Comorbid Heart Failure Research Articles

P-810. Impact of Comorbid Heart Failure among Hospitalized Patients with Escherichia coli Sepsis: a United States Population-Based Cohort Study

Abstract Background Sepsis-induced cardiomyopathy was deemed an independent predictor of increased risk for morbidity and mortality, especially for those individuals with pre-existing heart failure (HF). Although previous studies suggested that comorbid HF adversely impacted the outcomes of septic patients in general, there is paucity of data looking specifically at its impact among hospital patients with Escherichia coli (E. coli) sepsis. Methods We utilized the National Inpatient Sample (NIS) to identify patients with HF who were hospitalized for E. coli sepsis during the index hospitalization using appropriate ICD-10 codes between 2018-2020. We aim to investigate the impact of HF among E. coli septic patients based on in-hospital mortality, risk for acute respiratory failure and cardiogenic shock, and utilization of mechanical ventilation. A multivariable logistic regression analysis was used to calculate adjusted odds ratios (ORs) for the outcomes of interest. Results A total of 93,896 hospitalized patients with E. coli sepsis were identified, of which 23.51% (22,075/93,896) had concomitant HF during the index hospitalization. The overall in-hospital mortality rate among patients with E. coli sepsis was 8.71% (8,178/93,896). Among those with concomitant HF, the mortality rate was significantly elevated to 13.05% (2,881/22,075, p= < 0.001). After adjusting for possible confounders, concomitant HF in patients with E.coli sepsis was found to be an independent predictor of increased risk for in-hospital mortality (aOR 1.54; 95% CI, 1.34-1.76; p=< 0.001), acute respiratory failure (aOR 2.45; 95% CI, 2.23-2.69; p=< 0.001), cardiogenic shock (aOR 10.11; 95% CI, 7.11-14.39; p=< 0.001), and utilization of mechanical ventilation (aOR 2.00; 95% CI, 1.78-2.24; p=< 0.001) Conclusion Our analysis showed that HF among hospitalized E. coli sepsis patients was associated with an increased risk for adverse outcomes. This is likely due to the hemodynamic alterations in HF that are adversely impacted by sepsis treatment including fluid resuscitation, vasopressor use, and the advanced virulence factors of E. coli in adhesion, toxin production, and iron acquisition. Hence, identification of at-risk patients with HF is needed to mitigate its adverse impact among hospitalized patients with E. coli sepsis. Disclosures All Authors: No reported disclosures

Analysis of clinical features and prognosis in cardiac amyloidosis patients from Spanish hospitals (2016-2021).

Cardiac amyloidosis (CA) is a prevalent yet underdiagnosed heart condition characterized by the abnormal accumulation of amyloid fibres, frequently resulting in heart failure (HF), particularly in older people. Despite advancements in non-invasive diagnostic techniques and treatments, the epidemiology of CA patients remains inadequately understood. This nationwide retrospective observational study sought to comprehensively investigate CA patients' characteristics, mortality, and readmission patterns. A retrospective observational study encompassed all patients hospitalized with CA between 2016 and 2021 across Spanish hospitals. Standardized incidence rates were calculated using age and sex-adjusted methods, utilizing the Spanish population as the reference. The investigation delved into demographic variables, comorbidities, mortality during the index episode, and 30 and 365-day readmissions for circulatory system diseases. Predictors of readmission were also examined. A total of 5,739 index episodes were identified, with CA being the primary cause of admission in 14.1% of cases. The mean age was 81.4 ± 9.9 years, predominantly males (70.3%). The age and sex-standardized hospital attendance rate was 3.90 admissions per 100,000 population (95% CI: 3.82-3.98), higher in males. Common comorbidities included HF (96.4%), atrial fibrillation (46.3%), and renal failure (44.4%). The mortality rate during the index episode was 11.7%, with cardiogenic shock (OR: 9.03; 95% CI: 4.22-19.32) and major psychiatric disorders (OR: 3.36; 95% CI: 1.42-7.94) identified as predictors. Over the follow-up period, 13.1% were readmitted at 30 days and 36.6% at 365. Nephritis (IRR: 2.05; 95% CI: 1.42-2.96) and asthma (IRR: 1.52; 95% CI 1.11-2.07) were associated with increased 30-day readmissions, while renal failure (IRR: 1.43; 95% CI: 1.28-1.59) and chronic pulmonary disease (IRR: 1.40; 95% CI: 1.18-1.67) were linked to higher 365-day readmissions. Predictors of mortality risk in 365-day readmissions included advanced cancer (HR: 1.31; 95% CI: 1.00-1.71), cardiogenic shock in the index episode (HR: 2.72; 95% CI: 1.33-5.57), and a higher number of readmissions during that period (HR: 1.64; 95% CI: 1.56-1.73). This study contributes valuable insights into the significant prevalence of CA, which is often overlooked and underestimated. Afflicting predominantly elderly males with concomitant HF and multiple comorbidities, CA poses a significant clinical challenge. The findings underscore the need for enhanced awareness, early detection, and a multidisciplinary approach to manage this complex cardiac condition.

Features of comorbidity of chronic heart failure and chronic kidney disease in patients infected with the human immunodeficiency virus

THE AIM OF THE STUDY: to identify risk factors associated with the course of chronic kidney disease (CKD), as the main manifestation of damage to the target organ – the kidney, in patients with chronic heart failure (CHF) infected with the human immunodeficiency virus (HIV).PATIENTS AND METHODS. In a multidisciplinary hospital for 28 months in 2019-2022, a one-stage screening clinical study was conducted, which included 240 patients with HIV infection. Of these, 160 people were diagnosed with CHF. Depending on the presence of CKD with a glomerular filtration rate (GFR) <60 mm/min/m2, patients with CHF were divided into 2 groups. The first group consisted of patients with CKD (46 people), and the second group – without signs of CKD (114 people). All patients within the framework of the study underwent the determination of cystatin C in blood serum, the Nterminal fragment of the brain natriuretic peptide (NT-proBNP) in blood plasma, C-reactive protein (CRP) in blood serum, and the quantitative determination of protein in urine.RESULTS. The prevalence of CKD among patients with CHF and HIV infection is 58.82 %, which is 4 times more common than in patients with HIV infection without CHF. Risk factors for the development of CKD in patients with CHF and HIV infection are smoking, alcohol and drug use, a history of chronic and acute forms of coronary artery disease, atrial fibrillation, ventricular arrhythmias, diabetes mellitus, chronic viral hepatitis C, anemia, and thrombocytopenia. Patients with CHF and CKD have a more rigid arterial wall – there is a significant excess of the stiffness indices of the aorta and peripheral arteries. Long-term use of antiplatelet agents and antiretroviral therapy aggravates the course of CHF in HIV-infected people with CKD manifestations. The concentration of NT-proBNP in the blood plasma of patients with CHF equal to or greater than 683.65 pg/ml can be considered as a diagnostic criterion for the development of CKD in HIV-infected people with a sensitivity of the method of 75.0 % and a specificity of 75.4 %, respectively. It has been proven that GFR depends on three main factors that reflect damage to the heart muscle – the concentration of NT-proBNP in blood plasma, the values of LVEF % and LVMI, which together, being included in the regression model, determine 42.2 % of the dispersion of GFR values and are decisive in the development of CKD in patients with CHF on the background of HIV infection.

Inferior vena cava diameter in patients with chronic heart failure and chronic kidney disease: a retrospective study

BackgroundChronic kidney disease (CKD) carries the highest population attributable risk for mortality among all comorbidities in chronic heart failure (CHF). No studies about the association between inferior vena cava (IVC) diameter and all-cause mortality in patients with the comorbidity of CKD and CHF has been published.MethodsIn this retrospective cohort study, a total of 1327 patients with CHF and CKD were included. All patients underwent standardized echocardiography examination and data on demographic characteristics, medical history, and laboratory tests were recorded. Information on all-cause mortality was collected by telephone interview and medical records review. We used Cox regression to evaluate the risk of all-cause mortality among groups, and used mediation analysis to examine the mediation role of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) and serum albumin in the association between IVC and all-cause mortality.ResultsDuring a median follow-up of 3.46 years (IQR: 1.55–5.15 years), 757 (57.05%) cases of all-cause mortality were observed. Compared with patients with IVC diameter < 21 mm, those with IVC diameter > 21 mm were associated with higher risk of all-cause mortality (HR (95%CI):1.31(1.07–1.61), log rank: P = 0.01) and cardiovascular mortality (HR (95%CI): 1.55(1.19–2.04), log rank: P = 0.001). When assessing IVC as a continuous variable, each 1% increase in IVC was associated with 4% increased risk of all-cause mortality (HR: 1.04, 95%CI 1.02–1.06, P < 0.001). This association were mediated by log NT-proBNP (mediated effect: 37.8% (95%CI 22.0–73.0%), P < 0.001) and serum albumin (mediated effect: 14.1% (95%CI 6.2–28.0%), P < 0.001). In subgroup analyses, there was no significant interaction in different subgroups of cardiac and renal function for the association between IVC and all-cause mortality.ConclusionsElevated IVC diameter was associated with worse prognosis in patients with CHF and CKD, and the associations were mediated by log NT-proBNP and serum albumin.

Sex-specific association of comorbid heart failure on mortality after Alzheimer's disease diagnosis in older adults aged 75 years and above: A health insurance claims data analysis in Japan.

Research on the influence of heart failure on mortality after Alzheimer's disease diagnosis is limited. To evaluate the association between comorbid heart failure and mortality following Alzheimer's disease diagnosis, particularly considering sex differences. We analyzed administrative claims data from Japan, involving 32,363 individuals (11,064 men and 21,299 women) aged 75 or older newly diagnosed with Alzheimer's disease, with 7% having comorbid heart failure. Cox proportional hazard models and population attributable fractions (PAFs) were used to evaluate the association between comorbid heart failure and mortality within one year following Alzheimer's disease diagnosis. Individuals with Alzheimer's disease and heart failure had a multivariate-adjusted hazard ratio of 1.51 (95% confidence interval [CI], 1.32-1.73) for mortality during the one-year follow-up period compared to those with Alzheimer's disease and without heart failure. Subgroup analysis by sex revealed a higher mortality hazard ratio in women of 1.63 (95% CI, 1.36-1.95) than that in men of 1.39 (95% CI, 1.13-1.71). Further age and sex subgroup analysis indicated that women across all age brackets-75-79, 80-84, and ≥ 85 years-had higher mortality hazard ratios. The PAF for heart failure increased with age in both sexes, with women having higher PAFs than men, and the sex difference in PAF being most pronounced in the 75-79 age category (men: 1.4%, women: 4.0%). Hazard ratios and PAFs for mortality associated with comorbid heart failure in newly diagnosed Alzheimer's disease are higher in women than in men, which persists across all age subgroups.

Association of Time in Target Range of Resting Heart Rate With Adverse Clinical Outcomes in Patients With Acute Coronary Syndromes After Percutaneous Coronary Intervention.

Heart rate (HR) has been proved to be associated with major adverse cardiovascular events (MACE) in Acute coronary syndrome patients. However, the threshold value and clinical significance of time in target of resting heart rate (TTR-HR) remain insufficiently elucidated. Our study aimed to evaluate the independent association between TTR-HR and cardiovascular outcomes in the follow-up study of ACS. A total of 1455 ACS patients who underwent percutaneous coronary intervention (PCI) and were admitted to 22 hospitals between 2019 and 2022 were enrolled and followed up for 12 months. MACE was defined as a composite of cardiac death, nonfatal recurrent myocardial infarction, ischemic-driven revascularization, and ischemic stroke. The association between TTR-HR and cardiovascular outcomes was assessed using Cox regression model. Compared to patients with TTR-HR 0-50% and >50%-75%, patients with TTR-HR > 75%-100% were older and less alcohol user, less likely to use diuretics and anti-diabetic drugs, these patients had less comorbidities of hyperlipidemia, diabetes, heart failure, and cardiac shock. After 12 months follow up, the incidence of MACE and composite endpoint but not mortality was higher in patients with TTR-HR 0-50% and >50%-75% than those with TTR-HR > 75%-100%. After multivariate adjustment, TTR-HR [hazard ratio = 2.11, 95% CI: 1.19-3.74, p = 0.01] was independently associated with composite endpoint. In summary, our study demonstrates that TTR-HR holds significant prognostic value, with TTR-HR > 75%-100% being independently associated with reduced composite endpoint risk in ACS patients following PCI. These findings emphasize the importance of effective heart rate control in ACS patients following PCI.

Serum creatinine to cystatin C ratio in relation to heart failure with preserved ejection fraction

BackgroundSarcopenia was recognized to be one of the common comorbidities in heart failure (HF). The sarcopenia index (SI), based on serum creatinine to cystatin C ratio, was developed as a simple tool to evaluate skeletal muscle mass but has not been well-studied in the correlation of left ventricular ejection fraction (LVEF). The aim of this study is to analyze the SI in patients with HF, especially patients with HF with preserved ejection fraction (HFpEF), and to develop a prediction model for HFpEF.MethodsThe training cohort included 229 hospitalized patients with HF and 73 healthy controls (HCs) from the Third Affiliated Hospital of Soochow University between December 2019 and February 2022. An additional 78 patients with HF hospitalized at the same hospital between March 2022 to June 2023 were considered as an external validation cohort. Binary logistic regression model was used to analyze the influence factors of HFpEF. A prediction model was constructed and optimized based on the least absolute shrinkage and selection operator (LASSO), displayed by Nomogram and verified internally by Bootstrap with 500 resamples.ResultsSI was significantly different between the HF and HC groups (67.95 ± 13.07 vs. 98.57 ± 31.51) and had a significant negative correlation with LVEF. Multivariate logistic regression demonstrated that SI (OR 0.948, 95% CI 0.914—0.983, P = 0.004) was independently associated with HFpEF. The area under the curve (AUC) for the nomogram constructed based on SI was 0.902. The calibration curve was approximately distributed along the reference line in Bootstrap and the decision curve analysis demonstrated significantly better net benefit in the model. The external validation proved the good predictive performance of the model.ConclusionsLower SI is an independent factor associated with hospitalized patients with HF, especially patients with HFpEF. A prediction nomogram based on SI has good predictive power for HFpEF.Trial registrationThe study was registered with the China Clinical Trials Centre Registry (registration number: ChiCTR2200063401).

Focus on the comorbidities of heart failure: the importance of multidisciplinary management

The diagnosis and treatment of heart failure comorbidities present a significant clinical challenge, as these comorbidities significantly affect patient prognosis. The causes of heart failure comorbidities are complex, and the underlying mechanisms are not fully understood. Moreover, traditional heart failure management methods are inadequate in addressing these issues. Improving the management and treatment of comorbidities can significantly enhance patient quality of life and prognosis. This requires clinicians to have a comprehensive understanding of heart failure and its comorbidities and to be capable of devising effective treatment plans. Multidisciplinary management should be utilized to create individualized treatment plans for heart failure patients to better address the challenges of multiple comorbidities. Clinicians need to have a broad perspective and employ systematic approaches to improve treatment outcomes. This article emphasizes the importance of individualized and multidisciplinary management strategies in the treatment of heart failure comorbidities, aiming to provide a systematic solution to enhance patient quality of life and improve prognosis.

Macrophage NLRP3-dependent IL-1β production contributes to aortic fibrosis in heart failure with preserved ejection fraction.

Fibrosis is the main pathological feature of aortic stiffness, which is a common extracardiac comorbidity of heart failure with preserved ejection fraction (HFpEF) and a contributor to left ventricular (LV) diastolic dysfunction. Systemic low-grade inflammation plays a crucial role in the pathogenesis of HFpEF and the development of vascular fibrosis. In this study, we investigate the inflammatory mechanism of aortic fibrosis in HFpEF using a novel mouse model. LV diastolic dysfunction with preserved ejection fraction and aortic fibrosis induced by a high-fat diet (HFD) combined with subcutaneous aldosterone infusion are utilized. The constructed model exhibits augmented macrophage recruitment and NLR family pyrin domain containing 3 (NLRP3)-dependent interleukin (IL)-1β production in fibrotic aortas. In addition, a bone marrow transplant is employed to induce macrophage-specific NLRP3 deficiency in the HFpEF mouse model. These mice show almost completely suppressed cleaved-caspase-1 and mature IL-1β protein expression in the aortas, indicating that macrophage NLRP3 inflammasome activation enhances the IL-1β overproduction in fibrotic aortas. Furthermore, we show that macrophage NLRP3 inflammasome inhibition improves aortic fibrosis and LV diastolic dysfunction. In conclusion, this study demonstrates the pivotal effect of macrophage NLRP3-dependent IL-1β production on aortic fibrosis and cardiac function in HFpEF, suggesting a potential target for HFpEF therapy.

Exploration of the role of nutritional status scores in heart failure prognosis

Objectives: To explore the prognostic significances of geriatric nutrition risk index (GNRI), controlling nutritional status (CONUT), and prognostic nutritional index (PNI) in patients with heart failure. Methods: This was a retrospective study. Patients with heart failure admitted to the Department of Cardiology, the first affiliated hospital of Sun Yat-sen University from September 16, 2013 to December 28, 2017 were enrolled. Clinical data of patients were collected and patients were followed up. GNRI, CONUT and PNI scores of patients were calculated. Cox proportional risk model was used to evaluate the relationship between the above three nutritional status scores and the risk of all-cause death in patients with heart failure, and restricted cubic spline analysis was used to verify the relationship. Subgroup analysis was performed based on left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, number of heart failure comorbidities, systolic blood pressure, creatinine, body mass index, use of angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists, use of β-blockers, and use of spironolactone. Results: A total of 2 016 patients with heart failure aged (67.7±13.0) years old were enrolled, including 1 230 (61.0%) males. All patients were followed up until September 15, 2021. Multivariate Cox proportional hazard models showed that increased GNRI score was significantly associated with reduced risk of all-cause mortality in patients with heart failure (HR=0.989, 95%CI 0.982-0.996, P=0.001), while CONUT and PNI scores were not associated with all-cause mortality (both P>0.05). Restricted cubic spline analysis showed no U-shaped relationship between the scores and all-cause death. Subgroup analysis suggested that the prognostic value of GNRI score was predominant in patients not using angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (Pinteraction=0.024), while there was no statistically significant difference between groups in other subgroup analyses (Pinteraction>0.05). Conclusions: Increased GNRI score is associated with reduced risk of all-cause mortality in patients with heart failure and may serve as an effective tool to assess nutritional status in patients with heart failure.

A quality improvement model to identify undiagnosed heart failure at chronic obstructive pulmonary disease annual reviews

Abstract Introduction Heart failure (HF) is a common comorbidity in people with chronic obstructive pulmonary disease (COPD). The estimated prevalence of HF comorbidity in patients with COPD is up to 40%1. COPD and HF have overlapping symptoms which could delay the diagnosis of HF. Studies have shown that in UK primary care, HF treatment for COPD patients is delayed by almost twelve months compared to patients without COPD2. Early diagnosis and management of HF for COPD patients in primary care could reduce risk of recurrent exacerbation and subsequent hospitalisation. HF screen is not currently emphasised in the primary care COPD annual reviews. NICE guidance for COPD diagnosis mentions the use of serum natriuretic peptides to aid differential diagnosis of HF3. Pharmacists in general practice are the patients’ first point of contact, they are able to take leading roles in the holistic management of long-term conditions such as HF and COPD. Aim Reduce HF related complication including exacerbations and subsequent hospital admissions for COPD patients through early HF identification programme at COPD annual review. Methods Electronic Emis search was conducted on the practice database to identify patients on the COPD register. Patients with existing diagnosis of HF or NT-ProBNP in the last 12 month were excluded. Patients were invited for COPD annual review and screened for HF symptoms (breathlessness, fluid retention, fatigue, lightheadness) as per NICE guidance for HF identification. NT-ProBNP test was added to routine annual blood test for patients experiencing any of the HF symptoms. Patients with elevated NT-ProBNP &amp;gt;400ng/L were referred for further assessment for suspected HF. The project was a small scale service improvement project, it did not require ethical approval, this was confirmed with the Broad Street Health Centre clinical lead. Results Twenty six patients were screened out of 48 (54 %). Six patients (23%) had NT-pro BNP results over 400ng/L and were referred for further investigation for suspected HF. Diagnosis was confirmed for three patients 11%. Two of the newly diagnosed patients had an MRC score of 3, while one had and MRC score of 2. No patients with MRC score 1, 4 or 5 where among the newly diagnosed group. Discussion Results analysis correlates with published data regarding the prevalence of HF in COPD patients. Screening for HF in primary care might be most beneficial for patients with MRC of 2 or 3. Patients with score of 1 might have milder symptoms however annual screening will allow early detection of future deterioration. There were no newly diagnosed patients from the MRC score of 4 and 5 groups as they might have already been diagnosed if their symptoms were related to underlying HF. The three patients diagnosed with HF were treated for HF as per NICE guidance. Patients’ spontaneous feedback was positive regarding the new management approach. Conclusion Pharmacists in general practice can play a dynamic role in early identification of existing co-morbidities while conducting annual long-term conditions reviews. This in return facilitates vital early interventions to improve prognosis and reduce further complications along the way.

Differences in Pharmacological Treatment of Heart Failure Among Persons with or without Major Cognitive Disorder: A Cross-Sectional Study Based on National Registries in Sweden.

Comorbidities are common among older people, and during the last decade, a strong association between heart failure (HF) and cognitive impairment has been found. As much as 40-50% of individuals with HF will also have some degree of cognitive impairment. Previous studies report an undertreatment for some cardiovascular diseases in patients with major neurocognitive disorder (NCD). The aim of this present study was to explore differences in pharmacological treatment of HF in individuals diagnosed with HF with or without comorbidity of major NCD. This study combined data from three different Swedish national registers: the Swedish National Patient Register, the Swedish registry for cognitive/dementia disorders (SveDem), and the Swedish Prescribed Drug Register. A logistic regression model including variables for age, sex, major NCD, and nursing home residency was used to analyze associations between drug use and major NCD. We found a lower prevalence of filled prescriptions of renin-angiotensin system (RAS) inhibitors, β-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) among patients with major NCD. Living in a nursing home was associated with lower prevalence of RAS inhibitors, BBs, digitalis glycosides, and sodium-glucose cotransporter-2 (SGLT2) inhibitors. Females were found to have higher odds of using BBs, loop diuretics and digitalis glycosides, and lower odds of using RAS inhibitors and SGLT2 inhibitors than males. Our findings indicate that there is possible undertreatment among individuals with HF identified in specialized care with co-occurring major NCD. Major NCD was associated with less filled prescriptions of basal pharmacological treatments such as RAS inhibitors, BBs, and MRAs. Future research needs to not only investigate this relationship further but also focus on reasons for the undertreatment of HF and other comorbidities within this group.

Influence of persistent atrial fibrillation on the prognosis of heart failure with preserved, mildly reduced, and reduced ejection fraction in women and men

Abstract Introduction Heart failure (HF) is one of the leading causes of death from cardiovascular disease. Persistent atrial fibrillation (PAF) is associated with a worse prognosis in HF. However, little is known about the influence of AF on mortality in women and men with heart failure with preserved (HFpEF ≥50%), mildly reduced (HFmrEF 41% to 49%), and reduced ejection fraction (HFrEF ≤40%). Purpose to analyze the characteristics and influence of PAF on the prognosis of different HF phenotypes. Methods From February 2017 to September 2020, we analyzed hospitalizations, emergency admissions, and mortality of different HF phenotypes with and without PAF. Baseline data included clinical features and echocardiographic findings. Statistical analyses were performed using the Kaplan-Meier (K-M) and Cox proportional hazards methods to analyze mortality rates. Results We studied 11,543 patients, with a mean of 64.1±14.0 years: 55.1% male, 42% with HFrEF, 12.8% with HFmrEF, and 45.1% with HFpEF. PAF was associated with higher mean age (67.6±14.3 vs. 62.8±13.4 years, p&amp;lt;0.001) and more prevalent in men (21% vs. 19%; p=0.019) and in patients with valvular and Chagas etiologies, chronic kidney disease (CKD), stroke, and anemia. The prevalence of PAF in women and men was, respectively, 12.4% vs. 18.3% (p&amp;lt;0.001) in HFrEF, 18.1% vs. 22.2% (p=0.029) in HFmrEF, and 23.3% vs. 23.9 (p=NS) in HFpEF. The overall mortality was 21.6%, with mortality being 2.4 times higher in patients with PAF (40.9% vs. 16.7%, p&amp;lt;0.001) compared to sinus rhythm but similar in women and men with PAF (39.5% vs. 41.9%; p=NS), respectively. The hospitalization (30.3% vs 19.4%, p&amp;lt;0.001) and emergency admissions (38.4% vs 25.7%, p&amp;lt;0.001) were higher in patients with AF. Cumulative mortality was higher in patients with PAF in all HF phenotypes: HFrEF (36.6%), HFmrEF (16.8%), HFpEF (46.6%; p&amp;lt;0.001). Men had higher cumulative mortality in HFrEF (18.3% vs. 12.4%; p&amp;lt;0.001) and in HFmrEF (22.2% vs. 18.09%; p=0.029), but not for HFpEF (23.9% vs. 23.3%; p=NS). In the multivariate analysis, adjusted for age, sex, previous myocardial infarction and stroke, diabetes, CKD, PAF, Cardiac surgery, and electronic device implantation, PAF was an independent predictor of death in all HF phenotypes: HFrEF [HR=1.78(95%CI:1.57-2.02); p&amp;lt;0.001], HFmrEF [HR=2.14(95%CI:1.74-2.65); p&amp;lt;0.001], HFpEF [HR=2.08(95%CI:1.82-2.37); p&amp;lt;0.001]. Conclusion PAF is a frequent comorbidity in HF and is associated with a worse prognosis in all HF phenotypes. Women with PAF had a better prognosis than men with AF in HFrEF and HFmrEF. Sex-specific strategies to maintain sinus rhythm in HF patients on the overall risk of death are needed.

Effects of dapagliflozin in heart failure according to duration of type 2 diabetes: a patient-level meta-analysis of DAPA-HF and DELIVER

Abstract Introduction Type 2 diabetes (T2D) is a common comorbidity in heart failure (HF), and long-standing T2D is associated with worse outcomes. Purpose To investigate the efficacy and safety of dapagliflozin, compared with placebo, according to duration of T2D in patients with HF and established T2D. Methods We conducted a patient-level pooled analysis of the DAPA-HF and DELIVER trials, which evaluated the effects of dapagliflozin, compared with placebo, in patients with HF with reduced ejection fraction and HF with mildly reduced/preserved ejection fraction, respectively. T2D duration was categorized as &amp;lt;5 years, 6-10 years, and &amp;gt;11 years. The primary outcome was a composite of worsening HF or cardiovascular death. Results Of the 4,784 patients with a history of T2D, 1,879 (39.3%) had a T2D duration of &amp;lt;5 years, 1,074 (22.4%) 5-10 years, and 1,831 (38.3%) &amp;gt;11 years. Patients with longer-duration T2D were older, more often female, and White, and had a higher HbA1c, body mass index, and left ventricular ejection fraction. They were more likely to have ischaemic heart disease, peripheral artery disease, hypertension, and chronic kidney disease, but were less likely to have atrial fibrillation/flutter. Although patients with longer-duration T2D had longer duration of HF, they were not more likely to have a prior HF hospitalization or worse New York Heart Association functional class. Despite similar N-terminal pro-B-type natriuretic peptide levels, patients with longer-duration T2D had a higher risk of the primary outcome, even after adjustment for potential confounders (&amp;lt;5 years, reference; 6-10 years, HR 1.25 [95% CI, 1.06-1.46]; &amp;gt;11 years, HR 1.33 [1.15-1.54]). The benefit of dapagliflozin on the primary outcome was consistent across T2D duration category: &amp;lt;5 years, HR 0.85 (95% CI, 0.69-1.04); 5-10 years, HR 0.65 (0.51-0.83); &amp;gt;11 years, HR 0.84 (0.70-1.01) (Pinteraction=0.18). Dapagliflozin reduced the risk of secondary clinical outcomes and increased (improved) mean KCCQ scores from baseline to 8 months, regardless of T2D duration (Table). Adverse events and treatment discontinuation were not more frequent with dapagliflozin than with placebo irrespective of T2D duration. Conclusions Dapagliflozin reduced the risk of worsening HF or cardiovascular death, and improved symptoms, in patients with HF and T2D, irrespective of T2D duration.

Transferrin saturation is a superior prognostic biomarker for iron deficiency after acute decompensated heart failure: a retrospective clinical real-world cohort study

Abstract Background Iron deficiency (ID) is the most common extracardiac comorbidity in heart failure (HF) and associated with worse outcomes. While a uniform definition of ID in HF remains lacking, several biomarkers for ID, including ferritin and transferrin saturation (TSAT), are used in both clinical trials and clinical practice. However, which biomarker is a superior prognostic predictor for ID in HF remains unsettled. In addition, real-world clinical data on ID screening and intravenous (IV) iron treatment is largely missing. Purpose To determine which biomarker is a superior prognostic predictor for the composite endpoint of HF rehospitalisation (HHF) and all-cause mortality in a real-world cohort of patients with HF and coexisting ID, and to investigate frequency and predictors of ID screening and IV iron treatment. Methods In this retrospective cohort study, all patients aged 18-85 years hospitalised at a tertiary university hospital with new onset HF with reduced ejection fraction (HFrEF) in 2016-2020 were consecutively included from medical records by ICD-10 code I50.0-I50.9 and followed until 31 December 2021. Patient characteristics, comorbidities, medications, laboratory results and data on follow-up, including if ID was tested for, IV iron administration, HHF and all-cause mortality was collected. First available iron status after admission for index hospitalisation was used. Predictors for ID screening and IV iron use were identified with univariate logistic regression. The association between ID markers and the composite endpoint was analysed with Cox regression adjusted for age, sex, baseline anemia, estimated glomerular filtration rate (eGFR) &amp;lt;30 mL/min/1.73 m2 and N-terminal pro-B type natriuretic peptide (NT-proBNP) below median value with median ferritin and TSAT values set as references respectively. Results In all, 753 patients were included (66.5 ± 12.7 years, 508 (67.5%) men, ejection fraction 29.5 ± 6.9% and mean NT-proBNP 6241 ± 7183 ng/L). Of these, 484 (64.3%) were screened for ID and 235 (48.6%) fulfilled criteria for ID. Of these, 94 (40.0%) received IV iron. Of screened patients, 28.6% had ID with anemia and 20.8% ID without anemia (Table 1). Factors associated with screening for ID were follow-up at hospital, anemia, eGFR &amp;lt;30 mL/min/1.73 m2 and ischemic heart disease, and for IV iron additionally chronic kidney disease and peripheral artery disease. Median ferritin was 140 µg/L and TSAT 0.2. Both ferritin and TSAT displayed an inversely linear association with outcomes, while TSAT &amp;lt;0.2 showed a stronger association with increased risk of HHF and all-cause mortality compared to median values (Figure 1-2). Conclusions In a real-world clinical setting, TSAT was a superior prognostic biomarker for worse outcomes compared to ferritin in patients hospitalised for acute HF. While both ID screening and IV iron use remained greatly underutilised in clinical practice, identification of a reliable biomarker for ID is critical.

Effect of baseline and one-year follow-up anemia status on long-term clinical outcomes in patients with heart failure

Abstract Background Anemia is a significant comorbidity in heart failure (HF), influencing patient prognosis and quality of life. In patients with HF, fluctuations in anemia status can markedly impact long-term outcomes. Purpose The aim of this study was to evaluate the long-term prognosis of HF patients according to change in anemia status at the baseline and one-year follow-up. Methods Data were obtained from a multicenter cohort of patients hospitalized for acute heart failure (AHF) from 10 tertiary university hospitals between March 2011 to February 2014. Out of 5,625 AHF patients, the study population was consisted of 1,798 patients with available data on hemoglobin levels at baseline and one-year follow-up. Anemia is defined as hemoglobin levels below 13 g/dL for men and 12 g/dL for women. These patients were then categorized into four groups: group ‘anemia to anemia’; group 2 ‘no-anemia to anemia’; group 3 ‘anemia to no-anemia’; group4 ‘no-anemia to no-anemia’. Primary outcome was the composite incidence of cardiac death or HF readmission. Results Among 1,798 patients, 718 patients (39.9%) died during follow-up (mean 1169.1 ± 880.7 days, median 1057.5 days) and 816 patients (45.4%) developed primary outcome. The patients with baseline anemia had a worse clinical profile than those without anemia. The development of primary outcome tended to significantly decrease from group 1 to group 4 (55.6% vs. 48.1% vs. 40.2% vs. 36.3%, p for trend &amp;lt;0.001). In addition, the incidence of all-cause death, cardiac death, readmission due to cardiac cause, and HF readmission also tended to decrease significantly toward group 4. The cumulative cardiac death or HF readmission free survival rate showed significantly lowest in the group 1 (log-rank p-value &amp;lt; 0.001), and the survival rate increased from Group 1 to Group 4 (Figure). After adjusting for confounding factors, Cox regression analysis showed that anemia to anemia group was independently associated with a 1.368-fold increased risk of primary outcome compared to no-anemia to no-anemia group during follow-up (Hazard ratio [HR] 1.368, 95% confidence interval [CI] 1.110-1.701, p = 0.005). No-anemia to anemia group had also a 1.376-fold increased risk of primary outcome (HR 1.376, 95% CI 1.043-1.814, p = 0.024) compared with no-anemia to no-anemia group. Conclusions In conclusion, the risk of adverse clinical outcomes including cardiac death and HF readmission increased progressively in groups transitioning from no-anemia to anemia or consistently remaining anemic in AHF patients. Conversely, those who improved from anemia to non-anemia or remained non-anemic exhibited a decreased risk, highlighting the critical role of anemia status as a determinant of long-term prognosis. Clinicians should actively manage and monitor anemia as an essential component of treatment strategies to improve long-term outcomes in patients with HF.Kaplan-Meier Survival curve

Anemia and 4 cavities myocardial strain in acute heart failure

Abstract Background Anemia is a frequent comorbidity in heart failure (HF) in elderly patients. Few data are available concerning the correlation between anemia and echocardiographic morphologic, functional and hemodynamic markers in acute HF. Purpose The aim of the study was to evaluate 4 cavities myocardial strain in elderly patients hospitalized with acute HF and to evaluate the influence of the presence of concomitant anemia. Methods One hundred and seven patients aged 70 years or older, hospitalized for acute HF were prospectively analyzed. Left ventricle longitudinal strain (LVGLS), left atrial (LA) reservoir, right atrial (RA) reservoir and right ventricle (RV) free wall strain were measured using speckle tracking transthoracic echocardiography (TTE) at admission. The population was divided into 2 groups, with (N = 47) or without (N = 60) of anemia. Results Mean age was 81.2 ± 6.6 years; 67 (62.6%) patients were men. Anemia was documented in 60 (56.1%) patients. Patients with anemia, compared to those without anemia, had more frequently history of hypertension, diabetes, renal insufficiency, and iron deficiency (Table 1). Patients with anemia, compared to those without anemia, had higher indexed cardiac output, LV ejection fraction and tricuspid annular plane systolic excursion, TAPSE (Table 1). Myocardial strain analysis found that patients with anemia, compared to those without anemia, had significantly higher LVGLS, LA and RA reservoir strain (Figure 1). Conclusion Anemia is common in elderly patients with decompensated HF. Patients suffering from both anemia and acute HF exhibited significantly higher myocardial strain (except free wall RV strain), suggesting a possible compensatory mechanism. Further investigations are necessary to understand the pathophysiologic links between HF, anemia and myocardial strain as well as their implications for prognosis.

BA6b9, a novel sk4 K + channel blocker, attenuates atrial fibrillation substrate in rats with reduced ejection fraction

Abstract Background Atrial fibrillation (AF), the most common cardiac arrhythmia, is strongly associated with several comorbidities including heart failure (HF). AF in general, and specifically in the context of HF, is progressive in nature and associated with poor clinical outcomes. Current therapies for AF are limited in number and efficacy and do not target the underlying causes of atrial remodeling such as inflammation or fibrosis. We previously identified the calcium-activated SK4 K+ channels, which are preferentially expressed in the atria relative to the ventricles in both rat and human hearts, as novel druggable targets for efforts to treat AF. Methods and Findings We examined the ability of BA6b9, a novel allosteric inhibitor of SK4 channels that targets the specific calmodulin-PIP2 binding domain, to alter AF susceptibility and atrial remodeling in a systolic HF rat post-myocardial infarction (post-MI) model. Daily BA6b9 injection (20 mg/kg/day) for 3 weeks starting 1-week post-MI prolonged the atrial effective refractory period, reduced AF induction and duration, and dramatically prevented atrial structural remodeling. In the post-MI left atrium (LA), pronounced upregulation of the SK4 K+ channel was observed, with corresponding increases in collagen deposition, α-SMA levels, and NLRP3 inflammasome expression. Strikingly, BA6b9 treatment reversed these changes while also significantly reducing the lateralization of the atrial connexin Cx43 in the LA of post-MI rats. Interpretation Our findings indicate that the blockade of SK4 K+ channels using BA6b9 not only favors rhythm control but also remarkably reduces atrial structural remodeling, a property that is highly desirable for novel AF therapies, particularly in patients with comorbid HF.

Impact of semaglutide on weight and functional outcomes among obese heart failure patients: a propensity scores matching analysis

Background & objectivesObesity is a common comorbidity in heart failure, yet effective pharmacological options for weight loss in these patients are limited. Semaglutide, a glucagon-like peptide 1 receptor agonist, has shown promise for weight reduction in obese adults. This study aims to evaluate semaglutide’s impact on weight loss, functional status, and clinical outcomes in obese patients with heart failure.MethodsA retrospective analysis was conducted on all consecutive obese (BMI > 30 kg/m²) patients with heart failure at the University Hospital Bonn outpatient clinic from July 2019 to July 2022. Propensity score matching paired patients receiving semaglutide as an add-on therapy (SEMA) with those on medical therapy alone (Control).ResultsAmong 1,942 patients with heart failure screened, 26 matched pairs were identified. At one year, the SEMA group exhibited significant weight loss, with a mean BMI reduction of -2.91 kg/m² (95% CI: -4.27 to -1.55; p < 0.001), while the control group showed a non-significant mean change of -0.41 kg/m² (95% CI: -1.08 to 0.26; p = 0.22). The difference in BMI between the two groups was statistically significant (mean difference: 3.42 kg/m², 95% CI: 1.43 to 5.42; p = 0.001). Improvements by at least one NYHA class were observed in 65% of the SEMA group (p < 0.001) compared to 15% of the control group (p = 0.18). The SEMA group also showed a significant increase in 6-minute walk distance (6MWD), with a mean difference of 75 m between the groups at one year (95% CI: 0.53 to 150.02; p = 0.049). NT-proBNP levels significantly decreased in the SEMA group (p < 0.001) compared to the control group (p = 0.78), with a statistically significant difference in NT-proBNP between the groups (p = 0.048). Both improvements in 6MWD and reductions in NT-proBNP were significantly correlated with BMI percentage reductions.ConclusionsSemaglutide was associated with significant weight reduction in obese patients with heart failure, accompanied by improved NYHA classification and 6-minute walk distance. Larger, multi-center trials and prospective, randomized controlled trials are warranted. These studies should focus on assessing long-term outcomes, optimizing dosage, and exploring the potential cardiovascular benefits beyond weight reduction.

Impact of diabetes mellitus on right ventricular dysfunction and ventricular interdependence in hypertensive patients with heart failure with reduced ejection fraction assessed via 3.0 T cardiac MRI

BackgroundHypertension (HTN) and diabetes mellitus (DM) are two common comorbidities of heart failure with reduced ejection fraction (HFrEF), each of which can cause right ventricular (RV) dysfunction. The aim of this study was to investigate the impact of DM on RV dysfunction and ventricular interdependence in hypertensive HFrEF patients via cardiac magnetic resonance imaging (MRI) feature tracking.MethodsThis study included 249 patients with HFrEF: 77 HFrEF controls, 97 with hypertensive HFrEF (HTN-HFrEF [DM-]) and 75 with hypertensive HFrEF and comorbid DM (HTN-HFrEF [DM+]). The cardiac MRI-derived biventricular global radial (GRS), circumferential (GCS) and longitudinal (GLS) peak strains were obtained and compared among the groups. Multivariable linear regression and mediation analyses were used to evaluate the effects of DM and left ventricular (LV) strain on RV strain.ResultsThe biventricular GLS and GLS of segments 8, 9 and 14 of the interventricular septum (IVS) decreased gradually from the HFrEF control group to the HTN-HFrEF (DM−) group to the HTN-HFrEF (DM+) group (all P < 0.05). Patients with DM had even lower biventricular GCS and IVS strains in all directions in specific segments than did those without DM and the HFrEF controls (all P < 0.05). DM was independently associated with impaired RVGLS and RVGCS (both P < 0.05) in hypertensive HFrEF patients. The difference in RVGLS between the hypertensive HFrEF subgroups was partly mediated by LVGLS [β = 0.80, 95% CI (0.39–1.31)], and that of RVGCS was partly mediated by LVGCS [β = 0.28, 95% CI (0.01–0.62)].ConclusionsIn hypertensive HFrEF patients, comorbid DM may have aggravated RV dysfunction and was an independent determinant of impaired RV strain. RV dysfunction might be directly affected by DM and partially mediated by LV strain through unfavorable ventricular independence.