by Kaski et al., who showed a relationship between increased NT-proBNP levels and HCM severity among pediatric HCM patients . Thus, wp = 0.06) in comparison with the group without MACE. This may be explained by the fact that the majority of patients with adverse outcomes had arrhythmia and the number of patients who presented with heart failure in this group was low. Increased troponin concentration might be associated more with heart failure progression than with arrhythmia. However, further studies on a larger number of patients are necessary to support this hypothesis.CMR plays a significant role in the diagnosis of hypertrophic cardiomyopathy as well as identifying the extent of myocardial fibrosis . Increasz-score. Thus, in patients with HCM, even though the QRS-T angle was greater among patients with MACE, no correlations between echocardiographic parameters or serum biomarkers were found. Therefore, the QRS-T angle seems to be a valuable parameter in assessing conduction abnormalities, despite their heterogeneous origin. It appears that an increased QRS-T angle may reflect both abnormal stretching of the myocytes and irreversible changes in the myocardium such as fibrosis. On one hand, Li et al. reported in adults a decrease in the QRS-T angle after medical treatment [Correlation analysis in the DCM group showed an association between the QRS-T angle and NT-proBNP as well as QRS-T angle and echocardiographic parameters such as LVEF or LVIDd reatment , suggestreatment . This prreatment . Thus, dSome limitations of the study can be outlined. Because this was a single-center study and the prevalence of cardiomyopathies in children is low, the included number of patients was limited. Thus, we encourage studies on a larger scale, because the QRS-T angle seems to be an easily obtainable but not well-explored parameter in the pediatric population.QRS-T angle appears to be a valuable addition to standard electrocardiogram (ECG) interpretation. It is associated with adverse outcomes in children with both dilated and hypertrophic cardiomyopathies. Furthermore, serum biomarkers such as troponin and NT-proBNP might also be useful in outlining patients at the highest risk of heart failure progression and death.


Over the past two decades, major technological developments and progress have been reached for all imaging modalities applied to clinical cardiology, from echocardiography to magnetic resonance, computed tomography, nuclear imaging, etc. All these advancements and achievements progressively aid in filling the numerous gaps present in the current knowledge in the clinical practice of cardiology, as well as those of the disappointing unmet needs and goals for helping each patient, starting with clinical history, physical examinations and the standard 12-lead electrocardiogram (ECG) as a first step.In this context, all cardiologists should be able to select the most appropriate imaging modality to solve each specific problem whilst aiming to avoid a standardized, undifferentiated sequential approach to the universe of available modalities without taking into account a preliminary detailed analysis and discussion in regard to which modality could be the most appropriate for each clinical situation and with which sequentiality, in a complementary step by step selective approach. Selected and appropriate indications should also help to overcome accessibility problems due to the uneven geographical distribution and availability of each technique for cardiology in different areas, often being in competition with other medical specialties for the access to each specific imaging modality.Journal of Clinical Medicine.This editorial would like to focus on the subject through the window of opportunity offered by the papers published last year in the Coronary artery disease (CAD) represents the most common cardiovascular disease, presenting with high morbidity and mortality. Historically, and following guidelines, patients with chest pain of suspected coronary origin have been assessed with functional tests capable of detecting the haemodynamic consequences of coronary obstructions and related prognosis through the depiction of electrocardiographic changes, myocardial perfusion defects or novel regional wall motion abnormalities under stress conditions . Recent Myocardial and pericardial disorders encompass hypertrophic, dilated, arrhythmogenic, infiltratory, restrictive, inflammatory and other diseases of different aetiologies. Multimodality cardiac imaging techniques are extremely helpful in the definition of diagnosis, the assessment of prognosis and for monitoring the evolving natural history of these disorders through the planning of adequate follow-ups and treatments ,6,7,8,9.Congestion is the main cause of hospitalization in patients with acute heart failure; however, its precise assessment with simple clinical evaluations remains elusive. The complementary assessment of clinical, natriuretic peptides and other laboratory parameters, together with echocardiographic and lung ultrasound scan information, can be implemented in clinical practice, allowing physicians to more precisely quantify pulmonary congestion in order to achieve a more complete temporal evaluation of the clinical picture, as well as to determine the prognostic power of each measurement or parameter .Heart failure patients frequently develop brain deficits that lead to cognitive dysfunction. There is an important interaction between the brain and heart that becomes crucial for survival in patients with heart failure. An emerging experimental role of the combined brain/heart magnetic resonance imaging evaluation has the capability of diagnosing brain/heart lesions at an early stage and, potentially, facilitating their treatment . AdditioAfter a negative left ventricular remodelling, consequent to acute myocardial infarction, characterized by an increase in LV volumes and a depression in LVEF, operative treatment options can be considered to achieve a LV volume reduction and shape reconstruction. Conventional surgical LV reconstruction through a full median sternotomy has evolved towards the use of an experimental hybrid transcatheter and less invasive LV reconstruction . A comprThe assessment of the right ventricular morphology and function has gained increasing attention due to the prognostic importance of RV dilatation and dysfunction in patients with various cardiac and pulmonary diseases. A real-time evaluation of the right ventricular morphology and function through the use of three-dimensional echocardiography, combined with RV pressure-volume loops, could be useful in estimating RV-pulmonary arterial coupling, as previously experimentally assessed in an animal model .The research assessment of left atrial function could be of clinical and prognostic relevance in restrictive cardiomyopathy and heart failure. A decrease in the left atrial reservoir strain, as assessed using CMR, has been shown to be independently associated with time to adverse events in patients with restrictive cardiomyopathy . A left Sarcopenia is a progressive and generalized disorder characterized by the accelerated loss of skeletal muscle mass, strength and functionality. It was found to be associated with an increase in morbidity and mortality in various conditions, such as cancer and orthopaedic and abdominal surgery . The useTwo-dimensional, three- dimensional and Doppler transthoracic and transoesophageal echocardiography are the first-line imaging modalities for the diagnostic and prognostic assessment of valvular heart disease (VHD), followed by cardiac magnetic resonance for tissue and flow characterization and the detection of myocardial and papillary muscle fibrosis ,20,21,22The use of a transcatheter edge-to-edge repair for the treatment of mitral regurgitation has markedly increased in the last few years ,23. The Staphylococcus aureus bacteraemia without an echocardiographic evaluation, either transthoracic and/or transoesophageal (TEE). The usefulness of PREDICT, POSITIVE, and VIRSTA scores to rule out infective endocarditis without echocardiography was assessed together with the secondary purpose of evaluating whether not performing an echocardiogram could be associated with higher mortality [Staphylococcus aureus bacteraemia patients [It is unclear whether the use of clinical prediction rules is sufficient to rule out infective endocarditis (IE) in patients with ortality . PREDICTortality . In patiortality . Not perortality . Furtherpatients . Besidespatients ,26,27, wpatients ,26,27. FAthlete’s heart refers to a wide spectrum of morphological and functional changes that occur in the heart and circulation of subjects practicing regularly physical activity, usually following a training program. When the morphofunctional changes associated with athlete’s heart are more relevant, they can overlap phenotypes mimicking structural cardiac diseases, including cardiomyopathies, valvular diseases, aortopathies, myocarditis and coronary artery anomalies. In these situations, a precise differential diagnosis is of paramount importance. This can be reached by applying an appropriate and selective approach to different imaging modalities, including rest and exercise stress echocardiography, speckle tracking echocardiography, cardiac magnetic resonance, computed tomography and nuclear scintigraphy ,29. In tMultimodality imaging is the basis for the diagnosis, follow-up and surgical management of congenital bicuspid aortic valve patients. The complementary role of transthoracic and transoesophageal echocardiography for valvular phenotyping and function, the measurement of thoracic aorta, exclusion of other aortic malformations, and assessment of complications such as infective endocarditis, aortic dilatation and dissection has been outlined ,32. In tThe relationship between pulmonary regurgitation and ventriculoarterial interactions in patients with the postearly repair of the Tetralogy of Fallot was studied by using a cardiovascular magnetic resonance (CMR)-derived wave intensity analysis . A correThe association of gestational age and echocardiographic markers as image modalities and levels of plasma N-terminal pro-B-type natriuretic peptides could help to predict the closure rate of a haemodynamically significant patent ductus arteriosus (PDA) . InfantsMultiple cardiac imaging technique tools have been developed for the assessment of the left atrium. Although transthoracic echocardiography is the most widely employed procedure for the calculation of atrial size and function (due to its ease of use and wide availability), transoesophageal echocardiography, cardiac magnetic resonance, computed tomography and electroanatomical mapping can all be very useful for the management of cardiac rhythm disorders of atrial origin . The mulEndovascular pulmonary vein isolation (PVI) has become an important strategy for rhythm control in patients with symptomatic atrial fibrillation. Transseptal access is a critical step of this procedure, and can result in potentially life-threatening complications. TEE guidance may allow for safe transseptal access to the left atrium in patients undergoing PVI .


Introduction: An elevated heart rate is associated with an increased risk of death or cardiac transplant in children with dilated cardiomyopathy (DCM). Whether heart rate is a clinical marker to address therapy, is poorly investigated in children.Aim: To investigate the relationship between heart rate reduction (HRR) and left ventricular ejection fraction (LVEF) in DCM, treated with carvedilol.Methods: This is a multi center retrospective analysis conducted on all children with DCM (aged <18 years) between 2013 and 2020, with LVEF <40% and treated with carvedilol. Carvedilol was up titrated to the maximal tolerated dose or to 1 mg/kg/day. Echocardiographic data on left ventricular function and dimension were collected. The relationship between HRR and LVEF, left ventricular end-diastolic (LVEDd) and end-systolic diameter (LVESd) was assessed before and after HRR with carvedilol, using regression analysis.Results: 100 patients were enrolled . The mean LVEF was 30.2 ± 10% before treatment and 43.7 ± 9.6% after treatment, at the maximum therapeutic dose (p < 0.0001). There was a positive relationship between HRR and increase in LVEF . A HRR of >20% correlated with an improvement in LVEF >13%. At 3 years follow up, HRR demonstrated a significant reduction of LVESd  LVEDd  and LVEF recovery up to 15% (p < 0.0001). No deaths or heart transplant occurred during follow-up.Conclusion: This study demonstrates that HRR is safe and improvement in LVEF is related to the degree of HRR. The magnitude of LVEF improvement was enhanced by a major reduction in HR. It provides evidence that HRR could be used as a clinical marker to treat HF in children. The beneficial effects of beta blockers in chronic heart failure (CHF), especially in adults, are well recognized and this class of drugs is currently recommended to improve prognosis Heart rate is one of the main markers of heart failure at any age . RecentlThe aim of this study is to investigate the relationship between heart rate reduction (HRR) and left ventricular function in pediatric patients in chronic heart failure, with DCM, treated with carvedilol.Data were reviewed retrospectively from hospital database from 2013 to 2019 of all consecutive pediatric patients affected by DCM and left ventricular (LV) dysfunction referred to Bambino Gesù Children Hospital, Rome, Monaldi Hospital, Napoli, and Centro Cardiologico Mediterraneo Taormina. DCM was defined by the presence of LV dilatation (>2 SD) and systolic dysfunction in the absence of abnormal loading conditions  or coronary artery disease sufficient to cause global systolic impairment . InclusiCarvedilol was up titrated starting from 0.1 mg/kg/dose BID to the maximum tolerated dose every 2–4 weeks and/or maximum dosage of 0.5 mg/kg/dose BID. The maximum tolerated dose was defined according to the onset of symptomatic hypotension and/or bradycardia (<60 bpm) .Data were collected for each patient at baseline, at maximum dose of beta-blocker and after 3 years. They included: gender, NYHA/Ross functional class, pharmacological treatment, blood pressure (BP), HR and echocardiographic parameters including LVEF, left ventricular systolic (LVESd) and diastolic diameter (LVEDd), time of follow up and outcomes including death and heart transplant (HT).To assess the functional capacity in children, we used the following reported Ross Classification: class I included patients with no limitations or symptoms; II: infants with mild tachypnea or diaphoresis with feeding or children with mild to moderate dyspnea on exertion; III: infants presenting growth failure and marked tachypnea or diaphoresis with feeding or children with marked dyspnea on exertion; IV infants or children with symptoms at rest . In patip-value was considered significant when ≤0.05.All statistical analysis was performed by SPSS Statistics 21 . Categorical variables are expressed as absolute numbers or percentages. Continuous variables are presented as mean value and standard deviation (SD). Chi square analysis and t-student test were used to compare categorical and continuous variable, as appropriate. Regression analysis was performed to correlate changes in HR with changes in echo parameters, results were graphically represented. p < 0.05) (p: 0.05). According to the age, we subdived all patients in four groups: < 1 year, between 1–5 years, 6–12 years, > 12 years <18 years. The analysis showed that there was a more pronounced effect of heart rate reduction in children below 1 year of age when compared to the group of 1–5 years  . No gend–5 years .p < 0.0001); after 3 years of follow up mean LVEF was 45.9 ± 10.2% (p < 0.0001), with an overall increase in EF of 15.7 ± 12.9% from baseline   .p = 0.08), with a reduction of around 4 ± 9 mm. Mean LVEDd at baseline was 46 ± 16 mm and 43,6 ± 16 mm at maximum carvedilol dose , with a delta reduction of 2.7 ± 5.8 mm. LVEDs and LVEDd at baseline and at achievement of the maximum dose differed significantly in correlation to HRR  (Mean LVESd was 38 ± 12 mm at baseline and 35 ± 11 mm at the maximum dose (ctively) .A HRR of >20% was positively related to an improvement in LVEF and to a reduction in LV diameters. No deaths or HT occurred during follow-up.No episodes of hypotension and/or bradycardia were recorded during follow up.p = 0.05). Interestingly, HRR was more pronounced in patients aged <1 year, with a significant difference when compared to the older groups (p = 0.04).No statistically significant relation in HRR have been found between gender at regression analysis  and with death or transplant  in children affected by DCM. An elevated HR was also associated to congestive HF, the need of anticongestive therapy, lower LVEF and greater LV dimension  with cardiac concerns reported less frequently by patients on ivabradine than placebo . Interestingly, a high inter-individual variability in response to ivabradine was observed. This study showed that the HR might be manipulated also in children (Recently the availability of ivabradine in pediatric formulation raised the question of the impact of the HR in pediatric population. In a randomized, double-blind, placebo-controlled, phase II/III trial in children with symptomatic chronic HF due to DCM, using ivabradine, a HR reduction >20% was considered as a therapeutic target . Ivabradchildren .In pediatric HF, this report, in addition to the Ivabradine trial, strongly suggests that HRR is important. The current dosing of beta-blockers is empirical and not guided by clinical markers other than when adverse effects occur. The HR is an easy clinical marker to guide therapy and the HRR correlates closely with improvement in ventricular function. It is important to notice, that it is crucial to differentiate acute from chronic phase. Because the detrimental effect on systemic vascular resistance, beta blockers are contraindicated in the acute phase. Signs and symptoms could lack of accuracy to differentiate between acute and chronic status. The use of natriuretic peptide helped to identify these settings and BNP levels have been used to rule out those in acute phase. Plasma concentrations of natriuretic peptides can help to understand the individual risk of the patient and address therapy.This analysis shows that it is possible to utilize a simple clinical marker in the management of chronic HF with therapy including carvedilol in an individualized manner to improve LV function. HRR correlates with improved ventricular function and so in children, HR should be considered a potentially modifiable clinical marker to maximise therapy.


Pregnancy-induced hypertension syndrome (PIH) is a common pregnancy syndrome that could cause varying degrees of maternal and fetal organic damage and even endanger their lives. This study aimed to investigate ultrasound of fetal cardiac function changes in PIH. Totally 40 cases of gestational hypertension admitted to Cangzhou Central Hospital between October 2018 and September 2019 were enrolled in the hypertension group, and 40 women with healthy pregnancies during the same period were assigned to the normal group. Ultrasound results showed that PIH was associated with a significantly higher fetal cardiac septal thickness, fetal left ventricular end-diastolic area and end-systolic area, fetal right ventricular end-diastolic area and end-systolic area, fetal left ventricular systolic fraction 1 (VSF1), fetal left ventricular systolic fraction 2 (VSF2), fetal right VSF1, and fetal right VSF2 versus healthy pregnancy. The PIH fetuses had significantly lower neonatal weights versus healthy fetuses. Newborns of hypertensive pregnancies have larger hearts, faster heart rates, increased cardiac contractility, and lower weights versus newborns of healthy pregnancies. Pregnancy-induced hypertension syndrome (PIH) is a common pregnancy syndrome that could cause varying degrees of maternal and fetal organic damage and even endanger their lives , 2. Its Due to the unknown etiology of PIH, the treatment mostly relies on spasm lysis, hypotension, diuresis, and timely termination of pregnancy according to its predisposition factors and pathophysiological changes. This disease seriously compromises maternal and child health and is one of the leading causes of morbidity and mortality in pregnant women and perinatal children. Therefore, early detection and assessment of fetal cardiac function are paramount to guide clinical assessment of the condition for further treatment . EchocarThe present study was conducted to compare the cardiac function of fetuses of PIH with those of normal pregnancy through ultrasound to investigate the diagnostic value of ultrasound for PIH on fetal cardiac function changes and its significance for clinical reference.Between October 2018 and September 2019, 40 cases of PIH admitted to our institution were assessed for eligibility and recruited in the hypertension group, and 40 women with healthy pregnancies during the same period were assigned to the normal group. All 80 cases in both groups were singleton fetuses with no malformations after examinations. The study was ethically approved by the Ethics Committee of Cangzhou Central Hospital (2018-JY225).It includes (a) patients with singleton pregnancies; (b) patients with PIH who met the diagnostic criteria of the syndrome in the hypertension group; (c) patients with normal communication skills; and (d) patients with knowledge and consent to the study content.It includes (a) patients with fetal malformations; (b) patients with fetuses with congenital heart disease; and (c) patients with abnormal liver and kidney functions.Fetal biparietal diameter, head perimeter, femoral length, amniotic fluid index, and placenta condition were measured.The fetal spine, liver, and gastric vesicles were identified as the left and right ventricles of the heart. The thickness of the diastolic interventricular septum (IVS) was measured under a four-chamber heart view. The left ventricular end-systolic perimeter and area , right ventricular end-systolic perimeter and area , and right and left ventricular end-diastolic perimeter and area  were measured as per the different phases of the heart and playback function.Ventricular systolic fraction 1 (VSF1) = (ventricular end-diastolic perimeter−ventricular end-systolic perimeter)/ventricular end-diastolic perimeter. Ventricular systolic fraction 2 (VSF2) = (ventricular end-diastolic area−ventricular end-systolic area)/ventricular end-diastolic area.s) and processed using independent samples t-test. The count data were expressed as  and analyzed using the chi-square test. Differences were considered statistically significant at P < 0.05.SPSS 20.0 was used for data analyses, and GraphPad Prism 8 was used for image rendering. The measurement data were expressed as (P > 0.05)  were comparable with those of the normal group  ( > 0.05) .P < 0.05). PIH exerts a greater effect on the right cardiac system than on the left cardiac system  , the FVSF2 was (0.38 ± 0.15), the RVSF1 was (0.24 ± 0.03), and the RVFS2 was (0.35 ± 0.08), while the above indicators were (0.13 ± 0.04), (0.20 ± 0.09), (0.16 ± 0.10), and (0.21 ± 0.14) in the normal group. The systolic fractions of both the left and right ventricles were significantly higher in the fetuses of the hypertension group versus those of the normal group ( < 0.05) .g and that of the newborns in the normal group was (3486 ± 589) g. PIH newborns showed significantly lower neonatal weights versus healthy newborns (P < 0.05) (The weight of the newborns in the hypertension group was (3036 ± 761)  < 0.05) .The results of the present study showed a significantly higher fetal ventricular systolic and diastolic perimeter and area and septal thickness in the hypertension group than in the normal group, which indicates that maternal hypertension in pregnancy may seriously compromise the fetal cardiac function. Meanwhile, PIH causes a greater impact on the fetal right heart system than the left heart system, suggesting a larger right heart system than the left heart system in fetuses of PIH , 11. In PIH is a syndrome specific to pregnant women , 17 and The PIH fetuses had significantly lower neonatal weights versus healthy fetuses. Newborns of hypertensive pregnancies have larger hearts, faster heart rates, increased cardiac contractility, and lower weights versus newborns of healthy pregnancies.


Electromechanical coupling in patients receiving cardiac resynchronization therapy (CRT) is not fully understood. Our aim was to determine the best combination of electrical and mechanical substrates associated with effective CRT.Sixty-two patients were prospectively enrolled from two centres. Patients underwent 12-lead electrocardiogram (ECG), cardiovascular magnetic resonance (CMR), echocardiography, and anatomo-electromechanical mapping (AEMM). Remodelling was measured as the end-systolic volume (ΔESV) decrease at 6 months. CRT was defined effective with ΔESV ≤ −15%. QRS duration (QRSd) was measured from ECG. Area strain was obtained from AEMM and used to derive systolic stretch index (SSI) and total left-ventricular mechanical time. Total left-ventricular activation time (TLVAT) and transeptal time (TST) were derived from AEMM and ECG. Scar was measured from CMR. Significant correlations were observed between ΔESV and TST , TLVAT , scar , and SSI , but not QRSd . TLVAT and SSI were highly accurate in identifying CRT response [area under the curve (AUC) > 0.80], followed by scar (AUC > 0.70). Total left-ventricular activation time (odds ratio = 0.91), scar (0.94), and SSI (1.29) were independent factors associated with effective CRT. Subjects with SSI >7.9% and TLVAT <91 ms all responded to CRT with a median ΔESV ≈ −50%, while low SSI and prolonged TLVAT were more common in non-responders (ΔESV ≈ −5%).Electromechanical measurements are better associated with CRT response than conventional ECG variables. The absence of scar combined with high SSI and low TLVAT ensures effectiveness of CRT.  A long total left-ventricular activation time (TLVAT) indicates slow myocardial conduction within the LV and negatively affects reverse remodelling after CRT.A long transeptal time reflects the presence of left-bundle branch block and is associated with reverse remodelling.A high systolic stretch index (SSI), an index of mechanical dyssynchrony, constitutes a favourable mechanical substrate for CRT.TLVAT, SSI, and scar burden are independent factors contributing to reverse remodelling.1 Nowadays, CRT can treat 25–30% of symptomatic HF patients (NYHA Classes II–IV) and it is recommended in the individuals presenting with electrical conduction delay characterized by QRS duration (QRSd) ≥ 130 ms and, most preferably, left-bundle branch block (LBBB). Despite these stringent selection criteria, the benefit of CRT varies considerably among the patients.2Over the last two decades randomized controlled trials showed that cardiac resynchronization therapy (CRT) creates a consistent benefit in selected patients with heart failure (HF).3 In daily clinical practice, the CRT candidate is routinely assessed using different modalities, such as electrocardiogram (ECG), echocardiography, and cardiac magnetic resonance (CMR).4 However, combining the information obtained from these diagnostic tools is problematic due to inaccuracy in matching of the data over space and time.5Recent studies indicate that mechanical discoordination parameters  provide valuable information on top of the conventional measures of electrical dyssynchrony, to identify the substrate for CRT.in vivo quantification of local mechanical deformations at exactly the same position and at the same time.6A technique that provides full electromechanical (EM) mapping is the NOGA-XP system . Beside regular electrograms along the endocardium, the measurement of the motion of the tip of the electrode at all positions provides It was the aim of the present study to use the NOGA-XP system to find the best combination of electrical and mechanical parameters associated with the echocardiographic response to CRT. To this purpose, we designed a two-centre, 6-month follow-up study, aiming at: (i) comparing the baseline EM characteristics between CRT responders and non-responders; (ii) evaluating the strength of the association between EM variables and the extent of reverse remodelling; and (iii) identifying the independent EM predictors of positive CRT outcome.n = 29, Lugano, Switzerland) and the Medical University of Silesia  between 2012 and 2018.Sixty-two patients with moderate to severe HF were prospectively enrolled in the study. All patients were referred for implantation of a CRT device at two centres, Istituto Cardiocentro Ticino 7; and/or intraventricular conduction delay. Exclusion criteria were: presence of coronary artery disease requiring revascularization; acute coronary syndrome <3 months prior to study enrolment; implantation of pacemaker; presence of implantable cardioverter-defibrillator; left-ventricular thrombus or aneurysm; severe aortic stenosis, renal failure (glomerular filtration rate <30 mL/min/1.73 m2); history of neoplasm; bleeding diathesis; HIV, hepatitis B virus, hepatitis C virus infection; pregnancy; and contrast allergy.Inclusion criteria were: age >18 years; ischaemic, and non-ischaemic cardiomyopathy; sinus rhythm; QRSd > 120 ms; QRS morphology of LBBB  <35%.At baseline, each patient underwent standard 12-lead echocardiography, CMR examination, standard 2D echocardiography and NOGA-based invasive EM study prior to CRT implantation. Left-ventricular volumes and function were reassessed 6 months after the implantation by means of standard 2D echocardiography to evaluate clinical outcome of CRT.6 The catheter recorded unipolar and bipolar electrograms at 1 kHz, as well as the position of the contact point at 100 Hz. Care was taken to cover the whole endocardial cavity. The acquired electrical and mechanical signals at different positions were aligned over time by the system with respect to the simultaneously recorded 12-lead surface ECG.Electromechanical mapping of the left endocardial cavity was performed using the NOGA-XP system  and a conventional 7 Fr deflectable-tip mapping catheter . The mapping and navigation systems have been described in detail elsewhere.Figure 1A). For the mechanical contraction, local area strain was computed following a procedure previously described.4 The first strain peak was used to identify the time-to-peak shortening (TPS) interval . From the processed signals a set of EM measurements were derived:The acquired data sets were subsequently imported and processed in MATLAB  to obtain a set of EM measurements to be investigated as factors associated with the procedural outcome. Data were filtered removing all those points showing non-physiological motion  or belonging to the papillary muscles and protruding inside the reconstructed cavity. For the electrical activity, the local time of depolarization (TD) was identified in correspondence of the steepest change of the local unipolar electrogram in a time window belonging to the QRS complex ;EM coupling, defined as the Pearson’s correlation coefficient Figure 1A);transeptal time (TST), a measure of interventricular delay, defined as the time interval between the onset of the QRS complex and the earliest LV endocardial depolarization ;total left-ventricular activation time (TLVAT), a measure of intra-LV conduction delay, determined as the time interval between the earliest and latest LV endocardial depolarization ;total mechanical activation time (TLVMT), a measure of mechanical dyssynchrony, determined as the time interval between earliest and latest negative peak of area strain  of the area strain curve during the ejection phase.9systolic stretch index (SSI), a measure of mechanical discoordination, defined as the sum of the posterolateral pre-stretch and the septal rebound stretch  at Cardiocentro Ticino and a 1.5 T scanner at Medical University of Silesia , equipped with standard torso coil. A stack of delayed enhancement short-axis images covering the whole long axis were obtained 7–12 min after the intravenous bolus injection of gadolinium (0.2 mmol/kg body weight). The epicardial and endocardial boundaries were manually traced in each slice and then scar was automatically identified using the full-width half-maximum criterion.Echocardiographic examinations were performed using iE33  and Epiq 7G  ultrasound systems. Patients were evaluated in the left lateral decubitus position and images acquired from standard parasternal, suprasternal, and apical windows. Data were digitally recorded and analysed offline by a single observer for the two centres. Left-ventricular end-systolic and end-diastolic volumes, and ejection fraction were obtained using the modified biplane Simpson method.Left-ventricular (LV) remodelling at 6-month follow up was measured in terms of per cent change in end-systolic volume with respect to the baseline value (ΔESV). Significant response to CRT was defined as a reduction in ESV ≥15% at 6-month evaluation.U test or Fisher’s exact test for continuous and categorical variables, respectively. The strength of the association between EM variables and the extent of remodelling at 6-month follow up (ΔESV) was quantified by Spearman’s correlation coefficient (rho). Area under the curve (AUC) was determined from receiver operating characteristic (ROC) analysis to determine the ability of the baseline EM variables to classify the response to CRT. The association between single factor and CRT response was also evaluated using binary logistic regression and expressed in terms of odds ratio. Factors significantly associated with CRT response at univariate analysis were entered in a stepwise multivariate binary logistic regression. A P-value of <0.05 was considered statistically significant. Statistical analysis was performed using SPSS .Data are expressed as median (first to third quartiles), or as absolute count (and per cent frequency), as appropriate. Comparison between groups has been evaluated by means of Mann–Whitney Table 1. The patients in the two centres were similar in terms of clinical characteristics, except for a larger prevalence of ischaemic cardiomyopathy and LBBB in Centre #2.Out of the 62 enrolled patients, 4 patients did not undergo CRT, 2 were excluded for poor acoustic window either at baseline or at follow-up echocardiographic evaluation and one patient did not show up at follow up. The baseline clinical characteristics of the remaining 55 patients, overall as well as separately for the two centres, are summarized in Endocardial mapping (approximately 30 min/patient) and CRT implantation were feasible in all patients with no peri- and post-procedural complications. For each patient, 225 (179–251) unique LV endocardial sites were mapped and used for post processing. Mean fluoroscopy and radiation dose were 22 min 26 s and 322.8 mGy, respectively.Cardiac resynchronization therapy resulted in a significant reduction of EDV [from 230 (180–274) to 196 (145–250) mL] and ESV [from 170 (131–205) to 112 (81–170) mL], and an increase in LVEF [from 25 (23–30)% to 39 (32–46) %]. With respect to the endpoint, the observed reduction in ΔESV was 34 (7–47) mL, with 39 patients (71%) experiencing a reduction in ΔESV(%) ≥15%, and thus classified as responders.Table 2 shows that at baseline responders had lower scar burden, longer TST, shorter TLVAT, and higher SSI values than non-responders. Conversely, QRSd, LVEF, and TLVMT where similar between the two groups.Table 3), while LVEF, EM coupling, QRSd, and TLVMT did not significantly relate to reverse remodelling. Importantly, higher TST and SSI values were associated with a larger reduction in ESV, whereas larger scar burden and more prolonged TLVAT related to a lower extent of remodelling.Significant correlations were observed between %ΔESV and TST, TLVAT, scar burden, and SSI (Table 3. The best discriminatory capability was found for TLVAT and SSI (AUC > 0.80). Scar burden and TST moderately predicted the response to CRT .The performance of EM measurements in identifying responders is shown in Figure 2). Of note, regression analysis performed on the subgroup of patients with any scar showed a poor, although significant, correlation between TLVAT and the per cent scar burden , suggesting that the slow intraventricular conduction can only be marginally explained by the presence of scar.Multivariate logistic regression analysis identified TLVAT, scar burden, and SSI as independent factors associated with significant response to CRT . Subjects with high SSI and short TLVAT all responded to CRT with a median reduction in LVESV of ∼50%. Conversely, most of the subjects with prolonged TLVAT and low SSI fell in the non-response area (median reduction in LVESV ∼5%). Intermediate reductions on LVESV were observed in the subgroups with low SSI and TLAVT and with high SSI and TLVAT.Focusing on the EM variables TLVAT and SSI, patients were subdivided into subgroups according to the median values of these variables in the study population (The main findings of the present study are that: (i) of the electrical measures, TLVAT and TST have opposite relationships with reverse remodelling, (ii) a large SSI value constitutes a favourable mechanical substrate for CRT; (iii) TLVAT, SSI, and scar burden are independent factors contributing to reverse remodelling.11 The latter also supports the other main finding of the present study, that TST relates to reverse remodelling, because a long TST, with RV activation preceding LV activation, is a specific feature of LBBB.A novel finding of the present study is that a long TLVAT seems to hamper reverse remodelling. This seems at odds with the idea that longer QRSd enhances CRT response. However, more recently, LBBB morphology rather than QRSd was found to be predictive of CRT response.12 Therefore, these discrepant findings are likely due to the difference in definitions and therefore we deliberately called this variable TLVAT, expressing that the mapping covered the entire LV endocardium.In contrast, TLVAT describes the time required for the electrical impulse to travel along the entire LV endocardium. The mean TLVAT values of 81 and 112 ms in responders and non-responders, respectively, are considerably larger than can be expected to be caused by conduction along the Purkinje fibres. Therefore, TLVAT in these patients probably reflects the impulse conduction through the LV working myocardium. Prolongation of this impulse conduction may be caused by fibrosis or other kinds of electrical uncoupling. These poor conduction properties persist during biventricular pacing, therefore a long baseline TLVAT likely translates into a slower conduction during pacing, hampering CRT effectiveness. These findings appear in conflict with the positive correlation between reverse remodelling and LV activation time, calculated as QRSd minus RV activation time (time until the first notch in the QRS complex of the LBBB morphology on a surface ECG).13 We propose that a long TST reflects LBBB and a short TLVAT good LV conduction properties and that also enhance relatively fast activation during biventricular pacing. Therefore, patients with a high TST/TLVAT ratio are most likely patients with a proximal LBBB.More recent mapping studies have shown that in two-thirds of LBBB patients, the location of the block is proximal in the Purkinje system, because pacing in the His-bundle or left-bundle branch can significantly shorten QRSd.14 This good performance can be explained considering the two components of SSI, early systolic LV lateral wall stretch and mid-systolic septal rebound stretch: both are dependent septal-to-lateral wall contraction dyssynchrony, likely induced by an LBBB activation pattern, as well as preserved myocardial contractility.8 The latter likely takes into account the presence of scar, which is known to be associated with poor response, both in patients with ischaemic and non-ischaemic cardiomyopathy.15The superiority of SSI over other mechanical markers  to predict CRT response is in agreement with those reported by previous studies.et al.16 showed that presence of scar impairs EM coupling, even when scar is remote from late activated segments. Furthermore, Jadczyk et al.17 presented data confirming influence of EM coupling on kinetics and rotational pattern in patients with HF and LBBB. The poor performance of the TD–TPS relation in predicting CRT response may be explained by the limitations of TPS as mechanical marker, because in particular in the septum its measurement is complicated by multiple peaks.14 While poor TD–TPS relations in other studies might have been caused by difficulties in spatial or temporal alignment of the different measurements, in the present study all measurements were performed exactly at the same time and location. These unique in vivo data sets provided results that could be used as a reference for other studies based on conventional mapping systems and imaging techniques, such as strain ultrasound.While we hypothesized that the combination of electrical and mechanical measures would improve the association with CRT response, this turned out not to be true for the relation between time of depolarization and peak shorting (TD–TPS relation). In a previous study, Maffessanti et al.18 showed a similar additive predictive value for septal rebound stretch (the major component of SSI) and QRSarea, the area under the QRS complex in vectorcardiograms.On the other hand, combining electrical (TLVAT) and mechanical (SSI) variables improves the prediction of CRT response. While the excellent response in patients with small TLVAT and large SSI and the poor response in those with large TLVAT and small SSI were expected, it was worth noticing that reverse remodelling was comparable in the two intermediate categories, suggesting the need of a combined EM evaluation in the selection of CRT patients. Wouters 19Current measurements were performed using invasive measurements, but TLVAT and SSI may be assessed with less invasively. The recently introduced ultra-high frequency ECG provides a measure of conduction velocity underneath the precordial electrodes, called Vd, which may be indicative of TLVAT.Figure 1). Some investigators used single  wall imaging at a smaller angel to achieve a higher sampling rate.14Speckle tracking echocardiography is already well established. However, reliable SSI determination depends on proper timing of end systole, because especially septal strain may change considerably around this time  preserved/dispersed EM coupling and/or (ii) concordant/discordant latest electrical and mechanical activation regions. Furthermore, based on NOGA study results and coronary venous anatomy, a feasibility of optimal lead placement and pacing strategy could be simulated pre-procedurally supporting personalized clinical approach on conventional CRT vs. CSP.Albeit the present study focused on CRT, the characterization of the EM substrate could help identifying the patients most amenable to conduction system pacing (CSP), which is emerging as a valid method for delivering effective ventricular resynchronization.4 The study focused on the effects of EM substrate only, and did not consider other procedural correlates, such as lead positioning. Furthermore, we used a traditional definition of CRT response as ΔESV(%) ≥15%. Other studies employed other echocardiographic parameters (i.e. LV end-diastolic diameter),20 but ΔESV is the most commonly used index in large clinical trials corresponding with mortality and HF-related hospitalizations.21Study population of this study is relatively small compared with randomized trials on CRT. However, the novelty of the study relies on the approach adopted to derive EM measures based on mapping data, without the need of multimodality integration. Also, although scar burden was assessed from CMR, the current gold standard, this did not require spatial integration and could eventually be derived from mapping.Effectiveness of CRT significantly relies on the EM substrate and the scar burden. A combined EM approach was able to identify, despite similar ECG morphology, the opposite effects of TLVAT and TST on the reverse remodelling, the first associated with interventricular delay, the latter pointing to an adverse effect of slow intraventricular conduction on the left side.


We observed a significant increase in the incidence of new mitral regurgitation (MR) development , worsening with concomitant trastuzumab therapy , and a trend for tricuspid regurgitation development . ANT therapy is associated with the development of a new valvular disease, mainly MR, which may imply the need for a valvular focus in the monitoring of cancer patients.The association between anthracycline (ANT) and left ventricle (LV) dysfunction is well known; however, data regarding its direct effect on cardiac valve function is limited. We aimed to evaluate how ANT therapy affected valvular function in patients diagnosed with breast cancer. Data were prospectively collected as part of the Israel Cardio-Oncology Registry (ICOR). Patients underwent echocardiography exams at baseline (T1), during ANT therapy (T2), and after completion within 3 months (T3) and 6 months (T4). A total of 141 female patients were included, with a mean age of 51 ± 12 years. From T1 to T4, we observed a significant deterioration in LV ejection fraction (60.2 ± 1.5 to 59.2 ± 2.7%,  Advancements in early detection and cancer therapies have led to a significant improvement in disease-free years and overall survival for patients diagnosed with breast cancer . This exTo date, two-dimensional (2D) echocardiography has been used to monitor and diagnose cardiotoxicity during cancer therapy through changes in left ventricular ejection fraction (LVEF) ,6,7. WhiWhile the effect of ANT on LVEF and LVGLS is well known, data regarding the direct effect of ANT on cardiac valve function is limited . LongituThe aim of our study was to evaluate the direct effect of ANT therapy on valvular function in patients diagnosed with breast cancer.2, which is considered to be cardiotoxic [2 (T2), and following the completion of doxorubicin therapy within 3 months (T3) and 6 months (T4). Exclusion criteria included aged below 18, past ANT therapy, dexrazoxane (cardioxane) therapy, and baseline LVEF < 55%.This study was part of the Israel Cardio-Oncology Registry (ICOR) ,18,19,20diotoxic . AccordiA complete baseline medical history, cardiac risk factors, and medical treatment were noted in all patients from the electronic medical charts. Echocardiographic routine parameters, including LVEF, LVGLS, diastolic function, valvular function, and right ventricular (RV) function, were evaluated, as described in the echocardiography section. Cardiotoxicity was defined according to the ESC 2016 position paper  as canceHospitalizations and all-cause mortality were extracted from computerized patient charts and the Population Registry Bureau.Follow-up echocardiographic examinations were performed using the same strict protocol, personnel, and equipment  system, model Vivid S70). Overall, there were two technicians included in the study; however, the vast majority of the echocardiography tests were performed by the same single technician. All echocardiography exams were signed by the same single interpreting physician. Routine LV echocardiographic parameters included LV diameters and LVEF . LVEF waLVGLS was measured using EchoPac STE software and tracking within an approximately 5 mm-wide regions of interest (ROI). An end-systolic frame was used to initialize the LV boundaries, which were then automatically tracked throughout the cardiac cycle. Manual corrections were performed to optimize the boundary tracking as needed. Optimization of the images for endocardial visualization through the adjustment of gain, compress, and time-gain compensation controls was done prior to acquisition.p-value < 0.05 was considered significant for all analyses. All analyses were performed with the SPSS software .Continuous variables were presented as mean (±standard deviation) or as median (interquartile range) where appropriate, depending on the distribution. Categorical variables were described as absolute numbers and percentages. Linear mixed-effect models with repeated measures were used to evaluate the temporal trends between examinations for continuous echocardiographic parameters. For categorical variables, a linear-by-linear associations statistic (Mantel–Haenszel test) was used. Independent predictors for the deterioration of mitral incompetence  were determined in a multivariate binary logistic regression model including clinically relevant medical  and therapeutic  variables. A two-tailed From July 2016 to February 2021, 141 women diagnosed with breast cancer who received doxorubicin therapy were included, with a mean age of 51 ± 12 years. Baseline cardiac risk factors were relatively uncommon and cardiovascular disease history was rare, as displayed in 2). The potentially cardiotoxic agent trastuzumab  monoclonal antibody) was administered to 33 (23%) patients. Other concomitant anti-cancer therapy exposures, including cyclophosphamide, paclitaxel, carboplatin, and left breast radiation, were given to 100%, 92%, 9.2%, and 28% of patients, respectively.At T3, almost all patients (99%) had completed four cycles of doxorubicin therapy  and 47 (33–65) days following the first doxorubicin exposure, respectively. T3 and T4 exam results were acquired from 122 and 92 of the patients, respectively, with a median of 146 (130–208) and 245 (214–313) days following the initial doxorubicin exposure. Overall, T4 was performed at a median of 6.8 (5.7–9.0) months after the completion of the doxorubicin therapy.p = 0.0004) and LVGLS (−21.6 (−20.0–−23.0)% to −20.0 (−19.1–−21.1)%, p < 0.0001), as well as an increase in the LV end-systolic diameter (LVESD) (25 (22–27) mm to 27 (24–30) mm, p < 0.0001) (p = 0.002), of which only four patients presented with LVEF <53% (p < 0.0001)  . OverallVEF <53% . A simil 0.0001) . While sp = 0.02, and e’ septal, p = 0.0006), these changes mainly occurred in the time interval from T1 to T3, with a recovery or stabilization in T4. These changes did not result in a statistically significant trend in the composite classification of diastolic dysfunction grade (p = 0.23)  .p < 0.0001). Following exposure to ANT, an increasing correlative trend was seen in the portion of patients with moderate MR and above    . Further all MR) . In all  all MR) .p = 0.19, for TR of any severity). No cases of mitral or aortic stenosis were documented and no correlation was seen for aortic regurgitation (AR) (p = 0.57) (Similar trends were observed for tricuspid regurgitation (TR) valvular pathologies without reaching statistical significance  .p = 0.02) predicted new MR development independently, while age, hypertension, diabetes mellitus, hypercholesterolemia, smoking, paclitaxel therapy, left breast radiation, concomitant heart failure medications, or echocardiographic parameters at T1 did not (In a multivariate binary logistic regression model, only concomitant trastuzumab therapy (OR 5.99, 95%CI 1.35–26.6,  did not .During the follow-up, CTRCD was identified in four patients. Overall, two patients were admitted due to elevated troponin and chest pain, without LV dysfunction or coronary disease, and only one patient developed acute heart failure with reduced LVEF, which was considered to be tachycardia induced. Overall, three patients died during follow-up, from non-CV etiology.In the present study, we evaluated the incidence of new valvular dysfunction development among female patients diagnosed with breast cancer who were treated with ANT therapy. We observed a significant increase in the development of new MR, which was seen in the presence of normal LV function and regardless of exposure to left side radiation or trastuzumab therapy.The development of valvular heart disease in cancer patients has long been considered to be solely caused by fibrosis and calcifications that are secondary to radiotherapy . Only a The pathophysiology behind the development of MR following ANT is unclear. On one hand, it may develop as a secondary mechanism that is seen as a result of an overall reduction in LV function, which leads to LV dilation with structurally normal leaflets and chords . The exaSeparately, trastuzumab was independently seen to cause direct cardiotoxicity, resulting in a reduction in LVEF and the development of heart failure, with an increased incidence when given concurrently with ANT . Lange eLittle is known about the development of TR following ANT therapy. According to Lange et al. , the degAs the progression and development of cardiac dysfunction and heart failure in cancer patients are associated with increased mortality , the neeOur study had several limitations. First, it was a single-center study; however, its strength was the prospective nature following a homogenous population and the unity of all echocardiographs being performed by the same vendor, technician, and interpreting cardiologist. Second, we acknowledge that the relatively small number of patients reduced the statistical power of our results and larger trials are needed. Last, due to the short follow-up period and the low incidence of cardiac outcomes and mortality, the association of MR development to clinical outcomes was not evaluated. Long-term follow-up is needed to help assess MR development as an independent risk factor for LV dysfunction and cardiotoxicity.In conclusion, this novel study was one of the first to focus on the development of valvular heart disease related directly to ANT therapy in breast cancer patients. A significant increase in the development of MR was observed, thus suggesting a relationship to subclinical early changes in LV functionality and a need for closer valvular evaluation and monitoring throughout the continued follow-up of cancer patients.


This study assesses a possible cardiac dysfunction in individuals with Cornelia de Lange syndrome (CdLS) without diagnosed congenital heart disease (CHD) and its association with other factors. Twenty patients and 20 controls were included in the study divided into three age-dependent groups , and were evaluated using conventional echocardiography, tissue doppler imaging (TDI), two-dimensional speckle tracking and genetic and biochemical analyses. The left ventricular global longitudinal strain (GLS) was altered (< 15.9%) in 55% of patients, being pathological in the older group . The speckle tracking technique revealed a downward trend in the values of strain, strain rate and velocity, especially in the oldest group. Likewise, the ejection fraction (LVEF) and shortening fraction (LVFS) values, although preserved, also showed a decreased with age (p < 0.05). The analytical markers of cardiovascular risk and cardiac function showed no alterations. The molecular analyses revealed 16 individuals carrying pathogenic variants in NIPBL, two with variants in SMC1A, one with a variant in RAD21 and one with a HDAC8 variant. This is the first systematic approach that demonstrates that individuals with CdLS may present early cardiomyopathy, which can be detected by speckle tracking technique even before the appearance of clinical symptoms and the alteration of other echocardiographic or analytical parameters. For all these reasons, cardiological followup is suggested even in the absence of CHD, especially from adolescence onwards. Cornelia de Lange syndrome (CdLS)  is a congenital multisystemic-malformation syndrome with an estimated incidence of one per 10,000–30,000 live births [In the vast majority of patients, pathogenic variants occur de novo in genes encoding structural and regulatory components of the cohesin complex that, inter alia, are involved in the regulation of gene expression .NIPBL gene, which accounts for up to 70% of cases [SMC1A, SMC3, RAD21 [BRD4, HDAC8, ANKRD11 [MAU2 [The most frequently observed genetic cause of CdLS is a heterozygous pathogenic variant in the of cases , 4. Howe3, RAD21 , BRD4, H ANKRD11  and MAU211 [MAU2 , and cop11 [MAU2 . CurrentCdLS is characterized by typical facial features, growth failure, and limb abnormalities but also affects multiple organs and systems. In addition to the characteristic facial dysmorphism, growth retardation, intellectual disability, and gastroesophageal reflux, congenital heart disease (CHD) has been reported in a large number of CdLS patients . DespiteIn a previous study of cardiac function in patients with CdLS without CHD using conventional two-dimensional echocardiography, an age-related downward trend in left ventricular ejection fraction (LVEF) was observed. However, all values were in the normal range and all patients were asymptomatic . AlthougThe aim of this study was to evaluate cardiac function in patients with CdLS without CHD by using classical techniques, such as conventional echocardiography, the analysis of biochemical markers, and the two-dimensional speckle tracking technique, and assess its possible correlations with other factors in cases of myocardial dysfunction.NIPBL, SMC1A, SMC3, RAD21, HDAC8, ANKRD1, BRD4 and MAU2 genes. All patients, or their parents or guardians, signed a written consent form to participate in this study, which was approved by the Ethics Committee of Clinical Research from the Government of Aragón (Spain) .This case–control study included 20 individuals with CdLS  without CHD who were asymptomatic for cardiovascular disease and 20 healthy controls of the same age and sex. The sample was divided into three age groups . In addition, all individuals with CdLS were subjected to molecular analysis using WES or targeted NGS panels including the 2). We categorized CdLS phenotypes using the consensus criteria recently published in the first international consensus statement [Individuals with CdLS underwent anthropometric and physical examinations, and medical records were collected from their clinical histories. Weight was measured in kilograms (kg) using an AMGI-IMSA model, and height was measured in centimeters (cm) using the Harpenden model tallimeter. BMI was calculated by dividing weight (kg) by square height (mtatement . Classictatement . Heart rBlood samples were requested from CdLS patients (with the exception of four patients) to measure myocardial function biochemical markers (troponin-T and NT-ProBNP) and cardiovascular risk factors  by standard analysis procedures.American Society of Echocardiography and the European Association of Cardiovascular Imaging [A Siemens ACUSON SC2000 ultrasound system was used for cardiac evaluation. All measurements were carried out by two different researchers to decrease the interobserver variability. Two-dimensional ultrasound, color Doppler and tissue Doppler measurements were performed according to the recommendations of the  Imaging , 24.. The left ventricular ejection fraction (LVEF) was calculated using biplane Simpson’s method , left ventricular internal dimension at end-diastole (LVIDd), left ventricular internal dimension at end-systole (LVIDs), posterior wall at diastole (PWd), left ventricular mass in grams (LV mass) Fig. A, right hod Fig. B.Fig. 12Mitral inflow Doppler velocities and the peak early (E-wave) and late filling (A-wave) were measured by using pulsed-wave Doppler after placing the sample volume at the leaflets’ tips.Left ventricle tissue Doppler velocities, systolic velocity (s’), diastolic early (e’) and late (a’) lateral mitral annular velocities were calculated after placing the sample volume of the pulsed-wave Doppler at the lateral side of the mitral annulus Fig. C. Left vThe images were acquired using the same echocardiography equipment, and Velocity Vector Imaging 3.0 software was used to obtain left ventricular global longitudinal strain (GLS-LV) measurements. The cardiac cycle at end-diastole was selected on the echocardiogram, coinciding with the onset of the QRS complex. The four chamber planes of three cardiac cycles were acquired with a comprehensive adjustment of the image quality and a temporal resolution ≥ 60 frames/s Fig. A. In theGlobal longitudinal strain and strain rate values are expressed in absolute values. Reference values according to the different meta-analyses for global longitudinal strain vary between 15.9% and 22.1%, with a mean of 19.7% and a 95% confidence interval –30. We cData are presented as mean (standard deviation) values and percentages. The comparison between patients with CdLS and the control group was made using the Mann–Whitney or chi-square tests. A correlation study was performed by calculating Pearson’s correlation coefficient and scatter plots. A p value lower than 0.05 was considered statistically significant. Statistical analyses were performed using IBM SPSS Statistics® 20.0. software, and graphics were produced with GraphPad Prism 8 software.NIPBL gene, two carried a pathogenic variant in SMC1A, one carried a pathogenic variant in RAD21 and one carried a pathogenic variant in HDAC8 .The analytical markers of myocardial function (troponin-T and NT-ProBNP) and cardiovascular risk  were within the normal range in all cases.The echocardiographic values obtained after comparison of the control and study groups are shown in Table The diastolic function parameters are shown in Table When searching for correlations between the presence of this subclinical myocardial dysfunction and other factors , age was the only feature that seemed to correlate.It is worth noting that when the cohort of the study was divided into different age groups, a decrease in speckle tracking values was observed in all patient groups compared to appropriate controls. This was especially significant in the oldest group. The remaining values resulting from conventional echocardiography are shown in Table The lateral e’ wave values of the mitral annulus showed significantly lower values in individuals with CdLS over the age of 20. The speckle tracking technique also revealed a downward trend in the values of strain (GLS-LV), strain rate and velocity, resulting abnormal in most cases Fig. .Fig. 6EvCardiovascular defects represent a significant cause of morbidity and mortality in patients with CdLS. CHD has been described in one-third of the total individuals affected. The most frequent CHDs are septal defects (50%), pulmonary stenosis (27%) and coarctation of the aorta (9.6%). CHD contributes to approximately 25% of deaths during the first year of life . TherefoThere is limited information about the functional heart problems that may appear in these individuals, possibly because many of them did not reach adulthood in the past. However, a better knowledge of the molecular basis and, especially, the great advances that have been achieved in the clinical management of the syndrome have made it possible to extend their life expectancy. In the last few years, cases of heart failure and acquired cardiomyopathy have been described as responsible for 3% of deaths in patients with CdLS . In a prEchocardiographic methods based on the LVEF parameter as an indicator of systolic function offer volumetric measurements that provide guidance on cardiac function. However, the speckle tracking technique allows us to determine the degree of myocardial fiber deformation (strain) and obtain more accurate measurements of systolic function. This may significantly aid in the detection of early myocardial damage. Several studies have already used this technique in clinical practice to assess cardiomyopathy, and they observed that strain and SR values are sometimes decreased when LVEF and other echocardiographic parameters are not even altered –36.In the present study, the values obtained in individuals with CdLS with conventional echocardiography showed a downward trend in LVEF and LVFS, which correlated significantly with age. In addition, all values were within the normal range, suggesting that a cross-sectional echocardiographic analysis would not detect myocardial damage. In the same way, the TAPSE measurements, which correlate with the ejection fraction of the right ventricle, remained within the normal range. However, the mean values were lower compared to controls, especially in the oldest group. These data agree with those previously published .Although none of the individuals presented diastolic dysfunction , the mitIn this sense, numerous studies support the usefulness of speckle tracking echocardiography for the evaluation of early systolic dysfunction. In fact, our study shows abnormal strain values in more than half of the patients, and their downward trend correlated with age. This technique could substantially aid in the early detection of cardiomyopathy .In other genetic diseases, such as Duchenne muscular dystrophy, there is also a progressive decrease in strain values that allows early treatments. In individuals with Down syndrome, a decrease in strain values with preserved LVEF and increased left ventricular mass has been described , 23, butNIPBL and other genes of the cohesin complex alter heart development and produce structural defects, the underlying mechanisms of the development of cardiomyopathy in individuals without congenital malformations remain unknown. It has been proposed that patients with CdLS could undergo accelerated aging due to increased oxidative stress. This could prematurely deteriorate the heart, as it is an organ that is metabolically very active [Although there is evidence that pathogenic variants in y active , 40.NIPBL gene.Regarding phenotypic features, no differences were found their associations with the causal gene, although most of the patients in this study carried a pathogenic variant in the Analytical markers of cardiovascular risk  and myocardial function ) were within the normal range in all individuals studied. Although these biochemical parameters may be appropriate to identify cardiac dysfunction, they would not be useful for the early detection of these defects in patients with CdLS.It is worth noting that CdLS is a rare genetic condition, and few individuals reach adulthood due to the progression of the disease. This is a significant limitation in this work, as the available sample size is small.The results of this study suggest that patients with CdLS may develop subclinical cardiomyopathy, especially from the third decade of life onward. Taking this into account, it would be advisable to perform periodic cardiological evaluations that include the speckle tracking technique, despite having ruled out the existence of CHD in childhood.The implementation of this in clinical practice for better follow-up of patients with CdLS would allow early medical treatment that might delay the development of the clinical manifestation of myocardial dysfunction.