Heart rate and blood pressure monitoring in heart failure.

It has been long known that incessant tachycardia and severe hypertension can cause heart failure (HF). In recent years, it has also been recognized that more modest elevations in either heart rate (HR) or blood pressure (BP), if sustained, can be a risk factor both for the development of HF and for mortality in patients with established HF. Heart rate and BP are thus both modifiable risk factors in the setting of HF. What is less clear is the question whether routine systematic monitoring of these simple physiological parameters to a target value can offer clinical benefits. Measuring these parameters clinically during patient review is recommended in HF management in most HF guidelines, both in the acute and chronic phases of the disease. More sophisticated systems now allow long-term automatic or remote monitoring of HR and BP and whether this more detailed patient information can improve clinical outcomes will require prospective RCTs to evaluate. In addition, analysis of patterns of both HR and BP variability can give insights into autonomic function, which is also frequently abnormal in HF. This window into autonomic dysfunction in our HF patients can also provide further independent prognostic information and may in itself be target for future interventional therapies. This article, developed during a consensus meeting of the Heart Failure Association of the ESC concerning the role of physiological monitoring in the complex multi-morbid HF patient, highlights the importance of repeated assessment of HR and BP in HF, and reviews gaps in our knowledge and potential future directions

Physiological monitoring in the complex multimorbid heart failure patient - Conclusions.

Comorbidities are increasingly recognized as crucial components of the heart failure syndrome. Main specific challenges are polypharmacy, poor adherence to treatments, psychological aspects, and the need of monitoring after discharge. The chronic multimorbid patient therefore represents a specific heart failure phenotype that needs an appropriate and continuous management over time. This supplement issue covers the key points of a series of meeting coordinated by the Heart Failure Association of the European Society of Cardiology (ESC), that have discussed the issues surrounding the effective monitoring of our ever more complex and multimorbid heart failure patients. Here, we present an overview of the complex issues from a healthcare delivery perspective

Exercise-based rehabilitation for heart failure (review)

Meta-AnalysisReviewThis is the final version of the article. Available from the Cochrane Collaboration via the DOI in this record.BACKGROUND: Previous systematic reviews and meta-analyses consistently show the positive effect of exercise-based rehabilitation for heart failure (HF) on exercise capacity; however, the direction and magnitude of effects on health-related quality of life, mortality and hospital admissions in HF remain less certain. This is an update of a Cochrane systematic review previously published in 2010. OBJECTIVES: To determine the effectiveness of exercise-based rehabilitation on the mortality, hospitalisation admissions, morbidity and health-related quality of life for people with HF. Review inclusion criteria were extended to consider not only HF due to reduced ejection fraction (HFREF or 'systolic HF') but also HF due to preserved ejection fraction (HFPEF or 'diastolic HF'). SEARCH METHODS: We updated searches from the previous Cochrane review. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue1, 2013) from January 2008 to January 2013. We also searched MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO) and PsycINFO (Ovid) (January 2008 to January 2013). We handsearched Web of Science, bibliographies of systematic reviews and trial registers (Controlled-trials.com and Clinicaltrials.gov). SELECTION CRITERIA: Randomised controlled trials of exercise-based interventions with six months' follow-up or longer compared with a no exercise control that could include usual medical care. The study population comprised adults over 18 years and were broadened to include individuals with HFPEF in addition to HFREF. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all identified references and rejected those that were clearly ineligible. We obtained full-text papers of potentially relevant trials. One review author independently extracted data from the included trials and assessed their risk of bias; a second review author checked data. MAIN RESULTS: We included 33 trials with 4740 people with HF predominantly with HFREF and New York Heart Association classes II and III. This latest update identified a further 14 trials. The overall risk of bias of included trials was moderate. There was no difference in pooled mortality between exercise-based rehabilitation versus no exercise control in trials with up to one-year follow-up (25 trials, 1871 participants: risk ratio (RR) 0.93; 95% confidence interval (CI) 0.69 to 1.27, fixed-effect analysis). However, there was trend towards a reduction in mortality with exercise in trials with more than one year of follow-up (6 trials, 2845 participants: RR 0.88; 95% CI 0.75 to 1.02, fixed-effect analysis). Compared with control, exercise training reduced the rate of overall (15 trials, 1328 participants: RR 0.75; 95% CI 0.62 to 0.92, fixed-effect analysis) and HF specific hospitalisation (12 trials, 1036 participants: RR 0.61; 95% CI 0.46 to 0.80, fixed-effect analysis). Exercise also resulted in a clinically important improvement superior in the Minnesota Living with Heart Failure questionnaire (13 trials, 1270 participants: mean difference: -5.8 points; 95% CI -9.2 to -2.4, random-effects analysis) - a disease specific health-related quality of life measure. However, levels of statistical heterogeneity across studies in this outcome were substantial. Univariate meta-regression analysis showed that these benefits were independent of the participant's age, gender, degree of left ventricular dysfunction, type of cardiac rehabilitation (exercise only vs. comprehensive rehabilitation), mean dose of exercise intervention, length of follow-up, overall risk of bias and trial publication date. Within these included studies, a small body of evidence supported exercise-based rehabilitation for HFPEF (three trials, undefined participant number) and when exclusively delivered in a home-based setting (5 trials, 521 participants). One study reported an additional mean healthcare cost in the training group compared with control of USD3227/person. Two studies indicated exercise-based rehabilitation to be a potentially cost-effective use of resources in terms of gain in quality-adjusted life years (QALYs) and life-years saved. AUTHORS' CONCLUSIONS: This updated Cochrane review supports the conclusions of the previous version of this review that, compared with no exercise control, exercise-based rehabilitation does not increase or decrease the risk of all-cause mortality in the short term (up to 12-months' follow-up) but reduces the risk of hospital admissions and confers important improvements in health-related quality of life. This update provides further evidence that exercise training may reduce mortality in the longer term and that the benefits of exercise training on appear to be consistent across participant characteristics including age, gender and HF severity. Further randomised controlled trials are needed to confirm the small body of evidence seen in this review for the benefit of exercise in HFPEF and when exercise rehabilitation is exclusively delivered in a home-based setting

Exercise-based rehabilitation for heart failure: systematic review and meta-analysis

This is the final version of the article. Available from BMJ Publishing Group via the DOI in this record.OBJECTIVE: To update the Cochrane systematic review of exercise-based cardiac rehabilitation (CR) for heart failure. METHODS: A systematic review and meta-analysis of randomised controlled trials was undertaken. MEDLINE, EMBASE and the Cochrane Library were searched up to January 2013. Trials with 6 or more months of follow-up were included if they assessed the effects of exercise interventions alone or as a component of comprehensive CR programme compared with no exercise control. RESULTS: 33 trials were included with 4740 participants predominantly with a reduced ejection fraction (<40%) and New York Heart Association class II and III. Compared with controls, while there was no difference in pooled all-cause mortality between exercise CR with follow-up to 1 year (risk ratio (RR) 0.93; 95% CI 0.69 to 1.27, p=0.67), there was a trend towards a reduction in trials with follow-up beyond 1 year (RR 0.88; 0.75 to 1.02, 0.09). Exercise CR reduced the risk of overall (RR 0.75; 0.62 to 0.92, 0.005) and heart failure-specific hospitalisation (RR 0.61; 0.46 to 0.80, 0.0004) and resulted in a clinically important improvement in the Minnesota Living with Heart Failure questionnaire (mean difference: -5.8 points, -9.2 to -2.4, 0.0007). Univariate meta-regression analysis showed that these benefits were independent of the type and dose of exercise CR, and trial duration of follow- up, quality or publication date. CONCLUSIONS: This updated Cochrane review shows that improvements in hospitalisation and health-related quality of life with exercise-based CR appear to be consistent across patients regardless of CR programme characteristics and may reduce mortality in the longer term. An individual participant data meta-analysis is needed to provide confirmatory evidence of the importance of patient subgroup and programme level characteristics (eg, exercise dose) on outcome.This publication presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-1210-12004)

An expert opinion paper on statin adherence and implementation of new lipid-lowering medications by the ESC Working Group on Cardiovascular Pharmacotherapy: Barriers to be overcome.

Benefits and safety on statins have been well-established over 20 years of research. Despite this, the vast majority of patients are not adequately treated and do not achieve the low-density lipoprotein cholesterol target levels. This is mainly due to poor adherence, which is associated with dangerous and sometimes fatal outcomes. To increase adherence and prevent worse outcomes, a combination therapy with lower dosage of statins and new lipid-lowering drugs may be used. However, the implementation of new lipid-lowering drugs in European countries is still at the beginning. For these reasons, the aim of this position paper is to give an up-to-date indication from the ESC Working Group on Cardiovascular Pharmacotherapy in order to discuss the barriers towards statins adherence and new lipid-lowering drugs implementation in Europe

An international Delphi consensus regarding best practice recommendations for hyperkalaemia across the cardiorenal spectrum.

AIMS: Renin-angiotensin-aldosterone system inhibitors (RAASi) are guideline-recommended therapy for individuals with cardiorenal disease. They are associated with increased risk of hyperkalaemia, a common and life-threatening disorder for this population. RAASi-induced hyperkalaemia often leads to dose reduction or discontinuation, reducing cardiorenal protection. Guideline recommendations differ between specialties for the clinical management of hyperkalaemia. Using a modified Delphi method, we developed consensus recommendations for optimal management of hyperkalaemia in adults with cardiorenal disease. METHODS AND RESULTS: An international steering group of cardiologists and nephrologists developed 39 statements regarding hyperkalaemia care, including risk factors and risk stratification, prevention, correction, and cross-specialty coordination. Consensus was determined by agreement on an online questionnaire administered to cardiorenal specialists across Europe and North America. The threshold for consensus agreement was established a priori by the steering group at 67%. Across November 2021, 520 responses were received from Canada (n = 50), France (n = 50), Germany (n = 54), Italy (n = 58), Spain (n = 57), the UK (n = 49), and the US (n = 202); 268 from cardiologists and 252 from nephrologists. Twenty-nine statements attained very high agreement (≥90%) and 10 attained high agreement (≥67%-<90%), with strong alignment between cardiologists and nephrologists. CONCLUSION: A high degree of consensus regarding hyperkalaemia evaluation and management exists among healthcare professionals. Based on high levels of agreement, the steering group derived six key recommendations for hyperkalaemia prevention and management in people with cardiorenal disease. Future studies examining the quality of hyperkalaemia care delivery are required

Clinical and economic impact of ferric carboxymaltose treatment for iron deficiency in patients stabilized following acute heart failure: a multinational study.

OBJECTIVE: To estimate clinical events and evaluate the financial implications of introducing ferric carboxymaltose (FCM) to treat iron deficiency (ID) at discharge in patients hospitalized for acute heart failure (AHF) with left ventricular ejection fraction (LVEF) <50% in the UK, Switzerland and Italy. METHODS: A decision analytic cost-offset model was developed to evaluate the costs associated with introducing FCM for all eligible patients in three countries compared to a world without FCM, over a five-year time horizon. Data from AFFIRM-AHF clinical trial were used to model clinical outcomes, using an established cohort state-transition Markov model. Country-specific prevalence estimates were derived using data from real-world studies to extrapolate number of events and consequent cost totals to the population at risk on a national scale. RESULTS: The cost-offset modeling demonstrated that FCM is projected to be a cost-saving intervention in all three country settings over a five-year time horizon. Savings were driven primarily by reduced hospitalizations and avoided cardiovascular deaths, with net cost savings of -£14,008,238, -CHF25,456,455 and -€105,295,146 incurred to the UK, Switzerland and Italy, respectively. LIMITATIONS: Although AFFIRM-AHF was a multinational trial, efficacy data per country was not sufficiently large to enable country-specific analysis, therefore overall clinical parameters have been assumed to apply to all countries. CONCLUSIONS: This study provides further evidence of the potential cost savings achievable by treating ID with FCM at discharge in patients hospitalized for AHF with LVEF <50%. The value of FCM treatment within the healthcare systems of the UK, Switzerland and Italy was demonstrated even within a limited time frame of one year, with consistent cost savings indicated over a longer term

Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure.

BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS: Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction

Ferric carboxymaltose for the treatment of iron deficiency in heart failure: a multinational cost-effectiveness analysis utilising AFFIRM-AHF.

AIMS: Iron deficiency is common in patients with heart failure (HF). In AFFIRM-AHF, ferric carboxymaltose (FCM) reduced the risk of hospitalisations for HF (HHF) and improved quality of life vs. placebo in iron-deficient patients with a recent episode of acute HF. The objective of this study was to estimate the cost-effectiveness of FCM compared with placebo in iron-deficient patients with left ventricular ejection fraction <50%, stabilised after an episode of acute HF, using data from the AFFIRM-AHF trial from Italian, UK, US and Swiss payer perspectives. METHODS AND RESULTS: A lifetime Markov model was built to characterise outcomes in patients according to the AFFIRM-AHF trial. Health states were defined using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Subsequent HHF were incorporated using a negative binomial regression model with cardiovascular and all-cause mortality incorporated via parametric survival analysis. Direct healthcare costs (2020 GBP/USD/EUR/CHF) and utility values were sourced from published literature and AFFIRM-AHF. Modelled outcomes indicated that treatment with FCM was dominant (cost saving with additional health gains) in the UK, USA and Switzerland, and highly cost-effective in Italy [incremental cost-effectiveness ratio (ICER) EUR 1269 per quality-adjusted life-year (QALY)]. Results were driven by reduced costs for HHF events combined with QALY gains of 0.43-0.44, attributable to increased time in higher KCCQ states (representing better functional outcomes). Sensitivity and subgroup analyses demonstrated data robustness, with the ICER remaining dominant or highly cost-effective under a wide range of scenarios, including increasing treatment costs and various patient subgroups, despite a moderate increase in costs for de novo HF and smaller QALY gains for ischaemic aetiology. CONCLUSION: Ferric carboxymaltose is estimated to be a highly cost-effective treatment across countries (Italy, UK, USA and Switzerland) representing different healthcare systems

'Time is prognosis' in heart failure: time-to-treatment initiation as a modifiable risk factor.

In heart failure (HF), acute decompensation can occur quickly and unexpectedly because of worsening of chronic HF or to new-onset HF diagnosed for the first time ('de novo'). Patients presenting with acute HF (AHF) have a poor prognosis comparable with those with acute myocardial infarction, and any delay of treatment initiation is associated with worse outcomes. Recent HF guidelines and recommendations have highlighted the importance of a timely diagnosis and immediate treatment for patients presenting with AHF to decrease disease progression and improve prognosis. However, based on the available data, there is still uncertainty regarding the optimal 'time-to-treatment' effect in AHF. Furthermore, the immediate post-worsening HF period plays an important role in clinical outcomes in HF patients after hospitalization and is known as the 'vulnerable phase' characterized by high risk of readmission and early death. Early and intensive treatment for HF patients in the 'vulnerable phase' might be associated with lower rates of early readmission and mortality. Additionally, in the chronic stable HF outpatient, treatments are often delayed or not initiated when symptoms are stable, ignoring the risk for adverse outcomes such as sudden death. Consequently, there is a dire need to better identify HF patients during hospitalization and after discharge and treating them adequately to improve their prognosis. HF is an urgent clinical scenario along all its stages and disease conditions. Therefore, time plays a significant role throughout the entire patient's journey. Therapy should be optimized as soon as possible, because this is beneficial regardless of severity or duration of HF. Time lavished before treatment initiation is recognized as important modifiable risk factor in HF