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For many years, treatment of hypertrophic cardiomyopathy (HCM) has focused on non-disease-specific therapies. Cardiac myosin modulators (ie, mavacamten and aficamten) reduce the pathologic actin-myosin interactions that are characteristic of HCM, leading to improved cardiac energetics and reduction in hypercontractility. Several recently published randomized clinical trials have demonstrated that mavacamten improves exercise capacity, left ventricular outflow tract obstruction and symptoms in patients with obstructive HCM and may delay the need for septal-reduction therapy. Long-term data in real-world populations will be needed to fully assess the safety and efficacy of mavacamten. Importantly, HCM is a complex and heterogeneous disease, and not all patients will respond to mavacamten; therefore, careful patient selection and shared decision making will be necessary in guiding the use of mavacamten in obstructive HCM.
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BACKGROUND: Leukopenia in the early period following heart transplantation (HT) is not well-studied. The aim of this study was to evaluate risk factors for the development of post-transplant leukopenia and its consequences for HT recipients. METHODS: Adult patients at a large-volume transplant center who received HT between January 1, 2010 and December 31, 2020 were included. The incidence of leukopenia (WBC ≤3 × 103 /µL) in the first 90-days following HT, individual risk factors, and its effect on 1-year outcomes were evaluated. RESULTS: Of 506 HT recipients, 184 (36%) developed leukopenia within 90-days. Median duration of the first leukopenia episode was 15.5 days (IQR 8-42.5 days). Individuals who developed leukopenia had lower pre-transplant WBC counts compared to those who did not (6.1 × 103 /µL vs. 6.9 × 103 /µL, p = .02). Initial immunosuppressive and infectious chemoprophylactic regimens were not significantly different between groups. Early leukopenia was associated with a higher mortality at 1-year (6.6% vs. 2.1%, p = .008; adjusted HR 3.0) and an increased risk of recurrent episodes. Rates of infection and rejection were not significantly different between the two groups. CONCLUSIONS: Leukopenia in the early period following HT is common and associated with an increased risk of mortality. Further study is needed to identify individuals at highest risk for leukopenia prior to transplant and optimize immunosuppressive and infectious chemoprophylactic regimens for this subgroup.
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Transplante de Coração , Transplante de Rim , Leucopenia , Adulto , Humanos , Transplante de Rim/efeitos adversos , Leucopenia/epidemiologia , Leucopenia/etiologia , Imunossupressores/efeitos adversos , Fatores de Risco , Transplante de Coração/efeitos adversos , Transplantados , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Estudos RetrospectivosRESUMO
Many complex disease risk loci map to intergenic regions containing long intergenic noncoding RNAs (lincRNAs). The majority of these is not conserved outside humans, raising the question whether genetically regulated expression of non-conserved and conserved lincRNAs has similar rates of association with complex traits. Here we leveraged data from the Genotype-Tissue Expression (GTEx) project and multiple public genome-wide association study (GWAS) resources. Using an established transcriptome-wide association study (TWAS) tool, FUSION, we interrogated the associations between cis-regulated expression of lincRNAs and multiple cardiometabolic traits. We found that cis-regulated expression of non-conserved lincRNAs had a strikingly similar trend of association with complex cardiometabolic traits as conserved lincRNAs. This finding challenges the conventional notion of conservation that has led to prioritization of conserved loci for functional studies and calls attention to the need to develop comprehensive strategies to study the large number of non-conserved human lincRNAs that may contribute to human disease.
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Doenças Cardiovasculares , RNA Longo não Codificante , Estudo de Associação Genômica Ampla , Humanos , Herança Multifatorial , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , TranscriptomaRESUMO
OBJECTIVE: Transcriptome profiling of human tissues has revealed thousands of long intergenic noncoding RNAs (lincRNAs) at loci identified through large-scale genome-wide studies for complex cardiometabolic traits. This raises the question of whether genetic variation at nonconserved lincRNAs has any systematic association with complex disease, and if so, how different this pattern is from conserved lincRNAs. We evaluated whether the associations between nonconserved lincRNAs and 8 complex cardiometabolic traits resemble or differ from the pattern of association for conserved lincRNAs. Approach and Results: Our investigation of over 7000 lincRNA annotations from GENCODE Release 33-GRCh38.p13 for complex trait genetic associations leveraged several large, established meta-analyses genome-wide association study summary data resources, including GIANT (Genetic Investigation of Anthropometric Traits), UK Biobank, GLGC (Global Lipids Genetics Consortium), Cardiogram (Coronary Artery Disease Genome Wide Replication and Meta-Analysis), and DIAGRAM (Diabetes Genetics Replication and Meta-Analysis)/DIAMANTE (Diabetes Meta-Analysis of Trans-Ethnic Association Studies). These analyses revealed that (1) nonconserved lincRNAs associate with a range of cardiometabolic traits at a rate that is generally consistent with conserved lincRNAs; (2) these findings persist across different definitions of conservation; and (3) overall across all cardiometabolic traits, approximately one-third of genome-wide association study-associated lincRNAs are nonconserved, and this increases to about two-thirds using a more stringent definition of conservation. CONCLUSIONS: These findings suggest that the traditional notion of conservation driving prioritization for functional and translational follow-up of complex cardiometabolic genomic discoveries may need to be revised in the context of the abundance of nonconserved long noncoding RNAs in the human genome and their apparent predilection to associate with complex cardiometabolic traits.
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Doenças Cardiovasculares/genética , Doenças Metabólicas/genética , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Sintenia , Fatores de Risco Cardiometabólico , Doenças Cardiovasculares/diagnóstico , Bases de Dados Genéticas , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Hereditariedade , Humanos , Doenças Metabólicas/diagnóstico , Linhagem , Medição de RiscoRESUMO
BACKGROUND: Heart failure predisposes to intracardiac thrombus (ICT) formation. There are limited data on the prevalence and impact of preexisting ICT on postoperative outcomes in left ventricular assist device patients. We examined the risk for stroke and death in this patient population. METHODS AND RESULTS: We retrospectively studied patients who were implanted with HeartMate (HM) II or HM3 between February 2009 and March 2019. Preoperative transthoracic echocardiograms, intraoperative transesophageal echocardiograms and operative reports were reviewed to identify ICT. There were 525 patients with a left ventricular assist device (median age 60.6 years, 81.8% male, 372 HMII and 151 HM3) included in this analysis. An ICT was identified in 44 patients (8.4%). During the follow-up, 43 patients experienced a stroke and 55 died. After multivariable adjustment, presence of ICT increased the risk for the composite of stroke or death at 6-month (hazard ratio [HR] 1.82, 95% confidence interval [CI] 1.00-3.33, Pâ¯=â¯.049). Patients with ICT were also at higher risk for stroke (HR 2.45, 95% CI 1.14-5.28, Pâ¯=â¯.021) and death (HR 2.36, 95% CI 1.17-4.79 Pâ¯=â¯.016) at 6 months of follow-up. CONCLUSIONS: The presence of ICT is an independent predictor of stroke and death at 6 months after left ventricular assist device implantation. Additional studies are needed to help risk stratify and optimize the perioperative management of this patient population.
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Insuficiência Cardíaca , Coração Auxiliar , Acidente Vascular Cerebral , Trombose , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Trombose/diagnóstico por imagem , Trombose/epidemiologia , Resultado do TratamentoRESUMO
This review focuses on the human genetics, epidemiology, and molecular pathophysiology of sex differences in central obesity, adipose distribution, and related cardiometabolic disorders. Distribution of fat is important for cardiometabolic health, with peripheral fat depots having a protective effect and central visceral fat depots conferring a detrimental effect on health. There are important sex differences in fat distribution that are masked when studying body mass index as a measure of obesity. From epidemiological, murine, and in vitro studies, several mechanisms have been proposed to explain the sex differences in adipose distribution, including sex hormonal effects, cell-intrinsic properties, and the microenvironment in fat depots. More recently, human genetics have revealed hundreds of loci for central obesity providing disruptive opportunities for mechanistic discoveries and clinical translation. A striking feature is that over one-third of these loci have reproducible but poorly understood sexual dimorphic associations with central obesity, most having stronger effects in women. Understanding the genetic and molecular mechanisms of adipose distribution and its sexual dimorphism in humans provides a unique opportunity to promote the use of precision medicine for early identification of at-risk individuals, and the development of novel therapeutic strategies for central obesity and related cardiometabolic disorders.
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Tecido Adiposo/metabolismo , Doenças Cardiovasculares/genética , Genômica/métodos , Obesidade Abdominal/genética , Medicina de Precisão/métodos , Medição de Risco/métodos , Animais , Distribuição da Gordura Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Saúde Global , Humanos , Incidência , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Fatores SexuaisRESUMO
BACKGROUND: Omega-3 fatty acids from fish oil have been associated with beneficial cardiovascular effects, but their role in modifying cardiac structures and tissue characteristics in patients who have had an acute myocardial infarction while receiving current guideline-based therapy remains unknown. METHODS: In a multicenter, double-blind, placebo-controlled trial, participants presenting with an acute myocardial infarction were randomly assigned 1:1 to 6 months of high-dose omega-3 fatty acids (n=180) or placebo (n=178). Cardiac magnetic resonance imaging was used to assess cardiac structure and tissue characteristics at baseline and after study therapy. The primary study endpoint was change in left ventricular systolic volume index. Secondary endpoints included change in noninfarct myocardial fibrosis, left ventricular ejection fraction, and infarct size. RESULTS: By intention-to-treat analysis, patients randomly assigned to omega-3 fatty acids experienced a significant reduction of left ventricular systolic volume index (-5.8%, P=0.017), and noninfarct myocardial fibrosis (-5.6%, P=0.026) in comparison with placebo. Per-protocol analysis revealed that those patients who achieved the highest quartile increase in red blood cell omega-3 index experienced a 13% reduction in left ventricular systolic volume index in comparison with the lowest quartile. In addition, patients in the omega-3 fatty acid arm underwent significant reductions in serum biomarkers of systemic and vascular inflammation and myocardial fibrosis. There were no adverse events associated with high-dose omega-3 fatty acid therapy. CONCLUSIONS: Treatment of patients with acute myocardial infarction with high-dose omega-3 fatty acids was associated with reduction of adverse left ventricular remodeling, noninfarct myocardial fibrosis, and serum biomarkers of systemic inflammation beyond current guideline-based standard of care. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00729430.
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Ácidos Graxos Ômega-3/uso terapêutico , Infarto do Miocárdio/complicações , Remodelação Ventricular/efeitos dos fármacos , Idoso , Biomarcadores , Método Duplo-Cego , Ácidos Graxos Ômega-3/efeitos adversos , Ácidos Graxos Ômega-3/farmacologia , Feminino , Fibrose , Ventrículos do Coração , Humanos , Inflamação/sangue , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Náusea/virologia , Tamanho do Órgão , Estudos Prospectivos , Sístole , Resultado do Tratamento , Troponina T/sangueRESUMO
Recent advances in next generation sequencing have enabled panel gene testing, or simultaneous testing for mutations in multiple genes for a clinical condition. With more extensive and widespread genetic testing, there will be increased detection of genes with moderate penetrance without established clinical guidelines and of variants of uncertain significance (VUS), or genetic variants unknown to either be disease-causing or benign. This study surveyed 232 patients who underwent genetic counseling for hereditary breast and ovarian cancer to examine the impact of panel gene testing on psychological outcomes, patient understanding, and utilization of genetic information. The survey used standardized instruments including the Impact of Event Scale (IES), Multidimensional Impact of Cancer Risk Assessment (MICRA), Satisfaction with Decision Instrument (SWD), Ambiguity Tolerance Scale (AT-20), genetics knowledge, and utilization of genetic test results. Study results suggested that unaffected individuals with a family history of breast or ovarian cancer who received positive results were most significantly impacted by intrusive thoughts, avoidance, and distress. However, scores were also modestly elevated among unaffected patients with a family history of breast and ovarian cancer who received VUS, highlighting the impact of ambiguous results that are frequent among patients undergoing genetic testing with large panels of genes. Potential risk factors for increased genetic testing-specific distress in this study included younger age, black or African American race, Hispanic origin, lower education level, and lower genetic knowledge and highlight the need for developing strategies to provide effective counseling and education to these communities, particularly when genetic testing utilizes gene panels that more commonly return VUS. More detailed pre-test education and counseling may help patients appreciate the probability of various types of test results and how results would be used clinically, and allow them to make more informed decisions about the type of genetic testing to select.
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Neoplasias da Mama/genética , Aconselhamento Genético/organização & administração , Predisposição Genética para Doença/genética , Testes Genéticos/métodos , Neoplasias Ovarianas/genética , Adulto , Neoplasias da Mama/diagnóstico , Feminino , Aconselhamento Genético/psicologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Oncologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Fatores de RiscoRESUMO
BACKGROUND: Pulmonary nodules (PNs) are often detected incidentally during coronary computed tomographic (CT) angiography, which is increasingly being used to evaluate patients with chest pain symptoms. However, the efficiency of following up on incidentally detected PN is unknown. METHODS AND RESULTS: We determined demographic and clinical characteristics of stable symptomatic patients referred for coronary CT angiography in whom incidentally detected PNs warranted follow-up. A validated lung cancer simulation model was populated with data from these patients, and clinical and economic consequences of follow-up per Fleischner guidelines versus no follow-up were simulated. Of the 3665 patients referred for coronary CT angiography, 591 (16%) had PNs requiring follow-up. The mean age of patients with PNs was 59±10 years; 66% were male; 67% had ever smoked; and 21% had obstructive coronary artery disease. The projected overall lung cancer incidence was 5.8% in these patients, but the majority died of coronary artery disease (38%) and other causes (57%). Follow-up of PNs was associated with a 4.6% relative reduction in cumulative lung cancer mortality (absolute mortality: follow-up, 4.33% versus non-follow-up, 4.54%), more downstream testing (follow-up, 2.34 CTs per patient versus non-follow-up, 1.01 CTs per patient), and an average increase in quality-adjusted life of 7 days. Costs per quality-adjusted life-year gained were $154 700 to follow up the entire cohort and $129 800 per quality-adjusted life-year when only smokers were included. CONCLUSIONS: Follow-up of PNs incidentally detected in patients undergoing coronary CT angiography for chest pain evaluation is associated with a small reduction in lung cancer mortality. However, significant downstream testing contributes to limited efficiency, as demonstrated by a high cost per quality-adjusted life-year, especially in nonsmokers.
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Técnicas de Imagem Cardíaca/economia , Angiografia Coronária/economia , Doença da Artéria Coronariana/economia , Neoplasias Pulmonares/economia , Nódulo Pulmonar Solitário/economia , Tomografia Computadorizada por Raios X/economia , Idoso , Técnicas de Imagem Cardíaca/métodos , Dor no Peito/diagnóstico por imagem , Dor no Peito/economia , Pesquisa Comparativa da Efetividade , Simulação por Computador , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Análise Custo-Benefício , Feminino , Seguimentos , Política de Saúde/economia , Humanos , Achados Incidentais , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Encaminhamento e Consulta/economia , Medição de Risco/economia , Nódulo Pulmonar Solitário/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: We sought to evaluate the effect of application of the revised 2010 Task Force Criteria (TFC) on the prevalence of major and minor Cardiovascular Magnetic Resonance (CMR) criteria for Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) versus application of the original 1994 TFC. We also assessed the utility of MRI to identify alternative diagnoses for patients referred for ARVC evaluation. METHODS: 968 consecutive patients referred to our institution for CMR with clinical suspicion of ARVC from 1995 to 2010, were evaluated for the presence of major and minor CMR criteria per the 1994 and 2010 ARVC TFC. CMR criteria included right ventricle (RV) dilatation, reduced RV ejection fraction, RV aneurysm, or regional RV wall motion abnormalities. When quantitative measures of RV size and function were not available, and in whom abnormal size or function was reported, a repeat quantitative analysis by 2 qualified CMR physicians in consensus. RESULTS: Of 968 patients, 220 (22.7%) fulfilled either a major or a minor 1994 TFC, and 25 (2.6%) fulfilled any of the 2010 TFC criterion. Among patients meeting any 1994 criteria, only 25 (11.4%) met at least one 2010 criterion. All patients who fulfilled a 2010 criteria also satisfied at least one 1994 criterion. Per the 2010 TFC, 21 (2.2%) patients met major criteria and 4 (0.4%) patients fulfilled at least one minor criterion. Eight patients meeting 1994 minor criteria were reclassified as satisfying 2010 major criteria, while 4 patients fulfilling 1994 major criteria were reclassified to only minor or no criteria under the 2010 TFC.Eighty-nine (9.2%) patients had alternative cardiac diagnoses, including 43 (4.4%) with clinically significant potential ARVC mimics. These included cardiac sarcoidosis, RV volume overload conditions, and other cardiomyopathies. CONCLUSIONS: Application of the 2010 TFC resulted in reduction of total patients meeting any diagnostic CMR criteria for ARVC from 22.7% to 2.6% versus the 1994 TFC. CMR identified alternative cardiac diagnoses in 9.2% of patients, and 4.4% of the diagnoses were potential mimics of ARVC.
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Displasia Arritmogênica Ventricular Direita/diagnóstico , Ventrículos do Coração/patologia , Imageamento por Ressonância Magnética/normas , Miocárdio/patologia , Adulto , Displasia Arritmogênica Ventricular Direita/classificação , Displasia Arritmogênica Ventricular Direita/epidemiologia , Displasia Arritmogênica Ventricular Direita/patologia , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Meios de Contraste , Diagnóstico Diferencial , Feminino , Fidelidade a Diretrizes , Ventrículos do Coração/fisiopatologia , Humanos , Hipertrofia Ventricular Direita/diagnóstico , Hipertrofia Ventricular Direita/epidemiologia , Hipertrofia Ventricular Direita/patologia , Masculino , Pessoa de Meia-Idade , Contração Miocárdica , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Prevalência , Estudos Retrospectivos , Volume Sistólico , Disfunção Ventricular Direita/diagnóstico , Disfunção Ventricular Direita/epidemiologia , Disfunção Ventricular Direita/patologia , Função Ventricular DireitaRESUMO
BACKGROUND: Omega-3 polyunsaturated fatty acids (O3-FA) have been shown to reduce inflammation and adverse cardiac remodeling after acute myocardial infarction (AMI). However, the impact of O3-FA on long-term clinical outcomes remains uncertain. AIMS: To investigate the impact of O3-FA on adverse cardiac events in long-term follow up post AMI in a pilot-study. METHODS: Consecutive patients with AMI were randomized 1:1 to receive 6 months of O3-FA (4 g/daily) or placebo in the prospective, multicenter OMEGA-REMODEL trial. Primary endpoint was a composite of major adverse cardiovascular events (MACE) encompassing all-cause death, heart failure hospitalizations, recurrent acute coronary syndrome, and late coronary artery bypass graft (CABG). RESULTS: A total of 358 patients (62.8% male; 48.1 ± 16.1 years) were followed for a median of 6.6 (IQR: 5.0-9.1) years. Among those receiving O3-FA (n = 180), MACE occurred in 65 (36.1%) compared to 62 (34.8%) of 178 assigned to placebo. By intention-to-treat analysis, O3-FA treatment assignment did not reduce MACE (HR = 1.014; 95%CI = 0.716-1.436; p = 0.938), or its individual components. However, patients with a positive response to O3-FA treatment (n = 43), defined as an increase in the red blood cell omega-3 index (O3I) ≥5% after 6 months of treatment, had lower annualized MACE rates compared to those without (2.9% (95%CI = 1.2-5.1) vs 7.1% (95%CI = 5.7-8.9); p = 0.001). This treatment benefit persisted after adjustment for baseline characteristics (HRadjusted = 0.460; 95%CI = 0.218-0.970; p = 0.041). CONCLUSION: In long-term follow-up of the OMEGA-REMODEL randomized trial, O3-FA did not reduce MACE after AMI by intention to treat principle, however, patients who achieved a ≥ 5% increase of O3I subsequent to treatment had favorable outcomes.
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Síndrome Coronariana Aguda , Ácidos Graxos Ômega-3 , Infarto do Miocárdio , Feminino , Humanos , Masculino , Síndrome Coronariana Aguda/tratamento farmacológico , Ácido Eicosapentaenoico , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/induzido quimicamente , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento , Adulto , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Heart failure (HF) is one of the most common and lifestyle-limiting complications of hypertrophic cardiomyopathy (HCM). Prediction of worsening HF using clinical measures alone remains limited. Moreover, the mechanisms by which patients with HCM develop worsening HF have not been elucidated. Therefore, the aim of this study was to develop a plasma proteomics-based model to predict worsening HF among patients with HCM and to identify signalling pathways that are differentially regulated in those who subsequently develop worsening HF. METHODS: In this multi-centre, prospective cohort study of 389 patients with HCM, plasma proteomics profiling of 4986 proteins was performed at enrolment. A proteomics-based random forest model was developed to predict worsening HF using data from one institution (training set, n=268). This model was externally validated in patients from a different institution (test set, n=121). Pathway analysis of proteins significantly dysregulated in patients who subsequently developed worsening HF compared with those who did not was executed, using a false discovery rate (FDR) threshold of <0.001. RESULTS: Using the 11-protein proteomics-based model derived from the training set, the area under the receiver-operating characteristic curve to predict worsening HF was 0.87 (95% CI: 0.76 to 0.98) in the test set. Pathway analysis revealed that the Ras-MAPK pathway (FDR<0.00001) and related pathways were dysregulated in patients who subsequently developed worsening HF. CONCLUSIONS: The present study with comprehensive plasma proteomics profiling demonstrated a high accuracy to predict worsening HF in patients with HCM and identified the Ras-MAPK and related signalling pathways as potential underlying mechanisms.
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Cardiomiopatia Hipertrófica , Insuficiência Cardíaca , Humanos , Estudos Prospectivos , Proteômica , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/complicações , Transdução de SinaisRESUMO
Hypertrophic cardiomyopathy (HCM) is most commonly associated with obstructive symptoms and sudden cardiac death; however, predominantly nonobstructive advanced heart failure in HCM, marked by medically refractory disease with severe functional impairment, occurs in 5% to 7% of patients with HCM. The diagnosis relies on the integration of imaging (echocardiography/cardiac magnetic resonance), hemodynamic data, and cardiopulmonary exercise testing to identify the patients who will benefit from advanced heart failure therapies. Most advanced heart failure therapies focus on systolic dysfunction and are not always applicable to this patient population. Left ventricular assist devices may be an option in a highly selected population with left ventricular dilation. Heart transplantation is often the best option for patients with advanced heart failure in HCM with excellent post-transplantation survival.
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Cardiomiopatia Hipertrófica , Insuficiência Cardíaca , Transplante de Coração , Humanos , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/diagnóstico , Cardiomiopatia Hipertrófica/terapia , Cardiomiopatia Hipertrófica/complicações , Ecocardiografia , Teste de EsforçoRESUMO
Background: Pulmonary embolism (PE) outcomes are determined by presentation severity and host-related factors. Limited data exist regarding the association of modified body mass index (mBMI), used as a frailty surrogate, with clinical outcomes after treatment for PE. Therefore, we sought to determine the association of mBMI with mortality and bleeding after treatment for intermediate or high-risk PE. Methods: Patients treated for intermediate-risk or high-risk PE at a large academic center between 2013 and 2019 were studied. PE was characterized as intermediate risk (right ventricular compromise) or high risk (hemodynamic compromise) per European Society of Cardiology guidelines. mBMI was defined as the product of serum albumin concentration and body mass index. Patients were stratified according to mBMI quartiles, with low mBMI defined as ≤79, and evaluated for primary end points of in-hospital mortality and bleeding after treatment. A multivariable logistic regression analysis was performed for primary end points. Results: A total of 843 patients were treated for PE. Low mBMI was associated with increased burden of comorbidities and lower rates of interventional or surgical treatment. mBMI was independently associated with mortality (Q1, 22.8%; Q2, 12.4%; Q3, 10.9%; Q4, 6.6%; P = .005) and bleeding (Q1, 20.1%; Q2, 10.1%; Q3, 13.3%; Q4, 11.0%; P = .006). Compared with the lowest mBMI quartile, the highest mBMI quartile was independently associated with lower rates of mortality (OR, 0.28; 95% CI, 0.13-0.58; P < .001) and bleeding (OR, 0.42; 95% CI, 0.23-0.76; P = .004). Conclusions: Low mBMI is prevalent in patients with intermediate-risk and high-risk PE and is independently associated with in-hospital mortality and bleeding after treatment.
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Background: Studies examining outcomes among individuals with COronaVIrus Disease 2019 (COVID-19) have consistently demonstrated that men have worse outcomes than women, with a higher incidence of myocardial injury, respiratory failure, and death. However, mechanisms of higher morbidity and mortality among men remain poorly understood. We aimed to identify mediators of the relationship between sex and COVID-19-associated mortality. Methods: Patients hospitalized at two quaternary care facilities, New York Presbyterian Hospital (CUIMC/NYPH) and Massachusetts General Hospital (MGH), for SARS-CoV-2 infection between February and May 2020 were included. Five independent biomarkers were identified as mediators of sex effects, including high-sensitivity cardiac troponin T (hs-cTNT), high sensitivity C-reactive protein (hs-CRP), ferritin, D-dimer, and creatinine. Results: In the CUIMC/NYPH cohort (n = 2,626, 43% female), male sex was associated with significantly greater mortality (26 vs. 21%, p = 0.0146) and higher peak hs-cTNT, hs-CRP, ferritin, D-dimer, and creatinine (p < 0.001). The effect of male sex on the primary outcome of death was partially mediated by peak values of all five biomarkers, suggesting that each pathophysiological pathway may contribute to increased risk of death in men. Hs-cTnT, creatinine, and hs-CRP were the strongest mediators. Findings were highly consistent in the MGH cohort with the exception of D-dimer. Conclusions: This study suggests that the effect of sex on COVID-19 outcomes is mediated by cardiac and kidney injury, as well as underlying differences in inflammation and iron metabolism. Exploration of these specific pathways may facilitate sex-directed diagnostic and therapeutic strategies for patients with COVID-19 and provides a framework for the study of sex differences in other complex diseases.
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Driveline infection (DLI) is common after left ventricular assist device (LVAD). Limited data exist on DLI prevention and management. We investigated the impact of standardized driveline care initiatives, specific pathogens, and chronic antibiotic suppression (CAS) on DLI outcomes. 591 LVAD patients were retrospectively categorized based on driveline care initiatives implemented at our institution (2009-2019). Era (E)1: nonstandardized care; E2: standardized driveline care protocol; E3: addition of marking driveline exit site; E4: addition of "no shower" policy. 87(15%) patients developed DLI at a median (IQR) of 403(520) days. S. aureus and P. aeruginosa were the most common pathogens. 31 (36%) of DLI patients required incision and drainage (I&D) and 5 (5.7%) device exchange. P. aeruginosa significantly increased risk for initial I&D (HR 2.7, 95% CI, 1.1-6.3) and recurrent I&D or death (HR 4.2, 95% CI, 1.4-12.5). Initial I&D was associated with a significant increased risk of death (HR 2.92 (1.33-6.44); P = 0.008) when compared to patients who did not develop DLI. Implementation of standardized driveline care protocol (E2) was associated with increased 2-year freedom from DLI compared to nonstandardized care (HR 0.36, 95% CI, 0.2-0.6, P < 0.01). Additional preventive strategies (E3&E4) showed no further reduction in DLI rates. 57(65%) DLI patients received CAS, 44% of them required escalation to intravenous antibiotics and/or I&D. Presence of P. aeruginosa DLI markedly increased risk for I&D or death. Conditional survival of patients progressing to I&D is diminished. Standardized driveline care protocol was associated with a significant reduction in DLI, while additional preventive strategies require further testing.
Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Infecções Relacionadas à Prótese , Humanos , Coração Auxiliar/efeitos adversos , Estudos Retrospectivos , Staphylococcus aureus , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/etiologia , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/prevenção & controleRESUMO
BACKGROUND: Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood. OBJECTIVE: To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes. METHODS: This hospital-based, observational study included 3828 SARS-CoV-2-infected patients who were hospitalized February to May 2020 at Massachusetts General Hospital (MGH) or Columbia University Irving Medical Center/New York Presbyterian Hospital (CUIMC/NYP). We use mediation analysis to evaluate whether peak inflammatory biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], D-dimer, ferritin, white blood cell count and interleukin-6) are in the causal pathway between obesity (BMI ≥ 30) and mechanical ventilation or death within 28 days of presentation to care. RESULTS: In the MGH cohort (n = 1202), obesity was associated with greater likelihood of ventilation or death (ORâ =â 1.73; 95% CIâ =â [1.25, 2.41]; Pâ =â 0.001) and higher peak CRP (Pâ <â 0.001) compared with nonobese patients. The estimated proportion of the association between obesity and ventilation or death mediated by CRP was 0.49 (Pâ <â 0.001). Evidence of mediation was more pronounced in patientsâ <â 65 years (proportion mediatedâ =â 0.52 [Pâ <â 0.001] vs 0.44 [Pâ =â 0.180]). Findings were more moderate but consistent for peak ESR. Mediation by other inflammatory markers was not supported. Results were replicated in CUIMC/NYP cohort (nâ =â 2626). CONCLUSION: Findings support systemic inflammatory pathways in obesity-associated severe COVID-19 disease, particularly in patientsâ <â 65 years, captured by CRP and ESR. Contextualized in clinical trial findings, these results reveal therapeutic opportunity to target systemic inflammatory pathways and monitor interventions in high-risk subgroups and particularly obese patients.
Assuntos
COVID-19/complicações , Obesidade/complicações , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Sedimentação Sanguínea , Proteína C-Reativa/análise , COVID-19/mortalidade , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Interleucina-6/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Obesidade/mortalidade , Fatores de Risco , Síndrome de Resposta Inflamatória Sistêmica/mortalidade , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
AIMS: We aimed to detail the early clinical experience with pVAD 5.5 at a large academic medical centre. Impella® 5.5 (Abiomed) is a temporary peripherally inserted left ventricular assist device (pVAD) used for the treatment of cardiogenic shock (CS). This system has several modifications aimed at improving deliverability and durability over the pVAD 5.0 system, but real-world experience with this device remains limited. METHODS AND RESULTS: We collected clinical and outcome data on all patients supported with pVAD 5.5 at our centre between February and December 2020, including procedural and device-related complications. Fourteen patients with pVAD 5.5 were included. Aetiology of CS was acute myocardial infarction (n = 6), decompensated heart failure (n = 6), suspected myocarditis (n = 1), and post-cardiotomy CS (n = 1). Four patients received pVAD 5.5 after being on inotropes alone, two were escalated from intra-aortic balloon pump, two were escalated from pVAD CP, and six patients were transitioned to pVAD 5.5 from extracorporeal membrane oxygenation. Median duration of pVAD 5.5 support was 12 (interquartile range 7, 25) days. Complications included axillary insertion site haematoma (n = 3), acute kidney injury (n = 3), severe thrombocytopenia (n = 1), and stroke (n = 1). No valve injury or limb complications occurred. Survival to device explant for recovery or transition to another therapy was 11/14 (79%) patients. CONCLUSIONS: In this early experience of the pVAD 5.5, procedural and device-related complications were observed but were manageable, and overall survival was high in this critically ill cohort, particularly when the device was used as a bridge to other therapies.
Assuntos
Coração Auxiliar , Choque Cardiogênico , Humanos , Balão Intra-Aórtico , Estudos Retrospectivos , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Centros de Atenção Terciária , Resultado do TratamentoRESUMO
AIMS: Infections are common following left ventricular assist device (LVAD) implantation and predict adverse events. Infections are frequent prior to LVAD implantation although their impact on postoperative outcomes remains unknown. Gut and nasal microbial imbalance may predispose to mucosal colonization with pathogens. Herein, we investigated the predictive role of pre-LVAD infections, and explored the association of nasal Staphylococcus aureus (SA) colonization and gut microbiota, on postoperative outcomes. METHODS AND RESULTS: Overall, 254 LVAD patients were retrospectively categorized based on pre-LVAD infection status: Group 1, bacterial/fungal bloodstream infection (BSI); Group 2, other bacterial/fungal; Group 3, viral; and Group 4, no infection. In a subset of patients, nasal SA colonization (n = 140) and pre-LVAD stool (n = 25) were analysed using 16S rRNA sequencing. A total of 75 (29%) patients had a pre-LVAD infection [Group 1: 22 (29%); Group 2: 41 (55%); Group 3: 12 (16%)]. Pre-LVAD BSIs were independent predictors of 1-year postoperative mortality and infections [Group 1 vs. 4: hazard ratio (HR) 2.70, P = 0.036 vs. HR 1.8, P = 0.046]. In an unadjusted analysis, pre-LVAD infections other than BSIs, INTERMACS profile ≤2, higher serum creatinine, lower serum albumin and nasal SA colonization were also significantly associated with postoperative infections. Patients with early post-LVAD infections exhibited decreased microbial diversity (P < 0.05). CONCLUSIONS: Pre-LVAD infections are common. BSIs independently predict postoperative mortality and infections. Additional studies are needed to confirm our findings that pre-LVAD SA nasal colonization and gut microbial composition can help stratify patients' risk for infectious complications after LVAD implantation.