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.

Digital Technologies in Cardiac Rehabilitation: A Science Advisory From the American Heart Association.

Cardiac rehabilitation has strong evidence of benefit across many cardiovascular conditions but is underused. Even for those patients who participate in cardiac rehabilitation, there is the potential to better support them in improving behaviors known to promote optimal cardiovascular health and in sustaining those behaviors over time. Digital technology has the potential to address many of the challenges of traditional center-based cardiac rehabilitation and to augment care delivery. This American Heart Association science advisory was assembled to guide the development and implementation of digital cardiac rehabilitation interventions that can be translated effectively into clinical care, improve health outcomes, and promote health equity. This advisory thus describes the individual digital components that can be delivered in isolation or as part of a larger cardiac rehabilitation telehealth program and highlights challenges and future directions for digital technology generally and when used in cardiac rehabilitation specifically. It is also intended to provide guidance to researchers reporting digital interventions and clinicians implementing these interventions in practice and to advance a framework for equity-centered digital health in cardiac rehabilitation.

Cardiovascular Imaging in Contemporary Cardio-Oncology: A Scientific Statement From the American Heart Association.

Advances in cancer therapeutics have led to dramatic improvements in survival, now inclusive of nearly 20 million patients and rising. However, cardiovascular toxicities associated with specific cancer therapeutics adversely affect the outcomes of patients with cancer. Advances in cardiovascular imaging have solidified the critical role for robust methods for detecting, monitoring, and prognosticating cardiac risk among patients with cancer. However, decentralized evaluations have led to a lack of consensus on the optimal uses of imaging in contemporary cancer treatment (eg, immunotherapy, targeted, or biological therapy) settings. Similarly, available isolated preclinical and clinical studies have provided incomplete insights into the effectiveness of multiple modalities for cardiovascular imaging in cancer care. The aims of this scientific statement are to define the current state of evidence for cardiovascular imaging in the cancer treatment and survivorship settings and to propose novel methodological approaches to inform the optimal application of cardiovascular imaging in future clinical trials and registries. We also propose an evidence-based integrated approach to the use of cardiovascular imaging in routine clinical settings. This scientific statement summarizes and clarifies available evidence while providing guidance on the optimal uses of multimodality cardiovascular imaging in the era of emerging anticancer therapies.

Breast cancer incidence and mortality by metabolic syndrome and obesity: The Women's Health Initiative.

BACKGROUND: In the Women's Health Initiative (WHI) randomized trial, dietary intervention significantly reduced breast cancer mortality, especially in women with more metabolic syndrome (MetS) components. Therefore, this study investigated the associations of MetS and obesity with postmenopausal breast cancer after long-term follow-up in the WHI clinical trials. METHODS: A total of 68,132 postmenopausal women, without prior breast cancer and with normal mammogram, were entered into WHI randomized clinical trials; 63,330 women with an entry MetS score comprised the study population. At entry, body mass index (BMI) was determined; MetS score (0, 1-2, and 3-4) included the following: (1) high waist circumference (≥88 cm), (2) high blood pressure (systolic ≥130 mm Hg and/or diastolic ≥85 mm Hg, or hypertension history), (3) high-cholesterol history, and (4) diabetes history. Study outcomes included breast cancer incidence, breast cancer mortality, deaths after breast cancer, and results by hormone receptor status. RESULTS: After a >20-year mortality follow-up, a higher MetS score (3-4), adjusted for BMI, was significantly associated with more poor prognosis, estrogen receptor (ER)-positive, progesterone receptor (PR)-negative cancers (p = .03), 53% more deaths after breast cancer (p < .001), and 44% higher breast cancer mortality (p = .03). Obesity status, adjusted for MetS score, was significantly associated with more good prognosis, ER-positive, PR-positive cancers (p < .001), more total breast cancers (p < .001), and more deaths after breast cancer (p < .001), with higher breast cancer mortality only in women with severe obesity (BMI, ≥35 kg/m2; p < .001). CONCLUSIONS: MetS and obesity status have independent, but differential, adverse associations with breast cancer receptor subtypes and breast cancer mortality risk. Both represent separate targets for breast cancer prediction and prevention strategies.

Association of clonal hematopoiesis and mosaic chromosomal alterations with solid malignancy incidence and mortality.

BACKGROUND: Understanding the impact of clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) on solid tumor risk and mortality can shed light on novel cancer pathways. METHODS: The authors analyzed whole genome sequencing data from the Trans-Omics for Precision Medicine Women's Health Initiative study (n = 10,866). They investigated the presence of CHIP and mCA and their association with the development and mortality of breast, lung, and colorectal cancers. RESULTS: CHIP was associated with higher risk of breast (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.03-1.64; p = .02) but not colorectal (p = .77) or lung cancer (p = .32). CHIP carriers who developed colorectal cancer also had a greater risk for advanced-stage (p = .01), but this was not seen in breast or lung cancer. CHIP was associated with increased colorectal cancer mortality both with (HR, 3.99; 95% CI, 2.41-6.62; p < .001) and without adjustment (HR, 2.50; 95% CI, 1.32-4.72; p = .004) for advanced-stage and a borderline higher breast cancer mortality (HR, 1.53; 95% CI, 0.98-2.41; p = .06). Conversely, mCA (cell fraction [CF] >3%) did not correlate with cancer risk. With higher CFs (mCA >5%), autosomal mCA was associated with increased breast cancer risk (HR, 1.39; 95% CI, 1.06-1.83; p = .01). There was no association of mCA (>3%) with breast, colorectal, or lung mortality except higher colon cancer mortality (HR, 2.19; 95% CI, 1.11-4.3; p = .02) with mCA >5%. CONCLUSIONS: CHIP and mCA (CF >5%) were associated with higher breast cancer risk and colorectal cancer mortality individually. These data could inform on novel pathways that impact cancer risk and lead to better risk stratification.

Vascular Impact of Cancer Therapies: The Case of BTK (Bruton Tyrosine Kinase) Inhibitors.

Novel targeted cancer therapies have revolutionized oncology therapies, but these treatments can have cardiovascular complications, which include heterogeneous cardiac, metabolic, and vascular sequelae. Vascular side effects have emerged as important considerations in both cancer patients undergoing active treatment and cancer survivors. Here, we provide an overview of vascular effects of cancer therapies, focusing on small-molecule kinase inhibitors and specifically inhibitors of BTK (Bruton tyrosine kinase), which have revolutionized treatment and prognosis for B-cell malignancies. Cardiovascular side effects of BTK inhibitors include atrial fibrillation, increased risk of bleeding, and hypertension, with the former 2 especially providing a treatment challenge for the clinician. Cardiovascular complications of small-molecule kinase inhibitors can occur through either on-target (targeting intended target kinase) or off-target kinase inhibition. We will review these concepts and focus on the case of BTK inhibitors, highlight the emerging data suggesting an off-target effect that may provide insights into development of arrhythmias, specifically atrial fibrillation. We believe that cardiac and vascular sequelae of novel targeted cancer therapies can provide insights into human cardiovascular biology.

Association of atrial fibrillation and outcomes in patients undergoing bone marrow transplantation.

AIMS: Haematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for several malignant and non-malignant haematologic conditions. Patients undergoing HSCT are at an increased risk of developing atrial fibrillation (AF). We hypothesized that a diagnosis of AF would be associated with poor outcomes in patients undergoing HSCT. METHODS AND RESULTS: The National Inpatient Sample (2016-19) was queried with ICD-10 codes to identify patients aged >50 years undergoing HSCT. Clinical outcomes were compared between patients with and without AF. A multivariable regression model adjusting for demographics and comorbidities was used to calculate the adjusted odds ratio (aOR) and regression coefficients with corresponding 95% confidence intervals and P-values. A total of 50 570 weighted hospitalizations for HSCT were identified, out of which 5820 (11.5%) had AF. Atrial fibrillation was found to be independently associated with higher inpatient mortality (aOR 2.75; 1.9-3.98; P < 0.001), cardiac arrest (aOR 2.86; 1.55-5.26; P = 0.001), acute kidney injury (aOR 1.89; 1.6-2.23; P < 0.001), acute heart failure exacerbation (aOR 5.01; 3.54-7.1; P < 0.001), cardiogenic shock (aOR 7.73; 3.17-18.8; P < 0.001), and acute respiratory failure (aOR 3.24; 2.56-4.1; P < 0.001) as well as higher mean length of stay (LOS) (+2.67; 1.79-3.55; P < 0.001) and cost of care (+67 529; 36 630-98 427; P < 0.001). CONCLUSION: Among patients undergoing HSCT, AF was independently associated with poor in-hospital outcomes, higher LOS, and cost of care.

Defining cardiovascular toxicities of cancer therapies: an International Cardio-Oncology Society (IC-OS) consensus statement.

The discipline of Cardio-Oncology has seen tremendous growth over the past decade. It is devoted to the cardiovascular (CV) care of the cancer patient, especially to the mitigation and management of CV complications or toxicities of cancer therapies, which can have profound implications on prognosis. To that effect, many studies have assessed CV toxicities in patients undergoing various types of cancer therapies; however, direct comparisons have proven difficult due to lack of uniformity in CV toxicity endpoints. Similarly, in clinical practice, there can be substantial differences in the understanding of what constitutes CV toxicity, which can lead to significant variation in patient management and outcomes. This document addresses these issues and provides consensus definitions for the most commonly reported CV toxicities, including cardiomyopathy/heart failure and myocarditis, vascular toxicity, and hypertension, as well as arrhythmias and QTc prolongation. The current document reflects a harmonizing review of the current landscape in CV toxicities and the definitions used to define these. This consensus effort aims to provide a structure for definitions of CV toxicity in the clinic and for future research. It will be important to link the definitions outlined herein to outcomes in clinical practice and CV endpoints in clinical trials. It should facilitate communication across various disciplines to improve clinical outcomes for cancer patients with CV diseases.

Trends in heart disease mortality among breast cancer survivors in the US, 1975-2017.

PURPOSE: Heart disease is a significant concern among breast cancer survivors, in part due to cardiotoxic treatments including chemotherapy and radiotherapy. Long-term trends in heart disease mortality have not been well characterized. We examined heart disease mortality trends among US breast cancer survivors by treatment type. METHODS: We included first primary invasive breast cancer survivors diagnosed between 1975 and 2016 (aged 18-84; survived 12 + months; received initial chemotherapy, radiotherapy, or surgery) in the SEER-9 Database. Standardized mortality ratios (SMRs) and 10-year cumulative heart disease mortality estimates accounting for competing events were calculated by calendar year of diagnosis and initial treatment regimen. Ptrends were assessed using Poisson regression. All statistical tests were 2-sided. RESULTS: Of 516,916 breast cancer survivors, 40,812 died of heart disease through 2017. Heart disease SMRs declined overall from 1975-1979 to 2010-2016 (SMR 1.01 [95%CI: 0.98, 1.03] to 0.74 [0.69, 0.79], ptrend < 0.001). This decline was also observed for survivors treated with radiotherapy alone and chemotherapy plus radiotherapy. A sharper decline in heart disease SMRs was observed from 1975 to 1989 for left-sided radiotherapy, compared to right-sided. In contrast, there was a non-significant increasing trend in SMRs for chemotherapy alone, and significant by regional stage (ptrend = 0.036). Largest declines in 10-year cumulative mortality were observed from 1975-1984 to 2005-2016 among surgery only: 7.02% (95%CI: 6.80%, 7.23%) to 4.68% (95%CI: 4.39%, 4.99%) and radiotherapy alone: 6.35% (95%CI: 5.95%, 6.77%) to 2.94% (95%CI: 2.73%, 3.16%). CONCLUSIONS: We observed declining heart disease mortality trends by most treatment types yet increasing for regional stage patients treated with chemotherapy alone, highlighting a need for additional studies with detailed treatment data and cardiovascular management throughout cancer survivorship.

Multimodality imaging to distinguish between benign and malignant cardiac masses.

BACKGROUND: To compare the diagnostic accuracy of CMR and FDG-PET/CT and their complementary role to distinguish benign vs malignant cardiac masses. METHODS: Retrospectively assessed patients with cardiac mass who underwent CMR and FDG-PET/CT within a month between 2003 and 2018. RESULTS: 72 patients who had CMR and FDG-PET/CT were included. 25 patients (35%) were diagnosed with benign and 47 (65%) were diagnosed with malignant masses. 56 patients had histological correlation: 9 benign and 47 malignant masses. CMR and FDG-PET/CT had a high accuracy in differentiating benign vs malignant masses, with the presence of CMR features demonstrating a higher sensitivity (98%), while FDG uptake with SUVmax/blood pool ≥ 3.0 demonstrating a high specificity (88%). Combining multiple (> 4) CMR features and FDG uptake (SUVmax/blood pool ratio ≥ 3.0) yielded a sensitivity of 85% and specificity of 88% to diagnose malignant masses. Over a mean follow-up of 2.6 years (IQR 0.3-3.8 years), risk-adjusted mortality were highest among patients with an infiltrative border on CMR (adjusted HR 3.1; 95% CI 1.5-6.5; P = .002) or focal extracardiac FDG uptake (adjusted HR 3.8; 95% CI 1.9-7.7; P < .001). CONCLUSION: Although CMR and FDG-PET/CT can independently diagnose benign and malignant masses, the combination of these modalities provides complementary value in select cases.

Cardioprotection for Anti-HER2 Therapy: Considerations for Primary Prevention and Use in Mildly Reduced Left Ventricular Ejection Fraction.

PURPOSE OF REVIEW: This review summarizes current HER2-targeted therapies and clinical studies that have investigated primary and secondary prevention of cardiac dysfunction for HER2 + breast cancer patients undergoing targeted therapy. RECENT FINDINGS: Primary and secondary prevention clinical trials highlight the importance of cardioprotective measures during HER2 + cancer treatment. Together, these studies suggest the safety of neurohormonal drugs, the importance for an individualized approach in starting cardiopreventive therapies, and the potential to expand HER2 + treatment options to patients with cardiac dysfunction. Cardiac dysfunction is a concerning adverse effect for HER2-targeted treatment. The goal of primary and secondary prevention is to prevent (further) cardiac function decline and heart failure symptoms, while delivering appropriate cancer therapy. Clinical trials investigating preventative therapies in the context of primary and secondary prevention are paving the path for reducing adverse cardiac effects and expanding treatment options for patients previously unable to undergo HER + therapy.

Longitudinal profiling of clonal hematopoiesis provides insight into clonal dynamics.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP), the age-related expansion of mutant hematopoietic stem cells, confers risk for multiple diseases of aging including hematologic cancer and cardiovascular disease. Whole-exome or genome sequencing can detect CHIP, but due to those assays' high cost, most population studies have been cross-sectional, sequencing only a single timepoint per individual. RESULTS: We developed and validated a cost-effective single molecule molecular inversion probe sequencing (smMIPS) assay for detecting CHIP, targeting the 11 most frequently mutated genes in CHIP along with 4 recurrent mutational hotspots. We sequenced 548 multi-timepoint samples collected from 182 participants in the Women's Health Initiative cohort, across a median span of 16 years. We detected 178 driver mutations reaching variant allele frequency ≥ 2% in at least one timepoint, many of which were detectable well below this threshold at earlier timepoints. The majority of clonal mutations (52.1%) expanded over time (with a median doubling period of 7.43 years), with the others remaining static or decreasing in size in the absence of any cytotoxic therapy. CONCLUSIONS: Targeted smMIPS sequencing can sensitively measure clonal dynamics in CHIP. Mutations that reached the conventional threshold for CHIP (2% frequency) tended to continue growing, indicating that after CHIP is acquired, it is generally not lost. The ability to cost-effectively profile CHIP longitudinally will enable future studies to investigate why some CHIP clones expand, and how their dynamics relate to health outcomes at a biobank scale.

Cardio-oncology: Implications for Clinical Practice for Women.

PURPOSE OF REVIEW: Clinical cardio-oncology considerations specific to women span across many areas and are particularly relevant for management of patients with sex-specific cancers, such as breast cancer. RECENT FINDINGS: Major improvement in breast cancer survivorship over the last decade and the recognition of CV disease as the second leading cause of death among survivors point to the relevance of long-term cardiovascular (CV) safety. This review summarizes the CV effects associated with multimodality breast cancer treatments and contemporary approach to CV risk stratification, prevention, early detection, monitoring, and management at the time of cancer diagnosis, during and after completion of treatment. We highlight the growing role of a multidisciplinary, team-based approach for comprehensive CV and oncology care through the entire cancer treatment continuum, from diagnosis through survivorship.

Percutaneous coronary intervention in patients with cancer and readmissions within 90 days for acute myocardial infarction and bleeding in the USA.

AIMS: The post-discharge outcomes of patients with cancer who undergo PCI are not well understood. This study evaluates the rates of readmissions within 90 days for acute myocardial infarction (AMI) and bleeding among patients with cancer who undergo percutaneous coronary intervention (PCI). METHODS AND RESULTS: Patients treated with PCI in the years from 2010 to 2014 in the US Nationwide Readmission Database were evaluated for the influence of cancer on 90-day readmissions for AMI and bleeding. A total of 1 933 324 patients were included in the analysis (2.7% active cancer, 6.8% previous history of cancer). The 90-day readmission for AMI after PCI was higher in patients with active cancer (12.1% in lung, 10.8% in colon, 7.5% in breast, 7.0% in prostate, and 9.1% for all cancers) compared to 5.6% among patients with no cancer. The 90-day readmission for bleeding after PCI was higher in patients with active cancer (4.2% in colon, 1.5% in lung, 1.4% in prostate, 0.6% in breast, and 1.6% in all cancer) compared to 0.6% among patients with no cancer. The average time to AMI readmission ranged from 26.7 days for lung cancer to 30.5 days in colon cancer, while the average time to bleeding readmission had a higher range from 38.2 days in colon cancer to 42.7 days in breast cancer. CONCLUSIONS: Following PCI, patients with cancer have increased risk for readmissions for AMI or bleeding, with the magnitude of risk depending on both cancer type and the presence of metastasis.

Cardiometabolic risk factors and survival after cancer in the Women's Health Initiative.

BACKGROUND: Cardiometabolic abnormalities are a leading cause of death among women, including women with cancer. METHODS: This study examined the association between prediagnosis cardiovascular health and total and cause-specific mortality among 12,076 postmenopausal women who developed local- or regional-stage invasive cancer in the Women's Health Initiative (WHI). Cardiovascular risk factors included waist circumference, hypertension, high cholesterol, and type 2 diabetes. Obesity-related cancers included breast cancer, colorectal cancer, endometrial cancer, kidney cancer, pancreatic cancer, ovarian cancer, stomach cancer, liver cancer, and non-Hodgkin lymphoma. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for important predictors of survival. RESULTS: After a median follow-up of 10.0 years from the date of the cancer diagnosis, there were 3607 total deaths, with 1546 (43%) due to cancer. Most participants (62.9%) had 1 or 2 cardiometabolic risk factors, and 8.1% had 3 or 4. In adjusted models, women with 3 to 4 risk factors (vs none) had a higher risk of all-cause mortality (HR, 1.99; 95% CI, 1.73-2.30), death due to cardiovascular disease (CVD) (HR, 4.01; 95% CI, 2.88-5.57), cancer-specific mortality (HR, 1.37; 95% CI, 1.1-1.72), and other-cause mortality (HR, 2.14; 95% CI, 1.70-2.69). A higher waist circumference was associated with greater all-cause mortality (HR, 1.17; 95% CI, 1.06-1.30) and cancer-specific mortality (HR, 1.22; 95% CI, 1.04-1.42). CONCLUSIONS: Among postmenopausal women diagnosed with cancer in the WHI, cardiometabolic risk factors before the cancer diagnosis were associated with greater all-cause, CVD, cancer-specific, and other-cause mortality. These results raise hypotheses regarding potential clinical intervention strategies targeting cardiometabolic abnormalities that require future prospective studies for confirmation. LAY SUMMARY: This study uses information from the Women's Health Initiative (WHI) to find out whether cardiac risk factors are related to a greater risk of dying among older women with cancer. The WHI is the largest study of medical problems faced by older women in this country. The results show that women who have 3 or 4 risk factors are more likely to die of any cause, heart disease, or cancer in comparison with women with no risk factors. It is concluded that interventions to help to lower the burden of cardiac risk factors can have an important impact on survivorship among women with cancer.

Long-term follow-up assessment of cardiac safety in SAFE-HEaRt, a clinical trial evaluating the use of HER2-targeted therapies in patients with breast cancer and compromised heart function.

PURPOSE: HER2-targeted therapies are associated with cardiotoxicity which is usually asymptomatic and reversible. We report the updated cardiac safety assessment of patients with compromised heart function receiving HER2-targeted therapy for breast cancer, enrolled in the SAFE-HEaRt trial, at a median follow-up of 3.5 years. METHODS: Thirty patients with stage I-IV HER2-positive breast cancer receiving trastuzumab with or without pertuzumab, or ado-trastuzumab emtansine (T-DM1), with asymptomatic LVEF (left ventricular ejection fraction) 40-49%, were started on cardioprotective medications, with the primary endpoint being completion of HER2-targeted therapy without cardiac events (CE) or protocol-defined asymptomatic worsening of LVEF. IRB-approved follow-up assessment included 23 patients. RESULTS: Median follow-up as of June 2020 is 42 months. The study met its primary endpoint with 27 patients (90%) completing their HER2-targeted therapies without cardiac issues. Of the 23 evaluable patients at long-term f/u, 14 had early stage breast cancer, and 9 had metastatic disease, 8 of whom remained on HER2-targeted therapies. One patient developed symptomatic heart failure with no change in LVEF. There were no cardiac deaths. The mean LVEF improved to 52.1% from 44.9% at study baseline, including patients who remained on HER2-targeted therapy, and those who received prior anthracyclines. CONCLUSIONS: Long-term follow-up of the SAFE-HEaRt study continues to provide safety data of HER2-targeted therapy use in patients with compromised heart function. The late development of cardiac dysfunction is uncommon and continued multi-disciplinary oncologic and cardiac care of patients is vital for improved patient outcomes.

Right ventricular free wall strain in acutely decompensated heart failure patients with ischemic and non-ischemic cardiomyopathy.

AIMS: Right ventricular (RV) dysfunction is a predictor of adverse outcomes among patients with HF with reduced ejection fraction (HFrEF); however, differences in RV parameters in HFrEF patients with ischemic (ICM) and non-ischemic cardiomyopathies (NICM) are not well understood. We investigated echocardiographic characteristics, including RV strain, in patients with acute decompensated heart failure (ADHF) and compared patients with ICM and NICM etiology. METHODS: Consecutive patients who presented with ADHF and NYHA class III-IV were prospectively enrolled if they had LVEF < 40% and history of ICM or NICM. All patients underwent clinical exam, laboratory evaluation and 2-D echocardiographic assessment of the left ventricular (LV) and RV function, LV and RV global longitudinal strain (LVGLS, RVGLS), and RV free wall strain (RVfwLS). RESULTS: Of 84 patients, 44 had ICM and 40 NICM. The groups had similar blood pressure, NT-proBNP, and echocardiographic parameters of LV function including LVGLS. Absolute RVGLS values were lower than RVfwLS values in both groups. Patients with NICM had significantly lower RVfwLS, but not RVGLS, compared to patients with ICM (-13% to -17%, p = 0.006). Similar differences in RVfwLS were seen in patients in NYHA class III (NICM vs ICM: -13% and -17%, respectively, 95% CI: -8.5 to -.5) and NYHA class IV (NICM vs ICM: -13.8% and -17%, respectively, 95% CI: -6.4 to -.59). CONCLUSION: Among patients hospitalized with ADHF, patients with nonischemic etiology compared with the patients with ICM, have more severe RV dysfunction measured by RVfwLS, despite similar extent of LV impairment and the same functional limitation class.

Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis.

AIMS: Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented. METHODS AND RESULTS: From an international registry of patients with ICI-associated myocarditis, clinical, CMR, and histopathological findings were collected. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. In 103 patients diagnosed with ICI-associated myocarditis who had a CMR, the mean left ventricular ejection fraction (LVEF) was 50%, and 61% of patients had an LVEF ≥50%. Late gadolinium enhancement (LGE) was present in 48% overall, 55% of the reduced EF, and 43% of the preserved EF cohort. Elevated T2-weighted short tau inversion recovery (STIR) was present in 28% overall, 30% of the reduced EF, and 26% of the preserved EF cohort. The presence of LGE increased from 21.6%, when CMR was performed within 4 days of admission to 72.0% when CMR was performed on Day 4 of admission or later. Fifty-six patients had cardiac pathology. Late gadolinium enhancement was present in 35% of patients with pathological fibrosis and elevated T2-weighted STIR signal was present in 26% with a lymphocytic infiltration. Forty-one patients (40%) had MACE over a follow-up time of 5 months. The presence of LGE, LGE pattern, or elevated T2-weighted STIR were not associated with MACE. CONCLUSION: These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis.

Management of Cardiovascular Disease in Women With Breast Cancer.

Cardio-oncology is a rapidly developing field which seeks to improve patient outcomes through enhanced clinical and research collaboration across the disciplines of oncology and cardiology. Breast cancer (BC) is the most common cancer diagnosis among women in the United States and, as decades of research have resulted in decreased mortality rates, there has been an increasing focus on reducing short- and long-term treatment toxicity and improving morbidity among survivors. Preexisting or emergent cardiovascular disease in a patient with BC requires a multidisciplinary, team-based approach to balance the need for curative cancer treatment while preventing increased cardiovascular disease morbidity and mortality. Given the overlap in risk factors for BC and cardiovascular disease, such as smoking, sedentary lifestyle, and obesity, there are opportunities for cardiovascular disease prevention and detection before, during, and after BC treatment. Cardiology providers also play an important role in preventing, diagnosing, and treating cardiac dysfunction and other cardiovascular complications that may develop as a result of BC treatment. A number of recent clinical practice guidelines address approaches to cardiotoxicity, however, they focus on specific agents or treatment modality, rather than on collaborative disease management. In this review we present cardiovascular concerns associated with contemporary, multimodality BC treatment and illustrate how current guideline recommendations apply to clinical cardiology and oncology questions. We provide a cardio-oncology team-based approach to cardiovascular assessment and management of patients with BC from diagnosis through treatment and in survivorship.

Cardio-Oncology: Vascular and Metabolic Perspectives: A Scientific Statement From the American Heart Association.

Cardio-oncology has organically developed as a new discipline within cardiovascular medicine as a result of the cardiac and vascular adverse sequelae of the major advances in cancer treatment. Patients with cancer and cancer survivors are at increased risk of vascular disease for a number of reasons. First, many new cancer therapies, including several targeted therapies, are associated with vascular and metabolic complications. Second, cancer itself serves as a risk factor for vascular disease, especially by increasing the risk for thromboembolic events. Finally, recent data suggest that common modifiable and genetic risk factors predispose to both malignancies and cardiovascular disease. Vascular complications in patients with cancer represent a new challenge for the clinician and a new frontier for research and investigation. Indeed, vascular sequelae of novel targeted therapies may provide insights into vascular signaling in humans. Clinically, emerging challenges are best addressed by a multidisciplinary approach in which cardiovascular medicine specialists and vascular biologists work closely with oncologists in the care of patients with cancer and cancer survivors. This novel approach realizes the goal of providing superior care through the creation of cardio-oncology consultative services and the training of a new generation of cardiovascular specialists with a broad understanding of cancer treatments.