Clinical Phenotypes and Prognosis of Dilated Cardiomyopathy Caused by Truncating Variants in the <i>TTN</i> Gene

Background: Truncating variants in the TTN gene (TTNtv) are the commonest cause of heritable dilated cardiomyopathy. This study aimed to study the phenotypes and outcomes of TTNtv carriers. Methods: Five hundred thirty-seven individuals (61% men; 317 probands) with TTNtv were recruited in 14 centers (372 [69%] with baseline left ventricular systolic dysfunction [LVSD]). Baseline and longitudinal clinical data were obtained. The primary end point was a composite of malignant ventricular arrhythmia and end-stage heart failure. The secondary end point was left ventricular reverse remodeling (left ventricular ejection fraction increase by ≥10% or normalization to ≥50%). Results: Median follow-up was 49 (18–105) months. Men developed LVSD more frequently and earlier than women (45±14 versus 49±16 years, respectively; P =0.04). By final evaluation, 31%, 45%, and 56% had atrial fibrillation, frequent ventricular ectopy, and nonsustained ventricular tachycardia, respectively. Seventy-six (14.2%) individuals reached the primary end point (52 [68%] end-stage heart failure events, 24 [32%] malignant ventricular arrhythmia events). Malignant ventricular arrhythmia end points most commonly occurred in patients with severe LVSD. Male sex (hazard ratio, 1.89 [95% CI, 1.04–3.44]; P =0.04) and left ventricular ejection fraction (per 10% decrement from left ventricular ejection fraction, 50%; hazard ratio, 1.63 [95% CI, 1.30–2.04]; P &lt;0.001) were independent predictors of the primary end point. Two hundred seven of 300 (69%) patients with LVSD had evidence of left ventricular reverse remodeling. In a subgroup of 29 of 74 (39%) patients with initial left ventricular reverse remodeling, there was a subsequent left ventricular ejection fraction decrement. TTNtv location was not associated with statistically significant differences in baseline clinical characteristics, left ventricular reverse remodeling, or outcomes on multivariable analysis ( P =0.07). Conclusions: TTNtv is characterized by frequent arrhythmia, but malignant ventricular arrhythmias are most commonly associated with severe LVSD. Male sex and LVSD are independent predictors of outcomes. Mutation location does not impact clinical phenotype or outcomes. </jats:sec

Prophylactic heparin and risk of orotracheal intubation or death in patients with mild or moderate COVID-19 pneumonia

AbstractProphylactic low molecular weight heparin (pLMWH) is currently recommended in COVID-19 to reduce the risk of coagulopathy. The aim of this study was to evaluate whether the antinflammatory effects of pLMWH could translate in lower rate of clinical progression in patients with COVID-19 pneumonia. Patients admitted to a COVID-hospital in Rome with SARS-CoV-2 infection and mild/moderate pneumonia were retrospectively evaluated. The primary endpoint was the time from hospital admission to orotracheal intubation/death (OTI/death). A total of 449 patients were included: 39% female, median age 63 (IQR, 50–77) years. The estimated probability of OTI/death for patients receiving pLMWH was: 9.5% (95% CI 3.2–26.4) by day 20 in those not receiving pLMWH vs. 10.4% (6.7–15.9) in those exposed to pLMWH; p-value = 0.144. This risk associated with the use of pLMWH appeared to vary by PaO2/FiO2 ratio: aHR 1.40 (95% CI 0.51–3.79) for patients with an admission PaO2/FiO2 ≤ 300 mmHg and 0.27 (0.03–2.18) for those with PaO2/FiO2 &gt; 300 mmHg; p-value at interaction test 0.16. pLMWH does not seem to reduce the risk of OTI/death mild/moderate COVID-19 pneumonia, especially when respiratory function had already significantly deteriorated. Data from clinical trials comparing the effect of prophylactic vs. therapeutic dosage of LMWH at various stages of COVID-19 disease are needed.</jats:p

Neuropsychological tests at the Italian Centers for Cognitive Disorders and Dementias: results from a survey on 450 specialized services

Background: The Italian Fund for Alzheimer’s and other dementias approved in 2020 enabled the conducting of a survey in the&nbsp;Italian Centers for Cognitive Disorders and Dementias (CCDDs) to analyse the organization, the administrative features and the professionals’ characteristics. Aims: To investigate the current use of neuropsychological (NP) tests in Italian CCDDs and the association between the use of a basic set of tests for neuropsychological assessment (NPA) and organizational/structural characteristics of CCDDs. Methods: A survey was conducted with an online questionnaire in all CCDDs between July 2022 and February 2023. To verify the use of a comprehensive NPA in the diagnosis of cognitive disorders and dementia, we identified a minimum core test (MCT). Results: The CCDDs using a Minimum Core Test (MCT) significantly increased from 45.7% in 2015 to the current 57.1%. Territorial CCDDs using MCT significantly increased from 24.9% in 2015 to 37% in 2022 (p = 0.004). As multivariable results, the presence of psychologist/neuropsychologist in the staff and the University-based/IRCCS CCDDs increased the probability of using MCT (OR = 9.2; 95%&nbsp;CI 5.6–15.0; p &lt; 0.001 and OR = 5.4; 95%&nbsp;CI 1.9–15.9; p = 0.002, respectively), while CCDDs in Southern Italy-Islands showed a lower probability than those in the North (OR = 0.4; 95%&nbsp;CI 0.2–0.7; p = 0.001). Discussion: Almost half of CCDDs (43%) do not use MCT in their clinical practice. The presence of the psychologist/neuropsychologist on the staff has a key role in the adoption of MCT and regional differences have increased over the past years. NPA is crucial in the diagnostic process and in characterizing risk profiles in order to implement targeted interventions for risk reduction. Conclusions: Our results could help to identify good practices aimed at improving dementia diagnosis. An intervention by health policymakers is urgently needed with the aim of improving diagnostic appropriateness and overcoming regional differences

The Profile of the Italian Centers for Cognitive Disorders and Dementia in the Context of New Drugs in Alzheimer’s Disease

Background: The wait for the upcoming disease-modifying therapies (DMT) for Alzheimer’s disease in Europe is raising questions about the preparedness of national healthcare systems to conduct accurate diagnoses and effective prescriptions. In this article, we focus on the current situation in Italy. Objective: The primary goal is to propose a profile of the Italian Centers for Cognitive Disorders and Dementias (CCDDs) that could be taken into consideration by regional and autonomous provincial authorities when deciding on the prescribing centers for DMT. Methods: Based on responses to a national survey on CCDDs in Italy, we identified the CCDDs that meet the requirements for effective prescription: 1) Multidisciplinary team; 2) Minimum Core Test for the neuropsychological assessment; 3) PET, CSF, and Brain MRI assessments. Univariate and multivariate comparisons were conducted between CCDDs that met the criteria and the others. Results: Only 10.4% of CCDDs met the requirements for effective DMT prescription, mainly located in Northern Italy. They are also characterized by longer opening hours, a higher number of professionals, a university location, and a higher frequency of conducting genetic tests, and could potentially result in prescribing centers. Conclusions: The findings suggest that the Italian national healthcare system may benefit from further enhancements to facilitate the effective prescription of DMTs. This could involve initiatives to reduce fragmentation, ensure adequate resources and equipment, and secure sufficient funding to support this aspect of healthcare delivery

A new national survey of centers for cognitive disorders and dementias in italy

Introduction: A new national survey has been carried out by the Italian Centers for Cognitive Disorders and Dementias (CCDDs). The aim of this new national survey is to provide a comprehensive description of the characteristics, organizational aspects of the CCDDs, and experiences during the COVID-19 pandemic. Methods: A list of all national CCDDs was requested from the delegates of each Italian region. The online questionnaire is divided in two main sections: a profile section, containing information on location and accessibility, and a data collection form covering organization, services, treatments, activities, and any service interruptions caused by the COVID-19 outbreak. Results: In total, 511 out of 534 (96%) facilities completed the profile section, while 450 out of 534 (84%) CCDDs also completed the data collection form. Almost half of the CCDDs (55.1%) operated for 3 or fewer days a week. About one-third of the facilities had at least two professional figures among neurologists, geriatricians and psychiatrists. In 2020, only a third of facilities were open all the time, but in 2021, two-thirds of the facilities were open. Conclusion: This paper provides an update on the current status of CCDDs in Italy, which still shows considerable heterogeneity. The survey revealed a modest improvement in the functioning of CCDDs, although substantial efforts are still required to ensure the diagnosis and care of patients with dementia