Search

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.

Cardioprotective therapies represent an important avenue to reduce treatment-limiting cardiotoxicities in patients receiving chemotherapy. However, the optimal duration, strategy and long-term efficacy of empiric cardio-protection remains unknown.Leveraging the MEDLINE/Pubmed, CENTRAL and clinicaltrials.gov databases, we identified all randomised controlled trials investigating cardioprotective therapies from inception to November 2021 (PROSPERO-ID:CRD42021265006). Cardioprotective classes included ACEIs, ARBs, Beta-blockers, dexrazoxane (DEX), statins and mineralocorticoid receptor antagonists. The primary end-point was new-onset heart failure (HF). Secondary outcomes were the mean difference in left ventricular ejection fraction (LVEF) change, hypotension and all-cause mortality. Network meta-analyses were used to assess the cardioprotective effects of each therapy to deduce the most effective therapies. Both analyses were performed using a Bayesian random effects model to estimate risk ratios (RR) and 95% credible intervals (95% CrI).Overall, from 726 articles, 39 trials evaluating 5931 participants (38.0 ± 19.1 years, 72.0% females) were identified. The use of any cardioprotective strategy associated with reduction in new-onset HF (RR:0.32; 95% CrI:0.19-0.55), improved LVEF (mean difference: 3.92%; 95% CrI:2.81-5.07), increased hypotension (RR:3.27; 95% CrI:1.38-9.87) and no difference in mortality. Based on control arms, the number-needed-to-treat for 'any' cardioprotective therapy to prevent one incident HF event was 45, including a number-needed-to-treat of 21 with ≥1 year of therapy. Dexrazoxane was most effective at HF prevention (Surface Under the Cumulative Ranking curve: 81.47%), and mineralocorticoid receptor antagonists were most effective at preserving LVEF (Surface Under the Cumulative Ranking curve: 99.22%).Cardiotoxicity remains a challenge for patients requiring anticancer therapies. The initiation of extended duration cardioprotection reduces incident HF. Additional head-to-head trials are needed.

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.

Global circumferential strain (GCS) and global radial strain (GRS) are reduced with cytotoxic chemotherapy. There are limited data on the effect of immune checkpoint inhibitor (ICI) myocarditis on GCS and GRS.This study aimed to detail the role of GCS and GRS in ICI myocarditis.In this retrospective study, GCS and GRS from 75 cases of patients with ICI myocarditis and 50 ICI-treated patients without myocarditis (controls) were compared. Pre-ICI GCS and GRS were available for 12 cases and 50 controls. Measurements were performed in a core laboratory blinded to group and time. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death.Cases and controls were similar in age (66 ± 15 years vs 63 ± 12 years; P = 0.20), sex (male: 73% vs 61%; P = 0.20) and cancer type (P = 0.08). Pre-ICI GCS and GRS were also similar (GCS: 22.6% ± 3.4% vs 23.5% ± 3.8%; P = 0.14; GRS: 45.5% ± 6.2% vs 43.6% ± 8.8%; P = 0.24). Overall, 56% (n=42) of patients with myocarditis presented with preserved left ventricular ejection fraction (LVEF). GCS and GRS were lower in myocarditis compared with on-ICI controls (GCS: 17.5% ± 4.2% vs 23.6% ± 3.0%; P< 0.001; GRS: 28.6% ± 6.7% vs 47.0% ± 7.4%; P< 0.001). Over a median follow-up of 30days, 28 cardiovascular events occurred. A GCS (HR: 4.9 [95%CI: 1.6-15.0]; P = 0.005) and GRS (HR: 3.9 [95%CI: 1.4-10.8]; P = 0.008) below the median was associated with an increased event rate. In receiver-operating characteristic (ROC) curves, GCS (AUC: 0.80 [95%CI: 0.70-0.91]) and GRS (AUC: 0.76 [95%CI: 0.64-0.88]) showed better performance than cardiac troponin T (cTnT) (AUC: 0.70 [95%CI: 0.58-0.82]), LVEF (AUC: 0.69 [95%CI: 0.56-0.81]), and age (AUC: 0.54 [95%CI: 0.40-0.68]). Net reclassification index and integrated discrimination improvement demonstrated incremental prognostic utility of GRS over LVEF (P = 0.04) and GCS over cTnT (P = 0.002).GCS and GRS are lower in ICI myocarditis, and the magnitude of reduction has prognostic significance.

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.

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.

The population of patients with cancer is rapidly expanding, and the diagnosis and monitoring of cardiovascular complications greatly rely on imaging. Numerous advances in the field of cardio-oncology and imaging have occurred in recent years. This review presents updated and practical approaches for multimodality cardiovascular imaging in the cardio-oncology patient and provides recommendations for imaging to detect the myriad of adverse cardiovascular effects associated with antineoplastic therapy, such as cardiomyopathy, atherosclerosis, vascular toxicity, myocarditis, valve disease, and cardiac masses. Uniquely, we address the role of cardiovascular imaging in patients with pre-existing cardiomyopathy, pregnant patients, long-term survivors, and populations with limited resources. We also address future avenues of investigation and opportunities for artificial intelligence applications in cardio-oncology imaging. This review provides a uniform practical approach to cardiovascular imaging for patients with cancer.

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.

Purpose Although advancements in cancer treatments using radiation therapy (RT) have led to improved outcomes, radiation-induced heart disease (RIHD) remains a significant source of morbidity and mortality in survivors of cancers in the chest. Currently, there are no diagnostic tests in clinical use due to a lack of understanding of the natural history and mechanisms of RIHD development. Few studies have examined the utility of using metabolomics to prospectively identify cancer survivors who are at risk of developing cardiotoxicity. Methods We analyzed plasma and left ventricle heart tissue samples collected from a cohort of male Sprague Dawley (SD) rats that were either sham irradiated or received fractionated doses (9 Gy per day × 5 days) of targeted X-ray radiation to the heart. Metabolomic and lipidomic analyses were utilized as a correlative approach for delineation of novel biomarkers associated with radiation-induced cardiac toxicity. Additionally, we used high-resolution mass spectrometry to examine the metabolomic profiles of plasma samples obtained from patients receiving high dose thoracic RT for esophageal cancer. Results Metabolic alterations in the rat model and patient plasma profiles, showed commonalities of radiation response that included steroid hormone biosynthesis and vitamin E metabolism. Alterations in patient plasma profiles were used to develop classification algorithms predictive of patients at risk of developing RIHD. Conclusion Herein, we report the feasibility of developing a metabolomics-based biomarker panel that is associated with adverse outcomes of cardiac function in patients who received RT for the treatment of esophageal cancer.

BACKGROUND Inferior vena cava filter (IVCF) use is common after a venous thromboembolic event (VTE). Cancer is associated with higher rates of VTEs and is also seen in a significant proportion of patients requiring IVCF. As hospital readmissions remain a frequently scrutinized metric, we sought to evaluate the impact of cancer on hospital-readmission rates and in-hospital outcomes among patients with VTEs who received an IVCF. METHODS Leveraging the 2013 to 2014 Nationwide Readmission Database, we identified adult patients presenting with a VTE in the United States and evaluated 30-day readmission rates and readmission in-hospital outcomes postindex-admission. Multivariable logistic regression was used to identify factors associated with readmission after an index-procedure, including traditional and nontraditional cardiovascular risk factors, as well as hospital-level characteristics. RESULTS Among the 619 241 patients presenting with a VTE at index-admission, 11.2% of patients received IVCF on index-admission, of which 30.9% had cancer. The 30-day readmission rate amongst IVCF recipients was 15.8% (N = 10 927), and 19.9% amongst those with cancer compared to 13.9% in patients without cancer (P

Background Recent clinical trials have evaluated angiotensin-converting enzyme (ACE) inhibitors (ACEis), angiotensin receptor blockers (ARBs), and beta blockers (BBs) in relation to cardiotoxicity in patients with cancer, typically defined by ejection fraction declines. However, these trials have not examined long-term, hard clinical endpoints. Within a prospective study, we examined the risk of heart failure (HF) and coronary heart disease (CHD) events in relation to use of commonly used antihypertensive medications, including ACEis/ARBs, BBs, calcium channel blockers (CCB), and diuretics, comparing women with and without cancer. Materials and Methods In a cohort of 56,997 Women's Health Initiative study participants free of cardiovascular disease who received antihypertensive treatment, we used multivariable-adjusted Cox regression models to calculate the hazard ratios (HRs) of developing CHD, HF, and a composite outcome of cardiac events (combining CHD and HF) in relation to use of ACEis/ARBs, CCBs, or diuretics versus BBs, separately in women with and without cancer. Results Whereas there was no difference in risk of cardiac events comparing ACEi/ARB with BB use among cancer-free women (HR = 0.99 [0.88–1.12]), among cancer survivors ACEi/ARB users were at a 2.24-fold risk of total cardiac events (1.18–4.24); p-interaction = .06). When investigated in relation to CHD only, an increased risk was similarly observed in ACEi/ARB versus BB use for cancer survivors (HR = 1.87 [0.88–3.95]) but not in cancer-free women (HR = 0.91 [0.79–1.06]; p-interaction = .04). A similar pattern was also seen in relation to HF but did not reach statistical significance (p-interaction = .23). Conclusion These results from this observational study suggest differing risks of cardiac events in relation to antihypertensive medications depending on history of cancer. Although these results require replication before becoming actionable in a clinical setting, they suggest the need for more rigorous examination of the effect of antihypertensive choice on long-term cardiac outcomes in cancer survivors. Implications for Practice Although additional research is needed to replicate these findings, these data from a large, nationally representative sample of postmenopausal women indicate that beta blockers are favorable to angiotensin-converting enzyme inhibitors in reducing the risk of cardiac events among cancer survivors. This differs from the patterns observed in a noncancer cohort, which largely mirrors what is found in the randomized clinical trials in the general population.

Aims Takotsubo cardiomyopathy (TC) is characterized by transient ventricular impairment, often preceded by emotional or physical stress. Racial differences affect the outcomes of several cardiovascular conditions; however, the effect of race on TC remains unknown. This investigation aims to assess the effect of race on in‐hospital outcomes of TC in a large national sample. Methods and results We conducted a US‐wide analysis of TC hospitalizations from 2006 to 2014 by querying the National Inpatient Sample database for the International Classification of Diseases‐ninth Revision TC code, characteristics, and inpatient outcomes. Patients with a primary diagnosis of acute coronary syndrome were excluded to reduce selection bias. Caucasians were compared with African Americans (AA) for differences in baseline characteristics and in‐hospital outcomes. Multivariate regression models were created to adjust for potential confounders. Of 97 650 TC patients, 83 807 (86.9%) were women, 89 624 (91.8%) identified as Caucasians, and 8026 (8.2%) as AA. The annual number of TC hospitalizations increased significantly from 2006 to 2014 in both races (from 335 to 21 265 annual cases, P < 0.001). In‐hospital mortality initially increased (1–2% in 2006 to 5–6% in 2009, P < 0.001) and subsequently remained relatively stable around 5–7% with no significant difference between races. In unadjusted analysis, AA had more cardiac arrests [304 (3.8%) vs. 2569 (2.9%), P = 0.04], invasive mechanical ventilation [1671 (20.8%) vs. 15 897 (17.7%), P = 0.002], tracheostomies [242 (3%) vs. 1600 (1.8%), P = 0.001], acute kidney injuries [1765 (22%) vs. 14 608 (16.3%), P < 0.0001], and longer hospital stays [4.5 (3.2–4.8) vs. 3.8 (3.7–3.9) days, P < 0.0001] compared with Caucasians. After the adjustment for differences in age, gender, comorbidities (using the enhanced Charlson comorbidity index), hospital location/teaching status, and socio‐economic factors, all differences were significantly attenuated or eliminated. Additionally, the adjusted risk was lower in AA compared with Caucasians, for cardiogenic shock [odds ratio (OR) 0.61 (0.47–0.78), P < 0.0001], mechanical ventilation [OR 0.8 (0.70–0.92), P = 0.002] and intraaortic balloon pump insertion [OR 0.63 (0.41–0.99), P = 0.04]. Conclusions Our investigation is the first large US‐wide analysis studying racial variations in TC outcomes. AA overall have more in‐hospital complications; however, the differences are driven by racial disparities in demographics, comorbidities, and socio‐economic factors.

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.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.

BACKGROUND: Pivotal trials of chimeric antigen receptor T-cell (CAR-T) have identified common toxicities but may have been underpowered to detect cardiovascular and pulmonary adverse events (CPAEs). OBJECTIVES: To investigate CPAEs associated with commercial CD19-directed CAR-T therapy. METHODS: In this retrospective, pharmacovigilance study we used the FDA adverse event reporting system to identify CPAEs associated with axicabtagene-ciloleucel and tisagenlecleucel. We evaluated disproportionate reporting by the reporting odds ratio (ROR) and the lower bound of the Information Component (IC) 95% credibility interval (IC(025)>0 is deemed significant). Significant associations were further adjusted to age and sex (adj.ROR). RESULTS: We identified CAR-T reports of 2,657 patients, including 546 (20.5%) CPAEs. CPAEs overlapped with cytokine release syndrome in 68.3% (373/546) of the reports. Compared to the full database, CAR-T was associated with over-reporting of tachyarrhythmias (n=74[2.8%], adj.ROR=2.78 [95% CI, 2.21–3.51]), cardiomyopathy (n=69[2.6%], adj.ROR=3.51 [2.42–5.09]), pleural disorders (n=46[1.7%], adj.ROR=3.91 [2.92–5.23]), and pericardial diseases (n=11[0.4%], adj.ROR=2.26 [1.25–4.09], all IC(025)>0). Venous-thromboembolic events (VTEs) were associated only with axicabtagene-ciloleucel therapy (n=28[1.6%], adj.ROR= 1.80 [1.24–2.62], IC(025)>0). Atrial fibrillation (n=55) was the leading tachyarrhythmia, followed by ventricular arrythmias (n=14). Tachyarrhythmias and VTEs were reported more often following axicabtagene-ciloleucel than tisagenlecleucel in an age and sex-adjusted model (adj.ROR=1.82 [1.04–3.18] and adj.ROR=2.86 [1.18–6.93], respectively). Finally, the fatality rate of CPAEs was 30.9%. CONCLUSIONS: In this largest post-marketing study to date, we identified an association between CAR-T and various CPAEs, including tachyarrhythmias, cardiomyopathy, pericardial and pleural disorders, and VTEs. Our findings should be considered in the multi-disciplinary assessment for and monitoring of CAR-T therapy recipients.

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 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.

BACKGROUND: Cancer inducing a hypercoagulable state, venous thromboembolism (VTE) remains a leading cause of morbidity and mortality globally. We assessed the impacts of cancer on the likelihood for readmission after a VTE‐targeted procedure. METHODS: We created a new cohort using discharge‐level data from all hospitalizations from State Inpatient Databases of geographically dispersed participating states (18‐27 states). RESULTS: In those presenting with VTE during index‐admission (619 241), 2.4% patients underwent catheter directed thrombolytic therapy (CDL) on index admission and among those 20.3% had cancer. Moreover, the 30‐day readmission rate amongst CDL recipients (10 776 overall) was 14.3% in those with cancer compared to 8.8% in those with no cancer history (P < .0001). Additionally, in‐hospital mortality (5.7% vs 1.1%; P = 0.009) and cost‐of‐care ($11 014 ± 914 vs $10 520 ± 534; P = .04) was significantly higher in cancer compared to noncancer. CONCLUSION: The use of CDL does not appear to reduce the risk of returning for a VTE‐related admission in cancer.

Session III of the Second International Colloquium on Cardio-Oncology focused on the diagnosis, management, and prevention of cardiovascular toxicity of cancer drugs. With a large menu of biomarkers and imaging modalities available to the cardio oncologist, there continues to be no consensus regarding the best use of each modality alone and in combination and whether we can actually prevent early and late cardiotoxicity using these tests to guide a preventive strategy. It has become increasingly clear that early diagnosis and intervention leads to less late cardiotoxicity and fewer cardiac-related events. This can be accomplished by taking a thorough history and performing a goal directed physical examination coupled with use of biomarkers and imaging studies. This session attempted to provide rationale for a current and integrated approach to these issues.

Trastuzumab targets the human epidermal growth factor receptor 2 (HER2). Its overexpression occurs in 25% of breast cancers and is associated with aggressive tumor characteristics and poor prognosis in absence of targeted therapy. Trastuzumab dramatically improves HER2-positive breast cancer outcomes; however, its clinical use is associated with left ventricular dysfunction and heart failure. Patients receiving trastuzumab or other HER2-targeted therapies undergo routine cardiac function assessment. Holding and/or stopping trastuzumab treatment in the setting of left ventricular dysfunction is recommended. This article summarizes the role of trastuzumab in cancer treatment, the mechanisms of trastuzumab-induced cardiotoxicity, recent clinical investigations, and current controversies.

Purpose HER2-targeted therapies have substantially improved the outcome of patients with breast cancer, however, they can be associated with cardiac toxicity. Guidelines recommend holding HER2-targeted therapies until resolution of cardiac dysfunction. SAFE-HEaRt is the first trial that prospectively tests whether these therapies can be safely administered without interruptions in patients with cardiac dysfunction. Methods Patients with stage I–IV HER2-positive breast cancer candidates for trastuzumab, pertuzumab or ado-trastuzumab emtansine (TDM-1), with left ventricular ejection fraction (LVEF) 40–49% and no symptoms of heart failure (HF) were enrolled. All patients underwent cardiology visits, serial echocardiograms and received beta blockers and ACE inhibitors unless contraindicated. The primary endpoint was completion of the planned HER2-targeted therapies without developing either a cardiac event (CE) defined as HF, myocardial infarction, arrhythmia or cardiac death or significant asymptomatic worsening of LVEF. The study was considered successful if planned oncology therapy completion rate was at least 30%. Results Of 31 enrolled patients, 30 were evaluable. Fifteen patients were treated with trastuzumab, 14 with trastuzumab and pertuzumab, and 2 with TDM-1. Mean LVEF was 45% at baseline and 46% at the end of treatment. Twenty-seven patients (90%) completed the planned HER2-targeted therapies. Two patients experienced a CE and 1 had an asymptomatic worsening of LVEF to ≤ 35%. Conclusion This study provides safety data of HER2-targeted therapies in patients with breast cancer and reduced LVEF while receiving cardioprotective medications and close cardiac monitoring. Our results demonstrate the importance of collaboration between cardiology and oncology providers to allow for delivery of optimal oncologic care to this unique population. Electronic supplementary material The online version of this article (10.1007/s10549-019-05191-2) contains supplementary material, which is available to authorized users.

Takotsubo cardiomyopathy (TC) is a form of dilated cardiomyopathy often associated with physical or emotional stress. Association with cancer has been reported, however, in-hospital outcomes in TC patients with history of malignancy have not been fully characterized. We conducted a retrospective chart review of hospitalized patients with diagnosis of TC between January 2006 and January 2017. Patients were divided into 2 groups based on the previous history of malignancy. Presenting symptoms, cardiac imaging and short-term events including in-hospital complications and mortality, were compared. Of 318 patients with TC, 81 (25.4%) had a previous diagnosis of cancer. Mean age was 67.5 (SD 12.6), 151 (47.5%) were African American, 122 (38.4%) Caucasian, and 10 (3.1%) of other ethnicities. Patients with history of malignancy were older (70.0 [SD 10.6] vs 66.6 [SD 13.1] years, p = 0.03), had higher heart rate on presentation (93 [SD 19] vs 87 [SD 25] beats/minute, p = 0.03), higher prevalence of severely decreased cardiac function (left ventricular ejection fraction25%) (29.6% vs 16%, p = 0.01), longer hospitalization (7 (4-13) vs 4 (3-8) days, p = 0.001) and experienced more in-hospital cardiac arrests (6 [7.4%] vs 5 [2.1%], p = 0.035) compared with patients without malignancy history. Higher percentage of longer hospitalization and left ventricular ejection fraction25% in the cancer group persisted after controlling for sepsis, chemotherapy exposure, and metastatic disease. In conclusion, in a racially diverse hospitalized population of TC, prevalence of cancer history is high, and diagnosis of previous malignancy is associated with adverse in-hospital outcomes.

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.

Takotsubo cardiomyopathy (TC) develops in patients who are under significant emotional, psychosocial, or sudden biochemical stress. However, the added burden of TC on the patients receiving chemotherapy has never been studied. We aimed to describe the additional clinical and economic burden, along with the potential predictors of TC and related in-hospital mortality in patients receiving chemotherapy using the largest inpatient cohort. We identified chemotherapy-related adult hospitalizations using the National Inpatient Sample databases (2010 to 2014). Primary end points were the incidence of TC and the odds of in-hospital mortality. Secondary end points were gender-based incidence differences, length of stay (LOS), hospital charges, and discharge disposition. We identified 1,067,977 chemotherapy-related hospitalizations, of which, 562 hospitalizations revealed TC incidence. Other co-morbidities were also significantly higher in the TC cohort. In unmatched analyses, the LOS (median 17 days vs 5 days) and total hospital charges (median $162,825 vs $46,335) were significantly higher in the TC group. A propensity-matched analysis confirmed the increased healthcare burden. Multivariate analysis revealed over 2-times higher odds (odds ratio [OR] 2.17) of in-hospital mortality in the TC group. Female gender (OR 2.48), and nonelective (OR 2.26), and nonfederal government hospital (OR 2.68) admissions had more than twice the odds of developing TC. An advanced age, Asian race, urban-teaching hospital, and complications such as septicemia, fluid-electrolyte disorders, cardiogenic shock, and respiratory failure independently raised mortality odds in the TC group. In conclusion, we observed an overall increasing nationwide trend in TC incidence in patients receiving chemotherapy, which adds to significantly increased in-hospital mortality, LOS, and healthcare charges.

Aims There is conflicting evidence whether heart failure (HF) is a risk factor for incident cancer. Despite population-based cohorts demonstrating this association, an analysis of the Physician's Health Study found no association in a cohort of mostly healthy males. We investigated the association of HF with incident cancer among a large cohort of post-menopausal women. Methods and results A prospective cohort study of 146,817 post-menopausal women age 50 to 79 years enrolled in the Women's Health Initiative from 1993-1998, and followed through 2015. The primary exposure was adjudicated incident HF diagnosis, including preserved and reduced ejection fraction in a subcohort. The primary outcome was adjudicated incident total and site-specific cancers. Hazard ratios were calculated using multivariable-adjusted Cox proportional hazard regression models. Over a median follow-up of 8.4 years, 3,272 and 17,474 women developed HF and cancer, respectively. HF developed in 235 women prior to cancer. HF was associated with subsequent incident cancer (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.11-1.48). Associations were observed for obesity-related cancers (HR 1.24 [95% CI, 1.02-1.51]), as well as lung and colorectal cancers (HR 1.58 [95% CI, 1.31-2.30], 1.52 [95% CI, 1.02-2.27], respectively). HF with preserved ejection fraction (HFpEF) (HR 1.34 [95% CI, 1.06-1.67]), but not HF reduced ejection fraction (HFrEF) (HR 0.99 [95% CI 0.74-1.34]), was associated with total cancer. Conclusion HF was associated with an increase in cancer diagnoses in post-menopausal women. This association was strongest for lung cancer. Further research is needed to appreciate the underlying mechanisms responsible for this association. This article is protected by copyright. All rights reserved.

To compare the diagnostic accuracy of CMR and FDG-PET/CT and their complementary role to distinguish benign vs malignant cardiac masses.Retrospectively assessed patients with cardiac mass who underwent CMR and FDG-PET/CT within a month between 2003 and 2018.72 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).Although CMR and FDG-PET/CT can independently diagnose benign and malignant masses, the combination of these modalities provides complementary value in select cases.背景: 本研究旨在比较心脏磁共振 (CMR) 和FDG-PET/CT的诊断准确性及其在鉴别心脏良恶性肿瘤中的互补作用。 方法: 本研究回顾性地纳入了2003-2018年间在本中心被诊断为心脏肿瘤的患者, 所有患者CMR和FDG-PET/CT检查均在一个月内完成。 结果: 本研究纳入了72例同时接受了CMR和FDG-PET/CT检查的患者。其中25例 (35%) 患者被诊断为心脏良性肿瘤, 47例 (65%) 患者被诊断为心脏恶性肿瘤。在所有72例患者中, 56例 (9例良性和47例恶性) 有组织学诊断的证据。CMR和FDG-PET/CT在鉴别心脏良性和恶性肿瘤方面具有较高的准确性。其中CMR的特点表现为较高的敏感性 (98%), 而当FDG摄取为SUVmax/血池≥ 3.0时, FDG-PET/CT有较高的特异性 (88%)。结合多种CMR特征 (4种) 和FDG摄取程度 (SUVmax/血池比率≥ 3.0) 用于心脏恶性肿瘤的诊断时, 其敏感性为85%, 特异性为88%。平均随访2.6年后 (IQR:0.3-3.8年), CMR表现为边界浸润 (调整后HR=3.1; 95%可信区间: 1.5-6.5; p=0.002) 或局灶性心脏外FDG摄取 (校正HR=3.8; 95%可信区间: 1.9-7.7; p0.001) 的患者, 风险校正后的死亡率最高。 结论: 尽管CMR和FDG-PET/CT可以独立地用于诊断心脏良性和恶性肿瘤, 但在某些特定病例中, 将这两种方法结合具有互补的诊断价值。.Comparar la precisión diagnóstica de la RMC y del PET/CT con FDG y su función complementaria para distinguir entre masas cardíacas benignas y malignas. MéTODOS: Pacientes evaluados retrospectivamente con masas cardíacasque se sometieron a RMC y a PET/CT con FDG en un periodo de 1 mes entre 2003-2018.Se incluyeron 72 pacientes a los que se les realizó RMC y PET/CT con FDG. 25 pacientes (35%) fueron diagnosticados como masas benignas y 47 (65%) como masas malignas. 56 pacientes tuvieron correlación histológica: 9 masas benignas y 47 malignas.La RMC y el PET/CT con FDG tuvieron una alta precisión en la diferenciación de masas benignas de malignas, algunas caracteristicas de la RMC demostraron una mayor sensibilidad (98 %), mientras que una captación de FDG (SUVmax/poolsanguíneo ≥ 3.0)demostró una alta especificidad (88%). Combinando múltiples (4) características de la RMC con la captación de FDG (SUVmax/poolsanguíneo ≥ 3,0)se obtuvo una sensibilidad del 85% y una especificidad del 88 % para diagnosticar masas malignas. Durante un seguimiento promedio de 2.6 años (ICR: 0.3-3.8 años), la mortalidad ajustada por riesgo fue más alta entre los pacientes con un borde infiltrante en la RMC (HR ajustado = 3.1; IC del 95 %: 1.5-6.5;p=0.002) o captación extracardiaca focal de FDG (HR ajustado=3.8; IC 95%: 1.9-7.7; p0.001). CONCLUSIóN: Aunque la RMC y el PET/CT con FDG pueden diagnosticar de forma independiente masas benignas y malignas, la combinación de estas modalidades proporciona un valor complementario en casos seleccionados.

Results of observational studies of the association between dietary fat and risk of invasive breast cancer have been inconsistent. In the Women's Health Initiative dietary modification (DM) randomized trial designed to lower fat intake, the intervention was not associated with a statistically significant reduction of overall breast cancer risk. However, the DM association with risk of ductal carcinomaA total of 48,835 postmenopausal women, ages 50-79 years at enrollment, with no breast cancer history and ≥32% of total energy intake from fat, were randomly assigned either to a dietary intervention (During 18.7 years (median) cumulative follow-up, including intervention (∼8.7 years) and post-intervention phases (∼13.0 years), 817 DCIS cases were ascertained. No evidence of an association between the DM intervention and DCIS risk was observed overall, or by trial phase (intervention and post-intervention). Similarly, no associations were found in subgroups defined by potential risk factors for DCIS.DM aiming to reduce fat intake was not associated with altered risk of DCIS.These results do not provide evidence of an association between dietary fat reduction and the risk of DCIS among postmenopausal women.

Cancer and cardiovascular disease share many risk factors. Due to improved survival of patients with cancer, the cohort of cancer survivors with heart failure referred for heart transplantation (HT) is growing. Specific considerations include time interval between cancer treatment and HT, risk for recurrence and risk for de novo malignancy (dnM). dnM is an important cause of post-HT morbidity and mortality, with nearly a third diagnosed with malignancy by 10 years post-HT. Compared with the age-matched general population, HT recipients have an approximately 2.5-fold to 4-fold increased risk of developing cancer. HT recipients with prior malignancy show variable cancer recurrence rates, depending on years in remission before HT: 5% recurrence if >5 years in remission, 26% recurrence if 1–5 years in remission and 63% recurrence if

International audience; BACKGROUND Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.OBJECTIVES This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.METHODS In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block.RESULTS Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 +/- 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction

Precision medicine has ushered in a new era of targeted treatments for numerous malignancies, leading to improvements in overall survival. Unlike traditional chemotherapy, many molecular targeted antineoplastic agents are available in oral formulation, leading to enhanced patient convenience and a perception of reduced risk of adverse effects. Although oral antineoplastic agents are generally well-tolerated, cardiovascular toxicities are being reported with increasing frequency in part due to U.S. Food and Drug Administration and manufacturer recommended cardiac monitoring. Monitoring strategies have focused on left ventricular dysfunction, hypertension, and QT prolongation/arrhythmias. Given the rapid pace of development and availability of new oral antineoplastic agents, the purpose of this review is to provide clinicians with an up-to-date practical approach to monitoring and management of cardiovascular toxicities with the aim of improving overall outcomes for patients with cancer.

Uzdužna deformacija slobodnog zida desne klijetke u pacijenata s akutnim dekompenziranim srčanim zatajivanjem ishemijske i neishemijske etiologije Disfunkcija desne klijetke (RV) je pretkazatelj neželjnih ishoda u pacijenata sa zatajivanjem srca i reduciranom ejekcijskom frakcijom (HFrEF), međutim razlike u ehokardiografskim parametrima funkcije RV u HFrEF pacijenata s ishemijskom (ICM) i neishemijskom (NICM) kardiomiopatijom su još uvijek nedovoljno istražene. Stoga smo istraživali ehokardiografske osobitosti, uključujući uzdužnu deformaciju slobodnog zida desne klijetke (RVfwLS), u pacijenata s akutnim dekompenziranim srčanim zatajivanjem (ADHF) obzirom na etiologiju srčanog zatajivanja. Uzastopno hospitalizirani pacijenti s ADHF-om i funkcionalnim statusom NYHA III-IV su prospektivno uključivani u istraživanje ukoliko su imali LVEF

BackgroundMyocarditis is a highly morbid complication of immune checkpoint inhibitor (ICI) use that remains inadequately characterized. The QRS duration and the QTc interval are standardized electrocardiographic measures that are prolonged in other cardiac conditions; however, there are no data on their utility in ICI myocarditis.MethodsFrom an international registry, ECG parameters were compared between 140 myocarditis cases and 179 controls across multiple time points (pre-ICI, on ICI prior to myocarditis, and at the time of myocarditis). The association between ECG values and major adverse cardiac events (MACE) was also tested.ResultsBoth the QRS duration and QTc interval were similar between cases and controls prior to myocarditis. When compared with controls on an ICI (93±19 ms) or to baseline prior to myocarditis (97±19 ms), the QRS duration prolonged with myocarditis (110±22 ms, pConclusionsThe QRS duration is increased in ICI myocarditis and is associated with increased MACE risk. Use of this widely available ECG parameter may aid in ICI myocarditis diagnosis and risk-stratification.

Objective\ud To assess the temporal trends, patient characteristics and comorbidities, and in-hospital cardiovascular and obstetric complications and outcomes of pregnant women with current or historical cancer diagnosis at the time of admission for delivery.\ud \ud Patients and Methods\ud We analysed delivery hospitalisations with or without current or historical cancer between January 1, 2004 and December 31, 2014 from the United States National Inpatient Sample database. \ud \ud Results\ud We included 43,132,097 delivery hospitalisations with no cancer, 39,118 with current cancer and 67,336 with historical diagnosis of cancer. The five most common types of current cancer were haematological, thyroid, cervical, skin and breast cancer. Women with current and historical cancer were older (29 and 32 vs. 27 years) and incurred higher hospital costs ($4,131 and $4,078 vs. $3,521), compared to women without cancer. Most of the cancer types were associated with preterm birth (haematological: adjusted odds ratio (aOR) 1.48, 95% confidence interval (CI) 1.35-1.62; cervical: aOR 1.47, 95% CI 1.32-1.63; breast: aOR 1.93, 95% CI 1.72-2.16). Current haematological cancer was associated with the highest risk of peripartum cardiomyopathy (aOR 12.19, 95% CI 7.75-19.19), all-cause mortality (aOR 6.50, 95% CI 2.22-19.07), arrhythmia (aOR 3.82, 95% CI 2.04-7.15) and postpartum haemorrhage (aOR 1.31, 95% CI 1.11-1.54). Having current or historical cancer diagnosis did not confer additional risk for stillbirth; however metastases increased the risk of maternal mortality and preterm birth.\ud \ud Conclusion\ud Women with current or historical diagnosis of cancer at delivery have more comorbidities compared to women without cancer. Clinicians should communicate the risks of multi-system complications to this complex patient group.

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.

Giant cell myocarditis is a rare, often rapidly progressive and potentially fatal, disease due to T-cell lymphocyte-mediated inflammation of the myocardium that typically affects young and middle-aged adults. Frequently, the disease course is marked by acute heart failure, cardiogenic shock, intractable ventricular arrhythmias, and/or heart block. Diagnosis is often difficult due to its varied clinical presentation and overlap with other cardiovascular conditions. Although cardiac biomarkers and multimodality imaging are often used as initial diagnostic tests, endomyocardial biopsy is required for definitive diagnosis. Combination immunosuppressive therapy, along with guideline-directed medical therapy, has led to a paradigm shift in the management of giant cell myocarditis resulting in an improvement in overall and transplant-free survival. Early diagnosis and prompt management can decrease the risk of transplantation or death, which remain common in patients who present with cardiogenic shock.

Aims Primary percutaneous coronary intervention (pPCI) is the gold standard, guideline-recommended revascularization strategy in patients presenting with ST-elevation myocardial infarction (STEMI). However, there are limited data on its use and effectiveness among patients with active cancer presenting with STEMI. Methods and results All STEMI hospitalizations between 2004 and 2015 from the National Inpatient Sample were retrospectively analysed, stratified by cancer type. Propensity score matching was performed to estimate the average treatment effect of pPCI in each cancer on in-hospital adverse events, including major adverse cardiovascular and cerebrovascular events (MACCE) and its individual components, and compare treatment effect between cancer and non-cancer patients. Out of 1 870 815 patients with STEMI, 38 932 (2.1%) had a current cancer diagnosis [haematological: 11 251 (28.9% of all cancers); breast: 4675 (12.0%); lung: 9538 (24.5%); colon: 3749 (9.6%); prostate: 9719 (25.0%)]. Patients with cancer received pPCI less commonly than those without cancer (from 54.2% for lung cancer to 70.6% for haematological vs. 82.3% in no cancer). Performance of pPCI was strongly associated with lower adjusted probabilities of MACCE and all-cause mortality in the cancer groups compared with the no cancer group. There was no significant difference in estimated average pPCI treatment effect between the cancer groups and non-cancer group. Conclusion Primary percutaneous coronary intervention is underutilized in STEMI patients with current cancer despite its significantly lower associated rates of in-hospital all-cause mortality and MACCE that is comparable to patients without cancer. Further work is required to assess the long-term benefit and safety of pPCI in this high-risk group.

Introduction: myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). While corticosteroids are the cornerstones of the treatment, there are no data to guide the dose and timing. Methods: from an international registry of patients with ICI myocarditis diagnosed between 2013 and 2019, data on the type, dose (in methylprednisolone equivalent dose) and timing of steroids were extracted. Major cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically-significant complete heart block. Results: in total, 143 ICI myocarditis patients (67±13 years old, 29% women) were included. Among them, 125 received corticosteroids (87%), with the initial agent being either methylprednisolone (95, 76%), prednisone (25, 20%), hydrocortisone (2, 1.6%) or dexamethasone (3, 2.4%). The rates of overall MACE (by admission time tertile 1: 45.8%, tertile 2: 43.8%, tertile 3: 38.3%, P=0.746) and individual elements of MACE were unchanged from 2013 to 2019. The initial corticosteroid dose was categorized as low (500mg). There was an inverse relationship between the occurrence of MACE and initial dose of corticosteroid, where MACE declined with increasing doses (low 61.9%, intermediate 54.6%, high 20.4%, P72 hours (85.7%, P

The innovative development of cancer therapies has led to an unprecedented improvement in survival outcomes and a wide array of treatment-related toxicities, including those that are cardiovascular in nature. Aging of the population further adds to the number of patients being treated for cancer, especially those with comorbidities. Such pre-existing and developing cardiovascular diseases pose some of the greatest risks of morbidity and mortality in patients with cancer. Addressing the complex cardiovascular needs of these patients has become increasingly important, resulting in an imperative for an intersecting discipline: cardio-oncology. Over the past decade, there has been a remarkable rise of cardio-oncology clinics and service lines. This development, however, has occurred in a vacuum of standard practice and training guidelines, although these are being actively pursued. In this council perspective document, the authors delineate the scope of practice in cardio-oncology and the proposed training requirements, as well as the necessary core competencies. This document also serves as a roadmap toward confirming cardio-oncology as a subspecialty in medicine.

Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups using 1 degree of freedom (1df) interaction and 2df joint tests. Primary multi-ancestry analyses in 62,969 individuals in stage 1 identified 3 novel loci that were replicated in an additional 59,296 individuals in stage 2, including rs7955964 (FIGNL2/ANKRD33) showing significant 1df interactions with long sleep duration and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) showing significant 1df interactions with short sleep duration (Pint < 5×10−8). Secondary ancestry-specific two-stage analyses and combined stage 1 and 2 analyses additionally identified 23 novel loci that need external replication, including 3 and 5 loci showing significant 1df interactions with long and short sleep duration, respectively (Pint < 5×10−8). Multiple genes mapped to our 26 novel loci have known functions in sleep-wake regulation, nervous and cardiometabolic systems. We also identified new gene by long sleep interactions near five known BP loci (≤1Mb) including NME7, FAM208A, MKLN1, CEP164, and RGL3/ELAVL3 (Pint < 5×10−8). This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.

In response to the coronavirus disease 2019 (COVID-19) pandemic, the Cardio-Oncology and Imaging Councils of the American College of Cardiology offers recommendations to clinicians regarding the cardiovascular care of cardio-oncology patients in this expert consensus statement. Cardio-oncology patients—individuals with an active or prior cancer history and with or at risk of cardiovascular disease—are a rapidly growing population who are at increased risk of infection, and experiencing severe and/or lethal complications by COVID-19. Recommendations for optimizing screening and monitoring visits to detect cardiac dysfunction are discussed. In addition, judicious use of multimodality imaging and biomarkers are proposed to identify myocardial, valvular, vascular, and pericardial involvement in cancer patients. The difficulties of diagnosing the etiology of cardiovascular complications in patients with cancer and COVID-19 are outlined, along with weighing the advantages against risks of exposure, with the modification of existing cardiovascular treatments and cardiotoxicity surveillance in patients with cancer during the COVID-19 pandemic.

Heart failure and breast cancer have shared risks and morbidities. Multimodality therapies for breast cancer, including conventional chemotherapy, targeted therapeutics, radiation therapy, and hormonal agents, may make patients more susceptible to asymptomatic left ventricular dysfunction and clinical heart failure during and after treatment. New or preexisting left ventricular dysfunction may lead to interruptions in cancer treatment and limit options of breast cancer systemic therapy, leading to adverse outcomes. Early recognition and management of cardiovascular risk factors before, during, and after cancer treatment are of utmost importance. This review presents advances, challenges, and opportunities for cardiovascular care in contemporary breast cancer treatment.

Učinak sakubitril/valsartana na funkciju lijeve klijetke nakon 3 mjeseca liječenja u pacijenata s akutnim dekompenziranim srčanim zatajivanjem Podaci o učinku sakubitril/valsartana na ehokardiografske parametre u pacijenata s akutnim dekompenziranim srčanim zatajivanjem (ADHF) su još uvijek manjkavi u dostupnoj literaturi. Prospektivno smo uključili 68 uzastopnih pacijenata hospitaliziranih zbog ADHF-a, koji su liječeni sakubitril/valsartanom (N=34, S/V grupa) ili terapijom baziranoj na inhibiciji angiotenzina (N=34, ACEi/ARB grupa). Dvodimenzionalna speckle- tracking ehokardiografska (2D-STE) analiza je urađena pri uključivanju u istraživanje i nakon 3 mjeseca liječenja. Promjene u parametrima 2D-STE, uključujući globalnu uzdužnu longitudinalnu deformaciju lijeve klijetke (LVGLS), su uspoređivane među grupama t-testom i ANCOVA-om. Nije bilo značajnih razlika u bazalnim demografskim, kliničkim i ehokardiografskim osobitostima među grupama. Nakon 3 mjeseca liječenja zabilježeno je značajno poboljšanje LVEF-a i LVGLS-a u S/V grupi (prosječni porast LVEF od 27 % na 34.5 % i LVGLS od -6.6 % na -9.4 %), ali ne i u ACEi/ARB grupi. Navedeno poboljšanje LVEF-a i LVGLS-a je bilo izraženije u onih s neishemijskom etiologijom srčanog zatajivanja.

Advances in cancer screening and improved treatment approaches have led to an increase in survivorship and, consequently, recognition of an association between cancer treatments and the development of cardiovascular complications. In addition, as the population becomes proportionally older, comorbid cardiovascular risk factors are more prevalent in the population and compound the risk of developing cancer treatment–related cardiovascular toxicity. Cardio-oncology has emerged as a new subspecialty of medicine that provides a multidisciplinary approach, bringing together oncologists, cardiologists, and allied health care providers who are tasked with optimizing the cardiovascular health of patients exposed to potentially cardiotoxic cancer therapy. Using a case-based approach, practical advice on how to identify, monitor, and treat patients with cancer who are at risk for developing cancer treatment–related cardiovascular dysfunction is discussed. Cardiovascular risk factors (e.g., age, hypertension, diabetes) and cancer therapies (chemotherapy, targeted therapy, radiation) associated with cardiovascular toxicity are presented. Current cardiac monitoring strategies such as two- and three-dimensional echocardiography, cardiac MRI, and biomarkers (troponin and brain natriuretic peptide [BNP]) are discussed. Last, the current literature on pharmacologic (e.g., angiotensin-converting enzyme inhibitors, β-blockers, statins) and lifestyle (diet and exercise) strategies to mitigate cardiovascular toxicity during and following completion of cancer therapy are reviewed.

Author(s): Zhang, Lili; Awadalla, Magid; Mahmood, Syed S; Nohria, Anju; Hassan, Malek Z O; Thuny, Franck; Zlotoff, Daniel A; Murphy, Sean P; Stone, James R; Golden, Doll Lauren Alexandra; Alvi, Raza M; Rokicki, Adam; Jones-O'Connor, Maeve; Cohen, Justine V; Heinzerling, Lucie M; Mulligan, Connor; Armanious, Merna; Barac, Ana; Forrestal, Brian J; Sullivan, Ryan J; Kwong, Raymond Y; Yang, Eric H; Damrongwatanasuk, Rongras; Chen, Carol L; Gupta, Dipti; Kirchberger, Michael C; Moslehi, Javid J; Coelho-Filho, Otavio R; Ganatra, Sarju; Rizvi, Muhammad A; Sahni, Gagan; Tocchetti, Carlo G; Mercurio, Valentina; Mahmoudi, Michael; Lawrence, Donald P; Reynolds, Kerry L; Weinsaft, Jonathan W; Baksi, A John; Ederhy, Stephane; Groarke, John D; Lyon, Alexander R; Fradley, Michael G; Thavendiranathan, Paaladinesh; Neilan, Tomas G | Abstract: 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.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.These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis.

Aims To study the outcomes of cancer patients undergoing cardiac implantable electronic device (CIED) implantation. Methods and results De novo CIED implantations (2004–15; n = 2 670 590) from the National Inpatient Sample were analysed for characteristics and in-hospital outcomes, stratified by presence of cancer (no cancer, historical and current cancers) and further by current cancer type (haematological, lung, breast, colon, and prostate). Current and historical cancer prevalence has increased from 3.3% to 7.8%, and 5.8% to 7.8%, respectively, between 2004 and 2015. Current cancer was associated with increased adjusted odds ratio (OR) of major adverse cardiovascular events (MACE) [composite of all-cause mortality, thoracic and cardiac complications, and device-related infection; OR 1.26, 95% confidence interval (CI) 1.23–1.30], all-cause mortality (OR 1.43, 95% CI 1.35–1.50), major bleeding (OR 1.38, 95% CI 1.32–1.44), and thoracic complications (OR 1.39, 95% CI 1.35–1.43). Differences in outcomes were observed according to cancer type, with significantly worse MACE, mortality and thoracic complications with lung and haematological malignancies, and increased major bleeding in colon and prostate malignancies. The risk of complications was also different according to CIED subtype. Conclusion The prevalence of cancer patients amongst those undergoing CIED implantation has significantly increased over 12 years. Overall, current cancers are associated with increased mortality and worse outcomes, especially in patients with lung, haematological, and colon malignancies whereas there was no evidence that historical cancer had a negative impact on outcomes.

PURPOSE Observational studies of dietary fat intake and breast cancer have reported inconsistent findings. This topic was addressed in additional analyses of the Women’s Health Initiative (WHI) Dietary Modification (DM) clinical trial that evaluated a low-fat dietary pattern influence on breast cancer incidence. METHODS In the WHI DM trial, 48,835 postmenopausal women, ages 50-79 years, with no prior breast cancer, and a dietary fat intake of ≥ 32% of energy were randomly assigned at 40 US centers to a usual diet comparison group (60%) or dietary intervention group (40%). The goals were to reduce fat intake to 20% of energy and increase vegetable, fruit, and grain intake. Breast cancers were confirmed after central medical record review and serial National Death Index linkages to enhance mortality findings. RESULTS During 8.5 years of dietary intervention, breast cancer incidence and deaths as a result of breast cancer were nonsignificantly lower in the intervention group, while deaths after breast cancer were statistically significantly lower both during intervention and through a 16.1-year (median) follow-up. Now, after a long-term, cumulative 19.6-year (median) follow-up, the significant reduction in deaths after breast cancer persists (359 [0.12%] v 652 [0.14%] deaths; hazard ratio [HR], 0.85; 95% CI, 0.74 to 0.96; P = .01), and a statistically significant reduction in deaths as a result of breast cancer (breast cancer followed by death attributed to the breast cancer) emerged (132 [0.037%, annualized risk] v 251 [0.047%] deaths, respectively; HR, 0.79; 95% CI, 0.64 to 0.97; P = .02). CONCLUSION Adoption of a low-fat dietary pattern associated with increased vegetable, fruit, and grain intake, demonstrably achievable by many, may reduce the risk of death as a result of breast cancer in postmenopausal women.

The immune checkpoint inhibitors have brought about a paradigm shift in the treatment of many cancers and are being used as the first line therapy in increasing number of aggressive malignancies, including metastatic melanoma. Their adverse effects, mostly mediated by an uncontrolled overactivation of the immune system, may compromise the therapeutic benefit. Combination immune checkpoint therapies in particular, have higher therapeutic efficacy, but have also been associated with a higher incidence of severe immune-related adverse effects including autoimmune lymphocytic myocarditis. Recent clinical reports of this rare and life threatening condition indicated rapid progression of severe hemodynamic and electrical instability, with or without acute decompensated heart failure, reduced ejection fraction and shock, pointing to the need for early recognition, diagnosis and prompt management. Current guidelines for management of other immune-related adverse effects recommend high-dose glucocorticoids, with consideration of immunomodulators, such as infliximab in patients with severe colitis. However, knowledge about the treatment approaches in immune-related myocarditis remains extremely scarce. Here we report a case of severe, steroid refractory, lymphocytic myocarditis that occurred after the first cycle of combination immunotherapy with the programmed cell death protein-1 inhibitor, nivolumab, and the cytotoxic T-lymphocyte-associated protein 4 blocker, ipilimumab, for metastatic melanoma. We discuss treatment approaches including the role for transvenous pacemaker, advanced heart failure support, and interdisciplinary decision making.

Early recognition of cancer therapy-related cardiac dysfunction (CTRCD) provides an opportunity to mitigate cardiac injury and risk of developing late cardiac events. Echocardiography serves as the cornerstone in the detection and surveillance of CTRCD in patients during and after cancer therapy. Guidelines from professional societies and regulatory agencies have been published on approaches to surveillance, diagnosis, and treatment of CTRCD, although adoption as standard of care remains limited given the lack of evidence on the prognostic value of asymptomatic left ventricular (LV) dysfunction in the oncology population. The frequency of cardiac monitoring and the appropriateness of the Food and Drug Administration (FDA)-recommended cardiac monitoring schedule in all patients receiving trastuzumab for breast cancer has been challenged. Interruption versus continuation of oncological therapy in the setting of asymptomatic LV dysfunction remains a clinical conundrum given the uncertain balance of the risk of cardiac dysfunction and benefit of oncology efficacy. Despite their limitations, echocardiographic measures of LV function continue to play a pivotal role in clinical decision making, with global longitudinal strain emerging as a promising tool in informing and facilitating the selection of cancer treatment and optimizing cardiovascular outcomes. This review highlights the key recommendations of the existing guidelines and discusses recent developments in cardio-oncology imaging practices with the aim of providing practical guidance on the role and use of echocardiography in challenging clinical cases in cardio-oncology.

Background Human epidermal growth receptor 2 (HER2) targeted therapies have survival benefit in adjuvant and metastatic HER2 positive breast cancer but are associated with cardiac dysfunction. Current U.S. Food and Drug Administration recommendations limit the use of HER2 targeted agents to patients with normal left ventricular (LV) systolic function. Methods The objective of the SAFE-HEaRt study is to evaluate the cardiac safety of HER2 targeted therapy in patients with HER2 positive breast cancer and mildly reduced left ventricular ejection fraction (LVEF) with optimized cardiac therapy. Thirty patients with histologically confirmed HER2 positive breast cancer (stage I-IV) and reduced LVEF (40% to 49%) who plan to receive HER2 targeted therapy for ≥3 months will be enrolled. Prior to initiation on study, optimization of heart function with beta-blockers and angiotensin converting enzyme inhibitors will be initiated. Patients will be followed by serial echocardiograms and cardiac visits during and 6 months after completion of HER2 targeted therapy. Myocardial strain and blood biomarkers, including cardiac troponin I and high-sensitivity cardiac troponin T, will be examined at baseline and during the study. Discussion LV dysfunction in patients with breast cancer poses cardiac and oncological challenges and limits the use of HER2 targeted therapies and its oncological benefits. Strategies to prevent cardiac dysfunction associated with HER2 targeted therapy have been limited to patients with normal LVEF, thus excluding patients who may receive the highest benefit from those strategies. SAFE-HEaRt is the first prospective pilot study of HER2 targeted therapies in patients with reduced LV function while on optimized cardiac treatment that can provide the basis for clinical practice changes. The Oncologist 2017;22:518-525 IMPLICATIONS FOR PRACTICE: Human epidermal growth receptor 2 (HER2) targeted therapies have survival benefit in adjuvant and metastatic HER2 positive breast cancer but are associated with cardiac dysfunction. To our knowledge, SAFE-HEaRt is the first clinical trial that prospectively tests the hypothesis that HER2 targeted therapies may be safely administered in patients with mildly reduced cardiac function in the setting of ongoing cardiac treatment and monitoring. The results of this study will provide cardiac safety data and inform consideration of clinical practice changes in patients with HER2 positive breast cancer and reduced cardiac function, as well as provide information regarding cardiovascular monitoring and treatment in this population.