Left ventricular ejection fraction (EF) remains the major parameter for diagnosis, phenotyping, prognosis and treatment decisions in heart failure. The 2016 ESC heart failure guidelines introduced a ...third EF category for an EF of 40-49%, defined as heart failure with mid-range EF (HFmrEF). This category has been largely unexplored compared with heart failure with reduced EF (HFrEF; defined as EF <40% in this Review) and heart failure with preserved EF (HFpEF; defined as EF ≥50%). The prevalence of HFmrEF within the overall population of patients with HF is 10-25%. HFmrEF seems to be an intermediate clinical entity between HFrEF and HFpEF in some respects, but more similar to HFrEF in others, in particular with regard to the high prevalence of ischaemic heart disease in these patients. HFmrEF is milder than HFrEF, and the risk of cardiovascular events is lower in patients with HFmrEF or HFpEF than in those with HFrEF. By contrast, the risk of non-cardiovascular adverse events is similar or greater in patients with HFmrEF or HFpEF than in those with HFrEF. Evidence from post hoc and subgroup analyses of randomized clinical trials and a trial of an SGLT1-SGLT2 inhibitor suggests that drugs that are effective in patients with HFrEF might also be effective in patients with HFmrEF. Although the EF is a continuous measure with considerable variability, in this comprehensive Review we suggest that HFmrEF is a useful categorization of patients with HF and shares the most important clinical features with HFrEF, which supports the renaming of HFmrEF to HF with mildly reduced EF.
Heart Failure (HF) is a multi-faceted and life-threatening syndrome characterized by significant morbidity and mortality, poor functional capacity and quality of life, and high costs. HF affects more ...than 64 million people worldwide. Therefore, attempts to decrease its social and economic burden have become a major global public health priority. While the incidence of HF has stabilized and seems to be declining in industrialized countries, the prevalence is increasing due to the ageing of the population, improved treatment of and survival with ischaemic heart disease, and the availability of effective evidence-based therapies prolonging life in patients with HF. There are geographical variations in HF epidemiology. There is substantial lack of data from developing countries, where HF exhibits different features compared with that observed in the Western world. In this review, we provide a contemporary overview on the global burden of HF, providing updated estimates on prevalence, incidence, outcomes, and costs worldwide.
Despite guideline recommendations and available evidence, implementation of treatment in heart failure (HF) is poor. The majority of patients are not prescribed drugs at target doses that have been ...proven to positively impact morbidity and mortality. Among others, tolerability issues related to low blood pressure, heart rate, impaired renal function or hyperkalaemia are responsible. Chronic kidney disease plays an important role as it affects up to 50% of patients with HF. Also, dynamic changes in estimated glomerular filtration rate may occur during the course of HF, resulting in inappropriate dose reduction or even discontinuation of decongestive or neurohormonal modulating therapy in clinical practice. As patients with HF are rarely naïve to pharmacologic therapies, the challenge is to adequately prioritize or select the most appropriate up‐titration schedule according to patient profile. In this consensus document, we identified nine patient profiles that may be relevant for treatment implementation in HF patients with a reduced ejection fraction. These profiles take into account heart rate (<60 bpm or >70 bpm), the presence of atrial fibrillation, symptomatic low blood pressure, estimated glomerular filtration rate (<30 or >30 mL/min/1.73 m2) or hyperkalaemia. The pre‐discharge patient, frequently still congestive, is also addressed. A personalized approach, adjusting guideline‐directed medical therapy to patient profile, may allow to achieve a better and more comprehensive therapy for each individual patient than the more traditional, forced titration of each drug class before initiating treatment with the next.
Aims
Use and dosing of guideline‐directed medical therapy (GDMT) in patients with heart failure (HF) have been shown to be suboptimal. Among new users of GDMT in HF, we followed the real‐life ...patterns of dose titration and discontinuation of angiotensin‐converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), beta‐blockers, mineralocorticoid receptor antagonists (MRA) and angiotensin receptor–neprilysin inhibitors (ARNI).
Methods and results
New users were identified in health care databases in Sweden, UK and US between 2016–2019. Inclusion criterion was a recent HF hospitalization (HHF) triggering the initiation of GDMT. Patients were grouped by GDMT, i.e. ACEi, ARB, beta‐blocker, MRA and ARNI, and stratified by initial dose. Follow‐up was 12 months, until death or study end. Outcomes were dose titration within each drug class, discontinuation and first HHF or death. Dose/discontinuation follow‐up was assessed daily based on the coverage length of a filled prescription and reported on day 365. New users of ACEi (n = 8426), ARB (n = 2303), beta‐blockers (n = 10 476), MRA (n = 17 421), and ARNI (n = 29 546) were identified. Over 12 months, target dose achievement was 15%, 10%, 12%, 30%, and discontinuation was 55%, 33%, 24% and 27% for ACEi, ARB, beta‐blockers and ARNI, respectively. MRA was rarely titrated and discontinuation rates were high (40%). Event rates for HHF or death ranged from 40.0–86.9 per 100 patient‐years across the treatment groups.
Conclusion
Despite high risk of clinical events following HHF, new initiation of GDMT was followed by consistent patterns of low up‐titration and early GDMT discontinuation in three countries with different health care and economies. Our data highlight the urgent need for moving away from long sequential approach when initiating HF treatment and for improving just‐in‐time decision support for patients and health care providers.
New users were identified in health care databases in Sweden, UK and US between 2016–2019. Inclusion criterion was a recent HHF triggering the initiation of GDMT. Patients were grouped by GDMT, i.e. ACEi, ARB, beta‐blocker, MRA and ARNI, and stratified by initial dose. Follow‐up was 12 months, until death or end of the registry. Outcomes were dose titration within each drug class, discontinuation and first HHF or all‐cause death. Dose/discontinuation follow‐up was assessed daily based on the coverage length of a filled prescription and reported on day 365. Due to the different structure of the registries used for the current analysis, the time‐windows adopted for identifying previous use of the drug differed across the three countries. In particular, in UK and Sweden the filled prescriptions for the treatments were checked since 2013 and 2014, respectively, i.e. wash‐out of 3 and 2 years, respectively, whereas in the US it was limited to 6 months. The 1‐year longer wash‐out in UK vs. Sweden was due to the fact that UK patients living in rural areas often receive prescriptions once/twice yearly covering the entire year rather than monthly, and therefore a longer wash‐out period was deemed necessary. Even shorter wash‐out in the US was due to the frequent changes in healthcare insurance providers, which would have led to a limited number of patients with data available 2 or 3 years prior to HHF. Furthermore, recent HHF was defined as 7 days prior to the initiation of GDMT in Sweden and US, but prior to 30 days in UK where patients are typically provided with 1‐month drug supply at discharge.
Objectives The goal of the study was to assess the effects of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) on the composite of cardiovascular (CV) death, ...myocardial infarction (MI), and stroke, and on all-cause death, new-onset heart failure (HF), and new-onset diabetes mellitus (DM) in high-risk patients without HF. Background ACE-Is reduce CV events in high-risk patients without HF whereas the effects of ARBs are less certain. Methods Twenty-six randomized trials comparing ARBs or ACE-Is versus placebo in 108,212 patients without HF were collected in a meta-analysis and analyzed for the risk of the composite outcome, all-cause death, new-onset HF, and new-onset DM. Results ACE-Is significantly reduced the risk of the composite outcome (odds ratio OR: 0.830 95% confidence interval (CI): 0.744 to 0.927; p = 0.001), MI (OR: 0.811 95% CI: 0.748 to 0.879; p < 0.001), stroke (OR: 0.796 95% CI: 0.682 to 0.928; p < 0.004), all-cause death (OR: 0.908 95% CI: 0.845 to 0.975; p = 0.008), new-onset HF (OR: 0.789 95% CI: 0.686 to 0.908; p = 0.001), and new-onset DM (OR: 0.851 95% CI: 0.749 to 0.965; p < 0.012). ARBs significantly reduced the risk of the composite outcome (OR: 0.920 95% CI: 0.869 to 0.975, p = 0.005), stroke (OR: 0.900 95% CI: 0.830 to 0.977, p = 0.011), and new-onset DM (OR: 0.855 95% CI: 0.798 to 0.915; p < 0.001). Conclusions In patients at high CV risk without HF, ACE-Is and ARBs reduced the risk of the composite outcome of CV death, MI, and stroke. ACE-Is also reduced the risk of all-cause death, new-onset HF, and new-onset DM. Thus, ARBs represent a valuable option to reduce CV mortality and morbidity in patients in whom ACE-Is cannot be used.
Guidelines recommend early initiation of multiple guideline-directed medical therapies (GDMTs) to reduce mortality/rehospitalization in patients with heart failure and reduced ejection fraction. ...Understanding GDMT use is critical to improving clinical practice.
This study sought to describe GDMT use in Japan, Sweden, and the United States in contemporary real-world settings.
EVOLUTION HF (Utilization of Dapagliflozin and Other Guideline Directed Medical Therapies in Heart Failure Patients: A Multinational Observational Study Based on Secondary Data) is an observational cohort study using routine-care databases. Patients initiating any GDMT within 12 months of a hospitalization for heart failure (hHF) discharge were included. Dapagliflozin (the only sodium-glucose cotransporter-2 inhibitor approved at study onset), sacubitril/valsartan, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) were considered separately. Doses and discontinuation were assessed in the 12 months following initiation. Target dose was defined as ≥100% of the guideline-recommended dose.
Overall, 266,589 patients were included. Mean times from hHF to GDMT initiation were longer for novel GDMTs (dapagliflozin or sacubitril/valsartan) than for other GDMTs: 39 and 44 vs 12 to 13 days (Japan), 44 and 33 vs 22 to 31 days (Sweden), and 33 and 19 vs 18 to 24 days (United States). Pooled across countries, proportions of patients who discontinued therapy (not including switches from ACE inhibitor or ARB to sacubitril/valsartan) within 12 months were 23.5% (dapagliflozin), 26.4% (sacubitril/valsartan), 38.4% (ACE inhibitors), 33.4% (ARBs), 25.2% (beta-blockers), and 42.2% (MRAs). Corresponding target dose achievements were 75.7%, 28.2%, 20.1%, 6.7%, 7.2%, and 5.1%, respectively.
Initiation of novel GDMTs is delayed compared with other GDMTs. Few patients received target doses of GDMTs requiring uptitration. Persistence was higher for dapagliflozin than other GDMTs.
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Aims
The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) developed the HFA Atlas to provide a contemporary description of heart failure (HF) epidemiology, resources, ...reimbursement of guideline‐directed medical therapy (GDMT) and activities of the National Heart Failure Societies (NHFS) in ESC member countries.
Methods and results
The HFA Atlas survey was conducted in 2018–2019 in 42 ESC countries. The quality and completeness of source data varied across countries. The median incidence of HF was 3.20 interquartile range (IQR) 2.66–4.17 cases per 1000 person‐years, ranging from ≤2 in Italy and Denmark to >6 in Germany. The median HF prevalence was 17.20 (IQR 14.30–21) cases per 1000 people, ranging from ≤12 in Greece and Spain to >30 in Lithuania and Germany. The median number of HF hospitalizations was 2671 (IQR 1771–4317) per million people annually, ranging from <1000 in Latvia and North Macedonia to >6000 in Romania, Germany and Norway. The median length of hospital stay for an admission with HF was 8.50 (IQR 7.38–10) days. Diagnostic and management resources for HF varied, with high‐income ESC member countries having substantially more resources compared with middle‐income countries. The median number of hospitals with dedicated HF centres was 1.16 (IQR 0.51–2.97) per million people, ranging from <0.10 in Russian Federation and Ukraine to >7 in Norway and Italy. Nearly all countries reported full or partial reimbursement of standard GDMT, except ivabradine and sacubitril/valsartan. Almost all countries reported having NHFS or working groups and nearly half had HF patient organizations.
Conclusions
The first report from the HFA Atlas has shown considerable heterogeneity in HF disease burden, the resources available for its management and data quality across ESC member countries. The findings emphasize the need for a systematic approach to the capture of HF statistics so that inequalities and improvements in care may be quantified and addressed.
Sodium-glucose transporter-2 inhibitors (SGLT2i), originally launched as glucose-lowering drugs, have been studied in large cardiovascular outcome trials to ascertain safety. Surprisingly, these ...compounds reduced the risk of cardiovascular events (cardiovascular death, non-fatal myocardial and non-fatal stroke) and total mortality. The mechanisms behind this benefit are only partly understood, but a major contributor is the reduction of heart failure hospitalisations, evident already within weeks after the initiation of the SGLT2i.
SGLT2 inhibition increases urinary glucose excretion, thereby improving glycaemic control in an insulin-independent manner. Moreover, SGLT2i potentially impact the cardiovascular system both indirectly via weight loss and blood pressure lowering and directly through osmotic diuresis and increased sodium excretion and presumably by improving myocardial energetics.
The aim of this review is to summarise evidence from all major outcome trials investigating SGLT2i in patients with diabetes, as well as recent evidence from trials in heart failure patients without glucose perturbations, which pave the way for novel treatment of large groups of patients.
The results of these studies have been taken into account in recently issued guidelines for the management of diabetes and cardiovascular disease. An important task for diabetologists, cardiologists and general practitioners is to incorporate them into clinical practice to the benefit of many patients.
The role of metabolic syndrome in heart failure Perrone-Filardi, Pasquale; Paolillo, Stefania; Costanzo, Pierluigi ...
European heart journal,
10/2015, Letnik:
36, Številka:
39
Journal Article
Recenzirano
Odprti dostop
Metabolic syndrome (MS) is a highly prevalent condition in patients affected by heart failure (HF); however, it is still unclear whether, in the setting of cardiac dysfunction, it represents an ...adverse risk factor for the occurrence of cardiac events. The epidemiologic implications of MS in HF have been studied intensely, as many of its components contribute to the incidence and severity of HF. In particular, insulin resistance, diabetes mellitus, and lipid abnormalities represent the main components that negatively influence disease progression and evolution. Yet, other components of the MS, i.e. overweight/obesity and high blood pressure, are favourably associated with outcome in HF patients. The aim of this review was to report epidemiology and prognostic role of MS in HF and to investigate current clinical implications and future research needs.
This study sought to evaluate the incidence, the predictors, and the associations with outcomes of changes in ejection fraction (EF) in heart failure (HF) patients.
EF determines therapy in HF, but ...information is scarce about incidence, determinants, and prognostic implications of EF change over time.
Patients with ≥2 EF measurements registered in the Swedish Heart Failure Registry were categorized as heart failure with preserved ejection fraction (HFpEF) (EF ≥50%), heart failure with midrange ejection fraction (HFmrEF) (EF 40% to 49%), or heart failure with reduced ejection fraction (HFrEF) (EF <40%). Changes among categories were recorded, and associations among EF changes, predictors, and all-cause mortality and/or HF hospitalizations were analyzed using logistic and Cox regressions.
Of 4,942 patients at baseline, 18% had HFpEF, 19% had HFmrEF, and 63% had HFrEF. During follow-up, 21% and 18% of HFpEF patients transitioned to HFmrEF and HFrEF, respectively; 37% and 25% of HFmrEF patients transitioned to HFrEF and HFpEF, respectively; and 16% and 10% of HFrEF patients transitioned to HFmrEF and HFpEF, respectively. Predictors of increased EF included female sex, cases of less severe HF, and comorbidities. Predictors of decreased EF included diabetes, ischemic heart disease, and cases of more severe HF. Use of renin-angiotensin-system inhibitors was associated with lower likelihood of EF increase, but not with EF decrease (i.e., stable EF). Increased EF was associated with a lower risk (hazard ratio HR: 0.62; 95% confidence interval CI: 0.55 to 0.69) and decreased EF with a higher risk (HR: 1.15; 95% CI: 1.01 to 1.30) of mortality and/or HF hospitalizations. Prognostic implications were most evident for transitions to and from HFrEF.
Increases in EF occurred in one-fourth of HFrEF and HFmrEF patients, and decreases occurred in more than one-third of patients with HFpEF and HFmrEF. EF change was associated with a wide range of important clinical and organizational factors as well as with outcomes, particularly transitions to and from HFrEF.
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