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Cardiovascular and cancer outcomes intersect within the realm of cardio-oncology survivorship care, marked by disparities across ethnic, racial, social, and geographical landscapes. Although the clinical community is increasingly aware of this complex issue, effective solutions are trailing. To attain substantial public health impact, examinations of cancer types and cardiovascular risk mitigation require complementary approaches that elicit the patient's perspective, scale it to a population level, and focus on actionable population health interventions. Adopting such a multidisciplinary approach will deepen our understanding of patient awareness, motivation, health literacy, and community resources for addressing the unique challenges of cardio-oncology. Geospatial analysis aids in identifying key communities in need within both granular and broader contexts. In this review, we delineate a pathway that navigates barriers from individual to community levels. Data gleaned from these perspectives are critical in informing interventions that empower individuals within diverse communities and improve cardio-oncology survivorship.
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Background: Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI-myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this "cardiomyotoxicity" are lacking. Methods: A multicenter registry collected data retrospectively from 17 countries between 2014-2023. A multivariable cox regression model (hazard-ratio(HR), [95%confidence-interval]) was used to determine risk factors for the primary composite outcome: severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardio-muscular symptoms, diagnostics, and treatments. Time-dependent covariates were used and missing data were imputed. A point-based prognostic risk score was derived and externally validated. Results: In 748 patients (67% male, age 23-94), 30-days incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17% respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (HR=3.60[1.93-6.72]), presence of cardio-muscular symptoms (HR=2.60 [1.58-4.28]), low QRS-voltage on presenting electrocardiogram (HR for ≤0.5mV versus >1mV=2.08[1.31-3.30]), left ventricular ejection fraction (LVEF) <50% (HR=1.78[1.22-2.60]), and incremental troponin elevation (HR=1.86 [1.44-2.39], 2.99[1.91-4.65], 4.80[2.54-9.08], for 20, 200 and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-days primary outcome incidence increased gradually from 3.9%(risk-score=0) to 81.3%(risk-score≥4). This risk-score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low risk patients who were managed with no immunosuppression resulting in no cardio-myotoxic events. Conclusions: ICI-myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low-QRS voltage, depressed LVEF, and cardio-muscular symptoms. A risk-score incorporating these features performed well. Trial registration number: NCT04294771 and NCT05454527.
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Hematopoietic stem cell transplantation can cure various disorders but poses cardiovascular risks, especially for elderly patients and those with cardiovascular diseases. Cardiovascular evaluations are crucial in pretransplantation assessments, but guidelines are lacking. This American Heart Association scientific statement summarizes the data on transplantation-related complications and provides guidance for the cardiovascular management throughout transplantation. Hematopoietic stem cell transplantation consists of 4 phases: pretransplantation workup, conditioning therapy and infusion, immediate posttransplantation period, and long-term survivorship. Complications can occur during each phase, with long-term survivors facing increased risks for late effects such as cardiovascular disease, secondary malignancies, and endocrinopathies. In adults, arrhythmias such as atrial fibrillation and flutter are the most frequent acute cardiovascular complication. Acute heart failure has an incidence ranging from 0.4% to 2.2%. In pediatric patients, left ventricular systolic dysfunction and pericardial effusion are the most common cardiovascular complications. Factors influencing the incidence and risk of complications include pretransplantation therapies, transplantation type (autologous versus allogeneic), conditioning regimen, comorbid conditions, and patient age. The pretransplantation cardiovascular evaluation consists of 4 steps: (1) initial risk stratification, (2) exclusion of high-risk cardiovascular disease, (3) assessment of cardiac reserve, and (4) optimization of cardiovascular reserve. Clinical risk scores could be useful tools for the risk stratification of adult patients. Long-term cardiovascular management of hematopoietic stem cell transplantation survivors includes optimizing risk factors, monitoring, and maintaining a low threshold for evaluating cardiovascular causes of symptoms. Future research should prioritize refining risk stratification and creating evidence-based guidelines and strategies to optimize outcomes in this growing patient population.
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Doenças Cardiovasculares , Cardiopatias , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Criança , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/terapia , Sobrevivência , American Heart Association , Condicionamento Pré-Transplante/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Cardiopatias/etiologiaRESUMO
OBJECTIVES: The objective of this study was to determine the diagnostic performance of 15O-water positron emission tomography (PET) myocardial perfusion imaging to detect coronary artery disease (CAD) using the truth-standard of invasive coronary angiography (ICA) with fractional flow reserve (FFR) or instantaneous wave-Free Ratio (iFR) or coronary computed tomography angiogram (CCTA). BACKGROUND: 15O-water has a very high first-pass extraction that allows accurate quantification of myocardial blood flow and detection of flow-limiting CAD. However, the need for an on-site cyclotron and lack of automated production at the point of care and relatively complex image analysis protocol has limited its clinical use to date. METHODS: The RAPID WATER FLOW study is an open-label, multicenter, prospective investigation of the accuracy of 15O-water PET to detect obstructive angiographic and physiologically significant stenosis in patients with suspected CAD. The study will include the use of an automated system for producing, dosing, and injecting 15O-water and enrolling approximately 215 individuals with suspected CAD at approximately 10 study sites in North America and Europe. The primary endpoint of the study is the diagnostic sensitivity and specificity of the 15O-water PET study using the truth-standard of ICA with FFR or iFR to determine flow-limiting stenosis, or CCTA to rule out CAD and incorporating a quantitative analytic platform developed for the 15O-water PET acquisitions. Sensitivity and specificity are to be considered positive if the lower bound of the 95% confidence interval is superior to the threshold of 60% for both, consistent with prior registration studies. Subgroup analyses include assessments of diagnostic sensitivity, specificity, and accuracy in female, obese, and diabetic individuals, as well as in those with multivessel disease. All enrolled individuals will be followed for adverse and serious adverse events for up to 32 hours after the index PET scan. The study will have >90% power (one-sided test, α = 0.025) to test the hypothesis that sensitivity and specificity of 15O-water PET are both >60%. CONCLUSIONS: The RAPID WATER FLOW study is a prospective, multicenter study to determine the diagnostic sensitivity and specificity of 15O-water PET as compared to ICA with FFR/iFR or CCTA. This study will introduce several novel aspects to imaging registration studies, including a more relevant truth standard incorporating invasive physiologic indexes, coronary CTA to qualify normal individuals for eligibility, and a more quantitative approach to image analysis than has been done in prior pivotal studies. CLINICAL TRIAL REGISTRATION INFORMATION: Clinical-Trials.gov (#NCT05134012).
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Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Imagem de Perfusão do Miocárdio , Humanos , Feminino , Estudos Prospectivos , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Constrição Patológica , Água , Angiografia Coronária/métodos , Perfusão , Valor Preditivo dos Testes , Imagem de Perfusão do Miocárdio/métodos , Angiografia por Tomografia Computadorizada/métodosRESUMO
Quantitative PET attenuation correction (AC) for cardiac PET/CT and PET/MR is a challenging problem. We propose and evaluate an AC approach that uses coincidences from a relatively weak and physically fixed sparse external source, in combination with that from the patient, to reconstruct µ -maps based on physics principles alone. The low 30 cm3 volume of the source makes it easy to fill and place, and the method does not use prior image data or attenuation map assumptions. Our supplemental transmission aided maximum likelihood reconstruction of attenuation and activity (sTX-MLAA) algorithm contains an attenuation map update that maximizes the likelihood of terms representing coincidences originating from tracer in the patient and a weighted expression of counts segmented from the external source alone. Both external source and patient scatter and randoms are fully corrected. We evaluated performance of sTX-MLAA compared to reference standard CT-based AC with FDG PET/CT phantom studies; including modeling a patient with myocardial inflammation. Through an ROI analysis we measured ≤ 5 % bias in activity concentrations for PET images generated with sTX-MLAA and a TX source strength ≥ 12.7 MBq, relative to CT-AC. PET background variability (from noise and sparse sampling) was substantially reduced with sTX-MLAA compared to using counts segmented from the transmission source alone for AC. Results suggest that sTX-MLAA will enable quantitative PET during cardiac PET/CT and PET/MR of human patients.
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Imagem Multimodal , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Imagem Multimodal/métodos , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Algoritmos , Processamento de Imagem Assistida por Computador/métodosRESUMO
Preclinical data strongly suggest that myocardial steatosis leads to adverse cardiac remodelling and left ventricular dysfunction. Using 1 H cardiac magnetic resonance spectroscopy, similar observations have been made across the spectrum of health and disease. The purpose of this brief review is to summarize these recent observations. We provide a brief overview of the determinants of myocardial triglyceride accumulation, summarize the current evidence that myocardial steatosis contributes to cardiac dysfunction, and identify opportunities for further research.
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Cardiopatias , Disfunção Ventricular Esquerda , Humanos , Miocárdio/patologia , Coração , Espectroscopia de Ressonância Magnética , Disfunção Ventricular Esquerda/patologia , Triglicerídeos , Função Ventricular EsquerdaRESUMO
Interest in ketones as a cardiac "super fuel" has grown significantly following reports of a marked increase in cardiac output after exogenous ketone administration in heart failure. However, the extent to which this increase in cardiac output is related to changes in cardiac contractility, and dependent on the presence of heart failure, remains incompletely understood. Therefore, we performed a randomized, double-blind, placebo-controlled study of oral ketone ester in young healthy volunteers. Baseline cardiac magnetic resonance imaging was performed and repeated every 15 min for 60 min after ketone and placebo ingestion to assess changes in left ventricular function. As expected, circulating ß-hydroxybutyrate increased rapidly after ketone ingestion, but did not change with placebo (interaction: P < 0.001). Consistent with prior investigations, ketone ingestion resulted in an average 1 L/min increase in cardiac output after 60 min that did not occur with placebo (interaction: P = 0.026). This increase in cardiac output was primarily driven by an increase in heart rate after ketone ingestion (interaction: P = 0.018), with only a modest increase in stroke volume (interaction: P = 0.037). Changes in left ventricular strain and twist mechanics were limited. Taken together, the increase in cardiac output following an acute elevation in circulating ß-hydroxybutyrate is primarily driven by changes in cardiac chronotropy, with minimal inotropic contribution.NEW & NOTEWORTHY In this randomized, double-blind, placebo-controlled study of oral ketone ester in young healthy volunteers, we show a marked increase in cardiac output (â¼1 L/min), driven primarily by changes in chronotropy. The cardiac magnetic resonance imaging data support the limited role for inotropy.
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Insuficiência Cardíaca , Função Ventricular Esquerda , Adulto , Humanos , Função Ventricular Esquerda/fisiologia , Ácido 3-Hidroxibutírico/farmacologia , Contração Miocárdica/fisiologia , ÉsteresRESUMO
Advances in cancer therapeutics have led to dramatic improvements in survival, now inclusive of nearly 20 million patients and rising. However, cardiovascular toxicities associated with specific cancer therapeutics adversely affect the outcomes of patients with cancer. Advances in cardiovascular imaging have solidified the critical role for robust methods for detecting, monitoring, and prognosticating cardiac risk among patients with cancer. However, decentralized evaluations have led to a lack of consensus on the optimal uses of imaging in contemporary cancer treatment (eg, immunotherapy, targeted, or biological therapy) settings. Similarly, available isolated preclinical and clinical studies have provided incomplete insights into the effectiveness of multiple modalities for cardiovascular imaging in cancer care. The aims of this scientific statement are to define the current state of evidence for cardiovascular imaging in the cancer treatment and survivorship settings and to propose novel methodological approaches to inform the optimal application of cardiovascular imaging in future clinical trials and registries. We also propose an evidence-based integrated approach to the use of cardiovascular imaging in routine clinical settings. This scientific statement summarizes and clarifies available evidence while providing guidance on the optimal uses of multimodality cardiovascular imaging in the era of emerging anticancer therapies.
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Doenças Cardiovasculares , Neoplasias , Estados Unidos , Humanos , American Heart Association , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Oncologia , Imagem Multimodal/métodos , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/terapiaRESUMO
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.
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Neoplasias da Mama , Cardiologistas , Cardiologia , Neoplasias , Humanos , Feminino , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/terapia , Oncologia , Sistema de Registros , Estudos Multicêntricos como AssuntoRESUMO
Mounting evidence suggests that myocardial steatosis contributes to left ventricular diastolic dysfunction, but definitive evidence in humans is lacking due to confounding comorbidities. As such, we utilized a 48-h food restriction model to acutely increase myocardial triglyceride (mTG) content - measured by 1 H magnetic resonance spectroscopy - in 27 young healthy volunteers (13 men/14 women). Forty-eight hours of fasting caused a more than 3-fold increase in mTG content (P < 0.001). Diastolic function - defined as early diastolic circumferential strain rate (CSRd) - was unchanged following the 48-h fasting intervention, but systolic circumferential strain rate was elevated (P < 0.001), indicative of systolic-diastolic uncoupling. Indeed, in a separate control experiment in 10 individuals, administration of low-dose dobutamine (2 µg/kg/min) caused a similar change in systolic circumferential strain rate as was found during 48 h of food restriction, along with a proportionate increase in CSRd, such that the two metrics remained coupled. Taken together, these data indicate that myocardial steatosis contributes to diastolic dysfunction by impairing diastolic-systolic coupling in healthy adults, and suggest that steatosis may contribute to the progression of heart disease. KEY POINTS: Preclinical evidence strongly suggests that myocardial lipid accumulation (termed steatosis) is an important mechanism driving heart disease. Definitive evidence in humans is limited due to the confounding influence of multiple underlying comorbidities. Using a 48-h food restriction model to acutely increase myocardial triglyceride content in young healthy volunteers, we demonstrate an association between myocardial steatosis and left ventricular diastolic dysfunction. These data advance the hypothesis that myocardial steatosis may contribute to diastolic dysfunction and suggest myocardial steatosis as a putative therapeutic target.
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Cardiomiopatias , Disfunção Ventricular Esquerda , Masculino , Adulto , Humanos , Feminino , Função Ventricular Esquerda , Diástole , Miocárdio , TriglicerídeosRESUMO
Objective: The primary objectives of this pilot study were to assess cognition and cerebral metabolic rate of oxygen (CMRO2) consumption in people with severe obesity before (baseline), and again, 2- and 14-weeks after sleeve gastrectomy bariatric surgery. Methods: Six people with severe/class 3 obesity (52 ± 10 years, five females, body mass index (BMI) = 41.9 ± 3.9 kg/m2), and 10 normal weight sex- and age-matched healthy controls (HC) (48 ± 6 years, eight females, 22.8 ± 1.9 kg/m2). Global CMRO2 was measured non-invasively using MRI and cognition using the Integneuro testing battery. Results: Following a sleeve gastrectomy induced weight loss of 6.4 ± 2.5 kg (% total-body-weight-lost = 5.4) over two-weeks, cognition total scores improved by 0.8 ± 0.5 T-scores (p=0.03, 15.8% improvement from baseline). Weight loss over 14-weeks post-surgery was 15.4 ± 3.6 kg (% total-body-weight-lost = 13.0%) and cognition improved by 1.1 ± 0.4 (p=0.003, 20.6% improvement from baseline). At 14-weeks, cognition was 6.4 ± 0.7, comparable to 6.0 ± 0.6 observed in the HC group. Baseline CMRO2 was significantly higher compared to the HC (230.4 ± 32.9 vs. 177.9 ± 33.9 µmol O2/100 g/min, p=0.02). Compared to baseline, CMRO2 was 234.3 ± 16.2 µmol O2/100 g/min at 2-weeks after surgery (p=0.8, 1.7% higher) and 217.3 ± 50.4 at 14-weeks (p=0.5, 5.7% lower) after surgery. 14-weeks following surgery, CMRO2 was similar to HC (p=0.17). Conclusion: Sleeve gastrectomy induced weight loss was associated with an increase in cognition and a decrease in CMRO2 observed 14-weeks after surgery. The association between weight loss, improved cognition and CMRO2 decrease should be evaluated in larger future studies.
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Cirurgia Bariátrica , Oxigênio , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Projetos Piloto , Encéfalo , Obesidade , Cognição , Redução de PesoRESUMO
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.
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Antineoplásicos , Doenças Cardiovasculares , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Cardiopatias , Neoplasias , Antineoplásicos/efeitos adversos , Inteligência Artificial , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/diagnóstico por imagem , Cardiopatias/diagnóstico , Humanos , Oncologia , Neoplasias/complicações , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológicoRESUMO
Chimeric antigen receptor T-cell (CAR T) therapy is a revolutionary personalized therapy that has significantly impacted the treatment of patients with hematologic malignancies refractory to other therapies. Cytokine release syndrome (CRS) is a major side effect of CAR T therapy that can occur in 70-90% of patients, with roughly 40% of patients at grade 2 or higher. CRS can cause an intense inflammatory state leading to cardiovascular complications, including troponin elevation, arrhythmias, hemodynamic instability, and depressed left ventricular systolic function. There are currently no standardized guidelines for the management of cardiovascular complications due to CAR T therapy, but systematic practice patterns are emerging. In this review, we contextualize the history and indications of CAR T cell therapy, side effects related to this treatment, strategies to optimize the cardiovascular health prior to CAR T and the management of cardiovascular complications related to CRS. We analyze the existing data and discuss potential future approaches.
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Gender differences exist throughout the medical field and significant progress has been made in understanding the effects of gender in many aspects of healthcare. The field of cardio-oncology is diverse and dynamic with new oncologic and cardiovascular therapies approved each year; however, there is limited knowledge regarding the effects of gender within cardio-oncology, particularly the impact of gender on cardiotoxicities. The relationship between gender and cardio-oncology is unique in that gender likely affects not only the biological underpinnings of cancer susceptibility, but also the response to both oncologic and cardiovascular therapies. Furthermore, gender has significant socioeconomic and psychosocial implications which may impact cancer and cardiovascular risk factor profiles, cancer susceptibility, and the delivery of healthcare. In this review, we summarize the effects of gender on susceptibility of cancer, response to cardiovascular and cancer therapies, delivery of healthcare, and highlight the need for further gender specific studies regarding the cardiovascular effects of current and future oncological treatments.
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PURPOSE: Immune checkpoint blocker (ICB) associated myocarditis (ICB-myocarditis) may present similarly and/or overlap with other cardiac pathology including acute coronary syndrome presenting a challenge for prompt clinical diagnosis. METHODS: An international registry was used to retrospectively identify cases of ICB-myocarditis. Presence of coronary artery disease (CAD) was defined as coronary artery stenosis >70% in patients undergoing coronary angiogram. RESULTS: Among 261 patients with clinically suspected ICB-myocarditis who underwent a coronary angiography, CAD was present in 59/261 patients (22.6%). Coronary revascularization was performed during the index hospitalisation in 19/59 (32.2%) patients. Patients undergoing coronary revascularization less frequently received steroids administration within 24 h of admission compared to the other groups (p = 0.029). Myocarditis-related 90-day mortality was 9/17 (52.7%) in the revascularised cohort, compared to 5/31 (16.1%) in those not revascularized and 25/156 (16.0%) in those without CAD (p = 0.001). Immune-related adverse event-related 90-day mortality was 9/17 (52.7%) in the revascularized cohort, compared to 6/31 (19.4%) in those not revascularized and 31/156 (19.9%) in no CAD groups (p = 0.007). All-cause 90-day mortality was 11/17 (64.7%) in the revascularized cohort, compared to 13/31 (41.9%) in no revascularization and 60/158 (38.0%) in no CAD groups (p = 0.10). After adjustment of age and sex, coronary revascularization remained associated with ICB-myocarditis-related death at 90 days (hazard ratio [HR] = 4.03, 95% confidence interval [CI] 1.84-8.84, p < 0.001) and was marginally associated with all-cause death (HR = 1.88, 95% CI, 0.98-3.61, p = 0.057). CONCLUSION: CAD may exist concomitantly with ICB-myocarditis and may portend a poorer outcome when revascularization is performed. This is potentially mediated through delayed diagnosis and treatment or more severe presentation of ICB-myocarditis.