Adverse Cardiovascular Effects of Nicotine Delivered by Chronic Electronic Cigarettes or Standard Cigarettes Captured by Cardiovascular Intrinsic Frequencies.

BACKGROUND: Electronic cigarettes have gained popularity as a nicotine delivery system, which has been recommended by some as an aid to help people quit traditional smoking. The potential long-term effects of vaping on the cardiovascular system, as well as how their effects compare with those from standard cigarettes, are not well understood. The intrinsic frequency (IF) method is a systems approach for analysis of left ventricle and arterial function. Recent clinical studies have demonstrated the diagnostic and prognostic value of IF. Here, we aim to determine whether the novel IF metrics derived from carotid pressure waveforms can detect effects of nicotine (delivered by chronic exposure to electronic cigarette vapor or traditional cigarette smoke) on the cardiovascular system. METHODS AND RESULTS: One hundred seventeen healthy adult male and female rats were exposed to purified air (control), electronic cigarette vapor without nicotine, electronic cigarette vapor with nicotine, and traditional nicotine-rich cigarette smoke, after which hemodynamics were comprehensively evaluated. IF metrics were computed from invasive carotid pressure waveforms. Standard cigarettes significantly increased the first IF (indicating left ventricle contractile dysfunction). Electronic cigarettes with nicotine significantly reduced the second IF (indicating adverse effects on vascular function). No significant difference was seen in the IF metrics between controls and electronic cigarettes without nicotine. Exposure to electronic cigarettes with nicotine significantly increased the total IF variation (suggesting adverse effects on left ventricle-arterial coupling and its optimal state), when compared with electronic cigarettes without nicotine. CONCLUSIONS: Our IF results suggest that nicotine-containing electronic cigarettes adversely affect vascular function and left ventricle-arterial coupling, whereas standard cigarettes have an adverse effect on left ventricle function.

Detecting elevated left ventricular end diastolic pressure from simultaneously measured femoral pressure waveform and electrocardiogram.

Objective.Instantaneous, non-invasive evaluation of left ventricular end-diastolic pressure (LVEDP) would have significant value in the diagnosis and treatment of heart failure. A new approach called cardiac triangle mapping (CTM) has been recently proposed, which can provide a non-invasive estimate of LVEDP. We hypothesized that a hybrid machine-learning (ML) method based on CTM can instantaneously identify an elevated LVEDP using simultaneously measured femoral pressure waveform and electrocardiogram (ECG).Approach.We studied 46 patients (Age: 39-90 (66.4 ± 9.9), BMI: 20.2-36.8 (27.6 ± 4.1), 12 females) scheduled for clinical left heart catheterizations or coronary angiograms at University of Southern California Keck Medical Center. Exclusion criteria included severe mitral/aortic valve disease; severe carotid stenosis; aortic abnormalities; ventricular paced rhythm; left bundle branch and anterior fascicular blocks; interventricular conduction delay; and atrial fibrillation. Invasive LVEDP and pressure waveforms at the iliac bifurcation were measured using transducer-tipped Millar catheters with simultaneous ECG. LVEDP range was 9.3-40.5 mmHg. LVEDP = 18 mmHg was used as cutoff. Random forest (RF) classifiers were trained using data from 36 patients and blindly tested on 10 patients.Main results.Our proposed ML classifier models accurately predict true LVEDP classes using appropriate physics-based features, where the most accurate demonstrates 100.0% (elevated) and 80.0% (normal) success in predicting true LVEDP classes on blind data.Significance.We demonstrated that physics-based ML models can instantaneously classify LVEDP using information from femoral waveforms and ECGs. Although an invasive validation, the required ML inputs can be potentially obtained non-invasively.

Instantaneous detection of acute myocardial infarction and ischaemia from a single carotid pressure waveform in rats.

Aims: Myocardial infarction (MI) is one of the leading causes of death worldwide. It is well accepted that early diagnosis followed by early reperfusion therapy significantly increases the MI survival. Diagnosis of acute MI is traditionally based on the presence of chest pain and electrocardiogram (ECG) criteria. However, around 50% of the MIs are without chest pain, and ECG is neither completely specific nor definitive. Therefore, there is an unmet need for methods that allow detection of acute MI or ischaemia without using ECG. Our hypothesis is that a hybrid physics-based machine learning (ML) method can detect the occurrence of acute MI or ischaemia from a single carotid pressure waveform. Methods and results: We used a standard occlusion/reperfusion rat model. Physics-based ML classifiers were developed using intrinsic frequency parameters extracted from carotid pressure waveforms. ML models were trained, validated, and generalized using data from 32 rats. The final ML models were tested on an external stratified blind dataset from additional 13 rats. When tested on blind data, the best ML model showed specificity = 0.92 and sensitivity = 0.92 for detecting acute MI. The best model's specificity and sensitivity for ischaemia detection were 0.85 and 0.92, respectively. Conclusion: We demonstrated that a hybrid physics-based ML approach can detect the occurrence of acute MI and ischaemia from carotid pressure waveform in rats. Since carotid pressure waveforms can be measured non-invasively, this proof-of-concept pre-clinical study can potentially be expanded in future studies for non-invasive detection of MI or myocardial ischaemia.

A machine learning approach for computation of cardiovascular intrinsic frequencies.

Analysis of cardiovascular waveforms provides valuable clinical information about the state of health and disease. The intrinsic frequency (IF) method is a recently introduced framework that uses a single arterial pressure waveform to extract physiologically relevant information about the cardiovascular system. The clinical usefulness and physiological accuracy of the IF method have been well-established via several preclinical and clinical studies. However, the computational complexity of the current L2 optimization solver for IF calculations remains a bottleneck for practical deployment of the IF method in real-time settings. In this paper, we propose a machine learning (ML)-based methodology for determination of IF parameters from a single carotid waveform. We use a sequentially-reduced Feedforward Neural Network (FNN) model for mapping carotid waveforms to the output parameters of the IF method, thereby avoiding the non-convex L2 minimization problem arising from the conventional IF approach. Our methodology also includes procedures for data pre-processing, model training, and model evaluation. In our model development, we used both clinical and synthetic waveforms. Our clinical database is composed of carotid waveforms from two different sources: the Huntington Medical Research Institutes (HMRI) iPhone Heart Study and the Framingham Heart Study (FHS). In the HMRI and FHS clinical studies, various device platforms such as piezoelectric tonometry, optical tonometry (Vivio), and an iPhone camera were used to measure arterial waveforms. Our blind clinical test shows very strong correlations between IF parameters computed from the FNN-based method and those computed from the standard L2 optimization-based method (i.e., R≥0.93 and P-value ≤0.005 for each IF parameter). Our results also demonstrate that the performance of the FNN-based IF model introduced in this work is independent of measurement apparatus and of device sampling rate.

Assessment of Aortic Characteristic Impedance and Arterial Compliance from Non-invasive Carotid Pressure Waveform in The Framingham Heart Study.

The primary goal of this study was to test the hypothesis that a hybrid intrinsic frequency-machine learning (IF-ML) approach can accurately evaluate total arterial compliance (TAC) and aortic characteristic impedance (Zao) from a single noninvasive carotid pressure waveform in both women and men with heart failure (HF). TAC and Zao are cardiovascular biomarkers with established clinical significance. TAC is lower and Zao is higher in women than in men, so women are more susceptible to the consequent deleterious effects of them. Although the principles of TAC and Zao are pertinent to a multitude of cardiovascular diseases, including HF, their routine clinical use is limited because of the requirement for simultaneous measurements of flow and pressure waveforms. For this study, the data were obtained from the Framingham Heart Study (n = 6,201, 53% women). The reference values of Zao and TAC were computed from carotid pressure and aortic flow waveforms. IF parameters of carotid pressure waveform were used in ML models. IF models were developed on n = 5,168 of randomly selected data and blindly tested the remaining data (n = 1,033). The final models were evaluated in patients with HF. Correlations between IF-ML and reference values in all HF and HF with preserved ejection fraction for TAC were 0.88 and 0.90, and for Zao were 0.82 and 0.80, respectively. The classification accuracy in all HF and HF with preserved ejection fraction for TAC were 0.9 and 0.93, and for Zao were 0.81 and 0.89, respectively. In conclusion, the IF-ML method provides an accurate estimation of TAC and Zao in all subjects with HF and in the general population.

A coupled atrioventricular-aortic setup for in-vitro hemodynamic study of the systemic circulation: Design, fabrication, and physiological relevancy.

In-vitro models of the systemic circulation have gained a lot of interest for fundamental understanding of cardiovascular dynamics and for applied hemodynamic research. In this study, we introduce a physiologically accurate in-vitro hydraulic setup that models the hemodynamics of the coupled atrioventricular-aortic system. This unique experimental simulator has three major components: 1) an arterial system consisting of a human-scale artificial aorta along with the main branches, 2) an artificial left ventricle (LV) sac connected to a programmable piston-in-cylinder pump for simulating cardiac contraction and relaxation, and 3) an artificial left atrium (LA). The setup is designed in such a way that the basal LV is directly connected to the aortic root via an aortic valve, and to the LA via an artificial mitral valve. As a result, two-way hemodynamic couplings can be achieved for studying the effects that the LV, aorta, and LA have on each other. The collected pressure and flow measurements from this setup demonstrate a remarkable correspondence to clinical hemodynamics. We also investigate the physiological relevancies of isolated effects on cardiovascular hemodynamics of various major global parameters found in the circulatory system, including LV contractility, LV preload, heart rate, aortic compliance, and peripheral resistance. Subsequent control over such parameters ultimately captures physiological hemodynamic effects of LV systolic dysfunction, preload (cardiac) diseases, and afterload (arterial) diseases. The detailed design and fabrication of the proposed setup is also provided.

Effects of vessel wall mechanics on non-invasive evaluation of cardiovascular intrinsic frequencies.

Intrinsic Frequency (IF) is a systems-based approach that provides valuable information for hemodynamic monitoring of the left ventricle (LV), the arterial system, and their coupling. Recent clinical studies have demonstrated the clinical significance of this method for prognosis and diagnosis of cardiovascular diseases. In IF analysis, two dominant instantaneous frequencies (ω1 and ω2) are extracted from arterial pressure waveforms. The value of ω1 is related to the dynamics of the LV and the value of ω2 is related to the dynamics of vascular function. This work investigates the effects of vessel wall mechanics on the accuracy and applicability of IFs extracted from vessel wall displacement waveforms compared to IFs extracted from pressure waveforms. In this study, we used a computational approach employing a fluid-structure interaction finite element method for various wall mechanics governed by linearly elastic, hyperelastic, and viscoelastic models. Results show that for vessels with elastic wall behavior, the error between displacement-based and pressure-based IFs is negligible. In the presence of stenosis or aneurysm in elastic arteries, the maximum errors associated with displacement-based IFs is less than 2%. For non-linear elastic and viscoelastic arteries, errors are more pronounced (where the former reaches up to 11% and the latter up to 27%). Our results ultimately suggest that displacement-based computations of ω1 and ω2 are accurate in vessels that exhibit elastic behavior (such as carotid arteries) and are suitable surrogates for pressure-based IFs. This is clinically significant because displacement-based IFs can be measured non-invasively.

Scalability of cardiovascular intrinsic frequencies: Validations in preclinical models and non-invasive clinical studies.

AIMS: Cardiovascular intrinsic frequencies (IFs) are associated with cardiovascular health and disease, separately capturing the systolic and diastolic information contained in a single (uncalibrated) arterial waveform. Previous clinical investigations related to IF have been restricted to studying chronic conditions, and hence its applicability for acute cardiovascular diseases has not been explored. Studies of cardiovascular complications such as acute myocardial infarction are difficult to perform in humans due to the high-risk and invasive nature of such procedures. Although they can be performed in preclinical (animal) models, the corresponding interpretation of IF measures and how they ultimately translate to humans is unknown. Hence, we studied the scalability of IF across species and sensor platforms. MATERIALS AND METHODS: Scaled values of the two intrinsic frequencies ω1 and ω2 (corresponding to systolic and diastolic dynamics, respectively) were extracted from carotid waveforms acquired either non-invasively (via tonometry, Vivio or iPhone) in humans or invasively in rabbits and rats. KEY FINDINGS: The scaled IF parameters for all species were found to fall within the same physiological ranges carrying similar statistical characteristics, even though body sizes and corresponding heart rates of the species were substantially different. Additionally, results demonstrated that all non-invasive sensor platforms were significantly correlated with each other for scaled IFs, suggesting that such analysis is device-agnostic and can be applied to upcoming wearable technologies. SIGNIFICANCE: Ultimately, our results found that IFs are scalable across species, which is particularly valuable for the training of IF-based artificial intelligence systems using both preclinical and clinical data.