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Published in: Clinical Research in Cardiology 9/2017

01-09-2017 | Original Paper

Point-of-care testing of cardiac autonomic function for risk assessment in patients with suspected acute coronary syndromes

Authors: C. Eick, M. Duckheim, P. Groga-Bada, N. Klumpp, S. Mannes, C. S. Zuern, M. Gawaz, K. D. Rizas, Axel Bauer

Published in: Clinical Research in Cardiology | Issue 9/2017

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Abstract

Background

Impaired cardiac autonomic function has been linked to adverse outcomes in patients with acute coronary syndromes (ACS) but is not included in clinical risk models. This is the first study to investigate whether point-of-care testing of cardiac autonomic function by means of short-term deceleration capacity (DC) of heart rate improves risk assessment in patients with suspected ACS.

Methods

1821 patients with suspected ACS were prospectively enrolled if they were older than 17 years and in sinus rhythm. Short-term DC was automatically assessed from monitor recordings at hospital admission. The Global Registry of Acute Coronary Events (GRACE) score was used as gold standard risk predictor. Primary endpoint was the composite of intrahospital and 30-day mortality. Secondary endpoint was 180-day mortality.

Results

Of the 1,821 patients with suspected ACS, 28 (1.5%) and 60 (3.3%) reached the primary and secondary endpoints, respectively. DC was a highly significant predictor of both endpoints, yielding areas under the curve (AUC) of 0.784 (95% CI 0.714–0.854) and 0.781 (0.727–0.832) (p < 0.001 for both), respectively. Implementing DC into the GRACE-risk model leads to a significant increase of the C-statistics from 0.788 (0.703–0.874) to 0.825 (0.750–0.900; p < 0.01 for difference) and from 0.814 (0.759–0.864) to 0.851 (0.808–0.889; p < 0.01 for difference) for the primary and secondary endpoints, respectively. Stratification by dichotomized DC was especially powerful in patients with GRACE score <140.

Conclusions

In patients with suspected ACS, point-of-care testing of cardiac autonomic function by means of DC is feasible and improves risk assessment by the GRACE score.

Clinical Trial Registration

Clinicaltrials.gov NCT01486589.
Literature
1.
go back to reference Task Force M, Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, Bax JJ, Borger MA, Brotons C, Chew DP, Gencer B, Hasenfuss G, Kjeldsen K, Lancellotti P, Landmesser U, Mehilli J, Mukherjee D, Storey RF, Windecker S (2015) 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. doi:10.1093/eurheartj/ehv320 Task Force M, Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, Bax JJ, Borger MA, Brotons C, Chew DP, Gencer B, Hasenfuss G, Kjeldsen K, Lancellotti P, Landmesser U, Mehilli J, Mukherjee D, Storey RF, Windecker S (2015) 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. doi:10.​1093/​eurheartj/​ehv320
2.
go back to reference Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, Van De Werf F, Avezum A, Goodman SG, Flather MD, Fox KA, Global Registry of Acute Coronary Events I (2003) Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med 163(19):2345–2353. doi:10.1001/archinte.163.19.2345 CrossRefPubMed Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, Van De Werf F, Avezum A, Goodman SG, Flather MD, Fox KA, Global Registry of Acute Coronary Events I (2003) Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med 163(19):2345–2353. doi:10.​1001/​archinte.​163.​19.​2345 CrossRefPubMed
3.
go back to reference Elbarouni B, Goodman SG, Yan RT, Welsh RC, Kornder JM, Deyoung JP, Wong GC, Rose B, Grondin FR, Gallo R, Tan M, Casanova A, Eagle KA, Yan AT, Canadian Global Registry of Acute Coronary Events I (2009) Validation of the Global Registry of Acute Coronary Event (GRACE) risk score for in-hospital mortality in patients with acute coronary syndrome in Canada. Am Heart J 158(3):392–399. doi:10.1016/j.ahj.2009.06.010 Elbarouni B, Goodman SG, Yan RT, Welsh RC, Kornder JM, Deyoung JP, Wong GC, Rose B, Grondin FR, Gallo R, Tan M, Casanova A, Eagle KA, Yan AT, Canadian Global Registry of Acute Coronary Events I (2009) Validation of the Global Registry of Acute Coronary Event (GRACE) risk score for in-hospital mortality in patients with acute coronary syndrome in Canada. Am Heart J 158(3):392–399. doi:10.​1016/​j.​ahj.​2009.​06.​010
5.
go back to reference Alter DA, Venkatesh V, Chong A, Group SS (2006) Evaluating the performance of the Global Registry of Acute Coronary Events risk-adjustment index across socioeconomic strata among patients discharged from the hospital after acute myocardial infarction. Am Heart J 151(2):323–331. doi:10.1016/j.ahj.2005.07.013 CrossRefPubMed Alter DA, Venkatesh V, Chong A, Group SS (2006) Evaluating the performance of the Global Registry of Acute Coronary Events risk-adjustment index across socioeconomic strata among patients discharged from the hospital after acute myocardial infarction. Am Heart J 151(2):323–331. doi:10.​1016/​j.​ahj.​2005.​07.​013 CrossRefPubMed
6.
go back to reference Schaeffer BN, Rybczynski M, Sheikhzadeh S, Akbulak RO, Moser J, Jularic M, Schreiber D, Daubmann A, Willems S, von Kodolitsch Y, Hoffmann BA (2015) Heart rate turbulence and deceleration capacity for risk prediction of serious arrhythmic events in Marfan syndrome. Clin Res Cardiol 104(12):1054–1063. doi:10.1007/s00392-015-0873-9 CrossRefPubMed Schaeffer BN, Rybczynski M, Sheikhzadeh S, Akbulak RO, Moser J, Jularic M, Schreiber D, Daubmann A, Willems S, von Kodolitsch Y, Hoffmann BA (2015) Heart rate turbulence and deceleration capacity for risk prediction of serious arrhythmic events in Marfan syndrome. Clin Res Cardiol 104(12):1054–1063. doi:10.​1007/​s00392-015-0873-9 CrossRefPubMed
7.
go back to reference Bauer A, Barthel P, Schneider R, Ulm K, Muller A, Joeinig A, Stich R, Kiviniemi A, Hnatkova K, Huikuri H, Schomig A, Malik M, Schmidt G (2009) Improved Stratification of Autonomic Regulation for risk prediction in post-infarction patients with preserved left ventricular function (ISAR-Risk). Eur Heart J 30(5):576–583. doi:10.1093/eurheartj/ehn540 CrossRefPubMed Bauer A, Barthel P, Schneider R, Ulm K, Muller A, Joeinig A, Stich R, Kiviniemi A, Hnatkova K, Huikuri H, Schomig A, Malik M, Schmidt G (2009) Improved Stratification of Autonomic Regulation for risk prediction in post-infarction patients with preserved left ventricular function (ISAR-Risk). Eur Heart J 30(5):576–583. doi:10.​1093/​eurheartj/​ehn540 CrossRefPubMed
8.
go back to reference Bauer A, Kantelhardt JW, Bunde A, Barthel P, Schneider R, Malik M, Schmidt G (2006) Phase-rectified signal averaging detects quasi-periodicities in non-stationary data. Physica A 364:423–434CrossRef Bauer A, Kantelhardt JW, Bunde A, Barthel P, Schneider R, Malik M, Schmidt G (2006) Phase-rectified signal averaging detects quasi-periodicities in non-stationary data. Physica A 364:423–434CrossRef
9.
go back to reference Bauer A, Kantelhardt JW, Barthel P, Schneider R, Makikallio T, Ulm K, Hnatkova K, Schomig A, Huikuri H, Bunde A, Malik M, Schmidt G (2006) Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: cohort study. Lancet 367(9523):1674–1681CrossRefPubMed Bauer A, Kantelhardt JW, Barthel P, Schneider R, Makikallio T, Ulm K, Hnatkova K, Schomig A, Huikuri H, Bunde A, Malik M, Schmidt G (2006) Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: cohort study. Lancet 367(9523):1674–1681CrossRefPubMed
11.
go back to reference Schwartz PJ, La Rovere MT, Vanoli E (1992) Autonomic nervous system and sudden cardiac death. Experimental basis and clinical observations for post-myocardial infarction risk stratification. Circulation 85(1 Suppl):I77–I91PubMed Schwartz PJ, La Rovere MT, Vanoli E (1992) Autonomic nervous system and sudden cardiac death. Experimental basis and clinical observations for post-myocardial infarction risk stratification. Circulation 85(1 Suppl):I77–I91PubMed
12.
go back to reference Eick C, Rizas KD, Zuern CS, Bauer A (2014) Automated assessment of cardiac autonomic function by means of deceleration capacity from noisy, nonstationary ECG signals: validation study. Ann Noninvasive Electrocardiol 19(2):122–128. doi:10.1111/anec.12107 CrossRefPubMed Eick C, Rizas KD, Zuern CS, Bauer A (2014) Automated assessment of cardiac autonomic function by means of deceleration capacity from noisy, nonstationary ECG signals: validation study. Ann Noninvasive Electrocardiol 19(2):122–128. doi:10.​1111/​anec.​12107 CrossRefPubMed
13.
go back to reference Eick C, Rizas KD, Meyer-Zurn CS, Groga-Bada P, Hamm W, Kreth F, Overkamp D, Weyrich P, Gawaz M, Bauer A (2015) Autonomic nervous system activity as risk predictor in the medical emergency department: a prospective cohort study. Crit Care Med 43(5):1079–1086. doi:10.1097/CCM.0000000000000922 CrossRefPubMed Eick C, Rizas KD, Meyer-Zurn CS, Groga-Bada P, Hamm W, Kreth F, Overkamp D, Weyrich P, Gawaz M, Bauer A (2015) Autonomic nervous system activity as risk predictor in the medical emergency department: a prospective cohort study. Crit Care Med 43(5):1079–1086. doi:10.​1097/​CCM.​0000000000000922​ CrossRefPubMed
15.
go back to reference Bauer A, Kantelhardt JW, Bunde A, Malik M, Schneider R, Schmidt G (2006) Phase-rectified signal averaging detects quasi-periodicities in non-stationary data. Physica A 364:423–434CrossRef Bauer A, Kantelhardt JW, Bunde A, Malik M, Schneider R, Schmidt G (2006) Phase-rectified signal averaging detects quasi-periodicities in non-stationary data. Physica A 364:423–434CrossRef
16.
go back to reference Eick C, Rizas KD, Zuern CS, Bauer A (2013) Automated assessment of cardiac autonomic function by means of deceleration capacity from noisy, nonstationary ECG signals: validation study. Ann Noninvasive Electrocardiol. doi:10.1111/anec.12107 PubMed Eick C, Rizas KD, Zuern CS, Bauer A (2013) Automated assessment of cardiac autonomic function by means of deceleration capacity from noisy, nonstationary ECG signals: validation study. Ann Noninvasive Electrocardiol. doi:10.​1111/​anec.​12107 PubMed
17.
go back to reference Kleiger RE, Miller JP, Krone RJ, Bigger JT Jr (1990) The independence of cycle length variability and exercise testing on predicting mortality of patients surviving acute myocardial infarction. The Multicenter Postinfarction Research Group. Am J Cardiol 65(7):408–411CrossRefPubMed Kleiger RE, Miller JP, Krone RJ, Bigger JT Jr (1990) The independence of cycle length variability and exercise testing on predicting mortality of patients surviving acute myocardial infarction. The Multicenter Postinfarction Research Group. Am J Cardiol 65(7):408–411CrossRefPubMed
18.
go back to reference La Rovere MT, Bigger JT Jr, Marcus FI, Mortara A, Schwartz PJ (1998) Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet 351(9101):478–484CrossRefPubMed La Rovere MT, Bigger JT Jr, Marcus FI, Mortara A, Schwartz PJ (1998) Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet 351(9101):478–484CrossRefPubMed
19.
go back to reference Schroeder J, Hamada S, Grundlinger N, Rubeau T, Altiok E, Ulbrich K, Keszei A, Marx N, Becker M (2016) Myocardial deformation by strain echocardiography identifies patients with acute coronary syndrome and non-diagnostic ECG presenting in a chest pain unit: a prospective study of diagnostic accuracy. Clin Res Cardiol 105(3):248–256. doi:10.1007/s00392-015-0916-2 CrossRefPubMed Schroeder J, Hamada S, Grundlinger N, Rubeau T, Altiok E, Ulbrich K, Keszei A, Marx N, Becker M (2016) Myocardial deformation by strain echocardiography identifies patients with acute coronary syndrome and non-diagnostic ECG presenting in a chest pain unit: a prospective study of diagnostic accuracy. Clin Res Cardiol 105(3):248–256. doi:10.​1007/​s00392-015-0916-2 CrossRefPubMed
20.
go back to reference Hillinger P, Twerenbold R, Wildi K, Rubini Gimenez M, Jaeger C, Boeddinghaus J, Nestelberger T, Grimm K, Reichlin T, Stallone F, Puelacher C, Sabti Z, Kozhuharov N, Honegger U, Ballarino P, Miro O, Denhaerynck K, Ekrem T, Kohler C, Bingisser R, Osswald S, Mueller C (2017) Gender-specific uncertainties in the diagnosis of acute coronary syndrome. Clin Res Cardiol 106(1):28–37. doi:10.1007/s00392-016-1020-y CrossRefPubMed Hillinger P, Twerenbold R, Wildi K, Rubini Gimenez M, Jaeger C, Boeddinghaus J, Nestelberger T, Grimm K, Reichlin T, Stallone F, Puelacher C, Sabti Z, Kozhuharov N, Honegger U, Ballarino P, Miro O, Denhaerynck K, Ekrem T, Kohler C, Bingisser R, Osswald S, Mueller C (2017) Gender-specific uncertainties in the diagnosis of acute coronary syndrome. Clin Res Cardiol 106(1):28–37. doi:10.​1007/​s00392-016-1020-y CrossRefPubMed
21.
go back to reference Davis M, Diamond J, Montgomery D, Krishnan S, Eagle K, Jackson E (2015) Acute coronary syndrome in young women under 55 years of age: clinical characteristics, treatment, and outcomes. Clin Res Cardiol 104(8):648–655. doi:10.1007/s00392-015-0827-2 CrossRefPubMed Davis M, Diamond J, Montgomery D, Krishnan S, Eagle K, Jackson E (2015) Acute coronary syndrome in young women under 55 years of age: clinical characteristics, treatment, and outcomes. Clin Res Cardiol 104(8):648–655. doi:10.​1007/​s00392-015-0827-2 CrossRefPubMed
22.
go back to reference Bonnemeier H, Hartmann F, Wiegand UK, Irmer C, Kurz T, Tolg R, Katus HA, Richardt G (2000) Heart rate variability in patients with acute myocardial infarction undergoing primary coronary angioplasty. Am J Cardiol 85(7):815–820CrossRefPubMed Bonnemeier H, Hartmann F, Wiegand UK, Irmer C, Kurz T, Tolg R, Katus HA, Richardt G (2000) Heart rate variability in patients with acute myocardial infarction undergoing primary coronary angioplasty. Am J Cardiol 85(7):815–820CrossRefPubMed
23.
go back to reference Bonnemeier H, Wiegand UK, Friedlbinder J, Schulenburg S, Hartmann F, Bode F, Katus HA, Richardt G (2003) Reflex cardiac activity in ischemia and reperfusion: heart rate turbulence in patients undergoing direct percutaneous coronary intervention for acute myocardial infarction. Circulation 108(8):958–964. doi:10.1161/01.CIR.0000085072.19047.D8 CrossRefPubMed Bonnemeier H, Wiegand UK, Friedlbinder J, Schulenburg S, Hartmann F, Bode F, Katus HA, Richardt G (2003) Reflex cardiac activity in ischemia and reperfusion: heart rate turbulence in patients undergoing direct percutaneous coronary intervention for acute myocardial infarction. Circulation 108(8):958–964. doi:10.​1161/​01.​CIR.​0000085072.​19047.​D8 CrossRefPubMed
24.
go back to reference Sade E, Aytemir K, Oto A, Nazli N, Ozmen F, Ozkutlu H, Tokgozoglu L, Aksoyek S, Ovunc K, Kabakci G, Ozer N, Kes S (2003) Assessment of heart rate turbulence in the acute phase of myocardial infarction for long-term prognosis. Pacing and clinical electrophysiology. PACE 26(2 Pt 1):544–550CrossRefPubMed Sade E, Aytemir K, Oto A, Nazli N, Ozmen F, Ozkutlu H, Tokgozoglu L, Aksoyek S, Ovunc K, Kabakci G, Ozer N, Kes S (2003) Assessment of heart rate turbulence in the acute phase of myocardial infarction for long-term prognosis. Pacing and clinical electrophysiology. PACE 26(2 Pt 1):544–550CrossRefPubMed
25.
go back to reference Fox KA, Dabbous OH, Goldberg RJ, Pieper KS, Eagle KA, Van de Werf F, Avezum A, Goodman SG, Flather MD, Anderson FA Jr, Granger CB (2006) Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE). Bmj 333(7578):1091. doi:10.1136/bmj.38985.646481.55 CrossRefPubMedPubMedCentral Fox KA, Dabbous OH, Goldberg RJ, Pieper KS, Eagle KA, Van de Werf F, Avezum A, Goodman SG, Flather MD, Anderson FA Jr, Granger CB (2006) Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE). Bmj 333(7578):1091. doi:10.​1136/​bmj.​38985.​646481.​55 CrossRefPubMedPubMedCentral
26.
go back to reference Amsterdam EA, Wenger NK, Brindis RG, Casey DE, Jr., Ganiats TG, Holmes DR, Jr., Jaffe AS, Jneid H, Kelly RF, Kontos MC, Levine GN, Liebson PR, Mukherjee D, Peterson ED, Sabatine MS, Smalling RW, Zieman SJ, Members AATF, Society for Cardiovascular A, Interventions, the Society of Thoracic S (2014) 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 130(25):2354–2394. doi:10.1161/CIR.0000000000000133 CrossRef Amsterdam EA, Wenger NK, Brindis RG, Casey DE, Jr., Ganiats TG, Holmes DR, Jr., Jaffe AS, Jneid H, Kelly RF, Kontos MC, Levine GN, Liebson PR, Mukherjee D, Peterson ED, Sabatine MS, Smalling RW, Zieman SJ, Members AATF, Society for Cardiovascular A, Interventions, the Society of Thoracic S (2014) 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 130(25):2354–2394. doi:10.​1161/​CIR.​0000000000000133​ CrossRef
27.
go back to reference Steg PG, Goldberg RJ, Gore JM, Fox KA, Eagle KA, Flather MD, Sadiq I, Kasper R, Rushton-Mellor SK, Anderson FA, Investigators G (2002) Baseline characteristics, management practices, and in-hospital outcomes of patients hospitalized with acute coronary syndromes in the Global Registry of Acute Coronary Events (GRACE). Am J Cardiol 90(4):358–363CrossRefPubMed Steg PG, Goldberg RJ, Gore JM, Fox KA, Eagle KA, Flather MD, Sadiq I, Kasper R, Rushton-Mellor SK, Anderson FA, Investigators G (2002) Baseline characteristics, management practices, and in-hospital outcomes of patients hospitalized with acute coronary syndromes in the Global Registry of Acute Coronary Events (GRACE). Am J Cardiol 90(4):358–363CrossRefPubMed
28.
go back to reference Pedersen OD, Abildstrom SZ, Ottesen MM, Rask-Madsen C, Bagger H, Kober L, Torp-Pedersen C, Investigators TS (2006) Increased risk of sudden and non-sudden cardiovascular death in patients with atrial fibrillation/flutter following acute myocardial infarction. Eur Heart J 27(3):290–295. doi:10.1093/eurheartj/ehi629 CrossRefPubMed Pedersen OD, Abildstrom SZ, Ottesen MM, Rask-Madsen C, Bagger H, Kober L, Torp-Pedersen C, Investigators TS (2006) Increased risk of sudden and non-sudden cardiovascular death in patients with atrial fibrillation/flutter following acute myocardial infarction. Eur Heart J 27(3):290–295. doi:10.​1093/​eurheartj/​ehi629 CrossRefPubMed
Metadata
Title
Point-of-care testing of cardiac autonomic function for risk assessment in patients with suspected acute coronary syndromes
Authors
C. Eick
M. Duckheim
P. Groga-Bada
N. Klumpp
S. Mannes
C. S. Zuern
M. Gawaz
K. D. Rizas
Axel Bauer
Publication date
01-09-2017
Publisher
Springer Berlin Heidelberg
Published in
Clinical Research in Cardiology / Issue 9/2017
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-017-1104-3

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