Cardio-oncology rehabilitation: are we ready?

Cardio-oncology rehabilitation (CORE) is not only an essential component of cancer rehabilitation but also a pillar of preventive cardio-oncology. Cardio-oncology rehabilitation is a comprehensive model based on a multitargeted approach and its efficacy has been widely documented; when compared with an 'exercise only' programme, comprehensive CORE demonstrates a better outcome. It involves nutritional counselling, psychological support, and cardiovascular (CV) risk assessment, and it is directed to a very demanding population with a heavy burden of CV diseases driven by physical inactivity, cancer therapy-induced metabolic derangements, and cancer therapy-related CV toxicities. Despite its usefulness, CORE is still underused in cancer patients and we are still at the dawning of remote models of rehabilitation (tele-rehabilitation). Not all CORE is created equally: a careful screening procedure to identify patients who will benefit the most from CORE and a multidisciplinary customized approach are mandatory to achieve a better outcome for cancer survivors throughout their cancer journey. The aim of this paper is to provide an updated review of CORE not only for cardiologists dealing with this peculiar population of patients but also for oncologists, primary care providers, patients, and caregivers. This multidisciplinary team should help cancer patients to maintain a healthy and active life before, during, and after cancer treatment, in order to improve quality of life and to fight health inequities.

Italian Association of Hospital Cardiologists Position Paper 'Gender discrepancy: time to implement gender-based clinical management'.

It has been well assessed that women have been widely under-represented in cardiovascular clinical trials. Moreover, a significant discrepancy in pharmacological and interventional strategies has been reported. Therefore, poor outcomes and more significant mortality have been shown in many diseases. Pharmacokinetic and pharmacodynamic differences in drug metabolism have also been described so that effectiveness could be different according to sex. However, awareness about the gender gap remains too scarce. Consequently, gender-specific guidelines are lacking, and the need for a sex-specific approach has become more evident in the last few years. This paper aims to evaluate different therapeutic approaches to managing the most common women's diseases.

Cardio-Oncology in Childhood: State of the Art.

PURPOSE OF REVIEW: Cardio-oncology is an increasingly important field of cardiology that focuses on the detection, monitoring, and treatment of cardiovascular disease (CVD) occurring during and after oncological treatments. The survival rate for childhood cancer patients has dramatically increased thanks to new treatment protocols and cardiovascular (CV) sequelae represent the third most frequent cause of mortality in surviving patients. This study aims to provide a complete and updated review of all the main aspects of cardio-oncology in childhood and to highlight the critical issues. RECENT FINDINGS: The problem of CV complications in childhood cancer survivors raises the need to make an early diagnosis of cardiotoxicity by the new imaging and laboratory techniques in order to intervene promptly and to implement pharmacological strategies and lifestyle changes to reduce or even to prevent cardiac injury. Furthermore, a stratification of CV risk, also including new predisposing factors such as the presence of some genetic mutations, is of paramount importance before undertaking oncological treatments. Besides, a systematic and personalized planning of long-term follow-up is fundamental to ensure a transition from pediatric to adult hospital and to avoid missed or late diagnosis of cardiomyopathy. We reviewed the main risk factors for cardiotoxicity in children, both traditional and emerging ones: the mechanisms of toxicity of both old and new antineoplastic therapies, the techniques for detecting cardiac damage, and the current evidence regarding pharmacological cardioprotection. At the end, we focused our attention on the existing guidelines and strategies about the long-term follow-up of childhood cancer survivors.

ANMCO statement on the use of sodium-glucose cotransporter 2 inhibitors in patients with heart failure: a practical guide for a streamlined implementation.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, dapagliflozin, and empagliflozin, first developed as glucose-lowering agents for the treatment of Type 2 diabetes, have been demonstrated to improve prognosis in patients with heart failure and reduced ejection fraction (HFrEF) regardless of the presence of diabetes. Since these drugs have only recently been included among the four pillars of HFrEF treatment, cardiologists are still unfamiliar with their use in this setting. This article provides an up-to-date practical guide for the initiation and monitoring of patients treated with SGLT2 inhibitors.

Pathophysiology and clinical presentation of paediatric heart failure related to congenital heart disease.

Congenital heart disease (CHD) and cardiomyopathies represent the two most important causes of paediatric heart failure (HF) in developed countries. We made a review of the literature on pathophysiology and clinical presentation of paediatric HF in children with CHD. Two main pathophysiologic models can be identified: the 'over-circulation failure', characterised by signs and symptoms of congestion or hypoperfusion, due respectively to volume or pressure overload, and the 'pump failure'. CONCLUSIONS: The comprehension of the HF pathophysiology in paediatric patients with CHD is of paramount importance for the optimal management and for addressing the best therapeutic choices.

ANMCO POSITION PAPER: cardio-oncology in the COVID era (CO and CO).

The COVID-19 pandemic and its impact on patients with cancer and cardiovascular disease have confirmed the particular vulnerability of these populations. Indeed, not only a higher risk of contracting the infection has been reported but also an increased occurrence of a more severe course and unfavourable outcome. Beyond the direct consequences of COVID-19 infection, the pandemic has an enormous impact on global health systems. Screening programmes and non-urgent tests have been postponed; clinical trials have suffered a setback. Similarly, in the area of cardiology care, a significant decline in STEMI accesses and an increase in cases of late presenting heart attacks with increased mortality and complication rates have been reported. Health care systems must therefore get ready to tackle the 'rebound effect' that will likely show a relative increase in the short- and medium-term incidence of diseases such as heart failure, myocardial infarction, arrhythmias, and cardio- and cerebrovascular complications. Scientific societies are taking action to provide general guidance and recommendations aimed at mitigating the unfavourable outcomes of this pandemic emergency. Cardio-oncology, as an emerging discipline, is more flexible in modulating care pathways and represents a beacon of innovation in the development of multi-specialty patient management. In the era of the COVID-19 pandemic, cardio-oncology has rapidly modified its clinical care pathways and implemented flexible monitoring protocols that include targeted use of cardiac imaging, increased use of biomarkers, and telemedicine systems. The goal of these strategic adjustments is to minimize the risk of infection for providers and patients while maintaining standards of care for the treatment of oncologic and cardiovascular diseases. The aim of this document is to evaluate the impact of the pandemic on the management of cardio-oncologic patients with the-state-of-the-art knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease (COVID-19) in order to optimize medical strategies during and after the pandemic.

Superior mesenteric and renal flow patterns during intra-aortic counterpulsation.

NEW FINDINGS: What is the central question of this study? Visceral ischaemia is one of the most feared complications during use of an intra-aortic balloon pump. Using an animal model, we measured the flows at the abdominal level directly and examined flow patterns to enable investigation of flow patterns during the use of the intra-aortic balloon pump. What is the main finding and its importance? We show that there is a significant balloon-related reduction in superior mesenteric flow in both early and mid-diastole. ABSTRACT: A number of previous studies have shown that blood flow in the visceral arteries is altered during intra-aortic balloon pump (IABP) treatment. We used a porcine model to analyse the pattern of blood flow into the visceral arteries during IABP use. For this purpose, we measured the superior mesenteric, right renal and left renal flows before and during IABP support, using surgically placed flowmeters surrounding these visceral arteries. The superior mesenteric flow significantly decreased in early diastole (P < 0.001) and in mid-diastole (P = 0.003 versus early diastole), whereas in late diastole it increased again (P < 0.001 versus mid-diastole). During systole, the flow was not significantly increased compared with late diastole (P = 0.51), but it was significantly lower than at baseline (both P < 0.001). Flows did not differ between right and left kidneys. Perfusion of either kidney did not change significantly in early diastole (P > 0.05), whereas it decreased significantly in mid-diastole (P < 0.001), rising dramatically in late diastole (P < 0.001) and with an additional slight increase in systole (P = 0.054). This study provides important insights into abdominal flows during intra-aortic pump counterpulsation. Furthermore, it supports the need to rethink the balloon design to avoid visceral ischaemia during circulatory assistance.

Comparison between three different equations for the estimation of glomerular filtration rate in predicting mortality after coronary artery bypass.

BACKGROUND: This study was undertaken to compare the accuracy of chronic kidney disease-epidemiology collaboration (eGFRCKD-EPI) to modification of diet in renal disease (eGFRMDRD) and the Cockcroft-Gault formulas of Creatinine clearance (CCG) equations in predicting post coronary artery bypass grafting (CABG) mortality. METHODS: Data from 4408 patients who underwent isolated CABG over a 11-year period were retrieved from one institutional database. Discriminatory power was assessed using the c-index and comparison between the scores' performance was performed with DeLong, bootstrap, and Venkatraman methods. Calibration was evaluated with calibration curves and associated statistics. RESULTS: The discriminatory power was higher in eGFRCKD-EPI than eGFRMDRD and CCG (Area under Curve [AUC]:0.77, 0.55 and 0.52, respectively). Furthermore, eGFRCKD-EPI performed worse in patients with an eGFR ≤29 ml/min/1.73m2 (AUC: 0.53) while it was not influenced by higher eGFRs, age, and body size. In contrast, the MDRD equation was accurate only in women (calibration statistics p = 0.72), elderly patients (p = 0.53) and subjects with severe impairment of renal function (p = 0.06) whereas CCG was not significantly biased only in patients between 40 and 59 years (p = 0.6) and with eGFR 45-59 ml/min/1.73m2 (p = 0.32) or ≥ 60 ml/min/1.73m2 (p = 0.48). CONCLUSIONS: In general, CKD-EPI gives the best prediction of death after CABG with unsatisfactory accuracy and calibration only in patients with severe kidney disease. In contrast, the CG and MDRD equations were inaccurate in a clinically significant proportion of patients.

Lifestyles and Cardiovascular Prevention in Childhood and Adolescence.

Pathology studies demonstrated that coronary fatty streaks develop early in life and that even more advanced fibrous plaques are present in a proportion of adolescents. The presence and extent of atherosclerosis in children and adolescents can be correlated with the same risk factors present in adults; as well as, childhood levels of these risk factors predict adult cardiovascular diseases. Children are born with ideal cardiovascular health but, unfortunately, most of them develop over time modifiable behavioral risk factors. Achieving sustained lifestyle changes initiated too late in adults is difficult, and pharmacologic risk factor control cannot fully restore a low-risk state. Therefore, it seems eminently reasonable to initiate healthful lifestyle training as early in life, decreasing the prevalence of cardiovascular risk factors to retard atherogenic processes and reduce the future burden of cardiovascular diseases. Many guideline recommendations encourage universal adoption of healthier lifestyles, identification of children with cardiovascular risk factors, and their treatment using targeted lifestyle modification and, rarely, pharmacotherapy. Major gains will likely accrue from public health strategies targeting incorrect diet, physical activity, and cigarette smoking. Individualized strategies, however, will initially focus on the highest risk children such as those with familial hyperlipidaemia, diabetes, hypertension, and obesity. The primary purpose of this article is to provide a broad overview on the long-term cardiovascular effects of risk factors in children and youth and to outline various lines of evidence for the efficacy of primordial and primary prevention in young people, as well as recommendations for population- and individual-level strategies and evidence-based interventions.

Is visceral flow during intra-aortic balloon pumping size or volume dependent?

AIM: We evaluated the influence of intra-aortic balloon size and volume on mesenteric and renal flows. METHODS: Thirty healthy swine underwent 120-minute ligation of the left anterior descending coronary artery followed by 6 hours of reperfusion. Then, they were randomly assigned to the following five groups of animals, with six animals in each group: no intra-aortic balloon pump (IABP), a short 35-mL IABP, a short 40-mL IABP, a long 35-mL IABP and a long 40-mL IABP. Superior mesenteric artery (SMA) and renal flows were measured at baseline (t0), at 2-hour ischemia (t1) and every hour thereafter until 6 hours of reperfusion (from tR1 to tR6). RESULTS: SMA flows increased significantly at tR1 only in the two short IABP groups (p<0.001) and balloon volume did not appear to affect flows which, at any experimental time-point, were comparable using 35 mL or 40 mL balloons (p>0.05). Renal flows appeared to be influenced by balloon length, but not by volume. Indeed, flows in the renal arteries rose during IABP treatment; the increase was significantly higher in the short balloon groups and throughout the whole reperfusion (all, p<0.001). CONCLUSIONS: Changes in visceral perfusion during IABP assistance were significantly related to balloon length, but not to its volume. This could be relevant for the evolution of balloon engineering design in order to reduce the incidence of mesenteric ischemia following IABP. Further research is necessary to confirm these findings.

Surgical ablation in patients undergoing mitral valve surgery: impact of lesion set and surgical techniques on long-term success.

AIMS: To assess the results and impact of lesion set and surgical technique on long-term success of surgical ablation during mitral surgery. METHODS AND RESULTS: The patient population consisted of 685 subjects with persistent and long-standing persistent atrial fibrillation (AF) undergoing cardiac surgery for mitral valve disease as the primary indication and concomitant ablation between January 2003 and January 2012 at three institutions. One hundred and sixty-six underwent unipolar (24.2%), 371 (54.2%) bipolar, and 148 (21.6%) had combined ablation. Median follow-up was 58.4 months (interquartile range 43.3-67.9). To appropriately account for death, a competing risk model was employed to identify predictors of cumulative incidence of recurrent AF among lesion set and surgical techniques. Eight-year freedom from recurrent arrhythmia without antiarrhythmic drugs was 0.60 ± 0.02. Success rate was higher using bipolar radiofrequency (RF) (P < 0.001), after performing mitral isthmus line (P = 0.003) and following the biatrial technique (P < 0.001). Competing risk regression revealed that use of unipolar RF [sub-hazard ratio (SHR) 2.41 (1.52-3.43), P < 0.001], combined unipolar/bipolar ablation [SHR 1.93 (0.89-2.57), P = 0.003] and the absence of right atrial ablation [SHR 2.79 (1.27-3.48), P < 0.001] were predictors of cumulative incidence of long-term recurrence. CONCLUSIONS: Our experience suggests that the use of bipolar clamp improves long-term results in surgical treatment of AF and that right-sided ablation should be routinely added. Randomized studies are necessary to confirm our findings.

How to Manage Beta-Blockade in Older Heart Failure Patients: A Scoping Review.

Beta blockers (BBs) play a crucial role in enhancing the quality of life and extending the survival of patients with heart failure and reduced ejection fraction (HFrEF). Initiating the therapy at low doses and gradually titrating the dose upwards is recommended to ensure therapeutic efficacy while mitigating potential adverse effects. Vigilant monitoring for signs of drug intolerance is necessary, with dose adjustments as required. The management of older HF patients requires a case-centered approach, taking into account individual comorbidities, functional status, and frailty. Older adults, however, are often underrepresented in randomized clinical trials, leading to some uncertainty in management strategies as patients with HF in clinical practice are older than those enrolled in trials. The present article performs a scoping review of the past 25 years of published literature on BBs in older HF patients, focusing on age, outcomes, and tolerability. Twelve studies (eight randomized-controlled and four observational) encompassing 26,426 patients were reviewed. The results indicate that BBs represent a viable treatment for older HFrEF patients, offering benefits in symptom management, cardiac function, and overall outcomes. Their role in HF with preserved EF, however, remains uncertain. Further research is warranted to refine treatment strategies and address specific aspects in older adults, including proper dosing, therapeutic adherence, and tolerability.

Exploring the Perioperative Use of DOACs, off the Beaten Track.

A notable increase in direct oral anticoagulant (DOAC) use has been observed in the last decade. This trend has surpassed the prescription of vitamin K antagonists (VKAs) due to the absence of the need for regular laboratory monitoring and the more favorable characteristics in terms of efficacy and safety. However, it is very common that patients on DOACs need an interventional or surgical procedure, requiring a careful evaluation and a challenging approach. Therefore, perioperative anticoagulation management of patients on DOACs represents a growing concern for clinicians. Indeed, while several surgical interventions require temporary discontinuation of DOACs, other procedures that involve a lower risk of bleeding can be conducted, maintaining a minimal or uninterrupted DOAC strategy. Therefore, a comprehensive evaluation of patient characteristics, including age, susceptibility to stroke, previous bleeding complications, concurrent medications, renal and hepatic function, and other factors, in addition to surgical considerations, is mandatory to establish the optimal discontinuation and resumption timing of DOACs. A multidisciplinary approach is required for managing perioperative anticoagulation in order to establish how to face these circumstances. This narrative review aims to provide physicians with a practical guide for DOAC perioperative management, addressing the most controversial issues.

[Lipoprotein(a): relationships with atherosclerosis and valvular heart disease, and emerging therapies]. / Lipoproteina(a): associazione con la malattia aterosclerotica e valvolare e terapie emergenti.

Lipoprotein(a) [Lp(a)] is a well-established cardiovascular risk factor, whose relationship with atherosclerotic disease has been confirmed by epidemiological, genome-wide association, Mendelian randomization, and meta-analysis studies. This association is determined by its pro-atherogenic, pro-thrombotic and pro-inflammatory properties. Lp(a) is the most common monogenic risk factor for atherosclerosis, with a prevalence of about 1 in 5 people. Recently, its etiopathogenetic relationship with calcific and degenerative valvular heart diseases, particularly with aortic and mitral stenosis, has been suspected. It has not yet been demonstrated whether its reduction translates into a lower risk of cardiovascular events. Up to now, Lp(a) has been considered a non-modifiable risk factor, as current lipid-lowering drugs have limited effects on its levels. New specific lipid-lowering therapies with high efficacy in reducing circulating Lp(a) levels are being investigated in randomized trials; however, the effects of this reduction on cardiovascular outcomes are still being studied.

Coagulation Tests and Reversal Agents in Patients Treated with Oral Anticoagulants: The Challenging Scenarios of Life-Threatening Bleeding and Unplanned Invasive Procedures.

In clinical practice, the number of patients treated with direct oral anticoagulants (DOACs) has consistently increased over the years. Since anticoagulant therapy has been associated with an annual incidence of major bleeding (MB) events of approximately 2% to 3.5%, it is of paramount importance to understand how to manage anticoagulated patients with major or life-threatening bleeding. A considerable number of these patients' conditions necessitate hospitalization, and the administration of reversal agents may be imperative to manage and control bleeding episodes effectively. Importantly, effective strategies for reversing the anticoagulant effects of DOACs have been well recognized. Specifically, idarucizumab has obtained regulatory approval for the reversal of dabigatran, and andexanet alfa has recently been approved for reversing the effects of apixaban or rivaroxaban in patients experiencing life-threatening or uncontrolled bleeding events. Moreover, continuous endeavors are being made to develop supplementary reversal agents. In emergency scenarios where specific reversal agents might not be accessible, non-specific hemostatic agents such as prothrombin complex concentrate can be utilized to neutralize the anticoagulant effects of DOACs. However, it is paramount to emphasize that specific reversal agents, characterized by their efficacy and safety, should be the preferred choice when suitable. Moreover, it is worth noting that adherence to the guidelines for the reversal agents is poor, and there is a notable gap between international recommendations and actual clinical practices in this regard. This narrative review aims to provide physicians with a practical approach to managing specific reversal agents.

Anderson-Fabry Disease: Red Flags for Early Diagnosis of Cardiac Involvement.

Anderson-Fabry disease (AFD) is a lysosome storage disorder resulting from an X-linked inheritance of a mutation in the galactosidase A (GLA) gene encoding for the enzyme alpha-galactosidase A (α-GAL A). This mutation results in a deficiency or absence of α-GAL A activity, with a progressive intracellular deposition of glycosphingolipids leading to organ dysfunction and failure. Cardiac damage starts early in life, often occurring sub-clinically before overt cardiac symptoms. Left ventricular hypertrophy represents a common cardiac manifestation, albeit conduction system impairment, arrhythmias, and valvular abnormalities may also characterize AFD. Even in consideration of pleiotropic manifestation, diagnosis is often challenging. Thus, knowledge of cardiac and extracardiac diagnostic "red flags" is needed to guide a timely diagnosis. Indeed, considering its systemic involvement, a multidisciplinary approach may be helpful in discerning AFD-related cardiac disease. Beyond clinical pearls, a practical approach to assist clinicians in diagnosing AFD includes optimal management of biochemical tests, genetic tests, and cardiac biopsy. We extensively reviewed the current literature on AFD cardiomyopathy, focusing on cardiac "red flags" that may represent key diagnostic tools to establish a timely diagnosis. Furthermore, clinical findings to identify patients at higher risk of sudden death are also highlighted.

[ANMCO Position paper: States General 2023 - Digital medicine in cardiology: evidence and state of progress in Italy]. / Position paper ANMCO: Stati Generali 2023 ­ La medicina digitale in cardiologia: evidenze e stato di avanzamento in Italia.

Technological innovation provides easily accessible tools capable of simplifying healthcare processes. Notably, digital technology application in the cardiology field can improve prognosis, reduce costs, and lead to an overall improvement in healthcare. The digitization of health data, with the use of electronic health records and of electronic health files in Italy, represents one of the fields of application of digital technologies in medicine. The 2023 States General of the Italian Association of Hospital Cardiologists (ANMCO) provided an opportunity to focus attention on the potential benefits and critical issues associated with the implementation of the aforementioned digital tools, artificial intelligence, and telecardiology. This document summarizes key aspects that emerged during the event.

Heart Failure with Preserved Ejection Fraction: How to Deal with This Chameleon.

Heart failure with preserved ejection fraction (HFpEF) is characterized by a notable heterogeneity in both phenotypic and pathophysiological features, with a growing incidence due to the increase in median age and comorbidities such as obesity, arterial hypertension, and cardiometabolic disease. In recent decades, the development of new pharmacological and non-pharmacological options has significantly impacted outcomes, improving clinical status and reducing mortality. Moreover, a more personalized and accurate therapeutic management has been demonstrated to enhance the quality of life, diminish hospitalizations, and improve overall survival. Therefore, assessing the peculiarities of patients with HFpEF is crucial in order to obtain a better understanding of this disorder. Importantly, comorbidities have been shown to influence symptoms and prognosis, and, consequently, they should be carefully addressed. In this sense, it is mandatory to join forces with a multidisciplinary team in order to achieve high-quality care. However, HFpEF remains largely under-recognized and under-treated in clinical practice, and the diagnostic and therapeutic management of these patients remains challenging. The aim of this paper is to articulate a pragmatic approach for patients with HFpEF focusing on the etiology, diagnosis, and treatment of HFpEF.

[ANMCO Position paper in collaboration with ITACARE-P: Cardio-oncology rehabilitation. Are we ready?] / Position paper ANMCO in collaborazione con ITACARE-P: Riabilitazione cardio-oncologica. "Are we ready?".

Cardio-oncology rehabilitation (CORE) is not only an essential component of cancer rehabilitation, but also a pillar of preventive cardio-oncology. CORE is a comprehensive model based on a multitargeted approach and its efficacy has been widely documented; when compared to an "exercise only" program, comprehensive CORE demonstrates a better outcome. It involves nutritional counseling, psychological support and cardiovascular risk assessment, and it is directed to a very demanding population with a heavy burden of cardiovascular diseases driven by physical inactivity, cancer therapy-induced metabolic derangements and cancer therapy-related cardiovascular toxicities. Despite its usefulness, CORE is still underused in cancer patients and we are still at the dawning of remote models of rehabilitation (telerehabilitation). Not all cardio-oncology rehabilitation is created equal: a careful screening procedure to identify patients who will benefit the most from CORE and a multidisciplinary customized approach are mandatory to achieve a better outcome for cancer survivors throughout their cancer journey.The aim of this position paper is to provide an updated review of CORE not only for cardiologists dealing with this peculiar patient population, but also for oncologists, primary care providers, patients and caregivers. This multidisciplinary team should help cancer patients to maintain a healthy and active life before, during and after cancer treatment, in order to improve quality of life and to fight health inequities.

[Multidistrict atherosclerotic disease: epidemiological and clinical framework]. / Malattia aterosclerotica polidistrettuale: inquadramento epidemiologico e clinico.

Atherosclerosis is a systemic disease that can involve different arterial districts. Traditionally, the focus of cardiologists has been on the diagnosis and treatment of atherosclerotic coronary artery disease (CAD). However, atherosclerosis localization in other districts is increasingly common and is associated with an increased risk of CAD and, more generally, of adverse cardiovascular events. Although the term peripheral arterial disease (PAD) commonly refers to the localization of atherosclerotic disease in the arterial districts of the lower limbs, in this document, in accordance with the European Society of Cardiology guidelines, the term PAD will be used for all the locations of atherosclerotic disease excluding coronary and aortic ones. The aim of this review is to report updated data on PAD epidemiology, with particular attention to the prevalence and its prognostic impact on patients with CAD. Furthermore, the key points for an appropriate diagnostic framework and a correct pharmacological therapeutic approach are summarized, while surgical/interventional treatment goes beyond the scope of this review.