The last released European guidelines on the management of heart failure (HF) recommend in patients with chronic HF with reduced ejection fraction (HFrEF) a pharmacological approach based on four fundamental drugs to be rapidly implemented and then uptitrated to modify disease progression. The aim of the Optimization of Therapy in the Italian Management of Heart Failure (OPTIMA-HF) registry is to collect data on chronic HF outpatients in different settings of care. In the present analysis, we report the first analysis of the OPTIMA-HF registry, focusing on the real-life use of guideline-directed medical therapy in patients affected by HFrEF.

OPTIMA-HF is an observational, cross-sectional, multicentre, real-life Italian registry conducted in two different clinical settings: HF outpatients' clinics of Italian hospitals and community HF outpatients' services. The study comprises a T0 phase-retrospective data collection, in which data of consecutive HF outpatients seen between January and October 2022 were collected; an educational activity phase; and a T1 phase-prospective data collection, in which data of consecutive HF outpatients seen between September 2023 and November 2023 were collected. In the present analysis, we describe the T0 phase focusing on HFrEF drug prescription rates, types, doses, combination therapy, the presence of contraindications and reasons of non-optimized treatment.

Twenty-nine centres enrolled 2110 HF patients, of which 1390 (65.9%) had HFrEF [69.5 ± 11.9 years, 76.2% males, 4.1 years since HF diagnosis, median ejection fraction (EF) 33%]. Among HFrEF patients, 89.1% were on treatment with renin-angiotensin-aldosterone system inhibitor (RAASi)/angiotensin receptor neprilysin inhibitor (ARNI) (72% ARNI and 17.1% RAASi), 95.1% with beta-blockers, 75.8% with mineralocorticoid receptor antagonists (MRA) and 63.2% with sodium/glucose cotransporter 2 inhibitors (SGLT2i). Despite high prescription rates, a non-negligible number of patients with no contraindications were not treated with each specific drug. Patients taking all four drug classes, as recommended by guidelines, were mere 46.9%. Regarding doses, a still low number of patients on RAASi/ARNI and beta-blockers were treated with a dose ≥50% of the target doses recommended by the European guidelines.

The OPTIMA-HF registry reported that HFrEF fundamental drugs are prescribed in most Italian patients; however, <50% of patients receive optimal combination therapy, and still not a satisfying number of patients receive target doses. Strategies to improve implementation of guideline-directed medical therapy are needed to improve HF prognosis.

Pediatric heart failure (HF) research remains in its infancy partly due to the lack of neonatal rat/mouse models of HF. The aim of the study is to introduce a neonatal rat/mouse model of right ventricular (RV) pressure overload (RVPO), a significant cause of pediatric HF, and to uncover the molecular features of RVPO-induced RV hypertrophy and fibrosis-the two most important transitional pathological states between normal and dysfunctional RV. Neonatal rat/mouse model of RVPO was established by pulmonary artery banding (PAB) surgery on postnatal day 1(P1) and confirmed by echocardiography and morphological examination on P7. Bulk RNA and single-cell RNA sequencing was performed on RV tissues, along with bulk RNA sequencing on RV cardiomyocytes, to screen a range of key genes and signaling pathways that are upregulated and that play critical roles in adult hypertrophy and fibrosis. The sequencing results were further verified by qRT-PCR and histological staining. Most of the pathways and associated genes, such as oxidative stress, inflammation, phosphodiesterase, proteasome, protein kinase, transforming growth factor, and angiotensin were not changed or downregulated in the neonatal RVPO model. This study reveals the unique features of hypertrophy and fibrosis in the neonatal RV in response to pressure overload, which partly explains why adult-effective anti-HF drugs fail to treat pediatric HF. More importantly, single-cell RNA sequencing data of the neonatal RV with pressure overload were documented, providing an important reference for future basic or clinical investigations on pediatric RV failure.

The management of complex congenital heart disease has advanced over the years. While certain complex congenital heart diseases are not compatible with life, palliative surgeries have developed to allow these children to survive into adulthood. Consequently, there are more children surviving into adulthood who have previously undergone complex palliative surgeries and have complex anatomy and physiology. There is a high prevalence of heart failure in adults with complex congenital heart disease due to its progressive nature. Often, anatomical and physiological sequelae of the disease itself or its surgical palliation lead to heart failure signs and symptoms over time. The nature of heart failure in this population is different than that of normal adults, and so management strategies must be adjusted based on the unique anatomy and physiology of these patients. While there are guidelines for monitoring and managing adults with complex congenital heart disease, there are limited data for medical therapies that improve symptom burden and mortality. Once these patients have worsening or decompensated heart failure, they often must be considered for advanced therapies, mechanical circulatory support, and transplant. There is still a need for further research and highly powered trials to elucidate how to optimally treat heart failure in adults with complex congenital heart disease.

Acute kidney injury (AKI) is common in hospitalized adults and a risk factor for chronic kidney disease and mortality. The effect of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) post-AKI on mortality and long-term kidney function remains unclear.

Propensity-weighted retrospective observational cohort study.

A total of 3,289 patients with AKI admitted to a tertiary care hospital from November 2015-October 2016, with follow-up until September 2020.

ACEi/ARB use within 180 days post-AKI.

All-cause mortality, and major adverse kidney events (MAKE) as defined by composite of renal replacement therapy post-AKI, sustained estimated glomerular filtration rate (eGFR) decline >30% from baseline, or eGFR ≤15 mL/min/1.73 m2.

We generated propensity weights for ACEi/ARB use post-AKI, using age, sex, comorbid conditions, prior medication, intensive care unit admission, severe sepsis, and index AKI Kidney Disease: Improving Global Outcomes severity. Cox proportional hazard models were used to test associations of post-AKI ACEi/ARB with mortality, MAKE, and joint models for eGFR slopes.

A total of 2,309 (70.2%) participants died or experienced MAKE by end of follow-up. 161 (4.9%) and 406 (12.3%) patients initiated or resumed prior ACEi/ARB use within 180 days post-AKI, respectively. Although the overall cohort had no significant mortality association with post-AKI ACEi/ARB use, a significant association with lower mortality was observed in patients with KDIGO 3 AKI (HR, 0.40; 95% CI, 0.21-0.75; P interaction = 0.003). However, post-AKI ACEi/ARB use was associated with increased MAKE in patients without cardiovascular indications for ACEi/ARB use (HR, 1.52; 95% CI, 1.17-1.98; P interaction = 0.03). Although post-AKI use of ACEi/ARB was associated with acute eGFR decline (initial eGFR change -2.3 mL/min/1.73 m2/year; 95% CI, -3.1 to -1.5; P < 0.001), no association with longer-term eGFR decline was observed.

Retrospective observational study on heterogeneous AKI cohort without data on ACEi/ARB cumulative exposure.

Early ACEi/ARB post-AKI was not associated with better long-term survival or kidney function but was associated with lower mortality in patients with KDIGO 3 AKI.

For many years, pharmaceutical expenditure has been the second largest cost item for statutory health insurance funds (SHI) in Germany after hospital costs. Since prescriptions and expenditure on medicines play such a major role in the German healthcare system, the question arises as to what causes changes in prescriptions. To answer this question, the prescribing trends for the top 10 drugs in 2022 were analyzed over a period of 38 years, from 1985 to 2022. The prescribed defined daily doses (DDD) and the costs per defined daily dose for the 10 medicines were taken from the Arzneiverordnungsreport (AVR) from 1986 to 2023, and the changes in prescribing behavior and their causes were analyzed. The ten most important medicines in 2022, accounting for over 41% of all prescribed daily doses, were ramipril, candesartan, pantoprazole, amlodipine, atorvastatin, levothyroxine, torasemide, simvastatin, bisoprolol, and metoprolol. There are many different reasons for an increase in prescriptions, such as the introduction of generics, a positive study, or a price reduction. Further reasons for an increase in prescriptions are an extension of the indication or the recall of a competing medicine. A change in guidelines or the increasing treatment of laboratory values without clinical symptoms can also lead to an increase in prescriptions. There are also many different reasons for a drop in prescriptions, such as the generic launch of a competitor medicine or a positive study for a competitor medicine. Other reasons for a drop in prescriptions are a negative study or a discussion about the use of a drug. Sometimes, the reasons for prescription changes are also irrational. Overall, this is the most comprehensive long-term analysis of drug prescriptions in Germany. Our data is helpful for predicting drug prescriptions and for preventing future drug shortages not only in Germany but also worldwide.

This clinical consensus statement revisits the role of left ventricular ejection fraction (LVEF) as a measurement of cardiac function, a prognostic marker and a major criterion to classify patients with heart failure, and gives new advice for clinical practice. Heart failure is traditionally classified on the basis of LVEF thresholds and this has major implications for treatment recommendations. However, the reproducibility of LVEF measurement is poor and its prognostic and diagnostic value lessens when it is above 45%, with no relationship with the severity of either cardiac dysfunction or outcomes at higher values. These limitations dictate the need for a more comprehensive approach to classify and assess heart failure focusing more on the trajectory of LVEF rather than to its absolute value. Furthermore, the assessment of LVEF is not required for the initiation of treatments like sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists and diuretics in patients with suspected de novo heart failure and elevated N-terminal pro-B-type natriuretic peptide levels. Future research utilizing advanced imaging techniques and biomarkers which can better characterize myocardial structure, metabolism and performance may facilitate the identification of alternative therapeutic targets and better ways to monitor heart failure therapies across the entire spectrum of LVEF.

The optimal timing for prescribing guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF) during acute decompensated heart failure (ADHF) remains uncertain. This study evaluated the real-world impact of early in-hospital quadruple GDMT prescription in ADHF patients with HFrEF.

In this retrospective cohort study using the Institutional aCute descompensAted heaRt failUre regiStry (ICARUS), we analysed 2051 HFrEF patients (71% male, median age 68 years) hospitalized for ADHF between June 2022 and March 2024. Early quadruple therapy was defined as the prescription of beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs)/angiotensin receptor-neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists (MRAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) within 48 h of admission. Among included patients, 898 (43.8%) received early quadruple therapy. Using optimal full matching propensity score methodology, early quadruple therapy was associated with lower 30 day mortality/rehospitalization [relative risk (RR) 0.73; 95% confidence interval (CI) 0.55-0.97, P = 0.028], reduced in-hospital mortality (RR 0.29; 95% CI 0.15-0.56, P < 0.001) and shorter hospital stay (β = -2.65 days; 95% CI -3.67 to -1.63, P < 0.001). Patients receiving early quadruple therapy showed higher rates of GDMT continuation at discharge (RR 3.82; 95% CI 3.01-4.86, P < 0.001).

In this HFrEF cohort, early initiation of comprehensive GDMT during ADHF hospitalization was associated with improved clinical outcomes. Future randomized trials including patients across the full spectrum of ejection fraction are needed to validate these findings and determine their applicability to other heart failure phenotypes.

This clinical consensus statement revisits the role of left ventricular ejection fraction (LVEF) as a measurement of cardiac function, a prognostic marker and a major criterion to classify patients with heart failure, and gives new advice for clinical practice. Heart failure is traditionally classified on the basis of LVEF thresholds and this has major implications for treatment recommendations. However, the reproducibility of LVEF measurement is poor and its prognostic and diagnostic value lessens when it is above 45%, with no relationship with the severity of either cardiac dysfunction or outcomes at higher values. These limitations dictate the need for a more comprehensive approach to classify and assess heart failure focusing more on the trajectory of LVEF rather than to its absolute value. Furthermore, the assessment of LVEF is not required for the initiation of treatments like sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists and diuretics in patients with suspected de novo heart failure and elevated N-terminal pro-B-type natriuretic peptide levels. Future research utilizing advanced imaging techniques and biomarkers which can better characterize myocardial structure, metabolism and performance may facilitate the identification of alternative therapeutic targets and better ways to monitor heart failure therapies across the entire spectrum of LVEF.

Chagas disease is a major health issue in Latin America and is now spreading globally because of migration. Chronic Chagasic cardiomyopathy (CCC) leads to heart failure with a reduced ejection fraction (HFrEF). Left ventricular reverse remodeling (LVRR), defined as an improved LVEF, is associated with improved outcomes in patients with other HFrEF etiologies. Therefore, we evaluated the relationship between LVRR and survival in CCC patients with an LVEF<40%.

This retrospective, single-center study included patients diagnosed with CCC and LVEF<40% between January 2006 and September 2021. Patients were divided into two groups: positive RR (PRR; LVEF≥40% or an absolute LVEF increase of ≥ 10%) and negative RR (NRR). Propensity score matching (PSM) was used to account for baseline differences, and Cox proportional hazards models were applied to determine independent predictors of mortality and heart transplantation.

A total of 1,043 patients were evaluated; 221 (21.2%) were classified as having PRR, and 822 (78.8%) were classified as having NRR. PRR status was associated with a 55% lower risk of all-cause mortality and heart transplantation over 15 years (p = 0.002). Multivariate Cox analysis revealed that predictors of total mortality and heart transplantation included NRR status, a worse NYHA class, lower serum sodium levels, larger LV dimensions, and moderate-to-severe tricuspid regurgitation (TR). The PRR predictors were smaller LV dimensions, less mitral regurgitation, and the absence of triple therapy at baseline. NRR patients were more likely to be on triple therapy at baseline.

PRR improves survival in CCC patients with HFrEF. Identifying patients with potential for LVRR, alongside early therapeutic interventions, may reduce mortality in this population. Future research should focus on therapies that promote LVRR in patients with CCC.

Cardiac remodelling is a key determinant of worse cardiovascular outcome in patients with heart failure (HF) and reduced ejection fraction (HFrEF). It affects both the left ventricle (LV) structure and function as well as the left atrium (LA) and the right ventricle (RV). Guideline recommended medical therapy for HF, including angiotensin-converting enzyme inhibitors/angiotensin receptors II blockers/angiotensin receptor blocker-neprilysin inhibitors (ACE-I/ARB/ARNI), beta-blockers, mineralocorticoid receptor antagonists (MRA) and sodium-glucose transport protein 2 inhibitors (SGLT2i), have shown to improve morbidity and mortality in patients with HFrEF. By targeting multiple pathophysiological pathways, foundational HF therapies are supposed to drive their beneficial clinical effects by a direct myocardial effect. Simultaneous initiation of guideline directed medical therapy (GDMT) through a synergistic effect promotes a 'reverse remodelling', leading to a full or partial recovered structure and function by enhancing systemic neurohumoral regulation and energy metabolism, reducing cardiomyocyte apoptosis, lowering oxidative stress and inflammation and adverse extracellular matrix deposition. The aim of this review is to describe how these classes of drugs can drive reverse remodelling in the LV, LA and RV and improve prognosis in patients with HFrEF.

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide. While pharmacological therapy is foundational, lifestyle modifications are increasingly recognised for their complementary role. This narrative review explores the synergistic effects of lifestyle interventions, combined with pharmacological treatment, in HF management. A literature search (2000-2025) was conducted using PubMed, Scopus, Cochrane, and Google Scholar, to identify studies on integrative approaches to HF care. Lifestyle changes, such as dietary modification, exercise, weight management, smoking and alcohol cessation, and psychosocial support, enhance the efficacy of standard therapies, improve quality of life, and reduce hospitalisations. Integration with medications, like renin-angiotensin-aldosterone system (RAAS) inhibitors, beta-blockers, and sodium-glucose cotransporter-2 (SGLT2) inhibitors, shows improved neurohormonal balance, reduced inflammation, better endothelial function, and delayed cardiac remodelling. However, socioeconomic and cultural barriers challenge real-world implementation. Combining lifestyle interventions with pharmacotherapy provides a holistic, patient-centred strategy for HF management. Future efforts should focus on personalised care, multidisciplinary teams, and policy support, to improve adherence and outcomes.

The goals of this retrospective cohort analysis were to determine real-world dose and titration patterns of sacubitril/valsartan (SAC/VAL), a heart failure medication, and examine whether dose patterns are associated with healthcare utilization and costs.

Adult health plan members (18-100 years old) who initiated SAC/VAL between 2020 and 2022 and had continuous enrollment 6 months prior to, and at least 3 months following SAC/VAL initiation were identified. Members also had to have 3 months of SAC/VAL fills with good adherence (N =  2,977). Claims data were used to characterize dosage patterns and compare total costs of care, as well as all-cause and heart failure- hospital admissions across those with different terminal SAC/VAL doses.

Most members initiated SAC/VAL at the lowest dose (76%, n =  2,267), of whom few titrated upward by their final fill (31%, n =  703). Overall, only 19% (n =  563) were at target by their final fill. Those ending on higher doses experienced significantly fewer all-cause admissions (incidence rate ratios of 1.52 [SE = .16] to 2.66 [SE = .37]; ps < .001) and incurred significantly lower total costs of care while on SAC/VAL (cost ratios of 1.21 [SE = .06] to 1.48 [SE = .09]; ps < .001).

Most individuals initiate and remain on the lowest SAC/VAL dose despite guidelines to titrate upward. SAC/VAL dosage is significantly associated with outcomes, with higher doses associated with more clinical and cost benefits. Research is needed to identify barriers to dose titration and to develop interventions for maximal patient benefit.

Heart failure (HF) is a clinical syndrome with high incidence and prevalence and high morbidity and death rate, even in the short term, representing a serious public health issue, mainly in older people. It is a growing cause for hospital admission in this age group, being frequently associated with several comorbidities, further aggravating the disease's course. Moreover, older HF patients are usually affected by clinical conditions, like frailty, malnutrition, and cachexia, which significantly impact the overall management of HF and need to be properly identified and treated. Diagnosing and managing HF in older patients may be very complicated and challenging. Although specific data on treatment of both acute and chronic HF in older subjects are limited and mainly extrapolated from large-scale clinical trials, the standard pharmacological management may be considered well-tolerated and generally safe. In any case, a personalized and tailored approach is mandatory and is based on severity of comorbidities, overall status, and prognosis, above all in frailer and more comorbid subjects, due to the higher rate of drug interactions, side effects, and therapy discontinuation in this population. In this scenario, palliative care has become a fundamental part of HF management in the elderly in order to improve their care and the quality of life. Moreover, an increasing number of promising pharmacological options deserve further investigation in order to support clinicians in optimizing management of comorbid and frailer patients. In this work, we provide detailed and updated insight into clinical, therapeutic, and prognostic features of both acute and chronic HF in the older population.

Sacubitril/valsartan (SAV) is crucial for managing heart failure (HF). Randomized clinical trials have shown SAV's superiority over angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) in reducing N-terminal pro-B-type natriuretic peptide levels. However, results for cardiovascular (CV) mortality, HF rehospitalization, and all-cause mortality have been mixed.

This study aimed to determine hard endpoints among the population with HF treated with SAV vs ACEI/ARBs and conduct a comprehensive risk-benefit analysis of the safety profile for SAV vs ACEI/ARB.

We queried PubMed, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials for randomized clinical trials from inception to November 2023. We included studies that compared SAV to ACEI or ARBs and reported hard endpoints, including all-cause mortality, CV mortality, and HF rehospitalizations. Random effect model was used, and categorical values were analyzed using risk ratios (RRs) and 95% CI. The I2 test was used to assess between-study heterogeneity. Publication bias was assessed via funnel plots and the Egger test. This study was registered in PROSPERO (CRD42024497661).

The study included a total of 14 trials (n = 25,167). SAV reduced all-cause mortality in the population with an ejection fraction (EF) ≤40% (RR: 0.88; 95% CI: 0.81-0.94; P = 0.0006), but not in those with EF >40% (RR: 0.97; 95% 0.85-1.11; P = 0.67). There was no difference in CV mortality across EF spectrums (RR: 0.9; 95% CI: 0.79-1.03; P = 0.13). HF readmission was lower in the SAV-treated group regardless of EF (RR: 0.85; 95% CI: 0.79-0.91; P = 0.00001).

The SAV-treated group, across all EF spectrum, was less likely to be rehospitalized than the ACEI/ARB-treated group. However, all-cause mortality reduction was only noted in the SAV group with EF <40%. No reduction in CV-related mortality was observed across the EF spectrum.

End-stage heart failure (HF) accounts for 1% to 10% of all HF cases. It is frequently associated with coexistent atrial fibrillation due in part to structural changes related to altered hemodynamics, increased wall stress, and neurohormonal activation. The treatment remains challenging because of frequent atrial remodeling, comorbidities, and high recurrence rates. Studies have found no benefit of medical rhythm control compared with rate control. However, recent data suggest that catheter ablation might be associated with a reduction in HF symptomatology and all-cause mortality. Alternative treatment options including AV nodal ablation are available for refractory cases, but should not delay urgent heart transplantation.

Recently, usage of the term 'heart failure with preserved ejection fraction (HFpEF)' has predominated over the term 'diastolic heart failure (DHF).' The term 'preserved ejection fraction' represents only one aspect of DHF and does not provide insight into the hemodynamic mechanism of heart failure. In heart failure with reduced ejection fraction (HFrEF), depressed ejection fraction is the independent determinant of prognosis regardless of etiology. However, in HFpEF, because the prognosis is predominantly determined by etiologies of HFpEF, results of the drug on the prognosis in the clinical trial cannot be interpreted as it is. Therefore, studies on patients with HFpEF should be restricted to patients with diastolic dysfunction and, effects of drugs should be focused on symptom improvement not survival benefit. One reason for the prevalent use of HFpEF over DHF is the complexity in assessing diastolic function. Current official recommendations for the evaluation of diastolic function are too complex to be widely applied in the patient enrollment in large clinical trials as well as not easily applicable in our daily clinical practice. Therefore, there is a clinical need for a simple and practical way of assessing diastolic function.

Sacubitril/Valsartan is a combination of neprilysin inhibitor and angiotensin II receptor blocker that proved its own efficacy and safety in heart failure patients to ameliorate cardiovascular morbidity and mortality compared to angiotensin II-converting enzyme inhibitors alone. However, end-stage renal disease patients have not been included in the randomized controlled trials, so the beneficial effects as well as the risk profile of this association remain still undefined in these patients. Only observational studies on this drug association have been carried out in end-stage renal disease patients investigating mostly biohumoral or echocardiographic markers. Therefore, its application is still controversial and not free of complications due to the potential risk of hypotension and hyperkaliemia. The efficacy to improve biohumoral markers and cardiac function in dialysis patients and the potential application especially in those patients with severe and resistant hypertension and/or left ventricular dysfunction could be crucial in end-stage renal disease patients. Ongoing long-term randomized controlled trials should thoroughly define the effective benefits and/or adverse effects in patients on substitutive treatment.

Renin-angiotensin-aldosterone system inhibitors (RAASi) are widely used in treatment of cardiovascular and renal disease. While effective, they pose a risk of hyperkalemia. In the general population, risk factors for hyperkalemia include chronic kidney disease, congestive heart failure, and use of medication affecting potassium balance. These risk factors are prevalent in frail older patients. Therefore, this study aims to explore the prevalence and risk factors for hyperkalemia associated with RAASi use in this vulnerable population.

This single-center, cross-sectional study included RAASi users aged ≥ 70 years who presented at the emergency department. Clinical Frailty Scale (CFS) according to Rockwood was calculated retrospectively from information in clinical files. All patients with CFS ≥ 5 were considered frail. Hyperkalemia was defined as serum potassium ≥ 5.5 mmol/L at time of presentation at the emergency department. Potential risk factors for hyperkalemia in older patients were identified using logistic regression models.

Of the 2023 participants, 86 (4.3%) were hyperkalemic, with no significant difference between frail and non-frail patients (4.7% versus 3.3%, p-value 0.157). Hyperkalemic patients were slightly younger than non-hyperkalemic patients (median age 83 versus 84 years, p-value 0.023), and females were slightly overrepresented in both groups (52.6% and 53.5%, p = 0.867). Risk factors associated with hyperkalemia in older RAASi users included younger age (odds ratio (OR) 0.95, 95% confidence intervals (CI) 0.92-0.99, p = 0.010), diabetes mellitus (OR 1.67, 95% CI 1.05-2.65, p = 0.030), moderate to severe kidney failure (OR 9.87, 95% CI 6.01-16.21, p < 0.001), and use of potassium-binding agents (OR 14.62, 95% CI 1.56-137.40, p = 0.019) and potassium-sparing diuretics (OR 2.66, 95% CI 1.57-4.50, p < 0.001).

Contrary to expectations, this study found no association between frailty and hyperkalemia in older RAASi users visiting the emergency department. These results suggest that frail older patients without additional risk factors can be treated with RAASi when indicated, similar to the general population. The main risk factors for hyperkalemia in this population remain consistent with those in the general population, emphasizing the importance of monitoring kidney function and medication use.

Data from pivotal randomized controlled trials established the four pillars of guideline-directed medical therapy in heart failure with reduced ejection fraction. The randomized controlled trials enrolled stable patients with New York Heart Association functional class II-III and a low incidence of cardiovascular death and hospitalization for heart failure. Whether the four pillars retain therapeutic value when a patient's symptoms worsen and life expectancy decreases has received scarce attention. We review the observational studies that point to the fading benefit of neurohormonal modulation and cardiac afterload reduction in the late stages of cardiovascular or renal diseases. We then propose a pragmatic approach for collecting evidence-based data on sequential withdrawal of the four pillars in patients with heart failure and reduced ejection fraction after years of guideline-directed medical therapy.

Coronary artery disease is the leading cause of acute and chronic heart failure. Patients with heart failure and ischemic heart disease need a tailored assessment to define the appropriate treatment, while a specific multidisciplinary management plan should be followed. Indeed, several factors should be assessed before starting treatment, such as heart failure symptoms and/or signs, angina, electrocardiographic features, right and left ventricular systolic and diastolic function, serological abnormalities, cardiac structural and functional integrity, and pulmonary function. New scenarios and developments have emerged recently in this field, increasing our knowledge regarding pathophysiology, exercise, and pharmacology. Effective and appropriate management and treatment reduce the risk of death and hospitalization for heart failure. Herein, we provide an updated, state-of-the-art overview of pharmacological treatment and cardiac rehabilitation in patients with chronic heart failure and coronary artery disease. Furthermore, tailored and contemporary management in clinical practice will be proposed for this specific and fragile patient population.

Background: The prognosis of acute decompensated heart failure (ADHF) and heart failure (HF) with atrial fibrillation (AF) has been dismal. This study was performed to investigate the clinical outcomes of catheter ablation (CA) performed in patients with concurrent ADHF and AF. Methods: We retrospectively analyzed ADHF patients with AF who were admitted to our institution from 2007 to 2017. Results: In total, 472 patients were included in this study, with a mean follow-up duration of 32.8 ± 32.9 months. The 5-year event-free rate (cardiovascular death and HF hospitalization) was 61.4%, and the 10-year event-free rate was 42.7%. A comparative analysis of the event group and control group revealed that patients in the event group were older (event group vs. control group: 72.1 ± 11.0 vs. 68.8 ± 13.4 years, p = 0.008) and had a higher proportion of Clinical Scenario 3 classifications (event group vs. control group: 24% vs. 12%, p = 0.001). Notably, patients in the event group had a lower sinus rhythm maintenance rate (event group vs. control group: 17% vs. 31%, p < 0.001) and CA rate (event group vs. control group: 9% vs. 21%, p = 0.003). The CA group had a higher event-free rate than the non-CA group, and this trend persisted even after matching the patients' backgrounds (log-rank test: p < 0.001). Conclusions: Patients presenting with AF at the onset of ADHF showed a poor prognosis, whereas CA demonstrated potential for improving the prognosis for some of these patients.

Implantable cardioverter-defibrillators (ICDs) are recommended to reduce the risk of sudden cardiac death (SCD) in patients with heart failure with reduced ejection fraction (HFrEF). The landmark studies leading to the current guideline recommendations preceded the 4 pillars of guideline-directed medical therapies (GDMTs). Therefore, some have questioned the role of ICDs for primary prevention in current clinical practice. In this paper, the authors provide an overview of the current ICD recommendations, including the instrumental clinical trials, the risk of SCD as observed in clinical trials vs real-world scenarios, disparities in ICD use among different patient populations, the impact of contemporary GDMT on outcomes, and ongoing and future trials and methodologies to help identify patients who are at an increased risk of SCD and who may benefit from an ICD. The authors also propose a pragmatic guidance for clinicians when they engage in the shared decision-making discussions for primary ICD implantation.

Heart failure (HF) is a common condition and one of the main morbidity and mortality factors in elderly patients. The incidence of HF progressively increases with age, reaching >10% in those aged 70 years or over. In the elderly population, both the diagnosis and the management of HF prove challenging, often requiring specialized care and a multidisciplinary approach. In seniors, atypical presentation of HF is much more common than in younger patients; thus, a holistic assessment with biomarkers related to HF allows for early diagnosis and accurate risk stratification in this group of patients. This article reviews the clinical and diagnostic differences in elderly patients with HF, highlighting the presence of comorbidities, frailty, cognitive impairment, and polypharmacy, as well as discussing potential biomarkers that may have clinical application in this population.

Advanced heart failure primarily manifests during and after hospitalization for decompensation. Identifying prognostic factors is crucial for distinguishing patients who may benefit from drug therapy from those with end-stage disease. This study aimed to evaluate the prognostic significance of systemic vasoconstriction in patients with decompensated heart failure with a reduced ejection fraction. We evaluated patients hospitalized for decompensated heart failure with a left ventricular ejection fraction of < 40% who underwent non-invasive hemodynamic monitoring using the Modelflow method. The primary endpoint was all-cause mortality, and the data were analyzed using logistic regression. This study included 58 patients (71% men) with a mean age of 58.9 years, an ejection fraction of 23.4%, a median B-type natriuretic peptide of 1,005.0 pg/mL (interquartile range = 1,498.0), and 43% with Chagas disease. The cardiac index was 2.7 L∙min-1∙m-2, and the systemic vascular resistance index was 2,403.9 dyn∙s∙cm-5∙m-2. Over an average follow-up of 29.0 months, 51 (87.9%) patients died. Assessing three-year mortality, high systemic vascular resistance indices were predictive of events with a relative risk of 3.9 (95% confidence interval = 1.1-13.9; P-value = 0.037). In conclusion, non-invasive hemodynamic monitoring identifies systemic vasoconstriction, which is associated with poor prognosis in patients with advanced heart failure and reduced ejection fraction.

To clarify the efficacy of mineralocorticoid receptor antagonists (MRA) and renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI) in heart failure with mildly reduced ejection fraction (HFmrEF).

This study assessed the association between these medications and outcomes in HFmrEF using data from the National Taiwan University Hospital-integrated Medical Database. The primary outcome was cardiovascular mortality/heart failure hospitalization (HHF). Inverse probability of treatment weighting balanced baseline patient characteristics. The exposure of primary interest was use of MRA and use of RASI/ARNI, while the non-user group was also likely to receive other heart failure medication treatment.

Among 2,584 HFmrEF patients, 17% received MRA and 43% received RASI/ARNI. Predictors of MRA use included older age, slightly higher ejection fraction, and lower NT-proBNP level. RASI/ARNI use was predicted by higher BMI, lower NT-proBNP level, normal uric acid and potassium levels. MRA use was not associated with a lower risk of cardiovascular death [hazard ratio = 0.89, 95% confidence interval (CI): 0.78-1.02] or HHF (hazard ratio = 1.01, 95% CI: 0.94-1.09). Conversely, RASI//ARNI use was linked to a lower risk of cardiovascular death (hazard ratio = 0.82, 95% CI: 0.71-0.94) but not HHF (hazard ratio = 0.995, 95% CI: 0.924-1.07). Landmark analysis showed no significant difference in outcomes for follow-up durations exceeding 2 years.

MRA had a neutral effect on cardiovascular death and HHF, while RASI/ARNI was associated with a lower risk of cardiovascular death. RASI/ARNI may be more beneficial than MRA for HFmrEF patients. Regular re-evaluation is essential to adjust heart failure treatment.

Systemic sclerosis (SSc) is an autoimmune connective disease characterised by excessive extracellular matrix deposition and widespread skin and internal organ fibrosis including various cardiac manifestations. Heart involvement is one of the leading causes of death among patients with SSc. In this study, we aimed to assess the effect of various vasodilator treatments.

We used data from a national multicentric prospective study using the French SSc national database. We estimated the average treatment effect (ATE) of sildenafil, bosentan, angiotensin-converting enzyme (ACE) inhibitors and iloprost on diastolic dysfunction, altered ejection fraction <50% and pulmonary arterial hypertension (PAH) using a causal method, namely the longitudinal targeted minimum loss-based estimation, to adjust for confounding and informative censoring.

We included 1048 patients with available data regarding treatment. Regarding sildenafil analyses, the ATE on diastolic dysfunction at 3 years was -2.83% (95% CI -4.06; -1.60, p<0.00001), and the estimated ATE on altered ejection fraction <50% was -0.88% (95% CI -1.70; -0.05, p=0.037). We did not find a significative effect on PAH. Regarding bosentan, ACE inhibitors and iloprost, none of them neither showed a significant effect on diastolic dysfunction, altered ejection fraction <50% or PAH.

Using causal methods, our study is the first and largest suggesting that sildenafil might have benefits among SSc patients regarding diastolic dysfunction and altered ejection fraction occurrence. However, further studies assessing the effect of vasodilators on heart-related outcome among SSc patients are needed to confirm those exploratory results.

Despite the exponential growth in telemedicine visits in clinical practice due to the COVID-19 pandemic, it remains unknown if telemedicine visits achieved similar adherence to prescribed medications as in-person office visits for patients with heart failure.

Our study examined the association between telemedicine visits (vs in-person visits) and medication adherence in patients with heart failure.

This was a retrospective cross-sectional study of adult patients with a diagnosis of heart failure or an ejection fraction of ≤40% using data between April 1 and October 1, 2020. This period was used because New York University approved telemedicine visits for both established and new patients by April 1, 2020. The time zero window was between April 1 and October 1, 2020, then each identified patient was monitored for up to 180 days. Medication adherence was measured by the mean proportion of days covered (PDC) within 180 days, and categorized as adherent if the PDC was ≥0.8. Patients were included in the telemedicine exposure group or in-person group if all encounters were video visits or in-person office visits, respectively. Poisson regression and logistic regression models were used for the analyses.

A total of 9521 individuals were included in this analysis (telemedicine visits only: n=830 in-person office visits only: n=8691). Overall, the mean age was 76.7 (SD 12.4) years. Most of the patients were White (n=6996, 73.5%), followed by Black (n=1060, 11.1%) and Asian (n=290, 3%). Over half of the patients were male (n=5383, 56.5%) and over half were married or living with partners (n=4914, 51.6%). Most patients' health insurance was covered by Medicare (n=7163, 75.2%), followed by commercial insurance (n=1687, 17.7%) and Medicaid (n=639, 6.7%). Overall, the average PDC was 0.81 (SD 0.286) and 71.3% (6793/9521) of patients had a PDC≥0.8. There was no significant difference in mean PDC between the telemedicine and in-person office groups (mean 0.794, SD 0.294 vs mean 0.812, SD 0.285) with a rate ratio of 0.99 (95% CI 0.96-1.02; P=.09). Similarly, there was no significant difference in adherence rates between the telemedicine and in-person office groups (573/830, 69% vs 6220/8691, 71.6%), with an odds ratio of 0.94 (95% CI 0.81-1.11; P=.12). The conclusion remained the same after adjusting for covariates (eg, age, sex, race, marriage, language, and insurance).

We found similar rates of medication adherence among patients with heart failure who were being seen via telemedicine or in-person visits. Our findings are important for clinical practice because we provide real-world evidence that telemedicine can be an approach for outpatient visits for patients with heart failure. As telemedicine is more convenient and avoids transportation issues, it may be an alternative way to maintain the same medication adherence as in-person visits for patients with heart failure.

During the 25 years of the existence of the Russian Society of Experts in Heart Failure, it has become the most numerous and authoritative medical association. The Society has representative offices in 52 regions of Russia, and its active members amount to more than 4,000 various specialists. More than 200 Schools, regional conferences, and annual Congresses have been held annually. Dozens of clinical studies have been performed under the auspices of the Society, and the Cardiology journal has been published. This article also outlines the following new promising areas for the development of the Society: widespread introduction of modern clinical guidelines into clinical practice; transition to personalized medicine based on phenotyping of patients with heart failure; acceleration of heart failure diagnostics and earlier initiation of treatment with recommended doses; transition to remote follow-up of heart failure outpatients.

Congenital heart disease (CHD) is the most common global congenital defect affecting over 2.4 million individuals in the United States. Ongoing medical and surgical advancements have improved the survival of children with CHD leading to a shift where, as of 2010, adults constitute two-thirds of the CHD patient population. The increasing number and aging of adult congenital heart disease (ACHD) patients present a clinical challenge due to heightened complexity, morbidity, and mortality. Studies indicate that 1 in 13 ACHD patients will develop heart failure (HF) in their lifetime. ACHD-HF patients experience more frequent emergency department visits, higher hospitalization rates, longer hospital stays, and higher mortality compared to non-ACHD patients with heart failure (non-ACHD-HF). Despite HF being the leading cause of death in ACHD patients, there is a notable gap in evidence regarding treatment. While guideline-directed medical therapy (GDMT) has been extensively studied in non-ACHD-HF, research specific to ACHD-HF individuals is limited. This article aims to comprehensively review available literature addressing the pharmacological treatment of ACHD-HF.

Heart failure (HF) is a global health challenge that requires a multidisciplinary approach. Despite recent advances in pharmacological and interventional therapy, morbidity and mortality in these patients remain high. For this reason, and because of its interplay with other cardiovascular and non-cardiovascular diseases, HF represents a major area of research, with new trials being published every year and international guidelines constantly updated.

The authors review the current status and possible future developments in HF pharmacotherapy.

The treatment of HF has made significant advances in recent years, and the current recommendations are based on large outcome trials. This has led to significant reductions in both mortality and morbidity, but the death rate remains unacceptably high. In this context, a patient-centered approach that considers comorbidities and specific clinical scenarios when dosing HF medication is essential. Prevention of hospital admissions for cardiac decompensation is of utmost importance in patients with HF as is the enablement of activities of daily living, an endpoint which has only recently been incorporated into major HF trials.

Individuals with pacemakers are at increased risk of left ventricular systolic dysfunction (LVSD). Whether screening for and optimizing the medical management of LVSD in these individuals can improve clinical outcomes is unknown. In the present study, in a multicenter controlled trial (OPT-PACE), we randomized 1,201 patients (717 men) with a pacemaker to echocardiography screening or usual care. In the screening arm, LVSD was detected in 201 of 600 (34%) patients, who then received management in either primary care or a specialist heart failure (HF) and devices clinic. The primary outcome of the trial was the difference in a composite of time to first HF hospitalization or death. Over 31 months (interquartile range = 30-40 months), the primary outcome occurred in 106 of 600 (18%) patients receiving echocardiography screening, which was not significantly different compared with the occurrence of the primary outcome in 115 of 601 (19%) patients receiving the usual care (hazard ratio = 0.89; 95% confidence interval = 0.69, 1.17). In a prespecified, nonrandomized, exploratory analysis, patients with LVSD managed by the specialist clinic experienced the primary outcome event less frequently than those managed in primary care. The results of this trial indicate that echocardiography screening commonly identifies LVSD in individuals with pacemakers but alone does not alter outcomes. ClinicalTrials.gov registration: NCT01819662 .

Heart failure is a syndrome that may develop when cardiovascular disease progresses or is insufficiently treated and associated with a poor quality of life, high mortality rates, and increased healthcare expenditures. Prevention and treatment of heart failure are therefore of utmost importance. New therapies in patients with cardiovascular disease have recently been shown to be effective in the prevention and sometimes treatment of heart failure, and additional research is underway. Specifically, in high-risk patients with either (a combination of) diabetes, chronic kidney disease, and/or heart failure, three specific drug classes [sodium-glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP-1-RAs), and non-steroidal mineralocorticoid receptor antagonists (MRAs)] have taken centre stage in therapeutic approach for these high cardiovascular risk patients. The commonality of these drugs is the finding that they improve cardiovascular and renal endpoints across the cardiorenal continuum and SGTL2i have already proved effective in all subtypes of heart failure, while we await data on non-steroidal MRA therapy in heart failure. The story may be different for GLP-1-RA in patients with established heart failure, but these drugs are effective in reducing cardiovascular events in patients with diabetes. Taken together, these new therapies advance the treatment and improve the associated outcomes of patients with cardiorenal disease and diabetes, with similar characteristics and effectiveness in different conditions.