The release of myocardial necrosis biomarkers after off-pump coronary artery bypass grafting (OPCAB) frequently occurs. However, the correlation between biomarker release and the diagnosis of procedure-related myocardial infarction (MI) (type 5) has been controversial. This study aimed to evaluate the amount and pattern of cardiac biomarker release after elective OPCAB in patients without evidence of a new MI on cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE).Patients with normal baseline cardiac biomarkers referred for elective OPCAB were prospectively included. CMR with LGE was performed in all patients before and after interventions. Measurements of troponin I (cTnI) and creatine kinase MB fraction (CK-MB) were systematically performed before and after the procedure. Patients with new LGE on the postprocedure CMR were excluded.All of the 53 patients without CMR evidence of a procedure-related MI after OPCAB exhibited a cTnI elevation peak above the 99th percentile. In 48 (91%), the peak value was >10 times this threshold. However, 41 (77%) had a CK-MB peak above the limit of the 99th percentile, and this peak was >10 times the 99th percentile in only 7 patients (13%). The median peak release of cTnI was 0.290 (0.8–3.7) ng/mL, which is 50-fold higher than the 99th percentile.In contrast with CK-MB, considerable cTnI release often occurs after an elective OPCAB procedure, despite the absence of new LGE on CMR. The pathogenic process underlying this phenomenon is complex and is still not well understood. It has been the subject of many studies and has been defined in various ways. Many factors may be responsible for this elevation, and even the manipulation of the heart that is required during mechanical revascularization procedures may predispose to myocardial injury. Several definitions have been suggested for the diagnosis of myocardial infarction (MI) after coronary artery bypass grafting (CABG), and in recent years the definitions have been updated due to limitations found in the previous reports. The elevation of cardiac biomarkers is considered the main event for the diagnosis, although elevated biomarkers are not conclusive evidence of cardiac injury. The current universal definition suggested by the European Society of Cardiology (ESC)/American College of Cardiology Foundation (ACCF)/American Heart Association (AHA)/World Health Foundation (WHF) states that a 10-fold increase from baseline in biomarkers is recommended along with ancillary criteria, such as new pathological Q-waves, or new left bundle-branch block (LBBB) and/or imaging, or angiographic evidence of new occlusion of native vessels or grafts, new regional wall motion abnormality, or loss of viable myocardium. because the threshold for a worsening prognosis related to an asymptomatic increase in cardiac biomarker values is still not well defined. Uncertainty remains about which is the preferred cardiac biomarker, especially with the recently developed high-sensitivity troponin assays that could be too sensitive in this scenario. Furthermore, the avoidance of cardiopulmonary bypass in off-pump CABG may lead to lower levels of biomarker release compared with on-pump procedures.Nevertheless, the diagnosis of MI in this specific clinical setting is based on arbitrary definitions,Thus, this study aimed to quantify the release of troponin I (cTnI) and creatine kinase MB fraction (CK-MB) after CABG performed without cardiopulmonary bypass (off-pump coronary artery bypass grafting [OPCAB]) in the absence of myocardial necrosis identified by cardiac magnetic resonance (CMR) imaging with new late gadolinium enhancement (LGE) and compared them with the established values of the current universal definition of MI.22.1 This is a subanalysis of a trial published previously. Patients with angiographically documented multivessel coronary stenosis >70% by visual assessment, stable angina, preserved ventricular function, and normal baseline cardiac biomarkers were enrolled in the current study. Furthermore, they were eligible if an off-pump procedure was deemed technically feasible. All patients underwent CMR before and after the surgical procedure.Details of the Medicine, Angioplasty, or Surgery Study V (MASS-V) study design, protocol, patient selection, and inclusion criteria have been previously reported.Exclusion criteria were as follows: presence of new late enhancement on CMR after the procedure, recent MI (≤6 months); signs of manifested or suspected infections or rheumatologic disease activity; chronic renal failure (creatinine level > 2.0 mg/dL); recent (≤6 months) pulmonary embolism or venous thromboembolism; patients who did not sign the consent form; and any contraindication to CMR examination, such as the presence of a pacemaker or severe claustrophobia.2.2Blood samples were collected from each patient for measurement of cTnI and CK-MB mass before OPCAB and 6, 12, 24, 36, 48, and 72 h after the procedure. All the samples were centrifuged at 3000 rpm for 20 min and analyzed within 2 h after specimen collection. cTnI and CK-MB analyses were performed in an immunoassay analyzer . According to the manufacturer, the lower limit of detection of cTnI using a high-sensitivity kit, the ultra kit, was 0.006 ng/mL, and the 99th percentile and MI reference limits were, respectively, 0.04 and 0.76 ng/mL. The assay precision represented by the percentage coefficient of variation (% CV) was ≤10% at 0.03 ng/mL.The detection limit of the CK-MB mass kit  was 0.18 ng/mL, and the cutoff values at the 99th percentile, established by our laboratory, were 3.8 ng/mL for women and 4.4 ng/mL for men. The CVs for CK-MB mass, as specified by the manufacturer, were 3.91% at 3.55 ng/mL for women and 3.61% at 80.16 ng/mL for men.2.3 Briefly, the distal ends of the 2 suction arms of the stabilizer are placed on the beating heart on both sides of the target coronary artery. The proximal parts are fixed to the operating table. Through the application of negative pressure, the target area of the heart is sufficiently immobilized to allow the safe construction of the anastomosis of the graft with the recipient artery.Trial operators were required to perform optimum coronary revascularization in accordance with current best practices. The same team of cardiac surgeons with experience in OPCAB surgery performed the procedures in a standardized fashion. Surgical access to the heart was through a standard median sternotomy in all cases. All incisions and closure techniques were performed in the same way in all patients to limit variability among patients. The Octopus stabilizer described in detail elsewhere was used in OPCAB surgery.2.4The patients underwent scanning with a 1.5-T clinical MR scanner , and steady-state free-procession cine images were acquired in 2 long-axis (2 and 4 ventricles) views. A gadolinium-based contrast agent  was injected intravenously (0.1 mmol/kg of body weight), and contrast-enhanced images were acquired after a 5- to 10-min delay with the use of an inversion-recovery segmented sequence. Contrast-enhanced images were acquired in long- and short-axis planes identical to the cine images. Typical voxel size was 1.6 × 2.1 × 8 mm, with a reconstruction matrix of 528 and a reconstructed voxel size of 0.6 mm. The method for acquiring and analyzing CMR was standardized in our service and was reproduced according to conventional techniques. Delayed enhancement of CMR was performed with a phase-sensitive inversion recovery sequence  following a 5-min time delay after the administration of 0.1 mmol/kg contrast agent . Images were acquired in 2 long-axis planes and in a short-axis stack covering the entire left ventricle. The inversion time was meticulously adjusted throughout the acquisition to obtain optimal nulling of remote normal myocardium. The slice thickness at the apex was reduced to 5 mm to avoid a partial volume effect.2.5All patients provided written informed consent and were assigned to a treatment group. The Ethics Committee of the Heart Institute of the University of São Paulo Medical School, São Paulo, SP, Brazil approved the trial. All procedures were performed in accordance with the Declaration of Helsinki.2.6t test and the unpaired-sample t test were used to compare means within the study group or between subgroups. Chi-squared statistics with Fisher exact test were used for comparison of discrete variables. Continuous variables that were not distributed normally were compared with the Mann–Whitney U test. A probability value of <0.05 was considered statistically significant.Values are expressed as mean (± standard deviation) or median (interquartile range), as appropriate. The paired-sample 3Between March 2012 and March 2014, 326 prospective consecutive patients from the Department of Atherosclerosis at the Heart Institute (InCor) of the University of São Paulo Medical School were evaluated. Of these, 107 were excluded for various reasons; 71 were referred for percutaneous coronary intervention (PCI) and 75 to on-pump CABG. From the 73 patients enrolled in this study, 20 were excluded and 53 completed the study protocol. The main reasons for the exclusions are shown in Fig. The baseline characteristics were summarized in Table No patient had evidence of new “Q” wave pathology or new LBBB activity on the electrocardiogram performed after CABG.3.1The median value of the peak cTn was 2.0 ng/mL, which corresponds to a 50-fold increase from the 99th percentile. All patients had cTnI values below the 99th percentile before the procedure.Of these patients, 5 (9%) had elevation between the 99th percentile and the threshold of 10 times the 99th percentile. The 48 (91%) remaining patients had elevation above the threshold of 10 times the 99th percentile. No patient had a cTn value below the 99th percentile after surgery.Regarding the biomarker CK-MB mass, the median peak value was 14.6 ng/mL for females and 12.7 ng/mL for males. All patients had CK-MB values below the 99th percentile before the procedure.Additionally, we noted that 40 (76%) patients had an elevation between the 99th percentile and the threshold of 10 times the 99th percentile, 7 (13%) had peak values higher than 10 times the 99th percentile, and 6 (11%) had no elevation in this biomarker Fig. .The pattern of cTn elevation in each moment of evaluation after surgery is described in the chart shown in Fig. P < 0.01 in all groups.The comparisons of the levels of cTn in the different periods after the procedure showed a statistically significant difference, The pattern of CK-MB elevation in each moment of evaluation after surgery for males and females is described in the chart shown in, respectively, Figs. P < 0.01 in both groups.The comparisons of CK-MB values in the different periods after the procedure showed statistically significant differences, 4In this study, based on the cutoffs recommended by the current guidelines, we found marked differences in the results, depending on which biomarker was analyzed. The elevation of cTnI was above the 99th percentile in all patients after surgery, with the majority exceeding 10 times the 99th percentile value reaching up to 50 times the cutoff. On the other hand, the release of CK-MB was predominantly below the 10-fold 99th percentile threshold. Thus, cTn falsely indicated MI in the majority of patients, while CK-MB elevation was consistent with myocardial injury related to the cardiac procedure. Of note, both patterns occurred regardless of the absence of new LGE in CMR performed after OPCAB. Moreover, all patients experienced good recovery after cardiac revascularization.,6Numerous reasons can lead to periprocedural myocardial injury with release of cardiac biomarkers after CABG. These include direct myocardial trauma from suture placement or manipulation of the heart, inadequate intraoperative cardiac protection, microvascular events related to reperfusion, myocardial injury induced by oxygen free radical generation, or failure to reperfuse areas of the myocardium that are not subtended by graft table vessels. It should be noted that biomarker elevations after CABG could be secondary to a variety of factors, including underlying pathology, surgical technique, and perioperative complications, and may not be indicative of a vascular event. Klatte et al reported that CK-MB was an independent predictor of 6-month mortality . Moreover, the analysis of the consecutive area under the receiver operating characteristics curve suggested that the optimal cutoff point ranged from 5 to 10 times the ULN. Higher cutoff values (>10 times the ULN) were associated with higher specificity and negative predictive values, yet suffered from lower sensitivity. Domanski et al in a meta-analysis demonstrated increased cardiovascular mortality within 30 days in patients with CK-MB elevation >5 times the 99th percentile and with an elevation of cTn above 40 times the 99th percentile. Hence, these studies assessed CK-MB levels and associated its elevations with cardiac events. The extrapolation from these results of cTn thresholds and diagnosis of periprocedural MI should be made carefully. The main drawback of these trials is that the group of individuals who reach the 5 times threshold of cardiac biomarkers is essentially different. There were those who had an isolated rise in biomarkers among those with real myocardial necrosis and consequently impaired prognosis. Therefore, the prognosis may be driven by the extent of necrosis, regardless of the cause of injury.The current ESC/ACCF/AHA/WHF statement advocates the use of cTn assay for detection and quantification of type 5 MI. Nevertheless, the current threshold was primarily based on studies that reported a significant correlation of CK-MB with adverse events, such as death, shock, and prolonged length of stay in the intensive care unit. The criterion based on the threshold of 10-fold upper reference limit for cTn alone is clearly too sensitive, but higher thresholds appear to be more accurate. Pegg et al assessed the utility of biomarkers cTnI and CK-MB after CABG associated with results of CMR imaging. cTn elevation was observed above the value of 10 times the 99th percentile in all patients. The median value of cTnI peaks was 4.7 ng/mL in patients without further delayed enhancement in CMR after the procedure, which corresponds to twice the value found in our study. However, the median value of CK-MB peak was 12.4 ng/mL, a similar value to that found in our study. Of note, this study applied the same immunoassay  as that used in our trial. However, differently from the present study, the authors included in the analysis 2 different operative techniques and patients with impaired ventricular function. It has been shown that on-pump and off-pump procedures are associated with distinct patterns of cardiac biomarker release.Furthermore, the transition from CK-MB results to cTn results was made prior to the thorough understanding of the prognostic implications of cTn elevation after CABG. They also showed that cTnT levels were higher in this respect than measures of CK-MB. The same authors have also reported the 1-year outcome of 136 patients who underwent isolated CABG. During this time, 7 (5%) patients died. They found that median cTnT levels were higher among those patients who died, and that a cTnT level in the highest quintile at 18 to 24 h was the strongest independent predictor of mortality . Similarly, Croal et al assessed the prognostic importance of cTnI in 1365 patients undergoing cardiac surgery who were followed up at 30 days, 1 year, and 3 years after surgery. Their study confirmed that cTnI levels are frequently elevated, and patients with cTnI levels in the highest quartile are at higher risk. Again, all these studies assessed cTn levels and correlated them to cardiac events. They did not evaluate MI and thus, regarding the proposed MI definition, outcomes from these studies should be interpreted with caution.The present study confirms that cTn levels are usually elevated after off-pump CABG. Impaired outcome has been reported for cTn values that were elevated to the highest quartile of quintile of the measurements. A cTnT threshold (1.58 ng/mL) was chosen by Januzzi et al, who reported a correlation with in-hospital mortality  and death/MI (OR 60.1 [95% CI 7.34–492.1]). The same authors have demonstrated that cardiac cTnT levels in the upper quintile were significant independent predictors of in-hospital complications. In this cohort, both cTnT levels taken immediately postoperatively and those assayed between 18 to 24 h after surgery were independently predictive of a complicated in-hospital course.Unlike CK-MB, the interpretation of cTn varies depending on whether cTnT or cTnI is used and which of the variety of available cTnI methods is used. Moreover, the lack of standardizations of such assays adds complexity to the diagnosis. The thresholds for cTn are no longer comparable to the historic values, because of reductions to the lower limit of detection seen with new-generation cTn assays that have altered the ability to detect myocyte necrosis. Finally, the type of operation is a significant confounder when one interprets postoperative biomarker levels, because more complex surgeries are associated with greater elevations. This should be taken into account when values are interpreted. The greater elevations are likely associated with several features, including length of time on bypass and myocardial damage due to the surgery itself. In addition, Wu et al identified focal images of delayed enhancement by gadolinium in the CMR after acute MI, with detection areas up to 0.16 g. However, CMR studies have reported that cTnI has a low discriminatory power for detecting MI after coronary artery bypass procedures. Lim et al reported excessive sensitivity of cTnI compared to CK-MB in patients after PCI, even in the absence of new delayed enhancement in the CMR. Van Gaal et al conducted a study that compared the rise in cTn and the new onset of delayed enhancement in the CMR after surgical and percutaneous revascularization. It was observed that all patients had elevated cTn, even those with no evidence of new LGE on CMR after surgery. In addition, the average SYNTAX score value was similar to the value obtained in our study and showed no statistically significant difference between the groups with or without new delayed cardiac enhancement after the procedure. Thus, CMR studies have demonstrated that usual cTnI elevations are poor for detecting type 5 MI. Although light elevations of cTnI may be due to myonecrosis not detectable by CMR, the prognostic significance of such minor elevations has not been associated with a worse prognosis. Moreover, even using CMR that is the most sensitive imaging technique so far to evaluate myocardial fibrosis, the regular biomarker elevation did not reveal signs of MI.Among the noninvasive imaging methods recommended for detection of MI after postoperative myocardial revascularization, CMR imaging was used in our study to exclude from our analysis those patients with new detectable areas of necrosis after surgery. CMR has been used for assessment of coronary hypoperfusion extension and myocardial necrosis. Kim et al reported sensitivity to myocardial necrosis detection of up to 99% in the acute phase of MI.In conclusion, assuming that biomarkers of myocardial necrosis have limited diagnostic accuracy in myocardial injury, the challenges faced for the establishment of definitive values for the diagnosis of myocardial damage include new cutoff values for cTnI. Troponin did not indicate injury and MI by the excessive sensitivity demonstrated and by the arbitrary limit of 10-fold the 99th percentile threshold. cTn may still be valuable in this context, but its thresholds should be carefully reviewed in future studies. When the current definition of MI after OPCAB was used, CK-MB had greater accuracy and should be reviewed as a marker of choice.


Echocardiography is vital in the routine assessment and management of atrial fibrillation (AF). We performed a systematic review of the validity and reproducibility of echocardiographic left ventricular systolic and diastolic function in AF, and optimal acquisition methods.n = 444) r = 0.47 to 0.79; IVRT (n = 177) r = –0.70 to –0.95; E/Vp` (n = 55) r = 0.63 and 0.65; pulmonary vein diastolic flow (n = 67) r = –0.80 and –0.91. Elevated E/e’ (>15) was associated with functional capacity, quality of life, and impaired prognosis. For optimal acquisition in AF patients, cardiac cycles with controlled heart rate (<100 beats/min) and similar preceding and pre-preceding RR intervals are required. Cardiac cycle length and equivalence were more important than the number of beats averaged.Online databases were searched for studies in patients with AF at the time of echocardiography (1960 to August 2015), prospectively registered with PROSPERO (CRD42015025297). The systematic review included 32 studies from 3 066 search results (1 968 patients with AF). Average age was 67 years, 33% were women, mean LVEF 53% (±10%), and average E/e’ 11.7 (±2.7). Data on the validity and reproducibility of systolic indices were extremely limited. In contrast, diastolic parameters demonstrated correlation with invasive filling pressure and adequate reproducibility: E/e’ (With careful selection of appropriate cardiac cycles, echocardiography is a valid tool to identify diastolic dysfunction in AF, and E/e’ is an independent marker of clinical status and adverse prognosis. However, data on systolic function was extremely limited and requires further prospective study and assessment of variability in clinical practice. What’s new?The new 2016 ESC Guidelines on AF recommend echocardiography in all AF patients to guide management (I C).In this systematic review, data on the validity and reproducibility of systolic indices in AF patients were extremely limited; the best measure of systolic function and acquisition method in AF are priorities for future research.Diastolic parameters in AF have been validated against invasive filling pressure with adequate reproducibility. Elevated E/e’ (>15) is also associated with functional capacity, quality of life, and impaired prognosis.Measurement of systolic and diastolic function in AF is optimized when the two preceding cardiac cycles have similar RR-intervals and the heart rate is controlled (<100 beats/min).Atrial fibrillation (AF) is an increasingly common heart rhythm disturbance that leads to frequent hospital admissions, heart failure, stroke, and higher mortality.The loss of synchronized atrial contraction and altered left atrial pressure is likely to affect the reproducibility of echocardiographic measurements in AF. Factors that have been implicated include the ratio of preceding to pre-preceding cycle length and heart rate during image acquisition. Both of these influence the volume of ejection and consequently the results of the most commonly-used measurements of LV function, particularly where these are taken over a number of cardiac cycles. Joint guidelines published by the American Society of Echocardiography and the European Association of Cardiovascular Imaging suggest a minimum of five beats in AF patients, although this is based on consensus opinion.We performed a systematic and focused review of published literature on the use of echocardiography for determination of systolic and diastolic LV function in patients with AF. Our main objectives were to assess the validity of echocardiographic measures whilst in AF, both against other modalities and clinical outcomes, and the reproducibility of these parameters. A further objective was to appraise the acquisition of images. This includes the optimal number of repeated measurements and cardiac cycle lengths that would reduce variability of systolic and diastolic evaluation and allow confidence in the echocardiographic diagnosis of systolic or diastolic dysfunction in AF.http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015025297).All studies reporting validity or reproducibility data on LV systolic or diastolic function in AF patients were examined. There was no restriction on study design, however only adult populations with AF at the time of echocardiography were considered. Exclusion criteria included case reports, animal studies and studies that were only published in abstract form or in a language other than English. All editorials, commentaries and informal reviews of other literature were also excluded, as were studies only assessing left atrial size or function. An online search was performed of PubMed and the Cochrane library , including the broad terms ‘atrial fibrillation’ and ‘echocardiography’ using MESH headings and title/abstract searches, including syntax variations. We also conducted manual screening of relevant reviews and reference lists. The systematic review was reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and prospectively registered with the PROSPERO database of systematic reviews . For diastolic function, we included assessment of isovolumic relaxation time (IVRT), mitral E-wave deceleration time, the ratio of mitral peak E velocity to tissue Doppler early diastolic velocity e’ (E/e’), pulmonary venous (PV) flow diastolic deceleration time (PVd-DT), and the ratio of mitral peak E velocity to the velocity of diastolic flow propagation measured with colour Doppler M-mode (E/Vp). For all parameters, we extracted data on validity against other modalities  and estimates of intra and inter-operator reproducibility. We also noted the method by which studies collected data, including the number of repeated measures and cardiac cycle lengths. A secondary outcome was to record average values of echocardiographic measures in AF, for comparison with published norms in patients with sinus rhythm.Data on validity  and reproducibility (both intra- and inter-observer variability) were extracted by three investigators independently , and tabulated in a standardized data-extraction form. Study quality was assessed using the Risk of Bias Assessment Tool for Non-randomized Studies (RoBANS), which addresses selection bias, exposure measurement, blinding, the completeness of outcome data, and selectivity of reporting.Baseline demographics were pooled from all studies providing suitable data (including variance where applicable), and are summarized as a weighted mean according to sample size. Outcomes were synthesized qualitatively. Meta-analysis of comparative data between AF and sinus rhythm was not possible due to the limited studies available and a lack of published data on the variance of outcome measures. Analyses were performed on Stata Version 14.1 .Figure Table Table Table S1).The search strategy identified a total of 3 066 records of which 2 945 were excluded, primarily due to lack of relevance to echocardiography in AF, and a further 89 excluded after full text review , whereas LVEF and other measures of systolic function were not independently significant. The optimal, post-hoc defined GLS cut-off for predicting event-free survival was –12.5%, and this incrementally added to clinical predictors of adverse outcome.Data for the validity of systolic function indices in patients with AF were extremely limited. We found no external validation studies . There were however examples of within-study or internal validation .Table ,,,,Reproducibility of systolic function indices are summarized in Table n = 177) and inverse correlations with PCWP were all highly statistically significant, ranging from –0.70 to –0.95.,,,n = 324), of which 2 found no correlation with PCWP,,,,,n = 444) showed significant association with PCWP, ranging from 0.47 to 0.79, and including e’ derived from both septal and lateral positions.,,,,n = 55 and n = 67, respectively) and both parameters showed a high degree of correlation with PCWP.,,,Considerably more data were available for the use of diastolic parameters in AF (n = 40) as those with sinus rhythm (n = 100).,β = –0.12; P = 0.032).P = 0.002), unlike clinical and echocardiographic parameters such and age, BNP, or LVEF.In regard to clinical outcomes, a retrospective analysis of 230 AF patients identified that septal E/e’ >15 was independently associated with mortality during follow-up of 245 (± 200) days, both in patients with impaired and preserved LVEF.Table n = 997).,,,,P < 0.05),Reproducibly of diastolic indices is summarized in The irregular RR interval in AF has led to concern about the reliability of both systolic and diastolic measures, and there is clinical uncertainty about the number of repeated measures required and optimal cycle length. Historical data have shown that the RR interval affects LVEF in AF patients, more so than in sinus rhythm.r = 0.97, P < 0.001).r = 0.94, P < 0.001).,r = 0.47 and 0.44, respectively).With regard to the number of repeated measurements required, when preceding and pre-preceding RR interval lengths are equivalent (<60 ms difference), measurement of PLSS in patients with persistent or permanent AF was similar using a single index-beat, as compared to averaging 15 cardiac cycles .,,As all of the studies were undertaken on patients in AF, the pooled data gives clinical guidance as to expected average values. The weighted-mean LVEF was 52.5%, and although a number of studies either excluded or only enrolled those with heart failure, this was similar to the RealiseAF Global Registry (LVEF 54.3% in persistent and 53.3% in permanent AF).Table In all cases, there is the assumption that echocardiographic parameters are reliable in AF, despite the irregular ejection and rate. We have shown that stroke volume and LVEF do vary according to cycle length, particularly in respect to the RR intervals preceding measurement. In contrast to sinus rhythm, echocardiographers need to carefully appraise how and when to acquire measurements in order to accurately identify LV dysfunction in AF patients. Simultaneous assessment of both E and e’ are now available in order to provide a single-beat analysis of E/e’ . There are theoretical advantages to this process in reducing error, particularly in AF where successive beats are likely to vary. The dual Doppler method appears to offer better validation vs. invasive PCWP  and there was limited data above a heart rate of 100 beats/min. Finally, considering the importance of diagnosing heart failure in patients with AF, and how common these conditions are in clinical practice, the relatively small number of studies identified in this systematic review is a surprising limitation, and one that requires further attention.In selected patients with atrial fibrillation, diastolic echocardiographic parameters have been validated against invasive filling pressure, and E/e’ is an independent marker of functional impairment and adverse prognosis. Averaging single-beat assessments are reproducible and should be acquired in cycles with similar preceding length and controlled heart rate. However, data on the validity and reproducibility of systolic indices are extremely limited. Considering the importance of heart failure and assessment of systolic function in AF, further assessment of variability in routine clinical practice is urgently needed.Europace online.Conflict of interest: All authors have completed the ICMJE conflict of interest statement and report no conflicts. DK discloses non-financial support from Daiitchi Sankyo, research grants from Menarini and lecture fees from AtriCure, all outside the submitted work; and Lead for the Beta-blockers in Heart Failure Collaborative Group (BB-meta-HF) and the RAte control Therapy Evaluation in Atrial Fibrillation (RATE-AF) trial. MM, ES and RS have no disclosures to report. BAP discloses research support and honoraria from GE Healthcare and Hitachi-Aloka, all outside the submitted work.DK is supported by a National Institute of Health Research (NIHR) Career Development Fellowship (CDF-2015-08-074). The opinions expressed in this paper are those of the authors and do not represent the NIHR or the UK Department of Health.Supplementary Table S1Click here for additional data file.


Introduction: Two-dimensional (2D) strain echocardiography has emerged as a novel methodfor early diagnosis of myocardial dysfunction in patients receiving anthracycline chemotherapy.Certain myocardial segments might be more vulnerable for development of dysfunction.Methods: Sixty-three patients with breast cancer who were deemed amenable for anthracyclinechemotherapy were prospectively studied from March 2013 to March 2015 in University Hospitalsettings. Global left ventricular (LV) ejection fraction (EF), fractional shortening and the strainover 17 segments of the LV were examined using 2-dimensional transthoracic echocardiography(TTE) before and after chemotherapy. More than 15% reduction in longitudinal peak systolicstrain (LPSS) was considered significant.Results: The mean age of patients was 47 ± 10 years. LVEF was 59.7 ± 6.5% at baseline. Significantreduction of global LPSS was detected in 13% of patients. A significant LPSS reduction occurredin 32.4% of 1071 segments examined following chemotherapy. LPSS significantly decreasedin 28% of apical segments, 31% of mid segments and 37% of basal segments. LPSS reductionoccurred more frequently over the basal segments than all other segments (P = 0.031).Conclusion: Segmental pattern appears to exist in LPSS reduction following anthracycline therapy.As significant segmental decreases can be seen in the setting of unchanged global LPSS, segmentalevaluation of LPSS might be a more accurate way for assessment of myocardial function. The risk of clinical cardiotoxicity increases with increasing dosage of anthracyclines.3 Studies suggest that the incidence of HF with 400 mg/m2, 550 mg/m2, and 700 mg/m2 dosages is 3%-5%, 7%-26%, and 18%-48%, respectively.4The association between anthracyclines and cardiovascular complications has been established, and early diagnosis of these complications is pivotal in appropriate management of patients. Cardiotoxicity caused by chemotherapy constitutes a wide range from subclinical dysfunction to significant heart failure. Cardiotoxicity caused by anthracyclines is classified into acute, early onset chronic progressive and late onset chronic progressive.5 Several mechanisms for anthracycline-induced cardiotoxicity have been proposed but formation of free radicals is the most important accepted mechanism.6 Left ventricular ejection fraction (LVEF) as assessed by conventional echocardiography is the routine method of evaluating left ventricular function. However, LVEF is a measure of global myocardial function and may lack the sensitivity to detect regional myocardial dysfunction. Additionally, it is limited by several technical factors.7 As earlier detection of cardiotoxicity is of paramount importance in these patients, two-dimensional (2D) strain echocardiography has emerged as a viable method for timely detection of subtle myocardial dysfunction. Remarkably strain values are influenced by blood pressure and heart rate.8 According to expert consensus, a relative percentage reduction of longitudinal peak systolic strain (LPSS) of >15% from baseline is considered of clinical significance in patients undergoing cancer treatment.9 Additionally, considering the segmental variations in normal values of regional strain, segmental specific normal range has been introduced.8 A few studies have focused on the regional changes in strain in these patients, however the results have been inconsistent.10Previous history of chemotherapy with anthracyclines; concomitant use of other cardiotoxic drugs , female sex, history of cardiovascular disease, old age and prolonged duration of treatment with anthracyclines are among the risk factors for development of anthracycline cardiotoxicity.The objective of this research was to assess the global, regional and segmental changes of LPSS assessed through 2D strain echocardiography in adult patients with undergoing anthracycline chemotherapy for breast cancer.This is a prospective study conducted on female patients with biopsy-proven breast cancer undergoing chemotherapy with anthracyclines. Patients were recruited from the university-affiliated oncology hospital. A trained research team member obtained written informed consent from each participant. Female patients who were diagnosed with breast cancer and who were candidate for anthracycline therapy between March 2013 and March 2015 were considered for enrolment.2 and cyclophosphamide 600 mg/m2. Patient characteristics including age, vital signs, height, weight, smoking status and comorbidities including hypertension and diabetes mellitus were recorded. After four cycle of chemotherapy, with three-week intervals between the consecutive cycles, (i.e. approximately 3 months after baseline study), participants were reassessed by conventional and longitudinal 2D-strain echocardiography and the study variables were measured and compared with baseline findings.Patients with a previous history of treatment with cardiotoxic drugs, non-sinus cardiac rhythm, history of myocardial infarction or symptomatic heart failure, previous cardiac surgery, and thoracic radiotherapy. Additionally, patients were excluded if they had significant valvular stenosis/regurgitation or LVEF less than 35% in the baseline echocardiography. Left ventricular (LV) systolic function was evaluated using both 2D-strain echocardiography and conventional echocardiography at baseline for each patient during the 72 hours prior to the initiation of chemotherapy. Patients were treated with doxorubicin 60 mg/mA single experienced cardiologist performed all echocardiography examinations by a single echocardiography machine . In all patients, enrolled in the study conventional echocardiography was performed on the left lateral decubitus position and cavity sizes were measured using the M-mode based on the parasternal long axis view. Left atrial volume index (LAVI) was measured in apical-2-chamber and apical-4-chamber views and was assessed using the area length method. The results were indexed based on body surface area of the enrolled patients. The mitral valve flow was measured by placing a sample volume Doppler at the tip of the mitral valve leaflets. Tricuspid annular plane systolic excursion (TAPSE) was measured by placing a curser of M mode such that one end was on the lateral side of the tricuspid valve and the other end was on right ventricular apex. The 2D strain assessment was carried out in a 2D environment, and AFI  software was used in a multi-dimensional environment such that an apical-4-chamber view was captured in one cycle and the apical-4-chamber, apical-2-chamber, and apical-3-chamber views were also obtained simultaneously. The views were stored in the software and the 2D strain assessment was conducted using AFI offline.11 Additionally, more than 10 percentage points decrease of LVEF to a value lower than the lower limit of normality was considered significant reduction.9Echocardiography variables included LV systolic function, LV end systolic volume (LVESV), LV end diastolic volume (LVEDV), LAVI, fractional shortening, E, A, E/A, (TAPSE), global, regional as well as segmental LPSS, global LPSS, segmental LPSS including apical, mid LPSS, and basal LPSS, as well as segmental LPSS for each of the 17 segments  were evaluated prior and after treatment with anthracycline chemotherapy. A relative reduction of more than 15% in global LPSS between pre- and post-chemotherapy values was considered clinically significant according to the published expert consensus.®, Chicago, IL). Categorical variables were presented as frequencies and percentage, while continuous data were expressed as mean and standard deviation. Continuous variables were checked for normality of distribution by Kolmogorov-Smirnov. Fisher’s exact test was used for comparison of categorical variables. Continuous variables were compared by paired t test. Pearson’s correlation coefficients were used to explore correlation between LVEF and global and segmental LPSS. P value of ≤0.05 was considered statistically significant.The collected data were analyzed by SPSS version 22.0  had grade I diastolic dysfunction (E/A < 0.75) and 4 patients (6%) had reduced RV systolic function (TAPSE < 16). In 39 patients (62%) LAVI was normal, and the rest had mild LA enlargement. P = 0.006) and fractional shortening decreased to 30.4 ± 6.5% (P = 0.015). P = 0.013) and basal (P = 0.031) segments, but no significant difference was observed in other segments following chemotherapy when compared to pre-chemotherapy results. Pair-wise comparison of changes in strain of global and each segment of the left ventricle before and after chemotherapy is shown in After chemotherapy, mean LVEF decreased to 56.6 ± 8.2% , based on the longitudinal 2D strain echocardiography results, eight patients (13%) showed a significant reduction in global LPSS. Moreover, the assessment of longitudinal 2D-strain of apical segments, in 18 cases (28.6%), mid segments, in 10 cases (16%) and basal segments, in 17 cases (27%) demonstrated significant reduction (>15% relative decrease). Significant reductions in the 89 out of 315 apical segment (28%), 117 out of 378 mid segments (31%) and 141 out of 378 basal segment (37.3%) were noted. Assessing all 17 segments in 63 recruited patients  indicated a significant reduction in 347 (32%) segments. One patient (1.6%) required hospitalization for treatment of acute heart failure. This particular patient had a LVEF of 35% and reduction in her global LPSS from -23% to -11%.Additionally, the correlation of percentage changes in regional and global LPSS and changes in LVEF the respective baseline values were evaluated and is shown in 12 Additionally, Doppler echocardiography was suggested to be a useful tool for determination of the hemodynamic status, especially when increased pulmonary arterial pressure is suspected. In the study published by Tassan-Mangina et al in 2006, 20 patients receiving doxorubicin were examined by echocardiography before, 1-3 months and 3-5 years after chemotherapy. In this study late reduction LVEF despite an initially normal values was commonly reported after anthracycline therapy.13 Subtle changes in myocardial performance may not be readily identifiable by LVEF. Moreover, the difficulty of LV afterload assessment by echocardiography adversely affects specificity of LVEF. Considering these limitations, 2D strain echocardiography has gained popularity for early detection of cardiotoxicity associated with chemotherapy. Jurcut et al introduced the application of strain rate imaging for timely detection of subtle myocardial injury in a study performed on 16 patients undergoing anthracycline therapy.14 It has been suggested that the changes in strain could be regional and segmental, though this has been a matter of controversy.15 According to the recommendations, modified Simpson method is the preferred method for measuring LVEF on two-dimensional echocardiography. In this recommendation calculation of LVEF is to be combined with the wall motion score index.16Anthracyclines and relevant compounds are among the most common causes of drug-induced cardiotoxicity and timely recognition of myocardial damage in patients receiving these agents is essential. Yeh et al introduced echocardiography as a useful non-aggressive alternative method for the assessment of heart function and diagnosis of cardiotoxicity caused by administration of anthracyclines.16 Regional wall motion abnormalities particularly in the apical segments in patients receiving anthracycline treatment have been recognized for a long time.17 In one study on pediatric population, regional changes in basal, and mid sections and basal anterolateral, mid anterior, mid inferior, segments were reported.10 Additionally, segmental reductions in LPSS in mid and apical segments were found to have a reasonable predictive value for reduction of LVEF in follow-up.10 In another study on 52 women with breast cancer significant reductions of LPSS was noted in all but apical lateral segment in the echocardiography exam performed 1 week after termination of anthracycline chemotherapy.7 In accordance with our findings, these authors have also pointed out the possibility of regional heterogeneity in the development of myocardial dysfunction, though the technical limitation pertinent to image quality could have also contributed to this observation.7Wall motion score index measurement based on the 17-segment model is considered to be a more sensitive method when compared to LVEF for evaluation of the extent of injury induced by anthracyclines. Likewise, myocardial deformation can be measured through Doppler tissue imaging or 2D Speckle tracking echocardiography.10 However, we identified patients in whom despite a decrease in LVEF, global longitudinal peak systolic strain failed to show any significant changes. We observed that these patients had higher heart rates in the second exam. We also noticed that these patients had significant strain reduction in several segments yet their effect might have been offset by the changes in LPSS of other segments in the opposite direction. We assume that global LPSS may not be influenced if the reduction of LPSS in some segments is accompanied by an increase in the value in other segments. For further evaluation, we did a correlation analysis and we observed that changes of LPSS in mid papillary region has the highest correlation with the global LPSS. The contribution of each segment to the global LPSS may not be equal and as such involvement of various segments/regions could translate to dissimilar effects on global value of LPSS. As such, in these cases global LPSS of these patients could be normal, which highlights the need for not only global but also a segmental assessment of the values. This is consistent with the histologic reports of scattered focal myocardial fibrosis in these patients.18 We acknowledge that this observation could be due to the presence of tachycardia following chemotherapy. Higher heart rates can adversely affect the clarity of endocardial borders in certain views and therefore, measurement errors are more likely to happen.In accordance with previous studies, we also report that longitudinal 2D-strain echocardiography, is a valuable tool in diagnosis of anthracycline-induced toxicity.In the present study, the conventional and longitudinal 2D-strain echocardiography methods were used to examine the toxic effects of anthracyclines. The results of longitudinal 2D-strain echocardiography were not significantly influenced by the presence of diabetes or hypertension. Significant LPSS reduction was detected in the basal anteroseptal and all-basal segments, but no significant difference was observed in other segments. Additionally, segmental changes were observed in patients with no reduction of global LVEF, which denote the presence of a regional pattern in the occurrence of myopathy.We conclude that the longitudinal 2D-strain echocardiography findings obtained before and after chemotherapy indicate a segmental pattern in myocardial dysfunction. 2D-strain echocardiography is a useful tool for timely diagnosis of myocardial dysfunction, though global assessment may be subject to limitations. Considering the observed regional pattern in myocardial involvement, segmental evaluation of longitudinal peak systolic strain might be a more accurate way of detecting early myocardial dysfunction. Further studies enrolling larger number of patients supplemented with histo-pathological evidences are much anticipated.The study is limited by the relatively small sample size and lack of long-term follow-up. Additionally, the definition of significant decrease of >15% has been proposed for global LPSS. Accordingly, since correspondent values for each segment has not been validated the assumption might not necessarily hold true for segmental or regional values. Furthermore, a single echocardiographist performed all the measurements and we have not evaluated the intra-observer variability.The authors declare that they have no competing interests.Institutional review board and ethics committee approved the study protocol.We would like to express our sincere thanks to Dr. Soheyla Nazarnia, and Ms. Maryam Ghahremani Nasab for their invaluable helps with data collection and editing the paper.


Cor triatriatum is a rare congenital heart defect that is associated with an increased risk for developing atrial fibrillation. We report a case of a healthy 38-year-old man who presented in decompensated heart failure and atrial fibrillation with a rapid ventricular response. A transthoracic echocardiogram (TTE) demonstrated severe biventricular dysfunction and dilatation in addition to cor triatriatum sinister. He was diuresed with resolution of his symptoms and spontaneously converted back to sinus rhythm. There is limited evidence in the literature surrounding anticoagulation and associated left ventricular dysfunction in the setting of cor triatriatum which posed difficult therapeutic decisions. Cor triatriatum sinister is a rare congenital defect in which the left atrium is divided into two chambers by a membrane. Cor triatriatum comprises approximately 0.4% of congenital heart disease at autopsy . It is fA previously healthy 38-year-old man, who had emigrated from Honduras 5 years ago, presented with a several weeks history of progressive abdominal pain and dyspnea. Physical examination revealed respiratory distress, an irregularly irregular tachycardia at 140 beats per minute, and a blood pressure of 126/72 mmHg. The cardiac exam was remarkable for a displaced and diffuse apical beat, and a 2/6 mitral regurgitation murmur heard at the apex. His ECG demonstrated atrial fibrillation (AF) with a rapid ventricular response. There was no electrocardiographic evidence of right ventricular overload. Chest X-ray showed cardiomegaly and pulmonary edema. Transthoracic echocardiography (TTE) demonstrated a markedly dilated left atrium in the four-chamber view (51 mm) divided into 2 chambers by a membrane . ContinuThe patient was admitted and diuresed. He spontaneously converted to sinus rhythm and remained free of AF at discharge. Given the coexistence of AF and cor triatriatum sinister, the decision was made to initiate anticoagulation with heparin with subsequent conversion to warfarin. The workup of alternative causes of his dilated cardiomyopathy (including serology for Chagas and autoimmune disease) proved to be negative. In addition, there was no history of significant alcohol intake. At 3 months follow-up, he remained in sinus rhythm and had returned to functional class 1 despite lack of improvement in LV systolic function on focused cardiac ultrasound evaluation.Cor triatriatum sinister is a rare congenital malformation involving an abnormal membrane dividing the left atrium into two chambers. It is thought to arise from failure to resorb components of the common pulmonary vein during embryogenesis . The mosGiven the rarity of the diagnosis, formal guidelines do not exist on the optimal timing of surgical correction. Surgery has typically been offered in symptomatic adults . In the This case posed several unique diagnostic and therapeutic challenges. The etiology of dilated cardiomyopathy in this gentleman was not entirely clear. The initial suspicion was that the cardiomyopathy was secondary to uncontrolled tachycardia. This was challenged by the persistently depressed ejection fraction at 3 months follow-up despite apparent maintenance of sinus rhythm, and therapeutic doses of a beta blocker and ACE inhibitor. The workup for alternative etiologies had been negative, and no additional cardiac congenital abnormalities were discovered. Cor triatriatum has rarely been described in association with left ventricular failure, but in the setting of an additional insult such as pregnancy . There iCardioembolic stroke has been reported to occur with cor triatriatum with and without concurrent atrial fibrillation , and it Cor triatriatum is a rare but increasingly recognized congenital abnormality that can become symptomatic later in life. It is associated with the development of atrial fibrillation, pulmonary hypertension, and rarely with the development of left ventricular dysfunction. As access to imaging modalities and the quality thereof improve, more data will be needed to guide treatment decisions around thromboembolic prophylaxis and follow-up to prevent complications.


To quantitatively evaluate the clinical value and demonstrate the potential benefits of biochemical axial T2∗ mapping-based grading of early stages of degenerative disc disease (DDD) using 3.0-T magnetic resonance imaging (MRI) in a clinical setting.Fifty patients with low back pain and 20 healthy volunteers (control) underwent standard MRI protocols including axial T2∗ mapping. All the intervertebral discs (IVDs) were classified morphologically. Lumbar IVDs were graded using Pfirrmann score (I to IV). The T2∗ values of the anterior annulus fibrosus (AF), posterior AF, and nucleus pulposus (NP) of each lumbar IVD were measured. The differences between groups were analyzed regarding specific T2∗ pattern at different regions of interest.P < .01). The T2∗ value of the anterior AF was not significantly different between the patients and the controls (P > .05). The mean T2∗values of the lumbar IVD in the patient group were significantly lower, especially the posterior AF, followed by the NP, and finally, the anterior AF. In the anterior AF, comparison of grade I with grade III and grade I with grade IV showed statistically significant differences . Similarly, in the NP, comparison of grade I with grade III, grade I with grade IV, grade II with grade III, and grade II with grade IV showed statistically significant differences (P < .001). In the posterior AF, comparison of grade II with grade IV showed a statistically significant difference (P = .032). T2∗ values decreased linearly with increasing degeneration based on the Pfirrmann scoring system .The T2∗ values of the NP and posterior AF in the patient group were significantly lower than those in the control group (Changes in the T2∗ value can signify early degenerative IVD diseases. Hence, T2∗ mapping can be used as a diagnostic tool for quantitative assessment of IVD degeneration. Degenerative disc disease (DDD) is regarded as the most prevalent cause of LBP, even though the pathophysiological correlations between pain and disc degeneration are not fully understood as LBP is multifactorial. Ogon et al analyzed the relationship between the T2 values of degenerative IVD and chronic LBP, and they noted a correlation between posterior annulus fibrosus (AF) degeneration and chronic LBP.Low back pain (LBP) is one of the most common musculoskeletal disorders. In the elderly population, its incidence is up to 60% to 80%, resulting in a huge burden to the community.,10 Currently, MRI is the preferred method for examining and diagnosing IVD degeneration, soft tissue degeneration, and nerve injury. Because of advantages such as lack of radioactivity, high resolution, multiparameter, and multi-azimuth image output. However, it also has some limitations: a long scanning time, and it being prone to motion artifacts. Early changes in the structure cannot be measured by standard MRI sequences. Another limitation of today's standard MRI protocols is the poor distinction of the nucleus–annulus interface. Meanwhile, in degenerative IVDs, the distinction of NP and AF may be difficult to evaluate or may even be completely lost in end-stage DDD. The detection of early degeneration is also dependent on the visualization of biomechanically important structures. For example, Thompson et al described the mucinous infiltration of the AF and a loss of fibre orientation of the inner annulus as some of the earliest signs of disc degeneration. Researchers have recently shown an increased interest in methods that quantify IVD biochemical composition.,14The AF of the IVDs is mainly composed of fibro-cartilage; which has a fibrous structure and low water content and functions as a rigid containment for the nucleus pulposus (NP). The gelatinous structure of the NP, however, consists mostly of water, with a low yield of collagenous material. IVD degeneration occurs when disc cells cannot maintain a highly hydrated proteoglycan-rich matrix for the NP and when the collagen structure is lost, which affect the mechanical integrity of the IVD.,15 T2∗ has also proven to be a reliable and valid method for biochemical cartilage imaging, and a few studies implied a close relationship with T2. Determining the onset of degeneration at the earliest possible stage is crucial for the success of regenerative IVD treatment, and T2∗ appears to be an adequate diagnostic method that can be implemented into a clinical MR protocol.T2∗ mapping is an imaging technology based on MR that has the advantages of fast imaging speed, high resolution, and 3-dimensional evaluation of IVD homogeneity and it has been widely used in recent years at home and abroad to examine the degeneration of knee joint ligaments, spinal cord, and articular cartilage degeneration.We analyzed the T2∗ values of the IVDs between the volunteers and patients with LBP, and explored the feasibility and value of quantitative analysis of IVDs degeneration by MR T2∗mapping imaging. Furthermore, to correlate our results with already existing clinical score with the goal to assess the capability of T2∗ mapping as a diagnostic technique on clinic.22.1Institutional review board  of the First Affiliated Hospital of Nanchang University approval was obtained before the examination of patients and volunteers. All subjects consented to participate in this study.Inclusion criteria: patients with LBP over 6 months; age over 18 years. Volunteers were included that they had no symptoms on the VAS . Exclusion criteria : the lumbar tuberculosis, lumbar IVD infection, blood disease involving the lumbar spine; severe lumbar hypoplasia; the rheumatism and rheumatoid immune system disease; the lumbar spinal tumors; a history of trauma or surgery or lumbar spondylolisthesis or lumbar fracture patients; spine ankylosis; MRI examination revealed abnormal signal in lumbar paraspinal muscle and sacroiliac joint lesions in patients; the metal implants, and contraindication for MRI examination.Levenet test for analyzing the patients T2∗ value, and the variance was previously checked for homogeneity.In this study, a total of 350 discs were scanned, and the IVDs were clearly displayed on the gradient echo images and T2∗mapping. An one-way analysis of variance (ANOVA) used 2.2Magnetic resonance imaging was performed on a 3.0 Tesla whole-body MR unit  using a dedicated 8-channel spine coil . All imaging was performed in the supine position, told the patients keep calm breathing, as far as possible to maintain the waist still. Morphological evaluation of IVD with axial T2-weighted images (T2WI). T2∗ mapping axial scanning, fast spin echo (FSE) sequence: repetition time (TR) 575 mses, echo time (TE) 4.2, 11.3, 18.5, 25.6, 32.7 milliseconds, field of view (FOV) 160 × 160 mm, voxel size 0.4 × 0.4 × 4.0 mm, interslice gap 0.3 mm, number of slices 15, examination time 3 minutes 41 seconds. It consists of 5 lumbosacral segments (L1/2∼L5/S1). Each segment is scanned in 3 slices, and the scanning direction is parallel to transverse plane of the IVD.2.3All images were graded by an experienced radiologist (15 years of experience with MRI) and an experienced orthopedic spine surgeon  in consensus. All observers have experienced in musculoskeletal MRI regions of interest (ROI)selection . Moreover, observers A and B repeated the same analysis to evaluate intraobserver agreement 1 month apart independently. Observers graded strictly according by the improved Pfirrmann IVD degeneration grading standard  used by hand tools: draw a rectangle ; the remain part of nucleus pulposus (NP) draw a circle with diameter of 60% the whole length. The raw data upload to the A Tim System Workstation, copied to the corresponding T2∗ maps  of patients, and volunteers. The χ2 test applied to the sex of patients versus volunteers; one-way ANOVA was used to compare the T2∗ values of IVDs of patients and volunteers (Modified Pfirrmann grading). The consistency the data of observers A and B who drew the ROI were analyzed by independent sample t test and the intrarater reliability analysis. Correlations between variables were analyzed for statistical significance using Spearman's rho coefficients. Correlations were considered strong for ρ > 0.7, moderate for 0.5 <  ρ < 0.7, and weak for ρ < 0.5; All statistics were done with SPSS version 23.0 . P < .05 was taken as statistically significant.Descriptive statistical data are given as mean ± standard deviation (SD) (x ± s). The data with the normal-like distribution and homogeneity of variance, a 2-tailed 3P = .236). The mean BMI was 23.1 ± 3.3 kg/m2 (range 17.7–33.2) in the patient group and 22.2 ± 2.1 kg/m2 (range 17.5–25.0) in the volunteer group (P = .282), and the gender was also no statistically significant differences in the 2 group (P = .939). Here, there were no statistically significant differences in age, BMI, or sex between patient group and volunteer group (P > .05). The intrarater reliability analysis of observers A and B who drew the ROI: anterior AF: t = 1.522, P = .658, Cranbach α=0.969; NP: t = –0.994, P = .961, Cranbach α=0.977; posterior AF: t = –4.043, P = .961, Cranbach α=0.952.In our study, we selected 50 patients and 20 volunteers from May 2015 to April 2016 in the First Affiliated Hospital of Nanchang University. A total of 50 patients  and 20 volunteers  were included in the study. The mean age was 45.5 ± 9.9 years (range 25–66 ys) in the patient group and 35.6 ± 7.5 years (range 24–47 ys) in the volunteer group (3.1P < .01); there were no statistically significant difference in anterior AF T2∗ values between patients and volunteers (P = .511)  and volunteers  were used by one-way omnibus ANOVA for statistical analysis. The results showed: the T2∗ values of the NP and posterior AF in patient group were significantly lower than in healthy volunteer group  found 78 (31.2%) grade I; 79 (31.6%) grade II; 34 (13.6%) grade III; 59 (23.6%) grade IV. No discs were graded as Pfirrmann 8.3.2.1Levene statistic = 4.163, P = .007, not homogeneous, so the T2∗ values were analyzed by Dunnett T3 test. There were statistically significant differences in the anterior annulus fibrosus when grade I versus grade III (P = .07) and grade I versus grade IV (P = .08). . (Table The results showed that the NP: ). Table .3.2.3Levene statistics = 2.559, P = .056 (P > .05), was homogeneity, so the T2∗ values of the posterior AF were analyzed by LSD test. There was only significant difference when grade II versus grade IV (P = .032). (Table The results showed that the posterior AF: 3.3P < .001). Correlations between T2∗ value and other outcome parameters in the AF were weak and did reach statistical significance .The correlation between T2∗ mapping in the ROI and Pfirrmann score is shown in Figure 4 Other studies already have showed that quantitative sagittal T2 mapping shows significant differences between herniated disc and annular tears compared with discs without pathological abnormalities–23 and quantitative sagittal T2∗ was shown to be more sensitive in depicting changes in the AF compared with normal T2 sequences. And other scholars have held a certain correlation between the T2∗ and T2 values.,26 The T1rho imaging was also studied by some scholars. But it has some advantages and disadvantages. Its advantages are mainly: also sensitivity for early cartilage damage; reported correlation with radiographic cartilage damage, joint pain, and functional impairment. And its disadvantages are mainly difficult to implement in clinical/ research routine; requires high field strengths and high RF pulse energy levels; affected by cartilage orientation within main magnetic field.,27 Because the T1rho imaging has certain limitation , so it is less applied clinically. In recent years, researchers at home and abroad have been used MRI T2∗ mapping for the early diagnosis of articular cartilage and endplate lesions. However, only a few obtained cross-sectional the T2∗ mapping image.In this study, we investigated a MRI method, applicable for conventional 1.5 or 3.0-Tesla units, for axial T2∗-weighted mapping of IVDs that can be used in a clinical setup. The benefits of T2∗ mapping as a routine technique for biochemical and structural analysis of cartilage tissue, not only on the spine but also on other joints, such as the hip, knee, and ankle, have been confirmed by other publications.,29 Therefore, our hypothesis was that axial T2∗ mapping can be a promising technique in showing early stages of disc degeneration in all areas of the IVD.Compared with sagittal-oriented imaging methods, axial mapping allows the examination of a larger disc area and has been shown to be a useful grading instrument, especially, during early stages of disc degeneration. but the change in the T2∗ value is caused by a change in water content, collagen fiber disorder and loss of some biochemical macromolecules such as proteoglycans. Therefore, determining early changes in IVD through imaging can lead to early diagnosis, treatment and prevention of IVD degeneration.The degeneration of the IVD mainly involves cartilage destruction, In this study, we selected the central IVD slice (slice 2 of 3) for T2∗ values evaluation of IVD, and our techniques were based on the latest literatures and research methods at home and abroad. Some scholars have demonstrated that early IVD degeneration mainly involves changes in the NP, such as the decreased water content and collagen changed.A study has stated that, in adults, proteoglycans accounted for about 50% and 10∼20% of the dry weight in the NP and AF, respectively, and collagen accounts for about 15∼20% and 65∼70% of the dry weight in NP and AF, respectively. found a strong relationship between the change in IVD biochemistry and the T2∗ value. The related degree of IVD tissue collagen is even higher than the Pfirrmann grade. Hence, MRI T2∗ has big potential for reflecting early IVD degeneration, and the diagnosis of IVD degeneration also outweighs its morphology grading. The disc Pfirrmann classification is generally based on disc height and signal intensity, as visualized in T2-weighted images, which shows the changes in morphology and water content that occur in IVD degeneration. Thus, it became a common clinical method for evaluating and quantifying IVD degeneration. We classified IVD according to the modified grading of Pfirrmann score: grade I, Pfirrmann 1; grade II, Pfirrmann 2 to 4, based on the signal of the NP and inner AF; grade III, Pfirrmann 5; grade IV, Pfirrmann 6 to 8, based on disc height loss. However, none in the patient group had a Pfirrmann score of 8. This modification was done mainly to reduce subjective evaluation errors and also to highlight the differences in the classification.Auerbach et al,31 The mean T2∗ values of the regions of interest—the anterior and posterior AF and the NP of the IVD—were obtained . This demonstrates that the T2∗ value was very sensitive to IVD degeneration, which is mainly associated with NP changes, furthermore, the T2∗ value hints at the degree of disc degeneration. The results showed a certain correlation between the T2∗ value of lumbar IVD and the Pfirrmann classification. Hoppe et al obtain T2∗ mapping cross-sectional images of 93 patients with lumbar disease using 1.5 T MRI, and quantitatively evaluated the integrity structure of lumbar IVD. Their findings proved that T2∗ mapping is effective in detecting early IVD degeneration, which can be used to evaluate and grade spinal diseases. The above results are consistent with those of our study. From the perspective of the mechanism of MR T2∗ mapping imaging, the T2∗ value mainly reflects the water content, cartilage composition and collagen structure. If these components are increased, then the T2∗ value is increased, and vice versa. When the IVD is severely degenerated, however, the amount of water in the disc is lost, the cartilage and collagen structure is disordered, or even destroyed, and thus, the T2∗ value is reduced. However, early degeneration can also cause a change of T2∗ value. The change can be attributed to the secretion of inflammatory cytokines and related proteins during the early stages of inflammation, which can lead to an increase in the composition of the disc such as moisture and protein in the NP, in turn leading to higher T2∗ values.To better reflect the overall morphological IVD, and effectively reduce the interference to the results of the T2∗ value for volume effect. The measurement method was based on related literature. Therefore, direct correlation between the T2∗ value and the actual condition of the IVDs was not possible. Notably, however, we did not encounter severe limitations due to susceptibility artifacts.The main reason for error is possibly the subjective grading by physicians and unclear images of the early IVD degeneration, which could have contributed to the limitations of this study. Furthermore, the sample number is small and the poor consistency of the Pfirrmann classification of lumbar IVDs. A major limitation is the lack of histological or biochemical analysis of IVDs.In conclusion, axial T2∗ mapping is feasible method for detecting early stages of DDD. As many patients with LBP have no abnormal signal in IVD imaging, the T2∗ value, obtained through MRI T2∗ mapping, can be predict and evaluate the degree of lumbar disc degeneration. Furthermore, this technology can be used to formulate the classification criteria for the diagnosis of IVD degeneration, paving the way for standardization and digitization [What do you mean by digitization? Do you mean an objective imaging technique that can be used for diagnosis?] and its clinical application in the diagnosis and treatment of such diseases.


Myocardial T1, T2 and T2* imaging techniques become increasingly used in clinical practice. While normal values for T1, T2 and T2* times are well established for 1.5 Tesla (T) cardiovascular magnetic resonance (CMR), data for 3T remain scarce. Therefore we sought to determine normal reference values relative to gender and age and day to day reproducibility for native T1, T2, T2* mapping and extracellular volume (ECV) at 3T in healthy subjects.After careful exclusion of cardiovascular abnormality, 75 healthy subjects aged 20 to 90 years old  underwent left-ventricular T1 (3-(3)-3-(3)-5 MOLLI)), T2 (8 echo- spin echo-imaging) and T2 * (8 echo gradient echo imaging) mapping at 3T CMR (Philips Ingenia 3T and computation of extracellular volume after administration of 0.2 mmol/kg Gadovist). Inter- and intra-observer reproducibility was estimated by intraclass correlation coefficient (ICC). Day to day reproducibility was assessed in 10 other volunteers.p < 0.05) and ECV , but not T2  were significantly greater in age matched women than in men. T1  and ECV  increased, while T2 decreased significantly  with increasing age. T2* was not influenced by either gender or age. Intra and inter-observer reproducibility was high (ICC ranging between 0.81-0.99), and day to day coefficient of variation was low .Mean myocardial T1 at 3T was 1122 ± 57 ms, T2 52 ± 6 ms, T2* 24 ± 5 ms and ECV 26.6 ± 3.2%. T1 (1139 ± 37 vs 1109 ± 73 ms, We provide normal myocardial T2, T2*,T1 and ECV reference values for 3T CMR which are significantly different from those reported at 1.5 Tesla CMR. Myocardial T1 and ECV values are gender and age dependent. Measurement had high inter and intra-observer reproducibility and good day-to-day reproducibility. Cardiovascular magnetic resonance (CMR) myocardial tissue mapping techniques become more and more widely used in clinical practice. Indeed, they allow to pixel wise measurement of T1, T2 and T2* time constants in the heart and offer new opportunities for non-invasive identification of various cardiac infiltrative pathologies . T2 mappWhereas normal values for T1, T2 and T2* times are well established for 1.5 Tesla (T) CMR , 10–15, The protocol was approved (#2014/19NOV/577 ‘VAL REF’) by the IRB of the Cliniques St. Luc UCL Brussels, Belgium and subjects were included after giving written informed consent to participate in this study. Healthy asymptomatic volunteers of different age groups (about 10 per decade) aged between 20 and 90 years were screened by advertisement in the local community. Prior to inclusion and CMR, all subjects underwent a clinical exam and assessment of medical history and cardio-vascular risk factors ie smoking (active smoking or history of >5UAP), hypertension (systolic and diastolic blood pressure > 140/90 mmHg during home controls or treatment), hypercholesterolemia (cholesterol >190 mg/dl or/and LDL cholesterol >115 mg/dl), history of familiar cardio-vascular disease (acute coronary syndrome or coronary revascularization in first degree relatives < 65 years old) and obesity (BMI > 30 kg/m2). All subjects underwent rest and stress ECG, 2D echocardiography and blood sampling with measurement of GFR (MDRD formula), hematocrit, cholesterol and NT-proBNP prior to inclusion.Exclusion criteria were 1) any evidence of heart disease as indicated by clinical history, physical exam, atrial fibrillation, presence of abnormal rest or stress ECG or presence of abnormal cardiac function or valve disease at the echocardiography; 2) pregnancy; 3) contra-indications to CMR , or to injection of gadolinium (Gd) based contrast agent  and 4) diabetes.Scan-rescan reproducibility of pre-, post- T1, T2 mapping, T2* and ECV was performed in 10 additional healthy subjects  who underwent identical CMR exams on two consecutive days.CMR was performed using a 3 Tesla system . To assess left ventricular (LV) myocardial function and mass, 12 consecutive 10 mm short-axis images and 2-, 3- and 4-chamber long axis image of the LV were acquired using a cine balanced steady state free precession sequence (bSSFP). Then, one mid-ventricular short axis and one 4 chamber Modified look locker (MOLLI) images were acquired for T1 determination using an 11 image, 17 heart-beat 3-(3)-3-(3)-5 bSSFP sequence . Imaging3 gadobutrol were infused as bolus pushed by a 15 cm3 saline at 3 cm3/s, 15 s later, the remaining contrast dose followed by 20 cm3 saline were infused at a slower rate of 1 cm3/s. Ten minutes after contrast injection, short- and long-axis 2D inversion recovery late gadolinium enhancement (LGE) images were acquired with an inversion-recovery gradient-echo imaging sequence to evaluate focal myocardial fibrosis. Finally, post-contrast MOLLI T1 mapping was repeated in identical prescription as pre-contrast T1 mapping, 12 min after gadolinium injection. This time was consistent across subjects.Then, a total dose of 0.2 mmol/kg gadobutrol  was injected in a 2 phase protocol: 3 cmCMR images were anonymized and analyzed in double by two experienced observers (CR and AS with 3 years of CMR experience and level 2 Euro-CMR certification) blinded to clinical data.http://segment.heiberg.se)  if not normally distributed; categorical variables were reported as counts and percentages. All tests were 2 sided and 2 or exact test. Continuous variables were compared among groups using ANOVA when normally distributed, else using Kruskall-Wallis test. Individual differences among groups were compared post-hoc using Mann-Whitney U tests (with Bonferroni correction for multiple comparisons) for non-normally distributed data and Tukey-Kramers test for normally distributed data with equal variances. Differences between 4 chamber and short-axis T1 and ECV were measured using paired T test. Relations of T1, T2 and T2* times and ECV with age were compared using Pearson’s correlation coefficient. Male and female subjects were matched for age thanks to a propensity score (1:1) with a caliper of 0.25 standard deviations of the propensity score, using the STATA 10.0 software  and the psmatch routine. Uni and multiple regression analysis was used to assess the effects of clinical characteristics on T1 times, ECV, T2 mapping and T2* times. Intra and inter observer and day-to-day reproducibility of T1 T2 T2* times and ECV were assessed with an intraclass correlation coefficient and using coefficient of variation (SD/Mean).Subjects were categorized into different decades. Categorical variables of subjects in different age groups were compared using χSeventy six healthy subjects were screened, 1 was excluded due to presence of diabetes. The final population consisted of 75 participants. The baseline characteristics of the 75 subjects are shown in Table The CMR protocol was successfully completed in all subjects. All participants had normal cardiac function and no focal scar on LGE images.Artifacts precluded analysis of native T1 in 1 patient and of post contrast T1 maps in 2 subjects, resulting in missing ECV in 3 subjects. T2 and T2* maps were not analyzable due to artifacts in 1 subject.Normal CMR reference values of the 75 subjects according to decade age groups are shown in Table 2 vs. 25 ± 3 kg/m2, p = 0.002 and 1.66 ± 0.11 m2 vs. 1.93 ± 0.13 m2, p < 0.001 respectively), lower hematocrit  but no significant difference in cardiovascular risk factors or ferritin level. By CMR, females had lower indexed LV mass, lower indexed LV and RV end-diastolic volume and lower mass/volume ratio than males. LV and RV ejection fraction were similar. Native T1 septal times  and ECV were significantly higher in women than in men. Whole T2 times and T2* were not different. Native blood , but not myocardial T1 times  were weakly correlated to hematocrit.Using propensity score matching, 28 male and female subjects were matched for age. Sex related differences of CMR parameters are shown in Table Multivariate regression models correcting T1, T2 and ECV values for Age and sex are shown in Table p = 0.40 and p = 0.73 respectively).For 32 subjects, native T1 time and ECV were compared in a septal ROI in a short axis and a 4 chamber views. The mean 4C native T1 times and ECV were 1158 ± 80 ms and 27.4 ± 3.6% respectively. Both were non-significantly different from values obtained in the septum in the SA view -3-(3)-5 Molli schemes, causing underestimation of T1 values at higher heart rates. MOLLI schemes ensuring full recovery between inversion pulses such as 5 s-(3 s)-3 s might provide more accurate T1 estimation at 3T and high heart rates, but were not yet available in our study. Since we observed a non-significant trend for increase rather than decrease of T1 at higher heart rate, we do not believe that this effect may have significantly affected our results. Also, we employed 35° flip angle which is the standard at 1.5 T, while others used 20° at 3 T, and this might introduce reproduciblilty issues. In our study, standard deviation of native T1, T2 and ECV values were somewhat larger than those previously reported. Since we found that these values are age dependent, this may be explained in part by wider age range of our population. Other possible explanations are reduced B0 and B1 field homogeneity at 3T then at 1.5 T. For T1, the larger variation may also be explained by the overall higher T1 values at 3 T. Also ECV values were determined after 0.2 mmol/kg gadubutrol, and slightly lower ECV values have been reported when lower doses of contrast media were injected.Finally for day to day reproducibility of ECV, hematocrit values were sampled only once. Potential physiological day to day variation of hematocrit values were not thus not taken into account in the day-to-day variability of these measurements.We report specific normal myocardial T1, T2, T2*, and ECV reference values for 3T CMR to facilitate interpretation of CMR mapping techniques at this field strength. We demonstrate that measurements values at 3T were significantly different from those reported at 1.5 Tesla. Furthermore we found that T1 and ECV were age and sex dependent, while T2 was age dependent pnly, suggesting that it is necessary to adjust for age and sex when interpreting normal ranges of T1, T2 and ECV values for clinical CMR examination. Finally we demonstrated high inter- intra- and particularly day- to day- reproducibility of these measurements, indicating the ability of serially following these parameters over time.


The aim of this review is to highlight recent advancements, current trends, and the expanding role for cardiac CT (CCT) in the evaluation of ischemic heart disease, nonischemic cardiomyopathies, and some specific congenital myocardial disease states.CCT is a highly versatile imaging modality for the assessment of numerous cardiovascular disease states. Coronary CT angiography (CCTA) is now a well-established first-line imaging modality for the exclusion of significant coronary artery disease (CAD); however, CCTA has modest positive predictive value and specificity for diagnosing obstructive CAD in addition to limited capability to evaluate myocardial tissue characteristics.CTP, when combined with CCTA, presents the potential for full functional and anatomic assessment with a single modality. CCT is a useful adjunct in select patients to both TTE and CMR in the evaluation of ventricular volumes and systolic function. Newer applications, such as dynamic CTP and DECT, are promising diagnostic tools offering the possibility of more quantitative assessment of ischemia. The superior spatial resolution and volumetric acquisition of CCT has an important role in the diagnosis of other nonischemic causes of cardiomyopathies. Cardiovascular disease remains the worldwide leading cause of morbidity and mortality accounting for up to 31% of all deaths , 3. NumeTransthoracic echocardiography (TTE) is the most widely available and commonly used technique for assessing cardiac structure and function. However, TTE assessment may be suboptimal in certain subsets of patients, namely those with poor imaging windows due to lung disease, obesity, chest wall defects, or overlying dressings in burn and post-surgical patients. CMR imaging is a powerful adjunctive test in these patients and is the current gold standard for assessment of cardiac volumes and systolic function. Compared with TTE and CMR, CCT has superior spatial resolution with decreased but comparable temporal resolution , 10. QuaMyocardial assessment in ischemic heart disease encompasses both the anatomical assessment of the cardiac dimensions and structure as well as indirectly assessing coronary artery stenosis severity and CAD chronicity. There is a complex interaction between observed coronary anatomy  and the presence of ischemia. Published data demonstrates that a luminal stenosis ≥ 50% by CCTA correlates poorly with myocardial ischemia by either single-photon emission computed tomography (SPECT) or positron emission tomography (PET) with positive predictive value (PPV) ranging from 29 to 58% . ConversThe last decade has witnessed a shift in the diagnostic approach for ischemic heart disease away from the utilization of a single functional testing modality followed by ICA to a patient-centered multimodality approach. This approach takes into account patient parameters, preferences, and radiation dose considerations to guide therapy. As such, providers tasked with the evaluation of ischemic heart disease need a baseline understanding of the strengths and limitations of available modalities to allow for a multimodality imaging approach to these patients.SPECT is a static imaging modality that leverages differential distribution and uptake of modest energy 70–120 keV) radiotracers within the myocardium based on differences in coronary blood flow and myocardial viability. SPECT imaging, compared to iFFR, has a sensitivity of 74% and specificity of 79% for the diagnosis of significant obstructive CAD  keV radi, 22. ObePET is a versatile nuclear imaging modality that detects high-energy (512 keV) photons that result from an annihilation interaction between a positron and a valence electron. In addition to static perfusion data, the radiotracers Rb-82 and 13N-ammonia can be used to quantify absolute coronary blood flow and coronary flow reserve , 30. ViaCMR is the gold standard for the assessment of cardiac structure and function. Additionally, with emerging applications such as T1 mapping, CMR is the best validated noninvasive modality for tissue characterization. The addition of intravenous gadolinium allows for both first-pass stress imaging, utilizing gradient echo sequences, for the assessment of myocardial ischemia , 33. ComCCT is an emerging application with the potential to deliver coronary anatomy and functional significance in a single scan. Utilizing vasodilator stress agents, CCT is able to assess differences in myocardial distribution of iodinated contrast, a technique referred to broadly as cardiac CT perfusion (CTP) •. CTP prCTP relies on the kinetic properties of iodinated contrast as it is distributed and taken up into myocardial tissue. CTP imaging involves rest and stress acquisitions and can be performed in a static or dynamic method. Figure Rest first, followed by stress image acquisition protocol, is the most widely used in clinical practice and is best suited for low- to intermediate-risk patients without known CAD Fig. a. This pLess commonly used when compared to rest-stress, stress-first CTP is best suited for patients with intermediate to high pretest risk known intermediate/indeterminate stenosis, or prior revascularization where the assessment of ischemia in a particular vascular territory is favored over coronary anatomy Fig. b. When pz-axis coverage up to 105 mm and, thus, can image the cardiac volume without the need for table shuttling [Static imaging techniques, with or without stress acquisitions, are limited to single snapshots in time and do not provide comprehensive blood flow analysis. Historically, limitations in scanner technology made static CTP the only viable method. However, the latest generation 256- and 320-row detector platforms allow for imaging of the entire cardiac volume with a stationary table and a single gantry rotation. Additionally, second-generation dual-source CT (DSCT) can cover this same volume utilizing a table shuttle method. The third-generation DSCT has increased huttling , 55, 71.huttling . MBF calhuttling , 73. In huttling , 60. Thehuttling , 73. DynDECT was first introduced in 2008 and has undergone several advancements and innovations in the last decade that have significantly increased its diagnostic utility , 75. DECPost-processing of CTP datasets relies on the visual assessment of the ischemic myocardial segments in comparison to normally perfused myocardium Fig. . MultiplRadiation dose, as mentioned above, continues to be a limitation to widespread implementation of CTP protocols. Newer generation scanners and the possibility of single acquisition CCTA and stress CTP hold promise for lowering radiation dose to levels more comparable to SPECT. Imaging artifacts, specifically beam hardening from the descending thoracic aorta, can affect interpretation of the inferolateral wall segments by mimicking a perfusion defect in that territory. Utilization of beta-blockers and nitrates, as is often required for acquisition of CCTA data, reduces the sensitivity of CTP scans by masking smaller, typically single-vessel, perfusion defects as shown in the SPECT literature , 99. FinOver the last two decades, advancement in CMR with LGE has revolutionized the assessment of myocardial fibrosis secondary to infarction, infiltration, or inflammation. The ability of CMR to assess these various tissue states is based on the pathologic effects on the tissues resulting in changes in tissue density and differential uptake of gadolinium. Iodinated contrast has similar kinetics and distribution to gadolinium allowing for the potential of DECT to detect infarction similar to CMR . As mentCCT can serve as an important adjunctive modality to TTE in patients with known or suspected cardiomyopathies, primarily in patients with claustrophobia, implantable cardiac devices, and poor TTE windows. In the setting of newly diagnosed heart failure with a reduced ejection fraction, CCTA is well validated to exclude significant CAD in patients with low to intermediate pretest risk of CAD. In patients with reduced EF less than 35%, CCTA for the evaluation of CAD has a reported sensitivity of 98% and specificity of 97% . While a18F-fluorodeoxyglucose (FDG). FDG PET imaging, taking advantage of differences in glucose metabolism between normal myocytes and diseased myocytes, has the ability to detect hibernating myocardium in viability testing and myocyte inflammation as seen in acute cardiac sarcoidosis [PET when combined with CT has emerged as a powerful diagnostic modality, both in ischemic heart disease as well as various inflammatory and infiltrative disease processes. PET imaging is commonly undertaken to assess the metabolic activity of tissue utilizing the glucose analog coidosis . Imagingcoidosis .While the utility of DE images has been discussed as it relates to infarct detection in ischemic heart disease, iodine mapping with single- or dual-energy CT can also be employed in the assessment of other cardiomyopathies where epicardial and midmyocardial scar patterns are currently observed on CMR exclusively. CCT-based estimation of extracellular volume (ECV) by CCT may become a useful diagnostic and prognostic marker of myocardial remodeling similar to that observed with T1 mapping by CMR –113. StrCCT in the form of CTP, particularly when combined with CCTA, is a powerful tool in the assessment of ischemic heart disease and, with newer generation scanner platforms, presents the potential for full functional and anatomic assessment with a single contrast injection and low radiation dose dataset acquisition. CCT is a useful adjunct to both TTE and CMR in the evaluation of ventricular volumes and systolic function, particularly in patients with implantable cardiac devices or severe claustrophobia. Newer applications of CCT, namely dynamic CTP and DECT, are promising diagnostic tools offering the possibility of more quantitative assessment of ischemia than offered by static perfusion imaging. Finally, given its superior spatial resolution and volumetric acquisition, CCT has an important role in the diagnosis of other nonischemic causes of cardiomyopathies most notably LVNC, ARVC, and HCM.