Presumed Takotsubo syndrome is associated with high in-hospital mortality in very elderly frail females: a case series.

Given the aging of general population, very elderly females with Takotsubo syndrome (TTS) are not rarely encountered in clinical practice. Although coronary angiography with left ventriculography is the gold standard diagnostic tool to exclude or confirm TTS, currently, this invasive procedure is less frequently performed in older patients with several comorbidities, such as renal failure, anemia, infections, neurological disorders, malignancy, and severe frailty. In these patients, a "presumed" TTS is diagnosed on the basis of clinical presentation, electrocardiogram, cardiac biomarkers, and echocardiographic findings without coronary angiography. While, in younger patients, TTS is generally a benign condition, in very elderly females, it is associated with higher in-hospital mortality and poor prognosis. Herein, we present four cases of ultra-octogenarian females diagnosed with "presumed TTS", who did not undergo coronary angiography due to severe frailty and multiple comorbidities and who exhibited poor outcome. This could arise the question if an early more aggressive approach could have changed final results. Probably, the solution could only be a personalized decision deriving from a profound and detailed discussion of each case through a multidisciplinary team approach.

Metabolic syndrome is related to vascular structural alterations but not to functional ones both in hypertensives and healthy subjects.

BACKGROUND AND AIMS: Metabolic Syndrome (MS) has been related to an impairment in arterial structural and functional properties with heterogeneous results. In this paper we focused on the effects of MS on arterial carotid-femoral PWV and common carotid IMT in two different populations, one of hypertensive patients and one of healthy controls. METHODS AND RESULTS: We enrolled 816 consecutive HT and 536 healthy controls. Vascular structural (IMT) and functional (PWV) properties were evaluated. NCEP-ATP-III criteria were used for diagnosis of MS. MS was diagnosed in 26.9% and 6.9% in hypertensive and control subjects, respectively. PWV was similar in controls with and without MS (7.7 ± 1.9 vs 7.6 ± 1.1 m/s, p = 0.69), while IMT was higher in controls with than those without MS (0.64 ± 0.18 vs 0.57 ± 0.13 mm, p = 0.02). Hypertensives with MS were older (57.9 ± 12.2 vs 52.7 ± 14.1 years, p < 0.001) and showed higher PWV (9.0 ± 2.3 vs 8.4 ± 2.1 m/s, p = 0.001) and IMT (0.72 ± 0.22 vs 0.65 ± 0.17 mm, p < 0.001) than those without MS, however at the age-adjusted analysis only the difference in IMT was confirmed (p = 0.007). Regression models showed that MS was an independent determinant of IMT in both controls (ß = 0.08, p = 0.03) and hypertensives (ß = 0.08, p = 0.01), but not of PWV either in controls (ß = 0.006, p = 0.886 and ß = 0.04, p = 0.19, respectively). CONCLUSIONS: the main finding of our work is that MS is a significant determinant of IMT while this is not the case for PWV. This result have been confirmed both in hypertensive subjects and in healthy controls.

Hyperuricemia prevalence in healthy subjects and its relationship with cardiovascular target organ damage.

BACKGROUND AND AIM: Heterogeneous results have been obtained in the relationship between Uric Acid (UA) and Target Organ Damage (TOD). In the present study we sought to assess the prevalence of hyperuricemia in healthy subjects as well as the role of UA in determining TOD. We evaluated vascular, cardiac and renal TODs in the whole population as well as sub-grouped by gender. METHODS AND RESULTS: As many as 379 blood donors participated at the present analysis. TOD was evaluated as Pulse Wave Velocity (PWV), Left Ventricular Mass Index (LVMI) and carotid Intima-Media Thickness (IMT). Hyperuricemia was defined with the classic cut-off (>7.0 in men and >6.0 mg/dL in women) but also with a most recently defined one (5.6 mg/dL for both sex). Hyperuricemia was present in 6.3% of the whole population (7.3% males, 2.8% females) considering the classic cut-off, while, with the recently identified one, it was present in 28.2% of the whole population (37.3% males, 4.7% females). Despite all the evaluated TODs significantly correlated with UA, linear multivariate regression analysis showed that none of them, except for GFR, displayed UA as a significant covariate. Similar figures were found also when both correlation and linear regression analyses were repeated in the two genders separately. CONCLUSIONS: Hyperuricemia is an important problem also in healthy subjects and its prevalence could further increase if lower cut-off will be used. In this specific population UA is significantly associated with renal impairment while this was not the case for cardiac and vascular damage.

Modified Haller Index is inversely associated with asymptomatic status in atrial fibrillation patients undergoing electrical cardioversion: a preliminary observation.

BACKGROUND: No previous study evaluated the possible influence of chest wall conformation on symptoms perception in atrial fibrillation (AF) patients candidates for electrical cardioversion (ECV). We aimed at evaluating the anthropometric and clinical characteristics of patients with persistent AF undergoing ECV, categorized according to the presence or absence of symptoms. METHODS: This study retrospectively analyzed a series of persistent AF patients scheduled for early ECV who underwent pre-procedural clinical evaluation, MHI (the ratio of chest transverse diameter over the distance between sternum and spine) assessment, transthoracic and transesophageal echocardiography implemented with strain analysis of both left atrium and left atrial appendage. Thromboembolic risk and burden of comorbidities were assessed by CHA2DS2-VASc Score and Charlson Comorbidity Index (CCI), respectively. The independent predictors of "asymptomatic AF" were assessed. RESULTS: A total of 25 asymptomatic and 90 symptomatic AF patients were retrospectively examined. Compared to symptomatic AF patients, those asymptomatic were significantly older (78.4±3.8 vs. 71.0±7.7 years, P<0.001), predominantly males (84 vs. 44.4%, P<0.001), with significantly lower MHI (2.0±0.1 vs. 2.4±0.1, P<0.001), higher CHA2DS2-VASc Score (5.8±1.1 vs. 3.6±1.1, P<0.001) and CCI (6.8±1.4 vs. 2.3±0.9, P<0.001), and greater impairment in biventricular systolic function and atrio-auricolar myocardial strain indices. On multivariate logistic regression analysis, CHA2DS2-VASc Score (OR=2.65, 95% CI: 1.53-4.60) and CCI (OR=2.36, 95% CI: 1.16-4.66) were linearly associated with the endpoint "asymptomatic AF," whereas MHI (OR 0.76, 95% CI 0.59-0.97) was inversely associated with the asymptomatic status. A MHI <2.2 was the best cut-off for detecting asymptomatic AF patients. CONCLUSIONS: MHI is inversely associated with asymptomatic status in persistent AF patients undergoing ECV. MHI assessment might represent an innovative practical approach to AF patients.

Influence of gestational diabetes mellitus on subclinical myocardial dysfunction during pregnancy: A systematic review and meta-analysis.

OBJECTIVE: The correlation between gestational diabetes mellitus (GDM) and subclinical myocardial dysfunction has been poorly investigated. Accordingly, we performed a meta-analysis to examine the influence of GDM on left ventricular (LV) global longitudinal strain (GLS), assessed by speckle tracking echocardiography (STE), during pregnancy. STUDY DESIGN: All echocardiographic studies assessing conventional echoDoppler parameters and LV-GLS in GDM women vs. healthy controls, selected from PubMed and EMBASE databases, were included. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment of Case-Control Studies. The subtotal and overall standardized mean differences (SMDs) of LV-GLS were calculated using the random-effect model. RESULTS: The full-texts of 10 studies with 1147 women with GDM and 7706 pregnant women without diabetes were analyzed. GDM women enrolled in the included studies were diagnosed with a small reduction in LV-GLS in comparison to controls (average value -19.4 ± 2.5 vs -21.8 ± 2.5 %, P < 0.001) and to the accepted reference values (more negative than -20 %). Substantial heterogeneity was detected for the included studies, with an overall statistic value I2 of 94.4 % (P < 0.001). Large SMDs were obtained for the included studies, with an overall SMD of -0.97 (95 %CI -1.32, -0.63, P < 0.001). Egger's test for a regression intercept gave a P-value of 0.99, indicating no publication bias. On meta-regression analysis, all moderators and/or potential confounders (age at pregnancy, BMI, systolic blood pressure and ethnicity) were not significantly associated with effect modification (all P < 0.05). CONCLUSIONS: GDM is independently associated with subclinical myocardial dysfunction in pregnancy. STE analysis allows to identify, among GDM women, those who might benefit of targeted non-pharmacological and/or pharmacological interventions, aimed at reducing the risk of developing type 2 diabetes and cardiovascular complications later in life.

An unusual right atrial myxoma triggering presumed takotsubo syndrome in a 97-year-old female.

A 97-year-old female was admitted to the emergency department of our hospital due to paroxysmal nocturnal dyspnea and chest pain. At the hospital admission, the patient manifested transient psychomotor agitation and dysarthria. On physical examination, blood pressure was 115/60 mmHg and pulse 96 b.p.m. On blood tests, troponine I was 0.08 ng/mL (normal range <0.04 ng/mL). Electrocardiography (ECG) showed sinus rhythm and ST segment elevation in both inferior and anterior leads except in lead V1. Transthoracic echocardiography (TTE) revealed a right atrial multilobulated, hypermobile, echogenic cauliflower mass (maximum size of 5 cm × 4 cm), which was attached to the tricuspid lateral annulus with a short stalk (Figure 1A). The right atrial mass, which had filiform extremities and was found to prolapse through the tricuspid valve into the right ventricle, was ascribed to a peduncolated myxoma. Its motion was very rapid and uncoordinated, with increased peak antegrade velocity (Vmax = 35 cm/s), as precisely measured by pulsed wave tissue Doppler imaging (PW-TDI) (Figure 1B). Estimated left ventricular ejection fraction (LVEF) was normal (60%), and no significant valvulopathy was detected. Finally, a bulging of the interatrial septum with right-to-left shunt, through a patent foramen ovale (PFO), was observed by using colour Doppler (Figure 1C). Acute ischaemic lesions were excluded by brain computed tomography scan.

Comparison of clinical scoring to predict mortality risk in mild-to-moderate idiopathic pulmonary fibrosis.

BACKGROUND: During the last decade, a number of clinical scores, such as Gender-Age-Physiology (GAP) Index, TORVAN Score and Charlson Comorbidity Index (CCI), have been separately used to measure comorbidity burden in idiopathic pulmonary fibrosis (IPF). However, no previous study compared the prognostic value of these scores to assess mortality risk stratification in IPF patients with mild-to-moderate disease. METHODS: All consecutive patients with mild-to-moderate IPF who underwent high-resolution computed tomography, spirometry, transthoracic echocardiography and carotid ultrasonography at our Institution, between January 2016 and December 2018, were retrospectively analyzed. GAP Index, TORVAN Score and CCI were calculated in all patients. Primary endpoint was all-cause mortality, whereas secondary endpoint was the composite of all-cause mortality and rehospitalizations for all-causes, over medium-term follow-up. RESULTS: Seventy IPF patients (70.2±7.4 yrs, 74.3% males) were examined. At baseline, GAP Index, TORVAN Score and CCI were 3.4±1.1, 14.7±4.1 and 5.3±2.4, respectively. A strong correlation between coronary artery calcification (CAC) and common carotid artery (CCA) intima-media thickness (IMT) (r=0.88), CCI and CAC (r=0.80), CCI and CCA-IMT (r=0.81), was demonstrated in the study group. Follow-up period was 3.5±1.2 years. During follow-up, 19 patients died and 32 rehospitalizations were detected. CCI (HR 2.39, 95% CI: 1.31-4.35) and heart rate (HR 1.10, 95% CI: 1.04-1.17) were independently associated with primary endpoint. CCI (HR 1.54, 95% CI: 1.15-2.06) predicted secondary endpoint, also. A CCI ≥6 was the optimal cut-off for predicting both outcomes. CONCLUSIONS: Due to the increased atherosclerotic and comorbidity burden, IPF patients with CCI ≥6 at an early-stage disease have poor outcome over medium-term follow-up.

The influence of pectus excavatum on cardiac kinetics and function in otherwise healthy individuals: A systematic review.

BACKGROUND: A number of anterior chest wall deformities, most notably pectus excavatum (PE), may have a detrimental effect on cardiac motion and function. Interpretation of transthoracic echocardiography (TTE) and speckle-tracking echocardiography (STE) results may be hampered by the possible influence of PE on cardiac kinetics. METHODS: A comprehensive search of all articles assessing cardiac function in PE individuals was carried out. Inclusion criteria were: 1) individuals aged >10 years; 2) studies providing objective assessment of chest deformity (Haller index). Studies that measured myocardial strain parameters in PE patients were also included. RESULTS: The search (EMBASE and Medline) yielded a total of 392 studies, 36 (9.2%) of which removed as duplicates; a further 339 did not meet inclusion criteria. The full-texts of 17 studies were then analyzed. All studies concordantly reported impaired right ventricular volumes and function. With respect to left ventricle (LV), TTE studies uniformly demonstrated a significant impairment in conventional echoDoppler indices in PE individuals, whereas STE studies provided conflicting results. Importantly, LV functional alterations promptly reverted upon surgical correction of chest defect. In subjects with PE of mild-to-moderate severity, we observed that degree of anterior chest wall deformity, as noninvasively assessed by modified Haller index (MHI), was strongly associated with myocardial strain magnitude, in heterogenous cohorts of otherwise healthy PE individuals. CONCLUSIONS: Clinicians should be aware that in PE individuals, TTE and STE results may not always be indicative of intrinsic myocardial dysfunction, but may be, at least in part, influenced by artifactual and/or external chest shape determinants.

An Unusual Case of Ascending Aorta Dissection 4 Years after Perceval Sutureless Bioprosthesis Implantation: Easier Access to Diagnosis through the Right Parasternal Longitudinal Echocardiographic Window.

Sutureless bioprostheses are more frequently used for the surgical treatment of elderly patients with high burden of comorbidity, who are candidates to aortic valve replacement (AVR). Among the sutureless bioprostheses, the Perceval valve has shown a good midterm durability, with very few reports of valve deterioration and low risk of complications. Herein, we present an unusual case of ascending aorta dissection which occurred 4 years after AVR with a Perceval sutureless pericardial bioprosthesis, likely related to the peculiar prosthetic design. A high right parasternal longitudinal view of the aorta in the right lateral decubitus allowed to suspect the acute aortic syndrome, thus accelerating the subsequent diagnostic and therapeutic iter.

Nutraceuticals in Chronic Coronary Syndromes: Preclinical Data and Translational Experiences.

Non-pharmacological treatments have always been considered important in the management of Chronic Coronary Syndromes. Nutraceuticals ("Nutrition" + "Pharmaceutical") could fall both under the definition of non-pharmacological treatment and pharmacological one or, probably more correctly, in the middle of these two kinds of therapies. However, the word "nutraceuticals" never appears in the latest guidelines on this issue. This is probably determined by the fact that evidences on this topic are scarce and most of the published articles are based on preclinical data while translational experiences are available only for some molecules. In this review we will focus on nutraceutical strategies that act on the ischemic myocardium itself and not only on the cardiovascular risk factors. As demonstrated by the important number of papers published in recent years, this is an evolving topic and evaluated substances principally act on two mechanisms (cardiac energetics and ischemia-reperfusion damage) that will be also reviewed.

Covid and Cardiovascular Diseases: Direct and Indirect Damages and Future Perspective.

SARS-CoV-2 infection determines a disease that predominantly affects lungs. However the cytokines storms, determined by the huge immune response to the infection, could affect also other organs and apparatus such as heart and vessels. Beyond the acute inflammation itself also hypercoagulative status has been linked to SARSCoV-2 infection and this surely relates to the increase seen in prevalence of pulmonary embolism and myocardial infarction. A number of cardiac abnormalities and pathologies have been observed, with special attention to cardiac arrhythmias and myocardial involvement. Furthermore, indirect damages determined by the reduction in acute and chronic cardiovascular care, results in a strong mortality and morbidity outcomes in cardiological patients. In this review we will summarise current knowledge on both direct and indirect cardiovascular damages determined by the SARS-CoV-2 pandemia.

Heart Rate in Patients with SARS-CoV-2 Infection: Prevalence of High Values at Discharge and Relationship with Disease Severity.

The most common arrhythmia associated with COronaVIrus-related Disease (COVID) infection is sinus tachycardia. It is not known if high Heart Rate (HR) in COVID is simply a marker of higher systemic response to sepsis or if its persistence could be related to a long-term autonomic dysfunction. The aim of our work is to assess the prevalence of elevated HR at discharge in patients hospitalized for COVID-19 and to evaluate the variables associated with it. We enrolled 697 cases of SARS-CoV2 infection admitted in our hospital after February 21 and discharged within 23 July 2020. We collected data on clinical history, vital signs, laboratory tests and pharmacological treatment. Severe disease was defined as the need for Intensive Care Unit (ICU) admission and/or mechanical ventilation. Median age was 59 years (first-third quartile 49, 74), and male was the prevalent gender (60.1%). 84.6% of the subjects showed a SARS-CoV-2 related pneumonia, and 13.2% resulted in a severe disease. Mean HR at admission was 90 ± 18 bpm with a mean decrease of 10 bpm to discharge. Only 5.5% of subjects presented HR > 100 bpm at discharge. Significant predictors of discharge HR at multiple linear model were admission HR (mean increase = ß = 0.17 per bpm, 95% CI 0.11; 0.22, p < 0.001), haemoglobin (ß = -0.64 per g/dL, 95% CI -1.19; -0.09, p = 0.023) and severe disease (ß = 8.42, 95% CI 5.39; 11.45, p < 0.001). High HR at discharge in COVID-19 patients is not such a frequent consequence, but when it occurs it seems strongly related to a severe course of the disease.

Nontraumatic headaches in the emergency department: evaluation of a clinical pathway.

OBJECTIVE: To determine the impact and efficacy of a clinical pathway in the management of patients with nontraumatic and afebrile headache (NTAH) in the emergency department (ED). BACKGROUND: Nontraumatic and afebrile headache is one of the most common neurological symptoms in the ED. However, data about the application of an evidence-based operative protocol are lacking. METHODS: A before-after intervention study comparing adult patients presenting to the ED with atraumatic headache was conducted during a 6-month period from April to September 2005 and with the same type of patients in the same period in 2006 after a clinical pathway had been implemented. According to their clinical presentations, patients of the 2006 group were divided into 3 subgroups and managed following the established protocol. Study results were based on analysis of 6 months of clinical outcome, the number of CT head scans in the ED, number of neurological consultations in the ED, number of admissions, and length of stay in the ED. RESULTS: A total of 686 patients were enrolled in the study, of which 374 were those presenting to our ED with NTAH in 2006 and managed with the aid of the study protocol; the other 312 patients were those who presented in 2005, before the intervention. The study protocol was strictly applied to 247 patients (66%) of the 2006 group. There were fewer neurological consultations after the intervention (41.2% vs 52.5%, difference: -11.3%, 95% confidence intervals [CI]: -18.7% to -3.9%; P = .003); likewise, admissions were significantly reduced after the intervention (9.0% vs 14.7%, difference: -5.7%, 95% CI: -10.6% to -0.8%; P = .02). No significant differences were found between the 2 groups for number of CT head scans (42.2% vs 38.4%, difference: 3.7%, 95% CI: -3.5% to 11%; P = .3). Mean length of stay in the ED was lower after the intervention, though not significantly (170.6 +/- 102 minutes vs 180.5 +/- 105 minutes, difference: -9.8 minutes, 95% CI: -20.3 to 5.7; P = .09). A 6-month follow-up was completed involving 302 (96.7%) patients in the first group and 370 (98.9%) in the second group. There was only one misdiagnosis after the intervention while 2 incorrect diagnoses were made before the intervention (0.27% vs 0.6%, difference: -0.33%, 95% CI: -2.1% to 0.9%; P = .5). CONCLUSIONS: Our diagnostic protocol for NTAH appears to be safe and sensitive in diagnosing malignant headaches. In addition, it may improve use of resources by reducing the need for neurological consultations and admissions without increasing the number of CT scans or prolonging length of stay in the ED. Furthermore, when using the protocol ED physicians seem more confident in their evaluations of headache resulting in fewer requests for specialist input.

Vascular Aging and Disease of the Large Vessels: Role of Inflammation.

Structural and functional arterial properties commonly impair with aging process. These effects on vasculature could act at many levels from microcirculation to large vessels. Above normal aging process classic cardio-vascular risk factors (hypertension, diabetes mellitus, dyslipidemia, etc.) accelerate the physiological process leading to premature structural and functional alterations that has also been termed early vascular aging. Target organ damage evaluation could be clinically important since these alterations precede by many years' cardiovascular events and so their assessment can predict the onset of more serious and costly events giving the opportunity to prevent CV events by earlier therapeutic intervention. This review will focus on large artery functional properties and particularly on the role of inflammation on the aortic stiffening process.

Physiologic modulation of natural killer cell activity as an index of Alzheimer's disease progression.

Patients with Alzheimer's disease (AD) are characterized by an altered sensitivity to cortisol-mediated modulation of circulating lymphocytes. Longitudinal studies are needed to address the clinical applicability of these abnormalities as prognostic factors. Therefore, we designed a longitudinal study to address the clinical applicability of physiologic modulation of Natural Killer (NK) cell activity as a prognostic factor in AD. NK activity was assessed as baseline measurement and in response to modulation by cortisol at 10(-6)M. To verify the immunophysiological integrity of the NK cell population, we tested augmentation of NK cytotoxicity by human recombinant interleukin (IL)-2 (100 IU/ml) as control. The response to modulation by cortisol or by IL-2 was significantly greater in patients with AD. Based on change in the Mini-Mental State score at entry and at 18 months, patients with AD could be assigned to a "fast progression" (Delta > 2 points) or to a "slow progression" group (Delta

Aluminium blunts the proliferative response and increases apoptosis of cultured human cells: putative relationship to Alzheimer's disease.

Aluminium (Al) has been investigated as a neurotoxic substance. Al ranks among the potential environmental risk factors for Alzheimer's disease (AD). Epidemiological studies tested the relationship between Al in drinking water and AD, showing a significant correlation between elevated levels of monomeric Al in water and AD, although data to date remain inconclusive with respect to total Al. The aim of this study was to test whether or not Al exacerbates cellular toxicity mediated by the amyloid beta (Abeta) peptide. We evaluated the role of Al in modulating programmed cell death (apoptosis) in human cell cultures. We used the osteosarcoma cell line monolayer (SaOs-2) to demonstrate that treatment of SaOs-2 cultures with the Abeta peptide mid-fragment (25 to 35) at nano M, followed by co-incubation with physiological concentrations of aluminium chloride, which release monomeric Al in solution, led to marked expression of caspase 3, but not caspase 9, key markers of the apoptotic process. The same experimental conditions were shown to blunt significantly the proliferative response of normal human peripheral blood mononuclear cells (PBMC) to phytohemagglutinin (PHA) stimulation. Our observations support the hypothesis that Al significantly impairs certain cellular immune responses, and confirm that Al-mediated cell toxicity may play an important role in AD.

Neuroendocrine immunity in patients with Alzheimer's disease: toward translational epigenetics.

The emerging domain of epigenetics in molecular medicine finds application for a variety of patient populations. Here, we present fundamental neuroendocrine immune evidence obtained in patients with senile dementia of the Alzheimer's type (sDAT), and discuss the implications of these data from the viewpoint of translational epigenetics of Alzheimer's disease. We followed 18 subjects with mild sDAT treated with acetylcholinesterase inhibitors, and 10 control subjects matched for age in a repeated measure design every six months for 18 months. We monitored psychosocial profile (Mini-Mental State Examination, Functional Assessment Staging, Independence in Activities of Daily Living, Depression, Profile of Moods States) in parallel to immunophenotypic parameters of T cell subpopulations by flow cytometry. Based on change in the mini-mental state score at entry and at 18 months, patients with sDAT were assigned to a "fast progression" (delta greater than 2 points) or to a "slow progression" group (delta less than or equal to 2 points). The change in circulating activated T cells (CD3+Dr+) with time in patients with sDAT was significantly inversely correlated with the change in time in natural killer (NK) cytotoxic activity to cortisol modulation in these patients, which was greater in patients with fast progression, compared to slow progression sDAT. These data indicate underlying neuroendocrine immune processes during progression of sDAT. Our observations suggest that psychoimmune measures such as those we have monitored in this study provide relevant information about the evolving physiological modulation in patients with sDAT during progression of Alzheimer's disease, and point to new or improved translational epigenetic treatment interventions.

Systemic autonomic involvement in episodic cluster headache: a comparison between active and remission periods.

In this study we compared systemic autonomic involvement in episodic cluster headache during active and silent periods. Seventeen patients were studied with sympathetic skin response, lying to standing test, Valsalva manoeuvre, deep breathing test and orthostatic hypotension evaluation. Each of them underwent these tests during active and silent periods. Values were then compared with normal controls. Our data show a parasympathetic, but not sympathetic, involvement. Moreover, this impairment seems to be "chronic", as it persists beyond the active period.