Class Of Functions Research Articles

Non-invasive assessment of severe liver fibrosis in patients with Fontan-associated liver disease: The VALDIG-EASL FONLIVER cohort

Background & AimsFontan-type surgery is used as a palliation for congenital heart disease with univentricular physiology but may, in the long term, lead to advanced chronic liver disease. This study assessed the accuracy of conventional non-invasive models in assessing liver fibrosis and introduces a new risk score employing non-invasive tools. MethodsA prospective, cross-sectional, observational study was conducted across five European centers and encompassing all consecutive adult patients with Fontan circulation, liver biopsy and non-invasive tests (elastography, APRI, FIB-4, Fibrosis score, Doha, GUCI, and AAR). The primary outcome was the identification of severe liver fibrosis on biopsy. Multivariable logistic regression identified non-invasive predictors of severe fibrosis, leading to the development and internal validation of a new scoring model named the FonLiver risk score. ResultsIn total, 217 patients (mean [standard deviation] age, 27.9 [8.9] years; 50.7% males) were included. Severe liver fibrosis was present in 47.9% (95% CI 41.2%–54.5%) and correlated with a lower functional class, protein-losing enteropathy, and compromised cardiopulmonary and systemic hemodynamics. The final FonLiver risk score incorporated liver stiffness measurement using transient elastography and platelet count and demonstrated strong discrimination and calibration (area under the receiver operating curve [AUROC] of 0.81). The FonLiver risk score outperformed conventional prediction models (APRI, FIB-4, Fibrosis score, Doha, GUCI, and AAR), which all exhibited worse performance in our cohort (AUROC < 0.70 for all). ConclusionSevere liver fibrosis is prevalent in adults following Fontan-type palliation and can be effectively estimated using with the novel FonLiver risk score. This scoring system can be easily incorporated into the routine assessment of patients with Fontan circulation.

Safety and efficacy of riociguat in patients with pulmonary arterial hypertension and cardiometabolic comorbidities: Data from interventional clinical trials

BACKGROUNDThere is limited evidence to support treatment recommendations in patients with pulmonary arterial hypertension (PAH) and comorbidities. To investigate the impact of riociguat treatment in this patient population we analyzed pooled data from randomized controlled trials of riociguat. METHODSThis post hoc analysis included data from the PATENT-1, PATENT-2, PATENT PLUS, and REPLACE studies. Safety, efficacy (6-minute walk distance [6MWD], World Health Organization functional class [WHO-FC], and N-terminal pro-brain natriuretic peptide [NT-proBNP]), and COMPERA 2.0 risk status were assessed in patients with 0, 1–2, or 3–4 cardiometabolic comorbidities (obesity, systemic hypertension, diabetes mellitus, coronary artery disease) in the main phase of the studies. Safety was also assessed in the long-term extensions. RESULTSThe analysis included 686 patients (riociguat, n = 440; placebo, n = 132; phosphodiesterase type 5 inhibitors [PDE5i], n = 114), of whom 55%, 39%, and 6% had 0, 1–2, and 3–4 comorbidities, respectively. In the main phase, rates, and severity of adverse events (AEs) were similar in riociguat-treated patients across comorbidity subgroups. After 2 years, discontinuations of riociguat due to AEs were also similar across subgroups. Compared with placebo and PDE5i, riociguat improved 6MWD and NT-proBNP across comorbidity groups, and improved WHO-FC and COMPERA 2.0 risk status in patients with 0 or 1–2 comorbidities. CONCLUSIONSRiociguat had an acceptable safety profile in PAH patients with cardiometabolic comorbidities. Efficacy and risk assessment results suggest that riociguat can be beneficial for patients with PAH irrespective of the presence of comorbidities.

P105 RENAL DENERVATION WITH SPYRAL SIMPLICITY SYSTEM: A SINGLE CENTER EXPERIENCE IN COLOMBIA

Background and Objectives: Hypertension is the leading cause of death with 10,4 million deaths and 218 disability adjusted life years (DALYs) worldwide in 2017. Despite GDMT, about 10 to 20% of hypertensive subjects will be poorly controlled, meeting the definition for difficult to treat (DTTH) and refractory hypertension (RH). Renal denervation (RDN) with Spyral Simplicity SystemTM has become a promising nonpharmacological treatment for DTTH and RH, and it has shown to be an effective and safe procedure for RH patients in randomized clinical trials with up to 12 months follow-up. Methods: This is a single-center registry including 6 adults with DTTH and RH confirmed by ABPM and without secondary hypertension, underwent RDN in a tertiary hospital in Bucaramanga, Colombia. A 6-months follow-up was performed, recording clinical data (symptoms, NYHA functional class, number and type of antihypertensive medications, heart rate and ER visits) and paraclinical tests (ABPM, eGFR and echocardiogram). Results: Mean age was 73 ± 4,64 years-old with 50% females. Main comorbidities were dyslipidemia (100%), cardiovascular disease (100%), and type 2 diabetes (83,3%). Pre-procedural medication average was 5. All patients were in NYHA II, with preserved left ventricular EF and mild to moderate diastolic disfunction. At 6 months of follow-up, there was a mean reduction in systolic blood pressure (SBP) of 10 mmHg (145 to 135 mmHg) in ABPM and 26 mmHg (169 to 143 mmHg) in office. There were not significant changes between pre- and post-procedural mean HR (68 vs. 61 bpm), neither short- or long-term complications associated with the procedure. In average, one drug withdrawal was observed. All the subjects improved their NYHA functional class. There were no ER visits in the 6-month follow-up. Conclusions: RDN is effective and safe for patients with DTTH and RH, achieving significant reduction in ABPM and office SBP, reducing medication number, improving NYHA functional class and avoiding visits to ER in the mid-term follow-up.

Investigation of the effects of polyethylene microplastics at environmentally relevant concentrations on the plant-soil-microbiota system: A two-year field trial

Microplastics are a potential threat to agricultural sustainability. However, the effects of microplastics at environmentally relevant concentrations on the plant-soil-microbiota system in realistic field conditions are largely unknown. Herein, we conducted a two-year field trial to study the effects of polyethylene (PE) microplastics at 0, 100, and 600 mg/kg on crop growth, soil properties, and the composition and function of microbial communities in a farmland with rice-wheat rotation. PE did not affect wheat growth but it increased the rice grain weight by 42.5 % at 600 mg/kg, and enhanced rice height by 35.4 % and 30.2 % at 100 and 600 mg/kg, respectively. The presence of PE significantly decreased soil available phosphorus during the wheat season, while it reduced soil total nitrogen, NH4+-N and available phosphorus during the rice season. There were five and sixteen bacterial orders identified changed by PE in wheat and rice soils, respectively. Specifically, PE at different concentrations differentially altered the abundances of sulfate-reducing bacteria Thermodesulfovibrionia, Thermoactinomycetales and Syntrophobacterales, and further modified soil sulfate respiration in wheat soils. During the rice season, PE (100 mg/kg) increased the abundance of Xanthomonadales by 98.0 % and enriched the functional groups of intracellular parasites, while PE (600 mg/kg) inhibited twelve cluster of orthologous group function classes and disturbed bacterial metabolism. This study suggests that PE exhibits a greater impact on the plant-soil-microbiota system during the rice season compared to the previous year's wheat season, highlighting the importance of crop type and cultivation practices in determining the environmental risks of microplastics in agroecosystems.

The Structure of Left Ventricular Relaxation in Case of Ventriculography.

To study the relaxation structure of the left ventricle (LV) in patients who underwent ventriculography. LV ventriculography was performed in 37 patients. Before catheterization, echocardiography was performed in each patient. In 6 patients, the LV ejection fraction (EF) was below 40%; these patients with systolic dysfunction were not included in the study. In 31 patients, the LV EF was higher than 50%. In this group, 13 patients had NYHA functional class (FC) 2-3 chronic heart failure (CHF); the rest of the patients had FC 1 CHF. Eighteen of 31 patients had stable ischemic heart disease; 50% of these patients had a history of myocardial infarction; the rest of the patients had hypertension and atrial and ventricular arrhythmias. The dynamics of the LV pressure decrease was analyzed from the moment of the maximum rate of pressure drop, which usually coincides with the closure of the aortic valves. The pressure drop curve was logarithmized with natural logarithms and divided into 4-5 sections with different degrees of curve slope. The relaxation time constant was calculated for each section. Its inverse value characterizes the relaxation time constant (tau). In 31 patients with LV EF 52-60%, three types of the dynamics of the relaxation rate constant were identified during the pressure decrease in the isovolumic phase: in 9 patients, the isovolumic relaxation constant (IRC) steadily increased as the pressure decreased; in 13 patients, it continuously decreased; and in 9 patients, the dynamics of IRC change was intermediate, with an initial increase followed by a decrease. In diastolic dysfunction, one group of patients had an adaptation type associated with an increase in the LV wall elasticity, while the other group had a different type of adaptation associated with its decrease. Each type has advantages and disadvantages. This is probably due to changes in the structure of the sarcomeric protein connectin (titin).

The high dimensional Fisher-KPP nonlocal diffusion equation with free boundary and radial symmetry, part 2: Sharp estimates

This is the second part of a two-part series devoted to an in depth understanding of the dynamical behaviour of the radially symmetric Fisher-KPP nonlocal diffusion equation with free boundary |x|=h(t). In Part 1 [19], we have shown that the long-time dynamics of this problem is characterised by a spreading-vanishing dichotomy, and there exists a threshold condition on the diffusion kernel J(|x|) such that the spreading speed is ∞ when this condition is not satisfied, and when it is satisfied, the finite spreading speed c0 is determined by an associated semi-wave problem established in [15]. In Part 2 here, we obtain more precise description of the spreading profile by focusing on some natural classes of kernel functions, including those satisfying J(|x|)∼|x|−β for |x|≫1 in RN. Our results for such kernels reveal a striking difference of behaviour from the pattern exhibited in the one dimension case [18] when β crosses the value N+2. More precisely, (a) when β∈(N,N+1], we show that for t≫1, h(t)∼t1/(β−N) if β∈(N,N+1), and h(t)∼tln⁡t if β=N+1, which is of the same pattern as in dimension one, namely we recover the result in [18] by letting N=1 in the above statements; (b) when β∈(N+1,N+2], the front has a finite spreading speed c0=c0(β) in the sense that limt→∞⁡h(t)/t=c0, and our results here on the order of shift c0t−h(t) are again of the same pattern as in dimension one; (c) when β>N+2, the front still has a finite spreading speed c0, but a significant change happens to the order of shift c0t−h(t) between N≥2 and N=1: for t≫1, c0t−h(t)∼ln⁡t when N≥2, but c0t−h(t)∼1 when N=1.

Utility-implied term structures of equity risk premia

The fundamental asset pricing problem is extended to the frequency domain for commonly used utility functional forms. For each class of utility functions, closed-form solutions are presented for the term structure of the equity risk premium. The term structure is flat for time separable one-period utility and uncorrelated external habit formation utility, downward sloping for internal habit formation utility, upward sloping for time preference (recursive) utility, and can be upward sloping, downward sloping, or flat for production-based utility. These results suggest how observed risk premium term structures can be mapped to linear time series models consistent with utility preference classes.

An approach to generalized (η1,η2)-convex functions via local fractional calculus and some applications

The purpose of this paper is to study a generalization of [Formula: see text]-convex functions using the local fractional calculus developed by Yang [Advanced Local Fractional Calculus and its Applications (World Science Publisher, New York, 2012)], namely generalized [Formula: see text]-convex functions. Among other results, we obtain some Fejér-type inequalities for this class of functions. As applications, we present some inequalities with generalized probability density functions and generalized special means.

On Gabor frames generated by B-splines, totally positive functions, and Hermite functions

The frame set of a window ϕ∈L2(R) is the subset of all lattice parameters (α,β)∈R+2 such that G(ϕ,α,β)={e2πiβm⋅ϕ(⋅−αk):k,m∈Z} forms a frame for L2(R). In this paper, we investigate the frame set of B-splines, totally positive functions, and Hermite functions. We derive a sufficient condition for Gabor frames using the connection between sampling theory in shift-invariant spaces and Gabor analysis. As a consequence, we obtain a new frame region belonging to the frame set of B-splines and Hermite functions. For a class of functions that includes certain totally positive functions, we prove that for any choice of lattice parameters α,β>0 with αβ<1, there exists a γ>0 depending on αβ such that G(ϕ(γ⋅),α,β) forms a frame for L2(R). Our results give explicit frame bounds.

To the question of thrombotic and hemorrhagic complications in patients with COVID-19

COVID-19 is characterized by various adverse consequences and complications, the prevention of which affects the outcome of the disease. Aim of the study was to investigate the thrombohemorrhagic events of COVID-19 infection. Material and methods. This study involved 403 patients with novel coronavirus infection; the patients were divided into 2 groups: 75 with COVID-19 complications and 328 patients without complications. Metabolic disorders, features of lung damage, comorbidity, signs of inflammation and coagulation, treatment outcomes, peculiarities of thrombotic events and hemorrhages development were studied. Results and its discussion. Thrombohemorrhagic complications of COVID-19 occurred mostly in patients with angina pectoris, coronary artery sclerosis and chronic heart failure of functional class II–III, as well as decompensated diabetes mellitus and obesity. These coronavirus infection effects are often accompanied by an increase in content of inflammatory markers such as CRP and ferritin, as well as of hypercoagulability (D-dimers). Conclusions. Manifestations of inflammatory coagulopathy in patients infected by COVID-19 increases risk of thrombohemorrhagic complications.

Epidemiology of supplemental oxygen in patients with pulmonary hypertension.

Patients with pulmonary hypertension (PH) may present with hypoxaemia at rest or during daily activities. There is no epidemiological data on the prescription of long-term oxygen therapy (LTOT) in patients with PH. The study sought to analyse the prevalence and incidence of LTOT prescription among patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) in Spain and to determine predictors for this prescription. A retrospective analysis was performed from the Spanish Registry of Pulmonary Arterial Hypertension (REHAP). Collected data included demographics and anthropometric measurements, functional class (FC), arterial blood gases, pulmonary function tests, haemodynamic measurements, six-minute walking distance (6MWD) and LTOT prescription. In addition, we assessed the prevalence and incidence of LTOT prescription by PH group and subtype and potential predictors for LTOT initiation in the first 5 years after diagnosis. We analysed 4533 patients (69.9% PAH and 30.1% CTEPH), mostly female (64.5%), with a mean age of 53.0 ± 18.3 years. The prevalence of LTOT was 19.3% for all patients. The incidence of LTOT prescriptions decreased from 5.6% to 1.6% between 2010 and 2019, respectively. Predictors for LTOT prescription, excluding those that represent the indication for oxygen therapy were: FC (HR: 1.813), 6MWD (HR: 1.002), mean pulmonary arterial pressure (mPAP) (HR: 1.014), cardiac index (CI) (HR: 1.253), pulmonary vascular resistance (PVR) (HR: 1.023) and diffusing capacity of carbon monoxide (DLCO) (HR: 1.294). The prevalence of LTOT in PAH and CTEPH patients is close to 20%. FC, 6MWD, mPAP, CI, PVR and DLCO were predictors for LTOT prescription.

Mid-term clinical outcomes and cardiac function in patients receiving cardiac contractility modulation.

To describe the mid-term clinical and functional cardiac contractility modulation therapy (CCM) recipients in an urban population with heart failure. CCM is a non-excitatory electrical therapy for patients with systolic heart failure with NYHA class III symptoms and ejection fraction (EF) 25-45%. How CCM affects a broad range of clinical measures, including diastolic dysfunction (DD) and weight change, is unexplored. We reviewed 31 consecutive patients at our center who underwent CCM implant. NYHA class, hospitalizations, ejection fraction (EF), diastolic function, and weight were compared pre- and post-CCM implant. Mean age and follow-up time was 63 ± 10years and 1.4 ± 0.8years, respectively. Mean NYHA class improved by 0.97 functional classes (p < 0.001), and improvement occurred in 68% of patients. Mean annualized hospitalizations improved (0.8 ± 0.8 vs. 0.4 ± 1.0 hospitalizations/year, p = 0.048), and after exclusion of a single outlier, change in annualized days hospitalized also improved (total cohort 3.8 ± 4.7 vs. 3.7 ± 14.8days/year; p = 0.96; after exclusion, 3.8 ± 4.7 vs. 1.1 ± 1.9days/year, p < 0.001). Mean EF improved by 8% (p = 0.002), and among those with DD pre-CCM, mean DD improvement was 0.8 "grades" (p < 0.001). Mean weight change was 8.5 pounds lost, amounting to 4% of body weight (p = 0.002, p = 0.002, respectively), with 77% of patients having lost weight after CCM. Five patients (16%) experienced procedural complications; incidence skewed toward early implants. In an observational cohort, CCM therapy resulted in improvement in NYHA class, hospitalizations, systolic and diastolic function, and weight.

Risk stratification and treatment goals in pulmonary arterial hypertension.

Risk stratification has gained an increasing role in predicting outcomes and guiding the treatment of patients with pulmonary arterial hypertension (PAH). The most predictive prognostic factors are three noninvasive parameters (World Health Organization functional class, 6-min walk distance and natriuretic peptides) that are included in all currently validated risk stratification tools. However, suffering from limitations mainly related to reduced specificity of PAH severity, these variables may not always be adequate in isolation for guiding individualised treatment decisions. Moreover, with effective combination treatment regimens and emerging PAH therapies, markers associated with pulmonary vascular remodelling are expected to become of increasing relevance in guiding the treatment of patients with PAH. While reaching a low mortality risk, assessed with a validated risk tool, remains an important treatment goal, preliminary data suggest that invasive haemodynamics and cardiac imaging may add incremental value in guiding treatment decisions.

Evaluating Mitral TEER in the Management of Moderate Secondary Mitral Regurgitation Among HeartFailurePatients.

Moderate secondary mitral regurgitation (SMR) represents a subgroup of heart failure (HF) patients with treatment restricted to medical therapy. Outcomes in patients with moderate SMR treated with mitral transcatheter edge-to-edge repair (M-TEER) are less well known. The aim of this study was to assess the safety and effectiveness of M-TEER in subjects with moderate SMR using the EXPANDed studies. One-year outcomes in subjects from the EXPANDed studies (EXPAND [A Contemporary, Prospective Study Evaluating Real-world Experience of Performance and Safety for the Next Generation of MitraClip Devices] and EXPAND G4 [A Post-Market Study Assessment of the Safety and Performance of the MitraClip G4 System] MitraClip studies) with baseline moderate SMR (2+), per echocardiographic core laboratory (ECL) assessment, were compared with subjects with baseline severe SMR (≥3+). There were 335 subjects with moderate SMR and 525 with severe SMR at baseline per ECL review. Baseline characteristics were similar between the 2 subgroups. After treatment with M-TEER, significant MR reduction was achieved in both groups. Significant left ventricular (LV) reverse remodeling was observed through 1 year, with a >20mL decrease in LV end-diastolic and end-systolic volumes on average in the moderate SMR group. Significant 1-year improvements in NYHA functional class (>78% NYHA functional class I or II) and quality of life (>20 points on the Kansas City Cardiomyopathy Questionnaire-Overall Summary) were observed in subjects with moderate SMR. Similarly, low rates of major adverse events, all-cause mortality, and HF hospitalizations were observed between the 2 subgroups through 1 year. In the EXPANDed studies, subjects with moderate SMR treated with M-TEER had improvements similar to subjects with severe SMR in quality of life and positive LV remodeling at 1 year. Future studies are needed to evaluate if M-TEER would be beneficial for HF patients with moderate SMR.

Positivity-Preserving Rational Cubic Fractal Interpolation Function Together with Its Zipper Form

In this paper, a novel class of rational cubic fractal interpolation function (RCFIF) has been proposed, which is characterized by one shape parameter and a linear denominator. In interpolation for shape preservation, the proposed rational cubic fractal interpolation function provides a simple but effective approach. The nature of shape preservation of the proposed rational cubic fractal interpolation function makes them valuable in the field of data visualization, as it is crucial to maintain the original data shape in data visualization. Furthermore, we discussed the upper bound of error and explored the mathematical framework to ensure the convergence of RCFIF. Shape parameters and scaling factors are constraints to obtain the desired shape-preserving properties. We further generalized the proposed RCFIF by introducing the concept of signature, giving its construction in the form of a zipper-rational cubic fractal interpolation function (ZRCFIF). The positivity conditions for the rational cubic fractal interpolation function and zipper-rational cubic fractal interpolation function are found, which required a detailed analysis of the conditions where constraints on shape parameters and scaling factor lead to the desired shape-preserving properties. In the field of shape preservation, the proposed rational cubic fractal interpolation function and zipper fractal interpolation function both represent significant advancement by offering a strong tool for data visualization.

Characteristics, Treatment, and Prognosis of Heart Failure Patients with Chronic Obstructive Pulmonary Disease in the Colombian Heart Failure Registry (RECOLFACA)

The impact of chronic obstructive pulmonary disease (COPD) on heart failure (HF) has yet to be well assessed in the Latin American population. This study aimed to analyze the impact of COPD on HF patients from the Colombian Heart Failure Registry (RECOLFACA). The primary outcome was all-cause mortality. A Cox proportional-hazards regression model was used to assess the impact of COPD on mortality. From the total of 2528 patients in the registry, 2514 patients had information regarding COPD diagnosis. COPD diagnosis was associated with a worse functional class and higher use of diuretics than non-COPD patients (p &lt; 0.001). Patients with this comorbidity had a significantly better ejection fraction (median ejection fraction 35% vs. 32% in non-COPD patients; p = 0.004), with a higher occurrence of HF with preserved ejection fraction (HFpEF) in the COPD group (p = 0.000). Finally, patients with COPD had a significantly higher risk of mortality in the multivariate regression model (HR 1.47; 95% CI 1.02, 2.11). COPD is a prevalent comorbidity among patients with HF in Colombia, showing a different clinical profile and a worse functional class than patients without this condition. Patients with COPD and HFpEF have a high mortality risk according to our results.

On the Value of Information Across Decision Problems

The value of information is an important concept in decision analysis that has been quantified as the buying price (BPI) for the information and the expected utility increase (EUI) obtainable by using the information. These two measures rank information sources identically in a scalar-valued decision problem only when the utility function is linear or exponential. In contrast, this paper focuses on the value of information across scalar-valued decision problems sharing the same utility function such as different divisions within an organization exploring various information sources for their decisions using the same organizational utility function. In this context, it still makes sense to ask which sources are more informative. We show that BPI and EUI rank information sources identically in this context only when the utility function is linear. However, if the certainty equivalent increase is used instead of EUI, then identical ranking with BPI across problems is maintained for the broader class of linear or exponential utility functions. We discuss the importance of these results for distributed decision-making settings, where different departments within an organization may calculate the value of information separately. Our results advise against using EUI to measure information value in this context when risk attitude is important.

Impact of cardiac structure and function on exercise intolerance in Chagas cardiomyopathy: Insights from CPET and echocardiography

Introduction: Chronic Chagas cardiomyopathy (CCC), the most severe clinical condition of Chagas disease, often leads to a reduction in functional capacity and the appearance of symptoms such as fatigue and dyspnea on exertion. However, its determinant factors remain unclear. We aimed to evaluate the peak oxygen consumption (VO2peak) in patients with CCC and identify its determining factors. Methods: An observational study with 97 CCC patients was conducted. Patients underwent clinical examination, cardiopulmonary exercise test (CPET), and echocardiography as part of the standard clinical evaluation. Multivariate linear regression was used to identify independent clinical and echocardiographic predictors of VO2peak and percentage of predicted VO2. Results: Mean age of study patients was 55.9 ± 13.4 years, median left ventricle ejection fraction (LVEF) was 40 (26–61.5) % and median VO2peak was 16.1 (12.1–20.8) ml/Kg/min. 36 patients presented preserved LVEF and 61 presented reduced LVEF. There were significant differences in almost all CPET variables (p < 0.05) between these two groups. VO2peak was associated with age, male sex, NYHA functional class, LVEF, left atrium diameter, LV diastolic diameter, E wave, LV mass index, and pulmonary artery systolic pressure (PASP). Age, male sex, LVEF, and E wave remained independently associated with VO2peak in the multivariate analysis (R2 = 0.69), furthermore, only LVEF and E wave were associated with the predicted VO2 percentage (R2 = 0.53). Conclusion: In patients with CCC, disease severity, male sex, LV systolic and diastolic function influence the functional capacity.

Transthyretin cardiac amyloid: Broad heart failure phenotypic spectrum and implications for diagnosis.

Transthyretin cardiac amyloidosis (ATTR-CA) is most often associated with heart failure with preserved ejection fraction (HFpEF). However, patients may present with impaired systolic function at the time of diagnosis, which has not been widely investigated. We sought to explore the prevalence of various heart failure (HF) phenotypes and their associated clinical characteristics at the time of ATTR-CA diagnosis. We performed a single-centre retrospective cohort study of consecutive patients with ATTR-CA evaluated between February 2016 and December 2022. Data on patient demographics, comorbidities, imaging and laboratory findings were compared across HF phenotypes (age: 78.1±8.6years, with 91.1% male). A total of 21.6% (n=46) presented with heart failure with reduced ejection fraction (HFrEF), 17.8% (n=38) with heart failure with mildly reduced ejection fraction (HFmrEF) and 60.6% (n=129) with HFpEF at the time of diagnosis with ATTR-CA. Those presenting with HFrEF or HFmrEF were more likely to be African American and had significantly worse New York Heart Association (NYHA) functional class, higher N-terminal pro-brain natriuretic peptide (NT-proBNP) and higher serum creatinine levels as compared with those with HFpEF. Although ATTR-CA is traditionally thought to be seen primarily among patients with HFpEF, our data suggest that ATTR-CA has a higher prevalence among patients with HFrEF, which underscores the importance of heightened clinical suspicion regardless of ejection fraction when considering ATTR-CA. Furthermore, although comorbidities are similar, patients with HFmrEF and HFrEF had a worse symptom burden.

TSLiNGAM: DirectLiNGAM under heavy tails

One of the established approaches to causal discovery consists of combining directed acyclic graphs (DAGs) with structural causal models (SCMs) to describe the functional dependencies of effects on their causes. Possible identifiability of SCMs given data depends on assumptions made on the noise variables and the functional classes in the SCM. For instance, in the LiNGAM model, the functional class is restricted to linear functions and the disturbances have to be non-Gaussian. In this work, we propose TSLiNGAM, a new method for identifying the DAG of a causal model based on observational data. TSLiNGAM builds on DirectLiNGAM, a popular algorithm which uses simple OLS regression for identifying causal directions between variables. TSLiNGAM leverages the non-Gaussianity assumption of the error terms in the LiNGAM model to obtain more efficient and robust estimation of the causal structure. TSLiNGAM is justified theoretically and is studied empirically in an extensive simulation study. It performs significantly better on heavy-tailed and skewed data and demonstrates a high small-sample efficiency. In addition, TSLiNGAM also shows better robustness properties as it is more resilient to contamination. Supplementary Materials for this article are available online.