"Inherited cardiovascular disease mindset" can identify concealed inherited conditions at cardio-oncology evaluation: An opportunistic screening.

INTRODUCTION: Baseline cardiovascular (CV) risk stratification is recommended in all cancer patients. Integrating all clinical information (personal/family history, ECG and echocardiogram) can properly identify high-risk patients. We aimed to evaluate the concealed inherited CV conditions detected in mandatory CV screening performed at a Cardio-Oncology Unit. METHODS: retrospective study of all consecutive cancer patients referred to the Cardio-Oncology Unit for CV evaluation (2020-2023). Inherited CV conditions diagnosis and genetic testing was performed according to guidelines. RESULTS: 1984 cancer patients underwent CV screening. Sanger sequencing was indicated in 1 patient, excluding the genetic family disease. NGS sequencing was performed in 11 cancer patients with normal left ventricular ejection fraction (LVEF): 2 due to aortic syndrome evaluation (identifying 1 vascular Ehrler-Danlos syndrome due to COL3A1 p.Arg242Ter), 4 channelopathies (2 Long QT syndrome and 2 Brugada's), 4 hypertrophic cardiomyopathies and 1 non-dilated left ventricular cardiomyopathy (NDLVC). Among the 12 patients with reduced LVEF, one was diagnosed with NDLVC, and chemotherapy-induced dilated cardiomyopathy was only ascribable in 3 of them. CONCLUSION: Integrating clinical information at mandatory baseline CV toxicity risk cardio-oncology evaluation, can identify high-risk cancer patients with concealed inherited conditions. Keeping an "inherited cardiovascular disease-oriented mindset" to implement opportunist screenings is encouraged.

Ischaemic heart disease in patients with cancer.

Cardiologists are encountering a growing number of cancer patients with ischaemic heart disease (IHD). Several factors account for the interrelationship between these two conditions, in addition to improving survival rates in the cancer population. Established cardiovascular (CV) risk factors, such as hypercholesterolaemia and obesity, predispose to both IHD and cancer, through specific mechanisms and via low-grade, systemic inflammation. This latter is also fuelled by clonal haematopoiesis of indeterminate potential. Furthermore, experimental work indicates that IHD and cancer can promote one another, and the CV or metabolic toxicity of anticancer therapies can lead to IHD. The connections between IHD and cancer are reinforced by social determinants of health, non-medical factors that modify health outcomes and comprise individual and societal domains, including economic stability, educational and healthcare access and quality, neighbourhood and built environment, and social and community context. Management of IHD in cancer patients is often challenging, due to atypical presentation, increased bleeding and ischaemic risk, and worse outcomes as compared to patients without cancer. The decision to proceed with coronary revascularization and the choice of antithrombotic therapy can be difficult, particularly in patients with chronic coronary syndromes, necessitating multidisciplinary discussion that considers both general guidelines and specific features on a case by case basis. Randomized controlled trial evidence in cancer patients is very limited and there is urgent need for more data to inform clinical practice. Therefore, coexistence of IHD and cancer raises important scientific and practical questions that call for collaborative efforts from the cardio-oncology, cardiology, and oncology communities.

The BALTO Registry: Long-term results of percutaneous BALloon pericardioTomy in oncological patients.

OBJECTIVES: The aim of this study was to analyze the efficacy and safety of percutaneous balloon pericardiotomy (PBP) in oncological patients who present with a malignant pericardial effusion (MPE). BACKGROUND: The use of PBP as a treatment for MPE is not standardized due to the limited evidence. Furthermore, the performance of a second PBP for a recurrence after a first procedure is controversial. METHODS: The BALTO Registry (BALloon pericardioTomy in Oncological patients) is a prospective, single-center, observational registry that includes consecutive PBP performed for MPE from October 2007 to February 2022. Clinical and procedural, characteristics, as well as clinical outcome were analyzed. RESULTS: Seventy-six PBP were performed in 61 patients (65% female). Mean age was of 66.4 ± 11.2 years. In 15 cases, a second PBP procedure was performed due to recurrence despite the first PBP. The procedure could be performed effectively in all cases with only two serious complications. Ninety-five percent of cases were discharged alive from the hospital. During a median follow-up of 6.3 months (interquartile range [IQR], 0.9-10.8), MPE recurred in 24.5% cases although no recurrences were reported after the second procedure. No evidence of malignant pleural effusion developed on follow-up. The median overall survival time was 5.8 months (IQR, 0.8-10.2) and the time to recurrence after the first PBP was 2.4 months (IQR, 0.7-4.5). CONCLUSIONS: PBP is a safe and effective treatment for MPE. It could be considered an acceptable therapy in most MPE, even in those who recur after a first procedure.

A review of the pathophysiological mechanisms of doxorubicin-induced cardiotoxicity and aging.

The population of cancer survivors is rapidly increasing due to improving healthcare. However, cancer therapies often have long-term side effects. One example is cancer therapy-related cardiac dysfunction (CTRCD) caused by doxorubicin: up to 9% of the cancer patients treated with this drug develop heart failure at a later stage. In recent years, doxorubicin-induced cardiotoxicity has been associated with an accelerated aging phenotype and cellular senescence in the heart. In this review we explain the evidence of an accelerated aging phenotype in the doxorubicin-treated heart by comparing it to healthy aged hearts, and shed light on treatment strategies that are proposed in pre-clinical settings. We will discuss the accelerated aging phenotype and the impact it could have in the clinic and future research.

Cardiovascular Risk in Patients with Hematological Malignancies: A Systematic Review and Meta-Analysis.

Patients with hematologic malignancies (HMs) are at risk of future cardiovascular (CV) events. We therefore conducted a systematic review and meta-analysis to quantify their risk of future CV events. We searched Medline and EMBASE databases from inception until January 31, 2023 for relevant articles using a combination of keywords and medical subject headings. Studies examining CV outcomes in patients with HM versus controls without HM were included. The outcomes of interest included acute myocardial infarction (AMI), heart failure (HF), and stroke. The outcomes were expressed as hazard ratios (HRs) and their 95% confidence intervals (CIs). This study is registered with PROSPERO at CRD42022307814. A total of 15 studies involving 1,960,144 cases (178,602 patients with HM and 1,781,212 controls) were included in the quantitative analysis. A total of 10 studies examined the risk of AMI, 5 examined HF, and 11 examined stroke. Compared with the control group, the HRs for HM for AMI, HF, and stroke were 1.65 (95% CI 1.29 to 2.09, p <0.001), 4.82 (95% CI 3.72 to 6.25, p <0.001), and 1.60 (95% CI 1.30 to 1.97, p <0.001), respectively. The sensitivity analysis of stroke risk based on lymphoma type showed an increased risk of stroke in patients with non-Hodgkin lymphoma compared with controls (HR 1.31, 95% CI 1.04 to 1.64, p = 0.03) but no significant difference for Hodgkin lymphoma (HR 1.67, 95% CI 0.86 to 3.23, p = 0.08). Patients with HM are at increased risk of future AMI, HF, and stroke, and these findings suggest that CV care of patients with HM should be considered as a growing priority.

Severe cardiac events induced by combination immunotherapy in patients with cancer: a meta-analysis.

Introduction: The use of combined immunotherapy could increase non-severe and severe cardiac events in patients with cancer. To examine the occurrence of severe cardiac adverse events of combined immunotherapy compared to single immunotherapy, we analysed 4 electronic databases from inception to August 2021. Material and methods: We selected randomized controlled trials (RCTs) comparing combined versus single immunotherapy, for the treatment of melanoma, oesophagogastric cancer, renal cell carcinoma, and non-small cell lung cancer. Pre-defined combined immunotherapy included monoclonal antibodies against programmed cell death 1 (PD-1 inhibitors) plus against cytotoxic T lymphocyte antigen 4 (CTLA-4 inhibitors) or against programmed cell death ligand 1 (PD-L1 inhibitors) plus CTLA-4 inhibitors. The pooled risk ratios (RR) with their 95% confidence intervals (CI) were estimated using a random-effects model. Results: Four RCTs involving 1581 patients were included, with a follow-up time between 18 and 39 months. The use of combined immunotherapy in comparison with single immunotherapy was not associated with an increased risk of severe cardiac adverse events: acute coronary syndromes (RR = 1.76, 95% CI: 0.29-10.83, very low certainty of evidence (CoE)), myocardial infarction (RR = 3.93, 95% CI: 0.44-35.39, very low CoE), heart failure (RR = 2.99, 95% CI: 0.61-14.79, very low CoE), and atrial fibrillation (RR = 2.26, 95% CI: 0.62-8.16, very low CoE). Conclusions: Our meta-analysis shows that the risk of severe cardiac adverse events with combined immunotherapy seems similar to single immunotherapy, but the evidence is very uncertain. Therefore, more RCTs with longer follow-ups and adequately powered to assess cardiac adverse events are needed to confirm these findings.

European Society of Cardiology Core Curriculum for cardio-oncology.

Cardio-oncology is a rapidly growing field of cardiovascular (CV) medicine that has resulted from the continuously increasing clinical demand for specialized CV evaluation, prevention and management of patients suffering or surviving from malignant diseases. Dealing with CV disease in patients with cancer requires special knowledge beyond that included in the general core curriculum for cardiology. Therefore, the European Society of Cardiology (ESC) has developed a special core curriculum for cardio-oncology, a consensus document that defines the level of experience and knowledge required for cardiologists in this particular field. It is structured into 8 chapters, including (i) principles of cancer biology and therapy; (ii) forms and definitions of cancer therapy-related cardiovascular toxicity (CTR-CVT); (iii) risk stratification, prevention and monitoring protocols for CTR-CVT; (iv) diagnosis and management of CV disease in patients with cancer; (v) long-term survivorship programmes and cardio-oncology rehabilitation; (vi) multidisciplinary team management of special populations; (vii) organization of cardio-oncology services; (viii) research in cardio-oncology. The core curriculum aims at promoting standardization and harmonization of training and evaluation in cardio-oncology, while it further provides the ground for an ESC certification programme designed to recognize the competencies of certified specialists.

Social disparities in cardiovascular mortality of patients with cancer in the USA between 1999 and 2019.

Background: Temporal trends of the impact of social determinants on cardiovascular outcomes of cancer patients has not been previously studied. Objectives: This study examined social disparities in cardiovascular mortality of people with and without cancer in the US population between 1999 and 2019. Methods: Primary cardiovascular deaths were identified from the Multiple Cause of Death database and grouped by cancer status. The cancer cohort was subcategorized into breast, lung, prostate, colorectal, and haematological. The number of cardiovascular deaths, crude cardiovascular mortality rate, cardiovascular age-adjusted mortality rate (AAMR), and percentage change in cardiovascular AAMR were calculated by cancer status and cancer type, and stratified by sex, race, ethnicity, and urban-rural setting. Results: 17.9 million cardiovascular deaths were analysed. Of these, 572,222 occurred in patients with a record of cancer. The cancer cohort were older and included more men and White racial groups. Regardless of cancer status, cardiovascular AAMR was higher in men, rural settings, and Black or African American races. Cardiovascular AAMR declined over time, with greater reduction in those with cancer (-51.6% vs -38.3%); the greatest reductions were in colorectal (-68.4%), prostate (-60.0%), and breast (-58.8%) cancers. Sex, race, and ethnic disparities reduced over time, with greater narrowing in the cancer cohort. There was increase in urban-rural disparities, which appeared greater in those with cancer. Conclusions: While most social disparities narrowed over time, urban-rural disparities widened, with greater increase in those with cancer. Healthcare plans should incorporate strategies for reduction of health inequality equitable access to cardio-oncology services.

Global Cardio Oncology Registry (G-COR): Registry Design, Primary Objectives, and Future Perspectives of a Multicenter Global Initiative.

BACKGROUND: Global collaboration in cardio-oncology is needed to understand the prevalence of cancer therapy-related cardiovascular toxicity in different risk groups, practice settings, and geographic locations. There are limited data on the socioeconomic and racial/ethnic disparities that may impact access to care and outcomes. To address these gaps, we established the Global Cardio-Oncology Registry, a multinational, multicenter prospective registry. METHODS: We assembled cardiologists and oncologists from academic and community settings to collaborate in the first Global Cardio-Oncology Registry. Subsequently, a survey for site resources, demographics, and intention to participate was conducted. We designed an online data platform to facilitate this global initiative. RESULTS: A total of 119 sites responded to an online questionnaire on their practices and main goals of the registry: 49 US sites from 23 states and 70 international sites from 5 continents indicated a willingness to participate in the Global Cardio-Oncology Registry. Sites were more commonly led by cardiologists (85/119; 72%) and were more often university/teaching (81/119; 68%) than community based (38/119; 32%). The average number of cardio-oncology patients treated per month was 80 per site. The top 3 Global Cardio-Oncology Registry priorities in cardio-oncology care were breast cancer, hematologic malignancies, and patients treated with immune checkpoint inhibitors. Executive and scientific committees and specific committees were established. A pilot phase for breast cancer using Research Electronic Data Capture Cloud platform recently started patient enrollment. CONCLUSIONS: We present the structure for a global collaboration. Information derived from the Global Cardio-Oncology Registry will help understand the risk factors impacting cancer therapy-related cardiovascular toxicity in different geographic locations and therefore contribute to reduce access gaps in cardio-oncology care. Risk calculators will be prospectively derived and validated.

Immune Checkpoint Inhibitor-Related Stress Cardiomyopathy: Differential Diagnosis and Key Role of Cardiac Imaging.

A 76-year-old man with stage IV urothelial carcinoma who was receiving atezolizumab presented with dyspnea, elevated cardiac biomarkers, new negative T waves, and left ventricular apical akinesia. Coronary angiography results were normal. Immune checkpoint inhibitor-related myocarditis was suspected, and high-dose corticosteroid treatment was started. Cardiac magnetic resonance showed apical edema, suggesting stress cardiomyopathy. (Level of Difficulty: Beginner.).

Burden and prognostic impact of cardiovascular disease in patients with cancer.

The number of patients at the intersection of cancer and cardiovascular disease (CVD) is increasing, reflecting ageing global populations, rising burden of shared cardiometabolic risk factors, and improved cancer survival. Many cancer treatments carry a risk of cardiotoxicity. Baseline cardiovascular risk assessment is recommended in all patients with cancer and requires consideration of individual patient risk and the cardiotoxicity profile of proposed anticancer therapies. Patients with pre-existing CVD are potentially at high or very high risk of cancer-therapy related cardiovascular toxicity. The detection of pre-existing CVD should prompt cardiac optimisation and planning of surveillance during cancer treatment. In patients with severe CVD, the risk of certain cancer therapies may be prohibitively high. Such decisions require multidisciplinary discussion with consideration of alternative anti-cancer therapies, risk-benefit assessment, and patient preference. Current practice is primarily guided by expert opinion and data from select clinical cohorts. There is need for development of a stronger evidence base to guide clinical practice in cardio-oncology. The establishment of multicentre international registries and national-level healthcare data linkage projects are important steps towards facilitating enrichment of cardio-oncology research programmes. In this narrative review, we consider epidemiological trends of cancer and CVD comorbidities and the impact of their co-occurrence on clinical outcomes, current approach to supporting cancer patients with pre-existing CVD and gaps in existing knowledge.

Cardiovascular toxicity of checkpoint inhibitors: review of associated toxicity and design of the Spanish Immunotherapy Registry of Cardiovascular Toxicity.

Immune checkpoint inhibitors (ICI) have changed the prognosis of many tumors. However, concerning associated cardiotoxicity has been reported. Little is known about the real-life incidence-specific surveillance protocols or the translational correlation between the underlying mechanisms and the clinical presentation of ICI-induced cardiotoxicity. The lack of data from prospective studies led us to review the current knowledge and to present the creation of the Spanish Immunotherapy Registry of Cardiovascular Toxicity (SIR-CVT), a prospective registry of patients receiving ICI that aims to examine the role of hsa-miR-Chr8:96, (a specific serum biomarker of myocarditis) in the early diagnosis of ICI-induced myocarditis. An exhaustive prospective cardiac imaging study will be performed before and during the first 12 months of treatment. The correlation between clinical, imaging, and immunologic parameters may improve our understanding of ICI-induced cardiotoxicity and enable simpler surveillance protocols. We assess ICI-induced cardiovascular toxicity and describe the rationale of the SIR-CVT.

Outcomes of ST elevation myocardial infarction in patients with cancer: a nationwide study.

AIMS: To assess processes of care and clinical outcomes in cancer patients with ST elevation myocardial infarction (STEMI) according to cancer type. METHODS AND RESULTS: This is a national population-based study of patients admitted with STEMI in the UK between January 2005 and March 2019. Data were obtained from the National Heart Attack Myocardial Infarction National Audit Project (MINAP) registry and the Hospital Episode Statistics registry. We identified 353 448 STEMI-indexed admissions between 2005 and 2019. Of those, 8581 (2.4%) had active cancer. Prostate cancer (29% of STEMI patients with cancer) was the most common cancer followed by haematologic malignancies (14%) and lung cancer (13%). Cancer patients were less likely to receive invasive coronary revascularization (60.0% vs. 71.6%, P < 0.001] and had higher in-hospital death [odd ratio (OR) 1.39, 95% confidence interval (CI) 1.25-1.54] and bleeding (OR 1.23, 95% CI 1.03-1.46). Cancer patients had higher mortality at 30 days (HR 2.39, 95% CI 2.19-2.62) and 1 year (HR 3.73, 95% CI 3.58-3.89). Lung cancer was the cancer associated with the highest risk of death in the hospital (OR 1.75, 95% CI 1.39-2.22) and at 1 year (OR 8.08, 95% CI 7.44-8.78). Colon cancer (OR 1.98, 95% CI 1.24-3.14) was the main cancer associated with major bleeding. All common cancer types were associated with higher mortality at 1 year. Cardiovascular death (62%) was the main cause of death in the first 30 days, while cancer (52%) was the main cause of death within 1 year. CONCLUSION: STEMI patients with cancer have a higher risk of short- and long-term mortality, particularly lung cancer. Colon cancer is the main cancer associated with major bleeding. Cardiovascular disease was the main cause of death in the first month, whereas cancer was the main cause of death within 1 year.