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PURPOSE OF REVIEW: Neurohormonal blockade and device-based therapies for heart failure (HF) greatly reduce morbidity and mortality. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated benefits in patients with HF across a broad range of phenotypes. In addition to SGLT2i, drugs targeting novel pathways have demonstrated benefit in heart failure with reduced ejection fraction (HFrEF). This review will provide an update on recent advances in the medical management of HF, highlighting the role of SGLT2i, vericiguat and omecamtiv mecarbil, along with new evidence on the benefit of rapid up-titration of guideline-directed medical therapy (GDMT) in patients with acute HF. RECENT FINDINGS: Dapagliflozin and empagliflozin reduce the risk of HF hospitalization and cardiovascular (CV) death in HF patients regardless of left ventricular ejection fraction (LVEF) and diabetes status. Their true mechanism of action in HF is not yet defined. Vericiguat, a stimulator of guanylate cyclase, and omecamtiv mecarbil, a cardiac myotrope, have shown benefit in HFrEF. Rapid up-titration of GDMT in patients hospitalized with HF is safe and results in improved clinical outcomes. SUMMARY: SGLT2i have earned their place as the fourth pillar of HF medical therapy alongside sacubitril-valsartan, evidence-based beta-blockers and mineralocorticoid receptor antagonists. They should be considered for the treatment of all symptomatic patients across the entire range of HF phenotypes, including patients hospitalized with HF. Vericiguat benefits high risk patients with worsening HF clinical profile. Most patients hospitalized with HF can be up-titrated to high doses of GDMT within weeks and this approach reduces the likelihood of adverse HF outcomes.
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Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/terapia , Volume Sistólico , Função Ventricular Esquerda , Resultado do TratamentoRESUMO
This work aims to estimate the voltinism differences in the studied lines and the influence of biological and environmental variables on this trait. Three Bombyx mori. lines were used. One polyvoltine (Indian, C. Nichi) and two bivoltine (Chinese6-C6 and Japanese7-J7). Silkworms were reared under controlled conditions of temperature (24±1, 26±1, 28±1°C) and photoperiod (8-16, 12-12, 16-8 light/darkness) during the life cycle. The measured biological characters were duration of larval period (DLP), larval weight on fifth day of V instar (LW(V-5)), rate of weight (RWV), duration of life cycle (DLC), fecunditiy (NE), fertility (F) and voltinism (V). Voltinism was estimated using a linear regression model; the variables that influence voltinism were found using a multiple regression analysis; and the effect of environmental conditions on change of voltinism employing an ANOVA. The results show that the variables that affect voltinism are different for each line, which demonstrates the effect of the line factor. Nichi voltinism was affected by the six measured variables, while in C6 and J7 where voltinisms depends on the duration of diapause, some variables were excluded from the model. In Indian tropical polyvoltine, the temperature was the influencing factor, while in Chinese and Japanese bivoltines lines was the photoperiod.
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Bombyx , Animais , Estágios do Ciclo de Vida , Larva , Temperatura , FertilidadeRESUMO
High volume extracorporeal membrane oxygenation (ECMO) centers have developed mobile ECMO programs in recent years to facilitate the implementation of ECMO support at hospitals with lower capabilities, and transfer these patients for further care. We report a case of mobile ECMO on a patient with coronavirus disease 2019-related acute respiratory distress syndrome, and discuss the potential application in the current severe acute respiratory syndrome coronavirus 2 pandemic.
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COVID-19/complicações , Oxigenação por Membrana Extracorpórea/métodos , Pandemias , Insuficiência Respiratória/terapia , SARS-CoV-2 , COVID-19/epidemiologia , Humanos , Pessoa de Meia-Idade , Insuficiência Respiratória/etiologiaRESUMO
BACKGROUND: The aim of this study is to evaluate and define the expected flow pattern changes of carotid artery duplex ultrasound after left ventricular assist device (LVAD) placement. METHODS: Retrospective review of Henry Ford Hospital database of patients who had undergone LVAD placement between March 2008 and July 2012 was performed. All patients who had carotid artery duplex scanning before and after LVAD placement within 2 years of each other and showed <50% stenosis were included in this study. Type of waveform, carotid peak systolic velocity, and end-diastolic velocities were analyzed, and the values were compared before and after LVAD placement. RESULTS: A total of 13 patients with LVAD had at least 2 carotid duplex studies before and after LVAD placement within 2 years of each other. Of those, 92% (n = 12) were men, and 61% (n = 8) were Caucasian. Mean age was 61 years old. The HeartWare ventricular assist device was implanted in 4 patients and the HeartMate II left ventricular assist device was implanted in 9 patients. Post-LVAD Doppler imaging demonstrated parvus tardus waveform. Analysis of flow velocities revealed that peak systolic velocity was diminished after LVAD placement in both the internal and common carotid arteries (P = 0.006 and P < 0.0001, respectively). End-diastolic velocity, however, increased post-LVAD (P < 0.0001). Interestingly, mean flow velocities in both the common and internal carotid arteries remained stable after LVAD placement. CONCLUSIONS: This study reveals changes in waveform morphology and peak systolic and diastolic velocities in the common and internal carotid arteries on carotid duplex after LVAD placement. Additionally, it shows that despite changes in post-LVAD pulse pressure in the carotid arteries, the mean flow velocity remained unchanged.
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Artéria Carótida Primitiva/fisiopatologia , Estenose das Carótidas/fisiopatologia , Insuficiência Cardíaca/terapia , Coração Auxiliar , Função Ventricular Esquerda , Idoso , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/fisiopatologia , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Bases de Dados Factuais , Progressão da Doença , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Michigan , Pessoa de Meia-Idade , Desenho de Prótese , Fluxo Sanguíneo Regional , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler em CoresRESUMO
BACKGROUND: Although cardiopulmonary exercise (CPX) testing in patients with heart failure and reduced ejection fraction is well established, there are limited data on the value of CPX variables in patients with HF and preserved ejection fraction (HFpEF). We sought to determine the prognostic value of select CPX measures in patients with HFpEF. METHODS: This was a retrospective analysis of patients with HFpEF (ejection fraction ≥ 50%) who performed a CPX test between 1997 and 2010. Selected CPX variables included peak oxygen uptake (VO2), percent predicted maximum oxygen uptake (ppMVO2), minute ventilation to carbon dioxide production slope (VE/VCO2 slope) and exercise oscillatory ventilation (EOV). Separate Cox regression analyses were performed to assess the relationship between each CPX variable and a composite outcome of all-cause mortality or cardiac transplant. RESULTS: We identified 173 HFpEF patients (45% women, 58% non-white, age 54 ± 14 years) with complete CPX data. During a median follow-up of 5.2 years, there were 42 deaths and 5 cardiac transplants. The 1-, 3-, and 5-year cumulative event-free survival was 96%, 90%, and 82%, respectively. Based on the Wald statistic from the Cox regression analyses adjusted for age, sex, and ß-blockade therapy, ppMVO2 was the strongest predictor of the end point (Wald χ(2) = 15.0, hazard ratio per 10%, P < .001), followed by peak VO2 (Wald χ(2) = 11.8, P = .001). VE/VCO2 slope (Wald χ(2)= 0.4, P = .54) and EOV (Wald χ(2) = 0.15, P = .70) had no significant association to the composite outcome. CONCLUSION: These data support the prognostic utility of peak VO2 and ppMVO2 in patients with HFpEF. Additional studies are needed to define optimal cut points to identify low- and high-risk patients.
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Teste de Esforço/tendências , Insuficiência Cardíaca/diagnóstico , Volume Sistólico/fisiologia , Cateterismo Cardíaco , Progressão da Doença , Intervalo Livre de Doença , Ecocardiografia , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida/tendências , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors (GLP-1 agents) may be protective in heart failure (HF). We set out to determine whether GLP-1 agent use is associated with HF risk in diabetics. METHODS AND RESULTS: In this retrospective cohort study of members of a large health system, we identified >19,000 adult diabetics from January 1, 2000, to July 1, 2012. GLP-1 agent users were matched 1:2 to control subjects with the use of propensity matching based on age, race, sex, coronary disease, HF, diabetes duration, and number of antidiabetic medications. The association of GLP-1 agents with time to HF hospitalization was tested with multivariable Cox regression. All-cause hospitalization and mortality were secondary end points. We identified 1,426 users of GLP-1 agents and 2,798 control subjects. Both were similar except for angiotensin-converting enzyme inhibitors/angiotensin receptor blocker use, number of antidiabetic medications, and age. There were 199 hospitalizations, of which 128 were for HF, and 114 deaths. GLP-1 agents were associated with reduced risk of HF hospitalization (adjusted hazard ratio [aHR] 0.51, 95% confidence interval [CI] 0.34-0.77; P = .002), all-cause hospitalization (aHR 0.54, 95% CI 0.38-0.74; P = .001), and death (aHR 0.31, 95% CI 0.18-0.53; P = .001). CONCLUSIONS: GLP-1 agents may reduce the risk of HF events in diabetics.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Peptídeo 1 Semelhante ao Glucagon/agonistas , Insuficiência Cardíaca/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Idoso , Estudos de Coortes , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Feminino , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/metabolismo , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Many studies have shown a strong association between numerous variables from a cardiopulmonary exercise (CPX) test and prognosis in patients with heart failure with reduced ejection fraction (HFrEF). However, few studies have compared the prognostic value of a majority of these variables simultaneously, so controversy remains regarding optimal interpretation. METHODS AND RESULTS: This was a retrospective analysis of patients with HFrEF (n = 1,201; age = 55 ± 13 y; 33% female) and a CPX test from 1997 to 2010. Thirty variables from a CPX test were considered in separate adjusted Cox regression analyses to describe the strength of the relation of each to a composite end point of all-cause mortality, left ventricular assist device implantation, or heart transplantation. During a median follow-up of 3.8 years, there were 577 (48.0%) events. The majority of variables were highly significant (P < .001). Among these, percentage of predicted maximum VËO2 (ppMVËO2; Wald = 203; P < .001; C-index = 0.73) was similar to VE-VCO2 slope (Wald = 201; P < .001; C = 0.72) and peak VËO2 (Wald = 161; P < .001; C = 0.72). In addition, there was no significant interaction observed for peak respiratory exchange ratio <1 vs ≥1. CONCLUSIONS: Consistent with prior studies, many CPX test variables were strongly associated with prognosis in patients with HFrEF. The choice of which variable to use is up to the clinician. Renewed attention should be given to ppMVËO2, which appears to be highly predictive of survival in these patients.
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Exercício Físico/psicologia , Insuficiência Cardíaca Sistólica/diagnóstico , Causas de Morte/tendências , Teste de Esforço/métodos , Feminino , Seguimentos , Insuficiência Cardíaca Sistólica/mortalidade , Insuficiência Cardíaca Sistólica/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Índice de Gravidade de Doença , Volume Sistólico , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologiaRESUMO
The incidence of heart failure (HF) and diabetes mellitus is rapidly increasing and is associated with poor prognosis. In spite of the advances in therapy, HF remains a major health problem with high morbidity and mortality. When HF and diabetes coexist, clinical outcomes are significantly worse. The relationship between these two conditions has been studied in various experimental models. However, the mechanisms for this interrelationship are complex, incompletely understood, and have become a matter of considerable clinical and research interest. There are only few animal models that manifest both HF and diabetes. However, the translation of results from these models to human disease is limited, and new models are needed to expand our current understanding of this clinical interaction. In this review, we discuss mechanisms of insulin signaling and insulin resistance, the clinical association between insulin resistance and HF, and its proposed pathophysiologic mechanisms. Finally, we discuss available animal models of insulin resistance and HF and propose requirements for future new models.
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Diabetes Mellitus Experimental/sangue , Insuficiência Cardíaca/sangue , Resistência à Insulina , Insulina/sangue , Animais , Diabetes Mellitus Experimental/complicações , Modelos Animais de Doenças , Insuficiência Cardíaca/complicações , HumanosRESUMO
AIMS: Transthyretin cardiac amyloidosis (ATTR-CA) is most often associated with heart failure with preserved ejection fraction (HFpEF). However, patients may present with impaired systolic function at the time of diagnosis, which has not been widely investigated. We sought to explore the prevalence of various heart failure (HF) phenotypes and their associated clinical characteristics at the time of ATTR-CA diagnosis. METHODS: We performed a single-centre retrospective cohort study of consecutive patients with ATTR-CA evaluated between February 2016 and December 2022. Data on patient demographics, comorbidities, imaging and laboratory findings were compared across HF phenotypes (age: 78.1 ± 8.6 years, with 91.1% male). A total of 21.6% (n = 46) presented with heart failure with reduced ejection fraction (HFrEF), 17.8% (n = 38) with heart failure with mildly reduced ejection fraction (HFmrEF) and 60.6% (n = 129) with HFpEF at the time of diagnosis with ATTR-CA. Those presenting with HFrEF or HFmrEF were more likely to be African American and had significantly worse New York Heart Association (NYHA) functional class, higher N-terminal pro-brain natriuretic peptide (NT-proBNP) and higher serum creatinine levels as compared with those with HFpEF. CONCLUSIONS: Although ATTR-CA is traditionally thought to be seen primarily among patients with HFpEF, our data suggest that ATTR-CA has a higher prevalence among patients with HFrEF, which underscores the importance of heightened clinical suspicion regardless of ejection fraction when considering ATTR-CA. Furthermore, although comorbidities are similar, patients with HFmrEF and HFrEF had a worse symptom burden.
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BACKGROUND: In patients with transthyretin cardiac amyloidosis (ATTR-CA), renal dysfunction is a poor prognostic indicator. Limited data are available on variables that portend worsening renal function (wRF) among ATTR-CA patients. OBJECTIVES: This study assesses which characteristics place patients at higher risk for the development of wRF (defined as a drop of ≥10% in glomerular filtration rate [GFR]) within the first year following diagnosis of ATTR-CA. METHODS: We included patients with ATTR-CA (n = 134) evaluated between 2/2016 and 12/2022 and followed for up to 1 year at our amyloid clinic. Patients were stratified into two groups: a group with maintained renal function (mRF) and a group with wRF and compared using appropriate testing. Significant variables in the univariate analysis were included in the multivariable logistic regression model to determine characteristics associated with wRF. RESULTS: Within a follow-up period of 326 ± 118 days, the median GFR% change measured -6% [-18%, +8]. About 41.8% (n = 56) had wRF, while the remainder had mRF. In addition, in patients with no prior history of chronic kidney disease (CKD), 25.5% developed de novo CKD. On multivariable logistic regression, only New York Heart Association (NYHA) class ≥III (odds ratio [OR]: 3.9, 95% confidence interval [CI]: [1.6-9.3]), history of ischemic heart disease (IHD) (OR: 0.3, 95% CI: [0.1-0.7]), and not receiving SGLT-2i (OR: 0.1, 95% CI: [0.02-0.5]) were significant predictors of wRF. CONCLUSION: Our study demonstrated that the development of de novo renal dysfunction or wRF is common following the diagnosis of ATTR-CA. Additionally, we identified worse NYHA class and no prior history of IHD as significant predictors associated with developing wRF, while receiving SGLT-2i therapy appeared to be protective in this population.
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Neuropatias Amiloides Familiares , Cardiomiopatias , Taxa de Filtração Glomerular , Humanos , Masculino , Feminino , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/diagnóstico , Neuropatias Amiloides Familiares/fisiopatologia , Idoso , Cardiomiopatias/diagnóstico , Cardiomiopatias/fisiopatologia , Cardiomiopatias/etiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Pessoa de Meia-Idade , Seguimentos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Progressão da Doença , Rim/fisiopatologia , Fatores de Tempo , Incidência , Medição de Risco/métodosRESUMO
There is vast evidence that accounts for the association between entrepreneurial orientation (EO) and the probability of starting a business (PSB). However, there are not many studies that test how psychological factors moderate this relationship. A variable that has been little studied in this relationship is Grit. Grit is considered a personality trait defined as perseverance and passion for long-term goals. Grit considers two sub-dimensions, one linked to the consistency of interests (Grit-Passion) and the other linked to perseverance in the effort (Grit-Perseverance). The objective of this article is to analyze the moderating role that both sub-dimensions of grit plays in the relationship between EO and PSB, considering its interaction with sociodemographic variables such as age, gender, and culture. This cross-sectional study has a sample of 1,761 participants, active workers (49.8% men; mean age 41.15 years, SD = 12.72 years; 22.9% Colombian and 77.1% Spanish). The EO scale and a Grit Scale were applied. In addition, participants were asked, based on their perception, how likely they were to start their own business within the next 5 years. A simple moderation analysis was considered to test the moderating role of grit in the relationship between EO and PSB. Subsequently, a double moderation analysis was carried out in order to identify which sociodemographic variables moderate the moderating effect of grit on the relationship in question. The results show that only the Grit-Passion component of grit moderates the relationship between EO and PSB. Regarding the sociodemographic variables, neither age, culture, nor gender showed a moderating effect on the moderation exercised by Grit-Passion in the relationship between OE and PSB. The results are discussed in terms of psychological capital, particularly with an emphasis on explaining why only the Grit-Passion shows a moderating effect on the relationship between EO and PSB, in detriment of Grit-Perseverance. In addition, the power of grit in the field of entrepreneurship is discussed, considering that its moderating effect is transversal to variations in age, gender and culture, as well as its relevance when considering interventions and pedagogical models in the field of entrepreneurship.
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Although the correlation between Entrepreneurial Orientation (EO) and concrete actions to set up a business or the Probability of Starting a Business (PSB) has been widely studied, the psychological factors that can affect this relationship have not yet been sufficiently addressed in the field of entrepreneurship. One of them is curiosity. Both at theoretical and empirical level, a distinction are usually made between two types of curiosity. I-type curiosity is associated with the anticipated pleasure of discovering something new, and D-type curiosity is associated with reducing uncertainty and eliminating unwanted states of ignorance. Consequently, this paper aims to analyze the moderating role that the types of curiosity play in the relationship between EO and PSB, considering their interaction with sociodemographic variables. The sample of this cross-sectional study consisted of 1,761 participants (convenience sampling of active workers; 49.8% men; mean age 38.88 years, SD = 12.53 years; 22.9% Colombian and 77.1% Spanish). The EO scale and a curiosity scale were applied. In addition, participants were asked, based on their perception, how likely they were to start their own business within the next 5 years. A simple moderation analysis was considered to test the moderating role of both types of curiosity in the relationship between EO and PSB. Next, a double moderation analysis was carried out in order to identify, which sociodemographic variables moderate the moderating effect of curiosity. The results show that only the D-type component moderates the relationship between EO and PSB: The higher the D-type curiosity, the stronger the association between EO and PSB. In terms of sociodemographic variables, neither culture nor gender showed a moderating effect on the moderation exerted by D-type curiosity. While, age did moderate the moderating effect of D-type curiosity on the relationship between EO and PSB. Results are discussed in terms of spirituality (attitudes, practices, and behaviors) and the resolution of problems associated with the entrepreneurial process, considering cognitive and psychological factors, particularly with an emphasis on explaining why only D-type curiosity shows a moderating effect. Finally, the limitations of the study and potential future lines of research are pointed out.
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Arrhythmogenic right ventricular cardiomyopathy and cardiac sarcoidosis can both present with ventricular tachycardia. We report a case of a patient whose histological diagnosis was not only confirmed by the transplanted heart but who also underwent successful transplantation after overcoming COVID-19.
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The effects of treadmill workstation use on kinematic gait symmetry and computer work performance remain unclear. The purpose of this pilot study was to analyze the effects of treadmill workstation use on lower body motion symmetry while performing a typing task when compared to overground and treadmill walking. The lower body motion of ten healthy adults (6 males and 4 females) was recorded by a motion capture system. Hip, knee, and ankle joint rotations were computed and compared for each condition. Despite comparable lower body kinematic gait asymmetries across conditions, asymmetric knee flexion motions at early gait cycle were only found in treadmill workstation users (left knee significantly more flexed than the right one). This demonstrates that the interaction between walking and another task is dependent on the task cognitive content. Our findings suggest that lower body kinematic gait symmetry may be influenced by the use of treadmill workstations.
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Marcha , Articulação do Joelho/fisiologia , Extremidade Inferior/fisiologia , Amplitude de Movimento Articular , Caminhada , Adolescente , Adulto , Fenômenos Biomecânicos , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto JovemRESUMO
OBJECTIVE: Ventricular assist devices (VADs) have been implanted since 1990 in our institution, becoming an increasingly common treatment for end-stage heart failure. Beginning in 1997, VAD patients were discharged home when feasible. In August 2003, a dedicated multidisciplinary VAD team (cardiac surgeons, cardiologists, VAD coordinators, nurses, rehabilitation specialists, nutrition experts, psychologists, pharmacists, social workers, and administrators) was created to optimize the management of VAD patients. The purpose of this study is to analyze the impact of these changes in care at our center over the last 17 years. METHODS: We retrospectively studied 107 consecutive VAD recipients between June 1990 and August 2006. VADs were implanted as bridge to recovery, bridge to transplant and destination therapy. The cohort was divided by care plans into early (n=37, June 1990-1996), mid (n=32, 1997-July 2003), and late groups (n=38, August 2003-August 2006). Demographic profile, survival and complications were assessed. RESULTS: Patient demographics tended to show an increased severity of illness over time. Post-VAD survival rate significantly improved in the late group (post-VAD 1- and 3-year survival rates; early: 54.1% and 40.5%; mid: 51.6% and 41.9%; late: 86.8% and 82.5%, p<0.001, respectively). The incidence of complications including re-operation, major bleeding and major infection, significantly decreased in the late group (p<0.05). CONCLUSIONS: Outcomes have improved dramatically in recent VAD patients, despite an increasingly high-risk patient population. These data suggest that advances in device technology and medical therapies, as well as a multidisciplinary approach, have improved survival on VAD therapy.
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Insuficiência Cardíaca/terapia , Coração Auxiliar , Adulto , Idoso , Antibioticoprofilaxia , Métodos Epidemiológicos , Feminino , Insuficiência Cardíaca/mortalidade , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente/organização & administração , Seleção de Pacientes , Complicações Pós-Operatórias , Prognóstico , Reoperação , Resultado do TratamentoRESUMO
Direct and specific inhibition of factor Xa is an emerging therapeutic strategy for atherothrombotic disease. Parenteral factor Xa inhibitors promise efficacy comparable to standard therapies, which could be extended to ambulatory patients with oral agents. We evaluated the antithrombotic effect of the oral, direct factor Xa inhibitor DU-176b in a phase-I study. Healthy subjects (n = 12) received a single, 60 mg dose of DU-176b. Antithrombotic effects were assessed by comparing ex-vivo thrombus formation at 1.5, 5, and 12 hours post-dose versus baseline, along with factor Xa activity, thrombin generation and clotting parameters. Under venous flow after 1.5 and 5 hours, the thrombus was 28% and 21% smaller versus baseline, respectively (p < 0.05). Under arterial condition, the reduction was 26% and 17% (p < 0.05). Thrombin generation decreased by 28% at 1.5 hours and 10% at 5 hours. Changes in PT and INR correlated well with plasma drug concentrations (R2 = 0.79 and 0.78). Direct and specific inhibition of factor Xa by DU-176b significantly reduced ex-vivo thrombus formation at both venous and arterial rheologies, up to 5 hours post-dose. The effects mirrored changes in clotting parameters, suggesting their potential usefulness for monitoring in a clinical setting.
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Anticoagulantes/uso terapêutico , Antitrombina III/farmacologia , Inibidores do Fator Xa , Fator Xa/química , Fibrinolíticos/farmacologia , Trombose/imunologia , Trombose/terapia , Adulto , Antitrombina III/química , Coagulação Sanguínea , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Tempo de Protrombina , Estresse Mecânico , Trombina/metabolismo , Trombose/tratamento farmacológico , Fatores de TempoRESUMO
UNLABELLED: The American College of Sports Medicine currently recommends the HR reserve (HRR) method to guide exercise in individuals who have heart failure with reduced ejection fraction. This recommendation is based on the known association between %HRR and percentage of VËO2 reserve (%VËO2R) in this population. However, to our knowledge, no studies exist regarding this relation in individuals with a left ventricular assist device (LVAD). PURPOSE: This article aimed to describe the relation between VËO2 and surrogate markers of exercise intensity among patients with LVAD. METHODS: Patients with continuous-flow LVAD (n = 24, seven females) completed a symptom-limited graded exercise test on a treadmill. HR and VËO2 were measured continuously and averaged every 20 s. Regression equations were determined using a generalized estimating equation to predict %VËO2R from %HRR, Borg RPE, and LVAD flow, overall and stratified by presence of pacing. RESULTS: Although the association between %HRR and %VËO2R was good (R = 0.75), the slope and y-intercept for %HRR versus %VËO2R was different from the line of identity (P = 0.002). However, when paced subjects were excluded (n = 8) from the analysis, there was no significant difference between the slope and y-intercept (= 0.036 + 0.937 × %HRR; SEE, 2%; P = 0.052). RPE showed a strong association with %VËO2R (R = 0.84), whereas LVAD flow showed a weak (albeit statistically significant) association (R = 0.05). Both had slopes and y-intercepts that were different from the line of identity (P < 0.05). CONCLUSIONS: In patients with LVAD who are not paced during exercise, the use of %HRR is a good predictor of %VËO2R. However, for patients in this population who are also paced during exercise, RPE is a suitable surrogate measure of exercise intensity.
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Exercício Físico/fisiologia , Frequência Cardíaca , Coração Auxiliar , Consumo de Oxigênio , Adulto , Idoso , Teste de Esforço , Tolerância ao Exercício , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Disappointing survival rates from out-of-hospital cardiac arrests encourage strategies for faster defibrillation, such as use of automated external defibrillators (AEDs) by nonconventional responders. METHODS AND RESULTS: AEDs were provided to all Miami-Dade County, Florida, police. AED-equipped police (P-AED) and conventional emergency medical rescue (EMS) responders are simultaneously deployed to possible cardiac arrests. Times from 9-1-1 contact to the scene were compared for P-AED and concurrently deployed EMS, and both were compared with historical EMS experience. Survival with P-AED was compared with outcomes when EMS was the sole responder. Among 420 paired dispatches of P-AED and EMS, the mean+/-SD P-AED time from 9-1-1 call to arrival at the scene was 6.16+/-4.27 minutes, compared with 7.56+/-3.60 minutes for EMS (P<0.001). Police arrived first to 56% of the calls. The time to first responder arrival among P-AED and EMS was 4.88+/-2.88 minutes (P<0.001), compared with a historical response time of 7.64+/-3.66 minutes when EMS was the sole responder. A 17.2% survival rate was observed for victims with ventricular fibrillation or pulseless ventricular tachycardia (VT/VF), compared with 9.0% for standard EMS before P-AED implementation (P=0.047). However, VT/VF benefit was diluted by the observation that 61% of the initial rhythms were nonshockable, reducing the absolute survival benefit among the total study population to 1.6% (P-AED, 7.6%; EMS, 6.0%). CONCLUSIONS: P-AED establishes a layer of responders that generate improved response times and survival from VT/VF. There was no benefit for victims with nonshockable rhythms.
Assuntos
Reanimação Cardiopulmonar/instrumentação , Morte Súbita Cardíaca/prevenção & controle , Cardioversão Elétrica/tendências , Parada Cardíaca/terapia , Polícia/tendências , Características de Residência , Idoso , Reanimação Cardiopulmonar/métodos , Reanimação Cardiopulmonar/tendências , Comunicação , Cardioversão Elétrica/estatística & dados numéricos , Serviços Médicos de Emergência/organização & administração , Serviços Médicos de Emergência/tendências , Segurança de Equipamentos , Feminino , Florida , Parada Cardíaca/mortalidade , Humanos , Masculino , Polícia/organização & administração , Ressuscitação/estatística & dados numéricos , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do TratamentoRESUMO
Out-of-hospital cardiac arrest remains a major epidemiologic, clinical, scientific, and public health challenge. Emergency rescue systems (EMS) based in fire departments initially demonstrated encouraging outcomes as new strategies were developed in communities led by people committed to such programs, but the overall impact on survival has been modest. With improvement in automated external defibrillator (AED) technology in recent years, there has been increasing interest in their use by non-conventional responders in recent years. In parallel with the AED strategies, adjunctive strategies and therapies have been developed. These include the demonstration that interventions targeted to reperfusion of the ischemic myocardium, such as thrombolytic therapy given by EMS responders, clarification of the role of intravenous amiodarone for electrophysiologically-resistant cardiac arrest victims, and demonstration of a role for hypothermia in post-cardiac arrest. Thus, the range of pre-hospital and in-hospital strategies for improving cardiac arrest survival continues to broaden. The major lesson learned during the past two decades is that no single strategy can be relied upon to yield a major impact on the mortality from out-of-hospital cardiac arrest. The cumulative effect of multiple strategies, working together toward the same goal, will ultimately provide additive effects on outcomes. Carefully thought out strategic approaches can maximize the effect on total mortality.