bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between heart rate, deformational echocardiographic parameters and clinical outcomes in patients with atrial fibrillation
Authors: Chao T , Liao J N , Hung C L , Lip G Y H
Published: October 2024

Background

The relationship between baseline heart rates and cardiac function in patients with atrial fibrillation (AF) remains unknown, as does its impact on long-term outcomes.

Methods

Patients with newly diagnosed AF and available echocardiography images were included. Conventional echocardiography measurement and myocardial deformation analyses using two-dimensional speckle-tracking echocardiography were performed during AF. Clinical endpoints included first-time hospitalization for ischemic stroke, heart failure (HF), all-cause mortality, and composite endpoint.

Results

Patients were categorized into groups according to baseline heart rates: 40-59, 60-69, 70-79, 80-89, 90-99, 100-109, 110-119, and ≥120 beats per minutes (bpm). As heart rates increased, there was a stepwise decrease of peak atrial longitudinal systolic strain (PALS: 14.6 ± 5.3%, 14.7 ± 5.5%, 14.1 ± 4.6%, 13.4 ± 4.7%,12.6 ± 4.9%, 12.1 ± 4.5%, 11.2 ± 5.2% and 10.8±4.1% in 40-59, 60-69, 70-79, 80-89, 90-99, 100-109, 110-119, and ≥120 bpm groups, respectively; P < 0.001)) and LV strain (-13.8 ± 3.9%, -14.5 ± 4.0%, -13.4 ± 3.4%, -13.4 ± 3.6%, -12.5 ± 3.6%, -11.9 ± 3.8%, -10.3 ± 3.8%, and -10.2 ± 3.8%, in 40-59, 60-69, 70-79, 80-89, 90-99, 100-109, 110-119, and ≥120 bpm groups, respectively; P < 0.001)(Figure). The lowest risk of composite endpoint was observed for patients whose heart rate between 60 to 69 bpm (Figure). Compared to the 60-69 heart rate group, faster heart rates were associated with increased risk of ischemic stroke (adjusted hazard ratios [aHR] 4.448 in the ≥120 bpm group), HF (aHR 1.909 in the ≥120 bpm group), mortality (aHRs 2.487, 2.810, 4.569, 4.760 in the 90-99, 100-109, 110-119, and ≥120 bpm groups, respectively), and composite endpoint (aHRs 2.034, 2.349, 3.492 in the 100-109, 110-119, and ≥120 bpm groups, respectively) (all P < 0.05).

Conclusion

In patients with AF, heart rate is closely linked to cardiac function and plays a pivotal role in long-term prognosis. Faster heart rates were associated with worse LA/LV functions and increased risk of clinical events. Favorable outcomes were found at heart rates below 100 bpm, with even better LA/LV function noted at heart rates below 80 bpm.
Prevalence of cardiovascular comorbidities among hospitalized patients with hypertrophic cardiomyopathy and factors associated with a higher case-fatality rate
Authors: Shoar S , Shoar N , Mujahid Z , Cascoperez A , Esparham A , Azargoon S , Asadi S
Published: October 2024

Background

Hypertrophic cardiomyopathy (HCM) is proven to be a catalyst for sudden cardiac death among affected population. However, the prevalence of cardiovascular comorbidities (CVC) and their association with in-hospital mortality has not been established among hospitalized patients with HCM.

Methods

National Inpatient Sample (NIS) database was queried from 2016 to 2020 to identify hospitalized patients with a diagnosis of HCM. The prevalence of CVC and case-fatality rate was determined for this patient population using univariate analysis and multivariate logistic regression.

Results

Weighted data was analyzed for a total of 278,995 admission cases with HCM. Crude in-hospital mortality rate increased from 16.4% to 22.9% during the study period. Atrial fibrillation (42.1%), HFpEF (28.1%), and cardiorenal syndrome (16.6%) were the most common CVC among hospitalized patients with HCM. The case-fatality rate was the highest among HCM patients hospitalized due to cardiac arrest (41%) followed by cardiac tamponade (13.7%) and STEMI (10.2%). Increasing age (aOR: 1.02, 95%CI: 1.02-1.03, p<0.0001), Asian/Pacific Islander race (aOR: 1.7, 95%CI: 1.1-2.4-, p=0.007), cerebrovascular accident (aOR: 2.3, 95%CI: 1.7-3.01, p<0.0001), NSTEMI (aOR: 1.8, 95%CI: 1.3-2.4, p<0.0001), peripheral vascular diseases (aOR: 1.3, 95%CI: 1.03-1.6, p=0.03), cardiorenal syndrome (aOR: 1.4, 95%CI: 1.2-1.8, p<0.0001), and cardiac arrest (aOR: 26.6, 95%CI: 20.9-33.9, p<0.0001). Among HCM patients with acute myocardial infarction requiring revascularization procedures, in-hospital mortality rate was significantly lower among those undergoing PCI than CABG (8.5% vs. 37.5%, p=0.008 for STEMI and 1.8% vs. 4.9%, p=0.04 for NSTEMI).

Conclusions

Mortality rate among hospitalized patients with HCM has been slightly on the rise over the last half century. Although aging population might be a contributing factor, comorbid end-organ damages including CVA, NSTEMI, and cardiorenal syndrome have demonstrated substantial association with in-hospital mortality in addition to cardiac arrest. For HCM patients requiring revascularization procedures, PCI seems to be associated with a lower mortality rate than its competitor CABG.
Survivability of young sudden cardiac arrest by aetiology: insights from a state-wide adjudicated cardiac arrest registry
Authors: Fahy L , Rowe S , Nehme Z , Stub D , Pflaumer A , Connell V , Semsarian C , Ingles J , La Gerche A , Paratz E
Published: October 2024

Background

Identifying factors to improve survival following out-of-hospital cardiac arrest (OHCA) is important. Many OHCA registries do not document the underlying cause of OHCA and therefore cannot provide insights according to specific arrest aetiology. The aim of this study was to assess survivability of OHCA according to arrest aetiology.

Methods

A state-wide registry identified all patients aged 1 to 50 years who experienced OHCA in Victoria, Australia from April 2019 to April 2023. OHCA was ambulance-defined with cause of OHCA determined by adjudication against autopsy or hospital data. OHCA aetiology was classified into four categories; non-cardiac, coronary, cardiomyopathy or other cardiac (including unascertained cause).

Results

2686 patients experienced OHCA (non-cardiac=1305, 48.6%, coronary=585, 21.8%, cardiomyopathy=250, 9.3%, other cardiac=537(282 unascertained), 20.0%), of whom 250 (9.3%) survived. Patients in the coronary group were older (median 45 years [interquartile range 40-48 years], p=0.0001), more likely to be male (83.6%, p<0.0001), have a witnessed arrest (44.6%, p<0.0001) and have an initial shockable rhythm (48.2%, p<0.0001) when compared to other categories. Using the non-cardiac group as the reference group, adjusted odds ratio of survival (95% CI) were 1.65 (0.86-3.19) for cardiomyopathy, 2.51 (1.55-4.07) for other cardiac and 4.03 (2.51-6.49) for coronary causes of OHCA.

Conclusion

Odds of survival to hospital discharge following OHCA were four times higher in OHCA of coronary aetiology when compared with non-cardiac OHCA. Ongoing research into OHCA according to aetiology is needed to define subgroups, benchmark resuscitation performance more appropriately and identify patterns according to specific aetiologies to improve survival outcomes.
Safety and efficacy of ultra-long intermediate-power ablation for outflow tract ventricular arrhythmia arising from the left ventricular summit
Authors: Futela P , Dai Q , Gupta A R , Ezzedine F M , Deshmukh A J , Garg L , Siontis K , Kowlgi G N
Published: October 2024

Background

Radiofrequency ablation (RFA) has been effective in managing premature ventricular contractions (PVCs). Despite improvement in ablation techniques, recurrence remains high for LV summit PVCs. Epicardial ablation here is often precluded due to fat and proximity to coronaries, thus, aggressive but safe endocardial options are needed.

Purpose

To evaluate the safety and effectiveness of ultra-long ablation (>240 seconds) duration for refractory LV summit PVCs.

Methods

Patients with deep intramural LV summit PVCs were identified by lack of PVC elimination or late (>60 s suppression) and recurrence post-lesion under the left aortic sinus of Valsalva. We included patients who received the longest RFA of at least 240 seconds (maximum 15 minutes). RFA power was titrated slowly from 20 to 35W, carefully ensuring that the impedance drop did not exceed 12 ohms. Acute procedure success was defined as clinical PVC suppression for ≥60 minutes after the last lesion. Short-term success was defined as symptom improvement, ejection fraction (EF) recovery, and drop in PVC burden at 3 months.

Results

Twenty patients (59.5 ± 16.4 years, 55% male) were included. Baseline features are shown in Table 1. All RFA were delivered endocardially. No steam pops were noted. PVC burden was significantly lower at 3-month follow-up (P< 0.01), Figure 1A. Most patients had a normal ejection fraction (EF) at baseline; thus, no significant difference change in EF was observed (Figure 1B). One complication was recorded, which was tamponade likely caused by coronary sinus dissection requiring pericardiocentesis. Acute success was achieved in 95.0% of the cases, and all cases followed at 3 months (18/18) achieved short-term success.

Conclusion

Ultra-long duration RFA with lesions ≥ 240 seconds at 35W per lesion for LV summit PVCs appeared to be safe and effective in achieving acute and short-term success. The lack of acute suppression should not discourage operators, as there seems to be delayed suppression in some cases. Careful monitoring of biophysics is paramount when attempting this technique.
Myocardial single photon emission computed tomography imaging to identify non-responders to cardiac resynchronization therapy in patients with non-left bundle branch block
Authors: Nakamura T , Ishibashi K , Ueda N , Oka S , Miyazaki Y , Wakamiya A , Nakajima K , Kamakura T , Wada M , Inoue Y , Miyamoto K , Nagase S , Aiba T , Kusano K
Published: October 2024

Background

Non-response to cardiac resynchronization therapy (CRT) is an important issue in the treatment of heart failure with reduced ejection fraction (HFrEF) and non-left bundle branch block (LBBB). Although the QRS duration and morphology are crucial parameters for selecting CRT candidates, electrocardiogram (ECG) markers may inadequately represent the mechanical activation patterns within the heart. Owing to limitations associated with the ECG criteria, there is increasing interest in advanced multimodality imaging to improve patient selection. Recently, myocardial single-photon emission computed tomography imaging (G-MPI) is used for assessing left ventricular (LV) dyssynchrony. This technique is mostly automatic and has high intra- and inter-observer reproducibility and repeatability.

Objectives

This study aimed to examine whether preoperative G-MPI evaluation could predict non-responsiveness to CRT in patients with HFrEF with non-LBBB.

Methods

Between January 2021 and December 2022, 128 patients underwent CRT, of whom 73 with pre-operative evaluation using G-MPI were selected. Forty-three patients with non-LBBB (21 and 22 CRT responders and non-responders, respectively) were assessed. These patients were divided into CRT responder and non-responder groups. We evaluated the cut-off and clinical impact of pre-operative G-MPI parameters in predicting non-responsiveness to CRT. In addition, 30 patients with LBBB were analyzed.

Results

Among patients with non-LBBB, CRT responders and non-responders showed no significant differences in baseline characteristics, except for the LV dimension. A receiver operating characteristic curve analysis identified 108° and 27.7° as the optimal cut-offs for the bandwidth and phase standard deviation (SD), respectively, to predict non-responsiveness to CRT (area under the curve [AUC]=0.762; 95% confidence interval [CI]: 0.601–0.923 and AUC=0.742; 95% CI: 0.576–0.909, respectively). A multivariate analysis revealed that a cut-off bandwidth of ≥108° and phase SD of ≥27.7° are independent predictors of non-responsiveness to CRT in patients with non-LBBB (hazard ratios 5.65; 95% CI: 1.53–20.9; P=0.009). In contrast, there were no relationships between G-MPI parameters and non-responsiveness to CRT in patients with LBBB.

Conclusions

Pre-operative G-MPI findings were associated with non-responsiveness to CRT in patients with non-LBBB. The identification of potentially nonresponsive patients could influence patient management and alter outcomes.
Significant correlation between the extent of myocardial fibrosis and heart failure parameters in patients undergoing transcatheter aortic valve implantation
Authors: Yamaguchi K , Matsushita K , Terasaka K , Hanajima Y , Tsustsumi K , Kirigaya H , Nakahashi H , Gohbara M , Kimura Y , Okada K , Ebina T , Cho T , Uchida K , Sugano A , Hibi K
Published: October 2024

Background

Recent studies have demonstrated that the prognosis of patients undergoing transcatheter aortic valve implantation (TAVI) is determined by the presence of myocardial fibrosis. The aim of this study was to quantify myocardial fibrosis in tissues obtained through myocardial biopsy before TAVI and to evaluate the relationship between the extent of myocardial fibrosis and baseline cardiac parameters.

Methods

We performed a retrospective single-center study, including 93 patients who underwent cardiac biopsies before TAVI from December 2022 to December 2023. The extent of myocardial fibrosis was assessed on Masson’s trichrome-stained tissue specimens, using a validated software "ImageJ".

Results

Median percent area of myocardial fibrosis in the entire cohort was 4.7% (interquartile range: 2.5 - 7.9). A significant correlation was found between the extent of myocardial fibrosis and brain natriuretic peptide (r= 0.41 p=0.0001), left ventricular ejection fraction (r=0.34, p=0.0009), aortic valve area index (r=0.33, p=0.0017), and global longitudinal strain (r=0.52, p<0.001). Patients who experienced prior heart failure hospitalization had a significantly larger extent of myocardial fibrosis (3.3% vs. 7.0%, p=0.0002).

Conclusions

Extensive myocardial fibrosis was associated with various heart failure parameters in patients undergoing TAVI. Patients with a large extent of myocardial fibrosis may require early intervention and/or intensive heart failure medical therapy to prevent fibrosis progression.
Deletion of mitochondrial DNA methyltransferase 1 contributes the development of murine heart failure under pressure overloaded
Authors: Omiya S , Otsu K
Published: October 2024

Background

Mitochondrial DNA (mitDNA) has similarities to bacterial DNA, which contains inflammatogenic unmethylated CpG motifs. We found that mitDNA that escapes from autophagy causes inflammatory response and heart failure under pressure overload. DNA methyltransferase 1 (DNMT1) maintains methylation patterns in somatic cells. Deletion of DNMT1 results in embryonic lethality in mice and mitotic catastrophe in cultured cells. Additional possible translational start sites (ATG1, ATG2) are located upstream of the commonly accepted nuclear DNMT1 translational start site (ATG3) and there is a conserved mitochondrial translocation signal sequence between ATG1 and ATG3. The role of mitochondrial DNMT1 in the development of heart failure remains to be elucidated.

Purpose

The purpose of this study is to examine the in vivo role of mitochondrial DNMT1 in the heart under pressure overload.

Methods

We generated HA-tagged DNMT1 constructs, 1) starting from ATG1 (termed as whole) 2) from ATG3 (nuclear) and 3) from ATG3 and mutated in the nuclear translocation sequence (mitochondrial) and transfected HEK293 cells with the constructs. Localization of HA-tagged proteins was assessed by immunocytochemistry. We also generated mitochondrial DNMT1-deficient mice by inserting mutations into the ATG1 and ATG2. The mice were subjected to pressure overload by means of transverse aortic constriction (TAC) to induce heart failure. Cardiac remodelling was assessed by echocardiography as well as histological analyses 4 weeks after operation.

Results

Whole, nuclear and mitochondrial DMNT1 translocated to both mitochondria and nuclei, only nucleus and only mitochondria, respectively. Mitochondrial DNMT1-deficient mice were born at Mendelian frequency and grew to adulthood. Those showed no cardiac phenotypes under baseline conditions. However, the mice exhibited severe systolic dysfunction, indicated by left ventricular fractional shortening, 2 weeks after surgery compared with control littermates (control littermates 47.9% versus Mitochondrial DNMT1-deficient mice 32.3%, p<0.05). Intermuscular cell infiltration was observed in TAC-operated mitochondrial DNMT1-deficient hearts.

Conclusions

Mitochondrial DNA methyltransferase 1 plays a protective role in failing hearts and mitDNA methylation might be a therapeutic target to treat patients with heart failure.
Proteomic profiling of extracellular vesicles in takotsubo syndrome
Authors: Zulfaj E , Nejat A , Pylova T , Krasnikova M , Elmahdy A , Espinosa A , Kakaei Y , Kalani M , Jha A , Haamid A , Redfors B , Omerovic E
Published: October 2024

Background/Purpose

Takotsubo syndrome (TS) is an acute form of heart failure characterized by transient regional wall motion abnormalities triggered by a stressful event. The mechanisms underlying its development and recovery are poorly understood, resulting in a lack of disease-specific treatments and diagnostic markers. Extracellular vesicles (EVs) play a significant role in cellular communication and have been shown to be important in various diseases. Their involvement in cardiac conditions like TS is an emerging area of research. The primary objective of this study is to isolate and characterize EVs, as well as profile their proteomic profile, from the heart tissue of rats induced with TS.

Methods

Rats underwent TS induction through the infusion of 1 mg/kg isoprenaline over 15 minutes (TS24h), or were given saline (control). High-resolution echocardiography verified apical ballooning at 6 hours. After 24 hours, heart tissues from apical and basal segments were collected and processed. EV isolation involved tissue slicing, enzymatic digestion, and differential centrifugation steps, including a final iodixanol cushion separation for large and small EVs (Figure 1). Tandem mass tags and mass spectrometry were utilized for global proteomics and any differentially expressed proteins (DEPs) were identified. Analytical techniques such as volcano plots, heatmaps, enrichment analysis, and protein clustering/networks were employed. The strongest clusters (lowest False Discovery Rate and highest intensity) were selected, and their Gene Ontology (GO) terms/pathways were identified.

Results

Pure, cup-shaped, vesicles ranging from 50-800nm were successfully isolated (figure 1). EVs from apex of control and TS24h hearts had lower protein concentrations compared to their corresponding basal segments. Global proteomic analysis revealed a distinct protein profile in EVs from the apical segment of TS hearts at 24 hours. A total of 256 (TS24h-apex vs control-apex) and 561 proteins (TS24h-apex vs TS24h-base) were differentially expressed. No DEPs were observed when comparing the basal segments of TS24h and control hearts. Functional enrichment analysis of the DEPs showed an abundant change of biological processes related to metabolic lipid processes, inflammatory response, complement activation, reorganization of extracellular matrix. A downregulation was seen for biological processes related to mitochondrial ATP synthesis coupled electron transport and muscle contraction.

Conclusion

This study demonstrates a distinct EV protein profile in the apical segments of TS hearts, with marked changes in proteins related to metabolic lipid processes, inflammation, and mitochondrial activity. This extensive catalogue of novel proteins sets the stage for future research aimed at identifying potential therapeutic targets and diagnostic biomarkers, and enabling proof-of-concept studies in TS.
Protease-activated receptor 2 (PAR2) inhibition reduces complement-associated cardiac remodelling in obesity-related heart failure
Authors: Ghanbari E , Meyer U , Doerner A , Kasner M , Barbieri F , Puccini M , Jakobs K , Witkowski M , Friebel J , Petzold T , Kraenkel N , Rauch B , Landmesser U , Rauch U
Published: October 2024

Background and Aims

Obesity is considered a major risk factor for the development of heart failure (HF) due to lipid accumulation, oxidative stress and inflammation which results in cardiac remodeling. Protease activated receptor 2 (PAR2) has been linked to various cardiovascular and inflammatory diseases. The role of PAR2 has not yet been studied in obesity-related HF.

Methods

In the experimental mouse study, we used 1-year-old ApoE knockout (ApoE-/-) and ApoE PAR2 double knockout (ApoE-/-PAR2-/-) mice with a C57BL/6J background on a high fat (HF) diet (n=5/ group). Cell culture experiments were performed with human primary cardiac fibroblasts and HepG2 hepatocytes. Patients (n=50) included in the clinical study had a BMI > 25kg/m², symptoms of heart failure (HF), coronary angiography (CA) that excluded coronary artery disease (CAD) and endomyocardial biopsy (EMB) that confirmed the absence of active myocarditis or primary cardiac amyloidosis. Patients were divided into PAR2low (n=22) and PAR2high (n=22) based on the median PAR2 expression measured via qPCR in the EMB of the cohort, and six patients served as healthy controls.

Results

Evaluation of endomyocardial biopsies (EMB) from overweight/ obese non-ischemic cardiomyopathy (NICM) patients with heart failure (HF) (n=44) revealed that a reduced cardiac PAR2 expression is associated with less cardiac C3 (p≤0.054), C4 (p≤0.041) and C5 gene expression (p≤0.045), as well as plasma levels of complement C3 (1.1g/l± 0.7 vs 2.1g/l±0.2; p≤0.016) and C5b-9 (303.4ng/ml± 215.7 vs 992.7ng/ml± 756.2; p≤0.0002) and as a result, better systolic function i.e. LVEF (46.1%±17.1 vs 36.8%±15.2; p≤0.046) and LV GLS (-14.9%± 5.7 vs -9.5%± 4.6; p≤0.009), less cardiac remodeling and damage. Correspondingly, aged ApoE-/-PAR2-/-mice on a Western diet showed less hepatic and cardiac complement expression (i.e. C1q, C3, C4, C5, C9), cardiac C3 deposition (p≤0.047) and C5b-9 plasma levels (p≤0.049), as well as less cardiac necrosis (p≤0.046) and lower BNP (p≤0.016) than ApoE-/-. PAR2 overexpression in human cardiac fibroblasts (HCFs) independently enhanced and PAR2 antagonism reduced interferon γ (IFNγ)-mediated STAT1-dependent complement C3, C4 and C5 expression.

Conclusions

Protease-activated receptor 2 regulates complement-mediated cardiac damage and remodeling in HF. The PAR2-IFNγ/STAT1/C3-C4-C5 complement-axis might be a promising prognostic and therapeutic approach to identify and treat high-risk cases of HF in overweight/obese patients.
Coronary microvascular dysfunction in patients with heart failure with reduced and mildly reduced ejection fraction: results from the PANACEA study
Authors: Nordberg Backelin C , Svedlund S , Bollano E , Hjalmarsson C , Pirazzi C , Brodin T , Dahllof K J , Lagerstrom Fermer M , Michaelsson E , Ohagen P , Wolfhagen Sand F , Lund L , Hage C , Ljungman C
Published: October 2024

Aims

Coronary microvascular dysfunction (CMD) is common and associated with impaired survival in patients with heart failure with preserved ejection fraction (HFpEF). In patients with heart failure with reduced ejection fraction (HFrEF) and mildly reduced ejection fraction (HFmrEF) the impact of CMD is not fully known.

Purpose

We aimed to investigate the prevalence of CMD and its association with phenotype, biomarkers, endothelial function and echocardiographic measurements in patients with HFrEF or HFmrEF.

Method

A prospective, exploratory bi-center study in patients with chronic stable heart failure, New York Heart Association (NYHA) Class II-IV, and ejection fraction (EF) <50% was performed. Study procedures included echocardiography, adenosine-based transthoracic Doppler echocardiography to assess coronary flow reserve (CFR), physical examination, fasting blood and urine sample, pulse wave velocity (PWV) and hemodynamic measurements. The cutoff of CFR<2.5 was used to diagnose CMD. A multivariable linear regression analysis with CFR as dependent variable, adjusted for age, sex, body mass index, smoking, atrial fibrillation and left ventricular mass, was performed to explore biomarkers, endothelial function, and echocardiographic measurements associated with CMD.

Results

Of 112 included patients, 87 (78%) were men, with a mean age of 73.3 (±7.5) years. Among patients with a successful CFR measurement (n=62), CMD was present in 40 (65%), mean age of 75.4 (±5.8) years (Table 1). Patients with CMD had higher N-terminal pro B-type natriuretic peptide (NTproBNP) and Troponin T (p<0.05), and more often HFrEF ( p=0.06). Patients with CMD had larger ventricles with greater left ventricular mass and larger end-diastolic volumes (p<0.05). In a linear regression analysis CMD was associated with higher NTproBNP, lower EF, PWV and global strain (table 2).

Conclusion

CMD was common and present in two thirds of patients with HFrEF or HFmrEF. Further CMD was associated with markers of more severe heart failure and systemic endothelial dysfunction indicating that CMD may be an important predictor of outcome in patients with HFrEF and HFmrEF.
Neurodegeneration is highly associated with comorbidity burden in HFrEF patients
Authors: Prausmueller S , Wurm R , Ponleitner M , Spinka G , Weidenhammer A , Arfsten H , Heitzinger G , Panagiotides N , Bartko P , Goliasch G , Stoegmann E , Hengstenberg C , Huelsmann M , Pavo N
Published: October 2024

Background

Heart failure (HF) is associated with cognitive decline and risk for dementia. Blood levels of amyloid beta 40 and 42 (Aβ40, Aβ42), tau protein (tau), and neurofilament light chain (NfL) have been found to be altered in neurodegenerative disease. Previous research has established a clear association between these neuromarkers and the risk of developing cognitive dysfunction and mortality in the general population.

Objective

The aim of this study was to investigate the association between the respective neuromarkers and comorbidity burden, as well as to explore whether comorbidity burden impacts the relationship between neuromarkers and outcome in HF patients.

Methods

Plasma levels of Aβ40, Aβ42, tau, and NfL were quantified using a single-molecule array assay. The primary outcome parameter was all-cause mortality.

Results

A total of 470 HFrEF patients were enrolled in the study, with a median age of 62 years (IQR: 52–72); 77% were male. Median NT-proBNP concentration was 1812 pg/ml (IQR: 718–3881). Elevated levels of all biomarkers were closely associated with comorbidity burden (Figure 1). All neuromarkers showed increased levels in individuals with chronic kidney disease (CKD) and known carotid artery stenosis (CAS), except for Aβ40, which did not show significant elevation in CAS (NfL: p<0.001 for both; t-tau: p<0.001 and p=0.041; Aβ40: p<0.001 and p=0.050; Aβ42: p<0.001 and p=0.033, respectively). In patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD), only NfL levels were significantly elevated (p<0.001 for both), whereas atrial fibrillation (AF) was associated with higher levels of NfL and t-tau (p<0.001 for both). In individuals with iron deficiency, only Aβ42 levels were significantly higher (p=0.025). All biomarkers showed significant associations with all-cause mortality [crude HR for an increase in 1-log unit (95%CI): NfL 4.44 (3.02-6.53), t-tau 5.04 (2.97-8.58), Aβ40 3.90 (2.27-6.72), Aβ42 5.14 (2.84-9.32); p<0.001 for all] (Figure 2). These associations remained statistically significant after adjusting for comorbidity burden including AF, T2DM, CAD, CKD, CAS and ID [adjusted HR for an increase in 1-log unit (95%CI): NfL 3.28 (1.93-5.57), t-tau 3.96 (2.07-7.57), Aβ40 2.42 (1.34-4.38), Aβ42 3.05 (1.56-5.97); p<0.01 for all].

Conclusion

The findings suggest a close connection between elevated levels of markers of neurodegeneration and increased comorbidity burden in HFrEF patients. While this association may indicate the cumulative risk leading to neuronal injury and HFrEF progression, a causal relationship cannot be excluded. The observed accelerated neurodegeneration in HFrEF underscores the need for further investigation into this complex interplay.Figure 1Figure 2
Twelve-lead electrocardiography-based artificial intelligence predicts the upcoming future of patients with heart failure with mildly reduced ejection fraction
Authors: Baek Y , Kim D Y , Lee S W , Lee S C , Choi W I , Kim D H
Published: October 2024

Background

Heart failure with mildly reduced ejection fraction (HFmrEF) has emerged as the predominant subtype of heart failure (HF), but there is a paucity of data for identifying it using artificial intelligence (AI) based electrocardiogram (ECG).

Purpose

This study aimed to develop artificial intelligence (AI)-ECG to identify and predict the prognosis of patients with HFmrEF.

Methods

We collected 104,336 12-lead electrocardiography (ECG) datasets from April 2009 to December 2021 in a tertiary center. The AI-ECG encompasses a novel model that combines an automatic labelling preprocessing method with a transformer architecture incorporating a triplet loss for HFmrEF analysis.

Results

The receiver operating characteristic analyses revealed that the area under the curve of AI-ECG for identifying all types of HF were acceptable (0.87, 95% confidence interval [CI]: 0.86-0.89), but that for identifying those with HFmrEF was relatively lower (0.83, 95% CI: 0.78-0.86) than those with HF with reduced ejection fraction (HFrEF) (0.89, 95% CI: 0.85-0.82) and those with normal ejection fraction (EF) (0.87, 95% CI: 0.85-0.89). The analysis of ECG features showed significant increases in QRS duration (p=0.001), QT interval (p=0.045), and corrected QT interval (p=0.041) with increasing ‘Severity by Euclidean distance’. Following the predictability analysis with another group of 1,134 patients for improvements of follow-up EF in HFmrEF, the patients were grouped into three clusters based on the AI- Euclidean distance; Cluster 1 had the most severe cases and poorer outcomes than Clusters 2 (p<0.001) and 3 (p<0.001).

Conclusion

AI-ECG presents an innovative approach for the prognostic stratification of cardiac contractility in patients with HFmrEF. By using AI-ECG, patients with HFmrEF will be able to predict upcoming disease progression.
Prognostic impact of myocarditis as aetiology compared with dilated cardiomyopathy and ischaemic heart disease in heart failure
Authors: Fu M , Pivodic A , Bollano E
Published: October 2024

Background

A subgroup of myocarditis can lead to heart failure. However, whether prognosis of myocarditis-induced heart failure differs from other heart failure remains largely unknown.

Aim

This study aimed to investigate the prognostic impact of myocarditis induced heart failure compared with heart failure with dilated cardiomyopathy and ischaemic heart disease as causes respectively in the overall population and a propensity score-matched cohort, based on patient-level data from the Swedish Heart Failure Registry (SwedeHF).

Methods

Patients with heart failure (HF) were enrolled from the SwedeHF (2003-2020) linked with the National Patient Register, and the Swedish Cause of Death Register. Endpoints were all-cause mortality, cardiovascular death, and hospital re-admissions, followed up from the index date until censoring or event.

Results

Of 54416 patients identified through the SwedeHF with HF, 418 hade myocarditis as aetiology (MC-HF), 6,871 with dilated cardiomyopathy (DCM-HF) and 47127 with ischemic heart diseases (IHD-HF). In general patients with MC-HF have shorter disease duration and less comorbidities compared with DCM-HF and IHD-HF, but older than DCM-HF and younger than IHD-HF. Compared with DCM-HF, MC-HF are associated with 29% higher risk for all cause mortality [(1.29 (1.07 - 1.55), p=0.0079] and 40% higher risk for cardiovascular death [ 1.40 (1.09 - 1.80), p=0.0088], and 19 % higher risk for heart failure rehospitalization [1.19 (1.03 - 1.37), p=0.018] and even higher risk by censoring within one-year . However, compared with IHD-HF, patients with MC-HF have similar risk for all cause mortality [0.95 (0.80 - 1.13), p=0.54], cardiovascular death [0.95 (0.75 - 1.20), p=0.65], and heart failure rehospitalization [0.93 (0.81 - 1.06), p=0.29]. Similar results were obtained from a propensity 1:2 matched cohort. No significant interactions were found regardless of age (< and < 70 years) , sex, LVEF (≥50%, 40-49%, 30-39% and < 30%) for all cause mortality comparing MC-HF vs DCM-HF, and MC-HF vs IHD-HF.

Conclusion

Patients with myocarditis-induced heart failure have worse outcome than heart failure due to dilated cardiomyopathy, with even higher risk during one year. This finding highlights the importance of early and more effective customized management of patients with myocarditis in particular those with high risk to develope heart failure.
Prognostic value of peak heart rate on cardiopulmonary exercise testing in patients with chronic heart failure
Authors: Shimono Y , Nakamura K , Nagai T , Ishizaka S , Omote K , Yasui Y , Aoyagi H , Tamaki Y , Mizuguchi Y , Takenaka S , Sato T , Kamiya K , Anzai T
Published: October 2024

Backgrounds

Many factors are known to be related to impaired exercise capacity or worse clinical outcomes in patients with chronic heart failure (CHF). Peak heart rate achievement by cardiopulmonary exercise testing (CPET) can be easily obtained on CPET. However, less data is available regarding the impact of peak heart rate on exercise capacity or long-term clinical outcomes in patients with CHF.

Purpose

We sought to investigate whether lower heart rate during peak exercise displayed poorer exercise capacity and worse clinical outcomes in patients with CHF.

Methods

We examined consecutive 435 patients with CHF referred for CPET in our university hospital between 2013 and 2018. The primary outcome was a composite of all-cause death or hospitalization due to worsening heart failure. Patients were divided into two groups according to the optimal cut-off value of peak heart rate based on receiver operating characteristic curve analysis.

Results

Patients with lower peak heart rate (≤112/min, n=164) were older and, higher brain natriuretic peptide level compared to those with higher peak heart rate (>112/min, n=271). Heart rate during peak exercise was significantly correlated with peak oxygen consumption (peak V̇O2) (Figure 1A), peak workload achievement (Figure 1B), and ventilatory efficiency (V̇E/V̇CO2 slope) (Figure 1C). There were 80 patients with events over a median follow-up period of 3.4 (Interquartile range 0.7–5.6) years. Patients with lower peak heart rate had about 3.0-fold higher risk of events compared to those with high peak heart rate (hazard ratio [HR] 3.17; 95% confidence interval [CI], 2.01–4.98) (Figure 2). In a multivariable Cox regression, 10 bpm-decreased in peak heart rate was associated with 12% increased adverse events (HR 0.88; 95%CI, 0.78–0.98).

Conclusions

Peak heart rate achievement on CPET was associated with reduced exercise capacity and worse clinical outcomes, suggesting that peak heart rate is useful for risk stratification in patients with CHF. Further study is required to identify therapies targeting peak heart rate to improve the exercise capacity or clinical outcomes in patients with CHF.Figure1Figure2
Defining patterns of comorbidity accrual before and after the diagnosis of heart failure
Authors: Macgowan H , Brown O , Walker A , Mcginlay M , Gierula J , Paton M , Straw S , Witte K , Drozd M , Kearney M , Cubbon R
Published: October 2024

Introduction

People with heart failure (HF) usually have multiple comorbidities and these confer adverse prognosis. The chronology of comorbidity development in relation to HF has not been investigated, which hinders development of preventative strategies.

Purpose

We aimed to define the chronology of comorbidity diagnoses in relation to HF diagnosis and hypothesised that HF is preceded by most of its comorbidities.

Methods

We used UK Biobank data to identify 21,127 people with HF diagnosis at any stage before or after recruitment. Comorbidities were defined using primary care records, and were not included if self-reported or their date of diagnosis unknown. Comorbidities were selected based on methods of Conrad et al. (Lancet 2018; 391(10120): 572-580), and defined using CALIBER or UK Biobank criteria. We investigated the time between first diagnosis of HF and first diagnosis of 15 common comorbidities, including after stratification by sex and age at HF diagnosis. Analysis was conducted using RStudio.

Results

For all studied comorbidities, except dementia, at least half of diagnoses predated or developed synchronously with HF. For myocardial infarction, obesity, cancer, atrial fibrillation, hypertension, diabetes and depression, at least three quarters of diagnoses predated or developed synchronously with HF. The median time between comorbidity and HF diagnoses varied substantially between comorbidities, ranging from depression preceding HF by 10.7 years to dementia proceeding HF by 0.7 years. The interquartile range of time between comorbidity and HF diagnoses varied substantially, ranging from 2.4 years for myocardial infarction to 15.2 years for depression, indicating most cases of the former develop in a narrow window (usually prior to HF diagnosis). All comorbidities presented earlier in women, with this being most marked for cancer (median time between cancer and HF -2.6 years for men and -7.1 years for women). As the age of HF diagnosis increased, the time spent with all studied comorbidities also increased. Indeed, in HF diagnosed before the age of 60, a majority of comorbidity diagnoses (except for depression) occurred after HF.

Conclusion

HF most often develops late in the process of comorbidity accrual, although this pattern is reversed in people developing HF at younger ages. Sex differences are also notable, with women developing comorbidities earlier in relation to their HF diagnosis. Understanding the chronology of comorbidity development may help to guide strategies to prevent multimorbidity, which are likely to require a personalised approach. For people with established HF, our data also emphasise the importance of holistic care that accounts for complex multimorbidity.Figure 1
Undetected heart failure in tertiary care: prevalence, predictors and outcomes
Authors: Rumora K , Puelacher C , Pargger M , Wussler D , Schaefer I , Lopez Ayala P , Durandi V , Walter J E , Hure G , Strebel I , Glarner N , Zellweger M J , Gualandro D , Pfister O , Mueller C
Published: October 2024

Background

Undetected heart failure (HF) seems to be unexpectedly common in primary care. We hypothesized that undetected HF may also be common in tertiary care, even in care pathways including cardiologists.

Methods

We assessed prevalence, predictors, and outcome of undetected HF in a large prospective cohort study enrolling patients referred for myocardial perfusion single photon emission tomography (MPI-SPECT) with central adjudication of HF according to guidelines. Findings were validated in two independent prospective cohorts (outpatient cardiac rehabilitation program, major noncardiac surgery). Prevalence of undetected HF, ratio of undetected HF to known HF and number needed to screen (NNS) were the primary endpoints.

Results

Among 3623 patients, median age 68 years, 31% women. 100 patients (3%) had known HF and 928 patients (25.6%) were adjudicated to have undetected HF, resulting in a ratio of undetected to known HF of 9.3-to-1 and a NNS of 2.8. Older age, atrial fibrillation, and previous pacemaker implantation were strong independent predictors of undetected HF. Patients with undetected HF were at significantly higher risk of cardiovascular death or HF hospitalization (adjusted HR 1.47 [95%CI, 1.17-1.85] versus no HF). These findings were confirmed in both validation cohorts: among 970 and 1563 patients the prevalence of undetected HF was 21.5% and 19%, ratio of undetected HF to known HF 0.7-to-1 and 2.8-to-1, NNS 2.2 and 3.7, respectively.

Conclusion

The prevalence of undetected HF is high also in tertiary care, even higher with older age, atrial fibrillation, and previous pacemaker implantation, and associated with increased risk of cardiovascular death or HF hospitalization.Prevalence of undetected HFKaplan-Meier cumulative incidence curves
The association between endogenous erythropoietin levels and the risk of heart failure in a Chinese community-based population
Authors: Xie H , Gong Y J , Fan F F , Jia J , Zhang Y
Published: October 2024

Background

Patients with heart failure (HF) often have elevated endogenous erythropoietin (EPO) levels, which are associated with disease severity and prognosis. Previous studies have indicated that in the special population elevated endogenous EPO levels are associated with HF and cardiovascular death. However, whether endogenous EPO levels are associated with the risk of HF in the general population remains to be elucidated.

Purpose

Our study aims to investigate the association between endogenous EPO levels and the risk of HF admission in the general population.

Methods

We conducted a prospective cohort study on subjects from a Beijing community in China who had no history of stroke or myocardial infarction. Endogenous EPO levels were measured at baseline for all participants. The endpoint of interest was admission with HF. Cox proportional hazard regression models were used to analyze the relationship between endogenous EPO levels and the occurrence of the endpoint.

Results

A total of 4870 participants were included. Among all participants, the mean (±SD) age was 56.72 ± 8.78 years, with 1802 (37.0%) being men. The median (interquartile range, IQR) EPO level was 13.19 (9.47-18.20) IU/L. During a mean 9.57-year follow-up, a total of 176 (3.6%) subjects experienced heart failure. Subjects were grouped in quintiles according to baseline endogenous EPO levels. Higher and lower endogenous EPO levels were both associated with increased risk of HF (Figure 1A). The Kaplan–Meier curves showed significant differences in cumulative hazards of heart failure among EPO quintiles (log-rank test: P＜0.05) (Figure 1B). After adjusting for covariates, including demographics, traditional risk factors for cardiovascular disease, renal function, and hemoglobin levels, and using the middle quintile (Q3) (11.72-14.94IU/L) of EPO levels as a reference, we found that the highest quintile (Q5) (>19.86 IU/L) was associated with a 159% increased risk of HF admission (HR 2.59, 95% CI 1.57-4.28, P = 0.0002). Similarly, the lowest quintile (Q1) (<8.66 IU/L) was associated with a 94% increased risk (HR 1.94, 95% CI 1.11-3.41, P = 0.0210) (Table 1).

Conclusion

There exists a "U-shaped" relationship between endogenous EPO levels and HF admission in the general population. Both higher and lower endogenous EPO levels were associated with an increased risk of HF admission in the community population. These findings differ from previous studies, so further research may be needed to explore the underlying pathophysiological mechanisms of endogenous EPO and HF.
Hyponatremia and risk of new-onset heart failure in patients with type 2 diabetes - a real-world study of 70,000 patients
Authors: Malik M E , Koeber L , Garred C H , Zahir D , Jensen J , Jensen M H , Holt A , Andersson C , Fosboel E , Mohamed A A , Binding C , Mcgettigan P , Schou M
Published: October 2024

Background

Hyponatremia is common in patients with heart failure and in patients with type 2 diabetes (T2D), and is a risk marker for increased morbidity and mortality. However, it is unclear whether hyponatremia in patients with T2D is associated with an increased risk of new-onset heart failure.

Purpose

To investigate whether hyponatremia is associated with an increased risk of new-onset heart failure in patients with T2D.

Methods

From Danish nationwide registers, all patients with T2D with no history of heart failure were identified from 2013-2021. Patients with at least two samples of plasma sodium measured (at least one month apart), during the first six months following their T2D diagnosis, were included with follow-up start six months after T2D diagnosis as well. Patients were categorized in two groups according to the mean plasma sodium concentration at baseline: 1) sodium >137 mmol/L; and 2) sodium <137mmol/L. Cumulative incidence curves and Cox proportional hazards models (crude and adjusted for age, sex, comorbidities, and potential hyponatremia-inducing medications including diuretics, anticonvulsants, and antidepressants) were used to investigate the association of sodium concentration with the incidence of heart failure during follow-up. Incidence rates of heart failure per 1000 person-years were calculated across the spectrum of the measured sodium levels.

Results

We included 69,750 patients where 57% were male and the median age was 63 (interquartile range: 54-71). At index, 57,723 (83%) patients had a mean sodium concentration of >137 mmol/L and 12,027 (17%) patients had a mean sodium concentration <137 mmol/L (hyponatremia). Patients with a sodium level <137 mmol/L were associated with a significantly higher hazard rate of heart failure compared to patients with sodium concentrations >137 mmol: adjusted hazard ratio (HR) 1.27 (95% confidence interval 1.15-1.41, p-value <0.001). In analyses where sodium concentration was considered a continuous variable, increasing concentration of 1 mmol/L was associated with a decreasing hazard rate of heart failure: adjusted HR 0.96 (0.94-0.97, p-value <0.001).

Conclusions

Hyponatremia was common and associated with a significantly higher risk of new-onset heart failure in patients newly diagnosed with T2D. Whether hyponatremia could be a new treatment target to prevent heart failure in T2D remains to be determined.Cumulative incidence of heart failureIncident heart failure