Cardiac visceral fat volume estimation from low-dose chest computed tomography: a study with a designed beating heart phantom

Background: Since 2017, a pilot project for lung cancer screening by chest low dose computed tomography (LDCT) has been implemented in Moscow. Patients to be included into the screening have risk factors for ischemic heart disease (IHD). The association between epicardial adipose tissue (EAT) volume and coronary artery atherosclerosis, IHD, and atrial fibrillation has been demonstrated previously.Aim: To demonstrate the feasibility of LDCTbased EAT volumetry using a dynamic (contracting) heart phantom.Materials and methods: The study was performed with the designed dynamic heart phantom and chest phantom in two stages. At stage I, two adipose tissue pieces were scanned inside and outside the chest phantom using CT and LDCT. At stage II, the dynamic heart phantom was scanned outside and inside the chest phantom. In addition, we scanned the heart phantom with a coronary calcium phantom. The contracting heart phantom was developed within three months. All scans of the phantom were performed within one day. We determined the adipose tissue thresholds in LDCT and the EAT volumetric error with both chest CT and LDCT. Measurements of the adipose tissue volumes were performed by the radiologist twice with semi-automatic software.Results: The results of stage I helped to identify optimal density thresholds for LDCT-based adipose tissue volumetry in lung cancer screening, ranging from -250 HU to -30 HU. The stage II results showed that for all heart phantom scanning variants, the average EAT volumetry error did not exceed 5%, except for the case of contracting heart phantom with added coronary calcium in a chest phantom with body mass index (BMI) 29 (-5.92%). Adding the coronary calcium phantom to the heart phantom in LDCT increased the error by an average of 4% in BMI 23 and BMI 29 chest phantoms.Conclusion: LDCT-based EAT volumetry with fat density threshold from -250 HU to -30 HU is feasible in lung cancer screening, including patients with coronary calcium. However, considering the phantom design, further patient studies, and correlation of EAT volumes between LDCT for lung cancer screening and сoronary CT angiography are required.

TMAO, a seafood-derived molecule, produces diuresis and reduces mortality in heart failure rats

Trimethylamine-oxide (TMAO) is present in seafood which is considered to be beneficial for health. Deep-water animals accumulate TMAO to protect proteins, such as lactate dehydrogenase (LDH), against hydrostatic pressure stress (HPS). We hypothesized that TMAO exerts beneficial effects on the circulatory system and protects cardiac LDH exposed to HPS produced by the contracting heart. Male, Sprague-Dawley and Spontaneously-Hypertensive-Heart-Failure (SHHF) rats were treated orally with either water (control) or TMAO. In vitro, LDH with or without TMAO was exposed to HPS and was evaluated using fluorescence correlation spectroscopy. TMAO-treated rats showed higher diuresis and natriuresis, lower arterial pressure and plasma NT-proBNP. Survival in SHHF-control was 66% vs 100% in SHHF-TMAO. In vitro, exposure of LDH to HPS with or without TMAO did not affect protein structure. In conclusion, TMAO reduced mortality in SHHF, which was associated with diuretic, natriuretic and hypotensive effects. HPS and TMAO did not affect LDH protein structure.

Cardiac Microvascular Disease - A Complex Diagnosis?

Diagnosing microvascular disease in a continuously moving organ like the contracting heart is difficult. Although we have a wide ranch of (non)invasive diagnostic tools available it is still a challenge to reach a solid conclusion. In many patients there is also a combination of risk factors inducing several disease causing mechanisms further obscuring classification strategies. More research will be crucial going form histology to function to determine the position of microvascular disease in patients with unexplained chest pain.

TMAO, a seafood-derived molecule, produces diuresis and reduces mortality in heart failure rats

ABSTRACTBackgroundThere is an ongoing debate whether trimethylamine-oxide (TMAO), a molecule present in seafood and a derivate of microbiota metabolism, is beneficial or harmful for the circulatory system. Interestingly, deep-water animals accumulate TMAO that protects proteins such as lactate dehydrogenase (LDH) against high hydrostatic pressure. We hypothesized that TMAO may benefit the circulatory system by protecting cardiac LDH exposed to hydrostatic stress (HS) produced by contracting heart.Methods and ResultsMale, 6-week-old, Sprague-Dawley (SD, n=40) and Spontaneously-Hypertensive-Heart-Failure (SHHF n=18) rats were divided into either Water or TMAO oral treatment. After 56 weeks, half of Water and TMAO SD rats were given isoprenaline (ISO) to produce catecholamine stress. In vitro, LDH with or without TMAO was exposed to HS (changes in pressure 0-250mmHg x 280min−1) and was evaluated using fluorescence correlation spectroscopy. After 58 weeks of the treatment survival was 100% in SD-Water, SD-TMAO, ISO-TMAO and 90% in ISO-Water. In SHHF-Water survival was 66% vs 100% in SHHF-TMAO. In general, TMAO-treated rats showed higher diuresis and natriuresis. In comparison to SHHF-Water, SHHF-TMAO showed significantly lower diastolic arterial blood pressure, plasma NT-proBNP and expression of angiotensinogen and AT1 receptors in the heart. In separate experiments, intravenous TMAO but not vehicle or urea significantly increased diuresis in SD. In vitro, exposure of LDH to HS with or without TMAO did not affect the protein structure.ConclusionsTMAO reduces mortality in SHHF rats that is associated with diuretic, natriuretic and hypotensive effects. HS produced by the contracting heart is neutral for cardiac LDH structure.

The speed, reflection and intensity of waves propagating in flexible tubes with aneurysm and stenosis: Experimental investigation

A localized stenosis or aneurysm is a discontinuity that presents the pulse wave produced by the contracting heart with a reflection site. However, neither wave speed ( c) in these discontinuities nor the size of reflection in relation to the size of the discontinuity has been adequately studied before. Therefore, the aim of this work is to study the propagation of waves traversing flexible tubes in the presence of aneurysm and stenosis in vitro. We manufactured different sized four stenosis and four aneurysm silicone sections, connected one at a time to a flexible ‘mother’ tube, at the inlet of which a single semi-sinusoidal wave was generated. Pressure and velocity were measured simultaneously 25 cm downstream the inlet of the respective mother tube. The wave speed was measured using the PU-loop method in the mother tube and within each discontinuity using the foot-to-foot technique. The stenosis and aneurysm dimensions and c were used to determine the reflection coefficient ( R) at each discontinuity. Wave intensity analysis was used to determine the size of the reflected wave. The reflection coefficient increased with the increase and decrease in the size of the aneurysm and stenosis, respectively. c increased and decreased within stenosis and aneurysms, respectively, compared to that of the mother tube. Stenosis and aneurysm induced backward compression and expansion waves, respectively; the size of which was related to the size of the reflection coefficient at each discontinuity, increases with smaller stenosis and larger aneurysms. Wave speed is inversely proportional to the size of the discontinuity, exponentially increases with smaller stenosis and aneurysms and always higher in the stenosis. The size of the compression and expansion reflected wave depends on the size of R, increases with larger aneurysms and smaller stenosis.

Cardiac contraction velocity has evolved to match heart rate with body size through variation in β-cardiac myosin sequence

Heart rate and the maximum velocity of contraction of striated muscle are inversely related to species size. As mammals evolve to different sizes, adaptations are required such as slower contracting heart and skeletal muscles. Analysis of the motor domain of β-myosin from 67 mammals from two clades identifies 14 sites, out of 800, strongly associated with body mass (p<0.01) but not with the clade (p>0.05). Nine of these sites were mutated in the human β-myosin to make it resemble the rat sequence. Biochemical analysis revealed that the rat-human β-myosin chimera functioned like the native rat myosin with a two fold increase in both motility and in the rate of ADP release from the actin.myosin cross-bridge (the step that limits contraction velocity). Both clades use the same small set of amino acids to adjust contraction velocity, suggesting a limited number of ways in which velocity can be manipulated.

Abstract 15951: Palmitate, Not Oleate, is the Preferred Fatty Acid for Cardiac Triacylglycerol Synthesis

Introduction: Previous studies using cell culture models identified cyto-toxic effects of palmitate and that supplementation with oleate was protective by redirecting palmitate into triacylglycerol (TAG) stores. However, other cull culture studies reported that diacylglycerol transferase 1 (DGAT1), the last enzyme in TAG synthesis, demonstrated a preference for oleate. At present, it is not clear whether the supply of exogenous fatty acids (FA) to the heart is differentially allocated into the endogenous TAG pool. Therefore, the purpose of the present study is to examine the influence of palmitate and/or oleate on cardiac TAG incorporation. METHODS/RESULTS: Hearts were isolated from DGAT1-transgenic (DGAT) and control littermates (CON) and perfused in Langendorff mode with a mixed substrate buffer consisting of glucose, lactate, insulin, and FAs. The FA supply was varied with 0.2mM of both labeled (13C) and unlabeled (12C) FAs in 4 different experiments: 1) 13C/12C palmitate; 2) 13C/12C oleate; 3) 13C palmitate/12C oleate; 4) 13C oleate/12C palmitate. The incorporation of 13C palmitate or 13C oleate into the TAG pool was monitored by 13C NMR spectroscopy. In CON hearts (n=3), the incorporation of palmitate was ~65% higher than oleate when the perfusate contained a homogenous supply of FA. This was also observed in DGAT hearts (n=4) although the incorporation of both palmitate and oleate was ~75% higher compared to CON (P <0.05). In the presence of oleate, palmitate incorporation decreased 25-30% in both CON and DGAT hearts. In contrast, oleate incorporation was diminished by ~50% and ~100% in CON and DGAT hearts, respectively, in the presence of palmitate. CONCLUSIONS: These data suggest that when palmitate and oleate are provided in equal concentrations, palmitate is more readily utilized in the synthesis of endogenous TAG stores in the heart. Furthermore, although overexpression of DGAT increases both oleate and palmitate incorporation, the DGAT1 enzyme demonstrates a preference for palmitate. These findings provide insight into the relationship between exogenous FA supply and endogenous TAG dynamics in the contracting heart.