bluuebunny/crossref_metadata_2025 huggingface dataset:
Transoesophageal echocardiography findings in young patients with cryptogenic ischemic stroke
Authors: Hutyra M , Sanak D , Kral M , Dornak T , Precek J , Hudec S , Navratil K , Kocianova E , Koubek F , Kanovsky P , Taborsky M
Published: October 2022

Background and purpose

The cause of ischemic stroke (IS) remains often unclear in young patients. Relevant structural heart abnormities with known embolic potential may represent cause of IS also in young population. The use of transoesophageal echocardiography (TEE) allows reliable detection of most relevant structural pathologies. The aim was to assess frequency and spectrum of relevant cardiac abnormities in young IS patients.

Subjects and methods

The study set consisted of young acute IS patients <50 years enrolled in the prospective HISTORY (Heart and Ischemic STrOke Relationship studY) study, registered on ClinicalTrials.gov NCT01541163). In all patients, the brain ischemia was confirmed on CT or MRI. Admission ECG, serum specific cardiac markers, TEE, 24-hour and 3-week ECG-Holter were performed in all patients.

Results

Out of 1284 patients enrolled in the HISTORY study, 135 (73 males, mean age 40.2±8.1 years) were <40 years. In total, the relevant TEE abnormities were present in 47 (35%) of these patients. Patent foramen ovale (PFO) with evident left to right shunt was detected in 38 (28%) patients, with significant right to left shunt in 25 (19%) patients, and other atrial septal defect with clinically significant bidirectional flow in 4 (3%) patients. Significant valvular heart disease was present in 2 (1%) patients (1 bicuspid aortic valve with moderate aortic regurgitation, 1 chronic severe mitral regurgitation), and 4 (3%) patients severe left ventricular systolic dysfunction (left ventricular ejection fraction ≤35%) due to idiopathic dilated cardiomyopathy. Left atrial myxoma was detected in one patient.

Conclusion

The relevant structural abnormities with embolic potential were detected using TEE in 35% of young IS patients. Routine use of TEE to elucidate the causes of stroke, has a role especially in young patients who present with cryptogenic stroke and no cardiovascular risk factors, as well as in the setting of a PFO associated with a deep venous thrombosis.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): IGA LF UP, MH CZ - DRO
QTc interval in anorexia nervosa: a systematic review and meta-analysis
Authors: Rastogi J , Ho J , Rastogi J , Lazari J , Jageer P , Davis S , Kirresh A , Yiu J , Jain D , Ahmad M , Providencia R , Bray J
Published: October 2022

Background

Patients with anorexia nervosa (AN) are at higher risk of sudden cardiac death. Although the underlying aetiology for this association remains unclear. It may be related to prolongation of the QT interval, which can degenerate into fatal ventricular arrhythmias. However, the presence of prolonged heart rate-corrected QT interval (QTc) in AN remains controversial, and two previous meta-analyses on AN and QTc showed contradictory findings [1,2].

Purpose

In this systematic review and meta-analysis, we aimed to evaluate if AN was associated with changes in the QTc interval and dispersion.

Methods

MEDLINE, EMBASE and COCHRANE databases were systematically searched from inception to January 2021. Random-effects meta-analysis and meta-regression were used. The inclusion criteria were (i) confirmed diagnosis of AN, (ii) measurement of QTc on electrocardiogram and (iii) peer-reviewed articles. The primary endpoint of the study was the duration of the QTc interval calculated using the Bazett (QTcB), Hodges (QTcH), Fridericia (QTcF) and Framingham (QTcFr) formulae. The secondary endpoints were QT dispersion (QTd) and QTc dispersion (QTcd).

Results

The 25 eligible studies included 5687 patients (1862 AN, 3825 control) (Figure 1: PRISMA diagram). The majority of patients were female (96.3%) with a mean age between 14.3 to 31.0 years and mean duration of disease ranging from 9.1 to 129.6 months. The mean BMI ranged from 13.7 to 18.5 kg/m2. Pooled analysis did not show significant prolongation between AN versus control in QTcB (mean difference (MD) MD 4.9ms, 95% CI −3.2, 13.1ms, p=0.23; I2=95%; n=24/25 studies; Figure 2A), QTcH (MD 1.3ms, 95% CI −8.5, 11.2ms, p=0.79; I2=71%; n=3/25 studies), and QTcF (MD 3.1ms, 95% CI −21.6, 27.7ms, p=0.81; I2=97%; n=3/25 studies). Only two studies reporting QTcFr showed a significant prolongation between AN and control (MD 15.9ms, 95% CI 0.0, 31.8ms, p=0.05, I2=65%; n=2/25 studies; Figure 2B). However, QTd and QTcd were significantly greater in AN than control (MD 21.3ms, 95% CI 10.4, 32.3ms, p=0.0001, I2=94%; Figure 2C and MD 16.9ms, 95% CI 4.5, 29.3ms, p=0.007 I2=93%; Figure 2D, respectively).

Conclusion

To the best of our knowledge, this is the largest meta-analysis of QTc in AN and the first meta-analysis exploring the significance of QTd and QTcd in AN. AN was not found to be associated with prolongation of QTc calculated using the Bazett, Fridericia and Hodges formulae. However, an association of AN with prolonged QTc was observed in the studies using the Framingham formula. More pronounced dispersion (QTd and QTcd) was also observed in patients with AN.

Funding Acknowledgement

Type of funding sources: None.
Automated right ventricular strain by speckle tracking echocardiography in patients with systemic scleroderma
Authors: Tsoukas A , Koutsogiannaki E , Giannakopoulou I , Gioti O , Iliopoulos D , Saad R , Chalkitis V , Peteinaki A , Karapedi E , Papaioannou N
Published: October 2022

Introduction

In patients with scleroderma the morphological remodeling and alteration of right ventricular (RV) function begins even before the setting of pulmonary artery hypertension (PAH). These alterations are associated with worse outcomes and high mortality.

Purpose

Early detection of RV dysfunction is possible using advanced imaging techniques and can lead to specific therapeutic measures before installation of PAH. Purpose of this study is to evaluate new indices, based on speckle tracking technology, for identification of subclinical RV systolic failure.

Methods

Twenty-five (25) scleroderma patients without any signs or symptoms of PAH and twenty-five (25) healthy subjects were included in the present study. Two-dimensional echocardiography (2DE) and two-dimensional speckle-tracking echocardiography (2DSTE) were performed. All the usual 2DE, Doppler and tissue Doppler imaging measurements were obtained for the evaluation of RV function. Moreover, TAPSE, maximum systolic myocardial velocity from TDI of lateral tricuspid valve annulus (SRV), auto RV global longitudinal strain (aRVGLS) and auto RV free wall longitudinal strain (aRVFWLS) by 2DSTE were measured. aRVGLS is a new index, with appropriate RV function echo logistics in new technology echo systems, independent from known manual measurements.

Results

In scleroderma patients significantly higher systolic pulmonary artery pressure was recorded, although it remained within normal limits in both groups. Scleroderma patients had significant decreased RV systolic function with significantly lower TAPSE and SRV. Both aRVGLS and aRVFWLS were also significantly lower in scleroderma patients compared to the control group. aRVGLS was the best predictor of early RV systolic impairment in patients with scleroderma.

Conclusions

Scleroderma is a severe systematic disease associated with high mortality rates. RV remodeling, dysfunction, and progressive pulmonary artery hypertension are among the most important internal organ manifestations of this disease. Early detection of RV dysfunction is possible by 2DSTE, and may be helpful to guide further therapy in these patients.

Funding Acknowledgement

Type of funding sources: None.
Association between cumulated hydroxychloroquine in systemic lupus erythematosus and development of cardiac conduction alterations
Authors: Zubiaur Zamacola J , Herrero Morant A , Margarida De Castro A , Perez Barquin R , Blanco Alonso R , Gonzalez-Gay M A
Published: October 2022

Background/Introduction

Hydroxychloroquine (HCQ) is a widely used drug in Systemic Lupus Erythematosus (SLE). It may cause cardiac alterations which includes short term arrhythmic events (via QT interval prolongation) and medium-late term dose dependent cardiomyopathy1. The few research articles published on the medium-late term effects of HCQ in cardiac conduction disorder do not show relevant alterations.

Purpose

To assess the effect of HCQ in cardiac conduction in a consecutive SLE population.

Methods

Observational, single University hospital study of all consecutive SLE patients with an electrocardiogram (EKG) at HCQ onset and at least one EKG in follow-up, with a period of at least 3 months on HCQ treatment was performed. We assessed conduction alteration by electrocardiogram (EKG), defined as any degree of atrio-ventricular block or bundle branch block. The EKGs were gathered from the clinical history and interpreted at the beginning of the treatment and during the 15.2 years (CI95% 13.24–17.16) follow-up period. We defined cumulated HCQ (cHCQ) as the multiple of the mean annual dose of the sample.

Results

We studied 109 (96 women/ 13 men) SLE patients with a mean (±.SD) age of 61 ±. 2.78 years. A statistically significant association was observed between the cHCQ, and the development of cardiac conduction alterations [OR 1.1 CI95% 1.02–1.19; p=0.011] (Table & Figure). A total of 8 covariates were included. Among them, those that had the greatest influence on the development of the primary event were previous conduction alterations [OR 4.15 CI95% 6.39–624.54; p<0.01]; valvular heart disease [OR 7.15 CI95% 1.31–38.91; p=0.023] and age [OR 1.07 95% CI 1.0–1.14; p=0.04] (Table). There was no statistical association between the cHCQ and atrio-ventricular block.

Conclusion

According to our study, it seems to be an association between the cHCQ and development of cardiac conduction alterations regardless of other variables evaluated. Wider longitudinal studies are required with a protocolized EKG performance in successive visits to further analyze this association.

Funding Acknowledgement

Type of funding sources: None.
Global and regional left ventricular deformation evaluation with feature tracking in transthyretin cardiac amyloidosis. Comparison with echocardiographic findings
Authors: Bastidas Plaza D , Pozo Osinalde E , Islas F , Perez De Isla L , Marcos-Alberca P , Hernandez P , Martin-Lores I , Luaces Mendez M , Gomez De Diego J J , Bustos A , Perez-Villacastin J , De Agustin J A
Published: October 2022

Background

Diagnosis of cardiac amyloidosis (CA) is basically based on imaging techniques. Transthoracic echocardiography (TTE) is crucial to raise suspicion of this disease through detection of the classical features. An specific left ventricular (LV) deformation pattern with apical sparing (“cherry on top”) has been described on speckle tracking (ST) TTE. However, there is no data regarding the role of the LV global and regional analysis with the new tool feature tracking (FT) of cardiac magnetic resonance (CMR) in CA.

Purpose

Our aim is to analyze the concordance of LV deformation between ST-TTE and FT-CMR.

Methods

Consecutive patients with definitive diagnosis of transthyretin (TTR) CA, based on DPD scintigraphy, and imaging evaluation with TTE and CMR were retrospectively included. LV volumes and ejection were calculated from both TTE and CMR following the ongoing recommendations. Global and segmental longitudinal strain values were obtained from apical 2-, 3- and 4-chambers projections on TTE, while the same parameters were calculated on the same cine views of CMR using a dedicated software of FT analysis. Student t-test was used to compared mean measurements derived from both imaging techniques. Apical index was calculated as the ratio between apical and basal-mid longitudinal values. Moreover, agreement was established using Passing-Bablok regression analysis.

Results

27 patients (80 years-old, 88% men) with definitive diagnosis of TTR CA from our tertiary hospital were included. Regarding echocardiographic findings, 80% showed concentric LV hypertrophy with low normal ejection fraction in the majority (52±10%). When longitudinal LV strain parameters were compared (Table 1), no differences were noted in global and apical values whereas basal and mid measurements were higher from CRM resulting in different apical indexes. Although 42% showed a typical “cherry on top” pattern in ST analysis, in only 18% of the FT apical sparing was detected. Consistently, decremental pattern was observed in 60% of TTE and in 20% of CMR. Concordance analysis with Passing-Bablok showed no constant or proportional differences, meaning both techniques were comparable.

Conclusions

Among patients with TTR CA there were no differences in global longitudinal LV strain analysis between ST-TTE and FT-CMR. Nevertheless, discordance in regional parameters resulted in a less frequent detection of apical sparing in CMR.

Funding Acknowledgement

Type of funding sources: None.
Relationship between proprotein convertase subtilisin/kexin type 9 (PCSK9) and thrombotic events in primary antiphospholipid syndrome. The multicenter ATHERO-APS study
Authors: Bucci T , Ames P R J , Cammisotto V , Bartimoccia S , Triggiani M , Parente R , Ciampa A , Pignatelli P , Carnevale R , Pastori D
Published: October 2022

Background

The proprotein convertase subtilisin/kexin type 9 (PCSK9) is a novel cardiovascular risk factor. Levels of PCSK9 in thrombotic primary antiphospholipid syndrome (PAPS) have never been investigated.

Methods

Cross sectional comparison of baseline characteristics of 91 PAPS patients enrolled in the multicenter ATHERO-APS cohort study. PCSK9 levels were categorized into tertiles and the association with arterial and recurrent thrombosis were assessed by univariable and multivariable regression analysis.

Results

Median age was 51 years and 71.4% (n=65) were women. Overall, 33% (n=30) experienced an arterial event while 31% (n=28) had recurrent thrombotic events. Median PCSK9 levels were 1243 (1100–1650) pg/ml. Patients in the third PCSK9 tertile (>1458 pg/ml) showed a higher prevalence of dyslipidemia, lupus anticoagulant positivity and a history of previous arterial and recurrent thrombosis than patients in the first and second tertile. PCSK9 levels were higher in arterial than venous thrombosis (1502 vs. 1180 pg/ml, p=0.002), and in patients with recurrent vs isolated thrombosis (1680 vs. 1150 pg/m, p<0.001). High plasma PCSK9 levels were associated with a 4-fold increase risk for arterial events and with a 10-fold increase risk for recurrent thrombosis after adjustment for confounding factors.

Conclusion

These preliminary data suggest that in PAPS, PCSK9 levels are associated with arterial and recurrent thrombosis. Its role as a possible therapeutic target in PAPS needs further studies.

Funding Acknowledgement

Type of funding sources: None.
Risk stratification for systemic lupus erythematosus associated pulmonary hypertension by simplified ESC/ERS guidelines: data from SOPHIE registry
Authors: Zhou M , Siu C W
Published: October 2022

Background

The ESC/ERS guideline has established a diagnostic algorithm for pulmonary hypertension (PH) based on the peak velocity of tricuspid regurgitation, clinical history of left heart disease, chest radiography, and other chest radiological techniques. Unfortunately, due to the medical resource limitations, not all patients can receive the comprehensive inspections listed above.

Purpose

The purpose of the study was to sort out the practical predicting factors and evaluate the efficacy of the simplified diagnostic algorithm derived from the 2015 ESC/ERS clinical guidelines.

Methods

According to the ESC/ERS guideline, patients in the intermediate or high echocardiographic probability of PH group and further satisfied the following risk stratification criteria (anti-RNP (+), Raynaud phenomenon (+), 6MWD <440 meters, and SVR >1500 wood) were considered to have the intermediate (IR), and high risk (HR) of PH. Patients with a low echocardiographic probability of PH and those with intermediate or high probability of PH without satisfied the risk stratification algorithm were categorized into the low risk (LR) of the PH group.

Results

1005 patients were categorized into the LR group, 30 patients in the IR group, and 19 in the HR group. Precisely, patients in the LR group were relatively younger (49.9±0.4) than that of the IR group (57.8±2.3, p=0.001) and the HR group (56.0±3.0, p=0.035). Raynaud phenomenon was occurred more frequently in the IR group (50.0%) or HR group (47.4%) compared to that of the LR group (24.1%). The occurrence of anti-RNP positive was higher in the HR group, taken up for 57.9% compared to 31.5% in the LR group (p=0.013). The incidence of right axis deviation (RAD) was increasing in the IR group (17.2%) and HR group (16.7%) compared to the LR group (3.6%). In addition, patients in IR and HR group have reduced lung volume parameters, including forced vital capacity (FVC%), forced expiratory volume at the first second (FEV1%), FEV1/FVC ratio, and forced expiratory flow at 50% of forced vital capacity (FEF50%) when compared to the LR group. Multivariate analysis was performed in four different modes to sort out the independent predictors of PH. Anti-RNP (OR=10.5, CI: 1.9, 56.5) and RAD (OR=21.9, CI: 5.2, 92.2) in mode 1, RVH (OR=10.4, CI: 1.9, 56.3) in mode 2, RAD (OR=10.3, CI: 2.0, 50.7) and FEF50% (OR=1.0, CI: 0.90, 0.97) in mode 3, and RVH (OR=56.8, CI: 6.9, 467.5) and FEF50% (OR=1.0, CI: 0.90, 0.97) in mode 4 were identified as the independent predictors of PH for SLE patients.

Conclusions

This registry has provided main clinical characteristics and phenotypes of Hong Kong Chinese patients with SLE and has demonstrated that Anti-RNP, RAD, RVH, or FEF50% was independent predictors of pulmonary hypertension in patients with SLE.

Funding Acknowledgement

Type of funding sources: None.
Biologics improve endothelial, vascular and left ventricular myocardial function in patients with psoriatic arthritis
Authors: Ikonomidis I , Pavlidis G , Katogiannis K , Kapniari I , Theodoropoulos K , Kountouri A , Kostelli G , Tsilivarakis D , Thymis J , Katsimbri P , Parissis J , Filippatos G , Lambadiari V , Papadavid E
Published: October 2022

Background/Introduction

Psoriatic arthritis is characterized by systemic inflammation leading to an increased risk of cardiovascular diseases.

Purpose

We aimed to investigate the effects of biologics on endothelial glycocalyx, vascular and left ventricular (LV) myocardial function in patients with psoriatic arthritis.

Methods

One hundred twenty patients (mean age: 51±11 years) with psoriatic arthritis were randomized to receive biologics [n=60; anti-tumor necrosis factor-α (etanercept, adalimumab, infliximab), anti-interleukin (IL)-12/23 (ustekinumab) or anti-IL-17 (secukinumab)] or nonbiologics (n=60; methotrexate or cyclosporine). At baseline and 4 months post-treatment, we measured: (1) Perfused boundary region (PBR) of the sublingual microvessels with a diameter 5–25μm using Sidestream Dark Field camera (Microscan, Glycocheck). Increased PBR indicates impaired glycocalyx integrity. (2) Pulse wave velocity (PWV - Complior; ALAM Medical), (3) Coronary flow reserve (CFR) in the distal left anterior descending coronary artery, (4) Flow-mediated dilation (FMD) of the brachial artery and (5) LV global longitudinal strain (GLS) using speckle-tracking echocardiography.

Results

Compared with baseline, all patients had reduced PWV (11±2.1 versus 10.3±1.5m/s, p=0.001) and increased FMD (5.45±3.2 versus 9.77±4.7, p=0.004) at 4 months. PBR remained unchanged in both study groups (p>0.05). Compared with nonbiologics, biologics resulted in a greater reduction of PWV (−10% versus −4%) and in a greater increase of CFR (+11% versus −1%), FMD (+102% versus +56%) and GLS (+10% versus −2%) (p>0.05 for all comparisons) 4 months post-treatment. In patients treated with biologics, the percent increase of GLS post-treatment was related with the percent reduction of PWV (r=−0.28, p=0.034) and with the percent increase of FMD (r=0.42, p=0.006).

Conclusion

In psoriasis arthritis, biologics confers a greater improvement of endothelial, vascular and LV myocardial function compared with nonbiologics after 4-month treatment.

Funding Acknowledgement

Type of funding sources: None.
Prevalence of abnormal left ventricular geometry and predictors of left ventricular hypertrophy in patients with rheumatoid arthritis
Authors: Ruangpan K , Nilmoje T , Aiewruengsurat D
Published: October 2022

Background

Rheumatoid arthritis (RA) patients have an excess risk of cardiovascular morbidity and mortality. Left ventricular hypertrophy (LVH) is generally considered a target organ damage of hypertensive patients, but it is an overlooked condition in the RA. In addition, LVH is one-sixth prevalence in RA patients and reflects a greater risk of cardiovascular events.

Purpose

We aimed to study the prevalence of LVH in patients with RA without symptomatic cardiovascular disease and explore the associated factors of LVH.

Methods

A cross-sectional study was conducted among adult RA patients and a retrospectively review of echocardiography from the database in non-RA participants. LVH was defined as LV mass index greater than 115 g/m2 in males or 95 g/m2 in females. The prediction model for LVH was constructed by stepwise logistic regression. The prediction model's performance on the test data is evaluated using receiver operator characteristic (ROC) curves to predict the presence of LVH and optimal cut-off point determined by the Youden index.

Results

This study included 109 RA patients and 119 age- and sex-matched non-RA participants. RA participants showed a significantly greater CV risk factor profile; hypertension, diabetes, and dyslipidemia than non-RA participants. Fifty two of 109 (47.7%) RA patients had abnormal LV geometry; eccentric hypertrophy, concentric remodeling, and concentric hypertrophy were 8/109 (7.3%), 28/109 (25.7%), and 16/109 (14.7%), respectively. The prevalence of LVH in RA patients was comparable to non-RA participants 24/109 (22%) and 28/119 (23.5%), p=0.91, respectively. However, there was significantly higher relative wall thickness in RA than non-RA participants 0.4±0.1 and 0.3±0.1, p<0.001, respectively. The diagnostic performance of the score prediction [(0.025×systolic blood pressure) + (non-steroidal anti-inflammatory drug × (0 or 1)) + (0.141×Troponin T level) ≥3.948] was to predict LVH in RA patients showed 91% sensitivity and 39% specificity (AUC = 0.689, 95% CI 0.564–0.814).

Conclusion

RA was associated with higher abnormal LV geometry compared to the non-RA participant. LVH is not uncommon in RA patients, and we could consider it as a target organ damage despite no obvious cardiovascular risk factors. The risk predictor score may be applied for fundamental screening tool for LVH in RA patients before sending the patients for echocardiography.

Funding Acknowledgement

Type of funding sources: None.
Predictors and clinical consequences of heart damage in CMR in patients after COVID-19
Authors: Chudzik M , Miskowiec D , Kapusta J , Babicki M , Kasprzak J D
Published: October 2022

Methods

Out-hospital clinic patients (pts) recovered from COVID-19 were prospectively recruited and underwent cardiac magnetic resonance (CMR) examination with a protocol including: edema, hyperemia, and necrosis or scar-derived from signal intensity assessment in T2-weighted, early gadolinium enhancement (EGE) and late gadolinium enhancement (LGE) CMR images.

Results

A total of 702 patients (mean age 50±12 years, 62% female) were included. The median (IQR) time interval between COVID-19 diagnosis and CMR was 13 (8–22) weeks. In none pts signs of edema, hyperemia and necrosis derived from signal intensity assessment in T2-weighted and early gadolinium enhancement was found. LGE was found in 152 (22%). LGE+ patients had significantly lower left ventricular (LV) ejection fraction (58.5±7.7 vs 61.1±7.9%, p<0.001) and greater LV end-diastolic (117.0±52.2 vs 103,0±36.3 ml, p=0.023) and end-systolic (50.3±28.0 vs 41.0±17.5 ml, p=0.010) volumes when compared with LGE− patients. In the resting electrocardiogram (ECG) fragmented QRS was observed significantly more frequently (46% vs 25%, p<0.001) in LGE+ group, whereas in 24h Holter ECG neither single premature, nor complex ventricular extrasystole burden did not differ between groups (p>0.05). There were observed no differences between symptoms of COVD-19 and comorbidities between LGE+ and LGE− pts. In the multivariable logistic regression analysis: fragmented QRS [OR and 95% CI: 2.85 (1.93–4.21)] and any ST-T segment deviation in resting ECG [OR: 1.93 (1.15–3.25)] were identified as independent predictors of LGE, even after adjustment for comorbidities and COVID-19 symptoms.

Conclusions

1. In patients with fibrosis after COVID-19 reduced left ventricular ejection fraction and greater volume of the heart was found.

2. Fragmented QRS and ST-T abnormalities were independent predictors for LGE in patients after COVID-19.

Funding Acknowledgement

Type of funding sources: None.
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

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<0.0001) and more likely to be females (95% vs 83%, p<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 <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

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<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

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<0.001). We also observed a positive correlation between galectin-3 and IL-6 (r=0.559, p<0.001), ST2 (r=0.332, p=0.005), SOFA score (r=0.441, p=0.003), von Willebrand factor (r=0.401, p<0.001), plasminogen (r=0.361, p=0.001), antithrombin (r=0.453, p<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

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<0.001, also global work index (GWI) was lower in ALC 1334 (956–1761) mmHg% vs. 1984 (1765–2098) mmHg% respectively, P<0.001. Similarly, global constructive work (GCW) was 1662 (1223–2175) mmHg% in ALC vs. 2249 (2036–2320) mmHg% in CG, P<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

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

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<0.001), LV global longitudinal strain (p<0.001), LAS (p<0.001) and MAPSE (p<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<0.001), 0.67 (p<0.001) and 0.66 (p<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<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

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

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 (>10%), LVEF/RVEF decrease (5%), newly developed LGE on CMR, increase in ventricular ectopy (>100% PVCs/24h if >1000 PVCs/24h), decrease in QRS voltage (>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

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<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<0.001), however, creatinine percent change was significantly smaller in pemafibrate than in bezafibrate (5.72% vs. 15.5%, p<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.