Introduction. Causes of acute heart failure in children range from simple myocarditis complicating chest infection to complex structural heart diseases. Objective. To describe patterns, predictors of mortality, and management outcomes of acute heart failure in children. Methods. In retrospective review, between February 2012 and October 2015 at a tertiary center, 106 admitted cases were selected consecutively from discharge records. Data were extracted from patients chart and analyzed using SPSS software package. t-test and statistical significance at P value < 0.05 with 95% CI were used. Result. Acute heart failure accounted for 2.9% of the total pediatric admissions. The age ranged from 2 months up to 14 years with mean age of 8 years. Male to female ratio is 1 : 2.1. Rheumatic heart disease accounted for 53.7%; pneumonia, anemia, infective endocarditis, and recurrence of acute rheumatic fever were the main precipitating causes. Death occurred in 19% of cases. Younger age at presentation, low hemoglobin concentration, and undernutrition were associated with death with P value of 0.00, 0.01, and 0.02, respectively. Conclusions and Recommendation. Pediatric heart failure in our settings is diagnosed mainly in older age groups and mostly precipitated due to preventable causes. Significant mortality is observed in relation to factors that can be preventable in children with underlying structural heart disease. Early suspicion and diagnosis of cases may reduce the observed high mortality. Heart failure is a clinical entity where the heart does not function to its level best as it does in its healthy state . Heart fObjective. The objective of this paper is to describe patterns, association for mortality, and management outcomes of acute heart failure in children. Method: it includes study design which was a hospital based retrospective review of admitted cases and setting which is Tikur Anbessa Specialized Hospital (TASH), a tertiary referral center in Ethiopia in the pediatric medicine. The hospital is located in the center of Addis Ababa the capital city; Department of Pediatrics has eight different service units to which these patient groups can be referred. The hospital has an average of 170 pediatric beds where 25–30 beds are occupied by pediatric cardiac admissions. Patients were coming from all corners of Ethiopia as the hospital is the biggest tertiary referral center.Sample. Patients' chart review was performed on 106 consecutive discharged patients with acute heart failure from February 2012 to October 2015. Patients under the age of 15 years from pediatric wards and emergency care unit with the discharge diagnosis of acute heart failure were included. Inclusion Criteria. The clinical criteria for heart failure in a pediatric patient were made if any three of the following were fulfilled: (1) significant tachycardia for age ; (2) significant tachypnoea for age ; (3) cardiomegaly ; (4) tender hepatomegaly of at least 3 cm size below the right costal margin [Independent variables included age, sex, duration of symptoms, underlying heart disease, precipitating cause, left ventricular systolic function (LV EF), right ventricular systolic function, date of start of treatment, type of treatment, and noncardiac treatment. Outcome variables included total pediatric admissions during study period, prevalence and etiology of heart failure, severity of heart failure, growth failure, pulmonary hypertension, recurrent chest infections (pneumonia), length of hospital stay, number of patients with improvement on discharge, mortality rate, and being defaulted.Cases with incomplete information and age above 14 years were excluded from the study. Sample size was determined based on the prevalence of heart failure in sub-Saharan African countries using a single population sample size calculation method. Questionnaires were developed based on desired information. Each query was appropriately pretested to determine appropriate information. Based on available data, information about the onset of illness, the presenting complaint, duration of illness, treatments received, and other pertinent clinical features were obtained. The type and severity of cardiac lesions were ascertained on the basis of physical examination and radiologic and electrocardiographic data, including echocardiography. The cardiac unit is equipped with 4 modern echocardiographic machines with pediatric probes, ECG machines, pulse oximeter devices.All cases were classified according to etiology, age, and clinical characteristics. Congenital and rheumatic heart diseases were defined according to the specific criteria available for their classifications , 12. DiaData were extracted from the patient charts and were filled into the questionnaire format by the investigators. Data quality was checked for its completeness, corrected on the spot for information that appeared inconsistent. To ensure consistency, double data entry was used. Data concerning number of pediatric visits, pediatric admissions, and cardiac cases during the study period were obtained from the record office.t-test was used to compare mean values. Statistical significance was considered when P value falls below 0.05 at 95% confidence interval. Results were presented in tables and figures.Data were entered into SPSS version 20, IBM, USA, and Excel 2013. Categorical data were presented as percentages or proportions. A chi-square test is used to determine whether an association between two categorical variables is significant or not. Continuous variables were analyzed using mean, median, and standard deviations. Student's Operational Definition. Congenital heart disease (CHD) is a problem with the heart structure and function that is present at birth. Rheumatic valvular heart disease (RVHD) is active or inactive disease of the heart that results from rheumatic fever and is characterized by reduced functional capacity caused by inflammatory changes in the myocardium or scarring of the valves. Mild anemia is defined as a hemoglobin concentration in the range of 9.5–11 gm/dL. Moderate anemia is defined as hemoglobin in the range of 8–9.5 gm/dL. Severe anemia is defined as hemoglobin concentration < 8 gm/dL [ 8 gm/dL . Treatme 8 gm/dL , 15. Pne 8 gm/dL , 16. Man 8 gm/dL , 18. TheDuring the study period, 3672 pediatric admissions were registered to the different pediatric units. Out of these, there were 106 cases of acute heart failure. The prevalence of acute heart failure was 2.9% of all pediatric admissions. The mean age at presentation was 8 years. All cases were classified in New York Heart Association (NYHA) or Rose functional class IV severity grade. Medication profile of cases is displayed in This hospital based retrospective chart review represented the general population of patients that sought care at Tikur Anbessa Hospital from all regions of Ethiopia. Data collection was reliable as the investigators coded all the diagnoses. The mean age at first presentation was low for mortality cases. This may have to do with the severity of underlying cardiac disease. Some of the findings were unique in our setting compared to reports from international sources. For example, infants and young children accounted for low proportion of the cases in this review. Massin et al. reported in one review that 58.1% of their study subjects were infants  In anothIn this review, female sex appears to be more commonly reported at all age groups. It appears from many studies that female sex has higher risk of developing cardiovascular disease compared to male sex . It has One of the prevailing findings in the current review is coexisting infections. Several studies reported respiratory infections to be common with acute heart failure particularly in children with structural heart disease , 25. TheChildren with rheumatic heart disease in Ethiopia are at risk of developing recurrence of rheumatic fever, as many of them are not receiving appropriate secondary prophylaxis with penicillin . It is rMalnutrition in heart failure has been ascribed to neurohormonal alterations, especially anabolic/catabolic imbalance and increased cytokine release. Anorexia becomes worse, particularly during acute decompensation of heart failure . HormonaThe number of cases who died in the current study is relatively higher compared to most reports in the sub-Saharan African countries and most others outside the region. We already discussed the role of malnutrition and anemia in increasing risk of death in heart failure. However, studies from other sub-Saharan African countries did not report the role of malnutrition in their reviews. In adult studies, the rate of malnutrition was not as high as seen in our current report. The high prevalence of undernutrition, anemia and coinfection in our context may explain the high mortality rate observed , 23.We observed in our study that captopril treatment was initiated with the lowest starting dose of 0.1 to 0.3 mg/kg/dose once (OD) daily up to three times daily (TID); however, escalation of dose was not subsequently done. Therefore, angiotensin converting enzyme inhibitor (ACE-inhibitor) therapy was, in general, suboptimal in our setting. However, literature recommends that, following a starting dose, a tittered dose as high as 0.5−2 mg/kg every 8 hours can be used in pediatric heart failure , 38. TheAge distribution of pediatric heart failure in our setting is dominated by older age population. Acute heart failure in infants and small children may have been underreported, due to misdiagnosis or early death of patients. Female sex predominance observed in adult reports is also noted in the current study. Underlying cardiac defects predisposing patients to heart failure were dominated by rheumatic heart disease in this review. This highlights the importance of national mobilization against this preventable condition. Undernutrition, anemia and infections were also important preventable comorbid conditions predisposing to death of cases.


Persistent left superior vena cava (LSVC) is a rare congenital venous anomaly that may be found at the time of cardiac device lead insertion.In this case series, we present clinical and long-term data of five patients with LSVC who underwent pacemaker (PM) or cardioverter defibrillator (ICD) implantation during the period of 10 years.Left-sided venous approach was used for device implantation in 3 patients with standard PM indications, whereas a right-sided venous approach and an epicardial approach had to be used in 2 patients who needed an ICD and biventricular PM, respectively. In post implantation period of 44 ± 29 months, one patient died due to stroke, one underwent heart transplantation, and 3 had atrial fibrillation.The long-term outcome of patients with persistent LSVC and implanted cardiac devices is mostly influenced by the presence of underlying heart disease. Persistent LSVC is a rare congenital venous anomaly  that canOur case series consists of patients with persistent LSVC who underwent pacemaker (PM) or ccardioverter-defibrillator (ICD) implantation between August 2000 and August 2010. The persistent LSVC was recognized during the device implantation when the guide wire entered the left subclavian vein but did not cross on the right side of vertebral column before entering the coronary sinus. Diagnosis of this anomaly was confirmed later by digital subtraction angiography (DSA)  or multiDuring a 10-year period, persistent LSVC was found in five (0.35%) out of 1390 patients undergoing first PM  or ICD (n = 94) implantation. Four patients had persistent LSVC and normal right superior vena cava (RSVC), whereas one patient (patient 2) had an absent RSVC. Clinical and long-term data of these patients are shown in In three patients with standard pacemaker indications, atrial and/or ventricular electrodes were successfully inserted via persistent LSVC and coronary sinus using a hand-shaped stylet and an active fixation lead. In the third patient, we could not achieve a stable position of defibrillation lead in the right ventricle during the shock delivery. Since the RSVC was present on MSCT , an ICD After cardiac device implantation, patients were followed-up for 44 ± 29 months. Among three patients with standard PM implantation, one with chronic AF died due to stroke despite of warfarin therapy, one had asymptomatic episodes of AF recorded by implanted PM, and one underwent PM replacement at 120 months of follow-up. A patient with implanted ICD developed paroxysmal AF and had several episodes of VT, successfully terminated by ICD therapy. Because of that, amiodarone was introduced for the treatment of both arrhythmias. A patient with dilated cardiomyopathy was not good responder to cardiac resynchronization therapy, and 18 months later, she underwent heart transplantation.Persistent LSVC occurs in 0.3% of individuals in the general population  and in 3The transvenous placement of cardiac device lead via persistent LSVC can be technically difficult, and in some cases, impossible , 11, 12.Regarding to clinical course, persistent LSVC is usually asymptomatic without additional congenital heart defects. Patients with a persistent LSVC may become symptomatic due to arrhythmias through fragmentation and stretching of the conduction tissue by dilated coronary sinus or ectopic pacemaker cells , 17. TheOur follow-up data show that the long-term outcome of patients with persistent LSVC and implanted cardiac devices is mostly influenced by the presence of underlying heart disease. Accordingly, a patient with hypertension and chronic AF died due to stroke, a patient with a prior myocardial infarction continued to have VT episodes, and a patient with chronic congestive heart failure underwent heart transplantation. These findings are consistent with the earlier reports, in which two patients with ischemic dilated cardiomyopathy underwent heart transplantation  and anotIn conclusion, persistent LSVC may severely complicate left-sided PM or ICD implantation and require alternative approaches for the lead insertion. The long-term outcome of patients with persistent LSVC and implanted cardiac devices is mostly influenced by the presence of underlying heart disease.


P<0.01). In addition, serum LOXL2 level was significantly correlated with the size of the left atrium (LAD) . Furthermore, the serum LOXL2 levels were significantly higher in AF patients with LAD ≥ 40 mm compared with those with LAD < 40 mm . And the Spearman’s correlation analysis further revealed that the mean bipolar left atrial voltage was inversely correlated with the LOXL2  in AF patients. Multivariate regression analysis further demonstrated that serum LOXL2  and LAD  were independent predictors of AF. In conclusion, serum LOXL2 levels were significantly elevated and were correlated with the degree of left atrial fibrosis in AF patients.Atrial fibrillation (AF) progression is generally accompanied by increased atrial fibrosis and atrial structural remodeling. Lysyl oxidase-like 2 (LOXL2) is known to play an important role in many fibrotic conditions, including cardiac fibrosis. The present study aimed to explore the relationship between serum LOXL2 levels and AF. Fifty-four AF patients and 32 control subjects were enrolled in the study. High-density three-dimensional electroanatomic mapping was performed, and mean bipolar voltage was assessed in AF patients. LOXL2 levels were measured by enzyme-linked immunosorbent assay. All patients underwent echocardiography to assess left atrium size and left ventricle function. Serum LOXL2 levels were significantly elevated in AF patients compared with the control group (526.81 ± 316.82 vs 240.94 ± 92.51 pg/ml,  Atrial fibrillation (AF) is a common cardiac rhythm disturbance and is associated with increased morbidity and mortality . AF occu2+ and lysine tyrosylquinone (LTQ)-dependent amine oxidases. LOXL2 was proposed to function similarly to LOX in the extracellular matrix by promoting crosslinking of collagen and elastin [Lysyl oxidase-like-2 (LOXL2) belongs to the lysyl oxidase (LOX) family, which comprises Cu elastin ,7. One r elastin . The preHowever, LOXL2 as a potential biomarker for cardiac remodeling in an AF cohort has never been investigated. We hypothesized that higher levels of LOXL2, reflecting more extensive structural left atrium remodeling, could predict the degree of atrial fibrosis in AF patients. Thus, the present study aimed to explore the association between LOXL2 and AF.Fifty-four paroxysmal or persistent AF consecutive patients with normal left ventricular function, who underwent a bipolar voltage map guided AF ablation between November, 2016 and April, 2017 were enrolled in the study. Thirty-two age- and gender-matched controls without AF who were hospitalized in our department were enrolled as the control patients. AF episodes either lasting >7 days or requiring termination by cardioversion, either with drugs or by direct-current cardioversion, were defined as persistent, whereas AF episodes self-terminating within 7 days were defined as paroxysmal. Exclusion criteria included noncardiac conditions with possible elevated LOXL2 levels such as liver cirrhosis, pulmonary fibrosis, autoimmune disease, and cancer. Patients with HF were also excluded from our study. Baseline demographic and clinical characteristics, including age, gender, complications, CHADS2 scores, and medication history, were recorded for all patients. N-terminal pro-B-type natriuretic peptide (NT-proBNP), serum creatinine (SCr), and alanine transaminase (ALT) were also recorded. Informed consent was obtained from each patient before enrollment. The study was in compliance with the principles outlined in the Declaration of Helsinki and approved by the Institutional Ethics Committee of Nanjing Medical University.After an overnight fast, blood samples were collected and immediately centrifuged and stored at −80°C until assayed. The frozen serum samples were rapidly thawed and brought to room temperature and assayed for the presence of human LOXL2 using enzyme-linked immunosorbent assay kits , according to the manufacturer’s instructions. Serial dilutions of known concentrations of human LOXL2 were used to construct a standard curve of the analytes. The serum levels of LOXL2 from the samples were estimated by extrapolation from a log–log linear regression curve determined from the serially diluted human recombinant LOXL2.All patients underwent transthoracic echocardiography to assess left atrium diameter and left ventricle (LV) function using standard views. The reported left atrial diameter (LAD) refers to left atrial anterior–posterior diameter, which was measured at end-systole on the M-mode image obtained from the parasternal long-axis view. The left ventricular function was assessed by the M-mode scanning of the left ventricular chamber, which was standardized by two-dimensional, short-axis views of the LV at the mid-papillary muscle level. The fractional shortening (FS) of the LV was defined as 100%, representing the relative change of left ventricular diameters during the cardiac cycle. The mean FS of the LV was determined by the average FS measurement of the left ventricular contraction over five beats.All AF patients underwent transesophageal echocardiography on the day of the study to exclude LA thrombus. Electrophysiological studies and ablations were carried out following the clinical routine in our center. In brief, a bipolar voltage map was carried out simultaneously with LA reconstruction, guided by the three-dimensional EnSite –NavX system .Intracardiac catheters were positioned as follows: (1) one decapolar coronary sinus (CS) catheter ; (2) His-bundle/right-ventricular catheter ; and (3) circular mapping catheter: a deflectable decapolar circular catheter  was advanced into the left atrium to create detailed LA and pulmonary vein (PV) geometries and acquire LA mapping points. The LA was accessed using two transseptal punctures.Intracardiac electrograms and 12-lead surface ECG were recorded using a digital electrophysiological recording system  and intracardiac electrograms were filtered at 30–500 Hz. The LA electroanatomic map was created during sinus rhythm. The electrogram from the proximal CS was used as the reference signal during the mapping procedure. To minimize the points which do not have good contact, the interior and exterior projection distances were set at 5 mm to the surface of LA geometry. Voltage maps for each patient were constructed during sinus rhythm. Local voltage was defined as the amplitude from the peak-positive to the peak-negative deflection of the local bipolar electrogram. The left atrium was divided into six regions as previously described elsewhere . The meat-tests, ANOVA, Fisher’s exact tests, or chi-square tests where appropriate. Univariate and multivariate binomial logistic regression analyses were performed to determine the independent predictors of AF. Spearman correlation analysis was performed to investigate factors related to the levels of LOXL2. A value of two-tailed P<0.05 was considered statistically significant. The statistical analysis was performed using SPSS software version 20.0 .In the present study, continuous variables are shown as the mean ± standard deviation, and categorical data are presented as frequencies. Comparisons among the baseline characteristics and levels of LOXL2 in different groups were performed by independent Student’s P<0.05), LAD , and NT-proBNP levels .Fifty-four AF patients with normal LV function and 34 age- and gender-matched control subjects were included in the study. Baseline demographic, clinical, laboratory, and echocardiographic parameters were compared between patients with AF and without AF and are presented in P<0.01) were significantly higher in patients with AF compared with the control group (P<0.01)  .r2 = 0.38, P<0.01)   in patie P<0.01) . Further P<0.01, .P<0.01, Figure 4r2 = −0.49, P<0.01)  were associated with AF. Multivariate regression analysis further demonstrated that serum LOXL2  and LAD  were independent predictors of AF in this patient group  1.011, 95% confidence interval (CI) 1.006–1.016, nt group .The present study reported the following results: (1) serum LOXL2 was significantly elevated in patients with AF compared with patients without AF. (2) LAD was independently correlated with serum LOXL2 levels in patients with AF. Serum LOXL2 levels were also significantly higher in AF patients with LAD ≥ 40 mm compared to those with LAD < 40 mm. 3) The level of serum LOXL2 was significantly correlated with the mean left atrial voltage in AF patients. Multivariate regression analysis further demonstrated that serum LOXL2 and LAD were independent predictors of AF. To our knowledge, the present study is the first to report the relationship between LOXL2 and the presence of AF. Since LOXL2 is an important fibrosis factor ,10, and  The leveThe lysyl oxidase family of proteins comprises LOX and four lysyl oxidase-like proteins . These proteins are copper- and quinone-dependent amine oxidases . LOX wasAF is a common cardiac rhythm disturbance and increases in prevalence with advancing age. The mechanisms causing and sustaining AF are multifactorial . Left atLAD is an important indicator of atrial structural remodeling in patients with AF. Previous studies have suggested that LAD size is positively correlated with atrial fibrosis . Our stuA large quantity of serum inflammatory and interstitial fibrotic related markers has been previously suggested as possible biomarkers for indication the AF risk or recurrence, in particular galectin-3 ,25–27. HIn addition, the relationship between brain-type natriuretic peptide (BNP) and LOXL2 was also analyzed in our study. BNP is a neurohormone generated by cardiomyocytes in the context of numerous triggers, most notably myocardial stretch . StudiesThere were some limitations to the study. First, the sample size is small; thus, large-scale studies are necessary to confirm our findings. Second, a follow-up study was not performed in this report. As an indicator for atrial fibrosis, it is reasonable to speculate that LOXL2 could be a candidate biomarker for guiding the recurrence of AF after cather ablation in clinic. Therefore, prospective studies should be conducted in the future to observe the effect of LOXL2 on the prognosis of patients with AF and to further explore the value of LOXL2 in assessing the success rate of AF ablation and the incidence of cardiovascular events.In conclusion, our study demonstrated that plasma LOXL2 was significantly elevated and also strongly correlated with the degree of left atrial fibrosis in AF patients with normal left ventricular function.


We hypothesised that, compared with culprit-only primary percutaneous coronary intervention (PCI), additional preventive PCI in selected patients with ST-elevation myocardial infarction with multivessel disease would not be associated with iatrogenic myocardial infarction, and would be associated with reductions in left ventricular (LV) volumes in the longer term.In the preventive angioplasty in myocardial infarction trial , cardiac magnetic resonance (CMR) was prespecified in two centres and performed  3  and 209  days after primary PCI.2, 69.3  vs 66.1 , p=0.48) and LV end-systolic volume  vs 30.7 , p=0.20). Non-culprit angiographic lesions had low-risk Syntax scores and 47% had non-complex characteristics.From 219 enrolled patients in two sites, 84% underwent CMR. 42 (50%) were randomised to culprit-artery-only PCI and 42 (50%) were randomised to preventive PCI. Follow-up CMR scans were available in 72 (86%) patients. There were two (4.8%) cases of procedure-related myocardial infarction in the preventive PCI group. The culprit-artery-only group had a higher proportion of anterior myocardial infarctions (MIs) (55% vs 24%). Infarct sizes (% LV mass) at baseline and follow-up were similar. At follow-up, there was no difference in LV ejection fraction , (culprit-artery-only PCI vs preventive PCI) 51.7  vs 54.4 , p=0.23), LV end-diastolic volume (mL/mCompared with culprit-only PCI, non-infarct-artery MI in the preventive PCI strategy was uncommon and LV volumes and ejection fraction were similar. Patients with acute ST-elevation myocardial infarction (STEMI) and multivessel coronary artery disease have an increased risk of adverse outcomes,8–10In the randomised trial of preventive angioplasty in myocardial infarction  ISRCTN70913605) trial,605 trialWe hypothesised that, compared with culprit-only primary PCI, additional preventive PCI in selected STEMI patients with multivessel disease would (1) not be associated with iatrogenic myocardial infarction secondary to the preventive PCI procedures and (2) would have a similar infarct size. CMR is the reference diagnostic imaging method for the assessment of infarct sizeThe PRAMI CMR substudy took place in the Golden Jubilee National Hospital, Clydebank and the Freeman Hospital, Newcastle. Both of these hospitals are regional cardiac centres. Acute STEMI management follows contemporary guidelines. Aspiration thrombectomy, direct stenting, antithrombotic drugs and other therapies were administered according to clinical judgement and in line with the guidelines.10.1136/heartjnl-2015-308660.supp1Supplementary dataCMR scans were performed during the index hospitalisation within  3  days post-randomisation and repeated 209  days after primary PCI.Information about MRI acquisition is provided in the online Image analysis was performed using a core laboratory with dedicated CMR software . CMR data were anonymised and then analysed in a random order by a CMR-trained cardiologist (KM) who was blinded to the treatment group assignment and all other clinical and health outcome data. Image quality was assessed using Likert scale quality scores.The myocardial mass of late gadolinium was quantified using computer-assisted planimetry as a hyperintense region over five SDs the signal intensity of remote  versus increased (thick/swollen) and oedema (yes/no) on T2-weighted sequences. This was done by two observers (KM and CB). T2-weighted CMR was not used to assess the area-at-risk as two sequences: a bright-blood T2-weighted ACUT2E method (acquisition for cardiac unified T2 oedema)The coronary angiograms underwent quantitative coronary analysis (QCA) of culprit and non-culprit lesions. The analyses were performed by an interventional cardiologist (BWH) who was blinded to the CMR and who had not been involved in any other aspect of the study. The QCA analyses were performed on a Centricity CA 1000 Cardiac Review 1.0 workstation .2) revealed by CMR at follow-up versus baseline. A prioritised secondary outcome was the occurrence of myocardial infarction in the territory of a non-culprit lesion treated by preventive PCI  .For a between-group treatment difference of 3.0 mL/m2 test, or a Fisher's exact test if any of the expected cell sizes were <5. Most continuous variables had a skewed distribution and are therefore presented as median and IQR, and analysed using Mann-Whitney statistical tests. Statistical analysis was not carried out on baseline characteristics as per the CONSORT statement recommendation.18Categorical variables were expressed as number and percentage of patients. Categorical variables were analysed using a χWe also carried out a multivariate regression analysis model, adjusting log-corrected total infarct size between groups for MI location (anterior vs non-anterior), time to reperfusion, age of participants at presentation, thrombolysis in myocardial infarction (TIMI) score (pre-PCI), Rentrop score (pre-PCI) and diabetes mellitus status.http://www.r-project.org) and Minitab 17 (http://www.minitab.com).A p value <0.05 was taken as significant. The statistical packages used in the analysis were R V.2.15  were enrolled in two hospitals in Glasgow and Newcastle. Of these, 84 (38%) participants   underwenThe participants were evenly distributed between the randomised groups (n=42 (50%) culprit-artery-only PCI; n=42 (50%) preventive PCI). The time from symptom onset to PCI was longer in the culprit-only group (average time 330±332 min) than in the preventive PCI group (273±248 min) but this difference was not statistically significant (p=0.38). Their clinical characteristics are described in The Syntax scores of the randomised participants were consistent with non-complex coronary disease . The SynPreventive PCI reduced the angiographic burden of disease and extent of myocardial jeopardy, as revealed by the post-PCI Syntax and APPROACH scores, respectively .At baseline, 80 (95%) of the cine imaging, and 73 (87%) of late gadolinium enhancement (LGE) imaging were of high quality. At follow-up, 68 (94%) of the cine imaging, and 68 (94%) of the LGE imaging were of high quality. At baseline 2 (2%) of the T2 weighted imaging and LGE were missing  had occurred in four participants assigned to preventive PCI and in seven participants assigned to culprit-artery-only PCI .2 and thus IV gadolinium contrast agent was not administered. One of the patients randomised to preventive PCI could not tolerate the CMR scan, so scanning was terminated after acquisition of the cine sequences.Infarct size and distribution revealed by late gadolinium enhancement imaging were similar in each of the randomised groups at baseline and at follow-up . Two patOn multivariate regression analysis, there was still no significant difference in infarct size between patients randomised to preventive PCI and culprit-artery-only PCI (p=0.74). Using the same model approach but with log-transformed infarct-artery infarct size instead of total infarct size, this model yielded a between-group p value of 0.95.On the baseline CMR scans, four patients randomised to preventive PCI had evidence of late gadolinium enhancement in the territory of a non-culprit-artery treated by PCI . In two The main findings in the PRAMI CMR substudy were that, in line with our first hypothesis, the incidence of iatrogenic myocardial infarction in the preventive PCI group was uncommon (4.8%), and appears to be lower than the incidence of non-infarct-artery MI (17%) in the population of patients who underwent CMR in the CvLPRIT trial.The strengths of our study include the use of multimodality CMR to assess infarct characteristics, including non-infarct-artery MI and LV remodelling.2), LV ejection fraction and infarct size. We used oedema imaging qualitatively to identify areas of acute injury, however, we did not quantify the area-at-risk and myocardial salvage index, as two different T2-weighted sequences were used during the course of the study .10There are two other clinical trials comparing culprit-only PCI to complete revascularisation in patients with STEMI and multi-vessel disease (MVD). The complete versus culprit-only revascularisation to treat multivessel disease after primary PCI for STEMI The PRAMI CMR substudy involved a limited proportion of the total number of participants in the main trial PRAMI trial, reflecting the fact that two of the six centres participated in the CMR study. Further studies are warranted. The distributions of some of the characteristics of participants in the substudy, for example, anterior infarct location, departs from those of the main trial population. The number of clinical events in the substudy is lower than in the main trial. Because of changes in the availability of oedema imaging methods, two T2-weighted CMR methods were used during the lifetime of the project, making quantitative assessment of area-at-risk and myocardial salvage not feasible. Two of the patients did not have late gadolinium CMR imaging (one in the culprit-only PCI group and one in the preventive PCI group). Measurement of cardiac biomarkers  was not part of the PRAMI trial protocol. There was heterogeneity in the duration of follow-up due to logistical reasons.We have performed an exploratory CMR substudy in the PRAMI participants. We conclude that the benefit from a preventive PCI strategy was unrelated to infarct size or LV remodelling, although the strength of this conclusion is tempered by the fact that study was underpowered to detect differences in these parameters. Further studies are required.Percutaneous coronary intervention (PCI) in patients with acute ST-elevation myocardial infarction (STEMI) and multivessel coronary disease is associated with improved clinical outcomes. However, doubt remains about the benefit of preventative PCI of other coronary arteries in addition to culprit vessel revascularisation.In this preventive angioplasty in myocardial infarction (PRAMI) cardiac magnetic resonance substudy, compared with culprit-only percutaneous coronary intervention (PCI), immediate preventive PCI of additional vessels was associated with a low incidence of iatrogenic myocardial infarction , 0 (0) vs 2 (5), p=0.15) with no difference at follow-up in left ventricular (LV) ejection fraction or LV volumes.A routine strategy of immediate preventive percutaneous coronary intervention is a reasonable approach in selected patients with acute ST-elevation myocardial infarction and multivessel coronary disease.


Right ventricular pacing often results in prolonged QRS duration (QRSd) as the resultof right ventricular stimulation, and atrial fibrillation (AF) may result. Theassociation of pacing-induced prolonged QRSd and AF in patients with permanentpacemakers is unknown.We selected 180 consecutive patients who underwent pacemaker implantation forcomplete/advanced atrioventricular block. All of the patients were paced from theright ventricular septum. Electrocardiography recordings were obtained at thebeginning and the end of pacemaker implantation. QRSd was measured in all 12 leads.The QRSd variation was calculated by subtracting the preimplantation QRSd from thepostimplantation QRSd.P = .022), and V6 differed significantly between theoccurrence and nonoccurrence groups. More QRSd variation in lead V6 and left atrial diameter were independent risk factors for AF occurrence. Receiveroperating characteristic curve suggested that QRSd variation in lead V6 could predictAF occurrence, especially for patients with long preimplantation QRSd.The occurrence of AF was observed in 64 (35.56%) patients (follow-up33.62 ± 21.47 mo). No significant differences inpreimplantation QRSd were observed between the AF occurrence and nonoccurrencegroups. The QRSd variation in leads V4 (54.22 ± 29.03 vs42.66 ± 33.79 ms,QRSd variation in lead V6 might be positively correlated with postimplantation AFoccurrence. In patients with pacemaker implantation, QRSd could be a complementarycriterion for optimizing the right ventricular septal pacing site, and smallest QRSdmight be worth pursuing. However, Hisian area pacing may be technically difficult and maynot be adequate in patients presenting with infra Hisian conduction problems. Considering the strong evidence of harmwith apical pacing, the septum and the RV outflow tract have been suggested asalternative pacing sites.One recent study has suggested that alternative RV pacing sites might be associated withthe risk of AF. Hisian area pacing compared with RV apex or RV septal pacing seems to beassociated with a lower risk of AF occurrence.Is there any way to reduce the risk of AF occurrence for pacemaker (PM) patients whocould neither minimize unnecessary RV pacing nor choice Hisian area pacing? Wehypothesized that there is a relationship between paced QRS duration (QRSd) andpostimplantation AF occurrence. In their study, QRSdwas the criterion for optimizing the RV pacing site. Mapping of the interventricularseptum was performed by means of custom shaped stylets until the smallest QRSd availablewas recorded. A complementary electrocardiography (ECG) criterion for optimizing the RVseptal pacing site might be necessary. And smaller QRSd might be associated with a lowerrisk of AF occurrence.One previous study has suggested that RV lead implantation guided by surface QRSd isfeasible.22.1We retrospectively analyzed 180 consecutive patients who underwent PM implantationfor complete/advanced atrioventricular block at the First Affiliated Hospital of SunYat-sen University from January 2010 to June 2016.The exclusion criteria were as follows: previous history of AF, implantablecardioverter defibrillator, or indication for cardiac resynchronization therapy,significant valve disease , heart surgery within the last 6 months before PM implantation, absence ofhigh percentage of ventricular pacing (≥40%) as observed at each follow-up,and poor-quality ECG.All patients were informed of the investigation and nature of the implantation, andwritten informed consent for implantation was obtained. And all experimentalprotocols complied with institutional ethical committees for Clinical Research andAnimal Trails of the First Affiliated Hospital of Sun Yat-Sen University and FDAguidelines.2.2Double-chamber PM systems were performed by a group of operators experienced in leadplacement. Prophylactic intravenous antibiotics were given half an hour before theprocedure. PM implantation procedure was done under local anesthesia. The RV lead wasinserted via the left- or right side subclavian venous approach. Once thetip of the RV lead made attachment with septal positioning, the screw was deployed.And posteroanterior and lateral chest x-rays were performed in all patientsundergoing pacing to corroborate the pacing site.All of patients were paced from the RV septum. Lead placement was performed using aconventional 7-French active-fixation lead in all patients. Lead positions wereconfirmed in the left anterior oblique and right anterior oblique fluoroscopic viewsduring implantation. No specific ECG criteria of final lead position were given. Thetarget RV septal pacing site was in the mid-upper third of the RV septum determinedby dividing the RV septum into thirds in the left anterior oblique >30 degreesfluoroscopic projection.2.3All the enrolled patients were followed for at least for 12 months. All patients werein sinus rhythm at the time of PM implantation. Before hospital discharge, clinicalevaluation and echocardiograms were performed. No data regardingAF episodes was collected during blanking period after device implantation. Themaximum tracking rate was individualized and the mode switch function was activated.Mode switch occurred, when the atrial rate exceeded 170 to 180 beats per minute for agiven number of beats or period of time according to the settings of the manufacturerof the PM. AF occurrence was defined as any episode of mode switch at least5 minutes in follow-up duration after the blanking period.,5Follow-up were performed at 1 and 3 months postimplantation and every 6 monthsthereafter. ECG was performed at each visit. Five weeks was defined as the blankingperiod.The follow-up was also conducted to determine the maximum percentage of ventricularpacing and the percentage of atrial pacing beats. High percentage of ventricularpacing was defined as ≥40%.2.4http://digitizer.source-forge.net). All ECG recordings were measured by 2 independentreaders who were blinded to this clinical research. We measured QRSd in 12 leads andexpressed the results in milliseconds. The preimplantation QRSd (QRSdpre)was measured from the earliest onset to the latest deflection of the QRScomplex. The paced QRSd(QRSdpaced) was measured from the beginning of the ventricular pacingspike to the end of the QRS complex. In each lead, the mean value for 3 consecutive complexes wasdefined as the final QRSd. Then we computed the average values (QRSdmean)of 12 leads. The QRSdmax was measured from the earliest onset in any leadto the latest deflection in any lead. The QRSd variation was measured by subtracting theQRSdpre from the QRSdpaced(QRSdpaced – QRSdpre).Standard 12-lead ECG measurements were recorded at the beginning and the end of thedevice implantation. Then ECGs were digitized and measured using Engauge Digitizer5.1 software  and Stata12 . Continuous variables were presented asmeans ± standard deviation. Abnormally distributed data wereexpressed as medians (upper and lower quartiles). Between-group comparisons ofnormally distributed data were performed using independent-sample paced in lead V4, QRSdpaced in lead V6, percentage ofatrial and RV pacing, left atrial diameter, left ventricular ejection fraction, age,QRSdmean-pre , left ventricular end-diastolic diameter, diabetes,hypertension, coronary artery disease, use of angiotensin I-converting enzymeinhibitory or angiotensin II receptor blocker, use of beta-blockers, and use ofcalcium antagonists. The Cox proportional hazards model depends on the assumption ofa constant hazard over time, which was evaluated by a global goodness of fit testproposed by Schoenfeld.,11Cox's proportional hazard model was used to estimate hazard ratio ofoccurrence of AF for QRSd variation in lead V6 adjusted for various potentialconfounders selected by forward stepwise regression method between: QRSd variationand QRSdP < .05.A receiver operating characteristic (ROC) curve was constructed to evaluate thesensitivity and specificity of various cut-off values of QRSd indices for predictingpostimplantation AF occurrence. Statistical significance was denoted at33.1A total of 185 adult consecutive patients underwent permanent RV septal pacing forcomplete/advanced atrioventricular block (between January 2010 and June 2016). Fivepatients were excluded from our study for dislodgement of the RV lead, which wasmanaged by replacing the lead close to the original site (RV septum).2 value. The clinical characteristics of all patients, andthe AF occurrence and nonoccurrence groups are presented in Table P = .009).The study cohort was composed of 180 patients. Seven patients were infected after PMimplantation and all of them received antibiotics. Among them, 1 patient becamechronically infected. During a mean follow-up of 33.62 + 21.47months, AF occurred in 64 patients (35.56%). Among patients with AF occurrencepostimplantation, 22 were prescribed anticoagulant  according to CHADS3.2P < .001). A comparison of QRSd databetween the occurrence and nonoccurrence groups indicated that QRSdpre didnot differed in any of the 12 leads between the 2 groups , and V6 between the 2 groups (Table P = .022), and V6 differed significantly between the2 groups   were introduced in the Cox proportional hazard model and left atrial diameter independently predicted postimplantation AF occurrence. Inorder to approve the proportional hazards assumption, a global goodness of fit testproposed by Schoenfeld was done.,11 According to this test,proportionality assumption was confirmed for all covariates and whole model(P = .990).Consequently, these 4 parameters  represented the valueof hazard ratio which caused by every 1 unit increment of variable quantityXj, when other covariant quantitiesremained unchanged. So HR of QRSd variation in lead V6 was caused by every increaseof 1 number in millisecond. According to medical knowledge, interval scale of QRSdwas defined as 40 ms (k = 40). Thenwe calculated HR’ via following calculation formula:Among this calculation formula,expand short QRSdmean-pre . Independent-sample t tests and Cox model wereperformed again (Tables All of patients were divided into 2 subgroups according to longQRSdmean-pre (<120 ms), the QRSdvariation in leads V6  differed significantly between the2 groups. And Cox model concluded that a longer QRSd variation in lead V6 independently predictedAF occurrence. When interval scale of QRSd was defined as 40 ms, HR’was 1.963 (95% CI 1.221–3.391).In subgroup of short QRSdmean-pre (≥120 ms), the QRSdvariation in leads V5 , and V6 differed significantly between the2 groups. And Cox model concluded that a longer QRSd variation in lead V6 independently predictedAF occurrence. When interval scale of QRSd was defined as 40 ms, HR’was 5.387 (95% CI 1.270–22.544).In subgroup of long QRSd3.4mean-pre (<120 ms), the area underthe curve for the QRSd variation was 0.616 (95% CI 0.525–0.708). A QRSdvariation ≥68.2 ms in lead V6 exhibited the best combined sensitivityand specificity for AF occurrence . In subgroup oflong QRSdmean-pre (≥120 ms), the area under the curve was0.826 (95% CI 0.685–0.967). A QRSd variation ≥11.8 ms exhibitedthe best combined sensitivity and specificity for AF occurrence .ROC curve analysis was performed to evaluate the ability of the QRSd variation inleads V6 to predict AF occurrence Fig. . Insubg4,13And QRSd was correlated with AF occurrence in patients with heart failure. However, there is no published data onthe association of AF occurrence and paced QRSd in patients with PM. Our study suggestedthat the QRSd variation in lead V6 was positively correlated with postimplantation AFoccurrence, and QRSd could be a complementary criterion for optimizing the RV septalpacing site.Previous studies have demonstrated that the cumulative percentage of RV pacing andalternative RV pacing sites might be related to the risk of AF occurrence.4.1,16 And in some studies, low part of RV septum was classified as RVapical portion. The conflictingdata regarding RV septal and RV apical pacing might be contributed to themultiplicity of possible lead positions in RV septum despite careful positioning inthe fluoroscopy projection. For example, Shimony et al concluded that left ventricular function was worsewith RV apical than with RV nonapical pacing. By contrast, Ng et al concluded that RV apical pacinggroup had better left ventricular function than RV septal pacing group. In addition,although Pastore et al concluded that the site of RV pacing might affect the risk ofAF, no statistically significant difference in the risk was observed between RVapical and RV septal groups. And Pastore et al suggested that it might be due to a high degree ofheterogeneity in RV septal pacing sites.The RV septum is a relatively large area and fluoroscopy could not take into accountthe various anatomic variations of the region. RV septal pacing consist of aheterogenous group of pacing sites, ranging from the RV free wall to the midseptalsegment and even in the free wall of the true outflow tract. In addition, the RVseptum can be paced from high, low, and midseptal positions.paced. This question shouldbe discussed further in a large prospective study.It is not clear that whether these different RV septal locations yield differenteffects to AF occurrence by variation of QRSd4.2 suggested thatthere was a correlation between shortened QRS complex duration and improvement ofleft ventricular ejection fraction in PM patients. Sakatani et al suggested that shorter QRSd wasassociated with better prognosis in patients with PM. And our results suggested thatthe QRSd variation in lead V6 could predict AF occurrence in patients with PM,especially for patients with long QRSdmean-pre(≥120 ms).Malecka et al,20 These results raise the possibility that, in thefuture, we might need to optimize the RV septal pacing site based on conventionalx-ray and complementary ECG (QRSdpaced) in individual patients. Schwaab etal suggested that RV lead implantation guided by surface QRSd was feasible. Mappingof the interventricular septum was performed by means of custom-shaped stylets untilthe smallest QRSd available was recorded. And our results of ROC curve suggested that during RV septallead placement, variation of QRSd in lead V6 should be <11.8 ms inpatients with long QRSdmean-pre and be <68.2 ms in patientswithout.Given that there was no specific ECG criteria of final lead position in RV septum inprevious studies.4.3 Long QRSd obtained by artificial stimulation is completelydifferent with long QRSd on the patients with heart failure. In patients with PM, thepathways of left ventricular activation are different from normal. It is supposedthat the more myocardium activated by muscle conduction before the ectopic activationfront enters the specialized conduction system, the longer the QRSd.QRSd represents the electrical activation of both the left and right ventricles.Although the relationship between QRSd and AF in patients with heart failure hasalready been clearly identified. Previous studies suggested that shortened QRSd was related tohomogenization of left ventricular contraction and improvement of systolic functionin patients with PM.,18 Second, QRSd was correlated withinterventricular dyssynchrony in patients with PM. And ventricular dyssynchrony could facilitate theonset of AF.The pathogenesis of QRSd variation and its association for AF occurrence afterimplantation remains unclear. The underlying mechanism may involve ventriculardysfunction and dyssynchrony. First, with long period of ventricular pacing, theunderlying ventricular dysfunction contributes to left atrial remodeling/stiffnessfurther decreasing the left atrial function. Then reduced left atrial reservoirfunction estimated by the total left atrial emptying fraction markedly increases thepropensity for first AF or atrial flutter.4.4Third, lead V6 is the furthest precordial ECG leads from the RV septal leadplacement. As a result, any QRSd change induced via PM may be magnified in leadV6.Our results revealed that only lead V6 QRSd was associated with postimplantation AFoccurrence. First, precordial leads  could record theelectrical activity of the myocardial wall directly below the exploring electrode,whereas peripheral leads  could not explore specificsegments of the myocardium but the whole electrical activity of the heart. Second,right precordial leads , exploring thinner myocardial areas, has a shorterduration than that of the left precordial leads . For example, intrinsicoiddeflection in leads V1 and V2 is <35 ms, whereas in V5 and V6 it is<45 ms.4.5mean-pre (≥120 ms) reflects various ventricularconditions, such as conduction disturbance, ventricular fibrosis, and mechanical leftventricular dyssynchrony. Andthese conditions could facilitate the onset of AF. By contrast, Pastore et al suggested that the presence of bundlebranch block was associated with a lower risk of AF in patients with PM.Long QRSdmean-pre(≥120 ms) had nothing to do with AF occurrence. And our subgroupanalysis suggested that, with or without the presence of long QRSdmean-pre(≥120 ms), a longer QRSd variation in lead V6 independently predictedpostimplantation AF occurrence.However, our Cox model suggested that the presence of long QRSd5mean-pre (<120 ms), area under the curve was justonly 0.616. This might be contributed to several confounding factors that wouldinevitably contribute to AF occurrence, such as percentage of RV pacing, percentage ofatrial pacing, left atrial diameter, left ventricular ejection fraction, age, and soon.,13 Furthermore, to improve the reliability of our conclusion, thesefactors were introduced in our logistic analysis. However, the difficulty in makingadequate adjustment for the different populations strongly suggests that the analysis ofthe data should be confirmed in a large, multicenter prospective study. Moreover,because of the small sample size in subgroup of long QRSdmean-pre(n = 31), greater caution should be applied to the results ofthis subgroup.There were several limitations in this study. This study featured a retrospective designand was conducted at a single center with highly selected patients. For subgroup ofshort QRSd6An increase in QRSd post-implantation compared to preimplantation in lead V6 might bepositively correlated with postimplantation AF occurrence. In patients with PMimplantation, QRSd could be a complementary criterion for optimizing the RV septalpacing site. Considering this was a retrospective study, a large, multicenterprospective cohort study might be necessary to confirm the association between QRSdvariation and postimplantation AF occurrence.


Cardiovascular disease (CVD) is a risk factor for cognitive impairment in the elderly. Manifestations of subclinical CVDs can be found in patients with cognitive impairment. The aim of the present study was to test the hypothesis that patients with mild cognitive impairment (MCI) have different magnetic resonance imaging (MRI)-derived regional myocardial motion indices compared with healthy controls.Eleven MCI patients  and 11 sex−/age-matched healthy volunteers were enrolled. All of the participants underwent a head MRI and cardiac MRI. Global cortical atrophy (GCA) was graded on the head MRI. The left ventricular ejection fraction (LVEF) and regional strain, strain rate, displacement and velocity were measured on cine images. The GCA scores, global cardiac function and regional myocardial motion indices were compared between MCI patients and healthy controls using the t-test.p = 0.048). However, there was no significant difference in LVEF between MCI patients and controls. Compared to healthy controls, MCI patients had a lower peak radial strain , lower peak diastolic radial strain rate , lower peak diastolic circumferential strain rate , lower peak systolic radial displacement , lower peak diastolic radial velocity , and lower peak diastolic circumferential velocity .MCI patients had a higher GCA score than healthy controls .The online version of this article (10.1186/s12872-018-0824-2) contains supplementary material, which is available to authorized users. These outcomes suggest that advancements in cardiovascular treatment strategies could successfully extend the lives of CVD patients but did not directly improve AD outcomes. By the time CVD is detected and treated, its impact on the brain might have already been irreversible, suggesting that early intervention for subclinical CVD is critical to prevent AD [. Unfortunately, conventional quantitative cardiovascular indices of global cardiac function, such as left ventricular ejection fraction (LVEF), are insufficient to link subclinical CVD to AD [that myocardial ischemia and dysfunction in the early stage of CVD can occur at a regional level and might not initially impact the global cardiac function. Therefore, cardiac imaging biomarkers that can better bridge subclinical CVD to AD are highly desired.Alzheimer’s disease (AD) is the most common cause of cognitive impairments, including mild cognitive impairment (MCI) and dementia, in older adults . CardiovRecently, quantitative biomechanical indices acquired using magnetic resonance imaging (MRI), such as strain, strain rate, displacement and velocity, have been adopted to comprehensively describe abnormal myocardial motion patterns . CompareThis prospective study was approved by the local ethics review board and written informed consent was obtained from all of the participants. From 2012 to 2017, the medical records of MCI patients in our institution were reviewed. All of the MCI patients were clinically diagnosed at our institution by experienced neurologists according to the guideline published by National Institute on Aging-Alzheimer’s Association workgroups in 2011 . SpecifiAll of the participants were imaged with a 3.0 T clinical MRI scanner  by two certified MRI technicians. The cardiac MRI and head MRI were consequently performed on the same day with a 4-element phased-array surface coil and a head coil, respectively. Blood pressure (BP), body weight and height were measured for each participant immediately before MRI scans. Related health information for assessing traditional cardiovascular risks was collected by checking the medical history.After localization of the heart, cine images were acquired by using a Fast Imaging Employing Steady-state Acquisition (FIESTA) sequence at two-chamber, three-chamber and short-axis views. The short-axis cine images covered the heart from base to apex with 10–12 slices. The imaging parameter included: TR/TE = 3.6/1.6 ms, field of view (FOV) = 380 × 380 mm, matrix = 512 × 512, slice thickness = 8 mm. Twenty retrospective phases were constructed within a cardiac cycle.2, matrix = 512 × 512, slice thickness = 8 mm. T2WI: TR/TE = 3500/100 ms, FOV = 200 × 200 mm2, matrix = 512 × 512, slice thickness = 8 mm.A three-plane localizer was used to prepare the imaging planes. A fast spin echo (FSE) sequence was run on axial and sagittal views to obtain T1 weighted images (T1WI) and T2 weighted images (T2WI) covering the whole brain. The imaging parameters included: T1WI: TR/TE = 750/25 ms, FOV = 200 × 200 mmAll of the images underwent regularly checks by reviewer #1  before cardiac MRI analysis was started. Global cortical atrophy  scores were then graded semi-quantitatively by reviewer #1 based on T1WI and T2WI images using criteria from the existing literature . Grades All of the cardiac images were analyzed using Circle CVI42 software  on a dedicated workstation . After short-axial and four-chamber cine images were loaded, reviewer #1 manually traced the endocardial and epicardial borders of the left ventricle (LV) to define region of interest (ROI) at the end-systolic and end-diastolic phases, respectively. MRI-derived global cardiac function and regional myocardial motion indices, such as LVEF, strain, strain rate, displacement and velocity, were automatically calculated based on the ROIs. Regional motion indices in the radial and circumferential directions were mapped on an AHA 16-segment LV model. Long-axis motion indices were mapped on a 6-segment LV model. Measures for each participant were output as a single Microsoft Excel spreadsheet for further analysis.Reviewer #1 re-analyzed the data of all of the cases after a one-month interval to test the intra-observer agreement in measurements of regional myocardial motion indices. Reviewer #2  independently analyzed all of the cases with the same workflow to test inter-observer agreement of GCA grading and myocardial motion measurements.p value < 0.05 was considered to demonstrate statistical significance.Data are presented as the mean ± one standard deviation (SD). GCA scores, LVEF, and regional myocardial motion indices (16 data points on short-axis views and 6 data points on four-chamber views) were compared between two participant groups using the t-test. Pearson’s correlation coefficient (r) was applied to test correlations between GCA scores and cardiac motions indices. Bland-Altman plots were used to present intra- and inter-observer variations for measuring regional myocardial motion indices. Inter-observer agreement of GCA grading between two reviewers were evaluated using intra-class correlation coefficient (ICC). Statistical analysis was performed using SPSS software . A p = 0.048). However, there were no significant differences in LVEF between MCI patients and controls . Figure All 22 participants underwent cardiac and head MRI successfully. The image quality of all the participants was eligible for quantitative study. No significant differences in cardiovascular risks were found between the two participant groups Table . Head MRp < 0.001), lower peak diastolic radial strain rate , lower peak diastolic circumferential strain rate , lower peak systolic radial displacement , lower peak diastolic radial velocity , and lower peak diastolic circumferential velocity . See Fig. Compared to healthy controls, MCI patients had a lower peak radial strain . Bland-Altman plots showed small intra- and inter-observer variations in measuring peak strain at the radial, circumferential and long-axis directions; see Additional file In the present study, we quantitatively described MRI-derived regional myocardial motion patterns from multiple aspects in MCI patients. Compared to sex- and age-matched healthy controls, MCI patients had lower peak regional myocardial strain, strain rate, and velocity in certain directions or time phases. These findings suggest that regional myocardial motion indices, as early indicators of cardiovascular health, are associated with cognitive decline.p = 0.02), brain volume (p = 0.03) and lateral ventricular volume (p = 0.048) [Different interpretations of these conflicting results generated discussion regarding whether “a healthy heart will result in a better brain”. Hence, there is no conclusive evidence on whether preventing or treating CVDs benefits AD management.Although cognitive decline can be the result of various brain disorders, including tumors, strokes, trauma, infections, neurotoxicity and inherited genetic factors, AD accounts for 60 to 80% cognitive impairments in older adults . Almost = 0.048) . However= 0.048) . McGuinn= 0.048) . DiffereRecent studies have shown that CVDs might have a long-standing effect on the brain and therefore recommended early cardiovascular treatment/prevention to benefit the brain [. However, current cardiovascular indices presenting global cardiac function, are insufficient for determining AD risk. Therefore, accurate description of regional myocardial motion patterns has high potential to provide critical information for assessing subclinical CVDs and their potential effects on the development of AD. Impaired regional myocardial motion patterns can be observed without a decrease in LVEF in asymptomatic subjects with prominent cardiovascular risk conditions [In the present study, we further demonstrated that regional myocardial motions indices from the LV were different between MCI patients and healthy controls while there was no significant difference in LVEF. More interestingly, differences in motion indices accompanied divergences in GCA scores in the two participant groups despite there being no direct linear correlations between them. The connections among cardiac MRI, GCA scores and MCI suggest inherent correlations between the existence of subclinical CVDs and neurodegenerative changes. Although further investigations are needed to determine the mechanisms underlying our observations, these cardiac imaging biomarkers have the potential to inform the development of a cost-efficient prevention/treatment strategy simultaneously targeting CVD and AD, the two prominent threats to aging populations.he brain . Howevernditions –22. Kresnditions . In the The present pilot study had limitations. First, we had a small sample size due to strict enrollment criteria for MCI patients. Therefore, we could only balance prominent cardiovascular risks, such as diabetes mellitus (DM), HTN, and body mass index (BMI), in data analysis. For the same reason, we were unable to distinguish subtypes of MCI (amnestic and nonamnestic) in the present study. Second, according to current cardiac MRI techniques, which might require frequent breath holding during image acquisition, it was difficult to perform cardiac MRI on patients with dementia. As a result, we had to intensively exclude dementia patients. Third, we were unable to acquire regional myocardial motion patterns from the right ventricle (RV) because the thin wall of RV substantially affects the contour drawing and therefore affect the accuracy of motion measurements. Fourth, the aim of the present study was to evaluate the clinical value of regional myocardial motion indices. Therefore, we only ran regular T1WI and T2WI on the participants to obtain GCA despite there being other MRI methods that can represent brain health from other aspects. Fifth, we were unable to determine a causal correlation between changes of regional myocardial motion and cognitive decline. A large-scale, longitudinal study has been designed to further assess the clinical value of cardiovascular imaging biomarkers in the management of AD.MRI-derived regional myocardial strain, strain rate and velocity were found to be different between MCI patients and healthy controls. Regional myocardial motion indices have the potential to become novel quantitative imaging biomarkers for representing the risk of neurodegenerative disorders, such as AD.Additional file 1:Contain Bland-Altman plots for variations in measured regional myocardial motion indices. (DOCX 349 kb)


Fabry disease is a rare X-linked disorder characterized by deficiency ofα-galactosidase A, leading to progressive accumulation of glycosphingolipid in various organs, including the heart. Several studies have pointed out the unique pre-contrast T1 value character of classic Fabry cardiomyopathy, which is lower than the normal myocardium. In Taiwan, several recent studies pointed out a surprisingly high incidence of a later onset Fabry mutation (IVS4+919G>A). There is a lack of information about the T1 value of this Fabry variant cardiomyopathy in the literature. We aim to present the T1 value of this subtype of Fabry disease on cardiac MR.As referred from pediatric cardiologist, we collected cases with Fabry mutation (IVS4+919G>A), proved via gene analysis from blood sampling and endomyocardial biopsy. They underwent MR study from March 2015 to July 2015. We recorded the location of delayed myocardial enhancement according to AHA 16-segment model and measured the thickest segment of left ventricular (LV) in short axis view at end diastole. We used conventional look-locker sequence (pre- and post contrast) and the Circle CVi42 software to calculate T1 value of target myocardium. Another 16 normal volunteers (with age and gender matched) were collected and they underwent non-contrast cardiac MR with T1 map evaluation. The myocardial pre-contrast T1 values were compared by t test as follows: Fabry cases vs. control group, Fabry cases with left ventricular hypertrophy  vs. Fabry cases without LVH. The pre-contrast T1 values are compared by paired t test as follows: whole LV myocardium vs. interventricular setum vs. LV inferio-lateral wall, enhanced myocardium vs. non-enhanced myocardium.2. The T1 value of LV myocardium was significantly lower in Fabry variant cases than the normal control . No significant difference of T1 value of LV myocardium was noted between Fabry variant cases with and without LVH . The T1 value of whole LV myocardium and inferiolateral wall of fabry cases were both higher than that of interventricular septum of fabry cases . In fabry cases with delayed enhancement of LV, The enhancing myocardium demonstrated higher T1 value than non-enhancing myocardium .A total of 16 patients  were enrolled in this study and the basic characters of LV were as follows: ejection fraction of LV=64.0 ± 10.5%, LV stroke volum=103.2 ± 28.3 ml, LV mass=167.4 ± 68.3 gm, LV mass index=94.5 ± 37.8 gm/mIn our study, Fabry variant cases demonstrated lower pre-contrast T1 value of LV myocardium comparing with normal control cases. No significant difference of pre-contrast T1 value was noted between fabry variant cases with and without LVH.


We aimed to quantify atrial and ventricular myocardial deformation in Ebstein's Anomaly (EA) in a case-control study with cardiovascular magnetic resonance (CMR) feature tracking and to correlate changes in cardiac performance with the severity of disease and clinical heart failure parameters.Atrial and ventricular deformation was measured using CMR feature tracking in 30 EA and 20 healthy control subjects. Atrial performance was characterized using longitudinal strain and strain rate parameters for reservoir function, conduit function and booster pump function. Ventricular performance was characterized using RV and LV global longitudinal strain (εl) and LV circumferential and radial strain (εc and εr). Volumetric measurements for the ventricles including the Total Right/Left-Volume-Index (R/L-Volume-Index) and heart failure markers  were also quantified.EA patients showed significantly impaired right atrial performance, which correlated with heart failure markers . LA function in EA patients was also impaired with atrial contractile function correlating with NYHA class. EA patients exhibited impaired RV myocardial deformation, also with a significant correlation with heart failure markers.CMR feature tracking can be used to quantify ventricular and atrial function in a complex cardiac malformation such as EA. EA is characterized by impaired quantitative right heart atrio-ventricular deformation, which is associated with heart failure severity. While LV function remains preserved, there is also significant impairment of LA function. These quantitative performance parameters may represent early markers of cardiac deterioration of potential value in the clinical management of EA. •CMR feature tracking can be performed in complex congenital heart disease as Ebstein's Anomaly.•Ebstein's Anomaly is associated with impaired right atrial and right ventricular strain markers.•LA function as expressed by strain markers from CMR is also impaired.•Atrio-ventricular deformation markers may be helpful in the management of Ebstein's Anomaly. Many EA patients suffer from progressive right heart failure and impaired physical exercise capacity at some stage in their life The clinical relevance of impaired atrial function in heart failure development is increasingly recognized Alterations in atrial function – which reflect changes in myocardial deformation itself but are also dependent on RV function, loading conditions and tricuspid regurgitation – may possibly represent early markers for deterioration of overall cardiac function, but have not been defined in EA 22.1From a total of fifty-eight patients with EA in the database of the Department of Pediatric and Adult CHD, University Medical Center Göttingen, Germany, 31 patients with EA were prospectively recruited in this case-control study and gave written informed consent to participate. Exclusion criteria included age < 10 years, implantable electronic cardiac devices, associated complex cardiac malformations and claustrophobia. The 31 patients  were examined prospectively within one day between January 2013 and July 2013 and compared to 20 healthy matched controls . Six of the EA patients had undergone previous cardiac surgery . Seven of eight patients with atrial septum defect (ASD) had undergone ASD closure . Sinus rhythm was documented during the examination and no higher degree AV blocks were noted. The study protocol included medical history, New York Heart Association (NYHA) classification, clinical examination, brain natriuretic peptide (BNP) and CMR. The study protocol complied with the Declaration of Helsinki and was approved by the local clinical ethics committee.2.2CMR was performed according to current guidelines 2.3Myocardial FT was performed using dedicated software . Results are based on averaging of three repeated measurements by the same observer to maximize reproducibility as previously demonstrated 2.4The 4-chamber view showing all 4 cardiac chambers was used to calculate LA and RA strain and strain rate The three main components of atrial physiology were quantified as follows A and B: 2.5Ventricular strain was calculated from horizontal long axis and short-axis slices as previously described Volumetric analysis was performed with commercially available software . For EA patients the functional right ventricle (fRV) was used for RV measurements and contours were drawn to the insertion of the displaced TV leaflets. For ventricular volumetric analysis, endocardial contours for RV and LV were drawn in all short axis slices at end systole and end diastole. Short axis orientation was employed deliberately since previous work has demonstrated similar results for short axis and transverse quantification of ventricular function The Total Right/Left-Volume-Index (R/L-Volume-Index) as a clinical severity parameter of EA was calculated from end diastolic volume measurements 2.6t-test and the Mann-Whitney-U test for parametric and non-parametric data, respectively. Spearman's correlation coefficients were calculated for relations between functional indexes and heart failure parameters and for relations between the functional indexes of atria and ventricles. A sub-group analysis was performed after exclusion of EA patients with previous corrective surgery (24 patients left).Statistical analysis was performed using Microsoft Excel , Statistica  and IBM SPSS Statistics version 22 . Data are expressed as mean (± standard deviation). After assessment for normality using the Kolmogorov-Smirnov test, the data were compared using a p-values for Spearman's correlation were reported for descriptive purposes. For all other comparisons, p-values < 0.05 were considered statistically significant.Measurements were performed by two independent skilled observers. The first observer (M.B) analysed all data based on average curves of three analyses repetitions and repeated the analyses of the functional atrial parameters in 10 randomly selected subjects after a period of 4 weeks for the intra-observer variability. The second observer (J.T.K.) performed the analysis in the same 10 subjects for the analysis of the inter-observer variability. Reproducibility was assessed using the coefficient of variation 3p = 0.238).CMR-FT was successfully performed in 30 patients with EA and all controls. One patient with EA was excluded due to insufficient image quality from motion artifacts. The mean age of the EA patients was 26.3 years ; 2) atrial conduit function (RA εe and SRe) correlated with the R/L-Volume Index; and 3) atrial booster pump function (RA εa and SRa) correlated with NYHA class and BNP (see RA function exhibited correlations with heart failure parameters in EA patients see : 1) atri BNP see .Table 2CThere was no significant correlation between RA deformation parameters and the degree of TVR.3.2RV volume was higher, and RVEF and RV longitudinal strain (RV εl) were significantly lower in EA patients compared with healthy controls see .3.2.1RV volume and RVEF correlated with the R/L-Volume Index. RV εl correlated with all heart failure parameters  see .3.2.2Atrio-ventricular coupling analysis revealed correlations of RV εl with atrial reservoir and conduit function see .Table 3C3.3EA patients had decreased LA reservoir (εs) and conduit function  as well as reduced booster pump function (SRa) see .3.3.1r = − 0.455, p = 0.017 and SRa r = 0.455, p = 0.017).LA booster pump function showed a correlation with NYHA class based on strain and SR, respectively (NYHA–LA εa 3.4p = 0.067), while LV volumetric parameters did not differ between groups.There was a trend towards lower LV longitudinal strain (LV εl) in EA patients compared to controls .LV volumetric data correlated with NYHA class and the R/L-Volume-Index .The correlation of heart failure stages with both reservoir function  and booster pump function (NYHA) remained, irrespective of the exclusion of the patients who underwent corrective surgery (data not shown). Conversely, the association of RA booster pump function and BNP could not be detected when looking at the EA subgroup without previous cardiac surgery  and RA conduit function.3.6Atrial strain and SR were reproducible on an inter- and intraobserver level with low values for mean difference and coefficient of variation .4Our study describes a well-characterized, functional phenotype based on atrial and ventricular mechanical function in EA. We demonstrate that CMR-FT is a suitable technique for quantification of cardiac atrial and ventricular deformation in a complex congenital heart malformation such as EA. We can show for the first time, that in EA CMR-FT derived RA and RV function, but to some extent also LA function, was impaired and correlated with heart failure markers. Correlation analysis of RA function with heart failure markers revealed the following: 1) patients with more severe heart failure stages (expressed by BNP and NYHA class) showed larger reduction of RA reservoir function and RA booster pump function, and 2) patients with more severe EA (as expressed by the R/L-Volume-Index) had lower values for RA conduit function.It is important to note, that these findings were independent of previous cardiac surgery and are thus applicable to a heterogeneous EA patient collective. Moreover, it is important to understand that RA function is dependent on loading conditions and RV and tricuspid valve function at the time of the exam. Changes in RA function are not necessarily reflective of overall intrinsic atrial function alone.Besides functional impairment of the RA, LA conduit function was also affected to a lesser extent. Interestingly, whilst LA reservoir and conduit function were lower as compared to control subjects only LA booster pump function was related to heart failure severity as defined by NYHA. This is paralleled by association of reduced RA booster pump function with NYHA class in our cohort. Similar to findings in non-congenital left heart disease 4.1Standard RV functional parameters derived from CMR including EF and volumes do not correlate well with exercise capacity and heart failure markers in EA patients Quantification of RA function in CHD is receiving increasing interest The mechanism behind impaired RA deformation might be a higher degree of RA preload (determined by a) central venous return and b) TR induced volume load) and an unfavourable pre-dilation of atrial myofibres (Frank-Starling mechanism). Changes in atrial strain and strain rate, as observed in our study, are reflective of contractility and distensibility of the myofibrils, i.e. possibly alterations in the optimal Frank-Starling curve. A study of Ren et al. links changes in LA function in patients with mitral regurgitation to the Frank Starling Mechanism and atrial pre-load conditions RV function in EA patients was also compromised, as expressed by impaired RV εl. Changes in RV εl depict changes in RV myocardial contraction and are – comparable to RA function – dependent on ventricular loading conditions. However, RV εl correlation with heart failure markers suggest that these changes in deformation may be clinically relevant.Unifying the above observations, we hypothesized that cardiac dysfunction in EA is linked to decreased RA deformation – possibly based on a shift away from the optimal Frank-Starling curve – coupled with impaired RV longitudinal function (i.e. reduced RV εl in the EA group). Spearman analysis of RA–RV interaction in our cohort confirmed positive correlation of RV strain with RA reservoir and conduit function and supports this hypothesis.4.2Our results show that LA function is also affected, albeit to a lesser extent compared to the RA, while LV systolic function was normal. Even though systolic LV function may be preserved in our collective, LA reservoir and conduit function are reduced and may reflect LV diastolic dysfunction. This hypothesis is in line with Inai's description of diastolic dysfunction in EA with preserved LV EF 4.3This was a single center cross sectional study. Our cohort only comprises a small number of patients with higher degree heart failure (NYHA III or IV), which is due to the low incidence of EA.To discern the role of the RA conduit function further, CMR-FT analysis of both the RA and aRV would be necessary. However, since CMR-FT relies on tracking myocardial borders and the aRV lies within the fRV only separated from it by the malformed TV, there are no myocardial borders that can be tracked by CMR-FT. This makes CMR-FT analysis of the aRV technically impossible.Finally, age-wise maturation of atrial function have been reported in the echocardiography literature 5aRVatrialized right ventricleASDatrial septum defectBNPbrain natriuretic peptideBSAbody surface areaCHDcongenital heart diseaseCMRcardiovascular magnetic resonance imagingεstrainεccircumferential strainεllongitudinal strainεaatrial active longitudinal strainεeatrial passive longitudinal strainεsatrial total longitudinal strainεrradial strainEAEbstein's AnomalyEDViend diastolic volume indexed to body surface areaEFejection fractionESViend systolic volume indexed to body surface areafRVfunctional right ventricleFTfeature trackingLAleft atriumLVleft ventricleNYHANew York Heart AssociationRAright atriumR/L-Volume-IndexTotal-Right/Left-Volume-IndexRVright ventricleSRstrain rateSRaatrial peak late negative strain rateSReatrial peak early negative strain rateSRsatrial peak positive strain rateTOFTetralogy of FallotTVRtricuspid valve regurgitationTVtricuspid valveRight atrial and ventricular myocardial strain and strain rate are reduced in EA and can be reliably quantified using CMR-FT. CMR derived longitudinal right atrial and ventricular strain appear to be markers of heart failure in EA, since a close correlation of these parameters with NYHA class, BNP and R/L-Volume-Index was observed. Alterations in LA function were also noted. Incorporating atrial and ventricular deformation indices into CMR assessment may help to improve the management and decision making for intervention or operation in EA patients.The authors report no relationships that could be construed as a conflict of interest.None.


In this issue of the journal, Sammani et al. describe 30 years of heart transplantation in Utrecht . It is rAny form of organ transplantation still evokes that feeling of a high, innovative technology. Heart transplants are no exception. It is a therapy that is used only very rarely, and hence it is by definition very special. However, although hard to imagine it has been around so long it can be regarded as part of mainstream medicine. As we are all well aware, the first human heart transplant was done by Dr Christiaan Barnard already in December 1967, when he transplanted the heart of a 23-year old brain-dead woman into a 57-year-old recipient. Three years later more than 150 heart transplants had been performed worldwide. However, in these early days the ability to match donor and recipient was limited and the immune reaction could only be suppressed by corticosteroids. Hence, most – if not all – transplantations in those days failed quickly so that widespread disappointment made most abandon this idea altogether. As with many novel technologies, an additional innovation was needed to make organ transplantation feasible. This was the development of stronger and more selective immune suppression. Cyclosporine was discovered and developed by Jean Borel and colleagues in the 1970s [It is, therefore, not surprising that in that decade the first heart transplant in the Netherlands took place at the Dijkzicht Hospital in Rotterdam in 1984, so that we have now seen more than 30 years of heart transplantation in the Netherlands.As with many big strides in science, behind the fame and recognition of the first heart transplant is the race between competing researchers with often strange twists of fate that decide its outcome.In fact, the same Christiaan Barnard had spent weeks in the laboratory of the American surgeon Richard Lower to watch how Lower had developed his technique to transplant hearts between dogs. Lower and his research partner, Dr Norman Shumway, had been close to performing the first heart transplantation on a number of occasions, but had to cancel due to donor-recipient incompatibilities. Back in South-Africa, Barnard spent months trying to establish Lower’s technique in his own lab, but the dogs he transplanted would die within days. Nevertheless he went ahead and did the human transplant anyway, while Lower and Shumway had to wrestle with more stringent transplant legislation in the US. And, as we know, although the recipient unfortunately survived the transplant only briefly, Barnard was designated the pioneer of human heart transplantation.Adding to the irony was that Lower later had to face a million dollar lawsuit for allegedly taking out the heart of a donor too soon . This also illustrates the other side of the coin , where ethical issues are clearly a major part of the debate surrounding the technology. For instance, in the early 1990s, there was no legislation on brain death in Japan and heart transplantation was still strictly prohibited there .In the Netherlands, the two main centres for heart transplantation are Utrecht (with around 5 transplants done yearly in Groningen) and Rotterdam. Together around 50 transplantations are performed yearly and it is clear that this number does not suffice to serve the population of patients with end-stage heart failure.With the improvements made in assist devices, they are quickly taking an important place not only to gain time as patients await their transplantation, but increasingly as destination therapy.As a result it is justified to wonder if we will still be transplanting hearts in 2048. When the external drive-lines of assist devices are no longer needed, and assist devices go through the next rounds of improvements, major problems such as infection, thrombosis and bleeding may be better managed. Then these artificial hearts may even replace heart transplantation all together and heart transplantation will again be overtaken by the next wave of innovation.