S2 Splitting Research Articles

Identification of S2 Paradoxical Splitting in Aortic Stenosis Subjects via Seismocardiogram Signals From a Wearable Accelerometer Contact Microphone

Second heart sound (S2) splitting can be used as an indicator for diagnosis of cardiovascular diseases; specifically, paradoxical S2 splitting is an indicator of aortic stenosis. We present that S2 acoustic signatures can be captured accurately from the seismocardiogram (SCG) signals of a sensitive wearable accelerometer contact microphone (ACM) and validated by comparing with digital stethoscope phonocardiogram (PCG) signals. The ACM was placed on the pulmonic region of 18 subjects, 10 with no known heart disease and 8 with known heart disease, for 60 seconds of SCG data collection. Smoothed Pseudo Wigner-Ville distribution is used to extract S2 time split and to identify S2 paradoxical splitting. Healthy subjects had SCG S2 time splits range agreeing with S2 time splits from past literature from PCG signals. The ACM SCG signal was al-so used to identify and capture paradoxical splitting from subjects with known valvular heart diseases such as aortic stenosis, from subjects with mild to severe diagnosis. In conclusion, a wearable ACM can be used to detect paradoxical splitting in subjects suspected with aortic valvular heart disease and shows high fidelity of capturing S2 time split through SCG signals.

Noonan Syndrome and Pulmonary Valve Stenosis

Source: Bell JM, Considine EM, McCallen LM, et al. The prevalence of Noonan spectrum disorders in pediatric patients with pulmonary valve stenosis. J Pediatr. 2021;234:134–141.e5; doi:10.1016/j.jpeds.2021.03.050Investigators from the University of Colorado School of Medicine, Denver, CO, and University of Colorado College of Engineering and Applied Science, Boulder, CO, conducted a retrospective study to estimate the prevalence of Noonan spectrum disorders (NSD) in children with pulmonary valve stenosis (PVS), and to identify characteristics that predicted NSD in PVS patients. Study participants were identified using the “Slicer/Dicer” function of the EPIC electronic medical system and included children seen in the Children’s Hospital Colorado Cardiology clinic between 2009 and 2018. The medical records of the identified patients were reviewed, and data on clinical characteristics abstracted. The presence of PVS was confirmed by reviewing echocardiogram reports.Study patients were classified as having NSD based on clinical diagnosis made by a medical geneticist and/or genetic test results. Data on other syndromic conditions present in participants also were recorded. The association of specific other cardiac conditions, including atrial septal defect (ASD), supravalvar pulmonary stenosis (SVPS), ventricular septal defect, hypertrophic cardiomyopathy, and patent ductus arteriosus, with NSD in patients with PVS was assessed by chi square tests. A similar process was used for extracardiac characteristic statistically associated with NSD in children with PVS, including cryptorchidism, lymphedema, hearing loss, pectus deformity, feeding issues, failure to thrive (FTT), developmental delay, short stature, and ocular findings. Bayes rule was used to determine the conditional probability of NSD in patients with one or more of these findings.Data were analyzed on 686 patients with PVS. Of these, a diagnosis of NSD was made in 59 (8.6%), with the diagnosis confirmed by genetic testing in 52 children. Other syndromic conditions were identified in 50 study participants (7.3%); Williams syndrome (N = 8) and trisomy 21 (N = 7) were the most common non-NSD syndromic conditions found. Clinical characteristics statistically significantly associated with a diagnosis of NSD in patients with PVS included lymphedema, cryptorchidism, hearing loss, pectus deformity, feeding issues, FTT, developmental delay, short stature, ocular findings, SVPS, hypertrophic cardiomyopathy, and ASD. Among these characteristics, the strongest predictors of NDS were cryptorchidism (conditional probability, 0.70), pectus deformity (conditional probability, 0.66), and ocular findings (conditional probability, 0.48). For children with PVS, pectus deformity, and developmental delay, the conditional probability of NDS was 0.82.The authors conclude that the prevalence of NSD is high in children with PVS, and that a diagnosis of NSD should be considered in PVS patients with other, specific, clinical characteristics.Dr Spar has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.PVS is the most common type of pulmonary stenosis (characterized by fused commissures with thickened leaflets of the pulmonary valve) and accounts for 8–12% of all CHD.1 PVS can range from mild to critical, with critical being the most severe form of pulmonary stenosis (PS) with inadequate pulmonary blood flow. In NSD the pulmonary valve is dysplastic with prominent leaflet thickening, with a small valve annulus and reduced mobility.2 Typical physical examination findings include an audible click, splitting of S2 and a systolic ejection murmur heard at the second left intercostal space. Echocardiogram confirms diagnosis with visualization of the pulmonary valve anatomy and provides determination of severity of stenosis by measuring the pressure gradient over the pulmonary valve.NSD has autosomal dominant inheritance with significant genetic heterogeneity. The most common pathogenic variants include PTPN11 gene (50% of patients with NSD). There are also at least 17 genes related to encoding of protein of the Ras-MAPK signaling pathway associated with NSD.1,3 Typical clinical manifestations are heterogeneous, with common features including widely spaced eyes, low-set ears, short stature, and PVS.4 Greater than 80% of patients with NSD have cardiac involvement, with the majority having PS and hypertrophic cardiomyopathy.5 Other cardiac lesions seen include ASD, ventricular septal defect, tetralogy of Fallot, pulmonary artery stenosis, coarctation of aorta, and primum type atrial septal defect.3The investigators of the current study reviewed all patients with a diagnosis of PVS without other cardiac lesions over a 10-year period. Patients with a clinical diagnosis after evaluation by a geneticist or confirmed by molecular testing were identified as having NSD. The investigators found that 59 of 686 (8.6%) patients with PVS had NSD. Of the 59, there were 52 children who had a molecular diagnosis, and 6 had a clinical diagnosis. Of patients with PVS, those with NSD were commonly had ASD, hypertrophic cardiomyopathy, and SVPS.PVS is commonly seen in patients with NSD. Genetic evaluation is a consideration in patients with PVS and other features known to be associated with NSD.

Hemodynamics-driven mathematical model of first and second heart sound generation.

We propose a novel, two-degree of freedom mathematical model of mechanical vibrations of the heart that generates heart sounds in CircAdapt, a complete real-time model of the cardiovascular system. Heart sounds during rest, exercise, biventricular (BiVHF), left ventricular (LVHF) and right ventricular heart failure (RVHF) were simulated to examine model functionality in various conditions. Simulated and experimental heart sound components showed both qualitative and quantitative agreements in terms of heart sound morphology, frequency, and timing. Rate of left ventricular pressure (LV dp/dtmax) and first heart sound (S1) amplitude were proportional with exercise level. The relation of the second heart sound (S2) amplitude with exercise level was less significant. BiVHF resulted in amplitude reduction of S1. LVHF resulted in reverse splitting of S2 and an amplitude reduction of only the left-sided heart sound components, whereas RVHF resulted in a prolonged splitting of S2 and only a mild amplitude reduction of the right-sided heart sound components. In conclusion, our hemodynamics-driven mathematical model provides fast and realistic simulations of heart sounds under various conditions and may be helpful to find new indicators for diagnosis and prognosis of cardiac diseases.New & noteworthyTo the best of our knowledge, this is the first hemodynamic-based heart sound generation model embedded in a complete real-time computational model of the cardiovascular system. Simulated heart sounds are similar to experimental and clinical measurements, both quantitatively and qualitatively. Our model can be used to investigate the relationships between heart sound acoustic features and hemodynamic factors/anatomical parameters.

Second heart sound splitting as an indicator of interventricular mechanical dyssynchrony using a novel splitting detection algorithm.

Second heart sound (S2) splitting results from nonsimultaneous closures between aortic (A2) and pulmonic valves (P2) and may be used to detect timing differences (dyssynchrony) in relaxation between right (RV) and left ventricle (LV). However, overlap of A2 and P2 and the change in heart sound morphologies have complicated detection of the S2 splitting interval. This study introduces a novel S‐transform amplitude ridge tracking (START) algorithm for estimating S2 splitting interval and investigates the relationship between S2 splitting and interventricular relaxation dyssynchrony (IRD). First, the START algorithm was validated in a simulated model of heart sound. It showed small errors (<5 ms) in estimating splitting intervals from 10 to 70 ms, with A2/P2 amplitude ratios from 0.2 to 5, and signal‐to‐noise ratios from 10 to 30 dB. Subsequently, the START algorithm was evaluated in a porcine model employing a wide range of paced RV‐LV delays. IRD was quantified by the time difference between invasively measured LV and RV pressure downslopes. Between LV pre‐excitation to RV pre‐excitation, mean S2 splitting interval decreased from 47 ms to 23 ms (p < .001), accompanied by a decrease in mean IRD from 8 ms to −18 ms (p < .001). S2 splitting interval was significantly correlated with IRD in each experiment (p < .001). In conclusion, the START algorithm can accurately assess S2 splitting and may serve as a useful tool to assess interventricular dyssynchrony.

Hoarseness for 1Week.

A 73-year-old woman presented to the emergency department with a 1-week history of hoarseness, dysphagia, and dyspnea. On physical examination, she had jugular vein distension, a harsh systolic murmur at the left upper sternal border, and a significant splitting of S2. Flexible laryngoscopy revealed left vocal cord paralysis (Figure 1A). Chest x-ray study revealed cardiomegaly and dilatation of the main pulmonary artery (Figure 1B). Chest computed tomography showed aneurysmal dilatation of the main pulmonary artery up to 50.8 mm (normative pulmonary artery diameter of 29 mm in men and 27 mm in women) (Figures 1C and 1D).

Second Heart Sound

AbstractThe auscultation of second heart sound reveals presence of the disease and its pathophysiology, conduction defects, ventricular function, and hemodynamics around the aortic and pulmonary valves. To understand the splitting of the second heart sound, it is useful to understand the concepts of hangout interval and ejection time. Differential diagnosis of S2 split include opening snap, third heart sound, and pericardial knock. Variations of second heart sound may involve intensity or variations of split. Variations of split can be single heart sound, wide split, wide fixed split, or paradoxical splitting.Interpretation of second heart sound in congenital heart disease provides information about the presence and position of semilunar valves.

Estimation of the second heart sound split using windowed sinusoidal models

Abstract Knowing the time difference between the onsets of the aortic part (A2) and the pulmonic part (P2) of the second heart sound (S2), also referred to as the time split (TS) of S2, can assist in the diagnosis of a variety of heart diseases. However, estimating the TS is a non-trivial task due to the potential overlap between A2 and P2. In this paper, a model-based approach is proposed where both A2 and P2 are modeled as windowed sinusoids with their sum forming the S2 signal. Estimation of the model parameters and the S2 split form a non-convex optimization problem, where a local minimum is obtained using a sequential optimization procedure. First, the window parameters are found as the solution to a regularized least squares problem. Then, the frequencies and phases of the sinusoids are found by locating the maximal peaks of the heart signals’ frequency magnitudes, and using the corresponding phases. Finally, the TS is estimated as the time difference between the peaks of the cross-correlations between the measured S2 signal and the modeled A2/P2 signals. The algorithm is able to estimate the TS for synthetic signals with a root-mean-square error (RMSE) of 7.6 ms for equidistantly placed TSs between −70 ms and 70 ms. The RMSE increases for small TSs in the interval −30 ms to 10 ms, and at increased noise levels. The algorithm was applied to phonocardiograms recorded from 146 patients, where the average estimated TS was 29.6 ms, in conformance with the average TS of healthy subjects as found in the literature.

Abstract 19011: Initial Field Testing of a Cloud-based Cardiac Auscultation Information Management System in Rural Southwest Kunming Province, Peoples Republic of China

Introduction: Auscultation (Ausc) is used around the world to screen for congenital heart disease (CHD). We describe initial field testing of a cloud-based Ausc information management system in rural China school children with limited access to cardiac care . Our goal is to develop an economical system to facilitate access to cardiac care for underserved children in low- and middle-income countries. Hypothesis: Web/cloud based distant transmission of auscultation exam can facilitate screening for congenital heart disease. Methods: A team of cardiology staff from a tertiary hospital conducted field screening for CHD) in rural school children in Yunnan Province, People’s Republic of China. Each child with a murmur with traditional Ausc underwent echo screening and digital Ausc (Thinklabs, USA). Heart sounds were collected from 5 positions (URSB, ULSB, LLSB, apex and mid-LSB), and uploaded to a server using a tablet application (HeartLink System, USA). Blinded Ausc 3-5 months later was compared with echo finding at on-site screening. Results: 8000 children were screened with standard Ausc over 4 days by a team from Kunming Medical University and First University Hospital. Heart sounds were recorded for 149 subjects. The best vibratory quality of an innocent Still murmur was heard at LLSB in 52,at mid-LSB in 51, apex in 10 and URSB/ULSB in 4. Digital Ausc found pathologic murmurs in 11 of 14 subjects with echo-diagnosed CHD. Three missed were ASD called venous hum in 2 of 3; likely related to respiratory artifact at the URSB/ULSB. Accuracy was 136/149 or 91% with 10 false positive. Positive predictive value 52% and negative predictive value 98%. The graphical phonocardiogram facilitates visual analysis of S2 splitting and the duration and timing of the cardiac murmur. Conclusions: The cloud-based digital Ausc system is able to collect, transmit, organize and display phonocardiograms for remote CHD screening and consultation. Difficulty with respiratory contamination of the signal is noted. VSD and Still murmur were successfully differentiated. The visual phonocardiographic display can aid S2 analysis for splitting. The pilot study demonstrates the potential use of this system to extend pediatric cardiology expertise to underserved rural areas around the world.

Case 3: Respiratory Distress in a 3-Month-Old Boy

1. Nancy Tran, BA* 2. Harold S. Bernstein, MD, PhD† 3. Michael D. Cabana, MD, MPH‡ 1. *University of Vermont College of Medicine, Burlington, VT. 2. †Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY. 3. ‡Departments of Pediatrics, University of California San Francisco, San Francisco, CA. A 3-month-old boy whose parents say that he has been “breathing hard” for 1 day presents to the urgent care clinic. According to his parents, there is no history of fever, cough, or symptoms with feeding. Medical history includes a normal spontaneous vaginal delivery at 39 weeks. Immunizations are up to date. There are no sick contacts. His vital signs are as follows: temperature, 98.2°F (36.8°C); pulse, 168 beats per minute; respiratory rate, 70 breaths per minute; oxygen saturation in the right upper extremity is 100% in room air; and blood pressure was not obtained. Head circumference and length are in the 50th percentile, and weight is at the 25th percentile. On examination, he is well-appearing with adequate perfusion. Lungs are clear to auscultation. Pulses are good in all extremities. Abdomen is soft with a normal liver span. Cardiac examination reveals a hyperdynamic precordium with a rapid heart rate; normal S2 and splitting of S2 could not be heard because of the rapid heart rate. No murmurs or extra sounds are heard. Chest radiography reveals normal cardiothymic silhouette with an ill-defined, hazy opacification within the bilateral bases with obscuration of the right heart border and another opacification of the retrocardiac …

ECG Response: January 14, 2014

ECG Challenge: A 77-year-old man presents for a preoperative evaluation before a hernia repair. He has a history of a previous myocardial infarction (6 years ago), and 2 years ago he underwent cardiac catheterization and a percutaneous coronary intervention because of drug-refractory angina pectoris. Since that time, he has been free of cardiac symptoms, but the surgeon requested a preoperative cardiac evaluation because of his history. Physical examination demonstrates normal heart sounds, but there is a grade 2/6 harsh midsystolic murmur heard at the base with faint radiation to the carotids. It is felt to represent aortic sclerosis. Paradoxical splitting of S2 is also appreciated. The ECG shows a slightly irregular rhythm. The first RR interval is slightly shorter (rate, 64 bpm) than the rest of the RR intervals, which are regular …

A Fourier series based Template Matching Approach to Detect the Splitting of Second Heart Sound

In this paper, we present a method of detecting the splitting of heart sound S2 based on a template matching approach. A mathematical model of normal S2 is created and tested on other normal S2 complexes for goodness of fit. The generalized mathematical model is used as a template for detecting splitting of S2 sounds, as they will not generate a good fit with a model of a normal S2 complex. This automated detection of splitting of S2 can be used in the detection of congenital heart diseases or pulmonary hypertension. We have provided an estimate of the fit results of the mathematically synthesized S2 complex with the split S2 complexes.

Evaluation of computer algorithm performance in culprit artery identification—comparison with expert readers' analysis in acute myocardial infarction

had severe PH (PAM ≥50 mm Hg). All patients had a sinus or paced atrial rhythm. There was a significant correlation coefficient between S2 intensity at the pulmonic area (left upper sternal border) and the PASP (r = 0.34; P = .0097). The correlation between PASP and S4 intensity at the left sternal border was significant (r = 0.37; P = .030). S3 intensity measured from the left sternal border was more weakly associated with PASP (r = 0.28; P = .037). The magnitude or variance of S2 splitting was not associated with PH. Conclusions: Computerized assessment of the S2, S3, and S4 intensities over the right ventricle correlates with invasive measurements of PASP. Further refinement of acoustic cardiography may serve as a noninvasive tool to assess the severity of PH.

Presentation of Congenital Heart Disease in the Neonate and Young Infant

Presentation of Congenital Heart Disease in the Neonate and Young Infant

Heart energy signature spectrogram for cardiovascular diagnosis

A new method and application is proposed to characterize intensity and pitch of human heart sounds and murmurs. Using recorded heart sounds from the library of one of the authors, a visual map of heart sound energy was established. Both normal and abnormal heart sound recordings were studied. Representation is based on Wigner-Ville joint time-frequency transformations. The proposed methodology separates acoustic contributions of cardiac events simultaneously in pitch, time and energy. The resolution accuracy is superior to any other existing spectrogram method. The characteristic energy signature of the innocent heart murmur in a child with the S3 sound is presented. It allows clear detection of S1, S2 and S3 sounds, S2 split, systolic murmur, and intensity of these components. The original signal, heart sound power change with time, time-averaged frequency, energy density spectra and instantaneous variations of power and frequency/pitch with time, are presented. These data allow full quantitative characterization of heart sounds and murmurs. High accuracy in both time and pitch resolution is demonstrated. Resulting visual images have self-referencing quality, whereby individual features and their changes become immediately obvious.

Analysis and study of the variation of splitting in the second heartbeat sound of wavelet transform

The second heart sound, S2, consists of two acoustic components, A2 and P2. The former is due to the closure of the aortic valve and the latter is due to the closure of the pulmonary valve. The aortic valve usually closes before the pulmonary valve, introducing a time delay known as the ‘split’. A technique based on discrete wavelet transform (DWT) and continuous wavelet transform (CWT) is developed in this paper to measure the split. To quantify splitting, two components in S2 (i.e. A2 and P2) are identified, and the delay between the two components can be estimated. One normal case and three pathological cases (mitral stenosis, pulmonary stenosis and atrial septal defect) are considered in this study. The split is measured for each S2 sound of the considered signals. The split normally varies in duration over the cardiac cycle. In certain pathologies such as ASD (atrial septal defect) or PS (pulmonary stenosis), the split becomes fixed over the cardiac cycle. The main part of this paper consists of the identification and measurement of the S2 split. The study confirms the notion of ‘variable splitting’ for normal phonocardiogram and ‘fixed splitting’ for ASD and PS cases. This paper relates also to the establishment of statistical parameters to make a distinction between normal and pathological cases of phonocardiogram signals.

Medicine has become a business, but what is the cost?

Medicine has become a business, but what is the cost?

Phthalonaphthalocyanines: New Far-Red Dyes for Spectral Hole Burning

Mixed phthalocyanines carrying one anthracene (Pc3An) or substituted naphthalene nucleus (Pc3NcR2, R = H, OCH3, or SC12H25) are proposed as low-temperature photochroms for spectral hole burning. Solubility of these compounds in polymers was greatly enhanced by introducing the 2,4-dimethyl-3-pentoxy substituent to the remaining three benzopyrrolic fragments. The wavelengths and intensities of the Q transitions (S1 and S2) were measured for two prototropic tautomers having different position of the pair of inner protons. The average energy of the two lowest transitions is very similar in both tautomers, although the S1−S2 splitting is much smaller in the less stable form. The relative equilibrium concentration of the tautomers at room temperature depends on the electron releasing properties of the substituents. This allows one to predict the positions of protons in each form. Absorption dichroism of stretched polyethylene films was used in order to establish the direction of the S1 and S2 transition dipole moments in the molecular framework. The tautomers can be completely converted into each other at 10 K by light with quantum yields of (1−2) × 10-3 and (5−8) × 10-3, respectively, depending on the direction of the process. Most probably the phototransformation occurs in the vibrationally relaxed triplet state via the tunneling of a single proton which results in an intermediate state with cis-configuration of protons. The photochemically accumulated less stable form decays at higher temperatures (T) as a result of a thermally activated tunneling process at characteristic T of 115 and 153 K for protonated and deuterated Pc3Nc, respectively. The strength of linear electron−photon coupling (EPC), which is crucial from the point of view of spectral hole burning, is characterized by Debye−Waller factors (DWFs) about 0.6−0.75, depending on the compound and the polymer matrix. The T dependence of quasihomogeneous hole width (Γqh) obeys a power law with coefficients 2.5 ± 0.5 (between 6 and 30−45 K). In different polymer hosts, the DWF increases and the hole width decreases in the following order: polystyrene > poly(vinyl butyral) > polyethylene. The strength of EPC for the lowest transitions is similar in both tautomeric forms. A slight enhancement of the EPC strength in the series of dyes Pc3Nc(OCH3)2 ∼ Pc3Nc < Pc3Nc(SC12H25)2 < Pc3An is correlated with the increase of electron-withdrawing power of substituents, plausibly, as a result of the increase of dipole moment change upon electronic excitation. Spectroscopic properties, phototautomerization quantum yields, and the EPC strength of mixed phthalocyanines were compared with those of chlorin and porphyrins.

An investigation of the second heart sound in the normal horse

The second heart sound was evaluated in conscious, normal horses using intracardiac and external sound detection devices and echocardiography. The second heart sound (S2) in the normal horse is single or split by a narrow interval, not usually detected by external phonocardiographic evaluation. Splitting of S2 was classified as normal (aortic [A2] preceding pulmonic [P2] components) in 66.7 per cent and reversed (P2 preceding A2) in 33.3 per cent of the horses studied. Normal splitting appears to result from lower impedance of the pulmonary vasculature delaying the onset of P2. Reverse splitting appears to result from a delay in A2 resulting from prolongation of PEP and LVET. There does not appear to be variation in splitting of S2 due to respiration based on the cases in which this was measured.

Classification of timing and loudness of second heart sound components by expert and novice physicians

Consistent and accurate assessment of the relative timing and loudness of second heart sound (S2) components is essential to skilled performance of cardiac auscultation. Classification of S2 “splitting” and loudness of P2 (the pulmonic component of S2) by expert and novice physicians were examined in experiments designed to minimize the influence of higher order cognitive factors on auscultation performance. Stimuli were recorded heart sounds in which the temporal separation and relative intensity of S2 components were controlled by digital wave form editing. The task was to classify S2 splitting and P2 loudness using categories commonly employed in making chart notation. Experts' responses were more consistent and accurate with respect to detection of underlying pathology than the responses of novices. Perceptual category boundaries for novices varied when the heart rate changed and when a systolic murmur was introduced, while expert boundaries remained stable. Most experts were able to detect asynchrony in S2 components of less than 20 ms. [Work supported by the Graduate School and the Dwan Chair for Education in Pediatric Cardiology at the University of Minnesota.]

Chest wall velocity and the second heart sound. An improved sensor of S2 splitting.

We report a new method of detection of the timing of the aortic and pulmonary valve closure that depends not on the registration of audible vibrations, but rather, on subtle but distinct movements of the chest wall, which are external manifestations of these events. We studied these phenomena in six open-chest dogs and in 69 human subjects. The dog studies show that the two distinct inward movements detected by a motion sensor applied to the epicardium in the vicinity of the right ventricular outflow tract correlate with the timing of the incisural notches of the pressure signals from the great vessels. In humans, these movements are transmitted to the skin surface and can be detected noninvasively. In 48 of the 69 human subjects (70%), these spikes provided a significantly better indication of the timing of semilunar valve closure than did the conventional phonocardiogram.