The History and Future of Beta Blockers in Heart Failure Treatment in Children and Adults
Main Article Content
Abstract
Abstract
Today, in adult cardiology, the efficacy of beta blockers in patients with congestive heart failure is well established. Beta blockers, as a drug class, provide mortality benefits in comparison with placebo, or standard treatment, in patients with mild to severe heart failure. However, 40 years after Waagstein's first reports in adults and 20 years after our reports in infants with congenital heart defects, beta blockers are still a long way from routine clinical use in pediatric heart failure. Pediatric Cardiology has missed this milestone in heart failure treatment because the necessary clinical studies have not been carried out. However, other pediatricians were more attentive. After using propranolol in infants with a cardiomyopathy due to hemangiomatosis, several new specific pediatric indications for propranolol were unveiled and all appear to be related to its vascular effects: Hemangioma - Lymphatic Anomalies - Retinopathy of Prematurity - Refeeding Edema. Perhaps these new investigations will convince pediatric cardiologists to reevaluate propranolol treatment, especially in infants with univentricular hearts in an effort to improve their very high mortality rate. Furthermore, there have been important findings suggesting that oral propranolol induces a significant decrease in endothelial nitric oxide synthase activity and vascular endothelial growth factor levels in children, both of which are important factors in the development of pulmonary vascular disease. Moreover, based upon our long-time data, we developed our “autonomic imprinting” model, that may explain how early life stress due to infant heart failure may impair growth and cognition, and increase cardiovascular risk in later life.
Article Details
How to Cite
BUCHHORN, Reiner; BORST, М. М..
The History and Future of Beta Blockers in Heart Failure Treatment in Children and Adults.
Medical Research Archives, [S.l.], v. 5, n. Issue 9, sep. 2017.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/1512>. Date accessed: 13 nov. 2024.
Keywords
heart failure, beta blocker, children, hemangioma, edema, pulmonary hypertension, autonomic imprinting, congenital heart disease
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
Reference List
(1) Buchhorn R, Bartmus D, Siekmeyer W et al. Beta-blocker therapy of severe congestive heart failure in infants with left to right shunts. Am J Cardiol 1998; 81(11):1366-1368.
(2) Ohye RG, Schonbeck JV, Eghtesady P et al. Cause, timing, and location of death in the Single Ventricle Reconstruction trial. J Thorac Cardiovasc Surg 2012; 144(4):907-914.
(3) Chatterjee S, Biondi-Zoccai G, Abbate A et al. Benefits of beta blockers in patients with heart failure and reduced ejection fraction: network meta-analysis. BMJ 2013; 346:f55.
(4) Waagstein F, Hjalmarson A, Varnauskas E et al. Effect of chronic beta-adrenergic receptor blockade in congestive cardiomyopathy. Br Heart J 1975; 37(10):1022-1036.
(5) Leaute-Labreze C, Dumas dlR, Hubiche T et al. Propranolol for severe hemangiomas of infancy. N Engl J Med 2008; 358(24):2649-2651.
(6) Filippi L, Dal Monte M, Casini G et al. Infantile hemangiomas, retinopathy of prematurity and cancer: a common pathogenetic role of the beta-adrenergic system. Med Res Rev 2015; 35(3):619-652.
(7) Schmaltz AA. Chronic congestive heart failure in infancy and childhood: new aspects of diagnosis and treatment. Klin Padiatr 2015; 227(1):3-9.
(8) Norozi K, Wessel A, Alpers V et al. Incidence and risk distribution of heart failure in adolescents and adults with congenital heart disease after cardiac surgery. Am J Cardiol 2006; 97(8):1238-1243.
(9) Raissadati A, Nieminen H, Haukka J et al. Late Causes of Death After Pediatric Cardiac Surgery: A 60-Year Population-Based Study. J Am Coll Cardiol 2016; 68(5):487-498.
(10) Inuzuka R, Tatebe S, Wakiguchi S et al. B-type natriuretic peptide at the early stage of univentricular circulation reflects inadequate adaptation to volume overload. Int J Cardiol 2012; 159(2):88-93.
(11) Miyamoto K, Takeuchi D, Inai K et al. Prognostic value of multiple biomarkers for cardiovascular mortality in adult congenital heart disease: comparisons of single-/two-ventricle physiology, and systemic morphologically right/left ventricles. Heart Vessels 2016; 31(11):1834-1847.
(12) Videbaek J, Laursen HB, Olsen M et al. A Long-Term Nationwide Follow-Up Study of Simple Congenital Heart Disease Diagnosed in Otherwise Healthy Children. Circulation 2016;133(5):474-83.
(13) Shaddy RE, Olsen SL, Bristow MR et al. Efficacy and safety of metoprolol in the treatment of doxorubicin-induced cardiomyopathy in pediatric patients. Am Heart J 1995; 129(1):197-199.
(14) Shaddy RE, Boucek MM, Hsu DT et al. Carvedilol for children and adolescents with heart failure: a randomized controlled trial. JAMA 2007; 298(10):1171-1179.
(15) Norozi K, Bahlmann J, Raab B et al. A prospective, randomized, double-blind, placebo controlled trial of beta-blockade in patients who have undergone surgical correction of tetralogy of Fallot. Cardiol Young 2007; 17(4):372-379.
(16) Buchhorn R, McConnell ME. Beta blockers in childhood heart failure - why not? Int J Cardiol 2014; 175(1):211-212.
(17) Prijic S, Buchhorn R, Kosutic J et al. Beta-Blockers (Carvedilol) in Children with Systemic Ventricle Systolic Dysfunction - Systematic Review and Meta-Analysis. Rev Recent Clin Trials 2014; 9(2):68-75.
(18) Hsu DT, Zak V, Mahony L et al. Enalapril in infants with single ventricle: results of a multicenter randomized trial. Circulation 2010; 122(4):333-340.
(19) Elkiran O, Sandikkaya A, Kocak G et al. Evaluation by N-terminal prohormone of brain natriuretic peptide concentrations and ross scoring of the efficacy of digoxin in the treatment of heart failure secondary to congenital heart disease with left-to-right shunts. Pediatr Cardiol 2013; 34(7):1583-1589.
(20) Buchhorn R, Hulpke-Wette M, Hilgers R et al. Propranolol treatment of congestive heart failure in infants with congenital heart disease: The CHF-PRO-INFANT Trial. Congestive heart failure in infants treated with propanol. Int J Cardiol 2001; 79(2-3):167-173.
(21) Ahuja RS, Ramakrishnan S, Kothari SS et al. Propranolol in infants with ventricular septal defects with heart failure (VSD-PHF Study). Ann Pediatr Cardiol 2013;6:105-8
(22) Ostman-Smith I. Beta-Blockers in Pediatric Hypertrophic Cardiomyopathies. Rev Recent Clin Trials 2014; 9(2):82-85.
(23) Ishikawa Y, Bach JR, Ishikawa Y et al. A management trial for Duchenne cardiomyopathy. Am J Phys Med Rehabil 1995; 74(5):345-350.
(24) Ghelani SJ, Spurney CF, Martin GR et al. Impact of pharmacotherapy on interstage mortality and weight gain in children with single ventricle. Congenit Heart Dis 2013; 8(3):219-227.
(25) Moffett BS, Price JF. National prescribing trends for heart failure medications in children. Congenit Heart Dis 2015; 10(1):78-85.
(26) Moffett BS, Humlicek TJ, Rossano JW et al. Readmissions for Heart Failure in Children. J Pediatr 2016; 177:153-158.
(27) Rossano JW, Kim JJ, Decker JA et al. Prevalence, morbidity, and mortality of heart failure-related hospitalizations in children in the United States: a population-based study. J Card Fail 2012; 18(6):459-470.
(28) Wittlieb-Weber CA, Lin KY, Zaoutis TE et al. Pediatric versus adult cardiomyopathy and heart failure-related hospitalizations: a value-based analysis. J Card Fail 2015; 21(1):76-82.
(29) Schranz D, Voelkel NF. "Nihilism" of chronic heart failure therapy in children and why effective therapy is withheld. Eur J Pediatr 2016; 175(4):445-455.
(30) Warmann S, Bertram H, Kardorff R et al. Interventional treatment of infantile hepatic hemangioendothelioma. J Pediatr Surg 2003; 38(8):1177-1181.
(31) Dotan M, Lorber A. Congestive heart failure with diffuse neonatal hemangiomatosis--case report and literature review. Acta Paediatr 2013; 102(5):e232-e238.
(32) You HS, Kim HS, Kim BS et al. Propranolol to treat infantile hemangioma (IH) in patients with congenital heart disease. J Am Acad Dermatol 2015; 72(5):912-914.
(33) Brazzelli V, Giorgini C, Barruscotti S et al. Efficacy of propranolol for cutaneous hemangiomas in premature children. G Ital Dermatol Venereol 2016; 151(5):485-491.
(34) Yi LF, Wen HX, Huang S et al. [Changes in ambulatory electrocardiographic findings after oral administration of low-dose propranolol in infants with hemangioma]. Zhongguo Dang Dai Er Ke Za Zhi 2016; 18(4):345-349.
(35) Moyakine AV, Spillekom-van Koulil S, van der Vleuten CJM. Propranolol treatment of infantile hemangioma is not associated with psychological problems at 7 years of age. J Am Acad Dermatol 2017; 77(1):105-108.
(36) Buchhorn R, Hammersen A, Bartmus D et al. The pathogenesis of heart failure in infants with congenital heart disease. Cardiol Young 2001; 11(5):498-504.
(37) Buchhorn R, Motz R. Hepatic encephalopathy and ascites. Lancet 1998; 351(9100):448-449.
(38) Buchhorn R, Bartmus D, Buhre W et al. Pathogenetic mechanisms of venous congestion after the Fontan procedure. Cardiol Young 2001; 11(2):161-168.
(39) Ozeki M, Fukao T, Kondo N. Propranolol for intractable diffuse lymphangiomatosis. N Engl J Med 2011; 364(14):1380-1382.
(40) Wu JK, Hooper ED, Laifer-Narin SL et al. Initial Experience With Propranolol Treatment of Lymphatic Anomalies: A Case Series. Pediatrics 2016; 138(3).
(41) Buchhorn R, Bauman C, Willaschek C. Propranolol is highly effective to treat refeeding oedema in a girl with anorexia nervosa - a case report. Ann Nutr Disord Ther 2017; 4(1):1039.
(42) Black SM, Kumar S, Wiseman D et al. Pediatric pulmonary hypertension: Roles of endothelin-1 and nitric oxide. Clin Hemorheol Microcirc 2007; 37(1-2):111-120.
(43) Takaya J, Ikemoto Y, Teraguchi M et al. Plasma nitric oxide products correlate with cardiac index of congenital heart disease. Pediatr Cardiol 2000; 21(4):378-381.
(44) Buchhorn R, Wessel A, Hulpke-Wette M et al. Endogenous nitric oxide and soluble tumor necrosis factor receptor levels are enhanced in infants with congenital heart disease. Crit Care Med 2001; 29(11):2208-2210.
(45) Yuan WL, Jin ZL, Wei JJ et al. Propranolol given orally for proliferating infantile haemangiomas: analysis of efficacy and serological changes in vascular endothelial growth factor and endothelial nitric oxide synthase in 35 patients. Br J Oral Maxillofac Surg 2013; 51(7):656-661.
(46) Buchhorn R, Hulpke-Wette M, Wessel A et al. Beta-blocker therapy in an infant with pulmonary hypertension. Eur J Pediatr 1999; 158(12):1007-1008.
(47) Ramakrishnan S, Vyas C, Kothari SS et al. Acute and short-term hemodynamic effects of metoprolol in Eisenmenger syndrome: a preliminary observational study. Am Heart J 2011; 161(5):938-943.
(48) Perros F, Ranchoux B, Izikki M et al. Nebivolol for improving endothelial dysfunction, pulmonary vascular remodeling, and right heart function in pulmonary hypertension. J Am Coll Cardiol 2015; 65(7):668-680.
(49) Rubin LJ. The beta-adrenergic receptor in pulmonary arterial hypertension: a novel therapeutic target? J Am Coll Cardiol 2015; 65(7):681-683.
(50) Chen SL, Zhang H, Xie DJ et al. Hemodynamic, functional, and clinical responses to pulmonary artery denervation in patients with pulmonary arterial hypertension of different causes: phase II results from the Pulmonary Artery Denervation-1 study. Circ Cardiovasc Interv 2015; 8(11):e002837.
(51) Willaschek C, Meint S, Rager K et al. Modified Clonidine Testing for Growth Hormone Stimulation Reveals alpha2-Adrenoreceptor Sub Sensitivity in Children with Idiopathic Growth Hormone Deficiency. PLoS ONE 2015; 10(9):e0137643.
(52) Buchhorn R, Meint S, Willaschek C. The Impact of Early Life Stress on Growth and Cardiovascular Risk: A Possible Example for Autonomic Imprinting? PLoS ONE 2016; 11(11):e0166447.
(53) Buchhorn R, Hauk F, Meint S, Willaschek C (2016). The impact of nutrition on the autonomic nervous system. Int J Food Nutr Sci 3 (3) :1-16
54) Buchhorn R, Willaschek C, Norozi K (2016). Medical treatment of heart failure in infancy has long term effects on the autonomic nervous system – The concept of autonomic imprinting. https://www.researchgate.net/ publication/303937266_Heart_and_Cardiolgy_Open_Access_Medical_Treatment_of_Heart_Failure_in_Infancy_has_Long_Term_Effects_on_the_Autonomic_Nervous_System_-_The_Concept_of_Autonomic_Imprinting
(55) Buchhorn R, Motz R, Norozi K (2016). Heart Failure in Infants with Congenital Heart Defects – The Concept of Autonomic Imprinting. https://www.researchgate.net/publication/303937424_Heart_and_Cardiolgy_Open_Access_Heart_Failure_in_Infants_with_Congenital_Heart_Defects_-_The_Concept_of_Autonomic_ Imprinting
(1) Buchhorn R, Bartmus D, Siekmeyer W et al. Beta-blocker therapy of severe congestive heart failure in infants with left to right shunts. Am J Cardiol 1998; 81(11):1366-1368.
(2) Ohye RG, Schonbeck JV, Eghtesady P et al. Cause, timing, and location of death in the Single Ventricle Reconstruction trial. J Thorac Cardiovasc Surg 2012; 144(4):907-914.
(3) Chatterjee S, Biondi-Zoccai G, Abbate A et al. Benefits of beta blockers in patients with heart failure and reduced ejection fraction: network meta-analysis. BMJ 2013; 346:f55.
(4) Waagstein F, Hjalmarson A, Varnauskas E et al. Effect of chronic beta-adrenergic receptor blockade in congestive cardiomyopathy. Br Heart J 1975; 37(10):1022-1036.
(5) Leaute-Labreze C, Dumas dlR, Hubiche T et al. Propranolol for severe hemangiomas of infancy. N Engl J Med 2008; 358(24):2649-2651.
(6) Filippi L, Dal Monte M, Casini G et al. Infantile hemangiomas, retinopathy of prematurity and cancer: a common pathogenetic role of the beta-adrenergic system. Med Res Rev 2015; 35(3):619-652.
(7) Schmaltz AA. Chronic congestive heart failure in infancy and childhood: new aspects of diagnosis and treatment. Klin Padiatr 2015; 227(1):3-9.
(8) Norozi K, Wessel A, Alpers V et al. Incidence and risk distribution of heart failure in adolescents and adults with congenital heart disease after cardiac surgery. Am J Cardiol 2006; 97(8):1238-1243.
(9) Raissadati A, Nieminen H, Haukka J et al. Late Causes of Death After Pediatric Cardiac Surgery: A 60-Year Population-Based Study. J Am Coll Cardiol 2016; 68(5):487-498.
(10) Inuzuka R, Tatebe S, Wakiguchi S et al. B-type natriuretic peptide at the early stage of univentricular circulation reflects inadequate adaptation to volume overload. Int J Cardiol 2012; 159(2):88-93.
(11) Miyamoto K, Takeuchi D, Inai K et al. Prognostic value of multiple biomarkers for cardiovascular mortality in adult congenital heart disease: comparisons of single-/two-ventricle physiology, and systemic morphologically right/left ventricles. Heart Vessels 2016; 31(11):1834-1847.
(12) Videbaek J, Laursen HB, Olsen M et al. A Long-Term Nationwide Follow-Up Study of Simple Congenital Heart Disease Diagnosed in Otherwise Healthy Children. Circulation 2016;133(5):474-83.
(13) Shaddy RE, Olsen SL, Bristow MR et al. Efficacy and safety of metoprolol in the treatment of doxorubicin-induced cardiomyopathy in pediatric patients. Am Heart J 1995; 129(1):197-199.
(14) Shaddy RE, Boucek MM, Hsu DT et al. Carvedilol for children and adolescents with heart failure: a randomized controlled trial. JAMA 2007; 298(10):1171-1179.
(15) Norozi K, Bahlmann J, Raab B et al. A prospective, randomized, double-blind, placebo controlled trial of beta-blockade in patients who have undergone surgical correction of tetralogy of Fallot. Cardiol Young 2007; 17(4):372-379.
(16) Buchhorn R, McConnell ME. Beta blockers in childhood heart failure - why not? Int J Cardiol 2014; 175(1):211-212.
(17) Prijic S, Buchhorn R, Kosutic J et al. Beta-Blockers (Carvedilol) in Children with Systemic Ventricle Systolic Dysfunction - Systematic Review and Meta-Analysis. Rev Recent Clin Trials 2014; 9(2):68-75.
(18) Hsu DT, Zak V, Mahony L et al. Enalapril in infants with single ventricle: results of a multicenter randomized trial. Circulation 2010; 122(4):333-340.
(19) Elkiran O, Sandikkaya A, Kocak G et al. Evaluation by N-terminal prohormone of brain natriuretic peptide concentrations and ross scoring of the efficacy of digoxin in the treatment of heart failure secondary to congenital heart disease with left-to-right shunts. Pediatr Cardiol 2013; 34(7):1583-1589.
(20) Buchhorn R, Hulpke-Wette M, Hilgers R et al. Propranolol treatment of congestive heart failure in infants with congenital heart disease: The CHF-PRO-INFANT Trial. Congestive heart failure in infants treated with propanol. Int J Cardiol 2001; 79(2-3):167-173.
(21) Ahuja RS, Ramakrishnan S, Kothari SS et al. Propranolol in infants with ventricular septal defects with heart failure (VSD-PHF Study). Ann Pediatr Cardiol 2013;6:105-8
(22) Ostman-Smith I. Beta-Blockers in Pediatric Hypertrophic Cardiomyopathies. Rev Recent Clin Trials 2014; 9(2):82-85.
(23) Ishikawa Y, Bach JR, Ishikawa Y et al. A management trial for Duchenne cardiomyopathy. Am J Phys Med Rehabil 1995; 74(5):345-350.
(24) Ghelani SJ, Spurney CF, Martin GR et al. Impact of pharmacotherapy on interstage mortality and weight gain in children with single ventricle. Congenit Heart Dis 2013; 8(3):219-227.
(25) Moffett BS, Price JF. National prescribing trends for heart failure medications in children. Congenit Heart Dis 2015; 10(1):78-85.
(26) Moffett BS, Humlicek TJ, Rossano JW et al. Readmissions for Heart Failure in Children. J Pediatr 2016; 177:153-158.
(27) Rossano JW, Kim JJ, Decker JA et al. Prevalence, morbidity, and mortality of heart failure-related hospitalizations in children in the United States: a population-based study. J Card Fail 2012; 18(6):459-470.
(28) Wittlieb-Weber CA, Lin KY, Zaoutis TE et al. Pediatric versus adult cardiomyopathy and heart failure-related hospitalizations: a value-based analysis. J Card Fail 2015; 21(1):76-82.
(29) Schranz D, Voelkel NF. "Nihilism" of chronic heart failure therapy in children and why effective therapy is withheld. Eur J Pediatr 2016; 175(4):445-455.
(30) Warmann S, Bertram H, Kardorff R et al. Interventional treatment of infantile hepatic hemangioendothelioma. J Pediatr Surg 2003; 38(8):1177-1181.
(31) Dotan M, Lorber A. Congestive heart failure with diffuse neonatal hemangiomatosis--case report and literature review. Acta Paediatr 2013; 102(5):e232-e238.
(32) You HS, Kim HS, Kim BS et al. Propranolol to treat infantile hemangioma (IH) in patients with congenital heart disease. J Am Acad Dermatol 2015; 72(5):912-914.
(33) Brazzelli V, Giorgini C, Barruscotti S et al. Efficacy of propranolol for cutaneous hemangiomas in premature children. G Ital Dermatol Venereol 2016; 151(5):485-491.
(34) Yi LF, Wen HX, Huang S et al. [Changes in ambulatory electrocardiographic findings after oral administration of low-dose propranolol in infants with hemangioma]. Zhongguo Dang Dai Er Ke Za Zhi 2016; 18(4):345-349.
(35) Moyakine AV, Spillekom-van Koulil S, van der Vleuten CJM. Propranolol treatment of infantile hemangioma is not associated with psychological problems at 7 years of age. J Am Acad Dermatol 2017; 77(1):105-108.
(36) Buchhorn R, Hammersen A, Bartmus D et al. The pathogenesis of heart failure in infants with congenital heart disease. Cardiol Young 2001; 11(5):498-504.
(37) Buchhorn R, Motz R. Hepatic encephalopathy and ascites. Lancet 1998; 351(9100):448-449.
(38) Buchhorn R, Bartmus D, Buhre W et al. Pathogenetic mechanisms of venous congestion after the Fontan procedure. Cardiol Young 2001; 11(2):161-168.
(39) Ozeki M, Fukao T, Kondo N. Propranolol for intractable diffuse lymphangiomatosis. N Engl J Med 2011; 364(14):1380-1382.
(40) Wu JK, Hooper ED, Laifer-Narin SL et al. Initial Experience With Propranolol Treatment of Lymphatic Anomalies: A Case Series. Pediatrics 2016; 138(3).
(41) Buchhorn R, Bauman C, Willaschek C. Propranolol is highly effective to treat refeeding oedema in a girl with anorexia nervosa - a case report. Ann Nutr Disord Ther 2017; 4(1):1039.
(42) Black SM, Kumar S, Wiseman D et al. Pediatric pulmonary hypertension: Roles of endothelin-1 and nitric oxide. Clin Hemorheol Microcirc 2007; 37(1-2):111-120.
(43) Takaya J, Ikemoto Y, Teraguchi M et al. Plasma nitric oxide products correlate with cardiac index of congenital heart disease. Pediatr Cardiol 2000; 21(4):378-381.
(44) Buchhorn R, Wessel A, Hulpke-Wette M et al. Endogenous nitric oxide and soluble tumor necrosis factor receptor levels are enhanced in infants with congenital heart disease. Crit Care Med 2001; 29(11):2208-2210.
(45) Yuan WL, Jin ZL, Wei JJ et al. Propranolol given orally for proliferating infantile haemangiomas: analysis of efficacy and serological changes in vascular endothelial growth factor and endothelial nitric oxide synthase in 35 patients. Br J Oral Maxillofac Surg 2013; 51(7):656-661.
(46) Buchhorn R, Hulpke-Wette M, Wessel A et al. Beta-blocker therapy in an infant with pulmonary hypertension. Eur J Pediatr 1999; 158(12):1007-1008.
(47) Ramakrishnan S, Vyas C, Kothari SS et al. Acute and short-term hemodynamic effects of metoprolol in Eisenmenger syndrome: a preliminary observational study. Am Heart J 2011; 161(5):938-943.
(48) Perros F, Ranchoux B, Izikki M et al. Nebivolol for improving endothelial dysfunction, pulmonary vascular remodeling, and right heart function in pulmonary hypertension. J Am Coll Cardiol 2015; 65(7):668-680.
(49) Rubin LJ. The beta-adrenergic receptor in pulmonary arterial hypertension: a novel therapeutic target? J Am Coll Cardiol 2015; 65(7):681-683.
(50) Chen SL, Zhang H, Xie DJ et al. Hemodynamic, functional, and clinical responses to pulmonary artery denervation in patients with pulmonary arterial hypertension of different causes: phase II results from the Pulmonary Artery Denervation-1 study. Circ Cardiovasc Interv 2015; 8(11):e002837.
(51) Willaschek C, Meint S, Rager K et al. Modified Clonidine Testing for Growth Hormone Stimulation Reveals alpha2-Adrenoreceptor Sub Sensitivity in Children with Idiopathic Growth Hormone Deficiency. PLoS ONE 2015; 10(9):e0137643.
(52) Buchhorn R, Meint S, Willaschek C. The Impact of Early Life Stress on Growth and Cardiovascular Risk: A Possible Example for Autonomic Imprinting? PLoS ONE 2016; 11(11):e0166447.
(53) Buchhorn R, Hauk F, Meint S, Willaschek C (2016). The impact of nutrition on the autonomic nervous system. Int J Food Nutr Sci 3 (3) :1-16
54) Buchhorn R, Willaschek C, Norozi K (2016). Medical treatment of heart failure in infancy has long term effects on the autonomic nervous system – The concept of autonomic imprinting. https://www.researchgate.net/ publication/303937266_Heart_and_Cardiolgy_Open_Access_Medical_Treatment_of_Heart_Failure_in_Infancy_has_Long_Term_Effects_on_the_Autonomic_Nervous_System_-_The_Concept_of_Autonomic_Imprinting
(55) Buchhorn R, Motz R, Norozi K (2016). Heart Failure in Infants with Congenital Heart Defects – The Concept of Autonomic Imprinting. https://www.researchgate.net/publication/303937424_Heart_and_Cardiolgy_Open_Access_Heart_Failure_in_Infants_with_Congenital_Heart_Defects_-_The_Concept_of_Autonomic_ Imprinting