bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smaller intrinsic QRS area and smaller reduction of QRS area during cardiac resynchronisation therapy are associated with higher risk of ventricular arrhythmias and appropriate ICD therapy
Authors: Marinko S , Platonov P G , Borgquist R 
Published: October 2024

Abstract

Background
Cardiac resynchronisation therapy (CRT) patients are at high risk for ventricular arrhythmias (VAs), and little is known about which characteristics are associated with an increased risk for arrhythmic events.

Purpose
To investigate the association between QRS area parameters and the risk for VAs in patients with heart failure undergoing primary preventive CRT with defibrillator (CRT-D) implantation.

Methods
All patients receiving CRT-D between 2015 and 2020 at a large-volume tertiary care center were retrospectively evaluated. Digital 12-lead electrocardiograms (ECGs) were collected before and after CRT implantation. Patients were included if they had native LBBB and were implanted with a primary preventive CRT-D. Kors’ regression transformation was used to derive vectorcardiographic QRS area from the 12-lead ECGs. QRS area parameters were analysed in relation to a primary endpoint of first appropriate ICD therapy, i.e., ATP or shock therapy.

Results
177 patients with LBBB (68.9 years [60.7–73.8]; 21.5% female; 52.9% New York Heart Association (NYHA) class III-IV; LVEF 25.9±6.3%) were followed over a median follow-up time of 2.5 years [1.6–3.0] after CRT-D implantation. 27 patients reached the primary endpoint. The median pre-CRT QRS area was 134.5 μVs [102.3–163.8]. Multivariable Cox regression identified a small pre-CRT QRS area (HR, per 10 μVs decrease, 1.30; [1.12–1.51]; p=&lt;.001) and a small post-CRT reduction in QRS area (HR, per 10 μVs decrease, 1.30; [1.13–1.49]; p=&lt;.001) as independent predictors of an increased risk of appropriate ICD therapy. In analyses with a scoring variable combining pre-CRT QRS area and QRS area reduction both above or below median, the combination of a small pre-CRT QRS area and a small QRS area reduction was strongly associated with an increased risk of reaching the endpoint (HR, per point increase, 2.47; [1.2–4.9]; p=0.01).

Conclusion
A small intrinsic QRS area, by itself or in combination with a small reduction of post-CRT QRS area, was strongly associated with a higher risk of ventricular arrhythmias in this cohort of CRT-D treated patients. In conjunction with other parameters, further risk stratification for arrhythmic events could be achieved by assessing QRS area data pre- and post-CRT.Figure 1.K-M pre-CRT QRS area quartilesFigure 2.K-M QRS area score
Comparative safety outcomes of leadless versus transvenous cardiac pacemaker: a systematic review and meta-analysis
Authors: Ohn M H , Luen N P , Jouhra F , Ahmed F Z 
Published: October 2024

Abstract

Introduction
Leadless Cardiac Pacemakers (LCP) have emerged as a promising alternative to Transvenous Pacemakers (TVP) for managing bradyarrhythmias, especially in cases where TVP options are limited, such as venous access issues in haemodialysis patients or high infection risk individuals. However, long-term safety data, including mortality and hospitalisation rates, are lacking, hindering informed clinical adoption decisions.

Purpose
This systematic review and meta-analysis compares safety endpoints of LCP with TVP.

Methods
A systematic search of PubMed, Medline, Embase, Scopus, Web of Sciences, and gray literature was conducted following PRISMA guidelines from release of the Micra LCP to market until May 15, 2023. Meta-analysis was performed using RevMan 5.4.

Results
Twenty-four studies including data from 33,450 patients (12,802 LCP, 20,648 TVP) were evaluated. The mean age of the population was 77.5 ± 10.6 years, with a mean left ventricular ejection fraction (LVEF) of 58.6 % ± 6.7. Follow-up durations ranged from 6 to 36 months. Compared to TVP, the LCP was associated with significantly fewer overall complications, major complications, acute, mid-term complications, hospitalisations, re-interventions, and device dislodgements (p&lt;0.05). Mortality, tricuspid regurgitation, pacemaker-induced cardiomyopathy, and heart failure hospitalisation rates did not significantly differ. Although LCP showed higher cardiac injury risk, no significant difference in cardiac tamponade rates was observed (Figure 2). LCP exhibited increased vascular-related complications but decreased lung injury, endocarditis, device, and pocket-related issues.

Conclusion
In the largest review of LCPs, we report that LCP is associated with significantly lower rates of overall complications compared to conventional TVP. This knowledge is critically important as more LCPs enter clinical practice and serves as a baseline against which future data can be evaluated. Nevertheless, proper skill training may help to mitigate the risk of vascular and cardiac injury. These findings underscore the importance of conducting randomized controlled trials to comprehensively evaluate the safety of LCP compared to TVP.Cardiac complication
Safety and efficacy of leadless pacemaker extraction using a novel retrieval tool: a multicenter analysis
Authors: La Fazia V , Carola Gianni C G , Brandon Doty B D , Kirollos Gabrah K G , Domenico Giovanni Della Rocca D G D R , Nicola Pierucci N P , Mohanty Sanghamitra M S , Preem Geeta Torlapati P G T , Mohamed Bassiouny M B , Amin Al-Ahmad A A A , Luigi Di Biase L D B , Rodney Horton R H , Weeduran Bode W B , Devi Nair D N , Andrea Natale A N 
Published: October 2024

Abstract

Background
Leadless pacemakers (LP) have emerged as a safe and effective alternative for cardiac pacing, increasingly adopted by the medical community. While rare, complications such as pacemaker syndrome or device dislodgment can occur. In such instances, the extraction of the leadless pacemaker and its replacement with a new device should be considered.

Purpose
This multicenter study aimed to describe the use of the Aveir retrieval sheath during Micra extraction procedure and to assess the success rates and potential complications associated with the procedure.

Methods
In this observational study, we analyzed prospectively collected data from 14 patients that underwent leadless pacemaker using Abbott retrieval catheter at three high volume centers for pacemaker extraction and leadless implant in United States.
Thought femoral vein the Aveir steerable retrieval catheter is advanced to the right atrium and then across the tricuspid valve. Under TEE and fluoroscopy guidance the snare is advanced over the Micra, and the button is secured. A protective sleeve is advanced over the LP. With application of traction to snare and countertraction with the sleeve against the endocardium, the LP is free from the myocardium and removed via the sheath. (Fig. 1)
The procedural duration should be intended as the combined total of the time taken for the extraction of the existing pacemaker and the implantation time of the new device.
Extractions performed during the first year were described as early and thereafter as late.
Procedural success was described as complete extraction of LP without procedural complication.

Results
The reason for early explant was LP dislodgment and for late explant was pacemaker syndrome. Median time to extraction was 4±2 months in early explant and 35±9 months in late explant. Procedural time in early and late groups was 68.7 and 72.3 min respectively (P=0.32). Fluoroscopy time in early and late groups was 12.2 and 16.4 respectively (P= 0.18). LP was then replaced with a transvenous pacemaker. Success was 100% in both groups. No complication occurred in both groups.

Conclusion
Micra pacemaker using Aveir retrieval catheter is an effective tool irrespective of dwell time.
The prothrombotic state in patients with type 2 diabetes mellitus and ischemic heart failure: an association with endothelial dysfunction
Authors: Nowak K , Siniarski A , Karcinska A , Yika A D C , Matrejek A , Stepien K , Nessler J , Gajos G , Zalewski J 
Published: October 2024

Abstract

Background
Heart failure (HF) is associated with a substantial prothrombotic state and an increased risk of thromboembolism, regardless of the presence of atrial fibrillation (AF). Although oral anticoagulation in HF with known AF is recommended, there is no conclusive evidence supporting clinical benefits of chronic anticoagulation in HF subjects without AF. Other factors enhancing prothrombotic state, often concomitant with HF, are type 2 diabetes mellitus (T2D) and coronary artery disease (CAD). T2D as well as CAD are independently associated with a hypercoaguability due to multiple mechanisms including endothelial dysfunction and oxidative stress. Dysfunction of endothelium was observed in patients with HF, however a little is known about its influence on prothrombotic state in a very high risk HF population.

Purpose
This study aimed to investigate whether the prothrombotic state in patients with T2D, CAD, and HF, depends on the left ventricular ejection fraction (LVEF) or endothelial function.

Methods
We assessed 54 patients with stable chronic HF, CAD, and T2D. Based on the echocardiography examination 28 of them were those with HF with reduced ejection fraction (HFrEF) and 26 of them were classified as HF with preserved ejection fraction (HFpEF) according to current guidelines. Fibrin clot density reflected by clot permeability (Ks) and thrombin generation were evaluated. Endothelial function was determined in flow-mediated (FMD) and nitroglycerin-mediated dilatation (NMD) tests of the brachial artery.

Results
Subjects in both groups were comparable in terms of cardiovascular risk factors except for lower glomerular filtration rate (GFR) by 18.1%. HFrEF patients had lower Ks by 20.3%, along with higher endogenous thrombin potential (ETP) by 18.9% and maximum thrombin level (Peak) by 24.1% as compared with HFpEF. While there were no differences in FMD and NMD between subjects, we found negative correlations of NMD with ETP and Peak (r=-0.448, P=0.001; r=-0.304, P=0.034, respectively). Moreover, the proportion of NMD and FMD along with GFR and LVEF were also significantly associated with both thrombogram parameters (&lt;0.01 for all). By the multivariate analysis of the whole population, NMD, LVEF, low-density lipoprotein and GFR were independent predictors of ETP (R2=0.530, P&lt;0.001) while NMD, LVEF, and GFR predicted Peak levels (R2=0.327, P=0.002).

Conclusion
We showed for the first time that patients with ischemic etiology of HFrEF and T2D presented altered fibrin clot properties and enhanced thrombin generation compared to HFpEF subjects. It might be hypothesized that endothelial dysfunction induced by T2D could intensify hypercoagulability in patients with HF.Figurę 1
The impact of left venticular filling pressure indexed to cardiac output on exercise capacity in heart failure subjects
Authors: Huang W M , Sung S H 
Published: October 2024

Abstract

Background/Introduction
Exercise intolerance is the most common symptom of patients with heart failure (HF), regardless of the phenotypes. We aim to investigate the determinants of exercise capacity in chronic stable HF with reduced, mildly reduced, preserved, and recovered ejection fraction (EF).

Methods
Ambulatory HF subjects were recruited for a combined cardiopulmonary exercise test and exercise stress echocardiography. Peak oxygen consumption (peak VO2) and minute ventilation-carbon dioxide production relationship (VE/VCO2 slope) were obtained. Impaired exercise capacity was referred to a peak VO2 of &lt;14 ml/kg/min, and a VE/VCO2 slope of &gt;34 was defined as ventilatory inefficiency.

Results
Among a total of 66 participants, there were 16 HF with reduced EF, 18 HF with mildly reduced EF, 12 HF preserved EF, and 20 HF recovered EF. While both LVEF, global longitudinal strain (GLS), E/e’ ratio and diastolic dysfunction indices were crudely associated with peak VO2 and VE/VCO2 slope, only diastolic dysfunction indices were independently predictive of impaired exercise capacity (odds ratio and 95% confidence intervals: 3.847, 1.369-10.810). GLS at rest was independently correlated with ventilatory inefficiency (1.404, 1.050-1.877). Among the exercise indices, the peak medial E/e' to cardiac output ratio was independently associated with impaired exercise capacity (3.478, 1.313-9.214) and peak GLS was best related to ventilatory inefficiency (1.403, 1.076-1.828).

Conclusions
Among resting and exertional echocardiographic variables, the peak medial E/e' to cardiac output ratio, a non-invasive assessment of exertional left ventricular filling pressure indexed to cardiac output, was the major determinant of exercise capacity in patients with different HF phenotypes.
A novel risk score incorporating frailty or congestion status predicted mortality in patients with heart failure with preserved ejection fraction.
Authors: Iwakura K , Tanaka N , Okada M , Okamura A , Watanabe H , Seo M , Hayashi T , Yano M , Yamada T , Yasumura Y , Hikoso S , Okada K , Nakatani D , Sotomi Y , Sakata Y 
Published: October 2024

Abstract

Introduction
In patients with heart failure (HF), frailty or congestion is strongly associated with clinical outcomes. However, existing risk prediction models for HF prognosis do not incorporate these important clinical factors. The estimated plasma volume status (ePVS) is an easy-to-calculate index to estimate plasma volume. which is associated with the prognosis in HF patients.

Purpose
This study intends to construct an inclusive risk prediction model for all-cause mortality in patients with HF with preserved ejection fraction (HFpEF), incorporating evaluations of frailty and congestion alongside traditional risk factors.

Methods
We analyzed data from 1212 patients (81±9 years, 55% female) registered in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study, a multicenter registry of patients hospitalized for acute decompensated HFpEF. We evaluated clinical factors including Clinical Frailty Scale (CFS) and blood test results collected before discharge. We calculated ePVS at discharge using the Duarte formula as ePVS (mL/g)=100×(1-hematocrit)/hemoglobin (g/dL). Patients were followed for median of 713 days (IQR 369-1088 days) to observe all-cause death.
Patients were randomly assigned to the derivation and validation cohorts (2:1 ratio). Using the Bayesian Information Criterion (BIC), a stepwise model selection was executed on 51 clinical parameters, including CFS and ePVS, to identify independent predictors of mortality. A risk model for mortality was constructed based on these predictors and their coefficients. The accuracy of the risk score was validated using time-dependent ROC curves both in the derivation cohort (n=801) and in the validation cohort (n=411).

Results
During the follow-up period, all-cause death was observed in 315 patients (25.9%). Age, sex, CFS, NT-proBNP and ePVS were selected as independent predictors of all-cause death. The score shown in the Table was applied to each factor, and the sum of the scores was calculated as the risk score. The AUC of the risk score for predicting 1-year mortality in the derivation cohort was 0.79 (95% CI 0.74, 0.85). The optimal cut-off value of 6 provided a sensitivity and specificity of 74.9% and 74.4%, respectively. The AUC for 1-year mortality in the validation cohort was 0.70 (95% CI 0.63, 0.77).

Conclusions
The novel risk prediction model incorporating CFS and ePVS effectively predicted mortality in HFpEF. This model could be a valuable tool for risk stratification.Table
Effect and mechanism of Adipokine Omentin-1 on cardiac hypertrophy in heart failure with preserved ejection fraction
Authors: Li Q X , Liu Z Q , Ma X T , G F , Wang Z J 
Published: October 2024

Abstract

Background
Omentin-1 secreted by epicardial adipose tissue can inhibit ventricular remodeling and improve early cardiac function after myocardial infarction. Our previous studies have identified the omentin-1 receptor as integrin receptors αvβ3 and αvβ5. However, the effect of omentin-1 on heart failure with preserved ejection fraction (HFpEF) remains poorly understood.

Purpose
The present study aims to study the role and mechanism of omentin-1 in cardiac function and myocardial cell structure in HFpEF.

Methods and Results
The influences of omentin-1 were investigated in HFpEF mice (HFD (60% calories from lard) and L-NAME (0.5 g/L in drinking water)), which were treated in vivo. Echocardiography showed better diastolic function in HFpEF mice treated with omentin-1 (5 ug/kg/h) subcutaneously for 4 weeks, and tissue staining showed alleviated myocardial fibrosis and myocardial hypertrophy. The RNA sequencing analysis revealed variations in the gene expression related to ketone body metabolism in HFpEF mice after omentin-1 treatment (600 ng/ml). The supernatant was obtained from mouse bone marrow macrophages treated with ultrapure endotoxin and ATP and was utilized as the macrophage-conditioned medium for culturing primary cardiomyocytes, which were stimulated with isoproterenol for 48 hours to construct the HFpEF cardiomyocyte model. In the heart tissue of HFpEF mice and HFpEF cardiomyocytes treated with omentin-1, there was a notable increase in the expression of a pivotal enzyme of ketone body metabolism- succinyl-CoA transferase (SCOT), and a decrease in the expression of hypertrophy signal. The myocardial hypertrophy model was established by stimulating the myocardial cell line H9C2 with isoproterenol. Following the inhibition of the integrin receptor and PI3K-AKT pathway, the impacts of omentin-1 on SCOT and myocardial hypertrophy signal expression in hypertrophic cardiomyocytes were eliminated.

Conclusion
This study provides evidence for the effects of omentin-1 on cardiac function and myocardial structure in HFpEF and proposes that omentin-1 may stimulate the downstream PI3K/AKT pathway via integrin receptors on cardiomyocytes, leading to increased expression of SCOT and improvement of cardiomyocyte hypertrophy.
Biomarkers for monitoring patients with cardiac amyloidosis during transthyretin-stabilizer therapy
Authors: Vogel J , Jura S , Buehing F , Wernhart S , Carpinteiro A , Rassaf T , Michel L 
Published: October 2024

Abstract

Introduction
Cardiac amyloidosis is characterized by deposition of amyloid fibrils in the heart, leading to structural abnormalities and functional impairments resulting in heart failure. Amyloid transthyretin amyloidosis cardiomyopathy (ATTR-CM) is the most common form with increasing incidence due to growing awareness and improved diagnosis. The ATTR stabilizer tafamidis serves as the first specific therapy approved for ATTR-CM, and many promising substances are in late-stage clinical trials. With growing numbers of patients receiving stabilizer therapy, valid tools for monitoring treatment response and detecting disease progression are currently lacking. Here, we aim to assess systemic and cardiac biomarkers in patients receiving stabilizer therapy.

Method
All individuals diagnosed with ATTR-CM at our university hospital, were systematically assessed for eligibility in this study. We enrolled patients who were undergoing therapy with tafamidis. Biomarkers including Hemoglobin (Hb), Creatinine, estimated glomerular filtration rate (eGFR), International Normalized Ratio (INR), C-reactive protein (CRP), Troponin and NT-proBNP were examined at baseline and during 6 and 12 months follow-up. Wilcoxon signed rank test was used for statistical analysis. The study was approved by the local ethics committee (23-11500-BO).

Results
194 patients were included in the analysis with median age of 80 (76-83) years (86,6% male). Results showed an impaired renal function at baseline (all mean ± SD) with creatinine 1.24 ± 0.46 mg/dl and eGFR 58.64 ± 18.24 ml/min/kg with statistically significant increase after 6 months in creatinine (1.31 ± 0.51 mg/dl, p&lt;0.001) and eGFR (55.06 ± 17.65 ml/min/kg, p&lt;0.001) and after 12 months (creatinine 1.35 ± 0.54 mg/dl, p&lt;0.001, eGFR 53.27 ± 17.68 ml/min/kg, p&lt;0.001). Hb showed a significant increase after 6 (13.61 ± 1.78 g/dl, p&lt;0.001) and 12 months (13.6 ± 1.79 g/dl, p&lt;0.001), compared to baseline (13.41 ± 1.71 g/dl, p&lt;0.001). Comparison of baseline values for CRP (0.08 ± 1.18 mg/dl), Troponin (86.33 ± 190.6 ng/l), NT-pro BNP (4703 ± 4385 pg/ml) and INR (1.25 ± 0.46) after 6 (CRP p=0.28, Troponin p=0.7, NT-pro BNP p=0.97, INR p=0.91) and 12 months (CRP p=0.12, Troponin p=0.59, NT-pro BNP p=0.78, INR p=0.28) showed no significant changes.

Conclusion
Although troponin and BNP are routinely used and recommended as biomarker for monitoring patients with ATTR-CM, the diagnostic value may be insufficient to assess therapy response. Results emphasize the need to identify new biomarkers to adequately reflect the specific aspects of ATTR-CM disease progression. This study reveals significant alterations in creatinine and eGFR due to a worsening of kidney function, but an increase of Hb, suggesting a potential indicator for treatment response. Future research should explore innovative approaches like proteomic analysis as promising approach for both diagnostic and prognostic biomarkers.
Patient journey from the appearance of red flags to the diagnosis of transthyretin cardiac amyloidosis (ATTR-CM) in Japan: a nationwide retrospective study using a medical claims database
Authors: Minamisawa M , Konishi H , Kitano Y , Abe H , Togo K , Izumiya Y 
Published: October 2024

Abstract

Introduction
Transthyretin amyloid cardiomyopathy (ATTR-CM) is an under-recognized cause of common cardiovascular conditions in the elderly, with relatively high rates among patients diagnosed with heart failure (HF) with preserved ejection fraction. In addition to cardiac symptoms such as HF, extracardiac symptoms such as carpal tunnel syndrome (CTS) and lumbar spinal stenosis (LSS) are also red flags for ATTR-CM. Tafamidis is currently the only disease-modifying therapy approved for the treatment of patients with ATTR-CM and is likely to be more effective in the earlier stage. Patients with ATTR-CM often undergo a long and difficult diagnostic journey because of the nonspecificity of clinical manifestations, resulting in delays in establishing the correct diagnosis.

Purpose
To identify the timing of appearance of comorbidities in patients with ATTR-CM during diagnosis.

Methods
In this retrospective, non-interventional, observational study using a claims database (dataset period: April 1, 2014–August 31, 2021), adult patients with a diagnosis of ATTR-CM or prescription for tafamidis 80 mg were included. The index date was defined as the first date of recording ATTR-CM diagnosis or the prescription of tafamidis 80 mg, whichever was earlier. The baseline period was defined as the period between the index date and 6 months before the index date. The onset date was defined as the first date of recording diagnosis of the first red-flags that was suspicious for ATTR-CM.

Results
Of 11,101,578 patients in the database, 246 patients with ATTR-CM met the inclusion criteria. A total of 239 patients were included, of whom 139 had received tafamidis 80 mg. The median (range) age at the index date was 79.0 (46.0–95.0) years, and 79.9% (191/239) were male. The most frequently reported comorbidity defined as onset of ATTR-CM was conduction disorders (88.7%) followed by atrial fibrillation/atrial flutter (50.6%), hypertensive heart disease (19.7%), aortic stenosis (15.9%), and hypertrophic cardiomyopathy (11.7%), with the median (interquartile range [IQR]) time to the index date being 15.5 (5.0–24.5), 14.0 (5.0–22.0), 9.0 (2.0–18.0), 5.0 (2.0–16.0), and 12.0 (6.5–21.5) months, respectively (Fig. 1). LSS (23.9%), neuropathy (13.0%), and CTS (7.5%) were frequently observed as extracardiac symptoms at baseline, and the median (IQR) time from appearance to the index date was 19 (9.0–28.0), 5.0 (1.0–16.0), and 18.0 (14.0–25.0) months, respectively (Fig. 2).

Conclusions
This study elucidated the time lag between the appearance of cardiac and extracardiac complications of ATTR-CM and its diagnosis in real-world clinical settings. These novel findings highlight the potential for earlier detection of ATTR-CM.