Chiara Lestuzzi

Cardiovascular diseases and cancer are the two primary causes of mortality worldwide. Although traditionally regarded as distinct pathologies, they share numerous pathophysiological mechanisms and risk factors, including chronic inflammation, insulin resistance, obesity, and metabolic dysregulation. Notably, several cancers have been identified as closely linked to cardiovascular diseases, including lung, breast, prostate, and colorectal cancers, as well as hematological malignancies, such as leukemia and lymphoma. Additionally, renal and pancreatic cancers exhibit a significant association with cardiovascular complications, partly due to shared risk factors and the cardiotoxic effects of cancer therapies. Addressing the overlapping risk factors through lifestyle modifications—such as regular physical activity, a balanced diet, and cessation of smoking and alcohol—has proven effective in reducing both CV and oncological morbidity and mortality. Furthermore, even in patients with established cancer, structured interventions targeting physical activity, nutritional optimization, and smoking cessation have been associated with improved outcomes. Beyond lifestyle modifications, pharmacological strategies play a crucial role in the prevention of both diseases. Several cardiovascular medications, including statins, aspirin, beta-blockers, and metformin, exhibit pleiotropic effects that extend beyond their primary indications, demonstrating potential anti-neoplastic properties in preclinical and observational studies. Recently, novel therapeutic agents have garnered attention for their possible cardioprotective and metabolic benefits. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is), initially developed for managing type 2 diabetes, have shown CV and renal protective effects, alongside emerging evidence of their role in modulating cancer-related metabolic pathways. Inclisiran, a small interfering RNA targeting PCSK9, effectively lowers LDL cholesterol and may contribute to reducing CV risk, with potential implications for tumor biology. Additionally, sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor, has revolutionized heart failure management by improving hemodynamic parameters and exerting anti-inflammatory effects that may have broader implications for chronic disease prevention. Given the intricate interplay between CVD and cancer, further research is essential to clarify the exact mechanisms linking these conditions and assessing the potential of CV therapies in cancer prevention. This review aims to examine shared risk factors, consider the role of pharmacological and lifestyle interventions, and emphasize crucial epidemiological and mechanistic insights into the intersection of CV and oncological health.

Doxorubicin is a widely used anticancer agent as a first-line treatment for various tumor types, including sarcomas. Its use is hampered by adverse events, among which is the risk of dose dependence. The potential cardiotoxicity, which increases with higher doses, poses a significant challenge to its safe and effective application. To try to overcome these undesired effects, encapsulation of doxorubicin in liposomes has been proposed. Caelyx and Myocet are different formulations of pegylated (PLD) and non-pegylated liposomal doxorubicin (NPLD), respectively. Both PLD and NPLD have shown similar activity compared with free drugs but with reduced cardiotoxicity. While the hand–foot syndrome exhibits a high occurrence among patients treated with PLD, its frequency is notably reduced in those receiving NPLD. In this prospective, multicenter, one-stage, single-arm phase II trial, we assessed the combination of NPLD and ifosfamide as first-line treatment for advanced/metastatic soft tissue sarcoma (STS). Patients received six cycles of NPLD (50 mg/m²) on day 1 along with ifosfamide (3000 mg/m² on days 1, 2, and 3 with equidose MESNA) administered every 3 weeks. The overall response rate, yielding 40% (95% CI: 0.29–0.51), resulted in statistical significance; the disease control rate stood at 81% (95% CI: 0.73—0.90), while only 16% (95% CI: 0.08–0.24) of patients experienced a progressive disease. These findings indicate that the combination of NPLD and ifosfamide yields a statistically significant response rate in advanced/metastatic STS with limited toxicity.

Cardiac tumors may be primary (either benign or malignant) or secondary (malignant) and are first detected by echocardiography in most cases. The cardiologist often challenges their identification, the differential diagnosis and the best therapeutic approach. Malignant tumors have usually a poor prognosis, which may be significantly improved by appropriate and timely therapies. The echocardiographic aspects of benign and malignant cardiac tumors described in this article, along with a clinical evaluation may orient the differential diagnosis and aid in choosing the further steps useful to define the nature of the mass,

Editorial: Cardiac Tumors: A Challenge in Diagnosis and Therapeutic Approach

Background: Physical activity may increase the risk of cardiotoxicity (myocardial ischemia, major arrhythmias) of 5-Fluorouracil, but this risk has never been investigated for its prodrug capecitabine.Patients and Methods: One hundred and ninety-two consecutive patients undergoing capecitabine chemotherapy from December 1, 2010 through July 31, 2016 were prospectively evaluated. The baseline evaluation included electrocardiography (ECG) and echocardiography (2DE); a follow-up evaluation, including ECG and exercise stress testing (2DE in case of ECG abnormalities), was done after ≥10 days of treatment. Cardiotoxicity was suspected from ischemic ECG changes, new kinetic abnormalities at 2DE, Lown classification ≥2 ventricular arrhythmia, symptomatic arrhythmias, or positive stress test, and confirmed by a negative stress test after capecitabine washout.Results: Cardiotoxicity was diagnosed in 32 patients (16.7%): six at rest and 26 during exercise. All 32 patients had ECG abnormalities: ST-segment changes (24 patients), negative T-waves (2) and/or arrhythmias: ventricular arrhythmias (14 cases), supraventricular tachycardia (2), complete heart block (1). Eight patients had typical symptoms, 6 had atypical symptoms, 1 had syncope, 17 (53%) were asymptomatic. Cardiotoxicity was more common in patients with atypical symptoms during daily life (OR = 15.7) and in those on a therapeutic schedule of 5 days/week (OR = 9.44).Conclusion: Capecitabine cardiotoxicity is frequent, and often elicited by physical effort. Oncologists, cardiologists, and general practitioners should be aware of this risk. Active cardiotoxicity surveillance with ECG (and echocardiogram and/or stress testing in suspected cases) during therapy is recommended.Clinical Trials registration number: CRO-2010-17.

Introduction: Radiotherapy may cause valvular (VHD), pericardial, coronary artery disease (CAD), left ventricular dysfunction (LVD), arrhythmias. The risk of radiation induced heart disease (RIHD) increases over time. The current guidelines suggest a screening for RIHD every 5 years in the long-term survivors who had been treated by chest RT.Methods: We reviewed the clinical and instrumental data of 106 patients diagnosed with RIHD. In one group (Group A: 69 patients) RIHD was diagnosed in an asymptomatic phase through a screening with ECG, echocardiogram and stress test. A second group (37 patients) was seen when RIHD was symptomatic. We compared the characteristics of the two groups at the time of RT, of RIHD detection and at last follow-up.Results: Overall, 64 patients (60%) had CAD (associated to other RIHD in 18); 39 (36.7%) had LVD (isolated in 20); 24 (22.6%) had VHD (isolated in 10 cases). The interval between the last negative test and the diagnosis of moderate or severe RIHD was p < 0.05). At last follow-up, 27 patients had died (12 of cancer, 9 of cardiac causes, 6 of other causes); mean ejection fraction was 60% in group A and 50% in group B (p < 0.01). Patients with ejection fraction ≤ 50% were 14.5% in group A and 40% in group B (p < 0.01).Conclusions: Clinically relevant RIHD become evident at a mean interval of 16 years after RT. The most frequent clinical manifestations are CAD and LVD. RIHD diagnosis in asymptomatic patients may preserve their cardiac function with timely interventions. We suggest -after 10 years from radiotherapy- a screening every 2–3 years.

L’impatto della pandemia COVID-19 sui pazienti affetti da cancro e malattie cardiovascolari ha confermato la particolare vulnerabilità di queste popolazioni. Infatti, non solo si è registrato un rischio più alto di contrarre l’infezione, ma anche un decorso più severo con esiti spesso infausti. Oltre alle dirette conseguenze dell’infezione da SARS-CoV-2, la pandemia ha avuto un impatto enorme sui sistemi sanitari globali. I programmi di screening e gli esami ritenuti non urgenti sono stati rinviati con conseguenti ritardi diagnostici, la sperimentazione clinica ha subito una battuta d’arresto. In cardiologia si è osservato un significativo declino degli accessi per infarto miocardico con sopraslivellamento del tratto ST e un aumento dei casi di infarto a presentazione tardiva con aumento dei tassi di mortalità e di complicanze. I sistemi sanitari devono pertanto essere preparati ad un effetto “rebound” per un aumento relativo di incidenza a breve e medio termine di patologie come scompenso cardiaco, infarto miocardico, aritmie e complicanze cardio- e cerebrovascolari. Le Società Scientifiche si sono attivate per fornire delle raccomandazioni volte a mitigare gli esiti sfavorevoli di questa emergenza pandemica. La cardio-oncologia, disciplina emergente e faro di innovazione nello sviluppo della gestione multispecialistica dei pazienti, ha rapidamente modificato i suoi percorsi clinico-assistenziali e ha implementato protocolli di monitoraggio flessibili che prevedano un impiego mirato dell’imaging cardiaco, un maggiore utilizzo dei biomarcatori e dei sistemi di telemedicina con l’obiettivo di ridurre al minimo il rischio di infezione per operatori e pazienti mantenendo gli standard assistenziali per il trattamento delle malattie oncologiche e cardiovascolari. Scopo di questo position paper ANMCO è quello di valutare le implicazioni della pandemia nello studio e nella gestione dei pazienti cardio-oncologici utilizzando le intuizioni acquisite, al fine di orientare le strategie sia durante la pandemia che nelle fasi future.

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.

Aims: Cardio-oncology has achieved a pivotal role in science, but real world data on its clinical impact are still limited.Methods: A questionnaire was sent out to all cardio-oncology services across Italy (n = 120). The questionnaire was made up of 28 questions divided into four blocks: (A) general information on hospitals and service, (B) the inner organization of cardio-oncology and its relationships with out-of-hospital cardiologists and general practitioners, (C) educational needs and referral guidelines, and (D) activities/specific workload.Results: Ninety-six out of 120 (80%) completed the questionnaire; 9.4% were cancer centers while 90.6% were general hospitals. A cardio-oncology team was present in 56% of the cancer centers and in 20% only of general hospitals, and a cardio-oncology pathway was active in 55% of cancer centers and in just 14% of the general hospitals. Relationships with out-of-hospital cardiologists and general practitioners were lacking. The guidelines of reference were ESC and ANMCO/AIOM. Patients receiving anthracycline chemotherapy underwent scheduled monitoring by means of echocardiography in 58% of cases. Routine use of cardiac damage biomarkers was overall low, ranging from 22 to 33% while the use of global longitudinal strain reached 44%.Conclusions: Italian cardio-oncology showed a growing influence on clinical practice but still has room for improvement. Cardio-oncology teams are still scarce, and the application of dedicated paths is poor. The need for specific training has been highlighted.