Dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes: the DAPAHEART Trial: a preliminary report.

OBJECTIVE: Cardiovascular (CV) outcome trials have shown that in patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduces CV mortality and hospital admission rates for heart failure (HF). However, the mechanisms behind these benefits are not fully understood. This study was performed to investigate the effects of the SGLT-2i dapagliflozin on myocardial perfusion and glucose metabolism in patients with T2D and stable coronary artery disease (coronary stenosis ≥ 30% and < 80%), with or without previous percutaneous coronary intervention (> 6 months) but no HF. METHODS: This was a single-center, prospective, randomized, double-blind, controlled clinical trial including 16 patients with T2D randomized to SGLT-2i dapagliflozin (10 mg daily) or placebo. The primary outcome was to detect changes in myocardial glucose uptake (MGU) from baseline to 4 weeks after treatment initiation by [(18)F]2-deoxy-2-fluoro-D-glucose (FDG) PET/CT during hyperinsulinemic euglycemic clamp. The main secondary outcome was to assess whether the hypothetical changes in MGU were associated with changes in myocardial blood flow (MBF) and myocardial flow reserve (MFR) measured by 13N-ammonia PET/CT. The study was registered at eudract.ema.europa.eu (EudraCT No. 2016-003614-27) and ClinicalTrials.gov (NCT03313752). RESULTS: 16 patients were randomized to dapagliflozin (n = 8) or placebo (n = 8). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). There was no significant change in MGU during euglycemic hyperinsulinemic clamp in the dapagliflozin group (2.22 ± 0.59 vs 1.92 ± 0.42 µmol/100 g/min, p = 0.41) compared with the placebo group (2.00 ± 0.55 vs 1.60 ± 0.45 µmol/100 g/min, p = 0.5). Dapagliflozin significantly improved MFR (2.56 ± 0.26 vs 3.59 ± 0.35 p = 0.006 compared with the placebo group 2.34 ± 0.21 vs 2.38 ± 0.24 p = 0.81; pint = 0.001) associated with a reduction in resting MBF corrected for cardiac workload (p = 0.005; pint = 0.045). A trend toward an increase in stress MBF was also detected (p = 0.054). CONCLUSIONS: SGLT-2 inhibition increases MFR in T2D patients. We provide new insight into SGLT-2i CV benefits, as our data show that patients on SGLT-2i are more resistant to the detrimental effects of obstructive coronary atherosclerosis due to increased MFR, probably caused by an improvement in coronary microvascular dysfunction. Trial registration EudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752.

Quarantine during COVID-19 outbreak: Changes in diet and physical activity increase the risk of cardiovascular disease.

AIMS: CoV-19/SARS-CoV-2 is a highly pathogenic virus that is causing a global pandemic with a high number of deaths and infected people. To contain the diffusion of infection, several governments have enforced restrictions on outdoor activities or even collective quarantine on the population. The present commentary briefly analyzes the effects of quarantine on lifestyle, including nutrition and physical activity and the impact of new technologies in dealing with this situation. DATA SYNTHESIS: Quarantine is associated with stress and depression leading to unhealthy diet and reduced physical activity. A diet poor in fruit and vegetables is frequent during isolation, with a consequent low intake of antioxidants and vitamins. However, vitamins have recently been identified as a principal weapon in the fight against the Cov-19 virus. Some reports suggest that Vitamin D could exert a protective effect on such infection. During quarantine, strategies to further increase home-based physical activity and to encourage adherence to a healthy diet should be implemented. The WHO has just released guidance for people in self-quarantine, those without any symptoms or diagnosis of acute respiratory illness, which provides practical advice on how to stay active and reduce sedentary behavior while at home. CONCLUSION: Quarantine carries some long-term effects on cardiovascular disease, mainly related to unhealthy lifestyle and anxiety. Following quarantine, a global action supporting healthy diet and physical activity is mandatory to encourage people to return to a good lifestyle routine.

A pandemic of delirium: an updated systematic review and meta-analysis of occurrence of delirium in older adults with COVID-19.

PURPOSE: Delirium has been recognized as an atypical presenting feature of COVID-19 in older adults and is independently associated with mortality. We aimed to perform an updated systematic review of the literature and proportional meta-analysis to assess prevalence and incidence of delirium in older adults with COVID-19, addressing differences according to sex, frailty status, and settings. METHODS: We searched databases for English-language articles on prevalence and incidence of delirium in older adults with COVID-19, published between March 2020 and January 2023. RESULTS: Of the 1171 articles identified, 66 met selection criteria and were included in the meta-analysis (n = 35,035 participants, age-range 66-90 years old, 46.6% females). We observed similar pooled prevalence (20.6% [95% Confidence Interval (CI) 17.8-23.8%]) and incidence (21.3% [95% CI 14.7-30%]) of delirium. Pooled occurrence (both prevalence and incidence) of delirium was similar according to sex (females 21.3% [95% CI 16-27.5%] vs. males 23.8%% [95% CI 18.2-30.4%], p-value = 0.55) and study setting (nursing homes 22.5% [95% CI 14.2-33.6%] vs. hospital 20.3% [95% CI 17-24%], p = 0.68), but it was significantly higher in frail versus non-frail patients (37% [95% CI 26.6-48.8%] vs. 12.5% [95% CI 7.8-19.6%], p-value < 0.01). Delirium definitions and assessment tools largely varied across studies. CONCLUSION: This review delineates delirium as a common feature of COVID-19, particularly in frail older adults, and supports its formal inclusion among COVID-19 symptoms. The considerable heterogeneity in delirium assessment highlights the need for an operational strategy to standardize definitions and tools utilization in the management of frail older adults.

Climate change versus Mediterranean diet: A hazardous struggle for the women's heart.

Climate change impacts food systems, causing nutritional deficiencies and increasing cardiovascular diseases (CVD). Regulatory frameworks like the European Farm-to-Fork Strategy aim to mitigate these effects, but current EU food safety regulations inadequately address health risks from poor diet quality and contaminants. Climate change adversely affects food quality, such as nutrient depletion in crops due to higher CO2 levels, leading to diets that promote chronic diseases, including CVD. Women, because of their roles in food production and their unique physiological responses to nutrients, face distinct vulnerabilities. This review explores the interplay between climate change, diet, and cardiovascular health in women. The review highlights that sustainable diets, particularly the Mediterranean diet, offer health benefits and lower environmental impacts but are threatened by climate change-induced disruptions. Women's adherence to the Mediterranean diet is linked to significant reductions in CVD risk, though sex-specific responses need further research. Resilient agricultural practices, efficient water management, and climate-smart farming are essential to mitigate climate change's negative impacts on food security. Socio-cultural factors influencing women's dietary habits, such as traditional roles and societal pressures, further complicate the picture. Effective interventions must be tailored to women, emphasizing education, community support, policy changes, and media campaigns promoting healthy eating. Collaborative approaches involving policymakers, health professionals, and the agricultural sector are crucial for developing solutions that protect public health and promote sustainability. Addressing the multifaceted challenges posed by climate change to food quality and cardiovascular health in women underscores the need for integrated strategies that ensure food security, enhance diet quality, and mitigate environmental impacts.

How to conduct research in palliative care? A perspective from Italy.

BACKGROUND: In western countries, the increasing life expectancy and the growing number of individuals with advanced chronic conditions have resulted in a greater demand for palliative care. Specifically, Italy has witnessed substantial growth in the palliative care field, marked by the establishment of Palliative Care Networks and an academic fellowship program in 2022. To further enhance this field, it is crucial to conduct high-quality scientific research that produces results applicable in clinical practice. AIM: This article explores challenges and potential solutions in conducting effective palliative care research, considering sample definition, research settings, outcomes, and ethical concerns. While focusing on the Italian context, the presented research framework can be applied to other contexts and regions. RESULTS: Palliative care research is complex and challenging due to its holistic approach, which encompasses various vital dimensions of patients and their families, including physical, emotional, and social needs. The Italian and worldwide experience provides insights into managing these challenges and enhancing the methodological rigor of studies and the practical application of research findings. CONCLUSIONS: This article emphasizes the importance of developing protocols tailored to palliative care's unique characteristics, and the necessity of dedicated funding for palliative care research, calling for increased support and recognition. The article advocates for improvement of the quality and relevance of palliative care studies, promoting better patient outcomes and enhanced caregiving.

Atypical Presentation of Pill Aspiration in Older Adults with Dysphagia: A Picture Not To Be Forgotten.

Nonconventional clinical presentations of diseases are common in older adults. Even dramatic events, such as foreign body (FB) inhalation, can occur in a subtle and non-specific manner. Pill aspiration is a rare yet overlooked cause of airway injury. It accounts for approximately 7% of all FB aspirations. In contrast, oral dysphagia and polypharmacology, mainly administrated in solid oral dosage forms (SDOF), like tablets and pills, are common conditions in older adults. Herein, we present a case of SDOF aspiration in a 78-year-old man. FB inhalation developed with general clinical deterioration and neurological impairment (delirium) rather than overt respiratory symptoms. Bronchoscopy provided remarkable images of this unexpected finding. Caregivers and healthcare workers must be aware of the risk of SDOF aspiration and adopt proper safety measures. Early recognition and bronchoscopy for diagnostic and therapeutic purposes can be lifesaving in such cases.

Cardiovascular disease prevention and therapy in women with Type 2 diabetes.

Cardiovascular disease (CVD) is the leading cause of death among men and women, although women are usually underdiagnosed and experience a delay in diagnosis. This also occurs in women with type 2 diabetes mellitus, despite the fact that diabetes is recognized as a major cardiovascular risk factor. Several factors influence the gap between diagnosis and treatment of cardiovascular disease in women: lack of perception of cardiovascular risk, effects of sex-related risk factors and the action of drugs in women. Women with Type 2 diabetes mellitus are more likely to be assigned a lower CVD risk category and to receive lifestyle counseling as well as less intensive CVD therapy compared with men. The present narrative review aims to analyze the risk of CVD in women with Type 2 diabetes mellitus and whether there is a difference between men and women in the efficacy of SGLT-2 inhibitors, new hypoglycemic drugs.

Lay abstract Despite the fact that cardiovascular disease is the most frequent cause of death in women in industrialized countries, the idea that it affects mainly men and affects women only after menopause still persists. This results in underdiagnosis and undertreatment of cardiovascular disease in women. This phenomenon depends on various factors, including lack of perception of risk in women themselves, reduced social action regarding prevention of cardiovascular disease risk factors in women and lower presence of women in the populations included in scientific studies. The condition is also present in women with Type 2 diabetes mellitus, who have a high risk of developing cardiovascular disease even before menopause. This review is aimed at exploring the factors that determine an underestimation of cardiovascular risk in women with Type 2 diabetes mellitus. Failure to identify risk carries a high social and economic cost.

Effect of Dapagliflozin on Myocardial Insulin Sensitivity and Perfusion: Rationale and Design of The DAPAHEART Trial.

INTRODUCTION: Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been shown to have beneficial effects on various cardiovascular (CV) outcomes in patients with type 2 diabetes (T2D) in primary prevention and in those with a high CV risk profile. However, the mechanism(s) responsible for these CV benefits remain elusive and unexplained. The aim of the DAPAHEART study will be to demonstrate that treatment with SGLT-2 inhibitors is associated with greater myocardial insulin sensitivity in patients with T2D, and to determine whether this improvement can be attributed to a decrease in whole-body (and tissue-specific) insulin resistance and to increased myocardial perfusion and/or glucose uptake. We will also determine whether there is an appreciable degree of improvement in myocardial-wall conditions subtended by affected and non-affected coronary vessels, and if this relates to changes in left ventricular function. METHODS: The DAPAHEART trial will be a phase III, single-center, randomized, two-arm, parallel-group, double-blind, placebo-controlled study. A cohort of 52 T2D patients with stable coronary artery disease (without any previous history of myocardial infarction, with or without previous percutaneous coronary intervention), with suboptimal glycemic control (glycated hemoglobin [HbA1c] 7-8.5%) on their current standard of care anti-hyperglycemic regimen, will be randomized in a 1:1 ratio to dapagliflozin or placebo. The primary outcome is to detect changes in myocardial glucose uptake from baseline to 4 weeks after treatment initiation. The main secondary outcome will be changes in myocardial blood flow, as measured by 13N-ammonia positron emission tomography/computed tomography (PET/CT). Other outcomes include cardiac function, glucose uptake in skeletal muscle, adipose tissue, liver, brain and kidney, as assessed by fluorodeoxyglucose (FDG) PET-CT imaging during hyperinsulinemic-euglycemic clamp; pericardial, subcutaneous and visceral fat, and browning as observed on CT images during FDG PET-CT studies; systemic insulin sensitivity, as assessed by hyperinsulinemic-euglycemic clamp, glycemic control, urinary glucose output; and microbiota modification. DISCUSSION: SGLT-2 inhibitors, in addition to their insulin-independent plasma glucose-lowering effect, are able to directly (substrate availability, fuel utilization, insulin sensitivity) as well as indirectly (cardiac after-load reduction, decreased risk factors for heart failure) affect myocardial functions. Our study will provide novel insights into how these drugs exert CV protection in a diabetic population. TRIAL REGISTRATION: EudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752.