Objective: This study aimed to quantitatively assess myocardial strain in preterm children aged 5 to 8 years of pregnancy complicated by severe preeclampsia (PE) by two-dimensional (2D) speckle tracking echocardiography.Method: A cohort study of 23 preterm children delivered by severe PE pregnant women from 2010 to 2012 in the First Affiliated Hospital of Soochow University was carried out. 23 preterm children from uneventful pregnancies in the same period served as controls. Myocardial functions including left ventricular longitudinal strain, radial strain, circumferential strain, and right ventricular longitudinal strain were evaluated by conventional Doppler, tissue Doppler imaging, and 2D speckle-tracking echocardiography (2D STE). All examinations were performed by an experienced ultrasonographer using the VIVID E9  machine, according to standard techniques.Results: Children aged 5–8 years delivered from severe PE presented less weight , shorter height  and faster heart rates  compared to offspring of normotensive women. There were no significant differences in global left ventricular longitudinal strain, radial strain, circumferential strain, and right ventricular longitudinal strain between the children in the experimental group and the control group (P > 0.05).Conclusion: Exposure to the intrauterine environment of severe PE during the fetal period did not have a significant impact on cardiac structure in premature children at 5–8 years old, but they had a higher resting heart rate which may be associated with cardiovascular disease in the long run. Preeclampsia is a common complication during pregnancy. There is evidence that preeclampsia (PE) could cause epigenetic alterations, among which alterations in imprinted genes could affect the process of embryo formation, trophoblastic growth, embryonic and organismal development . AlteratThe current studies on the effects of preeclampsia on myocardial function in offspring are inconsistent. Some researchers believe that the damaged cardiac structures gradually recover as the offspring grow and develop. A longitudinal cohort study consisting of 784 Finnish adults (34–49 years) found that slight changes of cardiac structure in adults born small for gestational age (SGA) were unlikely to have pathologic effects on cardiovascular disease . HoweverThe two-dimensional (2D) ultrasound image of the heart is composed of many acoustic spots evenly distributed in the myocardium, which move synchronously with the myocardial tissue. The speckle tracking imaging can continuously track the trajectory of each spot and quantitatively analyze movement speed and strain of the myocardial tissue, which can accurately reflect myocardial function. In the current study, we performed 2D-STD to evaluate cardiac structure and function to explore whether exposure to the intrauterine environment of severe PE during the fetal period caused cardiovascular disease risk in premature children at 5–8 years old and provide a basis for cardiac screening in children.The study included 23 preterm children delivered by severe PE pregnant women and 23 age-matched children from uneventful pregnancies from the First Affiliated Hospital of Soochow University.∗109/L); ➂ impaired liver function ; ➃ renal insufficiency ; ➄ pulmonary edema; ➅ new onset of cerebral or visual disturbances. Patients were excluded if pregnancies were complicated with diseases that may affect the development of fetal heart, such as gestational diabetes mellitus, maternal hematologic diseases, immune system diseases, malignant tumors, heart disease, intrauterine infections, fetal congenital heart disease, or other deformities.Severe preeclampsia was diagnosed according to the 2013 edition of the American College of Obstetricians and Gynecologists (ACOG) guidelines when at least one of the following was met: ➀ systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 110 mmHg (on two occasions at least 4 h apart while the patient is on bed rest); ➁ thrombocytopenia  2–4 MHz transducer. The patient was examined in the left lateral decubitus position and connected to ECG using a Vivid E9 ultrasound scanner with phased array transducers M5S-D. We acquired a 2D datum from the parasternal long-axis and short-axis views and three standard apical views and captured three consecutive cardiac cycles for each view. Pulsed Doppler images were acquired in the apical four-chamber view with the sample volume placed in the orifice of the right upper pulmonary vein and the mitral valve inflow at the leaflet tip. The cross-valve pressure difference was measured in continuous Doppler mode. Tissue-Doppler Images (TDI) analysis was performed to record mitral annulus velocities at septal and lateral walls in the apical four-chamber view.According to the recommendations of the American Society of Echocardiography, aortic root diameter left atrial diameter, interventricular septum, LVES D, and LVED D were measured from M-mode echocardiograms. The peak early (E) and late (A) trans-mitral flow velocities, the ratio of early-to-late peak velocities (E/A), and mitral flow deceleration time (DT) were measured from the mitral Doppler flow waveform. Pulsed-wave Doppler velocities of the pulmonary venous flow were obtained to analyze pulmonary vein inflow for peak velocity of systolic (S), diastolic (D), and atrial reversal waves (Ar). TDI was used to measure annular systolic velocity (Sa), early diastolic (Ea), and late diastolic (Aa) velocity at septal and lateral walls. Pulmonary artery systolic pressure (PASP) was calculated as follows: SPAP = tricuspid transvalvular pressure difference + right atrial estimated pressure . The triDatum of speckle tracking was analyzed offline using dedicated automated software EchoPAC PC, Version 113 . The myocardial region of interest (ROI) of the left ventricular was defined by the endocardial border. For the 2D longitudinal speckle tracking analysis, three ROIs were placed in an end-diastolic frame from the apical three-, four-, and two-chamber views, respectively. If necessary, the width of the ROI can be adjusted manually to exclude the pericardium.Peak systolic longitudinal strain (LS) was analyzed from apical views in all 17-left ventricular (LV) longitudinal segments and averaged to LV global longitudinal strain. Longitudinal strains of the right ventricle (RV) in all six segments of the right ventricular free wall and septum or three segments of right ventricular free wall were analyzed from the apical four-chamber view and were averaged into RV global longitudinal strain. Circumferential strain (CS) and radial strain (RS) were assessed in the parasternal short-axis views at the level of the mitral valve, papillary muscle, and apical view, and the left ventricular torsion and torque were calculated.t-test was conducted to compare differences in means. Likewise, the log-rank test was used for comparing variables with non-normal distribution. Data are presented as mean and SD or median (interquartile range). P < 0.05 was considered significant.The values of left and right ventricular LS and left ventricular torsion were transformed into z-scores normalized to body surface area and adjusted for heteroscedasticity presented by P < 0.05), shorter height  and faster heart rates . There were no differences in other conventional echocardiography values  between the children in the severe PE group and the control group. Children delivered from severe PE presented less weight , shorter height  and faster heart rates . We believed that growth retardation of premature children is induced by placental insufficiency secondary to severe preeclampsia. The results of this study are in line with a previous study in male children exposed to severe preeclampsia, suggesting 1 kg lighter and 3 cm shorter than normal children at 2 years old and a.1 kg/m2 lower body mass index at 12 years old  is a novel index that can be used to evaluate the cardiac function of various heart diseases comprehensively and is independent of the geometry of the ventricles, the quality of 2D images, blood pressure, and heart rate. The higher the MPI value, the worse the heart function. Although some studies reported higher MPI values in the offspring exposed to the intrauterine environment of severe PE compared to non-exposed during the fetal period  and withThis study has some strengths and limitations worth commenting on. There were no differences in the age, gestational week of birth, or parental characteristics  between the children in the experimental group and the control group. Pregnancies with diseases that may affect the development of fetal heart, such as gestational diabetes mellitus, maternal hematologic diseases, immune system diseases, malignant tumors, heart disease, intrauterine infections, fetal congenital heart disease, or other deformities, are excluded to minimize the impact of confounding factors. But we acknowledge that PE could increase the incidence of congenital heart disease, fetal malformations, and even death. Our exclusion made us inclined to select patients less affected by preeclampsia for this research. In addition, our study was conducted on preterm children from only one medical center which might impact the variables analyzed.In conclusion, this study demonstrated that exposure to severe preeclampsia during pregnancy did not have a significant impact on the clinical cardiac systolic and diastolic function of offspring at 5–8 years old. However, their faster resting heart rate may have suggested a negative impact on the heart and could be a potential indicator of an increased risk of cardiovascular disease in the future.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by Ethics Committee of The First Affiliated Hospital of Soochow University. Written informed consent was obtained from the individual(s), and minor(s)’ legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.BH and BZ: conceptualization. HC, YG, and FS: data curation and writing—original draft preparation. BZ: echocardiographic image acquisition. BH, JF, and XG: supervision. All authors have read and agreed to the published version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Surgical neuromodulation therapies are still considered a last resort when standard therapies have failed for patients with progressive heart failure (HF). Although a number of experimental studies have provided robust evidence of its effectiveness, the lack of strong clinical evidence discourages practitioners. Thoracic unilateral sympathectomy has been extensively studied and has failed to show significant clinical improvement in HF patients. Most recently, bilateral sympathectomy effect was associated with a high degree of success in HF models, opening the perspective to be investigated in randomized controlled clinical trials. In addition, a series of clinical trials showed that bilateral sympathectomy was associated with a decreased risk of sudden death, which is an important outcome in patients with HF. These aspects indicates that bilateral sympathectomy could be an important alternative in the treatment of HF wherein pharmacological treatment barely reaches the target dose. Heart failure (HF) affects approximately 2% of the adult population in developed countries. This number increases to 10% among people over the age of 70 years . AlthougHF patients have been treated with a combination of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II receptor blocker (ARB) if ACEI is not tolerated, a β-blocker (BB), and a mineralocorticoid receptor antagonist (MRA) . Most reEven though clinical treatment guidelines support the combined therapy based on large randomized controlled trials, medication use and dosage in clinical practice are suboptimal. In the United States, the CHAMP-HF registry presented significant gaps in the use and dose of the current medical treatment for HF. Among patients eligible for the combined therapy, 26.6%, 33%, and 76.6% did not receive ACEI/ARB/ARNI, BB, and MRA, respectively. Additionally, less than 30% of the patients received the target doses of BB and ACEI/ARB/ARNI. Only 1% of the patients received optimal treatment (ACEI/ARB/ARNI+BB+MRA) and target dosage , i.e., patients with left ventricular ejection fraction (LVEF) lower than 40%, and HF with preserved ejection fraction (HFpEF), i.e., patients with LVEF higher than 50%. A more recent classification, HF with midrange ejection fraction (HFmrEF) englobes those with LVEF between 41 to 49%. On this review, we will be focusing on HFrEF, once the development of this HF is directly linked to compensatory mechanisms that aim to improve cardiac function. HFrEF is mainly caused by ischemic heart disease, dilated cardiomyopathies of different etiologies or right heart failure secondary to pulmonary arterial hypertension. As for the main compensatory mechanisms, there are the neurohormonal systems (SNS and RAAS), Frank Starling mechanism (stretch-induced increase of preload) and myocardial structural changes (hypertrophy and hyperplasia) . An elevation in the left ventricular (LV) filling pressure causes an increase in pulmonary venous pressure ,24. The With increasing stiffness of the heart, cardiac systolic function decreases even further. Eventually, the compensatory mechanisms are overwhelmed and unable to sustain cardiac function without further decompensation. The neurohormonal system is the main target for the treatment of HFrEF to dampen this vicious cycle -12.The ACEI/ARB/ARNI and MRA target the RAAS, while the SNS is directly targeted by the BB -7. AntiRenal denervation (RD) has been studied using various experimental models and clinical trials. RD is based on dampening renal sympathetic activity, which is responsible for increasing sodium and fluid retention and activating the RAAS. In experimental models of myocardial infarction in rats, RD was associated with less fibrosis and cardiac remodeling, better cardiac function, decreased SNS activation, and improved hemodynamics ,33. In tAnother important point to discuss is whether reinnervation occurs after RD. Using a sheep model, Booth et al. showed that 5 months after the RD procedure, almost complete functional and anatomical reinnervation occurred. Eleven months later, no differences were found in RD and non-RD animals, in relation to the renal distribution of afferent and efferent nerves and renal NE levels . There iVagal nerve stimulation (VNS) is another therapy option, which is based on the aforementioned disbalance between the SNS and the parasympathetic nervous system in HFrEF. Rather than attempting on or dampen SNS activation, VNS tries to balance the autonomic nervous system by stimulating the vagal nerve with an implanted device. In experimental studies using rat models of HFrEF, VNS baroreflex activation decreased cardiac oxygen consumption, inflammation, SNS activity, and overall mortality -38. In The success of VNS in experimental models has not been replicated in clinical trials. In the randomized, sham-controlled, double-blind NECTAR-HF trial, VNS did not improve LV remodeling for 6 months, nor did it achieve any of the secondary efficacy endpoints . INOVATEPulmonary artery denervation (PADN) is an alternative option for primary pulmonary arterial hypertension (PAH) in an attempt to prevent HFrEF development. The PADN mechanism is based on the removal of sympathetic nerves from the main pulmonary artery trunk, thereby inhibiting excessive activation of the SNS. An experimental model of PH showed improved hemodynamics and diminished pulmonary artery remodeling . In patiThoracic sympathectomy was first described as an alternative for arrhythmia control in patients with angina and ventricular arrhythmia . ThoraciAlthough LS has positive results in controlling arrhythmias, nervous plasticity of the stellate ganglion was observed after LS treatment. Unilateral sympathectomy causes hypertrophy of the contralateral ganglion ,48. ThisOne of the main concerns about performing BS rather than unilateral sympathectomy was the maintenance of a minimal adrenergic tonus in a patient with HFrEF. A clinical trial verified the safety of BS in patients with ventricular tachyarrhythmia . AnotherThe potential benefits of LS were assessed in 10 patients with dilated cardiomyopathy (DCM) and NYHA II or III with reduced LVEF. On a short follow-up of 6 months, LS improved the LVEF, exercise performance, and quality of life. These results showed that LS is feasible; however, a larger study is required to assess its long-term effects ,53.Recently, BS was performed in a patient with nonischemic DCM, NYHA class IV, and 15% LVEF. After 1 year, the patient had no ICD shock, improved LVEF to 25%, and was removed from the transplant list, showing the potential benefit of BS in a HFrEF patient . In anotAlthough clinical trials are lacking, experimental studies in different DCM models are being published. Zanoni compared the effect of LS to BS as a treatment for myocardial infarction in rats. BS effectively controlled the overactive SNS, preventing LV remodeling and decay of function. In contrast, LS-treated rats showed a loss of wall thickness, increased fibrosis, and decreased heart function. The potential mechanism by which BS acts on ventricular remodeling is by decreasing myocardial apoptosis. BS-treated rats had diminished expression of apoptosis proteins, as LS and untreated rats had increased expression of these proteins. In addition, BS decreased the expression of matrix metalloproteinases, which are known to play a role in myocardial remodeling .Once BS was shown to be superior to LS, BS was tested in a DCM model induced by doxorubicin . DCM ratIn another unpublished experimental study using a PAH model, BS effects were evaluated in both lung microcirculation and in the RV (Unpublished data). BS was successful in preventing lung arterial wall hypertrophy, which is the primary pathological alteration observed in PAH. An interesting finding was the diminished expression of α-smooth muscle actin (α-SMA) by BS, since the augmented expression of this particular protein is associated with endothelial dysfunction and vascular remodeling. BS protected the RV from dilation and hypertrophy by decreasing pulmonary vascular resistance. Consequently, RV function was preserved under steady-state conditions and responsive to preload changes. In untreated PAH, cardiomyocyte hypertrophy was associated with mitochondrial stress, decreased mitochondrial copy number, and increased oxidative stress. BS could decrease mitochondrial stress by enhancing radical scavenging activity and mitigating oxidative stress. These results could indicate a new mechanism by which BS halts the vicious cycle of SNS-induced lesions by protecting the heart from further damage and might contribute to reverse remodeling (Unpublished data).In both the myocardial infarction and PAH models, the main cause of cardiac dysfunction was derived from an overactivated SNS in response to a lesion. In contrast, the doxorubicin model caused direct injury to cardiomyocytes. This direct injury leads to cardiomyocyte death and replacement of fibrotic tissue. It is important to highlight the success of BS in all three models, even in a direct lesion model. These results support the hypothesis that BS has a protective role in myocardial apoptosis through an unknown pathway. This mechanism might be key in preventing LV remodeling and halting the progression of HFrEF. The doxorubicin model showed that this mechanism might be different from that of ACEI and could be synergistic.Thoracic BS is a minimally invasive and promising procedure for patients with HFrEF ,54. ExpeThe current pharmacological treatment does not prevent the progression of HFrEF, as its dosage is mostly suboptimal in patients . In addiAll the authors were responsible for the manuscript drafting, editing and review.


A LV GLS value of −15.9% predicted LGE RV score > 8 (AUC 0.754 (p = 0.02)). Neither RV GLS nor biomarker levels were correlated with the extent of RV fibrosis. A cut-off value for NTproBNP of 145.25 pg/mL predicted LGE RV score > 8 points ). A cut-off value for Gal-3 of 7.42 ng/mL predicted PR Fraction > 20% . Conclusions: A significant extent of RV fibrosis was mainly detected at surgical sites of RV, affecting RV performance. CMR-FT reveals subtle LV dysfunction in rToF patients, due to decreased performance of the fibrotic RV. Impaired LV function and elevated NTproBNP in rToF reflect a dysfunctional fibrotic RV.Background: We sought to assess the interplay between right ventricle (RV) fibrosis, biventricular dysfunction based on global longitudinal strain (GLS) analysis, and biomarkers such as Galectin-3 , procollagen type III (PCIII), and NTproBNP. Methods: We studied 35 adult patients with rToF. All patients underwent a cardiac magnetic resonance (CMR) scan including feature tracking for deformation imaging. Blood biomarkers were measured. Results: LGE RV was detected in all patients, mainly at surgical sites. Patients with the highest RV LGE scoring had greater RV dilatation and dysfunction whereas left ventricular (LV) function was preserved. LV GLS correlated with RV total fibrosis score ( The improvement in the management of Tetralogy of Fallot (ToF) has led to the extended survival of adult patients with repaired ToF (rToF) ,3,4,5,6,Furthermore, imaging modalities may add valuable data to risk stratification. Cardiovascular magnetic resonance (CMR) is the gold standard technique for accurate and reproducible noninvasive measurements of biventricular size and function, quantification of valvular regurgitation, and the detection of myocardial fibrosis ,10,11. ATherefore, we aimed to assess the following: 1. Detection and distribution of right ventricle (RV) fibrosis and correlations with clinical data; 2. The prognostic role of biomarkers levels in the study population; 3. Analysis of global CMR-FT strain parameters of RV and left ventricle (LV) and their correlation with extent of RV fibrosis and biomarker levels.The study was conducted at the Adult Congenital Heart Disease Clinic, First Cardiology Department, AHEPA University Hospital, Thessaloniki, Greece. The study protocol was approved by the Institutional Review Board (1/8 January 2012) and all participants provided written informed consent.We studied 35 consecutive adult patients  with repaired ToF. Patients with a permanent pacemaker/implantable cardioverter defibrillator (ICD) were excluded, due to contraindication for CMR. All patients had a complete cardiac examination, including past medical history, physical examination, and standard 12-lead ECG, and underwent a CMR study . Standard 12-lead ECGs were acquired of all patients and the QRS duration was measured manually ,16,17. TSerum was isolated after centrifugation at 4000 rpm for 10 min at 4 °C. Galectin-3  serum levels were determined using an enzyme-linked immunoabsorbent assay (ELISA) kit . The inter-assay and intra-assay variation are 8.1% and 6.63%, respectively. Galectin values are expressed in ng/mL. Procollagen type III (PCIII) serum levels were determined using a sandwich ELISA kit . The inter-assay and intra assay variation are both <10%. PCIII values are expressed in ng/mL. NT-proBNP serum levels were determined on a COBAS 8000 immunoassay analyzer  with electrochemiluminescence immunoassay (ECLIA), using monoclonal antibodies which recognize epitopes located in the N-terminal part (1–76) of proBNP (1–108). The inter-assay and intra-assay variation are 1.5% and 2.5%, respectively.®, Bayer Inc. 2920 Matheson Boulevard East Mississauga, Bayer Healthcare, L4W 5R6 Ontario Canada).CMR imaging was performed with a Siemens Avanto 1.5T MRI scanner, using a body surface coil and a standard imaging protocol, which included ECG-gated steady-state, free-precession cine CMR acquisitions in long-axis and contiguous short-axis cine imaging. CMR variables included RV and LV end-diastolic volume index (EDVi); RV and LV end-systolic volume index (ESVi); RV and LV ejection fraction (EF); RV and LV mass index. The RV free wall below the pulmonary valve was included in the RV mass calculation while trabecular bands on the RV side of the septum were included in blood pool measurements. Pulmonary regurgitation (PR) was estimated with CMR pulmonary artery regurgitant fraction (RF). PR was graded as mild if the RF on CMR was less than 20%, moderate if it was between 20% and 40%, and severe if it was greater than 40%. All measurements were made by an experienced observer, blinded to patient clinical status. Late gadolinium imaging was performed by the same observer with the use of a two-dimensional-segmented phase-sensitive inversion recovery sequence (PSIR), and acquisition optimization for imaging nonischemic myocardial fibrosis, 10 min after intravenous administration of 0.1 mmol/kg of gadobutrol  or median (quartile 1–quartile 3). Continuous variables were analyzed by either 2-sample independent t test or Mann–Whitney test as appropriate. Correlations were assessed by Spearman rank correlation coefficient. Categorical data were analyzed by χ2 test. A nonparametric Kruskal–Wallis test was used to compare different variables in the lower, middle, and upper quartiles of the RV LGE score. Interclass correlation coefficient was used to assess the reproducibility of the RV LGE score. A probability value less than 0.05 was considered statistically significant. The prognostic potential of LV GLS by FT-CMR and biochemical markers Gal-3, PCIII and NTproBNP were tested by ROC curve analysis. Patients with missing data were excluded from the analysis. All data were analyzed with IBM SPSS version 25.0 .The baseline characteristics of the studied cohort are summarized in RV LGE was detected in all patients at surgical sites, more frequently located in the right ventricular outflow tract (RVOT) scar area (82.8%) and in the site of ventricular septal defect (VSD) patching (51.4%), but also in the anterior wall (65.7%), inferior wall (20%) and RV side of septum (54.2%) and in the RV-LV insertion points (88.5%). There was no LGE in the LV .The median RV fibrosis score was 8 points ). We studied the relations of RV fibrosis in two groups of patients: group of patients with low RV score (LGE RV < 8 points) and group of patients with high RV score (LGE RV ≥ 8 points).The association of LGE RV fibrosis score with clinical markers, CMR indices, and biomarkers is summarized in 2 compared to patients with low RV fibrosis score . RV myocardial fibrosis score was associated with RV dilatation and RV dysfunction based on RVEDVi, RVESVi, and RV ejection fraction measurements  ng/mL, median PCIII was 41.8  ng/mL and median NTproBNP was 143.4  pg/mL. There was no correlation between collagen biomarkers Gal-3 and PCIII, with NTproBNP.p = 0.21, (p < 0.044), (p = 0.05)) , . In ROC = 0.05)) .PCIII levels did not correlate with LGE scoring of RV, .NTproBNP levels were elevated in patients with high RV score, .p = 0.032, and total RV scoring . Areas of fibrosis are detected at the sites of surgery, mainly in the RV outflow tract and the interventricular septum around the ventricular septal defect patch region. Focal fibrosis can be identified using CMR and correlations with both systolic dysfunction and reduced exercise capacity and arrhythmias have been reported ,16. MyocThere is no proven treatment to improve RV function by targeting RV fibrosis, although preclinical studies have shown that Sodium-glucose transport protein 2 inhibitors have also demonstrated a positive effect in cardiac fibrosis ,22,23.Our data specifically support an association between RV myocardial fibrosis and impairment of RV function, independently of the first palliation or the highest number of surgeries . ExtendeGal-3 value of >7.42 pg/mL predicted moderate/severe PR in the studied cohort. In previous studies, Gal-3 has been studied as a biomarker of fibrosis with a prognostic role in HF mortality and rehospitalization and in congenital heart disease patients as a prognostic indicator in risk stratification ,30,31,32Previous studies in patients with rToF, reported that BNP levels are increased and associated with overload conditions and severity of PR ,34. NTprLevels of Procollagen III and Galectin 3 have been evaluated in HF studies and have been well associated with the prognosis of HF patients with normal cardiac anatomy, with Procollagen III being appreciated as a remodeling index . This fiBiomarker levels did not have a significant correlation with the extent of RV fibrosis in our study. An explanation for the discordance between the extent of RV fibrosis and biomarkers levels may be that in rToF the profibrotic damage-injury occurred at one single time point  whereas biomarker levels reflect the neurohormonal activation at the time of assessment. In contrast, in hypertensive patients there is continuous profibrotic damage-injury that constantly induces collagen deposition, and thus biomarker elevation.Cardiac magnetic resonance feature tracking analysis is progressively establishing its role as an accurate tool for quantitative evaluation of cardiovascular function by directly evaluating myocardial fiber deformation. Feature-tracking derived strain parameters are able to identify subtle myocardial abnormalities before overt clinical manifestation, thus allowing the early diagnosis of primitive cardiomyopathies, identification of cardiac involvement in systemic diseases, as well as risk stratification and monitoring of treatment effects in patients with heart failure of various etiologies . In the p = 0.844). RV EF is impaired decades after repair surgeries and RV FT-CMR analysis seems to mirror the effect of chronic pressure and/or volume load to RV, although without the ability to guide us regarding the RV performance and the adverse outcomes in this population.The longitudinal systolic strain of RV and LV was assessed using CMR FT. RV strain for our cohort was impaired when compared with published CMR strain values from healthy volunteers age 48 ± 13 years) [ years [1A significant impairment of all global strain parameters with echocardiography-based 2D strain analyses has been described in rToF patients who experienced death or sustained ventricular tachycardia . NumerouLV longitudinal systolic analysis showed that LV systolic dysfunction coexists with relatively preserved LV EF in adults with rToF and impaired RV EF. Although focal fibrosis was not detected in the LV in the present study, LV performance was affected, with a statistically significant difference between groups of patients with maximum and lower LGE RV scoring, indicative of adverse progressive ventricular–ventricular interaction ,26. ConsAdverse clinical outcomes in adult patients with rToF have been associated with LV dysfunction, with the reasons for left ventricular dysfunction poorly understood. LV displacement by 2D STE study, in a study from Diller et al.  with 413The novelty of our study is the correlation of the estimated focal RV fibrosis with the LV strain values and RV deterioration. A previous study of Hagdorn et al. in younger adults with rToF  reported that LV GLS values predict ventricular tachyarrhythmia, but not deterioration of ventricular function . A recenLarger prospective studies are needed with techniques such as CMR-FT, which are reproducible, quick, and easy to apply, in order to establish the prognostic role of biventricular GLS in risk stratification of the rToF aging population.Despite the perception of many that TOF is a mainly right-sided heart disease, various LV parameters have been associated with this outcome ,41. TherWe found that longitudinal strain analysis by CMR-FT of the LV was impaired in adults with rToF, despite the preserved LV EF and correlation with high RV fibrosis score. According to the normal values for ages <75 years old of the non-HF population (<125 pg/mL), mean values of NTproBNP levels in our study were increased (181.2 ± 178.4 pg/mL), with preserved LV EF. NTproBNP levels correlated significantly with high RV fibrosis score. In ROC curve analysis, a cut-off value of NTproBNP > 145pg/mL and a cut-off value of GLS LV −15.9% predicted LGE RV >8 points, reflecting the coexistence of the LV longitudinal systolic dysfunction due to ventricular–ventricular interaction and neurohormonal activation, as result of high RV fibrosis .We assume that further studies of LV GLS analysis and NTproBNP levels could contribute to the identification of early intervention time and risk stratification of adults with rToF.Our study has some limitations. The cohort of patients analyzed in this study does not reflect the entire spectrum of adult patients with rToF, as patients unsuitable for CMR assessment with gadolinium, including the higher risk patients with implantable cardioverter defibrillators, were excluded.Finally, we used the late gadolinium technique to assess the extent of regional myocardial fibrosis on CMR. T1 mapping sequences were not available in our site and therefore the assessment of diffuse myocardial fibrosis was not possible.A larger, prospectively followed-up cohort may provide further information on additional causes of fibrosis, its correlation with novel methods of RV and LV performance, as well as its prognostic power.A significant extent of RV fibrosis was mainly detected at surgical sites of RV. Gal-3, could serve as a blood collagen biomarker for the noninvasive assessment of volume overload due to significant PR in adults with rToF. RV fibrosis leads to impaired LV performance and possible neurohormonal activation. Non-invasive imaging with CMR, with the detection of myocardial fibrosis and strain analysis, could allow for a more refined timing of interventions such as PVR. A larger, prospectively followed-up cohort may provide further information concerning additional causes of RV fibrosis, the correlation of biomarker levels and strain analysis with CMR-FT, and their precise prognostic value.


Sleep-disordered breathing (SDB) comprising obstructive sleep apnea (OSA) is found in more than half of patients with heart failure (HF) and may have negative impacts on cardiovascular function. Increased atherosclerotic cardiovascular disease and the development of coronary events and congestive heart failure are associated with OSA. It is associated with a substandard quality of life, increased hospitalizations, and a poor prognosis. Despite its association with severe cardiovascular morbidity and mortality, the condition is frequently underdiagnosed. The substantial clinical evidence has established OSA as an independent risk factor for bradyarrhythmias and tachyarrhythmias in the last decade. The mechanisms which lead to such arrhythmias are uncertain. In short, OSA patients have a significantly elevated risk of HF and atrial fibrillation (AF). The direct correlation between HF, SDB, and cardiac arrhythmias has been poorly understood. The purpose of this study is to get a better understanding of the relation between AF, OSA, and HF by focusing on the pathophysiological mechanisms underlying these conditions. Therefore, we searched for articles to support our association in PubMed and Google Scholar databases. There is a diverse yet poorly defined relationship between heart failure (HF), sleep-disordered breathing (SDB), and cardiac arrhythmias .HF is a significant and rapidly increasing public health problem ,3. In deIn patients with HF, SDB is increasingly recognized as a predictor of poor prognosis and a disease process that may speed up the decline of heart function . More thCentral sleep apnea (CSA), obstructive sleep apnea (OSA), or a combination of the two are examples of SDB . AccordiPopulation-based studies identified numerous factors that change the atrial substrate  and increase AF vulnerability . ModifiaDespite existing research on the mechanisms of HF, OSA, and AF, evidence on the relationship between AF and OSA in HF patients is lacking. The pathophysiological pathways that predispose to the development of OSA and AF and how they are affected in HF patients will be reviewed and discussed in this article. We used PubMed and Google Scholar to find 46 articles relevant to our subject. We included ten papers after filtering papers written entirely in English and published during the last ten years.Classification of sleep-disordered breathing and definitionsOSA, CSA, or a combination of both are part of SDB . OSA chaCurrently, apnea is characterized by reduced airflow by at least 90% of the baseline pre-event for at least 10 seconds ,16. HypoInteraction between obstructive sleep apnea and heart failureOSA can, in many ways, accelerate the development of HF, as shown in Figure During inspiration, in cases of OSA, the negative intrathoracic pressure created by the respiratory muscles attempting to inspire against a closed airway increases venous return to the right heart, increases preload, and causes the septum to move to the left, which may compromise the role of the left ventricle (LV) . During In men without HF, we found that the amount of fluid displaced overnight from the legs correlated strongly with a rise in the circumference of the neck overnight and the frequency of hypopnea and obstructive apnea per hour of sleep  ,20. HencOSA is related to a rise in sympathetic activity, and this further contributes to extra peripheral vasoconstriction, tachycardia, and salt and water retention stimulation of the renin-angiotensin-aldosterone system (RAAS) . The damTherefore, in addition to the effects of neurohormonal modulators such as beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and aldosterone antagonists, SDB could be a potential therapeutic target for HF .Association of atrial fibrillation with obstructive sleep apneaGiven the high incidence of sleep apnea in HF patients, it is appropriate to inquire about any irregular breathing patterns during sleep from the patient's partner . When a AF is significantly more common in patients with OSA than in those without OSA, according to several findings ,23-26. AUsing 24-hour Holter monitoring, one of the first studies looked at the frequency of cardiac arrhythmias and conduction disturbance in 400 patients with OSA ,27. In tMechanism of atrial fibrillation in obstructive sleep apneaA variety of pathophysiological mechanisms may cause both OSA and AF; thus, the presence of one may promote the existence of the other . The mecAcute factors of OSA effecting onset of atrial fibrillationAcute factors directly associated with obstructive respiratory events can contribute significantly to the incidence of AF in OSA, such as changes in intrathoracic pressure, changes in blood gases, and sympathovagal imbalance .Changes in intrathoracic pressure: Obstructed inspirations cause significant intrathoracic pressure variations, resulting in changes in the transmural pressure of the heart, resulting in atrial stretch [ stretch . Arrhyth stretch . Orban a stretch ,32. The  stretch . They di stretch . Followi stretch . Repetit stretch .Blood gas changes: OSA causes frequent episodes of hypoxia and hypercapnia, which activate the chemoreflex and increase sympathetic nerve activity, causing tachycardia and high blood pressure, particularly at the end of apneic attacks [ attacks ,27,33. M attacks ,33,34.Sympatho-vagal imbalance: Direct muscle sympathetic nerve activity recordings showed increased sympathetic activation in OSA patients during apnea episodes [episodes ,35. Linzepisodes ,36,37.Long-term effects of OSA on atrial structural remodelingMajor atrial remodeling marked by 'atrial enlargement, local conduction disruptions and longer sinus node recovery,' atrial electromechanical delay, and left atrial dysfunction, is correlated with long-term OSA in patients ,34,38. SNeurohumoral activation and inflammation: OSA is related to elevations of circulating inflammation markers, and in patients who may undergo atrial structural and electrical remodeling, neurohumoral activation, namely the circulating RAAS combined with increased oxidative stress, has been demonstrated ,39-42.Impact of obesity and hypertension on structural remodeling: In the emergence of hypertension and the evolution of drug-resistant hypertension, OSA is considered an etiological factor ,43,44. CObstructive sleep apnea and atrial fibrillation in heart failureHF causes pulmonary congestion by increasing LV wall tension and LV filling pressures, stimulating lung irritant vagal receptors . The CheIn HF patients, OSA enhances sympathetic nervous system function, followed by several neurohumoral and hemodynamic responses, all of which contribute to the stress on the failing heart . Due to This paper aims to look into the pathophysiological mechanisms underlying OSA and AF in HF patients. We were able to demonstrate that OSA is associated with HF and contributes to AF through various means, including neurohumoral and hemodynamic changes in sympathetic, atrial structure, and electrical activity, as explained in the paper. Accordingly, cardiologists should have a high suspicion index for SDB in patients with HF and collaborate closely with sleep doctors to enhance patient care. As a result, it will be crucial for medical professionals to understand the mechanisms related to sleep apnea and cardiac arrhythmias in HF and to include them in diagnosis, since they are often underdiagnosed when considered independently. In this way, we can avoid complicated AF treatments and concentrate on sleep treatment to improve conditions related to sleep apnea. Early detection of risk factors can also help patients reduce their risk for AF and worsening of HF.


Progressive cardiomyopathy accounts for almost all mortality among Duchenne muscular dystrophy (DMD) patients. Thus, our aim was to comprehensively characterize myocardial involvement by investigating the heterogeneity of native T1 mapping in DMD patients using global and regional  analysis across a large cohort.We prospectively enrolled 99 DMD patients (8.8 ± 2.5 years) and 25 matched male healthy controls (9.5 ± 2.5 years). All subjects underwent cardiovascular magnetic resonance (CMR) with cine, T1 mapping and late gadolinium enhancement (LGE) sequences. Native T1 values based on the global and regional myocardium were measured, and LGE was defined.LGE was present in 49 (49%) DMD patients. Global native T1 values were significantly longer in LGE-positive (LGE +) patients than in healthy controls, both in basal slices  and in mid-level slices . No significant difference in global native T1 was found between healthy controls and LGE-negative (LGE−) patients. In segmental analysis, LGE + patients had significantly increased native T1 in all analyzed segments compared to the healthy control group. Meanwhile, the comparison between LGE− patients and healthy controls showed significantly elevated values only in the basal anterolateral segment . Interestingly, the epicardial layer had a significantly higher native T1 in LGE− patients than in healthy controls (p < 0.05), whereas no such pattern was noticed in the global myocardium. Epicardial layer native T1 resulted in the highest diagnostic performance for distinguishing between healthy controls and DMD patients in receiver operating curve analyses  when compared to global native T1 and endocardial layer native T1.Myocardial regional native T1, particularly epicardial native T1, seems to have potential as a novel robust marker of very early cardiac involvement in DMD patients.Trial registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx) ChiCTR1800018340, 09/12/2018, Retrospectively registered. Duchenne muscular dystrophy (DMD), an X-linked muscle degenerative disorder caused by deficient or defective synthesis of dystrophin protein, is the most common inherited muscular dystrophy and affects both skeletal muscle and myocardial muscle. Due to improved ventilatory assistance and supported treatments, cardiomyopathy has become the main cause of death in DMD patients , 2. HistFrom July 2018 to January 2020, 99 DMD patients were prospectively recruited for this Institutional Review Board (IRB)-approved study. DMD diagnosis was confirmed by genetic testing and/or skeletal muscle pathology in all patients. The exclusion criteria were claustrophobia; severe arrhythmia; contraindications for the use of contrast media, such as severe renal insufficiency; and inability to cooperate during CMR. Twenty-five age-matched healthy males undergoing CMR with gadolinium for a separate clinical indication with normal results and no evidence of cardiovascular disease were included as a control group. Their indications for CMR were: chest pain (N = 9); syncope (N = 4); occasional atrial premature beats (N = 5); and poor image quality on prior echocardiogram (N = 7). Every subject or guardian provided written informed consent form before CMR examination.2). Matched T1 mapping and LGE imaging sequences were performed at three standard short-axis levels  in the LV. Prior to contrast administration, native T1 mapping was performed using a modified Look-Locker inversion recovery (MOLLI) sequence with motion correction (MOCO) [2). LGE images were obtained 5–8 min after intravenous injection of gadolinium  at a dose of 0.15 mmol per kg body weight by using a single-shot phase-sensitive inversion recovery (PSIR) sequence . All images were acquired during breath holding in end-expiration, and electrocardiographic gating was used.CMR scanning was conducted using a clinical 3 T CMR scanner  equipped with an 18-channel receiver coil. CMR protocols included cine, T1 mapping, and LGE sequences. In order to quantify cardiac structure and function, 8–12 continuous sections were acquired from the mitral valve level to the LV apex in the short-axis view with a balanced steady-state free precession pulse (bSSFP) sequence  . The scaCMR analysis was performed offline by two experienced clinicians using commercially available software . The LV function parameters, including LV ejection fraction (LVEF), end-diastolic volume index (EDVI), end-systolic volume index (ESVI), and LV mass index (LVMI), were derived by defining the contours of the endo- and epicardial borders on the short-axis cine images according to current guidelines . LV dysfStatistical analyses were performed using SPSS software  and MedCalc . Continuous variables are presented as the mean value ± standard deviation (SD). Categorical variables are expressed as the frequency and percentage. Normality was evaluated using the Kolmogorov–Smirnov test, and homogeneity of variance was assessed using Levene’s test. Student’s t-test was used to compare normally distributed characteristics between DMD and controls. The demographics of DMD patients and healthy controls were compared using a Wilcoxon rank-sum test. The CMR results of DMD patients and healthy controls were compared using an independent t-test. One-way ANOVA was used to compare the CMR results among DMD subgroups and the healthy control group, and the Bonferroni correction was used for to adjust the post hoc pairwise tests for multiple comparisons. A paired t-test was used to compare the native T1 values of the endocardial and epicardial layers. Receiver operating characteristic (ROC) analysis with area under the curve (AUC) was used to identify the best discriminating parameter in the myocardial layers to differentiate between DMD patients and controls. Interobserver and intraobserver variability were calculated using the intraclass correlation coefficient (ICC). All tests were 2-sided, and a p-value < 0.05 was considered statistically significant.The baseline characteristics of the patients are shown in Table Among the 99 DMD patients, LGE was found to be present in 49 subjects (49%), defined as the LGE-positive (LGE +) group. The remaining 50 patients 51%) were assigned to the LGE-negative (LGE−) group. The baseline characteristics of LGE + patients were similar to those of LGE− patients, with the following exceptions: LGE + patients had a lower LVEF  and a significantly higher EDVI (p = 0.008) and ESVI (p < 0.001) than LGE− patients  and in the mid-level slices . A significant difference between LGE + and LGE− patients remained in the basal and mid-level slices . Although no significant difference was found, the global native T1 values of LGE− patients still tended to be higher than those of controls in both the basal  and middle slices .Native T1 values in different layers are depicted in Table 27/1188 segments of 99 patients and 3/300 segments of 25 healthy control subjects had to be excluded due to artifacts and incorrect motion correction. The mean native T1 value of each segment is presented in Fig. The intra- and interobserver reliability of the measurement of the global native T1, epicardial native T1, and endocardial native T1 are shown in Table This study demonstrates the value of a comprehensive CMR-based quantification of native T1 in the diagnosis of DMD. Compared with global native T1 values, regional native T1 values provide a superior way to distinguish DMD patients from controls. To the best of our knowledge, this is the first study to investigate a method for quantitative evaluation of native T1 in specific layers of the myocardium. Our patients covered a wide age range. Interestingly, myocardial LGE-negative segments in DMD with cardiac involvement showed higher T1 values than those of either DMD without cardiac involvement or controls, indicating that a diffuse ongoing process in the myocardium can be observed in this genetic disease. In addition, the study provides further evidence to support the contention that fibrotic substitution in the myocardium of DMD patients usually has a heterogeneous distribution and predominantly proceeds from the epicardium to the endocardium , 21.Despite advances in the diagnosis and management of DMD over the past 10 years, cardiomyopathy-related heart failure and arrhythmias are increasingly important sources of morbidity and mortality in DMD patients , 23. ThiThe native T1 values reported here are consistent with a recently published pediatric study by Maforo et al. using 3 T imaging . HoweverIn light of the current knowledge, averaging native T1 over the entire myocardium may not be sensitive enough to detect regional abnormalities; accordingly, we conducted a layer-specific analysis as well. The results of this study demonstrated significant differences in the epicardial layer between DMD subjects without cardiac involvement and controls. In addition, native T1 of the epicardial layer provides the greatest distinction between DMD patients and healthy controls. We hypothesized that native T1 of the epicardial layer could provide a superior way to distinguish DMD patients from healthy controls. Hence, although global values seem easier to manage, postprocessing that facilitates the use of segmental or layer-specific evaluations is required in the future.In postmortem hearts, it has already been demonstrated that myocardial damage starts in the subepicardial layer of the free wall with possible transmural extension in contiguous segments. This fibrotic change starts generally at the region behind the posterior and mitral valve apparatus and spreads downward progressively toward the apex , 24, 28.Our study has several limitations. First, apical segments were not considered due to the high exclusion rate , which prevents the AHA segmental analysis integrated. Additionally, the DMD group had significantly faster heart rates, which may influence the generalizability of our T1 mapping results . HoweverIn DMD patients, native T1 measurement by CMR is a useful tool in assessing myocardial fibrosis as well as detecting myocardial abnormalities even in the absence of LGE. Myocardial regional native T1, particularly epicardial native T1, seems to have potential as a novel robust marker of very early cardiac involvement in DMD.


Introduction: Takotsubo cardiomyopathy (TCM) or “stress cardiomyopathy” is an uncommon condition characterized by transient cardiac dysfunction with left ventricular apical ballooning in an appropriate clinical context. TCM has been observed in a variety of acute neurological conditions most prominently in patients with aneurysmal subarachnoid hemorrhage and status epilepticus. TCM has only been reported infrequently in association with traumatic brain injury (TBI). Herein we present a patient who developed TCM 3 days after hospital admission with severe TBI.Case Presentation: A 30-year-old male presented to the hospital with an acute subdural hematoma, anisocoria, declining consciousness and CT evidence of uncal herniation after being found down in a hotel room. The patient was taken emergently to the operating room for decompressive hemicraniectomy and hematoma evacuation. On the post-trauma day (PTD) 3, the patient developed acute dyspnea with increased oxygen requirements that improved with diuresis. On PTD 4, nursing staff noted T waive inversions (TWI) on the bedside monitor prompting an electrocardiogram (ECG) that showed a prolonged QTc interval and worsening TWI in leads I, II, aVL, and V2-6. Troponin I level was mildly elevated at 0.63ng/mL. Transthoracic echocardiography (TTE) was subsequently performed and showed a low ejection fraction (EF 26%) with apical hypokinesis and basal hyperkinesis, consistent with TCM. A diagnosis of TCM was confirmed by Cardiology consultation and he was started on a beta-blocker and an ACE inhibitor. Follow-up TTE on PTD 20 showed a normal left ventricular EF.Conclusion: While rarely reported in patients with TBI, TCM developed in an otherwise healthy young male following severe TBI necessitating decompressive hemicraniectomy. TTE should be considered in patients with TBI who have cardio-pulmonary symptoms or unexplained ECG abnormalities. Takotsubo cardiomyopathy (TCM) or “stress” cardiomyopathy is characterized by transient left ventricular dysfunction with apical hypokinesis and compensatory basal hyperkinesis on cardiac imaging. TCM typically occurs 1–5 days after the inciting stressor. It predominantly affects elderly females who have suffered from significant physical or emotional stress . The assA 30-year-old man with history of alcohol use was found unresponsive with unknown down time in his hotel room by the hotel staff. While his initial Glasgow Coma Score (GCS) was 13 at the scene, his GCS rapidly declined after arriving in the trauma bay and was emergently intubated for airway protection. Neurological examination revealed a fixed and dilated pupil on the left side with GCS of 6T after a brief sedation interruption . SecondaOn the early morning of PTD 3, the patient developed tachycardia and acute hypoxia. Chest X-ray demonstrated mild pulmonary edema bilaterally. ECG was obtained which revealed new QTc prolongation and T wave inversion (TWI) on the lateral leads .  His oxygOn the night of PTD4, the bedside nurse noted obvious TWI on the bedside monitor. That prompted a repeat ECG demonstrating a persistently prolonged QTc interval and worsening TWI on leads I, II, aVL, and V2-6.  The patiBy the next morning, repeat ECG was unchanged while troponin I downtrended to 0.54 ng/mL and then to 0.36 ng/mL. Repeat TTE was performed and demonstrated left ventricular apical ballooning with an estimated EF of 26% . ClinicaTakotsubo cardiomyopathy is a form of stress-induced cardiomyopathy that characteristically ensues a few days after an inciting physical or emotional stressor event. Although the precise incidence of TCM remains unknown, the literature suggests an incidence of between 15 and 30 cases per 100,000 per year in the United States . In a seAcute neurological disorders, including aneurysmal subarachnoid hemorrhage and status epilepticus are known to be strongly associated with TCM . One retThe brain-heart interaction has been proposed a long time ago, however, it is unclear as to why emotional and/or physical stress leads to cardiac dysfunction in some patients but not others. Twenty patients during the acute phase of TCM underwent functional MRI with the goal to identify which brain structures are associated with development of TCM . CompareThe essential elements in establishing a diagnosis of TCM is the demonstration of new-onset transient LV regional wall motion abnormalities that extend beyond a single coronary artery territory on cardiac imaging . An emotPatients with TCM are generally considered to have a good prognosis. In a prospective registry of 100 patients with TCM, 96 had recovery of cardiac function, although it might take a few weeks to months . ContempThis case emphasizes that TCM does occur in the setting of acute TBI. Although uncommonly reported, cardiac dysfunction may be more frequent than previously thought especially when sensitive methods for detecting left ventricular dysfunction are used. TCM should be considered as a recognized complication of TBI with the potential complications including manifestations related to impaired left ventricular function.The original contributions presented in the study are included in the article/Written informed consent was obtained from the patient for the publication of any potentially identifiable images or data included in this article.FW: study concept and design, data acquisition, first draft, and literature review. JD: study concept and design, literature review, and revision of the manuscript for intellectual content. All authors contributed to the article and approved the submitted version.Department of Critical Care Medicine at University of Pittsburgh Medical center will support publication fee.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Sensitivity and specificity were 67%  and 90%  for visual assessment, 51%  and 86%  for myocardial CT attenuation, 63%  and 84%  for TPR, and 78%  and 84%  for MPR, respectively. MPR showed higher diagnostic accuracy for detecting myocardial perfusion abnormality compared with myocardial CT attenuation and TPR.We evaluated the feasibility of myocardial perfusion ratio to the aorta (MPR) in static computed tomography perfusion (CTP) for detecting myocardial perfusion abnormalities assessed by single-photon emission computed tomography (SPECT). Twenty-five patients with suspected coronary artery disease who underwent dynamic CTP and SPECT were retrospectively evaluated. CTP images scanned at a sub-optimal phase for detecting myocardial perfusion abnormalities were selected from dynamic CTP images and used as static CTP images in the present study. The diagnostic accuracy of MPR derived from static CTP was compared to those of visual assessment and conventional quantitative parameters such as myocardial CT attenuation (HU) and transmural perfusion ratio (TPR). The area under the curve of MPR  was significantly higher than those of myocardial CT attenuation  and TPR  ( In coronary artery disease (CAD), it is important to assess the significance of myocardial ischemia to determine the optimal treatment strategy before revascularization ,2. In cuThis retrospective study was approved by our institution’s human research committee (registration number: 1810021). The need for informed consent was waived due to the retrospective nature of the study. Thirty patients from our cardiac database who underwent stress dynamic myocardial CTP and SPECT-MPI between February 2013 and March 2015 were enrolled in this study. In the present study, static myocardial CTP images were retrospectively extracted from dynamic myocardial CTP imaging data. The attending physician determined the indications for myocardial CTP and SPECT for the assessment of CAD due to effort angina via ST-T changes on electrocardiography, reduction in angina symptoms after administration of nitroglycerin, or multiple coronary risk factors. The exclusion criteria were as follows: (1) cardiomyopathy; (2) left ventricular ejection fraction <20%; (3) greater than first-degree atrioventricular block; (4) left complete bundle branch block; (5) valvular heart disease; (6) history of coronary artery bypass grafting; and (7) poor image quality of stress dynamic CTP and SPECT. The radiation exposure was calculated using the dose-length product with a conversion factor of 0.014, as described previously  H2O PET was variable even in healthy people [For static CTP imaging, myocardial CT attenuation is a simple quantitative parameter, but it is affected by various pathophysiological differences, such as the patient’s body weight and cardiac function . Indeed,y people . Tanabe y people . HoweverTPR is another quantitative parameter proposed in static CTP scans. TPR is a stable parameter that can be used to calculate the ratio of subendocardial CT attenuation to subepicardial CT attenuation . Yang etVisual assessment is a standard method for the assessment of static myocardial CTP imaging. According to our results, the visual assessment had higher specificity and lower sensitivity than the MPR. Yuehua et al. also reported a low sensitivity and high specificity of visual assessment  for detecting myocardial ischemia . The reaIn the present study, we suggested the MPR as a novel quantitative parameter for static myocardial CTP imaging. MPR has the potential to reveal myocardial perfusion abnormalities that may be difficult for conventional quantitative parameters  to detect. Then, MPR could be complementarily useful by utilizing the higher sensitivity for the cases in which myocardial perfusion abnormalities are not clearly detected by the visual assessment such as mild CAD in clinical practice. In a meta-analysis, myocardial CTP imaging had comparable diagnostic accuracy with conventional MPI  for detecting hemodynamically significant CAD . AdditioThis study had several limitations. First, it was a retrospective, single-center study with a small sample size. Second, we did not evaluate coronary CTA because we focused on the feasibility of MPR for detecting myocardial perfusion abnormalities in static myocardial CTP imaging. Third, patients with myocardial infarction were not excluded from the present study population, which might have led to the lower diagnostic accuracy of TPR. However, myocardial CTP imaging will be performed in patients with myocardial infarction in the real world, especially in patients with unrecognized myocardial infarction. Finally, the static CTP images were derived from the dynamic CTP data in the present study, and the scan parameters might not be optimal for static CTP imaging. Further studies are required to evaluate the feasibility of MPR in the optimal setting for static CTP imaging.In conclusion, MPR of the myocardium to the aorta using a timing bolus scan is a feasible quantitative parameter for assessing myocardial perfusion in static CTP imaging. MPR has a high diagnostic accuracy for detecting myocardial perfusion abnormalities, independent of substantial individual variations.


Type 2 diabetes mellitus (T2DM) is a major risk factor for coronary artery disease and myocardial infarction (MI). The interaction of diabetic cardiomyopathy and MI scars on myocardial deformation in T2DM patients is unclear. Therefore, we aimed to evaluate myocardial deformation using cardiac magnetic resonance (CMR) in T2DM patients with previous MI and investigated the influence of myocardial scar on left ventricular (LV) deformation.Overall, 202 T2DM patients, including 46 with MI (T2DM(MI+)) and 156 without MI (T2DM(MI−)), and 59 normal controls who underwent CMR scans were included. Myocardial scars were assessed by late gadolinium enhancement. LV function and deformation, including LV global function index, LV global peak strain (PS), peak systolic strain rate (PSSR), and peak diastolic strain rate (PDSR), were compared among these groups. Correlation and multivariate linear regression analyses were used to investigate the relationship between myocardial scars and LV deformation.p < 0.017) was observed in the T2DM(MI+) group with anterior wall infarction. The increased total LV infarct extent and infarct mass of LV were related to decreased LV global PS  and LV global PSSR . Multivariate analysis demonstrated that NYHA functional class and total LV infarct extent were independently associated with LV global radial PS  and circumferential PS , LV anterior wall infarction was independently associated with LV global longitudinal PS .Decreases were observed in LV function and LV global PS, PSSR, and PDSR in the T2DM(MI+) group compared with those of the other groups. Reduced LV deformation (The myocardial scarring size in T2DM patients after MI is negatively correlated with LV global PS and PSSR, particularly in the circumferential direction. Additionally, different MI regions have different effects on the reduction of LV deformation, and relevant clinical evaluations should be strengthened. Diabetic cardiomyopathy (DCM) is defined as myocardial dysfunction independent of coronary artery disease and hypertension that can lead to heart failure , 2. DiasCardiac magnetic resonance (CMR) imaging, which has been widely used in the last decades in clinical practice, provides information on various characteristics of cardiac structure, function, and myocardial tissue –12. CMR The study protocol was approved by Biomedical Research Ethics Committee of our hospital. Initially, we retrospectively enrolled 698 patients diagnosed with T2DM according to the World Health Organization standards between January 2015 and May 2021, and had completed CMR examinations . In addiClinical characteristics, family history, surgery history, medication, and serum biochemical indexes of all patients and healthy controls were collected. Blood sampling for serum biochemical indexes was performed within one week of the CMR scan without changing the subject's medication regimen.2, matrix size = 256 × 166). Gadobenate dimeglumine  was intravenously injected at a dose of 0.2 ml/kg body weight at an injection rate of 2.5–3.0 mL/s, followed by a 20 mL saline flush at a rate of 3.0 mL/s. LGE images were acquired in the corresponding slice position as the cine imaging 10–15 min after contrast injection. The images were obtained using a phase-sensitive inversion recovery sequence with the following parameters: temporal time = 300 ms, echo time = 1.44 ms, flip angle = 40°, slice thickness = 8 mm, field of view = 275 × 400 mm2, matrix size = 256 × 184.All subjects underwent CMR scan using a 3.0-T whole-body scanner  in the supine position. A standard ECG-triggering device was used, and end-inspiratory breath-holding was performed. Following a survey scan, cine images such as long-axis four-chamber views and short-axis two-chamber views were acquired using a steady-state free-precession sequence . Endocardial and epicardial traces were manually delineated by two experienced radiologists in the serial short-axis slices during the end-diastolic and end-systolic phases ; peak systolic strain rate (PSSR); and peak diastolic strain rate (PDSR) were acquired automatically. For LGE imaging analysis, LV segment–based analysis was performed in accordance with the 16-segment model of the American Heart Association. The hyper-enhanced myocardium area was defined as the myocardial scar on the LGE short-axis images when the signal intensity was five standard deviations above the mean intensity of the normal myocardium . Data were expressed in the format of mean ± standard deviations or median interquartile range for continuous variables and frequencies for categorical variables. One-way analysis of variance test was performed to evaluate the differences among the following groups: T2DM(MI+), T2DM(MI−) and normal control. Based on Bonferroni’s correction for multigroup comparisons, p-values of < 0.017 were considered statistically significant. Spearman’s and Pearson’s correlation analyses were conducted to identify the relationship between infarction and cardiac deformation. Pearson’s correlation was used between continuous variables and Spearman’s correlation was used to analyze the rank correlation Moreover, multivariable stepwise linear regression analysis was employed to identify the relationship between infarction parameters and cardiac dysfunction. Variables with a p-value of 0.1 in the univariable analyses were then included in a stepwise multivariable analysis based on a linear regression model. A p-value of < 0.05 was considered statistically significant.Of the 202 T2DM patients, 156 were in the T2DM(MI−) group (48[30.7%]) males, mean age 55.55 ± 11.80 years) and 46 in the T2DM(MI+) group (28[60.8%]) males, mean age 61.54 ± 9.11 years). Table In the T2DM(MI+) group, 20 patients received the percutaneous coronary intervention, and one patient received coronary artery bypass grafting surgery. Thirty-four patients were identified with culprit vessels, of which 14 (30.43%) were the left anterior descending coronary artery (LAD), 6 (13.0%) were the left circumflex coronary artery (LCx), and 14 (30.43%) were the right coronary artery (RCA).The CMR imaging results for LV function and deformation are summarized in Table p < 0.001) were lower in the T2DM(MI+) group than in the T2DM(MI−) and control groups. The global longitudinal PS (p < 0.017) was lower in the T2DM(MI−) group than in the control group. There was no statistically significant difference in global radial PS between the T2DM(MI−) and control group. The global radial, circumferential and longitudinal PSSR and PDSR  were significantly lower in the T2DM(MI+) group than in the T2DM(MI−) and control groups. Except for longitudinal PDSR in the T2DM(MI+) group compared with the T2DM(MI−) group. For the T2DM(MI−) group, the circumferential and longitudinal PDSR were lower than those in the control group (p < 0.017).Regarding LV deformation, the global radial, circumferential, and longitudinal PS  and LV global PS in all three directions , enhanced mass of LV , and enhanced area of LV  in T2DM(MI+) patients. However, LV global longitudinal PSSR and global PDSR in the three directions showed no significant relationship with infarction size .In this study, the range of infarct size of LV and total LV infarct extent were 17.96 (11.07–25.26) and 17.12 9.58–27.53), respectively. As shown in Table , respectp = 0.002; and β = − 0.446, p = 0.001, respectively; model R2 = 0.37) and global circumferential PS .Multivariate linear regression analysis in Table Regarding infarction-involved regions in the T2DM(MI+) group, 28 patients had LGE areas involving the interventricular septum, 20 involving the LV inferior wall, 13 involving the LV lateral wall, and 12 involving the LV anterior wall. No LGE areas were detected in the T2DM(MI−) group.p = 0.037), circumferential PS  . Patients with interventricular septum infarction have lower LV global longitudinal PS   and LV global deformation and peak strain rate. The study showed that the LV global PS in all three directions is significantly affected if MI is involved in the LV anterior wall. Furthermore, anterior wall involvement is an independent factor for the decrease in LV global longitudinal PS. Most of the culprit vessels involved the infarction of the LV anterior wall was LAD, whereas the right bundle branch and left anterior fascicular are slender, and the LAD is the main blood supply. When LAD stenosis and obstruction to the blood supply might affect LV deformation. Other studies have focused on the stratification effects of the size of MI on the prognosis and survival risk and found that MI size is an important predictor of the quality of life of patients , 30. HowThis study has several limitations. First, this study was a single-center study, so there may be some biases influencing the results. Second, the medication and NT-proBNP in the control group were not measured. However, the medical histories and the physical examination reports were carefully checked to ensure that they met the inclusion and exclusion criteria. Thirdly, as our study was a retrospective study, there are inherent design limitations, and the long-term development in T2DM patients after myocardial infarction should be further investigated in follow-up in the future. We aim to accomplish this in our future research endeavors.This study found that systolic dysfunction is more likely to occur in T2DM patients after MI, with a significant reduction in LV global circumferential deformation. The size of myocardial scarring is negatively correlated with the LV global PS and PSSR. In addition, MI in different regions has different effects on the reduction of LV deformation. Therefore, more attention should be paid to MI scarring and the extent of MI involvement in T2DM patients in clinical evaluations.


Non-ischemic cardiomyopathy (NICM) is one of the most important entities for arrhythmias and sudden cardiac death (SCD). Previous studies suggest a lower benefit of implantable cardioverter–defibrillator (ICD) therapy in patients with NICM as compared to ischemic cardiomyopathy (ICM). Nevertheless, current guidelines do not differentiate between the two subgroups in recommending ICD implantation. Hence, risk stratification is required to determine the subgroup of patients with NICM who will likely benefit from ICD therapy. Various predictors have been proposed, among others genetic mutations, left-ventricular ejection fraction (LVEF), left-ventricular end-diastolic volume (LVEDD), and T-wave alternans (TWA). In addition to these parameters, cardiovascular magnetic resonance imaging (CMR) has the potential to further improve risk stratification. CMR allows the comprehensive analysis of cardiac function and myocardial tissue composition. A range of CMR parameters have been associated with SCD. Applicable examples include late gadolinium enhancement (LGE), T1 relaxation times, and myocardial strain. This review evaluates the epidemiological aspects of SCD in NICM, the role of CMR for risk stratification, and resulting indications for ICD implantation. Sudden cardiac death (SCD) is one of the major causes of death accounting for approximately 15–20% of all deaths worldwide . It is cCurrent guidelines recommend ICD implantation for patients with symptomatic HF (NYHA Class II–III) and left-ventricular ejection fraction (LVEF) ≤ 35% under optimal medical treatment, referring to ischemic cardiomyopathy (ICM) as well as NICM . ConversOn top of that, the underlying causes for NICM and ICM are completely different. ICM results from coronary artery disease (CAD) and myocardial infarction. It is commonly assumed that ventricular arrhythmias (VA) originate from post-infarction scar in ICM, i.e., fibrosis ,10,11,12On the other hand, DCM as a major representative of NICM is characterized by a dilated left ventricle and systolic dysfunction after the exclusion of CAD, hypertension, and valvular disease . The undNearly one third (30%) of patients with DCM die of SCD , and DCMSubsequently, it has been assumed that the varying findings result from the different standard of medical care at the conduction time of the above-mentioned trials. For instance, only the minority of patients in the initial SCD-HeFT was treated with mineralocorticoid-receptor antagonists, and both in SCD-HeFT and DEFINITE, no cardiac resynchronization therapy (CRT) was used ,26,27.Various investigations already demonstrated the favorable effect of CRT on cardiac reverse modeling and outcome ,30,31. NOn top of that, by optimal medical treatment alone, one third of patients with idiopathic DCM exhibits reverse cardiac remodeling. As a consequence, cardiovascular mortality can be reduced by approximately 25% . In accoImportantly, ICD only protects from lethal arrhythmias, but not from other causes of cardiac death, e.g., acute HF, which is frequent in DCM patients . Thus, IFinally, adverse effects of ICD treatment have to be taken into account. After ICD-implantation, approximately 10% of patients experience at least one complication within the first 6 months . MoreoveThat raises the question of how to determine the subgroup of NICM patients most susceptible for arrhythmias and SCD who therefore might benefit the most from ICD implantation.Various possible predictors have been discussed in the past, to name but a few: Nonsustained ventricular tachycardia (NSVT), TWA, NYHA class, and QRS duration. The next section will give a short overview of the selected criteria and discuss the available risk scores. We chose especially NSVTs and TWA as representatives of electrical markers because of their clinical accessibility and their presence in recent meta-analyses ,25,42,43NSVTs occur in 40–60% of patients with idiopathic DCM  and haveTWA has also been discussed as valid risk predictor. It describes the morphologic change of the T-wave in every heartbeat . HoweverIn a recent meta-analysis, the authors analyzed possible predictors for VTs in DCM. They found a significant association for hypertension, genetic mutations , TWA, and the presence of LGE. Interestingly, family history of SCD and NYHA class did not fulfill statistical significance . AnotherLately, Younis et al. introduced two scores for VT/ventricular fibrillation (VF) vs. non-arrhythmic mortality based on all four MADIT trials and described a predictive value for sex, age, prior atrial arrhythmia, LVEF, systolic blood pressure, prior myocardial infarction, and heart rate. In accordance with the above-mentioned studies, older patients or patients with higher comorbidity burden  were less likely to benefit from ICD implantation . The scoIn about 30 to 50% of DCM patients, a positive family history can be found ,41. TodaLMNA encodes for two intermediate filament proteins, lamin A and C . These pFLNC is the underlying gene for the protein filamin C. Filamin C is actin binding and is thought to play an essential role in the integrity and signal transduction of cell–cell connections, in the Z-disc and between sarcomeres and the cell membrane ,67. A trRBM20 is involved in the post-transcriptional splicing of various proteins in cardiomyocytes, most notably titin and proteins regulating calcium homeostasis ,70,71. V2+-ATPase of the sarcoplasmatic reticulum, and its phosphorylation leads to muscle relaxation [The protein phospholamban with its underlying gene PLN also plays a role in the calcium homeostasis . Phospholaxation . When mulaxation . Mutatiolaxation ,77. It rlaxation .Global longitudinal strain (GLS) provided by speckle-tracking echocardiography (STE) is an evolving method for the evaluation of LVEF ,80. NikoWhen compared to CMR, the advantages of echocardiography remain the cost-effectiveness, higher availability, and the usability irrespective of renal function or cardiac devices affecting image quality ,84. HoweImpaired sympathetic innervation and activity result in heterogeneous electrical conductance, act as arrhythmic substrate, and are linked to increased risk of SCD ,88,89. ISo far, a variety of CMR-derived parameters have been evaluated for their usefulness in risk assessment for SCD in NICM patients. An overview of these parameters including limitations are provided in LGE imaging is an accurate and commonly applied technique for the identification of focal myocardial fibrosis and thus can visualize and quantify substrate for VA . LGE resp < 0.001) [In NICM, the prognostic value of LGE for adverse cardiovascular outcomes including SCD was shown in multiple studies, including two meta-analyses ,95. The < 0.001) .In addition, LGE was reported to be a strong independent predictor for VA and SCD after adjusting for other clinical or functional prognostic parameters ,100,101.For NIDCM in particular, the LGE-related risk for VA and SCD was also described by two meta-analyses ,98, sevep < 0.0001) [p = 0.64 vs. with LGE: HR = 0.45, 95% CI: 0.26–0.77, p = 0.003) [A severely reduced EF is the central parameter in current guidelines for risk stratification of SCD. However, evaluation of LGE as a risk predictor has not only yielded interesting results in patients with severely reduced EF but also in patients with mild to moderate LV dysfunction and even preserved EF. In DCM patients with an LVEF > 40%, LGE predicted the composite endpoint of SCD and aborted SCD  . A meta- 0.0001) . On the  0.0001) . In some 0.0001) . Likewis 0.0001) . A recen 0.0001) . Another= 0.003) .Electrophysiological studies using CMR-guided substrate ablation further support the inclusion of LGE into risk stratification. They indicate that LGE comes close to what is identified as arrhythmic substrate. LGE is displayed in the form of color-coded PSI maps which are obtained from high spatial resolution CMR images. They can be added to the navigation system to assist VT ablation and have a reasonably high correlation with the electroanatomic maps (EAMs). In a study with a mixed cohort of NICM and ICM patients, there was lower VT inducibility and fewer VT recurrences with CMR-aided substrate ablation than in the control group . The autOverall, there is substantial evidence for an association of LGE and risk for VA in NICM, which is also independent from traditional risk factors such as EF.Methods to assess LGE comprise visual analysis, the evaluation of signal intensity values of 2 to 6 standard deviations (SD) above the intensity of remote myocardium ,128,129,Studies have also assessed arrhythmic risk with respect to specific cut-offs in LGE extent. In a study population undergoing evaluation of ICD implantation, with half of patients suffering from ischemic heart disease, an LV scar size >5% was found to be the strongest predictor of the primary endpoint of death of VT or appropriate ICD discharge for VT. Patients with an LVEF > 30% and a scar with >5% of LV mass were determined to have a high risk for VA compared to patients with an LVEF < 30%. In contrast, patients with an LVEF < 30% and minimal or no scar had a low risk for VA, similar to those with an EF > 30% . HoweverIn a population with NICM, the percentage of LGE that predicted a primary outcome of death and hospitalization was 4.8% . Lehrke In addition to defining specific cut-offs, studies investigated a possible association of the transmurality of scars with adverse outcomes. In 26 NICM patients, a scar involving 26% to 75% of wall thickness was discovered to be the most significant predictor of inducible VT . In anotContrary to the above stated studies, others found only a limited value of LGE extent for prediction of SCD or VA ,113,136.In summary, the association of LGE extent and risk for VA still remains unclear. Although some studies report an incremental risk with greater LGE extent and similar cut-offs of around 5% of LV mass, other studies do not attribute additional prediction value to the extent of LGE on top of the presence of LGE alone.Beyond the presence and extent of LGE, the predictive value of location and pattern of LGE has also been investigated. The most common LGE patterns in NICM are linear midwall, subepicardial, or patchy enhancement patterns not following a coronary artery territory . Some paNICM patients with septal midwall LGE were reported to be at an increased risk for SCD ,107,109.In a different predictive model applied in NICM patients, coexistent septal LGE and free-wall LGE indicated a higher risk for SCD. The combination of LGE presence and location was superior to the combination of LGE extent and pattern . Out of Piers et al. compared a basal vs. non-basal distribution of LGE in NICM patients who underwent ICD implantation. They were followed for the occurrence of VA . Basallyp = 0.60) [Other studies have not demonstrated an association of LGE location and additional SCD risk in NICM and NIDCM ,117,137. = 0.60) .In summary, current data concerning the role of LGE localization and pattern are partly contradictory, and the distribution associated with the highest risk for VA is still unclear.Applying LGE as a risk predictor for the assessment of SCD holds limitations.First, there are limitations inherent to the technique of MRI , such asSecond, the different assessment methods to define scars make an overall comparison of results difficult. However, a meta-analysis could show that significant associations between LGE and VA or SCD were preserved in studies with visual analysis of LGE and in studies with threshold-based methods . ApproacThe second important CMR technique for the detection of myocardial fibrosis is T1 mapping and the assessment of extracellular volume fraction (ECV). In contrast to LGE, T1 mapping and ECV imaging are able to detect and to quantify diffuse myocardial fibrosis. Briefly, T1 mapping assesses longitudinal, T1 relaxation times of myocardial tissue. Absolute T1 relaxation times are illustrated pixel-wise on T1 maps. Myocardial T1 times reflect myocardial tissue composition and e.g., can be altered due to an excess in free water and collagen, but also protein, lipid, or iron deposition. Myocardial ECV can be estimated from myocardial and blood T1 times before and after contrast agent administration as well as the hematocrit and targets the relative proportion of myocardial extracellular space ,145. DifResults from ECV and T1 times analyses are especially valuable in NICM, as patients are suspected of having considerable diffuse fibrosis besides focal scarring , which hAbnormal T1 or ECV values were described as independent predictors for adverse clinical outcomes in various cardiomyopathies  and alsoIn NICM, ECV was shown to independently predict cardiovascular death, HF hospitalization, and appropriate ICD shock . In a lap = 0.021). Remarkably, the association persisted even after correction for LGE burden. ECV showed no association, which was probably due to procedure-related limitations such as contrast kinetics and variations in hematocrit levels [Studies investigating arrhythmic endpoints have also come to interesting results. In a mixed cohort of ICM and NICM patients undergoing ICD implantation, native T1 mapping was independently associated with an endpoint of appropriate ICD firing or documented sustained VT. Every increase of 10 ms in native T1 times increased the HR for VA by 1.06  in NICM by a different method without using a deformation analysis software ,170. TheTo our knowledge, a CMR study solely focusing on an arrhythmic endpoint in NICM has not been conducted. In post-infarct patients, an MR-tagging study showed that shorter time to peak circumferential shortening strain was associated with inducible VA .Overall, the results on strain in the risk assessment for VA are promising. However, the literature is still scarce, and further investigations are needed.Strain values vary depending on the assessment method and software version used . Thus, mIn conclusion, similar to EF where there is no available cut-off to discriminate patients at risk for sudden or non-sudden cardiac death , there iTo the best of our knowledge, for NIDCM, only one CMR-based risk score has been reported so far. The ESTIMATED Risk Score  is the fThe score was developed in 295 NICM patients without prior VA. 100 patients with documented VA were used for validation. The predictive value was assessed by comparing SCD events between high-risk patients defined by the score and the validation group. The score integrated LGE extent > 14%, syncope, atrial flutter/fibrillation, NSVT, advanced AV block, and age < 20 or >50 years. The extent of LGE strongly predicted SCD risk, while an LGE extent > 14% was not detected in the low-risk group but present in nearly 100% in the high-risk group. The most important limitations of the study were the small sample size and the unspecified SCD endpoint not restricted to sudden death due to tachyarrhythmias Apart from DCM, there is growing evidence for MR-based risk stratification for SCD in other NICM entities, especially in HCM and restrictive cardiomyopathy (RCM).LGE has been described in approximately 50% of HCM patients ,177. It Several studies have shown an association of LGE with increased risk for VA or SCD ,184,185,On the other hand, Maron et al. could not report LGE to be a risk factor for a composite primary endpoint of SCD, appropriate ICD discharge, and progressive HF symptoms of ≥1 NYHA class. Although patients with LGE reported a higher rate of adverse events compared to those without LGE, the comparison did not prove statistically significant .The above-mentioned studies hold limitations due to different scanning protocols and in particular due to different LGE assessment and quantification methods . As a reThe ESC 2014 guidelines stated that although LGE imaging might be useful in predicting cardiovascular mortality, the data did not allow using LGE in standardized risk prediction for SCD . In a stIn addition to LGE imaging, myocardial mapping and risk for VA have also been studied in HCM. One study found heightened T2 times consistent with myocardial edema to potentially increase the risk for SCD . AvanesoCMR studies could also report significant strain impairment in HCM ,195 and RCM is a heterogeneous disease that may overlap with HCM and can transform into a DCM phenotype. Various underlying etiologies can lead to RCM such as storage diseases  and infiltrative disorders  . In thisAlthough HCM and RCM represent different entities of myocardial diseases com-pared with NIDCM, the discussed CMR parameters are similarly helpful and applicable in risk stratification of SCD.Studies on NICM are mostly observational, single-center studies that are limited to a small sample size ,98 and lTo summarize, various reasons demand a new, precise risk score for SCD referring exclusively to NICM patients. First, the current clinical recommendations for ICD implantation focus on patients with LVEF ≤ 35%, despite a substantial proportion of patients at risk with higher LVEF and conflicting results of previous ICD trials addressing NICM. Second, NICM represents a heterogenous entity that substantially differs from ICM, needing targeted risk scores for each specific subtype . The fact that most studies mix DCM with other NICM patients possibly blurs results and hampers comparability. Finally, genetics and newer imaging modalities such as CMR or STE have not been incorporated in risk stratification tools and guidelines so far, despite increasing importance in clinical routine and mounting evidence supporting their use. Some genetic mutations such as LMNA, RBM20, FLNC, and PLN are clearly linked to arrhythmic phenotypes. CMR techniques including the presence, extent, and distribution of LGE, mapping, and strain have also been shown to add value to risk stratification. For a summary of all discussed risk parameters, see Investigations using CMR for risk stratification of SCD still lack larger prospective randomized trials . New insAll in all, to fill current knowledge gaps for risk stratification, future studies should focus only on patients with NICM and assess patients irrespective of LVEF. Such trials should evaluate on the one hand whether LGE can help to discriminate patients with ICD indication for primary prevention according to current guidelines who nevertheless may not benefit in terms of survival. On the other hand, studies should identify patients without ICD indication based on current guidelines, who are yet at increased risk for SCD and who might therefore benefit from ICD implantation. Finally, as no single risk factor to date has the discriminant power for safely identifying patients at risk for SCD, clinical, genetic, and imaging parameters should be considered simultaneously.