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BACKGROUND: The impact of the COVID-19 pandemic on palliative care intervention (PCIs) in patients with do-not-resuscitate (DNR) status remains uncertain. METHODS: Case-control study of patients with DNR order with RT-PCR confirmed SARS-COV2 infection (cases), and those with DNR order but without SARS-COV2 infection (controls). The primary outcome measures included timing and delivery of PCIs, and secondary measures included pre-admission characteristics and in-hospital death. RESULTS: The ethnicity distribution was comparable between 69 cases and 138 controls, including Black/African Americans (61% vs. 44%), Latino/Hispanics (16% vs. 26%) and White (9% vs. 20%) (trend-p = .54). Cases were employed more (17% vs. 6%, adjusted-p = .012), less frail (fit 47% vs. 21%; mildly frail 22% vs. 36%; frail 31% vs. 43%, trend-p = .018) and had fewer comorbidities than controls. Cases had higher chances of intensive care unit admission (HR 1.76 [95% CI: 1.03-3.02]) and intubation (53% vs. 30%, p = .002), lower chances to be seen by palliative care team (HR .46 [.30-.70]) and a longer time to palliative care visit than controls (ß per ln-day .67 [.00-1.34]). In the setting of no-visiting hospitals policy, we did not find significant increase in utilisation of video conferencing (22% vs. 13%) and religious services (12% vs. 12%) both in case and in controls. CONCLUSION: Do-not-resuscitate patients with COVID-19 had better general health and higher employment status than 'typical' DNR patients, but lower chances to be seen by the palliative care team. This study raises a question of the applicability of the current palliative care model in addressing the needs of DNR patients with COVID-19 during the pandemic.
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COVID-19 , Cuidados Paliativos , Humanos , Mortalidade Hospitalar , Pandemias , COVID-19/epidemiologia , Estudos de Casos e Controles , RNA Viral , SARS-CoV-2 , Estudos RetrospectivosRESUMO
PURPOSE OF REVIEW: Transcatheter valve therapies for mitral and tricuspid regurgitation are alternative methods to more invasive surgical treatment in candidates with high or prohibitive surgical risk. Echocardiography is the primary imaging modality for patient selection, pre-procedural planning, intra-procedural guidance, and post-procedural follow-up. RECENT FINDINGS: This article outlines the applications of transcatheter valve repair therapy for mitral and tricuspid regurgitation based on the current cardiovascular guidelines and a growing body of evidence. In this review, we provide a stepwise approach echocardiography in the guidance of the MitraClip device as currently the only FDA-approved transcatheter edge-to-edge repair device.
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Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Insuficiência da Valva Tricúspide , Humanos , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/cirurgia , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Ecocardiografia Transesofagiana/métodos , Ecocardiografia/métodos , Implante de Prótese de Valva Cardíaca/métodos , Cateterismo Cardíaco/métodos , Resultado do TratamentoRESUMO
Objectives Details of the biological variability of high-sensitivity C-reactive protein (hs-CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and ST2 are currently lacking in patients with acute coronary syndrome (ACS) but are crucial knowledge when aiming to use these biomarkers for personalized risk prediction. In the current study, we report post-ACS kinetics and the variability of the hs-CRP, NT-proBNP and ST2. Methods BIOMArCS is a prospective, observational study with high frequency blood sampling during 1 year post-ACS. Using 1507 blood samples from 191 patients that remained free from adverse cardiac events, we investigated post-ACS kinetics of hs-CRP, NT-proBNP and ST2. Biological variability was studied using the samples collected between 6 and 12 months after the index ACS, when patients were considered to have stable coronary artery disease. Results On average, hs-CRP rose peaked at day 2 and rose well above the reference value. ST2 peaked immediately after the ACS but never rose above the reference value. NT-proBNP level rose on average during the first 2 days post-ACS and slowly declined afterwards. The within-subject variation and relative change value (RCV) of ST2 were relatively small (13.8%, RCV 39.7%), while hs-CRP (41.9%, lognormal RCV 206.1/-67.3%) and NT-proBNP (39.0%, lognormal RCV 185.2/-64.9%) showed a considerable variation. Conclusions Variability of hs-CRP and NT-proBNP within asymptomatic and clinically stable post-ACS patients is considerable. In contrast, within-patient variability of ST2 is low. Given the low within-subject variation, ST2 might be the most useful biomarker for personalizing risk prediction in stable post-ACS patients.
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Síndrome Coronariana Aguda/metabolismo , Síndrome Coronariana Aguda/sangue , Adulto , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , Doença da Artéria Coronariana/sangue , Feminino , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/análise , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Peptídeo Natriurético Encefálico/análise , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: When the treatment effect on the outcome of interest is influenced by a baseline/demographic factor, investigators say that an interaction is present. In randomized clinical trials (RCTs), this type of analysis is typically referred to as subgroup analysis. Although interaction (or subgroup) analyses are usually stated as a secondary study objective, it is not uncommon that these results lead to changes in treatment protocols or even modify public health policies. Nonetheless, recent reviews have indicated that their proper assessment, interpretation and reporting remain challenging. RESULTS: Therefore, this article provides an overview of these challenges, to help investigators find the best strategy for application of interaction analyses on binary outcomes in RCTs. Specifically, we discuss the key points of formal interaction testing, including the estimation of both additive and multiplicative interaction effects. We also provide recommendations that, if adhered to, could increase the clarity and the completeness of reports of RCTs. CONCLUSION: Altogether, this article provides a brief non-statistical guide for clinical investigators on how to perform, interpret and report interaction (subgroup) analyses in RCTs.
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Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Interpretação Estatística de Dados , Humanos , Modelos EstatísticosRESUMO
In nephrology, repeated measures are frequently available (glomerular filtration rate or proteinuria) and linked to adverse outcomes. However, several features of these longitudinal data should be considered before making such inferences. These considerations are discussed, and we describe how joint modeling of repeatedly measured and time-to-event data may help to assess disease dynamics and to derive personalized prognosis. Joint modeling combines linear mixed-effects models and Cox regression model to relate patient-specific trajectory to their prognosis. We describe several aspects of the relationship between time-varying markers and the endpoint of interest that are assessed with real examples to illustrate the aforementioned aspects of the longitudinal data provided. Thus, joint models are valuable statistical tools for study purposes but also may help health care providers in making well-informed dynamic medical decisions.
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Tomada de Decisão Clínica/métodos , Nefropatias/diagnóstico , Modelos Biológicos , Nefrologia/métodos , Taxa de Filtração Glomerular , Humanos , Prognóstico , Análise de Regressão , Medição de Risco/métodosRESUMO
Renal dysfunction is an important component of chronic heart failure (CHF), but its single assessment does not sufficiently reflect clinically silent progression of CHF prior to adverse clinical outcome. Therefore, we aimed to investigate temporal evolutions of glomerular and tubular markers in 263 stable patients with CHF, and to determine if their patient-specific evolutions during this clinically silent period can dynamically predict clinical outcome. We determined the risk of clinical outcome (composite endpoint of Heart Failure hospitalization, cardiac death, Left Ventricular Assist Device placement, and heart transplantation) in relation to marker levels, slopes and areas under their trajectories. In each patient, the trajectories were estimated using repeatedly measured glomerular markers: creatinine/estimated glomerular filtration rate (eGFR), cystatin C (CysC), and tubular markers: urinary N-acetyl-beta-D-glucosaminidase (NAG) and kidney injury molecule (KIM)-1, plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL). During 2.2 years of follow-up, we collected on average 8 urine and 9 plasma samples per patient. All glomerular markers predicted the endpoint (univariable hazard ratio [95% confidence interval] per 20% increase: creatinine: 1.18[1.07-1.31], CysC: 2.41[1.81-3.41], and per 20% eGFR decrease: 1.13[1.05-1.23]). Tubular markers, NAG, and KIM-1 also predicted the endpoint (NAG: 1.06[1.01-1.11] and KIM-1: 1.08[1.04-1.11]). Larger slopes were the strongest predictors (creatinine: 1.57[1.39-1.84], CysC: 1.76[1.52-2.09], eGFR: 1.59[1.37-1.90], NAG: 1.26[1.11-1.44], and KIM-1: 1.64[1.38-2.05]). Associations persisted after multivariable adjustment for clinical characteristics. Thus, during clinically silent progression of CHF, glomerular and tubular functions deteriorate, but not simultaneously. Hence, patient-specific evolutions of these renal markers dynamically predict clinical outcome in patients with CHF.
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Taxa de Filtração Glomerular , Insuficiência Cardíaca/fisiopatologia , Nefropatias/fisiopatologia , Rim/fisiopatologia , Volume Sistólico , Função Ventricular Esquerda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/urina , Causas de Morte , Progressão da Doença , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Transplante de Coração , Coração Auxiliar , Hospitalização , Humanos , Nefropatias/diagnóstico , Nefropatias/mortalidade , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Países Baixos , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE OF REVIEW: The purpose of this study was to investigate the association of 26 inflammatory biomarkers (acute phase proteins, cytokines, chemokines) and renal markers with coronary lipid core burden index (LCBI) assessed by near-infrared spectroscopy (NIRS) imaging, as well as the association of these biomarkers with long-term cardiovascular outcome. RECENT FINDINGS: NIRS-derived LCBI has recently been shown to be an independent predictor of major adverse cardiac events (MACE). However, studies on the association between circulating biomarkers and NIRS-derived characteristics have not yet been performed. Between 2008 and 2011, 581 patients underwent diagnostic coronary angiography or percutaneous coronary intervention for stable angina pectoris or acute coronary syndrome (ACS). NIRS of a non-culprit vessel was performed in a subset of 203 patients. In multivariable analyses, TNF-α tended to be associated with higher LCBI (beta 0.088 ln (pg/ml) increase per unit LCBI; 95% CI 0.000-0.177, p = 0.05) after adjustment for clinical characteristics. However, this association did not persist after Bonferroni correction (statistical threshold 0.0019). Major adverse cardiac events (MACE) were registered in 581 patients during a median follow-up time of 4.7 years (IQR: [4.2-5.6] years). After adjustment for clinical characteristics and Bonferroni correction, IL-8 (HR 1.60; 95% CI [1.18-2.17] per ln (pg/ml), p = 0.002) was borderline associated with MACE and significantly associated with all-cause mortality or ACS (HR 1.75; 95% CI [1.24-2.48] per ln (pg/ml), p = 0.0015). In conclusion, we found that IL-8 was independently associated with clinical outcome, but altogether, the multiplex panel we investigated here did not render a useful blood biomarker of high LCBI.
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Biomarcadores/sangue , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho , Síndrome Coronariana Aguda/terapia , Proteínas de Fase Aguda/análise , Adiponectina/sangue , Angina Estável/terapia , Creatinina/análise , Cistatina C/análise , Citocinas/sangue , Humanos , Lipocalina-2/análise , Infarto do Miocárdio/epidemiologia , Mioglobina/sangue , Intervenção Coronária Percutânea , Acidente Vascular Cerebral/epidemiologia , Microglobulina beta-2/sangueRESUMO
Although both internal iliac arteries were saved during operation, the patient developed paraplegia immediately after aortoiliac reconstruction due to the spinal cord ischemia. We report a successfully treated immediate postoperative paraplegia by performing second operation and creating bypass from the bifurcated Dacron graft to the previously detected nonpaired huge lumbar artery.
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Aneurisma da Aorta Abdominal/cirurgia , Artérias/cirurgia , Implante de Prótese Vascular/efeitos adversos , Aneurisma Ilíaco/cirurgia , Paraplegia/cirurgia , Isquemia do Cordão Espinal/cirurgia , Medula Espinal/irrigação sanguínea , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/fisiopatologia , Artérias/fisiopatologia , Prótese Vascular , Implante de Prótese Vascular/instrumentação , Angiografia por Tomografia Computadorizada , Humanos , Aneurisma Ilíaco/diagnóstico por imagem , Aneurisma Ilíaco/fisiopatologia , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Paraplegia/diagnóstico , Paraplegia/fisiopatologia , Polietilenotereftalatos , Desenho de Prótese , Fluxo Sanguíneo Regional , Reoperação , Isquemia do Cordão Espinal/diagnóstico por imagem , Isquemia do Cordão Espinal/etiologia , Isquemia do Cordão Espinal/fisiopatologia , Resultado do TratamentoRESUMO
We report an unusual case of aneurysm of the left common iliac vein and thrombus formation in inferior vena cava associated with Parkes Weber syndrome (PWS). In addition to many already known clinical signs which determine PWS, common iliac vein aneurysm formation together with inferior vena cava thrombus present a new clinical feature and new challenges in treatment strategy of these patients.
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Aneurisma/etiologia , Veia Ilíaca , Síndrome de Sturge-Weber/complicações , Veia Cava Inferior , Trombose Venosa/etiologia , Aneurisma/diagnóstico , Aneurisma/terapia , Anticoagulantes/uso terapêutico , Feminino , Humanos , Veia Ilíaca/diagnóstico por imagem , Flebografia/métodos , Meias de Compressão , Síndrome de Sturge-Weber/diagnóstico , Síndrome de Sturge-Weber/terapia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Veia Cava Inferior/diagnóstico por imagem , Trombose Venosa/diagnóstico , Trombose Venosa/terapia , Adulto JovemRESUMO
We aimed to systematically analyze the literature on the use of transcatheter aortic valve replacement (TAVR) to treat active aortic valve infective endocarditis (AV-IE). Surgery is declined in one-third of patients with IE who meet indications because of prohibitive surgical risk. TAVR might be an alternative for selected patients with AV-IE as a bridge-to-surgery or stand-alone therapy. PubMed/MEDLINE, Embase, and Cochrane databases were searched (2002-2022) for studies on TAVR use in active AV-IE. Of 450 identified reports, six met inclusion criteria (all men, mean age 71 ± 12 years, median Society of Thoracic Surgeons (STS) score 27, EuroSCORE 56). All patients were prohibitive surgical risk candidates. Five out of six patients had severe, and one patient had moderate aortic regurgitation on presentation. Five out of six patients had prosthetic valve endocarditis after surgical valve replacement 13 years before (median), and one patient had TAVR a year before hospitalization. All patients had cardiogenic shock as the indication for TAVR. Four patients received balloon-expanding, and two patients received self-expanding TAVR after a median of 19 (IQR 9-25) days from diagnosis of IE. No death or myocardial infarction occurred, but one patient had a stroke within the first 30 days. The median event-free time was 9 (IQR 6-14) months including no death, reinfection, relapse IE, or valve-related rehospitalization. Our review suggests that TAVR can be considered as an adjuvant therapy to medical treatment for selected patients in whom surgery is indicated for treatment of acute heart failure due to aortic valve destruction and incompetence caused by infective endocarditis, but who have a prohibitive surgical risk. Nonetheless, a well-designed prospective registry is urgently needed to investigate the outcomes of TAVR for this off-label indication. No evidence exists for using the TAVR to treat infection-related surgical indications such as uncontrolled infection or control of septic embolization.
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Understanding the interaction between the heart and liver is pivotal for managing patients in whom both organs are affected. Studies have shown that cardio-hepatic interactions are bidirectional and that their identification, assessment, and treatment remain challenging. Congestive hepatopathy is a condition that develops in the setting of long-standing systemic venous congestion. If left untreated, congestive hepatopathy may lead to hepatic fibrosis. Acute cardiogenic liver injury develops as a combination of venous stasis and sudden arterial hypoperfusion due to cardiac, circulatory, or pulmonary failure. The treatment of both conditions should be directed toward optimizing the cardiac substrate. Hyperdynamic syndrome may develop in patients with advanced liver disease and lead to multiorgan failure. Cirrhotic cardiomyopathy or abnormalities in pulmonary vasculature, such as hepatopulmonary syndrome and portopulmonary hypertension may also develop. Each complication has unique treatment challenges and implications for liver transplantation. The presence of atrial fibrillation and atherosclerosis in liver disease brings another layer of complexity, particularly in terms of anticoagulation and statin use. This article provides an overview of cardiac syndromes in liver disease, focusing on current treatment options and future perspectives.
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A 74-year-old man with a history of bioprosthetic aortic valve replacement presented with acute severe aortic insufficiency and cardiogenic shock secondary to Diphtheroides and Enterococcus endocarditis. The patient was deemed to be not a surgical candidate by the multidisciplinary team and underwent rescue transcatheter aortic valve-in-valve replacement, resulting in complete recovery. (Level of Difficulty: Advanced.).
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We present a case of polymicrobial sepsis with Capnocytophaga spp. complicated by purpura fulminans following a dog-bite in a 50-year-old-man with an extensive history of opioid use disorder. Generally, severe Capnocytophaga cases are thought to occur in patients with underlying immune deficiencies. However, this case highlights the importance of maintaining clinical suspicion for Capnocytophaga infection in immunocompetent patients, and we discuss the role of chronic opioid-use in severe infection.
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BACKGROUND: It is uncertain that chronic heart failure (CHF) patients are susceptible to renal tubular damage with that of worsening renal function (WRF) preceding clinical outcomes. HYPOTHESIS: Changes in tubular damage biomarkers are stronger predictors of subsequent clinical events than changes in creatinine (Cr), and both have different clinical determinants. METHODS: During 2.2 years, we repeatedly simultaneously collected a median of 9 blood and 8 urine samples per patient in 263 CHF patients. We determined the slopes (rates of change) of the biomarker trajectories for plasma (Cr) and urinary tubular damage biomarkers N-acetyl-ß-d-glucosaminidase (NAG), and kidney-injury-molecule (KIM)-1. The degree of tubular injury was ranked according to NAG and KIM-1 slopes: increase in neither, increase in either, or increase in both; WRF was defined as increasing Cr slope. The composite endpoint comprised HF-hospitalization, cardiac death, left ventricular assist device placement, and heart transplantation. RESULTS: Higher baseline NT-proBNP and lower eGFR predicted more severe tubular damage (adjusted odds ratio, adj. OR [95%CI, 95% confidence interval] per doubling NT-proBNP: 1.26 [1.07-1.49]; per 10 mL/min/1.73 m2 eGFR decrease 1.16 [1.03-1.31]). Higher loop diuretic doses, lower aldosterone antagonist doses, and higher eGFR predicted WRF (furosemide per 40 mg increase: 1.32 [1.08-1.62]; spironolactone per 25 mg decrease: 1.76 [1.07-2.89]; per 10 mL/min/1.73 m2 eGFR increase: 1.40 [1.20-1.63]). WRF and higher rank of tubular injury individually entailed higher risk of the composite endpoint (adjusted hazard ratios, adj. HR [95%CI]: WRF 1.9 [1.1-3.4], tubular 8.4 [2.6-27.9]; when combined risk was highest 15.0 [2.0-111.0]). CONCLUSION: Slopes of tubular damage and WRF biomarkers had different clinical determinants. Both predicted clinical outcome, but this association was stronger for tubular injury. Prognostic effects of both appeared independent and additive.
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Taxa de Filtração Glomerular/fisiologia , Insuficiência Cardíaca/complicações , Túbulos Renais/fisiopatologia , Insuficiência Renal/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/urina , Creatinina/sangue , Creatinina/urina , Feminino , Seguimentos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Insuficiência Renal/sangue , Insuficiência Renal/etiologiaRESUMO
BACKGROUND: Impaired renal function predicts mortality in acute coronary syndrome (ACS), but its evolution immediately following index ACS and preceding next ACS has not been described in detail. We aimed to describe this evolution using serial measurements of creatinine, glomerular filtration rate [eGFRCr] and cystatin C [CysC]. METHODS: From 844 ACS patients included in the BIOMArCS study, we analysed patient-specific longitudinal marker trajectories from the case-cohort of 187 patients to determine the risk of the endpoint (cardiovascular death or hospitalization for recurrent non-fatal ACS) during 1-year follow-up. Study included only patients with eGFRCrâ¯≥â¯30â¯ml/min/1.73â¯m2. Survival analyses were adjusted for GRACE risk score and based on data >30â¯days after the index ACS (mean of 8 sample per patient). RESULTS: Mean age was 63â¯years, 79% were men, 43% had STEMI, and 67% were in eGFR stages 2-3. During hospitalization for index ACS (median [IQR] duration: 5 (3-7) days), CysC levels indicated deterioration of renal function earlier than creatinine did (CysC peaked on day 3, versus day 6 for creatinine), and both stabilized after two weeks. Higher CysC levels, but not creatinine, predicted the endpoint independently of the GRACE score within the first year after index ACS (adjusted HR [95% CI] per 1SD increase: 1.68 [1.03-2.74]). CONCLUSION: Immediately following index ACS, plasma CysC levels deteriorate earlier than creatinine-based indices do, but neither marker stabilizes during hospitalization but on average two weeks after ACS. Serially measured CysC levels predict mortality or recurrence of ACS during 1-year follow-up independently of patients' GRACE risk score.
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Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Creatinina/sangue , Cistatina C/sangue , Rim/fisiologia , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos ProspectivosRESUMO
BACKGROUND: Our aim was to explore potential use of temporal profiles of seven emerging cardio-renal and two pulmonary candidate biomarkers for predicting future adverse clinical outcome in stable patients with chronic heart failure (CHF). METHODS: In 263 CHF patients, we determined the risk of a composite endpoint of HF-hospitalization, cardiac death, LVAD-placement and heart transplantation in relation to repeatedly assessed (567 samples in total) blood biomarker levels, and slopes of their temporal trajectories (i.e., rate of biomarker change per year). In each patient, we estimated biomarker trajectories using repeatedly measured osteopontin (OPN), osteoprotegerin (OPG), epidermal growth factor receptor (EGFR), heparin-binding protein (HBP), trefoil factor-3 (TFF3), kallikrein-6 (KLK-6), matrix extracellular phosphoglycoprotein (MEPE), pulmonary surfactant-associated protein-D (PSP-D), and secretoglobulin family 3A-member-2 (SCGB3A2). RESULTS: During 2.2â¯years of follow-up, OPN, OPG, and HBP levels predicted the composite endpoint (univariable hazard ratio [95% confidence interval] per 1SD increase: 2.31 [1.76-3.15], 2.23 [1.69-3.00], and 1.36[1.09-1.70]). Independently of the biomarkers' levels, the slopes of OPG, TFF-3, PSP-D trajectories were also strong clinical predictors (per 0.1SD increase: 1.24 [1.14-1.38], 1.31 [1.17-1.49], and 1.32 [1.21-1.47]). All associations persisted after multivariable adjustment for baseline characteristics, and repeatedly assessed CHF pharmacological treatment and cardiac biomarkers NT-proBNP and troponin T. CONCLUSIONS: Repeatedly-measured levels of OPN, OPG, and HBP, and slopes of OPG, TFF-3, and PSP-D strongly predict clinical outcome. These candidate biomarkers may be clinically relevant as they could further define a patient's risk and provide additional pathophysiological insights into CHF.
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Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/epidemiologia , Rim/metabolismo , Pulmão/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doença Crônica , Estudos de Coortes , Receptores ErbB/sangue , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Transplante de Coração/tendências , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Países Baixos/epidemiologia , Osteoprotegerina/sangue , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Fatores de TempoRESUMO
Background Remodeling biomarkers carry high potential for predicting adverse events in chronic heart failure ( CHF ) patients. However, temporal patterns during the course of CHF , and especially the trajectory before an adverse event, are unknown. We studied the prognostic value of temporal patterns of 14 cardiac remodeling biomarker candidates in stable patients with CHF from the Bio-SHiFT (Serial Biomarker Measurements and New Echocardiographic Techniques in Chronic Heart Failure Patients Result in Tailored Prediction of Prognosis) study. Methods and Results In 263 CHF patients, we performed trimonthly blood sampling during a median follow-up of 2.2 years. For the analysis, we selected all baseline samples, the 2 samples closest to the primary end point ( PE ), or the last sample available for end point-free patients. Thus, in 567 samples, we measured suppression of tumorigenicity-2, galectin-3, galectin-4, growth differentiation factor-15, matrix metalloproteinase-2, 3, and 9, tissue inhibitor metalloproteinase-4, perlecan, aminopeptidase-N, caspase-3, cathepsin-D, cathepsin-Z, and cystatin-B. The PE was a composite of cardiovascular mortality, heart transplantation, left ventricular assist device implantation, and HF hospitalization. Associations between repeatedly measured biomarker candidates and the PE were investigated by joint modeling. Median age was 68 (interquartile range: 59-76) years with 72% men; 70 patients reached the PE . Repeatedly measured suppression of tumorigenicity-2, galectin-3, galectin-4, growth differentiation factor-15, matrix metalloproteinase-2 and 9, tissue inhibitor metalloproteinase-4, perlecan, cathepsin-D, and cystatin-B levels were significantly associated with the PE , and increased as the PE approached. The slopes of biomarker trajectories were also predictors of clinical outcome, independent of their absolute level. Associations persisted after adjustment for clinical characteristics and pharmacological treatment. Suppression of tumorigenicity-2 was the strongest predictor (hazard ratio: 7.55 per SD difference, 95% CI : 5.53-10.30), followed by growth differentiation factor-15 (4.06, 2.98-5.54) and matrix metalloproteinase-2 (3.59, 2.55-5.05). Conclusions Temporal patterns of remodeling biomarker candidates predict adverse clinical outcomes in CHF . Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01851538.
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Biomarcadores/sangue , Insuficiência Cardíaca/sangue , Remodelação Ventricular , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
BACKGROUND: We aimed to compare the prognostic value of a single "baseline" echocardiogram with repeated echocardiography in stable chronic heart failure (CHF) patients. We hypothesized that repeated echocardiograms would contain incremental prognostic information. METHODS: In the prospective Bio-SHiFT study, we performed 332 echocardiograms in 106 patients during a median follow-up of 2.3 years. The endpoint comprised HF hospitalization, left ventricular (LV) assist device implantation, heart transplantation, and cardiovascular death. We compared hazard ratios (HRs; adjusted for N-terminal pro-brain natriuretic peptide) from Cox models for the first available measurement with HRs from joint models, which model individual trajectories based on the repeated measurements and link these to the time-to-event data. RESULTS: The mean age of the patients was 58.1 years; 78.3% were male, 12.6% had New York Heart Association class >II, all had reduced ejection fraction, and the most common HF etiologies were cardiomyopathies (51%) and ischemia (40%). The endpoint occurred in 25 patients. Both the single measurements and the temporal trajectories were significantly associated with the endpoint (adjusted HR Cox model [95% CI] vs adjusted HR joint model [95% CI]): LV ejection fraction, 1.47 (0.93-2.31) vs 1.77 (1.13-2.93); diastolic LV diameter, 1.64 (1.09-2.47) vs 1.68 (1.12-2.57); systolic LV diameter, 1.72 (1.10-2.69) vs 1.68 (1.13-2.63); systolic left atrial diameter, 1.88 (1.18-3.00) vs 2.60 (1.48-4.97); E/A ratio, 2.73 (1.42-5.26) vs 3.87 (1.75-10.13); and E/e' ratio, 2.30 (1.38-3.84) vs 2.99 (1.68-6.19). None of the trajectories from the investigated parameters showed worsening prior to events. CONCLUSIONS: Although single baseline or repeatedly measured echocardiographic parameters were associated with the endpoint, all parameters remained on average stable during the 2.3 years of follow-up in this largely minimally symptomatic CHF cohort. Thus, regular echocardiographic monitoring of systolic or diastolic LV function within this time frame does not carry incremental prognostic information over a single baseline measurement.
Assuntos
Ecocardiografia , Insuficiência Cardíaca/diagnóstico por imagem , Biomarcadores/análise , Doença Crônica , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Prognóstico , Estudos Prospectivos , RetratamentoRESUMO
Purpose: Multiple hormonal and metabolic alterations occur in chronic heart failure (CHF), but their proper monitoring during clinically silent progression of CHF remains challenging. Hence, our objective was to explore whether temporal patterns of six emerging cardiometabolic biomarkers predict future adverse clinical events in stable patients with CHF. Methods: In 263 patients with CHF, we determined the risk of a composite end point of heart failure hospitalization, cardiac death, left ventricular assist device implantation, and heart transplantation in relation to serially assessed blood biomarker levels and slopes (i.e., rate of biomarker change per year). During 2.2 years of follow-up, we repeatedly measured IGF binding proteins 1, 2, and 7 (IGFBP-1, IGFBP-2, IGFBP-7), adipose fatty acid binding protein 4 (FABP-4), resistin, and chemerin (567 samples in total). Results: Serially measured IGFBP-1, IGFBP-2, IGFBP-7, and FABP-4 levels predicted the end point [univariable hazard ratio (95% CI) per 1-SD increase: 3.34 (2.43 to 4.87), 2.86 (2.10 to 3.92), 2.45 (1.91 to 3.13), and 2.46 (1.88 to 3.24), respectively]. Independently of the biomarkers' levels, their slopes were also strong clinical predictors [per 0.1-SD increase: 1.20 (1.11 to 1.31), 1.27 (1.14 to 1.45), 1.23 (1.11 to 1.37), and 1.27 (1.12 to 1.48)]. All associations persisted after multivariable adjustment for patient baseline characteristics, baseline N-terminal pro-hormone brain natriuretic peptide and cardiac troponin T, and pharmacological treatment during follow-up. Main Conclusions: The temporal patterns of IGFBP-1, IGFBP-2, IGFBP-7, and adipose FABP-4 predict adverse clinical outcomes during outpatient follow-up of patients with CHF and may be clinically relevant as they could help detect more aggressive CHF forms and assess patient prognosis, as well as ultimately aid in designing more effective biomarker-guided therapy.