The CADScor System Frequently asked questions

Transcription

1 1 The CADScor System Frequently asked questions Clinical Usage...2 How can I use the CADScor System?... 2 Contra-indications for use... 2 What is the performance of the CADScor System?... 2 Table: Performance of CADScor System... 3 NPV, PPV, Sensitivity, Specificity... 3 Dependency of the Negative Predictive Value on CAD prevalence Can CADScor System predict where a stenosis is located?... 3 Does the CADScor System detect total occlusions?... 4 Can collateral arteries be detected?... 4 Can CADScor System be used to diagnose high risk subgroups as diabetic patients?... 4 Can I use CADScor System in young patients?... 4 Does CADScor System work in female patients?... 4 What about some borderline cases with a CAD-score slightly above 20?... 4 What factors can influence the CAD-score?... 4 Can I use Betablockers to achieve a lower heart rate?... 4 A patient has had long-term treatment for high blood pressure and has normal BP under medication. Do I consider him hypertensive or not?... 4 Is the CADScor System approved?... 5 In which countries is the CADScor System used?... 5 Which class of CE mark does this belong to?... 5 Operating the CADScor System...5 Where can I find advice for trouble shooting?... 5 What do I do when the battery is low?... 5 Can I talk to my patient during the recording phase?... 5 Can patches be re-used?... 5 Where should I dispose of used patches?... 5 Science...5 What are the main CADScor System Studies?... 5 Algorithm v3 database performance, based on 2260 patients (prevalence 10%), is shown in FAQ Performance of CADScor System and the corresponding Table Schema (manuscript in preparation) How does the algorithm v3 perform with / without clinical risk factors?... 6 Sales...6 Where can I order the system?... 6 What is the delivery time?... 6

2 2 Clinical Usage How can I use the CADScor System? The CADScor System is intended for use as a diagnostic aid in symptomatic patients suspected of stable Coronary Artery Disease. We suggest using the CADScor System as a first-line non-invasive diagnostic aid to rule-out coronary artery disease (CAD) in patients suspected of stable CAD, to avoid further downstream testing and invasive diagnostic procedures. A patient with a low CAD-score ( 20) is highly unlikely to have CAD. A patient with an intermediate (20-29) or high ( 30) CAD-score has increasing likelihood of disease and should be followed more closely or referred for further evaluation. Contra-indications for use Previous coronary artery bypass graft (CABG), previous coronary stenting, arrhythmia causing nonsinus rhythm, implanted donor heart or mechanical heart, implanted mechanical heart pump, implanted pacemaker or cardioverter defibrillator (ICD), implanted electronic equipment in the area above and around the heart, significant operation scars, fragile or compromised skin, abnormal body shape in the fourth left inter-costal (IC4-L)-recording area. The CADScor System performance has not been validated outside the indications for use (symptomatic patients with suspected CAD) or for patients younger than 40 years of age. What is the performance of the CADScor System? Defining CAD as obstructive above 50% diameter stenosis, the sensitivity to identify a patient from all other (with stenosis below 50%) is 88,7%. Specificity is 41.3%. Under these conditions the test has a negative predictive value (NPV) of 97.2% in a 10% CAD prevalence population (see table schema). Data has been calculated from the CADScor System clinical database using the latest algorithm version (algorithm V3 database performance, based on 2260 patient, manuscript in preparation).

3 3 Table: Performance of CADScor System TABLE SCHEMA Prediction positive Prediction negative Condition positive True Positive False Negative Sensitivity Condition negative False Positive True Negative Specificity PPV NPV CAD vs Other*, Threshold=20 CAD-score>20 CAD-score 20 Diagnosis: CAD % (83.6%-92.6%) Diagnosis: Other % (39.2%-43.5%) 13.5% (11.8%-15.4%) 97.2% (95.9%-98.2%) CAD vs NonCAD, Threshold=20 CAD-score>20 CAD-score 20 Diagnosis: CAD % (83.6%-92.6%) Diagnosis: NonCAD % (50.4%-56.6%) 28.1% (24.7%-31.6%) 95.9% (93.9%-97.3%) * Other = NonCAD + insignificant CAD, performance data based on the clinical evaluation report. NPV, PPV, Sensitivity, Specificity Sensitivity is the ability of a test to correctly classify an individual as ʹdiseasedʹ. Specificity is the ability of a test to correctly classify an individual as disease-free. Positive Predictive Value (PPV) is the percentage of patients with a positive test who have the disease. Negative predictive Value (NPV) is the percentage of patients with a negative test who do not have the disease. Positive and negative predictive values are directly related to the prevalence of the disease in the population. Assuming all other factors remain constant, the PPV will increase with increasing prevalence; and NPV increases with decrease in prevalence. Dependency of the Negative Predictive Value on CAD prevalence. The negative predictive value (NPV) of the CAD-score depends on the CAD-prevalence. In a population with lower CAD prevalence the NPV will be higher, and conversely in a high CAD prevalence population, the NPV will be lower. In a patient population with approximately 10% prevalence of CAD, the NPV is > 96% for the CADScor System. If the CAD prevalence is around 5-10% in your patient population, the NPV is at least 97%. The CADScor System is only intended to be used for symptomatic patients, suspected of stable CAD. All patients, despite a CAD-score 20, should be encouraged to consult medical advice if their symptoms persist. Can CADScor System predict where a stenosis is located? No. The CADScor System does not indicate location of stenosis; it predicts with a very high negative predictive value (NPV) that a patient is unlikely to have CAD. However, we see a correlation of the severity of CAD and the CAD-score. The more vessels show stenosis, the higher the CAD-score.

4 4 Does the CADScor System detect total occlusions? A total occlusion does not generate heart sounds from turbulent flow; however other heart sounds generated from an ischaemic heart will contribute to the CAD-score. Can collateral arteries be detected? Collateral arterial supply is the biological response to decreased blood supply to a specific area in the heart. Collateral supply may have overcome the original supply defect, and as such have decreased turbulent flow patterns and aberrant myocardial movement. We do not include specific sound features from collateral arterial supply in the CAD-score. Can CADScor System be used to diagnose high risk subgroups as diabetic patients? Diabetic patients were not excluded in the clinical studies, but data on subgroups is limited. It is however important to stress that the CADScor System is intended for symptomatic patients only, and not as a screening tool in asymptomatic patients despite belonging to a high-risk group for one or more reasons. Can I use CADScor System in young patients? No. The current algorithm is only validated for symptomatic patients above 40 years of age. Does CADScor System work in female patients? Yes. We found no gender difference in our clinical studies. What about some borderline cases with a CAD-score slightly above 20? As CADScor System has a very high negative predictive value, a CAD-score at or below 20 will effectively rule out CAD in the patient. A CAD-score above 20 will on the other hand, indicate that the likelihood of a CAD is increased. What factors can influence the CAD-score? Replicate measurements are normally very similar, but some recording parameters are important, like establishing haemodynamic balance (resting prior to CAD-scoring), or not taking vaso-dilating medicine on the day prior to the measurement (e.g. nitro-glycerine spray or tablets). Can I use Betablockers to achieve a lower heart rate? Yes, as long as they are not the vaso-dilating type. A patient has had long-term treatment for high blood pressure and has normal BP under medication. Do I consider him hypertensive or not? For the algorithm v3 we consider a patient treated for high blood pressure as a hypertension patient. In future algorithms, there might be a refinement.

5 5 Is the CADScor System approved? The CADScor System is approved in Europe (CE mark 2015) and has been sold in selected markets since Q In which countries is the CADScor System used? Currently (mid-2018) the CADScor System is used in Denmark, Sweden, Germany and Austria. Which class of CE mark does this belong to? The CADScor System is a Class 2a device. The patch is a Class 1 device. Operating the CADScor System Where can I find advice for trouble shooting? In section 11 of the CADScor System user manual. What do I do when the battery is low? The system will indicate if the battery is low. The battery consumption is significant during use. 15 minutes charging is sufficient for a couple of recordings, 30 minutes for approx. 10 recordings. Can I talk to my patient during the recording phase? Guiding the patient during the CAD-score evaluation is essential. Two parts of each recording loop exists, one in which the patient is breathing normally, and one in which the patient will hold his/her breath. There must be no talking (or noise) during the breath holding period. Can patches be re-used? No. The patch contains a specific code that is registered and marks the patch as used. Where should I dispose of used patches? The used patches can be disposed of together with other standard clinical waste. Science What are the main CADScor System Studies? In 2015, a study by Winther et al. (Denmark) with 228 patients lead to the approval of the device with algorithm v2 Europe. The study was published in 2016 with a diagnostic performance for diagnosing >50% CAD with 76% sensitivity and 87% NPV (prevalence 28%). Dan-NICAD (Denmark) with 1675 patients was published in 2017 and was the basis for the evolution of algorithm v2 towards algorithm v3 which is performing in the commercial device. The Dan-NICAD population showed a diagnostic performance of 81% sensitivity and 96% NPV for diagnosing > 50% CAD (prevalence 9,3%) The combined database population (prevalence 10%) performs with 88.7% sensitivity and 97% NPV and 2017 VALIDATE (Germany) was performed to gain data outside the intended population

6 6 (high prevalence population) to contribute to the evolution of the algorithm. Currently (July 2018) Dan-NICAD II is ongoing. The CADScor System algorithm Algorithm v3 database performance, based on 2260 patients (prevalence 10%), is shown in FAQ Performance of CADScor System and the corresponding Table Schema (manuscript in preparation). Eight acoustic properties covering four aspects of the heart sound are assessed and subsequently combined with clinical risk factors (age, gender, hypertension) into a CAD-score using logistic regression. Examples of the acoustic properties are the amplitude of the fourth heart sound, the characteristics of the systolic and mid-diastolic heart sound and the frequency distribution of the second heart sound. All of these acoustic signals have been previously described to predict the presence of CAD. How does the algorithm v3 perform with / without clinical risk factors? Dan-NICAD figure 4 illustrates the AUC of the acoustic algorithm v3 with 62% whereas the AUC of the 'entire' algorithm v3 (including sound and risk factors) is 71%. When comparing the acoustic algorithm v3 and the 'entire' algorithm v3, there is no statistically significant difference for the sensitivity and the negative predictive value. The difference for AUC seen in figure 4 is explained by a lower specificity for the acoustic algorithm v3 compared to the 'entire' algorithm v3. This means for the intended exclusion of symptomatic patients with suspected CAD both algorithms perform equally good with respect to NPV and sensitivity. Sales Where can I order the system? Please send an to info@acarix.com. What is the delivery time? You need an introduction / training to use CADScor System. Once you have placed your order, your Acarix representative will contact you to make an appointment to introduce you to the system. He will deliver the system on the day of the training.