Mendelian randomization did not support the causal effect of diabetes on aortic diseases.

Observational studies revealed paradoxically inverse associations between diabetes and aortic diseases (aortic aneurysm or aortic dissection), yet the causality remains to be determined. To investigate the causal associations between diabetes and aortic diseases using Mendelian randomization (MR) analyses. Summary-level data for exposures (type 1 diabetes, type 2 diabetes, fasting glucose, fasting insulin, glycated hemoglobin) and outcomes (aortic dissection and aortic aneurysm) were obtained from public genome-wide association study data. The principal analysis was the inverse-variance weighted (IVW) method. Sensitivity analyses were also carried out, including weighted median, MR-Egger, and multivariable MR methods. According to IVW results, type 1 diabetes (odds ratio [OR]: 0.99; 95% confidence interval [CI] 0.93-1.07; P = 0.87), type 2 diabetes (OR: 0.97; 95% CI 0.77-1.20; P = 0.75), fasting glucose (OR: 1.16; 95% CI 0.48-2.84; P = 0.74), fasting insulin (OR: 2.75; 95% CI 0.53-14.26; P = 0.23), or glycated hemoglobin (OR: 0.33; 95% CI 0.09-1.17; P = 0.09) had no causal effect on aortic dissection. Similarly, type 1 diabetes, type 2 diabetes, fasting glucose, fasting insulin, or glycated hemoglobin had no causal effect on aortic aneurysm. Sensitivity analyses revealed consistent results. MR-Egger method and funnel plot yielded no indication of directional pleiotropy. Diabetes had no causal associations with aortic dissection or aortic aneurysm. The observed inverse associations in previous cohort studies may be explained by confounding factors or reverse causation.

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.

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.

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.

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.

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.

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.

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.

Transplantation efficacy of autologous bone marrow mesenchymal stem cells combined with atorvastatin for acute myocardial infarction (TEAM-AMI): rationale and design of a randomized, double-blind, placebo-controlled, multi-center, Phase II TEAM-AMI trial.

Aim: To determine the efficacy and safety of intracoronary infusion of autologous bone marrow mesenchymal stem cells (MSCINJ) in combination with intensive atorvastatin (ATV) treatment for patients with anterior ST-segment elevation myocardial infarction-elevation myocardial infarction. Patients & methods: The trial enrolls a total of 100 patients with anterior ST-elevation myocardial infarction. The subjects are randomly assigned (1:1:1:1) to receive routine ATV (20 mg/d) with placebo or MSCsINJ and intensive ATV (80 mg/d) with placebo or MSCsINJ. The primary end point is the absolute change of left ventricular ejection fraction within 12 months. The secondary end points include parameters in cardiac function, remodeling and regeneration, quality of life, biomarkers and clinical outcomes. Results & conclusion: The trial will implicate the essential of cardiac micro-environment improvement ('fertilizing') for cell-based therapy. Clinical Trial Registration: NCT03047772.

Comparison of diagnostic accuracy of stress myocardial perfusion imaging for detecting hemodynamically significant coronary artery disease between cardiac magnetic resonance and nuclear medical imaging: A meta-analysis.

AIMS: This study aimed to compare the diagnostic accuracy of stress myocardial perfusion imaging between cardiac magnetic resonance (CMR) and nuclear medical imaging, including single-photon emission computed tomography (SPECT) and positron emission tomography (PET), for the diagnosis of hemodynamically significant coronary artery disease (CAD) with fractional flow reserve (FFR) as the reference standard. METHODS AND RESULTS: We searched PubMed and Embase for all published studies that evaluated the diagnostic accuracy of stress myocardial perfusion imaging modalities, including CMR, SPECT, and PET, to diagnose hemodynamically significant CAD with FFR as the reference standard. A total of 28 articles met the inclusion criteria and were included in the meta-analysis: 14 CMR, 13 SPECT, and 5 PET articles. The results demonstrated a pooled sensitivity of 0.88 (95% confidence interval [CI]: 0.80-0.93), 0.69 (95% CI: 0.56-0.79), and 0.83 (95% CI: 0.70-0.91), and a pooled specificity of 0.89 (95% CI: 0.85-0.93), 0.85 (95% CI, 0.80-0.89), and 0.89 (95% CI, 0.86-0.91) for CMR, SPECT, and PET, respectively. The area under the curve (AUC) of CMR, PET, and SPECT was 0.94 (95% CI, 0.92-0.96), 0.92 (95% CI, 0.89-0.94), and 0.87 (95% CI, 0.83-0.89), respectively. CONCLUSIONS: CMR and PET both have high accuracy and SPECT has moderate accuracy to detect hemodynamically significant CAD with FFR as the reference standard. Furthermore, the diagnostic accuracy of CMR at 3.0 T is superior to 1.5 T.

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.

Assessment of left ventricular twist mechanics by speckle tracking echocardiography reveals association between LV twist and myocardial fibrosis in patients with hypertrophic cardiomyopathy.

We aimed to investigate whether left ventricular (LV) twist analysis can detect the extent of myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM). This prospective case-control study recruited 81 consecutive patients with HCM examined between January 2012 and April 2013. Data of 76 patients were analyzed after excluding 5 patients whose echocardiographic images were of poor quality. Healthy volunteers (n = 46) served as controls. Both groups underwent comprehensive echocardiographic examination (i.e., Bas-Rotation, AP-Rotation, LVEF, LADs, IVST, LAVi, E/Em, LVMI, advanced LV-twist analysis by speckle tracking echocardiography) and magnetic resonance imaging. Between-group differences were analyzed by independent t test; logistic regression analysis was performed to identify effect factors. No significant differences were found between baseline characteristics of HCM and control groups (all p > 0.05). HCM patients had significantly higher Bas-Rotation, AP-Rotation, LV Twist, LVEF, LADs, IVST, LAVi, E/Em and LVMI than controls (all p < 0.0001) and significantly lower LVDd and E/A (both p < 0.001). Bas-Rotation, AP-Rotation, LV-Twist, LADs, IVST, LAVi, E/Em and LVMI were significantly higher in HCM patients with fibrosis than in those without fibrosis (p < 0.001), but no significant differences in other echocardiographic parameters were found between those with and without fibrosis. Age, Bas-Rotation, AP-Rotation, LV twist, LADs, IVST, LAVi, E/A, E/Em, and LVMI were significant effect factors for fibrosis. AUROC analysis showed that LV twist had high discriminatory power to detect extent of myocardial fibrosis (AUC 0.996, 95 % CI 0.989-1.004, p < 0.001). Left ventricular twist mechanics are associated with the extent of myocardial fibrosis. LV-twist assessment by STE may be clinically useful.

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.

Myocardial scar identified by magnetic resonance imaging can predict left ventricular functional improvement after coronary artery bypass grafting.

BACKGROUND: Previous studies have shown that viable myocardium predicts recovery of left ventricular (LV) dysfunction after revascularization. Our aim was to evaluate the prognostic value of myocardial scar assessed by late gadolinium-enhanced cardiovascular magnetic resonance imaging (LGE-CMR) on functional recovery in patients undergoing coronary artery bypass grafting (CABG). METHODS: From November 2009 to September 2012, 63 patients with reduced left ventricular ejection fraction (LVEF) referred for first-time isolated CABG were prospectively enrolled, 52 were included in final analysis. LV functional parameters and scar tissue were assessed by LGE-CMR at baseline and 6 months after surgery. Patency of grafts was evaluated by computed tomography angiography (CTA) 6 months post-CABG. Predictors for global functional recovery were analyzed. RESULTS: The baseline LVEF was 32.7 ± 9.2%, which improved to 41.6 ± 11.0% 6 months later and 32/52 patients improved LVEF by ≥ 5%. Multivariate logistic regression analysis showed that the most significant negative predictor for global functional recovery was the number of scar segments (Odds ratio 2.864, 95% Confidence Interval 1.172-6.996, p = 0.021). Receiver-Operator-Characteristic (ROC) analysis demonstrated that ≤ 4 scar segments predicted global functional recovery with a sensitivity and specificity of 85.0% and 87.5%, respectively (AUC = 0.91, p<0.001). Comparison of ROC curves also indicated that scar tissue was superior to viable myocardium in predicting cardiac functional recovery (p<0.001). CONCLUSIONS: Our findings indicated that scar tissue on LGE-CMR is an independent negative predictor of cardiac functional recovery in patients with impaired LV function undergoing CABG. These observations may be helpful for clinicians and cardiovascular surgeons to determine which patients are most likely to benefit from surgical revascularization.

Atorvastatin enhance efficacy of mesenchymal stem cells treatment for swine myocardial infarction via activation of nitric oxide synthase.

BACKGROUND: In a swine model of acute myocardial infarction (AMI), Statins can enhance the therapeutic efficacy of mesenchymal stem cell (MSCs) transplantation. However, the mechanisms remain unclear. This study aims at assessing whether atorvastatin (Ator) facilitates the effects of MSCs through activation of nitric oxide synthase (NOS), especially endothelial nitric oxide synthase (eNOS), which is known to protect against ischemic injury. METHODS AND RESULTS: 42 miniswines were randomized into six groups (n = 7/group): Sham operation; AMI control; Ator only; MSC only, Ator+MSCs and Ator+MSCs+NG-nitrol-L-arginine (L-NNA), an inhibitor of NOS. In an open-heart surgery, swine coronary artery ligation and reperfusion model were established, and autologous bone-marrow MSCs were injected intramyocardium. Four weeks after transplantation, compared with the control group, Ator+MSCs animals exhibited decreased defect areas of both "perfusion" defined by Single-Photon Emission Computed Tomography (-6.2±1.8% vs. 2.0±5.1%, P = 0.0001) and "metabolism" defined by Positron Emission Tomography (-3.00±1.41% vs. 4.20±4.09%, P = 0.0004); Ejection fraction by Magnetic Resonance Imaging increased substantially (14.22±12.8% vs. 1.64±2.64%, P = 0.019). In addition, indices of inflammation, fibrosis, and apoptosis were reduced and survivals of MSCs or MSC-derived cells were increased in Ator+MSCs animals. In Ator or MSCs alone group, perfusion, metabolism, inflammation, fibrosis or apoptosis were reduced but there were no benefits in terms of heart function and cell survival. Furthermore, the above benefits of Ator+MSCs treatment could be partially blocked by L-NNA. CONCLUSIONS: Atorvastatin facilitates survival of implanted MSCs, improves function and morphology of infarcted hearts, mediated by activation of eNOS and alleviated by NOS inhibitor. The data reveal the cellular and molecular mechanism for anti-AMI therapy with a combination of statin and stem cells.

[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.

[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.