bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obesity plays a key role in inducing myocardial and vascular dysfunction in a translational model of heart failure with preserved ejection fraction in rats
Authors: Simoes M , Oliveira-Neto P , Sapalo A T , Tanaka D M , Carvalho E E V , Rodrigues K P , Souza H C D , Tostes R , Fazan R , Romano M M 
Published: October 2024

Abstract

Background
Exploring experimental models of heart failure with preserved ejection fraction (HFpEF) may help to understand the mechanisms leading to this challenging condition.

Purpose
In a translational model, we aimed to assess the relative contribution of hypertension and obesity in inducing structural, functional and hemodynamic changes associated to the HFpEF phenotype.

Methods
We investigated 3 groups of male 40 weeks old rats: control Wistar Kyoto (WKY, n=10), Spontaneous Hypertensive Rats (SHR, n=10) and SHR with obesity induced by consumption of cafeteria diet during 28 weeks (Ob-SHR, n=9). Animals were submitted to assessment of: body weight, systolic (SBP) and diastolic (DBP) blood pressure; in vivo structural and functional changes evaluated by high resolution Echocardiography including left atrial dimension (LA), left ventricle (LV) diastolic dimension (LVDD), LV posterior wall thickness (LVPW), LV wall relative thickness (LVWRT), LV ejection fraction (LVEF). Invasive hemodynamic evaluation assessed the intraventricular pressure curves obtaining LV end diastolic pressure (LVEDP) and calculation of LV diastolic time constant (Tau). After euthanasia, thoracic aorta was used for vascular function assessment by measuring the maximal cumulative concentration-effect curves of contraction to phenylephrine (PE), expressed as Emax (%). Protein expression of Intercellular Adhesion Molecule 1 (ICAM-1) was determined in myocardial tissue (% in relation to WKY). Results were expressed as mean ± SEM and effects of groups vs time were compared with mixed ANOVA.

Results
The results are shown in the table. We observed higher levels of SBP and DBP in SHR and Ob-SHR when compared to WKY, but with similar values between SHR and Ob-SHR groups. Regarding the structural LV changes, we observed LV remodeling and LA dilation in both SHR and Ob-SHR groups, but with no difference between both hypertensive groups. The Ob-SHR was the only group showing increased LVEDP in comparison to other groups. The Tau was also increased in the Ob-SHR animals. Concordantly, the Ob-SHR group showed increased expression of ICAM-1 (figure - A) that was concomitant to abnormal vascular response with increased contraction to PE (figure - B) as compared to SHR and WK groups.

Conclusions
In this translational model of HFpEF in rats, the structural changes related to LV remodeling were similar in SHR and Ob-SHR, probably reflecting comparable higher levels of blood pressure observed in both groups. In contrast, elevated EDP, a hallmark of HFpEF, was only seen in the Ob-SHR group and this was concomitant to diastolic dysfunction, endothelial inflammatory activation and altered vascular function. Our results indicate that obesity is a key factor inducing vascular and myocardial changes that triggers HFpEF phenotype in this model.
Association of epicardial adipose tissue with cardiac geometry alternation and diastolic dysfunction in the early stage of diabetic cardiomyopathy
Authors: Hsu J , Huang K C , Lin T T , Lee J K , Juang J M , Wu C K , Lin L Y 
Published: October 2024

Abstract

Background
Diastolic dysfunction and alterations in cardiac geometry are early indicators of diabetic cardiomyopathy. However, the association between cardiac changes across the glucose continuum and the contribution of epicardial adipose tissue (EAT) to these changes has not yet been investigated.

Purpose
In this study, we aim to investigated the EAT on cardiac diastolic function and structural alterations along the diabetic continuum using cardiac magnetic resonance imaging (CMR).

Methods
We enrolled individuals who were categorized into groups based on glucose tolerance status. Left ventricular structure and diastolic function were assessed using echocardiography and CMR to determine the EAT, intramyocardial fat, and associated parameters. Multivariate logistic regression models were also used.

Results
In a study of 370 patients (209 normal glucose tolerance, 82 prediabetes, 79 diabetes), those with prediabetes and diabetes showed increased heart dimensions and diastolic dysfunction, including E/E' (7.9±0.51 vs. 8.5±0.64 vs. 10.0±0.93, p=0.010), left atrial volume index (28.21±14.7 vs. 33.2±12.8 vs. 37.4±8.2 mL/m2, p&lt;0.001), and left ventricular peak filling rate (4.46±1.75 vs. 3.61±1.55 vs. 3.20±1.30 mL/s, p&lt;0.001). EAT significantly increased in prediabetes and diabetes (26.3±1.16 vs. 31.3±1.83 vs. 33.9±1.9 gm, p=0.001), while intramyocardial fat did not differ significantly. Prediabetes altered heart geometry, but not diastolic function (OR 1.22 [1.02–1.83], p=0.012; and 1.70 [0.79–3.68], p=0.135). Diabetes significantly affected both heart structure and diastolic function (OR 1.42 [1.11–1.97], p=0.032; and 2.56 [1.03–5.40], p=0.034) after adjusting for covariates.

Conclusions
Elevated EAT was observed in patients with prediabetes and is associated with adverse alterations in cardiac structure and diastolic function, potentially serving as an underlying mechanism for the early onset of diabetic cardiomyopathy.
Association of left ventricular ejection fraction improvement with prognosis in patients with cardiac sarcoidosis: insights from the ILLUMINATE-CS study
Authors: Maeda D , Matsue Y , Dotare T , Sunayama T , Yoshioka K , Nabeta T , Naruse Y , Kitai T , Taniguchi T , Tanaka H , Okumura T , Baba Y , Minamino T 
Published: October 2024

Abstract

Introduction
While the beneficial impact of enhancing left ventricular ejection fraction (LVEF) is well-documented in patients with heart failure with reduced LVEF, its relevance in cardiac sarcoidosis (CS) remains unclear.

Purpose
This study aimed to identify predictive factors for LVEF improvement and explore its association with prognosis in patients with CS.

Methods
A post-hoc analysis of the ILLUMINATE-CS registry, a retrospective observational study across multiple centers, was conducted. CS diagnosis adhered to either the 2016 Japanese Circulation Society guidelines or the 2014 Heart Rhythm Society expert consensus statement. Patients with baseline LVEF ≥50% were excluded in the current analysis. LVEF improvement was quantified as the variance between baseline and follow-up echocardiography. Patients were categorized into tertiles based on LVEF improvement: 1st tertile (≤0%, least improved), 2nd tertile (0–9%), and 3rd tertile (&gt;9%, most improved) groups. The primary outcome was all-cause mortality after follow-up echocardiography.

Results
Among 188 enrolled patients (mean age 62.1±10.7 years; 42.6% male), 65, 60, and 63 were allocated to the 1st, 2nd, and 3rd tertile groups, respectively. Multivariate linear regression analysis revealed that narrower QRS duration, lower baseline LVEF, and absence of beta-blocker prescription at baseline were independently associated with greater LVEF improvement. Over a median follow-up of 407 days, 26 all-cause deaths occurred. Kaplan–Meier curves exhibited significant difference among the tertile groups (log-rank, P=0.002). Cox proportional hazard analysis, adjusted for possible prognostic factors including LVEF, demonstrated significantly higher mortality in the 1st and 2nd tertile groups compared to the 3rd tertile group (vs. 1st tertile: hazard ratio [HR] 22.14, 95% confidence interval [CI] 2.73–179.50, P=0.004; vs. 2nd tertile: HR 8.17, 95% CI 1.02–65.71, P=0.048). Additionally, treating LVEF improvement as a continuous variable revealed an independent association with increased mortality (LVEF improvement per 5%: HR 0.69, 95% CI 0.54–0.87, P=0.002).

Conclusions
Improvement LVEF in patients with CS is significantly associated with improved outcomes, highlighting its clinical importance in managing CS.Kaplan–Meier curves for all-cause death
Predicting progression from coronary artery disease to heart failure in community cohorts
Authors: Pilbrow A P , Tragante V , Cameron V A , Jones G T , Helgadottir A , Troughton R W , Richards A M , Doughty R N , Patel R S , Asselbergs F W , Gudbjartsson D , Sulem P , Holm H , Stefansson K , Poppe K K 
Published: October 2024

Abstract

Background
Approximately 10% of people develop heart failure (HF) within 5 years after an acute coronary event. Once ischaemic damage has occurred, the heart undergoes remodeling, which can lead to subclinical dysfunction and HF. However, remodeling varies considerably between patients and is difficult to predict.

Purpose
To assess whether adding genetic information to clinical factors improves the accuracy of predicting incident non-fatal/fatal HF within 5 years in people with coronary artery disease (CAD).

Methods
In the UK Biobank (UKB) [1], we developed a clinical risk model (predictors age, sex, ethnicity, body mass index, social deprivation, smoking, personal medical history, time since most recent CAD admission, lipids, HbA1C, creatinine, medications). Separately, we performed a genome-wide association meta-analysis of 13,360 (6,315 + 7,045) cases and 58,126 (37,245 + 20,881) non-cases from the UKB and deCODE [2] cohorts, relating common genetic variants to non-fatal/fatal HF or cardiomyopathy in people with CAD. For the current analysis of the UKB cohort, we derived a polygenic risk score using summary statistics from deCODE alone. We then compared risk estimates and assessed reclassification of 5-year risk using the clinical risk model with and without polygenic risk score, in UKB. Risk groups were &lt;5%, 5-9.9%, 10-14.9%, ≥15%.

Results
Among people with CAD in the 5 years prior to assessment in UKB (n=8,880, mean age 61y, 27% women) or deCODE (n=10,113, mean age 66y, 34% women), 377 (4%) and 915 (9%) developed non-fatal/fatal HF over 5 years follow-up, respectively. In the UKB cohort, median 5-year risk with the clinical model was 3.2% (IQR 2-5.4%, C-statistic 0.72, 95% CI 0.70–0.74, Table 1) and plots of predicted versus observed risk showed very good calibration across deciles. The polygenic risk score was predictive of non-fatal/fatal HF in the UKB (hazard ratio 1.03, 95% CI 1.00 to 1.05 per standard deviation) with significance decreasing after adjusting for the prognostic index of the clinical risk model (hazard ratio 1.02, 95% CI 0.99 to 1.05 per standard deviation). Median 5-year risk by the clinical+polygenic model was 3.0% (IQR 1.9-5.0%). Net reclassification with the addition of the polygenic score improved accuracy of risk prediction for 3.6% of non-cases but deteriorated accuracy of risk prediction for 6% of cases. Overall net reclassification was deterioration of -0.025.

Conclusion
Our data suggest that common genetic variants may be associated with progression from CAD to HF, but that adding genetic data did not improve the accuracy of predicting progression from CAD to HF beyond established clinical predictors in the UKB cohort. Confirmation of these findings in deCODE and other large cohorts is warranted.
20 year picture of a heart failure clinic: changes in the patients profiles' and 2-year mortality
Authors: Carrete A , Codina P , Ruiz-Cueto M , Santiago-Vacas E , Borrellas A , Camblor A , Domingo M , Gonzalez B , Rivas C , Diez C , Troya M I , Boldo M , Julian M T , Lupon J , Bayes-Genis A 
Published: October 2024

Abstract

Background
Heart failure (HF) is one of the most prevalent diseases. Improvements in cardiac disease management in the last two decades and in HF itself might have influenced the referral of patients with HF to a specialised HF clinic.

Purpose
To evaluate changes in the profile of patients referred to an outpatient HF clinic over the span of 20 years, and to analyse trends in 2-year mortality.

Methods
A retrospective analysis of a prospective registry of HF patients in a specialised ambulatory HF clinic was conducted, from January 1st 2002 to December 31st 2021. We divided the 20 years of the study into five periods of four years each, in order to compare the clinical characteristics of patients at admission. The variables analysed include age, sex, aetiology, HF type (preserved - HFpEF, reduced - HFrEF, mildly-reduced - HFmrEF), NYHA class, left ventricle ejection fraction (LVEF), NT-proBNP level, number of previous hospitalizations, and treatment at referral (first visit). Two-year mortality was also analysed.

Results
A total of 2973 patients were included (mean age 67.1± 12,9, 69.7% men). Age remained stable across the five periods, p=0.43), while the referral of women increased throughout the study period (27.7% in 2002-2005 vs 32.9% in 2018-2021, p-for-trend=0.037). Patients with HFpEF were also increasingly referred (12.3% first period vs. 27.6% last period, p-for-trend&lt;0.001) and LVEF tended to be higher (33.09% vs. 40,9%, p&lt;0.001). The main aetiology of the referred patients was ischaemic heart disease, although it progressively decreased in favour of other aetiologies (Table 1) (p&lt;0.001). NYHA class tended to improve (NYHA 3-4 40.3% vs. 21.3%, p-for-trend &lt;0.001) and NT-proBNP levels tended to decrease, predominantly in the last period (p-for-trend=0.025), as well as hospitalisation rates in the previous year (p-for-trend&lt;0.001). Treatment with ACEi/ARB was progressively less frequent (p&lt;0.001), at least partially due to replacement by ARNi (p&lt;0.001). Treatment with digoxin and loop diuretics also diminished (p&lt;0.001 and p=0.04 respectively), whereas treatment with betablockers, ARM, ivabradine and SGLT-2i increased during the study periods (all p&lt;0.001) (Table 2); Patients carrying ICD and CRT also increased (p=0.014 and p&lt;0.001 respectively). Adjusted 2-year mortality significantly decreased, mainly in the last period (p&lt;0.001) (Figure 1).

Conclusion
The profile of HF patients referred to a tertiary HF ambulatory Clinic changed along 20 years of study. HFrEF remained the most common, but is declining in favour of HFpEF. Ischaemic aetiology also remained the most frequent but, again, showed a decreasing trend. Two-year mortality has globally decreased, markedly in the last period.Figure 1
Increased cancer incidence in patients with pre-existing heart failure: results from a French Nationwide Cohort study
Authors: Hulot J , Mirabel M , Nevoret C , Domenge O , Empana J P 
Published: October 2024

Abstract

Background
It is unclear whether patients with a history of heart failure (HF) have an increased risk of developing cancer.

Purpose
To assess the incidence of cancer (all types) in patients with pre-existing HF compared with patients without known HF at a nationwide level. Secondary objectives include analysis by cancer site and impact on all-cause mortality.

Methods
We used the French National Administrative Health Data System (SNDS), a comprehensive database containing all health care information (outpatient and hospital) for 99% of the French population, to identify adult patients with a first diagnosis of HF (ICD-10 diagnosis code I50) between 2010 and 2019 and without a personal history of cancer before HF diagnosis. HF patients were matched for sex and age to HF-free and cancer-free individuals (3:1 ratio), randomly identified in the SNDS. Incident cancers were identified by corresponding ICD 10th codes.

Results
We found 330,867 adult patients with a first diagnosis of HF between 2010 and 2019, and 992,601 matched controls (54.7% women, mean age 77.7±13.5 years in both groups). There was an increased risk of a first cancer in HF patients as compared to controls: 28,151 (8.5%) in HF patients over a mean follow-up of 4.3±2.8 years vs. 77,325(7.8%) in controls over a mean follow-up of 4.9±2.8 years (unadjusted HR: 1.12 [1.11-1.13], P&lt;0.001). The higher risk of new cancer in HF patients remained after adjustment for major comorbidities (i.e., ischemic heart disease, diabetes, arterial hypertension, renal dysfunction, morbid obesity), age, sex, year of diagnosis, region of residence, tobacco use and alcohol consumption (adjusted HR=1.06, [1.04-1.07]; P&lt;0.0001). Overall, the estimated attributable risk of new cancer after HF was 16.53% (9.88-16.76%). This increased risk was observed for most solid malignancies (especially colorectal and lung cancer), and for multiple myeloma. We finally observed that the risk of all-cause mortality after cancer diagnosis was significantly higher in patients with pre-existing HF compared to controls (adjusted HR: 1.36 [1.33-1.39], P&lt;0.001).

Conclusions
People with a history of HF have a higher risk of developing cancer than the general population. These findings suggest that cancer screening strategies should be encouraged in patients with HF.
Long-term clinical outcomes informed by artificial intelligence-enabled single-lead ECG detection of reduced ejection fraction
Authors: Alrumayh A , Kelshiker M A , Sau A , Mansell J , Almonte M , Chhatwal K , Bachtiger P , Peters N S 
Published: October 2024

Abstract

Background
* Reduced left ventricular ejection fraction (LVEF) is linked to poor clinical outcomes (1, 2).
* Despite its increasing prevalence, reduced LVEF is often undetected due to resource-limited echocardiography and lack of suitable point-of-care diagnostic tools.
* Previous studies have shown that an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm can accurately identify patients with reduced LVEF, but may also offer novel insights on long-term prognosis (3, 4).

Purpose
We aimed to determine if an AI-ECG algorithm designed for detecting reduced LVEF can also independently predict 2-year major adverse cardiovascular events (MACE) and all-cause mortality.

Method
* A retrospective multicentre observational study investigating the ability of AI-ECG to predict long-term clinical outcomes (i.e. over two years' follow up).
* Analysis included a total of 1,007 consecutive unselected patients attending for routine echocardiography, with a single-lead ECG recording performed at the same time.
* An AI-ECG algorithm, designed to identify impaired LVEF, was applied to each single-lead ECG.
* Occurrence of MACE and all-cause mortality associated with AI-ECG results (Figure 1) was investigated using Cox regression; evaluating performance of AI-ECG results as a classifier (0 or 1) and as a probability score (0 to 1).
* The study was approved by the UK Health Research Authority (reference 21/LO/0051).

Results
* The mean age was 62.3 years. 52.4% of patients were male and 57.5% of patients were White.
* Appropriately, patients with a positive AI-ECG had a higher MACE rate compared to those with a negative AI-ECG (34.2% vs. 11.9%; adjusted hazard ratio (aHR) 2.02; 95% CI, 1.46 – 2.81; p &lt; 0.005), primarily driven by increased mortality (23% vs. 9.6%; p &lt; 0.0001; aHR 1.65; 95% CI, 1.12 – 2.43) and heart failure hospitalization (14.5% vs. 1%; p &lt; 0.0001) – Figure 2.
* AI-ECG probability score (per 10% increase) was significantly associated with MACE (aHR 1.17; 95% CI, 1.09 – 1.25; p &lt; 0.005) and all-cause mortality (aHR 1.11; 95% CI, 1.02 – 1.20; p = 0.01).
* Importantly, sub-analysis of AI-ECG for those who have a normal LVEF (i.e. ≥50%) continued to show association between positive AI-ECG and MACE (27.2% vs. 11.9%; p &lt; 0.0001; aHR 1.70, 95% CI 1.17 – 2.48) and all-cause mortality (20.4% vs. 9.6%; p &lt; 0.0001; aHR 1.53, 95% CI 1.00 – 2.36).

Conclusion
An AI-ECG algorithm designed to identify impaired LVEF can identify patients at risk of MACE and all-cause mortality from single-lead ECG screening – regardless of their LVEF.
Such results may enable further risk stratification for cardiovascular investigations through the simple addition of single-lead ECG recording.
Longitudinal changes in the prevalence of indicators for the precursor stage B of heart failure: results of the STAAB study
Authors: Morbach C , Gelbrich G , Schmidbauer L , Sahiti F , Chen M , Cejka V , Frantz S , Heuschmann P U , Stoerk S 
Published: October 2024

Abstract

Background
The ACC/AHA guidelines on heart failure (HF) use selected echocardiographic signs of structural heart disease (SHD) as well as NT-proBNP levels to define the precursor stage B of heart failure in asymptomatic individuals.

Purpose
To study the change in prevalence over time of echocardiographic signs of SHD or elevated NT-proBNP levels in clinically inapparent individuals of the general population.

Methods
The STAAB study investigates precursor stages of HF in the general population of a medium-sized city in Germany (source population 124,297 inhabitants as of 2011 census). Participants, stratified for sex and age (30-79 years), were recruited between 12/2013 and 10/2017 from the source population if they had no preceding HF diagnosis and were followed for 2-4 years. Echocardiographic signs of SHD were (for exact definitions see table): left ventricular (LV) hypertrophy, LV dilation, reduced LV ejection fraction. Subjects with history of myocardial infarction, significant LV valve disease or symptomatic HF (Framingham criteria) were excluded.

Results
Of 4,965 subjects included at baseline, 3,684 (74.2%; mean age 55.2 years, 52.7% women) with at least one paired measurement were analysed. The changes observed over time in the prevalence of echocardiographic signs of SHD and elevated NT-proBNP levels are displayed in the table. Prevalences of echocardiographic signs of SHD increased (significantly for LVEF and LV dilation, trend for LV hypertrophy). Addition of NT-proBNP increased the cross-sectional prevalences, but not the change in prevalence of potential HF precursor stages.

Conclusion
The net incidence of clinically inapparent echocardiographic signs of SHD increased over time at a rate consistent with the prevalence observed for clinically apparent HF in the general population. Of note, not all echocardiographic findings will eventually result in symptomatic HF, and the classification is influenced by measurement errors. However, our data support the concept of HF precursor stages.