Assessment of Cardiac Function and Prevalence of Sleep Disordered Breathing Using Ambulatory Monitoring With Acoustic Cardiography – Initial Results From Swicos

The aim of this study was to assess the use of ambulatory acoustic cardiography during the initial data collection of the longitudinal study of a rural population in Switzerland (n=297, mean age 48.9 ±16.5 years, 57% female). Ambulatory acoustic cardiography non-invasively can assess sleep disordered breathing (SDB) and provides markers of left ventricular systolic and diastolic dysfunction. The percentage of the third heart sound detected during sleep decreased significantly across age groups (age < 40 years, 40-60 years, > 60 years) for both genders (males, p=0.04; females, p=0.02). The percentage of a fourth heart sound detected exhibited an increasing trend for both genders with age suggesting increased diastolic dysfunction with aging. Mean electromechanical activation time (EMAT) during sleep was within the normal range across age groups and both genders (male 93.7 ± 11.6 ms, female 94.6 ± 13.0 ms), and did not vary significantly with age. A large proportion of subjects had a high likelihood of sleep disordered breathing (17.6%). Baseline characteristics categorized by SDB severity indicate increasing age, male gender and being overweight (BMI ≥ 25) to be associated with greater SDB severity. Acoustic cardiography findings categorized by SDB severity reveal increased nocturnal non-dipping heart rate, presence of atrial fibrillation, prolonged QRS duration and QTc interval, increased percentage of fourth heart sound detected, and longer EMAT to be significantly associated with greater SDB severity. Overall, acoustic cardiography detected a very low prevalence of systolic dysfunction, age-related increases in diastolic dysfunction and a moderate prevalence of sleep disordered breathing. DOI : 10.14302/issn.2329-9487.jhc-18-1932 Freely Available Online www.openaccesspub.org JHC CC-license DOI : 10.14302/issn.2329-9487.jhc-18-1932 Vol-2 Issue 3 Pg. no.– 33 Introduction The life expectancy in Switzerland is particularly high and due, in part, to nationwide patient management strategies aimed at lowering blood pressure [1] and controlling hyperlipidemia to decrease the number of deaths due to acute coronary disease [2] and stroke, but cardiovascular disease remains the leading cause of mortality and morbidity. The longitudinal SWICOS cohort study [3] is intended to examine and longitudinally follow health status and disease risk factors in select rural Swiss populations to support development of new implementable and successful preventive strategies for healthy ageing. In addition to conventional epidemiological parameters of cardiovascular health, SWICOS uses contemporary technologies including ambulatory acoustic cardiography monitoring [4] as part of the establishment of a well-defined database of health status. Acoustic cardiography evaluation involves a 24-hour ambulatory Holter-type recording performed using a device that stores continuous ECG, heart sound and respiratory data (AUDICOR, Inovise Medical, Inc., Beaverton, Oregon, USA). Analysis of the acoustic cardiography recording results in parameters to evaluate diastolic function, in particular, the presence of a fourth heart sound (S4), which has been shown to be associated with increased left ventricular stiffness [5]. Acoustic cardiography also produces parameters to assess systolic function including the presence of a third heart sound (S3) shown to be correlated with elevated filling pressure [6], electromechanical activation time (EMAT) that reflects the time required for the left ventricle to generate enough pressure to close the mitral valve [7] and the Systolic Dysfunction Index (SDI, a composite score of ECG and heart sound parameters). In addition, ambulatory monitoring with acoustic cardiography produces an automated measure of the severity of sleep-disordered breathing [8]. Results from ambulatory acoustic cardiography have previously been reported on small asymptomatic [9] and heart failure populations [10]. Lausanne, Switzerland has been the setting for a population-based survey of cardiovascular risk factors (CoLaus) [11] and, separately, at-home sleep disordered breathing assessment (HypnoLaus) [12]. However, little data exists on the associations between sleep disordered breathing and left ventricular systolic / diastolic function within a rural Swiss population. The aim of this study was to assess the applicability of the use of acoustic cardiography in voluntary participants of the recently begun longitudinal study of a rural population in Switzerland. In this paper we report only the acoustic cardiography findings for the initial data collection to evaluate systolic and diastolic heart function and sleep disorders. Materials and Methods Ambulatory acoustic cardiographic Holter data were collected between April, 2015 and January, 2017 from residents within the region of Cama, Switzerland age 15 years and older that were willing to participate long-term in the SWICOS study. There were no exclusion criteria. The study received approval from the ethics committee of Nordwest und Zentralschweiz (reference number EKNZ 2014-209; NCT02282748). Informed consent was obtained from all subjects. Anamnestic data was obtained through questionnaire and interview of the subject. Patient height and weight were measured during initial examination. Corresponding author: Paul Erne, MD, FESC, Faculty of Biomedical Sciences, Universita della Svizzera Italiana, Via Giuseppe Buffi 13, CH-6094, Lugano, Switzerland; ; Phone: +41 79 628 45 46; Fax: +41 44 634 49 86. E-Mail: paul.erne@erne-net.ch Running title: Initial SWICOS Results from Ambulatory Monitoring


Introduction
The life expectancy in Switzerland is particularly high and due, in part, to nationwide patient management strategies aimed at lowering blood pressure [1] and controlling hyperlipidemia to decrease the number of deaths due to acute coronary disease [2] and stroke, but cardiovascular disease remains the leading cause of mortality and morbidity. The longitudinal SWICOS cohort study [3] is intended to examine and longitudinally follow health status and disease risk factors in select rural Swiss populations to support development of new implementable and successful preventive strategies for healthy ageing. In addition to conventional epidemiological parameters of cardiovascular health, SWICOS uses contemporary technologies including ambulatory acoustic cardiography monitoring [4] as part of the establishment of a well-defined database of health status.
Acoustic cardiography evaluation involves a 24-hour ambulatory Holter-type recording performed using a device that stores continuous ECG, heart sound and respiratory data (AUDICOR, Inovise Medical, Inc., Beaverton, Oregon, USA). Analysis of the acoustic cardiography recording results in parameters to evaluate diastolic function, in particular, the presence of a fourth heart sound (S4), which has been shown to be associated with increased left ventricular stiffness [5].
Acoustic cardiography also produces parameters to assess systolic function including the presence of a third heart sound (S3) shown to be correlated with elevated filling pressure [6], electromechanical activation time (EMAT) that reflects the time required for the left ventricle to generate enough pressure to close the mitral valve [7] and the Systolic Dysfunction Index (SDI, a composite score of ECG and heart sound parameters).
In addition, ambulatory monitoring with acoustic cardiography produces an automated measure of the severity of sleep-disordered breathing [8].
Results from ambulatory acoustic cardiography have previously been reported on small asymptomatic [9] and heart failure populations [10]. Lausanne, Switzerland has been the setting for a population-based survey of cardiovascular risk factors (CoLaus) [11] and, separately, at-home sleep disordered breathing assessment (HypnoLaus) [12]. However, little data exists on the associations between sleep disordered breathing and left ventricular systolic / diastolic function within a rural Swiss population.
The aim of this study was to assess the applicability of the use of acoustic cardiography in voluntary participants of the recently begun longitudinal study of a rural population in Switzerland. In this paper we report only the acoustic cardiography findings for the initial data collection to evaluate systolic and diastolic heart function and sleep disorders.

Materials and Methods
Ambulatory acoustic cardiographic Holter data were collected between April, 2015 and January, 2017 from residents within the region of Cama, Switzerland age 15 years and older that were willing to participate long-term in the SWICOS study. There were no exclusion criteria. The study received approval from the ethics committee of Nordwest und Zentralschweiz (reference number EKNZ 2014-209; NCT02282748).
Informed consent was obtained from all subjects. Anamnestic data was obtained through questionnaire and interview of the subject. Patient height and weight were measured during initial examination.

Acoustic Cardiographic Holter Recordings
The ambulatory acoustic cardiography recording was obtained by placing standard ECG electrodes in modified limb locations and dual-purpose ECG / sound AUDICOR sensors placed in either the standard V4 position or both the V3 and V4 precordial positions while the subject was in a supine position (Figure 1). The main AUDICOR recording device was secured on the upper chest wall using two standard ECG snap-type electrodes. Adequate quality of the ECG and heart sound signals was confirmed visually by study personnel before starting the recording. Simultaneous ECG, heart sound and respiration data were recorded simultaneously for the duration of the recording and partitioned into awake and sleep periods.
The ECG signals were overread by trained Holter technicians for ectopy and rhythm abnormalities.
Automated analysis of the ECG data produced results for QRS duration, QTc interval and heart rate.
The ECG and heart sound data underwent

Discussion
The results provided in this paper represent the acoustic cardiography results from the initial data collection (n=297) of the longitudinal SWICOS study conducted in the region of Cama, Switzerland. Recent studies have shown that both short (typically < 5-6 hours) and long (typically >8-9 hours) durations of sleep are associated with increased mortality, obesity and risk of CVD. The mean sleep time (4.9 ± 1.5 hours) for our population would be regarded as "short" in duration with no significant differences related to gender or aging.

Cappuccio et al. have shown that short sleep duration is
associated with greater risk of developing or dying of coronary heart disease or stroke [15], and Ford [16] reported increased 10-year risk of CVD with short sleep duration (14.5%). Our results suggest the need for lifestyle modifications and public education to improve sleep duration to reduce cardiovascular risk.
Although considered physiologic in those under 40 years, the presence of a diastolic third heart sound has been shown to identify patients with more advanced heart failure [17] and has been associated with adverse outcomes in both heart failure and acute myocardial infarction [18,19]. The S3 occurs in diastole during early passive filling and is caused by the sudden deceleration of rapid filling into a distended or stiff ventricle [20]. Using acoustic cardiography on short recordings, detection of a third heart sound has been correlated to elevated LV end-diastolic pressure and reduced ejection fraction [21], and in emergency department patients with signs or symptoms of acute decompensated heart failure has been found to be specific for primary heart failure [22].   over a mean follow-up period of 43 months. The nondipping heart rate group had significantly more cardiovascular events including stroke, heart failure and ischemic heart disease and the presence of non-dipping was independently associated with the incidence of CVD.
Limitations of this study include the small number of participants in this first data collection so that more complete subgroup analysis by age and gender is not possible. Additional statistical analyses after stratification by SDB or BMI are also not possible due to small subgroup sizes. Echocardiographic parameters were not collected during the patient assessment, thus not allowing acoustic cardiography parameters to be correlated to conventional measures of LV systolic and diastolic function obtained in the same patient. Acoustic cardiographic analysis is limited in two ways. First, the acoustic cardiography analysis depends upon the quality of the ECG signal such that poor ECG signal due to artifact or other noise may reduce the analysis yield in the same way it does in regular ECG Holter analyses.
Second, acoustic cardiography measurements are not calculated for heart rates greater than 150 bpm, which has not been a problem in this study population.