To compare the prognostic value of cardiac valve plane displacement (CVPD) on various locations in cardiac light chain (AL) amyloidosis.Consecutive patients with biopsy-proven cardiac involvement in AL amyloidosis who had undergone cardiovascular magnetic resonance (CMR) between 2005 and 2014 in our institution, were retrospectively identified and data analyzed. The primary combined endpoint was all-cause mortality or heart transplantation. Systolic CVPD were obtained from standard cine bSSFP in 2-, 3- and 4-chamber views at anterior aortic plane systolic excursion (AAPSE); anterior, anterolateral, inferolateral, inferior, inferoseptal mitral (MAPSE); and lateral tricuspid (TAPSE) annular segments.n = 44) and transplant-free survivors were found only for AAPSE  vs. 8.8 mm ; p = 0.02) and MAPSEanterolateral  vs. 10.5 mm ; p = 0.03). AAPSE  provided the best predictive value for transplant-free survival compared to all other valvular plane locations. A high-risk cutoff (AAPSE ≤ 7.6 mm) was calculated by ROC analysis to predict all-cause death or heart transplantation within 6 months from index examination . AAPSE added incremental prognostic power to an imaging prediction model of late gadolinium enhancement and global longitudinal strain (GLS)  as well as to a clinical model including Karnofsky index and NT-proBNP .We identified 68 patients . Median follow-up period was 1.2 years . Significant differences in CVPD between patients who reached a primary endpoint  and provide incremental prognostic value to LGE and strain measurements. The early detection of myocardial protein infiltration is crucial to patient care in patients with suspected cardiac amyloidosis in systemic light chain amyloidosis (AL), as cardiac impairment determines overall prognosis and is present in up to 90% of patients during the course of the disease –4. The mLongitudinal systolic deformation of the left ventricle (LV) is known to be strongly associated with survival in AL amyloidosis –8. AtrioThe purpose of the present study was a head-to-head comparison of the prognostic value of cardiovascular magnetic resonance (CMR) measurement locations for cardiac valve plane displacement (CVPD) in patients with AL amyloidosis.We identified patients with cardiac biopsy-secured systemic AL amyloidosis who had undergone a CMR between February 2005 and October 2014 at our institution for a retrospective single-center post-hoc analysis. Patient selection is demonstrated in a flow chart Fig. . The mea2, repetition time/echo time (TR/TE) = 2.8/1.4 ms, acquired voxel size = 2.2 × 2.2 × 8 mm3, flip angle (FA) = 60°, reconstructed voxel size = 1.3 × 1.2 × 8 mm3. Data were analyzed by a single examiner blinded to the patients’ clinical status. Routine analysis was performed on a commercially available workstation  Version 7.0.1, Philips Healthcare, Best, The Netherlands) with a semi-automatic software for volumetric analysis. Ventricular volumes, ejection fraction and LV myocardial mass were acquired in short axis stacks by manually tracing epi- and endocardial borders, excluding papillary muscles from the myocardium. Relative LGE mass was measured using a 5-standard-deviation (SD) threshold in reference to visually unenhanced myocardium . Regional longitudinal strains are presented for basal , midventricular  and apical slices .All CMR examinations were performed on a 1.5 Tesla scanner  equipped with a cardiac phased array 32-channel receiver coil. Cine images were obtained using a breath-hold segmented-k-space balanced fast-field echo sequence (bSSFP) employing retrospective electrocardiogram (ECG)- or pulse oximetric gating with 35 phases per cardiac cycle. Typical CMR imaging parameters were: field-of-view (FOV) = 350 × 350 mmium Fig.  16]. LG. LG2, reRegional systolic valve plane excursion was assessed at seven locations on anterior aortic plane systolic excursion (AAPSE), anterior, anterolateral, inferolateral, inferior and anterolateral mitral (MAPSE), and lateral tricuspid annulus (TAPSE) derived from cine bSSFP images in 2-, 3-, and 4-chamber views as previously described . CVPD waBlood samples were drawn up to 14 days before the date of CMR examination. NT-proBNP  and cTNT (cardiac troponin T) were obtained from a commercially available fully automated analyzer based on a sandwich immunoassay . Glomerular filtration rate was estimated by the “Modified Diet in Renal Diseases” (MDRD) formula.Primary combined endpoint was all-cause mortality or heart transplantation. Follow-up was obtained by review of patient’s electronic records or telephone interview with the patient or relative.p ≥ 0.05) were expressed as mean ± standard deviation. Group differences for continuous variables were tested using the independent t-test, and differences between nominal variables were assessed using the Fisher exact test. Continuous variables without normal distribution were stated as median and interquartile range (IQR), group differences were tested using the nonparametric Mann-Whitney U test. Kaplan-Meier curves were used to estimate the distribution of survival as a function of the follow-up duration. Optimal cut-off values were defined by Receiver operating characteristics (ROC) and Youden’s J statistic. The association of clinical, imaging and serological parameters with outcome was evaluated by uni- and multivariate Cox proportional-hazards regression models. Differences were considered statistically significant at p < 0.05.Data were analyzed using MedCalc, version 15.11.4 . Continuous and normal distributed variables  and Karnofsky index  were both accentuated in patients with primary endpoint. Regarding established serum biomarkers, only NT-proBNP showed significant differences between transplant-free survivors and patients with primary endpoint  vs 3243 pg/mL ; p = 0.01). Among all annular locations, only AAPSE  vs 6.1 mm ; p = 0.02) and MAPSEanterolateral  vs 7.3 mm ; p = 0.03) were significantly reduced in patients who died or were heart transplanted during the follow up period.Sixty-eight AL patients were included with a median follow up of 1.2 years , of whom 44 (64.7%) did not survive this period. Patients’ characteristics are demonstrated in Table 2 = 15.6; p = 0.0002) was found the best predictor of transplant-free survival compared to all other valvular plane locations as well as relative/ qualitative LGE, GLS or regional longitudinal strain in univariate Cox-regression analysis  was also found beneficial for predicting a combined endpoint of cardiac death, heart transplantation, and hospitalization compared to other established parameters .AAPSE (χp < 0.0001). The Kaplan-Meier survival curve is demonstrated in Fig. p ≤ 0.0001). Median survival of patients with AAPSE ≤7.6 mm was 0.5 years  compared to 3.9 years .An optimized cut-off value for AAPSE of ≤7.6 mm was calculated to predict whether patients would reach a primary endpoint within 6 months from index examination  and an imaging prediction model  .To further evaluate the incremental predictive power of AAPSE for transplant-free survival, a sequential Cox-regression was performed for a clinical  The data were obtained retrospectively and have to be confirmed in later, prospective samples. 2) The study was performed at a single-center and was restricted to patients with AL amyloidosis, which limits its generalizability. 3) The study cohort might be selection biased excluding patients unable to perform a CMR examination with rest dyspnea, severe arrhythmias, or claustrophobia.The predictive value of cardiac valve plane excursion varies between different annular locations. The Anterior Aortic Plane Systolic Excursion (AAPSE) appears to best predict all-cause mortality or heart transplantation in systemic AL amyloidosis with incremental prognostic value to established clinical, biochemical, and imaging prognosticators.


The presence of myocardial fibrosis in hypertrophic cardiomyopathy (HCM) is associated with a wide range of adverse outcomes including ventricular arrhythmia and sudden death in adults. Its presence suggests an adverse prognosis and may provide important therapeutic guidance. Native T1 can be an alternative to routinely used late gadolinium enhancement and has a potential to provide a non-contrast alternative in children.Our cohort population consisted of 21 patients  with hypertrophic cardiomyopathy undergoing routine clinical cardiac magnetic resonance (CMR). The diagnosis of HCM was based on the demonstration of a non-dilated hypertrophic left ventricle (LV) in the absence of increased LV stress or another cardiac or systemic disease that could result in a similar magnitude of hypertrophy. Twelve subjects  with low pre-test likelihood of cardiomyopathy, without any known cardiovascular disease, congenital or acquired by history, echocardiography, or CMR served as controls. In all subjects, breath hold, ECG triggered, 2D MOLLI TrueFISP data was acquired in short axis locations at base, mid-chamber, and apex. Native (non-contrast) myocardial T1 maps were calculated a T1 was quantified based in the 16-segment AHA model.Global native T1 (averaged over the entire LV) in patients with HCM was significantly increased compared to controls . Regional analysis demonstrated significantly elevated  native T1 in all 16 AHA segments. A T1 of > 990 msec yielded a sensitivity of 90% and specificity of 90% to identify patients with HCM (p < 0.05). There was a modest but significant correlation between native T1 and indexed LV mass . No correlation was identified between native T1 and heart rate, LV ejection fraction, indexed end-diastolic, and end-systolic volume . There was no significant difference in T1 values between HCM patients without and with late gadolinium enhancement (p = 0.07).Global and segmental native T1 values were elevated in patients with HCM, but did not correlate with parameters of LV structure and function. Native T1 of LV myocardium in children and young adults can be used as a non-invasive tool to identify patients with HCM with a high sensitivity and specificity. Further work should determine whether T1 mapping can guide cardiac risk stratification for children and young adults with HCM.


Some infants with congenital heart disease are at risk of in-hospital cardiac arrest. To better foresee cardiac arrest in infants with congenital heart disease, it might be useful to continuously assess end-organ perfusion. Near-infrared spectroscopy is a non-invasive method to continuously assess multisite regional tissue oxygen saturation.We report on two infants with duct-dependent congenital heart disease who demonstrated a gradual change in cerebral and/or renal tissue oxygen saturation before cardiopulmonary resuscitation was required. In both cases, other clinical parameters such as heart rate, arterial oxygen saturation and blood pressure did not indicate that deterioration was imminent.These two cases demonstrate that near-infrared spectroscopy might contribute to detecting a deteriorating clinical condition and might therefore be helpful in averting cardiopulmonary collapse and need for resuscitation in infants with congenital heart disease. Some infants with congenital heart disease (CHD) are at risk of cardiac arrest during hospitalization . In-hosp2) [2 was also assessed preoperatively in some studies [Monitoring end-organ perfusion might help recognizing clinical deterioration at an early stage. Near-infrared spectroscopy (NIRS) is a non-invasive clinical tool to continuously assess multisite regional tissue oxygen saturation (rSO2) . It is b2) . In infa2) –14. Most2) –10, but  studies –14. To oWe discuss two cases in which continuous monitoring of multisite tissue oxygen saturation using NIRS indicated a deteriorating clinical condition which eventually led to cardiac arrest.2 using INVOS 5100c near-infrared spectrometers  in combination with neonatal sensors (Somanetics Corporation). Nurses were not instructed to act on certain rSO2 values, as they were not measured for clinical purposes.Both cases in this report were part of a prospective observational cohort study (registration number NTR5233), which was conducted between May 2014 and August 2016. Parental informed consent was obtained in both cases. We measured cerebral and renal rSO2O with a maximum of 40% O2 and infusion with prostaglandin E1 (0.025 ug/kg/min) to maintain pulmonary circulation. Prenatal diagnosis and ductal patency were confirmed by the pediatric cardiologist. The patient appeared to be hemodynamically stable with transcutaneous oxygen saturations (SpO2) between 70% and 90% and mean arterial blood pressures between 46 and 73 mmHg. As the patient was clinically stable, further hemodynamic parameters were not available for this case.A boy diagnosed prenatally with pulmonary atresia with an intact ventricular septum was born at our hospital at a gestational age of 37.3 weeks. After birth, the patient was admitted to the neonatal intensive care unit (NICU) with continuous positive airway pressure (CPAP) at seven cmHFour hours after birth the boy developed three apneas. The third apnea was followed by loss of cardiac output. Cardiopulmonary resuscitation was initiated immediately according to protocol. Cardiac output and heart rate, however, remained insufficient and the boy died 6 h after birth.Autopsy confirmed the diagnosis of a pulmonary atresia with a hypoplastic right ventricle and an intact ventricular septum. Furthermore, autopsy revealed a single coronary ostium, multiple ventricular-coronary fistulas and a right ventricle dependent coronary blood flow with bridging of a branch of the right coronary artery. There were signs of recent myocardial ischemia, such as loss of cardiomyocytes. In addition, there was a left-sided open ductus arteriosus between the brachiocephalic trunk and the pulmonary artery. Based on autopsy findings, the most likely cause of death was considered to be massive myocardial ischemia which is not uncommon for this type of anatomy and physiology. Other causes such as a primary intraventricular hemorrhage or infarction cannot be ruled out completely since there was no permission for cerebral autopsy.2 were relatively low (around 40%) and decreased rapidly approximately 40 min before cardiopulmonary resuscitation was necessary  to approximately 20%. We cannot fully explain why cerebral rSO2 decreased before renal rSO2 and SpO2.Baseline cerebral and renal rSOary Fig. . This ra2O with a maximum of 40% O2 due to respiratory distress/delayed transition. Initially, she had a wide-open ductus arteriosus. Eighteen hours after birth her clinical condition deteriorated with signs of a duct-dependent systemic circulation. Therefore, prostaglandin E1 infusion was administered (0.025 ug/kg/min) to maintain ductal patency. During the first days after birth there was a fragile balance between pulmonary and systemic blood flow.A girl diagnosed prenatally with double outlet right ventricle, transposed great arteries, a ventricular septal defect and a hypoplastic aortic arch was born prematurely at our hospital at a gestational age of 34.9 weeks. She was admitted to the NICU with CPAP 10cmH2 was 4.8 kPa, hemoglobin was 8.0 mmol/l and lactate was 1.5 mmol/l. At that time, arterial blood pressure was 70/30 mmHg and she had normal diuresis. One hour later, she suddenly developed bradycardia followed by loss of cardiac output. Cardiopulmonary resuscitation was initiated immediately according to protocol. Infusion with prostaglandin E1 was transferred from a peripheral venous site to a central line and was increased in dosage. An echocardiogram suggested an open ductus arteriosus, revealed a poor contractility and an inadequate cardiac output. After 40 min of cardiopulmonary resuscitation, the sternum was re-opened. The heart, however, was almost non-contractile and the girl died 7 days after birth.At the sixth day after birth, she underwent bilateral pulmonary banding with the intention of controlling an ever increasing pulmonary blood flow. Peri-operatively, hypotension was treated successfully with multiple volume expansions and noradrenalin. Postoperatively, she was on Bi-level Positive Airway Pressure (BiPAP)-assist and prior to loss of output there were no clinical signs of primary respiratory failure (e.g. inadvertent extubation). Arterial pH was 7.34, arterial saturation was 90%, pCO1 infusion was inadequate at the time of collapse, remains unknown. Furthermore, autopsy revealed an immature lung parenchyma, atelectasis of part of the basal lobes and small inflammatory areas in both lungs. These pulmonary findings might also have contributed to the cardiopulmonary collapse.Autopsy confirmed the diagnosis and concluded that the lumen of the ductus arteriosus was small with a diameter of less than three millimeter. Whether this was too small to maintain systemic circulation and whether prostaglandin E2 and a decrease in renal rSO2 1 h before loss of output , volume expansion or perhaps emergency surgery. Furthermore, it might be useful to use predefined upper and lower limits of cerebral and renal oxygen saturation, a principle that was recently suggested in a large trial with preterm infants [2. In this population it might be more useful to use limits below which histological and biochemical changes in tissue have been reported, i.e. below 44% [In the current cases we did not respond to changes in cerebral and renal rSO infants . Due to elow 44% .In conclusion, in infants with duct-dependent congenital heart disease, a significant change in cerebral and/or renal oxygen saturation from baseline as measured by NIRS may be an early indicator of a sudden, unexpected clinical deterioration, which eventually could lead to cardiac arrest and death. Increased awareness and thorough scrutiny of the patient are required when such changes in cerebral and/or renal oxygen saturation are observed.


P < 0.001, respectively). The mean phasic resistivity decreased progressively from normal to heterogeneous and dense scar regions . Moreover, myocardial resistivity and phase angle correlated significantly with the degree of local fibrosis . Myocardial infarcted regions with greater fibrotic content show lower mean impedance values and more depressed systolic-diastolic dynamic impedance changes. In conclusion, this study reveals that differences in the degree of myocardial fibrosis can be detected in vivo by local measurement of phasic systolic-diastolic bioimpedance spectrum. Once this new bioimpedance method could be used via a catheter-based device, it would be of potential clinical applicability for the recognition of fibrotic tissue to guide the ablation of atrial or ventricular arrhythmias.Myocardial electrical impedance is a biophysical property of the heart that is influenced by the intrinsic structural characteristics of the tissue. Therefore, the structural derangements elicited in a chronic myocardial infarction should cause specific changes in the local systolic-diastolic myocardial impedance, but this is not known. This study aimed to characterize the local changes of systolic-diastolic myocardial impedance in a healed myocardial infarction model. Six pigs were successfully submitted to 150 min of left anterior descending (LAD) coronary artery occlusion followed by reperfusion. 4 weeks later, myocardial impedance spectroscopy (1–1000 kHz) was measured at different infarction sites. The electrocardiogram, left ventricular (LV) pressure, LV dP/dt, and aortic blood flow (ABF) were also recorded. A total of 59 LV tissue samples were obtained and histopathological studies were performed to quantify the percentage of fibrosis. Samples were categorized as normal myocardium (<10% fibrosis), heterogeneous scar (10–50%) and dense scar (>50%). Resistivity of normal myocardium depicted phasic changes during the cardiac cycle and its amplitude markedly decreased in dense scar (18 ± 2 Ω·cm vs. 10 ± 1 Ω·cm, at 41 kHz;  Myocardial electrical impedance is a biophysical marker of the state of integrity of the myocardial tissue  changes of myocardial resistivity in the Guide for the Care and Use of Laboratory Animals: Eighth Edition .The study protocol was approved by the Animal Care and Use Committee of our institution and conformed to the The study began after stabilization of the level of anesthesia and the hemodynamic parameters. Then, the ECG, LVP, ABF and impedance signals were recorded during 4 s at each site. In each pig, we explored 8–11 myocardial impedance sites spaced 10 mm apart, beginning at the healthy region and extending toward the infarcted area. At the end of the study the animals were euthanized by administration of an intravenous KCl overdose and the heart was removed.−1·min−1). Continuous infusion of lidocaine at a rate of 1 mg/kg/h  was used through the procedure. Systemic sodium heparin was injected IV (150 UI/kg) 5 min prior to percutaneous sheath placement.Eight female domestic swine (Landrace-Large White cross) weighing 33 ± 2 kg were submitted to two interventions spaced 30 days. The first intervention aimed at inducing an acute myocardial infarction. Animals received 400 mg oral amiodarone and 500 mg aspirin from 2 days before to 7 days after infarct induction. They were premedicated (midazolam 0.6 mg/kg and ketamine 12 mg/kg), anesthesized (propofol 2–4 mg/kg), and maintained with sevoflurane inhalation (2.5–3.5%). After endotracheal intubation animals were mechanically ventilated. Analgesia was maintained with a perfusion of remifentanil  was placed percutaneously into the femoral artery. To better mimic the clinical human scenario of a reperfused infarction, a coronary artery occlusion-reperfusion was performed. The infarction created with this models is characterized histologically by surviving strands of myocardium interwoven with fibrotic scar. A small modification of the Sasano model was used  was advanced into the left ventricle (LV) to measure the LV pressure. A conventional ECG lead was continuously recorded. The thorax was opened through a midsternotomy and the heart was suspended in a pericardial cradle. An ultrasonic flow probe was carefully deployed around the aortic root to monitor the aortic blood flow (ABF).In all cases we recorded the conventional ECG lead II , the LV pressure (Nihon Kohden) and the ABF . All signals were digitized at 1 kHz  and stored for subsequent offline analysis. The first derivative of the LV pressure was also calculated.The electrical impedance of the myocardium reflects an overall estimation of the intra- and extra-cellular resistances and the cell membrane capacitance  and the mean value of phase angle during the entire cardiac cycle. Thereafter, an analysis of the resistivity changes in relation to the LV pressure (LV pressure-impedance curves) was also performed. In addition, to determine the time relationship between the ECG and the systolic-diastolic myocardial resistivity, we measured the time interval between the R wave peak and the moment at which resistivity reached its maximum value.H; 10–50% of fibrosis) and (3) dense infarct scar .To assess the correlation between the degree of fibrosis in the infarcted region and the magnitude of local tissue impedance, we obtained myocardial samples in the same sites of impedance measurements. These sampling sites were marked with black ink after each myocardial impedance measurement to ensure an appropriate identification of the biopsies during tissue processing. The specimens were fixed in 10% buffered formalin, embedded in paraffin and sliced (4-μm thickness) perpendicularly to the epicardial surface up to the half of the sample block Figure . The perpost-hoc comparisons. Pearson's correlation between tissue fibrosis and impedance (resistivity and phase angle parameters) were calculated. A P-value < 0.05 was considered statistically significant. Statistical analyses were performed using the software SPSS v.22.0 .Data were expressed as mean ± standard error of the mean (SEM). Differences in the study variables were assessed by the analysis of variance (ANOVA) with Bonferroni correction for n = 6) completed their allotted follow up and were used for the study. As shown in Figure Two animal died during acute coronary occlusion due to irreversible ventricular fibrillation. The remaining animals (P < 0.001). Moreover, phase angle spectrum showed a negative relaxation which was maximal at about 307 kHz. Regions with heterogeneous scar tissue (10–50% of fibrosis) showed a similar trend of changes  although with a lower mean value  and a less marked phase angle relaxation. In contrast, sites with dense fibrosis presented an almost flat resistivity spectrum  with lower mean resistivity values . Likewise, the phase angle relaxation vanished in the dense infarct scar.Figure Figure r = −0.86 at 1 kHz, P < 0.001) and with a less negative phase angle deviation . Table As illustrated in Figure As shown in Figure P < 0.05) with an holosystolic plateau. The heterogeneous infarct scar zones attained their maximal resistivity peak at a delay similar to healthy myocardium.Analysis of the temporal relationship between the myocardial impedance and the ECG showed that the systolic-diastolic resistivity curve of healthy myocardial regions presented its maximal peak shortly after the R wave. By contrast, Figure D: 214.7 ± 44.2 mmHg·Ω·cm, ISH: 655.4 ± 160.7 mmHg·Ω·cm, N: 665.5 ± 137.8 mmHg·Ω·cm; p < 0.05 ISD vs. ISH and p < 0.01 ISD vs. N). These changes were comparable among the different studied frequencies.The temporal relationship between the whole cardiac mechanical activity and the concurrent changes in regional myocardial impedance can be better analyzed by constructing the LV pressure-impedance (LVPI) curves. As illustrated in Figure This study reveals that the degree of fibrotic deposition in the infarcted myocardium is a direct determinant of both the local decrease in tissue impedance and the attenuation of systolic-diastolic impedance oscillations.in situ porcine heart  could also be detected by means of bioimpedance methods in atrial or ventricular level. Thus, recognition of local fibrosis by endocardial catheter mapping would improve the yielding of radiofrequency catheter ablation of either atrial or ventricular arrhythmias.in vitro calibration measurements using the 4-needle electrode probe in contact with blood showed much lower impedance values with completely flat impedance spectrum.The impedance measurements described in this study were obtained with an intramural 4-needle electrode probe in the open-chest swine model in order to achieve optimal recording sensitivity and accessibility to tissue samples. Due to the thinning of the left ventricle in the sites of infarction we cannot entirely exclude that the impedance spectrum at those site could be more flat due to the short distance between the blood volume in the ventricle and the tip of the 4-needle electrode. Theoretically, this could affect the decrease in the systolic-diastolic impedance values. However, On the other hand, this method is an invasive approach precluding direct clinical use until an intracavitary approach based on endocardial contact electrocatheter probe is developed. We have previously reported in the swine model, that the changes in myocardial resistivity induced by coronary occlusion can be successfully detected with an electrocatheter based approach in the closed chest (Warren et al., As compared with the normal myocardium, the local impedance of healed myocardial infarction tissue shows lower mean values and depressed systolic-diastolic oscillations. These changes have their maximal expression in infarcted regions with greater fibrotic content. Once this new bioimpedance method can be implemented in a catheter-based device it might have potential clinical applicability in the detection of fibrotic tissue to guide the ablation of atrial or ventricular arrhythmias.JC, RB, and JR conception and design of research; GA, EJ, TG, RB, JR, and JC performed experiments; GA and EJ analyzed data; GA, EJ, and JC interpreted results of experiments; GA and EJ prepared figures; GA, EJ, and JC drafted manuscript; GA, EJ, TG, RB, JR, and JC edited and revised manuscript. GA, EJ, TG, RB, JR, and JC approved final version of manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


A 23-year-old African American woman with a past medical history of systemic lupus erythematous (SLE), secondary hypertension, and end stage renal disease (ESRD) on hemodialysis for eight years was stable until she developed symptomatic severe mitral regurgitation with preserved ejection fraction. She underwent a bioprosthetic mitral valve replacement (MVR) at outside hospital. However, within a year of her surgery, she presented to our hospital with NYHA class IV symptoms. She was treated for heart failure but in view of her persistent symptoms and low EF was considered for heart and kidney transplant. This was a challenge in view of her history of lupus. We presumed that her stenosis of bioprosthetic valve was secondary to lupus and renal disease. We hypothesized that her low ejection fraction was secondary to mitral stenosis and potentially reversible. We performed a dobutamine stress echocardiogram, which revealed an improved ejection fraction to more than 50% and confirmed preserved inotropic contractile reserve of her myocardium. Based on this finding, she underwent a metallic mitral valve and tricuspid valve replacement. Following surgery, her symptoms completely resolved. This case highlights the pathophysiology of lupus causing stenosis of prosthetic valves and low ejection cardiomyopathy. Systemic Lupus Erythematosus (SLE) is an autoimmune disorder resulting in multisystemic inflammatory damage mediated by the production of autoantibodies and immune complexes against a variety of self-antigens.The routine use of Doppler echocardiography in the evaluation of SLE mediated heart damage has disclosed a higher prevalence of patients with cardiac abnormalities than previously thought, given the high prevalence of clinically silent disease.The use of dobutamine stress echocardiogram in the setting of nonischemic cardiomyopathy can be a very helpful tool to assess the inotropic contractile reserve of myocardium and predict superior outcomes.A 23-year-old African American woman with a past medical history of systemic lupus erythematous, secondary hypertension, and end stage renal disease (ESRD) on hemodialysis for eight years was doing well. She developed progressive shortness of breath and was diagnosed with severe mitral regurgitation with preserved ejection fraction. She underwent successful bioprosthetic mitral valve replacement. About 6 months following surgery, she started feeling exertional shortness of breath and a year later she presented to our emergency department with NYHA class IV symptoms. Patient's heart rate was 86 bpm, blood pressure was 153/101, and respiratory rate was of 24 breaths per minute and she was afebrile. On auscultation, a holosystolic murmur and loud P2 were appreciated at the left lower sternal border. On ECG, there was left ventricular hypertrophy (LVH) with secondary repolarization abnormality .The patient's hemoglobin was 5.8 gm/dL and her hematocrit was 17.9%, serum BNP was >4700 pg/mL, and negative cardiac biomarkers, positive dsDNA antibody, positive ANA, and low C3 and C4 levels were also present.2. The left ventricular systolic function was severely decreased with global cardiomyopathy and ejection fraction <20%. Severe tricuspid valve regurgitation was also seen. Patient was treated with hemodialysis, furosemide, metoprolol, nifedipine, and transfused 2 units of PRBCs, and started on prednisone and hydroxychloroquine. She was treated for heart failure but in view of her persistent symptoms and extremely low EF was considered for heart and kidney transplant.On echocardiogram, the bioprosthetic mitral valve was found with thickened calcified leaflets, restricted mobility, and severe prosthetic stenosis by Doppler, with a mean gradient of 21 mmHg and a prosthetic valve area of 0.45 cm2 estimated by Hakki formula. A dobutamine stress echocardiogram was performed to evaluate the contractile reserve of the left ventricle and showed dramatically improved ejection fraction to more than 50%. Because of these findings on dobutamine stress echocardiogram, patient was considered for redoing valve surgery rather than pursuing for transplant. She underwent successful mechanical mitral and tricuspid valve replacement. Postoperative period and discharge were uneventful. Her symptoms improved and she returned to college to proceed with the routine activities. A follow-up echocardiogram after a month showed normal LV cavity size with ejection fraction of 60% and normal functioning prosthetic valves.Cardiac MRI showed global hypokinesis, IVC, and hepatic vein dilation consistent with tricuspid regurgitation, severe mitral stenosis, marked atrial dilatation of 6.5 cm, and marked ventricular dilatation of 7.7 cm. Cardiac catheterization showed normal coronaries and LVEDP was 5 mmHg, with LVEF of 25% with global hypokinesis and no LV-Ao gradient. On right heart catheterization, a mean RA pressure of 9 mmHg, RV of 34 mmHg, and PA of 49/27 mmHg and mean of 36 mmHg, with a wedge pressure of 27 with V 28 mmHg, were found. The patient had a mean gradient across her mitral valve of 17.24 mmHg and her mitral valve area was 0.63 cmWe herein describe a young patient with systemic lupus erythematous (SLE) and ESRD developing severe MR. SLE is an autoimmune disorder resulting in multisystemic inflammatory damage mediated by the production of autoantibodies and immune complexes against a variety of self-antigens , 2. TherThe routine use of Doppler echocardiography in the evaluation of SLE mediated heart damage has disclosed a higher prevalence of patients with cardiac abnormalities than previously thought, given the high prevalence of clinically silent disease –11.Among valvular heart disease, mitral regurgitation is the most common manifestation , 5, 10. However, this drop in EF is very marginal unlike the case in our patient. In our patient, lupus was in control making lupus myocarditis low on the differential. We hypothesize that the low EF was secondary to mitral stenosis. This is from altered loading condition with decreased preload and increased vasoconstriction from increased afterload.Lastly, the use of dobutamine stress echocardiography in cardiomyopathy has shown prognostic implications in nonischemic cardiomyopathy , 18. We This case illustrates and discusses three key aspects. First, it emphasizes the influence of lupus on heart causing predominantly valvular disorders: mitral regurgitation of native valve and stenosis of bioprosthetic valves. Secondly, it highlighted the pathophysiology of mitral stenosis: native or prosthetic, both causing a decreased preload and increased afterload situation causing a low ejection fraction. Finally, the use of dobutamine stress echo was a very helpful tool to assess the inotropic contractile reserve of cardiomyopathy and predict superior outcome. In our patient, the redo of valve surgery corrected the pathophysiology of stenosis and strikingly improved her myocardial function. She did extremely well clinically and we could elude an aggressive, unnecessary, and probably impractical heart transplant surgery in this young woman with heart failure.


Pulmonary embolism (PE) represents a prevalent cause of morbidity and mortality in the United States, with approximately 600 000 cases diagnosed annually. The mortality rate for untreated PE is as high as 30%. Right ventricular (RV) dysfunction is a sign of possible adverse outcomes with right-sided heart failure being the usual cause of death from PE. There is a spectrum of clinical presentations associated with PE diagnoses, from incidental and asymptomatic to rapid hemodynamic collapse. Despite successes in identifying patients with “high-risk” PEs for aggressive thrombolytic interventions and “low-risk” PEs for outpatient anticoagulation, a significant lack of consensus exists regarding intervention modalities for PEs identified as “intermediate risk” or “submassive,” defined as normotensive (systolic blood pressure ≥90 mm Hg) with acute RV dysfunction and myocardial injury. In this case series, we review the management and outcomes of 2 patients with submassive PEs and sustained tachycardia in the setting of normal blood pressures, and we address the need to recognize tachycardia as an ominous RV compensatory sign, indicative of impending hemodynamic collapse, that should lead to aggressive therapy with vascular intervention. This category, in particular, has raised a number of debates regarding optimal management, including identification of those most likely to decompensate, even in the setting of systemic anticoagulation.10Current management guidelines state systemic administration of antithrombolytic therapy be reserved for patients with “high-risk” or “massive” PE causing hemodynamic instability.11 Furthermore, in the setting of acute PE, the presence of RV dysfunction without evidence of hemodynamic compromise has been associated with a 2- to 10-fold higher risk of early mortality, compared with normotensive patients with acute PE but without RV dysfunction.6Multiple scoring systems have been developed to risk stratify patients having increased risk of PE-related outcomes. The Pulmonary Embolism Severity Index is a clinical model that identifies low-risk PE patients for outpatient treatments. The Wells and revised Geneva scores can be used to objectively identify the risk of a suspected PE, both incorporating heart rate. When the pulmonary arterial pressures increase as a result of an obstruction by an embolus, the RV afterload increases, in turn resulting in RV dilation, and ultimately decreased cardiac output and possible death.12 Bova et al13 developed a statistically significant prognostic grading system to predict PE-related complications in intermediate-risk PE populations, which combined clinical presentation, RV dysfunction, and myocardial injury. Predictors of complications included systolic blood pressure 90 to 100 mm Hg, heart rate ≥110 beats per minute (BPM), and elevated cardiac troponin levels.13 This study found that the combination of the above-mentioned parameters predicted a 7-fold increase in the risk of an adverse 30-day PE-related outcome.13 Findings on echocardiogram suggest RV dysfunction include RV dilatation, RV hypokinesis with apical motion sparing, flattening or paradoxical movement of the interventricular septum toward the LV in diastole, pulmonary hypertension, and tricuspid regurgitation.14 Computed tomography pulmonary angiography (CTPA) is currently the gold standard in diagnosing PEs. A RV/LV diameter ratio is also easily determined by CTPA, and the 30-day mortality rate is 15.6% in patients with CTPA and RV/LV >0.9 compared with 7.7% in patients without RV enlargement.15Markers of RV dysfunction, such as echocardiogram, spiral CT, BNP, and myocardial injury (positive cardiac troponin testing), have low predictive values for PE complications when used alone.9Clinical suspicion for the presence of RV failure should be for every patient admitted with acute PE, regardless of initial hemodynamic stability.Herein, we review 2 similar cases that involved presentations of intermediate-risk pulmonary emboli, where both patients displayed persistent tachycardia in the setting of normal blood pressures. We review the outcomes of both cases, and we discuss why persistent tachycardia is a compensatory measure indicative of impending hemodynamic collapse in the setting of PE.2) 90% on room air, and a persistent heart rate of 138 BPM. A 2-liter bolus of lactated Ringer’s solution was administered as well as 0.5 mg of oral lorazepam with no consequent change in heart rate. The patient denied any pain or distress on bedside examination; physical examination was remarkable for increased tone and spasticity of lower extremities with 5/5 strength and normal light touch. Laboratory values were significant for a pro-BNP of 2898 pg/mL, and an arterial blood gas result of pH 7.4, partial pressure of carbon dioxide (pCO2) 33.4, and partial pressure of oxygen (PaO2) 53.0. Complete blood count, thyroid function panel, and basic metabolic panel collected that morning were unremarkable. Electrocardiogram was significant for sinus tachycardia, and Doppler studies of the lower extremities were negative for evidence of deep vein thrombus bilaterally. Subsequently performed echocardiogram revealed normal LV systolic function, ejection fraction of 55%, flattened septum in diastole, and mildly dilated RV size with severely reduced systolic function, moderate tricuspid regurgitation, and a mild increase in pulmonary artery pressures to 42 mm Hg. CTPA was positive for extensive pulmonary emboli throughout the distal left pulmonary artery extending into the upper and lower lobe branches , troponin T (0.10 mg/mL), and creatinine kinase-MB index (66%). Complete blood count and basic metabolic panel were unremarkable. Electrocardiogram was significant for sinus tachycardia. Chest X-ray was unremarkable. Lower extremity Doppler scans were ordered and were noted to be positive for acute deep venous thrombosis in the right popliteal, posterior tibial, and peroneal veins. While the echocardiogram was pending, the cardiac phase of the CTPA allowed for the indirect assessment of RV function. On the CTPA the RV was dilated; the septum bowed with a LV/RV ratio greater than 2.0. The RV and LV diameters were manually measured as the maximum distance from the interventricular septum to the endocardial border, perpendicular to the long axis of each ventricle , and included previous incidence of a left lower extremity deep vein thrombus following a knee injury, managed with 6 months of anticoagulation, since completed. Her medication list at time of presentation consisted of levothyroxine and medroxyprogesterone acetate. Vital signs on admission were noted as follows: blood pressure 120/86 mm Hg, heart rate 136 BPM, respiratory rate 25 BPM, and SpOentricle . These fentricle .2 of 85%. She was ordered for 2 mg oral lorazepam, transferred to the intensive care unit, and placed on high-flow nasal cannula with improvement to SpO2 to 96%. Within 1 hour and 20 minutes of transfer, patient cardiac arrested.The patient was immediately put on a heparin drip (80 units/kg bolus then infusion starting at 18 units/kg/h) and admitted to the general medicine floor. Within 4 hours from the time of admission, the patient became acutely agitated, diaphoretic, and tachypneic, with vital signs as follows: 140/86 mm Hg, heart rate of 160 BPM, and SpOCardiopulmonary resuscitation was performed for 1 hour, with 100 mg of intravenous tissue plasminogen activator administered for her PE. The code was ultimately unsuccessful, and the patient subsequently passed.When the pulmonary vasculature is impaired with large acute pulmonary emboli, RV dysfunction commonly develops as a consequence of increased pulmonary vascular resistance. The increase in pulmonary artery pressure leads to an increase in RV afterload, RV dilation, and progressive RV failure. This results in reduced cardiac output and ultimately is the cause of death in most PEs. As a compensatory measure, consistently elevated heart rates in patients with PE act to maintain cardiac output, with normotensive blood pressures and adequate systemic perfusion. This, however, cannot be sustained, as we report here with our patient case series.10 In the PIOPED II study, conducted between 2001 and 2003, multidetector CTPA had a sensitivity of 83% and a specificity of 96%, and when used with CT venography of the lower limbs, this increased to 90% and 95%, respectively.16 The PROJECT  study also assessed RV dysfunction by CT and used predefined cutoff point to determine abnormal versus normal RV function.17The clinical evaluation of these patients is of paramount importance to establish early diagnosis. Data from the ICOPER registry have also shown that patients with RV dysfunction on echocardiogram have an increased risk of death.10 Patients were randomized to receive tenecteplase plus heparin versus placebo plus heparin. The use of anticoagulation alone in normotensive patients with PE was supported, but the use of thrombolysis in this intermediate-risk cohort could not be supported uniformly, given an elevated risk-benefit ratio involving catastrophic events, such as major intracranial bleeding.10 Separate meta-analyses reiterate this elevated risk of bleeding with thrombolytic management of intermediate-risk PEs but suggest that risk of bleeding events may be reduced in patients less than 65 years of age.17The PEITHO trial, the largest randomized, double-blinded trial published to date, investigated the role of thrombolysis in intermediate-risk PE patients, which was defined as the presence of RV dysfunction on echocardiography or CT together with myocardial injury.19 In this study, clot burden on CTPA, and not echocardiography, was used to define intermediate PE. Only 20% of the patients showed RV dilation on initial echocardiogram.18 The thrombolytic group demonstrated significantly lower pulmonary artery systolic pressures, but the clinical implications of these findings are unclear.Several recent studies have suggested that treatment with thrombolysis plus anticoagulation had significantly improved clinical outcomes. The MOPPETT trial, a randomized, placebo-controlled trial, compared the effects on reduction of pulmonary artery pressure with treatment with heparin plus tissue plasminogen activator versus heparin alone on patients with intermediate-risk PE.We discuss here the management of 2 recent cases of pulmonary emboli, both stratified into an “intermediate-risk” category secondary to evidence of right heart strain with normal blood pressures, with the only clinical indicator of hemodynamic compromise, from massive clot burden in the pulmonary vasculature, being persistent tachycardia. The patient in the first case received emergent catheter-directed thrombolytic therapy and had an uneventful course. The patient in the second case received heparin following admission, with brief documentation of possible consideration for nonurgent vascular intervention with catheter-directed thrombolytic therapy. Her cardiovascular status significantly worsened over the course of 4 hours following admission, and despite late administration of systemic thrombolytic therapy given as a resuscitative effort, the patient ultimately expired.20Despite being normotensive, tachycardia is an ominous sign of possible impending cardiovascular collapse. It suggests severe reduction in RV function, with a very low RV stroke volume with the blood pressure being maintained by the elevated heart rate, with heart rate increase being proportional to the degree of RV dysfunction. Rapid restoration of pulmonary artery flow can improve pulmonary perfusion, reduce pulmonary pressures, and prevent cardiac failure. Mechanical techniques and catheter-directed thrombolysis will result in quicker clot dissolution than systemic thrombolysis.With recognition of tachycardia as an early indicator of hemodynamic compromise and an unsustainable compensatory measure of diminished RV cardiac reserve, earlier consideration for catheter-directed thrombolytic therapy should be initiated in patients with tachycardia and submassive PE before onset of hemodynamic instability requiring salvage measures with systemic thrombolytic therapy.


Q-waves on 12 lead ECG is considered a marker of a large and/or transmural myocardial infarction (MI). Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) accurately identifies myocardial infarction and has become the gold standard for the assessment of myocardial viability. However, CMR is not universally available and clinicians often have to make assumptions based solely on presence/location of Q waves.To determine the diagnostic accuracy of Q-waves on 12 lead ECG to identify the presence and location of myocardial scarring. To ascertain the CMR predictors of Qwave.Data was collected on consecutive patients suspected ischaemic heart disease (from April 2013 to Mar 2014). Exclusion criteria-presence of any non-ischaemic heart disease that may cause Q-Wave. Pathological Q-waves - deflection > 25% of the subsequent R wave, or being > 40 ms in width and > 2 mm in amplitude in >1 corresponding lead. Q waves in any 2 or more precordial leads from V1-V4 reflected LAD territory. A comprehensive CMR protocol was used. Transmural infarction was defined as >50% LGE. Univariate and multivariate logistic regression analyses were performed to determine the relation between the presence/absence of Q waves and CMR variables.498 patients were included . 290 patients demonstrated MI, 157 were transmural and 133 sub-endocardial based on CMR LGE. The overall diagnostic accuracy of Q-wave as a marker of transmural MI was 66% and the diagnostic accuracy of Q waves as a predictor of previous MI  was only 55%. 126 had pathological Q-waves on 12 lead ECG, 40% had LAD territory Q waves, 55% non-LAD and 5% a combination. Of those with LAD Q waves, 68% demonstrated LAD territory LGE and in non-LAD Q waves, 67% demonstrated a non-LAD territory infarct by LGE.Univariate predictors of the presence of a Q wave included any LGE, spatial extent of scar tissue, transmurality(50 or 75% LGE), and total scar score. On multivariate analysis, total scar score and >75% thickness LGE remained significant for prediction of the presence of a Q wave on the ECG.Our study demonstrates that the presence of pathological Q-waves on 12 lead ECG is not only a poor marker of myocardial scarring, but also a poor predictor of viability when compared to CMR. The study also highlights presence or absence of a Q wave on the ECG correlates only with total scar score and >75% wall thickness LGE. Our study also demonstrates the limitation of Q-wave in localizing the coronary artery territory. In their clinical decision making process, clinicians needs to be aware of the limitations of ECG Q-waves.


The purpose of this study was to investigate Korean elite soccer players’ myocardial function using the conventional and advanced speckle tracking imaging to compare the difference with the normal controls. We used 2D echocardiography speckle tracking echocardiography (STE) to evaluate LV regional strain in 29 elite soccer players compared to 29 age-matched healthy controls. Conventional, tissue Doppler, and STI echocardiography was performed, for strain at base and apex, rotation and torsion. There is no difference in longitudinal strain , and basal radial strain. However, the significant increases were noticed in basal circumferential strain , apical radial strain , and apical circumferential strain in soccer players . Soccer players showed the higher rotation at base , and apex , higher torsion . In conclusion, the elite soccer players’ heart demonstrated the unique ventricular adaptation. These alterations could benefit the cardiovascular adjustment to exercise without much loss of myocardial energy expenditure. During exercise, the heart endures some alteration as a result of increase heart rate and cardiac output234Athletes show an improvement in myocardial diastolic properties and supernormal left ventricular diastolic functionThe previous echocardiographic studies of athlete’s cardiac function have demonstrated that prolonged exercise is concomitant to a shift in diastolic filling from early to late diastole, a change in ventricular dimensions and volumes, a reduction in systolic function, and the development of wall-motion abnormalities in the LV78The tissue Doppler imaging is the most suggested method for quantitative and regional analysis of myocardial function. In addition, recent development of 2D ultrasound speckle tracking echocardiography provided capability of non-invasive evaluation for strain, and assessment of LV torsion.Investigations of elite athlete’s heart have recently provided relevant information on the apex myocardial reserve of the left ventricleThe purpose of this study was to investigate Korean elite soccer players’ myocardial function using the conventional and advanced method with 2D speckle tracking echocardiographic imaging to compare the difference with the healthy normal controls.This study included 29 highly trained Korean elite athletes of soccer players, 29 age-matched healthy sedentary controls. The elite soccer players participated in World-cup soccer competition. No one had any past history of cardiovascular disease or related problem or arrhythmia. This study was approved by The Institutional Review Board at Yonsei University. The written informed consent was obtained from each of the participant or their legal guardian for this data publication. All the followed methods were performed in accordance with the relevant guidelines and regulations in Yonsei University.The quantitative analysis of the left ventricle was performed according to the current recommendations and guideline of the American Society of Echocardiography and the European Association of Echocardiography, using a high quality echocardiography machine , equipped with a 2.5 MHz probe. LV EF and stroke volume were derived as the average of the measurements in apical four chamber and two chamber views according to the modified Simpson’s rule. LV mass was indexed to height. Relative diastolic wall thickness was determined as twice the posterior wall thickness divided by LV end-diastolic diameter.Left atrial volume was determined as the average of measurements in apical four chamber and two chamber views and indexed to body surface area.Transmitral pulsed wave Doppler and tissue Doppler velocities were recorded in the apical four chamber view at septal and lateral annuli.  and 3Speckle tissue tracking was performed according to validated methods on three consecutive cardiac cycles of two dimensional LV images in apical and parasternal view.2D strain variables were measured in the parasternal short axis and apical four chamber views.2D echocardiographic images at apical 4- and 2- chamber views were obtained using conventional gray scale, during breath hold with a stable ECG recording. The three consecutive heart cycles were recorded and averaged.Advanced tissue speckle tracking echocardiographic images were recorded at a rate over 50 frames /sec to investigate the myocardial strain and its rate. Two-dimensional images of apical 4 chamber view were recorded for longitudinal strain, while those of parasternal short axis view were acquired for radial and circumferential strain. Offline speckle tracking process was conducted with acoustic markers using dedicated software. The endocardial and epicardial borders were traced manually, the middle-myocardial border automatically defined as the midline between the endocardial border and epicardial border. These three contours were tracked frame by frame throughout the cardiac cycle.LV torsion was assessed by calculation. The rotational movement as the apex moves with respect to the base about the LV long axis, by speckle tracking.Averaged LV rotation and rotational velocities from the base and apex were used for calculation of LV torsion.t test was performed to compare the parameters. Statistical significance was inferred by a p value less than 0.05, using Statistical Package for the Social Sciences (SPSS) for Windows software version 20.0 .Data are presented as mean + SD. Paired student The soccer players exhibited increased height, weight, body surface area, and lower hear rate. The systolic and diastolic blood pressures were not dissimilar.  LV mass LV volume at systole and diastole, and LA volume in systole and diastole,  RV systoWith conventional trans-mitral Doppler parameters, the early diastolic velocity of E was not statistically different, however, the late diastolic velocity of A was decreased, the ratio of E/A was increased, deceleration time was increased in soccer players, pressure half time was not dissimilar .As a marker of advanced diastolic function with TDI, the septal early diastolic E′ was not different, however, septal late diastolic A′, septal systolic S′ were decreased, the ratio of conventional early diastolic flow velocity per septal myocardial early diastolic tissue Doppler velocity of E/E′ was decreased in athletes. Lateral early diastolic E′ was increased, lateral late diastolic A′, lateral systolic S′ were decreased, and the ratio of lateral E/E′ was significantly decreased in athletes .With advanced 2D speckle tracking imaging, myocardial strain analysis was performed. There is no difference in longitudinal strain , and basal radial strain . HoweverMoreover, soccer players showed the higher rotation at base , and apex  . The calA supernormal cardiac function in athlete’s heart, especially about LV diastolic pattern, has been described11126This study demonstrated several significant differences between elite soccer players and healthy controls. Mitral inflow Doppler A wave was lower in soccer players with decreased tissue Doppler A′, which explained a shift in the pattern of the diastolic filling from late to early diastole, and this shift may reflect in a fast submissive atrial emptying. The increased measurement of tissue Doppler E′, S′, and decreased measurement of E/E′ in elite soccer players, supported the previous researches about supernormal diastolic function of athletes as wellThe contraction of myocardium induces a systolic increase in LV normal strains, longitudinal shortening, radial thinning, and circumferential shortening. Moreover, due to helical orientation of myofibrils, contraction also induces shear strains within the myocardium, including longitudinal-radial, circumferential-radial, and circumferential-longitudinal elementsFor our result of elite soccer players, the longitudinal strains during systole were similar to controls. At the base, circumferential strain was increased. At the apex, both of radial and circumferential strains were all significantly increased. This result suggested the LV strain of circumferential myofibril is the most sensitive, then, apical circumferential and radial orientation is much delicate than the base. In addition, this result supported the previous researches that the enhanced diastolic alteration during exercise is because of the more dynamic untwisting motion of the apex in LV level14The rotation is also significantly increased in athletes at the base and apex in this study.et al. insisted that the magnitude of increase in twisting and untwisting rates during exercise was significantly greater than the corresponding changes in LV length and radiuset al. reported that LV torsion increased at post-completion of the race with indoor rowing playersTorsion calculated from apical and basal rotation is higher in soccer players. LV torsion depends on the LV wall thickness to LV radius ratio, and afterload. Notomi Although, longterm precise measurement is yet limited, the 2D-derived LV torsion is a feasible, sensitive and specific parameter of myocardial function assessment in elite soccer player for athlete’s heart.The elite soccer players’ heart demonstrated the unique ventricular adaptation including higher basal circumferential strain, apical radial and circumferential strain, higher basal rotation and apical rotation, and torsion. These alterations could benefit the cardiovascular adjustment to exercise without much loss of myocardial energy expenditure.How to cite this article: Eun, L. Y. and Chae, H. W. Assessment of myocardial function in elite athlete's heart at rest - 2D speckle tracking echocardiography in Korean elite soccer players. Sci. Rep.6, 39772; doi: 10.1038/srep39772 (2016).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Although musculoskeletal effects in resistance training are well described, little is known about structural and functional cardiac adaption in formerly untrained subjects. We prospectively evaluated whether short term high intensity (resistance) training (HI(R)T) induces detectable morphologic cardiac changes in previously untrained men in a randomized controlled magnetic resonance imaging (MRI) study.80 untrained middle-aged men were randomly assigned to a HI(R)T-group  or an inactive control group . HI(R)T comprised 22 weeks of training focusing on a single-set to failure protocol in 2–3 sessions/week, each with 10–13 exercises addressing main muscle groups. Repetitions were decreased from 8–10 to 3–5 during study period. Before and after HI(R)T all subjects underwent physiologic examination and cardiac MRI .2; RV: 77.0±15.5 to 78.7±15.1 ml/m2) and mass  significantly increased with HI(R)T . Mean LV and RV remodeling indices of HI(R)T-group did not alter with training , indicating balanced cardiac adaption. Indexed LV (48.4±11.1 to 50.8±11.0 ml/m2) and RV (48.5±11.0 to 50.6±10.7 ml/m2) stroke volume significantly increased with HI(R)T (p<0.001). Myocardial strain and strain rates did not change following resistance exercise. Left atrial volume at end systole slightly increased after HI(R)T , the ratio to end-diastolic LV volume at baseline and post-training was unchanged .Indexed left (LV) and right ventricular (RV) volume (LV: 76.8±15.6 to 78.7±14.8 ml/m22 weeks of HI(R)T lead to measurable, physiological changes in cardiac atrial and ventricular morphologic characteristics and function in previously untrained men.ClinicalTrials.gov), NCT01766791.The PUSH-trial is registered at the US National Institutes of Health ( Resistance training (RT) is an increasingly popular method of conditioning for recreational purposes and in competitive athletes. In 2011, about 24% of middle-aged and older adults in the US performed strength-training activities at least twice a week [Although the benefits of RT on the skeletal muscle are well established , the effThe Physical adaptions in Untrained on Strength and Heart (PUSH) study was conducted in collaboration of the Department of Radiology and the Institute of Medical Physics (IMP), Friedrich-Alexander University Erlangen-Nuremberg (FAU), Germany. Study period was from April 2012 to July 2013. We conducted a 22-week randomized controlled exercise trial with a parallel group design, focusing on the effect of high intensity, single set resistance exercise protocols (HI(R)T) on functional and morphologic cardiac parameters in middle-aged (30–50 years old) untrained males compared to sedentary controls. Details of the whole PUSH trial have been described before .www.clinicaltrials.gov (NCT01766791).The study was approved by the institutional review board of the Faculty of Medicine of the Friedrich-Alexander-University (FAU) of Erlangen-Nuremberg (ethics application number 53_12 B) and written informed consent was obtained from all subjects. PUSH complied with the Declaration of Helsinki “Ethical Principles for Medical Research Involving Human Subjects”. The study was registered at Myocardial mass (MM) changes as determined by cardiac MRI from baseline to the end of the intervention after 22 weeks of exercise.Changes in end-diastolic volume (EDV) as determined by cardiac MRI from baseline to the end of the intervention after 22 weeks of exercise.Originally, we planned to assess the effects of detraining on changes in myocardial mass and end-diastolic volume induced by 22 weeks of HI(R)T. Therefore, we intended to perform follow-up cardiac MRI examinations six months after the end of the training period. However, because most of the participants (n = 31) continued RT after the intervention period, reversibility of myocardial adaption was not tested.Sample size was determined  . We esti2, n = 1). Of the 123 men remaining, three were unwilling to be randomly allocated to a group and quit the study. Physical characteristics at baseline and post-training, profile of risk factors, and past medical history anamnesis are shown in Eligible study members were untrained  men between 30 and 50 years of age. Initially, two-thousand randomly selected men in the area of Erlangen (Germany), aged 30–50 years, were contacted using the citizen’s register of the municipality. Of those who responded 138 men were assessed for eligibility . All parStratified for age (4 stratas of 5 years), 120 participants were randomly assigned to three study arms by a uniform allocation rate (1 : 1 : 1): HI(R)T- (n = 40), control- (n = 40), and HI(R)T & protein supplementation-group (n = 40) . The latth week as a rest week. The exercise program consisted of two to three supervised sessions per week addressing the main muscle groups by 10–13 exercises out of a pool of 17 exercises conducted on resistance devices . We used a single-set-to-failure protocol with prescribed exercise intensity as a range of repetitions  that had to be accomplished under the premise of work to momentary muscle failure. The number of repetitions was consistently decreased from 8–10 to 3–5 repetitions during the training period. Daily data were recorded on duration and type of training activities performed throughout the study period. During the whole study period, the control group was requested to maintain their lifestyle and physical activity. Detailed exercise program and procedure has been described previously [Before the actual training period of HI(R)T-group there was a pre-phase consisting of two weeks initiation and four weeks of conditioning . Members of HI(R)T-group were then trained for 16 weeks with a linearly periodized resistance exercise protocol subdivided in 4-week phases with each 42; slice thickness, 6 mm; intersection-gap, 1.5 mm; repetition/echo time, 41.25 to 50.7/1.12 to 1.38 ms; flip angle, 61° to 75°; matrix, 105 to 156×192 to 256; pixel size, 1.5 to 2.8×1.2 to 2.0 mm2; number of reconstructed phases, 25; parallel acquisition acceleration factor of 2. Myocardial strain was assessed using a prototype balanced steady-state free-precession-based tagging sequence with the following image acquisition parameters: complementary spatial modulation of magnetization, field of view, 340×340 mm2; slice thickness, 6 mm; tag-spacing, 6 mm; repetition/echo time, 32.23/1.23 ms; flip angle, 20°; matrix, 77×256; PAT acceleration factor of 2.Cardiac MRI at baseline (before the introductory training) and post-training MRI was performed on a 1.5-T unit  using a six-channel phased-array surface and spine matrix receiver coil. Four-, three-, and two-chamber long- and short-axis cine images  were acqOutcome assessors were blinded to study subjects’ group assignment. All personal data was removed from cardiac MRI exams by the study nurse. Readers evaluated studies independently and in random order.2. Three-dimensional left ventricular analysis of myocardial strain was performed using semi-automatic software .Quantitative image analysis was performed using dedicated software . LV and RV functional analysis was performed in consensus by two observers with more than 5 (—) and more than 14 (—) years of experience in MRI. Tracing of the endo- and epicardial borders from base to apex was performed manually at end diastole and end systole. Papillary muscles and epicardial adipose tissue were excluded. All results were divided by BSA to minimize differences of myocardium parameters related to weight and height. LV wall thickness was defined as the average of six segment thickness measurements . We calculated the LV and RV remodeling index . An increased remodeling index is consistent with concentric hypertrophy, whereas a reduced remodeling index is indicative of isolated cavitary dilation . In addiStatistical analysis was performed using software . The primary analysis was intention-to-treat and involved all patients who were randomly assigned, independently of compliance or lost to follow-up. Normal distribution of variables was checked graphically and statistically (Shapiro-Wilks-Test). Change from baseline was analyzed and compared in HI(R)T- versus control-group in a linear mixed effects model with random intercept where measurement occasions are nested in patients. Patients who were lost to follow-up are considered to be missing at random conditional on the previous measurement occasions (MAR) and were included in the model via estimation of the covariance structure within maximum likelihood estimation. Mean changes from baseline ± standard errors are shown together with baseline values ± standard deviations. Differences in mean changes of HI(R)T-group versus control-group are presented with 95% confidence interval and error probability . Each shown result is inherently adjusted for baseline differences in considered outcome but not for other baseline values. Analyses adjusted for age, BMI, BSA and heart rate are not shown here, but yielded no substantially different results. A two-sided P-value of less than .05 was considered statistically significant.During the intervention period there were two drop-outs in the HI(R)T-group . No significant intra- or intergroup differences for baseline and post-training physical characteristics, risk factors, and past medical history were determined for HI(R)T and controls . In HIT-group after 22 weeks training by 2.8% and 2.2% . Mean va2). No subject exceeded normal limits for RV end-diastolic volumes (RV: 55–105 mL/m2).Parallel to enhanced myocardial mass in HI(R)T subjects, values for indexed LV and RV end-diastolic volumes were significantly higher (2.5% and 2.2%) after the intervention period compared to controls. Higher end-diastolic volumes were associated with greater LV and RV stroke volumes  and slightly smaller end-systolic volumes . Only one subject in the HI(R)T-group (LV: 99 ml) and three controls  were beyond normal LV ranges for healthy, male, non-athletic subjects (LV: 47–92 mL/mIn the HI(R)T-group changes in LV and RV myocardial mass were highly correlated with increments in end-diastolic volume . LV and RV remodeling indices in the exercise-group remained unchanged after 22 weeks of HI(R)T  compared to baseline values . This is indicative of balanced cardiac adaption . In addi2 ± 7.9 to 37.0 mL/m2 ± 8.4 (p = 0.411) with HI(R)T. In control- and HI(R)T-group ratios of indexed end-systolic LA volume to end-diastolic LV volume at baseline  and after the intervention  were comparable.Mean value for indexed maximum LA volume at end systole increased by 2.2% from 36.2 mL/mPeak systolic circumferential strain before and after the intervention period ranged between -10% to -25% without significant intergroup differences for HI(R)T- and control-group subjects . IntragrThis longitudinal cardiac MRI study shows that a relatively short period (22 weeks) of HI(R)T in previously untrained male subjects induces significant morphologic changes of the LV and RV.Previous cross-sectional echocardiographic –22 and MThe discrepancy between results found in our investigation and previous cross-sectional studies might in part be explained by differences in imaging modalities. Compared to echocardiography, cardiac MRI provides high quality images and is intrinsically three dimensional . Especially, evaluation of the RV myocardial mass and volume is limited using echocardiography ,24. CardIn the present study, there were no differences in the LV/RV ratios for volume and mass indices, indicating balanced cardiac adaption of both chambers. This is in contrast to a previous animal study in rats  postulat2 and RV, 16–36 g/m2, respectively) [Indexed LV and RV myocardial masses at baseline and after the training period were below previously reported mean values for healthy male subjects  ,28. We sctively) . None ofMean LV wall thickness of all study subjects at baseline (8.1 mm) is lower than that of previously reported reference values (8.8–9.0 mm) for healthy, male, non-athletic subjects ,30. ThisVentricular remodeling of HI(R)T-members in our investigation is accompanied by a balanced increase in LA dilation. However, LA enlargement in our study (2.2%) was lower than that observed in previously sedentary individuals after a comparable period of high-intensity interval training (13%)  and in lBesides the beneficial cardiovascular effects of regular resistance exercise training there is still uncertainty whether high-intensity RT is associated with cardiac maladaption. Post mortem investigations in athletes suffering from sudden cardiac death detected myocardial interstitial fibrosis  and animPhysiologic morphologic adaption in our study is supported by unremarkable electrocardio-graphic patterns before and post-training. Therefore, we hypothesize that the mentioned changes in protein expression are related to a physiological process with transient myocardial adaption leading to enhanced cardiac structure and function. This is supported by the findings of a concomitant increased expression of protective proteins described in the study by Dantas et al.  and an iLV and RV ejection fraction in our study slightly improved after HI(R)T. This finding is attributable to the larger EDV of hypertrophied ventricles.As our study comprises a relatively broad age range with a relevant distribution of physical characteristics, risk factor profile, and fitness level we hypothesize that physiologic cardiac adaptions to HI(R)T found in our investigation are generalizable to a large part of the population.Our study has several limitations. Because our study involved only volunteers, not clinically suffering from cardiac disease, intravenous contrast agent was not applied. Therefore, we could not measure delayed gadolinium-enhancement, indicating potential cardiac fibrosis. Risk factors (e.g. hypertension) and impact of medication in a small number of participants might influence study results although subgroup study analysis showed no statistically relevant effect. We performed MRI only at the beginning and end of the training or waiting period, so we do not have information about time specific effects on cardiac adaption in the course of the study. This is due to the high training effort for participants and methodical limitations. Because most of the study subjects continued RT after the intervention period, reversibility of myocardial adaption could not be tested. The long-term dynamics of myocardial adaption in HI(R)T need to be addressed in further studies. We did not perform MRI with exercise or pharmacological stress, which in part may explain the relatively wide range in end-systolic volume. We also did not perform a direct comparison to the effects of other types of training , known cardiac diseases (e.g. hypertrophic cardiomyopathy) or the abuse of anabolic substances to describe differences in cardiac adaption. We did not test participants for anabolic steroid abuse but all study subjects denied the use of illicit substances.This longitudinal cardiovascular MRI study suggests that a relatively short period of HI(R)T in previously untrained men is associated with physiological, significant changes in cardiac atrial and ventricular morphologic characteristics and function.S1 File(SAV)Click here for additional data file.S2 File(DOC)Click here for additional data file.S3 File(PDF)Click here for additional data file.S4 File(DOCX)Click here for additional data file.S5 File(DOCX)Click here for additional data file.S6 File(TXT)Click here for additional data file.S7 File(TXT)Click here for additional data file.


Left ventricular myocardial strain has been described as a potentially useful technique for evaluation and risk stratification of a range of acquired and congenital heart diseases. Tagged acquisition by cardiac MRI has been considered the reference standard for determining myocardial strain; however, this method can be time consuming and the tagged lines may not be visible throughout the cardiac cycle. Tissue Tracking software (Circle Cardiovascular Imaging®) is a post-processing method which allows measurements of myocardial strain based on cine cardiovascular magnetic resonance images without the need for additional sequences. Augustine et al. (JCMR 2013) have previously reported reasonable agreement between Feature Tracking (Tom Tec®) measurements for circumferential strain and tagging. We aimed to perform a similar comparison between Tissue Tracking software and tagging on a small cohort of normal volunteers.Cardiac MRI studies were performed with a 1.5 T unit  on 7 normal volunteers. Short-axis tagged MR images of the left ventricle were analyzed using HARP software  by the same observer, blinded to results of the alternate method. Steady state free precession (SSFP) cine images were analyzed with Tissue Tracking software (Circle Cardiovascular Imaging®) by two observers in consensus. The 2D peak circumferential strain (%) obtained by both techniques were compared using Bland Altman analysis for each of the 16 cardiac segments based on the American Heart Association classification for short axis images.There was reasonably good correlation between tagged acquisition and Tissue Tracking software. A total of 94 data points were included. The Bland-Altman plot is shown in Figure Tissue Tracking software provides a good surrogate for calculating 2D peak circumferential strain (%). A larger cohort is needed to further validate this new capability.


Cardiovascular disease in patients with end-stage renal disease (ESRD) is driven by a different set of processes than in the general population. These processes lead to pathological changes in cardiac structure and function that include the development of left ventricular hypertrophy and left ventricular dilatation and the development of myocardial fibrosis. Reduction in left ventricular hypertrophy has been the established goal of many interventional trials in patients with chronic kidney disease, but a recent systematic review has questioned whether reduction of left ventricular hypertrophy improves cardiovascular mortality as previously thought. The development of novel imaging biomarkers that link to cardiovascular outcomes and that are specific to the disease processes in ESRD is therefore required. Postmortem studies of patients with ESRD on hemodialysis have shown that the extent of myocardial fibrosis is strongly linked to cardiovascular death and accurate imaging of myocardial fibrosis would be an attractive target as an imaging biomarker. In this article we will discuss the current imaging methods available to measure myocardial fibrosis in patients with ESRD, the reliability of the techniques, specific challenges and important limitations in patients with ESRD, and how to further develop the techniques we have so they are sufficiently robust for use in future clinical trials.  Patients with end-stage renal disease (ESRD) are at significantly increased risk of cardiovascular death compared to age-matched peers . The US Reactive interstitial fibrosis is commonly described in patients with hypertension and diabetes mellitus as a result of activation of the B-adrenergic system and renin-angiotensin-aldosterone system. Stimulated myofibroblasts increase collagen production and deposition in the ECM. It is also present in conditions such as dilated cardiomyopathy and states of pressure overload such as aortic stenosis .Infiltrative interstitial fibrosis is less common and characterized by deposition of insoluble substances such as protein tangles in amyloidosis or glycosphingolipids in patients with Fabry's disease.Replacement fibrosis is scarring that occurs after cardiomyocyte damage or once myocardial cell integrity has been affected. The fibrosis may be localised in conditions such as ischemic cardiomyopathy  affecting a particular coronary territory or a more diffuse distribution of fibrosis as seen in patients with dilated cardiomyopathy .It has been shown in a number of diseases that increased amounts of MF correlate strongly with the development of arrhythmias and heart failure and sudden cardiac death (SCD) –12; it iThe development of MF in patients with ESRD is complex . ArteriaThe development of DMF and its progression to replacement (scar) fibrosis occur as a continuum. Whilst replacement scar is irreversible, DMF is reversible as it occurs earlier in the disease process. Imaging techniques that allow safe, reliable, early detection of MF may improve disease risk stratification, be an important imaging biomarker in clinical research studies, and allow early treatment to prevent/slow progression to replacement fibrosis or even reverse it.Some strategies that have targeted LVH reduction in dialysis patients have been shown to reduce SCD and CV morbidity and mortality . There iImaging and Myocardial Fibrosis in Patients with ESRD. Identification of MF is historically done with endomyocardial biopsy. Endomyocardial biopsy is prone not only to sampling error but also to significant morbidity and mortality associated with the procedure itself [e itself , 31. We e itself  and doese itself . Howevere itself  and deliWhen imaged by ultrasound, natural acoustic reflections or “speckles” are identified in myocardial tissue . These sr = 0.88 and 0.81, resp.; p < 0.01) [The theory behind the relationship between strain, strain rate, and fibrosis is that fibrosis causes hypokinesia of the tissue in affected regions thereby reducing the amount of myocardial wall deformation which results in reduced (less negative) strain values , a theor < 0.01) .p < 0.0001). Pirat et al. used STE to compare the strain values of patients on HD, renal transplant recipients, and control subjects matched for age and sex, excluding patients with clinical coronary artery disease. All groups had similar ejection fractions, but average GLS was, again, significantly reduced in HD patients compared to renal transplant recipients, who similarly had impaired GLS in comparison to control subjects  [p < 0.001) [Key studies that have used STE in patients with ESRD are shown in < 0.001) . They al< 0.001) . Chen et< 0.001) . These sSeveral studies have looked at STE strain analysis in patients with advanced CKD  compared to matched HD patients –46. Thesp = 0.003), followed by circumferential strain  and lowest in radial strain . Interobserver analyses of longitudinal strain showed best reproducibility , followed by circumferential strain  and the least consistent measurements in radial strain . The use of radial strain should be discouraged due to its poor observer variability. It must also be noted that this study was conducted in healthy control subjects, and the reproducibility of these measures in ESRD patients is likely to be higher, especially given the variability in volume status.A study by Leischik et al. assessed the observer variability of radial, circumferential, and longitudinal strain in 21 healthy controls . LongituGayat et al. assessed the agreement of 3D-STE between different vendor software applications in patients with normal LV-systolic function. They found that intertechnique agreement between measures of radial, longitudinal, and circumferential strain was poor with intraclass correlation coefficient < 0.4 . This diIntegrated backscatter (IB) is a measure of the ultrasonic reflectivity of a selected part of myocardium, usually the posterior wall. Calibrated integrated backscatter (cIB) uses an intrinsic material such as pericardium  or blood (which appears darker) as a frame of reference to compare the reflectivity of myocardium  Figure .p < 0.01) and that high cIB associated with increased fibrosis in the biopsy specimen of heart tissue  [r = 0.55, p < 0.05) [r = 0.92) and interobserver (r = 0.88) reproducibility [Animal studies have demonstrated strong associations between cIB and histologically confirmed levels of MF, with higher IB values associated with the presence of fibrosis , 54. IB or wall) . Picano  < 0.05) . However < 0.05) . This stcibility .p < 0.01 for all groups) [p = 0.025) and that IB was an independent predictor of diastolic dysfunction  [Studies that have used IB in HD patients are summarised in  groups) . Althoug = 0.04) . Further = 0.04) . They shThese studies did not assess the correlation between cIB and histological presence of fibrosis in patients with ESRD. Whilst the inter- and intraobserver variability of cIB appear to be good, test-retest reproducibility has not been established and the correlation coefficients described between cIB and histologically proven fibrosis in other disease states are not consistent or as closely matched as necessary for an imaging biomarker.There are limitations to the use of echocardiography for the assessment of MF common to both STE and IB techniques. Measurement of IB and STE by echocardiography is dependent on image quality which varies depending on patient and operator related factors. In the studies of patients with ESRD described above, between 4 and 16.9% of subjects had echocardiographic data excluded due to poor image quality , 44, 61.CMR is the gold standard in cardiac imaging, with excellent intra- and interobserver variability for assessment of LV volumes and mass . SeveralUnfortunately, CMR-LGE and ECV quantification are not possible in patients with ESRD (or CKD 3–5) due to the risk of Nephrogenic Systemic Fibrosis (NSF) from GBAs –82. As lNative T1 mapping is a novel noncontrast CMR technique that enhances tissue characterization with CMR. T1 relaxation time is dependent on the molecular environment of water molecules within a given tissue. Native T1 signal can be affected by a number of different factors and T1 mapping characterizes different tissue compositions with great specificity . MyocardThere are a number of different pulse sequences that can be used to measure myocardial native T1 time, the modified look-locker inversion (MOLLI) recovery sequence and the shortened modified look-locker inversion (shMOLLI) recovery sequence being two examplesp < 0.001) and there was significant correlation between T1 values and histological fibrosis content (determined by collagen volume fraction) from endomyocardial biopsy  [p < 0.001). They identified that raised T1 values in amyloidosis patients correlated with systolic and diastolic dysfunction. There was no histological component to this study however, and it is likely that myocardial amyloid protein deposition causes raised native T1 times in these patients. Further work is needed to determine whether there is an absolute native T1 time cut-off or identification of patterns that differentiate amyloid from MF.Native T1 mapping has been shown to be a useful imaging biomarker in a number of disease states . Bull et= 0.002) . Similar= 0.002) . They foThe potential benefits of T1 mapping in patients with ESRD to define MF are clear . Currentp = 0.025) [r = 0.452, p = 0.008) and that septal T1 values correlate with predialysis highly sensitive Troponin-T  [p < 0.01). Furthermore we found that native T1 times were significantly higher in the interventricular septum of HD patients, compared to nonseptal myocardium (1292.7 ms (1258.9–1310.4) versus 1252.3 (1219.2–1269.6), p = 0.002) a difference not present in control patients. Significant correlations were also described between GCS, GLS (measured with CMR), and native T1 values  [p < 0.05) [r = 0.22, p < 0.05). The interstudy and interobserver reproducibility of native T1 mapping also appear to be extremely good with coefficients of variation of 0.7% and 0.3%, respectively [Rutherford et al. showed that native T1 times in 33 HD patients were significantly higher than 28 age- and sex-matched control subjects imaged at 3 T  . The sam= 0.027) . These f < 0.05) . The stuectively . Furtherectively .p = 0.001). They also showed the reproducibility of T1-rho mapping was very good, with interobserver intraclass correlation coefficient (ICC) of 0.966, intraobserver ICC of 0.937 for two readers, and test-retest interstudy ICC of 0.836 for the volunteer subjects.Wang et al. reported a study of HD patients that whilst native T1 times at 3 T were significantly higher than the established normal range  (1273.4 Studies are needed that correlate native T1 mapping with histological specimens from patients with ESRD to demonstrate unequivocally that increased T1 values are due to myocardial fibrosis and not myocardial oedema from fluid overload or any other disease processes.Whilst CMR is regarded as the gold standard for noninvasive assessment of cardiac structure and function, it is not without limitations. CMR is costly and not widely available and considerable skill is required for image acquisition and analysis. Furthermore postprocessing and analysis of scans can be time-consuming and may require bespoke software applications that are expensive. Additionally there will always be a subset of patients who are unable to undergo CMR scanning due to claustrophobia, metallic implants, or inability to lie flat.In 2011, Sado et al. reviewed the imaging techniques to define DMF, including the modalities we have discussed, and laid out a framework for technique development . They coEchocardiography has limited accuracy and reproducibility in defining geometric parameters and indices of systolic and diastolic function. This is especially true for HD patients who are subject to changes in cardiac filling from fluid status; LV mass and cavity size may be overestimated in up to 50% of dialysis patients . Whilst Although modern, more stable, macrocyclic GBAs are now available, which are potentially less toxic , it is uWhilst imaging biomarkers of MF are attractive measures for future interventional RCTs, we first need more robust and complete data on the relationship between the markers and their relationship to hard outcomes.