Hybrid FDG-PET/CT may also be used in the evaluation of extracardiac inflammation, permitting the identification of biopsy sites for diagnostic confirmation. Herein we examine the approach to diagnosis and management of CS using multimodality imaging via a case-based review.Cardiac sarcoidosis (CS) is an increasingly recognized cause of heart failure and arrhythmia. Historically challenging to identify, particularly in the absence of extracardiac sarcoidosis, diagnosis of CS has improved with advancements in cardiac imaging. Recognition as well as management may require interpretation of multiple imaging modalities. Echocardiography may serve as an initial screening study for cardiac involvement in patients with systemic sarcoidosis. Cardiac magnetic resonance imaging (CMR) provides information on diagnosis as well as risk stratification, particularly for ventricular arrhythmia in the setting of late gadolinium enhancement. More recently,  Sarcoidosis is a multiorgan system disease characterized by noncaseating granulomatous inflammation –3. Sarco18F-fluorodeoxyglucose position emission tomography (FDG-PET) scan, and/or late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR)  either in the heart or another organ in addition to characteristic clinical and imaging findings. Several diagnostic criteria for CS have been proposed, including the Japanese Ministry of Health and Welfare (JMHW) criteria  and the ng (CMR) . Howeverng (CMR) , 10, 11,ng (CMR) . More reng (CMR) . Notablyng (CMR) , ECG hasng (CMR) . HRS guing (CMR) .Here we provide a case-based review of multimodality cardiac imaging, specifically echocardiography, CMR, and FDG-PET, in CS, with an emphasis on diagnostic and management strategies . We alsoA 42-year-old male with a history of previously treated, well controlled pulmonary sarcoidosis presents with 3 months of progressive dyspnea on exertion, weight gain and fatigue. Physical exam is notable for elevated jugular venous pressure, bilateral inspiratory rales and pitting pretibial edema. He is referred for an echocardiogram, which demonstrates low normal left ventricular systolic function with an LVEF of 50–55%, moderate concentric left ventricular (LV) hypertrophy, restrictive diastolic filling pattern  and mild hypokinesis of the right ventricle. Global longitudinal strain (GLS) is reported at −6% . Given concern for restrictive cardiomyopathy, he is referred for endomyocardial biopsy, which demonstrates fibrosis without active granulomatous inflammation. Ongoing suspicion for cardiac involvement of sarcoidosis prompts advanced cardiac imaging, ultimately confirming a diagnosis of CS. He is initiated on corticosteroids and mycophenolate mofetil.E/A ratio ≥ 2 and findings consistent with increased left atrial pressure)  remains a cornerstone in the investigation of patients with suspected CS . TTE is ressure) . Severalressure) , 18. Howressure) , 19.More recently, advanced techniques such as speckle tracking echocardiography (STE) have shown promise in identifying subclinical myocardial dysfunction in CS. The tracking of grayscale speckles within the myocardium over the cardiac cycle allows for assessment of myocardial deformation using measurements such as strain, or change in length compared to baseline length , 21. STEP = 0.001) and right ventricular global longitudinal strain, RVGLS  among those with CS  for heart failure, while serial TTE may be used to monitor response to medications or potentially identify candidates for advanced heart failure therapies and devices , 10, 29.A 63-year-old African American female with a history of hypertension and dyslipidemia presents to the emergency department with 1 week of intermittent chest pressure and palpitations. ECG on arrival shows sinus rhythm with a nonspecific intraventricular conduction delay and occasional premature ventricular contractions. Serum troponin levels are undetectable. Chest x-ray is notable for an enlarged cardiac silhouette and hilar lymphadenopathy. Transthoracic echocardiogram reveals global LV systolic dysfunction with LVEF 40% and thinning of the basal septal wall. Coronary angiography shows non-obstructive coronary artery disease. She is referred for CMR, which shows midwall delayed gadolinium enhancement in the inferolateral basal septal LV, suspicious for CS. For further diagnostic evaluation, she undergoes bronchoscopy with endobronchial ultrasound-guided lymph node biopsy. Histopathology demonstrates macrophages and noncaseating granulomas. Given histologic confirmation of sarcoidosis, CMR findings and in context of borderline LV function, electrophysiology study is performed for further arrhythmic risk stratification and demonstrates inducible ventricular tachycardia. She undergoes implantable cardioverted-defibrillator (ICD) placement and initiation of immunosuppressive therapy for CS.CMR has established a role as a highly sensitive tool with both diagnostic and prognostic value in the management of CS. CMR has wide application in the evaluation of nonischemic cardiomyopathies, in part owing to the ability to identify myocardial fibrosis by LGE . MidwallP = 0.0014) on multivariate analysis (P = 0.03) and ventricular arrhythmia  in LGE-positive patients compared to LGE-negative patients  , sustained ventricular tachycardia, and aborted sudden cardiac arrest remain class I indications for an ICD by the most recent HRS guidelines , 54, whi= 0.024) . Thus, C= 0.024) .LGE-CMR is not without limitations. While sensitive to even small regions of fibrosis , 35, midA 49-year-old male with a history of biopsy-proven pulmonary sarcoidosis and recent complete heart block status post permanent pacemaker presents in clinic for further evaluation of possible cardiac involvement of sarcoidosis. ECG demonstrates sinus rhythm with right ventricular pacing. TTE shows normal biventricular size and function. CMR reveals LGE localized to the basal septum. He is referred for cardiac FDG-PET, which demonstrates patchy FDG uptake involving the basal septal and inferolateral LV wall with co-localized perfusion defects, concerning for active CS. A course of prednisone and methotrexate are initiated and 4 months later FDG-PET scan is repeated showing near resolution of cardiac FDG uptake. Pacemaker interrogation reveals recovery of AV node conduction.18F-FDG is a glucose analog that is readily utilized by activated macrophages  using rubidium-82 or N-13-ammonia   .18F-FDG in the setting of physiologic uptake by cardiac myocytes, alternative radiotracers have been explored to improve the specificity of PET imaging in CS , which targets the somatostatin receptor (SSTR) 2 subtype that is highly expressed in sarcoid granulomas but not in normal cardiac myocytes  compared to patients with normal imaging (P < 0.001). Similarly, among 67 patients with CS who were referred for FDG-PET, intensity of FDG uptake  was associated with increased incidence of cardiac events (For patients with CS, FDG-PET imaging also conveys important prognostic information. Blankstein et al. found that among 118 patients referred for FDG-PET for evaluation of possible CS, the presence of both perfusion defects and FDG uptake was associated with increased incidence of death or sustained ventricular tachycardia (HR 3.94, 95% CI 1.50–10.31,  imaging . Notablyc events . Other sc events , 90. The18F-FDG and CMR images, demonstrating the value of this modality for diagnosis, prognosis, and potentially cost-saving (The pathophysiology of CS lends itself to the complementary imaging modalities of echocardiography, CMR and FDG-PET for purposes of diagnosis, management, and prognostication. A proposed algorithm for imaging in CS is provided in t-saving . Notablyt-saving . Howevert-saving , 68. By t-saving . FDG-PETt-saving , 67. Impt-saving , reflectBeyond confirming a diagnosis, the management of CS also relies heavily on multimodality imaging. As previously detailed, FDG-PET has shown to be an effective tool for monitoring response to and tailoring immunosuppression. Serial echocardiographic evaluation is invaluable for longitudinal assessment of LV function to guide GDMT and, if needed, identify candidates for advanced therapies including left ventricular assist devices and orthotopic heart transplant , 5, 11. CS is a disease of complex pathophysiology that is well-suited to a multimodality imaging approach for purposes of diagnosis, treatment, and prognostication. Together, TTE, CMR and FDG-PET provide complementary clinical information that allows for a comprehensive understanding of the extent of cardiac involvement for each individual patient . OngoingNG and AW conceived the design of the paper. AW completed the initial manuscript draft for review. ES assisted with design of figures and made critical revisions to the paper. NG, JC, MM, and AH made critical revisions to the intellectual content of the paper. All authors approved the final manuscript for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Various adverse outcomes such as mortality and rehospitalization are associated with left ventricular non-compaction (LVNC). Due to data limitations, prospective risk assessment for LVNC remains challenging. This study aimed to investigate the influence of right ventricular (RV) dysfunction on the clinical outcomes of patients with LVNC through accurate and comprehensive measurements of RV function.p = 0.0155). After a follow-up period of 69.0  months, 18 (15.4%) patients reached the primary endpoint , with 14 (26.4%) and 4 (6.3%) from the RV dysfunction group and normal RV function group, respectively. The Kaplan–Meier method and log-rank test revealed that patients with RV dysfunction had a higher risk of all-cause mortality than those in the control group . Similar results were obtained for patients with left ventricular ejection fraction (LVEF) <50% . The relationship between RV dysfunction and heart failure rehospitalization and implantation of implantable cardioverter-defibrillator (ICD)/cardiac resynchronization therapy (CRT) was not statistically significant (both p > 0.05). The multivariable Cox proportional hazard modeling analysis showed that RV dysfunction  and impaired RV global longitudinal strain (RVGLS)  were independent predictors of mortality rather than increased RV end-diastolic area and decreased LVEF (both p > 0.05).Overall, 117 patients with LVNC  were enrolled, including 53 (45.3%) and 64 (54.7%) patients with and without RV dysfunction, respectively. RV dysfunction was defined as meeting any two of the following criteria: (i) tricuspid annular systolic excursions <17 mm, (ii) tricuspid S′ velocity <10 cm/s, and (iii) RV fractional area change (FAC) <35%. The proportion of biventricular involvement was significantly higher in patients with RV dysfunction than in controls (RV dysfunction is associated with the prognosis of patients with LVNC. Left ventricular non-compaction (LVNC) is a rare cardiomyopathy that is characterized by a thin and compacted epicardial layer, trabeculae, and deep intertrabecular recesses in the left ventricular myocardium . It is aRight ventricular (RV) dysfunction occurs in a substantial proportion of patients with LVNC –11. An aPatients diagnosed with LVNC at the Peking Union Medical College Hospital based on the criteria described by Jenni  a non-c 12, 18), 1812, 1The clinical and demographic characteristics of the patients were collected from chart reviews, laboratory data, and auxiliary examinations at the time of enrollment. Baseline data, including age, sex, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and the levels of N-terminal fragment of pro-hormone brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), albumin (Alb), hemoglobin (Hb), and creatinine (Cr) were collected. The estimated glomerular filtration rate (eGFR) was calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation . TransthThe patients were regularly followed up at the outpatient cardiomyopathy clinic. Data including current status, medication use, and re-examination (if necessary), were obtained from clinical visits made regularly or telephone calls to ascertain readmission for worsening. All-cause death was assigned as the primary endpoint and recorded by chart review, telephone contact, and inspection of electronic files for death certificates. For patients without events, the date of the last contact was used for survival analysis. The secondary endpoints were re-hospitalization for cardiac reasons and ICD/cardiac resynchronization therapy (CRT) implantation.t-test (homoscedasticity) or Welch's correction (non-homoscedasticity). Non-normally distributed variables were compared using the Mann–Whitney U test. Categorical data were expressed as percentages and compared using Pearson's χ2-test or Fisher's exact test, as appropriate. Survival analysis was performed using the Kaplan-Meier method by defining the time-to-event as the interval from the baseline to the primary endpoint. Kaplan-Meier survival curves were compared using the log-rank test. A univariable Cox proportional hazard model was used to analyze the relationship between the primary endpoint and baseline variables, such as echocardiographic parameters, blood pressure, and serum biochemical parameters. Results were reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Variables with p < 0.05, at the univariable analysis or with a prior given clinical relevance were further tested using multivariable Cox regression analysis. Statistical significance was defined as a two-tailed p-value of < 0.05. Statistical analysis was performed using GraphPad Prism  and SPSS .One-sample Kolmogorov–Smirnov tests and histograms were used to check the normality of the continuous data. Continuous variables were expressed as mean ± SD  or median [interquartile range (IQR)] . Levene's test was performed to test the homogeneity of the variances. Normally distributed variables were compared using an unpaired p = 0.0437). The RV dysfunction group had higher NT-proBNP  and Cr  than the control group, and no significant difference in the eGFR values was found between the two groups. The baseline echocardiographic parameters are presented in p = 0.0155). Patients with RV dysfunction had higher RVEDA than those in the control group  and significantly impaired RV global longitudinal strain (RVGLS) . Furthermore, the RV dysfunction group had relatively high LVEDV , low LVEF , and impaired LV global longitudinal strain (LVGLS) . Heart failure medications, including β-blockers, angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), spironolactone, diuretics, and digoxin, were more frequently used during the follow-up period in the RV dysfunction group than in the controls .A total of 117 patients with LVNC  were finally enrolled after excluding two patients with a single ventricle and six with unavailable data. The demographic and baseline characteristics of all subjects are summarized in p = 0.0013). The Kaplan–Meier curve is shown in p > 0.05).During a median follow-up time of 69.0 months , 18 patients (15.4%) reached the primary endpoint, including 14 (26.4%) and 4 patients (6.3%) from the RV dysfunction group and the control group, respectively. Patients with RV dysfunction had a higher risk of all-cause mortality than those in the control group , more biventricular involvement , and higher RVEDA  were also found in the RV dysfunction group than in the controls. Differences in LVEF also existed between the two groups . However, no significant difference was found in LVEDV . In the LV dysfunction population, 12 patients (16.7%) reached the primary endpoint, including 11 (24.4%) from the RV dysfunction group and one patient (3.7%) from the control group. The same results were observed for higher risk of all-cause mortality  in the RV dysfunction group, and no significant difference was observed for heart failure rehospitalization and implantation of ICD/CRT (both P > 0.05). Furthermore, p = 0.0039). However, the difference of LVEF  and LVGLS  between two groups were not statistically significant.To assess the interaction of RV dysfunction with LV systolic dysfunction on patient prognosis, baseline characteristics and outcomes were analyzed in 72 patients with LVEF < 50%, including 45 (62.5%) and 27 (37.5%) patients with and without RV dysfunction, respectively . Higher p <0.05). However, when variables were introduced into the multivariable Cox regression models, only RV dysfunction  and impaired RVGLS  were identified as independent predictors of mortality, whereas decreased LVEF and increased RVEDA were not (both p > 0.05).This study confirmed the prognostic value of RV parameters in a relatively large population of patients with LVNC (117 patients) over a median follow-up period of more than 5 years. RV dysfunction is independently associated with all-cause mortality in patients with LVNC, even after correction for LV function. The impaired RVGLS measured by 2D strain imaging indicates early RV systolic function abnormalities and can also predict outcomes in patients with LVNC.Impaired RV systolic function (defined as RVEF <35% on cardiac MRI) was identified in 50% and 16% of the population, respectively, in two previous researches , 11. In Regardless of LV failure, RV dysfunction was identified as an independent prognostic marker for LVNC, which might be due to the following reasons.First, a remarkable RV non-compaction manifestation may indicate serious pathological changes in the myocardium. A substantial relationship between the non-compacted/compacted ratio and changes in global ventricular function has been reported, which may be not just in the LV . In our Second, RV dysfunction alone could be an indicator of a poor prognosis in heart failure. Aside from pathological changes, RV dysfunction may be secondary to severe LV failure. In this study, low LVEF, large ventricular size, elevated NT-proBNP, and more frequently use of heart failure medications were observed in the RV dysfunction group. These LV alterations can lead to RV pressure overload , ventricular interdependence associated with septal dysfunction and limited pericardial flexibility , 26, neuThird, management strategies for right heart failure remain limited. In addition to the use of diuretics to relieve symptoms, effective ways to improve the histological changes of the right ventricle are lacking. Simultaneously, the influence of left heart failure on prognosis has not been observed in this study, mainly because of the good management of left heart failure. Patients in the present cohort were regularly followed up in our clinical center, and medications including β-blockers, ACE inhibitors/ARBs, spironolactone, diuretics, and digoxin were used following current international guidelines . This isIn this study, the evidence obtained for heart failure rehospitalization and implantation of ICD/CRT was weak. Readmissions were mainly due to worsening symptoms including dyspnea. It is common for left-sided heart failure to receive more clinical attention, whereas signs of systemic congestion (such as edema) are prone to be ignored unless the condition is severe. ICD implantation mainly targets malignant arrhythmia to prevent sudden death. Likewise, CRT mainly indicates non-synchronized ventricular contraction caused by the left bundle branch block, which may not be relevant to RV dysfunction. Additionally, few patients choose to accept device therapies for financial reasons.RV function is not easily obtained and is a time-consuming procedure because of the complex geometry of the RV and the lack of specific right-sided anatomic landmarks to be used as reference points . To dateThis study has some limitations. This was a single-center study with 117 patients with LVNC included and the right ventricle was not optimally visualized in all cases, resulting in missing data on RV function parameters, such as tricuspid S′. Speckle tracking requires user experience and high-quality images, which are not currently recommended for routine RV assessment. Therefore, large sample-sized studies with long-term follow-up are required to confirm this association in patients with LVNC.This study demonstrated that RV dysfunction is a strong independent and incremental risk factor for all-cause mortality in patients with LVNC. Two-dimensional strain imaging by STE seems to be a quantitative tool for early RV systolic function abnormalities and is associated with outcomes in patients with LVNC. This finding may have implications for the risk assessment of patients with LVNC, suggesting a regular and quantitative assessment of RV function in patients with LVNC.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethical Committee of Peking Union Medical College Hospital, Chinese Academy of Medical Science. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.WW was responsible for data screening, data extraction and analysis, and writing of the manuscript. WC, XL, and LF were responsible for the echocardiography data and checked and reviewed the final manuscript. All authors contributed to the article and approved the submitted version.This work was sponsored by the Chinese National Natural Science Foundation (Grant Number 81670349) and the Beijing Natural Science Foundation (Grant Number 7172166).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Left ventricular (LV) fibrofatty infiltration in arrhythmogenic right ventricular (RV) dysplasia/cardiomyopathy (ARVD/C) has been reported, however, detailed cardiovascular magnetic resonance (CMR) characteristics and association with outcomes are uncertain. We aim to describe LV findings on CMR in ARVD/C patients and their relationship with arrhythmic outcomes.CMR of 73 subjects with ARVD/C according to the 2010 Task Force Criteria (TFC) were analyzed for LV involvement, defined as ≥ 1 of the following features: LV wall motion abnormality, LV late gadolinium enhancement (LGE), LV fat infiltration, or LV ejection fraction (LVEF) < 50%. Ventricular volumes and function, regional wall motion abnormalities, and the presence of ventricular fat or fibrosis were recorded. Findings on CMR were correlated with arrhythmic outcomes.PKP2 genetic mutation variants, regardless of proband status. Only RV structural disease on CMR  and prior arrhythmia  were independently associated with arrhythmic events.Of the 73 subjects, 50.7% had CMR evidence for LV involvement. Proband status and advanced RV dysfunction were independently associated with LV abnormalities. The most common pattern of LV involvement was focal fatty infiltration in the sub-epicardium of the apicolateral LV with a “bite-like” pattern. LGE in the LV was found in the same distribution and most often had a linear appearance. LV involvement was more common with non-Among patients with 2010 TFC for ARVD/C, CMR evidence for LV abnormalities are seen in half of patients and typically manifest as fibrofatty infiltration in the subepicardium of the apicolateral wall and are not associated with arrhythmic outcomes.The online version contains supplementary material available at 10.1186/s12968-020-00702-3. PKP2) . Similarly, PLN, DSP, DSG2 and DSC2 carriers were found to have higher rates of LV dysfunction compared to PKP2 [PLN variants were more likely to have LV involvement compared with desmosomal mutation carriers [DSP variant was more common in patients with LV dysfunction [PKP2 variants in our cohort, our findings align with prior reports such that non-PKP2 variants carriers had a higher likelihood of exhibiting LV disease such as WMAs, low LVEF, LV-LGE and LV-fat  [PKP2 mutation carriers and diffuse LV fibrosis and dysfunction among DSP mutation carriers [Previous studies have shown that certain ARVD/C variants are strongly associated with LV fibrofatty changes, regardless of proband status –29. In mcarriers . Similar to PKP2 . Similarcarriers . In a stfunction . Despiteat Table . InteresP, DSG2) , 29, 32.carriers .DSP variants in European cohorts [LV abnormalities have been inconsistently associated with adverse outcomes in ARVD/C. Several European groups have shown a strong, independent association of LV dysfunction with cardiac death or life-threatening arrhythmias , 3, 7. H cohorts . These r cohorts . In anot cohorts .The significance of these regional abnormalities of the LV wall, independent of global LV dysfunction, has not been previously described in imaging studies. A prior study has also reported inducible LV-based VTs during electrophysiological studies performed in ARVD/C patients. The VTs localized to the LV posterolateral wall, corresponding to the most common location of involvement of LV fat and fibrosis on CMR . These fOur study has several limitations. First, this is a retrospective study of a cohort of ARVD/C patients from a tertiary care center, which may result in referral bias, however, this is unavoidable given the rarity of this disease. Second, given the known regional/ethnic variability in ARVD/C-associated pathogenic mutations leading to unbalanced predominance of PKP2-positive patients in our North-American cohort, we are limited in our ability to draw statistically significant conclusions with regards to any genetic association in terms of LV involvement. Third, we do not have pathologic proof the LGE identified at CMR represents myocardial fibrosis, although this concept has been supported by a large body of literature in ischemic and non-ischemic cardiomyopathies . Fourth,In a North American cohort of ARVD/C patients, LV involvement was found in half of the patients. LV disease is most often characterized by fibrofatty infiltration in the sub-epicardium of the apico-lateral wall. Fat infiltration was often seen in a bite-like pattern, which may be a unique marker of ARVD/C. Although LV abnormalities were more common in patients experiencing arrhythmic events, there was no significant independent association with outcomes on multivariable analysis. History of prior arrhythmic event and extent of RV disease are the only significant predictors of arrhythmic events after CMR.Additional file 1. Cardiac MRI protocol and supplemental tables and figures.


Cardiovascular magnetic resonance T1ρ mapping may detect myocardial injuries without exogenous contrast agent. However, multiple co-registered acquisitions are required, and the lack of robust motion correction limits its clinical translation. We introduce a single breath-hold myocardial T1ρ mapping method that includes model-based non-rigid motion correction.A single-shot electrocardiogram (ECG)-triggered balanced steady state free precession (bSSFP) 2D adiabatic T1ρ mapping sequence that collects five T1ρ-weighted (T1ρw) images with different spin lock times within a single breath-hold is proposed. To address the problem of residual respiratory motion, a unified optimization framework consisting of a joint T1ρ fitting and model-based non-rigid motion correction algorithm, insensitive to contrast change, was implemented inline for fast (~ 30 s) and direct visualization of T1ρ maps. The proposed reconstruction was optimized on an ex vivo human heart placed on a motion-controlled platform. The technique was then tested in 8 healthy subjects and validated in 30 patients with suspected myocardial injury on a 1.5T CMR scanner. The Dice similarity coefficient (DSC) and maximum perpendicular distance (MPD) were used to quantify motion and evaluate motion correction. The quality of T1ρ maps was scored. In patients, T1ρ mapping was compared to cine imaging, T2 mapping and conventional post-contrast 2D late gadolinium enhancement (LGE). T1ρ values were assessed in remote and injured areas, using LGE as reference.Despite breath holds, respiratory motion throughout T1ρw images was much larger in patients than in healthy subjects . In patients, the model-based non-rigid motion correction improved the alignment of T1ρw images, with higher DSC , and lower MPD . This resulted in significantly improved quality of the T1ρ maps . Using this approach, T1ρ mapping could be used to identify LGE in patients with 93% sensitivity and 89% specificity. T1ρ values in injured (LGE positive) areas were significantly higher than in the remote myocardium .The proposed motion-corrected T1ρ mapping framework enables a quantitative characterization of myocardial injuries with relatively low sensitivity to respiratory motion. This technique may be a robust and contrast-free adjunct to LGE for gaining new insight into myocardial structural disorders.The online version contains supplementary material available at 10.1186/s12968-021-00781-w. Research on quantitative magnetic resonance imaging has led to a greater understanding of the biochemical properties of human tissues. In particular, T1 rho (T1ρ) mapping has revealed new insights about the macromolecular content of biological tissues by showing substantial sensitivity to static processes and proton exchange and has added new information about compositional changes in human spinal disc degeneration, knee osteoarthritis, brain disease and liver fibrosis . The ideThe T1ρ relaxation describes the spin–lattice relaxation time in the rotating frame and was first introduced in vivo by Martino and Damadian in 1984  ms and FSL = 500 Hz. Imaging was performed at a simulated heart rate of 60 beats per minute.The ex vivo experiment is illustrated in Fig. To understand how the sequence performs in vivo and whether the motion correction impacts the T1ρ values, eight healthy subjects  without a history of cardiac disease were scanned with the proposed sequence. The same parameters as in the previous ex vivo study were used except that 3 short axis slices were acquired . The T1ρ mapping sequence was acquired during breath holds and timed such that the data acquisition occurred at mid-diastole.A patient study was performed to assess the performance of the sequence in a more challenging population and to validate its integration in a clinical workflow. From July 2020 to October 2020, 30 adult patients  referred for CMR at Haut-Lévêque Hospital in Bordeaux, France were prospectively included. Patients were not consecutive as the inclusion depended on the clinical workflow and was also impacted by competing research projects on similar patients. The inclusion criterion was an indication for CMR as part of standard care. Exclusion criteria were any contraindications to CMR. The CMR protocol consisted of cine bSSFP imaging , pre-contrast T1To quantify motion and assess the performance of motion correction in the ex vivo heart, healthy subjects and patients, epicardial and endocardial myocardial boundaries were drawn on each T1ρ-weighted image (non-corrected and motion-corrected), using a custom MATLAB software. The Dice similarity coefficient (DSC)  was calcIn the ex vivo heart, T1ρ values were extracted from 3 region of interests (ROIs) drawn on the septum and the remote LV free wall, as well as within the infarcted area exhibiting wall thinning. These were compared to ground truth values from the static acquisition. Signal intensity profiles along a transmural septal radius  to assess LV volume and ejection fraction (LVEF). Two experienced radiologists  qualitatively analysed cine, T1ρ maps, T2 maps and LGE images in consensus. Assessment of segmental wall motion abnormality was visually performed, and segments were graded as 0 for normal; 1 for mild or moderate hypokinesia; 2 for severe hypokinesia; 3 for akinesia; and 4 for dyskinesia  and 88.9% [95% confidence interval 68.2–98.9%], respectively. Examples illustrating excellent agreement between T1ρ value elevation and LGE are shown in Fig. although the residual motion during breath-held myocardial T1ρ mapping acquisitions can be considered negligible in healthy subjects, it is much larger in patients, and significantly impacts the quality of T1ρ maps,model-based non-rigid motion correction can be effectively applied to address this issue and improve the quality of myocardial T1ρ maps,motion-corrected T1ρ mapping may allow for the detection of acute and chronic myocardial injuries of various origins in patients, without the need for exogenous contrast agents.The main findings of this study are thatIn practice, robust non-rigid motion correction of pre-contrast myocardial T1ρ maps has been poorly addressed until now. The robustness is particularly needed when registering images with large contrast differences such as the first and last spin lock points  where conventional deformable registration algorithms could fail. Previous studies, also making use of breath-holding, made the assumption that residual motion artefacts caused by poor breath-holding are negligible for short breath-holds , 28. In In this pilot study, we demonstrate the feasibility of an inline non-rigid motion corrected myocardial T1ρ mapping framework to robustly quantify myocardial injury without the need for exogenous contrast agent. We highlight the importance of simultaneously performing joint non-rigid registration and T1ρ model fitting to deal with multi-contrast T1ρ-weighted images and to address the need of providing broader adoption of 2D myocardial T1ρ mapping in clinical practice.The performance of the proposed framework was first evaluated on an ex vivo human heart with a motion-controlled experimental setup and further assessed in vivo in eight healthy subjects and 30 patients with a broad spectrum of ischemic and non-ischemic injuries. An essential part of the technique is the complete automation of the reconstruction with fast inline reconstruction (~ 30 s). This is crucial for direct image analysis, clinical acceptance and future widespread clinical use.The proposed strategy pools the pair-wise non-rigid motion correction and T1ρ fitting in a unified optimization framework. As compared to non-corrected images, the non-rigid model-based motion correction significantly improves the T1ρ map quality. By exploiting the signal model, the method becomes robust to contrast change, as opposed to a standard intensity-based deformable registration , 10 and Other model-based registration approaches could also be employed for myocardial T1ρ mapping. For example, the technique proposed by Hue et al. , which cMoreover, while a simple mono-exponential signal model was considered in this pilot study, more advanced Bloch equation or extended phase graph simulations could be integrated into the reconstruction framework. By taking into consideration more information about the sequence, such as magnetization transfer, off-resonance, B1 inhomogeneities, slice profile and other complicating factors, dictionary-based simulations would provide more accurate and precise myocardial T1ρ maps.We have observed in patients that respiratory motion of the heart, when not corrected, can considerably deteriorate the quality of the reconstructed T1ρ maps, making LV segmental analysis highly unreliable. In patients, DSC scores were higher, MPD were lower, and image quality was improved after motion correction.Our patient study was not designed to assess the accuracy of myocardial T1ρ mapping in detecting myocardial injuries as compared to conventional LGE imaging. However, similar to previous studies , 11, 29,The study has several limitations. Firstly, for practical reasons, this study only included a limited number of patients and, in these, T1ρ mapping was only performed on 3 discrete slices, as opposed to a whole LV coverage on LGE imaging. Because T1ρ mapping was performed pre-contrast without any prior knowledge about presence, extent, and location of scar, T1ρ data was not available in a significant number of patients with LGE lesions. In addition, only a small number of acute injuries exhibiting high T2 values were available for comparison. Larger clinical studies are required to further validate the proposed motion-corrected T1ρ mapping technique and to assess its sensitivity, specificity and diagnostic value in patients with chronic and acute myocardial injuries. In particular, infarct location, size, extent, and transmurality are features that would ultimately need to be compared between T1ρ mapping and standard LGE imaging. Comparisons with conventional T1 and T2 mapping techniques will also have to be consistently performed to further elucidate the added value of T1ρ mapping and to better understand whether this may provide us with complementary quantitative information on myocardial tissue composition. Another limitation lies in the lack of a reference standard, such as histology. In the present study, an ex vivo human heart was used to optimize motion correction parameters, but the infarct present in this organ could not be considered as a reference for T1ρ in scar, due to changes induced by the fixation and preservation protocol. Thus, the performance of our technique in the assessment of myocardial injuries was limited to the comparison to conventional post-contrast LGE imaging in patients.A last set of limitations is related to the proposed model-based non-rigid motion correction framework, which cannot account and correct for through-plane motion but only residual in-plane respiratory motion. We acknowledge that residual through-plane motion may also affect the quality of the reconstructed T1ρ map. Solutions to this problem may include real-time slice tracking using diaphragmatic navigators. However, as the signal intensity at the lung-liver interface depends on the variable spin lock times, straightforward solutions may not easily be found. An alternative and most obvious solution includes 3D T1ρ mapping –32. The The proposed myocardial T1ρ mapping framework with model-based non-rigid motion correction enables a quantitative characterization of myocardial injuries with relatively low sensitivity to respiratory motion. This technique may be a robust and contrast-free adjunct to LGE for gaining new, additional, and quantitative insight into acute and chronic myocardial structural disorders.Additional file 1. Comparisons of non-adiabatic and adiabatic T1ρ-prepared single-shot images in a healthy subject.Additional file 2. Examples of T1ρ-weighted images and corresponding T1ρ maps before and after motion correction in two patients with high (top row) and low (bottom row) reduction of maximum perpendicular distance.Additional file 3. Dice scores (DSC) and maximum perpendicular distance (MPD) obtained in patients before and after model-based non-rigid motion correction on a T1ρ-weighted image level  and on a short-axis slice level .Additional file 4. Convergence of the proposed model-based non-rigid motion correction algorithm for myocardial T1ρ mapping.Additional file 5. Comparison of the proposed model-based non-rigid registration with standard deformable registration in a patient.Additional file 6. Visual comparisons of the proposed model-based non-rigid registration with a pair-wise registration using mutual information as similarity criterion for myocardial T1 rho mapping in two patients.


In Europe, liver cirrhosis represents the fourth-most common cause of death, being responsible for 170,000 deaths and 5500 liver transplantations per year. The main driver of its decompensation is portal hypertension, whose progression radically changes the prognosis of affected patients. Transjugular intrahepatic portosystemic shunt (TIPS) is one of the main therapeutic strategies for these patients as it reverts portal hypertension, thus improving survival. However, the coexistence of portal hypertension and pulmonary hypertension or heart failure is considered a contraindication to TIPS. Nevertheless, in the latest guidelines, the definition of heart failure has not been specified. It is unclear whether the contraindication concerns the presence of clinical signs and symptoms of heart failure or hemodynamic changes in the right heart-pulmonary circulation. Moreover, data about induced right heart volume overload after TIPS and the potential development of heart failure and pulmonary hypertension is currently scanty and controversial. In this article we revise this issue in finding predictors of cardiac performance after TIPS procedure. Performing a fluid challenge during right heart catheterization might be a promising expedient to test the adaptation of the right ventricle to a sudden increase in preload in the first few months after TIPS. This test may unmask a potential cardiac inability to sustain the hemodynamic load after TIPS, allowing for a clearer definition of heart failure and, consequently, a more robust indication to TIPS. In Europe, liver cirrhosis is the cause of 5500 liver transplantations per year and it constitutes the fourth most-common cause of death, resulting in 170,000 deaths per year , which ePortal hypertension is a syndrome caused both by an increased resistance in the portal intrahepatic circulation and by increased splanchnic blood flow. In healthy liver, the pressure difference between the portal and the hepatic veins does not usually exceed 5 mmHg. Portal hypertension is defined by a gradient greater than 6 mm Hg, even if clinical complications do not seem to occur until the gradient exceeds 10–12 mmHg . The preThe introduction of transjugular intrahepatic portosystemic shunt (TIPS) in clinical practice represented, in the last 20 years, a step forward for treatment improvement for patients with untreatable complications of portal hypertension.TIPS works as a shunt between the systemic and the portal circulation. It is obtained by percutaneously connecting an intra-parenchymal branch of the portal vein with a hepatic vein through a low-resistance conduit, embraced by a self-expandable metal stent. Thus, TIPS reduces the portal–caval pressure gradient. The current criteria for TIPS placement have been enlarged . ClinicaThe impact of TIPS on pulmonary hemodynamics is still poorly discussed in the scientific literature. Creation of a TIPS may critically influence the pulmonary circulation. Blood shifts from the splanchnic circulation to the systemic circulation, thus increasing cardiac preload. Such changes can be clearly evidenced utilizing invasive hemodynamic techniques through right heart catheterization. Indeed, blood shunting results in an increase in cardiac output (CO) and pulmonary artery pressure and a decrease in systemic vascular resistances . A recenFinally, it was shown that volume overload induced by TIPS placement may be associated with increased PAWP and, consequently, postcapillary pulmonary hypertension (group II WHO classification) ,22,23,24Cardiac assessment for elective TIPS insertion, according to guidelines , includeTIPS is contraindicated in patients with severe left ventricular dysfunction or severe pulmonary hypertension  . HoweverOn the other hand, a Consensus Conference on TIPS management published in 2017 proposed hemodynamic and echocardiographic thresholds contraindicating TIPS positioning in case of pulmonary hypertension . These thresholds, indicative of severe pulmonary hypertension (PH), would be predictive of cardiac dysfunction after TIPS. However, TIPS can be performed in mild PH (mPAP at RHC between 25 and 35 mmHg) . These dEven if there is a growing awareness of the importance of a correct cardiac evaluation, since blood shunting after TIPS is responsible for a consistent increase in right atrial pressure (RAP) and cardiac output (CO), predictive studies of adverse cardiac outcomes after TIPS are currently scarce and controversial . A studyThe proportion of patients with possible cardiac complications may further increase in the near future as patients with cirrhosis of metabolic origin are increasing in prevalence. These patients show concomitant diabetes, arterial hypertension, and/or high HDL cholesterol or triglycerides concentration in blood, and increased cardiovascular risk. For this reason, an accurate cardiac assessment becomes crucial in their evaluation before TIPS placement . The corUnfortunately, long-term changes in the pulmonary circulation-heart unit induced by volume overload after TIPS placement are currently overlooked in clinical practice ,30,31,36The potential impact of TIPS placement on the pulmonary circulation offers the opportunity to better clarify the correct balance of its clinical indication.According to current guidelines/consensus, increased right and/or left ventricular diastolic pressure would allow for TIPS contraindication even in the absence of structural heart diseases ,14. IndeInvasive hemodynamic assessment would also allow us to clearly identify increased pulmonary pressure, which represents a second important contraindication for TIPS placement. The correct measurement of PAWP allows definitively to identify precapillary pulmonary hypertension  from postcapillary pulmonary pressure  ,39.Additionally, RHC assessment gives us the unique opportunity to test the potential consequences of TIPS-derived volume overload on the pulmonary circulation-heart unit.Considering such important clinical consequences of TIPS placement, a fluid challenge during initial RHC could be a promising tool to correctly evaluate the potential hemodynamic changes induced in the pulmonary circulation-heart unit in patient candidates for TIPS.In recent years, indeed, many studies have shown that a fluid challenge with rapid saline infusion during RHC was useful to correctly identify hidden left heart failure related to left ventricular diastolic dysfunction in the absence of structural heart diseases . Fluid cThe fluid challenge test during initial RHC could help clinicians in the difficult task of deciding on TIPS indication in a different clinical setting. A relevant cut-off value of RAP increase during rapid saline infusion would probably improve our understanding for the correct balance between indication and contraindications to TIPS placement and provide essential information on outcomes for future decision-making processes.Further investigations on pulmonary circulation-heart unit behaviors and their influence on the outcome of TIPS are still required.


Background: The occurrence of atrial fibrillation is often accompanied by myocardial fibrosis. An increasing number of studies have shown that intestinal flora is involved in the occurrence and development of a variety of cardiovascular diseases. This study explores the relationship between changes in the structure and function of intestinal flora and the progression of myocardial fibrosis in patients with persistent atrial fibrillation.Methods: Serum and stool samples were collected from 10 healthy people and 10 patients with persistent atrial fibrillation (PeAF), and statistical analyses were performed on the subjects' clinical baseline conditions. ELISA was used to measure the levels of carboxy-terminal telopeptide of type I collagen (CTX-I), propeptide of type I procollagen (PICP), procollagen III N-terminal propeptide (PIIINP), fibroblast growth factor-23 (FGF-23), and transforming growth factor-beta 1 (TGF-β1) in serum. Through 16S rRNA sequencing technology, the structural composition of the intestinal flora was detected and analyzed. In addition, metabolomics data were analyzed to determine the differences in the metabolites produced by the intestinal flora of the subjects.Results: By comparing the baseline data of the subjects, it was found that compared with those of the control group, the levels of creatinine (CRE) and serum uric acid (SUA) in the serum of PeAF patients were significantly increased. In addition, we found that the levels of CTX-I, PICP, PIIINP, and TGF-β1 in the serum of PeAF patients were significantly higher than those of the control group subjects. Although the control and PeAF groups exhibited no significant differences in the α diversity index, there were significant differences in the β diversity indexes . At the phylum, family and species levels, the community structure and composition of the intestinal flora of the control group and those of the PeAF group showed significant differences. In addition, the compositions of the intestinal metabolites in the two different groups of people were significantly different. They were correlated considerably with PIIINP and specific communities in the intestinal flora.Conclusion: Pathologically, PeAF patients may have a higher risk of myocardial fibrosis. Systematically, abnormal changes in the structure and composition of the intestinal flora in PeAF patients may lead to differences in intestinal metabolites, which are involved in the process of myocardial fibrosis through metabolite pathways. Atrial fibrillation (AF) is one of the most common arrhythmias, and persistent atrial fibrillation (PeAF) is often associated with a higher risk of stroke . Atrial Imbalance in collagen synthesis and its decomposition and metabolism are the causes of the occurrence and development of myocardial fibrosis . It is wAs the concept of the “gut-heart” axis has gradually attracted attention, increasing evidence has confirmed the connection between the gut microbiota and cardiovascular diseases (CVDs), such as hypertension, atherosclerosis, myocardial infarction, heart failure, and arrhythmia , 12. AtrIn this study, based on 16S rRNA sequencing and metabonomic techniques, we investigated the correlation between atrial fibrosis and gut microbiota and their derived metabolites in PeAF patients. The mechanism of atrial fibrosis in PeAF patients was preliminarily explored from the perspective of “gut-heart.” This study may provide new ideas for the prevention and treatment of persistent atrial fibrillation.P > 0.05). The selection criteria for PeAF patients were based on the guidelines for atrial fibrillation recommended by the European Society of Cardiology (ESC)  . The excgy (ESC) . This stAll participants used a sterile stool collection kit to collect stool samples. After the sample was collected, it was quickly placed in a freezing tube, placed in liquid nitrogen for quick freezing, and then transferred to a −20°C refrigerator for storage. Five ml of fasting venous blood was collected from each subject, maintained at room temperature for 2 h, and then centrifuged at 2–8°C at 1,000 g for 15 min. The supernatant was then collected for subsequent experiments.According to the manufacturer's instructions, ELISA was performed using the following kits: CTX-I , PICP , PIIINP , FGF-23 , and TGF-β1 . After the reactions were terminated, the optical density  of each sample was sequentially measured at 450 nm wavelength with a microplate reader.Illumina NovaSeq PE250 was used for 16S amplicon sequencing to obtain raw data. The raw data were subjected to joint removal, filtering, deduplication, base correction, and removal of chimera sequences to obtain clean data for subsequent analyses. The QIIME 2 analysis process was adopted, and DADA2 was used to denoise the raw data, equivalent to clustering with 100% similarity. Only low-quality sequences were removed and corrected, and algorithms were identified and de-embedded. The denoised sequences were de-redundant. Additionally, feature [including Amplifier sequencing variation (ASV)] information was obtained. Each ASV sequence was annotated to obtain corresponding species information, including abundance distribution. QIIME 2 software was used to calculate the alpha diversity index  of each sample. The ANOSIM analysis method was used to test the significance of differences in the community structures of the grouped samples. R software was used to draw a PCoA dimensionality reduction analysis diagram based on Bray-Curtis, unweighted UniFrac, and weighted UniFrac distances (phyloseq/vegan package).2O (0.1% formic acid) and (B) acetonitrile, with an injection volume of 3 μl. Mass conditions were as follow: Time of Flight is 60–100 dm/z, Ion source Gas1is 55psi, Ion source Gas2 is 55psi, Curtain Gas is 35psi, Temperature is set to 550°C, Declustering potential is 80 V, Collision Energy is 10 V, IonSpray Voltage is 5500 V (POS) or −4500 V (NEG). According to the plain peak area obtained by detection from the detection and AB SCIEX (AB Sciex Pte Ltd.) commercial and self-built databases, relative quantification of metabolites was carried out. The signal correction of the LC-MS metabolomics raw data was performed by using the R language package Stattarget. Then, we use MetaboAnalyst 5.0  website online analysis for a series of subsequent analyses, including Principal Component Analysis (PCA), partial least-squares discrimination analysis (PLS-DA), orthogonal partial least-squares discrimination analysis (OPLS-DA), and Sparse PLS discriminant analysis (sPLS-DA). Kyoto Encyclopedia of Genes and Genomes  database was used for metabolic pathway analysis.After freezing and grinding each stool sample, ~50 mg was weighed and placed in a centrifuge tube. Four hundred microliter precooled (4°C) extraction solution (Methanol: Acetonitrile (v/v) = 1:1) was added to the sample tube, followed by vortexing and mixing, and then the mixed solution was incubated on ice for 10–15 min. Subsequently, the mixture was centrifuged at 16,000 g at 4°C for 10 min, and the supernatant was collected, transferred to a new centrifuge tube, and dried with nitrogen. The LC-MS analysis system consisted of an ultrahigh-performance liquid chromatograph (Agilent 7890B-5977B) paired with a Q Exactive Orbitrap high-resolution mass spectrometer (Thermo Fisher Scientific). The flow rate was set at 0.3 ml/min; the temperature of the sample tray was 4°C, and the column temperature was 40°C. A Waters HSS T3 column  was used with (A) Ht-tests or one-way analysis of variance (ANOVA). The measurement data that did not conform to a normal distribution were analyzed using the Wilcoxon rank-sum test. The Spearman correlation analysis method was used for correlation analysis. A p < 0.05 was considered significantly different.GraphPad  statistical software was used for the analyses. Variables conforming to a normal distribution are expressed as the mean ± standard deviation (SD). Comparisons between two groups were performed using First, we analyzed and compared the baseline characteristics of the 10 healthy people and the 10 PeAF patients included in this study. As shown in We first detected the expression of cardiac fibrosis markers in the serum of all the subjects. As shown in p > 0.05) (p < 0.1)  . Therefo > 0.05) . The unwp < 0.1) . These rP = 0.001) (As shown in = 0.001) . Further= 0.001) . At the = 0.001) . TherefoDorea  and g_Blautia_ASV_5 (Blautia genus) were significantly reduced in the PeAF group , g__Blautia_ASV_21 (Blautia genus), and Bacteroides_uniformis (Bacteroides) in the PeAF group were significantly increased  had a significant positive correlation with the CTX-I, PICP, PIIINP and FGF-23 level (p < 0.05). g__Blautia_ASV_21 (Blautia genus) was also significantly positively correlated with PICP, PIIINP and FGF-23 levels (p < 0.05). Bacteroides uniformis (Bacteroides genus) was positively correlated with the level of the myocardial fibrosis marker FGF-23 (p < 0.05), while g__Blautia_ASV_5 (Blautia genus) was significantly negatively correlated with FGF-23 and PIIINP level (p < 0.05) (As shown in AF group . The abuncreased . In addi < 0.05) .It is known that an essential way for the intestinal flora to exert positive and/or negative effects on the host is achieved through the metabolites produced by the flora. Therefore, we detected and analyzed the intestinal metabolites in the subjects in this study. As shown in t-tests to analyze the changes in metabolites in the control group and the PeAF group. The top 5 differential metabolites that decreased and increased the most in the two groups were shown in https://www.genome.jp/kegg/pathway.html), the functional metabolic pathways at the L1 level intestines PeAF patients changed significantly. In addition, 8 intestinal metabolites in the “valine, leucine, and isoleucine biosynthesis” pathway (L3 level) belonging to “amino acid metabolism” category (L2 level) were enriched in the PeAF patients (p = 1.07E-02); of these metabolites, C00671 [(S)-3-Methyl−2-oxopentanoic acid] and C00233 (4-Methyl-2-oxopentanoate) were significantly enriched in the intestines of the PeAF patients . Meanwhile, a total of 42 plasma metabolites in the “tyrosine metabolism” pathway (L3 level) belonging to the “amino acid metabolism” category (L2 level) were enriched in the PeAF patients (P = 5.32E-02), of which metabolites C00628 , C00642 (4-hydroxyphenylacetate), and C05582 (homovanillate) were significantly enriched in the intestines of patients in the PeAF group . In addition, 46 intestinal metabolites in the “Primary bile acid biosynthesis” pathway (L3 level) belonging to the “Lipid metabolism” category (L2 level) were enriched (P = 6.66E-02), including C01921 (Glycocholate), C05466 (glycochenodeoxycholate), and C05122 , which were significantly enriched in the intestines of the PeAF patients . These results indicate that the significantly enriched metabolites in the intestines of PeAF patients are related to the functional metabolic trends in amino acid metabolism and lipid metabolism pathways. Spearman's correlation analysis indicated that PIIINP significantly correlates with Urate, Erucate, Canrenone, and Furosemide (p < 0.05). In contrast, PIIINP has a significant negative correlation with 1,3-dimethyluric acid, 1,9-dimethyluric acid, Glycocholate, and glycochenodeoxycholate. FGF-23 is also significantly and negatively correlated with 1,3-dimethyluric acid and 1,9-dimethyluric acid. TGF-β1 was positively correlated with Urate and Erucate and negatively correlated with 2-hydroxy−2-methylbutyric acid. In addition, CTX-I, and PICP were positively correlated with Furosemide and Urate, respectively  is mediated by oxidative stress, neurohormonal activation, and inflammatory activation. Serum uric acid (SUA) is a surrogate indicator of oxidative stress . The redBlautia (Firmicutes phylum) has also been previously found to be significantly reduced in patients with chronic heart failure (Rothia (Actinobacteria phylum) has been found that was over-enriched in patients with certain diseases, such as pancreatic cancer and primary sclerosing cholangitis  in the PeAF patients, which may be related to differences in the pathological development of different diseases. Kaburova et al. found that both PICP and PIIINP were significantly and negatively correlated with beneficial intestinal bacteria and significantly positively correlated with several potentially harmful bacteria in the intestine  and g__Blautia_ASV_21 (Blautia genus) were significantly and positively correlated with PICP, PIIINP, and FGF-23 level, while g__Blautia_ASV_5 (Blautia genus) was significantly and negatively correlated with PIIINP and FGF-23 level. This finding suggests that the specific intestinal flora of PeAF patients may be involved in the process of myocardial fibrosis.In recent years, the role of intestinal flora in cardiovascular disease has gradually attracted attention. Researchers have found that in many diseases, including atrial fibrillation, the structure and composition of the intestinal flora change to a certain extent. In this study, although the alpha diversity of the intestinal flora between healthy people and PeAF patients was no apparent difference, we observed significant differences in the relative indexes in terms of beta diversity, such as Bray-Curtis, weighted UniFrac and Anosim. It implies that the steady state of the intestinal microbial community structure of the PeAF population had been altered. Similarly, in a previous investigation, researchers found that the abundance of gut microbes in AF patients was lower than that of people without atrial fibrillation. However, they found no differences in gut microbial diversity between the two groups . This re failure . Rothia langitis , 28. Pre failure . Howeverntestine . We founThe evidence obtained to date suggests that one of the potential mechanisms by which the intestinal flora has an impact on the host is by directly affecting the host through host-derived metabolites. For example, SCFAs produced through the metabolism of the intestinal flora can maintain the host's sugar, lipid and protein metabolism balance and reduce the occurrence and development of cardiovascular diseases . The metThere is evidence that excessive lipid accumulation can lead to apoptosis and mitochondrial dysfunction and increase cardiac fibrosis , 35. In We must admit that our study also has some limitations. On the one hand, the sample size included in this study was limited. It resulted in some changes that were not significantly different between the two groups . On the other hand, there was age bias between the two groups. Some of the differences in gut microbiota between individuals may be caused by age . AlthougIn summary, our research shows that the occurrence of atrial fibrillation is accompanied by a certain degree of intestinal flora disorder. In addition, the degree of cardiac fibrosis in patients with atrial fibrillation is closely related to the abundance and metabolic function of particular intestinal flora. These microbes may directly or indirectly participate in cardiac fibrosis through metabolic pathways in patients with atrial fibrillation. The results provide new insights into the relationship between atrial fibrillation-myocardial fibrosis and intestinal flora.https://www.ncbi.nlm.nih.gov/sra/PRJNA728204.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: The studies involving human participants were reviewed and approved by the Ethic Committee of Xiangya Hospital Central South University (202004176). The patients/participants provided their written informed consent to participate in this study.FL and LL designed the research and performed the research. JS and RL analyzed the data. All authors contributed to the writing and revisions and reviewed the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Similarly, TTE‐derived LVEDV and RVEDV were greater in EA versus HC . Both LVEF and RVEF were lower in EA versus HC, with the most pronounced difference observed in RVEF via TTE (9%) (p < 0.001). LV stroke volume was greater in EA versus HC via both CMR (18.5%) and TTE (13.2%) (both p < 0.05). Few studies reported data for the mixed athlete (MA) population and even fewer studies reported data for strength athletes (SA), therefore a limited analysis was performed on MA and no analysis was performed on SA. This evidence‐synthesis review demonstrates the RV may be more susceptible to ventricular enlargement. General changes in LV and RV structure and function in female EA mirrored changes observed in male counterparts. Further studies are needed to determine if potential adverse outcomes occur secondary to these changes.We conducted a meta‐analysis to synthesize the best available evidence comparing cardiac biventricular structure and function using cardiac magnetic resonance imaging (CMR) and transthoracic echocardiography (TTE) in elite female athletes and healthy controls (HC). Chronic exposure to exercise may induce cardiac chamber enlargement as a means to augment stroke volume, a condition known as the “athlete's heart.” These changes have not been clearly characterized in female athletes. Multiple databases were searched from inception to June 18, 2019. Outcomes of interest included left ventricular (LV) and right ventricular (RV) dimensional, volumetric, mass, and functional assessments in female athletes. Most values were indexed to body surface area. The final search yielded 22 studies, including 1000 female athletes from endurance, strength, and mixed athletic disciplines. CMR‐derived LV end‐diastolic volume (LVEDV) and RV end‐diastolic volume (RVEDV) were greater in endurance athletes (EA) versus HC (17.0% and 18.5%, respectively; both  This article focuses on the morphological and physiological effects of endurance‐based exercise on the female heart. Much literature has been described in males, but this data features data that mirrors that of men and particularly focuses on left and right ventricular function using established and advanced imaging modalities. Athletes were assigned to specific sport categories based on the static and dynamic components of the activities they participated in according to the Mitchell classification of sports . Data included LV end‐diastolic volume (LVEDV ml/m2), LV end‐systolic volume , LV end‐diastolic diameter , LV end‐systolic diameter , LV mass , LV wall thickness (mm/m2), RV end‐diastolic area , RV end‐systolic area , RV end‐diastolic volume , RV end‐systolic volume , and RV mass . Volumetric assessment of the RV by TTE was obtained with three‐dimensional (3D) technology in selected studies. Secondary outcomes included assessment of ejection fraction , stroke volume , tricuspid annular plane systolic excursion , and fractional area change .We extracted primary outcomes data pertinent to left ventricle (LV) and RV structural and functional measurements ascertained by using functional parameters through CMR and TTE. Values other than those expressed by a percentage were indexed to body surface area  or senior investigators . When a study was deemed eligible, the reviewers moved it to data extraction, determined its methodological quality, and collected descriptive and outcome data. Reviewers extracted data on patient demographics and relevant baseline characteristics , study design and variable, and outcomes of interest. All steps of data screening and abstraction were conducted blindly, independently, and in duplicate (by two reviewers).2.5We used the Newcastle‐Ottawa Scale (NOS) for cohort and case‐control studies. Due to the non‐comparative nature of the available studies, we used a modified NOS in which we discounted the comparability criteria, thus assessment of risk of bias  focused on outcome ascertainment, cohort selection, and attrition , <0.0029 (comparisons between MA and controls), and <0.0063 (comparisons between EA and MA) were considered statistically significant. All statistical tests were two‐sided. Statistical analyses were performed using R Statistical Software .Comparisons of outcomes between EA and healthy controls (HC), between mixed athletes (MA) and HC, and between EA and MA were made using a random effects meta‐analysis for continuous outcome variables , LVSV , and LVM  were greater in EA versus HC. LVEF tended to be ~2% lower in EA versus HC .When assessed using CMR, LVEDV , an 18.5% greater RVSV , and a 22% greater RVM  in EA versus HC. RVEF . A graphical representation of differences in LVEDV and RVEDV is shown in Figure Assessment of RV function via CMR revealed an 18.5% greater RVEDV  and a 27% greater LVESV . LVEF . Assessment of RV function revealed a 28% greater RVEDV  and a 37% greater RVESV . RVEF .Transthoracic echocardiography assessment of LV size revealed a 17% greater LVEDV  in EA compared to HC. Although not statistically significant, there was a trend toward a lower LVEF in EA compared to HC when assessed with both CMR and TTE. The same was true when assessing the RV with CMR with a lower RVEF in EA versus HC (p = 0.015). However, TTE‐ derived RVEF was lower in EA compared to HC (p < 0.001). Figure This evidence‐synthesis review summarized the evidence of biventricular size and function in female athletes. Findings demonstrated marked changes in ventricular size and modest changes to function in a manner similar to that of male athletes .6This work will advance providers medical knowledge with regards to normative structural and functional values when assessing female athlete's hearts with TTE or CMR.7The primary impediment with performing this study was the limited data available on TTE and CMR analysis of the female athlete's heart. Therefore, further investigations are necessary in order to develop standard reverence values with TTE and CMR imaging in this population. Additionally, advanced imaging techniques such as exercise CMR may define adaptations in the RV and LV undergo when stressed to potentially identify potential pathological adaptations.There was no funding for this paper.None declared.The authors confirm contribution to the paper as follows: study conception and design: Robyn Bryde, Andres Applewhite, Brian Shapiro, and M. Abu Dabrh; data collection: Robyn Bryde, Andres Applewhite, Larry Prokop, Tara Brigham, Michael Heckman, and Carlos Rojas; analysis and interpretation of results: M. Abu Dabrh, Robyn Bryde, Andres Applewhite, and Brian Shapiro; draft manuscript preparation: Bryan Taylor, Sara Filmalter, George Pujalte, Alexander Heckman, Brian Shapiro, and Robyn Bryde. All authors have reviewed the results and approved the final manuscript.Appendix S1Click here for additional data file.Appendix S2Click here for additional data file.Appendix S3Click here for additional data file.Appendix S4aClick here for additional data file.Appendix S4bClick here for additional data file.


We evaluated if impaired coronary vascular function, assessed by rubidium-82  and had a higher prevalence of left ventricular hypertrophy (p < 0.001), a lower hyperemic myocardial blood flow (MBF), and myocardial perfusion reserve (MPR) (both p < 0.001) compared to those without. Conversely, coronary artery calcium content and baseline MBF were not different between patients with and without RH. At univariable Cox regression analysis, age, RH, left ventricular ejection fraction, coronary artery calcium score, and reduced MPR were significant predictors of events. At multivariable analysis, age, RH, and reduced MPR  were independent predictors of events. Patients with RH and reduced MPR had the highest risk of events and the major risk acceleration over time.Over a median of 38 months (interquartile range 26 to 50), 21 cardiac events (4.1% cumulative event rate) occurred. Patients with RH were older (The findings suggest that the assessment of coronary vascular function may enhance risk stratification in patients with hypertension. Patientve (MPR) , 4. By ive (MPR)  and in tve (MPR) –8. Previve (MPR)  and loweb PET/CT . However82Rb PET/CT as part of their diagnostic workup. For the purpose of the present investigation, 1237 hypertensive patients with known CAD, 166 with abnormal myocardial perfusion imaging, and 120 with heart failure were excluded. Follow-up data were not available in 35 (6%) of the remaining 552 patients, leaving 517 subjects for the analysis. For each patient, the presence of coronary risk factors was noted. Arterial hypertension was defined as repeated blood pressure (BP) measurements of ≥ 140 mmHg systolic and/or ≥ 90 mmHg diastolic and/or intake of antihypertensive medications [From March 2012 and March 2014, 2075 hypertensive patients underwent stress-rest 82Rb cardiac PET/CT, patients were asked to discontinue taking methylxanthine containing foods or beverages for 24 hours. In all patients, anti-hypertensive medications were not discontinued before imaging studies. Scans were acquired using Biograph mCT 64-slice scanners . Rest and stress cardiac PET/CT images were acquired as follows: scout CT was performed to check patient position and low-dose CT  was performed for attenuation correction, during normal breathing before and after PET acquisitions. For both rest and stress imaging, 1110 MBq of 82Rb was injected intravenously with a 7-min list-mode PET acquisition. Dynamic PET acquisition was started at rest followed by an adenosine pharmacologic stress test . Both rest and stress dynamic images were reconstructed into 26-time frames  using the vendor standard ordered-subsets expectation maximization 3D reconstruction  with 6.5-mm Gaussian post-processing filter. In addition, the images were corrected for attenuation using the low-dose CT. The heart rate, systemic BP, and 12-lead ECG were recorded at baseline and throughout the infusion of adenosine. External cardiac work was estimated as a rate-pressure product and was calculated as heart rate × systolic arterial BP. Myocardial perfusion, LV volumes, and EF were calculated using an automated software . LVEF reserve was computed as stress EF-rest EF [As a routine preparation for −1×g−1) was computed from the dynamic rest and stress imaging series with commercially available software (Siemens Syngo Dynamic PET) [Absolute MBF (in mL × minmic PET) . MPR wasmic PET) . The MPR2 and a density ≥ 130 HU. Coronary artery calcium (CAC) score was calculated according to the method described by Agatston et al. [Coronary calcification was defined as a plaque with an area of 1.03 mmn et al. . ExperieThe follow-up was obtained by the use of a questionnaire that was assessed by a phone call to all patients and by the review of hospital or physicians’ records by individuals blinded to the patient’s test results. The outcome was a composite endpoint of cardiac death, nonfatal myocardial infarction, coronary revascularization, or admission for heart failure whichever occurred first. The cause of death was confirmed by a review of the death certificate, hospital chart, or physician’s records. Death was considered to be of cardiac origin if the primary cause was defined as acute myocardial infarction, congestive heart failure, valvular heart disease, sudden cardiac death, and cardiac interventional/surgical procedure related. Myocardial infarction was defined when > 2 of the following 3 criteria were met: chest pain or equivalent symptom complex, positive cardiac biomarkers, or typical electrocardiographic changes . All host test and χ2 test were used to compare the differences in continuous and categorical variables, respectively. A p value < 0.05 (two-sided) was considered statistically significant. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated by univariable and multivariable Cox regression analysis. Variables showing a p value < 0.05 at univariable analysis were considered for multivariable analysis. Event-free survival curves were obtained by the Kaplan-Meier method and compared using the log-rank test. Annualized event rates (AER) were calculated as the cumulative number of events divided by person-time and expressed as events per 100 person-years. A parametric survival model was used to identify which variables influenced time to event and to estimate risk-adjusted event rates during follow-up [Continuous data are expressed as mean ± standard deviation and categorical data as a percentage. A student two-sample ollow-up , 18. BasOf the 517 patients enrolled, 136 (26%) had RH and 381 (74%) CH. Baseline patient characteristics and imaging findings according to hypertensive status are shown in Table Over a median follow-up of 38 months (interquartile range 26 to 50 months), 21 cardiac events (4.1% cumulative event rate) occurred: 3 cardiac deaths (14%), 4 myocardial infarctions (19%), 4 revascularization procedures (19%), and 10 admissions for heart failure (48%). Patients’ characteristics and imaging findings according to the occurrence of events are reported in Table p < 0.05). Interestingly, the event-free survival was similar in patients with RH and normal MPR and those with CH and reduced MPR (p = 0.47). The best outcome was observed in patients with CH and MPR ≥ 2. CH patients with reduced MPR showed no difference in AER as compared to those with normal MPR. Differently, RH patients with reduced MPR showed an AER significantly higher compared to those with normal MPR and compared to CH patients with reduced MPR (both p < 0.05).Univariable and multivariable Cox regression analyses are reported in Table The cumulative hazard and the median survival time predicted by Weibull analysis are illustrated in Fig. 82Rb PET/CT imaging, is associated with an increased risk of an adverse cardiac event in patients with RH [This study first demonstrates that the presence of coronary vascular dysfunction, assessed by  with RH . Among c with RH . Regardl with RH . Elevate with RH , 22.The duration and the grade of hypertension may influence the BP burden accumulated over time and this could explain the different incidence of complications in patients with and without RH . However82Rb PET/CT, in patients with RH. Our results indicated that, despite a normal myocardial perfusion, patients with RH have a high risk of cardiovascular events. In particular, it also emerged that the inability to adequately increase MBF in response to stress identify RH patients with a substantially higher rate of events compared to those with normal coronary vasodilator reserve and remaining at higher risk also compared with CH patients with reduced MPR.It has been clearly reported that in absence of known CAD, patients with normal perfusion and RH have an evidently impaired microvascular function compared with controlled hypertension , 10 probPrevious studies demonstrated that the evaluation of coronary vasodilator function improves the prognostic assessment in different patients’ population –8. MurthHybrid PET/CT, in addition to the evaluation of absolute MBF and MPR, is able to provide not only functional but also morphological information for the assessment of coronary status, such as quantification of the fat depot and CAC score measurement , 30.Assante et al.  in a patOur study could have clinical implications. First, considering that it remains unclear which are the processes involved in the higher risk of events of patients with RH compared to those with CH, evaluation of MPR could be useful to evaluate the effects of BP on coronary function. Second, a non-invasive measurement of coronary vascular function in patients with RH may help in identifying subjects with a higher cardiac risk acceleration over time, for whom a different therapeutic approach would be hypothesized. This study also has some limitations. In particular, despite the study population selected did not present a history of CAD and showed absence of myocardial perfusion abnormalities, angiographic data were not available. Thus, a possible role of coronary stenosis on reduced MPR values cannot be excluded.The highest risk of cardiovascular events is observed in subjects with RH and coronary vascular dysfunction. The findings suggest that the assessment of coronary vascular function may enhance risk stratification in patients with hypertension.


For pediatric patients, the cut-off values for RVOT dimensions included in the “Task Force Criteria” are not appropriate. However, normative values for the RV size and for RVOT dimensions in children exist (A recent review on arrhythmogenic right ventricular cardiomyopathy (ARVC) in pediatric patients highlights the diagnostic challenge and its important therapeutic consequences in this rare disease . ARVC leen exist , 5.We think that normative values for RV size and RVOT dimension , 5 shoulAlso, RV function in pediatric patients is generally well studied, and normative function parameter values exist for relevant echocardiographic variables, such as tricuspid annular plane systolic excursion (TAPSE), tricuspid annular peak systolic velocity (S′), or the subcostal derived TAPSE (S-TAPSE) , 7. FutuRecently, novel diagnostic criteria for arrhythmogenic cardiomyopathy have been proposed, with the incorporation of late gadolinium enhancement (LGE) as a diagnostic criterion . LGE is The currently used “Task Force criteria” were last updated in 2010 (SK-K and MK drafted and edited the manuscript. Both authors approved the manuscript in its current form prior to submission.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Background: T2 mapping is a magnetic resonance imaging technique that can be used to detect myocardial edema and inflammation. However, the focal nature of myocardial inflammation may render conventional 2D approaches suboptimal and make whole-heart isotropic 3D mapping desirable. While self-navigated 3D radial T2 mapping has been demonstrated to work well at a magnetic field strength of 3T, it results in too noisy maps at 1.5T. We therefore implemented a novel respiratory motion-resolved compressed-sensing reconstruction in order to improve the 3D T2 mapping precision and accuracy at 1.5T, and tested this in a heterogeneous patient cohort.Materials and Methods: Nine healthy volunteers and 25 consecutive patients with suspected acute non-ischemic myocardial injury  were included. The free-breathing T2 maps were acquired as three ECG-triggered T2-prepared 3D radial volumes. A respiratory motion-resolved reconstruction was followed by image registration of the respiratory states and pixel-wise T2 mapping. The resulting 3D maps were compared to routine 2D T2 maps. The T2 values of segments with and without late gadolinium enhancement (LGE) were compared in patients.Results: In the healthy volunteers, the myocardial T2 values obtained with the 2D and 3D techniques were similar . Conversely, in patients, T2 values did differ between 2D (46.7 ± 3.6 ms) and 3D techniques . Moreover, with the 2D technique, T2 values of the LGE-positive segments were similar to those of the LGE-negative segments , whereas the 3D technique did show a significant difference .Conclusion: Respiratory motion-registered 3D radial imaging at 1.5T led to accurate isotropic 3D whole-heart T2 maps, both in the healthy volunteers and in a small patient cohort with suspected non-ischemic myocardial injury. Significantly higher T2 values were found in patients as compared to controls in 3D but not in 2D, suggestive of the technique's potential to increase the sensitivity of CMR at earlier stages of disease. Further study will be needed to demonstrate its accuracy. In the myocardium, it increases in the presence of edema, which makes the T2 relaxation time a useful indicator of acute myocardial injury irrespective of its etiology   . T2 mappcarditis , systemicarditis , and sarcarditis .2 mapping techniques . All participants provided written informed consent prior to the procedure and none of them had contraindications for MRI.n = 9, age = 43 ± 7 y, 5(56%) women, To study the baseline relaxation times, healthy volunteers  women, age 49 ± 10 y; Consecutive patients with suspected acute non-ischemic myocardial injury  imaging 7–15 min after injection of 0.1 mmol/kg of gadobutrol .All MR scanning was performed on a 1.5T clinical scanner . All participants underwent routine bSSFP cine imaging to assess cardiac function , routine mapping , and the2 maps were acquired as ECG-triggered Cartesian 2D T2-prepared bSSFP images , and GRAPPA acceleration factor 2. Images were acquired in a short-axis (SAX) orientation at the basal and mid-ventricular level. Since the reconstructed 2D maps were immediately available on the scanner, visibly corrupted maps were re-acquired as per routine protocol.The routine TP images  with rep2 maps were acquired as three ECG-triggered 3D radial bSSFP volumes with a phyllotaxis trajectory : the source images were non-rigidly registered , and λ = 0.25 in a subgroup of n = 6 patients. T2 map sharpness was assessed by fitting a line from the middle of the septal myocardium to the left-ventricular blood pool with a parametrized sigmoid function (T2 (x) = a/(1+ek(b+x)−)+c), where a, b, and c are scaling variables and k is the sharpness   . The sha2 mapping  , and the inter-subject standard deviation obtained with the two techniques were calculated. Since segmental values can strongly vary both due to difference in local disease patterns and precision of the technique, segmental T2 values were only directly compared in the healthy volunteers. In the patients, the segments that were LGE-positive were grouped for comparison with the LGE-negative segments. These values were then compared between the 2D and 3D techniques with paired Student's t-tests with a Bonferroni correction when appropriate, with P < 0.05 considered statistically significant when two quantities were compared. When multiple quantities were compared to one another a one-way ANOVA with a post-hoc Tukey correction for multiple comparisons was used.The visible myocardium in the routine 2D maps and their matching single slices in the 3D volumes were segmented in MATLAB. The Ton (AHA)  were the2 maps in all study subjects. The visual quality of the maps was assessed by two experienced CMR specialists  on a continuous scale from 1 to 10 with a visual analogue  by an experienced reader (KD) was counted for the 3D technique; this analysis could not be performed for the 2D technique, since visually corrupted maps were re-acquired, resulting in analyzable 2D Tanalogue .2 differences between the 2D and 3D techniques in the patients, as well as to assess the inter- and intra-observer agreement for the 3D technique. Trends in these Bland-Altman plots were tested for significance with Spearman's rank correlation.Bland-Altman analyses were performed to assess the T2 maps of the heart were successfully obtained in all subjects  and k = 1.49 ± 0.29 mm−1 (P = 0.34), respectively. Mapping each respiratory-resolved bin first and then averaging these maps as an alternative reconstruction resulted in k = 1.63 ± 0.29 mm−1 (P = 0.40) for the motion-registered T2 mapping. Conversely, the entire patient group resulted in k = 1.71 ± 0.29 mm−1 and k = 1.89 ± 0.40 mm−1 (P = 0.038) for the 3D and 2D techniques respectively, demonstrating the higher sharpness in the 2D technique despite the larger pixel size. This also held true in the healthy volunteers at k = 1.71 ± 0.31 vs. k = 1.98 ± 0.38 mm−1 (P = 0.037).The sharpness measurements in the patient subgroup resulted in k = 1.56±0.22 mmλ = 0.05 . The mot2 values obtained with the 2D and 3D techniques were highly similar at 45.8 ± 1.8 and 46.8 ± 2.9 ms . The segmental T2 values did not significantly differ between the two techniques  were deemed non-diagnostic due to inaccurately registered thin myocardium.In the healthy volunteers, the myocardial T2 relaxation times did differ between the 2D (46.7 ± 3.6 ms) and 3D techniques . When the myocardium was segmented according to the AHA guidelines, the two techniques resulted in significantly different T2 values in the basal-anterior, basal-inferior, mid-inferoseptal and mid-inferior segments . Conversely, the segmental CoV in the patients was significantly lower for the 2D technique in all segments (P ≤ 0.001) except in the mid-anteroseptal segment. Out of the 300 myocardial segments analyzed in the patients, 14  in one patient) were deemed non-diagnostic. A Bland-Altman analysis of the 2D vs. the 3D technique demonstrated that there was a small bias of −3.0 ms (P = 0.11). The patient T2 values as measured with the 2D technique were not significantly different from those in healthy volunteers (P = 0.50), while the difference was significant when measured with the 3D technique (P = 0.04).In the patients, the average myocardial T −3.0 ms . AlthougP ≥ 0.20), and similar confidence intervals (n = 15) showed a higher confidence interval for the 3D technique (P > 0.2). The visual quality score was higher for the 2D maps than for the 3D maps at 9.6 ± 0.4 vs. 7.2 ± 2.1  despite its larger spread in individual T2 values. Both 2D segment groupings were also significantly different from their 3D equivalents (P < 0.001). The Bloch equation simulations indicated that the proposed 3D mapping technique will moderately underestimate (<5%) the T2 relaxation times for high heart rates  agreed well with that obtained in previous 3D T2 mapping studies  different T2 averages in the healthy volunteers with the 2D and 3D techniques most likely also have several origins, such as a different interplay with the T1 relaxation time during the acquisition  with healthy tissue that blunts the signal change and therefore reduces the sensitivity. Even though LGE presence by itself does not directly indicate edema or inflammation, it potentially colocalizes with patches of active disease in patients with an ongoing disease process. Thus, the slightly increased T2 value in LGE+ segments suggests that smaller and isotropic voxels may be more appropriate in patients with potentially focal non-ischemic injury. Nevertheless, a higher sensitivity of 3D T2 mapping would need to be confirmed with a clinical standard method such as positron emission tomography , a 2D respiratory motion correction (instead of the 1D correction), and the addition of patch-based denoising (which improves the apparent SNR) did result in consistent T2 precision  to RH, as well as statutory grant (ST-98) of the Medical University of Gdansk, Poland to KD and HJ.DP and KG are full-time employees of Siemens Healthcare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.