Standardised Exercise Prescription for Patients with Chronic Coronary Syndrome and/or Heart Failure: A Consensus Statement from the EXPERT Working Group.

Whereas exercise training, as part of multidisciplinary rehabilitation, is a key component in the management of patients with chronic coronary syndrome (CCS) and/or congestive heart failure (CHF), physicians and exercise professionals disagree among themselves on the type and characteristics of the exercise to be prescribed to these patients, and the exercise prescriptions are not consistent with the international guidelines. This impacts the efficacy and quality of the intervention of rehabilitation. To overcome these barriers, a digital training and decision support system [i.e. EXercise Prescription in Everyday practice & Rehabilitative Training (EXPERT) tool], i.e. a stepwise aid to exercise prescription in patients with CCS and/or CHF, affected by concomitant risk factors and comorbidities, in the setting of multidisciplinary rehabilitation, was developed. The EXPERT working group members reviewed the literature and formulated exercise recommendations (exercise training intensity, frequency, volume, type, session and programme duration) and safety precautions for CCS and/or CHF (including heart transplantation). Also, highly prevalent comorbidities (e.g. peripheral arterial disease) or cardiac devices (e.g. pacemaker, implanted cardioverter defibrillator, left-ventricular assist device) were considered, as well as indications for the in-hospital phase (e.g. after coronary revascularisation or hospitalisation for CHF). The contributions of physical fitness, medications and adverse events during exercise testing were also considered. The EXPERT tool was developed on the basis of this evidence. In this paper, the exercise prescriptions for patients with CCS and/or CHF formulated for the EXPERT tool are presented. Finally, to demonstrate how the EXPERT tool proposes exercise prescriptions in patients with CCS and/or CHF with different combinations of CVD risk factors, three patient cases with solutions are presented.

Artificial intelligence in cardiovascular prevention: new ways will open new doors.

Prevention and effective treatment of cardiovascular disease are progressive issues that grow in tandem with the average age of the world population. Over recent decades, the potential role of artificial intelligence in cardiovascular medicine has been increasingly recognized because of the incredible amount of real-world data (RWD) regarding patient health status and healthcare delivery that can be collated from a variety of sources wherein patient information is routinely collected, including patient registries, clinical case reports, reimbursement claims and billing reports, medical devices, and electronic health records. Like any other (health) data, RWD can be analysed in accordance with high-quality research methods, and its analysis can deliver valuable patient-centric insights complementing the information obtained from conventional clinical trials. Artificial intelligence application on RWD has the potential to detect a patient's health trajectory leading to personalized medicine and tailored treatment. This article reviews the benefits of artificial intelligence in cardiovascular prevention and management, focusing on diagnostic and therapeutic improvements without neglecting the limitations of this new scientific approach.

Exercise Training in Elderly Cancer Patients: A Systematic Review.

Due to the aging of the population, in 70% of cases, a new cancer diagnosis equals a cancer diagnosis in a geriatric patient. In this population, beyond the concept of mortality and morbidity, functional capacity, disability, and quality of life remain crucial. In fact, when the functional status is preserved, the pathogenetic curve towards disability will stop or even regress. The present systematic review investigated the effectiveness of physical exercise, as part of a holistic assessment of the patient, for preventing disability and improving the patient's quality of life, and partially reducing all-cause mortality. This evidence must point towards decentralization of care by implementing the development of rehabilitation programs for elderly cancer patients either before or after anti-cancer therapy.

Potential Role of Global Longitudinal Strain in Cardiac and Oncological Patients Undergoing Cardio-Oncology Rehabilitation (CORE).

Although shown to be effective in improving survival and quality of life in patients with cancer, some treatments are well-known causes of cardiotoxicity, such as anthracyclines, monoclonal antibodies against human epidermal growth factor receptor 2 (HER2) and radiotherapy. To prevent cardiovascular disease (CVD) in patients living with cancer, cardiologists and oncologists promoted the development of cardio-oncology, an interdisciplinary field which aims to further improving life expectancy in these patients. Cardio-oncology rehabilitation (CORE), through correction of risk factors, prescription of drug therapies and structured exercise programs, tries to improve symptoms, quality of life, cardiorespiratory fitness (CRF) and survival in patients with cancer. Different imaging modalities can be used to evaluate the real effectiveness of exercise training on cardiac function. Among these, the global longitudinal strain (GLS) has recently aroused interest, thanks to its high sensitivity and specificity for cardiac dysfunction detection due to advanced ultrasound programs. This review summarizes the evidence on the usefulness of GLS in patients with cancer undergoing cardiac rehabilitation programs.

The need for long-term personalized management of frail CVD patients by rehabilitation and telemonitoring: A framework.

Due to advances in cardiovascular medicine and preventive cardiology, patients benefit from a better prognosis, even in case of significant disease burden such as acute and chronic coronary syndromes, advanced valvular heart disease and chronic heart failure. These advances have allowed CVD patients to increase their life expectancy, but on the other hand also experience aging-related syndromes such as frailty. Despite being underrecognized, frailty is a critical, common, and co-existent condition among older CVD patients, leading to exercise intolerance and compromised adherence to cardiovascular rehabilitation (CR). Moreover, frail patients need a different approach for CR and are at very high risk for adverse events, but yet are underrepresented in conventional CR. Fortunately, recent advances have been made in technology, allowing remote monitoring, coaching and supervision of CVD patients in secondary prevention programs with promising benefits. Similarly, we hypothesized that such programs should also be implemented to treat frailty in CVD patients. However, considering frail patients' particular needs and challenges, telerehabilitation interventions should thus be appropriately adapted. Our purpose is to provide, for the first time and based on expert opinions, a framework of how such a cardiac telerehabilitation program could be developed and implemented to manage a prevention and rehabilitation program for CVD patients with frailty.

Characterization of Thermoluminescent Dosimeters for Neutron Dosimetry at High Altitudes.

Neutrons constitute a significant component of the secondary cosmic rays and are one of the most important contributors to natural cosmic ray radiation background dose. The study of the cosmic ray neutrons' contribution to the dose equivalent received by humans is an interesting and challenging task for the scientific community. In addition, international regulations demand assessing the biological risk due to radiation exposure for both workers and the general population. Because the dose rate due to cosmic radiation increases significantly with altitude, the objective of this work was to characterize the thermoluminescent dosimeter (TLDs) from the perspective of exposing them at high altitudes for longtime neutron dose monitoring. The pair of TLD-700 and TLD-600 is amply used to obtain the information on gamma and neutron dose in mixed neutron-gamma fields due to the present difference in 6Li isotope concentration. A thermoluminescence dosimeter system based on pair of TLD-600/700 was characterized to enable it for neutron dosimetry in the thermal energy range. The system was calibrated in terms of neutron ambient dose equivalent in an experimental setup using a 241Am-B radionuclide neutron source coated by a moderator material, polyethylene, creating a thermalized neutron field. Afterward, the pair of TLD-600/700 was exposed at the CERN-EU High-Energy Reference Field (CERF) facility in Geneva, which delivers a neutron field with a spectrum similar to that of secondary cosmic rays. The dosimetric system provided a dose value comparable with the calculated one demonstrating a good performance for neutron dosimetry.

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Use for Atherogenic Dyslipidemia in Solid Organ Transplant Patients.

Dyslipidemia is a widespread risk factor in solid organ transplant patients, due to many reasons, such as the use of immunosuppressive drugs, with a consequent increase in cardiovascular diseases in this population. PCSK9 is an enzyme mainly known for its role in altering LDL levels, consequently increasing cardiovascular risk. Monoclonal antibody PCSK9 inhibitors demonstrated remarkable efficacy in the general population in reducing LDL cholesterol levels and preventing cardiovascular disease. In transplant patients, these drugs are still poorly used, despite having comparable efficacy to the general population and giving fewer drug interactions with immunosuppressants. Furthermore, there is enough evidence that PCSK9 also plays a role in other pathways, such as inflammation, which is particularly dangerous for graft survival. In this review, the current evidence on the function of PCSK9 and the use of its inhibitors will be discussed, particularly in transplant patients, in which they may provide additional benefits.

Short-term treatment of iron deficiency anemia after cardiac surgery.

Iron deficiency anemia (IDA) is frequent after cardiac surgery and is associated with increased morbidity and mortality. In a retrospective study, we analyzed 106 patients with IDA (hemoglobin [Hb] ≤ 12 g/dl in women and ≤ 13 g/dl in men, transferrin saturation [TSAT] ≤ 20%) on admission to a Cardiac Rehabilitation Unit after cardiac surgery. The patients were divided into two groups, one was treated with oral sucrosomial iron (SI) and the other with intravenous ferric carboxymaltose (FCM). Patients received a single 1000 mg dose of FCM from the day after admission to rehabilitation (T1), or a 120 mg/day dose of SI from T1 until discharge (T2); after discharge, SI was reduced to 30 mg/day until the end of follow-up (T3). Hb was evaluated at T1, T2 and T3; the other hematological parameters at T1 and T3; natriuretic peptides at T1, T2 and T3; 6-minute walk test (6MWT) at T1 and T2. Folate, vitamin B12 and reticulocytes were sampled on admission. Folate deficiency was documented in 60.4% of patients. Hb increased in both groups with no significant differences between the two treatments (p = 0.397). The other iron metabolism parameters (sideremia, transferrin, TSAT) displayed similar behavior, showing a significant increase at T3 (p < 0.001) with both therapies, although the increase was faster with FCM. Ferritin - high on admission - decreased at T3 in the SI group and rose significantly in the FCM group (SI 219.5 vs. FCM 689 ng/ml p < 0.0001). The 6MWT increased significantly at T2, with an overlap between SI and FCM. In conclusion, the results of this study show that SI and FCM exhibit the same effectiveness on IDA; the response time to therapy of both treatments is also equally fast. SI and FCM induce a similar increase in functional capacity. The study shows that SI can be a viable alternative to FCM after cardiac surgery in terms of effectiveness and tolerability.

Frailty Test Battery Development including Physical, Socio-Psychological and Cognitive Domains for Cardiovascular Disease Patients: A Preliminary Study.

Frailty is an age-related decline in physical, socio-psychological and cognitive function that results in extreme vulnerability to stressors. Therefore, this study aimed to elucidate which tests have to be selected to detect frailty in a comprehensive and feasible manner in cardiovascular disease (CVD) patients based on multivariate regression and sensitivity/specificity analyses. Patients (n = 133, mean age 78 ± 7 years) hospitalised for coronary revascularisation or heart failure (HF) were examined using the Fried and Vigorito criteria, together with some additional measurements. Moreover, to examine the association of frailty with 6-month clinical outcomes, hospitalisations and mortality up to 6 months after the initial hospital admission were examined. Some level of frailty was detected in 44% of the patients according to the Vigorito criteria and in 65% of the patients according to the Fried criteria. Frailty could best be detected by a score based on: sex, Mini Nutritional Assessment (MNA), Katz scale, timed up-and-go test (TUG), handgrip strength, Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS-15) and total number of medications. Frailty and specific markers of frailty were significantly associated with mortality and six-month hospitalisations. We thus can conclude that, in patients with CVD, sex, MNA, Katz scale, TUG, handgrip strength, MMSE, GDS-15 and total number of medications play a key role in detecting frailty, assessed by a new time- and cost-efficient test battery.

Validation of the Italian HeartQoL: a short health-related quality of life questionnaire for patients with ischemic heart disease.

The psychometric properties of the core disease-specific 14-item Italian HeartQoL health-related quality of life questionnaire have been evaluated in this study. The Italian version of the HeartQoL, the MacNew questionnaire, and the Hospital Anxiety and Depression Scale were completed by 472 patients (angina, N = 183; myocardial infarction, N = 167; or ischemic heart failure, N = 122) who were recruited in five Italian centers (Florence, Veruno, Turin, Udine, and Naples) between 2015 and 2017. Patients with myocardial infarction reported significantly higher HeartQoL scores than patients with angina or ischemic heart failure. Floor and ceiling effects were always minor on the HeartQoL global scale and physical subscale with moderate ceiling effects on the emotional subscale in the total group and in patients with myocardial infarction. The bifactorial structure of the original HeartQoL questionnaire was confirmed with strong physical, emotional, and global scale H coefficients (> 0.50). The HeartQoL scales demonstrated optimal internal consistency (Cronbach's alpha > 0.84). Convergent and divergent validity were confirmed. Discriminative validity was not confirmed for age, largely confirmed for sex, and fully confirmed for anxiety, depression, and distress. The Italian HeartQoL questionnaire demonstrated adequate key psychometric attributes of internal consistency reliability and validity in Italian-speaking patients with ischemic heart disease.

Inhibitors of Protein Convertase Subtilisin/Kexin 9 (PCSK9) and Acute Coronary Syndrome (ACS): The State-of-the-Art.

Acute Coronary Syndrome (ACS) remains one of the most frequent causes of morbidity and mortality in the world. Although the age- and gender-adjusted incidence of ACS is decreasing, the mortality associated with this condition remains high, especially 1-year after the acute event. Several studies demonstrated that PCSK9 inhibitors therapy determine a significant reduction of major adverse cardiovascular events (MACE) in post-ACS patients, through a process of plaque modification, by intervening in lipid metabolism and platelet aggregation and finally determining an improvement in endothelial function. In the EVACS (Evolocumab in Acute Coronary Syndrome) study, evolocumab allows >90% of patients to achieve LDL-C < 55 mg/dL according to ESC/EAS guidelines compared to 11% of patients who only receive statins. In the EVOPACS (EVOlocumab for Early Reduction of low-density lipoprotein (LDL)-cholesterol Levels in Patients With Acute Coronary Syndromes) study, evolocumab determined LDL levels reduction of 40.7% (95% CI: 45.2 to 36.2; p < 0.001) and allowed 95.7% of patients to achieve LDL levels <55 mg/dL. In ODYSSEY Outcome trial, alirocumab reduced the overall risk of MACE by 15% (HR = 0.85; CI: 0.78-0.93; p = 0.0003), with a reduced risk of all-cause mortality (HR = 0.85; CI: 0.73-0.98: nominal p = 0026), and fewer deaths for coronary heart disease (CHD) compared to the control group (HR = 0.92; CI: 0.76-1.11; p = 0.38). The present review aimed at describing the beneficial effect of PCSK9 inhibitors therapy early after ACS in reducing LDL circulating levels (LDL-C) and the risk of major adverse cardiovascular events, which was very high in the first year and persists higher later after the acute event.

Frailty in Acute and Chronic Coronary Syndrome Patients Entering Cardiac Rehabilitation.

Worldwide population ageing is partly due to advanced standard of care, leading to increased incidence and prevalence of geriatric syndromes such as frailty and disability. Hence, the age at the onset of acute coronary syndromes (ACS) keeps growing as well. Moreover, ageing is a risk factor for both frailty and cardiovascular disease (CVD). Frailty and CVD in the elderly share pathophysiological mechanisms and associated conditions, such as malnutrition, sarcopenia, anemia, polypharmacy and both increased bleeding/thrombotic risk, leading to a negative impact on outcomes. In geriatric populations ACS is associated with an increased frailty degree that has a negative effect on re-hospitalization and mortality outcomes. Frail elderly patients are increasingly referred to cardiac rehabilitation (CR) programs after ACS; however, plans of care must be tailored on individual's clinical complexity in terms of functional capacity, nutritional status and comorbidities, cognitive status, socio-economic support. Completing rehabilitative intervention with a reduced frailty degree, disability prevention, improvement in functional state and quality of life and reduction of re-hospitalization are the goals of CR program. Tools for detecting frailty and guidelines for management of frail elderly patients post-ACS are still debated. This review focused on the need of an early identification of frail patients in elderly with ACS and at elaborating personalized plans of care and secondary prevention in CR setting.

Secondary prevention through comprehensive cardiovascular rehabilitation: From knowledge to implementation. 2020 update. A position paper from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology.

Secondary prevention through comprehensive cardiac rehabilitation has been recognized as the most cost-effective intervention to ensure favourable outcomes across a wide spectrum of cardiovascular disease, reducing cardiovascular mortality, morbidity and disability, and to increase quality of life. The delivery of a comprehensive and 'modern' cardiac rehabilitation programme is mandatory both in the residential and the out-patient setting to ensure expected outcomes. The present position paper aims to update the practical recommendations on the core components and goals of cardiac rehabilitation intervention in different cardiovascular conditions, in order to assist the whole cardiac rehabilitation staff in the design and development of the programmes, and to support healthcare providers, insurers, policy makers and patients in the recognition of the positive nature of cardiac rehabilitation. Starting from the previous position paper published in 2010, this updated document maintains a disease-oriented approach, presenting both well-established and more controversial aspects. Particularly for implementation of the exercise programme, advances in different training modalities were added and new challenging populations were considered. A general table applicable to all cardiovascular conditions and specific tables for each clinical condition have been created for routine practice.

Delphi consensus recommendations on how to provide cardiovascular rehabilitation in the COVID-19 era.

This Delphi consensus by 28 experts from the European Association of Preventive Cardiology (EAPC) provides initial recommendations on how cardiovascular rehabilitation (CR) facilities should modulate their activities in view of the ongoing coronavirus disease 2019 (COVID-19) pandemic. A total number of 150 statements were selected and graded by Likert scale [from -5 (strongly disagree) to +5 (strongly agree)], starting from six open-ended questions on (i) referral criteria, (ii) optimal timing and setting, (iii) core components, (iv) structure-based metrics, (v) process-based metrics, and (vi) quality indicators. Consensus was reached on 58 (39%) statements, 48 'for' and 10 'against' respectively, mainly in the field of referral, core components, and structure of CR activities, in a comprehensive way suitable for managing cardiac COVID-19 patients. Panelists oriented consensus towards maintaining usual activities on traditional patient groups referred to CR, without significant downgrading of intervention in case of COVID-19 as a comorbidity. Moreover, it has been suggested to consider COVID-19 patients as a referral group to CR per se when the viral disease is complicated by acute cardiovascular (CV) events; in these patients, the potential development of COVID-related CV sequelae, as well as of pulmonary arterial hypertension, needs to be focused. This framework might be used to orient organization and operational of CR programmes during the COVID-19 crisis.

Exercise for slowing the progression of atherosclerotic process: effects on inflammatory markers.

Atherosclerosis is a dynamic process driven by all cardiovascular risk factors that can be briefly divided into an early and a late phase. Inflammation is one of the fundamental substrates that initiates the atherosclerotic process in the early stages and promotes and maintains it in the final stages. In the last decades, clinical and experimental data have shown that inflammation is supported by mediators that respond to physical activity. The present review aimed at investigating the effect of physical exercise on inflammatory mediators, both the positive ones that have a proinflammatory effect (interleukin 6, c-reactive protein and tumor necrosis factor α, interferon γ, high-mobility group box-1), and the negative ones which have an anti-inflammatory effect (interleukin 10). Pooled data support the evidence that physical exercise can directly modulate the activity of inflammatory cytokines slowing down or preventing the formation of the atherosclerotic stage.

The core components of cardio-oncology rehabilitation.

The increased efficacy of cancer therapy has resulted in greater cancer survival and increasing number of people with cancer and cardiovascular diseases. The sharing of risk factors, the bidirectional relationship between cancer and cardiovascular diseases and the cardiotoxic effect of chemotherapy and radiotherapy, are the cause of the rapid expansion of cardio-oncology. All strategies to preserve cardiovascular health and mitigate the negative effect of cancer therapy, by reducing the cardiovascular risk, must be pursued to enable the timely and complete delivery of anticancer therapy and to achieve the longest remission of the disease. Comprehensive cardiac rehabilitation is an easy-to-use model, even in cancer care, and is the basis of Cardio-Oncology REhabilitation (CORE), an exercise-based multi-component intervention. In addition, CORE, besides using the rationale and knowledge of cardiac rehabilitation, can leverage the network of cardiac rehabilitation services to offer to cancer patients exercise programs, control of risk factors, psychological support, and nutrition counseling. The core components of CORE will be discussed, describing the beneficial effect on cardiorespiratory fitness, quality of life, psychological and physical well-being, and weight management. Furthermore, particular attention will be paid to how CORE can counterbalance the negative effect of therapies in those at heightened cardiovascular risk after a cancer diagnosis. Barriers for implementation, including personal, family, social and of the health care system barriers for a widespread diffusion of the CORE will also be discussed. Finally, there will be a call-to-action, for randomized clinical trials that can test the impact of CORE, on morbidity and mortality.

Frailty is highly prevalent in specific cardiovascular diseases and females, but significantly worsens prognosis in all affected patients: A systematic review.

Cardiologists are more often confronted with older (>60 years) cardiovascular disease (CVD) patients. These patients have particular needs in clinical care because, for example, of frailty. However, it remains to be established what is the prevalence of frailty in different CVD's and how it relates to mortality. In this systematic review studies were included if they: (i) examined subjects (men and women) aged ≥60 years who suffered from any CVD with or without cardiac surgery, (ii.) examined the presence of frailty with a well-defined frailty tool and (iii.) reported prevalence rates of frailty. From thirty studies comprising 96.841 participants, it is found that 1. Frailty is highly common in older patients with CVD (in particular in females (approximately 1.6 times more than in males), in heart failure (up to 80 % of patients) and aortic valve disease (up to 74 % of patients)), and 2. Frailty is related to a 2.5-3.5-fold elevated mortality risk, even in patients with less severe CVD (e.g. percutaneous coronary intervention). Moreover, there is a lack of consistency on how to assess frailty as up to 20 different tools/assessment batteries are currently used. It is concluded that frailty should be assessed in all older CVD patients in a uniform manner to enhance clinical care and outcomes.

New Ultrasound Technologies for Ischemic Heart Disease Assessment and Monitoring in Cardiac Rehabilitation.

Owing to its ease of application, noninvasive nature, and safety, echocardiography is an essential imaging modality to assess cardiac function in patients affected by ischemic heart disease (IHD). Over the past few decades, we have witnessed a continuous series of evolutions in the ultrasound field that have led to the introduction of innovative echocardiographic modalities which allowed to better understand the morphofunctional abnormalities occurring in cardiovascular diseases. This article offers an overview of some of the newest echocardiographic modalities and their promising application in IHD diagnosis, risk stratification, management, and monitoring after cardiac rehabilitation.

Sacubitril/Valsartan Improves Autonomic Function and Cardiopulmonary Parameters in Patients with Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Heart rate recovery (HRR) is a marker of vagal tone, which is a powerful predictor of mortality in patients with cardiovascular disease. Sacubitril/valsartan (S/V) is a treatment for heart failure with reduced ejection fraction (HFrEF), which impressively impacts cardiovascular outcome. This study aims at evaluating the effects of S/V on HRR and its correlation with cardiopulmonary indexes in HFrEF patients. METHODS: Patients with HFrEF admitted to outpatients' services were screened out for study inclusion. S/V was administered according to guidelines. Up-titration was performed every 4 weeks when tolerated. All patients underwent laboratory measurements, Doppler-echocardiography, and cardiopulmonary exercise stress testing (CPET) at baseline and at 12-month follow-up. RESULTS: Study population consisted of 134 HFrEF patients (87% male, mean age 57.9 ± 9.6 years). At 12-month follow-up, significant improvement in left ventricular ejection fraction (from 28% ± 5.8% to 31.8% ± 7.3%, p < 0.0001), peak exercise oxygen consumption (VO2peak) (from 15.3 ± 3.7 to 17.8 ± 4.2 mL/kg/min, p < 0.0001), the slope of increase in ventilation over carbon dioxide output (VE/VCO2 slope )(from 33.4 ± 6.2 to 30.3 ± 6.5, p < 0.0001), and HRR (from 11.4 ± 9.5 to 17.4 ± 15.1 bpm, p = 0.004) was observed. Changes in HRR were significantly correlated to changes in VE/VCO2slope (r = -0.330; p = 0.003). After adjusting for potential confounding factors, multivariate analysis showed that changes in HRR were significantly associated to changes in VE/VCO2slope (Beta (B) = -0.975, standard error (SE) = 0.364, standardized Beta coefficient (Bstd) = -0.304, p = 0.009). S/V showed significant reduction in exercise oscillatory ventilation (EOV) detection at CPET (28 EOV detected at baseline CPET vs. 9 EOV detected at 12-month follow-up, p < 0.001). HRR at baseline CPET was a significant predictor of EOV at 12-month follow-up (B = -2.065, SE = 0.354, p < 0.001). CONCLUSIONS: In HFrEF patients, S/V therapy improves autonomic function, functional capacity, and ventilation. Whether these findings might translate into beneficial effects on prognosis and outcome remains to be elucidated.