Carmel Conlon

Diastolic Heart Failure Evidence of Increased Myocardial Collagen Turnover Linked to Diastolic Dysfunction

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 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). 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.

Natriuretic peptide-based screening and collaborative care for heart failure: the STOP-HF randomized trial.

IMPORTANCE Prevention strategies for heart failure are needed. OBJECTIVE To determine the efficacy of a screening program using brain-type natriuretic peptide (BNP) and collaborative care in an at-risk population in reducing newly diagnosed heart failure and prevalence of significant left ventricular (LV) systolic and/or diastolic dysfunction. DESIGN, SETTING, AND PARTICIPANTS The St Vincents Screening to Prevent Heart Failure Study, a parallel-group randomized trial involving 1374 participants with cardiovascular risk factors (mean age, 64.8 [SD, 10.2] years) recruited from 39 primary care practices in Ireland between January 2005 and December 2009 and followed up until December 2011 (mean follow-up, 4.2 [SD, 1.2] years). INTERVENTION Patients were randomly assigned to receive usual primary care (control condition; n=677) or screening with BNP testing (n=697). Intervention-group participants with BNP levels of 50 pg/mL or higher underwent echocardiography and collaborative care between their primary care physician and specialist cardiovascular service. MAIN OUTCOMES AND MEASURES The primary end point was prevalence of asymptomatic LV dysfunction with or without newly diagnosed heart failure. Secondary end points included emergency hospitalization for arrhythmia, transient ischemic attack, stroke, myocardial infarction, peripheral or pulmonary thrombosis/embolus, or heart failure. RESULTS A total of 263 patients (41.6%) in the intervention group had at least 1 BNP reading of 50 pg/mL or higher. The intervention group underwent more cardiovascular investigations (control, 496 per 1000 patient-years vs intervention, 850 per 1000 patient-years; incidence rate ratio, 1.71; 95% CI, 1.61-1.83; P<.001) and received more renin-angiotensin-aldosterone system-based therapy at follow-up (control, 49.6%; intervention, 56.5%; P=.01). The primary end point of LV dysfunction with or without heart failure was met in 59 (8.7%) of 677 in the control group and 37 (5.3%) of 697 in the intervention group (odds ratio [OR], 0.55; 95% CI, 0.37-0.82; P = .003). Asymptomatic LV dysfunction was found in 45 (6.6%) of 677 control-group patients and 30 (4.3%) of 697 intervention-group patients (OR, 0.57; 95% CI, 0.37-0.88; P = .01). Heart failure occurred in 14 (2.1%) of 677 control-group patients and 7 (1.0%) of 697 intervention-group patients (OR, 0.48; 95% CI, 0.20-1.20; P = .12). The incidence rates of emergency hospitalization for major cardiovascular events were 40.4 per 1000 patient-years in the control group vs 22.3 per 1000 patient-years in the intervention group (incidence rate ratio, 0.60; 95% CI, 0.45-0.81; P = .002). CONCLUSION AND RELEVANCE Among patients at risk of heart failure, BNP-based screening and collaborative care reduced the combined rates of LV systolic dysfunction, diastolic dysfunction, and heart failure. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00921960.

Diagnosis of heart failure with preserved ejection fraction: improved accuracy with the use of markers of collagen turnover

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.

Quality of life predicts outcome in a heart failure disease management program

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Disease management programs for heart failure: not just for the 'sick' heart failure population.

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.

Causes and consequences of nonpersistence with heart failure medication.

Persistence with therapy may be more easily and objectively identified in the clinical setting than compliance and recent work has shown it to be linked to mortality in heart failure (HF). The aim of this study was to determine the extent, causes, and clinical impact of nonpersistence with disease-modifying therapy in a retrospective cohort study of 183 patients with systolic HF participating in a disease management program. The main outcome measurements were reasons/determinants of nonpersistence and its impact on hospitalizations. Fifty-three patients (29%) had 74 separate occurrences of nonpersistence with disease-modifying therapy. There was no medical reason for discontinuing medications in 50% of occurrences, whereas medication was discontinued for an adverse reaction in 30% and for a justified medical reason in 15% of occurrences. Nonpersistence was a significant predictor of all-cause readmission (hazard ratio 3.20, 95% confidence interval 1.74 to 11.37) and cardiovascular readmission (hazard ratio 4.45, 95% confidence interval 1.74 to 11.37). In the adjusted model, there was no significantly increased risk of HF readmission (hazard ratio 2.41, 95% confidence interval 0.88 to 6.62). In conclusion, nonpersistence with HF therapy is common, is often not medically justified, and is associated with an increased risk of hospitalization.

Multiple Neurohumoral Modulating Agents in Systolic Dysfunction Heart Failure: Are We Lowering Blood Pressure Too Much?

BACKGROUND 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. METHODS AND RESULTS 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). CONCLUSIONS 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.

Can we reduce preventable heart failure readmissions in patients enrolled in a Disease Management Programme

BackgroundDisease Management Programmes (DMPs) are successful in reducing hospital readmissions in heart failure (HF). However, there remain a number of patients enrolled in a DMP who are readmitted with HF. The primary aim of the study was to determine the proportion of preventable readmissions (PR). The secondary aim was to recognise patient characteristics which would identify certain patients at risk of having a PR.MethodsA retrospective chart search was performed on patients readmitted over a 1-year period.Results38.5% of readmissions were classified as PR. None of these patients made prior contact with the DMP. Admission levels of BNP, potassium, urea and creatinine were significantly lower in the PR group.ConclusionDMP have proven benefits in reducing hospital readmission nonetheless a significant proportion of these readmissions are preventable. Further work is required to prospectively analyse why these patients fail to contact the DMP.

B-type natriuretic peptide measurement in primary care; magnitude of associations with cardiovascular risk factors and their therapies. Observations from the STOP-HF (St. Vincent's Screening TO Prevent Heart Failure) study.

Abstract Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Progression of left atrial volume index in a population at risk for heart failure: a substudy of the STOP-HF (St Vincent's Screening TO Prevent Heart Failure) trial

Limited data are available concerning the evolution of the left atrial volume index (LAVI) in pre‐heart failure (HF) patients. The aim of this study was to investigate clinical characteristics and serological biomarkers in a cohort with risk factors for HF and evidence of serial atrial dilatation.