Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 283
Filtrar
1.
J Am Coll Cardiol ; 74(7): 889-901, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31416533

RESUMO

BACKGROUND: Phosphodiesterase-9 (PDE9) reduces natriuretic peptide (NP) signaling and may be involved in the pathophysiology of heart failure (HF). OBJECTIVES: This study investigated for the first time the integrated hemodynamic, endocrine, and renal effects of phosphodiesterase-9 inhibition (PDE9-I). METHODS: A total of 8 normal sheep and 8 sheep with pacing-induced HF received incremental intravenous boluses of PDE9-I (30, 100, and 300 mg PF-04749982 at 1-h intervals). RESULTS: PDE9-I dose-dependently increased plasma cyclic guanosine monophosphate (cGMP) in normal sheep (p < 0.05) while concurrently reducing circulating atrial natriuretic peptide levels (p < 0.01). Similar trends were evident in HF, resulting in significant elevations in the cGMP/NP ratio in both states (p < 0.001 and p < 0.05, respectively). PDE9-I also produced progressive falls in arterial pressure (HF: p < 0.001), atrial pressure (Normal: p < 0.001; HF: p < 0.001), and peripheral resistance (HF: p < 0.001), and transiently increased cardiac output at the top dose (Normal: p < 0.05; HF: p < 0.001). Inhibition of PDE9 had a negligible effect on circulating hormones at the lower doses, but post-high dose, acutely increased renin activity (Normal: p < 0.001; HF: p < 0.05), vasopressin (Normal: p < 0.001; HF: p < 0.01), and cyclic adenosine monophosphate (HF: p < 0.001). Plasma aldosterone increased briefly after high-dose PDE9-I in normal sheep, and fell following the top dose in HF. PDE9-I dose-dependently increased urinary cGMP in both states (both p < 0.001). In HF, this was associated with increases in urine volume (p < 0.01), sodium excretion (p < 0.01), and creatinine clearance (p < 0.001). CONCLUSIONS: PDE9-I improves NP efficacy in conjunction with beneficial hemodynamic and renal effects in experimental HF. These results support a role for PDE9 in HF pathophysiology and suggest its inhibition may constitute a novel therapeutic approach to this disease.

2.
J Am Heart Assoc ; 8(17): e013114, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31431116

RESUMO

Background Diabetes mellitus frequently coexists with heart failure (HF), but few studies have compared the associations between diabetes mellitus and cardiac remodeling, quality of life, and clinical outcomes, according to HF phenotype. Methods and Results We compared echocardiographic parameters, quality of life (assessed by the Kansas City Cardiomyopathy Questionnaire), and outcomes (1-year all-cause mortality, cardiovascular mortality, and HF hospitalization) between HF patients with and without type 2 diabetes mellitus in the prospective ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) Registry, as well as community-based controls without HF. Adjusted Cox proportional hazards models were used to assess the association of diabetes mellitus with clinical outcomes. Among 5028 patients with HF and reduced ejection fraction (HFrEF; EF <40%) and 1139 patients with HF and preserved EF (HFpEF; EF ≥50%), the prevalences of type 2 diabetes mellitus were 40.2% and 45.0%, respectively (P=0.003). In both HFrEF and HFpEF cohorts, diabetes mellitus (versus no diabetes mellitus) was associated with smaller indexed left ventricular diastolic volumes and higher mitral E/e' ratio. There was a predominance of eccentric hypertrophy in HFrEF and concentric hypertrophy in HFpEF. Patients with diabetes mellitus had lower Kansas City Cardiomyopathy Questionnaire scores in both HFpEF and HFrEF, with more prominent differences in HFpEF (Pinteraction<0.05). In both HFpEF and HFrEF, patients with diabetes mellitus had more HF rehospitalizations (adjusted hazard ratio, 1.27; 95% CI, 1.05-1.54; P=0.014) and higher 1-year rates of the composite of all-cause mortality/HF hospitalization (adjusted hazard ratio, 1.22; 95% CI, 1.05-1.41; P=0.011), with no differences between HF phenotypes (Pinteraction>0.05). Conclusions In HFpEF and HFrEF, type 2 diabetes mellitus is associated with smaller left ventricular volumes, higher mitral E/e' ratio, poorer quality of life, and worse outcomes, with several differences noted between HF phenotypes. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01633398.

3.
Diabetes Care ; 42(9): 1792-1799, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31292141

RESUMO

OBJECTIVE: Microvascular complications are common among patients with diabetes mellitus (DM). The presence of heart failure (HF) is presumed to be due to macrovascular disease (typically HF with reduced ejection fraction [HFrEF] following myocardial infarction). We hypothesized that HF with preserved ejection fraction (HFpEF) in patients with DM may be a manifestation of microvascular disease compared with HFrEF. The objective of this study was to examine the prevalence and association with clinical outcome of microvascular complications in patients with HF and DM. RESEARCH DESIGN AND METHODS: We investigated the prevalence, association with clinical outcome, and cardiac structure and function of microvascular (neuropathy, nephropathy, and retinopathy) complications of DM in 2,800 prospectively enrolled participants with HF and DM (561 with HFpEF) from the Asian Sudden Cardiac Death In Heart Failure (ASIAN-HF) registry. RESULTS: A total of 601 (21.5%) participants with DM had microvascular complications. Participants with DM and any (one or more) microvascular complications were more likely to have HFpEF (odds ratio 1.70 [95% CI 1.15-2.50]; P = 0.008). Furthermore, the likelihood of having HFpEF increased with an increasing number of microvascular complications (P trend < 0.001). Microvascular complications were associated with more left ventricular (LV) hypertrophy and a greater reduction in quality of life in HFpEF than HFrEF (P interaction < 0.001 for all). Compared with participants with DM and without microvascular complications, the adjusted hazard ratio for the composite outcome of all-cause death or HF hospitalization was 1.35 (95% CI 1.04-1.76) for participants with DM and microvascular complications regardless of HF type (P interaction = 0.112). CONCLUSIONS: Diabetic microvascular disease is more common, and related to greater LV remodeling, more impairment of quality in life, and similar adverse outcomes, in participants with HFpEF compared with HFrEF. HFpEF may be a clinical manifestation of microvascular disease in DM.

4.
Heart ; 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337669

RESUMO

OBJECTIVES: High-sensitivity cardiac troponin testing is used in the diagnosis of acute coronary syndromes but its role during convalescence is unknown. We investigated the long-term prognostic significance of serial convalescent high-sensitivity cardiac troponin concentrations following acute coronary syndrome. METHODS: In a prospective multicentre observational cohort study of 2140 patients with acute coronary syndrome, cardiac troponin I concentrations were measured in 1776 patients at 4 and 12 months following the index event. Patients were stratified into three groups according to the troponin concentration at 4 months using the 99th centile (women>16 ng/L, men>34 ng/L) and median concentration of those within the reference range. The primary outcome was cardiovascular death. RESULTS: Troponin concentrations at 4 months were measurable in 99.0% (1759/1776) of patients (67±12 years, 72% male), and were ≤5 ng/L (median) and >99th centile in 44.8% (795) and 9.3% (166), respectively. There were 202 (11.4%) cardiovascular deaths after a median of 4.8 years. After adjusting for the Global Registry of Acute Coronary Events score, troponin remained an independent predictor of cardiovascular death (HR 1.4, 95% CI 1.3 to 1.5 per doubling) with the highest risk observed in those with increasing concentrations at 12 months. Patients with 4-month troponin concentrations >99th centile were at increased risk of cardiovascular death compared with those ≤5 ng/L (29.5% (49/166) vs 4.3% (34/795); adjusted HR 4.9, 95% CI 3.8 to 23.7). CONCLUSIONS: Convalescent cardiac troponin concentrations predict long-term cardiovascular death following acute coronary syndrome. Recognising this risk by monitoring troponin may improve targeting of therapeutic interventions. TRIAL REGISTRATION NUMBER: ACTRN12605000431628;Results.

5.
Arthritis Rheumatol ; 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31162825

RESUMO

OBJECTIVE: To determine whether gout and serum urate (SU) levels are associated with increased risk of death, time to first readmission for any cardiovascular event, or incident heart failure in individuals with cardiovascular disease. METHODS: Individuals presenting with an acute coronary syndrome (ACS) were enrolled in the Coronary Disease Cohort Study. Clinical data were collected from the medical records at the index hospital admission, and clinical, echocardiographic, and biochemical data were collected postdischarge. Gout was defined by self-report, use of urate-lowering therapy, or use of colchicine with evidence of gout on review of the medical record. The primary end points were all-cause mortality, time to readmission for a cardiac ischemic event, and time to readmission for heart failure. RESULTS: Data from 1,514 participants were available. During the follow-up period, 53 of 160 participants with gout (33.1%) and 298 of 1,354 participants without gout (22.0%) died. After adjustment for other factors known to be associated with mortality, there was no gout-specific increase in risk of mortality (adjusted hazard ratio 0.98 [95% confidence interval 0.69-1.38]). Time to readmission for heart failure was significantly briefer in those with, compared to those without, gout (adjusted hazard ratio 1.42 [95% confidence interval 1.02-1.97]). Irrespective of whether a participant had gout or not, as SU level increased, there was an increased risk of death and readmission for either a cardiovascular event or heart failure. CONCLUSION: Survival post-ACS is similar with and without the presence of gout. People with gout are at an increased risk of readmission for heart failure and have longer hospital stays. Risk of these events increases in parallel with increases in SU levels.

6.
Clin Chem ; 65(9): 1115-1124, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31092393

RESUMO

BACKGROUND: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Plasma concentrations of B-type natriuretic peptide (BNP) or its amino terminal congener (NT-proBNP) are used for HF diagnosis and risk stratification. Because BNP concentrations are inexplicably lowered in obese patients, we investigated the relationship between proBNP glycosylation, plasma NT-proBNP, and body mass index (BMI) in HF patients. METHODS: Three assays were developed to distinguish between total proBNP (glycosylated plus nonglycosylated proBNP), proBNP not glycosylated at threonine 71 (NG-T71), and proBNP not glycosylated in the central region (NG-C). Intraassay and interassay CVs were <15%; limits of detection were <21 ng/L; and samples diluted in parallel. RESULT: Applying these assays and an NT-proBNP assay to plasma samples from 106 healthy volunteers and 238 HF patients determined that concentrations [median (interquartile range)] of proBNP, NG-T71, and NT-proBNP were greater in HF patients compared with controls [300 (44-664), 114 (18-254), and 179 (880-3459) ng/L vs 36 (18-229), 36 (18-175), and 40 (17-68) ng/L, respectively; all P < 0.012]. NG-C was undetectable in most samples. ProBNP concentrations in HF patients with BMI more or less than 30 kg/m2 were not different (P = 0.85), whereas HF patients with BMI >30 kg/m2 had lower NT-proBNP and NG-T71 concentrations (P < 0.003) and higher proBNP/NT-proBNP and proBNP/NG-T71 ratios (P = 0.001 and P = 0.02, respectively) than those with BMI <30 kg/m2. CONCLUSIONS: Increased BMI is associated with decreased concentrations of proBNP not glycosylated at T71. Decreased proBNP substrate amenable to processing could partially explain the lower NT-proBNP and BNP concentrations observed in obese individuals, including those presenting with HF.

7.
Ageing Res Rev ; 53: 100909, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31116994

RESUMO

Aging influences the pathogenesis and progression of several major diseases affecting both the cardiovascular system (CVS) and central nervous system (CNS). Defining the common molecular features that underpin these disorders in these crucial body systems will likely lead to increased quality of life and improved 'health-span' in the global aging population. Degenerative protein modifications (DPMs) have been strongly implicated in the molecular pathogenesis of several age-related diseases affecting the CVS and CNS, including atherosclerosis, heart disease, dementia syndromes, and stroke. However, these isolated findings have yet to be integrated into a wider framework, which considers the possibility that, despite their distinct features, CVS and CNS disorders may in fact be closely related phenomena. In this work, we review the current literature describing molecular roles of the major age-associated DPMs thought to significantly impact on human health, including carbamylation, citrullination and deamidation. In particular, we focus on data indicating that specific DPMs are shared between multiple age-related diseases in both CVS and CNS settings. By contextualizing these data, we aim to assist future studies in defining the universal mechanisms that underpin both vascular and neurological manifestations of age-related protein degeneration.

8.
Clin Biochem ; 69: 36-44, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129182

RESUMO

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is an emerging marker of cardiovascular disease burden. Appropriate assessment of assay performance and reference interval are required to enable interpretation of results to facilitate its clinical application. METHODS: suPAR was measured using the suPARnostic® ELISA in 155 healthy volunteers. Assay performance was assessed for anticoagulant effect, recovery, interference, linearity and cross-reactivity. The identity of immunoreactive suPAR was confirmed by size-exclusion HPLC. To establish anatomical sites of release and uptake, we measured suPAR in regional samples from subjects undergoing cardiac catheterization. RESULTS: The median concentration of suPAR was 2.1 ng/mL (IQR:1.7-2.3) in health. In comparison with EDTA, suPAR measurements were affected by lithium heparin (>10% change) and increased with serum usage. suPAR reactivity also increased in the presence of haemolysis (10 g/L), but was suppressed with urokinase and lipids (4 g/L). In multiple regression analyses, suPAR associated independently with body weight, NT-proBNP and MR-proADM (P = .03) for healthy individuals. Regional plasma sampling showed lower suPAR concentrations in the coronary sinus and renal vein compared with concentrations in femoral arterial samples. Immunoreactive circulating suPAR species had Mr of 10-39 kDa. CONCLUSION: The suPARnostic® assay performs acceptably for a clinical assay but is limited in the presence of high levels of hemolysis, lipids and urokinase. We provide the first evidence for the heart and kidneys as organs of suPAR clearance in humans. Additional investigations are warranted to determine whether there is a need to compare the marker performance of differing circulating forms of suPAR.


Assuntos
Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Adulto , Cromatografia em Gel/métodos , Cromatografia Líquida de Alta Pressão/métodos , Ensaio de Imunoadsorção Enzimática , Feminino , Voluntários Saudáveis , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Peso Molecular , Receptores de Ativador de Plasminogênio Tipo Uroquinase/química , Padrões de Referência
10.
11.
Eur J Heart Fail ; 21(3): 297-307, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30548089

RESUMO

AIMS: To examine sex differences in clinical characteristics, echocardiographic features, quality of life and 1-year death or heart failure (HF) hospitalization outcomes in patients with/without diabetes mellitus (DM). METHODS AND RESULTS: Utilizing the Asian Sudden Cardiac Death in HF (ASIAN-HF) registry, 5255 patients (mean age 59.6 ± 13.1, 78% men) with symptomatic HF with reduced ejection fraction (HFrEF) were stratified by DM status to address the research aims. Despite similar prevalence of DM between Asian men (43%) and women (42%), the odds of DM increased at lower body mass index in women vs. men (≥ 23 vs. ≥ 27.5 kg/m2 , Pinteraction = 0.014). DM was more strongly related to chronic kidney disease in women vs. men [adjusted odds ratio (OR) 1.85, 95% confidence interval (CI) 1.33-2.57 vs. OR 1.32, 95% CI 1.11-1.56, Pinteraction = 0.009]. Sex also modified the relationship between DM and left ventricular geometry (Pinteraction = 0.003), whereby DM was associated with a more concentric left ventricular geometry in women than men. Women had lower quality of life than men (P < 0.001), in both DM and non-DM groups. DM was associated with worse composite outcomes at 1 year in women vs. men [hazard ratio (HR) 1.79, 95% CI 1.24-2.60 vs. HR 1.32, 95% CI 1.12-1.56; Pinteraction = 0.005). CONCLUSIONS: Asian women with HFrEF were more likely to have DM despite a lean body mass index, a greater burden of chronic kidney disease and more concentric left ventricular geometry, compared to men. Furthermore, DM confers worse quality of life, irrespective of sex, and a greater risk of adverse outcomes in women than men. These data underscore the need for sex-specific approaches to diabetes in patients with HF.

12.
Circulation ; 138(24): 2763-2773, 2018 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-30565987

RESUMO

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF), traditionally considered a disease of the elderly, may also affect younger patients. However, little is known about HFpEF in the young. METHODS: We prospectively enrolled 1203 patients with HFpEF (left ventricular ejection fraction ≥50%) from 11 Asian regions. We grouped HFpEF patients into very young (<55 years of age; n=157), young (55-64 years of age; n=284), older (65-74 years of age; n=355), and elderly (≥75 years of age; n=407) and compared clinical and echocardiographic characteristics, quality of life, and outcomes across age groups and between very young individuals with HFpEF and age- and sex-matched control subjects without heart failure. RESULTS: Thirty-seven percent of our HFpEF population was <65 years of age. Younger age was associated with male preponderance and a higher prevalence of obesity (body mass index ≥30 kg/m2; 36% in very young HFpEF versus 16% in elderly) together with less renal impairment, atrial fibrillation, and hypertension (all P<0.001). Left ventricular filling pressures and prevalence of left ventricular hypertrophy were similar in very young and elderly HFpEF. Quality of life was better and death and heart failure hospitalization at 1 year occurred less frequently ( P<0.001) in the very young (7%) compared with elderly (21%) HFpEF. Compared with control subjects, very young HFpEF had a 3-fold higher death rate and twice the prevalence of hypertrophy. CONCLUSIONS: Young and very young patients with HFpEF display similar adverse cardiac remodeling compared with their older counterparts and very poor outcomes compared with control subjects without heart failure. Obesity may be a major driver of HFpEF in a high proportion of HFpEF in the young and very young.

13.
J Am Coll Cardiol ; 72(19): 2321-2323, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30384888
14.
J Clin Sleep Med ; 14(10): 1773-1781, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30353816

RESUMO

STUDY OBJECTIVES: Sleep apnea is often newly diagnosed in patients presenting with ST-segment elevation myocardial infarction (STEMI). We assessed longitudinal changes in apnea-hypopnea index (AHI) and sleep apnea phenotype after STEMI and determined its association with changes in the left ventricular ejection fraction (LVEF). METHODS: A total of 101 eligible patients with STEMI underwent consecutive sleep studies and echocardiographic studies within 5 days of admission and at 6-month follow-up. Sleep apnea (AHI ≥ 15 events/h) was further divided into obstructive sleep apnea (OSA) or central sleep apnea (CSA). RESULTS: Both AHI (mean difference -6.4 events/h, 95% confidence interval [CI] -9.6 to 3.3, P < .001) and LVEF (mean difference 2.6%, 95% CI 1.3 to 4.0, P < .001) improved from baseline to 6 months. The improvement in AHI was associated with an increase in LVEF (ß = -.47, 95% CI -.86 to -.07, P = .023) and a decrease in left ventricular end-systolic volume (LVESV) (ß = .25, 95% CI .07 to .43, P = .007). Of the patients with OSA at baseline (46%), resolution of OSA was seen in 48% at 6 months. Of those with CSA at baseline (12%), conversion to OSA was seen in 83%. In contrast, among those with no sleep apnea (42%) at baseline, the diagnosis remained the same in 93% at 6 months. CONCLUSIONS: Concurrent changes in AHI, LVEF, and LVESV were seen after STEMI. Sleep studies performed on admission are reliable in excluding sleep apnea. However, patients with OSA or CSA on admission warrant re-evaluation due to evolution of the sleep apnea phenotype.

15.
Circ Cardiovasc Qual Outcomes ; 11(8): e004699, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30354372

RESUMO

Background Expediting reperfusion during primary percutaneous coronary intervention is aimed at salvaging myocardium in ST-segment-elevation myocardial infarction. Few studies have examined the relation between reperfusion time and heart failure (HF) events. Methods and Results: We studied 7597 patients undergoing primary percutaneous coronary intervention from 2007 to 2013 in the Singapore Myocardial Infarct Registry, which captures HF at admission, postadmission in-hospital HF, and HF rehospitalization. We studied the relation of first medical contact to deployment of first device to achieve reperfusion (FTD) time with in-hospital HF events and HF rehospitalization, with mortality modeled as a competing risk. At the population level, median FTD time decreased from 91 minutes (interquartile range, 69-114) in 2007 to 58 minutes (45-75) in 2013 ( P=0.001), whereas mortality remained unchanged (in-hospital: range 5.3%-7.3%; P=0.190 and 1-year: range 7.8%-10.9%; P=0.505). HF at admission increased from 12.2% in 2007 to 18.4% in 2013, P=0.020, whereas postadmission in-hospital HF decreased from 12.8% in 2007 to 7.1% in 2013, P=0.030. HF rehospitalization increased from 1.2% in 2007 to 2.6% in 2013 ( P=0.003), for 30-day HF rehospitalization, and 3.8% in 2007 to 5.6% in 2013 ( P=0.037), for 1-year HF rehospitalization. At the individual level, among patients with HF at admission (N=1191), longer FTD time was associated with more 30-day HF rehospitalization (compared with ≤60 minutes, adjusted hazard ratio, 1.68 [0.73-3.86] for 60-90 minutes, 2.88 [1.19-6.92], for 90-120 minutes, and 2.84 [1.08-7.44] for >120 minutes). Longer FTD time was associated with a greater risk of postadmission in-hospital HF (compared with ≤60 minutes, adjusted hazard ratio, 1.18 [0.96-1.44] for 60-90 minutes, 1.59 [1.25-2.03] for 90-120 minutes, and 1.67 [1.26-2.21] for >120 minutes). Conclusions: Temporal reductions in FTD time were associated with decrease in postadmission in-hospital HF. Among patients presenting with HF at admission, delays in FTD beyond 90 minutes were associated with more 30-day HF rehospitalization.

16.
JAMA Cardiol ; 3(11): 1108-1112, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30347004

RESUMO

Importance: Emergency department (ED) investigations of patients with suspected acute myocardial infarction (AMI) are time consuming, partly because of the turnaround time of laboratory tests. Current point-of-care troponin assays shorten test turnaround times but lack precision at lower concentrations. Development of point-of-care troponin assays with greater analytical precision could reduce the decision-making time in EDs for ruling out AMI. Objective: To determine the clinical accuracy for AMI of a single troponin concentration measured on arrival to ED with a new-generation, higher precision point-of-care assay with a 15-minute turnaround time. Design, Setting, and Participants: This observational study occurred at a single urban regional ED. Adults presenting acutely from the community to the ED with symptoms suggestive of AMI were included. Troponin concentrations were measured on ED arrival with both a novel point-of-care assay (i-STAT TnI-Nx; Abbott Point of Care) and a high-sensitivity troponin I assay (Architect hs-cTnI; Abbott Diagnostics). Main Outcomes and Measures: The primary outcome was type 1 AMI during index presentation. We compared the discrimination ability of the TnI-Nx assay with the hs-cTnI assay using the area under receiver operator characteristic curve (AUC) and sensitivity, negative predictive value, and the proportion of negative test results at thresholds with 100% sensitivity. Results: Of 354 patients (255 [72.0%] men; mean [SD] age, 62 [12] years), 57 (16.1%) experienced an AMI. Eighty-five patients (24.0%) presented to the ED less than 3 hours after symptom onset. No difference was found between the AUC of the TnI-Nx assay (0.975 [95% CI, 0.958-0.993]) and the hs-cTnI assay (0.970 [95% CI, 0.949 to 0.990]; P = .46). A TnI-Nx assay result of less than 11 ng/L identified 201 patients (56.7%) as low risk, with a sensitivity of 100% (95% CI, 93.7%-100%) and a negative predictive value of 100% (95% CI, 98.2%-100%). In comparison, an hs-cTnI assay result of less than 3 ng/L identified 154 patients (43.5%) as low risk, with a sensitivity of 100% (95% CI, 93.7%-100%) and a negative predictive value of 100% (95% CI, 97.6%-100%). Conclusions and Relevance: A novel point-of-care troponin assay that can produce a result 15 minutes after blood sampling had comparable discrimination ability to an hs-cTnI assay for ruling out AMI after a single blood test. Use in the ED may facilitate earlier decision making and could expedite the safe discharge of a large proportion of low-risk patients.

17.
Nat Rev Cardiol ; 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30323278
18.
Biosci Rep ; 38(5)2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-30206134

RESUMO

While it is well established that centrally injected angiotensin II (Ang II) has potent actions on sympathetic nervous activity (SNA), it is less clear whether peripheral Ang II can immediately stimulate SNA. In particular, the contribution of cardiac sympathetic nerve activity (CSNA) to the acute pressor response is unknown. We therefore examined the effect of incremental doses of intravenous Ang II (3, 6, 12, 24, and 48 ng/kg/min each for 30 min) on CSNA in eight conscious sheep. Ang II infusions progressively increased plasma Ang II up to 50 pmol/l above control levels in dose-dependent fashion (P<0.001). This was associated with the expected increases in mean arterial pressure (MAP) above control levels from <10 mmHg at lower doses up to 23 mmHg at the highest dose (P<0.001). Heart rate and cardiac output fell progressively with each incremental Ang II infusion achieving significance at higher doses (P<0.001). There was no significant change in plasma catecholamines. At no dose did Ang II increase any of the CSNA parameters measured. Rather, CSNA burst frequency (P<0.001), burst incidence, (P=0.002), and burst area (P=0.004) progressively decreased achieving significance during the three highest doses. In conclusion, Ang II infused at physiologically relevant doses increased MAP in association with a reciprocal decrease in CSNA presumably via baroreceptor-mediated pathways. The present study provides no evidence that even low-dose systemic Ang II stimulates sympathetic traffic directed to the heart, in normal conscious sheep.

19.
Lancet Glob Health ; 6(9): e1008-e1018, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30103979

RESUMO

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), ß blockers, and mineralocorticoid receptor antagonists (MRAs) are of proven benefit and are recommended by guidelines for management of patients with heart failure and reduced ejection fraction (HFrEF). We aimed to examine the first prospective multinational data from Asia on prescribing patterns of guideline-directed medical therapies and analyse its effect on outcomes. METHODS: In the prospective multinational ASIAN-HF registry (with enrolment from 46 centres in 11 countries in Asia), we enrolled patients aged 18 years or older, with symptomatic heart failure (stage C, with at least one episode of decompensated heart failure in the past 6 months that resulted in admission to hospital or was treated in an outpatient clinic) and left ventricular systolic dysfunction (ejection fraction ≤40% on baseline echocardiography, consistent with 2016 European Society of Cardiology guidelines). We excluded patients with heart failure caused by severe valvular heart disease, life-threatening comorbidity with a life expectancy of less than 1 year, who were unable or unwilling to give consent, or who had concurrent participation in a clinical trial. Patients were followed up for 3 years for the outcomes of death and cause-specific admittance to hospital. Primary outcomes were uptake of guideline-directed medical therapies (as proportions) by therapeutic class, achieved doses as proportions of guideline-recommended doses, and their association with 1-year composite outcome of all-cause death or admittance to hospital because of heart failure. This study is registered with ClinicalTrials.gov, number NCT01633398. FINDINGS: Between Oct 1, 2012, and Dec 31, 2015, we enrolled 5276 patients with HFrEF (mean age 59·6 years [SD 13·2], 77% men, body-mass index 24·9 kg/m2 [5·1], 33% New York Heart Association class III or IV). Follow-up data were available for 4544 (90%) of 5061 eligible patients taking medication for heart failure, with median follow-up of 417 days (IQR 214-735). ACE inhibitors or ARBs were prescribed to 3868 (77%) of 5005 patients, ß blockers to 3975 (79%) of 5061, and MRAs to 2998 (58%) of 5205, with substantial regional variation. Guideline-recommended dose was achieved in only 17% of cases for ACE inhibitors or ARB, 13% for ß blockers, and 29% for MRAs. Country (all three drug classes), increasing body-mass index (ACE inhibitors or ARBs and MRAs), and in-patient recruitment (ACE inhibitors or ARBs and ß blockers) were associated with attainment of guideline-recommended dose (all p<0·05). When adjusted for indication bias, increasing drug doses, from low dose (1-<25% of guideline-recommended dose) upwards were associated with lower hazards of a 1-year composite outcome for ACE inhibitors or ARBs and ß blockers compared with non-users. The lowest adjusted hazards were in the group that attained guideline-recommended doses above 50% (hazard ratio [HR] 0·54, 95% CI 0·50-0·58 for ACE inhibitors or ARBs [50-99·9%]; HR 0·47, 0·46-0·50 for ß blockers, and HR 0·77, 0·72-0·81 for MRAs [≥100%]). INTERPRETATION: Guideline-directed medical therapies at recommended doses are underutilised in patients with HFrEF. Improved uptake and uptitration of guideline-directed medical therapies are needed for better patient outcomes. FUNDING: National Medical Research Council (Singapore), A*STAR Biomedical Research Council ATTRaCT program, Boston Scientific Investigator Sponsored Research program, and Bayer.

20.
BMC Cardiovasc Disord ; 18(1): 169, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30111293

RESUMO

BACKGROUND: Development of collateral circulation in coronary artery disease is cardio-protective. A key process in forming new blood vessels is attraction to occluded arteries of monocytes with their subsequent activation as macrophages. In patients from a prospectively recruited post-acute coronary syndromes cohort we investigated the prognostic performance of three products of activated macrophages, soluble vascular endothelial growth factor (VEGF) receptors (sFlt-1 and sKDR) and pterins, alongside genetic variants in VEGF receptor genes, VEGFR-1 and VEGFR-2. METHODS: Baseline levels of sFlt-1 (VEGFR1), sKDR (VEGFR2) and pterins were measured in plasma samples from subgroups (n = 513; 211; 144, respectively) of the Coronary Disease Cohort Study (CDCS, n = 2067). DNA samples from the cohort were genotyped for polymorphisms from the VEGFR-1 gene SNPs (rs748252 n = 2027, rs9513070 n = 2048) and VEGFR-2 gene SNPs (rs2071559 n = 2050, rs2305948 n = 2066, rs1870377 n = 2042). RESULTS: At baseline, levels of sFlt-1 were significantly correlated with age, alcohol consumption, NTproBNP, BNP and other covariates relevant to cardiovascular pathophysiology. Total neopterin levels were associated with alcohol consumption at baseline. 7,8 dihydroneopterin was associated with BMI. The A allele of VEGFR-2 variant rs1870377 was associated with higher plasma sFlt-1 and lower levels of sKDR at baseline. Baseline plasma sFlt-1 was univariately associated with all cause mortality with (p < 0.001) and in a Cox's proportional hazards regression model sFlt-1 and pterins were both associated with mortality independent of established predictors (p < 0.027). CONCLUSIONS: sFlt-1 and pterins may have potential as prognostic biomarkers in acute coronary syndromes patients. Genetic markers from VEGF system genes warrant further investigation as markers of levels of VEGF system components in these patients. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry. ACTRN12605000431628 . 16 September 2005, Retrospectively registered.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA