Medical Therapy For Heart Failure Research Articles

Guideline-directed medical therapy for heart failure in arrhythmia-induced cardiomyopathy with improved left ventricular ejection fraction.

No study has analyzed the impact of guideline-directed medical therapy in preventing heart failure (HF) relapse in patients with arrhythmia-induced cardiomyopathy (AiCM) following left ventricular ejection fraction (LVEF) improvement. We analyzed data from a single-center cohort of 200 patients admitted for HF, LVEF <50% and cardiac arrhythmia considered by cardiologists to be the precipitating cause of the episode. The primary endpoint was time-to-HF relapse, defined as the composite of readmission for HF, Emergency Department (ED) visit for HF, or significant decline in LVEF. Changes in medication were recorded and a time-varying multivariate Cox regression was performed. After a median follow-up period of 6.14 years, diagnostic confirmation was achieved in 188 out of the initial 200 patients with suspected AiCM. A total of 89 patients (47.3%) met the primary endpoint. RAS inhibitors (adjusted hazard ratio (HR) 0.50 [0.31-0.81]; p = 0.005) and beta-blockers (adjusted HR 0.48 [0.28-0.81]; p = 0.006) were associated with a lower incidence of relapse. Mineralocorticoid receptor antagonists were associated with a significantly lower incidence of ED visits for HF (adjusted HR 0.38 [0.15-0.95]; p = 0.038), but did not achieve statistical significance for the combined primary endpoint. Antiarrhythmic drugs did not show a significant impact on the primary endpoint. Maintaining RAS inhibitors and beta-blockers was associated with a significantly lower incidence of relapse in the setting of AiCM with improved LVEF.

Anomalous Origin of The Left Coronary Artery from Pulmonary Artery Mimicking Antero-Lateral ST-Elevation Myocardial Infarction – A Case Report

Abstract Background Anomalous origin of the left coronary artery (LCA) from the pulmonary artery (PA) (ALCAPA) is a rare congenital abnormality. We present a case of an ALCAPA in a 25-year-old man. Case summary A 25-year-old male with no past medical history was admitted to our intensive cardiac care unit (ICCU) after sudden cardiac arrest due to ventricular fibrillation (VF) and suspected acute coronary syndrome (ACS). After being treated with shock by Automated External Defibrillator (AED), an electrocardiogram (ECG) demonstrated sinus tachycardia with antero-lateral ST-segment Elevation. Initial Transthoracic echocardiography (TTE) showed severe and diffuse left ventricular (LV) dysfunction and dilatation. Coronary angiography revealed anomalous origin of the LCA from the PA and extensive collateral circulation from a giant RCA. An ECG gated cardiac computed tomography (CT) confirmed the diagnosis of anomalous LM originating from the left pulmonary artery. Cardiac magnetic resonance (CMR) demonstrated an enlarged left ventricle with globally reduced function, and extensive sub-endocardial scarring of the anterior, anterolateral and lateral walls. Following a multidisciplinary heart team discussion, the patient successfully underwent repair of aberrant LCA with direct LCA re-implantation to the aorta and subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation. Optimal medical therapy (OMT) for heart failure with reduced ejection fraction (HFrEF) was initiated and the patient was discharged home for a close clinical and echocardiographic follow up. In conclusion ALCAPA in the adulthood is a very rare congenital anomaly that clinicians should be aware of. The preferred treatment, when diagnosed in time, is direct re-implantation of the LCA to the aorta.

Integrating Out-of-Pocket Costs Into Shared Decision-Making for Heart Failure With Reduced Ejection Fraction: A Stepped-Wedge Trial (POCKET-COST-HF).

Guideline-directed medical therapy for heart failure (HF) with reduced ejection fraction can entail high out-of-pocket (OOP) costs, prompting concerns about financial toxicity and access. OOP costs are generally unavailable during encounters. This trial assessed the impact of providing patient-specific OOP costs to patients and clinicians. This trial was conducted between June 2021 and August 2023 at 6 clinics in 2 health systems using a stepped-wedge, clinic-level cluster-randomized design. Adult patients with HF with reduced ejection fraction (left ventricular ejection fraction ≤40%) were enrolled. The intervention was built upon the EPIC-HF (Electronically Delivered, Patient-Activation Tool for Intensification of Medications for Chronic Heart Failure with Reduced Ejection Fraction) checklist of approved HF with reduced ejection fraction medications. Patients and clinicians received this checklist with (intervention) or without (control) patient-specific OOP cost estimates for higher-cost medications at the time of encounter. Estimates were obtained by providing pharmacy benefit information to a financial navigation firm. Encounters were audio-recorded, and patients were surveyed 2 weeks later. The primary outcome was cost-informed decision-making, defined by mentioning HF medication cost during the encounter. The primary analysis used a generalized linear mixed model. Secondary outcomes were assessed via transcript subcoding and analysis of survey responses. Demographic characteristics of 247 patients (mean age, 62.9 years; 29.5% female; 26.3% Black; and 3.2% Hispanic/LatinX) treated by 39 clinicians in intervention and control periods were similar. In the primary model, the rate of cost-informed decision-making was higher in the intervention group than the control group (68% versus 49%; P=0.021). Baseline rates of cost discussions and the impact of the intervention varied across sites. When cost discussions were present, fewer discussions in the intervention group involved contingency plans to address potential costs (16.5% versus 31.9%; P=0.028). Most other secondary outcomes were not significantly different. Disclosing comprehensive OOP medication costs to patients with HF with reduced ejection fraction increased cost-informed decision-making. Further work is needed to optimize implementation and assess the impact on medication choices and adherence. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04793880.

Health insurance and clinical outcomes in patients with chronic heart failure in Latin America: an observational study of the Colombian Heart Failure Registry (RECOLFACA).

The effect of the health insurance type on the prognosis of heart failure (HF) patients in Colombia and Latin America is poorly known. We aimed to analyze the characteristics of HF patients that participated in the Colombian Heart Failure Registry (RECOLFACA) as stated by their health insurance type and their relationship with the immediate prognosis of these patients. Patients with HF diagnosis were included in the RECOLFACA registry between 2017-2019. The registry was conducted in 60 centers in Colombia. All-cause mortality was the principal outcome. To evaluate the impact of health insurance on mortality, a Cox proportional hazards regression model was used. The Kaplan-Meier analysis was performed to compare survival probabilities according to insurance type. All statistical analyses were two-tailed and were considered significant with a p value < 0.05. Of the 2,528 participants enrolled in the registry, 99% held details about their health insurance. Of those, 897 patients (35.6%) were covered by public insurance. These patients were significantly younger, with a lower proportion of men, more frequently from rural origin, and lower prevalence of most comorbidities (omitting hypertension, chronic obstructive pulmonary disease (COPD), and Chagas disease) than those with private insurance. Furthermore, patients with public insurance had a worse functional class, as well as a poorer quality of life, and lower frequency of use of implantable devices, while exhibiting similar prescription rates of triple medical therapy for HF. Finally, no differences in short-term mortality were observed between the two groups (HR 1.09; 95% CI 0.79, 1.51). The type of health insurance represents a condition related with relevant differences in the profile of patients with HF in Colombia. Despite this, no significant differences were detected in the short-term prognosis of these patients based on the type of health insurance.

Cardiac remodelling in the era of the recommended four pillars heart failure medical therapy.

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.

Growth Hormone Therapy in Chronic Heart Failure: a Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Guideline-directed medical therapy of heart failure (HF) primarily targets neurohormonal activation. However, growth hormone (GH) has emerged as a potential treatment for the multiple hormonal deficiency syndrome, which is associated with worse outcomes in HF. This study evaluates the efficacy and safety of GH therapy in HF. A systematic search was conducted in PubMed, Cochrane Library, and ClinicalTrials.gov, according to PRISMA guidelines. Randomized, placebo-controlled trials studying GH therapy in adult HF patients were included. Of the 1,184 initially identified records, 17 studies (1.4%) met the inclusion criteria. Two independent authors conducted the search, with any disagreements resolved by a third author. Study quality was assessed using predefined criteria, including randomization, blinding, and the presence of a placebo group. A random-effects model was applied due to heterogeneity across studies. GH therapy significantly improved left ventricular ejection fraction (3.34%, 95% CI: 1.09% to 5.59%, p=0.0037), peak oxygen consumption (2.84 mL/kg/min, 95% CI: 1.32 mL/kg/min to 4.36 mL/kg/min, p=0.0002), and New York Heart Association class (-0.44, 95% CI: -0.08 to -0.81, p=0.023). GH therapy also reduced the composite of death, worsening HF or ventricular tachycardia by 41% (95% CI: 0.39-0.90, p=0.013). Subgroup analyses indicated that patients with ischemic cardiomyopathy, baseline ejection fraction ≥30% and longer treatment duration experienced greater benefits. GH therapy may improve cardiac function, exercise capacity, and HF symptoms, with a trend towards improvement in hard endpoints, such as worsening HF. Event-driven trials are necessary to validate these findings.

Abstract 4113961: Contemporary Guideline Directed Medical Therapy in Heart Failure in Clinical Practice - Results from the EMPACE Study

Background: Guideline directed medical therapy (GDMT) for heart failure (HF) evolves, incorporating newer therapies such as SGLT2i within recommendations for HFmrEF and HFpEF. Understanding the contemporary profile of real-world HF patients, in combination with real-world utilization of GDMT, is important for informing GDMT implementation and quality improvement strategies. The EMPACE study aims to improve our comprehension of HF GDMT utilization in real-world settings during post-2020 . Objectives: To describe baseline demographic and clinical characteristics, including baseline treatments, of patients with HF hospitalization (HHF). Methods: This non-interventional, retrospective cohort study used patient data standardized to the OMOP Common Data Model from the Optum Market Clarity, an integrated EHR and Claims database in the U.S. The study period spanned from Jun-2020 to Oct-2023. Adult patients with a primary diagnosis of HF during hospitalization were stratified by HF phenotypes (HFrEF, HFmrEF, HFpEF) based on left ventricular ejection fraction (EF). Results: A total of 30,762 patients with HHF were included (74% HFrEF, 4% HFmrEF, and 22% HFpEF). The mean age was 70.1 years, 60% were male, mean BMI was 30.6 kg/m 2 , and mean eGFR was 58.7 mL/min/1.73m 2 . Of them, 72% had a history of HF and 43% has been previously hospitalized for HF in the past 1 year. The prevalence of baseline comorbidities was as follows: hypertension (90%), coronary artery disease (54%), chronic kidney disease (38%), atrial fibrillation (40%), peripheral artery disease (9%), stroke history (9%), and end-stage renal disease (1%). Medication prior to HF hospitalization are described in the figure 1. Overall, prior comorbidities and HF medication use in the last 365 days prior to HHF were similar between all HHF patients and the HFrEF, HFmrEF, and HFpEF phenotypes, except for the lower use of MRA and ARNI in HFmrEF, and HFpEF patients. Conclusion: This study showed a high comorbidity burden and a low utilization of many GDMT prior to hospitalization, especially for novel GDMT (ARNI and SGLT2i) and in HFmrEF and HFpEF. Despite many medications having a varying strength of guideline recommendation depending on EF, absolute differences in rates of GDMT utilization were relatively small across the EF phenotypes. Across the spectrum of EF, further efforts are needed to improve use of GDMT and reduce the missed opportunities for GDMT implementation that are occurring prior to HHF.

Abstract 4124531: Digital Health Intervention to Enhance Optimization of Heart Failure Care: From Reciprocal Innovation using Human-Centered Design to Pilot Study

Introduction: Guideline-directed medical therapy (GDMT) for Heart Failure with reduced ejection fraction (HFrEF) reduces adverse events by 70%, but is underutilized. The Human Centered Design (HCD) methodology can be useful to build a strategy to optimize GDMT centered on patients’ demands and perspectives. We aimed to reciprocally innovate a telephone-based digital health intervention (DHI) from a Brazilian trial to an app co-developed for a US trial and iterate it again to the Brazilian context using HCD. We will evaluate the app’s usability and utility to facilitate HF GDMT optimization, considering barriers of the Brazilian public health system users, such as low literacy and socioeconomic status. Methods: Mixed methods study. Steps were carried out according to HCD method: (1) empathizing and identifying challenges, (2) suggesting solutions, (3) prototype development, (4) ranking features for feasibility and utility (5) engineering work and (6) prototype testing. In stages 1-3, semi-structured interviews were held with 10 HF patients and 2 health professionals. Steps 4 and 5 were done by the research team. In stage 6, we conducted a pilot study with 10 HFrEF patients, with at least one GDMT drug with an optimization gap. The primary outcome was the app’s usability assessed by an engagement score, and the app’s utility at 4 weeks. Secondary outcomes included change in self-care score using the European Self-Care Behavior Scale. After step 6, new interviews were carried out to capture the user experience and identify new iterations. Interviews were recorded and transcribed for content analysis. Results: The average engagement score was 80% (SD 16) and the app’s utility score was 82% (SD 8). The average self-care score increased by 32% (SD 25) at the end of the pilot. The main challenges were lack of knowledge about HF and self-care. Technical difficulties and lack of trust in the app to handle health data were mentioned. In the pilot, patients reported the app was easy to use and contributed to self-care and understanding of HF. Among the DHI components, teleconsultation was best evaluated, followed by the educational videos. The greatest challenge was connecting the blood pressure cuff and scale via Bluetooth. Conclusion: The app was well accepted and considered useful by patients. User contributions were fundamental to create tools that facilitate engagement and utility. The final product will be evaluated in a randomized, multicenter, clinical trial.

Abstract 4124293: Exercise Capacity in Patients with Fontan Physiology

Introduction/Background: In the absence of a sub-pulmonary ventricle in the Fontan circulation, augmentation of pulmonary blood flow and filling of the systemic ventricle during exercise are limited. Cardiopulmonary exercise testing (CPET) is a reliable method for evaluation of aerobic capacity, gas exchange, and other physiologic parameters used for risk stratification in this population. Despite the ubiquitous use of CPET, reference ranges for patients with Fontan physiology are limited. The purpose of this study is to describe exercise characteristics and their relationship with different characteristics of Fontan physiology, imaging, and hemodynamics. Methods/Approach: In this retrospective cohort study, CPET results were reviewed for adult Fontan patients at the University of Washington between May 2021 and February 2024. Demographics, comorbidities, medications, type of Fontan conduit, imaging characteristics, hemodynamics, and exercise characteristics were included. Results were compared to a large previously published cohort of Fontan patients. Univariate linear regression was used to identify associations between demographics, cardiac anatomy, and exercise parameters. A p-value of less than 0.05 was considered statistically significant. Results/Data: Baseline demographics were notable for an older patient population (31±7 years) with lower indexed peak VO 2 (20.5±5.6 mL/kg/min) and greater V E /VCO 2 slope (37±7) compared to the historic cohort. Indexed peak VO2 was associated with age, BMI, type of Fontan conduit, FEV1, FVC, resting oxygen saturation, peak systolic blood pressure, and peak heart rate. Indexed peak VO 2 was notably not significantly associated with sex, systemic ventricular morphology, ventricular systolic function, Fontan pressure, or the presence of conventional heart failure medical therapy. Conclusions: In the growing population of older patients with Fontan physiology, development of age-specific population normative data may increase the clinical utility of CPET. Further investigation of the relationship between imaging characteristics, hemodynamics, and exercise parameters is needed in the Fontan population.

Aggressive Intravenous Hydration and a Defined Plant-Based Diet Safely and Effectively Treated Type 5 Cardiorenal Syndrome with Stage E Heart Failure-Related Cardiogenic Shock: A Case Report

Background and Clinical Significance: Heart failure and kidney diseases often coexist and are difficult to clinically manage. Dysfunction in either organ exacerbates dysfunction in the other, potentially leading to cardiorenal syndrome (CRS). CRS has five different subtypes, with CRS type 5 being the most problematic given that it consists of an acute insult superimposed upon chronic CRS. Additionally, type 5 CRS can be complicated by heart failure-related cardiogenic shock (HF-CS), which is associated with increased hospitalizations and has a high 1-year mortality rate. The standard treatment for patients with HF-CS consists of guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF) as tolerated, along with inotropic therapies and surgical mechanical left ventricular (LV) support, guided by invasive hemodynamic monitoring. Case Presentation: This case study reports the presentation of a 57-year-old man who presented with type 5 CRS who rapidly decompensated to stage E HF-CS and was effectively and safely treated with aggressive intravenous hydration, a defined plant-based diet (DPBD), and reduction of guideline-directed prescription medications without invasive hemodynamic monitoring. Conclusions: Hydration, a DPBD, and a reduction in medication burden may be effective in CRS. Pilot studies are warranted to evaluate the efficacy of this intervention in CRS in a larger cohort.

Stakeholder Perspectives on a Heart Failure With Reduced Ejection Fraction Polypill: A Multi-Center Mixed Methods Study.

A polypill containing all 4 classes of guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF) has been proposed to change the heart failure treatment paradigm. The acceptability, appropriateness, and feasibility of a HFrEF polypill-based strategy are unknown. The purpose of this study was to elicit patients' and providers' priorities in the design of HFrEF polypills. From April 2023 to December 2023, we conducted a convergent parallel mixed-methods study at Washington University in St. Louis, the University of California, San Francisco, and the American College of Cardiology. We administered physician surveys containing adapted implementation outcome measures to elicit physicians' perspectives on the acceptability, feasibility, and appropriateness of a HFrEF polypill (Likert scale ranging from 1 [low] to 5 [high]). We used a purposive sampling frame to select patients and physicians for in-depth interviews. Using semi-structured interview guides, we elicited participants' perspectives on current HFrEF care, HFrEF polypill design, and supportive strategies. The Consolidated Framework for Implementation Research v2.0 guided thematic analysis. Of the 214 survey respondents across the United States, physicians agreed that HFrEF polypills are highly acceptable (mean [SD], 4.2 [0.7]), highly appropriate (4.1 [0.8]), and highly feasible (4.1 [0.7]). Key themes from 9 patient and 22 provider interviews included the following: (1) current determinants of HFrEF care, including medication adherence, variations in clinical practice, and health care access, (2) provider-level differences in preferred HFrEF polypill design, (3) cost and equity considerations in the implementation of HFrEF polypills, and (4) research priorities for evaluating polypill effectiveness and implementation. A HFrEF polypill-based strategy was viewed as highly acceptable, appropriate, and feasible by patients and physicians. Participants described key priorities in HFrEF polypill design, titratability, and potential impacts on health equity that will directly inform future randomized controlled trials.

Impact of discharge checklist on guideline-directed medical therapy and mid-term prognosis in heart failure.

Despite the proven benefit of the guideline-directed medical therapy (GDMT), it remains underutilized in patients hospitalized with acute heart failure (HF). We aimed to evaluate the impact of the discharge checklist on GDMT installation and the prognosis of HF patients. This study was a single-center, observational study that included all patients admitted for HF from March 2021 to February 2023. The data were retrieved from electronic medical records and discharge checklists. A comparison was conducted between the checklist group and the non-checklist group. The primary endpoint was a composite of all-cause mortality or readmission for HF within 6 months. The checklist was completed for 537 patients (checklist group) and not for 187 patients (non-checklist group). The proportion of patients to whom two or more components of GDMT were prescribed was significantly higher in the checklist group than in the non-checklist group (59.6% vs 42.2%, p < 0.001). The checklist group exhibited a significantly lower primary outcome compared to the non-checklist group (27.4% vs. 36.4%, HR 0.73, 95% CI 0.55-0.98, p = 0.036). The effect of the checklist was more prominent in HF with reduced ejection fraction (HR 0.51, 95% CI 0.34-0.77, p = 0.001) than in HF with mildly-reduced and preserved ejection fraction (HR 0.91, 95% CI 0.58-1.42, p = 0.676) (p for interaction = 0.06). The implementation of the discharge checklist was associated with an improvement in GDMT prescription and an improved prognosis in patients with HF with reduced ejection fraction.

Early Heart Failure Outcomes and Medical Therapy Use in a Virtually Managed Hospital-at-Home Setting

Early Heart Failure Outcomes and Medical Therapy Use in a Virtually Managed Hospital-at-Home Setting

Evaluating the budget impact of Empagliflozin in managing heart failure with reduced ejection fraction: Proposing strategic policies for Malaysian public healthcare.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors such as Empagliflozin, are increasingly recommended as part of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) in many developed nations. This recommendation is based on robust clinical evidence showing that adding Empagliflozin to GDMT improves heart failure symptoms, clinical outcomes, functional status, and overall quality of life. In Malaysia, where healthcare is predominantly public and heavily subsidized, the introduction of new treatments can significantly impact costs, requiring detailed economic assessments. This study evaluates the budget impact of incorporating Empagliflozin into GDMT for HFrEF from the perspective of the public healthcare system. A five-year budget impact model was developed, integrating local data such as population, drug use, costs, clinical outcomes, and healthcare expenses. In the current scenario (GDMT alone), the projected five-year expenditure is MYR 6.12 billion (USD 3.92 billion). With Empagliflozin, the total cost rises by 0.71% to MYR 6.16 billion (USD 3.95 billion), driven by drug acquisition costs of MYR 160.12 million (USD 102.64 million) and adverse event costs of MYR 211,543 (USD 135,604). However, these costs are offset by savings from reduced HF hospitalizations, fewer cardiovascular deaths, and improved renal outcomes. Sensitivity analysis identified hospitalization costs, the price of Empagliflozin, and cardiovascular deaths in diabetic patients as key factors influencing the budget impact. Policymakers can improve the affordability of Empagliflozin through strategies like price negotiations, cost-sharing, and focusing on high-risk groups to optimize healthcare expenditure while ensuring effective treatment access.

Mechanisms affecting the neutrophil to lymphocyte ratio in heart failure: a prospective CMR study

Abstract Background The neutrophil-to-lymphocyte ratio (NLR) is a simple measure of inflammation defined as the ratio of the neutrophils to lymphocytes as measured in the full blood count. It is well known that patients with heart failure (HF) have elevated levels of pro-inflammatory cytokines. It has been demonstrated in a recent meta-analysis that elevated NLR in heart failure is significantly associated with worse outcomes including all-cause mortality, heart failure readmissions and cardiovascular death. Purpose Given this association between NLR and adverse prognosis in HF, we aim to identify which factors are associated with an elevated NLR. This may help to recognise patients at higher risk and guide management. Methods Patients with newly diagnosed HF and left ventricular ejection fraction &amp;lt;50% on referral echocardiogram were prospectively recruited at the time of referral for cardiovascular magnetic resonance (CMR). Exclusion criteria included prior revascularisation, myocardial infarction, anginal chest pain, congenital heart disease and suspected myocarditis. In one appointment patients (N=599) underwent clinical assessment, medication review, full blood count and CMR. The CMR protocol included quantitative assessment myocardial blood flow at stress and rest, assessment of ischaemic and non-ischaemic fibrosis by late gadolinium enhancement imaging and T1 and T2 mapping. Guideline directed medical therapy was determined by the referring physician. Baseline demographic data, medication and MRI results were recorded for all patients. NLR was calculated from full blood count and split into tertiles. Clinical and CMR parameters were compared between tertiles by analysis of variance and chi squared test. Results See Table 1 The factors which were found to be significantly associated with an elevated NLR were age, atrial fibrillation, NTproBNP, diuretic dose, inducible ischaemia and ischaemic fibrosis. Of note there was no significant difference between groups in terms of guideline directed medical therapy use or other CMR parameters. Conclusion NLR is increasingly recognised as a marker of adverse risk in patients with heart failure. This prospective study of 599 heart failure patients with reduced ejection fraction has identified that an elevated NLR is associated with: 1. Evidence of congestion as evidenced by NTproBNP results and increased diuretic doses. 2. Occult coronary artery disease as shown by greater levels of inducible ischaemia and ischaemic fibrosis. These findings suggest that the adverse prognosis associated with elevated NLR in heart failure may be mediated by worsening congestion and occult coronary artery disease. Importantly there was no association between myocardial inflammation or oedema (measured as native T1 and T2) and NLR. Whether NLR improves with medical therapy of heart failure remains to be established and our findings need to be validated in more varied cohorts of patients with heart failure.

Secondary erythrocytosis / polycythemia due to sodium glucose co-transporter 2 inhibitors: a real world heart failure cohort

Abstract Background Sodium glucose co-transporter 2 inhibitors (SGLT2-i) are one of the four pillars of guideline-directed medical therapy in heart failure with reduced ejection fraction and preserved ejection fraction according to the current ESC and AHA/ACC heart failure guidelines 1,2. As a result, there has been a significant increase in their use worldwide. Although SGLT2 inhibitors are known to increase hemoglobin and hematocrit levels, there is a lack of data on the burden of erythrocytosis or polycythemia in pivotal trials 3,4. Purpose In this retrospective cohort study, we investigated the prevalence and clinical outcomes of SGLT2-i related erythrocytosis in a tertiary heart failure outpatient clinic. Methods We reviewed clinical data from heart failure patients treated with an SGLT2 inhibitor at our tertiary centre between September 2019 and October 2023. Patients were included if they were taking SGLT2-i continuously for more than one month. Data were collected on Hb/Hct levels at baseline before initiation of SGLT2-i, at peak levels during therapy and at the last follow-up. Erythrocytosis was defined according to the 2017 WHO classification as Hb&amp;gt; 10.3 mmol/L and/or Hct&amp;gt; 49% in men and Hb&amp;gt; 10.0 mmol/L and/or Hct&amp;gt; 48% in females. Results A total of 173 patients with heart failure were included (median age 58 [49-66] years, 65% male). One hundred and fifty-six patients (90%) were using dapagliflozin, while 16 patients (9%) were using empagliflozin. The overall prevalence of SGLT2i related erythrocytosis was 39/173 (22.5%; median age 60 and 82% males). Eleven (6.3%) patients had pre-existing erythrocytosis at baseline. During a mean follow-up of 14±10 months, 28/173 (16.2%) patients developed new onset erythrocytosis. The median time to the peak of the Hb/Hct level was 6.5 months. Although the group with erythrocytosis had significantly higher Hb and Hct at baseline compared to the group without erythrocytosis (Hb 9.7 mmol/L ± 1.0 vs. 8.5 mmol/L ± 1.0; p&amp;lt;0.001 in men and 9.1 mmol/L ± 0.8 mmol/L vs. 8.1 ± 0.8; p=0.006 in females), they also experienced a significantly greater median increase in Hb from baseline to peak (1.05 mmol/L vs. 0.60mmol/L; p=0.01) (see Figure 1) There were significantly more males (82% vs 60%; p=0.01) in the erythrocytosis group compared to the non-erythrocytosis group. In addition, the prevalence of OSAS was significantly higher in the group with erythrocytosis compared to the group without erythrocytosis (31% vs. 8%; p&amp;lt;0.001). Conclusion Secondary erythrocytosis or polycythemia is common in patients with chronic heart failure. It is particularly common in men and in patients with obstructive sleep apnoea syndrome (OSAS). There were no excess thrombotic or thromboembolic events, probably because of the routine use of anticoagulants/antiplatelets and limited follow-up. To avoid unnecessary haematological referrals and potential clinical adverse events, increased awareness among clinicians is needed.Table 1.Baseline and clinical outcomesFig1.Hemoglobin levels over time

Utilization and safety of digoxin in patients with chronic heart failure and atrial fibrillation with rapid ventricular rate

Abstract Background Digoxin can reduce symptoms and the risk of tachycardia-induced cardiomyopathy in patients with heart failure (HF) and concomitant atrial fibrillation (AF) with rapid ventricular rate. The effect of digoxin in HF and AF has not been tested in randomized controlled trials, and observational data have shown conflicting results linking digoxin to increased mortality in AF, though the nature of observational data makes it prone to bias and results difficult to interpret. Purpose To assess the utilization of digoxin in patients with HF and AF, and its association with New York Heart Association (NYHA) functional class and survival. Methods We used data from the Norwegian HF registry that collected data from all Norwegian HF clinics between 2013-2022. Data was collected from the first and last visit during optimizization of HF medical therapy. Associations with mortality status from Statistics Norway were assessed in unadjusted time-to-event analysis, and after adjustment for age, sex, body mass index, estimated glomerular filtration rate, aldosterone antagonists, renin-angiotensin-aldosterone system inhibitors, and beta blockers. Results The study included 4,877 HF patients, consisting of 4,067 (83.4%) with ejection fraction (EF) ≤40% and 810 (16.6%) with EF &amp;gt;40%.. The mean age was 67.7±12.0 years; 25.1% were women, and 27.3% had NYHA functional class III/IV. At the first visit, 1,339 (27.5%) patients had AF and 829 (61.9%) of these were treated with ≥50% of the beta-blocker target dose. AF with a ventricular rate ≥100 bpm was present in 277 (20.1%) patients, and 188 (67.9%) of these were on ≥50% beta-blocker target dose. Similarly, 262 (19.6%) of all AF patients and 44 (15.9%) of those with a ventricular rate ≥100 bpm were treated with digoxin. After optimization of HF medical therapy (median duration 140 [Q1–Q3 82–237] days), 1,039 (21.3%) patients had AF. Among these, 227 (21.9%) were treated with digoxin, including 9 (18.0%) patients with ventricular rate ≥100 bpm. Patients with AF who were started on digoxin experienced during the optimization period a larger decline in heart rate compared to those who were not (mean change -23.7±17.2 vs. -5.7±16.7 bpm, p=0.001), and more often an improvement in NYHA functional class (45% vs 30%, p=0.018). During median 779 [Q1–Q3 386–1,334)] days of follow-up after the last optimization visit, digoxin use was associated with lower mortality in HF patients with AF in unadjusted analysis (HR 0.67 [0.46–0.97]). After adjustment for baseline characteristics and other HF medical therapies, the association with mortality was attenuated and no longer significant (HR 0.96 [0.65–1.42]). Conclusion Digoxin was infrequently used in patients with HF and AF with rapid ventricular rate but was associated with a greater decrease in heart rate and improvement in NYHA functional class. The use of digoxin appears safe and was not associated with increased mortality.

ICARUS registry: findings from the first 1595 cases of acute decompensated heart failure in a single center in a latin american country

Abstract Introduction Institutional aCute decompensAted HeaRt FailUre RegiStry (ICARUS) will provide information on clinical characteristics, medical practice, patterns of treatment, and outcomes of patients hospitalized with Acute Decompensated Heart Failure (ADHF) in a hospital in a middle-income country. Objective Describe the methodological aspects, sociodemographic, and clinical characteristics of patients hospitalized with ADHF and their short-term outcomes. Method Prospective cohort of patients with ADHF from the emergency service of a cardiovascular center. Descriptive statistics were used to synthesize sociodemographic characteristics, clinical characteristics during hospitalization, and outcomes. Results 1595 patients with ADHF. The median age was 68 years (Q1=58; Q3=76), and 69.28% were men. The median hospital stay was six days (Q1=4; Q3=11), with an accumulative incidence (AI) for rehospitalization at 30 days of 8.70 % (95% CI 7.18 to 10.40%), in-hospital mortality AI of 4.33% (95% CI 3.38 to 5.44%), and a median change in the quality-of-life score like Minnesota Living with Heart Failure Questionnaire (MLHFQ) at 30 days of -20 points (Q1=-37; Q3=-5). At discharge, all patients had a percentage greater than 70% of the use of quadruple neurohormonal blockade therapy. Conclusions ICARUS is one of the first registries in Latin America since the indication of the use of SGLT2 inhibitors, evaluating the clinical and sociodemographic characteristics, treatment patterns, and outcomes of a preliminary cohort of 1595 patients hospitalized for ADHF. The results indicate that, at discharge, up to 82.79% of patients were receiving quadruple neurohormonal blockade therapy, which is considerably challenging to achieve in Latin America. Considering the results of the Safety, tolerability and efficacy of up-titration of Guideline-Directed Medical therapies for acute heart failure (STRONG-HF study), our study reinforces the benefit of discharge with Guideline-Directed Medical Therapy (GDMT) for heart failure from hospitalization. The use of GDMT for heart failure may have influenced our positive outcomes in terms of in-hospital mortality, improvement in quality of life, and the percentage of short-term rehospitalizations compared to similar cohorts.Proportion of HF drug group

The impact of comorbidities on therapy-optimization and their prognostics role among hospitalized patients with heart failure with reduced ejection fraction

Abstract Background The early, accurate diagnosis and proper treatment of comorbidities (CMs) are of strategic importance in heart failure (HF), as stated in the current ESC HF Guidelines. Unquestionably, the presence of CMs is associated with worse prognosis. Moreover, CMs can unfavourably affect the implementation of the guideline-directed medical therapy (GDMT) in heart failure with reduced ejection fraction (HFrEF). Aim To assess the prevalence of the relevant prognosis-modifying CMs among patients requiring hospitalization due to HFrEF, investigate their effect on the implementation and optimization of GDMT, and examine the impact of the presence of CMs on the prognosis in HFrEF. Patients and methods The data of 313 patients requiring hospitalization at our Institution due to HFrEF between 2021-2023 (male: 77%, age: 60[50-70]years, coronary artery disease: 46%, diabetes: 36%, hypertension: 65%, atrial fibrillation: 42%, LVEF: 24[20-30]%, eGFR at admission: 57[46-74]mL/min/1.73m², NT-proBNP at admission: 5035[2376-9369]pg/mL, SBP: 121[110-140]mmHg; GDMT at admission - RASi[ACEi/ARB/ARNI]: 60%, βB: 59%, MRA: 44%, SGLT2i: 14%) were analyzed retrospectively. Based on the number of diagnosed CMs, patients were divided into 3 categories: 0-1 vs. 2-3 vs. ≥4 CMs. The implemented GDMT at discharge was compared among CM categories with Chi-square test, while all-cause mortality (ACM) rates were investigated with Kaplan-Meier method and multivariate Cox-regression analysis. Results During the hospitalization in the total cohort the proportion of patients on GDMT increased significantly (RASi: 91%, βB: 85%, MRA: 96%, SGLT2i: 57%; patients on triple [TT] therapy [RASi+βB+MRA]: 83%, patients on quadruple therapy [TT+SGLT2i]: 52%; p＜0.05). However, among patients with higher rates of CMs, the application of GDMT was less favourable (RASi: 97% vs. 94% vs. 82%; βB: 93% vs. 89% vs. 75%; p＜0.05; 0-1 vs. 2-3 vs. ≥4 CMs), the proportion of patients on TT and QT remained remarkably high even among those with ≥4 CMs (TT: 93% vs. 87% vs. 71%; QT: 65% vs. 52% vs. 45%; p＜0.05). During the median follow-up period of 1.3 year, the ACM of patients with increased burden of CMs was higher (12% vs. 18% vs. 37%, p＜0.001). According to the results of the multivariate Cox-regression analysis, more advanced left ventricular systolic dysfunction (/1%), previously confirmed diagnosis of HFrEF, the growing number of CMs proved to be negative independent predictors of ACM, while the application of TT or QT reduced the risk of ACM significantly (HR: 0.471, 95% CI: 0.271-0.819, p=0.008). Conclusions According to our real-world analysis, although among HFrEF patients with an increased burden of CMs, less favourable prognosis can be expected, the application of modern GDMT is even possible among them, resulting in a significantly improved prognosis. Thus, clinicians should insist on the early, conscious implementation of GDMT among these patients as well.

Temporal trends in sudden cardiac death after acute decompensation in HFrEF patients: a 13-year Japanese multicentre registry study

Abstract Background The implementation of guideline-based medical therapy (GBMT) for heart failure with reduced ejection fraction (HFrEF) has significantly contributed to reducing mortality risks. Yet, detailed analyses on temporal trends of sudden cardiac death (SCD) among these patients, especially post-discharge following acute decompensation, remain scarce. Purpose This study aimed to explore changes in the incidence of SCD over the last 13 years in patients with HFrEF discharged after acute decompensation treatment, and to identify clinical factors associated with SCD risk. Methods We analyzed 2,604 consecutive HFrEF (left ventricular ejection fraction [LVEF] ≤40%) patients enrolled in a Japanese multicentre acute heart failure (HF) registry from 2009 to 2021. SCD was defined as an unexpected and otherwise unexplained death in a previously stable patient or death due to documented or presumed cardiac arrhythmia without a clear non-cardiovascular cause. The determination of death cause (SCD, pump failure death, or other) was made by a central adjudicating committee. The Fine and Gray method was employed to analyze factors associated with SCD. The variables submitted to the model included age (≥70 years), gender, LVEF (&amp;lt;30%), ischaemic aetiology and prescription of GBMT (use of renin-angiotensin system inhibitors, β-blockers and mineralocorticoid receptor antagonist) at discharge. Results The mean age of studied patients was 70.9±14.2 years, and 70.0% were male. During the 1-year follow-up period, 262 deaths (10.1%) occurred, including 51 SCDs (2.0%). Older age was associated with an increased risk of SCD (adjusted hazard ratio [HR] 2.81, 95% confidence interval [CI] 1.40-5.64, P=0.004). Further, patients with an ischaemic aetiology had a higher risk of SCD (HR 1.84, 95% CI 1.06-3.22, P=0.032). During the study period, mean age remained constant (71.0 years to 70.7 years, P for trend =0.884). The proportion of ischaemic aetiology also remained constant (from 37.2% to 38.2%, P for trend =0.972). Overall, there were significant decreases in the incidence of all cause death and SCD (from 13.7% to 8.4%, P for trend =0.002; and from 3.5% to 1.0%, P for trend &amp;lt;0.001; Figure A). Notably, there was an increase in the prescription rate of three classes of GBMT at discharge (from 30.9% to 45.6%, P for trend &amp;lt;0.001; Figure B), and the rate of implantable cardioverter-defibrillator (ICD) use in eligible patients (New York Heart Association functional class II-III with LVEF ≤35%) remained constant (from 9.6% to 11.6%, P for trend =0.157; Figure B). Conclusions With the increasing use of GBMT, the incidence of SCD decreased in real-world patients with HFrEF registered in a Japanese acute HF registry over the past decade.