Identifying novel phenotypes of elevated left ventricular end diastolic pressure using hierarchical clustering of features derived from electromechanical waveform data

Introduction Elevated left ventricular end diastolic pressure (LVEDP) is a consequence of compromised left ventricular compliance and an important measure of myocardial dysfunction. An algorithm was developed to predict elevated LVEDP utilizing electro-mechanical (EM) waveform features. We examined the hierarchical clustering of selected features developed from these EM waveforms in order to identify important patient subgroups and assess their possible prognostic significance. Materials and methods Patients presenting with cardiovascular symptoms (N = 396) underwent EM data collection and direct LVEDP measurement by left heart catheterization. LVEDP was classified as non-elevated ( ≤ 12 mmHg) or elevated (≥25 mmHg). The 30 most contributive features to the algorithm output were extracted from EM data and input to an unsupervised hierarchical clustering algorithm. The resultant dendrogram was divided into five clusters, and patient metadata overlaid. Results The cluster with highest LVEDP (cluster 1) was most dissimilar from the lowest LVEDP cluster (cluster 5) in both clustering and with respect to clinical characteristics. In contrast to the cluster demonstrating the highest percentage of elevated LVEDP patients, the lowest was predominantly non-elevated LVEDP, younger, lower BMI, and males with a higher rate of significant coronary artery disease (CAD). The next adjacent cluster (cluster 2) to that of the highest LVEDP (cluster 1) had the second lowest LVEDP of all clusters. Cluster 2 differed from Cluster 1 primarily based on features extracted from the electrical data, and those that quantified predictability and variability of the signal. There was a low predictability and high variability in the highest LVEDP cluster 1, and the opposite in adjacent cluster 2. Conclusion This analysis identified subgroups of patients with varying degrees of LVEDP elevation based on waveform features. An approach to stratify movement between clusters and possible progression of myocardial dysfunction may include changes in features that differentiate clusters; specifically, reductions in electrical signal predictability and increases in variability. Identification of phenotypes of myocardial dysfunction evidenced by elevated LVEDP and knowledge of factors promoting transition to clusters with higher levels of left ventricular filling pressures could permit early risk stratification and improve patient selection for novel therapeutic interventions

Farmers’ attitudes about farming and the environment: A survey of conventional and organic farmers

Farmers have been characterized as people whose ties to the land have given them a deep awareness of natural cycles, appreciation for natural beauty and sense of responsibility as stewards. At the same time, their relationship to the land has been characterized as more utilitarian than that of others who are less directly dependent on its bounty. This paper explores this tension by comparing the attitudes and beliefs of a group of conventional farmers to those of a group of organic farmers. It was found that while both groups reject the idea that a farmer’s role is to conquer nature, organic farmers were significantly more supportive of the notion that humans should live in harmony with nature. Organic farmers also reported a greater awareness of and appreciation for nature in their relationship with the land. Both groups view independence as a main benefit of farming and a lack of financial reward as its main drawback. Overall, conventional farmers report more stress in their lives although they also view themselves in a caretaker role for the land more than do the organic farmers. In contrast, organic farmers report more satisfaction with their lives, a greater concern for living ethically, and a stronger perception of community. Finally, both groups are willing to have their rights limited (organic farmers somewhat more so) but they do not trust the government to do so.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83671/1/Sullivan,_S.,_E._McCann,_R._De_Young_&_D._Erickson_(1996)._Farmers_attitudes_about_farming_and_the_environment,_JAEE,_9,_123-143.pd

Cardiac Phase Space Tomography: A novel method of assessing coronary artery disease utilizing machine learning

BACKGROUND: Artificial intelligence (AI) techniques are increasingly applied to cardiovascular (CV) medicine in arenas ranging from genomics to cardiac imaging analysis. Cardiac Phase Space Tomography Analysis (cPSTA), employing machine-learned linear models from an elastic net method optimized by a genetic algorithm, analyzes thoracic phase signals to identify unique mathematical and tomographic features associated with the presence of flow-limiting coronary artery disease (CAD). This novel approach does not require radiation, contrast media, exercise, or pharmacological stress. The objective of this trial was to determine the diagnostic performance of cPSTA in assessing CAD in patients presenting with chest pain who had been referred by their physician for coronary angiography. METHODS: This prospective, multicenter, non-significant risk study was designed to: 1) develop machine-learned algorithms to assess the presence of CAD (defined as one or more ≥ 70% stenosis, or fractional flow reserve ≤ 0.80) and 2) test the accuracy of these algorithms prospectively in a naïve verification cohort. This report is an analysis of phase signals acquired from 606 subjects at rest just prior to angiography. From the collective phase signal data, features were extracted and paired with the known angiographic results. A development set, consisting of signals from 512 subjects, was used for machine learning to determine an algorithm that correlated with significant CAD. Verification testing of the algorithm was performed utilizing previously untested phase signals from 94 subjects. RESULTS: The machine-learned algorithm had a sensitivity of 92% (95% CI: 74%-100%) and specificity of 62% (95% CI: 51%-74%) on blind testing in the verification cohort. The negative predictive value (NPV) was 96% (95% CI: 85%-100%). CONCLUSIONS: These initial multicenter results suggest that resting cPSTA may have comparable diagnostic utility to functional tests currently used to assess CAD without requiring cardiac stress (exercise or pharmacological) or exposure of the patient to radioactivity

Data_Sheet_1_Identifying novel phenotypes of elevated left ventricular end diastolic pressure using hierarchical clustering of features derived from electromechanical waveform data.CSV

IntroductionElevated left ventricular end diastolic pressure (LVEDP) is a consequence of compromised left ventricular compliance and an important measure of myocardial dysfunction. An algorithm was developed to predict elevated LVEDP utilizing electro-mechanical (EM) waveform features. We examined the hierarchical clustering of selected features developed from these EM waveforms in order to identify important patient subgroups and assess their possible prognostic significance.Materials and methodsPatients presenting with cardiovascular symptoms (N = 396) underwent EM data collection and direct LVEDP measurement by left heart catheterization. LVEDP was classified as non-elevated ( ≤ 12 mmHg) or elevated (≥25 mmHg). The 30 most contributive features to the algorithm output were extracted from EM data and input to an unsupervised hierarchical clustering algorithm. The resultant dendrogram was divided into five clusters, and patient metadata overlaid.ResultsThe cluster with highest LVEDP (cluster 1) was most dissimilar from the lowest LVEDP cluster (cluster 5) in both clustering and with respect to clinical characteristics. In contrast to the cluster demonstrating the highest percentage of elevated LVEDP patients, the lowest was predominantly non-elevated LVEDP, younger, lower BMI, and males with a higher rate of significant coronary artery disease (CAD). The next adjacent cluster (cluster 2) to that of the highest LVEDP (cluster 1) had the second lowest LVEDP of all clusters. Cluster 2 differed from Cluster 1 primarily based on features extracted from the electrical data, and those that quantified predictability and variability of the signal. There was a low predictability and high variability in the highest LVEDP cluster 1, and the opposite in adjacent cluster 2.ConclusionThis analysis identified subgroups of patients with varying degrees of LVEDP elevation based on waveform features. An approach to stratify movement between clusters and possible progression of myocardial dysfunction may include changes in features that differentiate clusters; specifically, reductions in electrical signal predictability and increases in variability. Identification of phenotypes of myocardial dysfunction evidenced by elevated LVEDP and knowledge of factors promoting transition to clusters with higher levels of left ventricular filling pressures could permit early risk stratification and improve patient selection for novel therapeutic interventions.</p

Table_1_Identifying novel phenotypes of elevated left ventricular end diastolic pressure using hierarchical clustering of features derived from electromechanical waveform data.DOCX

IntroductionElevated left ventricular end diastolic pressure (LVEDP) is a consequence of compromised left ventricular compliance and an important measure of myocardial dysfunction. An algorithm was developed to predict elevated LVEDP utilizing electro-mechanical (EM) waveform features. We examined the hierarchical clustering of selected features developed from these EM waveforms in order to identify important patient subgroups and assess their possible prognostic significance.Materials and methodsPatients presenting with cardiovascular symptoms (N = 396) underwent EM data collection and direct LVEDP measurement by left heart catheterization. LVEDP was classified as non-elevated ( ≤ 12 mmHg) or elevated (≥25 mmHg). The 30 most contributive features to the algorithm output were extracted from EM data and input to an unsupervised hierarchical clustering algorithm. The resultant dendrogram was divided into five clusters, and patient metadata overlaid.ResultsThe cluster with highest LVEDP (cluster 1) was most dissimilar from the lowest LVEDP cluster (cluster 5) in both clustering and with respect to clinical characteristics. In contrast to the cluster demonstrating the highest percentage of elevated LVEDP patients, the lowest was predominantly non-elevated LVEDP, younger, lower BMI, and males with a higher rate of significant coronary artery disease (CAD). The next adjacent cluster (cluster 2) to that of the highest LVEDP (cluster 1) had the second lowest LVEDP of all clusters. Cluster 2 differed from Cluster 1 primarily based on features extracted from the electrical data, and those that quantified predictability and variability of the signal. There was a low predictability and high variability in the highest LVEDP cluster 1, and the opposite in adjacent cluster 2.ConclusionThis analysis identified subgroups of patients with varying degrees of LVEDP elevation based on waveform features. An approach to stratify movement between clusters and possible progression of myocardial dysfunction may include changes in features that differentiate clusters; specifically, reductions in electrical signal predictability and increases in variability. Identification of phenotypes of myocardial dysfunction evidenced by elevated LVEDP and knowledge of factors promoting transition to clusters with higher levels of left ventricular filling pressures could permit early risk stratification and improve patient selection for novel therapeutic interventions.</p

Multicenter validation of a machine learning phase space electro-mechanical pulse wave analysis to predict elevated left ventricular end diastolic pressure at the point-of-care

BACKGROUND: Phase space is a mechanical systems approach and large-scale data representation of an object in 3-dimensional space. Whether such techniques can be applied to predict left ventricular pressures non-invasively and at the point-of-care is unknown. OBJECTIVE: This study prospectively validated a phase space machine-learned approach based on a novel electro-mechanical pulse wave method of data collection through orthogonal voltage gradient (OVG) and photoplethysmography (PPG) for the prediction of elevated left ventricular end diastolic pressure (LVEDP). METHODS: Consecutive outpatients across 15 US-based healthcare centers with symptoms suggestive of coronary artery disease were enrolled at the time of elective cardiac catheterization and underwent OVG and PPG data acquisition immediately prior to angiography with signals paired with LVEDP (IDENTIFY; NCT #03864081). The primary objective was to validate a ML algorithm for prediction of elevated LVEDP using a definition of ≥ 25 mmHg (study cohort) and normal LVEDP ≤ 12 mmHg (control cohort), using AUC as the measure of diagnostic accuracy. Secondary objectives included performance of the ML predictor in a propensity matched cohort (age and gender) and performance for an elevated LVEDP across a spectrum of comparative LVEDP (increments). Features were extracted from the OVG and PPG datasets and were analyzed using machine-learning approaches. RESULTS: The study cohort consisted of 684 subjects stratified into three LVEDP categories, ≤ 12 mmHg (N = 258), LVEDP 13-24 mmHg (N = 347), and LVEDP ≥ 25 mmHg (N = 79). Testing of the ML predictor demonstrated an AUC of 0.81 (95% CI 0.76-0.86) for the prediction of an elevated LVEDP with a sensitivity of 82% and specificity of 68%, respectively. Among a propensity matched cohort (N = 79) the ML predictor demonstrated a similar result AUC 0.79 (95% CI: 0.72-0.8). Using a constant definition of elevated LVEDP and varying the lower threshold across LVEDP the ML predictor demonstrated and AUC ranging from 0.79-0.82. CONCLUSION: The phase space ML analysis provides a robust prediction for an elevated LVEDP at the point-of-care. These data suggest a potential role for an OVG and PPG derived electro-mechanical pulse wave strategy to determine if LVEDP is elevated in patients with symptoms suggestive of cardiac disease

Utilization of the Cardiac Phase Space Tomography Analysis (cPSTA) System.

<p>Phase signal data are collected and transferred to cloud. The generated models and analysis are available for physician assessment. cPSTA System = Cardiac Phase Space Tomography Analysis System, CAD = coronary artery disease. Reprinted from presentation materials of A4L under a license, with permission from A4L and W20, original production 2016.</p

Demographics of population.

<p>Demographics of population.</p

Detecting flow-limiting CAD.

<p>Machine-Learned Predictor (cPSTA) Compared to Exercise SPECT [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198603#pone.0198603.ref007" target="_blank">7</a>] and Exercise ECG [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198603#pone.0198603.ref007" target="_blank">7</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198603#pone.0198603.ref026" target="_blank">26</a>].</p

Subgroup analyses of the performance of the machine-learned predictor.

Subgroup analyses of the performance of the machine-learned predictor.</p