Myocardial contusion can be a life-threatening condition in patients who sustained blunt thoracic trauma. The diagnostic approach remains a subject of debate. The aim of this study was to determine the sensitivity and specificity of echocardiography, electrocardiography, troponins T and I (TnT and TnI), and creatine kinase muscle/brain (CK-MB) for identifying patients with a myocardial contusion following blunt thoracic trauma.Sensitivity and specificity were first determined in a 10-year retrospective cohort study and second by a systematic literature review with meta-analysis.Of the 117 patients in the retrospective study, 44 (38%) were considered positive for myocardial contusion. Chest X-ray, chest CT scan, electrocardiograph, and echocardiography had poor sensitivity (< 15%) but good specificity (≥ 90%). Sensitivity to cardiac biomarkers measured at presentation ranged from 59% for TnT to 77% for hs-TnT, specificity ranged from 63% for CK-MB to 100% for TnT. The systematic literature review yielded 28 studies, with 14.5% out of 7242 patients reported as positive for myocardial contusion. The pooled sensitivity of electrocardiography, troponin I, and CK-MB was between 62 and 71%, versus only 45% for echocardiography and 38% for troponin T. The pooled specificity ranged from 63% for CK-MB to 85% for troponin T and 88% for echocardiography.The best diagnostic approach for myocardial contusion is a combination of electrocardiography and measurement of cardiac biomarkers. If abnormalities are found, telemonitoring is necessary for the early detection of life-threatening arrhythmias. Chest X-ray and CT scan may show other thoracic injuries but provide no information on myocardial contusion.The online version of this article (10.1007/s00068-020-01305-4) contains supplementary material, which is available to authorized users. Myocardial contusion describes a condition of bruising or  hemorrhaging of the heart muscle caused by blunt thoracic trauma. In patients who have sustained blunt thoracic trauma, the prevalence of myocardial contusion ranges from 0 to 76%, depending on the diagnostic criteria used –10.The bruising is generally caused by a decelerating force on the anterior side of the thorax –14. FirsThe absence of a clear definition and the fact that there is no accepted gold standard in complementary tests makes diagnosing myocardial contusion difficult. The diagnostic approach of myocardial contusion as well as its clinical course remain subject to debate, because of heterogeneity in clinical presentation and the unpredictable natural course , 15–20. Myocardial contusion is often accompanied by significant extracardiac injuries which may have hemodynamic effects, thereby hampering the possible diagnosis of a myocardial contusion. Patients with hemodynamic changes but without a clear bleeding or cardiac tamponade are very suspect for myocardial contusion , 14, 24.Although several diagnostic tests are available, none of them have shown sufficient diagnostic accuracy for diagnosing myocardial contusion , 28–32. However, no consensus exists in the optimal diagnostic workup for patients with a possible myocardial contusion. To develop a diagnostic protocol, more insight into the diagnostic properties of the tests available is needed. Therefore, the aim of this study was to determine sensitivity and specificity of echocardiography, electrocardiography, troponins T and I, and CK-MB to identify patients with a myocardial contusion following blunt thoracic trauma. This was done both in a retrospective cohort and by systematic literature review with a meta-analysis.Patients presented to a level I trauma center with a suspected myocardial contusion after blunt force thoracic trauma between January 1, 2007, and June 30, 2017, were considered eligible for this single-center retrospective cohort study. The study was exempted by the local Medical Research Ethics Committee.Potentially eligible patients  were identified using two strategies. Searching electronic hospital discharge letters and correspondence to General Practitioners that mentioned myocardial contusion (or any synonym possible) resulted in a list of admitted and non-admitted patients. Patients who were admitted to the hospital were also identified from the National Trauma Registry by searching for patients with a registered Abbreviated Injury Score (AIS) for any myocardial injury. The AIS-1998 codes were 441099.1, 441002.1, 441004.1, 441006.4, 441008.3, 441010.3, 441012.5, 441014.6, 441016.6, 441018.6, 441200.5, and 441300.5. The AIS-2005 codes were 441089.9, 441099.1, 441002.1, 441004.1, 441006.4, 114008.3, 441010.3, 441012.5, 441013.5, 441014.6, 441016.6, 441018.6, 441200.5, 441300.5, and 440400.5. Two authors (DJTVS and EAD) identified the eligible patients from these lists. All patients in whom a myocardial contusion was considered were included. Consideration of a myocardial contusion had to be clear from the physician’s notes in the patient’s medical files and could due to results of anamnesis or diagnostic tests. Exclusion criteria were (1) no suspicion of myocardial contusion; (2) trauma mechanism other than blunt trauma; (3) confirmed (non)-ST elevation myocardial infarction [(non-)STEMI]; (4) no diagnostic or outcome data available.Patient characteristics, injury characteristics, results from patient history, physical examination, diagnostic tests  were collected from medical records. During hospital stay, relevant findings during clinical and telemetric observation, electrocardiography, transthoracic echocardiography, levels of cardiac biomarkers, cardiac adverse events, mortality, and surgical interventions were also collected from the patient’s medical files. Patient characteristics included gender, age at trauma, comorbidities, use of medication that either mask or cause cardiac arrhythmia, and renal function . Thoracic injury characteristics are rib fractures, hemothorax, pneumothorax, cardiac valve defects, sternum fracture, flail chest, pulmonary contusion, and aorta dissection. Details on patient history and physical examination were complaints of chest pain, palpitations, dyspnea, fainting, cardiac murmurs, cardiac rubbing, oxygen saturation, heart rate, systolic and diastolic blood pressure, and Glasgow Coma Score.Diagnostic tests were checked for signs of abnormalities. For chest CT and X-ray, suspicion of the presence of pericardial effusion was collected from the radiology report. Electrocardiograms (ECGs) were reviewed by a cardiologist (EAD) for signs of ST elevation, ST depression, T-wave inversion, arrhythmia, or intraventricular conduction abnormalities. Transthoracic echocardiography was reviewed (by EAD) for signs of regional wall motion abnormalities, pericardial effusion, or mechanical abnormalities. No transesophageal echocardiography was performed.Thresholds for increased levels of cardiac biomarkers were 30 ng/L for normal-sensitive troponin T  and 14 ng/L for high-sensitive troponin T . Cut-off values for creatine kinase MB (CK-MB) were 7.6 µg/L for men and 4.7 µg/L for women.Relevant findings during clinical observation with or without telemetry, levels of cardiac biomarkers, electrocardiography, echocardiography, and cardiac adverse events that might suggest myocardial contusion were registered. Relevant cardiac adverse events were arrhythmias , hypotension, and cardiogenic shock requiring inotropic support. In addition, data on relevant surgical interventions, its outcome, and mortality were collected.Based upon all available data and final judgement of the treating physician as mentioned in the patient’s medical files, patients were categorized as having had a myocardial contusion or not. Diagnostic tests were also categorized as positive or negative for myocardial contusion. No single test could serve as a gold standard for the diagnosis. Signs indicative of myocardial contusion are (1) elevated cardiac biomarkers; (2) new valve defects, regional wall motion abnormalities, pericardial effusion, or other anatomical defects seen on echocardiography; (3) intraventricular conduction abnormalities, atrial fibrillation, premature ventricular complexes, and supraventricular tachycardia seen on electrocardiography.https://www.medcalc.org/calc/diagnostic_test.php). Patients with versus patients without myocardial contusion were compared. Normality of continuous data was tested with the Shapiro–Wilk test, which showed that all were non-normally distributed. Continuous data are shown as median with quartiles and categorical data are shown as numbers with percentage. Statistical significance between the two groups was assessed using a Mann–Whitney U test for continuous data and a Chi-square test or Fisher exact test for categorical data. A two-sided p value < 0.05 was used as threshold of statistical significance. For each diagnostic test, myocardial contusion prevalence, sensitivity, and specificity were calculated and are reported as percentage with 95% confidence.Data were analyzed using the Statistical Package for the Social Sciences version 24.0  and MedCalc  independently. Any disagreement was resolved by consensus. First, titles and abstracts of all manuscript were reviewed for eligibility. Next, the full text of all remaining studies was screened for eligibility. For all included studies, the reference list was reviewed for identifying studies that were missed during the selection process.Risk of bias assessment and applicability concerns for each study was carried out using the QUADAS-2 tool. For each study, the following data were extracted: author, publication year, study design, study population size, mean age, number of patients diagnosed with myocardial contusion, and the number of patients with ischemic heart disease or acute myocardial infarction. For echocardiography, electrocardiography, and cardiac biomarkers, the number of true and false positives and negatives were extracted for each study. In addition, the reference test and cut-off values for cardiac biomarkers used for identifying the myocardial contusion group were recorded.Sensitivity and specificity were calculated using Review Manager . Subsequent meta-analysis was done using Meta-analysis of Diagnostic and Screening Tests (Meta-DiSc) . Sensitin = 372) and the trauma registry  years  than in those who were not diagnosed with a myocardial contusion . The four most common injuries were a sternum fracture, rib fracture(s), pneumothorax, and pulmonary contusion. Rib fractures occurred more often in patients with a myocardial contusion than patients without . The same was true for pulmonary contusion . Rates of all other thoracic injuries were similar in both groups.The rate of non-cardiac thoracic injuries was higher in patients with a myocardial contusion , a lower median mean arterial pressure (MAP) , and a lower median Glasgow Coma Scale .Details of patient history could be found for 80% of patients; 39 (41%) patients had chest pain, 4 (4%) had dyspnea, 1 (1%) had palpitations, and none had cardiac rubbing Table . None ofChest CT scan, electrocardiography, and transthoracic echocardiography made at hospital presentation were indicative of myocardial contusion in only one patient who showed retrosternal hematoma Table . Five pap < 0.001). Abnormalities suggestive of myocardial contusion at the electrocardiography made during admission were shown only in one patient with a myocardial contusion. Levels of cardiac biomarkers remained higher at follow-up in patients with a myocardial contusion than in patients without, as was the case in the initial screening.Overall, 111 patients with a suspected myocardial contusion were admitted for observation. Telemonitoring was done in 91% of patients with a myocardial contusion versus 59% of patients without myocardial contusion  than controls . The most common adverse event was arrhythmia, which was seen in 13 patients with a myocardial contusion . Eight of these 13 patients with a myocardial contusion had atrial fibrillation or flutter. Rib fractures occurred more often in patients who developed an adverse event: 12 out of 18 (67%) patients with an adverse event had fractured ribs, versus 49 out of 99 (49%) in patients who remained free of adverse events. Seven patients died, four patients with a myocardial contusion and three patients without myocardial contusion. Of the patients with myocardial contusion, one patient died of cardiogenic shock due to a known mitral valve dysfunction; in two other patients, treatment was stopped due to infaust neurological prognosis after trauma. In the fourth patient, no cause of death was noted and autopsy was not performed. One patient without myocardial contusion died of pulmonary embolism, the other two due to infaust neurological prognosis after trauma.Thirty-three cardiac adverse events had developed in 18 patients Table . PatientThe search strategy resulted in 3443 records, of which 1665 remained after removing duplicates , conduct or interpretation of the index test (n = 10), the reference standard (n = 10), and patient flow and timing , index test (n = 14), and reference standard (n = 18).The risk of bias was judged as low for most studies in the domains of patient selection . This may reveal left or right ventricular systolic dysfunction, pericardial effusion with suspected tamponade, ventricular septal defect, or possible trauma-induced valvular abnormalities .Results from the electrocardiography (and echocardiography) and cardiac biomarkers support the subsequent diagnostic necessities and monitoring. Patients with abnormalities on the electrocardiography (or echocardiography) that are not explained by (non-)STEMI or by cardiac diseases that were already present pre-trauma, should be considered suspect for myocardial contusion. If cardiac biomarkers are also elevated, measurement of these markers should be repeated after 3 h. In addition, telemonitoring is required for early knowledge of possible development of life-threatening arrhythmias or other complications. The patient data in this study confirm the relevance of this as 13 patients with myocardial contusion developed some form or arrhythmia over time. Cardiac monitoring should last at least 24–48 h because life-threatening ventricular arrhythmias, cardiac failure due to valve damage, cardiac tamponade due to a wall rupture, or acute coronary syndrome due to coronary artery dissection may develop within this period , 71, 72.If cardiac biomarkers are not elevated in patients with electrocardiography abnormalities, the biomarkers should be measured again after 3 h, as they may become positive. If the cardiac biomarkers remain negative and no other clinical suspicion of myocardial contusion has emerged, the diagnosis can be rejected. Emerging clinical suspicion or elevated markers at follow-up, on the other hand, supports the presence of myocardial contusion. Telemonitoring is indicated in those patients.If both cardiac biomarkers are not elevated and the electrocardiography shows no abnormalities, myocardial contusion is unlikely. It was shown previously that patients with a normal electrocardiogram in conjunction with normal levels of troponin can be safely discharged home , 67, 68.The current study has several limitations. The most obvious limitations are the retrospective nature of the cohort study and the lack of a gold standard in both the cohort study and all studies in the literature review. Personal opinion of the treatment team may have led to false positive of false negative results for myocardial contusion. These differences in diagnostic criteria used, variation in biomarker cut off values, as well as differences in study population may have contributed to the heterogeneity across studies in the meta-analysis. This may have resulted in differences in sensitivity and specificity of the different diagnostic tests across the published as well as our cohort study. This heterogeneity also warrants careful interpretation of the pooled sensitivity and specificity.Data from the current study support that initial diagnostic workup in patients who presented to a hospital after blunt thoracic trauma should consist of electrocardiography and measurement of cardiac biomarkers. If the electrocardiography shows abnormalities indicative of myocardial contusion and/or cardiac biomarkers are elevated at presentation or become elevated within the subsequent 3 h, echocardiography and telemonitoring are indicated. If electrocardiography is normal and cardiac biomarkers remain negative, clinical observation may suffice. Further prospective studies are needed to refine the proposed diagnostic scheme.Supplementary file1 (DOCX 158 kb)Supplementary file2 (DOCX 45 kb)Below is the link to the electronic supplementary material.


Background: Chromogranin B (CgB) is increased in heart failure and proportionate to disease severity. We investigated whether circulating CgB level is associated with left ventricular (LV) functional recovery potential after successful recanalization of chronic total occlusion (CTO).Methods: Serum levels of CgB were assayed in 53 patients with stable angina with LV functional recovery [an absolute increase in LV ejection fraction (EF) of ≥5%] and 53 age- and sex-matched non-recovery controls after successful recanalization of CTO during 12-month follow-up.Results: We found that CgB level was significantly lower in the recovery group than in the non-recovery group , and that it was inversely correlated with changes in LVEF . Receiver operating characteristic (ROC) analysis showed that the area under the curve of CgB for predicting LVEF improvement was 0.76 (95% CI 0.664–0.856), and that the optimal cutoff value was 972.5 pg/ml. In multivariate analyses, after adjusting for confounding factors, high CgB level remained an independent determinant of impaired LV functional recovery after CTO recanalization. LV functional improvement appeared to be more responsive to CgB in patients with poor than with good coronary collaterals.Conclusions: Elevated circulating CgB level confers an increased risk of impaired LV functional recovery after successful recanalization of CTO in patients with stable coronary artery disease. Chronic total occlusion (CTO) occurs in 18–31% of patients with significant coronary artery disease undergoing routine coronary angiography –7. There2+-dependent signaling (Chromogranin B (CgB), also known as secretogranin I, is a tyrosine-sulfated protein widely expressed in secretory granules of endocrine, neuroendocrine cells, and cardiomyocytes –14. In cignaling . In animignaling . Remarkan = 27), history of coronary artery bypass grafting (n = 19), renal failure requiring hemodialysis (n = 5), and malignant tumor (n = 5), as these conditions could influence collateral formation. Forty-six patients were further excluded because of unavailability of blood samples. Thus, 363 patients were enrolled and underwent baseline echocardiography. Due to the study purpose of LV functional recovery, we excluded 137 patients with baseline LV ejection fraction (LVEF) ≥55%. Additional 32 patients were excluded because of unsuccessful CTO recanalization. The cohort was followed up for around 12 months and underwent repeat echocardiographic examination. There were 5 patients who died from any cause, and 32 got lost to follow-up. Afterward, 157 patients were kept, and 53 pairs of age- and sex-matched patients with or without LV functional recovery were enrolled in the final analysis  of at least one major epicardial coronary artery between September 2017 and May 2019 were screened from the database of Shanghai Rui Jin Hospital PCI Outcomes Program. The duration of coronary artery occlusion was estimated from the date of occurrence of myocardial infarction in the area supplied by the occluded vessel, from abrupt worsening of existing angina pectoris, or from information obtained from a previous angiogram. For study purpose, 56 patients were excluded because of recent PCI within last 3 months , and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were determined with standard laboratory techniques. Estimated glomerular filtration rate (eGFR) was computed using the Chronic Kidney Disease Epidemiology Collaboration equation. Serum CgB was assayed using an enzyme-linked immunosorbent assay (ELISA) kit .Blood samples were obtained on the day of angiography from all the patients after overnight fasting. To avoid a diurnal variation in CgB concentration and dramatic fasting interval effects, all blood samples were obtained at 8:00 am. Serum levels of creatinine, lipid profiles, glucose, glycosylated hemoglobin Avia connections of the epicardial surface or intraventricular septum) was visually estimated using the Rentrop grading system  with a 1.9–3.8-mHz phased-array transducer by a single sonographer credentialed in cardiac ultrasound. Two-dimensional echocardiography and Doppler flow imaging were recorded from standard parasternal and apical transducer positions with a frame rate of 60–100 frames/s. All data were stored digitally, and an offline analysis was performed  by two independent experienced cardiologists at the end of the study blinded to the study time point.LVEDD + IVST + LVPWT)3 − LVEDD3]+0.6, where LVEDD is LV end-diastolic diameter, IVST is interventricular septal thickness, and LVPWT is LV posterior wall thickness. LV mass was indexed by BSA. LV function recovery was defined as an absolute increase in LVEF of ≥5% 1 year after recanalization of CTO lesions.Left ventricular (LV) end diastolic and end systolic volumes, and LVEF were measured using the modified Simpson's biplane technique in a cardiac cycle not preceded or followed by a premature complex, according to the recommendations of the American Society of Echocardiography and the European Association of Cardiovascular Imaging for cardiac chamber quantification by echocardiography in adults . To facit-test. For non-normally distributed continuous variables, differences were analyzed by Mann-Whitney U-test. Differences in categorical variables were analyzed by χ2-test. The correlations between CgB, NT-proBNP, LVEF and their changes were analyzed by Spearman's correlation test. The diagnostic value of CgB was calculated by constructing a receiver-operating characteristic (ROC) curve, and the optimal cutoff threshold was determined by Youden's index. Three models were constructed in the multivariate analysis. In model I, all conventional risk factors and significant predictors were enrolled followed by backward stepwise elimination. Afterward, CgB level (model II), collateral conditions and their interaction term with CgB were further included (model III). Restricted cubic spline analysis was performed to evaluate the relationship between CgB levels and LV functional recovery under different collateral conditions after multivariate adjustment. Net reclassification improvements (NRIs) and integrated discrimination improvements (IDIs) were analyzed to assess the improvement in clinical utility of the prediction model by considering CgB. All the statistical analyses were performed using the R statistical package version 4.0.3 . A 2-tailed p < 0.05 was considered statistically significant.Continuous variables are presented as median (interquartile range) or mean ± standard deviation (SD), and categorical data are summarized as frequencies (percentages). The normal distribution of continuous variables was evaluated by Shapiro-Wilk test. For normally distributed variables, differences in serum CgB were compared by Student's Patients with or without LV functional recovery after CTO recanalization did not differ with respect to history of hypertension, diabetes, previous myocardial infarction, smoking habits, blood pressure, renal function, and medical treatments. The distribution of CTO lesions and collateral conditions were similar between the 2 groups. Interestingly, patients with LV functional recovery had lower fasting glucose but higher total and LDL cholesterol levels than non-recovery subjects. Serum levels of NT-proBNP were also comparable between the 2 groups .P = 0.062; ESVI: P = 0.409) and LVEF (P = 0.647). During follow-up, mean increase in LVEF was 9.91 ± 3.52% in the recovery vs. 0.19 ± 2.99% in the non-recovery group. Pronounced LV reverse remodeling was observed in the recovery rather than non-recovery patients   .P < 0.001, P = 0.001) during the 1-year follow-up but not to baseline LVEF  or NT-proBNP levels . ROC curve analysis showed that the area under the curve (AUC) of CgB for predicting LV functional recovery after CTO-PCI was 0.76 (95% CI 0.664–0.856), and that the optimal cutoff threshold was 972.5 pg/ml, which corresponded to a diagnostic sensitivity of 88.7% and specificity of 62.3%  between CgB level and collateral conditions (model III). Patients with poor collaterals appeared to be more responsive to CgB levels with regard to LV functional recovery than those with good collaterals . Multivariate analysis  revealedlaterals .P < 0.001), and IDI was 23.38% .The inclusion of CgB led to better prediction accuracy. In the non-recovery patients, 29.1% was correctly reclassified to lower probability categories, and 10.9% was reclassified to higher categories. In patients with LV functional recovery, 21.4% was correctly reclassified to higher probability categories, and none was reclassified to lower probability categories. The categorical NRI was 39.61% , Shanghai Municipal Commission of Health and Family Planning (Grant Nos: 2018YQ17 and 20194Y0042), Shanghai Science and Technology Commission Natural Fund Project (17ZR1417200), Shanghai High School Fellowship Program for Research & Translation (Grant No: RC0030103), Ruijin Youth Training Program (Grant No: 2019QNPY01033), and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20181801).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Background: Myocardial ischemia occurs in pediatrics, as a result of both congenital and acquired heart diseases, and can lead to further adverse cardiac events if untreated. The aim of this work is to assess the feasibility of fully automated, high resolution, quantitative stress myocardial perfusion cardiac magnetic resonance (CMR) in a cohort of pediatric patients and to evaluate its agreement with the coronary anatomical status of the patients.Methods: Fourteen pediatric patients, with 16 scans, who underwent dual-bolus stress perfusion CMR were retrospectively analyzed. All patients also had anatomical coronary assessment with either CMR, CT, or X-ray angiography. The perfusion CMR images were automatically processed and quantified using an analysis pipeline previously developed in adults.Results: Automated perfusion quantification was successful in 15/16 cases. The coronary perfusion territories supplied by vessels affected by a medium/large aneurysm or stenosis (according to the AHA guidelines), induced by Kawasaki disease, an anomalous origin, or interarterial course had significantly reduced myocardial blood flow (MBF) (median (interquartile range), 1.26  ml/min/g) as compared to territories supplied by unaffected coronaries  and territories supplied by vessels with a small aneurysm .Conclusion: Automatic CMR-derived MBF quantification is feasible in pediatric patients, and the technology could be potentially used for objective non-invasive assessment of ischemia in children with congenital and acquired heart diseases. Cardiac magnetic resonance (CMR) has been gaining in importance as a technique for the assessment of a wide variety of congenital and acquired heart diseases in children. It provides both functional and anatomical assessment, with good spatial resolution, without exposing patients to ionizing radiation. This is of particular importance as children are more likely to develop radiation-induced cancer than adults  and theyStress perfusion CMR has been repeatedly shown to possess both good sensitivity and good specificity for the non-invasive assessment of myocardial ischemia –19. AlthThe quantification of myocardial blood flow (MBF) from stress perfusion CMR is possible and has been shown to be of high diagnostic and prognostic value , 27. RecPediatric cardiac MRI perfusion datasets from a single institution , acquired between 2010 and 2018 were retrospectively analyzed. This study was performed under the ethical approval of the local ethics committee (Ethics No. RJ109/N112). Patients who underwent dual-bolus perfusion protocol  were incCoronary artery aneurysms are assessed according to the American Heart Association scientific statement 2017 , with a All patients had anatomic coronary artery changes (stenosis or dilatation) and either symptoms of angina or electrocardiographic evidence of ischemic changes at rest or during exercise.k-t sensitivity encoding (k-t SENSE) acceleration with 11 training profiles was used to achieve a representative spatial resolution of 1.25 × 1.25 × 10 mm3. Stress images were acquired during adenosine-induced hyperemia (140 μg/kg/min). 0.075 mmol/kg of bodyweight gadolinium (Gd) extracellular contrast agent  was injected at 4 mL/s followed by a 20-mL saline flush for each perfusion acquisition. Each bolus of gadobutrol was preceded by a diluted pre-bolus with 10% of the dose to allow quantification of perfusion, according to published methods (Perfusion images were acquired in three left ventricular (LV) short-axis slices  at mid-expiration when possible. Due to the young age of the patients and the potential side effect of adenosine infusion, younger patients required general anesthesia during CMR study, with volatile anesthetics (isoflurane and sevoflurane). Heart rate lowering medications, such as remifentanil, were not used. Where the heart rate did not permit the acquisition of three slices in every heartbeat, the basal and mid-cavity slices were acquired. Imaging was performed with a saturation-recovery acquisition sequence on either a 1.5T  or 3T system . The typical imaging parameters were at 1.5T with a 12-channel cardiac phased array receiver coil: balanced gradient echo readout, repetition time/echo time 3.0 ms/1.5 ms, flip angle 50°, saturation-recovery delay 100 ms and at 3.0T with a 32-channel coil: gradient echo readout, repetition time/echo time 2.5 ms/0.9 ms, flip angle 20°, saturation-recovery delay 120 ms. Five-fold  methods .The perfusion images were corrected for respiratory motion  and procThe descriptive statistics are presented as mean ± standard deviation (SD) or median [inter-quartile range (IQR)] for non-normally distributed variables. The distributions of quantitative MBF values are compared using the non-parametric Mann-Whitney U test. The significance level α = 0.05 was used to determine statistical significance. This analysis was performed using SciPy .A total of 42 patients underwent stress perfusion cardiovascular magnetic resonance scans between 2010 and 2018. Fourteen patients (with 16 scans) underwent scans being performed with a dual-bolus acquisition and thus were included in the study. Fourteen scans were done at 1.5 T and 2 scans were done at 3 T. Two patients underwent a repeat stress perfusion scan for follow up. 12/16 scans were performed under general anesthesia. The patient's demographic and baseline data are given in p < 0.001). The MBF estimate in patients with Kawasaki disease but with no significant coronary involvement was 2.57  ml/min/g. This was not significantly different to the MBF [2.52  ml/min/g] in coronary territories with a small aneurysm p = 0.525. There was a reduction in MBF in coronary territories perfused by vessels with a medium/large aneurysm, a stenosis, an anomalous origin, or an interarterial course to 1.26  ml/min/g. This was significantly lower as compared to normal patients (p < 0.001) and territories with small aneurysm (p = 0.002) with the distributions of the per-coronary perfusion territory MBF values visualized in The median pixel-wise MBF estimate across all subjects was 2.34  ml/min/g. The median pixel-wise MBF in patients with visual ischemia was 1.84  ml/min/g, which was significantly lower than that in patients with no visual perfusion defect 2.48  ml/min/g  and positron emission tomography (PET) but both subject the patient to ionizing radiation and are limited in spatial resolution as compared to CMR. Furthermore, adenosine stress perfusion CMR is considered to have a good safety profile amongst pediatrics , making The limitation of stress perfusion CMR is that it requires expertise to acquire and interpret the images , 38. ThiThe results of our retrospective study show that fully automated quantification of first pass stress perfusion CMR is feasible in pediatrics and that the CMR measurements of stress MBF well match the corresponding anatomical images of the patients. For the example patient shown in The technical difficulties to be dealt with in order to facilitate the widespread clinical adoption in pediatric patients include the need for higher temporal and spatial resolutions to cope with the higher heart rates and smaller heart size as compared to adults, patient motion and the inability to breath-hold. However, solutions to these challenges are becoming available. Accelerated MR image acquisitions and in particular, spatiotemporal data under-sampling approaches combined with multi-element coil spatial encoding have shown that it is feasible to acquire high resolution images at very high heart rates while reducing dark rim artifacts . FurtherThe major limitation of this study is that it is a retrospective study with a small sample size. However, in light of this proof of feasibility, a larger study is now warranted. The myocardial blood flow values were not compared to a gold standard test or a control group, however, this is a frequently encountered limitation in studies involving pediatrics due to the ethical considerations of this vulnerable age group and the need to avoid unnecessary procedures. Furthermore, coronary anatomical assessment was primarily done via CMRA and not CT or X-ray angiography, despite the latter being the gold standard procedure. However, this is justifiable in the light of the incorporation of CMR as an acceptable modality for coronary assessment in many published guidelines, as well as the reduced radiation exposure.Voxel-wise quantification of MBF in pediatric patients is feasible and correlates with the anatomical status of corresponding coronary perfusion vascular territory. This makes use of highly accelerated pulse sequences to achieve sufficient spatial and temporal resolution. Advanced motion compensation and automated image processing methods provide a fully objective interpretation of perfusion, circumventing the need for time-consuming processing and experienced operators. While further studies are need, quantitative perfusion CMR represents a promising tool for the non-invasive management of children with heart diseases.The raw data supporting the conclusions of this article will be made available upon request by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Evelina London Children Local Ethics Committee (Ethics No. RJ109/N112). Written informed consent to participate in this study was provided by the participant's legal guardian/next of kin.CS, HH, PD, and AC designed the study, collected and analyzed the data, and drafted the initial manuscript. GG and TH collected and analyzed the data. RR, JL, and KP designed the study, reviewed, and edited the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


P = 0.01) was found. This is a negative association to RV E/A (P = 0.004), and RV end diastolic diameter (RVED) longitudinal (P = 0.01). A positive association between BSA and RVED middle (P = 0.001), as well between BSA and RAA (P = 0.05) was found, along with a negative association with RV E/A (P = 0.002). A positive association between intensity of training and RV end systolic area (RVESA) (P = 0.03), RV end diastolic volume indexed (RVEDVI) (P = 0.01), RV end systolic volume indexed (RVESVI) (P = 0.01) was found, along with a negative association with ejection fraction (EF %) (P = 0.01). Endurance athletes demonstrated an association between RV remodelling and age, BSA and intensity of training.Long-term sports training leads to myocardial adaptations, with remodelling of the heart chambers. However, while myocardial adaptations of the left heart are well described, remodelling of the right heart and its impact on the development of arrhythmias is still debated. To conduct a systematic review on right ventricle (RV) and right atrium (RA) structural and functional changes in athletes who participate in long-term endurance training. Systematic review. A systematic literature search was conducted. All the articles reporting right heart echocardiographic (ECHO) and cardiac magnetic resonance (CMR) parameters evaluated in endurance athletes and sedentary subjects were considered eligible. A multivariate analysis was conducted to investigate whether age, sex, body surface area (BSA), intensity of training are associated with RV ECHO, CMR parameters and RA ECHO parameters. A positive association between age and right atrium area (RAA) ( Heart remodelling is different following endurance training and resistance training11.“Athlete’s heart” refers to remodelling of the whole cardiac muscles induced by the high workload of sports training12. A clear classification is not possible as the overall size of cardiomyocytes increases under both remodelling patterns. In general, the thickness of the LV wall prevails in resistance training as a consequence of chronic volume overload; LV dilatation is a prominent characteristic in endurance-trained heart, mainly determined by chronic systolic pressure overload13.In endurance training, the left ventricle (LV) undergoes eccentric hypertrophy, while resistance training promotes concentric hypertrophy14. Also, there seems to be an association between RV hypertrophy and Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)17, one of the major causes of cardiac death in young athletes19. Therefore, it would be interesting to define exercise-induced RV adaptation, and its impact on the onset of arrhythmias16. Endurance training causes greater morphological and functional RV changes than any other type of exercise, but the role of variables such as age, sex and BSA has not been established20. Endurance training increases the hemodynamic needs with a consequent chronic pressure elevation in the cardiac chambers21. As a result, long-term exercise leads to permanent RV structural and functional modifications, with large interindividual variability22. It is important to distinguish between acute and chronic adaptations, and to consider exercise loading and intensity23, which induce different functional and clinical consequences23. Immediately after an intense exercise, the serum level of troponin and B-type natriuretic peptide increases24. A process of micro injuring and healing occurs, mirroring what take place in skeletal muscles, which, eventually, leads to myocardial adaptation22.However, exercise-induced changes of the right ventricle (RV) are still debatedThis study investigates the structural and functional changes of the right ventricle (RV) and right atrium (RA) in athletes who participate in long-term endurance training, and defines whether the RV ECHO and CMR reference values for the general population are appropriate for endurance athletes.25. We followed the PICO protocol for the preliminary search:P (Problem): right heart in endurance athletes;I (Intervention): long-term endurance sport training;C (Comparator): right heart in sedentary individuals;O (Outcomes): morphological and functional ECHO and CMR parameters.The present systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recomendationsright ventricle, right atrium, right heart, heart chambers, endurance, athletes, echocardiography, cardiac magnetic resonance, sport, players, remodelling, adaptation, training, work out. Only studies published from 2000 up to May 2021 were accessed. Resulting titles and abstracts of interests were screened by the two authors independently. The full text of the articles of interest were examined. Disagreements about the eligibility of a study were resolved were solved by a third author (FM).Two authors  independently performed the literature search in May 2021. The following databases were used for the search: Medline, Scopus and Cochrane. To conduct a comprehensive systematic literature search, we used both controlled vocabulary and free text terms. For our research, the following MESH terms were used: 26. Data from national registries were excluded, as well as reviews, letters, expert opinions, case reports, editorials, animal, computational and cadaveric studies. As the aim was to investigate the remodelling of the right heart in endurance athletes, only study which investigated athletes who regularly played sports listed on the Mitchel Category class C27 were examined. Only studies reporting right heart ECHO and/or CMR parameters of endurance athletes and a sedentary group as controls were eligible. To evaluate chronic adaptations, only CMR or an ECHO evaluation performed at rest were considered. The exclusions criteria were represented by all the variables which could alter the physiological parameters: the presence of diseases, a family history of pulmonary or cardiac diseases, chronic use of drugs.According to the authors’ language capabilities, articles in English, Italian, French, German, Portuguese and Spanish were considered. Studies with level of evidence I to III, according to the Oxford Centre for Evidence-Based Medicine (OCEBM), were consideredgeneralities displayed author and publication year and general characteristics of our population: number of athletes, number of sedentary individuals, sex, age, body mass index (BMI), body surface area (BSA), heart rate (HR), training hours and years of training.ECHO data to assess the morphological and functional parameters of the right heart: basal, middle, longitudinal right ventricle end diastolic diameter (RVED) and their values BSA indexed, right ventricle end diastolic area (RVEDA), end systolic area (RVESA) and their values BSA indexed, right ventricle wall thickness (RVWT), right ventricle E/A (RV E/A), fractional area change (FAC %), ejection fraction (EF %) tricuspid annular plane excursion (TAPSE), right ventricle outflow tract  and their values BSA indexed, right atrial area (RAA), right atrial volume (RAV) and their value BSA indexed.CMR data to assess the morphological and functional parameters of the right heart: right ventricle end diastolic volume (RVEDV), right ventricle end systolic volume (RVESV), right ventricle stroke volume (RVSV), mass and their value BSA indexed and ejection fraction (EF %).Data were extracted by two different authors . Data from the following end-points were collected:The primary outcome of interest was to investigate the association between right heart remodelling and age, sex, BSA and intensity of training. The second outcome of interest was to compare the mean values of endurance athletes morphological and functional parameters. To underline the different adaptation of RV in male and female among CMR studies, five studies were selected, in which parameters referred to male athletes, male sedentary, female athletes, female sedentary were reported separately. In these studies, the difference of the means between male athletes-male sedentary subjects and female athletes-female sedentary subjects were compared.28. The NOS evaluates three parameters, namely selection, comparability and exposure. The parameter selection domain includes 4 items useful to check definition and representativeness of cases and controls; the comparability domain includes 1 item to compare cases and controls based on the study design or analysis; the exposure domain includes 3 items to evaluate methods adopted in the study to ascertain exposure for cases and controls28. The maximum score for each study is nine points, and a study with lesser than five points is considered at high risk of bias. The NOS has been described as a reliable tool to assess the quality of case control studies and cohort studies29.The same two reviewers who extracted data  assessed the risk of bias of the included studies using the Newcastle Ottawa Scale (NOS)r |< 0.3, 0.3 <| r |< 0.5, and | r |> 0.5 were considered to have small, medium, and strong correlation, respectively. The test of overall significance was performed through the χ2 test, with values of P < 0.05 considered statistically significant. For continuous variable, mean and standard deviation was evaluated. The T test was performed, with P < 0.05 considered statistically significant.For the multivariate analyses, the STATA/MP 16.1  was used, with a multiple linear model regression diagnostic. For pairwise correlation, the Pearson Product-Moment Correlation Coefficient (r) was used. The final effect was evaluated according to the Cauchy–Schwarz inequality: + 1 (positive linear correlation) and − 1 (negative linear correlation). Values of 0.1 <| The search resulted in 2280 articles. After removing duplicates (N = 696), a total of 1584 articles were screened. A further 1166 articles were excluded because of: the type of the study (N = 508), the absence of sedentary controls (N = 193), sports not listed on the Mitchel Category class C (N = 131), language limitations (N = 7), evaluation after an acute stress (N = 118), presence of diseases (N = 209). Another 364 studies were excluded because they did not match the topic of interest or did not report quantitative data on outcome of interest. Finally, 54 articles were included in the analysis: 32 articles reporting ECHO parameters, 20 reporting CMR parameters, 2 reporting both. The flowchart of the literature search is shown in Fig. The NOS scale evidenced an overall high quality of the included studies. Studies eligibility criteria and sports category were well described, as were the selection criteria of control groups. The intensity of training was seldom reported. Demographic characteristics were often exhaustively described. The procedure to assess outcomes was overall clearly described. The description of ECHO and CMR results was also comprehensive. A NOS scale score > 8 was achieved by all the included studies.In ECHO studies, data from 2102 athletes and 1311 sedentary practice were collected. The mean age of athletes and sedentary was 26.6 ± 8.6 and 26.6 ± 7.6, respectively. The BSA was 1.86 ± 0.2 and 1.82 ± 0.15, respectively. The BMI of athletes was 24.8 ± 2.01 and BMI of sedentary was 22.89 ± 1.32. HR was 57.3 ± 7.06 and 69.6 ± 5.26, respectively. In CMR studies, data from 1257 athletes and 909 sedentary subjects were collected. The mean age of athletes and sedentary was 31.5 ± 9.8 and 31.9 ± 8.8, respectively. The BSA was 1.89 ± 0.19 and 1.87 ± 0.15, respectively. The BMI of athletes was 22.4 ± 0.5, and that of sedentary participants was 24.4 ± 1.1. HR was 57.3 ± 7.06 and 63.4 ± 6.9, respectively. Population demographics is shown in Table P = 0.009, r = − 0.63). Age showed also a statistically significant negative and strong association to RVED longitudinal in athletes . Age showed evidence of statistically significant strong positive association with an increased rate of progression to RAA both in the athletes and sedentary controls . BSA showed statistically significant strong positive association with an increased rate of progression to RVED middle in athletes , while in sedentary subject there was evidence of statistically significant moderate positive association with an increased rate of progression . Also, BSA showed statistically significant strong positive association with an increased rate of progression to RAA both in athletes and sedentary controls . Notably, BSA showed statistically significant strong negative association to ratio RV E/A in athletes . With regard to ECHO data, intensity of training showed evidence of statistically significant strong positive association with an increased rate of progression to RVESA . Considering CMR data, the intensity of training presented statistically significant positive and, respectively, strong moderate association to RVEDVI and RVESVI . Moreover, evidence of a statistically significant moderate negative association was found between the intensity of training and EF % . The multivariate analysis is shown in Table Age showed evidence of statistically significant moderate negative association to RV E/A in athletes (P = 0.001), as shown in Table A statistically significant difference was observed between RVEDVI means difference values in male and RVEDVI means difference values in female . Data are reported in Table In athletes, EF % showed evidence of a statistically significant strong negative association to RVEDV and RVESV  and in females (athletes versus sedentary) were analysed. There are no differences in the kinetics of trend of adaptation between males and females, with the exception of RVEDV, and all the other parameters showed a similar trend of adaptation both in female and male endurance athletes. Age and increased BSA in athletes are linked to a decrease in diastolic function with a reduction in RV E/A. The intensity of exercise training is associated with heart morphological remodelling. The studies show that 6–8 h/w are sufficient to induce remodelling evident on ECHO and CMR33. Another goal of this systematic review was to discuss whether the normal RV reference values fitted the RV characteristics in endurance athletes. Athletes involved in endurance sport have different ECHO parameters from those of the general population20. Comparing the studies’ results with the reference values, the mean values of all considered parameters in endurance athletes are higher than those of the general population indicated by the American Society of Echocardiography and the European Association of Cardiovascular Imaging34. Furthermore, there is a difference between the reference mean values adopted for CMR parameters and the mean values in endurance athletes35. This is in accordance with an earlier systematic review, which underlines how endurance sport induces the most significant modification in the right heart, with eccentric hypertrophy12. Such structural changes could lead to incorrectly diagnose ARVC. The ARVC is a group of cardiomyopathies with a similar phenotype and tendency to ventricular arrhythmias. Mutations encoding desmosomal genes are associated to ARVC. In some individuals the phenotypical expression can be triggered by endurance exercise training15. The mean values of RVEDVI are 132.25 ± 9.63 mL/m2 and 109.5 ± 9.35 mL/m2 respectively for males and females, and they are both over the limit of the major criteria for diagnosis of ARVC 30. The value of 30.24 ± 1.11 mm for RVOT1 is below the limit of major criteria (≥ 32 mm) but it is included in the minor criteria limit (≥ 29 to ≤ 32 mm), while the BSA indexed value (20.18 ± 4 mm/m2) is just above the major criteria limit (≥ 19 mm/m2). The value of 31.83 ± 2.34 mm for RVOT2 is above the limit of the minor criteria (> 32 mm), and the RVOT2/BSA (22.3 ± 3.15 mm/m2) is beyond the limit of the major criteria (> 21 mm/m2). Functional parameters (FAC % and EF %) are not over the limit for diagnosis of ARVC 28. A low value of RV E/A is a sign of diastolic disfunction36. As highlighted in previous studies, age affects diastolic function, with proliferation of extracellular matrix and crosslinking of collagen fibres4. The present study shows that a negative association is evident among athletes, but not among sedentary subjects. Some chronic cardiac microinjuries can emphasise the physiological mechanisms of extracellular matrix rearrangement and fibrotic alteration that normally occur with aging. This leads to a decrease in right heart wall compliance with a reduction in diastolic function. Low values in EF % are related to ventricular chamber dilatation, as shown in Table 22.Although EF% decreases, this is not sufficient to justify a systolic disfunction or any other pathological condition, and it should be regarded as a physiological adaptation to the increase in EDV and ESV. To make a correct diagnosis of ARVC, it is important to examine the family history, and to fulfil the other Task Force criteria30. Pathology should be suspected when ECHO shows akinesia, dyskinesia, or an aneurysm, because they are not features of athlete’s heart37. Indeed, the remodelling induced by endurance sport could resemble a cardiomyopathy, but the real impact on future morbidity is still unknown. However, if a subject has a latent ARVC, sport-induced adaptation could deteriorate this condition16.Endurance athletes demonstrated a statistically significant association between RV remodelling and age, BSA and intensity of training. 2-D ECHO is the easiest way to assess morphological and functional parameters of the right heart, and CMR became fundamental to evaluate the RV morphologyCardiac remodelling is evident in both sexes, but the lack of studies investigating separately ECHO parameters in male and female athletes does not allow to thoroughly assess similarity and differences. Also, atrial adaptations should be considered, but there are still few studies which analyse atrial chamber remodelling in athletes. A positive association was shown between RAA and age, and between RAA and BSA, but the data available on RA were fewer than data on RV: other studies should be conducted to assess the impact of RA remodelling in endurance athletes. Similarly, years of training were not taken into account because of the lack of relevant data, and further investigations could be conducted to ascertain how many years of training induce permanent RV modifications. The impact of systolic and diastolic disfunction should be analysed considering a longer follow-up period to estimate the incidence of cardiovascular diseases in endurance athletes. Future studies should overcome these limitations to offer a more complete overview.Endurance athletes exhibit an association between RV remodelling and age, BSA and intensity of training. In particular, RV E/A is an age-related functional parameter, and it should be carefully evaluated because it is a marker of diastolic dysfunction. The systolic function of the RV is decreased in endurance athletes. This is a normal adaptation to exercise, induced by structural changes, and it is within the normal limits. RV ECHO and CMR values in endurance athletes are slightly different from the reference values established in the general population. This could lead to an incorrect diagnosis of ARVC.Supplementary Information 1.Supplementary Information 2.


Background and purpose — Quantitative T2 mapping MRI of cartilage has proven value for the assessment of early osteoarthritis changes in research. We evaluated knee cartilage T2 relaxation times in a clinical population with knee complaints and its association with patients and disease characteristics and clinical symptoms.Patients and methods — In this cross-sectional study, T2 mapping knee scans of 109 patients with knee pain who were referred for an MRI by an orthopedic surgeon were collected. T2 relaxation times were calculated in 6 femoral and tibial regions of interest of full-thickness tibiofemoral cartilage. Its associations with age, sex, BMI, duration of complaints, disease onset (acute/chronic), and clinical symptoms were assessed with multivariate regression analysis. Subgroups were created of patients with abnormalities expected to cause predominantly medial or lateral tibiofemoral cartilage changes.Results — T2 relaxation times increased statistically significantly with higher age and BMI. In patients with expected medial cartilage damage, the medial femoral T2 values were significantly higher than the lateral; in patients with expected lateral cartilage damage the lateral tibial T2 values were significantly higher. A traumatic onset of knee complaints was associated with an acute elevation. No significant association was found with clinical symptoms.Interpretation — Our study demonstrates age, BMI, and type of injury-dependent T2 relaxation times and emphasizes the importance of acknowledging these variations when performing T2 mapping in a clinical population. Knee osteoarthritis (OA) is currently mainly diagnosed on clinical presentation  from Stanford University Medical Center were eligible for the study.The patients were scanned on a 3.0 Tesla (T) MRI scanner  with a flexible 16-channel receive-only coil . The patient’s knee was fixed with a leg holder in slight flexion to position the coil and reduce motion artifacts. In addition to a routine clinical knee MR protocol used by the radiologist to assess structural changes in the knee, a 3D fast spin echo T2 mapping sequence was added to the protocol during the trial period. This sequence with variable refocusing flip angle schedules uses T2 magnetization preparation followed by pseudo steady-state 3D FSE acquisition , disease characteristics , and clinical symptoms were retrospectively collected through the electronic patient record. Diagnosis was based on the surgical report (when available), clinical report, and MRI report. The surgical report was considered the reference in case of discrepancies between the reports. The duration of complaints, defined as the period between the onset of knee pain and the date of the MRI, was divided into acute (< 1 month), subacute (1–6 months), and chronic (> 6 months). The onset of disease was specified as traumatic versus non-traumatic. To assess clinical symptoms, the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire was recorded for patients on their first visit to the Outpatient Clinic . Associations between T2 relaxation times and patient characteristics, disease characteristics, and clinical symptoms were tested using linear regression models. T2 relaxation times were used as dependent variable and patient characteristics, disease characteristics, and clinical symptoms as independent variables. We performed both univariate and multivariate analyses. Subgroups were created of patients with abnormalities expected to cause predominantly isolated medial  or lateral tibiofemoral cartilage changes  . Informed consent was obtained from all participants. This research was not supported by grants from any funding agency in the public, commercial, or not-for-profit sectors. The dataset that is necessary to replicate main findings can be obtained from the authors upon reasonable request. GEG and EHGO receive research support from GE Healthcare. The study was performed during the visiting professorship of EHGO at Stanford University Medical Center, which was partially funded by the Dutch Arthritis Foundation.146 patients met the inclusion criteria of whom 109 were eligible for further analyses . Main reData on BMI was missing for 3 patients. In the multivariate analysis with age, sex, and BMI as independent variables, age showed a statistically significant association with T2 relaxation times in all medial ROIs and the lateral weight-bearing tibial ROI, as well as the total tibiofemoral cartilage . IncreasWe identified 35 patients with abnormalities that are the likely cause of medial cartilage damage. The medial femoral ROIs showed statistically significantly higher T2 relaxation times compared with the lateral femoral ROIs . 21 patiA trend towards decreased cartilage T2 values with an increase in duration of complaints was observed . HoweverMean KOOS values and standard deviations per subscale are displayed in In this study, we assessed the association of T2 relaxation times of the tibiofemoral knee cartilage with patient and disease characteristics and clinical symptoms in an unselected clinical population of 109 patients. A positive statistically significant association was observed between T2 relaxation times and age and BMI, while sex did not have an effect on T2 relaxation times. Age seemed to have an overall effect on T2 values as increasing T2 values with increasing age were seen in most ROIs. Increasing T2 relaxation times with aging and higher BMI have previously been described in patients over 45 years old (Joseph et al. Differences in T2 values between medial and lateral compartments were found in patients with unicompartmental abnormalities. Previous studies with strict inclusion criteria already showed increasing T2 relaxation time in the medial knee compartment in patients with meniscal tears and in the lateral knee compartment in patients with anterior cruciate ligament injuries (Friedrich et al. Duration of complaints could potentially lead to transient variation of T2 relaxation times within patients as evidence is provided that the integrity of the cartilage collagen network is compromised soon after joint injury (Lohmander et al. As far as we know, no imaging modality has shown a good correlation with clinical symptoms of knee injury and osteoarthritis in an unselected routine clinical population. In our study, significant associations were found between T2 values and two domains of the KOOS questionnaire in the univariate analysis. However, this finding was not sustained when corrected for age, sex, and BMI, with age being the predominant covariate. When looking at the item-specific analysis, we found only “any difficulty with descending stairs” to be correlated with T2 relaxation times after correction. Although a large set of symptoms was tested, and based on repeated testing coincidental findings are possible, previous studies also reported difficulties with climbing stairs to be a sensitive and prodromal symptom in osteoarthritis (Case et al. Our study has several limitations. By using a clinical orthopedic population, we included patients with a wide range in age, BMI, diagnoses, and clinical symptoms. The combination of this heterogeneity and limited sample size could explain the absence of clear associations between T2 values and disease characteristics and clinical symptoms in our study. A second limitation is that we had a valid KOOS questionnaire available for only half of the patients. It was common practice at the Orthopedic Outpatient Department to ask patients to fill in the questionnaire. Unfortunately, this was not strictly controlled. We are aware that previous studies have shown T2 differences between superficial and deep cartilage layers (Mosher et al. To date, the application of T2 mapping is primarily in clinical research with patient groups based on well-defined inclusion criteria. In contrast to the success of T2 mapping in research trials like the OAI, the poor associations of T2 mapping with patient and disease characteristics observed in our study illustrate the difficulties of implementing such a quantitative MR technique in a routine clinical population. In conclusion, our results emphasize the importance of acknowledging patient and disease characteristics when performing T2 mapping in a clinical population.JV, SJvL, GEG, JLD, SMABZ, MR, and EHGO contributed to the design of the work. JV, SJvL, JLD, GEG, and EHGO contributed to the acquisition of the data. JV, SJvL, GEG, JLD, SMABZ, MR, and EHGO contributed to the analysis and interpretation of the data. All authors contributed to drafting the work or revising the content critically and all authors have approved the final version. JV and EHGO have full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.Acta thanks Carl Johan Tiderius and other anonymous reviewers for help with peer review of this study.


Cardiomyopathy is the most common presenting feature of Barth syndrome, often presenting in infancy with severe heart failure and cardiac dysfunction. Historically, affected infants commonly died early after presentation, sometimes before a diagnosis of Barth syndrome was made. With increases in awareness of Barth syndrome and in the care of infants with severe heart failure, survival of children with Barth syndrome and severe heart failure has improved. We describe our experience caring for five unrelated boys with Barth syndrome who presented with severe cardiomyopathy and heart failure prior to age 2 who have had marked improvement with long‐term response to medical heart failure therapy. Early recognition and appropriate medical therapy can lead to sustained resolution of symptomatic heart failure and improvement in the cardiomyopathy phenotype of Barth syndrome.1TAFAZZIN on chromosome Xq28.12 result in abnormal cardiolipin metabolism and mitochondrial dysfunction.http://www.barthsyndrome.org/).Barth syndrome is a rare multisystem disorder characterized by cardiomyopathy, skeletal muscle weakness, growth delay, and neutropenia.Cardiomyopathy is the most common presenting feature.2A summary of select clinical, echocardiographic, and ECG features is shown in Table 2.1P1 had a history of hypotonia and undiagnosed developmental delay and presented at age 21 months with acute onset left sided weakness in the setting of a presumed respiratory viral infection. While his facial droop resolved prior to arrival in the emergency room, initial examination was significant for a II/VI blowing systolic murmur at the apex, a gallop, and hepatomegaly. Brain MRI confirmed a right middle cerebral artery stroke in the setting of embolic occlusion of the right internal carotid artery as well as a left parietal stroke. Chest x‐ray demonstrated cardiomegaly with increased pulmonary vascularity. As shown in Figure TAFAZZIN (c.222C > A), consistent with Barth syndrome, as well as 15q11.2q13 and 15q13.3 microduplications.P1 was admitted to the Cardiac Intensive Care Unit (CICU) where he was intubated and started on milrinone and epinephrine to support cardiac output. He was treated with enoxaparin for his thromboembolic stroke. Workup of his DCM revealed 3‐methylglutaconic aciduria and he was ultimately confirmed to have a missense mutation in exon 2 of P1 was discharged after a 20‐day inpatient stay. His medical heart failure management at discharge included captopril three times a day (0.9 mg/kg/dose), carvedilol twice a day , and furosemide twice a day (1 mg/kg/dose). While he has remained well compensated on medical oral heart failure therapies since initial hospital discharge, his echocardiogram initially began to show subtle improvement in LV dilation and dysfunction by 4 months of therapy, with progressive improvements in LV size and systolic function noted at 7 and 9 months after starting treatment. By 12 months on oral medical heart failure therapies, his LV size was only mildly dilated  with a normal EF 55% and by 16 months on therapy (age 38 months) both LV size and EF were normal. He remains on an angiotensin converting enzyme‐inhibitor (ACE‐inhibitor), now enalapril, at last evaluation at age 7 years, having weaned off both furosemide and carvedilol with normal LV size  that had not previously been reported.P2 presented to the emergency department at almost 6 months of age for persistently increased work of breathing, wheezing, cough, and cardiomegaly on chest x‐ray. Past medical history was significant for vesicoureteral reflux, asymmetric crying facies, polydactyly, sacral dimple, and poor weight gain. Initial examination revealed no murmur or gallop, but hepatomegaly was appreciated. As shown in Figure P2 was discharged after a 14‐day hospital stay on oral heart failure therapy of captopril three times a day (0.5 mg/kg/dose) plus furosemide every morning (1 mg/kg/dose). After readmission 6 weeks later for worsening heart failure symptoms in the setting of a febrile illness, digoxin twice daily (4.7 mcg/kg/dose) was added. He subsequently was readmitted 3.5 months after starting heart failure therapy for gastrostomy button placement due to poor weight gain. Although echocardiogram at 8 months after diagnosis continued to show severe LV dilation and dysfunction with subtle improvement when normalized for body surface area , by 10.5 months on heart failure therapy there was clear improvement in LV size  and systolic function . At this point furosemide was weaned and three times daily captopril transitioned to twice‐daily enalapril for convenience in dosing. Further improvement  was observed on echocardiogram at 14 months on therapy (age 21 months), though most echocardiograms since have shown mild LV dilation (LVIDd and LVIDs z‐scores 2–3.5) with mildly decreased systolic function (EF 45–50%). Carvedilol was added at age 20 months.P2 was last seen at age 10 years and had no heart failure symptoms on twice daily enalapril (0.26 mg/kg/dose), carvedilol (0.26 mg/kg/dose), and digoxin (2.6 mcg/kg/dose). His most recent echocardiogram showed a mildly dilated and globular LV left ventricle .P3 presented at 2 months of age for an episode of lassitude and pallor and was found to have cardiomegaly on chest x‐ray. He was initially admitted to the NICU for a sepsis evaluation; however, was transferred to the CICU after echocardiography showed severe LV dilation , captopril three times a day (1.1 mg/kg/dose), digoxin twice a day (3.8 mcg/kg/dose), and furosemide twice daily (1.3 mg/kg/dose). His systolic LV function by echocardiography had improved on discharge (EF 18%), with stable LV dilation. Two months after discharge, his LV was less dilated  and systolic function mildly improved (SF 23%). On his subsequent echocardiogram at 6 months on heart failure therapy (at 8 months of age), his LV systolic function was normal , with normal LV size . While he remains on chronic ACE‐inhibitor therapy, furosemide was stopped at 10 months and digoxin 13 months after diagnosis. He was last seen in clinic at 11 years of age. As shown in Figure 2.4TAFAZZIN (c.347G > A). As shown in Figure P4 presented on day of life two after becoming tachypneic and hypothermic in the newborn nursery. A chest x‐ray demonstrated cardiomegaly and he was acidotic with lactate of 16 mmol/L. He was resuscitated with intravenous fluids, intubated, and started on intravenous epinephrine and milrinone, and transferred to the CICU. There was a strong family history of infantile death of five maternal great uncles between 1 week and 5 months of birth from heart failure. This raised a clinical suspicion for Barth syndrome that was later confirmed by genetic testing showing a missense pathogenic variant in During close outpatient follow‐up, his oral heart failure regimen was augmented and his echocardiogram showed improvement in LV size at 9 months of age  with continued decreased systolic function . He continued to gain weight on oral heart failure therapies  with similar echocardiogram findings until 26 months of age when the LV size and systolic function were both essentially normal . He was last seen in cardiology clinic at 13 years of age with long‐standing symptoms of easy fatigability, thought to be secondary to peripheral muscle involvement from Barth syndrome, and episodic emesis that has not been responsive to multiple gastroenterology evaluations and medication trials or transition from ACE‐inhibitor to angiotensin receptor blocker. He has no hepatomegaly and BNP levels are consistently normal (last 43 pg/ml). His most recent echocardiogram Figure  showed m2.5TAFAZZIN allele (IVS1‐17C > T) in the intron 1 coding region. Clinically he was suspected of having Barth syndrome, and multiple investigations for other etiologies were negative until whole exome sequencing at age 11 years revealed a TAFAZZIN pathogenic variant (c.778‐24_778‐7delinsA).P5 presented at 4.5 months of age with 2–3 months of decreased oral intake and failure to thrive. He was referred for cardiology evaluation due to tachypnea and cardiomegaly on chest x‐ray and on examination had a laterally displaced apical impulse with a subtle gallop but no hepatomegaly. Family history was positive for a maternal uncle with infantile onset cardiomyopathy and heart failure who died at age 4 years. Echocardiogram demonstrated moderate to severe LV dilation  with severely decreased function . He was admitted for further evaluation into the etiology of his cardiomyopathy and started on medical heart failure management with captopril and furosemide. Metabolic evaluation was significant for 3‐methylglutaconic aciduria and genetic evaluation initially demonstrated a nonpathogenic During outpatient follow‐up his echocardiogram remained unchanged at 6, 9, and 12 months on heart failure therapy with ACE‐inhibitor , carvedilol, and furosemide; however, after 18 months on heart failure treatment (22 months of age) his echocardiogram was much improved . His echocardiogram was stable over the next 5 years until at age 7 years, it began to show atrial dilation and elevated pulmonary artery pressure; features consistent with diastolic dysfunction/restrictive physiology. Over the next 6 years on the same heart failure medications (uptitrated for growth), his echocardiogram showed progressive biatrial dilation, mitral, and tricuspid insufficiency, and pulmonary hypertension with stable, mild LV dilation (LVIDd z score 2–3), and normal to mildly decreased systolic function (EF 47–55%). Around age 12, he began to manifest dyspnea on exertion and cardiac catheterization confirmed elevated filling pressures with elevated, but reactive pulmonary vascular resistance (PVR 5 indexed Wood units). Serial ambulatory ECG monitoring from diagnosis performed approximately annually showed no significant ectopy. In the absence of effective medical therapies for restrictive cardiomyopathy with associated pulmonary hypertension, he was referred for heart transplantation, which he received at age 14 years. He remains well at 1 year after transplantation with resolution of pulmonary hypertension  who had decreased cardiac function and medically treated heart failure upon outpatient transfer of care to our center who shortly thereafter required ventricular assist device support and subsequent heart transplantation. While outcomes after heart transplantation for individuals with Barth syndrome were recently shown to be the same as for matched peers with DCM without Barth syndrome,In this series, we present five children with Barth syndrome who presented under age 2 with symptomatic heart failure who had extended responses to medical heart failure therapy with resolution of heart failure symptoms and near normalization to normalization of LV size and systolic function. This is important because the prevailing description of outcomes for infants with severe cardiomyopathy and Barth syndrome in the medical literature is commonly of death, need for mechanical circulatory support, and/or heart transplantation.Normalization of LV size and function has been reported to occur in approximately 20% of children with DCM, with younger age and less severe LV dilation at diagnosis reported as predictors in a Pediatric Cardiomyopathy Registry (PCMR) study.The decision to continue indefinite medical HF therapy in these boys deserves brief mention. While all had resolution of their clinical HF symptoms, not all achieved normalization of all echocardiographic parameters and some later showed decline in SF/EF and/or increase in LV dilation. Furthermore, the underlying substrate for HF  remains and individuals with Barth syndrome have been described to have improvement followed by worsening over time. An improved understanding of why cardiac function varies over time is vitally important to optimally caring for individuals with Barth syndrome. In lieu of this, we have elected to maintain all of our patients with Barth syndrome who have not required transplantation on indefinite HF medications. Further, there is randomized clinical trial evidence in adults with nonischemic DCM who had resolution of HF and LV reverse remodeling on medical HF therapy that shows frequent relapse of HF and LV dilation/dysfunction following withdrawal of therapy.It is important to acknowledge that the improvements in these five individuals were achieved through a combination of awareness of the diagnosis of Barth syndrome, provision of multidisciplinary care , and receipt of appropriate acute and chronic heart failure therapies. Transplant‐free survival for all children with DCM has improved over the last two decades, likely due to improved medical treatment of heart failure.In summary, we report on five children with Barth syndrome who presented symptomatic heart failure and LV dilation and systolic dysfunction in early life who achieved long‐term improvements of heart failure symptoms and near normalization to normalization of LV size and systolic function with timely diagnosis and medical heart failure management.Dr Feingold serves voluntarily on the Barth Syndrome Foundation Scientific and Medical Advisory Board. He also serves as a consultant for Stealth Biotherapeutics. Dr Yester has no relevant disclosures.Dr Yester performed chart review, assisted in conceptualization of the work, drafted the manuscript, figures, and table, and critically revised the manuscript. Dr Feingold conceptualized the work, guided data abstraction, and led critical revision of the manuscript, figures, and table.This research was performed by approval of the University of Pittsburgh Human Research Protection Office (PRO# 19050115) via waiver of informed consent.Dr. Feingold serves as guarantor for the article, accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. This work was supported by the Thomas and Jennifer McCrady Heart Failure and Transplantation Research Fund at UPMC Children's Hospital of Pittsburgh.


For systemic diseases like rheumatoid arthritis, systemic lupus erythematosus (SLE), systemic sclerosis, systemic vasculitis, myopathies, and mixed connective tissue diseases, cardiac disease is a major contributing factor for morbidity and mortality. The cardiovascular manifestations are the result of various pathophysiological components, which complicate management. Furthermore, the signs and symptoms can be subtle and missed due to the complex nature of the underlying condition. As a result, various imaging approaches play an imperative role in diagnosis and prognosis. The evolving role of these modalities could lead to risk stratification and improved therapies in the future. In conclusion, our review article will highlight the role of cardiac imaging in the evaluation of cardiac involvement for systemic diseases. Systemic diseases encompass a broad spectrum of diverse pathologies with many overlapping clinical features like rheumatoid arthritis, systemic lupus erythematosus (SLE), systemic sclerosis, systemic vasculitis, myopathies, and mixed connective tissue diseases. Despite their heterogeneous nature, these disorders are linked by their cardiovascular involvement, which can affect diagnostic pathways . CardiacThe manifestations of CVD in systemic diseases can be attributed to a variety of pathophysiologic phenomena such as vascular inflammation, micro or macro ischemia, and myocardial fibrosis . With thRole of imaging in systemic diseaseThe complex nature of CVD in systemic diseases compels the need for proper diagnostic modalities for adequately assessing the pathophysiological processes. Echocardiography, nuclear imaging, and x-ray coronary angiography have been long-established pillars in cardiovascular imaging Table  1]. The. The1]. A Brief Overview Of Diagnostic Modalities In Systemic DiseasesEchocardiography is the first-line diagnostic modality used in a variety of conditions . It can In nuclear imaging, single-photon emission computed tomography (SPECT) and PET are frequently used in clinical cardiology. Nevertheless, these modalities have relatively low specificity for the identification of coronary artery disease (CAD). Similar to echocardiography, they cannot characterize tissue properties in systemic diseases . There aMulti-slice CT can assess the calcification and extent of atherosclerosis in the coronary artery. It can evaluate for myocardial scarring. Very few studies have explored the possibilities of tissue characterization with CT. Some disadvantages include the high utilization of iodinated contrast agents and varying levels of expertise that have been limiting its growth in CVD of systemic diseases .CMR is a non-invasive modality that utilizes photons for the production of various images. CMR enables excellent spatial resolution and tissue characterization. It is reproducible and provides valuable information regarding myocardial inflammation. A number of studies have explored the role of CMR in various systemic diseases Table . FurtherLimitations of CMRThere are still a number of limitations to CMR. Though late gadolinium enhancement (LGE) can be a useful approach, it cannot detect diffuse fibrosis . LGE is Rheumatoid arthritisRheumatoid arthritis (RA) is a chronic inflammatory disorder involving a number of joints ,12-13, gImaging Modalities in Rheumatoid ArthritisEchocardiography is the fundamental cornerstone of cardiovascular examination and it is the most widely used noninvasive imaging technique . EchocarMyocardial perfusion imaging with SPECT enables the assessment of CAD noninvasively. It has been reported that myocardial perfusion imaging with PET has higher diagnostic accuracy than SPECT . In nuclMulti-slice CT with iodinated contrast agents enables visualization of the coronary lumen. It also identifies significant coronary artery stenosis and permits characterization of the atherosclerotic plaque. CT has shown very high accuracy in the early diagnosis of CAD . The AgaCT coronary angiography also permits the evaluation of the coronary arteries non-invasively. Compared to invasive coronary angiography, the sensitivity of both approaches is quite similar . A normaCMR can non-invasively measure ejection fraction and volumes and provide three-dimensional images . CMR hasCoronary magnetic resonance angiography (MRA) requires a lot of expertise and is gaining traction. It has been used in the evaluation of coronary arteries in RA and provided information about coronary lesions . FurtherComparison of CMR with Other Modalities in Rheumatoid ArthritisWhile echocardiography is the commonly used modality for assessing ventricular function, CMR has accurate measurements with good correlation . EvaluatSystemic lupus erythematosus SLE is an autoimmune disorder with widespread organ involvement having a variable course . It is tImaging Modalities in SLEEchocardiography should be performed in all SLE patients irrespective of symptoms . Left veNuclear studies are frequently used to evaluate the level of myocardial ischemia in SLE patients prior to and following interventional procedures . PerfusiCT can evaluate calcification in the coronary artery to assess the extent of atherosclerotic progression . Few stuCMR is the imaging approach of choice for evaluation of the pathophysiologic process of heart disease in SLE and does not have concerns for radiation . It can Cardiac catheterization is an interventional approach that provides valuable diagnostic information in CAD. The information provided by cardiac catheterization can guide therapeutic intervention. For evaluating pulmonary artery pressures, cardiac catheterization can be hailed as the gold standard . LimitedComparison of CMR with Other Modalities in SLE Echocardiography is the most frequently used diagnostic modality for evaluating cardiovascular disease in SLE 36). As stated earlier, it is operator-dependent and can have poor acoustic windows in some patients. In patients with conflicting results during routine testing, CMR can provide additional information [. As statCT has been able to detect myocardial fibrosis in hypertrophic cardiomyopathy patients with contrast enhancement . StudiesSystemic sclerosisSystemic sclerosis (SSc) is characterized by abnormal collagen accumulation and fibrosis resulting in dysfunction of vascular organs. Cardiac involvement can occur secondary to fibrosis and PAH. Microvascular dysfunction and fibrosis can lead to compromised systolic and diastolic function .Imaging Modalities in Systemic Sclerosis Early subclinical lesions can be seen with echocardiography, nuclear, and cardiac CMR studies . These aComparison of CMR with Other Modalities in Systemic SclerosisThe diagnosis and detection of myocardial fibrosis are not clearly defined in SSc . Most noDobutamine stress echocardiography can identify wall motion abnormalities and provide information on myocardial blood flow . SimilarSarcoidosisSarcoidosis is a granulomatous condition linked with damage to the myocardium -70. TherRole of Imaging Modalities in SarcoidosisThe absence of a gold standard test and low sensitivity of the invasive endomyocardial biopsy has led to the diagnosis of sarcoidosis being made on clinical grounds . An echoOver many years, CMR and PET have been able to document cardiac involvement comparable to autopsy reports . The HeaCMR is frequently utilized in the assessment of cardiac sarcoidosis and can detect myocardial damage and fibrosis . Once ceSystemic vasculitidesSystemic vasculitides consist of a spectrum of disorders characterized by inflammation and necrosis of the inner vessel wall of blood vessels . They arRole of Imaging in Systemic VasculitidesThough endomyocardial biopsy may be the gold standard in diagnosis, it is not always ideal due to the haphazard distribution of inflammation . CMR enaMixed connective tissue diseases and myopathiesThere are limited studies evaluating the potential of imaging for cardiac involvement in mixed connective tissue diseases. CMR can detect inflammation and fibrosis, which can possibly initiate treatment in mixed connective tissue diseases -89. In cThe spectrum of cardiovascular features in systemic diseases is the result of various interactions among various pathological factors, which require multi-center studies and clinical trials to fully understand the multi-faceted nature of cardiac involvement in these complex heterogeneous conditions. The application of various imaging modalities can have a major diagnostic and prognostic impact on patient management. Even though there is no single imaging technique that has the high sensitivity, specificity, and reproducibility to detect inflammation, ischemia, scar, vasculitis, and microvascular dysfunction without limitations, CMR is assuring and superior among all the imaging techniques available.


Cardiomyopathy and associated heart failure have uncommon etiologies, which when diagnosed reduce patients’ morbidity and mortality. One such entity is left ventricular non-compaction cardiomyopathy (LVNC). Still, a relatively uncommon entity, the manifestation of LVNC may range from asymptomatic to left ventricular dysfunction, congestive heart failure, ventricular tachycardia, sudden cardiac death, and thromboembolic complications. If not pursued as a possible etiology of non-ischemic cardiomyopathy, patients may have significantly increased morbidity prior to eventual diagnosis. Patients are often predisposed to ventricular arrhythmias requiring implantable cardiac defibrillator placement. Additionally, due to the depth of trabeculations, there is an associated thromboembolic risk requiring therapeutic anticoagulation. We present the case of a 41-year-old man with progressively worsening heart failure due to undiagnosed LVNC and the associated deleterious manifestations and outcomes. Left ventricular non-compaction cardiomyopathy (LVNC) is the most recent cardiomyopathy classified as a distinct entity by the American Heart Association and remains a heterogeneous and complex entity. Still a relatively uncommon entity, LVNC may go undetected with deleterious outcomes for the affected individual. Establishing the diagnosis of LVNC requires a high index of clinical suspicion when a patient presents with non-ischemic cardiomyopathy. The diagnosis of LVNC carries with it an increased risk of ventricular arrhythmias, systemic embolism, progressive heart failure and even sudden cardiac death . LVNC poWe present a 41-year-old man with a past medical history of chronic New York Heart Association (NYHA) Class II-III heart failure with reduced ejection fraction (HFrEF), non-ischemic cardiomyopathy, obstructive sleep apnea, chronic kidney disease and gastroesophageal reflux disease. His home medications were Entresto 24/26mg orally twice daily, carvedilol 3.125mg orally twice daily, pantoprazole 40mg orally twice daily and Maalox 30cc orally every six hours as needed for indigestion. There was no known family history of heart disease, sudden or premature death. He is a former smoker and does use alcohol or illicit drugs, and had serum ethanol less than 10 and urine drug screen negative. He was initially diagnosed with cardiomyopathy of uncertain etiology, HFrEF and he was told that his ejection fraction (EF) was 20%-25% (no records available), two years prior at another facility. There was no ischemic workup at that time and he was discharged on carvedilol, furosemide, lisinopril and metoprolol tartrate (unknown dosages of medications). Subsequently, he had his first presentation to our institution with exertional dyspnea in the context of decompensated HFrEF. At that time, he underwent cardiac catheterization which revealed no significant coronary artery disease Figures -1E. Ther 2 99% on ambient air. His normal dry weight was approximately 330lbs (149.7kg) and his weight at the time of presentation was 350lbs (158.8kg). Physical examination revealed reduced breath sounds bilaterally with significant rales, along with bilateral lower extremity pitting edema. The remainder of his systems examination was within normal limits. EKG demonstrated normal sinus rhythm at 73 beats per minute, ventricular trigeminy, no pathologic Q-waves, left axis deviation, possible left atrial enlargement, poor precordial R-wave progression and nonspecific T-wave abnormality , regular heart rate of 76 beats per minute with increased pulse volume, respiratory rate 24 breaths per minute, temperature 98.2F and SpOThe patient presented with clinical features consistent with decompensated heart failure. As such, he was diuresed successfully to euvolemia with intravenous furosemide. He experienced persistent sinus bradycardia with a nadir of 40 beats per minute likely of multifactorial origin - deoxygenation from congestive heart failure , superimAt two months post dual-chamber cardiac defibrillator system placement and GDMT, the patient was asymptomatic and euvolemic with adequate perfusion. However, there was persistent hypotension limiting the use of afterload reducing agents and this will be followed closely in the outpatient setting. On discharge, we recommended that his first-degree relatives, his children, be screened. Additionally, his outpatient cardiologist will arrange for potential genetic testing of the patient.LVNC is a heterogeneous and complex entity. While the American Heart Association includes it among genetic cardiomyopathies, the European Society of Cardiology treats it as an unclassified cardiomyopathy. It may present in a sporadic or familial form, isolated or associated with other heart diseases, affecting only the left ventricle or both and can sometimes appear as a mixed phenotype in patients with other cardiomyopathies. Different forms of clinical presentation are also associated with its different morphological manifestations, and non-compaction of the left ventricle may be triggered by other physiological or pathological processes . Non-comClassically, LVNC has been referred to as the triad of heart failure, arrhythmias and embolic episodes. However, its presentation is very heterogeneous and covers a broad spectrum, from asymptomatic patients diagnosed by familial or another screening context to advanced heart failure and sudden death . With reThe outpatient cardiac MRI was done shortly prior to presentation demonstrated an NC to C ratio of >2.3 in end-diastole, estimated left ventricular EF (LVEF 33%). This met the criteria validated by Petersen et al., with values for sensitivity, specificity, and positive and negative predictions of 86%, 99%, 75%, and 99%, respectively . The carCurrently, there are no established guidelines by which to treat patients with LVNC. Our patient was treated similarly to a typical patient with LVNC with some modifications. The heart failure component was treated with GDMT, which included a beta-blockade, neprilysin/angiotensin receptor blocker and aldosterone antagonist. Ventricular tachyarrhythmia was addressed with an implantable cardiac defibrillator. Our thought process was as follows. If his EF remained less than 35% then he would require an automated implantable cardiac defibrillator (AICD) for primary prevention. If despite this his bradycardia persisted, we would need to consider biventricular pacemaker placement/cardiac resynchronization therapy in addition to his AICD (he would likely require greater than 40% pacing while being maintained on carvedilol). Indications for the dual-chamber cardiac defibrillator system were non-ischemic cardiomyopathy (LVNC), NYHA Class II-III CHF  and sinus node dysfunction limiting the required beta-blocker for HFrEF management.Additionally, due to the depth of trabeculations and the associated thromboembolic risk, he was continued on therapeutic anticoagulation. Patients require close and vigilant monitoring as there is increased associated morbidity and mortality. Current guidelines recommended that specific genetic testing be conducted for family members and appropriate relatives following the identification of an LV non-compaction causative mutation in the index case.Non-compaction cardiomyopathy should be considered when patients present with non-ischemic cardiomyopathy. It is important to pursue a diagnostic workup for a potential etiology of this non-ischemic cardiomyopathy. Patients with LVNC often present with heart failure and are treated the same as typical heart failure with GDMT. They are predisposed to ventricular tachycardia, possibly manifesting as syncope and as a result, they typically receive an implantable cardiac defibrillator. Due to the depth of trabeculations and increased thromboembolic risk they should be on therapeutic anticoagulation. With respect to wider impact, LVNC confers increased morbidity and mortality not only for the patient but also potentially for family members.