Clinical Trial: Sympathetic Heart Innervation in Patients With Tako-Tsubo Cardiomyopathy

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 Carn

Brief Summary:

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-

Detailed Summary:

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
Sponsor: Second University of Naples

Current Primary Outcome: 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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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.


Original Secondary Outcome: Same as current

Information By: Second University of Naples

Dates:
Date Received: January 23, 2012
Date Started: December 2011
Date Completion:
Last Updated: January 26, 2016
Last Verified: January 2016