[Gaps in evidence in recent cardiovascular guidelines: uncertainties in chronic coronary syndrome]. / "Gaps in evidence" nelle recenti linee guida cardiovascolari: incertezze nella sindrome coronarica cronica.

The clinical guidelines, while representing an objective reference to perform correct therapeutic choices, contain grey zones, where the recommendations are not supported by solid evidence. In the fifth National Congress Grey Zones held in Bergamo in June 2022, an attempt was made to highlight some of the main grey zones in Cardiology and, through a comparison between experts, to draw shared conclusions that can illuminate our clinical practice. This manuscript contains the statements of the symposium concerning the controversies regarding ischemic cardiomyopathy. The manuscript represents the organization of the meeting, with an initial review of the current guidelines on this topic, followed by an expert presentation of pros (White) and cons (Black) related to the identified "gaps of evidence". For every issue is then reported the "response" derived from the votes of the experts and the public, the discussion and, finally, the highlights, which are intended as practical take home messages to be used in the everyday clinical practice. The first gap in evidence discussed regards the validity of the indication to search for ischemia in light of the data from the ISCHEMIA trial. The second examines the possibility of modifying the algorithm proposed by the European guidelines on anti-ischemic therapy in chronic coronary syndromes. The last gap in evidence evaluates the comparability of long-term antithrombotic strategies in chronic coronary syndromes.

Association between heart and dementia keep an eye on the left atrium.

Atrial fibrillation is associated with an increased risk of cognitive impairment and dementia. The mechanisms are not well known, but they are probably multifactorial and involve atrial myopathy, cardio-embolism, cerebral hypoperfusion, and comorbidities (systemic vascular sclerosis, disease of the small cerebral vessels, inflammation, etc.). Atrial fibrillation therapy could have a protective effect on dementia through diversified actions: (i) prevention of left atrial remodelling; (ii) prevention of cardio-embolism and silent (and not) cerebral infarcts; (iii) improvement of cardiac output and cerebral perfusion. Randomized trials will be needed to clarify the links between left atrium and dementia and to identify the most appropriate therapeutic strategies.

Role of new drug therapies and innovative procedures in older patients with heart failure: from trials to clinical practice.

During earliest years, new drug-therapies and novel interventional therapies have been tested to modify the detrimental effect of secondary valve diseases, adverse ventricular remodelling and persistent fluid overload in HF patients. However, the increased prevalence of older or very old patients with HF has made their widespread implementation more problematic due to complex comorbidity, frailty, or overt disability. This growing older population, often excluded by randomized trials, but with elevated risk of hospitalization, required a different clinical and management approach that allows clinicians to take full advantage in reducing mortality and morbidity from these new pharmacological and instrumental therapies. In this perspective, the role of multidisciplinary Heart Team is mandatory for better define a correct decision-making process and tailoring the best pharmacological therapy in each patient and to program a continuum care in a post-acute phase of treatment. In addition, the possibility to plan multicentre registries of several complex cases evaluated by Heart Team could become a very important source of real world data to further refine indications and contraindications of different highly technological therapeutic approach, today based often on randomized clinical trials that do not represent faithfully the current clinical practice population.

The older patient with cardiovascular disease: background and clinical implications of the comprehensive geriatric assessment.

Principles and processes of comprehensive geriatric assessment (CGA) are increasingly being applied to subspecialties and subspecialty conditions, including cardiovascular patients (i.e., infective endocarditis; considerations of surgery or transcatheter aortic valve replacement, TAVR, for patients with aortic stenosis; vascular surgery) and postoperative mortality risk. In cardiovascular field CGA has mainly the aim to define ideal management according to the different typology of older adult patients (e.g., robust versus intermediate versus physical and cognitively disabled versus end-stage or dying), allowing physicians to select different therapeutic goals according to life expectancy; Aspect to be valued are by CGA are global health status and patient's decision-making capacity: CGA allows the individualized treatment definition and optimize the preprocedure condition.

Hypertension in the elderly: why one size does not fit all.

Over recent years, managing hypertension in older people has gained increasing attention, with reference to very old, frailer individuals. In these patients, hypertension treatment may be challenging due to a higher risk of hypotension-related adverse events which commonly overlaps with a higher cardiovascular risk. Additionally, frailer older adults rarely satisfy inclusion criteria of randomized clinical trials, which determines a substantial lack of scientific data. Although limited, available evidence suggests that the association between blood pressure and adverse outcomes significantly varies at advanced age according to frailty status. In particular, the negative prognostic impact of hypertension seems to attenuate or even revert in individuals with older biological age, e.g., patients with disability, cognitive impairment, and poor physical performance. Consequently, "one size does not fit all" and personalized treatment strategies are needed, customized to individuals' frailty and functional status. Similar to other cardiovascular diseases, hypertension management in older people should be characterized by a geriatric approach based on biological rather than chronological age and a geriatric comprehensive evaluation including frailty assessment is required to provide the most appropriate treatment, tailored to patients' prognosis and health care goals. The aim of this review was to illustrate the importance of a patient-centered geriatric approach to hypertension management in older people with the final purpose to promote a wider implementation of frailty assessment in routine practice.

Evidence and uncertainties in the management of atrial fibrillation in the elderly.

Atrial fibrillation (AF) is the most common cardiac sustained arrhythmia, whose incidence and prevalence increase with age, representing a significant burden for health services in western countries. Older people contribute to most patients affected from AF. Although oral anticoagulant therapy represents the cornerstone for the prevention of ischemic stroke and its disabling consequences, several other interventions - including left atrial appendage occlusion (LAAO), catheter ablation (CA) of AF, and rhythm control strategy (RCS) - have proved to be potentially effective in reducing the incidence of AF-associated clinical complications. Scientific literature focused on the three items will be discussed. Practical treatment of older AF patients is presented, including approach and management of patients with geriatric syndromes, selection of the most appropriate individualized drug treatment, clinical indications, and potential clinical benefit of LAAO and CA in selected older AF patients. Older people carry the greatest burden of AF in real world practice. Within a shared decision-making process, the patient centered approach needs to be put in the context of a comprehensive assessment, in order to gain maximal net clinical benefit and avoid futility or harm.

Severe aortic stenosis and transcatheter aortic valve replacement in elderly patients: utility vs. futility.

Recently, transcatheter aortic valve replacement (TAVR) has emerged as established standard treatment for symptomatic severe aortic stenosis, providing an effective, less-invasive alternative to open cardiac surgery for inoperable or high-risk older patients. In order to assess the anticipated benefit of aortic replacement, considerable interest now lies in better identifying factors likely to predict outcome. In the elderly population frailty and medical comorbidities have been shown to significantly predict mortality, functional recovery and quality of life after transcatheter aortic valve replacement. Scientific literature focused on the three items will be discussed. High likelihood of futility is described in patients with severe chronic lung, kidney, liver disease and/or frailty. The addition of frailty components to conventional risk prediction has been shown to result in improved discrimination for death and disability following the procedure and identifies those individuals least likely to derive benefit. Several dedicated risk score have been proposed to provide new insights into predicted "futile" outcome. However, assessment of frailty according to a limited number of variables is not sufficient, while a multi-dimensional geriatric assessment significantly improves risk prediction. A multidisciplinary heart team that includes geriatricians can allow the customization of therapeutic interventions in elderly patients to optimise care and avoid futility.

Relapse of chronic obstructive pulmonary disease and myocardial infarction: what is the connection?

Albeit largely underappreciated, chronic obstructive pulmonary disease (COPD) constitutes a major risk factor for cardiovascular diseases in general and for coronary disease in particular. The incidence of myocardial infarction, in fact increases rapidly, after relapse of COPD, with a peak event rate during the first week in the worst forms (those requiring hospitalization). Even though the precise mechanism is not completely defined, it is likely derived from two pathogenetic causes: (i) mismatch between myocardial demand and offer of O2 (not fully demonstrated and limited to few cases); (ii) acute coronary thrombosis, probably due to a systemic inflammatory reaction, brought upon by multiple interaction between the infective agent and the host immune system.

Pheochromocytoma presenting as an acute coronary syndrome complicated by acute heart failure: The challenge of a great mimic.

Pheochromocytoma is a rare neuroendocrine tumor with a highly variable clinical presentation. The serious and potentially lethal cardiovascular complications of these tumors are related to the effects of secreted catecholamines. We describe a case of a 50-year-old woman urgently admitted to our hospital because of symptoms and clinical and instrumental findings consistent with an acute coronary syndrome complicated by acute heart failure. Urgent coronary angiography showed normal coronary arteries. During her hospital stay, the recurrence of episodes characterized by a sudden increase in blood pressure, cold sweating, and nausea allowed us to hypothesize a pheochromocytoma. The diagnosis was confirmed by elevated levels of urinary catecholamines and by the finding of a left adrenal mass on magnetic resonance imaging. The patient underwent left adrenalectomy. Therefore, the initial diagnosis was critically reappraised and reviewed as a cardiac manifestation of a pheochromocytoma during catecholaminergic crisis.

Aspirin use for primary prevention in elderly patients.

The net clinical benefit of aspirin in primary prevention is uncertain as the reduction in occlusive events needs to be balanced against the increase in gastro-intestinal and cerebral bleedings. The meta-analysis of ATT (Anti Thrombotic Trialists) Collaboration in 2009 showed that aspirin therapy in primary prevention was associated with 12% reduction in cardio-vascular events, due mainly to a reduction in non-fatal myocardial infarction (0.18% vs 0.23% per year, p<0.0001). However, the benefit in term of coronary events was almost balanced by the increase in major bleedings. The balance between potential benefit and harm of aspirin differs in each person and appears to be favorable in subjects at higher cardio-vascular risk. Older people have increased risk of hemorrhage as well as increased risk of heart attack and stroke. As a consequence, it is important consider both likelihoods of benefits as well as harm within the lifespan and functioning of the person. The older people who most likely benefit from aspirin in primary prevention are those at higher cardio-vascular risk, with preserved functional abilities, low comorbidity, low risk of bleeding and a prolonged life expectancy.

Myocardial infarction and rupture after bronchial artery embolization.

Bronchial artery embolization is a well-known treatment for hemoptysis. Adverse events of this procedure include multiple systemic embolism and infarction. Myocardial infarction has been recently reported during bronchial artery embolization, owing to the presence of a coronary-to-bronchial artery fistula. We report the management of an ischemic left ventricular free wall rupture caused by bronchial artery embolization in a patient with massive hemoptysis, bronchiectasis, and undetected coronary-to-bronchial artery anomalous connection.

[The serotonin syndrome: why should cardiologists be aware and scared of it]. / Sindrome serotoninergica: perché anche il cardiologo la dovrebbe conoscere (e temere).

The serotonin syndrome (SS) represents a life-threatening adverse drug reaction, caused by serotonin overload in the central and peripheral nervous system, producing autonomic instability, neuromuscular and cardiovascular abnormalities, and cognitive alterations. The incidence of SS has been growing over the last few years, as a consequence of population aging and the steadily increasing use of pro-serotoninergic agents in clinical practice, in the presence of various comorbidities, mainly cardiovascular. Cardiologists often use combination therapies including serotoninergic agents, and should therefore consider the risk of serotoninergic adverse events caused by inappropriate drug interactions. SS is often difficult to diagnose and may be life-threatening if not adequately managed. Considering the several published case reports of overdose or not recommended associations, a greater awareness by clinicians about the potential risks associated with inappropriate use of these drugs is needed, as well as better information on the clinical features and therapeutic approaches to SS.

[Polytherapy and polypharmacy in elderly patients with chronic heart failure]. / Politerapia e polifarmacia nell'anziano con scompenso cardiaco cronico.

Population aging is associated with an increasing prevalence of chronic diseases (including chronic heart failure) and comorbidities (the presence of one or more diseases in addition to an index disease, potentially contributing to disability) which, in turn, expands the need for healthcare services. Therefore, the already elevated costs in the National Health Services are expected to rise further over the next decades, along with increasing aging of the population. This epidemiologic trend is responsible for the increasing occurrence of polytherapy (multiple medications prescribed to an individual patient) and polypharmacy (multiple medications not directly prescribed by a physician). Owing to often unpredictable interactions, polytherapy and polypharmacy are associated with higher risk of adverse drug reactions with increased mortality and hospitalizations that contribute to increase direct and indirect National Health Services costs. Physicians, patients and caregivers should be instructed in strategies aimed at reducing adverse drug reactions while maintaining optimal management of conditions that, such as chronic heart failure, are at high risk of death, functional impairment and deteriorated quality of life. Strategies consist of a variety of interventions, such as reducing inappropriate medication prescriptions and number of medications and doses taken, avoiding drugs with greater potential of interactions, and increasing patient adherence.

[Statins and the "Cabala": the new Note 13]. / Statine e Cabala: la nuova Nota 13.

The new Note 13 introduces significant changes in the regulation of statin reimbursement. Although cardiovascular risk assessment still plays a key role, cardiovascular risk estimation has shifted from the "risk charts" to the more simple "sum of risk factors". In addition, the new Note 13 expands drug reimbursement to subjects at intermediate risk, who represent the main source of cardiovascular events because of the size of the population. As a consequence, the general trend of the new Note 13 is to simplify the rules that govern statin reimbursement and to guarantee treatment for all subjects at increased risk of cardiac and vascular events.

Simultaneous analysis of kynurenine and tryptophan in human plasma by capillary electrophoresis with UV detection.

Plasma kynurenine (Kyn)/tryptophan ratio has been proposed as a useful marker for the monitoring activation of the cellular immune system. Here, we describe an easy capillary electrophoresis method with UV detection for the separation and detection of Kyn and tryptophan in human plasma using methltryptophan as internal standard. The plasma samples were simply treated with acentonitrile for the elimination of proteins, the supernatant was evaporated, and the dried sample was resuspended with water and directly injected on the capillary without sample derivatization procedures. The use of a run buffer composed by 100 mmol/L Bis-Tris propane at pH 2.15 allowed to baseline resolve the analytes within 9 min. Precision tests indicated a good repeatability of our method both for times (CV< 0.53%) and areas (CV< 2.8%). Moreover, a good reproducibility of intra-assay and interassay tests was obtained (CV < 3.9% and CV < 7.6%, respectively). The obtained limit of detections for Kyn and tryptophane, evaluated at 226 nm, were 0.15 and 0.40 µmol/L, respectively. The method suitability was tested by measuring analyte levels both in healthy volunteers, acute myocardial infarction and chronic kidney disease patients.