Valvular Heart Disease
Impact of Transaortic Valve Flow Velocity on the Development of Systolic Heart Murmurs
2025 Volume 7 Issue 2 Pages 139-142
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2025 Volume 7 Issue 2 Pages 139-142
Background: Although cardiac auscultation plays an essential role in detecting valvular heart diseases, false-positive rates due to innocent heart murmurs remain a concern because accelerated transaortic valve blood flow can be a major contributor to systolic heart murmurs. In this study we investigated the effect of transaortic valve flow velocity on the development of systolic heart murmurs.
Methods and Results: Cardiac auscultation was performed in 571 patients referred for echocardiography and systolic heart murmur was detected in 103 (18.0%). Maximum transaortic valve flow velocity was higher in patients with murmurs than in those without (2.02 vs. 1.34 m/s, P<0.001; area under the receiver operating characteristic curve, 0.82). A cutoff maximum transaortic flow velocity of 1.7 m/s predicted systolic heart murmurs (sensitivity, 65%; specificity, 88%). The incidence of heart murmur was associated with higher maximum transaortic valve flow velocity (<1.7 m/s, 7.3%; 1.7–2.5 m/s, 50.0%; >2.5 m/s, 73.5%). Multivariate analysis revealed the maximum transaortic valve flow velocity as an independent predictor of systolic heart murmurs (hazard ratio, 9.18; 95% confidence interval, 5.35–15.75; P<0.001).
Conclusions: Accelerated transaortic valve flow velocity is an important determinant of systolic heart murmurs. Systolic heart murmurs can be heard before the transaortic valve flow velocity reaches the clinically significant aortic stenosis criterion, which can constitute a considerable number of innocent heart murmurs.
Valvular heart disease is a frequently encountered cardiac disease that imposes a significant burden on the health system.1,2 Early detection of significant valvular dysfunction is important for its proper management,3 but aggressive exploration is required because of the lack of symptoms until the late phase of disease progression.
Cardiac auscultation is the first-line screening procedure for valvular heart disease,4,5 but its clinical significance is affected by its relatively low specificity.6 Echocardiographic exploration has revealed the frequent prevalence of innocent heart murmurs,7,8 the precise mechanism of which has yet to be determined; however, accelerated transaortic valve blood flow can contribute to innocent heart murmurs,9 so in this study we investigated the effect of transaortic valve flow velocity on the development of systolic heart murmurs.
We conducted this prospective study using the institution’s database. Between January and March, 2022, 638 patients underwent echocardiography, of whom we excluded patients with more than moderate aortic (n=16) or mitral (n=20) valve regurgitation or postoperative valvular heart disease (n=31). Consequently, 571 patients were enrolled. Among them, systolic heart murmurs were detected in 103 patients (murmur group), who were compared with those without heart murmurs (n=468, non-murmur group) (Figure 1).
Flowchart of the enrollment of study patients.
Two cardiac sonographers performed the physical examinations. Prior to the start of the study, the sonographers established a routine for performing auscultation before each echocardiography session, resulting in a high level of proficiency in auscultation. In cases of ambiguous heart murmur assessment, a second cardiac sonographer performed additional auscultation to confirm the presence or absence of heart murmurs. Auscultation was performed in a quiet room before echocardiography. This study conformed to the ethical guidelines of the Declaration of Helsinki, and was approved by the Ethics Committee of the International University of Health and Welfare Research (21-Im-068).
EchocardiographyAll patients underwent 2-dimensional transthoracic and Doppler echocardiography while in the left supine position. Echocardiographic parameters were measured according to the American Society of Echocardiography guidelines.10 Valvular heart disease was graded as trivial, mild, moderate, or severe. The velocities of the blood flow passing through the left ventricular outflow tract and aortic valves were also measured. Anatomically anomalous structures were recorded.
Statistical AnalysisWe compared the patients’ characteristics and echocardiograms. Continuous variables are expressed as mean±standard deviation. Fisher’s exact test was used for categorical variables and the unpaired Student’s t-test was used for continuous variables to compare the 2 groups.
Receiver operating characteristic (ROC) curves were used to determine the aortic valve velocities that optimized sensitivity and specificity in predicting the presence of systolic heart murmur. Optimal cutoff values predictive of systolic heart murmur were determined using ROC curves. Logistic regression analysis was performed to identify predictors of systolic heart murmurs. Univariate logistic regression was performed to identify factors influencing systolic murmurs. Predictors with P<0.05 in the univariate analysis were incorporated into the multivariate logistic regression analysis. Statistical significance was set at P<0.05. All statistical analyses were performed with EZR,11 which is for R (i.e., modified version of R commander designed to add statistical functions frequently used in biostatistics).
Patients’ Characteristics and Echocardiographic Data
| Variable | Murmur group | Non-murmur group | P value |
|---|---|---|---|
| n | 103 | 468 | |
| Age (years) | 71.5±10.6 | 64.8±14.6 | <0.001 |
| Male sex | 43 (41.7%) | 225 (48.1%) | 0.275 |
| Body surface area (m2) | 1.58±0.19 | 1.64±0.20 | 0.003 |
| Echocardiographic data | |||
| LVDd (mm) | 43.2±5.7 | 45.4±6.5 | <0.001 |
| LVDs (mm) | 27.2±5.5 | 30.1±7.4 | <0.001 |
| Ejection fraction (%) | 66.7±10.1 | 62.7±12.1 | <0.001 |
| Aortic diameter (mm) | 20.8±2.1 | 21.0±2.0 | 0.28 |
| Cardiac output (L/min) | 5.1±1.2 | 4.7±1.2 | 0.002 |
| AVPG (mmHg) | 18.7±16.0 | 7.7±6.1 | <0.001 |
| AvMax (m/s) | 2.0±0.8 | 1.3±0.4 | <0.001 |
AvMax, maximum transaortic flow velocity; LVDd, left ventricular diastolic dimension; LVDs, left ventricular systolic dimension.
Patients in the murmur group were older (71.5±10.6% vs. 64.8±14.6%, respectively; P<0.001) and body surface area (BSA) was smaller (1.58±0.19 vs. 1.64±0.20 m2, respectively; P=0.003) than in the non-murmur group.
Regarding the echocardiographic data, the murmur group recorded smaller left ventricular diastolic and systolic dimensions (43.2±5.7 vs. 45.4±6.5 mm, P<0.001 and 27.2±5.5 vs. 30.1±7.4 mm, respectively; P<0.001), higher ejection fraction (EF) (66.7±10.1% vs. 62.7±12.1%, respectively; P<0.001), higher aortic valve pressure gradient (AVPG) (18.7±16.0 vs. 7.7±6.1 mmHg, respectively; P<0.001), and higher cardiac output (5.2±1.2 vs. 4.7±1.2L/m2, respectively; P=0.002) than the non-murmur group.
Relationship Between the Maximum Transaortic Valve Flow Velocity (AvMax) and Incidence of Systolic Heart MurmursThe AvMax was significantly faster in the murmur group than in the non-murmur group (2.00 vs. 1.35 m/s, P<0.001). To assess the most accurate cutoff for the AvMax in the prediction of systolic heart murmurs, a ROC curve was generated (Figure 2) and the area under the curve was 0.82. A cutoff AvMax of 1.7 m/s predicted systolic heart murmurs with a sensitivity of 65% and specificity of 88%. Figure 3 shows the relationship between the AvMax and incidence of systolic heart murmur: the incidence of systolic heart murmur increased with a higher AvMax (<1.7 m/s, 7.3%; 1.7–2.5 m/s, 50.0%; >2.5 m/s, 73.5%).
Receiver-operating characteristic curve of the relation between the incidence of systolic heart murmurs and maximum transaortic flow velocity.
Incidence of systolic heart murmurs according to the maximum transaortic flow velocity.
The results of the univariate and multivariate analyses are presented in Table 2. In the univariate analysis, BSA, EF, and aortic diameter exhibited statistically significant differences, but these differences were not significant in the multivariate analysis. In contrast, AvMax showed statistically significant differences in both the univariate and multivariate analyses.
Univariate and Multivariate Predictors of Systolic Heart Murmur
| Variable | Univariate | Multivariate | ||
|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | |
| Body surface area | 0.20 (0.06–0.62) | 0.005 | 0.31 (0.07–1.29) | 0.108 |
| Ejection fraction | 1.04 (1.01–1.06) | 0.002 | 1.02 (0.99–1.04) | 0.104 |
| Aortic diameter | 0.94 (0.84–1.04) | 0.269 | 1.00 (0.87–1.14) | 0.952 |
| AvMax | 10.08 (5.84–17.32) | <0.001 | 9.18 (5.35–15.75) | <0.001 |
AvMax, maximum transaortic flow velocity; CI, confidence interval; OR odds ratio.
In the present study, patients with a systolic heart murmur exhibited a significantly higher AvMax, and the multivariate analysis revealed that a high AvMax was the only predictor of systolic heart murmurs. The incidence of systolic heart murmur was closely related to the AvMax, which suggests that a high AvMax is a major contributor to the development of systolic heart murmurs.
Valvular heart disease is a fatal cardiac disorder that can lead to catastrophic myocardial injury. Early detection and careful observation constitute an integral part of proper management,3 but because of the late onset of cardiac symptoms, mass screening of the general population is required to detect patients in the early phase of the disease.4,5 Auscultation is the gold standard procedure for initial screening, but is known to have a high rate of false-positive results. According to a community-based prospective screening study (OxVALVE), the sensitivity and specificity of auscultation to detect significant valvular heart disease were quite low (44% and 69%, respectively).2 Our echocardiographic investigation suggested significant efficacy of cardiac auscultation as the first-line screening procedure to detect aortic stenosis. The sensitivity and specificity of systolic murmur to detect echocardiographically proven aortic stenosis was 63.2% and 83.5%, respectively. Among our study patients, 82% of echocardiographic studies could have been omitted because of the lack of a systolic murmur. On the other hand, 37% of clinically significant aortic stenosis cases may be overlooked for further investigation. Considering the relatively benign natural course of asymptomatic aortic stenosis, this level of efficacy of cardiac auscultation can be considered acceptable, particularly for restricting the candidates for echocardiographic study.
The precise mechanism underlying heart murmur has not yet been fully elucidated, but the results of the present study identified high flow velocity at the aortic valve as a contributor to systolic heart murmurs. However, the mechanism is considered to be multifactorial, because 7.3% (33/451) of patients with normal AvMax (<1.7 m/s) exhibited systolic heart murmur. In the present study, the murmur group was older, smaller in BSA, and had a smaller heart chamber than the non-murmur group. Sclerotic changes in the aortic valve due to aging,12 small physique that shortens the distance between the stethoscope and heart,13 and valvular regurgitation are factors in the detection of heart murmurs. However, in this study, patients with significant mitral valve regurgitation were excluded to investigate the effect of accelerated ejection of blood flow on the development of systolic heart murmurs. High flow velocity in the left ventricular outflow tract can also contribute to the development of a systolic heart murmur;12 however, in our study, the flow velocity at the aortic valve was always higher than that at the left ventricular outflow tract.
Based on the results of the present study, we specified the threshold of flow velocity causing a systolic heart murmur as 1.7 m/s, which is lower than that of clinically significant aortic valve stenosis (2.5 m/s). More than half (57.7%) of the innocent heart murmurs detected were considered due to high AvMax (1.7–2.5 m/s).
Study LimitationsFirst, participation in this study was restricted to patients who were referred for echocardiographic analysis, which may have resulted in a selection bias. Pediatric patients were excluded, so our results may not apply to pediatric heart murmurs. Second, auscultation is a subjective assessment, and the results are inevitably influenced by the examiner’s skill.
An increase in AvMax was associated with a corresponding increase in the rate of detection of heart murmurs. Thus, AvMax may be a key determinant of systolic heart murmurs. Systolic murmurs may be detected even before the AvMax meets the clinical criteria for significant aortic stenosis, suggesting that a substantial number of these murmurs may be classified as innocent.
None.
The authors declare no conflicts of interest.
International University of Health and Welfare Research Ethics Committee (21-Im-068).
The deidentified participant data will not be shared.
