bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cysteine-rich angiogenic inducer 61 (CCN1) independently predicts all-cause mortality in patients with dilated cardiomyopathy
Authors: Klingenberg R , Gross S , Lehnert K , Wegner D , Hamm C.W , Felix S , Keller T , Doerr M 
Published: October 2021

Abstract

Introduction
Cysteine-rich angiogenic inducer 61 (Cyr61, CCN1) is a member of the CCN family of matricellular proteins exerting key functions in inflammation and fibrotic turnover. Recently it has been shown that CCN1 improves risk stratification for all-cause mortality in ACS patients.

Purpose
Since both inflammation and fibrosis are key processes involved in the pathogenesis of dilated cardiomyopathy (DCM), we aimed to investigate the prognostic value of CCN1 serum levels for survival in a large cohort of DCM patients.

Methods
The cohort compromised patients with a primary diagnosis of DCM, defined as a reduced left ventricular ejection fraction (LVEF &lt;45%) and an increased left ventricular enddiastolic diameter according to the HENRY score (LVEDD according to HENRY &gt;117%) at the time of diagnosis. Exclusion criteria were primary valvular diseases (≥ second degree), acute myocarditis, active infectious diseases, pulmonary diseases, cancer, chronic alcoholism and heart failure of other origins. CCN1 levels were determined in human serum using an enzyme-linked immunosorbent assay (R&D Systems, USA). Multivariable cox regression models for the association between CCN1 and all-cause mortality were adjusted for age, sex, disease duration, LVEF, estimated glomerular filtration rate (eGFR) measured based on the CKD-EPI formula, high-sensitivity C-reactive protein (hs-CRP) and aminoterminal-proB-type natriuretic peptide (NT-proBNP) levels.

Results
306 DCM patients had available biomarker and clinico-demographic data in this single-center cohort (79.3% males) with a mean age of 55.2 years [interquartile range [IQR] 47.9, 64.8]). On average, disease duration was 0.3 years (IQR 0.9, 1.9), LVEF 31% (IQR 25, 37), LVEDD 67.7 mm (IQR 63, 72), and eGFR 91.5 ml/min (IQR 74.1, 102.4). During a median follow-up of 12.5 years (IQR 10.5, 14.1), a total of 114 (37.3%) patients died. Multivariable-adjusted cox regression models revealed an increasing all-cause mortality risk across CCN1 tertiles (p for trend = 0.03), with the highest incidence in the highest tertile (hazard ratio [HR] 1.75; 95%-CI 1.04, 2.94; P=0.034) as compared to the lowest tertile (Figure 1).

Conclusion
CCN1 predicts long-term survival in DCM patients independent of NT-pro-BNP and other risk determinants. Further research needs to evaluate whether this novel biomarker also plays a causal role in the pathogenesis of DCM.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Kerckhoff Foundation Figure 1
Reassessing the NYHA classification for heart failure: a comparison between classes I and II using cardiopulmonary exercise testing
Authors: Zimerman A , Cardoso De Souza G , Engster P , Spier Borges M , Ulrich Schaan T , Pilar I , Stein R , Fonteles Ritt L.E , Donelli Da Silveira A , Rohde L.E 
Published: October 2021

Abstract

Background
The New York Heart Association (NYHA) functional classification has evolved to become a major determinant of eligibility to medical interventions and clinical trials, but its reliability to discriminate patients with mild heart failure (HF) has been questioned by studies that demonstrated a major overlap in self-reported symptoms and laboratory markers between NYHA classes I and II.

Purpose
To assess the reliability of NYHA classification by comparing cardio-pulmonary exercise test (CPET) results and its overlap between HF patients classified as NYHA I and II.

Methods
We retrospectively analyzed data from HF patients who underwent CPET in 3 medical centers in Brazil. NYHA class was defined as recorded on CPET day or during the previous clinical visit. Inclusion criteria were diagnosis of HF, age ≥16, and NYHA class I or II. We analyzed overlap between kernel density estimations for the percent-predicted peak VO2, minute ventilation/carbon dioxide production (VE/VCO2) slope, and oxygen uptake efficiency slope (OUES) in patients in NYHA classes I and II. Categorical variables were compared using chi-square tests.

Results
We included 684 patients, of which 42% (284) were classified as NYHA I. Mean age was 56.1 years; 44% (303) were female and mean left ventricular ejection fraction was 36% (±14.2%). Regarding CPET measures, mean global percent-predicted peak VO2 was 56.6% (±26.1%), VE/VCO2 slope was 38.8 (±10.2), and OUES was 1.50 (±0.59). Kernel density overlap between NYHA classes I and II was considerable: 83% for percent-predicted peak VO2, 89% for VE/VCO2 slope, and 85% for OUES (Figure 1). There was no significant difference between NHYA I and II in CPET indicators of poor prognosis: percent-predicted peak VO2 &lt;50% was present in 53% vs. 48% of patients classified as NYHA I and II, respectively (p=0.15); VE/VCO2 slope &gt;36 in 54% vs. 57% (p=0.39); and OUES &lt;1.4 in 46% vs. 48% (p=0.51).

Conclusions
HF patients classified as NYHA I and II overlap substantially in objective measures of functional capacity assessed by CPET. These findings suggest that NYHA classification is a poor discriminator of cardiopulmonary capacity among patients with mild HF, and raise questions about its use as a benchmark to guide HF therapy.

Funding Acknowledgement
Type of funding sources: None. Figure 1
Comparison of one-year survival prediction tools in patients with advanced heart failure
Authors: Blum M , McKendrick K , Gelfman L.P , Goldstein N.E 
Published: October 2021

Abstract

Background
Predicting survival in patients with advanced heart failure (HF) remains difficult and prognostic scores such as the Seattle Heart Failure Model (SHFM) are cumbersome to use. Alternative approaches like the Surprise Question (SC) or the number of HF hospitalisations within the last year (NoH) could simplify prognostication.

Purpose
We assessed the prognostic utility of the SHFM, SC and NoH for predicting one-year survival status in patients with advanced HF.

Methods
A secondary analysis of a multisite, single-blinded cluster-randomized, controlled trial to test whether a structured intervention of educational content and automated reminders increased the likelihood of ICD deactivation conversations and ICD deactivation. The study was performed within the advanced HF practices at six US academic medical centers, between September 2011 to February 2016. Patient eligibility criteria included advanced HF, an implantable cardiac defibrillator and a high risk of death, with complete data on SHFM, SC, NoH and one-year survival status. SHFM survival was calculated from baseline variables; the SC (“Would you be surprised if the patient were to die within one year?”) was answered by cardiologists; and the NoH was extracted from medical records. For prediction of survival status, cut-offs for predicted survival per SHFM and NoH were chosen empirically by means of receiver operating characteristic (ROC) curve analysis maximising Youden's index. The resulting binary prediction models were assessed based on area under the ROC curve (AUC), sensitivity and specificity.

Results
Of the 535 subjects in our sample, 82 (15.3%) had died after one-year of follow-up. For the SHFM and the NoH, optimal cut-offs were found to be a predicted survival &lt;86% and ≥2 hospitalisations, respectively.
Performance metrics of prognostic models are detailed in Table 1. The SHFM yielded an AUC of 0.65 (0.60–0.71 95% confidence interval [CI]), a sensitivity of 0.76 (0.65–0.84 95% CI), and a specificity of 0.55 (0.50–0.60 95% CI). The SC demonstrated a comparable AUC 0.58 (0.54–0.63 95% CI), similar sensitivity 0.84 (0.74–0.91 95% CI), but lower specificity 0.33 (0.28–0.37 95% CI) compared to the SHFM. The NoH demonstrated a comparable AUC 0.56 (0.50–0.62 95% CI), similar sensitivity 0.56 (0.45–0.67 95% CI), and similar specificity 0.56 (0.51–0.61 95% CI) compared to the SHFM. The combination of positive SC and NoH ≥2 showed significantly higher specificity compared to the SHFM (0.68 [0.64–0.73 95% CI]).

Conclusion
The SC and NoH are clinically feasible bedside alternatives to the more complex SHFM model, yet yield similar overall prognostic utility for one-year survival status among advanced HF patients.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung, and Blood Institute
Age- and Sex-Specific Rates of Heart Failure and other Adverse Cardiovascular Outcomes in Systemic Sclerosis
Authors: Sun G.L , Yafasova A , Andersson C , McMurray J.J.V , Jhund P.S , Docherty K.F , Faurschou M , Nielsen C.T , Shams-Eldin A , Gislason G.H , Torp-Pedersen C , Fosboel E.L , Koeber L , Butt J.H 
Published: October 2021

Abstract

Background
Age at disease onset and sex appear to modify the disease course in patients with systemic sclerosis (SSc). Although patients with SSc have a higher risk of adverse cardiovascular outcomes than people without SSc, there are few data on age- and sex-specific risks of heart failure (HF) and other adverse cardiovascular outcomes in patients with SSc.

Objectives
To investigate the long-term rates of HF and other adverse cardiovascular outcomes (including arrhythmias, myocardial infarction, ischemic stroke, venous thromboembolism, and pulmonary hypertension) in a nationwide cohort of patients with SSc compared with the background population according to age and sex, separately.

Methods
Using Danish nationwide registries, all patients &gt;18 years with newly diagnosed SSc (1996–2018) were identified. SSc patients were matched at a 1:4 ratio by age, sex, and comorbidities with controls from the background population without SSc. Rates of outcomes according to age (above/below median age) and sex were compared between cases and controls using Cox regression.

Results
Of the 2,019 patients diagnosed with SSc, 1,569 patients were matched with 6,276 controls from the background population (median age 55 years, 80.4% women). SSc was associated with a higher rate of HF in both women (HR 2.99 [95% CI, 2.18–4.09]) and men (HR 3.01 [1.83–4.95]) (Pfor interaction=0.88), with similar findings for other cardiovascular outcomes.For age interaction, SSc was associated with an increased rate of HF in patients &lt;55 years (HR 4.14 [2.54–6.74]) and ≥55 years (HR 2.74 [1.98–3.78]), with similar effect of younger and older groups on HF (P for interaction=0.21), and other cardiovascular outcomes.

Conclusions
SSc was associated with an increased long-term rate of cardiovascular outcomes compared with a matched background population, with similar extent in different gender and age groups.

Funding Acknowledgement
Type of funding sources: None. Adjusted hazard ratios according to sexAdjusted hazard ratios according to age
Statin use is associated with lower risk of new onset dementia in patients with heart failure
Authors: Ren Q.W , Yi-Kei T.S.E , Hang-Long L.I , Si-Yeung Y.U , Pui-Fai W.O.N.G , Mei-Zhen W.U , Hung-Fat T.S.E , Kai-Hang Y.I.U 
Published: October 2021

Abstract

Background
Increasing number of heart failure (HF) patients diagnosed with dementia due to improved treatment and aging population. Data relating to the association of statin use on the risk of dementia incidence among patients with HF are sparse.

Methods
Using a previously validated territory-wide clinical information registry, statin use was ascertained among all eligible patients with HF (N=241,995) from 1996 to 2019. Propensity score matching was used to balance baseline covariates between statin nonusers (167,738 patients) with statin users (74,257 patients). Competing risk regression with Cox proportional-hazard models was performed to estimate the risk of incident dementia associated with statin use.

Results
Of all eligible subjects, the mean age was 76.5±13.0 years, 115,371 (47.7%) was male. Over a median follow-up of 2.7 years (interquartile range [IQR]: 0.6 to 6.7), 13,482 (5.6%) patients were diagnosed with dementia including Alzheimer's disease (N=5,253), senile dementia uncomplicated (N=4,273), arteriosclerotic dementia (N=3,262), and others (N=694). Statin use (vs. none) was associated with a 58% lower risk of dementia incidence (multivariable-adjusted sub-distribution hazard ratio [SHR]=0.42; 95% Confidence Interval [CI], 0.38 to 0.46) after accounting for death as a competing risk. Moreover, the male gender was associated with a 51% lower risk of dementia incidence (multivariable-adjusted SHR=0.59; 95% CI (0.54–0.65) compared with females.

Conclusion
Our study suggests that there is substantial sex difference in the incidence of dementia among HF patients. Moreover, statin use is associated with a significantly lower risk of incident dementia in HF.

Funding Acknowledgement
Type of funding sources: None.
Are there predictor variables for the diagnosis of transthyretin cardiac amyloidosis?
Authors: Goena C , Arana X , Villanueva I , Solla I , Rengel A , Querejeta R 
Published: October 2021

Abstract

Introduction
Transthyretin cardiac amyloidosis (ATTR) can be reliably diagnosed in the absence of histology if grade 2 or 3 cardiac uptake is demonstrated on 99mTc-DPD scan (DPD) in the absence of a detectable monoclonal component. Diagnosis requires a high degree of clinical suspicion in the presence of often non-specific findings and that it may be one of the reasons to under-diagnose ATTR. The aim of the study is to identify clinical, analytical and ECG variables that best predict a positive DPD result.

Methods
This is a multicentre retrospective study including all patients undergoing consecutive 99mTc-DPD scintigraphy in a reference area of 750,000 inhabitants between January 2016 and January 2021 for suspected ATTR. AL amyloidosis patients were excluded. Clinical, analytical, ECG and echocardiographic data were analyzed. We identified variables that independently predicted a positive DPD study using a multivariable logistic regression analysis. Receiver Operating Curve (ROC) analysis and the Area under the Curve (AUC) were calculated to assess the discrimination capacity of the model to predict a positive DPD study.

Results
DPD scans from a total of 181 patients were analyzed. Mean age of the sample: 78 years (42–96), 100% caucasians, 77% male. 54.7% (N=99) had a positive DPD study (defined as grade 2 or 3 Perugini uptake) and 45.3% (N=82) were negative. Independent predictors of a positive study were age, male gender, left ventricular septum thickness, any grade of atrioventricular block, low QRS voltage, Carpal tunnel syndrome, history of hypotension or need to lower antihypertensive drugs and a NT-proBNP value above 1800 pg/ml (See Table 1). The diagnostic accuracy of the model was excellent, with an AUC of 0.92 (IC 95% 0.87–0.96) (see Figure 1).

Conclusions
There are clinical-analytical factors and ECG and echocardiogram findings accessible in daily clinical practice that are able to predict a positive result on cardiac scintigraphy requested for suspected ATTR. Identifying these factors may improve the non-invasive diagnosis of ATTR.

Funding Acknowledgement
Type of funding sources: None. Table 1. Multivariable logistic regression analysFigure 1. ROC curve
Long term prognostic value of myocardin expression levels in non-ischemic dilated cardiomyopathy
Authors: Marketou M , Kontaraki J , Patrianakos A , Kanoupakis E , Plevritaki A , Kallergis E , Mavrakis H , Koutalas E , Anastasiou I , Papadaki S , Kochiadakis G , Parthenakis F 
Published: October 2021

Abstract

Background
We The mortality of patients with non-ischemic dilated cardiomyopathy (NIDCM) remains substantial. We evaluated gene expression levels of myocardin, an early cardiac gene, in the peripheral blood cells of NIDCM patients as a prognostic biomarker in their long-term outcome and mortality from congestive HF (CHF).

Methods
We retrospectively analyzed 101 consecutives optimally treated NIDCM patients of Cretan origin who were enrolled from the HF clinic of our hospital from November 2005 to December 2008. Our patient data were either taken from their medical files or recorded during visits to the HF unit or hospitalizations. Follow-up was carried out by telephone interview and by accessing information from general practitioners and cardiologists in private practice.

Results
The median follow up period was 8 years (mean follow-up 7±3.4 years). The overall mortality during follow-up was 61.4%, while mortality due to congestive heart failure (CHF) was 49.5%. Higher CHF and all-cause mortality were observed in patients with myocardin levels &gt;14.26 (p&lt;0.001 for both CHF and all-cause mortality). A multivariate Cox regression analysis showed that myocardin level of expression had independent significant prognostic value for the risk of death from CHF (HR: 14.5, 95% confidence interval (CI): 5.3–39). in those patients.

Conclusions
Peripheral blood cells gene expression of myocardin, an early myocardial marker, may serve as prognostic biomarkers of the long-term outcome of patients with NIDCM. Our findings open new prospects in the risk stratification of these patients.

Funding Acknowledgement
Type of funding sources: None. Figure 1
Low plasma levels of B-type natriuretic peptide predict the insulin resistance and left ventricular concentric remodeling in subjects without heart diseases: the observational arita cohort study
Authors: Okamoto C , Hasegawa T , Tsukamoto O , Hitsumoto T , Matsuoka K , Takashima S , Amaki M , Kanzaki H , Izumi C , Ito S , Kitakaze M 
Published: October 2021

Abstract

Introduction
Although natriuretic peptides (NPs) are established as a biomarker of heart failure (HF), NPs have been attracting attention as a mediator in the metabolic sequences recently. On the other hand, metabolic disorders including insulin resistance have been suggested to be involved in left ventricular (LV) concentric remodeling, hinting us to the unexpected relationship among NPs, insulin resistance and LV concentric remodeling.

Purpose
To investigate whether the basal B-type natriuretic peptide (BNP) level is linked to insulin resistance or LV concentric remodeling in the participants independent of HF in the Japanese Arita-cho cohort study.

Methods
Among 1632 subjects who participated in annual health checks from 2005 to 2008 in Arita-cho, Saga, Japan as a cohort study, we studied 675 subjects without history of cardiovascular disease with LV ejection fraction≥50% and BNP level&lt;35pg/ml (227 men; median 62 years old). Insulin resistance was assessed by homeostatic model assessment of insulin resistance (HOMA-IR) and LV geometry including LV concentric remodeling was classified based on relative wall thickness (RWT) and LV mass index from echocardiographic findings.

Results
The tertile levels of BNP were inversely associated with HOMA-IR (the 1st tertile 1.33 (0.76–1.74), the 2nd tertile 1.05 (0.72–1.59), the 3rd tertile 0.95 (0.66–1.58), p=0.005); in the logistic regression analysis, the lower BNP level was related to the prevalence of insulin resistance defined as HOMA-IR≥1.37 after full multivariate adjustment (1 SD increment of BNP: adjusted odds ratio [aOR] 0.740, 95% confidence interval 0.601–0.912, P=0.005. LV concentric remodeling (RWT &gt;0.42 and LV mass index ≤115 g/m2 in men and ≤95 g/m2 in women) was observed in 170 (25%) subjects; both low BNP level and higher insulin resistance were independently linked with LV concentric remodeling after multivariate adjustment (1 SD increment of BNP: aOR 0.714, 95% CI 0.544–0.938, p=0.015, HOMA-IR≥1.37 vs. &lt;1.37: aOR 1.694, 95% CI 1.004–2.857, p=0.048, respectively) (Figure).

Conclusions
In the cohort without HF, the low BNP level was linked to insulin resistance and LV concentric remodeling independently, suggesting that the subjects with low NPs levels may cause metabolic disorders and LV morphological abnormalities.

Funding Acknowledgement
Type of funding sources: None.
First-phase ejection fraction, a measure of pre-clinical heart failure, is strongly associated with increased mortality in patients with COVID-19
Authors: Gu H , Chiara C , Nabeebaccus A , Sun Z , Fang L , Xie Y , Zhang L , Carr-White G , Shah A , Xie M , Chowienczyk P 
Published: October 2021

Abstract

Introduction
Presence of heart failure is associated with a poor prognosis in patients with COVID-19. The aim of the present study was to examine whether first-phase ejection fraction (EF1), the ejection fraction measured in early systole up to the time of peak aortic velocity, a sensitive measure of pre-clinical heart failure, is associated with survival in patients hospitalised with COVID-19.

Methods
A retrospective outcome study was performed in patients hospitalised with COVID-19 who underwent echocardiography (n=380) at the West Branch of the Union Hospital, Wuhan, China and in patients admitted to King's Health Partners in South London UK. Association of EF1 with survival was performed using Cox proportional hazards regression. EF1 was compared in patients with COVID-19 and in historical controls with similar co-morbidities (n=266) who had undergone echocardiography before the COVID-19 pandemic.

Results
In patients with COVID-19, EF1 was a strong predictor of survival in each patient group (Wuhan and London). In the combined group, EF1 was a stronger predictor of survival than other clinical, laboratory and echocardiographic characteristics including age, co-morbidities and biochemical markers (figure 1). A cut-off value of 25% for EF1 gave a hazard ratio of 5.23 (95% CI: 2.85–9.60, p&lt;0.001) unadjusted and 4.83 (95% CI: 2.35–9.95, p&lt;0.001) when adjusted for demographics, co-morbidities, hs-cTnI and CRP (figure 2). EF1 was similar in patients with and without COVID-19 (23.2±7.3 vs 22.0±7.6%, p=0.092, adjusted for prevalence of risk factors and co-morbidities).

Conclusion
Impaired first-phase ejection fraction is strongly associated with mortality in COVID-19 and probably reflects pre-existing, pre-clinical heart failure.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute for Health Research (NIHR) UKBritish Heart Foundation (BHF) UK Figure 1. ROC curve for prediction of mortalityFigure 2. Kaplan-Meier Curve of EF1 (cut-off 25%)