The impact of diabetes mellitus on cardiac function assessed by magnetic resonance imaging in patients with hypertrophic cardiomyopathy.

BACKGROUND: The adverse prognostic impact of diabetes on hypertrophic cardiomyopathy (HCM) is poorly understood. We sought to explore the underlying mechanisms in terms of structural and functional remodelling in HCM patients with coexisting diabetes (HCM-DM). METHODS: A total of 45 HCM-DM patients were retrospectively included. Isolated HCM controls (HCM patients without diabetes) were matched to HCM-DM patients in terms of maximal wall thickness, age, and gender distribution. Left ventricular (LV) and atrial (LA) performance were evaluated using cardiac magnetic resonance feature tracking strain analyses. The associations between diabetes and LV/LA impairment were investigated by univariable and multivariable linear regression. RESULTS: Compared with the isolated HCM controls, the HCM-DM patients had smaller end-diastolic volume and stroke volume, lower ejection fraction, larger mass/volume ratio and impaired strains in all three directions (all P < 0.05). In terms of the LA parameters, HCM-DM patients presented impaired LA reservoir and conduit strain/strain rate (all P < 0.05). Among all HCM patients, comorbidity with diabetes was independently associated with a low LV ejection fraction (ß = - 6.05, P < 0.001) and impaired global longitudinal strain (ß = 1.40, P = 0.007). Moreover, compared with the isolated HCM controls, HCM-DM patients presented with more myocardial fibrosis according to late gadolinium enhancement, which was an independent predictor of impaired LV global radial strain (ß = - 45.81, P = 0.008), LV global circumferential strain (ß = 18.25, P = 0.003), LA reservoir strain (ß = - 59.20, P < 0.001) and strain rate (ß = - 2.90, P = 0.002). CONCLUSIONS: Diabetes has adverse effects on LV and LA function in HCM patients, which may be important contributors to severe manifestations and outcomes in those patients. The present study strengthened the evidence of the prevention and management of diabetes in HCM patients.

Reduced thoracic skeletal muscle size is associated with adverse outcomes in diabetes patients with heart failure and reduced ejection fraction: quantitative analysis of sarcopenia by using cardiac MRI.

BACKGROUND: Sarcopenia is frequently found in patients with heart failure with reduced ejection fraction (HFrEF) and is associated with reduced exercise capacity, poor quality of life and adverse outcomes. Recent evidence suggests that axial thoracic skeletal muscle size could be used as a surrogate to assess sarcopenia in HFrEF. Since diabetes mellitus (DM) is one of the most common comorbidities with HFrEF, we aimed to explore the potential association of axial thoracic skeletal muscle size with left ventricular (LV) remodeling and determine its prognostic significance in this condition. METHODS: A total of 243 diabetes patients with HFrEF were included in this study. Bilateral axial thoracic skeletal muscle size was obtained using cardiac MRI. Patients were stratified by the tertiles of axial thoracic skeletal muscle index (SMI). LV structural and functional indices, as well as amino-terminal pro-B-type natriuretic peptide (NT-proBNP), were measured. The determinants of elevated NT-proBNP were assessed using linear regression analysis. The associations between thoracic SMI and clinical outcomes were assessed using a multivariable Cox proportional hazards model. RESULTS: Patients in the lowest tertile of thoracic SMI displayed a deterioration in LV systolic strain in three components, together with an increase in LV mass and a heavier burden of myocardial fibrosis (all P < 0.05). Moreover, thoracic SMI (ß = -0.25; P < 0.001), rather than body mass index (ß = -0.04; P = 0.55), was independently associated with the level of NT-proBNP. The median follow-up duration was 33.6 months (IQR, 20.4-52.8 months). Patients with adverse outcomes showed a lower thoracic SMI (40.1 [34.3, 47.9] cm2/m2 vs. 45.3 [37.3, 55.0] cm2/m2; P < 0.05) but a similar BMI (P = 0.76) compared with those without adverse outcomes. A higher thoracic SMI indicated a lower risk of adverse outcomes (hazard ratio: 0.96; 95% confidence interval: 0.92-0.99; P = 0.01). CONCLUSIONS: With respect to diabetes patients with HFrEF, thoracic SMI is a novel alternative for evaluating muscle wasting in sarcopenia that can be obtained by a readily available routine cardiac MRI protocol. A reduction in thoracic skeletal muscle size predicts poor outcomes in the context of DM with HFrEF.

A comprehensive review on the recent advances for 5-aminolevulinic acid production by the engineered bacteria.

5-Aminolevulinic acid (5-ALA) is a non-proteinogenic amino acid essential for synthesizing tetrapyrrole compounds, including heme, chlorophyll, cytochrome, and vitamin B12. As a plant growth regulator, 5-ALA is extensively used in agriculture to enhance crop yield and quality. The complexity and low yield of chemical synthesis methods have led to significant interest in the microbial synthesis of 5-ALA. Advanced strategies, including the: enhancement of precursor and cofactor supply, compartmentalization of key enzymes, product transporters engineering, by-product formation reduction, and biosensor-based dynamic regulation, have been implemented in bacteria for 5-ALA production, significantly advancing its industrialization. This article offers a comprehensive review of recent developments in 5-ALA production using engineered bacteria and presents new insights to propel the field forward.

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.

A novel metagenome-derived beta-galactosidase: gene cloning, overexpression, purification and characterization.

A novel beta-galactosidase gene, zd410, was isolated by screening a soil metagenomic library. Sequence analysis revealed that zd410 encodes a protein of 672 amino acids with a predicted molecular weight of 78.6 kDa. The recombinant ZD410 was expressed and purified in Pichia pastoris, with a yield of ca. 300 mg from 1 L culture. The purified enzyme displayed optimal activity at 38 degrees C and pH 7.0. Given that the enzyme had 54% of the maximal activity at 20 degrees C and 11% of the maximal activity at close to 0 degrees C, ZD410 was regarded as a cold-adapted beta-galactosidase. ZD410 displays high enzymatic activity for its synthetic substrate-ONPG (o-nitrophenyl-beta-D-galactopyranoside, 243 U/mg) and its natural substrate-lactose (25.4 U/mg), while its activity was slightly stimulated by addition of Na(+), K(+), or Ca(2+) at low concentrations. ZD410 is a good candidate of beta-galactosidases for food industry after further study.

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.