bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathophysiological insights into machine-learning-based subphenotypes of acute heart failure with preserved ejection fraction: a biomarker analysis of PURSUIT-HFpEF registry
Authors: Sotomi Y , Tamaki S , Hikoso S , Nakatani D , Okada K , Dohi T , Seo M , Masamichi Y , Hayashi T , Nakagawa A , Nakagawa Y , Ohtani T , Yasumura Y , Yamada T , Sakata Y 
Published: November 2023

Abstract

Background
Our understanding of heart failure with preserved ejection fraction (HFpEF) has evolved from mere left ventricular diastolic dysfunction to a multiorgan disease.

Purpose
This study aimed to investigate the heterogeneous pathophysiology of the several phenotypes of HFpEF with multiple biomarker data.

Methods
This study is a post-hoc analysis of the PURSUIT-HFpEF study (N=1,231), an ongoing, prospective, multi-referral center, observational study of acute decompensated HFpEF [UMIN000021831]. In this registry, there is a pre-defined sub-cohort in which we perform multi-biomarker tests (N=212). We applied the machine-learning-based clustering model that we have previously established to the sub-cohort and classified them into 4 phenotypes: phenotype 1 labeled as "rhythm trouble" (n=69), phenotype 2 "ventricular-arterial uncoupling" (n=49), phenotype 3 "low output and systemic congestion" (n=41), and phenotype 4 "systemic failure" (n=53). Characteristics of biomarker tests in each phenotype were evaluated.

Results
The phenotype 2 characterized by hypertension and cardiac hypertrophy showed the highest value of N-terminal pro-brain natriuretic peptide (NT-proBNP), IL-16, high-sensitive C-reactive protein (CRP), tumor necrosis factor (TNF)-α, growth differentiation factor (GDF)-15, troponin T, and cystatin C, whereas the phenotype 1 presented the lowest value of these markers. The phenotype 3 showed the second highest value of GDF-15 and cystatin C. The phenotype 4 presented a low NT-proBNP value and a relatively high GDF-15.

Conclusions
The specific characteristics of biomarkers in each phenotype confirmed the validity of the machine learning model-based classification. The contribution of inflammation to the pathogenesis considerably differed in different HFpEF phenotypes. Systemic inflammation substantially contributes to the pathophysiology of the classical HFpEF phenotype with cardiac hypertrophy.
Treatment of cardiomyocytes isolated from left ventricular myocardium of dogs with chronic heart failure with ALDA-1, an activator of aldehyde dehydrogenase-2, improves mitochondrial function
Authors: Sabbah H , Singh-Gupta V , Gupta R C , Castle K , Zhang K , Xu J 
Published: November 2023

Abstract

Background
Reactive oxygen species (ROS) generated by dysfunctional mitochondria (MITO) of the failing heart plays an important role in lipid peroxidation of polyunsaturated fatty acids in cell and MITO membranes resulting in the production of aldehydes, such as 4-hydroxy-2-nonenal (4-HNE). MITO aldehyde dehydrogenase-2 (mALDH2) is a key enzyme for the detoxification of endogenous aldehyde substrates through NAD dependent oxidation. ALDH2 catalyzes toxic 4HNE to nontoxic 4HNA in cardiac cells. We previously showed that mALDH2 expression and activity are markedly reduced in MITO of failing LV cardiomyocytes (CM), a maladaptation that can lead to considerable accumulation of 4-HNE in MITO and ultimately to progressive LV systolic and diastolic dysfunction. In this study, we tested the hypothesis that exposure of failing cardiomyocytes to ALDA-1, an activator of mALDH2, improves MITO function.

Methods
Freshly isolated CM from LV myocardium of dogs (n = 7) with heart failure (HF, LV ejection fraction ≤35%) and of normal (NL) dogs (n = 4) were incubated for 1 hour in absence (baseline) and presence of Alda-1 at concentration of 10 µM. After incubation, ADP-stimulated respiration (ADPresp) and maximal rate of ATP synthesis (ATPmax) were measured using Strathklein respirometer and bioluminescence ATP assay kit.

Results
Treatment of isolated CM from HF dogs with 10 µM Alda-1 significantly increased ADPresp (277 ± 18 vs. 189 ± 12 nAtom O/min/mg, p&lt;0.05) and ATPmax (30 ± 3 vs. 16 ± 3 nmoles/min/mg, p&lt;0.05) compared to untreated CM of HF dogs. Treatment of CM from NL dogs with 10 µM Alda-1 had no effect on ADPresp (488 ± 18 vs. 484 ± 19 nAtom O/min/mg) or ATPmax (54 ± 3 vs. 52 ± 2 nmoles/min/mg) compared to untreated NL CM.

Conclusions
Treatment of CM from HF dogs with Alda-1 improved overall MITO function. Activation of mALDH2 represents a potential viable therapeutic target for treating HF.
Effect of vitamin D receptor genetic polymorphism on the clinical response to angiotensin converting enzyme inhibitors therapy among breast cancer patients with chemotherapy induced cardiomyopathy
Authors: Al-Ansary I , Mokhtar R , Khorshid H , Schaalan M , Sarhan N 
Published: November 2023

Abstract

Background
Blockade of the renin-angiotensin-aldosterone system (RAAS) is the cornerstone treatment of chemotherapy induced cardiomyopathy (CIC) yet, variability in response to angiotensin converting enzyme inhibitors (ACEIs) acting on the RAAS is well-documented. Vitamin D was found to play a role in regulating RAAS. Previous studies revealed an inverse relationship between levels of vitamin D in serum and RAAS activation.

Purpose
The current study is primarily to evaluate the association between genetic variants in the vitamin D receptor (VDR) and clinical response to ACEIs among breast cancer patients receiving chemotherapy with CIC.

Methods
A total of 60 breast cancer patients with CIC (mean ejection fraction 30%) on β-blocker therapy were started on a ACEIs and followed for 6 months. Post-ACEIs-treatment changes in ejection fraction (EF) and serum potassium (K) were evaluated. We genotyped VDR gene polymorphisms including; ApaI (rs7975232), TaqI (rs731236), BsmI (rs1544410) and FokI (rs2228570) variants using TaqMan technique. Stepwise linear regression was performed to identify genetic and clinical factors associated with variability in ACEIs response, with adjustment for all potential confounding covariates.

Results
BsmI (rs1544410) (CT) heterozygous and TaqI (rs731236) (GA) genotypes had a significant increase in EF (12.8% and 10.8 %, respectively) and serum K (1.1 mEq/L and 0.91 mEq/L respectively); adjusted-p = 0.0001 and 0.004 for ∆EF and adjusted-p = 0.005 and 0.002 for ∆K. In contrast, (AA) homozygous carriers of the ApaI SNP (rs7975232) had a smaller increase in EF (∆EF = 1.2%) and K (∆K = 0.1 mEq/L) compared to (CA) (∆EF = 6.5%, ∆K = 0.73mEq/L) and (CC) (∆EF = 9%, ∆K = 0.9mEq/L) carriers; adjusted-p = 0.003 for ∆EF, adjusted-p = 0.004 for ∆K. Finally, for the FokI SNP (rs2228570), there was no significant change in EF and serum K level.

Conclusion
The results from this study highlight that BsmI (rs1544410) and TaqI (rs731236) are strong predictors of response to ACEIs therapy in chemotherapy-induced cardiomyopathy (CIC).
Prognostic value of 6-minute walking test for early prediction of doxorubicin induced cardiotoxicity
Authors: Muckiene G , Vaitiekus D , Zaliaduonyte D , Zabiela V , Verseckaite-Costa R , Juozaityte E , Jurkevicius J 
Published: November 2023

Abstract

BACKGROUND/OBJECTIVES
The 6-minute walking test (6MWT) is an easily performed, widely available and well-tolerated test for assessing the functional capacity of patients with HF in everyday clinical practice. The measurement properties of the 6MWT, such as reliability and validity, have been studied in patients with chronic heart failure, coronary artery disease, and cancer. However, little is currently known about the 6MWT and cardiotoxicity. The study was aimed at assessing the incidence of cancer therapy-related cardiovascular toxicity, identified the role of 6MWT as early predictor of early onset cardiotoxicity.

Methods
We performed a prospective study of 85 patients with breast cancer, treated with doxorubicin-based chemotherapy in the Department of Oncology and Hematology. 2D echocardiography and speckle tracking echocardiography were performed before anticancer treatment was started and after the treatment. We defined anthracycline-induced subclinical cardiotoxicity if a decline in global longitudinal strain (GLS) by &gt;15% from baseline was observed and based on that patients were divided into two groups– patients with subclinical cardiotoxicity and patients without subclinical cardiotoxicity. The 6MWT was developed by the American Thoracic Society comprehensive guidelines. The 6MWT was performed in a long straight hospital corridor, over a 30-m distance. Statistical analysis was performed with „IBM SPSS statistics 27.0" program. Statistical significance level p&lt;0.05.

Results
In the study population statistically significant GLS reduction was detected before and after the anticancer treatment (-21±0.53 vs. -18.1± 1.18, p&lt;0.01). Of 85 women (mean age, 54.5 (9.3) years) subclinical left ventricle dysfunction was identified in 51 (60%). We found a significant negative correlation between baseline 6MWT and cardiotoxicity (r = 0.3 and p = 0.02). The baseline 6MWT results were significantly lower among patients with subclinical cardiotoxicity (494.3 ± 40.5 m vs 629.8 ± 60.1 m, p&lt;0.001). The diagnostic validity of 6 MWT as a cardiotoxicity biomarker was evaluated using the non-parametric ROC curve (Pic. 1). We obtained an optimal cut-off point of 6MWT of ≤540m. (AUC = 0.98; p &lt; 0.001).

Conclusions
Baseline 6MWT may be used as independed prognostic predictor of subclinical anthracycline-induced cardiotoxicity.ROC curve for 6MWT and cardiotoxicity
Behavior of coronary sinus oxygen saturation and cardiac output in systolic heart failure
Authors: Mettke F , Kirsch K , Surber R , Schulze P C , Grosse A 
Published: November 2023

Abstract

Background
CRT implantation is indicated in advanced systolic heart failure (LV-EF &lt; 35%) on optimal medical therapy and left bundle branch block with wide QRS complex (QRS &gt; 150 ms). This study investigates the influence of different variables on venous saturation in the coronary sinus during HFrEF.

Methods
In this study, blood gas analyses (BGA) of patients undergoing CRT implantation were performed at our center. Patients with an electrophysiological study but without structural heart disease served as a control group.
In all patients a BGA from the coronary sinus was performed. Arterial and central venous saturation were used to determine cardiac output (CO) according to Fick's principle. Oxygen uptake was calculated from body surface area and age.

Results
In total, the study population included 19 patients in the CRT and 18 patients in the control group. The median age of the CRT group was 75 years (54-87 years) and in the control group 58 years (36-81 years). In the CRT group 53% had ischaemic cardiomyopathy.
The saturation in the coronary sinus was 30.3% in CRT patients and was therefore significantly lower than in the control group (40.0%, p = 0.02). However, CO at rest did not differ in both groups (CRT 6.8 L/min vs. control 7.4 L/min.). It was observed that the coronary sinus saturation was independent of CO and the genesis of heart failure. In contrast, QRS width before CRT implantation was negatively correlated with saturation in the coronary sinus (r = - 0.58, p = 0.01).

Conclusion
In patients with systolic heart failure and despite a normal CO, a decreased oxygen saturation in the coronary sinus at rest was found compared to cardiac healthy subjects. CS saturation correlates negatively with the width of the QRS complex. It is not dependent on age, LV function and the genesis of heart failure.
Associations between baseline heart rate and blood pressure and time to events in HFrEF patients: data from the QUALIFY international registry
Authors: Abdin A , Schoepe J , Anker S , Cowie M , Filippatos F , Wagenpfeil S , Ponikowski P , Tavazzi L , Komajda M , Boehm M 
Published: November 2023

Abstract

Aims
Low systolic blood pressure (SBP) and high resting heart rate (RHR) are both risk indicators for heart failure (HF) outcomes. The purpose of this analysis is to evaluate the associations between RHR and SBP at baseline and time to events in HF patients with reduced ejection fraction (HFrEF) in the QUALIFY international registry.

Methods and results
The QUALIFY registry enrolled 7317 patients with left ventricular ejection fraction (LVEF) ≤40% and previous HF hospitalization within 1–15 months. Complete Follow-up data were available from 5138 patients. The relationship between RHR and SPB on outcomes were analyzed according to baseline values as high RHR (H-RHR) ≥ 75 vs. low RHR (L-RHR) &lt; 75 bpm) and high SBP (H-SBP): ≥ 110 vs. low SBP (L-SBP): &lt;110 mmHg and analyzed according to each of the following 4 phenotypes: (H-RHR/L-SBP, L-RHR/L-SBP, H-RHR/H-SBP and L-RHR/H-SBP (reference group)). Compared to patients with reference group, patients with L-RHR/L-SBP had the highest all-cause mortality (hazard ratio (HR) 2,57, 95% CI 1.85–3.56 vs. HR 0.80, 95% CI 0.72–0.89, P&lt;0.001). After adjustment for age, Sex, NYHA, AF and eGFR rate, all-cause mortality remains the highest between the all groups (HR 2.62, 95% CI 1.88–3.66 P = &lt;0.001), followed by L-RHR/L-SBP (HR 1.74, 95% CI 1.24–2.45 P = 0.001 and H-RHR/H-SBP (HR 1.44, 95% CI 1.08–1.92 P = 0.01).
H-RHR/L-SBP and after adjustment was associated with the worst outcomes for other endpoints: CV death and HF hospitalization HR 1.83, CI 1.66-2.42, p = &lt;0.001), CV mortality (HR 2.7, CI 1.69-4.33, p = &lt;0.001) and HF hospitalization (HR 1.71, CI 1.30-2.25, p = &lt;0.001)

Conclusion
HFrEF patients, who have previously been hospitalized for HF presented with L-SBP and H-RHR, were at greater risk for all case mortality and CV death and HF hospitalization
Sex difference in incidence, risk factors of heart failure and subsequent mortality in general population: Results from the China PEACE million persons project
Authors: Qiu W , Cai A , Feng Y 
Published: November 2023

Abstract

Background
Epidemiological study of sex differences in incidence and risk factors of heart failure (HF), and subsequent mortality attributed to HF in the Chinese general population is lacking.

Purpose
To assess the sex differences in the incidence and risk factors of HF, and evaluate the population attributable fractions (PAFs) for the subsequent mortality among the Chinese general population.

Methods
Data were from a sub-cohort of the Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project in Southern China. Between 2016 and 2020, 102,358 community residents aged 35 to 75 from 8 sites in Guangdong Province were screened, and 80 individuals with a history of HF were excluded. Participants were divided into two groups by sex and the study outcome was HF incidence. Fine and Gray models were conducted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) accounting for the competing risk of all-cause mortality. Propensity score matching analysis and subgroup analyses were used to verify the robustness of the results. Adjusted PAFs of HF for all-cause and cardiovascular mortality were evaluated by sex.

Results
Of the 102,278 participants, 60.5% were women, and the mean age was 54.3 years. Compared with men, women were younger and less likely to smoke and drink, and had lower socioeconomic status and lower comorbid burdens. After a median follow-up of 3.52 years (343758 person-years), 1588 cases of incident HF (4.62 (95% CI: 4.40-4.85) per 1000 person-year) were identified. Compared with men (6.37 (95% CI: 5.95-6.80) per 1000 person-year), women had a lower incidence rate of HF (3.49 (95% CI: 3.24-3.75) per 1000 person-year, P&lt;0.001). After adjusting for the covariates, women had 31% (95% CI: 0.61-0.79) lower risk for HF than men. The results were consistent in the propensity score matching cohort and across all subgroup analyses (all P sex-subgroups interaction &gt;0.05). Although female was associated with a lower risk of HF, women had a higher PAF (24.2, 95% CI: 16.0-31.6) for subsequent cardiovascular mortality than men (16.5, 9%% CI: 11.3-21.5). Several significant differences in modifiable risk factors for HF were also noted between sexes.

Conclusion
In the Chinese general population, women were associated with a lower risk of HF but they have a higher cardiovascular mortality fraction attributed to HF than men. Sex-specific prevention strategies and therapies for HF should be warranted in the future.Graphic AbstractHF incidence across subgroups by sexes
Temporal shift in heart failure diagnoses among hospitalized patients within a large US integrated health system
Authors: Gluckman T , Chiu S T , Rider D , Tseng P , Mudd J , Remick J , Canonico M , Bonaca M 
Published: November 2023

Abstract

Background
Heart failure (HF) is a major cause of morbidity and mortality. Its rising prevalence and attributable cost have also made it a key focus in value-based care.
Historically, most HF admissions among Medicare beneficiaries in the US have been disproportionately accounted for by a limited number of International Classification of Disease (ICD) diagnosis codes (I50.2, systolic heart failure; I50.3, diastolic heart failure; and I50.4, combined systolic and diastolic heart failure). In 2017, however, a significant shift in assigned codes was observed nationally, with hypertensive heart disease with heart failure (I11.0) and hypertensive heart disease with heart failure and chronic kidney disease (I13.0 and I13.2) accounting for a large majority of assigned ICD-10 codes (1).

Purpose
To better understand the pattern of assigned ICD-10 codes among patients hospitalized for HF since 2017.

Methods
We performed a retrospective cross-sectional analysis of patients admitted to a large integrated health system within the western US between 1/1/2018 and 10/1/2022 with a principal diagnosis of HF (defined by one of the above ICD-10 codes). More specifically, we sought to further understand the demographics, clinical characteristics, and treatment patterns of HF patients across all payers as part of a quality improvement initiative. Patient-level analyses were not performed; rather, all hospitalizations were considered independent events.

Results
Over the nearly 5-year period, 61,238 HF hospitalizations occurred, involving 43,234 patients, with 76% having more than 1 hospitalization. Hypertensive heart disease with HF and chronic kidney disease was the most common HF diagnosis, accounting for just over half of all admissions (Figure). Hypertensive heart disease with HF was the next most common HF diagnosis, accounting for just over one-third of admissions. Consistent with the previous observed shift in HF diagnoses among US Medicare beneficiaries in 2017, systolic HF, diastolic HF, and combined systolic and diastolic HF accounted for &lt;10% of HF admissions in 2022.

Conclusions
Hypertensive heart disease with HF and chronic kidney disease and hypertensive heart disease with HF now constitute the predominant HF diagnoses for hospitalized patients across payers. This has important implications for quality improvement initiatives and health services research that utilize real-world data, as precise characterization of distinct phenotypes of HF may now be less reliant on coding than before.HF diagnoses (2018-2022)
Clinical red flags associated with transthyretin amyloid cardiomyopathy in patients with left ventricular hypertrophy: results of the TTRACK study
Authors: Damy T , Garcia-Pavia P , Piriou N , Cappelli F , Barriales-Villa R , Munteanu C , Bahus C , Keohane D , Mallaina P , Elliott P 
Published: November 2023

Abstract

Background
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a life-threatening, systemic disorder that results in progressive physical disability, substantially reduced quality of life, and high morbidity and mortality rates. ATTR-CM is an underrecognized cause of increased left ventricular (LV) wall thickness in older adults, and delayed diagnosis can lead to worse clinical outcomes. To facilitate early identification of patients with LV hypertrophy (LVH) at risk for ATTR-CM, greater recognition of diagnostic ‘red flags’ is required.

Purpose
To determine the association between diagnostic red flags and ATTR-CM in patients with LVH.

Methods
TTRACK is a multicentre, non-interventional epidemiological study (ClinicalTrials.gov: NCT03842163). Eligible patients were ≥50 years of age and had unexplained LVH (LV maximum wall thickness ≥15 mm [echocardiogram]). After undergoing technetium-99m-DPD/-PYP/-HMDP-labelled bone scintigraphy, scans were categorized by the degree of tracer uptake in the heart; Perugini grades 0, 1, 2 and 3 represented absent, low, moderate and high uptake, respectively. Immunofixation electrophoresis was used to detect monoclonal protein abnormalities; grade 2 and 3 scans without evidence of monoclonal gammopathy were considered diagnostic for ATTR-CM. The frequency of predetermined clinical disease markers was compared in patients without monoclonal protein abnormalities and grade 0 or grade 2/3 scans.

Results
Of 766 eligible patients with scintigraphy data, 521 (68.0%) had grade 0 cardiac uptake; 37 (4.8%) had grade 1; and 208 (27.2%) had grade 2/3. Among patients with moderate/high uptake, 137 (65.9% of those with grade 2/3 uptake; 17.9% of the overall cohort) had no monoclonal protein abnormalities (ATTR-CM); 56 (26.9%) had monoclonal gammopathy of undetermined significance or light chain amyloidosis; and 15 (7.2%) patients had unknown monoclonal test findings. On univariable analysis, carpal tunnel syndrome (odds ratio [95% CI], 27.7 [16.7, 46.1]), permanent atrial fibrillation (3.4 [2.2, 5.2]), male sex (2.9 [1.8, 4.8]) and advanced heart failure (1.8 [1.2, 2.9]) were the strongest predictors for grade 2/3 scans; on multivariable analysis, carpal tunnel syndrome (50.3 [23.4, 108.0]), male sex (9.1 [3.9, 21.3] and age (1.7 [1.4, 2.1]) were the strongest predictors (Figure).

Conclusions
In the TTRACK study, 18% of patients ≥50 years of age with unexplained LVH ≥15 mm had ATTR-CM. Carpal tunnel syndrome, male sex and advanced age were associated with a greater likelihood of ATTR-CM.