Myocardial work em pacientes estratificados pelo escore hfa-peff na insuficiência cardíaca com fração de ejeção preservada / Myocardial work in patients stratified by hfa-peff score in heart failure with preserved ejection fraction

INTRODUÇÃO: A insuficiência cardíaca (IC) com fração de ejeção preservada (ICFEP) consiste em pelo menos metade dos casos de IC. A abordagem é desafiadora e os critérios diagnósticos propostos pela Heart Failure Association (HFA) incluem dados ecocardiográficos oriundos da análise de deformação miocárdica longitudinal do ventrículo esquerdo (VE), como método para estimar a disfunção sistólica incipiente. Mais recentemente, os índices de trabalho miocárdico, myocardial work (MW), têm sido utilizados, em diversos contextos clínicos, como novas ferramentas não invasivas mais independentes de carga para avaliação da performance miocárdica comparada ao strain. OBJETIVO: Avaliar os índices de MW em diferentes categorias de probabilidade diagnóstica de ICFEP baseadas no escore multiparamétrico HFA-PEFF. MÉTODO: Estudo unicêntrico, transversal, descritivo, de pacientes ambulatoriais em centro cardiovascular especializado de ICFEP, avaliados de 2020-2023. Avaliaram-se 300 pacientes com suspeita diagnóstica de ICFEP com janela acústica apropriada, em ritmo sinusal, sem valvopatias significativas ou marcapasso, a partir de software ecocardiográfico comercialmente disponível para análise do strain bidimensional do VE por técnica de speckle tracking e do MW. A pressão arterial sistólica obtida por método padronizado por esfigmomanômetro braquial automático foi utilizada como substituta da pressão sistólica do VE para avaliação do MW. Análises estatísticas foram realizadas por meio do software SPSS. RESULTADOS: Amostra com idade média de 60±12.1 anos, fração de ejeção VE média de 59.3±5.1%, com 64% dos pacientes do sexo feminino. Hipertensão arterial sistêmica e dislipidemia foram altamente prevalentes (> 70%). Cerca de 54% e 18% dos pacientes foram categorizados em intermediária e alta probabilidade de ICFEP, respectivamente, pelo escore. O trabalho miocárdico desperdiçado - Global Wasted Work ­ GWW - apresentou tendência crescente do grupo de baixa probabilidade para o de alta probabilidade (81.8±43.1 / 117.9±75.3 / 154.7±93.1 mmHg%; p<0.001), com decréscimo progressivo da eficiência de trabalho - Global Work Efficiency ­ GWE (95.6±1.9 / 94±3.6 / 92±4.5%; p<0.001). O GWW exibiu área sob a curva ROC de 0.78 (0.70-0.84) para predição do grupo com alto escore HFA-PEFF. CONCLUSÃO: O MW consiste em ferramenta capaz de discriminar pacientes com suspeita diagnóstica de ICFEP, apresentando potencial utilidade na caracterização da performance miocárdica nessa doença.

Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals

The SARS-CoV-2 Gamma variant spread rapidly across Brazil, causing substantial infection and death waves. We use individual-level patient records following hospitalisation with suspected or confirmed COVID-19 to document the extensive shocks in hospital fatality rates that followed Gammas spread across 14 state capitals, and in which more than half of hospitalised patients died over sustained time periods. We show that extensive fluctuations in COVID-19 in-hospital fatality rates also existed prior to Gammas detection, and were largely transient after Gammas detection, subsiding with hospital demand. Using a Bayesian fatality rate model, we find that the geographic and temporal fluctuations in Brazils COVID-19 in-hospital fatality rates are primarily associated with geographic inequities and shortages in healthcare capacity. We project that approximately half of Brazils COVID-19 deaths in hospitals could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization, and pandemic preparedness are critical to minimize population wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries. NoteThe following manuscript has appeared as Report 46 - Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals at https://spiral.imperial.ac.uk:8443/handle/10044/1/91875. One sentence summaryCOVID-19 in-hospital fatality rates fluctuate dramatically in Brazil, and these fluctuations are primarily associated with geographic inequities and shortages in healthcare capacity.

Genomics and epidemiology of a novel SARS-CoV-2 lineage in Manaus, Brazil

Cases of SARS-CoV-2 infection in Manaus, Brazil, resurged in late 2020, despite high levels of previous infection there. Through genome sequencing of viruses sampled in Manaus between November 2020 and January 2021, we identified the emergence and circulation of a novel SARS-CoV-2 variant of concern, lineage P.1, that acquired 17 mutations, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased binding to the human ACE2 receptor. Molecular clock analysis shows that P.1 emergence occurred around early November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.4-2.2 times more transmissible and 25-61% more likely to evade protective immunity elicited by previous infection with non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness. One-Sentence SummaryWe report the evolution and emergence of a SARS-CoV-2 lineage of concern associated with rapid transmission in Manaus.