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ABSTRACT: B-type natriuretic peptide (BNP) is a prognostic and diagnostic marker for heart failure (HF). An anti-inflammatory, cardio-protective role for BNP was proposed. In cardiovascular diseases including pressure overload-induced HF, perivascular inflammation and cardiac fibrosis are, in part, mediated by monocyte chemoattractant protein (MCP)1-driven monocyte migration. We aimed to determine the role of BNP in monocyte motility to MCP1. A functional BNP receptor, natriuretic peptide receptor-A (NPRA) was identified in human monocytes. BNP treatment inhibited MCP1-induced THP1 (monocytic leukemia cells) and primary monocyte chemotaxis (70 and 50 %, respectively). BNP did not interfere with MCP1 receptor expression or with calcium. BNP inhibited activation of the cytoskeletal protein RhoA in MCP1-stimulated THP1 (70 %). Finally, BNP failed to inhibit MCP1-directed motility of monocytes from patients with hypertension (n = 10) and HF (n = 6) suggesting attenuation of this anti-inflammatory mechanism in chronic heart disease. We provide novel evidence for a direct role of BNP/NPRA in opposing human monocyte migration and support a role for BNP as a cardio-protective hormone up-regulated as part of an adaptive compensatory response to combat excess inflammation.
Journal of Cardiovascular Translational Research 04/2013; · 2.61 Impact Factor
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ABSTRACT: Mechanical overload of the heart is associated with excessive deposition of extracellular matrix proteins and the development of cardiac fibrosis. This can result in reduced ventricular compliance, diastolic dysfunction, and heart failure. Extracellular matrix synthesis is regulated primarily by cardiac fibroblasts, more specifically, the active myofibroblast. The influence of mechanical stretch on human cardiac fibroblasts' response to pro-fibrotic stimuli, such as transforming growth factor beta (TGFβ), is unknown as is the impact of stretch on B-type natriuretic peptide (BNP) and natriuretic peptide receptor A (NPRA) expression. BNP, acting via NPRA, has been shown to play a role in modulation of cardiac fibrosis.
The effect of cyclical mechanical stretch on TGFβ induction of myofibroblast differentiation in primary human cardiac fibroblasts and whether differences in response to stretch were associated with changes in the natriuretic peptide system were investigated. Cyclical mechanical stretch attenuated the effectiveness of TGFβ in inducing myofibroblast differentiation. This finding was associated with a novel observation that mechanical stretch can increase BNP and NPRA expression in human cardiac fibroblasts, which could have important implications in modulating myocardial fibrosis. Exogenous BNP treatment further reduced the potency of TGFβ on mechanically stretched fibroblasts.
We postulate that stretch induced up-regulation of the natriuretic peptide system may contribute to the observed reduction in myofibroblast differentiation.
Fibrogenesis & Tissue Repair 07/2012; 5(1):9.
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ABSTRACT: In asymptomatic subjects B-type natriuretic peptide (BNP) is associated with adverse cardiovascular outcomes even at levels well below contemporary thresholds used for the diagnosis of heart failure. The mechanisms behind these observations are unclear. We examined the hypothesis that in an asymptomatic hypertensive population BNP would be associated with sub-clinical evidence of cardiac remodeling, inflammation and extracellular matrix (ECM) alterations. We performed transthoracic echocardiography and sampled coronary sinus (CS) and peripheral serum from patients with low (n = 14) and high BNP (n = 27). Peripheral BNP was closely associated with CS levels (r = 0.92, p<0.001). CS BNP correlated significantly with CS levels of markers of collagen type I and III turnover including: PINP (r = 0.44, p = 0.008), CITP (r = 0.35, p = 0.03) and PIIINP (r = 0.35, p = 0.001), and with CS levels of inflammatory cytokines including: TNF-α (r = 0.49, p = 0.002), IL-6 (r = 0.35, p = 0.04), and IL-8 (r = 0.54, p<0.001). The high BNP group had greater CS expression of fibro-inflammatory biomarkers including: CITP (3.8±0.7 versus 5.1±1.9, p = 0.007), TNF-α (3.2±0.5 versus 3.7±1.1, p = 003), IL-6 (1.9±1.3 versus 3.4±2.7, p = 0.02) and hsCRP (1.2±1.1 versus 2.4±1.1, p = 0.04), and greater left ventricular mass index (97±20 versus 118±26 g/m(2), p = 0.03) and left atrial volume index (18±2 versus 21±4, p = 0.008). Our data provide insight into the mechanisms behind the observed negative prognostic impact of modest elevations in BNP and suggest that in an asymptomatic hypertensive cohort a peripheral BNP measurement may be a useful marker of an early, sub-clinical pathological process characterized by cardiac remodeling, inflammation and ECM alterations.
PLoS ONE 01/2012; 7(11):e49259. · 4.09 Impact Factor
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ABSTRACT: The role of statin therapy in heart failure (HF) is unclear. The amino-terminal propeptide of procollagen type III (PIIINP) predicts outcome in HF, and yet there are conflicting reports of statin therapy effects on PIIINP.
This study determined whether there was an increase in serum markers of inflammation, fibrosis (including PIIINP), and B-type natriuretic peptide (BNP) in patients with systolic HF and normal total cholesterol and determined the effects of long-term treatment with atorvastatin on these markers.
Fifty-six white patients with systolic HF and normal cholesterol levels (age 72 [13] years; 68% male; body mass index 27.0 [7.3] kg/m(2); ejection fraction 35 [13]%; 46% with history of smoking) were randomly allocated to atorvastatin treatment for 6 months, titrated to 40 mg/d (A group) or not (C group). Age- and/or sex-matched subjects without HF (N group) were also recruited. Biomarkers were measured at baseline (all groups) and 6 months (A and C groups).
Serum markers of collagen turnover, inflammation, and BNP were significantly elevated in HF patients compared with normal participants (all P < 0.05). There were correlations between these markers in HF patients but not in normal subjects. Atorvastatin treatment for 6 months caused a significant reduction in the following biomarkers compared with baseline: BNP, from median (interquartile range) 268 (190-441) pg/mL to 185 (144-344) pg/mL; high-sensitivity C-reactive protein (hs-CRP), from 5.26 (1.95 -9.29) mg/L to 3.70 (2.34-6.81) mg/L; and PIIINP, from 4.65 (1.86) to 4.09 (1.25) pg/mL (all P < 0.05 baseline vs 6 months). Between-group differences were significant for PIIINP only (P = 0.027). There was a positive interaction between atorvastatin effects and baseline hs-CRP and PIIINP (P < 0.01).
Long-term statin therapy reduced PIIINP in this small, selected HF population with elevated baseline levels. Further evaluation of statin therapy in the management of HF patients with elevated PIIINP is warranted.
Clinical Therapeutics 12/2011; 34(1):91-100. · 2.32 Impact Factor
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ABSTRACT: Improvements in the control of LDL-C levels have occurred in the past decade due to the introduction of increasingly potent statins, such as atorvastatin and rosuvastatin. Many patients, however, do not achieve their LDL-C goals, which presents a practical dilemma for clinicians and highlights the need to identify adherence problems in a clinically relevant manner.
The purpose of this study was to evaluate the relationship between LDL-C goal achievement and both medication adherence and beliefs assessed using structured questioning.
All patients were aged ≥40 years and participated in the cardiovascular risk factor management program STOP-HF (St. Vincent's Screening To Prevent Heart Failure study). One hundred and eighty-five participants who had been prescribed statins, split between those who achieved and those who did not achieve LDL-C goal, were randomly selected for a prospective study examining the relationship between adherence, assessed by the Morisky Medication Adherence Scale (MMAS), and LDL-C goal achievement. Patients' beliefs about medicines were assessed using the Beliefs about Medicines Questionnaire-General (BMQ-G). Main outcome measures were predictors of LDL-C goal achievement and medication adherence and predictors of adherence among patients using the MMAS.
The average age of the selected patients was 64.9 (9.9) years; 45% were male, 46% had hypertension, 17.5% had coronary artery disease, and 10% had diabetes. Questionnaires were answered by 119 patients, 71 of whom (59.7%) were goal achievers. LDL-C goal achievers were more likely to respond to the questionnaires than nonachievers (76.8% vs 52.7%; P = 0.002). Fifty-eight respondents (48.7%) reported that they were not fully adherent to medication and in multivariable analysis were twice as likely to miss LDL-C goal compared with those who were adherent. Approximately 25% of patients who reported nonadherence were intentionally so. Patients' beliefs about medicines were a significant predictor of self-reported adherence but not of LDL-C goal achievement.
Medication nonadherence may be responsible for failure to achieve goal in many patients who are prescribed statins. In routine clinical care, the structured MMAS questionnaire may provide clinicians with an effective tool to assess medication nonadherence in the context of statin therapy failure. STOP-HF ClinicalTrials.gov identifier: NCT00921960.
Clinical Therapeutics 08/2011; 33(9):1180-9. · 2.32 Impact Factor
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ABSTRACT: Previous large-scale, retrospective studies have shown increased mortality in heart failure (HF) patients using β2-agonists (B2As). We further examined the relationship between B2A use and mortality in a well-characterized population by adjusting for natriuretic peptide levels as a measure of HF severity.
This was a retrospective cohort study of patients attending an HF Disease Management Programme with mean follow-up of 2.9 ± 2.4 years. Chart review confirmed B2A use, dose and duration of use, and documented pulmonary function evaluation. The primary endpoint was the effect of B2A use compared with no B2A use on mortality using unadjusted and adjusted Kaplan-Meier survival curves. Data were available for 1294 patients (age 70.6 ± 11.5 years) of whom 64% were male and 22.2% were taking B2As. β2-Agonist users were older, more likely to be male, to have smoked, to have chronic obstructive pulmonary disease (COPD) and asthma, and less likely to take beta-blockers. Multivariable associates of mortality included: B-type natriuretic peptide (BNP), coronary artery disease, age, and beta-blocker use. Unadjusted mortality rates for B2A users were found to be significantly higher than non-B2A users [hazard ratio (HR) 1.304, 95% confidence interval (CI) 1.030-1.652, P= 0.028]. However, when adjusted for age, sex, medication, co-morbidity, smoking, COPD, and BNP differences, overall mortality rates were similar [HR 1.043, 95% CI (0.771-1.412), P= 0.783].
Unlike previous reports, this retrospective evaluation of B2A therapy in HF patients shows no relationship with long-term mortality when adjusted for population differences including BNP. Large, prospective studies are required to define the risk/benefit ratio of B2As in patients with heart failure.
European Journal of Heart Failure 08/2011; 13(8):885-91. · 4.90 Impact Factor
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ABSTRACT: An effective prevention strategy for heart failure in primary care requires a reliable screening tool for asymptomatic ventricular dysfunction. Preliminary data indicate that B-type natriuretic peptide (BNP) may be suitable for this task. However, for the most effective use of this peptide, the interrelationships between associated risk factors and their therapies on BNP, and in particular their magnitude of effect, needs to be established in a large primary care population. Therefore, the objective of the study was to establish the extent of the association between BNP, cardiovascular risk factors and their therapies.
BNP measurement and clinical review was preformed on 1122 primary care patients with cardiovascular risk factors. Multivariate analyses identified significant associates of BNP concentrations which were further explored to establish the magnitude of their association.
Associates of BNP were age (1.36-fold increase in BNP/decade), female (1.28), β-blockers (1.90), myocardial infarction (1.36), arrhythmia (1.98), diastolic blood pressure; all p<0.01. A novel method was devised that plotted median BNP per sliding decade of age for the various combinations of these principal associates.
The data presented underline the importance of considering several clinical and therapeutic factors when interpreting BNP concentrations. Most of these variables were associated with increased concentrations, which may in part explain the observed false-positive rates for detecting ventricular dysfunction using this peptide. Furthermore, the design of studies or protocols using BNP as an endpoint or a clinical tool should take particular account of these associations. This analysis provides the foundation for age, risk factor and therapy adjusted reference ranges for BNP in this setting.
Clinical Chemistry and Laboratory Medicine 01/2011; 49(4):719-28. · 2.15 Impact Factor
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ABSTRACT: Heart failure with preserved ejection fraction (HF-PEF) can be difficult to diagnose in clinical practice. Myocardial fibrosis is a major determinant of diastolic dysfunction (DD), potentially contributing to the progression of HF-PEF. The aim of this study was to analyse whether serological markers of collagen turnover may predict HF-PEF and DD.
We included 85 Caucasian treated hypertensive patients (DD n=65; both DD and HF-PEF n=32). Serum carboxy (PICP), amino (PINP), and carboxytelo (CITP) peptides of procollagen type I, amino (PIIINP) peptide of procollagen type III, matrix metalloproteinases (MMP-1, MMP-2, and MMP-9), and tissue inhibitor of MMP levels were assayed. Using receiver operating characteristic curve analysis, MMP-2 (AUC=0.91; 95% CI: 0.84, 0.98), CITP (0.83; 0.72, 0.92), PICP (0.82; 0.72, 0.92), B-type natriuretic peptide (BNP) (0.82; 0.73, 0.91), MMP-9 (0.79; 0.68, 0.89), and PIIINP (0.78; 0.66, 0.89) levels were significant predictors of HF-PEF (P<0.01 for all). Carboxytelo peptides of procollagen type I (AUC=0.74; 95% CI: 0.62, 0.86), MMP-2 (0.73; 0.62, 0.84), PIIINP (0.73; 0.60, 0.85), BNP (0.69; 0.55, 0.83) and PICP (0.66; 0.54, 0.78) levels were significant predictors of DD (P<0.05 for all). A cutoff of 1585 ng/mL for MMP-2 provided 91% sensitivity and 76% specificity for predicting HF-PEF and combinations of biomarkers could be used to adjust either sensitivity or specificity.
Markers of collagen turnover identify patients with HF-PEF and DD. Matrix metalloproteinase 2 may be more useful than BNP in the identification of HF-PEF. This suggests that these new biochemical tools may assist in identifying patients with these diagnostically challenging conditions.
European Journal of Heart Failure 02/2009; 11(2):191-7. · 4.90 Impact Factor
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ABSTRACT: Disease-modifying drug treatment in heart failure (HF) reduces blood pressure. Titration of these agents is guided by clinic blood pressure readings; however, the impact of such treatment on blood pressure is unknown because diurnal blood pressure patterns remain poorly described. The aim of this study was to examine the impact of additional neurohumoral modulating agents on ambulatory blood pressure monitoring (ABPM) control in patients with systolic HF and examine the relationship between the burden of hypotension and clinical outcomes.
In a prospective analysis on 45 patients undergoing initiation and optimization of additional medications (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or beta-blockers), mean daytime systolic (P = .035) and mean daytime and nocturnal diastolic hypotensive episodes (both P < .001) increased significantly posttitration. There was no change in clinic blood pressure before and after titration. In a cross-sectional analysis on 144 patients, those with the most diastolic hypotensive episodes had higher rates of HF readmissions (P = .01) and the composite end point of all-cause mortality and all-cause readmissions (P = .03).
Additional neurohumoral modulating agents could produce significant increases in 24-hour hypotension burden despite reassuring clinic blood pressure readings. The burden of diastolic hypotension is independently predictive of HF readmissions and the composite end point of all-cause mortality and emergency readmissions.
Journal of cardiac failure 10/2008; 14(7):555-60. · 3.25 Impact Factor
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ABSTRACT: Chronic heart failure (HF) is associated with a poor Health Related Quality of Life (HRQoL). HRQoL has been shown to be a predictor of HF outcomes however, variability in the study designs make it difficult to apply these findings to a clinical setting. The aim of this study was to establish if HRQoL is a predictor of long-term mortality and morbidity in HF patients followed-up in a disease management program (DMP) and if a HRQoL instrument could be applied to aid in identifying high-risk patients within a clinical context.
This is a retrospective analysis of HF patients attending a DMP with 18+/-9 months follow-up. Clinical and biochemical parameters were recorded on discharge from index HF admission and HRQoL measures were recorded at 2 weeks post index admission.
225 patients were enrolled into the study (mean age=69+/-12 years, male=61%, and 78%=systolic HF). In multivariable analysis, all dimensions of HRQoL (measured by the Minnesota Living with HF Questionnaire) were independent predictors of both mortality and readmissions particularly in patients <80 years. A significant interaction between HRQoL and age (Total((HRQoL))age: p<0.001) indicated that the association of HRQoL with outcomes diminished as age increased.
These data demonstrate that HRQoL is a predictor of outcome in HF patients managed in a DMP. Younger patients (<65 years) with a Total HRQoL score of > or =50 are at high risk of an adverse outcome. In older patients > or =80 years HRQoL is not useful in predicting outcome.
International journal of cardiology 10/2008; 139(1):60-7. · 7.08 Impact Factor
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ABSTRACT: New guidelines for implantable cardiac defibrillators (ICD) and cardiac resynchronisation therapy (CRT) have expanded the potential use for device therapy. The implications of this on a community heart failure (HF) population are unknown.
To assess the need for device therapy and the change in need over time.
We reviewed device need in a community HF population using ESC guidelines. Change in need was assessed by comparing data between an annual visit called TP2 and an earlier visit called TP1. Patients' need and change in need between TP1 and TP2 was determined.
210 patients were included; mean age 70+/-12 years, 67% male and 54% ischaemic. At TP1, 34% of patients were suitable for ICD and 3% for CRT. At TP2, 22% and 1% were suitable respectively. Of those suitable for ICD at TP1, 19% lost the need at TP2; in addition 9% of patients unsuitable for ICD at TP1 had acquired the need by TP2. Fifty five percent of patients were unsuitable for ICD at either time point, and 16% were suitable at both time points. CRT need was negligible but also noted to change.
ICD need is substantial in a community HF population, but CRT need is limited. ICD need changes significantly. Identifying those likely to change their need may optimise ICD use.
European Journal of Heart Failure 07/2008; 10(6):601-7. · 4.90 Impact Factor
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ABSTRACT: Heart failure patients have frequent readmissions for acute decompensated heart failure (ADHF).
To examine the feasibility, safety and outcomes of outpatient intravenous (IV) diuretic therapy in treating ADHF.
A retrospective analysis was performed of all patients included in a hospital-based heart failure disease management programme, who received outpatient IV diuretic therapy for the management of ADHF between 2002 and 2006. Changes in clinical and biochemical parameters from time of therapy to stability were measured.
One hundred and seven patients (mean age 71+/-11 years) received outpatient IV diuretic therapy for ADHF IV diuretic administration reduced weight (p<0.001), blood pressure (p<0.01) and BNP (p=0.01). It increased urea (p=0.01) and creatinine (p=0.07). Seventy-two percent of patients stabilised following IV diuretics and did not require admission. No patients were hospitalised for hypotension or hypokalaemia. One patient was hospitalised for renal failure. Two patients died post admission.
Outpatient IV diuretic administration for ADHF is safe, cost effective and reduces hospitalisations. This service may expand the potential of a disease management programme to manage ADHF out of hospital and thereby reduce the hospital dependency of this condition.
European Journal of Heart Failure 03/2008; 10(3):267-72. · 4.90 Impact Factor
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ABSTRACT: Recent advances in pharmacological and pacemaker-based treatments for heart failure (HF) have brought about significant improvements in left ventricular function.
To identify the proportion of treated systolic HF patients in whom left ventricular systolic function improves and/or returns to normal.
This was a retrospective analysis of 221 HF patients. Improvement in left ventricular function was defined as an improvement in ejection fraction (LVEF) of > or =10% on echocardiography. Return to normal was defined as an improvement of LVEF to > or =50% and a reduction in left ventricular end diastolic diameter to < or =55 mm. Changes in BNP were also recorded.
Improvement in LVEF was observed in 44.3% of patients and return to normal systolic function in 10.9%, only 2.3% had both a return to normal echocardiographic parameters and a BNP<100 pg/ml. A higher percentage of the improved group were on target doses of beta-blockers (p=0.004). Baseline BNP was not a predictor of improvement. There was a trend towards a reduction in HF readmissions in the improved group (p=0.07) but no difference in the risk of death or all-cause readmission.
While a substantial proportion of treated HF patients have an improvement in left ventricular function over time, only a small proportion return to normal dimensions and LVEF, underlining the permanent nature of ventricular damage in the vast majority of patients.
European Journal of Heart Failure 12/2007; 9(12):1196-204. · 4.90 Impact Factor
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Journal of cardiac failure 05/2007; 13(3):227-9. · 3.25 Impact Factor
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ABSTRACT: The development of disease management programs has been a major advance in heart failure care, bringing about significant improvements for the heart failure population, with reduction in readmission, better use of guideline therapy and improved survival. However, at present, the majority of such programs focus their attention only on the sicker segment of this population, with little application of this important service to the broader heart failure population, where potentially benefits may be even more impressive. This has led to an imbalance in the care of patients with heart failure, where aspects of management such as regular structured review and education are preferentially given to the group at the later stages of the natural history of the syndrome. This paper argues for a far wider application of the disease management program concept in heart failure care so as to bring the benefits of specialist care, patient education and follow-up to patients at an earlier stage in the natural history of heart failure.
European Journal of Heart Failure 03/2007; 9(2):113-7. · 4.90 Impact Factor
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ABSTRACT: There are conflicting data on the usefulness of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in the optimization of therapy for heart failure (HF). Discordant results may be explained by the intra-individual variability of these peptides. This study evaluates the intraindividual variability of BNP and NT-proBNP and the impact of the covariates of age, sex, and renal function.
Stable HF patients attending our unit were included. Blood samples were drawn 1 hour apart on 2 occasions 1 week apart. Forty-five patients were enrolled (69.6 +/- 12.1 years, 64% male, 84% systolic HF). Within-hour and within-week intraindividual variability were: 6.9% and 21.1% for NT-proBNP; 14.6% and 28.4% for BNP (P < .01 for within-hour comparison of BNP and NT-proBNP). Reference change values over 1 week for NT-proBNP and BNP were 49.2% and 66.2%, respectively. There were no significant relationships identified between variability and age, gender, or glomerular filtration rate.
There is considerable intraindividual variability in these peptides in stable HF patients. Changes of approximately 50% and 66% for NT-proBNP and BNP from week to week are needed to indicate an altered clinical status and caution should be exercised in interpreting serial changes in these peptide levels when monitoring patient responses to treatment or clinical status.
Journal of cardiac failure 03/2007; 13(1):50-5. · 3.25 Impact Factor
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ABSTRACT: To examine the clinical effect of fluid restriction in patients admitted to the hospital with class IV heart failure (HF).
This is a single-blind randomized controlled study. Time to clinical stability was compared between the fluid restricted (FR: n = 34) and free fluid (FF: n = 33) groups respectively showing no significant difference (8.3 +/- 6.3 days versus 7.0 +/- 6.0 days, P = .17). There was no significant difference between groups in time to discontinuation of intravenous diuretic therapy (FR: 2.7 +/- 4.5 days, FF: 3.2 +/- 5.6 days, P = .70). Changes from baseline to achievement of clinical stability in serum urea (P = .23), serum creatinine (P = .14), BNP (P = .42), and sodium (P = .14) did not differ between the FF and FR groups. Baseline serum sodium levels did not predict the time to clinical stability (beta = -0.11, 95% CI: -0.60, 0.23).
Fluid restriction is not an evidence-based therapy although it is occasionally applied in the management of HF. These results suggest that FR is not of any clinical benefit in patients with acute decompensated HF and this hypothesis should be tested in a larger randomized controlled study.
Journal of cardiac failure 03/2007; 13(2):128-32. · 3.25 Impact Factor
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Piotr Ponikowski,
Stefan D Anker,
Joanna Szachniewicz,
Darlington Okonko, Mark Ledwidge,
Robert Zymlinski,
Enda Ryan,
Scott M Wasserman,
Nigel Baker,
Dylan Rosser,
Stuart D Rosen,
Philip A Poole-Wilson,
Waldemar Banasiak,
Andrew J S Coats,
Ken McDonald
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ABSTRACT: This study sought to investigate whether darbepoetin alfa, an erythropoiesis-stimulating protein (ESP), improves exercise capacity in patients with symptomatic chronic heart failure (CHF) and anemia.
Anemia is common in patients with CHF.
In a multicenter, randomized, double-blind, placebo-controlled study, CHF patients with anemia (hemoglobin > or =9.0 to < or =12.0 g/dl) received subcutaneous placebo (n = 22) or darbepoetin alfa (n = 19) at a starting dose of 0.75 microg/kg every 2 weeks for 26 weeks. The primary end point was change in exercise tolerance from baseline to week 27 as measured by peak oxygen uptake (ml/min/kg body weight). Other end points included changes in absolute peak VO2 (ml/min), exercise duration, and health-related quality of life.
Differences (95% confidence interval) in mean changes from baseline to week 27 between treatment groups were 1.5 g/dl (0.5 to 2.4) for hemoglobin concentration (p = 0.005), 0.5 ml/kg/min (-0.7 to 1.7) for peak VO2 (p = 0.40), 45 ml/min (-35 to 127) for absolute peak VO2 (p = 0.27), and 108 s (-11 to 228) for exercise duration (p = 0.075). Patients receiving darbepoetin alfa compared with placebo had an improvement in self-reported Patient's Global Assessment of Change (79% vs. 41%, p = 0.01) but no significant differences in the Kansas City Cardiomyopathy and Minnesota Living with Heart Failure Questionnaire scores. Darbepoetin alfa was well tolerated.
In patients with symptomatic CHF and anemia, darbepoetin alfa increased and maintained hemoglobin concentrations and improved health-related quality of life. A trend toward increased exercise time but not peak VO2 was observed. (Impact of Darbepoetin Alfa on Exercise Tolerance and Left Ventricular Structure in Subjects With Symptomatic Congestive Heart Failure (CHF) and Anemia; http://clinicaltrials.gov/ct/show/NCT00117234?order = 1; NCT00117234).
Journal of the American College of Cardiology 02/2007; 49(7):753-62. · 14.16 Impact Factor
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ABSTRACT: The pathophysiology of diastolic heart failure (DHF) is poorly understood. One potential explanation is an active fibrotic process that produces increased ventricular stiffness, which compromises filling. The present study investigates collagen metabolism in hypertensive patients in different phases of diastolic function with and without proven DHF.
We studied 86 hypertensive patients divided into groups according to the presence of DHF (32 with, 54 without) and phase of diastolic function (20 with normal function, 38 with impaired relaxation, 10 with pseudonormalization, and 16 with restrictive-like filling). Serum carboxy-terminal, amino-terminal, and carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, matrix metalloproteinases (MMPs; total MMP-1, active MMP-2, and MMP-9), and tissue inhibitor of MMPs levels were assayed by radioimmunoassay and ELISA. Doppler-echocardiographic assessment of diastolic filling was made with measurements of E/A ratio, E-wave deceleration time, and isovolumic relaxation time. Serum carboxy-terminal telopeptide of procollagen type I, carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, MMP-2, and MMP-9 levels (P<0.001 for all, controlled for age and gender) were greater in patients with DHF than in those without. When we controlled for age and gender, levels of serum carboxy-terminal telopeptide of procollagen type I, tissue inhibitor of MMP-1, amino-terminal propeptide of procollagen type III (all P<0.001), carboxy-terminal telopeptide of procollagen type I (P=0.008), and MMP-2 (P=0.03) were greater in more severe phases of diastolic dysfunction. Within phases of diastolic dysfunction, serum carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, MMP-2, and MMP-9 were elevated in those with DHF compared with those without DHF (all P<0.001).
These data demonstrate serological evidence of an active fibrotic process in DHF, which is more marked in more severe diastolic dysfunction. This observation may help explain the pathophysiology of DHF and may suggest new avenues for diagnostic and therapeutic intervention.
Circulation 02/2007; 115(7):888-95. · 14.74 Impact Factor
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ABSTRACT: To assess the natural history of left ventricular (LV) structure and function in sequential heart failure admissions with preserved systolic function.
Heart failure (HF) with preserved LV systolic function accounts for between 20% and 30% of typical HF populations. Few data are available concerning the natural history of structural and functional changes in the LV in this patient population.
We consented sequential admissions from the community with confirmed heart failure to participate in this study. Doppler-echocardiography was used to assess Ejection Fraction (EF), LV structure, regional wall motion and parameters of diastolic function including E:A ratio, E-wave deceleration time (DtE) and isovolumic relaxation time (IVRT). Follow-up echocardiography was carried out at three months (mean 103+/-13 days) from discharge.
Of 210 sequential admissions with primary heart failure 56 had preserved systolic function (LVEF> or =45%). Follow-up data at three months were available in 38 patients (mean age 72 years) with preserved LV systolic function. Of the group, 9 had been admitted within three months of discharge, 5 for recurrent HF. Eight patients (21%) exhibited significant decline in LV systolic function at follow-up, all with LVEF<45%. Three exhibited regional wall-motion abnormalities with the remainder showing dilatation and global reduction in function. None of these eight had presented to hospital for any cause other than routine outpatient department (OPD) visits during the 3 months.
Patients with preserved systolic function HF, a significant number may progress to systolic dysfunction with or without clinical events.
International Journal of Cardiology 01/2006; 106(1):95-102. · 7.08 Impact Factor
