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Showing papers by "John G.F. Cleland published in 2015"


Journal ArticleDOI
TL;DR: Neither structured telephone support nor telemonitoring demonstrated effectiveness in reducing the risk of all-cause mortality or heart failure-related hospitalisations in people with chronic heart failure.
Abstract: BackgroundSpecialised disease management programmes for heart failure aim to improve care, clinical outcomes and/or reduce healthcare utilisation. Since the last version of this review in 2010, several new trials of structured telephone support and non-invasive home telemonitoring have been published which have raised questions about their effectiveness.ObjectivesTo review randomised controlled trials (RCTs) of structured telephone support or non-invasive home telemonitoring compared to standard practice for people with heart failure, in order to quantify the effects of these interventions over and above usual care.Search methodsWe updated the searches of the Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology AsseFssment Database (HTA) on the Cochrane Library; MEDLINE (OVID), EMBASE (OVID), CINAHL (EBSCO), Science Citation Index Expanded (SCI-EXPANDED), Conference Proceedings Citation Index-Science (CPCIS) on Web of Science (Thomson Reuters), AMED, Proquest Theses and Dissertations, IEEE Xplore and TROVE in January 2015. We handsearched bibliographies of relevant studies and systematic reviews and abstract conference proceedings. We applied no language limits.Selection criteriaWe included only peer-reviewed, published RCTs comparing structured telephone support or non-invasive home telemonitoring to usual care of people with chronic heart failure. The intervention or usual care could not include protocol-driven home visits or more intensive than usual (typically four to six weeks) clinic follow-up.Data collection and analysisWe present data as risk ratios (RRs) with 95% confidence intervals (CIs). Primary outcomes included all-cause mortality, all-cause and heart failure-related hospitalisations, which we analysed using a fixed-effect model. Other outcomes included length of stay, health-related quality of life, heart failure knowledge and self care, acceptability and cost; we described and tabulated these. We performed meta-regression to assess homogeneity (the null hypothesis) in each subgroup analysis and to see if the effect of the intervention varied according to some quantitative variable (such as year of publication or median age).Main resultsWe include 41 studies of either structured telephone support or non-invasive home telemonitoring for people with heart failure, of which 17 were new and 24 had been included in the previous Cochrane review. In the current review, 25 studies evaluated structured telephone support (eight new studies, plus one study previously included but classified as telemonitoring; total of 9332 participants), 18 evaluated telemonitoring (nine new studies; total of 3860 participants). Two of the included studies trialled both structured telephone support and telemonitoring compared to usual care, therefore 43 comparisons are evident.Non-invasive telemonitoring reduced all-cause mortality (RR 0.80, 95% CI 0.68 to 0.94; participants = 3740; studies = 17; I-2 = 24%, GRADE: moderate-quality evidence) and heart failure-related hospitalisations (RR 0.71, 95% CI 0.60 to 0.83; participants = 2148; studies = 8; I-2 = 20%, GRADE: moderate-quality evidence). Structured telephone support reduced all-cause mortality (RR 0.87, 95% CI 0.77 to 0.98; participants = 9222; studies = 22; I-2 = 0%, GRADE: moderate-quality evidence) and heart failure-related hospitalisations (RR 0.85, 95% CI 0.77 to 0.93; participants = 7030; studies = 16; I-2 = 27%, GRADE: moderate-quality evidence).Neither structured telephone support nor telemonitoring demonstrated effectiveness in reducing the risk of all-cause hospitalisations (structured telephone support: RR 0.95, 95% CI 0.90 to 1.00; participants = 7216; studies = 16; I-2 = 47%, GRADE: very low-quality evidence; non-invasive telemonitoring: RR 0.95, 95% CI 0.89 to 1.01; participants = 3332; studies = 13; I-2 = 71%, GRADE: very low-quality evidence).Seven structured telephone support studies reported length of stay, with one reporting a significant reduction in length of stay in hospital. Nine telemonitoring studies reported length of stay outcome, with one study reporting a significant reduction in the length of stay with the intervention. One telemonitoring study reported a large difference in the total number of hospitalisations for more than three days, but this was not an analysis of length of stay per hospitalisation. Nine of 11 structured telephone support studies and five of 11 telemonitoring studies reported significant improvements in health-related quality of life. Nine structured telephone support studies and six telemonitoring studies reported costs of the intervention or cost effectiveness. Three structured telephone support studies and one telemonitoring study reported a decrease in costs and two telemonitoring studies reported increases in cost, due both to the cost of the intervention and to increased medicalmanagement. Adherence was rated between 55.1% and 98.5% for those structured telephone support and telemonitoring studies which reported this outcome. Participant acceptance of the intervention was reported in the range of 76% to 97% for studies which evaluated this outcome. Seven of nine studies that measured these outcomes reported significant improvements in heart failure knowledge and self-care behaviours.Authors' conclusionsFor people with heart failure, structured telephone support and non-invasive home telemonitoring reduce the risk of all-cause mortality and heart failure-related hospitalisations; these interventions also demonstrated improvements in health-related quality of life and heart failure knowledge and self-care behaviours. Studies also demonstrated participant satisfaction with the majority of the interventions which assessed this outcome.

178 citations


Journal ArticleDOI
TL;DR: It is concluded that the absence of clear diagnostic clinical criteria was the major barrier to progress in HFpEF, and several treatments have shown promising early results and are now being tested in substantial randomized clinical trials.
Abstract: Many uncertainties surround the syndrome of heart failure with preserved ejection fraction (HFpEF), which was the topic reviewed in an Expert Meeting at the University of Ferrara. This concluded that the absence of clear diagnostic clinical criteria was the major barrier to progress. There was general agreement that symptoms or signs of heart failure, normal LVEF despite an elevated plasma concentration of natriuretic peptides, and signs of abnormal LV relaxation, LV filling, LV hypertrophy, or left atrial enlargement, or diastolic dysfunction supported the diagnosis. However, HFpEF, like all heart failure syndromes, is heterogeneous in aetiology and pathophysiology, rather than being a single disease. HFpEF may account for about half of all patients with heart failure. The classical risk factors for developing HFpEF include age and co-morbidities, notably hypertension, atrial fibrillation, and the metabolic syndrome. When complicated by increasing congestion requiring hospital admission, the prognosis is poor; 30% or more of patients will die within 1 year (nearly two-thirds die from cardiovascular causes). Patients with chronic stable symptoms have a much better prognosis. Despite many clinical trials, there is no solid evidence that any treatment alters the natural history of HFpEF. Several treatments have shown promising early results and are now being tested in substantial randomized clinical trials. Further basic research is required to better characterize the disease and accelerate progress. Our review highlights the many difficulties encountered in performing randomized clinical trials in HFpEF, often due to difficulties in characterizing HFpEF itself.

132 citations


Journal Article
TL;DR: This longitudinal study involved patients with type 2 diabetes without baseline CVD followed prospectively since 1995 by a single clinical service and found a survival advantage was found in overweight but not obese patients.
Abstract: This cohort study investigated the association between body weight and prognosis in patients with type 2 diabetes. The authors found that overweight or obese patients were more likely to be hospita...

124 citations


Journal ArticleDOI
TL;DR: In this paper, the authors investigated the association between body weight and prognosis in a large cohort of patients with type 2 diabetes followed for a prolonged period, and found that being overweight was associated with a lower mortality risk, whereas obese patients (BMI >30 kg/m²) had a mortality risk similar to that of normal-weight persons.
Abstract: Background Whether obesity is associated with a better prognosis in patients with type 2 diabetes mellitus is controversial. Objective To investigate the association between body weight and prognosis in a large cohort of patients with type 2 diabetes followed for a prolonged period. Design Prospective cohort. Setting National Health Service, England. Patients Patients with diabetes. Measurements The relationship between body mass index (BMI) and prognosis in patients with type 2 diabetes without known cardiovascular disease at baseline was investigated. Information on all-cause mortality and cardiovascular morbidity (such as the acute coronary syndrome, cerebrovascular accidents, and heart failure) was collected. Cox regression survival analysis, corrected for potential modifiers, including cardiovascular risk factors and comorbid conditions (such as cancer, chronic kidney disease, and lung disease), was done. Results 10,568 patients were followed for a median of 10.6 years (interquartile range, 7.8 to 13.4). Median age was 63 years (interquartile range, 55 to 71), and 54% of patients were men. Overweight or obese patients (BMI >25 kg/m²) had a higher rate of cardiac events (such as the acute coronary syndrome and heart failure) than those of normal weight (BMI, 18.5 to 24.9 kg/m²). However, being overweight (BMI, 25 to 29.9 kg/m²) was associated with a lower mortality risk, whereas obese patients (BMI >30 kg/m²) had a mortality risk similar to that of normal-weight persons. Patients with low body weight had the worst prognosis. Limitation Data about cause of death were not available. Conclusion In this cohort, patients with type 2 diabetes who were overweight or obese were more likely to be hospitalized for cardiovascular reasons. Being overweight was associated with a lower mortality risk, but being obese was not. Primary funding source National Institute for Health Research and University of Hull.

117 citations


Journal ArticleDOI
TL;DR: In patients with HF, LAEF predicts adverse outcome independently of other measures of cardiac dysfunction, and increasing age and decreasing LAEF predicted incident AF.
Abstract: Background Left atrial (LA) volume is an important marker of cardiac dysfunction and cardiovascular outcome in heart failure (HF), but LA function is rarely measured. Methods Left atrial emptying function (LAEF), its clinical associations and prognostic value was studied in outpatients referred with suspected HF who were in sinus rhythm and had cardiac magnetic resonance imaging (CMRI). Heart failure was defined as relevant symptoms and signs with either a left ventricular ejection fraction (LVEF) 400 pg/mL (or >125 pg/mL if taking loop diuretics). Results Of 982 patients, 664 fulfilled the HF criteria and were in sinus rhythm. The median (interquartile range, IQR) LAEF was 42 (31–51)% and 55 (48–61)% in patients with and without HF ( P < 0.001). Patients with HF in the lowest quartile of LAEF (23%; IQR: 17–28%) had lower LV and right ventricular (RV) EF, and greater LV and RV mass and higher plasma NTproBNP than those in the highest quartile of LAEF (56%; IQR: 53–61%). Log[LAEF] and log[NTproBNP] were inversely correlated ( r = −0.410, P < 0.001). During a median follow-up of 883 (IQR: 469–1626) days, 394 (59%) patients with HF died or were admitted with HF and 101 (15%) developed atrial fibrillation (AF). In a multivariable Cox model, increasing LAEF, but not LVEF, was independently associated with survival (HR for 10% change: 0.81 (95%CI: 0.73–0.90), P = <0.001). Increasing age and decreasing LAEF predicted incident AF. Conclusions In patients with HF, LAEF predicts adverse outcome independently of other measures of cardiac dysfunction.

109 citations


Journal ArticleDOI
TL;DR: Whether discontinuation of ACEi/ARBs can improve or stabilize renal function in patients with advanced progressive CKD will show whether this simple intervention can improve laboratory and clinical outcomes, including progression to end-stage renal disease, without causing an increase in cardiovascular events.
Abstract: Background Blood pressure (BP) control and reduction of urinary protein excretion using agents that block the renin–angiotensin aldosterone system are the mainstay of therapy for chronic kidney disease (CKD). Research has confirmed the benefits in mild CKD, but data on angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use in advanced CKD are lacking. In the STOP-ACEi trial, we aim to confirm preliminary findings which suggest that withdrawal of ACEi/ARB treatment can stabilize or even improve renal function in patients with advanced progressive CKD.

91 citations


Journal ArticleDOI
TL;DR: Several easily obtained baseline demographic and clinical variables, beyond ejection fraction and New York Heart Association functional class, are independently associated with a disproportionately increased risk of sudden death.

73 citations



Journal ArticleDOI
TL;DR: In this article, the authors explored the efficacy and safety of rivaroxaban 2.5 mg compared with placebo (with standard care) after an exacerbation of established heart failure in patients with reduced ejection fraction (HF-rEF) and documented coronary artery disease.
Abstract: Aims Thrombin is a critical element of crosstalk between pathways contributing to worsening of established heart failure (HF). The aim of this study is to explore the efficacy and safety of rivaroxaban 2.5 mg bid compared with placebo (with standard care) after an exacerbation of HF in patients with reduced ejection fraction (HF-rEF) and documented coronary artery disease. Methods This is an international prospective, multicentre, randomized, double-blind, placebo-controlled, event-driven study of approximately 5000 patients for a targeted 984 events. Patients must have a recent symptomatic exacerbation of HF, increased plasma concentrations of natriuretic peptides (B-type natriuretic peptide ≥200 pg/mL or N-terminal pro–B-type natriuretic peptide ≥800 pg/mL), with left ventricular ejection fraction ≤40% and coronary artery disease. Patients requiring anticoagulation for atrial fibrillation or other conditions will be excluded. After an index event (overnight hospitalization, emergency department or observation unit admission, or unscheduled outpatient parenteral treatment for worsening HF), patients will be randomized 1:1 to rivaroxaban or placebo (with standard of care). The primary efficacy outcome event is a composite of all-cause mortality, myocardial infarction or stroke. The principal safety outcome events are the composite of fatal bleeding or bleeding into a critical space with potential permanent disability, bleeding events requiring hospitalization and major bleeding events according to International Society on Thrombosis and Haemostasis bleeding criteria. Conclusion COMMANDER HF is the first prospective study of a target-specific oral antithrombotic agent in HF. It will provide important information regarding rivaroxaban use following an HF event in an HF-rEF patient population with coronary artery disease.

67 citations


Journal ArticleDOI
TL;DR: This global, prospective, and observational study is designed to characterize patient trajectories longitudinally during and following an index hospitalization for HF.
Abstract: AimsThe clinical characteristics, initial presentation, management, and outcomes of patients hospitalized with new-onset (first diagnosis) heart failure (HF) or decompensation of chronic HF are poorly understood worldwide. REPORT-HF (International REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure) is a global, prospective, and observational study designed to characterize patient trajectories longitudinally during and following an index hospitalization for HF. MethodsData collection for the registry will be conducted at approximate to 300 sites located in approximate to 40 countries. Comprehensive data including demographics, clinical presentation, co-morbidities, treatment patterns, quality of life, in-hospital and post-discharge outcomes, and health utilization and costs will be collected. Enrolment of approximate to 20 000 adult patients hospitalized with new-onset (first diagnosis) HF or decompensation of chronic HF over a 3-year period is planned with subsequent 3 years follow-up. PerspectiveThe REPORT-HF registry will explore the clinical characteristics, management, and outcomes of HF worldwide. This global research programme may have implications for the formulation of public health policy and the design and conduct of international clinical trials.

49 citations


Journal ArticleDOI
TL;DR: WHF during the first 5 days of admission for AHF occurred in approximately 10% to 15% of patients and was associated with longer length of stay and higher risk for readmission and death and remained significantly associated with adverse outcomes after adjustment for these changes.
Abstract: Objectives These studies conducted analyses to examine patient characteristics and outcomes associated with worsening heart failure (WHF). Background WHF during an admission for acute heart failure (AHF) represents treatment failure and is a potential therapeutic target for clinical trials of AHF. Methods Individual patient data from the PROTECT (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function) and RELAX-AHF (Relaxin in Acute Heart Failure) phase II and III studies were pooled for analysis. Results Of 3,691 patients, death or WHF through day 5 occurred in 12.4%, ranging from 9.5% to 14.5% among studies. A multivariable model provided modest discrimination between patients who did or did not develop WHF (C-index = 0.68). After multivariable adjustment, WHF was associated with a mean increase in length of stay of 5.2 days (95% confidence interval [CI]: 4.6 to 5.8 days) and increased risks of 60-day HF or renal failure readmission or cardiovascular death (hazard ratio [HR]: 1.64, 95% CI: 1.34 to 2.01) and 180-day mortality (HR: 1.93, 95% CI: 1.55 to 2.41) (all p Conclusions WHF during the first 5 days of admission for AHF occurred in approximately 10% to 15% of patients and was associated with longer length of stay and higher risk for readmission and death.

Journal ArticleDOI
TL;DR: The PROTECT trial as mentioned in this paper investigated 2033 patients (median age 72 years) with acute heart failure randomized to rolofylline or placebo, and patients were divided into five groups based on the quintiles of age: ≤59, 60-68, 69-74, 75-79, and ≥80 years.
Abstract: Aims Previous heart failure (HF) trials suggested that age influences patient characteristics and outcome; however, under-representation of elderly patients has limited characterization of this cohort. Whether standard prognostic variables have differential utility in various age groups is unclear. Methods and results The PROTECT trial investigated 2033 patients (median age 72 years) with acute HF randomized to rolofylline or placebo. Patients were divided into five groups based on the quintiles of age: ≤59, 60–68, 69–74, 75–79, and ≥80 years. Baseline characteristics, medications, and outcomes (30-day death or cardiovascular/renal hospitalization, and death at 30 and 180 days) were explored. The prognostic utility of baseline characteristics for outcomes was investigated in the different groups and in those aged <80 years vs. ≥80 years. With increasing age, patients were more likely to be women with hypertension, AF, and higher EF. Increased age was associated with increased risk of 30- and 180-day outcomes, which persisted after multivariable adjustment (hazard ratio for 180-day death = 1.17; 95% confidence interval 1.11–1.24 for each 5-year increase). The prognostic utility of baseline characteristics such as previous HF hospitalization and serum sodium, systolic blood pressure, and NYHA class was attenuated in the elderly for the endpoint of 180-day mortality. An increase in albumin was associated with a greater reduction in risk in patients aged ≥80 years vs. <80 years. Conclusions In a large trial of acute HF, there were differences in baseline characteristics and outcomes amongst patients of different ages. Standard prognostic variables exhibit different utility in elderly patients.


Journal ArticleDOI
15 Jul 2015-Heart
TL;DR: Ultrasound assessment of the internal jugular vein identifies outpatients with HF who have a higher risk of an adverse outcome and only increasing NT-proBNP and ultrasound assessment of internaljugular vein were independently associated with prognosis.
Abstract: Aims Jugular venous distension is a classical sign of heart failure (HF) but it can be difficult to assess clinically. Methods and results Outpatients with HF and control subjects were assessed. Internal jugular vein diameter (JVD) was measured using a linear high-frequency ultrasound probe (10 MHz) at rest, after a Valsalva manoeuvre and during deep inspiration. JVD ratio was calculated as the maximum diameter during Valsalva to that measured at rest. 311 patients (mean age 71 years, mean left ventricular EF 42%, median (IQR) amino-terminal pro-brain natriuretic peptide 979 (441–2007) ng/L) and 66 controls were included. JVD (median and IQR range) at rest was smaller in controls (0.16 (0.14–0.20) cm) than in patients with HF (0.23 (0.17–0.33) cm; p Conclusions Ultrasound assessment of the internal jugular vein identifies outpatients with HF who have a higher risk of an adverse outcome. Clinical trial registration NCT01872299.

Journal ArticleDOI
TL;DR: It is suggested that the benefits of β-blockers are neutralized in patients with atrial fibrillation due to the induction of pauses that may impair cardiac function leading to worsening heart failure or cause arrhythmias resulting in death.

Journal ArticleDOI
TL;DR: To investigate the prognostic significance of hospitalization for worsening heart failure (WHF), myocardial infarction (MI), and stroke in patients with chronic heart failure, a large number of patients are admitted to hospital for treatment of these conditions.
Abstract: Aims To investigate the prognostic significance of hospitalization for worsening heart failure (WHF), myocardial infarction (MI), and stroke in patients with chronic heart failure (HF). Methods and results We studied 5011 patients with HF and reduced EF (HF-REF) in the CORONA trial and 4128 patients with HF and preserved EF (HF-PEF) in the I-Preserve trial. Adjusted hazard ratios (HRs) for death were estimated for 0–30 days and ≥31 days after first post-randomization WHF, MI, or stroke used as a time-dependent variable, compared with patients with none of these events. In CORONA, 1616 patients (32%) had post-randomization first events (1223 WHF, 216 MI, 177 stroke), and the adjusted HR for mortality ≤30 days after an event was: WHF 7.21 [95% confidence interval (CI) 2.05–25.40], MI 23.08 (95% CI 6.44–82.71), and stroke 32.15 (95% CI 8.93–115.83). The HR for mortality at >30 days was: WHF 3.62 (95% CI 3.11–4.21), MI 4.41 (95% CI 3.23–6.02), and stroke 3.19 (95% CI 2.21–4.61). In I-Preserve, 896 patients (22%) experienced a post-randomization event (638 WHF, 111 MI, 147 stroke). The HR for mortality ≤30 days was WHF 31.77 (95% CI 7.60–132.81), MI 154.77 (95% CI 34.21–700.17), and stroke 223.30 (95% CI 51.42–969.78); for >30 days it was WHF 3.36 (95% CI 2.79–4.05), MI 3.29 (95% CI 2.14–5.06), and stroke 5.13 (95% CI 3.61–7.29). Conclusions In patients with both HF-REF and HF-PEF, hospitalization for WHF was associated with high early and late mortality. The early relative risk of death was not as great as following MI or stroke, but the longer term relative risk of death was similar following all three types of event. Numerically, more deaths occurred following WHF because it was a much more common event.

Journal ArticleDOI
TL;DR: Self-reported self-care behavior scores improved significantly during the period of observation, and the objective evidence of adherence to daily weight and blood pressure measurements was high and remained stable over time, but adherence todaily reporting of symptoms was lower and declined in the long-term.
Abstract: Purpose: The purpose of this study was to evaluate a novel online education and coaching program to promote self-care among patients with heart failure. In this program, education and coaching content is automatically tailored to the knowledge and behavior of the patient. Patients and methods: The evaluation of the program took place within the scope of the HeartCycle study. This multi-center, observational study examined the ability of a third generation telehealth system to enhance the management of patients recently (less than60 days) admitted to the hospital for worsening heart failure or outpatients with persistent New York Heart Association (NYHA) Functional Classification III/IV symptoms. Self-reported self-care behavior was assessed at baseline and study-end by means of the 9-item European Heart Failure Self-care Behavior scale. Adherence to daily weighing, blood pressure monitoring, and reporting of symptoms was determined by analyzing the systems database. Results: Of 123 patients enrolled, the mean age was 66 +/- 12 years, 66% were in NYHA III and 79% were men. Self-reported self-care behavior scores (n=101) improved during the study for daily weighing, low-salt diet, physical activity (Pless than0.001), and fluid restriction (Pless than0.05). Average adherence (n=120) to measuring weight was 90%+/- 16%, to measuring blood pressure was 89%+/- 17% and to symptom reporting was 66%+/- 32%. Conclusion: Self-reported self-care behavior scores improved significantly during the period of observation, and the objective evidence of adherence to daily weight and blood pressure measurements was high and remained stable over time. However, adherence to daily reporting of symptoms was lower and declined in the long-term.

Journal ArticleDOI
TL;DR: In this review, the existing home monitoring modalities, relevant trials and focus on future directions for telemonitoring are discussed.
Abstract: Heart failure (HF) is a leading cause of hospitalisations in older people. Several strategies, supported by novel technologies, are now available to monitor patients’ health from a distance. Although studies have suggested that remote monitoring may reduce HF hospitalisations and mortality, the study of different patient populations, the use of different monitoring technologies and the use of different endpoints limit the generalisability of the results of the clinical trials reported, so far. In this review, we discuss the existing home monitoring modalities, relevant trials and focus on future directions for telemonitoring.

Journal ArticleDOI
TL;DR: Almost half of patients with stable CAD have profound bone marrow iron depletion that can be accurately assessed non-invasively using serum soluble transferrin receptor, the diagnostic gold-standard for ID.

Journal ArticleDOI
TL;DR: It is shown that patients with a QRS duration or <130 ms may be harmed by CRT even if they have evidence of left ventricular dyssynchrony on echocardiography and that this applies similarly to those with aQRS duration of <120 ms and those with QRS 120–130 ms.
Abstract: This editorial refers to ‘The effect of QRS duration on cardiac resynchronization therapy in patients with a narrow QRS complex: a subgroup analysis of the EchoCRT Trial’, by J. Steffel et al ., on page doi:10.1093/eurheartj/ehv242. Guidelines give a strong recommendation for cardiac resynchronization therapy (CRT) for selected patients with heart failure.1,2 These recommendations are relatively complex and could be improved and simplified in the light of new data. In this issue of the journal, the EchoCRT investigators show, in a prospective randomized controlled trial, that patients with a QRS duration or <130 ms may be harmed by CRT even if they have evidence of left ventricular dyssynchrony on echocardiography and that this applies similarly to those with a QRS duration of <120 ms and those with QRS 120–130 ms.3 If we knew exactly how CRT worked, then making recommendations on how and in whom it should be used would be easy. However, the precise mechanism(s) by which CRT reduces morbidity and mortality are incompletely understood, which makes targeting the right patients for intervention difficult.4,5 Like many other treatments for heart failure, a single mode of action for CRT seems unlikely and therefore it would be surprising if any single measurement predicted benefit accurately. However, QRS duration certainly helps where many other measures have failed. The mechanisms underlying the effect of CRT probably vary from one patient to the next and, over time, even within an individual patient, because the cardiovascular system is dynamic by design. Potential mechanisms of effect include not only correction of inter- and intraventricular mechanical dyssynchrony, atrioventricular dyssynchrony, and mitral regurgitation, but also long-term effects …

Journal ArticleDOI
01 Jan 2015-Europace
TL;DR: The Cardiac Resynchronization Therapy Survey II is a 6 months snapshot survey initiated by two ESC Associations, the European Heart Rhythm Association and the Heart Failure Association, which is designed to describe clinical practice regarding implantation of CRT devices in a broad sample of hospitals in 47 ESC member countries.
Abstract: The Cardiac Resynchronization Therapy (CRT) Survey II is a 6 months snapshot survey initiated by two ESC Associations, the European Heart Rhythm Association and the Heart Failure Association, which is designed to describe clinical practice regarding implantation of CRT devices in a broad sample of hospitals in 47 ESC member countries. The large volume of clinical and demographic data collected should reflect current patient selection, implantation, and follow-up practice and provide information relevant for assessing healthcare resource utilization in connection with CRT. The findings of this survey should permit representative benchmarking both nationally and internationally across Europe.

Journal ArticleDOI
TL;DR: While high-risk patients may show the greatest short-term gain, the dramatic growth of lifespan-gain over time means that it is the lower risk patients, e.g. primary prevention ICD implantation, who gain the most life-years over their lifetime.
Abstract: Background In at-risk patients with left ventricular dysfunction, implantable cardioverter defibrillators (ICDs) prolong life. Implantable cardioverter defibrillators are increasingly implanted for primary prevention and therefore into lower risk patients. Trial data have demonstrated the benefit of these devices but does not provide an estimate of potential lifespan-gain over longer time periods, e.g. a patient's lifespan. Methods Using data from landmark ICD trials, lifespan-gain was plotted against baseline annual mortality in the individual trials. Lifespan-gain was then extrapolated to a time-horizon of >20 years while adjusting for increasing ‘competing’ risk from ageing and non-sudden cardiac death (pump failure). Results At 3 years, directly observed lifespan-gain was strongly dependent on baseline event rate ( r = 0.94, P 20 years were greatest in lower risk patients (∼5 life-years for 5% baseline mortality, ∼2 life-years for 15% baseline mortality). Increased competing risks significantly reduce lifespan-gain from ICD implantation. Conclusion While high-risk patients may show the greatest short-term gain, the dramatic growth of lifespan-gain over time means that it is the lower risk patients, e.g. primary prevention ICD implantation, who gain the most life-years over their lifetime . Benefit is underestimated when only trial data are assessed as trials can only maintain randomization over limited periods. Lifespan-gain may be further increased through advances in ICD device programming.

Journal ArticleDOI
19 Aug 2015-PLOS ONE
TL;DR: Intermediate serum sFRP3 levels are associated with better survival and fewer CV events than low or high sFRp3 levels, independently of conventional risk factors, in older patients with chronic systolic HF of ischemic origin.
Abstract: Background We have previously demonstrated an association between increased sFRP3 expression and adverse outcome in a population of HF irrespective of cause and left ventricular ejection fraction. In this study we evaluated the prognostic value of sFRP3 in older patients with chronic systolic HF of ischemic origin. Methods We evaluated sFRP3, by tertiles, as a risk factor for the primary endpoint (cardiovascular [CV] mortality, nonfatal myocardial infarction, nonfatal stroke), all-cause mortality, CV mortality, death from worsening HF (WHF), any coronary event, including sudden death, as well as hospitalizations for CV causes and WHF in 1444 patients from the CORONA population, randomly assigned to 10 mg rosuvastatin or placebo. Results Kaplan-Meier curves for the primary endpoint, as well as all-cause- and CV mortality revealed a markedly better survival for patients with sFRP3 levels in the middle tertile of compared to the 1st and 3rd tertile. In multivariable Cox-regression, after full adjustment including high-sensitive CRP and NT-proBNP, a lower event rate for the primary end point, all cause and CV mortality was observed for patients with tertile 2 sFRP3 levels (HR 0.57 [0.44–0.74], 0.55 [0.44–0.74] and 0.52 [0.39–0.69]; p<0.001), as well as for the number of coronary events (HR 0.62 [0.47–0.82], p = 0.001) and sudden death (HR 0.55 [0.37–0.82], p = 0.002). Applying sFRP3 values to the fully adjusted regression model resulted in highly significant continuous net reclassification improvements for the primary endpoint, all cause and CV mortality, coronary events and sudden death (range 0.24–0.31; p≤0.002 for all). Conclusions Intermediate serum sFRP3 levels are associated with better survival and fewer CV events than low or high sFRP3 levels, independently of conventional risk factors, in older patients with chronic systolic HF of ischemic origin. Our study suggests that balanced Wnt activity might confer protective effects in a clinical HF setting. Trial Registration http://www.clinicaltrials.gov NCT00206310

Journal ArticleDOI
TL;DR: In this paper, the authors conducted a post-hoc sub-analysis of a previously published large Cochrane system to evaluate the effectiveness of remote monitoring for older people with heart failure.
Abstract: Background:There are few data regarding the effectiveness of remote monitoring for older people with heart failure. We conducted a post-hoc sub-analysis of a previously published large Cochrane sys...

Journal ArticleDOI
TL;DR: Among patients with HF due to left ventricular systolic dysfunction in sinus rhythm, most are treated with beta-blockers and have a heart rate at rest of <70 beats/min; 12% of these patients might be eligible for ivabradine.
Abstract: Objectives This study sought to characterize patients attending a community heart failure (HF) clinic and identified those who were eligible for optimization of beta-blockers (BB) or ivabradine. Background Among patients with HF due to left ventricular systolic dysfunction in sinus rhythm, those with higher resting heart rate have a worse prognosis. Reducing sinus rate to 50 to 60 beats/min might improve outcomes. Methods A total of 1,000 consecutively scheduled HF clinic follow-up appointments over a 6-month period were reviewed. Demographic, clinical, and echocardiographic data were collected for patients who attended (824 unique patients; 555 men). Mean age was 74 ± 11 years, median N-terminal pro–B-type natriuretic peptide levels were 1,002 ng/l (interquartile range: 367 to 2,151 ng/l), and the mean left ventricular ejection fraction (LVEF) was 44 ± 11%. A total of 202 (25%), 252 (31%), and 370 (45%) patients had LVEFs of ≤35%, 36% to 49%, and ≥50%, respectively. Of patients with LVEF ≤35%, 142 (70%) were in sinus rhythm. Results At 70 clinic visits, 58 patients with LVEFs of ≤35% were in sinus rhythm and had heart rates ≥70 beats/min. Of these, 13 patients had their BB dose increased, 20 were potentially eligible for, but did not have, BB uptitration, 15 were already taking target doses of BBs, and 10 patients were reported to be intolerant of higher doses. Thus, 25 patients were potentially eligible for ivabradine according to European Society of Cardiology guidelines; this number dropped to 14 when the United Kingdom National Institute for Health and Care Excellence guidelines were applied. Conclusions Among patients with LVEFs of ≤35%, most are treated with BBs and have a heart rate at rest of

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TL;DR: There is little evidence to support the use of either drug alone in CHF, but on direct comparison H&N appears inferior to ACEI.

Journal ArticleDOI
TL;DR: Worsening heart failure symptoms despite initial therapy during admission for acute heart failure is associated with worse outcomes and the intensity of WHF therapy with outcomes is unknown.
Abstract: BackgroundWorsening heart failure (WHF) symptoms despite initial therapy during admission for acute heart failure (AHF) is associated with worse outcomes. The association between the time of the WHF event and the intensity of WHF therapy with outcomes is unknown. Methods and resultsIn the PROTECT trial of 2033 AHF patients, we investigated the association between time of occurrence of WHF and intensity of therapy, with subsequent outcomes. WHF was defined by standardized, physician-determined assessment. Early WHF was defined as occurring on days 2-3 and late on days 4-7. Low intensity included restarting/increasing diuretics or vasodilators and high intensity included initiation of inotropes, vasopressors, inodilators, or mechanical support. Outcomes were death or cardiovascular/renal hospitalization over 60days and death over 180days. Of the 1879 patients with complete follow-up after day 7, 12.7% (n=238) experienced WHF: 47.9% early and 52.1% late. Treatment intensity was low in 72.3% and high in 24.8% (2.9% missing). After adjusting for baseline predictors of outcome, WHF was associated with a trend toward increased 60-day death or cardiovascular/renal hospitalization [hazard ratio (HR) 1.26; 95% confidence interval (CI) 0.99-1.60; P=0.063] and increased 180-day death (HR 1.77; 95% CI 1.33-2.34; P ConclusionsInhospital WHF was associated with increased 180-day death. The time of occurrence and intensity of WHF therapy may provide less prognostic information than whether or not WHF occurred.

01 Jan 2015
TL;DR: Evidence at hand indicates that discrimination by age alone may be not be appropriate when inviting participation in a remote monitoring service for heart failure, and older people with heart failure did benefit from structured telephone support and telemonitoring.
Abstract: Background There are few data regarding the effectiveness of remote monitoring for older people with heart failure. We conducted a post-hoc sub-analysis of a previously published large Cochrane systematic review and meta-analysis of relevant randomized controlled trials to determine whether structured telephone support and telemonitoring were effective in this population. Methods A post hoc sub-analysis of a systematic review and meta-analysis that applied the Cochrane methodology was conducted. Meta-analyses of all-cause mortality, all-cause hospitalizations and heart failure-related hospitalizations were performed for studies where the mean or median age of participants was 70 or more years. Results The mean or median age of participants was 70 or more years in eight of the 16 (n=2,659/5,613; 47%) structured telephone support studies and four of the 11 (n=894/2,710; 33%) telemonitoring studies. Structured telephone support (RR 0.80; 95% CI=0.63-1.00) and telemonitoring (RR 0.56; 95% CI=0.41-0.76) interventions reduced mortality. Structured telephone support interventions reduced heart failure-related hospitalizations (RR 0.81; 95% CI=0.67-0.99). Conclusion Despite a systematic bias towards recruitment of individuals younger than the epidemiological average into the randomized controlled trials, older people with heart failure did benefit from structured telephone support and telemonitoring. These post-hoc sub-analysis results were similar to overall effects observed in the main meta-analysis. While further research is required to confirm these observational findings, the evidence at hand indicates that discrimination by age alone may be not be appropriate when inviting participation in a remote monitoring service for heart failure.

Journal ArticleDOI
TL;DR: Recent hospitalization for HF or an elevated level of NT-proBNP identified patients at higher risk for cardiovascular events, and this risk was increased further when both factors were present.
Abstract: Objectives The aim of this study was to investigate N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and recent heart failure (HF) hospitalization as predictors of future events in heart failure – preserved ejection fraction (HF-PEF). Background Recently, doubt has been expressed about the value of a history of HF hospitalization as a predictor of adverse cardiovascular outcomes in patients with HF and HF-PEF. Methods We estimated rates and adjusted hazard ratios (HRs) for the composite endpoint of cardiovascular death or HF hospitalization, according to history of recent HF hospitalization and baseline NT-proBNP level in the I-PRESERVE (Irbesartan in Heart Failure with Preserved systolic function) trial. Results Rates of composite endpoints in patients with (n = 804) and without (n = 1,963) a recent HF hospitalization were 12.78 (95% confidence interval [CI]: 11.47 to 14.24) and 4.49 (95% CI: 4.04 to 4.99) per 100 person-years, respectively (HR: 2.71; 95% CI: 2.33 to 3.16). For patients with NT-proBNP concentrations >360 pg/ml (n = 1,299), the event rate was 11.51 (95% CI: 10.54 to 12.58) compared to 3.04 (95% CI: 2.63 to 3.52) per 100 person-years in those with a lower level of NT-proBNP (n = 1468) (HR: 3.19; 95% CI: 2.68 to 3.80). In patients with no recent HF hospitalization and NT-proBNP ≤360 pg/ml (n = 1,187), the event rate was 2.43 (95% CI: 2.03 to 2.90) compared with 17.79 (95% CI: 15.77 to 20.07) per 100 person-years when both risk predictors were present (n = 523; HR: 6.18; 95% CI: 4.96 to 7.69). Conclusions Recent hospitalization for HF or an elevated level of NT-proBNP identified patients at higher risk for cardiovascular events, and this risk was increased further when both factors were present.

Journal ArticleDOI
TL;DR: This review highlights the importance of a multidisciplinary approach to acute heart failure with particular focus on the chain-of-care delivered by the various services within the healthcare system.
Abstract: Acute heart failure describes the rapid deterioration, over minutes, days or hours, of symptoms and signs of heart failure. Its management is an interdisciplinary challenge that requires the cooperation of various specialists. While emergency providers, (interventional) cardiologists, heart surgeons, and intensive care specialists collaborate in the initial stabilization of acute heart failure patients, the involvement of nurses, discharge managers, and general practitioners in the heart failure team may facilitate the transition from inpatient care to the outpatient setting and improve acute heart failure readmission rates. This review highlights the importance of a multidisciplinary approach to acute heart failure with particular focus on the chain-of-care delivered by the various services within the healthcare system.