Showing papers in "European Journal of Heart Failure in 2009"

Palliative care in heart failure: a position statement from the palliative care workshop of the Heart Failure Association of the European Society of Cardiology

Abstract: Heart failure is a serious condition and equivalent to malignant disease in terms of symptom burden and mortality. At this moment only a comparatively small number of heart failure patients receive specialist palliative care. Heart failure patients may have generic palliative care needs, such as refractory multifaceted symptoms, communication and decision making issues and the requirement for family support. The Advanced Heart Failure Study Group of the Heart Failure Association of the European Society of Cardiology organized a workshop to address the issue of palliative care in heart failure to increase awareness of the need for palliative care. Additional objectives included improving the accessibility and quality of palliative care for heart failure patients and promoting the development of heart failure-orientated palliative care services across Europe. This document represents a synthesis of the presentations and discussion during the workshop and describes recommendations in the area of delivery of quality care to patients and families, education, treatment coordination, research and policy.

Galectin-3: a novel mediator of heart failure development and progression.

Abstract: Galectins are a family of soluble beta-galactoside-binding lectins that play many important regulatory roles in inflammation, immunity, and cancer. Recently, a role for galectin-3 in the pathophysiology of heart failure (HF) has been suggested. Numerous studies have demonstrated the up-regulation of galectin-3 in hypertrophied hearts, its stimulatory effect on macrophage migration, fibroblast proliferation, and the development of fibrosis. The latter observation is particularly relevant as cardiac remodelling is an important determinant of the clinical outcome of HF and is linked to disease progression and poor prognosis. Because galectin-3 expression is maximal at peak fibrosis and virtually absent after recovery, routine measurement in patients with HF may prove valuable to identify those patients at highest risk for readmission or death, thus enabling physicians to tailor the level of care to individual patient needs. This review summarizes the most recent advances in galectin-3 research, with an emphasis on the role galectin-3 plays in the development and progression of HF.

Heart failure and chronic obstructive pulmonary disease: diagnostic pitfalls and epidemiology

Abstract: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are global epidemics incurring significant morbidity and mortality. The combination presents many diagnostic challenges. Clinical symptoms and signs frequently overlap. Evaluation of cardiac and pulmonary function is often problematic and occasionally misleading. Echocardiography and pulmonary function tests should be performed in every patient. Careful interpretation is required to avoid misdiagnosis and inappropriate treatment. Airflow obstruction, in particular, must be demonstrated when clinically euvolaemic. Very high and very low concentrations of natriuretic peptides have high positive and negative predictive values for diagnosing HF in those with both conditions. Intermediate values are less informative. Both conditions are systemic disorders with overlapping pathophysiological processes. In patients with HF, COPD is consistently an independent predictor of death and hospitalization. However, the impact on ischaemic and arrhythmic events is unknown. Greater collaboration is required between cardiologists and pulmonologists to better identify and manage concurrent HF and COPD. The resulting symptomatic and prognostic benefits outweigh those attainable by treating either condition alone.

Liver function abnormalities and outcome in patients with chronic heart failure: data from the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program

Abstract: Aims The prevalence and importance of liver function test (LFT) abnormalities in a large contemporary cohort of heart failure patients have not been systematically evaluated. Methods and results We characterized the LFTs of 2679 patients with symptomatic chronic heart failure from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity program (CHARM). We used multivariable modelling to assess the relationships between baseline LFT values and long-term outcomes. Liver function test abnormalities were common in patients with chronic heart failure, ranging from alanine aminotransferase elevation in 3.1% of patients to low albumin in 18.3% of patients; total bilirubin was elevated in 13.0% of patients. In multivariable analysis, elevated total bilirubin was the strongest LFT predictor of adverse outcome for both the composite outcome of cardiovascular death or heart failure hospitalization (HR 1.21 per 1 SD increase, P < 0.0001) and all-cause mortality (HR 1.19 per 1 SD increase, P < 0.0001). Even after adjustment for other variables, elevated total bilirubin was one of the strongest independent predictors of poor prognosis (by global chi-square). Conclusion Bilirubin is independently associated with morbidity and mortality. Changes in total bilirubin may offer insight into the underlying pathophysiology of chronic heart failure.

A meta-analysis of the prognostic significance of atrial fibrillation in chronic heart failure

Abstract: AIMS: Atrial fibrillation (AF) is one of the commonest sustained arrhythmias in chronic heart failure (CHF), although the prognostic implications of the presence of AF in CHF remain controversial. We have therefore performed this meta-analysis to study the effects of the presence of AF on mortality in CHF patients. METHODS AND RESULTS: A systematic MEDLINE search for all randomized trials and observational studies in which the influence of AF on CHF mortality was investigated and meta-analysis of the mortality data was performed. A total of 16 studies were identified of which 7 were randomized trials and 9 were observational studies including 30,248 and 23,721 patients, respectively. An adjusted meta-analysis of the data revealed that the presence of AF is associated with an adverse effect on total mortality with an odds ratio (OR) of 1.40 [95% confidence interval (CI) 1.32-1.48, P < 0.0001] in randomized trials and an OR of 1.14 (95% CI 1.03-1.26, P < 0.05) in observational studies. This increase in mortality associated with the presence of AF was observed in subgroups of CHF patients with both preserved and impaired left ventricular (LV) systolic function. CONCLUSION: In conclusion, meta-analysis of 16 studies involving 53,969 patients suggests that the presence of AF is associated with an adverse prognosis in CHF irrespective of LV systolic function.

Inflammation as a therapeutic target in heart failure? A scientific statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology

Abstract: The increasing prevalence of heart failure poses enormous challenges for health care systems worldwide. Despite effective medical interventions that target neurohumoral activation, mortality and morbidity remain substantial. Evidence for inflammatory activation as an important pathway in disease progression in chronic heart failure has emerged in the last two decades. However, clinical trials of ‘anti-inflammatory’ therapies (such as anti-tumor necrosis factor-α approaches) have to date failed to show benefit in heart failure patients. The Heart Failure Association of the European Society of Cardiology recently organized an expert workshop to address the issue of inflammation in heart failure from a basic science, translational and clinical perspective, and to assess whether specific inflammatory pathways may yet serve as novel therapeutic targets for this condition. This consensus document represents the outcome of the workshop and defines key research questions that still need to be addressed as well as considering the requirements for future clinical trials in this area.

The European Heart Failure Self-care Behaviour scale revised into a nine-item scale (EHFScB-9): a reliable and valid international instrument.

Abstract: Aims Improved self-care is the goat of many heart failure (HF) management programmes. The 12-item European Heart Failure Self-Care Behaviour Scale (EHFScB scale) was developed and tested to measure ...

Sleep-disordered breathing in heart failure with normal left ventricular ejection fraction.

Abstract: Aims In patients with systolic heart failure (SHF) a high prevalence of sleep-disordered breathing (SDB) has been documented. The purpose of this study was to investigate the prevalence and type of SDB in patients with heart failure with normal left ventricular ejection fraction (HFNEF). Methods and results Two hundred and forty-four consecutive patients (87 women, aged 65.3 ± 1.4 years) with HFNEF underwent capillary blood gas analysis, measurement of NT-proBNP concentrations, echocardiography, cardiopulmonary exercise testing (CPX), cardiorespiratory polygraphy, and simultaneous right and left heart catheterization. Sleep-disordered breathing was defined as an apnoea–hypopnoea-index (AHI) ≥5/h. Sleep-disordered breathing was documented in 69.3% of all patients, 97 patients (39.8%) presented with OSA and 72 patients (29.5%) with CSA. With an increasing impairment of diastolic function the proportion of SDB, and CSA in particular, increased. Patients with SDB performed worse on CPX and six-minute walk test. Partial pressure of CO2 was lower in CSA, whereas AHI, left atrial diameter, NT-proBNP, LVEDP, PAP, and PCWP were higher. Conclusion There is a high prevalence of SDB in HFNEF. In parallel to SHF, CSA patients in particular are characterized by a more impaired cardiopulmonary function. Whether SDB is of prognostic relevance in HFNEF needs to be determined.

Red blood cell distribution width predicts long‐term outcome regardless of anaemia status in acute heart failure patients

Abstract: Aims To study the long-term prognostic value of red blood cell distribution width (RDW) in patients hospitalized with acute heart failure (AHF) and to compare the value of this measurement with haemoglobin levels and anaemia status. Methods and results During a 2-year period, we studied 628 consecutive patients (aged 71 years [interquartile range, IQR: 61–77], 68% male) hospitalized with AHF. Demographic, clinical, echocardiographic, and laboratory characteristics were registered at discharge and patients were closely followed-up for 38.1 months [16.5–49.1]. Median RDW was 14.4% [13.5–15.5] and was higher among decedents (15.0% [13.8–16.1] vs. 14.2 [13.3–15.3], P < 0.001). After adjustment for other prognostic factors in a multivariable Cox proportional-hazards model, RDW remained a significant predictor (P = 0.004, HR 1.072, 95% CI 1.023–1.124); whereas, haemoglobin or anaemia status did not add prognostic information. RDW levels above the median were associated with a significantly lower survival rate on long-term follow-up (log rank <0.001). These levels were predictive of death in anaemic patients (n = 263, P = 0.029) and especially in non-anaemic patients (n = 365) (P < 0.001, HR 1.287, 95% CI 1.147–1.445), even after adjustment in the multivariable model. Conclusion Higher RDW levels at discharge were associated with a worse long-term outcome, regardless of haemoglobin levels and anaemia status.

Surface electrocardiogram to predict outcome in candidates for cardiac resynchronization therapy: a sub-analysis of the CARE-HF trial.

Abstract: Aims In CARE-HF, cardiac resynchronization therapy (CRT) lowered morbidity and mortality in patients with moderate to severe heart failure. We examined whether baseline and follow-up electrocardiographic characteristics might predict long-term outcome. Methods and results CARE-HF randomly assigned 409 patients to medical therapy (MT) plus CRT, and 404 patients to MT alone. Electrocardiographic measurements were made at baseline during sinus rhythm, and at 3 months during paced or spontaneous rhythm depending on treatment assignment. Favourable outcome was defined as freedom from death, urgent transplantation, or cardiovascular hospitalization. Among patients assigned to CRT, 39% had unfavourable outcomes including 55 deaths. By single variable analysis, (i) prolonged PR interval, left QRS axis (but not QRS duration), and left bundle branch block (BBB) at baseline, and (ii) heart rate, PR, and QRS duration at 3 months predicted unfavourable outcome. By multiple variable analysis, treatment assignment (P = 0.0001), PR (P = 0.0004), and right BBB (P < 0.00013) at baseline predicted outcome, whereas baseline JTc and QRS duration at 3 months predicted all-cause mortality and heart failure hospitalization (P = 0.0071). Conclusion In CARE-HF, QRS duration at baseline did not predict outcome, but QRS at 3 months was a predictor by single variable analysis. Patients with prolonged PR interval and the 5% of patients with right BBB had a particularly high event rate.

Influence of gender of physicians and patients on guideline-recommended treatment of chronic heart failure in a cross-sectional study.

Abstract: Aims Clinical outcomes of patients with chronic heart failure (CHF) have improved, but evidence-based treatment appears to be imbalanced depending on patients' and physicians' gender. We aimed to determine the interactions of gender with medical treatment of CHF. Methods and results Consecutive patients with CHF (n = 1857) were evaluated regarding co-morbidities, New York Heart Association classification, current medical treatment, and dosage of angiotensin-converting enzyme-inhibitors (ACE-Is) and beta-blockers. Gender of patients and treating physicians was recorded. Baseline characteristics of patients and physicians were comparable for males and females. Female patients were less frequently treated with ACE-Is, angiotensin-receptor blockers, or beta-blockers. Achieved doses were lower in female compared with male patients. Guideline-recommended drug use and achieved target doses tended to be higher in patients treated by female physicians. There was no different treatment for male or female patients by female physicians, whereas male physicians used significantly less medication and lower doses in female patients. In multivariable analysis, female gender of physicians was an independent predictor of use of beta-blockers. Conclusion Treatment of CHF is influenced by patients', but also physicians' gender with regard to evidenced-based drugs and their dosage. Physicians should be aware of this problem in order to avoid gender-related treatment imbalances.

Long-term left ventricular reverse remodelling with cardiac resynchronization therapy: results from the CARE-HF trial

Abstract: Aims The aim of the present study was to assess the long-term effects of cardiac resynchronization therapy (CRT) on the reverse remodelling of the left ventricle (LV). Methods and results The effects of CRT compared with controls on LV dimensions and function were assessed at 3, 9, and 18 months and at the end of study (average 29 months) in 735 (90%) patients with adequate echocardiographic examinations, randomized in the CARE-HF trial. Echocardiographic recordings were submitted to a core laboratory to ensure consistent quantitative analysis. LV volume decreased and ejection fraction increased substantially in the CRT group by 3 months and improved further at each assessment when compared with the control group. Effects were less marked in patients with ischaemic heart disease and those with right ventricular dysfunction, but not in patients with a restrictive LV filling pattern. The extent of reverse remodelling at 18 months showed a modest relationship with baseline interventricular mechanical delay (IVMD). Conclusion CRT induces sustained LV reverse remodelling with the most marked effects occurring within the first 3–9 months. The extent of remodelling in response to CRT is related to the aetiology of heart failure and, to a lesser extent, to the IVMD.

Both in‐ and out‐hospital worsening of renal function predict outcome in patients with heart failure: results from the Coordinating Study Evaluating Outcome of Advising and Counseling in Heart Failure (COACH)

Abstract: The effect of worsening renal function (WRF) after discharge on outcome in patients with heart failure is unknown. We assessed estimated glomerular filtration rate (eGFR) and serum creatinine at admission, discharge, and 6 and 12 months after discharge, in 1023 heart failure patients. Worsening renal function was defined as an increase in serum creatinine of > 26.5 mu mol/L and > 25%. The primary endpoint was a composite of all-cause mortality and heart failure admissions. The mean age of patients was 71 +/- 11 years, and 62% was male. Mean eGFR at admission was 55 +/- 21 mL/min/1.73 m(2). In-hospital WRF occurred in 11% of patients, while 16 and 9% experienced WRF from 0 to 6, and 6 to 12 months after discharge, respectively. In multivariate landmark analysis, WRF at any point in time was associated with a higher incidence of the primary endpoint: hazard ratio (HR) 1.63 (1.10-2.40), P = 0.014 for in-hospital WRF, HR 2.06 (1.13-3.74), P = 0.018 for WRF between 0-6 months, and HR 5.03 (2.13-11.88), P <0.001 for WRF between 6-12 months. Both in- and out-hospital worsening of renal function are independently related to poor prognosis in patients with heart failure, suggesting that renal function in heart failure patients should be monitored long after discharge.

Red cell distribution width: an inexpensive and powerful prognostic marker in heart failure.

Abstract: Aims Red cell distribution width (RDW) is prognostic in patients with heart failure (HF), but it has not been compared with N-terminal brain natriuretic peptide (NT-proBNP). We sought to make this comparison. Methods and results Patients referred to a specialist HF clinic between 2001 and 2008 were assessed comprehensively including medical history, echocardiogram, and blood tests. Cox-regression was used to assess the multivariable relationship between RDW, NT-proBNP, and all-cause mortality. A total of 1087 patients were recruited; median (IQR) follow-up was 52 months (29–66); age 72 years (64–78); 74% male; 70% ischaemic heart disease; 20% diabetic; 85% NYHA ≥ 2, and 63% with at least moderate LV impairment (EF < 35% equivalent). In a multivariable model, both RDW and NT-proBNP were independently prognostic (RDW: χ2 = 21.8 vs. 49.1 both P < 0.001). In a model using quartiles of each variable, the relative risk for each was similar for the second and third quartiles compared with the first. A larger increase in risk for NT-proBNP is seen in the fourth quartile. Conclusion Red cell distribution width is a readily available test in the HF-population with similar independent prognostic power to NT-proBNP across the first to third quartiles. Prognostic models in HF should include RDW and further investigation is necessary to determine the pathological mechanism of the relationship.

Levosimendan vs. dobutamine: outcomes for acute heart failure patients on β-blockers in SURVIVE

Abstract: Aims Many chronic heart failure (CHF) patients take β-blockers. When such patients are hospitalized for decompensation, it remains unclear how ongoing β-blocker treatment will affect outcomes of acute inotrope therapy. We aimed to assess outcomes of SURVIVE patients who were on β-blocker therapy before receiving a single intravenous infusion of levosimendan or dobutamine. Methods and results Cox proportional hazard regression revealed all-cause mortality benefits of levosimendan treatment over dobutamine when the SURVIVE population was stratified according to baseline presence/absence of CHF history and use/non-use of β-blocker treatment at baseline. All-cause mortality was lower in the CHF/levosimendan group than in the CHF/dobutamine group, showing treatment differences by hazard ratio (HR) at days 5 (3.4 vs. 5.8%; HR, 0.58, CI 0.33–1.01, P = 0.05) and 14 (7.0 vs. 10.3%; HR, 0.67, CI 0.45–0.99, P = 0.045). For patients who used β-blockers (n = 669), mortality was significantly lower for levosimendan than dobutamine at day 5 (1.5 vs. 5.1% deaths; HR, 0.29; CI 0.11–0.78, P = 0.01). Conclusion Levosimendan may be better than dobutamine for treating patients with a history of CHF or those on β-blocker therapy when they are hospitalized with acute decompensations. These findings are preliminary but important for planning future studies.

A comparative study of the palliative care needs of heart failure and cancer patients

Abstract: Aims Studies 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 results This 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 Conclusion HF 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

Alcohol abuse and heart failure

Abstract: Alcoholic patients who consume >90 g of alcohol a day for >5 years are at risk of developing asymptomatic alcoholic cardiomyopathy (ACM). Those patients who continue to drink may become symptomatic and develop signs and symptoms of heart failure (HF). This distinct form of congestive HF is responsible for 21-36% of all cases of non-ischaemic dilated cardiomyopathy in Western Society. Without complete abstinence, the 4 year mortality for ACM is close to 50%. This short review summarizes the experimental and clinical evidence regarding the role of alcohol in the pathophysiology of ACM and HF.

A systematic review of telemonitoring technologies in heart failure.

Abstract: Aims Heart failure (HF) results in characteristic signs and symptoms including oedema and breathing difficulties. Heart failure is particularly suited to telemonitoring, because patients’ signs and symptoms can be assessed remotely by healthcare providers, and deterioration can be quickly detected and addressed. In this paper, we review studies conducted in HF telemonitoring, to describe the nature of the modality, the methods, and the results. Methods and results Articles were obtained through a MedLine search, utilizing the term heart failure in conjunction with the terms telehealth, telecare, telemonitoring, web, Internet, remote monitoring, and self-monitoring. Studies utilizing various modalities, including telephone touch pad, specialized hardware, and websites for participants to enter data were found, with various benefits being reported. Most studies demonstrated improvements in outcome measures, including improved quality of life and decreased hospitalizations. However, not all studies reported the same improvements and in several cases the sample sizes were relatively small. Conclusion Telemonitoring appears to be an acceptable method for monitoring of HF patients. Controlled, randomized studies directly comparing different modalities and evaluating their success and feasibility when used as part of routine clinical care, are now required.

Transplantation of mesenchymal stem cells within a poly(lactide-co-ɛ-caprolactone) scaffold improves cardiac function in a rat myocardial infarction model

Abstract: Aims Cardiac tissue engineering has been proposed as an appropriate method to repair myocardial infarction (MI). Evidence suggests that a cell with scaffold combination was more effective than a cell-only implant. Nevertheless, to date, there has been no research into elastic biodegradable poly(lactide-co-e-caprolactone) (PLCL) scaffolds. The aim of this study was to investigate the effect of mesenchymal stem cells (MSCs) with elastic biodegradable PLCL scaffold transplants in a rat MI model. Methods and results Ten days after inducing MI through the cryoinjury method, a saline control, MSC, PLCL scaffold, or MSC-seeded PLCL scaffold was transplanted onto the hearts. Four weeks after transplantation, cardiac function and histology were evaluated. Transplanted MSCs survived and differentiated into cardiomyocytes in the injured region. Left ventricular ejection fraction in the MSC + PLCL group increased by 23% compared with that in the saline group; it was also higher in the MSC group. The infarct area in the MSC + PLCL group was decreased by 29% compared with that in the saline group; it was also reduced in the MSC group. Conclusion Mesenchymal stem cells plus PLCL should be an excellent combination for cardiac tissue engineering.

Oxidative stress and hyperuricaemia: pathophysiology, clinical relevance, and therapeutic implications in chronic heart failure.

Abstract: Heart failure (HF) is a state of chronic deterioration of oxidative mechanisms due to enhanced oxidative stress and consequent subcellular alterations. In this condition, oxidant-producing enzymes, in particular xanthine oxidase (XO), the major cardiovascular source of reactive oxygen species (ROS), are up-regulated. Growing evidence shows that this impaired oxidative metabolism due to enhanced ROS release is implicated in the development of cardiac hypertrophy, myocardial fibrosis, left ventricular remodelling, and contractility impairment responsible for worsening of cardiac function in CHF. Uric acid (UA) has long been linked with cardiovascular diseases, and hyperuricaemia is a common finding in patients with CHF. Hyperuricaemia is associated with impairment of peripheral blood flow and reduced vasodilator capacity, which relate closely to clinical status and reduced exercise capacity. Recent studies also suggest an association between UA levels and parameters of diastolic function; more importantly, UA has emerged as a strong independent prognostic factor in patients with CHF. In this review, we describe the up-to-date experimental and clinical studies that have begun to test whether the inhibition of XO translates into meaningful beneficial pathophysiological changes. This treatment gives evidence that myocardial energy, endothelial dysfunction, and vasodilator reactivity to exercise are improved by reducing markers of oxidative stress responsible for vascular dysfunction, so it represents an interesting therapeutic alternative for better outcome in CHF patients.

Long-term prognosis of medically treated patients with functional mitral regurgitation and left ventricular dysfunction

Abstract: Aims To assess long-term prognosis in patients with functional mitral regurgitation (FMR) and left ventricular (LV) dysfunction, receiving current standard pharmacological therapy. Methods and results We prospectively enrolled 404 consecutive patients (mean age 70.2 ± 10 years) with ischaemic (76.5%) and non-ischaemic (23.5%) LV dysfunction (ejection fraction 34.4 ± 10.8%) and at least mild MR. Results are reported at 4 years' follow-up. Survival free of all-cause mortality was 53% and cardiac death was 74%. Survival free of all-cause mortality was 50% (95% CI 35–72) for patients with moderate MR, 49% (95% CI 27–65) for severe MR, and 64% (95% CI 47–78) for mild MR (P = 0.03). Survival free of cardiac death was 57% (95% CI 38–74) for patients with moderate MR, 55% (95% CI 30–77) for severe MR, and 94% (95% CI 59–98) for mild MR (P = 0.003). Moderate-to-severe MR [relative risk (RR) 2.7, 95% CI 1.2–6.1, P = 0.003] was an independent predictor of cardiac death but not of all-cause mortality. Survival free of heart failure (HF) was 32%. Survival free of HF was 20% (95% CI 17–35) for patients with moderate MR, 18% (95% CI 15–32) for severe MR, and 62% (95% CI 45–72) for mild MR (P = 0.0001). Moderate-to-severe MR (RR 3.2, 95% CI 1.9–5.2, P = 0.0001) was an independent predictor of HF. Conclusion The mortality and morbidity of patients with LV dysfunction and FMR remain high despite current standard pharmacological therapy. Moderate-to-severe MR is an independent predictor of cardiac death and HF.

Home telemonitoring in heart failure patients: the HHH study (Home or Hospital in Heart Failure).

Abstract: Aims The Home or Hospital in Heart failure (HHH) study was a European Community-funded, multinational, randomized controlled clinical trial, conducted in the UK, Poland, and Italy, to assess the feasibility of a new system of home telemonitoring (HT). The HT system was used to monitor clinical and physiological parameters, and its effectiveness (compared with usual care) in reducing cardiac events in heart failure (HF) patients was evaluated. Measurements were patient-managed. Methods and results From 2002 to 2004, 461 HF patients (age 60 ± 11 years, New York Heart Association class 2.4 ± 0.6, left ventricular ejection fraction 29 ± 7%) were enrolled at 11 centres and randomized (1:2) to either usual outpatient care or HT administered as three randomized strategies: (i) monthly telephone contact; (ii) strategy 1 plus weekly transmission of vital signs; and (iii) strategy 2 plus monthly 24 h recording of cardiorespiratory activity. Patients completed 81% of vital signs transmissions, as well as 92% of cardiorespiratory recordings. Over a 12-month follow-up, there was no significant effect of HT in reducing bed-days occupancy for HF or cardiac death plus HF hospitalization. Post hoc analysis revealed a heterogeneous effect of HT in the three countries with a trend towards a reduction of events in Italy. Conclusion Home or Hospital in Heart failure indicates that self-managed HT of clinical and physiological parameters is feasible in HF patients, with surprisingly high compliance. Whether HT contributes to a reduction of cardiac events requires further investigation.

A randomized trial of home telemonitoring in a typical elderly heart failure population in North West London: results of the Home-HF study

Abstract: Aims Heart failure chiefly affects the elderly, with frequent emergency admissions. Telemonitoring can identify worsening heart failure but previous randomized trials have enrolled selected patient populations. The Home-HF study examined the impact of home telemonitoring on typical heart failure patients discharged from three acute hospitals in North West London, UK.

Implementation of device therapy (cardiac resynchronization therapy and implantable cardioverter defibrillator) for patients with heart failure in Europe: changes from 2004 to 2008.

Abstract: Aims Heart failure (HF) patients increasingly receive device therapy, either an implantable cardioverter defibrillator (ICD) or a biventricular pacemaker, also called cardiac resynchronization therapy (CRT), or a CRT device with an ICD (CRT-D). However, epidemiological data on the use of device therapy in Europe are limited. Methods and results Data on implantation rates for conventional pacemakers, ICD, CRT, and CRT-D in 15 Western European countries were obtained from the Eucomed Registry for the 5-year period 2004–2008. Implantation of conventional pacemakers increased by 9% in Europe over the 5 years (reaching 907/million in 2008) and there were significant differences between countries. Implantable cardioverter defibrillator implantations increased by 75% from 80/million in 2004 to 140/million in 2008, and differences between countries were larger than those for conventional pacemakers. Implantation rates for CRT-P alone increased slightly from 2004 to 2006, but remained at 25/million thereafter in Europe overall. The total number of CRT implants (CRT-P and -D) markedly increased from 46/million in 2004 to 99/million in 2008 (115%), but this was mainly due to more CRT-D implants, i.e. an increase in the proportion of CRT-D (from 55% in 2004 to 75% in 2008). Implantation rates for ICD, CRT, and CRT-D remained markedly different throughout the study period between countries. Conclusion Implantation rates of devices for HF, in particular ICD and CRT-D, have increased significantly between 2004 and 2008 in Europe, but there remain major differences between countries.

Independent relationship of left atrial size and mortality in patients with heart failure: an individual patient meta-analysis of longitudinal data (MeRGE Heart Failure).

Abstract: Aims Left atrial (LA) size is considered a marker of poor prognosis in heart failure (HF) patients. Prior studies have recruited relatively few subjects limiting their power to adequately analyse the interaction between LA size, left ventricular (LV) systolic and diastolic function, and prognosis. Method and results The MeRGE collaboration combines prospective data from 18 studies in HF patients. In this analysis of data from 1157 patients, the primary endpoint was death or hospitalization for worsening HF. In multivariate analysis (Cox proportion hazard model), LA area was associated with prognosis (HR 1.03 per cm2, 95% CI 1.02, 1.05; P < 0.0001) independently of age, NYHA class, LV ejection fraction, and restrictive filling pattern (RFP). When LA area was used as a categorical variable, the HR associated with larger LA area (above median) was 1.4 (95% CI 1.13, 1.74) and when LA area index was used, the HR was 2.36 (95% CI 1.80, 3.08). When the patients with and without RFP were divided on the basis of either LA area or LA area index, significantly higher event rates were observed in those with larger LA area. Conclusion Left atrial area is a powerful predictor of outcome among HF patients with predominantly impaired systolic function, and is independent of, and provides additional prognostic information beyond LV systolic and diastolic function.

Septal rebound stretch reflects the functional substrate to cardiac resynchronization therapy and predicts volumetric and neurohormonal response.

Abstract: Aims To develop a novel myocardial deformation index that is highly sensitive to the effect of cardiac resynchronization therapy (CRT) and that can be used to predict response to CRT. Methods and results Before and 6.5 ± 2.3 months after implantation of a CRT device, longitudinal shortening and stretch were timed and quantified by speckle tracking echocardiography in a cohort of 62 patients. Distinction was made between systolic total stretch (STS; all systolic stretch) and systolic rebound stretch (SRS; only systolic stretch following initial shortening). Systolic total stretch and SRS could be measured in all wall segments in 41 of 62 patients. Septal SRS quantification was possible in all 62 patients and was performed by a blinded observer. Cardiac resynchronization therapy reduced STS (−55 ± 30%) but reduced SRS (−77 ± 21%) significantly more (P < 0.01). The largest amount of baseline SRS and the largest reductions in SRS (−90 ± 22%) were found in the septum. Reductions in local SRS were paralleled by increases in local systolic shortening that were twice as large (r = 0.79), thereby strongly improving septal function. Baseline values of septal SRS correlated with reductions in left ventricular end-systolic volume index (ΔLVESVi; r = 0.62) and brain-type natriuretic peptide (BNP) (Δlog10BNP; r = 0.57). Septal SRS was an independent predictor of CRT response in linear regression analysis and predicted ΔLVESVi of ≥15% with a sensitivity and specificity of 81% at ROC analysis (areas under the curve 0.89 ± 0.04). Conclusion Septal rebound stretch appears to be a sensitive and practical diagnostic criterion to quantify the functional substrate amenable to CRT and to predict response.

Predictors of fatal and non-fatal outcomes in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA): incremental value of apolipoprotein A-1, high-sensitivity C-reactive peptide and N-terminal pro B-type natriuretic peptide

Abstract: Aims Few prognostic models in heart failure have been developed in typically elderly patients treated with modern pharmacological therapy and even fewer included simple biochemical tests (such as creatinine), new biomarkers (such as natriuretic peptides), or, especially, both. In addition, most models have been developed for the single outcome of all-cause mortality. Methods and results We built a series of models for nine different fatal and non-fatal outcomes. For each outcome, a model was first built using demographic and clinical variables (Step 1), then with the addition of biochemical measures (serum creatinine, alanine aminotransferase, creatine kinase, thyrotrophin, apolipoproteins A-1 and B, and triglycerides) (Step 2) and finally with the incorporation of high-sensitivity C-reactive protein (hsCRP) and N-terminal pro B-type natriuretic peptide (NT-proBNP). Ranked according to the Wald χ2 value, age (56), ejection fraction (44), and body mass index (42) were most predictive of all-cause mortality in Step 1 (total model χ2 343). Creatinine was the most powerful predictor at Step 2 (48) and ApoA-1 ranked fifth (25), with the overall χ2 increasing to 440. Log NT-proBNP (167) was the most powerful of the 14 independently predictive variables identified at Step 3 and the overall χ2 increased to 600. NT-proBNP was the most powerful predictor of each other outcome. hsCRP was not a predictor of all-cause mortality but did predict the composite atherothrombotic outcome. Conclusion Of the two new biomarkers studied in prognostic models in heart failure, NT-proBNP, but not hsCRP, added substantial and independent predictive information, for a range of clinical outcomes, to that provided by simple demographic, clinical, and biochemical measures. ApoA-1 was more predictive than LDL or HDL.

The prognostic significance of heart failure with preserved left ventricular ejection fraction: a literature-based meta-analysis.

Abstract: Aims Heart failure (HF) with normal or preserved left ventricular (LV) ejection fraction (HFPEF) has been reported to be associated with similar outcome as HF with reduced EF (HFREF) in registry-based and epidemiological analyses, but many of these studies excluded patients who did not have EF measurements. Conversely, prior prospective studies have reported better outcome for patients with HFPEF. We performed a meta-analysis of prospective observational studies comparing all-cause mortality in patients with HFREF and HFPEF. Methods and results We searched several online databases for studies comparing outcome in HFREF and HFPEF, published before 2007. Inclusion criteria: prospective, clinical HF, near complete EF data, and mortality outcome. Review Manager version 4.2.3 software was used for the analysis. Overall, 24 501 patients [9299 deaths (38%)] from 17 studies are included. Average follow-up was 47 months; the HFPEF group was older (69 vs. 66 years) and more likely to be female (44% vs. 26%). Of the 7688 patients with HFPEF 2468 died (32.1%), compared with 6831 of the 16 813 patients with HFREF (40.6%): odds ratio 0.51 (95% CI: 0.48, 0.55). Conclusion This literature-based meta-analysis demonstrates that mortality among patients with HFPEF was half that observed in those with HFREF, in contrast to previous reports suggesting that mortality may be similar between both groups.

Design of the Reduction of Events with Darbepoetin alfa in Heart Failure (RED-HF): a Phase III, anaemia correction, morbidity-mortality trial

Abstract: Patients with heart failure (HF) and anaemia have greater functional impairment, worse symptoms, increased rates of hospital admission, and a higher risk of death, compared with non-anaemic HF patients. Whether correcting anaemia can improve outcomes is unknown. The Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF; Clinical Trials.gov NCT 003 58215) was designed to evaluate the effect of the long-acting erythropoietin-stimulating agent darbepoetin alfa on mortality and morbidity (and quality of life) in patients with HF and anaemia. Approximately 2600 patients with New York Heart Association class II-IV, an ejection fraction = 9.0 g/dL will be enrolled. Patients are randomized 1:1 to double-blind subcutaneous administration of darbepoetin alfa or placebo. Investigators are also blinded to Hb measurements and darbepoetin alfa is dosed to achieve an Hb concentration of 13.0 g/dL (but not exceeding 14.5 g/dL) with sham adjustments of the dose of placebo. The primary endpoint is the time to death from any cause or first hospital admission for worsening HF, whichever occurs first. The study will complete when similar to 1150 subjects experience a primary endpoint.

Impact of exercise training on myostatin expression in the myocardium and skeletal muscle in a chronic heart failure model

Abstract: Aims In late-stage chronic heart failure (CHF), elevated cytokines and cachexia are often observed. Several studies have shown that exercise training exerts beneficial effects on skeletal muscle in this setting. Furthermore, it has been shown that the expression of myostatin, a key regulator of skeletal muscle mass, is increased in a variety of cachectic states. This study aimed to investigate the expression of myostatin in CHF, the influence of exercise training on myostatin levels, and regulation of myostatin by tumour necrosis factor-α (TNF-α). Methods and results In an animal model of CHF (LAD-ligation model), protein expression of myostatin was elevated 2.4-fold in the skeletal muscle and more than four-times in the myocardium, compared with control (Co). Exercise training on a treadmill over 4 weeks led to a significant reduction in myostatin protein expression in the skeletal muscle and the myocardium of CHF animals, with values returning to baseline levels. In differentiated C2C12 cells, TNF-α induced the expression of myostatin through a p38MAPK-dependent pathway involving nuclear factor kappa-B (NF-κB). The increased TNF-α mRNA levels in the skeletal muscle of CHF animals correlated significantly with myostatin expression. Conclusion These alterations in myostatin expression in the skeletal and heart muscle following exercise training could help to explain the beneficial anti-catabolic effects of exercise training in CHF.