The purpose of this study was to evaluate the measurement of heart rate undertaken in clinical studies by (1) assessing the repeatability and reproducibility of heart rate measurements by various methods and under various conditions and (2) determining whether a single heart rate measurement at rest is representative of the circadian and inter-day variation of heart rate.Prospective cohort study in 102 patients with various types of heart disease at Duisburg Heart Center, Germany between 2011 and 2012. The heart rate measurements were based on self-assessment, ECG tracings at rest, and bicycle stress ECG in the office as well as 24-h Holter ECG.Office measurements and self-assessment at rest as well as 24-h Holter ECG and self-assessment at rest are highly correlated, but no correlation between self-assessment and office recordings/24 h recordings under exercise conditions was seen. Coefficient of variability was below 10 % for the self-assessment and for office measurements at rest. There were no differences in coefficient of variability during the day and within the 6 days for self-assessment of heart rate at rest and circadian variation was normal.At rest heart rate measurements by various methods agree sufficiently and inter-day/circadian variation is adequately represented. Under exercise conditions self-assessment of heart rate is not valuable and use of 24 h Holter as well as stress ECG recordings is necessary. Thus, self-reported heart rate measurements by the patient at rest seem to be reliable, but should be used in clinical studies only for heart rate assessment at rest. Previous epidemiological studies generated evidence for a correlation between heart rate and risk of cardiovascular disease and hence life expectancy in the general population and in patients with coronary heart disease (CHD) –4. Most In these studies, dose titration of heart rate lowering agents was primarily based on measurements of heart rate in ECG tracings at rest, occasionally on 24-h Holter recordings as well. Some studies simply relied on pulse counts obtained by the patients.The setting for the ECG recording was not specifically defined or described in the study protocols or other publications . FurtherWe therefore analyzed heart rate measurements obtained with various methods and at various points in time. Our primary objectives were (1) to assess the repeatability and reproducibility of heart rate measurements by various methods and under various conditions and (2) to determine whether a single, casual heart rate measurement at rest is representative of the heart rate pattern during the day and between six consecutive days. Furthermore, data collected might shed light on the issue, whether self-reported heart rate measurements by the patient are reliable and, therefore, can be used for heart rate assessment in clinical studies.This investigation was a single center, prospective cohort study in 102 patients aged 42–80 years with various types of heart disease treated according to ESC and National Guidelines , 10. PatVariability in heart rate during the day and day to day variability were analyzed and compared to the heart rate recorded by the ECG at rest in the clinic (office) based on coefficient of variability, repeatability, and reproducibility. Change and reproducibility provide values of the upper limits for the variation with high probability (that is for the difference between repeated measurements). In order to compare self-assessments and the heart rate recorded by the ECG at rest in the clinic, Holter recordings and stress ECG, heart rates agreement was used and defined as a deviation of less than 10 beats/min from mean. For the visual analysis of the 24-h heart rate pattern, we defined a tachycardia period as the duration in time of heart rates deviation of more than 10 beats/min from mean.Measurements recorded during the ambulatory period were stored on a personal computer and screened for artifacts as defined by previously described criteria . Only ret test. Consistency was obtained by calculating the difference between baseline and repeat recordings, disregarding the sign of the difference.Categorical variables are described by using percentages and absolute numbers, continuous variables by using mean, standard deviation, and range. The Brevais-Pearson coefficient was used for correlations, and reproducibility was assessed using the Bland-Altman approach . Change Repeatability was defined as twice the standard deviation of the changes between two repeated recordings. To compare the reproducibility of different variables, the maximal biological variation (MBV) of the variables was calculated  . All staThe clinical characteristics of the patient population are shown in Table According to the protocol, we expected the patients to record six measurements at rest during the day for a total of 6 days and three measurements per day under exercise conditions. For consistency reasons, we used only self-measurement of heart rate with corresponding Holter recordings and office treadmill heart rate measurements for statistical analyses. Therefore, the number of observations read for the analysis of heart at rest assessed by self-assessment was 3559 in total and 3474 were used. Similarly, for the comparison of heart rate under exercise conditions assessed by self-assessment, the number of observations read was 1831 in total and 1620 were used. Heart rates measured under various conditions are reported in Table Change, consistency, repeatability, mean biological variability (MBV), and coefficient of variability for heart rate measured at rest in the office and with self-assessment are reported in Table Due to the study design (only one 24-h Holter recording was performed), we used heart rates agreement defined as a deviation of less than 10 beats/min from mean in order to compare heart rates under the various conditions. Maximum heart rates in Holter recordings during daytime will correspond to exercise in a patient under adequate heart rate controlling medication and minimum heart rate will correspond to rest Table . Compari60 % of patients showed tachycardia periods with a duration of less than 25 % of the time recorded  during the 24 h,38 % of patients presented tachycardia periods with a duration of 25 to 50 % of the time recorded  during the 24 h and,only 2 % of patients had tachycardia periods with a duration of 50–75 % of the time recorded  during the 24 h. During the sleeping hours, the registered tachycardia periods encompassed 12.4 % of the time recorded (range 0–52.2 %).Analyzing the 24-h heart rate pattern for tachycardia periods, we observed the following:The study included 15 patients with atrial fibrillation. All of them were already diagnosed with atrial fibrillation and no newly diagnosed atrial fibrillation was detected. Twenty percent (3/15) presented with permanent fibrillation and 80 % (12/15) with paroxysmal fibrillation. In the patients with paroxysmal fibrillation, 9/12 patients showed sinus rhythm, 2/12 patients had permanent fibrillation, and 1/12 patients showed only short phases of atrial fibrillation on 24-h Holter recordings. Analyzing the 24-h heart rate pattern for tachycardia periods, we observed the following: (1) 7/15 patients showed tachycardia periods with a duration of less than 25 % of the time recorded  during the 24 h, (2) 7/15 patients presented tachycardia periods with a duration of 25 to 50 % of the time recorded  during the 24 h, and (3) only 1/15 patients had tachycardia periods with a duration of 50–75 % of the time recorded (range 56.7 %) during the 24 h. In the subgroup of the three patients with permanent atrial fibrillation 2/3 patients showed tachycardia periods with a duration of less than 25 % of the time recorded and 1/3 patients tachycardia periods with a duration of 25 to 50 % of the time recorded. In the subgroup of patients with paroxysmal atrial fibrillation, 6/12 patients showed tachycardia periods with a duration of less than 25 % of the time recorded and 5/12 patients tachycardia periods with a duration of 25 to 50 % of the time recorded and 1/12 patients had tachycardia periods with a duration of 50–75 % of the time recorded.We hypothesized that the measurement of heart rate undertaken in clinical studies was not representative of (1) the circadian and inter-day variation and (2) of the exercise-induced variation of heart rate during the patient’s everyday life.Our hypothesis was only partially confirmed and we could show that the exercise-induced variation of heart rate during the patient’s everyday life is not adequately represented in clinical studies. Instead self-reported heart rate measurements at rest represent adequately the inter-day and circadian variation of heart rate. Self-reported heart rate measurements by the patient at rest are thus reliable, but can be used in clinical studies only for heart rate assessment at rest.Major part of this study is a measurement method comparison. The statistical aspects of measurement method comparisons have been thoroughly discussed by Altman and Bland , 14. AccNext, defining what is the normal resting heart rate and what is an acceptable deviation is troublesome. We based our decision on the following studies. First, in a study on resting heart rate in Diabetics with altered autonomic function, a standard deviation (SD) of to 10 beats/min was noticed in the healthy comparison group . In a muAnother limit of this study is the relatively small number of patients included in the study, but this is counterbalanced by the high number of observations used. Furthermore, we did not have a normal control group. However, this is not interfering with the objective of this study focused on the evaluation of heart rate measurement undertaken in clinical studies.As to our knowledge, there are no published studies on this argument and therefore comparison with the results of others may be only indirect and limited.In healthy individuals, there is a circadian pattern of heart rate with a peak heart rate around 10 am, and a gradual decline during the night with a nadir just prior to awakening . DiseaseFurthermore, atrial fibrillation might have an impact on the reproducibility of the various heart rate measurements. According to our results, atrial fibrillation was not a confounding factor due to fact that most patients in this study had only paroxysmal fibrillation with a majority of patients still showing sinus rhythm. In addition, analysis of the 24-h heart rate pattern for tachycardia periods showed that the results of patients with atrial fibrillation were comparable to patients with sinus rhythm.With regard to heart rate assessment under exercise or stress conditions, self-assessment underestimates the maximum heart rate patients are exposed to. This seems to be supported by the fact that peak exercise levels at home and during bicycle stress ECG were similar in a majority of patients. Thus, from a methodological point of view, bicycle exercise ECG as well as 24-h Holter recordings are more precise in documenting the maximum heart rates reached. Reasons for the above observation might be (1) the time delay between exercise and self-measurement and (2) the fact that the patients may simply have omitted the self-assessment in certain situations.Our study suggests that there is no pronounced variability of heart rate measurements taken at various time points neither during the day or at different days and, therefore, physiological variation in heart rate does not seem to be a confounding factor in the conduction of pharmacological intervention studies. With regard to the recording of the maximum heart rate under exercise or stress conditions self-assessment of heart rate is not a valuable neither a trustworthy method of investigation. Furthermore, heart rates registered point to relevant tachycardia under exercise or stress conditions. Noticeably in none of the intervention studies published so far, the maximum heart rate on heart rate limiting medication was documented. Based on the results of this study, we would recommend future studies to address the question, whether the extent of the heart rate limiting effect under exercise or stress conditions influences the end points such as cardiovascular morbidity and mortality.Dose titration of heart rate lowering agents in pharmacological intervention studies is actually based mostly on measurements of heart rate in ECG tracings at rest. In our study, heart rate measurements at rest in the office and based on self-assessment are comparable and reproducible. Physiological variation in heart rate does not seem to be a confounding factor in the conduction of pharmacological intervention studies. But under exercise conditions, heart rate measurements taken in the office and by 24-h Holter monitoring do not agree in a sufficient manor with measurements based on self-assessment.Consequently, self-assessment of heart rate provides the same information as conventional methods of measurement at rest. Under exercise conditions, the routine use of 24-h Holter as well as stress ECG recordings is helpful for a more complete data acquisition. Therefore, (1) self-reported heart rate measurements by the patient seem to be reliable only at rest and, therefore, should be used in clinical studies only for heart rate assessment at rest and (2) it seems reasonable to propose a standardized operating procedure for heart rate measurements in clinical studies comprising ECG tracings at rest during every visit (a minimum of three), three treadmill ECG, and three 24-h Holter recordings. Such common standardized operating procedure may enable the scientific community to compare more easily clinical studies without being limited by different methodological designs.


Cardiovascular complications are the main cause of death in chronic hypercorticism. Cushing's disease (CD) is caused by a benign pituitary gland secreting tumor resulting in endogen hypercorticism. Few ultrasound studies have described cardiac involvement in Cushing's disease, particularly left ventricular (LV) hypertrophy. Hypertrophy has been related to the often associated hypertension and little is known about the effect of high cortisol levels on ventricular mass and function. This is the first comprehensive description of biventricular and left atrial volumes and LV mass assessed by CMR in hypercorticism compared to matched controls. Furthermore, the reversibility of the cardiac phenotype associated with hypercorticism was evaluated after treatment.This is a longitudinal monocentric case control study. All CMR exams were performed between from 2010 to 2013 on 18 consecutive CD patients and 18 asymptomatic controls matched on age, body mass index, and blood pressure range. First CMR was performed upon initial diagnosis and a follow-up exam was done on average 8 months after surgical treatment. Right and left ventricular and atrial volumes, left ventricular mass, thickness, were quantified on SSFP cine CMR and normalized by body surface area. Biventricular and left atrial ejection fractions were calculated. 24-hour urinary free cortisol and glycemia were recorded.No patients were lost to follow up. Compared to controls, baseline right and left ejection fractions were significantly altered in CD patients  mainly due to increased end systolic right and left ventricular volumes in CD patients . Left atrial ejection fraction was significantly lower among CD patients . Average LV wall thickness was markedly increased in basal, mid-ventricular and apical segments . After treatment, 24-hour urinary free cortisol was normalized . LV mass decreased , LV and RV stroke volumes increased  and left atrial and ventricular function improved . No death or intercurrent cardiovascular event was observed during the study period.CMR allowed to demonstrate infraclinical biventricular cardiac involvement in Cushing's disease with systolic ventricular and atrial dysfunction and concentric LV remodeling that were largely reversible after radical treatment.This study was funded by Université Paris Descartes (V), and by Université Paris Sud.


Objectives. To investigate changes in pulsograph caused by pain in primary dysmenorrhea (PD) patients. Methods. Pulsograph and pain level of PD patients were detected using electropulsograph and Visual-Analogue Scale (VAS), respectively, at four time points, 7–10 days before menstruation (T0), maximal pain during menstruation (T1), immediately after acupuncture analgesia (T2), and 30 mins after acupuncture analgesia (T3). Parameters  and normalized time parameters (t′) of pulsograph were analyzed. Results. VAS pain scores decreased from 6.40 ± 1.13 at T1 to 0.70 ± 0.75 at T2 to 0.11 ± 0.32 at T3 (P < 0.001 and 0.001). At T1, compared with those at T0, w1, h3, and h4 significantly increased (P < 0.01), and t2, t2′, t3′, and h(d) significantly decreased . At T2, compared with those at T1, t1, w1, w2, h2, h3, t1′, and t4′ significantly decreased , and h(d) significantly increased (P < 0.001). There was no difference between T2 and T3. Conclusions. There are almost opposite changing trends in pulsographic parameters when pain occurs and when it is relieved in PD patients. The cunkou at each hand is divided into the following three portions, respectively. The guan position is in the middle part of cunkou, just near the radial styloid process, cun portion between the wrist crease and guan portion, and chi portion on the other side of guan portion. By feeling the pulse condition, TCM clinicians may know the unique TCM pattern status of the human body [Pulse assessment is an assessing method used in Traditional Chinese Medicine (TCM). The main site for pulse feeling is the radial artery located in the inner side of radial styloid process at wrist, also calledman body .Diagnostics of TCM, a textbook widely used at TCM colleges and universities which is about how to examine illness and recognize syndrome in TCM, recorded that pain is often accompanied by wiry pulse, tight pulse, or tremulous pulse [us pulse . Clinicaus pulse .h1, h3, h4, and h5 of pulsograph during menstruation between different TCM patterns of 148 PD patients [In view of the subjectivity of clinicians' pulse feeling, increasing interest has been focused on pulse apparatus where sensors are developed to acquire pulse signals. Pulse apparatuses are exploited to analyze pulse conditions . Recentlpatients .Pain affects pulse conditions, giving rise to pulse changes. Accordingly, we designed the current research to investigate the pain-induced changes in pulsograph parameters. Primary dysmenorrhea (PD) is a common disease in young women. In view of its regular episode and quick relieving after treatment we chose PD representing pain to provide a basis for further study on pulse condition associated with pain in TCM.From April 2014 to May 2014, college students in Beijing University of Chinese Medicine who were aged 18 to 30 years with dysmenorrhea with pain level reaching 5 scores on a Visual-Analogue Scale (VAS) within the previous 3 regular menstrual cycles were recruited. PD patients who were diagnosed by the follow-up clinical examinations were invited to participate in the study. The diagnosis was made according to Primary Dysmenorrhea Clinical Guidelines made by Society of Obstetricians and Gynecologists of Canada (SOGC) in 2005. Accordingly, all patients had periodical pain in the lower abdomen before or during menstruation with normal pelvic examination and ultrasound . cunkou.Since unnatural changes of body may impact pulse , we exclT0), maximal pain during menstruation (T1), immediately after acupuncture analgesia (T2), and 30 mins after acupuncture analgesia (T3).We observed PD patients at 4 time points: 7–10 days before menstruation  and gorge of main wave  and peak of the prodicrotic wave  and dicrotic notch , width of the upper 1/3 (w1) and 1/5 (w2) of the main wave, the time of dicrotic wave (t(d)), and amplitude of the peak of dicrotic wave (h(d)).In this study pulsograph was detected by DS01-C electropulsograph where baroreceptors were developed to acquire pulse signals produced by Shanghai Daosheng Medical Limited Company. The pulse signals were converted into pulsograph through a computer system. The characteristics extraction and analysis of pulsograph were done by using the time-domain technique . As showCunkou is the main position for pulse feeling in TCM and also is the only part which electropulsograph can detect. TCM holds that left cunkou can better show the body situation of women because it mainly reflects the situation of heart, liver, and kidney. In addition, left cunkou can avoid the influence on the pulse by different motion styles in right-handed individuals. Electropulsograph only has one probe and guan position is more easily to be accurately detected. So pulsograph of guan position of left cunkou was detected in this study.T0, T1, T2, and T3. Specific detection method was as follows: patients were required in supine position, with forearm stretched, wrist straight, palm up, and wrist at the same level with heart. Trained experimenter fixed the probe of collector at the guan position of left cunkou. The computer would collect pulsographs of different pressures when the patients were relaxed and breathed naturally and then select the best pulsograph automatically for analysis.Pulsograph was detected at Previous researches prove that acupuncture has instant analgesic effect  and is oT1. Selected acupoints included Sanyinjiao (SP6), Diji (SP8), and Yinlingquan (SP9), on both sides [Acupuncture was initiated at th sides . Manipult-test. Differences with P < 0.05 were considered statistically significant. The statistical evaluation was performed by using the statistical software package SPSS 17.0.Measurement data were presented as mean ± standard. The measurement data were analyzed by 30 patients with PD were enrolled with a mean age of 23 years , and with an average suffering time of 7 years . All the patients had provided written informed consent before completion of the experiment between May and August 2014.T0. At T1, patients experienced the maximal pain, and the reading on the VAS increased drastically to 6.40 ± 1.13. With acupuncture analgesia, compared with the reading at T1, VAS pain scores significantly decreased to 0.70 ± 0.75 at T2 (P < 0.001). After acupuncture analgesia, the pain scores at T3 significantly decreased to 0.11 ± 0.32 (P < 0.001), compared with that at T2.As shown in T0 to T1, time of peak of the main wave (t1) increased (P > 0.05) and amplitude of peak of main wave (h1) decreased (P > 0.05) (t2) decreased significantly (P < 0.05) and amplitude of gorge of the main wave (h2) increased (P > 0.05) (t3) decreased (P > 0.05) and amplitude of peak of prodicrotic wave (h3) increased significantly (P < 0.01) (t4) increased (P > 0.05) and amplitude of dicrotic notch (h4) increased significantly (P < 0.01) (w1) and 1/5 (w2) of main wave both increased (P < 0.01 and P > 0.05) (From  > 0.05) . Time of > 0.05) . Time of < 0.01) . Time of < 0.01) . Widths  > 0.05) .T1 to T2 to T3, t1 decreased gradually and there was statistically significant difference between T1 and T2 (P < 0.05). Meanwhile, h1 increased gradually and was significantly higher at T3 than at T1 (P < 0.05) (t2 increased (P > 0.05), while h2 significantly decreased (P < 0.05) at first and then increased (P > 0.05) (t3 increased at first (P > 0.05) and then decreased (P > 0.05), while h3 significantly decreased (P < 0.001) at first and then decreased (P > 0.05) (t4 increased (P > 0.05), while h4 decreased (P > 0.05) at first and then increased (P > 0.05) (w1 and w2 demonstrated significant reductions at first (P < 0.01) and then had no significant changes (P > 0.05) (From  < 0.05) . t2 incr > 0.05) . t3 incr > 0.05) . t4 incr > 0.05) . Both w1 > 0.05) .T0 to T1, time of the peak of dicrotic wave increased (P > 0.05) and amplitude of the peak of dicrotic wave (h(d)) significantly decreased (P < 0.001). From T1 to T3, t(d) increased (P > 0.05), while h(d) increased significantly (P < 0.001) firstly and then increased mildly (P > 0.05).As shown in T0 and decreased to 69.63 ± 6.24 times/min at T1 (P > 0.05). After acupuncture treatment, heart rate significantly decreased to 66.53 ± 6.94 times/min at T2 (P < 0.01) and increased to 67.63 ± 9.14 times/min at T3 (P > 0.05) (Heart rate was 71.930 ± 11.22 times/min at  > 0.05) . t′. The comparison of t′ results after normalization is shown in T0, there was no difference in t1′, t4′, and t(d)′ (P > 0.05) at T1. Meanwhile, t2′ and t3′ significantly decreased from T0 to T1 . From T1 to T3, t1′ and t4′ significantly decreased at first (P < 0.001) and then remained unchanged (P > 0.05). And there was no significant change in t2′, t3′, and t(d)′ from T1 to T3 (P > 0.05).In view of the fact that time parameters will be effected by different heart rates, in this paper, time parameters of pulsograph at 4 time points were normalized at 75 times/min heart rate and named as blood stasis blocking the uterus. That is to say, during menstruation, qi and blood fail to flow freely. Pain arises as a result. Apart from pain, changes in movement of qi and blood would also affect cunkou pulse [Primary dysmenorrhea (PD) is defined as a cramp-like pain in the lower abdomen before or during menstruation without any identifiable pelvic pathology. Pain may be accompanied by lower back pain, nausea, vomiting, and diarrhea. PD is frequently found in young nullipara . Modern ou pulse . cunkou pulse before dysmenorrhea and in obvious dysmenorrhea and after dysmenorrheal relieving in PD patients were investigated. Considering effect of different heart rates on the time parameters of pulsograph, in this experiment, the time parameters were normalized at the heart rate of 75 times/min. In so doing, we were more inclined to think that normalized time parameters could better reflect the effect of pain on time parameters in PD patients.In this study, pulsographic parameters ofT0 to T1) and finally to after dysmenorrheal relieving (from T1 to T2). Although the effect of menstruation on pulsographic parameters cannot be excluded from T0 to T1, combining with the changes from T1 to T2 we can come to a preliminary conclusion that pain could cause increases in width of the upper 1/3 of main wave (w1), in amplitude of gorge of main wave (h2), and in amplitude of dicrotic notch (h4) and decreases in time of gorge of main wave (t2) and in amplitude of peak of dicrotic wave (h(d)).Changes in pulsographic parameters revealed almost opposite changing trends from before dysmenorrhea to before dysmenorrhea (from T1 to T2 and from T2 to T3). Part of parameters showed continuous similar changes. For example, t1 kept decreasing and h1, t4, t(d), and h(d) kept increasing. Some changes from T1 to T2 and from T2 to T3 were in opposite directions. For instance, h3 and h4 increased at first and then decreased, and t3 decreased at first and then increased. Still others changed significantly from T1 to T2 but no obvious changes from T2 to T3 were observed, such as w1 and w2, which decreased at first and then almost did not change. The possible reason for this phenomenon may be related to the negative feedback regulation which caused corresponding changes in the radial artery.Interestingly, we also noticed different changing trends from the commencement of acupuncture to 30 mins after acupuncture (from Previous researches show that each pulse is of specific pulsograph features. The changes in pulsographic parameters in our research could be interpreted with reference to wiry pulse, slippery pulse, and forceful pulse. The pulsograph of wiry pulse is characterized by higher prodicrotic wave, close to or fused to the main wave, manifesting as a broad single peak main wave, and higher dicrotic notch, and flat dicrotic wave. The pulsograph of slippery pulse is characterized by a higher double-humped main wave with big-slope ascending and descending branches, and a delayed prodicrotic wave, and a higher dicrotic wave. In addition, pulsograph of forceful pulse is characterized by a higher main wave . In thisAs a pilot study we have to admit that there are some limitations in this study. Firstly, a limitation was the small number of enrolled patients and lack of control group. Without control group of healthy females, influence of menstruation on pulsograph could not be excluded. Secondly, the pain of PD cannot represent all kinds of pain owing to its localization and patient population particularity. Further studies on different types of pain influencing pulsograph are needed before we can know for sure how pain affects pulsographic parameters.There are changes in pulsographic parameters, basically in opposite trends, in patients with PD when their pain occurs and when it is relieved. Further studies with control groups are needed to determine whether pulsographic parameters can be used as an objective indicator for pain changes in patients with primary dysmenorrhea.


Cardiotoxicity from cancer chemotherapy is an important cause of morbidity and mortality in breast cancer survivors. Left ventricular (LV) systolic dysfunction due to sequential use of anthracyclines and trastuzumab has been reported in up to 20-25% of patients. The pathophysiological changes associated with LV dysfunction have not been described non-invasively. We performed cardiac MRI (cardiac MR) with T2 mapping to assess whether myocardial edema is a feature of acute cardiotoxicity in women with breast cancer receiving sequential anthracyclines and trastuzumab.We prospectively recruited women with HER2+ breast cancer scheduled to receive anthracyclines followed by trastuzumab (Grp A) and patients during therapy with anthracyclines and trastuzumab who were diagnosed with subclinical cardiac toxicity (Grp B) using multi-gated acquisition scans (MUGA) based on Cardiac Review and Evaluation Committee's criteria. All patients (July to Aug 2013) underwent cardiac MR imaging at 1.5 Tesla with conventional steady state free precession cine and late gadolinium enhancement (LGE) imaging with addition of quantitative T2 mapping using a T2-prepared single-shot SSFP technique. LV volumes and systolic function were quantified and segmental T2 values for all 16 myocardial segments were obtained from basal, mid, and apical short axis views. T2 values > 59 ms were considered abnormal based on previously published data. Mann-Whitney rank sum test was used for comparisons.Preliminary results: Patients in Grp A  had higher LVEF than patients in Grp B  - 59 ± 7% vs. 49 ± 5%; p = 0.02. While all segments n = 96; 100%) in patients in Grp A showed T2 values < 59 ms with a mean of 53.6 ± 2.9 ms (47.5-58.8 ms), in patients in Grp B 14/48 segments (29%) showed abnormal T2 values > 59 ms with a mean of 63.5 ± 4.2 ms (59.4-70.9 ms); p < 0.001. The remaining 34 segments in patients in Grp B demonstrated T2 values < 59% with a mean of 55.2 ± 2.3 ms. Two out of the 3 patients in Grp B had minimal mid-myocardial scar on LGE imaging. Figures 00% in paThis preliminary analysis of a larger ongoing study demonstrates significant increase in segmental T2 values in breast cancer patients with cardiotoxicity compared to those pre-initiation of chemotherapy. This suggests that myocardial edema may be a feature of cardiotoxicity that results from treatment with sequential anthracyclines and trastuzumab. Whether quantitative assessment of myocardial edema early during therapy can predict subsequent development of cardiotoxicity remains to be determined.Grant Miller Cancer Research Fund.


T1 mapping and extracellular volume (ECV) imaging are promising tools to quantify increased extracellular distribution volume of contrast media after myocardial damage. We evaluated the ability of ECV imaging to measure infarct size compared to late gadolinium enhancement (LGE) after acute myocardial infarction (AMI). Additionally, the amount of cellular damage was serially measured by ECV imaging.CMR (1.5 Tesla Philips Achieva) was performed in 11 patients four times after reperfused AMI at baseline (BL) at 10 ±7 days after infarction and at 7.2 ±1.4 weeks , 3.4 ±0.3 months (FU2) and 6.5 ±0.5 months (FU3), respectively. T1 quantification was performed before (T1pre) and 15 minutes after (T1post) administration of 0.075 mmol/kg gadolinium BOPTA on 3 short-axes for ECV calculation using the modified Look-Locker inversion-recovery (MOLLI) sequences. T1 and ECV maps were calculated with a dedicated plug-in written for the OsiriX software. Two experienced observers independently evaluated LGE-CMR as well as T1 mapping using the HeAT-Software applying a threshold method. Size of infarction and areas of prolonged post T1 or increased ECV was measured using a cutoff >2SD of remote normal myocardium.P=ns for all time points compared to LGE). ECV was 46±4% at BL and increased to 49±5% at FU1 (P<0.05) and remained constant at FU2 with 48±6% and 50±12% at FU3 (Figure Infarct size on LGE images was at BL 26 ± 8%LV and decreased to 21 ±10 %LV, 18 ± 10 %LV and 21 ±9 %LV at FU1, FU2 and FU3, respectively (Figure Similar infarct sizes were measured by LGE and ECV at four consecutive time points after AMI. ECV additionally gave information about the magnitude of cellular damage, which increased during infarct shrinkage. ECV enables to monitor infarct healing after AMI.This study is partially funded by the Deutsche Forschungsgemeinschaft.


Hereditary hemochromatosis, thalassemia and myelodysplastic sindromes represent iron toxicity models with evidence of iron-related heart failure. Non-Transferrin-Bound Iron (NTBI), plays a key role in the pathogenesis of cardiac toxicity leading to the production of reactive oxygen species which increase lipid peroxidation (MDA). In acute myocardial infarction (MI) microvascular obstruction (MVO) and hemorrhage (HEM) are independent predictors of left ventricular (LV) remodelling. HEM may be a source of iron toxicity through NTBI and pro-inflammatory mediators (IL-6) , which can directly contribute to acute impairment of myocardial function and adverse LV remodelling.The aim of the study was to assess NTBI in a consecutive cohort of patients (pts) prospectively enrolled with ST-elevation MI (STEMI).and its relationship with MVO and HEM.Fifteen pts with STEMI were enrolled if the onset of symptoms had been < 12 hours before PCI. NTBI, MDA and IL-6 were assessed at admission and at 0-3-6-9-12-24 hours. Cardiac Magnetic Resonance imaging (CMR) was performed on a 1.5 T scanner at 5 days and 6 months after the cardiac event. Myocardial edema and HEM were assessed by T2 and T2* mapping. MVO, myocardial salvage and necrotic area were assessed by early and late gadolinium enhancement (LGE).NTBI was detected in 13/15 pts with highest values in 4 pts with evidence of MVO and HEM. NTBI levels were significantly related to CK-MB and troponin T values. NTBI kinetic appears different in MVO and HEM (7/15 pts), with a peak values at 6 hours after PCI, in comparison with those with no evidence of MVO and HEM, in whom NTBI values were lower and remained indeterminable after the first 24 hours.The detection of elevated NTBI values in pts with STEMI, MVO and HEM suggest a possible role of iron cardiotoxicity in myocardial damage.None.


Different patterns of late gadolinium enhancement (LGE) including mid-wall fibrosis using cardiovascular magnetic resonance (CMR) have been reported in adult patients presenting with non-ischemic dilated cardiomyopathy (DCM). In these studies, LGE was associated with pronounced LV remodelling and predicted adverse cardiac outcomes. Accordingly, the purpose of our study was to determine the presence and patterns of LGE in children and adolescents with DCM.Patients <18 years of age presenting with severe congestive heart failure who were admitted for evaluation of heart transplantation at our centre underwent CMR examination which consisted of ventricular functional analysis and assessment of LGE for detection of myocardial fibrosis. Ischemic DCM was excluded by coronary angiography, and right ventricular endomyocardial biopsies ruled out acute myocarditis.2) and LV dysfunction (mean LV-EF 23 ± 8%) were examined. LGE was detected in 5 of the 31 patients (16%) appearing in various patterns characterized as mid-wall (n = 1), focal patchy (n = 1), RV insertion site (n = 1) and transmural (n = 2). Based on histopathological analysis, 4 of the 5 LGE positive patients had lymphocytic myocarditis, whereas one patient was diagnosed with idiopathic DCM.Thirty-one patients (mean age 2.1 ± 4.2 years) with severe LV dilatation (mean indexed LVEDV 136 ± 48 ml/mIn children and adolescents with DCM, focal histologically proven myocardial fibrosis is rarely detected by LGE CMR despite marked LV dilatation and severely depressed LV function. LGE occurred in various patterns and mostly in patients with inflammatory cardiomyopathy. It remains unclear whether myocardial fibrosis in childhood DCM reflects different endogenous repair mechanisms that enable favourable reverse remodelling. Larger trials are needed to assess the prognostic implications of LGE in childhood DCM. Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy in children and is characterized by a dilated and globally hypocontractile left ventricle. Childhood DCM is a heterogenous disease associated with high morbidity and mortality –3, especCardiovascular magnetic resonance (CMR) has gained an important role in the diagnosis of patients presenting with systolic heart failure. Late gadolinium enhancement (LGE) imaging enables identification and quantification of focal macroscopic myocardial fibrosis. In adult patients with non-ischemic DCM, various studies demonstrated not only a diagnostic but also prognostic role of LGE CMR –12. In tCMR assessment of myocardial fibrosis has been reported to be useful in patients with congenital heart disease , 15 and Patients under 18 years of age presenting with congestive heart failure who were admitted for evaluation of cardiac transplantation at our centre underwent CMR as part of our routine clinical examination. The diagnosis of DCM was made according to current guidelines: patients with a dilated left ventricle, defined by left ventricular end-diastolic dimension with a z-score of greater than 2 and an ejection fraction below a z-score of -2 were included in the study. Patients with congenital cardiac disease including abnormal origin of the coronary arteries or Kawasaki disease, neuromuscular or immunologic disease, familial cardiomyopathy, endocrine disorders, metabolic or mitochondrial disease and clinical evidence of acute myocarditis  were excluded.Clinical data were retrospectively obtained from hospital medical records including date of birth, gender, cause of DCM and age at CMR evaluation. Findings of the CMR studies were extracted from the routine clinical reports. Laboratory findings of B-type natriuretic peptide (BNP) and troponin I (TNI) at initial admission were also assessed. Clinical follow-up data of the patients included information about further treatment  and survival. Patients who were treated by medical heart failure therapy, follow-up data on echocardiographic data (LV dimension and function) were also assessed for the evaluation of reverse ventricular remodelling . The stCardiac catheterization was performed in all patients. Endomyocardial biopsies were performed in 30 of the 31 patients. In each patient two to three biopsies were taken from the RV interventricular septum using a transcatheter bioptome. In one patient there was no myocardial biopsy available, because myocardial perforation occurred at the first attempt of biopsy sampling with subsequent need for emergency surgery.2 (CD3+ T lymphocytes and/or CD68+ macrophages) in the myocardium, in addition to enhanced expression of HLA class II molecules.Histopathological analysis was performed as previously described , 18. EndAll CMR studies were performed on a 3-T system . Images were acquired with two sixteen-elements phased array coils. Sedation was applied in most of the patients.Images were acquired in supine position with two sixteen-elements phased array coils. Sedation was applied in younger patients when considered necessary. The CMR protocol included a stack of short-axis slices from the base of the heart to the apex using cine steady-state free precession (SSFP) with breath-hold or gradient echo (GE) sequences in free-breathing technique when patients were sedated. Data acquired during breath-hold were assessed with the following sequence parameters: TR 48 ms, TE 1.5 ms, flip angle 60°, slice thickness 6 mm, in plane image resolution 1.3 mm × 1.3 mm × 6.0 mm, temporal resolution 25-40 phases. In measurements during free-breathing, the sequence parameters were as follows: TR 56 ms, TE 2.5 ms, flip angle 12°, slice thickness 5 mm, in plane image resolution 1.4 mm × 1.4 mm × 5.0 mm. End-diastolic  and end-systolic  volumes, stroke volumes (SV) and ejection fractions (EF) for the RV and LV were calculated by dedicated software  after the RV and LV endocardial borders were traced manually at end-systole and end-diastole. All parameters were adjusted to body surface area (BSA).42, Circle Cardiovascular Imaging Inc., Calgary, Canada).Before administration of gadolinium, renal function parameters, i.e. glomerular filtration rate, as well as creatinine levels were assessed to exclude renal dysfunction. LGE was assessed after intravenous injection of gadopentetate dimeglumine  at a dose of 0.15 mmol/kg of body weight by using a two-dimensional inversion-recovery segmented gradient echo CMR sequence in the cardiac short and long-axis planes . The inversion time was adjusted for optimal suppression of signal from normal myocardium and the images were obtained within 5-10 min after injection (inversion time approximately 250-350 ms). All LGE images were interpreted accordingly to the American Heart Association 17-segment model. The patterns of LGE were classified as subendocardial-based, transmural, mid-wall striae, mid-wall patchy, subepicardial, RV insertion point and diffuse. Extent of LGE was assessed using certified software . A n = 21, 68%) were less than one year of age  months, median weight 6.6 (3-57) kg) were included in the study. The majority of patients  revealed DCM without and 16 patients (52%) with inflammation  corresponding to the diagnosis of chronic myocarditis  LVEDV was 136 ± 48 ml/mLGE was detected in 5 of the 31 patients (16%) appearing in various patterns characterized as focal patchy , transmural , RV insertion fibrosis (1 patient aged 1 month with lymphocytic myocarditis) and classic ‘mid-wall’   and showed a trend with increasing LV diameter   but not with LV-EF . RV parameters were not related to BNP levels. Significant correlations were found between LVEDVi and RV-EF , whereas LVEDVi showed no relationship with RVEDVi . No relationship was found between LV-EF and RV-EF .Levels of troponin I were related to the degree of LV dysfunction  Fig.  as a resThe detection of histologically proven focal myocardial fibrosis by LGE is uncommon (found only in 16%) although LV dilatation was marked and LV function severely depressed,The majority of LGE positive patients had chronic myocarditis suggesting a relation between histological signs of inflammation and LGE,Various patterns of LGE were found with transmural type of LGE being detected in two of the 5 patients, which is not typical for non-ischemic forms of DCM and might reflect embolic myocardial infarction.This study demonstrated that in young children and adolescents with dilated cardiomyopathyThe findings of our study are in contrast to previously reported CMR findings in adult patients with non-ischemic DCM where LGE was detected more frequently (in up to 50% of patients) and was associated with larger left ventricles, a higher degree of impaired function, elevated biomarkers and arrhythmias resulting in worse overall outcome –12, 20. In general, limited data exists about the pathogenesis of myocardial fibrosis in neonates, children and young adolescents with all types of cardiomyopathies including its assessment by LGE , 21–23. Specific patterns of LGE have been reported in patients with ischemic and non-ischemic DCM linking the type of LGE to a certain form of cardiomyopathy. In non-ischemic DCM mid-wall striae of LGE is known to be the typical finding, although various patterns such as focal patchy, subepicardial and diffuse LGE have also been described , 25, 26.The underlying mechanisms for the development of fibrotic changes in non-ischemic cardiomyopathies are related to different processes. Myocardial injury can be the result of different pathogens and toxins causing inflammation, individual genetic susceptibility, abnormal modulation of the immune system, permanent adrenergic activation and metabolic dysregulation –32. FurtThis suggests that the possible pathogenic factors and mechanisms leading to the phenotype of LV dilatation and dysfunction considerably vary in younger patients. Although speculative, the low incidence of myocardial fibrosis assessed by CMR might be related to differences in myocardial remodelling in DCM between children and adults. Nishikawa et al. analysed endomyocardial biopsies and found differences in the distribution of microscopic patterns of fibrosis, revealing a higher myocarditic index and a higher incidence of bizarre myocardial hypertrophy as well as discrete ultrastructural differences between adults and children with DCM , 36 suggDecision making whether cardiac transplantation is needed in the individual child with DCM is crucial but is hampered by a substantial rate of spontaneous recovery of ventricular dimension and function that has been described both in adult and childhood DCM , 39, 40.The small study population and the retrospective design of the study were accompanied by a selection bias towards patients presenting in an advanced stage of the disease who were referred for cardiac transplantation might not represent the entire population of children and adolescents with DCM. Therefore, the reported incidence of LGE as well as the observed rate of spontaneous recovery and outcome might differ in reality.Compared to previous studies, we observed a higher incidence of patients with myocarditis which must be considered when interpreting the data. The reason for this might be related to the fact that other causes for DCM, especially hereditary forms, were excluded in order to analyse a homogenous patients cohort. While the underlying genetic causes for childhood DCM are increasingly recognized , routineIdentification of LGE in very young patients may be limited by respiratory or motion artifacts related to spontaneous breathing under sedation. Furthermore, spatial resolution of the CMR sequence might be too low to detect small areas of local fibrosis in neonates and infants thereby underestimating its real prevalence. However, in a previous study in neonates and infants with ischemic DCM , LGE couIn children and adolescents with DCM, focal histologically proven myocardial fibrosis is rarely detected by LGE CMR despite marked LV dilatation and severely depressed LV function. LGE occurred in various patterns and mostly in patients with inflammatory cardiomyopathy. It remains unclear whether myocardial fibrosis in childhood DCM reflects different endogenous repair mechanisms that enable favourable reverse remodelling. Despite the small study population, our findings suggest that LGE may not be able to predict ventricular recovery or allowing reliable risk stratification as seen in adult patients. Nevertheless, the observed differences in incidence of myocardial fibrosis compared to adult patients may influence the therapeutic strategy in childhood DCM taking advantage of a less remodelled LV.


Endomyocardial biopsy is the gold standard for diagnosing viral myocarditis. However, this method is rarely used as it is more invasive, less sensitive and has a higher incidence of complications than other methods. With recent developments in myocarditis research, cardiovascular nuclear magnetic resonance imaging has been demonstrated to have a marked advantage over endomyocardial biopsy, specifically regarding the differential diagnosis of acute coronary syndrome, as it is noninvasive, repeatable, highly sensitive and highly specific for diagnosing myocarditis. Myocardial edema is characteristic of myocardial inflammation, myocardial necrosis and myocardial fibrosis. T2-weighted nuclear magnetic resonance imaging sensitively detects myocardial tissue edema and additional imaging parameters contribute to the diagnosis of myocarditis. Therefore, combining these methods with the current sophisticated electrocardiogram and coronary angiography examination methods may facilitate the rapid and accurate assessment of viral myocarditis. A 44-year-old male patient with symptoms of dyspnea and shortness of breath accompanied by dizziness, through electrocardiography, coronary angiography and magnetic resonance imaging, was diagnosed viral myocarditis. Myocarditis refers to a variety of myocardial inflammatory lesions. There are various causes of myocarditis, such as infection as well as physical and chemical factors, which result in myocardial damage of varying severity. The exact diagnosis of myocarditis requires histopathological evidence, which is predominantly obtained from endomyocardial biopsies. However, the diagnostic significance of endomyocardial biopsies during treatment is limited and is associated with certain surgical risks. Thus, it is not regularly used in current clinical treatments. The clinical manifestations of myocarditis differ due to variations in the degree of damage; thus, myocarditis is challenging to diagnose. For example, in a case where the history of viral infection is not clear and markers of myocardial necrosis are normal, the diagnosis of myocarditis is difficult to determine, regardless of clinical signs of heart damage, such as heart failure and arrhythmia. Therefore, a highly sensitive and accurate method is required to obtain a definitive diagnosis of myocarditis .At present, cardiovascular magnetic resonance imaging (MRI) is an important tool in the noninvasive assessment of patients with suspected myocarditis, specifically in the differential diagnosis of acute coronary syndrome (ACS). Cardiovascular MRI is used for diagnosing myocarditis, in addition to guiding endomyocardial biopsies ,3. The pA 44-year-old male patient was admitted to a local hospital one week subsequent to first presenting with symptoms of dyspnea and shortness of breath accompanied by dizziness, without severe chest pain, amaurosis or syncope. The electrocardiogram (ECG) demonstrated acute anteroseptal, right ventricular myocardial infarction, ventricular escape and a third degree atrioventricular block AVB; . EchocarThe results of the physical examination of the patient were: Body temperature, 36.5°C; heart rate, 62 bpm; respiratory rate, 18 breaths/min; and blood pressure, 120/70 mmHg. The patient was conscious, exhibited no lip cyanosis and had a soft neck with no jugular vein engorgement. Clear breath sounds were heard from both lungs, with no rales and the patient exhibited a negative hepatojugular reflux. In addition, no abnormal precordial bulge was observed and the apex beat was at the fifth intercostal space, 0.5 cm medial to the left midclavicular line. The heart rate was regular. No pathological murmurs or pericardial friction rubs were identified on auscultation and the patient was negative for any peripheral vascular signs. The abdomen was soft, with no tenderness or rebound tenderness, and no pitting edema was observed on either of the lower extremities.The Tn level was 0.053 ng/ml . Urinalysis, thyroid function, liver and kidney function were normal, as were the levels of blood glucose, blood lipids and electrolytes. Four days following admission to hospital, coronary angiography was conducted. This revealed normal openings and a running area without calcification in a right-dominant type coronary system in which: the left main coronary artery was without stenosis and had a forward flow of thrombolysis in myocardial infarction (TIMI) level 3; the left anterior descending had no significant stenosis and a forward flow of TIMI level 3; the left circumflex had no significant stenosis and a forward flow of TIMI level 3; the first obtuse marginal openings had visible plaques and a distal blood flow of TIMI level 3; and the right coronary artery had no significant stenosis, a forward flow of TIMI level 3 and no collateral circulation. On the basis of the imaging results, the diagnosis was coronary atherosclerosis. Six days following admission to hospital, the cardiac MRI revealed small, long T2 signals on the left anterior ventricular wall, which indicated slight edema . The patThe cardiovascular MRI of the patient indicated small, long T2 signals on the left ventricular anterior wall. This, in combination with the clinical manifestations and auxiliary examinations, such as the ECG, resulted in a diagnosis of myocarditis. Myocardial edema is characteristic of myocardial inflammation, myocardial necrosis and myocardial fibrosis, and can be detected via cardiac MRI . T2-weigIn 1999, the China Society of Cardiovascular Disease developed the adult acute viral diagnostic reference criteria as follows: i) Influenza, diarrhea and other viral infections occurred within three weeks of a cardiac event. ii) Arrhythmias or ECG changes observed within three weeks of infection, including the following; a) ventricular tachycardia, AVB, sinoatrial or bundle branch block, b) multi-source, paired ventricular premature atrial or ventricular flutter or fibrillation, and c) two or more horizontal or downward sloping lead ST segments ≥0.01 mV, ST segment elevation or abnormal wall motion. iii) Myocardial injury reference or wall motion abnormalities; a) significantly increased troponin T (TnT), troponin I (TnI) and creatine kinase-MB levels, b) ultrasound cardiography showing heart chamber enlargement, and c) radionuclide examination confirming left ventricular systolic heart function or diastolic dysfunction. iv) The etiological criteria for diagnosing myocarditis are as follows: 1) A virus, a virus gene fragment or a viral antigen in the endocardium, myocardium, pericardium or a pericardial puncture. 2) Antibody isotypes to the same pathogenic virus detected over two weeks in the serum, with the first determination four-fold higher than the second, or an antibody titer ≥640. 3) Virus-specific immunoglobulin M levels ≥1:320 are considered positive. Patients are clinically diagnosed with myocarditis if they exhibit any one of the criteria in 1 and 2 or any two of the criteria in 1, 2 and 3, excluding other symptoms. Etiological diagnosis is based on the clinical diagnosis, which includes one of the items among the criteria in iv. Severe viral myocarditis may be observed in patients with Adams-Stokes syndrome, heart failure or ECG changes, including myocardial infarction, cardiogenic shock, acute renal failure, ventricular tachycardia with hypotension or cardiac pericarditis as one or more of the manifestations.The majority of clinicians consider that conducting a endomyocardial biopsy is the gold standard for diagnosing myocarditis. The Dallas criteria describes lymphocyte infiltration with myocardial cell injury, but without myocardial ischemia; it has a high degree of specificity but a sensitivity of only 10–22% . Endomyocardial biopsies result in a greater number of complications, such as cardiac perforation and cardiac tamponade occurring in ~0.1–0.5% of patients, in addition to a variety of complications with an overall incidence rate of ~6% . The low sensitivity and risks that are associated with performing endomyocardial biopsies limit its use in the diagnosis of myocarditis; therefore, it is unsuitable for numerous patients with myocarditis, particularly those with mild myocarditis.et al , and is useful for guiding endomyocardial biopsies. Lurz et al  identifiet al , general myocardium-associated enhancement and late gadolinium enhancement (LGE) are specific parameters for detecting irreversible myocardial damage. Šramko et al  demonstrl (et al  investigl (et al  reportedPatients with myocardial injury usually demonstrate elevated markers, abnormal Q waves or ST segment changes in their ECG. However, myocardial infarction and myocarditis are complex to diagnose in atypical cases with no medical history or symptoms. Furthermore, when diagnosing myocardial infarction in younger patients, other diagnostic possibilities should be excluded. In such patients, coronary angiography or coronary computed tomography angiography are recommended to exclude coronary artery disease. When the coronary arteries of a patient are healthy, cardiac MRI may be considered, with signs of edema in T2-weighted imaging or evident focal high signal enhancement enabling a definitive diagnosis of myocarditis. Combined electrocardiography, coronary angiography and magnetic resonance imaging is a favorable method for the diagnosis of viral myocarditis, and it requires further cases to confirm.


The mechanisms responsible for atrial fibrillation (AF) maintenance are poorly understood. We studied the relationship between focal atrial fibrosis as assessed with late gadolinium enhanced (LGE) cardiac magnetic resonance (CMR), and the electrophysiological substrate of persistent AF as assessed with body surface potential mapping (BSM).We studied 41 patients with persistent AF . Patients underwent LGE CMR using an respiratory navigated and inversion recovery prepared 3D turbo FLASH sequence with fat saturation (pixel size 1.25×1.25×2.5mm), as well as non-invasive BSM during atrial fibrillation using a 256-electrode vest, enabling real-time panoramic mapping of atrial electrical activation. On CMR images, the bi-atrial wall was manually segmented and LGE was quantified using an adaptive histogram thresholding algorithm. The result was both a global quantification of LGE on the left atrial wall expressed in % of the wall and categorized according to Utah classification , and a patient-specific 3D map displaying LGE distribution on both atria. On BSM data, phase mapping was applied to visualize electrical activation, and atrial fibrillation drivers were defined as rotors (phase singularities) lasting more than 200ms. The sites exhibiting high rotor activity were defined as driving regions and targeted by catheter ablation, with the acute endpoint of AF termination. We assessed the relationship between global LGE burden and patients' clinical characteristics, electrophysiological characteristics, and acute procedural success. In a subset of 12 patients, CMR and BSM data were registered to assess the spatial relationship between LGE and AF drivers.Mean AF duration was 8+/-6 months. On CMR, the mean LGE burden on the left atrium was 22+/-5.9%. According to Utah classification, there were no class I, 16 class II, 21 class III, and 4 class IV. On BSM, the mean number of driving regions targeted by ablation was 4.3+/-1.7 per patient (range 2 to 8). AF could be terminated by ablation in 28/41 (68%) patients. LGE was positively related to AF duration  and to the number of driving regions . LGE did not relate to age  or gender . LGE burden and the number of driving regions were both inversely related to acute procedural success . In the subset of 12 patients with registered CMR and BSM data, visual analysis of rotor trajectories showed a clustering around LGE areas .Focal atrial fibrosis assessed by LGE CMR is associated to persistent AF duration and to the number of regions driving the arrhythmia, i.e. a surrogate for AF complexity. In patients undergoing catheter ablation targeting AF drivers, the extent of focal fibrosis is inversely related to acute procedural success. Futhermore, atrial fibrillation drivers are clustered along the borders of fibrotic areas.N/A.


MI) size when administered prior to reperfusion are required to prevent the onset of heart failure in ST‐segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI). Experimental animal studies have demonstrated that mineralocorticoid receptor antagonist (MRA) therapy administered prior to reperfusion can reduce MI size, and MRA therapy prevents adverse left ventricular (LV) remodeling in post‐MI patients with LV impairment. With these 2 benefits in mind, we hypothesize that initiating MRA therapy prior to PPCI, followed by 3 months of oral MRA therapy, will reduce MI size and prevent adverse LV remodeling in STEMI patients. The MINIMISE‐STEMI trial is a prospective, randomized, double‐blind, placebo‐controlled trial that will recruit 150 STEMI patients from four centers in the United Kingdom. Patients will be randomized to receive either an intravenous bolus of MRA therapy (potassium canrenoate 200 mg) or matching placebo prior to PPCI, followed by oral spironolactone 50 mg once daily or matching placebo for 3 months. A cardiac magnetic resonance imaging scan will be performed within 1 week of PPCI and repeated at 3 months to assess MI size and LV remodeling. Enzymatic MI size will be estimated by the 48‐hour area‐under‐the‐curve serum cardiac enzymes. The primary endpoint of the study will be MI size on the 3‐month cardiac magnetic resonance imaging scan. The MINIMISE STEMI trial will investigate whether early MRA therapy, initiated prior to reperfusion, can reduce MI size and prevent adverse post‐MI LV remodeling.Novel therapies capable of reducing myocardial infarct ( Coronary artery disease is one of the leading causes of death and disability worldwide,Although timely reperfusion is required to salvage viable myocardium in STEMI patients, the restoration of coronary blood flow in the infarct‐related artery has the potential in itself to induce cardiomyocyte death, a phenomenon that has been termed myocardial reperfusion injury and can contribute up to 50% of the final MI size.Aldosterone, a mineralocorticoid receptor agonist, is synthesised primarily in the adrenal gland and is part of the renin‐angiotensin‐aldosterone system. It is known to regulate a number of pathophysiological pathways important to post‐MI HF, including inhibition of nitric oxide activity,Experimental preclinical data have demonstrated that administering MRA therapy by a clinically relevant regimen, using either intravenous potassium canrenoate (a compatible metabolite of spironolactone) or eplerenone, after a sustained episode of myocardial ischemia and 5 minutes prior to reperfusion, protected the heart against myocardial reperfusion injury and reduced MI size by 40% to 50% in murine, rat and rabbit in vivo models of MI.Therefore, in this study we aim to combine the acute benefit of MRA therapy to reduce reperfusion injury and its benefit on preventing LV remodeling after 3 months of oral therapy. We hypothesize that early intravenous MRA therapy administered prior to reperfusion followed by 3 months of oral MRA therapy can reduce MI size and reduce adverse LV remodeling in STEMI patients.https://clinicaltrials.gov, NCT01882179) is a proof‐of‐concept randomized clinical trial designed to investigate whether MRA therapy initiated prior to reperfusion and continued for 3 months can reduce MI size and prevent adverse LV remodeling at 3 months in STEMI patients treated by PPCI. It is a prospective, randomized, double‐blind, placebo‐controlled clinical trial that will recruit 150 patients through 4 tertiary care hospitals in the United Kingdom. The study will be conducted in accordance with the Declaration of Helsinki and has been approved by the National Research Ethics Service. All patients will provide informed written consent.The MINIMISE‐STEMI trial (The main objective will be to investigate whether MRA therapy initiated prior to PPCI and continued for 3 months reduces MI size and prevents adverse LV remodeling in STEMI patients.+) <5.0 mmol/L and estimated glomerular filtration rate (eGFR) >30 mL/min/1.73m2) will be confirmed and patients will then be randomized to receive either MRA therapy or matching placebo. A detailed informed written consent will then be obtained on the ward following the PPCI procedure, within 24 hours after obtaining brief informed written consent, but before the patient is started on oral study medication. Blood tests will be taken to measure high‐sensitivity troponin T (hsTropT) and creatine kinase‐MB isoenzyme (CK‐MB) at the following time points pre‐PPCI and 6, 12, 24, and 48 hours post‐PPCI. In the first week following hospital admission, the patient will undergo a cardiovascular magnetic resonance imaging (MRI) scan  in a 1:1 manner to either MRA therapy or matching placebo. Randomization will be stratified by recruiting site. The patient, interventional cardiologist, caregivers, and data collector will be blinded to the treatment allocation. The study drug or placebo will be administered by the nonblinded research investigator.Eligible patients will be randomized via a Web‐based service MRA therapy will be stopped. Serum K+ will be checked at 2 and 4 weeks. Spironolactone will only be uptitrated to 50 mg after 2 weeks if the serum K+ is ≤5.0 mmol/L. If the serum K+ is 5.1 to 5.5 mmol/L, 25 mg spironolactone will be maintained, and if the K+ is >5.5 mmol/L, spironolactone will be discontinued.Patients randomized to + will be checked at 2 and 4 weeks.Patients randomized to control will receive an intravenous bolus of normal saline followed by placebo control tablets for the 3 months, after which the placebo will be stopped. Serum KThe study protocol will ensure optimal medical therapy for all study participants according to current practice guidelines.Each patient recruited into the MINIMISE‐STEMI trial will have 2 CMR scans, the first being performed in the week following hospital admission and the second performed at 3 months. Training in the CMR protocol will be provided to each recruiting site. All CMR scans will be analyzed by an independent MRI CoreLab at University College London.LVEF and indexed LV end‐systolic and end‐diastolic volumes and mass using short‐axis steady‐state free‐precession cine imaging.MI size, measured by the mass of LGE (10 minutes after administration of contrast) on CMR expressed as a percentage of LV mass.Area at risk (AAR), measured as the increase in T2 signal on‐T2 weighted images or T2 mapping, both of which have been validated against conventional measures of the AAR.Myocardial salvage index = AAR − MI size/AAR. The myocardial salvage index (using T2‐weighted CMR and LGE) has been demonstrated to predict prognosis post‐PPCI.The incidence and extent of microvascular obstruction (hypo‐enhancement on LGE 20 minutes after administration of contrast).The incidence and extent of intramyocardial hemorrhage (hypo‐enhancement on Siemens T2* mapping sequence).The primary endpoint of MINMISE‐STEMI trial will be MI size on the 3‐month CMR scan (measured as the mass of late gadolinium enhancement (LGE) and expressed as a percentage of the LV mass). The CMR parameters that will be determined for the first CMR scan:LVEF and indexed LV end systolic and diastolic volumes, wall thickness, and mass using short‐axissteady‐state free‐precession cine imaging.Final MI size, which represents the primary endpoint, measured by the mass of LGE and expressed as a percentage of the LV mass.The CMR parameters that will be determined for the second CMR scan, at 3 months:The CMR images will be analyzed by 2 experienced operators blinded to the treatment allocation and clinical outcome. Datasets will be reported in consensus, and advice from a third MRI operator will be sought in cases of disagreement .The primary endpoint of the MINIMISE‐STEMI study will be MI size quantified by LGE cardiac MRI performed at 3 months following hospital admission. The secondary endpoints are listed in Table 1, of 40.0 g, and a Group 2 mean, μ2, of 32.0 g), assuming that the common SD is 14.0 g infarct masst test with a 0.05 2‐sided significance level. However, we anticipate that about 10% of patients in the control group will have LVEF ≤40%, in which case they will receive the trial treatment as a matter of standard care. To allow for this dilution of the treatment effect, we have increased the sample size in each group to 62. If we further assume an attrition rate of approximately 15%, then 75 patients per group will be needed, for a total trial size of 150 patients.A sample size of 50 in each group will have 80% power to detect a difference in means of 8.0 g infarct mass as assessed by MRI . The Fisher exact test will be used to compare categorical variables. Continuous variables will be compared with a mixed‐effects model to account for repeated measures. Primary data analysis will be performed in the intention‐to‐treat population, regardless of the treatment that was actually received. The results of as‐treated analyses for primary and secondary endpoints will also be calculated. Time‐to‐event analyses , based on all available follow‐up data, will be performed with the use of Kaplan‐Meier estimates and be compared between groups with the use of the log‐rank test. A generalized linear model will be used to calculate risk ratios in the subgroup analyses and to test for interactions. After 75 patients have completed the trial, an interim analysis will be performed by the study statistician for safety reasons. The results will be evaluated by the data‐monitoring committee.University College London is the sponsor of the trial. Data will be collected by a paper case report form and entered onto the Web‐based electronic RedCap database. An independent data‐monitoring committee (IDMC) will be installed to monitor the progress of the study as well as any safety concerns. All expected or unexpected adverse events will be reviewed continuously by the investigators, the sponsor and the IDMC according to the sponsor's regulations. The MINIMISE‐STEMI trial is funded by the Rosetrees Trust and the National Institute for Health Research (NIHR) Clinical Research Network.Although the study has been open to recruitment since November 2013, recruitment has been slow, but it is expected to improve with the recent expansion to a fourth center. We currently have 24 patients enrolled in the study, and we anticipate to recruit a further 51 patients over the next 6 months (July 2015), when an interim analysis will be performed. We plan to complete recruitment in February 2016, with the last patient having the 3‐month CMR scan in May 2016 and the results of the study available in August 2016.The MINIMISE‐STEMI trial is designed to investigate whether MRA therapy using spironolactone initiated prior to reperfusion and continued for 3 months can reduce MI size and prevent adverse LV remodeling at 3 months in STEMI patients treated by PPCI, when compared with placebo control. The Eplerenone Post‐AMI Heart Failure Efficacy and Survival (EPHESUS) study demonstrated a 15% relative risk reduction in death at 16 months in AMI patients with LVEF <40% and HF signs administered oral eplerenone therapy (initiated 3–14 days post‐MI) when compared with matching placebo.Hayashi et alWhether early intravenous MRA therapy administered prior to reperfusion followed by 3 months of oral MRA therapy can reduce MI size and reduce adverse LV remodeling is not known and will be investigated in the MINIMISE‐STEMI trial.By administering the MRA therapy prior to reperfusion, we hope to target myocardial reperfusion injury and obtain additional benefit in terms of MI size reduction, which will hopefully add to the known beneficial effects of oral MRA therapy in terms of preventing post‐MI adverse LV remodeling.Key study participants and committee membersClick here for additional data file.


The relationship between pulmonary vein (PV) anatomy and successful catheter ablation of atrial fibrillation (AF) is poorly understoodFirst-pass contrast enhanced PV magnetic resonance angiography was performed in 71 consecutive patients prior to PV isolation. PV diameter and cross-sectional area (CSA) were measured prior to PV isolation. Any symptomatic or asymptomatic AF >10s was considered a recurrence. Early recurrence was defined as recurrent AF ≤30 days after PV isolation, while late recurrence of AF was defined as recurrent AF >30 days after.th percentile had trend toward more early recurrent AF . Study subjects with one or more PV CSA in the top 10th percentile had more late recurrent AF  and a trend toward more early recurrent AF . With multivariate analysis, PV size was not associated with early recurrent AF, but late recurrent AF was associated with one or more large PV, increased left atrial size, and non-paroxysmal AF. Study subjects with all three of these risk factors had a 100 % rate of late recurrent AF at 1 year, while those with none had a 7 % rate of late recurrent AF.At 1 year, 57 % had any recurrence of AF while 41 % had late recurrence of AF. Study subjects with one or more PV diameter in the top 10Larger PV size is independently associated with more late recurrent AF after PV isolation. Determination of PV size prior to PV isolation may predict procedural success. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia . The recWe hypothesized that patients with large PV would be at higher risk for electrical reconnection and thus more recurrent AF after PV isolation. We evaluated this hypothesis in a consecutive series of 71 patients who underwent PV magnetic resonance angiography (MRA) prior to PV isolation.The study cohort was comprised of a consecutive series of 71 patients who underwent cardiovascular magnetic resonance (CMR) prior to PV isolation for the treatment of AF. The clinical characteristics of the study cohort are summarized in Table CMR was performed using a 1.5 T whole-body MR system  with a five-element cardiac synergy coil for radiofrequency signal reception.First pass breath-hold 3D contrast enhanced MRA of the PV was obtained after manual bolus administration of 0.2 mmol/kg gadopentetate dimeglumine , immediately followed by a saline flush. Data acquisition began after a delay determined by a small timing bolus given prior to contrast enhanced MRA. A spoiled end-expiratory breath-hold 3D gradient echo sequence with the following parameters was used: repetition time 3.6 ms, echo time 1.1 ms, flip angle 30 degrees, 50 slices, slice thickness 4 mm interpolated to 2 mm, field of view 480 mm, matrix 272 × 512, imaging time 22 s. The 3D volume was centered on the left atrium and included all PV. Images were prospectively acquired in the axial plane. Commercially available system software  was used to generate multiplanar reformations.Steady-state free-precession breath-hold gradient echo ECG-gated cine CMR was performed in the 4-chamber and contiguous short axis orientations during a series of end-tidal breath-holds. Short axis images were acquired from the left ventricular base to the apex with 10 mm slices and no gap. The following parameters were used: repetition time 3.0 ms, echo time 1.5 ms, flip angle 60 °, field of view 480 mm, matrix 208 × 256.All measurements were made by an observer blinded to the clinical treatment data using commercially available system software . The maximum left atrial dimension was measured in the 4-chamber orientation. Left ventricular volumes, mass and ejection fraction were determined using Simpson’s rule . The PV th percentile of all PV was defined as having a large diameter. Similarly, any PV with a CSA in the top 10th percentile was defined as having a large CSA. A separate analysis was performed for each measure of PV size.Any PV with a diameter in the top 10The electrophysiology procedure was performed using a femoral venous approach. A decapolar catheter was positioned in the coronary sinus and a second catheter was placed in the right atrium. Left atrial access was obtained by two transseptal punctures. Transesophageal or intracardiac echocardiography was used to identify PV anatomy and velocities before and after ablation, to identify catheter position with reference to the vein ostia, to determine the presence or absence of pericardial effusion, and in some cases to guide transseptal puncture. Following transseptal puncture, patients received intravenous heparin to maintain a serum activated clotting time >250 s.Three-dimensional electroanatomic mapping of the left atrium and PV was performed using a non-irrigated 4 or 8 mm tip NaviStar™ catheter (Biosense Webster) and CARTO™ (Biosense Webster) and/or EnSite NavX™  recording systems. Electrograms were recorded during sinus rhythm, coronary sinus pacing, or AF at the ostia of the PV with a 10–14 pole circumferential catheter with distal ring configuration (Biosense Webster or Bard). Radiofrequency ablation was performed outside the PV ostium near sites with the earliest PV electrograms. Ablation was performed for 20–60 s with a target temperature of 52 °C. Temperature was considered adequate if it reached 45 °C. The process was repeated until complete bi-directional electrical PV isolation was achieved, defined by both entrance block as demonstrated by loss of PV potentials, and exit block demonstrated by failure to capture the left atrium during sinus rhythm by pacing (at 10 mA and 2 ms pulse width) each of the bipolar pairs of electrodes of the circumferential catheter positioned at the entrance of the PV. All PV were routinely isolated for all patients.After PV isolation, induction of AF was attempted by burst pacing from the right atrium and coronary sinus before and after administration of isoproterenol. Isolation of the PV was reassessed and if reconnection was observed the vein was re-isolated. Left atrial ablation lines  were performed in 16 (23 %) patients with inducible sustained left atrial tachycardia. A right atrial isthmus line  was performed in 17 (24 %) patients with a history of or inducible right atrial isthmus dependent flutter.Patients were treated with warfarin to achieve an international normalized ratio of 2.0 to 3.0 for at least 6 months after PV isolation, as well as acetylsalicylic acid (325 mg/day) for at least 1 month. Antiarrhythmic drugs were continued post procedure for patients with a history of persistent or permanent AF, and were reinitiated in patients with early (<30 days) recurrences of AF. Antiarrhythmic drugs were used in 29 (41 %) patients post procedure, including 12 (29 %) free of AF at last follow-up.Evaluation of symptomatic or asymptomatic AF was performed using both a 2 week transtelephonic event recorder and 24 h Holter monitor at 1, 3, 6, and 12 months. Additional monitoring was done for patients with symptoms. Recurrent AF was deemed present if an asymptomatic or symptomatic atrial tachyarrhythmia consistent with AF was documented to last >10 s. Early recurrent AF was defined as any recurrent AF during the first 30 days. Late recurrent AF was defined as recurrent AF after 30 days. The median duration of follow-up was 442 days.Continuous values are reported as the mean ± standard deviation. Categorical values are reported as counts and percentages. The occurrence of recurrent AF was estimated using the product-limit (Kaplan-Meier) method. The relationship between PV size and recurrent AF was assessed using the product-limit method and the log rank test. The relationship of PV size and clinical variables with recurrent AF was assessed using proportional hazards regression. The proportional hazards assumption was confirmed for all variables by examining log-log survival curves. Multivariate analysis was performed using proportional hazards regression with backward selection of variables. Any variable with a p-value of ≤0.1 was eligible for inclusion and retention in the model. Hazard ratios (HR) are reported as the estimate with the 95 % confidence interval (CI). A p-value of <0.05 was used for determination of statistical significance. All statistical analysis was performed using SAS for Windows .The mean duration of the electrophysiological procedure was 257 ± 63 min. The mean number of ablations performed was 73 ± 25 with a mean total ablation time of 53 ± 23 min. There was no relationship between the procedure time, total number of ablations or total ablation time with any measure of PV size or with the presence of one or more large PV by any measurement criteria .At 1 year of follow-up, 57 % had any recurrent AF and 41 % had late recurrence of AF  patients had one or more PV with a large diameter and 23 (32 %) had one or more PV with a large CSA. Multiple large PV were present in 2 patients with large diameter PV and 3 patients with large CSA PV. The distribution of large PV is shown in Table Size measurements for all PV are shown in Table The relationship between recurrent AF and the presence of one or more large CSA PV was further investigated with multivariate proportional hazards regression Table . With siWe further evaluated the late recurrence of AF by stratification of study subjects by the presence of one or more large PV by CSA criteria Fig. , which sth percentile had recurrent AF at 1 year while only 7 % of study subjects without these risk factors had late recurrent AF at 1 year.In this prospective study of 71 consecutive patients undergoing CMR prior to PV isolation, we found that PV size, left atrial size, and paroxysmal AF are significantly and independently related to late recurrent AF after PV isolation. As PV isolation for the treatment of AF becomes more common, the appropriate selection of patients for these procedures becomes more important. In our study, 100 % of study subjects with non-paroxysmal AF, increased left atrial size, and one or more PV with a CSA in the top 10The PV have a critical role in the pathophysiology of AF. The PV and left atrium are both derived from the primitive common PV  and therth percentile for CSA were at increased risk of late recurrent AF.Recurrent AF after these procedures has generally been attributed to recovery of electrical function after the procedure., 9 LargeParoxysmal AF has been previously described as predicting better outcome after PV isolation compared to persistent or permanent AF. –19 We alLeft atrial size has been previously reported to predict increased rates of recurrent AF, independent of other predictors, , 20, 21 Left atrial fibrosis has also been described as a predictor of recurrent AF after PV isolation . We did We found no other significant relationships of late recurrent AF with any other clinical or anatomic factors. Although advancing age , diabeteWe also examined early recurrence of AF in our dataset and found that male gender, paroxysmal AF, LV cavity size, left atrial size and the presence of one or more large PV were all associated with early recurrence of AF. With multivariate analysis, male gender, paroxysmal AF and LV cavity size remained significantly associated with early recurrence of AF. Male gender  and leftWe rigorously screened our study cohort for symptomatic or asymptomatic AF using both a 2 week transtelephonic event recorder and 24 h Holter monitor at each follow-up interval as well as additional monitoring for patients with symptoms. All patients with any recurrent AF were deemed a treatment failure even if sinus rhythm was later restored. As a result, our rate of late recurrent AF of 41 % at 1 year is higher than that reported by other investigators .Among patients referred for their initial PV isolation, the presence of one or more large PV CSA, non-paroxysmal AF, and increased left atrial size were independent predictors of late recurrent AF after PV isolation. Stratification by the number of these factors present identified three risk groups. Patients with all three risk factors had a very high rate of recurrent AF. Patients with no risk factors had a very low rate of recurrent AF. The remaining patients had an intermediate rate of recurrent AF. These results suggest that determination of PV size prior to PV isolation may predict procedural success and identify patients for whom the procedure is unlikely to result in long-term success.


Takotsubo cardiomyopathy (TC) is characterized by a transient decrease in ejection fraction and a reversible left ventricular dysfunction. The pathophysiology of TC is not completely understood. Heterogeneous and multifactorial mechanisms are involved: drugs, emotional and physical stress, genetic and hormonal factors.A 17 year-old male with metastatic pancreatic adenocarcinoma, under chemotherapy containing 5-fluorouracil, presented severe left ventricular dysfunction requiring mechanical ventilation and inotropes administration. He completely recovered in 2 weeks.To our knowledge this is the first report of transient form of ventricular dysfunction, mimicking TC, in an adolescent. We believe that children and adolescents receiving 5-fluorouracil should be closely monitored and referred for investigation if they develop cardiac symptoms.The online version of this article (doi:10.1186/s12887-016-0628-4) contains supplementary material, which is available to authorized users. Takotsubo cardiomyopathy is a reversible cardiomyopathy characterized by a transient decrease in ejection fraction and a reversible left ventricular dysfunction. The pathophysiology of TC is not completely understood. Heterogeneous and multifactorial mechanisms are involved: drugs, emotional and physical stress, genetic and hormonal factors. TC is most often seen in elderly women and has never been reported in an adolescent .2, followed by leucovorin, 400 mg/ m2, irinotecan, 180 mg/ m2 and 5-fluorouracil (5-FU) at a dose of 400 mg/m2 by intravenous bolus, followed by a continuous intravenous infusion of 2400 mg/m2 over a 46-hour period. Approximately 4 h after the start of the first 5-FU infusion, the patient experienced vomiting and chest pain as well as an altered level of consciousness with extreme agitation. Progressive diuresis contraction was also recorded. Vital signs were: blood pressure 112/87 mmHg, heart rate 134/min and regular. Brain and thorax CT scans and abdominal x-ray were normal. Monitoring of vital signs revealed a progressive decrease of blood pressure down to 90/50 mmHg. Echocardiography showed severe and diffuse LV hypokinesis with an ejection fraction of 20 %. Moderate right ventricular hypokinesis and a 20 × 16 mm thrombus in the right atrium were also revealed , also known as apical ballooning syndrome, is a quite new clinical entity characterized by a transient decrease in ejection fraction and a reversible LV dysfunction consisting of dyskinesia involving the apical or midventricular segments. TC is most often seen in elderly women. In a review of studies from 2000 to 2012, Bossone et al reported that the age of patients affected by TC ranged from 59 to 73 years . FamiliaSeveral reports have discussed drugs that may cause TC , 7. AmonAccording to the reported cases, TC is often seen in elderly women who frequently have histories of smoking, alcohol abuse, anxiety states, and hyperlipidemia. Our patient however, was an adolescent, with no previous history of cardiac dysfunction or other reported risk factors. He was under treatment for pancreatic adenocarcinoma with liver metastases and, 4 h after the start of 5-FU infusion, he developed chest pain and an altered level of consciousness, which are typical findings associated with TC. Echocardiography showed severe and diffuse LV hypokinesis with an increased level of cardiac enzyme B-Type natriuretic peptide, troponin and myoglobin, leading us to hypothesize TC. To our knowledge this is the first reported case of 5-FU- induced transient form of ventricular dysfunction, mimicking TC, in an adolescent. This is probably due to the fact that the drugs recognized as possible triggers of TC are not currently used in pediatric and young populations affected by cancer .The chemotherapeutic agent 5-FU, by inhibiting thymidylate synthase in malignant cells, disrupts DNA synthesis and promotes cell death. It is currently used as adjuvant chemotherapy for colorectal cancer and frequently for the treatment of pancreatic, breast, bladder, gastric, esophageal and prostate cancer . These nAlthough TC has only been reported in adults, children and adolescents with cardiac symptoms during chemotherapy with 5-fluorouracil should be closely monitored and referred for further investigations if there is suspicion of this condition. Prompt acute clinical assessment coupled with ECG recordings and cardiac enzyme analysis should be performed if cardiotoxicity is suspected. Further studies are necessary to be able to assess the real incidence of TC in the pediatric population.5-FU, 5-fluoruracil; LV, left ventricular; TC, takotsubo cardiomyopathy


Functional mitral regurgitation may have different haemodynamic consequences, clinical implications and treatment options, such as surgical or percutaneous interventions or implanting a pacemaker. Here we present two cases with haemodynamically significant intermittent functional mitral regurgitation as the underlying mechanism of heart failure. The cases underline the importance of a high index of suspicion in patients with intermittent heart failure, and a careful analysis of echocardiographic images with simultaneous ECG, in order to delineate systolic and diastolic mitral regurgitation. Heart failure (HF) in patients with normal left ventricular ejection fraction accounts for half of the diagnoses of HF. Careful echocardiographic analysis with simultaneous ECG in two patients developing acute heart failure allowed identification of an unusual cause of HF with normal left ventricular ejection fraction (LVEF), but related to sudden reversible functional mitral regurgitation in the absence of significant coronary artery stenosis.A 54-year-old female was admitted to hospital with acute pulmonary oedema. Her ECG showed sinus tachycardia with left bundle branch block (LBBB) morphology, with a rate of 125 beats per min (bpm). Her symptoms improved following spontaneous conversion to sinus rhythm without LBBB.2 and 1.3 cm, respectively. The mitral annular dimension was 4.2 cm.Two-dimensional echocardiography revealed concentric left ventricular (LV) hypertrophy with normal systolic function (LVEF 70%), with mild rheumatic mitral regurgitation (MR), mild left atrial dilatation (4.3 cm) and elevated pulmonary artery systolic pressure (50 mmHg). The tenting area of the mitral leaflets and the tenting length was measured as 3.9 cmThe results of her laboratory examination were normal. Her medical history was unremarkable for cardiovascular disease and she was not taking any anti-arrhythmia drugs. Since her symptoms occurred again the following day, the echocardiographic examination was repeated. In the second study, the rhythm was sinus tachycardia with LBBB morphology. The QRS duration was 150 ms.2 with a regurgitant volume of 67 ml. The tenting area of the mitral leaflets and the tenting length were 7.8 cm2 and 1.8 cm, respectively. The mitral annular dimension was 4.8 cm.Transoesophageal echocardiography (TEE) revealed marked asynchronous contraction and dilatation of the left ventricle and atrium (5.1 cm). The left atrium was seen as being larger in this second assessment (5.1 cm), with severe MR . The effAfter spontaneous narrowing of the QRS duration to 60 ms, the third echocardiography showed mild MR with improved pulmonary pressure . IschaemBecause of the severe symptoms, which were resistant to medical therapy, we decided to perform mitral valve repair surgery. Mitral valvuloplasty with a rigid annuloplasty ring  was performed. Within two years following the procedure, the patient had no symptoms of heart failure despite having paroxysmal LBBB attacks.A 56-year-old female had complained of exertional dyspnoea and gradual intolerance during exercise for the previous three months. Transthoracic echocardiography (TTE), which was performed in another hospital, had revealed moderate-to-severe mitral regurgitation and therefore she was referred to have surgery for mitral valve replacement.Her medical history was unremarkable for cardiovascular disease and she was not taking any anti-arrhythmia drugs. Initially, ECG revealed sinus rhythm with a heart rate of 66 bpm.max = 1.2 m/s, V–A gradient of 6 mmHg) that regularly followed blocked P waves  block, and colour Doppler echocardiography revealed moderate early and mid-diastolic mitral regurgitation jets  is classified as either primary  or functional.Ischaemia is a well-known cause of functional MR.5et al. reported severe mitral regurgitation with symptoms of heart failure that was induced by methylergonovine injection. Possible underlying mechanisms were epicardial focal spasm, diffuse epicardial vasoconstriction or microvascular dysfunction.Avierinos Rhythm and conduction disturbances are also common causes of mitral regurgitation. Electromechanical asynchrony can alter the left ventricular contraction pattern. Left bundle branch block (as in our first case) is an example of ventricular asynchrony related to functional mitral regurgitation.7Functional mitral regurgitation in patients with left bundle block has multiple components, including asynchrony of the papillary muscles due to delay in ventricular conduction, which causes a delay in the contraction of the papillary muscles.Long-term right ventricular (RV) apical pacing can also cause MR. It has been shown in canine models that RV pacing can increase mitral and tricuspid valve incompetence.et al. demonstrated that RVA pacing may immediately induce severe MR and acute cardiac failure, even in patients with preserved LV contraction.Left ventricular dyssynchrony can be considered as a cause of MR after long-term RV apical pacing. There are a few reported cases of acute severe MR as an immediate perioperative complication of pacemaker insertion, leading to acute haemodynamic deterioration. Rita Diastolic mitral regurgitation (DMR) is a common phenomenon seen in patients with AV blocks, hypertrophic cardiomyopathy, advanced left ventricular systolic dysfunction, aortic valve disease, and in the presence of atrial fibrillation with long cardiac cycles. The haemodynamic mechanism leading to DMR is due to a positive ventricular-to-atrial (V–A) pressure gradient occurring during diastole.14These two cases illustrate different mechanisms of mitral regurgitation, which may have different haemodynamic consequences and clinical implications. The cases underline the importance of a high index of suspicion in patients with intermittent heart failure, and a careful analysis of echocardiographic images with simultaneous ECG, in order to delineate systolic and diastolic MR.


Atrial fibrillation is the most common arrhythmia in United States, and is associated with atrial fibrosis. Although the cause of atrial fibrosis development is not understood, its etiology is related to cardiac dysfunction, mitral regurgitation (MR), and coronary artery disease. This study focuses on determining the acute effects of myocardial infarction (MI) on left atrial (LA) function. Our hypothesis is that MI may result in changes in left ventricular relaxation, MR, and LA pressure and volume overload, leading to changes in LA geometry and mechanics, which will result in later atrial fibrosis. We studied the changes in LA size, ejection fraction, and the relative contributions of passive and active emptying, comparing controls with post-MI animals.3 spatial resolution (no gaps), and 25 frames, breath-holding and retrospective ECG-gating.Eleven Yorkshire pigs (average weight 37 ± 7 kg) were studied, including 5 control animals, and 6 pigs imaged one to two weeks after a transmural MI. The MI was induced by percutaneous balloon occlusion of left coronary artery (90 min) followed by reperfusion. All animals were imaged on a 1.5T Siemens scanner . A stack of short-axis cine images covering the left atrium were obtained with balanced SSFP, with a 1.3 x 1.3 x 3 mmAll image processing was performed in Matlab (v 2014). To measure LA volume through the cardiac cycle, the cine images were segmented using thresholding, and regions of interest excluding the pulmonary veins, in each slice and each time frame. Figure Table QA Truong et al. Intl Journal of Cardiology, 2011.Using quantitative analysis of high resolution SSFP MRI we demonstrate increased LA volumes in swine post-MI. These findings are similar to those reported in patient studies of acute MI, where LA volumes are increased relative to controls (1). Future work will relate these volume changes to atrial fibrosis development.We gratefully acknowledge funding from NHLBI R01HL113352.


Quantification of myocardial T1 values is a promising tool that may be used to quantify myocardial fibrosis. The purpose of our study is to establish a preliminary reference value of normal left ventricular (LV) myocardium in children and young adults using non-contrast T1 mapping.The HIPAA compliant prospective study was IRB approved. Sixteen patients  underwent cardiac magnetic resonance (CMR) (1.5-T) including non-contrast short axis T1 mapping (modified Look-Locker [MOLLI] sequence). Twelve patients with no intrinsic myocardial abnormality based on clinical history, standard biomarkers and echocardiographic criteria were compared with 3 patients having cardiac dysfunction and 1 patient with hypertrophic cardiomyopathy (HCM). Short axis images were manually contoured to outline the epicardium and endocardium using AHA 16-segment model yielding 192 normal myocardial segments, 48 segments in patients with cardiac dysfunction, and 16 segments in a patient with HCM. Patient groups were compared using one-way analysis of co-variance (ANOVA). Chi-squared test was performed to compare appropriateness of discrete data. Receiver operating characteristic (ROC) curve was used to obtain a cut-off value of T1 relaxation time. Statistical significance was defined as p < 0.05.Myocardial T1 values in the normals (982.1 ± 30.0 ms) were significantly different (p < 0.001) when compared to patients with cardiac dysfunction (1021.0 ± 34.8 ms) and hypertrophic cardiomyopathy (1039.7 ± 20.8 ms). Non-contrast myocardial T1 cutoff of 1005 ms conceded a sensitivity of 80% and specificity of 83% when compared to patients with cardiomyopathy (p < 0.001).The normal non-contrast T1 values of LV myocardium in children and young adults obtained can be used as a baseline for comparison to patients with underlying myocardial abnormalities. Enrollment is underway to validate our results in a larger cohort.None.