In 10% of cases, the cause is inherited metabolic and neuromuscular disease, chromosomic abnormalities and genetic syndromes, whereas, in the remaining 30% of patients the aetiology remains unknown.1Hypertrophic cardiomyopathy is clinically defined by the presence of increased left ventricular (LV) wall thickness that is not solely explained by abnormal loading conditions.6 The fact that LV hypertrophy is commonly heterogeneous in its distribution in HCM, challenges the use of standard methods for assessing contractile function.In everyday clinical practice, contractility and pump function are estimated using indirect measurements with 2D echocardiography that often rely on geometric assumptions where ventricular shape, wall thickness and cavity size directly influence the validity of the results.7 Even though systolic function in HCM is often locally impaired, patients often have a preserved or even supernormal EF6 as hypertrophic ventricles thicken more in absolute terms, resulting in a greater LV cavity reduction and a high values for EF.6 Furthermore, 2D echocardiography alone cannot definitely distinguish myocardial hypertrophy from interstitial infiltration and intracellular accumulation of metabolic substrates.8Although LV ejection fraction (EF) and outcome are highly associated in other clinical settings with moderately and severely impaired ventricular function, EF is not such a good predictor of outcome in LV hypertrophy.1 To meet these challenges other diagnostic tools must be utilized, including genetic testing, cardiac MRI, CT and deformation imaging with assessment of strain and strain rate.Other common diagnostic challenges include co-existent pathologies like hypertension and HCM, isolated basal septal hypertrophy in the elderly, physiological hypertrophy caused by intensive training, and presentation in the late phase of the disease with LV wall thinning.6 Normal cardiac deformation consists of longitudinal lengthening and shortening, circumferential lengthening and shortening and consequently, radial thinning and thickening n values .11Deformation can be quantified with velocity based tissue Doppler imaging (TDI) or grey scale imaging techniques like speckle-tracking echocardiography (STE). STE quantifies the deformation of the myocardium by identifying interference patterns (speckles) generated by acoustic markers in the myocardium in interaction with ultrasound waves. Displacement of these speckles can be tracked frame-to-frame during the cardiac cycle giving information about the deformation of a point in a myocardial region of interest. In each point, strains are calculated in circumferential, longitudinal, and radial directions.10, 12. Limitations of STE include lack of inter-vendor standardization13, dependence on optimal frame rates (50–90 fps) to precisely characterize regional myocardial motion14, load-dependency (preload and afterload influence the measurements15), and finally, the fact that age and gender represent a source of variation in measurements16.Compared to TDI, STE is more reproducible, less dependent on user expertise and has been validated in comparison with tagged magnetic resonance imaging17Longitudinal deformation can be measured and averaged from the three apical views, giving the value of global longitudinal strain (GLS), while the radial and circumferential deformation are measured from the parasternal short axis views giving global radial and circumferential strain. Deformational change is marked as a negative value if the tracked region shortens, meaning that in long-axis views regions with normal longitudinal contraction have a negative strain value . In shor12 If regional tracking is suboptimal in more than two myocardial segments, the calculation of GLS is not recommended.18 To reduce variability in measurement special care must be given to obtain good image quality, optimal frame rate, minimize long-axis foreshortening in apical views and ensure perpendicular imaging in short-axis views.The apical views capture a greater amount of tissue over the length of the entire myocardial wall and the images obtained are of superior resolution - making GLS the most commonly used and robust parameter to quantify cardiac deformation .12 If re6, 19 This is partly because of the multi-layered fibre orientation in the myocardium. Subendocardial fibres predominantly determine longitudinal strain, while the midmyocardial and sub-epicardial fibres mainly determine circumferential and radial strain. In numerous cardiac diseases, the sub-endocardium is the first to compromise; therefore, a decrease in longitudinal strain is the earliest indicator of pathology, often with a compensatory increase in circumferential and radial function.10 With deformation imaging, it is possible to discriminate between active myocardial segmental deformation and passive displacement of a dysfunctional myocardial segment due to adjacent segment tethering and global cardiac motion.12 Most importantly, peak systolic strain is relatively homogeneous in a healthy heart, whereas typical regional strain patterns occur in different cardiac pathologies giving room to added value in diagnostic insight into the underlying disease.In contrast to LVEF, STE assessment of longitudinal systolic deformation is a more sensitive tool in detecting early systolic dysfunction.20 The incidence of HCM is presumed to be around 1 in 500 people –making it one of the most common genetic heart diseases. Due to recent advances in genetic population studies, recognition of genotype-positive-phenotype-negative patients, clinical screening of HCM families and enhanced detection of HCM phenotype by advanced imaging, it has been suggested that the incidence may be up to 2.5-fold more common than currently presumed.2Genetic mutations of the sarcomere protein genes are inherited by an autosomal dominant pattern, with age-related penetrance and variable expressivity.21The onset of LV hypertrophy varies through life, most often occurring in adolescence, rarely in infants, young children or adults. Hence, in affected families, screening is usually initiated after 10 years of age. Age-related penetrance means that first-degree relatives should be offered follow-up assessment even when there are no definite disease-causing genetic mutations in the proband.3, heart failure4, and sudden cardiac death  - yet many patients achieve normal life expectancy. Sudden cardiac death (SCD) is a rare but calamitous outcome, more common in the <30-year-old patient subgroup. With regards to treatment interventions , the expected annual mortality rates in adult HCM patients have reached a low 0.5%, as compared to previously expected rates of about 1.5%/year.5Patients have a variable clinical presentation and natural course. Outcomes include thromboembolism22 resulting in increased regional wall thickness, increased LV mass, and impaired cardiac mechanics in hypertrophic segments23. As previously mentioned, until the end-stages of the disease, LVEF is mostly preserved or even supernormal in patients with HCM.HCM caused by sarcomere protein mutations is characterized by disruption of myocardial architecture, cardiomyocyte hypertrophy, fibre disarray and patchy interstitial fibrosis6 Strains can be abnormal in mutation-positive patients even before any thickening of the myocardium is seen with conventional echocardiography.23 In HCM, the reduction in GLS proved to be an independent factor associated poor cardiovascular outcomes - most strongly with heart failure.24, 25The greatest reduction in longitudinal strain is seen at the site of hypertrophy, most often in the interventricular septum , while rTypically, in HCM patients there is a significant heterogeneity in regional myocardial deformation and wall thickness, with areas of normal deformation within areas of abnormal deformation in the same ventricular region, a finding possibly related to the heterogeneous distribution of myocardial disarray in HCM. To evaluate this, the colour-coded Doppler Tissue Imaging is particularly useful as it can readily depict the deformation of myocardial areas within adjacent ventricular segments . ImpairmHypertrophy of the LV in the setting of increased afterload is the response of the myocardium to a continuously increased ventricular wall stress. The pressure inside the ventricle is transferred to the myocardial wall dependent on the local geometry. Because of the variable local radius of curvature of the myocardial walls, the wall stress is heterogeneously distributed on different LV segments. Wall stress triggers the activation of a compensatory mechanism of myocardial remodelling resulting in gradual wall thickening over time.1 Unlike HCM, there is no myofibril alignment disarray in regions with hypertrophy. With regulation of blood pressure in hypertensive patients, a regression of LV hypertrophy can be seen, an effect not seen in HCM.Arterial hypertension is an example of increased afterload, over time resulting in concentric hypertrophy of the LV coupled with diastolic dysfunction and increased LV filling pressures. The wall thickness in hypertensive hypertrophy is influenced by ethnicity, neurohumoral factors and genetic variants, but in the majority of patients maximal interventricular septal thickness is less than 15 mm.In cases of high blood pressure, due to the increased local radius of curvature, the basal septal segment is the first to show subclinical systolic dysfunction, quantifiable by changes in deformation - decrease in longitudinal strain  and typi26 With persistent systemic hypertension or overload, gradually all other segments will develop hypertrophy and will show a decrease in LS.Post-systolic thickening results from the localized increased wall stress in the basal septum that typically has a reduced deformation and increases deformation when load decreases, after the closure of the aortic valve. These findings can precede the increase in regional wall thickness - also known as ‘septal bulging’  – and th27 However, in a study comparing patients with hypertensive hypertrophy to HCM patients, a significantly higher GLS was found in hypertensive patients (−17.8 ± 3.1% vs −11.2 ± 4.2%).28Hypertensive hearts might ultimately present with a reduced GLS in advanced stages of the disease with persisting poor-controlled hypertension, the magnitude of which is associated with diastolic dysfunction, independent on afterload changes and degree of LVH.29 This is in contrast to HCM, where hypertrophy occurs at the expense of cavity size leading to a small LV end-diastolic volumes6, 29.The term ‘athlete’s heart’ is often used to describe the adaptation of the heart to long-term physical activity and related haemodynamic overload. In athletes predominantly participating in isotonic or endurance training, a combination of decreased peripheral resistance and increased venous return results in increased preload and chronic volume overload. Over time, these changes lead to eccentric LV hypertrophy with increased wall thickness and LV mass, coupled with proportionally increased LV end-diastolic volumes.30, although 2% of highly trained athletes develop wall thickness between 13 and 15 mm31. In some athletes with dimensions above these upper limits there is a phenotypical overlap with lower levels of disease penetrance in HCM, thus defining a grey zone between physiology and pathology. In these cases, a pragmatic method of resolving clinical dilemmas can be applied including a prolonged period of detraining, where reduction of wall thickness may be a sign of physiological hypertrophy . Caselli et al.33 evaluated 200 Olympians demonstrating normal GLS and strain rate in highly trained athletes. Even in 5 athletes demonstrating wall thickness of more than 13 mm, there was no difference in GLS or strain rate as compared to the rest of the cohort. Therefore, reduction in GLS is not considered a part of physiological adaption to training.In a study comparing patients with HCM to professional athletes34However, more than the absolute value of GLS, it is important to analyse the distribution and the pattern of myocardial deformation to differentiate true from hypertrophic adaptation to training. Typically, in HCM patients there are areas of normal deformation within areas of abnormal deformation, potentially related to myocardial disarray in HCM. These findings are not present in physiological, adaptive, hypertrophy of athletes. Therefore, in athletes, any sign of LV hypertrophy coupled with significantly reduced strain values should be evaluated carefully and considered as a potential true HCM and not only physiological adaptation.35 In cardiac transthyretin amyloidosis (TTR) - due to amyloid fibrils from liver-derived transthyretin - the heart is involved less frequently and heart symptoms occur at older ages.1 Deposits induce oxidant stress and lead to myocardial necrosis and interstitial fibrosis resulting in systolic and diastolic dysfunction.10In systemic light chain amyloidosis (AL) - due to a clonal plasma cell disorder - the heart is involved in 50% patients; the symptom progression is most commonly rapid and mortality higher compared to other types of amyloidosis.36In cardiac amyloidosis, the myocardium has a granular appearance. There is progressive hypertrophy of both ventricles usually coupled with a normal LV cavity size, whereas the atria are bilaterally enlarged with a thickened interatrial septum due to the restrictive ventricular physiology. Thickening of the mitral and tricuspid valves may also be seen . A study37Buss et al.38 describe reduced LV longitudinal function assessed by GLS to be an independent predictor of survival in AL amyloidosis (survivors vs. nonsurvivors −13.1 ± 5.4% vs. −9.8 ± 4.4%). Using deformation imaging, LV dysfunction can be detected prior to any signs of morphological or functional impairment as assessed by 2D-echocardiography or assessment of diastolic function.39Morphologic traits raise suspicion, but are not sensitive or specific enough to make a diagnosis. A reduction in longitudinal systolic strain can be seen globally, though most prominently in the basal segments . Commonl40 Alongside renal disease and stroke, heart disease has become the leading cause of mortality in affected individuals, usually manifesting as mitral and aortic leaflet thickening coupled with regurgitation, LV hypertrophy, diastolic dysfunction, arrhythmias, heart failure, and sudden cardiac death.41Anderson-Fabry disease (AFD) is a lysosomal storage disease caused by an X-linked disorder resulting in deficiency of the enzyme alpha-galactosidase A. This deficiency leads to intracellular globotriaosylceramide (Gb3) accumulation in tissues throughout the body - in the heart, kidneys, central nervous system amongst others - resulting in a variable, often non-specific, combination of signs and symptoms.Disease severity depends on enzyme activity, which differs in two major phenotypes of the disease. In classic AFD the enzyme activity is absent or below 5% resulting in symptoms beginning in early childhood, whilst cardiac involvement becomes relevant between 20 and 40 years of age.40 Similarly, as seen in other aetiologies of LV hypertrophy, in a majority of patients with AFD the systolic function is preserved when assessed by EF.42 In addition, only 40% of patients have LV hypertrophy at the time of diagnosis.43 Therefore assessment of cardiac involvement is challenging with conventional echocardiography. Deformation imaging can detect subclinical impairment of contractile ability before LVH occurs44 and help monitor the efficiency of treatment. In the early stage of disease, in patients without high levels of myocardial fibrosis, enzyme replacement therapy proved to be effective in reducing Gb3 accumulation in the myocardium, reducing LV mass and improving cardiac function assessed by deformation imaging.45Lysosomal Gb3 deposits make up only 3% of the mass of the hypertrophic heart, however, the deposition induces oxidative stress and inflammation resulting in hypertrophy and remodelling of the extracellular matrix.46 observed a consistent pattern of myocardial fibrosis characterized by a mid-myocardial distribution sparing the sub-endocardium, most commonly involving the inferolateral basal or mid-basal segments - findings potentially specific to AFD. Deformation imaging can also depict the typical pattern of distribution of lower longitudinal strain mainly involving the inferolateral segments of the LV. Moreover, several studies47, 48 demonstrated that while longitudinal strain was impaired in both AFD and HCM (On a CMR study with a sample of 13 AFD patients, De Cobelli et al. and HCM , circumfThere is a wide spectrum of differential diagnoses for hypertrophic ventricles Different pathologies result in different timing and distribution of cardiac involvement, resulting in different patterns of regional impairment. Deformation imaging contributes to the identification of this underlying aetiology through the visualization of disease specific strain patterns.


We report a case of hantavirus-induced myocarditis in a young adult. Hantavirus showed a rapid increase of infections in the year 2017. Only scarce data is available about potential myocardial involvement in hantavirus infections. With ECG and echocardiography providing often inconclusive results, a multiparametric cardiac magnetic resonance protocol with distinct myocardial tissue characterization seems to be the adequate tool for detecting even slight myocardial alterations.This case started with the presentation of young adult suffering from headache and abdominal pain. Thrombocytes were decreased, creatinine was elevated, and there was massive proteinuria. Puumala virus IgG ELISA turned out to be positive, and specific antibodies (IgG and IgM) could be detected in the serum, and confirmed by immunoassay. The patient was admitted to the nephrology department for supportive therapy. Few days later, the patient reported chest pain and dyspnea. High sensitivity troponin I rose up to 0.32 μg/l  with an increase of the creatinkinase to 319 U/l , no dynamic ECG changes could be observed. Echocardiography revealed a normal left ventricular function without regional wall motion abnormalities, no pericardial effusion or valve abnormalities, coronary artery disease could be excluded by computed tomography. A multiparametric cardiac magnetic resonance protocol including recent mapping techniques confirmed myocardial involvement induced by acute hantavirus infection. In the next few weeks, the patient’s state of health rapidly improved and symptoms of chest pain and dyspnea disappeared. Follow up multiparametric CMR exam showed substantial decrease of the previously observed myocardial alterations during acute hantavirus infection suggesting myocardial healing.This case demonstrates that a CMR protocol including recent mapping techniques and established late gadolinium enhancement technique is an adequate non-invasive tool for both 1) initial detection, and 2) follow up of patients with hantavirus-induced myocarditis, which might be more common than previously known.The online version of this article (10.1186/s12879-018-3658-8) contains supplementary material, which is available to authorized users. There was a substantial increase in hantavirus infections in 2017. Although primarily affecting the kidneys, this case draws attention to the fact that hantavirus might also involve the myocardium resulting in hantavirus-induced myocarditis which can be adequately 1) detected, and 2) followed by the use of a comprehensive cardiovascular magnetic resonance (CMR) assessment since CMR has proven high diagnostic value for detection of various myocardial pathologies, including patients with suspected myocarditis, cardiac sarcoidosis and other forms of non-ischemic cardiomyopathies [A 36-year-old white male patient suffering from headache and abdominal pain presented at our emergency department. Initial ECG showed a sinus rhythm (40/min.) with a single T-wave inversion in lead V2, and an incomplete right bundle branch block. Thrombocytes were decreased with 71.000/μl , creatinine was elevated (2.0 mg/dl) with a maximum increase to 3.0 mg/dl  and massive proteinuria. C-reactive protein was also elevated: 8.6 mg/dl . Puumala virus IgG ELISA turned out to be positive, and specific antibodies (IgG and IgM) could be detected in the serum, and confirmed by immunoassay, also see Additional file Six days later, the patient reported chest pain and dyspnea. High sensitivity troponin I rose up to 0.32 μg/l  with an increase of the creatinkinase to 319 U/l , no dynamic ECG changes could be observed. The patient was admitted to the chest pain unit. Echocardiography revealed a normal left ventricular function (65%) without regional wall motion abnormalities, no pericardial effusion or valve abnormalities. Since creatinine has normalized in the meantime, coronary artery disease was ruled out by coronary CT angiography.1-mapping and performed in a single mid-ventricular short-axis (SAX) slice at mid-diastole, prior and after application of contrast agent according to current recommendations [2-mapping was performed in the corresponding mid-ventricular SAX before administration of contrast agent using an ECG-triggered T2-prepared single-shot steady-state free precession (SSFP) product sequence with multiple T2 preparation times [CMR for work-up of suspected myocarditis was performed using a 1.5 T Magnetom Aera . Cine-SSFPs revealed normal LV-EF (60%) with no wall motion abnormalities. A modified Look-Locker inversion recovery product sequence  was used for Tndations . T2-mappon times . Normal 1-mapping demonstrated markedly elevated T1 values with preponderance in the inferoseptal wall , also see Figs. 2-mapping revealed increased values , suggesting myocardial edema representing active myocardial inflammation by hantavirus infection. In contrast, the LGE image, potentially indicating irreversible myocardial damage if positive, in the corresponding slice was negative  and T2 values  in the mid-ventricular slice position could be observed, again LGE-negative, suggesting myocardial healing  is useful in discriminating between both stages. Therefore, it seems reasonable to combine LGE as well as T1-mapping and T2-mapping techniques performing a comprehensive CMR assessment [Myocardial inflammation leads to hyperemia with development of intracellular and interstitial edema, sometimes yielding irreversible myocyte damage, which can be visualized accurately by LGE. However, tissue edema without irreversible myocyte damage cannot be displayed by LGE. Furthermore, the value of LGE in displaying diffuse myocardial alterations is limited. Therefore, the sensitivity may be increased by combining LGE with recent Tsessment .1- and T2-mapping techniques, which can detect also diffuse myocardial alterations by quantitative means in absolute values and can better separate between fibrosis and edema, and 2) established LGE, appear as the most reasonable non-invasive approach in patients with suspected myocarditis for both initial diagnosis and follow-up.Although endomyocardial biopsy is the gold standard for diagnosis in suspected myocarditis it is invasive and might suffer from the sampling error. ECG and echocardiography are ubiquitous available and still the method of choice for initial evaluation of potential myocardial damage but these lack specificity. Thus, a comprehensive CMR approach consisting of 1) recent TTo the best of our knowledge, this is the first case demonstrating the benefit of a comprehensive CMR exam in a patient presenting with acute hantavirus-induced myocarditis. This case demonstrates that a CMR protocol including recent mapping techniques and established LGE is an adequate non-invasive tool for both 1) initial detection, and 2) follow up of patients with hantavirus-induced myocarditis, which might be more common than previously known.Additional file 1:Figure S1. The recomLine HantaPlus IgG, IgM line immunoassay from Mikrogen  detects Puumala Virus (PuN), Sin Nombre Virus (SinN), Hantaan Virus (HaN), Dobrava Virus (DobN) and Seoul Virus (SeoN). The assay detects the serotype specific N-terminal part of the virus nucleocapsid antigen. This test provided strong evidence for infection with Puumala Virus (IgG and IgM strong positive) in our patient. (PPTX 297 kb)


Twist and rotation were determined using an in-house developed post-processing pipeline. Global deformation indices  were significantly lower in patients with LVNC compared to healthy controls , especially for midventricular and apical regions. Apical rotation and twist were impaired for LVNC (p = 0.007 and p = 0.012), but basal rotation was preserved. Deformation indices of strain, strain rate and twist correlated well with parameters of the non-compacted myocardium, but not with the total myocardial mass or the thinning of the compacted myocardium, e.g. r = 0.595 between GLS and the non-compacted mass (p < 0.001). In conclusion, CMR deformation indices are reduced in patients with LVNC especially in affected midventricular and apical slices. The impairment of all strain and twist parameters correlates well with the extent of non-compacted myocardium.Clinical presentation of left ventricular non-compaction cardiomyopathy (LVNC) can be heterogeneous from asymptomatic expression to congestive heart failure. Deformation indices assessed by cardiovascular magnetic resonance (CMR) can determine subclinical alterations of myocardial function and have been reported to be more sensitive to functional changes than ejection fraction. The objective of the present study was to investigate the determinants of myocardial deformation indices in patients with LVNC. Twenty patients with LVNC (44.7 ± 14.0 years) and twenty age- and gender-matched controls (49.1 ± 12.4 years) underwent functional CMR imaging using an ECG-triggered steady state-free-precession sequence (SSFP). Deformation indices derived with a feature tracking algorithm were calculated including end-systolic global longitudinal strain (GLS), circumferential strain (GCS), longitudinal and circumferential strain rate (SR As a result, it is phenotypically characterized by a thin, compacted epicardial layer in contrast to a prominent non-compacted endocardial layer with multiple trabeculations and deep intertrabecular recesses. Diagnosis of LVNC is usually made using transthoracic echocardiography (TTE) as main diagnostic tool by describing the compacted thin epicardial layer and a thicker-non-compacted endocardial layer with a ratio between non-compacted to compacted myocardium >2 in end-systole of a short-axis slice, a predominant localization in midventricular and apical segments and perfused intertrabecular recesses2. Cardiovascular magnetic resonance (CMR) is frequently used to confirm or rule out the diagnosis.Left ventricular non-compaction cardiomyopathy (LVNC) is a congenital cardiomyopathy that arises from a premature arrest of myocardial compaction during embryogenesis3. While left ventricular ejection fraction (LVEF) represents one parameter to assess myocardial function, there is growing evidence that the assessment of myocardial deformation indices (strain parameters) provides additional information in the clinical setting.As clinical manifestation of LVNC can be heterogeneous potentially leading to chronic heart failure or ventricular arrhythmias, reliable follow-up strategies are warranted6. This indicates that strain parameters are more sensitive to functional changes of the heart. As CMR deformation analysis using feature tracking algorithm can be derived from standard, cine steady-state-free precession (SSFP) images without the need for additional, time-consuming sequences and due to its reproducible, in-plane image acquisition this approach may have potential advantages. From hypertrophic cardiomyopathy it is known that CMR strain indices can already be reduced even when LVEF is normal or supernormal and that they may also yield prognostic information for patients with dilated cardiomyopathy or myocardial infarction9.Strain parameters as assessed by speckle tracking echocardiography have already shown reduced values for patients with LVNC even when LVEF was preserved10, the aim of the present study was to investigate in addition also strain rate and twist in LVNC patients as well as regional strain parameters and to determine their correlation with morphological aspects of LVNC.As a recent study indicated that CMR-based GLS, GCS and GRS were impaired in LVNC patientsThe study was conducted in accordance to the Declaration of Helsinki and its later amendments. The study design was approved by the Ethics Committee of the Canton of Zurich and written informed consent was obtained. All data used for this study were handled anonymously.11. TTE parameters defined the non-compacted to compacted ratio > 2 in systole in a short-axis view predominantly localized in midventricular and apical segments with additional color Doppler evidence of perfused intertrabecular recesses as well as absence of coexisting cardiac abnormalities2. CMR diagnostic criteria defined the ratio of the thickness of LV non-compacted myocardium to compacted myocardium as greater than 2.3 in any long-axis view during diastole11. The LVNC group as well as 20 additional age- and gender-matched healthy controls received CMR.In total, 20 patients with LVNC were prospectively included into this study from our outpatient clinic, between October 2011 and July 2016. Before the acquisition of the CMR, the enrolled patients had been diagnosed with LVNC according to current recommendations for transthoracic echocardiography (TTE)3, 2 slices per breath-hold, minimum phases: 25). Late gadolinium enhanced imaging 15 minutes after contrast agent  administration was performed in order to detect myocardial scarring or fibrosis. Therefore, a gradient-spoiled turbo fast-field-echo sequence with a non-selective 180° inversion pre-pulse was acquired at end-diastole with anatomical reference taken from SSFP images.Imaging was conducted on a 1.5 T MR imaging system  using a 5-channel phased array coil. After scout and reference scans, functional and geometric assessment was achieved by electrocardiogram-triggered, cine steady-state-free precession (SSFP) images in standard long-axis geometries  as well as in short-axis orientation with full ventricle coverage from basis to apex (repetition time (TR)/echo time (TE) = 3.3/1.6 ms, flip angle (FA) = 60°, spatial resolution = 8 × 1.5 × 1.5 mm12. In addition, the end-diastolic extent of compacted (LV-C) and non-compacted (LV-NC) myocardium as well as their ratio were measured in one long axis geometry (LV-NC/C)11.CMR analyses were performed using GTVolume . Standard analysis of functional and geometric LV indices was obtained including left and right ventricular end-diastolic volume (LVEDV/RVEDV), left and right ventricular ejection fraction (LV-/RV-EF), indexed left ventricular compacted mass with papillary muscles (LVMi-C), indexed left ventricular compacted and non-compacted mass (LVMi-MM), indexed left ventricular non-compacted mass (LVMi-NC) as well as their ratio (LVMi-NC/MM)13. Cine images in long- and short-axis view were used for the analyses of end-systolic global longitudinal (GLS) and global circumferential (GCS) strain of the left ventricle, a global right ventricular longitudinal strain (RV-GLS) and longitudinal (SRll) as well as circumferential (SRcc) peak diastolic strain rate. For strain analysis, endocardial contours were manually drawn independent of the cardiac cycle followed by subsequent software-driven automatic tracking of image features, such as tissue patterns or signal inhomogeneities  was achieved by repeating strain analysis on 28 randomly chosen subjects (14 LVNC and 14 controls).Myocardial feature tracking (FT) analysis was performed using TomTec software  on the basis of a previously established algorithm14.In addition to strain parameters, peak apical and basal rotation as well as the end-systolic twist was obtained. End-systolic twist was defined by the subtraction of minimum basal rotation, obtained around end-systole, from maximum apical rotation around end-systoleAs a result of unsatisfactory low reproducibility of the rotation parameters determined with the commercially available software, a custom-built, post-processing pipeline was built in-house to aim for more reproducible rotation parameters from short-axis cines images.16. The algorithm does not require myocardial segmentation and receives as an input N cine images that correspond to the different cardiac phases. The regularized registration problem is solved by estimating N spatial image transformations that minimize the nuclear norm of image patches. Such group-wise image similarity metric allows to non-parametrically enforce image alignment via patch correlation17. For the current short-axis images, cubic image interpolation was used, linear splines for displacement parametrization with grid stride of 4 pixels, L1-regularization of second order displacement derivatives in temporal domain with the weight of 5·10–3, vectorial total variation regularization in the spatial domain with weight of 5·10–2. Estimated displacement fields were then used to deform myocardial contour between different cardiac phases, e.g. displacement fields that map phase t to phase 0 were used to propagate the contour at phase 0: ct = c0 ° τt,0, (e.g end-systole to end-diastole).Dense motion fields via image registration were estimated using a previously established algorithm publicly available as Matlab toolboxsl, and mean in-plane width sw was calculated. Circumferential  U-test for not normally distributed data. For post-hoc analyses, the LVNC patient group was divided into two subgroups with either preserved (LVEF ≥ 50%) or reduced (LVEF < 50%) systolic function.Statistical analysis was performed using SPSS 24.0 . Unless otherwise stated, continuous variables are presented as mean ± standard deviation (SD). Normal distribution was tested using the Shapiro-Wilk test. Categorical variables are reported as percentage. Data between the two different groups were analyzed by 2-sided unpaired Student’s t-tests for normally distributed data and Mann-Whitney 2 test was used to examine significant differences between nominal classifications. For intra- and interobserver agreement, coefficients of variation (CoV) were calculated by dividing the SD of the differences by the mean. In addition, intraclass correlation coefficients (ICC) were assessed using a model of absolute agreement. There was excellent agreement when ICC > 0.74, good when ICC = 0.60–0.74, fair when ICC = 0.40–0.59, and poor when ICC < 0.419.χPearsons correlation was performed to calculate correlations between functional and geometric CMR parameters. Two-tailed p-values below 0.05 were considered statistically significant.20 LVNC patients (mean age 44.7 ± 14.0 years) were included into this study. The age- and sex-matched 20 healthy control subjects showed similar body surface area (BSA) characteristics. Further clinical baseline characteristics are summarized in Table 20. Eight LVNC patients showed a (mid-range) reduced LVEF with values < 50%. Despite no difference in LVMi-C, there were significantly higher values in non-compacted parameters as well as their ratios for patients with LVNC. No differences could be seen for RV functional and geometric indices.LVNC patients had a significantly lower LVEF in comparison to the controls Table , but accFeature tracking analysis revealed significantly lower GCS and GLS values for the LVNC group compared to controls . On a regional level, GLS parameters were not different for basal and midventricular segments, but for apical ones Fig. . For GCSBesides a correlation with LVEF, further correlation analyses revealed that GLS best correlated to parameters including the noncompacted areas Table , such asMean differences ±1.96 SD, CoV and ICC for GLS and GCS divided by control and diseased groups are summarized in Table As a second result of the newly-developed tool to analyze rotational parameters, GCS was calculated as well. There was a significant difference in global GCS for LVNC . Statistical significance of differences increased again from basal , to midventricular  and apical GCS . In addition, there was excellent intraobserver reproducibility for the healthy  and diseased group . Interobserver reproducibility showed similar results .ll and SRcc were significantly lower for LVNC compared to controls . In post-hoc Bonferroni correction, this difference only remained for the comparison of controls and patients within the subgroup of reduced LVEF (p = 0.004), but not between the two subgroups. For SRcc, ANOVA indicated a difference between the groups as well (p < 0.001), which was most pronounced between controls and patients within the subgroup of reduced LVEF (p < 0.001), less pronounced between the two subgroups (p = 0.004). There was no difference between controls and patients within the subgroup of preserved LVEF. Like for strain, three patients with LGE presented with SRll and SRcc below the mean of the LVNC group.Like GLS and GCS, peak diastolic SRols Fig. . On a reRcc Fig. . ANOVA all and SRcc to parameters of the non-compacted myocardium, such as LV-NC or LVMi-NC  and 101.9% (ICC = 0.65) for intra- and interobserver agreement for the healthy group and 98.6 (ICC = 0.35) and 98.0% (ICC = 0.34) for the diseased group. Results for the apical rotation showed a CoV of 65.2% (ICC = 0.68) and 72.2% (ICC = 0.77) for the healthy, and 51.7 (ICC = 0.55) as well as 46.7% (ICC = 0.68) for the diseased group.The in-house written MATLAB-based script showed excellent reproducibility for rotational parameters in the healthy and diseased groups (ICC 0.95–0.99) Table . ReproduAnalyses showed that there was no difference in basal rotation, but a significant difference in maximum apical rotation with lower values for the LVNC group (p = 0.007) Fig. . This diSimilar to strain values, twist correlated well with parameters of the non-compacted myocardium, e.g. LV-NC/C  Table .Table 6Cll and SRcc were found to be significantly impaired in LVNC, especially in midventricular and apical segments with a good correlation to parameters of the non-compacted myocardium. By implementing a software for assessing ventricular rotation, impaired apical rotation and twist with good reproducibility could be shown as well.The present study provides CMR myocardial deformation indices in patients with LVNC compared to controls on a global and regional level. GLS and GCS, as well as SR22. Besides TTE, CMR is frequently used to confirm the diagnosis of LVNC or for follow-up strategies. As additional parameter to LVEF, CMR-derived strain can easily be assessed by post-processing standard cine images without the need for further sequences like tagging, or displacement-encoding (DENSE). In addition, CMR yields the advantage of a reproducible, in-plane image acquisition. Therefore, these parameters can be of additional value for the description of functional changes in LVNC23.During its heterogeneous course, LVNC may lead to heart failure or arrhythmic events14. In addition, a global strain reduction has already been shown in a CMR study of children and adolescents with LVNC10. However, the disease is mainly manifested in apical and midventricular regions which is mirrored in regional CMR-derived strain parameters for the first time. This can be underlined by the new correlation of strain parameters to indices of noncompacted masses2. Therefore, GLS is preserved in basal regions , which is comparable to literature25. Due to the still preserved basal rotation, a previously described ‘solid body rotation’ with near absent LV twist could not be confirmed in the present study14. This may be influenced by the different image planning of TTE and CMR. Reproducibility was poorest for diseased patients in apical rotation. Given that the disease mainly affects midventricular and apical regions with lower values, the higher CoV is not surprising2.As already shown using only speckle-tracking echocardiography so far, apical rotation and twist was impaired in LVNC11. However, this limited population already showed promising data for the description of myocardial strain indices in patients with LVNC and was comparable to patient numbers previously published in the literature14.As the incidence of LVNC in the normal population is low, a limitation of the current work is the relatively small sample size of patients with LVNC, especially for the division according to an LVEF threshold18. In contrast, echocardiographic speckle tracking based assessment of layered strain has already shown different subendo- and subepicardial dynamics in patients after aortic valve replacement26. Since LVNC is considered to have differential impact on the myocardial layers, an investigation of the transmural variation of strain would be of interest for future studies.As an inherent limitation, FT algorithms can only distinguish the endo- or epicardial interfaces of the myocardium and are, therefore, unable to assess transmural variations of the myocardial strain24.In addition, global radial and segmental strain were not obtained due to recent evidence of their lower reproducibilityCMR deformation indices including GLS, GCS and strain rate parameters were reduced in patients with LVNC especially in affected midventricular and apical slices and correlated well with parameters of the non-compacted myocardium. By using a novel approach for post-processing CMR data, reduced twist and apical rotation with a good reproducibility could be shown. CMR-derived deformation indices may show added value to assess functional impairment in LVNC, even when LVEF is preserved.


Since the discovery of dissimilar ventricular tachyarrhythmias using implantable cardioverter defibrillators (ICD) with cardiac resynchronization therapy (CRT-D) with the capability of left ventricular electrogram (EGM) recording , it was ex vivo Perfused Hearts”, Handa et al. used rat hearts to investigate the inducibility of dissimilar rhythms, the impact of antiarrhythmic drugs and the underlying mechanism , which can lead to serious complications in correct ICD detection and the delay or absence of therapy. Momentarily, the detection of ventricular tachyarrhythmias (VAs) is exclusively based on the implanted electrode in the RV. A correct ICD detection cannot be expected if the RV rate is below the programmed cut-off rate, although ventricular fibrillation (VF) exists in the left ventricle.The results in the above mentioned study  have shoHowever, in other CRT-D recordings  we obserFrequently, dissimilar ventricular rhythms will be triggered by anti-tachy pacing, intraoperative induction shocks or ineffective therapeutic shocks. It is rather rare that such heart rate disparities occur spontaneously. In the prehistory of the EGM recording (not shown in In our experience, the probability of discovering RV>LV is even higher than the incidence of LV>RV discovery, possibly because RV>LV can be better detected and treated by the ICD compared to LV>RV. A dynamic dual-side detection principle would certainly be an interesting idea. However, it can only be a possible concept in CRT-D devices. It is unfortunately not applicable in the single- or dual-chamber ICDs because of the absence of LV sensing , 4. FurtIt is remarkable that the phenomenon of RV>LV was not observed in the present study. Perhaps these cases of RV>LV could not be triggered due to the fact that this is an animal study and conditions other than those found in humans may prevail. The authors should be commended for their elegant study looking into the physiological mechanism of dissimilar rhythms, thereby lending support for clinical observations. It would be of great scientific interest if the authors can be encouraged to continue their efforts and expand their research to both observations of LV>RV as well as RV>LV, to reproduce them in the lab.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.AK is an employee of BIOTRONIK SE & Co. KG. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Both ischemic and non-ischemic heart disease can cause disturbances in the myocardial blood volume (MBV), myocardial perfusion and the myocardial extracellular volume fraction (ECV). Recent studies suggest that native myocardial T1 mapping can detect changes in MBV during adenosine stress without the use of contrast agents. Furthermore, native T2 mapping could also potentially be used to quantify changes in myocardial perfusion and/or MBV. Therefore, the aim of this study was to explore the relative contributions of myocardial perfusion, MBV and ECV to native T1 and native T2 at rest and during adenosine stress in normal physiology.n = 41, 26 ± 5 years, 51% females) underwent 1.5 T cardiovascular magnetic resonance (CMR) scanning. Quantitative myocardial perfusion [ml/min/g] and MBV [%] maps were computed from first pass perfusion imaging at adenosine stress (140 microg/kg/min infusion) and rest following an intravenous contrast bolus . Native T1 and T2 maps were acquired before and during adenosine stress. T1 maps at rest and stress were also acquired following a 0.2 mmol/kg cumulative intravenous contrast dose, rendering rest and stress ECV maps [%]. Myocardial T1, T2, perfusion, MBV and ECV values were measured by delineating a region of interest in the midmural third of the myocardium.Healthy subjects . Myocardial perfusion, MBV and ECV all correlated with both native T1 and native T2, respectively .During adenosine stress, there was an increase in myocardial native T1, native T2, perfusion, MBV, and ECV , and native T1 .Multivariate linear regression revealed that ECV and perfusion together best explained the change in native T2 (ECV beta 0.21, Myocardial native T1, native T2, perfusion, MBV, and ECV all increase during adenosine stress. Changes in myocardial native T1 and T2 during adenosine stress in normal physiology can largely be explained by the combined changes in myocardial perfusion and ECV.Clinicaltrials.gov identifier NCT02723747. Registered March 16, 2016. Coronary artery disease (CAD) and several other non-ischemic heart diseases affect the myocardial microcirculation . AccuratParametric pixel-wise mapping has been developed to quantitatively measure and image the longitudinal relaxation time constant (T1) , and then = 43, 26 ± 5 years, 51% females) were included if they had no use of cardiovascular medication and had no previous history of cardiovascular symptoms or systemic disease, kidney disease, or asthma, were current non-smokers, and had a normal 12-lead electrocardiogram (ECG). The 12-lead ECG and a venous blood sample, used to determine blood hematocrit, were collected immediately prior to the CMR exam. Exclusion criteria included failed splenic switch off [Clinicaltrials.gov identifier NCT02723747.Healthy subjects  1.19 ms, repetition time(TR) 2.85 ms, matrix size =144 × 256, and field of view (FOV) 360 × 270 mm2.CMR was conducted at 1.5 T  with a phased-array eighteen-channel body matrix coil together with a spine matrix coil. All patients were examined in the supine position. Figure 2, slice thickness 8.0 mm and parallel acquisition technique factor 3.Three short-axis slices  were acquired during first pass perfusion imaging, both during adenosine stress  and at rest, during administration of an intravenous bolus of contrast agent . Adenosine was administered in one cannula, while the contrast agent was administered in a separate cannula in the opposite arm. All maps were automatically generated using inline perfusion software implemented in the Gadgetron online reconstruction framework  and the 2, slice thickness 8.0 mm, imaging duration 167 ms, TE/TR 1.12 ms/2.7 ms, matrix size =144 × 256, FOV 360 × 270 mm2 and breath hold 10.7 s. Three rest and stress ECV maps were generated offline from rest pre- and post-contrast T1 maps, and stress pre- and post-contrast T1 maps, respectively, and calibrated by blood hematocrit [Three short axis native myocardial T1 maps  were acquired using an ECG-gated modified Look-Locker inversion recovery (MOLLI) sequence  with a 5matocrit , employimatocrit .2, slice thickness 8.0 mm, acquisition window 700 ms, TD 483 ms, matrix size = 144 × 256, acceleration factor = 2. Inline motion registration was performed followed by a pixel-wise parametric fit to estimate the final T2 maps.Three myocardial native T2 maps  were acquired before and during adenosine stress (140 microg/kg/min infusion). T2 mapping was performed using the Siemens MyoMaps product sequence, which is a T2-prepared sequence. The T2 map was calculated from 3 single-shot acquisitions at different T2 preparation times . Typical imaging parameters included TE/TR = 1.06/2.49 ms, FA 70°, pixel size 1.4 × 1.4 mmThe subjects did not undergo late gadolinium enhancement (LGE) imaging as focal myocardial scar from silent myocardial infarction or myocarditis would be visible in rest ECV maps.Apical stress ECV maps were not of sufficient quality due to partial volume effects, and a sizable portion of the basal stress ECV maps were affected by the more prominent through-plane motion associated with imaging at a higher heart rate during stress. Thus, only the midventricular images were analyzed. The midventricular native T1, native T2, perfusion, MBV and ECV maps were analyzed with Segment software version 2.0 R5152 . All the respective average values were acquired by conservative manual delineation of a circumferential region of interest in the midmural third of the myocardium in the respective maps, both at rest and stress. To assess reproducibility, segmental analysis of the respective maps was performed by 3 independent observers.LV volumes, ejection fraction and myocardial mass were quantified using the SyngoVia Software, VA30 , including manual corrections. Body surface area (BSA) was calculated with the Dubois formula . Volumet2. Significant univariate associations were entered into the multivariate linear regression analysis. Multivariate linear regression was assumed for native T1 and native T2, respectively, and was used to investigate the best explanatory parameters for native T1 and native T2, respectively, using manual stepwise linear regression modeling. By combining rest and stress absolute values in the same data set, the absolute changes in all parameters were investigated by linear regression. Mean values were compared by using the paired or unpaired t-test as appropriate in normally distributed data, as decided by the Kolmogorov-Smirnov test. Interobserver variability was assessed by intraclass correlation. Intraobserver variability was calculated as the average difference of two measurements divided by their mean, and expressed as a percentage. Statistical analysis was performed using Microsoft Excel®  and SPSS Statistics® , International Business Machines, Inc., Armonk, New York, USA). The significance level in all statistical analyses was defined as p < 0.05.Continuous variables were reported as means together with their standard deviation (SD). Ordinal variables were reported as percentages. The relationships between perfusion, MBV, ECV, heart rate, systolic blood pressure, rate pressure product and hematocrit, and native T1 and native T2, respectively, were assessed with Pearson’s linear correlation coefficient, and presented as Rn = 1, and low peak AIF, n = 1). Table n = 41). Stress ECV images could not be processed in 4 cases because pre and post T1 maps were mistakenly acquired with different FOV, and these cases were excluded from analysis of ECV. No subjects had any evidence of any focal myocardial scarring in any of the three short-axis maps. No subject was excluded due to poor image quality.In total, two of the healthy subjects were excluded , native T2 , MBV , myocardial perfusion , and ECV , see Fig. From rest to stress there was an increase in native T1 , Fig. p = 0.02; perfusion beta 0.66, p < 0.001, model R2 = 0.64, p < 0.001), and change in native T1 , Table The relationships between myocardial T1, T2, MBV, perfusion and ECV assessed individually at rest and stress, respectively, are presented in Additional file We demonstrate that native myocardial T1, native myocardial T2, myocardial perfusion, MBV, and ECV all increase in response to adenosine stress in healthy subjects. The changes in native myocardial T1 and T2 values are best explained by the combined changes in myocardial perfusion and ECV, thus supporting the notion that native myocardial T1 mapping, and T2 mapping indeed reflect the increase of blood in the myocardium during adenosine stress, and illustrating the mechanism behind the potential to use native T1 or T2 to detect CAD without the need for an intravenous contrast agent.99mTc-Red-Blood-Cell method [In the current study, we quantified myocardial perfusion and MBV using first-pass contrast-enhanced CMR. Several approaches have been proposed for quantifying myocardial perfusion and MBV. PET  and myocl method , 48. FurA study cohort of healthy subjects with low measurement variability may not fully elucidate the relationships between the ECV, MBV and perfusion with native T1 and native T2 at rest. Therefore, a multivariate linear regression analysis of the changes in the parameters was employed by investigating rest and stress in a combined fashion. This introduced a variability in native T1 and T2 necessary to evaluate the relevant relationships. The multivariate analysis showed that the combined changes in myocardial perfusion and ECV best explain the increase in native T1 and T2 mapping in response to adenosine stress. This is furthered supported by the finding in the univariate analysis for native T1 and native T2 at rest and stress, respectively. The analyses indicate that ECV was the main contributor to these measures, see Additional file In the current study the MOLLI 5s(3s)3s sequence was used due to the clinical routine at the time of the study. MOLLI sequences can be heart rate dependent due to two major factors; the time between inversion, and the SSFP readout influence on each inversion recovery. By setting the time between inversions in seconds instead of heart beats as in the MOLLI 5(3)3 protocol, heart rate dependency is mitigated , howeverA recent study suggests that stress native T1 mapping can be used to differentiate between obstructive epicardial disease and microvascular disease , the mecThis study was conducted in a cohort of healthy subjects free of known cardiovascular disease, and therefore there is a need for larger scale studies to confirm the findings in older subject and patients with CAD. Furthermore, some of the subjecs had a high level of fitness, which is reflected in the slightly higher LV volumes and slightly lower LV ejection fraction, which is in agreement with previously published values in athletes . The finThe T2 mapping technique used in this work was based on a T2 prepared sequence, which may introduce heart rate sensitivity, off-resonance, and T1 dependencies in the quantification.Myocardial native T1, native T2, perfusion, MBV, and ECV all increase during adenosine stress in healthy subjects. Changes in myocardial native T1 and T2 during adenosine stress in normal physiology can largely be explained by the combined changes in myocardial perfusion and ECV.Additional file 1. Reproducibility, segmental values and respective linear regression. Data include tables on intra- and interobserver variability, segmental values of the respetive maps, and linear regression at rest alone and stress alone.


A 12-lead ECG is a simple and less costly measure to assess cardiac amyloidosis and may reflect the infiltrative nature of cardiac amyloidosis and have prognostic value for predicting overall survival in patients with cardiac AL amyloidosis. Therefore, we investigated the associations of surface ECG parameters with left ventricular (LV) global longitudinal strain (GLS) and prognosis in patients with cardiac AL amyloidosis. We performed a multi-center, retrospective analysis of 102 biopsy-proven cardiac AL amyloidosis patients. Baseline studies included 12-lead surface ECG and echocardiography, with two-dimensional strain analysis performed within one month of diagnosis. From the Kaplan-Meier survival analysis, patients with prolonged QTc (≥483 msec) had significantly poorer survival. ECG scores were assigned according to presence of prolonged QTc (≥483 msec) and abnormal QRS axis, and the study participants were divided into three groups according to ECG score. Mean absolute value of LV GLS and regional LV longitudinal strain (LS) differed significantly among the three groups and decreased in a stepwise manner as ECG score increased. Log NT-proBNP increased in a stepwise manner as ECG score increased. Prolonged QTc (≥483 msec) and abnormal QRS axis showed significant incremental values in addition to the revised Mayo stage. The presence of prolonged QTc (≥483 msec) and abnormal QRS axis showed significant incremental values for overall mortality rates. In addition, ECG scores consisting of presence of prolonged QTc (≥483 msec), and abnormal QRS axis showed good association with longitudinal LV dysfunction and NT-proBNP. ECG finding may provide prognostic additional information regarding prognosis of AL amyloidosis with cardiac involvement. Therefore, assessing cardiac burden of amyloidosis is important for prognosis and future treatment strategy. Previous studies suggested that left ventricular (LV) global longitudinal strain (GLS), measured from two dimensional echocardiography with strain analysis has prognostic value in patients with AL amyloidosis and correlate with amyloid burdens4.Primary light-chain (AL) amyloidosis is a plasma cell disorder marked by the deposition of immunoglobulin-derived amyloid in multiple organs, including the heart. Cardiac involvement is characterized by infiltrative cardiomyopathy, and it is the major determinant of overall survival in light-chain (AL) amyloidosis patients. Feasibility of intensive treatment and quality of life are often affected by cardiac involvementA 12-lead ECG is a simple and less costly measure to assess cardiac amyloidosis. We hypothesized that the features of a surface 12-lead ECG would reflect the infiltrative nature of cardiac amyloidosis and have prognostic value for predicting overall survival in patients with cardiac AL amyloidosis. Therefore, we investigated the features of surface ECG for association with prognosis for overall survival in cardiac AL amyloidosis. Also, we explored association of ECG parameters with LV GLS and regional longitudinal strains (LS).During the median follow-up of 23 months, a total of 43 patients died. The mean age of all study participants was 61.6 years, and 63% were men. At baseline, a total of 48 patients (47%) were classified as revised Mayo Stage IV, and all other patients were at Stage III  or abnormal QRS axis (ECG scores). The patients were classified into three groups according to ECG scores: patients with neither prolonged QTc (≥483 msec) nor abnormal QRS axis , patients with either prolonged QTc (≥483 msec) or abnormal QRS axis , and patients with both prolonged QTc (≥483 msec) and abnormal QRS axis . The mean values of LV GLS, basal LV LS, and apical LV LS differed significantly among the three groups Fig. , and theProlonged QTc (≥483 msec) and abnormal QRS axis showed significant incremental values for overall survival in addition to revised Mayo stage  Prolonged QTc (≥483 msec) and abnormal QRS axis showed significant incremental prognostic values in addition to revised Mayo stage; (2) ECG scores which were assigned by presence of prolonged QTc (≥483 msec) and abnormal QRS axis, showed good associations with the mean absolute values of LV GLS and regional LS; and (3) mean values of Log NT-proBNP differed significantly according to ECG score and showed an increasing trend as ECG score increased.6. However, only a few studies have investigated the prognostic values of surface ECG parameters in the setting of biopsy-proven cardiac amyloidosis. In this study, we hypothesized that surface ECG may reflect the amyloid burden in cardiac AL amyloidosis and, therefore, may associate with LV GLS and prognosis.The ECG is a simple and low cost diagnostic evaluation. The diagnostic value of surface ECG for cardiac amyloidosis is well known7. However, they were not associated with overall survival or LV GLS. A previous study by Cyrille et al.8 suggested that low voltage QRS, defined as Sokolow index ≤1.5 mV, was independently associated with adverse outcomes in cardiac amyloidosis8. In our study, neither Sokolow index ≤1.5 mV nor low voltage QRS  was associated with overall survival. This difference may result from different study populations. The study by Cyrille et al.8 included both AL and transthyretin amyloidosis, which have different prognoses and disease profiles1. In addition, they included patients with image-based diagnosis of cardiac involvement if the histological documentation of Congo red staining was positive from other organs, which could have missed early involvement of cardiac amyloidosis. As they mentioned in their study, low voltage pattern could be less prevalent in early stages of cardiac amyloidosis. In our study, we included only patients with cardiac AL amyloidosis confirmed by endocardial biopsy, a confirmatory diagnostic method, and there were some patients with equivocal echocardiographic findings even with positive endocardial biopsy. Previous studies have suggested that the presence of pseudoinfarction and fragmented QRS is associated with prognosis in cardiac AL amyloidosis defined by either endomyocardial biopsy or echocardiographic evidence in systemic amyloidosis10. However, neither pseudoinfarction nor fragmented QRS showed prognostic value in our study.Similar to previous studies, the present investigation showed that low voltage in limb leads (59%), poor R progression (53%), and pseudoinfarction (47%) were the most common findings15. From our results, prolonged QTc interval remained independently associated with overall mortality, even after adjusting for revised Mayo stage, LV GLS, and other variables. In addition, the QTc interval showed a modest correlation with log NT-proBNP  , suggesting an association between LV longitudinal mechanical dysfunction and electrocardiographic repolarization abnormality  and abnormal QRS axis showed significant incremental value for overall mortality rate in AL amyloidosis patients with cardiac involvement. ECG scores consist of presence of prolonged QTc (≥483 msec), and abnormal QRS axis showed good association with longitudinal LV dysfunction and cardiac biomarker, NT-proBNP. Surface ECG findings may provide prognostic additional information regarding prognosis of AL amyloidosis with cardiac involvement.We retrospectively reviewed the medical records of patients who were diagnosed with systemic amyloidosis from January 2009 to December 2016, at Seoul National University Hospital and Samsung Medical Center. All patients had biopsy-proven amyloidosis confirmed by Congo red staining and immunohistochemistry of any tissue specimen. Cardiac involvement was confirmed by endomyocardial biopsy, and these patients were included in the study. Any patient with poor echocardiographic images, no follow-up information, persistent atrial fibrillation, paced rhythm, or previous history of myocardial infarction was excluded. In total, 102 patients with cardiac AL amyloidosis were analyzed .The baseline clinical information, laboratory results from blood samples, 12-lead electrocardiography (ECG), and two-dimensional transthoracic echocardiography at the time of diagnosis were reviewed. The Modification of Diet in Renal Disease (MDRD) equation was used to calculate estimated glomerular filtration rate (eGFR).th, 2017) for all other patients. Date of baseline was within one month of diagnosis. Occurrence and date of death and ongoing survival status were routinely monitored by regular visits or telephone calls. The median follow-up duration of the censored cases was 23.0 ± 26.5 months.The mortality endpoint was defined as the time to all-cause death from baseline for all deceased patients and time to censor date , and pseudo-infarct pattern . QRS voltage amplitude was measured as the sum of the S wave in V1 and the R wave in V5 or V6 and presented as the Sokolow index8. LV hypertrophy was defined by the Sokolow-Lyon’s criteria19 (S wave in V1 and R wave in V5 or V6 ≥ 3.5 mV) and by the Cornell criteria (R wave in aVL and S wave in V3 > 2.8 mV in men or >2 mV in women or R wave in aVL > 1.2 mV)20. Patients with left bundle branch block on electrocardiogram were excluded from the analysis of left ventricular hypertrophy and pseudoinfarct8. Poor R progression was determined if the R wave in V3 was ≤3 mm. Fragmented QRS was defined by the presence of various RSR’ patterns with or without a Q wave and included an additional R wave (R), notching of the R wave, notching of the downstroke or upstroke of the S wave, and the presence of >1 R′ in two contiguous leads corresponding to a major coronary artery territory9. Normal QRS axis was defined as ≥−30° and <90°. The QRS, QT, QT corrected interval (QTc), and PR interval were measured in all patients.The baseline 12-lead ECG was analyzed for the following characteristics: rhythm, prolonged PR (>200 msec) interval, low voltage (defined by amplitude of QRS in each limb lead ≤0.5 mV21. Left ventricular (LV) end diastolic dimension, end systolic dimension, interventricular septal thickness, LV posterior wall thickness, and left atrial volume index were measured. Mean LV wall thickness was calculated by averaging the thickness of the interventricular septum and the posterior wall. The ratio of early transmitral flow to early septal mitral annular diastolic velocity (E/e’) was measured as an index of LV filling pressure.All patients underwent standard baseline echocardiography according to the previous guidelines using Vivid 7 or Vivid 9 cardiovascular ultrasound system 23.For two-dimensional strain analysis, three consecutive cardiac cycles were recorded and averaged, and the frame rates were set to 60–80 frames/sec. The analysis was performed offline using customized software . The endocardial border of the LV was manually traced from three apical views  to obtain LV GLS. In addition, regional LV longitudinal strain (LS) values were calculated by averaging six basal, six mid, and six apical segments to obtain basal, mid, and apical LV LSContinuous data were expressed as mean ± standard deviation, and categorical variables were expressed as absolute number (percent). Receiver operating characteristic (ROC) curves were used to assess the predictive accuracy of QTc on overall mortality. Differences in overall survival according to QTc or QRS axis were assessed using log-rank analysis with right censoring and displayed by Kaplan-Meier survival curves. Patients were scored according to presence of QTc ≥483 msec and abnormal QRS axis. Continuous variables were compared among the three groups using one-way ANOVA. Univariate and multivariate Cox proportional hazard analyses were conducted to evaluate associations between baseline variables  and overall survival. The incremental prognostic utility of ECG parameters was assessed by comparing the global chi-square values. All analyses were performed using SPSS version 24 . A p value < 0.05 was considered statistically significant.This study was approved by the Ethics committee of Samsung Medical Center. Informed consent was obtained from all subjects, and all methods were carried out in accordance with the relevant guidelines and regulations according to the principles expressed in the Declaration of Helsinki. All study protocols were approved by Institutional Review Board at Samsung Medical Center.supplementary tables and figures


Extracellular volume (ECV) has been validated as a surrogate measure of interstitial fibrosis, that is increased in both hypertension-induced left ventricular hypertrophy (H-LVH) and hypertrophic cardiomyopathy (HCM). We aimed to explore the correlation between ECV and left ventricular cardiac function. Eighty-one patients with HCM, 44 with H-LVH and 35 controls were prospectively enrolled. Even among patients with normal diastolic function, patients in HCM group had increased- ECV. In terms of diastolic dysfunction (DD), a similar increase in ECV was associated with a larger percentage of patients with severe or moderate-to-severe DD in HCM group. In addition, there was a compensatory increase in the left ventricular ejection fraction (LVEF) in HCM, but no hyperdynamic LVEF was observed in H-LVH. ECV was negatively correlated with LVEF in the late gadolinium enhancement (+) (LGE+) subgroups in the H-LVH group, while no significant linear correlation was observed in HCM group. The increased ECV in HCM patients with normal diastolic function warrants further exploration of the prognostic value of ECV assessments in the early stages of HCM. The associations between ECV and left ventricular functional parameters differed and taking both LGE and ECV into account might be reasonable way to differentiate between the two disorders. However, the characteristics of HCM may be due to an intramural, congenital component of the underlying cardiomyopathy process2. Hypertrophic remodelling in both disorders has been documented to be associated with altered collagen synthesis and degradation and increased extracellular volume (ECV)4. Although increased ECV may be one of the mechanisms of altered cardiac function, whether the same magnitude of one increase in ECV is related to a similar degree of hypertrophy in these two disorders is unclear. More importantly, little is known about the correlation between ECV and systolic and diastolic function. The differences in the ECV that are responsible for altered systolic and diastolic function that lead to with regard to different causes of hypertrophy are not completely understood but could be important for treatment timing and treatment options in these disorders6.Although both hypertension-induced left ventricular hypertrophy (H-LVH) and hypertrophic cardiomyopathy (HCM) have common features, such as familial heredity, myocardial hypertrophy and possibly diastolic dysfunction, the extent and pattern of these hypertrophies differ, perhaps due to underlying distinct pathophysiologies. Histologically, hypertensive cardiac remodelling is the result of adaptive changes to pressure overload7. Several recent clinical studies have suggested that T1 mapping with ECV estimations will advance our understanding of the role of the extsracellular matrix in numerous pathophysiological processes of the human heart8. This technique has been especially useful in cases of homogenous “diffuse fibrosis,” such as in H-LVH9 and HCM4. Because the myocardial scarring visualized via late gadolinium enhancement (LGE) and the calculated ECV may not yield the same findings, the same degree of interstitial fibrosis in H-LVH and HCM patients may not be visualized equally on CMR. Therefore, when combining multi-modality imaging with the currently available T1 maps, ECV may provide insights into the relationships between visible and non-visible fibrosis, clinical features and pathological changes.ECV measured with cardiac magnetic resonance (CMR) imaging techniques, which use regions of interest drawn on CMR T1 maps, has been validated as a surrogate measure of interstitial fibrosis with high accuracy and reproducibilityThe goal of this study was to evaluate the relationship between ECV changes and diastolic and systolic functions in patients with H-LVH and HCM to better understand the underlying pathologies of these two cardiomyopathies.One hundred sixty-seven patients were enrolled based on the inclusion and exclusion criteria. One patient did not complete post-contrast T1 mapping due to heart failure. Two patients scored a 1 on ECV mapping (1 patient with LVH and 1 patient with HCM) and were not included due to image artefacts that precluded analysis. Three were diagnosed with infiltrative cardiomyopathy and one was confirmed to have coronary artery disease after CMR. One hundred sixty patients were separated into 3 groups .A total of 960 maps corresponding to 160 consecutively imaged patients were scored. Of 5,120 segments, 5,018 (98%) segments were able to be analysed . A Bland- Altman plot showed excellent agreement between operators for ECV, with average difference estimates of 0.002 (95% CI of 0.039) and 0.042 . The same reasonable agreement was observed for the native T1  and post-T1 measurements .–16.0) mm in the H-LVH group, p < 0.001), but the LVM and LVMI were similar between the H-LVH and HCM groups (p > 0.05). In terms of LV function, the LVEF was comparable between the H-LVH group and the control group, but it was hyper-dynamic in the HCM group . A higher LV mass/volume ratio was found in the H-LVH and HCM groups than in the control group (p < 0.001). The presence of scarring was found in only 15 of 44 (34.1%) patients with H-LVH, but it was frequently (68 of 81) found in the HCM group (84%) (p < 0.001). Visually recognizable scar sizes were much smaller in the H- LVH group (0–0.94% for the interquartile range) than in the HCM group .The patient characteristics are shown in Table Table The same LVMI values corresponded to similar ECV values . The ECV did not differ based on the type of disease but showed distinct distributions between the two diseases Fig. . Patientth percentile in the H-LVH group, 1.33–2.30 in the HCM group and 0.65–0.97 in the control group, p < 0.001; Fig. The impact of ECV on diastolic properties is shown in Tables In terms of systolic function, a hyperdynamic LVEF was observed in the HCM patients but not in patients with H-LVH  or diffuse myocardial fibrosis (ECV) and LVEF in the two diseases Fig. . The LVEThe main findings of this study are summarized here. An increased ECV was observed in patients with HCM, even in the sub-group of patients with normal diastolic function. An increased ECV was associated with a severely impaired LV mass/volume ratio and a hyperdynamic LVEF in the HCM group, but it was associated with only a mild impairment of the LV mass/volume ratio and was not associated with hyperdynamic LVEF in the H-LVH group. Taking both LGE and ECV into account might be a reasonable way to differentiate between HCM and H-LVH.10, can be noninvasivelydetermined using CMR without impacting the field strength, gadolinium clearance rate, time of measurement, injection dose, body composition, or haematocrit, which ware limitations of single native T1 or post-contrast T1 measurements11. Clinically, increases in ECV have been reported in a variety of cardiac diseases, including myocardial infarction, myocarditis, HCM and H-LVH9. From a prognostic perspective, increased ECV or scarring may be related to ventricular tachyarrhythmia12. In the current study, although the maximum end diastolic wall thickness in the HCM group was significantly thicker than that of the H- LVH group, the overall LVM and LVMI were similar between the disease groups. The ECV was also increased in both groups, which is consistent with previous publications13, but the increase was not specific to either disease and the same LVMI corresponded to a similar range of ECVs.Unlike single native T1 or post-contrast T1 measurements alone, ECV, which is a biopsy- validated surrogate measure of interstitial fibrosis3. In young patients with aortic stenosis, the myocardial ECV is significantly increased and is associated with echocardiographic indices of diastolic dysfunction. Additionally, an increased ECV arises from a reduced rate of relaxation and increased stiffness14. In our current study, we used both myocardial stiffness indices (the LV mass/volume ratio) and combined-parameter-determined diastolic grading to assess diastolic function. To our surprise, an increased ECV was observed in both cardiomyopathies (nearly 30% of each group), even in patients with normal diastolic function, which promoted us to suggest that ECV may serve as an early indicator of diastolic impairment susceptibility from a mechanical aspect. Theoretically, interstitial fibrosis occurs earlier and is followed by clinical manifestations, including myocardial stiffness or a decreased LVEF. An increased ECV was associated with a severely impaired LV mass/volume ratio and was observed in 30% of the patients with grade II-III diastolic dysfunction in the HCM group. However, in the H-LVH group, it was associated with a mild impairment of the LV mass/volume ratio and showed a much weaker relationship to moderate-to-severe diastolic impairments. The mechanisms underlying this phenomenon are at least partially due to extracellular matrix distribution. Despite similar ECV values, the distribution of the extracellular matrix was distinct between the two disorders  values in all the endocardial and epicardial myocardial layers were significantly lower in HCM subjects than in controls. However, to maintain the LVEF, the endocardial global circumferential strain (GCS) was maintained to compensate for the decrease in endocardial GLS. Therefore, the ratio of endocardial strain to epicardial strain may increase to achieve a compensatory effectTo further explore the effect of pathological progression on left ventricular function, we combined LGE and ECV to evaluate the relationship between regional or diffuse myocardial fibrosis and LVEF in these two diseases. We found that taking both LGE and ECV into account might be an option to differentiate HCM and H-LVH; howeve, this finding needs further validation in larger studies.Limitations: First, there was a large overlap in ECV between HCM and H-LVH. ECV represents the extent of fibrosis in both diseases. Therefore, ECV can neither serve as a predictor of ongoing hypertrophic progression nor provide aetiologicinformation. Second, this study was conducted with a relatively small sample size in the H-LVH group because only patients with a definite elevation in LVM were recruited. Third, the ability of ECV to quantify diffuse fibrosis can only be interpreted on a group basis (rather than on a per-patient basis) due to partial volume effects, patient motion, etc. Combining ECV images and LGE may increase diagnostic confidence because the LGE image quality is generally excellent and does not have the same artefacts. Finally, the assessment of diastolic function in this study was based on echocardiographic measurements, which may not always perfectly agree with invasive assessments.Conclusions: Distinct extracellular matrix distributions accounted for the clinical imaging manifestations of H-LVH and HCM. An increased ECV was found in patients with the cardiomyopathies with normal diastolic function. Further exploration of the prognostic value of ECV is warranted. Myocardial ECV was similarly increased in the H-LVH and HCM groups and was differentially associated with systolic and diastolic function. Taking both LGE and ECV into account might be a reasonable way to differentiate between HCM and H-LVH.Perspectives: The clinical implications of this study include the following: the future exploration of the prognostic value of the ECV; the use of ECV in HCM patients with normal diastolic function to screen for subjects with increased myocardial fibrosis and observe the clinical significance of this detection; and the increasing importance of ECV findings for pharmaceutical treatment timing and treatment options in these disorders. Second, based on the differences in systolic and diastolic manifestations between these two cardiomyopathies, more prospective studies should focus on combining systolic and diastolic functional measures with other parameters, such as wall thickness, myocardial deformation and LGE, to further contribute to differentiating between HCM and H-LVH.All participants provided written informed consent and the protocol was approved by the IRB. All experiments were performed in accordance with the current imaging guidelines and regulations. Consecutive subjects were prospectively enrolled into 3 cohorts between July 2014 and February 2016. The cohorts were as follows: an H-LVH group, an HCM group and a control group.The diagnosis of HCM was supported by left ventricular hypertrophy diagnosed on echocardiography  with either a genetic determination of a pathogenic mutation or a history of syncope with systolic anterior motion of the mitral valve, mitral regurgitation and resting left ventricular outflow tract obstruction.2 for men or >61 g/m2 in women, as defined by Olivotto et al.17.The diagnosis of LVH was based on medical history and conventional echocardiography, including long durations of uncontrolled hypertension, i.e., for at least 5 years, with a systolic blood pressure (BP) ≥150 mm Hg, diastolic BP ≥90 mm Hg, or both in the absence of other cardiac or systemic diseases and echocardiographic demonstration of a hypertrophic LV . Subjects were enrolled in the H-LVH group if their left ventricular mass (LVM) by body surface area (LVMI), as measured by cardiac magnetic resonance imaging, was >81 g/mCandidates who served as controls were used to establish baseline myocardial T1 and ECV values. The controls were generally scheduled for CMR for atypical chest pains, palpitations, or pre-operative evaluation for non-cardiac surgery and had no known hypertension, other systemic illness or family history of cardiomyopathy or sudden death. They also had normal electrocardiographic, echocardiographic, or CMR results, including a normal wall thickness and LVMI without hyperenhancement.The exclusion criteria were age <18 years old or >80 years old, documented coronary artery diseases or prior angiography for coronary artery disease (>50% stenosis), Framingham risk level ≥5% in the previous 10 years, or atrial fibrillation during echocardiography, which impedes the grading of diastolic function. Patients with known infiltrative cardiomyopathies or septal ablations for drug-refractory hypertrophic obstructive cardiomyopathy or patients with standard metallic contraindications for CMR were also excluded.18. Normal values for age-related Doppler-derived diastolic measurements for Chinese patients were adapted from the EMINCA study19.The assessment of LV diastolic function was an integral part of routine echocardiographic examinations . The mitral E/A ratio, tricuspid regurgitation velocity, mitral DT, septal E′ and lateral E′ were recorded. The left atrial volume was obtained using the apical 4-chamber and 2-chamber views. The evaluation of left ventricular diastolic function was performed based on the 2016 recommendations for the evaluation of left ventricular diastolic function from the American Society of Echocardiography and the European Association of Cardiovascular ImagingAll CMR examinations were performed using a Philips 3 T Ingenia MR system .A volumetric cavity assessment was obtained by whole-heart coverage of short-axis slices (7- mm thick with a 3-mm gap). Additionally, video images of 3 long-axis views  were acquired. All video images were acquired using a balanced, steady-state, free precession sequence combined with parallel imaging  and retrospective gating during a gentle, expiratory breath-hold .We integrated native and post-contrast myocardial T1 mapping into our routine imaging protocol to determine the ECV. A steady-state free precession, single breath-hold modified Look-Locker inversion recovery sequence  was used for T1 mapping and a “5–3–3” scheme (in seconds) was chosen to reduce respiratory motion artefacts, contractile motion blurring and black banding artefacts. The scheme was performed on an equatorial 3 end-diastolic LV short-axis slice  before and 15 min after a bolus intravenous injection of 0.15 mmol/kg of gadopentetate dimeglumine . The typical acquisition parameters were as follows: field of view, 320 × 320; TR, 2.3 ms; TE 1.06, ms; flip angle, 20°; interpolated voxel size, 2.0 × 2.0 × 8 mm; 160 phase-encoding steps; SENSE = 2; cardiac delay time, TD = 350 ms; and 1,200-ms acquisition time for a single image. The region of interest was positioned at the magnet isocenter. Shimming and centre frequency adjustments were performed to generate images free from off-resonance artefacts if necessary.LGE imaging was performed with gapless whole-heart coverage of short axis slices 10 min after the administration of a dose of 0.15 mmol/kg body weight of gadopentetate dimeglumine using a mid-diastolic inversion-prepared, 2-dimensional gradient echo sequence . Segmented LGE images with at least three matching slices and native T1 images were also acquired.21.Routine CMR analysis was performed using commercially available software . The CMR data analysis was performed by 2 observers who had experience with CMR and who were blinded to the clinical information. Systolic function was represented by the left ventricular ejection fraction (LVEF). Because the LV mass/volume ratio is closely related to the LV flow propagation velocity and early intraventricular pressure gradient, the LV mass/volume ratio was adopted as a measure of LV stiffness with a normal range from 1–1.5For LV volume and mass, endocardial LV borders were manually traced at end-diastole and end-systole. The papillary muscles were included as part of the LV cavity volume. LV end-diastolic and end-systolic volumes were determined using Simpson’s rule. All volumetric indices were normalized to the body surface area.42 Version 5.5.6.1, Alberta, Canada).The LGE images were examined for the presence and extent of regional fibrosis of the LV Reported T1 values were derived with the operator blinded to the LGE image groups. In addition to the T1 values of the myocardium and blood pool, we calculated the ECV according to the formula: ECV = λ * (1 − haematocrit), where λ = [ΔR1 myocardium]/[ΔR1 blood pool] before and after gadolinium contrast injection (where R1 = 1/T1). Haematocrit was tested on the same day in all subjects.22. T1 maps were then scored for overall quality based on a 5-point scale23. Briefly, a score of 1 (non-diagnostic) indicated that the T1 value could not be reliably measured anywhere in the myocardium and the patient was then excluded from the current study. Score of 2, 3, 4 and 5 indicated poor, fair, good and excellent performance, respectively, providing the ability to distinguish regions of normal myocardium from noise or artefacts.The “5-3-3” scheme (in seconds) from MOLLI 5.1 is independent of heart rate and already compensated for respiratory motion artefacts, contractile motion blurring and black banding artefacts. The position of the source images was initially manually adjusted using MRmap to correct for potential mis-registration caused by translational displacement in cases of poor breathholdingMoreover, a second blinded operator analysed more than 50% of the cases, which were randomly selected. The same analytic technique was used and the results were compared using the Bland-Altman method.Quantitative data are presented as the mean ± SD or the median (interquartile range). Categorical data are presented as numbers and percentages. All quantitative data were assessed for normality using the Kolmogorov-Smirnov test and comparisons among the 3 groups were performed with nonparametric Kruskal-Wallis and Dunnett’s tests. For the qualitative data, comparisons of the three groups were performed using Pearson’s chi-squared test or Fisher’s exact test. Inter-observer reproducibility of T1 mapping and ECV measurements were assessed using the Bland- Altman method and an intra-class coefficient analysis. All analyses were performed using IBM SPSS Statistics software, version 17.0  Two-tailed p-values < 0.05 were considered significant.The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.Supporting data are available to editorial board members and referees.The IRB of Renji Hospital approved the protocol.All participants provided written informed consent.


A 76-year-old male with a small bowel neuroendocrine tumor with hepatic metastases presented with new onset lower extremity swelling, bloating, and weight gain which ultimately lead to cardiac magnetic resonance (CMR) to evaluate for cardiac involvement of disease. CMR showed right and left ventricular myocardial metastases along with findings suggestive of carcinoid heart disease. The patient had severe tricuspid valve regurgitation necessitating surgical valve repair. The patient underwent bioprosthetic tricuspid valve replacement and debulking of the metastases with surgical pathology confirming neuroendocrine tumor metastases. Follow-up clinical evaluations at 3, 6, and 9 months postoperatively showed improvement in cardiac function and stable hepatic tumor burden. This case demonstrates the utility of CMR to diagnose myocardial metastases and carcinoid heart disease complicated by severe tricuspid regurgitation, which guided surgical management. Neuroendocrine tumors (NETs) are a diverse group of tumors arising from neuroendocrine cells, and they can cause primary tumors in many different organs including the lungs, small intestine, rectum, pancreas, and other organs . Within NETs of the midgut  commonly release vasoactive substances including 5-hydroxytryptamine (serotonin), histamine, tachykinins, and prostaglandins . When thIn rare cases, NETs can metastasize to the heart , 11. CarA 76-year-old male with stage IV, small bowel NET metastatic to the liver had been followed by our institution for 4 years with stable hepatic metastatic disease on octreotide long-acting release (LAR) therapy. Originally, the tumor Ki-67 index was 5% and 24-hour urine 5-hydroxyindole acetic acid (5-HIAA) was 105 mg. The patient presented with mild progression of disease on abdominal magnetic resonance imaging (MRI)  after apCMR  showed aThe patient underwent bioprosthetic tricuspid valve replacement and biopsy and debulking of the myocardial tumors. The myocardial tumors were histologically confirmed as NET metastases. The patient recovered well from surgery, and follow-up clinical visits demonstrated significant improvement in his carcinoid heart disease. As of the latest visit, the patient has excellent cardiac function with resolution of tricuspid regurgitation. His 9-month postoperative follow-up CT scan showed relatively stable disease, and his urine 5-HIAA was improving. The patient is continuing on octreotide LAR 30 mg.We present a unique case of carcinoid heart disease and myocardial metastases both contributing to this patient's severe symptomatic tricuspid regurgitation. The tricuspid valve thickening is a specific finding of carcinoid heart disease, and well-defined lesions with arterial perfusion in the RV and LV walls are specific for metastases. Previous authors have suggested that vasoactive mediators associated with myocardial metastases may accelerate the onset of carcinoid heart disease, which could explain the case described here , 16.Carcinoid heart disease manifests via the accumulation of carcinoid plaque composed of smooth muscle, myofibroblasts, and elastic tissue . Plaque Echocardiography serves as first line screening for cardiac involvement in patients with carcinoid syndrome. Common echocardiographic features of carcinoid heart disease include morphologic changes to the tricuspid valve causing a thick retracted appearance with decreased mobility and enlargement of the right atrium and ventricle related to valvular insufficiency . SurgicaCMR offers more specific evaluation of cardiac lesions to help differentiate benign lesions from metastases compared to echocardiography evaluation which is based on lesion intrinsic signal and perfusion characteristics . While eThis case demonstrates the importance of CMR to evaluate for carcinoid heart disease and cardiac metastases. The results of the CMR exam in our case lead to characterization of myocardial metastases and allowed for planning of metastasis resection during the tricuspid valve bioprosthetic surgery. The case also serves as a reminder for providers that while echocardiography may offer first line screening for cardiac involvement when carcinoid heart disease is suspected, CMR may be useful when myocardial metastases are suspected for potential surgical planning.