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

Abstract

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.

Keywords: cardiac imaging and diagnostics; coronary artery disease.

Conflict of interest statement

Competing interests: The current research is financed partly by Acarix A/S by an unrestricted grant. SES is a minor shareholder and part-time consultant in Acarix A/S. BSL is an industrial student at Acarix A/S. MB is part of the Acarix A/S advisory board. MB and SW received an unrestricted institutional research grant from Acarix A/S.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

Flow chart of patients in the study for final diagnosis of CAD. *A CAD-score Version 2 was not calculated in 190 patients and CAD-score Version 3 was not calculated in 204 patients. Median intertest interval from the cardiac CTA to the ICA was 30 days (10th and 90th percentiles: 14 and 50 days). CACS, coronary artery calcium score; CAD, coronary artery disease; CAG, invasive coronary angiography; CTA, CT angiography; FFR, fractional flow reserve; ICA, invasive coronary angiograph; QCA, quantitative coronary angiography.

Figure 2

Depiction of the CAD-score acquisition and the two CAD-score algorithms. The heart sounds were recorded at the fourth intercostal space with patients in a supine position. The preprocessing part of the algorithm organised the heart sounds for analysis through segmentation and filtering. After preprocessing, the acoustic features were extracted from the sounds and an acoustic score was constructed using LDA. In CAD-score Version 3 (V3), the acoustic score was further combined with gender, age and hypertension using logistic regression. AMI, automutal information; FPR, frequency power ratio; HRV, heart rate variability; LDA, linear discriminant analysis; PCARand, principle component analyses-based measure of the randomness; PCASpec, principle component analysis of the diastolic frequency spectrum; S2freq, frequency distribution of the second heart sounds; S4amp, amplitude of the fourth heart sound; SampEn, sample entropy; SpecSlope, slope of diastolic frequency spectrum; SysFPR, systolic frequency power ratio.

Figure 3

CAD-score Version 3 divided by: (A) coronary artery calcium score groups; (B) CAD disease severity defined by cardiac CTA; (C) haemodynamically obstructive coronary vessel disease by cardiac CTA. Box plot illustrated median, IQR and adjacent values.  CACS, coronary artery calcium score; CAD, coronary artery disease; CTA, CT angiography; LM, left main.

Figure 4

The area under the receiver operating characteristic curve for Diamond-Forrester score, acoustic CAD-score Versions 2 and 3, and CAD-score Version 3 with haemodynamically obstructive stenosis diagnosed as reference.

Figure 5

Plots of CAD-score Version 3 accuracy of haemodynamically obstructive coronary stenosis diagnosed with fractional flow reserve (FFR) as reference. Illustrated are a frequency plot, 2×2 table according to a binary CAD-score cut-off >20, and sensitivity and specificity curves with 95% CI bands shown.