Nevertheless, during both regular pacing and extrasystolic excitation, the increased QT interval invariably remained shorter than the duration of mechanical systole, thus yielding positive EM window values. Hypokalemia-induced arrhythmogenicity was associated with slowed ventricular conduction, and shortened effective refractory periods, which translated to a reduced excitation wavelength index. Hypokalemia also evoked non-uniform prolongation of action potential duration in distinct epicardial regions, which resulted in increased spatial variability in the repolarization time. These findings suggest that arrhythmogenic effects of hypokalemia are not accounted for by the negative EM window, and are rather attributed to abnormal changes in ventricular conduction times, refractoriness, excitation wavelength, and spatial repolarization gradients.Normal hearts exhibit a positive time difference between the end of ventricular contraction and the end of QT interval, which is referred to as the electromechanical (EM) window. Drug-induced prolongation of repolarization may lead to the negative EM window, which was proposed to be a novel proarrhythmic marker. This study examined whether abnormal changes in the EM window may account for arrhythmogenic effects produced by hypokalemia. Left ventricular pressure, electrocardiogram, and epicardial monophasic action potentials were recorded in perfused hearts from guinea-pig and rabbit. Hypokalemia (2.5 mM K In healthy human subjects, the duration of mechanical systole is greater than the duration of ventricular repolarization, thus contributing to the positive EM window + concentrations, which represents a side effect of diuretic therapy. Hypokalemia provokes QT interval lengthening, and markedly increases arrhythmogenic risks in cardiac patients Cardiovascular disease is often associated with reduced serum KThis study complies with the European Community Guidelines for the Care and Use of Experimental Animals, and was approved by the Animal Ethics Screening Committee of the Panum Institute (clearance number: 2010/561-1799). Female Dunkin-Hartley guinea-pigs  and female New Zealand white rabbits  were allowed to acclimate to the housing conditions, with free access to food and tap water, for at least 7 days prior to entry into the study.2 and 5%CO2. During control normokalemic perfusions, the perfusion solution contained (in mM) 118.0 NaCl; 4.7 KCl; 2.5 CaCl2; 25 NaHCO3; 1.2 KH2PO4; 1.2 MgSO4; and 10.0 glucose, and had a pH of 7.4. Hypokalemic perfusions were accomplished using 2.5 mM K+-containing solution.The experiments on isolated, perfused hearts were performed as described previously The Langendorff perfusion set-up was equipped with two ISOTEC pressure transducers  to measure aortic pressure and left ventricular (LV) developed pressure. The aortic pressure transducer was connected to the aorta block of the set-up. The ventricular pressure transducer was coupled to the balloon-tipped catheter introduced into the LV cavity via an incision made in the left atrium. The volume of the LV balloon was adjusted to yield an end-diastolic pressure of 0–5 mm Hg. LV developed pressure was calculated as the difference between end-systolic and end-diastolic pressure. The coronary flow rate was determined using an ultrasonic flowmeter probe  placed just above the aortic cannula. The electrical activity of the heart preparations was assessed from the volume-conducted ECG as well as monophasic action potential recordings.Throughout the experiments, the heart preparations were kept immersed in the temperature-controlled, perfusate-filled chamber to minimize thermal loss. LV developed pressure, aortic pressure, coronary flow rate, ECG and ventricular monophasic action potentials were continuously monitored using a 16-channel PowerLab system .1–S1 interval: guinea-pig = 250 ms, rabbit = 350 ms) using 2 ms rectangular pulses of twice the diastolic threshold current generated by a programmable stimulator . A premature extrastimulus (S2) was delivered at 10 s intervals to the pacing site, progressively reducing the S1–S2 coupling interval in 5–10 ms steps from 150 ms until the preparation failed to respond to S2. The effective refractory period was defined as the longest S1–S2 interval producing no extrasystolic response.Previous works suggest that hypokalemia predominantly increases VT inducibility in the LV rather than the RV chamber 90). The local activation times were measured at the LV and RV MAP recording sites as the intervals between the pacing stimulus and the fastest upstroke of the following action potential. Ventricular repolarization time was found as the sum of the activation time and the corresponding APD90 value. Transepicardial variability of repolarization time was assessed by calculating the standard deviation of the mean repolarization time value determined from six MAP recording sites.Monophasic action potentials (MAP) were recorded using three LV and three RV pressure contact electrodes applied to the basal epicardial surface . The MAPDuring LV epicardial pacing, the LV-to-RV conduction time was determined as the difference between the mean RV and LV activation times, which were obtained from three MAP recording sites within each ventricular chamber. The excitation wavelength index was calculated as a ratio of effective refractory period and the LV-to-RV conduction time end interval; end interval and the QT interval on ECG, as described previously The duration of electromechanical systole was assessed by measuring the interval between the Q wave on ECG and the end of ventricular contraction on the LV pressure signal (Q-P2-evoked) beat. The S2-evoked values were measured following extrasystolic stimulation applied at the shortest coupling stimulation interval that was either preceding refractoriness or preceding VT development .In total, 17 isolated, perfused heart preparations were used in this study, in order to assess electrophysiological effects produced by hypokalemia in guinea-pig (n = 10) and rabbit (n = 7) ventricles. The experiments were started with 30 min control normokalemic perfusion, followed by measurements of basal variables, and then switching to 30 min hypokalemic perfusion. During programmed stimulation, the electrophysiological parameters were determined in the last regular beat prior to extrastimulus application, and compared to those measured in the premature , LV developed pressure , and coronary flow rate .In spontaneously beating heart preparations, hypokalemia had no effect on cardiac beating rate , and in 5 out of 7 (71%) rabbit heart preparations (P = 0.02) exposed to hypokalemia  was found to induce torsade de pointes in 8 out of 10 (80%) hypokalemic guinea-pig hearts (P = 0.0007), and in 5 out of 7 (71%) rabbit hearts (P = 0.02). In guinea-pig hearts, the episodes of torsade de pointes were short-lasting (0.5–2.0 s) and self-terminating. In rabbits, the tachyarrhythmia precipitated into sustained ventricular fibrillation in 3 out of 5 (60%) heart preparations with inducible torsade de pointes.No episodes of spontaneous or programmed stimulation-evoked VT were observed during control normokalemic perfusion. Nevertheless, arrhythmic susceptibility was markedly increased during hypokalemia. Multiple ventricular ectopic beats were recorded during 30 min hypokalemic perfusion, both in guinea-pig and rabbit hearts. The short runs of monomorphic VT were observed in 7 out of 10 (70%) guinea-pig heart preparations , but increased the mean RV activation time . Consequently, the LV-to-RV conduction time was increased upon hypokalemic perfusion from 5.9±0.5 ms to 7.6±0.6 ms (P = 0.03) in guinea-pig hearts, and from 13.7±1.5 ms to 16.6±1.6 ms (P = 0.04) in rabbit hearts.In SP = 0.01) and rabbits .Effective refractory periods were reduced in hypokalemic heart preparations from guinea-pig  and rabbit hearts .Reduced effective refractory periods in association with prolonged LV-to-RV conduction times contributed to decreased values of the excitation wavelength index in guinea-pig hearts  determined at individual epicardial recording sites.1–S1 pacing was found to be 120±2 ms in guinea-pig hearts, and 148±5 ms in rabbit hearts. The standard deviation of the mean repolarization time value was 6.9±0.4 ms in guinea-pig hearts, and 13.9±1.0 ms in rabbit hearts. In both animal species, transepicardial variability in repolarization time was attributed to longer action potential duration in the RV compared to the LV chamber , and to later RV than LV activation upon LV epicardial pacing . Extrasystolic stimulations were associated with conduction slowing, as evidenced by increased activation time in S2- as compared to S1-evoked beats, and shortened APD90 (the restitution effect) in guinea-pig hearts  and extrasystolic stimulation . Throughout the ventricular epicardium, the prolongation of repolarization time was highly non-uniform. For example, in hypokalemic guinea-pig hearts, the minimal effect on repolarization time  was produced in the LV lateral wall  was evoked in the RV lateral wall (site 3 in P = 0.01) and extrasystolic stimulation .In hypokalemic hearts, the mean repolarization time value from six epicardial recording sites was increased during both regular pacing  was elicited in the LV lateral wall  was determined in the RV posterior wall (site 1 in P = 0.02) and extrasystolic stimulation .Non-uniform changes in repolarization time have also been observed in hypokalemic rabbit hearts, wherein the minimal effect  appears to be a clinically relevant phenomenon, which has been observed in different cardiovascular conditions including mitral leaflet prolapse + current  was combined with β-adrenoreceptor agonist challenge . However, no attempts have been previously made to examine whether the mismatch between the duration of electrical and mechanical systole may contribute to arrhythmic substrate in the setting of hypokalemia, the most common electrolyte abnormality seen in cardiac patients The role of the negative EM window in the mechanism of drug-induced proarrhythmia was nevertheless challenged in study by Laursen et al. (2011) + levels were associated with increased mortality in cardiac patients The ALLHAT trial showed that hypokalemia may be found in 13% of hypertensive patients treated with diuretics + currents such as IKr, the rapid component of the delayed rectifier, and IK1, the inward rectifier 2+ handling via mechanisms related to inhibition of Na+-K+ pump and subsequent stimulation of the reversed mode of the Na+-Ca2+ exchange Importantly, hypokalemia-induced arrhythmogenicity may potentially be linked to the reverse relationships between the QT interval and mechanical systole. First, hypokalemia has been shown to reduce the magnitude of repolarizing K+ channels from inactivation. In support of this argument, the recurrence of excitability during the repolarization phase was found to occur at less negative membrane potentials in hypokalemic guinea-pig papillary muscle, and this effect was abolished by Na+ channel blocker The excitation wavelength refers to the distance travelled by the depolarization wavefront during the refractory period Reduced effective refractory period, in association with prolonged interventricular conduction time, contributed to a decreased value of the excitation wavelength index in hypokalemic guinea-pig and rabbit hearts in the present study. This change may set a stage for tachyarrhythmia, because a reduced excitation wavelength allows re-entry within a smaller mass of cardiac tissue to be sustained + currents are variable throughout the ventricular epicardium 90 values measured on steady-state pacing were found to be greater in RV compared to the LV chamber both in guinea-pig and rabbit hearts. Importantly, spatial heterogeneities in the distribution of K+ currents may also contribute to the dissimilar prolongation of repolarization at distinct myocardial regions, as observed in the present study  would be associated with greater occurrence and duration of cardiac arrhythmias in human patients, as compared to those reported in the present study.The size of the guinea-pig and rabbit hearts is much smaller than the human heart, meaning that the ability to sustain re-entrant cardiac arrhythmia is less in these animal species. This difference may imply that the same degree of hypokalemia  epicardium (solid circles in panels A and C) and the right ventricular (RV) epicardium (open circles in panels B and C). Panel C shows that in each ventricular chamber, the electrodes were placed in anterior ventricular wall (AW), lateral ventricular wall (LW), and posterior ventricular wall (PW). LAD is the left anterior descending coronary artery.(PDF)Click here for additional data file.


Left ventricular rotational deformation, which arises from contraction of myofibers arranged in a helical structure, plays a crucial role in cardiac mechanics. Myocardial dysfunction in cardiomyopathies is usually associated with altered diastolic rotation -3. HowevLV tagging in a dense radial pattern was performed at the mid LV short axis level in twelve healthy subjects and nine cardiomyopathic patients at 1.5T or 3.0T. Number of radial taglines was set to 22 per circle. Corresponding short axis cine images were available in all subjects. The mid LV short axis was divided into 6 circumferential segments according to the AHA 17-segment model. To compute rotation of each specific segment, the tag points located on the segment were automatically detected and traced through successive frames. Finally, the rotation of each LV sector was estimated using the spatial coordinate of the tag points plus that of the LV center of mass.The resulting mid ventricular rotation values and rotation rates in myopathic patients were decreased relative to healthy subjects in most circumferential segments table . MoreoveInitial results with high density radial tagging suggest a heterogeneous and diminished pattern of regional rotation in patients with cardiomyopathy. This may potentially reflect an imbalance in LV mechanical function and lead to decreased global rotation. Regional heterogeneity of rotation may merit further study as a myocardial functional marker. The simple and rapid calculation of regional rotation supported by radial tagging provides a unique advantage to study this parameter.Images were obtained through DCVI section at UCLA.


Sepsis-induced myocardial dysfunction is a well-recognized condition and confers worse outcomes in septic patients. Echocardiographic assessment by conventional parameters such as left ventricular ejection fraction (LVEF) is often affected by ongoing changes in preload and afterload conditions. Novel echocardiographic technologies such as speckle tracking echocardiography (STE) have evolved for direct assessment of the myocardial function. We investigate the measurement of myocardial strain by speckle tracking echocardiography for the diagnosis of sepsis-induced myocardial dysfunction.This is a case-control study at a university-affiliated medical intensive care unit. Consecutive adult medical patients admitted with a diagnosis of septic shock were included. Patients with other causes of myocardial dysfunction were excluded. They were compared to age-matched, gender-matched, and cardiovascular risk-factor-matched controls, who were admitted to hospital for sepsis but did not develop septic shock. Transthoracic echocardiography was performed on all patients within 24 hours of diagnosis, and a reassessment echocardiogram was performed in the study group of patients upon recovery.n = 33) (study group) and 29 matched patients with sepsis but no septic shock (control group) were recruited. The mean sequential organ failure assessment (SOFA) score for the study and control groups were 10.2 and 1.6, respectively (P < 0.001). In patients with septic shock, the mean arterial pressure was lower , and the heart rate was higher . The cardiac output  and systemic vascular resistance  were similar. The study group had a greater degree of myocardial dysfunction measured by global longitudinal strain (GLS) , and the myocardial strain differed upon diagnosis and recovery . Conventional echocardiographic measurements such as LVEF  did not differ between the two groups.Patients with septic shock (Speckle tracking echocardiography can detect significant left ventricular impairment in patients with septic shock, which was not otherwise detectable by conventional echocardiography. The reversible nature of myocardial dysfunction in sepsis was also demonstrable. This echocardiographic technique is useful in the diagnosis and monitoring of sepsis-induced myocardial dysfunction. Sepsis is one of the commonest conditions necessitating patient admission to the intensive care unit, and is associated with a myriad of organ dysfunctions. Sepsis-induced myocardial depression, or septic cardiomyopathy, is a well-recognized organ-specific manifestation in sepsis. The condition refers to depressed myocardial function during sepsis, which is fully reversible upon recovery. Septic cardiomyopathy was first described in 1984 by Parker et al, using the technique of radionuclide ventriculography, showing a significant incidence of impaired left ventricular ejection fraction (LVEF) of less than 40 % in patients with septic shock [Two-dimensional transthoracic echocardiography is nowadays one of the first line investigations in patients with septic shock because of its accessibility and non-invasive nature. It is useful in ruling out other causes of hypotension such as cardiogenic and obstructive shock. In sepsis, however, assessment of myocardial function by conventional echocardiographic parameters such as left ventricular ejection fraction (LVEF) is affected to a large degree by ongoing changes in preload and afterload conditions. Other methods of quantifying the left and right ventricular function, such as the use of Doppler-derived indices in the calculation of the myocardial performance index (MPI) , and theSpeckle tracking echocardiography (STE) was first described in 2004 as a method of non-Doppler-based and angle-independent measurement of left ventricular function , 6. BaseIn this study, we piloted the application of speckle tracking echocardiography in sepsis-induced myocardial dysfunction. We investigated the measurement of myocardial strain to describe the incidence and clinical progression of this clinical entity. We hypothesized that myocardial depression, measured by STE, is present in intensive care patients with septic shock, and is reversible upon recovery.This is a single center, case-control study conducted at a university-affiliated tertiary care adult intensive care unit. The study protocol  reference number: UW 13-592) was approved by the IRB of The University of Hong Kong (HKU) and Hospital Authority Hong Kong West Cluster (HA HKW). Written informed consent was provided by all patients, and if the patient's fitness to consent was impaired at the time of recruitment, written consent was obtained from the patient’s next of kin.Definitions laid out by the International Sepsis Definition Conference  were adoConsecutive adult medical patients admitted to the intensive care unit were screened and recruited (study group) if they met the following criteria: (1) were aged 18 years or older, (2) had clinical symptoms suggestive of sepsis, and (3) developed septic shock requiring the use of inotropes or vasopressors. They were compared to a group of age-matched, gender-matched and cardiovascular risk-factor-matched controls (control group), who were admitted to hospital for sepsis but did not develop septic shock.Patients were excluded if they met one of the following criteria: (1) active diagnoses directly relating to myocardial dysfunction, such as acute myocardial infarction, myocarditis, unstable arrhythmia, and post-cardiopulmonary resuscitation status; (2) significant underlying cardiac conditions, such as congenital heart disease, valvular heart disease, and cardiomyopathy; (3) informed consent could not be obtained; and (4) rapid clinical deterioration did not permit timely completion of the echocardiograms.Two serial transthoracic echocardiographic examinations were performed in the study group of patients, the first within 24 hours of admission to the intensive care unit, and then 72 hours thereafter or at the time of recovery, whichever was earlier. The time of recovery was defined as the time when the patient was weaned off all inotropic or vasopressor support. For the control group of patients, a one-time transthoracic echocardiography was performed within 24 hours of diagnosis of sepsis.Bedside two-dimensional transthoracic echocardiography was performed using a commercially available system, the General Electric Healthcare Vivid q cardiovascular ultrasound system. All examinations were performed by a single operator – a certified critical care specialist with interest in hemodynamics and echocardiography, under the supervision of a certified cardiologist. Echocardiography was performed with the patient in the supine or left lateral position. Images were obtained using a 3.5-MHz ultrasound transducer probe and stored digitally in cine-loop format.Standard echocardiographic measurements were obtained according to current recommendations by the American Society of Echocardiography , 12. StaCardiac output was calculated by the velocity time integral (VTI) measured by Doppler echocardiography at the left ventricular outflow tract (LVOT). The cardiac preload was represented by right atrial pressure, estimated by inferior vena cava (IVC) diameter and the presence of inspiratory collapse. The cardiac afterload, namely systemic vascular resistance, was calculated as the difference between the mean arterial pressure and central venous pressure  divided by the cardiac output.Two-dimensional speckle tracking echocardiography (STE) was assessed along the longitudinal coordinate of the left ventricle. The left ventricular global longitudinal strain (GLS) was obtained by averaging values obtained in the longitudinal three-chamber, two-chamber, and four-chamber planes in accordance with current guidelines . Strain U test or Student t test. All tests of significance were two-tailed and a P value of 0.05 was considered to be statistically significant.Results were analyzed with SPSS Statistics version 21 for Mac (IBM Corp). We report the number and percentage for categorical variables, and the mean and standard deviation for continuous variables with normal distribution. Categorical variables were compared using the Fisher exact test or Pearson chi-square test, and continuous variables were compared using the Mann-Whitney From 1 January 2014 through 31 January 2015, 68 consecutive adult medical patients were admitted to the intensive care unit with a diagnosis of septic shock and considered for selection: 16 patients were excluded due to active cardiac conditions, 13 patients were excluded based on preexisting cardiac abnormalities, 4 patients had rapid clinical deterioration and died before complete echocardiographic examination was possible. One patient was excluded because informed consent could not be obtained, and one patient was excluded during echocardiographic data processing due to unsatisfactory image quality. Details of the excluded patients are given in Fig. The control group were recruited retrospectively, and consisted of 30 patients who were admitted to the medical ward with sepsis but did not develop septic shock. One patient was excluded due to unsatisfactory echocardiographic image quality.P < 0.001), higher incidence of bacteremia , and greater need for renal replacement therapy  and mechanical ventilation . The mean SOFA score for the study and control groups was 10.2 and 1.6 respectively (P < 0.001).Key clinical characteristics of the patients recruited into the study are shown in Table n = 6), and the 90-day all-cause mortality rate was 41.9 % (n = 13). There were no deaths in the control group . Amongst the 33 patients in the study group, the 30-day all-cause mortality rate was 18.2 % (P = 0.032), and a higher heart rate . Measured by echocardiography, the study and control groups had a similar mean stroke volume , mean cardiac output , and mean cardiac index  . The afterload was similar .The cardiac preload, represented by right atrial pressure, was higher in the study group , fractional shortening (FS) , and left ventricular index of myocardial performance (LIMP)   , two-chamber , and four-chamber measurements   , there was a significant improvement in left ventricular strain upon recovery . In nonsurvivors, this difference in GLS was not detected  (Table On comparing the first and second echocardiographic examinations in the study group who could be weaned off vasopressors or inotropes (P < 0.001) between the two groups of patients. The strain value of –18.3 % in our control group is comparable to the previously reported range of –17 % to –23 % in normal healthy subjects [P < 0.001). Again, there was no significant difference in LVEF and FS between the two groups of patients.This is one of the first case-control studies to apply the relatively novel technology of STE in the diagnosis and monitoring of sepsis-induced myocardial depression in the adult population. There are two important conclusions. The first part of our study involved comparing the strain values in patients with septic shock and patients with sepsis only. We observed a significant difference in the measured GLS , by a negligible absolute value of 1.5 mmHg, evidencing that these patients with hypotension have been adequately volume-resuscitated prior to echocardiographic analysis. All patients in the study group were instituted on vasopressors, with comparable afterload indices between the two groups .Recent research has provided preliminary data indicating that strain may be sensitive to acute changes in load . We undeP = 0.026). Nonsurvivors did not exhibit the improvement in myocardial strain at 72 hours . This supports the current understanding of septic cardiomyopathy as a reversible form of myocardial impairment during the sepsis syndrome.The second part of this study involved serial echocardiographic examinations in the group of patients with septic shock. In the patients who could be weaned off vasopressors by 72 hours, we observed a difference in strain values obtained at diagnosis and recovery (–14.6 % vs –16.0 %, The diagnosis of sepsis-induced myocardial impairment has been difficult without the availability of a sensitive and specific bedside diagnostic tool. One of the commonest measures of left ventricular function, LVEF, is affected to a significant degree by the changing preload and afterload in sepsis. Vieillard-Baron, in a series of echocardiography studies, showed that when performed at different times after the onset of septic shock, echocardiography yields different incidences of left ventricular dysfunction , 18. In STE has emerged as a direct, angle-independent, and highly reproducible measurement of left ventricular function. Its application in conditions such as heart failure with preserved ejection fraction  has showWe managed to show how STE may be useful as a tool for diagnosis as well as disease monitoring in sepsis-induced myocardial impairment. It enables the detection of subtle left ventricular dysfunction early in the course of illness, which is not otherwise detected by measurement of LVEF alone, and further discriminates the reversibility of this condition in patients who subsequently recover. In demonstrating similar preload and afterload parameters in our study and control groups, we have eliminated possible interference by these factors in the measurement of strain. The proper identification and description of sepsis-induced myocardial impairment may have important therapeutic implications, guiding the use of cardioprotective strategies such as β-blockers in the management of patients with septic shock .Our study has several limitations. First, the sample size was small, especially in the subgroup analyses. Second, as the timing of the reassessment echocardiogram as either when the patient came off inotropic or vasopressor support, or at 72 hours, was decided arbitrarily, we were unable to prove the complete reversibility of strain measurements to normal values upon recovery. Third, we did not have a resuscitation protocol for the choice and dose of inotropes and vasopressors. Finally, our data were not compared to more objective modalities of quantifying ventricular function, such as cardiovascular magnetic resonance imaging or radionuclide ventriculography.In conclusion, sepsis-induced myocardial impairment can be detected by left ventricular global longitudinal strain measured by speckle tracking echocardiography in patients with septic shock, and this was not otherwise identifiable by conventional echocardiographic parameters. Strain measurement, which can now be performed at the beside, is useful for the diagnosis and monitoring of this disease. Further studies are needed to define cutoff values and evaluate its application as a potential diagnostic tool for sepsis-induced myocardial depression.Strain measurements are more sensitive than conventional echocardiographic parameters in detecting sepsis-induced myocardial impairment.Patients with septic shock have a greater degree of myocardial impairment compared to patients with sepsis only.Strain measurements can feasibly be performed at the bedside and can be used for serial monitoring of sepsis-induced myocardial impairment.


Several studies have demonstrated that uremic patients who have preserved left ventricular ejection fraction (LVEF) could still have the potential for systolic dysfunction. The aim of this study was to assess the differences between the left ventricular (LV) myocardial function in hemodialysis and nondialysis uremic patients based on three-dimensional speckle-tracking echocardiography.The study population consisted of 35 maintenance hemodialysis patients , 30 uremic patients who were hospitalized for the creation of a primary arteriovenous fistula , and 32 healthy volunteers. All of the patients had normal left ventricular ejection fractions . Three-dimensional speckle tracking echocardiography was performed to assess the left ventricle's global three-dimensional strain, regional longitudinal strain, circumferential strain, and radial strain.P<0.001). However, the three-dimensional strain and the regional longitudinal strain were lower in the hemodialysis patients than in the controls (P<0.01). In the hemodialysis patients and the control group, the longitudinal strain, circumferential strain, and radial strain were higher at the apical level than they were at the basal level and midlevels. A multivariate linear regression analysis showed that the blood urea nitrogen and creatinine levels were independently associated with the values of the global three-dimensional strain  and the longitudinal strain .The left ventricular regional longitudinal strain, radial strain, circumferential strain, and global three-dimensional strain were significantly decreased in the nondialysis patients compared with the other two groups (all, Three-dimensional speckle-tracking echocardiography may detect myocardial dysfunction in patients with uremia who have preserved LVEF. The global three-dimensional strain and the regional longitudinal strain appear to be superior in hemodialysis patients compared with nondialysis patients. Uremia is associated with an increased risk of cardiovascular diseases, including coronary artery disease, myocardial infarction, and heart failure. Mortality is increased by 10- to 20-fold in dialysis patients compared with healthy individuals Three-dimensional speckle-tracking echocardiography (3D STE) is a new and emerging technique. It relies on 3D echocardiographic datasets and tracks the motion of speckles within a scanned volume, irrespective of direction. Yu et al. demonstrated that the 3D strain (3DS), which is best described as the “principle tangential strain,” may display the resulting direction's muscle fiber contractions, which are aligned either parallel to or tangential to the myocardial surface Between August 2012 and June 2013, 75 uremic patients with a LVEF of 55% or greater were consecutively enrolled from the nephrology clinic. The cases excluded from the study were 2 patients with arrhythmias, 2 patients with severe valvular disease, 3 patients with uncontrolled hypertension , and 3 patients for whom the 3D STE image quality was inadequate. Finally, 65 patients with uremia were analyzed in this study. The uremia patients included 35 patients on maintenance hemodialysis  who were prescribed a standard dose of dialysis targeting an equilibrated dose (Kt/V of urea) of 1.2 or more and 30 patients who were hospitalized for the creation of a primary arteriovenous fistula . We recruited 32 age-matched control volunteers from among individuals who received routine checkups at our hospital who had normal results on electrocardiography, transthoracic echocardiography, multi-slice spiral computed tomography (CT), and coronary angiography and had normal blood pressure. The biochemical indexes of all of the study participants were evaluated at the hospital laboratory. The indexes included total cholesterol, glyceride, hemoglobin, creatinine, and urea nitrogen levels in the blood. Written and informed consent was obtained from all of the study participants. The study was approved by the local ethics committee of the Sir Run Run Shaw Hospital .All of the echocardiographic studies were performed using a commercial scanner . Real-time 3D echocardiographic imaging was performed from the cardiac apex by a fully sampled matrix-array transducer. The full-volume acquisition (which included 6 wedge-shaped volumes) was recorded with 6 consecutive cardiac cycles during a single breath-hold. Moreover, the temporal and spatial resolutions of the images were optimized by decreasing the depth and adjusting the sector width to ensure that the entire LV cavity was included within the pyramidal volume. An experienced echocardiographer obtained all of the echocardiographic images using a standard protocol, and another echocardiographer who was blinded to the clinical data of the study participants analyzed the images. An offline analysis of the data was performed using Tom-Tec 4.0 analysis software . For the tracing of the endocardium and epicardium, the following five views were displayed: (1) the apical four-chamber view; (2) the apical two-chamber view and the three short-axis views; (3) the apex of the LV; (4) the midlevel of the LV; and (5) the basal level of the LV. The LV epicardium and endocardium were traced automatically, and the tracings were refined with further adjustment. Thus, in a cardiac cycle, the software was able to perform both global and segmental strain analyses, including the global 3D strain (3DS), regional longitudinal strain (LS), radial strain (RS), and circumferential strain (CS). Meanwhile, the end-systolic and end-diastolic LV volumes and ejection fractions were observed automatically. On the parasternal long-axis view, the thickness of the interventricular septum and LV posterior wall were measured at the end-diastole of the LV. The LV diameters were measured at the end-systole and end-diastole phases. The early (E) and late (A) diastolic peak velocities of the mitral inflow and the early (E′) and late (A′) diastolic peak velocities of the septal mitral annulus were measured by pulse wave Doppler and Doppler tissue imaging. Subsequently, the E/A ratio, E′/A′ ratio, and E/E′ ratio were calculated to evaluate the diastolic function of the LV.For the intraobserver reproducibility, 10 subjects were analyzed twice within 4 weeks by one investigator, and the mean values of 16 segments at three levels of LV for RS, CS, LS and 3DS were calculated. The interobserver reliability assessment was performed by analyzing 10 subjects who were chosen randomly by 2 independent investigators. Both observers were blinded to the previous measurements.2 tests. Independent determinations of subclinical myocardial systolic dysfunction in patients with uremia were examined using multivariate linear regression. The intraclass correlation coefficients (ICCs) method was used to assess the intraobserver reproducibility and the interobserver reliability for the values of the 3D global strain and regional strain. The ICCs were expressed as percentages. The clinical significance was categorized as follows: “excellent,” if the ICC was 0.80 or greater; “good,” if the ICC was between 0.61 and 0.79; “moderate,” if the ICC was between 0.41 and 0.60; and “poor,” if the ICC was 0.4 or less All statistical analyses were performed using SPSS version 16.0 software . All data were presented as the mean ± the standard deviation (SD). The duration of uremia and hypertension were presented as median values. Differences in the continuous data and categorical data between the patients and the controls were compared using a one-way analysis of variance and χP>0.05). However, the total cholesterol and glyceride levels were greater in the hemodialysis and nondialysis groups than in the control group . The total cholesterol and glyceride levels were not significantly different between the hemodialysis and the nondialysis groups. The hemoglobin level was lower in the nondialysis group than in the hemodialysis group and the control group . No difference was observed between the hemodialysis group and control group. The creatinine (CRE) and blood urea nitrogen (BUN) levels were significantly greater in the hemodialysis and nondialysis groups than in the control group . These two levels were significantly decreased in the hemodialysis group compared with the nondialysis group .The general clinical indexes and the blood indexes of the hemodialysis group, the nondialysis group, and the control group are summarized in P<0.01). However, there were no significant differences in these factors between the hemodialysis and nondialysis groups. The LVEF was similar in the three groups. Furthermore, the E, A, E/A ratio, E′, A′, and E′/A′ ratio  were decreased significantly only in the nondialysis group compared with the hemodialysis group and the control group. However, no difference was found between the hemodialysis group and the control group.The echocardiographic parameters of the study groups are shown in P<0.01) (P<0.01). In the CS and RS, there was no significant difference between the hemodialysis and the control group. The LS, CS, and RS were higher at the apical level than they were at the basal level and the midlevel in the hemodialysis patients and the control patients. However, these values were not significantly changed in the nondialysis group. Based on the multivariate linear regression analysis, the duration of the uremia, systolic blood pressure, LVST, E/E' ratio, and the levels of the total cholesterol, glyceride, Hb, CRE, and BUN were associated with the 3DS, LS, RS and CS, which were used to examine the risk factors for preclinical myocardial systolic dysfunction. The levels of CRE and BUN were independently associated with the 3DS value  and the LS value  (One hundred and sixty (10%) of 1552 segments were excluded from the 3D STE analysis because of drop-out. The 3D STE analyses of the three groups are shown in P<0.01) . In addi= 0.029) .The ICCs are shown in Cardiac function is still incompletely characterized in uremia patients. This is the first study to compare the differences in the global and regional myocardial functions in hemodialysis and nondialysis patients based on 3D STE. The primary findings of this study are as follows: (1) the global LV systolic function (EF) was normal in the uremic group; however, the global 3DS and the regional LS, RS, and CS were decreased in the nondialysis group, indicating that the LV regional long-axis, short-axis, and global functions were already impaired; (2) the 3DS and LS were higher in the hemodialysis group than in the nondialysis group, indicating that the LV global and regional long-axis functions were superior in the hemodialysis patients; and (3) the decreased CS and RS were observed only in the nondialysis patients and not in the hemodialysis patients. These results demonstrate that, in myocardial dysfunction, the global LV dysfunction and LV regional long-axis systolic dysfunction appear to be more vulnerable to change compared with the short-axis function.The LVEF reflects the sum of all of the regional shortening in the left ventricle, and regional wall motion impairment may not reduce the LVEF unless several segments are involved.In our study, the LVEF was normal in the uremia group; however, the LV regional long-axis, short-axis and global functions were already impaired in the uremia patients as assessed by 3D STE, regardless of whether they were undergoing hemodialysis. The underlying mechanisms of the decreased LV function in uremia patients are complex and not thoroughly understood. We speculated that hypertension, LV hypertrophy, LV remodeling, coronary artery disease, myocardial fibrosis, and apoptosis may contribute to LV dysfunction in uremia patients with preserved LVEF. In addition, we found that the LV global function and regional long-axis function were superior in the hemodialysis patients, as shown by the higher 3DS and LS in the hemodialysis group than in the nondialysis group. We believe that the improvement in the LV function in the hemodialysis patients may have resulted from factors such as improvements in their anemia, malnutrition, calcium-phosphorus metabolism disorder and acid-base balance, etc. These factors may decrease the volume load of the LV and thereby improve the anoxic condition of the tissues and organs. The increase in the myocardial oxygen and blood flow as well as the improvement in the LV remodeling may also promote LV systolic function. Therefore, the results from the current study indicate that the 3DS and LS may be sensitive predictors of preclinical LV dysfunction in patients with uremia, particularly in hemodialysis patients. The detection of subclinical myocardial dysfunction may assist clinical doctors in treating uremia patients earlier , and thereby reduce the incidence of cardiovascular disease while improving long-term outcomes.Yan et al. also demonstrated that the CS and RS decreased only in the nondialysis patients based on the 2D STE In addition, myocardial deformation occurs in three dimensions and can be characterized in the longitudinal direction, as well as in the circumferential and radial directions. Subepicardial fibers play a major role in both the RS and LS The LV's contractions travel from the apex to the basal region. Our study also found that the LS, CS, and RS were higher at the apical level than at the basal level and the midlevels in the control and hemodialysis groups. However, this phenomenon did not appear in the nondialysis group. A previous study has shown that myocardial contractility reflects the influence of preload 1 pathway may play a role in cardiac fibrosis. Lekawanvijit et al. showed that cardiac fibrosis is reversible by reducing the serum IS level in uremic rats A decreased myocardial strain in uremia patients reportedly results from LV hypertrophy rather than from uremic toxicity The temporal and spatial resolutions are relatively lower in the 3D STE than in the 2D STE. Therefore, several patients had to be excluded because the image quality in 1 or more segments was insufficient for the STE analysis. Moreover, our study included a relatively small number of patients. In addition, the long-term cardiovascular event rates or survival assessment in the patients on maintenance hemodialysis was not presented in this study.Three-dimensional STE analysis offers a useful tool for predicting the myocardial function of the LV in uremic patients. The global LV systolic function and the short-axis and long-axis regional LV myocardial function may be impaired in nondialysis patients who have preserved ejection fraction. However, the global LV function and regional LV systolic function appeared to be superior in the hemodialysis patients over those in the nondialysis patients. 3DS and LS may be sensitive predictors of LV global and regional systolic dysfunction.


Ventricular arrhythmias are a leading cause of non-elegibility to competitive sport. The failure to detect a significant organic substrate in the initial stage of screening does not preclude the identification of structural pathologies in the follow-up by using advanced imaging techniques.Here we report the case of a senior athlete judged not elegible because an arrhythmia with the morphology consistent with the origin of the left ventricle, in which subsequent execution of a cardiac MR and a thoracic CT scan has allowed the identification of an unique association between an area of myocardial damage, probable site of origine of the arrhythma, and a rare aortic malformation. Ventricular arrhythmias are a leading cause of non-elegibility to competitive sport.  As in thA 60-year-old male high-level tennisplayer was referred at our outpatient sports cardiology clinic for palpitations after competition. 24-hour Holter ECG recordings revelead frequent and complex ventricular arrhythmias with dominant right bundle branch block morphology .A complete diagnostic work-up, including echocardiogram, stress test, ventriculography and coronary angiogram, failed to detect any organic substrate of the arrhythmia. No tachicardia was inducible by ventricular stimulation performed with an aggressive protocol. However the athlete was judged not eligible for competition due to the high weight of arrhytmic events and high heart rate of ventricular tachycardia (R-R cycle of less than 400 msec on ECG). In the follow-up period a cardiac MRI was performed showing normal left and right ventricular cavity dimensions and systolic function on cine images. At the level of the interventricular septum, pre- and post-contrast morphological images detected a focal area of fibrofatty replacement involving the inferior interventricular junction . The samSubsequently a thoracic CT scan demonstrated the absence of esophageal and/or tracheal compression, confirming the absence of a ligamentum arteriosum to complete the vascular ring .A left-dominant variant of arrhythmogenic cardiomyopathy (LDAC) has been recently described  and it i“Chronic” myocarditis is also a possible cause of apparently idiopathic arrythmia of the athletes.  Cardiac In the present case, detection on MRI of patchy myocardial fibrosis with subepicardial/midwall distribution, for lack of a medical history and of genetic or biopsy evidences, can not be attributed with certainty to the LDAC nor the myocarditis.ligamentus arteriosus also persists a complete vascular ring can be generated, with consequent compression of the esophagus and trachea and need of corrective surgery. [The Kommerell’s diverticulum  consistssurgery. In our case cardiovascular MRI and thoracic CT, in addition to three-dimensional visualization of the heart and its relationship with the thoracic structures, have allowed the identification of abnormalities of the aorta that had escaped the cardiac examinations, even invasive, previously performed.To our knowledge this is the first description of an association between left cardiomyopathy and Kommerell’s diverticulum. The etiological or pathophysiological link between the cardiovascular anomalies observed in this case appears unclear. However, the possibility that hemodynamic changes induced by vascular malformation might have favored the development of areas of myocardial tissue damage or predisposed to the the occurrence of myocarditis should not be excluded.The search for a structural heart disease is the primary task in the assessment of ventricular arrhythmia in athletes. However, the failure to detect a significant organic substrate in the initial stage of screening does not preclude the identification of structural pathologies in the follow-up by using advanced imaging techniques. In this way we were able to identify a unique combination of rare cardiovascular disease. Future observations and further investigations are required to elucidate their pathophysiologic link.


Fifty patients referred for clinical CMR were imaged using the FB + NAV sequence. All sequences used a T2 prepared (T2prep) steady-state free precession acquisition. In-plane myocardial motion was corrected using an adaptive registration of varying contrast-weighted images for improved tissue characterization (ARCTIC). DICE similarity coefficient (DSC) and myocardial boundary errors (MBE) were measured to quantify the motion estimation accuracy in healthy subjects. T2 mapping reproducibility and spatial variability were evaluated in healthy subjects using 5 repetitions of the FB + NAV sequence with either 4 or 20 T2prep echo times (TE). Subjective T2 map quality was assessed in patients by an experienced reader using a 4-point scale .Twelve healthy adult subjects were imaged using breath-hold (BH), free breathing (FB), and free breathing with respiratory navigator gating (FB + NAV) myocardial Tp = 0.007), FB data , and FB + NAV data , and reduced MBE in BH data , FB data , and FB + NAV data . Improved reproducibility , reduced spatial variability  and improved subjective score of T2 map quality  were obtained using ARCTIC.ARCTIC led to increased DSC in BH data (0.85 ± 0.08 vs. 0.90 ± 0.02, 2-weighted images and improves the reproducibility and spatial variability of in-vivo T2 mapping.The ARCTIC technique substantially reduces spatial mis-alignment among T In carduisition . Elevatecarditis , Tako-Tscarditis , and acucarditis –7. Howevcarditis , 10.2 mapping [2-weighted images. In this technique, several T2-weighted images are acquired, each with a different T2 contrast. The signal intensity obtained from the T2-weighted images is then fit to a physical model of T2 signal decay on a per-pixel basis, leading to the creation of a T2 map. The acquisition of each T2-weighted image was initially performed using either spin echo/fast spin echo acquisitions [2-prepared (T2prep) [Quantitative myocardial T mapping , 12 is aisitions –14 with (T2prep)  steady-s(T2prep) . These s(T2prep) , 17 or u(T2prep) , 18, 19.2-weighted images is one of the main challenges in T2 mapping and is expected to have important impact on the technique precision and reproducibility.Despite the promise of this technique, its in-vivo reproducibility and precision have not been fully characterized. These two factors play a major role for clinical acceptance of any quantitative myocardial tissue characterization technique , 21. The1 mapping studies using breath-held acquisitions of ~11-17 heart beats [2-weighted images  since a rest time of ~4-6 heart beats is required between each acquisition to allow for full longitudinal magnetization recovery. Therefore, the use of a free breathing acquisition is attractive as it enables the acquisition of a larger number of T2-weighted images which may be beneficial to improve precision and reproducibility. On the other hand, free breathing acquisitions require the use of respiratory navigators to account for through plane motion and image registration algorithms to correct for residual in-plane motion [Breath-hold acquisitions can be used to reduce the impact of respiratory motion. However, some motion can still be detected in 40-60 % of patients due to their limited breath-holding capabilities, as reported by several Trt beats –25. The e motion .1 mapping [2 mapping and its impact on in-vivo reproducibility and spatial variability of myocardial T2 estimates.We recently developed a technique for Adaptive Registration of varying Contrast-weighted images for improved TIssue Characterization (ARCTIC) which we have evaluated for myocardial T mapping . In thisAll subjects were scanned using a 1.5 T Philips Achieva  scanner with a 32-channel cardiac phased array receiver coil. This study was health insurance portability and accountability act (HIPAA) compliant and the imaging protocol was approved by our institutional review board ) at the Beth Israel Deaconess Medical Center. Written informed consent was obtained from each participant.2 mapping was performed using our recently reported T2 mapping sequence [2-weighted images are acquired using an electrocardiogram (ECG)-triggered T2prep steady-state free precession (SSFP) acquisition with different T2prep echo times (TET2P). A rest cycle of 6 s was used between the acquisitions of two successive T2-weighted images to ensure full re-growth of the longitudinal magnetization. The TET2P = 0 image was acquired using 90° pulse followed immediately by a -90° pulse and a crusher gradient to ensure consistency with all other images in term of longitudinal signal reduction induced by imperfect 90° and -90° flip angles used in the T2prep. Finally, to model the signal re-growth induced by the SSFP imaging pulses, an infinitely long T2prep echo time (TET2P = ∞) was simulated by acquiring an image immediately after a saturation pulse. In this study, this sequence has been evaluated with 4 T2prep echo times  and 20 T2prep echo times . For free breathing acquisitions, a respiratory navigator positioned immediately prior to the T2prep was used for end expiratory gating (window size = 5 mm). No T2prep or imaging pulses were applied if the navigator signal was outside the gating window to enable the acquisition of undisturbed signal in the next heartbeat.Tsequence  in which2-weighted images [T2P = 0). The motion was then estimated in a two-step process. Affine motion descriptors are first estimated over a region of interest surrounding the heart. This global transformation is then provided as input of a more sophisticated local non-rigid motion estimation step using an extended formulation of the optical flow problem which enables the simultaneous estimation of both motion field and intensity variations on a per-pixel basis [The ARCTIC approach was used to compensate for in-plane motion between Td images . In thisel basis . An addiel basis –30. In tel basis . For eacel basis –34, a GPel basis .2 maps were reconstructed offline using a 3-parameter curve fitting model.Tn is the T2prep echo time of nth T2-weighted image, and A, B, and T2 are the model parameters. A, B, and T2 are estimated independently for each pixel using a Levenberg-Marquard optimizer with the online library provided in [where tvided in .2 mapping sequences in the following order:2P4TEBreath-held T2P4TE without respiratory navigatorFree breathing T2P4TE with respiratory navigatorFree breathing T2P20TE with respiratory navigator (5 repetitions).Free breathing TTwelve healthy adult subjects  without any history of cardiovascular disease underwent CMR examination. Each subject was imaged using eight T2, in-plane resolution = 2.5 × 2.5 mm2, slice thickness = 8 mm, TR/TE = 2.7 ms/1.35 ms, flip angle = 85°, 10 linear ramp-up pulses, SENSE rate = 2, acquisition window = 138 ms, number of phase encoding lines = 51, linear k-space ordering. All T2 scans were acquired in the same short axis orientation at the mid-diastolic cardiac phase using one single mid-ventricular slice.All sequences were acquired in the short axis view using a single-shot ECG-triggered acquisition with SSFP imaging readout and the following parameters: field of view = 240 × 240 mm2-weighted images without (uncorrected) and with in-plane motion correction using ARCTIC (motion corrected). Endocardial and epicardial contours were manually drawn in all T2-weighted images of all T2 mapping scans. The two contours were used to create a binary representation of the myocardium for each T2-weighted image. The DICE similarity coefficient (DSC) [ref) and the myocardial binary mask of each kth T2-weighted image (Mk) as follows:Accuracy of motion correction was evaluated in the first three scans (T2p4TE) by quantifying the motion between the Tnt (DSC)  was then2-weighted image (boundary of Mk) and the myocardial boundary of the reference image (boundary of Mref) as follows:The myocardial boundary error (MBE), which provides a local alignment measure is also reported. MBE was measured as the average distance between the myocardial boundary of each Tth point along the boundary of Mk, Mref. Since TET2P = ∞ images are very low signal-to-noise ratio (SNR) images, which makes the detection of the myocardial borders very difficult, no DSC/MBE were measured in those images. The statistical significant difference between DSCs (and MBEs) obtained with and without motion correction was evaluated using Wilcoxon signed rank tests. Statistical significance was considered at p < 0.05.Where 2 mapping was evaluated using the five T2P20TE scans. For each scan, T2 maps were reconstructed without (uncorrected) and with prior in-plane motion correction using ARCTIC (motion corrected). The endocardial and epicardial border of the myocardium and the insertion point were manually drawn on each T2 map. A six myocardial segment model [2 estimates was then performed. Spatial variability was defined as the standard deviation of T2 estimates over a given segment. Reproducibility was defined as the standard deviation over the 5 scans of the spatial average T2 values in one given segment. Both reproducibility and spatial variability are reported in average over all segments for each subject, and in average over all subjects for each segment. To investigate the motion influence in T2 mapping sequences using a limited number of T2prep echo times, this overall analysis was repeated using a subset of the T2-weighted images from each scan . The statistical significant difference between uncorrected and ARCTIC motion corrected T2 reproducibility  measured for each subject  was evaluated using Wilcoxon signed rank tests.The impact of in-plane motion correction on the reproducibility and spatial variability of Tnt model  was auto2P4TE T2 mapping sequence with respiratory navigator. All sequences were acquired in the short axis view using a single-shot ECG-triggered acquisition with SSFP imaging readout and the following parameters: field of view = 360 × 360 mm2, in-plane resolution = 2 × 2 mm2, slice thickness = 8 mm, slice number = 3, TR/TE = 2.9 ms/1.45 ms, flip angle = 85°, 10 linear ramp-up pulses, SENSE rate = 2, acquisition window = 270 ms, number of phase encoding lines = 93, linear k-space ordering. T2 maps were reconstructed without and with ARCTIC motion correction.Fifty patients referred for clinical CMR  were imaged using the free breathing T2-weighted images. Subjective assessment of uncorrected and motion correction T2 maps (150 T2 maps) followed. Each pair of uncorrected and motion correction T2 maps were shown simultaneously to the reader side by side in a random order. The reader was blinded to the reconstruction approach (uncorrected vs. motion corrected). Each map was assessed in term of overall quality . Furthermore, for each pair of T2 maps, the reader was asked to evaluate if any of the two T2 map had “1-inferior”, “2-similar”, or “3-superior” quality. Wilcoxon signed rank test was used to test the null hypothesis that the difference of overall T2 map quality scores between uncorrected and motion corrected T2 maps was zero. Statistical significance was considered at p < 0.05.A subjective qualitative analysis was performed by an experienced cardiologist. The initial motion level in uncorrected data was assessed for each slice as “no motion”, “small motion”, or “large motion” by visual inspection of all uncorrected T2P4TE sequence and to 99 heart beats for the T2P20TE sequence. The employed ARCTIC motion correction and reconstruction of one T2 map with 20 T2prep echo times was 20s.All scans were successful. The nominal scan time (assuming 100% gating efficiency) corresponded to 13 heart beats for the T2-weighted images acquired in one healthy subject using the T2P4TE sequence under breath-hold, free breathing, and free breathing with respiratory navigator gating. Motion artifacts can be observed in the reconstructed T2 maps (see white arrows). In-plane motion correction improves the spatial alignment of T2-weighted images and results in visually improved T2 map quality , free breathing data , and free breathing data with respiratory navigator gating . The MBE decreased in breath-hold data , free breathing data , and free breathing data with respiratory navigator gating .Figure 2 maps obtained in one healthy subject using the T2P20TE sequence acquired under free breathing conditions with respiratory navigator gating. T2 maps are shown when reconstructed from only 4 T2prep echo times and from all 20 T2prep echo times. The level of artifacts in uncorrected T2 maps appears higher than in motion corrected T2 maps (see white arrows). As expected, motion artifact patterns have high spatial variability in uncorrected T2 maps. Furthermore, the spatial variability of the myocardial T2 estimates appears well reduced when using all 20 T2prep echo times compared to only 4 T2prep echo times.Figure 2 measurements obtained in healthy subjects using the T2P20TE sequence. Results are shown for uncorrected and motion corrected T2 maps reconstructed using either 4 T2prep echo times or 20 T2prep echo times. Reproducibility and spatial variability are reported as uncorrected T2 maps vs. motion corrected T2 maps using ARCTIC. Improved reproducibility was observed over all subjects and myocardial segments in T2 maps reconstructed from 4 T2prep echo times  and 20 T2prep echo times . Similarly, reduced spatial variability was observed over all subjects and myocardial segments in T2 maps reconstructed from 4 T2prep echo times  and 20 T2prep echo times .Figures 2 maps reconstructed using 20 T2prep echo times had better reproducibility than those reconstructed using only 4 T2prep echo times in both uncorrected data  and motion corrected . The spatial variability of myocardial T2 estimates reconstructed using 20 T2prep echo times was also lower than the one obtained with 4 T2prep echo times in both uncorrected data  and motion corrected data .As expected, T2 maps obtained in four patients. Large regional variations and artifacts can be observed in uncorrected T2 maps (see white arrows). The proposed ARCTIC motion correction substantially improved the T2 map quality in all 4 patients.Figure 2 map quality obtained in 50 patients. Overall (N = 150 T2 maps), ARCTIC motion corrected T2 maps had higher quality score than uncorrected T2 maps . In the relative comparison of T2 map quality, uncorrected T2 maps has superior, similar, and inferior quality than ARCTIC motion corrected T2 maps in 4 maps (3 %), 99 maps (66 %), and 47 maps (31 %), respectively. Furthermore, the motion level was assessed as “no motion” in 35 slices (23%), “small motion” in 69 slices (46%), and “large motion” in 46 slices (30%). In “no motion” data, all ARCTIC motion corrected and uncorrected T2 maps received a subjective quality score of 4.0 and 97 % of them had similar relative quality. In “small motion” data, ARCTIC motion corrected T2 maps had higher subjective quality score  and superior (23%), similar (75%) and inferior (1%) relative quality than uncorrected T2 maps. In “large motion” data, ARCTIC motion corrected T2 maps had higher subjective quality score  and superior (65%), similar (28%) and inferior (6%) relative quality than uncorrected T2 maps.Figure 2 mapping. The method provides improved alignment of the myocardium in T2-weighted images acquired with breath-hold acquisitions and free breathing acquisitions with and without respiratory navigator gating. ARCTIC motion correction improves T2 map quality which results in improved reproducibility and spatial variability of myocardial T2 estimates. Finally, the CPU/GPU implementation of ARCTIC substantially reduces the computation time of the T2 map reconstruction to 20s which is suitable for clinical applicability.In this study, we demonstrate the benefit of in-vivo in-plane ARCTIC motion correction in myocardial TT2P = ∞ images since the contrast is too low to identify the myocardium. Motion correction is expected to have slightly lower accuracy in those images due to the expected limited ability to compensate for complex motion.DSCs and MBEs found in this study are in good agreement with previous studies –25, 38. The ARCTIC approach successfully corrected the encountered motion in all subjects. In this study, the heart motion patterns were mainly influenced by the breathing activity of the subjects and to lesser extent to their RR-interval variations. However, the motion pattern can be more complex in patients imaged during arrhythmic events. The performance of the method in such conditions was not investigated and should be addressed in future work.2 mapping was improved using ARCTIC. The use of 20 T2-weighted images improved the reproducibility and the spatial variability of T2 mapping (over the use of only 4 T2-weighted images) by a factor of 2 and 1.4, respectively. Therefore, the choice of the number of T2prep echo times depends on the desired trade-off between acquisition time and T2 map quality. Further studies are warranted to determine the clinically relevant threshold providing satisfactory T2 map quality in a reasonable amount of time.The reproducibility and spatial variability of T2 estimates were found similar in all myocardial segments when using 20 TEs. However, slight differences seemed to be observed when using 4TEs only, especially in the myocardial segment #4 . Several factors could have contributed to this observation including 1) increased sensitivity to cardiac motion and partial voluming in the free wall due to reduced wall thickness, 2) increased field inhomogeneity in myocardial segments located at the heart/lung interface. Future studies are warranted to study the impact of each of these factors.Reproducibility and spatial variability of T2 mapping sequence. The ARCTIC approach is expected to provide similar motion correction performance using other T2 mapping sequences. Nevertheless, the impact of motion correction on the reproducibility and spatial variability of other T2 mapping sequences may be different and is beyond the scope of this study. Furthermore, all data were acquired in 2D. 3D myocardial T2 mapping may represent a valuable approach for true 3D assessment of pathological tissues [2 mapping.In this study, the data were acquired using our recently developed T tissues , 40. The2P20TE sequence and were thus not acquired using the T2P4TE sequence. However, since the T2P20TE sequence was acquiring with respiratory gating, the potential bias in reproducibility and spatial variability obtained in the 4TEs data should have been kept to the minimum. Finally, the study was only performed in healthy adult subjects with limited sample size. Further studies are warranted to confirm the benefit of the ARCTIC approach to improve the reproducibility and spatial variability of myocardial T2 mapping in patients.There are several limitations in this study. In the in-vivo analysis of reproducibility and spatial variability, the 4TEs data were extracted from the T2-weighted images. This method improves the reproducibility and reduces the spatial variability of in-vivo T2 mapping. Furthermore, the in-vivo reproducibility and spatial variability of T2 mapping is improved using a higher number of T2prep echo times combined with ARCTIC motion correction.The ARCTIC technique substantially reduces spatial mis-alignment among T


The purpose of this study was to observe left ventricular function during acute high-altitude exposure in a large group of healthy young males.A prospective trial was conducted in Szechwan and Tibet from June to August, 2012. By Doppler echocardiography, left ventricular function was examined in 139 healthy young Chinese men at sea level; within 24 hours after arrival in Lhasa, Tibet, at 3700 m; and on day 7 following an ascent to Yangbajing at 4400 m after 7 days of acclimatization at 3700 m. The resting oxygen saturation (SaO2), heart rate (HR) and blood pressure (BP) were also measured at the above mentioned three time points.Within 24 hours of arrival at 3700 m, the HR, ejection fraction (EF), fractional shortening (FS), stroke volume (SV), cardiac output (CO), and left ventricular (LV) Tei index were significantly increased, but the LV end-systolic dimension (ESD), end-systolic volume (ESV), SaO2, E/A ratio, and ejection time (ET) were significantly decreased compared to the baseline levels in all subjects. On day 7 at 4400 m, the SV and CO were significantly decreased; the EF and FS Tei were not decreased compared with the values at 3700 m; the HR was further elevated; and the SaO2, ESV, ESD, and ET were further reduced. Additionally, the E/A ratio was significantly increased on day 7 but was still lower than it was at low altitude.Upon acute high-altitude exposure, left ventricular systolic function was elevated with increased stroke volume, but diastolic function was decreased in healthy young males. With higher altitude exposure and prolonged acclimatization, the left ventricular systolic function was preserved with reduced stroke volume and improved diastolic function. In recent years, increasing numbers of individuals have been exposed to high-altitude environments through entertainment, physical training, work, or habitation. Atmospheric pressure falls with ascending altitudes, and with it, there are decreases in the partial pressure of inspired oxygen, arterial pressure of oxygen and arterial oxygen saturation. Therefore, exposure to hypobaric hypoxia is associated with a series of adaptive responses, such as cardiovascular compensation, to combat the diminished arterial oxygen content. The initial cardiac response to hypoxia is characterized by an increase in cardiac output with tachycardia –3, whichth day of acclimatization at 4400 m.In addition, the convenience of current transportation methods allows for rapid ascent to altitudes that can compromise acclimatization and expose inexperienced climbers to the hazards of high altitude. Thus, it is urgent to identify the pattern of left ventricular function changes in high-altitude fields. We therefore assessed left ventricular function by conventional Doppler method analysis in a large group of healthy non-acclimatized young males at 500 m, within 24 h after rapid ascent by train to 3700 m and on the 72(Kg/m2) and 1.7±0.1 square meters(m2), respectively. Subjects with any one of the following conditions were excluded: respiratory diseases, cardiovascular diseases, malignant tumors, liver and kidney dysfunction and diseases of the immune system, as well as people with psychiatric disorders who could not complete the questionnaires. Thirty-two of the 139 subjects had altitude exposure history from six months ago, but no high-altitude cerebral edema or pulmonary edema had occurred. Seventy-five of them were cigarette smokers. In addition, the subjects did not take medication or receive any intervention before ascending.In total, 139 healthy young Chinese males who lived in the low lands (500 m) were recruited for the study. The average age, height, weight, body mass index (BMI) and body surface area (BSA) at the time of present study were 22.2±3.3 years old (y)(ranged from 18 to 33 years old), 171.4±4.5 centimeters, 63.4±7.1 kilograms, 21.4±2.0 kilograms/metersThe study was approved by the Ethics Committee of Xinqiao Hospital, the Second Clinic Medical College of the Third Military Medical University of the PRC. Written informed consent was obtained from all participants after being informed of the study’s purpose, procedures, and inherent risks and benefits.2 and HR), previous high-altitude exposure (>2500 m) before this travel, and symptoms related to AMS .All subjects ascended to 3700 m (Lhasa in Tibet) in 2.5 hours by plane from 500 m (Chengdu in Sichuan province). The subjects traveled by motorcar and arrived in Yangbajing  within 3 hours, where they then stayed for 7 days after they had acclimatized at 3700 m for a week . Structurd–25th, 2012 , and on the 7th day after ascending to 4400 m . Heart rate, oxygen saturation, and conventional transthoracic Doppler echocardiographic measurements were performed at the above-mentioned three time points. All of the questionnaires and measurements were non-invasive.All of the above mentioned procedures were performed at 500 m within one week before ascension to Chengdu, within 24 h after arrival at 3700 m in Lhasa at approximately 13:00 pm June 23Acute mountain sickness (AMS) is commonly experienced by people traveling to high altitudes, typically those above 2500 m. The AMS diagnoses were based on the Lake Louise score (LLS), an international standard scoring system for AMS . This de2) was measured with a pocket pulse oximeter . The blood pressure (BP) and heart rate (HR) were determined with a sphygmomanometer . These data were measured in triplicate after the subjects had rested in a seated position for 20 minutes. The mean arterial pressure (MAP) was calculated according to the systolic blood pressure (SBP) and diastolic blood pressure (DBP): MAP = DBP+ (SBP—DBP)/3.The oxygen saturation  with a probe of 2 to 4 MHz was used to measure the left ventricular end-diastolic dimension (LVEDD), end-systolic dimension (LVESD) and HR, where the left parasternal long-axis and the short-axis views at the mid-left ventricular level were obtained when the heart rate was in a steady state. The left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) were obtained by Teichholz’s formula . The strIn the Doppler examinations, the mitral inflow velocity pattern was recorded from the apical long-axis view, and the pulsed wave Doppler sample volume was positioned at the tip of the mitral leaflet during LV diastole to measure the early (E) and late (A) diastolic wave peak velocities; the E/A ratio was obtained through dividing the E wave peak velocity by the A wave peak velocity. The LV outflow velocity pattern was recorded from the apical long-axis view, with the pulsed wave Doppler sample volume positioned just below the aortic valve. Then, the time intervals for calculating the LV Tei index were measured from the mitral inflow and the LV outflow recordings  Fig. 2)Fig. 2). The continuous data are expressed as the mean ± SD. The baseline and the two high-altitude measurements in the lowlanders were analyzed using a one-way analysis of variance for repeated measures, followed by Newman-Keuls post hoc comparisons where appropriate. All data and calculations were performed with SPSS 19.0 software . A two-sided ±-level of significance of 0.05 was used for all tests, and a probability value less than 0.05 was considered to be statistically significant. Before analysis, all data were reviewed by the principal investigator for completeness.Within 24 hours after arrival at 3700 m, 75 of 139 subjects (53.96%) met the criteria for AMS; there were 43 mild AMS cases and 32 severe AMS cases. There were still 27 subjects (19.42%) who conformed to the Lake Louise score criteria after 7 days of acclimatization at an altitude of 4400 m, ten of whom had severe AMS, comparatively, and seventeen of whom had mild AMS. Fortunately, there was no one experienced high-altitude cerebral edema or pulmonary edema during this trip.2 value was significantly reduced in all subjects from 98.42±x0.94% to 88.92±2.67% (P < 0.001) at resting state upon acute high-altitude exposure. However, the HR was significantly elevated from 62.47±8.98 beats/min to 82.91±11.56 beats/min (P < 0.001) under hypoxic conditions. However, the BP showed almost no change. After 7 days acclimatization at an altitude of 4400 m, the SaO2 value was further reduced from 88.92±2.67% to 87.96±2.57% (P < 0.01). However, the HR was further elevated from 82.91±11.56 beats/min to 86.85±15.55 beats/min (P < 0.01). The BP was increased after 7 days acclimatization at an altitude of 4400 m compared with the BP within 24 hours upon arrival at 3700 m, and the diastolic blood pressure (DBP) and mean arterial pressure (MAP) were significantly higher than those at sea level.As shown in Comparisons were made between measurements at three different altitudes with respect to global left ventricular size . Within Regarding the global LV systolic function, as expected, the EF, FS, CO, and CI increased significantly under hypoxic stress compared to the corresponding baseline values in all subjects . HoweverAfter 7 days of acclimatization at a higher altitude , the SV, SI, CO and CI decreased significantly compared to the corresponding measurements in Lhasa (3700 m) in all subjects (P < 0.01) , but theAs shown in Most investigations have reported that altitude-related hypoxia induces tachycardia ,17, whicIn our study, the LV contractility was elevated during exposure to high altitude in all subjects. This is in keeping with previous findings that suggested that LV systolic function was improved in hypoxic healthy volunteers –3,22,23 With acclimatization to higher altitudes, cardiac output tended to decrease with increased hemoglobin and a greater capacity for carrying oxygen to tissues. Furthermore, the stroke volume was obviously reduced because of significant decrease in LV preload in all subjects. There are two possible explanations for the decreased LV preload. The first would be LV relaxation dysfunction because of a reduced energy supply ,33. The The LV Tei index has been proven to be a sensitive indicator of the global left ventricle function . In the Several limitations exist in our study. First, in this study, all of the subjects were young adult males, which makes it difficult to extend our findings to other populations. Second, tissue Doppler imaging (TDI) was not used in this study; instead, we performed M-mode and pulse Doppler echocardiographic examinations that are commonly used in the clinic. In future studies, TDI will be used, as it will provide a more comprehensive evaluation of cardiac function. Lastly, we did not examine changes in the blood volume, plasma volume, erythrocyte volume or urine volume in this study, and thus, the reason for the preload reduction is not clear.In conclusion, left ventricular contractility is elevated, but diastolic function was decreased during exposure to high altitude, which is associated with an improvement in the LV ejection fraction, fractional shortening and stroke volume in healthy young males. With higher altitude exposure and prolonged acclimatization, the left ventricular systolic function was preserved, and there was improved diastolic function, which is associated with a preserved LV ejection fraction and fractional shortening and an elevated E/A ratio but a decreased stroke volume in all subjects.


Supplemental Digital Content is available in the text. The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown.P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death  and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E′, and left ventricular mass index .Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after adjustment for known prognostic factors. Mortality, despite treatment progress, remains high.7 Over the last decade, new chemotherapy regimens and stem cell transplantation have been associated with improved survival in patients with AL amyloidosis, but the prognosis remains poor in those with cardiac involvement, which also contributes substantially to treatment-related morbidity and mortality. There remains a large unmet need for improved noninvasive criteria to stratify risk in selecting optimal therapy while avoiding serious toxicities.The prognosis of immunoglobulin light-chain (AL or primary systemic) and transthyretin (ATTR) amyloidosis is substantially influenced by the presence and severity of cardiac involvement, which then governs therapeutic strategies.1525Editorial see p Clinical Perspective on p 15799 Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) identifies myocardial infiltration: after the administration of contrast, CMR shows a characteristic pattern of global subendocardial LGE coupled with abnormal myocardial and blood-pool gadolinium kinetics.11 However, despite excellent diagnostic accuracy for the presence of amyloid, conflicting results have been reported for the prognostic impact on AL amyloidosis, and no studies have been published in ATTR amyloidosis.19 Newer techniques, particularly phase-sensitive inversion recovery (PSIR), an LGE image reconstruction technique that is less sensitive to operator choice of null point and renders signal intensity truly T1 weighted, may better reflect extent of cardiac involvement20 and thereby improve risk stratification.Cardiac amyloid deposition represents a key process in amyloid pathophysiology.We report here a prospective CMR study conducted in amyloidosis in which we investigated the prognostic value of LGE in 250 consecutive CMR-eligible subjects. The aims of the study were to assess the LGE patterns and the benefit of new more robust approaches (PSIR), the correlation with the cardiac amyloid burden, and the prognostic impact of LGE in both AL and ATTR cardiac amyloidosis.TTR gene. The third group was made up of 9 subjects with amyloidogenic TTR gene mutations  defined as individuals with no evidence of clinical disease .Subjects were prospectively recruited at the National Amyloidosis Center, Royal Free Hospital, London, UK, from 2010 to 2014 . Outcome  was ascertained from death certificates. A total of 250 patients were categorized into 3 groups. The first group included 119 subjects with biopsy-proven systemic AL amyloid , with biopsies from the myocardium  or other tissues . The second group comprised 122 consecutive, consenting patients with ATTR amyloidosis . Sixty-nine percent (n=84) had histological proof of ATTR amyloidosis by Congo red and immunohistochemical staining of myocardial  or other  tissues. The presence of cardiac amyloid was defined by the presence of ATTR amyloid in a myocardial biopsy or positive technetium-labeled bone scintigraphy using 3,3-diphosphono-1,2-propanodicarboxylicacid (DPD scintigraphy). All subjects underwent sequencing of exons 2, 3, and 4 of the We excluded all patients with contraindications to CMR: glomerular filtration rate <30 mL/min and CMR-incompatible devices. All ethics were approved by the University College London/University College London Hospital Joint Committees on the Ethics of Human Research Committee, and all participants provided written informed consent.All subjects underwent standard CMR on a 1.5-T clinical scanner . Within a standard clinical scan , LGE imaging was acquired with magnitude-only inversion recovery (MAG-IR) and PSIR sequence reconstructions in 43% of patients.21 with regions of interest drawn in the 4-chamber view at the level of the basal and mid inferoseptum .22 After a bolus of gadoterate meglumine  and standard LGE imaging , the patient was removed from the scanner. The extracellular volume (ECV) measurement approach used equilibrium CMR with a primed infusion: At 15 minutes after bolus, an infusion at a rate of 0.0011 mmol·kg−1·min−1 contrast  was given. Between 45 and 80 minutes after bolus, the patient was returned to the scanner with the infusion continuing, and the T1 measurement was repeated using the same parameters of the precontrast ShMOLLI sequence.T1 measurement was performed with the use of the shortened modified look-locker inversion recovery sequence (ShMOLLI)During interpretation, before our adoption of PSIR for all amyloidosis patients, because myocardial nulling can be difficult in the presence of amyloid, any confusion with MAG-IR images was resolved by selecting the images that most matched the postcontrast T1 maps, with “bright” LGE expected to correlate with areas with the lowest postcontrast T1 .The LGE pattern was classified by 2 different observers (M.F. and S.P.) into 3 groups according to the degree of transmurality: group 1, no LGE; group 2, subendocardial LGE ; and group 3, transmural LGE  was analyzed for concordance or discordance with the postcontrast T1 maps that were used as the truth standard Figure . We conshttp://www.r-project.org/). All continuous variables were normally distributed (Shapiro-Wilk) except for NT-proBNP and troponin T, which were therefore ln-transformed for bivariate testing. These are presented as mean±SD, and nontransformed NT-proBNP is presented as median and quartiles 1 through 3. Comparisons between groups were performed by 2-way ANOVA with post hoc Bonferroni correction. The χ2 test or Fisher exact test was used to compare discrete data as appropriate. Correlations between parameters were assessed with the Pearson r or Spearman ρ. To assess the agreement of the assignment of the LGE pattern by 2 different observers, the intraclass correlation coefficient was calculated. Statistical significance was defined as P<0.05.Statistical analysis was performed with IBM SPSS Statistics version 19  and the R programming language , meaning that operator TI selection was mainly incorrect. Ten patients with MAG-IR only had no LGE images that matched the T1 mapping for classification . All patients with PSIR LGE had diagnostic images. PSIR LGE and T1 maps were never (0%) discordant Figures  and 3. MP<0.05) and transmural LGE more prevalent in ATTR . Apparent transitions are evident, with subendocardial LGE appearing at an ECV of 0.40 to 0.43 for AL and 0.39 to 0.40 for ATTR and transmural at an ECV of 0.48 to 0.55 for AL and 0.47 to 0.59 for ATTR. However, 39% of the patients with no LGE had ECV elevation compared with normal range (ECV elevation between 0.32 and 0.40). Of the patients with no LGE and increased ECV, 4 patients had mutant ATTR (and DPD was grade 1 in 3 patients and grade 0 in 1 patient), and 17 patients had AL amyloidosis.Increasing LGE  was associated with increasing ECV  was associated in both AL and ATTR with lower systolic blood pressure, ECG changes , increased NT-proBNP, structural and functional changes , increasingly abnormal tissue characterization , 67 of 250 patients (27%) had died. Transmural LGE was a significant predictor of mortality in the overall population  in multivariable Cox models that included NT-proBNP, ejection fraction, stroke volume indexed, E/E′, and left ventricular mass indexed . NT-ProBNP and stroke volume indexed also remained independently predictive  compared with 81% for patients with subendocardial LGE  and 61% with transmural LGE . The median survival in patients with transmural LGE was 17 months in AL and 38 months in ATTR. Transmural LGE was significantly associated with mortality  was 0.67.19 Recently, considerable interest has emerged in using LGE to improve the risk stratification model,19 but studies in AL cardiac amyloidosis have been few, mostly small, and retrospective; have used nonstandardized LGE approaches; and have produced inconsistent results.19 No studies have been published in ATTR amyloidosis.Cardiac infiltration is the chief driver of prognosis in systemic amyloidosis, and stratification of patients is essential for prognosis and optimal management, including selection of patients to receive aggressive higher-risk therapies and to minimize cardiac toxicities. Echocardiography, once the gold standard cardiac investigation in amyloidosis, has limited sensitivity and specificity, and risk stratification currently places great emphasis on blood biomarkers. However, these strategies do not identify all amyloidosis patients at risk, and the findings of studies evaluating cardiac involvement by CMR have been conflicting.23 Accordingly, we believe that PSIR should be universally adopted for amyloid LGE imaging, particularly because PSIR-LGE is easily available from all scanner manufacturers (whereas T1 mapping is not yet).In the present study, the largest CMR study in amyloidosis to date, we showed that misleading results using the MAG-IR LGE technique were likely to account for the conflicting finding that have previously been published. By convention, areas with the most contrast should be displayed as bright on LGE imaging . For amyloidosis, myocardium can contain more gadolinium than blood. Under those circumstances, myocardium should appear globally bright . It is a property of MAG imaging that the signal is highly dependent and nonlinear with a user-defined choice of the TI . Indeed, in ATTR, the majority of the deaths are in patients with transmural LGE .With PSIR, 3 patterns were relatively easy to determine, and the frequently described LGE pattern of patchy LGE was not evident with PSIR . A key insight is that amyloid cardiac involvement is not dichotomous but a continuum from no LGE to subendocardial to transmural tracking increasing ECV Figure .24,25 Tr26 T1 mapping techniques provide new insights into this, being able to follow the disease at 3 different levels, that is, infiltration , edema (native T1), and myocyte response (intracellular volume), and providing new prognostic markers.27 These new biomarkers may aid diagnosis and risk stratifications and act as surrogate end points in clinical trials. However, the current limited availability and the technical challenges related to sequence- and vendor-specific differences limit the role of T1 mapping in routine clinical practice. The common use of the LGE technique in all clinical CMR scans and the availability of PSIR reconstruction on all different vendor platforms make LGE a robust and reliable approach for routine risk stratification of patients with cardiac amyloidosis.Within this spectrum, the degree of involvement is important, with transmural LGE defining the high-risk group. The prevalence of patients in the different stages of disease progression Figure  is diffeLimitations of the study are that patients were at different treatment stages, with treatment reflecting current UK practice. Cardiac biopsy was present in only a minority of patients, but this cohort of patients was fully characterized with all other clinical investigative techniques currently available, including DPD scanning. This composite diagnostic pathway is known to provide high diagnostic accuracy. The causes of death are not known because patients die locally and the National Amyloidosis center receives only notification of death, not the cause of death. Although this study highlights the prognostic role of transmural LGE for risk stratification of patients with cardiac amyloidosis, further studies are needed to assess the direct correlation between patterns of LGE and treatment-related mortality.Dr Fontana is supported by a Clinical Research Training Fellowships from the British Heart Foundation (FS/12/56/29723). A. Abdel-Gadir is supported by the Rosetrees Trust. T.A. Treibel is supported by the National Institute for Health Research (DRF-2013-06-102). Dr Moon is supported by the Higher Education Funding Council for England. Dr Bucciarelli-Ducci is supported by the Bristol NIHR Biomedical Research Unit. This work was undertaken at the University College London Hospital and University College London, which received a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme.None.