Sympathetic Heart Innervation in Patients With Tako-Tsubo Cardiomyopathy
Condition: Apical Ballooning Syndrome; Nervous System Diseases, Sympathetic
MeSH terms: Nervous System Diseases; Autonomic Nervous System Diseases; Cardiomyopathies; Takotsubo Cardiomyopathy
Study type: Interventional
Phase: Phase 4

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-lipoic acid and L-acetyl carnitine, will improve the adrenergic cardiac innervation, in
      patients with SC.
    

Detailed description: 
      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.
    

Intervention name(s): Placebo; alpha-lipoic acid; L-acetyl carnitine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): a placebo tablet bis in die for 12 months; alpha-lipoic, tablets of acid 400 mg bis in die (800 mg/day), for 12 months; L-acetyl carnitine tablets, 500 mg bis in die (1000 mg/day), for 12 months
Intervention MeSH terms: Thioctic Acid; Acetylcarnitine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Tako-Tsubo; Sympathetic heart innervation; MIBG; Alpha-lipoic acid; L-acetyl carnitine