Value of acoustic cardiography in the clinical diagnosis of coronary heart disease

Abstract Background To investigate the clinical value of acoustic cardiography in the diagnosis of coronary artery disease (CAD) and post‐percutaneous coronary intervention (PCI) early asymptomatic left ventricular systolic dysfunction. Methods Inpatients in the department of cardiology were included in the research (n = 315); including 180 patients with angina pectoris and 135 patients with acute anterior wall myocardial infarction after emergency PCI did not present with signs and symptoms of heart failure. Color Doppler echocardiography, brain natriuretic peptide, acoustic cardiography examination were performed. The patients were divided into four groups: non‐CAD group (n = 60), CAD group (n = 120), MIREF group (EF% < 50%, n = 75), and MINEF group (EF% ≥ 50%, n = 60). Results Acoustic cardiography parameters EMATc, systolic dysfunction index, S3 strength and S4 strength in the MIREF group were higher than those in MINEF group (p < .05), and the MINEF group was higher than CAD group (p < .05). S3 strength (area under the curve [AUC] 0.67, 95% CI 0.585–0.755, p < .001) and S4 strength (AUC 0.617, 95% CI 0.536–0.698, p = .011) are useful in the diagnosis of CAD. S3 strength (AUC 0.942, 95% CI 0.807–0.978, p < .001) was superior to other indicators in the diagnosis of early left ventricular systolic dysfunction after myocardial infarction. Conclusion S4 combined with STT standard change can improve the diagnosis of CAD. Acoustic cardiography can be used as a non‐invasive, rapid, effective, and simple method for the diagnosis of asymptomatic left ventricular systolic dysfunction in the early stage after myocardial infarction.

characterized by left ventricular enlargement, decreased left ventricular ejection fraction (LVEF) and abnormal regional wall activity, which are the main factors determining the development of further cardiac events and long-term prognosis after acute myocardial infarction (AMI). Asymptomatic left ventricular systolic dysfunction (LVSD) is a major manifestation of early ventricular remodeling, with a prevalence of up to 30%-60% after AMI. Some experts suggest that patients with asymptomatic LVSD after myocardial infarction with an LVEF less than 50% can be diagnosed with ventricular remodeling. [1][2][3][4] Because patients with asymptomatic LVSD often lack typical clinical features, they can easily be overlooked by doctors, resulting in aggravation of the disease. Although B-type brain natriuretic peptide (BNP) and echocardiography can be utilized in the diagnosis of LVSD, they carry several disadvantages including increased cost, the need for professional and technical personnel, and difficulty to achieve dynamic monitoring. Identification of simple, novel parameters that are specific and convenient for predicting coronary artery disease (CAD) is needed, so that appropriate treatments can be initiated as early as possible.
As a result, acoustic cardiography has attracted the attention of researchers as rapid, simple and non-invasive alternative method for the diagnosis of myocardial ischemia and heart failure. Acoustic cardiography has been reported to have clinical value in the diagnosis of heart failure. For example, some studies have shown that cardiac electromechanical activation time (EMAT), left ventricular systolic time (LVST), and S3 are superior to BNP in the diagnosis of LVSD. 5 In addition, other experimental studies have shown that reduction in EMAT is related to left ventricular systolic function and electromechanical delay, and an increase in EMAT% could be predictive for re-admission for heart failure. 6,7 Furthermore, the third and fourth heart sounds (S3 and S4) are less affected by age and diurnal changes, which increases their utility in evaluating cardiac systolic and diastolic function. [8][9][10] There are few clinical studies on the value of acoustic cardiography in the diagnosis of coronary heart disease. Some studies have shown that the evaluation for S3 or S4 combined with ECG increases the detection rate of myocardial ischemia by 32%. 11 When conducting exercise treadmill testing, the use of standard ST-T changes combined with an S4 score >3.6 as the standard for the diagnosis of coronary heart disease resulted in sensitivity and specificity of 68% and 84% respectively. 12  We collected the subjects' general information including age, gender, heart rate, blood pressure, current medications, medical history, standard 12-lead ECG. CAD was defined as horizontal or downsloping ST segment depression ≥0.5 mm in ≥2 contiguous leads or T wave inversion ≥1 mm in ≥2 contiguous leads. Exclusion criteria were as follows: Pre-excitation syndrome, atrial fibrillation, atrioventricular block, intraventricular block, chronic obstructive pulmonary disease(COPD), valvular heart disease, congenital cardiovascular disease, pericarditis, myocarditis, cardiomyopathy, severe liver and kidney disease, mechanical ventilation, cardiac pacemaker. Written informed consent was obtained from each patient prior to participation. The study was approved by the local ethics committees of the participating institutions.

| Acoustic cardiography
Each subject underwent acoustic cardiography examination in a supine position (Figure 1(B)). Acoustic cardiography is a technique that Simultaneous ECG and heart sound data from the V3/V4 standard precordial position were analyzed by the computerized algorithm to calculate the EMAT, S3, S4, systolic dysfunction index (SDI). 13 This algorithm was previously validated by blinded expert interpretation of heart sound tracings. At least three sequential recordings were performed on each study subject and the average value of each variable were used for analysis.
The following acoustic cardiography parameters were evaluated in this study: 1. EMAT: the time from the Q wave onset to the mitral component of the first heart sound (S1). EMATc indicates the proportion of the cardiac cycle occupied by EMAT (Figure 1(A)).
2. Fourth heart sound (S4) strength: the measurement of the intensity and consistency of the S4; one value between 0 and 10 is reported (Figure 1(A)).
3. Third heart sound (S3) strength: the measurement of the intensity and consistency of the S3; one value between 0 and 10 is reported ( Figure 1(A)).  3.2 | Diagnostic characteristics of acoustic cardiography for detecting coronary artery disease ROC curves analysis was used to determine the value of various acoustic cardiographic parameters for predicting CAD. As shown in Figure 2 and 3.3 | Diagnostic characteristics of acoustic cardiography for detecting AMI with early asymptomatic left ventricular systolic dysfunction Figure 3 displays the ROC curve analyses of various acoustic cardiography parameters and BNP for predicting AMI with early EALVSD. Figure 3 and Table 3 15,16 In general, our study indicates that S4 strength combined with ST-T changes of the ECG can improve the diagnosis of coronary heart disease. We did not use fractional flow reserve (FFR) as a diagnostic criterion for myocardial ischemia. It is the limitation of our experiment. The reason that we did not evaluate myocardial ischemia using FFR was that FFR is usually performed in our hospital when the coronary artery is about 75%. When it is significantly less than or more than 75%, generally, it will not be considered, which may be out of consideration for operation time, patients' safety, drug safety, and so on.
In clinical practice, AMI often causes heart failure, in particular within the week following the acute event. Although emergency PCI can reduce the incidence of arrhythmia, cardiogenic shock and heart failure following AMI, there are still some patients who suffer from heart failure. and elevated left ventricular filling pressure. 17 The performance of acoustic cardiography to diagnose acute heart failure (sensitivity and specificity of S3 ≥ 5.0 + %EMAT ≥ 14.4% were 69% and 100%, respectively) was better than BNP in the "gray zone" of 100 pg/ml < BNP < 500 pg/ml. 18 Additional studies show that SDI is more sensitive and specific in the diagnosis of heart failure with LVEF ≤35%, while S3 has high sensitivity and specificity in the diagnosis of diastolic heart failure. 19 In the follow-up observation of patients with chronic heart failure, the patients with SDI ≥5 or S3 strength ≥4 had increased mortality.
Acoustic cardiography can predict the prognosis of patients with chronic heart failure, and be used for adjustment of the patient's treatment plan based on the results of EMAT to significantly reduce adverse events. The monitoring of night time EMAT is a method to predict adverse events of acute heart failure with results better than hemodynamic monitoring. [20][21][22][23] Other studies show that monitoring with acoustic cardiography can be used as a fast, simple, and effective method to predict early systolic dysfunction and to screen patients with sleep apnea syndrome. [24][25][26] In conclusion, S4 strength combined with ST-T changes of the ECG can improve the diagnosis of coronary heart disease; Acoustic cardiography can be used as a fast, simple, inexpensive and effective method to diagnose asymptomatic LVSD in the early weeks after AMI.

| LIMITATIONS OF THE STUDY
The sample size of this study was small; larger studies are needed to confirm these findings. Only the ejection fraction was recorded during echocardiographic examination which did not allow exploration of other cardiac parameters. We did not use FFR as a diagnostic criterion for myocardial ischemia. It is the limitation of our experiment, in subsequent experiment, we will improve the evaluation and diagnostic criteria of myocardial ischemia.

ACKNOWLEDGMENTS
We gratefully thank the patients who participated in our study.
Siliangyi, Chenmoshui and other research staff of Division of

CONFLICT OF INTEREST
The authors declare that they have no conflicts of interest.

DATA AVAILABILITY STATEMENT
All data generated or analysed during this study are included in this published article .The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.