RESUMO
Recent reports have raised concerns about the association of chimeric antigen receptor T cell (CAR-T) with non-negligible cardiotoxicity, particularly atrial arrhythmias. First, we conducted a pharmacovigilance study to assess the reporting of atrial arrhythmias following CD19-directed CAR-T. Subsequently, to determine the incidence, risk factors and outcomes of atrial arrhythmias post-CAR-T, we compiled a retrospective single-centre cohort of non-Hodgkin lymphoma patients. Only commercial CAR-T products were considered. Atrial arrhythmias were nearly fourfold more likely to be reported after CAR-T therapy compared to all other cancer patients in the FAERS (adjusted ROR = 3.76 [95% CI 2.67-5.29]). Of the 236 patients in our institutional cohort, 23 (10%) developed atrial arrhythmias post-CAR-T, including 12 de novo arrhythmias, with most (83%) requiring medical intervention. Atrial arrhythmias frequently co-occurred with cytokine release syndrome and were associated with higher post-CAR-T infusion peak levels of IL-10, TNF-alpha and LDH, and lower trough levels of fibrinogen. In a multivariable analysis, risk factors for atrial arrhythmia were history of atrial arrhythmia (OR = 6.80 [2.39-19.6]) and using CAR-T product with a CD28-costimulatory domain (OR = 5.17 [1.72-18.6]). Atrial arrhythmias following CD19-CAR-T therapy are prevalent and associated with elevated inflammatory biomarkers, a history of atrial arrhythmia and the use of a CAR-T product with a CD28 costimulatory domain.
RESUMO
AIMS: Chimeric antigen receptor T-cell therapy (CAR-T) harnesses a patient's immune system to target cancer. There are sparse existing data characterizing death outcomes after CAR-T-related cardiotoxicity. This study examines the association between CAR-T-related severe cardiovascular events (SCE) and mortality. METHODS AND RESULTS: From a multi-centre registry of 202 patients receiving anti-CD19 CAR-T, covariates including standard baseline cardiovascular and cancer parameters and biomarkers were collected. Severe cardiovascular events were defined as a composite of heart failure, cardiogenic shock, or myocardial infarction. Thirty-three patients experienced SCE, and 108 patients died during a median follow-up of 297 (interquartile range 104-647) days. Those that did and did not die after CAR-T were similar in age, sex, and prior anthracycline use. Those who died had higher peak interleukin (IL)-6 and ferritin levels after CAR-T infusion, and those who experienced SCE had higher peak IL-6, C-reactive protein (CRP), ferritin, and troponin levels. The day-100 and 1-year Kaplan-Meier overall mortality estimates were 18% and 43%, respectively, while the non-relapse mortality (NRM) cumulative incidence rates were 3.5% and 6.7%, respectively. In a Cox model, SCE occurrence following CAR-T was independently associated with increased overall mortality risk [hazard ratio (HR) 2.8, 95% confidence interval (CI) 1.6-4.7] after adjusting for age, cancer type and burden, anthracycline use, cytokine release syndrome grade ≥ 2, pre-existing heart failure, hypertension, and African American ancestry; SCEs were independently associated with increased NRM (HR 3.5, 95% CI 1.4-8.8) after adjusting for cancer burden. CONCLUSION: Chimeric antigen receptor T-cell therapy recipients who experience SCE have higher overall mortality and NRM and higher peak levels of IL-6, CRP, ferritin, and troponin.
Assuntos
Insuficiência Cardíaca , Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/uso terapêutico , Interleucina-6 , Biomarcadores , Proteína C-Reativa , Troponina , Terapia Baseada em Transplante de Células e TecidosRESUMO
Importance: Anthracyclines treat a broad range of cancers. Basic and retrospective clinical data have suggested that use of atorvastatin may be associated with a reduction in cardiac dysfunction due to anthracycline use. Objective: To test whether atorvastatin is associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction. Design, Setting, and Participants: Double-blind randomized clinical trial conducted at 9 academic medical centers in the US and Canada among 300 patients with lymphoma who were scheduled to receive anthracycline-based chemotherapy. Enrollment occurred between January 25, 2017, and September 10, 2021, with final follow-up on October 10, 2022. Interventions: Participants were randomized to receive atorvastatin, 40 mg/d (n = 150), or placebo (n = 150) for 12 months. Main Outcomes and Measures: The primary outcome was the proportion of participants with an absolute decline in left ventricular ejection fraction (LVEF) of ≥10% from prior to chemotherapy to a final value of <55% over 12 months. A secondary outcome was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of <55% over 12 months. Results: Of the 300 participants randomized (mean age, 50 [SD, 17] years; 142 women [47%]), 286 (95%) completed the trial. Among the entire cohort, the baseline mean LVEF was 63% (SD, 4.6%) and the follow-up LVEF was 58% (SD, 5.7%). Study drug adherence was noted in 91% of participants. At 12-month follow-up, 46 (15%) had a decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55%. The incidence of the primary end point was 9% (13/150) in the atorvastatin group and 22% (33/150) in the placebo group (P = .002). The odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost 3 times greater for participants randomized to placebo compared with those randomized to atorvastatin (odds ratio, 2.9; 95% CI, 1.4-6.4). Compared with placebo, atorvastatin also reduced the incidence of the secondary end point (13% vs 29%; P = .001). There were 13 adjudicated heart failure events (4%) over 24 months of follow-up. There was no difference in the rates of incident heart failure between study groups (3% with atorvastatin, 6% with placebo; P = .26). The number of serious related adverse events was low and similar between groups. Conclusions and Relevance: Among patients with lymphoma treated with anthracycline-based chemotherapy, atorvastatin reduced the incidence of cardiac dysfunction. This finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use. Trial Registration: ClinicalTrials.gov Identifier: NCT02943590.
Assuntos
Antraciclinas , Antibióticos Antineoplásicos , Atorvastatina , Fármacos Cardiovasculares , Cardiopatias , Linfoma , Feminino , Humanos , Pessoa de Meia-Idade , Antraciclinas/efeitos adversos , Antraciclinas/uso terapêutico , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/uso terapêutico , Atorvastatina/uso terapêutico , Método Duplo-Cego , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/prevenção & controle , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda , Fármacos Cardiovasculares/uso terapêutico , Linfoma/tratamento farmacológico , Cardiopatias/induzido quimicamente , Cardiopatias/fisiopatologia , Cardiopatias/prevenção & controle , Seguimentos , Masculino , Adulto , IdosoRESUMO
AIMS: Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented. METHODS AND RESULTS: From an international registry of patients with ICI-associated myocarditis, clinical, CMR, and histopathological findings were collected. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. In 103 patients diagnosed with ICI-associated myocarditis who had a CMR, the mean left ventricular ejection fraction (LVEF) was 50%, and 61% of patients had an LVEF ≥50%. Late gadolinium enhancement (LGE) was present in 48% overall, 55% of the reduced EF, and 43% of the preserved EF cohort. Elevated T2-weighted short tau inversion recovery (STIR) was present in 28% overall, 30% of the reduced EF, and 26% of the preserved EF cohort. The presence of LGE increased from 21.6%, when CMR was performed within 4 days of admission to 72.0% when CMR was performed on Day 4 of admission or later. Fifty-six patients had cardiac pathology. Late gadolinium enhancement was present in 35% of patients with pathological fibrosis and elevated T2-weighted STIR signal was present in 26% with a lymphocytic infiltration. Forty-one patients (40%) had MACE over a follow-up time of 5 months. The presence of LGE, LGE pattern, or elevated T2-weighted STIR were not associated with MACE. CONCLUSION: These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis.
Assuntos
Inibidores de Checkpoint Imunológico , Miocardite , Meios de Contraste , Gadolínio , Humanos , Imagem Cinética por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Miocardite/induzido quimicamente , Valor Preditivo dos Testes , Volume Sistólico , Função Ventricular EsquerdaRESUMO
The Rohingya people of Myanmar (known as Burma before 1989) were stripped of citizenship in 1982, because they could not meet the requirement of proving their forefathers settled in Burma before 1823, and now account for one in seven of the global population of stateless people. Of the total 1·5 million Rohingya people living in Myanmar and across southeast Asia, only 82â000 have any legal protection obtained through UN-designated refugee status. Since 2012, more than 159â000 people, most of whom are Rohingya, have fled Myanmar in poorly constructed boats for journeys lasting several weeks to neighbouring nations, causing hundreds of deaths. We outline historical events preceding this complex emergency in health and human rights. The Rohingya people face a cycle of poor infant and child health, malnutrition, waterborne illness, and lack of obstetric care. In December, 2014, a UN resolution called for an end to the crisis. We discuss the Myanmar Government's ongoing treatment of Rohingya through the lens of international law, and the steps that the newly elected parliament must pursue for a durable solution.
Assuntos
Direitos Humanos , Grupos Minoritários , Saúde das Minorias , Identificação Social , Humanos , MianmarAssuntos
Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Miocardite/induzido quimicamente , Miocardite/diagnóstico , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/diagnóstico , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Sistema de Registros , Estudos RetrospectivosRESUMO
On Sept 29, 2013, the Framingham Heart Study will celebrate 65 years since the examination of the first volunteer in 1948. During this period, the study has provided substantial insight into the epidemiology and risk factors of cardiovascular disease. The origins of the study are closely linked to the cardiovascular health of President Franklin D Roosevelt and his premature death from hypertensive heart disease and stroke in 1945. In this Review we describe the events leading to the foundation of the Framingham Heart Study, and provide a brief historical overview of selected contributions from the study.
Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/história , Doenças Cardiovasculares/etiologia , Epidemiologia/história , História do Século XX , História do Século XXI , Humanos , Estudos Longitudinais , Massachusetts/epidemiologia , Apoio à Pesquisa como Assunto/história , Fatores de RiscoRESUMO
This review critically analyzes the incidence of trastuzumab-induced left ventricular systolic dysfunction and congestive heart failure (CHF), distinguishing between cases with and without prior anthracycline exposure. It highlights the fact that the elevated risk of trastuzumab-induced cardiotoxicity is closely associated with prior anthracycline exposure. In the absence of prior anthracycline exposure, the incidence rates of trastuzumab-induced cardiotoxicity, particularly CHF (ranging from 0% to 0.5%), are largely comparable with those reported in the general population, especially when reversibility is taken into account. Current cardiac surveillance recommendations during trastuzumab treatment have not yet adapted to the increasing adoption of nonanthracycline treatment strategies and the associated low risk of cardiotoxicity. We propose a refined monitoring protocol to reduce the frequency of cardiac evaluations for low-risk to moderate-risk patients, especially those receiving nonanthracycline treatments. By focusing on patients at high risk or those with prior anthracycline exposure, this strategy seeks to optimize the cost-effectiveness of cardiac care in oncology.
Assuntos
Cardiotoxicidade , Trastuzumab , Humanos , Trastuzumab/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Antraciclinas/efeitos adversos , Insuficiência Cardíaca/induzido quimicamenteRESUMO
Background: Cardiovascular events have been reported to occur in one in five patients receiving chimeric antigen receptor T-cell (CAR-T) therapy. Commonly reported effects including cardiomyopathy, heart failure, myocardial infarction (MI), and arrhythmia. Here, we present a novel case of a patient who developed acute ST segment elevations during CAR-T cell infusion. Case summary: A 76-year-old man with diffuse large B cell lymphoma was admitted for an investigational CD-19 directed, autologous CAR-T cell therapy. Less than 5â min into the CAR-T cell infusion, he developed severe chest pain, dyspnea, flushing, hypotension, and tachycardia. Electrocardiogram (EKG) showed inferior ST elevations and reciprocal lateral ST depressions. Emergent coronary angiography revealed mild non-obstructive coronary disease. ST segment changes and patient symptoms resolved after catheterization. Discussion: Given the complete resolution of symptoms and EKG abnormalities in the context of non-obstructive coronary artery disease, this clinical presentation was thought to be most consistent with ST elevation MI due to coronary vasospasm. The mechanism of this vasospasm is as yet not understood and may be related to an anaphylactic reaction or a cardiotoxicity related to the cell therapy agent. As the use of CAR-T therapy continues to expand, there is a need to further characterize the full spectrum of its cardiotoxic effects.
RESUMO
Many patients hospitalized for heart failure (HF) do not receive recommended follow-up cardiology care, and non-White patients are less likely to receive follow-up than White patients. Poor HF management may be particularly problematic in patients with cancer because cardiovascular co-morbidity can delay cancer treatments. Therefore, we sought to describe outpatient cardiology care patterns in patients with cancer hospitalized for HF and to determine if receipt of follow-up varied by race/ethnicity. SEER (Surveillance, Epidemiology, and End Results) data from 2007 to 2013 linked to Medicare claims from 2006 to 2014 were used. We included patients aged 66+ years with breast, prostate, or colorectal cancer, and preexisting HF. Patients with cancer were matched to patients in a noncancer cohort that included individuals with HF and no cancer. The primary outcome was receipt of an outpatient, face-to-face cardiologist visit within 30 days of HF hospitalization. We compared follow-up rates between cancer and noncancer cohorts, and stratified analyses by race/ethnicity. A total of 2,356 patients with cancer and 2,362 patients without cancer were included. Overall, 43% of patients with cancer and 42% of patients without cancer received cardiologist follow-up (p = 0.30). After multivariable adjustment, White patients were 15% more likely to receive cardiology follow-up than Black patients (95% confidence interval [CI] 1.02 to 1.30). Black patients with cancer were 41% (95% CI 1.11 to 1.78) and Asian patients with cancer were 66% (95% CI 1.11 to 2.49) more likely to visit a cardiologist than their noncancer counterparts. In conclusion, less than half of patients with cancer hospitalized for HF received recommended follow-up with a cardiologist, and significant race-related differences in cardiology follow-up exist. Future studies should investigate the reasons for these differences.
Assuntos
Cardiologia , Insuficiência Cardíaca , Neoplasias , Masculino , Humanos , Idoso , Estados Unidos/epidemiologia , Seguimentos , Medicare , Estudos Retrospectivos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Hospitalização , Neoplasias/complicações , Neoplasias/epidemiologiaRESUMO
PURPOSE: To determine the incidence and clinical predictors of intrathoracic complications in COVID-19 patients, and the association with outcomes. METHODS: In this retrospective cross-sectional study, we included 976 patients (age 61 ± 17 years, 62% male) who tested positive for SARS-CoV-2 between March 3-April 4, 2020 and underwent chest imaging. 3836 radiographs from 976 patients and 105 CTs from 88 patients were reviewed for intrathoracic complications, including pneumothorax, pneumomediastinum, pneumopericardium, lobar collapse, pleural effusion, and pneumatocele formation. RESULTS: There was a high rate of intrathoracic complications (197/976, 20%). Pleural effusion was the most common complication (168/976, 17%). Pneumothorax (30/976, 3%) and pneumatoceles (9/88, 10%) were also frequent. History of hypertension and high initial CXR severity score were independent risk factors for complications. Patients with any intrathoracic complication during admission had an over 11-fold risk of ICU admission (adjusted odds ratio [aOR] 11.2, p < 0.0001) and intubation (aOR 12.4, p < 0.0001), over 50% reduction in successful extubation (aOR 0.49, p = 0.02) and longer length of stay (median 13 versus 5 days, p < 0.0001). There was no difference in overall survival between patients with and without any complication (log-rank p = 0.94). CONCLUSION: In COVID-19 patients who underwent chest imaging, 1 in 5 patients have an intrathoracic complication, which are associated with higher level of care and prolonged hospital stay. Hypertension history and high CXR severity score confer an increased risk of complication. SUMMARY: Intrathoracic complications in COVID-19 are common and are predictive of ICU admission, need for intubation, less successful extubation, and longer length of stay but are not predictive of mortality.
Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Adulto , Idoso , COVID-19/complicações , COVID-19/epidemiologia , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2RESUMO
BACKGROUND: 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. OBJECTIVES: This study aimed to detail the role of GCS and GRS in ICI myocarditis. METHODS: 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. RESULTS: 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 30 days, 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). CONCLUSIONS: GCS and GRS are lower in ICI myocarditis, and the magnitude of reduction has prognostic significance.
Assuntos
Miocardite , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Miocardite/induzido quimicamente , Miocardite/diagnóstico por imagem , Miocardite/complicações , Volume Sistólico , Função Ventricular Esquerda , Inibidores de Checkpoint Imunológico , Estudos Retrospectivos , Valor Preditivo dos Testes , Troponina TRESUMO
Macrophage activation syndrome (MAS) is a disorder characterized by increased activation of mononuclear cells leading to phagocytosis of blood cell precursors in the bone marrow. We describe a case of MAS triggered by disseminated histoplasmosis occurring in a patient with Still's disease on long-term treatment with adalimumab.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/efeitos adversos , Histoplasmose/complicações , Síndrome de Ativação Macrofágica/etiologia , Doença de Still de Início Tardio/complicações , Doença de Still de Início Tardio/terapia , Adalimumab , Anticorpos Monoclonais Humanizados , Humanos , Fagocitose , Adulto JovemRESUMO
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: This study sought to investigate CPAEs associated with commercial CD19-directed CAR-T therapy. METHODS: In this retrospective, pharmacovigilance study, the authors used the Food and Drug Administration adverse event reporting system to identify CPAEs associated with axicabtagene-ciloleucel and tisagenlecleucel. The authors evaluated disproportionate reporting by the reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC025 >0 is deemed significant). Significant associations were further adjusted to age and sex (adj.ROR). RESULTS: The authors identified CAR-T reports of 2,657 patients, including 546 CPAEs (20.5%). CPAEs overlapped with cytokine release syndrome in 68.3% (373 of 546) of the reports. Compared with the full database, CAR-T was associated with overreporting 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 IC025 >0). Venous thromboembolic events (VTEs) were associated only with axicabtagene-ciloleucel therapy (n = 28 [1.6%], adj.ROR = 1.80 [1.24-2.62], IC025 >0). Atrial fibrillation (n = 55) was the leading tachyarrhythmia, followed by ventricular arrhythmias (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, the authors identified an association between CAR-T and various CPAEs, including tachyarrhythmias, cardiomyopathy, pericardial and pleural disorders, and VTEs. These findings should be considered in the multidisciplinary assessment for and monitoring of CAR-T therapy recipients.
Assuntos
Produtos Biológicos , Cardiotoxicidade , Doenças Cardiovasculares , Imunoterapia Adotiva , Pneumopatias , Receptores de Antígenos de Linfócitos T/administração & dosagem , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/classificação , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Monitoramento de Medicamentos/métodos , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/estatística & dados numéricos , Pneumopatias/induzido quimicamente , Pneumopatias/classificação , Pneumopatias/diagnóstico , Pneumopatias/prevenção & controle , Avaliação das Necessidades , Farmacovigilância , Estados Unidos , United States Food and Drug Administration/estatística & dados numéricosRESUMO
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 <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE. CONCLUSIONS: The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis.
Assuntos
Inibidores de Checkpoint Imunológico/efeitos adversos , Imageamento por Ressonância Magnética , Miocardite/induzido quimicamente , Miocardite/diagnóstico por imagem , Idoso , Técnicas de Imagem Cardíaca , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miocardite/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Myocarditis 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. METHODS: From 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. RESULTS: Both 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, p<0.001 and p=0.009, respectively). In contrast, the QTc interval at the time of myocarditis (435±39 ms) was not increased compared with pre-myocarditis baseline (422±27 ms, p=0.42). A prolonged QRS duration conferred an increased risk of subsequent MACE (HR 3.28, 95% CI 1.98 to 5.62, p<0.001). After adjustment, each 10 ms increase in the QRS duration conferred a 1.3-fold increase in the odds of MACE (95% CI 1.07 to 1.61, p=0.011). Conversely, there was no association between the QTc interval and MACE among men (HR 1.33, 95% CI 0.70 to 2.53, p=0.38) or women (HR 1.48, 95% CI 0.61 to 3.58, p=0.39). CONCLUSIONS: The 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.
Assuntos
Potenciais de Ação/efeitos dos fármacos , Eletrocardiografia , Sistema de Condução Cardíaco/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/efeitos adversos , Miocardite/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Miocardite/induzido quimicamente , Miocardite/fisiopatologia , Valor Preditivo dos Testes , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
CONTEXT.: Cardiac complications of immune checkpoint inhibitor therapy are rare, but reports of myocarditis are increasing. The findings have been described in case reports as lymphocytic myocarditis, but its histopathology is underreported. OBJECTIVE.: To review the histology of myocardial biopsy-proven cases of immune checkpoint-associated myocarditis and provide immunohistochemical characterization of the inflammatory infiltrate. DESIGN.: We have encountered 6 patients with biopsy-proven myocarditis in conjunction with therapy using anti-programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) agents with and without cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors and characterized the histopathology and immune cell profile. RESULTS.: The myocarditis was multifocal/diffuse and characterized by a predominant CD163-positive histiocytic infiltrate, with an associated CD8+ and PD-1+ T-lymphocytic infiltrate, some of which were granzyme B positive. Cardiac myocytes showed immunoreactivity for PD-L1 in areas of injury, confirmed using 2 different anti-PD-L1 clones. Four of 6 patients recovered from their cardiac injury. One patient had residual tachycardia-bradycardia syndrome and 1 patient expired. CONCLUSIONS.: The diffuse lymphohistiocytic myocarditis associated with this therapy is relatively distinctive, and this diagnosis is strongly suggested based on the histopathologic findings in the correct clinical setting.
Assuntos
Antineoplásicos/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Miocardite/diagnóstico , Neoplasias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Antígeno CTLA-4/metabolismo , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Masculino , Pessoa de Meia-Idade , Miocardite/induzido quimicamente , Miocardite/imunologia , Neoplasias/imunologia , Neoplasias/metabolismo , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismoRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) affects vulnerable populations (VP) adversely. PURPOSE: To evaluate overall imaging utilization in vulnerable subgroups (elderly, racial/ethnic minorities, socioeconomic status [SES] disadvantage) and determine if a particular subgroup has worse outcomes from COVID-19. MATERIALS/METHODS: Of 4110 patients who underwent COVID-19 testing from March 3-April 4, 2020 at NewYork-Presbyterian Hospital (NYP) health system, we included 1121 COVID-19 positive adults (mean age 59±18 years, 59% male) from two academic hospitals and evaluated imaging utilization rates and outcomes, including mortality. RESULTS: Of 897 (80%) VP, there were 465 (41%) elderly, 380 (34%) racial/ethnic minorities, and 479 (43%) SES disadvantage patients. Imaging was performed in 88% of patients and mostly portable/bedside studies, with 87% of patients receiving chest radiographs. There were 83% hospital admissions, 25% ICU admissions, 23% intubations, and 13% deaths. Elderly patients had greater imaging utilization, hospitalizations, ICU/intubation requirement, longer hospital stays, and >4-fold increase in mortality compared to non-elderlies (adjusted hazard ratio[aHR] 4.79, p<0.001). Self-reported minorities had fewer ICU admissions (p=0.03) and reduced hazard for mortality (aHR 0.53, p=0.004; complete case analysis: aHR 0.39, p<0.001 excluding "not reported"; sensitivity analysis: aHR 0.61, p=0.005 "not reported" classified as minorities) with similar imaging utilization, compared to non-minorities. SES disadvantage patients had similar imaging utilization and outcomes as compared to their counterparts. CONCLUSIONS: In a predominantly hospitalized New York City cohort, elderly patients are at highest mortality risk. Racial/ethnic minorities and SES disadvantage patients fare better or similarly to their counterparts, highlighting the critical role of access to inpatient medical care during the COVID-19 pandemic.
RESUMO
AIMS: The prognostic importance of post-diagnosis assessment of cardiorespiratory fitness (CRF) in cancer patients is not well established. We sought to examine the association between CRF and mortality in cancer patients. METHODS AND RESULTS: This was a single-centre cohort analysis of 1632 patients (58% male; 64 ± 12 years) with adult-onset cancer who were clinically referred for exercise treadmill testing a median of 7 [interquartile range (IQR): 3-12] years after primary diagnosis. Cardiorespiratory fitness was defined as peak metabolic equivalents (METs) achieved during standard Bruce protocol and categorized by tertiles. The association between CRF and all-cause and cause-specific mortality was assessed using multivariable Cox proportional hazard models adjusting for important covariates. Median follow-up was 4.6 (IQR: 2.6-7.0) years; a total of 411 deaths (229, 50, and 132 all-cause, cardiovascular (CV), and cancer related, respectively) occurred during this period. Compared with low CRF (range: 1.9-7.6 METs), the adjusted hazard ratio (HR) for all-cause mortality was 0.38 [95% confidence interval (CI): 0.28-0.52] for intermediate CRF (range: 7.7-10.6 METs) and 0.17 (95% CI: 0.11-0.27) for high CRF (range: 10.7-22.0 METs). The corresponding HRs were 0.40 (95% CI: 0.19-0.86) and 0.41 (95% CI: 0.16-1.05) for CV mortality and 0.40 (95% CI: 0.26-0.60) and 0.16 (95% CI: 0.09-0.28) for cancer mortality, respectively. The adjusted risk of all-cause, CV, and cancer mortality decreased by 26%, 14%, and 25%, respectively with each one MET increment in CRF. CONCLUSION: Cardiorespiratory fitness is a strong, independent predictor of all-cause, CV, and cancer mortality, even after adjustment for important clinical covariates in patients with certain cancers.
Assuntos
Aptidão Cardiorrespiratória , Neoplasias/mortalidade , Idoso , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/terapia , Causas de Morte/tendências , Teste de Esforço , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/diagnóstico , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: There is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving standard chemotherapy. There are no data on the use of GLS in ICI myocarditis. OBJECTIVES: This study sought to evaluate the role of GLS and assess its association with cardiac events among patients with ICI myocarditis. METHODS: This study retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI myocarditis (cases, n = 101) to that from patients receiving an ICI who did not develop myocarditis (control subjects, n = 92). Where available, GLS was also measured pre-ICI in both groups. Major adverse cardiac events (MACE) were defined as a composite of cardiogenic shock, arrest, complete heart block, and cardiac death. RESULTS: Cases and control subjects were similar in age, sex, and cancer type. At presentation with myocarditis, 61 cases (60%) had a normal ejection fraction (EF). Pre-ICI, GLS was similar between cases and control subjects (20.3 ± 2.6% vs. 20.6 ± 2.0%; p = 0.60). There was no change in GLS among control subjects on an ICI without myocarditis (pre-ICI vs. on ICI, 20.6 ± 2.0% vs. 20.5 ± 1.9%; p = 0.41); in contrast, among cases, GLS decreased to 14.1 ± 2.8% (p < 0.001). The GLS at presentation with myocarditis was lower among cases presenting with either a reduced (12.3 ± 2.7%) or preserved EF (15.3 ± 2.0%; p < 0.001). Over a median follow-up of 162 days, 51 (51%) experienced MACE. The risk of MACE was higher with a lower GLS among patients with either a reduced or preserved EF. After adjustment for EF, each percent reduction in GLS was associated with a 1.5-fold increase in MACE among patients with a reduced EF (hazard ratio: 1.5; 95% confidence interval: 1.2 to 1.8) and a 4.4-fold increase with a preserved EF (hazard ratio: 4.4; 95% confidence interval: 2.4 to 7.8). CONCLUSIONS: GLS decreases with ICI myocarditis and, compared with control subjects, was lower among cases presenting with either a preserved or reduced EF. Lower GLS was strongly associated with MACE in ICI myocarditis presenting with either a preserved or reduced EF.