bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delays in diagnosis and treatment initiation of ATTR cardiac amyloidosis: a real-world data analysis
Authors: Vogel J , Jura S , Buehing F , Wernhart S , Carpinteiro A , Rassaf T , Michel L 
Published: October 2024

Abstract

Introduction
Cardiac amyloidosis (CA) is a serious condition characterized by the accumulation of abnormal protein deposits in the heart muscle, leading to functional impairments and, ultimately, heart failure. Transthyretin amyloid cardiomyopathy (ATTR-CM) is the most common form encountered in CA diagnosis with previously underestimated prevalence. ATTR-CM poses a diagnostic challenge, with a substantial number of cases diagnosed late and at advanced stages. The availability of specific pharmacological treatment using the transthyretin-stabilizer tafamidis further emphasizes the need for timely diagnosis. Here, we aim to assess delays in diagnosis and initiation of therapy in a real-world collective of patients with ATTR-CM.

Methods
All individuals diagnosed from 01/2018 to 05/2023 with ATTR-CM at our university hospital, Germany, were systematically assessed for eligibility in this study. Specifically, we enrolled patients who were undergoing transthyretin stabilizer therapy. The investigation aimed to determine the duration, in days, from the initial suspicion of heart disease to the definitive diagnosis of ATTR-CM. It was also investigated whether the diagnosis of ATTR-CM was made more quickly over time as awareness increased. Additionally, the study assessed the time elapsed until patients received pharmacological therapy following the confirmed diagnosis. The study was approved by the local ethics committee (23-11500-BO).

Results
After screening of 194 consecutive patients, 154 were included in the analysis, while 40 patients were excluded due to insufficient records. The results of this study reveal that a median of 300 (113-962) days elapsed from the initial suspicion of amyloidosis to the final confirmation. Initial indications of CA often presented as nonspecific symptoms such as unclear dyspnea (16.2% n=25), abnormal echocardiography (75.3% n=116), or, in rare cases, incidental findings (8.4% n=13). Following the diagnosis, an additional median of 84 (46-163.5) days passed before the first prescription of a transthyretin stabilizer. To assess an improvement of ATTR-CM diagnosis over time, we stratified the data into tertiles by date of first diagnosis. The results showed a gradually decrease in medium time to diagnosis of 466 (181-1035) days in the earliest tertile (2018-2019) to 389 (141-1508) days in the most recent tertile (2022-2023) (p&lt;0.001).

Conclusion
This study shows a major healthcare deficit and underscores the medical need for improved screening procedures and diagnostic modalities to expedite the timely diagnosis of CA, as early identification of the condition is crucial for enhancing the quality of life for patients and preventing life-threatening complications.
Prognostic impact of left atrial reverse remodeling in patients with ADHF-HFpEF regardless of atrial fibrillation -PURSUIT-HFpEF Registry-
Authors: Kondo T , Watanabe T , Yamada T , Seo M , Yano M , Hayashi T , Nakagawa A , Nakagawa Y , Yasumura Y , Sotomi Y , Hikoso S , Okada K , Nakatani D , Fukunami M , Sakata Y 
Published: October 2024

Abstract

Background
Left atrial (LA) dilatation is associated with increased mortality in patients with cardiovascular disease including heart failure (HF) and LA reverse remodeling (LARR) was reported to be associated with favorable outcomes in patients with HF. However, it remains to be clarified whether LARR could have prognostic value in patients with HF with preserved ejection fraction (HFpEF).

Purpose
The purpose of this study is to elucidate whether LARR is associated with clinical outcome in patients with HFpEF in relation to the presence of atrial fibrillation (AF).

Methods
We prospectively studied 492 patients with acute decompensated heart failure with preserved ejection fraction (ADHF-HFpEF) without the poor outcome during the first year postdischarge. Echocardiography was performed just before discharge and at 1 year after discharge. LARR was defined as the reduction of 15% or more in left atrial end-systolic volume (LAV). The primary outcome was rehospitalization for worsening heart failure.

Results
All study patients were divided into 2 groups according to the presence of AF at discharge (AF group, n=182 and non-AF group, n=310). During a mean follow-up period of 1.4±1.2 years, 78 patients were rehospitalized for worsening heart failure (37 patients in AF group and 41 in non-AF group). ΔLAV, the degree of reduction in LAV during the first year postdischarge, was significantly independently associated with primary outcome after multivariable adjustment both in AF group (p=0.033, HR 0.992 [0.984-0.999]) and non-AF group (p=0.021, HR 0.986 [0.974-0.998]). Kaplan-Meier analysis revealed that patients with LARR had significantly lower risk for primary outcome than those without LARR not only in the whole study patients (8% vs 20%, p=0.001) but also both in AF group (9% vs 24% p=0.013) and in non-AF group (8% vs 16% p=0.043). Among clinical characteristics during the index hospitalization, the presence of AF and prior HF hospitalization were significantly independently associated with LARR at multivariate Cox logistic regression analysis (p=0.006, OR 0.554 [0.364-0.843] and p=0.007, OR 0.491 [0.292-0.826], respectively).

Conclusion(s)
The left atrial reverse remodeling could have the prognostic impact in patients with ADHF-HFpEF regardless of the presence of atrial fibrillation.Kaplan-Meier curves in AF and non-AF
Gradual hypertensive response in aortic alterations and myocardial inflammatory activation in progressing HFpEF in mice
Authors: Torma D , Rinta-Harri M , Ruotsalainen A K , Yla-Herttuala S 
Published: October 2024

Abstract

Introduction
Hypertension is the most common comorbidity in patients affected by heart failure with preserved ejection fraction (HFpEF). Early effects of pressure overload and its contribution to the gradual development of cardiac and vascular pathology leading to HFpEF are not well recognized, as patients are diagnosed when the disease has already advanced and show symptoms. Several hypertensive HFpEF mouse models possessing the hallmarks of the clinical-like phenotype are available. Nonetheless, initial and gradual pathological manifestations of hypertensive HFpEF have not been comprehensively described.

Purpose
This study aimed to investigate the gradual progression of HFpEF phenotype development in mice from the early manifestation of cardiac and vascular pathology to global cardiac dysfunction to multiorgan syndrome in response to hypertension.

Methods
Hypertensive HFpEF was induced by angiotensin II infusion in C57BL/6JOlaHsd 18-20-week-old male mice that were given low, moderate and high doses (0.5mg/kg/day - 1.5 mg/kg/day) subcutaneously for 4 weeks. Cardiac physiology and alterations in haemodynamics were assessed with echocardiography of heart and aorta, weekly ECG monitoring, and blood pressure measurements from the mouse tail. Extensive histology and immunohistochemistry analyses of cardiac tissue, microvasculature, lungs and kidneys were performed.

Results
In the low dose group, loss of aortic wall flexibility and presence of aortic root dilatation were detected. This group also demonstrated initiation of concentric remodelling process with the upsurge in macrophage infiltration in myocardium, but the signs of diastolic dysfunction were not yet present. The high dose group exhibited characteristic HFpEF features with diastolic dysfunction, left ventricular hypertrophy and fibrosis. Pathology in cardiac conduction system was noticed in all groups, with prominent ECG waveform abnormalities already on week one. However, only the high dose group experienced non-recovery in impulse propagation, accompanied by significant prolongation of ventricular depolarization.

Conclusion
This study demonstrates that change in aortic root dimensions and aortic wall dynamics are the first hypertension-sensitive alterations together with myocardial inflammatory cell infiltration that may contribute to myocardial remodelling and subsequent development of HFpEF and systemic effects. Hypertensive angiotensin II-induced HFpEF is a relevant mouse model, recapitulating not only hallmarks of cardiac pathology but also an extensive range of vascular and multiorgan alterations, demonstrating similarities with the clinical phenotype.
Differences in the optimization of pharmacological treatment in patients with heart failure and reduced ejection fraction and advanced chronic kidney disease
Authors: Recio Mayoral A , Anguita Gamez M , Gonzalez Manzanares R , Muniz Garcia J , Elola Somoza F J , Bonilla Palomas J L , Cequier Fillat A , Romero Rodriguez N , Rodriguez Padial L , Anguita Sanchez M 
Published: October 2024

Abstract

Introduction
Chronic kidney disease is very prevalent in patients with HF, makes their treatment difficult and worsens their prognosis, especially when it is advanced CKD (glomerular filtration rate &lt;30 mL/min/m2). Renal insufficiency increases the risk of drug intolerance and an increase in serious side effects, which can lead to underuse, with consequent negative effects on patient prognosis.

Purpose
To analyze in a contemporary registry of HF patients followed in specialized HF units in Spain the achievement of dose targets for the most used drugs in HF with reduced ejection fraction (HFrEF) and the impact of advanced CKD.

Methods
We analyzed 914 patients with HFrEF consecutively included between 2019 and 2021 in the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology in 45 centers. We evaluated the proportion of patients treated with ACEI, ARA, ARNI, MRA, beta-blockers and SGLT2 inhibitors at the registry inclusion visit, the causes of non-prescription, and the achievement of the maximum dose recommended in the ESC clinical practice guidelines or the maximum tolerated dose in these patients, comparing the GFR groups, greater or less than 30 ml/min/m2.

Results
Of the 914 patients, 8.9% had a GFR&lt;30 mL/min/m2. Their age was 76.9±9.7 years, 39.7% women, mean LVEF 32.8±9-6%. Patients with GFR&lt;30 received in a significantly lower proportion all HF drugs except diuretics, ARBs and potassium chelators: sacubitril-valsartan 30.5% vs 59.2%; MRAs 31.7 vs 77.8%; SGLT2 inhibitors 34.1 vs 52.9% (p&lt;0.001; Figure 1). The main reason for non-use was intolerance/contraindication for beta-blockers and "other" for the rest of the drugs (Figure 1). The proportion of patients in whom the maximum recommended, or maximum tolerated dose was reached was low in both groups, less than 40-50% for all drugs except MRA. There were no significant differences between the two groups in relation to the degree of renal dysfunction, although there was a tendency for the recommended doses to be obtained more frequently in the group with lower GFR (Figure 2).

Conclusions
In our contemporary cohort of real-life patients with HFrEF and advanced CKD, the use of recommended drugs for HF was significantly lower than in those patients with better renal function. However, where they were used, maximum recommended or tolerated doses were achieved in a higher proportion of patients. This indicates that with adequate selection it is possible to achieve the objectives proposed by the clinical practice guidelines in this complex group of patients.
Survival benefit of guideline-directed medical therapy in elderly patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis
Authors: Tan E , Chan M W , Li F , Ho V W T , Lin W Q , Yeo T C , Chai P , Wong R , Kong W , Sia C H 
Published: October 2024

Abstract

Background
Heart failure is a major cause of mortality in the elderly and heart failure-related mortality in elderly patients has increased since 2012. The evidence of guideline-directed medical therapy (GDMT), the four pillars of treatment of heart failure with reduced ejection fraction (HFrEF), remains insufficient in this population.

Aim
The objective of this study was to assess the survival benefit of the four pillars of GDMT in elderly patients aged ≥ 65-years-old with HFrEF.

Methods
MEDLINE, EMBASE and the Cochrane Library were searched from inception to 21 July 2023. The inclusion criteria were studies comparing survival between patients ≥ 65-years-old with left ventricular systolic dysfunction receiving and not receiving GDMT. Pooled prevalence, hazard ratio (HR) and risk ratio (RR) were calculated with 95% confidence interval (CI). Heterogeneity was explored through subgroup analyses based on the number of GDMT, age cut-off, sample size, ejection fraction cut-off, study type and study publication date.

Results
Thirty studies with 86,941 patients from 1994 to 2019 were included. The GDMT group received three drug classes in three studies, two drug classes in four studies, and at least one class in the remaining studies. There were no reported studies on elderly patients receiving four classes of GDMT. Over 5% of the elderly HFrEF patients were frail (Pooled prevelance 7%, 95%CI 2.0–14.0, I2 98%). Frail elderly patients were less likely to receive GDMT (RR 0.63, 95%CI 0.45–0.89, I2 50%, p = 0.009). There was a survival benefit of GDMT in elderly patients with HFrEF (HR 0.70, 95%CI 0.65-0.76, I2 75%, p &lt; 0.001). Elderly patients receiving BB were more likely to develop bradycardia (RR 3.96, 95%CI 2.71-5.80, p &lt; 0.001, I2 0%). There was no difference in the incidence of hypotension, acute renal impairment, and hypoglycemia between the GDMT and control group. The funnel plot appeared asymmetrical which suggests possible publication bias.

Conclusion
The use of GDMT in elderly HFrEF patients was associated with a survival benefit. Frailty may interfere with the implementation of GDMT. High quality studies are needed to guide the safety and efficacy of GDMT, and the development of guidelines on HFrEF management the in elderly according to frailty status.Forrest plot of overall survival
The predisposing factors to heart failure diagnosis and early mortality among young adults in Africa: a narrative review
Authors: Mohammed F , Potter H 
Published: October 2024

Abstract

Introduction
Heart failure (HF) is a major health concern mainly diagnosed among elderly individuals. Primarily, researchers have focused on this age group, nevertheless, compared to individuals from other regions of the world, Africans presents with HF two decades sooner (52 versus 79 years). Even though it manifests early, young persons (18–35 years old) are also diagnosed with HF with prognoses comparable to the older group. Less is known about how much study is concentrated on this age range, although globally, young adults of African origin make up the majority of those with an early onset of heart failure. Additionally, obtaining information about how HF impacts African youth remains challenging.

Purpose
To determine the cause of Africans' early HF diagnosis as well as the risk factors for HF diagnosis and early mortality among young adults.

Methodology
Three electronic databases— MEDLINE Ovid, Scopus, and CINAHL Plus—were searched using the Boolean operators. The first retrieved hits were checked for relevancy by titles and abstracts. Then, publications were fully screened for inclusion in the review based on the pre-established criteria. Also, reference lists of the articles were snowballed for pertinent studies. The scientific integrity of the studies was evaluated using a guided, in-depth peer-reviewed article on how to critically analyse clinical research and the Critical Appraisal Skill Programme (CASP) tool cohort checklist. Pertinent information regarding the study was analysed using a narrative review methodology. Eleven (11) articles out of the 135 pulled from the databases met the requirements for inclusion in the review after a thorough screening. One article was eliminated upon critical evaluation of the research's methodology, and an eligible article was discovered from snowballing reference lists. Therefore, only 11 articles qualified for this review study.

Results
Findings from the review show that HF is diagnosed earlier among Africans due to the early presentation of the major causes of HF before the age of 30 years. Rheumatic heart disease, cardiomyopathy, ischemic heart disease, HTN, and pulmonary illnesses (COPD, TB, and pulmonary arterial hypertension) are known aetiologies. More so, young adults who are diabetic, obese, have hyperlipidaemia or smoke cigarettes are more likely to develop HF. Furthermore, socioeconomic status, alcohol use, smoking, renal dysfunction, higher serum levels of brain natriuretic peptide (BNP) and creatine kinase (Isomer MB), cardiogenic shock, and decreased ejection fraction were the predictors of death with significant p-values (0.05).

Conclusion
Although HF affects young African adults disproportionately causing them to live lower quality of life and shorter lives, no research before this has been conducted. Therefore, further study is required to understand how HF affects this target age range (18 to 35 years) and to develop a long-term plan to fight this illness before it worsens.
Prognostic implications of genotype findings in non-ischemic dilated cardiomyopathy: a network meta-analysis
Authors: Anastasiou V , Papazoglou A S P , Gossios T G , Zegkos T Z , Daios S D , Moysidis D V M , Koutsiouroumpa O K , Parcharidou D P , Tziomalos G T , Katranas S K , Rouskas P R , Karamitsos T K , Ziakas A Z , Kamperidis V K , Efthimiadis G K E 
Published: October 2024

Abstract

Background
Evidence on the relative impact of diverse genetic backgrounds associated with non-ischemic dilated cardiomyopathy (DCM) remains contradictory.

Aim
This study sought to synthesize the available data regarding long-term outcomes of different gene groups in DCM.

Methods
Electronic databases were systematically screened to identify studies reporting prognostic data on pre-specified gene groups. Those included pathogenic/likely pathogenic (P/LP) variants, truncating titin variants (TTNtv), lamin A/C mutations (LMNA), and desmosomal proteins. Outcomes were divided into composite adverse events (CAEs), major ventricular arrhythmic events (MVAEs) and heart failure events (HFEs). Random effects meta-analyses were conducted to quantify the pooled odds ratio (ORs) for each gene group. A frequentist network meta-analysis was executed to allow indirect within-gene group comparisons.

Results
Twenty-six studies comprising 7,255 genotyped DCM individuals were included. Patients with P/PL variants had a higher risk for CAEs [OR, 2.10 (95% CI, 1.67-2.65)], MVAEs [OR, 1.86 (95% CI, 1.52-2.26)], and HFEs [OR, 2.01 (95% CI, 1.08-3.73)] than genotype negative patients. The presence of TTNtv was linked to a higher risk for CAEs [OR, 1.78 (95% CI, 1.20-2.63)], but not MVAEs or HFEs. LMNA and desmosomal groups suffered a higher risk for CAEs, MVAEs, and HFEs compared to non-LMNA and non-desmosomal groups respectively (Picture 1). When genes were indirectly compared, the presence of LMNA resulted in a more detrimental effect that TTNtv, with respect to all composite outcomes but no significant difference was found between LMNA and desmosomal genes. Desmosomal genes harbored a higher risk for MVAEs compared to TTNtv (Picture 2).

Conclusion
Different genetic substrates associated with DCM result in divergent natural histories. Routine utilization of genetic testing should be employed to refine risk stratification and inform therapeutic strategies in DCM.Natural history of DCM based on genotypeNetwork meta-analysis of gene variants
Real-world evidence for patient phenotypes in heart failure with preserved ejection fraction
Authors: Balitzki J , Schaper S , Roessig L , Sandner P , Thum T , Bauersachs J , Mondritzki T 
Published: October 2024

Abstract

Background
Heart failure (HF) with preserved ejection fraction (HFpEF) presents a high mortality risk due to its heterogeneous and multifactorial nature, coupled with limited treatment options. The incompletely understood pathophysiology is influenced by various comorbidities, resulting in different clinical phenotypes. Identifying these could be crucial for tailored HFpEF treatments. While previous studies focused on small, well-characterized patient populations, electronic health records (EHRs) offer the potential to unveil HFpEF phenotypes in larger real-world patient groups.

Purpose
We aimed to establish a sizable, unselected HFpEF patient population using real-world data. Employing cluster analysis, we intended to uncover distinct groups with varied disease aetiology and medical needs based on comorbidity profiles and prognoses.

Methods
From EHRs of n = 1,610,101 HF patients, we identified an HFpEF cohort of n = 32,009 patients, by applying thresholds for the LVEF and data availability, and by excluding confounding conditions. Clustering by the relative frequency of common comorbidities aimed to reveal patient populations with unique prognoses, comorbidity profiles, and clinical and demographic characteristics.

Results
Six clusters of different sizes, comorbidity prevalence, clinical presentation, and all-cause mortality were identified. About 50% of patients (n = 15,445) were predominantly hypertensive, with varying extents of coronary heart disease and diabetes mellitus (DM), and a 5-year mortality of about 30%. Around 22% (n = 7,089) exhibited a cardiometabolic comorbidity profile, with an increased prevalence of obesity and sleep apnea, but also DM and hypertension, and a 5-year mortality of 22.5%. Over 15% of patients (n = 5,298) had a 5-year mortality rate of 45.0%, marked by highest rates of anaemia and chronic kidney disease (CKD) but also DM, elevated N-terminal prohormone of brain natriuretic peptide levels, and a reduced estimated glomerular filtration rate.

Conclusion
Despite the favourable prognosis, a significant proportion of patients represent a cardiometabolic HFpEF phenotype with notable unmet medical needs regarding cohort size and multimorbidity. Patients simultaneously suffering from CKD, anaemia, and the highest mortality rates may represent a previously underrecognized phenotype. Our study demonstrates that distinct medical needs can be identified in a large, unselected real-world HFpEF cohort. In contrast to clinical trials, this approach enabled access to a broader patient population, revealing novel phenotypes to be targeted by precision medicine in the future.