Sympathetic Heart Innervation in Patients With Tako-Tsubo Cardiomyopathy
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01524861|
Recruitment Status : Completed
First Posted : February 2, 2012
Last Update Posted : January 27, 2016
Stress (tako-tsubo) cardiomyopathy (SC) is a rapidly reversible form of acute heart failure reported to be triggered by stressful events and associated with a distinctive left ventricular (LV) contraction pattern.
SC mimics acute coronary syndrome and is accompanied by reversible left ventricular apical ballooning in the absence of angiographically significant coronary artery stenosis. sympathetic activity dysfunction appears to play a very important role in the pathophysiology of takotsubo cardiomyopathy.
In most cases, myocardial scintillography with 123Imetaiodobenzylguanidine (MIBG) showed altered captation of the radiotracer in several heart segments. In particular, the apical myocardium has poor sympathetic innervations and an uptake reduction in MIBG tracer.
A hypothesis for this finding could be that the intense discharge of adrenalin, acting on heart segment with different and abnormal innervation, may produce a transient heart failure characterized by a particular shape of the left ventricle.
While studies have shown that heterogeneous MIBG distribution, decreased MIBG uptake and increased norepinephrine content were completely prevented by α-lipoic acid or by L-acetyl carnitine administrations in diabetic cardiomyopathy, no studies have examined the effects of these therapies on tako-tsubo cardiomyopathy.
On this basis, the investigators study will evaluate whether the dysfunction of adrenergic cardiac innervation, evaluated by MIBG, persist after previous experience of transient stress-induced cardiac dysfunction. Moreover, the investigators will assess whether the medications that restore sympatho-vagal alterations in diabetic cardiomyopathy, such as α-lipoic acid and L-acetyl carnitine, will improve the adrenergic cardiac innervation, in patients with SC.
|Condition or disease||Intervention/treatment||Phase|
|Apical Ballooning Syndrome Nervous System Diseases, Sympathetic||Drug: Placebo Drug: alpha-lipoic acid Drug: L-acetyl carnitine||Phase 4|
Study design Each patient will be assessed with history and physical examination, 12-lead ECG, serum troponin, coronary arteriography, and LV angiogram (an average of 6 hours after admission to the hospital), with echocardiography and 123Imetaiodobenzylguanidine (MIBG) myocardial scintillography. All patients were admitted to the cardiac care unit after coronary angiography. Currently recommended treatments for acute coronary syndromes (ACS), with therapy directed at relieving myocardial ischemia and preventing thrombotic complications, were provided to all patients. For each patient, the Charlson score index, 8 which represents the most studied and evaluated comorbidity index, will be calculated. At discharge, surviving patients with established SC will be managed and followed for 12 month after the event, as outpatients. At discharge, the surviving patients will be randomly assigned to alpha-lipoic acid 800 mg/day treatment (ALA group), or L-acetyl carnitine 1000 mg/day treatment (LAC group) or placebo (control group). With regard to the full medical therapy, the protocol stated that the use of concomitant treatment should be uniform, between the groups, and according to evidence-based international guidelines for ACS in all patients. Following discharge, patients were asked to return to our outpatient clinic for follow-up evaluation at 6 and 12 months after the initial event of SC.
Coronary Angiography Coronary angiograms at baseline, immediately after percutaneous coronary intervention (PCI) will be performed in at least 2 orthogonal views after intracoronary nitroglycerin. The analyses of all angiographic data will be performed by operators who were unaware of the study groups (Toshiba, Infinix CS-i).
Echocardiography LV function will be evaluated in all patients by two-dimensional echocardiography at admission, 6 and 12 months after the discharge.
MIBG imaging. MIBG imaging will be performed in all patients shortly after admission and at 6 and 12 months after the discharge. MIBG will be performed with a The standard protocol for 123I-MIBG cardiac imaging requires that drugs that interfere with 123I-MIBG uptake be withheld. A comprehensive listing of prescription and over-the-counter drugs that interfere with 123I-MIBG biodistribution, and the time for which they should be withheld, has been published . Thyroid uptake of unbound 123I is blocked with 500 mg of potassium perchlorate given orally 30 min before 123I-MIBG injection. Between 148 MBq and 370 MBq of 123I-MIBG are injected intravenously at rest. Both planar and SPECT images are acquired 15 min after injection (early) and 4 h after injection (delayed). A dual head gammacamera (ECAM Siemens, Erlangen - Germany) equipped with a low-energy - high resolution collimator was used. A 20% window is usually centered over the 159-keV photopeak of 123I for imaging. Anterior planar images of the chest are acquired using a 256 x 256 matrix. single photon emission computed tomography (SPECT) images are acquired using a 64 x 64 matrix over 180°, from the right anterior oblique position to the left posterior oblique position. Planar imaging allows for global assessment of cardiac innervation, whereas SPECT allows for regional evaluation. Quantitative evaluations will be performed with a standard protocol previously described.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||90 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Care Provider)|
|Official Title:||Sympathetic Heart Innervation in Patients With Previous Experience of Transient Stress-induced Cardiomyopathy (Tako-Tsubo): Effects of α-lipoic Acid and L-acetyl Carnitine Therapies.|
|Study Start Date :||December 2011|
|Actual Primary Completion Date :||December 2015|
|Actual Study Completion Date :||January 2016|
Placebo Comparator: Placebo
30 subjects receive placebo (placebo group)
a placebo tablet bis in die for 12 months
Experimental: alpha-lipoic acid
30 subjects receive alpha-lipoic acid, 400 mg/day per os bis in die (800 mg/day)(ALA group)
Drug: alpha-lipoic acid
alpha-lipoic, tablets of acid 400 mg bis in die (800 mg/day), for 12 months
30 subjects receive L-acetyl carnitine, 500 mg per os bis in die (1000 mg/day) (LAC group)
Drug: L-acetyl carnitine
L-acetyl carnitine tablets, 500 mg bis in die (1000 mg/day), for 12 months
- Change from Baseline in Adrenergic cardiac innervation at 6 and 12 months [ Time Frame: 0, 6 and 12 months ]The improvement of adrenergic cardiac innervation as determined by quantitative MIBG
- Change from Baseline in the markers of inflammation at 6 and 12 months [ Time Frame: 0, 6 and 12 months ]Serum concentrations of IL-6 and IL-18 will be determined using a highly sensitive, quantitative sandwich enzyme assay. High-sensitivity TNF-α will assayed by immune-nephelometry. CRP will be determined using automated turbidimetry.
- Change from Baseline in the markers of oxidative stress at 6 and 12 months [ Time Frame: 0, 6 and 12 months ]Nitrotyrosine plasma concentration, will be assayed by enzyme-linked immunosorbent assay.
- Change from Baseline in the markers of myocardial damage at 6 and 12 months [ Time Frame: 0, 6 and 12 months ]Serum levels of Troponin I, miR-1, miR-133a, and miR-499 will be evaluated.
- Change from Baseline in the markers of sympathetic tone at 6 and 12 months [ Time Frame: 0, 6 and 12 months ]Plasma levels of catecholamines and their metabolites will measured by HPLC; brain natriuretic peptide and neuropeptide Y will be measured by enzyme immunoassay.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01524861
|Dept Geriatric and Metabolic diseases SUN|
|Principal Investigator:||Raffaele Marfella, MD, PhD||University of Campania "Luigi Vanvitelli"|
|Principal Investigator:||Raffaele Marfella, MD, PhD||Dept Geriatric and Metabolic diseases SUN, Naples, Italy|