Smartphone-based screening for atrial fibrillation: a pragmatic randomized clinical trial.

Digital smart devices have the capability of detecting atrial fibrillation (AF), but the efficacy of this type of digital screening has not been directly compared to usual care for detection of treatment-relevant AF. In the eBRAVE-AF trial ( NCT04250220 ), we randomly assigned 5,551 policyholders of a German health insurance company who were free of AF at baseline (age 65 years (median; interquartile range (11) years, 31% females)) to digital screening (n = 2,860) or usual care (n = 2,691). In this siteless trial, for digital screening, participants used a certified app on their own smartphones to screen for irregularities in their pulse waves. Abnormal findings were evaluated by 14-day external electrocardiogram (ECG) loop recorders. The primary endpoint was newly diagnosed AF within 6 months treated with oral anti-coagulation by an independent physician not involved in the study. After 6 months, participants were invited to cross-over for a second study phase with reverse assignment for secondary analyses. The primary endpoint of the trial was met, as digital screening more than doubled the detection rate of treatment-relevant AF in both phases of the trial, with odds ratios of 2.12 (95% confidence interval (CI), 1.19-3.76; P = 0.010) and 2.75 (95% CI, 1.42-5.34; P = 0.003) in the first and second phases, respectively. This digital screening technology provides substantial benefits in detecting AF compared to usual care and has the potential for broad applicability due to its wide availability on ordinary smartphones. Future studies are needed to test whether digital screening for AF leads to better treatment outcomes.

Telemedical cardiac risk assessment by implantable cardiac monitors in patients after myocardial infarction with autonomic dysfunction (SMART-MI-DZHK9): a prospective investigator-initiated, randomised, multicentre, open-label, diagnostic trial.

BACKGROUND: Cardiac autonomic dysfunction after myocardial infarction identifies patients at high risk despite only moderately reduced left ventricular ejection fraction. We aimed to show that telemedical monitoring with implantable cardiac monitors in these patients can improve early detection of subclinical but prognostically relevant arrhythmic events. METHODS: We did a prospective investigator-initiated, randomised, multicentre, open-label, diagnostic trial at 33 centres in Germany and Austria. Survivors of acute myocardial infarction with left ventricular ejection fraction of 36-50% had biosignal analysis for assessment of cardiac autonomic function. Patients with abnormal periodic repolarisation dynamics (≥5·75 deg2) or abnormal deceleration capacity (≤2·5 ms) were randomly assigned (1:1) to telemedical monitoring with implantable cardiac monitors or conventional follow-up. Primary endpoint was time to detection of serious arrhythmic events defined by atrial fibrillation 6 min or longer, atrioventricular block class IIb or higher and fast non-sustained (>187 beats per min; ≥40 beats) or sustained ventricular tachycardia or fibrillation. This study is registered with ClinicalTrials.gov, NCT02594488. FINDINGS: Between May 12, 2016, and July 20, 2020, 1305 individuals were screened and 400 patients at high risk were randomly assigned (median age 64 years [IQR 57-73]); left ventricular ejection fraction 45% [40-48]) to telemedical monitoring with implantable cardiac monitors (implantable cardiac monitor group; n=201) or conventional follow-up (control group; n=199). During median follow-up of 21 months, serious arrhythmic events were detected in 60 (30%) patients of the implantable cardiac monitor group and 12 (6%) patients of the control group (hazard ratio 6·33 [IQR 3·40-11·78]; p<0·001). An improved detection rate by implantable cardiac monitors was observed for all types of serious arrhythmic events: atrial fibrillation 6 min or longer (47 [23%] patients vs 11 [6%] patients; p<0·001), atrioventricular block class IIb or higher (14 [7%] vs 0; p<0·001) and ventricular tachycardia or ventricular fibrillation (nine [4%] patients vs two [1%] patients; p=0·054). INTERPRETATION: In patients at high risk after myocardial infarction and cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction, telemedical monitoring with implantable cardiac monitors was highly effective in early detection of subclinical, prognostically relevant serious arrhythmic events. FUNDING: German Centre for Cardiovascular Research (DZHK) and Medtronic Bakken Research Center.

Periodic Repolarization Dynamics Identifies ICD Responders in Nonischemic Cardiomyopathy: A DANISH Substudy.

BACKGROUND: Identification of patients with nonischemic cardiomyopathy who may benefit from prophylactic implantation of a cardioverter-defibrillator. We hypothesized that periodic repolarization dynamics (PRD), a marker of repolarization instability associated with sympathetic activity, could be used to identify patients who will benefit from prophylactic implantable cardioverter defibrillator (ICD) implantation. METHODS: We performed a post hoc analysis of DANISH (Danish ICD Study in Patients With Dilated Cardiomyopathy), in which patients with nonischemic cardiomyopathy, left ventricular ejection fraction (LVEF) ≤35%, and elevated NT-proBNP (N-terminal probrain natriuretic peptides) were randomized to ICD implantation or control group. Patients were included in the PRD substudy if they had a 24-hour Holter monitor recording at baseline with technically acceptable ECG signals during the night hours (00:00-06:00). PRD was assessed using wavelet analysis according to previously validated methods. The primary end point was all-cause mortality. Cox regression models were adjusted for age, sex, NT-proBNP, estimated glomerular filtration rate, LVEF, atrial fibrillation, ventricular pacing, diabetes, cardiac resynchronization therapy, and mean heart rate. We proposed PRD ≥10 deg2 as an exploratory cut-off value for ICD implantation. RESULTS: A total of 748 of the 1116 patients in DANISH qualified for the PRD substudy. During a mean follow-up period of 5.1±2.0 years, 82 of 385 patients died in the ICD group and 85 of 363 patients died in the control group (P=0.40). In Cox regression analysis, PRD was independently associated with mortality (hazard ratio [HR], 1.28 [95% CI, 1.09-1.50] per SD increase; P=0.003). PRD was significantly associated with mortality in the control group (HR, 1.51 [95% CI, 1.25-1.81]; P<0.001) but not in the ICD group (HR, 1.04 [95% CI, 0.83-1.54]; P=0.71). There was a significant interaction between PRD and the effect of ICD implantation on mortality (P=0.008), with patients with higher PRD having greater benefit in terms of mortality reduction. ICD implantation was associated with an absolute mortality reduction of 17.5% in the 280 patients with PRD ≥10 deg2 (HR, 0.54 [95% CI, 0.34-0.84]; P=0.006; number needed to treat=6), but not in the 468 patients with PRD <10 deg2 (HR, 1.17 [95% CI, 0.77-1.78]; P=0.46; P for interaction=0.01). CONCLUSIONS: Increased PRD identified patients with nonischemic cardiomyopathy in whom prophylactic ICD implantation led to significant mortality reduction.

Estimation of anaerobic threshold by cardiac repolarization instability: a prospective validation study.

BACKGROUND: Assessing lactate (LT) or anaerobic thresholds (AT) in athletes is an important tool to control training intensities and to estimate individual performance levels. Previously we demonstrated that ECG-based assessment of cardiac repolarization instability during exercise testing allows non-invasive estimation of AT in recreational athletes. Here, we validate this method in professional and amateur team sports athletes. METHODS: We included 65 team sports athletes (32 professionals and 33 amateur athletes; 51 men, 14 women, mean age 22.3 ± 5.2 years) undergoing a standardized incremental cycle exercise test. During exercise testing a high-resolution ECG (1000 Hz) was recorded in Frank-leads configuration and beat-to-beat vector changes of cardiac repolarization (dT°) were assessed by previously established technologies. Repolarization-based AT (ATdT°) was estimated by its typical dT°-signal pattern. Additionally, LT was detected in accordance to methods established by Mader (LTMader) and Dickhuth (LTDickhuth). RESULTS: All athletes performed exercise testing until exhaustion with a mean maximum workload of 262.3 ± 60.8 W (241.8 ± 64.4 W for amateur athletes and 283.4 ± 49.5 W for professional athletes). Athletes showed ATdT° at 187.6 ± 44.4 W, LTDickhuth at 181.1 ± 45.6 W and LTMader at 184.3 ± 52.4 W. ATdT° correlated highly significantly with LTDickhuth (r = 0.96, p < 0.001) and LTMader (r = 0.98, p < 0.001) in the entire cohort of athletes as well as in the subgroups of professional and amateur athletes (p < 0.001 for all). CONCLUSIONS: ATdT°, defined by the maximal discordance between dT° and heart rate, can be assessed reliably and non-invasively via the use of a high-resolution ECG in professional and amateur athletes.

Rationale and design of a digital trial using smartphones to detect subclinical atrial fibrillation in a population at risk: The eHealth-based bavarian alternative detection of Atrial Fibrillation (eBRAVE-AF) trial.

Current guidelines recommend opportunistic screening for subclinical atrial fibrillation (AF) taking advantage of e-health-based technologies. However, the efficacy of a fully scalable e-health-based strategy for AF detection in a head-to-head comparison with routine symptom-based screening is unknown. eBRAVE-AF is an investigator-initiated, digital, prospective, randomized, siteless, open-label, cross-over study to evaluate an e-health-based strategy for detection of AF in a real-world setting. 67,488 policyholders of a large German health insurance company (Versicherungskammer Bayern, Germany) selected by age ≥ 50 years and a CHA2DS2-VASc score ≥ 1 (females ≥2) are invited to participate. Subjects with known AF or on treatment with oral anticoagulation are excluded. After obtaining electronic informed consent, at least 4,400 participants will be randomly assigned to an e-health-based screening strategy or routine symptom-based screening. The e-health-based strategy consists of repetitive one-minute photoplethysmographic (PPG) pulse wave assessments using a certified smartphone app (Preventicus Heartbeats, Preventicus, Jena, Germany), followed by a confirmatory 14-day ECG patch (CardioMem CM 100 XT, Getemed, Teltow, Germany) in case of abnormal findings. After 6 months, participants are crossed over to the other study arm. Primary endpoint is the incidence of newly diagnosed AF leading to oral anticoagulation indicated by an independent physician. Clinical follow-up will be at least 12 months. In both groups, follow-up is performed by 4-week app-based questionnaires, personal contact in case of abnormal findings, and matching with claim-based insurance data and medical reports. At time of writing enrollment is completed. First results are expected to be available in mid-2021.

Discontinuation versus continuation of renin-angiotensin-system inhibitors in COVID-19 (ACEI-COVID): a prospective, parallel group, randomised, controlled, open-label trial.

BACKGROUND: SARS-CoV-2 entry in human cells depends on angiotensin-converting enzyme 2, which can be upregulated by inhibitors of the renin-angiotensin system (RAS). We aimed to test our hypothesis that discontinuation of chronic treatment with ACE-inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) mitigates the course o\f recent-onset COVID-19. METHODS: ACEI-COVID was a parallel group, randomised, controlled, open-label trial done at 35 centres in Austria and Germany. Patients aged 18 years and older were enrolled if they presented with recent symptomatic SARS-CoV-2 infection and were chronically treated with ACEIs or ARBs. Patients were randomly assigned 1:1 to discontinuation or continuation of RAS inhibition for 30 days. Primary outcome was the maximum sequential organ failure assessment (SOFA) score within 30 days, where death was scored with the maximum achievable SOFA score. Secondary endpoints were area under the death-adjusted SOFA score (AUCSOFA), mean SOFA score, admission to the intensive care unit, mechanical ventilation, and death. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT04353596. FINDINGS: Between April 20, 2020, and Jan 20, 2021, 204 patients (median age 75 years [IQR 66-80], 37% females) were randomly assigned to discontinue (n=104) or continue (n=100) RAS inhibition. Within 30 days, eight (8%) of 104 died in the discontinuation group and 12 (12%) of 100 patients died in the continuation group (p=0·42). There was no significant difference in the primary endpoint between the discontinuation and continuation group (median [IQR] maximum SOFA score 0·00 (0·00-2·00) vs 1·00 (0·00-3·00); p=0·12). Discontinuation was associated with a significantly lower AUCSOFA (0·00 [0·00-9·25] vs 3·50 [0·00-23·50]; p=0·040), mean SOFA score (0·00 [0·00-0·31] vs 0·12 [0·00-0·78]; p=0·040), and 30-day SOFA score (0·00 [10-90th percentile, 0·00-1·20] vs 0·00 [0·00-24·00]; p=0·023). At 30 days, 11 (11%) in the discontinuation group and 23 (23%) in the continuation group had signs of organ dysfunction (SOFA score ≥1) or were dead (p=0·017). There were no significant differences for mechanical ventilation (10 (10%) vs 8 (8%), p=0·87) and admission to intensive care unit (20 [19%] vs 18 [18%], p=0·96) between the discontinuation and continuation group. INTERPRETATION: Discontinuation of RAS-inhibition in COVID-19 had no significant effect on the maximum severity of COVID-19 but may lead to a faster and better recovery. The decision to continue or discontinue should be made on an individual basis, considering the risk profile, the indication for RAS inhibition, and the availability of alternative therapies and outpatient monitoring options. FUNDING: Austrian Science Fund and German Center for Cardiovascular Research.

Impact of acute ethanol intake on cardiac autonomic regulation.

Acute alcohol consumption may facilitate cardiac arrhythmias underlying the 'Holiday Heart Syndrome'. Autonomic imbalance is promoting atrial arrhythmias. We analyzed the effects of alcohol on measures of the cardiac autonomic nervous system and their relation to arrhythmias. In 15 healthy individuals, alcohol was administered parenterally until a breath alcohol concentration of 0.50 mg/l. High-resolution digital 30-min ECGs were recorded at baseline, at the time of maximum alcohol concentration, and after alcohol concentration returned to near baseline. Using customized software, we assessed periodic repolarization dynamics (PRD), deceleration capacity (DC), standard measures of heart rate variability (SDNN; RMSSD; LF; HF), and standard ECG parameters (mean heart rate; PQ; QRS; QTc interval). At the maximum alcohol concentration, PRD levels were significantly increased compared to baseline [1.92 (IQR 1.14-3.33) deg2 vs. 0.85 (0.69-1.48) deg2; p = 0.001]. PRD levels remained slightly increased when alcohol concentrations returned to baseline. DC levels were significantly decreased at the maximum alcohol concentration compared to baseline [7.79 (5.89-9.62) ms vs. 9.97 (8.20-10.99) ms; p = 0.030], and returned to baseline levels upon reaching baseline levels of alcohol. Standard HRV measures were reduced at maximum alcohol concentration. The mean heart rate increased significantly during alcohol administration. QRS and QTc duration were significantly prolonged, whereas PQ interval showed no change. Our findings revealed an increase of sympathetic activity and a reduction of parasympathetic activity under the influence of alcohol administration, resulting in autonomic imbalance. This imbalance might ultimately trigger arrhythmias underlying the 'Holiday Heart Syndrome'.

Deceleration Capacity and Periodic Repolarization Dynamics As Predictors of Acute Mountain Sickness.

Hamm, Wolfgang, Sari Kassem, Lukas von Stülpnagel, Florian Maier, Mathias Klemm, Dominik Schüttler, Felix Grabher, Ludwig T. Weckbach, Bruno C. Huber, Axel Bauer, Konstantinos D. Rizas, and Stefan Brunner. Deceleration capacity and periodic repolarization dynamics as predictors of acute mountain sickness. High Alt Med Biol. 21:417-422, 2020. Background: The autonomic nervous system plays an important role in adaptive changes after acute altitude exposure. Periodic repolarization dynamics (PRD) and deceleration capacity (DC) of heart rate are advanced electrocardiogram (ECG)-based parameters reflecting sympathetic (PRD) and parasympathetic (DC) tone. These parameters have not been investigated in the context of acute mountain sickness (AMS) yet. Methods: In 23 healthy individuals (13 women), a high-resolution digital 30-minute ECG in Frank leads configuration was performed in a resting supine position at baseline (521 m altitude) and after a sojourn of 24 hours at the Environmental Research Station Schneefernerhaus (UFS) at Zugspitze (2,650 m altitude). PRD and DC were assessed using validated software. Symptoms of AMS were assessed with the Lake Louise Acute Mountain Sickness Score (LLS). Results: During altitude exposure, PRD significantly increased from 1.50 ± 1.01 (mean ± standard deviation) deg2 to 3.51 ± 4.46 deg2 (p = 0.03). DC significantly decreased from 11.48 ± 2.91 ms to 9.94 ± 2.78 ms (p = 0.001). An increase of PRD and/or a decrease of DC correlated significantly with the level of LLS. The combined finding of an increase of PRD and a decrease of DC had a sensitivity of 100% and a specificity of 76.5% to diagnose AMS (LLS ≥3). Receiver operating characteristic (ROC) analysis showed an AUC (area under the ROC curve) of 0.77. Linear regression analysis revealed a significant association between LLS and an increase in PRD during high-altitude exposure. Conclusions: Our findings show an increase of PRD and a decrease of DC during altitude exposure. Combined PRD and DC analysis may have potential for the diagnosis of AMS.

Effect of Hyperventilation on Periodic Repolarization Dynamics.

Heart and lung functions are closely connected, and the interaction is mediated by the autonomic nervous system. Hyperventilation has been demonstrated to especially activate its sympathetic branch. However, there is still a lack of methods to assess autonomic activity within this cardiorespiratory coupling. Periodic repolarization dynamics (PRD) is an ECG-based biomarker mirroring the effect of efferent cardiac sympathetic activity on the ventricular myocardium. Its calculation is based on beat-to-beat variations of the T wave vector (dT°). In the present study, we investigated the effects of a standardized hyperventilation maneuver on changes of PRD and its underlying dT° signal in 11 healthy subjects. In response to hyperventilation, dT° revealed a characteristic pattern and normalized dT° values increased significantly compared to baseline [0.063 (IQR 0.032) vs. 0.376 (IQR 0.093), p < 0.001] and recovery [0.082 (IQR 0.029) vs. 0.376 (IQR 0.093), p < 0.001]. During recovery, dT° remained on a higher level compared to baseline (p = 0.019). When calculating PRD, we found significantly increased PRD values after hyperventilation compared to baseline [3.30 (IQR 2.29) deg2 vs. 2.76 (IQR 1.43) deg2, p = 0.018]. Linear regression analysis revealed that the increase in PRD level was independent of heart rate (p = 0.63). Our pilot data provide further insights in the effect of hyperventilation on sympathetic activity associated repolarization instability.

Cardiovascular Mortality Can Be Predicted by Heart Rate Turbulence in Hemodialysis Patients.

BACKGROUND: Excess mortality in hemodialysis patients is mostly of cardiovascular origin. We examined the association of heart rate turbulence (HRT), a marker of baroreflex sensitivity, with cardiovascular mortality in hemodialysis patients. METHODS: A population of 290 prevalent hemodialysis patients was followed up for a median of 3 years. HRT categories 0 (both turbulence onset [TO] and slope [TS] normal), 1 (TO or TS abnormal), and 2 (both TO and TS abnormal) were obtained from 24 h Holter recordings. The primary end-point was cardiovascular mortality. Associations of HRT categories with the endpoints were analyzed by multivariable Cox regression models including HRT, age, albumin, and the improved Charlson Comorbidity Index for hemodialysis patients. Multivariable linear regression analysis identified factors associated with TO and TS. RESULTS: During the follow-up period, 20 patients died from cardiovascular causes. In patients with HRT categories 0, 1 and 2, cardiovascular mortality was 1, 10, and 22%, respectively. HRT category 2 showed the strongest independent association with cardiovascular mortality with a hazard ratio of 19.3 (95% confidence interval: 3.69-92.03; P < 0.001). Age, calcium phosphate product, and smoking status were associated with TO and TS. Diabetes mellitus and diastolic blood pressure were only associated with TS. CONCLUSION: Independent of known risk factors, HRT assessment allows identification of hemodialysis patients with low, intermediate, and high risk of cardiovascular mortality. Future prospective studies are needed to translate risk prediction into risk reduction in hemodialysis patients.

Prediction of mortality benefit based on periodic repolarisation dynamics in patients undergoing prophylactic implantation of a defibrillator: a prospective, controlled, multicentre cohort study.

BACKGROUND: A small proportion of patients undergoing primary prophylactic implantation of implantable cardioverter defibrillators (ICDs) experiences malignant arrhythmias. We postulated that periodic repolarisation dynamics, a novel marker of sympathetic-activity-associated repolarisation instability, could be used to identify electrically vulnerable patients who would benefit from prophylactic implantation of ICDs by way of a reduction in mortality. METHODS: We did a prespecified substudy of EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD), a prospective, investigator-initiated, non-randomised, controlled cohort study done at 44 centres in 15 EU countries. Patients aged 18 years or older with ischaemic or non-ischaemic cardiomyopathy and reduced left ventricular ejection fraction (≤35%) were eligible for inclusion if they met guideline-based criteria for primary prophylactic implantation of ICDs. Periodic repolarisation dynamics from 24-h Holter recordings were assessed blindly in patients the day before ICD implantation or on the day of study enrolment in patients who were conservatively managed. The primary endpoint was all-cause mortality. Propensity scoring and multivariable models were used to assess the interaction between periodic repolarisation dynamics and the treatment effect of ICDs on mortality. FINDINGS: Between May 12, 2014, and Sept 7, 2018, 1371 patients were enrolled in our study. 968 of these patients underwent ICD implantation, and 403 were treated conservatively. During follow-up (median 2·7 years [IQR 2·0-3·3] in the ICD group and 1·2 years [0·8-2·7] in the control group), 138 (14%) patients died in the ICD group and 64 (16%) patients died in the control group. We noted a 43% reduction in mortality in the ICD group compared with the control group (adjusted hazard ratio [HR] 0·57 [95% CI 0·41-0·79]; p=0·0008). Periodic repolarisation dynamics significantly predicted the treatment effect of ICDs on mortality (adjusted p=0·0307). The mortality benefits associated with ICD implantation were greater in patients with periodic repolarisation dynamics of 7·5 deg or higher (n=199; adjusted HR 0·25 [95% CI 0·13-0·47] for the ICD group vs the control group; p<0·0001) than in those with periodic repolarisation dynamics less than 7·5 deg (n=1166; adjusted HR 0·69 [95% CI 0·47-1·00]; p=0·0492; pinteraction=0·0056). The number needed to treat was 18·3 (95% CI 10·6-4895·3) in patients with periodic repolarisation dynamics less than 7·5 deg and 3·1 (2·6-4·8) in those with periodic repolarisation dynamics of 7·5 deg or higher. INTERPRETATION: Periodic repolarisation dynamics predict mortality reductions associated with prophylactic implantation of ICDs in contemporarily treated patients with ischaemic or non-ischaemic cardiomyopathy. Periodic repolarisation dynamics could help to guide treatment decisions about prophylactic ICD implantation. FUNDING: The European Community's 7th Framework Programme.

Dynamic Changes of Cardiac Repolarization Instability during Exercise Testing.

INTRODUCTION: Physical exercise triggers efferent cardiac sympathetic activation. Here, we tracked the spatiotemporal properties of cardiac repolarization on a beat-to-beat basis throughout a standardized exercise test and hypothesized a detectable change at the point of the anaerobic threshold (AT). METHODS: The study included 20 healthy adults (age 35.3 ± 6.7 yr) undergoing a standardized incremental exercise test on a cycle ergometer. During exercise testing, high-resolution (2000 Hz) ECG monitoring in Frank lead configuration was performed. Three-dimensional beat-to-beat repolarization instability (dT°) was assessed by a novel vector-based method according to a previously published technology. In parallel, the lactate threshold (LT) was detected according to Dickhuth and Mader. RESULTS: We could identify a characteristic pattern of dT° signal during exercise testing. With increasing physical activity, dT° increased concordantly to heart rate. At an average of 164 ± 38 W, dT° and heart rate abruptly showed a discordant behavior, characterized by a transient drop of dT°. The maximal discordance between dT° and heart rate was defined as ATdT° and highly significantly correlated with LTDickhuth (r = 0.841, P < 0.001) and LTMader (r = 0.819, P < 0.001), which were at 156 ± 39 and 172 ± 46 W, respectively. The characteristic of dT° could not be provoked by fast atrial pacing in the absence of exercise. CONCLUSIONS: Repolarization instability shows a characteristic pattern during standardized exercise in healthy individuals that allows for a noninvasive estimation of AT.

Deceleration Capacity of Heart Rate After Acute Altitude Exposure.

Hamm, Wolfgang, Lukas von Stülpnagel, Mathias Klemm, Monika Baylacher, Konstantinos D. Rizas, Axel Bauer, and Stefan Brunner. Deceleration capacity of heart rate after acute altitude exposure. High Alt Med Biol 19:299-302, 2018. BACKGROUND: The autonomic nervous system plays a crucial role in adaptive changes after high-altitude exposure. Deceleration capacity (DC) of heart rate is an advanced marker of heart rate variability (HRV) that predominantly reflects the vagal activity of the cardiac autonomic nervous system. The impact of high-altitude exposure on DC has not been investigated yet. METHODS: In eight healthy individuals we performed a high-resolution digital 30-min electrocardiography in Frank leads configuration at baseline (521 m altitude), immediately after ascent to the Environmental Research Station Schneefernerhaus (UFS) at Zugspitze (2650 m altitude) and after a sojourn of 24 hours at this altitude. DC of heart rate was assessed using customized software. In addition, standard parameters of HRV were assessed. RESULTS: DC decreased significantly from 10.2 ± 0.8 ms to 8.9 ± 1.0 ms (p < 0.05) after acute altitude exposure. After a sojourn of 24 hours at high altitude, DC remained low at 8.6 ± 1.2 ms. There were no significant changes in standard parameters of HRV. CONCLUSION: Our findings show for the first time a decrease of DC of heart rate providing a novel insight into the dysbalance of autonomic nervous system at high altitude.