Cause-specific death in heart failure across the ejection fraction spectrum: A comprehensive assessment of over 100 000 patients in the Swedish Heart Failure Registry.

AIM: To assess cause-specific death in patients with heart failure with preserved, mildly reduced, and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF). METHODS AND RESULTS: Data were analysed from the Swedish Heart Failure Registry (SwedeHF) and the National Patient Register of patients enrolled in SwedeHF 2000-2021. Cox proportional hazards regression models were performed and adjusted for age, sex and time period. Among 100 584 patients (23% HFpEF, 23% HFmrEF, 53% HFrEF), median age (interquartile range) was 75 (66-82) and 36% were female. Of those who died within 5 years, most deaths were ascribed to cardiovascular (CV) causes across all ejection fraction (EF) categories. Within 5 years, HFpEF had higher adjusted risk of non-CV death (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.28-1.38, p < 0.001) and lower adjusted risk of CV death (HR 0.85, 95% CI 0.82-0.88, p < 0.001) compared to HFrEF. Ischaemic heart disease (IHD) and cancer were the most common causes of CV and non-CV death regardless of EF category. The incidence rate of CV death due to IHD was highest in HFrEF while incidence rates of CV death due to pulmonary vascular disease, stroke, valvular heart disease and atrial fibrillation increased with increasing EF. The incidence rates of non-CV deaths due to cancer, respiratory disease, and infections increased with increasing EF. CONCLUSION: Cardiovascular death was more common than non-CV death across all EF categories although the risk of non-CV death within 5 years was higher with increasing EF. IHD and cancer were the most common causes of CV and non-CV deaths, respectively, regardless of EF category.

Epidemiology, pathophysiology, diagnosis and management of chronic right-sided heart failure and tricuspid regurgitation. A clinical consensus statement of the Heart Failure Association (HFA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC.

Right-sided heart failure and tricuspid regurgitation are common and strongly associated with poor quality of life and an increased risk of heart failure hospitalizations and death. While medical therapy for right-sided heart failure is limited, treatment options for tricuspid regurgitation include surgery and, based on recent developments, several transcatheter interventions. However, the patients who might benefit from tricuspid valve interventions are yet unknown, as is the ideal time for these treatments given the paucity of clinical evidence. In this context, it is crucial to elucidate aetiology and pathophysiological mechanisms leading to right-sided heart failure and tricuspid regurgitation in order to recognize when tricuspid regurgitation is a mere bystander and when it can cause or contribute to heart failure progression. Notably, early identification of right heart failure and tricuspid regurgitation may be crucial and optimal management requires knowledge about the different mechanisms and causes, clinical course and presentation, as well as possible treatment options. The aim of this clinical consensus statement is to summarize current knowledge about epidemiology, pathophysiology and treatment of tricuspid regurgitation in right-sided heart failure providing practical suggestions for patient identification and management.

Incidence, risk assessment and prevention of sudden cardiac death in cardiomyopathies.

Cardiomyopathies are a significant contributor to cardiovascular morbidity and mortality, mainly due to the development of heart failure and increased risk of sudden cardiac death (SCD). Despite improvement in survival with contemporary treatment, SCD remains an important cause of mortality in cardiomyopathies. It occurs at a rate ranging between 0.15% and 0.7% per year (depending on the cardiomyopathy), which significantly surpasses SCD incidence in the age- and sex-matched general population. The risk of SCD is affected by multiple factors including the aetiology, genetic basis, age, sex, physical exertion, the extent of myocardial disease severity, conduction system abnormalities, and electrical instability, as measured by various metrics. Over the past decades, the knowledge on the mechanisms and risk factors for SCD has substantially improved, allowing for a better-informed risk stratification. However, unresolved issues still challenge the guidance of SCD prevention in patients with cardiomyopathies. In this review, we aim to provide an in-depth discussion of the contemporary concepts pertinent to understanding the burden, risk assessment and prevention of SCD in cardiomyopathies (dilated, non-dilated left ventricular, hypertrophic, arrhythmogenic right ventricular, and restrictive). The review first focuses on SCD incidence in cardiomyopathies and then summarizes established and emerging risk factors for life-threatening arrhythmias/SCD. Finally, it discusses validated approaches to the risk assessment and evidence-based measures for SCD prevention in cardiomyopathies, pointing to the gaps in evidence and areas of uncertainties that merit future clarification.

Mortality, Outcomes, Costs, and Use of Medicines Following a First Heart Failure Hospitalization: EVOLUTION HF.

BACKGROUND: There are few contemporary data on outcomes, costs, and treatment following a hospitalization for heart failure (hHF) in epidemiologically representative cohorts. OBJECTIVES: This study sought to describe rehospitalizations, hospitalization costs, use of guideline-directed medical therapy (GDMT) (renin-angiotensin system inhibitors, sacubitril/valsartan, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors), and mortality after hHF. METHODS: 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, longitudinal cohort study using data from electronic health records or claims data sources in Japan, Sweden, the United Kingdom, and the United States. Adults with a first hHF discharge between 2018 and 2022 were included. The 1-year event rates per 100 patient-years (ERs) for death and rehospitalizations (with a primary diagnosis of heart failure (HF), chronic kidney disease [CKD], myocardial infarction, stroke, or peripheral artery disease) were calculated. Hospital health care costs were cumulatively summarized. Cumulative GDMT use was assessed using Kaplan-Meier estimates. RESULTS: Of 263,525 patients, 28% died within the first year post-hHF (ER: 28.4 [95% CI: 27.0-29.9]). Rehospitalizations were mainly driven by HF (ER: 13.6 [95% CI: 9.8-17.4]) and CKD (ER: 4.5 [95% CI: 3.6-5.3]), whereas the ERs for myocardial infarction, stroke, and peripheral artery disease were lower. Health care costs were predominantly driven by HF and CKD. Between 2020 and 2022, use of renin-angiotensin system inhibitors, sacubitril/valsartan, beta-blockers, and mineralocorticoid receptor antagonists changed little, whereas uptake of sodium-glucose cotransporter-2 inhibitors increased 2- to 7-fold. CONCLUSIONS: Incident post-hHF rehospitalization risks and costs were high, and GDMT use changed little in the year following discharge, highlighting the need to consider earlier and greater implementation of GDMT to manage risks and reduce costs.

Worsening of chronic heart failure: definition, epidemiology, management and prevention. A clinical consensus statement by the Heart Failure Association of the European Society of Cardiology.

Episodes of worsening symptoms and signs characterize the clinical course of patients with chronic heart failure (HF). These events are associated with poorer quality of life, increased risks of hospitalization and death and are a major burden on healthcare resources. They usually require diuretic therapy, either administered intravenously or by escalation of oral doses or with combinations of different diuretic classes. Additional treatments may also have a major role, including initiation of guideline-recommended medical therapy (GRMT). Hospital admission is often necessary but treatment in the emergency service or in outpatient clinics or by primary care physicians has become increasingly used. Prevention of first and recurring episodes of worsening HF is an essential component of HF treatment and this may be achieved through early and rapid administration of GRMT. The aim of the present clinical consensus statement by the Heart Failure Association of the European Society of Cardiology is to provide an update on the definition, clinical characteristics, management and prevention of worsening HF in clinical practice.

Impact analysis of heart failure across European countries: an ESC-HFA position paper.

Heart failure (HF) is a long-term clinical syndrome, with increasing prevalence and considerable healthcare costs that are further expected to increase dramatically. Despite significant advances in therapy and prevention, mortality and morbidity remain high and quality of life poor. Epidemiological data, that is, prevalence, incidence, mortality, and morbidity, show geographical variations across the European countries, depending on differences in aetiology, clinical characteristics, and treatment. However, data on the prevalence of the disease are scarce, as are those on quality of life. For these reasons, the ESC-HFA has developed a position paper to comprehensively assess our understanding of the burden of HF in Europe, in order to guide future policies for this syndrome. This manuscript will discuss the available epidemiological data on HF prevalence, outcomes, and human costs-in terms of quality of life-in European countries.

The Heart Failure Association Atlas: Heart Failure Epidemiology and Management Statistics 2019.

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.

Sex Differences in Heart Failure.

Heart failure (HF) represents a global pandemic health problem with a high impact on health-care costs, affecting about 26 million adults worldwide. The overall HF prevalence and incidence are ~2% and ~0.2% per year, respectively, in Western countries, with half of the HF population with reduced ejection fraction (HFpEF) and half with preserved (HFpEF) or mid-range ejection fraction (HFmrEF). Sex differences may exist in HF. More males have HFrEF or HFmrEF and an ischemic etiology, whereas more females have HFpEF and hypertension, diastolic dysfunction, and valvular pathologies as HF etiologies. Females are generally older, have a higher EF, higher frequency of HF-related symptoms, and lower NYHA functional status. Generally, it is observed that female HF patients tend to have more comorbidities such as atrial fibrillation, diabetes, hypertension, anemia, iron deficiency, renal disease, arthritis, frailty, depression, and thyroid abnormalities. However, overall, females have better prognosis in terms of mortality and hospitalization risk compared with men, regardless of EF. Potential sex differences in HF characteristics may be underestimated because of the underrepresentation of females in cardiovascular research and, in particular, the sex imbalance in clinical trial enrollment may avoid to identify sex-specific differences in treatments' benefit.

Nuclear assessment of right ventricle.

For many years, the right ventricle (RV) has been considered a passive chamber with a relatively insignificant role in the overall functionality of the heart. More recently, the role of performance of RV in the clinical presentation and long-term prognosis of multiple pathological states, such as congenital heart diseases, chronic heart failure, pulmonary hypertension, and chronic obstructive pulmonary disease. Despite echocardiography and cardiac magnetic resonance are the 2 most commonly used imaging techniques for noninvasive assessment of RV, nuclear imaging provides new opportunities for comprehensive evaluation of RV from a single study, because it can assess right ventricular perfusion and metabolism as well as morphology and ejection fraction. In this review, we summarize the application of radionuclide techniques (nuclear cardiology) for evaluation of the RV, focusing on its emerging role in the assessment of right ventricular perfusion and metabolism.

Benefits of statins in elderly subjects without established cardiovascular disease: a meta-analysis.

OBJECTIVES: The purpose of this paper was to assess whether statins reduce all-cause mortality and cardiovascular (CV) events in elderly people without established CV disease. BACKGROUND: Because of population aging, prevention of CV disease in the elderly is relevant. In elderly patients with previous CV events, the use of statins is recommended by guidelines, whereas the benefits of these drugs in elderly subjects without previous CV events are still debated. METHODS: Randomized trials comparing statins versus placebo and reporting all-cause and CV mortality, myocardial infarction (MI), stroke, and new cancer onset in elderly subjects (age ≥ 65 years) without established CV disease were included. RESULTS: Eight trials enrolling 24,674 subjects (42.7% females; mean age 73.0 ± 2.9 years; mean follow up 3.5 ± 1.5 years) were included in analyses. Statins, compared with placebo, significantly reduced the risk of MI by 39.4% (relative risk [RR]: 0.606 [95% confidence interval (CI): 0.434 to 0.847]; p = 0.003) and the risk of stroke by 23.8% (RR: 0.762 [95% CI: 0.626 to 0.926]; p = 0.006). In contrast, the risk of all-cause death (RR: 0.941 [95% CI: 0.856 to 1.035]; p = 0.210) and of CV death (RR: 0.907 [95% CI: 0.686 to 1.199]; p = 0.493) were not significantly reduced. New cancer onset did not differ between statin- and placebo-treated subjects (RR: 0.989 [95% CI: 0.851 to 1.151]; p = 0.890). CONCLUSIONS: In elderly subjects at high CV risk without established CV disease, statins significantly reduce the incidence of MI and stroke, but do not significantly prolong survival in the short-term.

Cardiac magnetic resonance for the assessment of myocardial viability: from pathophysiology to clinical practice.

Cardiac magnetic resonance (CMR) is commonly applied for the assessment of myocardial viability in patients with ischemic ventricular dysfunction, and it holds potential advantages over more traditional imaging modalities, including single-photon emission computed tomography (SPECT) and dobutamine stress echocardiography (DSE). CMR-based techniques for viability assessment include the evaluation of transmural extent of the scar using late gadolinium enhancement (LGE) images, the evaluation of end-diastolic wall thickness from resting cine images and the study of inotropic reserve during low-dose dobutamine infusion. During the past decade, the diffusion of the use of CMR for viability assessment confirmed the clinical strengths of this modality and, at the same time, helped to use old techniques with an increased level of awareness. With LGE CMR, both viable and nonviable dysfunctional myocardium can be visualized in a single image, allowing a direct quantification of the amount of regional viability, with a significant impact on the estimation of chance for recovery. As well, studies with CMR applied in the setting of ischemic heart disease allowed a better understanding of the best way to apply and interpret other tests for viability evaluation. For instance, it has been demonstrated that the transmural extension of the scar may influence the level of concordance between SPECT and DSE in assessing myocardial viability. The transmural extent of scar on LGE CMR also correlates with the timing of postrevascularization recovery of systolic function, with significant impact on the diagnostic accuracy of any applied imaging modality.

Assessment of cardiac sympathetic activity by MIBG imaging in patients with heart failure: a clinical appraisal.

Cardiac sympathetic activity can be assessed by (123)I-labelled meta-iodobenzylguanidine (MIBG) scintigraphy. Abnormalities of sympathetic cardiac activity have been shown in patients with heart failure, resulting in reduced MIBG uptake. Abnormal MIBG uptake predicts cardiac death, arrhythmias and all-cause mortality in patients with heart failure with a prognostic power incremental to that of conventional risk markers, and may identify patients at low risk of arrhythmias despite current guideline indications for implantable cardioverter defibrillator or patients at high risk for arrhythmias not fulfilling implantable cardioverter defibrillator indications. Prospective outcome studies are needed to assess whether MIBG imaging will have an impact on the mortality and morbidity of patients with heart failure.