Rethinking Tako-tsubo Cardiomyopathy: The Contribution of Myocardial Pathology and Molecular Imaging.

BACKGROUND: Despite substantial research, the mechanisms behind stress Tako-tsubo cardiomyopathy (TTC) remain rather elusive. OBJECTIVE: The purpose of this paper was to provide a detailed review of the mainstream factors underlying the pathophysiology of TTC, highlighting the novel contributions of molecular pathology and in-vivo molecular imaging. METHODS: A careful literature review selected all papers discussing TTC, specifically those providing novel insights from myocardial pathology and cardiac molecular imaging. RESULTS: Results concerning myocardial pathology, defect extension, sites and relationships between functional parameters underline the existence of a causal relationship between a determinant (e.g., the release of catecholamines induced by stress) and an outcome for TTC, which is not limited to a reversible contractile cardiomyopathy, but it includes reversible changes in myocardial perfusion and a long-lasting residual deficit in sympathetic function. Besides, they reinforce the hypothesis that sympathetic nerves may exert a complex control on cardiac contractile function, which is likely to be direct or indirect through metabolism and microvascular perfusion changes during anaerobic and aerobic conditions. CONCLUSION: TTC is characterized by acute transient left ventricular systolic dysfunction, which can be challenging to distinguish from myocardial infarction at presentation. Catecholamineinduced myocardial injury is the most established theory, but other factors, including myocardial metabolism and perfusion, should be considered of utmost importance. Each effort to clarify the numerous pathways and emerging abnormalities may provide novel approaches to treat the acute episode, avoid recurrences, and prevent major adverse cardiovascular events.

Neurobiological Dysfunctional Substrates for the Self-Medication Hypothesis in Adult Individuals with Attention-Deficit Hyperactivity Disorder and Cocaine Use Disorder: A Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography Study.

Objectives: Attention-deficit hyperactivity disorder (ADHD) in adulthood shows high co-occurrence rates with cocaine use disorder (CoUD). The self-medication hypothesis (SMH) provides a theoretical explanation for this comorbidity. This study investigates the neurobiological mechanisms that could support SMH in adult patients with attention-deficit hyperactivity disorder with cocaine use disorder (ADHD-CoUD). Materials and Methods: We included 19 ADHD-CoUD patients (84.2% male; age: 32.11 years [7.18]) and 16 CoUD patients (68.7% male; age: 36.63 years [8.12]). All subjects underwent a fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) brain scan. We tested brain metabolism differences between ADHD-CoUD and CoUD patients using voxel-based and regions of interest (ROIs)-based analyses. The correlation between dependence/abstinence duration and regional brain metabolism was also assessed in the two groups. Lastly, we investigated the integrity of brain metabolic connectivity of mesocorticolimbic and nigrostriatal dopaminergic systems, and large-scale brain networks involved in ADHD and addictions. Results: The voxel-wise and ROIs-based approaches showed that ADHD-CoUD patients had a lower metabolism in the thalamus and increased metabolism in the amygdala and parahippocampus, bilaterally, than CoUD subjects and healthy controls (HCs). Metabolism in the thalamus negatively correlated with years of dependence in ADHD-CoUD patients. Moreover, connectivity analyses revealed that ADHD-CoUD patients had a more preserved metabolic connectivity than CoUD patients in the dopaminergic networks and large-scale networks involved in self-regulation mechanisms of attention and behaviors (i.e., anterior default mode network [ADMN], executive network [ECN], and anterior salience network [aSAN]). Conclusions: We demonstrated distinct neuropathological substrates underlying substance-use behaviors in ADHD-CoUD and CoUD patients. Furthermore, we provided neurobiological evidence in support of SMH, demonstrating that ADHD-CoUD patients might experience short-term advantages of cocaine assumption (i.e., compensation of dopaminergic deficiency and related cognitive-behavioral deficits).

The natural history of takotsubo syndrome: a two-year follow-up study with myocardial sympathetic and perfusion G-SPECT imaging.

PURPOSE: To investigate changes in sympathetic activity, perfusion, and left ventricular (LV) functionality in takotsubo cardiomyopathy (TTC) patients from onset (T0) to post-onset conditions at 1 month (T1), 1-2 years (T2, T3). METHODS: Twenty-two patients (70 ± 11 years) underwent serial gated single photon emission tomography (G-SPECT) studies with 123I-mIBG and 99mTc-Sestamibi. Statistics were performed using ANOVA/Sheffé post-hoc, correlation test, and receiver operating characteristic (ROC) curve analysis (p < 0.05). RESULTS: Patients presented at T0 with LV ballooning and reduced early-late mIBG uptake (95%, 100%), left ventricular ejection fraction (LVEF)G-SPECT (86%) and perfusion (77 %). Adrenergic dysfunction was greater in apex, it overlaps with contractile impairment, and both were more severe than perfusion defect. During follow-up, LVEFG-SPECT, contractility, and perfusion were normal, while 82% and 90% of patients at T1 and 50% at T2 and T3 continued to show a reduced apical early-late mIBG distribution. These patients presented at T0-T1 with greater impairment of adrenergic function, contractility, and perfusion. A relationship was present within innervation and both perfusion and contractile parameters at T0 and T1, and between the extent of adrenergic defect at T3 and both the defect extent and age at T0 (cut-off point 42.5%, 72 years). CONCLUSION: Outcome for TTC is not limited to a reversible contractile and perfusion abnormalities, but it includes residual adrenergic dysfunction, depending on the level of adrenergic impairment and age of patients at onset. The number of patients, as well as degree of perfusion abnormalities were found to be higher than those previously reported possibly depending on the time-interval between hospital admission and perfusion scan.

Brain Network Underlying the Improvement of Social Functioning in Schizophrenic Patients After One-year Treatment with Social Skills Training.

PURPOSE: To assess changes in social and neuro-cognition and regional cerebral blood flow (rCBF) in schizophrenic patients with psychotic syndrome treated with Social Skill Training (SST). METHODS: 17 patients underwent two high resolution rCBF SPECT at rest before and after a one-year treatment with SST. Patients were assessed using a neuropsychological evaluation (W.A.I.S.-R, T.M.T, Verbal Fluency, W.C.S.T.). SPM8 was used to investigate rCBF changes from the pre- to the post-SST condition and the relationship between rCBF and clinical scores used as covariates of interest. RESULTS: All patients presented with an improvement in social perception, ability to deal with abstract social conventions, rules and judgments about people (Comprehension and Picture Completion sub-tests) and some neuro-cognitive functions sustaining the process of socially relevant information. The main effect of SST was to produce rCBF increases in precuneus, PCC, superior parietal lobules, PMC, pre-SMA, precentral gyrus, dmPFC, dlPFC, vmPFC, OFC (p<0.0001 uncorrected). The SPM analysis showed that Comprehension was supported by PMC, dmPFC, OFC and vmPFC, while the Picture Completion was supported by PMC and dmPFC (p<0.0001). CONCLUSION: SST in schizophrenic patients improves resting neural activity in cortical areas of the amigdala-based and non-amygdala networks of social brain, including dmPFC and vmPFC, and dlPFC, which are known to be part of default mode and task-positive networks and to be implicated in schizophrenia.