Subendocardial Involvement as an Underrecognized Cardiac MRI Phenotype in Myocarditis.

Background Subendocardial late gadolinium enhancement (LGE) detected with cardiac MRI in myocarditis represents a diagnostic dilemma, since it may resemble myocardial ischemia. Purpose To explore and compare the histopathologic characteristics and clinical features and outcomes in patients with myocarditis with and without subendocardial involvement at cardiac MRI. Materials and Methods This retrospective study evaluated 39 patients with myocarditis pathologically proven by means of either endomyocardial biopsy or explant pathologic findings between 2015 and 2020. Patients were divided into two groups according to cardiac MRI phenotype: 18 with subendocardial involvement (mean age ± standard deviation, 40 years ± 17; 10 women) and 21 with no subendocardial involvement (mean age, 35 years ± 11; six women). The median follow-up period was 784 days (interquartile range [IQR], 90-1123 days). The Student t test, Mann-Whitney U test, and univariable Cox regression were used for statistical analyses. Results In the 18 patients with subendocardial involvement, 12 (67%) had lymphocytic myocarditis and six (33%) had giant cell myocarditis. Patients with subendocardial involvement compared with those without subendocardial involvement had lower left ventricular ejection fraction (mean ± standard deviation, 27% ± 11 vs 41% ± 19; P = .004), larger LGE extent (median, 13% [IQR, 10%-22%] vs 5% [IQR, 2%-17%]; P < .001), higher rates of cardiac death or transplant (eight of 18 patients [44%] vs one of 21 patients [4.8%]; P = .006), higher probability of giant cell myocarditis (six of 18 [33%] vs one of 21 [4.8%]; P = .02), and more major adverse cardiovascular events (MACE) (15 of 18 [83%] vs seven of 21 [33%]; P = .002). In a subgroup of patients with comparable LGE extent (median, 15% vs 16%; P = .40) and left ventricular ejection fraction (median, 27% vs 31%; P = .26), the prognostic difference in terms of MACE remained (15 of 17 patients [88%] vs five of 10 [50%]; P = .02). Conclusion Subendocardial involvement detected with cardiac MRI in myocarditis indicated more severe clinical features, including a higher frequency of severe lymphocytic myocarditis or giant cell myocarditis and worse prognosis. © RSNA, 2021 See also the editorial by de Roos in this issue.

Enhanced laccase production by mutagenized Myrothecium verrucaria using corn stover as a carbon source and its potential in the degradation of 2-chlorophen.

Chlorophenols are widely used in industry and are known environmental pollutants. The degradation of chlorophenols is important for environmental remediation. In this study, we evaluated the biodegradation of 2-chlorophenol using crude laccase produced by Myrothecium verrucaria. Atmospheric and room temperature plasma technology was used to increase laccase production. The culture conditions of the M-6 mutant were optimized. Our results showed that corn stover could replace glucose as a carbon source and promote laccase production. The maximum laccase activity of 30.08 U/mL was achieved after optimization, which was a 19.04-fold increase. The biodegradation rate of 2-chlorophenol using crude laccase was 97.13%, a positive correlation was determined between laccase activity and degradation rate. The toxicity of 2-CP was substantially reduced after degradation by laccase solution. Our findings show the feasibility of the use of corn stover in laccase production by M. verrucaria mutant and the subsequent biodegradation of 2-chlorophenol using crude laccase.

Relationship of myocardial hibernation, scar, and angiographic collateral flow in ischemic cardiomyopathy with coronary chronic total occlusion.

BACKGROUND: The relationship between myocardial viability and angiographic collateral flow is not fully elucidated in ischemic cardiomyopathy (ICM) with coronary artery chronic total occlusion (CTO). We aimed to clarify the relationship between myocardial hibernation, myocardial scar, and angiographic collateral flow in these patients. METHODS AND RESULTS: Seventy-one consecutive ICM patients with 122 CTOs and 652 dysfunctional segments within CTO territories were retrospectively analyzed. Myocardial hibernation (perfusion-metabolism mismatch) and the extent of 18F-fluorodeoxyglucose (FDG) abnormalities were assessed using 99mTc-sestamibi and 18F-FDG imaging. Myocardial scar was evaluated by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging. Collateral flow observed on coronary angiography was assessed using Rentrop classification. In these patients, neither the extent nor frequency of myocardial hibernation or scar was related to the status of collateral flow. Moreover, the matching rate in determining myocardial viability was poor between any 2 imaging indices. The extent of 18F-FDG abnormalities was linearly related to the extent of LGE rather than myocardial hibernation. Of note, nearly one-third (30.4%) of segments with transmural scar still had hibernating tissue. Hibernation and non-transmural scar had higher sensitivity (63.0% and 66.7%) than collateral flow (37.0%) in predicting global functional improvement. CONCLUSIONS: Angiographic collateral cannot accurately predict myocardial viability, and has lower sensitivity in prediction of functional improvement in CTO territories in ICM patients. Hence, assessment of myocardial viability with non-invasive imaging modalities is of importance. Moreover, due to the lack of correlation between myocardial hibernation and scar, these two indices are complementary but not interchangeable.

Abnormalities of myocardial perfusion and glucose metabolism in patients with isolated left ventricular non-compaction.

BACKGROUND: The prevalence of myocardial perfusion and glucose metabolic abnormalities and their significance in patients with isolated left ventricular non-compaction (ILVNC) have not been well investigated. METHODS: Seventeen ILVNC patients who underwent cardiac magnetic resonance (CMR) and (99m)Tc-sestamibi SPECT/fluorine-18 deoxyglucose ((18)F-FDG) PET imaging were included. Left ventricular non-compaction, regional wall motion abnormalities, left ventricular ejection fraction (LVEF), and delayed enhancement (DE) were estimated using CMR. Myocardial perfusion and metabolism were evaluated with SPECT/PET. RESULTS: Ninety-five (32.9%) segments were considered non-compacted. DE was present in 52 (18.0%) segments and 10 (58.8%) patients. The rate of occurrence of DE was significantly higher in compacted segments than in non-compacted segments (22.7% vs 8.4%, P = .003). Myocardial perfusion abnormalities were present in 92 (31.8%) segments, of which 66 were perfusion/metabolism match and 26 were perfusion/metabolism mismatch. The rate of occurrence of perfusion abnormality was similar between compacted and non-compacted segments (32.0% vs 31.6%, P = .948), but it was significantly higher in segments with DE than in those without DE (51.9% vs 27.4%, P = .001). None of the imaging features alone (non-compaction, DE, perfusion abnormalities, match or mismatch) showed significant correlations with LVEF (all P > .05). CONCLUSION: In the current study, myocardial perfusion/metabolism mismatch and match were observed in both non-compacted and compacted myocardium in ILVNC patients. Further research is warranted to determine their pathologic and clinical significance.

Causal effect of hypertension and blood pressure on aortic diseases: evidence from Mendelian randomization.

Hypertension or elevated blood pressure was documented to be an important risk factor for aortic diseases in observational studies, yet the causality remains to be determined. By applying a two-sample Mendelian randomization (MR) approach, we aim to determine whether hypertension or elevated blood pressure (systolic blood pressure [SBP] or diastolic blood pressure [DBP]) is linked causally to aortic aneurysm or aortic dissection. Genetic instruments and summary statistics for hypertension and aortic diseases were obtained from large genome-wide association studies. The traditional inverse variance weighted (IVW) method was used to obtain the causal estimates. Sensitivity analyses including MR-Egger, weighted median and multivariable MR were also performed. Our results suggested that genetic liability to hypertension was associated with aortic dissection (odds ratio [OR]: 1.81; 95% confidence interval [CI]: 1.27-2.58; P = 1.13 × 10-3) and aortic aneurysm (OR: 1.43; 95% CI: 1.22-1.66; P = 7.79 × 10-6). Per standard deviation increase in genetically-determined DBP was significantly associated with increased aortic dissection (OR: 1.14; 95% CI: 1.09-1.19; P = 1.58 × 10-9) and aortic aneurysm (OR: 1.07; 95% CI: 1.05-1.09; P = 8.37 × 10-14). There was a null association between SBP and aortic dissection (OR: 1.01; 95% CI: 0.99-1.94; P = 0.38) or aortic aneurysm (OR: 1.00; 95% CI: 0.99-1.01; P = 0.92). Sensitivity analyses documented similar results. Therefore, hypertension and elevated DBP are causally associated with higher risks of aortic aneurysm and aortic dissection. Preventive interventions for aortic diseases may consider individuals with hypertension, especially those with higher DBP. Meanwhile, further research is required to determine the mechanisms underlying the significantly greater correlation between DBP and aortic diseases than SBP.

Beneficial Effect of Toxoplasma gondii Infection on the Prognosis of Breast Cancer Was Modified by Cytokines.

Background: Animal experiments have shown the anticancer activity of Toxoplasma gondii (T. gondii), but its effect on the prognosis of cancer patients is unclear. Thus, the present study aimed to investigate the prognostic role of anti-T. gondii IgG in breast cancer patients and the modification effect of cytokines. Methods: A total of 1121 breast cancer patients were recruited between 2008 and 2018 and followed up until December 31, 2021. Anti-T. gondii IgG and cytokines were measured using an enzyme-linked immunosorbent assay (ELISA) kit and a multiplex assay platform. Endpoints were overall survival (OS) and progression-free survival (PFS). Survival and multiplicative interaction analyses were performed using multivariate Cox regression models. Results: According to the cutoff value of optical density (OD=0.111), 900 (80.29%) and 221 (19.71%) patients were divided into two groups: low or high anti-T. gondii IgG. Compared to patients with a low anti-T. gondii IgG level, the adjusted hazard ratios (HRs) of OS and PFS for patients with high anti-T. gondii IgG levels were 0.60 (95% confidence interval (CI): 0.37-0.99) and 0.67 (0.46-0.98), respectively. These associations were profound among patients with a high cytokine score (HR=0.29, 95% CI: 0.10-0.82 for OS; HR=0.30, 95% CI: 0.13-0.69 for PFS), accompanied by a significant interaction between the level of anti-T. gondii IgG and the cytokine score (P interaction=0.019 for PFS); interleukin-17 (IL-17) and interleukin-9 (IL-9) were the main contributors to the interaction. Conclusion: Anti-T. gondii IgG was found to be beneficial to breast cancer survival, especially in women with systematic inflammation and high IL-17 or IL-9 levels, suggesting the potential of T. gondii as a prognostic marker and a novel immunotherapy approach for cancer patients.

Apical aneurysm formation in apical hypertrophic cardiomyopathy: Pilot study with cardiac magnetic resonance.

BACKGROUND: The dynamic changes and apical aneurysm formation in apical hypertrophic cardiomyopathy (HCM) have not been specifically described. This study aimed to describe these changes to better understand the progression of apical HCM. METHODS AND RESULTS: Seventy-two patients with apical HCM who underwent at least two cardiac magnetic resonance (CMR) examinations were retrospectively included in this study. The mean interval between the first and last CMR examinations was 50.1 ± 26.8 months (ranging from 4 to 118 months). Compared with the initial values, the left atrial diameter, maximum left ventricular wall thickness and late gadolinium enhancement extent significantly increased (all P < 0.05), while the left ventricular ejection fraction significantly decreased (P < 0.05), at the latest CMR examination. More importantly, the dynamic process of apical aneurysm formation in apical HCM was observed in a subset of patients, which may follow these four stages: starting with systolic apical cavity obliteration, then broadening of the apical slit in systole, further developing into an apical outpouching, and finally forming an apical aneurysm. Eleven patients experienced adverse cardiovascular events, including new-onset or progressive atrial fibrillation (n = 7), hospitalization with heart failure (n = 3) and implantable cardioverter defibrillator intervention (n = 1), at the time of the latest CMR examination. CONCLUSIONS: In the progression of apical HCM, cardiac structure and function will change accordingly. Apical aneurysm formation in apical HCM is a chronic and continuous dynamic process that may follow a 4-step pathway of disease progression.

Multimodality imaging of cor triatriatum dexter complicated with hypertrophic cardiomyopathy of restrictive phenotype.

Cor triatriatum dexter (CTD) is an extremely rare congenital cardiac malformation in which a membrane divides the right atrium into 2 chambers. Hypertrophic cardiomyopathy (HCM) with restrictive phenotype is also a rare cardiomyopathy. We report a case with an 18-year history of chest discomfort, fatigue and syncope following intense physical activity was finally diagnosed with CTD complicated with HCM, and the HCM is a special type, restrictive phenotype. Multimodal imaging was used to diagnose this complex disease and analyzed the main cause of her heart failure, which provided accurate evidence for clinical treatment and prognosis.

[Clinical characteristics of fat replacement of left ventricular myocardium].

OBJECTIVE: To evaluate the clinical characteristics of left ventricular fat replacement. METHODS: We identified 45 patients [28M/17F, mean age (51.9 ± 14.7) years] with left ventricular myocardial fat replacement (CT value ≤ -30 Hu) by cardiovascular CT. RESULTS: Among 45 patients, 25 patients [20M/5F, mean age (61.2 ± 10.4) years]were diagnosed as coronary artery disease (CAD). There was 56%single-vessel disease, 20% double-vessel disease and 24%triple-vessel disease, true left ventricular aneurysm was detected in 3 patients and left ventricular thrombi in 1 patient, the dimension of left ventricle was (54.5 ± 9.4) mm and the LVEF was (51.8 ± 13)% in CAD group. In this group, fat replacement occurred in the region of myocardial infarction and presented as curvilinear band in subendocardial region. The left ventricular wall thickness was lower than 5 mm in 21 cases. The location of fat replacement in CAD group is as follows: apical region in 18 patients, distal septal in 15 patients, distal anterior in 11 patients, mid-septal in 7 patients, mid-anterior in 7 patients and basal in 1 patients. The age of remaining 20 patients (8M/12F) without CAD were (57.8 ± 13.3) years. In the group of non-CAD, dilated cardiomyopathy was diagnosed in 3 patients, atrial septal defect in 1 patient, rheumatic heart disease in 1 patient, there was no structural heart disease in the remaining 15 patients. The dimension of left ventricle was (51.1 ± 9.1) mm and the LVEF was (59.4 ± 13.9)%. In non-CAD group, fat replacement mainly occurred in septal region, presented as curvilinear band in 17 patients and patch in 3 patients. The location of fat replacement in this group is as follows: mid-septal region in 11 patients, distal-septal in 10 patients and apical in 9 patients. The intramural fat replacement was detected in 14 patients: subendocardial fat replacement in 10 patients and both intramural and subendocardial fat replacement in 4 patients. CONCLUSIONS: Left ventricular fat replacement could be documented in CAD patients, non-CAD cardiomyopathy patients and in patients without structural heart disease. Left ventricular fat replacement often positioned in apical region in CAD patients as a consequence of infarct healing while mostly positioned in septal region in non-CAD patients, the definite clinical implication of left ventricular fat replacement in non-CAD patients remains to be clarified.

[Differentiation of true from false left ventricular aneurysm with magnetic resonance imaging in patients after myocardial infarction].

OBJECTIVE: To observe the value of cardiac magnetic resonance imaging (MRI) for differentiation of true from false left ventricular aneurysm in patients after myocardial infraction (MI). METHODS: Twenty-six patients [22 males/4 females, mean age (59.3 ± 9.3) years] with left ventricular aneurysm after MI were imaged with MRI, echocardiography and coronary angiography. The respective findings were compared with surgical pathology results. RESULTS: There were 24 patients with dyspnea and 15 patients with hypertension. LVEF measured by echocardiography was 36.9% ± 9.1% in this patient cohort. Cardiac MRI showed that the left ventricular end diastolic wall thickness was thinner than 5.5 mm in 24 cases, and between 5.5 to 8 mm in 2 cases. The dimension of left ventricle was (67.8 ± 9.3) mm. Dyskinesia presented in 24 cases, and akinesia in 2 cases. Delayed enhancement was shown in all cases by MRI. Cardiac MRI detected left ventricular true aneurysm in 23 cases, false aneurysm in 3 case and left ventricular thrombi in 7 cases. The diagnosis by magnetic resonance imaging corresponded well to pathological findings. Echocardiography misdiagnosed pseudoaneurysm in 1 patient, and failed to detected left ventricular thrombi in 2 cases. CONCLUSION: Cardiac MRI could correctly differentiate true from false left ventricular aneurysm in patients after MI.

[Incidence of coronary artery disease and outcome of patients with left ventricular noncompaction].

OBJECTIVE: To analyze the incidence of coronary artery disease (CAD) and outcome of patients with left ventricular noncompaction (LVNC). METHODS: Fifty-one patients with LVNC evaluated by echocardiography and/or cardiac magnetic resonance (CMR) from January 2006 to August 2010 were retrospectively reviewed. Coronary angiography or MDCT was performed for detecting coronary artery disease. Predictors of the cardiac events were analyzed by Cox regression analysis. RESULTS: There were 31 LVNC patients without CAD and 20 LVNC patients with CAD including single vessel coronary disease in 9 cases, double vessel coronary disease in 3 cases, three vessel coronary disease in 5 cases and left main coronary disease in 3 cases. Coronary artery bypass graft and percutaneous coronary intervention (PCI) were performed in 4 patients. Compared to LVNC patients without CAD, mean age (P = 0.008), incidence of hypertension (65.0% vs. 19.4%, P = 0.001), diabetes mellitus (40.0% vs. 12.9%, P = 0.026) and hyperlipidemia (55.0% vs. 25.8%, P = 0.035) were significantly higher while NT-proBNP level was significantly lower (P = 0.049) in LVNC patients with CAD. Incidence of major cardiac events was similar in LVNC patients with or without CAD. LogNT-proBNP is the independent prognostic factor for adverse cardiac events in patients with LVNC (HR 3.993, 95%CI 1.140 - 13.988, P = 0.030). CONCLUSIONS: Coronary artery disease is common in patients with LVNC and associated with traditional risk factors for CAD. Poor prognosis is associated with increased NT-proBNP but not with CAD in this patient cohort.

[In vivo re-distribution of intra-coronary transplanted stem cells into beating and arrested hearts by magnetic resonance imaging in an acute myocardial infarction swine model].

OBJECTIVE: To analyze the stem cell re-distribution after intra-coronary infusion (ICI) into arrested and beating hearts in a swine myocardial infarction (MI) model using magnetic resonance imaging (MRI). METHODS: Bone marrow-derived mesenchymal stem cells were obtained from male swine and labeled with iron oxide during culture. One week after MI in female swine, the survivors were randomly divided into 4 groups. Cardiopulmonary bypass was set up to arrest the heart, and then SPIO labeled male stem cells (1 × 10(8)) were infused through coronary of beating heart (n = 6) and the arrested heart (n = 6). Saline was injected in either the beating or arresting heart as respective controls. Three days later, cell distribution was assessed by T2(*) change with magnetic resonance imaging and Y-chromosome (SRY) was detected with quantitative polymerase chain reaction. RESULTS: The reduction of T2(*) values was significantly different in the hearts, spleens, livers and lung between the transplantation groups and the control groups. Only few transplanted cells were localized in the heart and T2(*) values were similar between beating and arrest heart groups [(-7.81 ± 2.03) ms vs. (-6.56 ± 1.72) ms, P > 0.05], while T2(*) value reduction was more significant in the spleen and liver in arrest heart group than in beating heart group [spleen: (-16.72 ± 2.83) ms vs. (-22.18 ± 3.98) ms, P < 0.01, liver: (-2.40 ± 0.44) ms vs. (-5.32 ± 3.40) ms, P < 0.05]. T2(*) value was similar in kidney among the four groups. qRT-PCR detected SRY gene was similar in the heart, less in the spleen and liver while more in the lung in beating heart group compared to arrested heart group. In vitro Prussian blue stained positively transplanted cells were found in the above organs in transplantation group. CONCLUSIONS: The majority of stem cells transplanted by ICI would be entrapped by the extracardiac organs. Stem cell transplantation via ICI into the arrested heart does not favor more cells retention in the injured myocardium. Further investigation is needed to optimize the approach of stem cell delivery.

[Comparison of clinical and MRI features between dilated cardiomyopathy and left ventricular noncompaction].

OBJECTIVE: To characterize the clinical and cardiac MRI features of dilated cardiomyopathy (DCM) and left ventricular noncompaction (LVNC). METHODS: Compared the clinical and MRI features between 25 patients with LVNC and 21 patients with DCM. The MRI derived diastolic left ventricular wall thickness and the number and degree of noncompaction (NC) were evaluated using the 17-segment model. RESULTS: Chest distress, shortness of breath and abnormal ECG were presented in all DCM patients, abnormal ECG was evidenced in 22 LVNC patients and 21 out of 25 LVNC patients presented similar clinical symptoms as DCM patients while the rest 4 LVNC patients were asymptomatic. Left atrial and ventricular dimensions were significantly smaller in LVNC patients compared to DCM patients. The degree of left ventricular (LV) spherical remodeling was significantly greater in patients with DCM (sphericity index, SI = 0.81 +/- 0.06) than in patients with LVNC (SI = 0.74 +/- 0.11, P < 0.05). The LV ejection fraction (LVEF) was significantly higher in patients with LVNC (32.7% +/- 14.2%) than that in patients with DCM (15.0% +/- 5.1%). The number of NC segments in LVNC patients (9 +/- 1) was significantly higher than the number of hypertrabeculation segment in DCM patients (5 +/- 2). The left ventricular apex (the 17th segment) was unexceptionally involved in all LVNC patients, while hypertrabeculation was absent in the 17th segment of DCM patients. The NC was more common in the apical and mid segments (16th, 12th and 11th segments) than in basal and mid septal segments (2nd, 3rd, 8th and 9th segments) in both LVNC and DCM patients. The thickness of compacted myocardium of the segments associated with noncompaction appeared thin in two groups. The wall thickness of noncompaction myocardium segments was thicker in LVNC patients than in DCM patients. The end-diastolic NC/C ratio was, on average, higher in patients with LVNC (3.3 +/- 0.6) than in patients with DCM (1.9 +/- 0.3). CONCLUSIONS: The clinical manifestation is similar while there are significant differences in the morphology and function of left atria and left ventricle between the LVNC and DCM patients. The different distribution and degree of NC were helpful to differentiate LVNC from DCM.

[Clinical characteristics and hypertrophic segments distribution of patients with hypertrophic cardiomyopathy].

OBJECTIVE: to analyze the clinical data and hypertrophic segments distribution of patients with hypertrophic cardiomyopathy (HCM). METHODS: clinical data including signs and symptoms, electrocardiogram and echocardiography were collected. All patients were imaged with cardiac magnetic resonance imaging (CMR). RESULTS: from March 2004 to March 2007, 225 consecutive patients [163 males, mean age (50.4 ± 14.5) years] with CMR defined HCM were included in this study, positive familial history was obtained in 73 patients, 50 patients were associated with hypertension, 14 patients with coronary artery disease and 5 patients with diabetes mellitus, 28 patients were asymptomatic, 197 patients were symptomatic, and 11 patients with syncope. Electrocardiogram abnormalities occurred in 216 patients. Systolic murmurs were present in 126 patients. Echocardiography examination evidenced left ventricular outflow obstruction in 95 patients, mitral insufficiency in 32 patients, 32.1% segments were hypertrophied, asymmetrical hypertrophy presented in 222 patients and symmetrical hypertrophy in 3 patients. The left atrial dimension was (39.4 ± 8.3) mm, and left ventricular diastolic dimension was (47.8 ± 5.5) mm in this cohort. Apical hypertrophy occurred in 67 patients. The thickness of ventricular septum was (24.3 ± 5.3) mm in obstructive HCM and (21.6 ± 4.6) mm in non-obstructive HCM (P < 0.05). The thickness of hypertrophy apical segment was (15.6 ± 3.4) mm. CONCLUSIONS: HCM in Chinese patients is characterized by the high prevalence among men and late onset of presentation. Combining clinical, electrocardiogram, echocardiographic and CMR results are of importance for correctly diagnosing HCM in daily practice.

Apical hypertrophic cardiomyopathy with left ventricular apical aneurysm: prevalence, cardiac magnetic resonance characteristics, and prognosis.

AIMS: Hypertrophic cardiomyopathy (HCM) with left ventricular apical aneurysm (LVAA) is associated with an increased risk of adverse cardiovascular events. However, the clinical significance of LVAA in apical HCM (ApHCM) has not been reported. This study aimed to investigate the prevalence, cardiac magnetic resonance (CMR) characteristics, and prognosis of LVAA in ApHCM patients. METHODS AND RESULTS: A total of 1332 consecutive ApHCM patients confirmed by CMR in our hospital were retrospectively analysed. LVAAs were identified in 31 patients of all ApHCM patients (2.3%, 31/1332). Besides, 31 age- and gender-matched ApHCM patients without LVAA were used for comparison. Of the 31 aneurysm patients (mean age, 53.8 ± 15.1 years old), 28 (90.3%) had clinical symptoms, and 3 (9.7%) had a family history of HCM. The rate of missed diagnosis of echocardiography for detecting LVAA was 64.5% (20/31), most (90%, 18/20) of unidentified LVAAs by echocardiography were small aneurysms (<20 mm). Compared with ApHCM patients without LVAA, the proportion of systolic mid-cavity obstruction and late gadolinium enhancement (LGE) presence, and the LGE extent in ApHCM patients with LVAA were significantly higher (all P<0.05). The Kaplan-Meier curves showed that the event-free survival rate in ApHCM patients with LVAA was significantly lower than that in ApHCM patients without LVAA (log rank, P = 0.010). CONCLUSION: ApHCM with LVAA is a very rare condition, which is often missed by echocardiography and could be reliably detected with CMR and is associated with a higher risk of adverse cardiovascular events compared with ApHCM without LVAA.

Pre-existing Health Conditions and Epicardial Adipose Tissue Volume: Potential Risk Factors for Myocardial Injury in COVID-19 Patients.

Background: Myocardial injury is a life-threatening complication of coronavirus disease 2019 (COVID-19). Pre-existing health conditions and early morphological alterations may precipitate cardiac injury and dysfunction after contracting the virus. The current study aimed at assessing potential risk factors for COVID-19 cardiac complications in patients with pre-existing conditions and imaging predictors. Methods and Results: The multi-center, retrospective cohort study consecutively enrolled 400 patients with lab-confirmed COVID-19 in six Chinese hospitals remote to the Wuhan epicenter. Patients were diagnosed with or without the complication of myocardial injury by history and cardiac biomarker Troponin I/T (TnI/T) elevation above the 99th percentile upper reference limit. The majority of COVID-19 patients with myocardial injury exhibited pre-existing health conditions, such as hypertension, diabetes, hypercholesterolemia, and coronary disease. They had increased levels of the inflammatory cytokine interleukin-6 and more in-hospital adverse events (admission to an intensive care unit, invasive mechanical ventilation, or death). Chest CT scan on admission demonstrated that COVID-19 patients with myocardial injury had higher epicardial adipose tissue volume ([EATV] 139.1 (83.8-195.9) vs. 92.6 (76.2-134.4) cm2; P = 0.036). The optimal EATV cut-off value (137.1 cm2) served as a useful factor for assessing myocardial injury, which yielded sensitivity and specificity of 55.0% (95%CI, 32.0-76.2%) and 77.4% (95%CI, 71.6-82.3%) in adverse cardiac events, respectively. Multivariate logistic regression analysis showed that EATV over 137.1 cm2 was a strong independent predictor for myocardial injury in patients with COVID-19 [OR 3.058, (95%CI, 1.032-9.063); P = 0.044]. Conclusions: Augmented EATV on admission chest CT scan, together with the pre-existing health conditions (hypertension, diabetes, and hyperlipidemia) and inflammatory cytokine production, is associated with increased myocardial injury and mortality in COVID-19 patients. Assessment of pre-existing conditions and chest CT scan EATV on admission may provide a threshold point potentially useful for predicting cardiovascular complications of COVID-19.

Strengthening effects of bone marrow mononuclear cells with intensive atorvastatin in acute myocardial infarction.

OBJECTIVE: To test whether intensive atorvastatin (ATV) increases the efficacy of transplantation with autologous bone marrow mononuclear cells (MNCs) in patients suffering from anterior ST-elevated myocardial infarction (STEMI). METHODS: This clinical trial was under a 2×2 factorial design, enrolling 100 STEMI patients, randomly into four groups of regular (RA) or intensive ATV (IA) with MNCs or placebo. The primary endpoint was the change of left ventricular ejection fraction (LVEF) at 1-year follow-up from baseline, primarily assessed by MRI. The secondary endpoints included other parameters of cardiac function, remodelling and regeneration determined by MRI, echocardiography, positron emission tomography (PET) and biomarkers. RESULTS: All the STEMI patients with transplantation of MNCs showed significantly increased LVEF change values than those with placebo (p=0.01) with only in the IA+MNCs patients group demonstrating significantly elevation of LVEF than in the IA+placebo group (+12.6% (95%CI 10.4 to 19.3) vs +5.0% (95%CI 4.0 to 10.0), p=0.001), pointing to a better synergy between ATV and MNCs (p=0.019). PET analysis revealed significantly increased viable areas of myocardium (p=0.015), while the scar sizes (p=0.026) and blood aminoterminal pro-B-type natriuretic peptide (p<0.034) reduced. All these above benefits of MNCs were also attributed to IA+MNCs instead of RA+MNCs group of patients with STEMI. CONCLUSIONS: Intensive ATV treatment augments the therapeutic efficacy of MNCs in patients with anterior STEMI at the convalescent stage. The treatment with the protocol of intensive ATV and MNC combination offers a clinically essential approach for myocardial infarction. TRIAL REGISTRATION NUMBER: NCT00979758.

Evaluation of left ventricular volumes and ejection fraction by gated SPECT and cardiac MRI in patients with dilated cardiomyopathy.

PURPOSE: The goal of this study was to evaluate the accuracy of gated single photon emission computed tomography (SPECT) in the assessment of left ventricular (LV) end-diastolic/end-systolic volumes (EDV, ESV) and ejection fraction (LVEF) in patients with dilated cardiomyopathy, using cardiac magnetic resonance imaging (MRI) as the reference method. Furthermore, software-specific characteristics of Quantitative Gated SPECT (QGS), Emory Cardiac Toolbox (ECTB) and 4D-MSPECT were analysed. METHODS: Thirty-six patients with dilated cardiomyopathy who underwent gated (99m)Tc-methoxyisobutylisonitrile SPECT and cardiac MRI were included. LV EDV, ESV and LVEF values of gated SPECT were calculated using QGS, ECTB and 4D-MSPECT. RESULTS: The correlation between the results of gated SPECT and cardiac MRI was excellent for EDV [R = 0.872 (QGS), R = 0.879 (ECTB), R = 0.869 (4D-MSPECT)], ESV [R = 0.908 (QGS), R = 0.897 (ECTB), R = 0.880 (4D-MSPECT)] and LVEF [R = 0.794 (QGS), R = 0.763 (ECTB), R = 0.710 (4D-MSPECT)]. EDV and ESV assessed by QGS did not differ significantly from those assessed by cardiac MRI (all p = NS), whereas EDV and ESV were overestimated by ECTB and 4D-MSPECT compared with cardiac MRI (all p < 0.05). LVEF was overestimated by QGS, ECTB and 4D-MSPECT compared with cardiac MRI (all p < 0.05). CONCLUSIONS: The correlation between gated SPECT and cardiac MRI is excellent for LV volume and LVEF values calculated by QGS, ECTB and 4D-MSPECT in patients with dilated cardiomyopathy. However, algorithm-varying over- or underestimation of LV volumes and LVEF should be accounted for in the clinical context.

Atorvastatin treatment improves survival and effects of implanted mesenchymal stem cells in post-infarct swine hearts.

AIMS: To investigate whether Atorvastatin (Ator) treatment improves the cardiac micro-environment that facilitates survival and differentiation of bone-marrow-derived mesenchymal stem cells (MSCs) implanted in the post-infarct myocardium. METHODS AND RESULTS: Myocardial infarction was created by coronary ligation and immediately after reperfusion, autologous bone-marrow-derived MSCs were transplanted into the hearts of Chinese swine that were pretreated with or without Ator. Six weeks after transplantation, as evaluated by SPECT and MRI all the animals with Ator showed improved cardiac perfusion and contractility when compared with untreated. Increased survival and differentiation of implanted MSCs and decreased infarct area were observed in the Ator-treated, MSC-implanted animals. In the absence of Ator, MSC transplantation only achieved a modest improvement in perfusion and morphology. The combined treatment with Ator and MSCs significantly inhibited cardiac cell apoptosis, reduced oxidative stress, and suppressed expression of the inflammatory cytokines in the post-infarct myocardium. CONCLUSION: Ator treatment may protect the myocardium undergoing acute infarction and reperfusion by creating a better environment for the survival and differentiation of implanted MSCs. The benefit of the Ator/stem cell combined therapy may result from the statin-mediated inhibition of apoptosis, oxidative stress, and inflammation in the infarcted myocardium.

[Gelatin microspheres containing vascular endothelial growth factor enhances the efficacy of bone marrow mesenchymal stem cells transplantation in a swine model of myocardial infarction.].

OBJECTIVE: To investigate the efficacy of transplantation of mesenchymal stem cells (MSC) with gelatin microspheres containing vascular endothelial growth factor in ischemic regions in infracted swine hearts. METHODS: Twelve Chinese mini swines with infarction were randomized to receive autogenetic MSC injection to the peri-infarction area of left ventricular wall (MSC group, n = 6) or MSC transplantation with gelatin hydrogel microspheres incorporating vascular endothelial growth factor (VEGF-MSC group, n = 6). Three weeks later, left ventricular function was assessed by magnetic resonance imaging (MRI). The contrast of the MSC hypointense lesion was determined using the difference in signal intensity between the hypointense and normal myocardium divided by signal intensity of the normal region. Myocardial capillary density, the number of DAPI positive MSC and the apoptotic MSC were also determined. RESULTS: The diameter of the microspheres averaged (104.0 +/- 22.6) microm. At 24 hours after transplantation, MSC were identified by MRI as large intramyocardial signal voids at injection sites which persisted up to 3 weeks. There was no significant difference in the contrast of the lesions and in the size of the lesions at 24 hours between two groups. At 3 weeks after injection, the size of the lesions and the contrast of the lesion were decreased (P < 0.05) in both groups. The capillary density of the injection site was significantly more in the MSC-VEGF microsphere group than that in MSC group [(15.2 +/- 5.4)/HPF vs. (10.2 +/- 5.0)/HPF, t = 2.43, P < 0.05], and there were more dense DAPI labeled MSC per high power fields in injection sites of MSC-VEGF microsphere group than that in MSC group [(354 +/- 83)/HPF vs. (278 +/- 97)/HPF, t = 3.14, P < 0.05]. Moreover, the apoptosis rate of MSCs of MSCs-VEGF microsphere group was less than that of MSC group [(6.4 +/- 4.1)% vs. (11.9 +/- 4.8)%, t = 2.97, P < 0.05]. CONCLUSIONS: MSC transplantation with gelatin hydrogel microspheres incorporating VEGF enhanced the efficacy of MSC in this swine model of myocardial infarction. MRI tracking of MSC is feasible and represents a preferred method for studying the engraftment of MSCs in infracted tissue.