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BACKGROUND: Exposure to fine particulate matter (<2.5 um, particulate matter with an aerodynamic diameter <2.5 microns [PM2.5]) has been implicated in atherogenesis. Limited data in animal studies suggest that PM2.5 exposure leads to myocardial fibrosis and increased incidence of heart failure (HF). Whether PM2.5 is associated with adverse outcomes in patients with preexisting HF has not been widely studied. METHODS AND RESULTS: In this retrospective cohort study, Medicare patients hospitalized with first HF between 2013 and 2020 were identified from the Medicare Provider Analysis and Review Part A 100% files. Patients were linked with integrated estimates of ambient PM2.5 obtained at 1×1 km using the zip code of participants' residence. The study outcomes were all-cause death, HF, and all-cause readmissions burden. A total of 2 599 525 patients were included in this study, with 6 321 731 person-years of follow-up. Mean PM2.5 was 7.3±1.7 µg/m3. Each interquartile range of PM2.5 was associated with 0.9% increased hazard of all-cause death, 4.5% increased hazard of first HF readmission, 3.1% increased risk of HF hospitalization burden, and 5.2% increase in all-cause readmission burden, after adjusting for 11 sociodemographic and medical factors. Subgroup analyses showed that the effects were more pronounced at levels <7 µg/m3 and in patients aged <75 years, Asians, and those residing in rural areas. CONCLUSIONS: Ambient air pollution is associated with higher risk of adverse events in Medicare beneficiaries with established HF. These associations persist below the National Air Quality Standards (12 µg/m3), supporting that no threshold effect exists for health effects of air pollution exposure.
Subject(s)
Air Pollution , Environmental Exposure , Heart Failure , Medicare , Particulate Matter , Patient Readmission , Humans , Heart Failure/epidemiology , United States/epidemiology , Female , Male , Aged , Retrospective Studies , Particulate Matter/adverse effects , Air Pollution/adverse effects , Aged, 80 and over , Environmental Exposure/adverse effects , Patient Readmission/statistics & numerical data , Risk Factors , Risk Assessment , Incidence , Air Pollutants/adverse effects , Cause of DeathABSTRACT
The long-term survivorship of patients diagnosed with cancer has improved due to accelerated detection and rapidly evolving cancer treatment strategies. As such, the evaluation and management of cancer therapy related complications has become increasingly important, including cardiovascular complications. These have been captured under the umbrella term "cardiotoxicity" and include left ventricular dysfunction and heart failure, acute coronary syndromes, valvular abnormalities, pericardial disease, arrhythmia, myocarditis, and vascular complications. These complications add to the burden of cardiovascular disease (CVD) or are risk factors patients with cancer treatment are presenting with. Of note, both pre- and newly developing CVD is of prognostic significance, not only from a cardiovascular perspective but also overall, potentially impacting the level of cancer therapy that is possible. Currently, there are varying recommendations and practices regarding CVD risk assessment and mitigating strategies throughout the cancer continuum. This article provides an overview on this topic, in particular, the role of cardiac imaging in the care of the patient with cancer. Furthermore, it summarizes the current evidence on the spectrum, prevention, and management of chemotherapy-related adverse cardiac effects.
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Cancer and cardiovascular disease are the two most common causes of death worldwide. As the fields of cardiovascular medicine and oncology continue to expand, the area of overlap is becoming more prominent demanding dedicated attention and individualized patient care. We have come to realize that both fields are inextricably intertwined in several aspects, so much so that the mere presence of one, with its resultant downstream implications, has an impact on the other. Nonetheless, cardiovascular disease and cancer are generally approached independently. The focus that is granted to the predominant pathological entity (either cardiovascular disease or cancer), does not allow for optimal medical care for the other. As a result, ample opportunities for improvement in overall health care are being overlooked. Herein, we hope to shed light on the interconnected relationship between cardiovascular disease and cancer and uncover some of the unintentionally neglected intricacies of common cardiovascular therapeutics from an oncologic standpoint.
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BACKGROUND: CT- coronary calcium score, is one of the most studied and widely available modalities in cardiovascular medicine. Coronary artery calcium score (CACS) is an established predictor of coronary artery disease. The 'standard of care' diagnostic modality to measure CACS is ECG-gated Cardiac Multi-Detector Computed Tomography. There is convincing evidence of a strong association between CACS and major cardiovascular (CV) events in asymptomatic individuals. Cancer patients (C) may have a higher risk for CV disease than non-cancer patients (NC) related not only to cancer treatments but also to shared biological factors and pathways. Thus, identifying tools for early detection of CV disease in this population is of utmost importance. METHODS: A retrospective cohort analysis was performed with patients from Cleveland Clinic Florida and Ohio who had CACS from 2017 to 2021. Patients who had cancer diagnosis prior to CACS were matched to NC for age and sex. CV events after their index CACS events were compared between C and NC, and matched control and propensity analysis were conducted. RESULTS: Ten thousand seven hundred forty-two patients had CACS; 703 cancer patients had CACS and were eligible. Extensive CACS (> 400) were significantly higher in cancer, 94 (13.37%) vs non-cancer patients, 76 (10.83%), P = 0.011. Furthermore, after propensity matched analysis, CACS > 400 was 14.8% in C vs 9.6% in NC, P = < 0.05. CV events were similar in both cohorts (p = NS), despite less CV risk factors in cancer patients (P = < 0.05). For the combined moderate (101-400) & extensive (> 400) CACS, the prevalence of stroke and peripheral arterial disease, a marker of systemic atherosclerosis, was significantly higher in patients with cancer (P < 0.01). CONCLUSIONS: Despite having fewer CV risk factors in our study, similar CACS in cancer patients are suggestive of a higher prevalence of CV disease independent of traditional risk factors. High CACS and the overall prevalence of vascular events were more frequent in patients with cancer. Higher prevalence of peripheral arterial disease and cerebrovascular accident further suggests the increased atherosclerotic burden in C.
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BACKGROUND: Global collaboration in cardio-oncology is needed to understand the prevalence of cancer therapy-related cardiovascular toxicity in different risk groups, practice settings, and geographic locations. There are limited data on the socioeconomic and racial/ethnic disparities that may impact access to care and outcomes. To address these gaps, we established the Global Cardio-Oncology Registry, a multinational, multicenter prospective registry. METHODS: We assembled cardiologists and oncologists from academic and community settings to collaborate in the first Global Cardio-Oncology Registry. Subsequently, a survey for site resources, demographics, and intention to participate was conducted. We designed an online data platform to facilitate this global initiative. RESULTS: A total of 119 sites responded to an online questionnaire on their practices and main goals of the registry: 49 US sites from 23 states and 70 international sites from 5 continents indicated a willingness to participate in the Global Cardio-Oncology Registry. Sites were more commonly led by cardiologists (85/119; 72%) and were more often university/teaching (81/119; 68%) than community based (38/119; 32%). The average number of cardio-oncology patients treated per month was 80 per site. The top 3 Global Cardio-Oncology Registry priorities in cardio-oncology care were breast cancer, hematologic malignancies, and patients treated with immune checkpoint inhibitors. Executive and scientific committees and specific committees were established. A pilot phase for breast cancer using Research Electronic Data Capture Cloud platform recently started patient enrollment. CONCLUSIONS: We present the structure for a global collaboration. Information derived from the Global Cardio-Oncology Registry will help understand the risk factors impacting cancer therapy-related cardiovascular toxicity in different geographic locations and therefore contribute to reduce access gaps in cardio-oncology care. Risk calculators will be prospectively derived and validated.
Subject(s)
Breast Neoplasms , Cardiologists , Cardiology , Neoplasms , Humans , Female , Neoplasms/diagnosis , Neoplasms/epidemiology , Neoplasms/therapy , Medical Oncology , Registries , Multicenter Studies as TopicABSTRACT
BACKGROUND: Immune checkpoint inhibitors can result in overlap syndrome comprised of myasthenia gravis, myositis and myocarditis. However, the mortality predictors have not been clearly delineated. METHODS: We examined the characteristics of 11 patients diagnosed with overlap syndrome at Cleveland Clinic. All the available clinical, diagnostic, biochemical and disease specific factors were examined. Clinical predictors of increased mortality were using student t-test for parametric data and Wilcoxon-signed rank testing for nonparametric data. RESULTS: Seven patients out of eleven patients were alive during the analysis. Our study did confirm that troponins were indicator of early demise. However, study showed that elevated creatinine, BUN, and decreased hemoglobin were also observed in patients who met early demise. Unlike previously published studies, elevated NT Pro-BNP and reduced left ventricular ejection fraction were not a seen in this study. However, there were higher incidence of electrical abnormalities in deceased patients when compared to alive. CONCLUSION: Our study is first to examine various clinical parameters of overlap syndrome that might be predictive of mortality. This study confirms troponin as possible predictor and adds elevated creatinine, BUN and reduced hemoglobin as possible early biomarkers in deceased patients. The analysis showed that reduced LVEF was not a seen in deceased patients.
Subject(s)
Myasthenia Gravis , Myocarditis , Myositis , Humans , Immune Checkpoint Inhibitors/adverse effects , Creatinine/adverse effects , Stroke Volume , Ventricular Function, Left , Myasthenia Gravis/chemically induced , Myasthenia Gravis/diagnosis , Myositis/chemically inducedABSTRACT
The rapid emergence of cardio-oncology has resulted in a rapid growth of cardio-oncology programs, dedicated professional societies sections and committees, and multiple collaborative networks that emerged to amplify the access to care in this new subspecialty. However, most existing data, position statements and guidelines are limited by the lack of availability of large clinical trials to support these recommendations. Furthermore, there are significant challenges regarding proper access to cardio-oncology care and treatment, particularly in marginalized and minority populations. The emergence and evolution of personalized medicine, artificial intelligence (AI), and machine learning in medicine and in cardio-oncology provides an opportunity for a more targeted, personalized approach to cardiovascular complications of cancer treatment. The proper implementation of these new modalities may facilitate a more equitable approach to adequate and universal access to cardio-oncology care, improve health related outcomes, and enable health care systems to eliminate the digital divide. This article reviews and analyzes the current status on these important issues.
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B-cell malignancies, most notably lymphomas, make up most of the non-Hodgkin lymphomas in the United States. There are limited randomized data comparing first- and second-generation Bruton tyrosine kinase (BTK) inhibitors. Our aim was to compare the safety profiles of first versus second-generation BTK inhibitors. A systematic search was performed from database inception to January 13, 2020. Studies with BTK inhibitor monotherapy for the treatment of B-cell malignancies in the adult population (>18 years old) were utilized and the adverse events (AEs) were extracted. Fifty-five studies that met the inclusion criteria were included in the systematic review with 41 studies with first generation and 14 studies with second generation. The review included both clinical trials and retrospective studies with average time of follow-up of 2 years for the first-generation group and 18 months for the second-generation group. We found that the incidence of cardiovascular AEs was significantly higher in the first-generation group (20.8%) as compared to the second-generation group (6.3%). However, there was a higher incidence of hematologic/oncologic and gastrointestinal side effects in the second-generation group compared to the first (62.3% compared to 39.2% and 36.9% compared to 28.9%). The number of Grade 5 cardiovascular events (death) was same in the first-generation group compared to the second generation. Further research is needed to develop highly selective BTK inhibitors to avoid unwanted AEs by minimizing off-targets.
Subject(s)
Neoplasms , Protein Kinase Inhibitors , Humans , Adolescent , Protein Kinase Inhibitors/adverse effects , Retrospective Studies , B-Lymphocytes , Neoplasms/drug therapyABSTRACT
BACKGROUND: The impact of pre-existing atrial fibrillation (AF) on outcomes after noncardiac surgery is not clear. OBJECTIVES: We aimed to study the impact of AF on the risk of adverse outcomes after noncardiac surgery in a nationwide cohort. METHODS: We identified Medicare beneficiaries admitted for noncardiac surgery from 2015 to 2019 and divided the study cohort into 2 groups: with and without AF. Noncardiac surgery was classified into vascular, thoracic, general, genitourinary, gynecological, orthopedics and neurosurgery, breast, head and neck, and transplant. We used propensity score matching on exact age, sex, race, urgency and type of surgery, revised cardiac risk index (RCRI) and CHA2DS2-VASc score, and tight caliper on other comorbidities. The study outcomes were 30-day mortality, stroke, myocardial infarction, and heart failure. We examined the incremental utility of AF in addition to RCRI to predict adverse events after noncardiac surgery. RESULTS: The study cohort included 8,635,758 patients who underwent noncardiac surgery (16.4% with AF). Patients with AF were older, more likely to be men, and had higher prevalence of comorbidities. After propensity score matching, AF was associated with higher risk of mortality (OR: 1.31; 95% CI: 1.30-1.32), heart failure (OR: 1.31; 95% CI: 1.30-1.33), and stroke (OR: 1.40; 95% CI: 1.37-1.43) and lower risk of myocardial infarction (OR: 0.81; 95% CI: 0.79-0.82). Results were consistent in subgroup analysis by sex, race, type of surgery, and all strata of RCRI and CHA2DS2-VASc score. AF improved the discriminative ability of RCRI (C-statistic 0.73 to 0.76). CONCLUSION: Pre-existing AF is independently associated with postoperative adverse outcomes after NCS.
Subject(s)
Atrial Fibrillation , Heart Failure , Myocardial Infarction , Stroke , Aged , Atrial Fibrillation/complications , Female , Humans , Male , Medicare , Myocardial Infarction/complications , Risk Assessment/methods , Risk Factors , Stroke/complications , Stroke/etiology , United States/epidemiologyABSTRACT
Introduction: Atrial fibrillation (AF) is associated with an increased risk of stroke. Despite evidence linking cancer and thrombosis, cancer is not part of the CHA2DS2VASc score. Hypothesis: Cancer is an independent risk factor for thromboembolic stroke in patients with AF. Method: The SEER database was utilized to identify patients with lung, colon, breast, and prostate cancers with AF and no prior diagnosis of stroke and. compared to controls within the dataset. The primary endpoint was rates of stroke per 100 person-years. Cox regression modeling and a nested model comparing CHA2DS2VASc score (Model 1) with a complete model including cancer diagnosis (Model 2) were performed. Models were compared using Akaike Information Criterion (AIC) and Net Reclassification Index (NRI). A propensity-matched cohort with equivalent CHA2DS2VASc scores determining stroke-free survival was also performed. Results: A total of 101,185 patients were included in the analysis, with 48,242 in the Cancer and 52,943 in the Non-cancer Group. Stroke rate per 100 person-years was significantly higher in the Cancer Group. The CHA2DS2VASc model (Model 1) was compared against a model including cancer (Model 2) showing improved predictability as assessed by both NRI and AIC. Cox regression analysis calculated a hazard ratio of 1.085 for Cancer, which was comparable to age >75, female sex, and diabetes. Propensity matched Kaplan-Meier curve demonstrated a decreased probability of stroke-free survival in the Cancer Group. Conclusion: Cancers increase the risk of stroke in patients with AF. Consideration should be given to the addition of cancer to the clinical scoring system.
Subject(s)
Amyloidosis/physiopathology , Atrial Fibrillation/drug therapy , Cardiomyopathies/physiopathology , Factor Xa Inhibitors/therapeutic use , Heart Failure/physiopathology , Stroke/prevention & control , Warfarin/therapeutic use , Aged , Aged, 80 and over , Amyloidosis/complications , Anticoagulants/therapeutic use , Antithrombins/therapeutic use , Atrial Fibrillation/complications , Cardiomyopathies/complications , Dabigatran/therapeutic use , Female , Heart Failure/complications , Humans , Male , Pyrazoles/therapeutic use , Pyridones/therapeutic use , Rivaroxaban/therapeutic use , Stroke/etiologyABSTRACT
BACKGROUND: Cardiovascular disease is a leading cause of death in general population and the second leading cause of mortality and morbidity in cancer survivors after recurrent malignancy in the United States. The growing awareness of cancer therapy-related cardiac dysfunction (CTRCD) has led to an emerging field of cardio-oncology; yet, there is limited knowledge on how to predict which patients will experience adverse cardiac outcomes. We aimed to perform unbiased cardiac risk stratification for cancer patients using our large-scale, institutional electronic medical records. METHODS AND FINDINGS: We built a large longitudinal (up to 22 years' follow-up from March 1997 to January 2019) cardio-oncology cohort having 4,632 cancer patients in Cleveland Clinic with 5 diagnosed cardiac outcomes: atrial fibrillation, coronary artery disease, heart failure, myocardial infarction, and stroke. The entire population includes 84% white Americans and 11% black Americans, and 59% females versus 41% males, with median age of 63 (interquartile range [IQR]: 54 to 71) years old. We utilized a topology-based K-means clustering approach for unbiased patient-patient network analyses of data from general demographics, echocardiogram (over 25,000), lab testing, and cardiac factors (cardiac). We performed hazard ratio (HR) and Kaplan-Meier analyses to identify clinically actionable variables. All confounding factors were adjusted by Cox regression models. We performed random-split and time-split training-test validation for our model. We identified 4 clinically relevant subgroups that are significantly correlated with incidence of cardiac outcomes and mortality. Among the 4 subgroups, subgroup I (n = 625) has the highest risk of de novo CTRCD (28%) with an HR of 3.05 (95% confidence interval (CI) 2.51 to 3.72). Patients in subgroup IV (n = 1,250) had the worst survival probability (HR 4.32, 95% CI 3.82 to 4.88). From longitudinal patient-patient network analyses, the patients in subgroup I had a higher percentage of de novo CTRCD and a worse mortality within 5 years after the initiation of cancer therapies compared to long-time exposure (6 to 20 years). Using clinical variable network analyses, we identified that serum levels of NT-proB-type Natriuretic Peptide (NT-proBNP) and Troponin T are significantly correlated with patient's mortality (NT-proBNP > 900 pg/mL versus NT-proBNP = 0 to 125 pg/mL, HR = 2.95, 95% CI 2.28 to 3.82, p < 0.001; Troponin T > 0.05 µg/L versus Troponin T ≤ 0.01 µg/L, HR = 2.08, 95% CI 1.83 to 2.34, p < 0.001). Study limitations include lack of independent cardio-oncology cohorts from different healthcare systems to evaluate the generalizability of the models. Meanwhile, the confounding factors, such as multiple medication usages, may influence the findings. CONCLUSIONS: In this study, we demonstrated that the patient-patient network clustering methodology is clinically intuitive, and it allows more rapid identification of cancer survivors that are at greater risk of cardiac dysfunction. We believed that this study holds great promise for identifying novel cardiac risk subgroups and clinically actionable variables for the development of precision cardio-oncology.
Subject(s)
Atrial Fibrillation/epidemiology , Coronary Artery Disease/epidemiology , Heart Failure/epidemiology , Myocardial Infarction/epidemiology , Neoplasms/complications , Risk Assessment , Stroke/epidemiology , Aged , Female , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Ohio/epidemiologyABSTRACT
The advent of immune checkpoint inhibitors (ICIs) has revolutionized the field of oncology, but these are associated with immune related adverse events. One such adverse event, is myocarditis, which has limited the continued immunosuppressive treatment options in patients afflicted by the disease. Pre-clinical and clinical data have found that specific ICI targets and precipitate distinct myocardial infiltrates, consistent with lymphocytic or giant cell myocarditis. Specifically, it has been reported that CTLA-4 inhibition preferentially results in giant cell myocarditis with a predominately CD4+ T cell infiltrate and PD-1 inhibition leads to lymphocytic myocarditis, with a predominately CD8+ T cell infiltrate. Our manuscript discusses the latest literature surrounding ICI pathways and targets, while detailing proposed mechanisms behind ICI mediated myocarditis.
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There have many major history-defining epidemics and pandemics in the 21st century. It is well known that acute infections can cause cardiovascular (CV) complications, especially in those with underlying cardiac disease. The variation in rates and types of CVD complications in major 21st century epidemics and pandemics varies greatly. The coronavirus disease 2019 (COVID-19) pandemic has caused the turmoil of the century and has COVID-19 has resulted in substantial human and economic loss. The novelty of COVID-19 and emerging CV effects is a new entity. In this review, we discuss the major epidemics and pandemics of the 21st century and associated CVD complications.