High-resolution Doppler Echocardiography Research Articles

Identification of potential biomarkers for predicting the early onset of diabetic cardiomyopathy in a mouse model

Type 2 diabetes (T2D) is characterized by metabolic derangements that cause a shift in substrate preference, inducing cardiac interstitial fibrosis. Interstitial fibrosis plays a key role in aggravating left ventricular diastolic dysfunction (LVDD), which has previously been associated with the asymptomatic onset of heart failure. The latter is responsible for 80% of deaths among diabetic patients and has been termed diabetic cardiomyopathy (DCM). Through in silico prediction and subsequent detection in a leptin receptor-deficient db/db mice model (db/db), we confirmed the presence of previously identified potential biomarkers to detect the early onset of DCM. Differential expression of Lysyl Oxidase Like 2 (LOXL2) and Electron Transfer Flavoprotein Beta Subunit (ETFβ), in both serum and heart tissue of 6–16-week-old db/db mice, correlated with a reduced left-ventricular diastolic dysfunction as assessed by high-resolution Doppler echocardiography. Principal component analysis of the combined biomarkers, LOXL2 and ETFβ, further displayed a significant difference between wild type and db/db mice from as early as 9 weeks of age. Knockdown in H9c2 cells, utilising siRNA of either LOXL2 or ETFβ, revealed a decrease in the expression of Collagen Type I Alpha1 (COL1A1), a marker known to contribute to enhanced myocardial fibrosis. Additionally, receiver-operating curve (ROC) analysis of the proposed diagnostic profile showed that the combination of LOXL2 and ETFβ resulted in an area under the curve (AUC) of 0.813, with a cut-off point of 0.824, thus suggesting the favorable positive predictive power of the model and further supporting the use of LOXL2 and ETFβ as possible early predictive DCM biomarkers.

Arginine therapy in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes.

Purpose of reviewWe would like to inform clinicians that the systematic administration of oral and intravenous l-arginine is therapeutically beneficial and clinically useful for patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), when they maintain plasma arginine concentration at least 168 μmol/l.Recent findingsMELAS is associated with endothelial dysfunction by decreased plasma l-arginine, nitric oxide (NO), and cyclic guanosine monophosphate. Endothelial dysfunction is also evident using flow-mediated vasodilation measurement by high-resolution Doppler echocardiography in the forearm artery in patients with MELAS. l-arginine is known to be an important precursor of NO to normalize the endothelial function in MELAS. In our clinical trial followed by 7 years follow-up study, the systematic administration of l-arginine to patients with MELAS significantly improved the survival curve of patients compared with natural history. Maintaining plasma arginine concentration at least 168 μmol/l may prevent the ictuses through the putative pathophysiologic mechanism and optimal normalization of endothelial dysfunction.SummaryNeither death nor bedriddenness occurred during the 2-year clinical trials, and the latter did not develop during the 7-year follow-up despite the progressively neurodegenerative and eventually life-threatening nature of MELAS. Therapeutic regimen of l-arginine on MELAS may be beneficial and clinically useful for patient care with MELAS.

Cardiac characterization of sgca-null mice using high resolution echocardiography

Limb-girdle muscular dystrophy 2D (LGMD2D) is an inherited myogenic disorder belonging to the group of muscular dystrophies. Sgca-null mouse is a knock-out model of LGMD2D. Little is known about cardiac phenotype characterization in this model at different ages. We conducted a prospective study to characterize cardiac sgca-null mice phenotype using high resolution Doppler echocardiography at different ages. Conventional echocardiography was performed on anesthetised mice using a Vevo 770 (Visualsonics) with 30 MHz cardiac probe. Wild Type (WT) and sgca-null mice were scanned at 13, 15 and 17 months. From M-mode, we measured interventricular septal (IVS) wall thickness, posterior wall (PW) thickness, and end-left ventricular diameter in systolic and diastolic. From the above parameters, we calculated left ventricular (LV) shortening fraction (SF), LV ejection fraction (EF) and LV mass. At age 13 months, PW diastolic thickness was increased in sgca-null mice (0.89±0.14 mm vs 0.73±0.2 mm; P=0.020) and LV mass was higher in sgca-null mice (LV mass 205.2 mg vs 143 mg; P=0.001). We found also dilation of the LV (LVEDD: 4.84 mm vs 4.29 mm; P=0.019) in sgca-null mice. At age 15 months, dilation of the LV (LVEDD: 4.86 mm vs 4 mm; P=0.05) with an increase of the LV mass (165.7 mg vs 127.12; P=0.03) are found in sgca-null mice. At age 17 months, we found a decrease of the PW thickening (17% vs 30%; P=0.036).This work provides echocardiographic insights for the assessment of pharmaceutical therapies in sgca-null mice.

Cardiac Characterization ofmdxMice Using High-Resolution Doppler Echocardiography

Objectives Duchenne muscular dystrophy is an X-linked neuromuscular disorder. The heart is traditionally involved, leading to heart failure. The mdx mouse is a natural animal model of the disease. We conducted a prospective study to analyze left ventricular (LV) function in mdx mice at different ages using high-resolution Doppler echocardiography. Methods Echocardiography was performed with a 30-MHz cardiac probe. Wild-type and mdx mice were scanned at 10 and 12 months. We measured the interventricular septal wall thickness, posterior wall thickness, and LV diameter in systole and diastole. The LV shortening fraction, LV ejection fraction, and LV mass were then calculated. Results At 10 months, the shortening fractions in mdx and wild-type mice were relatively close (29% ± 5% versus 25% ± 4%). We found a significant difference in the posterior wall thickness change (40% ± 12% in mdx versus 28% ± 10% in wild-type; P = .048). The LV mass/body weight ratio was higher in mdx than wild-type mice (3.67 ± 0.25 versus 3.39 ± 0.26; P = .05). At 12 months, the LV mass was elevated in mdx mice compared to wild-type (152 ±16 versus 135 ± 3.7 mg; P = .04). The diastolic posterior wall thickness change was decreased in mdx mice at 12 months compared to wild-type (21% ± 7% versus 33% ± 4%; P = .01). The LV ejection fraction was not statistically different between mdx and wild-type mice (50% ± 6% versus 54% ± 2%). Conclusions Ten-month-old mdx mice had a significantly higher posterior wall thickness than wild-type mice, but it was not significant at 12 months. In 12-month-old mdx mice, the posterior wall thickness change was significantly lower, and the LV mass was significantly higher. These findings indicate the role of LV function in the early stages of Duchenne muscular dystrophy.

Cardiac Characterization of mdx Mice Using High-Resolution Doppler Echocardiography

Duchenne muscular dystrophy is an X-linked neuromuscular disorder. The heart is traditionally involved, leading to heart failure. The mdx mouse is a natural animal model of the disease. We conducted a prospective study to analyze left ventricular (LV) function in mdx mice at different ages using high-resolution Doppler echocardiography. Echocardiography was performed with a 30-MHz cardiac probe. Wild-type and mdx mice were scanned at 10 and 12 months. We measured the interventricular septal wall thickness, posterior wall thickness, and LV diameter in systole and diastole. The LV shortening fraction, LV ejection fraction, and LV mass were then calculated. At 10 months, the shortening fractions in mdx and wild-type mice were relatively close (29% ± 5% versus 25% ± 4%). We found a significant difference in the posterior wall thickness change (40% ± 12% in mdx versus 28% ± 10% in wild-type; P = .048). The LV mass/body weight ratio was higher in mdx than wild-type mice (3.67 ± 0.25 versus 3.39 ± 0.26; P = .05). At 12 months, the LV mass was elevated in mdx mice compared to wild-type (152 ±16 versus 135 ± 3.7 mg; P = .04). The diastolic posterior wall thickness change was decreased in mdx mice at 12 months compared to wild-type (21% ± 7% versus 33% ± 4%; P = .01). The LV ejection fraction was not statistically different between mdx and wild-type mice (50% ± 6% versus 54% ± 2%). Ten-month-old mdx mice had a significantly higher posterior wall thickness than wild-type mice, but it was not significant at 12 months. In 12-month-old mdx mice, the posterior wall thickness change was significantly lower, and the LV mass was significantly higher. These findings indicate the role of LV function in the early stages of Duchenne muscular dystrophy.

Comprehensive recognition of double-site dynamic obstruction in hypertrophic cardiomyopathy by cardiac magnetic resonance and Doppler echocardiography

The noninvasive assessment of the mechanisms that lead to left ventricular outflow obstruction in hypertrophic cardiomyopathy allows the correct clinical management and the most suitable medical or surgical treatment for these patients. We report the case of a male patient affected by hypertrophic obstructive cardiomyopathy, where an uncommon variety of double-site dynamic obstruction was recognized by an integrated evaluation with high-resolution Doppler echocardiography and cardiac magnetic resonance.

Aortic Stiffness, Flow-Mediated Dilatation and Carotid Intima-Media Thickness in Obstructive Sleep Apnea

Background and Objective: Obstructive sleep apnea (OSA) has a critical association with cardiovascular mortality and morbidity. Carotid intima-media thickness (IMT), flow-mediated dilatation (FMD) and aortic stiffness are early signs of atherosclerosis. The presence of subclinical atherosclerosis was assessed in OSA patients using these parameters. Methods: 40 patients with OSA showing an apnea-hypopnea index (AHI) ≧5 (mean age 51.3 ± 9 years, 32 males) and 24 controls (AHI < 5, mean age 51.9 ± 5.2 years, 19 males) were enrolled in the study. In all subjects, polysomnographic examination and recordings were performed during sleep. IMT of the carotid artery, endothelium-dependent/-independent vasodilation of the brachial artery and aortic elastic parameters were investigated using high-resolution Doppler echocardiography. Results: The demographic data of the patients with OSA and controls were not significantly different. Subjects with OSA demonstrated higher values of aortic stiffness (7.1 ± 1.88 vs. 6.42 ± 1.56, respectively) and IMT (0.85 ± 0.13 vs. 0.63 ± 0.11 mm, p = 0.0001, respectively) but lower distensibility (9.47 ± 1.33 vs. 11.8 ± 3.36 cm²/dyn/10⁶) and FMD (4.57 ± 1.3 vs. 6.34 ± 0.83%, p = 0.0001, respectively) than the controls. The respiratory disturbance index correlated positively with aortic stiffness and IMT and negatively with distensibility and FMD. Conclusion: We observed blunted endothelium-dependent dilatation, increased carotid IMT and aortic stiffness in patients with OSA compared with matched control subjects. This is evident in the absence of other diseases, suggesting that OSA is an independent cause of atherosclerosis. These simple and non-invasive methods help to detect subclinical atherosclerosis in OSA.