Cardiovascular Magnetic Resonance Imaging in Patients With Ibrutinib-Associated Cardiotoxicity.

Importance: Ibrutinib has been associated with serious cardiotoxic arrhythmias. In preclinical models, these events are paralleled or proceeded by diffuse myocardial injury (inflammation and fibrosis). Yet whether this is seen in patients or has implications for future cardiotoxic risk is unknown. Objective: To assess the incidence and outcomes of myocardial injury among patients with ibrutinib-related cardiotoxicity. Design, Setting, and Participants: This cohort study included consecutive patients treated with ibrutinib from 2012 to 2019, phenotyped using cardiovascular magnetic resonance (CMR) from a large US Comprehensive Cancer Center registry. Exposures: Ibrutinib treatment for cancer control. Main Outcomes and Measures: The primary outcome was the presence of late gadolinium enhancement (LGE) fibrosis. The secondary outcome was the occurrence of major adverse cardiac events (MACE), defined as atrial fibrillation, heart failure, symptomatic ventricular arrhythmias, and sudden death of probable or definite ibrutinib association after CMR. We also assessed parametric-mapping subclinical fibrosis (native-T1, extracellular volume fraction) and inflammation/edema (max-T2) measures. Cardiovascular magnetic resonance measures were compared with those obtained in similar consecutive patients with cancer without ibrutinib treatment (pretreatment controls). Observed measures were also compared with similar-aged broad population rates (general-population controls) and a broader pool of cardiovascular disease (CVD) risk-matched cancer controls. Multivariable regression was used to assess the association between CMR measures and MACE. Results: Overall, 49 patients treated with ibrutinib were identified, including 33 imaged after treatment initiation (mean [SD] age, 65 [10] years, 9 [27%] with hypertension, and 23 [69.7%] with index-arrhythmias); median duration of ibrutinib-use was 14 months. The mean (SD) pretreatment native T1 was 977.0 (73.0) ms, max-T2 56.5 (4.0) ms, and 4 (13.3%) had LGE. Posttreatment initiation, mean (SD) native T1 was 1033.7 (48.2) ms, max-T2 61.5 (4.8) ms, and 17 (54.8%) had LGE (P < .001, P = .01, and P < .001, respectively, pre- vs post-ibrutinib treatment). Native T12SDs was elevated in 9 (28.6%), and max-T22SDs in 21 (63.0%), respectively. Cardiovascular magnetic resonance measures were highest in those with suspected toxic effects (P = .01 and P = .01, respectively). There was no association between traditional CVD-risk or cancer-treatment status and abnormal CMR measures. Among those without traditional CVD, 16 (58.6%) had LGE vs 38 (13.3%) in matched-controls (relative-risk, 4.8; P < .001). Over a median follow-up of 19 months, 13 (39.4%) experienced MACE. In multivariable models inclusive of traditional CVD risk factors, LGE (hazard ratio [HR], 4.9; P = .04), and native-T12SDs (HR, 3.3; P = .05) associated with higher risks of MACE. Conclusions and Relevance: In this cohort study, myocardial injury was common in ibrutinib users, and its presence was associated with higher cardiotoxic risk.

Hypertensive events after the initiation of contemporary cancer therapies for breast cancer control.

BACKGROUND: Contemporary therapies improve breast cancer (BC) outcomes. Yet, many of these therapies have been increasingly linked with serious cardiotoxicity, including reports of profound hypertension. Yet, the incidence, predictors, and impacts of these events are largely unknown. METHODS: Leveraging two large U.S.-based registries, the National Inpatient Sample (NIS) and the Food and Drug Administration Adverse Event Reporting System (FAERS) databases, we assessed the incidence, factors, and outcomes of hypertensive events among BC patients from 2007 to 2015. Differences in baseline characteristics, hypertension-related discharges, and complications were examined over time. Further, we performed a disproportionality analysis using reporting-odds-ratios (ROR) to determine the association between individual BC drugs and hypertensive events. Utilizing an ROR cutoff of >1.0, we quantified associations by drug-class, and individual drugs with the likelihood of excess hypertension. RESULTS: Overall, there were 5,464,401 BC-admissions, of which 46,989 (0.8%) presented with hypertension. Hypertensive BC patients were older, and saw initially increased in-hospital mortality, which equilibrated over time. The mean incidence of hypertension-related admissions was 732 per 100,000 among BC patients, versus 96 per 100,000 among non-cancer patients (RR 7.71, p < 0.001). Moreover, in FAERS, those with hypertension versus other BC-treatment side-effects were more frequently hospitalized (40.1% vs. 36.7%, p < 0.001), and were most commonly associated with chemotherapy (45.9%). Outside of Eribulin (ROR 3.36; 95% CI 1.37-8.22), no specific drug was associated with a higher reporting of hypertension; however, collectively BC drugs were associated with a higher odds of hypertension (ROR 1.66; 95% CI 1.09-2.53). CONCLUSIONS: BC therapies are associated with a substantial increase in limiting hypertension.

Incidence of pacing-induced cardiomyopathy in pacemaker-dependent patients is lower with leadless pacemakers compared to transvenous pacemakers.

INTRODUCTION: Frequent right AQ4ventricular pacing (≥40%) with a transvenous pacemaker (TVP) is associated with the risk of pacing-induced cardiomyopathy (PICM). Leadless pacemakers (LPs) have distinct physical and mechanical differences from TVP. The risk of PICM with LP is not known. To identify incidence, predictors, and long-term outcomes of PICM in LP and TVP patients. METHODS: The study comprised all pacemaker-dependent patients with LP or TVP who had left ventricular ejection fraction (LVEF) of ≥50 from 2014 to 2019. The incidence of PICM (≥10% LVEF drop) was assessed with an echocardiogram. Predictors for PICM were identified using multivariate analysis. Long-term outcomes after cardiac resynchronization (CRT) were assessed in both groups. RESULTS: A total of 131 patients with TVP and 67 with LP comprised the study. All patients in the TVP group and the majority in the LP group underwent atrioventricular node ablation. The mean follow-up duration in TVP and LP groups was 592 ± 549 and 817 ± 600 days, respectively. A total of 18 (13.7%) patients in TVP and 2 (3%) in LP developed PICM after a median duration of 254 (interquartile range: 470) days. The incidence of PICM was significantly higher with TVP compared with LP (p = .02). TVP as pacing modality was a positive (odds ratio [OR]: 1.07) while age was negative (OR: 0.94) predictor for PICM on multivariable analysis. Both patients in LP and all except two in the TVP group responded to CRT. CONCLUSION: Incidence of PICM is significantly lower with LP compared with TVP in pacemaker-dependent patients. Age and TVP as pacing modality were predictors for PICM.

Contemporary Understandings of Cardiovascular Disease After Cancer Radiotherapy: a Focus on Ischemic Heart Disease.

PURPOSE OF REVIEW: Radiation-induced cardiovascular disease, including coronary artery disease, is a well-known sequela of radiation therapy and represents a significant source of morbidity and mortality for cancer survivors. This review examines current literature and guidelines to care for this growing population of cancer survivors. RECENT FINDINGS: The development of radiation-induced ischemic heart disease following radiation can lead even to early cardiotoxicities, inclusive of coronary artery disease, which limit cancer treatment outcomes. These coronary lesions tend to be diffuse, complex, and proximal. Early detection with multimodality imaging and targeted intervention is required to minimize these risks. Early awareness, detection, and management of radiation-induced cardiovascular disease are paramount as cancer survivorship continues to grow.

Current Perspectives on Coronavirus Disease 2019 and Cardiovascular Disease: A White Paper by the JAHA Editors.

Coronavirus Disease 2019 (COVID-19) has infected more than 3.0 million people worldwide and killed more than 200,000 as of April 27, 2020. In this White Paper, we address the cardiovascular co-morbidities of COVID-19 infection; the diagnosis and treatment of standard cardiovascular conditions during the pandemic; and the diagnosis and treatment of the cardiovascular consequences of COVID-19 infection. In addition, we will also address various issues related to the safety of healthcare workers and the ethical issues related to patient care in this pandemic.

A Tri-Institutional Approach to Address Disparities in Children's Oncology Group Clinical Trial Accrual for Adolescents and Young Adults and Underrepresented Minorities.

Purpose: Enrollment in Children's Oncology Group (COG) clinical trials has led to significant improvements in survival; however, disparities in survival persist, particularly among ethnic minorities, adolescents and young adults (AYAs), and the underinsured, partly due to inadequate access to cooperative group cancer clinical trials. In 2008, two COG sites University of Illinois at Chicago (UIC) and Rush University Medical Center, and a nonmember institution, John H Stroger Hospital, created a unified COG program utilizing one lead Institutional Review Board and research team. This study assesses the impact that the tri-institutional COG program had on clinical trial accrual for minority, AYA, and uninsured patients. Methods: Analysis and comparison of COG enrollment data from 2002 to 2008 (pre-merger) and 2008 to 2017 (post-merger) by age, ethnicity, insurance type, clinical trial type, oncologic diagnosis, and specialty of the enrolling physician were completed. Results: Following the merger, the total studies open to enrollment increased by 100%, enrollments increased by 446%, and, for each diagnoses, increased by more than 200%. Enrollment of ethnic minorities rose by 533%, most significantly for Hispanic patients by 925%. AYA enrollments increased by 822%. There was a 28-fold increase in enrollment of uninsured patients. Significantly more providers from various oncology specialties were engaged in enrolling patients and a consistent increase in the percentile standing of the program occurred after the merger. Conclusions: Creation of a tri-institutional COG research program was associated with significant increases in clinical trial enrollments, especially for underrepresented minorities, AYAs, and uninsured patients. The UIC/Rush/Stroger COG Program provides a novel and exemplary approach to address cancer health disparities for these vulnerable populations.

Homocistinuria clásica. Presentación de 1 caso / Classic homocystinuria. A case report

Se presentó un paciente joven masculino que ingresó en el Centro Internacional de Restauración Neurológica por retraso mental ligero y epilepsia. Se evaluó minuciosamente y se encontró además, un hábito marfanoide caracterizado por dolicostenomelia, aracnodactilia, pectus carinatum, escápula alada y pie plano bilateral. Se consideró como probables diagnósticos, el síndrome de Marfán, el de X frágil y la homocistinuria clásica. Los dos primeros se excluyeron de acuerdo con los datos clínicos y el resultado de los estudios complementarios. Se concluyó como una homocistinuria clásica, teniendo en cuenta la asociación de retraso mental ligero, epilepsia, osteoporosis y hábito marfanoide. Finalmente, el diagnóstico estuvo apoyado por la prueba de cianuro-nitroprusiato en orina que resultó positiva. Se hizo una breve revisión de la base patogénica de la enfermedad

Homocistinuria clásica: presentación de 1 caso / Classic homocystinuria: a case report

Se presentó un paciente joven masculino que ingresó en el Centro Internacional de Restauración Neurológica por retraso mental ligero y epilepsia. Se evaluó minuciosamente y se encontró además, un hábito marfanoide caracterizado por dolicostenomelia, aracnodactilia, pectus carinatum, escápula alada y pie plano bilateral. Se consideró como probables diagnósticos, el síndrome de Marfán, el de X frágil y la homocistinuria clásica. Los dos primeros se excluyeron de acuerdo con los datos clínicos y el resultado de los estudios complementarios. Se concluyó como una homocistinuria clásica, teniendo en cuenta la asociación de retraso mental ligero, epilepsia, osteoporosis y hábito marfanoide. Finalmente, el diagnóstico estuvo apoyado por la prueba de cianuro-nitroprusiato en orina que resultó positiva. Se hizo una breve revisión de la base patogénica de la enfermedad(AU)

Neuromodulación farmacológica en la enfermedad cerebrovascular / Pharmacological neuromodulation in cerebrovascular disease

La enfermedad cerebrovascular representa la tercera causa de muerte en los países desarrollados y en vías de desarrollo y sus secuelas se comportan como la primera causa de invalidez en los adultos. Las orientaciones terapéuticas más importantes en estos pacientes consisten en mejorar el flujo sanguíneo cerebral y reducir o bloquear las consecuencias metabólicas a nivel subcelular y celular. Los importantes avances producidos en los últimos años en el conocimiento de los mecanismos fisiopatológicos de la isquemia cerebral y en el desarrollo de nuevos fármacos han planteado las expectativas reales de tratamiento y el rechazo de actitudes nihilistas. Se hizo una breve revisión del concepto de plasticidad neuronal y neuromodulación farmacológica. Se expuso un grupo de fármacos neuroprotectores y neurotróficos, algunos de forma experimental, usados en la enfermedad cerebrovascular aguda y crónica

Neuromodulación farmacológica en la enfermedad cerebrovascular / Pharmacological neuromodulation in cerebrovascular disease

La enfermedad cerebrovascular representa la tercera causa de muerte en los países desarrollados y en vías de desarrollo y sus secuelas se comportan como la primera causa de invalidez en los adultos. Las orientaciones terapéuticas más importantes en estos pacientes consisten en mejorar el flujo sanguíneo cerebral y reducir o bloquear las consecuencias metabólicas a nivel subcelular y celular. Los importantes avances producidos en los últimos años en el conocimiento de los mecanismos fisiopatológicos de la isquemia cerebral y en el desarrollo de nuevos fármacos han planteado las expectativas reales de tratamiento y el rechazo de actitudes nihilistas. Se hizo una breve revisión del concepto de plasticidad neuronal y neuromodulación farmacológica. Se expuso un grupo de fármacos neuroprotectores y neurotróficos, algunos de forma experimental, usados en la enfermedad cerebrovascular aguda y crónica(AU)

Módulo I: análisis de vulnerabilidad e identificación de medidas de mitigación / Module 1: vulnerability and analisys and identification of mitigation measures

El documento presenta una investigación de la vulnerabilidad e identificación de medidas de mitigación en la Cuenca del río Juan Díaz. A lo largo del análisis, se van definiendo los conceptos de Riesgo, Amenaza y Vulnerabilidad; Describe los aspectos geológicos que caracterizan la Cuenca del río Juan Díaz; Define los aspectos sociales y demográficos del distrito de Panamá; Analiza la vulnerabilidad ante los casos de inundaciones; y establece las medidas de mitigación a tomar

Financiamiento de la atención a la salud de la población de la tercera edad / Health care financing for the elderly

Determinar el financiamento directo de la atención a la salud de los adultos mayores en México y hacer una estimación de los gastos que este servicio implica. Material y métodos. Se estimaron las necesidadesde atención a la salud de los ancianos con base en estadísticas censales y en la Encuesta Nacional de Salud II. Enseguida se estimaron las tendencias en el uso de servicios entre los adulto mayores, de acuerdo con la información emitida por distintas instituciones del sector salud. Finalmente, después de haber analizado la aplicación de distintos modelos de atención a la salud en los ancianos en otros países y de haber proyectado las futuras demandas al respecto en México, se estimó el gasto mediante dos métodos: a) con base en una fórmula que incluye egresos, costo día/cama y días de estancia, y b) calculando el gasto de hospitalización y consulta a partir del número de egresos. Resultados. La necesidad actual de atención del adulto mayor supera la capacidad del sistema de salud para proveer los servicios adecuados. De acuerdo con el segundo método de estimación, en 1994 se gastó 4.9 por ciento del presupuesto del sector público en la atención hospitalaria para la población de más de 60 años. Conclusiones. En México, los adultos mayores se han convertido en una prioridad por la naturaleza de sus necesidades y demandas; su atención es una de las fuentes de costos más importantes en los servicios hospitalarios. Es necesario, por tanto, desarrollar una agenda de investigación que permita programar, planear y presupuestar el gasto en asistencia médica para el anciano

Objetive. To determine the direct financial requirements for providing health care to the elderly in Mexico along with an estimation of the current expenditures from services provided to this same population. Material and methods. Health care needs for the elderly were estimated from the censuses and the database of the National Health Survey II. In addition, service use trends for the aged were obtained from health sector statistical yearbooks. Finally, the amounts of expenditures were estimated by two methods: a) using a formula that considers hospital discharges, daily bed costs and length of stay; and b) inferring hospital expenditures and ambulatory visits from the numbers of hospital discharges. Results. Currently health care needs of the aged outnumber the amount of resources and the capacity of the health care sector to meet these needs. Our estimates for the year 1994 show that 4.9% of the total budget available to public health care institutions was dedicated to hospital services provided to the elderly. Conclusions. In Mexico, the aged population health needs are already a priority, due to the particular nature of their needs and demand. Taking care of this population demands an important fraction of the resources spent in hospital services. To correctly plan and allocate resources for providing health care to this population developing a research agenda is an important requirement.