Skip to main content
Erschienen in: Pediatric Cardiology 1/2015

01.01.2015 | Original Article

Short-Term Heart Rate Variability in a Population-Based Sample of 10-Year-Old Children

verfasst von: Denise C. Jarrin, Jennifer J. McGrath, Paul Poirier, Louise Séguin, Richard E. Tremblay, Jacques Y. Montplaisir, Gilles Paradis, Jean R. Séguin

Erschienen in: Pediatric Cardiology | Ausgabe 1/2015

Einloggen, um Zugang zu erhalten

Abstract

Heart rate variability (HRV) is a non-invasive quantitative marker of cardiac autonomic function derived from continuous electrocardiogram (ECG) recordings. Normative HRV values and development factors have not been established in pediatric populations. The objective was to derive referent time- and frequency-domain HRV values for a population-based sample of children. Children aged 9–11 years (N = 1,036) participated in the Québec Longitudinal Study of Child Development cohort cardiovascular health screening. Registered nurses measured anthropometrics (height, weight) and children wore an ambulatory Holter monitor to continuously record an ECG signal. HRV variables included time (SDNN, pNN50, RMSSD, SDANN) and frequency (HF, LF, LF/HF ratio) domain variables. Normative HRV values, stratified by age, sex, and heart rate, are presented. Greater heart rate (β avg  = −0.60, R avg 2  = 0.39), pubertal maturation (β avg = −0.11, R avg 2  = 0.01), later ECG recording times (β avg = −0.19, R avg 2  = 0.07), and higher diastolic blood pressure (β avg = −0.11, R avg 2  = 0.01) were significantly associated with reduced HRV in 10-year-old children. The normative HRV values permit clinicians to monitor, describe, and establish pediatric nosologies in primary care and research settings, which may improve treatment of diseases associated with HRV in children. By better understanding existing values, the practical applicability of HRV among clinicians will be enhanced. Lastly, developmental (e.g., puberty) and procedural (e.g., recording time) factors were identified that will improve recording procedures and interpretation of results.
Literatur
1.
Zurück zum Zitat Berntson GG, Cacioppo JT, Quigley KS (1993) Cardiac psychophysiology and autonomic space in humans: empirical perspectives and conceptual implications. Psychol Bull 114:293–322CrossRef Berntson GG, Cacioppo JT, Quigley KS (1993) Cardiac psychophysiology and autonomic space in humans: empirical perspectives and conceptual implications. Psychol Bull 114:293–322CrossRef
2.
Zurück zum Zitat Berntson GG, Bigger JT, Eckberg DL, Grossman P, Kaufmann PG, Malik M et al (1997) Heart rate variability: origins, methods, and interpretive caveats. Psychophysiology 34(6):623–648PubMedCrossRef Berntson GG, Bigger JT, Eckberg DL, Grossman P, Kaufmann PG, Malik M et al (1997) Heart rate variability: origins, methods, and interpretive caveats. Psychophysiology 34(6):623–648PubMedCrossRef
3.
Zurück zum Zitat Białłkowski J, Karwot B, Szkutnik M, Sredniawa B et al (2003) Comparison of heart rate variability between surgical and interventional closure of atrial septal defect in children. Am J Cardiol 92:356–358CrossRef Białłkowski J, Karwot B, Szkutnik M, Sredniawa B et al (2003) Comparison of heart rate variability between surgical and interventional closure of atrial septal defect in children. Am J Cardiol 92:356–358CrossRef
4.
Zurück zum Zitat Blom EH, Olsson EMG, Serlachius E, Ericson M, Ingvar M (2009) Heart rate variability is related to self-reported physical activity in a healthy adolescent population. Europ J Appl Physiol 106(6):877–883CrossRef Blom EH, Olsson EMG, Serlachius E, Ericson M, Ingvar M (2009) Heart rate variability is related to self-reported physical activity in a healthy adolescent population. Europ J Appl Physiol 106(6):877–883CrossRef
5.
Zurück zum Zitat Chen S-R, Chiu H-W, Lee Y-J, Sheen T-C, Jeng C (2012) Impact of pubertal development and physical activity on heart rate variability in overweight and obese children in Taiwan. J Sch Nurs 4:284–290CrossRef Chen S-R, Chiu H-W, Lee Y-J, Sheen T-C, Jeng C (2012) Impact of pubertal development and physical activity on heart rate variability in overweight and obese children in Taiwan. J Sch Nurs 4:284–290CrossRef
6.
Zurück zum Zitat Faulkner MS, Hathaway D, Tolley B (2003) Cardiovascular autonomic function in healthy adolescents. Heart Lung 32:10–22PubMedCrossRef Faulkner MS, Hathaway D, Tolley B (2003) Cardiovascular autonomic function in healthy adolescents. Heart Lung 32:10–22PubMedCrossRef
7.
Zurück zum Zitat Finley J, Nugent ST (1995) Heart rate variability in infants, children and young adults. J Auto Nerv 51:103–108CrossRef Finley J, Nugent ST (1995) Heart rate variability in infants, children and young adults. J Auto Nerv 51:103–108CrossRef
8.
Zurück zum Zitat Finley JP, Nugent ST, Hellenbrand W (1987) Heart-rate variability in children. Spectral analysis of developmental changes between 5 and 24 years. Can J Physiol Pharmacol 65(10):2048–2052PubMedCrossRef Finley JP, Nugent ST, Hellenbrand W (1987) Heart-rate variability in children. Spectral analysis of developmental changes between 5 and 24 years. Can J Physiol Pharmacol 65(10):2048–2052PubMedCrossRef
9.
Zurück zum Zitat Fleming S, Thompson M, Stevens R, Heneghan C, Plüddemann A, Maconochie I et al (2011) Normal ranges of heart rate and respiratory rate in children from birth to 18 years of age: a systematic review of observational studies. Lancet 377:1011–1018PubMedCentralPubMedCrossRef Fleming S, Thompson M, Stevens R, Heneghan C, Plüddemann A, Maconochie I et al (2011) Normal ranges of heart rate and respiratory rate in children from birth to 18 years of age: a systematic review of observational studies. Lancet 377:1011–1018PubMedCentralPubMedCrossRef
10.
Zurück zum Zitat Fujiwara J, Kimura S, Tsukayama H, Nakahara S, Haibara S et al (2004) Evaluation of the autonomic nervous system function in children with primary monosymptomatic nocturnal enuresis-power spectrum. Scand J Urol Nephrol 35:350–356CrossRef Fujiwara J, Kimura S, Tsukayama H, Nakahara S, Haibara S et al (2004) Evaluation of the autonomic nervous system function in children with primary monosymptomatic nocturnal enuresis-power spectrum. Scand J Urol Nephrol 35:350–356CrossRef
11.
Zurück zum Zitat Golding J, Pembrey M, Jones R, The Alspac Study Team (2001) ALSPAC–the avon longitudinal study of parents and children. Paed Perin Epidemiol 15:74–87CrossRef Golding J, Pembrey M, Jones R, The Alspac Study Team (2001) ALSPAC–the avon longitudinal study of parents and children. Paed Perin Epidemiol 15:74–87CrossRef
12.
Zurück zum Zitat Guo YF, Stein PK (2003) Circadian rhythm in the cardiovascular system. Am Heart J 145:779–786PubMedCrossRef Guo YF, Stein PK (2003) Circadian rhythm in the cardiovascular system. Am Heart J 145:779–786PubMedCrossRef
13.
Zurück zum Zitat Hon EH, Lee ST (1965) Electronic evaluations of the fetal heart rate patterns preceding fetal death, further observations. Am J Obstet Gynae 87:814–826 Hon EH, Lee ST (1965) Electronic evaluations of the fetal heart rate patterns preceding fetal death, further observations. Am J Obstet Gynae 87:814–826
14.
Zurück zum Zitat Jetté M (2002) Survey description and methodology: Part I. Logistics and longitudinal data collections. Quebec Longitudinal Study of Child Development (QLSCD 1998–2000, Vol. 2, No. 1). Institut de la Statistique du Quebec, Quebec Jetté M (2002) Survey description and methodology: Part I. Logistics and longitudinal data collections. Quebec Longitudinal Study of Child Development (QLSCD 1998–2000, Vol. 2, No. 1). Institut de la Statistique du Quebec, Quebec
15.
Zurück zum Zitat Katheria A, Rich W, Finer N (2012) Electrocardiogram provides a continuous heart rate faster than oximetry during neonatal resuscitation. Pediatrics 130:1177–1181CrossRef Katheria A, Rich W, Finer N (2012) Electrocardiogram provides a continuous heart rate faster than oximetry during neonatal resuscitation. Pediatrics 130:1177–1181CrossRef
16.
Zurück zum Zitat Kaufman CL, Kaiser DR, Steinberger J, Dengel DR (2007) Relationships between heart rate variability, vascular function, and adiposity in children. Clin Auton Res 17(3):165–171PubMedCrossRef Kaufman CL, Kaiser DR, Steinberger J, Dengel DR (2007) Relationships between heart rate variability, vascular function, and adiposity in children. Clin Auton Res 17(3):165–171PubMedCrossRef
17.
Zurück zum Zitat Kleiger RE, Miller JP, Bigger JT, Moss AR (1987) Multicenter post-infarction research group: decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 59:256–262PubMedCrossRef Kleiger RE, Miller JP, Bigger JT, Moss AR (1987) Multicenter post-infarction research group: decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 59:256–262PubMedCrossRef
18.
Zurück zum Zitat Kwok K-L, Yung T-C, Ng DK, Chan C-H, Lau W-F, Fu Y-M (2011) Heart rate variability in childhood obstructive sleep apnea. Ped Pulmonol 210:205–210CrossRef Kwok K-L, Yung T-C, Ng DK, Chan C-H, Lau W-F, Fu Y-M (2011) Heart rate variability in childhood obstructive sleep apnea. Ped Pulmonol 210:205–210CrossRef
19.
Zurück zum Zitat Lenard Z, Studinger P, Mersich B, Kocsis L, Kollai M (2004) Maturation of cardiovagal autonomic function from childhood to young adult age. Circulation 110(16):2307–2312PubMedCrossRef Lenard Z, Studinger P, Mersich B, Kocsis L, Kollai M (2004) Maturation of cardiovagal autonomic function from childhood to young adult age. Circulation 110(16):2307–2312PubMedCrossRef
20.
Zurück zum Zitat Liao D, Li X, Rodriguez-Colon SM, Liu J, Vgontzas AN, Calhoun S, Bixler EO (2010) Sleep-disordered breathing and cardiac autonomic modulation in children. Sleep Med 11(5):484–848PubMedCentralPubMedCrossRef Liao D, Li X, Rodriguez-Colon SM, Liu J, Vgontzas AN, Calhoun S, Bixler EO (2010) Sleep-disordered breathing and cardiac autonomic modulation in children. Sleep Med 11(5):484–848PubMedCentralPubMedCrossRef
21.
Zurück zum Zitat Malpas S, Purdie GL (1990) Circadian variation of heart rate variability. Cardiovasc Res 24:210–213PubMedCrossRef Malpas S, Purdie GL (1990) Circadian variation of heart rate variability. Cardiovasc Res 24:210–213PubMedCrossRef
22.
Zurück zum Zitat Martini G, Riva P, Rabbia F, Molini V, Ferrero GB, Cerutti F, Carra R et al (2001) Heart rate variability in childhood obesity. Clin Auton Res 11(2):87–91PubMedCrossRef Martini G, Riva P, Rabbia F, Molini V, Ferrero GB, Cerutti F, Carra R et al (2001) Heart rate variability in childhood obesity. Clin Auton Res 11(2):87–91PubMedCrossRef
23.
Zurück zum Zitat Massin M, von Bernuth G (1997) Normal ranges of heart rate variability during infancy and childhood. Ped Cardiol 18:297–302CrossRef Massin M, von Bernuth G (1997) Normal ranges of heart rate variability during infancy and childhood. Ped Cardiol 18:297–302CrossRef
24.
25.
Zurück zum Zitat Morris NM, Udry JR (1980) Validation of a self-administered instrument to assess stage of adolescent development. J Youth Adolesc 9:271–280PubMedCrossRef Morris NM, Udry JR (1980) Validation of a self-administered instrument to assess stage of adolescent development. J Youth Adolesc 9:271–280PubMedCrossRef
26.
Zurück zum Zitat Nagai N, Matsumoto T, Kita H, Moritani T (2003) Autonomic nervous system activity and the state and development of obesity in Japanese school children. Obes Res 11(1):25–32PubMedCrossRef Nagai N, Matsumoto T, Kita H, Moritani T (2003) Autonomic nervous system activity and the state and development of obesity in Japanese school children. Obes Res 11(1):25–32PubMedCrossRef
27.
Zurück zum Zitat Netherton C, Goodyer I, Tamplin A, Herbert J (2004) Salivary cortisol and dehydroepiandrosterone in relation to puberty and gender. Psychoneuroendocrinology 29:125–140PubMedCrossRef Netherton C, Goodyer I, Tamplin A, Herbert J (2004) Salivary cortisol and dehydroepiandrosterone in relation to puberty and gender. Psychoneuroendocrinology 29:125–140PubMedCrossRef
28.
Zurück zum Zitat Ogden CL, Kuczmarski RJ, Flegal KM, Mei Z, Guo S, Wei R et al (2002) Growth charts for the United States: improvements to the 1977 National Center for Health Statistics Version. Pediatrics 109:45–60PubMedCrossRef Ogden CL, Kuczmarski RJ, Flegal KM, Mei Z, Guo S, Wei R et al (2002) Growth charts for the United States: improvements to the 1977 National Center for Health Statistics Version. Pediatrics 109:45–60PubMedCrossRef
30.
Zurück zum Zitat Palatini P, Julius S (2009) The role of cardiac autonomic function in hypertension and cardiovascular disease. Curr Hypertens Rep 11:199–205PubMedCrossRef Palatini P, Julius S (2009) The role of cardiac autonomic function in hypertension and cardiovascular disease. Curr Hypertens Rep 11:199–205PubMedCrossRef
31.
Zurück zum Zitat Reed KE, Warburton DER, Whitney CL, McKay HA (2006) Differences in heart rate variability between Asian and Caucasian children living in the same Canadian community. Appl Physiol Nutr Metab 31:277–282PubMedCrossRef Reed KE, Warburton DER, Whitney CL, McKay HA (2006) Differences in heart rate variability between Asian and Caucasian children living in the same Canadian community. Appl Physiol Nutr Metab 31:277–282PubMedCrossRef
32.
Zurück zum Zitat Rodríguez-colón SM, He F, Shaffer ML, Li X, Vgontzas AN, Bixler EO et al (2011) Insomnia symptoms and sleep duration are associated with impaired cardiac autonomic modulation in children. Neurosci Med. 2:288–294CrossRef Rodríguez-colón SM, He F, Shaffer ML, Li X, Vgontzas AN, Bixler EO et al (2011) Insomnia symptoms and sleep duration are associated with impaired cardiac autonomic modulation in children. Neurosci Med. 2:288–294CrossRef
33.
Zurück zum Zitat Rodríguez-Colón SM, Bixler EO, Li X, Vgontzas AN, Liao D (2011) Obesity is associated with impaired cardiac autonomic modulation in children. IJPO 6(2):128–134PubMedCentralPubMed Rodríguez-Colón SM, Bixler EO, Li X, Vgontzas AN, Liao D (2011) Obesity is associated with impaired cardiac autonomic modulation in children. IJPO 6(2):128–134PubMedCentralPubMed
34.
Zurück zum Zitat Rogol AD, Clark PA, Roemmich JN (2000) Growth and pubertal development in children and adolescents: effects of diet and physical activity. Am J Clin Nutr 72:521s–528sPubMed Rogol AD, Clark PA, Roemmich JN (2000) Growth and pubertal development in children and adolescents: effects of diet and physical activity. Am J Clin Nutr 72:521s–528sPubMed
35.
Zurück zum Zitat Rydberg A, Rask P, Hörnsten R, Teien D (2004) Heart rate variability in children with Fontan circulation. Ped Cardiol 25(4):365–369CrossRef Rydberg A, Rask P, Hörnsten R, Teien D (2004) Heart rate variability in children with Fontan circulation. Ped Cardiol 25(4):365–369CrossRef
36.
Zurück zum Zitat Schroeder EB, Duanping L, Chambless LE, Prineas RJ, Evans GW, Heiss G (2003) Hypertension, blood pressure, and heart rate variability. The atherosclerosis risk in communities (ARIC) study. Hypertension 42:1106–1111PubMedCrossRef Schroeder EB, Duanping L, Chambless LE, Prineas RJ, Evans GW, Heiss G (2003) Hypertension, blood pressure, and heart rate variability. The atherosclerosis risk in communities (ARIC) study. Hypertension 42:1106–1111PubMedCrossRef
37.
Zurück zum Zitat Silvetti MS, Drago F, Ragonese P (2001) Heart rate variability in healthy children and adolescents is partially related to age and gender. Int J Cardiol 81:169–174PubMedCrossRef Silvetti MS, Drago F, Ragonese P (2001) Heart rate variability in healthy children and adolescents is partially related to age and gender. Int J Cardiol 81:169–174PubMedCrossRef
38.
Zurück zum Zitat Stein PK, Kleiger RE, Rottman JN (1997) Differing effects of age on heart rate variability in men and women. Am J Cardiol 80:302–305PubMedCrossRef Stein PK, Kleiger RE, Rottman JN (1997) Differing effects of age on heart rate variability in men and women. Am J Cardiol 80:302–305PubMedCrossRef
39.
Zurück zum Zitat Task Force of the European Society of Cardiology (1996) Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation 93:1043–1065CrossRef Task Force of the European Society of Cardiology (1996) Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation 93:1043–1065CrossRef
40.
Zurück zum Zitat Thayer JF, Sternberg E (2006) Beyond heart rate variability: vagal regulation of allostatic systems. Ann N Y Acad Sci 1088:361–372PubMedCrossRef Thayer JF, Sternberg E (2006) Beyond heart rate variability: vagal regulation of allostatic systems. Ann N Y Acad Sci 1088:361–372PubMedCrossRef
41.
Zurück zum Zitat Tremaine RB, Dorrian J, Blunden S (2010) Measuring sleep habits using the sleep timing questionnaire: a validation study for school-age children. Sleep Biol Rhythms 8:194–202CrossRef Tremaine RB, Dorrian J, Blunden S (2010) Measuring sleep habits using the sleep timing questionnaire: a validation study for school-age children. Sleep Biol Rhythms 8:194–202CrossRef
42.
Zurück zum Zitat Tsuji H, Venditti FJ, Manders ES, Evans JC, Larson MG, Feldman CL et al (1996) Determinants of heart rate variability. J Am Coll Cardiol 28:1539–1546PubMedCrossRef Tsuji H, Venditti FJ, Manders ES, Evans JC, Larson MG, Feldman CL et al (1996) Determinants of heart rate variability. J Am Coll Cardiol 28:1539–1546PubMedCrossRef
43.
Zurück zum Zitat Umetani K, Singer DH, McCraty R, Atkinson M (1998) Twenty-four hour time domain heart rate variability and heart rate: relations to age and gender over nine decades. J Am Col Card 31(3):593–601CrossRef Umetani K, Singer DH, McCraty R, Atkinson M (1998) Twenty-four hour time domain heart rate variability and heart rate: relations to age and gender over nine decades. J Am Col Card 31(3):593–601CrossRef
44.
Zurück zum Zitat Wallis LA, Healy M, Undy MB, Maconochie I (2005) Age related reference ranges for respiration rate and heart rate from 4 to 16 years. Arch Dis Child 90:1117–1121PubMedCentralPubMedCrossRef Wallis LA, Healy M, Undy MB, Maconochie I (2005) Age related reference ranges for respiration rate and heart rate from 4 to 16 years. Arch Dis Child 90:1117–1121PubMedCentralPubMedCrossRef
45.
Zurück zum Zitat Wang X, Thayer JF, Treiber F, Snieder H (2005) Ethnic differences and heritability of heart rate variability in African- and European American youth. Am J Cardiol 96:1166–1172PubMedCrossRef Wang X, Thayer JF, Treiber F, Snieder H (2005) Ethnic differences and heritability of heart rate variability in African- and European American youth. Am J Cardiol 96:1166–1172PubMedCrossRef
46.
Zurück zum Zitat Wawryk AM, Bates DJ, Couper JJ (1997) Power spectral analysis of heart rate variability in children and adolescents with IDDM. Diabetes Care 20:1416–1421PubMedCrossRef Wawryk AM, Bates DJ, Couper JJ (1997) Power spectral analysis of heart rate variability in children and adolescents with IDDM. Diabetes Care 20:1416–1421PubMedCrossRef
47.
Zurück zum Zitat Webber LS, Osganian V, Luepker RV, Feldman HA, Stone EJ et al (1995) Cardiovascular risk factors among 3rd grade children in four regions of United States: the CATCH study. Am J Epidemiol 141:428–439PubMed Webber LS, Osganian V, Luepker RV, Feldman HA, Stone EJ et al (1995) Cardiovascular risk factors among 3rd grade children in four regions of United States: the CATCH study. Am J Epidemiol 141:428–439PubMed
48.
Zurück zum Zitat Winsley RJ, Armstrong N, Bywater K, Fawkner SG (2003) Reliability of heart rate variability measures at rest and during light exercise in children. Brit J Sports Med 37(6):550–552CrossRef Winsley RJ, Armstrong N, Bywater K, Fawkner SG (2003) Reliability of heart rate variability measures at rest and during light exercise in children. Brit J Sports Med 37(6):550–552CrossRef
49.
Zurück zum Zitat Wolfson AR, Carskadon MA (1998) Sleep schedules and daytime functioning in adolescents. Child Dev 69:875–887PubMedCrossRef Wolfson AR, Carskadon MA (1998) Sleep schedules and daytime functioning in adolescents. Child Dev 69:875–887PubMedCrossRef
50.
Zurück zum Zitat Yamasaki Y, Kodama M, Matsuhisa M (1996) Diurnal heart rate variability in healthy subjects: effects of aging and sex differences. Am J Physiol 271:303–310 Yamasaki Y, Kodama M, Matsuhisa M (1996) Diurnal heart rate variability in healthy subjects: effects of aging and sex differences. Am J Physiol 271:303–310
Metadaten
Titel
Short-Term Heart Rate Variability in a Population-Based Sample of 10-Year-Old Children
verfasst von
Denise C. Jarrin
Jennifer J. McGrath
Paul Poirier
Louise Séguin
Richard E. Tremblay
Jacques Y. Montplaisir
Gilles Paradis
Jean R. Séguin
Publikationsdatum
01.01.2015
Verlag
Springer US
Erschienen in
Pediatric Cardiology / Ausgabe 1/2015
Print ISSN: 0172-0643
Elektronische ISSN: 1432-1971
DOI
https://doi.org/10.1007/s00246-014-0962-y

Weitere Artikel der Ausgabe 1/2015

Pediatric Cardiology 1/2015 Zur Ausgabe

Screening-Mammografie offenbart erhöhtes Herz-Kreislauf-Risiko

26.04.2024 Mammografie Nachrichten

Routinemäßige Mammografien helfen, Brustkrebs frühzeitig zu erkennen. Anhand der Röntgenuntersuchung lassen sich aber auch kardiovaskuläre Risikopatientinnen identifizieren. Als zuverlässiger Anhaltspunkt gilt die Verkalkung der Brustarterien.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Adipositas-Medikament auch gegen Schlafapnoe wirksam

24.04.2024 Adipositas Nachrichten

Der als Antidiabetikum sowie zum Gewichtsmanagement zugelassene Wirkstoff Tirzepatid hat in Studien bei adipösen Patienten auch schlafbezogene Atmungsstörungen deutlich reduziert, informiert der Hersteller in einer Vorab-Meldung zum Studienausgang.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.