Background: The aim of the present study was to assess the role of 3 Tesla (3T) magnetic resonance imaging (MRI) in the assessment of infiltrative cardiomyopathy (ICM).Methods: Cardiac MRI was performed on a 3T MRI machine for 15 patients who had clinical or echocardiographic signs of infiltrative cardiomyopathy. Each scan was assessed on a set of anatomical and functional parameters. The patterns of left ventricular (LV) late gadolinium enhancement (LGE) were also analyzed.Results: Bi-atrial dilatation was noted in 14 patients, consistent with a restrictive phenotype. All 15 patients had diastolic dysfunction with reduced LV diastolic ventricular filling and prolonged peak filling times. Eleven patients had a decreased peak filling rate. Twelve patients had systolic dysfunction with reduced ejection fraction (EF). Ten patients had contractile dysfunction in the form of global LV hypokinesia. On delayed contrast imaging, four patients showed no abnormal LGE. Two patients showed diffuse subendocardial enhancement. Two patients showed patchy subendocardial enhancement. Six patients showed patchy mid-myocardial enhancement. One patient showed diffuse mid-myocardial enhancement. Three patients showed patchy subepicardial enhancement. Two patients showed patchy transmural enhancement. Three patients showed reversed myocardial nulling. All 15 patients received a provisional diagnosis of infiltrative cardiomyopathy on the basis of cardiac MRI findings. Sarcoidosis was given as a probable cause in four patients, amyloidosis in three patients, an infectious cause in two patients, and drug-induced cardiomyopathy in one patient. In five patients, no obvious cause could be identified.Conclusion: Infiltrative cardiomyopathies, although relatively uncommon, pose significant challenges in diagnosis and treatment. Cardiac MRI has become the gold standard for non-invasive diagnosis of all infiltrative cardiomyopathies. Cardiomyopathies are a significant contributor to cardiovascular mortality and morbidity worldwide . They arRCMs are a diverse group of diseases whose hallmark is diastolic dysfunction (due to restrictive filling) with relatively maintained systolic function . They arDiagnosing ICM requires a high level of clinical suspicion; further investigations include transthoracic echocardiography (TTE), cardiac magnetic resonance imaging (MRI), and radionuclide imaging techniques such as positron emission tomography (PET) scans, and endomyocardial biopsy.Cardiovascular magnetic resonance (CMR) imaging, with its superior spatial and tissue resolution, has become the major diagnostic modality in the evaluation of RCM and ICM. It is a non-invasive and non-ionizing imaging technique that has greatly revolutionised the diagnosis and follow-up of ICMs. It can definitively establish the diagnosis in suspected or clinical cases, assess the severity of the disease both qualitatively and quantitatively, check for complications and other systemic disease manifestations, provide prognostic information, and help in future follow-ups.CMR can assess cardiac chamber size, morphology, and function and accurately quantify ventricular and atrial volumes. It can determine both systolic and diastolic function and calculate the ejection fraction (EF), end systolic volume (ESV) and end diastolic volume (EDV). Diastolic dysfunction, the defining feature of RCM, can be further assessed by ventricular filling on cine MRI and with parameters such as peak filling rate and peak filling time. Associated valvular dysfunction and wall motion abnormalities can also be observed. Features diagnostic of ICM on CMR include dilatation of both atria with relatively preserved ventricular size, thickening of the left ventricular (LV) wall, and diastolic dysfunction with relatively normal systolic function. However, advanced or severe cases of ICM show systolic dysfunction. Through its much larger fields of view, CMR can also demonstrate the involvement of the adjacent mediastinum and lungs in various ICMs.The use of late gadolinium enhancement (LGE) has significantly improved the diagnostic capacity of CMR. Based on the LGE pattern, it is possible to differentiate various forms of infiltration and thus accurately establish the underlying aetiology.The myocardial LGE pattern also helps to differentiate ICM from ischemic cardiomyopathy. LGE also provides prognostic information for different ICMs. CMR also allows for easy evaluation of the pericardium and can also differentiate between ICM and constrictive pericarditis. CMR can also help us conclusively rule out other differential diagnoses of dilated or hypertrophic cardiomyopathy in equivocal cases.This study aims to assess the role of CMR imaging in the diagnosis of ICMs.This descriptive observational study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Center, Pimpri, Pune, India, from August 2020 to July 2022, and 15 patients were included in the study. Clearance from the Institutional Ethics Subcommittee of Dr. D. Y. Patil Medical College, Hospital and Research Center was obtained beforehand .Inclusion and exclusion criteriaThe following inclusion criteria were used: (i) Clinical suspicion or echocardiographic evidence of iICM, (ii) Suspicion of myocardial infiltration in known cases of systemic infiltrative diseases such as hemochromatosis, amyloidosis, or sarcoidosis, and (iii) Evaluation of the severity of cardiac involvement in known cases of ICM. Patients with MRI-incompatible metallic implants were not included in the study. Hemodynamically unstable, claustrophobic or uncooperative patients, and chronic kidney disease patients with a severely decreased estimated glomerular filtration rate (eGFR) were also excluded from the study. Pediatric patients with thalassemia major and suspected iron overload cardiomyopathy who underwent cardiovascular T2-star (T2*) imaging were also not included in the study.TechniqueA MAGNETOM Vida 3 Tesla (3T) MRI scanner  was used for the scans. A three-plane steady-state free precession (SSFP) localizer was taken initially to localise and plan the sequences.Pre-Contrast Scanning1. Sequences used for cardiac morphology: T2 true fast imaging with steady-state free precession (TRUFI) single shot, T2 half-Fourier acquisition single-shot turbo spin-echo (HASTE) dark blood, T1 turbo spin-echo (TSE) dark blood, T2 TSE dark blood, T2 short tau inversion recovery (STIR) dark blood long axis 2. Sequences used for cardiac function: Cine sequences include two-chamber cine TRUFI long axis, Four-chamber cine TRUFI long axis, Cine TRUFI retro short axis, Cine left ventricular outflow tract (LVOT), and Cine right ventricular outflow tract (RVOT)Post-Contrast ScanningPost-contrast cardiac imaging was done using IV dimeglumine gadopentetate as the contrast agent (0.1 mmol/kg body weight). DYNAMIC TRUFI SR EPAT sequence was used for perfusion. For assessment of delayed enhancement, a short axis inversion scout sequence (TI scout) was taken 10 minutes post-gadolinium to identify the optimal TI value to null the signal from the normal myocardium. Based on the optimal TI value obtained, delayed TRUFI high-resolution phase-sensitive inversion recovery (PSIR) sequences were taken in two-chamber view, four-chamber view, and short axis view to obtain both magnitude and real images.Retrospective electrocardiogram (ECG) gating was used for all image acquisition. Each scan was assessed on set anatomical and functional parameters. The patterns of left ventricular LGE were also analysed.A total of 15 patients were evaluated. The mean age was 49 years, ranging from 13 to 80 years. Seven patients were males (47%), and eight were females (53%). Fourteen patients had cardiac symptoms, the most common being dyspnea. One patient had no cardiac symptoms but was a known case of multiple myeloma. Seven patients had mild cardiomegaly. Seven patients had moderate cardiomegaly. One patient had gross cardiomegaly. Right and left atria were dilated in 14 patients, consistent with a restrictive phenotype . Four patients had LV hypertrophy, with a mean LV wall thickness of 20.5 ±9.34 mm . Twelve patients had systolic dysfunction with reduced EF (EF ≤ 55%), with the mean EF being 36.25±9.96% . Three patients had normal systolic function with preserved EF. All 15 patients had diastolic dysfunction, as ascertained by the visual evaluation of reduced LV diastolic ventricular filling on cine MRI images. All 15 patients showed prolonged peak filling times, with mean value being 498.26 milliseconds (ms), range 346-818 ms . Eleven patients had a decreased peak filling rate (PFR < 2.4 EDV). Four patients had normal PFR (2.4-3.6 EDV).Valvular dysfunction in the form of mitral or tricuspid regurgitation was seen in 13 patients. Five patients had no wall motion abnormality. Ten patients had contractile dysfunction in the form of global LV hypokinesia. On evaluation of LV LGE patterns, four patients showed no abnormal LGE. Two patients showed diffuse subendocardial enhancement Figure . Two patFigure Reversed myocardial nulling was seen in three patients Figure , all of Pericardial effusion was seen in 10 patients Figures , 3. PeriAll 15 patients received a provisional diagnosis of ICM on cardiac MRI. Based on the pattern of enhancement, the presence or absence of reversed myocardial nulling, and other associated pulmonary and mediastinal findings, sarcoidosis was given as a probable cause in four patients, amyloidosis in three patients, an infectious cause in two patients, and drug-induced cardiomyopathy in one patient. In five patients, no obvious cause could be identified.In recent years, CMR has become the major diagnostic modality in the evaluation of RCM and ICM. Cardiac MRI in ICM primarily shows dilatation of both the atria and diastolic dysfunction . In our The LV wall can be thickened in ICM  because of the underlying infiltrative process, such as in amyloidosis, or it can be normal . VentricDiastolic dysfunction, a chief criterion for ICM, can be assessed by a reduction in visual diastolic ventricular filling on cine MRI images, a prolonged peak filling time, and a decreased peak filling rate. Systolic function is relatively normal in cases with ICM. However, severe or advanced cases often show reduced LV systolic function. Global or regional wall motion abnormalities are also seen in many cases of ICM due to wall infiltration.In our study, all 15 patients had diastolic dysfunction, as ascertained by the visual evaluation of reduced LV diastolic ventricular filling on cine MRI images. All 15 patients showed prolonged peak filling times, with mean value being 498.26 milliseconds (ms), range 346-818 ms . Eleven patients had a decreased peak filling rate ( < 2.4 EDV). Four patients had normal peak filling rates (2.4-3.6 EDV). These suggest that peak filling time and peak filling rate can be used as useful CMR indicators for diastolic dysfunction. This is consistent with multiple studies that have found that a lower peak filling rate and a longer time to peak filling rate are useful indicators of diastolic dysfunction on CMR [The absence of features such as pericardial thickening, septal flattening, or inversion on CMR helps in definitively differentiating ICM from constrictive pericarditis . The useThe diagnosis of cardiac amyloidosis is based on strong clinical suspicion and aided by the use of multimodality imaging, including a focused echocardiogram, technetium pyrophosphate scan, and above all, a dedicated CMR . AccordiThe presence of myocardial amyloidosis might be identified using the reversed nulling pattern on the TI scout sequence CMR, according to research by Pandey et al. . They obAdditional findings described in cardiac amyloidosis include thickening and LGE of the atria , and thiIn their study evaluating the role of CMR in cardiac sarcoidosis, Matoh et al. found LGE in five out of 12 patients . In our Additionally, Vignaux et al. discovered that congestive cardiomyopathy with heart failure and widespread myocardial thickening with diffuse contraction anomalies may occasionally result from large infiltration with severe cardiac involvement . In our Multiple associated extra-cardiac findings are often helpful in strengthening the diagnosis of cardiac sarcoidosis in patients with characteristic LGE patterns on CMR. Intrathoracic lymphadenopathy is the most common finding in sarcoidosis . In our All 15 patients evaluated in our study received a provisional diagnosis of ICM on cardiac MRI. Among these, 12 patients had been identified as having a restrictive phenotype on two-dimensional (2D) echocardiography. This indicates that cardiac MRI shows 100% sensitivity and specificity in diagnosing ICMs and can further help in characterizing the aetiology. One patient had been given a diagnosis of constrictive pericarditis on 2D echocardiography. On cardiac MRI, however, he was diagnosed with ICM mostly secondary to infection (myopericarditis), in view of pericardial thickness < 4 mm and the absence of diastolic interventricular septal flattening. This is consistent with the findings of Farcone et al., who found early diastolic septal inversion or flattening at the onset of inspiration in all cases of constrictive pericarditis and in no case of RCM .One patient had been diagnosed with hypertrophic obstructive cardiomyopathy on 2D echocardiography. Cardiac MRI, however, indicated findings suggestive of ICM, with dilatation of the left atrium and left ventricle, global hypokinesia, and extensive patchy mid-myocardial and transmural scarring showing LGE in multiple segments of the basal, mid, and apical cavities. There was no obvious asymmetrical septal or LV wall hypertrophy. Also, no obvious systolic anterior motion of the mitral valve was noted.A patient found to have only LV hypertrophy with systolic dysfunction on 2D echocardiography was suggested a diagnosis of RCM based on biatrial dilatation, prolonged peak filling time (546 milliseconds), decreased peak filling rate (< 2.4 EDV), and a reduction in visual diastolic ventricular filling on cine MRI images.Our study had some limitations that may affect the generalizability and validity of our findings. Firstly, we had a small sample size that did not include all types of ICMs. Also, in our institute, patients with iron overload cardiomyopathy  only undergo cardiac T2* imaging and not a detailed CMR scan due to cost concerns. Hence, they could not be included in the study. Secondly, we could not obtain histologic confirmation in most patients. Thirdly, the high cost of conducting the study, the relative lack of awareness about the importance of cardiac MRI in ICM among referring clinicians, and the inability of a few patients to hold their breath for sufficient periods of time, all contributed to patient attrition in the study. Therefore, further studies with larger and more diverse samples are needed to confirm our findings.ICMs, although relatively uncommon, pose significant challenges in diagnosis and treatment. Early detection is important to institute timely intervention and avoid irreversible damage. Cardiac MRI has become the gold standard for non-invasive diagnosis of all ICMs. Not only does it offer the advantage of being non-ionizing and highly reproducible, but it is also highly accurate, sensitive, and specific. It can help establish a definitive diagnosis in suspected cases and also identify the underlying aetiology. It can also assess disease activity and severity and check for complications. It also provides prognostic information and allows for the evaluation of treatment response.


Recent studies have reported atrial involvement and coexistence of aortic stenosis in transthyretin (ATTR) cardiac amyloidosis (CA). However, pathological reports of extraventricular ATTR amyloid deposits in atrial structures or heart valves are limited, and the clinical implications of ATTR amyloid deposits outside the ventricles are not fully elucidated.99mtechnetium-pyrophosphate scintigraphy, cardiac magnetic resonance, endomyocardial biopsy and their mid-term clinical course up to 5 years. These findings suggested that these were extraventricular ATTR amyloid deposits localized in the aortic valve and the left atrium.We report 3 cases of extraventricular ATTR amyloid deposits confirmed in surgically resected aortic valves and left atrial structures, all of which were unlikely to have significant ATTR amyloidosis infiltrating the ventricles as determined by multimodality evaluation including While long-term observation is required to fully clarify whether these extraventricular ATTR amyloid deposits are truly localized outside the ventricles or are early stages of ATTR-CA infiltrating the ventricles, our 3 cases with multimodality evaluations and mid-term follow up suggest the existence of extraventricular ATTR amyloid deposits localized in the aortic valve and left atrial structures. Recent studies have reported atrial involvement and coexistence of aortic stenosis (AS) in transthyretin (ATTR) cardiac amyloidosis (CA) –7. HowevHerein, we report 3 cases of pathologically diagnosed extraventricular ATTR amyloid deposits in surgically resected aortic valves and left atrial structures, which suggested the existence of extraventricular ATTR amyloid deposits localized in the aortic valve and left atrial (LA) structures.2) and moderate mitral regurgitation  and elevated B-type natriuretic peptide . Echocardiogram showed left ventricular (LV) ejection fraction (EF) 26%, LV end-diastolic/end-systolic dimension (LVEDD/ESD) 57/48 mm, interventricular septum/posterior wall thickness (IVS/PWT) 12/10 mm, global longitudinal strain (GLS) -4.4%, severe AS  0.37 cm99mTechnetium-pyrophosphate (99mTc-PYP) scintigraphy showed no atrial or ventricular uptake, and cardiac magnetic resonance (CMR) showed no late gadolinium enhancement (LGE) and normal extracellular volume fraction (29.9%), suggesting that ATTR-CA infiltrating the ventricles was unlikely  and normal BNP (16.5 pg/ml). Transesophageal echocardiogram and contrast-enhanced computed tomography revealed a 9-mm pedunculated mobile mass in the LA next to the LA appendage, which was suspected to be the source of emboli . Perioperative evaluations for LV hypertrophy included CMR showing asymmetric septal hypertrophy (septum thickness 15 mm) with no LGE  was admitted for dyspnea on exertion. Troponin T was normal (0.008 ng/ml), and BNP was elevated (261.4 pg/ml). Echocardiogram Fig. A showed LGE Fig. A, and riLGE Fig. B. For drPathology of the aortic valve showed patchy ATTR amyloid deposits Fig. C. The myWe report 3 cases of extraventricular ATTR amyloid deposits confirmed in surgically resected aortic valves and LA structures, all of which were unlikely to have ATTR amyloidosis infiltrating the ventricles as determined by multimodality evaluation and mid-term clinical course up to 5 years  , 9, have99mTc-PYP scintigraphy that 58 patients had atrial uptake without ventricular uptake, while 105 patients had ventricular uptake without atrial uptake, indicating that atrial involvement may not necessarily precede ventricular involvement.Di Bella et al. reported in 2018 that atrial involvement in ATTR-CA is an early stage of ATTR-CA . HoweverAs ATTR amyloids are believed to be derived and formed from circulating transthyretin protein synthesized by the liver, ATTR amyloid deposits in the atrium may be a part of systemic disease and ATTR amyloid deposits could be found in other tissue sites after long-term follow up. However, our findings support the possibility that they could be localized atrial ATTR amyloid deposits. While the clinical significance of atrial ATTR amyloid deposits has not been fully elucidated and long-term close follow-up may be justified at this point, our 2 cases of surgically resected ATTR amyloid deposits in the atrium with mid-term prospective follow up, the first to be reported with multimodality evaluations, suggest the possibility of extraventricular ATTR amyloid deposits localized in the atrium.While various types of amyloid deposits including light-chain (AL), amyloid A protein (AA) and Apo-AI have been reported in surgically resected aortic valves and autopsy studies, very few histological reports of ATTR amyloid in the aortic valve have been published –19, and Recently, Singal et al. studied 46 surgically resected aortic valves with concomitant ventricular biopsy and reported that 33 (71.7%) had aortic valvular amyloid deposits (including 19 ATTR derived); however, none had amyloid deposits in the ventricle, and they concluded that the majority were “isolated valvular ATTR amyloid deposits” [Similar to the discussion with ATTR amyloid deposits in the atrium, deposition of ATTR amyloid is believed to be a systemic process, thus we could not rule out the possibility that valvular ATTR amyloid deposit is an early stage of ATTR-CA (infiltrating the ventricles) without long-term follow up. However, our cases suggest the possibility that they could be localized valvular ATTR amyloid deposits. Our findings also suggests that, to understand the pathophysiology of patients with concomitant AS and ATTR-CA, the existence of amyloid deposits localized in the valves should be taken into consideration.While clinical implications of extraventricular ATTR amyloid deposits localized outside the ventricles are not fully elucidated, our cases are the first detailed report of surgically resected cases and with mid-term follow up (up to 5 years), which suggested the existence of extraventricular ATTR amyloid deposits localized in the aortic valve and the atrial structures. Diagnosis of amyloid deposits were confirmed by Congo red or direct fast scarlet staining, followed by immunohistochemistry staining for ATTR and AANP. Mass spectrometry or immunoelectron microscopy was unavailable in our patients, which might have provided further insights because of their proven superior sensitivity compared to immunohistochemistry , 21.It could be hypothesized that our cases were localized amyloid deposits rather than an early ATTR-CA, and raises the possibility of localized “innocent” deposits not strictly related to systemic deposition as reported in literatures , 22–24.


However, there have been few studies in which the association between systemic VO2 and BT in humans was investigated in a wide range of BTs. The aims of this study were 1) to determine the association between VO2 and age and 2) to determine the association between VO2 and BT.Body temperature (BT) is thought to have associations with oxygen consumption . The associations of VO2 with age and BT were examined using spline regression and multivariable regression analysis with a random effect.This study was a retrospective study of patients who underwent surgery under general anesthesia at a tertiary teaching hospital. VO2 was reduced by 2.1 ml/kg/min with one year of age (p < 0.001) among patients less than 18 years of age and that there was no significant change in VO2 among patients 18 years of age or older . VO2 in all bands of BT < 36.0 °C was not significantly different from VO2 in BT >  = 36 °C and < 36.5 °C. Multivariable linear regression analysis showed that compared with VO2 in BT >  = 36 °C and < 36.5 °C as a reference, VO2 levels were significantly higher by 0.57 ml/kg/min in BT >  = 36.5 °C and < 37 °C (p < 0.001), by 1.8 ml/kg/min in BT >  = 37 °C and < 37.5 °C (p < 0.001), by 3.6 ml/kg/min in BT >  = 37.5 °C and < 38 °C (p < 0.001), by 4.9 ml/kg/min in BT >  = 38 °C and < 38.5 °C (p < 0.001), and by 5.7 ml/kg/min in BT >  = 38.5 °C (p < 0.001). The associations between VO2 and BT were significantly different among categorized age groups (p = 0.03).A total of 7,567 cases were included in this study. A linear spline with one knot shows that VO2 increases in parallel with increase in body temperature in a hyperthermic state but remains constant in a hypothermic state. Neonates and infants, who have high VO2, may have a large systemic organ response in VO2 to change in BT.VOThe online version contains supplementary material available at 10.1186/s12871-023-02182-1. Since inadequate oxygen delivery for VO2 has been shown to be related to a severe condition of the patient and poor outcomes, one of the main goals in the operating room and intensive care unit is to maintain the balance of systemic oxygen supply and VO2 , VO2 levels were significantly higher in BT >  = 36.5 °C and < 37 °C , BT >  = 37 °C and < 37.5 °C , BT >  = 37.5 °C and < 38 °C , BT >  = 38 °C and < 38.5 °C , and BT >  = 38.5 . VO2 in all bands of BT < 36.0 °C was not significantly different from VO2 in BT >  = 36 °C and < 36.5 °C.Figure 2 in BT >  = 36 °C and < 36.5 °C as a reference, VO2 levels were significantly higher by 0.57 ml/kg/min in BT >  = 36.5 °C and < 37 °C (p < 0.001), by 1.8 ml/kg/min in BT >  = 37 °C and < 37.5 °C (p < 0.001), by 3.6 ml/kg/min in BT >  = 37.5 °C and < 38 °C (p < 0.001), by 4.9 ml/kg/min in BT >  = 38 °C and < 38.5 °C (p < 0.001), and by 5.7 ml/kg/min in BT >  = 38.5 °C (p < 0.001).The result of the linear mixed effects model is shown in Table 2 measured and BT are shown in Supplemental Fig. S2 in BT >  = 36 °C and < 36.5 °C as a reference, VO2 levels were significantly higher in BT >  = 37.5 °C and < 38 °C, BT >  = 38 °C and < 38.5 °C, and BT >  = 38.5. In patients between one and five years old and patients between five and 18 years old, compared with VO2 in BT >  = 36 °C and < 36.5 °C as a reference, VO2 levels were significantly higher in BT >  = 37 °C and < 37.5 °C, BT >  = 37.5 °C and < 38 °C, BT >  = 38 °C and < 38.5 °C, and BT >  = 38.5. In patients 18 years old or older, compared with VO2 in BT >  = 36 °C and < 36.5 °C as a reference, VO2 levels were significantly higher in BT >  = 36.5 °C and < 37 °C, BT >  = 37 °C and < 37.5 °C, BT >  = 37.5 °C and < 38 °C, BT >  = 38 °C and < 38.5 °C, and BT >  = 38.5. The associations between VO2 and BT were significantly different among the groups (p = 0.03). The results of the linear mixed effects models in the subgroups are shown in Supplemental Table SResults of subgroup analyses for the associations between VO2 with advance of age among patients less than 18 years of age but that there was no association between VO2 and age among patients 18 years of age or older. VO2 increased in parallel with increase in BT when BT was above 36.5 °C, but there was no significant change in VO2 when BT was below 36 °C. However, there were significant differences in the association between VO2 and BT among categorized age groups.In this retrospective study, we found that there was a significant reduction in VO2 was relatively stable and that there was no significant association between VO2 and age under the condition of normothermia in patients >  = 18 years of age. Linear mixed effects models with adjustment for body temperature also showed significantly higher VO2 in patients < 1 year of age, patients >  = 1 year of age and < 5 years of age, and patients >  = 5 years of age and < 18 years of age than that in patients >  = 18 years of age. The results showing high VO2 in children in this study are consistent with the results of previous studies [2, especially among pediatrics, we have a concern about the reliability of measurements. VO2 measurements based on Sykes’ formula might be affected by the percentage of dead space and the levels of precision of flowmeters and ventilators [We found that VO studies , 17. Howtilators . Errors 2 and BT is an issue of main interest in this study. There have been only a few studies in which the association between VO2 and temperature as a continuous variable or finely categorized variable was assessed, and the results were conflicting. Bacher et al. conducted a prospective study including 19 adult patients who underwent intracranial surgery and found that VO2 showed a trend for continuous decline with decrease in body temperature from 35.5 °C to 32.0 °C in a hypothermic group [2 between BTs of 33 °C and 37.6 °C, but they did not perform statistical analysis of the changes in VO2 [2 after cardiopulmonary bypass in 20 children with congenital heart disease. In their observational study, the peak increase in VO2 was significantly correlated with the peak increase in central temperature between 36.6 °C and 38.4 °C [2 progressively decreased with hypothermia but showed smaller changes below 35 °C with no significant difference among the groups at BT below 35 °C [2 with hyperthermia but not with hypothermia are consistent with the results of the studies by Tokutomi et al. and Li et al.[The association between VOic group . Holzings in VO2 . Li et a 38.4 °C . Tokutomow 35 °C . Our resLi et al., 23.2 and BT using a large number of subjects and our results suggested that hyperthermia increases VO2, but hypothermia does not reduce VO2. There are some explanations for our findings. First, hyperthermia increases VO2, but hypothermia below normal body temperature does not further decrease VO2 by systemic organs among patients under general anesthesia. All patients who underwent general anesthesia, not only patients with brain injury, were eligible for this study. Since sedation and neuromuscular blockade reduce VO2, VO2 in the patients in our study was considered to have been significantly suppressed [2 decreased by a third after induction of anesthesia in elderly patients [2 might not be possible in patients under general anesthesia. Second, there might be a confounding effect of anesthetic agents on the association between VO2 and BT. The effects of sedative agents and neuromuscular blocking agents on VO2 could not be separated appropriately due to the lack of data in our study and the magnitudes of their effects on VO2 under general anesthesia are still uncertain [2 by hypothermia in this study [Our study is the first study to show an association between VOppressed –26. A prpatients . Furtherncertain , 28. Thuis study .2 between hyperthermia and normothermia but no significant difference in VO2 between hypothermia and normothermia in all categorized age groups, there was a significant difference in the association between VO2 and BT among the groups. Here, the differences in VO2 among different BT categories in pediatric patients, especially patients less than 1 year of age, deserve separate mentioning. Being different from the trend of VO2 in other age groups, the absolute change in VO2 for the change in BT was large and the relationship between VO2 and BT was close to linear in the whole range of BTs among patients less than 1 year of age. These findings suggest that neonates and infants, who have high VO2 as shown in previous studies and in our study, might have a large systemic organ response in VO2 to change in BT and have the possibility for further reduction in VO2 even at BT below normal BT [2 below normal BT might be due to small sample size and lack of power.Although our subgroup analyses among categorized age groups showed a significant difference in VOormal BT , 22. No 2 and protect systemic organs under the condition of inadequate oxygen delivery. For instance, hypothermia has been used to protect other organs such as the kidneys during cardiopulmonary bypass [2 for protecting organs. However, our results suggesting that VO2 is not reduced by hypothermia in adult patients might not be applicable to pediatric patients.Many strategies related to BT have been applied for patients with the belief that lower BT would decrease VOy bypass –11. Howey bypass –32. Our 2 measurements are issues. We used VO2 measurements based on Sykes’ formula, which might be affected by the percentage of dead space [2 measurement using Sykes’ formula is a good indicator of whether VO2 is rising or falling [2 minute-by-minute and calculating the mean of VO2 in every range of BTs in each patient in this study would also have contributed to improvement in precision due to variance of the monitoring system. Thus, our assessment of VO2 compared with BT, especially the relative trend in VO2 with change in BT, would be acceptable. Second, the association between VO2 and BT would not indicate robust causal inference. We performed linear mixed effects models with adjustment for age and gender, and the results showed a significant association between VO2 and BT. However, since it is known that general anesthesia with sedation and neuromuscular blockade decrease VO2 and that thermoregulation is impaired during general anesthesia, anesthetic agents and the level of anesthesia might confound the association [2 makes it difficult to estimate the effect of BT on VO2 [2 and BT.There are several limitations in this study. First, the accuracy and precision of the VOad space  and the ad space , 19. If  falling . Recordiociation –26, 33. T on VO2 , 28. ThiT on VO2 . We excl2 increases in parallel with increase in body temperature in a hyperthermic state but remains constant in a hypothermic state. Neonates and infants, who have high VO2, might have a large systemic organ response in VO2 to change in BT and have the possibility for further reduction in VO2 even at BT below normal BT.VOAdditional file 1:  Figure S1. Association between oxygen consumption and body temperature in patients younger than one year old. Abbreviations:VO2, oxygenconsumption; Ref, reference; *, p< 0.05; **, p< 0.01; *** p< 0.001Additional file 2: Figure S2. Association between oxygen consumption and body temperature inpatients between one and fiveyears old. Abbreviations: VO2,oxygen consumption; Ref, reference; *, p< 0.05; **, p< 0.01; *** p< 0.001Additional file 3: Figure S3. Association between oxygen consumption and body temperature inpatients between five and 18years old. Abbreviations: VO2,oxygen consumption; Ref, reference; *, p< 0.05; **, p< 0.01; *** p< 0.001Additional file 4: Figure S4. Association between oxygen consumption and body temperature inpatients 18 years old or older. Abbreviations:VO2, oxygenconsumption; Ref, reference; *, p< 0.05; **, p< 0.01; *** p< 0.001Additional file 5: Table S1.


CMR activation timing at the LV pacing site predicted post-CRT LV functional improvement (p < 0.05), and mechanical activation onset < 34 ms by CMR at the LVP site was associated with decreased post-CRT survival in a model with higher pre-CRT creatinine and B-type natriuretic peptide ; however, only the higher pre-CRT creatinine partially mediated (37%) the decreased survival in RVP-HF patients. In conclusion, RVP-HF had a distinct CMR phenotype, which has important implications for the selection of LV pacing sites in CRT upgrades, and only chronic kidney disease mediated the decreased survival after CRT in RVP-HF.As the mechanism for worse prognosis after cardiac resynchronization therapy (CRT) upgrades in heart failure patients with RVP dependence (RVP-HF) has clinical implications for patient selection and CRT implementation approaches, this study’s objective was to evaluate prognostic implications of cardiac magnetic resonance (CMR) findings and clinical factors in 102 HF patients  with and without RVP dependence undergoing upgrade and de novo CRT implants. Compared with other CRT groups, RVP-HF patients had decreased survival ( Between 1993 and 2009, the number of patients implanted with permanent pacemakers increased by 55.6% in the United States, and 2.9 million patients overall received permanent pacemakers during this period ,18,19,20As most cardiac implantable electronic devices are now MR-conditional ,27, and 2 before CRT to have a gadolinium-based contrast agent (GBCA) for research CMR at our institution, and the GBCA was withheld in the case of a lower GFR at the time of the scan. Exclusion criteria included contraindications for MRI, persistent atrial fibrillation without third-degree AV block, and a PVC burden greater than 15%. Patients were enrolled between 2011 and 2021.This study was approved by the Institutional Review Board for Human Subjects Research at the University of Virginia and included the enrollment of patients in different cohorts. Inclusion criteria for Group 1 required that patients were undergoing a de novo CRT defibrillator (CRT-D), and inclusion criteria for CRT upgrade patients required that they were undergoing an upgrade to a CRT defibrillator system with a coronary venous LV pacing lead for either RVP-HF (Group 2) or another accepted indication (Group 3). Other inclusion criteria for all patients were that they met published criteria for CRT  and werePrior to CRT device implantation, clinical characteristics for all patients were collected through intake forms and cross-referenced with electronic health records. These included demographics, medications, comorbid conditions, the QRS duration from the 12-lead electrocardiogram, and relevant laboratory findings, as described in Before the CRT procedure, patients underwent cardiac magnetic resonance (CMR) on a 1.5 T scanner. The MRI protocol included cine imaging, late gadolinium enhancement for myocardial scar detection, and strain imaging with displacement encoding with stimulated echoes (DENSE). Late gadolinium enhancement (LGE) was performed ten minutes after the injection of 0.1 mmol/kg of gadoterate meglumine (Dotarem), and a wideband pulse (bandwidth of 3.8 kHz) was added as needed  to minim2, and slice thickness of 8 mm. Displacement was encoded in two orthogonal directions, and a spiral k-space trajectory was used with 6 interleaves per image. Other parameters included: field of view = 350 × 350 mm2, displacement encoding frequency ke = 0.1 cycles/mm, flip angle = 15°, and echo time = 1.9 ms. DENSE images were analyzed using custom software. In a small number of patients in whom off-resonance artifacts were present on DENSE imaging, circumferential strain (Ecc) was derived using a convolutional neural network (Strain-Net) designed by our group to predict regional strain from cine imaging and validated in a recently published study demonstrating more accurate regional strain assessments compared with commercially available feature tracking [Regional circumferential strain was acquired using cine DENSE  in shorttracking .cc as previously reported [cc matrix [cc based on cardiac segment and phase, and an active contour guided by the Ecc gradient was used to automatically detect the mechanical activation time field, which was defined as the time to the onset of circumferential shortening [cc curve, as a negative slope of the Ecc curve indicates myocardial shortening. In order to calculate mechanical activation at the left ventricular pacing (LVP) site, the lead location was mapped to an LV segment (American Heart Association 17-segment model) based on procedural fluoroscopy using previously described methods [The CURE-SVD, a robust and validated mechanical dyssynchrony parameter  was derived from Ereported ,38. Regic matrix ,37,38. T methods ,39,40,41Post-CRT − LVESVIPre-CRT)/LVESVIPre-CRT; negative values are favorable, and −0.15 is often used as a cutoff for response in the literature when there is a need to convert the LVESVI-FC to a binary response indicator [2 before and after CRT, and measurements of BNP were used to consider the neurohormonal axis in CRT response.Echocardiography was used to calculate the fractional change in left ventricular end-systolic volume index (LVESVI-FC) as:  was performed using the glmnet package to identify the predictors of survival. The tuning parameter λ was used based on expert recommendations [p-values were reported.All statistical analyses were performed using R and Python. Statistical tests were performed to identify differences in baseline characteristics between the three upgrade/de novo CRT groups. Kruskal–Wallis tests were used to compare continuous variables, as not all data were normally distributed, and Dunn’s post hoc nonparametric test was used for pairwise comparisons. Chi-square tests and Fisher’s exact tests were used to compare differences in discrete variables. Reverse Kaplan–Meier curves stratified by cohort group were constructed, and the log-rank ndations  to elimiMediation analysis was performed to determine the extent to which the effect of an independent variable (the device group in this study) was mediated by predictors such as impaired renal function. The proposed mediator (creatinine) was regressed on the independent variable using linear regression, and survival/survival time was regressed on the mediator using a parametric survival model with a Gaussian distribution. The average causal mediation effect (ACME) was determined as the product of the regression coefficient for the effect of the independent variable on the mediator in the linear regression model and the regression coefficient for the effect of the mediator on survival time in 1000 bootstrapped samples. The method then facilitated the calculation of 95% confidence intervals for the mediator effect. This mediator effect was compared with the effect of the independent variable on survival/survival time.The baseline characteristics for the 102 patients  are shown in p = 0.03), had a higher frequency of atrial fibrillation (p = 0.0006), had greater pre-CRT QRS durations (p = 0.002), and had higher creatinine values (p = 0.002). BNP values were not significantly different across groups, although there was a trend for greater BNP in Group 2 vs. Group 1 (During a median follow-up of 4.8 years (IQR 4.2 to 5.0 years), 26 (25.5%) patients died. The 4-year death rate was 18.7% (19/102). Group 2 patients were older ( Group 1 .p = 0.0005), a smaller baseline LVEDVI (p = 0.0002), and greater LVEF (p = 0.06)  .p = 0.31 vs. Group 1 and p = 0.80 vs. Group 3).  As shown in p = 0.0002) with a similar distribution of LV free wall scar .The proportion with the favorable finding of mechanical activation greater than 34 ms at the LVP site was similar in all three groups (p = 0.020) after adjustment for CURE-SVD (p = 0.0085), which was also a significant predictor of this short-term outcome. LV free wall scar with LGE was associated with this response indicator alone (p = 0.057), but not after adjustment for either the Q-LV, the CURE-SVD, or both. For the outcome of improvement (lowering) in BNP post-CRT with adjustment for the pre-CRT value, both CURE-SVD (p = 0.037) and mechanical activation ≥ 34 ms at the LV lead implant site (p = 0.042) were significant predictors in a multivariable linear regression model. Both the Q-LV (p = 0.043) and CMR mechanical activation (p = 0.0039) were independently associated with survival time after CRT in a multivariable Cox proportional hazards regression model; however, only the mechanical activation predictor was associated with survival time after CRT after adjustment for pre-CRT BNP. Lead placement in anterior, anterolateral, posterolateral, or mid-apical-lateral AHA segments did not have an additional association in any of these models. No interactions with group assignments were noted in any of the models.In separate linear regression models in the combined cohort of de novo CRT and CRT upgrade patients, a longer Q-LV time was associated with a greater improvement in the LVESVI after CRT (p = 0.023) (p = 0.006), six-month BNP post-CRT (p = 0.002), and six-month change in peak VO2 post-CRT (p = 0.02) were associated with long-term survival after adjustment for CRT group .In a Cox proportional hazards model, Group 2 patients had worse survival compared with Group 1 patients  A but sim= 0.023) B. Comparp = 0.32).A plot of the LASSO regression coefficient values as a function of the tuning parameter (λ) is shown in The cohort was then split into a 70% training set and a 30% test set, and a standard logistic regression model with these four covariates was derived in just the training set. Predictions from this model in the test set were compared with actual events, and the predictions had an accuracy of 93.3% for predicting 4-year survival in the test set.p < 0.0001)  A. The mo 0.0001) B.p < 0.0001). Baseline BNP (p = 0.012), CABG (p = 0.020), and CMR mechanical activation time ≥ 34 ms at the LV pacing site (p = 0.040) were also significant predictors in the model. Reverse Kaplan–Meier curves are shown in p = 0.0059).In a Cox proportional hazards model with 26 death events, the pre-CRT creatinine, the pre-CRT BNP, CABG history, and mechanical activation ≥ 34 ms were all associated with survival in the multivariable model . Creatinp = 0.034). As p = 0.008), and the bootstrapped confidence interval for the total effect was −3.85 to −0.25 (p = 0.034). There was a 37% mediation effect of creatinine for the RVP-HF group effect on survival time (−0.855/−2.302 = 0.371). Other candidate baseline characteristics and response measures did not have a significant average causal mediation effect.The effect of a CRT upgrade with RVP-HF relative to de novo CRT on the likelihood of survival was partially mediated by the pre-CRT creatinine. The regression coefficient for the total effect of the CRT upgrade with RVP-HF on survival time using parametric survival regression with a Gaussian distribution was −2.302  pacing site. These findings also present a roadmap to identify prognosis in patients with CRT upgrades, and a nomogram is provided for this purpose. Moreover, the worse survival in upgrade RVP-HF patients in this cohort was mediated significantly by a comorbid condition, specifically renal impairment, in the upgrade RVP-HF cohort. Other comorbid conditions more common in CRT upgrade patients for RVP-HF in this cohort, such as atrial fibrillation, were found not to mediate the decreased survival as impaired kidney function did.With respect to prognosis in CRT upgrades, prior studies have yielded partially conflicting results. While some studies found similar overall survival in de novo and upgrade CRT patients ,25, otheIt is remarkable that the Budapest Upgrade CRT randomized trial showed a clinical benefit for upgrades to CRT devices in patients with RV pacing dependence . The finWith respect to implant findings and prognosis, LV free wall sites having later mechanical and electrical activation timing represent the areas in the LV that are most dysfunctional and typically undergoing the most stretch in early systole, such that pacing these sites is likely to have the most beneficial effect on LV function. In this cohort, we found the electrical activation at LVP site, mechanical activation at the LVP site, and overall mechanical dyssynchrony based on the CURE-SVD mechanical dyssynchrony index were prognostically important across de novo CRT and upgrade groups. The finding that electrical and mechanical activation at the LVP site both contribute favorably to response and survival in this mixed cohort highlights the importance of achieving both late electrical and late mechanical activation to achieve optimal CRT response rates.Another remarkable finding in this cohort is the anterior shift in late-activated sites observed for CRT upgrade patients with RVP-HF. This can be understood intuitively by the fact the RV lead position is typically in the area of seven o’clock on the LV short-axis views, and the anterior LV at the one o’clock position is the most distant from the RV pacing lead along the circumference of LV short axis, thus representing the most late-activated site. This anterior shift in late activation in RVP-HF has important implications for the CRT implant procedure in patients with CRT upgrades with RV pacing in this area. Although the LV pacing site chosen was at the discretion of the operator in this study, and this study was not a prospective interventional trial of CMR guidance for the selection of the LVP site, the prognostic importance of mechanical and electrical late activation at the LVP site in this cohort suggests that CRT upgrade patients with RVP-HF may have better results if operators target more anterolateral sites, and more anterior sites may even be good pacing targets in this scenario. In many patients, the anterior or anterolateral LV may be easier to access from the coronary sinus and may be less likely to have phrenic nerve capture; however, operators implanting CRT in patients with LBBB typically strive to achieve a more posterolateral LV lead position if there is not scar in this area. Furthermore, sometimes coronary venous pacing options are limited, and an anterior lead position may be the only one that works.There were several limitations of this study. Although a cohort of 102 patients with curated CMR, clinical, laboratory, response, and survival data with a median follow-up over 4 years distributed over three groups is considered to be reasonably large and sufficient for the mechanistic study presented, a larger cohort would have facilitated additional approaches based on neural networks and other machine learning methods; however, it is reassuring that the main model had excellent accuracy in a test set when derived in a training set. Second, although patients were on maximally tolerated medical therapy appropriate at the time of enrollment, angiotensin-neprilysin inhibitors and sodium-glucose cotransporter-2 inhibitors have since become widely used medications for heart failure. While this is an inherent limitation for any long-term study because new medications may well be introduced during the five years of follow-up, the impact on the results of this study is likely very modest, as sodium-glucose cotransporter-2 inhibitors decrease heart failure and other cardiac events with minimal impact on survival , and heaIn conclusion, RVP-HF had a distinct CMR phenotype, which has important implications for the selection of LV pacing sites in CRT upgrades, and only chronic kidney disease mediated the decreased survival after CRT in RVP-HF.


During early systole, ischemic myocardium with reduced active force experiences early systolic lengthening (ESL). This study aimed to explore the diagnostic potential of myocardial ESL in suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients with normal wall motion and left ventricular ejection fraction (LVEF).Overall, 195 suspected NSTE-ACS patients with normal wall motion and LVEF, who underwent speckle tracking echocardiography (STE) before coronary angiography, were included in this study. Patients were stratified into the coronary artery disease (CAD) group when there was ≥ 50% stenosis in at least one major coronary artery. The CAD patients were further stratified into the significant (≥ 70% reduction of vessel diameter) stenosis group or the nonsignificant stenosis group. Myocardial strain parameters, including global longitudinal strain (GLS), duration of early systolic lengthening (DESL), early systolic index (ESI), and post-systolic index (PSI), were analyzed using STE and compared between groups. Receiver operating characteristic curve (ROC) analysis was performed to determine the diagnostic accuracy. Logistic regression analysis was conducted to establish the independent and incremental determinants for the presence of significant coronary stenosis.The DESL and ESI values were higher in patients with CAD than those without CAD. In addition, CAD patients with significant coronary stenosis had higher DESL and ESI than those without significant coronary stenosis. The ROC analysis revealed that ESI was superior to PSI for identifying patients with CAD, and further superior to GLS and PSI for predicting significant coronary stenosis. Moreover, ESI could independently and incrementally predict significant coronary stenosis in patients with CAD.The myocardial ESI is of great value for the diagnosis and risk stratification of clinically suspected NSTE-ACS patients with normal LVEF and wall motion.The online version contains supplementary material available at 10.1186/s12872-023-03364-y. Non-ST-segment elevation acute coronary syndrome (NSTE-ACS) accounts for more than 70% of acute coronary syndromes, and its incidence and mortality have been increasing for the past few decades . PatientIschemic myocardial fibers with a reduced active force may exhibit stretching instead of shortening when the LV pressure rises during early systole. This paradoxical myocardial stretch is defined as ESL  Fig. 1)1). Previ2). Written informed consent was obtained from each patient, and the institutional ethics committee approved the research protocol (No. 2021-department-395).In this single-center study, 272 clinically suspected NSTE-ACS patients referred to coronary angiography from February to July 2019 were retrospectively enrolled. STE was performed within one day of coronary angiography. The following inclusion criteria were applied: LVEF ≥ 55% and no regional wall motion abnormality on conventional echocardiography. The exclusion criteria were as follows: (i) previous myocardial infarction, and/or revascularization procedure or cardiac resynchronization therapy; (ii) moderate or severe valve disease; (iii) cardiomyopathy and congenital heart disease; (iv) left bundle branch block or atrial fibrillation; (v) suboptimal echo images or ≥ 1 unanalyzable segment in the STE analysis. A total of 195 patients were finally included in this study  with an S5-1 phased-array transducer. Briefly, three consecutive heart cycles were obtained by two-dimensional images, and the recordings were digitally stored and subsequently analyzed offline using the Philips Qlab software (ver. 13.0). All patients underwent echocardiography before the coronary angiography . The echocardiographic data were analyzed by researchers blinded to all clinical information.The conventional echocardiography was evaluated according to the recommendations provided by the American Society of Echocardiography guidelines at the resting state . The modTwo-dimensional echocardiographic images of the apical 2-, 3-, and 4-chambers were used to determine the LV longitudinal strain. The frame rate was set at 65 ± 7 frames/s. In each apical view, a region of interest was automatically traced by the software, with subsequent manual adjustment to ensure accurate tracking, if necessary. End-systole was defined as the time of aortic valve closure (AVC). From the STE curves, the following strain values were extracted in each segment: peak early systolic positive strain , peak systolic longitudinal strain (indicating maximum systolic shortening), and peak longitudinal strain (indicating maximum shortening in cardiac cycle). As a measure of global systolic function, the global longitudinal strain (GLS) was calculated by averaging the peak systolic strain values from an 18-segment model. The standard deviation of the time to peak systolic strain in 18 segments of the left ventricle represents the mechanical dispersion (MD). We defined the duration of ESL (DESL) as the time from end-diastole (peak R-wave of the electrocardiogram) to early systolic strain. We assessed the early systolic index (ESI) as [-100 × ]  group when there was ≥ 50% stenosis in at least one major coronary artery. No CAD was defined as the group with any main coronary stenosis < 50% or normal coronary arteries. Patients with CAD were further stratified into the significant (≥ 70% reduction of vessel diameter) stenosis group or the nonsignificant stenosis group. CAD patients were also grouped based on the number of significantly stenosed arteries. For patients with significant coronary stenosis, percutaneous coronary intervention (PCI) was performed based on the judgment of the operator.th–75th percentiles), depending on whether the data were normally distributed. Between-group comparisons were analyzed by the Student’s t–test, Mann–Whitney U test, analysis of variance, or Kruskal–Wallis test, with Bonferroni correction applied for post hoc tests as appropriate. Categorical variables were presented as numbers (percentages), and the chi-squared or Fisher’s exact test was performed to compare the differences between groups. Diagnostic accuracy was assessed by calculating the area under the receiver operating characteristic (ROC) curve (AUC). The comparison between AUCs was tested using the method of DeLong in MedCalc. Spearman’s rho was used to evaluate the correlation between the LV deformational parameters. Logistic regression analysis was conducted to determine the association between the baseline clinical characteristics, echocardiographic variables, and significant coronary stenosis in NSTE-ACS patients. In addition, the potential incremental values of the strain parameters in terms of diagnostic utility were assessed by comparing the AUCs of a series of prediction models. Intra-observer and inter-observer variabilities were assessed for the LV deformation parameters using intraclass correlation coefficients (ICCs). The analyses were performed by two independent observers in 10 randomly selected patients. A P-value of < 0.05 was considered statistically significant. The statistical analyses were performed using SPSS version 23.0  and MedCalc 15.6 .Continuous variables were expressed as the mean ± standard deviation or median (25n = 30) and CAD (n = 165). The patients with CAD were then subdivided into the significant stenosis group (n = 122) or the nonsignificant stenosis group (n = 43). The detailed baseline characteristics are summarized in Table P < 0.05). In the subgroups of CAD, the patients with significant coronary stenosis had a higher prevalence of diabetes mellitus and higher levels of troponin I compared with those in the nonsignificant stenosis group (P < 0.05). There were no signifcant differences in the other clinical characteristics among the no CAD group, nonsignificant stenosis group and significant stenosis group.A total of 195 patients with suspected NSTE-ACS  were included in the present study. Based on the coronary angiographic findings, all patients were initially divided into two groups: no CAD (P < 0.05). Compared to the patients without CAD, those with CAD had lower absolute GLS (P < 0.05) values and higher DESL, ESI, and PSI values (P < 0.05). Notably, the patients in the significant stenosis group had markedly higher DESL, ESI, and PSI values as well as impaired GLS compared to the subjects in the other two groups (P < 0.05). The values of all strain parameters followed the trend of the no CAD group, the nonsignificant stenosis group, and the significant stenosis group. Comparisons among patients with CAD according to the number of significantly stenosed coronary arteries are shown in Supplemental Table P < 0.05, Supplemental Table The comparisons of the conventional echocardiographic findings and the global LV myocardial deformation parameters are presented in Table P < 0.05); Table P < 0.05) and PSI  in discriminating between significant and nonsignificant coronary stenosis in patients with CAD, providing a sensitivity of 62% and a specificity of 88% . As shown in Fig. χ2 = 26.2 vs. 4.7, P = 0.001). Furthermore, the predictive efficacy of model 2 (model 1 plus PSI) was significantly improved by adding ESI (model 3), with an increase in χ2 value from 26.2 to 49.3 (P = 0.002).Table The ICCs of inter- and intra-observer variability were 0.83 and 0.95 for GLS, and 0.62 and 0.85 for PSI, respectively. Furthermore, moderate reproducibility for DESL  and ESI  were identified in the present study  DESL and ESI were higher in the patients with CAD than in those without CAD; furthermore, the patients in the significant stenosis group had higher DESL and ESI values than those in the nonsignificant coronary group. (ii) ESI was superior to PSI for identifying patients with CAD, and it was further superior to GLS and PSI for predicting the presence of significant coronary stenosis. (iii) ESI could provide independent and incremental value for predicting significant coronary stenosis in patients with CAD. These results suggest that myocardial ESL may be valuable for the diagnosis and risk stratification of clinically suspected NSTE-ACS patients with normal LVEF and wall motion. A previous study has confirmed that up to one-third of suspected NSTE-ACS patients may not need coronary angiography . In patiThe present study revealed that DESL and ESI were higher in patients with CAD compared to those without CAD. Furthermore, patients in the significant stenosis group had higher ESL values compared to those in the nonsignificant stenosis group. These findings suggest that myocardial ESL can be used to detect minor LV systolic dysfunction earlier than the LVEF and wall motion visual evaluation. Consistent with Weng et al. , there wP < 0.05) for predicting significant coronary stenosis. The different capacity of GLS to diagnose CAD may be due to the less severe myocardial damage in the CAD patients with normal LVEF and wall motion in our study. Even in this situation, ESI still had excellent diagnostic performance, assumingly because the calculation of ESI integrated both peak early systolic positive strain and peak longitudinal strain in the cardiac cycle equally. Several reasons may contribute to this result. First, GLS reflects only the average level of the peak systolic longitudinal strain, while ESI integrates both the early systolic peak positive strain and the peak systolic longitudinal strain. In addition, GLS cannot fully reflect mechanical systolic motion, and the coordination of the LV systolic motion can be analyzed by ESL. Therefore, ESI was a more reliable marker of myocardial function in suspected NSTE-ACS patients with normal LVEF and wall motion.Caspar et al.  found thSome researchers have suggested that PSS, a delayed myocardial contraction after end-systole, is equal or more important than the commonly used LV strain in patients with CAD , 31. ConHowever, the cut-off values for ESL-related indices should be interpreted with caution, since the values in our study were markedly lower than those from a previous study . We consOur study had some limitations that must be addressed. First, this was a retrospective study with a relatively small number of subjects; thus, large-scale and prospective studies are needed to confirm these results. Second, the radial and circumferential strains were not analyzed because longitudinal mechanics were sensitive markers of cardiovascular disease . HoweverThe myocardial ESI could identify patients with CAD suspected of having NSTE-ACS and further accurately predict the presence of significant coronary stenosis. In addition, this index provided an independent and incremental predictive ability for significant coronary stenosis in patients with CAD. Therefore, the myocardial ESI may be a potentially valuable tool for the diagnosis and risk stratification of suspected NSTE-ACS patients without wall motion or LVEF abnormality.Additional file 1: Supplemental Fig 1. Flowchart of the study population.Additional file 2. Supplemental Table 1. Echocardiographic data according to the extent of CAD.Additional file 3. Supplemental Table 2. Spearman’s correlations between myocardial deformational parameters.Additional file 4. Supplemental Table 3. ROC curve results to predict significant coronary branch stenosis.Additional file 5. Supplemental Table 4. Interobserver and intraobserver variability (ICCs).


Pituitary adenoma (PA) is a type of tumor that develops in the sella turcica and is one of the most frequent intracranial tumors. It belongs to a type of adenoma derived from a single clone of cells in the pituitary gland. PA ranks third among all intracranial tumors, following only gliomas and meningioma. The average prevalence rate is approximately 15% at autopsy and 22.5% at radiological examinations.Most PAs are benign and non‐invasive adenomas that can be removed surgically or controlled with medication. However, approximately 35% of them show invasion into nearby anatomical structures and cannot be completely resected. 0.1%~0.2% of PA cases eventually develop into pituitary carcinomas. Additionally, PA may cause severe morbidity due to mass effects and the disorder of pituitary hormone secretion. Therefore, there is an urgent need to clarify the pathological mechanism of PA, improve the accuracy of diagnosis, and develop targeted therapies.Although current knowledge about the pathogenesis of PA remains limited, epigenetic modulation of PA has been increasingly implicated. Long non‐coding RNAs (lncRNAs) are known to regulate gene expression post‐transcriptionally and exert substantial roles in the initiation, progression, or suppression of various tumors. Accumulating evidence has shown close relationships between lncRNA dysregulation and PA development.This review highlights recent progress in the study of lncRNAs in PA pathogenesis and their potential as diagnostic/prognostic biomarkers or therapeutic targets for PA patients. They are over 200 nucleotides in length and have epigenetic regulatory potential.2PA is a type of benign epithelial tumor that arises from the anterior pituitary gland. It can be classified according to different criteria.Currently, several therapeutic options are available for PA, including surgery, radiotherapy, chemotherapy, immunotherapy, as well as the emerging molecular‐targeted therapy.33.1LncRNAs represent a class of RNA transcripts with lengths over 200 nucleotides. They display higher spatial and temporal specificity and lower conservation compared to mRNAs.Recently, more and more evidence has described the aberrant expression of multiple lncRNAs being involved in the occurrence and progression of PA. For example, lncRNA CCAT2 was dramatically induced in PA tissues and correlated with the poor prognosis in PA patients. Further loss‐of‐function and gain‐of‐function experiments found that CCAT2 positively modulated the proliferation, migration, and invasion of PA cells, and displayed an oncogenic property in PA carcinogenesis and progression.3.2IPA is characterized by exuberant cell proliferation, which is an important indicator for measuring the invasiveness of PA.3.3IPA cells possess high aggressive characteristics and can invade and damage adjacent tissues, including the sellar area and cavernous sinus.3.4EMT is a process whereby polarized epithelial cells are transformed into mesenchymal cells and display attenuated cell adhesion, enhanced motility, and invasive properties.3.5IPA cells are inclined to undergo glycolysis preferentially to adapt to changes in the surrounding environment under aerobic conditions, which is known as the “Warburg effect.”44.14.1.1The major difficulty in defining a PA as aggressive is the absence of predictive biomarkers. A recent microarray analysis revealed the expression patterns of lncRNAs in IPA, and identified 81 upregulated lncRNAs and 165 downregulated lncRNAs in IPA compared to NIPA.4.1.2Recurrence is an important factor in refractory PA.In recent years, ncRNAs, including lncRNAs, have emerged as novel prognostic biomarkers for predicting the recurrence of PA. For example, lncRNA H19 has been considered as an oncogene in a variety of tumor cells. The expression of plasma exosome‐derived H19 was frequently downregulated in human primary PA and negatively correlated with tumor growth by restraining 4E‐BP1 phosphorylation.4.2The ceRNA hypothesis has revealed a new mechanism for the interactions between RNAs.Certain differentially expressed lncRNAs are abnormally regulated in IPA tissues and cells, these lncRNAs are shown to participate in cell viability, proliferation, migration, invasion, and EMT by sponging corresponding miRNAs. For example, the SNHG6/miR‐994/RAB11A axis exerted crucial roles in modulating proliferation, migration, invasion, and EMT progress in HP75 cells, indicating SNHG6 and miR‐994 might serve as valuable therapeutic targets for IPA.5Although most PA patients generally have a good prognosis, a certain proportion of them will experience recurrent or progressive PAs characterized by invasion, rapid growth, high recurrence, and poor response to standard treatment. The difficulties that need to be urgently resolved in the diagnosis and treatment of refractory PA include: identifying early biomarkers of refractory PA, determining biomarkers for treatment response, and explicating the combination and sequence of different treatment regimens. The early identification and intervention of refractory PA is difficult and needs to be managed by a multidisciplinary team of experts. For patients suspected of having refractory PA, it is necessary to comprehensively examine and evaluate the imaging, biochemical, and histopathological findings. Currently, temozolomide has been widely used as the first‐line chemotherapy drug for refractory PA; however, its efficacy is usually limited.Emerging therapeutic strategies are providing alternative options for refractory PA. LncRNAs exert important regulatory functions in the pathogenesis of diverse tumors by promoting cell proliferation, differentiation, migration, invasion, and apoptosis at transcriptional, translational, and posttranslational levels, representing a new class of molecular targets for tumor treatment, including PA. Additionally, circulating lncRNAs could serve as novel biomarkers for early diagnosis and prognosis of PA. Further study of the roles and mechanisms of the reported lncRNAs in PA proliferation and invasion, in particular the mechanisms of lncRNA‐mediated resistance of PA cells to chemotherapy drugs, will shed light on the treatment of refractory PA. In addition, in view of the large number of lncRNAs in humans, and the fact that only a few of them have been functionally studied, it is urgent to develop efficient tools to identify new critical lncRNAs and to explore their roles and mechanisms in the pathogenesis of PA. Furthermore, most of the relevant studies are small case reports, further basic and clinical studies are needed to explore the efficacy and feasibility of novel therapies in refractory PA.All authors have written, revised, and approved the manuscript.The authors declare no conflict of interest.


The role of myocardial strain in risk prediction for acute myocarditis (AMC) patients, measured by cardiac magnetic resonance (CMR), deserves further investigation. Our objective was to evaluate the association between myocardial strain measured by CMR and clinical events in AMC patients.This was a prospective single-center study of patients with AMC. We included 100 patients with AMC with CMR confirmation. The primary outcome was the composite of all-cause mortality, heart failure and AMC recurrence in 24 months. A subgroup analysis was performed on a sample of 36 patients who underwent a second CMR between 6 and 18 months. The association between strain measures and clinical events or an increase in left ventricular ejection fraction (LVEF) was explored using Cox regression analysis. Global peak radial, circumferential and longitudinal strain in the left and right ventricles was assessed. ROC curve analysis was performed to identify cutoff points for clinical event prediction.p = 0.012), LV circumferential strain  and LV longitudinal strain  were independently associated with clinical event occurrence. The areas under the ROC curve for clinical event prediction were 0.80, 0.79 and 0.80 for LV radial, circumferential, and longitudinal strain, respectively. LV longitudinal strain was independently correlated with prognosis , even when analyzed together with ejection fraction and delayed enhancement. LV and right ventricle (RV) strain were not associated with an increase in LVEF. Finally, when the initial CMR findings were compared with the follow-up CMR findings, improvements in the measures of LV and RV myocardial strain were observed.The mean follow-up was 18.7 ± 2.3 months, and the composite primary outcome occurred in 26 patients. The median LVEF at CMR at baseline was 57.5% (14.6%). LV radial strain (HR = 0.918, 95% CI: 0.858–0.982, Measurement of myocardial strain by CMR can provide prognostic information on AMC patients. LV radial, circumferential and longitudinal strain were associated with long-term clinical events in these patients. Most patients with acute myocarditis (AMC) should be treated conservatively. The use of standard heart failure (HF) therapies such as diuretics, vasodilators, beta-blockers and aldosterone antagonists is indicated only in cases with reduced ejection fraction. When cardiogenic shock is present, the use of inotropes, intravenous vasodilators and circulatory assist devices may be needed, and progressive improvement is usually seen –5. The iThe use of cardiac magnetic resonance (CMR) has increased the confirmation rates of AMC by detecting hypersignals in T2 (inflammation marker) and late gadolinium enhancement imaging . The diaIn recent years, efforts have been made to identify CMR findings correlated with prognosis in patients with AMC –15. Howe2, creatinine clearance <30 ml/min (Cockcroft and Gault), a known gadolinium allergy and claustrophobia. Our institutional review board for human subject studies approved this study, and all participants provided written informed consent prior to enrollment. A subgroup analysis was performed with a sample of patients who underwent a second CMR between 6 and 18 months after the initial episode of AMC. High-sensitivity cardiac troponin I was measured by the commercial ADVIA Centaur® TnI-Ultra kit . The 99th-percentile value was 40 ng/L.The study design is presented in Vantage/Titan, Toshiba Medical Systems, Otawara, Japan). Images were acquired and coupled to the ECG during breath-hold in the four-chamber, short-axis and long-axis views of the left ventricle (LV) in the exact same location in different sequences. This allowed a precise comparison between cardiac function and regional myocardial structure. The parameters used in the dynamic sequences were a repetition time (RT) of 3.5 ms, echo time (ET) of 1.5 ms, flip angle of 60°, receiver bandwidth of ±125 kHz, field of view (FOV) of 35 cm × 35 cm, matrix of 256 × 148, temporal resolution of 35 ms, and slice thickness of 8.0 mm, without a gap between the slices.All patients underwent a brief interview prior to the CMR test, which covered height, weight, medical history and previous exams. CMR exams were performed on all patients with a scanner of 1.5 T  (dark blood) and long echo time , with breath-hold, in short-axis view of the LV. The images were positioned carefully to guarantee the presence of adequate skeletal muscle for reference. In this sequence, we used volumetric body coil acquisition to guarantee volume homogeneity and avoid signal loss, as usually occurs with surface coils. The parameters evaluated were an RT of 2× the RR interval, an ET of 80–120 ms, an echo train length of 24 (ETL), an inversion time (IT) of 140 ms, a slice thickness of 10 mm, a gap of 2 mm, a field of view of 34 cm × 38 cm, and a matrix of 256 × 256. We applied a spin‒echo free breathing sequence in the axial plane tipped inferiorly toward the left to align with the inferior wall of the left ventricle, with no change in acquisition parameters from before to immediately after intravenous injection of 0.2 mmol/kg gadolinium contrast agent  at a 3 ml/s rate, which was followed by 30 ml of saline. The sequence began immediately after injection and lasted 3–4 min; the images reflected gadolinium enhancement for an average time of 2 min. The sequence parameters were as follows: field of view adjusted to include the left upper arm, echo train length of 2–4, slice thickness of 8–10 mm, 128 The myocardial late enhancement technique was used to investigate myocardial fibrosis. An inversion-recovery prepared gradient-echo was acquired 10–20 min after the contrast was used, with the following parameters: RT, 7.1 ms; ET, 3.1 ms; flip angle, 20°; cardiac phases, 1; views per segment, 16–32; matrix, 256 × 192; slice thickness, 8 mm; gap between slices, 2 mm; field of view, 32–38 cm; inversion time, 150–250 ms; receiver bandwidth, 31.25 kHz; number of excitations, 2; and acquisition every heart beat. Additionally, we performed a sequence as described above but with a TI of 600 ms for further characterization of cardiac thrombus.The late gadolinium enhancement area was calculated using a threshold technique with a threshold value of 2 standard deviations using cvi software. That is, all myocardial pixels with an enhancement 2 standard deviations above the mean of the normal myocardium were considered to have late enhancement. We delimited the endocardium and epicardium manually so that the software did the calculations only in the myocardium and excluded any evident visual artifacts or pixels that may be external to the myocardium .Circle Cardiovascular Imaging, Inc., Calgary, Canada). The global radial, circumferential and longitudinal peak strains of the LV and right ventricle (RV) were acquired through the short-axis view across 4 chambers and 3 chambers. In the tissue tracking analysis, the endocardial and epicardial borders were manually contoured at the end of diastole. The parameters were automatically calculated by the software. In the subgroup of patients undergoing a second CMR, the same methodology described above was used. In all measurements, global strain was used. For the longitudinal strain, the long axis (LAX slices) was used. For the radial and circumferential strain, the short axis (SAX slices) was used. The same measurements were performed in the right and left ventricles. In the right ventricle, measurements were performed with greater caution due to the lower thickness of the ventricle wall. Examples of the strain measures are shown in Myocardial strain analyses were performed using cvi 42 software version 5.13.5  between the variable and the occurrence of clinical events in the univariate analysis. The following baseline characteristics were considered as variables in the analysis because they were significantly different between the groups: age, sex, diabetes mellitus, systemic arterial hypertension, dyslipidemia, smoking, creatinine and medications used at hospital discharge.The associations between CMR peak strain in the radial, circumferential and longitudinal axes in the LV and RV and the occurrence of clinical events were explored. Additionally, the association between CMR peak strain and changes in LVEF was described. Multivariate analysis was performed by Cox regression analysis only when there was a significant association  curves was also performed to identify the cutoff points with the highest discrimination for clinical event prediction. The 95% confidence intervals (CIs) of the cutoff points are shown. For direct comparisons of continuous variables in the initial vs. follow-up CMR, the Wilcoxon test was used. Data were analyzed with SAS Statview 5.0 software.A total of 102 patients presenting with chest pain and a final diagnosis of AMC confirmed by CMR were included between March 2013 and June 2018 at the Emergency Department of the Heart Institute, InCor, University of Sao Paulo Medical School, Sao Paulo, Brazil. Two patients were lost to follow-up during the study period. The mean follow-up was 18.7 ± 2.3 months. The final analysis included the remaining 100 patients. The baseline characteristics are presented for the overall population and stratified by the occurrence of clinical events in There were 2 deaths during follow-up. HF events were observed in 20 patients, and AMC recurrence was observed in 17 patients. The composite primary outcome occurred in 26 patients.p = 0.012), LV circumferential strain  and LV longitudinal strain  remained associated with clinical events.The results of the univariate analysis are presented in The cutoff points with the highest discrimination for clinical event prediction were 19.9% for LV radial strain, −14.5% for LV circumferential strain, and −12.3% for LV longitudinal strain. The areas under the ROC curve for clinical event prediction were 0.80 for LV radial strain, 0.79 for LV circumferential strain, and 0.80 for LV longitudinal strain .p = 0.007), while ejection fraction  and late gadolinium enhancement area  did not show a positive result.A multivariate analysis was performed to find the independent variables from among LV longitudinal strain, left ventricular ejection fraction and late gadolinium enhancement area. The only variable that maintained correlation with long-term combined events was LV longitudinal strain . CMR-based diagnosis of myocarditis has evolved since the original enrollment of patients. The LGE area was calculated with 2 SD, which in a way may overestimate the impairment. In patients in whom edema was not visualized in the CMR, no diagnostic auxiliary imaging method or endomyocardial biopsy was performed. Finally, different treatments were administered to patients with AMC during the study period, which could have influenced the results. Further studies with larger sample sizes may further validate our findings.In conclusion, measures of myocardial strain obtained by CMR can provide prognostic information in patients with AMC. LV radial, circumferential and longitudinal strain were associated with long-term clinical events in these patients. Although LGE had not shown a predicted value for event over the strain in our manuscript, additional studies are needed to better understand LGE predicted value in this scenario.


Cardiac magnetic resonance (CMR) has been recently implemented in clinical practice to refine the daunting task of establishing the risk of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). We present an exemplificative case highlighting the practical clinical utility of this imaging modality in a 24-year-old man newly diagnosed with an apical HCM. CMR was essential in unmasking a high risk of SCD, which appeared low-intermediate after traditional risk assessment. A discussion examines the essential role of CMR in guiding the patient’s therapy and underlines the added value of CMR, including novel and potential CMR parameters, compared to traditional imaging assessment for SCD risk stratification. Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease  and is characterized by an increased left ventricular (LV) wall thickness in the absence of abnormal loading conditions , some HCA 24-year-old man underwent a cardiological visit because of exertional dyspnea. He rarely engaged in sports, but for four months, he had noted sporadic shortness of breath during ordinary efforts with mild limitation of his physical activity in the absence of chest pain, palpitations, or syncope. His past medical history was non-significant. The patient denied cardiovascular risk factors or a family history of SCD or cardiomyopathy. His blood pressure was 120/80 mmHg, and his heart rate was 70 bpm. His physical examination was within normal limits. A 12-lead ECG showed sinus rhythm, normal atrioventricular conduction, LV hypertrophy, and inverted T waves in all leads but aVR, D3, and V1 A.2) were observed. There was also right ventricular (RV) hypertrophy, with a maximum RV wall thickness equal to 8 mm. The conventional indices of RV systolic function were normal  showed an “ace of spades” LV morphology with apical hypertrophy  with preserved pump function  66%, The 48 h Holter EKG monitoring showed normal sinus rhythm, no sustained or non-sustained ventricular arrhythmias, with a premature ventricular complex burden <5%. Laboratory examinations revealed mildly increased high-sensitivity troponin I  and BNP .Genetic testing showed a class IV variant (likely pathogenetic) in the MYBPC3 gene (c.482dupC), causing a premature stop codon to form.After a multidisciplinary meeting, the patient underwent a subcutaneous ICD (s-ICD) implantation for primary prevention. He was also advised against participation in competitive sports and discouraged from intense physical activity. The patient was started on bisoprolol, up to 3.75 mg daily, with improvement of his dyspnea (NYHA I-II) at the 9-month follow-up, with no arrhythmic events at device interrogation. The beta-blocker was not further up-titrated due to bradycardia.Identifying the subgroup of HCM patients at risk of SCD is daunting for physicians in daily practice . TraditiThe present case is emblematic and exemplificative in underlying the added role of CMR in SCD risk stratification in patients with HCM, especially in those at low-intermediate risk for SCD on traditional assessment. Such HCM patients, including the one reported in the present manuscript, would not be captured at significant risk of SCD and would remain unprotected from SCD based only on echocardiographic imaging assessment. In these cases, the addition of CMR allows the physicians to refine SCD risk, leading to a dramatic impact on clinical decision-making , thanks to the high accuracy of CMR in measuring imaging parameters that are also detectable at echocardiography, together with the unique capability of the method to unveil the burden of myocardial fibrosis, which is growlingly recognized an essential risk factor for malignant ventricular arrhythmias.Thus, CMR has recently been upgraded for SCD risk stratification in the latest international guidelines. This examination is initially indicated for patients with HCM who are not otherwise identified as high risk for SCD or whose ICD implant remains uncertain after conventional clinical and echocardiographic assessment. Follow-up CMR (every three to five years) is also indicated for non-high-risk HCM patients to update SCD risk stratification in parallel with potential changes regarding LGE, LVEF, maximum left ventricular wall thickness (MLVWT), and the development of apical aneurysms .Based on traditional risk assessment, the ESC HCM SCD risk score  entailedEstablished and promising imaging parameters useful for SCD risk stratification are reported in The European and American guidelines contemplate the following parameters detectable by CMR for SCD risk stratification in HCM patients: LVEF, MLVWT, LA size (expressed as anteroposterior diameter), the presence of an apical aneurysm and LGE (expressed as a percentage of LV mass) ,12. For CMR is more accurate and sensitive than echocardiography in assessing LV wall thickness. Accordingly, CMR can unmask hypertrophic segments that are missed by echocardiography. Maron et al.  found thConversely, the reduced accuracy of echocardiography compared to CMR might also result in an overestimation of LV wall thickness. In a cohort of 195 HCM patients , the oveMLVWT as a prognostic marker is subject to considerable intra- and inter-reader variability, even when image quality and operator experience is high, resulting in inappropriate decisions concerning ICD implantation potentially being made in one in seven patients, as demonstrated by Captur et al. . CompariA unique advantage of CMR compared to echocardiography is the capability to detect myocardial fibrosis through LGE, which has been associated with an increased risk of SCD in several non-ischemic cardiomyopathies ,24,25,26More than half of HCM patients exhibit LGE, most commonly involving hypertrophied segments of the LV ,10, and p = 0.002) and LGE ≥ 15% of LV mass demonstrated a two-fold increase in SCD event risk in those patients otherwise considered at lower risk, with a rate of SCD of 6% at five years. On the other hand, the absence of LGE reduced the risk of SCD . Especially in low-mid risk patients, as per conventional criteria, CMR can correctly re-classify their future risk of potentially lethal ventricular arrhythmias and allow timely implantation of an ICD in primary prevention. The prognostic value of LGE in HCM patients has been confirmed in a meta-analysis including almost 3000 patients, where both the presence and extent of LGE were associated with SCD and all-cause mortality, among others, independently of baseline characteristics; in particular, the adjusted HR was 1.36 per 10% of LGE  [A seminal study by Chan et al.  found a A study by Weissler-Snir et al.  found thConventionally, an LGE cutoff ≥15% of LV mass is considered a risk factor for SCD ,12. HoweAlthough the process of LGE quantification has been subject to methodological discrepancies among different centers, semi-automated algorithms, including myocardial regions with a signal intensity five standard deviations higher than the remote myocardium after contrast injection, are commonly used in everyday practice .Evaluation of the pattern of LGE at CMR is also key in the diagnostic process, especially in the differential diagnosis of other cardiomyopathies where hypertrophy is present such as cardiac amyloidosis, where global subendocardial or transmural LGE is frequently observed , and FabCMR has shown superior sensitivity in detecting LV apical aneurysms/apical thinning compared to echocardiography, whose sensibility is less than 70%, especially for small aneurysms (defined as <20 mm) ; howeverThe asymmetric hypertrophy of HCM patients renders Simpson’s biplane method of discs inaccurate, given that this echocardiographic approach makes incorrect geometric assumptions about regular and symmetric LV orientation and cross-sectional shape. Accordingly, CMR has shown superior reproducibility compared to echocardiography when assessing LV dimensions and function. Grothues et al. , in a coLeft atrium size, expressed as anteroposterior diameter, is considered in the ESC HCM risk score. As of today, LA volume is the preferred method to quantify LA sizes, given that LA diameter is not a reliable size marker in patients with asymmetrical enlargement of the LA . CMR is Although LGE evaluation is the reference standard for in vivo assessment of myocardial scar, depicting the relative difference between enhancing areas of fibrosis and normal myocardium, diffuse fibrosis can go undetected on LGE maps because of the absence of normal reference myocardium and because identification of microscopic interstitial fibrosis is limited by the spatial resolution of LGE images . Quantitp < 0.001), maintaining the association  in a subgroup of patients judged low risk as per European and American guidelines [A recent longitudinal study including 203 HCM patients found that, at multivariate analysis, native T1 by CMR was associated with a combined clinical endpoint including cardiac death, transplantation, heart failure admission, and ICD implantation  fraction, derived from the myocardium and blood T1 values before and after gadolinium administration as well as the patient’s hematocrit, reflects the excess collagen deposition in the extracellular space. A recent study with a small sample size demonstrated that ECV was the best CMR parameter to identify patients with HCM-SCD risk ≥ 4% . AnotherRV hypertrophy can be identified in 31–44% ,48 of HCRV-LGE might be challenging to assess, given the thin-walled structure of the RV. As of today, there is no link between RV-LGE and SCD in HCM patients. Overall, the clinical implications of RV involvement by CMR on the risk of SCD remain undefined.p < 0.001) after adjusting for conventional clinical characteristics, echocardiography, and CMR parameters, showing incremental prognostic value over conventional variables [p = 0.043) [Feature tracking CMR is a promising tool for detecting systolic functional abnormalities occurring earlier than LVEF impairment . In a reariables . In anot= 0.043) . Larger 2 = 0.38; p < 0.001) [As mentioned above, LV hypertrophy has been mainly evaluated by measuring MLVWT. However, hypertrophy can be asymmetrically distributed in HCM patients, and genotype–phenotype correlations suggest that a wide spectrum of wall thickness can be found in patients with HCM-related gene mutations . LV mass< 0.001) . Thus, LIn addition to left atrial dimensions, which are already part of the current risk prediction algorithms, impaired left atrial strain, or components thereof , are considered emerging early markers of diastolic dysfunction, which have been associated with several clinical outcomes, but not with SCD so far ,60.Prediction and prevention of SCD in HCM is a major challenge for physicians in daily practice. Despite still being limited by issues in terms of costs and availability, CMR has emerged over the last two decades as a powerful tool uniquely suited for this purpose, given the high accuracy in measuring traditional imaging parameters beyond the unique capability of providing non-invasive tissue characterization. Recent international guidelines have upgraded the value of CMR in SCD risk stratification algorithms. An emblematic case report highlights the added role of CMR in SCD risk stratification in HCM patients, showing its crucial contribution in unmasking high-risk patients who would not be otherwise identified on traditional clinical and imaging assessment.