RESUMEN

Ebola virus disease poses a recurring risk to human health. We conducted a systematic review (PROSPERO CRD42023393345) of Ebola virus disease transmission models and parameters published from database inception to July 7, 2023, from PubMed and Web of Science. Two people screened each abstract and full text. Papers were extracted with a bespoke Access database, 10% were double extracted. We extracted 1280 parameters and 295 models from 522 papers. Basic reproduction number estimates were highly variable, as were effective reproduction numbers, likely reflecting spatiotemporal variability in interventions. Random-effect estimates were 15·4 days (95% CI 13·2-17·5) for the serial interval, 8·5 days (7·7-9·2) for the incubation period, 9·3 days (8·5-10·1) for the symptom-onset-to-death delay, and 13·0 days (10·4-15·7) for symptom-onset-to-recovery. Common effect estimates were similar, albeit with narrower CIs. Case-fatality ratio estimates were generally high but highly variable, which could reflect heterogeneity in underlying risk factors. Although a substantial body of literature exists on Ebola virus disease models and epidemiological parameter estimates, many of these studies focus on the west African Ebola epidemic and are primarily associated with Zaire Ebola virus, which leaves a key gap in our knowledge regarding other Ebola virus species and outbreak contexts.

RESUMEN

Advancements in cancer treatment have led to improved survival rates, with early phase clinical trials (EPCTs) serving as important initial steps in evaluating novel therapies. Recent studies have shown that response rates in these trials have doubled in the last twenty years. Patients who enroll on EPCTs have advanced cancer and heightened symptomatology yet maintain a robust performance status that qualifies them for clinical trial participation. It is well established that many of these patients have needs that can be addressed by palliative care, including symptom management, value assessments, advance care planning, and psychosocial and spiritual support. Several small studies have aimed to identify the most beneficial palliative care intervention for this cohort of patients, ranging from formal clinic-based multidisciplinary palliative care interventions to home-based interventions. While outcomes have trended towards benefit for patients, especially pertaining to psychological well-being, most studies were not powered to detect additional benefits for improved physical symptom management, reduction in care utilization or increased length of time on trial. In this review, we discuss the unique palliative care needs of this population and what we can learn from results of past interventional studies. We advocate for a tailored palliative care approach that acknowledges the time toxicity experienced by patients enrolled in EPCTs and address challenges posed by shortages within the palliative care workforce.

Asunto(s)

Neoplasias , Cuidados Paliativos , Humanos , Cuidados Paliativos/métodos , Neoplasias/terapia , Neoplasias/psicología , Ensayos Clínicos como Asunto , Planificación Anticipada de Atención

RESUMEN

BACKGROUND: The effects of spinal versus general anesthesia on long-term outcomes have not been well studied. This study tested the hypothesis that spinal anesthesia is associated with better long-term survival and functional recovery than general anesthesia. METHODS: A prespecified analysis was conducted of long-term outcomes of a completed randomized superiority trial that compared spinal anesthesia versus general anesthesia for hip fracture repair. Participants included previously ambulatory patients 50 yr of age or older at 46 U.S. and Canadian hospitals. Patients were randomized 1:1 to spinal or general anesthesia, stratified by sex, fracture type, and study site. Outcome assessors and investigators involved in the data analysis were masked to the treatment arm. Outcomes included survival at up to 365 days after randomization (primary); recovery of ambulation among 365-day survivors; and composite endpoints for death or new inability to ambulate and death or new nursing home residence at 365 days. Patients were included in the analysis as randomized. RESULTS: A total of 1,600 patients were enrolled between February 12, 2016, and February 18, 2021; 795 were assigned to spinal anesthesia, and 805 were assigned to general anesthesia. Among 1,599 patients who underwent surgery, vital status information at or beyond the final study interview (conducted at approximately 365 days after randomization) was available for 1,427 (89.2%). Survival did not differ by treatment arm; at 365 days after randomization, there were 98 deaths in patients assigned to spinal anesthesia versus 92 deaths in patients assigned to general anesthesia (hazard ratio, 1.08; 95% CI, 0.81 to 1.44, P = 0.59). Recovery of ambulation among patients who survived a year did not differ by type of anesthesia (adjusted odds ratio for spinal vs. general, 0.87; 95% CI, 0.67 to 1.14; P = 0.31). Other outcomes did not differ by treatment arm. CONCLUSIONS: Long-term outcomes were similar with spinal versus general anesthesia.

Asunto(s)

Anestesia Raquidea , Fracturas de Cadera , Humanos , Anestesia General , Canadá/epidemiología , Fracturas de Cadera/cirugía , Resultado del Tratamiento , Masculino , Femenino , Persona de Mediana Edad , Anciano

RESUMEN

Reported COVID-19 cases and associated mortality remain low in many sub-Saharan countries relative to global averages, but true impact is difficult to estimate given limitations around surveillance and mortality registration. In Lusaka, Zambia, burial registration and SARS-CoV-2 prevalence data during 2020 allow estimation of excess mortality and transmission. Relative to pre-pandemic patterns, we estimate age-dependent mortality increases, totalling 3212 excess deaths (95% CrI: 2104-4591), representing an 18.5% (95% CrI: 13.0-25.2%) increase relative to pre-pandemic levels. Using a dynamical model-based inferential framework, we find that these mortality patterns and SARS-CoV-2 prevalence data are in agreement with established COVID-19 severity estimates. Our results support hypotheses that COVID-19 impact in Lusaka during 2020 was consistent with COVID-19 epidemics elsewhere, without requiring exceptional explanations for low reported figures. For more equitable decision-making during future pandemics, barriers to ascertaining attributable mortality in low-income settings must be addressed and factored into discourse around reported impact differences.

Asunto(s)

COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Zambia/epidemiología , Entierro , Pandemias

RESUMEN

Not all COVID-19 deaths are officially reported, and particularly in low-income and humanitarian settings, the magnitude of reporting gaps remains sparsely characterized. Alternative data sources, including burial site worker reports, satellite imagery of cemeteries, and social media-conducted surveys of infection may offer solutions. By merging these data with independently conducted, representative serological studies within a mathematical modeling framework, we aim to better understand the range of underreporting using examples from three major cities: Addis Ababa (Ethiopia), Aden (Yemen), and Khartoum (Sudan) during 2020. We estimate that 69 to 100%, 0.8 to 8.0%, and 3.0 to 6.0% of COVID-19 deaths were reported in each setting, respectively. In future epidemics, and in settings where vital registration systems are limited, using multiple alternative data sources could provide critically needed, improved estimates of epidemic impact. However, ultimately, these systems are needed to ensure that, in contrast to COVID-19, the impact of future pandemics or other drivers of mortality is reported and understood worldwide.

Asunto(s)

COVID-19 , Humanos , COVID-19/epidemiología , Etiopía/epidemiología , Encuestas y Cuestionarios , Pandemias

RESUMEN

INTRODUCTION: The effect of spinal versus general anesthesia on the risk of postoperative delirium or other outcomes for patients with or without cognitive impairment (including dementia) is unknown. METHODS: Post hoc secondary analysis of a multicenter pragmatic trial comparing spinal versus general anesthesia for adults aged 50 years or older undergoing hip fracture surgery. RESULTS: Among patients randomized to spinal versus general anesthesia, new or worsened delirium occurred in 100/295 (33.9%) versus 107/283 (37.8%; odds ratio [OR] 0.85; 95% confidence interval [CI] 0.60 to 1.19) among persons with cognitive impairment and 70/432 (16.2%) versus 71/445 (16.0%) among persons without cognitive impairment (OR 1.02; 95% CI 0.71 to 1.47, p = 0.46 for interaction). Delirium severity, in-hospital complications, and 60-day functional recovery did not differ by anesthesia type in patients with or without cognitive impairment. DISCUSSION: Anesthesia type is not associated with differences in delirium and functional outcomes among persons with or without cognitive impairment.

Asunto(s)

Disfunción Cognitiva , Delirio , Fracturas de Cadera , Humanos , Delirio/etiología , Complicaciones Posoperatorias , Disfunción Cognitiva/complicaciones , Anestesia General/efectos adversos , Fracturas de Cadera/complicaciones , Fracturas de Cadera/cirugía

RESUMEN

Background Frailty is prevalent in older adults with heart failure and is associated with poor outcomes; however, there remains uncertainty on how to measure frailty in clinical practice. Methods and Results A multicentric prospective cohort study was assembled at 4 heart failure clinics to compare the prognostic value of 3 physical frailty scales in ambulatory patients with heart failure. Outcomes were all-cause death or hospitalization and health-related quality of life using the 36-Item Short Form survey questionnaire (SF-36) at 3 months. Multivariable regression was adjusted for age, sex, Meta-Analysis Global Group in Chronic Heart Failure score, and baseline SF-36 score. The cohort included 215 patients (mean age 77.6 years). All 3 frailty scales were independently associated with death or hospitalization at 3 months; the adjusted odds ratios standardized per 1 SD worsening of the Short Physical Performance Battery; Fried, and strength, assistance with walking, rising from a chair, climbing stairs, and falls scales were 1.67 (95% CI, 1.09-2.55), 1.60 (95% CI, 1.04-2.46), and 1.55 (95% CI, 1.03-2.35), respectively, with C statistics of 0.77 to 0.78. All 3 frailty scales were independently associated with worsening SF-36 scores, especially the Short Physical Performance Battery, for which 1 SD worsening of frailty translated to a decrement of -5.86 (-8.55 to -3.17) and -5.51 (-7.82 to -3.21) points in the Physical Component Score and Mental Component Score. Conclusions All 3 physical frailty scales were associated with death, hospitalization, and reduced health-related quality of life in ambulatory patients with heart failure. Questionnaire or performance-based physical frailty scales can be used to offer prognostic value and a therapeutic target in this vulnerable population. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03887351.

Asunto(s)

Fragilidad , Insuficiencia Cardíaca , Humanos , Anciano , Fragilidad/diagnóstico , Fragilidad/complicaciones , Calidad de Vida , Estudios Prospectivos , Insuficiencia Cardíaca/tratamiento farmacológico , Encuestas y Cuestionarios

RESUMEN

BACKGROUND: The REGAIN (Regional versus General Anesthesia for Promoting Independence after Hip Fracture) trial found similar ambulation and survival at 60 days with spinal versus general anesthesia for hip fracture surgery. Trial outcomes evaluating pain, prescription analgesic use, and patient satisfaction have not yet been reported. OBJECTIVE: To compare pain, analgesic use, and satisfaction after hip fracture surgery with spinal versus general anesthesia. DESIGN: Preplanned secondary analysis of a pragmatic randomized trial. (ClinicalTrials.gov: NCT02507505). SETTING: 46 U.S. and Canadian hospitals. PARTICIPANTS: Patients aged 50 years or older undergoing hip fracture surgery. INTERVENTION: Spinal or general anesthesia. MEASUREMENTS: Pain on postoperative days 1 through 3; 60-, 180-, and 365-day pain and prescription analgesic use; and satisfaction with care. RESULTS: A total of 1600 patients were enrolled. The average age was 78 years, and 77% were women. A total of 73.5% (1050 of 1428) of patients reported severe pain during the first 24 hours after surgery. Worst pain over the first 24 hours after surgery was greater with spinal anesthesia (rated from 0 [no pain] to 10 [worst pain imaginable]; mean difference, 0.40 [95% CI, 0.12 to 0.68]). Pain did not differ across groups at other time points. Prescription analgesic use at 60 days occurred in 25% (141 of 563) and 18.8% (108 of 574) of patients assigned to spinal and general anesthesia, respectively (relative risk, 1.33 [CI, 1.06 to 1.65]). Satisfaction was similar across groups. LIMITATION: Missing outcome data and multiple outcomes assessed. CONCLUSION: Severe pain is common after hip fracture. Spinal anesthesia was associated with more pain in the first 24 hours after surgery and more prescription analgesic use at 60 days compared with general anesthesia. PRIMARY FUNDING SOURCE: Patient-Centered Outcomes Research Institute.

Asunto(s)

Anestesia Raquidea , Fracturas de Cadera , Anciano , Analgésicos/uso terapéutico , Anestesia General/efectos adversos , Anestesia Raquidea/efectos adversos , Canadá , Femenino , Fracturas de Cadera/cirugía , Humanos , Masculino , Dolor , Dolor Postoperatorio/tratamiento farmacológico , Satisfacción del Paciente

RESUMEN

BACKGROUND: The effects of spinal anesthesia as compared with general anesthesia on the ability to walk in older adults undergoing surgery for hip fracture have not been well studied. METHODS: We conducted a pragmatic, randomized superiority trial to evaluate spinal anesthesia as compared with general anesthesia in previously ambulatory patients 50 years of age or older who were undergoing surgery for hip fracture at 46 U.S. and Canadian hospitals. Patients were randomly assigned in a 1:1 ratio to receive spinal or general anesthesia. The primary outcome was a composite of death or an inability to walk approximately 10 ft (3 m) independently or with a walker or cane at 60 days after randomization. Secondary outcomes included death within 60 days, delirium, time to discharge, and ambulation at 60 days. RESULTS: A total of 1600 patients were enrolled; 795 were assigned to receive spinal anesthesia and 805 to receive general anesthesia. The mean age was 78 years, and 67.0% of the patients were women. A total of 666 patients (83.8%) assigned to spinal anesthesia and 769 patients (95.5%) assigned to general anesthesia received their assigned anesthesia. Among patients in the modified intention-to-treat population for whom data were available, the composite primary outcome occurred in 132 of 712 patients (18.5%) in the spinal anesthesia group and 132 of 733 (18.0%) in the general anesthesia group (relative risk, 1.03; 95% confidence interval [CI], 0.84 to 1.27; P = 0.83). An inability to walk independently at 60 days was reported in 104 of 684 patients (15.2%) and 101 of 702 patients (14.4%), respectively (relative risk, 1.06; 95% CI, 0.82 to 1.36), and death within 60 days occurred in 30 of 768 (3.9%) and 32 of 784 (4.1%), respectively (relative risk, 0.97; 95% CI, 0.59 to 1.57). Delirium occurred in 130 of 633 patients (20.5%) in the spinal anesthesia group and in 124 of 629 (19.7%) in the general anesthesia group (relative risk, 1.04; 95% CI, 0.84 to 1.30). CONCLUSIONS: Spinal anesthesia for hip-fracture surgery in older adults was not superior to general anesthesia with respect to survival and recovery of ambulation at 60 days. The incidence of postoperative delirium was similar with the two types of anesthesia. (Funded by the Patient-Centered Outcomes Research Institute; REGAIN ClinicalTrials.gov number, NCT02507505.).

Asunto(s)

Anestesia General , Anestesia Raquidea , Delirio/etiología , Fracturas de Cadera/cirugía , Anciano , Anciano de 80 o más Años , Anestesia General/efectos adversos , Anestesia Raquidea/efectos adversos , Delirio/epidemiología , Femenino , Fracturas de Cadera/mortalidad , Fracturas de Cadera/fisiopatología , Humanos , Incidencia , Masculino , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Recuperación de la Función

RESUMEN

AbstractPlasmids are extrachromosomal segments of DNA that can transfer genes between bacterial cells. Many plasmid genes benefit bacteria but cause harm to human health by granting antibiotic resistance to pathogens. Transfer rate is a key parameter for predicting plasmid dynamics, but observed rates are highly variable, and the effects of selective forces on their evolution are unclear. We apply evolutionary analysis to plasmid conjugation models to investigate selective pressures affecting plasmid transfer rate, emphasizing host versus plasmid control, the costs of plasmid transfer, and the role of recipient cells. Our analyses show that plasmid-determined transfer rates can be predicted with three parameters (host growth rate, plasmid loss rate, and the cost of plasmid transfer on growth) under some conditions. We also show that low-frequency genetic variation in transfer rate can accumulate, facilitating rapid adaptation to changing conditions. Furthermore, reduced transfer rates due to host control have limited effects on plasmid prevalence until low enough to prevent plasmid persistence. These results provide a framework to predict plasmid transfer rate evolution in different environments and demonstrate the limited impact of host mechanisms to control the costs incurred when plasmids are present.

Asunto(s)

Bacterias , Transferencia de Gen Horizontal , Adaptación Fisiológica , Bacterias/genética , Farmacorresistencia Microbiana , Humanos , Plásmidos/genética

RESUMEN

BACKGROUND: Peripartum cardiomyopathy (PPCM) occurs in ≈1:2000 deliveries in the United States and worldwide. The genetic underpinnings of PPCM remain poorly defined. Approximately 10% of women with PPCM harbor truncating variants in TTN (TTNtvs). Whether mutations in other genes can predispose to PPCM is not known. It is also not known if the presence of TTNtvs predicts clinical presentation or outcomes. Nor is it known if the prevalence of TTNtvs differs in women with PPCM and preeclampsia, the strongest risk factor for PPCM. METHODS: Women with PPCM were retrospectively identified from several US and international academic centers, and clinical information and DNA samples were acquired. Next-generation sequencing was performed on 67 genes, including TTN, and evaluated for burden of truncating and missense variants. The impact of TTNtvs on the severity of clinical presentation, and on clinical outcomes, was evaluated. RESULTS: Four hundred sixty-nine women met inclusion criteria. Of the women with PPCM, 10.4% bore TTNtvs (odds ratio=9.4 compared with 1.2% in the reference population; Bonferroni-corrected P [P*]=1.2×10-46). We additionally identified overrepresentation of truncating variants in FLNC (odds ratio=24.8, P*=7.0×10-8), DSP (odds ratio=14.9, P*=1.0×10-8), and BAG3 (odds ratio=53.1, P*=0.02), genes not previously associated with PPCM. This profile is highly similar to that found in nonischemic dilated cardiomyopathy. Women with TTNtvs had lower left ventricular ejection fraction on presentation than did women without TTNtvs (23.5% versus 29%, P=2.5×10-4), but did not differ significantly in timing of presentation after delivery, in prevalence of preeclampsia, or in rates of clinical recovery. CONCLUSIONS: This study provides the first extensive genetic and phenotypic landscape of PPCM and demonstrates that predisposition to heart failure is an important risk factor for PPCM. The work reveals a degree of genetic similarity between PPCM and dilated cardiomyopathy, suggesting that gene-specific therapeutic approaches being developed for dilated cardiomyopathy may also apply to PPCM, and that approaches to genetic testing in PPCM should mirror those taken in dilated cardiomyopathy. Last, the clarification of genotype/phenotype associations has important implications for genetic counseling.

Asunto(s)

Cardiomiopatías/genética , Periodo Periparto/genética , Adulto , Cardiomiopatías/fisiopatología , Femenino , Humanos , Fenotipo , Embarazo , Estudios Retrospectivos

RESUMEN

Plasmids transfer at highly variable rates that spread over 10 orders of magnitude. While rates have been measured for decades and it is known that the rates are affected bysome biotic and abiotic factors, it is unclear how and to what extent these factors determine the rates of transfer. We performed a meta-analysis of 1224 published transfer rates from 33 papers (filtered to 612 transfer rates) to assess this variation. Over three quarters of the variation can be predicted, with plasmid repression and media type (solid versus liquid) identified as general variables explaining the most variation. Of the host and plasmid identities, identity of the recipient bacterium explained the most variation, up to 34% in some models, and more than any other explanatory variable. These results emphasize the role of the recipient in determining the rate of transfer, and show an improved range of transfer values and their correlates that can be used in future when modeling plasmid persistence.

Asunto(s)

Conjugación Genética , Transferencia de Gen Horizontal , Plásmidos/genética , Algoritmos , Bacterias/genética , Escherichia coli/genética , Modelos Biológicos

RESUMEN

Importance: The prevalence of nonischemic dilated cardiomyopathy (DCM) is greater in individuals of African ancestry than in individuals of European ancestry. However, little is known about whether the difference in prevalence or outcomes is associated with functional genetic variants. Objective: We hypothesized that Bcl2-associated anthanogene 3 (BAG3) genetic variants were associated with outcomes in individuals of African ancestry with DCM. Design: This multicohort study of the BAG3 genotype in patients of African ancestry with dilated cardiomyopathy uses DNA obtained from African American individuals enrolled in 3 clinical studies: the Genetic Risk Assessment of African Americans With Heart Failure (GRAHF) study; the Intervention in Myocarditis and Acute Cardiomyopathy Trial-2 (IMAC-2) study; and the Genetic Risk Assessment of Cardiac Events (GRACE) study. Samples of DNA were also acquired from the left ventricular myocardium of patients of African ancestry who underwent heart transplant at the University of Colorado and University of Pittsburgh. Main Outcomes and Measures: The primary end points were the prevalence of BAG3 mutations in African American individuals and event-free survival in participants harboring functional BAG3 mutations. Results: Four BAG3 genetic variants were identified; these were expressed in 42 of 402 African American individuals (10.4%) with nonischemic heart failure and 9 of 107 African American individuals (8.4%) with ischemic heart failure but were not present in a reference population of European ancestry (P < .001). The variants included 2 nonsynonymous single-nucleotide variants; 1 three-nucleotide in-frame insertion; and 2 single-nucleotide variants that were linked in cis. The presence of BAG3 variants was associated with a nearly 2-fold (hazard ratio, 1.97 [95% CI, 1.19-3.24]; P = .01) increase in cardiac events in carriers compared with noncarriers. Transfection of transformed adult human ventricular myocytes with plasmids expressing the 4 variants demonstrated that each variant caused an increase in apoptosis and a decrease in autophagy when samples were subjected to the stress of hypoxia-reoxygenation. Conclusions and Relevance: This study demonstrates that genetic variants in BAG3 found almost exclusively in individuals of African ancestry were not causative of disease but were associated with a negative outcome in patients with a dilated cardiomyopathy through modulation of the function of BAG3. The results emphasize the importance of biological differences in causing phenotypic variance across diverse patient populations, the need to include diverse populations in genetic cohorts, and the importance of determining the pathogenicity of genetic variants.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Reguladoras de la Apoptosis/genética , Negro o Afroamericano/genética , Cardiomiopatía Dilatada/etnología , Mutación , Población Blanca/genética , Animales , Cardiomiopatía Dilatada/genética , Estudios de Casos y Controles , Modelos Animales de Enfermedad , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Ratones , Prevalencia , Pronóstico , Análisis de Secuencia de ADN , Análisis de Supervivencia

RESUMEN

AIM: To evaluate the impact of AGTR1 A1166C (rs5186) on the response to candesartan in patients with heart failure. MATERIALS & METHODS: Prospective, multicentre, open-label study. We studied 299 symptomatic patients with heart failure presenting a left ventricular ejection fraction ≤40%. RESULTS: Reductions in the primary end points of natriuretic peptides were not significantly associated with AGTR1 A1166C. Nevertheless, carrying the 1166C allele was associated with a greater compensatory increase in renin activity (p = 0.037) after 16 weeks of treatment with candesartan and a more modest effect on aldosterone concentrations (p = 0.022). CONCLUSION: AGTR1 1166C carriers may experience a greater long-term compensatory renin-angiotensin-aldosterone system activation following treatment with candesartan. Whether these associations ultimately influence clinical outcomes requires investigation. Clinicaltrials.gov : NCT00400582.

Asunto(s)

Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Bencimidazoles/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Polimorfismo de Nucleótido Simple , Receptor de Angiotensina Tipo 1/genética , Sistema Renina-Angiotensina/efectos de los fármacos , Tetrazoles/uso terapéutico , Anciano , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacocinética , Bencimidazoles/farmacocinética , Biomarcadores/sangre , Compuestos de Bifenilo , Presión Sanguínea/efectos de los fármacos , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/genética , Humanos , Pruebas de Función Renal , Masculino , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Farmacogenética , Estudios Prospectivos , Sistema Renina-Angiotensina/genética , Tetrazoles/farmacocinética , Resultado del Tratamiento

RESUMEN

BACKGROUND: Among various cardiac autoantibodies (AAbs), those recognizing the ß1-adrenergic receptor (ß1AR) demonstrate agonist-like effects and induce myocardial damage that can be reversed by ß-blockers and immunoglobulin G3 (IgG3) immunoadsorption. OBJECTIVES: The goal of this study was to investigate the role of ß1AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy. METHODS: Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction [LVEF] ≤0.40; <6 months). The presence of IgG and IgG3-ß1AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months. RESULTS: Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-ß1AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p < 0.01; left ventricular end-systolic diameter, p = 0.03). At 6 months, LVEF was significantly higher in the IgG3 group (p = 0.007). Multiple regression analysis showed that IgG3-ß1AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, ß = 0.20, p = 0.01; change in LVEF, ß = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint. CONCLUSIONS: IgG3-ß1AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.

Asunto(s)

Antagonistas Adrenérgicos beta/uso terapéutico , Autoanticuerpos/sangre , Insuficiencia Cardíaca Sistólica/sangre , Receptores Adrenérgicos beta 1/inmunología , Adulto , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca Sistólica/tratamiento farmacológico , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recuperación de la Función , Resultado del Tratamiento , Función Ventricular Izquierda

RESUMEN

BACKGROUND: Peripartum cardiomyopathy has variable disease progression and left ventricular (LV) recovery. We hypothesized that baseline right ventricular (RV) size and function are associated with LV recovery and outcome. METHODS AND RESULTS: Investigations of Pregnancy-Associated Cardiomyopathy was a prospective 30-center study of 100 peripartum cardiomyopathy women with LV ejection fraction (LVEF) <45% within 13 weeks after delivery. Baseline RV function was assessed by echocardiographic end-diastolic area, end-systolic area, fractional area change, tricuspid annular plane excursion, and RV speckle-tracking longitudinal strain. LV recovery was defined as LVEF of ≥50% at 1 year, persistent severe LV dysfunction as LVEF of ≤35%, and major events as death, transplant, or LV assist device implantation. RV measurements were feasible for 90 of the 96 patients (94%) with echocardiograms available. Mean baseline LVEF was 36±9%. RV fractional area change was <35% in 38% of patients. Of 84 patients with 1-year follow-up data, 63 (75%) had LV recovery and 11 (13%) had LVEF of ≤35% or a major event (4 LV assist devices and 2 deaths). Tricuspid annular plane excursion and RV strain did not predict outcome. Baseline RV fractional area change by multivariable analysis was independently associated with subsequent LV recovery and clinical outcome. CONCLUSIONS: Peripartum cardiomyopathy patients had a high incidence of LV recovery, but a significant minority had persistent LV dysfunction or a major clinical event by 1 year. RV function per echocardiographic fractional area change at presentation was associated with subsequent LV recovery and clinical outcomes and thus is prognostically important.

Asunto(s)

Cardiomiopatías/fisiopatología , Periodo Periparto , Complicaciones Cardiovasculares del Embarazo/fisiopatología , Disfunción Ventricular Izquierda/fisiopatología , Función Ventricular Izquierda , Función Ventricular Derecha , Área Bajo la Curva , Canadá , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/mortalidad , Cardiomiopatías/terapia , Ecocardiografía , Femenino , Humanos , Estimación de Kaplan-Meier , Valor Predictivo de las Pruebas , Embarazo , Complicaciones Cardiovasculares del Embarazo/diagnóstico por imagen , Complicaciones Cardiovasculares del Embarazo/mortalidad , Complicaciones Cardiovasculares del Embarazo/terapia , Pronóstico , Estudios Prospectivos , Curva ROC , Recuperación de la Función , Factores de Riesgo , Volumen Sistólico , Factores de Tiempo , Estados Unidos , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/mortalidad , Disfunción Ventricular Izquierda/terapia

RESUMEN

BACKGROUND: Black women are at greater risk for peripartum cardiomyopathy (PPCM). The guanine nucleotide-binding proteins ß-3 subunit (GNB3) has a polymorphism C825T. The GNB3 TT genotype more prevalent in blacks is associated with poorer outcomes. We evaluated GNB3 genotype and myocardial recovery in PPCM. METHODS AND RESULTS: A total of 97 women with PPCM were enrolled and genotyped for the GNB3 T/C polymorphism. Left ventricular ejection fraction (LVEF) was assessed by echocardiography at entry, 6 and 12 months postpartum. LVEF over time in subjects with the GNB3 TT genotype was compared with those with the C allele overall and in black and white subsets. The cohort was 30% black, age 30+6, LVEF 0.34+0.10 at entry 31+25 days postpartum. The % GNB3 genotype for TT/CT/CC=23/41/36 and differed markedly by race (blacks=52/38/10 versus whites=10/44/46, P<0.001). In subjects with the TT genotype, LVEF at entry was lower (TT=0.31+0.09; CT+CC=0.35+0.09, P=0.054) and this difference increased at 6 (TT=0.45+0.15; CT+CC=0.53+0.08, P=0.002) and 12 months (TT=0.45+0.15; CT+CC=0.56+0.07, P<0.001.). The difference in LVEF at 12 months by genotype was most pronounced in blacks (12 months LVEF for GNB3 TT=0.39+0.16; versus CT+CC=0.53+0.09, P=0.02) but evident in whites (TT=0.50++0.11; CT+CC=0.56+0.06, P=0.04). CONCLUSIONS: The GNB3 TT genotype was associated with lower LVEF at 6 and 12 months in women with PPCM, and this was particularly evident in blacks. Racial differences in the prevalence and impact of GNB3 TT may contribute to poorer outcomes in black women with PPCM.

Asunto(s)

Cardiomiopatías/genética , Proteínas de Unión al GTP Heterotriméricas/genética , Polimorfismo Genético , Complicaciones Cardiovasculares del Embarazo/genética , Adulto , Negro o Afroamericano/genética , Canadá/epidemiología , Cardiomiopatías/diagnóstico , Cardiomiopatías/enzimología , Cardiomiopatías/etnología , Cardiomiopatías/fisiopatología , Supervivencia sin Enfermedad , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Periodo Periparto , Fenotipo , Embarazo , Complicaciones Cardiovasculares del Embarazo/diagnóstico , Complicaciones Cardiovasculares del Embarazo/enzimología , Complicaciones Cardiovasculares del Embarazo/etnología , Complicaciones Cardiovasculares del Embarazo/fisiopatología , Prevalencia , Factores Protectores , Recuperación de la Función , Factores de Riesgo , Volumen Sistólico , Factores de Tiempo , Estados Unidos/epidemiología , Función Ventricular Izquierda , Población Blanca/genética , Adulto Joven

RESUMEN

Background Peripartum cardiomyopathy shares some clinical features with idiopathic dilated cardiomyopathy, a disorder caused by mutations in more than 40 genes, including TTN, which encodes the sarcomere protein titin. Methods In 172 women with peripartum cardiomyopathy, we sequenced 43 genes with variants that have been associated with dilated cardiomyopathy. We compared the prevalence of different variant types (nonsense, frameshift, and splicing) in these women with the prevalence of such variants in persons with dilated cardiomyopathy and with population controls. Results We identified 26 distinct, rare truncating variants in eight genes among women with peripartum cardiomyopathy. The prevalence of truncating variants (26 in 172 [15%]) was significantly higher than that in a reference population of 60,706 persons (4.7%, P=1.3×10(-7)) but was similar to that in a cohort of patients with dilated cardiomyopathy (55 of 332 patients [17%], P=0.81). Two thirds of identified truncating variants were in TTN, as seen in 10% of the patients and in 1.4% of the reference population (P=2.7×10(-10)); almost all TTN variants were located in the titin A-band. Seven of the TTN truncating variants were previously reported in patients with idiopathic dilated cardiomyopathy. In a clinically well-characterized cohort of 83 women with peripartum cardiomyopathy, the presence of TTN truncating variants was significantly correlated with a lower ejection fraction at 1-year follow-up (P=0.005). Conclusions The distribution of truncating variants in a large series of women with peripartum cardiomyopathy was remarkably similar to that found in patients with idiopathic dilated cardiomyopathy. TTN truncating variants were the most prevalent genetic predisposition in each disorder.

Asunto(s)

Cardiomiopatías/genética , Cardiomiopatía Dilatada/genética , Conectina/genética , Predisposición Genética a la Enfermedad , Mutación , Periodo Periparto , Complicaciones Cardiovasculares del Embarazo/genética , Adulto , Estudios de Casos y Controles , Conectina/química , Femenino , Humanos , Embarazo , Isoformas de Proteínas , Análisis de Secuencia de ADN , Volumen Sistólico

RESUMEN

AIMS: Patients with recent onset non-ischaemic cardiomyopathy have a variable clinical course with respect to recovery of left ventricular ejection fraction (LVEF). The aim of this study was to understand whether temporal changes in diastolic function (DF) are associated with clinical outcomes independent of LVEF recovery. METHODS AND RESULTS: The Intervention in Myocarditis and Acute Cardiomyopathy (IMAC)-2 study was a prospective, multicentre trial investigating myocardial recovery in subjects with symptoms onset of <6 months and LVEF ≤40% of non-ischaemic dilated cardiomyopathy related to idiopathic cardiomyopathy or myocarditis. LVEF and DF were measured at presentation and at 6-month follow-up. Of 147 patients (mean age 46 ± 14 years, 40% female), baseline LVEF was 23 ± 8%. At 6 months, LVEF improved to 41 ± 12%, with 71% increasing by at least 10% ejection fraction units. DF improved in 58%, was unchanged in 28%, and worsened in 14%. Over a mean follow-up of 1.8 ± 1.2 years, there were 18 events: 11 heart failure (HF) hospitalizations, 3 deaths, and 4 heart transplants. LVEF (HR = 0.94, 95% CI 0.91-0.98, P = 0.002) and DF improvements at 6 months (HR = 0.32, 95% CI 0.11-0.92, P = 0.03) were independently associated with lower likelihood for the combined end point of death, transplantation, and HF hospitalization. Diastolic functional improvement at 6-month follow-up was as prognostically important as LVEF recovery for these patients, and provided incremental prognostic value to the risk stratification (X(2) increased from 12.6 to 18, P = 0.02). CONCLUSION: In patients with recent onset non-ischaemic cardiomyopathy, DF recovery was associated with favourable outcomes independent of LVEF improvement, adding incremental prognostic value to these patients.

Asunto(s)

Cardiomiopatía Dilatada/diagnóstico por imagen , Cardiomiopatía Dilatada/fisiopatología , Ecocardiografía , Volumen Sistólico/fisiología , Remodelación Ventricular/fisiología , Enfermedad Aguda , Adulto , Diástole/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Tiempo