Arterial inflammation on [18F]FDG PET/CT in melanoma patients treated with and without immune checkpoint inhibitors: CHECK-FLAME I.

BACKGROUND AND AIMS: Immune checkpoint inhibitors (ICIs) revolutionized cancer treatment. However, ICIs may increase the immune response to non-tumor cells, possibly resulting in increased arterial inflammation, raising the risk of atherosclerotic events. Nevertheless, malignancies may induce a pro-inflammatory state and the association between ICIs and arterial inflammation remains to be clarified. This study aims to assess differences in increase in arterial inflammation between patients with advanced melanoma treated with ICIs compared to a control group without ICIs. METHODS: Patients with advanced melanoma who underwent [18F]FDG PET/CT scans at baseline, 6 months (T1) and 18 months (T2) were included in this retrospective observational study. Arterial inflammation was evaluated in eight segments by calculating the target-to-background ratio (TBR). The primary study outcome was the difference in increase in mean TBRmax between patients treated with and without ICIs. RESULTS: We included 132 patients of whom 72.7 % were treated with ICIs. After exclusion for the use of anti-inflammatory medication, patients treated with ICIs showed a significant increase in mean TBRmax between baseline and T1 from 1.29 ± 0.12 to 1.33 ± 0.13 (p = 0.017), while in the control group, no change in mean TBRmax (1.30 ± 0.12 to 1.28 ± 0.10, p = 0.22) was observed (p = 0.027). During longer follow-up, mean TBRmax remained stable in both groups. Arterial inflammation increased significantly after ICI therapy in patients without active inflammation (p < 0.001) and in patients without calcifications (p = 0.013). CONCLUSIONS: A significant increase in arterial inflammation as measured on [18F]FDG PET/CT was observed in patients with advanced melanoma treated with ICIs only in the first six months after initiation of therapy, whereas no changes were observed in the control group. Moreover, arterial inflammation was mainly increased in patients without pre-existing inflammatory activity and with non-calcified lesions.

Reversing Immune Checkpoint Inhibitor-Associated Cardiotoxicity via Bioorthogonal Metabolic Engineering-Driven Extracellular Vesicle Redirecting.

The cardiotoxicity induced by immune checkpoint inhibitors (ICIs) is associated with high mortality rates. T cells play an important role in ICI-induced cardiac injury. The inhibition of local T-cell activity is considered an effective strategy for alleviating ICI-related cardiotoxicity. Tumor-derived extracellular vesicles (EVs) contribute to immunosuppression via PD-L1 overexpression. In this study, a bioorthogonal metabolic engineering-driven EV redirecting (Biomeder) strategy for in situ engineered EVs with myocardial-targeting peptides is developed. Accumulated tumor-derived EV (TuEVs) reverses the immune environment in the heart by increasing PD-L1 levels in cardiomyocytes and/or by directly inhibiting T-cell activity. More importantly, it is found that the redirection of TuEVs further disrupts immunosuppression in tumors, which facilitates anti-tumor activity. Thus, redirecting TuEVs to the heart simultaneously enhances the antitumor efficacy and safety of ICI-based therapy. Furthermore, the Biomeder strategy is successfully expanded to prevent ICI-induced type 1 diabetes. This Biomeder technique is a universal method for the treatment of various ICI-related adverse events.

Cardiac wasting in patients with cancer.

Patients with cancer face a significant risk of cardiovascular death, regardless of time since cancer diagnosis. Elderly patients are particularly more susceptible as cancer-associated cardiac complications present in advanced stage cancer. These patients may often present with symptoms observed in chronic heart failure (HF). Cardiac wasting, commonly observed in these patients, is a multifaceted syndrome characterized by systemic metabolic alterations and inflammatory processes that specifically affect cardiac function and structure. Experimental and clinical studies have demonstrated that cancer-associated cardiac wasting is linked with cardiac atrophy and altered cardiac morphology, which impairs cardiac function, particularly pertaining to the left ventricle. Therefore, this review aims to present a summary of epidemiologic data and pathophysiological mechanisms of cardiac wasting due to cancer, and future directions in this field.

Complete Heart Block in a Patient Undergoing Combination Immune Checkpoint Inhibitor Therapy.

Combination immune checkpoint inhibitor (ICI) therapy is an emerging chemotherapy strategy for patients with solid tumor malignancies. Cardiotoxicity is a rare adverse effect of ICI therapy, most commonly presenting as acute myocarditis and, less frequently, as significant conduction abnormalities. We present a unique case of a 68-year-old female with urothelial cancer who developed shortness of breath and chest pain one week after receiving combination ICI therapy with ipilimumab and nivolumab. Biomarkers were elevated, including high-sensitivity troponin to 14,000 ng/L and creatine phosphokinase to 20,000 U/L. Due to suspicion of acute ICI-related myocarditis, a transthoracic echocardiogram (TTE) was obtained and demonstrated preserved ejection fraction (EF). Pulse-dose methylprednisolone therapy was initiated. However, the patient's clinical status continued to decline, and she developed bradycardia due to a complete heart block (CHB). This was initially treated with a dopamine infusion, but due to hypotension and hemodynamic instability, a transvenous pacemaker was placed. She continued to decline from a heart failure standpoint and developed acute hypoxic respiratory failure, requiring intubation due to pulmonary edema. A repeat TTE acquired three days following the initial echocardiogram demonstrated a newly reduced EF of 30%-35%. Additional anti-inflammatory agents were administered, including mycophenolate, infliximab, and anti-thymocyte globulin, with little improvement in clinical status. Unfortunately, she rapidly deteriorated, resulting in pulseless electrical activity (PEA) arrest and circulatory death. The autopsy revealed severe biventricular myocarditis with partial involvement of the atrioventricular node, consistent with her clinical syndrome of acute heart failure and CHB. A literature review demonstrated very few cases of ICI-related CHB. This case highlights a rare instance of atrioventricular dissociation in a patient with cardiotoxicity due to combination ICI therapy.

The Role of Nursing in the Delivery of Cardio-Oncology.

OPINION STATEMENT: Nurses are the "heart of patient care" and in the forefront of the health care delivery for cardio-oncology patients. Nurses play a critical central role in maximizing longitudinal health of cancer patients and survivors through the prevention of cardiovascular complications throughout the patient's cancer care journey. Nurses function in a variety of roles such as nurse clinicians, advanced practice nurses (APNs)or nurse practitioners (NPs), patient educators, managers, nurse navigators or nurse researchers. The role of nurses, particularly the advanced practice nurses as key members in delivering cardio-oncology care is evolving. However, despite the rapidly increasing growth of cardio oncology programs globally, a pivotal need remains to develop and provide formalized training programs for nurses, NPs and APNs. At present, no formal academic cardio-oncology nurse training program or certification exists. There is clearly more work to be done on the role of nurses in cardio-oncology care. As cardio-oncology evolves to become a key specialty with dedicated services being established across the globe, the role of the nurse in delivering this service is critical and a concerted collaborative approach between the two distinct specialties of cardiology and oncology needs to ensure the nursing workforce is educationally prepared and confident to treat and manage cardio-oncology patients.

Radiation Oncology Opinions and Practice on Cardiotoxicity in Lung Cancer: A Cross-sectional Study by the International Cardio-oncology Society.

AIMS: Symptomatic radiation cardiotoxicity affects up to 30% patients with lung cancer and several heart substructure doses are associated with reduced overall survival. A greater focus on minimising cardiotoxicity is now possible due to advancements in radiotherapy technology and the new discipline of cardio-oncology, but uptake of emerging data has not been ascertained. A global cross-sectional analysis of Radiation Oncologists who treat lung cancer was therefore conducted by the International Cardio-Oncology Society in order to establish the impact of recently published literature and guidelines on practice. MATERIALS AND METHODS: A bespoke questionnaire was designed following an extensive review of the literature and from recurring relevant themes presented at Radiation Oncology and Cardio-Oncology research meetings. Six question domains were retained following consensus discussions among the investigators, comprising 55 multiple choice stems: guidelines, cardiovascular assessment, cardiology investigations, radiotherapy planning strategies, primary prevention prescribing and local cardio-oncology service access. An invitation was sent to all Radiation Oncologists registered with ICOS and to Radiation Oncology colleagues of the investigators. RESULTS: In total 118 participants were recruited and 92% were consultant physicians. The ICOS 2021 expert consensus statement was rated as the most useful position paper, followed by the joint ESC-ESTRO 2022 guideline. The majority (80%) of participants indicated that a detailed cardiovascular history was advisable. Although 69% of respondents deemed the availability of cardiac substructure auto-segmentation to be very/quite important, it was implemented by only a few, with the most common being the left anterior descending coronary artery V15. A distinct cardio-oncology service was available to 39% participants, while the remainder utilised general cardiology services. CONCLUSION: The uptake of recent guidelines on cardiovascular optimisation is good, but access to cardiology investigations and consultations, and auto-segmentation, represent barriers to modifying radiotherapy practices in lung cancer to reduce the risk of radiation cardiotoxicity.

Breast cancer and cardiovascular health.

Modern cancer therapies greatly improve clinical outcomes for both early and advanced breast cancer patients. However, these advances have raised concerns about potential short- and long-term toxicities, including cardiovascular toxicities. Therefore, understanding the common risk factors and underlying pathophysiological mechanisms contributing to cardiovascular toxicity is essential to ensure best breast cancer outcomes. While cardio-oncology has emerged as a sub-speciality to address these challenges, it is essential that all cardiologists recognize and understand the cardiovascular consequences of cancer therapy. This review aims to provide a comprehensive overview of the potential adverse cardiovascular effects associated with modern breast cancer therapies. A preventive, diagnostic, and therapeutic workflow to minimize the impact of cardiovascular toxicity on patient outcomes is presented. Key aspects of this workflow include regular monitoring of cardiovascular function, early detection and management of cancer therapy-related cardiovascular toxicities, and optimization of cardiovascular risk factor control. By highlighting the gaps in knowledge in some areas, this review aims to emphasize the critical role of cardio-oncology research in ensuring the holistic well-being of patients with breast cancer.

Clinical Applications and Advancements of Positron Emission Tomography/Computed Tomography in Cardio-Oncology: A Comprehensive Literature Review and Emerging Perspectives.

PURPOSE OF REVIEW: Recent advancements in molecular biology, biotechnology, chemistry/radiochemistry, artificial intelligence, and imaging techniques have significantly propelled the field of cardiovascular molecular imaging. This review aims to provide a comprehensive overview of the current state of cardiovascular positron emission tomography (PET) imaging and cardiac computed tomography (CT), exploring their roles in elucidating molecular and cellular processes, enabling early disease detection, and guiding novel therapeutic interventions for cardiovascular conditions. RECENT FINDINGS: Cardiovascular PET imaging strives to uncover molecular and cellular events preceding visible anatomical manifestations or physiological changes. Meanwhile, cardiac CT has evolved into a multifaceted modality, offering insights into both anatomy and function. Utilizing advanced CT technologies allows for a thorough evaluation, encompassing fractional flow reserve, perfusion imaging, pericoronary adipose tissue attenuation, atherosclerotic plaque characterization, cardiomyopathies, structural cardiac abnormalities, and congenital heart anomalies. The emergence of hybrid imaging, combining PET and CT, presents innovative prospects in cardiology. This approach enables the simultaneous assessment of cardiac perfusion and coronary anatomy in a singular scan, providing complementary insights relevant to potential coronary artery disease. Despite the substantial potential impact, operational familiarity with this hybrid tool remains limited, and its integration into routine clinical practice warrants further exploration. In summary, the review underscores the transformative impact of recent technological advancements on cardiovascular molecular imaging. The integration of PET and CT, along with their individual capabilities, holds promise for early disease detection and informed clinical decision-making. While acknowledging the potential of hybrid imaging, it emphasizes the need for increased operational familiarity and continued exploration to facilitate its seamless integration into routine clinical practice. The insights gained from this review contribute to the ongoing dialogue in the field, offering a foundation for future research and advancements in cardiovascular imaging.

Management of Cancer Therapy-Related Cardiac Dysfunction: A Case-Based Review.

With an ever-expanding repertoire of cancer therapies, cardiologists increasingly encounter patients with cancer therapy-related cardiac dysfunction. This can range from asymptomatic mild left ventricular dysfunction to severe symptomatic congestive heart failure. A multidisciplinary approach involving oncologists and cardiologists is needed in the management of these patients. This case-based review provides a practical guide for clinicians regarding the diagnosis and management of cancer therapy-related cardiac dysfunction associated with commonly used cancer treatments: anthracyclines, human epidermal receptor 2-targeted therapies, and immune checkpoint inhibitors.

Enhancing nurse competence in early recognition of cardiotoxicity.

BACKGROUND: Preliminary research reveals that many nurses feel inadequate and possess limited knowledge when it comes to managing cardiotoxicity, underscoring the necessity for educational programs to enhance nursing skills in this area. METHODS: The aim of the study was to assess the impact of an educational intervention on nurses perceived self-efficacy in recognizing patients exhibiting symptoms of cancer treatment-related cardiotoxicity. The study was set in a 16-bed cardiac critical care unit (CCU) within a 462-bed hospital. The sample group was comprised of registered nurses (RNs) working on or floating to the CCU. The study used a within-subjects design. Participants completed a pre-education survey, attended one of six 30-minute education interventions, and completed a post-education survey. The outcome variables were 7 self-confidence questions from the Nursing Self-Efficacy Scale for Managing Cancer Treatment-Related Cardiotoxicity (NSS-CTC) on a 5-point Likert scale and one yes or no self-efficacy question. Descriptive statistics and paired T-tests were applied to analyze pre- and post-education surveys. RESULTS: The pre-and post-education comparative analysis for each of the 7 NSS-CTC self-confidence questions was statistically significant with test statistics ranging from t = 3.43 to t = 8.69 and p-values ranging from 0.0021 to less than 0.0001. All 26 RNs answered "yes" in their ability to detect symptoms of cancer therapy-related cardiotoxicity after the education. CONCLUSIONS: The lack of education for cardiac nurses against the backdrop of increasing cardiotoxicity in cancer patients showcases the essential need for cardiac nurse early symptom recognition education.

AI-Enhanced ECG Applications in Cardiology: Comprehensive Insights from the Current Literature with a Focus on COVID-19 and Multiple Cardiovascular Conditions.

The application of artificial intelligence (AI) in electrocardiography is revolutionizing cardiology and providing essential insights into the consequences of the COVID-19 pandemic. This comprehensive review explores AI-enhanced ECG (AI-ECG) applications in risk prediction and diagnosis of heart diseases, with a dedicated chapter on COVID-19-related complications. Introductory concepts on AI and machine learning (ML) are explained to provide a foundational understanding for those seeking knowledge, supported by examples from the literature and current practices. We analyze AI and ML methods for arrhythmias, heart failure, pulmonary hypertension, mortality prediction, cardiomyopathy, mitral regurgitation, hypertension, pulmonary embolism, and myocardial infarction, comparing their effectiveness from both medical and AI perspectives. Special emphasis is placed on AI applications in COVID-19 and cardiology, including detailed comparisons of different methods, identifying the most suitable AI approaches for specific medical applications and analyzing their strengths, weaknesses, accuracy, clinical relevance, and key findings. Additionally, we explore AI's role in the emerging field of cardio-oncology, particularly in managing chemotherapy-induced cardiotoxicity and detecting cardiac masses. This comprehensive review serves as both an insightful guide and a call to action for further research and collaboration in the integration of AI in cardiology, aiming to enhance precision medicine and optimize clinical decision-making.

How to utilize current guidelines to manage patients with cancer at high risk for heart failure.

Heart failure (HF) in patients with cancer is associated with high morbidity and mortality. The success of cancer therapy has resulted in an exponential rise in the population of cancer survivors, however cardiovascular disease (CVD) is now a major life limiting condition more than 5 years after cancer diagnosis [Sturgeon, Deng, Bluethmann, et al 40(48):3889-3897, 2019]. Prevention and early detection of CVD, including cardiomyopathy (CM) and HF is of paramount importance. The European Society of Cardiology (ESC) published guidelines on Cardio-Oncology (CO) [Lyon, López-Fernández, Couch, et al 43(41):4229-4361, 2022] detailing cardiovascular (CV) risk stratification, prevention, monitoring, diagnosis, and treatment throughout the course and following completion of cancer therapy. Here we utilize a case to summarize aspects of the ESC guideline relevant to HF clinicians, with a focus on risk stratification, early detection, prevention of CM and HF, and the role for guideline directed medical therapy in patients with cancer.

Time Relationship between the Occurrence of a Thromboembolic Event and the Diagnosis of Hematological Malignancies.

OBJECTIVES: Venous and arterial thromboembolism (VTE/ATE) often coexist with onco-hematologic diagnosis. This study aimed to assess the time relationship between the diagnosis of VTE/ATE and blood cancers. The second aim was to identify VTE/ATE risk factors related to the type of hematology disease and cardiac history. METHODS: A total of 1283 patients underwent cardio-oncology evaluation at the Institute of Hematology and Transfusion Medicine in Warsaw from March 2021 through March 2023 (2 years), and 101 (7.8%) cases were identified with VTE/ATE. RESULTS: ATE compared with VTE significantly occurred more often before the diagnosis and treatment of hematologic malignancy: 33/47 (70.2%) vs. 15/54 (27.8%), p < 0.0001. The risk of a VTE episode is exceptionally high in the first months after the diagnosis of an onco-hematological disease and the initiation of anticancer treatment. The higher frequency of VTE was associated with acute myeloid leukemia (17 cases/270 patients/6.30%/p = 0.055), acute lymphocytic leukemia (7 cases/76 patients/9.21%/p = 0.025), and chronic myeloproliferative disease (7 cases/48 patients/14.58%/p = 0.0003). Only the risk of VTE was significantly increased before (OR = 6.79; 95% CI: 1.85-24.95; p = 0.004) and after diagnosis of myeloproliferative disease (OR = 3.12; 95% CI: 1.06-9.16; p = 0.04). CONCLUSIONS: ATEs occur more often than VTE before a diagnosis of blood cancer. The risk of VTE is exceptionally high before and after diagnosis of chronic myeloproliferative disease.

Cancer Development and Progression in Patients with Heart Failure.

PURPOSE OF REVIEW: The co-occurrence of heart failure (HF) and cancer represents a complex and multifaceted medical challenge. Patients with prevalent cardiovascular disease (CVD), particularly HF, exhibit an increased risk of cancer development, raising questions about the intricate interplay between these two prevalent conditions. This review aims to explore the evolving landscape of cancer development in patients with HF, shedding light on potential mechanisms, risk factors, and clinical implications. RECENT FINDINGS: Epidemiological data suggests higher cancer incidences and higher cancer mortality in HF patients, which are potentially more common in patients with HF with preserved ejection fraction due to related comorbidities. Moreover, recent preclinical data identified novel pathways and mediators including the protein SerpinA3 as potential drivers of cancer progression in HF patients, suggesting HF as an individual risk factor for cancer development. The review emphasizes preliminary evidence supporting cancer development in patients with HF, which offers several important clinical interventions such as cancer screening in HF patients, prevention addressing both HF and cancer, and molecular targets to treat cancer. However, there is need for more detailed understanding of molecular and cellular cross-talk between cancer and HF which can be derived from prospective assessments of cancer-related outcomes in CV trials and preclinical research of molecular mechanisms.

Identifying mitigating strategies for endothelial cell dysfunction and hypertension in response to VEGF receptor inhibitors.

Vascular endothelial growth factor receptor inhibitors (VEGFRis) improve cancer survival but are associated with treatment-limiting hypertension, often attributed to endothelial cell (EC) dysfunction. Using phosphoproteomic profiling of VEGFRi-treated ECs, drugs were screened for mitigators of VEGFRi-induced EC dysfunction and validated in primary aortic ECs, mice, and canine cancer patients. VEGFRi treatment significantly raised systolic blood pressure (SBP) and increased markers of endothelial and renal dysfunction in mice and canine cancer patients. α-Adrenergic-antagonists were identified as drugs that most oppose the VEGFRi proteomic signature. Doxazosin, one such α-antagonist, prevented EC dysfunction in murine, canine, and human aortic ECs. In mice with sorafenib-induced-hypertension, doxazosin mitigated EC dysfunction but not hypertension or glomerular endotheliosis, while lisinopril mitigated hypertension and glomerular endotheliosis without impacting EC function. Hence, reversing EC dysfunction was insufficient to mitigate VEGFRi-induced-hypertension in this mouse model. Canine cancer patients with VEGFRi-induced-hypertension were randomized to doxazosin or lisinopril and both agents significantly decreased SBP. The canine clinical trial supports safety and efficacy of doxazosin and lisinopril as antihypertensives for VEGFRi-induced-hypertension and the potential of trials in canines with spontaneous cancer to accelerate translation. The overall findings demonstrate the utility of phosphoproteomics to identify EC-protective agents to mitigate cardio-oncology side effects.

Cardio-oncology: chances and challenges.

Cardio-oncology is an emerging field that aims to ensure optimal cancer treatment while minimising cardiovascular toxicity. The management of cardiovascular toxicity is critical because it can lead to premature discontinuation of treatment, increasing the risk of cancer recurrence and mortality. The 2022 European Society of Cardiology guidelines were a milestone in advocating a patient-centred, multidisciplinary approach. Key components include risk stratification and a standardised criterion for adverse events, incorporating definitions from the International Cardio-Oncology Society. Effective risk stratification, supported by imaging and biomarkers, helps to anticipate cardiovascular problems and implement preventive measures. Future research should focus on understanding mechanisms, developing preventive strategies and implementing personalised medicine. Education and reducing disparities in care are essential to advance cardio-oncology and improve patient outcomes.

Racial disparities in TAVR outcomes in patients with cancer.

Background: Advances in cancer therapies and improvement in survival of cancer patients have led to a growing number of patients with both cancer and severe aortic stenosis (AS). Transcatheter aortic valve replacement (TAVR) has been shown to be a safe and effective treatment option for this patient population. There are established racial disparities in utilization and outcomes of both cancer treatments and TAVR. However, the effect of race on TAVR outcomes in cancer patients has not been studied. Objectives: The purpose of this study was to investigate racial disparities in outcomes of TAVR in cancer patients. Methods: 343 patients with cancer who underwent TAVR at a single center over a 6-year period were included in the study. The primary endpoint was a composite of 1-year mortality, stroke, and bleeding. Secondary outcomes included individual components of the primary endpoint as well as 30-day mortality, structural complications, vascular access complications, and conduction system complications. Outcomes were compared between black and white patients by comparing incidence rates. Results: Baseline characteristics including age, sex, BMI, medical comorbidities, STS score, and echocardiographic parameters were similar between races, aside from significantly higher rates of CKD (50.0% vs. 26.6%, p = 0.005) and ESRD (18.4% vs. 4.9%, p = 0.005) in black compared to white cancer patients. There was a trend toward worse outcomes in black cancer patients with regard to a composite endpoint of 1-year mortality, stroke, and major bleeding (35.7% vs. 22.6%, p = 0.095), primarily driven by higher 1-year mortality (31.0% vs. 17.6%, p = 0.065). 30-day mortality was twice as high in black cancer patients than in white cancer patients (4.8% vs. 2.3%, p = 0.018). Conclusions: There is a trend toward worse TAVR outcomes in black cancer patients, with higher periprocedural complication rates and mortality, compared to white cancer patients. Further studies are needed to elucidate the structural, socioeconomic, and biological factors that contribute to racial differences in outcomes.

Autoantibody profiling of patients with immune checkpoint inhibitor-associated myocarditis: a pilot study.

Background: Immune checkpoint inhibitor (ICI)-associated myocarditis is a rare, but potentially fatal, immune-related adverse event. Hence, identifying biomarkers is critical for selecting and managing patients receiving ICI treatment. Serum autoantibodies (AAbs) in patients with ICI myocarditis may serve as potential biomarkers for predicting, diagnosing, and prognosing ICI myocarditis. We conducted a pilot study using a human proteome microarray with approximately 17,000 unique full-length human proteins to investigate AAbs associated with ICI myocarditis. Methods and results: AAb profiling was performed using sera collected from three patients with ICI myocarditis before the start of ICI treatment and immediately after myocarditis onset. All patients received anti-programmed death-1 antibody monotherapy. At baseline, 116, 296, and 154 autoantigens reacted positively to immunoglobulin G (IgG) in the serum samples from Cases 1, 2, and 3, respectively. Among these proteins, the recombination signal-binding protein for the immunoglobulin kappa J region (RBPJ) was recognized by all three samples, and 32 autoantigens were recognized by any two of the three samples. At the onset of ICI myocarditis, compared to baseline, 48, 114, and 5 autoantigens reacted more strongly with IgG in the serum samples from Cases 1, 2, and 3, respectively. Among these, antibodies against eukaryotic translation initiation factor 4E binding protein 3 (EIF4EBP3) were the most upregulated, with a 38-fold increase. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighted that B-cell receptor signaling, leukocyte transendothelial migration, and thymus development were among the most affected pathways. Enrichment analyses using DisGeNET revealed that proteins reacting to AAbs detected in patients with ICI myocarditis are associated with several diseases, including dilated cardiomyopathy and muscle weakness. Conclusions: This pilot study provides the first integrated analysis of serum AAb profiling in patients with ICI myocarditis and identifies novel candidate markers associated with an increased risk of developing ICI myocarditis and its pathogenesis. However, our results require further independent validation in clinical trials involving a larger number of patients.

Blood Pressure and Cardiovascular Risk in Women With Breast Cancer: The Pathways Heart Study.

Background: Hypertension is an important contributor to cardiovascular disease (CVD) in breast cancer (BC) survivors; however, research on blood pressure (BP) and CVD outcomes in BC survivors is limited. Objectives: The purpose of this study was to better characterize the association between BP and CVD in a large, longitudinal cohort of BC patients. Methods: Women with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California were matched 1:5 to women without BC. Patient data were obtained from electronic health records. Multivariable Cox regression and penalized spline models were used to explore the linear and nonlinear relationship of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on CVD outcomes. Results: BC cases (n = 12,713) and controls (n = 55,886) had median follow-up of 9.6 years (IQR: 5.0-11.9 years). Women with BC had a mean age of 60.6 years; 64.8% were non-Hispanic White. For ischemic heart disease (IHD), every 10 mmHg increase in SBP and DBP was associated with 1.23 (95% CI: 1.14-1.33) and 1.10 (95% CI: 0.98-1.24) risk, respectively, in women with BC. For stroke, every 10 mmHg increase in SBP and DBP was associated with a 1.45 (95% CI: 1.34-1.58) and 1.91 (95% CI: 1.68-2.18) risk, respectively. A U-shaped relationship was observed between heart failure/cardiomyopathy and BP. The associations between BP and risk of IHD, stroke, and any primary CVD were not statistically different comparing women with BC to controls, but risks varied by BC status for heart failure/cardiomyopathy (P for interaction = 0.01). Conclusions: Women with and without BC showed similar risks for IHD, stroke, and any primary CVD suggesting similar BP targets should be pursued regardless of BC survivorship status.

Cardioprotection strategies for anthracycline cardiotoxicity.

Thanks to the fantastic progress in cancer therapy options, there is a growing population of cancer survivors. This success has resulted in a need to focus much effort into improving the quality of life of this population. Cancer and cardiovascular disease share many common risk factors and have an interplay between them, with one condition mechanistically affecting the other and vice versa. Furthermore, widely prescribed cancer therapies have known toxic effects in the cardiovascular system. Anthracyclines are the paradigm of efficacious cancer therapy widely prescribed with a strong cardiotoxic potential. While some cancer therapies cardiovascular toxicities are transient, others are irreversible. There is a growing need to develop cardioprotective therapies that, when used in conjunction with cancer therapies, can prevent cardiovascular toxicity and thus improve long-term quality of life in survivors. The field has three main challenges: (i) identification of the ultimate mechanisms leading to cardiotoxicity to (ii) identify specific therapeutic targets, and (iii) more sensible diagnostic tools to early identify these conditions. In this review we will focus on the cardioprotective strategies tested and under investigation. We will focus this article into anthracycline cardiotoxicity since it is still the agent most widely prescribed, the one with higher toxic effects on the heart, and the most widely studied.