bluuebunny/crossref_metadata_2025_split huggingface dataset:
Up-titration of Guideline Directed Medical Therapy (GDMT) and the occurrence of side effects in Heart Failure with reduced Ejection Fraction (HFrEF)
Authors: Panagiotides N , Weidenhammer A , Arfsten H , Prausmueller S , Spinka G , Bartko P , Goliasch G , Huelsmann M , Pavo N 
Published: October 2024

Abstract

Background
The ESC Guidelines recommend early, full-dose use of heart failure (HF) medications to enhance survival, but real-world application often faces delays and inconsistencies. Clinicians often fear side effects during up-titration to the recommended target dose (TD), i.e. hypotension, bradycardia, renal impairment, and hyperkalemia (HK). The dependency of side effects during dose escalation from the severity of HF remains unclear.

Purpose
This study aimed to evaluate the relationship between the occurrence of side effects during up-titration of HF medication and HF severity reflected by N-terminal pro B-type natriuretic peptide (NT-proBNP).

Methods
425 patients with HFrEF and a complete data set of patient characteristics, medications and laboratory values at baseline (BL), 2 months (2M), and 6 months (6M) were included from our outpatient HF unit's prospective registry. Significant side effects were defined as: systolic blood pressure (SBP) &lt;90mmHg, heart rate (HR) &lt;50 beats per minute (bpm), potassium (K) &gt;5.0mmol/l or K &gt;5,5mmol/l and estimated glomerular filtration rate (eGFR) &lt;30ml/min/1.73m2. Patients were categorized into three risk groups based on their NT-proBNP levels, i.e. low-risk with NT-proBNP &lt;1000pg/ml, medium-risk with NT-proBNP 1000-2000pg/ml or high-risk with NT-proBNP &gt;2000pg/ml. The occurrence of side effects was recorded and the development compared among the HF risk groups.

Results
Figure 1 shows up-titration of HF medication. Mean daily dosages of betablockers (BB), mineralocorticoid receptor antagonists (MRA) and renin-angiotensin-system inhibitors (RASi) increased significantly during follow-up (BL vs 2M and BL vs 6M, p&lt;0.001 for all). The majority of patients received ≥50% of the recommended TDs at 6M (89% for BB, 83% for MRA, 88% for RASi and 91% for total mean TDs ≥50%), and the achieved daily dosages at 6M were largely comparable across the HF risk groups at 6M, except for RASi (p=0.030).
Figure 2 depicts the side effects. Side effects developed almost exclusively at short-term within 2M except for lower SBP (Figure 2A). Newly developed side effects occurring after up-titration (2B) were even more rare and predominantly occurred within the highest NT-proBNP group. The occurrence of hypotension and bradycardia was infrequent and comparable within the HF risk groups. Renal dysfunction (at 6M p=0,041) and HK occurred predominantly in higher risk patients (HK at 2M p=0,001 and at 6M p&lt;0,001).

Conclusions
Up-titration of HF medications is highly feasible, particularly in low- and medium-risk patients. Despite rare side effects such as hyperkalemia and renal impairment, up-titration remains unimpeded, especially in patients with NT-proBNP levels below 2000pg/ml. These findings emphasize the safety of up-titration in HF.
Prognostic role of right ventricular-pulmonary artery coupling assessed by TAPSE/PASP ratio in patients with heart failure and mildly reduced ejection fraction
Authors: Ono M , Suzuki A , Yoshida A , Minami Y , Kikuchi N , Hattori H , Shiga T , Ashihara K , Yamaguchi J 
Published: October 2024

Abstract

Background
The development of right ventricular (RV)-pulmonary arterial (PA) coupling has resulted in a novel and comprehensive index for evaluating RV function in relation to the underlying RV afterload. In patients with heart failure (HF), it is acknowledged that RV-PA uncoupling are features that are associated with poor outcome. The RV-PA coupling index can be readily assessed non-invasively using the ratio of two standard echocardiographic measurements: tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP). However, few studies have defined the prognostic impact of the TAPSE/PASP ratio in patients with HF and mildly reduced EF (HFmrEF).

Methods
From the prospective cohort study of 1,410 hospitalized HF patients (age 68+/-15, men 62%) between August 2015 and September 2019, this study enrolled 191 HFmrEF (i.e., left ventricular ejection fraction (LVEF) 41–49%) patients whose TAPSE and PASP were measured during hospitalization and discharged alive. We studied the prognostic impact of TAPSE/PASP ratio on HFmrEF patients using by cut-off value obtained from receiver operating characteristic (ROC) analysis. The primary and secondary endpoints was defined as the all-cause death and HF re-hospitalization after discharge, respectively.

Results
During median follow-up of 38 [23–52] months, 48 patients (25%) died. The deceased patients had a significantly older (median 75 vs. 71 years, p&lt;0.05), higher rate of ischemic heart disease (50% vs. 23%, p&lt;0.05), elevated brain natriuretic peptide levels (325 vs. 159 pg/ml, p&lt;0.05) and lower rate of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (65% vs. 80%, p&lt;0.05) at discharge. In the ROC analysis, the cut-off value of TAPSE/PASP ratio for mortality was 0.46. Patients with TAPSE/PASP ≤0.46 had a significantly higher all-cause mortality (log-rank p&lt;0.05) and had a tendency of higher rate of HF re-hospitalization than patients with TAPSE/PASP &gt;0.46 (log-rank p=0.06) (Figure). Using multivariate analysis, the lower TAPSE/PASP ratio had an independent predictive value of prognosis in patients with HFmrEF (hazard ratio 2.16, 95% confidence interval; 1.08–3.92, p&lt;0.05) (Table).

Conclusion
The TAPSE/PASP ratio has a significant prognostic value in patients with HFmrEF. The RV-PA uncoupling assessed by TAPSE/PASP ratio might be useful for risk assessment in patients with HFmrEF.
Impact of various iron deficiency definitions on mortality risk in chronic heart failure across the spectrum of left ventricular ejection fraction spectrum
Authors: Mohamed A , Daniel Moelager Christensen D M C , Milan Mohammad M M , Christian Torp-Pedersen C T P , Lars Koeber L K , Emil Loldrup Fosboel E L F , Tor Biering-Soerensen T B S , Morten Lock M L , Mariam Elmegaard Malik M E M , Nina Nouhravesh N N , Charlotte Anderrson C A , Morten Schou M S , Gunnar Gislason G G 
Published: October 2024

Abstract

Introduction
Iron deficiency (ID) is prevalent in chronic heart failure (HF) but lacks a consensus definition.

Purpose
This study evaluates the prevalence of ID and its association with all-cause mortality and first hospitalization for HF, using current European Society of Cardiology (ESC) guidelines, transferrin saturation (TSAT) &lt;20%, ferritin &lt;100 ng/ml, and serum iron ≤13 μmol/L as ID criteria.

Methods and Results
Of 8587 new-onset HF patients registered in the Danish Heart Failure Registry from April 2003 to July 2021, we found varying ID prevalence (35.4% to 67%) based on different definitions. In heart failure with reduced ejection fraction (HFrEF) patients, irrespective of anemia, ID defined by TSAT &lt;20% and serum iron ≤13 μmol/L was associated with all-cause mortality (non-anemic, HR: 1.42, 95% CI:1.22-1.64 and HR: 1.25, 95% CI: 1.1-1.43; anemic, HR: 1.22, 95% CI: 1.1-1.35 and HR: 1.26, 95% CI: 1.12-1.41, respectively) and first HF hospitalization (non-anemic, HR:1.41, 95% CI:1.23-1.62, HR: 1.33, 95% CI: 1.18-1.51; anemic, HR:1.27, 95% CI:1.12-1.45 and HR: 1.26, 95% CI:1.09-1.45, respectively). ID per ESC guidelines was only associated to mortality in non-anemic HFrEF (HR: 1.24, 95% CI:1.09-1.42) and first HF hospitalization in HFrEF, irrespective of anemia (non- anemic, HR:1.24, 95% CI:1.09-1.42; anemic, HR:1.35, 95% CI:1.2-1.52). No association was observed between the various definitions and outcomes in patients with heart failure with mildly reduced ejection fraction and heart failure with preserved ejection fraction.

Conclusion
ID, when defined by TSAT &lt;20% or serum iron ≤13 μmol/L, is associated with increased mortality and first hospitalization in HFrEF patients, regardless of anemia. Conversely, ID as per ESC guidelines is associated with mortality in non-anemic HFrEF patients and first hospitalization in HFrEF, irrespective of anemia status.Figure 1:Forest plot mortalityFigure 2:Forest plot hospitalization
Obesity paradox exists in super elderly patients with heart failure
Authors: Tachibana T , Kubota Y , Nishino T , Kato K , Iwade Y , Hayashi D , Watanabe Y , Matsuda J , Miyachi H , Tara S , Tokita Y , Iwasaki Y , Asai K 
Published: October 2024

Abstract

Background
Aging and obesity are two global concerns in public health. As obesity is associated with several metabolic disorders, it is a well-known risk factor of heart failure (HF). However, several studies have suggested that obesity may have paradoxical survival benefits in patients with HF. Therefore, the aim of this study was to investigate whether the obesity paradox exists in super elderly patients with HF in Japan.

Methods
A total of 4,292 patients from our hospital HF registry were divided into four age subgroups: (A) less than 65, (B) elderly 65-74, (C) high elderly 75-84, (D) super elderly ≥85. The primary endpoint was the all-cause death within 1-year after discharge.

Results
At baseline, the proportion of men in each group was 42-76%, the mean left ventricular ejection fraction was 49-61%, the average of N-terminal pro-B-type natriuretic peptide was 1972-2944 pg/ml, and the mean body mass index (BMI) ranged 21-25 kg/m2. Patients with higher BMI were more common in the younger age group, while those with lower BMI were more common in the older age group. Cubic spline curves of Cox proportional hazard regression models demonstrated an inverse relationship between BMI and mortality (Fig. 1). Lower BMI was associated with higher all-cause mortality in all ages, although this association was attenuated at the young age, and pre-obesity (25–29.9 kg/m2) was associated with the greatest survival benefit. Meanwhile, the impact of underweight (&lt;18.5 kg/m2) was stronger super elderly subjects, a one-unit increase in BMI was associated with a 10.3% decrease in the hazard ratio of death (P=0.021). Kaplan-Meier curves for all-cause mortality also showed that lower BMI was associated with higher all-cause mortality in all groups, and the differences were statistically significant in Groups B, C, and D (Fig. 2).

Conclusion
Our study suggested the existence of the obesity paradox among HF patients in super elderly. Mildly overweight may be beneficial at old age with HF.
Clinical outcomes of patients with heart failure with improved ejection fraction after acute MI: a multicenter prospective study from the COREA-AMI Registry
Authors: Seung J , Kim J J , Kim Y R , Hwang B Y , Chang K Y 
Published: October 2024

Abstract

Background
The 2021 Universal Definition of Heart Failure introduce a new classification, heart failure with improved ejection fraction (HFimpEF). As yet, little is known about the long-term clinical outcomes of patients with HFimpEF after acute myocardial infarction (AMI).

Methods
From a multicenter, prospective cohort of AMI patients undergoing PCI, patients with an initial echocardiogram at the time of PCI and at least one follow-up echocardiogram one month to two years after the initial event were considered for analysis. HFimpEF was defined as initial left ventricular ejection fraction (LVEF)≤40% and at least one follow-up LVEF&gt;40% with an increase of ≥10% from baseline. Persistent HFrEF was defined as LVEF ≤40% without interval improvement. Patients with LVEF&gt;40% were defined as having preserved LVEF. The primary endpoint was all-cause mortality.

Results
In total, 3038 patients with repeated echocardiogram measurements were selected for initial analysis. 187 patients were identified as having HFimpEF, 190 patients had persistent HFrEF, 631 patients had HFmrEF, and 2030 patients had preserved EF. Kaplan-Meier analysis revealed that HFimpEF was associated with improved survival compared to chronic HFrEF, but inferior to preserved LVEF (log-rank p&lt;0.001). Even after multivariate Cox regression analysis was done to account for confounding variables, HFimpEF was associated with reduced mortality compared to persistent HFrEF (HR 0.49, 95% CI 0.31-0.78). Compared to patients with preserved LVEF, HFimpEF patients had a tendency toward higher mortality, but did not reach statistical significance (HR 1.18, 95% CI 0.80-1.76).

Conclusion
HFimpEF is associated with decreased all-cause mortality compared to persistent HFrEF in patients with AMI.
Multiple comorbidities are associated with poor prognosis in patients with ADHF-HFpEF and non-frailty or mild frailty but not moderate-severe frailty -PURSUIT-HFpEF Registry-
Authors: Kondo T , Watanabe T , Yamada T , Seo M , Yano M , Hayashi T , Nakagawa A , Nakagawa Y , Yasumura Y , Sotomi Y , Okada K , Hikoso S , Nakatani D , Fukunami M , Sakata Y 
Published: October 2024

Abstract

Background
A variety of comorbidities are frequently observed and represent a major problem in the management of patients with heart failure. Frailty is a strong predictor of poor clinical outcome in patients with heart failure, which may be partially attributable to the presence of multiple comorbidities. However, it remains to be clarified whether frailty is prognostically useful in relation to multiple comorbidities in patients with acute decompensated heart failure and preserved ejection fraction (ADHF-HFpEF).

Purpose
The purpose of this study is to investigate the relationship between frailty, multiple comorbidities and prognosis in patients with ADHF-HFpEF.

Methods
We prospectively studied 1028 patients with ADHF-HFpEF. Frailty was assessed using Clinical Frailty Scale (CFS). Multiple comorbidities were defined as the presence of 4 or more factors from the following 11 groups: diabetes, obesity, lung disease, anemia, renal dysfunction, electrolyte disorder, dyslipidemia, depression, hypertension, stroke and cancer. The primary outcome of this study was the composite endpoint of all-cause mortality and rehospitalization for worsening heart failure.

Results
During a mean follow-up period of 1.6±1.3 years, 454 patients underwent primary outcome. CFS (p&lt;0.001) and the number of comorbidities (p=0.006) were significantly independently associated with primary outcome after multivariate adjustment. Kaplan-Meier analysis revealed that patients with multiple comorbidities had significantly higher risk for primary outcome than those without multiple comorbidities in the group with non-frailty (defined as CFS of 1 or 2, p=0.019) and mild frailty (CFS of 3 or 4, p=0.036). However, there was no significant difference in the group with moderate or greater frailty (CFS of 5 or more) in patients with ADHF-HFpEF.

Conclusion(s)
Multiple comorbidities would be associated with poor prognosis in patients with ADHF-HFpEF and non-frailty or mild frailty but not in patients with moderate or greater frailty.Multiple comorbidities and MACE risk
Global and national insights into the decline of hypertrophic cardiomyopathy as a cause of sudden death in the young
Authors: Nelson D , Rowe S , Ha F , Lim H , Playford D , Strange G , Ellims A , Semsarian C , La Gerche A , Paratz E 
Published: October 2024

Abstract

Background & Objective
Hypertrophic cardiomyopathy (HCM) has been reported as a leading cause of sudden cardiac death (SCD) in the young but appears less common in contemporary cohorts of young SCD. This research aimed to determine if HCM is a common cause of SCD in the young and whether this has changed over time.

Methods
We analysed three national databases, the National Echo Database Australia (NEDA), Centre for Disease Control Wide-ranging Online Data for Epidemiologic Research (CDC-WONDER) and the National Coronial Information System of Australia (NCIS) to determine incidence of SCD due to HCM in ≤ 35 years old from 1999-2017. Sub-analyses assessed for differences in sex and obstructive and non-obstructive HCM phenotypes.

Results
NEDA: Of 40,738 individual echocardiograms 2005-2017, 868 (2.13%) exhibited the HCM phenotype. 982 patients died ≤ 35 years, of which 4 deaths were attributable to HCM (0.4%). CDC-WONDER: 41% reduction in HCM related mortality/million people across 1999-2016 (p&lt;.0001). Similar reduction was seen when stratified for age, sex and non-obstructive/obstructive HCM phenotype. NCIS: 36% reduction in HCM-related SCD was observed between 2001-2010 and 2011-2016 periods (p=.049).

Conclusions
HCM rarely causes SCD and accounts for &lt;5% of SCD in the young. Rates of HCM-related SCD have been decreasing over the last two decades. Improved survival likely relates to improved case detection and medical management.Abstract Figure
Masked hypotension in patients with heart failure
Authors: Li Z , Qiu Z E P I N G , Jin W E I 
Published: October 2024

Abstract

Background
Hypotension limits the up-titration of guideline-directed medical therapies (GDMTs) and correlates with poor prognosis in patients with heart failure. The value of ambulatory blood pressure monitoring (ABPM) in heart failure patients and its association with GDMTs optimization and clinical outcomes were undetermined.

Methods
REM-HF (Risk Evaluation and Management in Heart Failure) is a multicenter, prospective observational cohort. Our study screened patients from REM-HF who were hospitalized for incident HF and newly initiated GDMTs between April 2018 and December 2022. Eligible participants conducted a 24-hour ABPM before discharge and were followed-up as the cohort routine. GDMTs target dose achievement and dose trajectories were assessed at 3-month visit. The primary outcome was a composite of all-cause mortality and heart failure readmission.

Results
On adjusted restricted cubic spline analysis, office SBP demonstrated a U-shape relationship with the primary outcome (P for nonlinearity=0.003), while 24-hour SBP was linear (P for nonlinearity=0.338). The risk-related threshold of ambulatory and office systolic hypotension was defined as corresponding SBP &lt; 120 mmHg accordingly. Combining these two measurements together, we described three blood pressure status as sustained hypotension (s-hypo, both SBP &lt; 120 mmHg), masked hypotension (m-hypo, 24h SBP &lt; 120 mmHg while office SBP ≥ 120mmHg), and non-hypotension (n-hypo). Among the 491 patients included, 124 (25.3%), 151 (30.8%) and 216 (44.0%) had s-hypo, m-hypo, and n-hypo, respectively. The m-hypo group showed similar clinical features as the s-hypo subjects, including more serious left ventricle remodeling and worse cardiac function. After the GDMTs dose titration, either patients with s-hypo or m-hypo were as unlikely to achieve target dose as the non-hypotensives (OR for s-hypo 0.42, 95%CI 0.19-0.95, P=0.038; OR for m-hypo 0.39, 95%CI 0.19-0.80, P=0.011). During a median follow-up of 693 days, the adjusted risk of primary outcome was higher in the s-hypo group and m-hypo group compared with the non-hypo group (HR for s-hypo 2.47, 95%CI 1.54-3.96, P&lt;0.001; HR for m-hypo 1.68, 95%CI 1.06-2.65, P=0.027). No significant differences were found in target dose achievement and clinical outcomes between the s-hypo and m-hypo groups.

Conclusion
Masked systolic hypotension can occur in nearly one-third of new-onset HF patients. Patients with m-hypo and s-hypo exhibit similar clinical characteristics, both associated with GDMTs intolerance and adverse outcomes, suggesting m-hypo deserves recognition as a discrete entity. ABPM provides a more comprehensive view of patients’ blood pressure status by identifying this population.
Prevalence and outcomes of American Heart Association stages of heart failure in an adult brazilian population of the ELSA-Brasil study
Authors: Pianca E G , Heidemann Junior A , Santos A B S , Bittencourt M S , Ribeiro A L P , Lotufo P A , Duncan B B , Foppa M 
Published: October 2024

Abstract

Aims
Heart failure (HF) has a major impact on public health, affecting up to 2% of adult population. HF staging is helpful in capturing pre-clinical disease and its progression to advanced stages. We aimed to determine the prevalence and mortality of HF stages in the participants of a Brazilian adult cohort.

Methods
The ELSA-Brasil cohort comprises 15,105 adult public servants from 6 Brazilian capitals. In the initial evaluation of the study (2008-2010), ELSA carried out interviews and clinical, laboratory, and cardiovascular ancillary tests. In this analysis, we included participants who had electrocardiogram and echocardiogram performed at baseline visit, and additional information regarding risk factors and functional capacity.
The HF stages were defined based on AHA guidelines criteria as follow: Stage 0 was defined as a healthy individual with no risk factors for heart failure. Stage A (at risk for HF) included those without cardiac structural or functional abnormality but with any of the following conditions: systemic hypertension; diabetes mellitus, obesity, history of myocardial revascularization, history of rheumatic fever, and seropositivity for Chagas’ disease. Stage B (pre-HF) was defined as asymptomatic participants with history of myocardial infarction or any major abnormalities on ECG or echocardiogram. Stage C (symptomatic HF) included participants with a clinical history of HF, or HF symptoms in the presence of structural heart disease (defined as in Pre-HF stage). Considering the community-dwelling profile of the sample, we did not expect to have advanced heart failure patients in our sample.

Results
We included the 3,267 participants (61±9 years; 53% women) with baseline data. Prevalences of HF stages were stage 0: 938 (29%) A: 1,385 (42%), B: 651 (28%) and C: 293 (9%), with different distribution between sexes (p&lt;0.001). Older participants had higher prevalences of stages B and C (p&lt;0.001), with the prevalence of stage C increasing from 1.8% at 35-44 years to 12.2% at 65-74 years. After 12 years of follow-up, total mortality rates of HF stages were Stage 0: 4%; A:10%. B: 16%, and C: 26%, and respective Cox proportional hazard ratios [95% CI] adjusted for age and sex were A: 1.94 [1.3-2.8], B:2.78 [1.9-4.1], and C: 5.39 [3.6-8.1] compared to stage 0.

Conclusions
The prevalence of HF in Brazilians reflects what is described in international literature, with a large proportion of individuals in pre-symptomatic stages. A notable shift in the sample toward pre-symptomatic and symptomatic HF occurred gradually and persistently across the age span studied. Mortality rates increase incrementally across the HF stages. This information is important for understanding and planning health policies for this syndrome.