Prediction of postoperative patient deterioration and unanticipated intensive care unit admission using perioperative factors.

BACKGROUND AND OBJECTIVES: Currently, no evidence-based criteria exist for decision making in the post anesthesia care unit (PACU). This could be valuable for the allocation of postoperative patients to the appropriate level of care and beneficial for patient outcomes such as unanticipated intensive care unit (ICU) admissions. The aim is to assess whether the inclusion of intra- and postoperative factors improves the prediction of postoperative patient deterioration and unanticipated ICU admissions. METHODS: A retrospective observational cohort study was performed between January 2013 and December 2017 in a tertiary Dutch hospital. All patients undergoing surgery in the study period were selected. Cardiothoracic surgeries, obstetric surgeries, catheterization lab procedures, electroconvulsive therapy, day care procedures, intravenous line interventions and patients under the age of 18 years were excluded. The primary outcome was unanticipated ICU admission. RESULTS: An unanticipated ICU admission complicated the recovery of 223 (0.9%) patients. These patients had higher hospital mortality rates (13.9% versus 0.2%, p<0.001). Multivariable analysis resulted in predictors of unanticipated ICU admissions consisting of age, body mass index, general anesthesia in combination with epidural anesthesia, preoperative score, diabetes, administration of vasopressors, erythrocytes, duration of surgery and post anesthesia care unit stay, and vital parameters such as heart rate and oxygen saturation. The receiver operating characteristic curve of this model resulted in an area under the curve of 0.86 (95% CI 0.83-0.88). CONCLUSIONS: The prediction of unanticipated ICU admissions from electronic medical record data improved when the intra- and early postoperative factors were combined with preoperative patient factors. This emphasizes the need for clinical decision support tools in post anesthesia care units with regard to postoperative patient allocation.

On the value of MRI for improved understanding of cuff-based oscillometric measurements.

Blood pressure (BP) is a key parameter in critical care and in cardiovascular disease management. BP is typically measured via cuff-based oscillometry. This method is highly inaccurate in hypo- and hypertensive patients. Improvements are difficult to achieve because oscillometry is not yet fully understood; many assumptions and uncertainties exist in models describing the process by which arterial pulsations become expressed within the cuff signal. As a result, it is also difficult to estimate other parameters via the cuff such as arterial stiffness, cardiac output and pulse wave velocity (PWV)-BP calibration. Many research modalities have been employed to study oscillometry (ultrasound, computer simulations, ex-vivo studies, measurement of PWV, mechanical analysis). However, uncertainties remain; additional investigation modalities are needed. In this study, we explore the extent to which MRI can help investigate oscillometric assumptions. Four healthy volunteers underwent a number of MRI scans of the upper arm during cuff inflation. It is found that MRI provides a novel perspective over oscillometry; the artery, surrounding tissue, veins and the cuff can be simultaneously observed along the entire length of the upper arm. Several existing assumptions are challenged: tissue compression is not isotropic, arterial transmural pressure is not uniform along the length of the cuff and propagation of arterial pulsations through tissue is likely impacted by patient-specific characteristics (vasculature position and tissue composition). Clinical Relevance- The cuff interaction with the vasculature is extremely complex; existing models are oversimplified. MRI is a valuable tool for further development of cuff-based physiological measurements.

Quality Improvement in the Preoperative Evaluation: Accuracy of an Automated Clinical Decision Support System to Calculate CHA2DS2-VASc Scores.

Background and Objectives: Clinical decision support systems are advocated to improve the quality and efficiency in healthcare. However, before implementation, validation of these systems needs to be performed. In this evaluation we tested our hypothesis that a computerized clinical decision support system can calculate the CHA2DS2-VASc score just as well compared to manual calculation, or even better and more efficiently than manual calculation in patients with atrial rhythm disturbances. Materials and Methods: In n = 224 patents, we calculated the total CHA2DS2-VASc score manually and by an automated clinical decision support system. We compared the automated clinical decision support system with manually calculation by physicians. Results: The interclass correlation between the automated clinical decision support system and manual calculation showed was 0.859 (0.611 and 0.931 95%-CI). Bland-Altman plot and linear regression analysis shows us a bias of -0.79 with limit of agreement (95%-CI) between 1.37 and -2.95 of the mean between our 2 measurements. The Cohen's kappa was 0.42. Retrospective analysis showed more human errors than algorithmic errors. Time it took to calculate the CHA2DS2-VASc score was 11 s per patient in the automated clinical decision support system compared to 48 s per patient with the physician. Conclusions: Our automated clinical decision support system is at least as good as manual calculation, may be more accurate and is more time efficient.

Validation of Heart Rate Extracted From Wrist-Based Photoplethysmography in the Perioperative Setting: Prospective Observational Study.

BACKGROUND: Measurement of heart rate (HR) through an unobtrusive, wrist-worn optical HR monitor (OHRM) could enable earlier recognition of patient deterioration in low acuity settings and enable timely intervention. OBJECTIVE: The goal of this study was to assess the agreement between the HR extracted from the OHRM and the gold standard 5-lead electrocardiogram (ECG) connected to a patient monitor during surgery and in the recovery period. METHODS: In patients undergoing surgery requiring anesthesia, the HR reported by the patient monitor's ECG module was recorded and stored simultaneously with the photopletysmography (PPG) from the OHRM attached to the patient's wrist. The agreement between the HR reported by the patient's monitor and the HR extracted from the OHRM's PPG signal was assessed using Bland-Altman analysis during the surgical and recovery phase. RESULTS: A total of 271.8 hours of data in 99 patients was recorded simultaneously by the OHRM and patient monitor. The median coverage was 86% (IQR 65%-95%) and did not differ significantly between surgery and recovery (Wilcoxon paired difference test P=.17). Agreement analysis showed the limits of agreement (LoA) of the difference between the OHRM and the ECG HR were within the range of 5 beats per minute (bpm). The mean bias was -0.14 bpm (LoA between -3.08 bpm and 2.79 bpm) and -0.19% (LoA between -5 bpm to 5 bpm) for the PPG- measured HR compared to the ECG-measured HR during surgery; during recovery, it was -0.11 bpm (LoA between -2.79 bpm and 2.59 bpm) and -0.15% (LoA between -3.92% and 3.64%). CONCLUSIONS: This study shows that an OHRM equipped with a PPG sensor can measure HR within the ECG reference standard of -5 bpm to 5 bpm or -10% to 10% in the perioperative setting when the PPG signal is of sufficient quality. This implies that an OHRM can be considered clinically acceptable for HR monitoring in low acuity hospitalized patients.

Modulation of Pulse Propagation and Blood Flow via Cuff Inflation-New Distal Insights.

In standard critical care practice, cuff sphygmomanometry is widely used for intermittent blood pressure (BP) measurements. However, cuff devices offer ample possibility of modulating blood flow and pulse propagation along the artery. We explore underutilized arrangements of sensors involving cuff devices which could be of use in critical care to reveal additional information on compensatory mechanisms. In our previous work, we analyzed the response of the vasculature to occlusion perturbations by means of observations obtained non-invasively. In this study, our aim is to (1) acquire additional insights by means of invasive measurements and (2) based on these insights, further develop cuff-based measurement strategies. Invasive BP experimental data is collected downstream from the cuff in two patients monitored in the OR. It is found that highly dynamic processes occur in the distal arm during cuff inflation. Mean arterial pressure increases in the distal artery by 20 mmHg, leading to a decrease in pulse transit time by 20 ms. Previous characterizations neglected such distal vasculature effects. A model is developed to reproduce the observed behaviors and to provide a possible explanation of the factors that influence the distal arm mechanisms. We apply the new findings to further develop measurement strategies aimed at acquiring information on pulse arrival time vs. BP calibration, artery compliance, peripheral resistance, artery-vein interaction.

The impact of the catheter to vein ratio on peripheral intravenous cannulation success, a post-hoc analyses.

BACKGROUND: Intravenous cannulation is usually the first procedure performed in modern healthcare, although establishing peripheral intravenous access is challenging in some patients. The impact of the ratio between venous diameter and the size of the inserted catheter (catheter to vein ratio, CVR) on the first attempt success rate can be of added value in clinical. This study tries to give insight into the consideration that must be made when selecting the target vein and the type of catheter, and proved the null hypothesis that an optimal CVR would not be associated with increased first attempt cannulation success. METHODS: This was a post-hoc analyses on adult patients admitted for peripheral intravenous cannulation. Intravenous cannulation was performed according to practice guidelines, by applying the traditional landmark approach. The CVR was calculated afterwards for each individual patient by dividing the external diameter of the inserted catheter by the diameter of the target vein, which was multiplied by 100%. RESULTS: In total, 610 patients were included. The median CVR was 0.39 (0.15) in patients with a successful first attempt, whereas patients with an unsuccessful first attempt had a median CVR of 0.55 (0.20) (P<0.001). The optimal cut-off point of the CVR was 0.41. First attempt cannulation was successful in 92% of patients with a CVR<0.41, whereas as those with a CVR>0.41 had a first attempt success rate of 65% (P<0.001). CONCLUSION: This first introduction of the CVR in relation to cannulation success should be further investigated. Although, measuring the venous diameter or detection of a vein with a specific diameter prior to cannulation may increase first attempt cannulation success.

Clinical Decision Support System-Assisted Pharmacy Intervention Reduces Feeding Tube-Related Medication Errors in Hospitalized Patients: A Focus on Medication Suitable for Feeding-Tube Administration.

BACKGROUND: Administering medication through an enteral feeding tube (FT) is a frequent cause of errors resulting in increased morbidity and cost. Studies on interventions to prevent these errors in hospitalized patients, however, are limited. OBJECTIVE: The objective was to study the effect of a clinical decision support system (CDSS)-assisted pharmacy intervention on the incidence of FT-related medication errors (FTRMEs) in hospitalized patients. METHODS: A pre-post intervention study was conducted between October 2014 and May 2015 in Catharina Hospital, the Netherlands. Patients who were admitted to the wards of bowel and liver disease, oncology, or neurology; using oral medication; and had an enteral FT were included. Preintervention patients were given care as usual. The intervention consisted of implementing a CDSS-assisted pharmacy check while also implementing standard operating procedures and educating personnel. An FTRME was defined as the administration of inappropriate medication through an enteral FT. The incidence was expressed as the number of FTRMEs per medication administration. Multivariate Poisson regression was used to calculate the incidence ratio (IR) comparing both phases. RESULTS: Eighty-one patients were included, 38 during preintervention and 43 during the intervention phase. Incidence of FTRMEs in the preintervention phase was 0.15 (95% CI, 0.07-0.23) vs 0.02 (95% CI, 0.00-0.04) in the intervention phase, resulting in an adjusted IR of 0.13 (95% CI, 0.10-0.18). DISCUSSION: Incidence of FTRMEs, as well as the IR, is comparable to previous studies. CONCLUSION: The intervention resulted in a substantial reduction in the incidence of FTRMEs.

The Modified A-DIVA Scale as a Predictive Tool for Prospective Identification of Adult Patients at Risk of a Difficult Intravenous Access: A Multicenter Validation Study.

Peripheral intravenous cannulation is the most common invasive hospital procedure but is associated with a high failure rate. This study aimed to improve the A-DIVA scale (Adult Difficult Intra Venous Access Scale) by external validation, to predict the likelihood of difficult intravenous access in adults. This multicenter study was carried out throughout five hospitals in the Netherlands. Adult participants were included, regardless of their indication for intravenous access, demographics, and medical history. The main outcome variable was defined as failed peripheral intravenous cannulation on the first attempt. A total of 3587 participants was included in this study. The first attempt success rate was 81%. Finally, five variables were included in the prediction model: a history of difficult intravenous cannulation, a difficult intravenous access as expected by the practitioner, the inability to detect a dilated vein by palpating and/or visualizing the extremity, and a diameter of the selected vein less than 3 millimeters. Based on a participant's individual score on the A-DIVA scale, they were classified into either a low, moderate, or high-risk group. A higher score on the A-DIVA scale indicates a higher risk of difficult intravenous access. The five-variable additive A-DIVA scale is a reliable and generalizable predictive scale to identify patients at risk of difficult intravenous access.

Barriers to ultrasound guidance for central venous access: a survey among Dutch intensivists and anaesthesiologists.

Accumulating evidence shows that ultrasound (US) guidance improves effectiveness and safety of central venous catheter (CVC) placement. Several international guidelines therefore recommend the use of US for placement of CVCs. However, surveys show that the landmark-based technique is still widely used, while the percentage of physicians using US is increasing less than expected. The goal of this study was to investigate current practice for central venous catheterization in anaesthesiology and intensive care in the Netherlands, identify barriers for further implementation of US guidance and to evaluate whether personality traits are associated with the choice of technique. We conducted a web-based national survey, distributed among members of the Dutch societies of anaesthesiology (NVA) and intensive care (NVIC). The survey contained questions regarding physician and hospital characteristics, frequency of US use and reasons for use or non-use, as well as the NEO-FFI-3, a validated, translated questionnaire to characterize personality traits according to the 'Big Five' concept. Response rate was 22% (506/2291), of which 400 had also the personality questionnaire complete. Ultrasound guidance was used always or almost always in 68%; barriers for US use were working in a non-academic non-teaching hospital, providing cardiac anaesthesia and more years of physician experience. Reasons for not using US were perceived lack of benefit, increased procedure time, lack of US equipment and fear of loss of landmark technique skills. 13% of respondents had never experienced a complication during CVC placement, and 67% knew of a complication occurring the past year at their department. Ultrasound was thought not to be able to prevent the complication in half of these cases. Of the personality traits, only neuroticism and extraversion showed a minor positive association with US guidance. A majority of anaesthesiologists and intensivists uses US guidance for CVC placement, but a significant proportion of physicians still prefers the landmark technique. Most arguments from respondents against US guidance can be challenged. Personality traits most likely do not play a major role in the acceptance of US guidance for central venous catheterization. A potential intervention to increase US use could be formalizing local hospital policies mandating compliance with US guidance. Future research can perhaps focus on cognitive biases that currently limit more widespread use of US guidance.

Robust and semantic needle detection in 3D ultrasound using orthogonal-plane convolutional neural networks.

PURPOSE: During needle interventions, successful automated detection of the needle immediately after insertion is necessary to allow the physician identify and correct any misalignment of the needle and the target at early stages, which reduces needle passes and improves health outcomes. METHODS: We present a novel approach to localize partially inserted needles in 3D ultrasound volume with high precision using convolutional neural networks. We propose two methods based on patch classification and semantic segmentation of the needle from orthogonal 2D cross-sections extracted from the volume. For patch classification, each voxel is classified from locally extracted raw data of three orthogonal planes centered on it. We propose a bootstrap resampling approach to enhance the training in our highly imbalanced data. For semantic segmentation, parts of a needle are detected in cross-sections perpendicular to the lateral and elevational axes. We propose to exploit the structural information in the data with a novel thick-slice processing approach for efficient modeling of the context. RESULTS: Our introduced methods successfully detect 17 and 22 G needles with a single trained network, showing a robust generalized approach. Extensive ex-vivo evaluations on datasets of chicken breast and porcine leg show 80 and 84% F1-scores, respectively. Furthermore, very short needles are detected with tip localization errors of less than 0.7 mm for lengths of only 5 and 10 mm at 0.2 and 0.36 mm voxel sizes, respectively. CONCLUSION: Our method is able to accurately detect even very short needles, ensuring that the needle and its tip are maximally visible in the visualized plane during the entire intervention, thereby eliminating the need for advanced bi-manual coordination of the needle and transducer.

Pressure gradient vs. flow relationships to characterize the physiology of a severely stenotic aortic valve before and after transcatheter valve implantation.

Aims: Echocardiography and tomographic imaging have documented dynamic changes in aortic stenosis (AS) geometry and severity during both the cardiac cycle and stress-induced increases in cardiac output. However, corresponding pressure gradient vs. flow relationships have not been described. Methods and results: We recruited 16 routine transcatheter aortic valve implantations (TAVI's) for graded dobutamine infusions both before and after implantation; 0.014″ pressure wires in the aorta and left ventricle (LV) continuously measured the transvalvular pressure gradient (ΔP) while a pulmonary artery catheter regularly assessed cardiac output by thermodilution. Before TAVI, ΔP did not display a consistent relationship with transvalvular flow (Q). Neither linear resistor (median R2 0.16) nor quadratic orifice (median R2 < 0.01) models at rest predicted stress observations; the severely stenotic valve behaved like a combination. The unitless ratio of aortic to left ventricular pressures during systolic ejection under stress conditions correlated best with post-TAVI flow improvement. After TAVI, a highly linear relationship (median R2 0.96) indicated a valid valve resistance. Conclusion: Pressure loss vs. flow curves offer a fundamental fluid dynamic synthesis for describing aortic valve pathophysiology. Severe AS does not consistently behave like an orifice (as suggested by Gorlin) or a resistor, whereas TAVI devices behave like a pure resistor. During peak dobutamine, the ratio of aortic to left ventricular pressures during systolic ejection provides a 'fractional flow reserve' of the aortic valve that closely approximates the complex, changing fluid dynamics. Because resting assessment cannot reliably predict stress haemodynamics, 'valvular fractional flow' warrants study to explain exertional symptoms in patients with only moderate AS at rest.

Aligning Event Logs to Task-Time Matrix Clinical Pathways in BPMN for Variance Analysis.

Clinical pathways (CPs) are popular healthcare management tools to standardize care and ensure quality. Analyzing CP compliance levels and variances is known to be useful for training and CP redesign purposes. Flexible semantics of the business process model and notation (BPMN) language has been shown to be useful for the modeling and analysis of complex protocols. However, in practical cases one may want to exploit that CPs often have the form of task-time matrices. This paper presents a new method parsing complex BPMN models and aligning traces to the models heuristically. A case study on variance analysis is undertaken, where a CP from the practice and two large sets of patients data from an electronic medical record (EMR) database are used. The results demonstrate that automated variance analysis between BPMN task-time models and real-life EMR data are feasible, whereas that was not the case for the existing analysis techniques. We also provide meaningful insights for further improvement.

Noninvasive pulmonary transit time: A new parameter for general cardiac performance.

INTRODUCTION: Pulmonary transit time (PTT) assessed with contrast-enhanced ultrasound (CEUS) is a novel tool to evaluate cardiac function. PTT represents the time for a bolus of contrast to pass from the right to the left ventricle, measured according to the indicator dilution principles using CEUS. We investigated the hypothesis that PTT is a measure of general cardiac performance in patient populations eligible for cardiac resynchronization therapy (CRT). METHODS: The study population consisted of heart failure patients referred for CRT with NYHA class II-IV, left ventricular ejection fraction (LVEF)≤35% and QRS≥120 ms. CEUS, ECG, and blood were analyzed, and participants completed a quality of life questionnaire at baseline and 3 months after CRT implantation. Normalized PTT (nPTT) was calculated to compensate for the heart rate. Correlations were assessed with Pearson's or Spearman's coefficients and stratified for rhythm and NYHA class. RESULTS: The study population consisted of 94 patients (67 men) with a mean age of 70±8.9 years. (n)PTT was significantly correlated with left ventricular parameters (rs =-.487, P<.001), right ventricular parameters (r=-.282, P=.004), N-terminal pro-B-type natriuretic peptide (NT-proBNP) (rs =.475, P<.001), and quality of life (rs =.364, P<.001). Stronger significant correlations were found in patients in sinus rhythm. CONCLUSION: CEUS-derived PTT and nPTT correlate to a fair degree with measures of systolic and diastolic function, NT-pro-BNP, and quality of life. As CEUS-derived PTT can be obtained easily, noninvasively and at the bedside, it is a promising future measure of general cardiac performance.

Medical Instrument Detection in 3-Dimensional Ultrasound Data Volumes.

Ultrasound-guided medical interventions are broadly applied in diagnostics and therapy, e.g., regional anesthesia or ablation. A guided intervention using 2-D ultrasound is challenging due to the poor instrument visibility, limited field of view, and the multi-fold coordination of the medical instrument and ultrasound plane. Recent 3-D ultrasound transducers can improve the quality of the image-guided intervention if an automated detection of the needle is used. In this paper, we present a novel method for detecting medical instruments in 3-D ultrasound data that is solely based on image processing techniques and validated on various ex vivo and in vivo data sets. In the proposed procedure, the physician is placing the 3-D transducer at the desired position, and the image processing will automatically detect the best instrument view, so that the physician can entirely focus on the intervention. Our method is based on the classification of instrument voxels using volumetric structure directions and robust approximation of the primary tool axis. A novel normalization method is proposed for the shape and intensity consistency of instruments to improve the detection. Moreover, a novel 3-D Gabor wavelet transformation is introduced and optimally designed for revealing the instrument voxels in the volume, while remaining generic to several medical instruments and transducer types. Experiments on diverse data sets, including in vivo data from patients, show that for a given transducer and an instrument type, high detection accuracies are achieved with position errors smaller than the instrument diameter in the 0.5-1.5-mm range on average.

Comparison of cardiac magnetic resonance imaging and bio-impedance spectroscopy for the assessment of fluid displacement induced by external leg compression.

Heart failure is marked by frequent hospital admissions, often as a consequence of pulmonary congestion. Current gold standard techniques for thoracic fluid measurement require invasive heamodynamic access and therefore they are not suitable for continuous monitoring. Changes in thoracic impedance (TI) may enable non-invasive early detection of congestion and prevention of unplanned hospitalizations. However, the usefulness of TI to assess thoracic fluid status is limited by inter-subject variability and by the lack of reliable normalization methods. Indicator dilution methods allow absolute fluid volume estimation; cardiac magnetic resonance (CMR) has been recently proposed to apply indicator dilution methods in a minimally-invasive manner. In this study, we aim to compare bio-impedance spectroscopy (BIS) and CMR for the assessment of thoracic fluid status, and to determine their ability to detect fluid displacement induced by a leg compression procedure in healthy volunteers. A pressure gradient was applied across each subject's legs for 5 min (100-60 mmHg, distal to proximal). Each subject underwent a continuous TI-BIS measurement during the procedure, and repeated CMR-based indicator dilution measurements on a 1.5 T scanner at baseline, during compression, and after pressure release. The Cole-Cole and the local density random walk models were used for parameter extraction from TI-BIS and indicator dilution measurements, respectively. Intra-thoracic blood volume index (ITBI) derived from CMR, and extracellular fluid resistance (R E) from TI-BIS, were considered as thoracic fluid status measures. Eight healthy volunteers were included in this study. An increase in ITBI of 45.2 ± 47.2 ml m-2 was observed after the leg inflation (13.1 ± 15.1% w.r.t. baseline, p < 0.05), while a decrease of -0.84 ± 0.39 Ω in R E (-1.7 ± 0.9% w.r.t. baseline, p < 0.05) was observed. ITBV and R E normalized by body mass index were strongly inversely correlated (r = -0.93, p < 0.05). In conclusion, an acute fluid displacement to the thoracic circulation was induced in healthy volunteers. Significant changes were observed in the considered thoracic fluid measures derived from BIS and CMR. Good correlation was observed between the two measurement techniques. Further clinical studies will be necessary to prospectively evaluate the value of a combination of the two techniques for prediction of re-hospitalizations after admission for heart failure.

Model-Based Characterization of the Transpulmonary Circulation by Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Heart Failure and Healthy Volunteers.

OBJECTIVES: Novel quantitative measures of transpulmonary circulation status may allow the improvement of heart failure (HF) patient management. In this work, we propose a method for the assessment of the transpulmonary circulation using measurements from indicator time intensity curves, derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) series. The derived indicator dilution parameters in healthy volunteers (HVs) and HF patients were compared, and repeatability was assessed. Furthermore, we compared the parameters derived using the proposed method with standard measures of cardiovascular function, such as left ventricular (LV) volumes and ejection fraction. MATERIALS AND METHODS: In total, 19 HVs and 33 HF patients underwent a DCE-MRI scan on a 1.5 T MRI scanner using a T1-weighted spoiled gradient echo sequence. Image loops with 1 heartbeat temporal resolution were acquired in 4-chamber view during ventricular late diastole, after the injection of a 0.1-mmol gadoteriol bolus. In a subset of subjects (8 HFs, 2 HVs), a second injection of a 0.3-mmol gadoteriol bolus was performed with the same imaging settings. The study was approved by the local institutional review board.Indicator dilution curves were derived, averaging the MR signal within regions of interest in the right and left ventricle; parametric deconvolution was performed between the right and LV indicator dilution curves to identify the impulse response of the transpulmonary dilution system. The local density random walk model was used to parametrize the impulse response; pulmonary transit time (PTT) was defined as the mean transit time of the indicator. λ, related to the Péclet number (ratio between convection and diffusion) for the dilution process, was also estimated. RESULTS: Pulmonary transit time was significantly prolonged in HF patients (8.70 ± 1.87 seconds vs 6.68 ± 1.89 seconds in HV, P < 0.005) and even stronger when normalized to subject heart rate (normalized PTT, 9.90 ± 2.16 vs 7.11 ± 2.17 in HV, dimensionless, P < 0.001). λ was significantly smaller in HF patients (8.59 ± 4.24 in HF vs 12.50 ± 17.09 in HV, dimensionless, P < 0.005), indicating a longer tail for the impulse response. Pulmonary transit time correlated well with established cardiovascular parameters (LV end-diastolic volume index, r = 0.61, P < 0.0001; LV ejection fraction, r = -0.64, P < 0.0001). The measurement of indicator dilution parameters was repeatable (correlation between estimates based on the 2 repetitions for PTT: r = 0.94, P < 0.001, difference between 2 repetitions 0.01 ± 0.60 second, for λ: r = 0.74, P < 0.01, difference 0.69 ± 4.39). CONCLUSIONS: Characterization of the transpulmonary circulation by DCE-MRI is feasible in HF patients and HVs. Significant differences are observed between indicator dilution parameters measured in HVs and HF patients; preliminary results suggest good repeatability for the proposed parameters.

Pulmonary transit time measurement by contrast-enhanced ultrasound in left ventricular dyssynchrony.

BACKGROUND: Pulmonary transit time (PTT) is an indirect measure of preload and left ventricular function, which can be estimated using the indicator dilution theory by contrast-enhanced ultrasound (CEUS). In this study, we first assessed the accuracy of PTT-CEUS by comparing it with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Secondly, we tested the hypothesis that PTT-CEUS correlates with the severity of heart failure, assessed by MRI and N-terminal pro-B-type natriuretic peptide (NT-proBNP). METHODS AND RESULTS: Twenty patients referred to our hospital for cardiac resynchronization therapy (CRT) were enrolled. DCE-MRI, CEUS, and NT-proBNP measurements were performed within an hour. Mean transit time (MTT) was obtained by estimating the time evolution of indicator concentration within regions of interest drawn in the right and left ventricles in video loops of DCE-MRI and CEUS. PTT was estimated as the difference of the left and right ventricular MTT. Normalized PTT (nPTT) was obtained by multiplication of PTT with the heart rate. Mean PTT-CEUS was 10.5±2.4s and PTT-DCE-MRI was 10.4±2.0s (P=0.88). The correlations of PTT and nPTT by CEUS and DCE-MRI were strong; r=0.75 (P=0.0001) and r=0.76 (P=0.0001), respectively. Bland-Altman analysis revealed a bias of 0.1s for PTT. nPTT-CEUS correlated moderately with left ventricle volumes. The correlations for PTT-CEUS and nPTT-CEUS were moderate to strong with NT-proBNP; r=0.54 (P=0.022) and r=0.68 (P=0.002), respectively. CONCLUSIONS: (n)PTT-CEUS showed strong agreement with that by DCE-MRI. Given the good correlation with NT-proBNP level, (n)PTT-CEUS may provide a novel, clinically feasible measure to quantify the severity of heart failure. CLINICAL TRIAL REGISTRY: NCT01735838.

Reliability, repeatability, and reproducibility of pulmonary transit time assessment by contrast enhanced echocardiography.

BACKGROUND: The aim of this study is to investigate the inter and intra-rater reliability, repeatability, and reproducibility of pulmonary transit time (PTT) measurement in patients using contrast enhanced ultrasound (CEUS), as an indirect measure of preload and left ventricular function. METHODS: Mean transit times (MTT) were measured by drawing a region of interest (ROI) in right and left cardiac ventricle in the CEUS loops. Acoustic intensity dilution curves were obtained from the ROIs. MTTs were calculated by applying model-based fitting on the dilution curves. PTT was calculated as the difference of the MTTs. Eight raters with different levels of experience measured the PTT (time moment 1) and repeated the measurement within a week (time moment 2). Reliability and agreement were assessed using intra-class correlations (ICC) and Bland-Altman analysis. Repeatability was tested by estimating the variance of means (ANOVA) of three injections in each patient at different doses. Reproducibility was tested by the ICC of the two time moments. RESULTS: Fifteen patients with heart failure were included. The mean PTT was 11.8 ± 3.1 s at time moment 1 and 11.7 ± 2.9 s at time moment 2. The inter-rater reliability for PTT was excellent (ICC = 0.94). The intra-rater reliability per rater was between 0.81-0.99. Bland-Altman analysis revealed a bias of 0.10 s within the rater groups. Reproducibility for PTT showed an ICC = 0.94 between the two time moments. ANOVA showed no significant difference between the means of the three different doses F = 0.048 (P = 0.95). The mean and standard deviation for PTT estimates at three different doses was 11.6 ± 3.3 s. CONCLUSIONS: PTT estimation using CEUS shows a high inter- and intra-rater reliability, repeatability at three different doses, and reproducibility by ROI drawing. This makes the minimally invasive PTT measurement using contrast echocardiography ready for clinical evaluation in patients with heart failure and for preload estimation.