Effects of α-lipoic acid therapy on sympathetic heart innervation in patients with previous experience of transient takotsubo cardiomyopathy.
BACKGROUND
Takotsubo syndrome is a stress cardiomyopathy, characterized by reversible left ventricle (LV) apical ballooning in the absence of significant angiographic coronary artery stenosis. The frequent association with emotional stress suggests in this disease an autonomic nervous system involvement. We could think that a therapeutic treatment targeting heart sympathetic dysfunction could be of crucial importance.


METHODS
From January 2010 to June 2012, 886 patients were consecutively evaluated at Cardarelli Hospital, Naples, Italy. Among these, 48 patients met takotsubo cardiomyopathy (TCM) criteria. Each patient was assessed with history and physical examination, 12-lead electrocardiogram, serum troponin, coronary arteriography, and left ventricular angiogram, perfusion myocardial scintigraphy with technetium 99m, with echocardiography and 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. At discharge, the surviving patients were randomly assigned to α-lipoic acid (ALA) treatment (600mg once daily) or placebo. Following discharge, after the initial TCM event, patients returned to our outpatient clinic at Internal Medicine of the Second University Naples for the follow-up evaluation quarterly until 12 months. Routine analysis, myocardial damage serum markers, oxidative stress serum markers, pro-inflammatory cytokines, and sympathetic tone activity were evaluated in all patients.


RESULTS
ALA administration improved MIBG defect size at 12 months compared to placebo.


CONCLUSIONS
Adrenergic cardiac innervation dysfunction in TCM patients persists after previous experience of transient stress-induced cardiac dysfunction. ALA treatment improves the adrenergic cardiac innervation. This study evaluates whether sympatho-vagal alterations are TCM event-related.
Department of Medical, Surgical, Neurological, Aging and Metabolic Sciences, Second University of Naples, Naples, Italy.
Raffaele
R
Marfella
Department of Medical, Surgical, Neurological, Aging and Metabolic Sciences, Second University of Naples, Naples, Italy.
Michelangela
M
Barbieri
Department of Medical, Surgical, Neurological, Aging and Metabolic Sciences, Second University of Naples, Naples, Italy. Electronic address: drsarducele@gmail.com.
Celestino
C
Sardu
Department of Medical, Surgical, Neurological, Aging and Metabolic Sciences, Second University of Naples, Naples, Italy.
Maria Rosaria
MR
Rizzo
Department of Cardiology, Hospital Cardarelli, Naples, Italy.
Mario
M
Siniscalchi
Department of Medical, Surgical, Neurological, Aging and Metabolic Sciences, Second University of Naples, Naples, Italy.
Pasquale
P
Paolisso
Department of Medical, Surgical, Neurological, Aging and Metabolic Sciences, Second University of Naples, Naples, Italy.
Maria
M
Ambrosino
Department of Medical, Surgical, Neurological, Aging and Metabolic Sciences, Second University of Naples, Naples, Italy.
Ilaria
I
Fava
Department of Cardiology, Hospital Cardarelli, Naples, Italy.
Crescenzo
C
Materazzi
Department of Cardiology, Hospital Cardarelli, Naples, Italy.
Giorgio
G
Cinquegrana
Department of Cardiology, Hospital Cardarelli, Naples, Italy.
Rossella
R
Gottilla
Department of Cardiology, Hospital Cardarelli, Naples, Italy.
Luigi Raffaele
LR
Elia
Department of Cardiology, Hospital Cardarelli, Naples, Italy.
Davide
D
D'andrea
Department of Cardiology, Sorrento Hospital, Naples, Italy.
Antonino
A
Coppola
Diagnostic Imaging Department, Second University of Naples, Naples, Italy.
Pier Francesco
PF
Rambaldi
Department of Cardiology, Hospital Cardarelli, Naples, Italy.
Ciro
C
Mauro
Diagnostic Imaging Department, Second University of Naples, Naples, Italy.
Luigi
L
Mansi
Department of Medical, Surgical, Neurological, Aging and Metabolic Sciences, Second University of Naples, Naples, Italy.
Giuseppe
G
Paolisso
D019797:3-Iodobenzylguanidine; D000368:Aged; D000975:Antioxidants / Q000627:therapeutic use; D017023:Coronary Angiography; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000294:innervation*; D006352:Heart Ventricles; D006801:Humans; D008875:Middle Aged; D055414:Myocardial Perfusion Imaging / Q000379:methods; D018384:Oxidative Stress / Q000187:drug effects; D017698:Postmenopause; D013315:Stress, Psychological / Q000150:complications; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013565:Sympatholytics / Q000627:therapeutic use*; D054549:Takotsubo Cardiomyopathy / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008063:Thioctic Acid / Q000627:therapeutic use*; D014336:Troponin / Q000097:blood
D000975:Antioxidants; D016207:Cytokines; D013565:Sympatholytics; D014336:Troponin; D019797:3-Iodobenzylguanidine; D008063:Thioctic Acid
Nitric oxide; Sympathetic heart innervation; Takotsubo cardiomyopathy; α-Lipoic acid