Background-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. Methods and Results-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 carboxyterminal 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 (PϽ0.001 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 PϽ0.001), carboxy-terminal telopeptide of procollagen type I(Pϭ0.008), and MMP-2 (Pϭ0.03) 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 PϽ0.001). Conclusions-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.
Background: Weight gain and increase in B-Type Natriuretic Peptide have been advocated as means of aiding diagnosis of heart failure. However, there are few data to support the use of these criteria in diagnosing clinical deterioration in patients with established disease. Aims: This prospective study examines the sensitivity and specificity of absolute and relative changes in BNP and weight in determining the early onset of clinical deterioration in patients with established heart failure. Methods: All patients who presented to the outpatient clinic with completed self-reported daily weight books, baseline BNP measurement, outpatient BNP measurement and assessment by a cardiologist blinded to BNP and weight were included. Each patient was determined as clinically stable (CS) or in clinical deterioration (CD). Receiver operating characteristic (ROC) curves and sensitivity and specificity calculations for various absolute and relative BNP and weight changes were carried out. Results: Weight and BNP changes were examined in 34 CS presentations (mean age 69.5 T 16.1 years) and 43 CD presentations (mean age 70.0 T 10.6 years). ROC analysis demonstrated that neither weight nor BNP changes in absolute or relative values predicted clinical deterioration in this study population adequately (AUC values ranging from 0.64 to 0.66).Conclusions: These data demonstrate that increase in body weight and BNP in isolation are not sensitive in assessing clinical deterioration in established heart failure. These observations may need to be emphasized in patient education and to physicians involved in assessment of heart failure patients.
AimsStudies suggest that patients with advanced heart failure (HF) have unmet palliative care (PC) needs. However, many of these studies have been retrospective or based on patients receiving poorly coordinated ad hoc care. We aimed to demonstrate whether the PC needs of patients with advanced HF receiving specialist multidisciplinary coordinated care are similar to cancer patients deemed to have specialist PC needs; thereby justifying the extension of specialist PC services to HF patients. Methods and resultsThis was a cross-sectional comparative cohort study of 50 HF patients and 50 cancer patients, using quantitative and qualitative methods. Both patient cohorts were statistically indistinguishable in terms of symptom burden, emotional wellbeing, and quality-of-life scores. HF patients had good access to community and social support. HF patients particularly valued the close supervision, medication monitoring, ease of access to service, telephone support, and key worker provided at the HF unit. A small subset of patients had unmet PC needs. A palliative transition point is described. ConclusionHF patients should not be excluded from specialist PC services. However, the majority of their needs can be met at a HF unit. Recognition of the palliative transition point may be key to ensuring that end-of-life issues are addressed. The palliative transition point needs further evaluation.--
AimsHeart 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. Methods and resultsWe included 85 Caucasian treated hypertensive patients (DD n ¼ 65; both DD and HF-PEF n ¼ 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. 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. ConclusionMarkers 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. ------------------------ KeywordsDiastolic dysfunction † Heart failure with preserved ejection fraction † Markers of collagen turnover † B-type natriuretic peptide
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