Seismocardiography as a tool for assessment of bi-ventricular pacing.

Objective.Conduction-induced heart failure in patients with left bundle branch block (LBBB) can benefit from cardiac resynchronization therapy (CRT). However, some patients are non-responders to the therapy with one contributing factor being poor optimization of the atrioventricular (AV) pacing delay. In this study, we have investigated the pacing-induced changes in the seismocardiogram (SCG).Approach.14 patients with heart failure, LBBB, and CRT were included. SCG was recorded with pacing turned on and off. Based on a mean SCG heartbeat from each patient, fiducial points were annotated, and cardiac timing intervals (CTI) and amplitudes were derived. These were compared between the CRT group and a group of healthy normal subjects (n= 14). Echocardiography was also used to derive CTI. Intervals derived from the SCG and echocardiogram were correlated.Main results.The isovolumetric contraction time (IVCT) derived from SCG was significantly shorter in the CRT group when the pacemaker was turned on (63.2-52.6 ms,p= 0.027). The first peak-to-peak amplitude in the systolic complex was significantly larger with the pacemaker turned on (p= 0.002), as well as the ∣max-min∣ amplitude in the systolic complex (p= 0.003). Isovolumetric relaxation time and left ventricular ejection time (LVET) were not significantly different between pacemaker settings. Compared to normal subjects, IVCT was significantly prolonged with the pacemaker turned off. All amplitudes were significantly larger in the healthy subject group. IVCT and LVET derived from SCG were significantly correlated to the echocardiogram.Significance.IVCT shortened and SCG amplitudes increased in response to CRT, indicating a more efficient ventricular contraction. This demonstrates the possibility to detect cardio-mechanic changes in response to treatment with the SCG. However, for the patients the systolic part of the SCG was abnormal and difficult to characterize, raising concerns about the correct interpretation of the SCG.

Coronary Artery Disease Detected by Low Frequency Heart Sounds.

OBJECTIVES: Previous studies have observed an increase in low frequency diastolic heart sounds in patients with coronary artery disease (CAD). The aim was to develop and validate a diagnostic, computerized acoustic CAD-score based on heart sounds for the non-invasive detection of CAD. METHODS: Prospective study enrolling 463 patients referred for elective coronary angiography. Pre-procedure non-invasive recordings of heart sounds were obtained using a novel acoustic sensor. A CAD-score was defined as the power ratio between the 10-90 Hz frequency spectrum and the 90-300 Hz frequency spectrum of the mid-diastolic heart sound. Quantitative coronary angiography analysis was performed by a blinded core laboratory and patients grouped according to the results: obstructive CAD defined by the presence of at least one ≥ 50% stenosis, non-obstructive CAD as patients with a maximal stenosis in the 25-50% interval and non-CAD as no coronary lesions exceeding 25%. We excluded patients with potential confounders or incomplete data (n = 245). To avoid over-fitting the final cohort of 218 patients was randomly divided into to a training group for development (n = 127) and a validation group (n = 91). RESULTS: In both the training and the validation group the CAD-score was significantly increased in CAD patients compared to non-CAD patients (p < 0.0001). In the validation group the area under the receiver-operating curve was 77% (95% CI 63-91%). Sensitivity was 71% (95% CI 59-82%) and specificity 64% (95% CI 45-83%). CONCLUSION: The acoustic CAD-score is a new, inexpensive, non-invasive method to detect CAD, which may supplement clinical risk stratification and reduce the need for subsequent non-invasive and invasive testing.

Improved pre-test likelihood estimation of coronary artery disease using phonocardiography.

Aims: Current early risk stratification of coronary artery disease (CAD) consists of pre-test probability scoring such as the 2019 ESC guidelines on chronic coronary syndromes (ESC2019), which has low specificity and thus rule-out capacity. A newer clinical risk factor model (risk factor-weighted clinical likelihood, RF-CL) showed significantly improved rule-out capacity over the ESC2019 model. The aim of the current study was to investigate if the addition of acoustic features to the RF-CL model could improve the rule-out potential of the best performing clinical risk factor models. Methods and results: Four studies with heart sound recordings from 2222 patients were pooled and distributed into two data sets: training and test. From a feature bank of 40 acoustic features, a forward-selection technique was used to select three features that were added to the RF-CL model. Using a cutoff of 5% predicted risk of CAD, the developed acoustic-weighted clinical likelihood (A-CL) model showed significantly (P < 0.05) higher specificity of 48.6% than the RF-CL model (specificity of 41.5%) and ESC 2019 model (specificity of 6.9%) while having the same sensitivity of 84.9% as the RF-CL model. Area under the curve of the receiver operating characteristic for the three models was 72.5% for ESC2019, 76.7% for RF-CL, and 79.5% for A-CL. Conclusion: The proposed A-CL model offers significantly improved rule-out capacity over the ESC2019 model and showed better overall performance than the RF-CL model. The addition of acoustic features to the RF-CL model was shown to significantly improve early risk stratification of symptomatic patients suspected of having stable CAD.

Spectral analysis of heart sounds associated with coronary artery disease.

Objective. The aim of this study was to find spectral differences of diagnostic interest in heart sound recordings of patients with coronary artery disease (CAD) and healthy subjects.Approach. Heart sound recordings from three studies were pooled, and patients with clear diagnostic outcomes (positive: CAD and negative: Non-CAD) were selected for further analysis. Recordings from 1146 patients (191 CAD and 955 Non-CAD) were analyzed for spectral differences between the two groups using Welch's spectral density estimate. Frequency spectra were estimated for systole and diastole segments, and time-frequency spectra were estimated for first (S1) and second (S2) heart sound segments. An ANCOVA model with terms for diagnosis, age, gender, and body mass index was used to evaluate statistical significance of the diagnosis term for each time-frequency component.Main results. Diastole and systole segments of CAD patients showed increased energy at frequencies 20-120 Hz; furthermore, this difference was statistically significant for the diastole. CAD patients showed decreased energy for the mid-S1 and mid-S2 segments and conversely increased energy before and after the valve sounds. Both S1 and S2 segments showed regions of statistically significant difference in the time-frequency spectra.Significance. Results from analysis of the diastole support findings of increased low-frequency energy from previous studies. Time-frequency components of S1 and S2 sounds showed that these two segments likely contain heretofore untapped information for risk assessment of CAD using phonocardiography; this should be considered in future works. Further development of features that build on these findings could lead to improved acoustic detection of CAD.

Advanced heart sound analysis as a new prognostic marker in stable coronary artery disease.

Aims: Recent technological advances enable diagnosing of obstructive coronary artery disease (CAD) from heart sound analysis with a high negative predictive value. However, the prognostic impact of this approach remains unknown. To investigate the prognostic value of heart sound analysis as two scores, the Acoustic-score and the CAD-score, in patients with suspected CAD which is treated according to standard of care. Methods and results: Consecutive patients with angina symptoms referred for coronary computed tomography angiography (CTA) were enrolled. The Acoustic-score was developed from eight acoustic CAD-related features. This score was combined with risk factors to generate the CAD-score. A cut-off score >20 was pre-specified for both scores to indicate disease. If coronary CTA raised suspicion of obstructive CAD, patients were referred to invasive angiography and revascularized when indicated. Of 1675 enrolled patients, 1464 (87.4%) were included in this substudy. The combined primary endpoint was all-cause mortality and myocardial infarction (n = 26). Follow-up was 3.1 (2.7-3.4) years. Of patients with primary endpoints, the Acoustic-score was >20 in 25 (96%); the CAD-score was >20 in 22 (85%). In an unadjusted Cox analysis of the primary endpoints, the hazard ratio for scores >20 under current standard clinical care was 12.6 (1.7-93.2) for the Acoustic-score and 5.4 (1.9-15.7) for the CAD-score. The CAD-score contained prognostic information even after adjusting for lipid-lowering therapy initiation, stenosis at CTA, and early revascularization. Conclusion: Heart sound analysis seems to carry prognostic information and may improve initial risk stratification of patients with suspected CAD. Clinicaltrialsorg ID: NCT02264717.

Multichannel seismocardiography: an imaging modality for investigating heart vibrations.

OBJECTIVE: Seismocardiography is the measurement of vibration waves caused by the beating heart with accelerometer(s) placed on the chest. Investigating the nature and the behavior of these vibration waves, by comparing measurements from multiple sites, would help to understand the heart's mechanical contraction activity. APPROACH: Using newly designed multichannel seismocardiogram equipment, it was possible to investigate the vibration waves with 16 three-axis sensors. The equipment performed well with highly precise synchronization rate over 10 min, linear frequency response and high signal quality. The vibration waves were analyzed using the sagittal axis, a single cardiac cycle and focusing on four fiducial points. Two of the fiducial point where the negative and positive peaks associated with aorta valve opening, along with peaks associated with aorta valve closing. MAIN RESULTS: The respective average centers of mass of the four fiducial points in 13 subjects were at (frontal axis: 35 mm, vertical axis: 5 mm), (31, 6), (26, 24), and (4, -2), relative to the Xiphoid Process. Similar patterns among the subjects were identified for the propagation of the waves across the chest for the four fiducial points. SIGNIFICANCE: The multichannel seismocardiogram equipment successfully revealed a general pattern present in chest surface vibration maps.

Author Correction: Definition of Fiducial Points in the Normal Seismocardiogram.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Contractile Fronts In The Interventricular Septum: A Case For High Frame Rate Echocardiographic Imaging.

The real time high frame rate (HFR) 2-dimensional ultrasound system, T5, at Duke University is capable of imaging at up to 1000 images per second for adult cardiac imaging. A method for detecting and visualizing the mechanical contraction fronts using HFR echocardioagraphy-derived Strain Rate Image (SRI) was described in 26 patients. The Tissue Shortening Onset front durations for echocardiographic normal patients were significantly shorter than conduction disorder patients with left bundle branch block (LBBB) with intrinsic conduction and conduction disorder patients without LBBB (non-LBBB) with simulated LBBB (sLBBB). Echocardiographic normal patients had significantly higher correlation coefficients between their SRIs and spatially inverted versions of themselves compared to non-LBBB patients with intrinsic conduction and sLBBB. In conclusion, SRIs could spatially resolve contractile event fronts in patients.

A Clinical Method for Estimation of VO2max Using Seismocardiography.

The purpose of this study was to investigate the correlation between the seismocardiogram and cardiorespiratory fitness. Cardiorespiratory fitness can be estimated as VO2max using non-exercise algorithms, but the results can be inaccurate. Healthy subjects were recruited for this study. Seismocardiogram and electrocardiogram were recorded at rest. VO2max was measured during a maximal effort cycle ergometer test. Amplitudes and timing intervals were extracted from the seismocardiogram and used in combination with demographic data in a non-exercise prediction model for VO2max. 26 subjects were included, 17 females. Mean age: 38.3±9.1 years. The amplitude following the aortic valve closure derived from the seismocardiogram had a significant correlation of 0.80 (p<0.001) to VO2max. This feature combined with age, sex and BMI in the prediction model, yields a correlation to VO2max of 0.90 (p<0.001, 95% CI: 0.83-0.94) and a standard error of the estimate of 3.21 mL·kg-1·min-1 . The seismocardiogram carries information about the cardiorespiratory fitness. When comparing to other non-exercise models the proposed model performs better, even after cross validation. The model is limited when tracking changes in VO2max. The method could be used in the clinic for a more accurate estimation of VO2max compared to current non-exercise methods.

Long-Term Prognostic Value of Less-Stringent Electrocardiographic Q Waves and Fourth Universal Definition of Myocardial Infarction Q Waves.

BACKGROUND: The Fourth Universal Definition of Myocardial Infarction defines electrocardiographic Q waves as duration ≥30 ms and amplitude ≥1 mm or QS complex in 2 contiguous leads. However, current taskforce criteria may be overly restrictive. Therefore, we investigated the association of isolated, lenient, or strict Q waves with long-term outcome. METHODS: From 2001 to 2015, we included Danish primary care patients with digital electrocardiograms (ECGs) that were evaluated for Q waves. If none occurred, patients had no Q waves. If no other contiguous Q wave occurred, patients had isolated Q waves. If another contiguous Q wave occurred meeting only 1 criterion (≥30 ms and <1 mm or <30 ms and ≥1 mm), patients had lenient Q waves. If another contiguous Q wave occurred, patients had strict Q waves. RESULTS: Of 365,206 patients, 87,957 had isolated, lenient, or strict Q waves (24%; median age, 61 years; male, 48%), and 277,249 had no Q waves (76%; median age, 53 years; male, 42%). Mortality risk was increased with isolated (all-cause adjusted hazard ratio [aHR], 1.33; 95% confidence interval [CI], 1.29-1.37; cardiovascular-cause aHR, 1.78; 95% CI, 1.70-1.87), lenient (all-cause aHR, 1.41; 95% CI, 1.33-1.50; cardiovascular-cause aHR, 1.78; 95% CI, 1.63-1.94), or strict (all-cause aHR, 1.64; 95% CI, 1.57-1.72; cardiovascular-cause aHR, 2.70; 95% CI, 2.52-2.89) Q waves compared with no Q waves. Highest mortality risk was associated with lenient or strict Q waves in anteroseptal leads. CONCLUSIONS: This large contemporary analysis suggests that less-stringent Q-wave criteria carry prognostic value in predicting adverse outcome among primary care patients.

Comparison of Different Methods for Estimating Cardiac Timings: A Comprehensive Multimodal Echocardiography Investigation.

Cardiac time intervals are important hemodynamic indices and provide information about left ventricular performance. Phonocardiography (PCG), impedance cardiography (ICG), and recently, seismocardiography (SCG) have been unobtrusive methods of choice for detection of cardiac time intervals and have potentials to be integrated into wearable devices. The main purpose of this study was to investigate the accuracy and precision of beat-to-beat extraction of cardiac timings from the PCG, ICG and SCG recordings in comparison to multimodal echocardiography (Doppler, TDI, and M-mode) as the gold clinical standard. Recordings were obtained from 86 healthy adults and in total 2,120 cardiac cycles were analyzed. For estimation of the pre-ejection period (PEP), 43% of ICG annotations fell in the corresponding echocardiography ranges while this was 86% for SCG. For estimation of the total systolic time (TST), these numbers were 43, 80, and 90% for ICG, PCG, and SCG, respectively. In summary, SCG and PCG signals provided an acceptable accuracy and precision in estimating cardiac timings, as compared to ICG.

Associations between common ECG abnormalities and out-of-hospital cardiac arrest.

Background: Out-of-hospital cardiac arrest (OHCA) is often the first manifestation of unrecognised cardiac disease. ECG abnormalities encountered in primary care settings may be warning signs of OHCA. Objective: We examined the association between common ECG abnormalities and OHCA in a primary care setting. Methods: We cross-linked individuals who had an ECG recording between 2001 and 2011 in a primary care setting with the Danish Cardiac Arrest Registry and identified OHCAs of presumed cardiac cause. Results: A total of 326 227 individuals were included and 2667 (0,8%) suffered an OHCA. In Cox regression analyses, adjusted for age and sex, the following ECG findings were strongly associated with OHCA: ST-depression without concomitant atrial fibrillation (HR 2.79; 95% CI 2.45 to 3.18), left bundle branch block (LBBB; HR 3.44; 95% CI 2.85 to 4.14) and non-specific intraventricular block (NSIB; HR 3.15; 95% CI 2.58 to 3.83). Also associated with OHCA were atrial fibrillation (HR 1.89; 95% CI 1.63 to 2.18), Q-wave (HR 1.75; 95% CI 1.57 to 1.95), Cornell and Sokolow-Lyon criteria for left ventricular hypertrophy (HR 1.56; 95% CI 1.33 to 1.82 and HR 1.27; 95% CI 1.12 to 1.45, respectively), ST-elevation (HR 1.40; 95% CI 1.09 to 1.54) and right bundle branch block (HR 1.29; 95% CI 1.09 to 1.54). The association between ST-depression and OHCA diminished with concomitant atrial fibrillation (HR 1.79; 95% CI 1.42 to 2.24, p < 0.01 for interaction). Among patients suffering from OHCA, without a known cardiac disease at the time of the cardiac arrest, 14.2 % had LBBB, NSIB or ST-depression. Conclusions: Several common ECG findings obtained from a primary care setting are associated with OHCA.

Quantitative Parameters of High-Frame-Rate Strain in Patients with Echocardiographically Normal Function.

Recently, we developed a high-frame-rate echocardiographic imaging system capable of acquiring images at rates up to 2500 per second. High imaging rates were used to quantify longitudinal strain parameters in patients with echocardiographically normal function. These data can serve as a baseline for comparing strain parameters in disease states. The derived timing data also reveal the propagation of mechanical events in the left ventricle throughout the cardiac cycle. High-frame-rate echocardiographic images were acquired from 17 patients in the apical four-chamber view using Duke University's phased array ultrasound system, T5. B-Mode images were acquired at 500-1000 images per second by employing 16:1 or 32:1 parallel processing in receive, a scan depth ≤14 cm and an 80° field of view with a 3.5-MegaHertZ (MHz), 96-element linear array. The images were analyzed using a speckle tracking algorithm tailored for high-frame-rate echocardiographic images developed at Aalborg and Duke University. Four specific mechanical events were defined using strain curves from six regions along the myocardial contour of the left ventricle. The strain curves measure the local deformation events of the myocardium and are independent of the overall cardiac motion. We observed statistically significant differences in the temporal sequence among different myocardial segments for the first mechanical event described, myocardial tissue shortening onset (p < 0.01). We found that the spatial origin of tissue shortening was located near the middle of the interventricular septum in patients with echocardiographically normal function. The quantitative parameters defined here, based on high-speed strain measurements in patients with echocardiographically normal function, can serve as a means of assessing degree of contractile abnormality in the myocardium and enable the identification of contraction propagation. The relative timing pattern among specific events with respect to the Q wave may become an important new metric in assessing cardiac function and may, in turn, improve diagnosis and prognosis.

Definition of Fiducial Points in the Normal Seismocardiogram.

The purpose of this work is to define fiducial points in the seismocardiogram (SCG) and to correlate them with physiological events identified in ultrasound images. For 45 healthy subjects the SCG and the electrocardiogram (ECG) were recorded simultaneously at rest. Immediately following the SCG and ECG recordings ultrasound images of the heart were also obtained at rest. For all subjects a mean SCG signal was calculated and all fiducial points (peaks and valleys) were identified and labeled in the same way across all signals. Eight physiologic events, including the valve openings and closings, were annotated from ultrasound as well and the fiducial points were correlated with those physiologic events. A total of 42 SCG signals were used in the data analysis. The smallest mean differences (±SD) between the eight events found in the ultrasound images and the fiducial points, together with their correlation coefficients (r) were: atrial systolic onset: -2 (±16) ms, r = 0.75 (p < 0.001); peak atrial inflow: 13 (±19) ms, r = 0.63 (p < 0.001); mitral valve closure: 4 (±11) ms, r = 0.71 (p < 0.01); aortic valve opening: -3 (±11) ms, r = 0.60 (p < 0.001); peak systolic inflow: 13 (±23) ms, r = 0.42 (p < 0.01); aortic valve closure: -5 (±12) ms, r = 0.94 (p < 0.001); mitral valve opening: -7 (±19) ms, r = 0.87 (p < 0.001) and peak early ventricular filling: -18 (±28 ms), r = 0.79 (p < 0.001). In conclusion eight physiologic events characterizeing the cardiac cycle, are associated with reproducible, well-defined fiducial points in the SCG.

An Intraneural Electrode for Bioelectronic Medicines for Treatment of Hypertension.

OBJECTIVES: As the left vagus nerve (LVN) mediates a baroreflex blood pressure (BP) decrease, LVN stimulation (LVNS) could be a therapy for hypertension. Moreover, LVNS could elegantly be adjusted to the patient's actual BP and physical activity by using the neural information about BP and respiration extractable from LVN. However, unselective LVNS will trigger undesirable side-effects and therefore we here investigated the feasibility of using an intraneural electrode for extracting BP and respiration markers from the LVN and for selective LVNS. MATERIALS AND METHODS: Experiments were performed on six anesthetized pigs from which the BP was recorded using arterial catheters and the respiratory cycles by recording the airway pressure. An electrode comprising four tripolar channels was inserted longitudinally in the LVN of the animals to extract BP and respiration markers from the LVN and for selective LVNS. RESULTS: BP-related and respiratory-related neural profiles (BPnPs and RnPs, respectively) were derived from at least two electrode channels in all pigs. The BPnPs accurately resembled the BP waves and the RnPs accurately resembled the respiratory cycles, which suggests that those profiles could serve as BP and respiration markers, respectively. The BP was decreased by intraneural LVNS in all pigs and in four of those pigs such an effect was induced without major cardiac changes through a channel-selective stimulation. CONCLUSION: This study shows that it is feasible to extract BP and respiratory markers from the LVN with the tested intraneural electrode and suggests that this electrode could also be used for selective LVNS.

A Respiratory Marker Derived From Left Vagus Nerve Signals Recorded With Implantable Cuff Electrodes.

OBJECTIVE: Left vagus nerve (LVN) stimulation (LVNS) has been tested for lowering the blood pressure (BP) in patients with resistant hypertension (RH). Whereas, closed-loop LVNS (CL-LVNS) driven by a BP marker may be superior to open-loop LVNS, there are situations (e.g., exercising) when hypertension is normal. Therefore, an ideal anti-RH CL-LVNS system requires a variable to avoid stimulation in such conditions, for example, a respiratory marker ideally extracted from the LVN. As the LVN conducts respiratory signals, this study aimed to investigate if such signals can be recorded using implantable means and if a marker to monitor respiration could be derived from such recordings. MATERIALS AND METHODS: The experiments were performed in 14 anesthetized pigs. Five pigs were subjected to changes of the respiratory frequency and nine to changes of the respiratory volume. The LVN electroneurogram (VENG) was recorded using two cuff electrodes and the respiratory cycles (RC) using a pressure transducer. To separate the afferent and efferent VENGs, vagotomy was performed between the cuffs in the first group of pigs. The VENG was squared to derive respiration-related neural profiles (RnPs) and their correlation with the RCs was investigated in regard to timing and magnitude parameters derived from the two waveforms. RESULTS: The RnPs were morphologically similar with the RCs and the average RnPs represented accurate copies of the average RCs. Consequently, the lung inflation/deflation RC and RnP components had the same duration, the respiratory frequency changes affected in the same way both waveforms and the RnP amplitude increased linearly with the lung inflation in all tested pigs (R2 values between 0.85 and 0.99). CONCLUSIONS: The RnPs comprise information regarding the timing and magnitude of the respiratory parameters. As those LVN profiles were derived using implantable means, this study indicates that the RnPs could serve as respiratory markers in implantable systems.

A History of Drug-Induced Torsades de Pointes Is Associated With T-wave Morphological Abnormalities.

The hypothesis of the study is that Torsades de pointes (TdP) history can be better identified using T-wave morphology compared to Fridericia-corrected QT interval (QTcF) at baseline. ECGs were recorded at baseline and during sotalol challenge in 20 patients with a history of TdP (+TdP) and 16 patients without previous TdP (-TdP). The QTcF and T-wave morphology combination score (MCS) were calculated. At baseline, there was no significant difference in QTcF between the groups (+TdP: QTcF = 446 ± 9 ms; -TdP: QTcF = 431 ± 9 ms, P = 0.27). In contrast, MCS was significantly different between the groups at baseline (+TdP: MCS = 1.07 ± 0.095; -TdP: MCS = 0.74 ± 0.07, P = 0.012). Both QTcF and MCS could be used to discriminate between +TdP and -TdP after sotalol but only MCS reached statistical significance at baseline. Combining QTcF with MCS provided a significantly larger difference between groups than QTcF alone.

Diagnostic performance of an acoustic-based system for coronary artery disease risk stratification.

OBJECTIVE: Diagnosing coronary artery disease (CAD) continues to require substantial healthcare resources. Acoustic analysis of transcutaneous heart sounds of cardiac movement and intracoronary turbulence due to obstructive coronary disease could potentially change this. The aim of this study was thus to test the diagnostic accuracy of a new portable acoustic device for detection of CAD. METHODS: We included 1675 patients consecutively with low to intermediate likelihood of CAD who had been referred for cardiac CT angiography. If significant obstruction was suspected in any coronary segment, patients were referred to invasive angiography and fractional flow reserve (FFR) assessment. Heart sound analysis was performed in all patients. A predefined acoustic CAD-score algorithm was evaluated; subsequently, we developed and validated an updated CAD-score algorithm that included both acoustic features and clinical risk factors. Low risk is indicated by a CAD-score value ≤20. RESULTS: Haemodynamically significant CAD assessed from FFR was present in 145 (10.0%) patients. In the entire cohort, the predefined CAD-score had a sensitivity of 63% and a specificity of 44%. In total, 50% had an updated CAD-score value ≤20. At this cut-off, sensitivity was 81% (95% CI 73% to 87%), specificity 53% (95% CI 50% to 56%), positive predictive value 16% (95% CI 13% to 18%) and negative predictive value 96% (95% CI 95% to 98%) for diagnosing haemodynamically significant CAD. CONCLUSION: Sound-based detection of CAD enables risk stratification superior to clinical risk scores. With a negative predictive value of 96%, this new acoustic rule-out system could potentially supplement clinical assessment to guide decisions on the need for further diagnostic investigation. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT02264717; Results.

Association between maternal vascular murmur and the small-for-gestational-age fetus with abnormal umbilical artery Doppler flow.

OBJECTIVE: To investigate the association between maternal vascular murmurs (MVMs) and fetal growth restriction (defined as small-for-gestational-age [SGA] fetus) and abnormal Doppler pulsatility index (PI) of the uterine and/or umbilical arteries. METHODS: A cross-sectional study of women aged 18 years or older with a singleton pregnancy at 28-34 weeks was conducted at Regional Hospital Viborg, Denmark, between May 1 and August 1, 2013. Ultrasound fetal biometry was performed and the Doppler PI of the umbilical and uterine arteries was determined. An estimated fetal weight (EFW) at or below the 10th percentile was defined as SGA. Microphone recordings from the lower abdomen were divided into heart valve sounds and MVMs. RESULTS: The final analysis included 63 participants, with 25 classified as SGA and 38 as non-SGA. The mean pregnancy duration was 32.4 ± 1.4 weeks. In total, 17 participants had MVMs. There was a clear association between MVMs and a composite of SGA and an abnormal PI of the uterine and/or the umbilical artery (P<0.001), but not between MVMs and SGA only (P=0.154). CONCLUSION: Maternal vascular murmurs are significantly associated with fetal growth restriction, but not with SGA per se.