Myocardial perfusion imaging in very elderly patients with suspected coronary artery disease: Never too late!

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β-adrenergic receptors and G protein-coupled receptor kinase-2 in Alzheimer's disease: a new paradigm for prognosis and therapy?

Alzheimer's disease (AD) is a devastating form of dementia that imposes a severe burden on health systems and society. Although several aspects of AD pathogenesis have been elucidated over the last few decades, many questions still need to be addressed. In fact, currently available medications only provide symptomatic improvement in patients with AD without affecting disease progression. The β-adrenergic receptor (β-AR) system can be considered a possible target that deserves further exploration in AD. The central noradrenergic system undergoes substantial changes in the course of AD and β-ARs have been implicated not only in amyloid formation in AD brain but also in amyloid-induced neurotoxicity. Moreover, clinical evidence suggests a protective role of β-AR blockers on AD onset. In addition to that, post-receptor components of β-AR signaling seem to have a role in AD pathogenesis. In particular, the G protein coupled receptor kinase 2, responsible for β-AR desensitization and downregulation, mediates amyloid-induced β-AR dysfunction in neurons, and its levels in circulating lymphocytes of AD patients are increased and inversely correlated with patient's cognitive status. Therefore, there is an urgent need to gain further insight on the role of the adrenergic system components in AD pathogenesis in order to translate preclinical and clinical knowledge to more efficacious prognostic and therapeutic strategies

Cardiac computed tomography and myocardial perfusion scintigraphy for risk stratification in asymptomatic individuals without known cardiovascular disease: a position statement of the Working Group on Nuclear Cardiology and Cardiac CT of the European Society of Cardiology

Cardiovascular events remain one of the most frequent causes of mortality and morbidity worldwide. The majority of cardiac events occur in individuals without known coronary artery disease (CAD) and in low- to intermediate-risk subjects. Thus, the development of improved preventive strategies may substantially benefit from the identification, among apparently intermediate-risk subjects, of those who have a high probability for developing future cardiac events. Cardiac computed tomography and myocardial perfusion scintigraphy (MPS) by single photon emission computed tomography may play a role in this setting. In fact, absence of coronary calcium in cardiac computed tomography and inducible ischaemia in MPS are associated with a very low rate of major cardiac events in the next 3-5 years. Based on current evidence, the evaluation of coronary calcium in primary prevention subjects should be considered in patients classified as intermediate-risk based on traditional risk factors, since high calcium scores identify subjects at high-risk who may benefit from aggressive secondary prevention strategies. In addition, calcium scoring should be considered for asymptomatic type 2 diabetic patients without known CAD to select those in whom further functional testing by MPS or other stress imaging techniques may be considered to identify patients with significant inducible ischaemia. From available data, the use of MPS as first line testing modality for risk stratification is not recommended in any category of primary prevention subjects with the possible exception of first-degree relatives of patients with premature CAD in whom MPS may be considered. However, the Working Group recognizes that neither the use of computed tomography for calcium imaging nor of MPS have been proven to significantly improve clinical outcomes of primary prevention subjects in prospective controlled studies. This information would be crucial to adequately define the role of imaging approaches in cardiovascular preventive strategie

Waist-to-hip ratio and mortality in heart failure

Aims: A higher body mass index (BMI) is associated with better survival in heart failure (HF) patients, also known as the obesity paradox. However, BMI does not account for body composition. We therefore analysed the association between abdominal fat, measured via waist‐to‐hip ratio (WHR), BMI and all‐cause mortality in patients with HF. Methods and results: For this analysis, 1738 patients from the Scottish BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT‐CHF) validation study were included. Patients without waist and hip measurements were excluded. WHR was defined as waist circumference/hip circumference, divided into tertiles and split for sex. A linear regression of principal components from an extensive panel of biomarkers was performed to provide insight in the pathophysiology behind a higher WHR. In total, 1479 patients were included, of which 33% were female and mean age was 75 ±11 years. A higher WHR was independently associated with a higher BMI, a higher prevalence of diabetes and higher New York Heart Association functional class. There was a significant interaction between sex and WHR on its association with mortality (P <0.001). In women, a higher WHR was associated with a higher mortality risk [hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.37–3.63; P =0.001], whereas no significant association was found in men (HR 0.87, 95% CI 0.63–1.20; P = 0.409). We found a strong association between a higher WHR and elevated markers of inflammation and MAPK cascade in women, while these associations were less profound in men. Conclusions: A higher WHR was associated with a higher risk of death in female but not in male HF patients. These findings challenge the obesity paradox, and suggest that fat deposition is pathophysiologically harmful and may be a target for therapy in female patients with HF

Heart failure outpatient clinics resources in Italy: a viewpoint of Italian Society of Cardiology organization

The current paper reports the model organization, level of health care, and type of medical and research activities related to the existing heart failure centers of the Italian Society of Cardiology. Of note, we conduced an internal survey among the members of heart failure working group and related hospital and territorial sites about the quality of care and assistance levels according to the local hospital resources and type of diagnostic therapeutic and management resources. Thirty-two hospital ambulatorial structures have been identified, the centers were equally distributed within the national ground, with similar concentration between north and south regions of the Italian country. We distinguished three different levels of organization: (1) basal territorial clinics in which patients with suspected or already diagnosed heart failure (HF) are initially identified and screened; (2) intermediate clinics in which HF patients can be routinary followed by HF specialists supported by a dedicated staff including imaging and arrythmologist experts, and interventional cardiologist; (3) advanced clinics composed by all the technical and staff resources capable of guarantying repetitive invasive assessment, continuous invasive monitoring, dedicated telemedicine structures focused on more advanced HF management integrated by heart transplantation or mechanical assistance programs. Different type of assistance is supported by a relevant number of research activity primarily conducted by the Italian Society of Cardiology or spontaneous studies arranged by HF specialist members. The number of HF centers has increased over the past few decades in proportion to the progressive rise in HF diagnoses and associated hospitalization. The expansion of ambulatory structures has been facilitated by an increasing socioeconomic and research influence. The quality of HF services in Italy could be raised by improving the network and connections between HF specialists, general practitioners (GPs), caregivers, and other specialists frequently working in this field

Sharing the multidisciplinary clinical approach to peri- and postmenopausal women. A Delphi consensus among Italian gynecologists, endocrinologists, and cardiologists for an integrated and optimal approach to clinical practice

Objective: The critical phase of perimenopausal period is marked by a reduction in estrogen levels, leading to various clinical issues (vasomotor and neurodegenerative symptoms, increased osteoporosis risk and cardiovascular risk). These complex clinical scenarios pose challenges to clinicians in providing the right support for diagnosis and treatment. A group of Italian cardiologists, endocrinologists, and gynecologists conducted a survey among expert colleagues to assess consensus on controversial issues and best practices for screening and treating peri- and postmenopausal women. Methods: The Delphi methodology was used to analyze responses from a qualitative expert panel comprising 25 cardiologists, 25 endocrinologists, and 25 gynecologists, selected nationwide. Two consecutive questionnaires were proposed between February and May 2023. Agreement among experts was assessed following the Delphi method as developed by the RAND Corporation. Results: The results of this Delphi Consensus have been shared by the leading scientific societies: Italian Society of Cardiology, Italian Society of Endocrinology, Italian Society of Gynecology and Obstetrics, and Italian Hospital Obstetricians Gynecologists Association. Conclusions: The experts highlighted comorbidities and hormone deprivation as crucial clinical problems to be evaluated in perimenopausal women, requiring investigation from cardiovascular and endocrinologic perspectives to assess cardiovascular risk, involving the use of BMI, standard blood samples, endocrine-metabolic tests, and lifestyle assessment, particularly in women with higher cardiovascular and metabolic risks candidates for hormone replacement therapy (HRT). The experts also agreed on the benefits of HRT in improving lipid metabolism and reducing insulin resistance, thereby mitigating the metabolic risks associated with menopause. However, this therapy should be tailored considering individual women's comorbidities and thrombotic risk

Evaluation of Drug Interactions in Patients Treated with DAAs for Hepatitis C Therapy with Comorbidities and Cardiovascular Issues—A Delphi Consensus Project

Orally administered direct-acting antivirals (DAAs) have dramatically changed the possibility of curing HCV (hepatitis C virus) infection, with the two principal HCV regimens based on the combination of glecaprevir + pibrentasvir (GLE-PIB) and sofosbuvir + velpatasvir (SOF-VEL). A combination of drugs containing NS3/4A protease inhibitors, as well as the fact that almost all HCV patients can be treated at present, may expose patients to a higher rate of drug–drug interactions (DDIs). The hepatitis C treatment recommendations from the EASL (European Association for the Study of the Liver) state that, prior to starting treatment with a DAA, a detailed drug history should be taken; yet, the decision on managing the potential DDIs is not always clear. For this reason, a group of Italian cardiologists and hepatologists promoted a survey among colleagues to assess the controversial issues when treating patients with chronic hepatitis C taking concomitant cardiovascular drugs, aiming to reach a consensus on the best practice to apply when treating a patient with chronic hepatitis C who is taking concomitant drugs for cardiovascular diseases. Two consecutive questionnaires were proposed between June and July 2022 to a qualitative Expert Panel (EP) of 14 gastroenterologists, infectologists, hepatologists, and internists, with statistical analyses performed on 100% of the responses for both questionnaires. Agreement among experts was assessed following the Delphi method as developed by the RAND Corporation. The interviewed experts consider DDIs a critical clinical problem to be evaluated in HCV patients. Therefore, dose changes, drug substitution, and discontinuation of concomitant cardiovascular drugs should be discouraged, even if planned for a relatively short period. Since oral DAAs have different DDIs profiles, hepatologists should prefer the antiviral DAA combination presenting the lowest instance of potential interactions