Although transthoracic three-dimensional echocardiography (3DE) is now recommended by guidelines for left ventricular (LV) volumetric measurements, widespread implementation has been limited due to time constraints and required expertise. We hypothesized that fully automated 3DE left chamber quantification software might provide accurate measurements, and that its application could eliminate these obstacles.
To address this hypothesis, we conducted a systematic review and meta-analysis following a search for studies that compared LV volumes and ejection fraction (EF) using fully automated 3DE software (HeartModel or Dynamic HeartModel, Philips Healthcare, Andover, MA, USA) with cardiac magnetic resonance (CMR), from 2015 to 2021. A random effects model was used to determine biases, correlations, and 95 % confidence intervals (CI) of LV end-diastolic volume (EDV), end-systolic volume (ESV), and EF. Subgroup and meta-regression analyses were performed to determine effects of moderators on the outcome.
Of 12 studies (616 subjects), mean differences and 95 % CIs in EDV, ESV, and EF between fully automated 3DE software and CMR were -19.6 mL (95 % CI; -27.6 to -11.5 mL), -11.4 mL (-16.7 to -6.2 mL), and 0.4 % (-1.1 to 2.0 %), respectively. Corresponding correlation values between the two methods were 0.91 (0.86-0.94), 0.89 (0.82-0.93), and 0.85 (0.81-0.88), respectively. Meta-regression analysis revealed that there were no effects of either publication year, type of software, or type of analysis on the outcome of LV volumetric and functional parameters except for publication year on LVESV correlation values.
Although 3DE still underestimates LV volumes, the observed differences were no >20 mL. EF showed similar values to CMR. Excellent correlations between the two techniques make fully automated 3DE left chamber quantification software useful for routine clinical practice in adult population.

Left ventricular ejection fraction (LVEF) and end-systolic volume (ESV) remain the main imaging biomarkers for post-acute myocardial infarction (AMI) risk stratification. However, they are limited to global systolic function and fail to capture functional and anatomical regional abnormalities, hindering their performance in risk stratification.
This study aimed to identify novel 3-dimensional (3D) imaging end-systolic (ES) shape and contraction descriptors toward risk-related features and superior prognosis in AMI.
A multicenter cohort of AMI survivors (n = 1,021; median age 63 years; 74.5% male) who underwent cardiac magnetic resonance (CMR) at a median of 3 days after infarction were considered for this study. The clinical endpoint was the 12-month rate of major adverse cardiac events (MACE; n = 73), consisting of all-cause death, reinfarction, and new congestive heart failure. A fully automated pipeline was developed to segment CMR images, build 3D statistical models of shape and contraction in AMI, and find the 3D patterns related to MACE occurrence.
The novel ES shape markers proved to be superior to ESV (median cross-validated area under the receiver-operating characteristic curve 0.681 [IQR: 0.679-0.684] vs 0.600 [IQR: 0.598-0.602]; P < 0.001); and 3D contraction to LVEF (0.716 [IQR: 0.714-0.718] vs 0.681 [IQR: 0.679-0.684]; P < 0.001) in MACE occurrence prediction. They also contributed to a significant improvement in a multivariable setting including CMR markers, cardiovascular risk factors, and basic patient characteristics (0.747 [IQR: 0.745-0.749]; P < 0.001). Based on these novel 3D descriptors, 3 impairments caused by AMI were identified: global, anterior, and basal, the latter being the most complementary signature to already known predictors.
The quantification of 3D differences in ES shape and contraction, enabled by a fully automated pipeline, improves post-AMI risk prediction and identifies shape and contraction patterns related to MACE occurrence.

The quantitative analysis of substances in dried blood spots (DBS) has gained vast popularity in the past decade. The World Anti-Doping Agency (WADA) also recently committed to implementing DBS. Currently, DBS sampling mainly has focused on various volumetric sampling devices such as Hemaxis, Capitainer, and Mitra. These devices are designed to collect a specific sample volume, independent of the hematocrit (HCT), to enable quantitative DBS analysis. Here, we present an automated solution that makes the necessity of volumetric sampling for quantitative DBS analysis obsolete. Combining automated reflectance-based HCT correction in combination with fully automated DBS LC-MS/MS analysis, the novel strategy permits high-throughput analysis in combination with HCT independence. Studying the model compound phosphatidylethanol 16:0/18:1, which is HCT-dependent due to incorporation into red blood cells, an implementation of DBS HCT normalization is presented. First, the performance of the automated HCT module with DBS is demonstrated compared to standardized HCT analysis from whole blood using a centrifuge. Second, the HCT dependency of fully automated PEth analysis from DBS is evaluated. Third, a solution to correct for the HCT dependency of PEth using the HCT scanner is presented. The study demonstrates that as soon as the HCT dependence of an analyte is known, a correction factor can be applied for the normalization of HCT levels. In the context of PEth, a linear increase in PEth concentration was observed, as the analyte is primarily located within the cellular fraction. Based on the obtained results, the use of a common correction factor for PEth DBS is possible.

The impact of the hematocrit (HCT) on the dried blood spot\'s (DBS) spreading area is one of the most important hurdles which prevents the full acceptance of quantitative microsampling strategies. Several destructive- and non-destructive strategies to assess the HCT from a DBS post-sampling have been presented. Unfortunately, the current methods are either labor-intensive, require a complicated algorithm, or are not automatable. Here, we present a novel setup that permits the fully automated reflectance analysis to measure the HCT from a DBS. The underlying principle is based on the concept presented by Capiau et al. for the non-destructive single-wavelength measurement of the HCT. The novel module was embedded within the DBS-MS 500 platform to enable high-throughput analysis of hematocrit values in combination with automated DBS extraction. The novel setup was assessed and optimized for the probe to card distance, stability, anti-coagulant, spotting volume, scan number, calibration variability, accuracy, and precision. It showed excellent inter-day (≤3.7%) and intra-day (≤1.16%) precision, as well as high accuracy when analyzing authentic samples 101%±7% (range:87%-127%). Besides, the simple and straightforward application of an HCT correction for DBS was demonstrated during a pharmacokinetic study with diclofenac involving three subjects. Thereby, the sample\'s HCT and the HCT impact on the analyte was assessed and compensated. In conclusion, the novel setup enables quantitative analysis of non-volumetric samples in an automated fashion without compromising the concept of cost-effective, minimally invasive sampling.

The World Anti-Doping Agency (WADA) and the International Testing Agency (ITA) recently announced the development and implementation of dried blood spot (DBS) testing for routine analysis in time for the 2022 Winter Olympic and Paralympic Games in Beijing. Following the introduction of a ban on the use of tramadol in competition in March 2019, the Union Cycliste International (UCI) started a pilot study for the manual analysis of tramadol in DBS for antidoping purposes. In this context, we present a fully automated LC-MS/MS-based method with automated sample preparation using a CAMAG DBS-MS 500 for the analysis of tramadol and its metabolite O-desmethyltramadol in DBS. The presented approach reduces manual handling in the laboratory to an absolute minimum, only requiring the preparation of calibration and quality control DBS cards. The method was developed, optimized, and validated before performing cross-validation with a liquid blood-based analysis method using authentic samples from forensic cases. During the validation process, the method showed an extraction efficiency of 62%, linearity r2 > 0.99, accuracy and precision (within ± 15% and ± 20% at the LLOQ) for the determination of tramadol and O-desmethyltramadol. Method comparison in liquid blood with 26 samples showed good agreement (90 ± 19% for tramadol and 94 ± 14% for O-desmethyltramadol). In conclusion, automated analysis of tramadol and O-desmethyltramadol in DBS provides a fast and accurate solution for antidoping screening. It is suited for high-throughput analysis, having a run time of about 4 min per sample. Furthermore, with the automated approach, manual sample extraction becomes obsolete.

BACKGROUND: Study on automated three-dimensional (3D) quantification of left heart parameters by using Heartmodel software is still in the early stage and fully automatic analysis was not clearly achieved. The aim of our study was to evaluate the performance of this new technology in measuring left ventricular (LV) volume and ejection fraction (EF) in patients with a variety of heart diseases on the basis of rationally determining the default endocardial border values.
METHODS: Subjects with a variety of heart diseases were included prospectively. High quality Heartmodel images were selected to determine the end-diastolic and end-systolic default values of endocardial border. The accuracy and reproducibility of automated three-dimensional echocardiography (3DE) for measuring LV end-diastolic volume (EDV), end-systolic volume (ESV) and EF were evaluated with the traditional manual 3DE as the relative standard.
RESULTS: Ninety seven subjects were enrolled in the study. The default endocardial border values were determined as 66% and 40% for end-diastole (ED) and end-systole (ES), respectively. Most of the subjects (84/97) were automatically analyzed by Heartmodel software without manual adjustment, revealing a close correlation of automated 3DE with manual 3DE in measuring EDV, ESV and EF (r-values: EDV: 0.96, ESV: 0.97, EF: 0.96). The EDV and ESV values obtained by automated 3DE were higher than those measured by manual 3DE (biases: EDV: 16 ± 18 ml, ESV: 11 ± 12 ml). The intra- and inter-observer reproducibility of automated 3DE was better than that of manual 3DE. Automated 3DE with manual adjustment showed good consistency with manual 3DE in assessing the impairment degree of systolic function in patients with wall motion abnormalities (n = 58), (Kappa = 0.74, P = 0.00).
CONCLUSIONS: Fully automated 3DE quantification of LV volume and EF could be achieved in most patients. Since automated 3DE was accurate and more reproducible, it could replace the existing manual 3DE technology and be routinely used in clinical practice.