Remote monitoring of severe heart failure.

Patients with advanced heart failure, due to the instability of their clinical conditions, need close surveillance to avoid dangerous exacerbations or sudden events. Digital technology can be of great help in this contest, thanks to remote monitoring, made possible with the use of wearable or implantable instruments. The latter are currently generally inserted inside defibrillators or resynchronization systems, or inserted inside the pulmonary circulation for monitoring pulmonary pressure. Parameters such as thoracic impedance, physical activity, heart rate variability, atrial and ventricular arrhythmias, blood pressure, and O2 saturation can be controlled remotely. The data relating to the actual benefit in terms of avoidable events (death and hospitalizations) are not definitive, but certainly from an organizational point of view, the benefit is evident, both on the part of the patient and of the organization of care. The latter, provided in the form of televisits, requires a re-modulation of the system, making use of trained personnel, a well-structured network, and digital technologies (platforms, electronic health records) that are not yet perfectly developed. The evolution of the solutions offered by artificial intelligence guarantees a rapid and progressive refinement of telemedicine in this sector.

Sudden death in ischemic heart disease: looking for new predictors: polygenic risk.

The phenomenon of sudden death (SD) occurs, in 70% of cases, in people who do not fall within the indications of the guidelines relating to the implantation of the defibrillator. There is a way of inheriting the risk condition by genetic means, the polygenic one, in which mutations are not found, but an increase in alleles of common variations called polymorphisms. The PRE-DETERMINE cohort study has the primary objective of determining whether biological markers, and electrocardiogram can be used to identify individuals more likely to experience SD. Within the study, we investigated the utility of the genome-wide polygenic score for coronary artery disease (GPSCAD) for SD risk stratification in an intermediate-risk population with stable coronary artery disease without severe systolic dysfunction and/or indication for an implantable cardioverter defibrillator in primary prevention. Over a mean follow-up period of 8.0 years, patients in the top decile of GPSCAD were at higher absolute (8.0% vs. 4.8%; P < 0.005) and relative (29% vs. 16%; P < 0.0003) risk of SD compared to the rest of the cohort. No association was found between the highest decile of GPSCAD and other forms of death, cardiac, and non-cardiac. The data on the increase in absolute and relative terms of SD can be used, at this stage, only for a theoretical estimate on the possible efficacy of the defibrillator in the population with chronic coronary artery disease and moderately depressed left ventricular function as number needed to treat and possible reduction of mortality in high-risk patients (those included in the top decile of GPSCAD).

IGFBP7 and GDF-15, but not P1NP, are associated with cardiac alterations and 10-year outcome in an elderly community-based study.

BACKGROUND: Little is known about the clinical value of Insulin-like growth factor-binding protein-7 (IGFBP7), a cellular senescence marker, in an elderly general population with multiple co-morbidities and high prevalence of asymptomatic cardiovascular ventricular dysfunction. Inflammation and fibrosis are hallmarks of cardiac aging and remodelling. Therefore, we assessed the clinical performance of IGFBP7 and two other biomarkers reflecting these pathogenic pathways, the growth differentiation factor-15 (GFD-15) and amino-terminal propeptide of type I procollagen (P1NP), for their association with cardiac phenotypes and outcomes in the PREDICTOR study. METHODS: 2001 community-dwelling subjects aged 65-84 years who had undergone centrally-read echocardiography, were selected through administrative registries. Atrial fibrillation (AF) and 4 echocardiographic patterns were assessed: E/e' (> 8), enlarged left atrial area, left ventricular hypertrophy (LVH) and reduced midwall circumference shortening (MFS). All-cause and cardiovascular mortality and hospitalization were recorded over a median follow-up of 10.6 years. RESULTS: IGFBP7 and GDF-15, but not P1NP, were independently associated with prevalent AF and echocardiographic variables after adjusting for age and sex. After adjustment for clinical risk factors and cardiac patterns or NT-proBNP and hsTnT, both IGFBP7 and GDF-15 independently predicted all-cause mortality, hazard ratios 2.13[1.08-4.22] and 2.03[1.62-2.56] per unit increase of Ln-transformed markers, respectively. CONCLUSIONS: In a community-based elderly cohort, IGFBP7 and GDF-15 appear associated to cardiac alterations as well as to 10-year risk of all-cause mortality.

Sex differences in factors associated with heart failure and diastolic left ventricular dysfunction: a cross-sectional population-based study.

BACKGROUND: Although sex differences in cardiovascular diseases are recognised, including differences in incidence, clinical presentation, response to treatments, and outcomes, most of the practice guidelines are not sex-specific. Heart failure (HF) is a major public health challenge, with high health care expenditures, high prevalence, and poor clinical outcomes. The objective was to analyse the sex-specific association of socio-demographics, life-style factors and health characteristics with the prevalence of HF and diastolic left ventricular dysfunction (DLVD) in a cross-sectional population-based study. METHODS: A random sample of 2001 65-84 year-olds underwent physical examination, laboratory measurements, including N-terminal pro-B-type natriuretic peptide (NT-proBNP), electrocardiography, and echocardiography. We selected the subjects with no missing values in covariates and echocardiographic parameters and performed a complete case analysis. Sex-specific multivariable logistic regression models were used to identify the factors associated with the prevalence of the diseases, multinomial logistic regression was used to investigate the factors associated to asymptomatic and symptomatic LVD, and spline curves to display the relationship between the conditions and both age and NT-proBNP. RESULTS: In 857 men included, there were 66 cases of HF and 408 cases of DLVD (77% not reporting symptoms). In 819 women, there were 51 cases of HF and 382 of DLVD (79% not reporting symptoms). In men, the factors associated with prevalence of HF were age, ischemic heart disease (IHD), and suffering from three or more comorbid conditions. In women, the factors associated with HF were age, lifestyles (smoking and alcohol), BMI, hypertension, and atrial fibrillation. Age and diabetes were associated to asymptomatic DLVD in both genders. NT-proBNP levels were more strongly associated with HF in men than in women. CONCLUSIONS: There were sex differences in the factors associated with HF. The results suggest that prevention policies should consider the sex-specific impact on cardiac function of modifiable cardiovascular risk factors.

New prevention scenarios: polygenic risk.

Although coronary heart disease is a highly preventable disease, it is still the leading cause of morbidity and mortality in developed countries. This is also due to the fact that the risk models used in clinical practice have proved ineffective in identifying people at risk: up to 30% of cases of myocardial infarction do not have traditional risk factors used in risk estimation models. Although the genetic component of myocardial infarction has been known for many years, with an inheritance rate of between 40% and 60%, it is not yet used as a risk factor in primary prevention models such as the Heart Card or the European SCORE. Recent advances in genomics and the use of clinical big data have allowed the development of genetic risk scores called Polygenic Risk Score (PRS), capable of identifying populations with average LDL-C levels, but with the same risk of heart attack of carriers of hypercholesterolaemia. The clinical usefulness of the PRS lies precisely in identifying high-risk individuals who are invisible to traditional models. The clinical applications of PRS for coronary artery disease are discussed in this report.

Beyond CHA2DS2-VASc in atrial fibrillation: the atrium and the risk of stroke.

Pathology affecting the atria have a significant impact on the occurrence of arrhythmias and the risk of stroke. The causal relationship between atrial fibrillation (AF) and ischaemic stroke has been challenged by the recent uncovering of the lack of temporal association between thrombo-embolic cerebral events and paroxysmal AF or tachycardia. General conditions, such as the one considered in the definition of the CHA2DS2-VASc score, or specific atrial pathology (also independently occurring), could predispose to cerebral embolism.

Predictive value of interatrial block for atrial fibrillation in elderly subjects enrolled in the PREDICTOR study.

AIMS: The principal aims of this prospective multicentre study were to relate the presence of interatrial block (IAB) with a late occurrence of atrial fibrillation (AF) and to demonstrate the independence of the IAB effect on risk of AF from structural cardiac alterations. METHODS: This prospective study was the follow-up of subjects included in the PREDICTOR cross-sectional population-based study. Subjects were divided into groups according to IAB status. Socio-demographic and health characteristic were collected during enrolment in the PREDICTOR along with ECGs, echocardiograms and NT-proBNP dosages. Follow up was performed on administrative data. The mean time of follow up was 6.6 years. RESULTS: 1626 subjects were included in the analysis. Four hundred-fifteen subjects out of 1626 (25.5%) had IAB. The survival analysis suggests an association between IAB alone and AF (HR = 1.50, p = 0.058) and, in normal-weight subjects, IAB strongly predicted AF indicating more than triple the risk (HR = 3.05; p = 0.002 95% CI: 1.51-6.18). The association seems to be independent of possible confounders such as history of IHD, left ventricular hypertrophy, CHA2DS2-VASc, left atrial dimension, or NT-proBNP dosage. CONCLUSION: Our analysis suggests that IAB is an electric condition that can increase the risk of AF independently of any structural cardiac alterations, at least in normal-weight subjects.

Heart failure in the elderly: A geriatric syndrome. Picture of the modern situation.

Among the older patients' cohort, the aetiology of heart failure is peculiar and differs in many ways from the younger one, both in its epidemiology, diagnostic work-up and clinical presentation. Focusing on this population, we could assume that heart failure is a real geriatric syndrome, characterized by several features, which coexist with other comorbidities and require specific and targeted cares. It is therefore necessary to examine the global burden of heart failure and the patient's history rather than the causal cardiomyopathy - frequently more than one in the elderly - facing with the condition, bearing in mind the quality of life even before its duration.

Galectin-3 and the Mineralocorticoid Receptor Antagonist Canrenone in Mild Heart Failure.

BACKGROUND: Galectin-3 (Gal-3) is involved in collagen deposition and inflammation and is a prognostic biomarker in heart failure (HF).Methods and Results:Gal-3 and other markers of fibrosis or cardiac stress were measured serially in 413 patients with mild HF randomized to the mineralocorticoid receptor antagonist canrenone or placebo to evaluate treatment effect and association with clinical outcome. Gal-3 increased slightly over 6 months in both arms of the study and was associated with clinical endpoints. CONCLUSIONS: Although Gal-3 showed prognostic value, the effect of canrenone on clinical outcomes was unaffected by baseline concentrations of biomarkers of fibrosis or cardiac stress.

Preoperative risk evaluation in patients over 75 years candidates to non-cardiac and cardiac surgery.

In the 24th and 25thof June 2016, 80 national experts were invited to Rome from The Italian Society of Geriatric Cardiology and the Italian Association of Cardiovascular Prevention and Rehabilitation to revise the current knowledge on the perioperative risk in the elderly. Cardiologists, geriatricians, heart and general surgeons and anesthesiologists discussed the topic with the objective of reaching a consensus and to launch observational research and registries in the field of perioperative risk evaluation in the elderly. The introduction of objective measures of frailty on top of traditional cardiac evaluation in the different surgical contexts could allow for a more precise definition of "surgical risk", appropriate perioperative management and postoperative outcome.

Anticoagulation in atrial fibrillation. A large real-world update.

INTRODUCTION: In a large nationwide administrative database including ∼35 % of Italian population, we analyzed the impact of oral anticoagulant treatment (OAT) in patients with a hospital diagnosis of non-valvular atrial fibrillation (NVAF). METHODS AND RESULTS: Of 170404 OAT-naïve patients (mean age 78.7 years; 49.4 % women), only 61.1 % were prescribed direct oral anticoagulants, DOACs, or vitamin-K antagonists, VKAs; 14.2 % were given aspirin (ASA), and 24.8 % no anti-thrombotic drugs (No Tx). We compared ischemic stroke (IS), IS and systemic embolism (IS/SE), intracranial hemorrhage (ICH), major bleeding (MB), major gastro-intestinal bleeding, all-cause deaths and the composite outcome, across four propensity-score matched treatment cohorts with >15400 patients each. Over 2.9±1.5 years, the incidence of IS and IS/SE was slightly less with VKAs than with DOACs (1.62 and 1.84 vs 1.81 and 1.99 events.100 person-years; HR=0.85, 95%CI=0.76-0.95 and HR=0.87, 95%CI=0.78-0.97). This difference disappeared in a sensitivity analysis which excluded those patients treated with low-dose of apixaban, edoxaban, or rivaroxaban (41.7% of DOACs cohort). Compared with DOACs, VKAs were associated with greater incidence of ICH (1.09 vs 0.81; HR=1.38, 95%CI=1.17-1.62), MB (3.78 vs 3.31; HR=1.14, 95%CI=1.02-1.28), all-cause mortality (9.66 vs 10.10; HR=1.07, 95%CI=1.02-1.11), and composite outcome (13.72 vs 13.32; HR=1.04, 95%CI=1.01-1.08). IS, IS/SE, and mortality were more frequent with ASA or No Tx than with VKAs or DOACs (p<0.001 for all comparisons). CONCLUSIONS: Beyond confirming the association with a better net clinical benefit of DOACs over VKAs, our findings substantiate the large proportion of NVAF patients still inappropriately anticoagulated, thereby reinforcing the need for educational programs.

[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.

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.

[Progress in cardiovascular prevention: from risk charts to polygenic risk score and precision prevention]. / Progressi in prevenzione cardiovascolare: dalle carte del rischio allo score poligenico e alla prevenzione di precisione.

In the last few decades, great epidemiological studies identified the main risk factors and their causative role in cardiovascular diseases (CVD). In this field, the pivotal study was the Framingham Heart Study for the evaluation of classical risk factors and for the production of initial instruments of risk calculation. The Seven Countries Study of Cardiovascular Diseases was the first to compare the influence of different cultural environments on the risks of developing atherosclerosis. In 1980, the Italian Journal of Cardiology published an extensive evaluation of risk factors in nine Italian communities. Since the early '90s, the first risk charts for global and individual risk evaluation were available (Framingham, SCORE, PROCAM, CUORE). Mortality reduction in the period of 1980-2000 can be attributed to risk factor reduction in primary prevention (55%) and to pharmacological treatment in the acute phase of the disease or in secondary prevention (40%). Two important longitudinal studies have been conducted in Italy in the periods of 1998-2002 and 2008-2012 thanks to the cooperation of the National Association of Hospital Cardiologists (ANMCO) and the National Health Institute (ISS), which became the reference point for the influence of lifestyle and risk factors on CVD. During the last 15 years, genetic studies allowed the construction of polygenic risk scores (PRS), that are strongly predictive of developing CVD in the future, thanks to big genomic datasets of individuals followed for more than 10 years (e.g. UK Biobank). PRS can be used as an adjunctive tool to the common risk charts for a better classification of individual risk profile. In addition to PRS, inflammation biomarkers and imaging tools like ultrasound and coronary calcium score and their integration with machine learning can help in the best definition of cardiovascular risk. Precision prevention by the study of "metabotypes" and community prevention provide possible future development of cardiovascular prevention.