bluuebunny/crossref_metadata_2025_split huggingface dataset:
Takotsubo's cardiomyopathy in patients with pre-existing autoimmune diseases: a national inpatient sample analysis
Authors: Kannayiram S , Velagapudi S , Kang C Y , Sami F L , Romero-Noboa M E , Murthi M , Alsahoury J , Krishnaraju E , Khanal S 
Published: October 2022

Abstract

Background
Recent research has suggested a potential role of autoimmunity and inflammation in Takotsubo's cardiomyopathy (TC) [1]. There have been few reports of TC occurring in patients with pre-existing autoimmune diseases (AID). It has also been hypothesised that the low prevalence of TC in patients with AID might be due to attenuating effect on the inflammatory response to catecholamine excess in TC by immunosuppressive medications used in AID patients [2]. On a population-based level, the prevalence of AID in TC patients and its implications remain unknown.

Purpose
Using a large national database, we aimed to describe the prevalence of AID in TC patients and its impact on in-hospital outcomes of TC patients.

Methods
We performed a retrospective analysis using the 2016–2019 National inpatient sample database in the United States, covering over 7 million admissions per year. Using ICD-10 codes, we identified patients with TC and a concomitant diagnosis of any of the AID† depicted in Table 1. We compared TC patients with (AID+) and without AID (AID−) for patient characteristics and in-hospital outcomes. Our primary outcome of interest was mortality. Secondary outcomes are listed in Table 2. Linear regression and multivariate logistic regression analysis were done using STATA 17 to adjust for confounders.

Results
158,230 patients were admitted with TC and of those, 2880 (1.8%) had concomitant AID. Systemic lupus erythematosus (n=1515, 54.1%) was the most common AID followed by Sjogren's syndrome (n=645, 23.02%) Systemic sclerosis (n=440, 14%) and Rheumatoid Arthritis (n=200, 7.1%) in TC population. Compared to TC patients without AID, AID+ patients were relatively younger (mean age of 63 vs 67 years, p&lt;0.0001) and more likely to be females (95% vs 83%, p&lt;0.0001*). 200 (7.1%) and 9459 (6.08%) TC patients with and without AID died during hospitalisation,respectively. TC patients with AID had lower odds of developing acute decompensated heart failure [ADHF] (aOR=0.69 95% CI: 0.56–0.85, p=0.001*) and acute stroke (aOR=0.60, 95% CI: 0.43–0.85, p=0.005*) There was no statistical significance in mortality, rates of acute respiratory failure, cardiogenic shock and healthcare utilisation (Table 2).

Conclusion
Our study notes a substantially higher number of TC patients with pre-existing AID than previously reported in the literature. In addition, these patients have lower odds of developing acute stroke and ADHF, while there was no significant difference for cardiogenic shock and mortality. Further studies are required to decipher the potential link between AID and TC and explore the possible role of immunosuppressants in TC therapy, as suggested in prior studies.
*P-value &lt;0.05 was considered statistically significant. aOR = Adjusted Odds Ratio. †AID included in the study are mentioned in Table 1.

Funding Acknowledgement
Type of funding sources: None.
Parameters of coagulation and platelet hyperreactivity reflect an increased mortality in patients with moderate to severe COVID-19
Authors: Jakobs K , Puccini M , Reinshagen L , Alsheikh A A , Friebel J , Lanmdesser U , Haghikia A , Kraenkel N , Rauch U 
Published: October 2022

Abstract

Background
Hemostasis is dysregulated in patients with moderate-to-severe coronavirus disease 2019 (COVID-19). However, patients with respiratory diseases other than COVID-19 can also show disturbed coagulation reactions during the acute inflammatory process. Parameters of coagulation and platelet function are here compared between patients with upper respiratory infections with and without COVID-19 and are related to the clinical outcome.

Methods
Hospitalized patients with acute respiratory symptoms and with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-positive (COVpos) and SARS-CoV2-negative (COVneg) status were included. We assessed several parameters of coagulation and fibrinolysis as well as adenosine diphosphate (ADP)-, thrombin receptor activator peptide 6 (TRAP)-, and arachidonic acid (AA)-induced platelet reactivity by impedance aggregometry, as well as leukocyte subtype spectrum and platelet-leukocyte aggregates by flow cytometry and inflammatory cytokines by cytometric bead array. The SOFA score was assessed as marker of the clinical outcome.

Results
87 patients were included in the study of which 50 were COVpos and 37 were COVneg. Von Willebrand factor was significantly higher in COVID positive patients compared to the control group (4456,4 mU/ml [2701,4; 9067,0] vs. 2528,0 mU/ml [1301,2; 3693,8], p&lt;0,001). COVID-positive patients exhibited also more tissue plasminogen activator in the circulating blood than COVID-negative patients with an respiratory infection (11,4 mU/ml [7,2; 24,6] vs. 7,3 mU/ml [4,9; 10,5], p=0,001). ADP, TRAP-, and AA-induced platelet reactivity was significantly higher in COVpos than in COVneg patients. The SOFA score was higher in COVpos than in COVneg patients and again higher in deceased COVpos patients than in surviving COVpos. The SOFA score correlated significantly with parameters of coagulation and platelet function. A larger percentage of classical and intermediate monocytes, and of CD4pos T cells (TH) aggregated with platelets in COVpos than in COVneg patients. Interleukin (IL)-1 receptor antagonist (RA) and IL-6 levels were higher in COVpos than in COVneg patients and again higher in deceased COVpos patients than in surviving COVpos. IL-1RA and IL-6 levels correlated with the SOFA score in COVpos but not in COVneg patients, indicating a COVID-19-specific mechanism.

Conclusion
In moderate-to-severe COVID-19, but not in other respiratory diseases, disease severity was associated with parameters of coagulation and platelet function. Dysregulated coagulation and platelet hyperreactivity were associated to a worse clinical outcome in patients with COVID-19, pointing to the importance of antithrombotic therapy for reducing disease severity.

Funding Acknowledgement
Type of funding sources: None.
Galectin-3 as a possible marker for increased thrombogenicity in COVID-19
Authors: Puccini M , Jakobs K , Friebel J , Reinshagen L , Schencke P A , Haghikia A , Landmesser U , Kraenkel N , Rauch U 
Published: October 2022

Abstract

Background
Galectin-3 is a β-galactoside-binding lectin that has been described to be overexpressed in inflammation, atherosclerosis, and in myocardial fibrosis. In COVID-19, galectin-3 has been proposed as an important regulator of the inflammatory response and fibrosis processes. The role of galectin-3 as a platelet activator and thrombosis enhancer has been also recently described. However, the role of galectin-3 in the thrombotic risk in COVID-19 hasn't been studied extensively.

Methods
Patients with moderate to severe COVID-19 were included in the study. Hospitalized patients with acute respiratory diseases without COVID-19 were examined as controls. We compared the levels of galectin-3, soluble ST2, tissue factor and tissue factor activity (TFa) as well as several other markers of increased thrombogenicity in both groups. The correlations between galectin-3 and coagulation as well as inflammation markers were assessed. The SOFA score was used as a marker for the clinical outcome.

Results
93 patients were included into the study of which 56 were SARS-CoV-2 positive (COV+) and 37 were SARS-CoV-2 negative controls (COV−). Galectin-3 levels were higher in the COV+ group (median 7.10 ng/ml [IQR 4.61–9.81] vs. 5.47 ng/ml [3.63–6.66] p=0.016) as well as the TFa (median 334.48 pM [115.19–632.58] vs. 134.02 pM [86.92–206.66]) and the ST2 levels (median 5.49 ng/ml [2.40–9.28] vs. 2.19 ng/ml [0.66–3.91] p&lt;0.001). We also observed a positive correlation between galectin-3 and IL-6 (r=0.559, p&lt;0.001), ST2 (r=0.332, p=0.005), SOFA score (r=0.441, p=0.003), von Willebrand factor (r=0.401, p&lt;0.001), plasminogen (r=0.361, p=0.001), antithrombin (r=0.453, p&lt;0.001), and D-dimer (r=0.377, p=0.001).

Conclusion
In patients with acute respiratory diseases, especially with COVID-19, galectin-3 is a marker for increased hypercoagulability and worse clinical outcome. Galactin-3 might be a useful therapeutic target for patients with COVID-19.

Funding Acknowledgement
Type of funding sources: None.
The impact of chronic alcohol overuse on myocardial work
Authors: Hamala P H , Kasprzak J D K , Wierzbowska-Drabik K W D 
Published: October 2022

Abstract

Backgrounds
The toxic effect of alcohol on myocardial function expressed as myocardial work is not clear. Myocardial work is a novel, based on speckle tracking imagining method that evaluates left ventricle (LV) work estimated by employing blood pressure and LV global longitudinal strain (GLS).

Purpose
We aimed at the evaluation of the impact of chronic alcohol consumption on echocardiographic parameters describing myocardial work.

Methods
A group of alcohol overusing 92 patients (ALC) and age and sex matched abstainers (CG) were compared according to clinical and echocardiographic data. ALC drank at least 10 alcohol units per week (AUW, AU – 10 gram of pure ethanol), median 28 (11–50) AUW whereas CG consumed at most 2 AUW.

Results
The median time of alcohol overuse was 19 (10–28) years. LV systolic function described by ejection fraction (EF) and GLS was decreased, whereas LV mass index (LVMI) was higher in ALC see Table. Right ventricle (RV) function was lowered in ALC when described by free wall RV strain. Global work effectiveness (GWE) amounted 91 (84–93)% in ALC vs. 95 (94–97)% in CG, P&lt;0.001, also global work index (GWI) was lower in ALC 1334 (956–1761) mmHg% vs. 1984 (1765–2098) mmHg% respectively, P&lt;0.001. Similarly, global constructive work (GCW) was 1662 (1223–2175) mmHg% in ALC vs. 2249 (2036–2320) mmHg% in CG, P&lt;0.001, whereas global wasted work (GWW) was higher in ALC, see Table 1. Moreover, we observed significant positive correlation between free time (FT-time between last alcohol ingestion and echocardiography examination) and GWI (rho=0.24, P=0.02) as well as GCW (rho=0.23, P=0.03).

Conclusions
Chronic alcohol overuse was associated with significantly worse LV function expressed by EF, global longitudinal strain as well as myocardial work parameters. Moreover, the improvement of GWI and GCW reflected myocardial function recovery due to abstinence time.

Funding Acknowledgement
Type of funding sources: None.
The prognostic value of myocardial work in patients with chronic alcohol overuse
Authors: Hamala P H , Kasprzak J D K , Wierzbowska-Drabik K W D 
Published: October 2022

Abstract

Backgrounds
Myocardial work is a novel, based on speckle tracking imagining method that evaluates left ventricle (LV) work estimated by employing blood pressure and LV global longitudinal strain (GLS). The data concerning the prognostic value of non-invasive myocardial work (MW) parameters in alcohol overusers (ALC) is insufficient.

Purpose
Evaluation of prognostic value of four main echocardiographic parameters describing MW in ALC patients.

Methods
The clinical and echocardiography data in 92 (79% men, mean age 49±13 years) ALC were collected and mean 28±16 years follow-up was performed. ALC drank at least 10 alcohol units per week (AUW, AU – 10 gram of pure ethanol), median 28 (11–50) AUW. The median time of alcohol overuse was 19 (10–28) years. Composite endpoint (CE) consisted of cardiac related hospitalization or death. At baseline during TTE examination we calculated global work effectiveness (GWE), global work index (GWI), global constructive work (GCW) and global wasted work (GWW).

Results
CE was observed in 16 (17%) individuals. Among work-related four tested parameters only GWI and GCW showed significant predictive value. Sensitivity and specificity of GWI and GCW in CE prediction were respectively 81% and 57% as well as 94% and 46%. Areas under the ROC curves (AUC) for these parameters were respectively: 0.709 for GWI and 0.710 for GCW, p=0.002 for both of them. Cut-off values for CE prediction were for GWI ≤1312 mmHg% and for GCW ≤1862 mmHg%. ROC and Kaplan-Meier curves for GWI and GCW are showed in the Graph 1 and Graph 2.

Conclusions
In chronic alcohol overusers, lowered GWI and GCW showed significant prognostic values for prediction of combined cardiac endpoint in mid – term observation. The predictors of CE were GWI and GCW.

Funding Acknowledgement
Type of funding sources: None.
Prognostic significance of left ventricular functional parameters in relation to infarct location after ST-elevation myocardial infarction
Authors: Tiller C , Holzknecht M , Lechner I , Reindl M , Fink P , Mayr A , Klug G , Brenner C , Bauer A , Metzler B , Reinstadler S J 
Published: October 2022

Abstract

Aims
In survivors of ST-elevation myocardial infarction (STEMI), the impact of infarct location on the prognostic significance of left ventricular functional parameters is not well established. The aim of this study was to investigate the prognostic relevance of left ventricular (LV) functional parameters in relation to infarct location in STEMI patients treated with contemporary primary percutaneous coronary intervention (PCI).

Methods
This observational study analyzed 803 patients with STEMI that underwent a cardiac magnetic resonance imaging scan in median 3 (interquartile range [IQR]: 2–5) days after primary PCI. The following LV functional parameters were evaluated: LV ejection fraction, LV global longitudinal strain, fast manual long-axis strain (LAS) and mitral annular plane systolic excursion (MAPSE). Primary endpoint was the occurrence of major adverse cardiac events (MACE) defined as composite of death, re-infarction and congestive heart failure.

Results
Three hundred and sixty nine patients (46%) had anterior STEMI. These patients had lower LV functional parameters including LV ejection fraction (p&lt;0.001), LV global longitudinal strain (p&lt;0.001), LAS (p&lt;0.001) and MAPSE (p&lt;0.014). MACE was evaluated at a median of 13 (IQR: 12–37) months after STEMI and occurred in 78 patients (10%). In receiver operating curve analysis, the predictive value of LV ejection fraction, LV global longitudinal strain, LAS and MAPSE was 0.59 (p=0.013), 0.64 (p&lt;0.001), 0.67 (p&lt;0.001) and 0.66 (p&lt;0.001), respectively. When divided according to infarct location, MACE occurred in 47 (13%) anterior STEMI patients, and in 31 (7%) non-anterior STEMI patients, respectively. Area under the curve for the prediction of MACE in anterior vs. non-anterior STEMI was 0.59 vs 0.55 for LV ejection fraction, 0.61 vs 0.63 for LV global longitudinal strain, 0.69 vs 0.62 for LAS and both 0.66 for MAPSE. In multivariable analysis, LAS was independently associated with an increased risk of MACE (hazard ratio: 1.20; 95% confidence interval: 1.10–1.30; p&lt;0.001) in anterior STEMI, whereas in non-anterior STEMI, LV global longitudinal strain was an independent predictor of MACE (hazard ratio: 1.22; 95% confidence interval: 1.08–1.38; p=0.002).

Conclusion
Fast manual LAS emerged as independent predictor of MACE in anterior STEMI treated with contemporary primary PCI whereas LV global longitudinal strain was independently associated with MACE in non-anterior STEMI.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Austrian Society of Cardiology
Dapagliflozin improves Myocardial Flow Reserve in patients with Type 2 Diabetes: the DAPAHEART Trial
Authors: D'Amario D , Leccisotti L , Cinti F , Sorice G P , Lorusso M , Guzzardi M A , Mezza T , Cocchi C , Capece U , Indovina L , Ferraro P M , Iozzo P , Giordano A , Giaccari A , Crea F 
Published: October 2022

Abstract

Objective
Cardiovascular (CV) outcome trials have shown that in patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduces CV mortality and admission rates for heart failure (HF). However, the mechanisms behind these benefits are not fully understood. This study was performed to investigate the effects of the SGLT-2i dapagliflozin on whole body insulin sensitivity, myocardial perfusion, and metabolism in patients with T2D without HF.

Research design and methods
This was a single-center, prospective, randomized, double-blind controlled clinical trial including 16 patients with T2D randomized to SGLT-2i dapagliflozin (10 mg) or placebo. Whole body glucose uptake (WBGU) and myocardial glucose uptake (MGU) were measured with PET/CT with FDG during euglycemic hyperinsulinemic clamp. Stress (i.v. adenosine infusion) and resting myocardial blood flow (MBF) and myocardial flow reserve (MFR) were calculated by PET/CT with 13N-ammonia.

Results
16 patients were randomized (8 dapagliflozin; 8 placebo). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). Dapagliflozin significantly improved MFR (2.56±0.26 vs 3.59±0.35) compared with placebo group (2.34±0.21 vs 2.38±0.24; p for interaction =0.001) and was associated to a reduction of resting MBF corrected for cardiac workload (p=0.045). A trend toward an increase in stress MBF was also detected (p=0.058). Moreover, in dapagliflozin group we observed an increase of WBGU of borderline statistical significance (p=0.06) and no effects on MGU (p=0.41).

Conclusions
At the best of our knowledge, our study, for the first time, demonstrated that SGLT-2 inhibition increases MFR in T2D patients. The data presented provide a new potential explanation of cardiovascular benefits with SGLT-2i as they make patients more tolerant to the detrimental impact of obstructive coronary atherosclerosis on MFR.

Funding Acknowledgement
Type of funding sources: None.
The effect of eplerenone on the disease onset and progression of phospholamban cardiomyopathy in presymptomatic mutation carriers: results of the i-PHORECAST trial
Authors: De Brouwer R , Te Rijdt W P , Hoorntje E T , Karper J C , Westenbrink B D , Te Riele A S J M , Van Der Heijden J F , Amin A , Van Tintelen J P , Asselbergs F W , Wilde A A M , De Boer R A , Van Den Berg M P 
Published: October 2022

Abstract

Background
A pathogenic variant in the gene encoding phospholamban (PLN; p.Arg14del) may cause cardiomyopathy, the pathophysiologic hallmark of which is cardiac fibrosis that may cause malignant ventricular arrhythmias and severe heart failure. There is no evidence-based therapy to modify disease progression in presymptomatic pathogenic variant carriers. Eplerenone is a selective mineralocorticoid receptor antagonist with established antifibrotic properties, and may be a potentially interesting treatment in PLN p.Arg14del mutation carriers.

Purpose
To investigate if preventive therapy with eplerenone attenuates disease onset and progression in PLN cardiomyopathy.

Methods
84 presymptomatic PLN p.Arg14del mutation carriers (median age 39 [27–50] years, 44% males) were randomized 1:1 to receive eplerenone (50mg once daily) or no treatment, and endpoints were adjudicated in a blinded fashion (PROBE design). Baseline values were acquired including demographics, cardiac magnetic resonance imaging (CMR) parameters (ventricular volumes, systolic function, late gadolinium enhancement (LGE)), and electrocardiographic parameters (QRS voltages and ventricular ectopy per 24 hour). Subjects were re-evaluated every year and CMR was performed at baseline and after three years. The composite endpoint included LVEDV/RVEDV increase (&gt;10%), LVEF/RVEF decrease (5%), newly developed LGE on CMR, increase in ventricular ectopy (&gt;100% PVCs/24h if &gt;1000 PVCs/24h), decrease in QRS voltage (&gt;25%), non-sustained ventricular tachycardia, symptoms or arrhythmias necessitating treatment, and cardiovascular death.

Results
Two out of 84 subjects (2%) were lost to follow up. 49 out of 82 remaining subjects (60%) reached the composite end point, 25 (60%) in the control group, 24 (60%) in the treatment group (p=0.825). There was no significant difference between the groups when considering the individual end points, see Table 1. Baseline and follow up CMR was performed on 76 subjects, 39 in the control group, 37 in the treatment group. In total there were 10 (13%) cases of newly developed LGE, 6 (18%) in the control group, 4 (12%) in the treatment group (p=0.556), see Figure 1.

Conclusions
Eplerenone did not significantly attenuate disease onset and progression in presymptomatic PLN p.Arg14del mutation carriers. There was no significant difference in new incidence of LGE between the treatment and control groups.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was financially supported by the Netherlands Cardiovascular Research Initiative, an initiative supported by the Dutch Heart Foundation (The Hague, Netherlands).
Efficacy and safety of pemafibrate versus bezafibrate in coronary artery disease patients receiving statin treatment: a randomized, open-label, cross-over study
Authors: Nakamura A , Kagaya Y , Saito H , Kanazawa M , Sato K , Miura M , Kondo M , Endo H 
Published: October 2022

Abstract

Background
Fibrates activate peroxisome proliferator-activated receptor (PPAR)-α which is associated with lipid metabolism. Bezafibrate is a non-selective PPAR-α agonist, whereas pemafibrate has been developed as a higher selective PPAR-α agonist.

Objective
The efficacy and safety of pemafibrate for 24-week in patients with dyslipidemia was examined in comparison with bezafibrate.

Methods
Sixty patients with hypertriglyceridemia (fasting triglyceride (TG) level of ≥150 mg/dL) were treated with pemafibrate of 0.2 mg/day or bezafibrate of 400 mg/day for 24-week in a randomized cross-over study. Percent change from baseline in TG levels was the primary endpoint, and that in HDL-C and apolipoprotein A-I (Apo A-I) levels was the secondary endpoints.

Results
A significantly greater reduction in TG percent change was observed in pemafibrate than in bezafibrate (−46.1% vs. −34.7%, p&lt;0.001). There was no significant difference in HDL-C percent change between pemafibrate and bezafibrate (18.4% vs. 14.0%, p=0.067), whereas Apo A-I percent change was significantly greater in pemafibrate than in bezafibrate (9.2% vs. 5.7%, p=0.018). Pemafibrate and bezafibrate significantly decreased alanine aminotransferase (ALT) and gamma-glutamyltransferase (γ-GT) levels, and pemafibrate showed a greater reduction than bezafibrate (ALT: −21.9% vs. −10.6%, p=0.048; γ-GT: −43.5% vs. −33.1%, p=0.025). Creatinine levels significantly increased in both treatments (both p&lt;0.001), however, creatinine percent change was significantly smaller in pemafibrate than in bezafibrate (5.72% vs. 15.5%, p&lt;0.001). There was no difference in frequency of adverse event (AE) or serious AE between two treatments, but frequency of creatinine elevation (≥0.5 mg/d and/or 25%) was significantly higher in bezafibrate than in pemafibrate (16/60 vs. 3/60, p=0.004).

Conclusion
As compared with bezafibrate, pemafibrate is more effective to reduce TG levels and to elevate Apo A-I levels, and it is safer in terms of liver and renal function.

Funding Acknowledgement
Type of funding sources: None.