A Comparative Study of Systolic and Diastolic Mechanical Synchrony in Canine, Primate, and Healthy and Failing Human Hearts.

Aim: Mechanical dyssynchrony (MD) is associated with heart failure (HF) and may be prognostically important in cardiac resynchronization therapy (CRT). Yet, little is known about its patterns in healthy or diseased hearts. We here investigate and compare systolic and diastolic MD in both right (RV) and left ventricles (LV) of canine, primate and healthy and failing human hearts. Methods and Results: RV and LV mechanical function were examined by pulse-wave Doppler in 15 beagle dogs, 59 rhesus monkeys, 100 healthy human subjects and 39 heart failure (HF) patients. This measured RV and LV pre-ejection periods (RVPEP and LVPEP) and diastolic opening times (Q-TVE and Q-MVE). The occurrence of right (RVMDs) and left ventricular systolic mechanical delay (LVMDs) was assessed by comparing RVPEP and LVPEP values. That of right (RVMDd) and left ventricular diastolic mechanical delay (LVMDd) was assessed from the corresponding diastolic opening times (Q-TVE and Q-MVE). These situations were quantified by values of interventricular systolic (IVMDs) and diastolic mechanical delays (IVMDd), represented as positive if the relevant RV mechanical events preceded those in the LV. Healthy hearts in all species examined showed greater LV than RV delay times and therefore positive IVMDs and IVMDd. In contrast a greater proportion of the HF patients showed both markedly increased IVMDs and negative IVMDd, with diastolic mechanical asynchrony negatively correlated with LVEF. Conclusion: The present IVMDs and IVMDd findings have potential clinical implications particularly for personalized setting of parameter values in CRT in individual patients to achieve effective treatment of HF

Comparison of Left Ventricular Global Longitudinal Strain Measured with Real Time Triplane and 2-Dimensional Echocardiography in Patients with Atrial Fibrillation

Background: Left ventricular (LV) global longitudinal peak systolic strain (GLPS, also known as GLS) based on speckle tracking echocardiography (STE) is validated to evaluate global LV systolic function, particularly the global average GLPS (GLPSAvg, which is averaged from three apical longitudinal views). However, its application is limited in atrial fibrillation (AF) due to its variability of cycle lengths. A novel imaging technique, real time triplane echocardiography (3PE), allows simultaneous presentation of apical 4-, 2-, and 3- chamber views within one ultrasonic view. We compared GLPS measures using 3PE and conventional 2-dimensional echocardiography (2DE) in patients with AF. Methods Patients with AF and a control group with sinus rhythm were enrolled prospectively. Three apical sectional GLPSs and GLPSAvg were measured with conventional 2D (2D-STE) and 3PE (3P-STE) modes. Comparison, correlation and agreement of measurements with both modes were made. Ten patients were selected randomly for reproducibility study. Results (1) A total of 39 patients with AF and 38 control subjects were analyzed. Adequate apical 3PE views were acquired in most subjects (95%). Measurement of GLPSs with 3P-STE was more readily available than with 2D-STE in AF group (97.5% vs. 60.0%, P=000). (2) The GLPSs measured with 3P-STE was constantly lower than that of 2D-STE, but linearly correlated, with GLPSAvg revealing the best correlation (r=0.86, P=0.00 in both groups). (3) The reproducibility of GLPS measured by 3P-STE was valid. Conclusions Triplane echocardiography may extend the use of LV global longitudinal strain to patients with AF for assessment of global LV systolic function

The effect of hypertension on cardiac structure and function in different types of hypertrophic cardiomyopathy: A single-center retrospective study

Objectives: To determine whether hypertension (HTN) affects cardiac structure and function in different types of hypertrophic cardiomyopathy (HCM). Design: Patients with obstructive HCM (n = 40), septal HCM (n = 88), and apical HCM (n = 42) were separated into hypertensive and non-hypertensive subgroups, and echocardiographic parameters at baseline and at follow-up were compared between the subgroups. Results: At follow-up, hypertensive obstructive HCM patients showed a decrease in end-diastolic volume (from 93.87 ± 26.08 mL to 79.06 ± 20.07 mL; p= 0.045) and in left ventricular end-diastolic diameter (from 45.00 ± 5.32 mm to 41.83 ± 4.58 mm; p =0.042). Non-hypertensive obstructive HCM patients showed a decrease in maximum aortic velocity (from 2.01 ± 0.53 m/s to 1.28 ± 0.25 m/s; p= 0.011) and in aortic maximum pressure gradient (from 17.22 ± 9.57 mm Hg to 6.79 ± 2.44 mm Hg; p= 0.03). Hypertensive apical HCM patients showed an increase in end-diastolic volume (from 95.28 ± 16.54 mL to 119.74 ± 25.19 mL; p= 0.016) and in left ventricular end-diastolic diameter (from 45.28 ± 3.36 mm to 50.20 ± 4.56 mm; p= 0.007). Conclusions: HTN can affect left ventricular capacity in obstructive HCM and apical HCM, causing a decrease in ventricular capacity in the former and increase in the latter; it has no significant effect on the size of the left ventricular cavity in septal HCM. HTN can lead to a poor therapeutic effect on aortic flow rate and pressure gradient in obstructive HCM patients

In vitro reconstitution guide for targeted synthetic metabolism of chemicals, nutraceuticals and drug precursors

With the developments in metabolic engineering and the emergence of synthetic biology, many breakthroughs in medicinal, biological and chemical products as well as biofuels have been achieved in recent decades. As an important barrier to traditional metabolic engineering, however, the identification of rate-limiting step(s) for the improvement of specific cellular functions is often difficult. Meanwhile, in the case of synthetic biology, more and more BioBricks could be constructed for targeted purposes, but the optimized assembly or engineering of these components for high-efficiency cell factories is still a challenge. Owing to the lack of steady-state kinetic data for overall flux, balancing many multistep biosynthetic pathways is time-consuming and needs vast resources of labor and materials. A strategy called targeted engineering is proposed in an effort to solve this problem. Briefly, a targeted biosynthetic pathway is to be reconstituted in vitro and then the contribution of cofactors, substrates and each enzyme will be analyzed systematically. Next is in vivo engineering or de novo pathway assembly with the guidance of information gained from in vitro assays. To demonstrate its practical application, biosynthesis pathways for the production of important products, e.g. chemicals, nutraceuticals and drug precursors, have been engineered in Escherichia coli and Saccharomyces cerevisiae. These cases can be regarded as concept proofs indicating targeted engineering might help to create high-efficiency cell factories based upon constructed biological components

Abnormal inter-ventricular diastolic mechanical delay in patients with ST-segment elevation myocardial infarction

Abstract Background This study aimed to investigate the ventricular mechanical relaxation pattern and its clinical influence in patients with ST-segment elevation myocardial infarction (STEMI). Methods Echocardiography was performed to measure mitral and tricuspid diastolic opening times. Left ventricular diastolic mechanical delay (LVMDd) was defined as diastolic filling of the right ventricle earlier than that of the left ventricle, and right ventricular diastolic mechanical delay (RVMDd) was defined as the right ventricular diastolic filling later than left ventricular filling. Results Among 152 patients with STEMI, 100 (65.8%) had LVMDd, and 47 (30.9%) had RVMDd. In-hospital complications were significantly increased in patients with RVMDd (61.6% vs. 41.0%, P = 0.017). Those with RVMDd exhibited significantly lower left ventricular global longitudinal strain (11.7 ± 4.1% vs. 13.2 ± 4.0%, P = 0.035), global work index (913.8 ± 365.9 vs. 1098.9 ± 358.8 mmHg%, P = 0.005) and global constructive work (1218.6 ± 392.8 vs. 1393.7 ± 432.7 mmHg%, P = 0.021). Mitral deceleration time significantly decreased (127.4 ± 33.5 vs. 145.6 ± 41.7 ms, P = 0.012), and the ratio of early mitral inflow to early mitral annular velocity (E/E’) significantly increased [13.0(11.0–20.0) vs. 11.9(9.3–14.3), P = 0.006] in the RVMDd group. Logistic regression analysis showed that age (odds ratio [OR]:0.920; P = 0.001), brain natriuretic peptide level (OR: 1.1002; P = 0.036) and mitral E/E’ (OR: 1.187; P = 0.003) were independently associated with RVMDd. Conclusions Delayed right ventricular filling is related to more severe left ventricular systolic and diastolic dysfunction in STEMI patients. More attention should be paid to patients with RVMDd to prevent adverse events during hospitalization

National-Scale Geochemical Baseline and Anomalies of Chromium in Papua New Guinea

Papua New Guinea (PNG) is located at the convergence edge of the Pacific Plate and the Indo-Australian Plate, consisting of three units. There are three chromium mineralization types in PNG. Based on national-scale geochemical mapping in PNG during 2015–2018, 1399 samples of stream sediments were collected from Highland Region, Papua Peninsula, and New Guinea Islands. This paper preliminarily studied chromium’s geochemical background, spatial distribution characteristics, and geochemical anomalies. The chromium concentration ranged from 3 ppm to 74,600 ppm, with a median value of 145 ppm, which was higher than the upper crustal abundance of chromium and the chromium geochemical baseline of Europe, Australia, North America, and China. In terms of stream sediment samples in different tectonic units, as mafic–ultramafic magmatic rocks are widely developed, the median chromium values of the New Guinea Orogen, including the Papuan Fold Belt, the New Guinea Thrust Belt, the Finisterre Terrane, the Aure Fold Belt, the Eastern Fold Belt, and the Eastern Papuan Composite Terrane, were higher than the value of the Melanesian Arc. The ophiolitic complexes, such as the April ophiolite, the Marum ophiolite, and the Papua ultramafic belt, significantly correlated with the higher chromium concentration. Eleven chromium high anomalies with mineralization potential were delineated, including three laterite and podiform prospecting areas and eight placer prospecting areas. Based on the chromium–nickel integrated anomaly map, comprehensive exploration and exploitation of nickel and chromium can be carried out in 1 and 11 high anomaly areas related to lateritic mineralization